Trial Outcomes & Findings for Proton Beam Teletherapy for Post-Hysterectomy Cancers of the Uterus and Cervix (NCT NCT01600040)

NCT ID: NCT01600040

Last Updated: 2024-10-29

Results Overview

In a population of women with cancers of the cervix or endometrium with pathologically proven spread to regional lymph nodes, dose volume histograms (DVH) were compared between scanning proton beam teletherapy, 3-dimensional conformal radiation therapy (3DCRT) and intensity modulated radiation therapy (IMRT). Structure sets contoured for the proton beam therapy delivered on study were used to plan alternative 3DCRT and IMRT plans by the the same medical physics team (3DCRT and IMRT were not used on study; actual dose for proton beam was compared to the doses that would have been delivered for 3DCRT or IMRT.) Median, 25th percentile, and 75th percentile doses are listed below by tissue volume irradiated (mL) or percentage irradiated (%) for each modality. Dose is measured in grays (Gy), which is defined as the absorption of one joule of radiation energy per kilogram of matter.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 22 participants
• Primary outcome timeframe: 5 years
• Results posted on: 2024-10-29

Participant Flow

Participant milestones

Measure	Proton Radiation Therapy This is a single arm study; all participants will receive proton radiation therapy. Proton radiation therapy: 5 days per week (Mon-Fri) for 5-6 weeks
Overall Study STARTED	22
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Proton Radiation Therapy This is a single arm study; all participants will receive proton radiation therapy. Proton radiation therapy: 5 days per week (Mon-Fri) for 5-6 weeks
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Proton Beam Teletherapy for Post-Hysterectomy Cancers of the Uterus and Cervix

Baseline characteristics by cohort

Measure	Proton Radiation Therapy n=21 Participants This is a single arm study; all participants will receive proton radiation therapy. Proton radiation therapy: 5 days per week (Mon-Fri) for 5-6 weeks
Age, Continuous	59.7 years n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 5 years

Population: 22 patients enrolled, 1 of whom withdrew consent prior to study treatment. Remaining 21 patients were included in the final analysis.

In a population of women with cancers of the cervix or endometrium with pathologically proven spread to regional lymph nodes, dose volume histograms (DVH) were compared between scanning proton beam teletherapy, 3-dimensional conformal radiation therapy (3DCRT) and intensity modulated radiation therapy (IMRT). Structure sets contoured for the proton beam therapy delivered on study were used to plan alternative 3DCRT and IMRT plans by the the same medical physics team (3DCRT and IMRT were not used on study; actual dose for proton beam was compared to the doses that would have been delivered for 3DCRT or IMRT.)

Median, 25th percentile, and 75th percentile doses are listed below by tissue volume irradiated (mL) or percentage irradiated (%) for each modality. Dose is measured in grays (Gy), which is defined as the absorption of one joule of radiation energy per kilogram of matter.

Outcome measures

Measure	Proton Radiation Therapy n=21 Participants This is a single arm study; all participants will receive proton radiation therapy. Proton radiation therapy: 5 days per week (Mon-Fri) for 5-6 weeks
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) 3DCRT: Bowel V30 (mL)	819.0 Gy Interval 663.0 to 1316.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) IMRT: Bowel V30 (mL)	818.0 Gy Interval 640.0 to 1085.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) Proton beam: Bowel V30 (mL)	536.0 Gy Interval 488.0 to 644.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) 3DCRT: Bowel V20 (mL)	2076.0 Gy Interval 1404.0 to 2284.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) IMRT: Bowel V20 (mL)	1480.0 Gy Interval 1053.0 to 1915.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) Proton beam: Bowel V20 (mL)	696.0 Gy Interval 622.0 to 833.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) 3DCRT: Bone marrow V20 (%)	78.4 Gy Interval 72.1 to 82.2
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) IMRT: Bone marrow V20 (%)	64.0 Gy Interval 58.8 to 70.2
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) Proton beam: Bone marrow V20 (%)	60.7 Gy Interval 55.8 to 65.1
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) 3DCRT: Bone marrow V10 (%)	85.3 Gy Interval 80.4 to 89.3
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) IMRT: Bone marrow V10 (%)	64.0 Gy Interval 58.8 to 70.2
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) Proton beam: Bone marrow V10 (%)	60.7 Gy Interval 55.8 to 65.1
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) 3DCRT: Kidney V14 (%)	30.8 Gy Interval 7.4 to 47.4
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) IMRT: Kidney V14 (%)	22.1 Gy Interval 6.9 to 28.2
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) Proton beam: Kidney V14 (%)	18.2 Gy Interval 2.7 to 25.2
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) 3DCRT: Bowel V45 (mL)	455.0 Gy Interval 361.0 to 597.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) IMRT: Bowel V45 (mL)	149.0 Gy Interval 112.0 to 269.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) Proton Beam: Bowel V45 (mL)	202.0 Gy Interval 132.0 to 270.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) 3DCRT: Bowel V40 (mL)	639.0 Gy Interval 492.0 to 757.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) IMRT: Bowel V40 (mL)	464.0 Gy Interval 291.0 to 552.0
Dosimetric Comparison of Proton Beam Treatment With 3-dimensional Conformal Radiation Therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT) Proton Beam: Bowel V40 (mL)	395.0 Gy Interval 299.0 to 444.0

PRIMARY outcome

Timeframe: 10 weeks

Population: 22 patients enrolled, 1 of whom discontinued prior to study treatment. The remaining 21 patients were analyzed.

Acute radiation side effects were prospectively assessed. Below are the treatment-related acute toxicities (adverse events possibly, probably, or definitely related to protocol treatment that started within 4 weeks of treatment completion) that occurred on study, along with the number of participants who experienced each event at a given severity (Grade 1/mild, Grade 2/moderate, Grade 3/severe) according to the CTCAE v 4.02 (Common terminology criteria for adverse events).

Outcome measures

Measure	Proton Radiation Therapy n=21 Participants This is a single arm study; all participants will receive proton radiation therapy. Proton radiation therapy: 5 days per week (Mon-Fri) for 5-6 weeks
Acute Radiation Side Effects Platelet count decreased · Grade 1-mild	3 Participants
Acute Radiation Side Effects Skin and subcutaneous tissue disorders - other, specify · Grade 3-severe	0 Participants
Acute Radiation Side Effects Abdominal Pain · Not reported	18 Participants
Acute Radiation Side Effects Abdominal Pain · Grade 1-mild	2 Participants
Acute Radiation Side Effects Abdominal Pain · Grade 2-moderate	1 Participants
Acute Radiation Side Effects Abdominal Pain · Grade 3-severe	0 Participants
Acute Radiation Side Effects Anemia · Not reported	15 Participants
Acute Radiation Side Effects Anemia · Grade 1-mild	2 Participants
Acute Radiation Side Effects Anemia · Grade 2-moderate	4 Participants
Acute Radiation Side Effects Anemia · Grade 3-severe	0 Participants
Acute Radiation Side Effects Anorexia · Not reported	19 Participants
Acute Radiation Side Effects Anorexia · Grade 1-mild	2 Participants
Acute Radiation Side Effects Anorexia · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Anorexia · Grade 3-severe	0 Participants
Acute Radiation Side Effects Bladder spasm · Not reported	20 Participants
Acute Radiation Side Effects Bladder spasm · Grade 1-mild	0 Participants
Acute Radiation Side Effects Bladder spasm · Grade 2-moderate	1 Participants
Acute Radiation Side Effects Bladder spasm · Grade 3-severe	0 Participants
Acute Radiation Side Effects Bloating · Not reported	20 Participants
Acute Radiation Side Effects Bloating · Grade 1-mild	1 Participants
Acute Radiation Side Effects Bloating · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Bloating · Grade 3-severe	0 Participants
Acute Radiation Side Effects Constipation · Not reported	20 Participants
Acute Radiation Side Effects Constipation · Grade 1-mild	1 Participants
Acute Radiation Side Effects Constipation · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Constipation · Grade 3-severe	0 Participants
Acute Radiation Side Effects Cystitis noninfective · Not reported	20 Participants
Acute Radiation Side Effects Cystitis noninfective · Grade 1-mild	1 Participants
Acute Radiation Side Effects Cystitis noninfective · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Cystitis noninfective · Grade 3-severe	0 Participants
Acute Radiation Side Effects Dermatitis radiation · Not reported	12 Participants
Acute Radiation Side Effects Dermatitis radiation · Grade 1-mild	7 Participants
Acute Radiation Side Effects Dermatitis radiation · Grade 2-moderate	2 Participants
Acute Radiation Side Effects Dermatitis radiation · Grade 3-severe	0 Participants
Acute Radiation Side Effects Diarrhea · Not reported	6 Participants
Acute Radiation Side Effects Diarrhea · Grade 1-mild	10 Participants
Acute Radiation Side Effects Diarrhea · Grade 2-moderate	3 Participants
Acute Radiation Side Effects Diarrhea · Grade 3-severe	2 Participants
Acute Radiation Side Effects Fatigue · Not reported	3 Participants
Acute Radiation Side Effects Fatigue · Grade 1-mild	12 Participants
Acute Radiation Side Effects Fatigue · Grade 2-moderate	6 Participants
Acute Radiation Side Effects Fatigue · Grade 3-severe	0 Participants
Acute Radiation Side Effects Flatulence · Not reported	20 Participants
Acute Radiation Side Effects Flatulence · Grade 1-mild	1 Participants
Acute Radiation Side Effects Flatulence · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Flatulence · Grade 3-severe	0 Participants
Acute Radiation Side Effects Gastrointestinal disorders - Other, specify · Not reported	18 Participants
Acute Radiation Side Effects Gastrointestinal disorders - Other, specify · Grade 1-mild	2 Participants
Acute Radiation Side Effects Gastrointestinal disorders - Other, specify · Grade 2-moderate	1 Participants
Acute Radiation Side Effects Gastrointestinal disorders - Other, specify · Grade 3-severe	0 Participants
Acute Radiation Side Effects Hematuria · Not reported	20 Participants
Acute Radiation Side Effects Hematuria · Grade 1-mild	1 Participants
Acute Radiation Side Effects Hematuria · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Hematuria · Grade 3-severe	0 Participants
Acute Radiation Side Effects Hypokalemia · Not reported	20 Participants
Acute Radiation Side Effects Hypokalemia · Grade 1-mild	1 Participants
Acute Radiation Side Effects Hypokalemia · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Hypokalemia · Grade 3-severe	0 Participants
Acute Radiation Side Effects Infections and infestations - Other, specify · Not reported	20 Participants
Acute Radiation Side Effects Infections and infestations - Other, specify · Grade 1-mild	0 Participants
Acute Radiation Side Effects Infections and infestations - Other, specify · Grade 2-moderate	1 Participants
Acute Radiation Side Effects Infections and infestations - Other, specify · Grade 3-severe	0 Participants
Acute Radiation Side Effects Lymphocyte count decreased · Not reported	12 Participants
Acute Radiation Side Effects Lymphocyte count decreased · Grade 1-mild	1 Participants
Acute Radiation Side Effects Lymphocyte count decreased · Grade 2-moderate	4 Participants
Acute Radiation Side Effects Lymphocyte count decreased · Grade 3-severe	4 Participants
Acute Radiation Side Effects Nausea · Not reported	8 Participants
Acute Radiation Side Effects Nausea · Grade 1-mild	11 Participants
Acute Radiation Side Effects Nausea · Grade 2-moderate	2 Participants
Acute Radiation Side Effects Nausea · Grade 3-severe	0 Participants
Acute Radiation Side Effects Neutrophil count decreased · Not reported	20 Participants
Acute Radiation Side Effects Neutrophil count decreased · Grade 1-mild	0 Participants
Acute Radiation Side Effects Neutrophil count decreased · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Neutrophil count decreased · Grade 3-severe	1 Participants
Acute Radiation Side Effects Pain · Not reported	20 Participants
Acute Radiation Side Effects Pain · Grade 1-mild	1 Participants
Acute Radiation Side Effects Pain · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Pain · Grade 3-severe	0 Participants
Acute Radiation Side Effects Pelvic pain · Not reported	20 Participants
Acute Radiation Side Effects Pelvic pain · Grade 1-mild	1 Participants
Acute Radiation Side Effects Pelvic pain · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Pelvic pain · Grade 3-severe	0 Participants
Acute Radiation Side Effects Platelet count decreased · Not reported	15 Participants
Acute Radiation Side Effects Platelet count decreased · Grade 2-moderate	3 Participants
Acute Radiation Side Effects Platelet count decreased · Grade 3-severe	0 Participants
Acute Radiation Side Effects Proctitis · Not reported	18 Participants
Acute Radiation Side Effects Proctitis · Grade 1-mild	1 Participants
Acute Radiation Side Effects Proctitis · Grade 2-moderate	1 Participants
Acute Radiation Side Effects Proctitis · Grade 3-severe	1 Participants
Acute Radiation Side Effects Proteinuria · Not reported	20 Participants
Acute Radiation Side Effects Proteinuria · Grade 1-mild	1 Participants
Acute Radiation Side Effects Proteinuria · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Proteinuria · Grade 3-severe	0 Participants
Acute Radiation Side Effects Pruritis · Not reported	20 Participants
Acute Radiation Side Effects Pruritis · Grade 1-mild	1 Participants
Acute Radiation Side Effects Pruritis · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Pruritis · Grade 3-severe	0 Participants
Acute Radiation Side Effects Rectal hemorrhage · Not reported	19 Participants
Acute Radiation Side Effects Rectal hemorrhage · Grade 1-mild	2 Participants
Acute Radiation Side Effects Rectal hemorrhage · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Rectal hemorrhage · Grade 3-severe	0 Participants
Acute Radiation Side Effects Rectal pain · Not reported	17 Participants
Acute Radiation Side Effects Rectal pain · Grade 1-mild	4 Participants
Acute Radiation Side Effects Rectal pain · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Rectal pain · Grade 3-severe	0 Participants
Acute Radiation Side Effects Renal and urinary disorders - other, specify · Not reported	18 Participants
Acute Radiation Side Effects Renal and urinary disorders - other, specify · Grade 1-mild	3 Participants
Acute Radiation Side Effects Renal and urinary disorders - other, specify · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Renal and urinary disorders - other, specify · Grade 3-severe	0 Participants
Acute Radiation Side Effects Reproductive system and breast disorders - other, specify · Not reported	19 Participants
Acute Radiation Side Effects Reproductive system and breast disorders - other, specify · Grade 1-mild	1 Participants
Acute Radiation Side Effects Reproductive system and breast disorders - other, specify · Grade 2-moderate	1 Participants
Acute Radiation Side Effects Reproductive system and breast disorders - other, specify · Grade 3-severe	0 Participants
Acute Radiation Side Effects Skin and subcutaneous tissue disorders - other, specify · Not reported	18 Participants
Acute Radiation Side Effects Skin and subcutaneous tissue disorders - other, specify · Grade 1-mild	2 Participants
Acute Radiation Side Effects Skin and subcutaneous tissue disorders - other, specify · Grade 2-moderate	1 Participants
Acute Radiation Side Effects Stomach pain · Not reported	20 Participants
Acute Radiation Side Effects Stomach pain · Grade 1-mild	1 Participants
Acute Radiation Side Effects Stomach pain · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Stomach pain · Grade 3-severe	0 Participants
Acute Radiation Side Effects Superficial thrombophlebitis · Not reported	20 Participants
Acute Radiation Side Effects Superficial thrombophlebitis · Grade 1-mild	0 Participants
Acute Radiation Side Effects Superficial thrombophlebitis · Grade 2-moderate	1 Participants
Acute Radiation Side Effects Superficial thrombophlebitis · Grade 3-severe	0 Participants
Acute Radiation Side Effects Urinary frequency · Not reported	17 Participants
Acute Radiation Side Effects Urinary frequency · Grade 1-mild	4 Participants
Acute Radiation Side Effects Urinary frequency · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Urinary frequency · Grade 3-severe	0 Participants
Acute Radiation Side Effects urinary tract infection · Not reported	20 Participants
Acute Radiation Side Effects urinary tract infection · Grade 1-mild	0 Participants
Acute Radiation Side Effects urinary tract infection · Grade 2-moderate	1 Participants
Acute Radiation Side Effects urinary tract infection · Grade 3-severe	0 Participants
Acute Radiation Side Effects Urinary tract pain · Not reported	16 Participants
Acute Radiation Side Effects Urinary tract pain · Grade 1-mild	4 Participants
Acute Radiation Side Effects Urinary tract pain · Grade 2-moderate	1 Participants
Acute Radiation Side Effects Urinary tract pain · Grade 3-severe	0 Participants
Acute Radiation Side Effects Urinary urgency · Not reported	17 Participants
Acute Radiation Side Effects Urinary urgency · Grade 1-mild	4 Participants
Acute Radiation Side Effects Urinary urgency · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Urinary urgency · Grade 3-severe	0 Participants
Acute Radiation Side Effects Vaginal discharge · Not reported	19 Participants
Acute Radiation Side Effects Vaginal discharge · Grade 1-mild	2 Participants
Acute Radiation Side Effects Vaginal discharge · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Vaginal discharge · Grade 3-severe	0 Participants
Acute Radiation Side Effects Vaginal dryness · Not reported	19 Participants
Acute Radiation Side Effects Vaginal dryness · Grade 1-mild	2 Participants
Acute Radiation Side Effects Vaginal dryness · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Vaginal dryness · Grade 3-severe	0 Participants
Acute Radiation Side Effects Vaginal inflammation · Not reported	19 Participants
Acute Radiation Side Effects Vaginal inflammation · Grade 1-mild	0 Participants
Acute Radiation Side Effects Vaginal inflammation · Grade 2-moderate	2 Participants
Acute Radiation Side Effects Vaginal inflammation · Grade 3-severe	0 Participants
Acute Radiation Side Effects Vaginal pain · Not reported	15 Participants
Acute Radiation Side Effects Vaginal pain · Grade 1-mild	6 Participants
Acute Radiation Side Effects Vaginal pain · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Vaginal pain · Grade 3-severe	0 Participants
Acute Radiation Side Effects Vomiting · Not reported	20 Participants
Acute Radiation Side Effects Vomiting · Grade 1-mild	1 Participants
Acute Radiation Side Effects Vomiting · Grade 2-moderate	0 Participants
Acute Radiation Side Effects Vomiting · Grade 3-severe	0 Participants
Acute Radiation Side Effects While blood cell decreased · Not reported	14 Participants
Acute Radiation Side Effects While blood cell decreased · Grade 1-mild	5 Participants
Acute Radiation Side Effects While blood cell decreased · Grade 2-moderate	1 Participants
Acute Radiation Side Effects While blood cell decreased · Grade 3-severe	1 Participants

PRIMARY outcome

Timeframe: 5 years

Population: 22 subjects enrolled, and 1 subject withdrew consent prior to treatment. The remaining 21 subjects were analyzed.

Delayed complications from radiation were prospectively assessed. Below are the treatment-related late toxicities (adverse events possibly, probably, or definitely related to protocol treatment that started 6 months or later after treatment completion) that occurred on study, along with the number of participants who experienced each event at a given severity (Grade 1/mild, Grade 2/moderate, Grade 3/severe) according to the CTCAE v 4.02 (Common terminology criteria for adverse events).

Outcome measures

Measure	Proton Radiation Therapy n=21 Participants This is a single arm study; all participants will receive proton radiation therapy. Proton radiation therapy: 5 days per week (Mon-Fri) for 5-6 weeks
Delayed Radiation Complications Lymphocyte count decreased · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Psychiatric disorders - other, specify · Not reported	20 Participants
Delayed Radiation Complications Vaginal discharge · Not reported	20 Participants
Delayed Radiation Complications Vaginal dryness · Not reported	17 Participants
Delayed Radiation Complications Vaginal dryness · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Small intestinal obstruction · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Small intestinal obstruction · Grade 3 (Severe	1 Participants
Delayed Radiation Complications Telangiectasia · Not reported	17 Participants
Delayed Radiation Complications Telangiectasia · Grade 1 (mild)	4 Participants
Delayed Radiation Complications Telangiectasia · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Telangiectasia · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Urinary frequency · Not reported	17 Participants
Delayed Radiation Complications Urinary frequency · Grade 1 (mild)	4 Participants
Delayed Radiation Complications Urinary frequency · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Urinary frequency · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Urinary incontinence · Not reported	19 Participants
Delayed Radiation Complications Urinary incontinence · Grade 1 (mild)	2 Participants
Delayed Radiation Complications Urinary incontinence · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Urinary incontinence · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Urinary retention · Not reported	20 Participants
Delayed Radiation Complications Abdominal distension · Not reported	20 Participants
Delayed Radiation Complications Abdominal distension · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Abdominal distension · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Abdominal distension · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Abdominal pain · Not reported	18 Participants
Delayed Radiation Complications Abdominal pain · Grade 1 (mild)	2 Participants
Delayed Radiation Complications Abdominal pain · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Abdominal pain · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Anal pain · Not reported	20 Participants
Delayed Radiation Complications Anal pain · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Anal pain · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Anal pain · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Anemia · Not reported	20 Participants
Delayed Radiation Complications Anemia · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Anemia · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Anemia · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Constipation · Not reported	20 Participants
Delayed Radiation Complications Constipation · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Constipation · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Constipation · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Cystitis noninfective · Not reported	20 Participants
Delayed Radiation Complications Cystitis noninfective · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Cystitis noninfective · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Cystitis noninfective · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Dermatitis radiation · Not reported	20 Participants
Delayed Radiation Complications Dermatitis radiation · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Dermatitis radiation · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Dermatitis radiation · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Diarrhea · Not reported	16 Participants
Delayed Radiation Complications Diarrhea · Grade 1 (mild)	4 Participants
Delayed Radiation Complications Diarrhea · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Diarrhea · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Dry skin · Not reported	20 Participants
Delayed Radiation Complications Dry skin · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Dry skin · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Dry skin · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Duodenal ulcer · Not reported	20 Participants
Delayed Radiation Complications Duodenal ulcer · Grade 1 (mild)	0 Participants
Delayed Radiation Complications Duodenal ulcer · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Duodenal ulcer · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Dyspareunia · Not reported	19 Participants
Delayed Radiation Complications Dyspareunia · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Dyspareunia · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Dyspareunia · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Edema limbs · Not reported	19 Participants
Delayed Radiation Complications Edema limbs · Grade 1 (mild)	2 Participants
Delayed Radiation Complications Edema limbs · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Edema limbs · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Fatigue · Not reported	17 Participants
Delayed Radiation Complications Fatigue · Grade 1 (mild)	3 Participants
Delayed Radiation Complications Fatigue · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Fatigue · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Fecal incontinence · Not reported	15 Participants
Delayed Radiation Complications Fecal incontinence · Grade 1 (mild)	6 Participants
Delayed Radiation Complications Fecal incontinence · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Fecal incontinence · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Flatulence · Not reported	20 Participants
Delayed Radiation Complications Flatulence · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Flatulence · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Flatulence · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Gastritis · Not reported	20 Participants
Delayed Radiation Complications Gastritis · Grade 1 (mild)	0 Participants
Delayed Radiation Complications Gastritis · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Gastritis · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Gastrointestinal disorders - other, specify · Not reported	17 Participants
Delayed Radiation Complications Gastrointestinal disorders - other, specify · Grade 1 (mild)	4 Participants
Delayed Radiation Complications Gastrointestinal disorders - other, specify · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Gastrointestinal disorders - other, specify · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Hematuria · Not reported	19 Participants
Delayed Radiation Complications Hematuria · Grade 1 (mild)	2 Participants
Delayed Radiation Complications Hematuria · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Hematuria · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Hemorrhoids · Not reported	20 Participants
Delayed Radiation Complications Hemorrhoids · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Hemorrhoids · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Hemorrhoids · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Libido decreased · Not reported	20 Participants
Delayed Radiation Complications Libido decreased · Grade 1 (mild)	0 Participants
Delayed Radiation Complications Libido decreased · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Libido decreased · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Lymphedema · Not reported	15 Participants
Delayed Radiation Complications Lymphedema · Grade 1 (mild)	5 Participants
Delayed Radiation Complications Lymphedema · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Lymphedema · Grade 3 (Severe	1 Participants
Delayed Radiation Complications Lymphocyte count decreased · Not reported	16 Participants
Delayed Radiation Complications Lymphocyte count decreased · Grade 1 (mild)	4 Participants
Delayed Radiation Complications Lymphocyte count decreased · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Nausea · Not reported	19 Participants
Delayed Radiation Complications Nausea · Grade 1 (mild)	2 Participants
Delayed Radiation Complications Nausea · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Nausea · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Paresthesia · Not reported	20 Participants
Delayed Radiation Complications Paresthesia · Grade 1 (mild)	0 Participants
Delayed Radiation Complications Paresthesia · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Paresthesia · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Pelvic pain · Not reported	18 Participants
Delayed Radiation Complications Pelvic pain · Grade 1 (mild)	3 Participants
Delayed Radiation Complications Pelvic pain · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Pelvic pain · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Proctitis · Not reported	19 Participants
Delayed Radiation Complications Proctitis · Grade 1 (mild)	2 Participants
Delayed Radiation Complications Proctitis · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Proctitis · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Psychiatric disorders - other, specify · Grade 1 (mild)	0 Participants
Delayed Radiation Complications Psychiatric disorders - other, specify · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Psychiatric disorders - other, specify · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Rectal hemorrhage · Not reported	20 Participants
Delayed Radiation Complications Rectal hemorrhage · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Rectal hemorrhage · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Rectal hemorrhage · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Renal and urinary disorders - other, specify · Not reported	18 Participants
Delayed Radiation Complications Renal and urinary disorders - other, specify · Grade 1 (mild)	2 Participants
Delayed Radiation Complications Renal and urinary disorders - other, specify · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Renal and urinary disorders - other, specify · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Reproductive system and breast disorders - other, specify · Not reported	17 Participants
Delayed Radiation Complications Reproductive system and breast disorders - other, specify · Grade 1 (mild)	4 Participants
Delayed Radiation Complications Reproductive system and breast disorders - other, specify · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Reproductive system and breast disorders - other, specify · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Small intestinal obstruction · Not reported	20 Participants
Delayed Radiation Complications Small intestinal obstruction · Grade 1 (mild)	0 Participants
Delayed Radiation Complications Urinary retention · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Urinary retention · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Urinary retention · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Urinary tract pain · Not reported	20 Participants
Delayed Radiation Complications Urinary tract pain · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Urinary tract pain · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Urinary tract pain · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Vaginal discharge · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Vaginal discharge · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Vaginal discharge · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Vaginal dryness · Grade 1 (mild)	3 Participants
Delayed Radiation Complications Vaginal dryness · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Vaginal hemorrhage · Not reported	18 Participants
Delayed Radiation Complications Vaginal hemorrhage · Grade 1 (mild)	3 Participants
Delayed Radiation Complications Vaginal hemorrhage · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Vaginal hemorrhage · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Vaginal inflammation · Not reported	20 Participants
Delayed Radiation Complications Vaginal inflammation · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Vaginal inflammation · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Vaginal inflammation · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Vaginal obstruction · Not reported	20 Participants
Delayed Radiation Complications Vaginal obstruction · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Vaginal obstruction · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Vaginal obstruction · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Vaginal pain · Not reported	18 Participants
Delayed Radiation Complications Vaginal pain · Grade 1 (mild)	2 Participants
Delayed Radiation Complications Vaginal pain · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Vaginal pain · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Vaginal stricture · Not reported	19 Participants
Delayed Radiation Complications Vaginal stricture · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Vaginal stricture · Grade 2 (moderate)	1 Participants
Delayed Radiation Complications Vaginal stricture · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Vomiting · Not reported	20 Participants
Delayed Radiation Complications Vomiting · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Vomiting · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Vomiting · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Vulval infection · Not reported	20 Participants
Delayed Radiation Complications Vulval infection · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Vulval infection · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Vulval infection · Grade 3 (Severe	0 Participants
Delayed Radiation Complications Weight gain · Not reported	20 Participants
Delayed Radiation Complications Weight gain · Grade 1 (mild)	1 Participants
Delayed Radiation Complications Weight gain · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications Weight gain · Grade 3 (Severe	0 Participants
Delayed Radiation Complications White blood cell decreased · Not reported	20 Participants
Delayed Radiation Complications White blood cell decreased · Grade 1 (mild)	1 Participants
Delayed Radiation Complications White blood cell decreased · Grade 2 (moderate)	0 Participants
Delayed Radiation Complications White blood cell decreased · Grade 3 (Severe	0 Participants

SECONDARY outcome

Timeframe: Baseline, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years

Population: 22 patients were enrolled, 1 of whom withdrew consent prior to study treatment. The remaining 21 subjects were analyzed.

The total FACT-EN/Cx scale (Functional Assessment of Cancer Therapy - Endometrial/Cervical) score was assessed at baseline and timepoints of 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years to evaluate quality of life (QOL) before and after adjuvant scanning proton beam therapy.

Unit = Scores on a scale. Subset scores are summed together to get a total score.

Functional Assessment of Cancer Therapy - Endometrial - score range 0 - 172, with higher scores indicating a better outcome Functional Assessment of Cancer Therapy - Cervical - score range 0 - 168, with higher scores indicating a better outcome

Outcome measures

Measure	Proton Radiation Therapy n=21 Participants This is a single arm study; all participants will receive proton radiation therapy. Proton radiation therapy: 5 days per week (Mon-Fri) for 5-6 weeks
Quality of Life (QOL) Baseline	128.67 total score on FACT-EN/Cx scale Standard Deviation 25.88
Quality of Life (QOL) 6 months	133.47 total score on FACT-EN/Cx scale Standard Deviation 29.55
Quality of Life (QOL) 1 year	131.53 total score on FACT-EN/Cx scale Standard Deviation 27.49
Quality of Life (QOL) 2 years	133.65 total score on FACT-EN/Cx scale Standard Deviation 25.71
Quality of Life (QOL) 3 years	139.13 total score on FACT-EN/Cx scale Standard Deviation 24.62
Quality of Life (QOL) 4 years	142.88 total score on FACT-EN/Cx scale Standard Deviation 21.93
Quality of Life (QOL) 5 years	149.39 total score on FACT-EN/Cx scale Standard Deviation 14.30

SECONDARY outcome

Timeframe: 12 months, 24 months, 36 months, 48 months, and 60 months

Population: 22 patients were enrolled, 1 of whom withdrew prior to study treatment. The remaining 21 patients were included in this analysis.

PFS is defined as the duration of time from start of treatment to time of objective disease progression at any site as detected by symptomatic recurrence or routine surveillance follow-up physical examination/imaging, or death from any cause.

Outcome measures

Measure	Proton Radiation Therapy n=21 Participants This is a single arm study; all participants will receive proton radiation therapy. Proton radiation therapy: 5 days per week (Mon-Fri) for 5-6 weeks
Progression-free Survival (PFS) 12 months post treatment completion	85.7 percentage of participants Interval 62.0 to 95.2
Progression-free Survival (PFS) 24 months post treatment completion	80.7 percentage of participants Interval 56.3 to 92.3
Progression-free Survival (PFS) 36 months post treatment completion	75.6 percentage of participants Interval 50.9 to 89.1
Progression-free Survival (PFS) 48 months post treatment completion	75.6 percentage of participants Interval 50.9 to 89.1
Progression-free Survival (PFS) 60 months post treatment completion	75.6 percentage of participants Interval 50.9 to 89.1

Adverse Events

Proton Radiation Therapy

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Proton Radiation Therapy n=21 participants at risk This is a single arm study; all participants will receive proton radiation therapy. Proton radiation therapy: 5 days per week (Mon-Fri) for 5-6 weeks
Metabolism and nutrition disorders Dehydration	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Dental caries	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Depression	23.8% 5/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Injury, poisoning and procedural complications Dermatitis radiation	47.6% 10/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Diarrhea	76.2% 16/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Dizziness	28.6% 6/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Dry mouth	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Dry skin	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Abdominal distension	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Abdominal pain	57.1% 12/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Acute kidney injury	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Agitation	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Investigations Alkaline phosphatase increased	28.6% 6/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Immune system disorders Allergic reaction	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Alopecia	23.8% 5/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Amnesia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Anal hemorrhage	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Anal pain	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Blood and lymphatic system disorders Anemia	61.9% 13/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Anorexia	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Anxiety	42.9% 9/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Apnea	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Arthralgia	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Arthritis	23.8% 5/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Ascites	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Atelectasis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Atrial fibrillation	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Atrial flutter	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Immune system disorders Autoimmune disorder	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Back pain	42.9% 9/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Bladder spasm	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Bloating	23.8% 5/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify: Iron deficiency	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify: Mucosal hyperemia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Investigations Blood corticotrophin decreased	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Bone pain	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Breast pain	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Injury, poisoning and procedural complications Bruising	23.8% 5/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Buttock pain	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Cardiac disorders - Other, specify: Carotid bruit	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Cardiac disorders - Other, specify: Abdominal aortic pulsation	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Cardiac disorders - Other, specify: Dilated cardiomyopathy	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Cardiac disorders - Other, specify: systolic murmur	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Cardiac disorders - Other, specify	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Cataract	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Chest pain - cardiac	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Chills	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Hepatobiliary disorders Cholecystitis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Investigations Cholesterol high	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Colitis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Confusion	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Constipation	90.5% 19/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Cystitis noninfective	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Duodenal hemorrhage	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Duodenal ulcer	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Dysgeusia	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Dyspareunia	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Dyspepsia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Dyspnea	47.6% 10/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Ear and labyrinth disorders Ear pain	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Edema face	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Edema limbs	57.1% 12/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Endocrine disorders Endocrine disorders - Other, specify: bilateral small hypoechoic nodules; benign appearance	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Endocrine disorders Endocrine disorders - Other, specify: Multinodular goiter	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Enterocolitis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Erythema multiforme	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Eye disorders - Other, specify: exopthalmos	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Eye disorders - Other, specify: Left upper lid pain - swollen, crusty discharge	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Eye disorders - Other, specify: hordeolum externum of left upper eyelid	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Eye disorders - Other, specify: pain and swelling in Right upper eyelid	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Eye disorders - Other, specify: pathologic myopia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Eye disorders - Other, specify: asthenopia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Eye disorders - Other, specify: meibomian gland dysfunction	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Eye pain	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Injury, poisoning and procedural complications Fall	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Fatigue	95.2% 20/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Fecal incontinence	52.4% 11/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Fever	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Flatulence	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Floaters	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Flu like symptoms	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Vascular disorders Flushing	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Injury, poisoning and procedural complications Fracture	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Gait disturbance	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastritis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastroesophageal reflux disease	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: history of crohn's disease	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: small bowel obstruction	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: abdominal spasms	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Rectal urgency	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Diverticulosis	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Rectal discharge	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Abdominal discomfort secondary to oral contrast agent	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Hiatal hernia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Melena	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Hematochezia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Rectocele	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Irritable bowel syndrome	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: Bowel urgency	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: increased frequency of bowel movements	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders General disorders and administration site conditions - Other, specify: Diaphoresis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders General disorders and administration site conditions - Other, specify: lesion on finger	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Glaucoma	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Gum infection	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Hallucinations	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Headache	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Ear and labyrinth disorders Hearing impaired	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Heart failure	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Hematuria	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Hemorrhoidal hemorrhage	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Hemorrhoids	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify: cholelithisasis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Hirsutism	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Hoarseness	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Vascular disorders Hot flashes	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Hyperglycemia	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Hyperhidrosis	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Hyperkalemia	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Vascular disorders Hypertension	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Endocrine disorders Hyperthyroidism	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Hypertriglyceridemia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Hypoalbuminemia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Hypocalcemia	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Hypokalemia	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Hypomagnesemia	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Hyponatremia	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Hypophosphatemia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Vascular disorders Hypotension	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Endocrine disorders Hypothyroidism	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Hypoxia	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Infections and infestations - Other, specify: herpes simplex virus	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Infections and infestations - Other, specify: tooth infection	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Infections and infestations - Other, specify: yeast infection	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify: rotator cuff tear	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify: port site pain	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Investigations INR increased	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Insomnia	28.6% 6/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Irritability	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Kidney infection	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Libido decreased	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Lip infection	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Localized edema	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Vascular disorders Lymphedema	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Investigations Lymphocyte count decreased	61.9% 13/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify: Insulin resistance	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify: lactic acidosis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify: vitamin D deficiency	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: hip pain	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: knee pain	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: plantar lesion	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: Soft bulging when standing up	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: degenerative disc disease	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: finger pain	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: subacromial spur w/ tendinopathy	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: hyperreflexia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: Sciatica	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: Fibromyalgia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: osteitis deformans	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: Musculoskeletal deformity	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Myalgia	28.6% 6/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Nail discoloration	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Nail infection	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Nail loss	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Nasal congestion	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Nausea	85.7% 18/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Neck pain	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify: Vascular polyp	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify: Baker's cyst	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify: Cyst	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify: Ganglion cyst	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Nervous system disorders - Other, specify: hyperreflexia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Nervous system disorders - Other, specify	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Nervous system disorders - Other, specify: Carpal tunnel syndrome	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Neuralgia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Investigations Neutrophil count decreased	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Non-cardiac chest pain	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Metabolism and nutrition disorders Obesity	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Oral pain	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
General disorders Pain	47.6% 10/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Musculoskeletal and connective tissue disorders Pain in extremity	28.6% 6/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Palpitations	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Paresthesia	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Pelvic pain	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Periorbital edema	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Peripheral motor neuropathy	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Peripheral sensory neuropathy	57.1% 12/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Pharyngitis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Photosensitivity	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Investigations Platelet count decreased	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Postnasal drip	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Premature menopause	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Proctitis	23.8% 5/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Productive cough	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Proteinuria	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Pruritus	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Psychiatric disorders - Other, specify: PTSD	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Psychiatric disorders - Other, specify: Recent cognitive struggles, sleep disruption and sadness.	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Psychiatric disorders - Other, specify: ADHD	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Rash acneiform	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Rash maculo-papular	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Rectal hemorrhage	23.8% 5/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Rectal mucositis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Rectal pain	28.6% 6/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Renal and urinary disorders - Other, specify: Dysuria	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Renal and urinary disorders - Other, specify: Bladder pressure and urinary frequency	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Renal and urinary disorders - Other, specify: Mons swelling	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Renal and urinary disorders - Other, specify: cytocele	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Renal and urinary disorders - Other, specify: Urinary leakage	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Renal and urinary disorders - Other, specify: Suprapubic pressure and discomfort with urination	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: changes to vaginal mucosa	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Synechiae in vagina	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: radiation changes in vagina	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Vaginal bleeding	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Radiation stigmata	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Yeast infection	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Vaginal discharge discoloration	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Vaginitis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Vaginal bleeding during intercourse	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Post-coital bleeding	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Perineal erythema	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Vaginal atrophy	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Vaginal mucosa atrophy	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Mons pubis swelling, pressure, discomfort	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Mild hyperemia of vagina	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Radiation changes/erythema at the cuff	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Vaginal burning	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Radiation fibrosis of vaginal rugae	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Enlarged veins R labial vulvar region	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: Sphincter tone decreased	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify: vulva lesions	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify: Tachypnea	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Eye disorders Retinal tear	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Sepsis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Sinus bradycardia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Sinus pain	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Cardiac disorders Sinus tachycardia	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: Ingrown toenail	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify: rash	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin induration	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Skin infection	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: Rash on inner surface of elbows	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other: Erythematous macular rash, venous stasis dermatitis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: Seborrheic keratosis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: Slight pinkness on chest	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: Skin tag swollen and painful left axilla	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: Yeast dermatitis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: perineal itching	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: itchy rash on arms	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: Perineal irritation	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: Onychocryptosis	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: Erythema	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: lichen planus	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Skin/subcutaneous tissue disorders; Other, specify: Eczema	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Sleep apnea	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Small intestinal obstruction	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Sore throat	19.0% 4/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Spasticity	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Injury, poisoning and procedural complications Spinal fracture	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Stomach pain	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Psychiatric disorders Suicidal ideation	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Vascular disorders Superficial thrombophlebitis	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Surgical and medical procedures Surgical and medical procedures - Other, specify: Laparoscopic gastric bypass surgery	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Syncope	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Skin and subcutaneous tissue disorders Telangiectasia	28.6% 6/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Vascular disorders Thromboembolic event	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Ear and labyrinth disorders Tinnitus	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Tooth infection	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Nervous system disorders Tremor	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Upper respiratory infection	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Urinary frequency	61.9% 13/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Urinary incontinence	42.9% 9/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Urinary retention	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Urinary tract infection	28.6% 6/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Urinary tract pain	42.9% 9/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Renal and urinary disorders Urinary urgency	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Vaginal discharge	23.8% 5/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Vaginal dryness	28.6% 6/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Vaginal hemorrhage	38.1% 8/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Vaginal infection	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Vaginal inflammation	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Vaginal obstruction	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Vaginal pain	57.1% 12/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Reproductive system and breast disorders Vaginal stricture	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Injury, poisoning and procedural complications Vascular access complication	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Vascular disorders Vascular disorders - Other, specify: Peripheral artery disease	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Vascular disorders Vascular disorders - Other, specify: Varicose veins	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Vascular disorders Vascular disorders - Other, specify: Venous incompetence	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Ear and labyrinth disorders Vertigo	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Gastrointestinal disorders Vomiting	42.9% 9/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Vulval infection	14.3% 3/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Investigations Weight gain	23.8% 5/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Investigations Weight loss	33.3% 7/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Respiratory, thoracic and mediastinal disorders Wheezing	9.5% 2/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Investigations White blood cell decreased	38.1% 8/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.
Infections and infestations Wound infection	4.8% 1/21 • Adverse events will be collected and reported from initiation of study treatment until 60 months after the last dose of study medication/radiation treatment (5 years). This was assessed every 3 months years 1-2 post-treatment, every 4 months year 3, and every 6 months until 5 years from the end of the last dose of radiation.

Additional Information

Andrea Russo, MD

Massachusetts General Hospital

Phone: 617-726-7941

Email: alrusso@mgh.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place