Trial Outcomes & Findings for A Randomized Comparison of Radiation Therapy Techniques in the Management of Node Positive Breast Cancer (NCT NCT00581256)

Last Updated: 2017-10-31

Results Overview

To compare the extent of new myocardial perfusion defects following breast cancer radiotherapy using the best standard 3-D radiotherapy technique, partially wide tangent fields, versus the best optimized technique. Perfusion defects (PD) were assessed by comparing normalized perfusion distributions against our institution's normal polar map databases for the left anterior descending artery (LAD) using thresholds of 2.5-SD (standard deviation) and 1.5-SD below the normal mean. On the basis of interest variability, a PD increase greater than 5% or 10% was considered significant for 2.5- and 1.5-SD thresholds, respectively.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

54 participants

Primary outcome timeframe

1 Year

Results posted on

2017-10-31

Participant Flow

Participant milestones

Participant milestones
Measure	IMRT Best Delivery-optimized radiotherapy technique (IMRT) IMRT: All patients treated with the optimized plan will be treated to the entire target volume to 52.2 Gy in 1.74 Gy fractions, which is biologically equivalent to 50 Gy in 2 Gy fractions. This fractionation scheme will allow the boost of 10 Gy to be incorporated into the planning directive and to be delivered simultaneously with the treatment to the remaining target volume.	3DRT Best 3-dimensional standard PWTF technique 3D: All patients treated using the best standard technique will receive 50 Gy in 2 Gy fractions or 50.4 Gy in 1.8 Gy fractions to the entire target volume delivering one treatment per day, five fractions per week (excluding holidays). A boost of 10 Gy to the tumor bed of an intact breast will be delivered. Patients treated to the chest wall will receive a 10Gy scar boost if mastectomy margins are positive in a patient with Stage II disease or if the patient was originally diagnosed with T3 or T4 (Stage III) disease
Overall Study STARTED	28	26
Overall Study COMPLETED	28	26
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomized Comparison of Radiation Therapy Techniques in the Management of Node Positive Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IMRT n=28 Participants Best Delivery-optimized radiotherapy technique (IMRT) IMRT: All patients treated with the optimized plan will be treated to the entire target volume to 52.2 Gy in 1.74 Gy fractions, which is biologically equivalent to 50 Gy in 2 Gy fractions. This fractionation scheme will allow the boost of 10 Gy to be incorporated into the planning directive and to be delivered simultaneously with the treatment to the remaining target volume.	3DRT n=26 Participants Best 3-dimensional standard PWTF technique 3D: All patients treated using the best standard technique will receive 50 Gy in 2 Gy fractions or 50.4 Gy in 1.8 Gy fractions to the entire target volume delivering one treatment per day, five fractions per week (excluding holidays). A boost of 10 Gy to the tumor bed of an intact breast will be delivered. Patients treated to the chest wall will receive a 10Gy scar boost if mastectomy margins are positive in a patient with Stage II disease or if the patient was originally diagnosed with T3 or T4 (Stage III) disease	Total n=54 Participants Total of all reporting groups
Age, Continuous	47.8 years n=5 Participants	51.7 years n=7 Participants	50.6 years n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	25 Participants n=7 Participants	53 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 Year

Outcome measures

Outcome measures
Measure	IMRT n=28 Participants Best Delivery-optimized radiotherapy technique (IMRT) IMRT: All patients treated with the optimized plan will be treated to the entire target volume to 52.2 Gy in 1.74 Gy fractions, which is biologically equivalent to 50 Gy in 2 Gy fractions. This fractionation scheme will allow the boost of 10 Gy to be incorporated into the planning directive and to be delivered simultaneously with the treatment to the remaining target volume.	3DRT n=26 Participants Best 3-dimensional standard PWTF technique 3D: All patients treated using the best standard technique will receive 50 Gy in 2 Gy fractions or 50.4 Gy in 1.8 Gy fractions to the entire target volume delivering one treatment per day, five fractions per week (excluding holidays). A boost of 10 Gy to the tumor bed of an intact breast will be delivered. Patients treated to the chest wall will receive a 10Gy scar boost if mastectomy margins are positive in a patient with Stage II disease or if the patient was originally diagnosed with T3 or T4 (Stage III) disease
The Number of Participants With a Significant Increase in Perfusion Defects (PD) 2.5 SD and PD increase >5%	1 participants	2 participants
The Number of Participants With a Significant Increase in Perfusion Defects (PD) 1.5 SD and PD increase >10%	3 participants	5 participants

SECONDARY outcome

Timeframe: baseline to approx 1 year

To compare change in ejection fraction between treatment arms.

Outcome measures

Outcome measures
Measure	IMRT n=28 Participants Best Delivery-optimized radiotherapy technique (IMRT) IMRT: All patients treated with the optimized plan will be treated to the entire target volume to 52.2 Gy in 1.74 Gy fractions, which is biologically equivalent to 50 Gy in 2 Gy fractions. This fractionation scheme will allow the boost of 10 Gy to be incorporated into the planning directive and to be delivered simultaneously with the treatment to the remaining target volume.	3DRT n=26 Participants Best 3-dimensional standard PWTF technique 3D: All patients treated using the best standard technique will receive 50 Gy in 2 Gy fractions or 50.4 Gy in 1.8 Gy fractions to the entire target volume delivering one treatment per day, five fractions per week (excluding holidays). A boost of 10 Gy to the tumor bed of an intact breast will be delivered. Patients treated to the chest wall will receive a 10Gy scar boost if mastectomy margins are positive in a patient with Stage II disease or if the patient was originally diagnosed with T3 or T4 (Stage III) disease
Mean Percent Change in Ejection Fraction (LVEF)	3 percent change Interval -7.0 to 18.0	-2 percent change Interval -16.0 to 11.0

SECONDARY outcome

Timeframe: baseline to approx 1 year

Population: One patient randomized to the IMRT arm did not receive her post-RT lung SPECT scan therefore pre- and post-radiotherapy Lung SPECT scans were available for 53 patients.

To compare changes in lung perfusion defects by treatment arm. Perfusion defects (PD) were assessed by comparing normalized perfusion distributions against our institution's normal polar map databases for the left anterior descending artery (LAD).

Outcome measures

Outcome measures
Measure	IMRT n=27 Participants Best Delivery-optimized radiotherapy technique (IMRT) IMRT: All patients treated with the optimized plan will be treated to the entire target volume to 52.2 Gy in 1.74 Gy fractions, which is biologically equivalent to 50 Gy in 2 Gy fractions. This fractionation scheme will allow the boost of 10 Gy to be incorporated into the planning directive and to be delivered simultaneously with the treatment to the remaining target volume.	3DRT n=26 Participants Best 3-dimensional standard PWTF technique 3D: All patients treated using the best standard technique will receive 50 Gy in 2 Gy fractions or 50.4 Gy in 1.8 Gy fractions to the entire target volume delivering one treatment per day, five fractions per week (excluding holidays). A boost of 10 Gy to the tumor bed of an intact breast will be delivered. Patients treated to the chest wall will receive a 10Gy scar boost if mastectomy margins are positive in a patient with Stage II disease or if the patient was originally diagnosed with T3 or T4 (Stage III) disease
Number of Participants With New Lung Perfusion Defects	3 participants	5 participants

SECONDARY outcome

Timeframe: approx 1 year

To compare rates of pericarditis and pneumonitis by treatment arm. Pericarditis (inflammation of the pericardium): Grade1: Asymptomatic, ECG or physical exam; changes consistent with pericarditis Grade 2: Symptomatic pericarditis Grade 3: Pericarditis with physiologic consequences Grade 4: Life-threatening Pneumonitis (inflammation of the walls of the alveoli in the lungs) Grade 1: Asymptomatic, radiographic findings only Grade 2: Symptomatic, not interfering with ADL (activities of daily living) Grade 3: Symptomatic, interfering with ADL Grade 4: Life-threatening

Outcome measures

Outcome measures
Measure	IMRT n=28 Participants Best Delivery-optimized radiotherapy technique (IMRT) IMRT: All patients treated with the optimized plan will be treated to the entire target volume to 52.2 Gy in 1.74 Gy fractions, which is biologically equivalent to 50 Gy in 2 Gy fractions. This fractionation scheme will allow the boost of 10 Gy to be incorporated into the planning directive and to be delivered simultaneously with the treatment to the remaining target volume.	3DRT n=26 Participants Best 3-dimensional standard PWTF technique 3D: All patients treated using the best standard technique will receive 50 Gy in 2 Gy fractions or 50.4 Gy in 1.8 Gy fractions to the entire target volume delivering one treatment per day, five fractions per week (excluding holidays). A boost of 10 Gy to the tumor bed of an intact breast will be delivered. Patients treated to the chest wall will receive a 10Gy scar boost if mastectomy margins are positive in a patient with Stage II disease or if the patient was originally diagnosed with T3 or T4 (Stage III) disease
The Number of Participants That Experience Pericarditis and Pneumonitis Number of participants with pericarditis (Gr 1-4)	0 participants	0 participants
The Number of Participants That Experience Pericarditis and Pneumonitis Number of participants with pneumonitis (Gr 1-4)	0 participants	0 participants

Adverse Events

IMRT

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

3DRT

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IMRT n=28 participants at risk Best Delivery-optimized radiotherapy technique (IMRT) IMRT: All patients treated with the optimized plan will be treated to the entire target volume to 52.2 Gy in 1.74 Gy fractions, which is biologically equivalent to 50 Gy in 2 Gy fractions. This fractionation scheme will allow the boost of 10 Gy to be incorporated into the planning directive and to be delivered simultaneously with the treatment to the remaining target volume.	3DRT n=26 participants at risk Best 3-dimensional standard PWTF technique 3D: All patients treated using the best standard technique will receive 50 Gy in 2 Gy fractions or 50.4 Gy in 1.8 Gy fractions to the entire target volume delivering one treatment per day, five fractions per week (excluding holidays). A boost of 10 Gy to the tumor bed of an intact breast will be delivered. Patients treated to the chest wall will receive a 10Gy scar boost if mastectomy margins are positive in a patient with Stage II disease or if the patient was originally diagnosed with T3 or T4 (Stage III) disease
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils	3.6% 1/28	0.00% 0/26

Other adverse events

Other adverse events
Measure	IMRT n=28 participants at risk Best Delivery-optimized radiotherapy technique (IMRT) IMRT: All patients treated with the optimized plan will be treated to the entire target volume to 52.2 Gy in 1.74 Gy fractions, which is biologically equivalent to 50 Gy in 2 Gy fractions. This fractionation scheme will allow the boost of 10 Gy to be incorporated into the planning directive and to be delivered simultaneously with the treatment to the remaining target volume.	3DRT n=26 participants at risk Best 3-dimensional standard PWTF technique 3D: All patients treated using the best standard technique will receive 50 Gy in 2 Gy fractions or 50.4 Gy in 1.8 Gy fractions to the entire target volume delivering one treatment per day, five fractions per week (excluding holidays). A boost of 10 Gy to the tumor bed of an intact breast will be delivered. Patients treated to the chest wall will receive a 10Gy scar boost if mastectomy margins are positive in a patient with Stage II disease or if the patient was originally diagnosed with T3 or T4 (Stage III) disease
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	0.00% 0/28	3.8% 1/26
Investigations AST, SGOT(serum glutamic oxaloacetic transaminase)	0.00% 0/28	7.7% 2/26
Metabolism and nutrition disorders Anorexia	0.00% 0/28	3.8% 1/26
Reproductive system and breast disorders Breast nipple/areolar deformity	14.3% 4/28	19.2% 5/26
Reproductive system and breast disorders Breast volume/hypoplasia	32.1% 9/28	26.9% 7/26
Skin and subcutaneous tissue disorders Burn	3.6% 1/28	15.4% 4/26
Cardiac disorders Cardiac General - Other	0.00% 0/28	3.8% 1/26
Skin and subcutaneous tissue disorders Dermatology/Skin - Other	7.1% 2/28	3.8% 1/26
Gastrointestinal disorders Diarrhea	3.6% 1/28	3.8% 1/26
Skin and subcutaneous tissue disorders Dry skin	17.9% 5/28	11.5% 3/26
Vascular disorders Edema: limb	35.7% 10/28	42.3% 11/26
Vascular disorders Edema: trunk/genital	3.6% 1/28	7.7% 2/26
Musculoskeletal and connective tissue disorders Extremity-lower (gait/walking)	0.00% 0/28	3.8% 1/26
General disorders Fatigue (asthenia, lethargy, malaise)	32.1% 9/28	46.2% 12/26
Musculoskeletal and connective tissue disorders Fibrosis-deep connective tissue	0.00% 0/28	3.8% 1/26
Gastrointestinal disorders Gastrointestinal - Other	0.00% 0/28	3.8% 1/26
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	0.00% 0/28	3.8% 1/26
Skin and subcutaneous tissue disorders Hair loss/alopecia (scalp or body)	0.00% 0/28	3.8% 1/26
General disorders Hot flashes/flushes	3.6% 1/28	7.7% 2/26
Skin and subcutaneous tissue disorders Hyperpigmentation	78.6% 22/28	65.4% 17/26
Skin and subcutaneous tissue disorders Induration/fibrosis (skin and subcutaneous tissue)	39.3% 11/28	30.8% 8/26
Infections and infestations Infection with Grade 3 or 4 neutrophils	0.00% 0/28	3.8% 1/26
Reproductive system and breast disorders Irregular menses (change from baseline)	0.00% 0/28	3.8% 1/26
Musculoskeletal and connective tissue disorders Joint-function	0.00% 0/28	3.8% 1/26
Cardiac disorders Left ventricular diastolic dysfunction	0.00% 0/28	3.8% 1/26
Blood and lymphatic system disorders Leukocytes (total WBC)	0.00% 0/28	3.8% 1/26
Blood and lymphatic system disorders Lymphatics - Other	0.00% 0/28	3.8% 1/26
Blood and lymphatic system disorders Lymphedema-related fibrosis	7.1% 2/28	15.4% 4/26
Blood and lymphatic system disorders Lymphopenia	7.1% 2/28	3.8% 1/26
Psychiatric disorders Mood alteration	7.1% 2/28	7.7% 2/26
Musculoskeletal and connective tissue disorders Muscle weakness, generalized	7.1% 2/28	7.7% 2/26
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue - Other	3.6% 1/28	3.8% 1/26
Gastrointestinal disorders Nausea	3.6% 1/28	3.8% 1/26
Nervous system disorders Neuropathy: motor	3.6% 1/28	3.8% 1/26
General disorders Pain	25.0% 7/28	26.9% 7/26
General disorders Pain - Other	3.6% 1/28	3.8% 1/26
Skin and subcutaneous tissue disorders Pruritus/itching	3.6% 1/28	15.4% 4/26
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other	7.1% 2/28	7.7% 2/26
Skin and subcutaneous tissue disorders Rash/desquamation	10.7% 3/28	7.7% 2/26
Skin and subcutaneous tissue disorders Rash: dermatitis associated with radiation	39.3% 11/28	61.5% 16/26
Injury, poisoning and procedural complications Seroma	3.6% 1/28	3.8% 1/26
Reproductive system and breast disorders Sexual/Reproductive Function - Other	3.6% 1/28	3.8% 1/26
Investigations Sodium, serum-low (hyponatremia)	3.6% 1/28	3.8% 1/26
Vascular disorders Telangiectasia	32.1% 9/28	15.4% 4/26
Nervous system disorders Tremor	3.6% 1/28	3.8% 1/26
Reproductive system and breast disorders Vaginal dryness	3.6% 1/28	3.8% 1/26
Musculoskeletal and connective tissue disorders Arthritis (non-septic)	7.1% 2/28	0.00% 0/26
Skin and subcutaneous tissue disorders Atrophy, skin	3.6% 1/28	0.00% 0/26
Gastrointestinal disorders Constipation	3.6% 1/28	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Cough	3.6% 1/28	0.00% 0/26
Investigations Creatinine	3.6% 1/28	0.00% 0/26
Skin and subcutaneous tissue disorders Dermal change lymphedema, phlebolymphedema	3.6% 1/28	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	3.6% 1/28	0.00% 0/26
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils	7.1% 2/28	0.00% 0/26
Nervous system disorders Neuropathy: sensory	3.6% 1/28	3.8% 1/26
Ear and labyrinth disorders Otitis, middle ear (non-infectious)	3.6% 1/28	3.8% 1/26

Additional Information

Dr. Lori Pierce, M.D.

University of Michigan Cancer Center

Phone: 734-764-9922

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place