Trial Outcomes & Findings for Cosmetic Result/Toxicity in Post-Mastectomy Immediate Reconstruction Expander+RT (NCT NCT01664091)

NCT ID: NCT01664091

Last Updated: 2019-08-26

Results Overview

Success rate was defined as the percentage of participants experiencing all of the following: 1) completion of PMRT and placement of the permanent implant and/or flap reconstruction; 2) no major complications (infection requiring hospitalization, major revisions, early/severe capsular contracture, or pain requiring implant removal); and 3) a physician-reported 'excellent' or 'good' cosmetic result (not 'fair' or 'poor') at 2 years following PMRT (requiring a stable reconstruction with good symmetry and contour relative to the contralateral breast).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 32 participants
• Primary outcome timeframe: 2 years
• Results posted on: 2019-08-26

Participant Flow

Participants enrolled from September 2009 through September 2012.

Participant milestones

Measure	TE-ADM With PMRT Participants received immediate breast reconstruction using a sub-muscular tissue expander (TE) and acellular dermal matrix (ADM) sling placed during the same surgery. This was followed by post-mastectomy radiation therapy (PMRT) no sooner than a minimum of 6 weeks and optimally 6 months, if adjuvant chemotherapy was required. The prescribed chest-wall dose was 50 -50.4 gray (Gy) in 25-28 fractions given once daily over 5-7 weeks with a 0.5-centimeter (cm) bolus to the scar every other day. Permanent reconstruction was performed at least 6 months after completion of PMRT.
Overall Study STARTED	32
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	TE-ADM With PMRT Participants received immediate breast reconstruction using a sub-muscular tissue expander (TE) and acellular dermal matrix (ADM) sling placed during the same surgery. This was followed by post-mastectomy radiation therapy (PMRT) no sooner than a minimum of 6 weeks and optimally 6 months, if adjuvant chemotherapy was required. The prescribed chest-wall dose was 50 -50.4 gray (Gy) in 25-28 fractions given once daily over 5-7 weeks with a 0.5-centimeter (cm) bolus to the scar every other day. Permanent reconstruction was performed at least 6 months after completion of PMRT.
Overall Study Death	1
Overall Study Disease Progression	2
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Cosmetic Result/Toxicity in Post-Mastectomy Immediate Reconstruction Expander+RT

Baseline characteristics by cohort

Measure	Tissue Expander and Acellular Dermal Matrix n=32 Participants immediate reconstruction with a TE and ADM followed by PMRT radiation: The prescribed chest-wall dose will be 50 - 50.4 Gy in 25-28 fractions, given once daily over 5-7 weeks.
Age, Continuous	42.3 years n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Breast Cancer Laterality Left	15 Participants n=5 Participants
Breast Cancer Laterality Right	17 Participants n=5 Participants
Mastectomy (unilateral, bilateral) Unilateral	18 Participants n=5 Participants
Mastectomy (unilateral, bilateral) Bilateral	14 Participants n=5 Participants
Number of Lymph Nodes Excised	11 lymph nodes n=5 Participants
Number of Lymph Nodes Involved	2 lymph nodes n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Population: The analysis population is comprised of the evaluable subset of participants with complete 2 year follow-up data.

Success rate was defined as the percentage of participants experiencing all of the following: 1) completion of PMRT and placement of the permanent implant and/or flap reconstruction; 2) no major complications (infection requiring hospitalization, major revisions, early/severe capsular contracture, or pain requiring implant removal); and 3) a physician-reported 'excellent' or 'good' cosmetic result (not 'fair' or 'poor') at 2 years following PMRT (requiring a stable reconstruction with good symmetry and contour relative to the contralateral breast).

Outcome measures

Measure

TE-ADM With PMRT n=26 Participants Participants received immediate breast reconstruction using a sub-muscular tissue expander (TE) and acellular dermal matrix (ADM) sling placed during the same surgery. This was followed by post-mastectomy radiation therapy (PMRT) no sooner than a minimum of 6 weeks and optimally 6 months, if adjuvant chemotherapy was required. The prescribed chest-wall dose was 50 -50.4 gray (Gy) in 25-28 fractions given once daily over 5-7 weeks with a 0.5-centimeter (cm) bolus to the scar every other day. Permanent reconstruction was performed at least 5 months after completion of PMRT.

Success Rate

65.4 percentage of participants Interval 44.3 to 82.8

SECONDARY outcome

Timeframe: Lung dose-volume was measured at the end of radiation therapy which was up to 11 weeks from enrollment in this study cohort.

Population: The analysis population is comprised of all enrolled participants.

Lung dose-volumes were assessed as a percentage of the ipsilateral lung irradiated via dose-volume histograms.

Outcome measures

Measure

TE-ADM With PMRT n=32 Participants Participants received immediate breast reconstruction using a sub-muscular tissue expander (TE) and acellular dermal matrix (ADM) sling placed during the same surgery. This was followed by post-mastectomy radiation therapy (PMRT) no sooner than a minimum of 6 weeks and optimally 6 months, if adjuvant chemotherapy was required. The prescribed chest-wall dose was 50 -50.4 gray (Gy) in 25-28 fractions given once daily over 5-7 weeks with a 0.5-centimeter (cm) bolus to the scar every other day. Permanent reconstruction was performed at least 5 months after completion of PMRT.

Lung Dose-Volume

28.7 percentage radiation dose to lung Interval 6.8 to 38.1

SECONDARY outcome

Timeframe: 2 years

Population: The analysis population is comprised of the evaluable subset of participants with complete 2 year follow-up data.

Cosmesis was measured by means of strict photographic analysis using five views (frontal, right and left lateral, and right and left quarter views) and independent assessment of the results by a plastic surgeon or radiation oncologist who has not treated the patient. Cosmetic score was defined in 4 categories: Excellent = treated breast looks essentially the same as the opposite breast; Good = minimal but identifiable result of treatment; Fair = significant effects of radiation therapy noted; Poor = severe normal tissue sequelae.

Outcome measures

Measure	TE-ADM With PMRT n=24 Participants Participants received immediate breast reconstruction using a sub-muscular tissue expander (TE) and acellular dermal matrix (ADM) sling placed during the same surgery. This was followed by post-mastectomy radiation therapy (PMRT) no sooner than a minimum of 6 weeks and optimally 6 months, if adjuvant chemotherapy was required. The prescribed chest-wall dose was 50 -50.4 gray (Gy) in 25-28 fractions given once daily over 5-7 weeks with a 0.5-centimeter (cm) bolus to the scar every other day. Permanent reconstruction was performed at least 5 months after completion of PMRT.
Cosmetic Score Good	17 Participants
Cosmetic Score Fair	5 Participants
Cosmetic Score Poor	0 Participants
Cosmetic Score Excellent	2 Participants

SECONDARY outcome

Timeframe: Assessed up to 2 years post PMRT

Population: The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.

An independent assessment of contracture was conducted by a plastic surgeon or radiation oncologist who had not treated the participant. Photographic analysis incorporated five views (frontal, right and left lateral, and right and left quarter views). Baker classification was used to score the extent of contracture: Class IA-absolutely natural, cannot tell breast was reconstructed; Class IB-soft, but the implant is detectable by physical examination or inspection because of mastectomy; Class II-mildly firm reconstructed breast with an implant that may be visible and detectable by physical examination; Class III-moderately firm reconstructed breast with readily detectable implant, but the result may still be acceptable; or Class IV-severe capsular contracture with an unacceptable aesthetic outcome and/or significant patient symptoms requiring surgical intervention.

Outcome measures

Measure	TE-ADM With PMRT n=31 Participants Participants received immediate breast reconstruction using a sub-muscular tissue expander (TE) and acellular dermal matrix (ADM) sling placed during the same surgery. This was followed by post-mastectomy radiation therapy (PMRT) no sooner than a minimum of 6 weeks and optimally 6 months, if adjuvant chemotherapy was required. The prescribed chest-wall dose was 50 -50.4 gray (Gy) in 25-28 fractions given once daily over 5-7 weeks with a 0.5-centimeter (cm) bolus to the scar every other day. Permanent reconstruction was performed at least 5 months after completion of PMRT.
Baker Classification Peak Score IA	0 Participants
Baker Classification Peak Score IB	1 Participants
Baker Classification Peak Score II	15 Participants
Baker Classification Peak Score III	14 Participants
Baker Classification Peak Score IV	1 Participants

SECONDARY outcome

Timeframe: 2 Years

Population: The analysis population is comprised of the evaluable subset of participants with complete 2 year follow-up data.

An independent assessment of contracture was conducted by a plastic surgeon or radiation oncologist who had not treated the participant. Photographic analysis incorporated five views (frontal, right and left lateral, and right and left quarter views). Baker classification was used to score the extent of contracture: Class IA-absolutely natural, cannot tell breast was reconstructed; Class IB-soft, but the implant is detectable by physical examination or inspection because of mastectomy; Class II-mildly firm reconstructed breast with an implant that may be visible and detectable by physical examination; Class III-moderately firm reconstructed breast with readily detectable implant, but the result may still be acceptable; or Class IV-severe capsular contracture with an unacceptable aesthetic outcome and/or significant patient symptoms requiring surgical intervention.

Outcome measures

Measure	TE-ADM With PMRT n=22 Participants Participants received immediate breast reconstruction using a sub-muscular tissue expander (TE) and acellular dermal matrix (ADM) sling placed during the same surgery. This was followed by post-mastectomy radiation therapy (PMRT) no sooner than a minimum of 6 weeks and optimally 6 months, if adjuvant chemotherapy was required. The prescribed chest-wall dose was 50 -50.4 gray (Gy) in 25-28 fractions given once daily over 5-7 weeks with a 0.5-centimeter (cm) bolus to the scar every other day. Permanent reconstruction was performed at least 5 months after completion of PMRT.
Baker Classification 2-Year Score IA	0 Participants
Baker Classification 2-Year Score IB	8 Participants
Baker Classification 2-Year Score II	7 Participants
Baker Classification 2-Year Score III	7 Participants
Baker Classification 2-Year Score IV	0 Participants

Adverse Events

TE-ADM With PMRT

Serious events: 4 serious events

Other events: 30 other events

Deaths: 1 deaths

Serious adverse events

Measure	TE-ADM With PMRT n=31 participants at risk Participants received immediate breast reconstruction using a sub-muscular tissue expander (TE) and acellular dermal matrix (ADM) sling placed during the same surgery. This was followed by post-mastectomy radiation therapy (PMRT) no sooner than a minimum of 6 weeks and optimally 6 months, if adjuvant chemotherapy was required. The prescribed chest-wall dose was 50 -50.4 gray (Gy) in 25-28 fractions given once daily over 5-7 weeks with a 0.5-centimeter (cm) bolus to the scar every other day. Permanent reconstruction was performed at least 6 months after completion of PMRT.
Skin and subcutaneous tissue disorders Delayed Healing Wound	3.2% 1/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.
Infections and infestations Infection	3.2% 1/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.
Reproductive system and breast disorders Deflation	3.2% 1/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.
Reproductive system and breast disorders Asymmetry	3.2% 1/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.

Other adverse events

Measure	TE-ADM With PMRT n=31 participants at risk Participants received immediate breast reconstruction using a sub-muscular tissue expander (TE) and acellular dermal matrix (ADM) sling placed during the same surgery. This was followed by post-mastectomy radiation therapy (PMRT) no sooner than a minimum of 6 weeks and optimally 6 months, if adjuvant chemotherapy was required. The prescribed chest-wall dose was 50 -50.4 gray (Gy) in 25-28 fractions given once daily over 5-7 weeks with a 0.5-centimeter (cm) bolus to the scar every other day. Permanent reconstruction was performed at least 6 months after completion of PMRT.
Skin and subcutaneous tissue disorders Delayed Healing	3.2% 1/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.
Skin and subcutaneous tissue disorders Skin Ischemia	6.5% 2/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.
Infections and infestations Infection	3.2% 1/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.
Skin and subcutaneous tissue disorders Chronic Drainage	6.5% 2/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.
Musculoskeletal and connective tissue disorders Pain/costochondritis	61.3% 19/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.
Reproductive system and breast disorders Asymmetry	83.9% 26/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.
Skin and subcutaneous tissue disorders Hyperpigmentation	48.4% 15/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.
Reproductive system and breast disorders Deflation	9.7% 3/31 • Specific adverse events (AEs) as listed were evaluated and reported on the follow-up and cosmetic evaluation case report form at 6-, 12-, 18- and 24 months post RT. AEs were graded according to 5 classifications: mild, mild-moderate, moderate, moderate-severe and severe. Serious AEs were defined as AEs with a classification of moderate-severe or severe and other AEs with a classification of mild, mild-moderate or moderate. The analysis population excludes 1 participant lost-to follow-up who left the country immediately following PMRT.

Additional Information

Julia Wong, MD

Dana-Farber Cancer Institute

Phone: 617-632-3591

Email: JWONG@LROC.HARVARD.EDU

Results disclosure agreements

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