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Clinical Trial
. 2024 Apr 1;7(4):e245217.
doi: 10.1001/jamanetworkopen.2024.5217.

Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial

Mark V Schaverien  1 , Puneet Singh  2 , Benjamin D Smith  3 , Wei Qiao  4 , Catherine L Akay  2 , Elizabeth S Bloom  3 , Mariana Chavez-MacGregor  5 , Carrie K Chu  1 , Mark W Clemens  1 , Jessica S Colen  2 , Richard A Ehlers  2 , Rosa F Hwang  2 , Melissa M Joyner  3 , Rene D Largo  1 , Alexander F Mericli  1 , Melissa P Mitchell  3 , John W Shuck  1 , Nina Tamirisa  2 , Debasish Tripathy  5 , Mark T Villa  1 , Wendy A Woodward  2 , Rensi Zacharia  3 , Henry M Kuerer  2 , Karen E Hoffman  3
Affiliations
Clinical Trial

Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial

Mark V Schaverien et al. JAMA Netw Open. .

Abstract

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR).

Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR.

Design, setting, and participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible.

Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI.

Main outcome and measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis.

Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis.

Conclusions and relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678).

Trial registration: ClinicalTrials.gov Identifier: NCT02912312.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Smith reported receiving salary support from Varian Medical Systems; grants from Artidis; and royalty and equity interest from Oncora Medical outside the submitted work. Dr Mericli reported receiving personal fees from Mentor Worldwide LLC, Destiny Pharma PLC, and Allergan Inc outside the submitted work. Dr Mitchell reported receiving personal fees from DAVA Oncology; and grants from ARTIDIS outside the submitted work. Dr Kuerer reported receiving personal fees from NEJM Group Inc, McGraw Hill Professional Inc, and UpToDate Inc outside the submitted work. Dr Hoffman reported receiving grants from Janssen to the institution and grants from Varian Medical Systems to the institution outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. CONSORT Diagram for the Phase 2 Trial of Premastectomy Radiotherapy (PreMRT)
CF indicates conventionally fractionated; HF, hypofractionated; and RT, radiotherapy. aScreening data are unavailable for the time period of the study when the first 20 patients were enrolled.
See this image and copyright information in PMC

Comment in

References

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