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Adjuvant Radiation Therapy for Clinical Stage III Melanoma in the Modern Therapeutic Era

  • Melanoma
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Abstract

Background

Adjuvant radiation therapy (RT) can decrease lymph node basin (LNB) recurrences in patients with clinically evident melanoma lymph node (LN) metastases following lymphadenectomy, but its role in the era of modern systemic therapies (ST), immune checkpoint or BRAF/MEK inhibitors, is unclear.

Patients and Methods

Patients at four institutions who underwent lymphadenectomy (1/1/2010–12/31/2019) for clinically evident melanoma LN metastases and received neoadjuvant and/or adjuvant ST with RT, or ST alone, but met indications for RT, were identified. Comparisons were made between ST alone and ST/RT groups. The primary outcome was 3-year cumulative incidence (CI) of LNB recurrence. Secondary outcomes included 3-year incidences of in-transit/distant recurrence and survival estimates.

Results

Of 98 patients, 76 received ST alone and 22 received ST/RT. Median follow-up time for patients alive at last follow-up was 44.6 months. The ST/RT group had fewer inguinal node metastases (ST 36.8% versus ST/RT 9.1%; P = 0.04), and more extranodal extension (ST 50% versus ST/RT 77.3%; P = 0.02) and positive lymphadenectomy margins (ST 2.6% versus ST/RT 13.6%; P = 0.04). The 3-year CI of LNB recurrences was lower for the ST/RT group compared with the ST group (13.9% versus 25.2%), but this reduction was not statistically significant (P = 0.36). Groups did not differ significantly in in-transit/distant recurrences (P = 0.24), disease-free survival (P = 0.14), or melanoma-specific survival (P = 0.20).

Conclusions

In the era of modern ST, RT may still have value in reducing LNB recurrences in melanoma with clinical LN metastases. Further research should focus on whether select patient populations derive benefit from combination therapy, and optimizing indications for RT following neoadjuvant ST.

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Funding

No external funding was received for this study.

Author information

Author notes

  1. Richard J. Straker and Yun Song contributed equally to this study as lead authors. John N. Lukens and Giorgos C. Karakousis contributed equally to this study as senior authors.

Authors and Affiliations

  1. Department of Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

    Richard J. Straker III MD, Yun Song MD, Adrienne B. Shannon MD & Giorgos C. Karakousis MD

  2. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA

    James Sun MD, Leah S. Cohen MD, Elnara Muradova MD, Hala Daou MD, Vernon K. Sondak MD & Jonathan S. Zager MD

  3. Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Kate Krause MD, Siming Li MD, Dennie T. Frederick MD & Genevieve M. Boland MD, Ph.D.

  4. Department of Surgery, Duke University, Durham, NC, USA

    Kristen E. Rhodin MD & Georgia M. Beasley MD, MHS

  5. Department of Radiation Oncology, Duke University, Durham, NC, USA

    David M. Brizel MD

  6. Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA

    Evan J. Wuthrick MD

  7. Department of Radiation Oncology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA

    Alexander Lin MD & John N. Lukens MD

Authors
  1. Richard J. Straker III MD
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Contributions

Authors responsible for statistical analyses: RJS, MD and YS, MD (same as lead authors). Conception and design of the study: Straker, Song, Lukens, Karakousis. Acquisition of data: Straker, Song, Sun, Krause, Cohen, Muradova, Daou, Frederick, Lee. Analysis and interpretation of data: Straker, Song, Shannon, Krause, Boland, Beasley, Sondak, Wuthrick, Zager, Lin, Lukens, Karakousis. Drafting and critically revising the manuscript: Straker, Song, Sun, Shannon, Krause, Cohen, Muradova, Daou, Frederick, Lee, Boland, Beasley, Sondak, Wuthrick, Krause, Boland, Zager, Lin, Lukens, Karakousis.

Corresponding author

Correspondence to Richard J. Straker III MD.

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Disclosure

Dr. Sondak reports personal fees from Array, Bristol Myers Squibb, Genentech, Merck, Novartis, Pfizer, Regeneron, and Replimune, outside the submitted work. Dr. Wuthrick reports personal fees from Varian and Sanofi, outside the submitted work. Dr. Zager reports advisory board participation with Merck, Amgen, and Sanofi Regeneron; speakers bureau participation with Array Biopharma and Sun Pharma; and research work with Amgen, Provectus, Castle Biosciences, and Delcath Systems, all outside the submitted work. Dr. Boland has sponsored research agreements with Palleon Pharmaceuticals and Olink Proteomics. She served on scientific advisory boards for Nektar Therapeutics and Novartis. She has received honoraria from Novartis and Takeda Pharmaceutics. She served as a consultant to Northwest Biotherapeutics. Dr. Georgia Beasley reports relevant financial activities outside the submitted work as a member of the 2020 Regeneron Sanofi advisory board. Other authors declare no conflicts of interest.

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Straker, R.J., Song, Y., Sun, J. et al. Adjuvant Radiation Therapy for Clinical Stage III Melanoma in the Modern Therapeutic Era. Ann Surg Oncol 28, 3512–3521 (2021). https://doi.org/10.1245/s10434-020-09384-8

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