Clinical outcomes of multisite moderate to high dose radiotherapy for patients with metastatic melanoma

Abstract

Background and purpose: This study aimed to summarize the clinical outcomes of patients with metastatic melanoma who received high-dose radiation prior to or during systemic therapy at a single academic institution.

Methods: We identified patients with metastatic melanoma who underwent high-dose radiation therapy (HDRT) for extracranial metastases prior to or during systemic therapy from 2010 to 2018. Treatment indications included oligometastases, oligoprogression, and local control. Using the Kaplan-Meier method, we plotted overall survival (OS), progression-free survival-1 (PFS1), and PFS2. Competing risk analysis determined the cumulative incidence of local failure (LF) and the time to start or change systemic therapy (SCST). Univariate and multivariable analyses were used to identify predictive factors.

Results: We analyzed 34 patients with 79 lesions, with a median follow-up of 17.4 months. Sixty-eight percent of patients received systemic therapy after the first HDRT. The median OS was 22 months, with brain metastases before HDRT being a significant predictor in multivariable analysis. The median PFS1 for first-line HDRT was 4.1 months, and the median PFS2 was 3.9 months. Rates of LF were 10.3% at 12 months and 11.7% at 24 months. The incidence of SCST following HDRT was 59.8% at 12 months and 76.1% at 24 months, with radiation targeted at the lung associated with a lower incidence of SCST.

Conclusion: HDRT for treating metastatic lesions in melanoma demonstrated excellent local control and may play a role in delaying SCST. Additional courses of HDRT may provide cumulative benefits.

Keywords

immunotherapy / local control / metastatic melanoma / progression-free survival / radiotherapy

References

[1] ArnoldM, SinghD, LaversanneM, et al. Global burden of cutaneous melanoma in 2020 and projections to 2040. JAMA Dermatol. 2022;158(5):495-503.

[2] Cancer Stat Facts: Melanoma of the Skin. SEER database. NIH. https://seer.cancer.gov/statfacts/html/melan.html

[3] WolchokJD, Chiarion-Sileni V, GonzalezR, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377:1345-1356.

[4] RobertC, LongGV, BradyB, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320-330.

[5] RobertC, Schachter J, LongGV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Eng J Med. 2015;372:2521-2532.

[6] LongGV, Stroyakovskiy D, GogasH, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371:1877-1888.

[7] LarkinJ, Ascierto PA, BrenoB, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371:1867-1876.

[8] DummerR, Ascierto PA, GogasHJ, et al. Encorafenib plus binimetinib versus vermurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19(5):603-615.

[9] LehrerEJ, SinghR, WangM, et al. Safety and survival rates associated with ablative stereotactic radiotherapy for patients with oligometastatic cancer: a systemic review and meta-analysis. JAMA Oncol. 2021;7(1):92-106.

[10] PatelPH, PalmaD, McDonaldF, Tree AC. The dandelion dilemma revisited for oligoprogression: treat the whole lawn or weed selectively?Clin Oncol (R Coll Radiol)2019;31:824-833.

[11] FranceschiniD, Franzese C, De RoseF, et al. Role of extra cranial stereotactic body radiation therapy in the management of stage IV melanoma. Br J Radiol. 2017;90(1077):20170257.

[12] LaraTM, HelouJ, PoonI, et al. Multisite stereotactic body radiotherapy for metastatic non-small-cell lung cancer: delaying the need to start or change systemic therapy?Lung Cancer. 2018;124:219-226.

[13] ThompsonR, CheungP, ChuW, et al. Outcomes of extra-cranial stereotactic body radiotherapy for metastatic colorectal cancer: dose and site of metastases matter. Radiother Oncol. 2020;142:236-245.

[14] TanH, CheungP, LouieAV, et al. Outcomes of extra-cranial stereotactic body radiotherapy for metastatic breast cancer: treatment indication matters. Radiother Oncol. 2021;161:159-165.

[15] SpencerKL, van der Velden JM, WongE, et al. Systemic review of the role of stereotactic radiotherapy for bone metastases. J Natl Cancer Inst. 2019;111:1023-1032.

[16] DoyenJ, PicardA, NaghaviAO, et al. Clinical outcomes of metastatic melanoma treated with checkpoint inhibitors and multisite radiotherapy. JAMA Dermatol. 2017;153(10):1056-1059.

[17] ChandraRA, Wilhite TJ, BalboniTA, et al. A systemic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab. Oncoimmunology. 2015;4(11):e1046028.

[18] AhmedKA, Torres-Roca JF. Stereotactic body radiotherapy in the management of oligometastatic disease. Cancer Control. 2016;23(1):21-29.

[19] PoonI, ErlerD, DaganR, et al. Evaluation of definitive stereotactic body radiotherapy and outcomes in adults with extracranial oligometastasis. JAMA Netw Open. 2020;3(11):e2026312.

[20] PalmaDA, OlsonR, HarrowS, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase II randomized trial. J Clin Oncol. 2020;38(25):2830-2838.

[21] SundahlN, Seremet T, DorpeJV, et al. Phase 2 trial of nivolumab combined with stereotactic body radiation therapy in patients with metastatic or locally advanced inoperable melanoma. Int J Radiat Oncol Biol Phys, 2019;104(4):828-835.

[22] RatnayakeG, Reinwald S, ShackletonM, et al. Stereotactic radiation therapy combined with immunotherapy against metastatic melanoma: long-term results of a phase 1 clinical trial. Int J Radiat Oncol Biol Phys. 2020;108(1):150-156.

[23] CurtiB, Crittenden M, SeungSK, et al. Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma. J Immunother Cancer. 2020;8(1):e000773.

[24] GeY, CheX, GaoX, et al. Combination of radiotherapy and targeted therapy for melanoma brain metastases: a systemic review. Melanoma Res. 2021;31(5):413-420.

[25] FineJP, GrayRJ. A Proportional Hazards Model for the Subdistribution of a Competing Risk. J Am Stat Assoc. 1999;94:496-509.

[26] WeickhardtAJ, Scheier B, BurkeJM, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thor Oncol. 2012;7:1807-1814.

[27] OstP, Reynders D, DecaesteckerK, et al. Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. J Clin Oncol. 2018;36:446-453.

[28] Downs-CannerS, ZenatiM, BooneBA, et al. The indolent nature of pulmonary metastases from ductal adenocarcinoma of the pancreas. J Surg Oncol. 2015;112(1):80-85.

[29] LukeJJ, Rutkowski P, QueiroloP, et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (Keynote-716): a randomized, double-blind, phase 3 trial. Lancet. 2022;399(10336):1718-1729.

[30] NeumanHB, PatelA, HanlonC, et al. Stage-IV melanoma and pulmonary metastases: factors predictive of survival. Ann Surg Oncol. 2007;14(10):2847-2853.

[31] WankhedeD, GroverS. Patients with malignant melanoma: a systemic review and meta-analysis. Ann Surg Oncol. 2022;29(6):3709-3723.

[32] MazzolaR, Fersino S, FerreraG, et al. Stereotactic body radiotherapy for lung oligometastases impacts on systemic treatment-free survival: a cohort study. Med Oncol2018;35(9):121.

RIGHTS & PERMISSIONS

2024 2024 The Authors. Precision Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Shandong Cancer Hospital & Institute.