{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:14:15Z","timestamp":1786115655361,"version":"build-2736575974"},"reference-count":9,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with limited therapeutic options once it reaches metastatic stages. While immune checkpoint inhibitors like avelumab have improved outcomes, achieving a complete and durable response in stage IV disease remains challenging. We report the case of a 75-year-old male diagnosed with stage IV MCC, negative for Merkel cell polyomavirus (MCPyV) and with 1% PD-L1 tumor cell expression, presenting with a primary tumor in the right thigh, a regional inguinal nodal conglomerate, and a distant mediastinal lymph node metastasis. Initial treatment with first-line avelumab resulted in a discordant response, with a near-complete metabolic response of the mediastinal lesion but persistence of the primary tumor. Localized radiotherapy (RT) \u2014 66 Gy in 33 fractions delivered by intensity-modulated radiotherapy (IMRT), encompassing the primary tumor, the inguinal nodal conglomerate, and at-risk regional nodal basins \u2014 was subsequently added while avelumab was continued. Following completion of RT and the fourteenth cycle of avelumab, a complete metabolic and morphological response was documented by FDG PET-CT across all disease sites, including the non-irradiated mediastinal node, consistent with an abscopal effect. Treatment was reasonably well tolerated, with grade 3 radiodermatitis and grade 1 radiation cystitis as the only reported adverse events, and no immune-related toxicity. The patient has since maintained a durable remission under surveillance with maintenance RT. This case suggests a potent synergistic interaction between avelumab and RT, potentially mediated by an abscopal effect at the non-irradiated distant site. The strategic combination of these therapies may overcome initial resistance to immunotherapy in advanced MCC, highlighting the need for further clinical investigation into radio-immunotherapy protocols for this malignancy.<\/jats:p>","DOI":"10.3389\/fonc.2026.1867799","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:24:16Z","timestamp":1785990256000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Complete metabolic response in stage IV Merkel cell carcinoma after combined avelumab and radiotherapy: a case report suggestive of an abscopal effect"],"prefix":"10.3389","volume":"16","author":[{"given":"Jordi","family":"Guzman-Casta","sequence":"first","affiliation":[{"name":"Oncology Institute of Quer\u00e9taro, Hospital Angeles Centro Sur","place":["Quer\u00e9taro, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Alejandro","family":"Lozano-Valdez","sequence":"additional","affiliation":[{"name":"School of Medicine, An\u00e1huac University Quer\u00e9taro","place":["Quer\u00e9taro, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frida Sophia","family":"Trejo-Mendoza","sequence":"additional","affiliation":[{"name":"School of Medicine, An\u00e1huac University Quer\u00e9taro","place":["Quer\u00e9taro, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Cecilia","family":"Mac\u00edas-Flores","sequence":"additional","affiliation":[{"name":"Radio-Oncology Department, Hospital Angeles Centro Sur","place":["Quer\u00e9taro, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2024.05.013","article-title":"Merkel cell carcinoma","volume":"38","author":"Strong","year":"2024","journal-title":"Hematol Oncol Clin North Am"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2022.07.015","article-title":"Merkel cell carcinoma","volume":"41","author":"Lewis","year":"2023","journal-title":"Dermatol Clin"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-025-01693-z","article-title":"Merkel cell carcinoma: Current treatment landscape and emerging therapeutic targets","volume":"27","author":"Pan","year":"2025","journal-title":"Curr Oncol Rep"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002646","article-title":"First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): Primary and biomarker analyses of a phase II study","volume":"9","author":"D'Angelo","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B5","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s41392-022-01102-y","article-title":"Radiotherapy combined with immunotherapy: The dawn of cancer treatment","volume":"7","author":"Zhang","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B6","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s40425-018-0352-8","article-title":"In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: A case series","volume":"6","author":"Xu","year":"2018","journal-title":"J Immunother Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2019-230518","article-title":"Combined radio-immunotherapy leads to complete clinical regression of stage IV Merkel cell carcinoma","volume":"12","author":"Principe","year":"2019","journal-title":"BMJ Case Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.628324","article-title":"Case report: Exceptional response to avelumab after failure of electrochemotherapy in a patient with rapidly progressive, PD-L1-negative Merkel cell carcinoma","volume":"11","author":"Torchio","year":"2021","journal-title":"Front Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-017-0310-x","article-title":"Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after \u22651 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial","volume":"6","author":"Kaufman","year":"2018","journal-title":"J Immunother Cancer"}],"container-title":["Frontiers in 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