{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T16:19:08Z","timestamp":1758039548290,"version":"3.44.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"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:sec><jats:title>Background<\/jats:title><jats:p>The optimal adjuvant therapy for oral squamous cell carcinoma (SCC) patients achieving pathological complete response (pCR) after neoadjuvant immunochemotherapy (NAIC) remains uncertain. While radiotherapy (RT) and chemoradiotherapy (CRT) improve locoregional control, their comparative efficacy and toxicity profiles in this setting are poorly defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Oral SCC patients with pCR post-NAIC were retrospectively enrolled and stratified into RT and CRT groups. Propensity score matching balanced baseline characteristics. Outcomes included 3-year locoregional control (LRC), overall survival (OS), and toxicity. Subgroup analyses evaluated treatment effects by radiologic extranodal extension (rENE) and tumor differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 116 patients analyzed (84 matched), CRT showed no significant LRC or OS benefit over RT alone in the overall cohort (LRC: HR 1.89, 95% CI 0.26\u20134.72, p=0.625; OS: HR 1.45, 95% CI 0.62\u20133.41, p=0.392). However, subgroup analyses revealed CRT improved outcomes in high-risk patients (rENE+ or poorly differentiated tumors), reducing recurrence by 50% (rENE+: HR 3.12, 95% CI 1.13\u20138.60, p=0.028; poor differentiation: HR 3.45, 95% CI 1.23\u20139.68, p=0.019) and enhancing 3-year OS (rENE+: 62.4% <jats:italic>vs<\/jats:italic>. 50.1%, p=0.036; poorly differentiated: 68.3% <jats:italic>vs<\/jats:italic> 53.8%, HR 2.88, p=0.022). CRT was associated with significantly higher acute and chronic toxicities (Grade 3\u20135 mucositis: 36.0% <jats:italic>vs<\/jats:italic>. 12.1%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CRT should be reserved for high-risk pCR patients (rENE+ or poorly differentiated tumors), while RT alone suffices for low-risk cases. This risk-adapted approach optimizes outcomes while minimizing toxicity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1647606","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:12:19Z","timestamp":1757563939000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["De-escalating adjuvant therapy after pathologic complete response in oral squamous cell carcinoma: Chemoradiotherapy benefits only high-risk subgroups"],"prefix":"10.3389","volume":"15","author":[{"given":"Yanjie","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunli","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"113917","DOI":"10.1016\/j.intimp.2024.113917","article-title":"The ending is not the end: Lymph node metastasis in oral squamous cell carcinoma","volume":"146","author":"Wei","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"862","DOI":"10.3390\/cancers17050862","article-title":"The oncological outcome of postoperative radiotherapy in patients with node-negative early-stage (T1\/T2\/N0) oral squamous cell carcinoma and perineural invasion: A meta-analysis","volume":"17","author":"Rao","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.01.003","article-title":"Squamous cell cancers of the aero-upper digestive tract: A unified perspective on biology, genetics, and therapy","volume":"43","author":"Henick","year":"2025","journal-title":"Cancer Cell"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.43.8820","article-title":"Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma","volume":"31","author":"Zhong","year":"2013","journal-title":"J Clin Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00179","article-title":"Prospective phase II open-label randomized controlled trial to compare mandibular preservation in upfront surgery with neoadjuvant chemotherapy followed by surgery in operable oral cavity cancer","volume":"40","author":"Chaukar","year":"2022","journal-title":"J Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"100309","DOI":"10.1016\/j.esmoop.2021.100309","article-title":"Pan-Asian adaptation of the EHNS-ESMO-ESTRO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with squamous cell carcinoma of the head and neck","volume":"6","author":"Keam","year":"2021","journal-title":"ESMO Open"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-0666","article-title":"Neoadjuvant chemoimmunotherapy for the treatment of locally advanced head and neck squamous cell carcinoma: A single-arm phase 2 clinical trial","volume":"28","author":"Zhang","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1038\/s41467-024-46444-z","article-title":"Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial","volume":"15","author":"Wu","year":"2024","journal-title":"Nat Commun"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0000000000000700","article-title":"Immunotherapy for head and neck cancer: from recurrent\/metastatic disease to (neo)adjuvant treatment in surgically resectable tumors","volume":"29","author":"Specenier","year":"2021","journal-title":"Curr Opin Otolaryngol Head Neck Surg"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21758","article-title":"Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus-associated oropharyngeal cancer","volume":"73","author":"Kang","year":"2023","journal-title":"CA Cancer J Clin"},{"key":"B11","doi-asserted-by":"publisher","first-page":"104688","DOI":"10.1016\/j.canrad.2025.104688","article-title":"Breast cancer tumour board: Which patients are eligible for radiotherapy de-escalation or omission","volume":"29","author":"Hibon","year":"2025","journal-title":"Cancer Radiother"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/jso.28071","article-title":"Evidence-based de-escalation of radiotherapy in locally advanced rectal cancer","volume":"131","author":"Ballal","year":"2025","journal-title":"J Surg Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1571285","article-title":"Oncologic outcomes following neoadjuvant immunochemotherapy in locally advanced oral squamous cell carcinoma","volume":"16","author":"Li","year":"2025","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"110050","DOI":"10.1016\/j.radonc.2023.110050","article-title":"Radiologic extranodal extension for nodal staging in nasopharyngeal carcinoma","volume":"191","author":"Ai","year":"2024","journal-title":"Radiother Oncol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"110881","DOI":"10.1016\/j.radonc.2025.110881","article-title":"Impact of the Common Terminology Criteria for Adverse Events (CTCAE) evolution on toxicity scoring in gynaecological radiotherapy","volume":"207","author":"Spampinato","year":"2025","journal-title":"Radiother Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000000489","article-title":"Neoadjuvant immunochemotherapy for locally advanced resectable oral squamous cell carcinoma: a prospective single-arm trial (Illuminate Trial)","volume":"109","author":"Huang","year":"2023","journal-title":"Int J Surg"},{"key":"B17","doi-asserted-by":"publisher","first-page":"102669","DOI":"10.1016\/j.ctrv.2023.102669","article-title":"Neoadjuvant therapy in hormone Receptor-Positive\/HER2-Negative breast cancer","volume":"123","author":"Cantini","year":"2024","journal-title":"Cancer Treat Rev"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.7076","article-title":"Pathologic complete response in patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A systematic review and meta-analysis","volume":"13","author":"Gaber","year":"2024","journal-title":"Cancer Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-021-03915-9","article-title":"Current evidence regarding the role of adjuvant chemotherapy in rectal cancer patients with pathologic complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis","volume":"36","author":"Baloyiannis","year":"2021","journal-title":"Int J Colorectal Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2024.01.024","article-title":"The emerging role of immunotherapy in resectable non-small cell lung cancer","volume":"118","author":"Dunne","year":"2024","journal-title":"Ann Thorac Surg"},{"key":"B21","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/s11934-025-01264-6","article-title":"Management of patients with muscle-invasive bladder cancer achieving A clinical complete response after neoadjuvant therapy: evidence and consideration for active surveillance","volume":"26","author":"Joffe","year":"2025","journal-title":"Curr Urol Rep"},{"key":"B22","doi-asserted-by":"publisher","first-page":"102820","DOI":"10.1016\/j.ctrv.2024.102820","article-title":"Pathologic complete response in patients with localized soft tissue sarcoma treated with neoadjuvant therapy and its correlation with clinical outcomes: A systematic review","volume":"130","author":"Boulouta","year":"2024","journal-title":"Cancer Treat Rev"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032641","article-title":"Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer","volume":"350","author":"Bernier","year":"2004","journal-title":"N Engl J Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032646","article-title":"Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck","volume":"350","author":"Cooper","year":"2004","journal-title":"N Engl J Med"},{"key":"B25","doi-asserted-by":"publisher","first-page":"JCO2017762518","DOI":"10.1200\/JCO.2017.76.2518","article-title":"Improved outcome by adding concurrent chemotherapy to cetuximab and radiotherapy for locally advanced head and neck carcinomas: results of the GORTEC 2007-01 phase III randomized trial","author":"Tao","year":"2018","journal-title":"J Clin Oncol"},{"key":"B26","doi-asserted-by":"crossref","first-page":"2","DOI":"10.6004\/jnccn.2025.0007","article-title":"NCCN guidelines\u00ae Insights: head and neck cancers, version 2.2025","volume":"23","author":"Colevas","year":"2025","journal-title":"J Natl Compr Canc Netw"},{"key":"B27","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/S0140-6736(18)32752-1","article-title":"Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial","volume":"393","author":"Mehanna","year":"2019","journal-title":"Lancet"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.77.0941","article-title":"Postoperative concurrent chemoradiotherapy versus postoperative radiotherapy in high-risk cutaneous squamous cell carcinoma of the head and neck: the randomized phase III TROG 05.01 trial","volume":"36","author":"Porceddu","year":"2018","journal-title":"J Clin Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2406070","article-title":"Survival with trastuzumab emtansine in residual HER2-positive breast cancer","volume":"392","author":"Geyer","year":"2025","journal-title":"N Engl J Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.3390\/medicina60081340","article-title":"Perspectives in using multiple flaps reconstructions for advanced head and neck tumors (Scoping review)","volume":"60","author":"C\u00eerstea","year":"2024","journal-title":"Medicina (Kaunas)"},{"key":"B31","article-title":"Nasopharyngeal carcinoma \u2013 analysis of risk factors and immunological markers","volume":"107","author":"Anghel","year":"2012","journal-title":"Chirurgia (Bucur)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.semradonc.2025.01.003","article-title":"Personalising nasopharyngeal cancer: systemic therapy and radiotherapy treatment volumes","volume":"35","author":"Huang","year":"2025","journal-title":"Semin Radiat Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1647606\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:12:19Z","timestamp":1757563939000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1647606\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":32,"alternative-id":["10.3389\/fonc.2025.1647606"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1647606","relation":{},"ISSN":["2234-943X"],"issn-type":[{"type":"electronic","value":"2234-943X"}],"subject":[],"published":{"date-parts":[[2025,9,11]]},"article-number":"1647606"}}