{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:08:15Z","timestamp":1789391295077,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Squamous cell carcinoma (SCC) of the lip occupies an ambiguous position between cutaneous and oral-cavity oncology and lacks dedicated radiotherapy guidelines, resulting in considerable practice variability. We systematically reviewed the reported radiotherapy practices, clinical outcomes and gaps in consensus at this site. Methods: Following PRISMA 2020 and prospectively registered in PROSPERO (CRD420261349994), we searched PubMed\/MEDLINE, Scopus, the Cochrane Library (Trials) and ClinicalTrials.gov (20 March 2026). Studies of at least ten patients with lip SCC treated with external beam radiotherapy or brachytherapy were eligible. Risk of bias was assessed with ROBINS-I; the synthesis was narrative, following the Synthesis Without Meta-analysis (SWiM) reporting framework. Results: Nine studies (approximately 3904 patients; 1964\u20132021; six countries) met the criteria. Interstitial brachytherapy was the dominant modality (seven studies), with high local control (approximately 93\u201397% in modern actuarial series), favourable toxicity and good functional\/aesthetic outcomes; external beam radiotherapy served mainly as adjuvant treatment. Doses, fractionation, nodal management and outcome reporting were markedly heterogeneous, and eight of nine studies were at serious risk of bias. Conclusions: Radiotherapy\u2014in the identified literature, in effect, largely historical interstitial brachytherapy\u2014appears to be an effective, organ-preserving option in early-stage lip SCC; no conclusions can be drawn for modern external beam techniques such as IMRT. The limited, brachytherapy-dominated evidence warrants cautious interpretation and justifies protocol standardisation, a core outcome set with validated quality-of-life instruments, and multi-institutional prospective registries.<\/jats:p>","DOI":"10.3390\/jcm15187090","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"7090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Radiotherapy in Squamous Cell Carcinoma of the Lip: A Systematic Review of Reported Practices, Clinical Outcomes, and Gaps in Consensus"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3382-9604","authenticated-orcid":false,"given":"Oana","family":"Ciob\u0103nescu","sequence":"first","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"},{"name":"Department of Radiotherapy, University Emergency County Clinical Hospital Craiova, 200642 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anda Elena","family":"Cri\u0219an","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, University Emergency County Clinical Hospital Craiova, 200642 Craiova, Romania"},{"name":"Department of Oncology and Radiotherapy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u0103zvan Marian","family":"B\u0103lan","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"},{"name":"Department of Radiotherapy, University Emergency County Clinical Hospital Craiova, 200642 Craiova, Romania"},{"name":"SC SPAD Imaging International SRL Center, 200352 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virgil","family":"P\u0103tra\u0219cu","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrada-Nemesis","family":"Cri\u0219an","sequence":"additional","affiliation":[{"name":"CM Galaxy Med SRL Craiova, 200377 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana-Iulia","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u0103d\u0103lin-Cristian","family":"Moraru","sequence":"additional","affiliation":[{"name":"Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"},{"name":"SC SPAD Imaging International SRL Center, 200352 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana","family":"M\u0103ce\u0219","sequence":"additional","affiliation":[{"name":"SC SPAD Imaging International SRL Center, 200352 Craiova, Romania"},{"name":"Department of Radiology and Medical Imaging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Popescu","sequence":"additional","affiliation":[{"name":"SC SPAD Imaging International SRL Center, 200352 Craiova, Romania"},{"name":"Department of Radiology and Medical Imaging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"SC SPAD Imaging International SRL Center, 200352 Craiova, Romania"},{"name":"Department of Radiology and Medical Imaging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2024). Global Cancer Observatory: Cancer Today, International Agency for Research on Cancer. Available online: https:\/\/gco.iarc.who.int\/today."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4230","DOI":"10.1038\/s41598-025-88684-z","article-title":"Socio-demographic disparities in global trends of lip and oral cavity neoplasms from 1990 to 2021","volume":"15","author":"Ghanem","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_3","first-page":"caac.70048","article-title":"Global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2022","volume":"76","author":"Rumgay","year":"2026","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e70957","DOI":"10.1002\/cam4.70957","article-title":"Global burden of lip and oral cavity cancer from 1990 to 2021 and projection to 2040: Findings from the 2021 Global Burden of Disease Study","volume":"14","author":"Chen","year":"2025","journal-title":"Cancer Med."},{"key":"ref_5","first-page":"1543","article-title":"Lip cancer: A 10-year retrospective epidemiological study","volume":"32","author":"Maruccia","year":"2012","journal-title":"Anticancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3892\/ol.2022.13594","article-title":"Treatment outcomes of squamous cell carcinoma of the lip: A retrospective study","volume":"25","author":"Babu","year":"2023","journal-title":"Oncol. Lett."},{"key":"ref_7","unstructured":"National Comprehensive Cancer Network (NCCN) (2026, March 20). NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers, Version 1.2026. Available online: https:\/\/www.nccn.org\/guidelines\/category_1."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1016\/j.annonc.2020.07.011","article-title":"Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS\u2013ESMO\u2013ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Machiels","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1111\/odi.14723","article-title":"Long-term outcomes, quality of life, and costs of treatment modalities for T1\u2013T2 lip carcinomas","volume":"30","author":"Wakkee","year":"2024","journal-title":"Oral Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s00066-023-02184-5","article-title":"Can interventional radiotherapy (brachytherapy) be an alternative to surgery in early-stage oral cavity cancer? A systematic review","volume":"200","author":"Draghini","year":"2024","journal-title":"Strahlenther. Onkol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1046\/j.1445-2197.2003.t01-1-02710.x","article-title":"Squamous cell carcinoma of the lip: Is there a role for adjuvant radiotherapy in improving local control following incomplete or inadequate excision?","volume":"73","author":"Babington","year":"2003","journal-title":"ANZ J. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1056\/NEJMoa032641","article-title":"Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer (EORTC 22931)","volume":"350","author":"Bernier","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1056\/NEJMoa032646","article-title":"Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck (RTOG 9501)","volume":"350","author":"Cooper","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1002\/hed.20279","article-title":"Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (#9501)","volume":"27","author":"Bernier","year":"2005","journal-title":"Head Neck"},{"key":"ref_15","unstructured":"Amin, M.B., Edge, S.B., Greene, F.L., Byrd, D.R., Brookland, R.K., Washington, M.K., Gershenwald, J.E., Compton, C.C., Hess, K.R., and Sullivan, D.C. (2017). AJCC Cancer Staging Manual, Springer. [8th ed.]."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"GBD 2019 Lip, Oral, and Pharyngeal Cancer Collaborators, da Cunha, A.R., Compton, K., Xu, R., Mishra, R., Drangsholt, M.T., Antunes, J.L.F., Kerr, A.R., Acheson, A.R., and Lu, D. (2023). The global, regional, and national burden of adult lip, oral, and pharyngeal cancer in 204 countries and territories: GBD 2019. JAMA Oncol., 9, 1401\u20131416.","DOI":"10.1001\/jamaoncol.2023.2960"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.radonc.2009.01.005","article-title":"GEC-ESTRO recommendations for brachytherapy for head and neck squamous cell carcinomas","volume":"91","author":"Mazeron","year":"2009","journal-title":"Radiother. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan\u2014A web and mobile app for systematic reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"i4919","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"l6890","DOI":"10.1136\/bmj.l6890","article-title":"Synthesis without meta-analysis (SWiM) in systematic reviews: Reporting guideline","volume":"368","author":"Campbell","year":"2020","journal-title":"BMJ"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"El Ayachy, R., Sun, R., Ka, K., Laville, A., Duhamel, A.-S., Tailleur, A., Dumas, I., Bockel, S., Espenel, S., and Blanchard, P. (2021). Pulsed dose rate brachytherapy of lip carcinoma: Clinical outcome and quality of life analysis. Cancers, 13.","DOI":"10.3390\/cancers13061387"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"65","DOI":"10.5114\/jcb.2011.23199","article-title":"Long-term results of PDR brachytherapy for lip cancer","volume":"3","author":"Johansson","year":"2011","journal-title":"J. Contemp. Brachytherapy"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e839","DOI":"10.1016\/j.ijrobp.2010.10.031","article-title":"Brachytherapy in lip carcinoma: Long-term results","volume":"81","author":"Guibert","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1002\/(SICI)1097-0347(199909)21:6<526::AID-HED5>3.0.CO;2-B","article-title":"A comparison of results after radiotherapy and surgery for stage I squamous cell carcinoma of the lower lip","volume":"21","author":"Botke","year":"1999","journal-title":"Head Neck"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/1097-0142(197903)43:3<1073::AID-CNCR2820430343>3.0.CO;2-8","article-title":"The place of interstitial therapy using 192-iridium in the management of carcinoma of the lip","volume":"43","author":"Pigneux","year":"1979","journal-title":"Cancer"},{"key":"ref_27","first-page":"666","article-title":"Conference of cancer of the lip (based on a series of 3166 cases)","volume":"90","author":"Stoddart","year":"1964","journal-title":"Can. Med. Assoc. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/0300891621996805","article-title":"Retrospective analysis of outcome and toxicity after postoperative radiotherapy in patients with squamous cell carcinoma of the lip","volume":"108","author":"Lang","year":"2022","journal-title":"Tumori"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.otorri.2015.12.003","article-title":"High dose rate brachytherapy in early stage squamous-cell carcinoma of the lip","volume":"67","author":"Mut","year":"2016","journal-title":"Acta Otorrinolaringol. Esp."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.radonc.2010.12.014","article-title":"Brachytherapy with permanent gold grain seeds for squamous cell carcinoma of the lip","volume":"98","author":"Lock","year":"2011","journal-title":"Radiother. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.radonc.2016.10.008","article-title":"GEC-ESTRO ACROP recommendations for head & neck brachytherapy in squamous cell carcinomas: 1st update","volume":"122","author":"Budrukkar","year":"2017","journal-title":"Radiother. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.radonc.2018.01.013","article-title":"GEC-ESTRO ACROP recommendations in skin brachytherapy","volume":"126","author":"Guinot","year":"2018","journal-title":"Radiother. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.radonc.2017.12.029","article-title":"Skin CanceR Brachytherapy vs. External beam radiation therapy (SCRiBE) meta-analysis","volume":"126","author":"Zaorsky","year":"2018","journal-title":"Radiother. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.ijrobp.2011.09.038","article-title":"High dose-rate versus low dose-rate brachytherapy for lip cancer","volume":"83","author":"Ghadjar","year":"2012","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1001\/archotol.1994.01880310005001","article-title":"Use of decision analysis in planning a management strategy for the stage N0 neck","volume":"120","author":"Weiss","year":"1994","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.radonc.2009.04.014","article-title":"Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients","volume":"92","author":"Pignon","year":"2009","journal-title":"Radiother. Oncol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7090\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:49:10Z","timestamp":1789390150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,12]]},"references-count":36,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15187090"],"URL":"https:\/\/doi.org\/10.3390\/jcm15187090","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,12]]}}}