De-intensification of postoperative radiotherapy in head and neck cancer irrespective of human papillomavirus status-results of a prospective multicenter phase II trial (DIREKHT Trial).

Autor:	Haderlein M; Department of Radiotherapy and Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., von der Grün J; Department of Radiotherapy and Radiation Oncology, University Hospital Frankfurt, Goethe-Universitat Frankfurt am Main, Frankfurt am Main, Germany.; Department of Radiation Oncology, Zurich University Hospital, Zurich, Switzerland., Balermpas P; Department of Radiotherapy and Radiation Oncology, University Hospital Frankfurt, Goethe-Universitat Frankfurt am Main, Frankfurt am Main, Germany.; Department of Radiation Oncology, Zurich University Hospital, Zurich, Switzerland., Rödel C; Department of Radiotherapy and Radiation Oncology, University Hospital Frankfurt, Goethe-Universitat Frankfurt am Main, Frankfurt am Main, Germany., Hautmann MG; Department of Radiotherapy and Radiation Oncology, University Hospital of Regensburg, Regensburg, Germany., Steger F; Department of Radiotherapy and Radiation Oncology, University Hospital of Regensburg, Regensburg, Germany., Bohr C; Department of Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany., Hehr T; Department of Radiotherapy and Radiation Oncology, Marienhospital, Stuttgart, Germany., Stromberger C; Department of Radiotherapy and Radiation Oncology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Budach V; Department of Radiotherapy and Radiation Oncology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Schymalla M; Department of Radiotherapy and Radiation Oncology, University Hospital of Marburg, Marburg, Germany., Engenhart-Cabillic R; Department of Radiotherapy and Radiation Oncology, University Hospital of Marburg, Marburg, Germany., Kocik L; Department of Radiation Oncology and Radiotherapy, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria., Geinitz H; Department of Radiation Oncology and Radiotherapy, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria., Nestle U; Department of Radiotherapy and Radiation Oncology, Kliniken Maria Hilf, Moenchengladbach, Germany.; Department of Radiation Oncology, Freiburg University Medical Center, Freiburg, Germany., Klautke G; Department of Radiation Oncology, Chemnitz Hospital, Chemnitz, Germany., Scherl C; Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Gall C; Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Frey B; Department of Radiotherapy and Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Schubert P; Department of Radiotherapy and Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Semrau S; Department of Radiotherapy and Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Ott O; Department of Radiotherapy and Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Kesting M; Department of Oral and Maxillofacial Surgery, University Hospital Erlangen, Erlangen, Germany., Iro H; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Department of Otolaryngology - Head & Neck Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Mueller SK; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Department of Otolaryngology - Head & Neck Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Fietkau R; Department of Radiotherapy and Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2024 Aug 19; Vol. 14, pp. 1447123. Date of Electronic Publication: 2024 Aug 19 (Print Publication: 2024).
DOI:	10.3389/fonc.2024.1447123
Abstrakt:	Background: Current standard treatment concepts in head and neck squamous cell carcinoma (HNSCC) are based on former studies using 2D and 3D treatment plans. However, modern radiation techniques allow for a more precise and individual dose application. Therefore, in a clearly defined patient population, de-intensified risk-adapted radiation is investigated. Methods: Patients with newly diagnosed HNSCC after surgery (with resection margins ≥1 mm and cM0) with the following tumor stages (TNM 7th Edition) were eligible for the study: oral cavity, oropharynx, or larynx: pT1-3, pN0-pN2b; hypopharynx: pT1-2, pN1. The patients should have either a low risk of local recurrence [≤pT2, resection margin ≥5 mm, no peritumoral lymphangiosis (L0), and no perineural invasion] or contralateral lymph node metastasis (≤3 ipsilateral lymph node metastases, in case of well-lateralized oropharyngeal or oral cavity cancer contralateral cN0, otherwise pN0). Patients were assigned to three different treatment regimes with reduction of the treated volume, radiation dose, or both, according to tumor stage and results of surgery performed. The primary objective was to show an LRR of <10% after 2 years. Findings: A total of 150 patients were enrolled. Tumor localizations were as follows: n = 53 (35.3%), oral cavity; n = 94 (62.7%), oropharynx (82% HPV-positive); n = 2 (1.3%), hypopharynx; and n = 1 (0.7%), larynx. A total of 61 patients (41.0%) were stage IVA, 81 (54.0%) were stage III, and 8 (5.3%) were stage II. Median follow-up was 36 months. Cumulative incidence of 2y-LRR was 5.6% (95% CI: 1.7%-9.2%) in the whole study population and 14.1% (95% CI: 3.8%-23.2%) in patients with oral cavity cancer. Cumulative incidence of 2y-LRR in non-irradiated or dose-reduced regions was 3.5% (95% CI: 0.4%-6.5%). After 2 years, disease-free survival was 92% (95% CI: 87%-96%) and overall survival was 94% (95% CI: 90%-98%) for the complete study cohort. Acute III° toxicity was as follows: dysphagia, 30%; xerostomia, 7%; mucositis, 19%; and dermatitis, 4%. Dysphagia and xerostomia decrease over time. After 27 months, late dysphagia III° and xerostomia II° were 1% and 9%, respectively. Interpretation: The study met its primary objective. De-intensification of postoperative radiotherapy irrespective of HPV status in a predefined patient population is associated with a favorable toxicity profile without compromising LRR. In an unplanned subgroup analysis, a significantly increased risk of LRR was observed in patients with oral cavity cancer. In these patients, de-intensified radiotherapy should be applied with caution. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Haderlein, von der Grün, Balermpas, Rödel, Hautmann, Steger, Bohr, Hehr, Stromberger, Budach, Schymalla, Engenhart-Cabillic, Kocik, Geinitz, Nestle, Klautke, Scherl, Gall, Frey, Schubert, Semrau, Ott, Kesting, Iro, Mueller and Fietkau.)
Databáze:	MEDLINE
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