Combined Spatial and Dosimetric Recurrence Pattern Analysis in Head and Neck Squamous Cell Carcinoma Following Postoperative (Chemo)radiotherapy

Abstract Background Advancements in nodal staging for head and neck squamous cell carcinoma (HNSCC) have prompted radiotherapy de-escalation trials to reduce irradiation of electively treated neck regions, with the goal of improving treatment tolerability. While volumetric de-escalation has shown pr...

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Main Authors: Philipp Schröter, Hoi Hin Lau, Florian Stritzke, Henrik Franke, Katharina Weusthof, Sebastian Regnery, Lukas Bauer, Maximilian Deng, Katharina Dvornikovich, Anna Hofmann, Lars Wessel, Karl Semmelmayer, Julius Moratin, Oliver Ristow, Jürgen Hoffmann, Peter Plinkert, Gerhard Dyckhoff, Jürgen Debus, Thomas Held
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Radiation Oncology
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Online Access:https://doi.org/10.1186/s13014-025-02641-8
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author Philipp Schröter
Hoi Hin Lau
Florian Stritzke
Henrik Franke
Katharina Weusthof
Sebastian Regnery
Lukas Bauer
Maximilian Deng
Katharina Dvornikovich
Anna Hofmann
Lars Wessel
Karl Semmelmayer
Julius Moratin
Oliver Ristow
Jürgen Hoffmann
Peter Plinkert
Gerhard Dyckhoff
Jürgen Debus
Thomas Held
author_facet Philipp Schröter
Hoi Hin Lau
Florian Stritzke
Henrik Franke
Katharina Weusthof
Sebastian Regnery
Lukas Bauer
Maximilian Deng
Katharina Dvornikovich
Anna Hofmann
Lars Wessel
Karl Semmelmayer
Julius Moratin
Oliver Ristow
Jürgen Hoffmann
Peter Plinkert
Gerhard Dyckhoff
Jürgen Debus
Thomas Held
author_sort Philipp Schröter
collection DOAJ
description Abstract Background Advancements in nodal staging for head and neck squamous cell carcinoma (HNSCC) have prompted radiotherapy de-escalation trials to reduce irradiation of electively treated neck regions, with the goal of improving treatment tolerability. While volumetric de-escalation has shown promise in definitive radiotherapy of HNSCC, limited data exist regarding its safety in the postoperative treatment setting. This study aimed to assess dose-level-specific locoregional recurrence patterns following standard postoperative (chemo)radiotherapy in a mixed HNSCC cohort to inform risk-adaptive radiotherapy strategies. Materials and methods We retrospectively reviewed 203 HNSCC patients (75% HPV-negative, 25% HPV-positive) treated with curative intent postoperative (chemo)radiotherapy from 2017 to 2021. Recurrence imaging was co-registered with planning CT, and recurrent tumor volumes were dosimetrically compared to the target volume dose and spatially analyzed using a center-of-mass-based approach. We classified five recurrence types: A (central high-dose), B (peripheral high-dose), C (central intermediate- or low-dose), D (peripheral intermediate- or low-dose), and E (extraneous dose). Results With a median follow-up of 39.7 months, the three-year local, regional, and distant control of HPV-negative HNSCC were 84%, 87%, and 87%, respectively. Of 56 recurrences, 17 were local, 13 regional, 3 locoregional, 9 combined local/regional with concomitant distant failure, and 14 distant only. Of 40 analyzed recurrences, we identified 47.5% as type A/B, 5% as type C/D intermediate-dose, and 20% as type E, half of which were secondary cancers. Among the 27.5% (11/40) type C/D low-dose recurrences in the elective target volume, 15% (6/40) were true nodal failures, resulting in an overall elective neck failure rate of 3% (6/203). Conclusion The predominance of high-dose recurrences suggests that biological tumor resistance is a key driver of treatment failure, highlighting the necessity to refine postoperative risk stratification and integrate tumor biology into dose escalation decisions. The low incidence of isolated nodal recurrences in electively treated neck regions supports the feasibility of volumetric de-escalation of postoperative radiotherapy. This approach might not only be feasible for HPV-associated oropharyngeal cancers but also for HPV-negative tumors, provided that accurate nodal staging has been conducted.
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spelling doaj-art-5ee57df5b9e6425e8d86e5bd182accfa2025-08-20T02:20:01ZengBMCRadiation Oncology1748-717X2025-04-0120111210.1186/s13014-025-02641-8Combined Spatial and Dosimetric Recurrence Pattern Analysis in Head and Neck Squamous Cell Carcinoma Following Postoperative (Chemo)radiotherapyPhilipp Schröter0Hoi Hin Lau1Florian Stritzke2Henrik Franke3Katharina Weusthof4Sebastian Regnery5Lukas Bauer6Maximilian Deng7Katharina Dvornikovich8Anna Hofmann9Lars Wessel10Karl Semmelmayer11Julius Moratin12Oliver Ristow13Jürgen Hoffmann14Peter Plinkert15Gerhard Dyckhoff16Jürgen Debus17Thomas Held18Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, Heidelberg UniversityDepartment of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, Heidelberg UniversityDepartment of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, Heidelberg UniversityDepartment of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, Heidelberg UniversityDepartment of Otorhinolaryngology, Head and Neck Surgery, Heidelberg University Hospital, Heidelberg UniversityDepartment of Otorhinolaryngology, Head and Neck Surgery, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityDepartment of Radiation Oncology, Heidelberg University Hospital, Heidelberg UniversityAbstract Background Advancements in nodal staging for head and neck squamous cell carcinoma (HNSCC) have prompted radiotherapy de-escalation trials to reduce irradiation of electively treated neck regions, with the goal of improving treatment tolerability. While volumetric de-escalation has shown promise in definitive radiotherapy of HNSCC, limited data exist regarding its safety in the postoperative treatment setting. This study aimed to assess dose-level-specific locoregional recurrence patterns following standard postoperative (chemo)radiotherapy in a mixed HNSCC cohort to inform risk-adaptive radiotherapy strategies. Materials and methods We retrospectively reviewed 203 HNSCC patients (75% HPV-negative, 25% HPV-positive) treated with curative intent postoperative (chemo)radiotherapy from 2017 to 2021. Recurrence imaging was co-registered with planning CT, and recurrent tumor volumes were dosimetrically compared to the target volume dose and spatially analyzed using a center-of-mass-based approach. We classified five recurrence types: A (central high-dose), B (peripheral high-dose), C (central intermediate- or low-dose), D (peripheral intermediate- or low-dose), and E (extraneous dose). Results With a median follow-up of 39.7 months, the three-year local, regional, and distant control of HPV-negative HNSCC were 84%, 87%, and 87%, respectively. Of 56 recurrences, 17 were local, 13 regional, 3 locoregional, 9 combined local/regional with concomitant distant failure, and 14 distant only. Of 40 analyzed recurrences, we identified 47.5% as type A/B, 5% as type C/D intermediate-dose, and 20% as type E, half of which were secondary cancers. Among the 27.5% (11/40) type C/D low-dose recurrences in the elective target volume, 15% (6/40) were true nodal failures, resulting in an overall elective neck failure rate of 3% (6/203). Conclusion The predominance of high-dose recurrences suggests that biological tumor resistance is a key driver of treatment failure, highlighting the necessity to refine postoperative risk stratification and integrate tumor biology into dose escalation decisions. The low incidence of isolated nodal recurrences in electively treated neck regions supports the feasibility of volumetric de-escalation of postoperative radiotherapy. This approach might not only be feasible for HPV-associated oropharyngeal cancers but also for HPV-negative tumors, provided that accurate nodal staging has been conducted.https://doi.org/10.1186/s13014-025-02641-8Recurrence patternsPostoperative radiation therapyOral cavity cancerHead and neck cancerLocal controlDosimetric analysis
spellingShingle Philipp Schröter
Hoi Hin Lau
Florian Stritzke
Henrik Franke
Katharina Weusthof
Sebastian Regnery
Lukas Bauer
Maximilian Deng
Katharina Dvornikovich
Anna Hofmann
Lars Wessel
Karl Semmelmayer
Julius Moratin
Oliver Ristow
Jürgen Hoffmann
Peter Plinkert
Gerhard Dyckhoff
Jürgen Debus
Thomas Held
Combined Spatial and Dosimetric Recurrence Pattern Analysis in Head and Neck Squamous Cell Carcinoma Following Postoperative (Chemo)radiotherapy
Radiation Oncology
Recurrence patterns
Postoperative radiation therapy
Oral cavity cancer
Head and neck cancer
Local control
Dosimetric analysis
title Combined Spatial and Dosimetric Recurrence Pattern Analysis in Head and Neck Squamous Cell Carcinoma Following Postoperative (Chemo)radiotherapy
title_full Combined Spatial and Dosimetric Recurrence Pattern Analysis in Head and Neck Squamous Cell Carcinoma Following Postoperative (Chemo)radiotherapy
title_fullStr Combined Spatial and Dosimetric Recurrence Pattern Analysis in Head and Neck Squamous Cell Carcinoma Following Postoperative (Chemo)radiotherapy
title_full_unstemmed Combined Spatial and Dosimetric Recurrence Pattern Analysis in Head and Neck Squamous Cell Carcinoma Following Postoperative (Chemo)radiotherapy
title_short Combined Spatial and Dosimetric Recurrence Pattern Analysis in Head and Neck Squamous Cell Carcinoma Following Postoperative (Chemo)radiotherapy
title_sort combined spatial and dosimetric recurrence pattern analysis in head and neck squamous cell carcinoma following postoperative chemo radiotherapy
topic Recurrence patterns
Postoperative radiation therapy
Oral cavity cancer
Head and neck cancer
Local control
Dosimetric analysis
url https://doi.org/10.1186/s13014-025-02641-8
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