Schröter Philipp, Lau Hoi Hin, Stritzke Florian, Franke Henrik, Weusthof Katharina, Regnery Sebastian, Bauer Lukas, Deng Maximilian, Dvornikovich Katharina, Hofmann Anna, Wessel Lars, Semmelmayer Karl, Moratin Julius, Ristow Oliver, Hoffmann Jürgen, Plinkert Peter, Dyckhoff Gerhard, Debus Jürgen, Held Thomas
Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany.
Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.
Radiat Oncol. 2025 Apr 23;20(1):63. doi: 10.1186/s13014-025-02641-8.
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.
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).
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).
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.
头颈部鳞状细胞癌（HNSCC）区域淋巴结分期的进展促使开展放疗降阶梯试验，以减少对选择性治疗颈部区域的照射，目的是提高治疗耐受性。虽然容积降阶梯在HNSCC的根治性放疗中已显示出前景，但关于其在术后治疗环境中的安全性的数据有限。本研究旨在评估标准术后（化疗）放疗后混合HNSCC队列中特定剂量水平的局部区域复发模式，为风险适应性放疗策略提供依据。
我们回顾性分析了2017年至2021年接受根治性术后（化疗）放疗的203例HNSCC患者（75%人乳头瘤病毒阴性，25%人乳头瘤病毒阳性）。将复发影像与计划CT进行配准，并将复发肿瘤体积与靶体积剂量进行剂量学比较，并使用基于质心的方法进行空间分析。我们将复发类型分为五种：A（中央高剂量）、B（周边高剂量）、C（中央中低剂量）、D（周边中低剂量）和E（额外剂量）。
中位随访39.7个月，人乳头瘤病毒阴性HNSCC的三年局部、区域和远处控制率分别为84%、87%和87%。在56例复发中，17例为局部复发，13例为区域复发，3例为局部区域复发，9例为局部/区域联合远处转移失败，14例仅为远处转移。在40例分析的复发中，我们确定47.5%为A/B型，5%为C/D型中剂量，20%为E型，其中一半为继发性癌症。在选择性靶体积中27.5%（11/40）的C/D型低剂量复发中，15%（6/40）为真正的淋巴结转移失败，导致总体选择性颈部转移失败率为3%（6/203）。
高剂量复发占主导地位表明肿瘤生物学抗性是治疗失败的关键驱动因素，突出了完善术后风险分层并将肿瘤生物学纳入剂量递增决策的必要性。选择性治疗颈部区域孤立性淋巴结复发的低发生率支持术后放疗容积降阶梯的可行性。这种方法不仅对人乳头瘤病毒相关口咽癌可行，对人乳头瘤病毒阴性肿瘤也可行，前提是已进行准确的淋巴结分期。
