Treatment outcomes and radiotherapy deintensification strategies in human papillomavirus-associated tonsil cancer

(2022) 17:209 Lee et al. Radiation Oncology https://doi.org/10.1186/s13014-022-02177-1 Open Access RESEARCH Treatment outcomes and radiotherapy deintensification strategies in human papillomavirus‑associated tonsil cancer Joongyo Lee1, Kangpyo Kim1, Kyung Hwan Kim1, Ki Chang Keum1, Hye Ryun Kim2, Min Hee Hong2, Eun Chang Choi3, Se‑Heon Kim3, Yoon Woo Koh3 and Chang Geol Lee1* Abstract Background: Human papillomavirus (HPV)-positive tonsil cancer has a better prognosis than HPV-negative tonsil cancer. Deintensification strategies to reduce or avoid radiotherapy (RT) for patients with HPV-associated tonsil cancer have been suggested. This study investigated the treatment outcomes of patients with HPV-associated tonsil cancer and suggested RT deintensification strategies. Methods: A cohort of 374 patients with HPV-associated tonsil cancer treated with primary surgery or RT between 2008 and 2020 was retrospectively evaluated. Survival and locoregional control rates after primary surgery or RT were analyzed, and propensity score matching was performed to adjust for clinical factors. Pearson’s chi-square or Fisher’s exact test was used to compare categorical variables, and Student’s t-test was used to compare continuous variables. The Kaplan–Meier method and log-rank test were used to assess overall survival, progression-free survival, and locore‑ gional failure (LRF). Results: No significant differences in survival or LRF were observed between the primary surgery and RT groups. Subgroup analysis was conducted for patients who underwent primary surgery. Advanced pathological N stage, negative contralateral nodes at diagnosis, abutting or positive surgical margins, and no adjuvant RT were independ‑ ent risk factors for LRF. Advanced pathological T stage was an independent risk factor for LRF in patients who under‑ went primary surgery without subsequent adjuvant RT. None of the patients with pathological complete remission (CR) after induction chemotherapy died or experienced LRF. Conclusions: Our study revealed that the outcomes of primary surgery and primary RT in HPV-positive tonsil cancer were similar after adjusting for clinical factors. Primary RT might be considered instead of surgery in patients with advanced pathological T stage. In the case of pathological CR after induction chemotherapy, deintensification for adjuvant RT should be considered. Keywords: Tonsil cancer, Radiotherapy, Human papillomavirus *Correspondence: 1 Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, 50‑1 Yonsei‑Ro, Seodaemun‑Gu, Seoul 03722, Republic of Korea Full list of author information is available at the end of the article Introduction Human papillomavirus (HPV)-positive oropharyngeal cancer accounts for 60–70% of all oropharyngeal cancers [1] and has a better prognosis than HPV-negative oropharyngeal cancer, with a risk of death nearly half that of HPV-negative oropharyngeal cancer [2]. Standard treatments, including radiotherapy (RT), have shown high © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Lee et al. Radiation Oncology (2022) 17:209 local control rates; however, many treatment-related toxicities have been reported [3]. Several deintensification strategies have been suggested to reduce the treatment intensity. RT is used as definitive or adjuvant therapy in patients with HPV-associated oropharyngeal cancer. Deintensification strategies for primary RT that reduce the prescription dose for concurrent chemoradiotherapy (CCRT) [4, 5], sequential RT to patients with a good response after induction chemotherapy [6], and administering RT alone without concurrent chemotherapy [7] produced similar results to standard treatment. Additionally, deintensification strategies for adjuvant RT, such as performing surgery alone without adjuvant RT in low-risk patients [8], reducing the prescription dose [9], or reducing the field of adjuvant RT [10], have been suggested. However, evidence and guidelines for RT deintensification strategies have not yet been established. Among patients with the same type of oropharyngeal cancer, the pathophysiology differs according to tumor subsite. For example, HPV is more often positive in cancers of the tonsil than those at the base of the tongue [11]. Additionally, bilateral or contralateral cervical lymph node (LN) metastasis is more common in HPV-positive cancer at the base of the tongue than that in the tonsils [12]. However, most studies of deintensification strategies for HPV-associated oropharyngeal cancer do not take the subsite into account. Herein, treatments for HPV-associated tonsil cancer are compared, and strategies for deintensification are presented. Outcomes according to treatment modality and deintensification strategies for RT were also investigated. Materials and methods Patient selection We identified 395 patients with histologically proven HPV-associated tonsil cancer in clinical stages T1–4, N0–3 (American Joint Committee on Cancer, 8th Edition), who were treated with primary surgery or RT at our institution between 2008 and 2020. The exclusion criteria were as follows: (1) double primary cancers (n = 7); (2) incomplete RT regimen (n = 8); or (3) no records of RT (n = 6). Finally, 374 patients were included in our cohort. This study was approved by the Institutional Review Board of our University (No. 4-2021-1332). The requirement for informed consent was waived because of the retrospective nature of the study. All procedures were conducted in accordance with the 2000 revision of the Declaration of Helsinki. Treatment modality All patients underwent primary RT or surgery of curative intent, as decided by a multidisciplinary team. Primary Page 2 of 10 RT was performed in patients with locally advanced cancer, older patients, or patients in whom surgical resection was difficult to perform; primary surgery was performed otherwi (...truncated)