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Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus-associated oropharyngeal cancer. ​

文献信息 ​

DOI10.3322/caac.21758
PMID36305841
期刊CA: a cancer journal for clinicians
影响因子232.4
JCR 分区Q1
发表年份2023
被引次数22
关键词化疗、减轻治疗强度、人乳头瘤病毒、口腔及口咽肿瘤、放射肿瘤学
文献类型Journal Article, Review, Research Support, N.I.H., Extramural
ISSN0007-9235
页码164-197
期号73(2)
作者Jung Julie Kang, Yao Yu, Linda Chen, Kaveh Zakeri, Daphna Yael Gelblum, Sean Matthew McBride, Nadeem Riaz, C Jillian Tsai, Anuja Kriplani, Tony K W Hung, James V Fetten, Lara A Dunn, Alan L Ho, Jay O Boyle, Ian S Ganly, Bhuvanesh Singh, Eric J Sherman, David G Pfister, Richard J Wong, Nancy Y Lee

一句话小结 ​

本研究综述了美国人类乳头状瘤病毒（HPV）阳性口咽癌的减轻治疗策略，指出尽管化疗减轻可能影响治疗结果但并未降低毒性，且对经口机器人手术（TORS）的毒性和疗效存在担忧。作者强调需整合多学科数据以优化治疗方案，并建议未来减轻治疗应结合个性化医学和实时反应评估，以提高患者的治疗效果。

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化疗 · 减轻治疗强度 · 人乳头瘤病毒 · 口腔及口咽肿瘤 · 放射肿瘤学

摘要 ​

在美国，由人类乳头状瘤病毒（HPV）感染引起的最常见癌症是口咽癌（OPC），自本世纪初以来，其发病率持续上升。由于化学放疗带来的显著长期疾病负担以及HPV阳性OPC的良好预后，确定该人群的最佳减轻治疗策略已成为过去十年学术头颈外科、放射肿瘤学和医学肿瘤学的关键所在。然而，第一代随机化化疗减轻试验未能改变标准治疗，引发了对减轻治疗可行性的担忧。国家数据库研究估计，约三分之一的患者接受非标准的减轻治疗，而这些治疗具有特定的亚专业细微差别。对多学科减轻治疗数据和当前治疗标准的综合分析对于肿瘤学界强化最佳实践并确保患者获得最佳结果至关重要。在本综述中，作者对前瞻性的HPV阳性OPC减轻治疗试验进行了总结和比较。化疗减轻会影响结果而不降低毒性。有限的数据比较经口机器人手术（TORS）与放疗，令人对TORS的毒性和结果产生担忧。支持在TORS后减轻辅助治疗的前景数据令人鼓舞，但对治疗指征的共识仍然需要。已经报告了一些鼓励性的放射减轻策略（如前期剂量减少和基于诱导化疗的患者选择），但一级证据仍需数年才能获得。最终，仅凭阶段和HPV状态可能不足以指导减轻治疗的实施。减轻治疗的未来可能在于结合治疗内反应评估，以利用个性化医学的优势并整合实时监测。

英文摘要 ​

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

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主要研究问题 ​

  1. 在HPV相关的口咽癌治疗中，如何评估不同患者对去强化治疗策略的反应？
  2. 目前有哪些新的临床试验正在进行，以评估去强化治疗对HPV阳性口咽癌患者的长期效果？
  3. 在选择去强化治疗方案时，除了HPV状态外，还有哪些生物标志物或临床特征应考虑？
  4. 现有的去强化治疗策略中，哪些方法被认为最有潜力在减少毒性同时保持疗效？
  5. 在多学科团队中，如何确保不同专科医生在去强化治疗中的意见达成一致，以优化患者治疗方案？

核心洞察 ​

研究背景和目的 ​

人乳头瘤病毒（HPV）感染引起的最常见癌症是口咽癌（OPC），其发病率自21世纪初以来持续上升。由于化疗和放疗带来的长期病痛以及HPV阳性OPC的良好预后，寻找这一人群的最佳减轻治疗策略已成为头颈外科、放射肿瘤学和医学肿瘤学领域的重要研究方向。尽管首批随机化化疗减轻治疗的试验未能改变标准治疗方案，但仍需关注减轻治疗的可行性。

主要方法/材料/实验设计 ​

本综述整合了多学科的减轻治疗数据及当前治疗标准，以促进肿瘤学界的最佳实践。主要研究方法包括对前瞻性HPV阳性OPC减轻治疗试验的总结和比较。以下是研究的技术路线：

Mermaid diagram

关键结果和发现 ​

  • 化疗减轻策略未能改善患者预后，反而可能影响治疗结果而不降低毒性。
  • TORS与放疗的比较数据有限，且存在毒性和结果方面的担忧。
  • 有支持在TORS后减少辅助治疗的初步数据，但对治疗指征尚需达成共识。
  • 有希望的放疗减轻策略包括前期剂量减少和基于诱导化疗的患者选择，但缺乏I级证据支持。

主要结论/意义/创新性 ​

研究表明，单纯依赖肿瘤分期和HPV状态可能不足以指导减轻治疗的决策。未来的减轻治疗可能需要结合治疗过程中的反应评估，以利用个性化医学的优势并整合实时监测。这一研究为临床实践提供了重要的参考，并指出了未来研究的方向。

研究局限性和未来方向 ​

  • 当前数据主要来自于小规模研究，缺乏大规模、随机对照试验的支持。
  • 未来的研究应关注如何有效整合个体化治疗与实时监测，以优化减轻治疗策略。
  • 需进一步探讨不同治疗方案对不同患者群体的适用性，以确保最佳治疗效果。

参考文献 ​

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  3. Randomized phase-III-trial of concurrent chemoradiation for locally advanced head and neck cancer comparing dose reduced radiotherapy with paclitaxel/cisplatin to standard radiotherapy with fluorouracil/cisplatin: The PacCis-trial. - Rainer Fietkau;Markus Hecht;Benjamin Hofner;Dorota Lubgan;Heinrich Iro;Olaf Gefeller;Claus Rödel;Matthias G Hautmann;Oliver Kölbl;Attila Salay;Christian Rübe;Patrick Melchior;Peter Breinl;Waldemar Krings;Stephan Gripp;Barbara Wollenberg;Rainer Keerl;Ulrike Schreck;Birgit Siekmeyer;Gerhard G Grabenbauer;Panagiotis Balermpas; - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (2020)
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引用本文的文献 ​

  1. Development of a Novel Anti-CD44 Variant 7/8 Monoclonal Antibody, C44Mab-34, for Multiple Applications against Oral Carcinomas. - Hiroyuki Suzuki;Kazuki Ozawa;Tomohiro Tanaka;Mika K Kaneko;Yukinari Kato - Biomedicines (2023)
  2. Prognostic values of systemic inflammation and nutrition-based prognostic indices in oropharyngeal carcinoma. - Tsunehiro Oka;Fumihiko Sato;Takeharu Ono;Toshihiko Kawaguchi;Kenta Murotani;Shintaro Sueyoshi;Taikai Kuroiwa;Takashi Kurita;Mioko Fukahori;Toshiyuki Mitsuhashi;Kiminobu Sato;Shun-Ichi Chitose;Hirohito Umeno - Laryngoscope investigative otolaryngology (2023)
  3. Concurrent carboplatin and paclitaxel definitive radiation therapy for locally advanced head and neck cancer. - James Han;Kaveh Zakeri;Gabriel Raab;Jennifer Hesse;Achraf Shamseddine;Linda Chen;Yao Yu;Jung Julie Kang;Sean M McBride;Nadeem Riaz;C Jillian Tsai;Daphna Gelblum;Eric J Sherman;Richard J Wong;Loren Michel;Nancy Y Lee - Head & neck (2023)
  4. Review of RM-1929 Near-Infrared Photoimmunotherapy Clinical Efficacy for Unresectable and/or Recurrent Head and Neck Squamous Cell Carcinoma. - Nanami L Miyazaki;Aki Furusawa;Peter L Choyke;Hisataka Kobayashi - Cancers (2023)
  5. Neoadjuvant chemoimmunotherapy shows major pathological response and low recurrence in head and neck squamous cell carcinoma. - Shida Yan;Lili Liu;Xing Zhang;Lijun Wei;Wenmei Jiang;Xianlu Gao;Ankui Yang;Xuekui Liu;Wenkuan Chen;Yanfeng Chen;Hui Li;Qiaohong Lin;Menghua Li;Jingtao Chen;Quan Zhang;Shuwei Chen;Ming Song - Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (2024)
  6. A Radiomics-Based Machine Learning Perspective on the Parotid Gland as a Potential Surrogate Marker for HPV in Oropharyngeal Cancer. - Gordian Prasse;Agnes Glaas;Hans-Jonas Meyer;Veit Zebralla;Andreas Dietz;Kathrin Hering;Thomas Kuhnt;Timm Denecke - Cancers (2023)
  7. Tongue electrical impedance myography correlates with functional, neurophysiologic, and clinical outcome measures in long-term oropharyngeal cancer survivors with and without hypoglossal neuropathy: An exploratory study. - Nathan J Hansen;Karin Woodman;Sheila Buoy;Shitong Mao;Carly E A Barbon;Stephen Y Lai;C David Fuller;Katherine A Hutcheson;Benjamin Sanchez - Head & neck (2024)
  8. Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma. - Nancy Y Lee;Eric J Sherman;HeiKo Schöder;Rick Wray;Jay O Boyle;Bhuvanesh Singh;Milan Grkovski;Ramesh Paudyal;Louise Cunningham;Zhigang Zhang;Vaios Hatzoglou;Nora Katabi;Bill H Diplas;James Han;Brandon S Imber;Khoi Pham;Yao Yu;Kaveh Zakeri;Sean M McBride;Jung J Kang;C Jillian Tsai;Linda C Chen;Daphna Y Gelblum;Jatin P Shah;Ian Ganly;Marc A Cohen;Jennifer R Cracchiolo;Luc G T Morris;Lara A Dunn;Loren S Michel;James V Fetten;Anuja Kripani;David G Pfister;Alan L Ho;Amita Shukla-Dave;John L Humm;Simon N Powell;Bob T Li;Jorge S Reis-Filho;Luis A Diaz;Richard J Wong;Nadeem Riaz - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2024)
  9. The role of surgery and deescalation for HPV-related oropharyngeal cancer. - Kevin J Contrera;Mihir R Patel;Barbara Burtness;Ranee Mehra;Robert L Ferris - Cancer (2025)
  10. "Why am I still suffering?": Experience of long-term fatigue and neurocognitive changes in oropharyngeal cancer survivors following (chemo)radiotherapy. - Zsuzsanna Iyizoba-Ebozue;Emma Nicklin;James Price;Robin Prestwich;Sarah Brown;Emma Hall;John Lilley;Matthew Lowe;David J Thomson;Finbar Slevin;Louise Murray;Florien Boele - Technical innovations & patient support in radiation oncology (2024)

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