De-intensification of therapy in human papillomavirus associated oropharyngeal cancer

• Verfasst von: Patel, Roshal R. [VerfasserIn]
• Verfasst von: Ludmir, Ethan B. [VerfasserIn]
• Verfasst von: Augustyn, Alexander [VerfasserIn]
• Verfasst von: Zaorsky, Nicholas G. [VerfasserIn]
• Verfasst von: Lehrer, Eric J. [VerfasserIn]
• Verfasst von: Ryali, Rohith [VerfasserIn]
• Verfasst von: Trifiletti, Daniel M. [VerfasserIn]
• Verfasst von: Adeberg, Sebastian [VerfasserIn]
• Verfasst von: Amini, Arya [VerfasserIn]
• Verfasst von: Verma, Vivek [VerfasserIn]
• Titel: De-intensification of therapy in human papillomavirus associated oropharyngeal cancer
• Titelzusatz: a systematic review of prospective trials
• Verf.angabe: Roshal R. Patel, Ethan B. Ludmir, Alexander Augustyn, Nicholas G. Zaorsky, Eric J. Lehrer, Rohith Ryali, Daniel M. Trifiletti, Sebastian Adeberg, Arya Amini, Vivek Verma
• E-Jahr: 2020
• Jahr: 09 March 2020
• Umfang: 9 S.
• Fussnoten: Gesehen am 23.04.2020
• Titel Quelle: Enthalten in: Oral oncology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1997
• Jahr Quelle: 2020
• Band/Heft Quelle: 103(2020) Artikel-Nummer 104608, 9 Seiten
• ISSN Quelle: 1879-0593
• DOI: doi:10.1016/j.oraloncology.2020.104608
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: De-escalation
• Sach-SW: De-intensification
• Sach-SW: Head and neck
• Sach-SW: HPV positive
• Sach-SW: Oropharyngeal
• Sach-SW: Radiotherapy
• K10plus-PPN: 1695780116

Abstract

Numerous trials have been launched over the prior decade examining the safety and efficacy of therapy de-escalation in human papillomavirus (HPV)-associated oropharyngeal cancer (OPC). Because no summative assessment of these prospective trials exists to date, we systematically reviewed the outcomes and toxicities associated with therapy de-intensification for this population. PRISMA-guided systematic PubMed searches (along with articles known to the authors and references thereof) were performed for prospective studies reporting clinical outcomes and/or toxicities of de-intensified RT and/or systemic therapy (with or without surgery), exclusively for HPV-associated OPC. Ten prospective studies were analyzed. Performing a meta-analysis was not entirely possible owing to the heterogeneity of treatment paradigms and the lack of >2 studies for most paradigms; however, because just one paradigm (induction chemotherapy followed by reduced-dose RT and/or systemic therapy) had 4 associated articles, an exploratory meta-analysis was conducted for that subset. Two trials of dose-reduced concurrent chemoradiotherapy (60 Gy/weekly cisplatin) demonstrated 3-year distant metastasis-free survival and overall survival (OS) ranging from 91 to 100% and 95%, respectively; acute grade 3+ mucositis and dysphagia occurred in 33-35% and 21-39%, respectively. In the four trials of induction chemotherapy (platinum/taxane-based) followed by dose-reduced RT, 2-year progression-free and OS ranged from 80 to 95% and 83 to 98%, respectively; acute grade 3+ dysphagia, dermatitis, and mucositis ranged from 9 to 15%, 7 to 20%, and 9 to 30% (excluding one outlier), respectively. For these four trials, the exploratory meta-analysis showed a pooled 2-year PFS and OS of 89% (95% confidence interval, 80-96%) and 96% (92-99%). The pooled rates of grade ≥3 dysphagia, dermatitis, and mucositis were 13% (7-19%), 9% (5-14%), and 28% (9-53%). However, there was significant heterogeneity in the 2-year PFS (I2 = 57%, p = 0.07) and grade ≥3 mucositis (I2 90%, p < 0.01). Next, both randomized trials which replaced concurrent tri-weekly cisplatin with weekly cetuximab illustrated superior outcomes with the former. Lastly, two remaining trials (one using functional imaging to guide reduced-dose RT, and another examining reduced-dose postoperative RT) also showed satisfactory outcomes and toxicities. Taken together, dose-reduced chemoradiotherapy (with or without induction chemotherapy for patient/biology selection purposes) seems to be a promising de-escalation strategy for HPV-associated OPC, although replacement of concurrent cisplatin by cetuximab is not recommended. Long-term follow-up is required for firmer conclusions.