De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials

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

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Article number104608
JournalOral Oncology
Volume103
DOIs
StatePublished - Apr 2020

Keywords

  • De-escalation
  • De-intensification
  • Head and neck
  • HPV positive
  • Oropharyngeal
  • Radiotherapy

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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