Abstract
BackgroundHuman papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC.MethodsPatients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, ge 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response.DiscussionA de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC.Trial registrationThis trial is registered with ClinicalTrials.gov on October 1st, 2020 with Identifier: NCT04572100.
Highlights
Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment
Clinical trials evaluating combined modality therapy with chemotherapy and radiation treatment have demonstrated a favorable prognosis for HPV + OPC compared with HPV-negative disease, with 3-year overall survival (OS) rates of approximately 80–90%[4,5,6]
Current treatment paradigms for locoregionally advanced HPV + OPC include definitive concomitant chemoradiation or surgical resection followed by adjuvant radiation with or without chemotherapy [7]
Summary
Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Standard combined modality therapy is associated with substantial acute and long-term toxicities This has led to interest in developing a de-intensification treatment paradigm for HPV + OPC that optimizes the therapeutic to toxicity ratio for patients [8, 9]. Strategies to de-escalate treatment for patients with HPV + OPC have included replacing or omitting concurrent chemotherapy [10,11,12], dose or volume reduction of concurrent chemoradiation[13, 14], de-intensified adjuvant therapy[15, 16], and response adaptive de-intensification[9, 17,18,19]. Attempts to de-intensify treatment in randomized phase III trials by reducing or omitting chemotherapy in HPV + OPC resulted in worse survival[10, 11], suggesting that the favorable prognosis is related to the increased sensitivity of HPV + OPC to chemotherapy and radiation therapy [20]
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