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Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment.

Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment.

Authors :
Rosenberg AJ
Izumchenko E
Pearson A
Gooi Z
Blair E
Karrison T
Juloori A
Ginat D
Cipriani N
Lingen M
Sloane H
Edelstein DL
Keyser K
Fredebohm J
Holtrup F
Jones FS
Haraf D
Agrawal N
Vokes EE
Source :
BMC cancer [BMC Cancer] 2022 Jan 03; Vol. 22 (1), pp. 17. Date of Electronic Publication: 2022 Jan 03.
Publication Year :
2022

Abstract

Background: Human 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.<br />Methods: Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, [Formula: see text] 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.<br />Discussion: A 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.<br />Trial Registration: This trial is registered with ClinicalTrials.gov on October 1 <superscript>st</superscript> , 2020 with Identifier: NCT04572100 .<br /> (© 2021. The Author(s).)

Details

Language :
English
ISSN :
1471-2407
Volume :
22
Issue :
1
Database :
MEDLINE
Journal :
BMC cancer
Publication Type :
Academic Journal
Accession number :
34980038
Full Text :
https://doi.org/10.1186/s12885-021-09146-z