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

Autor: Rosenberg AJ; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA. arirosenberg@medicine.bsd.uchicago.edu., Izumchenko E; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA., Pearson A; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA., Gooi Z; Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL, USA., Blair E; Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL, USA., Karrison T; Department of Public Health Sciences, University of Chicago, Chicago, IL, USA., Juloori A; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA., Ginat D; Department of Radiology, University of Chicago, Chicago, IL, USA., Cipriani N; Department of Pathology, University of Chicago, Chicago, IL, USA., Lingen M; Department of Pathology, University of Chicago, Chicago, IL, USA., Sloane H; Sysmex Inostics, Inc., Baltimore, MD, USA., Edelstein DL; Sysmex Inostics, Inc., Baltimore, MD, USA., Keyser K; Sysmex Inostics GmbH, Hamburg, Germany., Fredebohm J; Sysmex Inostics GmbH, Hamburg, Germany., Holtrup F; Sysmex Inostics GmbH, Hamburg, Germany., Jones FS; Sysmex Inostics, Inc., Baltimore, MD, USA., Haraf D; Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA., Agrawal N; Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, IL, USA., Vokes EE; Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2022 Jan 03; Vol. 22 (1), pp. 17. Date of Electronic Publication: 2022 Jan 03.
DOI: 10.1186/s12885-021-09146-z
Abstrakt: 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.
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.
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.
Trial Registration: This trial is registered with ClinicalTrials.gov on October 1 st , 2020 with Identifier: NCT04572100 .
(© 2021. The Author(s).)
Databáze: MEDLINE
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