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

• Published in: BMC cancer Vol. 22; no. 1; pp. 17 - 8
• Main Authors: Rosenberg, Ari J, Izumchenko, Evgeny, Pearson, Alexander, Gooi, Zhen, Blair, Elizabeth, Karrison, Theodore, Juloori, Aditya, Ginat, Daniel, Cipriani, Nicole, Lingen, Mark, Sloane, Hillary, Edelstein, Daniel L, Keyser, Kirsten, Fredebohm, Johannes, Holtrup, Frank, Jones, Frederick S, Haraf, Daniel, Agrawal, Nishant, Vokes, Everett E
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.01.2022; BioMed Central; BMC
• Subjects: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biomarkers; Biomarkers, Tumor - blood; Cancer; Cancer therapies; Carboplatin; Carboplatin - administration & dosage; Care and treatment; Cell-Free Nucleic Acids - blood; Chemoradiotherapy; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Deoxyribonucleic acid; DNA; DNA, Viral - blood; Drug Monitoring - methods; Feasibility Studies; Female; Genetic aspects; Genomes; Head & neck cancer; Head and neck cancer; Health aspects; Human papillomavirus; Humans; Induction Chemotherapy; Induction therapy; Laboratories; Male; Medical prognosis; Middle Aged; Oropharyngeal cancer; Oropharyngeal Neoplasms - blood; Oropharyngeal Neoplasms - drug therapy; Oropharyngeal Neoplasms - virology; Paclitaxel; Paclitaxel - administration & dosage; Papillomaviridae - genetics; Papillomavirus infections; Papillomavirus Infections - blood; Papillomavirus Infections - virology; Patients; Plasma; Prognosis; Prospective Studies; Quality of life; Radiation therapy; Radiotherapy; Study Protocol; Surveillance; Throat cancer; Toxicity; Treatment de-escalation; Treatment Outcome; Young Adult; United States; Germany; Head and neck cancer; Treatment de-escalation; Chemotherapy; Human papillomavirus; Radiotherapy
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-09146-z

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. 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. 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. This trial is registered with ClinicalTrials.gov on October 1 , 2020 with Identifier: NCT04572100 .