TY - JOUR
T1 - Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer
T2 - Optima paradigm expanded experience
AU - Rosenberg, Ari J.
AU - Agrawal, Nishant
AU - Pearson, Alexander
AU - Gooi, Zhen
AU - Blair, Elizabeth
AU - Cursio, John
AU - Juloori, Aditya
AU - Ginat, Daniel
AU - Howard, Adam
AU - Chin, Jeffrey
AU - Kochanny, Sara
AU - Foster, Corey
AU - Cipriani, Nicole
AU - Lingen, Mark
AU - Izumchenko, Evgeny
AU - Seiwert, Tanguy Y.
AU - Haraf, Daniel
AU - Vokes, Everett E.
N1 - Publisher Copyright:
© 2021
PY - 2021/11
Y1 - 2021/11
N2 - Background: Favorable prognosis for Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) led to investigation of response-adaptive de-escalation, yet long-term outcomes are unknown. We present expanded experience and follow-up of risk/response adaptive treatment de-intensification in HPV+ OPC. Methods: A phase 2 trial (OPTIMA) and subsequent cohort of sequential off-protocol patients treated from September 2014 to November 2018 at the University of Chicago were reviewed. Eligible patients had T3-T4 or N2-3 (AJCC 7th edition) HPV+ OPC. Patients were stratified by risk: High-risk (HR) (T4, ≥N2c, or >10PYH), all others low-risk (LR). Induction chemotherapy (IC) included 3 cycles of carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (off-protocol). LR with ≥50% response received low-dose radiotherapy (RT) alone to 50 Gy (RT50). LR with 30–50% response and HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45 Gy (CRT45). All others received full-dose CRT to 75 Gy (CRT75). Results: 91 patients consented and 90 patients were treated, of which 31% had >10PYH, 34% had T3/4 disease, and 94% had N2b/N2c/N3 disease. 49% were LR and 51% were HR. Overall response rate to induction was 88%. De-escalated treatment was administered to 83%. Median follow-up was 4.2 years. Five-year OS, PFS, LRC, and DC were 90% (95% CI 81,95), 90% (95% CI 80,95), 96% (95% CI 90,99), and 96% (88,99) respectively. G-tube placement rates in RT50, CRT45, and CRT75 were 3%, 33%, and 80% respectively (p < 0.05). Conclusion: Risk/response adaptive de-escalated treatment for an inclusive cohort of HPV+ OPC demonstrates excellent survival with reduced toxicity with long-term follow-up.
AB - Background: Favorable prognosis for Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) led to investigation of response-adaptive de-escalation, yet long-term outcomes are unknown. We present expanded experience and follow-up of risk/response adaptive treatment de-intensification in HPV+ OPC. Methods: A phase 2 trial (OPTIMA) and subsequent cohort of sequential off-protocol patients treated from September 2014 to November 2018 at the University of Chicago were reviewed. Eligible patients had T3-T4 or N2-3 (AJCC 7th edition) HPV+ OPC. Patients were stratified by risk: High-risk (HR) (T4, ≥N2c, or >10PYH), all others low-risk (LR). Induction chemotherapy (IC) included 3 cycles of carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (off-protocol). LR with ≥50% response received low-dose radiotherapy (RT) alone to 50 Gy (RT50). LR with 30–50% response and HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45 Gy (CRT45). All others received full-dose CRT to 75 Gy (CRT75). Results: 91 patients consented and 90 patients were treated, of which 31% had >10PYH, 34% had T3/4 disease, and 94% had N2b/N2c/N3 disease. 49% were LR and 51% were HR. Overall response rate to induction was 88%. De-escalated treatment was administered to 83%. Median follow-up was 4.2 years. Five-year OS, PFS, LRC, and DC were 90% (95% CI 81,95), 90% (95% CI 80,95), 96% (95% CI 90,99), and 96% (88,99) respectively. G-tube placement rates in RT50, CRT45, and CRT75 were 3%, 33%, and 80% respectively (p < 0.05). Conclusion: Risk/response adaptive de-escalated treatment for an inclusive cohort of HPV+ OPC demonstrates excellent survival with reduced toxicity with long-term follow-up.
KW - Chemotherapy
KW - Head and neck cancer
KW - Human papillomavirus
KW - Radiation therapy
KW - Treatment de-intensification
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U2 - 10.1016/j.oraloncology.2021.105566
DO - 10.1016/j.oraloncology.2021.105566
M3 - Article
C2 - 34662771
AN - SCOPUS:85117077966
SN - 1368-8375
VL - 122
JO - Oral Oncology
JF - Oral Oncology
M1 - 105566
ER -