112 - TRINITY-HPV: Transoral RobotIc surgery (TORS) Followed by deinteNsified Post-OperatIve ChemoradioTherapY (CRT) in HPV-Associated Oropharyngeal Carcinoma (OPC)

03:20pm - 03:30pm ET

Room 162

Presenter(s)

Zachary Zumsteg, MD - Cedars-Sinai Medical Center, Los Angeles, CA

Z. S. Zumsteg¹, M. Luu¹, M. Tighiouart¹, J. Mallen-St. Clair², E. Walgama¹, T. J. Endicott³, A. Schumacher³, B. L. King¹, J. Chang¹, A. Horodner⁴, D. Manzoor⁵, L. Piro⁶, J. Moyers⁷, S. L. Shiao¹, J. K. Jang¹, A. Mita⁸, K. Scher¹, M. M. Chen⁹, and A. S. Ho¹; ¹Cedars-Sinai Medical Center, Los Angeles, CA, ²Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, ³Torrance Memorial Medical Center, Torrance, CA, ⁴The Hunt Cancer Institute at Torrance Memorial Medical Center, Torrance, CA, ⁵Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, ⁶The Angeles Clinic and Research Institute, Los Angeles, CA, ⁷The Angeles Clinic & Research Institute, Los Angeles, CA, ⁸Hoag Hospital, Newport Beach, CA, ⁹Department of Otolaryngology, University of Michigan, Ann Arbor, MI

Purpose/Objective(s): HPV-associated OPC is cured at high rates with standard of care therapy, but deintensified treatment regimens have been unable to produce equivalent outcomes in phase III trials. We hypothesized that TORS followed by substantially dose-reduced CRT would maintain oncologic outcomes with improved quality of life for OPC patients.

Materials/Methods: This was a prospective non-randomized phase II clinical trial enrolling patients with cT0-3N0-2 HPV-associated OPC at two medical centers. Patients underwent TORS followed by deintensified CRT. All patients had standard indications for post-operative RT (pT3, PNI, LVI, close/positive margins, multiple positive lymph nodes [LNs], LNs > 3cm, and/or extranodal extension [ENE]). All patients received 30 Gy in 15 daily fractions with weekly cisplatin (40mg/m2). Those with ENE, positive margins, and/or 5 or more positive LNs received an additional targeted boost of 20 Gy in 10 fractions with cisplatin to the high-risk area only (i.e. site of positive margins or ENE). The primary endpoint was 2-year progression-free survival (PFS). Tumor tissue modified viral DNA (TTMV-DNA) and patient reported outcomes, such as the MD Anderson Dysphagia Index (MDADI, scale: 0-100, 100 = no swallowing issues), Xerostomia Quality of Life Scale (XeQoLS, scale: 0-4, 0 = no xerostomia), Hearing Handicap Inventory for Adults (HHIA, scale: 0-60, 0 = no hearing issues), and PRO-CTCAE were collected.

Results: 55 patients were enrolled, and 54 were analyzable due to 1 patient withdrawing consent. Median age was 60 (range: 34-80), 45 were male (83%) and 15% had a >10 pack-year smoking history. 11% of patients were pN2, 29% had ENE, 17% had positive margins, and 9% had 5 or more positive lymph nodes. 32 patients (59%) received 30 Gy with no boost, and 22 patients (41%) received 30 Gy followed by a boost targeted to high-risk regions. Post-operative TTMV-DNA was undetectable in 31/32 (97%) and 18/22 (82%) patients treated without or with a boost, respectively. All patients completed RT and 89% received all planned cycles of cisplatin. Median follow-up was 2.4 years. 2-year PFS was 98%. 2-year local control, regional control, distant control, and overall survival were 100%, 98%, 100%, and 100%, respectively. One patient required a G-tube and 3 patients were hospitalized during treatment, all in the boost arm. There was no grade 3-5 late toxicity. 24 month post-treatment mean MDADI, XeQOLs, and HHIA scores were 86, 0.43 and 4, respectively, compared to values of 79, 0.37, and 4 at the start of adjuvant CRT.

Conclusion: TORS followed by deintensified cisplatin-based CRT produced excellent oncologic outcomes with limited long-term toxicity. To our knowledge, this is the highest 2-year PFS ever reported with deintensified therapy for HPV-associated OPC despite a marked reduction in radiation dose and >40% patients harboring high-risk pathologic features. This strategy warrants assessment in randomized trials.