Sep 28

SS 09 - Head and Neck 1: Highest-Rated Abstracts for Virally-Mediated Head and Neck Cancer

154 - The Influence of Chemo-Radiotherapy Dose and Radiotherapy Volumes on Peripheral Immunity in HPV+ Oropharyngeal Cancer

05:05pm - 05:15pm PT

Room 305/306/309

Presenter(s)

Nadeem Riaz, MD, MS - memorial sloan kettering, new york, New York

N. Riaz¹, A. Shamseddine¹, D. Gelblum¹, S. M. McBride¹, Y. Yu¹, L. Chen², K. Zakeri¹, J. J. Kang³, C. J. Tsai⁴, Y. Wu⁵, J. R. Cracchiolo⁶, R. J. Wong⁶, M. Cohen⁶, I. Ganly⁶, L. Dunn⁷, A. Ho⁷, E. Sherman⁷, and N. Y. Lee¹; ¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Memorial Sloan Kettering Cancer Center, New York, NY, ³Yale University, New Haven, CT, ⁴Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, ⁵Memorial Sloan-Kettering Cancer Center, New York, NY, ⁶Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, ⁷Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): Chemoradiotherapy (CRT) is immunosuppressive and combining it with immune-checkpoint blockade concurrently has had limited success. The impact of CRT dose and field size on systemic immunity remains poorly understood. We sought to evaluate the influence of these factors on peripheral blood immune populations in two consecutive de-intensification studies in HPV+ oropharyngeal cancer (OPC).

Materials/Methods: We retrospectively analyzed patients enrolled in two prospective de-intensification studies (MSK-17-409A and 22-215) that modified CRT dose and volume for HPV+ OPC. Eligible patients (AJCC 7^th edition T1–T2, N1–N2c, p16+ and HPV RNA-ISH+) received either 30 Gy with two cycles or 70 Gy with three cycles of bolus chemotherapy, guided by interim [¹⁸F]-FMISO PET/CT findings. Study MSK-17-409A employed elective nodal RT to 30 Gy, whereas MSK-22-215 delivered RT to gross disease only. Complete blood counts with differentials were obtained before therapy, 2 weeks intra-rx, 4 months post-rx, and 2 years post-rx. Changes in absolute or relative blood counts between groups were compared with Wilcoxon-rank sum test. Relative blood counts were derived from pre-rx values.

Results: Of 204 total patients analyzed, 152 received elective RT (128 at 30Gy [30Gy_elective], 24 at 70Gy [70Gy_elective]) and 52 received GTV-only RT (37 at 30Gy [30Gy_GTVonly], 15 at 70Gy [70Gy_GTVonly]). Absolute lymphocyte counts before therapy between 30Gy_elective, 70Gy_elective, 30Gy_GTVonly, and 70Gy_GTVonly were 1.62 (+/- 0.04), 1.68 (+/- 0.12), 1.49 (+/-, 0.08), and 1.72 (+/- 0.19) 10³ cells/ul respectively and did not differ between groups. At two weeks into treatment, patients receiving elective treatment showed greater lymphocyte decline versus GTV-only treatment (54% vs. 41% drop, p<0.001). At four months post-treatment, lymphocyte recovery was higher in GTV-only versus elective treated patients (68% vs 52% of baseline, p < 0.001). Recovery was delayed even comparing 30Gy_elective to 70Gy_GTVonly (66% vs. 54%, p=0.05), where the latter group received an additional cycle of chemotherapy. Patients receiving elective RT had longer follow-up and showed persistently reduced lymphocyte recovery at 2 years between 30Gy vs 70Gy (71% vs 52%, p = 0.005). Elective treatment or duration of treatment did not influence neutrophil or monocyte counts (full data presented at meeting).

Conclusion: Elective nodal RT in HPV+ OPC significantly reduces circulating lymphocyte counts during therapy and leads to slower recovery of counts post treatment, when only 30Gy was given. The decrement to lymphocytes from elective RT is larger than administering an additional cycle of chemotherapy and treating GTV only to 70 Gy. Duration of treatment can influence lymphocyte counts years after treatment. How RT volume and duration influence interactions with treatments that rely on lymphocytes warrants additional study.