3654 - Multicenter Phase III Trial of Chemoradiation (CRT) with IMPT vs. IMRT for Oropharyngeal Squamous Cell Carcinoma (OPSCC): Secondary Analysis of Association of Lymphopenia with Treatment Modality, Emer

A. Grippin¹, R. L. Foote², P. M. Busse³, D. I. Rosenthal⁴, M. Hernandez⁵, A. S. Garden⁴, E. M. Sturgis⁶, R. Ferrarotto⁴, G. B. Gunn⁴, S. H. Patel⁷, N. Y. Lee⁸, A. Lin⁹, J. W. Snider III¹⁰, M. W. McDonald¹¹, C. Henson¹², G. K. Bajaj¹³, N. S. Kalman¹⁴, U. Parvathaneni¹⁵, and S. J. Frank⁴; ¹Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ²Department of Radiation Oncology, Mayo Clinic, Rochester, MN, ³Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, ⁴The University of Texas MD Anderson Cancer Center, Houston, TX, ⁵MD Anderson, Houston, TX, ⁶Baylor College of Medicine, Houston, TX, ⁷Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, ⁸Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁹Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, ¹⁰South Florida Proton Therapy Institute, Delary Beach, FL, ¹¹Emory Proton Therapy Center, Atlanta, GA, ¹²University of Oklahoma Health Sciences Center, OKLAHOMA CITY, OK, ¹³University of Maryland Medical Center, Baltimore, MD, ¹⁴Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, ¹⁵Department of Radiation Oncology, University of Washington/ Fred Hutchinson Cancer Center, Seattle, WA

Purpose/Objective(s): Radiation induced lymphopenia (RIL) is common, but its clinical implications are not well defined. In this secondary analysis of a phase III randomized controlled trial evaluating chemoradiation strategies of intensity modulated proton therapy (IMPT) vs IMRT in patients with advanced stage OPSCC (NCT01893307), we evaluated predictors and clinical implications of RIL. Materials/

Methods: This is a multi-center, randomized, Phase III non-inferiority trial including OPSCC AJCC 7^th stage III-IVA,B, CRT, bilateral neck radiation, and ECOG <3. On-treatment absolute lymphocyte count (ALC) nadir was used to calculate the CTCAE v5 grade of lymphopenia. Covariates including patient characteristics, treatment modality - IMPT vs IMRT, and clinical features were assessed using ANOVA and linear regression with ALC as the dependent variable via per protocol analysis. Covariates demonstrating significant (p<0.05) associations with ALC nadir were selectively introduced in the multivariable analysis (MVA) after being assessed for multicollinearity.

Results: Three hundred ninety seven of 440 patients from 21 institutions initially assigned patients completed CRT, of whom 338 patients had ALC data evaluable for analysis. The majority experienced Grade 3 (n=213, 63%) or Grade 4 (n=75, 22%) lymphopenia. Lymphopenia grade was significantly associated with both ER visits (p<0.001) and hospital admission (p<0.001). Patients who developed Grade 4 lymphopenia presented to the ER 100% more frequently (0.78, 95% CI 0.55-1.0 vs 0.38, 95% CI 0.29-0.49, p<0.001) and were admitted 70% more frequently (0.51, 95% CI 0.35-0.70 vs 0.30, 95% CI 0.21-0.35 p=0.001) than those who did not. At a median follow-up of 3.1 years, there was no statistically significant relationship between lymphopenia and 3-year PFS or OS. On univariate analysis, treatment with IMPT was associated with a 68% lower incidence of Grade 4 lymphopenia (11% vs 34%, p<0.001) and a 28% higher ALC nadir (0.32 vs 0.25, p<0.001). ALC nadir was also strongly correlated with baseline ALC (r² = 0.44, p<0.001), and weakly correlated with CRT (r² = 0.045, p=0.032), body mean dose (r² = 0.045, p<0.001), CTV70 (r² = 0.041, p<0.001), and V5Gy (r² = 0.062, p<0.001). MVA (p<0.001) confirmed significant effects of treatment modality (ß1 = -0.091, p<0.001), baseline ALC (ß2 = 0.14, p<0.001), and CRT with cetuximab (ß4 = 0.12, pp=0.011) and carboplatin (ß5 = 0.10, p=0.039).

Conclusion: In patients with OPSCC treated with CRT, IMPT was associated with a reduced severity of RIL, while RIL was associated with increased rates of ER visits and HA.