3715 - The Impact of Age and Tumor Volume on Volumetric Systemic Therapy Response in HPV-Positive Oropharyngeal HNSCC - A Pooled Analysis of Prospective Trials

G. Rajeev-Kumar¹, M. Arshad², A. J. Rosenberg³, J. Hara⁴, R. R. Katipally⁴, E. A. Blair⁵, E. Izumchenko³, N. Agrawal⁵, A. Pearson¹, D. J. Haraf⁶, E. E. Vokes³, and A. Juloori⁴; ¹University of Chicago, Chicago, IL, ²Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, MI, ³Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, ⁴Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, ⁵Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Chicago, Chicago, IL, ⁶Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, IL

Purpose/Objective(s): Systemic therapy plays a crucial role in the treatment of head and neck squamous cell carcinoma (HNSCC) in both the locoregionally advanced and recurrent/metastatic settings. The MACH-NC analysis demonstrates decreased overall survival benefit for chemotherapy in elderly patients treated definitively with chemoradiotherapy. Whether this is due to the detrimental effect of poor tolerability or a true difference in efficacy has not been well characterized. In order to examine this, we utilized HPV-positive oropharyngeal cancer (OPC) as a model with prospective data from patients enrolled on consecutive iterations of induction chemo- or chemoimmunotherapy (IC) response adaptive de-escalation trials. In addition to age, we hypothesized that body mass index (BMI), statin use, baseline tumor volume, and neutrophil- and platelet-lymphocyte ratios (NLR and PLR) may be potential predictors of response to IC. In order to examine this in a granular fashion, tumor volume was measured pre-and post-induction therapy. Materials/

Methods: Patients with locally advanced HPV+ OPC treated on three phase II institutional trials were included for analysis. In two of the trials, induction chemotherapy comprised of carboplatin (AUC 5 - 6 on day[d] 1) and (nab-)paclitaxel (100 mg/m² on d 1, 8, 15) for three 21-d cycles. In the third trial, nivolumab (360 mg on d1) was added to the prior IC regimen. Primary and nodal tumor volumes were contoured on matched pre-and post IC diagnostic CT/MRI. A multilinear regression (MLR) was performed to evaluate potential predictors of volumetric response in the primary and nodes to IC.
Results: Of 148 evaluable patients, 138 (93%) were males with median age at diagnosis of 63 [56, 68]. The mean BMI was 29.3 (SD=5) and about a third (n=54, 36.7%) were on statins. The median NLR and PLR were 2.45 [1.8, 3.2] and 135 [109, 172] respectively. Median baseline total tumor volume was 27 cm³ [18.7, 38.6]. The median total volumetric change was a reduction by 79.4% [67.8, 86] following IC. MLR demonstrated age as the only significant negative predictor (B = -0.38, p = 0.039) of response to IC. Patients were then divided by the median age of 63. MLR showed the pre-IC volume of the primary (B = -0.19, p = 0.04) to be a significant negative predictor of response to IC in patients younger than 63.
Conclusion: Increased age is an independent predictor of worse volumetric response to systemic chemo(immuno) therapy. The underpinnings of this should be further explored. Furthermore, in the younger cohort, larger primary tumor volume was associated with poorer volumetric response. The role for cytoreductive radiotherapy to improve chemoimmunotherapy outcomes in the recurrent/metastatic setting should be investigated in clinical trials.