3492 - UMCC 2023.006: A Pilot Phase II Trial of Individualized FDG-PET and DCE-MRI Directed Adaptive RT in HPV-related Stage III Oropharynx Cancer
Presenter(s)
L. Higgins1, K. Suresh1, J. L. Shah1, B. Nasser1, K. Casper2, M. E. Prince2, D. Forner2, M. Buchakjian2, M. E. Heft-Neal2, P. Yalamanchi2, B. S. Rosen1, A. Shuman2, C. L. Stucken2, C. Brenner3, N. D'Silva4, P. L. Swiecicki5, F. Worden5, and M. L. Mierzwa1; 1Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 2Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, 3University of Michigan, Ann Arbor, MI, 4Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI, 5Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI
Purpose/Objective(s): Adaptive physiologic MRI boost has been demonstrated to improve locoregional control in locally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC). This pilot study measured the incidence of grade 3+ and grade 4+ toxicities with adaptive RT boost incorporating persistently hypermetabolic disease (PHD) on FDG-PET or low blood volume (LBV) on DCE-MRI.
Materials/Methods: Eligible patients had AJCC 8th Edition Stage III p16+ OPSCC planned for definitive chemoradiation. DCE-MRI and FDG PET were acquired at baseline and fraction (fx) 10 with an additional FDG-PET acquired at fx 20. Patients were planned to receive 70 Gy to PTVhigh and 56 Gy to PTVlow in 35 fx, with RT boost starting at fx 15 to PHD (SUV >3) and LBV subvolumes at 2.5 Gy / day. PHD subvolumes were modified following fx 20 PET and boost volumes adjusted starting with fraction 23. Total boost dose was 80 Gy (86 Gy EQD2) with D0.01cc limited to <70 Gy for mucosa, mandible or hyoid. Proportions of in field toxicity events are reported with 95% CIs calculated using the exact (Clopper-Pearson) method.
Results: Of 20 enrolled patients, all were male with a median age of 65; 95% white, 75% never smokers, 18 (90%) had T4 disease and 2 (10%) had N3 disease with median GTVtotal of 95.1 mL (IQR 57.9 - 190.0 mL). Boost volumes comprised 21.69% of GTVp and 0% of GTVn with minimal overlap between PHD and LBV subvolumes. Median follow up for living patients is 16 months. Incidence of acute and long-term toxicities are included in Table 1. One patient with locally recurrent disease was excluded from long-term toxicity analysis. Three patients with T4 disease had a significant hemorrhage, which was fatal in two cases. Both fatal cases occurred in the setting of unclear disease status and baseline major artery involvement.
Conclusion: Multimodality boost was feasible for patients with Stage III HPV+ OPSCC with expected acute and late toxicity. Patients with large volume HPV+ OPSCC involving lingual artery at baseline may be at high risk for fatal hemorrhage and prophylactic embolization should be considered.
Table 1. Acute and Late Toxicities.
| Acute toxicities (≤90 days) | N (%, 95% Confidence interval) | Late Toxicities (>90 days) | N (%, 95% Confidence interval) |
| Inpatient Hospitalization | 2 (10%, 1.2-32%) | Pain requiring narcotics | 5 (26%, 9.1-51%) |
| Interrupted chemotherapy | 3 (15%, 3.2-38%) | Feeding tube | 2 (11%,1.3-33%) |
| Feeding tube | 7 (35%, 15-59%) | Soft tissue necrosis managed medically | 3 (16%, 3.4-40%) |
| Pain requiring long-acting narcotics | 10 (50%, 27-73%) | Lymphedema requiring referral to PT/OT | 12 (63%, 38-84%) |
| RT Delay (≥2 days) | 3 (15%, 3.2-38%) | Fatal Oral Hemorrhage | 2 (11%, 1.3-33%) |
| Dehydration requiring IVF | 3 (15%, 3.2-38%) | Non-fatal oral hemorrhage requiring embolization | 1 (5.3%, 0.13-26%) |
| Grade 3+ mucositis | 1 (5%, 0.13-25%) | ||
| Grade 3+ dermatitis | 0 (0%, 0.00-17%) | ||
| Any Grade 3+ toxicity | 10 (50%, 27-73%) |