110 - Pooled Analysis of Prospective Trials of FMISO PET-Guided 30Gy De-Escalation in HPV-Positive Oropharyngeal Cancer
Presenter(s)
N. Y. Lee1, E. Sherman2, H. Schoder3, E. C. Dee1, N. S. Kalman4, C. E. Rutter5, C. Y. Roque1, C. Y. Bensley1, C. White6, Y. Wu1, Y. Yu1, A. Shamseddine1, K. Zakeri7, L. Chen8, D. Y. Gelblum1, C. J. Tsai9, J. J. Kang10, S. M. McBride1, A. Ho11, R. J. Wong12, and N. Riaz1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 3Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 4Department of Oncological Sciences, Florida International University, Herbert Wertheim College of Medicine, Miami, FL, 5Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT, 6Memorial Sloan-Kettering Cancer Center, New York, NY, 7South Sacramento Cancer Center, Sacramento, CA, 8Department of Radiation Oncology, University of Chicago, Chicago, IL, 9Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada, 10Yale University Department of Radiation Oncology, New Haven, CT, 11Memorial Sloan Kettering Cancer Center, New York, NY, 12Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s):
Major radiation dose de-escalation to 30Gy for biologically selected human papillomavirus–associated oropharyngeal carcinoma (HPV+ OPC) was developed to meaningfully reduce radiation-related toxicity while maintaining oncologic control. We report mature long-term toxicity and survival outcomes from a substantially expanded prospective multicenter phase II cohort.Materials/Methods:
A prespecified integrated analysis of 3 consecutive, prospective trials was conducted that included patients with T0–3/N1–2c HPV+ OPC (10/2015–11/2023) who underwent hypoxia imaging, 18F-fluoromisonidazole positron emission tomography (FMISO PET). Patients with non-hypoxic tumors received chemoradiation (CRT) to 30Gy; intra-treatment hypoxia positive patients received CRT to 70Gy. Patients were concurrently treated with either high dose cisplatin or carboplatin and 5-fluorouracil. Primary endpoint was 5-year overall survival (OS). Secondary endpoints included acute and late RT-related toxicities, patient-reported outcomes (PROS), local, regional, and distant failure, and progression-free survival (PFS). Salvage therapy is also reported.Results:
There were 430 patients where 323 received 30Gy and 107 received 70Gy. With a median follow-up 4.05 years (range 1.27–10.03 years), 5-year OS was 97% in both arms. The majority of both acute and late RT-related toxicity was substantially reduced with 30Gy vs 70Gy (See Table). The 5-year local failure (2.2% vs 1.9%, p=0.7), regional failure (6.2% vs 3.9%, p=0.4), and PFS (91% vs 89%, p=0.5) were similar. Distant failure was higher in patients with intra-treatment hypoxia (7.5% vs 1.3%, p=0.004). In the 30Gy cohort, first failures were local (n=5), regional (n=29), and distant (n=2). Locoregional recurrences were predominantly salvaged with surgery alone (local n=3; regional n=17) or surgery plus CCRT (local n=2; regional n=11), with one regional failure treated with chemo/immunotherapy.Conclusion:
FMISO PET–guided 30Gy de-escalation significantly reduces acute and late radiation-related toxicity, including clinically meaningful decreases in late xerostomia and dysphagia, while preserving durable long-term survival and disease control. Distant failures were higher in patients with intra-treatment hypoxia. This biologically guided strategy is undergoing phase III validation, 118 patients enrolled out of 291 at the time of this submission (NCT06563479). Abstract 110 – Table 1| Toxicity available for 411 patients | 30Gy (n=309) | 70Gy (n=102) | p-value |
| Acute Dermatitis (any) | 53.7% | 86.3% | <0.000001 |
| Acute Dysphagia (any) | 61.2% | 85.3% | <0.00001 |
| Acute Oral Mucositis (any) | 75.4% | 87.3% | 0.012 |
| Acute Xerostomia (any) | 85.1% | 88.2% | 0.51 |
| Acute Dysgeusia (any) | 89.6% | 86.3% | 0.37 |
| Acute Dysphagia (Grade 3) | 0.6% | 3.9% | 0.004 |
| Late Dysgeusia (any) | 74.8% | 80.4% | 0.28 |
| Late Xerostomia (Grade 2) | 2.2% | 10.8% | <0.00089 |
| Late Dysphagia (any) | 7.8% | 39.2% | <0.000001 |