3413 - Radiation De-Escalation for Human Papillomavirus Negative Oropharyngeal Cancer and Laryngeal/Hypopharyngeal Cancers: Primary Outcomes of a Pilot Study
Presenter(s)
Z. Abou Yehia1, J. J. Kang2, K. Zakeri3, D. Y. Gelblum1, A. Shamseddine1, W. Wong4, A. Kriplani4, S. M. McBride1, L. G. Morris5, B. Givi6, M. Cohen5, J. Cracchiolo5, L. Dunn7, J. Ma1, Y. Yu1, N. Riaz1, A. Ho7, R. J. Wong5, E. Sherman4, and N. Y. Lee1; 1Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 2Yale University Department of Radiation Oncology, New Haven, CT, 3South Sacramento Cancer Center, Sacramento, CA, 4Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 5Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 6Department of Surgery, Head and Neck Service, Memorial Sloan Kettering Cancer Center, New York, NY, 7Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s): Concurrent chemoradiation (CRT) to 70 Gy remains the standard of care for locally advanced head and neck cancer (HNC), achieving high cure rates but at the cost of substantial acute and long-term toxicity. Building on our successful de-escalation efforts in HPV+ OPC, we propose extending a biologically guided radiation therapy (RT) de-escalation strategy to patients with HPV negative HNC. We aim to selectively reduce radiation dose to hypoxia-negative involved lymph nodes (LN) identified by 18F-FMISO PET imaging. We hypothesize that, among patients with hypoxia-negative LN, treatment to 50 Gy will achieve response rates comparable to standard-of-care therapy while reducing treatment-related toxicity.
Materials/Methods: This pilot study planned to accrue 10 patients with T0-T3 N1-2c HPV negative OPC or unknown primary, and laryngeal/hypopharyngeal cancers. Radiation dose to the grossly involved LN with no evidence of hypoxia on 18F-FMISO PET scan is de-escalated to 50 Gy with standard concurrent chemotherapy (high dose cisplatin or carboplatin/5-fluorouracil), while the primary tumor receives 70 Gy. Pilot efficacy is achieved if there are at least 8 of the first 10 evaluable patients who are alive, followed, and have complete response on post-treatment PET/CT. We report here the initial results of the primary outcome of the study. At the time of presentation, all 10 patients will have at least 4 months of follow-up, allowing us to report outcomes for the complete cohort.
Results: 10 patients were enrolled between 2/23 and 7/25. Median age was 63 years (range, 33-85). Seven patients had laryngeal primaries (4 supraglottic, 3 glottic), 2 patients had Tonsillar primaries, and one had a cancer of unknown primary. Five patients (50%) had = T3 disease and six (60%) had N2 disease. Of the 10 patients, 8 had completed at least four months of follow-up with post-treatment imaging and were evaluable for this report. Six of the 8 patients had no evidence of nodal hypoxia on the 18F-FMISO PET and underwent RT de-escalation to 50 Gy to gross nodal disease. Two of the 8 patients demonstrated hypoxia in both the primary tumor and involved lymph nodes and were treated with SOC CRT to 70 Gy. Among de-escalated patients, 5 of 6 (83%) achieved a complete radiographic response on initial post-treatment PET/CT at 3–4 months; and all 6 (100%) subsequently demonstrated complete response. At a median follow-up of 23 months (range, 4-30), all de-escalated patients remained without evidence of disease. Functional status was preserved relative to baseline. No patient developed dysphagia, and all maintained vocal function, with no greater than grade 1 hoarseness.
Conclusion: This is the first study evaluating hypoxia-guided radiation de-escalation in patients with HPV negative HNC. De-escalation of radiation to 50 Gy in hypoxia-negative grossly involved nodes demonstrated promising pilot efficacy and this pilot provides the foundation for larger prospective validation.