LBA 25 - Radiotherapy Dose De-Escalation in HPV-Associated Cancers of the Oropharynx Using Metabolic Signature from Interim 18FDG-PET/CT
Presenter(s)
J. R. Robbins1, E. Yu2, P. Shamsesfandabadi3, D. Niedzwiecki4, J. W. C. Lee5, Y. M. Mowery6, Z. Wan4, H. Franklin7, J. P. Kowalski8, A. E. Rodrigues8, Q. Wu5, and D. M. Brizel9; 1Duke University, Duke Cancer Institute, Durham, NC, 2Duke Cancer Center Radiation Oncology, Durham, NC, 3Allegheny Health Network Cancer Institute, Department of Radiation Oncology, Pittsburgh, PA, 4Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 5Duke University Medical Center, Durham, NC, 6Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, 7Duke Cancer Center, Durham, NC, 8Department of Radiation Oncology, Duke Cancer Institute, Durham, NC, 9Department of Head and Neck Surgery and Communication Sciences, Duke University Medical Center, Durham, NC
Purpose/Objective(s): Efforts to de-intensify treatment and reduce toxicity for HPV+ oropharyngeal patients are ongoing and hinge on appropriate patient selection. An early metabolic response on an interim 18FDG-PET/CT may be a viable biomarker for identifying de-escalation candidates. The purpose of this study is to prospectively demonstrate that de-escalated chemoradiotherapy based on early metabolic response will have comparable cancer outcomes and less toxicity than the standard of care.
Materials/Methods: Eligible patients with p16+ squamous cell carcinoma of the oropharynx, stage I-III (AJCC 8th edition), with any smoking history, ECOG score 0-1, and <10% weight loss in the prior 3 month received an initial 18FDG-PET/CT scan at simulation and a second interim 18FDG-PET/CT after receiving 20-24 Gy. Patients who achieved a favorable metabolic response (defined in a previous study as corrected SUVmax <6.7) underwent de-escalation: 60 Gy to gross disease, 36 Gy to elective nodal areas via sequential IMRT boost, and one less cycle of weekly chemotherapy. Those without an adequate response received standard 70 Gy in 35 fractions and 44 Gy elective nodal dose with weekly chemotherapy. FACT-H+N and PRO-CTCAE questionnaires at baseline and at prescribed times during and after treatment assessed toxicity. This study tested the null hypothesis that the 2-year Progression-Free Survival (PFS) in the de-escalation cohort would be within 0.12 of the historical control of 0.92 2-year PFS (H0: 0.92-p = 0.12; HA: 0.92-p < 0.12).
Results: There were 120 evaluable patients. The population included: 56% current/former smokers, 22% N2/N3 disease, and 10% T4 tumors. By stage, 65% stage I, 22% stage II, 13% stage III. 46 patients (38%) met de-escalation criteria. Only T-stage and group stage were significantly associated with the probability of de-escalation on univariate analysis. De-escalation rates were 42% for T0-2, 20% for T3, 17% for T4; 46% for stage I, 31% for stage II, and 13% for stage III. With median follow-up of 1.92 years, the 2-year PFS was 91.6% and 87.1% for the de-escalated and standard groups, respectively. In the de-escalated group, loco-regional control was 100% with 2 distant failure events both at 1.2 years. For the standard group, 7 patients experienced disease recurrence (2 local, 2 regional, and 3 distant). The percentage of patients with dysphagia was lower in the de-escalated group (46% vs 64%) and the grade of dermatitis (grade =2: 30 vs 46%), mucositis (grade 2: 57% vs 62%; grade 3: 9% vs 24%), and xerostomia (grade 2: 28% vs 41%) were also less severe. No grade 4-5 toxicity observed in either group.
Conclusion: 38% met the de-escalation criterion. In preliminary analysis, 2-year PFS was 91.6% among de-escalated patients, above the trial non-inferiority bound with 100% locoregional control. Their toxicity profile was favorable and less severe. Early response on PET CT may be a viable biomarker for selecting de-escalation candidates and warrants further study.