3617 - Whole-Body FDG PET and Occult Gross Residual Disease prior to Adjuvant Chemoradiotherapy in High-Risk HNSCC: Prospective Findings from the Phase II HYPCON-02 Trial
Presenter(s)
A. Sharma1, A. Ramadas2, A. Ghosh1, A. Singhal3, K. Das3, S. Sarswat3, J. Meena4, M. Verma3, R. Kumar3, J. Sharma1, N. Gupta3, S. Panda5, K. Kamboj6, S. Mallick1, S. Bhasker6, and D. N. Sharma7; 1National Cancer Institute, All India Institute of Medical Sciences, New Delhi, India, 2AIl India Institute of Medical Sciences, New Delhi, Delhi, India, 3AIIMS New Delhi, Jhajjar, India, 4National Cancer Institute, AIIMS,Delhi, Jhajjar, India, 5National Cancer Institute, AIIMS-Jhajjar, Jhajjar, India, 6All India Institute of Medical Sciences, New Delhi, India, 7AIl India Institute of Medical Sciences, New Delhi, India
Purpose/Objective(s): Adjuvant concurrent chemoradiotherapy (CRT) is the standard of care for resected high-risk head and neck squamous cell carcinoma (HNSCC). However, patients are presumed to harbor microscopic disease at CRT initiation, and the true incidence of persistent macroscopic disease has never been prospectively evaluated. We incorporated mandatory pre-CRT whole-body FDG PET imaging within the HYPCON-02 phase II trial to quantify occult gross residual disease and evaluate whether conventional high-risk pathologic features predict its presence.
Materials/Methods:
HYPCON-02 enrolled patients with resected HNSCC (oral cavity, oropharynx, larynx, hypopharynx) with positive margins and/or extranodal extension (ENE). Patients were randomized (1:2) to 60 Gy in 30 fractions or 50 Gy in 20 fractions with weekly cisplatin (40 mg/m²).
All patients underwent whole-body FDG PET 4–6 weeks postoperatively prior to CRT. Residual disease was defined as focal uptake greater than liver background within the operative bed with structural correlate. Patients with PET-defined gross residual disease were excluded from randomization. Associations with clinicopathologic features were assessed using Fisher’s exact test.
Results:
Eighty-three patients underwent pre-CRT PET. Oral cavity primaries comprised 89%, and 86% had stage IV disease. Pre-CRT PET identified unsuspected gross residual disease in 22 patients (26.5%), precluding randomization.
Among patients with PET-detected residual disease: T4 tumors (73%), ENE (86%), positive margins (32%), and tongue primaries (36%) were common. However, no conventional high-risk feature predicted residual disease (stage IV p=0.898; T4 p=0.254; ENE p=0.353; positive margins p=0.179; tongue primary p=0.164; age >50 p=0.818).
Conclusion:
More than one in four patients presumed eligible for adjuvant CRT harbored persistent macroscopic disease undetected by standard pathologic assessment. Importantly, traditional high-risk features failed to identify these patients.
These findings directly challenge the assumption that postoperative CRT universally treats microscopic disease and have immediate implications for radiation target delineation, de-intensification strategies, and postoperative trial design. Routine pre-CRT PET imaging may represent a critical refinement in the management paradigm of high-risk HNSCC.