FDG-PET/CT scan assessment of response 12 weeks post radical radiotherapy in oropharynx head and neck cancer: The impact of p16 status

Purpose: To evaluate the predictive value of FDG-PET/CT for detection of residual disease after radical radiotherapy for patients with squamous cell carcinoma (SCC) of the oropharynx, comparing p16 positive (+) versus p16 negative (-) disease.

Methods and materials: A retrospective analysis of patients with SCC of the oropharynx at our institution treated with radical radiotherapy between 2012 and 2016 was performed. The primary and lymph node metabolic responses were evaluated independently on the post-treatment FDG-PET/CT. The reference standard was pathology when available, subsequent post-treatment FDG-PET/CT results or clinical follow-up.

Results: Median follow-up time was 32 (30-34) months. 556 patients had p16+ disease and 92 had p16- disease. The median time of post-treatment FDG-PET/CT was 96 (45-744) days after radiotherapy completion: 68% had complete metabolic response (CMR) defined as mild non-focal or no uptake, 10% residual primary disease, 11% residual regional lymph node disease, 5% residual primary and regional disease, and 6% distant metastatic disease. The local positive predictive value (PPV) was 26% for p16+ versus 54% for p16- (p = 0.01) and the regional PPV was 31% for p16+ versus 58% for p16- (p = 0.01). The local negative predictive value (NPV) was 100% regardless of p16 status and the regional NPV was 100% for p16+ versus 99% for p16- (p = 0.33). For p16+ cases, regional specificity was 76.2% versus 91.1% (p = 0.0003), local PPV was 0 versus 30% (p = 0.06) and the regional PPV was 12% versus 35% (p = 0.06) for FDG-PET/CT scans performed at ≤12 weeks versus >12 weeks. Five-year overall survival for those with CMR was 87% versus 51% without CMR (p ≤ 0.001).

Conclusions: Metabolic response on post-treatment FDG-PET/CT has excellent NPV regardless of p16 status. The PPV is significantly lower in those with p16+ versus p16- disease, with a significantly reduced regional specificity and a trend towards inferior predictive value if performed ≤12 weeks. CMR predicts for a significantly improved overall survival.