Use of advanced PET-volume metrics predicts risk of local recurrence and overall survival in anal cancer

OBJECTIVE: Anal cancer is an uncommon malignancy with the primary treatment for localized disease being concurrent radiation and chemotherapy. Pre-treatment PET/CT is useful for target delineation, with minimal exploration of its use in prognostication. In the post-treatment setting there is growing evidence for advanced PET metrics in assessment of treatment response, and early identification of recurrence essential for successful salvage, however this data is limited to small series. METHODS: Patient with non-metastatic anal cancer from a single institution were retrospectively reviewed for receipt of pre- and post-treatment PET/CTs. PET data was co-registered with radiation therapy planning CT scans for precise longitudinal assessment of advanced PET metrics including SUV(max), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), for assessment with treatment outcomes. Treatment outcomes included local recurrence (LR), progression free survival (PFS), and overall survival (OS), as defined from the completed radiation therapy to the time of the event. Cox proportional hazard modeling with inverse probability weighting (IPW) using the propensity score based on age, BMI, T-stage, and radiation therapy dose were utilized for assessment of these metrics. RESULTS: From 2008 to 2017 there were 72 patients who had pre-treatment PET/CT, 61 (85%) had a single follow up PET/CT, and 35 (49%) had two follow up PET/CTs. The median clinical follow-up time was 25 months (IQR: 13–52) with a median imaging follow up time of 16 months (IQR: 7–29). On pre-treatment PET/CT higher MTV(2.5) and TLG were significantly associated with higher risk of local recurrence (HR 1.11, 95% CI: 1.06–1.16, p<0.001; and HR 1.12, 95% CI: 1.05–1.19, p<0.001), and worse PFS (HR 1.09, 95% CI: 1.04–1.13, p<0.001; and HR 1.09, 95% CI: 1.03–1.12, p = 0.003) and OS (HR 1.09, 95% CI: 1.04–1.16, p = 0.001; and HR 1.11, 95% CI: 1.04–1.20, p = 0.004). IPW-adjusted pre-treatment PET/CT showed higher MTV(2.5) (HR 1.09, 95% CI: 1.02–1.17, p = 0.012) and TLG (HR 1.10, 95% CI: 1.00–1.20, p = 0.048) were significantly associated with worse PFS, and post-treatment MTV(2.5) was borderline significant (HR 1.16, 95% CI: 1.00–1.35, p = 0.052). CONCLUSION: Advanced PET metrics, including higher MTV(2.5) and TLG, in the pre-treatment and post-treatment setting are significantly associated with elevated rates of local recurrence, and worse PFS and OS. This adds to the growing body of literature that PET/CT for patient with ASCC should be considered for prognostication, and additionally is a useful tool for consideration of early salvage or clinical trial of adjuvant therapies.