Abstract

<h3>Purpose/Objective(s)</h3> De-escalation of therapy for anal squamous cell carcinoma is under investigation in multiple prospective randomized trials. Imaging metrics from (F-18) fluorodeoxyglucose positron emission tomography (PET) before and during chemoradiation may serve as a biomarker to tailor treatment and aid in appropriate patient and dose selection. <h3>Materials/Methods</h3> From June 2012 to July 2021, 56 patients with anal canal cancer were enrolled in two prospective studies (30 and 26 patients, respectively) of PET prior to and during CRT after receiving ∼30 Gy. PET metrics of the primary site were calculated for the pre-treatment and interim images, including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) based on 40% SUVmax (MTV40, TLG40) or SUV 2.5 (MTV2.5, TLG2.5) thresholds. Associations between absolute pre-treatment and interim PET metrics and freedom from local/regional recurrence (FFLR) were investigated using the Cox proportional hazards method. Local/regional recurrence was defined as primary or nodal (in-field) recurrence. No adjustment was made for multiple comparisons. <h3>Results</h3> Forty-four patients were eligible for analysis. Patients with non-squamous cell histology (adenocarcinoma, melanoma) (3 patients), recurrent anal cancer (1 patient), metastatic disease (1 patient), and incomplete studies due to treatment toxicity or patient choice (7 patients) were excluded. Median follow-up was 2.4 years. Clinical stage was T3 or T4 in 43% of patients, and 52% were node positive. Seven patients have expired and disease recurrence patterns following treatment included local/regional (5 patients) and distant disease (7 patients). On univariate analysis, age, T and N stage, duration of treatment, and HIV status did not significantly correlate with FFLR. TLG2.5 (1.05 [0.99-1.11]) was marginally associated with FFLR. No pretreatment metrics or other interim metrics were significantly associated with FFLR. Multivariate analysis was not conducted given the small number of events (N=5). <h3>Conclusion</h3> In this expanded pilot study, characteristics of PET acquired during treatment of anal canal cancer were not significantly associated with FFLR. Given the limited number of FFLR events, definitive conclusions about the utility of interim PET cannot be drawn. The correlation of various PET metrics with FFLR warrants further investigation to determine if interim PET as an imaging biomarker can be used to personalize treatment, potentially in the setting of dose de-escalation.

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