Computed tomography (CT) is the most commonly used radiological response evaluation method in contemporary

oncology. However, it may not be optimally suitable for assessment of oncolytic virus treatments because

of paradoxical inflammatory tumor swellings, which result from virus treatments, particularly when viruses are

armed with immunostimulatory molecules. Here we investigated the prognostic utility of CT and [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oncolytic virus treatments. We also investigated

possible appearance of false-positive FDG signals in FDG-PET imaging of humans and hamsters treated with

oncolytic adenoviruses. First, immunocompetent Syrian hamsters were treated with intratumoral adenovirus

injections, tumor growth was followed up, and [18F]-FDG-uptake was quantitated with small animal PET/CT.

Second, we describe a retrospective patient series, essentially 17 individual case reports, of advanced cancer

patients treated with oncolytic adenoviruses in the context of an Advanced Therapy Access Program (ATAP)

who underwent radiological response evaluation with both contrast-enhanced CT and FDG-PET. Third, we

collected a retrospective case series of radiological response and survival data of 182 patients treated with

oncolytic adenoviruses in ATAP to evaluate the prognostic reliability of CT and FDG-PET. Overall, responses in

CT and FDG-PET correlated well with each other and were equally reliable as prognostic markers for long

survival after oncolytic adenovirus treatment. Interestingly, we observed that new FDG-avid lymph nodes

appearing in FDG-PET after virus treatments may represent inflammatory responses and therefore should not be

interpreted as treatment failure in the absence of other signs or verification of disease progression. We also

observed indications that FDG-PET might be more sensitive in detection of responses than tumor size.