[¹⁸F]-Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography in Response Evaluation of Oncolytic Adenovirus Treatments of Patients with Advanced Cancer

Abstract

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 [(18)F]-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 [(18)F]-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.

T-cell Subsets in Peripheral Blood and Tumors of Patients Treated With Oncolytic Adenoviruses

“…This could reflect the problem posed by inflammatory swelling in using tumor size as a surrogate, a phenomenon likely to cause false negatives in assessment of efficacy by imaging 38 . Alternatively or in addition, this finding is compatible with a disconnect between antitumor T-cells and treatment responses, as discussed above, because just looking at the blood omits the effects of the tumor microenvironment.…”

Personalized Therapy of Cancer

“…In a comparative study of patients treated by viral oncolysis, FDG-PET was more sensitive in detection of responses than tumor size determined by CT (Koski et al 2013 ).…”

Serum HMGB1 is a predictive and prognostic biomarker for oncolytic immunotherapy

“…In case of PET-CT, the same percentages were used, but evaluation was based on change in SUVmax sum values, a modification of the PET Response Criteria in Solid Tumors, as previously described. 41 Oncolytic adenoviruses Oncolytic adenoviruses given to 202 patients as their first virus treatment have been previously published. 24,26,27,29,30,38,[42][43][44] To briefly characterize, ICOVIR-7 and Ad5-D24-RGD-GMCSF are serotype 5 adenoviruses with a capsid modification of the RGD motif in fiber region.…”

“…Abbreviations: Panc, pancreatic cancer; Bil, biliary cancer; HCC, hepatocellular carcinoma; CRC, colorectal cancer; GMCSF, granulocyte macrophage-colony stimulating factor; CD40L, CD40-ligand. 24,26,27,29,30,37,38,[41][42][43][44]50 e989771-6…”