Background Immunotherapy has demonstrated remarkable success in treating different cancers. Nonetheless, a large number of patients do not respond, many respond without immediate changes detectable with conventional imaging, and many have unusual immune-related adverse events that cannot be predicted in advance. In this exploratory study, we investigate how 3′-Deoxy-3’-¹⁸F-fluorothymidine (FLT) positron emission tomography (PET) measurements of tumor and immune cell proliferation might be utilized as biomarkers in immunotherapy. Methods Seventeen patients with metastatic castrate resistant prostate cancer were treated with combination pTVG-HP DNA vaccine and pembrolizumab. Patients underwent baseline and 12-week FLT PET/CT scans. FLT PET standardized uptake values (SUVs) were extracted from tumors, non-metastatic lymph nodes, spleen, bone marrow, pancreas, and thyroid to quantify cell proliferation in these tissues. Regional immune cell responses to pTVG-HP DNA vaccine were assessed by comparing FLT uptake changes in vaccine draining and non-draining lymph nodes. Cox proportional hazards regression was utilized to relate FLT uptake and other clinical markers (PSA and tumor size) to progression-free survival. Area under receiver operating characteristic (AUC) curves and concordance indices were used to assess the predictive capabilities of FLT uptake. Results Changes in FLT uptake in vaccine draining lymph nodes were significantly greater than changes in non-draining lymph nodes (P = 0.02), suggesting a regional immune response to vaccination. However, the changes in FLT uptake in lymph nodes were not significantly predictive of progression-free survival. Increases in tumor FLT uptake were significantly predictive of shorter progression-free survival (concordance index = 0.83, P < 0.01). Baseline FLT uptake in the thyroid was significantly predictive of whether or not a patient would subsequently experience a thyroid-related adverse event (AUC = 0.97, P < 0.01). Conclusions FLT PET uptake was significantly predictive of progression-free survival and the occurrence of adverse events relating to thyroid function. The results suggest FLT PET imaging has potential as a biomarker in immunotherapy, providing a marker of tumor and immune responses, and as a possible means of anticipating specific immune-related adverse events. Trial registration NCT02499835.

Background/Objectives: Determining how a patient with metastatic cancer is responding to therapy can be difficult for medical oncologists, especially with text-only radiology reports. In this investigation, we assess the clinical usefulness of a new algorithm-based analysis that provides spatial location and quantification for each detected lesion region of interest (ROI) and compare it to information included in radiology reports in the United States. Methods: Treatment response radiology reports for FDG PET/CT scans were retrospectively gathered from 228 patients with metastatic cancers. Each radiology report was assessed for the presence of both qualitative and quantitative information. A subset of patients (N = 103) was further analyzed using an algorithm-based service that provides the clinician with comprehensive quantitative information, including change over time, of all detected ROI with visualization of anatomical location. For each patient, three medical oncologists from different practices independently rated the usefulness of the additional analysis overall and in four subcategories. Results: In the 228 radiology reports, quantitative information of size and uptake was provided for at least one lesion at one time point in 78% (size) and 95% (uptake) of patients. This information was reported for both analyzed time points (current scan and previous comparator) in 52% (size) and 66% (uptake) of patients. Only 7% of reports quantified the total number of lesions, and none of the reports quantified changes in all lesions for patients with more than a few lesions. In the assessment of the augmentative algorithm-based analysis, the majority of oncologists rated it as overall useful for 98% of patients (101/103). Within specific categories of use, the majority of oncologists voted to use it for making decisions regarding systemic therapy in 97% of patients, for targeted therapy decisions in 72% of patients, for spatial location information in 96% of patients, and for patient education purposes in 93% of patients. Conclusions: For patients with metastatic cancer, the algorithm-based analysis of all ROI would allow oncologists to better understand treatment response and support their work to more precisely optimize the patient’s therapy.