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.
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.
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 .