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FLT PET/CT imaging of metastatic prostate cancer patients treated with pTVG-HP DNA vaccine and pembrolizumab.
- Source :
-
Journal for immunotherapy of cancer [J Immunother Cancer] 2019 Jan 30; Vol. 7 (1), pp. 23. Date of Electronic Publication: 2019 Jan 30. - Publication Year :
- 2019
-
Abstract
- 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'- <superscript>18</superscript> F-fluorothymidine (FLT) positron emission tomography (PET) measurements of tumor and immune cell proliferation might be utilized as biomarkers in immunotherapy.<br />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.<br />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).<br />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.<br />Trial Registration: NCT02499835 .
- Subjects :
- Dideoxynucleosides
Humans
Male
Positron Emission Tomography Computed Tomography
Antibodies, Monoclonal, Humanized therapeutic use
Antineoplastic Agents, Immunological therapeutic use
Prostatic Neoplasms, Castration-Resistant diagnostic imaging
Prostatic Neoplasms, Castration-Resistant therapy
Vaccines, DNA therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2051-1426
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal for immunotherapy of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 30700328
- Full Text :
- https://doi.org/10.1186/s40425-019-0516-1