ABSTRACT
Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.
ABSTRACT
BACKGROUND: A hypothetical advantage of the da Vinci console is its ability to integrate multiple visual data sources. Current platforms for augmented reality surgery fuse pre-operative radiographic studies but are limited with their ability to update with intra-operative imaging. The aim of our study was to evaluate the feasibility of real-time radiographic image overlay with current technology. METHODS: S-video composite output from a fluoroscopic C-arm was superimposed onto the video output of the da Vinci device. Image superimposition disparity measurements were evaluated in a bench model. The feasibility of robotic dissection assisted by real-time cholangiogram and intravenous pyelogram was evaluated. RESULTS: Image alignment resulted in a radiographic blind spot and image disparity with severely limited application in an in vivo model. CONCLUSIONS: External collisions of the robotic device and visual disparity in multiple planes negate the current implementation of fluoroscopic overlay and will require more elegant methods of computer-assisted registration.
