• This study quantifies the inter-observer variability of manual delineation of lesions and organ contours in CT. • The variability of manual delineations between two observers can be significant. Two and even three observers capture only a fraction of the full range of inter-observer variability observed in common practice. • Inter-observer manual delineation variability is necessary to establish a reference standard for radiologist training and evaluation and for the evaluation of automatic segmentation algorithms.

Melanoma survival increased with targeted-and immunotherapy agents, yet most patients ultimately progress and require salvage therapy. In our experience, some progressive disease patients on immune-checkpoint inhibitors (ICIs) demonstrate deep and sustained responses to chemotherapy. We hypothesized that ICIs improve the response to subsequent chemotherapy in metastatic melanoma. We conducted a retrospective study to compare the efficacy of chemotherapy given with prior immunotherapy, to its efficacy given without it. We measured progression free survival (PFS), overall survival, and response rate. Immune-monitoring was performed on sequential peripheral blood mononuclear cell samples taken from a chemotherapy-responsive patient. The chemotherapy post-immunotherapy group (CpI) included 11 patients, the chemotherapy without prior immunotherapy (CNPI) group included 24 patients. Median PFS was 5.2 months in the CpI vs. 2.5 months in the CNPI groups; HR 0.37 [95% Confidence interval (CI) 0.144-0.983], P = 0.046. Immune-monitoring showed an increased proportion of CD8 + cells, with elevated PD-1 and CD69 expression, while on chemotherapy, as compared with all-time points on ICIs, suggesting immune-activation. Immunotherapy potentiates the effect of chemotherapy in metastatic melanoma possibly through activation of CD8 + T cells.

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