Background: Indirect evidence suggests that optimal vitamin D status is achieved with a serum 25-hydroxyvitamin D [25(OH)D] concentration >75 nmol/L. Objective: We aimed to determine the intake of vitamin D₃ needed to raise serum 25(OH)D to >75 nmol/L. Design: The design was a 6-mo, prospective, randomized, double-blinded, double-dummy, placebo-controlled study of vitamin D₃ supplementation. Serum 25(OH)D was measured by radioimmunoassay. Vitamin D₃ intake was adjusted every 2 mo by use of an algorithm based on serum 25(OH)D concentration. Results: A total of 138 subjects entered the study. After 2 dose adjustments, almost all active subjects attained concentrations of 25(OH)D >75 nmol/L, and no subjects exceeded 220 nmol/L. The mean (±SD) slope at 9 wk [defined as 25(OH)D change/baseline dose] was 0.66 ± 0.35 (nmol/L)/(μg/d) and did not differ statistically between blacks and whites. The mean daily dose was 86 μg (3440 IU). The use of computer simulations to obtain the most participants within the range of 75–220 nmol/L predicted an optimal daily dose of 115 μg/d (4600 IU). No hypercalcemia or hypercalciuria was observed. Conclusions: Determination of the intake required to attain serum 25(OH)D concentrations >75 nmol/L must consider the wide variability in the dose-response curve and basal 25(OH)D concentrations. Projection of the dose-response curves observed in this convenience sample onto the population of the third National Health and Nutrition Examination Survey suggests a dose of 95 μg/d (3800 IU) for those above a 25(OH)D threshold of 55 nmol/L and a dose of 125 μg/d (5000 IU) for those below that threshold.

Purpose: Entrectinib potently inhibits tropomyosin receptor kinases (TRKAs)/B/C and ROS1, and previously induced deep [objective response rate (ORR) 57.4%] and durable [median duration of response (DoR) 10.4 months] responses in adults with NTRK fusion-positive solid tumors from three phase I/II trials. This article expands prior reports with additional patients and longer follow-up. Patients and Methods: Patients with locally advanced/metastatic NTRK fusion-positive solid tumors and ≥12 months' follow-up were included. Primary endpoints were ORR and DoR by blinded independent central review (BICR); secondary endpoints included progression-free survival (PFS), intracranial efficacy, and safety. The safety-evaluable populations included all patients who had received ≥1 entrectinib dose. Results: At clinical cut-off (August 31, 2020), the efficacy-evaluable population comprised 121 adults with 14 tumor types and ≥30 histologies. Median follow-up was 25.8 months; 61.2% of patients had a complete (n = 19) or partial response (n = 55). Median DoR was 20.0 months [95% confidence interval (CI), 13.0–38.2]; median PFS was 13.8 months (95% CI, 10.1–19.9). In 11 patients with BICR-assessed measurable central nervous system (CNS) disease, intracranial ORR was 63.6% (95% CI, 30.8–89.1) and median intracranial DoR was 22.1 (95% CI, 7.4–not estimable) months. The safety profile of entrectinib in adults and pediatric patients was aligned with previous reports. Most treatment-related adverse events (TRAEs) were grade 1/2 and manageable/reversible with dose modifications. TRAE-related discontinuations occurred in 8.3% of patients. Conclusions: With additional clinical experience, entrectinib continues to demonstrate durable systemic and intracranial responses and can address the unmet need of a CNS-active treatment in patients with NTRK fusion-positive solid tumors.

Vesicular stomatitis virus expressing interferon- is oncolytic and promotes antitumor immune responses in a syngeneic murine model of non-small cell lung cancer

Background Checkpoint inhibitors are a class of agents that employ host’s adaptive immune defenses in fighting cancer. With many new indications and several ongoing clinical trials in a variety of malignancies, the usage of these agents is set to increase significantly. One of the key challenges patients and physicians face while using these drugs is with the appropriate assessment of response to therapy. Case presentation We are reporting two patients with lung cancer who were treated with nivolumab and experienced rapidly accumulating recurrent pleural effusions requiring multiple thoracenteses (6 and 4 times each for patient 1 and 2 respectively) with in the first few weeks of initiation of therapy and also developed pericardial effusion with cardiac tamponade requiring pericardiocentesis. Both patients had prior history of malignant spread to pleural and pericardial space in their disease course. Therapy was continued in the first patient with spontaneous resolution of effusions after 8 weeks and the disease showed near complete response to treatment on imaging at 16 weeks. Second patient declined to continue further treatment with nivolumab after 3 cycles due to recurrent effusions and cardiac tamponade, although there was some evidence of clinical response at discontinuation. Conclusions Patients with history of malignant involvement of visceral spaces should be monitored closely for rapidly accumulating effusions and particularly for cardiac tamponade, after initiation of therapy with nivolumab. This presentation could represent pseudoprogression, and continuation of therapy with close monitoring is prudent as long as effusions are manageable and there is no definitive evidence of progression elsewhere.