IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab in patients with advanced cancer.

BACKGROUND: Doublet combination therapies targeting immune checkpoints have shown promising efficacy in patients with advanced solid tumors, but it is unknown if rational triplet combinations will be well tolerated and associated with improved antitumor activity. The objective of this trial was to determine the recommended phase 2 doses (RP2Ds) and to assess the safety and efficacy of the programmed cell death protein 1 (PD-1) inhibitor dostarlimab in combination with (1) the poly(ADP-ribose) polymerase inhibitor niraparib with or without vascular endothelial growth factor inhibitor bevacizumab or (2) carboplatin-paclitaxel chemotherapy with or without bevacizumab, in patients with advanced cancer. METHODS: IOLite is a multicenter, open-label, multi-arm clinical trial. Patients with advanced solid tumors were enrolled. Patients received dostarlimab in combination with niraparib with or without bevacizumab or in combination with carboplatin-paclitaxel with or without bevacizumab until disease progression, unacceptable toxicity, or withdrawal from the study. Prespecified endpoints in all parts were to evaluate the dose-limiting toxicities (DLTs), RP2Ds, pharmacokinetics (PKs), and preliminary efficacy for each combination. RESULTS: A total of 55 patients were enrolled; patients received dostarlimab and: (1) niraparib in part A (n=22); (2) carboplatin-paclitaxel in part B (n=14); (3) niraparib plus bevacizumab in part C (n=13); (4) carboplatin-paclitaxel plus bevacizumab in part D (n=6). The RP2Ds of all combinations were determined. All combinations were safe and tolerable, with no new safety signals observed. DLTs were reported in 2, 1, 2, and 0 patients, in parts A-D, respectively. Preliminary antitumor activity was observed, with confirmed Response Evaluation Criteria in Solid Tumors v1.1 complete/partial responses reported in 4 of 22 patients (18.2%), 6 of 14 patients (42.9%), 4 of 13 patients (30.8%), and 3 of 6 (50.0%) patients, in parts A-D, respectively. Disease control rates were 40.9%, 57.1%, 84.6%, and 83.3%, in parts A-D, respectively. Dostarlimab PK was unaffected by any combinations tested. Coadministration of bevacizumab showed no impact on niraparib PKs. The overall mean PD-1 receptor occupancy was 99.0%. CONCLUSIONS: Dostarlimab was well tolerated in both doublet and triplet regimens tested, with promising antitumor activity observed with all combinations. We observed higher disease control rates in the triplet regimens than in doublet regimens. TRIAL REGISTRATION NUMBER: NCT03307785.

Adult fingers visualized on neonatal intensive care unit chest radiographs: what you don't see.

PURPOSE: In a previous publication, it was revealed that a disturbingly high incidence of adult fingers were seen on pediatric intensive care unit radiographs, an example of inappropriate occupational exposure to diagnostic radiation. The present study examined adult fingers seen on neonatal intensive care unit (NICU) radiographs to assess the frequency of this occupational radiation exposure. During this study, we encountered an unexpected issue. The inappropriately exposed fingers appeared on the raw images but were sometimes cropped during technologist image processing before being sent to the picture archiving and communication system (PACS) for interpretation. Our audit describes the frequency of cropping adult fingers from images before display on PACS, with the intent of unmasking this source of occupational radiation exposure, of which quality assurance personnel may not be aware. METHODS: At the x-ray workstation, the raw NICU source x-ray images were analysed for the visibility of adult fingers and then were compared with the final processed images sent to PACS by the x-ray technologist. RESULTS: Of 230 radiographs audited, 30 (13%) contained fingers directly in the x-ray beam that remained visible on PACS, 22 (10%) contained fingers in the direct beam that were cropped before being sent to PACS for analysis, and 44 (19%) contained fingers in the coned area. CONCLUSIONS: A significant number of adult fingers are being exposed to radiation during the acquisition of NICU radiographs. Cropping NICU radiographs before sending them to PACS can conceal a significant source of occupational radiation exposure.

Reduction of adult fingers visualized on pediatric intensive care unit (PICU) chest radiographs after radiation technologist and PICU staff radiation safety education.

PURPOSE: A recent publication from our centre revealed a disturbing finding of a significant incidence of adult fingers seen on the pediatric intensive care unit (PICU) chest radiographs. This is inappropriate occupational exposure to diagnostic radiation. We hypothesized that the incidence of adult fingers on PICU chest radiographs would decline after radiation safety educational seminars were given to the medical radiation technologists and PICU staff. METHODS: The present study's objectives were addressed by using a pretest-posttest design. Two cross-sectional PICU chest radiograph samples, taken before and after the administration of radiation safety education for our medical radiation technologists and PICU staff, were compared by using a chi2 test. RESULTS: There was a 61.2% and 76.9% reduction in extraneous adult fingers, directly exposed to the x-ray beam and those seen in the coned regions of the film, respectively, on PICU chest radiographs (66.7% reduction overall). This reduction was statistically significant (chi2 = 20.613, P < .001). CONCLUSIONS: Limiting unnecessary occupational radiation exposure is a critical issue in radiology. There was a statistically and clinically significant association between radiation safety education and the decreased number of adult fingers seen on PICU chest radiographs. This study provides preliminary evidence in favour of the benefit of radiation safety seminars.