Purpose/Objective(s) We sought to identify swallowing muscle dose-response thresholds associated with chronic radiation-associated dysphagia (RAD) after IMRT for oropharyngeal cancer. Materials/Methods T1-4 N0-3 M0 oropharyngeal cancer patients who received definitive IMRT and systemic therapy were examined. Chronic RAD was coded as any of the following ≥ 12 months post-IMRT: videofluoroscopy/endoscopy detected aspiration or stricture, gastrostomy tube and/or aspiration pneumonia. DICOM-RT plan data were autosegmented using a custom region-of-interest (ROI) library and included inferior, middle and superior constrictors (IPC, MPC, and SPC), medial and lateral pterygoids (MPM, LPM), anterior and posterior digastrics (ADM, PDM), intrinsic tongue muscles (ITM), mylo/geniohyoid complex (MHM), genioglossus (GGM), ), masseter (MM), Buccinator (BM), palatoglossus (PGM), and cricopharyngeus (CPM), with ROI dose-volume histograms (DVHs) calculated. Recursive partitioning analysis (RPA) was used to identify dose-volume effects associated with chronic-RAD, for use in a multivariate (MV) model. Results Of 300 patients, 34 (11%) had chronic-RAD. RPA showed DVH-derived MHM V69 (i.e. the volume receiving ≥69Gy), GGM V35, ADM V60, MPC V49, and SPC V70 were associated with chronic-RAD. A model including age in addition to MHM V69 as continuous variables was optimal among tested MV models (AUC 0.835). Conclusion In addition to SPCs, dose to MHM should be monitored and constrained, especially in older patients (>62-years), when feasible.

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While patients with severe haemophilic arthropathy of the elbow are likely to make gains in terms of pain control and range of motion following TEA, there are insufficient data to routinely recommend its use. Complication and infection rates are concerning, and the lack of survival analysis data makes it difficult to quantify the benefit to the patient in light of the risks and resources involved in the procedure.

Checkpoint inhibitors block the ‘off’ signals that are engaged when T cells interact with antigen-presenting cells, such as dendritic cells (DCs). This increases T cell activation and enhances the anti-tumor response. Here we demonstrate the use of advanced flow cytometry to evaluate these immunotherapies in vitro by co-culturing immune cells from two donors in an MLR assay. Assays were set up as either one-way or two-way MLR co-cultures. One-way assays combined isolated DCs from one donor with CD4+ T cells from another. Two-way assays mixed PBMCs from two donors. Cells and checkpoint inhibitors were plated in 96 or 384-well formats for 3–6 days. Samples taken during the time course were analyzed for cell subsets and cytokine concentrations using the iQue® Advanced Flow Cytometry Platform. Expression of activation marker CD25 on T cells was 3-fold greater after 6 days in co-culture with DCs (62 ± 2 %) compared to T cells in monoculture (22 ± 9 %). The addition of an anti-PD1 checkpoint inhibitor induced a further, concentration dependent increase in CD25 expression. This was accompanied by increased production of cytokines indicative of activation and inflammation, such as TNFα and CCL2. Throughout the study, there were large differences in sensitivity to drug response between donor pairs. For example, IFNγ release increased 13.5-fold upon addition of anti-CTLA4 (17 ng/mL) with one donor pair, compared to only 1.3-fold with another. This highlights the need to characterize drug activity using multiple immune cell donor pairs. These data exemplify the use of advanced flow cytometry to generate pharmacological data for checkpoint inhibitor activity on T cells in MLR, with the potential to profile libraries of novel therapeutics in minimal time.

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ImportanceRetinal vein occlusion is the second most common retinal vascular disease. Bevacizumab was demonstrated in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) to be noninferior to aflibercept with respect to visual acuity in study participants with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) following 6 months of therapy. In this study, the cost-utility of bevacizumab vs aflibercept for treatment of CRVO is evaluated.ObjectiveTo investigate the relative cost-effectiveness of bevacizumab vs aflibercept for treatment of macular edema associated with CRVO or HRVO.Design, Setting, and ParticipantsThis economic evaluation study used a microsimulation cohort of patients with clinical and demographic characteristics similar to those of SCORE2 participants and a Markov process. Parameters were estimated and validated using a split-sample approach of the SCORE2 population. The simulated cohort included 5000 patients who were evaluated 100 times, each with a different set of characteristics randomly selected based on the SCORE2 trial. SCORE2 data were collected from September 2014 October 2019, and data were analyzed from October 2019 to July 2021.InterventionsBevacizumab (followed by aflibercept among patients with a protocol-defined poor or marginal response to bevacizumab at month 6) vs aflibercept (followed by a dexamethasone implant among patients with a protocol-defined poor or marginal response to aflibercept at month 6).Main Outcomes and MeasuresIncremental cost-utility ratio.ResultsThe simulation demonstrated that patients treated with aflibercept will have an expected cost $18 127 greater than those treated with bevacizumab in the year following initiation. When coupled with the lack of clinical superiority over bevacizumab (ie, patients treated with bevacizumab had a gain over aflibercept in visual acuity letter score of 4 in the treated eye and 2 in the fellow eye), these results demonstrate that first-line treatment with bevacizumab dominated aflibercept in the simulated cohort of SCORE2 participants. At current price levels, aflibercept would be considered the preferred cost-effective option only if treatment restored the patient to nearly perfect health.Conclusions and RelevanceWhile there will be some patients with CRVO-associated or HRVO-associated macular edema who will benefit from first-line treatment with aflibercept rather than bevacizumab, given the minimal differences in visual acuity outcomes and large cost differences for bevacizumab vs aflibercept, first-line treatment with bevacizumab is cost-effective for this condition.

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