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Select patients with relapsed/refractory aggressive B cell lymphoma may benefit from bridging radiation (bRT) prior to anti-CD19-directed chimeric antigen receptor T cell therapy (CAR-T). Here, we examined patient and treatment factors associated with outcomes and patterns of failure after bRT and CAR-T. We retrospectively reviewed adults with diffuse large B-cell lymphoma (DLBCL) who received bRT prior to axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel between 11/2017-4/2023. Clinical/treatment characteristics, response, and toxicity were extracted. Survival was modeled using Kaplan-Meier or Cox regression models for events distributed over time, or binary logistic regression for disease response. Fisher's Exact Test or Mann-Whitney U methods were used. Of 51 patients, 25.5% had bulky disease and 64.7% had Stage III/IV disease at the time of RT. Comprehensive bRT alone to all disease sites was delivered to 51% of patients, and 29.4% were additionally bridged with systemic therapy. Median follow-up was 10.3 months (95% CI: 7.7-16.4). Overall response rate (ORR) was 82.4% at 30 days post-CAR-T infusion. Median overall survival (OS) was 22.1 months (6.6-not reached) and the median progression-free survival (PFS) was 7.4 months (5.5-30). OS/PFS were 80% (66-99)/78% (64-87) at 1-year, and 59% (44-71)/54% (40-67) at 2-years, respectively. Comprehensive RT to all sites of disease correlated with improved PFS and OS, 0.04. Additionally, ECOG ≥2 and Stage III/IV disease predicted poor OS ( 0.02). Disease bulk, IPI ≥3, and non-GCB histology were poor predictors for disease-specific survival (DSS), <0.05. The latter two, as well as bRT dose of ≤30 Gy predicted worse PFS ( <0.05). Among patients with advanced stage disease, comprehensive bRT to all sites of disease ( =10) was not associated with improved OS and PFS compared to focal bRT ( =23), >0.17. No difference was seen in bridging RT vs. chemoRT. Twenty-six patients developed relapse (50.9%), of which 46% was in-field. Risk of in-field relapse correlated with bulky disease (OR=7, 95% CI: 1.2-41, =0.03) and lack of response at 30 day post-CAR-T evaluation (OR=16.8, 95% CI: 1.6-176, =0.02), but not with bRT dose ( =0.27). bRT and CART is a good treatment strategy for select patients with aggressive B cell lymphoma. Comprehensive bRT including all sites of disease is associated with improved outcomes.

Background The incidence of anal squamous cell carcinoma has been increasing, particularly in people living with HIV (PLWH). There is concern that radiosensitizing drugs, such as protease inhibitors, commonly used in the management of HIV, may increase toxicities in patients undergoing chemoradiation. This study examines treatment outcomes and toxicities in PLWH managed with and without protease inhibitors who are receiving chemoradiation for anal cancer. Methods Patient demographic, HIV management, and cancer treatment information were extracted from multiple Veterans Affairs databases. Patients were also manually chart reviewed. Among PLWH undergoing chemoradiation for anal carcinoma, therapy outcomes and toxicities were compared between those treated with and without protease inhibitors at time of cancer treatment. Statistical analysis was performed using chi-square, Cox regression analysis, and logistic regression. Results A total of 219 PLWH taking anti-retroviral therapy undergoing chemoradiation for anal cancer were identified and included in the final analysis. The use of protease inhibitors was not associated with any survival outcome including colostomy-free survival, progression-free survival, or overall survival (all adjusted hazard ratio p -values> 0.05). Regarding toxicity, protease inhibitor use was not associated with an increased odds of hospitalizations or non-hematologic toxicities; however, protease inhibitor use was associated with increased hospitalizations for hematologic toxicities, including febrile neutropenia ( p  < 0.01). Conclusion The use of protease inhibitors during chemoradiation for anal carcinoma was not associated with any clinical outcome or increase in non-hematologic toxicity. Their use was associated with increased hospitalizations for hematologic toxicities. Further prospective research is needed to evaluate the safety and efficacy of protease inhibitors for patients undergoing chemoradiation.

ObjectivePelvic floor dysfunction is a common adverse effect of uterine cancer treatment. In this study we compared patient-reported outcomes regarding pelvic floor dysfunction among uterine cancer survivors after hysterectomy and bilateral salpingo-oophorectomy, surgery and brachytherapy, or surgery and external beam radiotherapy with or without brachytherapy versus women who had a hysterectomy for benign indications.MethodsWe used the validated 20-item Pelvic Floor Distress Inventory to assess lower urinary distress, colorectal distress, and pelvic organ prolapse dysfunction in each treatment group. Pelvic floor dysfunction-related quality of life in these domains was compared across treatment modalities using the Pelvic Floor Impact Questionnaire-7. Treatment type, body mass index, comorbidities, and number of vaginal births were obtained from medical records. A zero-inflated negative binomial regression model was used to assess the association of treatment regimens and covariates relative to the non-cancer cohort.ResultsA total of 309 surveys were analyzed. The median age of the patients at surgery was 58 years (range 20–87) and the median age at survey completion was 66 years (range 34–92). Most participants reported experiencing at least one symptom of pelvic floor dysfunction (76% by Pelvic Floor Distress Inventory-2). The type of treatment had no effect on overall pelvic floor dysfunction on multivariate analysis (all p>0.05). Worse urinary-related symptoms were associated with higher body mass index at surgery (OR 1.41), higher age at time of survey (OR 1.07), and higher numbers of vaginal births (OR 1.43) (all p<0.05).ConclusionsOverall, pelvic floor dysfunction did not significantly vary by treatment modality. Our findings suggest complex interactions among age, body mass index, and parity as to how uterine cancer treatment affects pelvic floor quality of life, which should be considered in the choice of treatment strategy and patient counseling.

Dedifferentiated liposarcoma (DDLPS) is one of the most common types of soft tissue sarcoma (STS) characterized by liposarcomatous differentiation and a predilection for the retroperitoneum. Despite the growing number of histology-specific immune checkpoint blockade (ICB) trials in STS, it is still difficult to identify the radiographic objective response rate (ORR) for DDLPS in the real world setting. This study aimed to evaluate the ORR and survival of patients with DDLPS treated with ICB at a single center. We conducted a retrospective study of 31 patients with pathologically confirmed DDLPS treated with ICB at MD Anderson Cancer Center between 2018 and 2023. Patient demographics, disease characteristics, treatment history, and response to ICB were analyzed. Immunohistochemical analysis was performed on tumor samples to assess immune-related markers. ORR by RECIST 1.1 was 3.2% (n=1/31). Among all patients (n=31), 6% achieved partial radiographic response, while 39% had stable disease, and 55% showed progressive disease. Median progression-free survival (PFS) was 3.5 (95%CI:1.9, 4.7) months, and overall survival (OS) after ICB initiation was 19.7 (95%CI: 8.8, not reached) months. Patients without prior systemic therapy demonstrated better OS (p=0.004). Immunohistochemistry revealed no relationship between pre- or post-ICB expression of CD8, CD20, CD21 and PDL-1 and response. While the response to ICB in DDLPS remains limited, specific immune markers may influence treatment outcomes. CD20/21 post-ICB appear more important for prognosis. Further research is warranted to identify predictive factors for ICB efficacy in DDLPS.

With 222,500 new cases estimated for 2017, prostate cancer makes up approximately 10% of all new cancer diagnoses in the United States and is the third most common cancer after breast and lung cancer. In 2013, the American Society of Radiation Oncology (ASTRO) policy model recognized that stereotactic body radiation therapy (SBRT) may be used as an alternative to standard treatment modalities, i.e. intensity modulated radiation therapy (IMRT), to treat prostate cancer. In this study, we report outcomes for a cohort of 30 patients with prostate cancer treated with SBRT at our institution. We also describe, in detail, the technical aspects of SBRT planning and delivery for these patients, specifically the use of MRI in determining treatment volumes and detecting gross lesions. After institutional review board (IRB) approval, a retrospective analysis was done of 30 males with the diagnosis of prostate cancer treated in the Department of Radiation Oncology at the Baylor College of Medicine between January 2011 and June 2016. All patients received image-guided SBRT. Treatment planning was performed using a non-contrast computed tomography (CT) scan as well as a contrast thin-slice open MRI with the patient in the treatment position. Patient comparisons were done using the Mann-Whitney U, Fishers Exact, and Kaplan-Meier tests. Thirty patients were treated between January 2011 and June 2016. Twenty-six had follow-up data available and were included in the analysis. Median follow-up was 32 months (range 2-72 months). Mean and median ages at diagnosis were both 68.5 years. A total of 64% of the patients had foci on magnetic resonance imaging (MRI) or a palpable nodule on an exam. The median prostate-specific antigen (PSA) at diagnosis was 7.35 ng/mL (range 2.8-13), and the median PSA nadir after treatment was 0.4 ng/mL (range 0.01-4.5). The biochemical disease-free recurrence rate per Phoenix definition was 96%, with only one patient experiencing a biochemical recurrence four years after treatment. The patient with a recurrence was T2c, high-intermediate risk with a Gleason score of 7(3+4). He had a focus visible on MRI. Overall survival was 96%, with the only patient death unrelated to his prostate cancer. There was no statistical significance associated with recurrence and nodule on MRI (p=0.318), T-stage (p=0.222), Gleason score (p=0.890), risk group (p=0.654), age (p=0.692), or race (p=0.509). There were no grade three or four acute or long-term toxicities. SBRT of the prostate is an effective method for treating prostate cancer. We saw excellent PSA control and minimal acute or long-term toxicities after a median of three years of follow-up.

The fission yeast clade—comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus—occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade.

The clover seed weevil, Tychius picirostris Fabricius, a serious pest of white clover, Trifolium repens L., grown for seed in western Oregon, causing feeding damage to flowers and developing seeds. Since 2017, white clover seed producers have anecdotally reported T. picirostris control failures using foliar pyrethroid insecticide applications. This mode of action (MoA) is an important chemical control option for T. picirostris management.To evaluate insecticide resistance selection to pyrethroids (bifenthrin) and other MoAs labeled for T. picirostris management (malathion and chlorantraniliprole), adult populations were collected from 8 commercial white clover grown for seed fields in the Willamette Valley, OR, in 2022 and 2023. Among collected Oregon populations, very high resistance ratios (RR50 = 178.00–725.67) were observed to technical grade bifenthrin and low to high resistance ratios (RR50 = 7.80–32.80) to malathion in surface contact assays compared to a susceptible Canadian field population. Moreover, >2.73 times the labeled rate of formulated product containing bifenthrin as the sole MoA was required to kill >50% of T. picirostris in topical assays. Synergistic assays with a mixed-function oxidase inhibitor, an esterase inhibitor, and a glutathione-S-transferase inhibitor revealed phase I and II detoxification enzymes are present in Oregon T. picirostris populations and confer metabolic resistance to bifenthrin.This is the first report of T. picirostris insecticide resistance selection to pyrethroid and organophosphate insecticides. Results will inform continued monitoring and insecticide resistance management strategies to slow the evolution of T. picirostris insecticide resistance selection in Oregon's white clover seed production.

Smoking rates among low-income individuals, including those eligible for Medicaid, have not shown the same decrease that is observed among high-income individuals. The rate of smoking among pregnant women enrolled in Medicaid is almost twice that among privately insured women, which leads to significant disparities in birth outcomes and a disproportionate cost burden placed on Medicaid. Several states have identified maternal smoking as a key target for improving birth outcomes and reducing health care expenditures; however, efficacious, cost-effective, and feasible cessation programs have been elusive. This study aims to examine the feasibility, acceptability, and effectiveness of a smartwatch-enabled, incentive-based smoking cessation program for Medicaid-eligible pregnant smokers. Pilot 1 included a randomized pilot study of smartwatch-enabled remote monitoring versus no remote monitoring for 12 weeks. Those in the intervention group also received the SmokeBeat program. Pilot 2 included a randomized pilot study of pay-to-wear versus pay-to-quit for 4 weeks. Those in a pay-to-wear program could earn daily incentives for wearing the smartwatch, whereas those in pay-to-quit program could earn daily incentives if they wore the smartwatch and abstained from smoking. Pilot 3, similar to pilot 2, had higher incentives and a duration of 3 weeks. For pilot 1 (N=27), self-reported cigarettes per week among the intervention group declined by 15.1 (SD 27) cigarettes over the study; a similar reduction was observed in the control group with a decrease of 17.2 (SD 19) cigarettes. For pilot 2 (N=8), self-reported cigarettes per week among the pay-to-wear group decreased by 43 cigarettes (SD 12.6); a similar reduction was seen in the pay-to-quit group, with an average of 31 (SD 45.6) fewer cigarettes smoked per week. For pilot 3 (N=4), one participant in the pay-to-quit group abstained from smoking for the full study duration and received full incentives. Decreases in smoking were observed in both the control and intervention groups during all pilots. The use of the SmokeBeat program did not significantly improve cessation. The SmokeBeat program, remote cotinine testing, and remote delivery of financial incentives were considered feasible and acceptable. Implementation challenges remain for providing evidence-based cessation incentives to low-income pregnant smokers. The feasibility and acceptability of the SmokeBeat program were moderately high. Moreover, the feasibility and acceptability of remote cotinine testing and the remotely delivered contingent financial incentives were successful. ClinicalTrials.gov NCT03209557; https://clinicaltrials.gov/ct2/show/NCT03209557.