Citations

ABSTRACT Management of prostate cancer has improved over the past two decades, driven by innovations in detection of metastatic disease, biomarker characterization, and treatment. This review summarizes the latest progress in managing advanced states of this disease, spanning high risk biochemical recurrence, metastatic hormone sensitive prostate cancer (mHSPC), and metastatic castration resistant prostate cancer (mCRPC). Improved outcomes for patients have been seen with earlier use of androgen receptor pathway inhibitors in the setting of high risk biochemical recurrence and mHSPC. Meanwhile, individuals with mCRPC now represent a more diverse population, differentiated by both their previous treatments and other biological features. Advanced imaging and genomic biomarkers improve patient selection and permit more personalized therapy. Landmark clinical trials and meta-analyses have established and/or refined the role of chemotherapy, poly-ADP ribose polymerase (PARP) inhibitors, and 177 Lu-PSMA-617 in this disease space. Finally, as patients with prostate cancer are living longer, the review focuses on understanding and managing potential adverse events, including cardiac and hematologic toxicity and bone health.

ABSTRACT Airway perforation is a potentially lethal complication from tracheal or mediastinal malignancies that require complex management. Advanced thyroid cancer is known to have high morbidity, and patients with tracheal metastatic lesions are vulnerable to injury. Therapeutic management typically comprises a combination of surgical and nonoperative treatment modalities, whose adverse effects can lead to significant airway injury. We present the case of a 67‐year‐old man with papillary thyroid carcinoma who developed a tracheocutaneous fistula following proton beam therapy and chemotherapy for metastatic disease. Airway repair and recanalization were successfully achieved through a combined surgical and bronchoscopic approach.

PURPOSE Social determinants of health (SDOH) shape cancer treatment access, adherence, and outcomes, yet their collection and use within National Clinical Trials Network (NCTN) studies remain poorly defined. This study examined how demographic and SDOH-related variables were historically collected and published to identify gaps that constrain the study of social context within NCTN trials. METHODS Participant-level data from completed phase III trials for gastrointestinal (GI) cancers conducted by the Alliance for Clinical Trials in Oncology (Alliance) or its legacy groups from 1999 to 2018 were pooled. Thirteen measures were assessed: four demographic and nine SDOH-related. The proportion of individual participants with data collected for each measure was evaluated. Data utilization was evaluated for all primary articles and via targeted review of related publications using the number either reporting subgroups or publishing analyses for each measure. RESULTS A total of 12,701 participants across 11 trials were included. All trials collected demographic measures (<2% of patients missing), insurance status (1% missing), and ZIP code (3% missing). Education level was collected in two trials (28% missing) with marital and employment status collected in one trial (41% missing for both). No trials collected data on other SDOH-related measures. Education level was the only SDOH-related measure reported in primary articles, and none reported analysis of SDOH-related measures. Of the 149 related publications, <2% reported or analyzed any SDOH-related measure. CONCLUSION Across Alliance and NCTN legacy group phase III trials for GI cancers, demographic variables have been consistently collected and frequently reported or analyzed, whereas SDOH-related measures are inconsistently collected and rarely published in the literature. These findings demonstrate a historical absence of routine SDOH data capture and utilization within NCTN trials.

Importance Risk-reducing salpingo-oophorectomy (RRSO) is an effective option to prevent ovarian cancer in high-risk individuals, but adverse effects from premature menopause are a barrier to uptake. Interval salpingectomy with delayed oophorectomy (ISDO) may be an effective alternative. Objective To evaluate the association of ISDO vs RRSO and sexual function and menopausal symptoms. Design, Setting, and Participants This prospective, multicenter, nonrandomized (patient preference) clinical trial was performed among Women Choosing Surgical Prevention participants with a pathogenic or likely pathogenic germline variant conferring an increased risk for ovarian cancer. Patients from 9 US centers were enrolled from June 2, 2016, to October 28, 2020; chose ISDO or RRSO; and were followed up for 24 months. The analysis was performed on November 13, 2024. Interventions Participant-selected RRSO or ISDO. Main Outcomes and Measures Changes in sexual function and menopausal symptoms from baseline to 6, 12, and 24 months. Inverse probability weighting was applied to achieve covariate balance across groups. Results The analytic sample included 334 female participants (mean [95% CI] age at consent, 39.2 [38.7-.9.7] years) who underwent RRSO (n = 165) or ISDO (n = 169) and completed 6-month questionnaires. Significantly more participants experienced clinically meaningful worsening of sexual function at 6 months compared with baseline after RRSO vs ISDO (33.1% [39 of 118] vs 16.8% [17 of 101], respectively; odds ratio, 2.00 [95% CI, 1.20-3.35]) and at 12 months (39.2% [38 of 97] vs 18.3% [17 of 93], respectively; odds ratio, 1.69 [95% CI, 1.09-2.63]). This finding was no longer significant at 24 months. When restricted to the RRSO group who took hormone replacement therapy, there was no significant worsening of total sexual function scores or menopausal symptoms compared with baseline. No interval ovarian cancers were reported. Conclusions and Relevance This nonrandomized clinical trial comparing RRSO with ISDO found that ISDO was less likely to impair sexual function, which addresses an important barrier to surgical prevention in high-risk patients in premenopause. After RRSO, use of hormone replacement therapy mitigated menopausal symptoms and prevented decline in sexual function. More information is needed about the safety of ISDO. Trial Registration ClinicalTrials.gov Identifier: NCT02760849

Patients with plasma cell leukemia (PCL) are generally excluded from pivotal T-cell redirecting bispecific antibody (BsAb) trials. We evaluated real-world outcomes in a multicenter retrospective study of 122 patients with primary or secondary PCL across 15 academic centers, categorized as 'active' (≥5% circulating plasma cells within 30 days of BsAb initiation) or 'historical'. In a heavily pretreated population, patients received teclistamab (37%), elranatamab (11%), talquetamab as a line of therapy (Tal LOT, 42%), or talquetamab as bridging therapy to CAR-T (Tal Bridge, 11%). Cytokine release syndrome (CRS) was grade 1-2 in 56% and grade 3-4 in 4%, whereas neurotoxicity was grade 1-2 in 16% and grade 3-4 in 5%. Among 110 evaluable patients, the overall response rate (ORR) was 55%, including 61% with Tal LOT, 58% with Tal Bridge, 46% with elranatamab, and 33% with teclistamab. With a median follow-up of 8.3 months, talquetamab demonstrated superior survival. Tal LOT showed a median progression-free survival (mPFS) of 5.5 months and a median overall survival (mOS) of 11.5 months, and both were unreached in the Tal Bridge cohort. In contrast, teclistamab and elranatamab showed a mPFS of 1.2 and 1.6 months and mOS of 8.1 and 3.6 months, respectively (P=0.007, P=0.023). In active PCL, Tal LOT achieved mPFS/mOS of 6.9/12.2 months versus 0.7/1.4 months with teclistamab and 1.0/3.1 months with elranatamab, respectively (P&lt;0.001, P=0.002). Multivariable analysis associated active PCL with worse survival and Tal LOT with improved outcomes. BsAbs were safe in PCL, with talquetamab showing superior outcomes compared with BCMA-directed BsAbs.

Abstract Improved understanding of how chimeric antigen receptor (CAR) and endogenous T‐cell phenotypes associate with progression‐free survival (PFS) is needed to individualize and improve immunotherapy outcomes in multiple myeloma (MM). We characterized and investigated the prognostic value of immune dynamics defined with multidimensional and computational flow cytometry in 258 bone marrow aspirates from 107 MM patients treated with idecabtagene vicleucel in the KarMMa trial. At screening, there was an association between longer PFS and increased percentages of PD1 + cytotoxic T cells and ICOS − TIGIT + Tregs. At Month 1 after infusion, the presence of >1% CAR‐T cells, a CD4/CD8 CAR‐T‐cell ratio >0.09, and greater abundance of non‐activated non‐cytolytic CAR‐T cells identified patients with longer PFS. Notably, 47 of the 115 endogenous T‐cell clusters were prognostic at the latest assessment performed after CAR‐T infusion. Lower percentages of ICOS + TIGIT − Tregs showed the strongest association with longer PFS. Altogether, this large dataset of dynamic immune profiling throughout treatment with anti‐B‐cell maturation antigen (anti‐BCMA) CAR‐T cells uncovered that the T‐cell composition prior to apheresis as well as CAR‐T and endogenous T‐cell phenotypes after infusion associates with PFS. These findings have potential for translation into routine laboratory practice for improved understanding of response and resistance to CAR‐T cells in relapsed/refractory MM.

Background: Nerve transfers have been heralded as a “quantum leap” in peripheral nerve surgery, fundamentally altering the reconstructive paradigm over the past 2 decades. This study analyzed national trends in adult traumatic brachial plexus injury (BPI) management, tracking specialty-specific adoption of nerve transfers and comparing 30-day postoperative outcomes with traditional reconstruction. Methods: Data were extracted from the National Surgical Quality Improvement Program (2006 to 2022). Adult patients (18 years or older) with a primary BPI diagnosis, who underwent nerve reconstruction, were included. Cases were categorized by the presence of a nerve transfer using CPT code 64905. Analyses included descriptive statistics, standardized mean differences, and multivariable logistic regression. Results: Among 544 BPI patients, 80 underwent reconstruction involving a nerve transfer. Plastic surgeons performed 60% of nerve transfers despite accounting for only 33.5% of all BPI reconstructions. Neurosurgeons had the lowest overall nerve transfer utilization but increased to a rate matching orthopedic surgeons in the final 4 years. Nerve transfers were associated with lower 30-day complication rates than traditional reconstruction (2.5% vs. 11%, P =0.034), despite being performed on patients with higher preoperative morbidity risk. In multivariable analysis, orthopedic and neurosurgeons remained significantly less likely than plastic surgeons to perform nerve transfers (OR: 0.26, P <0.001; OR: 0.18, P <0.001, respectively). Conclusion: Nerve transfer use in BPI reconstruction has increased steadily, with a recent increase among neurosurgeons. Despite being used in higher-risk patients, nerve transfers were associated with significantly lower short-term complication rates. These findings support continued adoption of nerve transfers and highlight their favorable safety profile.