Citations

Summary Outcomes for high‐risk paediatric classic Hodgkin lymphoma (cHL) improved with the addition of brentuximab vedotin (Bv) to doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (AVEPC) chemotherapy. We evaluated the prognostic implications of distant extra‐nodal sites contributing to stage IV disease. On AHOD1331 (NCT02166463), patients aged 2–21 years with high‐risk cHL (stage IIB with bulk/IIIB/IVA/IVB) were randomized to 5 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE‐PC) versus Bv‐AVEPC. Patients with stage IV disease, determined by protocol‐defined and centrally reviewed Positron Emission Tomography ‐ Computed Tomography (PET‐CT), were identified. Baseline characteristics and progression‐free survival (PFS) were compared by pattern of stage IV involvement (lung, bone, bone marrow, multiple sites and others). A total of 340 patients (median age 15 years) with stage IV disease were included. Of these patients, 173 (51%) received ABVE‐PC and 167 (49%) Bv‐AVEPC. PFS was highest with lung‐only involvement (4‐year PFS 88.6%) and lowest with bone marrow‐only involvement (4‐year PFS 71.9%). Compared to ABVE‐PC, Bv‐AVEPC improved PFS among all stage IV patients (hazard ratio [HR] 0.53, 90% confidence interval (CI) 0.33–0.85) and in the lung‐only and bone‐only subgroups. However, no PFS benefit was observed in those with bone marrow‐only involvement. Among paediatric patients with stage IV cHL, Bv‐AVEPC improved PFS across most patterns of stage IV disease, except in those with bone marrow involvement. These results will guide efforts to improve outcomes among children with stage IV cHL.

PURPOSE Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). METHODS Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. RESULTS Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub ( P < .05 for all). CONCLUSION White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.

Importance There is no consensus on staging and surveillance imaging for cutaneous squamous cell carcinoma (CSCC). Although imaging has been shown to affect management, broad recommendations from the National Comprehensive Cancer Network have led to variability in clinical practice. Objective To develop multidisciplinary consensus recommendations on the use of staging and surveillance imaging of localized CSCC. Evidence Review A multidisciplinary expert panel across academic and clinical practice settings convened a Delphi consensus, with 3 iterative survey rounds from January to June 2025. Data were analyzed from February 2025 to January 2026. Eligibility defined by at least 1 to 2 CSCC publications during the previous 5 years, involvement in a relevant clinical trial, experience treating at least 3 patients monthly with CSCC, and/or 5 years or longer of clinical practice. Fifty-four experts were invited and 45 (83%) completed all 3 rounds and were included in the final analysis. Structured Delphi surveys evaluated clinical scenarios, imaging modalities, and surveillance strategies for CSCC. Consensus and near-consensus recommendations were generated, defined as 80% or greater and 70% to 79% agreement, respectively. Findings The 45 participants (21 female individuals [47%] and 24 male individuals [53%]; 14 Asian individuals [31%], 1 multiracial individual [2%], and 30 White individuals [67%]) consisted of dermatology (15 [33%]), medical oncology (7 [16%]), radiation oncology (9 [20%]), radiology (9 [20%]), surgery (3 [7%]), and otolaryngology specialists (2 [4%]). The Delphi panel recommended staging and surveillance for CSCCs with at least a 15% risk of metastasis. Consensus or near consensus was reached to recommend staging and surveillance imaging for tumors with a concern for metastasis, bone invasion, invasion beyond subcutaneous fat, large-caliber nerve invasion, or a diameter of 4 cm or larger or the combination of tumors with poorly differentiated histology and any of the following: diameter of 2 cm or larger, lymphovascular invasion and subcutaneous fat invasion, or lymphovascular invasion and small-caliber perineural invasion. Computed tomography imaging was the preferred modality for nodal staging (38 [84%]) and surveillance (35 [78%]). For surveillance duration, consensus was reached to provide imaging for at least 2 years, and near consensus was reached for at least 3 years. Conclusions and Relevance This study provides an expert consensus–based framework to standardize imaging in localized CSCC that may inform future guidelines.

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.

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

ABSTRACT Clinical pharmacists are increasingly recognized as vital contributors to acute stroke care, yet their role remains inconsistently defined and underutilized across health care systems. This consensus statement explores the expanding presence of clinical pharmacists within interdisciplinary stroke teams, particularly in the management of both acute ischemic stroke ( AIS ) and hemorrhagic stroke. This consensus statement panel was composed of clinical pharmacists, emergency medicine physicians, and a vascular neurologist. The Grading of Recommendations, Assessment, Development, and Evaluation ( GRADE ) approach was used to assess the level of certainty and strength of recommendations. We focused on two questions regarding the clinical pharmacist's role in caring for adult patients presenting to the emergency department ( ED ) with AIS or hemorrhagic stroke. Despite the very low level of evidence, a consensus was reached for the following recommendations: (1) clinical pharmacist involvement in AIS care for adult patients presenting to the ED and (2) clinical pharmacist involvement in hemorrhagic stroke care for adult patients presenting to the ED . Based on the available literature, we believe optimizing the clinical pharmacist role is a critical factor in improving time‐sensitive treatment and equity in care delivery.

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 Immune checkpoint inhibitor-based combinations represent the standard of care for advanced renal cell carcinoma. The OMNIVORE trial investigated a response-adaptive strategy, including treatment discontinuation in early nivolumab responders (Arm A) and salvage ipilimumab addition in non-responders (Arm B). Here we report outcomes with extended follow-up. Methods OMNIVORE was a phase II response-adaptive trial in which patients received induction nivolumab monotherapy. Patients achieving a confirmed complete or partial response discontinued nivolumab and entered observation (Arm A), while patients with stable disease or progressive disease received two doses of ipilimumab added to ongoing nivolumab (Arm B). This analysis characterizes long-term overall survival across the full study cohort and durability of response among patients who discontinued nivolumab following an early objective response. Results Of 83 patients who initiated treatment, 12 (14%) were allocated to Arm A and 57 (69%) to Arm B, with a median follow-up among living patients of 59.4 months (range 29.1–85.4 months) in Arm A and 31.4 months (range 4.6–62.6 months) in Arm B. The 3-year overall survival rate from nivolumab initiation was 64% (95% CI 51% to 74%) in the overall cohort, 83% (95% CI 48% to 96%) in Arm A, and 63% (95% CI 47% to 76%) in Arm B. Of the 12 Arm A patients, 6 (50%) remained off nivolumab at 1 year following treatment discontinuation, of whom 5 maintained responses beyond 43 months off therapy, with all remaining alive at last known follow-up, with overall survival ranging from 48.8 to 85.4 months from nivolumab initiation. Of the six patients who resumed treatment, only one achieved a durable complete response remaining on treatment at 83.2 months from nivolumab initiation. All 57 Arm B patients discontinued treatment with a median treatment duration of 3.7 months (range 1–24.8 months) and a median progression-free survival from nivolumab plus ipilimumab initiation of 4.6 months (95% CI 2.7 to 6.5 months). Conclusions With extended follow-up, a meaningful subset of patients achieving an early objective response to nivolumab maintained prolonged treatment-free survival following a short course of treatment. Salvage ipilimumab in nivolumab non-responders demonstrated limited benefit, reinforcing that upfront concurrent dual checkpoint blockade remains the preferred approach. Trial registration number NCT03203473 .

Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies ranging from relatively indolent well-differentiated neuroendocrine tumors (NETs) to more aggressive poorly differentiated neuroendocrine carcinomas (NECs). The advent of somatostatin receptor (SSTR)–targeting therapies, particularly radioligand therapy (RLT), has transformed the therapeutic landscape of NETs. Ongoing efforts are aimed at maximizing the therapeutic benefit of RLT and include retreatment and combination strategies as well as novel α-emitter–based radiopharmaceuticals. The increasing use of molecular profiling has led to the identification of recurrent canonical alterations in pancreatic NETs, including in MEN1 , ATRX / DAXX , PI3K/Akt/mTOR, and angiogenic signaling pathways, facilitating the development of effective targeted therapies. However, despite the addition of newer targeted therapies to the therapeutic armamentarium, resistance remains inevitable and highlights the need for improved predictive markers to inform therapy sequencing and novel biomarker-selected therapies. In addition, the development of novel therapeutic strategies including SSTR antagonists, nonpeptide drug conjugates, and novel radiopharmaceutical constructs highlights the potential of biomarker-informed therapies in this space. By contrast, treatment options for NECs remain limited, with modest therapeutic benefit of platinum-based chemotherapy. The identification of delta-like ligand 3 (DLL3) as a therapeutic target in high-grade NENs has led to the development of novel targeted therapies such as T-cell engagers, which have demonstrated promising activity in early phase clinical trials. In addition, other DLL3-targeting agents such as antibody-drug conjugates, trispecific engagers, and cellular therapies remain under investigation. Collectively, these advances underscore the potential of biomarker-informed treatment approaches to personalize treatment decisions and improve long-term outcomes across the NEN spectrum.