Citations

The treatment landscape of invasive early-stage and metastatic breast cancer is evolving constantly. These NCCN Guidelines Insights focus on recent updates included in the most recent version (version 5.2025) of the NCCN Guidelines for Breast Cancer specific to workup, locoregional therapy, surveillance, and systemic neoadjuvant/adjuvant therapy recommendations for invasive, nonmetastatic breast cancer.

Background Outcome selection in regional anesthesia and acute pain research is inconsistent, often lacking patient-centered priorities and validated instruments. We aimed to prioritize key outcomes and propose suitable measurement tools to improve the quality, consistency, and relevance of regional anesthesia research. Methods We conducted a multiround Delphi process, including two electronic voting rounds, a multiday in-person meeting, and a patient panel. Experts and patients evaluated existing and proposed outcomes for importance, validity, and relevance. Outcomes reaching ≥70% agreement were prioritized, and appropriate measurement instruments were identified. Results Thirty-two experts and three patients participated. Across three Delphi rounds, 10 outcomes were prioritized for future regional anesthesia research: seven efficacy outcomes (pain scores; opioid consumption; Brief Pain Inventory; functional outcomes; cognitive function; length of stay; block duration); two multidimensional outcomes (quality of recovery and development of a regional anesthesia-specific quality-of-recovery instrument); one safety outcome (chronic postsurgical pain). Patients prioritized cognitive recovery, function, chronic pain, and pain scores. Conclusions This consensus-based, patient-centered framework defines the core priorities for future regional anesthesia and acute pain research. Future work should focus on developing and validating a regional anesthesia-specific quality-of-recovery instrument, refining multidimensional measures such as functional recovery, cognitive outcomes, and the Brief Pain Inventory, and standardizing the reporting of chronic pain and opioid-related outcomes. Adoption of these priorities will enhance methodological consistency, comparability, and patient relevance in future clinical trials.

Background Immune-related adverse events (irAEs) remain largely unpredictable, potentially affecting multiple organ systems and occurring at almost any point during and even occasionally after immune checkpoint inhibitor (ICI) treatment. To identify populations at risk for these immune-mediated toxicities, we analyzed genetic characteristics and immune markers associated with clinically significant irAEs. Methods We carried out a genome-wide association study on 373 white patients receiving ICI treatment. We identified single nucleotide polymorphisms associated with irAEs. Blood cytokine profiling and peripheral blood mononuclear cell RNA sequencing were performed at pretreatment baseline and 6–8 weeks after ICI initiation. Findings were validated in two external cohorts. Results We identified genetic haplotypes in VWA8 (Von Willebrand Factor A Domain Containing 8) , OSBPL6 (Oxysterol Binding Protein Like 6), and ADAMTS9-AS2 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif 9 Antisense RNA 2) associated with grade ≥2 irAEs. Patients carrying risk haplotypes for one or more genes exhibited significantly greater rates of grade ≥2 (OR 3.02; 95% CI 1.83 to 5.02; p<0.001), grade ≥3 (OR 3.59; 95% CI 1.93 to 6.64; p<0.001), and multiple type irAE (OR 2.60; 95% CI 1.53 to 4.39; p<0.001). Serum CCL3 levels were significantly elevated in individuals carrying risk haplotypes (p=0.03). Gene expression analysis demonstrated activated autoimmune and inflammatory pathways in the genetic risk group. Conclusions Novel polymorphisms in VWA8, OSBPL6, and ADAMTS9-AS2 may impact immune pathways, promote inflammation, potentiate autoimmune phenotypes, and convey risk of irAE in ICI-treated patients.

Abstract The tumor landscape of pancreatic ductal adenocarcinoma (PDAC) is refractory to conventional photon radiotherapy (RT) because of a fibrotic tumor microenvironment (TME) that promotes chronic hypoxia and reduced immune surveillance. The radiobiological factors unique to carbon ion RT (CIRT), such as high linear energy transfer and less dependence on oxygen, make it well-suited to overcome the PDAC TME. In this study, we utilized clonal syngeneic KPC pancreatic tumor cell lines and tumors to examine this postulate and to identify underlying factors that affect the response of PDAC to CIRT. Although KPC cell lines exhibited radiobiological effectiveness greater than 3, subcutaneous tumors in the mouse hind leg showed lower radiobiological effectiveness—1.3 based on quintupling time—at a linear energy transfer between 70 and 80 keV/μm. Four days after CIRT, we observed widespread transcriptomic changes in the tumor immune microenvironment, suggesting increased infiltration of antitumor immune cells and elevated expression of antitumor T-cell cytokines, MHC class I molecules, and co-stimulatory signals. Fewer immunologic changes were observed following photon irradiation. By 7 days after CIRT, tumor-supportive transcriptomic programs characterized by protumor cytokines, M2 macrophages, and cancer-associated fibroblasts emerged, promoting resistance and limiting the durability of tumor growth delay. These findings suggest that CIRT may offer a favorable platform compared with conventional photon RT for combining with immunotherapies. Furthermore, these data highlight the risk of using in vitro survival data alone in treatment planning and indicate that underlying TME factors affect the response of PDAC in vivo.

Study Design: Retrospective cohort analysis. Objective: To determine the effect of long-segment posterior cervical decompression and fusion (PCDF) on perioperative changes in vertebral Hounsfield Units (HUs) and the impact of these changes on radiographic outcomes and fusion status. Summary of Background Data: Low preoperative CT HUs have been associated with adverse outcomes after spinal fusion, including hardware complications and reoperation. No existing studies have investigated the preoperative to postoperative change in HUs after cervical spinal fusion. Stress shielding may decrease bone quality within the fusion construct. Whereas, altered junctional loading and increased segmental mobility may precipitate bony hypertrophy in the terminal and adjacent levels. Methods: All adult patients who underwent C2-T2 PCDF for myelopathy/ myeloradiculopathy at an academic center between 2013 and 2020 were retrospectively identified. Preoperative and postoperative HUs were assessed on axial CT images in the cranial, middle, and caudal C2, C6, T2, and T3 vertebral bodies, outside of the region of instrumentation and artifact by 2 independent reviewers. Paired t test compared preoperative to postoperative changes in HUs. Preoperative and long-term postoperative cervical alignment, fusion, and revision rates were assessed. Univariate and regression analysis compared patient factors and outcomes between groups with perioperative increase versus decrease in vertebral HUs. Results: One hundred patients were included. The average preoperative to postoperative change in HUs in the C2, C6, T2, and T3 vertebral bodies were −19.80 (P=0.008), −52.63 (P<0.001), 15.15 (P=0.014), and 9.41 (P=0.346), respectively. Perioperative increase in C2 HUs was predictive of increased postoperative distal junctional angle (β=3.41, P=0.048) and increased T1–T4 kyphosis (β=6.50, P=0.003). Perioperative increase in C6 HU predicted pseudoarthrosis (fusion odds ratio: 0.19, P=0.007). Conclusions: Significant perioperative decreases in C6 HUs within a long-fused construct may demonstrate stress shielding. The significant association between greater distal kyphosis and an increase in C2 HUs may be attributed to a stress riser effect. Level of Evidence: Level III.

501 Background: Targeted treatment options have significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL), but oncology healthcare professionals (HCPs) who provide care for fewer numbers of patients with CLL are challenged to remain current with continuously changing treatment paradigms. To assess ongoing educational needs, we analyzed the treatment choices made by HCPs in an online survey for select cases of poor-prognosis CLL and compared these with the choices of experts in CLL treatment for the same clinical scenarios. Methods: As part of a CME program, HCPs could access an online algorithm to enter specific characteristics of a CLL case scenario and receive treatment recommendations from 5 US-based CLL experts. Experts made recommendations in July 2024 for 146 possible case patients built into the algorithm. After entering their case characteristics, HCPs were asked to enter their planned treatment prior to viewing the expert recommendations. We compared expert and HCP treatment choices across various case scenarios that were entered into the algorithm, with a focus on previously untreated CLL with del(17p)/mutated TP53 or R/R CLL. Results: Between August 2024 and February 2025, 346 cases were entered into the algorithm by 174 HCPs. Among responding HCPs, 38% were based in the UK/EU, 24% in the US, and 10% in Asia; 62% treated ≤10 patients with CLL per month and 49% sought recommendations for a specific patient in their practice. Among 231 cases of previously untreated CLL entered, 91 (39%) sought recommendations for del(17p)/mutated TP53 disease. For cases with no major comorbidities and previously untreated CLL with del(17p)/mutated TP53 , all experts recommended acalabrutinib or zanubrutinib; in 19 cases submitted by HCPs practicing in locations where second-generation BTK inhibitors (BTKi) are approved for CLL (including the US, EU, and Japan), 58% planned 1 of these treatments for this case scenario, 17% planned ibrutinib-based therapy, and 11% planned venetoclax-based therapy. Among case scenarios requiring third-line therapy after progressing with 2 regimens including a covalent BTKi and venetoclax plus an anti-CD20 Ab (with progression <2 years after completing treatment), all experts would recommend a noncovalent BTKi (eg, pirtobrutinib), with 1 expert indicating they would also consider CAR T-cell therapy. For the same case scenario among 6 US-based HCPs, 1 planned pirtobrutinib and 3 planned CAR T-cell therapy. Overall, after reviewing expert recommendations, 61% of HCP respondents whose planned treatment differed from the experts indicated that they would change their approach, and 20% indicated barriers to implementing the recommendations. Conclusions: Our findings provide insight into potential educational needs among HCPs who manage patients with CLL, suggesting that targeted expert-led education could benefit these HCPs.

ABSTRACT Introduction Children with hepatoblastoma (HB) and other solid tumors frequently undergo intraoperative blood transfusion (IBT) with unknown impact on oncologic outcomes and scant data to guide transfusion in this population. This study tested the hypothesis that IBT is associated with poorer survival in children with HB. Methods A multicenter retrospective observational study of patients aged <18 years with HB who underwent primary tumor resection, including liver transplantation, from 2010 to 2019 was performed at 19 institutions. The association of IBT with risk of recurrence and death were determined using propensity score reweighted (PSR) Cox proportional hazards regression analyses. Results There were 338 patients identified who met inclusion criteria and had sufficient data for inclusion. Of those, 257 (76%) received IBT, including 253 (98%) who received packed red blood cells (pRBC), 84 (33%) who received plasma, and 28 (11%) who received platelets. IBT was associated with higher pretreatment extent of disease ( p < 0.001), presence of annotation factors (+VPEFR: 50%, n = 129 vs. 37%, n = 30, p = 0.035), and complex resections (extended, meso‐, or total hepatectomy: 54%, n = 139 vs. 27%, n = 22, p < 0.001); these differences were mitigated after applying propensity score weighting. Patients who received IBT had greater postoperative hemoglobin (g/dL) (median 10 (I8–11) vs. 9 (8–10), p = 0.013) and required more postoperative plasma and platelet transfusions ( p < 0.05). Median follow‐up was 4.4 (2.0–8.3) years. Compared with non‐IBT patients, those with IBT had higher incidence of death (PSR HR 2.35, 95% CI 1.10–5.02). Recurrence did not significantly differ across groups (PSR HR = 0.82, 95% CI 0.45–1.48). Conclusion IBT was associated with greater hazard of death. Postoperative hemoglobin levels suggested that unnecessary transfusions occurred and a pRBC‐focused approach to IBT led to coagulopathy. Development of optimal transfusion strategies for HB are needed to minimize unnecessary transfusions.

Abstract Despite significant therapeutic advances in multiple myeloma (MM), outcomes in patients with plasma cell leukemia (PCL) remain dismal. We conducted a multicenter retrospective analysis of patients with PCL who were treated with the B-cell maturation antigen–directed chimeric antigen receptor T-cell (CAR-T) products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). We identified 34 patients; 19 patients received ide-cel and 15 received cilta-cel. With a median follow-up of 11.9 months, the overall median progression-free survival (mPFS) was 9.0 months (95% confidence interval [CI], 4-15) and the median overall survival (mOS) was 13.0 months (95% CI, 8 to not estimable [NE]). The 1-year cumulative incidence of progression or death was 72%, and the 1-year cumulative incidence of death was 47%. Patients who received cilta-cel had a longer mPFS (19.0 months vs 6.0 months) and mOS (&gt;23 months [NE] vs 9.0 months) when compared with those treated with ide-cel. Similarly, the 1-year cumulative incidence of disease progression or death was 37.5% (95% CI, 17.4-68.5) with cilta-cel, whereas all patients treated with ide-cel progressed or died within 12 months of infusion. The rates of hematologic and nonhematologic toxicities were similar between patients treated with cilta-cel and those treated with ide-cel and were consistent with those reported in patients with MM. In this first multicenter study that evaluated patients with PCL who were treated with standard-of-care CAR-T products, we show that CAR-T is safe, feasible, and associated with improved outcomes when compared with historic standards.

Abstract The cumulative impact of baseline comorbidities on outcomes of chimeric antigen receptor T-cell (CAR-T) therapy is not well established. Therefore, we developed and validated a Cellular Therapy Comorbidity Index (CT-CI) to predict outcomes following CD19-directed CAR-T therapy for large B-cell lymphoma (LBCL). Patients aged 18 or older receiving commercial CAR-T therapy for LBCL during 2017 to 2020 were selected from the Center for International Blood and Marrow Transplant Research registry. Patients were randomly assigned to training or validation cohorts. Comorbidities given weighted scores comprised the CT-CI, which was then validated for overall survival (OS) prognostication. A total of 1916 patients from 97 medical centers were included, with a median age of 64 years (19-91 years). About 70% of patients had comorbidities, such as cardiac disease (12%); diabetes (14%); hepatic dysfunction (mild, 8%; moderate to severe, 2%); psychiatric disturbance (18%); and pulmonary dysfunction (moderate, 15%; severe, 12%). The CT-CI was calculated, stratified patients in 3 categories, and was associated with increased mortality. Patients with higher CT-CI scores had worse OS (CT-CI 1: hazard ratio [HR], 1.37 [95% confidence interval [CI], 1.16-1.62; P&lt; .001]; CT-CI 2: HR, 1.49 [95% CI, 1.17-1.89; P = .001]; CT-CI ≥ 3: HR, 2.55 [95% CI, 1.90-3.42; P&lt; .001]). Higher CT-CI scores predicted treatment-related mortality and relapse. There was no correlation between the CT-CI score and CAR-T–related toxicities. The novel CT-CI score stratifies the effect of patient comorbidities on survival after CAR-T therapy and can be used for clinical decision-making and treatment selection in high-risk populations. However, comorbidities and fear of increased toxicity should not preclude patients from this effective therapy.