Citations

PURPOSE Adjuvant endocrine therapy (ET) improves overall survival (OS) in estrogen receptor (ER)–positive early-stage breast cancer (BC). However, the benefit of ET for those with ER-low BC (ER 1%-10%) is unclear. METHODS Using the National Cancer Database, we studied patients with high-risk stage I to III, ER-low BC (defined as immunohistochemistry 1%-10%) who received (neo)adjuvant chemotherapy and did or did not initiate ET. OS was analyzed with ET initiation as a time-dependent covariate using Cox proportional hazards regression. RESULTS Of 10,362 patients with stage I to III ER-low BC, 7,018 received chemotherapy and met inclusion criteria. ET omission was 42% at 12 months and more common in patients with tumors that were progesterone receptor–negative, human epidermal growth factor receptor 2–negative, higher-grade (grade 2/3) and higher Ki-67 (≥20%; all P < .001) and those who received neoadjuvant chemotherapy (NAC; P < .001). With a median follow-up of 3 years, 586 deaths were observed. In a multivariable analysis, ET omission was associated with a higher risk of death (hazard ratio [HR], 1.23 [95% CI, 1.04 to 1.46]; P = .02), with a greater impact in those with higher ER levels: ER 1%-5% (HR, 1.15 [95% CI, 0.91 to 1.45]; P = .24) versus ER 6%-10% (HR, 1.42 [95% CI, 1.00 to 2.02]; P = .048). Among patients treated with NAC (n = 4,377, 62%), ET omission was associated with worse OS in those with residual disease (RD; HR, 1.26 [95% CI, 1.00 to 1.57]; P = .046) but not in those who achieved a pathologic complete response (HR, 1.06 [95% CI, 0.62 to 1.80]; P = .84). CONCLUSION In ER-low, early-stage BC, ET omission is associated with significantly worse OS, especially in patients with RD after NAC and those with higher (6%-10%) ER levels. Until prospective data are available, patients with ER-low BC should be counseled regarding the potential benefit of ET.

AbstractObjectiveThis study aims to evaluate the impact of parity on the severity and recurrence rates of idiopathic subglottic stenosis (iSGS) in premenopausal females.Study DesignA retrospective cohort study.SettingTwo tertiary care centers from 2002 to 2024.MethodsWe analyzed premenopausal iSGS patients under 40 years who underwent balloon dilation or laser wedge excision. Clinical features, including demographics and pregnancy history, were examined. Recurrence rates between nulliparous and parous patients were compared using Poisson regression, adjusting for age and follow‐up duration. Linear regression assessed the relationship between pregnancy and iSGS recurrence.ResultsForty‐eight patients were included, with 36 parous and 12 nulliparous. Adjusting for age and follow‐up, the mean recurrence rate was 2.6 times higher in parous patients (95% confidence interval [CI]: [1.5, 4.8], P = .0008). Each additional pregnancy was associated with 0.81 additional recurrences (95% CI: [0.05, 1.57], P = .0375). No significant differences in surgery‐free time were observed between groups.ConclusionParity and pregnancy significantly increase the risk of iSGS recurrence, although they do not accelerate subsequent recurrences. Health care providers should counsel women of childbearing age about these risks in family planning discussions, emphasizing shared decision‐making regarding potential surgical interventions.Level of evidence3.

Abstract ZUMA-8 evaluated the safety of brexucabtagene autoleucel (brexu-cel), a CD19-directed autologous chimeric antigen receptor (CAR) T-cell immunotherapy, for patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Patients with ≥2 prior lines of therapy (including a Bruton tyrosine kinase inhibitor) underwent leukapheresis, optional bridging therapy, and conditioning chemotherapy (fludarabine/cyclophosphamide) before infusion of 1 × 106 (cohort 1) or 2 × 106 (cohort 2) anti-CD19 CAR T cells per kg. Patients in cohort 3 (low tumor burden), and cohort 4A (postibrutinib) received 1 × 106 cells per kg. Fifteen patients, median age of 63 years (range, 52-79), were treated in cohorts 1 (n = 6), 2 (n = 3), 3 (n = 3), and 4A (n = 3). Median follow-up was 24.3 months. One dose-limiting toxicity was observed in cohort 3 (grade 4 cytokine release syndrome). Grade ≥3 neurologic events occurred in 3 patients (20%). Seven of 15 patients responded (overall response rate, 47%; complete response [CR], 7%), including all 3 patients in cohort 3 (1 with CR). CAR T-cell expansion occurred in 4 patients (27%), with an apparent weak inverse correlation with absolute lymphocyte count before apheresis. Brexu-cel had no new safety signals in R/R CLL. CAR T-cell expansion and responses occurred in patients with low tumor burden. This trial was registered at www.clinicaltrials.gov as #NCT03624036.

Background Orbital decompression is an essential tool for reducing proptosis in thyroid eye disease (TED), yet the impact of surgical approach and preoperative factors on outcomes remains uncertain. Objective To compare proptosis reduction following different orbital decompression techniques, identify additional risk factors that may play a role in surgical orbital decompression outcomes, and develop clinical decision-making recommendations based on these results. Methods A retrospective analysis was performed on TED patients who underwent endoscopic medial wall, orbital floor, and/or open lateral wall decompression. We evaluated the influence of preoperative comorbidities, anatomic and laboratory values, and surgical approach on postdecompression Hertel exophthalmometry outcomes. Results Analysis encompassed 130 orbits from 80 patients, 83% female, 48 with preoperative diplopia, and mean age of 54.4 years. Preoperative Hertel measurement was predictive of extent of proptosis reduction ( P < .0001), indicating that higher initial Hertel measurement predicts greater absolute reduction following surgical intervention. Surgical technique correlated with outcome on univariate analysis ( P = .04), but not multivariate ( P = .13) analyses. When categorized into preoperative Hertel ranges, combined endoscopic medial and open lateral wall decompression resulted in mean proptosis reduction of 3.13 mm for range 20.01 to 24 mm and 3.85 mm for range 24.01 to 28 mm. Three-wall decompression resulted in mean proptosis reduction of 2.49 mm for and 3.84 mm for these ranges, respectively. Variables such as smoking, body mass index, orbital wall height, and TRAb level, did not affect outcomes. Nine patients had new onset diplopia. Conclusions Preoperative Hertel exophthalmometry is the strongest predictor of proptosis reduction following orbital decompression in TED. Surgical technique appears to be less impactful on outcome than expected. Surgical decision making should be individualized based on patient goals; these findings can be used to achieve proptosis reduction and limit the risk of new onset diplopia.

Gastric cancer is a significant global health concern, with CDH1-associated gastric cancer representing a small but important subset of cases. Historically, individuals with CDH1 pathogenic germline variants were advised to undergo prophylactic total gastrectomy due to the high reported risk of gastric cancer and the limited sensitivity of upper endoscopy in detecting signet ring cell carcinoma (SRCC). However, emerging data suggest that the cumulative lifetime risk of advanced gastric cancer among CDH1 germline pathogenic variant carriers is lower than previously thought, and early-stage SRCC detected on endoscopy does not necessarily indicate imminent—or even eventual—progression to advanced cancer. The near-universal presence of T1a SRCC in gastrectomy specimens from asymptomatic CDH1 pathogenic variant carriers calls into question the reflexive recommendation for gastrectomy, including upon detection of SRCC during surveillance. Furthermore, the morbidity and quality-of-life impact associated with total gastrectomy require careful consideration. Active endoscopic surveillance has shown promise as an alternative management strategy for gastrectomy in patients lacking indicators of >T1a SRCC, though current data are limited by short follow-up periods and selection bias. This review synthesizes recent findings on the natural history of CDH1-associated gastric cancer and evaluates the risks and benefits of gastrectomy versus active endoscopic surveillance, with the goal of helping clinicians provide personalized and evidence-based recommendations for patients with CDH1 pathogenic variants.

Ewing sarcoma and osteosarcoma constitute 36% of all primary bone cancers. However, these 2 subtypes represent the most commonly diagnosed bone cancer types in the pediatric and adolescent population. Although still largely unknown, certain genetic mutations, rearrangements, and/or predisposition syndromes likely play a role in the pathogenesis of bone cancer. Osteosarcoma may also develop as a direct result of the long-term side effects of radiation therapy. With the implementation of a multimodality approach to treatment, including multiagent neoadjuvant and adjuvant chemotherapy regimens, targeted therapy options, surgery, and radiation, individuals with Ewing sarcoma and osteosarcoma are showing higher cure rates and improved overall survival. The NCCN Guidelines for Bone Cancer provide a consensus and evidence-based framework for the workup, management, and surveillance of local and recurrent/metastatic disease.