6-month Survival Research Articles

The Impact of Coronary Ischemia Assessment on Outcomes in Those With Scar-Dependent Ventricular Tachycardia.

Guidance and outcomes of coronary ischemia assessment (IA) in those with structural heart disease (SHD), presenting with monomorphic ventricular tachycardia (MMVT) is unclear. To assess the impact of IA on arrhythmic and non-arrhythmic outcomes in those with SHD. Patients presenting with MMVT over a 6-year period to a tertiary center were retrospectively analyzed. Propensity score-matched analysis was performed comparing those undergoing IA to those who did not. The primary endpoint was a composite of VT recurrence, appropriate ICD therapy, heart failure hospitalization, and death. Secondary analysis of the individual components of the composite was performed. Kaplan-Meier, univariate and multivariate analysis was performed to compare the two groups and derive predictors of poor outcomes. Two hundred and seventeen patients (57.6% ICM) were analyzed. 55.8% underwent IA. Following propensity score-matching, 120 patients remained. At 12 months, freedom from the primary endpoint was 68.3% of those undergoing IA versus 43.3% who did not, p < 0.001, multivariate HR 0.56 (0.34-0.92). This was driven by a reduction in all-cause mortality, with a 12-month survival of 98.3% in those undergoing IA versus 86.5% in those not undergoing IA (p < 0.01). Coronary intervention was associated with a significantly higher event-free 12-month survival compared to those who did not undergo intervention (82.4% vs 51.5%, respectively, p = 0.01). Patients with SHD presenting MMVT who undergo an IA have significantly improved freedom from VT recurrence, appropriate ICD therapies, HF hospitalization, and death compared to those who do not, driven by a reduction in mortality.

Impact of water physicochemical properties on the survival of Oncomelania hupensis snails, the intermediate host of Schistosoma japonicum.

Schistosoma japonicum, the causative agent of schistosomiasis, heavily relies on its single intermediate host, the Oncomelania hupensis snail, for its life cycle. Controlling these snails effectively plays a pivotal role in curbing the transmission and prevalence of this disease. While prior research has extensively investigated the impact of environmental factors such as temperature and vegetation on snail survival, growth, and reproduction, the contribution of water physicochemical properties has been notably underexplored. This study presents laboratory experiments designed to comprehensively explore the influence of water physicochemical properties on snail survival, offering valuable insights into environmental factors for more precise predictions of snail distribution. We meticulously conducted laboratory snail survival experiments using water from different sources (river water/tap water), and employed a statistical approach amalgamating principal component analysis with Cox regression to preliminarily investigate the effects of different water physicochemical properties on the survival of snails. Our analysis indicates that after a 6-month laboratory snail survival experiment, the survival rate in the tap water group was significantly higher than that in the river water group for infected snails (χ2 = 7.74, p = 0.005), while the difference in survival rates for non-infected snails was not statistically significant (χ2 = 0.61, p = 0.434). The Principal Component-Cox regression analysis revealed that in the infected snail group, total phosphorus, pH value, five-day biochemical oxygen demand, conductivity, and nitrite were protective factors for snail survival, while phosphate and total nitrogen were risk factors. In the non-infected snail group, total phosphorus, pH value, five-day biochemical oxygen demand, conductivity, and nitrite were protective factors for snail survival, and total nitrogen, ammonia nitrogen, phosphate, and nitrate were risk factors. This study underscores the substantial impact of water quality's physicochemical properties on snail survival. The effects of water quality on snails are complex, and maintaining an appropriate level of organic matter content and controlling the pH value at a weak alkalescency level prove beneficial for snail survival. These findings hold significant promise for advancing our understanding of snail-borne diseases and optimizing control strategies.

Phase I/II study of trifluridine/tipiracil plus XB2001 versus trifluridine/tipiracil in metastatic colorectal cancer.

Aim: Trifluridine/tipiracil-bevacizumab is a standard of care in metastatic colorectal cancer (mCRC) after chemotherapy failure. We aim to assess the addition of XB2001 (anti-IL-1 alpha monoclonal antibody) plus trifluridine/tipiracil-bevacizumab in mCRC refractory to standard chemotherapy.Methods: This multicenter, randomized, double blind, non-comparative Phase I-II study (ClinicalTrials.gov NCT05201352) will assess the efficacy and safety of trifluridine/tipiracil-bevacizumab and XB2001 in patients with mCRC previously treated for metastatic disease by chemotherapy treatment including oxaliplatin, irinotecan, 5-FU, antiangiogenic and/or anti-EGFR if indicated. Primary end point of Phase I is the safety according to the Maximum Tolerated Dose (MTD) of XB2001. Primary end point of Phase II is the efficacy of trifluridine/tipiracil-bevacizumab+XB2001 in term of 6-month overall survival. Ancillary analysis will be performed.

To Use or Not to Use: Temozolomide in Elderly Patients with IDH Wild-type MGMT Promoter Unmethylated Glioblastoma Treated with Radiotherapy.

To identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated MGMT promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT). Newly diagnosed patients with IDH wild-type eGBM-unmethylated treated with RT were included in this multicenter analysis (n=182). RT dose was 45 Gy in 15 fractions (62.3%), 60 Gy in 30 fractions, or 61.2 Gy in 34 fractions. For patients treated with RT plus TMZ (60.4%), TMZ was administered concurrently with RT, followed by six adjuvant cycles. The primary endpoint was overall survival. During a median follow-up of 11.3 months for survivors, the median survival was 12.2 months. The median survival duration significantly improved with the addition of TMZ to RT compared with that with RT alone (13.6 months vs. 10.5 months, p=0.028). In the multivariable analysis adjusted for clinical, radiological, and genetic biomarkers, the addition of TMZ significantly improved overall survival (hazard ratio, 0.459; p=0.006). In subgroup analysis, median survival was especially improved by 4-5 months in patients with residual disease (p<0.001), Karnofsky Performance Status ≥60 (p=0.033), and age ≤75 years (p=0.090). A significant benefit of TMZ was noted only in patients with two or three of the above factors (median survival, 14.1 months vs. 10.5 months, p=0.014). The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.

Neoadjuvant chemotherapy with FLOT scheme in surgical treatment of gastric cancer: short- and long-term outcomes. A retrospective cohort study

Aim. To compare the results of surgical treatment of patients with gastric adenocarcinoma and esophagogastric junction cancer (EGJC) who received neoadjuvant chemotherapy (NCT) FLOT with primary operated patients. Materials and methods. A retrospective cohort study included 177 patients who underwent radical surgical treatment at the Burdenko Faculty Surgery Clinic of Sechenov University for gastric cancer (GC) and/or EGJC Sievert Type II–III in the period from January 2018 to December 2022. The main group consisted of patients (n=28) who received NCT FLOT. Patients in both groups did not statistically significantly differ in average age (p=0.110), ASA status (p=0.541), ECOG status 0–3 (p=0.12), localization (p=0.063), depth of invasion (p=0.099) and histological structure of the tumor (p=0.787). In the main group, more patients with lesion of the regional lymph nodes were expected (p0.001). According to the most significant indicators [postoperative complications, the presence of a "positive" edge of resection (R1), recurrence and/or progression of GC], we performed a quasi-randomization by the matching procedure, taking into account the selection of the nearest neighbors. Results. In 92.9% of patients in the main group and in 94.9% of the control group, R0 resection (p=0.750) was achieved. The number of removed lymph nodes was statistically significantly higher in the main group (average 26 vs 21; p=0.010). There was no difference in intraoperative blood loss (p=0.294) and hospital stay (p=0.992). The average duration of surgery in the main group was 319 minutes, compared to 250 minutes in the control group (p0.001). In the early postoperative period, the total number of complications (CD I–IV) was higher in the main group (p=0.031), however, there was no difference in the number of small (CD I–II; p=0.094) and significant (CD III–V; p=0.142) complications. Postoperative mortality in the first 30 days after surgical treatment was 3.6 and 2.5% in the main and control groups, respectively (p=0.764). The overall 6-month survival rate in the control group was 95.9% vs 90.9% in the main group, and the 12-month survival rate was 88.8% vs 75.7%, respectively. The reccurence-free 6-month survival rate in the control group was 96%, in the main group – 100%; the reccurence-free 12-month survival rate in the control group was 92.1%, in the NCT group – 93.3%. Conclusion. NCT FLOT in the treatment of GC and EGJC Sievert Type II–III does not increase the level of intraoperative blood loss, the number of postoperative complications and the duration of hospitalization. The 6-month and one-year survival rates did not differ in the two groups. Considering that the majority of patients in the NCT group belonged to the cN+ category, with an initially less favorable treatment prognosis, it can be assumed that comparable survival results were achieved thanks to NCT.

NIMG-08. IMAGING FINDINGS AND PROGNOSTIC FACTORS IN DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT

Abstract INTRODUCTION Diffuse hemispheric glioma, H3 G34-mutant (DHGs), are a newly categorized tumor in pediatric-type diffuse high-grade gliomas in the 2021 World Health Organization classification, with a poor prognosis. DHGs has been reported to occur in less than 1% of all gliomas, but prognostic factors have not been fully investigated in previous studies due to small sample sizes. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS We searched Medline through the PubMed database using two search terms: “G34” and “glioma”, between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan–Meier curves and logistic regression. RESULTS A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS of all cases was 14.4 months. Univariate logistic regression analysis with 12-month OS as the outcome showed that the MI-positive group had a significantly higher mortality than that in the MI-negative group, and the gross total resection achieved group had a significantly lower mortality than that in the group that underwent biopsy alone. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS Similar to glioblastomas, DHGs have a poor prognosis if they invade deep structures or the contralateral cerebrum; however, safe and maximal tumor resection may prolong survival.

CTNI-49. PRECISION MEDICINE CLINICAL TRIAL FOR ADULT PATIENTS WITH RECURRENT GLIOBLASTOMA

Abstract Salvage therapies for recurrent glioblastoma (rGBM) have limited efficacy, with median overall survival of 9 months (OS-9) and 6-month progression-free survival (PFS-6) of 10-25%. Given GBM’s molecular heterogeneity, targeting a single molecular abnormality in isolation has consistently failed as a strategy, and precision combination approaches are needed. An initial 15-patient cohort evaluated the feasibility and safety of treating patients with rGBM with an individualized treatment regimen; we added a second 15-patient expansion cohort to improve the power of preliminary efficacy assessment. Patients underwent clinically indicated surgery with genomic profiling using the UCSF500 targeted DNA sequencing panel. Each personalized treatment regimen combined up to 4 FDA-approved drugs, including one cytotoxic agent, as determined by consensus discussion at an individualized molecular tumor board for each patient. Bevacizumab was not utilized in these combinations. The primary objective of the combined 30-patient cohort was efficacy of individualized treatment regimens by OS-9; secondary objectives included safety and additional efficacy measures including PFS-6. Median age was 53 years (range 32-71). Of 30 patients, 18 were male, 23 were enrolled at first recurrence, 29 had IDH-wildtype glioblastoma, 1 had IDH-mutant astrocytoma, and 10 had MGMT promoter methylation. A total of 12 FDA-approved drugs were used in 18 combinations; the most common regimen prescribed was lomustine, afatinib, and abemaciclib (7; 23%,); second-most common was temozolomide, olaparib, and afatinib (4; 13%). OS-9 of the combined cohort was 70% (95% CI 0.55 – 0.89) and PFS-6 was 27% (95% CI 0.15 – 0.48), with median OS of 11.6 months (95% CI 9.7 – 16.7) and median PFS of 3.7 months (95% CI 2.0 – 5.5).While overall efficacy was modest, implementation of individualized treatment regimens in a timely fashion was safe and feasible for patients with surgically resectable rGBM. Analysis is ongoing to assess whether specific genomic profiles or treatment regimens were particularly efficacious.

CTNI-54. RESPONSE BY RANO2.0 CRITERIA IN ONC201 (DORDAVIPRONE)-TREATED PATIENTS WITH RECURRENT H3 K27M-MUTANT DIFFUSE MIDLINE GLIOMA

Abstract PURPOSE Response assessment in neuro-oncology (RANO) 2.0 is a recently established response assessment for glial tumors that is agnostic to WHO grade. This updated response assessment includes quantitative evaluation of enhancing and non-enhancing disease and recommendations to account for pseudoprogression. This analysis evaluated response to ONC201 by RANO2.0 in recurrent, H3K27M-mutant diffuse midline glioma (DMG), which was previously assessed by RANO-HGG/RANO-LGG (Arrillaga-Romany, JCO, 2024). METHODS Fifty patients with recurrent H3 K27M-mutant DMG were selected based on criteria designed with input from regulators to evaluate objective response to ONC201 monotherapy. Patients had contrast-enhancing, measurable, progressive disease, and were ≥90 days from radiation, with adequate washout from other anti-cancer therapies. Diffuse intrinsic pontine glioma, primary spinal tumors, leptomeningeal spread, or CSF-disseminating tumors were ineligible. Response was assessed using RANO2.0 criteria by two-party blinded independent central review. RESULTS Best response by RANO2.0 included one complete response (CR, 2.0%), nine partial responses (PR, 18.0%), and four minor responses (MR, 8.0%). Overall response rate (CR+PR+MR) by RANO2.0 criteria was 28.0% (n=14; 95%CI, 16-42). Disease control rate (CR+PR+MR+SD) was 40.0% (n=20; 26-55). Median duration of response was 10.4 months (95%CI, 7.4-15.4). Median time to response was 4.6 months (range, 1.6-15.9). 6- and 12-month progression free survival rates were 32.0% (95%CI, 19-47) and 27.0% (15-41), respectively. RANO2.0 response as a time-varying covariate was significantly associated with overall survival in a multivariate analysis considering baseline performance score, multiple enhancing target lesions, enhancing tumor size, and number of prior recurrences (HR [95%CI], 0.22 [0.08–0.58]; p=0.0023). Patients with an objective response by RANO2.0 were more likely to be alive at 12 (100%) and 24 (86%) months, have reduced corticosteroid usage, and have improved performance status. Responses occurred at a higher rate among patients with a higher performance score and fewer target lesions. CONCLUSIONS RANO2.0 assessment of ONC201-treated patients suggests durable and clinically meaningful efficacy in recurrent H3K27M-mutant DMG.

Inflammatory stress determines the need for chemotherapy in patients with HER2-positive esophagogastric adenocarcinoma receiving targeted and immunotherapy.

Anti-PD-1, trastuzumab, and chemotherapy are used in the treatment of patients with advanced HER2-positive esophagogastric adenocarcinoma (EGA), but long-term survival remains limited. Herein, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti-PD-1 nivolumab, trastuzumab, and FOLFOX chemotherapy (FOLFOX arm) in comparison to a chemotherapy-free regimen involving nivolumab, trastuzumab, and the anti-CTLA-4 ipilimumab (Ipi arm) in the first-line setting for advanced disease. The 12-month overall survival (OS) showed no statistical difference between the arms, with 57% OS (95% CI: 41%-71%) in the Ipi arm and 70% OS (95% CI: 54%-82%) in the FOLFOX arm. Crossing of the survival curves indicated a potential long-term benefit for some patients within the Ipi arm, but early progressors in the Ipi arm underlined the need for biomarker-guided strategies to optimize treatment selection. To this end, metabolomic and cytokine analysis demonstrated elevated levels of normetanephrine, cortisol, and interleukin 6 (IL-6) in immunotherapy-unresponsive patients in the Ipi arm, suggesting a role for systemic inflammatory stress in modulating antitumor immune responses. Patients with this signature also showed an increased neutrophil-to-lymphocyte ratio (NLR) that persisted in the Ipi arm, but not in the FOLFOX arm, and strongly correlated with survival. Furthermore, a low NLR characterized patients benefiting from immune- and targeted therapy without the need for additional chemotherapy. This data suggests that patient selection based on inflammatory stress-driven immune changes could help to customize first-line treatment in patients with advanced HER2-positive EGA to potentially improve long-term survival.

CNSC-62. DIFFERENTIAL SURVIVAL IMPACT OF TRASTUZUMAB DERUXTECAN IN HER2-POSITIVE VERSUS HER2-LOW BREAST CANCER PATIENTS WITH BRAIN METASTASES

Abstract BACKGROUND Brain metastases (BM) in breast cancer (BC) present significant treatment challenges, with varying outcomes based on HER2 expression. There is limited real-world evidence of outcomes with the use of trastuzumab deruxtecan (T-DXd) on survival in patients (pts) with HER2-low and HER2-positive (HER2+) MBC with BM. METHODS We conducted a retrospective cohort study using data from seven US-based health systems within the Guardian Research Network (GRN). We included pts treated with T-DXd from December 2019 to December 2023, classified as HER2-low (IHC 1+ or IHC 2+/HER2 FISH non-amplified) or HER2+ (IHC 3+ or HER2+ with FISH amplified). Survival analysis was performed using Kaplan-Meier curves and the log-rank test. RESULTS 125 pts with BCBM treated with T-DXd were included in the final analysis, of which 70 (56%) were HER2+ and 55 (44%) were HER2-low. The median age at BM diagnosis was 60.5 years (range 21.6 to 87.1 years). HER2 low pts had a higher prevalence of ER+ disease than HER2+ pts (81.9% vs. 55.7%, p=0.01). Most of these pts (≥75%) had received multiple prior lines of therapy. HER2+ pts with BM had a median overall survival (mOS) of 9.3 months (95% CI: 6.79-11.88), significantly longer than 4.3 months (95% CI: 1.89-6.82) in HER2-low pts (p &amp;lt; 0.001). At 6 months, OS for HER2+ pts with BM was 40% compared to 25% in HER2-low pts. At 12 months, OS for HER2+ pts was 20% compared to 10% in HER2-low pts. CONCLUSIONS This study represents the largest real-world evidence to date on the effectiveness of T-DXd in treating BM from breast cancer. HER2+ BCBM exhibited longer mOS and 12-month survival rates than pts with HER2-low disease, suggesting HER2 expression is crucial in determining T-DXd’s effectiveness. Future research should explore combination therapies and identify predictive biomarkers to optimize treatment strategies through clinical trials.

IMMU-04. G-AMINOBUTYRIC ACID DRIVES GLIOBLASTOMA IN FEMALES IN AN IMMUNE-DEPENDENT MANNER

Abstract Communication with a neuronal network and accumulation of myeloid-derived suppressive cells (MDSCs) support GBM growth and therapeutic resistance. GBM incidence and outcomes differ between males and females. We previously demonstrated that granulocytic (gMDSCs) drive GBM in females. However, a lack of understanding of the host factors regulating distinct MDSC subset function remains to be a major obstacle for therapeutically targeting these cells in GBM. In this study, we identified γ-aminobutyric acid (GABA) pathway as a modulator of gMDSC activity. gMDSCs from both healthy adults and glioma patients, expressed significantly higher levels of GABA receptor B1 (GABBR1) and GABA receptor B2 (GABBR2) compared to monocytic MDSCs (mMDSCs). On contrary, GABA receptor A (GABAAR) subunits were not expressed in either MDSC subtype. Given these differences, we investigated the effect of GABA on MDSC metabolism and found an increase in L-arginine metabolism specifically in female gMDSCs following GABA treatment while no significant metabolic changes were observed in any other groups. In MDSCs, L-arginine can be metabolized via nitric oxide synthase (NOS2) or Arginase-1 (Arg-1). While treatment with GABA or the GABBR agonist baclofen increased NOS2 production in specifically in female gMDSCs, Arg-1 was not affected. Mechanistically, baclofen enhanced gMDSC-mediated T cell suppression in females. In preclinical models of GBM, baclofen treatment resulted in a truncated survival only in immunocompetent female mice, which was reversed by pharmaceutical inhibition of NOS2. Clinically, female patients on GABA analogs (pregabalin, gabapentin) had significantly lower 12-month survival probabilities compared to control population. This effect was not observed in male patients. Conversely, inhibition of GABBR with CGP35348 prolonged survival in female GBM models and reprogramed the immunosuppressive tumor microenvironment. Collectively, these results highlight that GABA alters anti-tumor immune response in a sex-specific manner. These results support the future assessment of GABA pathway inhibitors as potential immunotherapy agents in GBM.

Predicting reprisal of solid cancer treatment and 60-month survival after Medical Intensive Care. A single-centre cohort study.

Our study aimed to identify relevant features associated with the reprisal of antineoplastic treatment in patients with solid cancers after unplanned admittance to the intensive care unit (ICU) and to assess 60th-month survival in patients with solid neoplasms admitted to the ICU. This single-centre retrospective study of critically ill patients with active cancers was performed over a 13-year period (2005-2018). Patients' characteristics, overall survival and antineoplastic treatment reprisal were extracted from digital medical files and compared. 134 patients were included in the study. Solid neoplasms were mostly localised to the head and neck (n=53) followed by lung cancers (n=29). Sepsis was the leading cause of ICU admission (62.1%) with 41/82 patients presenting with septic shock. Antineoplastic treatments were resumed in 40 patients. An age ≤60 years and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1 were found to be predictors for treatment reprisal, with odd ratios of, respectively, 2.83 (95%CI, 1.15-6.99) and 5.45 (95%CI, 2.01-14.82); area under the ROC curve of 72% (95%CI, 63-81%). Survival after the immediate discharge from the ICU was 101/134 (75%) and the 60-month survival rate was 29% and significantly higher in the treatment-reprisal group. Age and ECOG PS were found to be predictors for treatment reprisal in patients with solid neoplasms admitted to the ICU. The latter benefit from better long-term survival.

The Role of FLT3-ITD Mutation, PI3K/AKT Pathway, and Leukemia Stem Cells in D3A7 Induction therapy – the Outcomes of Adult Indonesian Patients with Acute Myeloid Leukemia

Objective. This cohort study aimed to examine the impact of the FLT3-ITD mutation on the downstream signaling pathway of PI3K/AKT pathway, the percentage of leukemia stem cells, and the survival of patients receiving D3A7 induction therapy. Method. Bone marrow mononuclear cells were collected from 20 adult AML patients who had completed D3A7 induction therapy at Cipto Mangunkusumo National General Hospital and Dharmais Cancer Hospital. FLT3-ITD gene mutation was examined by the PCR-sequencing method. Expression of phosphorylated PI3K and AKT was detected using the sandwich ELISA method. Flow cytometry was used for detecting the number of apoptosis and proliferation cells, and biomarkers of leukemia stem cells. Result. The expression levels of PI3K and AKT proteins were higher in FLT3-ITD, both in the mutant group compared to the non-mutation group, and in the patient group with treatment failure outcomes compared to the patient group with treatment response. The percentage of the leukemia stem cell population did not differ significantly between the FLT3-ITD mutation group and the wild type group, and between the treatment failure outcome group and the response outcome group. Conclusion. This study presents the important role of FLT3-ITD mutation via its downstream signaling (PI3K/AKT) in the outcome of D3A7 induction therapy. The FLT3-ITD mutation plays an important role in the 12-month survival of AML patients after D3A7 therapy. However, the outcome of D3A7 therapy and FLT3-ITD mutation were not associated with leukemia stem cells.

Equecabtagene Autoleucel in Patients With Relapsed or Refractory Multiple Myeloma

Equecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary. To evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion. The FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM. Enrollment began in April 2020, and patients who received eque-cel will be monitored for a minimum of 15 years following the infusion. As of September 2022, patients with heavily pretreated RRMM who received at least 3 prior courses of therapy from 14 centers were enrolled. Data were analyzed from April 2020 to September 2022. Patients received a single infusion of eque-cel at 1.0 × 106 CAR-positive T cells/kg after the lymphodepletion. Efficacy was the primary objective, and safety, pharmacokinetics, and pharmacodynamics were secondary objectives. Of 103 patients who received an eque-cel infusion, 55 (53.4%) were male, and the median (range) age was 58 (39-70) years. A total of 101 patients were evaluable for efficacy. At a median (range) follow-up of 13.8 (0.4-27.2) months, the overall response rate was 96.0% (97 of 101), with 74.3% (75 of 103) achieving a complete response or better. Among the 12 patients who had prior CAR T-cell treatment, 75% (9 of 12) achieved a response. The median progression-free survival was not reached, with a 12-month progression-free survival rate of 78.8% (95% CI, 68.6-86.0). A total of 96 patients (95.0%) achieved minimal residual disease negativity at a sensitivity threshold of 10-5. Adverse events were favorable: 96 of 103 patients (93.2%) experienced cytokine release syndrome (grade 1 to 2 in 95 patients [92.3%]) and 2 (1.9%) experienced immune effector cell-associated neurotoxicity syndrome (grade 1 to 2). All cases of immune effector cell-associated neurotoxicity syndrome and 94 of 96 cases of cytokine release syndrome resolved with treatment. Additionally, only 20 patients (19.4%) developed antidrug antibodies. Cellular kinetic analysis confirmed CAR-positive T cells in all patients, with the longest duration at 735 days. In this trial, eque-cel led to early, deep, and durable responses in patients with heavily pretreated RRMM with a manageable safety profile. Patients with prior CAR T-cell therapy also benefitted from eque-cel. Chinese Clinical Trial Registry Identifier: ChiCTR2000033946.

Temperature guided high and very high-power short duration ablation for atrial fibrillation treatment - The peQasus multicentre study.

Temperature-controlled high-power short-duration (HPSD) radiofrequency catheter ablation for pulmonary vein isolation (PVI) utilizing a novel ablation catheter (QDOT Micro) with real-time assessment of catheter tip temperature aims for safer, more effective and faster procedures. The peQasus study is a large European multicenter study set up to assess safety, acute efficacy and outcomes of temperature-controlled HPSD based PVI. The primary endpoints were safety, efficacy and 12-months freedom from atrial tachyarrhythmias. Additionally, two strategies namely very HPSD (90W for 4 seconds) only and a hybrid approach (HPSD with maximum of 50W and vHPSD) were compared. A total of 1,023 AF patients in 15 centers from 9 European countries received PVI with the QDOT. Complete PVI was successfully achieved in all patients. In 699/1023 (68.3%) the vHPSD only approach (vHPSD group) and in 324/(31.7%) patients the hybrid approach (hybrid group) was utilized. The mean procedure duration was 98.4±37.4 min (vHPSD: 88.2±34.9min, hybrid: 117.4±32.7min, p<0.001). The first pass isolation rate of all PVs was 64% (vHPSD: 62.6%, hybrid: 67.1%, p=0.187). Severe adverse events were observed in 1.7% (vHPSD: 1.6%, hybrid: 1.9%, p=0.746). 12-month arrhythmia-recurrence free survival was 77.1% (vHPSD: 76.8%, hybrid: 77.8%, p=0.241). In this large multicentre study temperature-controlled HPSD and vHPSD ablation via a novel ablation catheter provides safe and effective PVI with a relatively short procedure duration. Despite a shorter procedure time no differences in terms of safety and freedom from arrhythmia-recurrence were found irrespective of utilizing vHPSD or the hybrid approach.

Percutaneous transhepatic biliary drainage in patients with cholestasis following liver transplantation.

Biliary strictures are among the most common complications following liver transplantation (LT). If endoscopic retrograde cholangiography fails, percutaneous transhepatic biliary drainage (PTBD) may serve as an alternative approach. Description of clinical important short- and long-term outcomes as well as outcome prediction following PTBD after LT are scarce. We analyzed outcomes of 56 liver-transplanted adults with biliary complications receiving a PTBD. We described the safety and longitudinal laboratory changes. We analyzed as endpoints, incidence of biliary complications, need for surgical biliary revision/re-LT and overall-survival at 12- and 60-months. We used simple comparison tests accordingly and performed competing risk analysis and multivariate competing risk regression as well as log-rank test and cox proportional hazard regression for further analysis. PTBD procedures had a high technical success rate (98%) and tolerable safety profile. Multiple laboratory indicators improved during follow-up (37 patients with complete biochemical follow-up). Incidence of subsequent biliary complications was highly dependent on the nature of present biliary strictures (Anastomotic stricture (AS): adjusted SHR: 0.26, 95% CI: 0.09-0.78, p = 0.016). Need for surgical biliary revision/re-LT remained below 15%. 12-month survival was significantly better, if drainage into the small intestine was achieved at first attempt compared to completely external drainage (internal: 92.9 vs. external: 67.9%, p = 0.018). Patients with AS had a numerically higher long-term-survival and higher C-reactive-protein (CRP) and lower body-mass-index (BMI) at baseline were significantly associated with inferior short- and long-term-survival. PTBD for biliary complications following LT had a high technical success and a tolerable safety profile. Incidence of subsequent biliary complications was highly dependent on the nature of biliary strictures and increased mortality was found in patients with higher CRP, lower BMI and failure of initial PTBD internalization.

Emapalumab Treatment in Patients With Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis in the United States: A Retrospective Medical Chart Review Study.

Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-γ, approved for treating patients with primary HLH. REAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with one or more dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH. Fifteen of 105 patients (14.3%) had rheumatologic disease-associated HLH. Of these, nine (60.0%) had systemic juvenile idiopathic arthritis, and one (6.7%) had adult-onset Still disease. Median (range) age at HLH diagnosis was 5 (0.9-39) years. Most patients (9 of 15; 60.0%) initiated emapalumab in an intensive care unit. Emapalumab was most frequently initiated for treating refractory or recurrent (10 of 15; 66.7%) disease. Most patients received HLH-related therapies before (10 of 15; 66.7%) and concurrently with (15 of 15; 100.0%) emapalumab. Emapalumab-containing regimens stabilized or achieved physician-determined normalization of most laboratory parameters, including absolute neutrophil count and absolute lymphocyte count (13 of 14; 92.9%), chemokine ligand 9 (9 of 11; 81.8%), and platelets and alanine transaminase (11 of 14; 78.6%), and reduced glucocorticoid dose by 80%. Overall survival and 12-month survival probability from emapalumab initiation were 86.7%. Emapalumab-containing regimens stabilized or normalized most key laboratory parameters, reduced glucocorticoid dose, and were associated with low disease-related mortality, thereby demonstrating potential benefits in patients with rheumatologic disease-associated HLH.

Impact of quality of care on outcomes in survivors of stroke with aphasia: A linked registry and hospital data observational study

BackgroundThe impact of hospital care quality on patient outcomes in post-stroke aphasia remains unclear. We investigated the impact of nationally-endorsed acute stroke treatments on outcomes post-stroke, by aphasia status. MethodsPatient-level data from the Australian Stroke Clinical Registry (2009–2013) linked to national deaths, hospital emergency presentations and admissions data were used. Aphasia was identified for the index stroke event (ICD-10 diagnosis code R47.0). Impact of receiving an optimal stroke care bundle (stroke unit care, antihypertensive medication at discharge and discharge care plan) and an acute ischemic stroke (AIS) care bundle (stroke unit care, intravenous thrombolysis and aspirin within 48 h of admission) on outcomes were analysed using multivariable regression models with propensity score adjustment. ResultsThe study included 12,690 patients with a median age of 76, 54 % male, and 26 % with aphasia. Non-receipt of the optimal stroke care bundle was associated with worse survival, compared to optimal care, in people with aphasia (HR: 3.37; 95 % CI 2.10, 5.40; p < 0.05) and without aphasia (HR: 2.10; 95 % CI 1.19, 3.69; p < 0.05). Notably, the dose-response effect on survival was more pronounced in individuals with aphasia. In those who received the AIS care bundle, readmission within 12 months was greater in those without aphasia (vs aphasia, p-value interaction = 0.001), whereas survival was similar (p-value interaction = 0.731). ConclusionsSurvivors of stroke with aphasia who did not receive the optimal stroke care bundle, had worse survival at 12 months post-stroke. Ensuring eligible patients receive the optimal stroke care bundle is crucial for improving their 12-month survival.

Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study.

Patients with gastroesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastroesophageal cancer. We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastroesophageal adenocarcinoma following neoadjuvant chemotherapy and resection. VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastroesophageal adenocarcinoma at high risk of recurrence. Patients were randomised 1:1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg IV every 2 weeks plus ipilimumab 1 mg/kg IV every 6 weeks for 1 year. Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery. The primary endpoint was disease-free survival in the intent-to-treat population. Secondary endpoints included overall survival, loco-regional and distant failure rates and safety according to NCI-CTCAE v5.0. The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy). Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months (95% confidence interval [CI], 8.4-16.8 months) versus 20.8 months (95% CI, 15.0-29.9 months) for the chemotherapy group, HR 1.55 (95% CI, 1.07- 2.25, one-sided P=0.99). The 12-month disease-free survival rates were 47.1% and 64.0%, respectively. There were no toxicity concerns or excess early discontinuations. Nivolumab/ipilimumab did not improve disease-free survival compared to chemotherapy in patients with ypN+ and/or R1 gastroesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery.

Effectiveness of immune checkpoint inhibitors and other treatment modalities in patients with advanced mucosal melanomas: a systematic review and individual patient data meta-analysis

Mucosal melanomas (MM) are an aggressive subtype of melanoma. Given the rarity of this disease, the conduct of clinical trials is challenging and has been limited. Current treatment options have been extrapolated from the more common cutaneous melanoma even though MM is distinct in pathogenesis, etiology and prognosis. This is the first meta-analysis to comprehensively assess the efficacy of immune checkpoint inhibitors (anti-PD1 and anti-CTLA4) and other treatment modalities (targeted therapy such as KIT inhibitors and VEGF inhibitors, as well as radiotherapy) on survival outcomes in MM to develop clinical guidelines for evidence-based management. The protocol was prospectively registered on PROSPERO (PROSPERO ID: CRD42023411195). PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and Google Scholar were searched from inception until 25 July 2024, for all cohort and observational studies. Eligible studies included those with five or more participants with locally advanced or metastatic MM treated with anti-PD1, anti-CTLA4, VEGF inhibitors and/or KIT inhibitors. Titles and abstracts of potential articles were screened and full texts of all potentially eligible studies were retrieved and reviewed by two independent reviewers. Individual patient data (IPD) from published Kaplan-Meier curves were reconstructed using a graphical reconstruction method and pooled as a one-stage meta-analysis. A sensitivity analysis using a two-stage meta-analysis approach was conducted. Extracted outcomes included overall survival (OS) and progression-free survival (PFS). For each treatment arm, median survival time and 12-month survival proportion were estimated. Data from double-arm trials was pooled to estimate hazard ratios (HRs), ratios of restricted mean time lost (RMTL) and restricted mean survival time (RMST). From a total of 7402 studies, 35 eligible studies comprising a total of 2833 participants were included. Combined anti-PD1 and anti-CTLA4 therapy had the highest 12-month OS and 12-month PFS at 71.8% (95% CI: 67.6%, 76.2%, n=476) and 35.1% (95% CI: 30.5%, 40.4%, n=401) respectively, followed by anti-PD1 therapy alone (OS: 64.0% (95% CI: 61.4%, 66.7%, n=1399); PFS: was 28.3% (95% CI: 25.8%, 31.2%, n=1142), anti-PD1 and VEGF inhibitor combination therapy (OS: 57.1% (95% CI: 51.0%, 63.9%)), KIT inhibitors (OS: 48.2% (95% CI: 37.6%, 61.8%); PFS: 8.3% (95% CI: 3.7%, 18.7%)) and anti-CTLA4 therapy alone (OS: 33.3% (95% CI: 28.4%, 39.1%); PFS: 9.8% (95% CI: 5.9%, 16.5%)). In the double-arm studies, combination therapy with anti-PD1 and anti-CTLA4 had similar OS and PFS with anti-PD1 alone (OS: HR 0.856 (95% CI: 0.704, 1.04); RMTL ratio 0.932 (95% CI: 0.832, 1.044, P=0.225); RMST ratio 1.102 (95% CI: 0.948, 1.281, P=0.204); PFS: HR 0.919 (95% CI: 0.788, 1.07); RMTL ratio 0.936 (95% CI: 0.866, 1.013, P=0.100); RMST ratio 1.21 (95% CI: 0.979, 1.496, P=0.078)), however, anti-PD1 therapy alone had significantly better PFS than anti-CTLA4 alone (HR 0.548 (95% CI: 0.376, 0.799); RMTL ratio 0.715 (95% CI: 0.606, 0.844, P<0.001); RMST ratio 1.659 (95% CI: 1.316, 2.092, P<0.001)). Anti-PD1 therapy with radiotherapy versus anti-PD1 alone showed no significant difference (OS: HR 0.854 (95% CI: 0.567, 1.29); RMTL ratio 0.855 (95% CI: 0.675, 1.083, P=0.193); RMST ratio 1.194 (95% CI: 0.928, 1.536, P=0.168; PFS: HR 0.994 (95% CI: 0.710, 1.39); RMTL ratio 1.006 (95% CI: 0.87, 1.162, P=0.939); RMST ratio 0.984 (95% CI: 0.658, 1.472, P=0.939)). For the systemic treatment of MM, anti-PD1 is the best monotherapy. While combining anti-PD1 with other treatment options such as anti-CTLA4, VEGF inhibitors or radiotherapy might achieve better outcomes, these improvements did not reach statistical significance when evaluated by HR, RMTL and RMST ratios. This work was supported by theNational Medical Research CouncilTransition Award (TA20nov-0020),SingHealthDuke-NUSOncology Academic Clinical Programme (08/FY2020/EX/67-A143 and 08/FY2021/EX/17-A47), the Khoo Pilot Collaborative Award (Duke-NUS-KP(Coll)/2022/0020A), theNational Medical Research CouncilClinician Scientist-Individual Research Grant-New Investigator Grant (CNIGnov-0025), the Terry Fox Grant (I1056) and the Khoo Bridge Funding Award (Duke-NUS-KBrFA/2024/0083I).