Roswell Park Cancer Institute

490 Background: Patients with hepatocellular carcinoma (HCC) and decompensated cirrhosis (Child-Pugh C) have a poor prognosis, due to underlying liver dysfunction. There is lack of data regarding systemic therapy in patients with HCC and CPC cirrhosis.. Therapeutic decisions in this setting are primarily guided by risk–benefit considerations, as systemic therapy may precipitate further hepatic decompensation. Consequently, most patients receive supportive care. Real-world data regarding systemic treatment outcomes in this population remain scarce. Methods: We utilized de-identified data from TriNetX, a global federated health research network, to identify patients with HCC and CPC cirrhosis using inclusion criteria requiring: bilirubin >2, albumin <3.5, INR >1.7, ascites, and encephalopathy two months prior to diagnosis. We analysed those who initiated systemic therapy with tyrosine kinase inhibitor (TKI) or an immune checkpoint inhibitor (ICI). Overall survival (OS) was assessed using Kaplan–Meier analysis, with group comparisons performed using log-rank tests. Propensity score matching was applied to adjust for age, sex, and comorbidities. Statistical significance was defined as two-sided P ≤ 0.05. Results: A total of 532 patients were included in the analysis. The median age was 63.9 years (range 55–73); 75.40% were male, 57.70% were Non-Hispanic White, 16.16% Black, 9.02% Asian, and 18.04% Hispanic. The Overall Survival (OS) rates for the entire cohort were 36.6% at 1 year, 25.3% at 2 years, 22.3% at 3 years, and 17.5% at 5 years. Among patients who initiated treatment within 3 months of diagnosis, 320 received frontline TKI therapy and 143 received ICI. Among the therapies used, sorafenib was most frequently used (42%), followed by lenvatinib, cabozantinib, regorafenib, atezolizumab plus bevacizumab, pembrolizumab, and durvalumab. After propensity score matching, 136 patients were included in each cohort. No significant difference in OS was observed between the TKI and ICI groups (Table 1). Conclusions: In this real-world cohort of HCC patients with CPC cirrhosis, OS was 36.6% at 1 year, 25.3% at 2 years, 22.3% at 3 years, and 17.5% at 5 years. Frontline TKI therapy showed numerically higher survival than ICI-based regimens, though the difference did not reach statistical significance. These findings highlight the need for prospective studies to better define treatment strategies in this high-risk population. Survival by treatment group. Time TKI OS% ICI OS% HR (95% CI) P Value 1 year 40.2 28 0.74 (0.54–1.03) 0.79 2 years 30.2 24.2 0.78 (0.57–1.06) 0.67 3 years 26.4 24.2 0.79 (0.58–1.08) 0.49

Thyroid diseases are common and highly heritable. We performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer (ThC), benign nodular goiter, Graves’ disease, lymphocytic thyroiditis and primary hypothyroidism. We analyzed genetic association data from ~2.9 million genomes and identified 313 known and 570 new independent loci linked to thyroid diseases. We discovered genetic correlations between ThC, benign nodular goiter and autoimmune thyroid diseases (rg = 0.16–0.97). Telomere maintenance genes contributed to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair and damage response genes were associated with ThC. We propose a paradigm that explains genetic predisposition to benign and malignant thyroid nodules. We found polygenic risk score associations with ThC risk of structural disease recurrence, tumor size, multifocality, lymph node metastases and extranodal extension. Polygenic risk scores identified individuals with aggressive ThC in a biobank, creating an opportunity for genetically informed population screening.

SummaryBackgroundEpidemiological evidence on the influence of ultra-processed foods (UPFs) on breast cancer prognosis is scarce. No study has examined the UPF-mortality association among Black breast cancer survivors.MethodsWe examined the UPF-mortality relationships among Black women diagnosed with primary breast cancer in New Jersey between 2005 and 2019 (n = 1733), who were participants of the Women's Circle of Health Study and Women's Circle of Health Follow-Up Study. Foods and drinks consumed one year before breast cancer diagnosis were assessed during home interviews by validated food-frequency questionnaires. UPFs were classified according to their degree of processing using the standard NOVA classification system. Death outcomes were ascertained through linkage with New Jersey State Cancer Registry files. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for UPF-mortality associations were estimated using Cox and competing risks models, as appropriate.FindingsAfter a median of 9.3 years of follow-up since diagnosis, 394 total deaths (206 breast cancer-related) were identified. In the multivariable-adjusted model, compared to those in the lowest tertile (median = 2.6 servings/day), women in the highest tertile (median = 8.1 servings/day) of UPF intake had statistically significantly higher breast cancer-specific mortality (HR = 1.40, 95% CI = 1.00–1.96, Ptrend = 0.02) and all-cause mortality (HR = 1.36, 95% CI = 1.06–1.74, Ptrend <0.01). Dose-response analyses revealed a J-shaped association of UPF intake with mortality outcome, with lower risk at under 4 servings/day and higher risk at greater consumption (breast cancer mortality Pfor nonlinearity = 0.01). These associations were attenuated after additional adjustment for total energy intake.InterpretationThis large investigation of UPFs and breast cancer prognosis among Black breast cancer survivors suggests that higher consumption of UPFs, which is associated with greater total energy intake, may adversely influence breast cancer prognosis among Black women, a vulnerable population facing the highest risk of breast cancer mortality in the US.FundingThis work was supported by grants from R01CA185623 (Drs. Bandera, Demissie, and Hong), P30CA072720-5929 (Dr. Bandera), R01CA100598 (Dr. Ambrosone), P01CA151135 (Drs Ambrosone, Palmer, and Olshan), R00CA267557 (Dr. Wang) from the National Cancer Institute, and funding from the American Cancer Society RSG-23-1143513-01-CTPS (Dr. Qin) and the Breast Cancer Research Foundation (Dr. Ambrosone). The New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey Department of Health, is funded by the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute under contract 75N91021D00009, the National Program of Cancer Registries (NPCR), Centers for Disease Control and Prevention under grant NU58DP007117 as well as the State of New Jersey and the Rutgers Cancer Institute.

As survival rates for lymphoid malignancies continue to improve, understanding the late effects after treatment, such as secondary myeloid neoplasms (sMN), is increasingly critical for survivorship. This large-scale population-based (SEER-Medicare) study investigated the risk factors and cumulative incidence of sMNs in patients with diagnosis of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and multiple myeloma between 2000 and 2011, with follow-up through 2015. Patients with FL had a continuous increase in the cumulative incidence of sMNs with longer follow-up, whereas incidence of patients with multiple myeloma plateaued after 60 months. Notably, patients with DLBCL diagnosed in more recent years (2004–2007 and 2008–2011) had a higher cumulative sMN incidence compared with those diagnosed earlier (2000–2003). In the Medicare population, older age at diagnosis was associated with significant increase in sMN risk in patients with DLBCL and FL. Chemotherapy exposure or G-CSF exposure significantly increased sMN risk across all three malignancies. Chronic autoimmune conditions increased sMN risk in patients with DLBCL. These findings provide crucial insights into sMN risk factors. Chemotherapy exposure is a recognized risk factor, and comorbidities such as a history of autoimmunity and G-CSF exposures have been identified as additional mediators of sMN risk in our study.Significance:Our study reveals population-level risk factors for sMNs, including novel links to autoimmune disease and G-CSF, in addition to known causes like chemotherapy/radiation. These findings underscore the complex pathogenesis of sMNs and the need for molecular data in prospective studies to guide prevention, detection, and survivorship care.

Fixed-dose subcutaneous (SC) trastuzumab and pertuzumab (HP) (Phesgo®) offers a clinically non-inferior alternative to intravenous (IV) administration for HER2-positive breast cancer, with potential advantages in treatment efficiency. However, real-world evidence on its impact on healthcare workflow and frontline staff remains limited. We conducted a single-center, mixed-methods evaluation comparing SC Phesgo® with conventional IV HP in the perioperative setting. Outcomes included patient treatment time, institutional reimbursement, and the operational burden on nurses and pharmacists, assessed through structured surveys, time-motion observations, and administrative records. Phesgo® reduced active treatment and clinic visit times by up to 96% and 53%, respectively. Cumulative chemotherapy suite time decreased by 332 h over eight months, indicating a potential for resource reallocation. Nurses and pharmacists reported reduced task complexity and improved workflow satisfaction, particularly during monotherapy. .Although combination regimens introduced procedural complexity, professional motivation remained stable. While SC administration is not eligible for chemotherapy-specific reimbursement add-ons in Japan, efficiency gains may partially offset revenue loss. Patient out-of-pocked costs increased slightly in lower-weight individuals but remained modest overall. Phasgo® improves both patient time burden and staff workflow efficiency, supporting more sustainable and patient-centered delivery of HER2-targeted therapy. These findings highlight the broader system-level value of fixed-dose SC regimens in high-volume oncology settings under real-world conditions.

Abstract Glioblastoma (GBM) is the most lethal primary brain tumor in adults presenting with a 95% five-year mortality rate. Due to high relapse rates, GBM remains a major unmet clinical need for new treatment approaches. An innovative approach to target GBM is the administration of chimeric antigen receptor (CAR) T cells to treat relapsed/refractory disease. In this study we identified B7-H3 as an optimal target antigen for CAR T cell therapy of GBM, and developed a novel B7-H3 targeting CAR T cell. These CAR T cells demonstrated robust, antigen-specific cytolysis and cytokine production, while demonstrating low tonic signaling and preservation of a stem/naïve cell phenotype. Using multiple orthotopic xenograft models of GBM we show that a single intravenous administration of B7-H3 targeted CAR T cells confers tumor control, and long-term survival. We identified upregulation of T cell inhibitory ligands PD-L1 and PD-L2 as a mechanism of resistance to CAR T cell therapy. Accordingly, we modified our B7-H3 targeting CAR T cells to secrete a PD-1 blocking scFv downstream of the CAR. Using this armored approach, we further demonstrated that concomitant PD-1 blockade through secretion of a PD-1 blocking scFv by CAR T cells augments the antitumor capabilities of B7-H3-targeting CAR T cells. This was demonstrated through increased infiltration of the adoptively transferred T cells into tumors and improved effector function which conferred durable, long-term remissions in a disease-relevant model of GBM. Together, these data demonstrate B7-H3 targeting CAR T cells armored with concomitant PD-1 blockade are a safe and efficient method for improving the antitumor capacity of B7-H3 targeting CAR T cells in the context of GBM.

&lt;b&gt;Objectives: &lt;/b&gt;This systematic review aimed to evaluate the role of secretory immunoglobulin A (sIgA) and related mucosal immune markers in modulating susceptibility to colonization or infection by antimicrobial-resistant (AMR) bacteria in human and animal models.&lt;br /&gt; &lt;b&gt;Methods: &lt;/b&gt;Studies were included if they assessed mucosal sIgA levels about AMR outcomes, reported original data, and were published in English between 2015 and June 2025. Exclusion criteria included a lack of mucosal immune data or AMR-related endpoints. Databases searched included PubMed, ScienceDirect, and EBSCO (Knowledge and Library Hub), with the last search performed on June 10, 2025. The quality of the included studies was assessed using the checklist for quantitative studies, and data were extracted and synthesized narratively, stratified by immune markers, study design, and mucosal compartment.&lt;br /&gt; &lt;b&gt;Results: &lt;/b&gt;After the systematic search of the databases considered for this review and review of available literature indexed in them, eleven studies that met the inclusion criteria of this study were included in this review.&amp;nbsp; The mucosal sites investigated in most of these studies were gastrointestinal, respiratory, oral, and genitourinary mucosa. Of the eleven (11) studies, four carried out investigations in humans while the remaining seven utilized animal models. All the included studies reported secretory immunoglobulin A (sIgA) level, whereas five of the studies reported other indicators, such as cytokines and IgG, alongside sIgA levels. There was consistency in their results as increased sIgA levels were linked to decreased infection or colonization by AMR pathogens. Moreover, vaccination-based interventional studies showed an increase in sIgA post-vaccination or probiotic treatment.&lt;br /&gt; &lt;b&gt;Conclusion: &lt;/b&gt;Although in this review we included studies with varying methodological approaches as well as studies featuring humans and animal models, the evidence from this review indicates that mucosal sIgA offers protection against antimicrobial-resistant (AMR) bacteria colonization. Therefore, findings from this study suggest that in the quest for addressing AMR that approaches targeting mucosal immunity preventative measures should be explored through standardized trials.