Citations

Background : Metastatic lung carcinoids (MLCs) represent a rare subset of lung cancers with distinct histologic subtypes. Survival outcomes and prognostic factors have not been well-studied in the real-world setting. This study investigates the impact of various treatments, including chemotherapy, hormonal therapy, and no treatment, on the overall survival (OS) of patients with typical and atypical MLC. Methods: Patients with MLC between 2010 and 2020 were included from the National Cancer Database based on histologic codes ICD-O-3 8240/3 and 8249/3. Kaplan–Meier curves and multivariate Cox proportional hazard regression were used to compare OS and evaluate prognostic factors. Results: The median age at diagnosis was 68 and 69 years for atypical and typical MLC, respectively. The 3-year OS for the atypical MLC cohort was 22.11%, and for typical MLC was 41.94% ( P < 0.001). In the atypical MLC cohort, chemotherapy showed a nonsignificant benefit in OS (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.73–1.05; P = 0.21), whereas hormonal therapy was associated with significantly improved OS (HR, 0.72; 95% CI, 0.52–0.98; P =0.04). However, in the typical MLC cohort, chemotherapy was associated with adverse OS (HR, 2.15; 95% CI, 1.85–2.49; P < 0.0001), and hormonal treatment showed better, albeit nonsignificant OS (HR, 0.84; 95% CI, 0.67–1.05; P = 0.13). Conclusion: There is a notable difference in survival outcomes between typical and atypical MLC based on the treatment strategies. While hormonal therapy shows improvement in the OS, the effectiveness of chemotherapy varies depending on the histologic subtype. These findings emphasize the necessity for personalized therapeutic approaches based on the specific characteristics of MLC, ultimately contributing to improved patient outcomes in this challenging oncologic group. Further research is warranted to validate and expand upon these observations.

Abstract Background: Ovarian cancer is the sixth leading cause of cancer deaths among women in the United States. South Asians in the USA, including Asian Indians and Pakistani Americans (AIPA), are a rapidly growing yet under-researched group. This study aims to analyze the clinical features, survival rates, treatment, and outcomes of ovarian cancer among AIPA women in the United States. Methods: Adult women diagnosed with ovarian cancer between 2000 and 2023 within the Surveillance, Epidemiology, and End Results (SEER) registry were identified utilizing ICD codes. The analysis focused on comparing clinical characteristics and outcomes between AIPA and Non-Hispanic White (NHW)women and excluded all women of other races/ethnicities or unknown race/ethnicity. Baseline characteristics, including age at diagnosis, disease stage, and treatment, were compared between AIPA and NHW women utilizing a chi-squared test for categorical variables and a t-test for continuous variables. The 5-year overall survival (OS) was estimated for each race/ethnicity by the Kaplan-Meier method, and the OS was further compared between AIPA and NHW in a cox-proportional hazard regression analysis adjusting for age at diagnosis, grade, histology, TNM stage, surgical debulking, completeness of debulking surgery, and receipt of chemotherapy. Similar comparisons of baseline characteristics and OS were also performed in the subset of women with high-grade serous ovarian cancer (HGSOC). Result: A total of 86, 485 women met the inclusion criteria, of which 1, 179 were AIPA and 85, 306 were NHW. AIPA had a significantly younger median age at diagnosis compared to NHW women in the overall population (57 vs. 65 years, p&lt;0.001) and among 448 AIPA and 29, 677 NHW women with HGSOC (58 vs. 65 years, p&lt;0.001). Approximately two-thirds of women in both groups presented with Stage III or IV ovarian cancer at diagnosis and had a serous subtype of ovarian cancer. Similarly, after the exclusion of unknown grade, high-grade tumors accounted for more than two-thirds (75 vs. 72%) of the ovarian cancer cases in both groups. AIPA were more likely to undergo debulking surgery (85 vs. 80%, p&lt;0.001) and receive chemotherapy (77 vs. 72%, p&lt;0.001) compared to NHW women. The unadjusted 5-year OS for AIPA and NHW women were 56% vs. 43% in the overall population, and 53% vs. 41% among women with HGSOC, respectively. In multivariate analysis of the entire study population, AIPA women had a significantly better OS than NHW women (HR: 0.86, 95%CI: 0.79 - 0.94, p&lt;0.001). Among women with HGSOC, a similar trend of better OS was noted in multivariate analysis among AIPA women compared to NHW (HR: 0.88, 95%CI: 0.77 - 1.01, p=0.07), although this did not reach statistical significance. Conclusion: The younger age at diagnosis, along with a generally better prognosis, among AIPA women compared to NHW women, suggests a possible enrichment of DNA-repair gene alterations among AIPA women. Citation Format: Aditi Karki, Sumeet Kumar Yadav, Muhammad Rafiqul Islam, Raja Pramanik, Ramila Shilpakar Dangol, Zeba Aziz, Sandhya Pruthi, Maryam Shahi, Jamie N. Bakkum-Gamez, Scott H. Kaufmann, Fergus J. Couch, Siddhartha Yadav. Clinical characteristics and survival outcomes of ovarian cancer among South Asian women in United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7118.

Abstract Introduction: Multiple myeloma (MM) is a B-cell-derived malignancy associated with immune dysregulation. Anti-CD38 monoclonal antibodies (mAbs) therapies have shown improved outcomes in patients with MM. Silbermann et al. showed that anti-CD38 mAb-containing therapies lead to profound hypogammaglobulinemia and reduction in Ig gene repertoire. The effect of modern therapies such as CAR-T and bispecific antibodies (BsAbs) on B-cell repertoire has not been well described. In this study, we sought to investigate the effect of these therapies on B-cell repertoire in patients with MM. Methods: This is a single-institution retrospective observational study evaluating MM patients treated with anti-BCMA CAR-T and BsAbs. Baseline characteristics, laboratory data, treatment history, were extracted from medical records. Total unique sequences (TUS) and total sequences of IgH, IgK, and IgL were identified and quantified using clonoSEQ. Patients were classified in two groups: CAR-T and BsAbs. The primary objectives were (1) characterize changes in TUS and total sequences within IgH, IgK, and IgL before and after treatment, and (2) examine how the sequences evolve over time following CAR-T. Results: 76 MM patients received CAR-T or BsAbs. Among those, 22 CAR-T and 5 BsAbs patients had pre- and post-treatment sequences available. Median age at initiation of treatment was 66 years in the CAR-T group (42-81 y) and 65 years in the BsAbs group (48-71 y). Based on mSMART v3 criteria, 72% of CAR-T and 60% of BsAbs recipients were classified as high-risk. Median number of prior lines of therapy was 5 (2-8) in the CAR-T group and 6 (5-13) in the BsAbs group.CAR-T recipients were classified into early (&lt;40 days) and late (&gt;40 days), based on when the post-CAR-T treatment clonoSEQ assay was performed. Changes in TUS and total sequences of IgH, IgK, and IgL were calculated, and the averages were assessed independently. The mean early and late change in total unique IgH sequences were (-75, 586 and 131, 038, p=0.052), unique IgK (-57, 797 and 52, 586, p=0.020), and unique IgL (-22, 354 and 25, 056, p=0.011). A subgroup of 8 patients with sequential MRD reports post-CAR-T therapy were identified, six patients showed improvement in B-cell sequence dynamics and two patients showed a decrease over time. For patients who received BsAbs, results indicated a similar pattern, with an early decrease in B-cell repertoires, characterized by reductions in sequence diversity and quantity. Conclusions: Our analysis of B-cell repertoires following CAR-T revealed changes before and after treatment. Patients receiving CAR-T therapy showed a decline in the number of TUS and total sequences of IgH, IgK, and IgL, likely due to the lymphodepletion regimen, followed by a gradual restoration reflecting immune recovery. Longer follow-up and a larger cohort will be necessary to assess the implications of these B-cell repertoire changes on patient outcomes. Citation Format: Feba Miriam Jacob, Rodolfo Garza-Morales, Joseph G Hentz, Alex Wonnaparhown, Julia E. Wiedmeier-Nutor, Mariano Arribas, Gabriela Alatorre, Sharene Best, Jayden Poulignot, Udit Yadav, Saurabh Chhabra, P. Leif Bergsagel, Rafael Fonseca, Talal Hilal. Dynamics of B-cell repertoires following CAR-T and bispecific antibody therapy in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4537.

Abstract Studies have identified genetic and epidemiologic factors associated with mammographic density (MD) phenotypes. However, MD-associated genetic variants only account for a small proportion of the total estimated heritability. Interrogating interactions between genetic and epidemiologic factors could potentially identify additional MD-associated loci, expand our understanding of the genetic basis of MD phenotypes, and clarify how epidemiologic factors modulate relationships between genetic variants and MD. We conducted six separate genome-wide, gene–environment (GxE) interaction analyses, applying 2 degrees of freedom (df) and 1df interaction tests, for each of three MD phenotypes (percent density, dense area (DA), and nondense area (NDA)). The six epidemiologic factors considered were height, ever parous, parity, ever menopausal hormone therapy, ever breastfeeding, and months of breastfeeding. We included European ancestry participants from multiple studies within the Markers of Density consortium and the Breast Cancer Association Consortium (n = 4895-16 218 depending on specific analyses). We identified 11 loci with genome-wide significant (P &lt; 5 × 10−8) interaction tests including two novel common genetic signals interacting with parity (8p21.2) and ever breastfeeding (19p13.2) for NDA. Our results suggest that epidemiologic risk factors might influence relationships between common genetic variants and MD phenotypes at particular genomic loci.

Abstract Purpose: Germline alterations in homologous recombination repair (gHRR) genes affect the pathogenesis, treatment options, and survival of patients with cancer. However, distinct gHRR gene alterations may differentially affect treatment response and oncogenic signaling. In this study, we interrogated genomic and transcriptomic data and assessed clinical outcomes of patients with gHRR mutations across four BRCA-associated cancers (breast, ovarian, pancreatic, and prostate cancers) to identify therapeutic vulnerabilities. Experimental Design: We assessed 24,309 patients undergoing matched tumor/normal next-generation DNA and RNA sequencing. Annotated gHRR gene variants [germline BRCA1, germline BRCA2, germline PALB2, germline ATM (gATM), and germline CHEK2] were analyzed. HRs were used to assess survival outcomes comparing germline versus sporadic groups. Somatic alterations and their frequencies were compared across gHRR-altered groups. Differential gene expression and gene set enrichment analysis were used to compare transcriptomic profiles. Results: Somatic TP53 mutations were depleted in gATM carriers (P &lt; 0.05) across all four BRCA-associated cancers by up to 2.5-fold. Tumors with germline BRCA1/2 mutations were associated with improved survival in patients with ovarian cancer and had consistent enrichment of TP53 mutations in all four cancers. gATM mutations displayed elevated p53 transcriptional activity in all four cancers, with significance reached in breast and prostate cancers (P &lt; 0.01). In breast, ovarian, and prostate cancers, gATM tumors demonstrated significantly increased inflammatory pathways (P &lt; 0.001). Finally, using gene dependency data, we found that cell lines that were highly dependent on ATM were co-dependent on canonical p53 function. Conclusions: gATM-associated cancers seem to require intact p53 activity and this synthetic essentiality may be used to guide targeted therapies that perturb canonical TP53 function.

Background and aims: Traditionally, low molecular weight heparin, such as dalteparin, has been the first-line treatment for cancer-associated venous thromboembolism (VTE). However, recent studies suggest that rivaroxaban, a direct oral anticoagulant, may offer comparable efficacy with the convenience of oral administration. This systematic review and meta-analysis aim to evaluate and compare the efficacy and safety of rivaroxaban versus dalteparin in managing cancer-associated VTE, focusing on recurrence rates, bleeding events, and patient adherence. Methods: This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines, systematically retrieving data from PubMed and Cochrane databases using structured search terms related to cancer, VTE, and anticoagulation. Data on recurrent VTE, major bleeding, and patient outcomes were extracted. Statistical analyses were performed using a random-effects model to account for heterogeneity. Results: Nine studies were analyzed, encompassing a range of study designs across multiple countries. The findings show no significant difference in major bleeding risk between rivaroxaban and dalteparin (risk ratio: 0.91, P = 0.69), nor in bleeding-related mortality (odds ratio [OR]: 4.00, P = 0.36). Rivaroxaban was associated with a significant reduction in deep vein thrombosis (DVT) recurrence (OR: 0.75, P = 0.04) and a marginally nonsignificant reduction in pulmonary embolism recurrence (OR: 0.73, P = 0.05). Nonsignificant bleeding events were slightly higher with rivaroxaban but did not reach statistical significance. Conclusion: Rivaroxaban presents a viable alternative to dalteparin for treating cancer-associated VTE, showing comparable safety regarding major bleeding and potential efficacy in reducing DVT recurrence. This study supports the potential for more standardized guidelines that include rivaroxaban as a feasible option in cancer-associated VTE management.

INTRODUCTION: Opioids are used to treat pain in chronic pancreatitis (CP), but little is known about current use patterns. The aim of this study was to characterize the utilization of opioids and associations with clinical characteristics in adult patients with CP. METHODS: This cross-sectional analysis used baseline data from participants with definite CP enrolled in a cohort study in the United States (PROspective Evaluation of CP for EpidEmiologic and Translational StuDies). Data on demographics, pain medication use, healthcare utilization, disability, and pain patterns were systematically collected in case report forms while quality of life was assessed with patient-reported outcome instruments. Opioid use was classified according to strength (weak or strong) and frequency (scheduled or as-needed). RESULTS: A total of 681 participants (n = 364, 53% male) were included: 299 (44%) were current opioid users (22% only weak opioids and 22% at least 1 strong opioid). Increasing frequency and severity of pain was associated with increase of weak, strong, as-needed, or scheduled opioids. Neuromodulators were used by ∼40% of participants; increasing use was associated with increasing frequency and severity of pain. On multivariate analysis, independent predictors associated with strength and frequency of current opioid use were pain patterns (odds ratios [ORs] 1.84–8.32 and ORs 1.92–8.52, respectively, P < 0.001) and prior celiac plexus block (OR 3.54, 95% confidence intervals 1.82–6.87 and OR 3.42, 95% confidence intervals 1.76–6.64, respectively). Participants using opioids had higher prevalence of disability, healthcare utilization, and poorer quality of life. DISCUSSION: Opioid use in CP is common and associated with increased pain severity and constancy. These data provide foundational estimates for future trials that can elucidate the complex interactions between patient factors, pain, and interventions.