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Lisocabtagene maraleucel (liso-cel) as first-line (1L) therapy for transplant-ineligible patients (pt) with primary central nervous system lymphoma (PCNSL): The CAROLYN study.
TPS7097 Background: Treatment of PCNSL is based on high-dose methotrexate (HD-MTX) induction chemotherapy, followed by consolidative autologous stem cell transplantation (ASCT) in eligible pts. Those deemed transplant ineligible have a high risk of relapse and are a population with a significant unmet therapeutic need. Liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, demonstrated promising results in secondary CNS lymphoma. In a phase 2 study (NCT03484702), 4 of 5 pts with PCNSL treated with liso-cel after failure of 1L high-dose chemotherapy and ASCT achieved a CR. Here, we report the study design of the CAROLYN study (NCT07015242; currently enrolling), which is evaluating efficacy and safety of liso-cel as 1L therapy in transplant-ineligible pts with PCNSL. Methods: This open-label, single-arm, multicenter, phase 2 study will enroll approximately 65 pts. The primary endpoint is investigator-determined 12-month PFS rate (from infusion date). Secondary endpoints include additional efficacy assessments (PFS, event-free survival, and OS from enrollment; CR rate, ORR, and duration of response), safety (AEs, serious AEs, and AEs of special interest), and health-related quality of life. Key inclusion criteria are newly diagnosed PCNSL confirmed by local pathology, receipt of ≥ 2 cycles of standard-of-care regimens, transplant ineligibility (defined by investigator assessment and either age ≥ 65 years or hematopoietic stem cell transplantation-specific comorbidity index score ≥ 3), MTX-sensitive disease (CR or PR), and ECOG PS ≤ 2. Key exclusion criteria include diagnosis of secondary CNS lymphoma, primary intraocular lymphoma, primary vitreoretinal lymphoma, and isolated cerebrospinal fluid involvement. Enrolled pts can receive optional holding therapy with a HD-MTX–based regimen while awaiting leukapheresis. After leukapheresis, bridging therapy with a HD-MTX–based regimen is permitted during liso-cel manufacturing. Before liso-cel infusion, pts receive lymphodepleting chemotherapy consisting of fludarabine (30 mg/m 2 /day for 3 days) and cyclophosphamide (300 mg/m 2 /day for 3 days). Pts then receive a single infusion of liso-cel at a target dose of 100 × 10 6 CAR + T cells. After infusion, pts remain in the treatment period for 90 days and then transition to follow-up for 2 years from enrollment. The total study duration is expected to be 3 years; pts who receive liso-cel can enroll in a separate 15-year long-term follow-up (NCT03435796). Clinical trial information: NCT07015242 .
Precision risk stratification for lung cancer in COPD: Evidence from the All of Us Program.
10537 Background: Chronic obstructive pulmonary disease (COPD) is a well-established independent risk factor for lung cancer, yet determinants of cancer susceptibility within this high-risk population remain incompletely characterized. Identifying clinical and genomic predictors is essential to improve risk stratification, early detection, and precision prevention strategies. Methods: We conducted an age-matched case–control study using de-identified data from the All of Us Research Program to evaluate sociodemographic characteristics, comorbidities, and genetic variants associated with lung cancer risk among adults with COPD. Baseline characteristics were summarized using descriptive statistics. Multivariable logistic regression was used to estimate adjusted odds ratios (AORs) controlling for relevant confounders. Genome-wide association studies (GWAS) were performed with rigorous quality control, population stratification adjustment, and correction for multiple testing. Results: Among 633,540 participants, 26,570 (4.2%) had COPD, including 2,044 (7.7%) with lung cancer. The mean age was 67.5 ± 11.4 years; 43.4% were male. In multivariable analysis, Asian ancestry was associated with increased lung cancer risk (AOR 2.25, 95% CI 1.55–3.26). Age 66–95 years conferred a 29% higher risk, and family history of lung cancer increased risk by 34% (95% CI 1.15–1.57). Hypothyroidism (AOR 1.58, 95% CI 1.27–1.97) and hyperlipidemia (AOR 1.32, 95% CI 1.04–1.68) were independently associated with lung cancer. GWAS identified 19 variants significantly associated with lung cancer risk, including rs539223166, rs551676206, rs922466204, rs144626313, rs147989022, and rs74502961. Conclusions: Distinct clinical and genetic factors contribute to lung cancer susceptibility among individuals with COPD. Integrating these determinants may enhance risk prediction and inform targeted surveillance strategies.
Alzheimer’s biomarkers in oncology: The impact of cancer treatment on neurodegenerative diagnostic disparities across populations.
e14048 Background: The intersection of oncology and neurodegenerative disorders has illuminated complex interactions existing among cancer treatments, cognitive decline, and Alzheimer's disease (AD) biomarkers. Even under the circumstance that we see differences in levels of AD biomarkers across ethnoracial groups, in addition to the cognitive impacts of cancer related cognitive decline (CRCD), cancer survivors may require consideration for an individualized and personalized approach to diagnostics. This systematic review aims to synthesize evidence around the impacts of cancer treatments on AD biomarker levels in cognitive outcomes within a heterogeneous population. Methods: A systematic review was conducted, following guidance from PRISMA. The search of the following databases were completed: PubMed, EMBASE, Scopus, and Cochrane, using literature published from the year 2010 ending in 2024. The studies included analyzed cognitive outcomes; AD biomarker levels (that included amyloid, tau, and APOE genotype); and ethnoracial differences in patients with cancer. We extracted data related to the cancer treatment, biomarker levels, the testing for cognitive purposes, and neuropathological outcomes. Ethnoracial differences were analyzed in consideration to the following minority groups: African Americans, Mexican American, and non-Hispanic White. Results: A total of 25 studies and 3,809 participants were included. Compared to participants without cancers, individuals diagnosed who were cancer survivors showed lower odds of an AD diagnosis, and less burden of AD pathology in the brain subsequently. Individuals who received chemotherapy had a lower chance of dementia than cancer individuals who did not receive treatments. Nonetheless, cancer related neurologic pathology, including cerebral amyloid angiopathy, neuritic plaques, and neurofibrillary tangles, was lower in survivors, making AD diagnostics, especially with biomarkers more difficult claiming them to be biased towards AD diagnosis. Ethnoracial characteristics were noted, as African American samples showed less burden of AD biomarkers raising the need for population specific diagnostic criteria. Conclusions: Our review highlights significant disparities in AD biomarkers and cognitive outcomes among cancer survivors, particularly across ethnoracial lines. Cancer treatments appear to modulate AD pathology, suggesting the need for ethnoracial-specific biomarker validation and diagnostic approaches. This underscores the importance of precision medicine in addressing disparities in neurodegenerative diagnostics, particularly for populations with a history of cancer.
Nanoconfinement Enabled High‐Efficiency and Long‐Lifetime Multicolor Afterglow Hydrogels for Advanced Spatiotemporal Encryption and Pathogen Eradication
ABSTRACT Multicolor organic afterglow hydrogels that simultaneously possess efficient exciton harvesting, ultralong lifetimes and large deformations are still rare. Here, a nano‐restriction engineered strategy that embeds a rigid and chromatically diverse hydrogen bond supramolecular framework into hydrogel networks is presented. The confined microenvironment of the supramolecular framework suppresses non‐radiative quenching to prolong triplet lifetimes and acts as stress‐dissipating nodes to reinforce the polymer matrix. The synthesized hydrogels exhibit tunable afterglow emissions from deep blue to orange–red, lifetimes up to 2535 ms, and quantum yields above 29.4%, while retaining a compressive strength of 7.7 MPa and fracture strain near 1400%, with excellent stability under repeated cycling. Programmable color and decay dynamics of afterglow hydrogels enable spatiotemporally resolved encryption. Moreover, the long‐lived triplet excitons efficiently sensitize singlet oxygen, delivering >99.9% antibacterial efficacy to accelerate infected wound healing. This approach provides a general route to develop multifunctional afterglow soft materials that couple high exciton utilization and ultralong lifetime with mechanical robustness.
APE1‐Triggered Inhalable Microsphere (ATIM) for In Situ Non‐Small Cell Lung Cancer Theranostics
ABSTRACT Distinguishing benign from malignant pulmonary nodules remains a major clinical challenge, where misdiagnosis may lead to either delayed cancer treatment or unnecessary invasive procedures. Here, we report apurinic/apyrimidinic endonuclease 1 (APE1)‐triggered inhalable microsphere (ATIM) for non‐small cell lung cancer (NSCLC) theranostics by leveraging inhalation delivery and homotypic targeting to accelerate the local enrichment of DNA tetrahedrons (TDNs) in pulmonary tumors, which enables in situ NSCLC theranostics. Upon intracellular recognition of the APE1, entropy‐driven catalytic circuits are activated, triggering nanoparticle aggregation to amplify fluorescence for real‐time tumor imaging and releasing miR‐126‐3p to induce tumor cell apoptosis by suppressing ADAM9. In a mouse orthotopic NSCLC model, the tumor‐bearing group showed a fluorescent intensity 1.67‐fold higher than the healthy group, and the pulmonary accumulation of the ATIM system via inhalation was 3.12‐fold higher than that via intravenous injection, while ATIM therapy significantly reduced the tumor burden to a relative area of 45.3 ± 1.6%. Our results demonstrate that ATIM achieves accurate discrimination between benign and malignant pulmonary nodules while effectively inducing apoptosis in tumor cells. This theranostic system offers a promising dual‐functional platform for precision diagnosis and targeted therapy in early‐stage NSCLC.
Real-world utilization of a patient-centric symptom management guide for metastatic breast cancer.
e23403 Background: Metastatic breast cancer (MBC) and its treatments are associated with significant symptom burden that can negatively impact quality of life (QoL), adherence to therapies, and patient-provider communication. Individuals with MBC can be inundated with complex information during clinical encounters, and oral information retention may be limited. Although evidence-based symptom management strategies exist, many educational resources are not designed in an accessible, patient-centered format, limiting real-world use. Co-created tools may improve usability and adoption, yet evidence of sustained implementation in practice remains limited. Methods: An evidence-based symptom management MBC Guide that was co-developed with patients and healthcare providers endorsed by AONN+ has been implemented in clinical practice. Post-implementation evaluation included analysis of Viver’s ordering and reordering data, along with provider survey responses assessing utilization, satisfaction, and perceived impact. Results: Real-world data demonstrate sustained adoption in clinical practice, with > 384 total orders and > 30 reorders over the past 6 months, indicating continued use in clinical workflows. Providers reported high endorsement, with 91% reporting they were extremely or very likely to recommend the guide to other HCPs on a 10-point Likert scale. Ease of patient understanding was also rated highly, with 92% of providers stating it was easy or very easy for patients to read and understand. Providers identified the greatest impact on their practice as increasing patients’ ability to manage symptoms (44%), enhancing communication and shared decision-making (38%), and improving patient experience and QoL (18%). Additionally, 75% of providers expressed interest in a Spanish-language version. Conclusions: Sustained ordering, reordering behavior, and strong provider endorsement help to validate the patient-centric, co-created design of this MBC symptom management Guide. Post-implementation data demonstrate real-world feasibility, usability, and perceived impact on symptom self-management, provider-patient communication, and patient experience, supporting co-creation as an effective strategy for developing scalable, practice-ready educational tools. Ongoing efforts include translation into Spanish to expand reach and equity.
Clinico-genomic landscape of Indian gallbladder cancer: Actionable alterations and opportunities for precision therapy.
e16231 Background: Gallbladder carcinomas (GBC) are the predominant biliary tract malignancies with marked geographic variation and a female-biased, middle-aged patient population. Most patients present with advanced disease, and adjuvant chemotherapy offers limited survival benefit. Mutation profiling can reveal actionable alterations and immunogenomic contexts to guide precision therapeutics and potential trial design. Methods: This study analyzed 115 FFPE-tumor samples from patients undergoing treatment for GBC across multiple hospitals in India, who had opted to undergo molecular genetic testing for somatic variants with 4baseCare’s comprehensive gene panels. Results: The cohort was predominantly female (70.3%), particularly 50 and older (73.07%), and largely derived (85.5%) from high-incidence regions of India. Nearly all patients (98.5%) presented with stage IV disease; adenocarcinoma was the most predominant histological type (61%) Among the IHC markers tested, CK7 and CK19 were frequently positive in evaluated samples, while CK20 and PD-L1 were largely negative. Recurrent genomic alterations included ERBB2 (10.7%), BRCA2 (6.8%), SMAD4 (6.8%), CDKN2A (3.9%), and MDM2 (3.9%), with copy-number amplifications involving ERBB2 and MDM2. Most commonly affected pathways were cell-cycle regulation (37%), RTK signaling (16%), PI3K/AKT/mTOR signaling (11%), DNA damage repair (7%), and chromatin remodeling/DNA methylation (6%). TMB was predominantly low, with only 4.8% demonstrating high TMB. 93.1% samples in a subset were microsatellite marker stable. Overall, 4.76% of samples harbored alterations potentially targetable with FDA-approved therapies. Conclusions: The data reveal a predominance of mutations in RTK/cell-cycle–DNA damage pathways indicating that GBC patients may benefit from targeted therapy. Although actionable targets were identified in a minority of cases, CGP delineates clinically relevant subsets that may benefit from targeted agents, pathway-directed therapies, or immunotherapy where biomarkers align. Routine integration of CGP in advanced GBC may refine treatment selection, improve trial stratification, and support biomarker-driven precision oncology approaches in this high-incidence population.
Comparative transcriptomic analysis of chemotherapy-naive and post-chemotherapy germ cell tumors.
5026 Background: Cisplatin-based chemotherapy is highly effective in testicular germ cell tumors (GCTs); however, the presence of viable tumor after first-line chemotherapy is associated with chemoresistance and poor clinical outcome. The transcriptional programs distinguishing chemotherapy-naïve and post-chemotherapy viable GCTs remain incompletely characterized. Methods: Tumor samples from 50 GCT patients treated between 2010 and 2022 were analyzed, including 30 chemotherapy-naïve tumors and 20 post-chemotherapy viable GCTs resected from the retroperitoneum. Five normal testicular tissue samples served as controls. Formalin-fixed paraffin-embedded samples were profiled using the HTG EdgeSeq Oncology Biomarker Panel. Differential gene expression analysis was performed using DESeq2, adjusted for histology, with significance defined as adjusted p-value < 0.1 and |log2 fold change| > 1. Functional enrichment analysis was conducted to identify deregulated biological pathways. Results: Compared with normal testicular tissue, chemotherapy-naïve GCTs and post-chemotherapy viable GCTs exhibited 1,010 and 720 differentially expressed genes, respectively. Direct comparison between chemotherapy-naïve and post-chemotherapy tumors identified 424 differentially expressed genes. Post-chemotherapy viable GCTs demonstrated marked downregulation of genes associated with pluripotency and embryonal stem cell identity, including POU5F1 , UTF1 , DPPA4 , and PRDM14 . In contrast, post-chemotherapy tumors showed upregulation of immediate early stress response genes, inflammatory and cytokine signaling pathways, EGFR-related growth factor signaling, and metabolic stress adaptation. Conclusions: Post-chemotherapy viable GCTs are characterized by loss of pluripotent transcriptional programs and acquisition of stress-responsive, inflammatory, and adaptive signaling pathways. These transcriptional changes provide insight into the biology of chemotherapy resistance in GCTs and may have prognostic and therapeutic implications.
Targeted combination therapies for untreated chronic lymphocytic leukemia: A network meta-analysis of randomized trials.
7048 Background: Treatment options for previously untreated chronic lymphocytic leukemia (CLL) have expanded to include both fixed-duration venetoclax-based combinations and continuous Bruton tyrosine kinase (BTK) inhibitor therapy. While both approaches improve outcomes compared with chemoimmunotherapy, their relative benefits and risks have not been well defined. We performed a network meta-analysis to compare the efficacy and safety of these frontline targeted strategies. Methods: We searched MEDLINE, Embase, PubMed, the Cochrane Library, Web of Science, and major oncology conference proceedings from inception through November 2025. Phase II–III randomized trials enrolling treatment-naïve adults with CLL and evaluating venetoclax-based combinations or continuous BTK inhibitor–based regimens were included. A frequentist random-effects network meta-analysis was conducted. Treatment effects were summarized using hazard ratios (HRs) for progression-free survival (PFS) and risk ratios (RRs) for grade ≥3 adverse events. Results: Eight randomized trials including 3,056 patients and five treatment regimens were analyzed. All targeted therapy–based regimens significantly improved PFS compared with chlorambucil plus obinutuzumab. The greatest PFS benefit was observed with ibrutinib plus obinutuzumab (HR 0.41; 95% CI, 0.29–0.59), followed by venetoclax plus ibrutinib and venetoclax plus obinutuzumab. Acalabrutinib plus obinutuzumab also significantly reduced the risk of progression (HR 0.52; 95% CI, 0.41–0.67). No significant inconsistency was detected across the treatment network. Safety outcomes varied by regimen, reflecting differences in treatment duration and mechanism of action. Conclusions: In previously untreated CLL, fixed-duration venetoclax-based combinations achieve PFS outcomes comparable to continuous BTK inhibitor–based therapy, with distinct safety and treatment exposure profiles. These findings support personalized frontline treatment selection based on patient comorbidities, tolerability, and preference for time-limited therapy.
A structured patient advocacy–led communication model to improve awareness, trust, and access to oncology clinical trials in Brazil.
e13505 Background: In low- and middle-income countries (LMICs) like Brazil, participation in oncology clinical trials is hindered by limited Portuguese-language information, low health literacy, and historical mistrust. Patient advocacy organizations are vital bridges between patients, investigators, and sponsors. This work evaluates a national advocacy-led program designed to improve awareness and informed access to research through patient-centered communication. Methods: "Walking with Confidence" ( Caminhando com Confiança ) is a nationwide program by Instituto Projeto CURA, grounded in Good Clinical Practice and Brazilian regulations. The multi-channel initiative includes: Educational Materials: Paper brochures and curated digital content reviewed by CURA’s Scientific and Patient Committees for lay audiences. CURA Talks: Thematic educational events held alongside oncology congresses. Health Literacy Initiatives: Digital content and forums to clarify scientific concepts. CURA Meetings: Multi-stakeholder forums involving investigators, research centers, and health system leaders. Performance was prospectively monitored throughout 2025 using digital engagement and event-based metrics. Results: In 2025, the program achieved the following milestones: Digital Outreach: Published > 250 posts/stories and > 30 in-depth scientific reviews. The program reached 365,000+ individuals on Instagram (12,000+ interactions) and generated 535,000+ LinkedIn impressions. Direct Engagement: Conducted 4 CURA Talks and 1 CURA Meeting, averaging 100 participants per event (patients, caregivers, and professionals). Web & Email: The institutional website saw ~7,100 visits. Newsletters reached 2,961 subscribers, resulting in 8,647 opens and 7,287 clicks Compliance: All activities were non-promotional and maintained full ethical and regulatory compliance. Conclusions: The "Walking with Confidence" program offers a scalable, ethical model for enhancing the clinical research ecosystem in Brazil. By fostering patient autonomy and professional literacy, the program promotes inclusive trial participation and accelerates the local development of oncology innovations.
Real-world outcomes from 3D-PREDICT glioma chemosensitivity testing of primary CNS tumors.
2060 Background: 3D-Predict Glioma is an ex vivo chemosensitivity assay that predicts response to 12 systemic agents using patient-derived 3D cell cultures. Prospective studies showed predictive accuracy, but real-world data linking assay-guided therapy selection to clinical outcomes remain limited. We analyzed outcomes at a tertiary cancer center. Methods: This retrospective–prospective chart review included patients with primary CNS tumors who underwent chemosensitivity testing at an urban cancer center since 3/2023. Demographics, tumor characteristics, assay results for the 12-drug panel, treatment selection, and clinical outcomes were abstracted. Drug response was categorized as response, moderate response, or no response. Survival analyses were performed using the Kaplan–Meier method. Results: Among the 96 patients, ECOG was 0 in 21 (22.1%), 1 in 37 (38.9%), 2 in 26 (27.4%), and 3 in 11 (11.6%). Insurance coverage included private (69, 71.9%), Medicaid/Medicare (14, 14.5%), Private plus Medicaid/Medicare (12, 12.5%), or self-pay (1, 1.0%). At the time of analysis, 85 patients (88.5%) were alive. Median age was 64 years (range 25–86; IQR 56–71), and 53 (55.2%) were female. Most were diagnosed with adult-type diffuse glioma (92, 95.8%), including 84 (87.5%) glioblastoma. Chemosensitivity testing failed in 10 (10.4%) cases due to insufficient tissue quantity or quality control. All remaining cases yielded 1 or more drugs with assay-predicted responses. Response rates for each drug are detailed in the Table. Mean time to results was 8.8 days (range 5–15). Assay-guided therapy was selected in 59.5%, predominantly temozolomide. The remaining patients received other agents on trial, standard-of-care physician's choice, no further therapy, or transferred care. Key endpoints analyzed included progression-free survival (PFS), PFS at 6 months, overall survival (OS), OS at 12 months, and time-to-progression (TTP) ratio. Conclusions: In a real-world CNS tumor cohort, 3D-Predict Glioma identified potentially active agents and influenced treatment selection in more than half of patients. Our series suggests that chemosensitivity-guided therapy is feasible in routine neuro-oncology practice. Response rates by drug. Drug Newly Diagnosed Progression Pseudoprogression All Abemaciclib 17 (37.8) 10 (47.6) 2 (100.0) 29 (42.6) Carboplatin 30 (60.0) 11 (50.0) 2 (100.0) 43 (58.1) Dabrafenib 4 (8.0) 4 (17.4) 0 (0.0) 8 (10.7) Etoposide 13 (25.5) 5 (21.7) 0 (0.0) 18 (23.7) Everolimus 44 (100.0) 22 (100.0) 2 (100.0) 68 (100.0) Irinotecan 23 (45.1) 9 (34.6) 0 (0.0) 32 (40.0) Lomustine 2 (3.9) 1 (4.3) 0 (0.0) 3 (3.9) Osimertinib 8 (17.4) 5 (23.8) 0 (0.0) 13 (18.8) Procarbazine 50 (100.0) 23 (95.8) 2 (100.0) 75 (98.7) Rucaparib 43 (86.0) 17 (73.9) 2 (100.0) 62 (82.7) Temozolomide 20 (39.2) 10 (40.0) 2 (66.7) 32 (40.5) Trametinib 20 (44.4) 6 (28.6) 0 (0.0) 26 (38.2) Denominators defined by available results per drug; N (%).
Leveraging real-world genomic data to characterize immunotherapy response in cancers with germline <i>CHEK2</i> cancer risk variants.
e22643 Background: CHK2 is a DNA damage response (DDR) protein critical for maintaining genomic stability. Germline CHEK2 variants occur at 1-2% in the general population and confer elevated risk for multiple cancers. Loss-of-function mutations in DDR genes can sensitize tumors to immunotherapy through effects on tumor immunogenicity and immune signaling. We examined the relationship between germline CHEK2 variants and immune biomarkers across cancer types. Methods: We used the Tempus Lens Platform (Tempus AI, Inc., Chicago, IL) to query the de-identified, multimodal Tempus database for patients (pts) with tumor-normal matched samples, Tempus xT (DNA, 648 genes) sequencing, at least 30% tumor purity, and any cancer diagnosis. Pts with known mismatch repair (MMR) deficiency or pathogenic/likely pathogenic germline variants (PGVs) in Tempus germline reportable genes other than CHEK2 were excluded to minimize confounding effects on immunogenicity. PD-L1 expression was assessed by IHC. Tumor immune microenvironment composition was evaluated using quanTIseq. Pt characteristics were compared using Chi-squared, Fisher’s exact, or Wilcoxon rank sum tests, as appropriate. Time-to-event analyses were restricted to pts with non-small cell lung cancer (NSCLC), with the index date defined as initiation of first-line (1L) treatment. Risk set adjusted real-world time to next treatment (rwTTNT) and real-world overall survival (rwOS) were analyzed by Kaplan-Meier and Cox proportional hazards models. Results: The evaluable cohort included 89,326 pts (median age at diagnosis 65; 50% female) of whom 1,323 (1.5%) harbored CHEK2 PGVs. Pts with CHEK2 PGVs were more likely to self-identify as White (94% vs. 79%; p < 0.001) but were similar in age and sex distribution. No clinically significant differences in tumor mutational burden (TMB), PD-L1 expression, microsatellite instability, or immune cell infiltration were observed between pts with or without CHEK2 PGVs. ERBB2 amplification was enriched in pts with CHEK2 PGVs, and TP53 and RB1 somatic variants were enriched in pts without CHEK2 PGVs. Treatment response data were available for 3,567 (rwTTNT) and 3,588 (rwOS) pts with NSCLC, including 39 pts with CHEK2 PGVs. In univariable analyses, pts with CHEK2 PGVs had modestly prolonged rwTTNT (median not reached vs. 12.95 months; HR = 0.52; p = 0.039) and rwOS (median 32.35 vs. 18.64 months; HR = 0.78; p = 0.26). In multivariable analyses, including 1L ICI, PD-L1, and TMB, this trend continued for both rwTTNT and rwOS. However, no significant interaction terms were observed. Conclusions: CHEK2 PGVs were not associated with known biomarkers of immunotherapy response. The observed prolonged TTNT in pts with NSCLC and CHEK2 PGVs highlights the need for further studies to clarify how tumors arising from CHEK2 PGVs differ biologically and prognostically from those with intact CHK2 function.
Safety and efficacy of asciminib in veterans with chronic myeloid leukemia.
6591 Background: Asciminib was approved for use in previously treated patients with chronic myeloid leukemia (CML) in 2021. It employs a novel allosteric mechanism that can overcome resistance and intolerance to conventional tyrosine kinase inhibitors (TKIs). We assessed the efficacy and clinical outcomes of asciminib in Veterans with CML following failure of first- and second-generation TKIs. Methods: Utilizing the VA Informatics and Computing Infrastructure (VINCI), we reviewed all 116 Veterans nationwide with a diagnosis of CML who were treated with asciminib prior to August 2025. Demographic and clinical data collected included age at diagnosis, gender, race, prior CML treatments, and BCR-ABL transcript levels at treatment initiation and at 3 and 6 months. Safety outcomes included the development of thrombocytopenia and neutropenia. Mortality data were collected when applicable. Since more than half of the patients were still alive at the time of chart abstraction, median survival could not be reliably estimated (median 3.4 years, lower limit 2.8 years, upper limit NA). We therefore report the restricted mean survival time (RMST). Results: 110 Veterans were included in the analysis after excluding 6 for missing data. The median age at diagnosis was 65 years (IQR, 52–71) and 95% of participants were male (Table 1). 70% of participants received a first-generation TKI as first-line therapy; in the second-line setting, 12% received a first-generation TKI and 83% received a second-generation TKI. The median BCR-ABL level at asciminib initiation was 1.03 (IQR, 0.08–29.95) and decreased to 0.05 (IQR, 0–0.69) at 6 months. 11 patients developed thrombocytopenia and 3 developed neutropenia. Assuming 5 years of follow-up from the start of asciminib, RMST is 3.3 years (standard error, 0.23 years). Conclusions: Asciminib demonstrated clinically meaningful activity in a heavily pretreated Veteran population with CML. By 6 months, the median BCR-ABL level was 0.05%, consistent with major molecular response (MMR; BCR-ABL ≤0.1%), a well-established positive prognostic indicator. Despite prior exposure to multiple therapies, overall survival (using RMST) remained favorable at a mean of 3.3 years following treatment initiation. Rates of any-grade neutropenia and thrombocytopenia were low, supporting a favorable safety profile. Patient characteristics and outcomes. Characteristic Total (N = 110) Age at diagnosis, median (IQR) 65 (52–71) Gender, n (%) Male 105 (95%) Female 5 (4.5%) Race Black 19 (17%) White 85 (77%) American Indian or Alaska Native 1 (0.9%) Unspecified 5 (4.5%) Treatment Exposure First-line therapy 1 st generation TKI 77 (70%) 2 nd generation TKI 33 (30%) Second-line therapy 1 st generation TKI 13 (11.8%) 2 nd generation TKI 91 (82.7%) 3 rd generation TKI (ponatinib) 6 (5.5%) Outcomes Thrombocytopenia 11 (10%) Neutropenia 3 (2.7%) RMST (5 years), years 3.3 (95% CI, 2.9–3.8)
Palliative quad-shot radiation therapy in combination with low dose systemic treatment in advanced head and neck cancer.
e18024 Background: Head and neck cancer (HNC) is one of the most common cancers in Pakistan. Advanced stage is the most common presentation due to illiteracy and lack of optimum health care facilities. Concurrent chemoradiation is most commonly used treatment modality in these patients. We tested relatively less toxic systemic therapy using low dose capecitabine and afatinib in patients with locally advanced HNC combined with Quad-shot radiation therapy (QRT). Methods: A total of 93 patients with biopsy proven HNC with performance status of 2 or lower were included. Patients with primary tumor in oral cavity (41), oropharynx (19), hypopharynx (21) and larynx (12) with TNM stage III to IVB were selected. The patients were planned for low dose therapy (LDT) comprising capecitabine 500 mg twice daily and afatinib 40 mg daily. During this treatment, patients were planned for QRT. A total dose of 14 Gray (Gy) was planned with 3.5 Gy per fraction and two fractions a day at least six hours apart for two consecutive days. This protocol was repeated after a gap of one month. A maximum of three QRT sessions were planned. LDT was continued during this period until either patient progressed or develop toxicity. Response was assessed at the end of each month before delivering next QRT. Hematological, mucosal and skin toxicity were also assessed monthly during the treatment time. Progression free survival (PFS) and Overall survival (OS) were calculated at 3 years from randomization. Results: Out of total ninety-three patients, eighty-four patients completed at least two months of treatment. A total of 9 patients (11%) progressed during the treatment and were shifted to other treatment options. A total of 12 patients (14%) had complete response, 43 patients (51%) had partial response and 20 patients (24%) had stable disease. A total of 31 patients (37%) developed grade 1/2 anemia, 18 patients (21%) developed grade 1/2 neutropenia, and 13 patients (15%) developed grade 1/2 thrombocytopenia. A total of 46 patients (55%) developed grade 1/2 oral mucosal toxicity and 13 patients (15%) developed grade 3/4 oral mucosal toxicity. A total of 35 patients (42%) developed grade 1/2 skin toxicity and 9 patients (11%) developed grade 3/4 skin toxicity. Three-year PFS and OS were 31% and 44% respectively. Mean and median PFS (years) were 2.07±0.19 (95% confidence interval [CI] 1.69 to 2.45) and 1.18±013 (95% CI 0.92 to 1.44) respectively. Mean and median OS (year) were 2.57±0.20 (95% CI 2.17 to 2.97) and 2.11±0.15 (CI 1.81 to 2.41) respectively. Conclusions: Low dose systemic treatment in combination with QRT is a reasonable option in locally advanced HNC. However, a larger randomized trial is warranted to define its role before being routinely recommended.
Structured exercise program following adjuvant chemotherapy for colon cancer: A cost-utility analysis of the CHALLENGE trial.
3507 Background: The phase III CHALLENGE trial (CCTG CO.21) demonstrated improved disease-free and overall survival with a 3-year structured exercise program (SEP) compared with health education materials (HEM) in participants with stage III or high-risk stage II colon cancer that had undergone surgery and adjuvant chemotherapy. This study evaluated the cost-effectiveness of SEP versus HEM. Methods: A pre-specified economic evaluation was conducted using prospectively collected data from all trial participants (n = 889). The base case adopted the Canadian public healthcare payer perspective and included direct healthcare costs (cost categories available in Table 1), a 5-year time horizon, and a 1.5% discount rate. SF-36 trial data were mapped to SF-6D using a validated algorithm to calculate health utilities. Costs (2024 CAD) and effects measured as life-years (LYs) and quality-adjusted life-years (QALYs) were used to estimate an incremental cost-effectiveness ratio (ICER, $/life year gain (LYG)) and incremental cost-utility ratio (ICUR, $/QALY). Uncertainty was assessed via bootstrapping (n = 1,000). Notable scenario analyses included a 10-year horizon and a societal perspective capturing indirect costs from wages lost due to missed work, measured using a Work Productivity and Activity Impairment questionnaire. Results: In the base case, despite the up-front $4327 cost of the SEP intervention, the SEP was dominant over HEM (i.e less costly (−$179) and more effective (+0.06 LYs; +0.10 QALYs)). The SEP was dominant in 49% of bootstrap samples, while 79% met a $50,000 per QALY willingness-to-pay threshold. Major cost drivers in both groups were the costs of recurrence or new malignancy and anticancer therapy. Scenario analysis results were consistent with the base case analysis. The SEP remained dominant with a 10-year time horizon yielding greater cost savings ($-2,528) and more LYG (0.35) than the base case. From a societal perspective, the ICUR was $3,571/QALY, a highly cost-effective strategy. Conclusions: The SEP was less costly and more effective when compared with HEM. These data can inform health systems and payers as they look to implement SEP in routine models of care. Mean per participant costs, effects, and ICER/ ICUR for the base case analysis. SEP(n=445) HEM(n=444) Increment Cost of SEP sessions (including fixed start-up costs) ($) 4,327 0 4,327 Cost of hospitalization (pre- or without recurrence) ($) 3,593 3,092 501 Cost of recurrence or new malignancy (physicians, lab tests, drugs, hospitalizations, surgery, emergency room visits, home care)($) 12,732 15,772 -3,040 Cost of anticancer therapy ($) 12,660 14,582 -1,922 Cost of end-of-life care ($) 54 100 -46 Total cost ($) 33,367 33,546 -179 Total LYs 4.72 4.66 0.06 Total QALYs 3.84 3.75 0.09 ICER ($/LYG) and ICUR ($/QALY) Dominant* *SEP is less costly and more effective than HEM.
Timing of telepalliative care and end-of-life outcomes in advanced cancer: A multicenter retrospective cohort study.
1518 Background: Telemedicine has become an integral component of palliative care delivery; however, its impact on end-of-life outcomes in oncology remains insufficiently explored, particularly in low- and middle-income countries (LMICs). Place of death is a key quality indicator in palliative oncology and reflects goal-concordant care. This study evaluated whether the timing of palliative care teleconsultations was associated with a higher likelihood of home death among patients with advanced cancer receiving care in a Brazilian multicenter setting. Methods: We conducted a multicenter retrospective cohort study in Brazil including adults with advanced cancer who received interdisciplinary palliative care and died due to disease progression between January 1, 2024, and December 31, 2025. Exposure to telepalliative care was defined according to the timing of teleconsultations relative to death (any teleconsultation, ≤7 days, ≤30 days, or exclusively in-person care). The primary outcome was place of death (home vs other). Secondary outcomes included intensive care unit (ICU) admission and receipt of disease-modifying therapy in the last 30 days of life. Given the sample size, associations were evaluated using univariate logistic regression. Results: Among 116 patients (median age 65 years; 55% female), 63 (54.3%) received telepalliative care. Exposure to telepalliative care overall, irrespective of timing, was not associated with home death. In contrast, telepalliative care delivered closer to death was significantly associated with a higher likelihood of home death, particularly when performed within the last 7 days of life (OR 5.93; 95% CI 1.75–20.15; p = 0.004) and within the last 30 days (OR 3.08; 95% CI 1.04–9.10; p = 0.042). Telepalliative care was also associated with lower odds of ICU admission in the last 30 days of life (OR 0.34; 95% CI 0.16–0.73; p = 0.006) and reduced odds of receiving disease-modifying therapy in the final month of life (OR 0.35; 95% CI 0.15–0.79; p = 0.012). Conclusions: In this Brazilian multicenter retrospective cohort, the timing of telepalliative care, rather than teleconsultation exposure alone, was a key determinant of end-of-life outcomes. Telepalliative care delivered closer to death was associated with a higher likelihood of home death and reduced use of high-intensity end-of-life care. These findings highlight the importance of timely integration of telepalliative care to maintain continuity of interdisciplinary care and support goal-concordant end-of-life care, particularly in resource-constrained and geographically diverse settings.
Rapid multi-task intraoperative diagnosis of lung cancer via deep neural network-driven label-free femtosecond laser imaging (FLI).
8019 Background: Rapid and accurate intraoperative pathological diagnosis is critical for guiding surgical margins and preserving lung function during lung cancer surgery. Current frozen-section (FS) analysis is time-consuming and prone to artifacts. Femtosecond label-free imaging (FLI) enables high-resolution, non-destructive tissue visualization without staining or freezing, offering a promising platform for real-time assessment. Methods: We developed FastLung, an integrated FLI+AI platform for multi-task diagnosis. Fresh, unprocessed tissue samples (326 paired tumor-normal specimens) from surgical resections were imaged using multimodal FLI. FastLung employs a self-supervised deep learning model trained on ~4 million image patches, with formalin-fixed paraffin-embedded (FFPE) histopathology as ground truth. The system provides malignancy probability maps and categorical outputs within 5 minutes. Results: FastLung achieved high diagnostic performance across key intraoperative tasks: benign vs. malignant (AUC = 0.9854 ± 0.01), invasive vs. minimally invasive adenocarcinoma (AUC = 0.9573 ± 0.03), and adenocarcinoma vs. squamous cell carcinoma (AUC = 0.9892 ± 0.009). It significantly reduced diagnostic turnaround time (5–10 min vs. 20–30 min for FS, 60–80% faster) while maintaining accuracy comparable to or exceeding FS. In core needle biopsies (n = 94), accuracy reached 95.8%. The platform also demonstrated consistent performance across operators and time, supporting reliable integration into surgical workflow. Conclusions: FastLung combines label-free FLI with deep learning to deliver rapid, accurate, and reproducible intraoperative diagnosis of lung cancer, outperforming frozen sections in speed and multidimensional assessment. Its robust performance in both resection and biopsy specimens highlights its potential to improve surgical decision-making and extend toward pan-cancer diagnostic applications.
The early-onset paradox of gastric cancer: Assessment of geographic clustering, biology, treatment, and outcomes.
4088 Background: Early-onset gastric cancer (EOGC), defined as diagnosis before age 45, represents an increasingly recognized and clinically distinct subset of gastric cancer (GC) in the United States. While prior studies largely from Asian cohorts suggest more aggressive tumor biology, contemporary U.S. data characterizing demographic patterns, treatment strategies, geographic variation, and outcomes in resectable disease is limited. Methods: Using a U.S. cancer registry (2006–2022), we studied patients aged 18–90 with stage II–III gastric cancer post-gastrectomy. Excluding palliative or incomplete cases, we analyzed overall survival (OS) via Cox models, adjusting for demographics and treatment. P-values were calculated using the Chi-square test to compare racial distribution across age groups. Results: Among eligible patients, 1,943 (7.4%) had EOGC. EOGC disproportionately affected Hispanic (23.8%; p < 0.001), Black (14.2%; p < 0.001), and Asian (10.2%; p < 0.001) populations, with White patients accounting for 49.4%, with a male predominance (2:1). Demographic and socioeconomic profiles were distinct within the EOGC population. A greater proportion of EOGC patients resided in areas with a median household income < $38,000 (17.1%; p = 0.025). The ≤45 group was more frequently uninsured (7.6%) or Medicaid insured (19.7%) and represented the highest proportion of residents from areas with the lowest educational attainment (21.6%). Geographic clusters emerged in the South/Middle Atlantic and Pacific (TX, CA, AK, HI). EOGC tumors more frequently exhibited diffuse or signet-ring histology (~30%) and advanced nodal involvement. Despite receiving more intensive multimodality therapy, including perioperative or neoadjuvant chemotherapy (74.1%), EOGC patients had lower pathologic response rates and no survival advantage. Median OS was 49.8 months (36-month OS: 58.3%). Conclusions: Even with aggressive treatment, EOGC shows worse pathology and no better survival rates than older-onset cases. New U.S. data confirms this aggressive biology and highlights significant demographic and socioeconomic disparities. To improve outcomes, the focus should shift from just intensifying treatment to prioritizing earlier detection and targeted regional screening. Demographic characteristics stratified by age groups. Variable ≤45 Years (n=1943) 46–69 Years (n=15927) ≥70 Years (n=8397) Total Cohort (N=26267) p-value Race, n (%) <0.001 White 960 (49.4) 10912 (68.5) 5918 (70.5) 17790 (67.7) Black 276 (14.2) 1890 (11.9) 838 (10.0) 3004 (11.4) Hispanic 462 (23.8) 1611 (10.1) 766 (9.1) 2839 (10.8) Asian 198 (10.2) 1166 (7.3) 731 (8.7) 2095 (8.0) Other 47 (2.4) 348 (2.2) 144 (1.7) 539 (2.1)
Incidence of colorectal cancer in renal transplant recipients compared with the general population and inflammatory bowel disease: A population-based real-world cohort study.
e15707 Background: Chronic immunosuppression following renal transplantation is associated with an increased risk of malignancy; however, the relative incidence of increased malignancy risk remains poorly defined. The relative incidence of colorectal cancer (CRC) among renal transplant recipients compared with both the general population and other high-risk groups remains poorly defined. We evaluated CRC incidence in renal transplant recipients relative to individuals without a solid organ transplantation history and to patients with inflammatory bowel disease (IBD). Methods: We conducted a retrospective cohort study using real-world data from the TriNetX US federated research network. Adult renal transplant recipients were identified using CPT (50360, 50365), ICD-10 (Z94.0), and ICD-10-PCS (0TY00Z0) codes. Two comparator cohorts were constructed: (1) individuals without solid organ transplantation, IBD (ICD-10 K50, K51), or family history of digestive malignancy (Z80.0), and (2) patients with IBD without prior transplantation. Patients with pre-existing CRC were excluded. Propensity score matching was not feasible due to limited cohort size. Incident CRC was defined using ICD-10 codes C18–C20 and evaluated with Cox proportional hazards models, reported as risk ratios (RRs) with 95% confidence intervals (CIs). Results: The final analytic cohort consisted of 166,422 renal transplant recipients, 596,934 patients with IBD, and 46,820,315 individuals in the general comparator cohort. During follow-up, renal transplant recipients demonstrated a significantly higher incidence of CRC compared with the general population Risk Ratio (RR 1.75, 95% Confidence Interval CI 1.63–1.87; p < 0.0001). In contrast, CRC incidence among renal transplant recipients was significantly lower than that observed in patients with IBD (RR 0.78, 95% CI 0.72–0.84; p < 0.0001). Subgroup analyses demonstrated that these associations were consistent across age categories, including younger adults (18–45 years) and older adults (45–80 years), with no meaningful attenuation of effect by age. Conclusions: In this large real-world cohort, renal transplant recipients exhibited an intermediate risk of CRC, with an incidence higher than that of the general population but lower than that of patients with IBD. These findings support the consideration of risk-stratified CRC screening strategies in transplant populations and provide real-world evidence to inform surveillance approaches in chronically immunosuppressed populations. Outcome General Population HR (95% CI) p Value Inflammatory Bowel Disease HR (95% CI) p Value Malignant neoplasms 1.75 (1.63–1.87) <0.0001 0.78 (0.72–0.84) <0.0001 Benign neoplasms 1.65 (1.61–1.68) <0.0001 0.61 (0.60–0.60) <0.0001 Colonoscopies 1.78 (1.75–1.80) <0.0001 0.37 (0.30–0.31) <0.0001
GLP-1 receptor expression in a molecularly characterized cohort of endometrial carcinoma: Results from the GEICO 163-T/SPECTRUM study.
5625 Background: The glucagon-like peptide-1 receptor (GLP-1R) plays a central role in metabolic, and hormonal signaling and has gained increasing clinical relevance due to the widespread use of GLP-1R agonists. Given the strong link between obesity and endometrial carcinoma (EC), data on GLP-1R expression in EC are of clinical interest. We aimed to evaluate GLP-1R expression in a large, molecularly classified EC cohort and analyze its association with clinicopathological and molecular features. Methods: GLP-1R immunohistochemistry was performed on tissue microarrays from 192 ECs included in the SPECTRUM cohort. This cohort included 111 low grade endometrioid and 81 high grade ECs. 187 tumors were successfully classified according to WHO 2020 criteria, including 3% POLE-mutated (POLEmut), 25% mismatch repair–deficient (dMMR), 43% no specific molecular profile (NSMP), and 29% p53 abnormal (p53abn) carcinomas. Additionally, CTNNB1 mutation status was available in 168 tumors (16% mutated). GLP-1R expression was evaluated using the Allred scoring system (range 0–8). GLP-1R positivity was defined as Allred ≥6 according to previously published criteria (Kanda et al. 2018). Associations were evaluated using univariable analyses and multivariable logistic regression, reporting ORs with 95% confidence intervals; p<0.05 was considered statistically significant. Results: GLP-1R expression was evaluated in 172 EC. GLP-1R positivity was observed in 32.0% of the overall cohort and differed across molecular subtypes: 41.9% in NSMP, 40.0% in POLEmut, 28.9% in p53abn and 20.5% in dMMR tumors (p=0.099). Progesterone receptor (PR) levels were significantly higher in GLP-1R–positive compared with GLP-1R–negative tumors (median 55% vs 20%, p=0.015), whereas a non-significant trend toward higher estrogen receptor (ER) expression was observed (median 50% vs 25%, p=0.18). GLP-1R positivity was more frequent in CTNNB1 mutated tumors (50.0% vs 28.9%; p=0.041). In multivariable logistic regression including PR (continuous), CTNNB1 mutation status and molecular classification, only PR levels remained independently associated with GLP-1R positivity (OR per 10% increase 1.15, 95% CI 1.02–1.30; p = 0.019). Conclusions: GLP-1R is frequently expressed in EC, particularly in PR positive tumors and within the NSMP molecular subtype, suggesting that the underlying pathway of carcinogenesis may influence GLP-1R expression. These findings may inform the design of future translational and clinical studies exploring GLP-1R–targeted strategies in endometrial carcinoma.