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Use of multi-omics biomarkers to predict benefit from immune checkpoint inhibitors in biliary tract cancers: A systematic review and meta-analysis.
e14587 Background: Predictive biomarkers for immune checkpoint inhibitors (ICIs) in biliary tract cancers (BTC) are urgently needed. Multi-omics platforms including genomics, transcriptomics, spatial profiling and proteomics have emerged as promising tools. We evaluated the pooled predictive performance of omics-based biomarkers for ICI benefit in BTC. Methods: We searched PubMed, Embase and Scopus (2020-2025) for studies assessing pre-treatment omics biomarkers in ≥20 adult BTC patients receiving PD-1/PDL1 therapy; four studies used multi-omics profiling and two used single-omics. Primary outcomes were progression free survival (PFS), overall survival (OS) and predictive accuracy (AUC), analyzed using random-effects meta-analysis with Knapp-Hartung (KH) adjustment. Hazard ratios (HR) were harmonized so biomarker-positive groups consistently represented superior outcomes; regimens included ICI monotherapy and ICI combined with chemotherapy and pooled estimates used each study’s own biomarker cut-offs. Pooled AUC was derived from the three ROC-reporting studies and survival from the four HR-reporting studies, with subgroups (immune-activation, genomic-instability, negative-predictor and liquid vs tissue biomarkers), leave-one-out sensitivity analyses and a reviewer derived pathway convergence map linking reported genes and proteins to canonical immune pathways. RoB and certainty evaluated using QUIPS and GRADE. Results: Six studies including 443 participants met criteria. For PFS, the pooled HR was 0.23 (95%CI 0.094–0.558; KH CI 0.087–0.602; I 2 = 58%). For OS, the pooled HR was 0.24 (95%CI 0.084–0.711; KH CI 0.097–0.628; I 2 = 47%) with leave-one-out analyses showing stable estimates. Funnel plot suggested possible small study/publication bias and formal tests were limited by the number of studies. Predictive accuracy values ranged 0.831–0.867; pooled AUC (from the three studies with ROC data) was 0.858 (95%CI 0.797–0.918). Subgroup analyses showed no differences across immune-activation, genomic-instability or negative-predictor biomarkers (P > 0.7) and no difference between liquid vs tissue biomarkers for PFS or OS (P > 0.3). Pathway mapping showed convergent IFN-γ signaling, chemokine-mediated T/NK recruitment, antigen processing pathways and spatial immune niches. RoB was moderate in four studies and high in two; overall GRADE certainty was moderate. Conclusions: Across omics platforms, biomarker-positive BTC patients showed markedly improved PFS and OS (~75% risk reduction) and strong predictive accuracy. Despite heterogeneous biomarker definitions and regimens, a convergent immune-responsive phenotype identifies ICI-sensitive BTC and supports prospective biomarker stratified trials using standardized assays to validate these signals and prioritize patients for ICI-containing regimens pending validation.
Correlation of PD-L1 expression with tertiary lymphoid structure maturity and immune cell spatial distribution in colorectal cancer.
e15582 Background: PD-L1 expression is a key biomarker for predicting immune checkpoint inhibitor (ICI) efficacy but shows significant interpatient heterogeneity in colorectal cancer (CRC), suggesting the complex tumor immune microenvironment (TIME) may affect its predictive value. Mature tertiary lymphoid structure (TLS) formation is associated with favorable prognosis and enhanced ICI response. However, the relationship between PD-L1 expression, TLS maturity, and spatial localization of different immune cell subsets remains unclear. Methods: We included 474 CRC patients whose TIME was profiled using multiplex immunohistochemistry (mIHC) and an AI-based image analysis system (Timepro platform). Spearman's rank correlation analyzed PD-L1 metrics [tumor proportion score (TPS) and combined positive score (CPS)] with the density/proportion of TLSs and immune cells in tumor parenchyma and stroma. P-values were corrected for multiple testing. Results: PD-L1 expression showed no significant correlation with TLS density or proportion, suggesting TLS maturity may be independent of PD-L1 and serve as a complementary biomarker for ICI response, particularly in PD-L1-low/negative patients. PD-L1 TPS was weakly negatively correlated with stromal CD8+ T-cell proportion ( ρ = -0.188, p < 0.01), density/proportion of CD68+CD163+ M2 macrophages in both parenchyma and stroma ( ρ range: -0.179 to -0.201, p < 0.01), and density/proportion of CD68+CD163- M1 macrophages in parenchyma ( ρ = -0.196, -0.200, p < 0.01). A weak negative correlation was also observed with stromal FoxP3+ T-cell proportion ( ρ = -0.174, p < 0.05). In contrast, PD-L1 CPS was weakly positively correlated with density/proportion of CD8+ T cells ( ρ range: 0.174-0.192, p < 0.05), M2 macrophages (ρ range: 0.210-0.251, p < 0.001) in both parenchyma and stroma, M1 macrophage ( ρ = 0.228, 0.223, p < 0.001) in parenchyma, and FoxP3+ T-cell proportion ( ρ = 0.172, p < 0.05) in stroma. These findings indicate that PD-L1 CPS positively correlates with broad immune cell infiltration in CRC, potentially better identifying patients with an immunologically active yet PD-L1-mediated adaptive resistance phenotype. Tumor-associated macrophages (TAMs) may be key regulators of PD-L1 expression in the CRC TIME. The strong correlation between PD-L1 and TAMs supports future exploration of combined TAM-targeted and PD-L1 inhibitor therapies to reverse immunosuppression and enhance efficacy. Conclusions: TLS is a PD-L1-independent biomarker in CRC. The opposing correlations of PD-L1 TPS and CPS with immune infiltration underscore the importance of scoring methodology. PD-L1 CPS reflects an immune-active, adaptive-resistant microenvironment. Combined assessment of TLS, PD-L1 CPS, and spatial immune architecture may improve immunotherapy stratification.
Indocyanine green–guided lymphadenectomy in gastrectomy for gastric cancer: A systematic review and meta-analysis.
e16098 Background: Indocyanine green (ICG) near-infrared fluorescence is increasingly used to guide lymphadenectomy during laparoscopic gastrectomy for gastric cancer, but its true impact on oncologic outcomes and perioperative safety compared with conventional surgery remains unclear. This systematic review and meta-analysis evaluated whether ICG guidance meaningfully improves long-term outcomes and surgical quality in adults undergoing laparoscopic radical gastrectomy for resectable gastric adenocarcinoma. Methods: We systematically searched PubMed, Scopus, Web of Science, and the Cochrane Library up to October 2025 for randomized trials and comparative cohort studies comparing ICG fluorescence–guided lymphadenectomy with conventional laparoscopic gastrectomy. Adults with resectable gastric adenocarcinoma undergoing laparoscopic radical gastrectomy were included. Random-effects models were used to pool effect estimates. Results: Across several randomized and non-randomized studies, including tens of thousands of patients overall, ICG-guided surgery achieved similar 5-year (RR 0.99, 95% CI 0.87–1.12) and 2-year (RR 1.03, 95% CI 0.95–1.12) overall survival compared with conventional surgery. Despite this, ICG was associated with clear oncologic advantages: overall recurrence was significantly reduced (RR 0.57, 95% CI 0.43–0.76), and primary tumor recurrence was markedly lower (RR 0.19, 95% CI 0.07–0.52). Early postoperative mortality was also reduced with ICG guidance (RR 0.60, 95% CI 0.40–0.90). From a surgical standpoint, ICG-guided lymphadenectomy retrieved more lymph nodes than standard surgery (MD – 5.41 nodes, 95% CI 3.38–7.43), without increasing the number of metastatic nodes, suggesting improved staging rather than stage inflation. ICG use was associated with a modest reduction in operative time and a shorter postoperative hospital stay (MD −0.63 days, 95% CI −0.97 to −0.30), while intraoperative/estimated blood loss, recovery of bowel function, conversion to open surgery, resection margins, and readmission rates were broadly similar between groups. Overall postoperative complications were slightly but significantly lower with ICG (RR 0.87, 95% CI 0.76–1.00), and there was no signal of increased major (Clavien–Dindo III–V) complications. Conclusions: ICG fluorescence–guided provides meaningful technical and clinical advantages: it increases lymph node yield, reduces recurrence and early postoperative mortality, and lowers overall complication risk, all without compromising overall survival or increasing perioperative harm. These findings support ICG guidance as a safe, effective adjunct to standard laparoscopic gastrectomy for gastric cancer. Standardized ICG protocols and further large, high-quality trials are still needed to confirm long-term oncologic benefits and define best practice.
Efficacy and safety of deulorlatinib (TGRX-326) in patients with locally advanced or metastatic ALK+ non–small cell lung cancer: A multicenter, open-label, pivotal phase 2 trial.
8638 Background: Treatment options are limited for anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients (pts) who have developed resistance to second-generation ALK inhibitors. Deulorlatinib is a highly potent third-generation ALK inhibitor. The Previous phase 1 study (NCT05441956) found that deulorlatinib had a high overall and intracranial response rate in pts who had progressed on second-generation inhibitors, with encouraging activity against the G1202R mutation and favorable tolerability. Methods: This is a multicenter, open-label pivotal phase 2 study. Pts with locally advanced or metastatic ALK+ NSCLC who had progressed on second-generation inhibitors received deulorlatinib 60 mg orally once daily. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by independent review committee (IRC). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. The ORR in patients harboring the G1202R mutation was also assessed. Results: Between Jan 18, 2023 and Dec 29, 2023, a total of 163 patients were enrolled and 158 were evaluable for efficacy. Of these pts, the median age was 53.5 years old, 53.2% were female, 95.6% had adenocarcinoma, and 56.2% had baseline brain metastasis; 56.3% of these pts had progressed on alectinib. As of December 16, 2025, the median follow-up was 28.7 months and 44 pts were still on deulorlatinib. The IRC assessed confirmed ORR was 43.7% (95%CI 35.8, 51.8). The median DoR and PFS was 20.7 months (95%CI 15.4, NR) and 13.8 months (95%CI 8.3, 16.5), respectively; median OS was not reached. Of the 43 pts with measurable baseline CNS lesions, confirmed ORR was 55.8% (95%CI 39.9, 70.9). In pts with the G1202R mutation, the ORR was 62.5% (95%CI 24.5, 91.5). Treatment-related adverse events (TRAEs) were reported in 96.3% of pts. The most common TRAEs were hypercholesterolaemia (77.9%), hypertriglyceridaemia (71.2%), and weight gain (52.8%). Grade ≥3 TRAEs were reported in 51.5% of pts. Of note, only 1.2% of pts had Grade ≥3 CNS TRAEs. Conclusions: Deulorlatinib produced robust and durable responses in locally advanced or metastatic ALK+ NSCLC pts with progression on second-generation inhibitors, including those with the G1202R mutation, with low incidence of Grade ≥3 CNS TRAEs. Although across trials comparisons must be interpreted cautiously, deulorlatinib might have a better safety profile than lorlatinib. Altogether these findings suggest that deulorlatinib has a favourable risk benefit ratio and support its further development, particularly in the first-line setting. Clinical trial information: NCT05955391 .
Efficacy and safety analysis of hepatic arterial infusion chemotherapy plus PD-1/PD-L1 antibodies combined with donafenib or bevacizumab in patients with unresectable hepatocellular carcinoma.
e16155 Background: In unresectable hepatocellular carcinoma (uHCC), it is unknown whether donafenib plus hepatic arterial infusion chemotherapy (HAIC) and PD-1/PD-L1 antibodies (DonaHP) shows comparable efficacy and safety to bevacizumab plus HAIC and PD-1/PD-L1 antibodies (BevHP). This study aimed to compare the efficacy and safety of DonaHP and BevHP as first-line treatments for unresectable HCC. Methods: Patients who were diagnosed with uHCC and initially treated with DonaHP or BevHP at the Sun Yat-sen University Cancer Center between April 2022 and July 2023 were retrospectively enrolled. The primary outcome was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR), all of which were assessed according to RECIST v1.1, as well as safety. Propensity score matching (PSM) was performed to balance patient characteristics between the two groups. Results: In total, 175 patients (64 in the DonaHP group and 111 in the BevHP group) were included. The mean age was 54.1 years, and 163 (93.1%) patients were male. The median intrahepatic tumor size was 9.8 cm, and multiple tumors were recorded in 134 (76.6%) patients. Macrovascular invasion and extrahepatic metastases were present in 92 (52.6%) and 33 (18.9%) patients, respectively. Before PSM, The 1-, 2-, and 3-year OS rates were 85.3%, 63.1% and 57.8% in the DonaHP group versus 78.6%, 52.7% and 44.1% in the BevHP group (HR: 0.712, 95% CI: 0.448–1.132, P = 0.174). The median PFS was 15.3 months versus 10.3 months (HR: 0.595, 95% CI: 0.411–0.863, P = 0.010). According to RECIST v1.1, the ORR was 48.4% versus 49.5% (P > 0.999), and the DCR was 93.8% versus 86.5% ( P = 0.217). After PSM, 57 patients were included in each group, the 1-, 2-, and 3-year OS rates were 89.0%, 67.2% and 61.3% in the DonaHP group versus 81.8%, 47.9% and 38.5% in the BevHP group (HR: 0.532, 95% CI: 0.304–0.932; P = 0.033). The median PFS was 16.2 months versus 8.1 months (HR: 0.575, 95% CI: 0.359–0.932, P = 0.019). There was no statistically significant difference in the overall incidence of adverse events (AEs) between the DonaHP group and the BevHP group ( P = 0.366), although distinct patterns of specific AEs were observed. Twenty-one (32.8%) patients in the DonaHP group experienced grade 3/4 AEs, whereas 38 (33.8%) patients in the BevHP group experienced grade 3/4 AEs ( P = 0.848). Conclusions: Donafenib plus HAIC and PD-1/PD-L1 antibodies has potential superior anti-HCC efficacy compared with bevacizumab plus HAIC and PD-1/PD-L1 antibodies.
A prospective, single-arm, exploratory study on the efficacy and safety of romiplostim N01 for cancer treatment–induced thrombocytopenia in patients with gastrointestinal cancers.
e16346 Background: Cancer Treatment-Induced Thrombocytopenia (CTIT) is a common complication in patients with gastrointestinal (GI) cancers, often leading to treatment delays, dose reductions, and increased bleeding risk. Romiplostim N01 is recommended for CTIT but lacking specifically evidence in GI cancer. This study aims to explore the efficacy and safety of Romiplostim N01 in GI cancer patients with CTIT. Methods: This prospective, single-arm, multi-center study conducted from July 2025 to June 2027. 100 adult patients with GI cancers and developed CTIT (platelet count < 50×10⁹/L) following anticancer therapy will be enrolled. Patients received subcutaneous Romiplostim N01 (starting dose 3 µg/kg/week) for up to 8 weeks. The primary endpoint was the proportion achieving platelet count ≥50×10⁹/L at week 2 after treatment initiation. Secondary endpoints included the proportion of patients achieving a platelet response (increase ≥ 50×10⁹/L without transfusion) within 7 days, time to platelet recovery (≥50×10⁹/L, ≥100×10⁹/L), transfusion requirements, and safety. Results: As of January 20, 2026, a total of 21 subjects were enrolled (14 males, 7 females) with a median age of 67 years (range, 53-76). Primary tumor types included rectal cancer (23.8%, 5/21), colon cancer (19.0%, 4/21), cholangiocarcinoma (19.0%, 4/21), with the remaining being gastric cancer (3/21) and others. Most patients (20/21) had an ECOG status of 0-2. Thirteen patients had previously received immunotherapy, while the others underwent standard chemotherapy. Eighteen subjects received one dose of Romiplostim N01 (3 µg/kg/week), and three received two doses. The median baseline platelet count was 37×10⁹/L (range, 32-42×10⁹/L). Nineteen subjects (90.5%, 19/21) achieved the primary endpoint (platelet count ≥50×10⁹/L) within two weeks, and the median platelet count after response was 76×10⁹/L (range, 55-137×10⁹/L). The median time to platelet recovery ≥50×10⁹/L was 7 days (95% CI, 2.734-11.266), and the median time to platelet recovery ≥100×10⁹/L was 13.5 days (95% CI, 7.5-29.5). No patient required additional platelet transfusions. Adverse events were mild to moderate, primarily arthralgia and headache, and all resolved. No treatment-related serious adverse events (SAEs) were reported. Conclusions: Romiplostim N01 shows promising efficacy for CTIT in GI cancers, with most patients achieving rapid platelet recovery (median 7 days) and no need for transfusions. The manageable safety profile suggests it is a viable supportive care option. These findings will provide further support for its clinical use. Clinical trial information: ChiCTR2500106841.
NOGA: Neoadjuvant treatment optimization via MRI-guided de-escalation in stage II–III TNBC—A phase 2 study.
TPS654 Background: Pembrolizumab combined with neoadjuvant chemotherapy improves pathological complete response (pCR) rates and survival in stage II–III triple-negative breast cancer (TNBC), establishing the KEYNOTE-522 regimen as the standard of care. This regimen consists of two phases: four cycles of paclitaxel/carboplatin with pembrolizumab (TCa+P), followed by four cycles of adriamycin/cyclophosphamide with pembrolizumab (AC+P). However, anthracycline-containing chemotherapy contributes substantial short- and long-term toxicity. A subset of patients may achieve pCR after the initial TCa+P phase, raising the possibility that treatment intensity may be reduced in selected responders. Breast MRI demonstrates high concordance with pCR in hormone receptor–negative breast cancer and represents a promising, noninvasive biomarker to guide response-adapted de-escalation strategies. Methods: This is a prospective, investigator-initiated, multicenter, single-arm phase II trial evaluating MRI-guided de-escalation of neoadjuvant chemotherapy plus immunotherapy in patients with early TNBC. Eligible patients have Stage II-III (T2-T3N0 or T1-T3N1) TNBC and are candidates for the KEYNOTE-522 regimen. All patients receive four cycles (12 weeks) of TCa+P, followed by mid-treatment breast MRI. Patients achieving radiologic complete response (MRI-CR) proceed directly to surgery, omitting anthracycline-containing chemotherapy. Patients with radiologic residual disease (MRI-RD) complete the full neoadjuvant regimen including AC+P. The primary endpoint is pCR rate among patients with MRI-CR undergoing early surgery. Key secondary endpoints include recurrence-free survival, overall survival, toxicity, and patient-reported outcomes. Exploratory analyses include longitudinal circulating tumor DNA (ctDNA) dynamics to assess early molecular response, minimal residual disease, and correlates with MRI-CR, pCR, and long-term outcomes. The expected pCR rate among patients achieving MRI-CR is ≥87%, compared with a benchmark rate of 65%. The study uses a Simon’s optimal two-stage design (one-sided α=0.05, 80% power). In stage 1, 10 MRI-CR patients proceeding directly to surgery will be evaluated, with early stopping for futility if the efficacy threshold is not met. If successful, stage 2 will enroll an additional 17 MRI-CR patients, for a total of 27 evaluable patients. Assuming an MRI-CR rate of ~50%, 54 patients will be enrolled overall. The study is open for recruitment at two tertiary academic hospitals in Israel, and 9 of the planned 54 patients have been enrolled. The NOGA trial represents a novel precision oncology approach in early TNBC, with the potential to minimize toxicity without compromising efficacy in selected responders. Clinical trial information: NCT07327021 .
Real-world evidence of the association between primary insomnia and early-onset gastrointestinal cancers.
e23414 Background: Although progress has been made in reducing overall cancer incidence, early-onset cancers have continued their troublesome rise. Similarly, primary insomnia increases in incidence and prevalence each year, and with it come likelihoods of circadian disruption, immune dysregulation, and altered hormone signaling. However, real-world data characterizing the association between insomnia and early-onset gastrointestinal malignancies remains limited. Methods: We sought to conduct a real-world, retrospective cohort study using the TriNetX United States Research Database, a federated network of de-identified electronic health records (EHRs) from over 70 healthcare organizations, to examine this association. Adults aged 18–50 years with primary insomnia (ICD-10: F51.01) were compared with same-aged individuals without primary insomnia using a five-year lookback period from January 25th, 2021 to January 25th 2026. Propensity score matching adjusted for demographic and clinical confounders. Incidence of early-onset cancers diagnosed within five years of the index event was assessed during follow-up. Sensitivity analyses required a ≥ 1-year lag between insomnia diagnosis and cancer onset. Results: 413,116 patients ages 18-50 were identified as having primary insomnia, whereas 18,437,709 patients ages 18-50 were identified as not having primary insomnia. Within 1-5 years of primary insomnia diagnosis, patients were more likely to develop early-onset colorectal cancer (RR 1.853, CI 1.576-2.179, p < 0.0001). Associations with early-onset esophageal cancer (RR 1.632, CI 0.922-2.888), gastric cancer (RR 2.273, CI 1.377-3.752), pancreatic cancer (RR 1.245, CI 0.868-1.788), and biliary tract cancer (RR 2.300, CI 1.095-4.832) did not meet thresholds for significance. Conclusions: In this large, real-world cohort study, insomnia was associated with an increased risk of early-onset colorectal cancer relative to several other common early-onset gastrointestinal cancers. These findings suggest that sleep disruption may represent a clinically relevant, potentially modifiable risk factor in early-onset colorectal cancer specifically and warrants further investigation.
Real-world patient characteristics, treatment patterns and clinical outcomes in patients diagnosed with extra-pulmonary neuroendocrine carcinoma (epNEC): A non-interventional multimodal database analysis in the US.
e16310 Background: Extra-pulmonary neuroendocrine carcinomas (epNECs) represent a rare and aggressive subset of malignant neuroendocrine neoplasms associated with poor outcomes and an incidence rate of approximately 1 per 100,000 individuals. While evidence-based treatment recommendations are lacking, platinum-based chemotherapy, extrapolated from small cell lung cancer, remains the consensus first-line (1L) treatment with no standard in second-line (2L). Significant gaps persist in our understanding of epNEC, with limited data available on epidemiology, treatment, and outcomes. This study aims to characterize real-world patient characteristics, treatment patterns, and clinical outcomes in patients diagnosed with epNEC in the US. Methods: In this retrospective study, patients diagnosed with epNEC and treated with 1L therapy were identified from August 2012 to March 2025 using the Tempus multimodal dataset. The Tempus data model includes de-identified pan-cancer longitudinal data linked to claims data from the Komodo Healthcare Map. Baseline patient characteristics and treatment patterns were evaluated. Real-world progression-free survival (rwPFS) and overall survival (rwOS) were estimated using Kaplan-Meier risk-set–adjusted methods by line of therapy. Results: Of 146 patients diagnosed with epNEC and treated with 1L therapy (median age 61 years; 42% female; 56% white), most tumors originated from the gastrointestinal tract (82%) and 83% had stage III/IV disease at initial diagnosis. 1L treatment (N = 146) was predominantly platinum-etoposide-based (n = 122, 84%), with 62% (n = 90) receiving platinum-etoposide alone, supporting its role as the standard of care regimen in the 1L setting; 20% (n = 29) of patients received immunotherapy as part of their 1L treatment. Of all patients who received 1L treatment, median rwPFS and rwOS were 4.8 and 9.0 months. Among patients treated with 1L platinum-etoposide alone, median rwPFS and rwOS were 3.5 and 7.0 months. Among patients treated with 1L chemotherapy in combination with immunotherapy, median rwPFS and rwOS were 4.8 and 9.9 months. Of 1L-treated patients, 40% (N = 58) were treated with 2L therapy. 2L treatments were heterogeneous reflecting a lack of consensus or effective options after progression on 1L therapy. Median rwPFS and rwOS were 1.8 and 4.7 months in 2L. Conclusions: This real-world analysis demonstrates poor outcomes in patients diagnosed with epNEC, despite platinum-etoposide-based therapy as the consensus 1L standard of care. In the 2L setting, where standard of care treatment is lacking, survival continues to be poor demonstrating a high unmet need in this patient population. These data underscore the need for innovative treatment strategies to improve survival in this highly aggressive disease.
Rethinking clinical follow-up for breast cancer survivorship care: A narrative literature review.
e13797 Background: Breast cancer recurrence rates are declining with improvements in therapies. Earlier detection is facilitated by improvements in radiographic techniques, yet guidelines for clinical breast exam (CBE) remain the same. Current guidelines recommend follow-up visits with specialists every three to twelve months for the first five years after diagnosis then annually. More frequent follow-up visits provide unknown benefit while exacerbating financial toxicity for survivors and may delay care for new patients awaiting access to specialists. We sought to review and understand the evidence behind current recommendations to understand the utility of clinical surveillance for patients with low-risk breast cancer. Methods: We searched English-language PubMed sources, including randomized controlled trials (RCTs), retrospective cohort studies, systematic reviews, meta-analyses, cross-sectional studies, and guidelines. We focused on breast cancer surveillance after treatment, recurrence, follow-up schedules, costs of care, delays in treatment, and patient experience. The findings were synthesized thematically. Results: A review of the literature reveals mammography and breast self-exam are the primary methods of detection of local breast cancer recurrence. Of those detected by CBE, fewer than 1% were curable. Over half of local recurrences were identified outside of routine follow-up visits. Literature cites risk of local recurrence being 1% or less for most subtypes of breast cancer after three event-free years. Fewer than 10% of national follow-up guidelines are based on data from RCTs. Our review further reveals that 14% of survivors experience financial concerns and documents visit frequency exceeding guidelines. Many survivors report follow-up visits with multiple providers at a cadence that exceeds current guideline recommendations, regardless of treatment modality received. Comparing visits with specialists vs. primary care providers, both are rated as high-quality with no significant difference in health-related quality of life. Delays in time to surgery, radiation and/or systemic chemotherapy are associated with decreased survival. Conclusions: This literature review demonstrates limited benefit from frequent clinical surveillance and CBE. Clinical visits add expense to patients who are reporting increasing treatment-related financial toxicity. Although there is little level 1 evidence with which to redesign guidelines, this aggregate review of literature suggests modifications to current guidelines can decrease cost of care and potentially increase access for newly diagnosed patients without compromising patient satisfaction or outcomes. RCTs are needed in order to inform such modifications. Health systems must also work to improve coordination of care for in order to reduce redundancy in survivor follow-up care.
Effect of timely immunizations on infection-related outcomes after CLL-directed treatment.
e19032 Background: Patients with Chronic Lymphocytic Leukemia (CLL) are at a higher risk of developing infections due to disease related hypogammaglobulinemia, T cell dysfunction, neutropenia and the immunosuppressive effects of therapy. Data about mitigating infection risk with optimal vaccinations before treatment commences in CLL patients is sparse. Our study aims to evaluate the effect of pre-treatment vaccination on infection rates following therapy in patients with CLL. Methods: We performed a retrospective study across a large, multi-hospital healthcare system. The electronic health records were queried using ICD-10 codes to identify patients with CLL spanning a 10-year period between 1/1/2015 and 12/31/2024. Patients over 18 years of age who had a verifiable CLL diagnosis, longitudinal follow-up, and immunization records were included in the study. The primary outcome studied was the effect of pre-treatment vaccination status on post-treatment infection outcomes. Results: A total of 783 patients with CLL were identified, data were verified and were included in the analysis. 167 (21%) of these patients received treatment for CLL. 28 (17%) patients received chemoimmunotherapy, 56 (34%) patients received Venetoclax based therapy and 98 (59%) patients received a Bruton Tyrosine Kinase Inhibitor. Prior to treatment, 126/167 (75.4%) patients received influenza vaccination, 109/167 (65.3%) received pneumococcal vaccination, 83/167 (49.7%) received COVID-19 vaccination, and 73 (43.7%) received at least one dose of zoster vaccination. Overall, 25 (14.9%) vaccinated patients developed infections after starting therapy. 10/14 (71.4%) COVID infections occurred in those who had not received COVID vaccination prior to treatment while 4/14 (28.6%) occurred in those who had received COVID vaccine prior to treatment. Of the 14 patients who developed pneumonia, 10 had received pre-treatment pneumococcal vaccination while 4 had not received pneumococcal vaccination. Of the 3 shingles cases, 2 occurred in patients unvaccinated for shingles and one occurred in a vaccinated patient. Conclusions: Pre-treatment vaccination in CLL patients reduces risk of developing post treatment infection when compared to unvaccinated patients undergoing CLL therapy. Majority of patients who did not receive COVID vaccination prior to CLL therapy developed COVID infections after starting CLL therapy. Updating age-appropriate vaccinations prior to commencing CLL directed therapy is optimal.
Efficacy and safety of transarterial therapy combined with donafenib plus PD-1 inhibitors for unresectable hepatocellular carcinoma: A multicenter retrospective study.
e16171 Background: Triple therapy combining transarterial therapy, tyrosine kinase inhibitors (TKIs), and programmed death-1 (PD-1) inhibitors represents a promising therapeutic strategy for unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of transarterial therapy combined with donafenib (a TKI) and PD-1 inhibitors as first-line treatment in a real-world uHCC cohort. Methods: This was a multicenter, retrospective study conducted across five medical centers in China. We analyzed patients diagnosed with uHCC who had received at least one cycle of triple combination therapy comprising transarterial therapy (hepatic arterial infusion chemotherapy [HAIC] and/or transarterial chemoembolization [TACE]), donafenib, and PD-1 inhibitors. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), surgical conversion rate, and safety. Tumor responses were assessed according to both the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1. Results: After screening, 70 patients were included in the analysis. Key baseline characteristics were as follows: median age 55 years; 92.9% male; 87.1% with HBV infection; 60.0% at BCLC stage C. Additionally, 48.6% of patients had macrovascular invasion, 22.9% had extrahepatic metastasis, and 74.2% presented with multiple tumors, with a median maximum tumor diameter of 86.5 mm. The PD-1 inhibitors administered included tislelizumab (41.4%), camrelizumab (37.1%), sintilimab (18.6%), toripalimab (2.9%). Transarterial therapy regimens consisted of TACE plus HAIC (38.6%), HAIC alone (34.3%), and TACE alone (27.1%). After a median follow-up of 27.5 months, the median PFS was 12.7 months (95% CI, 8.4-23.8) per both mRECIST and RECIST v1.1. The median OS was 29.3 months (95% CI, 22.4-NA) with 12- and 24-month OS rates of 81.7% and 57.2%, respectively. The ORR was 67.1% per mRECIST and 52.9% per RECIST v1.1, and the DCR was 87.1% by both criteria. The surgical conversion rate was 22.9%. Treatment-related adverse events (TRAEs) occurred in 87.1% of patients, with grade 3-4 events in 37.1%. The most common TRAEs included liver dysfunction (51.4%), hand-foot skin reaction (47.1%), decreased platelet count (18.6%), and decreased white blood cell count (17.1%). Conclusions: This real-world study demonstrates that transarterial therapy combined with donafenib and PD-1 inhibitors provides encouraging survival outcomes and a manageable safety profile for uHCC patients. Clinical trial information: ChiCTR2200063822.
Final analysis of the investigator-initiated randomized study of anti–PD-L1 durvalumab (durva) with radiation versus chemoradiation (CRT) for intermediate-risk HPV-positive (HPV+) locally advanced oropharyngeal squamous cell carcinoma (LA-OPSCC): Canadian Cancer Trials Group (CCTG) HN.9 (EORTC 1740-HNCG).
6017 Background: Primary immunotherapy (IO) with radiotherapy remains an investigational approach in HPV+ LA-OPSCC. The CCTG-led international phase II, randomized, non-comparative, HN.9 (NCT03410615) trial evaluated the efficacy of the of durva+RT as a chemo-sparing approach in patients (pts) with intermediate-risk, HPV+, LA-OPSCC. Methods: Pts with newly diagnosed, PDL1-unselected, pathologically proven, treatment-naïve HPV+ LA-OPSCC (UICC/AJCC 8th Edition T1-2N1 or T3N0-1 smokers [≥10 pack years] or T1-3 N2 with any smoking history) eligible for definitive CRT were randomized (1:2) to Arm A (CRT: 70Gy/35F + cisplatin 100 mg/m2 Q3W on days 1,22,43 of RT) vs Arm B (durva IV 1500 mg, days -7, 22 of RT, followed by adjuvant durva for 6 doses). Primary objective was 3-year EFS in Arm B (efficacy if one-sided 90% CI lower bound [LB] >83%). Secondary objectives: QoL (MDADI, FACT-HN at baseline, end of RT, 3,6,12,24 and 36 mo), OS, safety, distant metastasis-free survival (DMFS) and locoregional control (LRC). Safety was assessed per CTCAE v5. The trial closed early based on emerging external efficacy data of IO in HN LA setting, enrolling 129 pts overall (80 of the planned 120 in Arm B) with approximately 80% power retained for the primary analysis. Results: 129 pts were randomized across 21 Canadian and European sites. Baseline characteristics were well balanced between arms. At the data cutoff (Sep 19, 2025), median follow-up time was 55.7 mo. In both arms, all pts received the planned RT schedule. In Arm A, the median number of cisplatin cycles was 2 (21% received <200m/m 2 and 79%≥ 200 mg/m 2 ). In arm B, all pts (100%) received durva concurrent to RT. 126 pts were eligible for efficacy analysis. The estimated 3-year EFS in Arm B was 80% (one-sided 90% CI: LB 73%); the prespecified efficacy criterion (LB >83%) was not met. The 3-year EFS in Arm A was 89%. The estimated 3-year OS rates were 92% in both arms. At 3 years, LRC were 97 and 91% in Arms A and B respectively. DMFS was 89% in Arm A and 86% in Arm B. Grade ≥ 3 adverse events any time during trial were similar between Arm B (69%) and Arm A (63%). QoL completion was 96% at baseline and 80%+ throughout; acute worsening during RT followed by gradual recovery (slower in arm B during adjuvant durva), with longer-term persistence of isolated issues (hearing loss, dry mouth) was similar to published experience for drug+RT regimens. Conclusions: Durva+RT did not improve 3-year EFS in the overall patient population of intermediate-risk HPV+ OPSCC. No new safety signal was observed. Specific toxicities varied by arm, but overall QoL experience, including swallowing, was similar between arms and with prior trials. Subgroup analysis, blood, tissue and microbiome-based correlates are ongoing. Clinical trial information: NCT03410615 .
Survival and pain treatment de-escalation of concurrent chemoradiotherapy combined with nimotuzumab and analgesics for patients with advanced head and neck cancer: A randomized, controlled clinical study.
e18001 Background: Patients with advanced head and neck cancer (HNC) have a poor prognosis. Pain is a disruptive complication of cancer, especially in HNC patients, and reduces the survival rate and quality of life. Anti-epidermal growth factor receptor (EGFR) antibody together with cyclooxygenase-2 reduces cancer pain in previous study. Nimotuzumab is a humanized monoclonal EGFR antibody with anti-tumor activity. We investigated the clinical effectiveness and observed pain palliation of nimotuzumab combined with concurrent chemoraditherapy (CCRT) and analgesics for patients with advanced HNC. Methods: In this open-label, randomized, controlled clinical study, the clinical stage with III-IVb HNSCC patients were randomized (1:1) to control group (analgesics plus CCRT) and study group (nimotuzumab plus analgesics and CCRT). Intensity-modulated radiation therapy was performed with a total dose of 66-70Gy (2Gy/F, 35F) for 6 consecutive weeks. Chemotherapy regimen was cisplatin at a dose of 30mg/m 2 /w for 6 weeks. Nimotuzumab was administered at a dose of 200mg weekly for 6 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), numerical rating scale (NRS), and safety. Results: In total, 194 patients were included in this study, 99 patients were assigned in study group and 95 in control group. The median follow-up was 39.0 month (95%CI: 37.4, NA) in study group and 35.1 month (95%CI: 29.9, NA) in control group. Compared to the control group, study group showed prolonged PFS (2-year PFS: 30.1% vs. 14.8%, P＜0.0001, mPFS: 16.2 month vs. 10.1 month), and OS (2-year OS: 58.2% vs. 24.7%, P＜0.0001, mOS: 29.8 month vs. 17.1 month). The addition of nimotuzumab significantly alleviates the cancer pain of patients in NRS score and de-escalation analgesic ladder (P<0.05), even 3 month after treatment (while without analgesic drug administration). Especially the day after first dosage, the NRS score decreased sharply in nimotuzumab group, also de-escalation the analgesic use. Graded 3-4 adverse events (AEs) in two groups exhibited no significant differences. No serious AEs and fatal outcomes occurred. Conclusions: The addition of nimotuzumab showed a promising survival profile and tolerable toxicity, also in coordination with cancer pain alleviation for advanced HNC patients. Clinical trial information: NCT06879691 .
Communication of tumor testing and molecular results to patients and caregivers in glioblastoma: A national survey.
e14041 Background: Tumor testing and molecular characterization are essential for personalized care in glioblastoma (GBM), informing treatment decisions and clinical trial eligibility. However, it is unclear whether patients and caregivers who are informed that testing occurred also report receiving explanations about tumor type and molecular findings. Methods: We conducted a cross-sectional analysis of a national, patient-led survey assessing GBM care experiences in the United States. Adult patients with GBM and caregivers responding on their behalf were included (n = 519). The primary endpoint was reported explanation of tumor types and mutations among respondents informed that tumor testing occurred; a secondary endpoint was reported communication regarding tumor tissue storage for future analysis. Cognitive recall risk was classified as elevated among respondents reporting neurologic symptoms associated with impaired recall (confusion, memory problems, language disturbance, or seizures) at diagnosis or, for current patients, at survey completion. Associations with age at diagnosis (<40, 40–64, ≥65) and treatment setting (NCI-designated vs non-NCI centers) were evaluated using chi-square or Fisher’s exact tests, as appropriate. Sensitivity analyses examined associations between “Not sure” responses, respondent type, and cognitive recall risk. Results: Among respondents informed that tumor testing occurred (n = 345 [20.6% patients, 79.4% caregivers]; 66.5% of all respondents), 77.1% reported that tumor types and mutations were explained, while 22.9% reported no explanation. Explanation rates varied by age at diagnosis (p = 0.008), decreasing with increasing age, and by treatment setting, with higher rates at NCI-designated versus non-NCI centers (80.8% vs 73.2%; p = 0.009). Communication regarding tissue storage varied more strongly by care setting; respondents treated at NCI-designated centers were more likely to report being informed (39.3% vs 22.1%; p < 0.001). A modest age-related difference was observed (p = 0.044), with tissue storage awareness highest among respondents aged <40 years (43.6%), compared with 40–64 years (29.2%) and ≥65 years (25.7%). Uncertainty (“Not sure”) regarding whether tumor testing occurred was not associated with respondent type or cognitive recall risk (both p > 0.20). Conclusions: Awareness that tumor testing occurred does not consistently translate into reported communication about tumor biology among patients with GBM and their caregivers. Communication gaps are more pronounced outside NCI-designated centers and among older patients and are not explained by recall limitations. These findings highlight a measurable gap in communication of molecular testing and tissue preservation processes and support efforts to improve communication, particularly in community oncology settings.
Hallmarks-of-cancer in stage II-III NSCLC treated with chemoradiotherapy (CRT).
e20052 Background: Stage II-III NSCLC adenocarcinoma (ADC) treated with definitive CRT is clinically heterogeneous. Post-CRT treatment decisions are seldom guided by integrated tumor biology. We tested if a Hallmarks-of-Cancer-based aggregation of routine panel NGS findings can generate biologically interpretable profiles to support translational stratification and therapeutic hypotheses. Osimertinib approval as consolidation for stage III EGFR-mutated NSCLC in 2024 made NGS the new standard-of-care (SOC) test. Methods: 45 stage II-III NSCLC-ADC with definitive CRT had targeted NGS using the QIAGEN Lung Cancer Multimodal Panel (DNA mutations/CNVs and fusion partners) on a NextSeq 2000 (Nextera XT, dual indexes, UMI chemistry). From the first 10 ADC the detected variants were mapped to 14 Hallmarks via a predefined gene-to-hallmark model and aggregated to case-level hallmark scores. Two scoring modes were evaluated: „clean“ (pathogenic (P)/likely pathogenic (LP), LP/P only; VUS weight = 0) and „all“ (LP/P + VUS; VUS weight = 0.25) as a sensitivity analysis. Unsupervised hierarchical clustering was performed on clean hallmark matrices. Results: We found 22 LP/P events across 12 genes. TP53 was most frequent (8/10), followed by KRAS (2/10); single cases carried EGFR, MET, KEAP1, ARID1A, SMARCA4, ATM, BRAF, NF1, RBM10 and APC alterations; one tumor had no LP/P variants. Hallmark profiling (clean) consistently highlighted a dominant „damage-response/senescence“ phenotype with high H10 (Senescent cells/SASP) in 8/10 (mean 16.0) and broad H11 (Genome instability) activity in 9/10 (mean 8.27), accompanied by H2 (growth suppressor evasion) and H3 (cell death resistance). Clustering separated (i) an 8/10 TP53-driven backbone cluster suggestive of shared CRT-relevant stress-adaptation biology, (ii) an LP/P-negative case, and (iii) one distinct outlier harboring ARID1A/SMARCA4 with KEAP1 alterations, characterized by prominent H13 (epigenetic reprogramming) and H9 (phenotypic plasticity) together with H8 (immune destruction avoided), H12 (tumor-promoting inflammation) and H7 (energetics). Including VUS („all“) preferentially increased immune/invasion/angiogenesis hallmarks (H8, H6, H5), indicating potentially actionable biology not captured by strict LP/P filtering. Results of further 35 identified ADC and clinical outcomes (ORR/PFS/OS) will also be shown. Conclusions: Hallmark-level aggregation of SOC panel NGS in CRT-treated stage II-III NSCLC yields translationally interpretable biological subgroups: a prevalent TP53/SASP-genome-instability stress-adaptation backbone and a distinct SWI/SNF-KEAP1 subgroup with epigenetic plasticity and immune-inflammatory features. This approach provides a pragmatic framework to prioritize post-CRT strategies and trial hypotheses (e.g., DDR-informed, epigenetic/immune-microenvironment-directed combinations) beyond single gene drivers.
APOBEC mutational signatures to predict immune checkpoint inhibitor benefit in TMB-low metastatic NSCLC independent of PD-L1 status.
3130 Background: Most metastatic non-small cell lung cancer (NSCLC) patients are tumor mutational burden (TMB)-low (<10 mut/Mb) and lack validated biomarkers to guide immune checkpoint inhibitor (ICI) use beyond PD-L1 expression. APOBEC mutagenesis, characterized by distinct mutational signatures, has been linked to ICI response in urothelial and head and neck cancers – but primarily in TMB-high tumors. Whether APOBEC activity predicts ICI benefit specifically in TMB-low NSCLC, independent of PD-L1 status, remains unclear. Methods: We analyzed a discovery cohort of 857 metastatic TMB-low NSCLC patients treated with ICI from the MSK-CHORD cohort. To distinguish predictive from prognostic effects, we examined 1,328 ICI-untreated TMB-low metastatic NSCLC patients as controls. Findings were validated in an independent cohort of 82 TMB-low, ICI-treated stage IV NSCLC patients using whole exome sequencing (WES). APOBEC positivity was determined using MESiCA, a validated machine-learning algorithm designed to detect mutational signatures from targeted gene panels with low mutation counts (≥4 mutations). Primary endpoints were overall survival (OS) and disease control rate (DCR) in the discovery cohort, and progression-free survival (PFS) and objective response rate (ORR) in the validation cohort. Multivariate Cox regression adjusted for PD-L1 status and age. Results: In the discovery cohort, APOBEC-positive (n=52, 6.1%) and APOBEC-negative (n=805) patients were balanced for sex (44% vs 46% male), histology (83% vs 79% adenocarcinoma), and PD-L1 status (40% vs 40%; all p>0.05); APOBEC-positive patients were younger (median 64 vs 69 years, p=0.002). The APOBEC-positive group demonstrated significantly improved OS (median 33.7 vs 17.4 months; HR=0.60; 95% CI, 0.42–0.85; p=0.004). The survival benefit was absent in ICI-untreated patients (HR=0.98; 95% CI, 0.76–1.26; p=0.85). Formal interaction testing confirmed that the APOBEC benefit was specific to ICI-treated patients (interaction HR=0.62; p=0.032). APOBEC-positive tumors demonstrated higher DCR at 180 days (21.4% vs 7.6%; OR=3.32; p=0.006). In multivariate analysis adjusting for PD-L1 and age, APOBEC remained independently predictive (HR=0.57; 95% CI, 0.40–0.81; p=0.002). In the validation cohort, APOBEC independently predicted superior PFS (HR=0.23; 95% CI, 0.05–0.94; p=0.020) after adjusting for PD-L1, with numerically higher ORR (55.6% vs 25.4%, p=0.068). Conclusions: APOBEC mutational signatures represent a robust, independently validated predictive biomarker for ICI response in TMB-low metastatic NSCLC. Unlike prior studies linking APOBEC predominantly to TMB-high tumors, we demonstrate clinical utility specifically in the TMB-low population, where predictive biomarkers are most needed. This biomarker could expand immunotherapy access for NSCLC patients.
Outcomes of pneumococcal disease in patients with B-cell malignancies: A retrospective cohort study.
e23110 Background: Streptococcus pneumoniae disproportionately affects adults with B-cell hematologic malignancies due to profound humoral immune dysfunction and B-cell–depleting therapies. Although ACIP recommends pneumococcal conjugate vaccination for all immunocompromised adults, guidance does not distinguish B-cell malignancies from other hematologic cancers. National data defining severe inpatient outcomes in this high-risk subgroup are limited. We evaluated outcomes of pneumococcal disease hospitalizations among adults with B-cell hematologic malignancies. Methods: We conducted a retrospective study of hospitalizations with a principal diagnosis of pneumococcal disease using in the HCUP all-payer database (2018–2021). The primary exposure was B-cell hematologic malignancy. Primary outcome was in-hospital mortality; key secondary outcomes were invasive mechanical ventilation (IMV), length of stay (LOS), and total hospital charges. Weighted multivariable logistic regression (odds ratios [OR], 95% confidence intervals [CI]) and linear regression (beta [B]) adjusted for demographics, payer, socioeconomic status, comorbidity burden, sepsis severity, and hospital factors were used to estimate effects. Results: Among an estimated 186,860 pneumococcal hospitalizations, B-cell hematologic malignancy was independently associated with higher odds of IMV (OR 1.87, 95% CI 1.73–2.02; p < 0.001) but not increased in-hospital mortality (OR 0.97, 95% CI 0.86–1.10; p = 0.629). B-cell malignancy was associated with longer LOS (B = 0.69 days; p < 0.001) and a marginal increase in cost (B = $4,729; p = 0.051). Acute illness severity dominated outcomes: ventilator use strongly predicted mortality (OR 8.18, 95% CI 7.80–8.57; p < 0.001), and sepsis/severe sepsis were major drivers of IMV and death (all p < 0.001). In secondary analyses, results were directionally consistent when expanding exposure to all hematologic malignancies (IMV OR 1.87; mortality OR 0.95). Conclusions: Adults with B-cell hematologic malignancies hospitalized for pneumococcal disease experienced significantly higher risk of invasive mechanical ventilation and longer hospital stays, without increased adjusted in-hospital mortality. These findings support prioritization and systematic delivery of pneumococcal conjugate vaccination strategies in B-cell malignancy populations to reduce severe respiratory morbidity and healthcare utilization. Adjusted association of B-Cell hematologic malignancy with inpatient outcomes. Outcome Adjusted Effect Estimate 95% CI p-value In-hospital mortality OR 0.97 0.86–1.10 0.629 Invasive mechanical ventilation OR 1.87 1.73–2.02 <0.001 Length of stay (days) B = +0.69 0.43–0.96 <0.001 Total hospital charges (USD) B = +4,729 −29 to 9,487 0.051
Survival outcomes between neoadjuvant and adjuvant chemo-immunotherapy in patients with stage II–III NSCLC undergoing surgical resection.
8060 Background: In patients with stage II–III NSCLC, perioperative systemic therapy is recommended; however, the optimal timing of chemo-immunotherapy relative to surgery remains an area of active investigation. The aim of this study was to compare overall survival outcomes between neoadjuvant and adjuvant chemo-immunotherapy in patients with stage II–III NSCLC undergoing surgical resection. Methods: We utilized the National Cancer Database (NCDB) and included patients with complete follow-up data, diagnosed between 2018 and 2023 with clinically staged IIA–IIIB NSCLC (cT1–cT4, cN0–cN2, cM0), who underwent definitive surgical resection, and received either neoadjuvant or adjuvant chemo-immunotherapy. Kaplan–Meier analysis and propensity score–adjusted Cox proportional hazards models were used to assess survival outcomes. Results: A total of 2,815 patients met the inclusion criteria, including 1,521 (54%) males, with a median age of 66 years. Of these, 1,186 (42%) patients received neoadjuvant therapy and 1,629 (58%) received adjuvant therapy. Median overall survival (OS) was not reached in the neoadjuvant group, compared with 79.4 months (95% CI, 68.1–90.7, p < 0.001) in the adjuvant group (Table 1). On propensity score–adjusted Cox regression, neoadjuvant therapy was associated with a significant OS advantage compared with adjuvant therapy (HR 0.71; 95% CI, 0.58–0.87; p < 0.001). Neoadjuvant therapy was associated with improved OS among patients with baseline cN2 disease (HR 0.64; 95% CI, 0.45–0.91; p = 0.012). No statistically significant difference in OS was observed among patients with cT3 or cT4 disease (HR 0.95; 95% CI, 0.66–1.36; p = 0.759) and HR 0.67; (95% CI, 0.45–1.01; p = 0.053), respectively. Conclusions: In patients with stage II–III NSCLC undergoing surgical resection, neoadjuvant chemo-immunotherapy was associated with improved overall survival compared with adjuvant therapy, particularly among those with a higher nodal or regional tumor burden at presentation. Median overall survival and hazard ratios for neoadjuvant versus adjuvant chemo-immunotherapy in stage II–III NSCLC. Neoadjuvant Median OS (months) Adjuvant Median OS (months) Hazard Ratio (HR) 95% CI p-value Overall cohort NR 79.4 (68.1–90.7) 0.71 0.58–0.87 <0.001 cN2 NR 62.6 (45.4–79.8) 0.64 0.45–0.91 0.012 cT3 NR 76.3 (62.4–90.1) 0.95 0.66–1.36 0.759 cT4 71.0 (62.7 – 79.3) 56.1 (37.6- 74.5) 0.67 0.45–1.01 0.053
Epidemiological trends and burden of gastric cancer mortality in South Asia: A retrospective analysis from 1990 to 2023 with advanced machine learning (ARIMA) forecasting to 2050.
e15656 Background: Gastric cancer remains a major cause of cancer-related mortality in South Asia, with substantial heterogeneity across countries and sexes. Understanding long-term mortality trends and future projections is essential for guiding targeted prevention and control strategies in the region. Methods: We analyzed age-standardized mortality rates (ASMRs) for gastric cancer in South Asian countries from 1990 to 2023, using IHME GBD 2023 data. Temporal trends were assessed using estimated annual percentage change (EAPC) with 95% confidence intervals (CIs), stratified by sex. ARIMA forecasting models were applied to project mortality trends through 2050, with uncertainty quantified using prediction intervals. Results: From 1990 to 2023, gastric cancer ASMRs in South Asia showed a significant overall decline for both sexes combined (EAPC −0.84; 95% CI −0.96 to −0.71). Declines were comparable between females (EAPC −0.84; 95% CI −0.95 to −0.73) and males (EAPC −0.74; 95% CI −0.89 to −0.58), although mortality rates consistently remained higher among males. Nepal demonstrated the steepest decline across the region (both sexes EAPC −1.42), followed by India (−0.96), Bhutan (−0.69), and Pakistan (−0.43). Bangladesh exhibited a heterogeneous pattern, with modest overall reductions (EAPC −0.26). While female mortality declined significantly (EAPC −0.77; 95% CI −1.02 to −0.52), male mortality remained near stable (EAPC 0.07; 95% CI −0.01 to 0.16). Historically, ASMRs declined steadily from the early 1990s through the mid-2010s, followed by plateaus and transient increases after 2020, particularly among males. Forecasts to 2050 suggest continued regional declines driven by India and Nepal; however, Bangladesh, especially among males, is projected to experience persistent or rising mortality. Conclusions: Gastric cancer mortality in South Asia has declined substantially over the past three decades, but progress remains uneven. Stagnant mortality among Bangladeshi males and projected future increases highlight critical gaps in prevention and early detection. Targeted, sex-specific interventions will be essential to sustain and accelerate mortality reductions across the region. Location Sex EAPC Lower 95%CI Upper 95%CI Bangladesh Both -0.26 -0.40 -0.11 Bangladesh Female -0.77 -1.02 -0.52 Bangladesh Male 0.07 -0.01 0.16 Bhutan Both -0.69 -0.84 -0.53 Bhutan Female -0.65 -0.81 -0.49 Bhutan Male -0.72 -0.87 -0.57 India Both -0.96 -1.11 -0.82 India Female -0.89 -1.02 -0.77 India Male -0.90 -1.08 -0.73 Nepal Both -1.42 -1.69 -1.16 Nepal Female -1.48 -1.71 -1.24 Nepal Male -1.31 -1.60 -1.02 Pakistan Both -0.43 -0.53 -0.32 Pakistan Female -0.30 -0.44 -0.17 Pakistan Male -0.60 -0.75 -0.45 South Asia Both -0.84 -0.96 -0.71 South Asia Female -0.84 -0.95 -0.73 South Asia Male -0.74 -0.89 -0.58