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Prognostic implications of HPV-related nasopharyngeal carcinoma in non-endemic regions: A meta-analysis.
e18147 Background: The cancerogenic role of the Epstein Barr Virus (EBV) is well established in endemic non-keratinizing nasopharyngeal carcinoma (NPC). Nearly 10% of non-endemic (NE) NPCs are keratinizing squamous cell carcinomas, scarcely associated with EBV infection and more strongly linked to tobacco exposure. Some EBV-ve NPCs are HPV+ve, with limited data of its prognostic role. Methods: We performed a meta-analysis (MA) from published studies that included NE EBV-ve/HPV+ve NPC with available data regarding overall survival (OS) and a direct comparison with NPC’s subgroups. Hazard ratios and 95% confidence intervals for OS were extracted from each study and harmonized to a common reference group. Pooled estimates were obtained using random-effects MA, and between-study heterogeneity was quantified using the I² statistic . Results: We retrieved 5 studies including a total of 1084 subjects. In four studies the EBV+ve/HPV-ve NPCs (group A) were compared to EBV-ve/HPV+ve NPCs (group B) and to EBV-ve/HPV-ve NPCs (group C). Group B and C comparison was available in two studies. Group C was associated with significantly worse OS compared to group A in a random-effects meta-analysis (pooled HR = 2.30, 95% CI 1.51–3.52; I²=0%, p<0.001). Group C showed also a significantly worse OS compared to group B (pooled HR = 2.08, 95% CI 1.26–3.44; p=0.004), with no evidence of between-study heterogeneity (I²=0%). Finally, the comparison between group A and B showed a positive trend in favour of EBV+ve NPC, with no statistical significance (pooled HR = 1.41, 95% CI 0.87–2.28, I²=0%, p=0.16), indicating comparable survival outcomes between virus-related NPCs. In table 1 are summarized trials characteristics and the pooled analyses. Conclusions: Our analysis indicates that in NE EBV-ve NPCs a distinct HPV+ve subpopulation display a better OS relative to HPV-ve and a similar OS relative to EBV+ve, supporting HPV testing in all EBV-ve NPCs. Prospective studies are warranted to further validate these findings. Studies included in the Meta-analysis, respective hazard-ratio and p value and pooled analyses. Study Total n° of patients pvalue Outcome Reference Contrast Hazard Ratio (HR) 95% CI Stenmark et al 62 0.390.39 OS AA BC 1.831.26 [0.71, 4.72][0.37, 4.25] Wu et al 78 0.110.0030.414 OS AAB BCC 2.413.751.55 [0.82, 7.11][1.59, 8.84][0.54, 4.45] Ruuskanen et al 150 0.0050.03 OS AB CC 2.272.22 [1.28, 4.01][1.06, 4.76] Huang et al 451 0,73 OS A B 0.85 [0.33, 2.17] Verma et al 343 0.640.61 OS AA BC 1.231.46 [0.51, 2.99][0.33, 4.39] Pooled Analyses Groups Comparison: A vs C Pooled HR: 2.30 95% CI 1.51, 3.52 p<0.001 Groups Comparison: B vs C Pooled HR:2.08 95% CI 1.26, 3.44 p=0.004 Groups Comparison: A vs B Pooled HR: 1.41 95% CI 0.87, 2.28 p=0.16 Legend:A: EBV+ve/HPV-ve. B: EBV-ve/HPV+ve. C: EBV-ve/HPV-ve.
Treatment-interrupting hospitalization as an acute oncologic toxicity in solid tumors.
e23204 Background: Treatment-interrupting hospitalization (TIH) refers to unplanned admissions disrupting systemic cancer therapy. TIH reflects cumulative impacts of treatment toxicity, disease burden, frailty, and healthcare factors, associated with increased mortality, prolonged hospitalization, functional decline, and treatment disruption. Methods: The National Inpatient Sample (NIS), 2016–2022, was analyzed to construct a solid tumor cohort (ICD-10 malignant neoplasms C00–C80), excluding hematologic malignancies (C81–C96) and palliative encounters (Z51.5). The analytic cohort included 3,046,500 unweighted hospitalizations. TIH (core) was defined by any of the following: LOS ≥7 days, mechanical ventilation, shock (R57), sepsis or septic shock (A40/A41/R65.2), neutropenia (D70), major organ toxicities (AKI N17, acute respiratory failure J96, pneumonitis or ARDS J70/J80, venous thromboembolism I26/I80/I82), or frailty syndromes (malnutrition E43/E44/E46, cachexia R64, dysphagia R13*, pressure ulcer L89*, falls W0/W1/R29.6/Z91.81). A prespecified strict definition required LOS ≥10 days or ICU, mechanical ventilation, shock, sepsis, or neutropenia. Survey-weighted analyses used NIS weights, strata, and primary sampling units. Adjusted models included age, sex, year, race, payer, ZIP-code income quartile, elective admission, weekend admission, hospital region, number of beds, and teaching status. Results: TIH prevalence was 59.3% (95% CI 59.1–59.5); TIH (strict) was 27.0% (95% CI 26.8–27.1). Compared with non-TIH admissions, TIH admissions had higher crude mortality (4.32% [95% CI 4.26–4.37] vs 0.316% [95% CI 0.305–0.328]), longer LOS (7.80 days [95% CI 7.77–7.83] vs 2.85 days [95% CI 2.84–2.85]), and higher costs ($26,958 [95% CI $26,376–$27,540] vs $16,466 [95% CI $16,115–$16,817]). TIH admissions more often required airway escalation (5.84% [95% CI 5.79–5.90] vs 0.149% [95% CI 0.138–0.161]) and non-home discharge (54.38% [95% CI 54.14–54.63] vs 23.44% [95% CI 23.20–23.69]). In adjusted models, TIH (core) was strongly associated with inpatient mortality (aOR 13.58, 95% CI 12.99–14.20), airway escalation (aOR 50.19, 95% CI 46.35–54.35), increased LOS (+5.28 days, 95% CI 5.25–5.31), and higher costs (log-cost coefficient 0.709, 95% CI 0.701–0.716; approximately 2.03-fold increase). Sensitivity analyses using TIH (strict) yielded consistent associations with mortality (aOR 8.52, 95% CI 8.34–8.70), airway escalation (aOR 36.46, 95% CI 34.76–38.24), and LOS (+7.78 days, 95% CI 7.73–7.84). Conclusions: Treatment-interrupting hospitalizations are common among solid tumor admissions and identify hospitalizations with higher mortality, escalation of care, cost, and non-home discharge. Conceptualizing TIH as an acute oncologic toxicity provides a practical, reproducible framework to systematically identify severe inpatient events disrupting systemic therapy.
The impact of various radiation therapy options on plasminogen activation markers in the blood of patients with metastatic brain lesions.
2025 Background: Metastatic brain disease (MBD) is found in almost a third of patients with malignant neoplasms and is characterized by a high mortality rate. The role of the fibrinolytic system has been demonstrated in neoplasms of various locations, while tissue plasminogen activator (t-PA) is studied less frequently than urokinase activator. The aim of this study was to investigate the level and activity of t-PA in the blood of patients with MBD receiving different radiotherapeutic treatments. Methods: Plasma from 38 patients of both sexes, aged 59.9 ± 8.9 years, with brain metastases confirmed by magnetic resonance imaging (MRI), was analyzed using enzyme-linked immunosorbent assay (ELISA) to determine t-PA activity and levels, calculate the ratio between them, and determine parameters of type 1 plasminogen activator inhibitor (PAI-1) and the receptor for both plasminogen activators (uPAR). The results were compared with data from 18 individuals without cancer (a donor group). Three groups were formed based on the treatment regimens: Control — stereotactic radiotherapy at the site of the resected metastasis with a single fraction dose (SFD) of 6 Gy up to a total dose of 30 Gy; Main Group No. 1 — after a preoperative radiosurgery session with an SFD of 10–15 Gy, the metastatic lesion was removed 24 hours later; Main Group No. 2 — staged radiosurgery (SRS) was performed in 3 sessions with an SFD of 10 Gy at 14-day intervals (total dose of 30 Gy). Results: Before treatment, a 2.1-fold increase in t-PA activity was observed in the blood of patients with MBD. This, together with a 3.6-fold reduction in t-PA content, led to a 10-fold increase in their ratio (p ≤ 0.0002). Meanwhile, urokinase activator activity did not change. In the control group, t-PA activity remained elevated three days after surgery and did not differ from donor levels one month later, while t-PA levels remained reduced. In both main groups, elevated t-PA activity relative to donors was observed throughout the entire observation period, and after one month, it was 2.6 times higher than in the control group (p ≤ 0.001). Only patients receiving SRS were characterized by an increase in the initially reduced t-PA content, with a change toward normalization of the t-PA activity-to-content ratio. This was accompanied by an increase in the activity of inhibitor PAI-1 and receptor uPAR to donor levels. Conclusions: The revealed dynamics of t-PA and PAI-1 parameters in SRS compared with other types of radiation therapy may be one of the factors contributing to the greater positive clinical efficacy of this developed method of staged radiotherapy in the treatment of metastatic brain tumors.
The role of rhamnose derived from gut microbiome in modulating the efficacy of non-small cell lung cancer immunotherapy.
e14586 Background: In recent years, the relationship between gut microbiota and metabolites and immunotherapy for non-small cell lung cancer （NSCLC） has gradually become a research hotspot. Rhamnose is a monosaccharide that can be secreted by the gut microbiome and has certain potential in regulating immune responses. The mechanism by which Rhamnose regulates the efficacy of immunotherapy for NSCLC is not yet clear. The aim of this study is to explore the mechanism by which gut microbiome metabolite rhamnose regulates the efficacy of immunotherapy for non-small cell lung cancer, providing new ideas for improving the efficacy of immunotherapy for non-small cell lung cancer. Methods: According to the progression free survival (PFS) of NSCLC patients after immunotherapy, they were divided into a response group (PFS > 6 months, R group) and a non-response group (PFS ≤ 6 months, NR group). Baseline fecal samples were collected from patients for non-targeted metabolomics sequencing to screen for rhamnose. Using a mouse lung cancer model, mice were divided into a control group, a rhamnose group, an anti-PD-1 treatment group, and a combination therapy group (rhamnose +anti-PD-1). Observe the changes in tumor volume in different groups of mice. Flow cytometry and immunohistochemical were used to detect changes in tumor infiltrating CD8 + T cells in different groups of mice. ELISA was used to detect the expression levels of IFN - γ and Granzyme B in the plasma of different groups of mice. Results: Non-targeted metabolomics sequencing found that compared with the NR group, the R group had significantly increased levels of rhamnose. In vivo studies on mice showed that compared to the anti-PD-1 monotherapy group, the combination treatment group showed a significant slowdown in tumor volume growth. The results of flow cytometry and immunohistochemical showed that compared with the anti-PD-1 monotherapy group, the infiltration of CD8 + T cells in tumor tissues increased in the combination treatment group. According to the ELISA results, the proportion of IFN - γ and Granzyme B in peripheral blood of the combined treatment group also increased, indicating the regulatory effect of rhamnose on systemic immune response. Conclusions: The efficacy of NSCLC immunotherapy may be related to gut microbiome metabolite rhamnose. Rhamnose enhances the function of CD8 + T cells by increasing tumor infiltration and raising the levels of cytokine IFN–γ and Granzyme B.
Hepatic arterial infusion chemotherapy combined with immunotherapy for unresectable intrahepatic cholangiocarcinoma: A single-arm, open-label, prospective clinical trial.
2600 Background: In recent years, immune checkpoint inhibitors (ICIs) have demonstrated substantial clinical advances in the treatment of intrahepatic cholangiocarcinoma (ICC). However, the efficacy of first-line systemic chemotherapy remains suboptimal for patients with unresectable ICC. Hepatic arterial infusion chemotherapy (HAIC) can markedly elevate local drug exposure, enhance tumor cytotoxicity, and minimize systemic adverse effects. Whether the combination of HAIC and immunotherapy confers a clinical benefit for patients with unresectable ICC remains an urgent clinical issue to be addressed. Methods: This is a single-arm, open-label, prospective clinical trial designed to evaluate the efficacy and safety of HAIC combined with ICIs in the treatment of patients with unresectable ICC. The HAIC regimen consists of gemcitabine plus cisplatin (GC-HAIC), while programmed death-1 (PD-1) inhibitors are administered for immunotherapy, with either camrelizumab or sintilizumab chosen on a patient clinical characteristics basis. The trial was planned to enroll 30 participants. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). Safety was assessed through the monitoring and grading of adverse events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Results: From August 2022 to January 2025, a total of 31 patients with unresectable ICC were enrolled and received the protocol-defined treatment. The ORR was 41.9% according to RECIST 1.1 criteria, while the ORR assessed per mRECIST criteria was 71%. The median follow-up time was 22.0 months (95% CI, 17.9–26.7 months). The median OS was 20.0 months (95% CI, 15.7–28.6 months), and the median PFS was 12.3 months (95% CI, 10.9–21.3 months). The DCR reached 93.5%. Treatment-related AEs of any grade occurred in 83.9% of patients, whereas grade 3 or 4 AEs were observed in only 16.1% of participants. Conclusions: This study evaluated the efficacy and safety of GC-HAIC combined with anti-PD-1 immunotherapy in the treatment of patients with unresectable ICC. The results demonstrated that this regimen exhibited promising efficacy, with manageable adverse events and complications. Additionally, these results also offer a potential novel first-line treatment option for this patient population. Based on the results of this study, future phase III clinical trails are warranted to validate the outcomes. Clinical trial information: ChiCTR2500112123. Tumor response. Efficacy RECIST 1.1 mRECIST % N % N CR 0 0 3 9.7 PR 13 41.9 19 61.3 SD 16 52.6 7 22.6 PD 2 6.5 2 6.5 ORR 13 41.9 22 71.0 DCR 29 93.5 29 93.5 CR, Complete response; PR, Partial response; SD, Stable disease; PD, Progressive disease; ORR, Objective response rate; DCR, Disease control rate.
Clinical and translational study of YBX1 as a biomarker and therapeutic target in bone metastasis of non–small cell lung cancer.
e20574 Background: Bone metastasis in non-small cell lung cancer (NSCLC) is associated with poor prognosis and immunosuppression, yet reliable biomarkers and therapeutic targets are lacking. YBX1, a transcription factor, may play a key role in bone metastasis progression. Methods: This study included 180 NSCLC patients without initial metastasis (2018–2020) and 80 patients with bone metastasis at diagnosis. YBX1 expression was evaluated by immunohistochemistry. Functional experiments were conducted using high-metastatic NSCLC cell lines and mouse models. A small-molecule library was screened to identify YBX1-targeting compounds. Statistical analysis employed Kaplan–Meier, Cox regression, and t-tests. Results: Among the 180 follow-up patients, 38 developed bone metastasis. YBX1 expression was significantly higher in bone metastasis cases (p<0.001) and independently predicted metastasis risk (HR=2.91, 95% CI 1.45–5.71, p<0.01). High YBX1 correlated with elevated serum IL-6 and CCL5 and poorer survival. Mechanistically, YBX1 promoted osteoclast activation and Treg recruitment via IL-6/CCL5. The compound Icaritin enhanced YBX1 O-GlcNAcylation at T271, promoted its mitochondrial translocation and degradation, and suppressed bone metastasis in mouse models. Combining Icaritin with anti-PD-1 therapy enhanced CD8⁺ T-cell infiltration and reduced Treg accumulation. Conclusions: YBX1 is a promising prognostic biomarker and therapeutic target in NSCLC bone metastasis. Its upregulation drives immunosuppression and osteolytic progression, while targeting YBX1 glycosylation with Icaritin inhibits metastasis and synergizes with immunotherapy.
Genomic and immunogenomic characteristics of <i>KRAS</i> -altered ovarian cancer in a Chinese real-world cohort: Implications for precision therapy in the era of KRAS inhibitors.
e17589 Background: With the recent approval of the KRAS pathway–targeted combination of avutometinib and defactinib for low-grade serous ovarian carcinoma, understanding the prevalence, genomic characteristics, and immunogenomic features of KRAS-altered ovarian cancer has become increasingly important. However, comprehensive data describing KRAS mutation patterns in Chinese ovarian cancer patients remain limited. This study aimed to characterize KRAS alterations and their associated genomic and immune-related features in a real-world Chinese ovarian cancer cohort to inform future precision treatment strategies. Methods: Next-generation sequencing (NGS) data from 625 ovarian cancers were analyzed for KRAS alterations, with immunogenomic features compared between KRAS-altered and wildtype tumors and across histological subtypes. Results: KRAS alterations were identified in 8.6% (54/625) of patients, including SNVs in 6.1% (38/625) and CNVs in 2.6% (16/625). No germline KRAS variants were detected. Most SNVs occurred in exon 2, with hotspot mutations at codons 12 and 13, consistent with classical activating KRAS variants. Patients with KRAS alterations were significantly younger than KRAS-wildtype patients (P = 0.002). The most frequent co-altered genes in KRAS-altered tumors were TP53 (57.4%) and PIK3CA (27.8%), suggesting concurrent dysregulation of cell-cycle and PI3K signaling pathways. Histology-specific analysis revealed significant enrichment of KRAS alterations in clear cell carcinoma (20.0%, 4/20) and mucinous carcinoma/adenocarcinoma subtypes (6.1%, 2/33), highlighting potential subtype-specific therapeutic opportunities. Immunogenomic comparisons showed that HRD positivity was significantly lower in KRAS-altered tumors than in KRAS-wildtype tumors (24.1% vs 63.6%, P < 0.001), indicating limited overlap between KRAS-driven oncogenesis and homologous recombination deficiency. No MSI-high tumors were observed in the KRAS-altered group (0% vs 1.2%, P = 1.00). Median TMB was similar between KRAS-altered and wildtype tumors (5.03 vs 4.47 mut/Mb, P = 0.84), suggesting no apparent immunogenic advantage associated with KRAS alterations in ovarian cancer. Conclusions: KRAS alterations are less frequent in Chinese ovarian cancer and lack favorable immunogenomic features, suggesting limited benefit from immunotherapy combinations. However, their enrichment in clear cell carcinoma indicates a histology-specific opportunity for KRAS-targeted therapy. These findings provide a reference for the application in the treatment of ovarian cancer, and also highlight the necessity of further exploration of more genetic characteristics of ovarian cancer.
Genomic and transcriptomic correlates of HER3 expression in prostate cancer.
3142 Background: HER3 ( ERBB3 ) is a key receptor in prostate cancer (PC) that signals via HER3 heterodimerization to promote PI3K-AKT-mediated survival and adaptive resistance in castration-sensitive (CSPC) and castration-resistant prostate cancer (CRPC). Despite its biological relevance, the clinical and genomic significance of HER3 RNA expression remains poorly defined. We therefore performed a comprehensive multi-omic analysis to evaluate the prognostic relevance of HER3 RNA in PC. Methods: DNA (592-gene or whole exome) and RNA (whole transcriptome) sequencing were performed on prostate tumor samples (n=19,238) submitted to Caris Life Sciences. HER3 expression was quantified as transcripts per million (TPM) and stratified into high (HER3-H) and low (HER3-L) groups defined by the top and bottom quartiles, respectively. CRPC was defined as ≥3 months of androgen deprivation therapy before tissue collection. Real-world overall survival (rwOS) was obtained from insurance claims data and calculated from biopsy to last contact. Tumor microenvironment (TME) cell fractions were estimated by RNA deconvolution using quanTIseq. Group comparisons were conducted using Mann–Whitney U and chi-square tests as appropriate. Survival outcomes were evaluated using Cox proportional hazards models and log-rank testing, with false discovery rate correction for multiple comparisons. Results: Across genitourinary malignancies, PC demonstrated highest median HER3 RNA expression (107.04 TPM). Within PC, HER3 expression varied by tumor site and race, with higher median levels in primary tumors compared to metastatic sites (116.5 vs 86.22 T PM, p<0.0001), and in tumors from Black patients compared with White patients (115.3 TPM v 103.3 TPM, p<0.0001). Prognostic associations differed by tumor source and castrate status: HER3-H expression was associated with improved rwOS in metastatic tumors (32.0 vs. 23.3 months, HR 0.72, p < 0.00001), and in CRPC (29.3 vs. 21.3 months; HR 0.84; p < 0.001), but not in primary tumors or CSPC. Immune profiling revealed that HER3-high tumors exhibited significantly reduced inferred infiltration of Tregs, neutrophils, macrophages, and NK cells (q < 0.05), while PD-L1 positivity and TMB-high status were not significantly associated with HER3 expression. Genomic analysis revealed enrichment of FOXA1 and SPOP alterations (q<0.05) in HER3-H tumors, whereas HER3-L tumors were enriched for TP53 , RB1 , AR , CDK12 , and APC ( q<0.05). On multivariable analysis, HER3-H status remained independently associated with improved rwOS in CRPC. Conclusions: HER3 RNA expression defines biologically and clinically distinct subsets of PC, with HER3-high tumors exhibiting luminal, androgen receptor–dependent biology, an immune-cold phenotype, and improved survival in metastatic disease and CRPC, supporting HER3 as a tumor-intrinsic therapeutic target and rationale for HER3-directed therapy.
Sigvotatug vedotin (SV), an investigational integrin beta-6 (IB6)─directed antibody-drug conjugate (ADC), plus pembrolizumab: Updated results from the phase 1 study (SGNB6A-001).
8522 Background: IB6 is overexpressed in many tumors, such as non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC). SV, an IB6-directed ADC, demonstrated encouraging antitumor activity and manageable safety as monotherapy or in combination with pembrolizumab (SV+P) in advanced NSCLC (aNSCLC) in the ongoing phase 1 SGNB6A-001 study. We report updated results for SV+P. Methods: SGNB6A-001 (NCT04389632) is an open-label, multicenter, dose-escalation and -expansion study evaluating safety, pharmacokinetics, and antitumor activity of SV. SV+P is being evaluated in safety and expansion cohorts of treatment-naive locally advanced, unresectable, or metastatic NSCLC across PD-L1 scores and HNSCC CPS ≥1. Additional cohorts currently enrolling are not included in this analysis. We describe patients (pts) who received SV 1.8 mg/kg AiBW (adjusted ideal body weight) IV Q2W and P 400 mg IV Q6W. Primary endpoint is safety; secondary endpoints include efficacy, such as confirmed objective response rate (cORR) per RECIST v1.1 by investigator. Results: 71 pts across cohorts received ≥1 SV+P dose (37 aNSCLC, 33 HNSCC, 1 esophageal cancer). As of Sep 30, 2025, 34 pts were on treatment. Overall, any-grade (Gr) and Gr ≥3 treatment-emergent adverse events (TEAEs) occurred in 96% and 59% of pts, respectively; treatment-related any-Gr and Gr ≥3 TEAEs occurred in 85% and 44% of pts, respectively. Most common TEAEs ( > 30%) were alopecia, decreased appetite, fatigue, and nausea. In the expansion cohort, 35 pts with aNSCLC were treated, with median follow-up of 10.6 mo (95% CI, 7.6-11.9). In the efficacy-evaluable pts, cORR was 50% in both the PD-L1 TPS < 1% (n = 10) and ≥1% (n = 18) subgroups, with 1 additional partial response (PR) pending confirmation in the PD-L1 TPS ≥1% subgroup (Table). In 5 pts with PD-L1 TPS ≥50%, cORR was 80%, with 1 additional PR pending confirmation. Regardless of TPS, cORR was numerically higher in pts with nonsquamous (n = 19 [53%]) vs squamous (n = 9 [44%]) histology. Conclusions: SV+P continued to show manageable safety and encouraging antitumor activity in treatment-naive NSCLC across PD-L1 TPS and histologies. This supports the ongoing phase 3 SigVie-003 study (NCT06758401) of SV+P vs P for treatment-naive aNSCLC with PD-L1 TPS ≥50% as well as further investigation in the enrolling phase 1 cohorts and future studies. Clinical trial information: NCT04389632 . PD-L1 TPS <1% (n=10) PD-L1 TPS ≥1% (n=18) NSQ(n=19) SQ(n=9) cORR (95% CI), % 50(19 - 81) 50(26 - 74) 53(29 - 76) 44(14 - 79) BOR, % CR 0 6 5 0 PR 50 44 47 44 SD 40 44 42 44 NE/no assessment 10 6 5 11 ORR (95% CI), % 50(19 - 81) 61(36 - 83) 63(38 - 84) 44(14 - 79) DCR (95% CI), % 90(56 - 100) 94(73 - 100) 95(74 - 100) 89(52 - 100) mDOR (95% CI), mo NR(2.9 - NR) 8.1(4.2 - NR) 8.1(2.9 - NR) NR(4.2 - NR)
Four decades of population-based cancer incidence trends in Costa Rica: Implications for cancer surveillance in Central America.
e22551 Background: Reliable population-based cancer incidence data are essential for guiding cancer control strategies and evaluating long-term epidemiologic transitions. In Central America (Guatemala, Honduras, El Salvador, Costa Rica, Nicaragua, and Panama), national cancer burden estimates are largely derived from modeled data, and continuous registry-based incidence trends remain scarce. Costa Rica is the only Central American country with sustained representation in the Cancer Incidence in Five Continents (CI5plus) database, providing a unique opportunity to examine long-term cancer incidence patterns in the region. Methods: We analyzed population-based cancer incidence data from the CI5plus database for Costa Rica from 1982 to 2016. Annual crude incidence rates per 100,000 person-years were calculated by sex for all cancers excluding non-melanoma skin cancer and for major cancer sites. Temporal trends were assessed using Joinpoint-ready annual rate tables, enabling estimation of annual percent change (APC) and evaluation of long-term trend patterns. Analyses were stratified by sex and cancer type. Results: Over the 35-year study period, overall cancer incidence in Costa Rica demonstrated heterogeneous trends by sex and cancer site, including periods of increase, stabilization, and divergence between men and women. Prostate, stomach, lung, colorectal, breast, cervical, and liver cancers accounted for the majority of cases. Notably, stomach cancer—historically one of the most common malignancies—showed a substantial and sustained long-term decline in incidence (APC approximately −3% to −4% annually), particularly among men, contrasting with increasing or plateauing trends observed for prostate and colorectal cancers. This pattern is consistent with a true epidemiologic transition related to long-term changes in infection prevalence and living conditions rather than screening-related effects. Costa Rica remained the only Central American country with continuous CI5plus-quality incidence data throughout the study period. Conclusions: Costa Rica provides the sole long-term, high-quality population-based cancer incidence trends in Central America spanning more than three decades. The observed site-specific patterns, including the pronounced decline in stomach cancer, underscore the value of sustained cancer surveillance for identifying epidemiologic transitions. The absence of comparable CI5plus registries in neighboring countries highlights an urgent need to invest in high-quality, population-based cancer registries across Central America to support evidence-based, equitable cancer control and global oncology research.
Barriers and facilitators to implementation of evidence-based depression and distress treatment in adult oncology: A systematic review.
e13588 Background: Depression and psychological distress are common among cancer patients and are associated with increased mortality, yet uptake of evidence-based treatments remains low. While prior studies describe barriers to care, no systematic review has synthesized determinants using a structured implementation science framework. We identified barriers and facilitators to uptake and continuation of evidence-based depression/distress treatment in adult oncology patients and mapped them to Consolidated Framework for Implementation Research (CFIR) 2.0 constructs. Methods: We conducted a systematic review with a protocol registered on Open Science Framework. Searches of PubMed/MEDLINE, Embase, APA PsycINFO, Web of Science, and Cochrane identified qualitative and mixed-methods studies examining evidence-based depression/distress treatment in adult cancer patients. Extracted barriers and facilitators were mapped to CFIR 2.0 constructs. Results: The search yielded 7275 unique citations; 36 studies met inclusion criteria (n = 3777 participants). 14 papers elicited patient perspectives, 15 focused on healthcare professionals (HCPs), and 7 included patients, carers, and HCPs. 20 papers reported general barriers and facilitators to psychosocial support, and 16 focused on specific interventions (n = 8 for psychotherapy; n = 5 for collaborative care; n = 1 for antidepressants; n = 1 for support groups; and n = 1 for exercise); n = 5 used telehealth formats. Preliminary mapping identified prominent themes in the Individuals, Innovation, and Inner Setting domains. Among patients, barriers reflected reduced Capability (cancer-related fatigue, cognitive burden), limited Opportunity (competing treatment demands, time constraints), and variable Motivation (emotional avoidance, stigma). Facilitators included perceived need, readiness to engage, and belief in treatment benefit. Within the Innovation domain, barriers aligned with Complexity and Design, including usability challenges and time/administrative demands, whereas clear module progression, structured exercises, and reminders facilitated engagement. Within the Inner Setting, limited personnel and training hindered delivery, while embedded psychosocial services in oncology workflows and clinician endorsement and referral promoted uptake. Broader policy-level factors were relatively less represented. Conclusions: Successful implementation of depression and distress treatment in adult oncology patients depends on patient-level readiness, intervention design, and organizational context. Targeted strategies that reduce cognitive and logistical burden, improve usability, and integrate mental health services into oncology practice may improve uptake and engagement. Ongoing analysis will clarify multilevel determinants to inform implementation of psychosocial care.
The global burden of thyroid cancer from 1990 to 2023, with forecasts to 2050.
e22611 Background: Thyroid cancer is an important contributor to global health burden. Comprehensive and comparative estimation of thyroid cancer burden can inform policy decisions and public health interventions to reduce incidence, morbidity, and mortality. This study provides thyroid cancer estimates from 1990 to 2023, with forecasts to 2050. Methods: Using estimation methods from the Global Burden of Diseases, Injuries, and Risk Factors Study 2023 (GBD 2023) we estimated thyroid cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability adjusted life-years (DALYs). YLLs were calculated using life expectancy estimates. Prevalence and YLDs were calculated from expected survival, disease sequelae, and disability weights. DALYs were the sum of YLLs and YLDs. Results are presented with 95% Uncertainty Intervals (95% UI). Results: Globally in 2023 there were an estimated 304,000 (95% UI: 221,000 – 386,000) thyroid cancer cases and 52,200 (44,700 – 61,500) deaths, contributing to 1,560,000 (1,310,000 – 1,870,000) DALYs. Thyroid cancer burden was substantially higher in females than males, with 983,000 (760,000 – 1,250,000) and 577,000 (478,000 – 742,000) DALYs, respectively. From 1990 to 2023, global age-standardized rates for both sexes combined increased by 50.5% (5.2 – 119.8%) for incidence but remained stable for mortality (-4.0% [-18.9 – 16.3%]) and DALYs (4.3% [-13.6 – 30.3%]). These trends varied by World Bank Income Group: age-standardized incidence rates increased over time in the low (129.2% [38.1 – 306.7%]), lower middle (135.8% [44.5 – 292.7%]), and upper middle (51.3% [6.5 – 121.2%]) income groups, but only changed by 19.2% (-15.0 – 72.1%) in the high income group; age-standardized mortality rates changed by 46.8% (-0.4 – 135.8%) and 34.0% (-6.2 – 107.5%) in the low and lower middle income groups, respectively, but decreased in the high (-27.8% [-33.9 to -21.7%]) and upper middle (-18.5% [-32.6 to -3.4%]) income groups. Between 2024 and 2050 the age-standardized rates were forecast to remain relatively stable for incidence (5.0% [-0.5 – 10.3%]) and mortality (2.2% [-4.5 – 10.2%]), while globally there are forecast to be an estimated 464,000 (305,000 – 614,000) cases and 101,000 (76,400 – 137,000) deaths in 2050. Conclusions: These GBD 2023 estimates provide comprehensive estimates of the substantial health burden of thyroid cancer globally, highlighting a continued need for public health efforts targeting prevention, timely diagnosis, and treatment. These estimates also suggest global disparities in thyroid cancer burden over time.
First-in-human study of ALK201, a FGFR2b-targeting antibody-drug conjugate (ADC) for patients (pts) with advanced solid tumors.
3025 Background: ALK201 is a novel ADC comprising of an anti-FGFR2b humanized monoclonal antibody conjugated to topoisomerase I inhibitor Exatecan via a cleavable and highly hydrophilic linker. ALK201 exhibited potent anti-tumor activities in preclinical studies with a tolerable safety profile. Here we report the preliminary results of ALK201 monotherapy for pts with advanced solid tumors from the first-in-human phase I/II trial (NCT06656390). Methods: This is an ongoing, multicenter, open-label study being conducted in the US, China, and Australia, which consists of two parts, dose-escalation (Part A) and dose-expansion (Part B). The Part A employs the Bayesian optimal interval (BOIN) with backfilling (BF) design to determine the MTD and recommended doses for Part B. In Part A, pts with advanced solid tumors refractory to standard therapies were treated with ALK201 at 1.5-9.6 mg/kg Q3W. Part B was dose expansion at effective doses identified in Part A. The primary endpoint was safety. Secondary endpoints included efficacy and pharmacokinetics (PK). Results: As of December 31, 2025, 38 pts with advanced solid tumors were enrolled in Part A and dosed at 1.5 mg/kg (n=4), 3.0 mg/kg (n=3), 4.8 mg/kg (n=5) ,7.2 mg/kg (n=12), 8.4 mg/kg (n=5) and 9.6 mg/kg (n=9). The median age was 58 years (range 25-74). All pts progressed after receiving a median of 3 prior lines of standard anti-cancer therapy (range 1-8). 28 (73.7%) were Asian and 10 (26.3%) were White. No dose-limiting toxicities (DLTs) have been observed at doses up to 9.6 mg/kg. MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 78.9% pts. The most common TRAEs (incidence ≥10%) were nausea (44.7%), anemia (21.1%), vomiting (21.1%), decreased appetite (13.2%), white blood cell count decreased (13.2%), neutrophil count decreased (10.5%), platelet count decreased (10.5%), AST increased (10.5%), hypoalbuminemia (10.5%) and fatigue (10.5%). Grade ≥3 TRAEs occurred in 23.7% pts and were exclusively reversible hematologic toxicities. Treatment related ocular adverse events limited to grade 1 in 4 pts (10.5%) with minimal clinical impact. Among 25 pts who were evaluable for response, 6 achieved a partial response (PR), 11 achieved stable disease (SD) in best of response. The objective response rate (ORR) and disease control rate (DCR) were 24% (95% CI: 9.4, 45.1) and 68% (95% CI: 46.5, 85.1), respectively. The ORR and DCR in ≥ 7.2mg/kg groups were 35.7% (5/14) and 100% (14/14), respectively. PK analysis showed a dose-dependent ADC and total antibody exposure at doses of 1.5-9.6 mg/kg. ALK201 elimination half-life was approximately 6-11 days. Conclusions: ALK201 demonstrated a favorable safety profile in pts with pretreated advanced solid tumors. Promising anti-cancer activity was observed at doses of 7.2 mg/kg and above, warranting further investigation in those effective dose levels. Clinical trial information: NCT06656390 .
Bone mineral density changes in patients treated with anti-PD-1 immune checkpoint inhibitors.
12107 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment (tx), with almost half of all cancer patients (pts) today eligible for ICI tx. However, these agents frequently cause immune-related adverse events (irAEs). While many irAEs are well-documented, emerging reports suggest that skeletal toxicity may represent an underrecognized complication of ICI tx, particularly with agents that target PD-1. Preclinical models show that global deletion of the PD-1 gene ( Pdcd1 ) or anti-PD-1 tx increases bone resorption, decreases bone formation, and weakens bones. However, skeletal effects remain poorly characterized in humans. We performed a retrospective analysis to assess bone mineral density (BMD) changes via dual-energy X-ray absorptiometry (DXA) results in pts treated with anti-PD-1 ICIs. Methods: We retrospectively analyzed adult pts from a single institution who received at least one dose of an anti-PD-1 agent with or without chemotherapy from 2014 to 2025 and who had pre- and post-tx DXA scans available. We collected demographics, cancer and treatment history, DXA data (including BMD, T-scores, and Z-scores), and scan timing relative to ICI tx. Descriptive statistics and paired t-tests (p<0.05) were used for data analysis. Results: Of 382 pts who received anti-PD-1 tx, 103 had only post-tx DXA scans, and 28 had both pre- and post-tx DXA scans. Of these 28 pts, 93% were female with a median age of 70 at the time of tx (range 58-88). Pts had statistically significant decreases in femur BMD and T-scores pre- vs. post-tx: mean BMD 0.85 vs. 0.81 g/cm 2 (p=0.04) and mean T-score -0.95 vs. -1.66 (p=0.02). Mean Z-scores decreased but were not statistically significant: 0.05 vs. -0.24 (p=0.09). In contrast, there was a trend toward increases in lumbar spine BMD, T-scores, and Z-scores, but none of these changes were statistically significant: mean BMD 1.16 vs. 1.15 g/cm 2 (p=0.93), mean T-score -0.19 vs. -0.06 (p=0.73), and mean Z-score 0.96 vs. 0.99 (p=0.72). Conclusions: This is the largest reported study to date examining BMD changes after anti-PD-1 ICI tx. Although this sample size is small and consists of mostly female pts, these results show significant decreases in femur BMD and femur T-scores after anti-PD-1 ICI tx, resulting in potentially increased fracture risk. T-scores in particular are more accurate in this older pt population than Z-scores. The site-specific changes seen in this dataset align with preclinical studies showing that in female PD-1 knockout mice of all ages, spinal bone mass does not change, but femoral bone mass is reduced. This could reflect differences in cortical vs. trabecular bone or mechanical loading. These findings underscore the importance of skeletal monitoring and indicate that prospective studies are needed to validate the observed bone changes and better characterize fracture risk in patients receiving anti-PD-1 therapy.
Real-world efficacy and safety of tarlatamab in extensive-stage small-cell lung cancer: A single-center retrospective study at university of Missouri.
e20150 Background: Tarlatamab is a standard second-line treatment for extensive-stage small cell lung cancer (ES-SCLC); however, real-world outcome data remain limited. Methods: We conducted a single-center retrospective study at Ellis Fischel Cancer Center, University of Missouri. Adults with ES-SCLC who received prior platinum-based therapy and ≥1 full dose of tarlatamab between May 1, 2024, and December 1, 2025, were included. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), real-world progression-free survival (rwPFS), overall survival (OS), and intracranial PFS (IC-PFS). Safety endpoints included cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and other treatment-related adverse events (TRAEs). Exploratory analyses included subgroup DCRs and post-tarlatamab treatment patterns. Results: Twenty patients were included. Median follow-up was 193 days, and median age was 63 years. At baseline, 70% had brain metastases, 35% had liver metastases, and 30% had received ≥3 prior lines; 30% were platinum-sensitive, and 35% had prior lurbinectedin. The ORR was 30%, and DCR was 40%. Median rwPFS was 90 days (95% CI, 66–NE); median OS was 396 days (95% CI, 113–NE); and median IC-PFS was 71 days (95% CI, 62–NE). Median IC-PFS was 86 days (95% CI, 53–NE) in patients without baseline brain metastases and 71 days (95% CI, 62–NE) in those with baseline brain metastases. CRS occurred in 20% (all grade 1–2), and ICANS in 10% (one grade 1, one grade 3), with median onset times of 12 and 9.5 hours. Steroids, tocilizumab, and ICU admission were required in 25%, 10%, and 10%, respectively. Median cycle 1 hospital stay was 2 days. Other TRAEs included anemia (5%), lymphopenia (10%), hypoalbuminemia (10%), dysgeusia (20%), and one grade ≥3 transaminitis. Subgroup DCRs were 42.9% vs 38.5% (platinum-sensitive vs -resistant), 20.0% vs 46.7% (bulky vs non-bulky), 42.9% vs 33.3% (brain metastases vs none), 28.6% vs 46.2% (liver metastases vs none), and 20.0% vs 46.7% (CRS/ICANS vs none). Of 11 patients who progressed on tarlatamab, only 3 received subsequent systemic therapy (lurbinectedin, n = 2; platinum, n = 1), with treatment durations of 43–104 days. Conclusions: In this single-center real-world cohort, tarlatamab demonstrated safety and efficacy generally consistent with the DeLLphi-304 trial, with lower CRS rates. Few patients received subsequent systemic therapy, highlighting limited post-tarlatamab options. Exploratory subgroup findings suggest potential heterogeneity in treatment response by metastatic pattern and treatment-related toxicity, warranting further investigation. Lastly, most of our patients are suburban and rural patients, emphasizing collaboration with local community oncologists to provide access to tarlatamab in rural settings.
Epigenetic profiling to identify aggressiveness markers in non-Hodgkin lymphoma via a targeted methylation-based multi-cancer early detection (MCED) blood test.
7018 Background: Non-Hodgkin lymphoma (NHL) encompasses a broad spectrum of malignancies, ranging from highly indolent to highly aggressive subtypes, each requiring distinct clinical management strategies. We developed a targeted methylation-based MCED test, and our prior work showed aggressive solid tumors exhibit elevated cell-free DNA (cfDNA) tumor fractions and distinct methylation signatures characterized by high methylated-to-unmethylated (M/U) ratios. This study focused on NHL subtypes to systematically compare epigenetic biomarkers (cfDNA tumor fraction and methylation signatures) for reliable differentiation of indolent and aggressive NHL. Methods: Pretreatment blood samples from NHL patients enrolled in a MCED study were analyzed using the targeted methylation assay. Patients were stratified into aggressive (diffuse large B-cell lymphoma [DLBCL], n=134; mantle cell lymphoma [MCL], n=18; other aggressive NHL, n=2) and indolent subgroups (follicular lymphoma [FL], n=58; marginal zone lymphoma [MZL], n=38; other indolent NHL, n=16). cfDNA tumor fraction was quantified via a zero-inflated negative binomial model, based on the distribution of methylation signal intensities. Methylation profiles were assessed by computing M/U ratios between subgroups. Intergroup comparisons of these biomarkers were conducted using the Mann-Whitney U test, with adjustments for multiple testing. Additional subgroup analyses were stratified by clinical stage to mitigate confounding factors. Results: MCED testing showed higher sensitivity in identifying aggressive NHL subtypes (78.06% vs 67.54% in indolent subtypes), even in stage I-II cases (62.50% vs 46.34% in indolent subtypes). Aggressive subtypes exhibited significantly higher cfDNA tumor fractions than indolent subtypes (Wilcoxon rank-sum test, p=1.27e- 06 ). A total of 31,075 methylation markers (71.66% hypomethylated) showed elevated M/U ratios in aggressive subtypes. These differences in cfDNA tumor fractions and M/U ratios persisted after clinical stage stratification. Conclusions: The MCED assay's superior sensitivity for aggressive NHL suggests preferential detection of aggressive NHL while minimizing indolent NHL overdiagnosis. Aggressive NHL is characterized by elevated cfDNA tumor fractions and distinct methylation profiles with high M/U ratios. These findings demonstrate cfDNA methylation patterns are promising epigenetic biomarkers, enabling aggressiveness differentiation in both solid tumors and NHL. Collectively, this study establishes a potential non-invasive strategy for NHL risk stratification and optimized clinical management.
Urban-rural disparities in the global south: The impact of urbanicity on obesity, comorbidities, and stage at diagnosis in breast cancer.
e13628 Background: Obesity is a major risk factor for breast cancer (BC). With 87.9% of Egyptian women overweight or obese, clarifying the interplay between adiposity, urbanicity, and disease presentation is critical. We evaluated the impact of urbanicity on BMI, comorbidities, and cancer stage at diagnosis in a large Egyptian BC cohort. Methods: We retrospectively analyzed patients at the Baheya Foundation cancer registry. Patients were stratified into High, Moderate, and Low Urban groups based on CAPMAS governorate classifications. Demographics, BMI, comorbidities (DM, HTN, CVD), and clinical stage were compared using ANOVA and Chi-square tests. Results: Among 10,361 patients, 74.0% had obesity (BMI ≥30 kg/m²), exceeding national (49.5%) and international rates, including the UK (17.9%) and North India (33.6%). High Urban patients trended toward the highest mean BMI (34.47 kg/m²; P = 0.092) and had significantly higher comorbidities vs. Moderate and Low Urban groups: DM (30.7% vs. 29.1% vs. 24.8%; P = 0.002), HTN (43.3% vs. 42.5% vs. 36.3%; P < 0.001), and CVD (11.0% vs. 10.8% vs. 8.2%; P = 0.041). Paradoxically, High Urban patients presented significantly earlier (Stage I-II: 53.6%) than Low Urban patients (46.8%; P < 0.001). Conclusions: Egyptian BC patients bear a disproportionate burden of obesity compared to global and national averages. A striking paradox exists: High Urban patients present with a worse metabolic profile yet are diagnosed at earlier stages, likely due to superior access to screening and healthcare facilities. Conversely, Low Urban patients present with more advanced disease despite fewer metabolic comorbidities. These findings highlight the critical role of geographic healthcare disparities in disease prognosis. Future interventions must tailor risk assessment strategies to ethnicity and culture, integrating weight management for urban populations while prioritizing early detection access in less urbanized regions. Baseline patient characteristics by urbanicity. Variable Category High Urban Moderate Urban Low Urban Total p-value Age at diagnosis (years) Mean ± SD 54.11 ± 12.22 53.37 ± 12.23 51.63 ± 12.33 53.35 ± 12.27 <0.001 BMI category (kg/m²) <25 254 (6.5%) 380 (7.0%) 76 (7.2%) 710 (6.9%) 0.86 25–29.9 747 (19.1%) 1,036 (19.2%) 199 (18.8%) 1,982 (19.1%) ≥30 2,900 (74.3%) 3,985 (73.8%) 784 (74.0%) 7,669 (74.0%) Diabetes mellitus 1,039 (30.7%) 1,383 (29.1%) 238 (24.8%) 2,660 (29.2%) 0.002 Hypertension 1,485 (43.3%) 2,040 (42.5%) 350 (36.3%) 3,875 (42.2%) <0.001 Cardiovascular disease 361 (11.0%) 501 (10.8%) 76 (8.2%) 938 (10.6%) 0.04 Clinical stage Early (I-II) 1,891 (53.6%) 2,515 (51.8%) 448 (46.8%) 4,854 (52.0%) <0.001 Late (III-IV) 1,638 (46.4%) 2,337 (48.2%) 510 (53.2%) 4,485 (48.0%)
Postoperative circulating tumor DNA for recurrence risk assessment and adjuvant therapy decision-making in resected colorectal cancer: A systematic review and meta-analysis.
e15633 Background: Circulating tumor DNA (ctDNA) has emerged as a marker of minimal residual disease after curative-intent resection of colorectal cancer (CRC). While multiple studies have shown an association between postoperative ctDNA positivity and disease recurrence, the magnitude and consistency of this risk remain unclear. The role of ctDNA in informing adjuvant therapy decisions is also still evolving. We therefore conducted a systematic review and meta-analysis to evaluate the prognostic significance of postoperative ctDNA in resected, non-metastatic CRC. Methods: We conducted a systematic search of PubMed, Embase, and the Cochrane Library to identify studies evaluating postoperative ctDNA in resected stage I–III Colorectal Cancer. We included prospective cohorts, randomized trials, and observational studies that reported recurrence-related outcomes according to postoperative ctDNA status. The primary outcome was disease-free or recurrence-free survival. Adjusted hazard ratios (HRs) were collected when available. A random-effects meta-analysis was used to pool HRs and compare outcomes between ctDNA-positive and ctDNA-negative patients. Results: We included ten studies of patients with resected stage I–III colorectal cancer (3 from PubMed, 6 from Embase, and 1 from the Cochrane Library). Across all included studies, postoperative ctDNA positivity was associated with a higher risk of recurrence. In the pooled analysis, patients with detectable postoperative ctDNA had a markedly increased risk of recurrence compared with ctDNA-negative patients (HR 9.3, 95% CI 6.1–14.2; p < 0.001). Although variability between studies was observed (I² ≈82%), this was expected given differences in ctDNA assays and study design. The association between postoperative ctDNA positivity and recurrence was consistent across studies. When individual studies with very large effect estimates were excluded, the overall results remained similar. Several studies also reported use of ctDNA-guided approaches. ctDNA-negative patients were able to avoid adjuvant chemotherapy without increased recurrence, while ctDNA-positive patients represented a high-risk group for relapse. Conclusions: Postoperative ctDNA positivity was strongly associated with an increased risk of recurrence in patients with resected colorectal cancer. Across diverse cohorts and assay platforms, detectable ctDNA after surgery represented patients at higher risk for relapse. While approaches incorporating ctDNA to guide adjuvant therapy varied among studies, our findings support the role of postoperative ctDNA as an important prognostic marker. These results highlight the value of ctDNA for postoperative risk assessment and support ongoing prospective trials to clarify how ctDNA should be incorporated into adjuvant treatment decisions.
Clinical outcomes of adjuvant treatment strategies in locally advanced gastroesophageal and gastric adenocarcinoma with poor pathological response to neoadjuvant FLOT: A Turkish Oncology Group (TOG) study.
e16150 Background: Perioperative FLOT is the standard of care for locally advanced gastroesophageal adenocarcinoma. However, the clinical benefit of continuing the same regimen or employing alternative strategies (regimen switch, addition of radiotherapy) in patients with poor pathological response (TRG 2-3) remains unclear. Methods: This multicenter retrospective study included 380 patients with poor pathological response (Ryan TRG 2-3) after neoadjuvant FLOT. Patients with TRG 0-1 and those receiving non-FLOT neoadjuvant therapy were excluded. The impact of R0 resection status, perioperative treatment completion rates, and adjuvant treatment modalities on disease-free survival (DFS) and overall survival (OS) were analyzed. Results: R0 resection was achieved in 83.4% of patients (median age 58.7, 75% male). The perioperative FLOT completion rate was 65.7%. In the adjuvant setting, 82% received FLOT, 10.2% received doublet (FOLFOX/CAPOX) regimens, and 16.2% received adjuvant radiotherapy (RT). For the entire cohort, median OS was 33.0 months (95% CI: 29.6–36.4) and median DFS was 17.0 months (95% CI: 13.8–20.2). OS was longer in the R0 group compared to R1 (34 vs 27 months, p = 0.161). No significant difference was found between adjuvant FLOT and doublet regimens for DFS (18 vs 19 months, p = 0.729) or OS (p = 0.515). The addition of adjuvant RT did not provide additional benefit for DFS (20 vs 18 months, p = 0.436) or OS (p = 0.97) compared to those who did not receive RT. Conclusions: In patients with poor response to neoadjuvant FLOT, continuing FLOT in the adjuvant setting, switching to doublet regimens, or adding radiotherapy did not result in significant survival differences. Novel biomarker-driven studies are needed to determine the optimal adjuvant approach in this high-risk subgroup.
Enhancing hematology-oncology education through a structured AI-based board review series: An ASCO Leadership Development Education Scholars initiative.
9028 Background: As an ASCO Leadership Development Education Scholars Initiative, structured board review is essential for hematology–oncology fellows to consolidate knowledge, support examination readiness, and strengthen clinical decision-making in an increasingly complex therapeutic landscape. Existing approaches are often fragmented and insufficiently tailored to trainee-specific knowledge gaps. To address this need, we developed a pilot, structured board review series within a single academic fellowship program integrating peer-led teaching, faculty mentorship, and anonymous question-based learning aligned with board examination content and real-world oncology practice. Methods: A longitudinal, fellow-led board review curriculum was implemented within a hematology–oncology fellowship program with subspecialty faculty mentorship to ensure clinical accuracy and guideline-based context. Fellows engaged through weekly anonymous board-style multiple-choice questions distributed via Microsoft Teams polls. Questions were curated from ASCO Self-Evaluation Program materials based on high-yield topics identified from ASCO and ASH in-training examinations, with AI-assisted topic prioritization. Objective knowledge acquisition was assessed using identical pre- and post-session questions. Each topic spanned one month with eight pre-session questions and the same eight questions administered post-session. Across five sessions, five fellows answered eight questions per session, yielding 200 learner responses for both pre- and post-intervention assessments. This initiative was conducted as an educational quality improvement project and did not meet criteria for human subjects research. Results: Educational gains were observed across multiple high-yield oncology domains, including molecular biomarker interpretation, guideline-directed therapy selection, toxicity recognition and management, and familiarity with emerging treatment modalities. In the pre-test assessment, 63% of questions were answered correctly (126 of 200 responses). Following the educational intervention, 98% of questions were answered correctly (196 of 200 responses), representing an absolute improvement of 70 correct responses (35%). Conclusions: This structured, fellow-led, faculty-supported board review initiative represents a feasible and effective model for delivering high-yield oncology education within hematology–oncology fellowship training. The curriculum demonstrated measurable knowledge gains, high trainee engagement, and successful integration of AI-informed topic selection with in-training examination data, highlighting the potential for learner-centered curricula to modernize subspecialty medical education and expand to more fellowship programs.