Browse Articles

Failure-to-rescue after acute complications in gastrointestinal cancer hospitalizations in the United States, 2018–2022.

e23118 Background: Inpatient mortality among gastrointestinal (GI) cancer hospitalizations may be influenced not only by the occurrence of acute complications, but also by differences in the ability to rescue patients once complications develop. National data describing failure-to-rescue patterns across hospital settings in GI oncology are limited. Methods: A serial cross-sectional analysis was conducted using the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample. Adult hospitalizations with a principal diagnosis of esophageal, gastric, colorectal, liver or intrahepatic bile duct, or pancreatic cancer were identified. Acute complications were defined using secondary diagnosis codes for bowel obstruction, perforation, gastrointestinal bleeding, and sepsis, combined into an “any complication” indicator. Failure-to-rescue was defined as in-hospital mortality among hospitalizations with at least one acute complication. National estimates accounted for survey weighting, clustering, and stratification. Complication incidence, overall mortality, and failure-to-rescue were summarized by hospital teaching status, bed size, and geographic region. Survey-weighted multivariable logistic regression, restricted to complicated hospitalizations, evaluated factors independently associated with in-hospital mortality. Results: Among GI cancer hospitalizations, 23.1% experienced at least one acute complication. Overall in-hospital mortality was 4.03%, while mortality among hospitalizations with complications was 7.38%. Complication incidence was similar across hospital teaching status, bed size, and region, whereas overall mortality varied across hospital types. Failure-to-rescue among complicated hospitalizations ranged from approximately 6.8% to 9.1% across hospital size and geographic region. In adjusted analyses restricted to complicated hospitalizations, increasing age was associated with higher odds of in-hospital mortality, while female sex was associated with lower mortality. After adjustment, hospital teaching status was not independently associated with failure-to-rescue, whereas hospital bed size and region remained associated with mortality among complicated hospitalizations. Conclusions: Across GI cancer hospitalizations, nearly one-quarter were complicated by acute events, and mortality increased substantially once complications occurred. Although complication incidence was similar across hospital settings, failure-to-rescue varied by hospital size and region. These nationally representative findings provide benchmarking data on rescue outcomes following acute complications in GI oncology.

Role of intraoperative frozen section in detection and surgical decision-making of suspected gallbladder cancer during laparoscopic cholecystectomy.

e16026 Background: Gallbladder cancer (GBC) is an aggressive malignancy with a high incidence in India and is frequently diagnosed at an advanced stage due to nonspecific clinical and radiologic findings. Incidental or intraoperatively suspected GBC during laparoscopic cholecystectomy (LC) represents a critical window for early diagnosis. Intraoperative frozen section (FS) examination may facilitate real-time diagnosis, staging, and appropriate surgical escalation, potentially avoiding re-operations. We evaluated the diagnostic accuracy and clinical utility of FS in suspected GBC during LC. Methods: This retrospective observational study included patients undergoing LC at a tertiary care center between January 2020 and December 2021. Among 1,835 LCs performed, 94 cases with intraoperative suspicion of malignancy underwent FS evaluation. FS samples were obtained from the cystic duct margin, neck, body, and fundus. FS diagnoses were correlated with final paraffin-embedded histopathology, which served as the reference standard. Tumors were staged according to the AJCC TNM system. Diagnostic performance parameters including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. The impact of FS findings on intraoperative surgical decision-making was analyzed. Results: Of the 94 FS-evaluated cases, 26 (27.7%) were confirmed as carcinoma on final histopathology. Xanthogranulomatous cholecystitis was the most common benign mimic. FS correctly identified malignancy in 23 of 26 cases, yielding a sensitivity of 88.5% and specificity of 100%. PPV and NPV were 100% and 95.8%, respectively. Three false-negative cases were attributed to sampling limitations in dysplastic or inflammatory lesions. Pathologic staging revealed pT1b disease in 19.2%, pT2 in 61.5%, and pT3 in 19.2% of patients, with no distant metastases detected. FS findings enabled appropriate intraoperative conversion to radical surgery, including hepatic resection and lymphadenectomy, in eligible patients, thereby reducing the need for second surgeries. Conclusions: Intraoperative frozen section analysis during LC demonstrates high specificity and clinically meaningful sensitivity for detecting unsuspected GBC. FS plays a pivotal role in real-time diagnosis, staging, and surgical decision-making, optimizing oncologic management and minimizing re-interventions. Adequate sampling and experienced pathological interpretation are essential to maximize diagnostic accuracy.

Global patterns and temporal trends of colorectal cancer burden in older adults aged ≥ 70 years.

e15685 Background: Colorectal cancer (CRC) is a major public health concern and represents the second leading cause of cancer-related deaths worldwide and is ranked as the third most common cancer. Despite the advancements in treatment approaches and preventive measures, this cancer remains prevalent in older adults aged ≥70 years. This study evaluates the global trends in Disability-Adjusted Life Years (DALYs), mortality and prevalence from 1990 to 2023 using the GBD (Global Burden of Disease) database. Methods: The Global Burden of Disease (2023) database was used to obtain the data. DALYs, mortality and prevalence rates per 100,000 population among adults aged 70 and older were assessed. We employed joinpoint regression analysis and estimated Annual Percentage Change (APC) for a particular period and Average Annual Percentage Change (AAPC) values for the entire study period. The statistical significance was assessed through p-values less than 0.05 with 95% confidence intervals. Results: DALYs rate per 100,000 increased non-significantly from 202.61 in 1990 to 207.65 in 1993 (APC: 0.69; 95% CI: -0.29 to 1.69; p < 0.16) followed by a significant decline to 197.52 (APC: -0.35; 95% CI: -0.43 to -0.27; p < 0.000001). Then rates increased gradually to 207.73 in 2020 (APC: 0.65; 95% CI: 0.49 to 0.80; p < 0.000001) followed by a sharp rise to 224.97 in 2023 (APC: 2.66; 95% CI: 1.65 to 3.67; p < 0.00001). The AAPC for DALYs rate was 0.346 (95% CI: 0.21 to 0.48; p < 0.000001) The mortality rate increased gradually from 5.29 per 100,000 in 1980 to 6.50 per 100,000 in 2023 with an AAPC of 0.518 (95% CI: 0.40 to 0.63; p < 0.000001). A continuous rise in prevalence rate was observed. From 1990 to 2023, the prevalence escalated from 52.62 per 100,000 in 1990 to 90.91 per 100,000 in 2023. A sharp incline in prevalence occured between 2020 to 2023 (APC:3.56; 95% CI: 2.45 to 4.67; p < 0.000001). Across the entire study period, the AAPC was 1.672 (95% CI: 1.45 to 1.89; p < 0.000001) for prevalence. Conclusions: The prevalence, mortality and DALYs in colorectal cancer in older adults have increased substantially over a study period from 1990 to 2023. This highlights an urgent need for strengthened age-appropriate screening programs, improve preventive strategies and optimize treatment approached to mitigate the disease burden in older adults. Mortality, Disability-Adjusted Life Years, and Prevalence Rates per 100,000 for Adults Aged ≥70 Years Due to Colorectal Cancer. (*shows p < 0.05). Year Mortality Rate (per 100,000) DALYs Rate (per 100,000) Prevalence Rate (per 100,000) 1980 5.293 – – 1990 5.768 202.610 52.623 2000 5.706 201.968 61.401 2010 5.624 197.996 72.162 2023 6.504 224.978 90.914 AAPC (entire period) 0.5183* 0.3463* 1.6726*

Characterization and validation of a methylation signature as a prognostic marker in osteosarcoma.

10016 Background: Despite extensive research efforts, outcomes for patients with osteosarcoma have not substantially improved since the 1980s. Moreover, no prognostic features are used clinically to risk adapt therapy. Here, we performed methylation and RNA sequencing of pre-treatment osteosarcoma tumor samples to identify distinct features of tumor biology and to generate and validate a prognostic signature. Methods: All patients diagnosed with osteosarcoma at the Children’s Hospital of Philadelphia (CHOP) before March 15, 2024 with tissue available for analysis were eligible. Of the 100 eligible patients, three were excluded for lack of clinical data and one for initial diagnostic uncertainty. Methylation and RNA sequencing were performed on DNA and RNA extracted from FFPE or frozen tumor. Unsupervised analyses characterized global methylation structure and differential methylation analyses compared differences between progression groups. Tumor and immune cell fractions were estimated using a reference-based deconvolution algorithm. CpGs were filtered using an unsupervised variability criterion (top 20% MAD) and a ridge-penalized Cox model was used to derive a methylation risk score as a linear predictor. The publicly available TARGET-OS cohort was used for validation with median-based risk stratification defined in the CHOP cohort. Results: Of 96 patients, 44 patients had pre-treatment samples that passed methylation QC and 13 passed RNA sequencing QC. Within the CHOP cohort, 34/44 (77%) had localized disease with a median age of 13 years. Variability in methylation profiles was driven by leukocyte infiltration, supported by strong correlations between global methylation levels and mitotic index estimates. Tumors from patients with progressive disease displayed 12,338 significantly different CpGs (FDR < 0.01) and enriched for hypomethylated CpGs. A methylation-derived risk score was established for overall survival (OS) in the CHOP cohort. In multivariable Cox models, the methylation risk score remained significantly associated with OS (HR 1.54 [1.05–2.26]; p = 0.026) together with metastatic status (HR 5.13 [2.49–10.59]; p < 0.001), yielding improved model discrimination (C-index 0.77 [0.70–0.83]). This was replicated in event-free survival (EFS, HR 2.49 [1.49,4.19], p<0.01). In the TARGET-OS cohort, after adjustment for metastatic status, methylation risk score remained independently associated with EFS (HR 1.6 [1.15, 2.23], p = 0.005). and OS (HR 1.54 [1.05, 2.26], p = 0.003). Conclusions: In this single-institution cohort analysis, a methylation-based risk score predicts survival and adds prognostic value when combined with metastasis status. Integration of CpG methylation with downstream pathway activation via RNA sequencing is ongoing and will be reported. Further validation of this prognostic signature should be considered in future osteosarcoma trials.

Randomized, double-blind, phase 3 TRUST-IV study of adjuvant taletrectinib vs placebo in patients with stage IB–IIIA ROS1+ non-small cell lung cancer (NSCLC).

TPS8130 Background: Taletrectinib is a next-generation, CNS-active, selective ROS1 tyrosine kinase inhibitor (TKI) approved by the US FDA for the treatment of locally advanced or metastatic ROS1+ NSCLC. In stage IB–IIIA NSCLC, which represents about 30% of NSCLC cases, the standard of care is surgical resection with perioperative systemic therapy (neoadjuvant or adjuvant). Results from Phase 3 trials have shown significantly improved outcomes for EGFR and ALK TKIs as adjuvant therapy compared with placebo or chemotherapy in early-stage NSCLC with EGFR mutations or ALK fusions, respectively. However, there remains an unmet need for patients with stage IB–IIIA ROS1+ NSCLC. Given the efficacy and tolerability of taletrectinib in advanced ROS1+ NSCLC, there is a rationale for investigating taletrectinib in patients with earlier-stage NSCLC who have undergone complete tumor resection. Methods: TRUST-IV (NCT07154706) is a randomized, double-blind, multicenter, Phase 3 study evaluating the efficacy and safety of taletrectinib compared with placebo in patients with stage IB, II, or IIIA ROS1+ NSCLC following curative surgery (negative surgical margins). ROS1 fusions may be detected using validated local tissue or liquid assays but must be confirmed by central tissue testing. Patients may have received prior adjuvant platinum-based chemotherapy (≤4 cycles) if clinically indicated, which must be completed ≥7 days prior to randomization. Surgical resection must have occurred 4–16 weeks prior to randomization if no adjuvant chemotherapy was given or 4–30 weeks if adjuvant chemotherapy was given. The estimated enrollment is 180 patients, randomized 2:1 to receive either taletrectinib 400 mg once daily or a matched placebo, stratified by prior adjuvant chemotherapy (yes vs no) and pathological stage (IB vs II vs IIIA). Patients will receive blinded study drug in continuous 28-day cycles until disease recurrence or consent withdrawal, or up to a maximum of 3 years. Contrast computed tomography or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis will be performed at screening, Cycle 4 Day 1 (C4D1), and C7D1, while brain MRI will be performed at screening and C7D1; thereafter, all imaging will be performed every 24 weeks until 5 years and then annually until disease recurrence or end of study. The primary endpoint is disease-free survival (DFS) by investigator assessment. Select secondary endpoints include: DFS rates at 2, 3, 4, and 5 years; DFS by blinded independent central review; overall survival; CNS-DFS; and safety. Exploratory endpoints include patient-reported outcomes for health-related quality-of-life measures and progression-free survival 2. The trial is currently recruiting. Clinical trial information: NCT07154706 .

Adjuvant capecitabine and trastuzumab for stage IA HER2-positive breast cancer (IRIS-A): A phase II clinical trial.

508 Background: Weekly paclitaxel and trastuzumab represents a standard option for most stage I human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC)s based on results of the single arm phase II APT trial. However, the protocol-induced toxicity was not absent, prompting interest in better tolerated approaches that retain high clinical efficacy. The series of “IRIS” study including cohort A(2020, capecitabine and trastuzumab), B(2020, endocrine therapy and trastuzumab), C (2021, short-period capecitabine and trastuzumab) and D (2021, vinorelbine and trastuzumab) were designed as single arm trials regarding de-escaltion of adjuvant therapy without intravenous chemotherapy in early-stage HER2+ BCs. Herein we reported the results of IRIS-A, a single-group, phase II study to determine whether treatment with capecitabine and trastuzumab was well tolerated and yielded clinically acceptable outcome among stage IA HER2-positive breast cancer. Methods: Patients with stage IA (T1N0: hormonal receptor (HR) < 10%, T≤2cm or HR≥10%, 1cm < T≤2cm) confirmed HER2+ BC were received oral capecitabine (1000 mg/m 2 twice daily for two weeks), and trastuzumab( 8 mg/kg load→6 mg/kg) every 3 weeks for 6 cycles, followed by 11 cycles of trastuzumab monotherapy (6 mg/kg once every 3 weeks). The primary end point was survival free from invasive disease (iDFS). Results: A total of 187 patients were enrolled in this study between May 20, 2020 and May 27, 2021 at Fudan University Shanghai Cancer Center in China. Among all these patients, 80.2% had tumors that measured 0.5 cm or less in the greatest dimension; a majority of tumors (87.2%) were hormone-receptor-negative. The median follow-up period was 62 months( ranges 56-68). The 5-year rate of survival free from invasive disease was 97.9% (95% confidence interval [CI], 94.4 to 99.2). Among the 4 relapses seen, 2 were due to contralateral primary invasive breast cancer (HER2-negative). Excluding these 2 patients and nonbreast cancers, 2 disease-specific events (1 with ipsilateral axilla and ipsilateral breast) were noted. There was no death in this trial. A total of 5 patients (2.7%) reported at least one episode of grade 3 adverse effect (AE)s, which did not influence the completion of treatment. The most common AE was hand-foot syndrome (46.5%), with 1.1% of patients experiencing a grade 3 event. Conclusions: Among patients with stage IA HER2+ BCs, treatment with adjuvant capecitabine plus trastuzumab was associated with an excellent 5-year iDFS of 97.9%. No adverse events that influence treatment continuity were observed. The regimen used in this trial would be an alternative in patients with small size HER2+ tumors with fewer toxic effects than the established regimens. A phase III study using the same protocol is being conducted currently. Clinical trial information: NCT04383275 .

Oncoseek 2.0: An updated blood-based assay for multi-cancer early detection.

10551 Background: Early identification of cancer remains essential for improving survival and reducing downstream treatment costs, yet effective and scalable multi-cancer screening strategies are still limited. OncoSeek is a previously validated, AI-based multi-cancer early detection (MCED) assay integrating protein tumor markers (PTMs) with clinical data, demonstrating 58.4% sensitivity, 92.0% specificity, and 70.6% tissue-of-origin accuracy in > 15,000 participants. To improve detection of specific cancer types and expand cancer-type coverage, we developed OncoSeek 2.0 by incorporating three additional PTMs and evaluated its performance in validation cohort. Methods: OncoSeek 2.0 retained the original machine-learning framework of OncoSeek 1.0, with expanded PTM inputs (ProGRP, SCCA, and tPSA). Performance was evaluated in a retrospective validation cohort comprising 1,267 cancer and 355 non-cancer individuals. Overall performance, including cancer-type-specific sensitivity, was assessed and compared with OncoSeek 1.0. Results: OncoSeek 2.0 incorporated three additional PTMs (ProGRP, SCCA, and tPSA) to enhance cancer-type–specific detection. ProGRP levels was significantly elevated in small cell lung cancer compared with other cancers and healthy controls; SCCA concentrations were higher in squamous cell carcinomas (esophageal, cervical, and lung) than in non-squamous cancers and controls; and tPSA was selectively increased in prostate cancer (all P < 0.0001). Compared with OncoSeek 1.0, OncoSeek 2.0 achieved a higher AUC (0.917 vs 0.860) and improved sensitivity from 65.3% to 77.6% at 90.1% specificity across 15 pre-specified cancer types collectively accounting for 76.5% of global cancer mortality. Sensitivity gains were notable in lung (75.1% → 84.3%), prostate (58.8% → 88.2%), cervical (55.6% → 65.6%), and esophageal (39.6% → 62.4%) cancers. When stratified by tumor stage, OncoSeek 2.0 achieved sensitivities of 54.2% for stage I, 71.7% for stage II, 79.8% for stage III, and 88.4% for stage IV, consistently outperforming OncoSeek 1.0, which achieved sensitivities of 30.2%, 53.8%, 62.3%, and 85.7% for stages I through IV, respectively. Conclusions: By integrating three additional cancer-type–specific PTMs, OncoSeek 2.0 substantially improves sensitivity while maintaining high specificity and low reagent cost (~$30 per test). The upgraded assay enhances detection across multiple tumor types and disease stages, with particularly pronounced gains in lung, prostate, cervical, and esophageal cancers. These results support OncoSeek 2.0 as a scalable and clinically actionable MCED approach for population-level early detection, particularly for cancers lacking USPSTF-recommended screening and in low- and middle-income countries.

Trends in incidence, survival, and cause of death in Kaposi sarcoma in the antiretroviral therapy era.

1563 Background: Kaposi sarcoma (KS) is a malignancy driven by human herpesvirus-8 infection and is most commonly associated with HIV. Although often considered indolent, KS can cause significant morbidity and mortality, particularly if HIV is uncontrolled. This study aimed to characterize current incidence and survival trends in KS using the Surveillance, Epidemiology, and End Results (SEER) Database. Methods: Cases of KS were identified using ICD-O-3 codes 9140-9143 in the SEER Research Plus Data (17 Registries, 2000-2022). SEER registry incidence rates were calculated over time. Overall survival (OS) across diagnostic eras was estimated using Kaplan-Meier methods. Multivariable Cox models were used to assess associations between race/ethnicity, neighborhood income, rural-urban status, and mortality, adjusting for age, sex, and year of diagnosis. Cause-of-death analyses were performed using SEER cause-specific recodes. Results: 9,931 patients with KS were identified, 91% male and 9% female. Racial and ethnic distribution was 45% non-Hispanic White (NHW), 24% Hispanic, 24% Black, 3.7% Asian/Pacific Islander (A/PI), and 0.7% American Indian/Alaska Native (AI/AN). Registry incidence of KS declined from 0.33 per 100,000 in 2000-2004 to 0.22 in 2015-2019 and 0.20 in 2020-2022. One-year OS in 2000-2004 was 77.3% (95% CI 75.7-78.9), in 2015-2019 was 82.2% (95% CI 80.4-83.9), and in 2020-2022 was 80.9% (95% CI 78.3-83.5). In multivariable analyses, Black patients had higher mortality compared with NHW patients (HR 1.55, 95% CI 1.43-1.67), while mortality did not differ significantly among Hispanic, A/PI patients, or AI/AN patients. Residence in the highest neighborhood income quartile was associated with improved overall survival compared with the lowest quartile (HR 0.81, 95% CI 0.73-0.89). Across 2000-2022, HIV/infectious causes accounted for 55.6% of deaths (95% CI, 53.9-57.2), followed by cardiovascular disease (15.1%) and cancer-related causes (13.3%). In cause-specific analysis, later year of diagnosis was strongly associated with lower HIV/infectious mortality (HR 0.96 per year, 95% CI 0.96-0.97), whereas mortality from cancer did not improve over time. Conclusions: In the modern antiretroviral therapy era, KS incidence and HIV-related mortality have declined. Despite these advances, inequities persist, with higher mortality observed among Black patients and persons residing in poorer neighborhoods. These findings highlight the need for focused efforts to address disparities in KS outcomes. Adjusted hazard ratios for overall survival in Kaposi sarcoma. Variable Adjusted HR 95% CI P value Race/Ethnicity Non-Hispanic White Reference - - Black 1.55 1.43-1.67 <0.001 Hispanic 1.02 0.95-1.11 0.54 Asian/Pacific Islander 1.02 0.86-1.20 0.82 American Indian/Alaska Native 1.26 0.89-1.80 0.20 Neighborhood Income Highest vs Lowest Quartile 0.81 0.73-0.89 <0.001

Whole-genome sequencing–based ultra-sensitive ctDNA molecular residual disease assessment in resectable gastric cancer: Results from MONSTAR-SCREEN-3.

4081 Background: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for post-surgical molecular residual disease (MRD) detection; however, its clinical utility in gastric cancer remains poorly defined. The MONSTAR-SCREEN-3 evaluates the clinical performance of a whole-genome sequencing (WGS)–based MRD assay in a pan-cancer cohort, including patients with gastric cancer. Methods: MONSTAR-SCREEN-3 is a prospective multicenter study targeting 1,100 patients with solid tumors curative-intent treatment, including gastric cancer. Personalized panels were constructed using Precise MRD (Myriad Genetics), incorporating up to 1,000 tumor-specific alterations identified through whole-genome sequencing (WGS) of matched tumor tissue. Serial plasma samples were collected at baseline, post-neoadjuvant treatment (NAT) when applicable, 1-month post-surgery, every 3 months in year 1, and every 6 months thereafter up to 2 years. Assay performance was evaluated for ctDNA detection and recurrence monitoring. Results: As of November 2025, 88 patients with resectable gastric cancer were enrolled. Median age was 69 years (range: 33-87), with female predominance (52.2%). Treatment strategies included upfront surgery (56%, n = 49) and NAT (44%, n = 39). MRD results were available for 220 samples from 57 patients. Clinical staging included Stage I (6%), Stage II (39%), Stage III (51%), and Stage IV (5%). Personalized panel creation succeeded in 100% of patients (57/57), yielding panels containing 588-1,000 alterations. Baseline ctDNA detection was achieved in 96.4% (54/56), with 31.5% at ultra-sensitive levels (tumor fraction < 100 parts per million [ppm]). Post-operative MRD positivity was 7.8% (4/51) at 1 month and 19.5% (8/41) at 3 months, with 25.0% and 50.0% detected at ultra-sensitive levels, respectively. Among 24 patients receiving NAT with pathological assessment, post-NAT MRD status demonstrated 70.0% sensitivity and 100% specificity for pathological complete response (pCR) (MRD positivity, 70% in non-pCR vs. 0% in pCR; P < 0.01); 57.1% of MRD-positive cases were detected at ultra-sensitive levels. Two MRD-positive patients developed radiological recurrence, with MRD detection preceding imaging by 2.0 and 4.3 months. Conclusions: This WGS-based personalized ctDNA assay demonstrated high technical feasibility and baseline detection sensitivity in gastric cancer, with notable ultra-sensitive detection capability. Post-NAT MRD status demonstrated potential as a predictor of pathological complete response. Extended follow-up and comprehensive longitudinal ctDNA dynamics will be presented.

Oncofertility counseling practices in AYA patients diagnosed with stage I-III breast cancer.

e12685 Background: Approximately 12,000 women under 40 years are diagnosed with breast cancer annually in the US, representing 7% of all cases. Cancer-directed therapy may adversely impact fertility through chemotherapy-associated premature ovarian insufficiency and delays in childbearing related to prolonged endocrine therapy. ASCO guidelines recommend oncofertility assessment at diagnosis, including counseling on treatment-related reproductive risks and referral for fertility preservation (FP). Available FP methods (oocyte/embryo cryopreservation, ovarian tissue cryopreservation, and ovarian suppression) should be discussed prior to initiation of cancer-directed therapy. Despite established safety and efficacy of FP, barriers to care persist, including limited access to oncofertility counseling and FP services, as well as delays in chemotherapy initiation. We conducted a retrospective review to assess real-world oncofertility counseling practices over a 10-year period among adolescent and young adult (AYA) patients aged 15-39 with breast cancer. Methods: We conducted a retrospective cohort study of patients diagnosed with invasive breast cancer before age 40 from 2013-2023 at a tertiary medical center (n = 498). Exclusion criteria included male sex, stage IV disease, no receipt of chemotherapy, and absence of documented oncofertility counseling prior to systemic therapy. Oncofertility counseling practices and clinicodemographic variables (age, race, ethnicity, stage, and parity) were abstracted from the EMR. We performed univariate analyses to evaluate the associations between oncofertility counseling and clinicodemographic characteristics. Results: Of 281 women under 40 with stage I-III breast cancer who received chemotherapy, 132 (47%) had oncofertility counseling prior to therapy. Counseling rates were highest in the 20-25 age group (85%) and lowest in the 36-39 age group (30%). Counseling rates differed by parity (68% nulliparous, 48% one child, 30% ≥2 children; p < 0.001) but not by race/ethnicity (p=0.69). Among counseled patients, 67 (51%) expressed interest in FP, of whom 65% received a reproductive endocrinology (REI) referral and 70% received FP treatment. The most used FP strategy was GnRH agonist (61%), followed by oocyte/embryo cryopreservation (9%), and combined approaches (16%). Conclusions: Oncofertility counseling was associated with increased utilization of FP interventions. In our study, counseling rates varied significantly by parity, with nulliparous women more likely to receive counseling, while no significant differences were observed by race and ethnicity. Among counseled patients interested in FP, the majority received a referral to REI and proceeded with FP treatment. These findings underscore the importance of systematic integration of oncofertility counseling at diagnosis, prior to initiation of cancer therapy.

Transforming patient care in oncology: Nationwide results of comprehensive genomic profiling–guided therapy in everyday clinical practice.

e23420 Background: In recent years, precision medicine has become one of the most thought-provoking concepts in healthcare, especially in oncology, fundamentally transforming the way patient care is delivered. Recent advancements in sequencing technologies have substantially reduced the costs associated with comprehensive genomic profiling (CGP), facilitating its integration in routine practice. Also, innovative treatment strategies have already produced remarkable improvements in outcomes for several cancer types. However, with ambiguous results from clinical trials, the importance of real-world data is increasingly recognized. As a further development of our previously published CGP analyses, we present the CGP-guided treatment results at the national level for the first time. Methods: The study was retrospective, conducted at the country level among all patients who were administered with CGP-guided therapy from January 1, 2020, to December 31, 2025. The analysis was performed in an accredited laboratory (Foundation Medicine Inc., Cambridge, MA, USA or Personalized Medicine Department, UHC Zagreb, Croatia). Patients were administered with CGP-guided therapy following recommendations from Multidisciplinary Tumor Board (MTB) either in later-line settings (95%), or when first-line reimbursement was not available (5%). Progression-free survival (PFS) was measured from the initiation of either CGP-guided to the occurrence of disease progression, death from any cause, or the most recent follow-up (with data censored accordingly), whichever event transpired first. Results: There was a total of 4150 of tested patients, out of whom 339 (8%) patients were treated according to their CGP results. Median age was 63 years (IQR 53-69), and 58% of patients were women, while 42% were men. Most commonly treated were lung (16%), uterine (12%), ovarian (11%), breast (11%), and colon (9%) cancer. Median number of previous lines was 2 (IQR 1-3), with 29% of patients who received at least 3 lines of therapy. The most common therapy administered was olaparib in 63 (18.5%) patients, following were pembrolizumab and trastuzumab-deruxtecan in 50 (14.7%) and 31 (9.1%) patients, respectively. Median progression-free survival (PFS) was 4.7 months (IQR 2.1-10.6). The data were missing for 4 (1.2%) patients, and they were excluded from analysis. Notably, 43% achieved PFS > 6 months and 21% exceeded 12 months, with 10.5% surpassing 18 months. As of January 25, 2026, 41.9% remained on therapy without progression. Conclusions: Our results have shown that despite a heavily pretreated, refractory population of patients, a mPFS of 4.7 months and 21% of patients exceeding 12 months PFS defines potential and value of precision medicine approach in oncology. Given the time elapsed since data collection and the inclusion of recently treated patients, an updated data analysis is warranted.

Longitudinal inherited cancer care and its impact in a rural setting.

e22665 Background: Hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS) are associated with elevated cancer risk. Many effective cancer prevention and surveillance strategies are recommended but uptake is suboptimal. The impact of rurality on adherence to cancer prevention and surveillance strategies and on the psychological impact and perception of care coordination in this patient population is not well understood. Methods: Patients seen > 1 year ago by our institution’s Cancer Genetics Program with a known diagnosis of LS or HBOC were recruited for participation. Enrolled patients completed a baseline Care Coordination Instrument (CCI) and Multidimensional Impact of Cancer Risk Assessment (MICRA) survey. Patients completed a clinic visit with a cancer genetics provider, and recommended changes in cancer prevention or surveillance strategies were collected. We evaluated the association between residential rurality and participation rate. Rurality was based on Rural-Urban Commuting Area (RUCA) codes, mapped to residential ZIP code. RUCA > 7 was classified as rural to capture the most rural participants. We fit multivariable log-binomial and linear regression models to estimate associations between rurality and participation, CCI, and MICRA, adjusting for age and genetic syndrome. Results: 223 people with LS and HBOC living in VT or NY were screened and eligible. Seventy-seven participants (35%) enrolled. Of the 146 patients who did not enroll, 32 (22%) are still pending enrollment, 21 (14%) declined, and 93 (64%) have not responded to outreach. Rurality was not a predictor of enrollment (RR adj = 0.93, 95% CI:0.63, 1.40). HBOC patients were more likely to enroll compared with LS patients (RR adj = 1.9, 95% CI:1.2, 2.8). Males were somewhat less likely to enroll (RR adj = 0.79, 95% CI: 0.40,1.6). Of enrolled participants, 69 (90%) were natal females and median age was 47 years (range 28-78). The majority of enrolled patients (n = 47, 65%) had not seen a genetics provider in >5 years. Mean MICRA scores were 29.1, higher than previously published scores after genetic testing. Mean CCI scores were 49.6, indicating lower care coordination. MICRA and CCI scores were similar among rural and non-rural patients. HBOC patients had higher CCI scores compared with LS patients. A change in clinical care was recommended for 59 participants (81%), including increased interval or new screening modality for 38 (53%), decrease in screening frequency for 16 (22%), referral to specialist for 26 (36%), and initiation of chemoprevention for 18 (25%). Conclusions: A substantial proportion of eligible patients enrolled in this opportunity for cancer genetics follow-up. Rurality was not associated with choice to enroll. The psychological impact after genetic testing and perception of care coordination were similar between rural and non-rural patients. Analyses demonstrate the high impact of cancer genetics clinic visits for patients with LS and HBOC. Clinical trial information: STUDY00002507/UVMCC2204.

Structural coloration for photovoltaics via sub-monolayer disordered Mie resonators

Building-integrated photovoltaics (BIPV) are currently hindered by the esthetic trade-off between power conversion efficiency and visual appeal. Conventional colorization methods generally fall into two categories: organic absorption-based dyes, which suffer from high parasitic losses and limited durability, and interference-driven multilayer thin films stacks, which exhibit undesirable iridescence. In this work, we demonstrate highly stable, largely angle-independent color PV modules utilizing a disordered sub-monolayer of dielectric silicon nanoparticles (Si NPs). By leveraging localized Mie resonances within high-index Si nanospheres (100–200 nm in diameter), the angle-dependence of the reflected color is strongly reduced. These Si NPs are encapsulated in a protective polymer shell to prevent clustering, thereby maintaining sharp scattering peaks and color saturation. The nanostructures were deposited via slot-die coating, providing a scalable fabrication route for large-area modules (∼50 cm2 PV devices demonstrated here). Numerical simulations support the experimentally observed spectrally selective reflectance driven by such Si NPs photonic glasses. We achieve a relatively broad CIE 1976 color gamut, including saturated blue, green, and yellowish hues, by varying the size and surface density of Si NPs while maintaining less than 10%–20% relative photocurrent PV loss. This offers a versatile design palette for high-efficiency, esthetically pleasing urban BIPV energy harvesting.

Green synthesis of copper oxide nanoparticles from Santalum album and their adsorption performance, reliability modeling, and agro-stimulatory effects on wheat

Accelerated diagnostic pathway for undifferentiated malignancy via interventional radiology triage: A comparative effectiveness study.

1568 Background: Efficiently triaging patients presenting with imaging findings suggestive of malignancy but lacking a definitive tissue diagnosis poses a considerable challenge for large cancer centers. Without a tissue diagnosis in the setting of metastatic disease it is unclear which specialized medical oncologist would be the optimal physician to see the patient. Traditional referral patterns may lead to significant diagnostic delays until the patient reaches the appropriate oncologist. We evaluated the efficacy of a dedicated "Rapid Biopsy" (RB) pathway, which directs such patients immediately to the Interventional Radiology (IR) Outpatient Clinic for streamlined, image guided diagnosis and compared this new pathway to the traditional, standard institutional referral approach. Methods: This retrospective cohort study included 1157 patients at Memorial Sloan Kettering Cancer Center (MSKCC) who underwent a first diagnostic biopsy between 2020 and 2023. The cohort comprised 532 patients from the prospectively enrolled RB program and 625 patients in a rigorously matched comparison cohort (CC), derived from standard referrals who presented with an "unknown primary" malignancy, excluding any patient with a history of prior tissue sampling or recurrence. The primary endpoints were the mean time from initial consultation to biopsy and the mean time from initial consultation to treatment initiation. Independent t-tests were used for cohort comparison. Patients exhibiting outlier time-to-treatment intervals exceeding 90 days were excluded from the treatment analysis. Results: The RB and CC cohorts were well-matched demographically (mean age RB: 65.75 years; CC:66.05 years). Malignancy was confirmed in 90.4% and 92.3% of the respective cohorts. The RB pathway demonstrated a 71% reduction in time from initial consult to biopsy than the CC (4.59 vs 15.66 days, p<0.001), representing an 11.07 reduction. Furthermore, this operational efficiency translated into a 63% reduction in time from initial consult to treatment compared to the CC (14.57 vs 39.88 days, p<0.001), achieving an 11.88 day reduction in time to start. Conclusions: The dedicated Interventional Radiology first Rapid Biopsy pathway provided a clinically significant meaningful acceleration in the cancer diagnostic and treatment process, saving 11 days from consult to biopsy and nearly 12 days to definitive treatment initiation. This model effectively streamlines care by eliminating multi-specialty diagnostic detours prevalent in traditional triage, establishing a crucial operational standard for comprehensive cancer centers managing new suspected malignancies.

An AI-integrated patient-derived organoid platform to enable high-throughput drug response prediction in glioma.

e14086 Background: Glioma exhibits pronounced heterogeneity in both the tumor microenvironment and molecular subtypes, leading to substantial inter-individual variability in drug response and posing major challenges for therapeutic prediction and clinical decision-making. However, current in vitro glioma models remain insufficient for rapid, cost-effective, and biologically faithful high-throughput drug screening. To address these limitations, we integrated patient-derived glioma organoids with artificial intelligence–based modeling to establish an improved framework for treatment response evaluation. Methods: An AI agent was used to systematically curate transcriptomic and pharmacological data from publicly available literature and databases. We developed AI4Med, an integrative translational framework that combines patient-derived glioma organoids with AI-based predictive modeling. Multiple complementary algorithms—including gradient boosting methods (LightGBM, XGBoost, CatBoost), tree-based ensembles (Random Forest, Extra Trees), K-Nearest Neighbors, and Neural Networks—were integrated to capture diverse transcriptomic patterns. For each drug, an independent regression model was trained to predict IC50 values. Feature selection was performed by ranking genes according to predictive importance, retaining the top 100 genes per drug to reduce dimensionality and improve generalization. In parallel, a high-throughput organoid-based drug screening system was established and validated against matched native tumors for molecular fidelity and drug response consistency. Results: Model training was conducted using curated transcriptomic and pharmacological data comprising 1,406 cancer cell lines, 481 chemical compounds, and 860 cancer cell line models. Transcriptomic features were represented at the pathway level, with drug-specific pathway weighting applied during model optimization. Using an ensemble-based strategy, AI4Med demonstrated robust predictive performance, which was further refined and independently validated using patient-derived glioma organoid drug screening assays. In organoid-based validation, the model achieved a top-5 drug sensitivity prediction accuracy of 97% and a top-10 accuracy of 85%, enabling early identification of patient-specific therapeutic vulnerabilities. Conclusions: We established an AI-integrated, high-throughput drug screening platform for glioma, supported by real-world experimental validation using patient-derived organoids. This biologically grounded and scalable framework enables precision drug selection in glioma and may be extended to other heterogeneous malignancies, highlighting its broad translational potential.

Safety and efficacy of sacubitril/valsartan for prevention of anthracycline-related cardiotoxicity: A meta-analysis of randomized controlled trials.

e24010 Background: Anthracycline chemotherapy is a cornerstone of therapy for breast cancer and multiple other malignancies, but its clinical utility is limited by cardiac dysfunction related to cancer therapy (CTRCD). CTRCD is characterized by a decrease in left ventricular ejection fraction (LVEF) with observed rates of asymptomatic cardiac dysfunction in up to 20–30% and overt heart failure (HF) in 5–10% of patients. No standard drug regimen has been established to prevent this. Sacubitril/valsartan (S/V) is widely used to improve outcomes in HFrEF and has been evaluated in recent randomized controlled trials (RCTs) for its potential cardioprotective role in patients receiving anthracycline chemotherapy. In this study, we analyzed RCT data to evaluate the safety and efficacy of S/V for preventing CTRCD in anthracycline-treated patients. Given the lack of established pharmacologic prevention strategies, synthesizing emerging RCT data on S/V may help clarify its potential role in mitigating CTRCD risk. Methods: PubMed, Scopus, ClinicalTrials.gov, and Cochrane Library were searched from inception through January 2026. Eligible studies were RCTs comparing S/V with control (standard care) in patients receiving anthracyclines. CTRCD was defined as ≥15% decline in global longitudinal strain (GLS) or ≥10% absolute LVEF reduction to <50%. Safety analysis focused on hypotension, the most commonly reported adverse event. A random-effects model was used with Revman v5.4, and results with p-values under 0.05 were interpreted as significant. Risk of bias was assessed using the revised Cochrane “Risk of bias” tool for randomized trials (RoB 2.0). Results: Our initial search yielded 12 studies. Three RCTs (SARAH, PRADA II and Hsu et al.), all published in 2025 and enrolling 350 patients in total, met inclusion criteria. Across these trials, S/V significantly reduced CTRCD incidence (RR 0.24, 95% CI 0.10–0.61; I² = 0%; P = 0.003). Hypotension occurred more frequently in the S/V group (RR 4.42, 95% CI 1.59–12.28; I²=0%; P = 0.004). All RCTs were assessed to have low risk of bias. Conclusions: This meta-analysis provides the first synthesis of RCTs evaluating S/V for CTRCD prevention in anthracycline-treated patients, all published in 2025, offering an early evidence base for future trials. S/V significantly reduced the incidence of CTRCD with consistent effects and minimal heterogeneity, supporting its role as a potential strategy for CTRCD prevention. While hypotension was the most reported adverse effect, events were reported as mild and manageable with dose adjustment, underscoring the importance of careful monitoring. Our study is limited by its sample size. Larger multicenter trials powered for long-term clinical outcomes, such as the MAINSTREAM trial projected to complete in 2027, are warranted to confirm or refute these findings.

Calibration of commercial AI chatbots for cancer symptom recognition: A pilot methodology study.

e13698 Background: AI chatbots are increasingly used for health queries, yet their calibration for cancer recognition remains uncharacterized. How should AI respond to users with varying health literacy presenting equivalent clinical scenarios? Methods: We developed 114 calibrated queries across 10 cancer types, three pretest probability scenarios (high, low, diagnostic trap), and three user personas (naive patient, sophisticated patient, expert clinician) presenting equivalent clinical scenarios with varying linguistic framing. Each query was submitted to Claude, ChatGPT, and Gemini (n = 342 evaluable responses). Responses were scored using a keyword-matching algorithm. Results: Algorithm-derived Expected Calibration Alignment was 76.0% overall. High pretest probability scenarios showed 89.6% alignment; low pretest showed 38.9%, suggesting frequent over-escalation. Response thoroughness varied by persona: expert queries elicited responses ~2x longer than naive queries across all platforms. Expert responses included pre-test probabilities and workup protocols; naive responses provided general advice to "see a doctor." Conclusions: Current AI chatbots calibrate response thoroughness to query sophistication rather than clinical need. This raises alignment questions with equity implications: should AI proactively provide detailed guidance to users who don't know to ask for it? Data available via OSF.

Early mortality in patients with advanced non–small cell lung cancer (aNSCLC) and PD-L1 ≥ 50% receiving first-line immune checkpoint inhibitor (ICI): Analysis of the NOTCH collaborative REAL-SAIF study.

e20684 Background: Single-agent ICIs are approved for the first-line treatment of aNSCLC and PDL1 ≥50%. Early cross-over of survival curves raise concerns about early mortality in this group. Current controversies exist about upfront intensification with ICI-chemotherapy and the increasing use of ICIs in patients near the end-of-life. To our knowledge, this is one of the largest study to explore early mortality in patients with aNSCLC receiving single-agent ICI. Methods: 1571 patients treated between 2017-2023 from 18 UK centres were included into this retrospective real-world study. Multiple imputations were used to handle data missing at random and pooled estimates were combined. Multivariate logistic regression was used for 30- and 60-day mortality. Variables were selected through a combination of domain knowledge and LASSO regression. Results: 5.6% and 12.4% of patients experienced 30- and 60-day mortality respectively. Baseline demographics within total cohort were median age 70-years, 52% male, 76% non-squamous histology, 14% brain metastases, 11% liver metastases, 76% de-novo stage 4 disease, and 93% pembrolizumab as ICI of choice. Performance status (PS) of ≥2 (OR 2.36; p <0.001), neutrophil-lymphocyte ratio (NLR) (OR 1.21; p =0.008), neutrophil-eosinophil ratio (NER) (OR 1.33; p <0.001), and albumin (OR 0.88; p <0.001) were associated with 30-day mortality [Table 1]. PS ≥2 (OR 1.77; p <0.001), NLR (OR 1.39; p <0.001), NER (OR 1.29; p <0.001), albumin (OR 0.89; p <0.001), brain metastasis (OR 1.99; p =0.002), and liver metastasis (OR 1.88; p =0.007) were associated with 60-day mortality. Age, sex, BMI, smoking status, histology, and deprivation indices were not associated with 30- or 60-day mortality. Most common cause of 30-day death was NSCLC (79.6%) followed by non-cancer causes (11.4%). Conclusions: Poor PS and elevated inflammatory indices (NLR, NER, albumin) were associated with 30-day mortality, reflecting systemic effects of disease and/or patient frailty. The latter emergence of brain and liver metastases as 60-day prognostic markers may indicate the need for ICI-chemotherapy combination in fit patients. Multivariate logistic regression for 30-day and 60-day mortality. 30-day mortality[OR (95%CI); p -value] 60-day mortality[OR (95%CI); p -value] Age 0.98 (0.96-1.00) 0.086 1 (0.98-1.02) 0.907 Performance status ≥2 2.36 (1.63-3.42) <0.001 1.77 (1.31-2.39) <0.001 Haemoglobin 1.02 (1.00-1.03) 0.023 1.01 (1.00-1.02) 0.064 Albumin 0.88 (0.84-0.91) <0.001 0.89 (0.86-0.91) <0.001 NLR 1.21 (1.05-1.39) 0.008 1.39 (1.18-1.65) <0.001 NER 1.33 (1.14-1.54) <0.001 1.29 (1.12-1.48) <0.001 Brain metastasis – – 1.99 (1.29-3.06) 0.002 Liver metastasis – – 1.88 (1.19-2.98) 0.007 Index of Multiple Deprivation – – 1.06 (1.00-1.12) 0.062

Comparative efficacy of neoadjuvant immunochemotherapy versus chemoradiotherapy in resectable esophageal squamous cell carcinoma: A component network meta-analysis.

e16068 Background: Neoadjuvant chemoradiotherapy (CRT) is the current standard for resectable esophageal squamous cell carcinoma (ESCC), yet the role of immune checkpoint inhibitors (ICI) remains unclear. We performed a component network meta-analysis (CNMA) comparing CRT, ICI plus chemotherapy, and chemotherapy alone. Methods: Phase II–III trials with pathological or safety outcomes through January 2026 were included. Treatment components - CRT and ICI plus chemotherapy- were analyzed using frequentist random-effects CNMA with chemotherapy alone as a reference. Outcomes included pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and grade ≥3 adverse events (AEs). Results: Nineteen studies (n = 4,502) contributed to a connected network comparing chemoradiotherapy (CRT), ICI plus chemotherapy, and chemotherapy alone. Compared with chemotherapy alone, CRT significantly improved pathologic complete response (pCR; OR 6.53, 95% CI 4.70–9.08) and major pathologic response (MPR; OR 3.37, 95% CI 2.39–4.76), while ICI plus chemotherapy also demonstrated significant benefit for pCR (OR 3.96, 95% CI 3.05–5.15) and MPR (OR 2.51, 95% CI 1.94–3.26). R0 resection rates were significantly higher with ICI plus chemotherapy compared with chemotherapy alone (OR 1.88, 95% CI 1.08–3.26). Grade ≥3 adverse events were higher with chemoradiotherapy (OR 2.32, 95% CI 1.10–4.88) but not with ICI plus chemotherapy (OR 1.38, 95% CI 0.81–2.34). Between-study heterogeneity was moderate (I² range, 22%–67%). Conclusions: Both CRT and ICI plus chemotherapy significantly improve pathological response compared with chemotherapy alone in resectable ESCC. Although CRT achieves the greatest gains in pCR and MPR, ICI plus chemotherapy improves R0 resection and does not significantly increase grade ≥3 adverse events, supporting its favorable benefit-risk profile and emerging role as an alternative neoadjuvant strategy. Pathological and safety outcomes of chemoradiotherapy and ici plus chemotherapy. Outcome Treatment Group Odds Ratio (95% CI) P-value pCR CRT 6.53 (4.70–9.08) <0.001 pCR ICI+Chemo 3.96 (3.05–5.15) <0.001 MPR CRT 3.37 (2.39–4.76) <0.001 MPR ICI+Chemo 2.51 (1.94–3.26) <0.001 R0 Rate CRT 1.76 (0.82–3.76) 0.144 R0 Rate ICI+Chemo 1.88 (1.08–3.26) 0.025 G≥3 AEs CRT 2.32 (1.10–4.88) 0.027 G≥3 AEs ICI+Chemo 1.38 (0.81–2.34) 0.235 Abbreviations: pCR = pathological complete response; MPR = major pathological response; CRT = chemoradiotherapy; ICI = immune checkpoint inhibitor; AEs = adverse events.