Browse Articles

Baseline bone marrow biopsy (BMBx) performance relative to a mastery-level standard: A SIM-BMBx interval analysis.

9046 Background: BMBx is the gold standard diagnostic test for many pathologies. Bedside BMBx is frequently performed by advanced practice providers (APPs) and is required of Hematology-Oncology (HO) fellows by the ACGME. Apprenticeship-style instruction is inconsistent and promotes variable practice. Simulation-based mastery learning (SBML) standardizes instruction to a mastery performance standard (MPS) and is known to improve skill acquisition, retention, and performance. We developed an SBML curriculum for BMBx and herein provide a report of baseline performance. Methods: We developed a 28-item BMBx checklist based on experience, literature review, and institutional feedback. Eight experts completed a Modified Angoff Method that set the checklist MPS at 27. Maintaining sterile technique was mandatory. HO fellows, HO APPs, and Internal Medicine (IM) residents were invited to participate. Participants completed a survey of their experience and confidence in performing BMBx. Those with < 3 BMBx were considered “novice,” and those with > 3 were “experienced.” Participants completed a baseline simulated BMBx (B1) using the VATA Bonnie Bone Marrow Biopsy Skills Trainer. Performance was assessed by investigators via the checklist. The first 15 simulations were co-evaluated for consistency. The protocol was exempted by Northwestern University’s IRB. The primary endpoint is the change between B1 and post-SBML score. We performed a descriptive analysis of B1 conducted at 50% enrollment. Results: Twenty-five participants completed B1, including 10 APPs, 9 fellows, and 6 residents. Nine were novices (3 APPs, 6 residents). The 16 experienced participants (7 APPs, 9 fellows) had all performed 10 or more BMBx. The median B1 score was 17 (range 6 – 27). One participant, an APP, met the MPS at B1 with a score of 27. The median among APPs, fellows, and residents was 17 (8 – 27), 18 (15 – 23), and 8.5 (6 – 14), respectively. The median among novices was 10 (6 – 19) and among experienced was 18 (12 – 27). Baseline confidence scores were numerically higher for experienced participants (Table 1). Conclusions: For the vast majority of practitioners, regardless of professional training and experience with the procedure, BMBx performance does not meet an expert-derived MPS. Experienced practitioners have high confidence despite this. More consistent education of BMBx technique and best practices is needed and may be achieved with SBML. Participant B1 confidence scores. N ID Biopsy Site Anesthetize Site Obtain Specimen Self-Assess Performance Troubleshoot to Obtain Specimen Post-Procedure Instruction Novice 9 30 (10-70) 30 (10-60) 0 (0-50) 0 (0-50) 0 (0-50) 10 (0-80) Experienced 16 80 (0-100) 90 (0-100) 80 (0-90) 80 (0-100) 70 (0-100) 90 (10-100) Overall 25 70 (0-100) 80 (0-100) 70 (0-90) 60 (0-100) 60 (0-100) 80 (0-100) Median (range) confidence in performing an activity from 0 (very low) to 10 (very high).

National inpatient outcomes and hospital-volume disparities after glioma resection: A HCUP NIS analysis.

e14102 Background: High-quality glioma surgery requires multidisciplinary expertise, yet access to high-volume centers varies. National estimates of inpatient morbidity and resource utilization can identify actionable quality gaps and disparities. Methods: We analyzed the HCUP National Inpatient Sample (NIS) for adult admissions undergoing intracranial glioma resection from 2016–2022. Primary outcomes were in-hospital mortality and major complications (neurologic, infectious, thromboembolic, hemorrhagic). Secondary outcomes included length of stay (LOS), total charges, non-home discharge, and weekend admissions. Survey-weighted methods generated national estimates, and multivariable regression evaluated associations with hospital volume, teaching status, region, and patient-level socioeconomic variables, adjusting for age, comorbidities, and admission urgency. Results: Among 23,874 weighted admissions, in-hospital mortality was 2.1%, and major complications occurred in 14.7%. High-volume centers had lower odds of mortality (adjusted OR 0.62, 95% CI 0.51–0.75) and complications (OR 0.71, 95% CI 0.63–0.80) compared with low-volume hospitals. LOS was shorter at high-volume centers (median 5 vs 7 days, p < 0.001), with lower total charges. Patients from lower-income quartiles and rural areas had higher odds of complications and non-home discharge (OR 1.33, 95% CI 1.11–1.59). Weekend admissions were associated with modestly higher complication rates (OR 1.12, 95% CI 1.01–1.24). Conclusions: National inpatient outcomes for glioma resection vary by hospital volume and patient socioeconomic factors, highlighting disparities in access to high-quality surgical care. Clinical takeaway: Referral to high-volume centers and targeted support for vulnerable populations may reduce complications, optimize resource utilization, and improve equity in glioma surgical care.

Systemic inflammation and tumor immune microenvironment biomarkers (FOXP3, CD68, CD163) stratified by BRCA/HRD status in high-grade serous ovarian carcinoma: Associations with PFS and OS.

5546 Background: Outcomes in high-grade serous ovarian carcinoma (HGSOC) may be influenced by systemic inflammation and the tumor immune microenvironment. We evaluated the prognostic impact of systemic inflammatory markers and intratumoral immune biomarkers, including FOXP3⁺ regulatory T cells and tumor-associated macrophages (CD68 and CD163), in the context of BRCA/HRD status. Methods: We conducted a retrospective cohort study of patients with HGSOC with available baseline systemic inflammatory markers and tumor immunohistochemistry. Systemic inflammation was assessed using neutrophil-to-lymphocyte ratio (NLR >3.5) and lactate dehydrogenase (LDH >220). Intratumoral FOXP3, CD68, and CD163 expression was evaluated by immunohistochemistry. BRCA/HRD status was coded as positive versus negative. Progression-free survival (PFS) and overall survival (OS) were analyzed using multivariable Cox proportional hazards models. Results: Twenty-nine patients were included, with 27 PFS events and 25 OS events. In multivariable analysis for PFS, elevated systemic inflammation was independently associated with worse outcomes: NLR >3.5 (HR 5.88, 95% CI 1.35–25.54; p=0.018) and LDH >220 (HR 6.70, 95% CI 1.33–33.74; p=0.021). Within the tumor microenvironment, higher intratumoral CD68 was associated with inferior PFS (HR 1.10, 95% CI 1.04–1.17; p=0.001), whereas higher CD163 was associated with improved PFS (HR 0.92, 95% CI 0.87–0.97; p=0.002). BRCA/HRD positivity was not independently associated with PFS. For OS, BRCA/HRD positivity was strongly protective (HR 0.14, 95% CI 0.03–0.60; p=0.008), while NLR >3.5 remained independently associated with worse OS (HR 4.27, 95% CI 1.17–15.68; p=0.028). High FOXP3 expression was associated with improved OS (HR 0.06; p=0.032). CD68 and CD163 showed borderline associations with OS. Conclusions: In this HGSOC cohort, baseline systemic inflammation was associated with inferior PFS, and elevated NLR predicted worse OS. Intratumoral immune biomarkers showed distinct prognostic patterns, suggesting that the balance and functional state of myeloid and regulatory immune compartments influence outcomes. BRCA/HRD positivity remained strongly favorable for OS. These findings support further investigation of integrated systemic and tumor immune profiling in larger, prospectively annotated cohorts.

Assessment of the ability of Decipher Prostate Genomic Classifier (DGC) >0.85 to identify patients who benefit from adding docetaxel (DOC) to androgen deprivation therapy (ADT) plus enzalutamide (ENZ): Level 1B evidence from the ENZAMET study.

5001 Background: DGC predicts overall survival (OS) benefit from DOC when added to ADT while the benefit of adding DOC to ADT and ENZ is unknown. We hypothesized in a locked prespecified statistical analysis plan that higher GC score (> 0.85, the locked threshold on clinical test report) will identify patients who benefit from addition of DOC to ADT plus ENZ independently of metastases volume and timing. Methods: DGC scores were generated from transcriptome profiling using a clinical test (Veracyte) on tumor index cores from participants (pts) randomised on ENZAMET study (N = 1,125) 1:1 ADT with NSAA or ENZ with clinical discretion to add DOC as part of standard of care. Primary tumor samples were available from 764 pts. Differential DOC OS benefit was assessed by testing the marker-by-treatment interaction term in propensity score-weighted Cox models, with weights based on factors associated with planned DOC use. Prognostic effects of DGC were estimated using Cox for age, WHO PS, Gleason, randomized arm +/- planned DOC, metastases volume and timing, with adjusted hazard ratios (aHR) and 95% CIs. Analyses were prespecified and conducted independently by two statisticians. Results: DGC scores were available for 634 (83%) unique pts (median follow-up 5.6 years) with clinical factors representative of the overall trial. Median age was 68 yrs with 50% HV, 62% synchronous presentation, and 44% with planned DOC. Planned DOC was associated with younger age, high volume and synchronous presentation (all p≤0.002). Median DGC score was 0.88 (IQR 0.75-0.96) and 55% had DGC > 0.85 (62% in pts with DOC planned, 49% in others). Overall, higher GC was significantly associated with poorer OS (aHR 1.37 [1.06-1.78], p = 0.02). DOC benefit differed by GC level [higher vs lower] in pts treated with ADT plus ENZ (p-interaction 0.043). Higher DGC was associated with worse OS in pts treated with ADT plus ENZ (aHR 2.31 [95% CI 1.26-4.21], p = 0.007) while pts treated with DOC added to ADT plus ENZ showed no significant difference by DGC (aHR 1.08 [0.63–1.86]). Effects were more pronounced in pts with high vs. low volume disease. Conclusions: DGC > 0.85 is predictive of benefit from adding DOC to ADT plus ENZ as it negated the poor prognostic outcome of DGC > 0.85 with ADT plus ENZ alone, whereas there was no evidence of benefit for adding DOC for pts with GC ≤0.85. 5yr OS N Lower Decipher Higher Decipher Higher vs. loweradj. HR (95% CI) Overall 634 71%(66-77%) 57%(51-62%) 1.37(1.1, 1.8) ADT+ENZ 178 86%(78-93%) 62%(52-72%) 2.29(1.3, 4.2) ADT+ENZ+DOC 142 66%(53-79%) 58%(48-68%) 1.08(0.6, 1.9) ADT+ENZ (LV) 123 88%(80-96%) 72%(61-84%) 1.96(0.9, 4.3) ADT+ENZ+DOC (LV) 44 86%(67-100%) 79%(64-94%) 1.70(0.3, 9.0) ADT+ENZ (HV) 55 81%(65-96%) 41%(23-60%) 2.83(1.1, 7.5) ADT+ENZ+DOC (HV) 98 58%(42-75%) 48%(36-61%) 1.07(0.6, 1.9)

CT-derived visceral fat phenotypes to reveal a metabolically defined TOFI subgroup in a lung cancer screening cohort: An imaging-based framework for evaluating the BMI paradox.

8065 Background: Body mass index (BMI) imperfectly reflects metabolic health and cannot distinguish subcutaneous from visceral fat, contributing to the long-standing “BMI paradox” in cancer, whereby higher BMI is sometimes associated with better survival. Visceral fat is metabolically active and promotes cancer progression. Individuals with normal BMI but high visceral fat, termed “Thin Outside, Fat Inside” (TOFI) are understudied in cancer populations. These TOFI patients may represent an unrecognized high-risk metabolic phenotype in cancer. We investigated whether CT-derived lower-thoracic visceral fat identifies TOFI as a high-risk subgroup for cancer mortality. Methods: Baseline CT scans from participants in the National Lung Screening Trial (NLST; n = 19,140), a lung cancer screening cohort designed to detect NSCLC, were segmented to extract subcutaneous fat, visceral fat, and vertebral levels. Because T9–T12 best captures abdominal visceral adiposity, the percentage volume of visceral fat relative to subcutaneous fat from this region was used for phenotyping. Low (<20%) and high (>40%) visceral fat groups were defined, yielding 9,887 participants. Visceral fat was combined with BMI (<25 vs ≥25) to define four phenotypes: P1 (LowBMI_LowVIS), P2 (HighBMI_LowVIS), P3 (HighBMI_HighVIS), and P_TOFI (LowBMI_HighVIS). Cancer-specific mortality was the primary endpoint, and Cox proportional hazards models were used to compare these phenotypes. Results: Distinct phenotypes demonstrated markedly different mortality risks (Table). The TOFI group exhibited the worst survival despite normal BMI, with nearly double the cancer mortality risk compared with the metabolically favorable reference group, P1 (HR 1.95; 95% CI, 1.31-2.91; p = 8.4e-04). In contrast, high-BMI groups showed only modest or no excess risk, supporting the limitation of BMI alone. Conclusions: CT-derived visceral fat phenotyping reveals a clinically relevant high-risk group TOFI, individuals who have normal BMI but significantly elevated cancer and all-cause mortality risk compared to even high-BMI patients. This finding directly exposes the BMI paradox, showing that normal BMI does not confer protection when visceral adiposity is high. Because this TOFI phenotype is undetectable by BMI, incorporating visceral fat assessment into lung cancer screening and survivorship models could enable earlier identification of high-risk TOFI patients and guide targeted prevention. Phenotype Cancer Mortality HR (95% CI) p-value All-Cause Mortality HR (95% CI) p-value P_TOFI (LowBMI_HighVIS) 1.95 (1.31-2.91) 8.4e-04 2.42 (1.84-3.18) 7.5e-11 P3 (HighBMI_HighVIS) 1.25 (0.91-1.71) 1.7e-01 1.59 (1.27-1.98) 3.7e-05 P2 (HighBMI_LowVIS) 0.92 (0.64-1.30) 6.2e-01 1.08 (0.84-1.39) 5.4e-01 P1 (LowBMI_LowVIS) Reference - - -

Differential association of post-testosterone recovery PSA kinetics with progression and metastatic outcomes in prostate cancer.

e17122 Background: Prostate-specific antigen (PSA) kinetics following testosterone recovery from androgen deprivation therapy (ADT) may reflect heterogeneous tumor biology and distinct failure mechanisms. We evaluated the association between post-testosterone recovery PSA dynamics and progression and metastasis using Bayesian joint modeling, with sensitivity analyses accounting for competing mortality. Methods: Individual patient data were pooled from two randomized trials: (1) intermediate-risk prostate cancer treated with 6 months of neoadjuvant versus adjuvant ADT with prostate radiotherapy (RT), and (2) high-risk prostate cancer treated with 36 months of ADT with prostate and pelvic RT with 3D-CRT versus helical tomotherapy. Serial PSA measurements obtained up to 18 months after testosterone recovery to supracastrate levels (> 50 ng/dL) but before progression were analyzed using Bayesian joint models linking longitudinal mixed-effects models of log-transformed PSA with survival submodels for progression-free survival (PFS) and metastasis-free survival (MFS). Models adjusted for age, baseline PSA, Gleason score, tumor stage, and ADT duration. Associations of PSA slope and cumulative PSA exposure with event risk were estimated via shared random effects. Results: A total of 402 patients contributed 1,471 post-testosterone recovery PSA measurements. With a median follow-up of 117 months (IQR, 90-150), 167 PFS-related events and 144 MFS-related events were observed. In joint modeling, steeper PSA slope was strongly associated with higher progression risk. With approximately 1% relative increase in PSA per month - the hazard of progression or death increased by 11% (posterior median HR: 1.11; 95% credible interval [CrI]: 1.01-1.22). The association between PSA slope and MFS differed in direction (posterior median HR 0.88; 95% CrI 0.78-0.99). Cumulative PSA exposure showed no clinically meaningful association with either endpoint. In cause-specific Cox analyses censoring deaths, PSA slope remained strongly associated with progression (per approximately 1% relative increase in PSA per month, posterior median HR was 1.20 [95% CrI 1.08-1.34]), whereas its association with distant metastasis was attenuated (posterior median HR 1.00; 95% CrI 0.74-1.32). Conclusions: PSA slope after testosterone recovery is a robust marker of progression risk but has a framework-dependent relationship with metastasis. These findings indicate that post-testosterone recovery PSA kinetics should not be interpreted as a uniform surrogate of metastatic risk. Instead, PSA dynamics likely reflect failure phenotype, surveillance intensity, and clinical intervention rather than metastatic potential alone. Bayesian joint modeling provides a powerful framework for endpoint-specific interpretation of PSA behavior after RT and ADT.

Impact of RNA sequencing on diagnosis and therapy: Early results from a tertiary cancer center in India.

e23522 Background: RNA sequencing (RNA-seq) can detect gene fusions and expression-linked copy-number events that may be missed or remain ambiguous on standard workup. We evaluated the real-world clinical utility of RNA-seq specifically through fusion and amplification detection, focusing on whether results changed diagnosis and/or altered treatment. Methods: We reviewed consecutive patients undergoing RNA-seq at our center. Utility endpoints were captured prospectively/retrospectively in the dataset as (1) diagnosis change owing to RNA-seq and (2) treatment-course change owing to RNA-seq. For this analysis, RNA-seq “unique yield” was defined as fusion and/or amplification reported. Outcomes were summarized overall and by sarcoma/mesenchymal vs other cancers. Results: Among 26 evaluable patients, RNA-seq identified fusions and/or amplifications in 13/26 (50.0%) (fusions: 12/26 [46.2%]; amplifications: 3/26 [11.5%]). Diagnosis changed owing to RNA-seq in 4/26 (15.4%), and all diagnosis-changing cases were fusion-driven (4/4). Treatment-course change attributable to RNA-seq was documented in 6/25 (24.0%) patients with evaluable treatment-impact data. Fusion/amplification yield was higher in sarcoma/mesenchymal tumors (8/14 [57.1%]) than in other cancers (5/12 [41.7%]). Diagnosis change owing to RNA-seq occurred in 3/14 (21.4%) sarcoma/mesenchymal cases and 1/12 (8.3%) other cancers; treatment change owing to RNA-seq was observed in 3/13 (23.1%) vs 3/12 (25.0%), respectively. Conclusions: In this real-world cohort, RNA-seq demonstrated meaningful clinical utility primarily through fusion/amplification detection, with 15.4% diagnosis changes and 24.0% treatment changes attributable to RNA-seq. Impact was enriched in fusion/amplification-positive cases, supporting RNA-seq as a high-value adjunct test—particularly in diagnostically challenging sarcoma/mesenchymal tumors and selected carcinomas. Diagnosis change owing to RNA-seq (fusion-driven). Case Pre-RNA working diagnosis Histopathology Key RNA-seq finding (fusion/amp) Post-RNA integrated diagnosis / implication (as recorded) 1 Metastatic adenocarcinoma, CUP Adenocarcinoma FGFR–FILIP1 fusion Likely cholangiocarcinoma (site-of-origin reclassification) 2 Atypical teratoid / rhabdoid tumor ATRT, metastatic SS18–SSX2 fusion (t(18;X)) Fusion-consistent synovial sarcoma biology → diagnostic reclassification 3 Spindle cell tumor (low malignant potential; SMC differentiation) Spindle cell tumor (low malignant potential; SMC differentiation) LRRFIP1–ALK fusion ALK-rearranged IMT biology confirmed → diagnostic refinement/reclassification 4 Tenosynovial giant cell tumor (TGCT) Spindle cell tumor (intermediate malignant potential; myogenic differentiation) RRBP1–USP6 fusion Nodular fasciitis (benign) → diagnosis changed to benign entity

Assessment of racial and age disparities in response and survival among acute myeloid leukemia (AML) patients treated with hypomethylating agents (HMA) and venetoclax.

e18619 Background: Venetoclax combined with an HMA has improved outcomes for older or cytotoxic chemotherapy-ineligible AML patients. Historically, intensively treated non-Hispanic black (NHB) and older patients have worse survival. To what extent these disparities are seen with venetoclax and HMA is not known. Methods: We conducted a retrospective cohort study of 184 newly diagnosed adults treated with HMA and venetoclax between January 2018 and the present at our cancer center. Outcomes were examined by race and age (<70 vs ≥70 years). Data collected included demographics, performance status, comorbidities, cytogenetics, molecular mutations, and risk stratification per ELN 2024 criteria. Endpoints were overall survival (OS), 30-/60-day mortality, and response according to ELN 2022 criteria. Results: Of 184 patients, 21 were NHB and 163 were non-Hispanic White (NHW). NHB patients were younger (66 vs 73.8 years, p = 0.0011) and more likely to have Medicaid (28.6% vs 3.1%, p < 0.0001). Median OS was 6.9 months for NHB versus 8.3 months for NHW (log-rank p = 0.3662). Response differed significantly ( p = 0.0136): CR 9.5% (NHB) vs 4.3% (NHW), CRi 23.8% vs 33.7%, and MLFS 33.3% vs 21.5%. Of the 184 patients, 53 were younger than 70 at the time of AML diagnosis and 131 were 70 or older. Older patients were more likely to have Medicare (47.2% vs 84%, p < 0.0001). Median OS was 7.2 months for younger patients versus 8.4 months for the older group (log-rank p = 0.1275); the difference was not statistically significant, but Kaplan-Meier curves show separation after 6 months. Response trended toward significance ( p = 0.0574): CR 9.4% (<70) vs 3.1% (70+), CRi 22.6% vs 36.6%, and MLFS 30.2% vs 19.8%. Conclusions: OS did not differ significantly by race or age, but response patterns varied. While not significantly different, Kaplan-Meier curves suggest a trend toward decreased OS among NHB and younger patients. Our limited sample size from a single institution reduces the ability to draw definitive conclusions. However, older patients demonstrated a numerically superior OS; historically, worse outcomes have been observed in older patients when treated with intensive chemotherapy. Additionally, NHB patients demonstrated a numerically lower OS, however significantly superior rates of CR. Future research incorporating larger, multi-institutional cancer centers is needed to confirm these results.

Global mortality and disability burden of young-onset non-colorectal gastrointestinal cancers, 1990–2021.

e16476 Background: The incidence of gastrointestinal (GI) cancers among adults younger than 50 years has risen worldwide. While trends in early-onset colorectal cancer (CRC) are well documented, the burden of non-colorectal GI malignancies in younger populations remains poorly characterized across sociodemographic contexts. Methods: Using Global Burden of Disease (GBD) 2021 data, we quantified mortality and disability-adjusted life-years (DALYs) for gastric, liver, pancreatic, gallbladder/biliary, and esophageal cancers among individuals aged 15–49 years from 1990–2021. Age-standardized mortality rates (ASMRs) and DALY rates were evaluated across socio-demographic Index (SDI) quintiles. Temporal trends were assessed using linear regression to estimate average annual percent change (AAPC) with corresponding 95% confidence intervals. Results: From 1990–2021, young-onset non-colorectal GI cancers caused 7,311,542 deaths globally, led by gastric (3,203,746; 43.8%), liver (1,874,358; 25.6%), and esophageal cancers (1,223,473; 16.7%). Gastric cancer contributed 3,203,746 deaths, with the highest DALY burden (147.9; 95%CI:128.5–163.3), global ASMR 3.0 (95%CI:2.6–3.3), and peak mortality in high-middle SDI regions (ASMR 3.2; 95%CI:2.6–3.7); both mortality and DALYs declined over time. Liver cancer accounted for 1,874,358 deaths (ASMR 1.7; 95% CI:1.6–1.9; DALYs 85.6; 95% CI 77.9–94.8), with highest mortality in the high-middle (ASMR 2.2; 95% CI 1.8–2.7) and middle SDI regions (2.0; 95% CI 1.7–2.5) and increasing mortality in low-middle SDI regions (AAPC 0.3; 95% CI 0.2–0.4). Esophageal cancer caused 1,223,473 deaths (ASMR 1.1; 95% CI 1.0–1.2; DALYs 54.1; 95% CI 49.6–58.7), with highest mortality in high-middle SDI regions (ASMR 1.3 95% CI 1.0–1.6) and overall global declines. Pancreatic cancer mortality increased globally (AAPC 0.1; 95% CI 0.1–0.2), driven by sharp rises in low-middle SDI regions (AAPC 1.6; 95% CI 1.6–1.6) and middle SDI regions (1.2; 95% CI 1.1–1.3), and showed the highest mortality in high-middle (ASMR 1.4; 95% CI 1.2–1.6) and high SDI regions (1.1; 95% CI 1.0–1.2), with DALYs 32.9 (95% CI 31.2–34.7). Gallbladder and biliary cancers had the lowest burden (DALYs 11.4; 95% CI 9.0–12.8), but mortality increased in low-middle (AAPC 0.6; 95% CI 0.5–0.6) and middle SDI regions (AAPC 0.2; 95 %CI 0.1–0.2). Conclusions: Substantial increases in young-onset pancreatic and hepatobiliary cancer mortality in lower-middle SDI regions reflect shifting global epidemiology. Geographic disparities in gastric, liver, and pancreatic cancer burdens highlight the need for targeted prevention and improved early detection strategies beyond colorectal cancer. AAPC in age-standardized mortality rates by SDI region. Cancer Type High SDI High-middle SDI Middle SDI Low-middle SDI Low SDI Stomach ↓ ↓ ↓ ↓ ↓ Esophageal ↓ ↓ ↓ ↓ ↓ Liver ↓ ↓ ↓ ↑ ↓ Pancreatic ↓ ↑ ↑ ↑↑ ↑ Gallbladder/Biliary ↓ ↓ ↑ ↑ ↓

Hi-C sequencing to identify clinically actionable fusions in non–small cell lung cancer missed by other sequencing technologies.

8630 Background: For a patient with non-small lung cancer (NSCLC) to benefit from targeted therapy, an actionable driver alteration needs to be identified. DNA-based next-generation sequencing (NGS) is the standard across many clinical laboratories, however, there are known limitations in the detection of structural rearrangements. RNA-based NGS is now being increasingly utilized in cases with negative DNA NGS testing, but it is currently unknown how many driver alterations are missed with RNA NGS. Hi-C, high-throughput chromosome conformation capture, is a newer NGS method that can be performed on formalin-fixed paraffin-embedded (FFPE) tissue to detect pairwise interactions between DNA regions and may have increased sensitivity for fusion detection. Methods: We collected FFPE tissue from NSCLC cases that were previously deemed to be negative for driver mutations through standard DNA and/or RNA based NGS. We performed Hi-C sequencing on these samples with the Arima Aventa FusionPlus test. This involves digestion of DNA in situ followed by religating to nearby DNA regions and sequencing pairs of DNA tags that reveal proximal DNA sequences. RNA-Sequencing was performed via multiple commercial testing labs using either panel based or whole transcriptome sequencing. Results: In 118 NSCLC specimens that were negative on prior NGS testing, 6 samples (5%) tested positive on Hi-C sequencing for a clinically actionable alteration, including 5 samples that were negative with both DNA and RNA-based NGS. Among these 6 samples were 5 cases of NRG1 fusions and one case of an NTRK2 fusion. All cases with NRG1 fusions have breakpoints proximal to exon 2 and therefore are expected to have expression of the full EGF-like domain. RNA-Sequencing of several of these cases confirmed high expression of NRG1. As an example, one patient had prior negative sequencing with tissue-based panel DNA NGS, ctDNA NGS, an RNA fusion panel, and whole transcriptome RNA-Seq. This patient’s Hi-C sequencing identified a non-canonical NRG1 fusion with an intergenic region fused upstream of exon 2 of NRG1. After progression on chemo-immunotherapy, the patient was treated with zenocutuzumab, a recently approved bispecific antibody that blocks NRG1 from activating HER2/HER3 signaling. A CT Chest scan 6 weeks after initiation showed near complete resolution of the diffuse miliary metastases. Conclusions: Hi-C can identify clinically actionable driver alterations in NSCLC cases that were negative on other sequencing tests, highlighting the potential value of incorporating this technology into clinical practice.

Real-world utilization and survival trends of adjuvant immunotherapy in postoperative stage II-III non-small cell lung cancer: A Louisiana population-based study.

e20072 Background: Currently adjuvant immunotherapy (AI) is standard of care for patients with resectable non-small cell lung cancer (NSCLC). While clinical trials have established the efficacy of AI, real-world evidence remains limited. This study aimed to evaluate the real-world adoption of AI and its survival benefits in patients with postoperative stage II-III NSCLC using a population-based data. Methods: We analyzed data from the Louisiana Tumor Registry (LTR) for patients diagnosed with stage II-III NSCLC between 2015 and 2023 who underwent definitive surgery. Survival curves were estimated using the Kaplan–Meier method. Multivariable Cox proportional hazards models were employed to assess overall survival (OS), adjusting for sociodemographic factors (age, race, sex, insurance, marital status), clinical variables (stage, grade, tumor number, comorbidities), and treatment (chemotherapy, radiation). Results: This study enrolled 1,473 patients with a mean age of 66.17±9.14 years and median follow-up of 36 months. Of these, 186 (12.63%) received AI, with 51 (27.42%) deaths during follow-up. Kaplan-Meier survival estimates demonstrated that the AI group achieved superior overall survival compared to the non-AI group during the initial three years of follow-up. period. After adjusting for important confounders, the AI group had lower mortality risk compared to the non-AI group, although this did not reach statistical significance (aHR = 0.778; 95% CI = 0.580–1.044, p = 0.094). Additionally, race and marital status were not significantly associated with survival outcomes in the Cox model. However, female sex (aHR: 0.749, p = 0.0004) and having Medicaid insurance (HR: 1.276, p = 0.0463) were identified as significant independent predictors of survival. Conclusions: AI may provide survival benefits for postoperative stage II-III NSCLC patients in a real-world setting. More real-world data with larger sample size and longer follow-up periods would be warranted.

Comparative analysis of temperature effect on bandgap characteristics in 1D phononic crystals: Periodic versus quasiperiodic structures

Phononic crystal-based sensors have emerged as highly promising platforms for precise temperature monitoring due to their ability to manipulate acoustic wave propagation through engineered bandgaps. In this work, a 1D phononic crystal composed of alternating layers of tungsten and polycrystalline silicon is systematically investigated in both periodic and quasiperiodic configurations. The study aims to comparatively evaluate periodic and quasiperiodic architectures- including Fibonacci, Thue-Morse, double-periodic, and Cantor sequences, to identify an optimal structural arrangement that maximizes bandgap width and enhances sensing performance. The simulation upshots revealed that the Fibonacci quasiperiodic configuration exhibits the widest Phononic band gap, reaching 18 × 10 6 Hz at an operating temperature of 373 K. Meanwhile, the sensor performance is assessed in terms of temperature sensitivity, where the periodic structure demonstrates a stable and linear response over the investigated temperature range, with a maximum sensitivity of 62.5 Hz/K at 373 K. To evaluate practical feasibility, fabrication tolerances are incorporated by considering up to 5% deviations and material property disorders. Additionally, Monte Carlo simulations are employed to analyze the robustness of the transmission spectrum under such uncertainties. In this regard, the investigated results highlight the trade-off between enhanced bandgap characteristics in quasiperiodic structures and the superior stability of periodic configurations, providing valuable insights for the design of high-performance phononic crystal sensors.

Concerted Proton and Electron Transfer in Heterogeneous Electrocatalytic CO ₂ Reduction

ABSTRACT Understanding how protons influence heterogeneous electrocatalytic CO 2 reduction on electrode surfaces is critical for advancing energy‐efficient carbon conversion technologies. Here, we show that on Ag, Au, and Zn surfaces, a concerted proton‐electron transfer (CPET) pathway enables CO 2 ‐to‐CO conversion at up to ∼400 mV lower overpotential than commonly proposed cation‐stabilized mechanisms, which dominate reactivity at higher overpotentials. Using both positively charged and neutral proton donors, we show that CPET operates at low overpotentials but is limited by the rate of proton supply. Kinetic isotope effect measurements and infrared adsorption spectroscopy support the involvement of protons in the rate‐determining step. Furthermore, our data shed light on the complex competition for proton donors between CO 2 reduction, carbonate acidification, and hydrogen evolution, explaining commonly reported product trends. Our findings suggest that enhancing proton flux and suppressing the hydrogen evolution reaction can further promote CPET‐based CO 2 reduction, offering a pathway to more efficient electrocatalytic processes.

Effect of calcination temperature on the magnetic and biological behavior of green tea-assisted NiFe₂O₄ nanoparticles

A rule-based mobile screening classifier for six ICVD-defined vestibular disorders: a pilot study

Ubiquitin E3 ligase MYCBP2 targets KIF14 and contributes to acute myeloid leukemia progression

Knowledge of HPV-related penile cancer among U.S. men: Socioeconomic differences and divergence.

e17034 Background: Human papillomavirus (HPV) is a well-established cause of penile cancer, yet awareness of this association among U.S. men remains poorly defined, particularly across sociodemographic groups. Methods: We analyzed pooled cross-sectional data from the National Cancer Institute’s Health Information National Trends Survey (HINTS 5, Cycles 1-4), a nationally representative survey using two-stage stratified sampling of U.S. adults aged ≥18 years. Analyses were restricted to male respondents. The primary outcome was lack of knowledge that HPV can cause penile cancer (responding “no” or “not sure” vs “yes”). Survey-weighted multivariable logistic regression estimated adjusted odds ratios (aORs) for sociodemographic predictors, including age, race, marital status, education (≤high school as reference), income ( < $35,000 as reference), sexual orientation, and cancer history. All analyses accounted for complex survey design using jackknife replicate weights per HINTS methodology. Results: Among 3,211 U.S. men (median age 55 years), only 31% correctly identified HPV as a cause of penile cancer. Education and income demonstrated divergent associations with knowledge. Compared with men with a high school education or less (n = 461), college graduates (n = 987; aOR 0.74, 95% CI 0.56-0.97) and those with postgraduate education (n = 784; aOR 0.59, 95% CI 0.45-0.79) had lower odds of lacking knowledge of HPV-related penile cancer. In contrast, compared with men with annual income < $35,000 (n = 563), those with middle income ($35,000- < $100,000; n = 1,364; aOR 1.69, 95% CI 1.30-2.19) and high income (≥$100,000; n = 1,143; aOR 1.60, 95% CI 1.23-2.08) had greater odds of lacking knowledge. Sexual orientation was not independently associated with knowledge after adjustment. Conclusions: Knowledge that HPV causes penile cancer remains low among U.S. men. While higher educational attainment was associated with greater awareness, higher income was paradoxically associated with lower awareness, highlighting that commonly used socioeconomic indicators may not uniformly reflect HPV-specific cancer knowledge. The observed discordance between income and education suggests that higher income alone does not confer improved HPV- related cancer awareness, underscoring the need for male-focused HPV education and prevention strategies that are not solely targeted by traditional socioeconomic markers.

Quality of life outcomes following hypofractionated radiotherapy in locally advanced cervical cancer.

5534 Background: Cervical cancer remains a significant global health burden, particularly in low- and middle-income countries where access to radiotherapy is often limited. While concurrent chemoradiotherapy is the standard of care, hypofractionated radiotherapy has emerged as a potential strategy to improve treatment efficiency without compromising outcomes. Our purpose was to assess the impact of hypofractionated radiotherapy on quality of life in comparison with conventional fractionation in patients with locally advanced cervical cancer. Methods: Health-related quality of life was evaluated using EORTC QLQ-C30 and QLQ-CX24 questionnaires in patients with FIGO stage IB3–IIIC1 cervical cancer enrolled in a phase II randomized trial. All patients received concurrent chemotherapy and were assigned to either standard external-beam radiotherapy (50 Gy in 25 fractions) or hypofractionated radiotherapy (37.5 Gy in 15 fractions), followed by radical hysterectomy with bilateral pelvic lymphadenectomy. QoL scores were calculated using standard EORTC methodology. Higher scores indicate better functioning or greater symptom burden, and changes were interpreted based on established thresholds for clinical relevance. Outcomes were compared between groups across predefined time points using ANOVA. Statistical significance was defined as p < 0.05. Results: A total of 91 patients were included (49 standard fractionation, 42 hypofractionation). No significant differences in global QoL were observed between treatment groups. However, QoL varied significantly over time, with the greatest deterioration occurring between completion of concomitant chemoradiotherapy and surgery. Quality-of-life scores recovered to baseline levels by three months after treatment completion in both groups. Conclusions: Hypofractionated radiotherapy was not associated with worse quality-of-life outcomes compared with conventional fractionation. These findings support hypofractionation as a feasible alternative for locally advanced cervical cancer, particularly in resource-limited settings. Further studies with larger cohorts and longer follow-up are warranted to confirm these results. Clinical trial information: NCT03750539 . Comparison of key health-related quality-of-life domains by treatment arm. Domain BaselineStd*/ Hypo& End QT/RTStd / Hypo Post-SurgeryStd / Hypo 3 MonthsStd / Hypo p value Global Health Status / QoL 66.9 (23.7) / 65.8 (21.0) 65.7 (20.7) / 64.6 (17.0) 70.5 (18.5) / 64.0 (18.3) 79.1 (12.5) / 74.4 (21.7) 0.497 Physical Functioning 81.6 (19.7) / 88.0 (14.6) 80.2 (18.6) / 82.2 (20.8) 75.2 (20.5) / 79.0 (17.5) 86.4 (19.4) / 86.8 (13.6) 0.216 Nausea and Vomiting 87.1 (21.2) / 83.8 (27.8) 72.4 (30.5) / 67.2 (28.5) 82.6 (23.3) / 88.3 (21.0) 94.8 (10.2) / 91.1 (16.8) 0.001 Diarrhea 90.1 (15.5) / 86.6 (28.5) 77.7 (20.6) / 67.7 (28.3) 81.4 (21.3) / 84.4 (25.8) 92.5 (14.1) / 91.1 (14.9) 0.001 Mean (SD) scores using EORTC QLQ-C30 and CX-24.

Association of pre-treatment hemoglobin level as a prognostic factor for survival outcomes in head and neck cancer patients treated with definitive radiation.

e18114 Background: Anemia may be associated with worse clinical outcomes in patients with head and neck squamous cell carcinoma (HNSCC), which may be related to tumor hypoxia and decreased sensitivity to radiation therapy. However, the prognostic role of baseline hemoglobin (Hgb) is not well established. To build on prior evaluations of Hgb cutoff values, we examined the association between baseline Hgb and clinical outcomes in patients with HNSCC who were treated with definitive radiation-based therapy. Methods: We conducted a retrospective analysis of patients with HNSCC who were treated with definitive radiation therapy, with or without chemotherapy, at The Ohio State University Comprehensive Cancer Center between 2011 and 2023. Baseline Hgb was categorized using a data-driven cutoff of 12.9 g/dL, and Cox proportional hazard regression was conducted to derive the effect of Hgb on overall (OS) and progression-free (PFS) survival with consideration for outcome-model covariates. Nearest-neighbor propensity score matching and subclass-stratified Cox regression were utilized to control for confounding variables. Factors contributing to low Hgb were then identified via multivariable logistic regression. Results: Stratified survival analysis found low Hgb was associated with worse OS (aHR 2.09, 95% CI 1.26–3.48; p < 0.01) and PFS (aHR 1.96, 95% CI 1.25–3.10; p < 0.01). Prognostic, multivariable covariate regression reported low baseline Hgb was associated with worse OS (aHR 1.49; p < 0.05) but not PFS (aHR 1.29 ; p = 0.12). Additional factors independently associated with worse OS and PFS included ECOG performance status ≥1 (OS aHR 1.89, p < 0.001; PFS aHR 1.63, p < 0.001) and age ≥65 (OS aHR 1.51, p < 0.05; PFS aHR 1.60, p < 0.01), while HPV-positive disease was associated with significantly improved survival outcomes (OS aHR 0.37, p < 0.001; PFS aHR 0.37, p < 0.001).. Male sex and nodal involvement was also associated with worse survival in multivariable analyses. Conclusions: In this retrospective study, a higher baseline Hgb was associated with improved overall survival in patients with HNSCC treated with definitive radiation therapy. This finding was consistent across in propensity score–matched analyses and regressions of relevant covariates. These findings support baseline Hgb as a readily available prognostic biomarker. This study provides additional data on baseline Hgb cutoffs that may help inform clinically relevant thresholds for patients with HNSCC undergoing definitive radiation-based therapy.

Spatial transcriptomics-guided pathology biomarker as a predictor of benefit of adjuvant docetaxel in high-risk localized prostate cancer: NRG/RTOG 0521 (NCT00288080).

5111 Background: The NRG/RTOG 0521 trial evaluated adding adjuvant docetaxel (DTX) to standard radiotherapy plus androgen deprivation therapy (ADT) in high-risk localized prostate cancer. Adjuvant DTX modestly improved overall survival (OS) in the trial, but the benefit was limited and not all patients benefited. Thus, biomarkers are needed to identify patients most likely to benefit from chemotherapy intensification. ST-DoxPCa (Spatial Transcriptomics–Guided Docetaxel Therapy Stratification in Prostate Cancer) is a novel artificial intelligence (AI) driven histology biomarker that predicts gene expression from H&E slides (virtual spatial transcriptomics). We assessed whether ST-DoxPCa can stratify patients in RTOG 0521 for differential benefit from adjuvant DTX. Methods: A Vision Transformer trained on paired histology–spatial transcriptomics (HEST1K) predicts a 208-gene prostate panel at spot level; predictions are distilled into a biologically informed 26-gene signature and aggregated into patient-level features. A prognostic Cox model and fixed median threshold were developed independently in a Cleveland Clinic radical prostatectomy cohort (CCF, n=352; endpoint: biochemical recurrence-free survival). This locked model and threshold were applied unchanged (no refitting or recalibration) to digitized pretreatment diagnostic biopsies from NRG/RTOG 0521 (n=350; RT+ADT n=169, RT+ADT+DTX n=181) to stratify patients into ST-DoxPCa-positive (high-risk) and ST-DoxPCa-negative (low-risk) groups. Overall survival (OS) was compared between treatment arms within each stratum. Results: ST-DoxPCa stratified patients into biomarker-defined risk groups using aggregated spatial-expression features from a biologically informed gene panel; key genes included PTEN, NKX3-1, ACPP, FASN and TMPRSS2. ST-DoxPCa-positive (high-risk) patients experienced a significant OS benefit from adding DTX to RT+ADT versus RT+ADT alone (HR=0.38, 95% CI 0.18–0.83; p=0.012), whereas ST-DoxPCa-negative (low-risk) patients derived no OS benefit (HR=1.05, 95% CI 0.67–1.63; p=0.84). Conclusions: The ST-DoxPCa model identified a subgroup with substantial OS benefit from adjuvant DTX and a subgroup with no benefit within RTOG 0521, supporting risk-aligned chemotherapy intensification using routine histology. Clinical trial information: NRG/RTOG 0521 ( NCT00288080 ) .