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Incidence and prognostic impact of recurrence in esophageal carcinoma patients achieving complete pathological response after neoadjuvant chemoradiotherapy or perioperative chemotherapy.
4069 Background: Esophageal carcinoma remains a global challenge, ranking 7th in cancer-related mortality. While the CROSS trial established neoadjuvant chemoradiotherapy (nCRT) as a standard of care with a 29% pathological complete response (pCR) rate, real-world data in diverse histological populations—particularly Squamous Cell Carcinoma (SCC)—are evolving. We aimed to evaluate the impact of pCR on Overall Survival (OS) and Disease-Free Survival (DFS) in a high-volume surgical cohort. Methods: A retrospective analysis of a prospective database was conducted for patients undergoing curative-intent esophagectomy at a tertiary cancer center (2019–2023). Inclusion: Patients receiving neoadjuvant therapy (nCRT or perioperative chemotherapy). Exclusion: Patients with upfront surgery, palliative resections, or incomplete records. Survival outcomes were analyzed using Kaplan-Meier curve. Results: Of 546 patients, 51% were male with a mean age of 44 ± 9 years. nCRT was the primary neoadjuvant modality (92.3%), followed by perioperative chemotherapy (7.7%). pCR was achieved in 54.8% of patients. At a median follow-up of 5 years, the overall recurrence rate was 27.1%; notably, only 28.3% of the pCR group experienced recurrence compared to the non-pCR group (p < 0.001). Recurrence patterns distant (48.6%), followed by locoregional (44.6%), and both (6.8%). The pCR group demonstrated superior survival outcomes: Mean OS: 57 ± 0.7 months vs 52 ± 1 months in non-pCR (p = 0.001); Mean DFS: 52 ± 1 months vs 35 ± 1 months in non-pCR (p < 0.001). Total study mortality was 8.4%. Conclusions: In this large South Asian cohort, pCR was achieved in over half of the patients following neoadjuvant therapy and served as a robust predictor of both OS and DFS. These findings reinforce pCR as a critical surrogate endpoint for long-term oncological success and suggest that tumor biology in this region may be particularly sensitive to multimodality protocols. Clinical characteristics and survival outcomes. Variable Value (n=546) Tumor Location Distal Esophagus: 52.6%Mid Esophagus: 25.3%Gastroesophageal Junction: 12.6% Histology Squamous Cell Carcinoma (SCC): 85.7%Adenocarcinoma: 14.3% Neoadjuvant Therapy Chemoradiotherapy (nCRT): 92.3%Chemotherapy: 7.7% Surgical Procedure McKeown Esophagectomy: 78.6%Ivor Lewis Esophagectomy:18.7%Trans-hiatal Esophagectomy: 2.7% Pathological Stage (TNM)I/II/III/IV 69.5% / 10.5% / 16.6% / 3.4% Resection Margin R0 (Negative): 95.1%R1 (Microscopic Positive): 4.9% Pathological Complete Response (pCR) Overall: 54.8%Squamous cell Carcinoma: 95.3%Adenocarcinoma: 4.6% Recurrence Overall Rate: 27.1%Recurrence within PCR group: 7.6% Overall Survival (Months) pCR = 57±0.7Residual Disease = 52±1 monthsp=0.001 Disease-Free Survival (Months) pCR = 52±1Residual Disease = 35±1p= <0.001
Landscape of actionable genomic alterations in primary versus metastatic lesions from Chinese lung adenocarcinoma patients.
e20055 Background: Precision therapy improves outcomes in lung adenocarcinoma (LUAD) but requires accurate detection of actionable genomic alterations. Existing evidence demonstrates distinct genomic profiles between primary and metastatic LUAD. This real-world study systematically compared the landscape of actionable gene alterations between primary and metastatic lesions from Chinese LUAD patients. Methods: Chinese LUAD patients who had DNA-NGS testing were retrospectively enrolled. They were divided into the primary group and metastatic group based on sample source. The Chi-square test was performed to analyze differences in the prevalence of alterations (including mutations, amplifications, and fusions) in actionable genes ( EGFR, BRAF, KRAS, HER2, ALK, ROS1, RET, MET, NGR1, and NTRK ) between cohorts. Statistical significance was defined as p<0.05. Results: Two independent cohorts were established, with 3781 primary tumor samples and 424 metastatic tumor samples. The primary cohort had a mean age of 60.49 years (44.5% male; 55.5% female), and the metastatic cohort had a mean age of 62.4 years (55.2% male; 44.8% female). Mutations: EGFR and HER2 mutation rates were significantly lower in metastases ( EGFR : 50.94% vs 60.49%, p<0.001; HER2 : 3.54% vs 6.08%, p<0.05). No significant differences were observed for BRAF (4.7% vs 4.6%, p=0.89), KRAS (13.9% vs 11.0%, p=0.08), or MET (5.0% vs 3.9%, p=0.29). Amplifications: EGFR and MET amplification rates were significantly higher in metastases ( EGFR : 13.21% vs 6.06%, p<0.0001; MET : 5.42% vs 1.06%, p<0.001). HER2 amplification showed no significant difference (1.65% vs 1.16%, p=0.38). Fusions: ALK and ROS1 fusion rates were significantly higher in metastases ( ALK : 7.78% vs 5.32%, p<0.05; ROS1 : 3.77% vs 1.14%, p<0.0001). No significant differences were found for MET (0.2% vs 0.3%, p=0.91), NRG1 (0% vs 0.4%, p=0.18), FGFR (0.2% vs 0.5%, p=0.48), RET (2.6% vs 2.3%, p=0.65), or NTRK (0.2% vs 0.3%, p=0.91). Collectively, the overall rate of gene alterations analyzed above was significantly lower in metastases versus primary tumors (86.08% vs 89.55%, p<0.05). Conclusions: The landscape of actionable genomic alterations differs between metastatic and primary tumors in LUAD. This may be attributed to the intrinsic demographic factors (such as age and sex) within the two cohorts. Additionally, tumor evolution, clonal selection, and tumor heterogeneity may also partially explain these differences. The findings suggest that re-biopsy of metastatic lesions is crucial when patients experience disease progression, especially oligo-progression.
Single Crystals of Perylene Diimide‐Based Two‐Dimensional Covalent Organic Frameworks
ABSTRACT Two‐dimensional covalent organic frameworks (2D COFs) are crystalline porous polymers with highly tunable structural and electronic properties. Although single crystals of these materials are highly desirable for fundamental research and potential applications, their synthesis has so far been limited to only a few examples. We have developed a high‐temperature double‐modulator synthetic strategy that enables the growth of single crystals from fully dissolved precursors. We applied this approach to generate a series of perylene diimide (PDI)‐based 2D COFs. These materials crystallize as platelets with lateral dimensions reaching up to 50 µm for the biphenyl‐linked PDI(Me) 8 ‐2P COF, providing a suitable platform for studying electronic processes via micro‐spectroscopy. Photoluminescence (PL) measurements revealed ultrafast monomer‐like emission together with a slower excimer‐related component. The availability of COF single crystals further enabled polarization‐dependent measurements, which revealed that the fast PL component is linearly polarized due to the parallel orientation of the PDI chromophores in the frameworks. These findings highlight the importance of COF single crystals for elucidating structure—photophysical property relationships of these intriguing materials.
Pt Atomic Chain: Local Asymmetry One‐Dimensional Array for Enhanced Electrochemical Reactions
ABSTRACT Atomically dispersed arrays enhance the intrinsic catalysis activity of isolated atoms by synergistic effects. However, uneven charge distribution limits the formation of local asymmetric structures within the array, making it difficult to break the linear proportional relationship in complex multi‐intermediate chemical reactions. Here, by creating ordered in‐plane vacancies in the Mo 1.33 C surface to induce a looser lattice skeleton and then promoting the in situ substitution of Mo by Pt atoms, we report a locally asymmetric 1D sawtooth‐shaped Pt atomic chain (Pt AC). The bridging sites within this asymmetric structure reduce the energy barriers for hydrolysis and intermediate adsorption, allowing Pt AC to show superior hydrogen evolution reaction (HER) activity (12.52 A mg Pt −1 ) than isolated Pt single atoms (Pt SA, 1.32 A mg Pt −1 ) and commercial Pt/C (0.18 A mg Pt −1 ). In addition, the three‐fold hollow sites in the asymmetric structure are prone to adsorb and oxidize dopamine (DA), which is key to triggering the high sensing performance of Pt AC. Pt AC has much higher sensitivity (0.1–1 µ m : 19.5 µA µM −1 and 1–100 µ m : 1.6 µA µM −1 ) compared to Pt SA. This work opens a door for the development of atomically dispersed arrays with asymmetric structures for surface chemistry applications.
Patterns of high-risk HPV positivity in Janakpur, Nepal: Implications for scalable cervical cancer screening.
e13632 Background: Cervical cancer prevention in Nepal is constrained by the absence of a national HPV vaccination program and low uptake of opportunistic screening. Scalable, point-of-care high-risk HPV (HrHPV) testing may improve screening access in resource-limited settings. Methods: We conducted HrHPV screening using the AmpFire HPV Screening Assay among women from two communities in Janakpur, Nepal - Kapileshwar (Ward 16) and Mahua (Ward 18). Associations between HrHPV positivity and sociodemographic characteristics, cervical cancer awareness, procedural knowledge, healthcare decision-making, and information sources were examined. Of 293 enrolled participants, 274 valid tests were obtained. Multivariable logistic regression was performed among participants with valid samples. Genotype results were summarized among HrHPV-positive tests as single-type infection vs coinfection and categorized as HPV16, HPV18/45, Group A and Group B. Results: Overall HrHPV positivity was 11.7% (32/274), with positivity rates in Kapileshwar at 16.5% and in Mahuwa at 9.0%. HPV16 was the most prevalent genotype, detected in 56.3% of infections (n = 18; 14 single infections and 4 coinfections). Coinfections were detected in 18.8% (6/32) of HrHPV-positive women. In multivariable analysis, residence in Mahuwa was associated with lower odds of HrHPV positivity compared with Kapileshwar (aOR = 0.39, 95% CI 0.16 - 0.93; p = 0.033). HrHPV positivity was also higher among women lacking procedural knowledge of vaginal sample collection (p = 0.019) and among those relying on informal rather than formal information sources (p = 0.018), particularly in Kapileshwar. Conclusions: HrHPV prevalence varied across Janakpur, with higher rates in Kapileshwar and a predominance of HPV16, including coinfections. Positivity was greater among women lacking procedural knowledge and those relying on informal information sources, highlighting the importance of targeted education and clear communication. These findings support the use of point-of-care HrHPV testing combined with practical counseling to improve screening readiness and follow-up in high-risk populations. Keywords: High-risk HPV (HrHPV), AmpFire, HPV16, Genotype distribution, Coinfection, Point-of-care testing, Procedural knowledge, LMIC HrHPV Subtype distribution. Subtype Category n % HPV 16 (Single Infection) 14 43.8% Other HrHPV Group A (39/51/56/59/68) 7 21.9% Other HrHPV Group B (31/33/35/52/58) 4 12.5% Coinfection: HPV 16+Group B 3 9.4% Coinfection: HPV 16+Group A 1 3.1% Coinfection: Groups A+B 1 3.1% HPV 18/45 (Single Infection) 1 3.1% Triple Coinfection: HPV 18/45+Group A+B 1 3.1% Total 32 100%
From relative risk to lives lost: Meta-analysis–based projection of invasive fungal infection burden attributable to systemic corticosteroids.
e18624 Background: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients with hematologic malignancies. Although meta-analyses identify systemic corticosteroid exposure as a strong relative risk factor for IFI, the absolute burden attributable to corticosteroids across heterogeneous baseline risk settings remains poorly defined. We applied meta-analysis-based projection modeling to translate relative risk estimates into absolute, population-level IFI outcomes. Methods: Using pooled odds ratios for IFI associated with systemic corticosteroid exposure from a published meta-analysis (OR 2.84; 95% CI 1.42–5.70), we projected IFI incidence under a proportional odds framework. The primary analysis assumed a baseline IFI incidence of 15% in patients not receiving corticosteroids, with sensitivity analyses conducted across baseline incidences ranging from 10% to 25%. IFI-related mortality was estimated using a case-fatality rate of 45%. Outcomes were expressed as projected IFI incidence, excess IFIs and IFI-attributable deaths per 1,000 patients, population attributable fractions, and one-way sensitivity analyses. Results: At a baseline IFI incidence of 15%, systemic corticosteroid exposure increased projected IFI incidence to approximately 34%, corresponding to an excess of ~190 IFIs per 1,000 patients. This translated into approximately 80 excess IFI-attributable deaths per 1,000 patients, with a plausible range of 25–160 based on uncertainty in the pooled effect estimate. Sensitivity analyses demonstrated a monotonic increase in projected IFI incidence with rising baseline risk, with corticosteroid-associated IFI incidence approaching 50% at higher baseline levels. Population-attributable fraction modeling indicated that when corticosteroid use prevalence exceeded 40%, nearly half of IFIs in the population were attributable to corticosteroid exposure. One-way sensitivity analyses identified the corticosteroid effect size as the dominant driver of excess IFI mortality, exceeding the influence of baseline incidence or IFI case-fatality assumptions. Conclusions: Projection modeling based on meta-analytic risk estimates demonstrates that systemic corticosteroid exposure is associated with a substantial and clinically meaningful absolute increase in IFIs and IFI-related mortality. Translating relative risk estimates into absolute population-level outcomes highlights the potential magnitude of preventable infectious harm associated with corticosteroid use and provides actionable insight to inform risk-mitigation strategies in high-risk hematologic populations.
Integrating multi-cancer early detection into cancer screening programs in the United States: A cost-effectiveness modeling study.
10523 Background: In 2021, standard-of-care (SoC) screening for breast, cervical, colorectal, lung, and prostate cancers in the United States cost $43.2 billion to detect 197,773 cancers, with colonoscopy—used as a primary colorectal screening modality—accounting for $23.7 billion, the largest share of expenditures (54.9%). Multi-cancer early detection (MCED) blood tests could complement SoC single-cancer early detection (SCED) screening but may substantially increase overall costs if implemented without concurrent redesign of screening pathways. Methods: A static decision model used 2021 U.S. SoC screening volumes and costs, 2020 Census data, cancer-specific incidence in high- and low-risk groups, and published SCED and MCED performance to simulate 75.6 million unique screened individuals after adjusting for overlap across programs. We evaluated (1) SoC alone, (2) SoC plus either a low-cost two-step MCED assay (OnceSeek followed by SeekInCare; “OncoSeek Duet”, $143/person) or a higher-priced cfDNA methylation-based MCED test (Galleri, $949/person), and (3) a budget-neutral strategy replacing primary colonoscopy with FIT, designated as SCED 2.0, with savings reinvested to fund OncoSeek Duet for all screened individuals. Results: SoC alone detected 197,773 cancers (262 per 100,000) with a PPV of 0.7% at a total cost of $43.2 billion, or $218,276 per cancer detected. Adding OncoSeek Duet increased detections to 398,586 (527 per 100,000; 2.0-fold), PPV to 43.3% (61.9-fold increase) and total cost to $54.0 billion (25.0% increase), reducing cost per cancer to $135,429, while expanding detection to 9 additional cancer types beyond the 5 SoC targets. Adding Galleri yielded 572,223 cancers (757 per 100,000; PPV of 60.7%) at $114.9 billion total cost (2.7-fold increase) and $200,823 per cancer, improving yield but with markedly higher budget impact than OncoSeek Duet. SCED 2.0 cut costs to $20.0 billion (2.2-fold decrease), reduced cost per cancer to $106,876, saved $23.1 billion, and yielded 187,509 detections (5.2% decrease). Reinvesting these savings to provide OncoSeek Duet for all restored and expanded detection to 391,022 cancers (2.1-fold increase), maintained a high PPV of 42.9%, incurred $78,899 per cancer and produced a $12.3 billion surplus without increasing overall screening expenditure. Conclusions: In this U.S. modeling analysis, integrating MCED into SoC screening substantially increased cancers detected and lowered cost per cancer, particularly when using lower-cost OncoSeek Duet. Optimizing high-cost SCED components, such as colonoscopy, can fully finance population-wide MCED while preserving or improving efficiency, supporting a value-based, budget-neutral path for MCED implementation in national screening programs.
Telehealth use and end-of-life care outcomes among Medicare decedents with cancers.
11012 Background: Telehealth has become an increasingly important care modality following the COVID-19 pandemic. For patients with cancer approaching end of life (EOL), telehealth may be particularly relevant given their substantial symptom burden, need for frequent healthcare services, and declining functional status. Telehealth may facilitate convenient access to care and enhance EOL care quality. However, limited research has examined associations between telehealth use and EOL care among patients with cancer. Methods: We conducted a retrospective, population-based cohort study of EOL telehealth use using 100% Medicare Traditional Medicare (TM) and Medicare Advantage (MA) claims. We included beneficiaries aged 66+ years with cancer who died in 2020-2023 with continuous enrollment in TM or MA during the 12 months preceding death. Patients with cancer were identified by at least 1 inpatient or 2 outpatient claims with relevant diagnosis codes. Telehealth use during the first 6 months of the last year of life was identified using procedure codes and modifiers. We examined validated claims-based EOL care outcomes, including hospice use and place of hospice care, and indicators of potentially burdensome transitions (e.g., late hospice enrollment ≤3 days of death, multiple hospitalizations and emergency department visits ≤30 days of death). Separate multivariable logistic regression models assessed associations between telehealth use and EOL outcomes. Results: Among a total of 2,897,720 Medicare beneficiaries with cancer who died in 2020-2023, mean age was 79.8 years; 44.9% were female, 9.4% were non-Hispanic Black, and 1.7% were Hispanic. Telehealth use in the first 6 months of last year of life was 30.0% in 2020-2023, with utilization peaking in 2021 (47.1%). Among all decedents, 60.7% enrolled in hospice; among hospice users, 73.1% received hospice care at home and 18.6% enrolled ≤3 days of death. In the last 30 days, 11.2% and 13.4% experienced multiple hospitalizations and ER visits respectively. In adjusted analyses, telehealth use was associated with 2.38 percentage points (ppts, 95%CI=2.25 to 2.50) higher likelihood of any hospice use. Among hospice recipients, telehealth use was associated with 5.45 ppts (95%CI=5.31 to 5.60) higher likelihood of home hospice use. Telehealth use was also associated with 2.18 ppts (95%CI=-2.31 to -2.05) lower likelihood of late hospice enrollment. Associations with multiple hospitalizations and ER visits were small and statistically non-significant. Conclusions: Telehealth use among Medicare decedents with cancer was associated with higher hospice use, particularly home hospice, and a lower likelihood of late hospice enrollment, suggesting potential improvements in EOL care transitions. These associations may reflect enhanced care coordination and continuity facilitated by telehealth during the EOL.
Clinical outcomes with low-dose lorlatinib in <i>ALK</i> mutation–positive metastatic lung adenocarcinoma: Experience from a tertiary care center in a developing country.
e20764 Background: Lorlatinib is a highly effective third-generation ALK inhibitor, with a 5-year progression-free survival (PFS) of 60% reported in the CROWN study. However, high cost limits its use in low-resource settings, with fewer than 1% of eligible patients at our center receiving full-dose therapy. Preclinical and early clinical data suggest activity at lower doses. We report real-world outcomes of lorlatinib 25 mg daily administered on a compassionate basis in patients with advanced ALK-rearranged non-small cell lung cancer (NSCLC). Methods: Between August 2024 and April 2025, 35 patients with metastatic ALK-positive NSCLC were treated with lorlatinib 25 mg orally once daily. Median age was 42 years (range, 22–68), 63% were male, and median ECOG performance status was 1 (range, 0–2). Thirty-one percent had a smoking history. ALK rearrangement and fusion variants were assessed using immunohistochemistry and next-generation sequencing. Treatment was continued until progression or unacceptable toxicity. Results: Thirty-two patients (91%) had received at least one prior ALK tyrosine kinase inhibitor. Median follow-up was 10.3 months (95% CI, 9.7–12.8). Overall response rate was 42.9% and disease control rate was 71%. Eighteen patients (51%) had baseline intracranial metastases; prior local therapy included stereotactic radiosurgery in 10% and whole-brain radiotherapy in 77%. Intracranial response and disease control rates were 25% and 37%, respectively. Estimated 1-year overall survival and PFS rates were 68.7% (95% CI, 54.2–87.2) and 66.6% (95% CI, 52.0–85.2). Treatment-related adverse events occurred in 65% of patients, all grade 1–2; hyperlipidemia was most common (57%). Patients experiencing adverse events had higher response rates (45% vs. 14%). No PFS difference was observed between ALK fusion variants 1 and 3. Conclusions: Low-dose lorlatinib demonstrates clinically meaningful systemic and intracranial activity with acceptable toxicity in heavily pretreated ALK-positive metastatic NSCLC in a resource-limited setting. This strategy may offer a pragmatic treatment option when full-dose lorlatinib is not feasible. Demographic and clinical characteristics of patients. Characteristics Count (n=35), in number (%) Age, Mean (SD) 43.23 (10.19) Sex Male 22 (62.9) Female 13 (37.1) Comorbidities Yes 8 (22.9) No 27 (77.1) Hypertension Yes 2 (5.7) No 33 (94.3) Diabetes Mellitus Yes 6 (17.1) No 29 (82.9) COPD No 35 (100) Other Comorbidities Bronchial asthma 2 (5.7) HbCIgG + 1 (2.9) HbSAg + 1 (2.9) Ischemic Herat disease 1 (2.90 No 29 (82.9) TB 4years back 1 (2.9) ECOG PS Baseline 0 1 (2.9) 1 31 (88.6) 2 3 (8.6) Addictions Yes 11 (31.4) No 24 (68.6) Presence of mucin pools Yes 7 (20.0) No 28 (80.0)
A cost-effectiveness analysis of JAK inhibitor therapy versus allogeneic stem cell transplantation in myelofibrosis.
e18606 Background: Optimal management of myelofibrosis (MF) requires balancing the long-term overall survival benefits of allogeneic stem cell transplantation (allo-SCT) against risks associated with allo-SCT including infection, bleeding, graft-versus-host disease (GVHD), and other morbidities. JAK inhibitor therapy offers effective spleen volume reduction and symptom improvement yet lacks overt disease-modifying effect. Given limited evidence to guide this complex decision-making, we assessed the cost-effectiveness of JAK inhibitor therapy versus allo-SCT for 50-year-old patients with higher risk MF who are eligible for transplantation. Methods: We constructed a decision analytic model with a 5-year time horizon. We derived transplant outcomes, chronic GVHD occurrence and duration, non-relapse mortality, JAK inhibitor response and progression, and secondary AML transformation from published clinical trials and large cohort studies. The probability of remaining on chronic GVHD treatment beyond 2 years was modeled as a range to capture the uncertainty in prolonged treatment. Costs (2025$) and utilities used to calculate quality-adjusted life-years (QALYs) were obtained from the literature. We assumed all allo-SCT eligible patients have a matched sibling donor. We evaluated two strategies: upfront allo-SCT versus sequential JAK inhibitor therapy (ruxolitinib -> fedratinib -> momelotinib). Outcomes included life-years, QALYs, total costs, all discounted at 3% annually. Incremental cost-effectiveness ratios (ICERs) were calculated as the difference in total costs divided by the difference in QALYs and compared with a willingness-to-pay (WTP) threshold of $150,000. Results: Upfront allo-SCT incurred a total cost of $681,583 – $733,676 (higher cost corresponding to the upper limit of the probability of remaining on chronic GVHD treatment) and yielded 2.70 – 2.72 QALYs. Upfront JAK inhibitor therapy incurred a total cost of $889,009 and yielded 2.97 QALYs. ICER was $577,807 – 809,880, exceeding the WTP threshold. Results were sensitive to variation in chronic GVHD incidence and duration and JAK inhibitor drug costs. Sensitivity analysis showed that if a novel hypothetical medical therapy reduced the risk of transformation, medical therapy could become cost-effective. Conclusions: Our analysis demonstrates that allo-SCT and JAK inhibitor therapy can provide comparable health outcomes over a 5-years horizon for 50-year-old, transplant-eligible, higher risk MF patients with matched sibling donors. Differences in cost-effectiveness were largely driven by drug cost; at current prices, sequential JAK inhibitor therapy may therefore not be cost-effective. More data are needed to define outcomes after multiple JAK inhibitor failures. Additionally, future therapies that reduce transformation risk could shift the comparative value of medical therapy.
Non-Hodgkin lymphoma and diabetes-related mortality in the United States, 1999-2023: A CDC WONDER analysis.
e19091 Background: Individuals with diabetes mellitus and non-Hodgkin lymphoma (NHL) experience substantially higher morbidity and mortality. This study assessed long-term patterns in diabetes-related mortality among patients with NHL in the United States from 1999 to 2023, stratified by age, sex, race/ethnicity, urban–rural status, and geographic region. Methods: Mortality data for adults aged ≥45 years with NHL and diabetes mellitus from 1999–2023 were obtained from the CDC WONDER database. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated. Joinpoint regression was used to estimate annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals. Analyses were stratified by sex, race/ethnicity, census region, urbanization status, and age group. Results: Between 1999 and 2023, 61,358,342 U.S. adults aged ≥45 years died, including 30,217,781 men (49.24%) and 31,140,551 women (50.75%). Overall AAMRs for diabetes-related mortality among patients with NHL showed a modest, non-significant increase (AAPC 0.78%; 95% CI −0.42 to 1.99; p=0.20). In sex-stratified analyses, males exhibited a significant upward trend (AAPC 1.47%; 95% CI 0.42–2.52; p=0.006), whereas females showed no significant change (AAPC −0.16%; 95% CI −2.18 to 1.89; p=0.87). All census regions demonstrated increasing trends, with the largest rises observed in the South and West. Mortality increases were more pronounced in metropolitan areas, with rates nearly threefold higher than in non-metropolitan areas over the study period. Rising trends were observed across racial and ethnic groups, including Hispanic and non-Hispanic Black populations, with the greatest increases among non-Hispanic White individuals. Conclusions: Diabetes-related mortality among U.S. adults with non-Hodgkin lymphoma has increased over the past decade, despite broader declines in cancer mortality. Disproportionate increases among men, metropolitan residents, and specific racial and ethnic groups highlight important disparities. These findings underscore the need for integrated oncologic and metabolic care strategies and targeted interventions in high-risk populations.
Early corticosteroid dosing after anti-CD19 CAR-T therapy for large B-cell lymphoma: Multicenter associations with neurotoxicity, cytokine release syndrome, and survival.
7020 Background: Corticosteroids are key to CAR-T toxicity management, but the impact of early dosing remains unclear. Over-treatment may blunt efficacy; under-treatment risks severe neurotoxicity. We evaluated early corticosteroid strategies after anti-CD19 CAR-T for large B-cell lymphoma (LBCL). Methods: Multicenter retrospective cohort across 22 U.S. programs (2019–2024). Adults receiving commercial anti-CD19 CAR-T for LBCL were included. Early steroid strategies: (1) Moderate (≤48 h from first fever or grade 1–2 ICANS; 0.5–1 mg/kg for ≤3 days, taper ≤5 days); (2) High-dose (≥1.5 mg/kg or ≥5 days); (3) None within 48 h. Primary endpoint: 12-month overall survival (OS). Secondary endpoints: grade ≥3 ICANS/CRS (Fine-Gray models), ICU admission, hospital stay (LOS), 6-month relapse, and day-30 response. Multivariable Cox/logistic models adjusted for key clinical covariates and center effects. Sensitivity analyses used inverse-probability weighting and time-dependent exposure. Results: N = 2,186; median age 62. Strategies: Moderate 34 %, High-dose 22 %, None 44 %. Versus None, Moderate dosing reduced grade ≥3 ICANS (sub-hazard ratio [sHR] 0.62, 95 % CI 0.50–0.78; p < 0.001) with no OS change (adjusted hazard ratio [aHR] 0.96, 0.84–1.10; p = 0.55). High-dose was linked to worse OS (aHR 1.22, 1.05–1.41) and more early relapse (aHR 1.28, 1.06–1.54) despite similar CRS rates. ICU admission was lower with Moderate vs None (adjusted odds ratio [aOR] 0.78, 0.64–0.95) and LOS shorter (−1.2 days, 95 % CI −2.0 to −0.4). Findings were consistent across age ≥65 and high-risk groups. Conclusions: A moderate, time-limited early steroid approach after anti-CD19 CAR-T reduced severe ICANS without loss of efficacy, whereas high-dose/prolonged use correlated with poorer survival and earlier relapse. Results support adopting standardized moderate early dosing and avoiding routine high-dose regimens. Clinical outcomes by early corticosteroid strategy after anti-CD19 CAR-T. Outcome None (n=963) Moderate (n=742) High-dose (n=481) Adjusted effect vs None (95 % CI) P value 12-mo OS (%) 61 62 55 aHR 0.96 (0.84–1.10); 1.22 (1.05–1.41) 0.55; 0.009 Grade ≥3 ICANS (%) 13.4 8.7 12.9 sHR 0.62 (0.50–0.78); 0.96 (0.75–1.23) <0.001; 0.77 Grade ≥3 CRS (%) 6.1 5.4 5.8 sHR 0.89 (0.67–1.19); 0.94 (0.72–1.23) 0.43; 0.65 ICU admission (%) 18.9 15.4 19.6 aOR 0.78 (0.64–0.95); 1.03 (0.83–1.29) 0.013; 0.77 Hospital LOS (days) 10.1 8.9 10.6 Δ –1.2 (–2.0 to –0.4); Δ +0.3 (–0.5 to +1.1) 0.003; 0.48 Early relapse (6 mo %) 23.7 24.1 29.8 aHR 1.01 (0.87–1.18); 1.28 (1.06–1.54) 0.88; 0.009 Day-30 response (%) 68.2 69.5 66.9 aOR 1.05 (0.90–1.22); 0.94 (0.79–1.12) 0.54; 0.49 Abbreviations: aHR = adjusted hazard ratio; sHR = sub-hazard ratio; aOR = adjusted odds ratio; Δ = adjusted difference in medians.
Patient characteristics and nutrition interventions among referrals to outpatient registered dietitians in a tertiary cancer center: Retrospective analysis.
e13587 Background: Malnutrition in cancer patients is linked to diminished functional capacity, greater treatment toxicity, longer hospital stays, reduced quality of life, and shorter survival. Interventions by Registered Dietitian Nutritionists (RDNs) can improve treatment adherence, QOL, and weight stability. Atrium Health Levine Cancer established the Section of Oncology Nutrition in 2016. Fifteen clinical RDNs and two Wellness RDNs across 23 locations, completing over 16,000 annual encounters. We describe characteristics and nutrition interventions of cancer patients referred to outpatient RDN consult. Methods: Inclusion: age ≥18 years, newly diagnosed, and initial RDN consultation between 2023 and 2024. Referrals were initiated via a Malnutrition Screening Tool (MST) score ≥2 or direct clinician referral. Data from electronic medical records were matched with the Cancer Registry. Descriptive statistics summarize patient characteristics and nutrition interventions. Results: 2,243 consultations were matched with the Cancer Registry. Median age was 65, 47% were female, 70% White, 25% Black, and 5% Latino. Most were married (55%) and on Medicare (50%). Eight percent were underweight, 38% normal weight, and 54% overweight or obese. Gastrointestinal (27%), head and neck (18%), lung (14%) cancers were most common. Fifty-seven percent had stage III-IV disease. Twenty-six percent received RDN consultation within 30 days of diagnosis. Fifty-three percent had an MST score of ≥2. Following RDN consultation, 92% had a nutrition-related diagnosis including: inadequate oral intake (27%), unintended weight loss (17%), and predicted inadequate energy intake (14%). Most frequent interventions included nutrition education (63%), medical supplements (54%), and diet modification (26%). Conclusions: Comprehensive RDN evaluations revealed significant nutrition-related needs, highlighting the importance of early and proactive nutrition care in cancer. Most patients were referred to RDN ≥30 days after diagnosis underscoring barriers to early referrals. The MST underestimated the prevalence of nutrition-related problems, and most patients were overweight or obese.
Geographic and rural–urban patterns in pediatric and AYA malignant brain tumor mortality in the United States: A CDC WONDER analysis.
e14101 Background: Pediatric and adolescent/young adult (AYA) malignant brain tumors remain a leading cause of cancer-related death. Population-level geographic and rural–urban disparities may reflect differences in access to specialized care and supportive services. Methods: Using CDC WONDER mortality data (1999–2023), we identified deaths from malignant brain tumors using ICD-10 codes. Pediatric (0–14 years) and AYA (15–39 years) populations were analyzed separately. Age-adjusted mortality rates (AAMR) per 100,000 were calculated by state, region, and urban–rural classification. Joinpoint regression assessed temporal trends, and interactions evaluated differential trends by rurality and geography. Results: A total of 14,532 deaths were analyzed. National AAMR declined modestly in pediatric patients (AAPC −1.1%, p < 0.01) but remained relatively stable in AYA patients (AAPC −0.3%, p = 0.12). Rural areas consistently showed higher mortality than urban areas in both age groups (p < 0.01). Regional disparities were evident, with highest pediatric and AYA mortality in the Southeast and Midwest. Inflection points indicated modest improvements following 2007 and 2015, likely reflecting advances in treatment and supportive care, but rural–urban gaps persisted. Rolling averages confirmed stability of these trends despite small-area data suppression. Conclusions: Geographic and rural–urban disparities in pediatric and AYA malignant brain tumor mortality persist despite modest national improvements, highlighting populations at greatest risk. Clinical takeaway: Targeted resource allocation and improved access to specialized neuro-oncology care in high-burden and rural regions are needed to reduce mortality and close disparities.
Trends and disparities in mortality from malignant neoplasms of digestive system and renal failure in the United States, 1999-2023.
11135 Background: Malignancies of the digestive system represent a substantial global health burden, often exacerbated by coexisting renal failure, which complicates therapeutic interventions and significantly elevates mortality risk. This study aims to analyze and interpret annual mortality trends and disparities among adults in the United States from 1999 to 2023, for various demographic and geographic factors. Methods: The mortality data from the CDC WONDER multiple cause of death files for adults aged ≥25 years were used to analyze age-adjusted and crude mortality rates (AAMRs and CMRs) per 1,000,000 through ICD 10 code: C15-C26 (digestive system malignant neoplasms) and ICD 10 code: N17-N19 (renal failure), stratified by year, gender, race/ethnicity, place of death and geography. Joinpoint regression was used to estimate average annual percent change (AAPC) and annual percent change (APC) with 95% confidence intervals (CIs). Statistical significance was defined as p < 0.05. Results: From 1999 to 2023, a total of 164,004 deaths were reported due to malignant neoplasms of the digestive system and renal failure, mostly occurring in medical facility inpatient settings. The overall AAMR increased from 27.58 in 1999 to 36.84 in 2023 (AAPC: 1.17; 95% CI: -0.01 to 2.36; p = 0.05), with an initial decline observed between 2011 and 2017 (APC: -4.91; p < 0.001), followed by a notable increase through 2023 (APC: 8.26; p < 0.001). Men are noted to have higher AAMR than women (42.40 vs 19.19). Adults aged 65 and above experienced the highest CMR (110.96), whereas adults aged 45–64 years exhibited the greatest annual increase (3.19%; p < 0.001). By race, the highest AAMR was among non-Hispanic (NH) Black individuals (53.41), and the lowest was among NH White individuals (25.73). Geographic disparities were evident, with the West region having the highest AAMR (31.80) and the Northeast region having the lowest AAMR (27.77). Non-metropolitan areas showed higher AAMR than metropolitan areas (29.42 vs 27.91). At the state level, the District of Columbia and South Dakota ranked highest, placed in the top 90th percentile during 1999–2020 and 2021–2023, respectively. Conclusions: Mortality related to malignant neoplasms of the digestive system and renal failure has increased over the past two decades, with disproportionate burden among older adults, men, NH Black individuals, those living in non-metropolitan areas, and the West region, underscoring the need for targeted prevention, early detection, and equitable, integrated care. Average annual percent change (AAPC) of neoplasms of digestive system and renal failure related age-adjusted mortality rates in the United States, 1999 to 2023. Variable Deaths AAPC (95%CI) Overall 164,004 1.17 (-0.01 to 2.36)
Efficacy of high-dose chemotherapy in adult patients with relapsed or refractory medulloblastoma.
2087 Background: Adult medulloblastoma (MB) is rare, and there is no standard salvage approach for relapsed or refractory cases. High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has shown potential, but evidence in adults remains limited. This study evaluated the response rate, survival and toxicity after HDC with ICE regimen followed by ASCT in MB, with further focusing on post-ASCT response and pretransplant intracranial residual disease (ICRD). Methods: We retrospectively analyzed adult patients with relapsed/refractory MB who underwent HDC with the ICE regimen followed by ASCT. Baseline features, treatment response, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity were evaluated. Subgroup analyses focused on post-ASCT response and pretransplant intracranial residual disease (ICRD). Results: The study included 23 patients (median age: 24 years; male: 52%, with 43% classic subtype and 61% pretransplant ICRD). The overall and complete response (CR) rates to HDC was 73.9% and 48%, respectively. The median PFS was 12.8 months, and OS was 45.1 months, with 2-year PFS and OS rates of 31% and 63%, respectively. Patients achieving CR after ASCT had significantly longer OS (NR vs 16.4 months; HR, 0.15; 95% CI, 0.03–0.72; P=.02), corresponding to an 85% reduction in mortality risk compared with non-CR patients. OS was markedly shorter in patients with pretransplant intracranial residual disease compared with those without (22.5 vs. 74.0 months; HR, 7.08; 95% CI, 1.3–36.3; p = 0.008).The large cell/anaplastic subtype remained the poorest prognostic group despite ICE induction. Toxicity was dominated by universal grade 4 myelosuppression and febrile neutropenia, but no transplantation-related mortality occurred. Conclusions: This study showed that HDC with ICE followed by ASCT is feasible in adults with relapsed/refractory MB, with encouraging survival and manageable toxicity. Pretransplant ICRD clearance and achievement of CR were major prognostic determinants, while non-CR patients remained at high risk, highlighting the need for treatment intensification in this subgroup.
Machine learning–integrated transcriptomic clustering for prognostic stratification in epithelioid pleural mesothelioma.
8051 Background: Survival outcomes in pleural mesothelioma (PM), particularly within epithelioid PM (ePM), are heterogeneous and inadequately captured by histological classification. We applied machine learning (ML) methods integrating transcriptomic and clinical features to improve prognostic stratification in ePM. Methods: RNA sequencing was performed on FFPE tumor samples from 125 ePM patients treated at two Italian centers (2006-2021). Overall survival (OS) was categorized as long (> 36 months), intermediate (12-36 months), or short (≤12 months). Unsupervised clustering of highly variable genes identified transcriptomic subgroups, and GSEA was performed. A previously published 20-gene sarcomatoid-like transcriptional score (S-score), derived from single-cell data was calculated. ML models were developed using age, sex, S-score, and a cluster-derived score related to cell proliferation as input features. Logistic Regression (LR) and Random Forest (RF) classifiers were trained to predict long and short survival, using class-balanced weighting and 5-fold stratified cross-validation. Model performance was assessed using AUC-ROC and balanced accuracy. Model interpretability was evaluated with SHapley Additive exPlanations (SHAP). External evaluation was performed in the TCGA PM cohort with cohort-specific standardization. Results: Unsupervised transcriptomic analysis identified three clusters with distinct survival patterns. Cluster 1 was enriched for immune-related pathways and associated with longer survival; Cluster 2 exhibited proliferative and cell-cycle-related programs and was enriched in short-survival patients. Cluster 3 showed immune-related transcripts, with variable expression patterns across histology and survival groups. Given the convergent GSEA results, Cluster 2 was selected as a ML feature. Both the S-score and Cluster 2 score were associated with OS, with stronger survival discrimination for Cluster 2. ML models showed good discriminative performance for long survival prediction (cross-validation AUC-ROC: LR 0.83 ± 0.10; RF 0.83 ± 0.04), with similar results in the TCGA cohort (LR AUC-ROC = 0.84; RF = 0.77). Predictive performance for short survival was moderate. SHAP analysis identified Cluster 2 score as the main contributor to ML predictions, with higher values associated with increased risk of short survival. Conclusions: Machine learning models integrating transcriptomic clustering with clinical variables improve prognostic stratification in ePM. ML-based risk prediction builds upon transcriptomic features, capturing survival-relevant heterogeneity beyond histology. These findings support the use of ML as a complementary tool to transcriptomic profiling for prognostic assessment in ePM.
Cell-free DNA methylation profile–based fusion epigenotyping to enhance <i>ALK</i> fusion detection in NSCLC patients.
3070 Background: Short read lengths in next-generation sequencing and targeted panel probe design pose challenges to fusion detection by impairing the resolution of complex genomic rearrangements and the accurate mapping of intronic breakpoints. To address these limitations, we developed a cell-free DNA (cfDNA) methylation-based fusion epigenotyping method that leverages fusion-associated tumor epigenetic signatures to complement genomic-based methods and increase the fusion detection sensitivity of our liquid biopsy. We validated EML4 - ALK fusion detection by this algorithm in non-small cell lung cancer (NSCLC) using paired clinical tumor tissue and cfDNA samples. Methods: We trained a binary classifier to discriminate EML4-ALK fusion-positive from fusion-negative NSCLC using cfDNA methylation signal and genomic molecule support. To validate the epigenotyping classifier, an independent cohort of 577 clinical NSCLC samples was selected with paired tumor tissue and Guardant360 Liquid (Guardant Health, Palo Alto, CA) cfDNA for each patient (with epigenomic tumor fraction > 0.03%). The cohort included 94 tissue-confirmed fusion-positive samples (78 cfDNA genomic positives and 16 cfDNA genomic false negatives) with EML4-ALK detected in tumor tissue, and 483 tissue-confirmed fusion-negative samples ( ALK fusion negative in both tissue and paired cfDNA). The epigenotyping classifier predictions in cfDNA were evaluated against tissue-based orthogonal truth. Results: Among tissue-confirmed fusion-positive samples, tissue-liquid assessment showed a high positive percent agreement (PPA) / sensitivity of 89.36% (84/94), as well as 100% concordance with genomic caller positives (78/78). The rate of rescued fusions by the epigenotyping classifier from genomic false negative liquid cases was 38% (6/16). Among tissue-confirmed fusion-negative samples, tissue-liquid assessment showed a high negative percent agreement (NPA) / specificity of 99.38% (480/483). The false positive rate (FPR) of high confidence calls (probability exceeding a 99.7% specificity threshold or with partial genomic evidence) was 0.0% (0/483). Conclusions: cfDNA methylation-based fusion epigenotyping substantially increased detection of actionable ALK fusions while maintaining high specificity, as demonstrated by tissue-liquid concordance. The results of this approach showed the clinical value of giving NSCLC patients an increased likelihood to receive more effective, less toxic ALK inhibitor therapy, while the minimized FPR helps ensure appropriately matched treatment decisions.
The glucocorticoid toxicity index: Assessing corticosteroid toxicity in patients with immune-related adverse events from cancer immunotherapy for solid tumors.
e24194 Background: Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) requiring systemic corticosteroids. The toxicity of glucocorticoids has not been studied in immuno-oncology, despite being the mainstay of irAE management. We applied the Glucocorticoid Toxicity Index (GTI), a validated, multidimensional tool developed to assess the duration and severity of steroid toxicity in rheumatology, as a comprehensive metric to evaluate the toxicity of corticosteroids at baseline and over time for irAEs. Methods: This exploratory secondary data use analysis utilized data from a set of Roche/Genentech trials with atezolizumab across multiple tumor types. Patients included were: corticosteroid-naive, had an irAE event within 7 days of initiating ICIs, and were treated with corticosteroids (IV/oral). Data was stored in a Snowflake based relational database to facilitate analysis using a mixture of SQL queries and Python code. The GTI score was computed according to methods detailed by Miloslavsky et al., 2017, where available. e.g. (BMI, BP, glucose levels, were directly included; while myopathy, infection, significant organ impairment, included as reported by the treating investigator.). Results: Our analysis included 558 atezolizumab treated patients across 32 clinical trials (primarily NSCLC 21.7%, melanoma 19.2%, and breast cancer 12.9%). Baseline GTI scores varied across patients (range: -18 to 262). GTI score varied with corticosteroid use, with corticosteroid initiation for irAEs resulting in a 236% increase in average GTI score (8.6 to 28.9) by day 168. Conversely, patients with low GTI scores (0 or lower) declined from 67% at corticosteroid initiation to 28% at day 168 post corticosteroid use. Patients with low baseline GTI scores ( < = 10) reduced from 77.96% to 48.75% at day 168. Further analysis is ongoing to identify baseline features (age, gender, ICI mono vs combination) that associate with GTI score, and the association between GTI and clinical outcomes (PFS and OS). Conclusions: In this analysis, we identify that the GTI score is assessable at baseline and longitudinally in ICI-treated patients, and correctly identifies the effects of corticosteroids for irAEs, in 558 ICI-treated patients. Thus, the GTI represents a potential novel baseline and longitudinal biomarker of corticosteroid toxicity for management of ICI-induced irAEs. This approach may be leveraged to implement risk stratification criteria to inform corticosteroid duration for irAEs, and assist clinicians in timing of second-line immunosuppression in those with high GTI scores +/- unacceptable toxicity risk from corticosteroids.
Primary squamous cell carcinoma of the pancreas: A SEER-based analysis.
e16389 Background: Primary squamous cell carcinoma of the pancreas (PSCCP) is an exceedingly rare malignancy with a poor prognosis. Given the limited literature on PPSCC, we conducted a population-based analysis to identify patient demographics, treatment patterns, and predictors of survival. Methods: Patients with histologically confirmed PSCCP diagnosed between 2000 and 2020 were identified from the SEER database. Demographics, socioeconomic factors, tumor stage, and initial treatment modality were extracted. Overall survival (OS) was estimated by the Kaplan-Meier method. Associations with all-cause mortality were assessed using univariable and multivariable Cox proportional hazards models, adjusting for key demographic, clinical, and treatment covariates. Patients with unknown stage were excluded from the multivariate model. Statistical analyses were performed using R version 4.5.2. Results: Among 397 identified PSCCP cases, the cohort was 51.6% male, 59.7% were non-Hispanic White, 15.9% Black, and 11.6% Hispanic, with 90.4% residing in metropolitan areas. Disease characteristics showed that 49.9% of cases had distant metastasis, 26.7% had regional metastasis, and 5.5% had localized spread. Regarding treatment, 45.3% of cases received chemotherapy, 14.1% underwent surgery, and 9.8% received radiation. Median OS was 3.0 months (IQR 1.0-9.0) with an estimated one-year OS of approximately 20%. Univariable analysis showed significantly increased mortality with older age (HR = 1.55, 95%CI 1.26-1.91) and distant stage (HR = 2.64, 95% CI 1.59 to 4.36), while surgery (HR = 0.21, 95%CI 0.14-0.29) and chemotherapy (HR = 0.64, 95%CI 0.52-0.78) were associated with improved survival (all p < 0.001). Notably, median OS in those who underwent surgery was 18 months, compared to 3 months in those who did not (log-rank p < 0.001). On multivariate analysis, age ≥65 years (HR = 1.37, 95% CI 1.08-1.75, p = 0.011) and distant stage (HR = 1.83, 95% CI 1.07-3.14, p = 0.028) remained independently associated with worse survival. However, surgery (adjusted HR = 0.20, 95% CI 0.13-0.31, p < 0.001) and chemotherapy (HR = 0.44, 95% CI 0.34-0.56, p < 0.001) were independently associated with improved survival. Conclusions: PSCCP is a rare malignancy with a median OS of 3 months, frequently presenting with distant-stage disease. Advanced stage remained an independent predictor of mortality, while surgical resection was associated with a substantial survival benefit. No significant disparities in survival were observed by sex, race, or socioeconomic status. Results may be limited by the timing of diagnosis, the surgical candidacy of patients, or the small sample size. These findings emphasize the importance of early detection and multimodal therapy when feasible.