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Cost-effectiveness analysis in the era of systemic immunotherapy for BCG-naive high-risk non–muscle-invasive bladder cancer in the United States, the United Kingdom, and China.
4598 Background: Non–muscle-invasive bladder cancer (NMIBC) has entered the era of systemic immunotherapy, with randomized trials evaluating the addition of systemic immunotherapy to BCG to improve disease control. The cost-effectiveness of combining immune checkpoint inhibitor (ICI) with BCG in BCG-naive high-risk NMIBC (HR-NMIBC) remains unclear. We therefore conducted a multinational cost-effectiveness analysis in the United States, United Kingdom, and China based on the CREST and POTOMAC studies. Methods: We developed a Markov model to evaluate treatment strategies for patients with BCG-naive HR-NMIBC over a 5-year time horizon from healthcare payer perspectives, with health outcomes measured in quality-adjusted life-years (QALYs). Total costs, QALYs, and incremental cost-effectiveness ratios (ICERs) were calculated for each strategy. Model robustness was assessed using deterministic and probabilistic sensitivity analyses. Results: Health outcomes were comparable across strategies, with BCG, durvalumab plus BCG, and sasanlimab plus BCG yielding 4.11, 4.31, and 4.18 QALYs, respectively. In the US, durvalumab plus BCG increased costs by $159,021 compared with BCG, resulting in an ICER of $827,706 per QALY, exceeding the willingness-to-pay (WTP) threshold of $150,000 per QALY. In the UK, the corresponding ICER was £503,944 per QALY, far above the WTP threshold of £20,000 per QALY. In China, the ICER reached ¥3,860,692 per QALY, exceeding the threshold defined as three times the national per-capita GDP (¥257,145). Sasanlimab plus BCG was strictly dominated by durvalumab plus BCG in all settings. Consequently, neither systemic immunotherapy–based strategy was cost-effective under the evaluated WTP thresholds. BCG was optimal in all probabilistic simulations, and ICI prices were the primary drivers of cost-effectiveness for systemic immunotherapy–based strategies. Conclusions: Despite modest clinical benefits, the high cost of systemic immunotherapy plus BCG precludes cost-effectiveness across health care systems, with BCG alone remaining the preferred strategy under current pricing. Future efforts should focus on drug price reductions and precision patient selection to improve the value proposition of early systemic immunotherapy. Costs ($; US) Costs (£; UK) Costs (¥; China) Incremental costs ($; US) Incremental costs (£; UK) Incremental costs (¥; China) Effectiveness (QALYs) ICER ($/QALY; US) ICER (£/QALY; UK) ICER (¥/QALY; China) BCG 48,828 21,307 119,383 - - - 4.11 - - - Durvalumab + BCG 207,849 118,126 861,110 159,021 96,819 741,728 4.31 827,706 503,944 3,860,692 Sasanlimab + BCG* 309,654 138,329 932,331 260,826 117,023 812,948 4.18 3,726,091 1,671,751 1,1613,542 *The Sasanlimab plus BCG strategy is strictly dominated by the Durvalumab plus BCG strategy (higher cost and lower effectiveness).
Efficacy of angiotensin receptor–neprilysin inhibitor (ARNI) for prevention of cancer therapy–related cardiac dysfunction: A meta-analysis of randomized controlled trials.
e24182 Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a clinically significant complication of anticancer treatments, including anthracyclines and trastuzumab, often necessitating dose reduction or discontinuation of potentially life-saving therapy. While angiotensin receptor-neprilysin inhibitors (ARNI) have demonstrated mortality and hospitalization benefits in heart failure with reduced ejection fraction, their efficacy in preventing chemotherapy-induced cardiotoxicity remains controversial due to conflicting results and a lack of large-scale data. Therefore, we performed a meta-analysis to evaluate the efficacy of ARNI for the prevention of cardiotoxicity in patients receiving chemotherapy. Methods: We searched PubMed, Embase, and Cochrane Central from intercept till 17 December 2025 for studies evaluating the benefit of ARNI in preventing CTRCD among patients undergoing cardiotoxic cancer therapy. The primary outcomes assessed were changes in left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), N-terminal pro-brain natriuretic peptide (NT-proBNP), and troponin T. Statistical analysis was performed using Review Manager, and heterogeneity was assessed using the I2 statistic. The study protocol was registered with PROSPERO (CRD420251266270). Results: A total of 442 patients from four RCTs were included, with follow-up periods ranging from 6 to 18 months. The analysis of changes in LVEF showed a trend toward improvement (mean difference 1.18; 95% CI -0.04 to 2.40; p = 0.06), though this did not reach statistical significance. There were no statistically significant differences observed in changes in GLS (mean difference -0.94; 95% CI -2.43 to 0.55; p = 0.14), NT-proBNP (mean difference -0.94; 95% CI -9.57 to 7.70; p = 0.69), or troponin T (mean difference 0.06; 95% CI -1.13 to 1.26; p = 0.92). Conclusions: In conclusion, prophylactic treatment with ARNI in patients undergoing cardiotoxic cancer therapy did not result in statistically significant changes in LVEF, GLS, or cardiac biomarkers (NT-proBNP and troponin T), although a non-significant trend toward preserved LVEF was observed. The lack of statistical significance may be attributable to limited statistical power due to small sample sizes and heterogeneity across cancer therapies. Given the observed trend in LVEF preservation, further adequately powered, large-scale RCTs focusing on specific chemotherapy regimens are needed.
Emergency presentation and inpatient vulnerability in sinonasal malignancies: National evidence of a diagnostic delay phenotype.
e23248 Background: Sinonasal malignancies are rare, heterogeneous tumors characterized by nonspecific early symptoms and frequent diagnostic delay, leading to advanced disease at presentation. While outpatient management and multimodal therapy have been extensively reviewed, national inpatient presentation patterns and rescue outcomes remain poorly defined. Methods: A survey-weighted analysis of the National Inpatient Sample from 2016–2023 was performed, identifying adult hospitalizations with sinonasal malignancies (C30–C31) in any diagnosis position and excluding admissions with palliative care coding. A diagnostic delay phenotype was defined by nonelective admission accompanied by acute organ failure at presentation, including sepsis, shock, respiratory failure, or acute kidney injury. Outcomes included in-hospital mortality, ICU escalation, failure-to-rescue (death following a major complication), length of stay, hospitalization cost, and discharge disposition. Outcomes were contextualized through comparisons with other rare cancers and common malignancies. Results: Sinonasal malignancies accounted for 0.66% (95% CI, 0.64%–0.69%) of cancer hospitalizations and were predominantly nonelective at 57.16% (95% CI, 55.63%–58.69%). Acute organ failure at presentation occurred in 21.53% (95% CI, 20.34%–22.72%) of sinonasal admissions, with sepsis in 7.70% (95% CI, 6.93%–8.46%) and respiratory failure in 8.77% (95% CI, 7.98%–9.56%). Overall in-hospital mortality was 1.64% (95% CI, 1.33%–2.02%). Among admissions with major complications, failure-to-rescue mortality was 4.23% (95% CI, 3.39%–5.27%). ICU escalation occurred in 4.93% (95% CI, 4.33%–5.52%), with post-ICU mortality of 27.74% (95% CI, 26.25%–29.27%). Compared with common cancers, sinonasal malignancies demonstrated higher rates of nonelective admission and acute organ failure but similar overall mortality, indicating preserved rescue despite high-acuity presentation. Conclusions: Sinonasal malignancies exhibit a distinct inpatient diagnostic delay phenotype marked by emergency presentation and acute organ failure at admission. Despite high physiologic acuity, inpatient mortality and failure-to-rescue are not disproportionately worse, suggesting that delayed recognition primarily shifts how patients present rather than whether they survive hospitalization. These findings complement existing clinical literature by identifying inpatient presentation and rescue as critical, understudied dimensions of sinonasal cancer care.
Association of baseline quality of life (QOL) and early death in patients with metastatic renal cell carcinoma (mRCC) in the real-world prospective observational ODYSSEY study.
4559 Background: Baseline QOL has been linked to survival in mRCC therapy clinical trials (Cella, 2024); however, there is a paucity of prospectively collected real-world QOL data across front-line management strategies. We used data from ODYSSEY to examine the relationship between baseline QOL and early death. Methods: ODYSSEY is a multi-site, prospective observational study of 468 US pts with mRCC. Pts must have mRCC (any histology); have no prior systemic therapy (ST) or be within 3 months of starting ST; and follow up at a PCORnet study site. Exclusion criteria include treatment for cancer except mRCC. The primary objective is to determine patterns of change in QOL and symptom burden of pts with mRCC. Early death was defined as death within 12 months post-enrollment. All pts with non-missing FKSI-19 or FKSI-DRS at enrollment were included. Cumulative event probabilities as a function of time were stratified by either < or ≥ median QoL value and plotted as a step function vs time since enrollment to create cumulative event curves. To determine association between QoL at enrollment and early death, separate Cox proportional hazards models (unadjusted and adjusted) for time-to-first-event as a function of baseline QoL were fit. The adjusted model controlled for the following baseline covariates: IMDC risk (favorable vs intermediate or poor), histology (clear cell vs non). Results: As of 1/5/26, 468 pts were enrolled; 425 had non-missing FKSI-19 or FKSI-DRS at enrollment (329 immediate ST, 96 deferred ST [DST]). ST included 129 IO-IO, 108 IO-TKI, 92 Other. DST included 57 Active Surveillance, 22 Local Therapy Planned, 17 Other/Missing. 209 and 190 pts have < median FKSI-19 (score = 59) and FKSI-DRS (score = 29), respectively; 216 and 235 pts have ≥ median FKSI-19 and FKSI-DRS, respectively. Those below the median have lower rates of nephrectomy, worse IMDC risk and KPS, shorter time since RCC diagnosis, and higher rates of bone metastasis (all p<0.05). Cumulative event probabilities for death at 12 months are 21% and 7% in those < and ≥ median baseline FKSI-19, respectively; and 21% and 7% in those < and ≥ median baseline FKSI-DRS, respectively. For FKSI-19, the unadjusted hazard ratio (HR) for early death is 0.55 (95% CI: 0.43 – 0.70; p<0.001) and adjusted HR is 0.65 (0.49 – 0.85; p = 0.002) per 1 SD higher score. For FKSI-DRS, the unadjusted HR for early death is 0.57 (95% CI: 0.46 – 0.71; p<0.001) and adjusted HR is 0.66 (0.51 – 0.86; p =0.002) per 1 SD higher score (higher score indicates better QOL). Conclusions: Across management strategies in our ODYSSEY cohort of systemic therapy naïve mRCC patients, better baseline QOL was associated with better survival. This is to our knowledge the largest reported real world mRCC cohort with prospectively collected PROs. Future analyses will focus on association of outcomes with longitudinal PROs. Clinical trial information: NCT04919122 .
Differences in outcomes for elderly patients with DLBCL treated at academic vs community programs: A 10-year survival analysis.
7066 Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell malignancy that primarily affects older adults. Optimal treatment management in the geriatric population is challenging due to the high-risk disease biology and their age-specific vulnerabilities. Combination chemotherapy is effective, however, due to frailty often a dose-reduced regimen is administered. This large population real-world study compares demographic, clinical and survival characteristics of patients older than 75 years and compares Academic Cancer Programs (ACP) vs Community Cancer Programs (CCP). Methods: A retrospective analysis using the National Cancer Database was conducted on 103,671 patients (ACP: 51,848; CCP: 51,823) diagnosed with DLBCL between 2004 and 2022 was carried out. ACP included academic and National Cancer Institute-designated research centers; CCP included community, comprehensive community, and integrated network cancer programs. Kaplan-Meier and Cox regression models were used to compare overall survival (OS), adjusting for: age, race/ethnicity, insurance status, Charlson-Deyo comorbidity score, and distance from treating facility. Results: Patients in ACP and CCP were mostly females with a median age of 81 years. For both cohorts the majority were non-Hispanics and Whites; however, for ACP it was noted a higher rate of Hispanics (6% vs 5%) and Blacks (5% vs 3%) compared to CCP. Most of the patients in both groups were from the Metropolitan area, but the median distance in miles for ACP was 9.0 vs 7.4 in CCP. Treatment rates were higher for ACP vs community settings (63% vs 59%, p<0.001), with more patients presenting at Stage IV (36% vs 33%, p<0.001). Better OS was noted in elderly patients treated at ACP, p<0.001. The median OS for ACP was of 1.79 years vs 1.50 years at CCP, which was consistent with a longer median follow up time of 17.7 months vs 14.1, p<0.001. This survival advantage remained consistent throughout long-term observation, with 2-year OS rates of 49% at ACP [CI: 0.48,0.49] vs 46% at CCP [CI: 0.459,0.468], 5-year OS of 34% [CI: 0.336,0.346] vs 32% [CI: 0.317,0.327], and 10-year OS of 16% [CI: 0.154,0.164] vs 15% [CI: 0.142,0.151], respectively. Conclusions: Among patients aged ≥75 years with DLBCL, OS differed by treatment facility type, with a statistically significant but modest survival advantage observed among patients treated at ACP compared with CCP (log-rank p<0.001). This difference occurred in the context of higher treatment rates and greater disease severity at presentation. Given the relatively small absolute survival differences, these findings suggest that care for older adults with DLBCL is largely standardized across practice settings; however, this highlights an opportunity to optimize treatment delivery and intensity, supportive care, and geriatric-focused management in both academic and community programs.
Impact of synbindin deficiency on immune checkpoint blocker–induced systemic inflammation and multi-organ damage.
12139 Background: Immune-related adverse events (irAEs) are a major safety limitation for the broad application of immune checkpoint blockade (ICB) in oncology, yet their precise molecular mechanisms remain unclear. Synbindin, a tethering-associated protein involved in vesicular trafficking and related processes, plays a key role in immune-cell activation and activation of inflammatory signaling pathways and therefore may represent an important initiator and predictive factor for irAEs. Methods: We generated constitutive whole-body Trappc4 knockout (Trappc4-KO) C57BL/6 mice and administered either anti-PD-1 monotherapy or combined anti-PD-1 plus anti-CTLA-4 immune checkpoint blockade via intraperitoneal injection. Plasma biochemical indices and the extent of organ injury were assessed following treatment. Results: Trappc4-KO mice receiving combined anti-PD-1/anti-CTLA-4 treatment exhibited markedly more severe immune-related toxicity and multi-organ injury than wild-type controls. Biochemically, markers of hepatic injury (AST, ALT) were substantially elevated, indicating liver dysfunction; renal function markers (serum creatinine and blood urea nitrogen) were significantly increased, consistent with kidney injury; and cardiac markers (CK-MB, cTnT, cTnI) were also markedly raised. A similar trend, although less pronounced, was observed following anti-PD-1 monotherapy. Histopathological examination corroborated these findings: H&E sections of affected organs showed prominent focal immune cell infiltration, cellular swelling, and areas of necrosis. Conclusions: These data demonstrate that Trappc4 deficiency significantly exacerbates ICB-induced systemic inflammation and multi-organ damage, suggesting that Synbindin plays a critical protective role in the development of irAEs.
Reduction in circulating tumor DNA (ctDNA) in relation to radiographic response and tumor PD-L1 expression in a phase 1 study of PDL1V (PF-08046054) in patients with non-small cell lung cancer (NSCLC).
8609 Background: PDL1V (PF-08046054) is a novel, first-in-class, PD-L1–directed vedotin antibody-drug conjugate that consists of MMAE connected to an anti–PD-L1 antibody. Prior results from the phase 1 study (NCT05208762) showed promising antitumor activity and manageable safety in patients (pts) with refractory (2L+) NSCLC. We present ctDNA results from an exploratory analysis in this study. Methods: C5851001 is a phase 1 study in advanced solid tumors. Pts with NSCLC must have prior exposure to platinum and anti–PD-(L)1 agents, targeted therapies for tumors expressing AGAs, and measurable disease per RECIST 1.1. PD-L1 expression status by tumor proportion score (TPS) was reported by local sites. Paired baseline (T0) and on-treatment (T1; C2D15 to C3D1) ctDNA samples were used for ctDNA analyses using a methylation-based tissue-free assay (Guardant Infinity). Tumor fraction (TF) was quantified by methylation score. Changes in ctDNA from T0 to T1 were compared between subgroups using the Wilcoxon test. Results: As of Nov 22, 2025, 55 pts with 2L+ NSCLC received PDL1V: median age 63 yrs, 70.9% ECOG PS 1, 29.1% squamous (SQ) histology, 67.3% TPS ≥1%. The median number of prior lines of therapy was 2.0 (range, 1-8). The investigator-assessed confirmed objective response rate (ORR) was 32.4% (95% CI, 18.0-49.8) in pts with TPS ≥1% NSCLC (n=37) and 0% in TPS <1% (n=18). Grade 3-4 TRAEs occurred in 32.6%. Paired T0 and T1 samples were available in 47/55 pts. ctDNA analysis showed 46/47 pts (98%) had detectable ctDNA at baseline. At T1, ctDNA TF decreased in 36/46 pts (78%) and became nondetectable in 7/46 (15%). Pts with complete or partial responses (CR/PR) had a greater median ctDNA reduction from T0 to T1 than nonresponders (−99% vs −37%, p<0.001). Pts with TPS ≥1% NSCLC had a greater median ctDNA reduction than pts with TPS <1% NSCLC (−77% vs −4%, P =0.0023). For pts with TPS ≥1% NSCLC, there was no significant difference in median ctDNA reduction between nonsquamous (NSQ) and SQ histology (–73% vs –87%, p=0.48). Conclusions: PDL1V monotherapy showed promising antitumor activity with a manageable safety profile in pts with 2L+ TPS ≥1% NSCLC. Most pts had ctDNA reduction with PDL1V treatment, with greater ctDNA reduction in pts with radiographic response and TPS ≥1% NSCLC. These data further support evaluation of PDL1V in the ongoing phase 3 trial in 2L+ PD-L1+ NSCLC, SQ and NSQ (NCT07144280/PADL1NK-005) and the continued use of ctDNA for response monitoring and potential early prediction of clinical benefit. Clinical trial information: NCT05208762 . Subgroup n ctDNA reduction (%) from T0 to T1median (lower/upper quartile) By ORR CR/PR 12 −99 [−100 to −93] SD/PD 34 −37 [−72 to 5] By PD-L1 status TPS <1% 14 −4 [−36 to 26] TPS ≥1% 32 −77 [−98 to −39] TPS 1%-49% 17 −72 [−82 to −38] TPS ≥50% 15 −91 [−100 to −41] By histology TPS ≥1% NSQ 24 -73 [-95 to -38] SQ 8 -87 [-98 to -70]
Genomic determinants of survival after biliary tract cancer resection.
e16301 Background: Surgical resection is the mainstay for localized, resectable biliary tract cancers (BTCs). Although genomic clusters have been associated with outcomes in BTCs, data linking specific molecular subtypes to post-surgical outcomes remain limited. We aimed to evaluate the prognostic role of tumor genetic signatures in patients with BTC undergoing curative-intent surgery. Methods: We retrospectively analyzed Liver Multi-Disciplinary Clinic (LMDC) patients who underwent curative-intent surgery between 2015 and 2025 with pathology proven BTC. We included patients with detailed pathological records and next generation sequencing (NGS) results. Our endpoints of disease-free survival (DFS) and overall survival (OS) were defined as the time from surgery to their first documented disease recurrence and death from any cause, respectively. Results: There were 97 patients (52.6% male, 47.4% female) in our cohort with a mean age of 65.1 years. Most patients had AJCC Stage II (28.8%) or III disease (27.8%). Median DFS was 20.1 months (CI 16.0–28.7) and median OS was 40.4 months (CI 37.3-52.5). Recurrence occurred in 64.2% of patients, and the median survival post-recurrence was 15.4 months. In gene-level analyses, alterations in SMAD4 and BRAF were significantly associated with shorter DFS (SMAD4: HR 4.2, CI 1.61-11.00, p 0.003; BRAF HR 3.89, CI 1.17-12.92, p 0.03). Mutations in SMAD4 and NTRK1/2/3 were also associated with worse OS (SMAD4: HR 3.53, CI 1.22-10.19, p 0.02; NTRK1/2/3: HR 7.72, CI 2.23 - 26.70, p 0.001), while mutations in FGFR2 significantly improved OS (HR 0.22, CI 0.05-0.92, p 0.03). Subsequently, cluster-based analysis was performed to prevent distortion from low-frequency alterations. Cluster 1 (TP53/KRAS/ATM) and cluster 2 (CDKN2A/2B) were not associated with OS or DFS. In contrast, cluster 3 (ARID1A/PBRM1/IDH1) alterations were associated with decreased OS (HR 2.36, CI 1.23-4.56, p 0.01). Cluster 4 (FGFR2/BAP1) mutations were associated with improved OS (HR 0.33, CI 0.12, 0.92, p 0.03) relative to patients without these alterations. Conclusions: In the post-surgical setting, patients harboring mutations in chromatin remodeling pathways (ARID1A/PBRM1/IDH1), as well as SMAD4 and NTRK1/2/3, experienced worse outcomes, whereas those with BAP1 and FGFR2 alterations demonstrate improved outcomes. Although limited by sample size, our study lays out the foundation for future investigations evaluating the impact of molecular profiling in BTC patients undergoing surgical resection.
Oral fluoropyrimidines as alternatives to intravenous 5-fluorouracil in combination with immune checkpoint inhibitors for recurrent metastatic head neck squamous cell carcinoma.
e18015 Background: Based on the KEYNOTE-048 trial, immune checkpoint inhibitors (ICIs) with or without chemotherapy have become the new standard for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Although pembrolizumab combined with chemotherapy—including continuous intravenous 5-fluorouracil (5-FU)—achieves higher response rates than pembrolizumab alone, prolonged hospitalization and adverse events make this regimen challenging to implement in real-world practice. Whether oral fluoropyrimidines can replace continuous 5-FU warrants further investigation. This study evaluated the efficacy of ICIs plus platinum and oral tegafur-uracil as first-line therapy for R/M HNSCC. Methods: This single-institution retrospective cohort study enrolled patients receiving ICIs combined with platinum and fluoropyrimidine-based therapy as first-line treatment. Patients were stratified according to the route of fluoropyrimidine administration: oral tegafur-uracil versus intravenous 5-FU. Propensity score matching was employed to balance baseline characteristics and pretreatment biochemical parameters. Progression-free survival (PFS) and overall survival (OS) were analysed. Results: Among 116 patients, 20.7% (N = 24) received oral therapy. Before matching, no statistically significant differences in survival were observed between groups, although outcomes numerically favored the oral cohort (PFS: 5.3 vs. 6.4 months, HR [95% CI]: 0.979 [0.524–1.829]; OS: not reached vs. 11.0 months, HR [95% CI]: 0.415 [0.165–1.309]). Recurrent T staging and neutrophil-lymphocyte ratio were independent prognostic factors for OS, with HRs [95% CIs] of 2.181 [1.276–3.726] and 2.268 [1.276–3.726], respectively. Patients with distant metastases and higher neutrophil-monocyte ratios demonstrated a superior survival benefit with oral therapy (Table 1). After 1:2 propensity score matching, survival trends persisted (PFS: 5.3 vs. 6.3 months; HR [95% CI]: 1.515 [0.619–3.712]; OS: not reached vs. 11.2 months; HR [95% CI]: 0.465 [0.133–1.619]). Conclusions: Oral tegafur-uracil demonstrated non-inferior outcomes compared to continuous intravenous 5-FU when combined with ICIs for R/M HNSCC. Prospective randomized controlled trials are warranted to confirm these findings. Hazard ratio between patients with or without oral tegafur-uracil for survival outcomes. PFS (HR, 95% CI) OS (HR, 95% CI) Distant metastasis Yes 0.618 (0.206-1.855) 0.145 (0.019-1.083) No 1.233 (0.574-2.653) 0.682 (0.240-1.937) Neutrophil-monocyte ratio Higher 0.510 (0.196-1.324) 0.189 (0.045-0.793) Lower 2.027 (0.860-4.776) 0.949 (0.279-3.236) All patients 0.979 (0.524-1.829) 0.415 (0.165-1.039)
Pre-operative chemotherapy versus surgery first with peri-operative interventions in early triple-negative and HER2-positive breast cancer: An open-label, phase 3, randomized controlled trial (PRaCTiSE).
TPS659 Background: Surgery is a mainstay of treatment of breast cancer. Neoadjuvant chemotherapy (NACT) has not proven to be more effective in improving long-term outcomes when compared with adjuvant (EBCTCG, Lancet Oncol, 2018). Although pathological complete response (pCR) is surrogate at the individual patient level, it has not translated into improved outcomes across trials (BMJ, 2021).Triple-negative (TN) and HER2-positive breast cancer patients with non-pCR are treated with risk-adapted maintenance regimens (NEJM, 2025; NEJM, 2017). We previously proved efficacy of pre-operative progesterone and intra-operative peri-tumoural lignocaine in improving disease-free and overall survival (JCO, 2011; JCO, 2023). We are currently testing the effectiveness of a “Surgery first” versus “PRe-operative ChemoTherapy” approach in patients with early TN and HER2-positive tumours. Methods: This is a prospective, open-label randomized trial. Patients with cT1c/2,cN0/1, histologically proven, TN or HER2-positive breast cancer are screened. The study is approved by Institutional Ethics and has been registered on CTRI (CTRI/2024/02/063118). Eligible patients fit for surgery and NACT are randomized after consenting. Stratification criteria are menopausal status (pre-peri/post), cN stage (N0/N1), and TN/HER2+. “Surgery first” arm receives intramuscular progesterone injection 4-14 days before surgery and peri-tumoral 0.5% lignocaine infiltration intra-operatively. All patients are treated with standard adjuvant chemotherapy and targeted therapy and radiotherapy protocols. “PRe-operative ChemoTherapy” arm receives standard NACT. Chemotherapy backbone is anthracycline, cyclophosphamide, and paclitaxel in all patients, with addition of carboplatin and pembrolizumab in NACT for TN and anti-HER2 targeted therapy (dual if node positive) in HER2+ setting. Response assessment is done clinically after each cycle and with imaging after every 3-4 cycles. Maintenance pembrolizumab/capecitabine for TN and anti-HER2 targeted therapy/t-DM1 for HER2+ tumours as per response is offered for standard duration. Surgery in both arms is breast conservation surgery with or without oncoplasty or mastectomy with or without reconstruction, depending on imaging findings, response, and patient choice. All primary tumors are clipped in NACT arm. Axillary staging procedure is carried out and, if positive macro-metastatic nodes on frozen section, level I-III axillary dissection is done. A total sample size of 1350 (1500 accounting for loss-to-follow-up) split equally between two groups, or 257 events, achieves 80% power to detect hazard rate of 0.70173 when the proportions surviving in each group are 0.78 and 0.84 at a significance level (alpha) of 0.05 using a two-sided log rank test. An interim is planned at 50% DFS events. Clinical trial information: CTRI/2024/02/063118 .
Effects of short-term fasting compared to free diet in ovarian cancer patients: Results from a two-arm pilot randomized trial.
5517 Background: Short-term fasting (STF) may enhance chemotherapy efficacy by suppressing insulin-driven pro-survival signaling. Clinical data on the metabolic, oncological, and immunological effects of STF in ovarian cancer (OC) are lacking. Methods: In this prospective, pilot randomized trial conducted at our center, women with advanced high-grade serous OC receiving carboplatin/paclitaxel-based neoadjuvant chemotherapy (NACT) were randomized to STF (36h before to 24h after each cycle) or a free diet (FD). Eligibility criteria included body mass index ≥ 19 kg/m2. Major exclusions were diabetes mellitus, food allergies, and eating disorders. The primary endpoint was insulin reduction after three NACT cycles. Secondary endpoints included oncological outcomes. Exploratory translational analyses assessed immune profiling. Based on 80% power and a two-sided α of 0.05, 17 patients per arm were required. Results: Eighteen patients per arm completed three NACT cycles. Baseline clinical characteristics and insulin levels were comparable between groups. After NACT, insulin increased in FD but decreased in STF (+9.76 vs -1.12 µIU/mL; p=0.01). Patients who did not undergo interval cytoreductive surgery (ICS) after three cycles experienced a greater insulin increase than those who underwent surgery (+11.46 vs +1.35 µIU/mL; p=0.033). At ICS, a chemotherapy response score of 3 was more frequent in STF than in FD (58.8% vs 17.6%; p=0.03). After a median follow-up of 18 months, median progression free survival (PFS) was longer in the STF arm compared with FD (38 vs 24 months; p=0.045). Translational analyses showed that STF limited immunosuppressive subsets correlated with chemotherapy response. Conclusions: The primary endpoint was met. STF induced a favourable metabolic shift and was associated with improved pathological response and prolonged PFS, alongside immune modulation. These findings provide a strong rationale for larger randomized trials evaluating STF in OC. Clinical trial information: NCT07039331 . Surgical outcomes and metabolic parameters before (baseline insulin levels) and after neoadjuvant chemotherapy (insulin levels and variation after NACT) according to the diet regimen. Free Diet Arm N=18 Short-Term Fasting Arm N=18 Overall population N=36 P value ICS Never 1 (5.6) 1 (5.6) 2 (5.6) 0.927 After III cycles 12 (66.7) 13 (72.2) 24 (66.6) After VI cycles 5 (27.7) 4 (22.2) 8 (22.2) CRS 1 5 (29.4) 1 (5.9) 6 (17.6) 0.030 2 9 (52.9) 6 (35.3) 15 (44.1) 3 3 (17.6) 10 (58.8) 13 (38.2) Insulin Level - Baseline (µIU/mL) Mean, SD 8.7 (4.99) 10.7 (7.54) 9.71 (6.38) 0.353 Insulin Level - after NACT ( µIU/mL) Mean, SD 18.5 (12.68) 9.59 (6.66) 14.03 (10.95) 0.014 Insulin Variation after NACT ( µIU/mL) Mean, SD +9.76 (12.89) -1.12 (11.0) +4.32 (13.03) 0.010 CRS, Chemotherapy Response Score; ICS, Interval Cytoreductive Surgery; NACT, Neoadjuvant Chemotherapy; SD, Standard Deviation.
Amivantamab in <i>EGFR</i> -mutated NSCLC with refractory brain or leptomeningeal metastases: A multi-center real-world study.
8521 Background: The central nervous system (CNS), particularly after progression on third-generation EGFR TKIs, represents a common yet challenging scenario. While recent trials establish amivantamab-lazertinib for EGFR-mutant NSCLC, their real-world applicability is limited by patient complexity and access barriers, highlighting an urgent need for flexible, real-world solutions. Methods: To evaluate the intracranial efficacy of amivantamab, used as monotherapy or in combination, we conducted a multi-center, retrospective study of patients with EGFR-mutated NSCLC and brain parenchymal metastases (BM) and/or leptomeningeal metastases (LM) treated with amivantamab monotherapy or combination based on routine clinical practice. The cohort included two key populations: heavily pretreated patients with sensitizing exon19del/L858R mutations after progression on third-generation EGFR TKIs, and treatment-limited patients with atypical mutations. Efficacy endpoints included intracranial progression-free survival (PFS) and intracranial objective response rate (ORR) by RANO-BM and/or RANO-LM. Exploratory endpoints included symptom improvement, and longitudinal cerebrospinal fluid (CSF) biomarker dynamics. Results: Thirty-one patients from seven centers were included (BM, n=13; BM+LM, n=18). Most (25/31, 80.6%) harbored EGFR sensitizing mutations and had progressed on third-generation EGFR TKIs; six (19.4%) carried atypical EGFR mutations. Over half (17/31, 54.8%) had received ≥4 prior lines. Amivantamab monotherapy was received in 10/31 patients (32.3%). Median intracranial PFS was 10.3 months (95% CI, 4.5-16.1). Among 24 evaluable patients, intracranial ORR was 25.0% (n=6), and disease control rate was 91.7% (n=22). CNS-related symptoms improved in 26/31 (83.9%). CSF analyses showed decreased pressure and CEA, reduced EGFR amplification, and clearance of EGFR C797S. Conclusions: In real-world settings, amivantamab-based regimens demonstrate promising intracranial efficacy in EGFR-mutated NSCLC patients with refractory brain or leptomeningeal metastases. These findings support the use of amivantamab as a viable therapeutic strategy in this challenging population and suggest that CSF biomarkers can serve as a valuable tool for monitoring treatment response.
Delayed Halide‐Rich Molecular Passivation of CsPbCl <sub>3</sub> Perovskite Nanocrystals Enables Bright Violet Light‐Emitting Diodes
ABSTRACT CsPbCl 3 perovskite nanocrystals (NCs) are promising violet emitters owing to their narrow emission and high color purity, but their low defect tolerance demands careful passivation to achieve high photoluminescence quantum yield (PLQY), and typically only for fresh CsPbCl 3 NCs. Here, we report a delayed dual‐passivation pathway in CsPbCl 3 NCs induced by the halide‐rich molecular reagent phosphorus oxychloride (POCl 3 ), which unexpectedly yields a strong time‐dependent PLQY enhancement instead of the rapid degradation usually observed. POCl 3 gradually decomposes into P‐ and Cl‐containing species, enabling a controlled release of excess halides that autonomously passivates halide vacancies in a self‐regulated manner. This dynamic self‐healing process boosts the PLQY of colloidal CsPbCl 3 NCs by over 40‐fold relative to pristine samples and sustains high violet emission efficiencies for more than 2 months of storage under ambient conditions. Spectroscopic measurements and calculations indicate that both liberated Cl − and in situ—formed phosphonic species passivate halide vacancies and Pb 2 + dangling bonds, suppressing mid‐gap defect states. The resulting self‐passivated NCs deliver a luminance of 409 cd m − 2 , the highest reported for CsPbCl 3 ‐based violet emitters. These results establish halide‐rich dual passivators such as POCl 3 as powerful tools for long‐term defect control in chloride perovskite NCs and for robust, bright violet‐LEDs.
Oxygen Vacancy‐Engineered CaCu <sub>3</sub> Ti <sub>4</sub> O <sub>12</sub> Nanocatalyst for Piezoelectrically Driven Cascade Apoptosis/Cuproptosis/Ferroptosis Therapy
ABSTRACT Ultrasound (US) induced piezoelectric catalytic therapy is an emerging cancer treatment method. However, the development and optimization of piezoelectric catalyst remain the major challenge. Herein, we have converted the classical dielectric material CaCu 3 Ti 4 O 12 (CCTO) into an efficient piezoelectric material through oxygen vacancy (V O ) engineering, enabling piezoelectric catalytic‐driven cascade tumor therapy. The introduction of V O results in strong polarization and a robust piezoelectric coefficient. Density functional theory (DFT) calculations reveal that V O acts as an electron trap to suppress the recombination of electron and hole, enhancing the catalytic efficiency. The piezoelectric effect can “open” the cell membrane, facilitating the materials influx and triggering reactive oxygen species (ROS) storm. Meanwhile, the cavitation effect of US and tumor cell over‐expressed glutathione (GSH) accelerate Cu and Ca release, causing intracellular ions overload. ROS and Ca ions damage mitochondria to evoke apoptosis, which accordingly shuts down the Cu + outflow pathway and expedites cuproptosis. Moreover, ROS and GSH depletion triggers ferroptosis. This process establishes a positive feedback loop mechanism. Transcriptome sequencing confirms the activation of cell death‐related pathways. This study represents the first paradigm to create piezoelectricity through V O in CCTO for tumor therapy, advancing the applications of quadruple perovskites in tumor treatment.
Electrostatically Driven Size‐Sieving of Carbon Dioxide From Acetylene Enabled by a Cation‐Gated Molecular Sieve
ABSTRACT Developing molecular sieves is vital, energy‐saving, but very challenging for gas separations in the petrochemical industry. Current molecular sieves reported for inverse CO 2 /C 2 H 2 separation are very scarce and suffer from low CO 2 capacity and poor diffusion within the restricted nanopores. Herein, we report an electrostatically driven size‐sieving of CO 2 from C 2 H 2 in a porous cation‐gated molecular sieve (Na‐RHO) with high CO 2 capacity and fast diffusion. Na‐RHO features large pore cavities (10.7 Å) interconnected by small Na + ‐gated pore windows (3.4 Å), in which the Na + ‐gated pore windows enable a complete size‐exclusion of C 2 H 2 due to the electrostatically driven sieving effect, and large pore cavities provide enough pore spaces to take up large amount of CO 2 with fast diffusion. Such an electrostatically driven molecular‐sieving mechanism for Na‐RHO was studied by gas sorption isotherms and theoretical calculations, leading to both the record‐high CO 2 /C 2 H 2 selectivity (3.35 × 10 6 ) and CO 2 uptake capacity (188.0 cm 3 cm −3 ) at ambient conditions. Breakthrough experiments show that Na‐RHO can directly separate CO 2 impurity from CO 2 /C 2 H 2 mixtures, with the highest dynamic selectivity (70.4) and C 2 H 2 productivity (150.6 L kg −1 ) by far. This work provides a new strategy for designing more efficient molecular sieves with high gas capacity and diffusion for gas separations.
Guideline-concordant cancer screening among U.S. adults with and without cardiovascular risk factors.
e22565 Background: Uptake of age- and sex-appropriate cancer screening remains suboptimal in the United States. Patients with cardiovascular risk factors have increased direct cancer risk through shared behavioral, environmental, and inflammatory pathways. However, these patients may also have more frequent touchpoints with the health care system for management of their CV conditions, raising opportunities for appropriate cancer screening. Thus, we evaluate whether individuals with CV risk factors have higher rates of guideline-concordant cancer screening compared with those without such risks. Methods: We analyzed pooled 2018–2024 data from the National Health Interview Survey, restricting the sample to adults without a prior history of cancer. CV risk was defined by the presence of one or more of the following conditions: coronary heart disease, high cholesterol, congenital heart disease, diabetes, prior myocardial infarction, hypertension, or other heart disease. Outcomes included receipt of age- and sex-appropriate cancer screening (mammography, prostate-specific antigen (PSA) testing, and colonoscopy), determined according to U.S. Preventive Services Task Force recommendations. Covariates included health insurance status, private insurance, and family cancer history. Sample weights were applied to account for complex survey design. Multivariable logistic regressions were estimated for each sample. Results: Unweighted sample sizes were as follow: mammography (9,390), PSA (3,723), and colonoscopy (16,080). Survey-weighted rates of cardiovascular risk factors for each sample of screening-eligible individuals were as follow: mammography (67.8% [SE: 1.72]), PSA (82.5% [1.97]), and colonoscopy (74.8% [1.20]). In multivariable regression models, having CV risk factors was not significantly associated with increased cancer screening: mammography (OR: 1.09, p: 0.25), PSA (OR: 1.49, p: 0.19), and colonoscopy (OR: 1.03, p: 0.73). Conclusions: In this nationally representative study, cardiovascular risk factors were not associated with higher rates of guideline-concordant mammography, PSA testing, or colonoscopy. These findings suggest that chronic cardiovascular care does not consistently facilitate cancer screening, potentially due to competing clinical priorities and fragmented care. However, given continued shared risk factors, integrating cancer screening into cardiovascular disease management may represent an important opportunity to improve preventive care delivery.
Maintenance pegylated liposomal doxorubicin (PLD) versus active surveillance for advanced soft tissue sarcoma patients who had controlled disease after standard anthracycline-based treatment (MELODY).
TPS11596 Background: The progression-free survival (PFS) associated with first-line chemotherapy for advanced soft tissue sarcoma (STS) remains unsatisfactory. Extending treatment with an active agent that has demonstrated clinical benefit in a patient (pt)—the maintenance therapy—may offer an opportunity to further delay disease progression. While anthracyclines are the current standard first-line treatment, their cumulative cardiotoxicity limits prolonged use. Pegylated liposomal doxorubicin (PLD) offers a more favorable cardiac safety profile, representing a viable option for extended treatment. Methods: MELODY is a randomized, multinational clinical trial designed to evaluate the clinical benefit of maintenance PLD in pts with advanced STS who have achieved disease control following anthracycline-based therapy. The study incorporates patient-reported outcomes (PROs) to explore the balance between extended treatment and active surveillance from the patient’s perspective—providing a more holistic understanding of the value of maintenance therapy in this population. Built-in translational studies aim to identify biomarkers that better select pts most likely benefit from maintenance therapy, thereby further personalizing treatment strategies in advanced STS. Eligible criteria include advanced STS patients aged ≥ 18 who had either CR, PR, or SD after first-line anthracycline-based therapy (at least five cycles). Pts will be randomized 2:1 to the experimental arm: PLD (40 mg/m² every 28 days, up to 12 cycles) or the control arm: active surveillance. The primary endpoint is progression-free survival (PFS) post randomization. Patients in the active surveillance arm will not crossover to PLD upon progression. Secondary endpoints include QoL by EORTC C30 questionnaire, OS, 12-month PFS rate, ORR by RECIST 1.1, and time to next treatment. Left ventricular ejection fraction (LVEF) change will be an interest of safety. Exploratory objectives include efficacy endpoints (PFS, OS, 12-month PFS rate) based on circulating tumor DNA (mandatory) and FDG PET/CT SUVmax (Optional). Based on our systematic review (Lee MJ et al. Ther Adv Med Oncol 2025), the mPFS for the control arm is estimated to be 4 months. A clinically meaningful improvement is anticipated in the experimental arm, with a mPFS of 8 months. Assuming 80% power and an alpha level of 0.1, a total of 63 evaluable subjects are required. Accounting for an anticipated 20% drop-out rate, MELODY plans to enroll a total of 81 subjects. Clinical trial information: NCT06981637 .
Texture and color enhancement imaging (TXI) for polyp detection in colorectal neoplasia screening: A meta-analysis of randomized controlled trials.
10582 Background: Colonoscopy remains the gold standard for preventing colorectal cancer; however, variable adenoma detection rates (ADR) among endoscopists highlight the need for improved visualization technologies. Texture and Color Enhancement Imaging (TXI) is a novel image-enhanced endoscopy modality designed to optimize the visibility of mucosal lesions by enhancing surface texture and brightness. This meta-analysis evaluates the efficacy of TXI compared to standard high-definition white-light imaging (HD-WLI) in the detection of colorectal neoplasia, specifically assessing whether enhanced visualization translates to higher detection rates of adenomas and polyps in a randomized controlled setting. Methods: We conducted a systematic review and meta-analysis of prospective randomized controlled trials (RCTs) published between 2023 and 2025. The analysis included adult patients undergoing colonoscopy for screening, surveillance, or diagnostic indications where TXI was compared to HD-WLI during the withdrawal phase. Primary outcomes included ADR, polyp detection rate (PDR), and adenomas per colonoscopy (APC). Secondary outcomes included polyps per colonoscopy (PPC) and flat lesion detection. Statistical analysis was performed using a random-effects model (DerSimonian-Laird method). Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were calculated, with heterogeneity assessed via I² statistics. Results: The analysis pooled data from four RCTs comprising 2,308 patients. The chief finding was a statistically significant 25.5% increase in the Polyp Detection Rate (PDR) with TXI compared to WLI (pooled RR = 1.255; 95% CI: 1.050–1.498; p < 0.05). Regarding the Adenoma Detection Rate (ADR), TXI showed a positive trend with a 22% relative increase (pooled RR = 1.220; 95% CI: 0.981–1.519); however, this did not reach statistical significance (p > 0.05). Analysis of Adenomas per Colonoscopy (APC) showed no significant difference (MD = 0.153; p > 0.05). Substantial heterogeneity was observed across outcomes (I² > 60%), suggesting variability in endoscopist experience or study populations. Conclusions: Texture and Color Enhancement Imaging demonstrates clear superiority over white-light imaging for overall polyp detection, establishing it as a promising tool for identifying colorectal neoplasia. While TXI significantly improved PDR, the improvement in ADR showed a strong positive trend that did not reach statistical significance, likely due to high between-study heterogeneity. These findings suggest that TXI enhances lesion visibility, particularly for general polyps, but further large-scale RCTs are necessary to definitively establish its impact on adenoma detection and long-term interval cancer prevention.
Exploring improved prognostication using PET/CT radiomics in relapsed/refractory, TP53-aberrant diffuse large B-cell lymphoma (DLBCL).
7070 Background: Patients (pts) with TP53-aberrant DLBCL have inferior progression-free survival (PFS) and overall survival (OS) compared to pts with wild type disease, and outcomes are worse for those with R/R disease. Improved prognostics are needed to identify those at risk for inferior outcomes to guide enhanced surveillance and early initiation of subsequent therapy. Methods: Retrospective data from pts with R/R, TP53-aberrant DLBCL treated at the University of Colorado system with 2 distinct PET/CT scans at time of R/R diagnosis and post-treatment between 2016 and 2025 were included in this analysis. PET/CT measurements were conducted by two nuclear medicine physicians blinded to outcomes and included SUVmax, total metabolic tumor volume (TMTV) by 41% SUVmax method, and total lesional glycolysis (TLG). Receiver operator curves (ROC) were constructed to determine the optimal cutoff points for PFS at 1 year using Youden’s J statistic. Survival analysis was conducted using Kaplan-Meier and Cox analyses. Results: The 22 pts had a median age of 66.9 years (44-83), median follow-up of 18.7 months (mos.), and a median OS of 28.7 mos. (95% CI 19.0 – 53.8) from R/R diagnosis. 17/22 (77%) pts had primary refractory disease, 7/22 (32%) had bulky disease, 13/22 were GCB, and 8/22 (36%) had double-hit lymphoma. 17/22 pts received CAR-T therapy as next line of therapy, and OS was not associated with therapy type or line by Cox regression. ROC analysis for PET/CT interval changes from R/R diagnosis to post-treatment identified cutoffs of 86.7% for ∆SUVmax, 93.43% for ∆TMTV, and 97.98% for ∆TLG. The known prognostic ∆SUVmax >70% was associated with better OS with hazard ratio (HR) of 0.307 (p=0.025). Each radiomic metric was independently associated with superior PFS (Table 1). R-IPI >3 at progression was not associated with differences in PFS or OS (p=0.751 and p=0.655, respectively). Pts with 2 or more high-risk PET/CT radiomic features (any combination of 2+ makers less than the cutoffs) was associated with inferior PFS (Table 1), OS (HR=0.265, p=0.009), and had a median PFS of 3.5 months and OS of 19.0 months. Conclusions: PET/CT radiomic metrics were independently associated with PFS and OS in R/R, TP53-aberrant DLBCL pts. Pts with 2 or more high-risk PET/CT features were at high risk for progression and inferior OS compared to those with ≤ 1, and this 2-component model significantly outperformed R-IPI for predicting PFS and OS in this exploratory analysis, which warrants validation in future study. Median PFS Median OS HR for PFS (95% CI, p-value) ∆ SUVmax ≥ 86.7% NR 50.1 months 0.259 (0.078-0.861, p=0.0164) ∆ TMTV ≥ 93.43% NR 46.3 months 0.294 (0.085-1.03, p=0.0223) ∆ TLG ≥ 97.98% NR 46.4 months 0.223 (0.066-0.758, p=0.0071) ≥2 high-risk PET/CT features 3.5 months 19.0 months 0.181 (0.055-0.591, p=0.0012) High-risk IPI (3 or higher) 36.7 months 28.6 months 1.207 (0.341-4.279, p=0.751)
The expansion of hematopoietic cell transplantation in patients aged >75 years: A CIBMTR analysis, 2019–2023.
e13769 Background: Hematopoietic cell transplantation (HCT) is increasingly utilized in older adults; however, patients aged > 75 years have historically been excluded due to concerns regarding frailty and treatment-related toxicity. Advances in supportive care and reduced-intensity conditioning (RIC) have challenged these paradigms, prompting evaluation of real-world HCT utilization in the super-elderly population. Methods: We analyzed aggregate Center for International Blood and Marrow Transplant Research (CIBMTR) data for U.S. HCT recipients aged > 75 years between 2019 and 2023. Transplant activity was summarized by donor type, cell source, disease indication, and state. Temporal trends were assessed descriptively and modeled using Poisson regression, with results reported as incidence rate ratios (IRRs) and 95% confidence intervals. State-level transplant volumes were aggregated to assess geographic distribution. Results: Between 2019 and 2023, 1,670 HCTs were performed in patients aged > 75 years. Peripheral blood stem cells (PBSC) constituted the dominant graft source for both autologous and allogeneic transplantation throughout the study period, with minimal and stable use of bone marrow and cord blood. HCT utilization increased significantly over time(IRR 1.32 per year; p < 0.001). After adjustment for calendar year, autologous transplantation was associated with higher utilization compared with allogeneic transplantation. Disease-specific modeling demonstrated disproportionate utilization among plasma cell disorders, myelodysplastic diseases (MDS), acute myeloid leukemia(AML), and non-Hodgkin lymphoma(NHL)(Table 1). Geographic analysis revealed concentration of activity, with California, New York, and Texas accounting for 31% of all transplants. Conclusions: Real-world utilization of HCT in patients aged > 75 years is accelerating, particularly within plasma cell disorders and myeloid malignancies, challenging historical age cutoffs. This expansion, facilitated by adoption of RIC and PBSC-based platforms, reflects a safety-conscious evolution in expanding access to older candidates. However, persistent geographic disparities necessitate broader access, particularly in states with aging populations. Integrating aging domains (frailty, cognition) into registries is critical to distinguish candidates benefiting from HCT versus those at risk for functional decline. Poisson regression analysis of HCT utilization in adults aged >75 years (2019–2023). Category Poisson IRR (95% CI) p Value Overall (per year) 1.32 (1.27–1.37) <0.001 Autologous vs allogeneic 1.15 (1.04–1.26) 0.005 Plasma cell disorders 71.2 <0.001 AML 18.2 <0.001 MDS 16.5 <0.001 NHL 16.0 <0.001 Acute leukemia, other, served as the reference category for disease-specific analyses. IRRs represent relative utilization compared with the reference group.