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Neoadjuvant camrelizumab with chemotherapy (NACI) in PD-L1-negative locally advanced cervical cancer: An open-label, multi-center, single-arm, phase 2 trial.
e17510 Background: Locally advanced cervical cancer (LACC) remains associated with suboptimal outcomes with conventional therapies. We previously demonstrated substantial efficacy of neoadjuvant chemo-immunotherapy (NACI) in PD-L1–positive LACC, achieving an objective response rate (ORR) of 97.6%, a pathologic complete response (pCR) rate of 37.6%, and a 3-year event-free survival (EFS) of 95.1% (95% CI, 90.6–99.9), with overall survival (OS) of 96.8% (95% CI, 92.3–100). Emerging evidence suggests immune checkpoint inhibition may also benefit PD-L1–negative disease. This phase II trial evaluated the efficacy and safety of NACI in PD-L1–negative LACC, an underrepresented population with limited treatment options. Methods: This open-label, multicenter, single-arm phase II trial (NCT06288360) enrolled treatment-naïve patients with PD-L1–negative cervical cancer (combined positive score <1), FIGO 2018 stage IB3, IIA2, IIB, or IIIC1r, and tumor size >4 cm. Patients received one cycle of induction chemotherapy with cisplatin plus nab-paclitaxel, followed by two cycles of camrelizumab combined with cisplatin and nab-paclitaxel. Tumor response was assessed per RECIST v1.1, with ORR defined as complete or partial response. Responders underwent radical hysterectomy with pelvic lymphadenectomy, while non-responders received definitive chemoradiotherapy. The primary endpoint was pCR rate; secondary endpoints included ORR, surgical feasibility, safety, and survival. Simon’s two-stage design was applied, with a planned sample size of 40 patients; stage II required at least two responses among the first 14 evaluable patients. Results: Between September 12, 2024 and December 12, 2025, ten patients were enrolled. Nine completed NACI; all achieved an objective response (ORR 100%) and underwent radical hysterectomy, with an R0 resection rate of 100%. Three patients achieved pCR. Among six non-pCR patients, four had no Sedlis-defined intermediate-risk factors and were managed with surveillance. Parametrial invasion (n=1) and lymph node metastasis (n=1) were identified, and both patients received adjuvant chemoradiotherapy. The predefined stage I efficacy criterion was met, enabling progression to stage II. No treatment-related deaths or delays occurred. The most common grade ≥3 immune-related adverse event was lymphocytopenia. Conclusions: Preliminary interim results indicate that neoadjuvant camrelizumab plus chemotherapy shows promising antitumor activity, excellent surgical feasibility, and acceptable safety in PD-L1–negative LACC. While long-term survival and quality-of-life outcomes are pending, these findings support further investigation of chemo-immunotherapy as a neoadjuvant strategy for low-risk LACC regardless of PD-L1 expression status. Clinical trial information: NCT06288360 .
Clinically actionable TURBT-derived bladder cancer organoid pharmacotyping as a predictor of postoperative outcomes in a prospective multicenter study.
e16613 Background: Post-TURBT chemotherapy is largely empiric despite marked inter-patient heterogeneity in bladder cancer drug sensitivity. We evaluated a multicenter TURBT-derived PDO pharmacotyping workflow and its concordance with postoperative outcomes. Methods: In a prospective multicenter study (NCT06662071), TURBT bladder cancer specimens were used to generate patient-derived organoids (PDOs), with histologic fidelity assessed by H&E and immunohistochemistry (CK5/6, CK7, CK20, Ki-67, p53, p63). PDOs underwent 3D drug testing (serial dilutions; 72-hour exposure) across eight clinically used agents/regimens; viability (CellTiter-Glo 3D) was used to derive IC50 and nAUC (plus viability at Cmax). Six response-classification strategies (Jenks vs tertiles × IC50/nAUC/Cmax viability) were compared, and concordance with postoperative chemotherapy outcomes (recurrence/progression on surveillance follow-up) was summarized by specificity and accuracy. Results: From 4 centers, 63 TURBT specimens yielded 41 PDO lines from 37 patients (65.1% success). Successful establishment correlated with higher post-digestion viability (p < 0.01) and cell yield (p < 0.05). Drug profiling was completed in 35/41 lines (85.4%). IC50 values spanned submicromolar medians for anthracyclines/pirarubicin (pirarubicin 0.080 µM; doxorubicin 0.540 µM; epirubicin 0.508 µM) to higher micromolar medians for platinum/antimetabolites (cisplatin 20.245 µM; gemcitabine 16.913 µM; methotrexate 61.205 µM), with gemcitabine showing the widest range (0.004–369.500 µM). Of six strategies, IC50-based Jenks natural breaks (Sensitive/Intermediate/Resistant) best matched clinical outcomes (specificity 0.933; accuracy 0.882). Clinical concordance was assessed in 15 treated patients (17 PDO–patient pairs); 2/15 (13.3%) recurred/progressed. Illustrative concordant cases included pirarubicin sensitivity (IC50 0.12 µM) with recurrence-free follow-up and gemcitabine resistance (IC50 227.7 µM) with early recurrence/progression after GC-based management. Conclusions: This multicenter TURBT-derived bladder cancer PDO study establishes a clinically actionable pharmacotyping workflow. PDOs can be generated from routine specimens, capture marked inter-patient drug-response heterogeneity, and provide drug-specific sensitivity tiers that align with postoperative outcomes with high specificity for identifying potentially ineffective therapy. These data support prospective validation of PDO-guided regimen selection to reduce futile treatment and individualize postoperative bladder cancer care.
Clinical outcomes of muscle-invasive and metastatic, bladder, and urethral pure adenocarcinoma (BUAdenoCa): An international study from the Global Society of Rare Genitourinary Tumors (GSRGT).
e16565 Background: BUAdenoCa are rare and their management options are limited. The GSRGT assembled an international cohort of pts with BUAdenoCa to evaluate the natural history and clinical outcomes of this rare cancer in the perioperative and metastatic settings. Methods: We retrospectively collected data on pts with locally advanced or metastatic BUAdenoCa receiving systemic therapy between 2000-2026 at 25 medical centers in the US, Europe, South America, and Asia. Median overall survival (mOS), disease-free survival (mDFS), and progression free survival (mPFS) were estimated by the Kaplan-Meier method for perioperative and metastatic pts. Observed objective response rate (ORR) was determined for metastatic pts receiving systemic therapy by the clinical investigator per RECIST v1.1 criteria when feasible. Results: Among 328 pts with BUAdenoCa, including urachal (47%), urethral (11%), and non- urachal-nonurethral bladder AdenoCa /other (42%). Median age was 61 years; 61% were male; 68% were White, 17% were Black, 12% were Asian; 87% were non-Hispanic. At time of study, most patients were metastatic (65%), followed by muscle-invasive/locally advanced (16%), and non-muscle-invasive/NED (19%). 80% of stage IV pts had visceral metastases, including lung (44%), bone (36%), and liver (17%), while 10% had LN-only disease. Other metastatic sites included peritoneal/mesentery, gynecologic organs, soft tissue, muscle, CNS, and other abdominal or retroperitoneal locations. Among pts with molecular data, 98% were microsatellite stable. Common alterations included TP53 (18%), KRAS (9%), and SMAD4 (5%). Clinical outcomes by type and treatment setting are summarized in the Table. Conclusions: To date, this represents the largest retrospective analysis of BUAdenoCa. These data suggest outcomes differ by type of BUAdenoCa and there is an association between 5-FU based therapy and improved outcomes in both the perioperative and metastatic settings. Analysis Cohort Variable mDFS / mPFS (yrs) mOS (yrs) ORR (% [n/N]) Median DoR (months) Surgery ± perioperative systemic therapy (n=220) Urachal 1.5 6.3 — — Urethral 1.0 4.2 — — Other BUAdenoCa 1.8 3.2 — — 5-FU–based 2.7 NR — — Non–5-FU 2.0 2.7 — — Metastatic 1L systemic therapy (n=138) Urachal 0.68 2.3 — — Urethral 0.37 2.9 — — Other BUAdenoCa 0.54 1.6 — — 5-FU–based 0.64 2.3 29.3% (24/82) 6.8 Non–5-FU 0.57 1.5 22.5% (11/49) 8.7
Does surgery improve breast cancer–specific survival in low-grade DCIS?: A 20-year population-based analysis by nuclear grade.
578 Background: Active surveillance is increasingly discussed for low-risk ductal carcinoma in situ (DCIS), yet randomized trials report only short-term outcomes. Long-term survival data stratified by nuclear grade remain limited. We evaluated the association between cancer-directed surgery and long-term breast cancer–specific survival (BCSS) and overall survival (OS) in DCIS. Methods: We conducted a retrospective population-based cohort study using SEER 17 registries, including patients diagnosed with DCIS between 2000 and 2019 with follow-up exceeding 36 months. Exposure was cancer-directed surgery (yes vs no). Outcomes were BCSS, analyzed using cause-specific Cox models, and OS. Prespecified covariates included age, year of diagnosis, race, tumor size, nuclear grade, estrogen and progesterone receptor status, median household income, and residence type. Missing data were handled using multiple imputation. Confounding was addressed using inverse probability of treatment weighting with stabilized weights. Analyses were stratified by nuclear grade (Grades 1–3). Results: Among 51,637 patients, 50,346 (97.5%) underwent surgery and 1,291 (2.5%) did not. Median follow-up was 120 months. In the overall cohort, surgery was associated with improved BCSS (hazard ratio [HR] 0.13; 95% CI, 0.09–0.19) and OS (HR 0.65; 95% CI, 0.56–0.75). Outcomes differed substantially by nuclear grade. In Grade 1 DCIS, surgery was not associated with improved BCSS (HR 0.57; 95% CI, 0.05–6.16), with 20-year BCSS exceeding 99% regardless of treatment, although OS favored surgery. In Grade 2 DCIS, surgery reduced breast cancer–specific mortality (HR 0.22; 95% CI, 0.10–0.45) without an OS benefit. In Grade 3 DCIS, surgery conferred marked improvements in both BCSS (HR 0.10; 95% CI, 0.06–0.15) and OS (HR 0.49; 95% CI, 0.40–0.60). Conclusions: In this large population-based study with up to 20 years of follow-up, omission of surgery in low-grade DCIS was not associated with worse breast cancer–specific survival, whereas clear survival benefits were observed in intermediate- and high-grade disease. These findings support risk-adapted management strategies and provide long-term survival context for active surveillance approaches in DCIS.
Baseline CT-derived QVT score as predictor of bevacizumab benefit in advanced non-squamous NSCLC: A retrospective biomarker analysis of SWOG S0819.
8549 Background: Despite two decades of anti-angiogenic therapy in NSCLC, no predictive biomarker identifies which patients benefit. As VEGF-targeted combinations advance in clinical development, patient selection biomarkers remain a critical unmet need. QVT (Quantitative Vessel Tortuosity) Score is an automated imaging biomarker measuring chaotic tumor vasculature from baseline CT scans and has been shown to be associated with immune checkpoint inhibitor (ICI) outcomes. We hypothesized that QVT Score could identify patients with chaotic angiogenesis tumors and greater sensitivity to anti-angiogenic therapy. Methods: We analyzed a subset of 334 patients from the SWOG S0819 (NCT00946712) trial with treatment-naïve stage IV non-squamous NSCLC receiving carboplatin/paclitaxel with (56%) or without (44%) bevacizumab. QVT Scores were derived from baseline CTs based on radiologist-defined tumor annotations and radiomic features of tumor vasculature (e.g. vessel twisting, curvature, and branching). Overall survival (OS) was evaluated as the primary endpoint using Cox proportional hazards models with QVT × bevacizumab interaction terms. Bevacizumab was non-randomized in S0819 (physician/patient discretion): to address this, we employed doubly robust estimation combining inverse probability of treatment weighting (IPTW) with multivariable covariate adjustment for age, performance status, histology, smoking history, and stage. Results: The QVT Score × bevacizumab interaction was significant (p=0.007, doubly robust estimation) and stayed consistent across sensitivity analyses (p=0.017 multivariable; p=0.047 IPTW), suggesting differential treatment benefit based on pre-treatment vascular phenotype. QVT Score was strongly OS-associated without bevacizumab (HR=3.03, p=0.003) but not with bevacizumab (HR=1.71, p=0.079), consistent with mitigation of high-risk biology. Bevacizumab benefit increased across QVT quartiles (Table 1): patients in the highest quartile had a 60% reduction in mortality (HR=0.40, p<0.001), while patients in the lowest quartile showed no OS benefit (HR=0.89, p=0.64). Conclusions: Despite unfavorable prognosis on standard-of-care therapies (chemotherapy, ICIs), we found that patients with elevated baseline QVT Score may benefit from the addition of anti-angiogenic agents. As VEGF-targeted combinations including bispecific antibodies enter development, radiomic biomarkers may play a crucial role in enriching trial populations and enabling mechanistic longitudinal monitoring. These findings warrant prospective validation in independent randomized clinical trials. Bevacizumab treatment effect by QVT score quartile. QVT Score Quartile N Bevacizumab effect (Hazard Ratio) P Q1 84 0.89 (0.56 -1.42) 0.64 Q2 83 0.70 (0.44-1.12) 0.14 Q3 83 0.54 (0.34-0.85) 0.01 Q4 84 0.40 (0.24-0.65) 0.0003
Osimertinib combined with bevacizumab and chemotherapy as 1L treatment in EGFR-mutated metastatic non-squamous non-small cell lung cancer (nsq NSCLC) with concurrent mutations.
8625 Background: Concurrent mutations in EGFR sensitive mutations (19 del/21 L858R) are associated with poor prognosis. Previous studies have shown that EGFR-TKI combined with chemotherapy or anti-angiogenic drugs confers heterogeneous degrees of benefit in this population. However, the efficacy of concurrent EGFR-TKI, anti-angiogenic agent, and chemotherapy has not been reported. Methods: This is a single-center, open-label, phase I clinical trial designed to evaluate the efficacy and safety of osimertinib combined with bevacizumab and chemotherapy as first-line treatment for EGFRm metastatic nsq NSCLC with concurrent mutations (NCT05507606). 4 induction cycles will be administered (Osimertinib, 80 mg/d, d8–21; bevacizumab, 7.5 mg/kg, d1; pemetrexed 500 mg/m², d1; and carboplatin AUC 5, d1; 3 week/cycle), after which carboplatin will be discontinued. Osimertinib combined with bevacizumab and pemetrexed will be continued as maintenance (Osimertinib, 80 mg/d, d1–21; all other remained unchanged). Bevacizumab and pemetrexed will be stopped at 2 years; osimertinib will be continued until disease progression. EGFRm include exon 19 del, L858R, T790M, G719X, L861Q, S768I, exon 20 A763–Y764 insertion, and concurrent mutations are defined as the presence of at least one destructive TP53 mutation in exons 5 to 8. The primary endpoints are safety and objective response rate (ORR). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Exploratory endpoints comprise NGS comparative analysis pre-/post-treatment, 19 del/L858R subgroup analysis, ctDNA clearance, and the correlation between efficacy and prognosis. Results: 34 patients were enrolled. Males accounted for 29.41%, and the median age was 58.5 years (25-75). Patients with ECOG PS 1 and 2 comprised 97.1% and 2.9%, respectively. The EGFRm profile consisted of 19 del (50.0%), L858R (44.1%), and other mutations (5.9%, including 20 ins and L861Q). All patients have finished the 4 induction cycles. The median follow-up was 36.8 months (95% CI, 24.2–47.4). The ORR was 94.12% (95% CI, 80.32%–99.28%), the DCR was 100% (95% CI, 89.72%–100%). The median PFS and OS were 35.9 m (95% CI, 26.0–NR) with 44.1% maturity and NR with 26.5% maturity, respectively. 19 del: ORR 100%, PFS/OS NR. L858R: ORR 86.7%, mPFS 26.5m (95%CI:16.3-NR), mOS 47.8m (95%CI:22.1-NR). Others: ORR 100%, mPFS 10.8m (95%CI:7.9-NR), mOS 21.1m (95%CI:18.2-NR). Grade ≥ 3 AE occurred in 31.25% of patients during the induction phase. No deaths related to toxicity were observed. The discontinuation rate was 9.4%; no patient discontinued treatment because of AE. Conclusions: These results demonstrate that the four-drug regimen anchored by osimertinib is well tolerated and active in patients with EGFRm metastatic nsq NSCLC harboring concurrent mutations. Clinical trial information: NCT05507606 .
Epidemiological trends and burden of pancreatic cancer in the United States: A retrospective analysis from 1990 to 2023 with advanced machine learning forecasting to 2050.
e16402 Background: Pancreatic cancer remains a leading cause of cancer-related burden in the United States, with persistently high mortality and limited survival gains despite advances in diagnostics and treatment. This study analyzed age-standardized rates (ASRs) of DALYs, deaths, incidence, and prevalence from 1990 to 2023 using IHME GBD 2023 data, assessed trends via estimated annual percentage change (EAPC), and projected future burden to 2050 with ARIMA forecasting. Methods: Age-standardized rates per 100,000 population were extracted from the Global Burden of Disease 2023 database for the United States, stratified by sex (Both, Female, Male). Historical trends (1990–2023) were evaluated using EAPC derived from linear regression on log-transformed ASRs. Future projections (2024–2050) employed ARIMA models fitted to historical time series, generating point forecasts and 95% prediction intervals (PI). Results: From 1990 to 2023, age-standardized DALYs (Both sexes) fluctuated between 201.4 (1997) and 214.4 (2015–2016), with an overall EAPC of 0.16% (95% CI: 0.13–0.20). Females showed a higher increase (EAPC 0.20%, 95% CI: 0.17–0.23) than males (EAPC 0.09%, 95% CI: 0.05–0.13). Age-standardized death rates rose modestly (Both: EAPC 0.27%, 95% CI: 0.24–0.31; from ~8.95 in 1990 to ~9.56 in 2023), with similar sex patterns (Female EAPC 0.28%, Male 0.22%). Incidence exhibited the strongest historical growth (Both: EAPC 0.31%, 95% CI: 0.27–0.36; Female 0.34%, Male 0.25%), increasing from 9.65 (1990) to 10.53 (2023). Prevalence increased most rapidly (Both: EAPC 0.50%, 95% CI: 0.42–0.58), reflecting slightly better short-term survival. ARIMA forecasts indicate a gradual decline in age-standardized DALYs (Both: from 211.2 in 2024 to ~192.2 in 2050; 95% PI narrowing around downward trend), deaths (Both: from ~9.64 to ~10.16, but with widening intervals suggesting uncertainty), and incidence (Both: stabilizing then slight rise to ~11.24 by 2050), while prevalence continues upward to ~12.57 by 2050 due to aging population and modest survival gains. Conclusions: Pancreatic cancer burden in the US showed modest increases in age-standardized rates from 1990–2023, driven primarily by incidence and prevalence rises, with forecasts to 2050 predicting stabilization or slight declines in DALYs and mortality rates amid ongoing demographic pressures. These projections underscore the urgent need for improved prevention, early detection, and therapeutic innovations. Measure Sex EAPC Lower 95%CI Upper 95%CI DALYs Both 0.16 0.13 0.2 DALYs Female 0.2 0.17 0.23 DALYs Male 0.09 0.05 0.13 Deaths Both 0.27 0.24 0.31 Deaths Female 0.28 0.25 0.31 Deaths Male 0.22 0.18 0.26 Incidence Both 0.31 0.27 0.36 Incidence Female 0.34 0.31 0.38 Incidence Male 0.25 0.2 0.3 Prevalence Both 0.5 0.42 0.58 Prevalence Female 0.58 0.51 0.66 Prevalence Male 0.4 0.32 0.48
Clinical impact of R0 resection after chemotherapy in initially unresectable metastatic colorectal cancer: A pooled analysis of the ARCAD database.
e15557 Background: In metastatic colorectal cancer (mCRC), systemic chemotherapy can enable conversion surgery in a subset of patients with initially unresectable disease. Although R0 resection considered a key determinant of long-term survival, its clinical impact across heterogeneous trial populations and treatment strategies remains insufficiently defined. We aimed to clarify the survival benefit of R0 resection after first-line chemotherapy using large-scale individual patient data. Methods: Using the ARCAD database, which comprises 67 randomized clinical trials and approximately 47,000 patients, we conducted a pooled analysis of individual patient data from six first-line randomized clinical trials (COIN, COIN-B, 03-TTD-01, ATOM, SOFT and PARADIGM) for which data on R0 resection were available. Patients with initially unresectable mCRC and available surgical data were categorized into three groups: R0 resection, non-R0 resection, and no surgery. All R0 cases were included, comprising liver-only, lung-only, combined liver and lung metastases, and peritoneal dissemination or other metastatic sites. Overall survival (OS) and progression-free survival (PFS) were evaluated using multivariable Cox proportional hazards models adjusted for age, sex, and performance status. Pre-specified subgroup analyses examined the consistency of outcomes according to tumor response, metastatic site, primary tumor sidedness, RAS status, and targeted therapy class. Results: Among 4,445 eligible patients, 263 underwent R0 , 233 underwent non-R0 resection, and 3,949 received no surgical intervention. The R0 resection group comprised patients with liver-only metastases (n = 176), lung-only metastases (n = 23), and combined liver and lung metastases (n = 27). R0 resection was associated with significantly improved OS and PFS compared with both non-R0 resection and no surgery. These survival benefits were consistently observed across key clinical subgroups, including patients achieving complete or partial response to chemotherapy, those with liver or lung metastases, left- and right-sided primary tumors, and both RAS wild-type and mutant disease. Importantly, the benefit of R0 resection was maintained irrespective of anti-EGFR– or anti-VEGF–based first-line therapy. Conclusions: R0 resection following systemic chemotherapy is strongly associated with durable survival benefits in patients with initially unresectable mCRC across diverse clinical settings. These findings support the pivotal role of conversion strategies and highlight the importance of multidisciplinary evaluation to identify appropriate candidates for curative-intent resection.
Sociodemographic factors and delays in care for gestational trophoblastic neoplasia.
e17617 Background: Delays in care are associated with worse outcomes for patients with the most common gynecologic cancers, however, there is a paucity of research about health care access and gestational trophoblastic neoplasia (GTN) outcomes. Methods: This was a retrospective cohort study at a single academic institution of patients with gestational trophoblastic neoplasia diagnosed between 2000-2025. Aspects of care and management of GTN were compared across racial, ethnic, insurance, and geographic cohorts. Continuous data were summarized using median and interquartile range, and comparisons between groups were made using Wilcoxon rank sum, Kruskal Wallis, or chi-square tests. Results: 71 patients were included in the study cohort. Patients with Medicaid, Medicare, or insurance assistance/TriCare were more likely to present to the ED as their site of first contact for GTN care (p=0.02). Non-white patients had a longer duration between first concern for GTN and initiation of GTN treatment (31 vs 13 days, p=0.01), however, Hispanic patients had fewer days between first contact with the health care system to initiation of GTN treatment (30 vs 55 days, p-0.04) and first imaging/labs concerning for GTN to treatment (10 vs 21 days, p=0.04). There were no differences in GTN care and management when comparing local to distant county of origin. Conclusions: Our findings suggest that disparities in access to care for GTN may exist for non-white patients and patients with Medicaid, Medicare, or insurance assistance/TriCare. Hispanic patients in this study moved more quickly through the health system to initiate GTN treatment. Given the importance of timely initiation of treatment for GTN to optimize cancer outcomes, interventions are needed to ensure that timely treatment of GTN is accessible to all patients. Characteristics of access to GTN care by race. Race Non-White(N=25) White(N=34) Total(N=59) P-value First Contact Location, n (%) 0.4743 1 OB Clinic 5 (25.0%) 10 (41.7%) 15 (34.1%) PCP clinic 3 (15.0%) 3 (12.5%) 6 (13.6%) ED 12 (60.0%) 10 (41.7%) 22 (50.0%) Other 0 (0.0%) 1 (4.2%) 1 (2.3%) Missing 5 10 15 Number of days from first labs/imaging concerning for GTN to treatment 0.0110 2 N 25 34 59 Median (IQR) 31.0 (15.0, 48.0) 13.0 (8.0, 28.0) 21.0 (9.0, 35.0) 1 Chi-Square p-value; 2 Wilcoxon rank sum p-value.
Lattice SFRT combined with systemic therapy for bulky unresectable hepatocellular carcinoma: A retrospective study on safety and efficacy.
e16270 Background: Lattice spatially fractionated radiotherapy (Lattice SFRT) creates highly heterogeneous “peak-and-valley” dose distributions within tumors, offering a novel approach for bulky hepatocellular carcinoma (HCC) where conventional radiotherapy is often limited. This study retrospectively evaluated the safety and preliminary efficacy of Lattice SFRT combined with concurrent systemic therapy in patients with bulky, unresectable HCC. Methods: Patients with bulky, unresectable HCC who received Lattice SFRT between March 1, 2023, and July 31, 2025, were retrospectively enrolled. All treatments were delivered at a frequency of five fractions per week consecutively. Using volumetric modulated arc therapy (VMAT), the prescribed doses were set as follows: the lattice vertices within the gross tumor volume (GTV) received 35 Gy in 5 fractions, while the entire GTV simultaneously received a lower dose of 10 Gy in 5 fractions, thus constructing a specific intratumoral dose distribution. The treatment regimen was individualized, with 10 patients receiving 2 courses and 3 patients receiving 3 courses of Lattice SFRT. The primary endpoints were objective response rate (ORR) and the incidence of treatment-related adverse events (TRAEs). Secondary endpoints included local control (LC), progression-free survival (PFS), and overall survival (OS). Results: A total of 32 patients were analyzed, of whom 71.9% (n = 23) had tumors with a maximum diameter ≥10 cm. All patients received Lattice SFRT combined with concurrent systemic therapy. After a median follow-up of 9.1 months, the ORR was 53.1%, and local control was maintained in all irradiated lesions. No significant differences were observed in LC (median 11.1 vs. 7.7 months, P = 0.537) or PFS (median 11.1 vs. 7.7 months, P = 0.268) between responders and non-responders. However, responders achieved a significantly longer OS (median not reached vs. 12.3 months, P = 0.005). No grade ≥3 treatment-related hepatic toxicity or unmanageable TRAEs occurred. Hepatic functional reserve remained stable overall after treatment, with improvement in Child-Pugh class observed in four patients (12.5%). Conclusions: For patients with bulky, unresectable HCC, an individualized, multi-course Lattice SFRT regimen employing a “whole-tumor low-dose (10 Gy/5 fx) combined with intratumoral vertex high-dose (35 Gy/5 fx)” strategy demonstrated favorable local control and survival benefit with an acceptable safety profile. These findings support its potential as a promising locoregional treatment option for this challenging patient population, warranting further validation in prospective studies.
Implementation and longitudinal capture of routine patient-reported outcomes in non–small cell lung cancer care at a JCI-certified center in Colombia (2022–2025).
e20105 Background: Routine patient-reported outcomes (PROs) support symptom monitoring and quality benchmarking, yet implementation data from Latin America are limited. We evaluated reach, longitudinal capture, attrition, and PRO score trajectories in a telephone-based program embedded within a non–small cell lung cancer (NSCLC) clinical care pathway at a Joint Commission International (JCI)–certified center since 2023. Methods: Retrospective cohort of eligible NSCLC patients treated at Fundación Santa Fe de Bogotá (July 2022–December 2025). PROs were scheduled at baseline, 6, and 12 months (predefined windows). Instruments included EORTC QLQ-C30 global quality of life (QoL) and dyspnea scales, GAD-7, and PHQ-9. Capture was a recorded score among due evaluations; non-capture was attributed to death or inability to contact after ≥6 attempts within the window. Data quality procedures ensured completeness of recorded scores and harmonized death status across instruments. Results: Of 105 eligible patients, 81 (77.1%) completed at least one PRO; 63.0% were female, 45.7% had stage III–IV disease, and 74.1% were treated with curative intent (ECOG missing 4.9%). Baseline capture ranged from 56.8% to 85.2% across instruments (Table). Capture declined over time, driven predominantly by inability to contact. At 6 months (due = 73), QoL/dyspnea capture was 39/73 (53.4%), with death 3/73 (4.1%) and inability to contact 31/73 (42.5%). At 12 months (due = 58), QoL/dyspnea capture was 28/58 (48.3%), with death 6/58 (10.3%) and inability to contact 24/58 (41.4%). After death harmonization, 12-month GAD-7/PHQ-9 capture was 18/58 (31.0%) with death 6/58 (10.3%) and inability to contact 34/58 (58.6%). Among paired assessments (n = 23), median QoL increased from 75 (IQR 62.5–83.3) at baseline to 83.3 (75–95.8) at 12 months (p = 0.015); median dyspnea remained 0. Median GAD-7 decreased from 2 (0–3) to 0.5 (0–1) and PHQ-9 from 2 (0–4) to 1 (0–1). Lower baseline QoL was associated with larger QoL improvement (p = 0.050), consistent with ceiling effects and survivorship bias. In exploratory models, systemic therapy was associated with lower 6-month inability to contact (odds ratio 0.25, 95% confidence interval 0.07–0.93). Conclusions: Telephone-based PRO collection achieved strong reach and baseline capture in routine NSCLC care, but sustained longitudinal capture was limited primarily by inability to contact. Instrument-specific denominators and harmonized death classification are essential for interpretable benchmarking; hybrid clinic-based and digital workflows may be required for durable longitudinal PRO monitoring in real-world settings.
Racial disparities in endometrial cancer (EC) survival after molecular classification (MC).
5620 Background: Black (BAA) patients with EC have double the mortality rate compared to White patients. It is unclear if these survival differences persist after MC. Here, we examine racial disparities in this context and seek to identify molecular differences by race. Methods: EC samples (n = 10,162: BAA n=2,410, White n=7,752) were analyzed by NGS (NextSeq/NovaSeq) and RNA (NovaSeq) (Caris Life Sciences, Phx, AZ). Four well-described EC groups were created: POLE ultramutated (POLE-mt), MSI-H, TP53-mt, or No Specific Molecular Profile (NSMP; TP53-wt). Overall survival (OS) was obtained from insurance claims and calculated from tissue collection to last contact for MC cohorts. Hazard ratio (HR) was calculated by Cox proportional hazards, with p-value calculated by log-rank test. Race was self-reported. Results: There was a higher prevalence of BAA patients in the TP53-mt subtype (69.1% vs. 43%), compared with POLE-mt (1% vs. 2.26%) and NSMP (16.4% vs. 31%) (p<0.001). Across EC, BAA patients had shorter OS (29.8 vs 39.7 months (m); HR: 1.30 (1.22-1.39), p<0.001). BAA patients had worse OS in the NSMP cohort (36.8 vs 49.5m; HR 1.35 (1.15-1.59), p<0.001) and TP53-mt cohort (26.1 vs 29.6 m; HR 1.13 (1.05-1.22), p=0.002). Race was not associated with differences in OS in POLE-mt (NR vs was 51.4 m) and MSI-H (44.4 vs 45.9 m). There were molecular differences between race when stratified by MC (q<0.05) (Table 1). Gene set enrichment analysis showed downregulation of immune-related pathways in BAA. In NSMP tumors, BAA patients had lower IFNγ signature (0.72-fc) and worse post-pembrolizumab survival (16.9 vs 24.6 m; HR 1.46 (1.09-1.95), p=0.011). Conclusions: Previous studies demonstrated that racial disparities in endometrial cancer persist even when controlling for histology. This study demonstrates that these disparities persist even after controlling for MC, as defined by the ProMisE classification. BAA patients were more likely to develop TP53-mt tumors, but the survival disparity was largest in the NSMP group. Furthermore, Black and White patients exhibit differential expression of known prognostic mutations even within the same MC group. Molecular differences by race and subtype. Biomarker TP53-mt NSMP BAA % White % BAA % White % ARID1A -mt 4.47 10.3 32.8 48.9 CTNNB1 -mt NS NS 31.1 40.2 FGFR2 -mt 0.60 2.94 3.29 11.3 PIK3CA -mt 23.1 36.6 NS NS PIK3R1 -mt 9.58 15.4 17.9 35.0 PTEN -mt 6.83 15.7 40.4 66.9 PPP2R1A-mt 15.5 23.8 NS NS CDKN2A -del NS NS 22.0 13.7 CDKN2B -del NS NS 13.7 5.45 MTAP -del NS NS 18.8 8.92 ER+ NS NS 62.6 76.0 PR+ NS NS 53.1 67.4 NS=not significant.
Monalizumab plus durvalumab plus platinum-based chemotherapy for first-line treatment of extensive stage small-cell lung cancer: Early efficacy results from MOZART trial.
8098 Background: Extensive stage small cell lung cancer (ES-SCLC) is an area of unmet need where novel treatment strategies are urgently needed. Preclinical data in SCLC demonstrate higher expression of NKG2A, an immune checkpoint expressed on natural killer (NK) cells and CD8+ T cells, with consequent reduced NK cell mediated anti-tumor activity, substantially enhanced metastatic dissemination of tumor cells, and amelioration of metastasis with hyperactivation of NK cells. We hypothesized that NKG2A inhibitor monalizumab (M) may enhance the efficacy of first-line therapy in ES-SCLC by promoting both NK and CD8+ T cell functions. Methods: We conducted a single arm, multicenter, investigator-initiated phase II study with a safety lead-in cohort, evaluating M in combination with platinum (P), etoposide (E), and durvalumab (D) in patients (pts) with previously untreated ES-SCLC. One prior cycle of EP ± D was allowed. Pts received EP + D + M every 3 weeks for 4 cycles followed by D + M every 4 weeks until disease progression or unacceptable toxicity. Primary endpoints were 1-year (yr) progression-free survival (PFS) and safety. Secondary endpoints were objective response rate (ORR), 1-year overall survival (OS) and intracranial PFS (iPFS). We hypothesize that the combination will lead to improvement in 1-yr PFS to 33% compared to historical control of 18% (1-sided alpha:10%, power: 80%). Results: 30 pts were enrolled (median age:62.5yrs (range, 53-79)). 10pts (33.3%) were female and 6 (20%) were Black. 14pts (46.7%) received one cycle of EP ± D prior to study entry. ORR was 73.3% (complete response = 3, partial response = 19). At median follow-up of 14.2months (mo) (range, 6.4-not estimable (NE)): estimated 1-yr PFS: 20.6%, 18-mo PFS: 15.5%, median (m) PFS: 4.8mo (4.5-5.3), 1-yr OS: 67.4%, mOS: NE (10.2-NE). Most common site of progression was brain with miPFS of 5.3mo (4.8-10.8); 1-yr iPFS: 21.7%, 18-mo iPFS: 16.3%. 4pts had PFS longer than 1yr, 3 of whom had brain metastasis at baseline. No dose limiting toxicities were identified in the safety lead-in cohort. Treatment related AEs (TRAEs) at least possibly related to D and/or M occurring in ≥10% of pts were fatigue (23%), decreased lymphocyte count (13%), hypothyroidism (10%), decreased neutrophil count (10%), and increased lipase (10%). 5 pts (17%) had grade (G) 3/4 TRAEs: decreased neutrophil count (n = 3), encephalitis (n = 1), acute kidney injury (n = 1). Toxicities solely attributed to M were all G 1: increased lipase (n = 2), headache (n = 1), and increased amylase (n = 1). Conclusions: Addition of M to first-line EP + D led to no new severe AEs in patients with ES-SCLC. Estimated 1-yr PFS was not statistically superior to historical control with EP +D, yet a subset of patients including those with baseline brain metastasis derived durable benefit. Long term follow-up and biomarker analysis are ongoing. Clinical trial information: NCT05903092 .
The effect of short stories on secondary school students’ reading comprehension skills and attitudes in Northwest Ethiopia
Background Reading comprehension is a critical skill for English as a foreign language learner. However, many Ethiopian secondary school students have been having trouble in reading comprehension, where English is a medium of instruction. Therefore, this study examined the impact of short stories on secondary school students’ reading comprehension and assessed their attitude towards short stories. Methods A quasi-experimental design was employed. The participants were two sections of 9 th graders (n = 120) that were randomly assigned to experimental (n = 60), and control (n = 60) groups. The data were collected through a pre-and post-intervention reading comprehension test and an interview. Quantitative data were analyzed using independent and paired samples t-tests with effect sizes reported to strengthen statistical interpretation. Qualitative data were collected through interview with seven experimental group participants and analyzed thematically. Results Results showed no significant difference between groups at pretest in their reading comprehension skills (t = 0.32, df = 118, p = 0.75). The post-test results showed that the experimental group (m = 10.38, sd = 2.63) significantly outperformed the control group (m = 6.72, sd = 2.57, p = 0.001). Within- groups analysis confirmed that the control group showed no significant change (p = 0.57). However, the experimental group showed significant change in reading comprehension test performance (p = 0.01). Interview findings displayed that short stories improved reading comprehension skills and fostered a positive attitude toward reading. Conclusion The integration of short stories into English foreign language reading instruction significantly enhanced students’ reading comprehension skills. It also increased students’ positive attitudes in the reading texts. Therefore, it is recommended that English foreign language teachers should supplement reading skills instruction with culturally relevant short stories, and curriculum developers should incorporate more short stories in grade nine English textbooks to develop students’ reading comprehension skills.
Interfused Graphene Fiber Membranes Enable Volumetric Electron‐Transfer Advanced Oxidation via Interlayer Site Activation
ABSTRACT Electron‐transfer‐involved persulfate‐based advanced oxidation processes (ET‐AOPs) are attractive for wastewater treatment because of their high selectivity and environmental robustness. However, ET‐AOPs are intrinsically dual‐site reaction requiring efficient electron transfer between persulfate‐binding and pollutant‐binding sites. This constraint is often obscured in powder catalysts but becomes critical when reactions in integrated catalytic membranes or devices, where spatial separation of active sites and discontinuous conductive pathways can electronically isolate internal regions, substantially limiting reaction site utilization. Here we report an interfused nitrogen‐doped reduced graphene oxide fiber (N‐rGOF) membrane that overcomes this by unifying long‐range electronic continuity with internal site accessibility. Fused junctions between fibers form a continuous, low resistance conductive network, while the layered rGO structure enables persulfate entry into interlayers to activate otherwise inaccessible internal nitrogen sites through an interlayer entry‐induced site activation (IESA) mechanism. The N‐rGOF membrane degraded bisphenol A (BPA) ∼5.2 times faster than a noninterfused counterpart and maintained excellent removal of trace organic pollutants in real livestock wastewater with high ionic strength and organic loading. Furthermore, the intrinsic potential difference generated during catalysis enables a floatable, self‐powered setup that couples pollutant degradation with real‐time electrical signaling, illustrating the conceptional feasibility of integrated monitoring and remediation based on one single system.
Enhancing Superlubricity and Wear Resistance in Mechanically Robust Hydrogel via Microliter‐Scale Subsurface‐Initiated Polymer Brush Grafting
ABSTRACT Hydrogels represent an ideal for articular cartilage replacement, with hydrogel‐polymer brush layered composites emerging as a promising strategy to simultaneously achieve ultra‐low friction and high load‐bearing capacity. However, current approaches for grafting polymer brushes from hydrogels usually require oxygen‐free conditions, large volumes of polymerization solutions, and excessive monomer consumption. Herein, we developed a facile, oxygen‐tolerant subsurface‐initiated polymer brush grafting strategy to fabricate cartilage‐mimicking layered hydrogel‐polymer brush materials, using only microliter volume of monomer solution. To validate this, a mechanically robust, physically cross‐linked poly(vinyl alcohol)‐based hydrogel with subsurface‐initiated polymerization activity was designed by incorporating a tannic acid‐derived cross‐linkable atom transfer radical polymerization (ATRP) initiator, which serves as a robust load‐bearing substrate. Subsequently, polymer brushes were grafted from the subsurface of this robust hydrogel matrix with microliter solutions, yielding cartilage‐mimicking layered structure with an interpenetrated polymer brush‐hydrogel composite lubricating phase. Notably, the resulting materials exhibited synergistic superior lubrication, high load‐bearing capacity, and excellent wear resistance, achieving a stable and ultra‐low friction coefficient (COF∼0.017) over 80,000 cycles under 10 N load. This strategy greatly lowers technical barriers to the fabrication of hydrogel‐polymer brush materials and further advances their practical applications in the field of articular cartilage repair and artificial joint replacement.
Advancing Repaglinide delivery: Development and evaluation of optimized liposomal systems
Hybrid Interface Engineering With Piperidinium Ionic Polymers Toward 21% Efficiency of Organic Solar Cells
ABSTRACT The cathode interlayer (CIL) serves as a critical interfacial component that governs the performance of organic solar cells (OSCs) by directly modulating electrode conductivity, interfacial dipole, and work function. However, the widespread use of perylene‐diimide‐based CILs is constrained by their intrinsic limitations in finite conductivity and poor thickness tolerance. To address this issue, we propose a hybridization strategy by incorporating a piperidinium ionic polymer (PIP) into PDINN. The bulkiness of the ionization piperidinium group modulates the film‐formation kinetics of hybrid CIL and endows additional electrostatic forces to promote tighter molecular packing of PDINN. Furthermore, the strong interfacial dipole introduced by piperidinium ionization collectively contributes to optimized film morphology, reduced cathode work function, and increased conductivity, resulting in superior CIL thickness insensitivity and markedly enhanced OSC performance. Notably, employing the PDINN:PIP hybrid CIL in PM6:D18:L8‐BO‐based devices yields a remarkable PCE of 20.85%, showing a pronounced improvement compared to the control device with individual PDINN as CIL (19.80%). This approach also demonstrated broad applicability, yielding excellent performance in multiple active‐layer systems. Overall, this research underscores the effectiveness of piperidinium ionization on hybrid CILs to fully exploit their potential in OSCs.