Browse Articles
Discover research articles across all indexed journals
Radiation for oligoprogression to prolong systemic therapy: Experience from early drug development trials.
e15102 Background: For patients with metastatic cancer treated on an early-phase clinical trial, disease progression typically prompts discontinuation of study drug and initiation of an alternative systemic therapy and/or supportive care. Emerging data suggests local therapies may provide clinical benefit when disease spread is limited (oligometastatic), potentially due to eradication of emergent resistant subclones of disease. Evidence in patients treated on early-phase investigational trials is limited. In this study, we test the hypothesis that radiation to oligoprogressive lesions (≤ 5 sites) can prolong potential benefit from systemic therapy and allow patients to remain on trial longer. Methods: We retrospectively reviewed patients on early-phase oncology trials within the Early Drug Development Service at Memorial Sloan Kettering Cancer Center between October 2009 to November 2023. Imaging and radiation records were reviewed to categorize patients into those who received metastasis-directed radiation therapy (RT) to all sites of oligoprogressive disease versus those receiving palliative RT only to selected lesions with other progressing disease left untreated. Kaplan-Meier methods were used to estimate time on trial (time from RT start to protocol treatment discontinuation), and log-rank test compared duration between groups. Results: Of 139 patients who received radiation for extracranial metastatic disease, 43% (60 patients) underwent palliative RT with additional sites of progression left untreated, 56% (78 patients) underwent metastasis-directed RT to all sites of progressive disease, and 1 patient underwent RT on 2 separate trials. 6% of patients (8/139) were identified with grade 4/5 toxicity, none of which were related to RT. 3 events preceded RT delivery and others were due to untreated disease progression. Median time from start of RT to discontinuation of study treatment was 41 days (95% CI: 29-63, range 3-582) for patients undergoing palliative RT with additional sites of progression left untreated, and was significantly longer, 141 days (95% CI: 106-213, range 7-2164), for patients receiving metastasis-directed RT to all sites of progression (p < 0.0001). Conclusions: In a large, single-center, early-phase trial experience, patients treated with metastasis-directed radiation to all sites of oligoprogression experienced extended time on trial, which was significantly longer compared to palliative RT leaving progressing disease untreated, with some patients benefiting for additional years. No serious adverse events related to RT occurred. These retrospective findings warrant further validation, as patient selection factors could influence outcomes. Metastatic ablation for progressing disease is a potentially powerful tool to extend the benefit of systemic therapy, and should be considered in trial design, even in the setting of exploring novel agents.
Outcomes of PD-(L)1 inhibitor continuation or rechallenge after first-line progression in recurrent or metastatic head and neck squamous cell carcinoma.
6059 Background: PD-(L)1 inhibitors are a standard first-line (1L) backbone for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, many patients progress after 1L PD-(L)1–based therapy, and optimal post-progression strategies remain undefined. In particular, the benefit of continuing or rechallenging PD-(L)1 inhibitors beyond progression is unclear. Methods: In this multicenter retrospective study, we included patients diagnosed with R/M HNSCC (oral cavity, oropharynx, larynx, and hypopharynx) between 2016 and May 2025 at Samsung Medical Center and Mass General Brigham. Eligible patients received 1L PD-(L)1–containing regimen, experienced disease progression, and underwent subsequent second-line systemic therapy. Patients were categorized by post-progression strategy: continuation or rechallenge with PD-(L)1 inhibitors versus non–PD-(L)1–based therapy. Overall survival (OS) was defined as the time from initiation of 1L therapy to death from any cause. Results: A total of 252 patients with R/M HNSCC met eligibility criteria. Median age was 64; 191 (76%) were male; 68 (27.0%) were HPV-positive; and 217 (86%) were PD-L1 positive (CPS ≥1). Twenty-six patients (10.3%) received anti-PD-(L)1 monotherapy, and 84 (33%) remained on 1L therapy for ≥6 months. Median OS for the entire cohort was 18 months (95% CI, 15.9-20.1). Median OS was 21.1 months among patients who continued or were rechallenged with PD-(L)1 inhibitor (n = 112) versus 14.4 months in those who were not (n = 140) (p < 0.001). On multivariable analysis including post-progression PD-(L)1 continuation/rechallenge, HPV status, PD-L1 expression, age, sex, ECOG performance status, and duration of 1L PD-(L)1 therapy, continuation or rechallenge with PD-(L)1 inhibitors (HR 0.583, p=0.003) and 1L PD-(L)1 duration ≥6 months (HR 0.487, p<0.001) were independently associated with improved OS. Conclusions: In this study, continuation or rechallenge with PD-(L)1 inhibitors after progression on 1L therapy was associated with improved OS in patients with R/M HNSCC, independent of PD-L1 expression or HPV status. Prolonged benefit from 1L PD-(L)1 therapy was also independently associated with favorable survival. These findings suggest that selected patients may derive continued clinical benefit from anti-PD-(L)1–based strategies beyond progression and support prospective studies to refine patient selection and optimize post-progression treatment strategies.
Inhalable polyphenolic-based nanoparticles for localized lung cancer treatment.
e20758 Background: Lung cancer remains a leading cause of cancer-related morbidity and mortality worldwide. Although conventional chemotherapy is a mainstay of treatment, its clinical utility is often limited by systemic toxicity, poor bioavailability at the tumor site, and off-target effects. Inhalation-based drug delivery using nanocarriers has emerged as a promising strategy to achieve localized lung targeting, bypass first-pass metabolism, and enhance therapeutic efficacy while minimizing systemic exposure. In this study, we report a facile inhalable, tannic acid–based nanoparticles (GA@TANPs) as a polyphenolic nanoplatform for localized lung cancer therapy. Methods: Gambogic acid (GA)–loaded CTA nanoparticles (GA@TANPs) were synthesized via a cross-linking approach and comprehensively characterized for physicochemical properties, including particle size, morphology, thermal behavior, chemical composition, and drug-loading efficiency using DLS, FT-IR, DSC, SEM/TEM, and TGA. Cellular uptake and intracellular trafficking were evaluated in A549 and NCI-H1299 lung cancer cells using fluorescence microscopy and flow cytometry. The therapeutic potential of GA@TANPs was assessed through in vitro cytotoxicity (CCK-8), mucoadhesion, mucopenetration, Boyden chamber migration, spheroid penetration, and apoptosis assays. Results: The optimized GA@TANPs exhibited a spherical morphology with a mean particle size below 200 nm and a mildly negative surface charge (−7.1 ± 0.5 mV), suitable for deep lung deposition. The nanoparticles demonstrated sustained drug release, enhanced mucus penetration, and improved tumor spheroid infiltration, closely mimicking in vivo tumor conditions. Cellular uptake studies confirmed significantly higher intracellular accumulation of GA@TANPs compared to free GA, with evidence of efficient endosomal escape. Functionally, GA@TANPs showed superior anticancer activity, including reduced cell viability, inhibited migration, and increased apoptosis in both lung cancer cell lines. Conclusions: These findings highlight the potential of nebulization-based inhalable GA@TANPs formulations as an effective localized drug delivery system for lung cancer therapy.
First-in-human study of DM002, an anti-MUC1/HER3 bispecific antibody-drug conjugate, in patients with advanced solid tumors.
3037 Background: DM002 is a bispecific ADC (BsADC) conjugated to BLD1102, a linker/payload system composed of a linker and a DNA topoisomerase I inhibitor (BCPT02), targeting MUC1 and HER3 with an average DAR value of 8. MUC1 and HER3 are highly co-expressed in several types of solid tumors, for which DM002 has demonstrated robust anti-tumor activity in PDX/CDX models. Methods: This is a First-in-human dose-escalation study (NCT06751329). Patients (pts) with advanced solid tumors received DM002 by IV administration from 1 to 6.0 mg/kg Q3W. The classical “3+3” design was utilized to evaluate safety, tolerability and preliminary efficacy. Tumor response was evaluated by the Investigators based on RECIST v 1.1. A Safety Monitoring Committee (SMC) was established to determine the dose levels, dose regimen, and the maximum tolerated dose (MTD)/ recommended dose for expansion (RDE). Results: As of 28 Dec 2025, a total of 29 pts from China, United states of America and Australia were enrolled and received ≥1 dose of DM002 across 5 dose cohorts. Median age was 61 years (range 45-80). Baseline ECOG scores were 0 (n=8), 1 (n=21) with all pts progressed after an average of 2.5 (range 1-5) prior lines of available standard therapy. There were three dose-limiting toxicities observed in 2 patients at 6.0 mg/kg. The MTD is 4.5mg/kg. Nineteen pts (65.5%) experienced treatment-related adverse events (TRAEs), mainly manifested as hematological toxicity and gastrointestinal reactions. the most common TRAEs (≥15%) including: nausea (37.9%), neutropenia (37.9%), thrombocytopenia (34.5%), anemia (31%), vomiting (27.6%), leukopenia (20.7%), hyponatremia (20.7%), diarrhea (17.2%), alanine aminotransferase increased (17.2%), hypoalbuminemia (17.2%). Most TRAEs were Grade 1-2 and Grade ≥3 TRAEs reported in 12 pts (9 neutropenia, 5 leukopenia, 4 thrombocytopenia, 3 anemia, 2 lymphocytopenia, hyponatremia and febrile neutropenia, 1 aspartate aminotransferase increased, blood bilirubin increased, monocyte count decreased, myelosuppression, hypocalcemia, malaise and infection). No ILD was observed. Among 15 pts having imaging tumor assessment by RECIST v1.1, there were 3 PRs, including 1 pt with prostate cancer and 1pt with ovarian cancer at 3.0 mg/kg, and 1 pt with pancreatic cancer at 4.5 mg/kg, and 8 pts with stable disease (SD). In the 3.0/4.5/6.0 mg/kg dose groups, a total of 8 pancreatic pts underwent imaging tumor assessment, with 1 pt achieving PR, and 5 pts achieving stable disease (SD). Conclusions: DM002 is safe and tolerable up to 4.5 mg/kg dose level. In pancreatic cancer, prostate cancer and ovarian cancer, DM002 has demonstrated an encouraging efficacy with a manageable safety profile. The putative RDEs are 3.0 and 3.5 mg/kg which will be further evaluated in phase II trials. Clinical trial information: NCT06751329 .
Clinical efficacy and safety of BM201 intra-tumoral injection and radiotherapy in advanced solid tumors: Results from the phase I/IIT study.
2599 Background: For vaccine design, an antigen and an adjuvant are necessary for an effective immune response. In the context of therapeutic tumor vaccination, in situ vaccination has garnered increasing attention as it enables tumors to provide antigens through radiotherapy or intra-tumoral (i.t.) delivery of immunomodulators. BM201, a selective TLR7/8 agonist uniquely designed for intra-tumoral (i.t.) administration, aims to effectively activate antigen-presenting cells and enhance immunogenicity through combination with radiotherapy by more effectively presenting the tumor antigens exposed to T cells. When combined with intravenous (i.v.) infusion of αPD-1 monoclonal antibody (mAb), it relieves tumor immunosuppression and exerts synergistic anti-tumor effects. Methods: This is an open-label, exploratory, and phase I/IIT study. Phase I portion was a dose-escalation study designed to investigate BM201 (dose range: 24-240mg, i.t. every 2 weeks) in combination with hypofractionated radiotherapy (5-8Gy, 4 fractions) (R-ISV-BM201) in patients with refractory or metastatic solid tumors. Phase IIT portion was designed to investigate BM201 (dose range: 24-240mg, i.t. every 3 weeks) in combination with hypofractionated radiotherapy (5-8Gy, 4 fractions) plus αPD-1 (200mg, i.v. every 3 weeks) (R-ISV-BM201 + αPD-1) in patients with refractory or metastatic soft tissue sarcomas. Primary objective of both 2 studies was safety and tolerability. Secondary endpoints included PK and preliminary anti-tumor activity according to RECIST 1.1 in Phase I, while anti-tumor activity according to irRECIST 1.1 in Phase IIT. Results: Till December 05, 2025, 29 patients had been treated with BM201 (19/29 in Phase I, 10/29 in Phase IIT). Among the 29 patients, 51.7% had been unresponsive to immunotherapy (prior αPD-1). Plasma exposure increased with dose. A sustained-release PK characteristic was observed in most patients experiencing tumor shrinkage. Abscopal effects were observed in 31.6% (6/19) and 50% (5/10) of patients in Phase I and Phase IIT, respectively. In Phase I, the objective response rate (ORR) was 5.2%, and the disease control rate (DCR) was 84.2%; while these were 10.5% and 84.2% in injected lesions. In Phase IIT, the ORR was 20%, and the DCR was 100.0%; while these were 46.1% and 92.3% in injected lesions. The median progression-free survival was 7.7 months, the median overall survival was 17.0 months, and the median duration of response in injected lesions was 5.6 months. The majority of TRAEs were grade 1-2. Grade 3-4 TRAEs mainly included lymphocytopenia, anemia, thrombocytopenia, and hypertension. No grade 5 TRAEs or dose-limiting toxicity was observed. Conclusions: R-ISV-BM201 has a manageable safety profile and has shown encouraging anti-tumor activity. A trigger systemic immune response would be expected when it is synergized with αPD-1 mAb. Clinical trial information: Phase I: NCT06368960 ; Phase IIT: ChiCTR2300077953.
Incidence of cardiac-related deaths (CRDs) among patients (pts) aged ≥ 65 years with B-cell malignancies (BCMs) treated with ibrutinib (ibr).
e19020 Background: Ibr is associated with increased risk of fatal cardiac failure in clinical trials; however, real-world (RW) ibr cardiovascular safety data are limited. We assessed RW incidence of CRD in Medicare beneficiaries with BCM receiving ibr. Methods: This retrospective study used the deidentified Medicare Fee-for-Service (FFS) database. Pts were included if they initiated ibr between 2017-2021 (National Death Index [NDI] data cutoff), had ≥2 nondrug claims ≥1 day apart for the same qualifying BCM and had ≥12 mo of continuous Medicare enrollment prior to index date of ibr initiation. Pts were followed until earliest of ibr discontinuation, death, end of enrollment/study. Baseline characteristics were summarized using descriptive statistics overall and by BCM group (CLL/SLL, single non-CLL BCM, multiple BCMs). CRD was defined as diagnosis codes for cardiac arrest/sudden cardiac death (CA), atrial fibrillation/flutter (AF), heart failure (HF), myocardial infarction, ventricular fibrillation/flutter, ventricular tachycardia, sudden death, or ischemic stroke listed as cause of death in NDI. Number and proportion of events were summarized. Incidence rate (IR) was estimated as number of events per 1000 person-years (pys) on ibr. Cumulative incidence was estimated at key times, with death from other causes as a competing risk. Age- and sex-adjusted CRD IR was also estimated among general FFS beneficiaries in 2021. Results: Of 13,241 pts, 10,499 had CLL/SLL, 2,622 had non-CLL BCM, 170 had multiple BCMs. Median age at index was 77.2 years (IQR, 72.2-82.8). Most were male (57.7%) and non-Hispanic White (90.7%). Median baseline NCI comorbidity index was 0.29 (IQR, 0-0.74); most common comorbidities were hypertension (73.6%) and hyperlipidemia (69.2%). A total of 568 (4.3%) CRDs were identified with an overall IR of 35.2 per 1000 pys (Table). Most CRDs were CA (n=243), HF (n=190), or AF (n=148). Median ibr treatment duration was 268 days (IQR, 119-659). In pts with CLL/SLL, median follow-up was 298 days (IQR, 120-718) with most CRDs of CA (n=189; 1.8%), HF (n=147; 1.4%), AF (n=112; 1.1%). Among >16 million general Medicare beneficiaries in 2021, adjusted CRD incidence was 2.1% with an IR of 19.1 per 1000 pys. Conclusions: In this large RW cohort of pts aged ≥65 years with BCM treated with ibr, the incidence of 35.2 CRDs per 1000 pys on ibr was higher than that observed in the general Medicare population of similar age and sex distribution. Most events occurred in first 6 mo of treatment, with cumulative incidence increasing over the duration of ibr exposure. During Ibr treatment Overall CLL/SLL Non-CLL BCM CRD events, n (%) 568 (4.3) 438 (4.2) >120 (>4.5) CRD IR per 1000 pys (95% CI) 35.2 (32.4-38.2) 32.3 (29.3-35.5) 50.6 (42-60.4) Time to event in pts with CRD, median (IQR), days 146.5 (60.5-423.5) 153 (65-456) 135 (47-300) Cumulative CRD probability, %Day 180Day 365 2.73.8 2.63.5 3.34.9
Longitudinal on-treatment plasma microRNA profiling for identification of biomarker signatures associated with gemcitabine/nab-paclitaxel therapy in pancreatic ductal adenocarcinoma.
e16387 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor outcomes and limited benefit from systemic therapy. Non-invasive biomarkers capable of dynamically capturing treatment response are needed to improve therapeutic monitoring. Circulating plasma microRNAs (miRNAs) represent a promising class of longitudinal biomarkers. We evaluated on-treatment changes in plasma miRNA profiles in PDAC patients receiving gemcitabine plus nab-paclitaxel (GnP). Methods: Patients with histologically confirmed PDAC were enrolled in a prospective clinical study of GnP. Plasma samples were collected longitudinally at baseline and during treatment. Total RNA was isolated from plasma and subjected to miRNA sequencing, with differential expression analysis performed between pre- and on-treatment samples. Selected miRNAs were validated by RT-qPCR. Exploratory functional studies were conducted in PDAC cell lines. Results: Twenty-eight patients were enrolled, 13 of them had a paired microRNA blood samples (before and on treatment) to be evaluable for longitudinal biomarker analyses. Longitudinal plasma miRNA profiling revealed reproducible on-treatment modulation of circulating miRNAs, including upregulation of miR-296-3p, miR-127-3p, miR-766-5p, miR-202-3p, miR-449c-5p, miR-993, and miR-625-3p, and downregulation of miR-15b-5p, miR-3150a, miR-3158-3p, and miR-4669, which were confirmed by RT-qPCR. The forced expression of miR-3158-3p inhibited cell growth and increased the drug sensitivity to GnP in MiaPaCa2 cells. Correlation of selected miRNAs with therapeutic response and resistance is ongoing using gain- and loss-of-function approaches with miRNA mimics and inhibitors in PDAC models. The correlation of clinical outcomes with the microRNA panel changes is ongoing. Conclusions: Longitudinal on-treatment plasma miRNA profiling identifies dynamic biomarker signatures associated with GnP therapy in PDAC. These circulating miRNAs may serve as minimally invasive biomarkers for treatment monitoring and provide biologic insight into therapy-associated tumor responses. Continued enrollment and longitudinal follow-up are ongoing to further assess clinical relevance.
Efficacy and safety of darolutamide plus androgen deprivation therapy in de novo metastatic hormone-sensitive prostate cancer: A single-center retrospective study.
e17085 Background: ADT alone provides limited benefit in mHSPC, with most patients progressing to castration resistance. Darolutamide combined with ADT is a promising non-chemotherapy option. Real-world data in Chinese patients remain scarce. This study aimed to evaluate the efficacy and safety of darolutamide plus ADT in a real-world mHSPC cohort. Methods: This single-center retrospective study included 78 de novo mHSPC patients treated at Tianjin Cancer Hospital, with enrollment between January 29, 2024, and June 11, 2025. Darolutamide was initiated at a reduced dose (half of the full dose) for the first two weeks, and then escalated to the full recommended dose of 600 mg. For ADT treatment, goserelin microspheres, 3.6mg, every 28 days. The primary endpoint was PSA reduction at 6 months; secondary endpoints included PFS, time to CRPC, OS, and AEs. Results: Of the 78 patients, the median age was 71 years, and 91.0% had ECOG 0–1. 51 (65.4%) had a Gleason score (GS) of 6–8, and 27 (34.6%) had a score of 9–10. Visceral metastasis was present in 18 patients (23.1%), and bone metastasis in 47 patients (60.3%), 45 (57.7%) were low-volume and 33 (42.3%) were high-volume. The median baseline PSA was 46.77ng/ml. The median follow-up was 9.9 months (95%CI: 9.4–10.4). At 6 months, 98.7% of patients achieved a PSA reduction of ≥90%, and all had a reduction of ≥50%. PSA decreased to < 0.2 ng/ml in 65 patients (83.3%), with 43 (55.1%) with PSA < 0.02 ng/ml. Across subgroups defined by GS, visceral metastases, and tumor burden, all patients achieved PSA50, indicating consistent clinical benefit. However, the proportion achieving PSA < 0.2 ng/ml differed among subgroups: patients with GS 6–8 showed higher response rates than those with GS 9–10 (P < 0.05), and patients without visceral metastases achieved higher rates than those with visceral metastases (88.3% vs. 66.7%, P < 0.05). No significant difference was observed between high and low tumor burden groups. As of the cut-off date(June 11, 2025), 75 patients (96.2%) remained on treatment. Data for survival endpoints are immature at this time. AEs occurred in 24 patients (30.8%), with the most common being fatigue (11.5%) and hot flashes (10.3%). One patient experienced a grade 3 AE (hypertension), while others had grade 1–2 AEs. No unexpected safety signals were observed, and AEs were manageable. Conclusions: This ongoing single-center, large-sample real-world study suggests that darolutamide plus ADT is an effective and well-tolerated treatment option for Chinese mHSPC patients. Both patients with and without visceral metastases derived clinical benefit, with those without visceral metastases showing more pronounced improvements. Continued follow-up is necessary to assess long-term efficacy and safety.
Impact of symptom burden, psychological distress, and treatment accessibility on quality of life in people with cancer in Syria.
11046 Background: In low-resource and conflict-affected settings, barriers to cancer care may amplify symptom burden and psychological distress, leading to poor quality of life (QoL). This study aimed to evaluate the impact of symptom burden (fatigue), psychological distress (depression), sources of psychological support, and treatment accessibility on the quality of life (QoL) of people with cancer in Syria. Methods: A cross-sectional study was conducted between April and May 2025 at Albairwni Hospital, Syria’national cancer center. Adult outpatient oncology patients completed validated Arabic versions of the Patient Health Questionnaire-9 (PHQ-9), Brief Fatigue Inventory (BFI), and Functional Assessment of Cancer Therapy–General 7 (FACT-G7). Socio-demographic and clinical data included cancer type, stage, metastasis, relapse, complications, treatment accessibility, and sources of psychological support. Statistical analyses included group comparisons and Spearman correlation. Results: Among 225 participants (median age 53; 71.6% female; 65.8% rural). 41.8% reported difficult access to treatment, while only 18.7% reported easy access. Psychosocial support was primarily provided by family (87.1%), followed by religious sources (37.3%) and healthcare providers (18.2%). Breast cancer comprised 49.3% of cases. By PHQ-9, 77.3% had depressive symptoms (mild 26.7%, moderate 25.8%, moderately severe 17.8%, severe 7.1%). Mean BFI total score was 32.5 ± 23.6. Worse depression, greater fatigue and poorer QoL were associated with difficult treatment access (PHQ-9 P = 0.01; BFI P = 0.01; FACT-G7 P = 0.005), advanced stage (PHQ-9 & FACT-G7 P<0.001; BFI P=0.001), presence of metastases (PHQ-9 P = 0.001; BFI P = 0.01; FACT-G7 P < 0.001). Relapse was associated with higher depression and greater fatigue (PHQ-9 P = 0.04; BFI P = 0.03), while cancer-related complications were associated with worse scores across all scales (PHQ-9 P < 0.001; BFI P = 0.001; FACT-G7 P < 0.001). Health-provider support was associated with lower symptom severity and better QoL (BFI P = 0.01; FACT-G7 P = 0.003). Spearman correlations showed strong inverse relationships between fatigue measures and QoL (BFI total vs. FACT-G7 ρ = −0.71, P < 0.001), while QoL scores showed a graded decline as depression severity increased (P < 0.001). Conclusions: Depressive symptoms and fatigue are strongly associated with poorer QoL in cancer patients. Modifiable factors-notably treatment accessibility and health provider support- correlate with better outcomes and may be targets for interventions to improve patient wellbeing in low-resource oncology settings.
Trends in thyroid cancer mortality among adults in the United States and Puerto Rico, 1999–2021.
e18023 Background: Thyroid cancer is a leading endocrine malignancy characterized by rising global incidence. Despite advancements in diagnosis and therapy, it continues to impose a significant public health burden. This study evaluates thyroid cancer mortality trends in the United States and Puerto Rico from 1999 to 2021, stratified by sex, race/ethnicity, and geographic factors. Methods: We analyzed CDC WONDER Multiple Cause-of-Death data to estimate age-adjusted mortality rates (AAMR) for thyroid cancer (ICD-10 Code: C73) among adults. Crude mortality rates (CMRs) and AAMR per 100,000 were calculated. Joinpoint regression was used to estimate annual percentage change (APC) and average annual percentage change (AAPC) with 95% confidence intervals (CIs), stratified by sex, race, ethnicity, and census regions. Results: From 1999 to 2021, 38,642 thyroid cancer-related deaths were reported among adults in the United States and Puerto Rico. Of these, 21,649 (56.0%) were females and 16,993 (44.0%) were males. By race and ethnicity, the highest number of deaths occurred among Non-Hispanic (NH) Whites (29,212; 75.6%), followed by Hispanics (3,745; 9.7%), NH Blacks (3,532; 9.1%), and NH Asians (1,905; 4.9%). The South had the highest number of deaths by Census region (13,192; 34.2%), while the Northeast had the lowest (7,498; 20.0%). Conclusions: Thyroid cancer mortality shows significant rising rates among men, a disproportionately high burden among NH Asian/Pacific Islanders, and notable regional increases in the South and Midwest. These evolving disparities underscore the need for targeted clinical interventions and equitable healthcare access to address sex-specific and geographic inequities in endocrine cancer outcomes. Trends related to thyroid cancer mortality among adults in the United States and Puerto Rico, 1999 to 2021. Variable Deaths (n) AAMR (95% CI) 1999 AAMR (95% CI) 2021 Male 16,993 0.68 (0.63 to 0.75) 0.79 (0.74 to 0.84) Female 21,649 0.70 (0.65 to 0.75) 0.77 (0.73 to 0.82) NH White 29,212 0.67 (0.63 to 0.71) 0.75 (0.72 to 0.79) NH Blacks 3,532 0.69 (0.57 to 0.84) 0.75 (0.64 to 0.86) NH Asians 1,905 0.98 (0.69 to 1.34) 0.87 (0.72 to 1.04) Hispanics 3,745 1.06 (0.85 to 1.31) 0.92 (0.81 to 1.05) Northeast 7,498 0.74 (0.66 to 0.83) 0.60 (0.54 to 0.68) South 13,192 0.64 (0.58 to 0.7) 0.78 (0.72 to 0.84)
Lycopene and survival in patients with stage III colon cancer: Findings from CALGB (Alliance)/SWOG 80702.
3630 Background: Lycopene, a non-provitamin A carotenoid, has been reported to inhibit colon cancer development; however, its prognostic role after colon cancer diagnosis remains unknown. Given emerging evidence suggesting greater intake of lycopene-containing – particularly, tomato-based – foods may improve colon cancer prognosis, we assessed the association of postdiagnosis lycopene consumption with survival among 1666 patients (pts) with stage III colon cancer. Methods: Through an NCI-sponsored multicenter phase III adjuvant chemotherapy trial (CALGB/SWOG 80702; NCT01150045), we examined the consumption of total lycopene (dietary plus supplementation) and dietary lycopene as well as lycopene-containing foods (tomato-based foods plus other lycopene-containing foods) and tomato-based foods via validated food frequency questionnaires (FFQs) collected at 6 weeks after randomization (FFQ1) and again 14-16 months post-randomization (FFQ2). Lycopene-related exposures were calculated as time-varying measurements via cumulative averaging. Primary outcome was disease-free survival (DFS), defined as time from FFQ1 completion to colon cancer recurrence or death from any cause. Secondary outcomes were recurrence-free survival (RFS) and overall survival (OS). We estimated associations of lycopene-related exposures with survival via multivariable Cox proportional hazards regression. Results: In our cohort, pts with greater total lycopene intake tended to be slightly younger and of male sex and White race, have more left-sided tumors, and report higher caloric intake and physical activity engagement. Over median follow-up of 6.0 (IQR: 5.0-6.1) years, we observed 466 DFS, 395 RFS, and 300 OS events. Pts in the highest relative to lowest quintiles of total lycopene intake experienced significantly improved DFS (HR: 0.60 [95% CI: 0.44-0.83]; P trend =0.006), RFS (HR: 0.58 [95% CI: 0.41-0.82]; P trend =0.007), and OS (HR: 0.60 [95%CI: 0.40-0.89]; P trend =0.02). Similar findings were observed for dietary lycopene intake. Pts consuming >1 serving/day compared to 1 serving/week of all lycopene-containing foods did not experience significantly improved survival. However, when considering only tomato-based foods, we observed a trend toward improved survival (HR for DFS: 0.61 [95% CI: 0.38-0.96]; P trend =0.12). Conclusions: Greater lycopene consumption with or without supplementation was associated with lower risk of colon cancer recurrence and death which may be largely driven by tomato-based foods. Our findings may inform clinical nutrition recommendations for pts with colon cancer, with higher intake of tomato-based foods (>1 serving per day) potentially improving colon cancer survival. Future studies, especially interventional trials, are needed to validate our findings. Support: U10CA180821, U10CA180882, U24CA196171; Pfizer; https://acknowledgments.alliancefound.org.
Accelerating national burden of pancreatic cancer in the United States: Contemporary real-world trends, demographic disparities, and exploratory ARIMA projections from a federated electronic health record network.
e16469 Background: Pancreatic cancer remains among the most lethal malignancies worldwide, with limited improvement in survival despite therapeutic advances. Contemporary real-world data characterizing recent diagnosis acceleration, demographic disparities, and future burden remain limited. We evaluated national trends in pancreatic cancer burden using a large federated electronic health record (EHR) network. Methods: We conducted a retrospective multicenter real-world cohort analysis using the TriNetX Research Network. Adult patients (≥18 years) with pancreatic cancer were identified using ICD-10-CM code C25. Annual newly recorded diagnosis proportions, prevalence, and incidence rates were calculated for calendar years 2020–2024 and stratified by age, sex, race, and ethnicity. New diagnoses were defined as first recorded pancreatic cancer encounters within each calendar year. Exploratory future burden projections were generated through 2028 using autoregressive integrated moving average (ARIMA) time-series modeling. Results: Between 2020 and 2024, newly recorded pancreatic cancer diagnoses increased from 0.032% (21,118 cases) to 0.046% (23,660 cases), representing a descriptive relative increase exceeding 40%. Prevalence increased from 0.101% (65,971 cases) to 0.145% (74,139 cases), reflecting rapid expansion of disease burden. Diagnosis burden increased markedly with advancing age, with the highest burden observed among individuals aged ≥65 years. Males consistently demonstrated higher diagnosis proportions compared with females. Racial stratification demonstrated higher recorded diagnosis proportions among White and Asian populations, while substantial prevalence burden persisted across all racial groups, potentially reflecting differences in healthcare utilization and access. Non-Hispanic individuals exhibited higher diagnosis and prevalence proportions compared with Hispanic individuals. Exploratory ARIMA forecasting projected continued growth in pancreatic cancer burden through 2028, with widening uncertainty intervals over time, indicating escalating long-term healthcare demand. Conclusions: Pancreatic cancer burden in the United States is rapidly increasing, with disproportionate impact among older adults and males and persistent demographic disparities. Exploratory projection modeling suggests continued expansion of disease burden in the near term. These findings highlight the urgent need for earlier detection initiatives, risk-adapted screening strategies, and healthcare system preparedness to address the growing national impact of pancreatic cancer.
Pilot RCT to study the effect of chronotherapy on gefitinib plasma concentrations and adherence in lung cancer patients.
e15144 Background: Non-small cell lung cancer (NSCLC) represents the majority of lung cancer cases, with EGFR mutations driving targeted therapy using tyrosine kinase inhibitors (TKIs) like gefitinib. Preclinical evidence indicates chronopharmacokinetic variations in TKIs due to diurnal fluctuations in CYP3A4 activity, hepatic blood flow, and glucocorticoid-EGFR crosstalk, potentially affecting bioavailability and efficacy. Clinical data on gefitinib dosing time remains scarce, prompting this clinical trial to investigate the impact of gefitinib administration timing on plasma levels in non-small cell lung cancer (NSCLC) patients with EGFR mutations. Methods: EGFR-mutated NSCLC patients (age ≥18 years, ECOG ≤2, no CYP3A4 modulators/steroids) received gefitinib 250 mg once daily (morning Group A, n = 14; evening Group B, n = 16). Plasma trough levels of gefitinib and O-desmethyl gefitinib were measured at day 15 via LC-MS/MS. Serum EGFR was quantified at baseline and 3 months via ELISA. Adherence was assessed using the BAASIS questionnaire at 1 and 3 months. Statistical comparisons used t-tests/Wilcoxon tests (p < 0.05 significant). Results: The study enrolled 30 EGFR-sensitized NSCLC patients starting gefitinib 250 mg daily, randomized to morning (8-9 AM) or evening (4-5 PM) dosing. Of 30 enrolled, 18 completed (morning n = 10, evening n = 8). Trough gefitinib levels showed no significant inter-group difference (morning: 909±851 ng/mL; evening: 811±360 ng/mL; p = 0.53), similar for metabolite (p = 0.09). Serum EGFR decreased significantly overall (276±69 to 219±65 ng/mL, p = 0.005) and in morning group (p = 0.047), but not evening (p = 0.079). No correlation linked levels to response (PR/SD/PD). Adherence was poor (5.5% fully adherent); morning patients showed better compliance trends (e.g., fewer missed doses). Conclusions: Gefitinib plasma levels were comparable between morning and evening dosing, but morning administration associated with greater EGFR reduction, suggesting potential chrono efficacy advantages. Low adherence highlights need for interventions. Larger trials validate optimal timing to enhance outcomes. Clinical trial information: CTRI/2021/09/036915.
Impact of genomic HLA class I allelic imbalance on enduring immunotherapy response in advanced non–small cell lung cancer.
8582 Background: Human leukocyte antigen class I (HLA-I) molecules are essential for neoantigen presentation and T cell recognition, yet the clinical significance of allelic imbalance within HLA-I genes (HLA-AI) in immune checkpoint inhibitors (ICIs) therapy remains undefined. Methods: Here, we established haplotype-specific, coverage-based (cHLA-AI) compatible with routine biopsy-derived sequencing, based on 292 fully heterozygous non–small cell lung cancer (NSCLC) patients with paired tumor samples from the phase III CHOICE-01 trial and confirmed in RATIONALE-304 and real-world NCC cohorts, covering both first- and later-line immunochemotherapy as well as ICI monotherapy, and complemented by analyses in surgical, pan-cancer, and longitudinal datasets to assess immune correlates and evolutionary dynamics. Results: Patients with tumor mutational burden (TMB)–low and cHLA-AI derived no benefit from first-line immunochemotherapy, whereas all other patients achieved significant survival gains (TMB-low and cHLA-AI vs. others: immunochemotherapy arm: mOS 16.53 vs. 29.57 months, HR = 2.29, 95% CI 1.59–3.30, p < 0.001,interaction P = 0.019; mPFS 5.59 vs. 9.92 months, HR = 2.02, 95% CI 1.43–2.90, p < 0.001, interaction P = 0.016). These findings were validated in the RATIONALE-304 and RATIONALE-307 trials and independent real-world cohorts. Incorporating cHLA-AI with pathology, PD-L1 and TMB significantly improved 2-year OS prediction (DeLong’s P = 0.003). Multi-omic profiling linked cHLA-AI to active DNA damage response signalings, high TMB -intratumor heterogeneity (ITH) -chromosomal instability (CIN) phenotype, immune-cold microenvironments, and failure of on-treatment TCR clone expansion, while longitudinal sampling revealed its late, branching emergence under immune pressure. Pan-cancer profiling (N = 5,989) demonstrated consistent associations with high TMB-ITH-CIN phenotype and proliferative activity (Ki-67 index). Conclusions: Collectively, these results establish cHLA-AI as a pivotal biomarker bridging genomic instability, immune evasion, and therapeutic outcomes, providing a framework for stratified immunotherapy response in non–small cell lung cancer and beyond.
Trends and disparities in arrhythmia-related mortality among older adults with cancer in the United States (1999-2023).
e24008 Background: Arrhythmias, or irregular heart rhythms, are common in patients with cancer. They can result from the cancer itself, side effects of treatments, or other health factors. These heart rhythm problems may increase the risk of complications and affect the patient’s quality of life. Understanding how arrhythmias affect cancer patients is important, as they can influence treatment choices, outcomes, and overall health. Methods: We analyzed CDC WONDER data to estimate age-adjusted mortality rates (AAMRs) for cancer (ICD-10 C00–D48) among adults aged ≥65 years with arrhythmias (ICD-10 I44, I45, I47,I48, and I49). Temporal trends and average annual percent changes (AAPCs) were assessed using Joinpoint regression, stratified by sex, race/ethnicity, and geographic factors, including urbanization and U.S. census region. Results: A total of 364,298 deaths related to arrhythmia occurred among cancer patients, with most deaths occurring in medical facility inpatients. Overall, the age-adjusted mortality rate (AAMR) increased from 25 (95% CI: 24.47–25.53) in 1999 to 47.85 (95% CI: 47.27–48.44) in 2023 (AAPC: 2.70; 95% CI: 2.27–3.14, p < 0.001). The trend rose significantly by 2017 (APC: 1.86; p < 0.001) and continued to increase from 2017 to 2021 (APC: 6.97; p = 0.001). The increase in mortality was slightly more pronounced in women than in men (AAPC: 2.71 vs. 2.45). The highest incidence rates were observed among non-Hispanic (NH) Whites, followed by NH Blacks or African Americans, Hispanics and Latinos, and NH Asians and Pacific Islanders. Geographic disparities were evident, with the Midwest experiencing the greatest impact and the South the least. Non-metropolitan areas consistently showed higher AAMRs compared to metropolitan areas (AAPC: 3.66 vs. 2.25). From 1999–2020, Maryland, and from 2020–2023, Minnesota, ranked in the top 90th percentile. Conclusions: Arrhythmia-related deaths among cancer patients have steadily increased from 1999 to 2023, with higher rates in women and non-Hispanic Whites. The Midwest and non-metropolitan areas were most affected, showing notable geographic disparities. Focused monitoring and management are essential for the most vulnerable groups. Deaths and average annual percentage change (AAPC) per 100,000 population for arrhythmia and cancer trends, 1999-2023. Variable Deaths AAPC (95%CI) Overall 364,298 2.70 (2.27 to 3.14) Male 205,780 2.45 (1.83 to 3.08) Female 158,518 2.71 (2.39 to 3.04) NH White 70,531 3.01 (2.58 to 3.45) NH Asians 6,496 2.36 (1.25 to 3.49) Midwest 87,457 2.37 (1.89 to 2.86) South 125,475 3.48 (3.15 to 3.82) Metropolitan areas 232,422 2 25 (1.86 to 2.64) Non- Metropolitan areas 57,634 3.66 (2.90 to 4.34)
Double lung transplantation in patients with metastatic lung-limited non–small cell lung carcinoma (NSCLC): A case series.
e20777 Background: The role of double lung transplantation (DLT) in patients with advanced bilateral lung-limited non-small cell lung cancer (NSCLC) has been a subject of debate. We present prospective data from the DLT registry for lung-limited malignancies (DREAM) study (NCT05671887) cohort A evaluating DLT as a therapeutic strategy for this patient population. Methods: Patients with advanced bilateral lung-limited NSCLC who underwent DLT at Northwestern Memorial Hospital between September 2021 and December 2025 were included in the DREAM study cohort A. Patients with extrapulmonary disease were excluded. The primary indications for DLT were disease refractory to systemic therapies, with or without respiratory failure. Clinical outcomes, perioperative safety, and recurrence patterns were evaluated. Results: In total, 18 patients with advanced bilateral lung-limited NSCLC were included. The median age was 58.5 years (range 28-74). 14 patients (78%) were White, one was Asian (6%), one was Black (6%), and two were others (11%). 11 (61%) were female. Nine (50%) had a history of smoking. 12 patients (67%) had invasive mucinous adenocarcinoma histology. All patients experienced disease progression on standard-of-care treatments, with or without participation in clinical trials. 16 patients remain alive at the cut-off date of January 1st, 2026. The median follow-up duration and overall survival since DLT is 15.5 months (range: 1-49). The median duration on the DLT waitlist was 12 days (range: 3-59). There was no 30-day post-transplant mortality. One patient developed acute humoral rejection, which was successfully treated. All patients were discharged on room air after DLT. Three patients had lymph node-positive disease at explant and received adjuvant chemotherapy. Six patients developed recurrence (cases #1, 6, 8, 9, 11, 13). Two patients (cases #1 and 13) had lung recurrence. The other four patients (cases #6, 8, 9, 11) had bone metastases (case #6 also with brain metastasis). One achieving remission of pulmonary recurrence after SBRT (case #1) but died of COVID-19 infection at 49 months post-DLT. One patient died of presumed massive pulmonary embolism during adjuvant chemotherapy at 5 months post-DLT. Conclusions: DLT for bilateral lung-limited NSCLC is feasible, with acceptable perioperative safety, absence of early cancer-related deaths, and meaningful gains in respiratory function and quality of life. Recurrence remains a concern but can be managed with post-transplant therapies. These prospective results suggest that DLT may provide functional and survival benefits in a highly selected population otherwise facing terminal outcomes. The DREAM cohort A continues to define the safety of DLT in this population prospectively. Clinical trial information: NCT05671887 .
Observation versus maintenance PD-1 inhibitor therapy after clinical complete response in dMMR/MSI-H colorectal cancer managed with non-operative management: A multicentre cohort study.
3502 Background: Patients with mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) colorectal cancer (CRC) who achieve a clinical complete response (cCR) after PD-1 inhibitor therapy may undergo non-operative management (NOM) with active surveillance. We aimed to assess the necessity of maintenance immunotherapy after achieving cCR, with a focus on survival outcomes and the burden of immune-related toxicity. Methods: A multicentre observational cohort study was conducted at five tertiary hospitals in China between Jan 1, 2018, and March 21, 2025. Patients with dMMR/MSI-H CRC who achieved cCR after PD-1 inhibitor therapy and entered NOM were included. Patients were stratified into an observation group （discontinue PD-1 inhibitor after cCR) and a maintenance group (received ≥2 cycles of PD-1 inhibitors after cCR). Disease-free and overall survival were compared between groups using Kaplan–Meier methods with log-rank test, and local regrowth, distant metastasis, and immune-related adverse events were assessed. Results: Among 318 patients treated with PD-1 inhibitors, 195 (61·3%) achieved cCR. A total of 129 patients were analysed (observation n = 66; maintenance n = 63), including 58 with rectal cancer, 61 with colon cancer, and 10 with synchronous dual primary tumours; 14 had distant metastases at diagnosis. Clinical complete response was assessed with endoscopy and pelvic MRI/CT along with digital rectal examination for rectal cancer, and endoscopy with contrast-enhanced CT or PET/CT for colon cancer. Median PD-1 inhibitor exposure to achieve cCR was eight cycles in both groups; 69·8% achieved cCR within eight cycles. Median follow-up was 3·2 years (IQR 2·0–4·0). Local regrowth occurred in two patients in the observation group and none in the maintenance group, and no distant metastases were observed. The 3-year DFS was 96·4% (95% CI 91·6–100·0) in the observation group and 98·4% (95% CI 95·2–100·0) in the maintenance group (log-rank p = 0·55). The 3-year OS was 100·0% (95% CI 100·0–100·0) versus 98·4% (95% CI 95·2–100·0) (p = 0·34). Any-grade irAEs occurred in 42/66 (63·6%) versus 44/63 (69·8%); grade 3 irAEs were numerically higher with maintenance (7/63 [11·1%] vs 2/66 [3·0%]; p = 0·091). Conclusions: To our knowledge, this is the largest series of dMMR/MSI-H CRC patients achieving cCR after PD-1 inhibitor therapy and managed with NOM. Maintenance therapy after cCR did not provide a clear survival advantage but was associated with a higher burden of immune-related toxicity, supporting treatment discontinuation with close surveillance.
Radical cystectomy vs bladder-sparing therapy in very high-risk non–muscle-invasive bladder cancer: Real-world 5-year outcomes and immune checkpoint inhibitor–based substrategy analysis.
e16610 Background: While early radical cystectomy (RC) is recommended by contemporary guidelines for very high-risk non–muscle-invasive bladder cancer (VHR-NMIBC), a substantial proportion of patients are not ideal candidates for RC or decline surgery; therefore, bladder-sparing therapy (BST) approaches remain clinically relevant, including intravesical BCG and emerging immune checkpoint inhibitor–based (ICI-based) strategies in BCG-naïve NMIBC. However, follow-up data on ICI-based strategies in BCG-naïve NMIBC remain limited. Therefore, we compared 5-year survival outcomes of RC vs BST and examined BST substrategies, focusing on whether ICI-based approach improves intravesical control. Methods: This multi-center retrospective cohort (2019–2025) included patients with pathologically confirmed very high-risk NMIBC per EAU risk stratification across 13 medical centers in China. Treatments were RC (± pelvic lymph node dissection) or BST (ICI-based systemic therapy or intravesical BCG). Endpoints were 5-year progression-free survival (PFS; ≥T2 progression, regional/distant metastasis, or death), cancer-specific survival (CSS), and intravesical recurrence–free survival (IVRFS; intravesical recurrence [Ta/T1/CIS], persistent disease on re-TURBT, or death before intravesical failure). Kaplan–Meier estimated 5-year rates. Multivariable Cox models adjusted for age, sex, stage (Ta/T1), CIS, tumor size/multifocality, and variant histology. Results: Among 379 patients, 186 received RC and 193 received BST (ICI-based n = 93; BCG n = 100). Median follow-up was 62.3 months (reverse KM; 95%CI 60.07–64.17). RC vs BST showed no significant differences: 5-year PFS 94.0% vs 87.5% (HR 0.59, 95%CI 0.23–1.40, P = 0.44); CSS 95.7% vs 95.7% (HR 1.65, 95%CI 0.52–5.24, P = 0.84); IVRFS 87.1% vs 82.2% (HR 0.99, 95%CI 0.48–2.00, P = 0.87). Within BST, ICI-based vs BCG demonstrated no significant differences in PFS and CSS but significantly improved IVRFS: PFS 89.0% vs 87.6%; CSS 96.9% vs 97.0%; IVRFS 67.5% vs 60.5% (HR 0.34, 95%CI 0.17–0.69, P = 0.003). Compared with RC, ICI-based BST showed no significant differences in PFS, CSS, or IVRFS (all P > 0.05), with a 5-year bladder preservation rate of 93.78%. Conclusions: In this real-world cohort of patients with BCG-naïve very high-risk NMIBC, RC and BST had broadly similar 5-year PFS, CSS, and IVRFS. Within BST, while maintaining similar PFS and CSS, an ICI-based strategy provided significantly better intravesical recurrence disease control than BCG, supporting ICI-based BST as a meaningful bladder-preserving option for selected patients.
Vessel branching patterns quantified by artificial intelligence as a novel prognostic biomarker in advanced renal cell carcinoma: A post-hoc analysis of the CM914 trial.
4523 Background: Current adjuvant risk stratification in renal cell carcinoma (RCC) relies primarily on TNM-staging. However, disease progression and response to therapy are driven by biological subgroups reflected in tumor vessel architecture. We therefore analyzed vessel branching patterns in 1098 adjuvant RCC patients to evaluate whether an AI-derived biomarker quantifying vascular architecture improves prognostic discrimination beyond TNM. Methods: Digital images of representative tumor tissue and oncologic outcomes were obtained from the CM914 trial (NCT03138512). Tumor tissue was annotated by a pathologist to define vessel branching patterns as high-branching (HB) or low-branching (LB) patterns. HB and LB patterns were quantified using a deep learning model as the tumor-wide fraction of HB in digitized H&E whole-slide images from 1098 of 1641 evaluable patients (67%). Based on the tumor-wide HB fraction, patients were classified into risk groups using a data-driven cut-off optimized for Kaplan–Meier survival analysis, allowing comparison with TNM-based risk strata (PT2a, G3/G4, N0, M0 / PT2b, G ANY, N0, M0 / PT3, G ANY, N0, M0; intermediate-high risk, n=1016 vs PT4, G ANY, N0, M0 / PT ANY, G ANY, N1, M0; high risk, n=82). Risk stratification performance for overall survival (OS) and disease-free survival (DFS) was compared between branching pattern–based and TNM-based risk groups using Cox regression, Kaplan–Meier analysis, and concordance indices. Results: Higher tumor-wide HB fractions were associated with improved DFS and OS, showing a continuous effect on prognosis. Each 10% increase in HB fraction reduced risk of recurrence and death (DFS HR 0.92, 95% CI 0.89–0.95; OS HR 0.89, 95% CI 0.83–0.95; both p<0.005). Kaplan–Meier analyses showed longest survival in the 4 th quartile (OS HR 0.39, 95% CI 0.21–0.71, p=0.002; DFS HR 0.47, 95% CI 0.35–0.64, p<0.0001). This threshold defined the 75th percentile cutoff for risk stratification, separating patients into intermediate risk (≥74% HB; n=275) vs high risk (<74% HB; n=823) groups. High risk patients had an increased risk of recurrence and death (DFS HR 2.11, 95% CI 1.57–2.84, C-Index 0.57; OS HR 2.57, 95% CI 1.28–4.32, C-Index 0.56, both p<0.005). TNM-based risk showed lower prognostic discrimination (DFS: HR 1.95, 95% CI 1.39–2.74, C-Index 0.53; OS: HR 2.55, 95% CI 1.52–4.30, C-Index 0.55, both p<0.005). Combining branching-based risk with TNM improved DFS and OS discrimination compared with TNM alone (C-Index 0.59). Conclusions: Higher fractions of high-branching vessels are associated with improved DFS and OS, potentially enabling risk stratification beyond conventional TNM criteria in RCC. While prospective validation is required to confirm clinical applicability, these results suggest high-branching vessel architecture represents a promising prognostic feature.
A comprehensive evaluation of the effectiveness of the Geriatric 8 screening tool in Japanese patients with non–small cell lung cancer: Results from the ENSURE-GA study, a cluster-randomized phase III clinical trial.
8599 Background: The Geriatric 8 (G8) is a widely utilized screening tool globally for assessing functional status in elderly cancer patients, with a score of 14 or lower indicating a positive result. Previous studies have reported that G8-positive patients are at a higher risk of mortality and experiencing Grade 3 or higher adverse events (AEs). At ASCO 2024, we reported that the G8 positivity rate exceeded 80% among Japanese patients aged 75 and older with non-small cell lung cancer (NSCLC), suggesting a potential issue with its sensitivity in this population. In the present study, we conducted a further detailed analysis of the scoring patterns for individual G8 items and their association with the incidence of AEs. Methods: The ENSURE-GA study was a cluster-randomized phase III clinical trial involving 1,021 patients aged 75 years and older with non-small cell lung cancer (NSCLC). Participating institutions were cluster-randomized into either the intervention group or the control group. All patients underwent a standardized Geriatric Assessment (GA) prior to the initiation of treatment. From this cohort, 1,001 patients who underwent G8 assessment were identified for analysis. We evaluated the association between the scoring patterns (loss of points) for each G8 item and the frequency and severity of adverse events. Results: The ROC curve for G8 regarding the occurrence of grade 3 or higher adverse events in cases receiving cytotoxic chemotherapy yielded an AUC of 0.525, indicating no discriminatory ability. Among the eight components of the G8 screening tool, self-rated health status ("In comparison with other people of the same age, how does the patient consider their health status?") showed the highest rate of point loss at 72.0% (656/911), followed by polypharmacy at 67.5% (615/911) and Body Mass Index (BMI) at 61.9% (564/911).The G8 score did not correlate with the severity of adverse events. Conclusions: The G8 is a valuable screening instrument, but our findings suggest the need for optimization, including the establishment of cancer-specific and race-specific cut-offs, as well as the implementation of weighted scoring for its components. Clinical trial information: UMIN0000037590.