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The 30-15 intermittent fitness test in male futsal players: reliability and validity properties

Mechanism-selective inhibition of α-synuclein aggregation by the chaperone-like BRICHOS domain

Incidence trends and factors affecting survival in thymic carcinoma: Insights from SEER data.

e20169 Background: Thymic carcinoma is a rare neoplasm, accounting for less than 0.01% of new cancer diagnoses annually. It carries a poorer prognosis compared to its counterpart thymoma. This study aims to identify demographics, incidence trends, and factors affecting overall survival (OS) in thymic carcinoma. Methods: We performed a retrospective cohort analysis using the Surveillance, Epidemiology, and End Results (SEER) database, including patients diagnosed with thymic carcinoma from 2000 to 2022. Demographics and treatment data were summarized using descriptive statistics. Cox proportional regression analysis was used to identify factors impacting OS. Results: Between 2000 and 2022, a total of 7,309 patients were diagnosed with thymic carcinoma. The highest incidence occurred in patients under 60 years old at 43.6%. However, compared with patients under 60, those aged 60–69 had a 39% higher risk of death (HR = 1.39, 95% CI 1.27–1.52), and patients ≥70 had more than twice the risk. Males comprised 53.4% of cases, and Caucasians accounted for 66.1%. Most patients lived in urban areas (92.3%) and had an annual income >$60,000 (91.4%). Married patients (59.7%) had better OS than their unmarried counterparts. The incidence trends revealed a significant increase from 2000 to 2022. The incidence rates were: 16.4% (2000 -2005), 18.3% (2006 -2010), 19.5% (2011 - 2015), and 45.8% (2016-2022). However, the survival rates improved over time (See table). Regarding treatment, patients who received surgery and radiation were associated with better OS; interestingly, receipt of chemotherapy was not associated with better OS. Hazard ratios for all factors are summarized in the Table. Conclusions: This, the largest study to date on thymic carcinoma, demonstrates a rising incidence from 2000 to 2022 alongside improved OS. Patients diagnosed in the most recent period (2016–2022) had a restricted mean survival time of 15.02 years, indicating that, on average, they survived approximately 15 years within the study’s observation period, despite median survival not being reached due to too few events. These findings provide insights into the demographics and clinical factors influencing survival in this rare malignancy. Variable Group Hazard ratio Gender Male vs Female 1.19 (CI 1.11-1.28) Age 60-70 years vs <60 years 1.39 (CI 1.27-1.52) >70 years vs < 60 years 2.43 (CI 2.24-2.68) Year of diagnosis (2006-2010) vs (2000-2005) 0.91 (CI 0.83-1.00)* (2011-2015) vs (2000-2005) 0.93 (CI 0.83-1.03)* (2016-2022) vs (2000-2005) 0.84 (CI 0.75-0.94) Income <30K vs >60K 1.31 (CI 0.81-2.11)* 30-60K vs >60K 1.24 (CI 1.1-1.4) Race White vs Black 0.98 (CI 0.88-1.08)* Other vs Black 0.91 (CI 0.8-1.04) Marital status Yes vs No 1.22 (CI 1.14-1.31) Chemotherapy Yes vs No 1.91 (CI 1.7-2.05) Surgery Yes vs No 0.26 (CI 0.24-0.28) Radiation Yes vs No 0.83 (CI 0.77-0.89) p-value < 0.001 except for *non significant.

Expanding cfDNA capture beyond nucleosome-sized fragments to enhance liquid biopsy performance.

e15062 Background: Liquid biopsy is a non-invasive diagnostic approach used for early cancer detection, disease monitoring, and minimal residual disease (MRD) assessment. Accurate liquid biopsy results require comprehensive recovery of circulating cell-free DNA (cfDNA) to capture molecular diversity in low-input and low–tumor burden samples. However, conventional cfDNA purification and double-stranded DNA library preparation workflows are optimized for nucleosome-sized fragments and may systematically exclude ultra-short and single-stranded cfDNA species that may be relevant to cancer diagnostics, potentially limiting assay sensitivity and contributing to false-negative results. Methods: In this study, cfDNA was isolated from plasma, serum, and saliva using a magnetic bead-based purification workflow (MAGicBead) and compared with commercially available cfDNA extraction methods under clinically relevant input conditions. Libraries were prepared using a single-stranded DNA–compatible workflow to capture both double- and single-stranded cfDNA. Fragment size distributions and unique molecular characteristics were evaluated by sequencing-based analysis. To assess clinical usability, the workflow was adapted for hybrid-capture targeted enrichment without modification to standard probe designs and evaluated for compatibility with Agilent SureSelect, TWIST, and IDT xGen platforms. Feasibility and enrichment performance were assessed in plasma from lung cancer patients and healthy controls using standard sequencing and bioinformatics pipelines. Results: The optimized workflow demonstrated improved cfDNA recovery relative to conventional methods and consistently captured ultra-short cfDNA fragments (approximately 35–75 bp) that were not detected using standard workflows. Enzymatic digestion suggested that these fragments were predominantly single-stranded. The workflow was compatible with multiple commercial targeted enrichment platforms, enabling simultaneous capture of nucleosome-sized and ultra-short cfDNA within a single assay. Differences in the relative abundance of ultra-short cfDNA fragments were observed between cancer and healthy plasma samples. In saliva, concurrent recovery of host and microbial DNA supported multi-omic profiling from a single library preparation. Conclusions: This clinically adaptable workflow overcomes fragment size bias inherent to standard liquid biopsy assays and has the potential to enhance sensitivity across multiple liquid biopsy applications, including cancer detection and disease monitoring.

Cancer stigma in low- and middle-income countries: A scoping review of frameworks, measurement approaches, and interventions.

1590 Background: The incidence and mortality rates of cancer are rising fastest in low- and middle-income countries (LMICs). While cancer early detection and treatment are increasingly available in LMICs, several care barriers contribute to persistent disparities in survival outcomes. One identified barrier is stigma regarding cancer and its treatment approaches. However, there is limited literature on validated measurement tools for cancer stigma and interventions to address this stigma in LMICs. Methods: A systematic search of six electronic databases (OVID Medline, Embase, Web of Science, EBSCO: Africa-Wide Information, EBSCO: Global Health, and WHO Global Index Medicus/ African Index) was performed on August 17, 2023, and updated on November 20, 2025. Two reviewers independently screened 3174 titles/abstracts and 425 full-text articles. Three researchers extracted data from 129 eligible articles following sufficient agreement on pilot testing. The findings were synthesized using descriptive statistics and content analysis based on the Health Stigma and Discrimination framework. Results: Of the 129 articles, the study types included: cross-sectional surveys (109, 84%), randomized controlled trials (9, 7%), prospective cohorts with an intervention (9, 7%), one prospective cohort with no intervention, and one retrospective study. The studies were from 30 LMICs, with the plurality from China (59, 46%), followed by Turkey (12, 9%) and Kenya (10, 8%). Many studies focused on general cancer stigma (rather than a particular type of cancer) (34, 26%) and involved patients with cancer (90, 70%) or the general community (22, 17%). The studies commonly assessed stigma at the individual (113, 88%) and interpersonal (97, 75%) socio-ecological levels. 126 (98%) studies included a quantitative cancer stigma measurement tool, with the most common established tools being the Social Impact Scale (SIS, 33, 26%) and the Cancer Stigma Scale (CASS, 13, 10%). However, many used other adapted cancer stigma or HIV stigma scales. 41 (33%) studies were validation studies of a tool in the local context, 58 (46%) used previously validated tools, and 27 (21%) did not mention local validation. There were 18 studies with interventions, most of which focused on educational approaches, and 15 (83%) were published since 2021. Conclusions: This review demonstrates a wide variation in tools and validation practices in studies measuring cancer stigma in LMICs. Effective comprehensive interventions remain lacking and should be the focus of future studies.

CAREFOL: A phase 3, randomized, open-label, multicenter trial of camrelizumab and rivoceranib with or without intravenous FOLFOX chemotherapy as first-line treatment for unresectable hepatocellular carcinoma.

TPS4257 Background: The combination of camrelizumab (an anti-PD-1 IgG4 monoclonal antibody) and rivoceranib (a VEGFR2-TKI) is a standard of care, first-line (1L) therapy for advanced hepatocellular carcinoma (HCC). However, immune therapy resistance leads to ineffective initial treatment and difficulty in maintaining long-term efficacy in some patients. Several studies have shown that oxaliplatin and fluorouracil can induce immunogenic cell death in tumor cells and induce antitumor immune response in the body. Intravenous FOLFOX chemotherapy may regulate the liver tumor microenvironment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase II VIC-TRIPLETS study (NCT05412589). Here we present the design of a phase III randomized controlled study. Methods: This investigator-initiated, phase III, randomized, open-label, multicenter trial (NCT06280508) aims to compare the efficacy and safety of camrelizumab and rivoceranib combined with (CAREFOL) or without intravenous FOLFOX chemotherapy (CARE) as first-line treatment for unresectable HCC. Eligible patients are aged at least 18 years, with unresectable or metastatic HCC, no previous systemic treatment, with BCLC stage B or C disease (which is not amenable to or had progressed after surgical or locoregional therapy), at least one measurable lesion per RECIST 1.1 criteria, Child-Pugh class A liver function, an ECOG performance status of 0 or 1, and adequate organ function. Approximately 326 Participants will be randomly assigned (1:1) using a centralized interactive response system. Randomization is stratified by presence of extrahepatic metastasis (yes vs no), macrovascular invasion (Vp0-3 vs Vp4), and baseline α-fetoprotein level ( < 400 ng/mL vs ≥400 ng/mL). The experimental group consisted of camrelizumab 200 mg intravenously every 3 weeks plus rivoceranib 250 mg orally once daily combined with 21-day cycles of intravenous FOLFOX chemotherapy (oxaliplatin 85 mg/m 2 , levofolinate 200 mg/m 2 , 5-fluorouracil bolus 400 mg/m 2 on day 1, and 5-fluorouracil infusion 2400 mg/m 2 for 46 hours; up to 6 cycles). The control group is camrelizumab plus rivoceranib (same as experimental group). The dual primary endpoints are investigator-assessed progression-free survival per RECIST v1.1 and overall survival. Secondary endpoints include objective response rate, disease control rate, duration of response, surgical conversion rate, time-to-treatment failure, safety. The trial is currently screening eligible patients. Clinical trial information: NCT07267806 .

Differences in treatment outcomes among <i>EGFR</i> mutations, fusion oncogenes, and other actionable alterations in NSCLC: A large Japanese real-world cohort.

e20712 Background: Molecular targeted therapies have transformed the management of non–small cell lung cancer (NSCLC) with actionable genomic alterations. However, direct comparisons of treatment outcomes across different genomic subtypes within a single real-world cohort remain limited. We evaluated the relative efficacy and safety of targeted therapies across major actionable genomic alterations in a large Japanese real-world population. Methods: This multicenter retrospective study included 810 consecutive Japanese patients with advanced or recurrent NSCLC harboring actionable genomic alterations who received molecular targeted therapy between 2017 and 2023. Patients were classified into three genomic groups: EGFR mutations (Group A, n = 659), fusion oncogenes involving ALK/ROS1/RET (Group B, n = 106), and other actionable alterations including MET exon 14 skipping, BRAF V600E, and KRAS G12C (Group C, n = 45). Treatment outcomes, including objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety, were analyzed using Kaplan–Meier methods and multivariable Cox regression. Results: The median follow-up was 24.9 months overall (Group A 25.6, Group B 27.3, Group C 16.1). A total of 580 progression events and 398 deaths were observed. ORR differed significantly among groups (74.1% in Group A, 85.8% in Group B, and 68.9% in Group C; P = 0.014). Median PFS was 17.5 months in Group A, 42.5 months in Group B, and 9.2 months in Group C (P &lt; 0.001). Median OS was not reached in Group B, compared with 39.3 months in Group A and 22.7 months in Group C (P &lt; 0.001). In multivariable analyses adjusting for clinical covariates, genomic subgroup remained independently associated with both PFS and OS, with fusion-driven tumors demonstrating consistently superior outcomes. EGFR-mutated tumors showed intermediate outcomes, whereas Group C exhibited limited efficacy and higher treatment discontinuation due to adverse events. Conclusions: In this large Japanese real-world cohort, a clear hierarchy of therapeutic benefit across actionable genomic alterations was observed. Fusion oncogene–driven NSCLC derived exceptional and durable benefit from targeted therapy, EGFR-mutated tumors demonstrated intermediate outcomes, and MET exon 14 skipping, BRAF V600E, and KRAS G12C mutations remained associated with limited efficacy and higher toxicity. These findings underscore the clinical importance of genomic subtype–based treatment strategies and highlight unmet needs in selected molecular subsets.

Clinical impact of <i>TOP1</i> alterations on outcomes to topoisomerase-I–directed therapies across chemotherapy and antibody-drug conjugates.

e15044 Background: Topoisomerase-I (TOP1)–directed therapies are used broadly in solid tumors, including irinotecan-based chemotherapy and TOP1-payload antibody–drug conjugates (ADCs). While TOP1 alterations have been implicated in resistance to TOP1-payload ADCs, their real-world clinical impact across therapeutic classes remains incompletely defined. Methods: We conducted a retrospective clinico-genomic analysis of the MSK-CHORD 2024 cohort integrating baseline tumor sequencing with longitudinal treatment timelines. Baseline TOP1 alteration status was defined on the earliest available tumor sequencing as (i) nonsynonymous TOP1 mutation and/or (ii) focal TOP1 copy-number alteration (CNA; amplification or deep deletion). We evaluated patients who received, after baseline sequencing, either (1) irinotecan-based chemotherapy (irinotecan or liposomal irinotecan) and/or (2) TOP1-payload ADCs (sacituzumab govitecan or fam-trastuzumab deruxtecan). Real-world effectiveness endpoints were time-to-next-treatment (TTNT) and time-to-treatment discontinuation (TTD) from first exposure to each therapy class. Outcomes were summarized with Kaplan–Meier methods and compared by TOP1 status using the log-rank test. Results: Among 24,950 sequenced patients, 430 (1.7%) had baseline TOP1 alterations (197 mutations, 235 focal CNAs, and 2 overlap). After baseline sequencing, 3,009 patients received irinotecan-based chemotherapy (64 TOP1-altered) and 503 received TOP1-payload ADCs (6 TOP1-altered). For irinotecan-based chemotherapy, median TTNT was 5.5 months (TOP1-altered) vs 4.1 months (TOP1-wild-type); median TTD was 5.4 vs 3.3 months, respectively. For TOP1-payload ADCs, median TTNT was 2.8 months (TOP1-altered) vs 4.5 months (TOP1-wild-type); median TTD was 2.2 vs 4.1 months, respectively (exploratory given small TOP1-altered ADC sample size [n = 6]). Conclusions: In a large real-world clinico-genomic cohort, baseline TOP1 alterations were uncommon but associated with class-dependent differences in effectiveness of TOP1-directed therapies. The directionality of association differed between irinotecan-based chemotherapy and TOP1-payload ADCs, supporting further evaluation of TOP1 genomics along with tumor context and treatment line for therapeutic selection and sequencing, particularly in ADC-treated populations.

Neoadjuvant therapy versus upfront surgery for resectable/borderline resectable pancreatic ductal adenocarcinoma: Systematic review and meta-analysis of randomized controlled trials.

e16461 Background: Neoadjuvant strategies are becoming increasingly popular in resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC), but randomized evidence has been inconsistent. This updated RCT-only meta-analysis incorporates phase III data (CISPD-1) and the finalized Prep-02/JSAP05 report. We aim to compare neoadjuvant therapy (NAT) versus upfront surgery (UFS) in resectable/borderline resectable PDAC regarding efficacy and safety. Methods: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched for RCTs enrolling patients with resectable/borderline resectable PDAC and comparing NAT followed by surgery vs UFS (with adjuvant therapy as planned in each trial). Overall survival (OS) was the primary endpoint. Disease-control endpoints including disease-free survival (DFS), recurrence-free survival (RFS), event-free survival (EFS), or progression-free survival (PFS) were pooled as a single time-to-event outcome (HRs); binary outcomes were pooled as RRs using random-effects inverse-variance models; heterogeneity was assessed with I². Results: Five RCTs (n = 1,121) were included. NAT did not significantly improve OS, HR 0.80 (95% CI 0.61-1.05; I² = 67.2%). Across four RCTs reporting disease-control endpoints including DFS, RFS, EFS or PFS, NAT was associated with improved disease control HR 0.80 (95% CI 0.64-0.99; I² = 55.5%). Among patients who underwent resection, NAT increased margin-negative (R0) resection rates RR 1.26 (95% CI 1.06-1.49; I² = 74.9%) but reduced the likelihood of reaching resection overall RR 0.93 (95% CI 0.88-0.98; I² = 14.4%). NAT was associated with higher severe adverse events RR 1.39 (95% CI 1.15-1.67; I² = 0%). Conclusions: NAT for resectable/borderline resectable PDAC improved disease-control outcomes and margin-negative resection rates, but was associated with a reduction in patients ultimately undergoing resection. Moreover, NAT was associated with an increased risk of severe adverse events and no clear OS benefit. Substantial heterogeneity suggests effects may differ by regimen and baseline resectability; longer follow-up is needed. Trial-level counts (trial-defined denominators). Notes: R0 denominators are resected/pathology sets (PREOPANC reports R0 among PDAC resections). AE denominators are trial-defined safety sets (PREOPANC reports serious AEs). NR=not reported. Trial Randomized NAT/UFS ResectedNAT/UFS R0 (n/N) Grade ≥3/serious AEs (n/N) Jang 2018 27/23 17/18 14/17 vs 6/18 NR PREOPANC 2022 119/127 72/92 49/68 vs 35/82 62/119 vs 52/127 NORPACT-1 2024 77/63 63/56 35/63 vs 22/56 42/73 vs 19/47 Prep-02/JSAP05 2026 182/179 157/156 143/157 vs 134/156 NR CISPD-1 2025 162/162 135/149 118/135 vs 119/149 68/143 vs 35/114 Total 567/554 444/471 359/440 vs 316/461 172/335 vs 106/288

Zongertinib in HER2-altered colorectal cancer: A pooled analysis of colorectal cancer patients from two clinical trials.

3538 Background: Zongertinib, an irreversible TKI, selectively inhibits HER2 while sparing wild-type EGFR, thereby minimizing associated toxicities. Here, we present a pooled analysis of a subgroup of patients (pts) with HER2-positive colorectal cancer (CRC) who received zongertinib monotherapy in Phase Ia of a dose-escalation/expansion trial (NCT04886804) or in the ongoing Phase II Beamion PANTUMOR-1 trial (NCT06581432), as well as supporting preclinical data. Methods: Preclinical antitumor activity of zongertinib as monotherapy or in combination with other HER2-directed agents was assessed in commercially available HER2 -amplified mouse PDX models of CRC. Phase Ia of NCT04886804 enrolled pts with advanced solid tumors and HER2 alterations (mutations, amplification, or overexpression) who had exhausted all other standard treatment options. Beamion PANTUMOR-1 includes pts with previously treated HER2-positive (amplification or overexpression) or HER2 -mutant solid tumors. Pts in NCT04886804 received escalating doses of zongertinib (15 mg BID or 180–360 mg QD); pts in Beamion PANTUMOR-1 received zongertinib 120 mg QD. Efficacy (investigator-assessed objective response rate [ORR]; RECIST v1.1) and safety (incidence of adverse events [AEs]; CTCAE v5.0) were assessed. Results: In HER2 -amplified PDX CRC models, zongertinib monotherapy and in combination with other HER2-directed agents led to tumor growth inhibition or regression, with greater antitumor activity observed with the combinations. A total of 20 pts with HER2-positive CRC (10 from each trial) received zongertinib. Pts had a median age of 53 years (range: 36–70) and had received a median of 2.5 lines of prior systemic therapy. A total of 8 pts (6 from NCT04886804 and 2 from Beamion PANTUMOR-1) had received ≥1 prior HER2-directed therapy, including trastuzumab, pertuzumab, or T-DXd. Median treatment duration with zongertinib was 5.1 months (range: 0–18). The confirmed ORR was 45% (n = 9; all partial responses). A further 9 (45%) pts achieved stable disease, giving a disease control rate of 90%. At the time of analysis, 7 (35%) pts remained on treatment. Treatment-related AEs (TRAEs, any grade/grade ≥3) were reported in 70%/5% of pts. The most common TRAEs were diarrhea (9 pts [45%], all grade 1), rash (3 pts [15%], all grade 1), anemia (2 pts [10%], all grade 2), and increased AST (2 pts [10%], all grade 2). Only one pt had a grade ≥3 TRAE (grade 3 increased lipase). No grade 4 or 5 AEs were reported. Conclusions: Pooled analysis of HER2-positive CRC pts from two clinical trials indicates that zongertinib monotherapy has encouraging clinical activity and manageable safety in pts with advanced, HER2-positive CRC, supported by PDX models. Based on these findings, zongertinib continues to be developed in CRC, with Beamion PANTUMOR-1 actively enrolling. An additional Phase Ib/II trial (Beamion BCGC-1, NCT06324357) is also underway. Clinical trial information: NCT04886804 , NCT06581432 .

Lorlatinib vs crizotinib as first-line treatment for advanced <i>ALK</i> + non-small cell lung cancer: 7-year update from the phase 3 CROWN study.

8502 Background: Median progression-free survival (PFS) was not reached (NR) with lorlatinib in the phase 3 CROWN study after 5 yrs of f/u, representing the longest PFS reported in advanced non-small cell lung cancer (NSCLC). Due to the unprecedented PFS benefit with lorlatinib after 5 yrs of f/u and the decreased event rate after the first 24 mos in the study, we aimed to quantify long-term outcomes at 7 yrs. Methods: 296 treatment-naive patients (pts) with advanced ALK + NSCLC were randomized 1:1 to receive lorlatinib 100 mg once daily (n=149) or crizotinib 250 mg twice daily (n=147). This post hoc analysis presents investigator-assessed efficacy outcomes, safety, and biomarker analyses. Formal statistical testing between arms was not performed. Results: As of October 31, 2025, 66 of 149 pts (44%) vs 4 of 142 (3%) were receiving lorlatinib vs crizotinib. With a median f/u for PFS (95% CI) of 83.0 (81.2-86.3) and 77.2 mos (36.8-not evaluable), respectively, median PFS (95% CI) was NR (68.5-NR) with lorlatinib and 9.1 mos (7.4-10.9) with crizotinib (HR, 0.19; 95% CI, 0.13-0.26); the 7-yr PFS (95% CI) was 55% (46-63) and 3% (1-8). In the lorlatinib arm, pts without a PFS event at the end of 24 mos had a 79% probability of survival without progression at yr 7. PFS benefit was consistent across all prespecified subgroups. No new intracranial (IC) progression events occurred after the first 30 mos on lorlatinib. Median time to IC progression (95% CI) was NR (NR-NR) with lorlatinib and 16.4 mos (12.7-21.9) with crizotinib (HR, 0.06; 95% CI, 0.03-0.12). The number of overall survival (OS) events for a protocol-specified analysis has not been met; OS f/u is still ongoing. The safety profile was consistent with the 5-yr results, with all-cause grade 3/4 adverse events (AEs) in 77% of pts with lorlatinib and 57% with crizotinib. Treatment-related AEs (TRAEs) led to permanent treatment discontinuation in 5% of pts with lorlatinib and 6% with crizotinib. No new permanent discontinuations due to TRAEs occurred after the first 26 mos with lorlatinib. Dose reductions were reported in 34% of pts in the lorlatinib arm (17% had 1 dose reduction and 17% had 2 reductions). Long-term efficacy was similar between pts with and without dose reduction. Exploratory translational analyses of outcomes in pts with different molecular subtypes and resistance mechanisms at the end of treatment are ongoing. Conclusions: With median PFS yet to be reached after 7 yrs of f/u in CROWN, lorlatinib continues to show unprecedented and highly durable benefit in treatment-naïve pts with advanced ALK + NSCLC. In pts without a PFS event at 24 mos, the probability of survival without progressive disease at 7 yrs was 79%. Longer f/u showed very few additional PFS events, no new IC progression, and no new treatment-related discontinuation, suggesting long-term substantial benefit with lorlatinib for the majority of pts with advanced ALK + NSCLC. Clinical trial information: NCT03052608 .

A prospective study of tumor-informed ctDNA minimal residual disease detection in bone and soft tissue sarcomas.

3057 Background: The high recurrence and metastasis rates lead to poor survival of patients with sarcoma. Conventional imaging often detects relapse at a relatively late stage. In our previous study, circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) detection demonstrated strong prognostic value in osteosarcoma, enabling earlier detection of recurrence compared with radiographic surveillance. However, whether this approach is applicable to soft tissue sarcomas and the broader sarcoma population remains unclear. Methods: Between August 2020 and March 2024, patients with sarcoma were prospectively enrolled at a single center. Tumor-informed MRD assays were designed using whole-exome sequencing of paired tumor–normal samples. Longitudinal postoperative plasma samples were collected for ctDNA analysis. Survival outcomes were assessed using Kaplan–Meier analysis with log-rank tests. Multivariable Cox proportional hazards regression was performed adjusting for age, sex, tumor necrosis score, and histologic subtype (osteosarcoma vs non-osteosarcoma). Results: A total of 121 patients were included, comprising 74 bone-origin sarcomas (72 osteosarcomas) and 47 soft tissue sarcomas; 77 patients were male and 44 were female. With a median follow-up of 21.7 months, postoperative ctDNA positivity was strongly associated with inferior survival. Median relapse-free survival was 6 months in ctDNA-positive patients versus 43 months in ctDNA-negative patients (P &lt; 0.001). This prognostic separation remained significant across early (≤1 month), intermediate (1–6 months), and late (&gt;6 months) postoperative time windows. In multivariable Cox analysis, postoperative ctDNA status remained an independent prognostic factor (HR = 5.20, 95% CI: 2.07–13.08; P &lt; 0.001). In 19 patients, ctDNA positivity preceded radiographic evidence of recurrence, with a mean lead time of approximately 3 months. Notably, 56 patients with persistently negative postoperative ctDNA experienced no recurrence or metastasis during follow-up. Conclusions: Tumor-informed ctDNA-based MRD detection is applicable to a broad range of sarcoma subtypes and provides robust prognostic information following surgery. These findings support the role of ctDNA as an early biomarker for disease recurrence in sarcoma. Clinical trial information: ChiCTR2400083045.

A phase III randomized study comparing BCD-201, a pembrolizumab biosimilar candidate, and reference pembrolizumab in patients with advanced melanoma.

9541 Background: The development of clinically comparable biosimilars of key immuno-oncology agents is essential to improving global access to effective therapy. BCD-201 is a proposed pembrolizumab biosimilar that has shown high analytical similarity in preclinical studies, and pharmacokinetic equivalence to the reference pembrolizumab in phase I study (NCT05739006).This phase III trial evaluated the clinical equivalence of BCD-201 versus reference pembrolizumab in patients with advanced melanoma. Methods: This international, multicenter, randomized, double-blind phase III study enrolled adult patients with unresectable or metastatic cutaneous melanoma. Patients were randomized 1:1 to receive BCD-201 or reference pembrolizumab 200 mg IV every 3 weeks for 24 weeks. Randomization was stratified by ECOG (0 vs 1), PD-L1 expression (&lt;5% vs ≥5%), and disease stage (AJCC 7th edition M0/M1a/M1b vs M1c). The primary endpoint was objective response rate (ORR) per RECIST v1.1 assessed by blinded independent central review (BICR) at week 24 in the ITT population. Equivalence was concluded if the 95% confidence interval (CI) for the ORR difference fell within prespecified margins of −15% to +15%. Secondary efficacy endpoints included ORR per iRECIST, progression-free survival (PFS), overall survival (OS). Results: A total of 479 patients were included in the ITT population (BCD-201, n=234; reference pembrolizumab, n=245), with balanced baseline characteristics. At week 24, ORR was 33.3% in the BCD-201 group and 32.7% in the reference pembrolizumab group in ITT population. The unstratified ORR difference was 0.7% (95% CI −7.7 to 9.1), fully within the prespecified equivalence margins. Results were consistent across per-protocol and stratified sensitivity analyses. Secondary efficacy endpoints, including ORR per iRECIST, OS, and DOR, were comparable between groups. At 24 weeks, PFS rates were 51.9% for BCD-201 and 50.5% for reference pembrolizumab per RECIST 1.1. OS rate at 24 week was 90.2% in the BCD-201 group and 89.3% in the reference pembrolizumab group. Longer-term efficacy and safety data will be reported in future analyses. Safety profiles were similar between groups, with grade ≥3 AEs reported in 19.7% and 21.9% of patients for BCD-201 and reference pembrolizumab. Main PK parameters (AUC and C max ) met equivalence criteria. Immunogenicity was low and comparable between groups, with binding antibodies (Abs) detected in 7 (3.1%) and 6 (2.6%) patients in the BCD-201 and comparator groups, respectively. No neutralizing Abs were detected. Conclusions: BCD-201 demonstrated equivalent efficacy to reference pembrolizumab with comparable safety, pharmacokinetics, and immunogenicity in patients with advanced melanoma. These data support BCD-201 as a pembrolizumab biosimilar and highlight its potential to expand access to anti-PD-1 therapy. Clinical trial information: NCT05986331 .

Social determinants of health (SDOH) and barriers to allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) in a community setting.

e13519 Background: HCT is curative for patients with intermediate- or adverse-risk AML; however, timely referral to transplant centers is often delayed or absent, particularly in underserved populations. In Brooklyn, NY, where approximately 39% of residents are immigrants, patients face unique challenges related to language, insurance, and other social determinants of health (SDOH). We examined patient-, provider-, and institutional-level barriers contributing to delayed or absent access to HCT in a community-based hospital affiliated with a major academic center. Methods: We conducted an IRB-approved retrospective study of adults aged 18 to 79 diagnosed with AML at NewYork-Presbyterian Brooklyn Methodist Hospital (12/2021 – 1/2026), including those referred for HCT at affiliated Weill Cornell Medicine transplant program. Data were extracted from the medical record and BMT registry. The primary outcome was the proportion of HCT-indicated patients, per ELN 2022 criteria, who received a transplant consultation. Secondary outcomes included time from AML diagnosis to HCT consultation, time to HCT, and identification of barriers to transplantation. Results: Twenty patients were identified; 18 (90%) were racial or ethnic minorities (12 Black, 3 Asian, 2 Hispanic, 1 Mediterranean), and 25% required interpreter services. Six patients had favorable-risk disease, while 14 (70%), all non-White, met intermediate- or adverse-risk criteria. Among these, only six (43%) underwent HCT consultation, and all six proceeded to transplantation (4 in CR1 or CRi, 2 in CR2 or greater). Median time from AML diagnosis to HCT consultation was 66 days (range, 30 to 280), and median time to HCT was 154 days (range, 102 to 645). Among transplanted patients, infectious complications (67%), insurance-related delays (33%), and lack of a caregiver (17%) were the most common contributors to prolonged timelines. The median age of transplanted patients was 43 years (range, 31 to 58) compared with 75 years (range, 63 to 79) among non-transplanted patients. Among non-referred patients, 7 of 8 (88%) were aged 71 to 79; one declined, and one had significant comorbidities. Conclusions: While patient-level, structural barriers, and other SDOH significantly affect timely access to HCT, age-related referral patterns emerged as a key and potentially modifiable determinant of transplant evaluation. The marked age disparity between referred and non-referred patients underscores the importance of early, objective HCT assessment informed by contemporary transplant eligibility, including the feasibility of HCT in selected patients over age 70. Strengthening partnerships between community oncology practices and transplant centers through standardized referral pathways and shared decision-making may mitigate subjective biases and improve access to curative therapies.

Pathologic nodal burden in TAILOR-RT–eligible breast cancer: An NCDB analysis informing regional therapy de-escalation.

e12616 Background: The optimal extent of axillary management in patients with biologically low-risk, node-positive breast cancer remains uncertain. While OncotypeDX has refined systemic therapy decision-making in estrogen receptor(ER)–positive, HER2-negative disease, its role in guiding locoregional treatment de-escalation is less well-defined. The ongoing TAILOR-RT trial aims to clarify whether regional nodal irradiation (RT) can be safely omitted in select low-risk patients with limited nodal disease. Using a national database, we evaluated the extent of pathologic nodal burden and the association between regional radiotherapy and overall survival in this population with biologically favorable disease and limited nodal burden. Methods: Using the National Cancer Database (NCDB), women age≥40Y with ER+HER2− breast cancer with OncotypeDX Score&lt;18 were identified. Consistent with TAILOR-RT eligibility, the cohort was defined by limited nodal disease (cN1). First, to assess the possibility of greater extent of pathologic nodal burden, we limited our population to only those patients who underwent upfront axillary lymph node dissection (ALND) or initial sentinel lymph node biopsy (SLNB) converted to ALND. Secondarily, we performed a Kaplan-Meier analysis of all patients meeting the above inclusion criteria, who underwent SLNB or ALND, to determine the impact of adjuvant radiotherapy on overall survival in this low-risk population. Results: In total, 3,646 patients met inclusion criteria who had ALND, with 2,745 (75%) having invasive ductal carcinoma and 788 (22%) lobular histology. Median age was 63 years (IQR 54–70). Median lymph nodes examined was 12 (IQR 8–17), with a median of 2 positive nodes (IQR 1–3). On final pathology, 814 patients (22%) had &gt;3 positive nodes, suggesting higher nodal burden than previously estimated. Next, 5101 patients were identified who underwent SLNB or ALND, and had documented receipt (2574, 50.5%) or omission (2527, 49.5%) of regional nodal therapy. Following SLNB and ALND, respectively, 54% (1130/2090) and 48% (1444/3011) received regional radiation. Due to the possibility of selection bias prompting either SLNB or ALND, survival between these groups was analyzed separately to assess the impact of regional radiotherapy, which did not differ (ALND 5YS: NoRT 91.7% vs. RT 93.2% &amp; SLNB 5YS: NoRT 94.7% vs RT 93.1%, p =0.12). Conclusions: While we acknowledge NCDB limitations, including inability to assess breast surgery type, receipt of endocrine therapy, or recurrence, we provide reassuring evidence that most patients meeting TAILOR-RT eligibility did not have markedly higher nodal burden on final pathology. Furthermore, this population may have been adequately treated with axillary surgery alone, without regional radiotherapy. Pending prospective findings, our report further supports axillary therapy de-escalation to reduce morbidity.

Association between tumor mutation status, pretreatment weight change, and overall survival in metastatic non–small cell lung cancer.

e24075 Background: Unintentional weight loss is common in non–small cell lung cancer (NSCLC) and has been correlated with poor outcomes. Additionally, tumor mutations may be associated with distinct metabolic changes. This study aimed to evaluate the association between tumor mutation status and pretreatment weight loss (WL) or weight gain (WG) in metastatic NSCLC. Additionally, the relationship between these weight changes and OS after treatment was examined. Methods: This is a retrospective (Jan 2017-Dec 2023) observational study of adults with new diagnosis Stage IV NSCLC treated at Atrium Health Levine Cancer (AHLC). Eligible patients had at least two recorded weight measurements, including a baseline weight and a follow-up weight measured closest to day 30 after diagnosis (±14 days). Patients with molecular testing (EGFR, ALK, ROS1, BRAF, KRAS) were identified. A Univariable and multivariable ordinal logistic regression were used to model tumor mutation status and impact on pretreatment weight changes. This was categorized into 3 groups: 1) WG/Stable, 2) WL &lt;3%, and 3) WL ≥3%. OS was evaluated using direct adjustment methods. P&lt;0.05 was statistically significant. Results are summarized by descriptive statistics, association level and survival analysis. Results: 264 patients were eligible. 218 patients had molecular testing results, (96/218) had a tumor mutation. Median age was 68 y/o; 48.6% female and 73.9% White. Demographic and clinical characteristics were similar between groups. However, the mutation group had higher proportion of females and current smokers. In multivariable models adjusting for age, sex, race, smoking status, obesity (BMI ≥30) Charlson Comorbidity Index, number of metastases and income/education, we found no significant association between pretreatment weight change and tumor mutation status. For the entire cohort (N=264), median OS from diagnosis was 22 (.43-.55) months. There was significant difference in OS between patients in different weight change groups (p=.042). Patients WG/Stable had the longest survival of 28 months (.41-.58) compared to those with ≥3% WL [18 (.38-.58) months, p=0.012], or &lt;3% WL [22 (.41-.61) months, p=0.4]. Conclusions: Pre-treatment weight loss is an important prognostic indicator in metastatic NSCLC. A detailed weight history before treatment can help identify patients at high risk for early mortality and guide timely nutrition interventions. Pretreatment weight change and overall survival. Survival N 20 Months 40 Months 60 Months 80 Months Median, months # Deaths (%) Overall 264 53% (.48-.60) 34% (.28-.40) 21% (.14-.33) 14% (.07-.28) 22 159 (60%) Weight Change WG/Stable 109 60% (.52-.68) 40% (.32-.50) 26% (.17-.41) 18% (.09-.36) 28 64 (59%) &lt;3% WL 80 55% (.46-.65) 35% (.26-.47) 22% (.12-.38) 14% (.06-.32) 22 48 (60%) ≥3% WL 75 44% (.35-.56) 24% (.17-.36) 13% (.06-.28) 8% (.03-.22) 18 47 (63%)

Comparison of cisplatin/gemcitabine or carboplatin/gemcitabine on efficacy, toxicity, and quality of life from the randomized DISCUS trial.

4583 Background: The DISCUS trial compared 3 versus 6 cycles (3C versus 6C) of chemotherapy followed by avelumab in 267 patients receiving first-line treatment for metastatic urothelial cancer. It showed 3 cycles of chemotherapy followed by maintenance avelumab was associated with better QoL than six cycles (NCT06892860). Efficacy outcomes of the two arms appeared similar. Here we compare the cisplatin (cis) or carboplatin (carbo) chemotherapy subsets in the 3C and 6C arms. Methods: Patients were randomized to receive either 3 or 6 cycles of chemotherapy. Cisplatin or carboplatin was allocated by physician choice. Progression free survival (PFS), Overall survival (OS), response rates, patient-reported outcomes (PROs) and treatment related adverse events were collected (TRAEs) were collected. The analysis was exploratory and p values nominal. Results: 267 were included of whom 55 received 3C/cis, 55 6C/cis, 78 3C/carbo and 79 6C/carbo. Patients receiving carboplatin had poor performance status (ECOG &gt;=1 in 17% cis vs 35% carbo). Table 1 showed similar efficacy outcomes with potentially marginally superior OS with cisplatin. The comparison of efficacy and QOL endpoints for 3 vs 6 cycles of carboplatin showed many similarities. Six cycles of cisplatin-based chemotherapy was associated with a major drop in QOL compared to 3 cycles without showing any clear benefits in efficacy endpoints. Conclusions: The QoL benefits of shorter chemotherapy appear to be more marked in patients receiving cisplatin than carboplatin. The efficacy results for 3 cycles of cisplatin were impressive. This study was not powered for non-inferiority. Clinical trial information: NCT06892860 . Outcomes by treatment arm. 3C/cis (n=56) 3C/carbo (n=77) 6C/cis (n=54) 6C/carbo(n=80) CR (%) 16% 10% 14% 12% PFS (months), median(95% CI) 8.8(6.5-12.8) 8.0(5.8-12.0) 8.7(6.4-18.9) 9.0(6.6-13.1) OS (months), median(95% CI) Not reached(12.8-.) 18.5(12.6-.) 21.9(10.5-.) 15.0(9.8-.) G3 and above TRAE (n) 32 40 49 79 PRO (change from baseline to C7D1) 2.96 -2.51 -13.44 -4.86

Sintilimab combined with short-course intensified chemotherapy regimen nab-POF in the treatment of metastatic gastric cancer (FDZL-GC002): A single-arm, phase 2 trial.

4057 Background: This prospective phase II study investigates a novel therapeutic strategy combining PD-1 inhibitor sintilimab (Sin) with short-course intensified chemotherapy regimen Nab-POF as first-line treatment for metastatic gastric cancer (MGC), based on the hypothesis that short-duration, high-intensity chemotherapy may potentiate antitumor immunity while reducing the cumulative immunosuppressive burden of prolonged chemotherapy. Methods: Eligible patients (pts) received Sin (200mg IV), nab-paclitaxel (125mg/m²), oxaliplatin (85mg/m²), and fluorouracil (2400mg/m² as a 48-hour infusion) (plus trastuzumab for HER2+ pts) Q2W. After 6 cycles, pts without disease progression received maintenance treatment (capecitabine + Sin). Upon disease progression, HER2- pts underwent reinduction with the Nab-POF regimen ± Sin, for up to 6 cycles, followed by maintenance therapy (S-1 +/- Sin). Tumor response was assessed every 3 cycles. PFS1 was defined as the time from informed consent to first progression. PFS2 was defined as the time from consent to second progression. If reinduction therapy was not performed, PFS2 equals to PFS1. The primary endpoint was PFS2 in HER2- pts. Results: In total, 123 pts were enrolled up to 09/2025. 118 pts were evaluable. This report presents the results for the HER2- population. Among 90 HER2- pts, the median age was 60 (23-83), with 72.2% male. The common metastatic sites included the liver (36.7%), peritoneum (26.7%), bone (13.3%), and lungs (6.7%). ORR was 82.2% (74/90) and DCR was 100%. Nine pts received complete response and CR rate was 10.0%. 2-year DFS and OS rate were both 100% among pts with CR. 60 pts progressed and 47 patients died. 25 pts experienced reinduction with the Nab-POF regimen ± Sin. Median PFS1 was 13.6mo (95%CI 9.8-16.1) and median PFS2 was 16.2mo (95%CI 11.0-23.2). Median OS was 21.3mo (95%CI 11.3-NR). 1-year OS rate was 72.2% (95%CI 63.5-82.1) and 2-year OS rate was 44.2% (95%CI 33.9-57.6). Subgroup analysis showed whether signet ring cells are present or not, whether liver metastasis occurs or not, and the level of CPS were not related to the therapeutic effect. All pts experienced treatment-related adverse events (AEs). Grade 3/4 AEs were 55.6% (50/90) and neutrophil decrease was the most common at 36.7% (33/90). Immune-related AEs occurred in 22(24.4%) pts, including 6 (6.7%) grade 3/4 events, which were effectively controlled. Conclusions: Sin plus short-course intensified chemotherapy regimen Nab-POF demonstrates high response and CR rate, and remarkable long-term effects. This approach may represent a feasible first-line treatment strategy, warranting further evaluation in randomized trials. Clinical trial information: NCT05982301 .

Proteolysis-targeting chimera (PROTAC) targeting BTK degradation for cancer therapy in mantle cell lymphoma.

e19045 Background: Mantle cell lymphoma (MCL) is characterized by Bruton tyrosine kinase (BTK)-signaling which activates the B-cell receptor (BCR) signaling cascade. Although BTK-inhibitors are effective therapy, acquired resistance is common. Proteolysis-targeting chimera molecules (PROTACs) facilitating BTK-degradation (BTK-PROTAC) are a potential therapy. Methods: We designed 24 BTK-PROTACs and screened their activity against MCL cell lines through half maximal inhibitory concentration (IC50) assays and BTK-degradation efficiency. Effects of BTK-PROTAC on differentially expressed genes and on activation of the BCR-signaling cascade were studied by RNA-seq and molecular experiments. BTK variant cells were developed to assess the ability of BTK-PROTAC to reverse acquired BTK-inhibitor resistance in vitro assays and in mouse models. Results: Amongst BTK-PROTACs we synthesized C23 had the strongest ability to degrade BTK and inhibit proliferation of several MCL cell lines. C23 induced cell apoptosis and suppressed cancer growth by activating the ubiquitin-proteasome pathway thereby inhibiting the BCR-signaling cascade including NF-κB- and PI3K-AKT-mTOR-signaling. C23 degraded BTK inhibiting growth of BTK C481S and BTK L528W variant cells and suppressed growth of MCL cells in mouse xenograft models with BTK C481S and BTK L528W variants. Conclusions: The C23 BTK-PROTAC inhibits MCL cells with BTK variants resistant to BTK-inhibitors in vitro and in vivo models. BTK-PROTAC C23 is a potential therapy of BTK-inhibitor resistant MCL.

Exploratory analysis of prognostic value of ctDNA monitoring among advanced breast cancer with oligometastatic disease: An ancillary biomarker study of JCOG 2110 (JCOG2110A1).

TPS1158 Background: Oligometastatic advanced breast cancer represents a biologically heterogeneous disease state in which a subset of patients may achieve prolonged disease control or potential cure through the addition of definitive local therapy to systemic treatment. However, conventional imaging has limited sensitivity for detecting minimal residual disease (MRD), and reliable biomarkers to identify patients most likely to benefit from local therapy remain lacking. Circulating tumor DNA (ctDNA) has emerged as a sensitive, minimally invasive marker of tumor burden and treatment response and may provide complementary information beyond radiographic assessment. JCOG2110 is a phase III randomized trial evaluating whether the addition of definitive local therapy (surgery or radiotherapy to all detectable lesions) to systemic therapy improves survival in patients with advanced breast cancer with three or fewer oligometastatic lesions. JCOG2110A1 is an ancillary biomarker study designed to characterize ctDNA dynamics in this clinical setting and to explore the clinical significance of ctDNA-based MRD assessment. Methods: Eligible patients are those enrolled in JCOG2110 who provide written informed consent prior to initiation of protocol-defined systemic therapy. Plasma ctDNA will be analyzed using Guardant Reveal, a next-generation sequencing–based assay integrating genomic alterations and methylation signatures, and reported as ctDNA positive or negative with quantitative estimates of tumor fraction. Blood samples will be collected longitudinally at predefined timepoints: before systemic therapy, prior to completion of the initial 12-week systemic treatment, and during protocol-specified follow-up aligned with imaging assessments after second registration. In cases of disease progression, ctDNA will be collected at progression and subsequent sampling will be discontinued. The primary endpoint is the proportion of ctDNA clearance and ctDNA level reduction after initial systemic therapy among patients who are ctDNA-positive at baseline. Secondary endpoints include ctDNA positivity at each timepoint, associations between ctDNA kinetics and radiographic tumor prognosis, and correlations with clinical characteristics such as tumor subtype, number of metastatic lesions, and treatment allocation. This study aims to define the detectability and early kinetics of ctDNA in oligometastatic advanced breast cancer and to generate prospective evidence regarding the prognostic and potential predictive value of ctDNA for treatment outcomes and benefit from local therapy. Clinical trial information: jRCTs031230439.