Browse Articles
Discover research articles across all indexed journals
Performance of a multi-cancer early detection test (MCED) for detecting small hepatocellular carcinoma (HCC) in a screening population.
4168 Background: Early diagnosis of small HCC (defined as single nodule ≤ 3 cm) is crucial, as it represents the optimal window for curative treatments. Abdominal ultrasound with alpha-fetoprotein (AFP) is recommended for HCC surveillance in high-risk population. However, traditional modality detects only ~63% of small HCC, resulting in most HCC being diagnosed at advanced stages. Genie-Seq, a cfDNA-based MCED assay, covers 5 high-mortality cancers including HCC. Here, we report preliminary results evaluating the performance of Genie-Seq for small HCC in an asymptomatic screening population. Methods: Participants aged 40-74 years with no clinical suspicion of cancer were enrolled in a prospective, interventional study. All participants underwent Genie-Seq testing and standard-of-care (SOC) screenings according to the China Guidelines for Cancer Screening, including abdominal ultrasound and AFP. Genie-Seq detects cancer signals and localizes tissue-of-origin (TOO) simultaneously. Further HCC-focused diagnostic workup was performed per physician's discretion if: 1) suspicious findings on HCC screening, or 2) positive MCED results with liver as the top-predicted TOO. Diagnostic outcomes were reviewed for cancer status, TOO prediction accuracy, and stage. Results: As of December 2025, 1210 participants completed MCED testing and HCC screening. Nine participants were suspected of HCC and underwent further evaluation, with definitive diagnosis achieved in 7. Of these, 4 were confirmed as HCC (3 small HCCs, 1 stage II), 1 had synchronous gastric and colorectal cancers, and 2 had benign hepatic lesions. Genie-Seq identified all HCC cases with 100% TOO prediction accuracy, including 2 that were missed or initially misdiagnosed by traditional imaging. Patient 885 was exclusively identified by MCED, as no nodule was detected by ultrasound. Patient 888 had atypical features on contrast-enhanced CT/Gd-EOB-DTPA MRI (initial suspicion of inflammatory pseudotumor), and Genie-Seq positivity prompted contrast-enhanced ultrasound, leading to definitive diagnosis of small HCC. Conclusions: Genie-Seq exhibits excellent performance for small HCC detection in screening population, supporting it as a complementary tool to conventional preventive care and potentially improving curable HCC detection. Diagnostic outcomes of participants achieved diagnostic resolution. Participants Suspicious Lesions Detected by Ultrasound AFP (ng/ml) [1] MCED Results Diagnosis Tumor Stage (AJCC) 0108 Yes 2.96 Negative Hepatic cysts 0572 Yes 4.25 Negative Hepatic cavernous hemangioma 0640 No 2.6 Positive Multiple primary cancers Gastric cancer: IIB Colorectal cancer: I 0723 Yes 58.55 Positive HCC II 0885 No 8.16 Positive HCC IA 0888 Yes 42.53 Positive HCC IB 0971 Yes 9.11 Positive HCC IA [1] AFP levels of < 7 ng/mL were defined as normal.
Efficacy, safety, and genetic analysis of orelabrutinib combined with rituximab as first-line systemic treatment for marginal zone lymphoma.
7059 Background: Marginal zone lymphoma (MZL) is a heterogeneous B-cell malignancy that is often managed with chemoimmunotherapy in the first-line setting, but chemotherapy entails considerable toxicity. Orelabrutinib, a novel oral BTK inhibitor which offers improved target selectivity and fewer off-target effects. This study evaluates the chemo-free combination of orelabrutinib plus rituximab in untreated MZL. Methods: This is a prospective, single-arm, multicenter phase II clinical trial (NCT07022223). Patients with untreated MZL who met ECOG criteria of 0–2 and were in need of treatment, or who had failed local, were eligible. All participants will receive induction therapy with the orelabrutinib and rituximab regimen. The treatment cycle is 28 days, with a total of 4~6 cycles. The induction treatment period is as follows: Cycle 1: Rituximab, 375 mg/m², on day 1. Cycles 2-6: Orelabrutinib, 150 mg, once daily orally, from day 1-28, plus rituximab 375 mg/m² on day 1. Patients who achieve a partial response (PR) or better will enter a 2-year maintenance period with orelabrutinib. The primary endpoint is the overall response rate (ORR). Secondary endpoints include complete response (CR) rate, PR rate, progression-free survival (PFS), and overall survival (OS). Safety is assessed by monitoring adverse events (AEs). Results: From March 2025 to December 2025, a total of 40 patients with MZL (32 MALT, 6 NMZL, 2 SMZL) were enrolled. The median age at diagnosis was 68 years (range 44–84), and 82.5 % of patients were older than 60 years. 21 (52.5%) were female. Most patients had an ECOG score of 0-1 (28/40), Ann Arbor Stage Ⅲ-IV disease (35/40). Twelve patients had an MZL-International Prognostic Index score of ≥2. Thirteen patients had failed prior local therapy, the majority of whom had undergone surgical resection. After three cycles, 25 patients were evaluable, with an ORR of 80 % (20/25) and a CRR of 24 %. Following six cycles, 13 patients were evaluable, achieving an ORR of 100 % (13/13) and a CRR of 62 % (8/13). The median time to response was 72 days. With a median follow-up of 5.7 months (range, 5.1-6.8), the median PFS and OS were not reached, the 1-year PFS rates were 97.2% and the 1-year OS rates were 100%. Next-generation sequencing (NGS) was performed on 16 patients, a total of 158 mutated genes were identified, with missense mutations predominating (62.7%). The most frequently mutated genes were NOTCH2, FAT4, LRP1B, PCLO, and SYNE1, all at 31.2 %. Treatment was generally well tolerated, only 13 patients experienced adverse events, the most common adverse events were anemia (15 %), infection (12.5 %) and neutropenia (10 %). Notably, BTK inhibitor–associated atrial fibrillation (0 %) and bradycardia (0 %) were absent. Conclusions: The combination of orelaburtinib and rituximab shows significant activity in MZL, with a manageable toxicity profile. Clinical trial information: NCT07022223 .
The great mismatch: Assessing cancer clinical trial accrual rates.
e23151 Background: Efforts to increase cancer clinical trial accruals have been disappointing. Much focus has been placed on patient and some system barriers. Yet, pinpointing the causes of low accrual rates is needed to more effectively increase accruals. We undertook this study to identify the sites and breadth of low accrual rates to cancer clinical trials. Methods: At 3 participating Cancer Centers, we identified breast, liver and lung cancer patients at treatment decision points, when clinical trials would likely be more relevant. We included all open medical treatment trials for these cancers at these sites. Regular Expressions and Python algorithms identified patients with upcoming appointments to determine those at treatment decision points. Both trials and patients were classified by cancer type, stage, receptor and biomarker status. We then matched patients and trials and informed oncologists and patients about the match lists. Results: Of 63,255 patients with breast, liver or lung cancer and an appointment in the upcoming week, 11,502 were found to be at a treatment decision point (e.g., new, recurrent or progressing cancer) via SQL and 1552 via additional Python/RegEx algorithms. Of these,523 were consented and 326 matched to trials at a high level (e.g., type, stage, receptors). Subsequent manual review found 147 to be potentially eligible for an open trial. Of these, 39 enrolled in a CT. Among patients, 67% of breast, 11% of liver and 18% of lung, were early stage. Open trials for early-stage cancers across the 3 sites included: 50% of breast; 26% of liver and 26% of lung. Overall 51% of cancer patients had early stage while 28% of trials targeted early-stage cancer. Conclusions: There is a significant mismatch between the stages of cancer with which patients present, and the stages of cancer targeted for clinical trials. Clinical trial information: NCT05146297 .
Clinical and molecular features of patients with <i>PIK3CA</i> -mutant ( <i>PIK3CA</i> m) ER+/HER2− breast cancer with detectable circulating tumor DNA (ctDNA) in early breast cancer (eBC).
e12609 Background: We previously reported that ~35% of ER+/HER2- eBC patients with a ctDNA-positive (ctDNA+) test result after surgery had a PIK3CA m primary tumor. Of patients with +ctDNA testing, those with PIK3CA m eBC had worse outcomes (versus PIK3CA -wild type) 1 . However, the impact of ctDNA dynamics during treatment of PIK3CA m eBC remains understudied. Methods: We conducted a retrospective analysis of patients at our institution with ER+/HER2- breast cancer (BC) who had >1 ctDNA+ test result via a personalized, tumor-informed 16-plex mPCR-NGS ctDNA assay (Signatera, Natera, Inc.). PIK3CA m status was determined by analysis of the Signatera whole exome sequencing data. Clinical data were obtained by review of electronic medical records. Results: 41 patients with ER+/HER2- BC and tumor PIK3CA m with >1 ctDNA+ test were identified. 35/41 (85.4%) patients had eBC at time of initial diagnosis; 16/35 (45.7%) of these had a positive ctDNA test in the adjuvant treatment (AT) setting. Median follow up for this cohort is 61.5 months. Among eBC patients that were ctDNA+ in the AT setting, 7/16 (43.8%) patients received chemotherapy, 12/16 (75.0%) received adjuvant endocrine therapy, and 3/16 (18.8%) received adjuvant CDK4/6 inhibitor therapy. The median time from surgery to first ctDNA test for these patients in the AT setting was 15.4 months. The initial ctDNA test was positive for 11/16 (68.8%) patients; 5/16 (31.3%) had a negative initial ctDNA test and later had a ctDNA+ test. 5/16 (31.3%) patients had clearance in the AT setting. 3/5 (60.0%) cleared ctDNA on adjuvant endocrine therapy +/- CDK4/6i and 2/5 (40.0%) cleared ctDNA in the absence of therapy. None of the 5 patients with ctDNA clearance have had distant metastatic recurrence with a median follow up after +ctDNA test of 15.8 months. Median time from first ctDNA+ test to ctDNA clearance was 57 days in the AT setting. 11/16 (68.8%) did not clear ctDNA; 7/11 (63.6%) of these patients had a distant recurrence and 1/11 (9.1%) had a local recurrence. 3/11 (27.3%) did not have recurrence, with a median follow up after first ctDNA+ test of 14.4 months. Of patients with distant metastatic recurrence, the median time from first ctDNA+ to distant recurrence was 6.0 months. Conclusions: This analysis explores ctDNA dynamics and clinical features during treatment for eBC in patients with +ctDNA and tumor PIK3CA mutations. These data indicate that ctDNA clearance is associated with better prognosis even in this high-risk population of patients with PIK3CA m tumors and +ctDNA testing. These data may inform further research and practice in treating ER+/HER2- PIK3CA m early breast cancers. Reference: 1 Lipsyc-Sharf et al. SABCS 2024, PS9-01; https://doi.org/10.1158/1557-3265.SABCS24-PS9-01
First disclosure of frontline treatment (1L tx) with the selective CDK4 inhibitor BGB-43395 in combination with letrozole for metastatic HR+/HER2− breast cancer (BC): A phase 1 safety expansion.
1066 Background: BGB-43395, a highly selective CDK4i, showed preclinical antitumor activity characterized by improved CDK4 target coverage and selectivity over CDK6. This enhanced selectivity may reduce off-target toxicity and the need for tx modifications. BGB-43395 is being evaluated as monotherapy or with endocrine therapy in patients (pts) with HR+/HER2− BC and other advanced solid tumors in an ongoing phase 1a/1b open-label, international study (NCT06120283). We report on the safety, preliminary anti-tumor activity, and pharmacodynamics (PD) of BGB-43395 + letrozole as 1L tx for BC. Methods: In safety expansion cohort 2, CDK4/6i-naive pts with advanced/metastatic HR+/HER2− BC were randomized to receive BGB-43395 240, 400, or 600 mg PO BID + letrozole to determine the recommended dose for further development. The objectives were to assess safety, preliminary anti-tumor activity, and PD. Results: As of Nov 11, 2025, 58 pts received study tx (240 mg n = 19; 400 mg n = 19; 600 mg n = 20). Treatment emergent adverse events (TEAEs) occurred in 98% of pts; grade (G)≥3 TEAEs in 32%, 37%, and 65% of pts on 240 mg, 400 mg, and 600 mg, respectively. The most common TEAEs (mostly G1/2) were (240 mg / 400 mg / 600 mg): diarrhea (79% / 95% / 90% [G3 5% / 11% / 30%]), nausea (53% / 68% / 85% [G3 0% / 5% / 0%]), and vomiting (26% / 47% / 60% [G3 0% / 0% / 0%]). Rates of TEAE hematologic toxicities (mostly G1/2) were low; neutrophil count decreased/neutropenia (240 mg 26% [G3 0%]; 400 mg 21% [G3 0%]; 600 mg 20% [G3 10%]); anemia (240 mg 5% [G3 0%]; 400 mg 21% [G3 0%]; 600 mg 20% [G3 5%]); platelet count decreased/thrombocytopenia ([all G1 or 2] 240 mg 5%; 400 mg 0%; 600 mg 5%). TEAEs led to dose modification in 53% of pts (median relative dose intensity: 240 mg 100%; 400 mg 97%; 600 mg 69%), tx discontinuation in 3% (240 mg, 1 pt; 600 mg, 1 pt), and 0 deaths. BGB-43395 + letrozole demonstrated early efficacy (Table) and strong PD effects, indicated by TK1 reduction and ctDNA decrease. Median study follow-up was 6.8 (range 3.2-9.7) mo, median time-to-response was 3.6 (range 1.6-8.4) mo, and median PFS was not reached. Conclusions: The CDK4-selective inhibitor BGB-43395, in combination with letrozole, demonstrated a favorable safety profile, with low hematologic and manageable gastrointestinal toxicity. Antitumor activity in 1L tx of pts with advanced HR+/HER2− BC was promising. Doses of 400 mg and 240 mg BID demonstrated efficacy and safety that support further development in combination with letrozole. Clinical trial information: NCT06120283 . BGB-43395 BID dose + letrozole 240 mg (n=19) 400 mg (n=19) 600 mg (n=20) Median tx follow-up, mo 7.0 7.1 5.2 Best overall response, % PR a 58 68 40 SD 37 32 55 PD 5 0 0 NE 0 0 5 Objective response rate (CR + PR), %(95% CI) 58(33-80) 68(43-87) 40(19-64) Disease control rate (CR + PR + SD), %(95% CI) 95(74-100) 100(82-100) 95(75-100) RECIST v1.1 (investigator). a Unconfirmed.
A multicenter randomized controlled clinical study of neoadjuvant combination of axitinib plus toripalimab to improve disease-free survival of patients with renal cell carcinoma.
TPS4630 Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma, accounting for 75-80% of cases worldwide and 60-85% in China. High risk ccRCC includes tumors larger than 7 cm (T2 stage) or those at advanced stages (≥T3 or N1). Surgical resection is standard, but 30% may have recurrence, with a 2-year disease-free survival rate of 68%. Neoadjuvant therapy with axitinib and toripalimab may enhance antitumor immunity and improve prognosis for high risk patients. Methods: This is an open-label, multicenter, phase III randomized controlled study to assess whether neoadjuvant axitinib plus toripalimab improves disease-free survival (DFS) compared with surgery alone in patients with ccRCC at high risk of recurrence. The study is designed to enroll 298 patients with high risk ccRCC (T2G4 or T3-4 or N1) scheduled for nephrectomy. Patients must provide an adequate tumor tissue sample at screening for molecular and immune profiling. Patients will be randomly assigned to the control group or the neoadjuvant group at a 1:1 ratio. Both groups will undergo nephrectomy, while the neoadjuvant group will additionally receive preoperative treatment with axitinib plus toripalimab. Axitinib will be given for 3 months, 5 mg twice daily, orally. Toripalimab will be administered at 240 mg intravenously every 3 weeks for 4 cycles (one cycle every 3 weeks). Blood samples are collected before and after neoadjuvant treatment for exploratory molecular analysis. CT or MRI assessments will be conducted after 2 cycles of medication and before surgery. Radical nephrectomy (or partial nephrectomy, if applicable) will be performed within 1-28 days after completion of neoadjuvant therapy. For both groups, if postoperative pathology meets high recurrence risk criteria per Keynote-564—specifically, T2G4, T2 with sarcomatoid differentiation, T3, T4, any T stage with lymph node metastasis, or M1 with no evidence of disease—1 year of adjuvant toripalimab is recommended according to NCCN and EAU guidelines. Eligible patients must be diagnosed as ccRCC or RCC with a predominant clear cell component through histopathological examination. Clinical staging via CT or MRI must indicate T2, while biopsy pathology should show either nuclear grade 4 or sarcomatoid differentiation, or a classification of T3-4 or N1. Additional inclusion criteria include: signed informed consent, age ≥18 and < 80 years old, adequate organ function, ECOG of 0 or 1 point. The primary endpoint is 2-year DFS, defined as the time from randomization to disease recurrence or death from any cause. Secondary endpoints include cancer-specific survival, overall survival, objective response rate, major pathological response, and safety profile. Enrollment began in April 2023, and 112 of the planned 298 patients have been enrolled. Clinical trial information: NCT05738694 .
Clinical characteristics and prognostic analysis of epidermal growth factor receptor–mutated non–small cell lung cancer patients with malignant pleural effusion.
e20755 Background: Malignant pleural effusion (MPE) is common in advanced non-small cell lung cancer (NSCLC) and typically indicates poor prognosis. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line treatment for EGFR-mutated NSCLC, significantly improving survival and quality of life. This study explores the heterogeneous impact of MPE on survival outcomes in NSCLC patients receiving EGFR-TKIs across different clinical scenarios. Methods: This single-center retrospective study enrolled histologically or cytologically confirmed NSCLC patients. The MPE group underwent Indwelling Pleural Catheter (IPC) drainage with cytological confirmation. All patients had confirmed EGFR mutations and received first-line EGFR-TKI therapy. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included Objective Response Rate (ORR) and Disease Control Rate (DCR). Results: From March 2017 to September 2024, 162 patients were enrolled: 48 with MPE at diagnosis and 114 without. After 1:2 Propensity Score Matching (PSM), 91 patients were analyzed, including 35 with MPE. Compared to those without MPE, patients with MPE had significantly shorter median PFS (10.0 vs. 14.2 months; HR 1.872, 95% CI 1.196–2.928; p = 0.005) and median OS (28.3 vs. 33.8 months; HR 1.877, 95% CI 1.130–3.118; p = 0.013). Among 71 patients receiving first-line third-generation EGFR-TKIs after PSM (28 with MPE), those with MPE also showed significantly shorter mPFS (10.6 vs. 16.6 months; HR 2.116, 95% CI 1.265–3.539; p = 0.003) and mOS (28.3 vs. 38.5 months; HR 2.183, 95% CI 1.155–4.128; p = 0.014). Subgroup analyses suggested that the prognostic effect of MPE varied across different clinical subgroups (e.g., brain, liver, bone metastases), indicating that its impact may be modulated by metastatic patterns and other clinical characteristics. Conclusions: In the context of standard first-line EGFR-TKI therapy, patients with MPE had significantly reduced survival benefits. Even with first-line third-generation EGFR-TKIs, their survival remained markedly inferior to those without MPE. In the current EGFR-TKI treatment landscape, risk stratification based solely on MPE presence may be inadequate. Incorporating clinical subgroup characteristics into a refined assessment could enable more accurate prognostic evaluation.
Disparities in mycosis fungoides outcomes: A multivariate survival and prevalence study.
e19117 Background: Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma. It is characterized by the infiltration of malignant T-cell clones into the skin. The diagnosis can be challenging and requires careful clinicopathological correlation. The purpose of this study is to determine sociodemographic disparities and survival trends in patients with MF. Methods: Total 10450 cases of MF were collected from SEER Plus Database, 17 Registries, Nov 2024 Sub (2000-2022), using the ICD Code 9700/3. A multivariate Cox regression model was used to examine the effects of independent variables including age [continuous variable], sex [reference=males], race [ref=Caucasians], year of diagnosis [continuous variable], stage [ref=locoregional], median household income inflation adjusted to 2023 [ref= <100K], and treatment including surgery, chemotherapy (CTX), XRT [ref=no Tx utilized, respectively] on the survival. Dependent variables were survival (months) and an event (1=death, 0=censored). All analysis was conducted using GraphPad Prism 10.6.1. Results: Of the dataset, 57.6% were males. Racial distribution was: 60.6% Caucasians and 39.4% non-Caucasians races. Median age was 66 years. The overall median of survival was 255 months, with a 1-year OS of 95.99% (CI 95%, 95.6%-96.4%) and 5-year OS of 82.95% (CI 95%, 82.14%-83.7%). The overall Cox proportional hazards model for multivariate analysis was statistically significant (p < 0.05). The results of the model are shown in Table 1. Conclusions: Our analysis showed that for every 1-year increase in age, the hazard of death increased by 7.7%. While the risk of death reduced by 2.2% for every following year from 2000 to 2022 as the year of diagnosis. Females had 23% less risk of death compared to males. However, non-Caucasian origin was associated with 1.25-fold increased risk and distant stage with 2.84-fold increased risk of death compared to Caucasian origin and locoregional disease, respectively. Income above 100K showed 0.74-fold risk compared to those making less than 100K. Chemotherapy showed 1.82-fold higher hazard risk and XRT showed 1.74-fold higher risk of death compared to no CTX and no XRT, respectively. Higher risk with CTX and XRT are likely attributed to their use in advanced disease states rendering higher HR in those cohorts of patients. No significant association was found between surgical management with survival. Higher HR with treatment warrants exploration of targeted chemoimmunotherapy based on next generation sequencing to mitigate the overall risk. Variables HR 95% CI P value Age 1.077 1.074 – 1.081 <0.0001* Gender [female] 0.771 0.713 – 0.833 <0.0001* Race [non-Caucasians] 1.252 1.151 – 1.36 <0.0001* YOD 0.978 0.9707 – 0.9852 <0.0001* Stage [distant] 2.843 2.25 – 3.54 <0.0001* Surgery [yes] 1.018 0.927 – 1.116 0.7065 Chemotherapy [yes] 1.816 1.67 – 1.975 <0.0001* XRT [yes] 1.735 1.56 – 1.924 <0.0001* Income [>100K] 0.743 0.68 – 0.81 <0.0001*
Fusion-positive early-stage and locally advanced lung cancers: A real-world analysis of event-free, disease-free, and overall survival.
8036 Background: Fusion-positive lung cancers are a distinct subset of lung cancers. While outcomes in metastatic disease are comprehensively characterized, data on survival and disease recurrence outcomes after definitive therapy in non-metastatic disease remain limited. Methods: This was a single institution, retrospective study, including patients (pts) with ALK/ROS1/RET/NTRK+ early-stage/locally advanced lung cancer pts diagnosed between 2012-2025. The primary endpoint in pts who underwent curative surgery or stereotactic body radiotherapy (SBRT) was disease-free survival (DFS; time from curative therapy to disease recurrence or death). The primary endpoint in pts initially treated with neoadjuvant therapy prior to surgery or definitive chemoradiation was event-free survival (EFS; time from curative therapy to disease progression, recurrence, failure of treatment or death). Overall survival (OS) from the start of curative therapy was analyzed. Results: 179 pts (82 ALK , 38 ROS1 , 55 RET , 4 NTRK ) were identified. Median EFS across all pts for ALK/ROS1/RET/NTRK was 4.4yrs (95%CI: 2.8, Not Reached (NR)), 3.4yrs (95%CI: 2.0, NR), 7.4yrs (95%CI: 4.6, NR) and 3.0yrs (95%CI: 0.4, NR), respectively. Median OS for ALK/ROS1/RET/NTRK pts was: 13.0yrs (95%CI: 12.0, NR), 12.0yrs (95%CI: 11.0, NR), 14.0yrs (95%CI: 12.0, NR) and NR (95%CI: 5.4, NR), respectively. 132/179 (74%) of all pts were treated with surgery (128 pts) or SBRT (4 pts) first. Median EFS for pts treated with neoadjuvant treatment first (N=26) for ALK (n=15) /ROS1 (n=5) /RET (n=6) pts was 0.9yrs (95%CI: 0.8, NR), 0.9yrs (95%CI: 0.7, NR) and NR (95%CI: 0.2, NR), respectively. Median EFS for pts treated with chemoradiation first (N=21) for ALK (n=7) /ROS1 (n=5) /RET (n=9) pts was NR (95%CI: 0.5, NR), 0.6yrs (95%CI: 0.5, NR) and 1.0yrs (95%CI: 0.8, NR), respectively. Median DFS for pts treated with surgery/SBRT first (N=132) for ALK (n=60) /ROS1 (n=28) /RET (n=40) /NTRK (n=4) pts was: 5.1yrs (95%CI: 3.8, NR), 5.2yrs (95%CI: 3.2, NR), NR (95%CI: 6.6, NR) and 3.0yrs (95%CI: 0.4, NR), respectively. Conclusions: This is the largest series on outcomes in fusion-positive early stage/locally advanced lung cancers treated with definitive therapy. Prolonged EFS, DFS, and OS were observed.
Role of palliative care nurse coordination in symptom control and care planning.
12063 Background: Effective coordination by palliative care nurses plays a central role in improving communication, symptom assessment, and timely care planning for patients with advanced cancer. However, evidence on the measurable impact of nurse-led palliative coordination—particularly in Asian oncology settings-remains limited. This study evaluates the outcomes of a nurse-coordinated palliative care model on symptom control and care planning among patients with advanced cancer. Methods: This retrospective observational study included patients with advanced cancer who received palliative care nurse coordination from January 1, 2025 to December 31, 2025. The intervention consisted of systematic ESAS-based symptom assessment, coordination with oncology teams, family meetings, and facilitation of advance care planning. Outcomes included changes in symptom scores from baseline to follow-up, completion of advance care planning (ACP) and DNR documentation, and health-care utilization indicators.Distress score was derived from the ESAS psychological subscale, calculated as the sum of anxiety and depression scores. Descriptive statistics and paired comparisons were used for analysis. Results: A total of 195 patients were included (mean age 60.5 years; range 21–100). Following nurse-led palliative coordination, median pain scores decreased from 8 to 3 (p < 0.01). Median dyspnea scores improved from 6 to 1, representing an 83.3% reduction (p < 0.01). Median distress scores decreased from 6 to 2, corresponding to a 66.7% improvement (p < 0.01).Completion of advance care planning increased from 10% to 97%. DNR documentation improved from 20% to 80%, with the exception of one Arabic patient for whom DNR documentation was not completed. Under the nurse-led palliative care coordination model, 98.5% of patients with advanced cancer did not require unplanned emergency room utilization and avoided unnecessary ICU admissions. These outcomes highlight the effectiveness of proactive symptom management and comprehensive care planning. Conclusions: Nurse-led palliative care coordination was associated with significant improvements in symptom control and substantially higher completion rates of care planning among patients with advanced cancer. These results support integrating palliative nurses as key coordinators in oncology settings to enhance patient-centered and goal-concordant care.
Pregnancy and cancer: A retrospective case series of obstetric, oncologic, and care-compliance outcomes.
e13549 Background: Two million women of reproductive age are diagnosed with cancer annually. Advances in cancer therapies have led to more women achieving pregnancy during or shortly after cancer diagnosis. These patients represent a clinically vulnerable population more likely to experience obstetrical and neonatal complications. We describe obstetric, oncologic, and care-compliance outcomes in patients with pregnancy-associated cancer and pregnancy occurring shortly after malignancy in a tertiary care medical center. Methods: We conducted a retrospective descriptive case series. Patients ≥ 18 years old with cancer who became pregnant January 2020-January 2025 were identified through ICD-10 codes. Patients were included if diagnosed with cancer during pregnancy or if pregnancy occurred within five years of cancer diagnosis without documented long-term remission. Those in remission beyond five years were excluded. Electronic medical records were reviewed for demographics, gynecologic history, malignancy history, and pregnancy outcomes. Compliance, defined as attending two and six-week postpartum obstetric visits and oncology appointments up to six months postpartum, was recorded. Descriptive statistics were used. Results: The cohort (n = 20) was majority black non-Hispanic (45%) with public insurance (50%). Average age at cancer diagnosis was 30.8 years (SD = 7.5) and 33.6 years (SD = 5.1) at pregnancy. Breast cancer (25%) was the most represented cancer type followed by sarcoma (15%), lymphoma (15%), cervical cancer (15%). Remaining cases included melanoma, astrocytoma, ovarian cancer, leukemia, and cholangiocarcinoma (each 5%). Pregnancy outcomes included spontaneous vaginal delivery (40%), cesarean delivery (30%), spontaneous abortion (15%), and termination (15%). Among live births, 57% were preterm ( < 37 weeks). Maternal complications included pre-eclampsia (36%) and preterm premature rupture of membranes (14%). Non-attendance occurred in 46% of patients for obstetric follow-up and 30% for oncology follow-up. Four patients (20%) experienced cancer progression during pregnancy or within six months postpartum. These patients were more likely to have ongoing disease activity one year after diagnosis. No clear associations were observed between visit compliance and short-term survival outcomes. Conclusions: This study highlights the complexity of pregnancy in patients with active or recent malignancy in a predominantly minority population. High rates of obstetric complications and preterm birth were observed. Compliance with peripartum obstetric and oncologic care was suboptimal, reflecting the vulnerability of this population. Limitations include small sample size and incomplete external records. Larger, multi-center studies are needed to better define maternal, neonatal, and oncologic outcomes and to develop interventions to improve care.
Benefits of utilizing experiential learning in a medical school cancer survivorship course.
9018 Background: Cancer survivorship care remains underemphasized in medical education despite a growing population of cancer survivors with complex long-term needs. Identifying effective strategies to integrate survivorship education into the medical curriculum is essential. Kolb’s experiential learning theory, which posits that effective learning occurs through iterative cycles of concrete experience, reflective observation, abstract conceptualization, and active experimentation, may offer a structured framework well suited to teaching survivorship care. Methods: We evaluated the effectiveness of utilizing repeated Kolb’s cycles to teach a 15-week cancer survivorship course during our 2024 Fall semester. 12 learners (9 pre-clerkship medical students and 3 premedical students) attended weekly sessions mediated by the instructor and invited guests. In-class experiences were paired with reflective homework assignments also tasking students to develop new concepts in 4 domains of interest: patients as survivors (PS), caregivers’ issues (CI), illness experience (IE), and interprofessional care (IPC). Students shared concepts in the next session then began the Kolb's cycle again. For their final assignment, they interviewed a cancer survivor then created a treatment plan applying the concepts they developed during the course. An anonymous post-course survey assessed learner satisfaction and perceptions of Kolb’s cycle, and a one-year follow-up survey evaluated comfort addressing survivorship issues during clerkships and the course’s impact on survivor care. Results: Students generated 259 new concepts (PS: 74; CI: 49; IE: 56; and IPC: 80) across the course and applied an average of ten self-developed concepts per student on the final assignment. On the immediate post-course survey, 12/12 students were highly satisfied with the course and 9/12 students rated all four stages of Kolb’s cycle as extremely or mostly helpful. A year later, 6/9 medical students now on clinical clerkships responded to a follow-up survey. Most reported that the course had a significant lasting impact on their understanding of survivorship issues (4/6) and overall patient management (4/6). Qualitative comments describe greater holistic awareness, comfort with difficult conversations, and attention to survivorship-focused referrals. Students also reported being extremely or mostly confident addressing survivorship issues in the following domains: PS 4/6, CI 3/6, IE 4/6, and IPC 3/6. Conclusions: Kolb’s experiential learning theory is an effective framework for teaching a cancer survivorship course to pre-clerkship medical students. Students were highly satisfied with this learning method and able to use this model to successfully develop and apply new concepts. Follow-up during clerkships demonstrated sustained learning and a lasting capacity to apply this material to new patient encounters.
Fruquintinib in combination with camrelizumab, paclitaxel liposome, and nedaplatin as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): Updated results from a single-arm, phase II study.
e16070 Background: Our preliminary results suggested potential synergistic activity of fruquintinib combined with camrelizumab, paclitaxel liposome, and nedaplatin in first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). Here we present updated findings from our study (NCT06010212). Methods: This study included a dose-finding (3+3 design) phase to determine the recommended phase 2 dose (RP2D) of fruquintinib and a dose-expansion phase in which patients received camrelizumab (200 mg), paclitaxel liposome (135 mg/m²), and nedaplatin (70 mg/m²) on day 1 of each 3-week cycle, along with fruquintinib 5 mg daily on days 1-14 of each cycle. A maximum of six cycles was administered, followed by maintenance therapy with fruquintinib and camrelizumab. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and safety. Results: AS of December 15, 2025, 34 patients (median age 66; 29 males) were enrolled. Patients with three or more organ metastases accounted for 41.2% (14/34), primarily involving lymph nodes (91.2%, 31/34), lung (47.1%, 16/34), and liver (32.4%, 11/34). Tumors were G3 in 29.4% (10/34) of patients. Radical surgery was performed in 23.5% (8/34) of patients, and adjuvant chemotherapy was administered in 11.8% (4/34) of patients. Among intention-to-treat population (34 patients), the confirmed ORR was 64.7% (22/34; 95% CI: 48.6%–80.8%) and DCR was 94.1% (32/34; 95% CI: 80.3%–99.3%). At a median follow-up of 16.1 months and 15.3 months, the median PFS was 13.7 months (95% CI: 10.3–not reached [NR]) and the median OS was NR (95% CI: 18.8–NR). The 1-year PFS rate and 1-year OS rate were 58.6% and 83.9%, respectively. Treatment-related adverse events (TRAEs) occurred in 33 patients (97.1%). The most common(≥40%) TRAEs were anemia (82.4%), hypoproteinemia (50.0%), and nausea (41.2%). Grade ≥3 TRAEs were observed in 13 patients (38.2%), most commonly (≥10%) neutropenia and leukopenia (20.6% each). Dose modifications (discontinuation or dose reduction) due to TRAEs were necessary in 15 of 34 patients (44.1%). No serious adverse events occurred. Conclusions: The combination of fruquintinib, camrelizumab, paclitaxel liposome, and nedaplatin demonstrated encouraging anti-tumor activity with a manageable toxicity profile as a first-line treatment for advanced ESCC, warranting further investigation in larger, randomized studies. Clinical trial information: NCT06010212 .
Depletion of T-regulatory cells by denileukin diftitox-cxdl (E7777) in combination with pembrolizumab in relapsed/refractory (r/r) gynecologic malignancies: Phase 1 study results.
2564 Background: Denileukin diftitox-cxdl (E7777) is an FDA-approved direct cytotoxic agent that depletes T-regulatory cells by targeting the IL-2 receptor. Pre-clinical studies have demonstrated synergistic activity between the immunomodulator E7777 and PD-1 immune checkpoint inhibitor (ICI). Here, we report positive results from a phase I study of E7777 + pembrolizumab (P) in r/r gynecological (GYN) malignancies. Methods: Phase I dose-escalation trial of E7777 given at 4 IV dose levels (DL): 3, 6, 9, and 12 mg/kg on days 1-3, combined with P (IV 200 mg, day 1) in a 21-day cycle x8, followed by maintenance P until progression. Dose-limiting toxicities (DLTs) were assessed during cycle 1 according to CTCAE v5 criteria. Responses were measured using the RECIST 1.1 criteria. Blood samples were collected for translational studies. Results: Pt demographics included: median age 64y (43, 88); race, 88% white; histology 40% endometrial, 36% ovarian. Of the 24/25 pts evaluable for DLTs, only 1 case of reversible capillary leak syndrome (CLS) was seen at DL4. Anemia, fatigue, chills, and hypoalbuminemia were the most common AEs. A comprehensive overview of AEs, SAEs, and immune-related adverse events (irAEs) will be presented at the annual meeting. Table 1 describes the 4 DLs and their responses in the 21 pts evaluable for efficacy. An ORR of 24% (5 PRs) was reported in this heavily pretreated patient population with a mDOR of 21.1m (4.2-35.0). E7777 + P responses were seen in patients who progressed on prior ICI therapy, and across different GYN histologies. The median Progression-free survival (mPFS) was 5.8 m (1.1 – 37), with 5 pts having a PFS of ≥20 months. The clinical benefit rate (CR; PR; SD ≥ 6 m) was demonstrated in 48% of pts (n=10), who achieved a mPFS = 17.4m (6.2 – 37); patients with documented PD had a mPFS = 2.1 m (1.1 – 4.7). Conclusions: The results from this Phase I study of two immunomodulatory agents in combination, E7777 + P, in patients with r/r GYN tumors was well tolerated and demonstrated promising efficacy. A max tolerated dose wasn't established. No new significant safety signals or irAEs were reported. ORR of 24 % was demonstrated. Responders achieved a mDOR of 21.1m (4.2 - 35.0) and a mPFS = 23 m (10.4 – 37.0). Thus, E7777 + P showed prolonged responses and clinical benefit in pts with r/r GYN malignancies and limited options. These results will inform a Phase II study. Clinical trial information: NCT05200559 . Response- evaluable patients (RECIST v1.1) DL1 (N=3) DL2 (N=2) DL3 (N=6) DL4 (N=10) Total (N=21) Best response CR 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) PR 1 (33.3%) 0 (0%) 1 (16.7%) 3 (30.0%) 5 (23.8%) SD 1 (33.3%) 1 (50.0%) 2 (33.3%) 2 (20.0%) 6 (28.6%) PD 1 (33.3%) 1 (50.0%) 3 (50.0%) 5 (50.0%) 10 (47.6%) CBR w/ Durable SD (CR/PR/SD≥ 6m) 2 (66.7%) 1 (50.0%) 2 (33.3%) 5 (50.0%) 10 (47.6%) PD 1 (33.3%) 1 (50.0%) 4 (66.7%) 5 (50.0%) 11 (52.4%)
Integrating personalized ctDNA into clinical surveillance of soft tissue sarcoma: Performance, timing, and histologic insights.
11581 Background: Soft tissue sarcoma (STS), particularly larger and biologically aggressive subtypes, carries a high risk of relapse making effective post-operative surveillance essential. CtDNA utility in STS remains elusive. Methods: We conducted a retrospective review of STS who underwent surgical resection and post-operative surveillance with serial personalized ctDNA testing (Signatera) and cross-sectional imaging between April 2023- January 2026. Diagnostic performance was assessed by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), using imaging-confirmed progression as the reference standard. Subgroup analyses by major histologic subtype conducted. Detection times were referenced to surgery, and lead time was summarized using medians and interquartile ranges (IQR). Paired detection times were compared using the Wilcoxon signed-rank test, with Mann–Whitney U test as a sensitivity analysis. Results: Total 114 patients with ctDNA samples were screened. 101 patients with paired ctDNA ( total 1,005 plasma samples) and imaging surveillance were included. The median age at diagnosis was 53 years, and the cohort was evenly distributed by sex (50.5% male, 49.5% female). Most patients were White (86.1%), 13.9% African American; 58.4% identified as non-Hispanic and 40.6% as Hispanic. Using imaging as the reference standard, 33 patients developed radiographic progression. ctDNA was positive in 27, yielding a sensitivity of 81.8% (95% CI, 65.6%–91.4%). Among 68 patients without progression, 66 remained ctDNA negative, corresponding to a specificity of 97.1% (95% CI, 89.9%–99.2%). The PPV and NPV were 93.1% and 91.7%, respectively. Six patients (18.2%) had radiographic progression despite persistently negative ctDNA, forming a clinically relevant discordant subgroup. Among patients with paired molecular and radiographic progression (n = 27), ctDNA detected progression earlier in 44%, while imaging led in 56%. Overall detection timing did not differ significantly between modalities (median lead time, –0.21 months; IQR, –1.42 to 1.67; p = 0.91). Tumors associated with ctDNA positivity were numerically larger than ctDNA-negative (median, 8.75 cm vs 7.0 cm, p = 0.051). CtDNA detection dynamics varied by histologic subtype, with a nonsignificant numerical trend toward earlier detection in synovial sarcoma. The most common site of metastatic involvement was lung (40%), followed by liver (20%). Conclusions: Personalized ctDNA surveillance showed high specificity and strong diagnostic performance in STS and detected progression earlier than imaging in a subset of patients, though no overall lead-time advantage was observed. Histology-specific differences suggest biologic variability in ctDNA detectability and support prospective, subtype-focused studies to define optimal integration with imaging.
Impact of mRNA COVID-19 vaccination on survival in pembrolizumab-treated stage IV colon cancer: A multi-institutional propensity-matched analysis.
e15624 Background: Colon cancer remains a leading cause of cancer-related mortality. While immune checkpoint inhibitors (ICIs) like pembrolizumab have revolutionized treatment for advanced microsatellite instability-high (MSI-H/dMMR) colon cancer, methods to further improve survival is needed. Recent data have confirmed the safety of mRNA COVID vaccines in patients on ICIs, with emerging studies in melanoma and NSCLC even suggesting a potential synergistic effect whereby peritherapeutic mRNA COVID vaccines may enhance ICI efficacy and lead to improved survival. However, the clinical impact of this association in colon cancer remains unexplored. This study sought to evaluate whether mRNA COVID vaccination improves survival in patients with stage IV colon cancer receiving pembrolizumab. Methods: A retrospective cohort study was conducted using the TriNetX database. We identified stage IV colon cancer patients treated with pembrolizumab between 12/11/2020 and 01/26/2023. Group 1 (Vaccine) received an mRNA COVID vaccine within ±12 months of their first pembrolizumab infusion; Group 2 (Control) did not. Patients with skin or respiratory malignancies synchronous with colon malignancy were excluded to account for pembrolizumab treatment not targeting colon cancer. Propensity score matching (1:1) was performed based on age, sex, race, and comorbidities (diabetes, hypertension, obesity, heart disease, tobacco use, and liver disease). Primary outcome was median overall survival at 3 years (end date: 01/26/2026). Results: Following 1:1 propensity score matching, 374 patients were included in the final analysis (Vaccine group, n = 188; Control group, n = 186). Kaplan-Meier analysis revealed no statistically significant difference in survival between patients the vaccine group and the control group. Median survival for the vaccine cohort was 879 days, while median survival for the control cohort was not reached. At the end of the 3-year period, survival probability was 43.3% in the vaccine group and 50.4% in the monotherapy group, with a log-rank p-value of 0.308, suggesting that COVID-19 vaccination did not significantly impact survival outcomes in this cohort. Cox proportional analysis revealed no statistically significant difference in survival (HR 1.163; 95% CI 0.870-1.553). Conclusions: In this retrospective cohort study, mRNA COVID vaccination within a year of the first pembrolizumab infusion did not affect survival in stage IV colon cancer. This suggests that previous positive findings regarding vaccination during pembrolizumab therapy in other cancers might not extend to colon cancer. Limitations of our study include our assumption that all stage IV colon cancer patients treated with pembrolizumab were MSI-H due to inherent limitations preventing stratification by MSI-H status on the TriNetX platform.
Clinical outcomes and safety of trifluridine–tipiracil with or without bevacizumab in metastatic colorectal cancer: A real-world study from Saudi Arabia.
e23415 Background: Trifluridine–tipiracil (TAS-102) is an established later-line therapy for metastatic colorectal cancer (mCRC). However, real-world data describing clinical outcomes and prognostic factors—particularly from Middle Eastern populations—remain limited. Our aim was to assess the safety and efficacy of TAS-102 with or without bevacizumab in patients with mCRC at a single center in Saudi Arabia. Methods: We conducted a retrospective cohort study of adults with mCRC treated with TAS-102, with or without bevacizumab, at King Fahad Medical City (KFMC), a tertiary care center in Saudi Arabia, between 2020 and 2025. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), safety, and identification of prognostic factors. Survival outcomes were estimated using the Kaplan–Meier method, and associations were evaluated using Cox proportional hazards regression. Results: A total of 111 patients were included (mean age 60.1 ± 11.8 years; 53.2% female). TAS-102 was administered as third-line therapy in 84.7% of patients, and 62.2% received concomitant bevacizumab. At a median follow-up of 8.8 months, median PFS was 2.9 months (95% CI, 2.3–3.5) and median OS was 12.3 months (95% CI, 10.9–14.8). Compared with TAS-102 alone, the addition of bevacizumab was associated with improved PFS (3.4 vs 2.1 months; p = 0.005) and OS (14.8 vs 9.0 months; p = 0.006). On multivariable analysis, liver metastases were independently associated with poorer OS (HR 2.50; 95% CI, 1.37–4.55; p = 0.003), while KRAS mutation was associated with shorter PFS (HR 1.76; 95% CI, 1.16–2.69; p = 0.008). Grade ≥3 neutropenia and anemia occurred in 18.0% and 9.9% of patients, respectively. Conclusions: In a real-world cohort of heavily pretreated patients with mCRC, TAS-102 demonstrated clinical outcomes comparable to those reported in clinical trials. The addition of bevacizumab was associated with improved survival without unexpected safety signals. KRAS mutation status and the presence of liver metastases were associated with prognosis and may support risk stratification and treatment decision-making in routine clinical practice.