tbuckley/cabot-search huggingface dataset:
Disparities and barriers in germline testing among patients with early-onset gastrointestinal cancers.
Authors: Gideon T Dosunmu, Susan Feldt, Manish Pathuri, Guimin Gao, Namrata Setia, Ardaman Shergill
Journal: Journal of Clinical Oncology (2025)

35 Background: Early-onset gastrointestinal cancers (EOGIC) are strongly associated with hereditary predisposition, making germline testing essential for treatment and familial risk management. Disparities in germline testing persist. This study investigates disparities and barriers to germline testing in EOGIC. Methods: This IRB-approved retrospective analysis included 864 patients aged 18-49 with GI cancers at the University of Chicago (2018-2023). Data collected included race, gender, age, insurance, family cancer history, and subtype. Outcomes were physician referrals for germline testing and completion. Chi-square tests and logistic regression models assessed predictors of recommendations and completion. Results: Of 864 patients, 473 (54.7%) received germline testing recommendations, and 323 (37.4%) completed testing. Completion rates: 30.2% for no insurance, 29.1% for Medicare/Medicaid, and 40.3% for private insurance (p=0.032). Patients with family history of cancer were more likely to be recommended for testing (62.9% vs. 39.5%, p&lt;0.001) and complete it (44.0% vs. 23.7%, p&lt;0.001). In our cohort, no significant racial disparities were observed (p=0.712 and p=0.358). Females were more likely to receive recommendations (59.1%) and complete testing (41.2%) than males (50.9% referral, 34.0% completion, p=0.016 and p=0.029). Patients under 30 had the highest rates of testing recommendation (66.1%) and completion (46.4%), followed by 30-39 (61.7%, 44.4%) and 40-49 (51.2%, 34.0%), p=0.006 and p=0.009. By cancer subtype, colorectal cancer (CRC) patients had the highest referral (66.1%) and completion (45.9%) rates, while anal cancer had the lowest (13.2% referral, 5.3% completion, OR 0.08, p&lt;0.0001). Gastric cancer (52.3% referral, 29.2% completion, OR 0.49, p=0.005) and esophageal cancer (36.9% referral, 20.0% completion, OR 0.31, p&lt;0.0001) also had lower testing rates. Liver cancer (35.4% referral, 27.1% completion, OR 0.38, p&lt;0.0001) and cholangiocarcinoma (45.5% referral, 22.7% completion, OR 0.28, p=0.016) showed similarly low rates. Conclusions: Disparities in germline testing were seen among uninsured patients, males, and those with public insurance. CRC had the highest testing rates, while anal, esophageal, liver, and cholangiocarcinoma had lower rates, likely due to lower suspicion of hereditary predisposition. Targeted interventions are needed to improve testing uptake and completion, especially among uninsured and underrepresented populations.
Chemoradiotherapy (CRT) followed by sequential tislelizumab (TIS) + CAPOX and TIS monotherapy for organ preservation in locally advanced low rectal cancer.
Authors: Wentao Tang, Ye Wei, Guiying Wang, Rui Zhang, Haiyang Zhou, Zizhen Zhang, Jianmin Xu
Journal: Journal of Clinical Oncology (2025)

TPS315 Background: CRT followed by total mesorectal excision (TME) is the standard care for patients with locally advanced low rectal cancer (≤ 5cm from the anal margin). However, TME may lead to permanent colostomy and severely impact quality of life. Organ preservation is, therefore, a critical unmet need for these patients. The proportion of patients achieving clinical complete response (cCR) after CRT is relatively low, with the literature reporting around 20%. Total neoadjuvant therapy (TNT) has been investigated to increase cCR rate. Several clinical trials demonstrated that PD-1 inhibitor combined with TNT could result in significate improvement in pathological complete response rate (pCR rate, 39.8% vs 15.3%, p &lt; 0.001 in UNION study) or complete response rate (pCR+cCR rate, 44.8% vs 26.9%, p = 0.031 in a randomized phase 2 study) compared with TNT alone in rectal cancer patients. The RELIEVE-01 study (NCT06390982) was designed to evaluate the efficacy in organ preservation with CRT followed by sequential TIS + CAPOX and TIS monotherapy in patients with low rectal cancer. Methods: This multicenter, single-arm, phase 2 study will enroll 46 pts with histopathologically confirmed rectal adenocarcinoma (≤ 5cm from the anal margin), pMMR/MSI-L/MSS, cT1-3N1M0/T2-3N0M0, and ECOG PS ≤1. Pts will initially receive 6 weeks of CRT (50.4 Gy/28F, capecitabine 825 mg/m 2 , bid, d1-5 each week), followed by 4 cycles of TIS + CAPOX (TIS, 200 mg, IV, d1; capecitabine 1000 mg/m 2 , bid, d1-14; oxaliplatin 130 mg/m 2 , d1) in a 21-day cycle. Then, clinical response will be assessed to determine the subsequent treatment. Patients with cCR will receive TIS + CAPOX (4 cycles) and TIS (up to 9 cycles), and then be managed using the W&amp;W strategy. Patients with non-cCR will undergo TME. Patients with near-cCR will be given local excision, and those achieving pCR will receive the same treatment as cCR patients, and for those with non-pCR after local excision, TME will be performed. The primary endpoint is rate of CR (cCR plus pCR post local resection). Secondary endpoints include organ-preserving rate, event-free survival rate and OS rate at 1, 2 and 3 years, respectively. Recruitment is ongoing. Clinical trial information: NCT06390982 .
Retreatment with immune checkpoint inhibitors (ICIs) for patients with advanced gastric cancer: A retrospective, real-world study.
Authors: Yong-Xu Jia, Yihan Liu, Hui-Qiong Han, Ya-Ping Gao, Yanru Qin
Journal: Journal of Clinical Oncology (2025)

343 Background: Immunotherapy combined with chemotherapy has become the standard first-line treatment for advanced gastric cancer and is recommended by multiple guidelines and consensuses. After the first line immunotherapy, there is still controversy over whether immune inhibitors can continue to be used across lines after progression. Methods: This is a single-center, retrospective, observational, real-world study. We collected clinical information of patients with advanced gastric cancer hospitalized at the First Affiliated Hospital of Zhengzhou University from January 2018 to July 2024. All patients received combination therapy with ICIs inhibitors for at least 2 cycles in the first-line and at least 2 cycles of ICI inhibitor-based therapy in the second-line after first-line progression. The efficacy and safety of treatment were evaluated, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), the progression pattern of retreatment with immune checkpoint inhibitor, grade 3-5 treatment-related adverse events (TRAEs), and immune-related adverse events (irAEs). Cox regression model was used to investigate the influence of multiple factors on survival. Results: We included 217 patients with a median age of 59.0 (18-84) years, of which 70.0% were male. The median OS and PFS were 9.8 (95% CI 8.8-10.8) months and 4.6 (95% CI 4.0-5.3) months. The ORR and DCR were 22.7% (95% CI 17.1-29.0) and 56.2% (95% CI 49.0-63.1). For the second-line treatment regimens, there were 87 (40.1%) patients and 130 (59.9%) patients received immunotherapy combined with chemotherapy (I+C) and immunotherapy combined with chemotherapy and anti-angiogenic drugs(I+C+A) respectively. The median OS was 9.3 (95% CI 8.5-10.1) months and 11.5 (95% CI 9.3-13.7) months, p=0.032. The median PFS was 4.2 (95% CI 3.1-5.3) months and 5.2 (95% CI 4.3-6.1) months, p=0.082. Cox regression model analysis showed that ECOG 0-1, PFS≥6 months in the first-line treatment, second-line regimen (I+C+A), and second-line medication &gt; 3 cycles were independent prognostic factors for OS in the second-line treatment. The incidence of grade ≥3 TRAEs was 20.7%, and the incidence of irAEs was 6.5%. No treatment-related deaths occurred. Conclusions: This real-world study results showed that retreatment with immune checkpoint inhibitors had promising clinical benefit for patients with advanced gastric cancer and manageable safety. Efficacy of different groups. n mOS（m） mPFS（m） ORR（%） DCR（%） ITT 217 9.8 4.6 22.7 56.2 ECOG 0-1 180 9.8 4.7 19.5 56.8 2 37 8.6 4.0 38.2 52.9 1-Line PFS ＜3m 61 5.5 2.2 1.7 17.2 ≥3m 156 11.7 6.0 31.0 71.7 ＜6m 136 7.4 3.2 2.4 38.7 ≥6m 81 15.1 8.0 54.4 83.5 Second-line treatment I+C 87 9.3 4.2 16.9 54.2 I+C+A 130 11.5 5.2 26.7 57.5 Second-line treatment cycle ≤3 97 7.4 2.9 4.8 31.0 ＞3 120 13.1 6.2 35.3 73.9
Exploring the role of bispecific and CAR-T cell therapies in gastric cancer: A systematic review and meta-analysis.
Authors: Moazzam Shahzad, Ahmad Basharat, Sohaib Irfan, Jawad Noor, Muftah Mahmud, Muftah Mahmud, Waleed Mir, Ghulam Mujtaba, Muhammad Fareed Khalid, Sarmad Zaman Warraich, Michael Vishal Jaglal
Journal: Journal of Clinical Oncology (2025)

465 Background: Gastric cancer (GC) is associated with significant mortality due to the limited efficacy of current conventional treatments, necessitating the need for novel therapies. In this systematic review and meta-analysis, we aim to explore the potential role and outcomes of bi-specific antibodies and chimeric antigen receptor T-cell (CAR-T) immunotherapy in treating GC. Methods: Using PRISMA guidelines, searches were conducted on PubMed, Cochrane, and Clinicaltrial.gov for 'Gastric cancers', 'bispecific antibodies', and 'CAR-T therapy' as of March 30, 2024. Out of 35 studies, 9 were selected for pooled analysis in R (v4.3.3) using the Der Simonian-Laird Estimator, calculating inter-study variance and extracting data with 95% CI. Results: 138 gastric cancer (GC) patients from 2 phase I (22.22%), 3 phase Ib (33.33%), 3 phase II (33.33%), and 1 case report (11.11%). Median age was 57 (28-77) years, and 76% (31/41) were male. Bispecific antibodies were MCLA-128 (25/138), catumaxomab (15/138), AK104 PD-1/CTLA-4 (16/138), ABL 001 DLL4VEGFA (19/138), and KN026 (25/138) while CART therapy was CT041 (38/138). The pooled overall response (OR), partial response (PR), and complete response (CR) for bispecific antibodies was 37% (95% CI, 0.12-0.71, I2=76%, n=100, p &lt;0.01), 21% (95% CI,0.05-0.55, I2=73%, n=85, p&lt;0.01), and 11%(95% CI, 0.02-0.38, I2=63%, n=85, p=0.03) respectively, while the pooled OR, PR, and CR for CART was 56% (95% CI, 0.40-0.71, I2=0%, n=38, p=0.41), 53%(95% CI, 0.36-0.69, I2=0%, n=38, p=0.38, ), and 12% (95% CI, 0.02-0.42, I2=38%, n=38 p=0.2), respectively. The pooled disease control rate was 75% (95%CI,0.46-0.92, I2=79%, n=80, p &lt; 0.01) for bispecific antibodies and 27% (95% CI,0.16-0.40, I2=0%, n=65, p=0.37) had the stable disease while pooled incidence of progressive disease was 18% (95% CI,0.09-0.31, I2=0%, n=55, p=0.53). The median progressive free survival was 6.74 months, with a median overall survival of 14.75 months. Common adverse effects included anemia, diarrhea, fatigue, and cytokine release syndrome grades 1 or 2. Conclusions: This analysis shows promising results in GC patients using bi-specific antibodies and CAR-T cell therapy. However, further clinical trials are needed to fully explore their potential.
Survival associated with metastatic early-onset colorectal cancer among Black patients: A real-world account.
Authors: Sepideh Mehravar, Amit Mahipal, Sakti Chakrabarti
Journal: Journal of Clinical Oncology (2025)

39 Background: Early-onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) diagnosed under the age of 50, is a growing health concern. The current study explored the racial differences in EOCRC survival in the United States (US). Methods: This retrospective cohort study was conducted using the TriNetX database, a platform that provides access to deidentified medical records on more than 130 million patients across 94 healthcare organizations in the US. The study cohort included patients with metastatic CRC (mCRC), aged 20 to 50, diagnosed between January 1, 2002, and January 1, 2020, and received frontline chemotherapy with oxaliplatin and 5- fluorouracil or capecitabine. The cohort was divided into Black or African American cohort and White cohort. The primary endpoint, 5-year overall survival (OS), was compared between these cohorts after performing 1:1 propensity score matching (PSM) for baseline demographics and comorbid conditions (Table). Kaplan-Meier curves, log-rank chi-square statistics, and hazard ratios (HR) were used to compare the outcome. Results: The entire cohort consisted of 2,923 patients with a mean age of 44 (±6) years; 48.58% were female. The majority were white (56.38%), followed by 15.56% of unknown race, Black/African American (9.16%), Hispanic (9.34%), and Asian (8.96%). After propensity score matching (PSM), there were 262 patients in both the Black and White groups. In the matched population, the Kaplan-Meier survival curves showed that Black patients had significantly lower 5-year OS rates (24.84%) compared to White patients (33.76%) [Hazard Ratio (HR): 1.39, 95% CI (1.06, 1.85), p&lt;0.05]. There is no significant difference between Black and White population over age of 50 [ HR: 1.06, 95% CI (0.966-1.179), P=0.2]. Conclusions: Survival among Black patients with EOCRC appears to be worse than White patients despite adjustment for confounding variables, supporting further research focusing onto this patient population. Characteristics of the cohorts before and after matching. Black cohort (n = 265) and White cohort (n = 1,632) characteristics before propensity score matching Black cohort (n = 262) and White cohort (n = 262) characteristics after propensity score matching Black patients, n (%) White patients, n (%) Sth diff. Black Patients, n (%) White patients, n (%) Sth diff. Age (Mean ± SD) 36.2 ± 6.18 36.3 ± 6.01 0.022 36.1 ± 6.17 36.2 ± 6.43 0.013 Female 144 (54.5%) 774 (47.4%) 0.142 143 (54.5%) 143 (54.5%) &lt;0.0001 Tobacco use 15 (5.6%) 96 (5.8%) 0.0087 15 (5.7%) 11 (4.2%) 0.0703 Hypertensive diseases 67 (25.3%) 214 (13.12%) 0.3147 65 (24.8%) 64 (24.4%) 0.0089 Ischemic heart diseases 10 (3.7%) 40 (2.4%) 0.0769 10 (3.8%) 10 (3.8%) &lt; 0.0001 Type 2 diabetes mellitus 24 (9%) 89 (5.4%) 0.1403 22 (8.3%) 19 (7.2%) 0.0426 Diseases of arteries, arterioles and capillaries 12 (4.5%) 47 (2.8%) 0.0881 11 (4.1%) 10 (3.8%) 0.0195
Rates and risk factors for recurrence of hepatocellular carcinoma after initial complete remission in response to transcatheter arterial chemoembolization: A systematic review and meta-analysis.
Authors: Aishwarya Thakurdesai, Sushrut Ingawale, David Liu, Tanmay Gandhi, Shefali Mody, Ansley Stuart, Babu Mohan, Ashutosh Barve
Journal: Journal of Clinical Oncology (2025)

612 Background: Transcatheter arterial chemoembolization (TACE) is used for palliative treatment of patients with inoperable hepatocellular carcinoma (HCC). Despite remarkable initial remission rates, frequent recurrences of HCC after TACE have resulted in questionable survival benefit. Our investigation aimed to study the rates and risk factors for HCC recurrence following remission after TACE. Methods: Comprehensive search of 5 databases (EMBASE, Web of Science, PubMed, CINAHL, ClinicalTrials.gov) was conducted to yield 4263 studies, which were screened based on prespecified inclusion and exclusion criteria. Outcomes assessed were total recurrence rate; 6-month, 1, 2, and 3-year cumulative recurrence rates; and 1 and 3-year survival rates for patients with and without recurrence. Meta-analysis was conducted by the random-effects model and heterogeneity was assessed by the I 2 statistic and 95% prediction interval. Systematic review of risk factors for recurrence was performed. Results: Twelve studies and 1,152 patients who underwent complete remission in response to TACE were included. The pooled rate of total recurrence was 60% (95% CI 53-67%). The pooled 6-month, 1-year, 2-year, and 3-year cumulative recurrence rates were 26% (95% CI 18-33%), 33% (95% CI 22-43%), 49% (95% CI 34-64%), and 62% (95% CI 53-71%), respectively. The pooled 1-year survival rates for patients with and without recurrence were 94% (95% CI 89-99%) and 99% (95% CI 99-100%), respectively. The pooled 3-year survival rates for patients with and without recurrence were 61% (95% CI 31-90%) and 91% (95% CI 81-100%). Heterogeneity was considerable based on the 95% prediction interval. Predominant risk factors for recurrence were larger tumor size, multinodularity, portal vein thrombosis, and higher AFP levels. Conclusions: HCC frequently recurs after initial remission achieved through TACE, with differences in survival rates between patients with and without recurrence. Identifying high-risk patients based on tumor size, multinodularity, portal vein thrombosis, and AFP levels could improve long-term outcomes.
Incidence of mediastinal lymph node positivity in patients undergoing robotic transthoracic esophagectomy.
Authors: Kenneth Lee Meredith, Jamie Huston, Ravi Shridhar
Journal: Journal of Clinical Oncology (2025)

379 Background: Esophageal cancer is increasing in incidence worldwide. Robotic approaches have quickly become mainstream due to the improved visualization and possible increase in nodal harvest. There remains significant debate on the utility of mediastinal lymph node dissection in esophageal cancer patients. We sought to analyze the incidence of mediastinal lymph node positivity and to evaluate its impact on survival in patients with esophageal cancer undergoing robotic assisted trans-thoracic esophagectomy (RATE). Methods: Utilizing a prospectively maintained esophageal database, we identified patients who were diagnosed with EC and underwent RATE between 2009-2024. We then identified patients with positive lymph nodes and stratified by location (celiac or mediastinal). Baseline univariate comparisons were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis tests. Pearson’s Chi-square test was used to compare categorical variables. Survival analysis was performed via Kaplain-Meier method. Results: We identified 201 patients who underwent RATE with a median age of 70 (41-91). There were 160 (79.6%) males and 41 (20.4%) females. The mean BMI was 26.5 ± 5.5 and mean ASA score was 3.1 ± 0.6. Adenocarcinoma was the predominate histology at 162(80.6%). Locally advanced T3/T4 tumors were identified in 53 (26.4%) patients and 63(31.3%) had clinical node + disease. Neoadjuvant therapy was utilized in 159(79.1%) patients. The median lymph nodes resected 18 (14 – 22), and length of hospitalization 8 (7 – 11) days. The 30 and 90-day mortality were 2.2% and 2.6% respectively. R0 resections was performed in 200 (99.5%) of patients and the pathologic complete response rates were 42.1%. The incidence of mediastinal lymph node positivewas 6.3% vs 76.3% abdominal. There were 17.6% of patients that had both mediastinal and abdominal lymph nodes positive. The median survival was 23 months for abdominal LN+, 19.5 months for mediastinal LN+ p=0.23. Multivariate analysis revealed that age, neoadjuvant radiation, nodal positivity were predictors of survival. Conclusions: The incidence of mediastinal positive lymph nodes are much higher than previously reported. Perhaps the improved visualization and manipulation of tissue with robotic approaches have enhanced our ability to resect these nodes. Mediastinal lymph node positivity is a poor prognostic factor for survival in patients undergoing robotic esophagectomy. Given these findings, we would continue to support aggressive nodal resection in patients diagnosed with esophageal cancer.
Efficacy and safety of intraperitoneal paclitaxel based regimens in patients with gastric cancer and peritoneal metastasis: A systematic review and meta-analysis.
Authors: Muhammad Bakhtiar, Nosakhare Paul Ilerhunmwuwa, Rabeea Ahmed, Mahnoor Mahnoor, Ahmad Ismail, Ibrahim Halil Sahin, Anwaar Saeed
Journal: Journal of Clinical Oncology (2025)

373 Background: Peritoneal metastasis (PM) occurs in about 5% - 20% of patients with gastric cancer (GC) at the time of diagnosis, and prognosis remains poor with limited treatment options. There are conflicting results on the efficacy of intra-peritoneal (IP) paclitaxel in patients with gastric cancer with PM. We performed a meta-analysis to examine the current evidence on the effectiveness of IP paclitaxel-based regimens in this patient population. Methods: A comprehensive search was conducted across Pubmed, EMBASE, Cochrane library, and Clinicaltrials.gov, resulting in the initial identification of 253 articles. Following screening, 35 articles, comprising only clinical trials (CT) and Randomized Controlled Trials (RCTs), were selected for detailed analysis. Screening and data extraction were conducted by two reviewers concurrently, with quality assessment performed using RoB (Risk of Bias) 2.0 tool and NIH quality assessment questionnaire. Proportional meta-analysis was done to estimate the pooled efficacy of IP paclitaxel based on the Median Survival Time (MST) and 1-year Overall Survival (OS), and tumor response was assessed using RECIST criteria. Subgroup analysis was conducted for patients who underwent conversion gastrectomy. Safety was assessed through the analysis of adverse events. Results: A total of 855 patients were included in the evaluation of MST, revealing an overall pooled MST of 20.21 months for GC patients with PM treated with IP paclitaxel-based regimens. Additionally, 1-year OS data was available for 785 patients, revealing an overall cumulative 1-year OS of 71% (95% CI: 66-76). Furthermore, among the 332 patients who underwent conversion gastrectomy, the pooled overall MST was 27 months. For 168 participants who underwent conversion gastrectomy after receiving therapy with IP PAC-based regimens, the 1-year OS was 84% (95% CI: 77-89). The most common adverse events (AE) observed were alopecia (75%) and anemia (60%). Overall, most studies exhibited low RoB, with only a few demonstrating poor quality. Conclusions: IP paclitaxel-based regimens demonstrate both safety and encouraging efficacy in the treatment of GC patients with PM. Subsequent conversion gastrectomy in eligible patients can further improve the survival outcomes.