tbuckley/cabot-search huggingface dataset:
EQUITY GI: A prospective study to enhance quality, inclusivity, and trial participation in Black patients with gastrointestinal cancer.
Authors: Sakti Chakrabarti, Navid Sadri, Melissa Amy Lumish, David L. Bajor, Madison Conces, J. Eva Selfridge, Pingfu Fu, Amit Mahipal
Journal: Journal of Clinical Oncology (2025)

TPS843 Background: Black individuals, including African Americans, experience a disproportionate cancer burden and exhibit the lowest survival rates among all racial groups for gastrointestinal (GI) cancers. The EQUITY GI study seeks to address the significant health disparities encountered by Black patients with GI cancers in the areas of biomarker testing, evidence-based care, clinical trial participation, and health literacy. Our central hypothesis postulates that a comprehensive approach—encompassing appropriate biomarker testing, ensuring evidence-based treatments, support for clinical trial participation, and health literacy initiatives—is essential to effectively mitigate health disparities among Black patients with GI cancers. Methods: The primary objective of this study is to promote equitable care for Black patients with GI cancers by ensuring appropriate biomarker testing and the delivery of evidence-based care. The secondary objectives include promoting clinical trial participation and enhancing health literacy. The specific goals are to increase the rate of evidence-based care, including biomarker testing, to ≥80%, increase the clinical trial enrollment rate from 5% to 15%, and improve the Cancer Health Literacy Test-30 (CHLT-30) score by 30%. Following a comprehensive assessment of the care gap, several initiatives will be implemented: 1. Tracking biomarker testing through a clinical information tracking tool (EQUITY-GI Oncotracker), 2. Providing guidance to treating providers through a molecular tumor board, 3. Facilitating referrals for clinical trials through navigators, and 4. Implementing health literacy interventions measured by CHLT-30 score. We aim to enroll 200 patients over 18 months. With this expected enrollment, the power to detect a ≥60% absolute improvement in the biomarker testing rate (from the current 20% to the expected ≥80%) is over 98%, using a two-sided chi-square test with a significance level of 0.05. To demonstrate an improvement in the clinical trial enrollment rate from 5% to 15%, 18 black patient will be required to get enrolled in a clinical trial through the referrals generated from the current project. To detect a 30% improvement in the mean CHLT-30 score (17 to 22) following health literacy interventions, at least 120 patients will be required, using a two-sided paired t-test with a significance level of 0.05.
Characterization of the tumor immune microenvironment (TIME) and somatic landscape in gastrointestinal (GI) malignancies with <i>MTAP</i> deletions (del).
Authors: Jun Gong, Kristen Keon Ciombor, Jennifer Brooke Valerin, Minxuan Huang, Edward Williams, Melissa Conrad Stoppler, Jacob Mercer, John H Strickler
Journal: Journal of Clinical Oncology (2025)

835 Background: PRMT5 is a synthetic lethality target in patients (pts) with MTAP del and early phase trials are underway with PRMT5 inhibitors. Additionally, MTAP del are associated with a less immunogenic TIME and reduced efficacy of immunotherapy, but research has primarily not been focused on GI malignancies. Thus, we investigated the TIME and somatic landscape in GI malignancies with MTAP del. Methods: From the Tempus Database, we retrospectively analyzed de-identified next-generation sequencing data from pts across GI malignancies, including pancreatic (n=11,217), gastroesophageal (GEJ, n=5,803), cholangiocarcinoma (CCA, n=3,244), and colorectal (CRC, n=17,537) cancers. Tumors were sequenced with the Tempus xT DNA (648-gene panel) and xR RNA assays. MTAP del were defined as two-copy losses. Somatic alterations (alt), immune cell infiltration predicted from gene expression patterns, PD-L1 from IHC, TMB, and MSI were evaluated. Chi-squared/Fisher’s Exact tests or Kruskal-Wallis tests were used to assess statistical significance (p&lt;0.05, q&lt;0.05 for false discovery rate correction for multiple testing). Results: MTAP del were identified in 14.8%, 11.3%, 0.9%, and 7.3% of pancreatic, CCA, CRC, and GEJ cancers, respectively. Of these, 98/93%, 99/91%, 92/89%, and 98/89% had co-occurring CDKN2A/B loss. In pancreatic, CCA, and CRC pts, MTAP del was associated with a reduced proportion of B cells and CD4 T cells, and there were higher percentages of macrophages vs pts with MTAP WT status (p&lt;0.001 for all). Reductions in proportion of CD8 T cells were also associated with MTAP del in pancreatic and CCA pts (p&lt;0.001 for both). Lower TMB (p=0.036) and MSI-H status (p=0.009) were found in CRC pts with MTAP del. GEJ with MTAP del also exhibited significantly lower MSI-H status than MTAP WT GEJ (p=0.014). SMAD4 alterations , a marker of reduced immune infiltrates, were more prevalent in pts with MTAP del across GI malignancies (q&lt;0.005). In the CCA cohort, there was a higher percentage of BRAF alt and FGFR2 fusions in pts with MTAP loss (q&lt;0.001, q=0.028), while KRAS alt were higher in pancreatic cases with MTAP loss (q&lt;0.001). Conclusions: This is the largest analysis of the TIME and somatic landscape of MTAP loss across GI malignancies. In pts with MTAP del and pancreatic cancer, CCA, and CRC, we observed a less immunogenic TIME pattern, indicating the evaluation of immunotherapy implications in these GI malignancies with MTAP del is warranted. Our findings are hypothesis-generating, providing further rationale to study synthetic lethality and novel combinatorial therapeutic strategies in GI malignancies with MTAP del.
Challenges in patient selection for surgical options in V600E BRAF–mutated metastatic colorectal cancer.
Authors: Giulia Maddalena, Eleonora Perissinotto, Rossana Intini, Van K. Morris, Francesca Bergamo, Timothy E. Newhook, Sara Lonardi, Scott Kopetz
Journal: Journal of Clinical Oncology (2025)

280 Background: V600E BRAF mutated metastatic colorectal cancer (mCRC), which represents almost 10% of mCRC, is associated with a decreased disease-free interval and increased risk of recurrence compared to other mCRC molecular subtypes; however, data show wide outcome heterogeneity within this subgroup. Surgery is known to be associated with improved outcomes in patients with mCRC, particularly in those with liver-only disease. While many patients with V600E BRAF have very aggressive disease and never have the chance to undergo surgery, it is not clear how to navigate the clinical heterogeneity and choose patients that might benefit the most from loco-regional treatment. Methods: We retrospectively evaluated V600E BRAF mutated mCRC patients from two independent high-volume institutions (MDACC and IOV IRCCS) who underwent metastectomy from Oct 2009 to Oct 2023. Patients with MSI-H disease and those who had R2 surgery were excluded. Clinicopathological features, such as sex, age, histology, radicality and site of surgery, were collected from institutional datasets. Relapse free survival (RFS) was defined as the time from surgery to first relapse or progression. Overall survival (OS) was defined as the time from surgery to the date of death or last follow up. Survival was estimated with the Kaplan Meier method, and the Cox proportional Hazard model was adopted for survival comparison. Results: We collected data from 71 V600E BRAF mutated mCRC patients (N=37 MDACC, N=34 IOV IRCCS); 49% were female, 61% had right-sided primary tumor and 62% had synchronous metastatic disease. Median age at metastatic disease diagnosis was 62 years old (IQR: 61-28). For 52% of patients, surgery was performed on liver-only disease; 35% involved the peritoneum. There were no emergency interventions. Median RFS was 7.9 months (95% CI: 5.4 – 10.5) and median OS was 39 months (95% CI: 28.8 – 51.7). No clinicopathological features, including sex, sidedness, histology, differentiation, presentation (synchronous, oligometastatic), or site of intervention, were associated with RFS. However, radicality (R1) was associated with worse RFS (HR=3.5 [95% CI: 1.8 – 6.5], p=0.0003) and OS (HR=2.7 [95%CI: 1.3 – 5.6], p=0.0122). Conclusions: In this retrospective evaluation of patients with V600E BRAF mutated mCRC who underwent metastectomy, only surgical radicality, observed in the post-operative setting, was associated with recurrence and survival outcomes. Therefore, while surgery should be evaluated whenever radical resection is feasible, the identification of patients with V600E BRAF mutated mCRC who might benefit the most from metastasectomy during pre-operative prognosis evaluation remains challenging.
Efficacy and safety of surufatinib in unresectable or metastatic grade 3 pancreatic neuroendocrine tumors (NET G3): Real-world analysis.
Authors: Jian Wang, Yun Liang, Jiang Long, Yihebali Chi, Suzhen Zhang, Yinying Wu, Yu Wang, Chunmei Bai, Weiyu Hu, Hanguang Hu, Lin Zhang, Jie Chen, Jing Hao
Journal: Journal of Clinical Oncology (2025)

657 Background: Currently, there is limited exploration regarding the treatment of NET G3, resulting in restricted treatment options. Therapeutics for NET G1/2 may serve as an alternative. Surufatinib, with its potent targeting of VEGFRs, FGFR1, and CSF-1R, not only exerts inhibitory effects on tumor angiogenesis but also modulates the immune microenvironment. Due to its demonstrated efficacy and manageable safety profile, it has secured approval for the treatment of G1/2 NETs. Methods: This is a multi-center real-world study that retrospectively analyzes the clinical data of pts with NET G3 who received surufatinib-based treatment from December 2021 to February 2024, aiming to assess its efficacy and safety. Eligible pts were unresectable or metastatic p-NET with ki-67&gt;20%. The primary endpoint was PFS, with secondary endpoints were ORR, DCR, and safety. Results: As of September 2024, data from 37 pts were analyzed. The median age was 54 years (range: 32-80), with 59.5% male. The median Ki-67 index was 30% (range: 25-70%), and 94.6% of the cases were non-functional p-NETs, with 89.2% having liver metastases and 35.1% having bone metastases. In terms of prior treatments, 18.9%, 40.5%, and 40.5% of pts had received 0, 1, and ≥2 systemic therapies, respectively. Among them, 81.1% had previously undergone chemotherapy, 35.1% had received interventional therapy of liver metastases, and 13.5% with everolimus or anti-angiogenic agents. 48.6% pts had surufatinib-based combination treatment. The median PFS was 9.30 months (mo, 95% CI: 8.02–13.02), with an ORR of 21.6% and a DCR of 81.1%. First-line (1L) treatment showed a higher ORR (42.9% vs. 16.7%) and a trend of better PFS (9.67 vs. 9.04 mo, p=0.7) compared to ≥2L treatment. Combination therapy improved ORR (33.3% vs. 10.5%) with a similar PFS (9.30 vs. 9.44 mo, p=0.93) compared to surufatinib monotherapy. Liver metastases had limited impact on PFS (9.93 vs 9.30 mo, p=0.55). Common grade ≥3 adverse events included hypertension (8.1%), proteinuria (5.4%), and elevated bilirubin (5.4%). Conclusions: Surufatinib has demonstrated initial efficacy and manageable safety in pts with NET G3, providing a new treatment option for these pts. First-line therapy may be a favorable factor for improving PFS. To delve deeper into these findings, additional subgroup analyses, with a particular emphasis on pts with ep-NET G3 will be conducted in the future.
A phase III study of combination therapy with everolimus plus lanreotide versus everolimus monotherapy for unresectable or recurrent gastroenteropancreatic neuroendocrine tumor (JCOG1901, STARTER-NET).
Authors: Susumu Hijioka, Yoshitaka Honma, Nozomu Machida, Nobumasa Mizuno, Tetsuya Hamaguchi, Narikazu Boku, Ryo Sadachi, Nobuyoshi Hiraoka, Takuji Okusaka, Hidekazu Hirano, Shogen Boku, Masafumi Ikeda, Satoshi Takeuchi, Noriyoshi Fukushima, Motohiro Kojima, Noriko Mitome, Yusuke Sano, Takaki Yoshikawa, Yukihide Kanemitsu, Makoto Ueno
Journal: Journal of Clinical Oncology (2025)

652 Background: There is limited evidence regarding the benefit of adding somatostatin analogs to molecular targeted agents for well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This phase III trial was conducted to compare everolimus plus lanreotide (EVE/LAN) with everolimus monotherapy (EVE) in patients with unresectable or recurrent GEP-NETs in the first-line setting. Methods: Patients with grade 1 or grade 2, nonfunctioning GEP-NETs with poor prognostic factors (Ki-67 labeling index (LI) 5-20% or diffuse liver metastases) were randomly assigned (1:1) to EVE (10 mg/day) or EVE/LAN (EVE + LAN 120 mg every 28 days). The primary endpoint was progression-free survival (PFS). The key secondary endpoint was overall survival (OS), and other secondary endpoints were objective response rate (ORR), disease control rate (DCR), and safety. The study was based on the hypothesis of an assumed median PFS of 11.0 months for EVE, expecting a 4-month improvement by EVE/LAN (HR: 0.73). The planned sample size was 250, requiring 195 events overall with a one-sided alpha level of 5%, a power of 70%, an accrual period of 5 years, and a follow-up period of 1.5 years. Results: Between April 2020 and June 2024, a total of 178 patients were enrolled, and the planned interim analysis was conducted in 145 patients (72 in the EVE and 73 in the EVE/LAN) in June 2024 with a data cut-off date of Nov 2023. The median PFS was 11.5 months in the EVE arm and 29.7 months in the EVE/LAN arm (HR 0.38 [99.91% CI 0.15–0.96], P = 0.00017 &lt; the prespecified significance level of 0.00046, by the stratified log-rank test). The HR for OS was 0.97 (95% CI: 0.24-3.90). The ORR and DCR were 8.7% (6/69) and 87.0% (60/69) in the EVE arm and 26.8% (19/71) and 91.5% (65/71) in the EVE/LAN arm, respectively. Both hematologic and non-hematologic toxicities tended to be more frequent in the EVE/LAN arm than in the EVE arm. No treatment-related deaths were observed in either arm. Based on the efficacy results, the Data and Safety Monitoring Committee recommended early termination of the study. Conclusions: The EVE/LAN provides statistically significant prolongation of PFS compared with EVE monotherapy, and the safety profile of EVE/LAN was manageable. The EVE/LAN might be a new standard treatment in the first-line setting for well-differentiated grade 1/2 GEP-NETs with poor prognostic factors. Clinical trial information: jRCT1031200023.
Clinical outcomes and changes in body composition following endoscopic submucosal dissection versus total gastrectomy in patients with proximal early gastric cancer.
Authors: Ga Hee Kim, Hyoung-Il Kim, Sung Hyun Park, Minah Cho, Da Hyun Jung, Yoo Min Kim, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Woo Jin Hyung, Yong Chan Lee
Journal: Journal of Clinical Oncology (2025)

415 Background: Sarcopenia is associated with poor surgical outcomes and prognosis in patients with gastric cancer. However, the relationship between changes in skeletal muscle following endoscopic submucosal dissection (ESD) versus total gastrectomy (TG) in patients with proximal early gastric cancer (EGC) remains unclear. This study aimed to investigate the clinical outcomes and skeletal muscle mass changes between ESD and TG in patients with proximal EGC. Methods: We retrospectively reviewed 329 patients who underwent either ESD (n=127) or TG (n=202) for cT1N0M0 gastric cancer in the upper third of the stomach between 2015 and 2019 at a tertiary care center. The skeletal muscle index (SMI), visceral/subcutaneous fat, and abdominal circumference were measured preoperatively, and at 1 and 3 years after surgery, using cross-sectional computed tomography. We compared these parameters between the two groups and assessed both short- and long-term outcomes, as well as prognostic factors. Results: No significant differences were observed between the two groups with respect to overall survival (P=0.266), recurrence-free survival (P=0.079), or disease-specific survival (P=0.24). The recurrence rate was four (3.1%) in the ESD group and two (0.9%) in the TG group. Of the four recurrences in the ESD group, two were cured by gastrectomy, and two by ESD. Two recurrences in the TG group died of cancer progression. In the ESD group, all deaths were unrelated to gastric cancer, compared to 83.3% in the TG group (P=0.376). Patients in the ESD group showed more preserved SMI (P&lt;0.001), visceral/subcutaneous fat (P&lt;0.001), and abdominal circumference (P&lt;0.001) at 1 and 3 years after surgery, compared to the TG group. The incidence of sarcopenia was significantly lower in the ESD group at postoperative years 1 (22.2% vs. 34.7%, P=0.02) and years 3 (25.7% vs. 40.6%, P=0.001). Sarcopenia had a significant impact on survival, with 5-year OS rates being lower in patients with preoperative sarcopenia (85.3% vs. 95.6%, P=0.005). Multivariate analysis revealed that the prognostic nutritional index was significantly associated with OS (hazard ratio, 0.86; 95% confidence interval: 0.75–0.99, P=0.03). Conclusions: Although OS was comparable between the ESD and TG groups, ESD was associated with better preservation of skeletal muscle and visceral/subcutaneous fat. These results suggest that ESD should be considered for patients with proximal EGC who are at high risk for sarcopenia.
Safety and efficacy of combining PD-L1 and CTLA-4 blockade with transarterial chemoembolization in intermediate-stage hepatocellular carcinoma: A phase II study.
Authors: Amy K. Kim, Mark Yarchoan, Marina Baretti, Paige Griffith, Won Jin Ho, Rose Parkinson, Ewa Kulikowicz, Yvette Cetasaan, Brad Wilt, Harry Luu, Hao Wang, Hyunsoo Song, Robert Liddell, Christos Georgiades, Kelvin Hong, Ana De Jesus Acosta
Journal: Journal of Clinical Oncology (2025)

609 Background: Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC) defined as Barcelona Clinic Liver Cancer (BCLC) B, but the benefit of adding systemic therapy remains unclear. While durvalumab and tremelimumab are approved for advanced HCC, the safety and efficacy in combination with TACE for intermediate-stage disease is undefined. Combining these PDL1 and CTLA4 inhibitors with TACE may enhance anti-tumor activity by leveraging TACE’s proinflammatory effects while blocking immune evasion and reducing immune suppression. This phase IIb study evaluates the safety and efficacy of this combination in BCLC-B HCC. Methods: We enrolled patients with intermediate-stage HCC that are also unresectable and ineligible for transplant. All patients received drug-eluting bead TACE (DEB-TACE) followed by durvalumab (1500 mg Q4W) and tremelimumab (300 mg once). Durvalumab monotherapy was continued until disease progression or unacceptable toxicity, for a maximum of 13 cycles. Primary endpoints include objective response rate (ORR) based on mRECIST. Secondary endpoints were overall survival (OS), and safety/adverse events (AEs). The trial is designed to rule out ORR of 30%. We obtained 3 serial biopsies and plasma for participating patients prior and one week after TACE and after the administration of immunotherapy for correlative studies. Results: 21 patients were enrolled. Of these, 20 patients were considered evaluable after receiving at least one dose of TACE and immunotherapy. ORR was 55% (95% CI: 32%-77%, CR 10% (n=2), PR 45% (n=9), meeting the primary endpoint. Five patients had PD (25%) per mRECIST, of which two were unconfirmed on repeat imaging and continued treatment beyond progression. Three patients received curative intent treatment as the result of treatment: surgical resection (n=1) and transplant (n=2). At a median follow-up of 18.4 months, median OS was 28.8 mo (95% CI: 15.1, NA) and mPFS was 6.1mo (95% CI: 3.3, NA). Grade 3 or higher immune related adverse events were rash (n=2), diarrhea, myalgia, nausea, elevated AST/ALT. One patient developed multiple irAEs after first dose (myocarditis, myositis, pericarditis) and was taken off study. Conclusions: The combination of DEB-TACE with PD-L1/CTLA-4 blockade is safe and shows promising activity in patients with BCLC-B HCC. The ongoing immune analysis and biomarker studies on serial blood and tissue biopsies will provide further insights into the mechanistic effects of this combination approach and inform future therapeutic strategies. Clinical trial information: NCT03638141 .
Impact of COVID-19 on colorectal cancer screening using Medicare Centers for Medicare and Medicaid Services (CMS) claims data.
Authors: Soyun Lim, Tae Hoon Lee, Sekwon Jang
Journal: Journal of Clinical Oncology (2025)

91 Background: When COVID-19 pandemic started in 2020 in the US, the Centers for Medicare and Medicaid Services (CMS) recommended that all non-urgent procedures, including screening colonoscopies, be delayed until pandemic stabilization. This was done to prevent the spread of the virus via colonoscopy since the presence of the virus in fecal samples has been reported in infected patients. Little is known of the impact of COVID-19 on the number of colorectal cancer (CRC) screening performed in the US. Methods: We utilized the Centers for Medicare &amp; Medicaid Services Database which provides Medicare claims data for 2013-2022. We searched “Medicare Physician &amp; Other Practitioners - by Geography and Service” using CPT code for colonoscopy(G0121, G0105), fecal occult blood test (FOBT; G0328, 82270), stool-based gene analysis (81528), sigmoidoscopy (G0104), and barium enema (G0120) and collected the number of CRC screening claims at national level and calculated the year-over-year (YOY) change. Results: The number of CRC screening claims in the US from 2013 to 2022 is listed (Table). The total number of CRC screening claims increased an average of 0.5% YOY from 2014 to 2019 then decreased 23.4% in 2020. From 2014 to 2019, the average YOY change in colonoscopy, FOBT, stool-based gene analysis, sigmoidoscopy, and barium enema claims were -0.5%, -6.0%, 58.7%, 8.1%, and -6.0%, respectively whereas in 2020, the rates were -27.5%, -25.0%, -14.4%, -25.3%, and -1.7%, respectively. The total number of CRC screening claims in year 2021 and 2022 increased from 2020, however, was still lower than 2019. Conclusions: CRC screening claims decreased in the US in 2020 likely due to COVID-19 and not yet returned to pre-pandemic levels. Number of CRC screening claims in the US from 2013 to 2022. Screening test 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 Colonoscopy 759,883 736,400 743,873 765,974 767,063 755,806 736,247 533,972 685,439 707,672 FOBT 1,307,054 1,263,602 1,161,214 1,130,130 1,085,777 996,016 897,993 673,614 646,550 556,950 Stool-Based Gene analysis 123,748 231,765 335,459 482,761 413,224 497,748 536,348 Sigmoidoscopy 2,666 2,316 3,254 3,390 3,835 3,784 3,975 2,968 3,893 3,680 Barium enema 107 93 80 116 128 97 58 57 44 65 Total CRC screening 2,069,710 2,002,411 1,908,421 2,023,358 2,088,568 2,091,162 2,121,034 1,623,835 1,833,674 1,804,715 Data are expressed in numbers (N). CRC; colorectal cancer; FOBT; fecal occult blood test.