tbuckley/cabot-search huggingface dataset:
Treatment patterns in patients with advanced gastrointestinal stromal tumor in Japan: An administrative claims database study.
Authors: Yoshito Komatsu, Yoichi Naito, Yuko Hirano, Yuji Kunitomi, Tsuyoshi Takahashi
Journal: Journal of Clinical Oncology (2025)

811 Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Tyrosine kinase inhibitors, including imatinib, sunitinib, and regorafenib, and the HSP90 inhibitor, pimitespib have been approved for advanced GIST in Japan, but few studies have examined the nationwide trend in treatment patterns. This study aimed to evaluate the real-world treatment patterns for advanced GIST in Japan. Methods: This retrospective cohort study used the Japanese hospital-based administrative claims database provided by Medical Data Vision Co., Ltd. (Tokyo, Japan). Patients diagnosed with advanced GIST according to ICD-10 codes who received any approved standard drug in Japan, such as imatinib, sunitinib, regorafenib, or pimitespib (Approved in June 2022) between July 2013 and March 2023 were included. The primary endpoint was the proportion of patients with GIST who were treated with each approved standard drug. Secondary endpoints included treatment patterns, time to treatment failure (TTF), overall survival, adverse events, and the proportion of patients who underwent surgical intervention for GIST while taking standard drugs. Results: This study included 2702 patients with advanced GIST. The median age was 70.0 years, 17% of the patients were ≥80 years, and 59% were male. The most common primary tumor sites were the stomach (37%), small intestine (25%) and large intestine (12%). The proportions of patients with GIST treated with imatinib, sunitinib, regorafenib, and pimitespib were 94% (2536 patients), 26% (702 patients), 14% (376 patients) and 1% (37 patients), respectively. The most common first-line regimen was imatinib (2485/2702 patients; 92%), second-line regimen was sunitinib (560/672 patients; 83%), third-line regimen was regorafenib (200/317 patients; 63%), and fourth-line regimen was imatinib (55/119 patients; 46%). The median TTF was 30.4 months (95% CI 27.4–32.9) with imatinib, 6.4 months (95% CI 5.6–7.7) with sunitinib, 5.2 months (95% CI 4.4–6.2) with regorafenib and 2.5 months (95% CI 1.7–3.1) with pimitespib. The proportions of patients who underwent surgical intervention for GIST was 15% (403/2702 patients), and curative surgery was 10% (273/2702 patients). Conclusions: This is the first real-world study to provide insights into the patient characteristics and current treatment patterns for advanced GIST in Japan. The treatment patterns are consistent with the Japanese Clinical Practice Guidelines.
Cost-effectiveness of blood-based colorectal cancer screening: A simulation model incorporating real-world longitudinal adherence.
Authors: Elifnur Yay Donderici, Shaun P. Forbes, Nicole Zhang, Greg Schafer, Victoria M. Raymond, Amar Das, Craig Eagle, AmirAli Talasaz, William M. Grady
Journal: Journal of Clinical Oncology (2025)

93 Background: Colorectal cancer (CRC) is a predominant cause of cancer-related mortality worldwide. Regular screening improves outcomes. However, despite there being many U.S. Preventive Services Task Force (USPSTF) recommended CRC screening options, many people elect not to use any of them. Most cost-effectiveness models assume perfect (100%) adherence initially and over time (longitudinally), which is implausible as approximately one-third of eligible individuals are not up to date with CRC screening. Our study evaluates the cost-effectiveness of Shield, an FDA-approved blood-based CRC test, while incorporating real-world adherence. Methods: The CAN-SCREEN (Colorectal cANcer SCReening Economics and adherENce) model is a validated, discrete-event simulation model designed to evaluate the clinical and economic outcomes of CRC screening strategies under real-world adherence scenarios. We simulated individual lifetime outcomes for a cohort of 10,000 people beginning screening at age 45, running 4,000 trials per cohort. We conducted a cost-effectiveness analysis using the CAN-SCREEN model, and compared the Shield blood-based test administered every three years to no screening. Costs were calculated from a healthcare perspective and adjusted to 2023 US dollars. Shield was considered cost-effective if the incremental cost-effectiveness ratio (ICER) was below $100,000 per quality-adjusted life-year (QALY) gained. The analysis also assessed the maximum price Shield could maintain while remaining cost-effective. Results: Compared to no screening, Shield increased the number of QALYs by 154 per 1,000 individuals and raised costs by $7.5 million per 1,000 individuals at its commercial test cost. With an incremental cost of $48,662 per QALY gained, Shield was found to be cost-effective relative to no screening at $100,000 cost per QALY willingness-to-pay threshold. Furthermore, the unit cost of Shield can be as high as $3,241 and $4,942 to be considered cost-effective at $100,000 and $150,000 per QALY gained, respectively. Conclusions: This study used the CAN-SCREEN model to compare Shield, an FDA-approved blood-based CRC screening test, against no screening, finding that Shield is cost-effective. With about one-third of the U.S. population not up to date on CRC screening, Shield's noninvasive approach offers a promising, cost-effective solution to increase adherence and reduce CRC mortality. Economic outcomes of Shield against no screening using CAN-SCREEN model. Intervention Test Unit Cost QALYs/Person Cost ($)/Person Cost ($)/QALY Gained vs No screening No Intervention - 15.269 $6,312.18 - Shield $1,495 15.423 $13,786.72 $48,662 Shield $3,241 15.423 $21,672.34 $100,000.00 Shield $4,942 15.423 $29,352.42 $150,000.00
FG-M108 plus capecitabine and oxaliplatin (CAPOX) for ﬁrst-line treatment of CLDN18.2+/HER2- advanced gastric/gastroesophageal junction adenocarcinoma (GC): Update results of a phase I/II trial to determine RP2D.
Authors: Jifang Gong, Funan Liu, Zhaoyu Jin, Miao Zhang, Shu Zhang, Yanqiao Zhang, Xinjun Liang, Yun Li, Yaping Yang, Lingyin Zhu, Lin Shen
Journal: Journal of Clinical Oncology (2025)

431 Background: There exists unmet need for previously untreated pts with CLDN18.2+/HER2- advanced GC. FG-M108, an mAb specifically targeting CLDN18.2 and exhibiting enhanced ADCC activity, has the potential to benefit these pts. Methods: This phase I/II trial evaluated safety, pharmacokinetics and preliminary antitumor activity of FG-M108 plus CAPOX in previously untreated pts with CLDN18.2+/HER2- advanced GC, where FG-M108 was administered intravenously at 300 mg/m 2 or 600 mg/m 2 Q3W. Here we compare results of FG-M108 at 300mg/m 2 (Cohort A) with 600mg/m 2 (Cohort B) to establish RP2D. Results: As of August 28, 2024, 63 pts with CLDN18.2+ (IHC 1/2/3+≥10%) GC were treated, 70% of whom had CLDN18.2 Medium-High expression (CMH, IHC 2/3+≥40%). Baseline characteristics were comparable between Cohorts A &amp; B. Increasing the FG-M108 dosage did not result in a higher incidence or severity of treatment-related adverse events (TRAE) overall. However, nausea and vomiting, identified as CLDN18.2 on-target toxicities, were significantly more frequent and severe in Cohort B compared to Cohort A.When 300 or 600 mg/m² of FG-M108 was administered intravenously Q3W, serum trough concentration exceeded the target drug concentration predicted by in vitro ADCC activity. The 300 mg/m² dose is expected to provide sufficient drug exposure as the effective dose.Moreover, in Cohort A, pts with CMH expression had a conﬁrmed ORR of 78% (unconﬁrmed ORR=81%) and a median PFS of 11.0 months（95%CI 6.9-12.7）, signiﬁcantly better than those in Cohort B. Based on safety, PK and efficacy trends, the RP2D was determined to be FG-M108 at 300mg/m 2 plus CAPOX. Conclusions: FG-M108 plus CAPOX had a manageable safety profile and promising antitumor activity in GC, with RP2D at 300mg/m 2 . A phase III trial is ongoing to confirm the efficacy of FG-M108 at 300mg/m 2 plus CAPOX as first-line treatment (NCT06177041). Clinical trial information: NCT04894825 . Cohort A n=52 Cohort B n=11 CMH % 71 64 Primary lesion-Stomach % 92 100 Metastatic organs ≥3 % 27 9 ORR/DCR with CMH % 81/97 57/86 PFS/DOR with CMH months 11.0/9.9 5.5/4.2 ≥G3 TRAE % 37 18 TRAE-Nausea % / ≥G3 Nausea % 38/2 64/9 TRAE-Vomiting % / ≥G3 Vomiting % 23/2 73/9
Comparative outcomes of neuroendocrine tumors in the historically underserved population of Bronx, NY: Montefiore Einstein Comprehensive Cancer Center.
Authors: Andrew Takchi, Ahan Bhatt, Carolina Bernabe, Prabhjot Singh Mundi, Chaoyuan Kuang, Fernand Bteich, Yvonne M. Saenger, Andreas Kaubisch, Bahar Laderian
Journal: Journal of Clinical Oncology (2025)

671 Background: Neuroendocrine tumors (NETs) pose different clinical implications based upon age at diagnosis, with regards to early-onset (EO&lt;50yrs) versus late-onset (LO&gt;=50yrs) disease. While primary-tumor resection is crucial for localized NETs, its benefit in metastatic cases without metastasectomy remains uncertain. This study examines variables associated with survival in EO versus LO cases, including primary tumor resection. Methods: A retrospective cohort of 91 patients with gastrointestinal(GI)-NETs were identified as part of an IRB-approved project. Disease-stage (local vs. metastatic), tumor grade (G1-3), 5-year-survival, primary-tumor removal, and race/ethnicity were included in this analysis. Results: Among all patients, 31.9% identified as Hispanic, 33% as non-Hispanic Black, 22% as non-Hispanic White, and 13.1% as other. Among all patients, 79 were classified as G1/G2. Among LO patients, 87.5% (n=63) were G1/G2, among which 46% (n=29) were metastatic. Among EO patients, 84% (n=16) were G1/G2, among which 68.8% (n=11) were metastatic. In the LO group with G1/G2 tumors, 5-year survival rate was 48.3% for metastatic disease and 58.8% for localized disease. For EO with G1/G2 tumors, the 5-year survival rate was 72.7% for metastatic disease and 80% for localized disease. In the EO G1/G2 group, 5 of the 11 patients with metastatic disease had primary tumor removal without metastasectomy with 100% 5-year survival rate. In the LO G1/G2 group, 7 of 29 metastatic patients had primary tumor removal without metastasectomy, with 86% 5-year survival rate. Resection of primary tumor (without metastasectomy) in patients with metastatic G1/G2 NETs was associated with improved 5-year survival, independent of age at diagnosis ( p-value =0.008), as shown in the table. Conclusions: This study helps to emphasize the importance of primary tumor removal in improving survival outcomes for patients with metastatic low-grade GI-NETs, regardless of age. Further investigation is warranted to study the role of certain imperative variables such as site of metastases, number of metastases, and patient co-morbidities. Survival outcomes based on primary tumor removal in metastatic low-grade GI-NETs. No 5-year survival 5-year survival Primary tumor removal without metastasectomy 1 11 No surgery 12 8
Investigation of synergistic effects in trials of combination therapies with immune-checkpoint inhibitors in advanced gastric or gastroesophageal junction cancer.
Authors: Jun Okui, Kengo Nagashima, Satoru Matsuda, Yasunori Sato, Hirofumi Kawakubo, Masashi Takeuchi, Kenro Hirata, Kai Tsugaru, Shun Yamamoto, Motoo Nomura, Takahiro Tsushima, Hiroya Takeuchi, Ken Kato, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2025)

405 Background: Combinations of immune checkpoint inhibitors (ICI) and chemotherapy (CT) have been approved for gastric cancer. However, there is a hypothesis that this combination may blunt antitumor immune responses because most chemotherapeutic agents also target lymphocytes. The primary objective was to investigate that the ICI and CT does not interfere each other’s therapeutic effects in advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC) patients. Methods: The reconstructed individual patient data was electronically extracted from the Kaplan-Meier curve of phase III randomized controlled trials (RCTs). The observed PFS curve of each constituent monotherapies was used to estimate simulated PFS curves expected under a model of independent drug action. If the observed curve demonstrated significantly better PFS than simulated curve, the combination of ICI and CT may have a synergistic effect, implying a superior outcome compared to simply adding the component monotherapy. Results: The study included 2,538 unresectable advanced, recurrent, or metastatic GC or GEJC patients from three RCTs comparing pembrolizumab (KEYNOTE-061, KEYNOTE-062 and KEYNOTE-859). In patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater, the 1-year and median PFS of the observed and simulated curves were 28.0% vs. 27.9%, and 6.89 months vs. 6.88 months, respectively. One sample log-rank test showed no significant differences between the observed and simulated curves (p = 0.107). In the subgroups with PD-L1 CPS ≥10 or &lt;1, the 1-year PFS of the observed and simulated curves was 34.7% vs 32.8%, and 28.5% vs 26.8%. Conclusions: The observed PFS of ICT involving pembrolizumab was comparable to the simulated PFS estimated from the data for each monotherapy regardless of the magnitude of PD-L1 CPS. Although it was not clear whether potential synergies existed for ICT, these findings at least suggest that the benefits of ICI and CT are not interfering each other, thereby providing theoretical support for the efficacy of ICT in patients with advanced GC or GEJC.
Blood TCTP as a biomarker associated with immunosuppressive features and resistance to immunotherapy in metastatic gastric cancer.
Authors: Hyung-Don Kim, Yeong Hak Bang, Jaewon Hyung, Changhoon Yoo, Myeong Jin Yoon, Hayoung Lee, Hyungsu Jeon, Hideyuki Yanai, Gwanghee Lee, Min-Hee Ryu
Journal: Journal of Clinical Oncology (2025)

474 Background: Cancer biomarkers are essential for determining the prognosis of the disease and/or predicting its response to specific treatments. However, established biomarkers representing specific myeloid cell populations and representative biomarkers in gastric cancer remain unavailable. Therefore, this study aimed to explore the prognostic and immunological relevance of plasma translationally controlled tumor protein (TCTP) in patients with advanced gastric cancer treated with immune checkpoint inhibitor (ICI) and cytotoxic chemotherapy. Methods: Plasma samples were prospectively collected from the cohorts of patients with gastric cancer who were treated with 1 st line fluoropyrimidine plus platinum chemotherapy (n = 143, cohort 1) and 3 rd line nivolumab (n = 165, cohort 2). Plasma TCTP levels were quantified using ELISA, and multiplex proteomic analysis (Olink) was conducted to assess expression levels of immune-related proteins. An external single-cell RNA sequencing (scRNA-seq) dataset was employed to validate the findings. Results: Patients with high plasma TCTP levels (TCTP-high group) exhibited poor survival outcomes with 1 st line chemotherapy compared to those with low levels (TCTP-low group) in cohort 1. In the TCTP-high group, proteins associated with immunosuppressive myeloid cells, angiogenesis, and immune exclusion of T/NK cell function were upregulated, whereas proteins involved in T-cell activation/exhaustion were significantly upregulated in the TCTP-low group. The scRNA-seq analyses of myeloid cells revealed that TCTP pathway-associated genes (i.e., TLR2 , CXCL1, and CXCL2 ) were specifically expressed in immunosuppressive APOE + macrophages, THBS1 + macrophages, and CD1C + conventional type 2 dendritic cells. In the TCTP-high group, patients treated with nivolumab (cohort 2) also experienced poor survival outcomes. Conclusions: Plasma TCTP is a readily measurable prognostic biomarker, reflecting immunosuppressive signals of myeloid cells in patients with gastric cancer treated with ICI and chemotherapy.
Robot-assisted esophagectomy with extended mediastinal lymph node dissection: The learning curve and surgical outcomes.
Authors: Hirofumi Kawakubo, Masashi Takeuchi, Satoru Matsuda, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2025)

457 Background: We have performed thoracoscopic surgery (TMIE) and robot-assisted surgery (RAMIE) for esophageal cancer with extensive mediastinal lymph node dissection, including resection of the sympathetic nerve layers and the thoracic duct. We studied the learning curve, short-term results, and mid-to-long-term outcomes of RAMIE for esophageal cancer at our institution. Methods: We compared surgical times at different stages of the procedure. For mid to long-term outcomes, we analyzed 360 cases of TMIE/RAMIE performed between January 2009 and June 2022, comparing the incidence of postoperative complications, recurrence-free survival, and patterns of recurrence between RAMIE and TMIE. Recurrent laryngeal nerve palsy (C-D I) was evaluated using postoperative endoscopy or contrast swallowing tests to assess even mild paralysis. Results: The average console time in the thoracic procedure was 234.4 minutes, with Group A (294.5 minutes, range: 211-397 minutes) showing significantly longer times compared to Group B (190.5 minutes, range: 130-257 minutes). Blood loss was almost 0ml in 10 cases (50%) in Group A and 25 cases (62.5%) in Group B. Postoperative complications included pneumonia in 5 cases (8.3%) and recurrent laryngeal nerve palsy (C-D III) in 5 cases (8.3%), with no significant difference between the groups. However, surgical time for lymph node dissection around the recurrent laryngeal nerve was significantly shorter in Group B compared to Group A. Long-term analysis included 326 TMIE and 34 RAMIE cases. Mild recurrent laryngeal nerve palsy (&gt;C-D I) was observed in 92 cases (28%) of TMIE and 7 cases (21%) of RAMIE, showing a lower tendency in the RAMIE group (p=0.338). Pneumonia (&gt;C-D II) occurred in 57 cases (18%) in the TMIE group and 3 cases (9%) in the RAMIE group, with a relatively lower incidence in the RAMIE group (p=0.178). For patients with cT1N0M0 who did not receive preoperative chemotherapy, the 3-year recurrence-free survival rates were 95% for TMIE and 93% for RAMIE. Conclusions: RAMIE demonstrated a significant reduction in operative time due to the standardization of the procedure, particularly in the dissection of recurrent laryngeal nerve lymph nodes and other upper mediastinal maneuvers. RAMIE also showed a potential reduction in the incidence of recurrent laryngeal nerve palsy and pneumonia compared to TMIE. In terms of long-term outcomes, RAMIE maintained local control similar to TMIE, with further improvements in safety expected.
A multicenter, open-label, first-in-human study of TYRA-200 in advanced intrahepatic cholangiocarcinoma and other solid tumors with activating <i>FGFR2</i> gene alterations (SURF201).
Authors: Jordi Rodon Ahnert, Sameek Roychowdhury, Haley Ellis, Fernando F. Blanco, Timothy Burn, Jennifer Michelle Davis, Alex Balcer, Alena Zalutskaya, Robin Kate Kelley
Journal: Journal of Clinical Oncology (2025)

TPS646 Background: Approved Fibroblast Growth Factor Receptor (FGFR) inhibitors have demonstrated clinical benefit in locally advanced or metastatic cholangiocarcinoma harboring oncogenic FGFR2 fusions or other rearrangements. However, the emergence of acquired resistance mutations limits the clinical activity and duration of responses to currently available inhibitors. TYRA-200 is an orally bioavailable FGFR1/2/3 inhibitor designed to specifically address these clinically observed acquired resistance alterations in FGFR2. Methods: SURF201 is a single arm, multicenter, open-label, first-in-human, dose escalation and expansion study designed to investigate TYRA-200 in patients (pts) with advanced intrahepatic cholangiocarcinoma and other solid tumors with primary activating FGFR2 gene alterations and on-target acquired known FGFR2 resistance mutations. The study is being conducted in two parts. Part A dose escalation uses an i3+3 design and is evaluating the safety, tolerability, and the pharmacokinetic profile of TYRA-200. Part B dose expansion will further characterize the safety profile and evaluate the preliminary anti-tumor activity of TYRA-200 by RECIST v1.1 in pts with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma who have previously received an FGFR inhibitor(s) and have developed acquired FGFR2 kinase domain resistance mutations. The study is currently planned for approximately four centers in the US and is actively enrolling (NCT06160752). Clinical trial information: NCT06160752 .
Definitive local therapy in solitary liver metastatic anal squamous cell carcinoma.
Authors: Teerada Siripoon, Conor O'Donnell, Michael H. Storandt, Patrick Starlinger, Nguyen H. Tran, Thomas D. Atwell, Krishan Jethwa, Zhaohui Jin
Journal: Journal of Clinical Oncology (2025)

5 Background: Metastatic anal squamous cell carcinoma is rare and associated with a poor prognosis. There is limited evidence on the impact of local interventions on survival outcomes in patients with metastatic disease. We aimed to evaluate the survival of patients with liver-only metastatic anal cancer following definitive local management of liver lesions. Methods: This is a single-institution retrospective cohort study of patients with liver-limited metastatic anal cancer who underwent curative-intent local therapy. Clinical characteristics were collected and analyzed. The Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival (OS). Prognostic factors associated with DFS and OS were assessed using Cox-proportional hazards models. Results: Twenty-five patients were included, median age was 59 years, and 92% were female. None of the patients had known HIV infection, 92% had HPV-positive disease and 76% had metachronous liver metastases following locoregional disease. All patients received chemoradiation for the primary lesion Unilobar hepatic involvement was present in 76% of the patients, with 56% having a single metastatic lesion. Pre-intervention systemic therapy was provided to 52% of the patients, including 8 who received carboplatin and paclitaxel, with a median duration of 3 months and ORR of 69%. Definitive treatment of metastatic disease included surgical resection (60%), non-surgical interventions (20%), and multimodal therapy (20%). All patients had viable tumor in the pathological specimen. With a median follow-up of 22 months, median DFS was 7.3 months, and median OS was 51.3 months. An ECOG performance status of 2, poorly differentiated histology, and extrahepatic recurrence were identified as significant prognostic factors in the univariate analysis, but not in the multivariate analysis. Conclusions: Our results demonstrate potential for long-term survival in liver-limited metastatic anal squamous cell carcinoma amenable to local therapeutic intervention combined with systemic therapy. These findings warrant further prospective study of local therapy in oligometastatic anal cancer. Characteristics N=25 (%) Median number of liver metastases (range), lesions- 1- 2-3- &gt;3 1 (1-20)14 (56)8 (32)3 (12) Median maximal diameter of liver metastases (range), cm 3 (0.9-11.9) Best response of liver metastases to chemotherapy (N=13)- Complete response- Partial response- Stable disease- Progressive disease 2 (15)7 (54)3 (23)1 (8) Surgical procedure (N=20)- Right/left hemi-hepatectomy- Segmentectomy- Wedge resection 4 (20)14 (70)2 (10) Non-surgical procedure (N=10)- Local ablation- Radiotherapy- Other 5 (50)3 (30)2 (20) Hepatic surgical margins (N=20)- Positive margins- Close margins (&lt;1mm)- Negative margins 02 (10)18 (90) Recurrent disease- Yeso Intrahepatico Extrahepatic- No 20 (80)14 (70)6 (30)5 (20)