tbuckley/cabot-search huggingface dataset:
Immune checkpoint inhibitors in digestive tumors with mismatch repair deficiency or microsatellite instability (dMMR/MSI-H): Effectiveness, safety, and prognostic factors in real-world practice.
Authors: Nieves Martinez Lago, Antia Cousillas Castiñeira, Pablo Jara-Martin, Margarita Reboredo, Paula Gonzalez Villarroel, Marta Covela, Carlos Lopez Lopez, Begona Graña Suarez, Elena Gallardo Martin, Juan De la Camara Gomez, Carme Garcia-Lorenzo, Alberto Carral Maseda, Martin Perez Martelo, Ana Fernandez Fernandez Montes, Fernando Rivera
Journal: Journal of Clinical Oncology (2025)

202 Background: ICIs have shown durable responses in dMMR/MSI-H digestive tumors in phase II-III clinical trials. The aim of this study is to evaluate the efficacy, safety and prognostic factors in the context of real-world practice. Methods: We conducted a retrospective multicenter observational study of patients with dMMR/MSI-H digestive tumors treated with ICIs in routine clinical practice across seven university hospitals in northwest Spain. We analyzed clinicopathological characteristics, treatment response data, efficacy, and adverse events. Results: A total of 122 patients treated with ICIs between November 2015 and February 2024 were included. The median age was 70.4 years (range 29-89), and 52.4% were male. The most frequent origin was colorectal (54.9%; 67.2% located in the right colon and 37.3% BRAF V600mt), followed by gastroesophageal adenocarcinoma (34.4%). 16.4% had &gt;3 metastatic sites (including 30.3% liver metastases and 44.3% peritoneal metastases). Baseline performance status (ECOG PS) was 0/1/2 in 21.7%/58.7%/19.8%, respectively. 39.3% had received one prior line of treatment. 92.6% received pembrolizumab monotherapy. The objective response rate (ORR) was 77.7% (including 31.3% complete response, 46.4% partial response, 13.4% stable disease, and 8.9% progressive disease), and the disease control rate (DCR) was 90.1%. Median overall survival (OS) was 53.2 months (95% CI: 42.6 – 63.7 months), and progression-free survival (PFS) was 46 months (95% CI: 30.6 – 61.4 months). The most common grade 3-4 treatment-related adverse events included nephritis (4.0%), hepatitis (3.3%), asthenia (2.5%), and pneumonitis (1.6%). 81.1% of patients discontinued treatment (including 24.6% due to progression, 21.3% after completing 2 years of treatment, and 14.8% due to toxicity). Potential prognostic factors identified in univariate analysis included ECOG PS, primary tumor resection, number of metastatic sites, and best treatment response. In multivariate analysis, a significant association was confirmed between ECOG PS, the presence of liver metastases, and best response to treatment with ICIs and overall survival. Conclusions: Our series confirms the efficacy and safety of ICIs in dMMR/MSI-H digestive tumors in routine clinical practice. The identified prognostic factors may be useful for identifying patients who could benefit the most from ICI treatment.
Efficacy and safety of trifluridine/tipiracil and bevacizumab (FTD/TPI+BEV) in patients with metastatic colorectal cancer (mCRC) in real-world practice.
Authors: Nieves Martinez Lago, Margarita Reboredo, Borja Gonzalez Gomez, Belén de Frutos González, Maria Carmen Riesco Martinez, Paula Carla Antonilli, Ana Lopez Alfonso, Elena Gallardo Martin, Ana Fernandez Fernandez Montes, Luis Cabezon-Gutierrez, Antia Cousillas Castiñeira, Reyes Ferreiro
Journal: Journal of Clinical Oncology (2025)

204 Background: In Sunlight trial, the combination of FTD/TPI + BEV showed a significant improvement in Overall Survival (OS) and Progression-Free Survival (PFS), along with better Objective Response Rate (ORR) and Disease Control Rate (DCR), compared to FTD/TPI alone, in patients with mCRC progressing after two chemotherapy regimens. The BeTAS trial aimed to evaluate the effectiveness and safety of the FTD/TPI + BEV combination in real-world practice. Methods: This was a retrospective, observational, multicenter study of mCRC patients treated with FTD/TPI+BEV in routine clinical practice across 11 Spanish university hospitals. It included patients with mCRC who were refractory or intolerant to standard therapies. Results: A total of 208 patients treated with FTD/TPI+BEV between July 2019 and December 2023 were included. The median age was 69 years (range 33 to 88 years), with 59.8% being male. 15.3% had an ECOG performance status of 2, 55.9% had RAS mutations, 30.3% had three or more metastatic sites, and 81.2% had liver metastases. Additionally, 19.8% had a time from diagnosis of first metastasis of less than 18 months, and 55.3% were categorized in Tabernero's Unfavorable Prognostic Subgroup. Most patients (81.3%) received FTD/TPI+BEV as third-line therapy, with 90.5% having previously received anti-VEGF therapy. The median number of treatment cycles was 4 (range 1 to 31 cycles). The ORR was 4.6%, and the DCR was 50%. The median PFS was 4.9 months (95% CI, 4.0-5.7 months), and the median OS was 11.1 months (95% CI, 9.5-12.8 months). The most common grade 3-4 toxicities included neutropenia (41.8%), asthenia (7.2%), and hepatic toxicity (5.5%). No treatment-related deaths were reported. Conclusions: Our series confirms the efficacy and safety of FTD/TPI + BEV in routine clinical practice, even in a population with poor prognosis and an extensive history of previous treatments.
Predictive role of circulating tumor DNA for locally advanced esophageal squamous cell carcinoma before surgery.
Authors: Ryota Kobayashi, Satoru Matsuda, Kohei Nakamura, Yuki Hoshi, Keiso Ho, Masashi Takeuchi, Kazumasa Fukuda, Rieko Nakamura, Hirofumi Kawakubo, Hiroshi Nishihara, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2025)

476 Background: A precise preoperative tumor monitoring method that reflects tumor burden during neoadjuvant treatment is required to guide individualized perioperative treatment strategies for esophageal squamous cell carcinoma (ESCC). This study examined the clinical significance of preoperative circulating tumor DNA (ctDNA) in the plasma of patients undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy. Methods: Plasma samples were collected longitudinally for ctDNA analysis as well as genomic DNA from primary lesions from patients with histologically confirmed ESCC who received neoadjuvant chemotherapy (NAC) followed by subtotal esophagectomy. Next-generation sequencing was used to identify mutations in both the plasma and primary tumors. We evaluated the relation ship between ctDNA alterations and recurrence in patients with locally advanced ESCC. Results: Pretreatment samples from 25 patients (100%) showed the same mutations in both ctDNA and primary tumors; therefore, they were classified as ctDNA-positive before treatment. In the cohort of 25 patients analyzed, those who tested positive for ctDNA after NAC had a significantly higher risk of recurrence; the 36-month recurrence-free survival rates were 92% for ctDNA-negative patients and 8% for ctDNA-positive patients (p &lt; 0.001). Conclusions: Preoperative ctDNA status may be a promising prognostic biomarker that can be assessed before surgery in patients with ESCC who received NAC. Expanded cohort validation will allow for more personalized multidisciplinary treatment approaches for ESCC tailored to ctDNA analysis.
A retrospective study of colorectal cancer CT imaging features involving microsatellite instability.
Authors: Scott McLaughlin, Jack Stearns, Albert Chiu, Samantha Hutzley, Tristan Kuckelman, Luke Kloft, Curt Bay, Madappa N. Kundranda, John Chang
Journal: Journal of Clinical Oncology (2025)

265 Background: This study aimed to identify correlations between CT imaging characteristics accessible to the radiologist with microsatellite instability (MSI) status among colorectal cancer. Noninvasive identification of MSI status can decrease time to treatment if pathology can be bypassed. Methods: 109 colorectal cancer patients were identified retrospectively from 2011 to 2018 with an average age of 61 years (58 male, 51 female) and had MSI pathological assessment. These subjects all had CT abdomen and pelvis obtained at the time of initial diagnosis. Imaging features of both the primary and metastatic lesions were assessed. Primary lesion features included: location, size, stage, attenuation compared to the liver, growth pattern, tumor margin, primary mass area, and the presence/absence of mesenteric infiltration. Metastatic lesion features included: size, attenuation relative to liver, and enhancement pattern. Patient age, sex, and tumor staging were obtained from patient medical records. Statistical analysis was performed using various methods, including chi-square, Mann-Whitney and Kruskal-Wallis tests. Results: 5 tumor characteristics displayed a statistically significant relationship with MSI status. MSI-H lesions were more likely to be clinical Stage 2, and MSI-L lesions were more likely to be Clinical Stage 3 (p=0.012). Tumors with distant metastasis were more likely MSI-L versus regional metastasis were more likely MSI-H (p&lt;0.001). Primary mass area was larger in the MSI-H than MSI-L group (p&lt;0.001). Tumors in the left colon are more likely to be MSI-L versus CRC tumors in the right colon are more likely to be MSI-H (p&lt;0.001). MSI-H tumors had a lower primary tumor Hounsfield Unit standard deviation (SD) than MSI-L tumors (p=0.002). The remaining features were not statistically significant. For primary lesion, these include mesenteric infiltration (p=0.189), tumor margin (p=1.000), enhancement pattern (p=0.498), growth pattern (p=0.127), tumor CT density (p=0.162), and liver density (p=0.105). Enhancement of metastasis also had no difference (p=0.376). Conclusions: Multiple CT imaging characteristics were predictive of MSI classification in CRC tumors, holding potential clinical relevance that can help guide individualized therapy. While these results were statistically significant, more research must be done to validate these findings and to derive useful nomograms.
Regorafenib combined with immunotherapy and prognosis of unresectable hepatocellular carcinoma.
Authors: Tianxiang Li, Jingyu Cao, Bing Han, Song Wang, Zixiang Li, Yuan Guo, Jinzhen Cai, Liqun Wu
Journal: Journal of Clinical Oncology (2025)

541 Background: To investigate the prognosis and influencing factors of patients with unresectable hepatocellular carcinoma (uHCC) receiving regorafenib in different treatment modes. Methods: A total of 227 patients with uHCC who received at least 2 cycles of regorafenib treatment in the Affiliated Hospital of Qingdao University between June 2018 and August 2022 were retrospectively collected through the Hospital Information System (HIS). 204 patients were finally enrolled by inclusion and exclusion criteria after screening. Results: The median follow-up was 25.9 (4.5-69.7) months. The median overall survival (OS) of 204 patients with uHCC was 27.7 (95%CI 21.98-33.42) months. The 1, 2, 3 and 5-year OS were 80.9%, 55.9%, 41.4% and 26.7%, respectively. Univariate analysis showed that combination with immune checkpoint inhibitor (ICI) and metabolic-associated complications were independent factors for survival benefit of regorafenib, while the Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) scale = 2, undecreased Alpha-fetoprotein (AFP), macrovascular invasion and extrahepatic metastasis were independent risk factors for poor prognosis (P&lt;0.05). Compared with 60 patients receiving regorafenib alone, 144 patients receiving regorafenib combined with ICI had a significant survival benefit (median OS, 16.9 vs. 31.5 months, respectively, P=0.006). The median OS of 153 patients receiving second-line therapy with regorafenib was 30.3 months. Among 51 patients receiving third or more lines of therapy with regorafenib, compared with 4 patients receiving regorafenib alone, 47 patients receiving regorafenib combined with ICI had a significant survival benefit (median OS, 9.4 vs. 24.1 months, respectively, P=0.000). Among 148 patients receiving local treatment, the median OS of patients with regorafenib combined with ICI (n=115) or without ICI (n=33) was 33.2 and 16.5 months, respectively (P=0.005). Conclusions: Regorafenib has a good prognosis in second-line treatment of uHCC. The OS of patients with regorafenib combined with ICI were significantly better than that of patients without ICI. The OS benefit of regorafenib combined with ICI was also equivalent in patients with third or more lines. The benefit of regorafenib combined with ICI was better for patients receiving local treatment.
Clinical outcomes of immunotherapy in metastatic pancreatic carcinoma: A systematic review and meta-analysis.
Authors: Moazzam Shahzad, Abhinav Vyas, Prashil Dave, Sohaib Irfan, Abat Khan, Ahtshamullah Chaudhry, Hana Qasim, Umair Khizer, Muhammad Fareed Khalid, Muhammad Shabbir, Michael Vishal Jaglal
Journal: Journal of Clinical Oncology (2025)

688 Background: Metastatic pancreatic carcinoma is one of the most challenging malignancies to treat. Traditional treatment modalities such as chemotherapy and radiation therapy have shown limited efficacy. This meta-analysis aims to investigate immunotherapy as a potential therapeutic option for metastatic pancreatic carcinoma. Methods: PubMed, Cochrane, Embase, and Clinicaltrials.gov were searched as per PRISMA guidelines. Data extraction was conducted independently by two reviewers, and any discrepancies were resolved through discussion. Pooled analysis was performed using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.16-2). Results: 834 patients from the 17 studies reporting immunotherapy outcomes in metastatic pancreatic carcinoma were included in this systematic review and meta-analysis. The studies included (There were) were 4 phase I (23.5%), 2 phase Ib (11.8%), 1 phase Ib/II (5.9%), and 5 phase II (29.4%), 1 retrospective study (5.9%) and 4 prospective studies (23.5%). The median age of the patients was 61 years and 55.6% (398/716) were male. Immunotherapies included were GVAX, tremelimumab, Mesothelin-specific Chimeric Antigen Receptor T cells, durvalumab, pembrolizumab, canerpaturev, Sotigalimab, nivolumab, CO-1.01, allogeneic natural killer cell immunotherapy, Anti-EGFR chimeric antigen receptor-modified T cells, bispecific antibody armed T cells, and clivatuzumab tetraxetan. The median follow-up duration was 17.8 months. The median overall survival was 7.9 months, and the median progressive-free survival was 4.6 months. The pooled overall response rate was calculated at 16% (95% CI 0.09-0.26, I2=70, p&lt;0.01, n= 426) and the pooled partial response rate was 13% (95% CI 0.09-0.26, I2= 67%, p&lt;0.01, n= 272). The pooled stable disease was calculated to be 28% (95% CI, 0.2-0.39, I2= 59%, p&lt;0.01, n=277). The pooled progressive disease was 36% (95% CI, 0.23-0.52, I2=34%, p=0.22, n=68). The most common overall adverse effects were anemia, diarrhea, and thrombocytopenia. Conclusions: This meta-analysis demonstrates that novel immunotherapies have promising results on metastatic pancreatic cancer. Future new clinical trials with a follow-up on current early-phase results are needed.
Transcriptomic features of Epstein-Barr virus-associated gastric cancer based on PD-L1 status.
Authors: Sun Young Rha, Woo Sun Kwon, Choong-kun Lee, Sejung Park, Zhong Wee Poh, Eunice Teo, Jingming Chew
Journal: Journal of Clinical Oncology (2025)

489 Background: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) accounts for 5-10% of all gastric cancers and has a relatively favorable prognosis compared to other subtypes. While the genomic profile of EBVaGC has been previously reported to exhibit extensive CpG island methylation, elevated levels of PD-L1/2, and an absence of TP53 mutations, transcriptomic features remain less explored. The response to immunotherapy of EBVaGC has been various. This study comprehensively investigates the transcriptomic characteristics of EBVaGC in relation to PD-L1 status. Methods: RNA sequencing was conducted on formalin-fixed, paraffin-embedded samples from 27 EBV-positive and 12 EBV-negative patients with HER2-negative gastric cancer. Gene expression was quantified using the RSEM package. Predict-IO, a machine learning-based predictive algorithm developed at Auristone Pte Ltd based on initial work done at the Genome Institute of Singapore (GIS), assessed the likelihood of a patient responding to immunotherapy based on transcriptome expression data. PD-L1 immunohistochemistry was performed using the 22C3 pharmDx assay, and status was classified by CPS. Results: A total of 200 differentially expressed genes (DEGs; log2FC &gt; 2, FDR &lt; 0.05) were identified in EBV-positive versus negative samples, with 157 genes down-regulated and 43 genes up-regulated. Upregulated genes included immune response related genes such as DMBT1, IDO1, PLA2G2A, and IL13RA2, while downregulated genes were primarily associated with cell adhesion, including LAMA1 and CCN6. In the EBV positive group, immune response pathways were enriched; however, within the PD-L1-Low group (CPS &lt; 1), activated signaling pathways such as MYC, E2F, and MTORC1 were observed. Conversely, the PD-L1-High group (CPS ≥ 5) exhibited upregulated snoRNAs. In the EBV negative group, the PD-L1-Low cohort displayed suppressed immune response and ECM remodeling factors, whereas the PD-L1-High cohort showed enrichment of ECM remodeling factors. The Predict-IO Score, which predicts immunotherapy response, was significantly higher in EBV-positive compared to EBV-negative samples ( p = 0.003), and scores were elevated in the PD-L1-High group compared to the PD-L1-Low group. Conclusions: In summary, EBVaGC includes subsets of different PD-L1 expression patterns with distinct activated signaling pathways, differences in ECM remodeling factors, and varying Predict-IO Scores. With these information, we could properly select the responsive patients to immunotherapy among EBVaGC.
Anlotinib plus benmelstobart as adjuvant therapy in patients with esophageal squamous cell carcinoma: A phase II clinical trial (ALTER-E005).
Authors: Changying Guo, Xiaobing Li, Shengjia Chen, Yongqiang Ye, Weimin Mao
Journal: Journal of Clinical Oncology (2025)

459 Background: Surgery represents a primary radical treatment for esophageal cancer, However, the risk of recurrence remains noteworthy after surgical resection, underscoring the need for more effective and tolerable postoperative regimens for esophageal squamous cell carcinoma (ESCC). Benmelstobart, a novel PD-L1 blockade, demonstrated promising antitumor activity when combined with anlotinib, an antiangiogenic agent, in the treatment of various tumors including advanced ESCC (NCT05038813) and biliary tract cancer (NCT03996408). Therefore, ALTER-E005 study aimed to evaluate the efficacy and safety of combining anlotinib with benmelstobart as adjuvant therapy in patients (pts) with ESCC. Methods: This was a single-arm, multi-center phase Ⅱ clinical trial. Thirty pts (≥18 years) with histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC who had undergone radical (R0) resection with no recurrence 6 to 12 weeks after surgery and an ECOG PS ≤ 1 were eligible for enrollment. Enrolled pts received oral anlotinib (12 mg, days 1-14) and intravenous benmelstobart (1200 mg, day 1) every 3 weeks for up to 16 cycles or until disease recurrence. The primary endpoint was disease recurrence free (DFS). while secondary endpoints included safety, 1-year DFS rate, 3-year DFS rate, 1- year overall survival (OS) rate, and 3-year OS rate. Results: As of the data cut-off date (September 20, 2024), a total of 30 patients were enrolled with a median age of 67. Among the 30 surgically resected patients with ESCC, 26 (86.7%) had an ECOG score of 1, and 25 (83.3%) were male. According to the eighth edition of the AJCC Cancer Staging Manual, 9 (30.0%) were classified as stage Ⅱ, and 21 (70.0%) were classified as stage Ⅲ. As of the data cut-off date, the median follow-up time was 8.9 months (95% CI: 7.9-12.3). Four pts experienced disease recurrence, and the median duration of DFS has not yet been reached, with 6-month and 1-year DFS rates of 95.7% (95% CI, 72.9%-99.4%), 84.0% (95% CI, 57.7%-94.6%) respectively. Currently, 13 pts are still undergoing therapy. Out of the total 30 patients, 9 (30%) experienced grade 3 treatment-emergent adverse events (TEAEs). No grade 4 or higher TEAEs were observed. The grade 3 TEAEs included hand-foot syndrome (10.0%), hypertension (3.3%), abnormal liver function (3.3%), immune-related hepatitis (3.3%), pneumonia (3.3%), hyperglycemia (3.3%) Lymphocyte count decreased (3.3%), acute cholecystitis (3.3%) and syncope (3.3%). Conclusions: This study highlighted the promising efficacy and safety preliminarily of combining anlotinib with benmelstobart as adjuvant therapy in patients with ESCC who underwent radical (R0) resection and showed no recurrence 6 to 12 weeks after surgery. Clinical trial information: NCT05252078 .
Relationship between PD-L1 expression and the number of biopsy specimens in advanced gastric cancer.
Authors: Taro Mizuno, Yukiya Narita, Yasunobu Ishizuka, Tomoki Sakakida, Kazunori Honda, Toshiki Masuishi, Hiroya Taniguchi, Shigenori Kadowaki, Masashi Ando, Masahiro Tajika, Kei Muro
Journal: Journal of Clinical Oncology (2025)

481 Background: Programmed cell death ligand 1 (PD-L1) expression shows spatial heterogeneity in gastric cancer. Compared with single biopsies, multiple biopsies may provide reliable PD-L1 expression results. However, the optimal number of biopsy specimens remains unclear. This study aimed to assess the relationship between PD-L1 expression and the number of biopsy specimens in advanced gastric cancer. Methods: We retrospectively analyzed patients with advanced gastric cancer who received first-line chemotherapy at a single institution between December 2021 and June 2024. Those in whom PD-L1 expression was evaluated using tumor-containing biopsy specimens were included. PD-L1 expression was measured using the Dako PD-L1 IHC 28-8 pharmDx assay. PD-L1 positivity was defined as a combined positive score of ≥5. The association between PD-L1 positivity and the number of biopsy specimens was tested using the chi-square or Fisher’s exact test. Results: Of the 183 patients screened, 110 were included. The patient characteristics were as follows: median age, 71 (range: 34–87) years; sex (male/female), 75/35; primary site (gastric/gastroesophageal junction), 102/8; and histological type (diffuse/intestinal/other), 59/34/17. The PD-L1 positivity prevalence was 71.8%. In 97 patients, human epidermal growth factor receptor 2 (HER2) expression was detected in the same specimens as PD-L1, with a HER2-positive rate of 14.4%. The mean numbers of biopsy and tumor-containing biopsy specimens were 5.14 (range: 2–10) and 4.25 (range: 1–10), respectively. The PD-L1 positivity prevalence was significantly higher when the number of biopsy specimens was ≥5 compared with ≤4 (77.5% vs 56.7%, P =0.03; Table). The same trend was observed according to the histological type (diffuse type, 75.0% vs. 46.7%, P =0.04; intestinal type, 79.2% vs. 60.0%, P =0.39). In HER2-negative cases, PD-L1 positivity was significantly more prevalent when the number of biopsy specimens was ≥5 compared with ≤4 (83.6% vs 54.5%, P =0.006; Table). However, there was no such difference in HER2-positive cases (54.4% vs 66.7%, P =1). Conclusions: The data suggest that collecting at least five biopsy specimens increases the likelihood of identifying PD-L1 positivity in advanced gastric cancer, particularly in HER2-negative cases. This approach may improve PD-L1 evaluation accuracy and lead to better treatment decisions. Relationship between the number of biopsy specimens and PD-L1 positivity. Number of biopsy specimens PD-L1 positivity (%) PD-L1 negativity (%) P value Overall 0.03 ≥5 77.5 22.5 ≤4 56.7 43.3 HER2-negative 0.006 ≥5 83.6 16.4 ≤4 54.5 45.5