tbuckley/cabot-search huggingface dataset:
TROP2 expression in small bowel adenocarcinoma: A potential target for novel therapeutic strategies.
Authors: Hiroyuki Fujii, Hirokazu Shoji, Hidekazu Hirano, Toshiharu Hirose, Natsuko Tsuda Okita, Atsuo Takashima, Ken Kato
Journal: Journal of Clinical Oncology (2025)

799 Background: Small bowel adenocarcinoma (SBA) is a rare cancer with limited chemotherapy options. To explore TROP2 as a potential therapeutic target for SBA and develop new treatment strategies, we examined TROP2 protein expression in SBA and analyzed associated clinicopathological features and prognosis, including PD-L1 expression levels in the same tumor samples from our previous studies. Methods: We retrospectively reviewed patients diagnosed with SBA who underwent adjuvant or palliative chemotherapy between July 2010 and July 2023 at our hospital. Immunohistochemistry staining of TROP2 (clone: SP295) was performed for pathological samples. The intensity of TROP2 membranous staining in tumor cells was classified as 0 (absent), 1 (weak to moderate), or 2 (strong). TROP2 positivity was defined as intensity 1 with ≥ 50% expression or intensity 2 with ≥ 10% expression. We also assessed overall survival (OS) in patients receiving palliative chemotherapy to examine the association between prognosis and TROP2, excluding microsatellite instability-high (MSI-H) patients treated with immunotherapy. Results: Pathological samples and clinical data were available for 51 patients. The median age was 63 years (range: 23–82), and 76% were male. Most patients (94%) had a performance status (PS) of 0–1. The primary lesion was in the duodenum in 49% of patients and in the jejunum or ileum in 51%. Surgery and adjuvant chemotherapy resulted in no recurrence in 12% of patients, while 88% received oxaliplatin-based palliative chemotherapy for unresectable SBA. Among those with unresectable SBA, 8% (4/51) had MSI-H and were treated with immunotherapy. TROP2 positivity was 84.3% (43/51). There were no differences in age, sex, or primary lesion between the TROP2-positive and TROP2-negative groups. In this cohort, the median CPS was 3 (range, 0–60). CPS was lower in TROP2-positive samples compared to negative samples (median CPS 7.9% vs. 23.4%, p = 0.030). However, all MSI-H cases were found to be TROP2-positive. Among patients receiving palliative chemotherapy, excluding those with MSI-H treated with immunotherapy, OS did not differ significantly between TROP2-positive and TROP2-negative patients (17.0 months vs. 9.2 months, HR 0.70, p = 0.480). Even after adjusting for age and PS, TROP2 expression was not identified as a prognostic factor. Conclusions: Our study highlighted that TROP2 is frequently expressed in SBA, suggesting it could be an effective therapeutic target for new treatment strategies. Further investigation is needed to confirm its potential.
Non-contrast MRI as a surveillance tool for recurrent hepatocellular carcinoma after curative treatment: A prospective multicenter intra-individual comparison trial.
Authors: Dong Ho Lee
Journal: Journal of Clinical Oncology (2025)

530 Background: Hepatocellular carcinoma (HCC) often recurs following curative treatment, significantly impacting long-term survival. Contrast-enhanced multiphasic computed tomography (CECT) is widely utilized for HCC recurrence surveillance but carries risks such as radiation exposure and adverse reactions to contrast agents. This prospective multicenter trial aimed to compare the accuracy of non-contrast abbreviated magnetic resonance imaging (NC-MRI) with CECT in detecting late recurrent HCC. Methods: This prospective multicenter intra-individual head-to-head comparison trial (study identifier: NCT05690451, KCT0006395) enrolled participants who had undergone curative treatment for HCC and remained recurrence-free for over two years. Participants underwent three rounds of surveillance at 2–6-month intervals using both CECT and NC-MRI. The primary outcome was the detection accuracy of each modality, compared using the McNemar test. Secondary outcomes included detection sensitivity and specificity. Results: A total of 203 participants underwent 528 rounds of paired CECT and NC-MRI, detecting recurrent HCC in 22 participants (10.8%). Among these cases, 21 showed intrahepatic recurrent HCC with a median tumor size of 1.3 cm, and one exhibited aortocaval lymph node metastasis. NC-MRI demonstrated a detection accuracy of 96.6% (196/203), significantly higher than CECT's 91.6% (186/203) (P=0.006). NC-MRI also exhibited significantly higher sensitivity in detecting recurrent HCC compared to CECT (77.3% [17/22] vs. 36.4% [8/22]; P=0.012), while specificity did not differ significantly between NC-MRI and CECT (98.9% [179/181] vs. 98.3% [178/181]; P=0.999). Conclusions: NC-MRI showed significantly higher sensitivity and accuracy in detecting recurrent HCC among patients who had been disease-free for more than two years after curative treatment, establishing it as the preferred surveillance modality for late recurrence. Clinical trial information: NCT05690451 . Contrast enhanced CT Non-contrast MRI Difference, % (95% CI) P-value Estimates, % (n/N) 95% CI, % Estimates, % (n/N) 95% CI, % Accuracy 91.6% (186/203) 87.8-95.5 96.6% (196/203) 94.0-99.1 4.9 (1.7, 8.2) 0.006 Sensitivity 36.4% (8/22) 14.5-58.2 77.3% (17/22) 58.3-96.3 40.9 (16.8, 65.0) 0.012 Specificity 98.3% (178/181) 96.5-100 98.9% (179/181) 97.4-100 0.6 (-0.5, 1.6) 0.999
Surgical treatment results for oligo-recurrence of gastric cancer.
Authors: Youjin JIN Jang
Journal: Journal of Clinical Oncology (2025)

462 Background: Despite advancements in diverse treatments, approximately 40-50% of advance gastric cancer patients experience recurrence even after curative resection surgery. The condition where there is a limited recurrence after the control of the primary tumor site is referred to as oligo-recurrence. However, there is scarce reporting on oligo-recurrence after gastric cancer surgery. This study compiled cases of patients who underwent surgery for recurrent gastric cancer after R0 surgery. Since there are no specific treatment guidelines for recurrence after gastric cancer surgery, this research could be beneficial in providing insights and assistance. Methods: This retrospective study includes data from 25 patients who underwent surgery for suspected oligo-recurrence of gastric cancer among those who had undergone surgery from June 2008 to May 2018. If a solitary mass suspected of recurrence is identified during surveillance, a PET-CT is performed. Patients with suspicion of peritoneal dissemination, carefully excluded through a multidisciplinary approach, are selectively omitted. All patients undergo excision surgery for both treatment and tissue examination purposes. Results: Out of 25 cases, there were 6 cases of paraaortic lymph node enlargement, 9 cases liver nodules, 8 case lung nodules, and 1 case tumor bed mass. In the postoperative tissue analysis, 4 cases of paraaortic lymph node enlargement, 5 cases of the liver nodules, and 1case tumor bed mass were confirmed to be recurrences of gastric cancer. All of lung nodule were diagnosed with lung cancer. All 10 cases underwent chemotherapy after metastatectomy. Among them, 3 cases experienced recurrence and died an average of 12.3 months after surgery. Seven cases did not experience recurrence and have survived with an average survival time of 102 months to date. Conclusions: The metastatectomy is safe and effective for patients with oligo-recurrence from GC and can improve their prognosis. For an accurate diagnosis, oligometastectomy is essential. However, our results need to be confirmed by more randomized controlled clinical studies. Treatment result after metastatectomy. Case Diagnosis Chemotherapy aftermetastatectomy Recurence after metastatectomy DFS after metastatectomy OS after metastatectomy OS after gastrectomy Status 1 LN metastasis 1/1 15cycles FOLFOX 147 147 156.4 ALIVE 2 LN metastasis 1/1 37cycles TAS-118 liver metastasis 22 40.6 74.9 DEATH 3 LN metastasis 1/3 12cycles FOLFOX 98.1 98.1 125.5 ALIVE 4 LN metastasis 1/1 35cycles FOLFOX 50.9 50.9 71.3 ALIVE 5 Liver metastasis ONO tiral Liver, bone mets. 3.73 27.9 64.6 DEATH 6 Liver metastasis 12cycles FOLFOX 68.3 68.3 122.2 ALIVE 7 Liver metastasis 12cycles FOLFOX 96 96 105.8 ALIVE 8 Liver metastasis 82cycles FOLFOX 55 55 77.4 ALIVE 9 Liver metastasis 12cycles FOLFOX 94.4 94.4 103.9 ALIVE 10 Tumor bed 12cycles FOLFOX 9 25.5 24.4 DEATH
Frequency and incidence of oncogenic <i>RAS</i> mutations in patients with metastatic pancreatic ductal adenocarcinoma: Derived from the real-world evidence database Foundation Medicine Insights.
Authors: Shubham Pant, Sumit Kar, Kevin K. Lin, Ethan Ahler
Journal: Journal of Clinical Oncology (2025)

777 Background: Approximately 60,000 patients are diagnosed with pancreatic cancer in the United States annually, with half of all cases diagnosed at the metastatic stage. 1 The most common type, pancreatic ductal adenocarcinoma (PDAC), accounts for ~90% of all pancreatic cancers 2 and is characterized by frequent KRAS oncogenic mutations. Newer investigational therapeutics target HRAS and NRAS, in addition to KRAS. To comprehensively characterize the incidence of RAS mutations in patients with PDAC, we analyzed mutational frequency data from the Foundation Medicine Insights (FMI) database. Methods: NGS-based comprehensive genomic profiling (CGP) data from 27,298 PDAC tissue samples were accessed from the FMI database (May 7, 2024 data cut). Only ‘short variants’ in RAS genes ( KRAS , NRAS , and HRAS) occurring at amino acid positions G12, G13, or Q61 that had a frequency 0.1% or greater were included. To estimate the number of new US cases of RAS -mutant PDAC, pancreatic cancer incidence estimates 3 were adjusted by the derived RAS mutational frequency values. All incidence estimates were rounded to the nearest 100. Results: Oncogenic RAS mutations were identified in 92% of PDAC patients, with nearly all being KRAS (91.8%) and the remaining NRAS (0.2%). No HRAS mutations passed our minimum frequency threshold requirement. Individual RAS mutations with frequency &gt;1% included KRAS G12D (39.9%), KRAS G12V (28.6%), KRAS G12R (14.6%), KRAS Q61H (4.2%), KRAS G12C (1.7%), and KRAS Q61R (1.4%). Applying these RAS mutation rates to reported PDAC incidence, we estimate that ~56,000 new patients with PDAC in USA per year will have tumors harboring an oncogenic RAS mutation, including ~51,000 of those with a RAS G12 mutation specifically. Conclusions: Oncogenic RAS mutations are identified from NGS testing in nearly all patients with advanced PDAC. Both the frequency and diversity of RAS mutations in PDAC suggest that PDAC is largely a RAS-driven cancer and that targeting RAS may be useful broadly in this disease. Mutational frequency and incidence at G12, G13, and Q61 amino acid positions in KRAS and NRAS among patients with PDAC. RAS G12 RAS G13 RAS Q61 RAS mutant Mutational Frequency KRAS 85.7% 0.8% 6.3% 91.8% NRAS 0.1% Below threshold 0.1% 0.2% Incidence KRAS 51,300 600 3,700 55,600 NRAS 100 Below threshold 100 200
Diverse stromal phenotypes at spatial resolution in colorectal cancer peritoneal metastasis.
Authors: Joseph J Zhao, Johnny Chin-Ann Ong, Ying Liu, Supriya Srivastava, Melissa Ching Ching Teo, Joey Jia-Ying Lee, Robert John Walsh, Lit-Hsin Loo, Qiu Xuan Tan, Gillian Ng, Joey Wee-Shan Tan, Haoran Ma, Xuewen Ong, Su Ting Tay, Taotao Sheng, Jeffrey H Y Lum, Wei-Peng Yong, Filippo Pietrantonio, Patrick Tan, Raghav Sundar
Journal: Journal of Clinical Oncology (2025)

218 Background: Peritoneal metastases (PM) in colorectal cancer (CRC) portend a poor prognosis. We sought to elucidate spatially resolved molecular features facilitating transcoelomic dissemination and progression. Methods: 50 PT, 116 PM and 37 primary normal samples from 96 patients were retrieved and profiled with digital spatial profiling (GeoMx DSP, Nanostring Technologies). Through unsupervised clustering, we characterized the microenvironment of tumor-stroma compartments and studied the roles of stromal phenotypes in promulgating tumorigenesis. These findings were orthogonally validated through spatial proteomics (multiplex IHC [mIHC] - COMET, Lunaphore Technologies) of 10 paired PT-PM samples retrieved from 6 patients. Results: A median of 37 region of interests (ROIs) (IQR: 32-38) were selected from a total of 9 tissue microarray (TMA) slides. A total of 269 ROIs (181 tumor, 88 stroma) from PM samples, 45 ROIs (34 tumor, 11 stroma) from PT samples and 28 (all stroma) ROIs from primary normal samples were retrieved and profiled. Through consensus clustering of stroma ROIs, we identify a fibro-collagenous and immune infiltrated stromal phenotype (stromal cluster [SC] 2) characterized by increased cancer associated fibroblasts (CAFs), memory B cells, M2 macrophages and T-cell exhaustion. Patients with SC2 stroma had poorer survival (p=0.036). SC2 stroma was also observed to support adjacent tumor compartments with enriched oncogenic pathways such as TGF-beta, TNF-alpha, hypoxia and JAK-STAT. Through discriminatory gene expression profiles, we developed a 20-gene composite bidirectional signature of SC2. The prognostic significance of the SC2-signature was externally validated through several cohorts including TCGA and MSI-H only cohorts. Next, by inspecting mIHC retrieved immune cell type densities across ROIs, we confirmed a similar phenomenon in which two distinct stromal clusters were found – one being fibroblast infiltrated but T-cell depleted (SC2-like, n=67 ROI) and another which is T-cell infiltrated but fibroblast depleted (SC1-like, n=104 ROI). Diverging spatial distributions of T-cells and fibroblasts between SC1 and SC2-like stroma was appreciated as well. Between both PT and PM, we find close clustering of T cells in SC1-like stromal compartments and fibroblasts in SC2-like stromal compartments. Conclusions: We describe SC2, a pro-tumorigenic stromal phenotype characterized by increased CAFs, T cell exhaustion and is associated with poor prognosis in CRC PM.
Long-term follow-up of the randomized trial on open versus laparoscopic surgery for primary tumor resection in patients with non-curable stage IV colon cancer (JCOG1107).
Authors: Akio Shiomi, Tomonori Akagi, Hiroyasu Kagawa, Riku Kajikawa, Hiroshi Katayama, Haruhiko Fukuda, Masaaki Ito, Jun Watanabe, Satoshi Ikeda, Masazumi Okajima, Shunsuke Tsukamoto, Atsuo Takashima, Yukihide Kanemitsu, Masafumi Inomata
Journal: Journal of Clinical Oncology (2025)

55 Background: The Japan Clinical Oncology Group (JCOG) 1107 (UMIN-CTR: UMIN000009715) was a non-inferiority phase III trial to compare laparoscopic surgery (LAP) with open surgery (OP) for symptomatic, non-curable stage IV colon cancer, using progression-free survival (PFS) as the primary endpoint based on the intention-to-treat principle. The planned primary analysis confirmed the non-inferiority of the LAP over the OP. Additionally, the present study aimed to compare the LAP and OP using long-term 3-year follow-up data from the JCOG1107. Methods: Eligibility criteria included pathologically proven adenocarcinoma or adenosquamous carcinoma; primary tumor located at the cecum, ascending, transverse, descending, sigmoid, and rectosigmoid colon; primary tumor with bowel stenosis and/or bleeding; and having at least one to three non-curable factors. The sample size was 194 with a power of 70%, one-sided alpha of 5%, and non-inferiority margin of the hazard ratio (HR) of 1.38. Results: In total, 195 patients were randomized (OP 95, LAP 100) between January 2013 and January 2021. OP was performed in 92 and LAP in 98 patients. Postoperative chemotherapy was administered in 82 OP and 86 LAP patients. As the data cut-off date of Feb 2024, 93 (98%) and 100 (100%) PFS event occurred in OP and LAP. The 3-year PFS were 5.3% (95% CI, 2.0-11.0) and 3.0% (0.8-7.8) for OP and LAP arms, respectively (HR: 1.028, 95% confidence interval [CI]: 0.772–1.370; P for non-inferiority = 0.0222). Regarding OS, 87 (92%) and 90 (90%) death occurred in OP and LAP. The 3-year OS were 31.5% (22.5-41.0) and 28.5% (20.0-37.6) for OP and LAP arms, respectively (HR: 1.048; 95% CI: 0.780–1.410). Conclusions: Long-term follow-up data supported the non-inferiority of LAP over OP for primary tumor resection in patients with non-curable stage IV colon cancer. Our study findings indicate that LAP is acceptable as a standard treatment for symptomatic, non-curable stage IV colon cancer. Clinical trial information: UMIN000009715 .
Tumour-free ctDNA detection as a decision tool to support organ preservation in node-negative rectal cancer undergoing neoadjuvant chemotherapy, excision, and observation in the phase II NEO trial (CCTG CO.28).
Authors: Jonathan M. Loree, Emma Titmuss, Carl J. Brown, Thereasa A. Rich, Dongsheng Tu, Derek J. Jonker, Christopher J. O'Callaghan, Hagen Fritz Kennecke
Journal: Journal of Clinical Oncology (2025)

20 Background: In the NEO trial (CCTG CO.28, NCT03259035) patients with node negative (N0) T1-T3 rectal cancer were treated with neoadjuvant CAPOX/FOLFOX and transanal excision surgery (TES) with the goal of organ preservation. Patients without documented response following neoadjuvant chemotherapy were recommended total mesorectal excision (TME). We present a post-hoc assessment of ctDNA detection in this early-stage population and correlate kinetics with response and outcomes. Methods: Fifty-eight patients enrolled in CO.28. Whole blood was collected in EDTA tubes and processed for future ctDNA analysis at up to six timepoints: pre-chemotherapy, after neoadjuvant chemotherapy (and pre-TES), yearly during surveillance for 3 years and upon progression. A total of 195 samples were analyzed with the Guardant Reveal™ assay: a tissue-free epigenomic assay leveraging &gt;20,000 epigenomic regions for ctDNA detection. Results: Of 48 available pre-treatment samples, ctDNA was detected in 22 (46%). Sensitivity by T-stage was 14% (1/7) for T1, 53% (17/32) for T2, 44% (4/9) for T3 cancers. ctDNA detection was lower following neoadjuvant chemotherapy (4/46, 9%, p&lt;0.001 vs pre-chemotherapy). Of 41 patients with paired pre- and post-chemo samples, 49% (20/41) had undetectable ctDNA at both timepoints, 44% (18/41) had reduced tumour fraction following chemotherapy, the majority of which completely cleared ctDNA (94%; 17/18) and 7% (3/41) had an increased tumour fraction following chemotherapy (67%, 2/3 changing from negative to positive), all three of whom failed to respond to neoadjuvant chemotherapy and had TME recommended (100%). In contrast, of those that cleared ctDNA following chemotherapy, 35% had TME recommended (6/17, p=0.074). Of five recurrences (3 distant, 2 local), all had negative or reduced ctDNA tumour fraction during neoadjuvant therapy before surgical intervention. Among patients with local relapse who were managed with TES, 1/2 (50%) had detectable ctDNA at the time of local progression. No samples were available for those with distant recurrences (3/5) at time of relapse. Conclusions: The Guardant Reveal tissue-free assay was able to detect ctDNA even in this extremely early-stage cohort and identified cancers with inadequate response to therapy and in whom TME was recommended. A tissue-free approach may support timeliness of ctDNA results that would support ctDNA as an additional decision tool with endoscopic and MRI assessments to increase physician and patient comfort with organ preservation. Clinical trial information: 03259035.
Impact of inpatient palliative care consultation on end-of-life care among patients with esophageal cancer.
Authors: Suriya Baskar, Robert Schoeneich, Chaula Desai, Udhayvir Singh Grewal
Journal: Journal of Clinical Oncology (2025)

502 Background: Esophageal cancer is an aggressive malignancy with a high global prevalence. Patients often suffer from various debilitating symptoms like dysphagia and cachexia, particularly with more advanced stage disease. Most patients continue to receive aggressive interventions until terminal stages of disease without timely initiation of formal palliative care (PC). We sought to investigate the impact of formal inpatient palliative care consultation on end-of-life (EOL) care among patients with esophageal cancer. Methods: The National Inpatient Sample (NIS) was queried to identify all hospitalizations with esophageal cancer utilizing ICD-10 codes C15.x from 2016 to 2020. Hospitalizations with documented inpatient mortality events were extracted and stratified based on reception of PC consultation (ICD-10 code Z51.5). Demographic and clinical data were analyzed using chi-squared tests and independent sample t-tests. A threshold of p-value less than 0.05 was set to determine statistical significance. Results: A total of 17,745 patients with esophageal cancer were included, of which 10,370 (58.4%) received PC consultation. Patients that received PC consultation at EOL were more likely to have higher comorbidities per CCI. No significant difference between age and sex was observed between the two cohorts. Patients who received PC consultations at EOL had higher rates of Do Not Resuscitate (DNR) code status (78.1% vs 43.2%, p &lt;0.001) and lower rates of aggressive interventions such as chemotherapy (0.9% vs 1.6%, p&lt;.001), blood transfusions (12.3% vs 18%, p&lt;.001), and mechanical ventilation (28.5% vs 41%, p&lt;0.001). No significant difference was observed in the rates of vasopressor use between the two groups (p=0.83). Hospitalizations with PC consultations were associated with significantly lower total hospitalization cost ($97,879 vs $146,128, p&lt;.001). Conclusions: Inpatient PC consultations among patients with esophageal cancer were associated with lower rates of aggressive interventions and higher rates of DNR code status in addition to significantly lower total hospitalization costs. These findings underscore the importance of inpatient PC consultation at the EOL in helping minimize aggressive interpretation and facilitate a greater focus on comfort and quality of life. No PalliativeN=7375 PalliativeN=10370 p-value Age (in years) 67.58 ± 10.9 67.58 ± 10.9 .98 CCI 9.1 ± 3.5 9.4 ± 3.3 &lt;.001 Mean length of stay (days) 8.9 ± 14.9 7.5 ± 11.3 &lt;.001 Total Charges 146128 ± 321830 97879 ± 195868 &lt;.001 DNR 3170 (43.2%) 8100 (78.1%) &lt;.001 Blood transfusion 1320 (18.0%) 1280 (12.3%) &lt;.001 Mechanical ventilation 3015 (41.0%) 2960 (28.5%) &lt;.001 Vasopressor 585 (8.0%) 835 (8.1%) 0.83 Chemotherapy 115 (1.6%) 95 (0.9%) &lt;.001