tbuckley/cabot-search huggingface dataset:
Personalized ctDNA monitoring to assess the recurrence of early stage pancreatic cancer after surgery.
Authors: Juan Du, Lu Zou, Hui-zi Sha, Fan Tong, Jiayao Ni, Jingjing Chen, Xinyuan Bai, Haochen Tang, Xiang Kong, Yaru Liu, Chengyi Wang, Meizhen Hu
Journal: Journal of Clinical Oncology (2025)

774 Background: Up to 80% of patients with resected pancreatic cancer recur within 2 years. Here, we assessed the feasibility and accuracy of a personalized, tumor-informed circulating tumor DNA (ctDNA) test for early warning of recurrence risk during long-term surveillance. Methods: This study retrospectively analyzed 43 patients who underwent radical surgery for pancreatic cancer between November 2021 and June 2023 at the Comprehensive Cancer Centre of Drum Tower Hospital, Clinical Cancer Institute of Nanjing University. A personalised panel was constructed to detect ctDNA in plasma based on whole-exon mutation information from tumour tissue. A total of 139 ctDNA samples were obtained from periods including postoperative, during adjuvant therapy, and post-treatment. Results: Until the last follow-up time (May 13, 2024), a personalised ctDNA monitoring panel was successfully constructed for 35 (81.4%) stage I-III patients with a median follow-up of 11.82 months (range: 2-17.8 months). A total of 16 patients experienced recurrence within 15.7 months (range: 5.4-30 months), with a median lead time from first positive ctDNA to imaging recurrence of 3.6 months (range: 1-9.3 months). ctDNA positivity was detected in 25.8% (8/31) of ctDNAs at the landmark time point (postoperative prior to adjuvant therapy), with a positive predictive value (PPV) of 75% (6/8) and a negative predictive value (NPV) of 69.6% (16/23). Patients with positive ctDNA at the landmark time point had inferior DFS (6.9 months vs undefined. HR 3.955, P=0.007) and OS (15 months vs undefined. HR 5.599, P=0.001) compared to those with negative ctDNA. When integrating longitudinal time points, PPV and NPV were 68.2% (15/22) and 91.7% (11/12), respectively. For all 16 relapsed patients, the sensitivity of positive ctDNA detected longitudinally was 93.75% (15/16). The ctDNA-MRD status at longitudinal time points had a more significant difference with DFS (undefined vs 12.6 months. HR 5.096, P=0.002) and OS (undefined vs 21 months. HR 6.487, P=0.038). Conclusions: Personalized ctDNA surveillance is effective in identifying high recurrence risk after pancreatic surgical resection. Long-term longitudinal warning of arbitrary ctDNA positivity suggests a recurrence probability of up to 93.75%; therefore, full ctDNA dynamic monitoring is essential. And ctDNA monitoring will be further used to guide the decision-making in the clinic to prolong patient survival.
Prognostic factors for gastric cancer patients with positive peritoneal cytology who underwent upfront surgery.
Authors: Takashi Abe, Masanori Terashima, Keiichi Fujiya, Taku Hattori, Kyota Takahashi, Yosuke Matsumoto, Yusuke Koseki, Kenichiro Furukawa, Yutaka Tanizawa, Etsuro Bando
Journal: Journal of Clinical Oncology (2025)

400 Background: Positive peritoneal cytology (CY1) is classified as Stage IV disease, the standard treatment for which is systemic chemotherapy. However, CY1 is often diagnosed after surgery in patients for whom staging laparoscopy is not indicated. In addition, the treatment strategy for patients with CY1 diagnosed during surgery is controversial. The Japanese guidelines recommend upfront surgery followed by adjuvant chemotherapy for patients diagnosed with CY1 during surgery. To identify patients with CY1 who are most likely to benefit from upfront surgery, we investigated prognostic factors in patients with CY1 who underwent upfront surgery. Methods: A total of 169 gastric cancer patients diagnosed as P0CY1 during or after surgery who underwent R1 resection other than positive resection margins were included. The diagnosis of CY1 was obtained by staging laparoscopy or during laparotomy in 69 patients and after surgery in 87 patients. Fourteen patients were initially diagnosed as CY0 by staging laparoscopy but were rediagnosed as CY1 after surgery. The clinicopathological factors of overall survival (OS) and progression-free survival (PFS) were investigated. Prognostic factors were identified using Cox regression models. Results: The median patient age was 72 years, and there were 108 males. The histological type was undifferentiated type in all of 102 patients. The macroscopic types were 0 in 10) patients 1 in 3, 2 in 27 3 in 84 and 4 in 45). cT grades and cN grades were cT1 in 3, cT2 in 7, cT3 in 12, cT4 in 147, cN0 in 65cN1 in 30), cN2 in 46 and cN3 in 28. The median OS and PFS were 25.1 months and 14.6 months, with 5-year OS rate and PFS rate of 30% and 23%, respectively. A multivariate analysis for OS identified macroscopic type 0-2, Charlson Comorbidity Index&lt;3, and adjuvant chemotherapy as independent prognostic factors. Similarly, macroscopic type 0-2, tumor size &lt;80 mm, and adjuvant chemotherapy were identified as independent prognostic factors for PFS. In a subgroup analysis of patients who received adjuvant chemotherapy, macroscopic type 0-2 was the only independent prognostic factor for PFS. The 5-year PFS rate in patients with macroscopic type 0-2 was 42%. Conclusions: Patients with macroscopic type 0-2 who are suitable for adjuvant chemotherapy may have benefit from upfront surgery, even if peritoneal cytology is positive.
Prognostic factors for thermo-ablation of liver metastases in colon cancer: A Maltese perspective.
Authors: Malcolm Buhagiar, Angeline Sapiano, Amanda Darmanin, David Karl Caruana, Kelvin Cortis, Christine Cannataci
Journal: Journal of Clinical Oncology (2025)

267 Background: Malta is a small Mediterranean archipelago with an annual colon cancer incidence of 300 patients per year and a cumulative 5-year overall survival of 58%. Despite major improvements in therapeutic strategies, colon cancer remains the third leading cause of cancer deaths locally with an annual mortality rate of circa 110 patients per year. Percutaneous thermal ablation of colorectal liver metastases involves exposure of metastatic deposits to temperature extremes using radiofrequency, microwave or cryotherapy. The role of this case series was to examine the prognostic value of clinico-pathological variables to provide insight into patient selection for ablative therapy. Methods: This retrospective analysis of 66 adult patients with colorectal liver oligometastatic disease who underwent thermal ablation between January 2014 and January 2022, reviews demographic and pathological criteria including tumour grade, presence of vascular invasion, mismatch repair and k-RAS &amp; BRAF mutational status, CEA &amp; Ca19.9 assay at time of treatment. Other parameters include metachronous versus synchronous disease, hepatic burden and concurrent chemotherapy. All these co-variables were analysed using the Cox Regression Hazard model to assess their impact on progression free- (PFS) and overall survival (OS). Results: For this patient cohort, the mean PFS and OS were 13.1 and 33.8 months. Our data indicates that most individuals experience progression within the first 10 months, with a gradual decline in PFS for the remaining individuals. A Ca19.9 level within normal limits (p=0.004, HR 0.157-0.700 95% CI) was related to an improved PFS but not OS. The presence of synchronous metastases (p=0.004, HR 0.168-0.715 95% CI) and ablation of one lesion (p=0.013 HR 0.191 (0.052-0.702 95 CI) were favourable prognostic markers for improved OS. k-RAS wt status was a prognostic adverse biomarker for PFS (p=0.002, HR 1.529, 6.686 95% CI). There was a paucity of data for BRAF and MMR status so these were excluded from the final analysis. No statistical survival benefit was noted for patients treated with chemotherapy, and other variables including gender, age, primary tumour sidedness, LVSI or CEA value. Conclusions: There are two surprising trends here- the paucity of survival benefit for the use of chemotherapy in conjunction with ablation and the worse outcome for k-ras wt tumours. We postulate that the absence of BRAF sub-stratification at the time of patient accrual, impacted statistical hazard. This case series suggests that the prognosis and survival of colorectal liver oligometastatic disease is multifactorial and complex, highlighting the need for further genomic and molecular insights.
Impact of synchronous vs metachronous primary tumor resection on prognosis of BRAF-V600E mutant metastatic colorectal cancer (mCRC).
Authors: Arwa Isameldin Ahmed, William Philips, Horia Marginean, Timothy R. Asmis, Michael M. Vickers, Bryan Lo, Rachel Anne Goodwin
Journal: Journal of Clinical Oncology (2025)

304 Background: The goal of this study is to evaluate if resection of the primary tumor in synchronous versus metachronous metastatic disease predicts survival of BRAF-V600E mCRC in the era prior to combination BRAF/EGFR inhibitors. Methods: This is a retrospective study of patients treated at the Ottawa Hospital Cancer Centre with BRAF-V600E mutation mCRC who did not receive combination BRAF/anti-EGFR therapy, diagnosed with colorectal cancer prior to March 31, 2021. Demographic, clinical, pathologic and cancer characteristics were abstracted from electronic medical records. Outcomes of interest included median duration of therapy and overall survival (OS). Results: 71 patients were included with a median age of 70 years:, 37 (52%) were females, 49 (69%)had right-sided tumors and 19 (27%) were mismatch repair deficient (dMMR). The primary tumor was unresected in 22 (30%) and resected in 49 (70%), completely resected in 44 (62%), and partially resected in 5 (7%) patients. Overall, median OS was 12.9 months 95% CI (8.4, 19) with 17 months 95% CI (11, —) mOS in patients with resected primary and 6.3 95% CI (4.8, 15) months in patients with unresected primary, HR 2.48 95% CI (1.42, 4.32), p=0.001. In univariate analysis: signet ring cell (p=0.007), good performance status (p&lt;0.001), distant lymph nodes (p&lt;0.001), peritoneal metastasis (p=0.008), metasetectomy (p=0.002), Charlston Comorbidity Index (p=0.003) were significant prognostic factors. Synchronous versus metachronous primary tumour was not a significant prognostic factor. Conclusions: Real world data confirms that patients with BRAF-V600E mutant mCRC have poor clinical outcomes. Our analysis suggests that resection of the primary tumor did not seem to impact on survival of BRAF-V600E mutant mCRC patients. This suggests that prognosis is dictated by the systemic disease and not complications of the primary tumour itself. Of the patients with unresected primary tumour (n=21), 6 were synchronous. Metastatic status Primary Tumor Resected Primary Tumor unresected Total Synchronous 23 22 45 Metachronous 26 0 26 Total 49 22 71
Systematic literature review (SLR) of prognostic factors (PFs) in locally advanced rectal cancer (LARC) and mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer (RC).
Authors: Jaume Capdevila, Sean O’Donnell, Katarzyna Borkowska, James Frampton, Marissa Betts, Courtney Maierhofer, Linda Kalilani, Jamie Garside, Huifen Wang
Journal: Journal of Clinical Oncology (2025)

303 Background: Innovative immunotherapies arebeing developed to improve clinical outcomes in patients (pts) withdMMR/MSI-H LARC who respond poorly to the current standard of care. A comprehensive overview of PFs in dMMR/MSI-H LARC may provide insight into the natural history of this disease to inform clinical study design and pt risk stratification. Methods: Systematic searches of bibliographic databases (EMBASE, MEDLINE, Cochrane; 2013–2023) and congress websites (2021–2023) were conducted to identify PFs for tumor response and survival outcomes in adult pts with LARC (SLR1) and dMMR/MSI-H RC (SLR2). Given the expected high volume of evidence, SLR1 was limited to large observational studies (≥1000 pts) and clinical trials (≥100 pts); SLR2 had no such limits. Results: 95 of 2307 publications met the inclusion criteria for SLR1. Of the PFs reported in ≥20 studies, older age, more lymph node involvement or fewer nodes assessed, higher T-stage or larger tumor size, higher histologic grade, and more comorbidities were most frequently significantly associated with poorer patient prognosis (Table). 3 of 289 publications met the inclusion criteria for SLR2. Neoadjuvant chemoradiation therapy (CRT) compared to chemotherapy (CT) was associated with statistically significant worse disease-free survival (DFS) and distant metastasis-free survival (DMFS), while T- or N-stage, age, and sex did not significantly impact these outcomes. Low vs middle tumor localization was also associated with worse DMFS. Stage III and IV disease were associated with worse RC-specific survival, while surgical procedure (segmental vs extended) showed no difference in overall survival (OS). The addition of neoadjuvant CRT or adjuvant CRT/CT to surgery alone had no impact on OS but was associated with worse DFS. Conclusions: Evidence regarding PFs in dMMR/MSI-H RC is scarce and may limit its interpretability, highlighting the need for further research that may be informed by the PFs identified from SLR1. The results from these SLRs may be helpful for optimizing patient management and treatment decision making, and to further contextualize RC clinical trials. PFs reported in ≥20 studies with ≥75% of studies reporting significant results in pts with LARC. PF Studies reporting PF (n) Studies reporting significant* impact of PF on prognosis (%) Poorer prognosis group Top 2 most frequently reported outcomes Age 59 81.4 Older OS, DFS Lymph node involvement/assessment 55 78.2 Yes or higher N stage OS, DFS T-stage or tumor size 53 79.2 Higher or larger OS, DFS Histologic grade 37 75.7 Higher OS, pathological complete response (pCR) Comorbidities 23 87.0 More OS, pCR *p-value &lt;0.05 was considered significant as reported in the identified studies.
Safety and efficacy of perioperative chemotherapy combined with PD-1 inhibitor versus chemotherapy with D2 gastrectomy plus PAND in gastric cancer with PALD metastasis: A single-center retrospective cohort study.
Authors: Yian Du, Zeyao Ye
Journal: Journal of Clinical Oncology (2025)

368 Background: Gastric cancer with para-aortic lymph node (PALD) metastasis is associated with a poor prognosis. When the metastasis is limited to the PALD, preoperative systemic therapy combined with D2 gastrectomy plus para-aortic lymph node dissection (PAND) may enhance survival. The benefit of perioperative chemotherapy combined with immune checkpoint inhibitors for these patients is unknown. Methods: A total of 133 patients with gastric cancer and limited No.16a2/b1 lymph node metastasis underwent perioperative systemic therapy combined with D2 gastrectomy plus PAND. Patients receiving chemotherapy combined with a PD-1 inhibitor were assigned to Group A (n=62), while those receiving chemotherapy alone were assigned to Group B (n=71). Pathological response, safety, efficacy, and survival outcomes were compared between the two groups. Results: Adverse events occurred at comparable rates between the two groups. No treatment-related deaths occurred in either group. In Group A, all patients (100%) achieved R0 resection, compared to 70 patients (98.6%) in Group B. Group A showed significantly better pathological outcomes than Group B, with higher rates of pathological complete response (pCR) (37.1% vs. 4.2%, P &lt; 0.001), and major pathological response (MPR) (58.1% vs. 22.5%, P &lt; 0.001). Group A showed a higher 2-year overall survival (OS) rate compared to Group B (90.3% vs. 62.9%, P = 0.011). The median overall survival (mOS) in Group B was 35.0 months, while follow-up data for Group A are currently insufficient to assess mOS. Conclusions: The addition of a PD-1 inhibitor to chemotherapy significantly improves the pathological response rate and prognosis in gastric cancer patients with PALD. Notably, the combination did not increase adverse events. These findings suggest that combining PD-1 inhibitor with chemotherapy could be a promising strategy for improving outcomes in this patient population, though further prospective studies are necessary to confirm long-term survival benefits. Postoperative outcomes and pathological response. Variable Group A (n=62) % Group A (n=71) % P Value Vascular tumor embolus 0.005 Negative 43 69.4% 32 45.1% Positive 19 30.6% 39 54.9% Nerve infiltration 0.004 Negative 44 71.0% 33 46.5% Positive 18 29.0% 38 53.5% No.16a2/b1 0.057 Negative 53 85.5% 51 71.8% Positive 9 14.5% 20 28.2% Tumor resection 0.970 Distal 26 41.9% 30 42.3% Total 36 58.1% 41 57.7% Serum CEA (U/mL） 0.805 Normal 56 90.3% 65 91.5% &gt;5 6 9.7% 6 8.5% Serum CA125 (U/mL) 0.280 Normal 30 48.4% 41 57.7% &gt;35 32 51.6% 30 42.3% Serum CA199 (U/mL) 0.783 Normal 56 90.3% 65 91.5% &gt;37 6 9.7% 6 8.5% pT-stage &lt;0.001 ≤T2 37 59.7% 19 26.8% ＞T2 25 40.3% 52 73.2% pN-stage 0.001 N0/1 42 67.7% 27 38.0% N2/3 20 32.3% 44 62.0% TRG ＜0.001 0 23 37.1% 3 4.2% 1 13 21.0% 13 18.3% 2 22 35.5% 47 66.2% 3 4 6.5% 8 11.3% pCR 23 37.1% 3 4.2% ＜0.001 MPR 36 58.1% 16 22.5% ＜0.001
Overall survival (OS) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line (1L) FOLFIRINOX (FFX): Bridging the gap between the NAPOLI 3 trial and real-world practice.
Authors: Paul Cockrum, Rose Chang, Louise Huafeng Yu, Chunyi Xu, Mei Sheng Duh, George P. Kim
Journal: Journal of Clinical Oncology (2025)

690 Background: NALIRIFOX (liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin) demonstrated significantly improved OS compared to 1L gemcitabine + nab-paclitaxel in the phase 3 NAPOLI 3 trial (NCT04083235). The median OS (95% CI) in the NALIRIFOX intention-to-treat population (N= 383) was 11.1 (10.0, 12.1) months. However, the relative efficacy of NALIRIFOX versus FFX (irinotecan + 5-fluorouracil/leucovorin + oxaliplatin), another standard of care for 1L treatment of mPDAC, has not been studied. To further contextualize findings from NAPOLI 3 trial, the current study described OS among patients treated with 1L FFX in the real-world setting. Methods: Three cohorts of patients with mPDAC treated with 1L FFX were identified from the Flatiron Health database. The all-comer cohort included all adult patients with mPDAC treated with 1L FFX since January 2014. Among them, the trial-aligned cohort included patients with mPDAC treated with 1L FFX between January 1, 2020 and July 31, 2022 (to align with the time period of NAPOLI 3 trial) who met the eligibility criteria of NAPOLI 3. Finally, a subgroup of patients in the trial-aligned cohort who received modified FFX (mFFX) regimen composed the trial-aligned mFFX cohort. OS was assessed using Kaplan-Meier analysis. Results: The all-comer cohort consisted of 3,271 patients. The trial-aligned cohort included 219 patients, of whom 154 (70%) were treated with mFFX. The distribution of baseline characteristics was similar across three cohorts (Table). The median age of the trial-aligned cohort was 65 years old, with 46% of patients being female, 67% being White, and 47% having ECOG score of 1. The median OS (95% CI) in the all-comer cohort and trial-aligned cohort was 9.0 (8.5, 9.3) months and 9.1 (7.8, 10.9) months, respectively; the median OS (95% CI) was 8.6 (7.3, 10.5) months in the trial-aligned mFFX cohort. Conclusions: NALIRIFOX regimen in the NAPOLI 3 trial showed numerically improved OS compared to FFX, including mFFX, in the real-world setting. Analysis adjusting for baseline characteristics are warranted and will provide further insights for the comparative efficacy of the two regimens. Characteristics of real-world FOLFIRINOX cohorts. All-comer cohort(N=3,271) Trial-aligned cohort(N=219) Trial-aligned mFFX cohort (N=154) Baseline characteristics Age, years, mean (SD) 63.5 (9.0) 64.6 (8.2) 65.1 (8.5) Female, n (%) 1,377 (42.1) 100 (45.7) 68 (44.2) White, n (%) 2,118 (64.8) 146 (66.7) 100 (64.9) ECOG score = 1, n (%) 1,327 (48.9)* 103 (47.0) 77 (50.0) Endpoint Median OS, months (95% CI) 9.0 (8.5, 9.3) 9.1 (7.8, 10.9) 8.6 (7.3, 10.5) Abbreviations: CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; OS, overall survival; SD, standard deviation. *Proportion calculated based on 2,711 patients with ECOG available at baseline.
Landscape of novel gene fusions in gastrointestinal tumors.
Authors: Aysegul Balyimez, Karen L White, Jess R Hoag, Arthur Starodynov, Fadel S. Alyaqoub, Pawan Noel, Shoudong Li, Gargi D. Basu, Jean-Paul De La O, Ariane C. Kemkes
Journal: Journal of Clinical Oncology (2025)

268 Background: Gene fusions are recognized as critical drivers of cancer and targets for precision therapies. The 2022 ASCO provisional clinical opinion on tumor genomic testing includes recommendations for fusion testing and recognizes the strengths of RNA-based approaches. Targeted DNA/RNA sequencing panels can be used to detect well characterized, clinically actionable fusions, but their ability to detect rare novel fusions (i.e., those with uncharacterized fusion partners) can be limited by assay design. Whole-exome, whole-transcriptome sequencing (WES/WTS) may improve the identification of actionable gene fusions by detecting both known and novel fusions. This work describes clinically actionable novel fusions detected in gastrointestinal (GI) cancers. Methods: The study included samples from GI cancers that were analyzed using the OncoExTra test between May 2018 and May 2024. The assay uses tumor-normal WES/WTS to identify somatic alterations, including gene fusions with known and unknown partners and breakpoints.Clinical data were queried foractionable fusions with novel fusion partners that were unique in the entire laboratory database and have not, to our knowledge, been previously reported in the existing scientific literature or public databases. Actionable fusions were defined as those associated with FDA-approved targeted therapies or those that made patients eligible for a clinical trial. Results: Tumor samples from 2,776 patients with GI cancers were evaluated with a total of 75 actionable fusions identified in samples from 74 patients. Of these, 25.3% (n=19) were novel, and 74.7% (n=56) were previously described or recurrent fusions. Novel fusions were detected in small bowel (2 of 81), colorectal (4 of 1,621), gastric/gastroesophageal junction (GEJ) (2 of 259), pancreatic (7 of 466) and biliary (4 of 131) cancers. Thirteen (63.2%) of the novel fusions involved genes associated with FDA-approved therapies, including FGFR2 (n=6), BRAF (n=3), MET (n=2), FGFR1 (n=1) and NTRK2 (n=1). Of the fusions associated with FDA-approved therapies, 20% (8/40) of recurrent fusions and 38.5% (5/13) of novel fusions were detected only by RNA sequencing. No fusions were identified in appendiceal or esophageal cancers. Conclusions: Gene fusions with novel fusion partners represented one fourth of all actionable fusions detected in GI tumors. Use of a comprehensive WES/WTS testing approach that detects fusions agnostic of the fusion partner may affect clinical care in GI cancers by increasing the number of patients eligible for targeted therapies.