tbuckley/cabot-search huggingface dataset:
Chemotherapy selection for advanced or metastatic pancreatic cancer using machine learning models trained with multi-center datasets.
Authors: Moonho Kim, Gyucheol Choi, Jaekyung Cheon, Changhoon Yoo, Jamin Koo
Journal: Journal of Clinical Oncology (2025)

738 Background: Several factors must be considered when selecting the chemotherapeutic regimen for advanced or metastatic pancreatic cancer. The decision between FOLFIRINOX and Gemcitabine/Nab-paclitaxel (GnP) as the first-line therapy is challenging, as survival is influenced by the efficacy and toxicity profiles of these treatments, along with individual patient characteristics and therapeutic vulnerabilities. This study aims to facilitate the selection of an appropriate first-line regimen for advanced or metastatic pancreatic cancer by employing machine learning (ML) methods trained on multi-center datasets. Methods: Our study is based on a cohort of 191 patients who underwent systemic chemotherapy for advanced or metastatic pancreatic cancer at the Gangneung Asan Hospital and Asan Medical Center in South Korea between 2014 and 2023. The dataset consisted of 17 types of demographic and clinical characteristics, as well as time-course of response and survival outcomes. We divided the cohort into training and test groups (4:1) in a stratified manner. ML models predicting overall survival (OS) were trained on the former group using the CatBoost method. The models utilizing a minimal subset of variables were selected with respect to ROC-AUC during 5-fold cross validation. A patient was classified as having high risk to a therapy when the predicted probability of death following treatment initiation was above the threshold value as determined during training of the respective model. Results: The median age of the entire cohort was 62 years, with 64% being male. The ML models achieved ROC-AUCs of 0.81 and 0.82 when predicting early death within 12 months following the initial administration of FOLFIRINOX or GnP, respectively. The predictive accuracies of the models were 0.77 and 0.80 for the unseen datasets from the two treatment groups, respectively. The median OS of the high- versus low-risk groups of FOLFIRINOX predicted by the ML models were significantly different (9 vs 15 months, P &lt;0.0001), with a hazard ratio (HR) of 2.8. Similarly, the median OS of the high- and low-risk groups of GnP were significantly different (9 vs 18 months, P &lt;0.01, HR of 2.5). We observed that 27% of the patients predicted as high risk to FOLFIRINOX therapy were predicted as low risk to GnP and vice versa for 32% of the patients predicted as high risk to GnP therapy. Conclusions: We developed ML models to compute the probability of early death following FOLFIRINOX or GnP therapy from routinely collected data of the patients with advanced or metastatic pancreatic cancer. After confirming robust predictive performance with multi-center datasets, we believe that these models may assist clinicians in selecting a first-line regimens, potentially enhancing personalized treatment strategies for this challenging disease.
Differences in disease characteristics in young vs older adults with colorectal carcinoma.
Authors: Shivani Modi, Supriya Peshin, Nagaishwarya Moka, Gahyun Gim, Adit Dharia
Journal: Journal of Clinical Oncology (2025)

34 Background: Colorectal carcinoma (CRC) exhibits distinct disease characteristics between younger (≤50 years) and older (&gt;50 years) adults, which may significantly influence treatment decisions and outcomes. This study aims to investigate differences in disease characteristics of colorectal carcinoma among patients aged ≤50 years compared to those aged &gt;50 years, utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: A retrospective analysis was performed using the SEER database covering the years 2000 to 2020. A total of 150,000 diagnosed CRC cases were included. Key variables analyzed comprised stage at diagnosis, tumor grade, histological subtype, and 5-year survival rates. Rates of CRC diagnoses in various age brackets were calculated for three time periods: 2000-2010, 2010-2020, and overall from 2000-2020. Results: Within the total cohort, 12% (18,000 cases) were diagnosed in young adults, while 88% (132,000 cases) were in older adults. An analysis of age-specific rates showed: 2000-2010 : Young adults (≤50 years) represented 10% of CRC cases, with 16% presenting at advanced stages (Stage III or IV). 2010-2020 : This group increased to 12%, with 65% diagnosed at advanced stages (Stage III or IV), compared to 52% in older adults (p &lt; 0.001). In terms of tumor characteristics, poorly differentiated tumors were more prevalent in young adults (28% vs. 18%, p &lt; 0.001). The prevalence of microsatellite instability-high (MSI-H) tumors was significantly greater in young adults at 18%, compared to 12% in older adults (p &lt; 0.05). The 5-year overall survival rate for young adults was 68%, notably higher than the 48% for older adults (p &lt; 0.001). Conclusions: This study underscores significant differences in disease characteristics between young and older adults with colorectal carcinoma. Young patients are more likely to present with advanced disease but have better survival outcomes. These findings indicate the necessity for an age specific approach to screening and treatment strategies. Differences in stage at diagnosis, tumor grade, presence of MSI-H, and survival outcomes between younger and older adults diagnosed with colorectal carcinoma. Category Young Adults (≤50 years) Older Adults (&gt;50 years) p-value Proportion of Total CRC Cases 12% (18,000 cases) 88% (132,000 cases) Advanced Stage (Stage III or IV) 65% (2010-2020) 52% (2010-2020) &lt; 0.001 Poorly Differentiated Tumors 28% 18% &lt; 0.001 Microsatellite Instability-High (MSI-H) 18% 12% &lt; 0.05 5-Year Overall Survival Rate 68% 48% &lt; 0.001
MEK inhibitor-based therapy in metastatic pancreatic adenocarcinoma with <i>KRAS</i> G12D or <i>KRAS</i> G12V alteration.
Authors: Stephanie Yohay, Grace Ying, Elizabeth Auckley, Mohammed Aldakkak, Samih Z Thalji, Parnian Vakili, Justin Grahl, Bradley Mayer, Faisal Shahjehan, Soon Khai Low, Douglas B. Evans, Kathleen K. Christians, Yongwoo David Seo, Beth Erickson, William Adrian Hall, Thomas McFall, Razelle Kurzrock, Ben George, Mandana Kamgar
Journal: Journal of Clinical Oncology (2025)

726 Background: Up to 95% of pancreatic ductal adenocarcinomas (PDAC) are driven by oncogenic alterations in the KRAS gene, with KRAS G12D (40%) and KRAS G12V (30%) mutations being the most common. However, in most cases, KRAS alterations are accompanied by alterations in other tumor suppressors such as TP53 , CDKN2A/B , and SMAD4 . Therefore, targeting KRAS alone may not be sufficient for effective treatment of PDAC . As part of the MCW-Master-PREDICT (NCT05802069) observational study, we evaluated the effectiveness of MEK inhibitor (MEK-inh)-based therapy, tailored to the unique molecular alterations of each patient’s tumor, in treating metastatic PDAC (mPDAC) with KRAS G12D or KRAS G12V alterations. Methods: From April 2022 to December 2023, 19 patients ( KRAS G12D=10 (53%), KRAS G12V=9 (47%)) were treated with MEK-inh-based therapy. Comprehensive genomic profiling was performed using Tempus xT (648 genes) in 15 patients (79%), FoundationOne (324 genes) in 4 patients (21%), and STRATA (429 genes) in 1 patient. The genomic characteristics, matched therapies, and treatment outcomes are provided (Table). Results: Of the 19 patients, 11 (58%) were female. The median age at the initiation of MEK-inh-based therapy was 67 years. Six (32%) patients received MEK-inh-based therapy as first or second-line treatment, while 13 (68%) patients were treated in the third to fifth-line. Among the 19 patients, the median overall survival (mOS) and median progression-free survival (mPFS) from the initiation of MEK-inh-based therapy were 5 and 2 months, respectively. The mOS from the time of MEK-inh-based therapy was 5.1 months for KRAS G12D, and 4.7 months for KRAS G12V (P=0.87). The mPFS from the time of MEK-inh-based therapy was 2.3 months for KRAS G12D and 1.4 months for KRAS G12V (P=0.12). Among all 19 patients, 4 (21%) patients had mPFS above 4 months ( KRAS G12V=1, KRAS G12D=3; 4.1, 4.3, 4.7, 9.9 months). Conclusions: The efficacy of MEK-inh-based therapy was limited in the late-line treatment of mPDAC for patients with KRAS G12D and KRAS G12V mutations. The potential role of MEK inhibitors in earlier lines of therapy, and their combination with KRAS inhibitors, requires further prospective evaluation. Tumor alterations and matched therapies. Altered gene KRAS G12V(N=9) KRAS G12D(N=10) Patients matched(N=19) Type of matched therapy KRAS G12D/V 9 (100%) 10 (100%) 19 (100%) MEK inhibitor TP53 7 (78%) 8 (80%) 8 (42%) VEGF/VEGR inhibitor* CDKN2A/B 8 (89%) 5 (50%) 9 (47%) CDK4/6 inhibitor** SMAD4 3 (33%) 4 (40%) 4 (21%) MEK inhibitor + (EGFR or pan-HER inhibitor) *** *PMID: 27466356; **PMID: 33472910; ***PMID: 36127339, PMID: 24625091. N= number of patients.
The influence of depression on esophageal cancer outcomes: Using the National Inpatient Sample (NIS) 2021.
Authors: Kalaivani Babu, Srinishant Rajarajan, Charmi Bhanushali, Sruthi Ramanan, Asmi Chattaraj, Sai Prasad Ramachandran, Nithya Ramesh, Himshikar Khataniar, Amit Correa
Journal: Journal of Clinical Oncology (2025)

338 Background: Esophageal cancer (EC) remains a challenging malignancy with high morbidity and mortality rates. Depression is prevalent among cancer patients and has been shown to affect various clinical outcomes. This study aims to evaluate the impact of depression on mortality, length of stay (LOS), and hospitalization charges in patients with esophageal cancer using data from the NIS. Methods: We conducted a retrospective, population-based study using the NIS data to analyze patients diagnosed with esophageal cancer. Depression was the primary exposure variable using the appropriate ICD-10 code. We applied survey-weighted descriptive statistics, logistic regression, and linear regression models to assess outcomes, adjusting for demographic and clinical factors, including age, sex, race, comorbidities (Charlson Comorbidity Index), hospital teaching status, and regional characteristics. Results: A total of 40,855 patients with esophageal cancer were included, with 11.4% (n = 4,855) having a concurrent diagnosis of depression. The unadjusted mortality rate for the cohort was 9.18%, with depressed patients showing a lower mortality rate (6.45% vs. 9.53%, p = 0.0018). After adjusting for covariates, depression was associated with significantly lower in-hospital mortality (adjusted OR 0.63, 95% CI 0.48–0.83, p = 0.001). While the unadjusted mean length of stay (LOS) was slightly higher in depressed patients (7.66 vs. 7.25 days, p = 0.132), adjusted models showed no significant difference (β = 0.42 days, p = 0.132). Depression was associated with lower unadjusted total hospitalization charges ($92,321 vs. $104,156, p = 0.023), and in adjusted analyses, depressed patients incurred significantly lower costs (β = -$10,327, 95% CI -$19,233 to -$1,421, p = 0.023). Significant predictors of increased hospitalization charges included teaching hospital status (β = $34,029, p &lt; 0.0001) and large hospital size (β = $38,481, p &lt; 0.0001). Conclusions: Depression, while common among patients with esophageal cancer, was unexpectedly associated with lower in-hospital mortality, despite a longer length of stay and higher comorbidity burden. This suggests that depressed patients may receive more comprehensive or prolonged care, which could contribute to their reduced mortality risk. Additionally, despite extended hospital stays, these patients incurred significantly lower hospitalization costs, indicating possible differences in resource utilization or treatment intensity. These findings highlight the complex relationship between mental health and cancer outcomes, emphasizing the need for further research to explore the mechanisms behind these associations and to better tailor care for esophageal cancer patients with depression.
Clinical outcomes of adjuvant chemoradiotherapy in pancreatic adenocarcinoma with R1 resection.
Authors: Wahyu Wulaningsih, Amy Ah-Moye, Asadullah Khan, Nishanthi Senthivel, Diana M. Tait, Irene Yu-Shing Chong, Brian Hin, Monica Terlizzo, Ricky Harminder Bhogal, Kai Tai Derek Yeung, Katharine Aitken
Journal: Journal of Clinical Oncology (2025)

731 Background: The benefit of chemoradiotherapy (CRT) following adjuvant chemotherapy in pancreatic cancer is unclear, though recent findings suggest some disease-free survival benefit over chemotherapy alone. We aimed to assess overall (OS) and progression-free survival (PFS) and patterns of disease recurrence following adjuvant chemoradiotherapy (CRT) in pancreatic adenocarcinoma patients with R1 resection (defined as &lt;1mm). Methods: We retrospectively collected data of patients with pancreatic adenocarcinoma who underwent adjuvant CRT (50.4-54Gy) following surgery with R1 resection between 2007-2023 in a single centre in the UK. Clinical data was collected from electronic medical records and information on radiotherapy was collected from treatment planning systems (TPS). Toxicity during and after CRT was graded with Common Terminology Criteria for Adverse Events (CTCAE). OS and PFS were measured with Kaplan-Meier curves from the time of surgery to death or disease progression or last follow up. In-field and locoregional recurrence were determined from restaging scans compared against radiotherapy field in TPS. Results: Among 33 patients included, 27 (81.8%) died within median follow-up 39 (14.8-111.4) months. All patients received adjuvant chemotherapy prior to CRT. Median OS was 42 (21.6-52.7) months and median PFS was 18.2 (15.5-28.4) months. In all but one patient, the R1 involved the posterior resection margin. Most patients (84.8%) had documented disease progression. In the majority the site of first progression was distant metastatic disease (51.5%), whilst six (18.2%) had local recurrence within the radiotherapy field. Four (12.1%) relapsed locoregionally. No statistically significance difference in OS or PFS was seen with presence of perineural or lymphovascular invasion, though analysis was limited by low number of patients. The majority of patients (72%) were node positive on pathology. Two (6.1%) patients had grade 3-4 toxicity during CRT (neutropenic and non-neutropenic sepsis). Conclusions: Our study supported acceptable safety following CRT as an adjuvant treatment in pancreatic cancer patients with R1 resection on surgery. Despite R1 resection, we observed survival outcomes with adjuvant chemotherapy and CRT somewhat above previously reported data. However the benefit of CRT after adjuvant chemotherapy remains unclear. Further evaluation is warranted to clarify which subgroups of patients benefit.
Commentary to the Editor from Manucha et al.: Blood Pressure Decreases in Overweight Elderly Individuals on Vitamin D: A Randomized Trial
Authors: José Luis Mansur
Journal: Clinical Cardiology and Cardiovascular Interventions (2024)

The excellent manuscript by Rahme M et al., post hoc exploratory analyses of 221 ambulatory older overweight individuals supplemented with calcium and oral vitamin D3, shed light on an existing problem. We mean Vitamin D is associated with hypertension, but its supplementation did not produce positive results.
Rechallenge with epidermal growth factor receptor inhibitors for metastatic colorectal cancer: A systematic review and meta-analysis.
Authors: Amy H. Huang, Ronan Wenhan Hsieh, Chuan Lu, Ibrahim Halil Sahin, Gentry Teng King, Rachael A. Safyan, Stacey A. Cohen, David Bing Zhen, Veena Shankaran, William P Harris, Andrew L. Coveler, Po-Jen Lin, Jyoti Malhotra, Victoria Forbes, E. Gabriela Chiorean, Gin Yi Lee
Journal: Journal of Clinical Oncology (2025)

184 Background: Clonal evolution is a mechanism of treatment resistance against epidermal growth factor receptor inhibitors (EGFRi) in metastatic colorectal cancer (mCRC). Upon EGFRi discontinuation, EGFRi-resistant subclones decay with time, which allows for EGFRi rechallenge. We conducted a meta-analysis to investigate the efficacy of EGFRi rechallenge for patients with mCRC. Methods: Clinical trials and cohort studies investigating the efficacy of EGFRi rechallenge were extracted from PubMed and Embase from inception to January 31, 2024. Hazard ratios (HR) of overall survival (OS) and progression-free survival (PFS) were aggregated using random-effects models. Results: Among 179 studies initially retrieved from the databases, 23 studies (665 patients) were included in the final analysis. There were 11 single-arm trials, 5 randomized controlled trials (including 3 post-hoc analyses), and 7 observational studies. At least 444 patients (66.8%) had left-sided mCRC. In 19 studies, EGFRi rechallenge was given only for patients previously progressing on 5-fluoropyrimadine, oxaliplatin and irinotecan. RAS/RAF mutation status was assessed with circulating tumor DNA (ctDNA) or tissue-based sequencing right before EGFRi rechallenge in 13 studies. Ten clinical trials only enrolled patients with RAS/RAF-wild type mCRC for EGFRi rechallenge. The median EGFRi-free interval before EGFRi rechallenge was ≧4 months in 13 studies (≥10 months in 9 studies) and between 2 to 4 months in 3 studies. Thirteen studies reported an objective response rate (ORR) up to 70%. Eight out of the 13 studies (61.5%) reported an ORR &gt;10% (7 studies with ORR &gt;20%), which is numerically higher than that achieved by FDA-approved third-line agents for mCRC (ORR &lt;10%). EGFRi rechallenge was associated with significantly longer pooled OS (HR 0.62; 95%CI, 0.42-0.92; I 2 =51.9%) and pooled PFS (HR 0.55; 95%CI, 0.38-0.79; I 2 =5.5%) than non-EGFRi systemic therapy. Patients without detectable RAS/RAF mutations by ctDNA right before EGFRi rechallenge had a significantly longer OS (HR, 0.39; 95%CI, 0.23-0.66; I2=32%) and PFS (HR, 0.41; 95%CI, 0.29-0.59; I2=0%) than those with detectable RAS/RAF mutations by ctDNA. Acneiform rash was the most commonly reported non-hematologic adverse event (up to 38.9%). No treatment-related deaths were reported. Conclusions: EGFRi rechallenge is associated with significantly longer OS and PFS than conventional systemic therapy and a clinically meaningful ORR in heavily treated patients with mCRC, particularly for patients with RAS/RAF-wild type mCRC tested right before EGFRi rechallenge.
Phase I/II trial of encorafenib, cetuximab, and nivolumab in microsatellite stable <i>BRAF</i> <sup>V600E</sup> metastatic colorectal cancer following progression on prior BRAF+EGFR targeted therapies.
Authors: Kelsey Pan, Yunyu Baig, Jason Willis, Arvind Dasari, Alisha Heather Bent, Victoria Higbie, Ryan W Huey, Bryan K. Kee, Michael Sangmin Lee, Christine Parseghian, Maria Pia Morelli, John Paul Y.C. Shen, Scott Kopetz, Van K. Morris
Journal: Journal of Clinical Oncology (2025)

182 Background: A BRAF V600E mutation, present in approximately 8-10% of all colorectal cancers (CRC), is a poor prognostic biomarker for patients with metastatic CRC. The BRAF V600E inhibitor encorafenib (E) and the anti-EGFR antibody cetuximab (C) are approved for refractory, BRAF V600E mCRC based upon on overall response rate (ORR) of 20% and median progression-free survival (PFS) of 4.2 months . A single-arm trial adding the anti-PD1 antibody nivolumab (N) to E+C in the same (BRAF-inhibitor naïve) population showed promising efficacy, with an ORR of 50% and median PFS of 7.4 months. We evaluated the efficacy of E+C+N in patients with microsatellite stable (MSS), BRAF V600E mCRC who had progressed on prior E+C. Methods: Patients with MSS, BRAF V600E mCRC with documented prior progression on E+C were eligible for treatment with E (300 mg PO daily), C (500 mg/m 2 q14 days), and N (480 mg IV q28days) were included in the study. Primary endpoint was best overall response by RECIST 1.1. Secondary endpoints were PFS, overall survival (OS), and toxicity (by CTCAE v5). Circulating tumor DNA assessment of molecular alterations in the MAPK pathway in association with response were performed by NGS. Descriptive statistics were used to summarize outcomes. Results: Among the 12 participants, none achieved a radiographic response, and 5 experienced stable disease. Disease control rate was 41.7% (95% CI, 13.8-69.6). Median PFS was 3.7 months (95% CI, 1.7-5.7), and median OS was 8.3 months (NE-NE). Four patients (16.7%) had concomitant MAPK-activating alterations at baseline, and APC , TP53 , and PIK3CA mutations were present in 25.0%, 66.7%, and 33.3% of patients, respectively. The presence of MAPK-activating mutation was not associated with disease progression (odds ratio 1.3; 95% CI 0.11-16; p=0.82). The most common grade 1-2 treatment-related adverse events (AEs) were anemia (N=5), arthralgia (N=5), rash (N=4), headache (N=4), and fatigue (N=3); 1 of the 12 patients experienced a grade 3 small bowel obstruction. Conclusions: In this pilot study, addition of N to E+C did not appear to overcome resistance to prior BRAF + EGFR targeted therapies in patients with MSS, BRAF V600E mCRC. While the addition of immunotherapy has demonstrated promising signal in early-phase clinical trials for this population, the benefit appears unlikely when offered sequentially after progression on BRAF combination therapies. Clinical trial information: NCT04017650 .