tbuckley/cabot-search huggingface dataset:
Perioperative versus adjuvant therapy in resectable pancreas cancer.
Authors: Tianyi Wang, Jamie N Mills, Brandon Ellsworth, Brian Griffith, Valerie Gunchick, Thomas Enzler, Oxana V. Crysler, Kyle Cuneo, Hari Nathan, Theodore Steven Lawrence, Mark Zalupski, Clifford Cho, Vaibhav Sahai, Filip Bednar
Journal: Journal of Clinical Oncology (2025)

703 Background: Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer death in the United States with a 5-year survival rate of 13%. Recurrence rates are high following resection and optimization of neoadjuvant and adjuvant therapy remains under investigation, with the hypothesis that neoadjuvant/perioperative therapy may convert borderline resectable tumors to resectable and prevent progression of micro-metastases in the postoperative setting. Our study evaluates patient outcomes and models predictive and prognostic markers to assist with clinical decision-making in consideration of neoadjuvant therapy for resectable and borderline resectable pancreatic cancers. Methods: We performed a single-institution retrospective analysis of patients who underwent pancreatic resection between January 1, 2016 and December 31, 2020 (n=532). We excluded patients with unresectable disease or a non-PDAC diagnosis. Analysis of the remaining patients (n=175) was performed using automated and manual chart review, basic statistical comparisons with T-tests or Chi-squared tests, Kaplan-Meier Survival analyses, and Cox Proportional Hazard Testing using intention to treat analysis. Results: There were no significant differences (p&gt;0.05) the presenting demographics between the adjuvant (AJ, n=97) and neoadjuvant/perioperative (NP, n=76) groups. Patients were more likely to have a history of pancreatitis, a risk factor for PDAC development, in the NP group (p=0.0153). Patients in the AJ group included patients who ultimately did not receive the recommended adjuvant therapy for various reasons (n=25) and had overall worse performance status (p=0.004) and received less chemotherapy overall compared to the NP cohort (p=0.0003). Adjuvant therapy was more likely to be gemcitabine with capecitabine (n=37, p=0.0007) in the AJ group and gemcitabine with nab-paclitaxel (n=11, p=0.0018) in the NP group. In the neoadjuvant setting, 62% of patients received FOLFIRINOX and 28% received gemcitabine with nab-paclitaxel. Patients in the NP group were more likely to receive radiation (p=0016), including 6 patients who received neoadjuvant radiation. Median overall survival (33.9 [28.8-43.8] versus 38.2 [28.2-47.8] months) and progression free survival (21.1 [18.1-34.2] versus 16.6 [11.7-23.6] months) were not significantly different between the AJ and NP groups, respectively. Conclusions: These results demonstrate similar presenting characteristics between patients with resectable PDAC treated in a period when general practice shifted from adjuvant therapy to a neoadjuvant/perioperative approach. Although patients treated neoadjuvantly received more chemotherapy overall and the chemotherapy regimens differed between the groups, patients had similar outcomes in the two groups.
Investigation of the association of <i>CTRB2</i> exon 6 deletion with time to progression and overall survival in pancreatic ductal adenocarcinoma.
Authors: Zafar A Siddiqui, Khalid Jazieh, Jason Hoskins, Kari G. Rabe, Samuel O Antwi, Hugues Sicotte, Erin E. Carlson, Ann L. Oberg, Katelyn Connellly, Ryan Michael Carr, Laufey Amundadottir
Journal: Journal of Clinical Oncology (2025)

770 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and limited treatment options. A 584 bp deletion in CTRB2 , which impairs chymotrypsin B2 function, has been linked to increased PDAC risk. This study investigates the impact of this deletion on progression and survival outcomes in patients with PDAC. Methods: There were 633 patients in whom CTRB2ex6 deletion was genotyped; 263 patients received chemotherapy and had time to progression (TTP) information. TTP was calculated from diagnosis date until earliest of 1) progression date (event), 2) surgery, death, or next chemotherapy date (competing risk), or 3) date last known to be alive (censor). Overall survival (OS) was calculated for the cohort from diagnosis until date of death (event) or date last known to be alive (censor). TTP was analyzed using cumulative incidence methods accounting for competing risks; OS was analyzed using Kaplan-Meier methods. Cox proportional hazard models adjusted for age and sex were used to test associations and compute hazard ratios (HR) and 95% confidence intervals (CI). Results: Median TTP in those with CTRB2ex6 deletion negative carrier status (n=209) was 1.3 years vs 5.9 years for those with positive carrier status (n=54). Estimated 3-year progression rates were 54.2% for patients with no CTRB2ex6 deletions, 43.7% for patients with one deletion (n=48), and 33.3% for patients with two CTRB2ex6 deletions (n=6). TTP was not associated with CTRB2 deletion carrier status (HR: 0.8, 95% CI: 0.6-1.3). Median OS for CTRB2ex6 deletion negative carriers (n=514) was 1.0 year vs 0.9 years for positive carriers (n=119); within deletion carriers, heterozygous carriers (n=110) had a median OS of 0.9 years, and homozygous carriers (n=9) had a median OS of 2.6 years. OS was not associated with CTRB2 deletion carrier status (HR: 1.0, 95% CI: 0.9-1.3). Conclusions: Although we did not detect statistically significant differences in TTP and OS by CTRB2ex6 deletion carrier status, there was an interesting trend toward longer TTP and OS in the small number of patients who carried homozygous CTRB2ex6 deletions. Larger studies are warranted to validate these findings.
Phase II study of neoadjuvant FLOT and chemoradiation for trimodality therapy of esophageal/GEJ adenocarcinoma.
Authors: Jeffrey R. Olsen, Alexis Diane Leal, Sunnie S. Kim, Karyn A. Goodman, David Binder, Matthew Blum, Crystal Erickson, Robert John Hoyer, Douglas Jerome Kemme, Christopher Hanyoung Lieu, Arthur Liu, Megan Marsh, Lynn Mathew, Martin McCarter, Wells A. Messersmith, Joshua H. Petit, Daniel Shonebarger, Timothy V Waxweiler
Journal: Journal of Clinical Oncology (2025)

466 Background: Recent data support use of perioperative FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) chemotherapy over pre-operative chemoradiation (CRT) for patients with resectable esophageal/GEJ adenocarcinoma with limited studies evaluating combined FLOT/CRT. This prospective phase II study (NCT04028167) evaluated a neoadjuvant approach of FLOT followed by CRT for resectable esophageal/GEJ adenocarcinoma (EAC). Methods: Operable patients with cT1-2 N1-2 or cT3-4N any4 Nany non-metastatic EAC were eligible. Neoadjuvant treatment consisted of FLOT x 3 cycles followed by restaging PET and chemoradiation (41.4 Gy / 23 fractions to the primary site and regional lymphatics with weekly carboplatin/paclitaxel). Adjuvant nivolumab for non-pathologic complete response (pCR) was permitted. The primary endpoint was pCR rate among patients receiving the study regimen and undergoing resection, with secondary endpoints including disease free survival (DFS), overall survival (OS), toxicity, and correlative studies. DFS/OS was measured using the Kaplan Meier (KM) method. Interim results are presented after a planned safety analysis. Results: Since 4/2020, 23 patients with median age of 62 (range 40-73) have enrolled. cT3-4 and cN+ disease was present in 20/23 (87%) and 16/23 (70%) of patients, respectively. FLOT was completed by 21/23 patients (reasons for discontinuation included allergic reaction and G5 sepsis/endocarditis). All 21 patients initiating chemoradiation completed planned treatment and 17/21 underwent resection (2 refused surgery after achieving cCR, 1 died of cardiac arrest, 1 patient is awaiting surgery). A pCR was observed in 5/17 resected patients (29%), with pCR or near pCR observed in 9/17 (53%). The complete response rate (pCR + cCR for patients refusing surgery) was 7/19 (37%). Adjuvant nivolumab was administered in 9 patients. The median follow-up among all patients was 20 months with 2-year DFS and OS estimates of 61% and 73%. The regimen was tolerated with G3+ hematologic, G3+ gastrointestinal, and G3+ other toxicity observed in 39%, 13%, and 22% of patients, respectively. Conclusions: In a locoregionally advanced population, neoadjuvant sequential FLOT followed by CRT was well tolerated with encouraging DFS/OS and a high rate of complete response compared to prior studies. This hybrid platform may enhance both locoregional and distant control and is of interest for expanded evaluation. Clinical trial information: NCT04028167 .
Fruquintinib combined with PD-1 inhibitors and chemotherapy in the first-line treatment of HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma (FDZL-FIX): A single-arm, open-label phase 2 study.
Authors: Chenchen Wang, Mingzhu Huang, Yuedi Dai, Wanjing Feng, Xiaoying Zhao, Xiaodong Zhu
Journal: Journal of Clinical Oncology (2025)

461 Background: For unresectable locally advanced or metastatic HER2-negative gastric cancer (GC), the combination of chemotherapy with immunotherapy, specifically PD-1 inhibitors, has emerged as a new standard of care in first-line treatment of advanced GC, but the patients’ outcomes remain poor. Early clinical studies investigating the combination of immunotherapy with anti-angiogenic drugs have demonstrated favorable efficacy. Therefore, it is worth exploring whether the addition of fruquintinib, a potent VEGFR-1,2,3 inhibitor, to the combination of PD-1 inhibitor and chemotherapy can further enhance the survival benefits for patients with unresectable locally advanced or metastatic HER2-negative GC. Methods: This is an open-label, single-center clinical study. The enrolled patients were all no less than 18 years old with HER2 negative locally advanced unresectable or metastatic gastric or gastrooesophageal junction adenocarcinoma, without any systemic anticancer treatment for advanced disease. Eligible patients received 6 cycles of combined first line treatment with fuquinitinib (4mg daily, d1-14, q3w, oral) combined with PD-1 inhibitor (sintilimab 200mg or nivolumab 360mg intravenously q3w) and chemotherapy (XELOX or SOX) regimen. The following maintenance treatment was fuquinitinib combined with PD-1 inhibitor and S-1/capecitabine until disease progression or intolerable toxicity. The primary endpoint was progress free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), duration of response (DoR), disease control rate (DCR) and safety. Results: At the cutoff date on Sep 18, 2024, a total of 27 patients were enrolled and received at least one dose of treatment. 23 patients had received the response evaluation, with an ORR of 60.9% (14/23; 95%CI 38.5-80.3) and DCR of 100% (23/23 95%CI 85.2-100.0). In the intention to treatment (ITT) population, the median PFS was 9.79 months (95% CI 5.29-NA). Safety profile indicated that 22.2% (6/27) experienced grade≥3 adverse events. The most common grade ≥ 3 adverse reactions mainly include neutropenia (7.4%, 2/27) and thrombocytopenia (7.4%%, 2/27). Conclusions: The combination of fruquintinib and chemotherapy with PD-1 blockade in the first-line treatment for unresectable locally advanced or metastatic HER2-negative GC had shown promising efficacy and acceptable safety profile. Enrollment in the trials is still ongoing. Clinical trial information: NCT06158919 .
Phase II study of cabozantinib and nivolumab in refractory metastatic microsatellite stable (MSS) colorectal cancer (CRC).
Authors: Alexis Diane Leal, Patrick Jud Blatchford, Sunnie S. Kim, Robert William Lentz, Douglas Jerome Kemme, McKenna Russen, Tyler Friedrich, Lynn Mathew, Robert John Hoyer, Scott Arthur Kono, Emily Baiyee Toegel, Stacey M Bagby, Adrian Dominguez, S. Lindsey Davis, Todd Pitts, Christopher Hanyoung Lieu, Wells A. Messersmith
Journal: Journal of Clinical Oncology (2025)

229 Background: Current data suggest that combining tyrosine kinase inhibitors with immune checkpoint inhibitors may be a promising treatment strategy in patients with metastatic MSS CRC. This prospective, open-label, single-arm, phase II study (NCT04963283) evaluated the efficacy of cabozantinib in combination with nivolumab in patients with metastatic refractory MSS CRC. Methods: Patients with metastatic/unresectable MSS CRC who were refractory to chemotherapy in the 3 rd line setting and beyond were eligible. Patients were treated with cabozantinib 40 mg orally daily and nivolumab 480 mg IV every 28 days. Tumor assessments were obtained every 8 weeks for the first 16 weeks, and then every 12 weeks thereafter. Response was assessed via RECIST v1.1. The primary endpoint was 16-week disease control rate (16-wk DCR); secondary endpoints were objective response rate (ORR), progression free survival (PFS), overall survival (OS), safety and tolerability, and correlative studies (to be presented at a future date). Results: Between June 2021 and January 2024, 49 pts were enrolled; 63% were male; median age 55 [50-64]. Median prior treatment regimens were 4 [2-14]. Most patients (84%) had not received prior trifluridine/tipiracil; only 1 patient had received prior regorafenib. The 16-wk DCR was 40% (19/47) (95% CI 0.264 – 0.557). The 16-wk ORR was 8.5% (4/47) (95% CI 0.024 – 0.204). mPFS was 3.4 months (95% CI 1.8-5.0) and mOS was 10.9 months (95% CI 4.7-13.8). Thirty nine percent of patients experienced a serious adverse event (SAE), with 4% Gr 1, 37% Gr 2, 35% Gr 3 and 4% Gr 4; there were no Gr 5 treatment related adverse events. The most common AEs were diarrhea (53%), fatigue (43%), hypothyroidism (31%), weight loss (29%), nausea (29%), and hypertension (27%). Two patients remain on study at time of abstract submission. Conclusions: The combination of cabozantinib and nivolumabwas well tolerated and provided modest benefit in a population of patients with metastatic, chemotherapy refractory, MSS CRC. Clinical trial information: NCT04963283 .
Prediction of immunotherapy response in deficient mismatch repair colorectal cancers using an immune-enhanced exome and transcriptome platform.
Authors: Frank A. Sinicrope, Bahar Saberzadeh-Ardestani, Anupama gupta, Rondell P. Graham, Jason T Lewis, Charles Abbott, Sean Michael Boyle
Journal: Journal of Clinical Oncology (2025)

270 Background: While immune checkpoint blockade (ICB) is used to treat metastatic deficient mismatch repair (dMMR) colorectal cancers (CRCs), such tumors are heterogeneous and resistance to ICB is frequent. To date, biomarkers that can consistently predict patient response to ICB are lacking. We determined whether biomarkers that integrate tumor and immune-related molecular mechanisms could predict ICB response. Methods: Consecutive patients with metastatic dMMR CRCs (N=32) who had been treated with anti-PD-1 therapy were proﬁled using a validated immune-enhanced exome and transcriptome platform (ImmunoID NeXT, Personalis) using tumor and paired normal tissue. This platform provides antigen-specificity of T or B cells, indicated by the TCR or BCR respectively, neoantigen prediction, tumor mutation burden (TMB), immune profile, HLA allele-speciﬁc loss of heterogeneity (LOH) and a Neoantigen Presentation Score (NEOPS) that combines a neoantigen prediction tool with mechanisms of immune evasion. Tumor variables were analyzed in relationship to objective tumor response, and a Cox proportional hazards model was fit to predict progression-free survival (PFS) or overall survival (OS). Results: In CRCs, TCR and BCR repertoire diversity were each significantly increased in tumors from responders versus those with stable or progressive disease after anti-PD-1 treatment (p=0.015 and p=0.048, respectively). Neoantigen burden score, TMB, and HLA allele-speciﬁc LOH (reflects loss of antigen presentation machinery) were each unable to distinguish responders from nonresponders. An immune checkpoint gene expression signature was increased in nonresponders relative to responders (P= 0.005). Neoantigen presentation score (NEOPS) was prognostic when adjusted for tumor grade only for OS (p=0.048). Conclusions: The T-cell and B-cell receptor (TCR/BCR) repertoire, as well as NEOPS, were each significantly predictive of favorable response to anti-PD-1 therapy in dMMR tumors. In addition, an immune checkpoint gene expression signature was predictive of resistance to ICB.
Investigating the real-world outcomes of single- versus multi-agent preoperative chemoradiotherapy for locally advanced rectal cancer: NCDB analysis from 2004-2020.
Authors: Gaurav Sharma, Justin Boyd, Alana Bell, Gannon Ray, Ahmed Abdalla
Journal: Journal of Clinical Oncology (2025)

61 Background: Fluorouracil-based chemoradiotherapy is the standard initial treatment for locally advanced rectal cancer, demonstrating improved pathological response and reduced local recurrences compared to radiation alone. Fluorouracil-based chemo-radiation therapy has no impact on distant recurrences. Oxaliplatin was tested in addition to fluorouracil-based chemo-radiotherapy in clinical trials to improve pathological complete response (pCR), distant recurrence-free survival, and overall survival. The trial results are conflicting. In this study, we aim to compare single-agent (SA) versus multi-agent (MA) chemotherapy using real-world data from the National Cancer Database (NCDB). Methods: The NCDB was used to identify 39,667 patients with rectal cancer who received concurrent chemoradiotherapy between 2004 and 2020. We compared patients who received SA chemotherapy with those who received MA concurrent chemotherapy. The primary outcomes of interest were overall survival and pCR. The groups were compared using univariate analysis and Cox proportional hazard models to adjust for potential confounding factors. Results: Of 39,667 patients with rectal cancer, 24,452 received single-agent (SA) chemotherapy and 14,215 received multi-agent (MA) chemotherapy. Patients in the SA group were of advanced age, had a greater number of comorbidities (as calculated by the Charleson-Dayo score), were treated within community facilities, had a higher income status, were covered by government insurance, were situated on the east coast, and had lower educational attainment compared to those in the MA group (p&lt;0.05). SA group had higher T4 and N1 disease, however MA group had more N2 disease. Upon survival analysis, patient in MA group had higher survival (41.2 vs 38.9 months, p=0.005), however pCR was significantly higher in SA group (10.4% vs 6.4%, p&lt;0.001). Conclusions: MA chemoradiotherapy for rectal cancer improves survival, with the SA regimen showing enhanced complete pathological response. Differences in baseline characteristics may explain the outcomes. While MA chemotherapy offers modest overall survival benefits, potential toxicity needs to be considered and confirmed in future studies. Comparison between single agent vs multi-agent chemo-radiotherapy group. Outcome Single-agent chemotherapy Multiagent chemotherapy Chi Squared p-value No readmission within 30 days of surgical discharge 22,727 (89.3 %) 12,921 (90.9 %) &lt;0.001 30-day mortality after surgery 360 (1.5 %) 59 (0.5 %) &lt;0.001 90-day mortality after surgery 716 (3.0 %) 158 (1.3%) &lt;0.001 Median duration of surgical admission 6.0 5.0 &lt;0.001 Median survival-vital = deceased (months) 38.9 41.2 0.005 Median survival-vital = alive (months) 66.9 52.0 &lt;0.001 Pathological complete response (pCR) 2,644 (10.4%) 904 (6.4%) &lt;0.001
Development and regulatory approval of a new systemic targeted therapy for advanced hepatocellular carcinoma.
Authors: Boris Pasche, Al B. Benson, Masatoshi Kudo, Anthony F. Shields, Hugo Jimenez, Asfar S. Azmi, Alexandre Barbault
Journal: Journal of Clinical Oncology (2025)

613 Background: There are no commercially available devices for the treatment of patients with advanced hepatocellular carcinoma who have failed 1st line and 2nd line therapy. We have identified tumor-specific modulation frequencies in patients with advanced hepatocellular carcinoma. We exposed patients to radiofrequency electromagnetic fields, which are amplitude-modulated from 0.1 Hz to 100 kHz and measured changes in pulse pressure. Frequencies eliciting measurable changes in pulse pressure were selected as tumor-specific frequencies. Methods: Treatment is administered to patients with advanced hepatocellular carcinoma by means of a battery-operated portable device emitting 27 MHz radiofrequency electromagnetic fields, which are amplitude-modulated at hepatocellular carcinoma frequencies. The device is connected to a coaxial cable ending with a spoon-shaped antenna placed on the anterior part of the patient's tongue during treatment. Treatment is administered three times a day for one hour. Results: A total of 69 patients with advanced hepatocellular carcinoma received treatment with the TheraBionic device until progression or death. The median overall survival of patients who received treatment with the TheraBionic device after failing 1st line and 2nd line therapy was 9.15 (95% CI 1.6-34.8) months and the median overall survival of Child-Pugh A patients was 9.5 months, which are comparatively longer than the 7.8 months pooled estimated medians of the placebo arms of 11 randomized 1st line and 2nd line placebo-controlled studies assessing the safety and efficacy of new agents for the treatment of Child-Pugh A advanced HCC (Llovet, Montal et al., J Hepatol 2019). We also analyzed the survival of patients who had received two lines of systemic therapy and did not receive any additional cancer treatment while and after receiving treatment with the TheraBionic device. The median OS of these patients was 9.8 months and the median OS of the Child-Pugh A patients was 17.2 months, which are comparatively longer than the 7.74 months pooled estimated medians of the placebo arms of the above cited 11 randomized studies. To assess unknown device-related adverse events, we assessed patient reported symptoms using the same scale in the SHARP and Asian Pacific Sorafenib studies. The incidence of any grade adverse events among Child-Pugh A who received treatment with the TheraBionic device was not different from the Placebo group of the SHARP and Asian Pacific Sorafenib studies. There were no NCI Grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient developed grade 1 fatigue. Conclusions: The data presented here provide reasonable assurance of safety and probable benefit in patients with advanced hepatocellular carcinoma who have failed 1st line and 2nd line therapy: https://www.fda.gov/medical-devices/recently-approved-devices/therabionic-p1-h220001 .