tbuckley/cabot-search huggingface dataset:
Is lymph node metastasis an event indicating an advanced gastrointestinal stromal tumor?
Authors: Peng Zhang, Weili Yang, Yingfeng Fu, Jun Zhang, Fan Feng, Gang Zhai, Yang Fu, Xin Wu, Xinhua Zhang, Xiao-Jun Wu, Zhidong Gao, Han Liang, Yanbing Zhou, Heli Liu, Kaixiong Tao
Journal: Journal of Clinical Oncology (2024)

754 Background: The clinicopathological features and prognosis of gastrointestinal stromal tumors (GISTs) with lymph node metastasis remain controversial owing to their low incidence. A multicenter retrospective cohort study was conducted to compare the clinicopathological features and oncologic outcomes of GIST with and without lymph node metastases. Methods: The medical records of patients with GISTs in 16 large medical centers in China from January 2014 to December 2020 were reviewed. Patients were divided into three groups: no metastasis, lymph node metastasis without distant metastasis, and distant metastasis without lymph node metastasis. Propensity score matching (PSM) was performed to reduce confounding factors. Results: A total of 1109 cases of primary GIST were included in this study, comprising 607 males (54.7%) and 502 females (45.3%), with a mean age of 56.6±11.9 years. There were 1024 patients (92.3%) with no lymph node metastasis after surgery, and 85 patients (7.7%) had lymph node metastasis. Compared to that in GIST without lymph node metastasis, the proportion of non-gastric GIST was higher in GIST with lymph node metastasis (52.9% vs. 40.7%) with a larger tumor diameter (&gt;10 cm: 36.5% vs. 18.1%) and more patients with distant metastasis (11.8% vs. 3.5%). Tumor location not in the stomach, the largest tumor diameter, and distant metastasis were independent risk factors for GIST with lymph node metastasis (all P &lt; 0.05). After PSM, 96, 48, 24 patients comprised no metastasis, lymph node metastasis without distant metastasis, and distant metastasis without lymph node metastasis, respectively. The relapse-free survival (RFS) of the lymph node metastasis group was comparable to that of the distant metastasis group without lymph node metastasis ( P = 0.368) and significantly inferior to that of no metastases ( P = 0.042). Conclusions: The prognosis of patients with GIST with lymph node metastasis was comparable to that of patients with distant metastasis and significantly worse than that of patients without metastasis. Lymph node metastasis may be an advanced event in GIST.
Frequency and oncologic outcomes of KRAS mutations in circulating tumor DNA of patients with pancreatic ductal adenocarcinoma.
Authors: Mahmoud M.G. Yousef, Mark W. Hurd, Abdelrahman M.G. Yousef, Rebecca A Snyder, Mark Knafl, Mohammad Mahdi Fanaeian, Ray Chacko, Jennifer Peterson, Brandon George Smaglo, Robert A. Wolff, Shubham Pant, Michael Sangmin Lee, Michael J. Overman, Ching-Wei D. Tzeng, Matthew H. G. Katz, Huamin Wang, Anirban Maitra, Ethan B. Ludmir, John Paul Y.C. Shen, Dan Zhao
Journal: Journal of Clinical Oncology (2024)

636 Background: KRAS genetic alterations have been reported in more than 90% of pancreatic ductal adenocarcinoma (PDAC). The association of KRAS mutation subtypes detected in circulating tumor DNA (ct-DNA) with survival remains unclear. We investigated the rate of liquid biopsy detected KRAS mutation subtypes, and their association with overall survival (OS) in patients with PDAC. Methods: The Foundry software platform was used to retrospectively query a single-institution Electronic Health Records to identify patients with PDAC who underwent ct-DNA liquid biopsy from 2018 to 2023 and extract their oncologic outcomes. Results: Liquid biopsies were performed for 313 patients with PDAC; 58% (n=181) were diagnosed with stage IV disease. The median follow-up was 25 months, with median OS 24 months (95%CI=21-29). Overall, 52% (n=162) tested positive for KRAS mutations. Among patients with metastatic disease at diagnosis (n=181), 66.7% (n= 120) tested positive for KRAS mutations. In contrast, only 31.8% (n= 42) of patients with stage I to III disease at diagnosis (n=132) tested positive. Among patients with metastatic disease, those with KRAS positive disease had significantly shorter OS (median OS 13 vs 27 months, HR=2.7, 95%CI=1.7-4.3, P&lt;0.0001). In patients with non-metastatic disease, the median OS was 28 vs 43 months, respectively (HR=1.7, 95%CI=0.97-2.8, P=0.064). The most frequent KRAS mutation was G12D (n=66, 40.7% of KRAS mutations) followed by G12V (n=58, 35.8%), G12R (n=15, 9.3%), and Q61H (n=10, 6.2%). Among KRAS mutations allelic subtypes, KRAS G12D and Q61 mutations had significantly worse OS with median OS 13 and 10 months respectively (P &lt;0.001). The most frequently co-occurring mutations detected in KRAS positive patients were TP53 (n=126, 77.8%), CDKN2A (n=34, 21%), SMAD4 (n=33, 20.4%), and ARID1A (n=12, 7.4%). Examining the prognostic significance of co-occurring mutations among patients with metastatic disease, only detection of co-occurring CDKN2A mutation was associated with worse OS as compared to patients with KRAS mutations without co-occurring CDKN2A mutations (median OS 8 vs 14 months, HR=2, 95%CI=1.1-3.5, P value=0.015). Conclusions: Detection of KRAS mutation in liquid biopsies of patients with metastatic PDAC is associated with worse OS. KRAS G12D/Q61 alterations detection is associated with worse OS compared to other KRAS mutation subtypes. Ct-DNA detection of co-occurring CDKN2A mutation is associated with worse OS in patients with KRAS positive metastatic disease.
Evaluating local tumor destruction and wedge or segmental resection in the treatment of fibrolamellar hepatocellular carcinoma: An NCDB analysis.
Authors: Christopher Reese Bine, Marco Braaten, Alec Czaplicki, Eric G. Nielsen, Aron Lee, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2024)

512 Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare type of hepatic cancer, comprising 1% of all liver malignancies. Patients are often diagnosed in their second or third decade and often have a palpable liver mass. Treatment primarily consists of surgery and transplant, however, standardized protocols have not been well established due to its rarity. For patients who cannot receive a transplant, there are few studies examining and comparing other surgical types. Using the National Cancer Database, we aim to uncover survival and patient characteristic differences between those who receive Local Tumor Destruction vs Wedge or Segmental Resection. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with FL-HCC from 2004 to 2019 using the histology codes 8171 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at α = 0.05. Results: Of the 803 patients in the sample,19 patients received Local Tumor Destruction (LTD) and 142 patients received Wedge or Segmental Resection (WSR). The average age of patients receiving LTD was 54 compared to 32 for WSR. WSR patients experienced longer overall survival than LTD (106 vs. 63 months respectively; p&lt;0.05). When controlling for age, year of diagnosis, tumor size, comorbidity score, and surgery type, WSR showed a greater decrease in overall hazard compared to LTD (HR=0.224 vs 0.306; p&lt;0.05). WSR use was highest in healthy patients with no co-morbidities, however, patients were also significantly more likely to have later stage tumors (II, III, and IV vs. stage I; p&lt;0.001). Despite being associated with a lower OS, LTD was utilized more commonly for earlier stage (stage I vs. II, III and IV; p&lt;0.001) and well differentiated tumors (p&lt;0.001). Compared to WSR, it was associated with higher rates of therapy before and after surgery(p&lt;0.05). There were no significant differences in tumor size, income group, adjuvant therapy type, or facility type (p&gt;0.05) between the treatment groups. Conclusions: Receipt of WSR is associated with improved survival compared to LTD. There are distinct demographic groups which may be guiding surgical selection. Further research into this disparity and other surgical types should be examined to create better guidelines for FL-HCC patients.
Initial uptake of durvalumab with or without tremelimumab for advanced hepatocellular carcinoma in routine clinical practice: Preliminary results of the international DT-real study.
Authors: Ciro Celsa, Naoshi Nishida, Ashwini Arvind, Susanna Varkey Ulahannan, Michael Li, Bernhard Scheiner, Claudia A.M. Fulgenzi, Antonio D'Alessio, Giulia F Manfredi, Bernardo Stefanini, Giuseppe Cabibbo, Alessio Cortellini, Matthias Pinter, Robin Kate Kelley, Paul Antoine El Tomb, Amit G. Singal, Masatoshi Kudo, David James Pinato
Journal: Journal of Clinical Oncology (2024)

501 Background: HIMALAYA trial showed that durvalumab plus tremelimumab (Single Tremelimumab Regular Interval Durvalumab; STRIDE) significantly improved overall survival (OS) and that durvalumab (DUR) was non-inferior compared to sorafenib in patients with hepatocellular carcinoma (HCC). However, real world outcomes on this regimen have not been described. Methods: In the context of a prospectively maintained database including 953 patients (pts) with unresectable HCC treated with immunotherapy, we analysed a subgroup of pts treated with STRIDE or DUR across 5 centres in USA, Asia and Europe. We assessed OS, progression-free survival (PFS), objective response rate (ORR) by RECIST 1.1 (per investigator) and treatment-related adverse events (TRAEs) per CTCAE v.5.0. Results: Between February and May 2023, 59 pts initiated treatment with STRIDE or DUR (mean age 67.2 years, male sex 81.4%). 33 pts (55.9%) were treated in first-line (1L) and 26 (44.1%) in second- or further-line (&gt;1L). STRIDE regimen was administered in 24 patients (40.7%): 6 pts in 1L, 18 pts in &gt;1L. Child-Pugh class was A in 32 pts (54.2%), being more common in pts treated with STRIDE than DUR (79.2% vs 37.1%, p=0.003). ECOG-PS was 0 in 35 pts (59.3%) and it was more common in pts treated with STRIDE than DUR (79.2% vs 47.0%, p=0.015). Outcomes are reported in Table. After a median follow-up of 3.2 months (95%CI 2.6-3.8), median OS was not reached and 6-month OS rate was 59.4%. In pts treated with STRIDE, median OS was not reached and 6-month OS rate was 95.8%, while median OS was 4.9 months (95%CI 3.2-4.9) for DUR. Median PFS was 2.5 months (95% CI 1.9-3.8) and ORR (evaluable in 43 pts, 72.9%) was 16.3% (95%CI 6.5-33.5%). Any grade TRAEs and grade 3-4 TRAEs were 42.4% (95%CI 27.4-62.5) and 10.2% (95%CI 3.7-22.1%), respectively. TRAEs requiring systemic corticosteroid therapy occurred in 3 pts (5.1%). Conclusions: Preliminary observational data from DT-real confirm uptake of STRIDE and DUR across various lines of therapy, with encouraging efficacy and safety outcomes in routine practice. [Table: see text]
Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and tislelizumab for unresectable hepatocellular carcinoma: A single-arm, phase II study.
Authors: Yongkang Xu, Shumin Fu, Ye Mao, Fengming Yi, Weiming Jiang, Long Feng, Jianbing Wu
Journal: Journal of Clinical Oncology (2024)

500 Background: Unresectable hepatocellular carcinoma (uHCC) patients (pts) had high unmet medical needs in practice. Retrospective studies suggested a potent antitumor effect and long-term survival benefit of hepatic arterial infusion chemotherapy (HAIC) plus programmed death-1 inhibitor and lenvatinib. This prospective phase II study aimed to evaluate the efficacy and safety of HAIC combined with lenvatinib and tislelizumab in uHCC pts. Methods: Eligible pts were aged ≥18 years and had histologically confirmed uHCC, ECOG PS ≤1, Child-Pugh (C-P) A/B, and ≥1 measurable lesion per RECIST 1.1. Pts received HAIC of modified FOLFOX (oxaliplatin, 85 mg/m 2 ; leucovorin, 400 mg/m 2 ; 5-fluorouracil bolus, 400 mg/m 2 on day 1; 5-fluorouracil infusion, 2400 mg/m 2 for 46 h), lenvatinib (8 or 12 mg once daily for body weight &lt;60 or ≥60 kg), and tislelizumab (200 mg every 3 weeks). HAIC was allowed to repeat on demands. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included ORR per mRECIST, disease control rate (DCR), surgical conversion rate, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: Between June 2021 and January 2023, 46 pts were enrolled. The median age of pts was 51-year-old, most were male 42 (91.3%), ECOG PS 0 33 (71.7%), C-P A 44 (95.7%), tumor diameter ≥10 cm 31 (67.4%), multiple tumors 33 (71.7%), vascular invasion 38 (82.6%), extrahepatic metastasis 7 (15.2%). As of August 15, 2023, . All pts entered efficacy and safety analysis, ORR was 52.2% (0 complete response [CR], 24 partial response [PR]) per RECIST 1.1; ORR was 84.8% per mRECIST, with 5 CR and 34 PR. DCR was 95.6% per either RECIST 1.1 or mRECIST. Surgical conversion rate was 21.7% (10/46). Median PFS was 10.9 (95% CI, 8.0-13.8) months; 12-month OS rate was 41.3%. COX analysis revealed that ECOG PS 1 (HR, 3.17; 95% CI, 1.43-7.03; p=0.005), multiple tumors (HR, 3.68; 95% CI, 1.22-11.14; p=0.021), and extrahepatic metastasis (HR, 4.04; 95% CI, 1.57-10.40; p=0.004) were independently associated with poor PFS. Any-grade AEs occurred in 43 (93.5%) pts, the most common were proteinuria (43.4%), aspartate aminotransferase (AST) increased (35.8%), and alanine aminotransferase (ALT) increased (32.1%). Grades ≥3 AEs occurred in 10 (21.7%) pts and mainly included AST increased (7.5%), hypertension (3.8%), and hyperbilirubinemia (3.8%). Conclusions: HAIC combined with lenvatinib and tislelizumab showed meaningful clinical benefits and acceptable safety in uHCC pts. The study is ongoing, OS will be reported later. Clinical trial information: ChiCTR2200064384 .
Qualification of major pathological response as a surrogate endpoint for relapse-free survival following neoadjuvant immunotherapy for hepatocellular carcinoma.
Authors: Antonio D'Alessio, Bernardo Stefanini, Julia Blanter, Benjamin Adegbite, Claudia A.M. Fulgenzi, Ciro Celsa, Giulia F Manfredi, Madhava Pai, Robert D. Goldin, Daniel Shu, Yung-Yeh Su, Marina Baretti, Robert A. Anders, Mark Yarchoan, Chiun Hsu, Thomas Urban Marron, David James Pinato
Journal: Journal of Clinical Oncology (2024)

506 Background: Neoadjuvant use of immune checkpoint inhibitors (ICI) is feasible and achieves pathological responses in a subset of patients with hepatocellular carcinoma (HCC). However, it is not clear whether pathological response to ICI translates into long-term survival benefit. Methods: We analysed patient-level data from 86 subjects recruited to 4 prospective phase I/II clinical trials of ICI prior to liver resection (LR) in 9 centres in the United States, Europe, and Asia and included a cohort of 23 patients (pts) receiving neoadjuvant ICI off trial. Radiological response was assessed with RECISTv1.1. Major (MPR) and complete pathological response (pCR) were considered as ≥70% and 100% non-viable tumour in the resected specimen, respectively. Pathological responses were correlated with radiologic overall response rates (ORR) and relapse-free survival (RFS). Results: Out of 109 pts treated between 10/2017 and 09/2023, 55 pts (50.5%) received a double ICI combination, 35 (32.1%) ICI monotherapy, and 19 (17.4%) an antiangiogenic/ICI combination. In 19 pts (17.4%) an adjuvant ICI course was administered for a median time of 5.5 months (m) (interquartile range [IQR] 3.7-6.0). Most of pts were male (77.6%) with underlying viral chronic liver disease (68.2%), performance status 0 (83.5%), BCLC 0-A (55%), a median tumour diameter of 6.0 cm (IQR 3.9-9.9) without portal vein thrombosis (75.7%). After a median follow-up of 27.3 m (95% CI 21.5-33.0), 35 (32.1%) relapses and 14 (12.8%) deaths occurred. Radiologic ORR was 28.5% (n=31), with 3.7% complete responses (CR, n=4) and 24.8% partial responses (PR, n=27). Out of 100 pts evaluable for a pathological response, 33% achieved MPR and 19% pCR. MPR was more likely in patients who had achieved a radiologic PR or CR (82%) as compared to those who did not (14% p&lt;0.001), however linear correlation suggested an imperfect correlation between ORR and MPR (R 2 0.43, p&lt;0.0001). Median RFS was 43.5m (95%CI, 27.5-59.6), while median overall survival was not reached (NR). mRFS was significantly improved in pts with MPR (NR vs 28.3m [95%CI, 13.1-43.5], hazard ratio [HR] 0.27 [95%CI, 0.11-0.69], p = 0.003) and with pCR (NR vs 32.8m [95%CI, 15.2-50.4], HR 0.20 [95%CI, 0.05-0.82], p=0.013). Conclusions: This study is the first to qualify the role of MPR as a putative surrogate endpoint for recurrence-free survival in pts treated with neoadjuvant immunotherapy for HCC. Validation in larger phase III clinical trials is warranted.
Use of tumor-informed ctDNA across gastrointestinal cancers.
Authors: Matthew Reilley, Paul Raymond Kunk, Tri Minh Le, Muneeb Rehman
Journal: Journal of Clinical Oncology (2024)

758 Background: In colorectal cancer (CRC), the use of ctDNA for the purpose of early recurrence detection and prognostication is established, and multiple studies are testing its utility for guiding adjuvant therapy decisions. Tumor informed testing can be performed in clinical situations where adequate tissue is available for next-generation sequencing (NGS). Increasingly, ctDNA testing is being used clinically for colorectal cancer patients and other gastrointestinal (GI) cancers when there is an appropriate clinical scenario and adequate tumor tissue is available for sequencing. Methods: We identified GI cancer patients treated at our institution where Signatera (Natera) testing was ordered and performed between 2020 – 2023. We included all patients for whom testing was ordered. Then, among patients with any result further analyzed results by disease type, stage, and results. We examined clinical rationale for testing and whether results informed subsequent decisions. Results: A total of 99 GI cancer patients for whom ctDNA testing was ordered were identified. 80 patients had at least 1 ctDNA result including 68 colorectal patients and 12 other GI cancers (anal, bile duct, esophagogastric, pancreatic, and small bowel). Among patients with measurable ctDNA, at the most recent testing timepoint 16 had levels that met criteria for positive detection, while 64 were undetectable. Most commonly, testing was ordered in stage II/III CRC patients for post-operative surveillance. Other clinical use scenarios included 1) surveillance/treatment monitoring in oligometastatic CRC, 2) surveillance in non-metastatic esophagogastric cancer, 3) treatment monitoring in MSI-H/immunotherapy sensitive GI cancers. For at least 18 patients, results were a factor in shared clinical decision making between patients and providers. Conclusions: We found ctDNA monitoring is most commonly used in the adjuvant setting for CRC patients which is best supported by existing studies. Our data demonstrates that tumor informed testing can be successful in other GI cancers for both surveillance and therapy monitoring. Given the broad and rapid adoption of this technology, there needs to be continued efforts for both prospective validation studies and retrospective real world studies to guide clinical practice.
Nutritional impact and prognostic role of systemic inflammatory response index (SIRI) in advanced pancreatic cancer: PANTHEIA-Spanish Society of Medical Oncology (SEOM) study results.
Authors: Vilma Pacheco-Barcia, Axel Mariño Méndez, Alberto Carmona-Bayonas, Javier Gallego, Carles Fabregat Franco, Jorge Adeva, Paula Cerdà, Luis Cabezon-Gutierrez, Sara Custodio-Cabello, Ismael Ghanem, Irene Hernandez, Angela Lamarca, Berta Laquente, Ana López-Alfonso, Nieves Martinez Lago, Teresa Macarulla, Inmaculada Peiro, Laura Visa, Paula Jimenez-Fonseca, Andrés Muñoz
Journal: Journal of Clinical Oncology (2024)

623 Background: Whilethe systemic inflammatory response assessed by SIRI has been recognized as a prognostic factor in advanced pancreatic cancer, understanding its association with patients' nutritional status may provide deeper insights into disease biology and outcomes. Methods: This is an observational, non-interventional and multicenter study (15 Spanish hospitals) promoted by SEOM, including retrospective and prospectively patients with metastatic pancreatic cancer in routine clinical practice. Clinical and nutritional data was recorded, and SIRI was calculated using the formula: (neutrophils x monocytes) / lymphocytes. We considered SIRI score as low (SIRI-L) or high (SIRI-H) using a cutoff of &lt;2.3 or ≥2.3, respectively based in our previous findings. PANDORA-SEOM tool was used for electronic data collection. The main outcome is to correlate SIRI with the nutritional status. Other aims were to correlate the overall survival (OS) and progression-free survival (PFS) with SIRI and weight loss in the 3 months prior to diagnosis using the Kaplan-Meier method and multivariate Cox regression model. Data from the pilot study is presented in this abstract, and more data is expected to be available prior to the Congress. Results: We included 144 patients retrospectively: 65% men, with median age of 66 years (range 45-81). The most common 1 st line chemotherapy regimen were gemcitabine + nab/paclitaxel (63.2%), mFOLFIRINOX (20.1%) and FOLFOX (11.8). Prior to diagnosis, 54.2% of patients had weight loss &gt;5 Kilograms (Kg) and 22.9% lost &gt;10 Kg. SIRI-H was significantly associated with weight loss &gt;5Kg compared to SIRI-L, 35.7 vs 24% respectively (p=0.028). Patients with a pretreatment SIRI-H showed shorter OS compared to SIRI-L (median OS 5 vs 12 months, Hazard Ratio (HR) 3.047, 95% Confidence Interval (CI) 2.069-4.488, p&lt;0.001), as well as shorter PFS (median PFS 5 vs 10 months, HR 2.364, 95% CI 1.650-3.387, p&lt;0.001). In the patient subgroup that experienced &gt;5Kg weight loss, SIRI-H was associated with worse OS (median OS 4 vs 12 months). We didn’t find an association between CA19.9 level and SIRI or weight loss. Multivariate analysis identified SIRI as an independent prognostic factor for OS (HR 2.962, 95% CI 1.911-4.591, P&lt;0.001). Conclusions: Our findings underscore the importance of SIRI as a significant predictor of nutritional status and disease aggressiveness in patients with metastatic pancreatic cancer. Prospective data will help us to validate these findings.