bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in pancreatic cancer incidence and mortality in the United States from 2000 to 2019: A SEER-based study.
Authors: Abidoye Oluseyi , Cho Young Min , Ahoussougbemey Mele Ange , Bhushan Sheena , Ruiz Vega Ruben , Ghosh Aditya Kumar 
Published: January 2023

755 Background: The annual incidence and mortality rates of pancreatic cancer has been rising. We analyzed pancreatic cancer trends by demographics and geographic location. Methods: Data obtained from the Surveillance, Epidemiology, and End Results (SEER) registry 17 were available to assess trends of pancreatic cancer incidence and mortality from 2000 to 2019. Results: The pancreatic cancer incidence and mortality rates consistently increased over time from 2000 to 2019. Incidence of pancreatic cancer was highest in males (14; 95% Cl, 13.9,14.1) and blacks (15.4 95% Cl,15.2, 15.6). The incidence was highest in Alaska (16.2; 95% Cl, 14.1, 18.5), and lowest in Utah (10.7; 95% Cl, 10.4, 11.0). Incidence increased at 0.85% per year (95% Cl, 0.76, 0.92; P < .001). Overall incidence increased significantly for all sex, race, stage sub-groups except for Blacks (APC of 0.04%; 95% Cl, -0.14, 0.22; P = 0.649), and American Indian/Alaska natives (APC of -0.22 %; 95% Cl, -1.33, 0.89; P = 0.679). There was an overall significant increase in incidence across all states except for Alaska. Incidence-based mortality of pancreatic cancer was highest in males (12.6; 95% Cl, 12.5,12.7) and blacks (14.1; 95% Cl, 13.9, 14.3). Mortality was highest in Alaska (15.1; 95% Cl, 13.1,17.3), and lowest in Utah (9.6; 95% Cl, 9.3,9.9). Mortality increased at 0.91% per year (95% Cl, 0.32, 1.50; P = .005). The overall incidence-based mortality increased significantly only in the males APC, 0.95% (95% Cl, 0.36, 1.54; P = 0.003), females APC 1.18 (95% Cl, 0.47, 1.89; P = 0.002) and whites APC 1.05% (95% Cl, 0.45, 1.66; P = 0.002). Furthermore, there was an overall significant increase in incidence-based mortality across all states except for Alaska, Hawaii and Washington. Conclusions: Pancreatic cancer incidence and mortality rates increased overall but differed by demographics and geographic location.
Spectrum of germline mutations among Mexican patients with colorectal cancer.
Authors: Aguilar Dione , Santuario Facio Sandra , Barraza Angélica , Villarreal-Garza Cynthia , Ortiz Lopez Rocio 
Published: January 2023

78 Background: Colorectal cancer (CRC) is the third most common cancer in the world, and the second most frequent cause of death due to cancer. 5-10% of CRC cases are due to a hereditary predisposing syndrome, the most frequent being Lynch Syndrome (LS) followed by Familial Adenomatous Polyposis (FAP), characterized by loss of function of mismatch repair genes (MMR) and APC, respectively. The purpose of this study is to describe the spectrum of germline pathogenic variants among Mexican CRC patients using Next-generation sequencing (NGS). Methods: This study is original research approved by IRB; all patients signed the informed consent. 43 patients between 18-60 y/o with CRC were enrolled. NGS was performed using a panel which targeted a set of 94 genes and 284 SNPs known to play a role in cancer predisposing. Bioinformatics data analysis was carried out using Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE) and an in-silico analysis to classify variants according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Mean age 48.71 y/o, 62.6% men. Germline pathogenic and likely pathogenic variants (PV/LP) were identified in 69% of sample. A molecular diagnosis of LS (MLH1, MSH2, MSH6, and PMS2) was confirmed in 12 (28%), and FAP in 5 (11.6%). It is remarkably the presence of 5 PV in PRF1 (2 G149S; 3 A91V), among other unusual genes for CRC. Also 12 double heterozygotes were identified, including one with PRF1 and CHEK2 PV. Conclusions: NGS allow the discover of new pathogenic variants that would not be suspected in classic hereditary syndromes. The understanding of other genes involved in other pathways could expand our understanding in the heritability of CRC. PRF1 emerges as a new candidate gene associated with CRC, previous evidence supports the role of PRF1 in solid tumors beside hematologic malignancies.
The role of socioeconomic deprivation in gastrointestinal cancer clinical trial enrollment at an NCI-designated comprehensive cancer center.
Authors: Strebig Daniel , Al-Toubah Taymeyah E. , Coughlin Emily , Mhaskar Rahul , Lowery Sylea , Mathew Ebin , Capelli Mitchell , Pattnaik Aishwarya , Turner Kea , Kirtane Kedar , Dhahri Amina , Kim Richard D. , Permuth Jennifer B. , Vadaparampil Susan Thomas , Fleming Jason B. , Strosberg Jonathan R. , Powers Benjamin Daniel 
Published: January 2023

785 Background: Socioeconomic deprivation has been described as a barrier to cancer clinical trial participation. However, few studies have examined socioeconomic deprivation using patient-level or granular geocoded designations. To overcome this challenge, the Area Deprivation Index (ADI) was used to assess neighborhood socioeconomic deprivation in a cohort of gastrointestinal cancer clinical trial patients at an NCI-Designated Comprehensive Cancer Center. Methods: Patients enrolled in a gastrointestinal cancer clinical trial from 2008 to 2019 with an identifiable ADI national rank were identified. Socioeconomic deprivation was assessed using the ADI, a publicly available, validated dataset that ranks census block groups into percentiles using variables such as income, education, employment, and housing characteristics. For this study, ADI was categorized as quintiles listed in the table. Statistical analyses included Chi-square and Kruskal-Wallis tests. Results: The median age of the cohort (N=1,334) was 62.0 years. Most patients were male (54.3%). Race included White (88.2%), African American (6.8%), and Asian (1.5%) patients. Hispanic/Latinx patients made up 6.7% of the cohort. The median ADI was 46. The proportion of enrollees from lowest to highest ADI quintile was 11.2%, 29.3%, 27.3%, 19.1%, and 13.1%. Trial enrollment differed by ADI and age (p=0.019), gender (p=0.042), race (p<0.001), and insurance (p=0.001). Conclusions: In this study, patients enrolled in gastrointestinal cancer clinical trials had lower neighborhood socioeconomic deprivation than the national or state average. African American, Hispanic/Latinx, female, and uninsured patients comprised a lower proportion of enrollees compared to catchment area estimates (10.6%, 17.7%, 51.3%, and 12.4%, respectively). These findings suggest inequity in clinical trial enrollment and warrant further studies to identify drivers of these disparities. [Table: see text]
Effect of tumor location on the efficacy of chemotherapy for gastrointestinal stromal tumors.
Authors: Sweeney Ryan , Shah Shivani , Wegner Rodney E. 
Published: January 2023

790 Background: Gastrointestinal stromal tumors (GISTs) arise from multiple sites within the gastrointestinal tract. Since the introduction of imatinib in 2002, patients have seen improved overall survival. However, a recent National Cancer Database (NCDB) study suggested no survival benefit to adjuvant imatinib for colorectal GIST patients. Another recent study showed that small bowel GISTs have larger median tumor size and higher incidence of tumors with at least 5 mitoses compared to gastric GISTs. These findings suggest a differential tumor biology for GISTs arising from different primary tumor sites, potentially conferring differential response to imatinib. In this NCDB study, we compare overall survival outcomes with and without chemotherapy, stratifying by primary tumor site. Methods: We queried the NCDB from 2004-2018 for patients with GIST histology. We excluded patients with age <40, age>80, high comorbidity score, and patients who received additional therapy other than surgery or chemotherapy. Of the 22,846 patients meeting criteria for our study, 27 patients had tumors originating from the anus, 454 from the colon, 173 from the esophagus, 15,296 from the stomach, 556 from the rectum, 32 from the rectosigmoid junction, and 6,308 from the small intestine. 8,983 (39%) received chemotherapy. Treatment with chemotherapy was used to extrapolate response to imatinib, the mainstay of treatment. Results: Cox proportional hazards analysis demonstrated increased hazard of death for chemotherapy, increasing age, and comorbidity score of 1. Positive predictive factors for survival included female sex and later year of diagnosis. For anal, esophageal, gastric, and rectosigmoid GIST patients, there was no statistically significant overall survival benefit for any treatment modality. For colonic GISTs, neoadjuvant chemotherapy combined with surgery improved overall survival. For rectal GISTs, adjuvant chemotherapy with surgery also provided survival benefit. For small intestinal GISTs, surgery alone or surgery with neoadjuvant, adjuvant, or both neoadjuvant and adjuvant chemotherapy improved overall survival. Conclusions: While our study is retrospective and limited as a NCDB study, our Kaplan-Meier survival analysis demonstrated survival benefit for chemotherapy only in patients with colon, rectal, or small intestinal GIST tumors. Our Cox proportional analysis demonstrated an overall negative survival impact for chemotherapy. These findings lend further support to the idea that differential tumor biology at each primary site may lead to differential response to imatinib. Overall, our study provides rationale for further investigating the heterogeneity of GIST tumor microenvironments, as these differences could contribute to the differential treatment outcomes.
Improvement of a clinical colorectal cancer risk prediction model integrating polygenic risk.
Authors: Spaeth Tuff Erika Leigh , Gafni Aviv , Dite Gillian S. , Allman Richard 
Published: January 2023

81 Background: Improving colorectal cancer risk prediction and stratification is pivotal for implementing better screening and prevention programs in public health and for enabling a personalised approach for assessing patients’ colorectal cancer risk. Methods: In this study, we used the UK Biobank to compare the performance of a risk prediction model incorporating two different polygenic risk scores – one comprising 45 SNPs and the other comprising 140 SNPs. The clinical component of the risk prediction model included a simple measure of first-degree family history. We used age- and sex-specific population incidence rates to calculate full-lifetime risks. Results: The model using the 140-SNP PRS showed an improvement in discrimination, calibration and risk stratification over the model using the 45-SNP PRS for full-lifetime risk: discrimination was 0.706 (95% CI 0.697–0.715) and 0.674 (95% CI 0.664–0.683), respectively, and the P for difference was < 0.001. The 140-SNP model was well calibrated and showed a small overestimation of risk 0.951 (95% CI 0.918–0.986). Standard incidence ratios compared to population incidence rates showed that, for the 140-SNP model, the top quintile of risk shows a 27% improvement compared to the 45-SNP model. Furthermore, there was a 3-fold difference in colorectal cancer incidence between adults identified in the top quintile compared to the bottom quintile of risk using the 140-SNP model versus the 45-SNP model. Conclusions: This updated risk prediction score with a 140–SNP PRS and a simple measure of family history, improves risk prediction and risk stratification in the general population compared with a similar model with a 45-SNP PRS, and will ultimately assist in colorectal cancer disease prevention in the clinic.
Randomized phase II trial of encorafenib and cetuximab with or without nivolumab for patients with previously treated, microsatellite stable, BRAFV600E metastatic and/or unresectable colorectal cancer: SWOG S2107.
Authors: Morris Van K. , Guthrie Katherine A , Kopetz Scott , Breakstone Rimini , Karasic Thomas Benjamin , Hu Zishuo Ian , Bellasea Shay , Fakih Marwan , Gholami Sepideh , Gold Philip Jordan , Philip Philip Agop 
Published: January 2023

TPS265 Background: Patients with microsatellite stable (MSS), BRAFV600E metastatic colorectal cancer (mCRC) experience poor survival outcomes. Treatment with the BRAF inhibitor encorafenib (E) and anti-EGFR antibody cetuximab (C) is an approved treatment combination, with a reported overall response rate (ORR) of 20% and median progression-free survival (PFS) of 4.1 months. Anti-PD-1 antibodies like nivolumab (N) are ineffective as monotherapy for patients with MSS, BRAFV600E mCRC. In preclinical models of MSS, BRAFV600E CRC, inhibition of BRAF and EGFR induces a loss of expression of mismatch repair genes and promotes a microsatellite instability-high phenotype, which may prime these tumors for response to immunotherapy. In support of these findings, a single-institution clinical trial of E + C + N for 26 patients with MSS, BRAFV600E mCRC reported an ORR of 50% and median PFS of 7.2 months. We hypothesize that the addition of N to E + C will improve median PFS for patients with MSS, BRAFV600E mCRC. Methods: In this prospective phase II clinical trial (N = 75), patients with previously treated MSS, BRAFV600E mCRC will be randomized 2:1 into 2 arms, respectively: experimental treatment (E + C + N) or standard treatment (E + C). No prior BRAF, EGFR, or immunotherapy agents are allowed. All patients will receive E (300 mg PO daily) and C (500 mg/m2 IV every 14 days), and patients in the experimental arm will receive N (480 mg IV every 28 days). The primary endpoint is PFS. Secondary endpoints include overall survival, best overall response, duration of response, and safety/tolerability. Using a one-sided α = .10 and power 80%, we target an improvement in median PFS from 4.2 to 7.3 months and a hazard ratio of 0.57. Additional patient specimens will be collected for exploratory correlative research. The study activated across the United States in June 2022 and as of September 2022 has enrolled 2 of 75 planned participants. Funding: NIH/National Cancer Institute grants U10CA180888, U10CA180819, U10CA180820, U10CA180821, U10CA180868; and in part by The Hope Foundation for Cancer Research STrS award. Clinical trial information: NCT05308446 .
An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab and bevacizumab therapy in patients with locally advanced unresectable or metastatic hepatocellular carcinoma.
Authors: Bekaii-Saab Tanios S. , Yarchoan Mark , Ahmed Muneeb , Cohan David Michael , Ma Wen Wee 
Published: January 2023

TPS623 Background: Despite advances in treatment for unresectable hepatocellular carcinoma (HCC), long-term survival rates remain poor. The combination of bevacizumab (Bev) and atezolizumab (Atezo) is the preferred frontline therapy for advanced HCC, but a minority of patients (pts) respond, and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment, mediated by activated immune checkpoint signaling and angiogenesis pathways, which may contribute to therapeutic resistance. RP3 is a genetically modified herpes simplex virus 1 (HSV-1) that expresses the fusogenic GALV-GP R- protein, an anti–CTLA-4 antibody-like molecule, CD40 ligand, and 4-1BB ligand. The direct oncolytic effect coupled with immune stimulation by RP3 in the tumor microenvironment is intended to provide systemic anti-tumor activity and reverse therapeutic resistance to anti-PD-1/PD-L1 agents. Pre-clinical data has demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev supporting the clinical combination of RP3 with Bev. RP3 combined with anti-PD1 therapy has demonstrated clinical activity and safety in pts with various malignant solid tumors. This study will evaluate the safety and efficacy of RP3 combined with Atezo and Bev as 1st (1L) and 2nd (2L) line systemic therapies for inoperable and advanced HCC. Methods: The 1L and 2L cohorts will each enroll up to 30 pts with advanced, unresectable HCC. Pts in the 1L cohort may not have received prior systemic treatment; pts in the 2L cohort must have progressed on or following one prior line of systemic therapy, which must have included a PD-(L)1 directed agent. Key inclusion criteria include advanced unresectable HCC with at least 1 measurable tumor of ≥1 cm in longest diameter, Childs-Pugh Class A, and ECOG Score of 0 or 1. Important exclusion criteria include untreated esophageal and/or gastric varices with bleeding or at high risk for bleeding, and macroscopic invasion of tumor into major blood vessels and/or main bile ducts. Pts with a history of medically refractory hepatic encephalopathy and/or hepato-renal syndrome are also excluded. Pts in 1L cohort will receive 1200 mg Atezo and 15mg/kg Bev Q3W together with RP3 intratumorally (IT) Q3W for a total of up to 8 doses. In 2L pts will receive RP3 Q2W for 4 doses with Bev Q3W starting on C1D1, then RP3 and Bev Q3W for up to 4 more doses with Atezo Q3W being added on C4D1. The primary endpoint includes overall response rate (ORR) by RECIST v1.1. Secondary endpoints are safety, ORR using HCC mRECIST, duration of response, complete response rate, and progression-free survival.
A phase 1b, open-label, safety, pharmacokinetic, and pharmacodynamic study of an anti–super-enhancer triptolide analogue with nab-paclitaxel plus gemcitabine in patients with metastatic adenocarcinoma of the pancreas.
Authors: Park Joon Oh , Hong Jung Yong , Kim Seung Tae , Park Young Suk , Saluja Ashok 
Published: January 2023

TPS769 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies and the leading cause of cancer-related death in the world, although recent advances in chemotherapies for metastatic PDAC provide better clinical outcomes. Triptolide (TPL), a natural compound isolated from the Chinese herb has shown promising antitumor activity though the inhibition of HSP70 in a number of preclinical models including pancreatic cancer. In addition, TPL disrupt super-enhancer networks in pancreatic cancer cells and cancer-associated fibroblasts to reprogram the cellular cross talk and signaling in tumor environment. Minnelide (ML), water soluble, novel prodrug of TPL, was recently reported to show promising activity in patients with gastrointestinal malignancies in phase I trial. Based on the strong synergism with nab-paclitaxel (A) plus gemcitabine (G), we designed this phase 1b study. Methods: Eligible patients will have histologically confirmed PDAC and have failed first-line FOLFIRINOX with adequate organ function and performance status. This study is composed of two parts; dose escalation and dose expansion. In the dose escalation part (phase 1b), different dose levels of ML (0.25 mg to 1.0 mg once a day) in combination with A plus G will be tested with 3+3 subjects recruited in each cohort. Patients in each cohort will receive ML 0.25 to 1.0 mg orally once a day on days 1-5, 8-12 and 15-19 with A 100-125mg/m2 intravenously plus G 800-1000mg/m2 IV on days 1, 8 & 15 of a 28-day cycle. The primary endpoint is to determine the safety of ML with A+G and to determine PFS by Independent Radiological Review (IRR). Once an MTD reaches, a total of 18 patients will be enrolled at MTD level in dose expansion part. The key secondary endpoints are to determine the pharmacokinetics, pharmacodynamics effect, the percentage of patients who achieve an objective confirmed overall response by IRR, maximum tolerated dose and recommended dose for phase 2 of ML in combination of A+G. As of September 2022, the study is just initiated for patient enrollment in first cohort. This study is prospectively registered on ClinicalTrials.gov, NCT05557851. Clinical trial information: NCT05557851 .
A phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI Study).
Authors: Rogers Sherise C. , Sahin Ilyas , Fabregas Jesus C. , Nassour Ibrahim , Ramnaraign Brian Hemendra , Hitchcock Kathryn , Hughes Steven J. , Lee Ji-Hyun , Kayaleh Omar Roger , Turk Anita Ahmed , Fan Z. Hugh , Russell Karen Bullock , DeRemer David L. , George Thomas J. 
Published: January 2023

TPS778 Background: Neoadjuvant treatment for potentially curable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Liposomal irinotecan injection (Nal-IRI) is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PDAC. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen (NALIRIFOX) and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase 2, open-label, multicenter single-arm study focuses on patients (pts) with operable PDAC without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multidisciplinary GI tumor board (resectable vs. borderline), adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive NEO-N-IRI regimen as per Table every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30-day postoperative complication rate. Microbiota specimens will be collected for exploratory analysis. Clinical trial information: NCT03483038 . [Table: see text]