bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue factor (TF) and factor VII/TF ratio (fVIIa:TF) as potential indicators of malignancy in pancreatic cystic lesions.
Authors: Haque Farzana , Featherby Sophie , Broughton Laura , Lykoudis Pavlos , Wedgwood Kevin , Dasgupta Dowmitra , Khulusi Sam , Ra Abdul , Buchanan Alexander , Huang Chao , Nikitenko Leonid , Ettelaie Camille , Maraveyas Anthony
Published: January 2023

669

Background: Premalignant pancreatic cellular genotype may remain stable for many years, but compounding conditions can produce rapid malignant cellular transformation. This onset is rarely spontaneous and is often associated with the presence of inflammation. One inflammatory modulator is “tissue factor (TF),” which usually acts in complex with “coagulation factor VIIa (fVIIa)” to initiate coagulation. The role of TF in malignancy and its impact beyond thrombosis on cell proliferation, angiogenesis, and metastasis is well established. This suggests that TF may be a diagnostic marker in the inflammatory microenvironment of the precursor lesions of pancreatic cancer. Aim: To examine the potential of TF concentrations and the fVII:TF ratio within pancreatic cyst fluid as indicators of malignant cellular transformation from benign to malignant. Methods: Cyst fluid was prospectively collected from 31 patients with pancreatic cystic lesions (REC 18/LO/0736) and analysed in a blinded fashion. The level of TF and fVIIa proteins were measured by ELISA, and the fVIIa:TF ratios calculated. A cut-off value for TF concentration was determined using a ROC curve and compared to the conventional assessment parameters, including radiological features, carcinoembryonic antigen (CEA) and amylase. Results: Patients were categorised into four groups based on histology. Significant histological stage-dependent increases in TF level were observed, which corresponded to the progression of the normal ductal epithelium to invasive adenocarcinoma. The mean TF concentration was significantly higher ( p= 0.006) in the high-risk group (high-grade dysplasia & malignant; 1.17 ng/ml, 95% CI 0.68, 1.67) vs the low-risk group (benign & low-grade dysplasia; 0.27 ng/ml, 95% CI 0.1, 0.44). A strong positive correlation between TF concentration and the high-risk group was observed (correlation coefficient 0.746, p < 0.001, the cut-off value for TF 0.75 ng/ml, AUC 0.877, p= 0.002). In addition, the fVIIa:TF ratio, was marginally lower ( p= 0.274) in the high-risk group (mean = 84.82 [95% CI 0, 185.04]) vs the low-risk group (mean = 437.46 [95% CI 0, 901.02]). TF concentrations performed consistently better as an indicator of malignant transformation when compared to the conventional parameters and will be presented at the meeting. Conclusions: Cyst-associated TF levels appear to correlate with the cytological progression to the malignant phenotype, while the fVIIa:TF ratio indicates a breakdown in the ability of the body to contain the disease. Such indicators may allow better presurgical discrimination of malignant potential of tumours and offer a more nuanced tool for monitoring indeterminate cystic lesions. Further work is needed with a larger cohort to confirm these findings.
Clinical therapeutic effects of neoadjuvant chemotherapy in resectable pancreatic cancer.
Authors: Murakawa Masaaki , Takahashi Daishi , Kawahara Shinnosuke , Kamioka Yuto , Yamamoto Naoto , Tezuka Shun , Kobayashi Satoshi , Ueno Makoto , Morimoto Manabu , Oshima Takashi , Yukawa Norio , Rino Yasushi , Morinaga Soichiro
Published: January 2023

677

Background: Results from the phase III Prep-02/JSAP-05 trial demonstrated the efficacy and safety of gemcitabine plus S-1 as neoadjuvant chemotherapy for resectable pancreatic cancer. However, consensus on neoadjuvant chemotherapy for pancreatic cancer has not yet been established, and the effects of neoadjuvant therapy on clinical features of the tumor and improvement in prognosis have not been fully investigated. We aimed to investigate the effect of neoadjuvant chemotherapy on resectable pancreatic cancer. Methods: Between 2013 and 2021, 291 patients who underwent curative resection for resectable pancreatic cancer at our hospital were enrolled. The patients were categorized into groups of those who received neoadjuvant chemotherapy (NAC group: n = 91) and those who received up-front surgery (US group: n = 200). Prognostic predictors were examined in (i) all patients, (ii) US group, and (iii) NAC group. Statistical significance was considered at p < 0.05. Results: The median follow-up periods were 20.7 and 33.2 months in the NAC and US groups, respectively. In the NAC group, 84 of the 91 patients (94.5%) received gemcitabine-based chemotherapy, and three (3.3%) received chemoradiotherapy. There was no difference in overall survival (OS) and recurrence free survival (RFS) between the two groups. In the background, the NAC group had lower preoperative CA19-9 levels, lower lymph node ratio (LNR), and smaller tumor size than in the US group. During multivariable analysis of OS, preoperative CA19-9 levels, LNR, modified Glasgow prognostic score (mGPS), resection margin, and tumor size were identified as possible prognostic predictors in all patients and in the US group, whereas LNR and mGPS were identified in the NAC group. Conclusions: The prognostic significance of preoperative CA19-9 level, tumor size, and LNR were counteracted in the NAC group. These findings may indicate the effect of neoadjuvant chemotherapy for resectable pancreatic cancer.
Analysis of survival outcomes in patients with pancreatic cancer who underwent upfront surgery.
Authors: Jung Jae Hyup , Park Jinkyeong , Ahn Jinwoo , Kim Bomi , Jung Kwangrok , Lee Jong-Chan , Hwang Jin-Hyeok , Kim Jaihwan
Published: January 2023

679

Background: During the last decade, the survival outcomes of patients with pancreatic cancer (PC) have improved. We aimed to establish a model of which clinical factors contributed to improved survival in PC patients who underwent upfront surgery. Methods: Public data from the KOREA Health Insurance Review and Assessment (HIRA) database were collected. Medical records in a single tertiary center were also retrospectively reviewed between 2013 and 2018. Enrolled patients were those who underwent curative upfront surgery for PC. Results: A total of 12,146 patients in HIRA data and 267 patients in single-center data were collected. The overall survival (OS) rates have improved over the years in HIRA data and were reproduced in single-center data. Dividing the patients of single-center data into two periods (2013-2015 [119] vs. 2016-2018 [148]) based on the results of public data, the median OS was significantly different between the two periods (20.9 vs 32.1 months, p=0.003). According to multivariate regression analyses, young age (≤70 years), R0 resection, negative nodal involvement, adjuvant treatment, and palliative chemotherapy with FOLFIRINOX or gemcitabine plus nab-paclitaxel (GNP) were significantly associated with better OS. A survival prediction model was created using the beta-coefficients in cox regression analysis of the above five significant factors, and the c-index by bootstrap validation (resampling, 1500) was 0.7088. The weight scores were as follows: Age >70 years, 1; R1 resection, 1; pN1, 1; pN2 stage, 3; no adjuvant treatment, 2; palliative chemotherapy with FOLFIRINOX and/or GNP, 3; without FOLFIRINOX or GNP, 5; no palliative chemotherapy, 5. Conclusions: Regarding the survival trends in patients with resected PC, we presented the recent improvement in survival over the years and suggested several clinical factors that contributed to it by different weights. Further studies are necessary for validation.[Table: see text]
Impact of patient characteristics and treatment patterns on outcomes in potentially resectable pancreatic cancer (PC).
Authors: Steinmetz Andrew , Patel Sameer H. , Wilson Gregory C. , Sussman Jeffrey J. , Olowokure Olugbenga Olanrele , Kharofa Jordan , Ahmad Syed A. , Sohal Davendra
Published: January 2023

681

Background: Treatment of PC remains a challenge, with surgery being the mainstay of potentially curative therapy. Even after surgical resection, however, many patients experience recurrence. There has been a shift toward treating PC as a systemic disease from diagnosis with neoadjuvant chemotherapy (nCT) or chemoradiation (nCRT). This study examines characteristics of real-world patients who were deemed to have resectable (R) or borderline resectable (BR) disease, and how they relate to overall survival (OS). Methods: This is a retrospective analysis of patients in an academic health system who presented for initiation of treatment for PC staged as R or BR. Descriptive data on patient characteristics, performance status (PS), laboratory values, neoadjuvant therapies, recurrence, and mortality were obtained. OS was evaluated using Kaplan-Meier analysis and log-rank tests. Two-sided p-values were calculated. Results: From electronic records at the University of Cincinnati, 129 patients were identified. Median age was 66 with baseline ECOG PS of mostly 0 (86, 67%) or 1 (40, 31%). Primary tumor site was most commonly head of pancreas (104, 81%). Of 129, 55 (43%) patients received surgery upfront; the rest received neoadjuvant therapy (39 nCRT, 35 nCT) with gemcitabine (68%) or 5-fluorouracil (32%) containing regimens. Of those receiving nCRT/nCT, 36 (49%) went on to resection; the rest experienced progression (27, 36%) or toxicities (11, 15%) including death. Of 129, 92 (71%) have died, with median OS of 20.1 months (95% CI 16.4 - 25.0) for the full cohort. On adjusted multivariable analysis, the following were associated with worse OS: failure to undergo resection (HR 5.65, 95% CI 3.17 - 10.09, p<0.0001); receiving <3 cycles nCT (HR 3.00, 95% CI 1.38 - 6.53, p=0.006); baseline CA 19-9 >100 (HR 2.73, 95% CI 1.52 - 4.90, p=0.001); BR disease (HR 2.20, 95% CI 1.27 – 3.81, p=0.005); not receiving RT (HR 1.91, 95% CI 1.04 - 3.53, p=0.038). Regimen choice was not associated with OS. Conclusions: In this real-world PC dataset, surgical resection remains the mainstay of curative therapy. Inadequate nCRT/nCT lead to suboptimal outcomes, likely reflecting patient physiology and disease biology effects. Future trials should focus on maximizing neoadjuvant therapy with the goal of resection.[Table: see text]
Racial, ethnic, and sex-based disparities among high-risk individuals undergoing pancreatic cancer surveillance.
Authors: Klute Kelsey , Lucas Aimee L. , Brand Randall , Everett Jessica N. , Farrell James J. , Hawthorne Kieran , Kaul Vivek , Kupfer Sonia S. , Paiella Salvatore , Simeone Diane M. , Sussman Daniel A. , Zogopoulos George , Kastrinos Fay , Katona Bryson W ,   and the PRECEDE Consortium
Published: January 2023

687

Background: The international, multi-center Pancreatic Cancer Early Detection (PRECEDE) Consortium enrolls high-risk individuals (HRIs) undergoing pancreatic ductal adenocarcinoma (PDAC) surveillance. Enrollment began in 2020, and despite challenges related to the COVID-19 pandemic, the PRECEDE Consortium rapidly accrued a large cohort of HRIs. The purpose of this study is to describe the characteristics of this cohort and assess racial, ethnic, and sex-based disparities. Methods: The PRECEDE Consortium (NCT04970056) is a prospective, multicenter study focused on improving survival from PDAC through early detection. Data from all HRIs who met criteria for PDAC surveillance and enrolled between May 2020 - March 2022 were collected and included in the analysis. Results: During the study period, 1299 HRIs enrolled in PRECEDE at 32 centers. HRIs were excluded if enrollment data was incomplete or criteria for PDAC surveillance were not met. Of 1113 who were included, 47.2% met criteria for familial pancreatic cancer (FPC) and 45.4% had a family history of PDAC along with a PV in a PDAC-risk gene (BRCA1, BRCA2, PALB2, ATM, MLH1, MSH2, MSH6, PMS2, or EPCAM). The remainder had familial atypical mole melanoma syndrome (5.7%), Peutz-Jeghers syndrome (1.6%), or hereditary pancreatitis (0.2%). More females than males enrolled (65.9% vs. 33.5%). The distribution of HRIs by race and ethnicity is depicted; the majority identified as white (87.7%). Study participants were primarily from the US (82.7%), the median age was 61 (27-85) and 18.5% had Ashkenazi Jewish ancestry. Nearly all HRIs consented to allow access to imaging data (99.6%), collection of germline DNA (97.7%), and biosample collection (99.5%). There were no race, ethnicity, or sex-based differences in rates of consent for collection of imaging, DNA, or biosamples. Conclusions: Enrollment of HRIs in prospective studies of PDAC surveillance is essential for advancing early detection research in PDAC. A distinct advantage of the PRECEDE Consortium for examining enrollment disparities is that recruitment began in 2020, providing a unique and current snapshot of the international PDAC surveillance landscape. Despite the recent attention on addressing disparities in healthcare delivery, significant racial, ethnic, and sex-based disparities persisted in the cohort of HRIs enrolled in the PRECEDE Consortium. Ensuring that the diversity of participants in the PRECEDE Consortium mirrors the communities served by participating centers is crucial. Further examining and addressing the reasons for these disparities is a major focus of the PRECEDE Consortium moving forward. [Table: see text]
Use of glycoproteome profiles to detect advanced adenomas and colorectal cancer.
Authors: Desai Khushbu , Mitchell Alan , Shah Ankita , Chandrasekar Dharini , Xu Gege , Lindpaintner Klaus , Serie Dan , Pearce Tillman E. , Hommes Daniel
Published: January 2023

69

Background: Colorectal cancer (CRC) remains a leading cancer despite current screening modalities. Precancerous lesions, or Advanced Adenomas (AA), commonly precede invasive cancer development by years. Newer technologies use circulating tumor DNA and/or proteins for CRC detection but have not been able to effectively detect AA. Aberrant protein glycosylation is associated with (pre-)malignant lesions. To detect glycoproteome profiles associated with the occurrence of AA, we studied serum glycoproteins in AA/CRC. Methods: A novel platform combining liquid-chromatography/mass-spectrometry (LC-MS) and artificial-intelligence (AI)-powered data processing allowing high resolution, high throughput glycoproteomic profiling was used to identify glycoprotein biomarkers in peripheral blood. Samples were sourced from biorepositories and included patients diagnosed with CRC, AA, ulcerative colitis (UC) and controls. The samples were split into a training (50%) and a hold-out testing set (50%) for the development of a machine learning (ML)-based multivariable predictive model. Statistical analysis was performed on normalized data to identify biomarkers differentiating AAs and different stages of CRC from controls. Results: We studied 563 patient samples: 196 controls (mean age 51.7; 52% female); 32 AA (mean age 68.6; 53% female); 247 CRC (mean age 65.6; 50% female) and 88 UC (mean age 44.1; 47% female). There were 250 differentially abundant (FDR < 0.05) glycopeptides/peptides when comparing CRC and AA samples with healthy and UC controls. A subset was assessed, generating a six (6) biomarker ML classification model. This model was applied to the hold-out test and achieved an overall sensitivity of 91.4% and specificity of 91.8% for predicting AA/CRC versus healthy/UC with an area under the receiver operating characteristic of 0.962. AA and CRC separately were predicted with a sensitivity of 84.4% and 92.8%, respectively, relative to healthy/UC with sensitivities for CRC stage 1/2 and stage 3/4 being 91.2% and 93.2%, respectively). Conclusions: Glycoproteomic serum profiles accurately detect precancerous AA in addition to CRC and offer a new approach to effective CRC screening. We will have completed an interim analysis of a large prospective observational study at the time of the meeting. Clinical trial information: NCT05445570 . [Table: see text]
Assessment of an emergency 14-day (d) integrative supportive care program (14-EISCP) followed by early chemotherapy (CTx) in symptomatic patients (pts) with advanced pancreatic ductal adenocarcinoma (aPDAC): A prospective ARCAD cohort study.
Authors: Rousseau Benoit , Falcoz Antoine , Toullec Clemence , Lecomte Thierry , Lambert Aurélien , Tournigand Christophe , Guerin-Meyer Veronique , Louvet Christophe , Trouilloud Isabelle , Rinaldi Yves , Coriat Romain , Dauba Jerome , Neuzillet Cindy , Andre Thierry , Bachet Jean-Baptiste , Cros Jerome , De La Fouchardiere Christelle , Garcia-Larnicol Marie-Line , De Gramont Aimery , Hammel Pascal
Published: January 2023

700

Background: Pts with aPDAC often have general health impairment due to high symptom burden at diagnosis. We investigated prospectively the clinical benefit (CB) of an EISCP followed by CTx as early as suspicion of aPDAC in pts with ECOG performance status (PS)≥2. Methods: In this multicenter study, PS≥2 pts with pathologically confirmed or suspected aPDAC on imaging were included at first oncology visit (V1) in a personalized 14-d EISCP including pain, nutritional, diagnostic/stenting procedures. Post-EISCP PS≤1 pts received mFOLFIRINOX or gemcitabine(Gem)/Nab-paclitaxel(NP), PS≥2 received mFOLFOX7 or investigator choice CTx or best supportive care (BSC). The primary endpoint was the 14-EISCP success on both feasibility of procedures within 14-d±2 and CB defined by post-EISCP PS≤1, ≥5 points improvement of either fatigue/pain/global health EORTC QLQ-C15-PAL quality of life (QOL) scores, or CTx start ≤30d, aiming 59% success for clinical relevance. Secondary endpoint included uni/multivariate median overall survival (mOS) analyses. Results: As of 07/2022, 106 pts were included; 93 pts were evaluable for primary endpoint: male 46%, mean age 74 yrs, PS2/3 79%/21%, metastases (M1) 62%, pathological diagnosis needed 53%, biliary stenting 16%. V1 mean QOL global health score was 48±23. mOS was 4.1 months (IC95 2.8-5.7). The 14-d feasibility was achieved in 71%. Post-EISCP CB was observed in 82% of pts: 13%, PS improvement to 0/1, 23% QOL improvement and/or 73% CTx start ≤30-d. Eight pts (9%) died during the EISCP. The primary endpoint was achieved in 59% of pts (n=55). Overall, 17 pts (16%) received mFOLFIRINOX/GemNP, 32 (30%) FOLFOX, 29 (27%) Gem or 5FU alone, and 28 (27%) BSC. OS analyses are shown. At d30, pts receiving CTx had a mean change of QOL global health score from 51±23 to 60±23. Conclusions: In PS≥2 pts with aPDAC, a personalized 14-EISCP is feasible and lead to a meaningful CB allowing the administration of doublet/triplet CTx in nearly half of the pts. Pts starting CTx within 30d had improved OS. Clinical trial information: NCT02979483 . [Table: see text]
Camrelizumab combined with apatinib and albumin-bound paclitaxel followed by camrelizumab plus apatinib as first-line therapy for unresectable or metastatic pancreatic cancer.
Authors: Shen Bo , Wu Yuan
Published: January 2023

703

Background: Pancreatic carcinoma has complex immunosuppressive tumor microenvironment that acts to insulate the tumor against an effective cytotoxic immune response. Apatinib (small molecular agent targeting the VEGFR-2), has shown the potential additive or synergistic antitumor effects with camrelizumab (anti-PD-1 agent) in vitro study. The inhibition of VEGF signaling pathway could trigger immune suppression provoked. Considering the anti-PD-1 agent plus antiangiogenic drug might avoid the substantial cumulative toxicities and obtain well tolerance, the specific and optimized therapeutic agents and treatment strategy to carry out chemotherapy-free strategy as maintenance or sequential (switch maintenance) therapy is hopeful and noteworthy. Methods: In this single-arm, single-center, exploratory study, patients (pts) who were pathologically or cytologically diagnosed as unresectable or metastatic pancreatic cancer and had not received systemic treatment before, with an ECOG performance status of 0-2. Pts received camrelizumab (200 mg intravenously once every 3 weeks) plus albumin-bound paclitaxel (125 mg/m2 intravenously on day 1,8 every 3 weeks) and apatinib (250 mg once daily orally on days 1–21 of each 3-week cycle) for 4–6 cycles, and pts without progressive disease (PD) after completing 4–6 cycles of initial camrelizumab plus albumin-bound paclitaxel and apatinib were administrated subsequent camrelizumab (200 mg intravenously once in 3 weeks) plus apatinib (250 mg once daily orally on days 1–21 of each 3-week cycle). Primary endpoint was progressionfree survival (PFS) by RECIST 1.1. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: From 09/2021 to 08/2022 13 pts were enrolled (median age 60, 77% male). At data cutoff, 5 pts continued to receive subsequent camrelizumab plus apatinib, 12 pts were included in the efficacy analysis. The ORR was 16.7%, with confirmed 2 (16.7%) PR. SD were 9 (75.0%) with a DCR of 91.7%. All pts experienced treatment-related AEs (TRAEs), the ≥grade 3 TRAEs were GGT increased (31%), blood bilirubin increased (8%), alanine aminotransferase increased (8%), aspartate aminotransferase increased (8%), alkaline phosphatase increased (8%), creatinine increased (8%), hypoesthesia (8%) and malaise (8%). Of 13 patients, 5 (38%) had TRAEs leading to any treatment interruption, and 5 (38%) patients had TRAEs leading to any dose reduction, respectively. None patient died because of TRAEs. Conclusions: Camrelizumab combined with apatinib and albumin-bound paclitaxel followed by camrelizumab plus apatinib demonstrated encouraging antitumor activity and manageable toxicity as firstline therapy for patients with unresectable or metastatic pancreatic cancer. Clinical trial information: ChiCTR2100045844 .
Incidence and clinical characteristics of patients with LAPC and mesenteric vein thrombosis and current treatment paradigm.
Authors: Zureikat Amer H. , Pishvaian Michael J. , Lopez Charles D. , Meredith Kenneth , Zervos Emmanuel E. , Hatoum Hassan , Chung Ki Y. , Tsobanoudis Alex , Berg Daniel James , Ucar Antonio , Nazemzadeh Reza , Bates Susan Elaine , Goodman Karyn A. , Johnson Thor , Parikh Nainesh , Kouri Brian , Laing Christopher , Boone Brian A. , Qureshi Imtiaz , Agah Ramtin
Published: January 2023

714

Background: Mesenteric venous thrombosis (MVT), defined as complete occlusion of the Superior Mesenteric Vein (SMV) or Main Portal Vein (MPV) is often incidentally identified on CT or MRI in patients with Locally Advanced Pancreatic Cancer (LAPC). There is very limited data describing the incidence and treatment of MVT in large studies in this patient population. Herein, we seek to establish the incidence of MVT and the treatment response in patients with LAPC. Methods: We conducted an analysis on 180 subjects with interpretable baseline imaging for MVT enrolled in the randomized Phase III TIGeR-PaC clinical trial (NCT03257033). Subjects who completed 4 Cycles of induction treatment (3 cycles of IV gemcitabine/nab-paclitaxel and 1 cycle of IMRT or SBRT) prior to randomization were analyzed. Baseline and end of induction CT scans were read by a board-certified radiologist to determine presence of MVT. Severe MVT was defined as complete occlusion of MPV and/or SMV. For patients who completed induction the end of induction CT was used to assess down staging of MVT. We analyzed the mean age between patients with and without MVT using a Mann-Whitney test and performed a contingency table with Pearson Chi-Square statistics to analyze tumor location. Results: Out of a total of 180 patients, 91 patients presented with severe MVT at baseline (50%). There was no difference in age (67 vs. 69) or sex (44% male vs. 39% male) for patients with and without MVT. The location of the tumor in the head of the pancreas was more prevalent in both groups (62% vs 53%, respectively). Out of 112 patients who completed induction, 60 presented with MVT at baseline (53%). Seventeen of these patients (28%) demonstrated partial or complete resolution of MVT during induction; most resolved MVT after the first 2 cycles of chemotherapy (15/17). Only a minority of these patients were on anticoagulation therapy (10/60, 17%). Conclusions: Severe MVT is much more prevalent in patients with LAPC than previously reported. Anticoagulation is underutilized in this cohort; however, chemotherapy may have a beneficial effect in downstaging MVT beyond anticoagulation. Clinical trial information: NCT03257033 .
Efficacy of sequential perioperative FOLFIRNOX plus gemcitabine nab-paclitaxel for resected pancreatic and periampullary cancers.
Authors: Cen Putao , Chan Kok Hoe , Wray Curtis Jackson , Thosani Nirav , Bynon John , Rowe Julie Haewon
Published: January 2023

724

Background: Perioperative chemotherapy with single regimen either FOLFIRINOX (FFX) or gemcitabine/nab-paclitaxel (Gem/NabP) is the current standard of care for pancreatic and periampullary cancers (PC) with overall survival (OS) of 2-3 years without pre-selected CA19-9 level. Sequential chemotherapy with FFX plus Gem/NabP has recently been investigated in metastatic PC and shown to improve OS. We investigated the outcome of patients who received sequential perioperative chemotherapy FFX plus Gem/NabP. Methods: Patients treated with curative intent surgery for PC who received perioperative sequential chemotherapy FFX plus Gem/NabP (each regimen was given at least two months) were identified. OS and recurrence-free survival (RFS) were calculated from the date of initial treatment (neoadjuvant chemotherapy or resection) to the date of last follow-up/death or recurrence via Kaplan-Meier analysis. Results: A total of 29 patients were identified: 24 (83%) patients had pancreatic cancer, 5 (17%) patients had periampullary cancer; 16 (55%) patients received neoadjuvant chemotherapy FFX plus Gem/NabP; 13 (45%) patients underwent upfront surgery and received adjuvant FFX plus Gem/NabP chemotherapy; 22 (76%) patients had resectable disease, the rest 7 (24%) patients had borderline or unresectable disease were all in the neoadjuvant cohort; node positivity was higher in the adjuvant cohort (n=8, 62%) than in the neoadjuvant cohort (n=8, 50%); 5 (17%) patients were found to have homologous recombination deficiency (HRD: BRCA2, CHEK, BARD, ATM) and received PARP inhibitors as part of the perioperative therapy combination. 10 (34%) patients had CA19-9 ≥ 500. Median age was 65 years (range, 45-79 years), 20 (69%) were male. During the study period, 4 (14%) patients died, and 6 (21%) patients had disease recurrence. Median RFS and OS were not reached with a median follow-up of 28 months (range, 10.9–119 months). The longest RFS was 10 years. The 2-years RFS and OS for the entire cohort was 76.7% and 88.8%, respectively. There was no statistical difference in RFS (log rank HR 1.72, 95% CI 0.23-13.15) or OS (log rank HR 0.99, 95% CI 0.20-4.93) for patients in the neoadjuvant cohort versus adjuvant cohort. Conclusions: Sequential perioperative chemotherapy combined FFX plus Gem/NabP for resected PC is effective and potentially prolongs survival, compared to historical controls who received single regimen.[Table: see text]
A pilot study for single cell RNA-sequencing of patient-derived pancreatobiliary cancer organoid.
Authors: Kim Bomi , Seo Minseok , Park Sinwoo , Park Jiho , Jin Jeonghwa , Park Jinkyeong , Lee Jong-Chan , Hwang Jin-Hyeok , Kim Jaihwan
Published: January 2023

739

Background: For precision medicine, patient-derived organoid (PDO) is regarded as one of the promising models. However, current PDOs were mainly derived from surgical specimens. We aimed to analyze the single cell RNA-sequencing (scRNA-seq) of PDO from various sampling methods with different pathologic outcomes. Methods: In 2021, three pancreatic cancer and one gallbladder cancer samples were collected from surgical specimen, endoscopic ultrasound guided-fine needle biopsy (EUS-FNB), and endoscopic retrograde cholangiopancreatography (ERCP)-guided biopsy. The samples were mechanically dissociated with dissociation buffer and incubated using shaking incubator. Dissociated cells were seeded into growth factor reduced Matrigel. From these PDOs, we generated scRNA-seq data in each experimental design, and corrected batch effects that could occur when multiple samples are considered simultaneously in downstream analysis. Marker genes representing each cell subcluster were identified, and statistical hypothesis tests were performed to identify genes differentially expressed according to differences in biopsy methods and/or pathological results. Results: We found the optimal 8 types of sub cell-type clusters with a resolution parameter of 0.3 in clustering analysis based on the Uniform Manifold Approximation and Projection (UMAP) algorithm in terms of silhouette score. As a result of examining the expression levels of KRT19, a marker gene for malignant ductal cells, and RGS5, a stellate marker gene, which showed the same pattern as the existing PDAC transcriptome studies, it was confirmed that most of the cells derived from PDOs were malignant ductal cells. Finally, we identified a heterogeneous effect on gene expression patterns in ductal cells depending on not only pathological positivity, but also biopsy methods for organoid. Conclusions: According to our scRNA-seq, most cells were malignant cells and EUS-FNB could be a good sampling method for PDOs. However, further analysis about a heterogeneous effect on gene expression patterns is necessary.[Table: see text]
KRAS WT pancreatic adenocarcinomas: Another disease?
Authors: Ben-Ammar Imen , Ducreux Michel , Boige Valérie , Hollebecque Antoine , Tarabay Anthony , Smolenschi Cristina , Gelli Maximiliano , Tanguy Marie Laure , Valery Marine , Rouleau Etienne , Barbe Rémy , Boileve Alice , Fuerea Alina Cristina
Published: January 2023

750

Background: KRAS mutation is the most common molecular alteration (MA) in pancreatic adenocarcinoma (PDAC), and only 8-10% of patients (pts) harbor KRAS wild-type tumors (WT). This study describes clinical and molecular features of KRAS WT PDAC and compares it to mutant KRAS (m KRAS) PDAC. Methods: A retrospective chart review of clinical/molecular data was performed on all pts with PDAC who had contributive molecular profile at Gustave Roussy. KRAS status was determined on tumor molecular profiling as part of routine care using an in-house panel or Foundation Medicine NGS either on tissue (63%) or liquid biopsy (37%). Results: Overall, 41 pts with KRAS WT PDAC were compared to 197 pts with mKRAS PDAC. Median OS (mOS) from initial diagnosis was significantly higher in the KRAS WT group compared to mKRAS group (32.8 months (mts), CI95% [25.9-NR] vs 21.5 mts, CI95% [18.8-24.9] respectively), as mOS from metastatic diagnosis, 26 mts, CI95% [15.7-NR] for KRAS WT pts vs 17.7 mts CI95% [15.5-19.3] for mKRAS (all p<0.05)). After adjustment on gender, age, metastasis status at diagnosis, hazard ratio (HR) of OS from metastatic stage diagnosis associated with KRAS status was 1.9 [1.1;3.4], p=0.02 (similar for 1st line PFS and OS from initial diagnosis). MA were found in 31 KRAS WT pts (76%). KRAS WT and m KRAS pts harbored different molecular profiles with less alterations of TP53, SMAD4 and CDKN2A/B (p<0.05) in KRAS WT tumors, but more of BRAF (p<0.05), PALB2, RET and BRIP1 (p=NS) alterations. Interestingly, 3 MSI tumors were found in the KRAS WT group (one received immunotherapy), vs none in m KRAS group). Tumor mutational burden was similar (2.00 Mut/Mb in KRAS WT pts vs 2.7 Mut/Mb in m KRAS pts). Based on ESCAT classification, a putative therapeutic target (ESCAT I-IV, other than KRAS) was identified in 15 (36%) KRAS WT pts and 65 (33%) m KRAS pts, thus enriching the therapeutic panel for these patients. Indeed, for example 9 (22%) KRAS WT pts received an oriented therapy after palliative treatments (such as anti-RET or anti-PARPs) and showed higher survival rates compared to KRAS WT pts who did not (mOS from diagnosis in months NR (14.2; NR) and 28.3 (26; NR) respectively). Conclusions: In our cohort of 238 PDAC, we confirm that KRAS is a prognostic factor of OS. KRAS WT PDAC have a significantly longer OS compared to m KRAS. Moreover, 36% of KRAS WT PDAC pts had a potentially actionable MA, and 9 pts displayed higher survival rates after receiving oriented therapies. This study suggests that KRAS WT PDAC should be eligible for a large molecular screening.[Table: see text]
Food insecurity and gastrointestinal (GI) cancer mortality in the United States, 2015 to 2019.
Authors: Hussaini S. M. Qasim , Chen Krista Y. , Blackford Amanda L. , Chino Fumiko , Gupta Arjun
Published: January 2023

788

Background: Food insecurity is a crucial but under-appreciated social determinant of health in GI cancers given high rates of cachexia where nutritional status may adversely impact functional status and outcomes. We investigated the impact of county-level food insecurity on age-adjusted mortality rates (AAMRs) from GI cancer. Methods: GI cancer-related deaths (ICD C15-26) were linked across US counties from 2015-2019 in the CDC WONDER database to county-level food insecurity measures from Feeding America and Census County Business Patterns databases. These included percent of individuals with food insecurity or on Supplemental Nutrition Assistance Program (SNAP) benefits, and the average cost/meal (USD) and density of local fast food/take-out restaurants. All measures were classified into quartiles based on distribution. AAMRs per 100,000 were compared between 1st and 4th quartiles for each measure using robust linear regression models with log scale and including the population size as weights. Results: There were 790,624 GI cancer deaths with overall AAMR 43.0 (68.5% age >65y, 57.8% male, 12.9% non-Hispanic Black, 8.9% Hispanic, 82.4% urban, 33.6% colorectal, 27.7% pancreatic, 19.6% liver/biliary cancer). Highest AAMRs were noted for age >65y, men, non-Hispanic White, and rural areas. AAMRs increased when moving from least to most insecure counties as defined by overall food insecurity, higher proportion of population on SNAP, or by higher local fast food density. AAMRs were lower in counties where cost per meal was higher. Association between AAMRs and all measures were strongest in younger adults (<65y), men, and rural counties, while association between AAMR and fast food density was strong among non-Hispanic Black individuals. Conclusions: Our study highlights the most food insecure US counties also have higher GI cancer mortality with significant sociodemographic variation. Food insecurity may be a helpful proxy for county-level social vulnerability in driving GI cancer mortality. Our findings recognize an important relationship between nutrition and cancer mortality and should inform ongoing congressional policy on food insecurity and assistance.[Table: see text]
Defining equitable genomic testing uptake in gastrointestinal oncology: Ensuring capture of demographic data.
Authors: Haakenstad Ellana K , Brais Lauren K. , Bertram Arrien , Kruse Andrea , Gentile Alissa , Freedman Rachel A. , Lindeman Neal Ian , Kozyreva Olga N. , Sanz-Altamira Pedro , Lathan Christopher S. , Hassett Michael J. , Cerami Ethan , Kim Annette S. , Manning Danielle , Nowak Jonathan , Giannakis Marios , Lindsley Robert Coleman , Hahn William C. , Johnson Bruce E. , McCleary Nadine Jackson
Published: January 2023

794

Background: Tumor genomic testing (GT) has increased diagnostic accuracy and treatment options for patients (pts) with cancer. Dana-Farber Cancer Institute (DFCI) has made GT accessible as an institute-supported research effort for >10 yrs. We estimate 50% standard therapies and 15-35% clinical trials in Gastrointestinal Cancer Clinic (GCC) require GT to determine eligibility. Pts in GCC with certain cancers are eligible for GT as a clinical test – these include metastatic/locally advanced colorectal, gastric, pancreatic, or biliary cancers. Clinical testing requires CLIA lab certification and insurance reimbursement; research does not. Herein we ID gaps in our GT database. Methods: We reviewed data on GT uptake in GCC between 4/2015 - 6/2022. 20,096 pts were captured by the GT tracking system. Data included: testing ordered and completed (proportion, type, time to receiving tissue for testing [TR], time to testing completion [TC]). Demographic data is not captured in the tracking system; matching unique patient identifiers with electronic health record is pending. Results: Most pts received GT (57.6%); 12% were not eligible; 30.4% declined consent. Most testing was completed (67.6%), but 21.3% of tests failed (45.5% of these from insufficient tissue). Research testing (71%) comprised most tests, but clinical tests were completed faster (median 34 days research vs 20 days clinical). Ampullary (91%), anal (90%), colon (90%) had highest completion rates; pancreatic (59%), hepatocellular carcinoma (56%) had lowest (from insufficient viable tumor in submitted specimens). Conclusions: GCC has a robust recruitment program that has yielded high GT uptake. Given the frequency that GT is used for treatment and trials, building a demographically representative dataset is crucial, especially for pts with largest burden of morbidity and mortality from cancer. We ID'd data gaps in the GT tracking system, which lacks demographics and reason for not testing. Demographic data is available in the electronic health record but does not speak with the GT tracking system so this analysis is not routinely done. Ability to visualize this data is important to ensure equitable GT uptake. Future efforts will focus on improving rates of consent in genomics databases and cancer clinical trials. Genomic testing at Dana-Farber Cancer Institute Gastrointestinal Cancer Center, 4/2015 – 6/2022.[Table: see text]
Systemic anti-cancer therapy in older patients with gastrointestinal malignancies following comprehensive geriatric assessment: An age-based subgroup analysis.
Authors: Goggin Caitriona , Walsh Darren J , Hannan Michelle , Buckley Carol , Jordan Emmet , Calvert Paula , O'Connor Miriam , Horgan Anne
Published: January 2023

796

Background: Comprehensive geriatric assessment (CGA) is recommended to inform treatment decisions in older patients with cancer. Patients ≥ 70 years are referred to the Geriatric Oncology and Liaison (GOAL) clinic in University Hospital Waterford, for a pre-treatment CGA, which includes assessment of mobility, cognitive, nutritional, functional, and psychological status, along with comprehensive geriatric pharmacological assessment. Informed treatment recommendations are made using CGA outcomes and risk assessed using the Cancer and Aging Research Group toxicity calculator. Limited information exists on treatment decisions based on age subgroups within the geriatric oncology population. Methods: Data from patients with gastrointestinal (GI) malignancies attending the GOAL clinic over a 3-year period to September 2022 were included. Patients ≥ 70 years with a G-8 (screening tool) score ≤14, and all patients aged ≥ 80 underwent CGA. An age-based subgroup analysis (< 80 vs ≥ 80) of systemic anti-cancer therapy (SACT) decisions was performed using the Chi-square test. Results: In total, 206 patients with GI malignancies were assessed, comprising 67 (33%) patients with gastroesophageal cancer, 40 (19%) with pancreaticobiliary and 92 (45%) with colorectal cancer. 40% of patients were ≥ 80 years (n = 83). The majority of patients had stage III/IV disease (82%, n = 168). Across all groups, 58% (n = 120) of patients were treated with SACT, comprising 70% of those < 80 (n = 86) and 41% (n= 34) of those ≥ 80. Across all stages (I-IV), patients ≥ 80 years were less likely to be treated with SACT compared to patients < 80 years (p < 0.01). There was no significant difference between age groups when comparing treatment intent (curative vs palliative) (p = 0.15). There was no significant difference between age groups for baseline dose reductions vs full dose (p = 0.18). Patients ≥ 80 years were less likely to receive polychemotherapy regimens in comparison with the < 80 subgroup (p < 0.01). Conclusions: Older patients with GI malignancies are a heterogeneous population. In the setting of a CGA, patients ≥ 80 years are less likely to receive SACT across any stage group, and are more likely to receive monochemotherapy regimens. The use of CGA ensures a considered and personalised approach to identify older adults most likely to benefit from active treatment and those where best supportive care alone is more appropriate.
The relationship between CT-derived sarcopenia, systemic inflammation, physical function and survival in patients with advanced cancer.
Authors: McGovern Josh , Dolan Ross D , Simmons Claribel , Laird Barry , Fallon Marie T. , Power Derek Gerard , Daly Louise , Ryan Aoife M , Horgan Paul G. , McMillan Donald C.
Published: January 2023

804

Background: The CT-derived sarcopenia score (CT-SS) is thought to capture the nutritional and functional reserve of the cancer patient. However, it is unknown whether the CT-SS is associated with measures of physical function in patients with advanced cancer. Furthermore, has complimentary prognostic value when utilised as a phenotypic criterion in the GLIM cachexia framework. Methods: Prospectively collected data from patients with advanced cancer, undergoing anti-cancer therapy with palliative intent, across nine sites in the UK and Ireland between 2011–2016, was retrospectively analysed. Relationships between the CT-SS, ECOG-PS, measures of physical function and aetiological GLIM criterion (mGPS and metastatic disease) were examined using χ2 test for linear-by-linear association. Results: 518 patients met the inclusion criteria. 55 % (n=286) were male and 51% (n=266) were 65 years of age. The majority of patients had either GI (47%, n=242) or lung (25%, n=129) tumours. 46% (n=241) were CT-SS ≥1. 53% (n=274) of patients were inflamed (mGPS≥1). 63% (n=325) had an ECOG-PS>0/1. Of the 192 patients who underwent timed up-and-go testing and two-minute walk testing, 72% (n=138) and 96% (n=185) were categorised as a failure, respectively. Median survival from entry to the study was 8.7 months (4.2-18.3). 84% (n=433), 64% (n=339) and 38% (n=194) of patients were alive at 3-, 6- and 12-months, respectively. The CT-SS was significantly associated with ECOG-PS (p<0.001), timed up-and-go test failure (p<0.05), two-minute walk test failure (p<0.05), 3-month survival (p<0.05), 6-month survival (p<0.05) and 12-month survival (p<0.05). Furthermore, was significantly associated with 3-, 6- and 12-month survival in patients who were mGPS 0 and did not have metastatic disease (p<0.05 and p<0.05, respectively). Conclusions: The CT-SS is associated with physical function and survival in patients with advanced cancer. Furthermore, has complementary prognostic value to the aetiological criterion of the GLIM framework.
Impact of early-onset colorectal cancer on utilization of chemotherapy and outcomes in patients with stage II disease.
Authors: Leary Jacob Beck , Hu Junxiao , Davis Sean , Leal Alexis Diane , Davis S. Lindsey , Kim Sunnie S. , Lentz Robert William , Friedrich Tyler , Vogel Jon , Herter Whitney , Chapman Brandon C. , Messersmith Wells A. , Lieu Christopher Hanyoung
Published: January 2023

85

Background: Rising rates of early-onset colorectal cancer (EOCRC) pose a dilemma for clinicians when deciding how to treat early-stage patients to maximize outcomes. While standard-of-care for Stage II colon cancer is largely surgical resection, evidence suggests that treatment selection may differ by patient age. We sought to determine whether rates of adjuvant chemotherapy administration differ between early and later-onset patients with Stage II CRC. Methods: Data were derived from the Flatiron National Database spanning 1/1/2003 to 8/1/2021. Patients 18 years or older with Stage II CRC were grouped into those aged 18-49 (EOCRC) and those aged 50 or older (LOCRC). Demographic characteristics, ECOG score, stage and site of tumor, and chemotherapy were included for all patients. Primary outcomes of interest included rates of adjuvant chemotherapy administration by age and ethnicity. Univariate and multivariable logistic regression models were used to evaluate relationships between chemotherapy administration, age groups, and ethnicity while adjusting for significant covariates. Results: Of 2133 patients with Stage II CRC, 1606 patients with complete data were included. A secondary analysis of 1065 patients with colon cancer was performed to address potential confounding factors related to neoadjuvant and/or adjuvant chemotherapy given in patients with stage II rectal cancer. Mean age of EOCRC patients was 45.0 years (range: 41.0-48.0) vs. 68.0 years (60.0-75.0) for LOCRC. Adjusting for ethnicity, gender, site, and ECOG score, multivariate analysis showed EOCRC patients received chemotherapy significantly more often than LOCRC patients for stage II CRC (adjusted odds ratio 1.85, 95% CI 1.32-2.60, p < 0.001). Similar findings were observed in the colon cancer only cohort (adjusted OR 2.02, 95% CI 1.31-3.09, p < 0.001). By ethnicity, non-Hispanic patients received chemotherapy at significantly lower rates than Hispanic patients in both cohorts (adjusted odds ratio 0.58, 95% CI 0.39-0.88, p = 0.009 and adjusted odds ratio 0.55, 95% CI 0.34-0.91, p = 0.018). In a subgroup analysis of Stage IIA patients, multivariate logistic regression adjusting for gender, ECOG, site, and ethnicity showed that patients with EOCRC were more likely to receive chemotherapy than patients with LOCRC (adjusted odds ratio 1.91, 95% CI 1.21-2.99, p = 0.005). Updated survival data will be presented. Conclusions: Adjuvant chemotherapy is given preferentially in Stage II EOCRC, even in Stage IIA disease, despite deviation from established guidelines. This may expose patients at low risk for recurrence to unnecessary toxicities and reveals potential provider bias in favor of younger patients in aggressively treating CRC, despite unclear evidence for any outcome benefit.
The mortality burden of cachexia in patients with colorectal or pancreatic cancer: A systematic literature review.
Authors: Dunne Richard Francis , Bonomi Philip D. , Crawford Jeffrey , Smoyer Karen E , McRae Thomas D , Rossulek Michelle I , Revkin James H , Tarasenko Lisa C
Published: January 2023

87

Background: Cancer-associated cachexia is a multifactorial wasting disorder characterized by anorexia, unintentional weight loss (WL, skeletal muscle mass with or without loss of fat mass), progressive functional impairment, and poor prognosis. This systematic literature review (SLR) examined the relationship between cachexia and survival in patients with colorectal or pancreatic cancer. Methods: The SLR was conducted following PRISMA guidelines. Embase and PubMed were searched to identify articles published in English between 1 Jan 2016 and 10 Oct 2021 reporting survival in adults with cancer and cachexia or at risk of cachexia, defined by International Consensus (IC) diagnostic criteria (Fearon et al., Lancet Oncol 2011;12:489–95) or a broader definition of any WL. Included publications were of studies in ≥100 patients with colorectal or pancreatic cancer. Results: Twenty-six publications in patients with colorectal (n=13) or pancreatic cancer (n=13) met eligibility criteria. Included studies were observational and primarily from Europe and the United States. Eleven studies (42%) reported cachexia using IC criteria and 15 studies (58%) reported any WL. An association between survival and cachexia/WL was assessed across studies using multivariate (n=23) or univariate (n=3) analyses and within each study across multiple WL categories. Cachexia/WL was associated with a statistically significantly poorer survival in at least one WL category in 16 of 23 studies that used multivariate analyses and in 1 of 3 studies (33%) that used univariate analyses. Of the 17 studies demonstrating a significant association, 9 were in patients with colorectal cancer and 8 were in patients with pancreatic cancer. Conclusions: Cachexia/WL was associated with significantly poorer survival in patients with colorectal or pancreatic cancer in nearly two-thirds of the studies. The classification of WL varied across and within studies (multiple categories were evaluated) and may have contributed to variability. Nonetheless, awareness of cachexia and routine assessment of weight change in clinical practice in patients with colorectal or pancreatic cancer could inform early disease management strategies that may improve prognosis.