bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of operative time and blood lost on overall survival after pancreaticoduodenectomy.
Authors: Kwak Hyunjee V. , Chang Amber , Peng Peter D , Kazantsev George , Spitzer Austin L , Chang CK 
Published: June 2023

e16270 Background: Blood transfusion is associated with a negative impact on cancer survival. This study aims to evaluate intra-operative time (OR time) and estimated blood loss (EBL) and their impact on survival. Methods: A retrospective review was undertaken to identify patients who had pancreaticoduodenectomy, treated at one of our 4 HPB centers of excellence for Northern California Kaiser Permanente members. All patients received their treatments between January 2015 and July 2022. The two parameters of OR time and EBL were assigned into a 2x2 grid with the creation of four separate groups. The 4 combination groups identified patients with an OR time of more than 400 minutes as time being compared and EBL of more than 600 ml as the absolute volume compared. Results: We identified 999 patients who underwent a pancreaticoduodenectomy. The mean OR time was 377 minutes, and the mean EBL was 349 ml. Portal vein resection was performed on 10.8% of patients. Neoadjuvant chemotherapy (NAT) was used in 27.8% of patients and associated with longer OR time, EBL, and portal vein resection (p<.001). Patients with OR time >400 minutes and EBL >600 ml was associated with male, higher percentage of pancreatic/bile duct cancer, portal vein resection, a longer length of stay, re-admission at 7- and 30-days post-op, neoadjuvant chemotherapy, and adjuvant chemotherapy (Table 1). Mean overall survival for the patients with an OR time >400 minutes and EBL >600 ml was 37 months, while for those with an OR time <400 minutes and EBL <600 ml was 59 months (p<.001). Conclusions: The combination of prolonged intra-operative time and blood loss is associated with decreased overall survival. The two parameters of EBL and OR time are a proxy for advanced tumors and vascular involvement gave the need for portal vein resection and higher utilization of adjuvant and neoadjuvant chemotherapy.
Disparities in pancreatic cancer among Asian-Pacific Islander and American Indian-Alaskan Native populations.
Authors: Cullen Jennifer , Rao Tharun , Dong Weichuan , Hartman Holly , Koroukian Siran 
Published: June 2023

e16275 Background: Pancreatic cancer (PanCan) is the third deadliest cancer in the United States, causing 8.2% of all U.S. cancer deaths. A steady rise in incidence rates has been observed nationally, with striking variation by geographic region and across race/ethnicity. Several studies have demonstrated a disproportionate burden of PanCan incidence on non-Hispanic Black (NHB) as compared to non-Hispanic White (NHW) populations. Yet little attention has been given to the burden of disease on Asian-Pacific Islander (API) and American Indian-Alaskan Native (AI/AN) populations. Additionally, there are limited data on disparities in PanCan incidence by U.S. geographical region. This study investigates age-adjusted incidence rates and annual percent change in PanCan incidence over a 20-year period, emphasizing burden of disease among API and AI/AN persons as well as by U.S. geographic region. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End-Results (SEER) database of 22 registries was used to study newly diagnosed pancreatic cancer cases (ICD-O-3/WHO 2008) for the period 2000-2019. Incidence rates and annual percent change were age-adjusted to the 2000 U.S. standard population and calculated per 100,000 persons using SEER*Stat software. Results: The overall age-adjusted PanCan incidence rates, from lowest to highest, for AI/AN, API, NHW and NHB populations were 6.6, 9.6, 12.5 and 15.3, respectively (per 100,000 persons). When examining each registry separately, two notable outliers were observed in the state of Hawaii where API and AI/AN persons had incidence rates of 13.4 and 24.5 per 100,000 persons, respectively. For all racial/ethnic groups, except AI/AN, the annual percent change in PanCan incidence significantly rose from 2000-2019, with increases of 0.9, 0.6 and 0.3 percent per year for NHW, API and NHB persons, respectively (p < 0.05). Conclusions: A striking observation in this study was the unusually high PanCan incidence rates among API and AI/AN persons in the state of Hawaii, as compared to national rates. Moreover, a significant increase in annual percent change in PanCan incidence was observed over the study period for all racial/ethnic groups, except AI/AN. A key strength of this analysis is the examination of a large, population-based database over an extended time period. The SEER regions examined cover approximately 48% of the U.S. population and intentionally balance on racial/ethnic composition of the U.S. However, the database does not capture cancer incidence data from all U.S. states. Furthermore, this study did not examine sub-categories of API and AI/AN persons, which are groupings that may be heterogeneous with respect to disease burden over time and across U.S. regions. Future efforts will include refining the analysis into more granular racial/ethnic groups and exploring incidence rates among API and AI/AN subgroups in Hawaii.
Genetic testing in patients with pancreatic cancer to reveal pathogenic variants in cancer susceptibility genes.
Authors: Tsoulos Nikolaos , Potska Kevisa , Agiannitopoulos Konstantinos , Tsaousis Georgios , Ozdogan Mustafa , Karabulut Bulent , Croitoru Adina-Emilia , Ziogas Dimitrios C. , Theochari Maria , Christodoulou Christos , Samantas Epaminondas , Janinis Dimitrios , Athanasiadis Ilias , Koutras Angelos , Papadopoulou Eirini , Nasioulas George 
Published: June 2023

e16276 Background: Pancreatic cancer is one of the most fatal malignancies. It accounts for 2% of all cancers and 5% of cancer-related deaths. Hence, it is essential to identify pancreatic cancer at an earlier stage to improve outcomes. A variety of hereditary cancer syndromes have been associated with an increased risk of developing pancreatic cancer, and these individuals may benefit from surveillance plans. PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring germline variant in the Homologous recombination repair (HRR) genes. Our aim was to determine the prevalence of germline pathogenic/likely pathogenic variants in cancer predisposing genes in patients with pancreatic cancer. Methods: In total, 113 patients diagnosed with pancreatic cancer were referred to our laboratory for genetic testing. The analysis of 52 genes involved in hereditary cancer predisposition was performed using a NGS approach. Results: A germline pathogenic/likely pathogenic variant was identified in 20% of patients analyzed. Among individuals with germline pathogenic/likely pathogenic variants, 60% had a positive finding in a pancreatic cancer susceptibility gene; ATM (20%), BRCA1 (20%), BRCA2 (12%), CDKN2A (4%), PALB2 (4%) while 40% carried positive findings in other cancer susceptibility genes. More specifically, in CHEK2 (16%), MRE11 (4%), RAD50 (4%), RAD51C (4%), MUTYH (8%) and NTLH1 (4%). Notably, 84% of pathogenic variants were identified in genes associated with the HRR pathway ( ATM, BRCA1, BRCA2, CHEK2, MRE11, PALB2, RAD50 and RAD51C). Conclusions: Our results indicate that multigene genetic testing is meaningful for pancreatic cancer patients as in 20% of tested individuals we identified findings associated with pancreatic or other cancer predisposition. Moreover, pathogenic/likely pathogenic variants in HRR genes, were identified in 16.6% patients and these patients might benefit from targeted treatments, such as PARP inhibitors or platinum-based treatment.
Adverse events in real-world patients covered by Medicare with metastatic pancreatic ductal adenocarcinoma who received first-line FOLFIRINOX.
Authors: Dieguez Gabriela , Tomicki Samantha , Cockrum Paul , Hirsch Jared , Bhatt Prachi , Kim George P. 
Published: June 2023

e16280 Background: FOLFIRINOX (FFX) is often associated with side effects and toxicity. This study examines real-world incidence of adverse events (AEs) and associated costs among Medicare fee-for-service (FFS) beneficiaries with metastatic pancreatic ductal adenocarcinoma (mPDAC) receiving first-line (1L) FFX. Methods: We identified patients aged 65+ with a record indicating a diagnosis of mPDAC between 2018-2021 in the Medicare Parts A, B, and D 100% Research Identifiable Files (RIF) data. Patients were required to have at least two malignant neoplasm of pancreatic duct diagnosis codes on different dates AND at least one diagnosis of a metastasis anytime on or after the first pancreatic cancer diagnosis. Patients with end-stage renal disease were excluded. Patients were assigned to cohorts based on drugs present within a 48-hour (2-day) period of a FFX chemo infusion cycle: 1) FFX with all 4 component drugs (oxaliplatin, irinotecan, leucovorin, 5-FU bolus and infusion), 2) FFX with no 5-FU bolus, but with 5-FU infusion, 3) FFX with a 5-FU bolus, but no 5-FU infusion, 4) FFX with no 5-FU of any kind and, 5) FFX with no leucovorin. Lines of therapy (LOTs) were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. Incidence rates of adverse events per administration for each cohort were determined along with the total costs of care and growth factor spending per administration. Results: We identified a total of 45,755 administrations of 1L FFX. Administrations of FFX without 5-FU of any kind (N = 842 administrations) had the lowest incidence of AEs (nausea 21.4%, neutropenia 12.5%, anemia 11.4%, fatigue 9.7%, diarrhea 10.1%, and neuropathy 5.9%), total cost of care ($6,715), and growth factor spending ($792). Administrations with all four FFX component drugs (N = 15,565 administrations) had the highest incidence of neutropenia (27.5%) and fatigue (17.5%) as well as the highest total cost of care ($7,515) and growth factor spending ($1,761). Conclusions: Among patients receiving 1L FFX, administrations with all four component drugs were associated with the highest incidence of adverse events as well as the highest total cost of care per administration cycle. In particular, neutropenia was seen in over twice as many administration cycles in patients receiving FFX with all four components (27.5%) compared to those receiving FFX with no 5-FU of any kind (12.5%). A higher incidence of neutropenia contributes to higher growth factor utilization and therefore higher costs.
Real-world treatment patterns and total cost of care in Medicare patients with metastatic pancreatic ductal adenocarcinoma who received first-line FOLFIRINOX.
Authors: Hirsch Jared , Cockrum Paul , Tomicki Samantha , Dieguez Gabriela , Bhatt Prachi , Kim George P. 
Published: June 2023

e16283 Background: Modifications to the FOLFIRINOX (FFX) regimen are used in the real world to attempt to decrease side effects and increase tolerability for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). This study assesses patterns in real-world modifications to first-line (1L) FFX and total cost of care per administration cycle in the Medicare Fee-For-Service (FFS) population. Methods: We used ICD-10 diagnosis codes to identify patients aged 65+ with mPDAC without end-stage renal disease in the 2018-2021 Medicare Parts A, B, and D 100% Research Identifiable Files (RIF) data. Study patients had 2+ claims with a pancreatic cancer diagnosis and at least one diagnosis of a metastasis anytime on or after the first pancreatic cancer diagnosis. Total cost of care (TCOC) represents mean Medicare paid amounts and patient cost sharing. Lines of therapy (LOTs) were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. Study patients were assigned to cohorts based on drugs present within a 48-hour (2-day) period of a 1L FFX chemo infusion cycle: FFX with all 4 component drugs (oxaliplatin, irinotecan, leucovorin, 5-Fluorouracil (5-FU) bolus and infusion), FFX with no 5-FU bolus but with 5-FU infusion, FFX with a 5-FU bolus but no 5-FU infusion, FFX with no 5-FU of any kind, and FFX with no leucovorin. Results: We found 45,755 administrations of 1L FFX regimens across 8,889 patients with mPDAC between 2018 and 2021. Among 1L FFX regimens, the largest cohort was comprised of administrations involving a 5-FU infusion but no 5-FU bolus (21,619 administrations, or 47%). The second largest cohort received all 4 FFX component drugs (15,565 administrations, or 34%). The other cohorts were patients receiving FFX with no leucovorin (6,300 administrations, or 14%), FFX with a 5-FU bolus but no infusion (1,425 administrations, or 3%) and patients receiving FFX with no 5-FU of any kind (842 administrations, or 2%). Administrations containing all 4 drug components had the highest cost per cycle ($7,515), and those with no 5-FU of any kind had the lowest ($6,715). Conclusions: Among Medicare beneficiaries receiving 1L FOLFIRINOX (FFX) regimens to treat mPDAC, only 34% of administrations of FFX contained all four components. Administrations most frequently omitted the 5-FU bolus. Administrations containing all 4 drug components had higher costs per cycle and those with no 5-FU of any kind had the lowest cost per cycle.
Response monitoring with ctDNA in metastatic pancreatic cancer.
Authors: Ahn Jinwoo , Hwang Jin-Hyeok , Kim Bomi , Jung Kwangrok , Kim Jaihwan , Lee Jong-chan 
Published: June 2023

e16284 Background: Various studies about clinical usefulness of serial monitoring with liquid biopsy are being conducted actively in many types of cancer. However, there is not much in pancreatic cancer. We explored whether serial ctDNA monitoring in metastatic pancreatic cancer (MPC) can be beneficial for evaluating treatment response and predicting prognosis. Methods: A total of 51 MPC patients were prospectively enrolled. Blood samples were collected at every response evaluation until progression of disease (PD) or 5th evaluation. Quantitative ctDNA were measured by droplet digital polymerase chain reaction using KRAS G12/G13 screening multiplex Kit (Bio-Rad) and reported as variant allele fraction (VAF). Percent change of ctDNA VAF (DctDNA(%) = (current VAF - previous VAF)/previous VAF*100) were correlated to radiographic responses by RECIST 1.1. Furthermore, Progression free survival (PFS) and overall survival (OS) were analyzed by DctDNA. Results: Among the 51 enrolled patients, baseline ctDNA were detected in 35 patients. During a median follow-up of 9.4 months, PD by radiographic response was observed in 24 patients. As expected, PD group showed higher DctDNA compared with non-PD group (p<0.001). DctDNA for PD yielded Area Under Curve of 0.914 (p<0.001) with 83.3% sensitivity at 90% specificity. Patients who showed early ctDNA clearance (undetectable level at first response evaluation) had longer PFS (8.1 m vs 4.7 m; HR 0.46; 95% CI 0.20 to 1.03; p=0.059) and OS (not reached vs 8.0 m; HR 0.20; 95% CI 0.06 to 0.74; p=0.009) than those who did not. In multivariable analysis, early ctDNA clearance was still associated with significantly longer PFS (HR 0.27; 95% CI 0.08 to 0.92, p=0.036) and OS (HR 0.08; 95% CI 0.02 to 0.54, p=0.007). Conclusions: Serial monitoring with ctDNA in MPC has considerable clinical potential in monitoring treatment response and predicting prognosis.
Patterns of treatment switching and healthcare resource utilization differences among real-world Medicare patients with metastatic pancreatic ductal adenocarcinoma who received first-line FOLFIRINOX.
Authors: Dieguez Gabriela , Hirsch Jared , Cockrum Paul , Bhatt Prachi , Tomicki Samantha , Kim George P. 
Published: June 2023

e16286 Background: Modifications to the FOLFIRINOX (FFX) regimen are used in the real world to attempt to decrease side effects and increase tolerability. This study assesses differences in healthcare resource utilization (HCRU) among patients who switched regimens following initial administration of first-line (1L) FFX among the Medicare fee-for-service (FFS) population with metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods: We identified patients aged 65+ with mPDAC between 2018-2021 in the Medicare Parts A, B, and D 100% Research Identifiable Files (RIF) data. Patients were required to have at least two malignant neoplasm of pancreatic duct diagnosis on different dates AND at least one diagnosis of a metastasis anytime on or after the first pancreatic cancer diagnosis. Patients were assigned to cohorts based on drugs present within a 48-hour (2-day) period of a FFX chemo infusion cycle: 1) FFX with all 4 component drugs (oxaliplatin, irinotecan, leucovorin, 5-FU bolus and infusion), 2) FFX with no 5-FU bolus, but with 5-FU infusion, 3) FFX with a 5-FU bolus, but no 5-FU infusion, 4) FFX with no 5-FU of any kind and, 5) FFX with no leucovorin. Lines of therapy (LOTs) were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. The number of patients receiving FFX and the percentage of patients who switched cohorts (e. g. had a change in the FFX drug components received) at any time during the study was identified. HCRU differences were examined for patients at 60, 120, and 180 days after the initial administration for patients who did and did not switch cohorts. Results: We identified a total of 8,889 unique patients receiving 45,755 total administrations of 1L FFX. Cohort switching was observed in 16.7% of patients. Among patients receiving FFX with all 4 component drugs in the first cycle, 19% of subsequent administrations were different. Among patients who received modified FFX regimens, switching on subsequent regimens varied (7% for FFX with no 5-FU bolus, 47% for FFX with a 5-FU bolus but with no 5-FU infusion, 18% for FFX with no 5-FU of any kind, and 5% for FFX with no leucovorin). Inpatient costs were lower and hospital outpatient and growth factor costs were higher for patients who switched cohorts vs those that did not at 60 days, 120 days, and 180 days. Conclusions: One in six patients with mPDAC receiving first-line FFX switched component drugs at least once throughout the course of their treatment. These patients had higher hospital outpatient, higher growth factor, and lower inpatient costs compared to patients who did not switch. Over time, differences in inpatient costs between the two groups were sustained, while differences in hospital outpatient and growth factor exacerbated.
Relations between mutant KRAS and TP53 subtypes and other co-mutations in pancreatic cancer.
Authors: Abraham Soniya , Zhang Janie Yue , Walther Zenta , Parekh Jay , Lacy Jill , Cecchini Michael , Hu Yiduo 
Published: June 2023

e16294 Background: The most common mutations in pancreatic cancer are found in the KRAS, TP53, CDKN2A, or SMAD4 genes. Mutations in genes involved in the DNA damage repair (DDR) pathway are also frequently seen. Despite extensive research on the patho-genomic features of pancreatic cancer, the clinical significance of these recurring mutations remains poorly understood. Methods: We identified patients with pancreatic cancer treated at Yale Cancer Center between 2016 and 2021 who underwent Oncomine tumor profiling. The incidence and subtypes of KRAS and TP53, and their association with other genomic alterations and clinicopathological variables were measured. We compared the overall survival (OS) after the diagnosis of recurrent or metastatic disease using the Kaplan-Meier method and long-rank tests. Results: One hundred fifty-nine patients were identified and KRAS mutations were seen in 144 (90.6%) patients, including 64 G12D (44.4%), 48 G12V (33.3%), 19 G12R (13.2%), 6 Q61H (4.2%), and 7 others (4.9%). TP53 mutations were identified in 117 (73.6%) patients, including 80 loss-of-function (LOF) (68.4%), 24 gain-of-function (GOF) (20.5%), and 13 variants of unclear significance (VUS) (11.1%). TP53 LOF mutations were more common in tumors with KRAS WT (40.0%), G12D (56.3%), and G12V (56.3%), than in G12R (31.6%) and others KRAS mutation (30.1%). Conversely, TP53 GOF mutations were more common in tumors with G12R (26.3%) and other KRAS mutations (23.1%), than in KRAS WT (6.7%), G12D (14.1%), and G12V (12.5%). There was no difference in OS between KRAS subtypes (p=0.48) or TP53 subtypes (p=0.52). Patients with TP53 WT had a numerically longer but not statistically significant survival (median 1.65 years versus 1.16 years in patients with TP53 mutations, p=0.20). When each KRAS subtype was examined, patients with tumors with G12V but no TP53 mutation had longer OS (median 2.42 years) than those with WT KRAS or non-G12V mutation (median 1.38 years, p=0.02). Mutations in DDR genes were more frequently seen in the KRAS WT (33.3%) and G12D groups (15.6%), compared to that in the G12V (10.4%), G12R (10.5%) groups. Unique co-mutations were observed in certain KRAS subtypes but not others. Conclusions: In this retrospective study of comprehensive genomic and clinical data of pancreatic cancers, we found that KRAS or TP53 mutation subtypes had no significant impact on OS. Different KRAS subtypes have unique co-occurring genomic alterations, which may be clinically relevant as novel KRAS inhibitors continue clinical development.[Table: see text]