bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse events in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received FOLFIRINOX in the first line.
Authors: Kim George P. , Silver Michelle , Sanders Chad , Cockrum Paul , MacEwan Joanna P. 
Published: June 2023

e16295 Background: Quality of life is particularly important for patients (pts) with short life expectancy, such as those with metastatic pancreatic ductal adenocarcinoma (mPDAC). While first line (1L) FOLFIRINOX (FFX) is recommended by treatment guidelines for pts with mPDAC and good performance status, the regimen is known to be associated with significant toxicity that impacts quality of life. More than half of pts experience adverse (AEs)—such as nausea and vomiting, diarrhea, fatigue, neuropathy, anemia, thrombocytopenia, and neutropenia—during treatment with FFX. Efforts to reduce AEs have led to the use of modified FFX (mFFX) regimens that utilize lower doses of components of the regimen. Additional evidence on AEs associated with FFX and mFFX in the real world (RW) is needed. We assessed AEs in a RW cohort of mPDAC pts treated with FFX or mFFX in 1L. Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between January 2015 and November 2022 who initiated treatment with FFX or mFFX within 90 days of their diagnosis for metastatic disease (1L) were included in the study. Pts were required to have an available body surface area measurement within 7 days of the index date. mFFX was defined as administration of (i) < 150mg/m2 of irinotecan, or (ii) < 2,720mg/m2 5-FU total during cycle 1. Diarrhea, fatigue, nausea and vomiting, and neuropathy were available in the data as ungraded AEs abstracted from clinician notes. Assessment of hematologic and hepatic AEs were based on observed lab values and were graded according to the Common Terminology Criteria for Adverse Events version 5. Results: Of the 1,326 pts meeting study inclusion criteria and receiving 1L treatment with FFX or mFFX, 1,325 received mFFX and 1 received FFX. The median age at 1L initiation was 65yr (IQR: 58–70), 57% (754 pts) were male, 69% (916 pts) were white, 15% (197 pts) had an ECOG score of 0, 42% (550 pts) had an ECOG score of 1, and 78% (1028 pts) were stage IV at diagnosis. The median number of cycles was 5 (IQR: 3–10) and the median dose intensity per week was 940 mg/m2 for 5-FU, 179 mg/m2 for leucovorin, 38 mg/m2 for oxaliplatin, and 73 mg/m2 for irinotecan. Notable grade 3/4 AEs were: 16.4% neutropenia, 4.4% thrombocytopenia, 5.7% anemia, 4.7% elevated ALT, 4.9% elevated AST, and 10.6% elevated ALP. Of the ungraded AEs reported in clinician notes, 17.3% of pts experienced diarrhea, 10.9% fatigue, 10.9% nausea and vomiting, and 11.9% neuropathy. Conclusions: In a RW cohort of mPDAC pts treated with 1L FFX or mFFX, nearly all were treated with mFFX. The burden of serious AEs for mPDAC pts during 1L treatment with FFX or mFFX was high, with 30% (403 pts) experiencing at least one grade 3/4 AE.
Incidence of palliative care consultations in end-of-life care among patients with pancreatic cancer in the US.
Authors: Gokul Kaushik , Zhang Zidong , Subramaniam Divya S. 
Published: June 2023

e16302 Background: Integration of palliative care in the treatment plan for a variety of diseases has been shown to improve quality of life, reduce aggressive interventions, and reduce cost burdens. This study aimed to explore the incidence of palliative care consultations in pancreatic cancer patients and determine its influence on the utilizations of aggressive interventions towards end of life. Methods: We conducted a retrospective study using a de-identified national Electronic Health Record (EHR) database, which captured deceased patients between January 1, 2000 to December 21, 2018, with a diagnosis of pancreatic cancer. Clinical history from 0-6 months prior to death was examined for the presence of a palliative care consultation (PCC) encounter. Aggressive interventions of interest, namely emergency department visits, chemotherapy, and ICU admissions, were identified and recorded in both the last six months and the last month of life. Demographic variables such as age, gender, race, and location were also considered during analysis. The PCC group and non-PCC group were compared using the Whitney U-test and Chi-squared test. Results: 2,883 deceased patients with PanCa were identified. However, 2,025 of these patients did not receive PCC in the last six months of life. The average age of death was greater at 70.5 years within the PCC group as compared to 68.9 years within the non-PCC group. This difference was statistically significant. In the last 6 months prior to death, 14.1% of patients overall had chemotherapy. The proportion of patients having chemotherapy was greater among the PCC patients compared to those not (22.4% vs 10.6%). Compared to those who did not receive PCC, patients who had PCC in the end of life were also more likely to be hospitalized (81.1% vs 38.2%), visit emergency departments (45.1% vs 23.7%) and stay in the ICU (14.1% vs 4.0%). In the last 30 days of life, trends were similar. Within PCC, 3.4% had chemotherapy while 1.3% had chemotherapy in the non-PCC group. As far as hospitalizations go, among patients with PCC, 51.3% were hospitalized compared to 15.5% hospitalizations in non-PCC. In patients who had PCC, 14.8% had at least one emergency department visit while 4.8% of patients in the non-PCC group had at least one emergency department visit. Lastly, ICU stays showed a similar trend to the previous interventions. In PCC patients, 7.9% had at least one ICU stay while only 1.5% of patients had one in the non-PCC group. Conclusions: Our study found that less than 30% of patients with PanCa received PCC at the end of life. Findings show an urgency to increase awareness and utilization of PCC for such patients. Interventions should be developed to address this urgency to help improve quality and efficiency of care. Future studies will also identify barriers and facilitators in implementing PC and consultation for patients with PanCa.
Differences in outcomes of patients with advanced neuroendocrine tumors treated with chemotherapy versus targeted agents.
Authors: Freeman Jesica , Stacey Jennifer 
Published: June 2023

e16303 Background: Pancreas NETs are uncommon and very rare cancer accounting for around 7% of the pancreatic cancer sub patient population, 4,200 patients in the US diagnoses yearly of all cancers in the pancreas. There are very few treatment options available for Metastatic Pancreatic Neuroendocrine Tumor patients. The survival rate depends on a variety of factors, including whether the tumor can be removed using surgery and if the cancer has spread to other parts of the body. The 5-year survival rate non-metastatic pancreas NETs is 93% while metastatic pancreas NETs is 24%. Therefore, this study compares the 5-year overall survival rate of metastatic pancreatic NETs ineligible for surgery who have received chemotherapy alone versus who have received targeted therapy. Methods: Patient cohorts were generated in an electronic medical records (EMR) TriNetX Research Network of 89M patient lives. Patients were identified as either receiving a targeted therapy or patients who were targeted therapy naïve receiving chemotherapy. Both cohorts had a diagnosis of pancreatic NETs (ICD-10 C25.4), at least one documentation of a related metastasis, and no history of any pancreatic surgery. The 5 year overall survival (OS) from first exposure to either targeted therapy or chemotherapy was analyzed using measures of association and survival analysis conducted via Kaplan-Meier estimator. Cohort comparisons were with propensity score matching (PSM) to control for demographic, comorbidity, medication, and diagnostic procedure confounders. Results: After matching, each cohort accounted for 389 patients (43% female, mean age at index 62 +/- 13 SD). There was a significant 5-year mortality risk difference (11.054%, p = 0.0020) between the chemotherapy only cohort (215 patients, 55.27%) vs. the targeted therapy cohort (172 patients, 44.216%) after adjusting for potential confounding factors. Additionally, the 5-year OS rate was 24.951% in the chemotherapy only cohort and 37.222% in the targeted therapy cohort. The difference in survival between the groups was statistically significant (log-rank p = 0.0001). Conclusions: In these cohorts of patients with metastatic pancreas NETs without surgical treatment, we found that targeted therapy was associated with a significant improvement in 5-year overall survival compared to standard chemotherapy alone. Our results suggest that targeted therapy should be considered as a first line treatment option for this severe patient population.
Description of technique for endoscopic ultrasound-guided tissue acquisition in pancreatic cancer for comprehensive molecular profiling: Results of a randomized trial.
Authors: Bang Ji Young , Jhala Nirag , Seth Anjali , Krall Konrad , Navaneethan Udayakumar , Hawes Robert , Wilcox C. Mel , Varadarajulu Shyam 
Published: June 2023

e16306 Background: As theoretically actionable genomic lesions are found in almost 50% of pancreatic cancers which can impact clinical management in up to 30% of patients, there is increased focus on molecular profiling. Although EUS-FNB is an established method for achieving pathological diagnosis in pancreatic cancers, the technique of tissue acquisition for comprehensive molecular profiling (CMP) has not been described. Methods: Patients proven to have pancreatic adenocarcinoma using rapid onsite evaluation (ROSE) at EUS were randomized to undergo two or three dedicated FNB passes for CMP. Tissue was procured using 22G Franseen needle adopting the fanning technique and stylet-retraction maneuver. Genomic DNA and total RNA were extracted from formalin-fixed paraffin-embedded (FFPE) cell blocks (Qiagen AllPrep). Next-generation sequencing (NGS) was performed (Archer Panels) for analyzing 69 gene DNA mutations (single nucleotide variants, insertions, and deletions) and 53 RNA somatic oncogenic gene fusions. Main outcome measure was the proportion of specimens in which adequate DNA and RNA were extracted for CMP. Results: 33 patients (mean age 77.0 years [SD 7.7], female = 20) with pancreatic cancer (location = head/uncinate 22; other 11) were randomized to two (n = 17) or three (n = 16) FNB passes. While sufficient DNA was extracted from all 33 FFPE cell blocks, adequate RNA was extracted from 15 of 16 in the three pass (93.8%) vs. 16 of 17 in the two pass cohort (94.1%) (p = 0.99). There was no significant difference in the mean concentration of DNA (two passes 10.7 ng/ul [SD 7.1] vs. three passes 7.9 ng/ul [SD 4.4]; p = 0.19) or RNA (two passes 37.1 ng/ul [SD 26.5] vs. three passes 28.9 ng/ul [SD 13.2]; p = 0.29) between the groups. While somatic oncogene RNA fusion (LDAH-ETV1) predictive of metastatic disease was identified in one specimen, DNA mutations were identified in all 33 specimens that included one BRCA1 mutation that warranted Oxaliplatin-based chemotherapy. Conclusions: Specimens of adequate quantity and of high quality for comprehensive molecular profiling in pancreatic cancer can be procured in nearly 95% of patients by performing two dedicated passes using the 22G Franseen needle, adopting the fanning maneuver and stylet-retraction technique. Clinical trial information: NCT05043532 .
Comprehensive genomic landscape in pancreatic cancer using whole-exome sequencing.
Authors: He Yonggang , Huang Xiaobing , Zheng Lu , Huang Wen , Tang Yichen , Peng Xuehui , Li Jing , Wu Jing , You Nan , Liu Chuang , Zhang Yaxuan , Li Ling 
Published: June 2023

e16307 Background: Pancreatic ductal adenocarcinoma is one of the fatal malignancies in the world, mostly as a result of the absence of early detection and specific treatment solutions. Consequently, identifying mutational profiles and molecular biomarker are essential for increasing the viability of precision therapy for pancreatic cancer. Methods: We gathered blood and tumour tissue samples from 47 Chinese pancreatic cancer patients and used whole-exome sequencing (WES) to evaluate the genetic landscape. Results: Our results showed the most frequently somatic alteration genes were KRAS (74.5%), TP53 (51.1%), SMAD4 (17%), ARID1A (12.8%), CDKN2A (12.8%), TENM4 (10.6%), TTN (8.5%), RNF43 (8.5%), FLG (8.5%) and GAS6 (6.4%) in Chinese pancreatic ductal adenocarcinoma patients. We also found that three deleterious germline mutations ( ATM c.4852C > T/p. R1618*, WRN c.1105C > T/p. R369*, PALB2 c.2760dupA/p. Q921Tfs*7) and two novel fusions ( BRCA1-RPRML, MIR943 (intergenic)- FGFR3). When compared to the Cancer Genome Atlas (TCGA) database, there is a greater mutation frequency of TENM4 (10.6% vs. 1.6%, p= 0.01), GAS6 (6.4% vs. 0.5%, p= 0.035), MMP17 (6.4% vs. 0.5%, p= 0.035), ITM2B (6.4% vs. 0.5%, p= 0.035) and USP7 (6.4% vs. 0.5%, p= 0.035) as well as a reduced mutation frequency of SMAD4 (17.0% vs. 31.5%, p= 0.075) and CDKN2A (12.8% vs. 47.3%, p< 0.001) were observed in the Chinese cohort. Among the 41 individual examined for PD-L1 expression, 15 (36.6%) had positive PD-L1 expression. The median tumour mutational burden (TMB) was found to be 12 muts (range, 0-124). The TMB index was higher in patients with mutant-type KRAS MUT/ TP53 MUT ( p< 0.001), CDKN2A ( p= 0.547), or SMAD4 ( p= 0.064) compared to patients with wild-type KRAS/ TP53, CDKN2A, or SMAD4. Conclusions: We exhibited real-world genetic traits and new alterations in Chinese individuals with cancer of pancreas, which might have interesting implications for future individualized therapy and medication development.
Efficacy of adjuvant chemoradiotherapy in patients with pancreatic ductal adenocarcinoma after surgery: A real-world study in high-volume pancreatic cancer center.
Authors: Wu Lili , Guo Xi , Xu Yaolin , Wang Dansong , Wu Wenchuan , Kuang Tiantao , Xu Xuefeng , Liu Liang , Wang Wenquan , Du Shisuo , Zhou Yuhong , Lou Wenhui 
Published: June 2023

e16308 Background: Whether adjuvant chemoradiotherapy provides survival benefit for pancreatic ductal adenocarcinoma (PDAC) patients remains unknown. Methods: This prospective real-world study recruited PDAC patients receiving surgical treatment in Zhongshan Hospital Fudan University, Shanghai, China from June 2020 to December 2021. Patients with carcinoma in situ, distant metastases, synchronous cancers within 5 years, and receiving neoadjuvant therapy were excluded. Patients were then categorized into three groups according to their adjuvant treatment: C- (without adjuvant chemotherapy), C+R- (with adjuvant chemotherapy only), and C+R+ (with adjuvant chemoradiotherapy). Overall survival (OS) and disease free survival (DFS) were compared between groups. Results: A total of 216 patients were included in the final analyses. Median follow time for three groups ranged from 18 to 21.9 months. OS and DFS were significantly different between groups (OS, p value = 0.0088; DFS, p value = 0.0037). Median OS (mOS) for C- and C+R- were 24.3 (95% confidence interval [CI], 18 - not available [NA]) and 29.5 (24.9 – NA). Patients in C+R+ groups did not reach mOS (27.2 - NA). Median DFS (mDFS) for C-, C+R-, and C+R+ were 8.42 (5.72 - NA), 16.9 (13.91 - NA) and 19.66 (16.83 - NA), respectively. Conclusions: Adjuvant treatment significantly increased survival outcomes of pancreatic cancer patients after surgical treatment. In order to find out whom might benefit from additional radiotherapy and which is the best therapy combination, more detail information, including chemotherapy regimen, staging, resection margin, etc., were needed to include in the survival analyses. Clinical trial information: NCT04737551 . [Table: see text]
Evaluating adherence to NCCN guideline-directed genetic screening for patients with pancreatic ductal cell adenocarcinoma in rural northeast Georgia.
Authors: Ghosh Aditya Kumar , Bhushan Sheena , Abidoye Oluseyi , Sampat Devi 
Published: June 2023

e16311 Background: Patients with mutations in BRCA 1/2 genes are at increased risk for pancreatic ductal cell adenocarcinoma (PDAC) in addition to breast and ovarian cancer. In 2019, the NCCN updated its guidelines recommending gene testing for all patients with PDAC to include associated genes: ATM, BRCA1, BRCA2, CDKN2A, MSH2, MLH1, MSH6, EPCAM, PALB2, STK11, TP53. This retrospective, observational study reports on adherence to genetic screening recommendations among patients with newly diagnosed PDAC who received oncologic care in rural Northeast Georgia (NEGA). Methods: Chart abstraction was performed utilizing the EPIC database from hospital electronic medical records of patients who were diagnosed with PDAC between 1/1/20-12/31/21 and received oncologic care in rural NE GA. This abstraction was completed to include information on gene testing recommendations, testing completion, and time from diagnosis to testing. The deidentified dataset was then analyzed using appropriate descriptive and associative statistical testing. Results: Of the cohort of 109 patients diagnosed with PDAC over these two years, only 32 (29.4%) received recommendations and completed genetic screening. Among this segment of patients, 16 (14.7%) were screened within 10 days of diagnosis, 8 (7.3%) within 11-30 days, and 6 (5.5%) were screened over 30 days after being diagnosed with PDAC. Among the 77 (70.6%) patients who did not receive screening, 45 of them (41.3%) did not receive any discussion regarding screening despite planning for other standard of care treatment. The remaining 32 patients (29.4% of the no screening cohort) did not receive screening due to desire to pursue palliative care/hospice/or due to terminal illness that prevented further workup. Of the 45 patients who did not receive screening despite PDAC treatment intent, majority (43; 95.5%) did not receive recommendations regarding the importance of genetic screening. Gene testing of the 32 patients who had screening completed showed that 4 (12.5%) had a pathogenic mutation (3 with CFTR; 1 ATM) and 16 (50%) had variants of unknown significance (VUS). Conclusions: This study highlights a gap in adherence to guideline-directed genetic testing in PDAC patients. Notable findings include increased likelihood to complete the test when recommendations and discussions of genetic screening occurred early in the course after initial diagnosis of PDAC. Moreover, 12.5% of those screened were found to have pathogenic mutation and half were found to have at least one VUS suggesting that genetic screening may potentially identify causative mutations. The findings also highlight the consideration for gene testing recommendation for the large proportion of patients who are terminally ill at diagnosis, as genetic screening would potentially benefit the family members and inform that they receive genetic screening as well.
Risk stratification of pancreatic ductal adenocarcinoma patients undergoing curative-intent surgery after neoadjuvant therapy.
Authors: Yang Hyun Kyung , Park Mi-Suk , Han Kyunghwa , Eom Geonsik 
Published: June 2023

e16312 Background: To identify preoperative factors associated with survival in pancreatic ductal adenocarcinoma (PDAC) patients who underwent curative-intent surgery after neoadjuvant therapy (NAT) and develop risk stratification criteria. Methods: Consecutive PDAC patients who underwent post-NAT curative-intent surgeries between 2007 and 2020 at a high-volume center were retrospectively analyzed. Demographic, laboratory, surgical, and histopathologic variables were collected. Baseline, preoperative, and interval changes of CT findings proposed by the Society of Abdominal Radiology and the American Pancreatic Association were analyzed. Cox proportional hazard analyses were used to identify preoperative variables associated with survival since the time of diagnosis. We developed risk stratification criteria using the variables independently associated with survival, i.e., "post-NAT response criteria." We compared the discrimination performance of "post-NAT response criteria" with that of post-NAT pathological (yp) AJCC TNM staging system. Results: A total 145 PDAC patients who completed chemo- (n=47) or chemoradiation therapy (n=98) were included. Stable or increased tumor size on CT (hazard ratio, 2.58 [1.58, 4.21]; P < 0.001) and elevated preop. CA 19-9 level (1.98 [1.11, 3.55]; P = 0.021) were independent poor prognostic factors. The survival of the patient groups stratified by "post-NAT response criteria" which combined changes in tumor size and CA 19-9 showed significant difference (P < 0.001). Such stratification was comparable to ypTNM staging in discrimination performance (difference of C-index, 0.068 [-0.012, 0.142]). Conclusions: Decrease in tumor size and CA 19-9 normalization or staying normal until the time of surgery were independent favorable factors of survival. The combination of the two factors discriminated survival comparably to ypTNM staging.[Table: see text]
Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomized clinical trial.
Authors: Issels Rolf D. ,   for the European Society of Hyperthermia Oncology (ESHO) and the German Arbeitsgemeinschaft Internistische Onkologie (AIO) Study Group for Pancreatic Cancer
Published: June 2023

e16316 Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adeno- carcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma. Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m2 on day 1, 15 and cisplatin 25 mg/m2 with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m2 on day 1,8,15), four-weekly over six cycles. Disease- free survival (DFS) was the primary end-point. Secondary end-points included overall survival (OS) and safety. Results: A total of 117 eligible patients (median age, 63 years) were randomly allocated to treatment (57 GPH; 60 G). With a follow-up time of 56.6 months, the median DFS was 12.7 compared to 11.2 months for GPH and G, respectively (p= 0.39). Median post- recurrence survival was significantly prolonged in the GPH-group (15.3 versus 9.8 months; p= 0.031). Median OS reached 33.2 versus 25.2 months (p= 0.099) with 5-year survival rates of 28.4% versus 18.7%. Excluding eight patients who received additional capecitabine in the G- arm (investigators choice), median OS favored GPH (p= 0.052). Adverse events CTCAE (Common Terminology Criteria for Adverse Events) grade >=3 occurred in 61.5% (GPH) versus 63.6% (G) of patients. Two patients in the G-group died because of treatment- related toxic effects. Conclusions: The randomised controlled Hyperthermia European Adjuvant Trial study failed to demonstrate a significant difference in DFS. However, it showed a difference in post- recurrence survival and a strong trend for improved OS. Regional hyperthermia (RHT) with cisplatin offers innovative treatment options in PDAC. Clinical trial information: NCT01077427 .