bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early-onset pancreatic cancer: Defining contemporary presentation, treatment, and outcomes in the under 50 age group using real-world data.
Authors: Mendis Shehara Ramyalini , Lipton Lara Rachel , Ananda Sumitra , Michael Michael , McLachlan Sue-Anne , Thomson Benjamin N. , Knowles Brett , Fox Adrian , Nikfarjam Mehrdad , Usatoff Val , Shapiro Julia , Clarke Kate , Pattison Sharon Tracy , Chee Cheng Ean , Zielinski Rob , Wong Rachel , Gibbs Peter , Lee Belinda 
Published: January 2022

533 Background: The incidence of pancreatic cancer is increasing in younger patients (pts). Early onset pancreatic cancer (EOPC) is reportedly diagnosed at a later stage, potentially compromising outcomes compared to later onset pts (LOPC). With recent gains in staging and neo/adjuvant regimens, we sought to elaborate on the characteristics of EOPC and LOPC in a contemporary real-world cohort. Methods: The PURPLE registry, a prospectively collected multi-site data set on consecutive pancreatic cancer pts was interrogated. Patient, tumor, treatment and outcome data were extracted for EOPC vs LOPC. EOPC were those diagnosed prior to age 50 and LOPC after age 50. Resectability status was per MDT consensus. Results: Of 1534 pts, 93 (6%) were EOPC (51% male) and 1442 (94%) LOPC (51% male). EOPC had better ECOG performance status (0-1: 95% vs 81%, Relative Risk [RR] 1.2, p < 0.001) and Charlson Comorbidity Index Score (0-2: 98% vs 28%, RR 3.5, p < 0.001). Primary tumor site (head/body/tail: 66%/11%/20% for EOPC and 68%/17%/14% for LOPC), and staging (resectable/borderline resectable/locally advanced/metastatic: 29%/16%/14%/41% for EOPC vs 28%/9%/21%/41% for LOPC) did not differ. 25 (93%) of EOPC and 320 (79%) LOPC resectable pts underwent resection (p = 0.13). 12 (80%) EOPC and 36 (26%) LOPC borderline resectable pts underwent resection (RR 3.0, p < 0.001). Resection margin status (R0 vs R1 vs R2) did not differ. Resected EOPC more frequently received neoadjuvant therapy (30% vs 9%, RR 3.2, p = 0.001). EOPC were more likely to receive palliative chemotherapy in the advanced/metastatic setting (77% vs 49%, RR 1.6, p < 0.001), and were more likely to receive first line (1L) FOLFIRINOX than gemcitabine-nab-paclitaxel (36% vs 18%, RR 2, p = 0.019). Median overall survival (OS) was superior for EOPC (24 vs 12 months, Hazard Ratio [HR] 0.55, p < 0.001). For resectable pts, relapse free survival (RFS) did not differ but OS was superior for EOPC (undefined vs 27.7 months, HR 0.26, p = 0.004). In borderline resectable pts, RFS was similar and OS only numerically superior for EOPC (31.2 vs 17.7 months, p = 0.20). For locally advanced disease, 1L progression free survival (PFS1) was similar and OS was superior for EOPC (27.8 vs 11 months, HR 0.40, p = 0.008). There was no difference in PFS1/OS for metastatic pts. Conclusions: EOPC are fitter, with similar stage at diagnosis as LOPC. EOPC are more likely to receive neoadjuvant chemotherapy and undergo resection when presenting with borderline resectable disease. EOPC receive more treatment and have superior OS, with RFS/PFS1 not statistically different to LOPC.
Impact of venous thromboembolism in hospitalized patients with pancreatic cancer: A nationwide inpatient sample (NIS) study.
Authors: Thalambedu Nishanth , Ullah Waqas , Gundarlapalli Sravani 
Published: January 2022

535 Background: Pancreatic cancer (PC) has a strong association with venous thromboembolism (VTE) but the impact of it on mortality and morbidity is unknown. Inpatient costs contribute significantly to the overall cancer care costs even though there is a modest improvement in survival of pancreatic cancer patients. This study aims to determine the mortality trends and associated health care utilization in PC patients with and without VTE and to analyze its impact on hospitalized patients. Methods: We used National Inpatient Sample (NIS) to extract data for all patients above 18years of age hospitalized with a primary diagnosis of Pancreatic cancer from 2002-2018 using ICD-9 and ICD-10 codes. Unadjusted odds ratio for dichotomous outcomes were calculated, and independent t test analysis was done for continuous outcomes. Results: The odds of all-cause mortality (OR 1.35, 95% CI 1.33-1.37, p<0.001) and stroke (OR 1.82, 95% CI, 1.76-1.87, p<0.001) were significantly higher in pancreatic cancer patients with VTE compared to without VTE. PC patients with VTE were found to have significantly higher average cost of hospitalization (US $56101 vs US $46325, p<0.001) and longer length of stay(LOS) (8.20 vs 6.83, p<0.001) when compared to patients without VTE. Conclusions: Hospitalized PC patients with VTE have higher odds of mortality and stroke when compared to PC patients without VTE. Similarly, VTE in PC patients is shown to increase the hospitalization costs and overall length of stay.[Table: see text]
Predictors of early mortality in early and late onset pancreatic cancer (PC).
Authors: Kadakia Kunal C. , Trufan Sally J. , Musselwhite Laura W. , Wesson Zachary J. , Hwang Jimmy J. , Salem Mohamed E. 
Published: January 2022

543 Background: The incidence of early-onset PC (EOPC) is rising and is associated with substantial mortality. We sought to identify independent predictors of early mortality in a cohort of EOPC and matched older patients (pts). Methods: Pts with EOPC (≤50 years) and matched cohorts of average (51-69, AOPC) and late (≥70, LOPC) onset PC by sex, race, year of diagnosis, and presence of metastatic disease were identified using the institutional tumor registry for years 2011-2018. Demographic and clinicopathologic characteristics were retrieved. Overall time of survival was assessed using Kaplan-Meier curves and the Cox Proportional Hazards modeling. Multivariable regression was conducted to evaluate for predictors of early mortality in non-metastatic and metastatic pts, defined as either death within six months of diagnosis compared to those surviving at least 12 months. Results: In total, 100 pts with EOPC (median age 47, range 29-50), 100 pts with AOPC (median age 60, range 51-69), and 100 pts with LOPC (median age 78, range 70-93) were analyzed. Of these, 46% were female, 28% were black, and 43% had metastatic disease at presentation. In non-metastatic pts, the 12-mo. survival rate by age group was: EOPC 74.4% (95% CI 59-85), AOPC 60% (95% CI 43-73), and LOPC 32.4% (95% CI 18-47). Variables associated with mortality within 6 months of diagnosis in non-metastatic pts on univariable analysis included age group, BMI ≤25, ECOG performance status (PS), neutrophil-to-lymphocyte ratio ≥5 (NLR5), CA 19-9 ≥130, no surgical resection, and no adjuvant chemotherapy. Multivariable regression confirmed no surgical resection (Odds Ratio [OR] 9.6, 95% CI 3-29), no receipt of chemotherapy (OR 6.9, 95% CI 2-21), and NLR5 (OR 5.4, 95% CI 1-22) as independent predictors for early mortality in non-metastatic pts. In metastatic pts, the 12-mo. survival rate by age group was: EOPC 32.6% (95% CI 19-47), AOPC 27% (95% CI 15-41), and LOPC 5.8% (95% CI 1-16). On univariable analysis, variables associated with mortality within 6 months of diagnosis included age group, ECOG PS, and NLR5. Multivariable regression confirmed LOPC (OR 11.6, 95% CI 2-61) and NLR5 (OR 11, 95% CI 2-54) as independent variables for early mortality. Race, sex, BMI, CA 19-9, smoking, alcohol use, primary tumor location, and site of metastases were not associated with early mortality in metastatic pts. No difference in independent predictors of early mortality between EOPC and older pts were identified. Conclusions: In this cohort of EOPC and matched older pts, LOPC (age ≥70) and NLR5 were independently associated with early mortality by 6 months in metastatic pts. In non-metastatic pts, lack of curative intent surgery, no receipt of chemotherapy, and NLR5 were independently associated with early mortality. There were no independent predictors for early mortality that distinguished EOPC and older pts. Further work is needed to identify prognostic factors unique to EOPC.
Palliative care and end-of-life care in metastatic pancreatic cancer.
Authors: O'Brien Jenny , Halsey Brenton S. , Connors Meghan , Berardi Giuliana , Upadhyay Vruksha , Bauman Jessica R , Dotan Efrat 
Published: January 2022

544 Background: Patients with metastatic pancreatic cancer (mPC) have a 5-year survival of 2.7%. Studies have shown that patients with mPC receive aggressive end of life (EOL) care which has been associated with worse quality of life for patients and high use of resources when they are least likely to benefit patients. Methods: A retrospective database of patients with mPC treated at Fox Chase Cancer Center between 2010 and 2019 was analyzed for utilization of palliative care and EOL care. Statistical analysis was performed using one-sample Z tests calculated in Excel. Results: We identified 610 patients with mPC, of whom 39% received palliative care, 56% were referred to hospice, and 91.8% are deceased. The average time from mPC diagnosis to palliative care consult was 232 days, the average time from palliative care consult to death was 121 days. Patients who received palliative care were less likely to receive chemotherapy within 14 days of death (7.7% vs 13.3%, p =0.05), more likely to have a DNR code status (83.3% vs 44.5%, p < 0.0001), and more likely to be referred to hospice (83.9% vs 35.9%, p < 0.0001). The average length of time on hospice was 24 days with no difference between those who received palliative care and those who did not. Patients who were referred to hospice were also less likely to receive chemotherapy within 14 days of death (6.7% vs 19.8%, p < 0.0001). Conclusions: Patients with mPC who had a palliative care team involved in their care were significantly less likely to receive aggressive EOL care.
Clinical relevance of adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma who underwent surgery following neoadjuvant modified FOLFIRINOX.
Authors: Lee So Heun , Yoo Changhoon , Kang Sora , Chang Heung-Moon , Jeong Jae Ho , Kim Kyu-Pyo , Ryoo Baek-Yeol 
Published: January 2022

546 Background: The benefit of adjuvant chemotherapy (ACT) following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) remains unidentified. This retrospective analysis aimed to assess the clinical relevance of ACT in patients who underwent surgery following neoadjuvant mFOLFIRINOX. Methods: Between January 2017 and December 2020, 220 patients received neoadjuvant mFOLFIRINOX and underwent pancreatectomy for localized PDAC at the Asan Medical Center, Seoul, Korea. Patients unable to undergo curative-intent surgical resection (R0 or R1) and those with histological types other than ductal adenocarcinoma were excluded. Survival outcomes were compared according to ACT administration. Disease-free survival (DFS) was defined as the duration between surgery and recurrence or death of any etiology, whichever occurred first; and overall survival (OS) was that between surgery and death from any etiology. Results: ACT was administered to 150 (68.2%) patients. ACT recipients were significantly younger (median age, 61 vs. 64, p = 0.035) and they received significantly fewer cycles of neoadjuvant chemotherapy (median, 7 vs. 9, p = 0.0001) compared to non-recipients. As ACT, mFOLFIRINOX (n = 98, 65.3%), gemcitabine monotherapy (n = 39, 26.0%), and gemcitabine-capecitabine (n = 4, 2.7%) were administered. ACT recipients showed significantly better survival outcomes compared to non-recipients; median DFS 13.4 months (95% CI, 10.7–18.8) vs. 8.3 months (95% CI, 4.9–16.0), respectively (p = 0.0042); and median OS 33.4 months (95% CI, 29.9–NA) vs. 23.8 months (95% CI, 17.9–NA), respectively (p = 0.0021). DFS and OS were significantly better in ACT recipients regardless of the lymph node (LN) status during surgery (p = 0.033 for DFS and p = 0.027 for OS in negative LN; and p = 0.032 for DFS and p = 0.012 for OS in positive LN). There was no significant difference in DFS (p = 0.79) and OS (p = 0.49) between mFOLFIRINOX and gemcitabine-based regimens. In multivariate analysis, ACT remained significant as a favorable prognostic factor (DFS, hazard ratio [HR] 0.43 (95%CI, 0.26–0.71, p = 0.001); OS, HR 0.33 (95%CI, 0.17–0.64, p = 0.001). Conclusions: In PDAC patients who underwent surgery following neoadjuvant mFOLFIRINOX, ACT may be associated with improved survival outcomes. Its benefit was not affected by the LN status and ACT regimens.
A prospective phase II study of biweekly S-1, leucovorin and gemcitabine in elderly patients with locally advanced or metastatic pancreatic adenocarcinoma.
Authors: Bai Li-Yuan , Li Chung-Pin , Shan Yan-Shen , Chuang Shih-Chang , Chen Jen-Shi , Chiang Nai-Jung , Chen Yen-Yang , Tsou Hsiao-Hui , Chuang Mei-Hsing , Chiu Chang-Fang , Liu Tsang-Wu , Chen Li-Tzong 
Published: January 2022

550 Background: A chemotherapeutic regimen for elderly patients with advanced pancreatic cancer is necessary because of the considerable toxicities associated with current standard regimens. A modified combination of gemcitabine, S-1, and leucovorin (GSL) was used as a first-line treatment for elderly patients with newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma in a prospective, phase II, multicenter clinical trial (NCT03559348). Methods: Patients more than 70 years of age with ECOG performance status score 0-2 were treated with GSL. GSL was administered every 2 weeks, intravenous gemcitabine 800 mg/m2 at a fixed-dose rate of 10 mg/m2/min on day 1 and oral S-1 (80-120 mg/day) plus leucovorin 30 mg twice daily on days 1-7, until disease progression, withdrawal, or intolerable toxicities. The primary endpoint was progression-free survival (PFS). Results: Overall, 49 patients were enrolled into the trial between 10 July, 2018 and 25 March, 2020, with a median follow-up of 12.5 months. The data cut-off point was on 15 June, 2021. The median patient age at diagnosis was 76 years (range, 70–87 years), and thirty-two (65.3%) patients had metastatic lesions before GSL treatment. Patient frailty was evidenced by the Vulnerable Elders Survey (VES)-13 score (median 5, range 0-13) and Geriatric 8 (G8) score (median 10.5, range 3-15) at baseline. Among the 44 evaluable patients, 13 demonstrated a partial response (29.5%) and 24 presented with stable disease (54.5%). The median PFS was 6.6, 6.6, and 6.3 months, and OS was 12.5, 12.7, and 11.6 months for total population, patients with locally advanced disease, and patients with metastatic lesions, respectively. Patients had improved emotional function and global health status score during GSL treatment. The most frequent grade 3 or higher treatment-related toxicities included anemia (20.4%), decreased neutrophils (18.4%), decreased white blood cells (16.3%), and oral mucositis (12.2%). Conclusions: The GSL regimen results in impressive efficacy with tolerable toxicity in this group of frail patients. In addition, quality of life can be maintained during the treatment. GSL could be a treatment of choice for elderly patients with locally advanced or metastatic pancreatic cancer. Clinical trial information: NCT03559348.
Salvage ablative radiation therapy for loco-regionally recurrent pancreatic ductal adenocarcinoma following surgical resection.
Authors: Ng Victor , Zinovoy Melissa , Hajj Carla , Romesser Paul Bernard , Wu Abraham Jing-Ching , Cuaron John J , Jarnagin William R. , O'Reilly Eileen Mary , Crane Christopher H. , Reyngold Marsha 
Published: January 2022

552 Background: Dose escalated radiation therapy for localized pancreatic ductal adenocarcinoma (PDAC) is associated with improved outcomes (Reyngold, JAMA Onc, 2021). Overall survival (OS) and loco-regional failure (LRF) rates with ablative radiation therapy (A-RT) in unresectable PDAC approach those of surgery. Herein, we report outcomes of A-RT as loco-regional salvage after resection. Methods: A prospective database (2016 onward) has been maintained of all patients receiving A-RT at for PDAC. A-RT is defined as a biologically effective dose (BED) ≥96 Gy (α/β = 10). We analyzed consecutive patients from June 2016 through January 2021 who received A-RT for isolated loco-regional recurrences after resection. Survival was calculated using the Kaplan-Meier method. Results: Sixty-nine patients (40 men, 29 women) with median age of 67 received A-RT for loco-regionally recurrent PDAC. At diagnosis of recurrence, median disease-free interval from time of initial resection was 15.6 months (range 6.2–82.7) and median CA 19-9 was 65 U/mL (range < 1–1087). Twenty-one patients (30%) received neoadjuvant chemotherapy prior to surgery: pancreaticoduodenectomy (57 patients, 83%) or distal pancreatectomy (12 patients, 17%). There was a negative resection margin in 55 patients (80%). Most had T1/T2 (61 patients, 88%) and node-positive disease (44 patients, 64%). Radiation fractionation ranged from 5-25 fractions (median 25) to a total dose of 50-75 Gy (median 75). Median follow up was 16.2 months from RT. Median OS was 26.5 months from diagnosis of recurrence and 20.7 months from time of salvage A-RT. Twelve- and 24-month OS were 78.5% (95% CI 66.3–86.7) and 40.3% (25.8–54.3), respectively. In-field local failure was 8.5% (0.3–36.0) at 12 months and 27.5% (5.2–57.0) at 24 months. Respective disease-free survival at 12 and 24 months were 32.9% (21.7–44.1) and 12.3% (5.7–21.6). Grade 3 or greater gastrointestinal bleeding (GIB) occurred in 7 patients (10%), including one grade 4 event while on anticoagulation and one grade 5 event in a patient with portal hypertension. Conclusions: A-RT achieves favorable OS and LRF outcomes in patients with PDAC and an isolated loco-regional recurrence after surgical resection.
Randomized phase 2 study of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy in patients with refractory metastatic pancreatic cancer (CHECKPAC).
Authors: Chen Inna Markovna , Johansen Julia S. , Theile Susann , Hjaltelin Jessica X. , Novitski Sif I. , Brunak Søren , Hasselby Jane P. , Willemoe Gro L. , Lorentzen Torben , Madsen Kasper , Jensen Benny V. , Wilken Eva E. , Geertsen Poul F. , Behrens Claus , Nolsoe Christian , Hermann Kirstine L. , Svane Inge Marie , Nielsen Dorte 
Published: January 2022

554 Background: Pancreatic ductal adenocarcinoma remains one of the most lethal diseases. Investigating novel treatment strategies for patients with metastatic pancreatic cancer (mPC) is crucial. The purpose of this phase II trial study was to evaluate the clinical benefit of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy (SBRT) in patients with mPC. Methods: Between November 2016 and December 2019, patients with refractory mPC were randomly assigned 1:1 to SBRT of 15 Gy with nivolumab or nivolumab/ipilimumab stratified by performance status. Primary endpoint was clinical benefit rate (CBR) defined as proportion of patients with complete or partial response (PR) or stable disease, according to RECIST 1.1. Simon’s 2-stage phase II optimal design was used independently for both arms with CBR determining expansion to second stage. Secondary endpoints included safety, overall response rate, duration of response (DOR), progression free survival and overall survival (OS). Exploratory analyses included biomarkers related to immune response. Results: Eighty-four patients (41 SBRT/nivolumab and 43 SBRT/nivolumab/ipilimumab) received at least one dose of study treatment. CBR was 17.1% (95% CI, 8.0 to 30.6) for SBRT/nivolumab and 37.2% (95% CI, 24.0 to 52.1) for SBRT/nivolumab/ipilimumab. PR was observed in one patient in SBRT/nivolumab and lasted for 4.6 months. Six patients in SBRT/nivolumab/ipilimumab obtained a PR with a median DOR of 5.4 months (95% CI, 4.2 - not reached). All responders had mismatch repair proficient tumors. Grade 3 or higher treatment-related adverse events occurred in 10 (24.4%) patients in SBRT/nivolumab and in 13 (30.2%) patients in SBRT/nivolumab/ipilimumab. PD-L1 expression by tumor proportion score or combined positivity score of ≥1% was not associated with clinical benefit. On-treatment decrease in serum interleukin (IL)-6, IL-8 and CRP levels was associated with better OS. Conclusions: Clinical meaningful antitumor activity and a manageable safety profile were demonstrated after SBRT/nivolumab/ipilimumab in patients with refractory mPC. Clinical trial information: NCT02866383.
Machine learning for tracking planned versus delivered dose in pancreas SBRT.
Authors: Janopaul-Naylor James , Liu Yingzi , Lei Yang , Brackin Riley , Wang Tonghe , Yang Xiaofeng , Patel Pretesh R. 
Published: January 2022

561 Background: Cone-beam CT (CBCT) used for daily image guidance in pancreatic stereotactic body radiotherapy (SBRT) is fraught with imaging artifacts leading to poor visualization of target and avoidance structures. Machine learning methods can be used to generate synthetic CT (sCT) images from CBCT to eliminate imaging artifacts. We sought to compare planned versus delivered radiation dose to luminal GI organs at risk (OARs) during pancreas SBRT using sCT. Methods: Previously treated patients from a single institution were eligible if treated with 5 fractions of pancreas SBRT using daily CBCT and inspiration breath hold. CBCT-based sCT was generated for each treatment fraction using our previously reported cycleGAN technique. Physicians manually contoured GI OARs (stomach, duodenum, and bowel [remaining small bowel and large bowel]) on sCTs. Rigid online registration from treatment was used to re-calculate the delivered dose on each sCT. Fractional delivered dose to OARs was compared to planned dose and dose constraints with descriptive statistics. Max dose to 1cc or 20cc of an OAR was defined as D1cc and D20cc respectively. Results: 7 patients and 35 cumulative SBRT CBCT datasets were included. The median SBRT cumulative dose was 8 Gy x 5 fractions (40 Gy total). Each GI OAR was constrained per fraction to D1cc < 7 Gy (cumulative D1cc < 35 Gy) and D20cc < 4 Gy (cumulative D20cc < 20 Gy) during SBRT planning. Table shows the estimated OAR delivered doses on each sCT compared to planned doses and dose constraints. Each patient had at least 1 fraction that exceeded a planned GI OAR dose; 2 patients had delivered dose to 1cc of duodenum exceeding constraint for all 5 fractions. After a median follow-up of 9 months (range 5-34), there were 2 CTCAE Grade 1 and no Grade 2+ GI toxicity events possibly or likely related to SBRT. Conclusions: Physician contouring and dose calculation using CBCT-based sCT was feasible. Estimated delivered doses of pancreas SBRT generally exceed planned doses. Further study of sCT in pancreas SBRT is warranted for improved localization, dose calculation, and adaptive radiotherapy.[Table: see text]