bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase III study of etoposide plus cisplatin versus irinotecan plus cisplatin in advanced neuroendocrine carcinoma of the digestive system: A Japan Clinical Oncology Group study (JCOG1213).
Authors: Morizane Chigusa , Machida Nozomu , Honma Yoshitaka , Okusaka Takuji , Boku Narikazu , Kato Ken , Nomura Shogo , Hiraoka Nobuyoshi , Sekine Shigeki , Taniguchi Hirokazu , Okano Naohiro , Yamaguchi Kensei , Sato Takuji , Ikeda Masafumi , Mizuno Nobumasa , Ozaka Masato , Kataoka Tomoko , Kitagawa Yuko , Terashima Masanori , Furuse Junji ,   Japan Clinical Oncology Group（JCOG）
Published: January 2022

501 Background: Neuroendocrine carcinoma (NEC) arising in the digestive system is a rare and high-grade malignant tumor. Treatment guidelines for advanced NEC recommend platinum-based chemotherapy regimens. Etoposide plus cisplatin (EP) and irinotecan plus cisplatin (IP) are commonly used as community standard regimens for NEC. However, it is unknown which is more effective. This phase III study aimed to identify more effective regimen between EP and IP in terms of overall survival (OS) for patients with advanced NEC. Methods: Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable, histologically confirmed NEC (WHO2010) arising from the gastrointestinal tract (GI), hepatobiliary and pancreas (HBP), ECOG PS of 0-1, age of 20–75 years. In the EP arm, etoposide (100 mg/m2 on days 1, 2 and 3) and cisplatin (80 mg/m2 on day 1) were administered every 3 weeks. In the IP arm, irinotecan (60 mg/m2 on days 1, 8 and 15) and cisplatin (60 mg/m2 on day 1) were repeated every 4 weeks. The primary endpoint was OS. Total of 140 patients (114 events) were required to detect a hazard ratio (HR) of 0.67 (median OS; 8/12 months in inferior/superior arms) with a two-sided alpha of 10% and power of 70%. Due to a rapid accrual, the sample size was increased to 170 (power of 80%). Pathology was centrally reviewed after the start of treatment. Results: Of all enrolled 170 patients (GI: 100, HBP: 70) from Aug 2014 to March 2020, median OS was 12.5 months in EP and 10.9 months in IP (HR 1.043 [a ratio of EP to IP], 90% CI, 0.794-1.370, p= 0.797). Median progression-free survival (PFS) was 5.6 months in EP and 5.1 months in IP (HR 1.060, 95% CI, 0.777-1.445). Response rate (RR) was 54.5% (42/77) in EP and 52.5% (42/80) in IP among patients with target lesions. No interactions with OS, PFS, or RR were seen in pre-planned subgroup analyses including primary organs or pathological findings. The common Grade 3-4 AEs (EP/IP) was neutropenia (91.5%/53.7%), leukocytopenia (61.0%/30.5%), and febrile neutropenia (26.8%/12.2%). Conclusions: A superiority was not demonstrated, which indicates that both EP and IP remain standard first-line chemotherapy. Clinical trial information: UMIN000014795.
Long-term outcomes of rectal neuroendocrine tumors according to the risk after endoscopic resection: A multicenter study.
Authors: Lee Hyun Jin , Lee Han Hee , Kim Ilsoo , Seo Yun , Jung Hana , Oh Chang Kyo , Lee Ji Min , Choi Hyun Ho , Gweon Tae-Geun , Lee Sung Hak , Cheung Dae Young , Kim Jin Il , Park Soo-Heon 
Published: January 2022

505 Background: The detection of rectal neuroendocrine tumors has increased with advances in diagnostic endoscopy. Endoscopic resection (ER) is highly effective treatment option for small rectal neuroendocrine tumors (NETs) confined to submucosa. However, there was no risk classification for evaluating the clinical outcomes. In this study, we analyzed long-term outcomes of rectal neuroendocrine tumors after ER. Methods: In this multicenter retrospective study, we analyzed the medical records of patients who underwent ER of rectal NETs from 2009 to 2018 and were followed for ≥ 12 months at five university hospitals under the Catholic Central Medical Center in Korea. Data were collected through Catholic Medical Center Clinical Data Warehouse. We classified patients into three risk groups (low, intermediate, an high) according to clinicopathologic status of rectal NETs. The high-risk group was defined if the tumors have any of the followings: size ≥ 10mm, lymphovascular invasion, muscularis propria or deeper invasion, positive resection margins, or mitotic count ≥ 2/10. Results: A total of 346 patients were included in our study, with 144 (41.6%), 121 (35.0%), and 81 (23.4%) patients in the low-, intermediate-, and high-risk groups, respectively. Among the high-risk group, only seven patients (7/81, 8.6%) received salvage treatment at 2.1 ± 4.1 months after initial treatment. Of them, three patients underwent endoscopic submucosal dissection and the other four patients underwent surgery. There was no extracolonic metastasis in all 7 patients. During follow-up period of all included patients, although there was no local recurrence, four patients (4/346, 1.1%) had extracolonic metastasis (2 liver, 2 perirectal lymph node) at 70.5 ± 33.9 months after initial treatment. Three of them (75%) were high-risk patients without salvage treatment. The risk of extracolonic metastasis is significantly higher in the high-risk group compared with the others (P=0.041, Fisher exact test). Conclusions: Although the prognosis of the patients who underwent ER of rectal NETs showed favorable outcomes, physicians should be concerned with the possibility of metastasis during long-term follow-up of high-risk patients and consider salvage treatment.
Race, sex, age, and geographic disparities in pancreatic cancer incidence.
Authors: Moshayedi Natalie , Escobedo Anna Loraine , Thomassian Shant , Osipov Arsen , Hendifar Andrew Eugene 
Published: January 2022

520 Background: Pancreatic cancer has a poor prognosis and a 5-year survival rate of 10%. A population-risk level analysis of pancreatic cancer will identify epidemiologic risk factors including geographic, racial, ethnic, and sex inequities which could lead to improved prevention strategies. Methods: Incidence data for invasive pancreatic cancer from 2009 through 2018 was obtained from the Surveillance, Epidemiology, and End Results Research (SEER) Plus Limited-Field database (SEER 21) that covers about 37% of the US population. Age-adjusted incidence rates (AAIR) and trends were estimated by race, sex, age categories (ten-year age groups starting from age 30), and county-level rural-urban classification developed by the United States Department of Agriculture (USDA). Trends over the period are described using the annual percent change (APC) calculated using weighted least squares method. Results: Overall pancreatic cancer incidence (per 100,000 population) for all ages during 2009-2018 was 13.0. Rates were highest among Black (15.4), followed by non-Hispanic white (13.2) and Hispanic (11.6) groups in both men and women. Males carries a higher rate of incidence (14.8) than females (11.6) in pancreatic cancer although both sexes experienced a 0.6% increase in incidence yearly. Incidence of pancreatic cancer increased with age across all ethnicities in men and women. The highest rate of incidence was found in ages 80 and above (99.5) and the lowest in age group 30-39 (1.0). Pancreatic cancer rates increased by 0.6% yearly and increased in every racial/ethnic group for both males and females, except Black males (0.0) and American Indian/Alaska Native females (-0.2). Although incidence in urban counties (13.1, n = 321) and rural counties (12.8, n = 411) was comparable, rural countries observed a faster increase in rates between 2009 and 2018 (p < 0.05). Conclusions: Incidence of pancreatic cancer has increased from 2009 to 2018 across all ethnicities and in both men and women. Minorities, males, and individuals living in rural counties are disproportionately affected by pancreatic cancer. Additionally, older individuals have a higher incidence of pancreatic cancer, suggesting an increased risk in this patient population. This data will inform strategies to identify high-risk populations and implement preventative care, screening, and surveillance.[Table: see text]
Feasibility and utility of synthetic control arms derived from real-world data to support clinical development.
Authors: Lyman Jaclyn Paige , Doucette Abigail , Zheng-Lin Binbin , Cabanski Christopher R. , Maloy Molly A. , Bayless Nicholas L. , Xu Jingying , Smith William , Karakunnel Joyson Joseph , Fairchild Justin P. , Ibrahim Ramy , O'Reilly Eileen Mary , Vonderheide Robert H. , Gabriel Peter Edward 
Published: January 2022

528 Background: ‘Synthetic’ control arms (SCAs), created using electronic health records (EHRs), have immense potential to augment clinical trial findings and provide a rich context of real-world evidence (RWE) while reducing patient (pt) and sponsor burden (Gottlieb 2019). PICI0002 (PRINCE) is a ph1b/2 study evaluating APX005M with gemcitabine (gem) and nab-paclitaxel (NP) ± nivolumab for the treatment of metastatic pancreatic adenocarcinoma (mPDAC; NCT03214250). PRINCE pts were enrolled from select US academic cancer centers and a global, ph3 study was utilized for an historical reference control (Von Hoff 2013). To address the perceived limitations of this design, we explored the feasibility and utility of developing a contemporary SCA using real-world data (RWD). Methods: The SCA was derived using retrospective pt data from the two highest enrolling participating centers on PRINCE. Pts meeting key PRINCE eligibility criteria, who received gem/NP in the two years preceding the trial start date, were identified using an electronic phenotyping algorithm applied to cancer registry and EHR data, followed by manual review. Baseline characteristics, treatment exposure, efficacy and survival data were extracted electronically and via manual chart abstraction. Data were stored in a REDCap database built and housed by the Parker Institute for Cancer Immunotherapy. SCA pt characteristics were compared with PRINCE and overall survival (OS; time from initiation of gem/NP to death) was compared to historical reference controls (Table). Results: N=68 pts treated with gem/NP meeting PRINCE eligibility criteria were identified. All pts were deceased at the time of analysis. SCA pts had comparable baseline characteristics to PRINCE pts; key differences included inferior performance status and a higher proportion of pts presenting with a de novo mPDAC diagnosis. Median time on gem/NP was 4.8 months (mos; range 0-39). Median OS was 11.5 mos (95% CI 9.0-13.6) and 1-year OS was 43% (95% CI 31-55), in line with historical controls (Table). Conclusions: This study confirms the feasibility and utility of generating a control arm via a semi-automated approach. Current limitations entail manual oversight requirements as well as the known constraints of RWD, including associated biases and lack of available RECIST data. These limitations stand to evolve alongside EHR technologies. SCAs using RWD may help inform the value of prospective data by providing a contemporary reference of RWE. In some circumstances, SCAs may also serve as an alternative to traditional control arms, particularly for well-characterized standard therapies.[Table: see text]
Real-world clinical outcomes and molecular features of lung-specific and liver-specific metastases in pancreatic ductal adenocarcinoma (PDAC).
Authors: Osipov Arsen , Blais Edik Matthew , Davelaar John , Moshayedi Natalie , Nikravesh Nima , Gresham Gillian , Zheng Lei , McRee Autumn Jackson , Chuy Jennifer W. , Shroff Rachna T. , Wadlow Raymond Couric , Gregory Gary Lee , DeArbeloa Patricia , Matrisian Lynn McCormick , Petricoin Emanuel , Pishvaian Michael J. , Thomassian Shant , Gong Jun , Hendifar Andrew Eugene 
Published: January 2022

532 Background: PDAC remains one of the most lethal malignancies following metastatic presentation, typically to the liver or lung. Previous studies have observed that advanced PDAC patients have variable outcomes depending on site of involvement. Here, we aim to understand survival outcomes and molecular features for PDAC based on involvement of lung vs liver. Methods: We retrospectively analyzed longitudinal clinical outcomes across 787 patients with PDAC with next generation sequencing (NGS) from Perthera’s Real-World Evidence database whose tumors first metastasized to either the lung or the liver. Median overall survival (mOS) was measured from either the date of initial diagnosis (resectable cases only, stage I-III) or advanced diagnosis (stage IV) until death. Differences in survival and frequencies of mutations were evaluated between patients with lung-specific and liver-specific metastases using Cox regression and Fisher's exact test, respectively. Results: Among resectable PDAC, mOS from initial diagnosis was significantly shorter in patients that developed liver only metastasis (Table, left) compared to those patients that developed lung only metastasis (p=2.4e-08, HR=3.04 [2.06-4.49]). In the advanced PDAC cohort, mOS from diagnosis of advanced disease was also significantly shorter (Table, right) in liver only versus lung only metastasis (p=0.0013, HR=1.62 [1.21-2.18]). Differences in treatment-specific outcomes were not significant supporting a potential prognostic role for lung only metastases. PDAC tumors presenting to the liver first were modestly enriched (unadjusted p<0.05) for TP53 mutations (81.4% in liver vs 69.2% in lung), MYC amplifications (8.6% vs 3.0%), and inactivating CDK2NA alterations (51.5% vs 39.1%) whereas lung-specific mutation frequencies were higher for STK11 mutations (2.4% in liver vs 7.5% in lung), CCND1 amplifications (0.5% vs 3.0%), GNAS alterations (2.0% vs 8.5%). No differences in KRAS mutations nor specific isoforms were noted between lung vs liver only metastasis. Conclusions: Lung only metastasis in both resectable and advanced PDAC confers a significant survival advantage compared to liver only metastasis. Deeper investigation into the molecular drivers of site-specific metastases is warranted.[Table: see text]
A pilot study of liposomal irinotecan plus 5-FU/ LV combined with paricalcitol in patients with advanced pancreatic cancer which progressed on gemcitabine-based therapy.
Authors: Grierson Patrick , Suresh Rama , Tan Benjamin R. , Pedersen Katrina Sophia , Amin Manik A. , Park Haeseong , Trikalinos Nikolaos , Liu Jingxia , Lim Kian-Huat , wang-gillam Andrea 
Published: January 2022

566 Background: 5-FU-based chemotherapy is the standard of care for patients with advanced pancreatic cancer progressed on gemcitabine-based therapy. Based on the NAPOLI-1 study, liposomal irinotecan and 5-FU/LV is currently an FDA-approved regimen in this setting with median progression free survival (mPFS) 3.1 months, median overall survival (mOS) 6.1 months and ORR 16%. In pancreatic cancer mouse models, vitamin D was shown to remodel the desmoplastic stroma and when combined with chemotherapy significantly improved animal survival. Methods: We conducted a pilot study in patients with advanced pancreatic cancer progressed on gemcitabine-based therapy treated with 5FU (2,400mg/m2)/LV (400mg/m2)/liposomal irinotecan (70mg/m2) with paricalcitol in two dose level cohorts: paricalcitol 75mcg IV on day 1 weekly (N = 10, dose level 1) or 7mcg/kg IV on day 1 weekly (N = 10, dose level 2). The primary endpoint was the occurrence of grade 3 and 4 toxicities. Dose-limiting toxicities (DLT) were assessed during cycle 1. Secondary endpoints include objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: Between 8/29/2019 to 5/6/2021, a total of 20 patients were enrolled in the study. No DLTs or grade 4 adverse events were observed in either paricalcitol cohort. The most common toxicities were gastrointestinal (nausea, diarrhea), fatigue and anemia and were similar in both cohorts. Only one grade 3 adverse event was possibly due to paricalcitol (spinal fracture). 2/10 patients experienced an objective response, one of which was confirmed. Median follow up was 6.1 months. At the time of analysis, one patient remains on liposomal irinotecan and 5-FU/LV and mPFS of all patients is 3.57 months and mOS is 6.15 months. The mPFS is 3.55 months for dose level 1 and 5.34 months for dose level 2 (p = 0.3). The mOS is 6.15 months for dose level 1 and 6.66 months for dose level 2 (p = 0.4). Conclusions: Administration of paricalcitol in combination with liposomal irinotecan and 5-FU/LV is well tolerated in patients with advanced pancreatic cancer, however does not appear to improve response rate or survival outcomes. Correlative analyses are ongoing. Clinical trial information: NCT03883919.
Molecular precision medicine in pancreatic cancer: A single-center experience.
Authors: Tarabay Anthony , Hollebecque Antoine , Smolenschi Cristina , Antoun Leony , Klotz Caroline , Fuerea Alina , Perret Audrey , Gouriou Claire , Burtin Pascal , Belkhodja Hichem , Boige Valérie , Malka David , Ducreux Michel 
Published: January 2022

605 Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack for treatment options. Gene alterations (GAs) are frequently observed in PDAC, some of them considered as actionable with molecular targeted therapies (MTTs), with potential clinical benefits and improved outcomes. Methods: We conducted a retrospective analysis of all patients, aged ≥18 years, with histologically confirmed PDAC, who underwent tumor molecular profiling between 2010 and 2020 in our institution as part of personalized medicine trials. Overall survival was the primary study endpoint (minimal follow-up after molecular profiling, 6 months). Results: Of 115 eligible patients, molecular profiling was successful in 102 patients (89%). KRAS mutations were the most frequent GAs, mostly G12D. Actionable GAs were found in 29 patients (28%), involving mainly BRCA1/2 (5 [18%]), HER2 (5 [18%]), MTAP (5 [18%]), and FGFR (3 [11%]). Only 12 of these 29 patients (41%, or 10% of the whole population) could receive MTTs accordingly, with a median progression-free survival of 1.6 months. Median OS was 17 months in patients with actionable GAs treated with MTTs (n = 12 [11.8%]), 14 months in patients with actionable GAs not treated with MTTs (n = 17 [16.7%]), and 19 months in patients without actionable GAs treated with standard therapies (n = 73 [71.5%]; p = 0.26). The absence of liver metastases was associated with better OS (HR = 0.471, p = 0.01). The longest duration of response with MTTs was observed in patients with BRCA mutations treated with olaparib. Conclusions: Actionable GAs are found in more than the quarter of patients with advanced PDAC. Overall, targeting actionable GAs with MTTs was not associated with improved OS in this retrospective study. However, selected GA/MTT duets (e.g., BRCA mutations/olaparib) were associated with better outcome.
Disparities in place of death (PoD) in patients with gastrointestinal (GI) cancers.
Authors: Hussaini Syed , Arora Nivedita , Sedhom Ramy , Beg Muhammad Shaalan , Gupta Arjun 
Published: January 2022

645 Background: PoD is an important determinant of patient and caregiver experience. Differences in PoD may reflect disparities in care, including aggressive end-of-life (EOL) care, and access to palliative care/hospice services and caregiver support/resources. We sought to describe sociodemographic disparities in PoD in patients dying from GI cancers between 2003-2019. Methods: We used deidentified death certificate data via the CDC Wonder database. We included decedents with an underlying cause of death of GI cancer (identified through ICD codes) from 2003-2019. We stratified findings by ethnicity, race, gender, and age (< or ≥ 65 years). We classified PoD as (1) medical facility (2) nursing home, (3) home, or (4) hospice facility. We estimated Annual Percentage Change (APC) in PoD across sociodemographic groups. Results: We included 2,347,754 decedents in the analysis (43.6% women, 68.4% ≥65 years, 7.6% Hispanic, 12.7% non-Hispanic Black [NHB], 75.4% non-Hispanic White [NHW]). From 2003– 2019, across all groups, deaths in medical facility reduced from 45,046 (33.4% of all deaths in the year) to 38,673 (23.3%) (APC -2.2%), and deaths in hospice increased from 871 (0.6%) to 24,092 (14.8%) (APC 26.1%). In 2019, men more frequently died in a medical facility than women (25.5% vs. 21.1% of deaths), and women were more likely to die in a nursing home facility than men (12.6% vs. 9.8%). In 2019, individuals aged<65 years died in a medical facility more frequently than those aged ≥65 years (29.8% vs. 21.0%), and also had lower APC for medical facility deaths from 2003– 2019 (APC -1.8% vs. -2.4%). Among groups, NHWs were least likely to die in a medical facility in (21.0% of deaths in 2019) and most likely to die in a hospice facility (15.5% of deaths in 2019). Hispanic individuals (vs. non-Hispanic individuals) had higher rates of home deaths, and lower hospice and nursing home deaths. Conclusions: Despite overall reductions in deaths in medical facilities for people with GI cancers over time, there remain significant sociodemographic disparities. Targeted interventions for care access, economic stability, and social communities are needed to address these findings. PoD for patients with GI cancer.[Table: see text]