bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world eligibility of advanced pancreatic (APC) patients for maintenance olaparib.
Authors: Batra Atul , Cheung Winson Y. , Tang Patricia A. 
Published: February 2020

653 Background: The POLO trial demonstrated an improvement in progression free survival (PFS, 7.4 months vs. 3.8 months; hazard ratio, HR, 0.53; 95% confidence interval, 95% CI, 0.35 to 0.82; P=0.004) with olaparib compared to placebo, as maintenance therapy in APC patients with germline BRCA 1/2 mutations with disease control after 16 weeks (DC16) of platinum-based first-line therapy. This study aims to identify the proportion of real-world APC patients eligible for olaparib, and to determine the PFS and overall survival (OS) after DC16. Methods: APC patients treated with first-line FFX in Alberta were identified (2011-2018). We conducted an analysis of baseline characteristics to identify factors associated with DC16. Results: We identified 165 APC patients treated with FFX with unknown BRCA 1/2 status, of which 56% were males and median age at diagnosis was 59 years (interquartile range 38-75 years). Of these, 72 (44%) had DC16. Normal LDH and ALP, and albumin more than 35 g/L were associated with a higher likelihood of having DC16 (table). The PFS of patients with DC16 was significantly higher than those with DC<16 weeks (9.3 vs 2.5 months, HR=0.22, 95% CI 0.15-0.32, P<0.001). In patients who had DC16, median PFS and OS from that point were 5.6 months and 17.9 months, respectively. Conclusions: Less than half of real-world patients treated with first-line FFX would be eligible for olaparib by the criteria of DC16 with FFX. Median PFS after DC16 is 5.6 months with FFX in patients with unknown BRCA 1/2 status. This provides a baseline for future trials evaluating maintenance strategies. Patients with APC and higher disease burden (higher ALP and LDH) and low albumin are less likely to have DC16. [Table: see text]
Gemcitabine and nab-paclitaxel in older adults with metastatic pancreatic cancer: Are two doses per cycle enough?
Authors: Winer Arthur , Handorf Elizabeth A. , Dotan Efrat 
Published: February 2020

655 Background: The dosing of Gemcitabine and Nab-Paclitaxel (GA), a frontline regimen to treat metastatic pancreatic cancer (mPC), is frequently altered from the traditional dosing schedule (TDS) of day 1, 8, and 15 of a 28 day cycle to a modified dosing schedule (MDS) of 2 doses/cycle. Previous work showed that overall survival (OS) was similar between patients (pts) treated with the MDS vs the TDS. We sought to analyze a larger real-world database to assess these trends. Methods: We retrospectively analyzed de-identified pts with mPC ≥ 65 y/o treated with GA in the Flatiron Health nationwide EHR-derived database. Demographics, treatments (tx), and outcomes were collected. Pts were grouped as either starting with the TDS or MDS. Analysis included time on treatment (TOT) as well as OS. A Cox model was used to test non-inferiority of the MDS vs the TDS for both TOT and OS, adjusting performance status, age, race, gender, and line of therapy (LOT). The upper bound for non-inferiority was a Hazard Ratio (HR) = 1.2. Results: 1497 pts were treated between 1/1/14-5/31/19; 883 pts with the TDS and 614 with the MDS. Median TDS age was 72 (65-85) and MDS was 73 (65-84) (p<0.001). 1237 pts received first- line GA; 60% received the TDS, 40% the MDS. The use of the TDS vs MDS did not vary significantly by LOT, gender, or race, but more pts with a PS of ≥2 received the MDS (p=0.03). In the first-line, outcomes were better for the TDS vs the MDS (unadjusted median TOT 5.3 vs 3.2 mo, p<0.001, OS 9.2 vs 5.3 mo; p<0.001), with consistent results in the ≥ second-line. The MDS did not meet its non-inferiority boundary: first-line TOT HR=1.4 [95% CI 1.2-1.6]; second+ line TOT HR=1.3 [95% CI 1.0-1.7]; first-line OS HR=1.6 [95% CI 1.4-1.8]; second+ line OS HR=1.3 [95% CI 1.0-1.8]. Results were consistent when additionally stratified by PS 0-1 vs 2+. Conclusions: In this large real-world cohort, first-line GA tx with a MDS did not meet criteria for non-inferiority for TOT and OS vs a TDS in older adults with mPC. With the caveats of potential confounding that exist in a de-identified retrospective database, these results suggest that dose intensity may be important in pts with mPC. Further prospective studies are necessary to ensure we utilize effective tx strategies in older adults with mPC.
Blood-based detection of early-stage colorectal cancer using multiomics and machine learning.
Authors: Putcha Girish , Liu Tzu-Yu , Ariazi Eric , Bertin Marvin , Drake Adam , Dzamba Michael , Hogan Greg , Kothen-Hill Steven , Liao Jeffrey , Li Kang , Mahajan Shivani , Palaniappan Krishnan , Sansanwal Poonam , St John John , Ulz Peter , Wan Nathan , Warsinske Hayley , Weinberg David , Yang Rui , Lin Jimmy 
Published: February 2020

66 Background: Despite population screening efforts, screening rates for colorectal cancer (CRC) remain suboptimal. A non-invasive, blood-based screening test with high sensitivity and specificity in early-stage disease should improve adherence and ultimately reduce mortality; however, tests based only on tumor-derived biomarkers have limited sensitivity. Here we used a multiomic, machine learning platform to discover, refine, and combine tumor- and immune-derived signals to develop a blood test for the detection of early-stage CRC. Methods: Samples from 591 participants enrolled in a prospective study including average-risk screening and case-control cohorts (NCT03688906) were included in this analysis (CRC: n = 43; colonoscopy-confirmed CRC-negative controls: n = 548). Participants with CRC were 60% male with a mean age of 63, and controls were 55% male with a mean age of 60. Stage distribution was 54% early (I/II) and 34% late (III/IV) with 11% unknown. Plasma was analyzed by whole-genome sequencing, bisulfite sequencing, and protein quantification methods. Computational methods were used to assess and infer the performance of individual and combined assays. Results: For colorectal adenocarcinoma, which represents ~95% of all CRCs, our multiomic test achieved a mean sensitivity of 92% in early stage (n = 17) and 84% in late stage (n = 11) at a specificity of 90%. Across all CRC pathological subtypes, our test achieved a mean sensitivity of 80% in early stage (n = 19) and 83% in late stage (n = 12) at a specificity of 90%; the test detected the single squamous cell carcinoma but missed both neuroendocrine tumors. Individual assays achieved a mean sensitivity of 50% in early stage and 66% in late stage at a specificity of 90%. Conclusions: In a prospective cohort, we demonstrated high sensitivity and specificity for early-stage adenocarcinoma by combining tumor- and immune-derived signals from cfDNA, epigenetic, and protein biomarkers. While most CRCs are adenocarcinomas, detection of all pathological subtypes is required to maximize sensitivity in a screening population. Further analysis of molecular and pathological subtypes, as well as the entire ~3000 patient cohort, is underway. Clinical trial information: NCT03688906.
Observational retrospective evaluation of treatment with liposomal irinotecan plus fluorouracil/leucovorin for metastatic pancreatic cancer patients: An Italian large real-world analysis.
Authors: Pellino Antonio , Manai Chiara , Merz Valeria , Scartozzi Mario , Milella Michele , De Vita Ferdinando , Antonuzzo Lorenzo , Zichi Clizia , Satolli Maria Antonietta , Panebianco Michele , Noventa Silvia , Giordano Guido , Nappo Floriana , Zecchetto Camilla , Puzzoni Marco , Vaccaro Vanja , Pappalardo Annalisa , Giommoni Elisa , Melisi Davide , Lonardi Sara 
Published: February 2020

660 Background: In the NAPOLI I phase III trial, Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) showed better outcome compared to 5FU/LV in patients with metastatic Pancreatic Cancer (MPC) progressed to 1st- line gemcitabine-based therapy. Aim of this study is to explore the real-world efficacy and safety of 5FU/LV-nal-IRI by a compassionate use programme and to identify potential prognostic factors that could affect survival in this setting. Methods: This is a retrospective multi-center analysis including patients with MPC who received 5FU/LV-nal-IRI after failure of a gemcitabine-based therapy. Survival analyses were carried out by the Kaplan-Meier method. Univariate and multivariate analyses were performed by using the log-rank test and the Cox regression. Results: A total of 296 pts (median age, 69 years, range 30-82; 50% male; ECOG PS 0, 44%) were treated at 11 Italian institutions from June 2016 and November 2018. 34% of the pts have been previously resected on their primary tumor, and 76% received gemcitabine-nabpaclitaxel as 1st - line treatment. 5FU/LV-nal-IRI has been administered as 2nd - line in 72% of the pts, while in 23% of the cases as 3rd - line or more. The median OS was 7.1 months [95% confidence interval (CI) 6.1 - 8.1] and the median PFS was 3.3 months (95% CI 2.9 - 3.6). At six months, OS and PFS rate were 53.4% and 31.4% respectively. ORR was 12% and DCR was 40%. 52% of pts received more than 4 cycle with dose reduction in 148 pts (50%). Most common grade 3 toxicities were neutropenia (14%), diarrhea (11%), anemia (3%), nausea (3%), fatigue (3%), mucositis (2%) and vomiting (1%). Baseline characteristics associated with better OS were ECOG PS 0, normal CEA, neutrophil-to-lymphocyte ratio ≤5 and haemoglobin ≥11 g/dL. Conclusions: These real-world data confirm the efficacy and safety of 5FU/LV-nal-IRI in patients with MPC progressed to a gemcitabine-based therapy, with outcome comparable to NAPOLI-1 even in a less selected population and with more active 1st - line combination therapy. In this cohort, well known prognostic markers has been confirmed, as expected.
Comparing survival outcomes for neoadjuvant therapy versus adjuvant therapy in the management of stage 1 pancreatic adenocarcinoma: A National Cancer Database study.
Authors: Datta Samit Kumar , Bellini Geoffrey , Singh Maharaj , Sich Nicholas , Weese James L. , Sanchez Federico Augusto , Guda Nalini , Papenfuss Wesley Allan , Chevinsky Aaron 
Published: February 2020

664 Background: We are in the midst of a paradigm shift in the treatment of stage 1 pancreatic ductal adenocarcinoma (PDAC) from surgery first followed by adjuvant therapy (AT) to Neoadjuvant therapy (NAT) first followed by surgery and this is reflected in the current NCCN guidelines as well. Data comparing these two modalities are limited. AIM: To compare long term survival between Surgery + AT and NAT + Surgery in a large National Cancer Database for stage 1 PDAC. Methods: We identified patients with the NCDB with surgically resected AJCC clinical stage 1, 1A, and 1B PDAC between 2004-2016. Patients were stratified into two groups to assess outcomes: AT and NAT. Patients with incomplete survival and sequence of therapy were excluded. Baseline demographic data, 90-Day Mortality, Median survival, and Hazard ratios (HR) for survival was evaluated. Results: 9017 pts with Clinical stage 1, 1A, 1B PDAC between 2004-2016 were identified. Of these 7453 pts had surgery followed by AT; and 1564 pts had NAT followed by surgery. There was a statistically significant difference in age (66.0±9.9 years for AT vs. 64.7±9.78 years for NAT, p &lt; 0.001) but no difference in Charlson Comorbidity Scoring (p = 0.618) or sex (p = 0.073). 90-Day Mortality was 0.35% in the AT group compared to 0.83% in the NAT group (p = &lt; 0.001). Median survival was 28.5 (95% CI 26.5-29.9) months in the NAT group compared to 25.4 (95% CI 24.7-26.1) months in the AT group. With AT as the reference group for survival, there was a HR of 0.904 (95% CI 0.845-0.968, p = 0.003) for NAT. Conclusions: In this retrospective cohort of patients, NAT was associated with increased overall survival. However, NAT was associated with an increased 90 day mortality. A randomized, controlled trial is necessary to further support the superiority of NAT in the management of stage 1 PDAC.
Changes in glucose tolerance after pancreatectomy in patients with pancreatic ductal adenocarcinoma.
Authors: Shirakawa Sachiyo , Toyama Hirochika , Komatsu Shohei , Ishida Jun , Kido Masahiro , Fukumoto Takumi 
Published: February 2020

668 Background: Diabetes mellitus (DM) is reported to be related to pancreatic ductal adenocarcinoma (PDAC). Long-standing DM is a risk factor for PDAC, meanwhile, quite a few patients with PDAC develop DM as a paraneoplastic disorder and some papers reported that DM affected prognosis for PDAC. In this study, we investigated pre- and post-operative glucose tolerance in patients with pancreatectomy for PDAC or other disease. Methods: This single-center prospective study included 69 patients with pancreatectomy (40 pancreaticoduodenectomy (PD) and 29 distal pancreatectomy (DP) ) who received 75-g oral glucose tolerance test (OGTT) and glucagon test pre- and one month postoperatively. Plasma glucose, insulin, and C-peptide (CPR) at 0-, 30-, 60-, and 120-min during OGTT; and 0- and 6-min during glucagon test were obtained. These data and survival outcomes were analyzed. Results: There were 20 (29%) PDAC patients: 12 (30%) in PD group and eight (28%) in DP group. Nine patients with PDAC (45%) and seven patients (18%) without PDAC demonstrated DM type in preoperative OGTT. After pancreatectomy, 11 patients (55%) with PDAC and seven patients (15%) without PDAC experienced improvement in OGTT (P=0.0005). Greater improvement in homeostasis model assessment insulin resistance that were obtained by OGTT and used to measure insulin resistance, was noted after surgery in PDAC patients compared with non-PDAC patients (-1.4 vs -0.5 in PD group, P=0.07; -0.8 vs +0.06 P=0.05 in DP group). Delta CPRs obtained by glucagon test were significantly decreased postoperatively (3.0 to 1.1 ng/mL, P<0.0001 in PD group; 3.3 to 1.8 ng/mL, P<0.0001 in DP group). In survival analysis, fasting plasma glucose >110 mg/dL (HR 3.9, 95%CI 1.5-10, P=0.005) and the average of plasma insulin > 25 µIU/mL during OGTT (HR 0.36, 95%CI 0.14-0.93, P=0.035) were significant prognostic factor for PDAC. Conclusions: Pancreatectomy impaired insulin secretion and improve insulin resistance especially in PDAC patients. About half of PDAC patients demonstrated the improvement of glucose tolerance after surgery. Of note, glucose tolerance differed between PDAC and other disease, and affect the survival outcome for PDAC patients.
A multicenter clinical randomized phase II study of investigating duration of adjuvant chemotherapy with S-1 (six versus 12 months) for patients with resected pancreatic cancer: PACS-1 study.
Authors: Yamashita Yo-ichi , Itoh Shinji , Shimokawa Mototsugu , Takamori Hiroshi , Fukuzawa Kengo , Ninomiya Mizuki , Araki Kenichiro , Kajiyama Kiyoshi , Sugimachi Keishi , Uchiyama Hideaki , Morine Yuji , Utsunomiya Tohru , Uwagawa Tadashi , Maeda Takashi , Adachi Eisuke , Ikeda Yasuharu , Yoshizumi Tomoharu , Baba Hideo , Mori Masaki 
Published: February 2020

669 Background: Although adjuvant chemotherapy with S-1 has improved overall survival and progression-free survival (PFS) in patients with resected pancreatic cancer, the duration evaluation of adjuvant chemotherapy with S-1 have not established yet. Methods: We did a randomized, multicenter, phase 2 trial undertaken at 15 hospitals in Japan. Patients who were Eastern Cooperative Oncology Group performance states of 0 or 1 and aged 20 years or older were eligible. Patients with resected pancreatic cancer were randomly assigned (in a 1:1 ratio) to receive S-1 [40 mg, 50 mg, or 60 mg according to body-surface area, orally administered twice a day for 28 days followed by a 14 day rest, every 6 weeks [one cycle], for up to four cycles (6 months)] or up to eight cycles (12 months). The primary end point was overall survival rate. Secondary endpoints included PFS and safety. Results: The population consisted of 82 patients in the S-1 for 6 months group and 82 patients in the S-1 for 12 months group. The 2-year overall survival rate was 71.4% in the S-1 for 6 months group and 65.4% in the S-1 for 12 months, and the median overall survival was 31.0 months in the S-1 for 6 months group and 26.3 months in the S-1 for 12 months group [hazard ratio (HR) 1.23, 95% confidence interval (CI) 0.76-1.99, p = 0.377]. The PFS at 2 years was 56.8% in the S-1 for 6 months group, and 51.2% in the S-1 for 12 months. The HR for recurrence of S-1 for 6 months, compared with S-1 for 12 months, was 1.23 (95%CI 0.76-1.99, p = 0.392). Twenty-nine (35.3%) patients in the S-1 for 6 months group and 46 (56.0%) in the S-1 for 12 months group discontinued treatment before completion. In regard to patients completed treatment, the S-1 for 12 months group showed tendency to favorable prognosis on PFS compared with the S-1 for 6 months group (log-rank test; p = 0.175). Conclusions: In patients with resected pancreatic cancer, adjuvant chemotherapy with S-1 for 12 months is not superior to that for 6 months in terms of median overall survival and PFS. For patients who can tolerate adjuvant chemotherapy with S-1 for 6 months well, continuing treatment for up to 12 months may improve the prognosis.
Real-world rates of hematology lab abnormalities and associated cost among metastatic pancreatic cancer (mPC) therapeutic regimens.
Authors: Dieguez Gabriela , Surinach Andy , Mercer Daniel , Cockrum Paul , Kim George P. , Pelizzari Pamela 
Published: February 2020

670 Background: Low hematologic counts are a common, costly side effect of chemotherapy. This observational study examines rates and associated cost to treat. Methods: Data on adverse events (AEs) were extracted from the clinical Flatiron Health database for mPC patients (pts) from 01/2014-01/2019. Anemia, neutropenia, and lymphopenia occurrence was assessed via diagnosis codes and structured lab data. Costs due to AEs were derived from a claims analysis of mPC pts from 2013-2017 in Medicare Limited Data Set claims. Mean adjusted incremental costs (ICs) were estimated by comparing 30-day costs of pts with and without AEs, with controls selected among pts without AEs with the same regimen and line of therapy, when at least 80 cases/controls were identified. Results: 4592 treated mPC pts were identified (median age at diagnosis: 68y, IQR: 61 – 75). 1138 pts were treated with FOLFIRINOX (FFX) in first-line (1L), 2295 pts with 1L gemcitabine plus nab-paclitaxel (gem-nab), 218 pts with second-line (2L) FOLFOX, 56 pts with 2L FOLFIRI, and 178 pts with 2L liposomal irinotecan (nal-IRI) based therapy. Observed rates of anemia and neutropenia are shown in the table below. Lymphopenia rates were similar across regimens and ICs were not statistically significant. ICs for patients with any grade anemia were $3864, $3818, $3536, $3978, and $2963 for FFX, gem-nab, FOLFOX, FOLFIRI, and nal-IRI treated pts, respectively. ICs for pts with any grade neutropenia were $2382 for FFX, $2440 for gem-nab, $2688 for FOLFOX, $3551 for FOLFIRI and $2307 for nal-IRI. Conclusions: Any grade anemia ICs ranged from $2963 [$1544, $4400] (nal-IRI) to $3978 [$2241, $5817] (FOLFIRI), and any grade neutropenia ICs ranged from $2307 [$703, $4313] (nal-IRI) to $3551 [$1227, $6039] (FOLFIRI). Pts treated with nal-IRI had similar any grade AE rates but lower ICs, which suggest lower severity of AEs. These results are consistent with Flatiron Health’s lower rates of grades 3+ neutropenia and anemia. [Table: see text]
Development and validation of a pancreatic cancer prediction model from electronic health records using machine learning.
Authors: Appelbaum Limor , Cambronero Jose Pablo , Pollick Karla , Silva George , Stevens Jennifer P. , Mamon Harvey J. , Kaplan Irving D. , Rinard Martin 
Published: February 2020

679 Background: Pancreatic Adenocarcinoma (PDAC) is often diagnosed at an advanced stage. We sought to develop a model for early PDAC prediction in the general population, using electronic health records (EHRs) and machine learning. Methods: We used three EHR datasets from Beth-Israel Deaconess Medical Center (BIDMC) and Partners Healthcare (PHC): 1. “BIDMC-Development-Data” (BIDMC-DD) for model development, using a feed-forward neural network (NN) and L2-regularized logistic regression,randomly split (80:20) into training and test groups. We tuned hyperparameters using cross-validation in training, and report performance on the test split. 2. “BIDMC-Large-Data” (BIDMC-LD) to re-fit and calibrate models. 3. “PHC-Data” for external validation. We evaluate using Area Under the Receiver Operating Characteristic Curve (AUC) and compute 95% CI using empirical bootstrap over test data. PDAC patients were selected using ICD9/-10 codes and validated with tumor registries. In contrast to prior work, we did not predefine feature sets based on known clinical correlates and instead employed data-driven feature selection, specifically importance-based feature pruning, regularization, and manual validation, to identify diagnostic-based features. Results: BIDMC-DD included demographics, diagnoses, labs and medications for 1018 patients (cases = 509; age-sex paired controls). BIDMC-LD included diagnoses for 547,917 patients (cases = 509), and PHC included diagnoses for 160,593 patients (cases = 408). We compared our approach to adapted and re-fitted published baselines. With a 365-day lead-time, NN obtained a BIDMC-DD test AUC of 0.84 (CI 0.79 - 0.90) versus the previous best baseline AUC of 0.70 (CI 0.62 - 0.78). We also validated using BIDMC-DD’s test cancer patients and BIDMC LD controls. The AUC was 0.71 (CI 0.67 - 0.76) at the 365-day cutoff. NN’s external validation AUC on PHC-Data was 0.71 (CI 0.63 - 0.79), outperforming an existing model’s AUC of 0.61 (CI 0.52 - 0.70) (Baecker et al, 2019). Conclusions: Models based on data-driven feature selection outperform models that use predefined sets of known clinical correlates and can help in early prediction of PDAC development.