bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nab-paclitaxel plus gemcitabine versus FOLFIRINOX in the first-line chemotherapy for patients with advanced pancreatic ductal adenocarcinoma: A national cohort (Comunica-TTD working group).
Authors: Longo Federico , Castillo Trujillo Oscar Alfredo , Serrano Domingo Juan José , Huertas Roberto Martin , Corral de la Fuente Elena , San Juan del Moral Alberto , Portela Jaime , Cano Juana Maria , Reguera Puertas Pablo , Rodríguez Garrote Mercedes , Izquierdo Manuel Marta , Jiménez-Fonseca Paula , Carrato Alfredo , Aranda Enrique 
Published: May 2019

e15707 Background: Advanced pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a five-year overall survival (OS) of less than 5%. Folfirinox and Nab-Paclitaxel plus Gemcitabine (NabPacGem) are the most active treatments in the first-line (1L). The decision to use Folfirinox or NabPacGem is a matter of debate. Methods: A retrospective cohort of advanced PDAC patients treated from January 2011 to May 2018 in four Spanish institutions was analyzed. The principal objective was to compare OS among patients receiving Folfirinox versus NabPacGem in 1L. Progression-free survival (PFS) was a secondary objective. Results: Characteristics of 251 patients included: median age 66.6 years; male 54.4%; stage IV at diagnosis 66.7%; ECOG 0/1/2 18/70/12%; treated with Folfirinox 18.3% and NabPacGem 81.7%. Patients treated with Folfirinox versus NabPacGem were younger (median age 58.3 vs. 67.9; p<0.001) and had lower ECOG (0/1/2 of 46/54/0% vs. 13/71/16%; p<0.001). Univariate analysis: median PFS 5.8 months (95%CI, 4.3 – 7.3) for Folfirinox and 4.2 months (95%CI, 3.7 – 5.2) for NabPacGem, HR=1.53 (95%CI, 1.1 – 2.1; p=0.012); median OS 12.7 months (95%CI, 8.4 – 14.3) for Folfirinox and 7.6 months (95%CI, 5.8 – 8.8) for NabPacGem, HR=1.38 (95%CI, 0.96 – 1.98; p=0.081). Multivariate Cox analysis (including type of treatment, ECOG and age) showed that ECOG was the only variable associated with PFS and OS (Table). Conclusions: In our study, advanced PDAC patients treated with Folfirinox were younger and had a better performance status than those treated with NabPacGem. We found no differences in survival between both treatments when adjusting by ECOG and age.[Table: see text]
Immune landscape of neoadjuvant/preoperative chemoradiotherapy in pancreatic cancer.
Authors: Nakajima Kosei , Ino Yoshinori , Hiraoka Nobuyosh 
Published: May 2019

e15709 Background: Neoadjuvant/preoperative chemoradiotherapy in pancreatic cancer has been implicated to induce a local anti-tumor immunity, however the molecular mechanism remains a conundrum. Methods: Two patients’ cohort samples with/without preoperative chemoradiotherapy were used (n = 26 and n = 20, respectively). The treatment-driven immune microenvironment changes were analyzed by stratified bioinformatic approaches i.e. heat map analysis of immune-related genes selected by Gene Ontology, GSEA with Immunologic Signature data base, and Ingenuity Pathway Analysis (IPA). The results were further validated by immunohistochemical approaches. Results: Preoperative treatment induced 212 genes including DC-SIGN (CD209) and 13 immune-associated pathways such as TCR signaling, with an increasing shift of CD8 T-cell population by upregulation of MAL (T-cell differentiation protein). Consistently, immunohistochemical findings showed that the accumulation of DC-SIGN (+) dendritic cells and MAL (+) lymphocytes were significantly increased in patients with preoperative therapy. Conclusions: Preoperative chemoradiotherapy induces a shift toward CD8 T-cell generation mediated by DC-SIGN (+) dendritic cells and MAL (+) lymphocytes, leading to enhance anti-tumor immunity.
Remnant pancreatic volume to predict short-term and long-term outcomes in patients with resected pancreatic cancer.
Authors: Miyamoto Ryoichi , Oshiro Yukio , Ohkohchi Nobuhiro 
Published: May 2019

e15713 Background: Remnant pancreatic volume (RPV) is a well-known marker for short-term outcomes in patients with resectable pancreatic cancer. However, in terms of the long-term outcomes, the significance of the RPV remains unclear. Here, we addressed whether the RPV is a predictor of long-term outcomes in pancreatic cancer patients by comparing various cancer-, patient-, and surgery-related prognostic factors and systemic inflammatory response markers in a retrospective cohort. Methods: The RPV was measured on the 3D image, revealing the actual pancreatic parenchymal remnant volume. Ninety-one patients who underwent pancreaticoduodenectomy (PD) were retrospectively enrolled. We divided the cohort into high- and low-RPV groups based on a cut-off value ( > 35.5 cm3, n = 66 and ≤ 35.5 cm3, n = 25, respectively). The patient characteristics, perioperative outcomes and median survival times (MSTs) were respectively compared between the two groups. Using multivariate analysis, the RPV and other well-known prognostic factors were independently assessed. Results: A significant difference in the RPV value was observed with respect to the incidence of postoperative pancreatic fistula (high, 18 [55%] vs. low, 9 [16%], p < 0.001). The MSTs (days) were significantly different between the two groups (high, 823 vs. low, 482, p = 0.001). Multivariate analysis identified the RPV (≤ 31.5 cm3) (hazard ratio [HR], 2.015; p = 0.011), lymph node metastasis (HR, 8.415; p = 0.002), adjuvant chemotherapy (HR, 5.352; p < 0.001), presence of stage III/IV disease (HR, 2.352; p = 0.029), and pathological fibrosis (HR, 1.771; p = 0.031) as independent prognostic factors. Conclusions: The present study suggests that the RPV is an additional useful predictor of both long-term and short-term outcomes in pancreatic cancer patients after PD.
Treatment response and survival in patients with pancreatic adenocarcinoma receiving neoadjuvant chemotherapy or chemoradiation.
Authors: Khattab Ahmed , Patruni Sunita , Abel Stephen , Hasan Shaakir , Finley Gene Grant , Monga Dulabh K. , Wegner Rodney E , Verma Vivek 
Published: May 2019

e15715 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Neoadjuvant chemotherapy (NeoChT) and chemoradiation (NeoCRT) have emerged as strategies to optimize resection, but data investigating predictors of treatment response and the overall survival (OS) impact are not well characterized. To investigate the effects of NeoChT/NeoCRT on primary tumor/nodal downstaging and OS, we analyzed the national cancer database (NCDB). Methods: We queried the NCDB for patients with PDAC receiving NeoChT/NeoCRT. Patients were classified as responders (T and/or N downstage), nonresponders (mixed/no response) and progressors (T and/or N upstage). Multivariable logistic regression identified predictors of response. Univariable and multivariable analyses identified characteristics predictive of OS. Results: 2,028 patients with PDAC receiving NeoChT/NeoCRT were analyzed. Univariable analysis of responders (n = 790) vs. nonresponders/progressors (n = 1,238) demonstrated a significant difference in median OS at 29.1 months vs. 25.3 months and 3-year overall survival of 40% vs. 34% [p = 0.006; HR: 0.95 (95% CI: 0.84-1.08)] respectively. When compared independently to both responders and nonresponders, progressors had a significantly decreased 3-year OS at 31% vs 40% and 37% respectively [p = 0.003; HR: 0.82 (95% CI: 0.70-0.96)]. Predictors of response on multivariable logistic regression included receipt of multiagent chemotherapy and receipt of NeoCRT. Only NeoCRT predicted for pathologic complete response (pCR). Multivariable analysis of patients with pCR demonstrated a trend towards increased OS (p = .08). Conclusions: Our results suggest that both response and progression following neoadjuvant therapy may predict for longer and shorter OS respectively. Randomized, prospective studies are needed to further validate these findings. [Table: see text]
Change in body composition and survival in patients with pancreatic cancer.
Authors: Krishnan Mridula , Yu Lei , Dasgupta Aneesha , Mullen Nicholas J , Osayande Ferdinand , Berim Lyudmyla Derby , Alam Morshed , Yu Fang , Oliveto Jennifer , Klute Kelsey , Singh Pankaj K. 
Published: May 2019

e15716 Background: The incidence of pancreatic ductal adenocarcinoma (PDAC) is on the rise and continues to have a poor overall survival despite aggressive available treatment strategies. Sarcopenia is prevalent in PDAC patients and is likely caused by both disease and treatment. We hypothesized that ongoing muscle loss during treatment with chemotherapy would be associated with shorter progression-free survival (PFS) and overall survival (OS). Methods: We measured skeletal muscle index at L3 vertebra on baseline follow-up scans in patients with PDAC treated with chemotherapy at our institution. Patients were categorized by percent SMI lost over an 8-week period (<10%, 10-20%, ≥20% loss). We compared PFS and OS between the groups. Results: We included 162 patients with stage I-IV pancreatic cancer. Baseline characteristics are listed in the Table. SMI loss was associated with shortened PFS and OS (p=0.009, p=0.032 respectively) via log-rank test for trend. Even after adjusting for confounders (age, gender, resection status, stage, baseline sarcopenia, treatment and therapy), the relative risk of death (2.0; 95% CI=1.10-3.64, p=0.023), and progression (1.83; 95% CI =1.08-3.10, p =0.024) were higher in those who lost ≥20% SMI. There was no significant association between BMI change or fat change with the survival outcomes. Conclusions: The loss of skeletal muscle during the first 8 weeks of chemotherapy is associated with shortened survival outcomes and is independent of stage and resection status in patients receiving chemotherapy for PDAC. Future studies should seek to understand mechanisms of muscle loss by both tumor and chemotherapy to improve survival in patients with PDAC. Baseline characteristics. [Table: see text]
Effect of neoadjuvant chemotherapy using gemcitabine and S1 before surgery for pancreatic cancer on quality of life.
Authors: Sato Naoko , Motoi Fuyuhiko , Iseki Masahiro , Kawaguchi Kei , Sato Fumiko , Katayose Yu , Unno Michiaki 
Published: May 2019

e15719 Background: To improve the poor prognosis of patients with pancreatic cancer, we examined the effect of 6 months of neoadjuvant chemotherapy (NAC) using gemcitabine and S1 before surgery and found significantly prolonged survival. Clinical use of this treatment is expected in the future. However, preoperative NAC may increase the physical burden on patients as well as their psychological burden due to the longer waiting time. Thus, it is necessary to confirm that the treatment does not reduce quality of life (QOL). Methods: In this observational study of patients who underwent resection after this NAC, a QOL questionnaire survey was administered preoperatively and at postoperative months 3, 6, and 12, to consenting patients from those enrolled in randomized controlled trials (RCTs). The intervention group (planned surgery and NAC) had added pre- and post-treatment QOL surveys. We used the Short Form 36 Health Survey version 2 (SF-36v2 Standard, Japanese) to measure health-related QOL. Overall differences among the groups were evaluated by paired t test and two- and three-way ANOVA. All statistical analyses were performed using SPSS (ver. 21) software. Results: In total, 55 patients (mean age 66.0 years), about 15% of those enrolled in the RCTs, responded to the questionnaire (NAC group, n = 22; control group, n = 33). QOL was not significantly reduced in the NAC group pre- and post-treatment ( p= 0.19-0.96). Notably, there were no significant differences in post-treatment QOL, with improvement in the Physical Functioning (75.9→79.4), Bodily Pain (70.5→72.5), Vitality (59.6→59.9), and Mental Health (66.5→69.7) SF-36 domains compared with before preoperative treatment. This suggests that patients had good preoperative physical and mental QOL. QOL at each time point did not differ significantly in the 8 domains with or without NAC; the Mental component summary score was significantly higher in the NAC group compared with the control group at 3 months (54.9 vs 49.3, p= 0.04). NAC and QOL did not differ significantly by time, sex, and operation type. Conclusions: NAC using gemcitabine and S1 before surgery for pancreatic cancer does not reduce QOL. Improved prognosis can be expected with no adverse effect on QOL.
Effect of irreversible electroporation (IRE) combined with chemotherapy (C) on survival in locally advanced pancreatic cancer (LAPC) patients (pts).
Authors: Karamouzis Michalis , Oikonomou Dimitrios , Dimitrokallis Nikolaos , Papamichael Demetris , Kountourakis Pantelis , Astras George , Moris Demetrios , Davakis Spyridon , Papalampros Alexandros , Petrou Athanasios S , Felekouras Evangelos 
Published: May 2019

e15723 Background: LAPC represents 40% of PC pts. IRE is a non-thermal ablative technique that can be used in inoperable pts and safely combined with C. Methods: From 2015 to 2018 laparotomic IRE was performed in a total of 34 LAPC pts. The median age was 64.7yrs (range, 46-81yrs) and 15 (44%) were males. The median tumor size was 3.9cm (range, 2-5.2cm) with the majority of tumors located at pancreatic head (26 pts, 76%), followed by body (6 pts, 18%) and tail of pancreas (2 pts, 6%). Induction C was applied in 27 out of 34 pts and in case of disease control IRE was done, while in 7 pts IRE was done without prior C. In the majority of pts C after IRE was also given. Results: Induction C was applied in 27 out to 34 pts (80%) [FOLFIRINOX in 16 pts, nab-paclitaxel-gemcitabine (AG) in 11 pts]. After the completion of 3 cycles of C tumor evaluation showed partial response (PR) in 20 pts and stable disease (SD) in 7 pts. All pts were treated with IRE and 50% of them had a preoperative biliary stent, while 3 pts had metallic stent that was removed before IRE. No IRE-related deaths occurred. Two major complications grade III were reported: pancreatic fistula grade A in 7 pts and 2 pts diagnosed with delayed gastric emptying. There was also one minor complication (wound infection) in 3 pts (9%). Up to 31/12/2018, the median overall survival (OS) of all pts was 24.2 months (mos) (range, 6-36 mos) and median progression free survival (PFS) was 14.6 mos (range, 3-24 mos). The median OS of the pts treated with C-IRE-C was 22.5 mos (range, 13-36 mos) and median PFS 16.9 mos (range, 3-24 mos), while in pts treated with IRE-C only was 15 mos (6-22 mos) and 10.9 mos (range, 5-16 mos), respectively. The group treated with FOLFIRINOX-IRE-C showed median OS 22.5 mos (range, 15-36 mos) and median PFS 17.1 mos (range, 3-24 mos), while the group treated with AG-IRE-C had median OS 19 mos (range, 13-36 mos) and median PFS 15.8 mos (range, 7-24 mos). After IRE, 24 pts (71%) continued with adjuvant C, either FOLFIRINOX 5 pts (15%) or G-based regimen 18 pts (46%) until disease progression or unacceptable toxicity, while 12 pts (35%) have more than 24 mos OS and 3 pts (9%) have reached 36 mos OS and are still alive. Conclusions: The combination of C with IRE is safe and results in survival increase of LAPC pts. Pts treated with the sequence FOLFIRINOX-IRE-C seems to benefit the most.
Main driver genes and BRCA mutation in Chinese patients with pancreatic adenocarcinoma.
Authors: Tian Jiangfang , He Du , Huang Zhixi , Tian Bole , Cao Dan 
Published: May 2019

e15741 Background: Data on pathogenic genetic alterations in Chinese patients with pancreatic adenocarcinoma (PAC) are limited. Especially, as BRCA mutations may become potential biomarkers guiding therapy for PAC patients, the prevalence of BRCA mutations in Chinese patients remains largely unknown.We performed the study to analyze genes mutational landscape and determine the prevalence of BRCA mutations in Chinese PAC patients. Methods: We reviewed clinical characteristics and genes mutations of 134 patients with a pathologically confirmed PAC from West China Hospital of Sichuan University between May 2016 and November 2018. All of them underwent gene-testing and genes variant evaluation with a panel of 381 genes by next-generation sequencing (NGS). The test samples were mainly from primary pancreatic lesions, other were from peripheral blood and metastatic sites. All main driver gene mutations and clinical stages were measured to determine associations of driver gene mutations, the number of altered genes, the level of CA199 with clinical stage. Results: Of the 134 patients, 73 (54.5%) were men with a median age of 58 (range from 34 to 82) years. The major driver mutations were KRAS (89.6%), TP53 (71.6%), CDKN2A (26.9%), SMAD4 (18.7%) and ARID1A (10.4%). The majority of patients (76.9%) had 2 genes or more genes mutations, KRAS/TP53 and KRAS/TP53/CDKN2A were the most frequently combinate types. Stages of PAC was relevant to numbers of altered genes (p = 0.040) and the level of CA199 (p = 0.002). Five (3.7%) patients with BRCA mutations were identified, two patients had somatic BRCA2 variants, one patient had somatic BRCA1 mutation and the other two patients had germline BRCA2 mutation. Two patients with germline BRCA2 mutations received olaparib and keep stable disease for 4 months and more than 8 months. Our finding revealed patients with PAC had a low TMB (median 3.81 per Mb (range 0.81-9 per Mb)) and PD-L1 expression (16/36, 44.4%), nearly all of them were MSS (50/51,98.0%), just three patients with dMMR (3/134,2.2%). Conclusions: The PAC patient commonly harbored two or more number of five major driver mutations including KRAS, TP53, CDKN2A, SMAD4 and ARID1A. The frequency of BRCA1/2 mutations in Chinese patients with PAC was 3.7%. Olaparib may be effective for PAC patients with BRCA mutations. The PAC may be poor response to immunotherapy.
Role of neoadjuvant therapy (NAT) in pancreatic adenocarcinoma (PAC): A single center experience.
Authors: Nassabein Rami Mohamad , Richard Corentin , Ayoub Jean-Pierre M. , Aubin Francine , Campeau Marie-Pierre , Delouya Guila , Donath David , Dagenais Michel , Lapointe Real W. , Letourneau Richard , Plasse Marylene , Turcotte Simon , Roy Andre , Vandenbroucke-Menu Franck , Olivié Damien , Routy Bertrand , Tehfe Mustapha 
Published: May 2019

e15747 Background: Surgical resection of PAC followed by adjuvant therapy is the standard of care for non-metastatic resectable tumors. Surgical resection with clear margins of borderline (BR) or locally advanced (LA) tumors is either challenging or impossible. Furthermore, there are no clear recommendations concerning NAT for non-upfront resectable PAC. Thus we reviewed our own experience with different NAT modalities for BR and LA PAC. Methods: Medical records of patients identified by Tumor Board as BR or LA PAC and treated with NAT at Centre Hospitalier de l’Université de Montréal (CHUM) were retrospectively reviewed. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test. For both univariate and subgroup analyses, hazard ratio and 95% confidence interval were estimated by Cox proportional hazard regression. Results: Between 2009 and 2017, 90 patients (50 BR, 40 LA) were identified. Chemotherapy, mostly FOLFIRINOX, was the only NAT in 51 patients (56.6%), 23 patients (25.3%) received chemoradiotherapy alone and 16 patients (17.7%) received sequential treatment of both modalities. Tumor resection was achieved in 44 patients, with 32 BR patients (R0: 68.7%) and 12 LA patients (R0: 75%). Median Disease free survival (DFS) of patients that underwent resection was 12.3 months. mPFS was 29 vs 10 months (HR:0.2; p < 0.001) and mOS was 41.7 vs 15.7 months (HR:0.3; p < 0.001) in resected and non-resected patients, respectively. In subgroup analysis, resection statistically improved PFS and OS regardless of age, sex, T stage and type of vessel involvement. Treatment with more than one modality showed better clinical outcomes (PFS and OS) and a non-statistically higher R0 resection rate that was 100% in BR tumors. OS in patients with resected cancers was not reached for the multimodality group, 41.7 months for chemotherapy alone group and 22.4 months in patients treated with chemoradiotherapy group (p = 0.017). Conclusions: In this retrospective single center analysis, NAT with chemotherapy and/or chemoradiotherapy appears to improve patients’ clinical resection results and outcomes. These results validate previous retrospective studies but warrant large prospective trials to define the best NAT.
Comprehensive genomic analysis of metastatic pancreatic ductal adenocarcinoma (mPDAC) reveals a significant proportion of clinical actionable aberrations.
Authors: Lee Michael , Jones Martin R , Williamson Laura , Topham James Thomas , Wong Hui-Li , Addison Sean , Denroche Rob , Jang Gun Ho , Karasinska Joanna , McGhie John Paul , Gill Sharlene , Lim Howard John , Yip Stephen , Knox Jennifer J. , Gallinger Steven , Laskin Janessa J. , Marra Marco A. , Jones Steven J. M. , Schaeffer David F. , Renouf Daniel John 
Published: May 2019

e15753 Background: Significant progress has been made in the understanding of the genomic landscape of PDAC, but the clinical utility of these data remains uncertain. Methods: As part of the BC Cancer Personalized Oncogenomics (POG) and PanGen studies (NCT02155621, NCT02869802), whole genome analysis and transcriptome sequencing were performed on fresh biopsy and blood sample from 48 mPDAC patients. Genomic findings informed therapy choices including potential eligibility for the CCTG PM.1 molecular basket trial (NCT03297606). Results: Cohort consists of 54.1% male, average age 57.6, 34/48 had ≥2 lines of treatment. 37/48 biopsies were from liver and 27/48 were collected pre-treatment. 8/48 (16.6%) patients had aberrations with strong evidence of clinical actionability. These include 2 germline BRCA2, 1 germline BRCA1, 1 somatic XRCC2 homozygous deletion with strong COSMIC signature 3, all predictive of platinum sensitivity. Patients with XRCC2 deletion and BRCA1 had over 2 years on FOLFIRINOX. Fusions affecting the NRG1 gene were identified in 3/4 patients with KRAS wildtype tumours, which may confer ERRB inhibitor sensitivity. 2/3 NRG1 fusion patients have thus far been treated with the ERBB inhibitor afatinib with radiographic responses noted in both patients. One patient had mismatch repair deficiency, and a high mutational burden, suggestive of immune checkpoint inhibitor sensitivity. Other possible actionable mutations include CCTG PM.1 trial potential eligibility: 4/48 with high homologous recombination defects and 1 germline ATM mutation loss (PARP inhibitor arm), 1/47 ERBB2 amplification (anti-HER2 arm), 2/47 high expression of FGFR1 (Sunitinib arm) and 1/47 with high FLT4 and IGF1R expression (Axitinib arm). Conclusions: More routine use of comprehensive genomic analysis should be considered in mPDAC given finding of high degree of actionability. Importantly, a significant proportion (16.6%) had findings with strong evidence of clinical impact.