bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase Ib study of gemcitabine, nab-paclitaxel, and ficlatuzumab in patients with advanced pancreatic cancer.
Authors: Perez Kimberly , Weekes Colin D. , Cleary James M. , Abrams Thomas Adam , Blaszkowsky Lawrence Scott , Enzinger Peter C. , Giannakis Marios , Goyal Lipika , Meyerhardt Jeffrey A. , Rubinson Douglas Adam , Yurgelun Matthew B. , Stonely Danielle , Raghavan Srivatsan , Bakir Basil , Das Koushik , Pitarresi Jason , Aguirre Andrew , Needle Michael N. , Rustgi Anil , Wolpin Brian M. 
Published: February 2020

693 Background: Paired-related homeodomain transcription factor 1 (Prrx1) isoforms are involved in pancreatic development, pancreatitis, and carcinogenesis. Hepatocyte growth factor (HGF) is a transcriptional target of Prrx1b. Ficlatuzumab is a recombinant humanized HGF antibody, that neutralizes HGF/c-Met binding and HGF-induced c-Met phosphorylation. In preclinical pancreatic ductal adenocarcinoma (PDAC) models, inhibition of Prrx1b-HGF signaling using ficlatuzumab and gemcitabine reduced primary tumor volume and eliminated metastatic disease. Methods: Patients (pts) with previously-untreated metastatic PDAC enrolled in a phase Ib dose escalation study with 3+3 design and two dose cohorts of ficlatuzumab (10mg/kg and 20mg/kg) administered intravenously every other week with gemcitabine (G; 1000mg/m2) and nab-paclitaxel (A; 125mg/m2) given 3 weeks on and 1 week off. This was followed by an expansion phase at the maximally tolerated dose (MTD) of the combination. Results: 24 pts (sex, 12M:12F; median age, 69 years [range, 51-82 years]) were enrolled. No dose-limiting toxicities were identified in the phase 1b (N = 6 pts) and ficlatuzumab at 20mg/kg with GA was advanced to the expansion phase (N = 18 pts). By RECISTv1.1 in the full study population, 7 (29%) pts had partial response, 15 (63%) had stable disease, and 2 (8%) could not be evaluated. Median progression-free survival was 8 months (range, 3-16 months), 4 pts are still on study treatment. The primary toxicities attributed to ficlatuzumab included hypoalbuminemia (grade 3, 21%; any grade, 91%) and edema (grade 3, 8%; any grade, 91%). Nine (38%) of the 24 pts discontinued study treatment due to these toxicities prior to disease progression. Conclusions: The combination of ficlatuzumab with gemcitabine and nab-paclitaxel is associated with durable treatment responses but also significant hypoalbuminemia and edema that may impair treatment tolerability. Serial blood samples were collected for circulating HGF measurements, and mandatory pretreatment biopsies were collected for tumor c-MET pathway activation and 3D organoid culture drug sensitivity testing. Clinical trial information: NCT03316599.
The development of therapeutic cancer vaccine for pancreatic cancer.
Authors: Yamaue Hiroki , Miyazawa Motoki , Katsuda Masahiro , Kawai Manabu , Hirono Seiko , Okada Ken-Ichi , Kitahata Yuji , Ueno Masaki , Hayami Shinya 
Published: February 2020

707 Background: A previous phase II/III trial using a single cancer peptide vaccine derived from vascular endothelial growth factor receptor (VEGFR)2 for patients with advanced pancreatic cancer did not demonstrate the overall survival (OS) benefit (Yamaue et al. Cancer Sci 2015). However, for the next trial, we conducted a multicenter phase II study using multipeptide cocktail vaccine named OCV-C01 derived from a novel higher immunogenic antigen KIF20A, VEGFR1 and VEGFR2 combined with gemcitabine in postoperative adjuvant setting. Methods: A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks, and gemcitabine was administered intravenously at 1,000 mg/m2 on days 1, 8, and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease-free survival (DFS) and secondary endpoints included safety, OS and immunological assays on peptide-specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. Results: The median DFS was 15.8 months (95% confidence interval (CI), 11.1-20.6), and the DFS rate at 18 months was 34.6% (95% CI, 18.3-51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8-82.5). The administration of OCV-C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with and without KIF20A-specific CTL responses (p = 0.027), and between patients with and without KIF20A expression in resected pancreatic cancer tissues (p = 0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A-specific CTL responses. Conclusions: OCV-C01 combined with gemcitabine was tolerable with a favorable median DFS of 15.8 months. In cancer vaccine treatment, positive expression of targeted antigen was essential, and postoperative adjuvant setting was more suitable than advanced state of cancer. Clinical trial information: UMIN000007991.
The role of immunotherapy on the survival of pancreatic cancer patients.
Authors: Amin Saber Ali , Baine Michael , Meza Jane L. , Lin Chi 
Published: February 2020

714 Background: Immunotherapy has revolutionized the treatment landscape of many malignancies, but its therapeutic role in pancreatic cancer (PC) remains unclear. The objective of this study is to investigate the impact of immunotherapy on the overall survival of PC patients stratified by definitive surgery of the pancreas using the National Cancer Database (NCDB). Methods: Patients with pancreatic adenocarcinoma were identified from NCDB. Cox proportional hazard models were employed to assess the impact of immunotherapy on survival after being stratified by surgery and adjusted for age of diagnosis, race, sex, place of living, income, education, treatment facility type, insurance status, year of diagnosis, and treatment types such as chemotherapy and radiation therapy. Results: Of 252,280 patients who were analyzed, 214,632 (85.08%) had definitive surgery, and 37,638 (14.92%) did not get definitive surgery of the pancreas. In the surgery group, 351 (0.93%) received immunotherapy and 37,287 (99.07%) did not while in the no surgery group, 838 (0.39%) received immunotherapy and 213,804 (99.61%) did not. In the multivariable analysis, patients who received immunotherapy had significantly improved OS both in the no surgery group (HR: 0.886, CI: 0.655-0.714; P < 0.0001) and in the surgery group (HR: 0.846, CI: 0.738-0.971; P < 0.0001) compared to patients who did not receive immunotherapy. Treatment with chemotherapy plus immunotherapy was associated with significantly improved OS (HR: 0.871, CI: 0.784-0.967; P < 0.009) compared to chemotherapy without immunotherapy in the no surgery group, while it was not significant in the surgery group. Chemoradiation plus immunotherapy was associated with significantly improved OS (HR: 0.787, CI: 0.684-0.906; P < 0.0009) in the no surgery group and (HR: 0.799, CI: 0.681-0.938) in the surgery group compared to chemoradiation alone. Conclusions: In this study, the addition of immunotherapy to chemoradiation therapy was associated with significantly improved OS in PC patients with or without definitive surgery. The study warrants further future clinical trials of immunotherapy in PC.
Role of para-aortic lymph node sampling in pancreatic cancer surgery.
Authors: Kazami Yusuke , Ito Hiromichi , Ono Yoshihiro , Sato Takafumi , Inoue Yosuke , Takahashi Yu 
Published: February 2020

715 Background: In the management of pancreatic cancer, para-aortic lymph node (PALN) metastasis is regarded as distant metastasis, and systemic treatment is recommended. However, imaging study is not perfect to detect all PALN metastasis and the management of intraoperatively discovered PALN has been controversial. We hypothesized that sampling of PALNs on exploration could allow us to avoid pancreatic resection for patients who would not benefit. In this study, we evaluated the incidence and the effect on the long-term outcomes for patients with potentially resectable pancreatic cancer. Methods: Three hundred and ninety-two patients who had PALNs sampled upon potentially resectable pancreatic cancer from 2005 through 2014 were included in the study. All patients were appropriately staged preoperatively with CT/MRI and those with suspected PALN metastasis were not considered as candidates for resection. The patients whose resections were aborted because of liver metastasis or peritoneal dissemination discovered on exploration, or those who died within 30-days after the operation were not included. Evaluated outcomes were incidence of PALN metastasis and their recurrence-free and overall survivals (RFS, OS). Results: The patients’ median age was 74 years, and 58.6% was man. 67.8% had tumors at pancreatic head. Preoperative chemotherapy was given only on 16 patients (3.2%). Among 392 patients with PALNs sampled, 53 (13.5%) patients had metastasis; Resection was completed on 40 patients and resection was aborted on the rest. Among patients who underwent pancreatic resection, median RFS and OS were 10 and 12 months for patients with PALN metastasis, compared to 17 and 26 months for those without PALN metastasis (p < 0.001 for RFS and p < 0.001 for OS). The 5-year-OS rates for patients with/without PALN metastasis were 5.9% and 25% (p < 0.001). Among 53 patients with PALN metastasis, OS were not different between the patients who underwent resection and those who did not (median 13 months vs 17 months, p = 0.06), and there were no recurrence-free survivors. Conclusions: PALN sampling and evaluation before committing to resection is useful to identify the patients who can unlikely benefit and to avoid unnecessary morbid operation.
Efficacy and safety of nab-paclitaxel plus S-1(nab-P/S-1) versus nab-paclitaxel plus gemcitabine (nab-P/Gem) for first-line chemotherapy in advanced pancreatic ductal adenocarcinoma (aPDAC): A randomized study.
Authors: Zong Yuan , Peng Zhi , Wang Xicheng , Shen Lin , Zhou Jun 
Published: February 2020

717 Background: Nab-P/Gem significantly improved survival compared with gem in patients (pts) with metastatic PDAC, but the ORR was limited to 23% with increased myelosuppression. Two phase II trials demonstrated high ORR of 50.0-53.1% with nab-P/S-1 and showed less hematologic toxicity. Methods: A randomized (1:1) phase II trial was conducted. Eligibility required treatment-naïve pts with unresectable PDAC. Pts received nab-P 125mg/m2on day 1 + S-1 80-120mg orally per day on day 1-7 every 2 weeks or nab-P 125mg/m2+ Gem 1000mg/m2 on days 1,8 every 3 weeks. With an increase of ORR from 25% to 50%, 100 pts were required for 90% power at a two-sided significance level of 0.05. We enrolled 40 pts for a pilot study. Primary endpoints were ORR and 6-month PFS rate. Secondary endpoints were ORR of primary lesion, DCR, PFS, OS and safety. Results: 40 pts were enrolled between 06/2018 and 06/2019, including locally advanced (27.5%) and metastatic (72.5%) PDACs. 42.5% were male and the median age was 61 (range, 36-75) years old. The median duration of treatment was 2.3 months in nab-P/S-1 (n = 20) and 2.7 months in nab-P/Gem (n = 20). In the intention-to-treat (ITT) population, the ORR and DCR were 35.0% vs 25.0% ( P= 0.49) and 70.0% vs 70.0%, respectively.The ORR of primary lesion was 30.0% vs 25.0% ( P= 0.72). In the evaluable pts (nab-P/S-1 n = 18, nab-P/Gem n = 18), the ORR, DCR and the ORR of primary lesion were 38.9% vs 27.8%, 77.8% vs 77.8% and 35.3% vs 29.4%, respectively.With the median follow-up of 5.0 (range 0.3-11.4) months, the median PFS and 6-month PFS rate was 6.3 vs 5.7 months and 56.1% vs 36.2%( P= 0.61) for nab-P/S-1 and nab-P/Gem, respectively. The median OS have not reached. Grade 3/4 toxicities occurred in 30.0% nab-P/S-1 and 30.0% nab-P/Gem: leukopenia/neutropenia(15.0% vs 25.0%), febrile neutropenia (0 vs 5.0%), rash (0 vs 5.0%) and diarrhea (10.0% vs 0). Conclusions: Compared with nab-P/Gem, nab-P/S-1 had higher ORR, ORR of primary lesion and longer PFS without significant difference. Nab-P/S-1 developed a trend towards less hematologic toxicity. Follow up for survival is ongoing. Clinical trial information: 03636308.
Neoadjuvant gemcitabine and nab-paclitaxel followed by concurrent capecitabine/radiation in borderline resectable (BR) pancreatic cancer: A single-institution experience.
Authors: Gupta Niraj K. , Singh Kirpal , Aburajab Murad , Mathavan Vinay , Al-Satie Mazen , Glass Timothy , Leagre Christopher A. , Rowe Michael , Tigges Thomas , Liebross Robert H. , Davis Chad , Tandra Sweta , Tumati Vas , Tian Jianmin , Martinez Brandon , Dowell Joshua , Schmidt Kristen Kay , Flanders Vincent ,   St Vincent Cancer Care
Published: February 2020

718 Background: Neo-adjuvant therapy is becoming a preferred approach in the management of BR pancreatic cancer patients. There is no consensus on an ideal treatment regimen. We report our experience with a combination of nab-Paclitaxel/Gemcitabine followed by concurrent Capecitabine and radiation treatments in BR pancreatic cancer patients. Methods: A prospectively maintained database of patients with BR pancreatic cancer undergoing neo-adjuvant treatments at our cancer center between 01/2013- 11/2017 was reviewed. Patients were treated with Gemcitabine(1gm/m2) and nab-paclitaxel (125mg/m2) given on D1-8-15 every 28 days. Pts. were re-assessed after two cycles and the responding pts received two additional cycles. Pts. who continued to respond after four cycles were treated with capecitabine (825mg/m2) and radiation treatments(50.4Gy). Results: A total of 32 patients with PS 0/1 were treated. Median age was 59 yrs (42-76), 19 Males and 13 females. After 2 cycles of Gem/nab-paclitaxel, none of the pts. had progressive disease. Thirty patients (93%) were able to complete all four cycles of Gem/nab-paclitaxel. Twenty nine (90%) received capecitabine and radiation treatments. Imaging to assess response was done 4 weeks after completing radiation and the results were were; 2 CR, 11 PR, 14 SD, 2 PD. Surgery was performed 6-8 weeks after completing radiation. Twenty six (81%) underwent planned resection, 2 had PD, 3 declined surgery and 1 had significant decline in PS. Twenty two out of Twenty six patients undergoing surgery had a R0 resection (80%). Grade-III/IV toxicities with the neo-adjuvant treatments were seen in 41% and 7 % of the pts., respectively. No thirty day post-op mortality, pancreatic leaks or re-operations were observed. The median PFS among all patients was 11.7 months, 2 yr OS 49% and median OS was 27.6 months, compared to 23.4 months, 65% and median OS not reached, in patients who underwent surgical resection. Conclusions: Nab-Paclitaxel and Gemcitabine followed by Capecitabine and radiation is an effective neo-adjuvant treatment strategy with acceptable toxicity-profile for patients with BR pancreatic cancer.
A study of preoperative FOLFIRINOX in potentially curable pancreatic cancer.
Authors: Javan Hamed , Niazi Tamim , Vanounou Tsafrir , Pelletier Jean-Sebastien , Dalfen Richard , Lecavalier-Barsoum Magali , Batist Gerald , Kavan Petr 
Published: February 2020

719 Background: Although Folfirinox (FFX) prolonged survival in metastatic and adjuvant setting, the role of preoperative FFX is still controversial. Our aim is to evaluate how surgery after neoadjuvant FFX with or without radiotherapy (RT) affects the clinical outcome in these patients. Methods: This is a single arm, open-label, phase 2 prospective study. Based on resectability criteria (NCCN-V.1.2017), patients prospectively were divided into 3 groups of resectable, borderline resectable (BR), locally advanced (LA). Patients received 6 cycles of preoperative FFX. Patients with adequate response, underwent resection. Continuation of chemotherapy or radiation was given to the patients who were deemed unresectable after 6 cycles. Primary objective is time to progression (TTP), and secondary objectives are safety, R0/R1 resection rate, response rate (RR) and overall survival (OS). Results: 20 consecutive patients with pancreatic adenocarcinoma enrolled. The frequency of each group was 4, 8, 8 patients, respectively. Median age was 64 years old (range, 49-78). 45% of patients had primary tumor in head or uncinate process. 25% of cases presented with normal CA 19-9 value. 85% (17/20) of patients completed the preoperative treatment. Folfirinox was given within median of 11.5 weeks (range, 8-17) and median of 6 cycles (range, 1-7). Median relative dose intensity (RDI) was 85.89%. Grade III-IV (G3+4) adverse event (CTCAE-4.03) observed in 47.4% (9/19). RR (RECIST) was 89% (16/18). Best response was partial response (PR) and stable disease (SD) with 22.2% (4/18) and 66.7% (12/18). Resection rate was 64.3% (9/14, 1 case scheduled for resection). R0 and negative lymph node (LN) achieved in 87.50% (7/8) and 62.50% (5/8) of patients. Complete pathological response (cPR) was seen in one patient 12.5% (1/8) who preoperatively reported as SD. Patients TTP and OS will be reported during the meeting. Conclusions: Preoperative FFX was associated with high clinical and pathological response rate translating in high resection rate in majority of BRPC and LAPC, and appears to be a safe treatment strategy. Patients received higher FFX dose intensity than it was reported in adjuvant setting. However, these results need to be assessed in a randomized trial. Clinical trial information: NCT03167112.
The impact of pancreatic cancer resection in the era of effective systemic treatment.
Authors: Lawrence Yaacov Richard , Margalit Ofer , Jacobson Galia , Hamer Liat , Amit Uri , Halpern Naama , Shmueli Einat Shacham , Boursi Ben , Goldes Yuri , Azoulay Daniel , Golan Talia , Symon Zvi 
Published: February 2020

722 Background: Surgical resection is the only curative modality in pancreatic cancer, yet the vast majority of patients undergoing surgery succumb of their disease. No randomized studies have been performed to assess the survival impact of the procedure. We hypothesized that in the era of effective systemic treatments, the survival advantage of surgical resection would be lessened. Methods: A meta-analysis of published phase III clinical trials in pancreatic cancer in both the post resection adjuvant setting and the locally advanced metastatic setting, based upon indirect aggregate data. Data was stratified based upon the systemic agents used. Patients from trials arms for which there were not complementary data sets with/without surgical resection were excluded. Primary endpoint was 3 year overall survival (OS). Results: Trials were published between 1997 and 2018. A total of 2722 patients were included in the data analysis, of whom 1645 underwent tumor resection and 814 were metastatic. Median follow-up was 40 months. Analyses were performed of five systemic options with / without tumor resection. Across the trials averaged 3 yr OS was 0%, 0.8%, 0%, and 3.8% for 5FU, gemcitabine, gemcitabine + capecitabine, & FOLFIRINOX respectively; and 18.1%, 30.0%, 37.9%, 42.5%, and 62.5% for the same systemic treatments delivered following surgical resection. Hence the additive impact of surgical resection on absolute 3 yr OS was only 18.1% in the absence of systemic treatment, but 30.0%, 37.1%, 42.5% and 58.8% in the presence of 5FU, gemcitabine, gemcitabine + capecitabine, FOLFIRINOX respectively. Conclusions: Within the limitations of this analysis, it appears that our hypothesis was incorrect, and that the opposite is true. The introduction of effective systemic therapies has greatly increased the impact of pancreatic surgery on long-term survival in pancreatic cancer. Consequently, every effort should be made to bring patients to curative resection.
Homologous recombination deficiency (HRD) scoring in pancreatic ductal adenocarcinoma (PDAC) and response to chemotherapy.
Authors: O'Kane Grainne M. , Denroche Rob , Picardo Sarah Louise , Zhang Amy , Holter Spring , Grant Robert C. , Allen Michael , Wang Yifan , Dodd Anna , Ramotar Stephanie , Hutchinson Shawn , Tehfe Mustapha , Biagi James Joseph , Wilson Julie , Notta Faiyaz , Fischer Sandra , Zogopoulos George , Gallinger Steven , Knox Jennifer J. 
Published: February 2020

741 Background: Whole genome sequencing (WGS) can reveal patterns of substitution base signatures and structural variation consistent with tumours deficient in homologous recombination repair. We evaluated the published HRDetect score and a novel HRD hallmark score (HS) in patients receiving combination chemotherapy (cCT) on the COMPASS trial for advanced PDAC. Methods: The HRD-HS incorporates 10 genomic characteristics of HRD-PDAC with a score ≥ 4 defining HRD. HRD-HS and an HRDetect score ≥0.7 were applied to WGS data and overall survival (OS) and response (ORR) evaluated. Sensitivity and specificity were ascertained. Results: As of 05/19, 205 eligible patients (pts) were enrolled and 186 received cCT including modified FOLFIRINOX n = 108 (58%) or cisplatin/gemcitabine n = 2 (1%) and gemcitabine/nab-paclitaxel n = 76 (41%). HRD-HS had a sensitivity of 87.5% and specificity of 100% in detecting HRD-PDAC. In contrast, HRDetect (≥0.7) had sensitivity of 51.9% and specificity of 100%; sensitivity increased to 73.7% when using a cutoff score of ≥0.99. 23/186 (12%) pts were classified as HRdetecthi and median OS was 15.3months (mo) vs 8.7mo in HRDetectlo pts (HR 0.44 95% CI 0.27-.70, p = 0.009). In platinum treated pts, median OS was 18.1mo (HRDetecthi) vs 9.3mo (HRDetectlo) (HR 0.38 95%CI 0.21-0.69, p = 0.02). HRD-HS predicted the longest median OS for platinum of 21.0mths. ORR in HRDetecthi was not different to HRDetectlo pts treated with cCT, however in those receiving platinum the ORR was 50% vs 19% respectively (p < 0.001). Of the false positives by HRDetect, 46% had a non-BRCA1 tandem duplicator phenotype (TDP). The TDP group comprised 8% of all patients enrolled. HRD-PDAC was caused by inactivation of BRCA1/2, PALB2, RAD51C and XRCC2; all germline variants were pathogenic. Pathogenic ATM and CHEK2 germline variants were present in 3 pts with evidence of a second somatic hit or LOH, none of these identified as HRD by either classifier nor considered a TDP. Conclusions: HRD-HS most correctly identified HRD-PDAC however the HRDetect score classifies additional patients sensitive to cCT, especially platinum. The TDP cohort may be responsive to DNA damaging agents warranting further evaluation. Clinical trial information: NCT02750657.