bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of the volume time index (VTI) ratio for patients with appendiceal cancer with peritoneal carcinomatosis treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).
Authors: Karpes Josh , Dotta Daniel , Fisher Oliver , Shamavonian Raphael , Alzahrani Nayef , Morris David L. 
Published: May 2019

e15704 Background: Completeness of cytoreduction score (CC-score) and tumour volume (as expressed by the peritoneal cancer index (PCI)) have been demonstrated as important post-operative prognostic factors in those patients with appendix cancer with peritoneal metastases undergoing CRS/HIPEC. A previous analysis included a pre-operative factor and demonstrated the tumour marker to volume index (CA19-9/PCI) in patients who had low grade appendiceal cancer with peritoneal metastases was an independent prognostic factor for overall survival (OS). This analysis aims to evaluate VTI as a prognostic factor in low- and high-grade appendix neoplasms with peritoneal dissemination managed with CRS/HIPEC. Methods: A retrospective cohort study of all patients diagnosed with appendiceal cancer with peritoneal dissemination managed with CRS/IPC from 1996 to 2017 was performed by analysing the survival effect of the ratio of tumour volume to the time between initial tumour resection and CRS/HIPEC. VTI was stratified into low versus high groups, and tumour grade was divided into low grade: diffuse peritoneal adenomucinosis (DPAM); and high grade: peritoneal mucinous carcinomatosis (PMCA). Results: Two hundred and sixty-four patients were included. For both DPAM and PMCA, there was no statistically significant difference in overall survival between patients with a low versus high VTI. For both low and high VTI in DPAM, the median survival was not reached, p= 0.586. For PMCA, those with a low VTI had an overall survival of 63 months (95%CI 48-NR), versus those with a high VTI 69 months (95%CI 45-NR), p= 0.97. There was no statistically significant difference in the median recurrence free survival (RFS) between low and high VTI for both DPAM and PMCA. Conclusions: The volume to time ratio for appendix cancer with peritoneal dissemination was not an independent prognostic indicator for overall survival in patients undergoing CRS/HIPEC, suggesting that this index is not a valuable pre-operative planning tool.
Real-world assessment of healthcare costs for patients with metastatic pancreatic cancer following first-line chemotherapy initiation.
Authors: Bullock Andrea J. , Rowan Christopher G , Hill Nina , Yeganegi Homa , Chiorean E. Gabriela 
Published: May 2019

e15710 Background: Nab-paclitaxel-gemcitabine (AG) and FOLFIRINOX (FFX) are commonly used regimens for the treatment of metastatic pancreatic cancer (mPDA). This descriptive study aimed to report total healthcare costs following first line (1L) exposure to AG/FFX among patients with mPDA. Methods: Retrospective cohorts of 1L AG and FFX initiators with mPDA were constructed from the MarketScan database (study period 2014-2017). The index date was the date of 1L AG or FFX initiation. Included patients had continuous insurance enrollment. Total healthcare costs (outpatient, inpatient, emergency department, chemotherapy, pharmacy) were assessed at 0-1, 0-3, 0-6, and 0-12 months post-index among patients who remained uncensored (using the last claim date) through the last month of each follow-up interval. Results: 2199 patients initiated AG (N=1352) or FFX (N=847) as their 1L regimen. Compared with AG initiators, FFX patients were younger (59 vs 63 years) and had better baseline health status (FFX/AG): diabetes 43%/57%; cerebrovascular disease 21%/27%. Median time to censoring was 5.4 (AG) and 7.2 (FFX) months. Median treatment duration was 2.1 (AG) and 2.3 (FFX) months. FFX costs were higher than AG costs during each follow-up interval, with the cost differential increasing over time (Table). Conclusions: Higher total healthcare costs were observed for patients with mPDA who initiated 1L FFX compared with 1L AG. Further research using comparative methodology is warranted to fully elucidate these findings and understand cost drivers. [Table: see text]
Sequential assessments of KRAS-mutated circulating tumor DNA in longitudinal monitoring enable the prediction of prognosis and therapeutic responses in patients with pancreatic cancer.
Authors: Watanabe Fumiaki , Suzuki Koichi , Tamaki Sawako , Ishikawa Hideki , Kakizawa Nao , Noda Hiroshi , Rikiyama Toshiki 
Published: May 2019

e15712 Background: Liquid biopsy enables the detection of circulating tumor DNA (ctDNA) levels, including KRAS-mutated ctDNA, which is considered a predictive biomarker for pancreatic cancer. This study aimed to evaluate the significance of sequential KRAS ctDNA assessments in longitudinal monitoring. Methods: A total of 422 blood samples were collected from 78 patients undergoing treatments for localized and metastatic pancreatic ductal adenocarcinoma. KRAS ctDNA levels was determined by droplet digital polymerase chain reaction. Longitudinal monitoring of KRAS ctDNA was performed to assess its significance for predicting recurrence and prognosis and evaluating therapeutic responses to chemotherapy. Results: In 39 patients who underwent surgery for potentially resectable tumors, sequential assessments of KRAS ctDNA in longitudinal monitoring was significantly associated with prognosis ( P < 0.001). In 39 patients who did not undergo surgery, sequential assessments of KRAS ctDNA was a predictive factor for prognosis ( P = 0.005). Multivariate analysis revealed that detection of KRAS ctDNA in longitudinal monitoring was the only independent prognostic factor regardless of tumor resection ( P< 0.001). Longitudinal monitoring revealed the significance of sequential assessments of KRAS ctDNA within a short period. The presence of KRAS ctDNA in sequential assessments within 1 year after surgery showed significant association with prognosis irrespective of recurrence ( P< 0.001). The presence of KRAS ctDNA in sequential assessments within 6 months was significantly correlated with therapeutic responses in the first line chemotherapy ( P< 0.001). Conclusions: Our study showed for the first time that sequential assessments of KRAS ctDNA levels within a short period enabled the prediction of prognosis and therapeutic response in patients with pancreatic cancer.
Serum microRNA signatures for the detection of pancreatobiliary cancer.
Authors: Mitsunaga Shuichi , Nomura Shogo , Hara Kazuo , Takayama Yukiko , Ueno Makoto , Hanada Keiji , Miki Ikuya , Takahashi Shinichiro , Kuwahara Takamichi , Nomoto Tomohiro , Sudo Tamotsu , Myomoto Akira , Sudo Hiroko , Takizawa Satoko , Kojima Motohiro 
Published: May 2019

e15718 Background: The diagnostic value of serum microRNAs (miRNA) in a highly sensitive microarray for pancreatobiliary cancer (PBca) has been demonstrated. This study attempted to build and validate a signature comprised of multiple serum miRNA markers for discriminating PBca from healthy controls. Methods: A multicenter prospective study on the diagnostic performance of serum miRNAs was conducted. The patients (pts) with treatment-naïve PBca and healthy participants aged ≥60 years were enrolled. Clinical data and sera were collected. Target population was randomly divided to training or validation cohort with an allocation ratio of 2:1. Twenty-nine serum miRNA markers on the microarray data were analyzed. Using any combinations of the markers, a Fisher’s linear discriminant analysis was performed, and the resulting sensitivity, specificity and AUC of ROC curve to discriminate PBca from healthy controls were calculated for each combination. Marker combinations with a sensitivity/specificity (SN/SP) of ≥80%/90% and high AUC in comparison with AUC of CA19-9 were defined as the diagnostic miRNA signature, which were selected in the training cohort. Next, the signatures were screened out which showed a good reproducibility in the validation cohort. As an independent external cohort, PBca pts and healthy with pooled frozen sera were enrolled and the identified miRNA signatures were further validated. Results: Total of 546 participants (80 healthy and 223 PBca in training set, 40 healthy and 104 PBca in validation set, 49 healthy and 50 PBca in external validation set) were analyzed in this study. Four serum miRNA combinations were identified as the diagnostic miRNA signature. In the training set, four miRNA signatures, consisted of 10 miRNAs, were developed. For the best-performed miRNA signature, the SN/SP and AUC in the validation and external validation cohorts were 84/90% and 0.95 (CA19-9: 73/95% and 0.88) and 84/90% and 0.93 (CA19-9: 80/94% and 0.87), respectively. Conclusions: The diagnostic serum miRNA signatures for PBca were identified in this study.
Adjuvant FOLFOX + nab-paclitaxel (FOLFOX-A)for pancreatic cancer, BrUOG 278: A Brown University oncology research group phase II study.
Authors: Safran Howard , Charpentier Kevin , Breakstone Rimini , Vatkevich John , Hamel Celine , Kolvek Taylor , Kastura Michaela , Bartley Carolyn , Baekey John , Robison Jordan , Beard Rachel , Leonard Kara Lynne , Rossiter Rachael , Rosati Kayla 
Published: May 2019

e15733 Background: Adjuvant FOLFIRINOX increases survival in pancreatic cancer but is associated with significant toxicity. The Brown University Oncology Research Group (BrUOG) developed the FOLFOX-A regimen in a phase I study in advanced pancreatic cancer (Am J Clin Oncol, 2016). Phase II studies (BrUOG 292 and BrUOG 318) have shown substantial activity in patients with metastatic and locally advanced disease. Highly active regimens have the potential to improve survival in the adjuvant setting. The primary objective of BrUOG 295 was to determine the feasibility of administering 10 cycles of FOLFOX-A. Secondary objectives were toxicity and disease free survival. Methods: Patients received oxaliplatin, 85mg/m2 day 1, nab-paclitaxel, 150mg/m2 and leucovorin 400mg/m2 day 1 and fluorouracil 2400mg/m2 by continuous IV infusion over 46 hours. Myeloid growth factor support was optional. Cycles were repeated every 14 days for up to 10. Oxaliplatin was dose reduced to 68mg/m2 for grade 2 neurotoxicity. CTCAE version 4 toxicity scales were utilized. Results: The study reached its initial accrual goal of 25 patients. The median age was 60 (43-69). Twenty-one patients were node +. Twelve of the first 20 patients have received 10 cycles of FOLFOX-A and 17 of the first 20 patients received > 8 cycles. The most common grade >3 toxicities were neutropenia grade 3 (N = 3), grade 4 (N = 3) and fatigue grade 3 (n = 13). One patient had grade 3 neuropathy. Conclusions: Adjuvant FOLFOX-A is well tolerated with low incidences of grade 3 neuropathy and gastrointestinal toxicity. Toxicity, feasibility and disease free survival will be updated at the May 2019 BrUOG DSMB meeting. Clinical trial information: NCT02022033.
Relapse-free survival (RFS) after surgical resection to predict survival after relapse (SAR) and overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDA).
Authors: Rodriguez-Pascual Jesus , Alvarez-Gallego Rafael , Munoz Cesar , Ugidos Lisardo , Sanz Enrique , Ceniceros Lucia , Rivas Maria , Torres Esther , Cardenas Jose M , Cubillo Gracián Antonio 
Published: May 2019

e15735 Background: We aimed to evaluate the clinical relevance of RFS after local PDA resection as a prognostic factor in terms of SAR and OS. Methods: Patients diagnosed with local PDA who had undergone surgical resection in 4 hospitals from Spain were identified. Disease location, demographic, pathologic, treatment during recurrence and mortality information was retrospectively collected. RFS was measured from date of surgery until recurrence and censored at death or last follow-up. SAR was measured from relapse, until death or last follow-up. We defined patients presenting an RFS value of 6 months or more, or less than 6 months as High-RFS and Low-RFS respectively. Results: Of 93 patients with resected PDA, 51 (54.8%) were male and 42 (45.2%) female. The median age was 65.2 years. 62 (66.7%) tumors were localized in the head. There were 5 (5.4%), 17 (18.3%) and 69 (74.1%) stage I, II and III respectively. 53 (57%) patients had undergone cephalic (Whipple), 20 (21.5%) distal and 20 (21,5%) total pancreatectomy. 48 (51.6%) patients received radiotherapy and 86 (92.5%) received chemotherapy in the neoadjuvant and/or adjuvant setting. Median RFS was 12.3 months. In the metastatic setting, the most frequent chemotherapy combination was gemcitabine plus nab-paclitaxel. 43(46,2%) of patients received second line chemotherapy. Median OS and median SAR were 25,9 and 10,1 months respectively. Kaplan-Meier survival analysis showed that PDA cancer patients with Low-RFS have a poorer clinical outcome than those with High-RFS (median OS 48.26 months, CI 95% 39,3-57,1 for High-RFS; 19.2 months CI 95% 15.7-22-8 for Low-RFS; p = 0.0001). On multivariate Cox regression analysis, age, initial stage I-II, adjuvant chemotherapy utilization and High-RFS were independent prognostic factors for OS and SAR rate. Conclusions: RFS was strongly correlated and discriminated PDA patients with better SAR and OS from the poorer prognosis patients in the ulterior metastatic setting. Prospective studies are needed to confirm this finding.
Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution.
Authors: Hosein Abdel Nasser , Huang Huocong , Wang Zhaoning , Parmar Kamalpreet , Du Wenting , Huang Jonathan , Maitra Anirban , Olson Eric , Verma Udit , Brekken Rolf A. 
Published: May 2019

e15739 Background: Pancreatic ductal adenocarcinoma (PDA) is a major cause of cancer-related death with limited therapeutic options available. This highlights the need for improved understanding of the biology of PDA progression. The progression of PDA is a highly complex and dynamic process featuring changes in cancer cells and stromal cells; however, a comprehensive characterization of PDA cancer cell and stromal cell heterogeneity during disease progression is lacking. In this study, we aimed to profile cell populations and understand their phenotypic changes during PDA progression. Methods: We employed single-cell RNA sequencing technology to agnostically profile cell heterogeneity during different stages of PDA progression in genetically engineered mouse models. Results: Our data indicate that an epithelial-to-mesenchymal transition of cancer cells accompanies tumor progression. We also found distinct populations of macrophages with increasing inflammatory features during PDA progression. In addition, we noted the existence of three distinct molecular subtypes of fibroblasts in the normal mouse pancreas, which ultimately gave rise to two distinct populations of fibroblasts in advanced PDA, supporting recent reports on intratumoral fibroblast heterogeneity. Our data also suggest that cancer cells and fibroblasts are dynamically regulated by epigenetic mechanisms. Conclusions: This study systematically outlines the landscape of cellular heterogeneity during the progression of PDA. It strongly improves our understanding of the PDA biology and has the potential to aid in the development of therapeutic strategies against specific cell populations of the disease.
Nab-paclitaxel/S-1(AS) versus nab-paclitaxel/gemcitabine(AG) for first-line chemotherapy in advanced pancreatic ductal adenocarcinoma (aPDAC): A retrospective analysis of efficacy and safety.
Authors: Zong Yuan , Peng Zhi , Lu Ming , Wang Xicheng , Zhou Jun , Shen Lin 
Published: May 2019

e15743 Background: AG significantly improved PFS and OS compared with gemcitabine monotherapy in patients (pts) with metastatic PDAC, but the confirmed ORR was limited to 23% with increased grade 3 or 4 myelosuppression. In GEST and JASPAC01 studies, S-1 showed non-inferior or superior activity to gemcitabine in advanced and postoperative PDAC. S-1 also developed less hematologic adverse events especially in neutropenia and was a convenient oral alternative. Two single-arm phase II trials in China demonstrated high ORR of 50.0-53.1% with AS. We investigated the efficacy and safety of first-line chemotherapy with AS versus AG in pts with aPDAC. Methods: A retrospective review was conducted of aPDAC pts treated with first-line AS and AG in GI dpt. Of PUCH between 11/2013 and 12/2018. Pts received 125mg/m2 nab-paclitaxel intravenously (IV) on day1, and 80-100mg S-1 orally per day on day1-7 every two weeks in AS cohort, while pts received 125mg/m2 nab-paclitaxel IV on day1,8, and 1000mg/m2 gemcitabine IV on day1,8 every three weeks in AG cohort. ORR, ORR of primary lesion, DCR, PFS, OS and safety were analysed between two cohorts. Survival outcomes were evaluated by Kaplan-Meier method and compared with the log-rank test. A Cox proportional hazard model was made to determine independent predictors of survival. Results: A total of 70 pts (45 in AS cohort, 25 in AG cohort) with locally advanced (4%) and metastatic (96%) PDACs were identified. 75% were male and the median age was 65(range 36-72). Among intention-to-treat population, the ORR and DCR were 40.0% vs 32.0% (p = 0.70) and 75.6% vs 64.0% (p = 0.57) in AS and AG cohort, respectively. The ORR of primary lesion was 31.1% with AS vs 20.0% with AG (p = 0.73). With the median follow-up of 9.8 months(range 2.3-22.2), the median PFS and OS were 4.7m vs 6.7m (HR, 1.2; 95% CI, 0.6 to 2.4; p = 0.62) and 10.3m vs 11.3m (HR, 0.9; 95% CI, 0.5 to 1.8; p = 0.78) in AS and AG cohort, respectively. Grade 3/4 toxicities occurred in 31.1% AS vs 36.0% AG (p = 0.59). Most G3/4 toxicities were: leukopenia/neutropenia (26.7% vs 20.0%), febrile neutropenia (2.2% vs 8.0%), thrombocytopenia (0 vs 12%), fatigue (4.4% vs 12%), peripheral neuropathy (0 vs 8.0%). In multivariate analysis, liver metastasis was the only independent predictor of poor OS (HR 0.3, 95%CI 0.1-0.8, p = 0.014). Conclusions: AS was a comparable and convenient alternative with manageable toxicities in aPDAC. There was a trend towards improved ORR of primary lesion compared with AG.
Combination therapy of dendritic cell vaccination plus chemotherapy in pancreatic cancer.
Authors: Chiriva-Internati Maurizio , Mirandola Leonardo , Bresalier Robert , Dahlbeck Scott , Figueroa Jose A. , Nguyen Diane Duyen Thuy 
Published: May 2019

e15748 Background: Pancreatic cancer is one of the world’s deadliest malignancies with an average 5-year survival rate of only 9%. Fortunately, immunotherapy is providing encouraging results for treatment of this historically resistant malignancy. Kiromic Biopharma is performing a phase I/II dendritic cell vaccine trial for progressive solid malignancies. We present here a notable response to metastatic pancreatic cancer. Methods: The patient is a 73-year-old male with the history of a locally advanced pancreatic cancer treated initially with gemcitabine, concurrent 5FU and radiation therapy, and consolidation 5FU, followed by surgical resection in 2009 . Although the patient did well exceeding typical survival curves, the patient’s cancer became metastatic, requiring multiple lines of chemotherapy including FOLFIRINOX, gemzar and abraxane, and most recently Onivyde and leucovorin/5FU in February - August, 2017 for progressive liver and lung metastases. The patient was then enrolled onto Kiromic Biopharma’s DC vaccination trial in March, 2018. Results: He subsequently received 6 ID autologous dendritic cell vaccinations over 12 weeks, demonstrating a tumor antigen specific immunogenic response by IFN-gamma immunoassay. Total tumor burden (TTB) prior to clinical trial enrollment at the sites of metastatic disease was 2,221mm2, and after completion of the DC vaccination protocol in May, 2018, the TTB increased to 4,466mm2 in June, 2018 (not considered to be pseudo-progression due to a corresponding increase in tumor biomarkers). The patient then received a repeat course of Onivyde and leucovorin/5FU on 8-3-18, completing that course of therapy on 9-14-18, with subsequent TTB decreasing to 2,986 mm2. Conclusions: The sequential combination of dendritic cell vaccine and chemotherapy resulted in a substantial response with a recession in metastatic tumor burden. A CT scan was obtained just 6 days after the 5 week course of Onivyde was completed, and given the optimal immunotherapy window after the DC vaccination, and the repeat of the same chemotherapy regimen, it is unlikely that chemotherapy alone led to such a rapid decrease in the TTB. Metastatic sites were likely populated by chemo resistant clones that survived the August 2017 administration of the Onivyde regimen. Thus, chemo alone would be unlikely to act so quickly. We hypothesize that there was synergistic activity between the DC immunotherapy and the Onivyde/5FU regimen, accounting for the decrease in TTB between May and September, 2018. Clinical trial information: NCT02705703.
Tolerability and safety of a replication-competent adenovirus-mediated double suicide gene therapy (Ad5-yCD/mutTK(SR39)rep-ADP) with chemotherapy in locally advanced pancreatic cancer: Phase 1 trial.
Authors: Lee Jong-Chan , Shin Dong Woo , Yang Se Yeol , Kim Min Jae , Jung Jae Hyup , Kang Jingu , Kim Jaihwan , Hwang Jin-Hyeok 
Published: May 2019

e15761 Background: Up to 35% of pancreatic cancers are considered ‘locally advanced’ (LAPC) at the time of diagnosis. Replication-competent adenovirus-mediated double suicide gene therapy (Ad5-yCD/mutTK(SR39)rep-ADP) showed an anti-cancer effect in prostatic cancer patients in previous studies. We aimed to investigate tolerability and safety of Ad5-yCD/mutTK(SR39)rep-ADP in combination with gemcitabine in patients with LAPC. Methods: In this single-center, open label, dose-escalation phase I trial, we recruited adult patients (≥18 years) with newly diagnosed LAPC. Patients with histologically confirmed pancreatic ductal adenocarcinoma with good performance were enrolled. We injected Ad5-yCD/mutTK(SR39)rep-ADP into pancreatic mass with EUS-FNB needle in combination with oral 5-fluorocytosine 500mg qd, oral valgancyclovir 450mg qd, and standard gemcitabine (1000mg/m2, day 1-8-15 infusion every 4 weeks). In the three-stage dose-escalation scheme with traditional 3+3 design, the dose of Ad5-yCD/mutTK(SR39)rep-ADP in each cohort was 1x1011, 2x1011, and 1x1012 vp/mL, respectively. Every patient has been evaluated adenovirus-induced toxicity in 8 weeks and tumor response in 12 weeks. The primary aim is to establish the maximum tolerated dose (MTD) of Ad5-yCD/mutTK(SR39)rep-ADP, as assessed by dose-limiting toxicities (DLT). Results: From 2016 to 2018, we enrolled 11 patients and analyzed nine patients for the final cohort. Two were dropped out by withdrawal of consents. In the first evaluation period (8 weeks), any of patients did not experience dose-related serious adverse event. Only one patients of in 3rd cohort experienced transient grade II fever. In the second evaluation period (12 weeks), two patients showed partial response (PR) and seven showed stable disease (SD). Adenovirus DNA fragments disappeared in median 50 days (range 20 – 139). After the gemcitabine periods, five patients received 2nd-line chemotherapy with FOLFIRINOX, and overall survival was median 14.9 months (range 8.9 – 21.9). Conclusions: In this phase I trial, Ad5-yCD/mutTK(SR39)rep-ADP has been well-tolerated without dose-related severe adverse events, and no MTD reached in locally advanced pancreatic cancer. Phase II clinical trial is needed for evaluating clinical efficacy. Clinical trial information: NCT02894944.