scholarly journals Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4131
Author(s):  
Alice Usai ◽  
Gregorio Di Franco ◽  
Margherita Piccardi ◽  
Perla Cateni ◽  
Luca Emanuele Pollina ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Recurrence Rate ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Treatment Modalities ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
Tumor Tissues ◽  
Trial Testing ◽  
Cancer Recurrence Rate

It is increasingly evident the necessity of new predictive tools for the treatment of pancreatic ductal adenocarcinoma in a personalized manner. We present a co-clinical trial testing the predictiveness of zPDX (zebrafish patient-derived xenograft) for assessing if patients could benefit from a therapeutic strategy (ClinicalTrials.gov: XenoZ, NCT03668418). zPDX are generated xenografting tumor tissues in zebrafish embryos. zPDX were exposed to chemotherapy regimens commonly used. We considered a zPDX a responder (R) when a decrease ≥50% in the relative tumor area was reported; otherwise, we considered them a non-responder (NR). Patients were classified as Responder if their own zPDX was classified as an R for the chemotherapy scheme she/he received an adjuvant treatment; otherwise, we considered them a Non-Responder. We compared the cancer recurrence rate at 1 year after surgery and the disease-free survival (DFS) of patients of both groups. We reported a statistically significant higher recurrence rate in the Non-Responder group: 66.7% vs. 14.3% (p = 0.036), anticipating relapse/no relapse within 1 year after surgery in 12/16 patients. The mean DFS was longer in the R-group than the NR-group, even if not statistically significant: 19.2 months vs. 12.7 months, (p = 0.123). The proposed strategy could potentially improve preclinical evaluation of treatment modalities and may enable prospective therapeutic selection in everyday clinical practice.

scholarly journals Developing a preoperative serum metabolome-based recurrence-predicting nomogram for patients with resected pancreatic ductal adenocarcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Seoung Yoon Rho ◽  
Sang-Guk Lee ◽  
Minsu Park ◽  
Jinae Lee ◽  
Sung Hwan Lee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Area Under The Curve ◽  
Pancreatic Head ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Early Recurrence ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
Preoperative Serum

AbstractWe investigated the potential application of preoperative serum metabolomes in predicting recurrence in patients with resected pancreatic cancer. From November 2012 to June 2014, patients who underwent potentially curative pancreatectomy for pancreatic ductal adenocarcinoma were examined. Among 57 patients, 32 were men; 42 had pancreatic head cancers. The 57 patients could be clearly categorized into two main clusters using 178 preoperative serum metabolomes. Patients within cluster 2 showed earlier tumor recurrence, compared with those within cluster 1 (p = 0.034). A nomogram was developed for predicting the probability of early disease-free survival in patients with resected pancreatic cancer. Preoperative cancer antigen (CA) 19–9 levels and serum metabolomes PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful preoperative clinical variables with which to predict 6-month and 1-year cancer recurrence-free survival after radical pancreatectomy, with a Harrell’s concordance index of 0.823 (95% CI: 0.750–0.891) and integrated area under the curve of 0.816 (95% CI: 0.736–0.893). Patients with resected pancreatic cancer could be categorized according to their different metabolomes to predict early cancer recurrence. Preoperative detectable parameters, serum CA 19–9, PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful predictors of early recurrence of pancreatic cancer.

scholarly journals Prognostic factors for disease-free survival in patients with pancreatic ductal adenocarcinoma after surgery

2019 ◽  
Vol 2 (1) ◽  
pp. 22-27
Author(s):  
Xiaodong Tian ◽  
Jisong Li ◽  
Hongqiao Gao ◽  
Yan Zhuang ◽  
Yongsu Ma ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
Disease Free

scholarly journals Overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues predicts poor survival in pancreatic ductal adenocarcinoma

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Shu Dong ◽  
Fei Huang ◽  
Hao Zhang ◽  
Qiwen Chen
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Gene Expression Omnibus ◽  
Ductal Adenocarcinoma ◽  
Advanced Tumor Stage ◽  
Kaplan Meier ◽  
Advanced Tumor ◽  
Tumor Tissues

AbstractOverexpressed genes in tumors usually contributed to aggressiveness in pancreatic ductal adenocarcinoma (PDAC). Using Gene Expression Omnibus (GEO) profiles including GSE46234, GSE71989, and GSE107610, we detected overexpressed genes in tumors with R program, which were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO), and Reactome pathway databases. Then, we performed a survival analysis of enriched genes based on TCGA profile. Our results revealed that high BUB1B, CCNA2, CDC20, and CDK1 expression in tumors was significantly associated with worse overall survival (OS) (Log rank P=0.00338, P=0.0447, P=0.00965, and P=0.00479, respectively), which was validated using a Kaplan–Meier plotter with a median cutoff (Log rank P=0.028, P=0.0035, P=0.039, and P=0.0033, respectively). Moreover, overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues was significantly associated with disease-free survival (DFS) in PDAC patients (Log rank P=0.00565, P=0.0357, P=0.00104, and P=0.00121, respectively). BUB1B, CCNA2, CDC20, and CDK1 were significantly overexpressed in deceased PDAC patients (all P<0.01) and in patients with recurrence/disease progression (all P<0.05). In addition, PDAC patients with neoplasms of histologic grade G3-4 had significantly higher BUB1B, CCNA2 and CDC20 levels (all P<0.05). In conclusion, the up-regulation of BUB1B, CCNA2, CDC20, CDK1, and WEE1 in tumor tissues are associated with worse OS and DFS in PDAC and is correlated with advanced tumor stage and tumor development.

scholarly journals Effect of non-alcoholic liver disease on recurrence rate and liver regeneration after liver resection for colorectal liver metastases

2017 ◽  
Vol 24 (3) ◽  
pp. 233 ◽  
Author(s):  
N.W. Molla ◽  
M.M. Hassanain ◽  
Z. Fadel ◽  
L.M. Boucher ◽  
A. Madkhali ◽  
...  
Keyword(s):  
Liver Disease ◽  
Recurrence Rate ◽  
Transforming Growth Factor ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Hepatic Disease ◽  
Survival Duration ◽  
Free Survival ◽  
Computed Tomography Images ◽  
Disease Free

Background Resection of metastases is the only potential cure for patients with liver metastasis from colorectal cancer (crc-lm). But despite an improved overall 5-year survival, the recurrence rate is still as high as 60%. Nonalcoholic fatty liver disease (nafld) can decrease the liver’s capacity to regenerate after resection and might also affect cancer recurrence, potentially by elevating transforming growth factor β, levels of specific metalloproteinases, and oxidative stress. The objective of the present work was to determine the effect of the histologic features of nafld on cancer recurrence and liver regeneration.Methods This retrospective analysis considered 60 patients who underwent an R0 hepatectomy for crc-lm. Volumetric analysis of the liver was calculated using axial view, portovenous phase, 2.5 mm thickness, multiphasic computed tomography images taken before and after surgery. The histologic features of nafld (steatosis, inflammation, and ballooning) were scored using the nafld activity score, and the degree of fibrosis was determined.Results The hepatic recurrence rate was 38.33%. Median overall survival duration was 56 months. Median diseasefree survival duration was 14 months, and median hepatic disease-free survival duration was 56 months. Multivariate analysis revealed significant correlations of hepatic disease-free survival with hepatocyte ballooning (p = 0.0009), lesion diameter (p = 0.014), and synchronous disease (p = 0.006). Univariate and multivariate analyses did not reveal any correlation with degree of steatosis or recurrence rate.Conclusions This study reveals an important potential negative effect of hepatocyte ballooning on hepatic diseasefree survival.

scholarly journals Clinical Outcome of RAMPS for Left-Sided Pancreatic Ductal Adenocarcinoma: A Comparison of Anterior RAMPS Versus Posterior RAMPS for Patients without Periadrenal Infiltration

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1291
Author(s):  
Jaewoo Kwon ◽  
Yejong Park ◽  
Eunsung Jun ◽  
Woohyung Lee ◽  
Ki-Byung Song ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Survival Data ◽  
Survival Rates ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Ductal Adenocarcinoma ◽  
Perioperative Outcomes ◽  
Free Survival ◽  
R1 Resection ◽  
Radical Antegrade Modular Pancreatosplenectomy

Radical antegrade modular pancreatosplenectomy (RAMPS) is considered an effective procedure for left-sided pancreatic ductal adenocarcinoma (PDAC). However, whether there are differences in perioperative outcomes, pathologies, or survival outcomes between anterior RAMPS (aRAMPS) and posterior RAMPS (pRAMPS) has not been reported previously. We retrospectively reviewed and compared the demographic, perioperative, histopathologic, and survival data of patients who underwent aRAMPS or pRAMPS for PDAC. We also compared these two groups among patients without periadrenal infiltration or adrenal invasion. A total of 112 aRAMPS patients and 224 pRAMPS patients were evaluated. Periadrenal infiltration, neoadjuvant treatment, and concurrent vessel resection were more prevalent in the pRAMPS group. After excluding patients with periadrenal infiltration, 106 aRAMPS patients were compared with 157 pRAMPS patients. There were no significant differences between the aRAMPS and pRAMPS groups in the pathologic tumor size, resection margin, proportion of tangential margin in the R1 resection, and number of harvested lymph nodes. The median overall survival and disease-free survival also did not differ significantly between the two groups. We cautiously suggest that pRAMPS will not necessarily provide more beneficial histopathologic outcomes and survival rates for left-sided PDAC cases without periadrenal infiltration. If periadrenal infiltration is not suspected, aRAMPS alone should be sufficiently effective.

scholarly journals Adjuvant nab-paclitaxel plus gemcitabine versus gemcitabine in resected pancreatic ductal adenocarcinoma: A Chinese single institution experience.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 85-85
Author(s):  
Zhuzeng Yin ◽  
Rong Liu
Keyword(s):  
Adjuvant Chemotherapy ◽  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Group Versus ◽  
Disease Free Survival ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
R1 Resection ◽  
Grade 3 ◽  
Disease Free

85 Background: Adjuvant chemotherapy with gemcitabine (GEM) is standard care for resected pancreatic ductal adenocarcinoma (PDAC). Nab-paclitaxel plus gemcitabine (AG) vs gemcitabine (GEM) have shown better survival and tumor response with in advanced or metastatic PDAC. We aimed to determine the efficacy and safety of AG compared with GEM for resected PDAC. Methods: We retrospectively reviewed resectable PDAC patients (pts) who received AG or GEM as adjuvant chemotherapy from January 2013 to December 2016 at the Chinese PLA General Hospital, Bei Jing, China. Pts received nab-paclitaxel (125mg/m2) followed by GEM (1,000 mg/m2) on days 1, 8 every 3 weeks or GEM (1,000 mg/m2) alone on days 1, 8 every 3 weeks for 6 cycles unless disease progression or there was unacceptable level of adverse events. Disease free survival (DFS), overall survival (OS) and toxicity were analyzed. Results: Among 70 pts received AG or GEM as adjuvant chemotherapy, 10 pts were excluded due to the serious complication or R2 resection. The analysis was based on 30 pts in each group undergone complete macroscopic (R0 or R1) resection. Median DFS was 15.8 months (95% CI 13.1-18.5) in AG group (6 pts not arrived) compared with 12.2 months in GEM group (95% CI 9.6-14.8, P = 0.039, 3 pts not arrived). Median OS was 28.3 months (95% CI 21.9-34.6) in AG group (11 pts not arrived) as compared with 20.6 months in GEM group (95% CI 11.2-29.9, P= 0.028, 7 pts not arrived). The 2 years survival rate was 63.3% versus 43.3% in AG group versus GEM group. The most common adverse events of grade 3 or higher were leukopenia (32.3% in AG group vs. 20.7% in GEM group, P= 0.387), neutropenia (45.2% vs.31%, P= 0.298), G-CSF use (41.9% vs. 24.1%, P= 0.177), sensory peripheral neuropathy (51.6% vs. 24.1%, P= 0.036) and fatigue (3.2% vs. 3.4%, P= 0.737). Conclusions: Our results provide the evidence that the adjuvant combination of nab-paclitaxel plus gemcitabine significantly improved DFS and OS of resected PDAC.

scholarly journals Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Iranzu González-Borja ◽  
Emilia Alors-Pérez ◽  
Irene Amat ◽  
Laura Alonso ◽  
Cristina Viyuela-García ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Promoter Methylation ◽  
Neoadjuvant Treatment ◽  
Ring Finger ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
Entire Cohort

Checkpoint with forkhead-associated and ring finger domains (CHFR) has been proposed as a predictive and prognosis biomarker for different tumor types, but its role in pancreatic ductal adenocarcinoma (PDAC) remains unknown. The aim of this study was two-pronged: to review the role of CHFR in PDAC and evaluating CHFR as a potential predictive biomarker in this disease. For this purpose, we first explored the CHFR messenger (m)RNA expression and promoter methylation through the TCGA database. Secondly, the CHFR expression and promoter methylation were prospectively evaluated in a cohort of patients diagnosed with borderline (n = 19) or resectable (n = 16) PDAC by immunohistochemistry (IHC), methylation specific-PCR (MSP), and pyrosequencing. The results from the TCGA database showed significant differences in terms of progression-free survival (PFS) and overall survival (OS) based on the CHFR mRNA expression, which was likely independent from the promoter methylation. Importantly, our results showed that in primarily resected patients and also the entire cohort, a higher CHFR expression as indicated by the higher IHC staining intensity might identify patients with longer disease-free survival (DFS) and OS, respectively. Similarly, in the same cohorts, patients with lower methylation levels by pyrosequencing showed significantly longer OS than patients without this pattern. Both, the CHFR expression intensity and its promoter methylation were established as independent prognostic factors for PFS and OS in the entire cohort. In contrast, no significant differences were found between different methylation patterns for CHFR and the response to taxane-based neoadjuvant treatment. These results suggest the potential role of the higher expression of CHFR and the methylation pattern of its promoter as potential prognostic biomarkers in PDAC, thus warranting further comprehensive studies to extend and confirm our preliminary findings.

Tumor interface stability on CT imaging is an early marker of response to cytotoxic therapy in pancreatic ductal adenocarcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 284-284
Author(s):  
Christopher Wilke ◽  
Ahmed Amer ◽  
Dalia Elganainy ◽  
Priya Bhosale ◽  
Ott Le ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
Interface Stability ◽  
Visual Scoring

284 Background: There is currently no reliable biomarker for assessing the response to therapy of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated how changes in the tumor/parenchyma interface associate with response. Methods: We reviewed pre- and post-therapy scans of patients who received chemotherapy and/or chemoradiation for both localized and metastatic PDAC. We classified the interface between the PDAC tumor and surrounding pancreas parenchyma as stable (remains or becomes well-defined) or unstable (becomes poorly defined) using a novel visual scoring system and quantified changes in enhancement at this interface (Philips Intellispace Portal, quantitative European Association for the Study of Liver [qEASL]). Results: Three retrospective datasets were used to develop this method with consensus visual scoring performed by 3 radiologists. The first dataset included 99 patients with localized PDAC who received neoadjuvant chemoradiation. Patients who were classified as having a stable interface had significantly higher probability of achieving a complete or near-complete pathologic response (21% vs 0%, p = 0.01) and additionally demonstrated an improved median disease-free survival (DFS, 20.9 vs 7.9 mos., p < 0.01) and overall survival (OS, 47.7 vs 19.1 mos., p < 0.01). These results were validated in a separate dataset of 94 patients receiving protocol-based chemotherapy and chemoradiation (chemoRT cohort) and a cohort of 86 patients with stage IV disease. In both cohorts, a stable interface was associated with a significant improvement in progression free survival (PFS, Hazard Ratio [HR] 0.44, p = 0.01 for chemoRT and HR 0.70, p = 0.16 for stage IV) and OS (HR 0.42, p < 0.01 for chemoRT and HR 0.59, p = 0.05 for stage IV). Multivariate analyses for each cohort showed interface stability to be independently associated with both DFS/PFS and OS. Measurements obtained using qEASL were concordant with the visual scoring results. Conclusions: The interface stability of PDAC is an early readout of response to therapy. Integration of this imaging feature into clinical trials for localized and metastatic PDAC may aid in the future development of adaptive treatment strategies.

Adjuvant nab-paclitaxel plus gemcitabine versus gemcitabine in resected pancreatic ductal adenocarcinoma: A Chinese single institution.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15740-e15740
Author(s):  
Zhuzeng Yin ◽  
Rong Liu
Keyword(s):  
Adjuvant Chemotherapy ◽  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Group Versus ◽  
Disease Free Survival ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
R1 Resection ◽  
Grade 3 ◽  
Disease Free

e15740 Background: Adjuvant chemotherapy with gemcitabine (GEM) is standard care for resected pancreatic ductal adenocarcinoma (PDAC). Nab-paclitaxel plus gemcitabine (AG) vs gemcitabine (GEM) have shown better survival and tumor response with in advanced or metastatic PDAC. We aimed to determine the efficacy and safety of AG compared with GEM for resected PDAC. Methods: We retrospectively reviewed resectable PDAC patients (pts) who received AG or GEM as adjuvant chemotherapy from January 2013 to December 2016 at the Chinese PLA General Hospital, Bei Jing, China. Pts received nab-paclitaxel (125mg/m2) followed by GEM (1,000 mg/m2) on days 1, 8 every 3 weeks or GEM (1,000 mg/m2) alone on days 1, 8 every 3 weeks for 6 cycles unless disease progression or there was unacceptable level of adverse events. Disease free survival (DFS), overall survival (OS) and toxicity were analyzed. Results: Among 70 pts received AG or GEM as adjuvant chemotherapy, 10 pts were excluded due to the serious complication or R2 resection. The analysis was based on 30 pts in each group undergone complete macroscopic (R0 or R1) resection. Median DFS was 15.8 months (95% CI 13.1-18.5) in AG group (6 pts not arrived) compared with 12.2 months in GEM group (95% CI 9.6-14.8, P= 0.039, 3 pts not arrived). Median OS was 28.3 months (95% CI 21.9-34.6) in AG group (11 pts not arrived) as compared with 20.6 months in GEM group (95% CI 11.2-29.9, P= 0.028, 7 pts not arrived). The 2 years survival rate was 63.3% versus 43.3% in AG group versus GEM group. The most common adverse events of grade 3 or higher were leukopenia (32.3% in AG group vs. 20.7% in GEM group, P= 0.387), neutropenia (45.2% vs.31%, P= 0.298), G-CSF use (41.9% vs. 24.1%, P= 0.177), sensory peripheral neuropathy (51.6% vs. 24.1%, P= 0.036) and fatigue (3.2% vs. 3.4%, P= 0.737). Conclusions: Our results provide the first evidence that the adjuvant combination of nab-paclitaxel plus gemcitabine significantly improved DFS and OS of resected PDAC. Future RCTs with multi-center participation, particularly focused on adjuvant AG, can further provide information to confirm and strengthen these data.

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