Abstract 404: A novel 4-gene score predict patient survival as well as pathologically complete (R0) resection in pancreatic cancer

Author(s):  
Masanori Oshi ◽  
Lan Le ◽  
Yoshihisa Tokumaru ◽  
Ankit Patel ◽  
Ryusei Matsuyama ◽  
...  
2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14679-e14679 ◽  
Author(s):  
Yuri Genyk ◽  
Lea Matsuoka ◽  
Anthony B. El-Khoueiry ◽  
Syma Iqbal ◽  
James Buxbaum ◽  
...  

e14679 Background: Locally advanced disease is found in about 40% of patients with pancreatic cancer at initial presentation. Tumors involving major visceral arteries are commonly deemed unresectable. In this study we analyzed the feasibility of R0 resection of locally advanced pancreatic cancer encasing major visceral arteries using arterial reconstruction. Methods: The following data were collected: age, gender, operative details, post-operative complications, chemotherapy and/or radiation therapy and overall and disease free survival. Patient survival was calculated utilizing Kaplan-Meier survival probability estimates. Results: From Dec., 2002 to Jan., 2012, 13 patients underwent pancreatic resection with concomitant resection and reconstruction of major visceral arteries for pancreatic cancer (9 males and 4 females, median age 63 yrs (range: 50–82 yrs)). The arterial involvement included celiac artery (n=6), superior mesenteric artery (n=4) and hepatic artery (n=3). Resections included pancreatico-duodenectomy (n=9), distal pancreatectomy (n=3), and total pancreatectomy (n=1). Management of the arterial involvement included: resection of celiac axis without reconstruction (n=2), reconstruction of one artery (n=6), two arteries (n=4) and three arteries (n=1). Nine of the 13 patients underwent simultaneous venous reconstruction. R0 resection was accomplished in 11, R1 in 1, and R2 in 1 patient. Ten of the 13 patients received neoadjuvant and/or adjuvant chemo- or chemo-radiation therapy outside protocols. To date, 4 patients are alive and disease free at 1, 4, 15 and 111 months, and 1 patient is alive with recurrence at 100 months. Six-month patient survival was 65% and median overall survival was 17 months. The probability of 5-year survival was 22%. Conclusions: Our study indicates that in select patients with locally advanced pancreatic cancer with involvement of major visceral arteries R0 resection is feasible by performing pancreatic resection with arterial reconstruction. The survival data in this group of patients are encouraging and provide the opportunity to reconsider the contraindications to surgical management of such patients.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 243-243
Author(s):  
Yuri Genyk ◽  
Afsaneh Barzi ◽  
Anthony B. El-Khoueiry ◽  
Lea Matsuoka ◽  
Vanessa Sutton ◽  
...  

243 Background: LAPC is found in about 40% of patients with pancreatic cancer at initial presentation. Tumors involving major visceral arteries are commonly deemed unresectable. In this study we analyzed the feasibility of R0 resection of LAPC encasing major visceral arteries using arterial resection and reconstruction. Methods: The following data were collected prospectively following pancreatic resection with vascular reconstruction in patients with LAPC: age, gender, operative details, post-operative complications, chemotherapy and/or radiation therapy and overall and disease free survival. Patient survival was calculated utilizing Kaplan-Meier survival probability estimates. Results: From Dec., 2002 to Sep., 2012, 12 patients with LAPC (8 males and 4 females, median age 58.5 yrs (range: 51–78 yrs)) underwent pancreatic resection with concomitant resection and reconstruction of major visceral arteries in our institution. The arterial involvement included celiac artery (n=8), and superior mesenteric artery (n=4). Resections included pancreatico-duodenectomy (n=8), distal pancreatectomy (n=3), and total pancreatectomy (n=1). Management of the arterial involvement included: resection of celiac axis without reconstruction (n=2), resection and reconstruction of one artery (n=6), two arteries (n=3) and three arteries (n=1). R0 resection was accomplished in 9, R1 in 2, and R2 in 1 patient. One patient (8%) died peri-operatively from pulmonary thromboembolism. Chemo- or chemo-radiation therapy was not protocolized. To date, 5 patients are alive and disease free at 7, 9, 11, 23 and 117 months, and 1 patient is alive with recurrence at 107 months. Six-month patient survival was 75% and median overall survival (MOS) was 19 months. Conclusions: The MOS in this patient population with systemic therapy is around 9 months. Although the sample size in our study is limited, observed MOS of 19 months is encouraging and provides the opportunity to reconsider the contraindications to surgical management of such patients with T4 LAPC. Timing of perioperative chemotherapy will be evaluated in a prospective trial.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3635
Author(s):  
Masanori Oshi ◽  
Yoshihisa Tokumaru ◽  
Ankit Patel ◽  
Li Yan ◽  
Ryusei Matsuyama ◽  
...  

Pathologically complete (R0) resection is essential for prolonged survival in pancreatic cancer. Survival depends not only on surgical technique, but also on cancer biology. A biomarker to predict survival is a critical need in pancreatic treatment. We hypothesized that this 4-gene score, which was reported to reflect cell proliferation, is a translatable predictive biomarker for pancreatic cancer. A total of 954 pancreatic cancer patients from multiple cohorts were analyzed and validated. Pancreatic cancer had the 10th highest median score of 32 cancers in The Cancer Genome Atlas (TCGA) cohort. The four-gene score significantly correlated with pathological grade and MKI67 expression. The high four-gene score enriched cell proliferation-related and cancer aggressiveness-related gene sets. The high score was associated with activation of KRAS, p53, transforming growth factor (TGF)-β, and E2F pathways, and with high alteration rate of KRAS and CDKN2A genes. The high score was also significantly associated with reduced CD8+ T cell infiltration of tumors, but with high levels of interferon-γ and cytolytic activity in tumors. The four-gene score correlated with the area under the curve of irinotecan and sorafenib in primary pancreatic cancer, and with paclitaxel and doxorubicin in metastatic pancreatic cancer. The high four-gene score was associated with significantly fewer R0 resections and worse survival. The novelty of the study is in the application of the four-gene score to pancreatic cancer, rather than the bioinformatics technique itself. Future analyses of inoperable lesions are expected to clarify the utility of our score as a predictive biomarker of systemic treatments.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2689
Author(s):  
Felix Popp ◽  
Ingracia Capino ◽  
Joana Bartels ◽  
Alexander Damanakis ◽  
Jiahui Li ◽  
...  

Pancreatic cancer features elaborate mechanisms of immune evasion. The potential of new immune molecules was explored to restore the antitumor immune response. If these immune molecules are associated with poor survival, specific drugs could take effect. Here, we analyze the expression of VISTA, LAG3, IDO, and TIM3 on tumor-infiltrating lymphocytes (TILs) and its impact on patient survival. We analyzed 153 pancreatic cancer patients from the prospectively managed database of the multicentered PANCALYZE study. Immunohistochemistry on a tissue microarray assessed VISTA, LAG3, IDO, and TIM3 expression of TILs from the patients undergoing primary resection. Complementarily, we analyzed publicly available transcriptomic data (n = 903). Successful completion of chemotherapy, and lymph node status were independent predictors of survival in the multivariate analysis of the clinicopathologic parameters. Fifteen tumors were exclusively VISTA-positive, thirteen tumors expressed VISTA together with TIM3, and ten tumors expressed VISTA together with IDO. Patients featuring tumors with high numbers of IDO-positive TILs had better patient survival (p = 0.037). VISTA, LAG3, and TIM3 expression did not correlate with survival. The analysis of publicly available data did not show survival differences. Tumors rarely co-express more than two immune molecules at the same time, and VISTA is most frequently co-expressed. Although IDO generally inhibits T-cell proliferation, a high expression of IDO was associated with improved survival. We expect immune checkpoint inhibitors against VISTA, LAG3, and TIM3 to be inefficient in a clinical application.


2017 ◽  
Vol 10 (2) ◽  
pp. 166-182 ◽  
Author(s):  
Shabia Shabir Khan ◽  
S.M.K. Quadri

Purpose As far as the treatment of most complex issues in the design is concerned, approaches based on classical artificial intelligence are inferior compared to the ones based on computational intelligence, particularly this involves dealing with vagueness, multi-objectivity and good amount of possible solutions. In practical applications, computational techniques have given best results and the research in this field is continuously growing. The purpose of this paper is to search for a general and effective intelligent tool for prediction of patient survival after surgery. The present study involves the construction of such intelligent computational models using different configurations, including data partitioning techniques that have been experimentally evaluated by applying them over realistic medical data set for the prediction of survival in pancreatic cancer patients. Design/methodology/approach On the basis of the experiments and research performed over the data belonging to various fields using different intelligent tools, the authors infer that combining or integrating the qualification aspects of fuzzy inference system and quantification aspects of artificial neural network can prove an efficient and better model for prediction. The authors have constructed three soft computing-based adaptive neuro-fuzzy inference system (ANFIS) models with different configurations and data partitioning techniques with an aim to search capable predictive tools that could deal with nonlinear and complex data. After evaluating the models over three shuffles of data (training set, test set and full set), the performances were compared in order to find the best design for prediction of patient survival after surgery. The construction and implementation of models have been performed using MATLAB simulator. Findings On applying the hybrid intelligent neuro-fuzzy models with different configurations, the authors were able to find its advantage in predicting the survival of patients with pancreatic cancer. Experimental results and comparison between the constructed models conclude that ANFIS with Fuzzy C-means (FCM) partitioning model provides better accuracy in predicting the class with lowest mean square error (MSE) value. Apart from MSE value, other evaluation measure values for FCM partitioning prove to be better than the rest of the models. Therefore, the results demonstrate that the model can be applied to other biomedicine and engineering fields dealing with different complex issues related to imprecision and uncertainty. Originality/value The originality of paper includes framework showing two-way flow for fuzzy system construction which is further used by the authors in designing the three simulation models with different configurations, including the partitioning methods for prediction of patient survival after surgery. Several experiments were carried out using different shuffles of data to validate the parameters of the model. The performances of the models were compared using various evaluation measures such as MSE.


2007 ◽  
Vol 11 (5) ◽  
pp. 1162-1174 ◽  
Author(s):  
N. Valkovskaya ◽  
H. Kayed ◽  
K. Felix ◽  
D. Hartmann ◽  
N. A. Giese ◽  
...  

Pancreas ◽  
2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Yixing Wu ◽  
Huatian Huang ◽  
Beatrice Fervers ◽  
Lingeng Lu

Oncotarget ◽  
2017 ◽  
Vol 8 (62) ◽  
pp. 104796-104805
Author(s):  
Ana-Barbara García-García ◽  
M. Carmen Gómez-Mateo ◽  
Rebeca Hilario ◽  
Pilar Rentero-Garrido ◽  
Alvaro Martínez-Domenech ◽  
...  

Author(s):  
Quisette P. Janssen ◽  
Jacob L. van Dam ◽  
Isabelle G. Kivits ◽  
Marc G. Besselink ◽  
Casper H. J. van Eijck ◽  
...  

Abstract Background The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy. Methods A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes. Results We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4–34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0–37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable. Conclusions In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.


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