The Experts below are selected from a list of 36453 Experts worldwide ranked by ideXlab platform
Tom Brody - One of the best experts on this subject based on the ideXlab platform.
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Chapter 17 – Neoadjuvant Therapy Versus Adjuvant Therapy
Clinical Trials, 2016Co-Authors: Tom BrodyAbstract:This chapter describes an aspect of study design for oncology clinical trials (and in daily oncology clinical practice), namely, the choice of Neoadjuvant Therapy, which occurs before surgery, and adjuvant Therapy, which occurs after Therapy. Neoadjuvant Therapy and adjuvant Therapy each have specific advantages. Often, clinical trials in oncology include study arms that test both of these approaches to study design.
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Neoadjuvant Therapy versus Adjuvant Therapy
Clinical Trials, 2012Co-Authors: Tom BrodyAbstract:This chapter describes an aspect of study design for oncology clinical trials (and in daily oncology clinical practice), namely, the choice of Neoadjuvant Therapy, which occurs before surgery, and adjuvant Therapy, which occurs after Therapy. Neoadjuvant Therapy and adjuvant Therapy each have specific advantages. Often, clinical trials in oncology include study arms that test both of these approaches to study design.
Reetesh K Pai - One of the best experts on this subject based on the ideXlab platform.
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Pathologic assessment of gastrointestinal tract and pancreatic carcinoma after Neoadjuvant Therapy
Modern Pathology, 2018Co-Authors: Reetesh K PaiAbstract:Neoadjuvant Therapy is increasingly used to treat patients with a wide variety of malignancies. Histologic evaluation of treated specimens provides important prognostic information and may guide subsequent chemoTherapy. Neoadjuvant Therapy is commonly employed in the treatment of locally advanced rectal adenocarcinoma, hepatic colorectal metastases, esophageal/esophagogastric junction carcinoma, and pancreatic ductal adenocarcinoma. Numerous tumor regression schemes have been used in these tumors and standardized approaches to evaluate these specimens are needed. In this review, the various tumor regression scoring systems that have been used in these organs are described and their associations with clinical outcomes are discussed. Recommendations regarding how to handle and report the histologic findings in these resections specimens are provided.
Martin S Taylor - One of the best experts on this subject based on the ideXlab platform.
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tumor microenvironment immune response in pancreatic ductal adenocarcinoma patients treated with Neoadjuvant Therapy
Journal of the National Cancer Institute, 2020Co-Authors: Theodoros Michelakos, Lei Cai, Vincenzo Villani, Francesco Sabbatino, Filippos Kontos, Carlos Fernandezdel Castillo, Teppei Yamada, Azfar Neyaz, Martin S TaylorAbstract:BACKGROUND Neoadjuvant FOLFIRINOX and chemoradiation have been utilized to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether Neoadjuvant Therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether Neoadjuvant Therapy induces an immune response towards PDAC. METHODS Clinicopathologic variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016). Neoadjuvant regimens included FOLFIRINOX with/without chemoradiation, proton chemoradiation (25Gy), photon chemoradiation (50.4Gy) or no Neoadjuvant Therapy. HLA class I and II expression, and immune cell infiltration (CD4+, FoxP3+, CD8+, Granzyme B+ cells and M2 macrophages) were analyzed immunohistochemically and correlated with clinicopathologic variables. The antitumor immune response was compared among Neoadjuvant Therapy regimens. All statistical tests were two-sided. RESULTS Two hundred forty-eight PDAC patients were included. Median age was 64y; 50.0% were female. HLA-A defects were less frequent in the FOLFIRINOX cohort (p=.006). HLA class II expression was lowest in photon and highest in proton patients (p=.02). The FOLFIRINOX cohort exhibited the densest CD8+ cell infiltration (p<.001). FOLFIRINOX and proton patients had the highest CD4+ and lowest T regulatory (FoxP3+) cell density, respectively. M2 macrophage density was statistically significantly higher in the treatment-naive group (p<.001), in which dense M2 macrophage infiltration was an independent predictor of poor OS. CONCLUSIONS Neoadjuvant FOLFIRINOX with/without chemoradiation may induce immunologically relevant changes in the tumor microenvironment. It may reduce HLA-A defects, increase CD8+ cell density and decrease T regulatory cell and M2 macrophage density. Therefore, Neoadjuvant FOLFIRINOX Therapy may benefit from combinations with checkpoint inhibitors, which can enhance patients' antitumor immune response.
Lei Cai - One of the best experts on this subject based on the ideXlab platform.
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tumor microenvironment immune response in pancreatic ductal adenocarcinoma patients treated with Neoadjuvant Therapy
Journal of the National Cancer Institute, 2020Co-Authors: Theodoros Michelakos, Lei Cai, Vincenzo Villani, Francesco Sabbatino, Filippos Kontos, Carlos Fernandezdel Castillo, Teppei Yamada, Azfar Neyaz, Martin S TaylorAbstract:BACKGROUND Neoadjuvant FOLFIRINOX and chemoradiation have been utilized to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether Neoadjuvant Therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether Neoadjuvant Therapy induces an immune response towards PDAC. METHODS Clinicopathologic variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016). Neoadjuvant regimens included FOLFIRINOX with/without chemoradiation, proton chemoradiation (25Gy), photon chemoradiation (50.4Gy) or no Neoadjuvant Therapy. HLA class I and II expression, and immune cell infiltration (CD4+, FoxP3+, CD8+, Granzyme B+ cells and M2 macrophages) were analyzed immunohistochemically and correlated with clinicopathologic variables. The antitumor immune response was compared among Neoadjuvant Therapy regimens. All statistical tests were two-sided. RESULTS Two hundred forty-eight PDAC patients were included. Median age was 64y; 50.0% were female. HLA-A defects were less frequent in the FOLFIRINOX cohort (p=.006). HLA class II expression was lowest in photon and highest in proton patients (p=.02). The FOLFIRINOX cohort exhibited the densest CD8+ cell infiltration (p<.001). FOLFIRINOX and proton patients had the highest CD4+ and lowest T regulatory (FoxP3+) cell density, respectively. M2 macrophage density was statistically significantly higher in the treatment-naive group (p<.001), in which dense M2 macrophage infiltration was an independent predictor of poor OS. CONCLUSIONS Neoadjuvant FOLFIRINOX with/without chemoradiation may induce immunologically relevant changes in the tumor microenvironment. It may reduce HLA-A defects, increase CD8+ cell density and decrease T regulatory cell and M2 macrophage density. Therefore, Neoadjuvant FOLFIRINOX Therapy may benefit from combinations with checkpoint inhibitors, which can enhance patients' antitumor immune response.
Jennifer F. Tseng - One of the best experts on this subject based on the ideXlab platform.
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Neoadjuvant Therapy affects margins and margins affect all: perioperative and survival outcomes in resected pancreatic adenocarcinoma
HPB : the official journal of the International Hepato Pancreato Biliary Association, 2018Co-Authors: Susanna W.l. De Geus, Gyulnara G. Kasumova, Teviah Sachs, Tara S. Kent, A. James Moser, Alexander L. Vahrmeijer, Mark P. Callery, Jennifer F. TsengAbstract:Abstract Background Resection margin status is an important prognostic factor in pancreatic cancer; however, the impact of positive resection margins in those who received Neoadjuvant Therapy remains unclear. The current study investigates the prognostic impact of resection margin status after Neoadjuvant Therapy and pancreaticoduodenectomy for patients with pancreatic adenocarcinoma. Methods Patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma between 2006 and 2013 were identified from the National Cancer Database. Multivariable logistic regression analysis was utilized to examine the predictive value of Neoadjuvant Therapy for resection margin status. Long-term outcomes were compared using a Cox proportional hazards model. Results 7917 patients were identified in total: 1077 (13.6%) and 6840 (86.4%) patients received Neoadjuvant Therapy and upfront surgery, respectively. Upfront surgery was independently predictive of a positive margin (25.7% vs. 17.7%; OR, 1.54) compared to Neoadjuvant Therapy. After receipt of Neoadjuvant Therapy, positive margins (median overall survival, 18.5 vs. 25.9 months; HR, 1.58) remained significantly associated with poor survival on multivariable analysis. Discussion While Neoadjuvant Therapy is associated with decreased R1/R2-resection rates after pancreaticoduodenectomy, the poor prognostic impact of positive margins is not abrogated by Neoadjuvant Therapy, stressing the need for complete tumor clearance and postoperative treatment even after Neoadjuvant Therapy.
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Neoadjuvant Therapy versus upfront surgical strategies in resectable pancreatic cancer a markov decision analysis
Ejso, 2016Co-Authors: S W L De Geus, Douglas B. Evans, Lindsay A Bliss, Mariam F Eskander, J K Smith, Robert A Wolff, Rebecca A Miksad, Milton C Weinstein, Jennifer F. TsengAbstract:Abstract Background Neoadjuvant Therapy is gaining acceptance as a valid treatment option for borderline resectable pancreatic cancer; however, its value for clearly resectable pancreatic cancer remains controversial. The aim of this study was to use a Markov decision analysis model, in the absence of adequately powered randomized trials, to compare the life expectancy (LE) and quality-adjusted life expectancy (QALE) of Neoadjuvant Therapy to conventional upfront surgical strategies in resectable pancreatic cancer patients. Methods A Markov decision model was created to compare two strategies: attempted pancreatic resection followed by adjuvant chemoradioTherapy and Neoadjuvant chemoradioTherapy followed by restaging with, if appropriate, attempted pancreatic resection. Data obtained through a comprehensive systematic search in PUBMED of the literature from 2000 to 2015 were used to estimate the probabilities used in the model. Deterministic and probabilistic sensitivity analyses were performed. Results Of the 786 potentially eligible studies identified, 22 studies met the inclusion criteria and were used to extract the probabilities used in the model. Base case analyses of the model showed a higher LE (32.2 vs. 26.7 months) and QALE (25.5 vs. 20.8 quality-adjusted life months) for patients in the Neoadjuvant Therapy arm compared to upfront surgery. Probabilistic sensitivity analyses for LE and QALE revealed that Neoadjuvant Therapy is favorable in 59% and 60% of the cases respectively. Conclusion(s) Although conceptual, these data suggest that Neoadjuvant Therapy offers substantial benefit in LE and QALE for resectable pancreatic cancer patients. These findings highlight the value of further prospective randomized trials comparing Neoadjuvant Therapy to conventional upfront surgical strategies.
