Assessing Treatment Effect in Pancreatic Cancer

2012 ◽  
Vol 136 (1) ◽  
pp. 100-109 ◽  
Author(s):  
Douglas J Hartman ◽  
Alyssa M Krasinskas

Context.—Pancreatic cancer is one of the most deadly forms of cancer (43 140 new cases per year; 36 800 deaths), and most people with pancreatic cancer do not survive past 5 years. New therapeutic regimens are constantly being evaluated in an attempt to reduce the rapid progression of this disease. Although some patients receive neoadjuvant therapy in an attempt to make a nonresectable or borderline-resectable tumor resectable, more patients with resectable disease are being enrolled in clinical trials that provide neoadjuvant therapy. This means more pancreatic resections must be evaluated for therapy effect. Histologic grading schemes for the assessment of posttherapy response have been described, but difficulties associated with determining the histologic features of treatment effect in pancreatic cancer have not been addressed. Objectives.—To critically review the diagnostic criteria for proposed grading schemes for pancreatic cancer treated with neoadjuvant chemoradiation therapy and to provide guidance to surgical pathologists who encounter treated pancreatic cancer resections. Data Sources.—Published peer-reviewed literature and the personal experience of the authors. Conclusions.—Assessment of treatment effect in pancreatic cancer is difficult. Pathologists need to be aware that some histologic features of treatment effect overlap with histologic features seen in untreated pancreatic cancer, such as tumor cell anaplasia, necrosis, and fibrosis. Careful assessment of pancreatic resections, including detailed gross examination and thorough histologic sampling, is important in accurately assessing treatment effect and improving patient outcomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16781-e16781
Author(s):  
Jori Lee Kaplan ◽  
Benjamin Powers ◽  
Wenyi Fan ◽  
Michael J. Schell ◽  
Barbara Centeno ◽  
...  

e16781 Background: Borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) is a subset of pancreatic cancer with unique prognostic implications. A multimodality, neoadjuvant therapy (NAT) approach has known benefits such as downstaging tumors, reducing the risk of a positive margin, and treating micrometastatic disease. Patient selection and therapy sequencing are controversial owing to the high risk of recurrence. Therefore, we aimed to identify factors predicting recurrence and overall survival (OS) in BR PDAC patients undergoing NAT. Methods: We identified BR PDAC patients treated with NAT followed by surgery at Moffitt Cancer Center between 2008-2015. We evaluated clinical, demographic, and perioperative factors to identify predictors of recurrence and OS. Statistical analyses were performed with univariate and multivariable Cox regression models. Results: 117 patients with BR PDAC who received NAT were evaluated; 53 (45%) were female and 64 (55%) were male. Of those, 91 (78%) received gemcitabine/xeloda/taxotere and the remainder received other gemcitabine or 5FU regimens. 107 (91%) patients received neoadjuvant radiation, mainly 5-day dose painted SBRT. Post- NAT CA 19-9 normalized in 39 (33%) and 11 (9%) additional patients normalized after surgery. Pathologic treatment effect was appreciated in 85 (73%) patients and pathologic complete response (pCR) was seen in 18 (15%). 95 (81%) patients initiated adjuvant therapy. In multivariable analysis, the strongest predictor of recurrence was higher log(10) post-operative CA 19-9 (HR 2.29; 95% CI, 1.40-3.75). Time from initiation of NAT to surgery ≥ 5 months also predicted recurrence (HR 2.08; 95% CI, 1.16-3.72). In OS analysis, 71 patients had recurrence after multimodality treatment; 61 (86%) died and 10 (14%) were alive. In multivariable analysis, the strongest predictors of prolonged OS from recurrence were female gender (HR 0.47; 95% CI, 0.26-0.84) and presence of a treatment effect (HR 0.37; 95% CI, 0.15-0.93). Conclusions: We observed treatment effects and pCR comparable to other institutions, supporting a multimodality approach to BR PDAC. Higher post-operative CA 19-9 and time to surgery ≥ 5 months from initiation of NAT were associated with an increased risk of recurrence. These data suggest that timely receipt of surgery after completion of NAT may impact recurrence and OS in BR PDAC.


2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 


2019 ◽  
Author(s):  
Francis Igor Macedo ◽  
Danny Yakoub ◽  
Vikas Dudeja ◽  
Nipun B. Merchant

The incidence of pancreatic cancer continues to rise, and it is now the third-leading cause of cancer-related deaths in the United States. Only 15 to 20% of patients are eligible to undergo potentially curative resection, as most tumors are deemed unresectable at the time of diagnosis because of either locally advanced disease or distant metastases. Improvements in preoperative CT imaging have enabled better determination of the extent of disease and allowed for better operative planning. Based on their relationship to the surrounding vasculature and structures and presence or absence of distant disease, pancreatic tumors are classified into four categories: resectable, borderline resectable pancreatic cancer (BRPC), locally advanced pancreatic cancer (LAPC), and metastatic. With the recent advent of more effective chemotherapy regimens, efforts have focused on using neoadjuvant therapy approaches to increase the likelihood of achieving an R0 in patients with BRPC and possibly convert unresectable, locally advanced tumors to potentially resectable tumors. Response with neoadjuvant therapy regimens has resulted in increased number of patients eligible for resection, many times requiring vascular resection. Herein, we describe recent changes in the classification, important surgical and pathologic considerations and updated multimodal therapeutic options in the complex management of BRPC and LAPC.  This review contains 5 figures, 2 tables, and 78 references. Key Words: borderline resectable pancreatic cancer, CA 19-9, FOLFIRINOX, locally advanced pancreatic cancer, nab-paclitaxel, neoadjuvant chemotherapy, pancreatectomy, portal vein resection, radiation therapy, gemcitabine


2019 ◽  
Vol 18 (4) ◽  
pp. 373-378 ◽  
Author(s):  
June S Peng ◽  
Jane Wey ◽  
Sricharan Chalikonda ◽  
Daniela S Allende ◽  
R Matthew Walsh ◽  
...  

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