Recurrence in Patients Achieving Pathological Complete Response After Neoadjuvant Treatment for Advanced Pancreatic Cancer.

Published on Jul 1, 2021in Annals of Surgery10.13
· DOI :10.1097/SLA.0000000000003570
Alex B. Blair17
Estimated H-index: 17
(Johns Hopkins University),
Ling Di Yin (JHUSOM: Johns Hopkins University School of Medicine)+ 10 AuthorsJin He40
Estimated H-index: 40
(Johns Hopkins University)
Sources
Abstract
OBJECTIVE: The aim of this study was to characterize the patterns and treatment of disease recurrence in patients achieving a pathological complete response (pCR) following neoadjuvant chemoradiation for advanced pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: A pCR is an independent predictor for improved survival in PDAC. However, disease recurrence is still observed in these patients. METHODS: Patients with advanced PDAC who were treated with neoadjuvant therapy and had a pCR were identified between 2009 and 2017. Overall survival (OS) was determined from the initiation of neoadjuvant, disease-free survival (DFS) from the date of surgery, and post-recurrence survival (PRS) from the date of recurrence. Factors associated with recurrence were analyzed using a Cox-regression model. RESULTS: Of 331 patients with borderline resectable or locally advanced PDAC, 30 achieved a pCR following neoadjuvant treatment and pancreatectomy. The median DFS for pCR patients was 29 months and OS 76 months. Recurrence was observed in 14 patients. No clinicopathologic or treatment characteristics were associated with survival. The median PRS following recurrence was 25 months. Treatment following recurrence included chemotherapy, radiation or ablation, and surgical resection. Hepatectomy or completion pancreatectomy was accomplished in 2 patients that remain alive 13 and 62 months, respectively, following metastasectomy. CONCLUSIONS: A pCR following neoadjuvant therapy in patients with advanced PDAC is associated with remarkable survival, although recurrence occurs in about half of patients. Nevertheless, patients with pCR and recurrence respond well to treatment and survival remains encouraging. Advanced molecular characterization and longitudinal liquid biopsy may offer additional assistance with understanding tumor biologic behavior after achieving a pCR.
📖 Papers frequently viewed together
20203.36Surgery
10 Authors (Shiwei Guo, ..., Gang Jin)
6 Citations
20193.96Ejso
17 Authors (Mariko Asaoka, ..., Takashi Ishikawa)
6 Citations
References36
Newest
#1Mark J. TrutyH-Index: 31
#2Michael L. KendrickH-Index: 58
Last. Axel GrotheyH-Index: 86
view all 14 authors...
MiniTotal neoadjuvant therapy, or systemic induction chemotherapy followed by chemoradiation, is an optimal preoperative sequencing strategy for patients with borderline resectable or locally advanced pancreatic adenocarcinoma. This strategy allows high rate of negative margins despite low frequency
105 CitationsSource
#1Vincent P. Groot (UU: Utrecht University)H-Index: 16
#2Alex B. Blair (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 17
Last. Jin He (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 40
view all 12 authors...
Abstract Introduction The incidence, timing, and implications of recurrence in patients who underwent neoadjuvant treatment and surgical resection of borderline resectable (BRPC) or locally advanced (LAPC) pancreatic cancer are not well established. Materials and methods Patients with BRPC/LAPC who underwent post-neoadjuvant resection between 2007 and 2015 were included. Associations between clinicopathologic characteristics and specific recurrence locations, recurrence-free survival (RFS), and ...
23 CitationsSource
#1Georgios Gemenetzis (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 17
#2Vincent P. Groot (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 16
Last. Jin He (Johns Hopkins University)H-Index: 40
view all 14 authors...
Objective:The aim of the study was to identify the survival of patients with locally advanced pancreatic cancer (LAPC) and assess the effect of surgical resection after neoadjuvant therapy on patient outcomes.Background:An increasing number of LAPC patients who respond favorably to neoadjuvant thera
115 CitationsSource
#1Vincent P. Groot (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 16
#2Georgios Gemenetzis (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 17
Last. Jin HeH-Index: 40
view all 13 authors...
Objectives:To establish an evidence-based cut-off to differentiate between early and late recurrence and to compare clinicopathologic risk factors between the two groups.Summary Background Data:A clear definition of “early recurrence” after pancreatic ductal adenocarcinoma resection is currently lac
95 CitationsSource
#1Ammar A. Javed (Johns Hopkins University)H-Index: 23
#2Michael J. Wright (Johns Hopkins University)H-Index: 5
Last. Jin He (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 40
view all 15 authors...
Introduction Approximately, 20% of patients with pancreatic ductal adenocarcinoma have resectable disease at diagnosis. Given improvements in locoregional and systemic therapies, some patients with borderline resectable pancreatic cancer (BRPC) can now undergo successful resection. The outcomes of patients with BRPC after neoadjuvant therapy remain unclear.
29 CitationsSource
#1Georgios Gemenetzis (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 17
#2Vincent P. Groot (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 16
Last. Christopher L. WolfgangH-Index: 102
view all 13 authors...
OBJECTIVES: Previous retrospective studies demonstrated that circulating tumor cells (CTCs) subtypes correlate with overall survival in patients with pancreatic ductal adenocarcinoma (PDAC). Herein, we report results of a prospective observational study on CTCs dynamics to assess their clinical significance. METHODS: The CLUSTER study is a prospective longitudinal study on PDAC CTCs dynamics (NCT02974764). Multiple peripheral blood samples were collected from 200 consecutively enrolled patients ...
57 CitationsSource
#1Jin He (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 40
#2Alex B. Blair (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 17
Last. Christopher L. Wolfgang (Johns Hopkins University)H-Index: 102
view all 16 authors...
Objectives:To describe the survival outcome of patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) who have a pathologic complete response (pCR) following neoadjuvant chemoradiation.Background:Patients with BR/LA-PDAC are often treated with neoadjuva
79 CitationsSource
#1Vincent P. Groot (UU: Utrecht University)H-Index: 16
#2Georgios Gemenetzis (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 17
Last. Jin He (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 40
view all 15 authors...
Background After radical resection of pancreatic ductal adenocarcinoma (PDAC), approximately 80% of patients will develop disease recurrence. It remains unclear to what extent the location of recurrence carries prognostic significance. Additionally, stratifying the pattern of recurrence may lead to a deeper understanding of the heterogeneous biological behavior of PDAC.
40 CitationsSource
#1Alex B. Blair (Johns Hopkins University)H-Index: 17
#2Lauren M. Rosati (Johns Hopkins University)H-Index: 14
Last. Jin He (Johns Hopkins University)H-Index: 40
view all 11 authors...
Abstract Background The impact of neoadjuvant stereotactic body radiation therapy on postoperative complications for patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma remains unclear. Limited studies have compared neoadjuvant stereotactic body radiation therapy versus conventional chemoradiation therapy. A retrospective study was performed to determine if perioperative complications were different among patients with borderline resectable or locally advance...
20 CitationsSource
#1Jordan M. Cloyd (University of Texas MD Anderson Cancer Center)H-Index: 24
#2Huamin Wang (University of Texas MD Anderson Cancer Center)H-Index: 82
Last. Matthew H.G. KatzH-Index: 66
view all 21 authors...
Importance We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined. Objective To identify clinical factors associated with major pathologic response in a large cohor...
58 CitationsSource
Cited By6
Newest
#1Alex B. Blair (Johns Hopkins University)H-Index: 17
#2Robert W. KrellH-Index: 17
Last. Jin He (Johns Hopkins University)H-Index: 40
view all 12 authors...
BACKGROUND AND PURPOSE There is limited high-level evidence to guide locally advanced pancreas cancer (LAPC) management. Recent work shows that surgeons' preferences in LAPC management vary broadly. We sought to examine whether surgeon volume was associated with attitudes regarding LAPC management. METHODS An electronic survey was distributed by email to an international cohort of pancreas surgeons to evaluate practice patterns regarding LAPC management. Clinical vignette-based questions evaluat...
Source
Background Pancreatic cancer remains a relevant clinical problem due to poor prognosis. Even after curative pancreaticoduodenectomy tumor recurrences occur in up to 80%. Risk factors for postoperative tumor recurrences have been identified before, but data on risk factors for tumor recurrences in patients with long-term-survival is scarce. Methods In this retrospective study consecutive long-term survival-patients (defined as at least 60 months survival) undergoing pancreaticoduodenectomy for pa...
Source
#1Yanming Zhou (Ha Tai: Xiamen University)H-Index: 22
#2Shan Liao (Ha Tai: Xiamen University)
Last. Jun You (Ha Tai: Xiamen University)
view all 3 authors...
BACKGROUND There is a scarcity of data about patients with pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant therapy before radical resection and achieved a pathological complete response (pCR). The aim of this study was to describe the recurrence and survival in this subset of patients. METHODS The Embase, Web of Science and PubMed databases were systematically searched for eligible studies published between January 2000 and August 2020. Clinicopathological data of individual pat...
Source
#1Vincent P. Groot (UU: Utrecht University)H-Index: 16
#2Lois A. Daamen (UU: Utrecht University)H-Index: 6
Last. I. Quintus Molenaar (UU: Utrecht University)H-Index: 31
view all 5 authors...
An accurate understanding of pancreatic cancer recurrence after seemingly successful surgery is essential for the development of novel strategies that can improve outcomes for patients. Currently, disease recurrence occurs in up to 80–90% of patients after resection and is the main cause of disease-specific mortality. The main recurrence patterns following resection for pancreatic cancer include hepatic metastases, peritoneal carcinomatosis, locoregional recurrence and pulmonary metastases. More...
Source
#1Lingdi Yin (Nanjing Medical University)H-Index: 5
#2Ning Pu (Johns Hopkins University)
Last. Jun Yu (Johns Hopkins University)H-Index: 154
view all 6 authors...
Purpose: To evaluate somatic mutations, circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in patients with Pancreatic ductal adenocarcinoma (PDAC) with pathologic complete response (pCR) to neoadjuvant therapy (NAT) and find their associations with outcome. Experimental Design: Thirty-six patients with PDAC with pCR were identified from 2009 to 2017. Macrodissection was performed on resected specimens to isolate DNA from 332 regions of interest including fibrosis, normal duct, nor...
5 CitationsSource
#1Patricia Santofimia-Castaño (AMU: Aix-Marseille University)H-Index: 8
#2Juan L. Iovanna (AMU: Aix-Marseille University)H-Index: 82
Abstract Pancreatic cancer is the fourth most common cause of cancer-associated death in western countries, where the incidence and number of deaths are increasing every year. Intrinsic or acquired resistance of tumor cells to chemotherapy agents is the major reason for failure of traditional cancer treatment. Several factors are implicated in this impressive resistance; however, of these, it is important to highlight the extensive cellular heterogeneity of these tumors. This heterogeneity is li...
4 CitationsSource