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Neoadjuvant Treatment Strategies in Resectable Pancreatic Cancer. Cancers (Basel) 2021; 13:cancers13184724. [PMID: 34572951 PMCID: PMC8469083 DOI: 10.3390/cancers13184724] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/15/2021] [Accepted: 09/15/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Only 10–20% of patients with newly diagnosed resectable pancreatic adenocarcinoma have potentially resectable disease. Upfront surgery is the gold standard, but it is rarely curative. After surgical extirpation of tumors, up to 80% of patients will develop cancer recurrence, and the initial relapse is metastatic in 50–70% of these patients. Adjuvant chemotherapy offers the best strategy to date to improve overall survival but faces real challenges; some patients will experience rapid disease progression within 3 months of surgery and patients who do not receive all planned cycles of chemotherapy have unfavourable oncological outcomes. The neoadjuvant approach is therefore logical but requires further investigation. This approach shows favourable trends regarding disease-free survival and overall survival but, in the absence of rigorous published phase III trials, is not validated to date. Here, we intend to provide a comprehensive analysis of the literature to provide direction for future studies. Abstract Complete surgical resection is the cornerstone of curative therapy for resectable pancreatic adenocarcinoma. Upfront surgery is the gold standard, but it is rarely curative. Neoadjuvant treatment is a logical option, as it may overcome some of the limitations of adjuvant therapy and has already shown some encouraging results. The main concern regarding neoadjuvant therapy is the risk of disease progression during chemotherapy, meaning the opportunity to undergo the intended curative surgery is missed. We reviewed all recent literature in the following areas: major surveys, retrospective studies, meta-analyses, and randomized trials. We then selected the ongoing trials that we believe are of interest in this field and report here the results of a comprehensive review of the literature. Meta-analyses and randomized trials suggest that neoadjuvant treatment has a positive effect. However, no study to date can be considered practice changing. We considered design, endpoints, inclusion criteria and results of available randomized trials. Neoadjuvant treatment appears to be at least a feasible strategy for patients with resectable pancreatic cancer.
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Gleeson EM, Leigh N, Golas BJ, Magge D, Sarpel U, Hiotis SP, Labow DM, Pintova S, Cohen NA. Adjuvant Chemotherapy Is Not Guided by Pathologic Treatment Effect After Neoadjuvant Chemotherapy in Pancreatic Cancer. Pancreas 2021; 50:1163-1168. [PMID: 34714279 DOI: 10.1097/mpa.0000000000001881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Currently, there is no guidance for optimal adjuvant chemotherapy selection after pancreatectomy with a partial or poor response to neoadjuvant therapy. This study seeks to describe an institution's practice patterns of adjuvant chemotherapy selection after neoadjuvant therapy. METHODS Patients at a single institution receiving neoadjuvant chemotherapy followed by pancreatectomy for pancreatic cancer were reviewed. Patients enrolled in trials or without follow-up were excluded. Types of chemotherapy, the College of American Pathologists pathologic tumor response, and medical oncology plans were recorded. RESULTS Forty-one patients met inclusion criteria. Pathologic review of treatment effect demonstrated that 3 patients (7.3%) had complete pathologic response, 3 (7.3%) had near complete pathologic response, 16 (39%) had partial response, and 14 (34.1%) had poor/no response to neoadjuvant chemotherapy. Fourteen of the 30 patients with partial or poor response (46.7%) received an alternate adjuvant regimen. Pathologic response to neoadjuvant chemotherapy specifically guided therapy in 11 (30.5%) patients. CONCLUSIONS Despite 73.1% of patients with partial or poor response to neoadjuvant chemotherapy, only 46.7% received a different adjuvant regimen. Medical oncologists infrequently considered treatment effect when choosing adjuvant therapy. Pathologic response to neoadjuvant chemotherapy should be considered when selecting adjuvant chemotherapy.
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Affiliation(s)
| | - Natasha Leigh
- From the Division of Surgical Oncology, Department of Surgery
| | | | - Deepa Magge
- From the Division of Surgical Oncology, Department of Surgery
| | - Umut Sarpel
- From the Division of Surgical Oncology, Department of Surgery
| | - Spiros P Hiotis
- From the Division of Surgical Oncology, Department of Surgery
| | - Daniel M Labow
- From the Division of Surgical Oncology, Department of Surgery
| | - Sofya Pintova
- Division of Hematology and Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Noah A Cohen
- From the Division of Surgical Oncology, Department of Surgery
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Watanabe G, Ushida Y, Oba A, Ono Y, Sato T, Inoue Y, Takahashi Y, Saiura A, Ito H. Impact of Tumor Size on the Outcomes of Patients with Resectable Distal Pancreatic Cancer: Lessons Learned from a Series of 158 Radical Resections. Ann Surg Oncol 2021; 29:378-388. [PMID: 34403004 DOI: 10.1245/s10434-021-10560-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 07/19/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Neoadjuvant therapy is used for borderline resectable pancreatic ductal adenocarcinoma (PDAC) with high risk of incomplete resection and early recurrence. Because distal PDAC is rare, the optimal criteria for neoadjuvant therapy specific for distal PDAC remain unclear. We hypothesized large distal PDAC would recur earlier than small distal PDAC. OBJECTIVE The aim of this study was to identify the risk factors for failure of upfront resection for resectable distal PDAC. METHODS The study cohort comprised 158 patients with resectable distal PDAC who underwent radical resection. The long-term outcomes were recurrence-free survival (RFS), disease-specific survival (DSS), and post-recurrence survival (PRS). RESULTS R0 resection was achieved in 92% of patients, and median DSS for the entire cohort was 31 months. Among 103 patients who developed recurrence, 32 (31%) developed recurrence within 6 months. The median PRS and DSS for those with early recurrence was 6 and 10 months, respectively, compared with 11 and 30 months, respectively, for those with late recurrence (p = 0.017 and p < 0.001, respectively). Patients with tumors > 4 cm had higher rates of R1 resection (16%) and concomitant resection of another organ (19%) than those with smaller tumors (4% and 2%, p = 0.009 and p < 0.001, respectively). In multivariate analysis, tumor > 4 cm remained a significant predictor of early recurrence (p < 0.001, hazard ratio [HR] 6.51), shorter RFS (p = 0.018, HR 1.71), and shorter DSS (p = 0.002, HR 2.07). CONCLUSION Tumor size > 4 cm is a reliable predictor of early recurrence after resection of distal PDAC, and neoadjuvant therapy may help select patients who can benefit from radical resection.
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Affiliation(s)
- Genki Watanabe
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuta Ushida
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Atsushi Oba
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshihiro Ono
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takafumi Sato
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yu Takahashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akio Saiura
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Hiromichi Ito
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
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Rieser CJ, Narayanan S, Bahary N, Bartlett DL, Lee KK, Paniccia A, Smith K, Zureikat AH. Optimal management of patients with operable pancreatic head cancer: A Markov decision analysis. J Surg Oncol 2021; 124:801-809. [PMID: 34231222 DOI: 10.1002/jso.26589] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/11/2021] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Neoadjuvant therapy (NAT) is an emerging strategy for operable pancreatic ductal adenocarcinoma (PDAC). While NAT increases multimodal therapy completion, it risks functional decline and treatment dropout. We used decision analysis to determine optimal management of localized PDAC and consider risks faced by elderly patients. METHODS A Markov cohort decision analysis model evaluated treatment options for a 60-year-old patient with resectable PDAC: (1) upfront pancreaticoduodenectomy or (2) NAT. One-way and probabilistic sensitivity analyses were performed. A subanalysis considered the scenario of a 75-year-old patient. RESULTS For the base case, NAT offered an incremental survival gain of 4.6 months compared with SF (overall survival: 26.3 vs. 21.7 months). In one-way sensitivity analyses, findings were sensitive to recurrence-free survival for NAT patients undergoing adjuvant, probability of completing NAT, and probability of being resectable at exploration after NAT. On probabilistic analysis, NAT was favored in a majority of trials (97%) with a median survival benefit of 5.1 months. In altering the base case for the 75-year-old scenario, NAT had a survival benefit of 3.8 months. CONCLUSIONS This analysis demonstrates a significant benefit to NAT in patients with localized PDAC. This benefit persists even in the elderly cohort.
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Affiliation(s)
- Caroline J Rieser
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Sowmya Narayanan
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Nathan Bahary
- Department of Medical Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - David L Bartlett
- AHN Cancer Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA
| | - Kenneth K Lee
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Alessandro Paniccia
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kenneth Smith
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis. J Clin Med 2020; 9:jcm9072132. [PMID: 32640720 PMCID: PMC7408905 DOI: 10.3390/jcm9072132] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 06/29/2020] [Accepted: 07/01/2020] [Indexed: 12/24/2022] Open
Abstract
Background: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. Methods: The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. Results: 26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52–0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs. 27% OR 0.39 (CI 0.22–0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44–0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34–0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts (p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05–0.32), p = 0.015). Conclusion: NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease.
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Aziz H, Zeeshan M, Jie T, Maegawa FB. Neoadjuvant Chemoradiation Therapy is Associated with Adverse Outcomes in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Cancer. Am Surg 2020. [DOI: 10.1177/000313481908501136] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The use of neoadjuvant chemoradiation therapy in patients with pancreatic adenocarcinoma is emerg-ing as an acceptable therapy option. The effects of neoadjuvant therapy on 30 days’ outcomes in patients with pancreatic cancer are not well defined in the literature. NSQIP (2009–2012) was used. Only patients with a diagnosis of pancreatic cancer and those who underwent a Whipple were included in the analysis. Patient who underwent neoadjuvant chemoradiation therapy were compared with those who did not receive therapy. Main outcome measures were as follows: complications, ≥2 units of blood transfusions, length of stay, readmission rates, return to the operating room, and 30-day mortality. A total of 1445 patients (395: neoadjuvant chemoradiation and 1050: no neoadjuvant therapy) were identified. The mean age was 67 ± 12 years, and 51 per cent of the patients were male. Neoadjuvant chemoradiation therapy was associated with increase in readmission rates (18% vs 12.2%, P 0.02), unanticipated return to the operating room (2.3% vs 1.1%, P 0.03) with no difference in mortality rates. Neoadjuvant chemoradiation therapy is associated with increase in inhospital complications. These differences in outcomes may be explained by the more advance stage of pancreatic cancer in these subsets of patients. Resource utilization and preoperative rehabilitation are of utmost significance to overcome this rise in complications associated with neoadjuvant chemoradiation therapy.
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Affiliation(s)
- Hassan Aziz
- Division of Hepatobiliary, Pancreas, and Abdominal Organ Transplantation at Keck Hospital of USC, Los Angeles, California
| | - Muhammad Zeeshan
- Department of Surgery, Westchester Medical Center, Valhalla, New York
| | - Tun Jie
- Department of Surgery, University of Arizona College of Medicine, Tucson, Arizona; and
| | - Felipe B. Maegawa
- Department of Surgery, Southern Arizona Veterans Affairs Health Care System, Tucson, Arizona
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Eguchi H, Takeda Y, Takahashi H, Nakahira S, Kashiwazaki M, Shimizu J, Sakai D, Isohashi F, Nagano H, Mori M, Doki Y. A Prospective, Open-Label, Multicenter Phase 2 Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 2019; 26:4498-4505. [PMID: 31440928 DOI: 10.1245/s10434-019-07735-8] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Neoadjuvant therapy reportedly shows only marginal clinical benefit in pancreatic ductal adenocarcinoma (PDAC), especially in resectable cases. However, with more effective regimens, neoadjuvant therapy may become a standard of care for resectable cases. A prospective, open-label, multicenter phases 1 and 2 trial of neoadjuvant therapy was conducted using full-dose gemcitabine and S-1 concurrently with 50.4 Gy of radiation therapy (GSRT) for resectable PDAC. This report describes the phase 2 results. METHODS The phase 2 part of this study enrolled 57 patients with cytologically or histologically proven PDAC deemed resectable based on imaging before neoadjuvant therapy. These patients received GSRT. After reevaluation by computed tomography scan, surgical exploration was performed, followed by adjuvant therapy. According to the prescribed protocol of the clinical trial, statistical analyses included 57 phase 2 patients and 6 phase 1 patients who received the same dosage as in phase 2. RESULTS This trial enrolled 63 patients (42 men and 21 women) with a median age of 70 years. Leukopenia or neutropenia of grade 3 or higher occurred for 79% of the patients, but no other severe adverse events were observed. Among the 63 patients, 54 underwent surgical resection. Intention-to-treat analysis of the 63 patients showed an excellent median survival time lasting as long as 55.3 months. The patients who completed neoadjuvant therapy, surgery, and adjuvant therapy had a 5-year survival rate of 56.6%. CONCLUSIONS This regimen showed outstanding clinical efficacy with acceptable tolerability for patients with resectable PDAC.
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Affiliation(s)
- Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
- Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan.
| | - Yutaka Takeda
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan
- Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan
| | - Hidenori Takahashi
- Department of Surgery, Osaka International Cancer Institute, Osaka, Japan
- Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan
| | - Shin Nakahira
- Department of Surgery, Sakai City Medical Center, Osaka, Japan
- Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan
| | - Masaki Kashiwazaki
- Department of Surgery, Osaka General Medical Center, Osaka, Japan
- Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan
| | - Junzo Shimizu
- Department of Surgery, Osaka Rosai Hospital, Osaka, Japan
- Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan
| | - Daisuke Sakai
- Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan
- Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan
| | - Fumiaki Isohashi
- Department of Radiation Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
- Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
- Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
- Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group, Osaka, Japan
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Bradley A, Van der Meer R, McKay CJ. A prognostic Bayesian network that makes personalized predictions of poor prognostic outcome post resection of pancreatic ductal adenocarcinoma. PLoS One 2019; 14:e0222270. [PMID: 31498836 PMCID: PMC6733484 DOI: 10.1371/journal.pone.0222270] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 08/19/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The narrative surrounding the management of potentially resectable pancreatic cancer is complex. Surgical resection is the only potentially curative treatment. However resection rates are low, the risk of operative morbidity and mortality are high, and survival outcomes remain poor. The aim of this study was to create a prognostic Bayesian network that pre-operatively makes personalized predictions of post-resection survival time of 12months or less and also performs post-operative prognostic updating. METHODS A Bayesian network was created by synthesizing data from PubMed post-resection survival analysis studies through a two-stage weighting process. Input variables included: inflammatory markers, tumour factors, tumour markers, patient factors and, if applicable, response to neoadjuvant treatment for pre-operative predictions. Prognostic updating was performed by inclusion of post-operative input variables including: pathology results and adjuvant therapy. RESULTS 77 studies (n = 31,214) were used to create the Bayesian network, which was validated against a prospectively maintained tertiary referral centre database (n = 387). For pre-operative predictions an Area Under the Curve (AUC) of 0.7 (P value: 0.001; 95% CI 0.589-0.801) was achieved accepting up to 4 missing data-points in the dataset. For prognostic updating an AUC 0.8 (P value: 0.000; 95% CI:0.710-0.870) was achieved when validated against a dataset with up to 6 missing pre-operative, and 0 missing post-operative data-points. This dropped to AUC: 0.7 (P value: 0.000; 95% CI:0.667-0.818) when the post-operative validation dataset had up to 2 missing data-points. CONCLUSION This Bayesian network is currently unique in the way it utilizes PubMed and patient level data to translate the existing empirical evidence surrounding potentially resectable pancreatic cancer to make personalized prognostic predictions. We believe such a tool is vital in facilitating better shared decision-making in clinical practice and could be further developed to offer a vehicle for delivering personalized precision medicine in the future.
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Affiliation(s)
- Alison Bradley
- Department of Management Science, Strathclyde Business School, University of Strathclyde, Glasgow, Scotland, United Kingdom
- West of Scotland Pancreatic Cancer Unit, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom
- * E-mail:
| | - Robert Van der Meer
- Department of Management Science, Strathclyde Business School, University of Strathclyde, Glasgow, Scotland, United Kingdom
| | - Colin J. McKay
- West of Scotland Pancreatic Cancer Unit, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom
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Han S, Choi SH, Choi DW, Heo JS, Han IW, Park DJ, Ryu Y. Neoadjuvant therapy versus upfront surgery for borderline-resectable pancreatic cancer. MINERVA CHIR 2019; 75:15-24. [PMID: 31115240 DOI: 10.23736/s0026-4733.19.07958-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Neoadjuvant therapy is recommended for patients with borderline-resectable pancreatic cancer (BRPC). In this study, we compare survival outcomes of neoadjuvant therapy with upfront surgery. METHODS From January 2011 to June 2016, 1415 patients underwent treatments for pancreatic cancer in Samsung Medical Center. Among them, 112 (7.9%) patients were categorized as BRPC by the NCCN 2016 guideline. They were classified by type of initial treatments into neoadjuvant group (NA, N.=26) and upfront surgery group (US, N.=86). RESULTS The median survival duration of all patients was 18.3 months. Patients in the NA group had more T4 disease than those in the US group (38.5% in NA versus 15.1% in the US group; P=0.010). Arterial involvement was more frequent in the NA group (42.3% versus 15.1%; P=0.003). In the NA group, ten (38.5%) patients underwent surgery, and seven of them had complete R0 resection. In the US group, 83 (96.5%) patients received radical surgery, and 42 (48.8%) had R0 resection. In survival analysis according to intent to treat, the overall two-year survival rate was 51.1% in the US group and 36.7% in the NA group (P=0.001). However, among patients who underwent surgery (N.=96), the two-year overall survival rate was not significantly different between the two groups (P=0.089). According to involved vessels, the survival rate was not different between patients with arterial or both arterial and venous involvement and in patients with only venous involvement (P=0.649). CONCLUSIONS It is necessary to demonstrate the efficacy of neoadjuvant therapy and to standardize the regimens through large-scale, multicenter, randomized controlled studies.
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Affiliation(s)
- Sunjong Han
- Departments of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
| | - Seong H Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea -
| | - Dong W Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jin S Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - In W Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Dae-Joon Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Youngju Ryu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Upfront Surgery versus Neoadjuvant Therapy for Resectable Pancreatic Cancer: Systematic Review and Bayesian Network Meta-analysis. Sci Rep 2019; 9:4354. [PMID: 30867522 PMCID: PMC6416273 DOI: 10.1038/s41598-019-40951-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 02/26/2019] [Indexed: 12/15/2022] Open
Abstract
Current treatment recommendations for resectable pancreatic cancer support upfront resection and adjuvant therapy. Randomized controlled trials offering comparison with the emerging neoadjuvant approach are lacking. This review aims to compare both treatment strategies for resectable pancreatic cancer. PubMed, MEDLINE, Embase, Cochrane Database and Cochrane Databases were searched for studies comparing neoadjuvant and surgery-first with adjuvant therapy for resectable pancreatic cancer. A Bayesian network meta-analysis was conducted using the Markov chain Monte Carlo method. Cochrane Collaboration’s risk of bias, ROBINS-I and GRADE tools were used to assess quality and risk of bias of included trials. 9 studies compared neoadjuvant therapy and surgery-first with adjuvant therapy (n = 22,285). Aggregate rate (AR) of R0 resection for neoadjuvant therapy was 0.8008 (0.3636–0.9144) versus 0.7515 (0.2026–0.8611) odds ratio (O.R.) 1.27 (95% CI 0.60–1.96). 1-year survival AR for neoadjuvant therapy was 0.7969 (0.6061–0.9500) versus 0.7481 (0.4848–0.8500) O.R. 1.38 (95% CI 0.69–2.96). 2-year survival AR for neoadjuvant therapy was 0.5178 (0.3000–0.5970) versus 0.5131 (0.2727–0.5346) O.R. 1.26 (95% CI 0.94–1.74). 5-year AR survival for neoadjuvant therapy was 0.2069 (0.0323–0.3300) versus 0.1783 (0.0606–0.2300) O.R. 1.19 (95% CI 0.65–1.73). In conclusion neoadjuvant therapy may offer benefit over surgery-first and adjuvant therapy. However, further randomized controlled trials are needed.
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Bradley A, Van Der Meer R. Neoadjuvant therapy versus upfront surgery for potentially resectable pancreatic cancer: A Markov decision analysis. PLoS One 2019; 14:e0212805. [PMID: 30817807 PMCID: PMC6394923 DOI: 10.1371/journal.pone.0212805] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 02/09/2019] [Indexed: 12/16/2022] Open
Abstract
Background Neoadjuvant therapy has emerged as an alternative treatment strategy for potentially resectable pancreatic cancer. In the absence of large randomized controlled trials offering a direct comparison, this study aims to use Markov decision analysis to compare efficacy of traditional surgery first (SF) and neoadjuvant treatment (NAT) pathways for potentially resectable pancreatic cancer. Methods An advanced Markov decision analysis model was constructed to compare SF and NAT pathways for potentially resectable pancreatic cancer. Transition probabilities were calculated from randomized control and Phase II/III trials after comprehensive literature search. Utility outcomes were measured in overall and quality-adjusted life months (QALMs) on an intention-to-treat basis as the primary outcome. Markov cohort analysis of treatment received was the secondary outcome. Model uncertainties were tested with one and two-way deterministic and probabilistic Monte Carlo sensitivity analysis. Results SF gave 23.72 months (18.51 QALMs) versus 20.22 months (16.26 QALMs). Markov Cohort Analysis showed that where all treatment modalities were received NAT gave 35.05 months (29.87 QALMs) versus 30.96 months (24.86QALMs) for R0 resection and 34.08 months (29.87 QALMs) versus 25.85 months (20.72 QALMs) for R1 resection. One-way deterministic sensitivity analysis showed that NAT was superior if the resection rate was greater than 51.04% or below 75.68% in SF pathway. Two-way sensitivity analysis showed that pathway superiority depended on obtaining multimodal treatment in either pathway. Conclusion Whilst NAT is a viable alternative to traditional SF approach, superior pathway selection depends on the individual patient’s likelihood of receiving multimodal treatment in either pathway.
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Affiliation(s)
- Alison Bradley
- Department of Management Science, Strathclyde Business School, University of Strathclyde, Glasgow, Scotland, United Kingdom
- West of Scotland Pancreatic Cancer Unit, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom
- * E-mail:
| | - Robert Van Der Meer
- Department of Management Science, Strathclyde Business School, University of Strathclyde, Glasgow, Scotland, United Kingdom
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12
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Xu JZ, Wang WQ, Zhang SR, Xu HX, Wu CT, Qi ZH, Gao HL, Li S, Ni QX, Yu XJ, Liu L. Neoadjuvant Therapy is Essential for Resectable Pancreatic Cancer. Curr Med Chem 2019; 26:7196-7211. [PMID: 29651946 DOI: 10.2174/0929867325666180413101722] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2017] [Revised: 12/26/2017] [Accepted: 04/04/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Awareness of the benefits of neoadjuvant therapy is increasing, but its use as an initial therapeutic option for patients with resectable pancreatic cancer remains controversial, especially for those patients without high-risk prognostic features. Even for patients with high-risk features who are candidates to receive neoadjuvant therapy, no standard regimen exists. METHODS In this review, we examined available data on the neoadjuvant therapy in patients with resectable pancreatic cancer, including prospective studies, retrospective studies, and ongoing clinical trials, by searching PubMed/MEDLINE, ClinicalTrials.gov, Web of Science, and Cochrane Library. The characteristics and results of screened studies were described. RESULTS Retrospective and prospective studies with reported results and ongoing randomized studies were included. For patients with resectable pancreatic cancer, neoadjuvant therapy provides benefits such as increased survival, decreased risk of comorbidities and mortality, and improved cost-effectiveness due to an increased completion rate of multimodal treatment. Highly active regimens such as FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) or gemcitabine plus nab-paclitaxel are considered acceptable therapeutic regimens. Additionally, platinum-containing regimens other than FOLFIRINOX are acceptable for selected patients. Other therapies, such as chemoradiation treatment, immuno-oncology agents, and targeted therapies are being explored and the results are highly anticipated. CONCLUSION This review highlights the benefits of neoadjuvant therapy for resectable pancreatic cancer. Some regimens are currently acceptable, but need more evidence from well-designed clinical trials or should be used after being carefully examined by a multidisciplinary team.
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Affiliation(s)
- Jin-Zhi Xu
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wen-Quan Wang
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shi-Rong Zhang
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Hua-Xiang Xu
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Chun-Tao Wu
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zi-Hao Qi
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - He-Li Gao
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shuo Li
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Quan-Xing Ni
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xian-Jun Yu
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Liang Liu
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Cullis J, Das S, Bar-Sagi D. Kras and Tumor Immunity: Friend or Foe? Cold Spring Harb Perspect Med 2018; 8:cshperspect.a031849. [PMID: 29229670 DOI: 10.1101/cshperspect.a031849] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
With the recent breakthroughs in immunotherapy as curative treatments in certain tumor types, there has been renewed interest in the relationship between immunity and tumor growth. Although we are gaining a greater understanding of the complex interplay of immune modulating components in the tumor microenvironment, the specific role that tumor cells play in shaping the immune milieu is still not well characterized. In this review, we focus on how mutant Kras tumor cells contribute to tumor immunity, with a specific focus on processes induced directly or indirectly by the oncogene.
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Affiliation(s)
- Jane Cullis
- Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016
| | - Shipra Das
- Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016
| | - Dafna Bar-Sagi
- Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016
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14
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Rahman SH, Urquhart R, Molinari M. Neoadjuvant therapy for resectable pancreatic cancer. World J Gastrointest Oncol 2017; 9:457-465. [PMID: 29290916 PMCID: PMC5740086 DOI: 10.4251/wjgo.v9.i12.457] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2017] [Revised: 08/24/2017] [Accepted: 09/16/2017] [Indexed: 02/05/2023] Open
Abstract
The use of neoadjuvant therapies has played a major role for borderline resectable and locally advanced pancreatic cancers (PCs). For this group of patients, preoperative chemotherapy or chemoradiation has increased the likelihood of surgery with negative resection margins and overall survival. On the other hand, for patients with resectable PC, the main rationale for neoadjuvant therapy is that the overall survival with current strategies is unsatisfactory. There is a consensus that we need new treatments to improve the overall survival and quality of life of patients with PC. However, without strong scientific evidence supporting the theoretical advantages of neoadjuvant therapies, these potential benefits might turn out not to be worth the risk of tumors progression while waiting for surgery. The focus of this paper is to provide the readers an overview of the most recent evidence on this subject.
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Affiliation(s)
| | - Robin Urquhart
- Department of Surgery, Dalhousie University, Halifax B3H 2Y9, Nova Scotia, Canada
| | - Michele Molinari
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States
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15
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Adjuvant or Neoadjuvant Therapy in the Treatment in Pancreatic Malignancies: Where Are We? Surg Clin North Am 2017; 98:95-111. [PMID: 29191281 DOI: 10.1016/j.suc.2017.09.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Since the advent of modern surgery for pancreatic cancer, clinicians have recognized this cancer's propensity to recur locally, metastasize, and cause death. Despite significant efforts to improve patient outcomes with better adjuvant therapy, only modest gains in survival have been observed. An alternative strategy of neoadjuvant therapy followed by surgery has the potential to improve patient selection and survival, and expand the pool of patients eligible for curative surgery. This article summarizes large, randomized trials of adjuvant therapy, explains the limitations imposed by up-front surgery, and suggests neoadjuvant therapy as a rational alternative to initial surgery and adjuvant therapy.
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16
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Zhan HX, Xu JW, Wu D, Wu ZY, Wang L, Hu SY, Zhang GY. Neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of prospective studies. Cancer Med 2017; 6:1201-1219. [PMID: 28544758 PMCID: PMC5463082 DOI: 10.1002/cam4.1071] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 03/12/2017] [Accepted: 03/13/2017] [Indexed: 12/13/2022] Open
Abstract
There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer (PC). However, study results have varied significantly. In this study, a systematic review and meta‐analysis of prospective studies were performed in order to evaluate safety and effectiveness of neoadjuvant therapy in PC. Thirty‐nine studies were selected (n = 1458 patients), with 14 studies focusing on patients with resectable disease (group 1), and 19 studies focusing on patients with borderline resectable and locally advanced disease (group 2). Neoadjuvant chemotherapy was administered in 97.4% of the studies, in which 76.9% was given radiotherapy and 74.4% administered with chemoradiation. The complete and partial response rate was 3.8% and 20.9%. The incidence of grade 3/4 toxicity was 11.3%. The overall resection rate after neoadjuvant therapy was 57.7% (group 1: 73.0%, group 2: 40.2%). The R0 resection rate was 84.2% (group 1: 88.2%, group 2: 79.4%). The overall survival for all patients was 16.79 months (resected 24.24, unresected 9.81; group 1: 17.76, group 2: 16.20). Our results demonstrate that neoadjuvant therapy has not been proven to be beneficial and should be considered with caution in patients with resectable PC. Patients with borderline resectable or locally advanced disease may benefit from neoadjuvant therapy, but further research is needed.
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Affiliation(s)
- Han-Xiang Zhan
- Department of General Surgery, Qilu hospital, Shandong University, Jinan, Shandong Province, 250012, China
| | - Jian-Wei Xu
- Department of General Surgery, Qilu hospital, Shandong University, Jinan, Shandong Province, 250012, China
| | - Dong Wu
- Department of General Surgery, Qilu hospital, Shandong University, Jinan, Shandong Province, 250012, China
| | - Zhi-Yang Wu
- Department of General Surgery, Qilu hospital, Shandong University, Jinan, Shandong Province, 250012, China
| | - Lei Wang
- Department of General Surgery, Qilu hospital, Shandong University, Jinan, Shandong Province, 250012, China
| | - San-Yuan Hu
- Department of General Surgery, Qilu hospital, Shandong University, Jinan, Shandong Province, 250012, China
| | - Guang-Yong Zhang
- Department of General Surgery, Qilu hospital, Shandong University, Jinan, Shandong Province, 250012, China
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17
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Li GJ, Ji JJ, Yang F, Xu HW, Bai Y. Preoperative lymphocyte-to-monocyte ratio predicts survival in primary hepatitis B virus-positive hepatocellular carcinoma after curative resection. Onco Targets Ther 2017; 10:1181-1189. [PMID: 28260933 PMCID: PMC5328305 DOI: 10.2147/ott.s110411] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Both inflammation and immunity are associated with the development of malignancy. The lymphocyte-to-monocyte ratio (LMR) has been confirmed as a prognostic factor for several malignant diseases. The purpose of our study was to analyze prognostic significance of preoperative LMR in hepatitis B virus (HBV)-related hepatocellular carcinoma after curative resection. Patients and methods A total of 253 patients with primary HBV-positive hepatocellular carcinoma who underwent a curative operation were enrolled in this retrospective study. The relationship between preoperative LMR and survival outcomes was analyzed through Kaplan–Meier curves and multivariate Cox regression analyses. Results Patients with a high LMR had a significantly higher mean overall survival than those with a low LMR (67 months vs 55 months, P=0.023), and high LMR remained significant for longer survival in the multivariate analysis (hazard ratio, 0.147; 95% confidence interval [CI]: 0.085–0.253; P=0.021). Furthermore, patients with a high LMR also had a higher median recurrence-free survival than those with a low LMR in univariate analyses (60 months vs 48 months, P=0.026) and multivariate analyses (hazard ratio, 0.317; 95% CI: 0.042–1.023; P=0.032). However, the survival benefit was limited to patients with advanced cancer. Conclusion LMR was confirmed as an independent prognostic biomarker for primary HBV-positive hepatocellular carcinoma after curative resection.
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Affiliation(s)
| | | | | | | | - Yu Bai
- Department of Pathology, The First Affiliated Hospital of Xin-Xiang Medical University, Henan, People's Republic of China
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18
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Hartwig W, Gluth A, Hinz U, Koliogiannis D, Strobel O, Hackert T, Werner J, Büchler MW. Outcomes after extended pancreatectomy in patients with borderline resectable and locally advanced pancreatic cancer. Br J Surg 2016; 103:1683-1694. [DOI: 10.1002/bjs.10221] [Citation(s) in RCA: 115] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2015] [Revised: 02/05/2016] [Accepted: 05/04/2016] [Indexed: 01/08/2023]
Abstract
Abstract
Background
In the recent International Study Group of Pancreatic Surgery (ISGPS) consensus on extended pancreatectomy, several issues on perioperative outcome and long-term survival remained unclear. Robust data on outcomes are sparse. The present study aimed to assess the outcome of extended pancreatectomy for borderline resectable and locally advanced pancreatic cancer.
Methods
A consecutive series of patients with primary pancreatic adenocarcinoma undergoing extended pancreatectomies, as defined by the new ISGPS consensus, were compared with patients who had a standard pancreatectomy. Univariable and multivariable analysis was performed to identify risk factors for perioperative mortality and characteristics associated with survival. Long-term outcome was assessed by means of Kaplan–Meier analysis.
Results
The 611 patients who had an extended pancreatectomy had significantly greater surgical morbidity than the 1217 patients who underwent a standard resection (42·7 versus 34·2 per cent respectively), and higher 30-day mortality (4·3 versus 1·8 per cent) and in-hospital mortality (7·5 versus 3·6 per cent) rates. Operating time of 300 min or more, extended total pancreatectomy, and ASA fitness grade of III or IV were associated with increased in-hospital mortality in multivariable analysis, whereas resections involving the colon, portal vein or arteries were not. Median survival and 5-year overall survival rate were reduced in patients having extended pancreatectomy compared with those undergoing a standard resection (16·1 versus 23·6 months, and 11·3 versus 20·6 per cent, respectively). Older age, G3/4 tumours, two or more positive lymph nodes, macroscopic positive resection margins, duration of surgery of 420 min or above, and blood loss of 1000 ml or more were independently associated with decreased overall survival.
Conclusion
Extended resections are associated with increased perioperative morbidity and mortality, particularly when extended total pancreatectomy is performed. Favourable long-term outcome is achieved in some patients.
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Affiliation(s)
- W Hartwig
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General, Visceral and Transplantation Surgery, University of Munich, Munich, Germany
| | - A Gluth
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General, Visceral and Transplantation Surgery, University of Munich, Munich, Germany
| | - U Hinz
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - D Koliogiannis
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General, Visceral and Transplantation Surgery, University of Munich, Munich, Germany
| | - O Strobel
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - T Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - J Werner
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General, Visceral and Transplantation Surgery, University of Munich, Munich, Germany
| | - M W Büchler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
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19
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de Geus SWL, Evans DB, Bliss LA, Eskander MF, Smith JK, Wolff RA, Miksad RA, Weinstein MC, Tseng JF. Neoadjuvant therapy versus upfront surgical strategies in resectable pancreatic cancer: A Markov decision analysis. Eur J Surg Oncol 2016; 42:1552-60. [PMID: 27570116 DOI: 10.1016/j.ejso.2016.07.016] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Revised: 07/10/2016] [Accepted: 07/21/2016] [Indexed: 12/18/2022] Open
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.
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Affiliation(s)
- S W L de Geus
- Surgical Outcomes Analysis & Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Surgery, 330 Brookline Avenue, Boston, MA 02215, USA.
| | - D B Evans
- Department of Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
| | - L A Bliss
- Surgical Outcomes Analysis & Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Surgery, 330 Brookline Avenue, Boston, MA 02215, USA.
| | - M F Eskander
- Surgical Outcomes Analysis & Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Surgery, 330 Brookline Avenue, Boston, MA 02215, USA.
| | - J K Smith
- Surgical Outcomes Analysis & Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Surgery, 330 Brookline Avenue, Boston, MA 02215, USA.
| | - R A Wolff
- Department of Gastrointestinal Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
| | - R A Miksad
- Surgical Outcomes Analysis & Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Surgery, 330 Brookline Avenue, Boston, MA 02215, USA.
| | - M C Weinstein
- Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
| | - J F Tseng
- Surgical Outcomes Analysis & Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Surgery, 330 Brookline Avenue, Boston, MA 02215, USA.
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Lee JC, Ahn S, Paik KH, Kim HW, Kang J, Kim J, Hwang JH. Clinical impact of neoadjuvant treatment in resectable pancreatic cancer: a systematic review and meta-analysis protocol. BMJ Open 2016; 6:e010491. [PMID: 27016245 PMCID: PMC4809107 DOI: 10.1136/bmjopen-2015-010491] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Revised: 02/15/2016] [Accepted: 03/01/2016] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Although the only curative strategy for pancreatic cancer is surgical resection, up to 85% of patients relapse after surgery. The efficacy of neoadjuvant treatment in resectable pancreatic cancer (RPC) remains unclear and there is no systematic review focusing fully on this issue. Recently, two prospective trials of neoadjuvant treatment in RPC were terminated early because of slow recruiting and existing randomised controlled trials (RCTs) have too small sample sizes. Therefore, to overcome probable biases, it would be more reasonable to include both RCTs and non-randomised studies (NRSs) with selected criteria. This review aims to investigate the effect of neoadjuvant chemotherapy (CTx) and chemoradiation therapy (CRT) in RPC using RCTs and specific NRSs. METHOD AND ANALYSIS This systematic review will include conventional RCTs as group I, and quasi-randomised controlled trials, non-randomised controlled trials and prospective cohort studies as group II. Two groups will be assessed and analysed separately. Comprehensive literature search will use Medline, Embase, Cochrane library and Scopus databases. Additionally, we will search references from relevant studies and abstracts from major conferences. Two authors will independently identify, screen, include studies, extract data and assess the risk of bias. Discrepancies will be resolved by consensus with another author. An independent methodologist will categorise and assess NRSs to minimise heterogeneity. In each study group, meta-analysis will be conducted using a random-effect model and statistical heterogeneity will be evaluated using I(2)-statistics. Publication bias will be visualised with contour-enhanced funnel plots and analysed with Egger's test. In group I, cumulative meta-analysis will be considered because the CTx regimen and CRT protocol have changed. The quality of evidence will be summarised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. ETHICS AND DISSEMINATION This review does not use primary data, and formal ethical approval is not required. Findings will be disseminated through peer-reviewed journals and committee conferences. TRIAL REGISTRATION NUMBER CRD42015023820.
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Affiliation(s)
- Jong-chan Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Soyeon Ahn
- Department of Biostatistics, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kyu-hyun Paik
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyoung Woo Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jingu Kang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jaihwan Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Li GJ, Xu HW, Ji JJ, Yang F, Gao BQ. Prognostic value of preoperative lymphocyte-to-monocyte ratio in pancreatic adenocarcinoma. Onco Targets Ther 2016; 9:1085-92. [PMID: 27042101 PMCID: PMC4780182 DOI: 10.2147/ott.s96707] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Inflammation and immunity have an important role in the development of cancer. The lymphocyte-to-monocyte ratio (LMR) has been shown to be of prognostic value in several malignant forms. The purpose of this study was to analyze the prognostic significance of preoperative LMR in post-curative resection of pancreatic adenocarcinoma. METHODS A total of 144 patients with primary pancreatic adenocarcinoma who underwent curative operation were enrolled in this retrospective study. The correlation between preoperative LMR and survival was analyzed using Kaplan-Meier curves and multivariate Cox regression analyses. RESULTS In the univariate analysis, an elevated preoperative LMR was significantly associated with an increased overall survival (OS) (19 months vs 12 months, P=0.000), and this result remained significant in the multivariate analysis (hazard ratio [HR]: 0.148; 95% confidence interval [CI]: 0.085-0.252; P=0.000). Furthermore, patients with high LMR also had higher median recurrence-free survival (RFS) than patients with low LMR in univariate (18 months vs 10 months, P=0.000) and multivariate analyses (HR: 0.148; 95% CI: 0.085-0.252; P=0.000). Subgroup analyses showed that both patients with stage III cancer and patients with stage I+II cancer can obtain OS and RFS benefits from high LMR. CONCLUSION LMR can be considered as an independent prognostic biomarker for operable pancreatic adenocarcinoma.
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Affiliation(s)
- Guang-Jun Li
- First Department of General Surgery, First Affiliated Hospital of Xin-Xiang Medical University, Henan, People's Republic of China
| | - Hong-Wei Xu
- First Department of General Surgery, First Affiliated Hospital of Xin-Xiang Medical University, Henan, People's Republic of China
| | - Juan-Juan Ji
- Department of Gastroenterology, First Affiliated Hospital of Xin-Xiang Medical University, Henan, People's Republic of China
| | - Fang Yang
- Department of Gastroenterology, First Affiliated Hospital of Xin-Xiang Medical University, Henan, People's Republic of China
| | - Bao-Qin Gao
- First Department of General Surgery, First Affiliated Hospital of Xin-Xiang Medical University, Henan, People's Republic of China
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Eskander MF, Bliss LA, Tseng JF. Pancreatic adenocarcinoma. Curr Probl Surg 2016; 53:107-54. [DOI: 10.1067/j.cpsurg.2016.01.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Accepted: 01/04/2016] [Indexed: 12/17/2022]
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