Effectiveness of Adjuvant Therapy in Patients with Pancreatic Cancer Who Underwent Neoadjuvant Therapy

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

10.2310/7800.16076 ◽

2017 ◽

Author(s):

Gregory C Wilson ◽

Brent T Xia ◽

Syed A Ahmed

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Pancreatic Adenocarcinoma ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Pancreatic Cancer ◽

Treatment Strategies ◽

Ductal Adenocarcinoma ◽

Borderline Resectable

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

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Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-019-52167-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Yoon Suk Lee ◽

Jong-Chan Lee ◽

Se Yeol Yang ◽

Jaihwan Kim ◽

Jin-Hyeok Hwang

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Protocol Analysis ◽

Meta Analysis ◽

Statistical Significance ◽

Supporting Evidence ◽

Resectable Pancreatic Cancer ◽

Survival Gain ◽

Intention To Treat

Abstract The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and per-protocol analysis (PP)). In 14 studies, 2,699 and 6,992 patients were treated with NAT and US, respectively. Although PP analysis showed the survival gain of NAT (HR 0.72, 95% CI 0.68–0.76), ITT analysis did not show the statistical significance (HR 0.96, 95% CI 0.82–1.12). However, NAT completed with subsequent surgery showed better survival over US completed with adjuvant therapy (HR 0.82, 95% CI 0.71–0.93). In conclusion, the supporting evidence for NAT in resectable PC was insufficient because the benefit was not demonstrated in ITT analysis. However, among the patients who completed both surgery and chemotherapy, NAT showed survival benefit over adjuvant therapy. Therefore, NAT could have a role of triaging the patients for surgery even in resectable PC.

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Is farnesyltransferase inhibitor effective as adjuvant or neoadjuvant therapy in orthotopic implantation of hamster pancreatic cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14153 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14153-14153

Author(s):

E. M. Lima ◽

C. Y. Morioka ◽

F. P. Costa ◽

S. Saito ◽

C. C. Huang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Surgical Resection ◽

Positive Control ◽

Histopathological Analysis ◽

Farnesyltransferase Inhibitor ◽

Partial Pancreatectomy ◽

P21 Ras ◽

Subsequent Activation

14153 Background: p21-Ras participates in signalling events from membrane tyrosine kinase receptors and a variety of intracellular biochemical pathways to downstream therapeutic strategy.Farnesyl transferase inhibitors (FTI) block the main post-translational plasma membrane and subsequent activation of downstream effector.A curative resection model in Syrian golden hamsters has been developed previously. Aim: To evaluate the effectiveness of FTI as adjuvant or neoadjuvant therapy in hamster experimental pancreatic cancer model. Materials and Methods: HaPT-1,a cell line derived from nitrosamine induced pancreatic cancer was used in these experiments.MTT and MTT agarose were performed.Subcutaneous implanted tumor was resected in exponential phase and tissue was implanted into the pancreas.At Day 7 or Day 14, partial pancreatectomy and splenectomy were performed.Hamsters were divided in 7 groups:1.Positive control (PC,n=5),2.Only FTI (FT,n=5),3.Neodjuvant therapy after surgical resection at Day 7 (NT-R7,n=10),4.Adjuvant therapy after resection at Day 7 (AT-S7,n=10),5.Neoadjuvant therapy after resection at Day 7 (NT-S14,n=10),6.Adjuvant therapy after resection at Day 14 (AT-S14,n=10), and 7.Only surgery at Day 14 (SR,n=5).FTI was administered for one week. In FT and NT groups, drug was administered 3 days after orthotopic implantation.Body weight and side effects were recorded.Fourteen days after the surgical resection, sacrifice was done.Four animals of each group were left to study the survival.After 180 days, living hamsters were sacrificed. Resected and necropsied specimens were sent to histopathological analysis. Results: Successful rate of implantation was 100%.PC,FT,NT-S7,AT-S7,NT-S14,AT-S14,and SR survived in average 82,103,119,134,123,132,and 139 days.Two hamsters of AT-S7 (20%),two of AT-S14 (20%),and two of SR (40%) were alive until 180 days.Intra operatory bleeding was higher in NT groups.Loss of body weight was present in all FTI treated groups. Conclusions: Farnesyltransferase inhibitor showed not to be effective in the curative treatment of orthotopically implanted tumors. It may be used to increase the survival time as adjuvant therapy. No significant financial relationships to disclose.

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Survival impact of neoadjuvant therapy in resected pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.367 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 367-367

Author(s):

Katelin Anne Mirkin ◽

Christopher S Hollenbeak ◽

Joyce Wong

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Median Survival ◽

Clinical Stage ◽

Stage I ◽

Median Income ◽

Stage Disease ◽

Surgery First ◽

The Impact

367 Background: Pancreatic cancer carries a dismal prognosis, with surgical resection and adjuvant therapy offering the only hope for long-term survival. In recent years, neoadjuvant therapy (NAT) has been employed to optimize outcomes. This study evaluates the impact of NAT on survival in patients with resected stage I-III pancreatic cancer. Methods: The National Cancer Data Base (2003-2011) was analyzed for patients with clinical stage I-III resected carcinoma of the pancreas who underwent NAT or surgery first +/- adjuvant therapy. Univariate statistics were used to compare characteristics between groups. Analysis of variance and Kaplan Meier analyses were used to compare median survival for each clinical stage of disease. Multivariate analyses were performed using a Cox proportional hazards model. Results: 16,122 patients who underwent NAT and 16,869 patients who underwent surgery-first were included. Patients who underwent NAT tended to be younger, covered by private insurance, have a higher median income, greater comorbidities, higher clinical stage disease, and undergo a whipple. Additionally, NAT patients had a greater number of positive regional lymph nodes (9 vs. 6, respectively), although a similar number of nodes retrieved, and higher pathological stage disease. In patients with clinical stage I disease, adjuvant therapy was associated with improved median survival than NAT and surgery-alone (24.8, 18.5, 17.9 months, p < 0.0001, respectively). However, in stage II, adjuvant and NAT offered similar median survival, which was improved over surgery-alone (20.5, 20.1, and 12.4 months, p < 0.0001, respectively). In stage III, NAT had improved median survival than the other groups (19.6, 14.2, 8.6 months, p < 0.0001, respectively). In the multivariate survival analysis, patients who received NAT had a 22% lower hazard of mortality up to 5 years as compared to adjuvant therapy (p < 0.0001). Conclusions: Neoadjuvant therapy in advanced stage pancreatic cancer confers a survival benefit and may allow more patients to undergo surgery; NAT appears to offer similar survival as adjuvant therapy in early stage pancreatic cancer.

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Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

10.2310/cgso.16076 ◽

2017 ◽

Author(s):

Gregory C Wilson ◽

Brent T Xia ◽

Syed A Ahmed

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Pancreatic Adenocarcinoma ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Pancreatic Cancer ◽

Treatment Strategies ◽

Ductal Adenocarcinoma ◽

Borderline Resectable

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

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Propensity score matched analysis of neoadjuvant therapy for resectable pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.381 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 381-381

Author(s):

Kenneth L Meredith ◽

Jamie Huston ◽

Anjan Jayantilal Patel ◽

Richard H. Brown ◽

Fadi Kayali ◽

...

Keyword(s):

Pancreatic Cancer ◽

Propensity Score ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Cancer Patients ◽

Tumor Size ◽

Survival Benefit ◽

Categorical Variables ◽

Resectable Pancreatic Cancer ◽

The Impact

381 Background: Neoadjuvant therapy (NT) for resectable pancreatic cancer continues to be debated. There is little data to demonstrate survival benefit over patients who were treated with up front surgery (UFS) vs NT. We sought to examine the impact of neoadjuvant chemotherapy (NCT), neoadjuvant chemoradiation (NCRT), and UFS on survival in pancreatic cancer patients. Methods: The NCDB was accessed to identify patients with pancreatic adenocarcinoma. Propensity score matching (PSM) was performed against age, tumor size, margin status, and institutional surgery volume. Patient characteristics (continuous and categorical variables) were compared using Mann-Whitney U, Kruskal Wallis and Pearson’s Chi-square test as appropriate. Survival analyses were performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) were developed to identify predictors of survival. All statistical tests were two-sided and α < 0.05 was considered significant. Results: After PSM, 5,034 patients (UFS 2,517; NT 2,517: 1,143 NCT and 1,374 NCRT) were included in the analysis. There was no difference in age, tumor size, or grade among cohorts. The mean nodes positive were 1.6 ± 2.6 in NT and 2 ± 3.3 in UFS, p = 0.02. In the pre-matched cohort R0 resections were performed in 75.9% UFS, 82.9% NCRT, and 79.6% NCT, p < 0.001. The median and 5 year survival for NCT, NCRT and UFS was 28.6 months and 25.2%, 25.7 months and 22.2%, and 21.3 months and 21.7%, p < 0.001. Adjuvant therapy (chemotherapy (CT) or CRT) in the UFS did demonstrate a survival benefit 22.5 months vs 18.6 months, p < 0.001, however this did not benefit NCT or NCRT, p = 0.8 and p = 0.8 respectively. Additionally survival in the UFS with adjuvant therapy either CT or CRT was still decreased compared to either NCT or NCRT, p < 0.001 and p = 0.001 respectively. MVA demonstrated that age, T-stage, lymph nodes positive, R0 resection, grade, NCT and NCRT were predictors of survival. Conclusions: Neoadjuvant therapy improves survival in resectable pancreatic cancer patients. NCT and NCRT demonstrated survival benefit compared to UFS even with adjuvant therapy. Patients with resectable pancreatic cancer should be considered for neoadjuvant therapy.

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