Postoperative Adjuvant Therapy for Resectable Pancreatic Cancer With Gemcitabine and Adoptive Immunotherapy

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.

Download Full-text

Are We Sure that Adjuvant Chemotherapy is the Best Approach for Resectable Pancreatic Cancer? Are We in the Era of Neoadjuvant Treatment? A Review of Current Literature

Journal of Clinical Medicine ◽

10.3390/jcm8111922 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1922 ◽

Cited By ~ 3

Author(s):

Oneda ◽

Zaniboni

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Chemotherapy ◽

Adjuvant Therapy ◽

Performance Status ◽

Neoadjuvant Treatment ◽

Early Recurrence ◽

Current Treatment ◽

R0 Resection ◽

Resectable Pancreatic Cancer ◽

Advantages And Disadvantages

The outcome of pancreatic cancer is poor, with a 9% 5-year survival rate. Current treatment recommendations in the 10%–20% of patients who present with resectable disease support upfront resection followed by adjuvant therapy. Until now, only early complete surgical (R0) resection and adjuvant chemotherapy (AC) with either FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) or nab-paclitaxel plus gemcitabine have been shown to prolong the survival. However, up to 30% of patients do not receive adjuvant therapy because of the development of early recurrence, postoperative complications, comorbidities, and reduced performance status. The aims of neoadjuvant chemotherapy (NAC) are to identify rapidly progressing patients to avoid futile surgery, eliminate micrometastases, increase the feasibility of R0 resection, and ensure the completion of multimodal treatment. Neoadjuvant treatments are effective, but there is no consensus on their use in resectable pancreatic cancer (RPC) because of its lack of a survival benefit over adjuvant therapy. In this review, we analyze the advantages and disadvantages of the two therapeutic approaches in RPC. We need studies that compare the two approaches and can identify the appropriate sequence of adjuvant therapy after neoadjuvant treatment and surgery.

Download Full-text

Comparison of neoadjuvant and adjuvant therapy for resectable pancreatic cancer using Markov decision modeling.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.448 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 448-448

Author(s):

Minsig Choi ◽

Sayaka Ishizawa ◽

Yan Liang ◽

Sina Rashidian ◽

Aaron R. Sasson ◽

...

Keyword(s):

Pancreatic Cancer ◽

Clinical Trials ◽

Neoadjuvant Chemotherapy ◽

Life Expectancy ◽

Adjuvant Therapy ◽

Clinical Outcome ◽

Resectable Pancreatic Cancer ◽

Cancer Data ◽

Study Results ◽

Quality Adjusted Life

448 Background: Meta-analysis of smaller studies have shown that neoadjuvant chemotherapy is more beneficial for patients with resectable pancreatic cancer than upfront surgery by comparing life expectancy (LE) and quality-adjusted life expectancy (QALE) computed from Markov models. The study results utilized literature data using several small clinical trials but no individual patient data was used and only gemzar based therapy was studied. Methods: Markov model was used to calculate the LE and QALE for adjuvant and neoadjuvant chemotherapy and individual patient parameters was used in the model to refine certain clinical outcome datapoints. We used 278 patients pancreatic cancer data from 2008 to 2017 from Stony Brook University and used the literature data from randomized clinical trials studying gemzar (GEM), gemzar and capecitabine (GEM+CAP) and modified FOLFIRINOX (mFOL). The median OS for each model was obtained by computer simulation. Results: Intensive adjuvant chemotherapy using mFOL had best simulation outcome with median OS (52.5 months), LE (81.5 months), and QALE (65.0 quality-adjusted life months) compared to using GEM (40.5, 66.5, and 52.9 months for median OS, LE, and QALE), GEM+CAP (16.5, 28.0, and 21.9 months for median OS, LE, and QALE), and 5-FU (16.5, 26.9, and 21.1 months for median OS, LE, and QALE). The neoadjuvant chemotherapy approach improved LE and QALE but not in median OS when compared to adjuvant therapy. Conclusions: Mathematical modeling confirms the improved clinical outcome for modified FOLFIRINOX in resectable pancreatic cancer. The benefit of neoadjuvant chemotherapy approach suggest further clinical trials are needed to determine the better treatment strategy for pancreatic cancer patients.

Download Full-text

Benefit of postoperative adjuvant therapy for pancreatic cancer

Cancer ◽

10.1002/cncr.24269 ◽

2009 ◽

Vol 115 (11) ◽

pp. 2420-2429 ◽

Cited By ~ 11

Author(s):

Kimberly A. Vanderveen ◽

Steven L. Chen ◽

Daixin Yin ◽

Rosemary D. Cress ◽

Richard J. Bold

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Postoperative Adjuvant Therapy

Download Full-text

Neoadjuvant vs Adjuvant Therapy for Resectable Pancreatic Cancer: The Evolving Role of Radiation

Seminars in Radiation Oncology ◽

10.1016/j.semradonc.2013.11.002 ◽

2014 ◽

Vol 24 (2) ◽

pp. 113-125 ◽

Cited By ~ 9

Author(s):

Sarah Hoffe ◽

Nikhil Rao ◽

Ravi Shridhar

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Resectable Pancreatic Cancer

Download Full-text

Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer

PLoS ONE ◽

10.1371/journal.pone.0010630 ◽

2010 ◽

Vol 5 (5) ◽

pp. e10630 ◽

Cited By ~ 207

Author(s):

Jin-Hyeok Hwang ◽

Johannes Voortman ◽

Elisa Giovannetti ◽

Seth M. Steinberg ◽

Leticia G. Leon ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Clinical Outcome ◽

Resectable Pancreatic Cancer

Download Full-text

Clinical experience with gemcitabine as postoperative adjuvant therapy in localized advanced pancreatic cancer?A preliminary report

Journal of Gastrointestinal Surgery ◽

10.1016/j.gassur.2005.01.276 ◽

2005 ◽

Vol 9 (4) ◽

pp. 615-616

Author(s):

T MISAWA ◽

Y UNEMURA ◽

T YOKOTA ◽

T OKUBO ◽

Y ISHIDA ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Clinical Experience ◽

Preliminary Report ◽

Advanced Pancreatic Cancer ◽

Postoperative Adjuvant Therapy

Download Full-text

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.

Download Full-text