Chemotherapy and radiation components of neoadjuvant treatment of pancreatic head adenocarcinoma: Impact on perioperative mortality and long-term survival

Franko, Jan; Hsu, Harold W.; Thirunavukarasu, Pragatheeshwar; Franková, Daniela; Goldman, Charles D.

doi:10.1016/j.ejso.2016.10.021

Cited by 21 publications

(17 citation statements)

References 28 publications

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“…While CFRT in addition to chemotherapy improved R0 resectability and improved tumor downstaging when compared to chemotherapy alone, no differences were observed in OS. These findings are concordant with another study utilizing the NCDB (2006)(2007)(2008)(2009)(2010)(2011), that similarly showed no OS benefit with the addition of CFRT to neoadjuvant chemotherapy [28]. Randomized trials are needed to identify the benefit of CFRT in the neoadjuvant setting, and we anticipate the results of the ongoing CONKO-007 and ESPAC-5F to more fully answer this question.…”

Section: Discussionsupporting

confidence: 84%

Neoadjuvant stereotactic body radiation therapy for nonmetastatic pancreatic adenocarcinoma

et al. 2019

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Background: Neoadjuvant therapy is a strategy for resectable and borderline resectable pancreatic cancer, but a consensus approach regarding optimal management is undetermined. Neoadjuvant options include chemotherapy with/without radiotherapy. Stereotactic body radiation therapy (SBRT) is a novel radiation technique that may provide benefit over conventionally fractionated radiation therapy (CFRT) in the neoadjuvant setting. The purpose of the present study is to determine neoadjuvant treatment with SBRT to other neoadjuvant treatment options for patients with resectable pancreatic cancer. Material and methods: The National Cancer Database was queried (2004-2015) for patients with nonmetastatic pancreatic adenocarcinoma receiving neoadjuvant therapy followed by pancreatectomy. Patients were categorized based on the type of neoadjuvant treatment administered. Statistics included temporal trend assessment by annual percent change (APC), predictors for SBRT by multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis without and with propensity matching, and Cox proportional hazards modeling for univariable OS analysis. Results: Of 5828 patients, 332 (5.7%), 3234 (55.5%) and 2262 (38.8%) received neoadjuvant chemo-SBRT, chemotherapy, and chemo-CFRT, respectively. SBRT utilization increased from 0% in 2004 to 9.5% in 2015, with a greater APC after 2010 (p < .001). SBRT was more likely to be utilized in patients with T3-4 and node-positive disease (p < .05 for all). The chemo-SBRT cohort was associated with a higher OS rate before and after propensity matching (p < .05 for both). The rate of R0 resection was higher in radiotherapy groups than the chemotherapy cohort (p < .001). Conclusions: Utilization of neoadjuvant SBRT for pancreatic cancer is increasing. In the neoadjuvant setting, chemo-SBRT may improve R0 resection and OS over chemotherapy and chemo-CFRT, although confirmatory prospective studies are needed for confirmation.

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Section: Discussionsupporting

confidence: 84%

Neoadjuvant stereotactic body radiation therapy for nonmetastatic pancreatic adenocarcinoma

et al. 2019

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“…2 Even after a successful pancreatic resection, prognosis is very poor with a 5-year survival of approximately 4-30% and a median survival of 18-29 months. [3][4][5][6] Pancreatoduodenectomy is a major abdominal operation, with a risk of major complications up to 57%. [7][8][9] Frequent postoperative complications include wound infection, delayed gastric emptying, pancreatic fistula and post-pancreatectomy haemorrhage.…”

Section: Introductionmentioning

confidence: 99%

Systematic review on the impact of pancreatoduodenectomy on quality of life in patients with pancreatic cancer

Dijk

Heerkens

Tseng

et al. 2018

HPB

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“…11 Similarly, other studies using data from the National Cancer Database (NCDB) have shown no difference in decreased overall survival for patients receiving chemoradiation compared with chemotherapy alone. [12][13][14] Furthermore, a meta-analysis demonstrated similar survival results and increased toxicity with chemoradiotherapy regimens. 15 Therefore, current retrospective series do not strongly favor the use of chemoradiotherapy to improve overall survival in PDAC.…”

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confidence: 87%

Editorial About: “A Prospective, Open-Label, Multicenter Phase II Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma”

2019

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Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that affected approximately 53,000 new patients in 2016. Patients with a diagnosis of this malignancy have a 5-year overall survival rate of 10%, which increases only to 25% for those with resectable disease. 1,2 These poor outcomes reflect two notions. First, PDAC is a systemic disease at the time of diagnosis regardless of clinical stage. As such, treatment must include systemic therapy as one component of the therapy. Second, despite progressive advances during the last several years, current treatment options have limited efficacy at reducing recurrences and disease progression.Historically, results from studies evaluating the use of radiotherapy for PDAC have been mixed, with adjuvant radiotherapy trials showing disparate results. 3,4 The report entitled ''A Prospective, Open-Label Multicenter Phase II Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent With Radiation for Resectable Pancreatic Ductal Adenocarcinoma'' described the role of neoadjuvant radiation (total dose, 50.4 Gy) given concurrently with full doses of chemotherapy (gemcitabine and S1). 5 The authors demonstrated an impressive median survival of 55 months for 63 patients who had resectable and borderline resectable tumors treated with this regimen. 5 This trial adds to the body of knowledge regarding the use of neoadjuvant chemoradiation in the treatment of pancreatic cancer. The unique aspect of this trial was full doses of chemotherapy delivered concurrently with radiation, thus targeting both local and distant disease.The results of this study should be taken in light of other recent trials. The PREOPANC-1 trial was a phase 3 trial that evaluated the role of preoperative chemoradiotherapy versus immediate surgery for 246 patients with resectable or borderline resectable tumors. 6 All the patients received 6 months of perioperative gemcitabine. Despite equal total doses of systemic chemotherapy, the trial demonstrated improvements in both median recurrencefree survival [median, 9.9 vs 7.7 months; hazard ratio (HR), 0.67; p = 0.010] and overall survival (median, 17.1 vs 13.5 months; HR, 0.71; p = 0.047) with the neoadjuvant chemoradiation approach. It is important to note that the patients in the chemoradiation arm of the study received 30% of all the systemic chemotherapy during the preoperative period. Moreover, this trial did not use the more active systemic regimens available currently.The randomized phase 2 and 3 Prep-02/JSAP-05 trial, which used the same chemotherapy regimen in the experimental arm as the current study used, compared the use of neoadjuvant chemotherapy with the use of upfront surgery followed by adjuvant S-1 chemotherapy. 7 The study demonstrated a significantly improved median overall survival of 36.7 months in the neoadjuvant therapy cohort versus 26.7 months in the upfront surgery cohort (p = 0.015), with a 2-year overall survival rate of 64% versus 53%. Therefore, the single-arm design of the current study begs the question re...

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Chemotherapy and radiation components of neoadjuvant treatment of pancreatic head adenocarcinoma: Impact on perioperative mortality and long-term survival

Cited by 21 publications

References 28 publications

Neoadjuvant stereotactic body radiation therapy for nonmetastatic pancreatic adenocarcinoma

Neoadjuvant stereotactic body radiation therapy for nonmetastatic pancreatic adenocarcinoma

Systematic review on the impact of pancreatoduodenectomy on quality of life in patients with pancreatic cancer

Editorial About: “A Prospective, Open-Label, Multicenter Phase II Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma”

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