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

The results of treatment of localized (early) pancreatic cancer are unsatisfactory despite all achievements of modern clinical and surgical oncology. Nevertheless, certain success was achieved even in these extremely unfavorable patients regarding their prognosis. The authors analyzed evolution of adjuvant therapy, as well as new concepts in the treatment of borderline resectable and resectable pancreatic cancer. Modern anticancer therapy with acceptable toxicity profile significantly improved the outcomes. However, further research is needed to improve the effectiveness of treatment despite favorable current results.

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The Role of the Appleby Operation and Arterial Resection in the Multimodality Management of Borderline Resectable Pancreatic Cancer

Multimodality Management of Borderline Resectable Pancreatic Cancer ◽

10.1007/978-3-319-22780-1_16 ◽

2016 ◽

pp. 247-264 ◽

Cited By ~ 1

Author(s):

Ken-ichi Okada ◽

Hiroki Yamaue

Keyword(s):

Pancreatic Cancer ◽

Resectable Pancreatic Cancer ◽

Borderline Resectable ◽

Borderline Resectable Pancreatic Cancer ◽

Arterial Resection

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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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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.

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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.

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Role of para-aortic lymph node sampling in pancreatic cancer surgery.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.715 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 715-715

Author(s):

Yusuke Kazami ◽

Hiromichi Ito ◽

Yoshihiro Ono ◽

Takafumi Sato ◽

Yosuke Inoue ◽

...

Keyword(s):

Pancreatic Cancer ◽

Lymph Node ◽

Pancreatic Resection ◽

Pancreatic Head ◽

Imaging Study ◽

Resectable Pancreatic Cancer ◽

Lymph Node Sampling ◽

Aortic Lymph Node

715 Background: In the management of pancreatic cancer, para-aortic lymph node (PALN) metastasis is regarded as distant metastasis, and systemic treatment is recommended. However, imaging study is not perfect to detect all PALN metastasis and the management of intraoperatively discovered PALN has been controversial. We hypothesized that sampling of PALNs on exploration could allow us to avoid pancreatic resection for patients who would not benefit. In this study, we evaluated the incidence and the effect on the long-term outcomes for patients with potentially resectable pancreatic cancer. Methods: Three hundred and ninety-two patients who had PALNs sampled upon potentially resectable pancreatic cancer from 2005 through 2014 were included in the study. All patients were appropriately staged preoperatively with CT/MRI and those with suspected PALN metastasis were not considered as candidates for resection. The patients whose resections were aborted because of liver metastasis or peritoneal dissemination discovered on exploration, or those who died within 30-days after the operation were not included. Evaluated outcomes were incidence of PALN metastasis and their recurrence-free and overall survivals (RFS, OS). Results: The patients’ median age was 74 years, and 58.6% was man. 67.8% had tumors at pancreatic head. Preoperative chemotherapy was given only on 16 patients (3.2%). Among 392 patients with PALNs sampled, 53 (13.5%) patients had metastasis; Resection was completed on 40 patients and resection was aborted on the rest. Among patients who underwent pancreatic resection, median RFS and OS were 10 and 12 months for patients with PALN metastasis, compared to 17 and 26 months for those without PALN metastasis (p < 0.001 for RFS and p < 0.001 for OS). The 5-year-OS rates for patients with/without PALN metastasis were 5.9% and 25% (p < 0.001). Among 53 patients with PALN metastasis, OS were not different between the patients who underwent resection and those who did not (median 13 months vs 17 months, p = 0.06), and there were no recurrence-free survivors. Conclusions: PALN sampling and evaluation before committing to resection is useful to identify the patients who can unlikely benefit and to avoid unnecessary morbid operation.

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