Analysis of Predictors of Resection and Survival in Locally Advanced Stage III Pancreatic Cancer: Does the Nature of Chemotherapy Regimen Influence Outcomes?

Bednar, Filip; Zenati, Mazen S.; Steve, Jennifer; Winters, Sharon; Ocuin, Lee M.; Bahary, Nathan; Hogg, Melissa E.; Zeh, Herbert J.; Zureikat, Amer H.

doi:10.1245/s10434-016-5707-0

Cited by 47 publications

(45 citation statements)

References 28 publications

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“…Preoperative serum CA 19‐9 level was a prognostic factor for DFS. Bednar et al reported that radiation, ≧2 lines of chemotherapy, and surgery were significant independent prognostic factors for OS in 92 patients with initial UR‐LA (20% resectability). However, CA19‐9 level was not included in the multivariate analysis.…”

Section: Resultsmentioning

confidence: 99%

Surgical indication for and desirable outcomes of conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma

Satoi

Yamamoto

Yamaki

et al. 2019

Annals of Gastroent Surgery

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Aim of this review is to propose an acceptable surgical indication for conversion surgery in patients with initially unresectable (UR) pancreatic ductal adenocarcinoma (PDAC) by considering desirable outcomes, including resectability, overall survival (OS), and disease-free survival (DFS). A comprehensive literature search of PubMed was conducted through July 15, 2019. Eligible studies were those reporting on patients with UR-PDAC who underwent surgery. We excluded case reports with fewer than 10 patients, insufficient descriptions of survival data, and palliative surgery.When patients with UR-PDAC with no progression after chemo(radiation) therapy were offered surgical exploration, resectability and median survival time (MST) of those who underwent conversion surgery ranged from 20% to 69% (median, 52%) and from 19.5 to 33 months (median, 21.9 months), respectively. When conversion surgery was carried out in patients with expected margin-negative resection or with clinical response by Response Evaluation Criteria In Solid Tumors (RECIST), resectability and MST ranged from 18% to 27% (median, 20%) and from 21 to 35.3 months (median, 30 months), respectively. Among patients who underwent conversion surgery based on clinical response and decreased CA19-9 level after multimodal treatment, resectability and MST ranged from 2% to 24% (median, 4.1%) and from 24.1 to 64 months (median, 36 months), respectively. Decreased CA19-9 level was a predictor of resectability, OS and DFS by multivariate analysis. In conclusion, decision-making for conversion surgery based on clinical response and decreased CA19-9 level after multimodal treatment may be appropriate. With regard to desirable outcomes of OS and DFS, conversion surgery may provide improved survival for patients with initial UR-PDAC. K E Y W O R D Sconversion surgery, overall survival, resectability, surgical indication, unresectable pancreatic ductal adenocarcinoma | 7 SATOI eT Al.

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Section: Resultsmentioning

confidence: 99%

Surgical indication for and desirable outcomes of conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma

Satoi

Yamamoto

Yamaki

et al. 2019

Annals of Gastroent Surgery

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“…Systemic therapy for advanced pancreatic adenocarcinoma (including metastatic disease) has improved with the availability of more effective chemotherapeutic regimens such as FOLFIRINOX (median OS 11.1 months, RR 31.6%) and gemcitabine with nab-paclitaxel (median OS 8.5 months, RR 23%). [ 9 , 10 ] Advances in the chemotherapeutic treatment of metastatic pancreatic adenocarcinoma have been extrapolated to other potentially resectable categories of pancreatic adenocarcinoma [ 9 – 15 ]. More aggressive multimodality treatments have been employed for the management of resectable and borderline resectable tumors in addition to locally advanced tumors [ 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients

et al. 2017

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BackgroundRecent years have seen standardization of the anatomic definitions of pancreatic adenocarcinoma, and increasing utilization of neoadjuvant therapy (NAT). The aim of the current review was to summarize the evidence for NAT in pancreatic adenocarcinoma since 2009, when consensus criteria for resectable (R), borderline resectable (BR), and locally advanced (LA) disease were endorsed.MethodsPubMed search was undertaken along with extensive backward search of the references of published articles to identify studies utilizing NAT for pancreatic adenocarcinoma. Abstracts from ASCO-GI 2014 and 2015 were also searched.ResultsA total of 96 studies including 5520 patients were included in the final quantitative synthesis. Pooled estimates revealed 36% grade ≥ 3 toxicities, 5% biliary complications, 21% hospitalization rate and low mortality (0%, range 0–16%) during NAT. The majority of patients (59%) had stable disease. On an intention-to-treat basis, R0-resection rates varied from 63% among R patients to 23% among LA patients. R0 rates were > 80% among all patients who were resected after NAT. Among R and BR patients who underwent resection after NAT, median OS was 30 and 27.4 months, respectively.ConclusionsThe current study summarizes the recent literature for NAT in pancreatic adenocarcinoma and demonstrates improving outcomes after NAT compared to those historically associated with a surgery-first approach for pancreatic adenocarcinoma.Electronic supplementary materialThe online version of this article (10.1186/s12957-017-1240-2) contains supplementary material, which is available to authorized users.

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“…24 FFX and GEM plus nab-paclitaxel are now considered standard first line treatment options in metastatic pancreatic cancer. 2,25,26 However, FFX has been reported to have a stronger adverse effect than nab-paclitaxel. 24 In the present study, tumors shrunk by 80% upon administration of FFX twice.…”

Section: Discussionmentioning

confidence: 99%

Targeting claudin‐4 enhances chemosensitivity of pancreatic ductal carcinomas

et al. 2019

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Claudin (CLDN) family comprises of protein that form a tight junction, and is involved in regulating polarity and differentiation of cells. Here, we aimed to investigate the effects of inhibiting CLDN4 in pancreatic ductal carcinomas (PDC). We first examined 91 cases of human PDC by immunohistochemistry and found that CLDN4 expression was correlated with tumor invasion, nodal metastasis, and distant metastasis. Anti‐CLDN4 extracellular domain antibody, previously established by us (4D3), inhibited the proliferation of MIA‐PaCa‐2 PDC cells and increased intracellular 5‐fluorouracil (5‐FU) concentration with lowering transepithelial electrical resistance. Concurrent treatment of 5‐FU and 4D3 resulted in synergistic inhibition of growth of MIA‐PaCa‐2 cells in nude mice. In addition, MIA‐PaCa‐2 cell tumors treated with full‐dose folfirinox (FFX) decreased tumor diameters to 50%; however, 60% of mice were dead from adverse effects. In contrast, half‐dose FFX concomitant with 4D3 treatment decreased tumors equivalent to full‐dose FFX, but without the adverse effects. These findings suggest that targeting CLDN4 might increase the effectiveness and safety of anticancer drug therapy in PDC.

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Analysis of Predictors of Resection and Survival in Locally Advanced Stage III Pancreatic Cancer: Does the Nature of Chemotherapy Regimen Influence Outcomes?

Abstract: In LAPC, use of FOLFIRNOX and/or gemcitabine/nab-paclitaxel is associated with improved survival compared with older chemotherapy regimens, regardless of eventual resection. Tumor location and relationship to certain vasculature are important determinants of resection in this cohort.

Cited by 47 publications

References 28 publications

Surgical indication for and desirable outcomes of conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma

Surgical indication for and desirable outcomes of conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma

Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients

Targeting claudin‐4 enhances chemosensitivity of pancreatic ductal carcinomas

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