Neoadjuvant Treatment for Pancreatic Cancer

Raufi, Alexander G.; Manji, Gulam A.; Chabot, John A.; Bates, Susan E.

doi:10.1053/j.seminoncol.2018.12.002

Cited by 79 publications

(68 citation statements)

References 49 publications

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“…The health effect of this disease continues to escalate, as recent studies indicate PDAC will be the second leading cause of cancer-related mortality by 2030 (2). Surgical resection remains a patient's best chance at curative therapy when tumors are detected early (3). However, even in successfully resected patients, prognosis remains grim, with median overall survival estimated as less than 23 months (4).…”

Section: Introductionmentioning

confidence: 99%

“…However, even in successfully resected patients, prognosis remains grim, with median overall survival estimated as less than 23 months (4). As a result, surgical resection is often combined with chemotherapy and/or radiation therapy (3). While these conventional therapeutic modalities lead to modest improvement in overall survival, they are by no means curative in most individuals, emphasizing the need for improved therapeutic options.…”

Section: Introductionmentioning

confidence: 99%

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Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemotherapy and radiotherapy

Farren¹,

Sayegh²,

Ware³

et al. 2020

JCI Insight

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemotherapy and radiotherapy

Farren¹,

Sayegh²,

Ware³

et al. 2020

JCI Insight

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“…Several therapies focus on inactivating the checkpoint in order to force cells with excess DNA damage to proceed through mitosis and induce cell death. For example, the taxanes arrest cells at the G2M phase of the cell cycle that demonstrated significant impact against many solid tumors, such as gastric cancer [ 11 ], lung cancer [ 12 ], breast cancer [ 13 , 14 ], and pancreatic cancer [ 15 , 16 ]. Thus, we sought to quantify the amount of G2M checkpoint pathway activity.…”

Section: Introductionmentioning

confidence: 99%

High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection

Oshi

Newman

Tokumaru

et al. 2020

Cancers

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Pancreatic cancer is highly mortal due to uncontrolled cell proliferation. The G2M checkpoint pathway is an essential part of the cell cycle. We hypothesized that a high G2M pathway score is associated with cell proliferation and worse survival in pancreatic cancer patients. Gene set variation analysis using the Hallmark G2M checkpoint gene set was used as a score to analyze a total of 390 human pancreatic cancer patients from 3 cohorts (TCGA, GSE62452, GSE57495). High G2M score tumors enriched other cell proliferation genes sets as well as MKI67 expression, pathological grade, and proliferation score. Independent of other prognostic factors, G2M score was predictive of disease-specific survival in pancreatic cancer. High G2M tumor was associated with high mutation rate of KRAS and TP53 and significantly enriched these pathway gene sets, as well as high infiltration of Th2 cells. High G2M score consistently associated with worse overall survival in 3 cohorts, particularly in R1/2 resection, but not in R0. High G2M tumor in R1/2 highly enriched metabolic and cellular components’ gene sets compared to R0. To our knowledge, this is the first study to use gene set variation analysis as a score to examine the clinical relevancy of the G2M pathway in pancreatic cancer.

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“…The regimens used widely in clinical practice can be classified as gemcitabinebased (e.g., gemcitabine plus nab-paclitaxel, gemcitabine plus capecitabine) or 5-FU-based (e.g., full-dose or modified FOLFIRINOX and S-1 plus nab-paclitaxel). 27 Considering that different chemotherapy regimens may produce different therapeutic effects, we performed a subgroup analysis. Surprisingly, we found that patients who received gemcitabine-based NAC had more favorable OS than those underwent upfront resection, suggesting that gemcitabine-based regimens might be the first choice for RPC.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemotherapy for primary resectable pancreatic cancer: a systematic review and meta-analysis

Ye¹,

Zhang²,

Chen³

et al. 2020

HPB

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Background: Preoperative chemotherapy has shown benefits for locally advanced and borderline resectable pancreatic cancer. Neoadjuvant chemotherapy (NAC) has also been attempted in resectable pancreatic cancer (RPC); however, its role remains controversial. This study aimed to compare the clinical difference between NAC and upfront resection (UR) in RPC.Methods: Electronic databases including PubMed, Embase, Medline, Web of Science, ClinicalTrials. gov, and Cochrane Central Register of Controlled Trials were searched for relevant articles from inception to February 2019 that addressed the overall survival in patients with RPC treated with or without NAC to identify eligible studies. Eleven studies were included in the final meta-analysis. The quality assessment of the included studies was based on the Newcastle-Ottawa quality scale. Data of the unresectable rate, R0 resection rate, and positive lymph node rate were also extracted in each study for further analysis. Pooled hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CIs) were calculated to assess the strength of the association.Results: A total of eleven studies (eight cohort studies and three randomized controlled trials) involving 9773 patients were included. Ten of the eleven studies followed the "intention-to-treat" principle. NAC was found to be significantly associated with a higher R0 resection rate (P < 0.0001; OR = 2.62, 95% CI 1.70-4.03) and increased negative lymph node rate (P < 0.00001; OR = 0.34, 95% CI 0.31-0.37).However, compared with the UR group, NAC was related to a lower surgical resection rate (P = 0.0004; OR = 2.18, 95% CI 1.41-3.37). Overall, the NAC group exhibited no benefits in terms of overall survival compared with that in the UR group (P = 0.10; HR = 0.86, 95% CI 0.73-1.03). In the subgroup analysis, however, patients who received gemcitabine-based regimen as the NAC strategy had more favorable overall survival than that in the UR group (P = 0.04; HR = 0.75, 95% CI 0.57-0.99).Conclusions: NAC may be associated with a lower resection rate; however, it is associated with an increased R0 resection rate and lymph node negative rate. Although overall survival was similar in patients with or without NAC, gemcitabine-based NAC might provide longer overall survival. Further largevolume, randomized controlled trials are needed to validate the improved prognosis of patients undergoing NAC.

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Neoadjuvant Treatment for Pancreatic Cancer

Cited by 79 publications

References 49 publications

Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemotherapy and radiotherapy

Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemotherapy and radiotherapy

High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection

Neoadjuvant chemotherapy for primary resectable pancreatic cancer: a systematic review and meta-analysis

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