Better Defining the Role of Total Neoadjuvant Radiation: Changing Paradigms in Locally Advanced Pancreatic Cancer

Vidrí, Roberto J.; Vogt, Anne O; MacGillivray, Dougald C.; Bristol, Ian J.; Fitzgerald, Timothy L.

doi:10.1245/s10434-019-07584-5

Cited by 20 publications

(25 citation statements)

References 20 publications

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“…Furthermore, in the derivation cohort, the results of a multivariate Cox regression analysis revealed that postoperative chemotherapy and radiation were significant protective factors; however, lymph node metastasis was an independent risk factor for PDAC patients. This is accordance with the results of recent clinical cohort studies [33][34][35].…”

Section: Discussionsupporting

confidence: 93%

Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma

et al. 2020

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Background: Hypermethylation of gene promoters plays an important role in tumorigenesis. The present study aimed to identify and validate promoter methylation-driven genes (PMDGs) for pancreatic ductal adenocarcinoma (PDAC). Methods: Based on GSE49149 and the PDAC cohort of The Cancer Genome Atlas (TCGA), differential analyses of promoter methylation, correlation analysis, and Cox regression analysis were performed to identify PMDGs. The promoter methylation level was assessed by bisulfite sequencing polymerase chain reaction (BSP) in paired tumor and normal tissues of 72 PDAC patients. Kaplan−Meier survival analyses were performed to evaluate the clinical value of PMDGs. Results: In GSE49149, the β-value of the dipeptidyl peptidase like 6 (DPP6) promoter was significantly higher in tumor compared with normal samples (0.50 vs. 0.24, P<0.001). In the PDAC cohort of TCGA, the methylation level of the DPP6 promoter was negatively correlated with mRNA expression (r = −0.54, P<0.001). In a multivariate Cox regression analysis, hypermethylation of the DPP6 promoter was an independent risk factor for PDAC (hazard ratio (HR) = 543.91, P=0.002). The results of BSP revealed that the number of methylated CG sites in the DPP6 promoter was greater in tumor samples than in normal samples (7.43 vs. 2.78, P<0.001). The methylation level of the DPP6 promoter was moderately effective at distinguishing tumor from normal samples (area under ROC curve (AUC) = 0.74, P<0.001). Hypermethylation of the DPP6 promoter was associated with poor overall (HR = 3.61, P<0.001) and disease-free (HR = 2.01, P=0.016) survivals for PDAC patients. Conclusion: These results indicate that DPP6 promoter methylation is a potential prognostic biomarker for PDAC.

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Section: Discussionsupporting

confidence: 93%

Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma

et al. 2020

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“…Additionally, there was about 6.0-14.4% downstaging rate after chemoradiotherapy for LAPC [23][24][25], which was similar with that (9.3%) in our study. Nevertheless, chemoradiation did not confer a survival bene t compared with chemotherapy alone [23]. This may be ascribed to conventional fractionation of radiotherapy and relatively low dose.…”

Section: Discussionsupporting

confidence: 90%

“…In a previous study with review of The National Cancer Data Base, it was demonstrated that the addition of radiotherapy to neoadjuvant chemotherapy was associated with higher downstaging and complete pathologic response rates than chemotherapy alone [23]. Additionally, there was about 6.0-14.4% downstaging rate after chemoradiotherapy for LAPC [23][24][25], which was similar with that (9.3%) in our study. Nevertheless, chemoradiation did not confer a survival bene t compared with chemotherapy alone [23].…”

Section: Discussionsupporting

confidence: 89%

“…However, for the rest studies with systemic therapy alone, surgical resection was not performed and included in the nomogram [8,20,21]. In a previous study with review of The National Cancer Data Base, it was demonstrated that the addition of radiotherapy to neoadjuvant chemotherapy was associated with higher downstaging and complete pathologic response rates than chemotherapy alone [23]. Additionally, there was about 6.0-14.4% downstaging rate after chemoradiotherapy for LAPC [23][24][25], which was similar with that (9.3%) in our study.…”

Section: Discussionmentioning

confidence: 99%

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Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer after Chemoradiotherapy

Zhu

Liu

Cao

et al. 2020

Preprint

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Background: Due to common practice of hypofractionated radiotherapy in pancreatic cancer and heterogeneous chemotherapy regimens in previous studies, modified nomograms are required. Therefore, we aim to develop and validate prognostic nomograms for locally advanced pancreatic cancer (LAPC) after stereotactic body radiation therapy (SBRT) and chemotherapy.Methods: The development cohort comprised 925 patients with LAPC receiving SBRT and gemcitabine-based chemotherapy in our center, while 297 patients from another two centers formed the validation cohort. Nomograms were created from COX models and internally validated by bootstrap. Model discriminations were evaluated by calibration plots and concordance index (C-index). A decision curve analysis (DCA) was performed to evaluate clinical benefits of nomograms. Additionally, recursive partitioning analysis (RPA) was used for stratifications of survival probability based on the total score of each patient calculated by nomograms.Results: Weight loss, tumor diameter, radiation dose, CA19-9 kinetics after treatment and surgical resection were included in the nomogram for overall survival (OS), while the five factors plus performance status formed the nomogram for progression free survival (PFS). The corrected C-indexes for estimated 1-year and 2-year OS of the development cohort were 0.88 (95% CI: 0.85-0.91) and 0.86 (95% CI: 0.83-0.90). For those of the validation cohort, it was 0.88 (95% CI: 0.82-0.94) and 0.83 (95% CI: 0.74-0.91). Additionally, the corrected C-index for predicted 1-year PFS in the development and validation cohort was 0.83 (95% CI: 0.81-0.86) and 0.82 (95% CI: 0.78-0.87), respectively. The calibration plots showed good agreement of 1- and 2-year OS and 1-year PFS between the estimations and actual observations. Potential clinical benefits were demonstrated with DCA. Additionally, for 1- and 2-year OS and 1-year PFS, patients were stratified into four groups with different survival probability by RPA.Conclusion: The validated nomograms provided useful predictions of OS and PFS for LAPC with chemoradiotherapy.

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“…In a multicenter phase II trial in four hospitals in the Netherlands that enrolled 50 patients, stereotactic body radiotherapy was reported as feasible, and in 12% of the patients, a potentially curative resection could be performed [61]. In another retrospective cohort study, neoadjuvant radiotherapy was associated with increased pathologic downstaging and R0 resection rates [62].…”

Section: Long-term Survivalmentioning

confidence: 99%

Systematic review and meta-analysis of contemporary pancreas surgery with arterial resection

Rebelo

Büdeyri

Heckler

et al. 2020

Langenbecks Arch Surg

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Objective Advances in multimodality treatment paralleled increasing numbers of complex pancreatic procedures with major vascular resections. The aim of this meta-analysis was to evaluate the current outcomes of arterial resection (AR) in pancreatic surgery. Methods A systematic literature search was carried out from January 2011 until January 2020. MOOSE guidelines were followed. Predefined outcomes were morbidity, pancreatic fistula, postoperative bleeding and delayed gastric emptying, reoperation rate, mortality, hospital stay, R0 resection rate, and lymph node positivity. Duration of surgery, blood loss, and survival were also analyzed. Results Eight hundred and forty-one AR patients were identified in a cohort of 7111 patients. Morbidity and mortality rates in these patients were 66.8% and 5.3%, respectively. Seven studies (579 AR patients) were included in the meta-analysis. Overall morbidity (48% vs 39%, p = 0.1) and mortality (3.2% vs 1.5%, p = 0.27) were not significantly different in the groups with or without AR. R0 was less frequent in the AR group, both in patients without (69% vs 89%, p < 0.001) and with neoadjuvant treatment (50% vs 86%, p < 0.001). Weighted median survival was shorter in the AR group (18.6 vs 32 months, range 14.8–43.1 months, p = 0.037). Conclusions Arterial resections increase the complexity of pancreatic surgery, as demonstrated by relevant morbidity and mortality rates. Careful patient selection and multidisciplinary planning remain important.

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Better Defining the Role of Total Neoadjuvant Radiation: Changing Paradigms in Locally Advanced Pancreatic Cancer

Cited by 20 publications

References 20 publications

Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma

Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma

Development and Validation of Multicenter Predictive Nomograms for Locally Advanced Pancreatic Cancer after Chemoradiotherapy

Systematic review and meta-analysis of contemporary pancreas surgery with arterial resection

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