Essential role of radiation therapy for the treatment of pancreatic cancer

Dobiasch, Sophie; Goerig, Nicole L.; Fietkau, Rainer; Combs, Stephanie E.

doi:10.1007/s00066-017-1227-5

Cited by 23 publications

(5 citation statements)

References 64 publications

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“…The CONKO-007 study was designed to examine the value of radiotherapy in patients with nonmetastatic, unresectable pancreatic cancer [6,8,9]; radiotherapy has also been tested in other tumor entities [10,11]. The protocol stipulates that the resectability of each patient shall be assessed by a panel of five experienced pancreatic surgeons before inclusion in the study to exclude patients with initially resectable pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial

et al. 2020

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Purpose Chemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice. Methods One hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor. Results Following induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p < 0.001). Conclusion Tumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.

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Section: Introductionmentioning

confidence: 99%

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial

et al. 2020

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“…Nevertheless, neoadjuvant therapy consisting of chemotherapy and/or chemoradiation is routinely used in non-metastatic locally advanced pancreatic cancer (LAPC) that is initially deemed unresectable [11]. In selected patients who have a good response to neoadjuvant treatment and still no evidence of metastasis, surgical re-exploration with resection rates of 26% to 60% have been observed, which corresponds to more than a doubling of the median overall survival compared to unresected patients [12,13].…”

Section: Introductionmentioning

confidence: 99%

Cachectic Body Composition and Inflammatory Markers Portend a Poor Prognosis in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiation

Naumann

Eberlein

Farnia

et al. 2019

Cancers

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Background: Patients with pancreatic cancer often develop cancer cachexia, a complex multifactorial syndrome with weight loss, muscle wasting and adipose tissue depletion with systemic inflammation causing physical impairment. In patients with locally advanced pancreatic cancer (LAPC) neoadjuvant treatment is routinely performed to allow a subsequent resection. Herein, we assess body composition and laboratory markers for cancer cachexia both before and after neoadjuvant chemoradiation (CRT). Methods: Subcutaneous fat (SCF), visceral fat (VF), skeletal muscle (SM), weight and laboratory parameters were determined longitudinally in 141 LAPC patients treated with neoadjuvant CRT. Changes during CRT were statistically analyzed and correlated with outcome and Kaplan–Meier curves were plotted. Different prognostic factors linked to cachexia were assessed by uni- and multivariable cox proportional hazards models. Results: There was a significant decrease in weight as well as SCF, VF and SM during CRT. The laboratory parameter C-reactive protein (CRP) increased significantly, whereas there was a significant decrease in leukocyte count, hemoglobin, albumin and cholinesterase as well as in the tumor marker CA 19.9. Cachectic weight loss, sarcopenia, reductions in body compartments SCF, VF and SM, and changes in laboratory markers as well as resection affected survival in univariable analysis. In multivariable analysis, weight loss >5% (HR 2.8), reduction in SM >5% (HR 5.5), an increase in CRP (HR 2.2) or CA 19.9 (HR 1.9), and resection (HR 0.4) remained independently associated with survival, whereas classical cachexia and sarcopenia did not. Interestingly, the subgroup of patients with cachectic weight loss >5% or SM reduction >5% during CRT did not benefit from resection (median survival 12 vs. 27 months). Conclusions: Persistent weight loss and muscle depletion during CRT as well as systemic inflammation after CRT impacted survival more than cachexia or sarcopenia according classical definitions.

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“…Additionally, PARP inhibitors such as Olaparib, which target BRCA1/2 mutations, have demonstrated efficacy in clinical trials for patients with pancreatic cancer and have been approved by the FDA for this use ( 25 ). Although these have shown effectiveness in some clinical trials, drug resistance remains an issue ( 26 ). Patients with HER2 -overexpressing pancreatic cancer may respond to HER2-targeted therapies such as trastuzumab ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

The EFNA4 gene is a potential prognostic biomarker in pancreatic cancer: a bioinformatics analysis

Ye,

Chen,

Liu

et al. 2024

J Gastrointest Oncol

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Background Pancreatic cancer is a highly aggressive malignancy with poor prognosis, and there is an urgent need to understand its molecular mechanisms for early diagnosis and treatment. Despite surgical resection being the only effective treatment, most patients are diagnosed at an advanced stage, missing the optimal window for therapy. Identifying novel biomarkers is crucial for prognostic assessment, treatment planning, and early intervention. Ephrin A4 ( EFNA4 ), a member of the receptor tyrosine kinase family, is involved in vascular and epithelial development via regulation of cell migration and rejection. However, the role of EFNA4 in pancreatic cancer has not been reported. Therefore, our study aimed to clarify the role of EFNA4 in pancreatic cancer through bioinformatics analysis and vitro experiments. Methods The expression of EFNA4 and its potential value as a diagnostic and prognostic biomarker in pancreatic cancer was analyzed using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) database. According to the expression level of EFNA4 , patients were divided into high expression group and low expression group, and the correlation between overall survival (OS) and disease-free survival (DFS) with different expression levels of EFNA4 and clinical parameters were analyzed. Subsequently, reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect EFNA4 expression. The proliferation, invasion, and cloning ability of the cells were detected via Cell Counting Kit 8 (CCK8), Transwell, and plate cloning assays, respectively. Results EFNA4 is highly expressed in pancreatic cancer, and upregulation of EFNA4 is associated with poor prognosis. In this study, EFNA4 expression was correlated with T stage and TNM (tumor-node-metastasis) stage of pancreatic cancer, and the median survival time and progression-free survival (PFS) were worse in those with high EFNA4 expression (394 days) than in those with low expression (525 days) [hazard ratio (HR): 1.47, 95% confidence interval (CI): 1.00–2.16, P=0.047]. In addition, EFNA4 was also found to be involved in the regulation of signal pathways such as cell adhesion, cyclic AMP, insulin secretion, pancreatic secretion, and protein digestion and absorption. In vitro experiments demonstrated that EFNA4 knockdown significantly inhibited the proliferation, cloning ability, and invasiveness of the PANC-1 and SW1990 pancreatic cancer cell lines. Conclusions The abnormal expression of EFNA4 in pancreatic cancer is associated with p...

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Essential role of radiation therapy for the treatment of pancreatic cancer

Cited by 23 publications

References 64 publications

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial

Cachectic Body Composition and Inflammatory Markers Portend a Poor Prognosis in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiation

The EFNA4 gene is a potential prognostic biomarker in pancreatic cancer: a bioinformatics analysis

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