Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer

332 Background: Pancreatic cancer is a disease primarily diagnosed in elderly patients; however, a significant number of young patients will also be affected. We hypothesized young patients with pancreatic cancer would be treated more aggressively and therefore have better prognosis. Methods: A retrospective review of a prospectively maintained cancer database was queried for all patients treated for pancreatic cancer at our institution. Age 50 years was selected to stratify pancreatic cancer patients as young or old. Results: Of 320 pancreatic cancer patients identified from the database, 56 (18%) were ≤ 50 years old. Exocrine cancer was the most common histology (90%). Young patients were significantly more likely to have an endocrine cancer (23% vs. 7%, p<0.001). For all tumor histologies, there was no difference between young and old patients regarding stage, grade, or likelihood curative intent surgery; however, young patients were more likely to receive chemotherapy (59% vs. 40%, p=0.008) and radiation therapy (27% vs. 15%, p=0.03). There was a trend toward improved overall survival in young patients (23.9 months vs. 13.8 months, p=0.06). When only exocrine pancreatic cancers were considered, there was no difference between young and old patients regarding stage, grade, location, or likelihood of undergoing surgical treatment. In this group, young patients were again more likely to receive chemotherapy (65% vs. 40%, p=0.002) and radiation therapy (35% vs. 16%, p=0.003). There was no difference in overall survival between young and old patients with exocrine pancreatic cancer. Conclusions: A considerable number of patients with pancreatic cancer are ≤ 50 years old. Exocrine cancers are the most common pancreatic neoplasm regardless of age; however endocrine tumors are more common in young patients. Despite more frequent use of adjuvant treatment in exocrine pancreatic cancer patients ≤ 50 years old, there is no improvement in overall survival. Significant improvements in pancreatic cancer survival are not dependent on aggressive use of adjuvant therapies, but await the development of new treatment strategies. No significant financial relationships to disclose.

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Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Cancers ◽

10.3390/cancers13071612 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1612

Author(s):

Julie Earl ◽

Emma Barreto ◽

María E. Castillo ◽

Raquel Fuentes ◽

Mercedes Rodríguez-Garrote ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Somatic Mutation ◽

Disease Status ◽

Clinical Analysis ◽

Cytotoxic Agents ◽

Disease Stage ◽

Ductal Adenocarcinoma ◽

Familial Pancreatic Cancer ◽

Circulating Free Dna

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.

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Long non-coding RNA PART1 predicts a poor prognosis and promotes the malignant progression of pancreatic cancer by sponging miR-122

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02232-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xibao Hu ◽

Lei Zhang ◽

Jingjing Tian ◽

Junhong Ma

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Overall Survival ◽

Clinical Stage ◽

Malignant Progression ◽

Luciferase Reporter ◽

Poor Overall Survival ◽

Pancreatic Cancer Cells ◽

Non Coding Rna ◽

Long Non Coding Rna

Abstract Background and objectives Long non-coding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was previously shown to exert an oncogenic role in several human cancers. However, whether PART1 is associated with the malignant progression of pancreatic cancer remains unclear. In the current study, we aimed to identify the role and potential mechanism of PART1 in pancreatic cancer. Methods qRT-PCR was applied to detect PART1 expression in 45 cases of pancreatic cancer patients. The chi-square test was performed to assess the association between PART1 expression and clinicopathologic features, and Kaplan-Meier method was applied to evaluate overall survival. In vitro CCK-8, transwell invasion, and flow cytometry assays were applied to detect the effects of PART1 on cell proliferation, invasion, and apoptosis, respectively. Luciferase reporter and RNA immunoprecipitation assays were used to identify the regulatory mechanism between PART1 and miR-122. Results PART1 expression was upregulated in pancreatic cancer tissues and cell lines. High PART1 expression was closely correlated with tumor size, T classification, clinical stage, and vascular invasion, and predicted a poor overall survival. PART1 knockdown significantly suppressed cell proliferation and invasion abilities of pancreatic cancer but promoted cell apoptosis. PART1 was found to serve as a molecular sponge of miR-122, and miR-122 inhibition partially reversed the inhibitory phenotypes of PART1 knockdown on pancreatic cancer cells. Conclusions PART1 promotes the malignant progression of pancreatic cancer by sponging miR-122. The PART1/miR-122 axis might be a promising target for anticancer therapy in patients with pancreatic cancer.

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Induction Chemotherapy for Primarily Unresectable Locally Advanced Pancreatic Adenocarcinoma—Who Will Benefit from a Secondary Resection?

Medicina ◽

10.3390/medicina57010077 ◽

2021 ◽

Vol 57 (1) ◽

pp. 77

Author(s):

Nathalie Rosumeck ◽

Lea Timmermann ◽

Fritz Klein ◽

Marcus Bahra ◽

Sebastian Stintzig ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Neoadjuvant Therapy ◽

Induction Therapy ◽

Locally Advanced ◽

Eastern Cooperative Oncology Group ◽

Advanced Pancreatic Cancer ◽

Comprehensive Cancer Center ◽

Secondary Resection ◽

Number Of Patients

Background and Objectives: An increasing number of patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with an intensive neoadjuvant therapy to obtain a secondary curative resection. Only a certain number of patients benefit from this intention. The aim of this investigation was to identify prognostic factors which may predict a benefit for secondary resection. Materials and Methods: Survival time and clinicopathological data of pts with pancreatic cancer were prospective and consecutively collected in our Comprehensive Cancer Center Database. For this investigation, we screened for pts with primarily unresectable pancreatic cancer who underwent a secondary resection after receiving induction therapy in the time between March 2017 and May 2019. Results: 40 pts had a sufficient database to carry out a reliable analysis. The carbohydrate-antigen 19-9 (CA 19-9) level of the pts treated with induction therapy decreased by 44.7% from 4358.3 U/mL to 138.5 U/mL (p = 0.001). The local cancer extension was significantly reduced (p < 0.001), and the Eastern Cooperative Oncology Group (ECOG) performance status was lowered (p = 0.03). The median overall survival (mOS) was 20 months (95% CI: 17.2–22.9). Pts who showed a normal CA 19-9 level (<37 U/mL) at diagnosis and after neoadjuvant therapy or had a Body Mass Index (BMI) below 25 kg/m2 after chemotherapy had a significant prolonged overall survival (29 vs. 19 months, p = 0.02; 26 vs. 18 months, p = 0.04; 15 vs. 24 months, p = 0.01). Pts who still presented elevated CA 19-9 levels >400 U/mL after induction therapy did not profit from a secondary resection (24 vs. 7 months, p < 0.001). Nodal negativity as well as the performance of an adjuvant therapy lead to better mOS (25 vs. 15 months, p = 0.003; 10 vs. 25 months, p < 0.001). Conclusion: The pts in our investigation had different benefits from the multimodal treatment. We identified the CA 19-9 level at time of diagnosis and after neoadjuvant therapy as well as the preoperative BMI as predictive factors for overall survival. Furthermore, diagnostics of presurgical nodal status should gain more importance as nodal negativity is associated with better outcome.

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