scholarly journals The GALNT14 Genotype Predicts Postoperative Outcome of Pancreatic Ductal Adenocarcinoma

2019 ◽  
Vol 8 (12) ◽  
pp. 2225 ◽  
Author(s):  
Chun-Cheng Chiang ◽  
Chau-Ting Yeh ◽  
Tsann-Long Hwang ◽  
Yu-De Chu ◽  
Siew-Na Lim ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Surgical Resection ◽  
Prognostic Marker ◽  
Postoperative Outcome ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Clinicopathological Parameters ◽  
Negative Resection Margin ◽  
Response To Chemotherapy ◽  
Significant Difference

Pancreatic ductal adenocarcinoma (PDA) is notorious for its poor prognosis. The current mainstay of treatment for PDA is surgical resection followed by adjuvant chemotherapy. However, it is difficult to predict the post-operative outcome because of the lack of reliable markers. The single-nucleotide polymorphism (SNP) of N-acetylgalactosaminyltransferase14 (GALNT14) has been proven to predict the progression-free survival (PFS), overall survival (OS) and response to chemotherapy in various types of gastrointestinal (GI) cancers. However, its role in PDA has not been studied. This study aims to investigate whether the GALNT14 SNP genotype can be a prognostic marker for PDA. A cohort of one hundred and three PDA patients having received surgical resection were retrospectively enrolled. GALNT14 genotypes and the clinicopathological parameters were correlated with postoperative prognosis. The genotype analysis revealed that 19.4%, 60.2% and 20.4% of patients had the GALNT14 “TT”, “TG” and “GG” genotypes, respectively. The patients with the “GG” genotype had a mean OS time of 37.1 months (95% confidence interval [CI]: 18.2–56.1) and those with the “non-GG” genotype had a mean OS time of 16.1 months (95% CI: 13.1–19.2). Kaplan–Meier analysis showed that the “GG” genotype had a significantly better OS compared to the “non-GG” genotype (p = 0.005). However, there was no significant difference between the “GG” and “non-GG” genotypes in PFS (p = 0.172). The baseline characteristics between patients with the “GG” and “non-GG” genotypes were compared, and no significant difference was found. Univariate followed by multivariate Cox proportional hazard models demonstrated the GALNT14 “GG” genotype, negative resection margin, and locoregional disease as independent predictors for favorable OS (p = 0.003, p = 0.037, p = 0.021, respectively). Sensitivity analysis was performed in each subgroup to examine the relationship of GALNT14 with different clinicopathological variables and no heterogeneity was found. The GALNT14 “GG” genotype is associated with favorable survival outcome, especially OS, in patients with resected PDA and could serve as a prognostic marker.

scholarly journals Homologous Recombination Deficiency in Patients With Pancreatic Ductal Adenocarcinoma and Response to Chemotherapy

2018 ◽  
pp. 1-11 ◽  
Author(s):  
Safi Shahda ◽  
Kirsten M. Timms ◽  
Ashley A. Ibrahim ◽  
Julia E. Reid ◽  
Harvey M. Cramer ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Needle Aspiration ◽  
Response To Therapy ◽  
Ductal Adenocarcinoma ◽  
Response To Chemotherapy ◽  
Formalin Fixed Paraffin Embedded ◽  
Mutation Data

Purpose Mutations or copy number abnormalities of genes involved in homologous recombination (HR) occur in pancreatic ductal adenocarcinoma (PDAC). DNA-based measures of HR deficiency (HRD) have been developed and may help identify tumors with better response to DNA-damaging agents. This study aimed to describe the HR pathway mutations and HRD status and determine their association with treatment response and outcome in patients with PDAC. Patients and Methods We performed a retrospective analysis of tumor samples from patients treated at Indiana University for locally advanced or metastatic PDAC. Patients were included if they received gemcitabine plus nanoparticle albumin-bound paclitaxel (control) or fluorouracil, oxaliplatin, leucovorin, and irinotecan (FOLFIRINOX) and had adequate follow-up to assess survival and response to therapy. Tumor analysis generated a three-biomarker HRD score and mutation data for 44 genes. Results Ninety-one samples met inclusion criteria, and 78 samples (formalin-fixed paraffin-embedded, n = 15; fine-needle aspiration, n = 63) generated mutation data. HRD analysis was successful for 57 samples (HRD score: median, 18; range, 5 to 61); the primary cause of failure was low tumor cellularity. Six BRCA1/ 2 mutations were detected, four with HRD scores in the top decile ( P = .011). There was no statistically significant correlation between HRD score and radiographic response (odds ratio per interquartile range, 1.40; P = .32 adjusted for treatment) in either treatment group. In patients treated with FOLFIRINOX, HRD score dichotomized at the median was not associated with progression-free survival (median, 5.3 v 9.4 months for low v high HRD score, respectively; P = .083) or overall survival (median, 11.9 v 10.7 months for low v high HRD score, respectively; P = .76). Conclusion Mutations in DNA repair genes occur in PDAC, and HRD scores can be generated in the majority of patients. The HRD score was not significantly associated with higher response rate or prolonged survival in patients treated with FOLFIRINOX.

scholarly journals The efficacy of current-used risk factors for metastasis and the effectiveness of additional surgical resection in pT1b esophageal squamous cell carcinoma after endoscopic resection: A multi-institutional retrospective study in China

2021 ◽  
Author(s):  
Xuemin Xue ◽  
Qi Sun ◽  
Dongxian Jiang ◽  
Xinran Wang ◽  
Yong Liu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Surgical Resection ◽  
Risk Group ◽  
Progression Free Survival ◽  
Low Risk ◽  
Clinicopathological Parameters ◽  
High Morbidity ◽  
Distant Organ Metastasis ◽  
Significant Difference ◽  
Distant Organ

Abstract Purpose ER-treated patients with pT1b ESCC were strongly recommended to receive additional treatments, mainly radical surgical resection (SR). In view of high morbidity and mortality of additional SR treatment, this recommendation remained open to debate. Herein, our research aimed to access the efficacy of current risk predictors for metastasis based on the histological findings in ER specimens, and the effectiveness of additional SR. Methods We conducted a retrospective study of ER-treated pT1b ESCC patients with (n = 42) and without (n = 124) additional SR from 2007 to 2018 in China. Lymph node metastasis & distant organ metastasis (LNM&DOM) reflecting the overall metastasis risk of ESCC after ER treatment were used. The relationships between clinicopathological parameters and metastasis were assessed. And Overall survival(OS) and progression-free survival (PFS) were also analyzed. Results Patients with submucosal invasion depth (SMI) ≥ 200µm didn't demonstrate significant difference in LNM&DOM and survival, as compared with those with SMI < 200µm.In ER alone group, patients with vertical margin(VM) (+) showed worse PFS than those with VM(-) (p = 0.008).More strikingly, for patients in low-risk group who had LVI(-) and VM(-), ER + SR didn't significantly prolong their PFS(p = 0.120) but significantly shorter their OS (p < 0.010) as compared with ER alone treatment. Conclusions SMI ≥ 200µm isn’t a sensitive and predictive indicator for both LNM&DOM and survival for patients with ER treatment. More strikingly, additional SR is not an optimal therapeutic selection for ER-treated pT1b ESCC in low-risk group who had LVI(-) and VM(-).

ESPAC-3(v2): A multicenter, international, open-label, randomized, controlled phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. LBA4505-LBA4505 ◽  
Author(s):  
J. Neoptolemos ◽  
M. Büchler ◽  
D. D. Stocken ◽  
P. Ghaneh ◽  
D. Smith ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Bolus Injection ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Open Label ◽  
Treatment Groups ◽  
Significant Difference

LBA4505 Background: Adjuvant 5-FU/FA (ESPAC-1 trial) and GEM (CONKO-001 trial) provide improved survival for patients with resected pancreatic cancer compared to no chemotherapy. The aim of the ESPAC-3 (v2) trial was to compare 5FU/FA vs GEM to identify if either adjuvant chemotherapy was associated with a significantly better survival. Methods: Patients with an R0/R1 resection for pancreatic ductal adenocarcinoma were randomized (stratified for resection margin status and country) <8 weeks of surgery to receive either 5FU/FA (FA, 20 mg/m2, iv bolus injection followed by 5-FU, 425 mg/m2, iv bolus injection given 1–5d every 28 days) or GEM (1,000mg/m2 iv infusion 1d, 8d and 15d every 4 weeks) for 6 months. The primary outcome measure was overall survival; the secondary measures were toxicity, progression free survival and quality of life. 1,030 patients were needed to detect a 10% difference in 2-year survival rates with 90% power. Results: 1,088 patients from 16 countries were randomized from July 2000 to Jan 2007 (5FU/FA = 551, GEM = 537). Median (range) age was 63 (31–85) years; 598 (55%) were men. Median tumor size was 30 (20–350) mm; 384 (35%) were R1 resections; 777 (72%) were node positive; and 263 (25%) were poorly differentiated tumors. Final analysis was carried out on an intention to treat basis with a minimum of 2 years follow-up after 753 (69%) patients had died. Median (IQR) follow-up of 335 alive patients was 34.2 (27.1–43.4) months, equal across treatment groups. Median survival from resection of patients treated with 5FU/FA was 23.0 (95% CI: 21.1, 25.0) months and for patients treated with GEM this was 23.6 (95%CI: 21.4, 26.4) months. Log-rank analysis revealed no statistically significant difference in survival estimates between the treatment groups (c2LR=0.7, p=0.39, HRGEM=0.94 (95%CI: 0.81, 1.08)). There was no significant difference in the effect of treatment across subgroups according to R status (test of heterogeneity c21=0.3, p=0.56). Conclusions: This is the largest adjuvant trial ever conducted for pancreatic ductal adenocarcinoma and showed no significant difference in survival between adjuvant 5FU/FA and adjuvant GEM. [Table: see text]

scholarly journals BRCA 1/2 Germline Mutation Predicts the Treatment Response of FOLFIRINOX with Pancreatic Ductal Adenocarcinoma in Korean Patients

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 236
Author(s):  
Ji Hoon Park ◽  
Jung Hyun Jo ◽  
Sung Ill Jang ◽  
Moon Jae Chung ◽  
Jeong Youp Park ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Treatment Response ◽  
Response Rate ◽  
Brca Mutation ◽  
Progression Free Survival ◽  
Germline Mutations ◽  
Ductal Adenocarcinoma ◽  
Korean Patients ◽  
Significant Difference ◽  
Brca 1

We evaluated the proportion of BRCA 1/2 germline mutations in Korean patients with sporadic pancreatic ductal adenocarcinoma (PDAC) and its effect on the chemotherapeutic response of FOLFIRINOX. This retrospective study included patients who were treated at two tertiary hospitals between 2012 and 2020, were pathologically confirmed to have PDAC, and had undergone targeted next-generation sequencing-based germline genetic testing. Sixty-six patients were included in the study (24 men; median age 57.5 years). In the germline test, BRCA 1/2 pathogenic mutations were found in nine patients (9/66, 13%, BRCA 1, n = 3; BRCA 2, n = 5; and BRCA 1/2, n = 1). There was no significant difference in the baseline characteristics according to BRCA mutation positivity. Among patients who underwent FOLFIRINOX chemotherapy, patients with a BRCA 1/2 mutation showed a higher overall response rate than those without a BRCA 1/2 mutation (71.4% vs. 13.9%, p = 0.004). Patients with a germline BRCA 1/2 mutation showed longer progression-free survival than those without a BRCA 1/2 mutation, without a significant time difference (18 months vs. 10 months, p = 0.297). Patients with a BRCA 1/2 mutation in the germline blood test had a higher response rate to FOLFIRINOX chemotherapy in PDAC. The high proportion of BRCA 1/2 germline mutations and response rate supports the need for germline testing in order to predict better treatment response.

Prognostic Significance of Plasma Fibrinogen/Serum Albumin Ratio in the Postoperative Outcome of Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 40 (12) ◽  
pp. 7017-7023
Author(s):  
KOICHI TOMITA ◽  
SHIGETO OCHIAI ◽  
TAKAHIRO GUNJI ◽  
KOSUKE HIKITA ◽  
TOSHIMICHI KOBAYASHI ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Significance ◽  
Postoperative Outcome ◽  
Plasma Fibrinogen ◽  
Ductal Adenocarcinoma ◽  
Albumin Ratio

scholarly journals Hypoxia-inducible proto-oncogene Pim-1 is a prognostic marker in pancreatic ductal adenocarcinoma

2008 ◽  
Vol 7 (9) ◽  
pp. 1352-1359 ◽  
Author(s):  
Carolin Reiser-Erkan ◽  
Mert Erkan ◽  
Zheng Pan ◽  
Sandor Bekasi ◽  
Nathalia A. Giese ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Marker ◽  
Ductal Adenocarcinoma

scholarly journals Preoperative Score to Stratify Recurrence Risk After Curative Resection of Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Yu Jiang ◽  
SIYI Zou ◽  
Weishen Wang ◽  
Haoda Chen ◽  
Qian Zhan ◽  
...  
Keyword(s):  
High Risk ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Score ◽  
Multidisciplinary Treatment ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Ductal Adenocarcinoma ◽  
Final Model ◽  
Significant Difference ◽  
Risk Patients

Abstract Background: Oncological survival after operation of resectable pancreatic ductal adenocarcinoma (R-PDAC) is variable depending on various factors. Preoperative risk stratification could guide decision-making in multidisciplinary treatment concepts. We develop and validate a prognostic score for disease-free survival (DFS) in R-PDAC to solve this issue.Methods: 421 R-PDAC patients between January 2012 and December 2015 were enrolled. Performance of the final model was evaluated with respect to discrimination, calibration and clinical usefulness. A prognostic score based on the final model was developed, and external validated in 290 patients.Results: On multivariable analysis, age, tumor size, carbohydrate antigen (CA)19-9, CA125, lymphocyte-monocyte ratio, and systemic-immune-inflammation index were independently associated with DFS. Final model had acceptable calibration, discrimination and internal validity. The prognostic score could delineate low- and high-risk groups with median DFS of 19.6 and 10.1 months (P<0.0001). Tumors in high-risk group exhibited more aggressive pathobiological behaviors. Additionally, at 1-year follow-up, the restricted mean survival time was longer with adjuvant chemotherapy than those without in low-risk patients. However, no significant difference was detected in high-risk patients.Discussion: The prognostic score could accurately predict DFS preoperatively in R-PDAC patients and provide reference for risk-adapted strategies formulation for R-PDAC management in the future.

scholarly journals Complete Radiologic Response of Metastatic Pancreatic Ductal Adenocarcinoma to Microwave Ablation Combined with Second-Line Palliative Chemotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Hakon Blomstrand ◽  
Karin Adolfsson ◽  
Per Sandström ◽  
Bergthor Björnsson
Keyword(s):  
Adjuvant Chemotherapy ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Palliative Chemotherapy ◽  
Lung Metastases ◽  
Performance Status ◽  
Progression Free Survival ◽  
Disease Recurrence ◽  
Ductal Adenocarcinoma ◽  
Second Line ◽  
First Line

Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis, especially for the majority of patients diagnosed with metastatic disease. The primary option for palliative treatment is chemotherapy, and responses beyond first-line treatment are rare and typically short. Here, we report a case of a 63-year-old woman with PDAC in the head of the pancreas who was initially successfully treated by pancreaticoduodenectomy followed by adjuvant chemotherapy with gemcitabine. However, disease recurrence with liver and para-aortic lymph node metastases was detected only two months after the completion of adjuvant chemotherapy. First-line palliative chemotherapy with gemcitabine-nab/paclitaxel was commenced. The results were discouraging, with disease progression (liver and lung metastases) detected at the first evaluation; the progression-free survival was just two months (64 days). Surprisingly, the response to second-line palliative chemotherapy with 5-fluorouracil-oxaliplatin was excellent; in combination with the ablation of a liver metastasis, this treatment regimen resulted in a complete radiological response and an 11-month treatment-free interval with a sustained good performance status.

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