Large-scale analysis for treatment strategy according to genetic alterations of KRAS and DPC4 (SMAD4) genes in pancreatic ductal adenocarcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 361-361
Author(s):  
Sang Hyun Shin ◽  
Song Cheol Kim ◽  
Ki Byung Song ◽  
Jae Hoon Lee ◽  
Dae Wook Hwang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Local Control ◽  
Systemic Therapy ◽  
Large Scale ◽  
Univariate Analysis ◽  
Genetic Alterations ◽  
Ductal Adenocarcinoma ◽  
Control Group ◽  
Ras Gene ◽  
Recurrence Patterns

361 Background: To investigate correlation of genetic alterations of pancreatic ductal adenocarcinoma (PDAC) with patients’ survival, recurrence patterns, and treatment for recurrent disease. Methods: We reviewed genetic alterations of major 4 genes (K-ras, DPC4, p53, and c-erbB-2) in 699 patients who underwent surgical resection, and correlated with clinical outcomes. Results: Median survival of all patients was 21.7 months, and 5-year survival rate was 20.4%. Alterational rates of each gene were as follows: K-ras, 48.3%; DPC4, 68.1%; p53, 40.8%; c-erbB-2, 14.0%. Mutation of K-ras and inactivation of DPC4 genes were associated with shorter patients’ survival in univariate analysis. In multivariate analysis, mutation of K-ras gene was independently correlated with patients’ survival (especially, GAT and TGT subtypes). Inactivated DPC4 gene had no independent correlation with overall survival, but it was strongly associated with distant metastasis following pancreatectomy. Survival after recurrence (SAR) was evaluated in subdivided groups according to DPC4 gene function (intact or loss)/recurrence patterns (locoregional or distant)/treatment options (local control or systemic therapy). In these 8 groups, patients in intact/locoregional/local control group showed the longest survival (24.2 months of median SAR), and intact/locoregional/systemic therapy and loss/distant/systemic therapy groups were associated with much shorter survival (9.5 and 9.2 months of median SAR, respectively). Conclusions: Assessment of genetic features of PDAC may assist in deciding targeted surveillance or treatment for primary as well as recurrent PDAC, and further studies for therapeutic strategies according to genetic analyses should be devised.

Predicting Surgical Margins in Patients With Borderline Resectable and Locally Advanced Pancreatic Cancer Undergoing Resection

2021 ◽  
pp. 000313482110111
Author(s):  
Weizheng Ren ◽  
Dimitrios Xourafas ◽  
Stanley W. Ashley ◽  
Thomas E. Clancy
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Resection Margins ◽  
Borderline Resectable ◽  
Stepwise Selection ◽  
R1 Resection ◽  
Positive Resection Margins

Background Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. Methods Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women’s Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis ( P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. Results A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). Conclusions Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.

Tumor cell-free DNA copy number instability compared to CA19-9 as an early predictor of response to systemic therapy in pancreatic ductal adenocarcinoma (PDAC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14524-e14524
Author(s):  
Madappa N. Kundranda ◽  
Alexander Koenig ◽  
Julia Beck ◽  
Kirsten Bornemann-Kolatzki ◽  
Jessica Coats ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Real Time ◽  
Systemic Therapy ◽  
Copy Number ◽  
Ductal Adenocarcinoma ◽  
Malignant Neoplasms ◽  
Cell Free Dna ◽  
Free Dna ◽  
Time Assessment

e14524 Background: Humoral tumor markers are used clinically for real-time assessment of therapeutic efficacy. In pancreatic ductal adenocarcinoma (PDAC) the predominant marker is CA19-9, which is not expressed by 10 to 30% of patients depending on race. We compared plasma cell-free DNA (cfDNA) copy number based assay with changes in serum CA19-9 levels and radiological responses to predict responses to systemic therapy. Methods: In a laboratory blinded, prospective multicenter pilot study, 40 non-resectable PDAC patients, treated with (m)FOLFIRINOX, CAPIRI, or gemcitabine +/- nab-paclitaxel) are currently enrolled. CA19-9 was determined in the local center’s laboratory. Tumor cfDNA was measured with a copy-number instability (CNI) scoring assay, determined by next generation sequencing in a centralized laboratory. The CNI score assesses the amount of cfDNA with somatic macro-alterations originating from malignant neoplasms. The difference of the values before commencing therapy (baseline) and prior to cycle 2 (either rising or falling) was calculated as a predictor of standardized radiological evaluation of chemotherapeutic efficacy. Results: 37 patients (3 drop-outs) had data for baseline and cycle 2, of which CA19-9 was elevated and evaluable in 29 patients. The direction from baseline to cycle 2 of CA19-9 and CNI scores were in agreement in 18/29 patients. 9 of 11 cases with discordant CNI score and CA19-9 had treatment response data, and CNI correlated with 7/9 (78%); in contrast 7/9 had rising CA19-9, when response was stable disease or better (22% concordance). In the 27 patients with available imaging, CNI predicted better (n = 18) than CA19-9 (n = 10) (p = 0.03 Fisher’s exact). Conclusions: This comparative study on cfDNA versus CA19-9 suggest that cfDNA CNI quantitation is a potentially more reliable blood based marker for early real-time assessment of efficacy in systemic PDAC therapy than CA19-9, compared to standard of care imaging. The better prediction after the first cycle might be due to the very short in vivo half-life of cfDNA ( < 1hr) compared to about one week for CA19-9. These results justify a larger prospective validation trial.

scholarly journals Local Control and Survival after Induction Chemotherapy and Ablative Radiation Versus Resection for Pancreatic Ductal Adenocarcinoma with Vascular Involvement

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Joshua S. Jolissaint ◽  
Marsha Reyngold ◽  
Jared Bassmann ◽  
Kenneth P. Seier ◽  
Mithat Gönen ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Induction Chemotherapy ◽  
Local Control ◽  
Ductal Adenocarcinoma ◽  
Vascular Involvement

scholarly journals Transcriptomic Profiling Identifies DCBLD2 as a Diagnostic and Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Zengyu Feng ◽  
Kexian Li ◽  
Yulian Wu ◽  
Chenghong Peng
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Functional Enrichment ◽  
Ductal Adenocarcinoma ◽  
Survival Curves ◽  
Cox Regression Analysis ◽  
Calibration Curves

Background: Accumulating evidence shows that the elevated expression of DCBLD2 (discoidin, CUB and LCCL domain-containing protein 2) is associated with unfavorable prognosis of various cancers. However, the correlation of DCBLD2 expression value with the diagnosis and prognosis of pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated. Methods: Univariate Cox regression analysis was used to screen robust survival-related genes. Expression pattern of selected genes was investigated in PDAC tissues and normal tissues from multiple cohorts. Kaplan–Meier (K–M) survival curves, ROC curves and calibration curves were employed to assess prognostic performance. The relationship between DCBLD2 expression and immune cell infiltrates was conducted by CIBERSORT software. Biological processes and KEGG pathway enrichment analyses were adopted to clarify the potential function of DCBLD2 in PDAC. Results: Univariate analysis, K–M survival curves and calibration curves indicated that DCBLD2 was a robust prognostic factor for PDAC with cross-cohort compatibility. Upregulation of DCBLD2 was observed in dissected PDAC tissues as well as extracellular vesicles from both plasma and serum samples of PDAC patients. Both DCBLD2 expression in tissue and extracellular vesicles had significant diagnostic value. Besides, DCBLD2 expression was correlated with infiltrating level of CD8+ T cells and macrophage M2 cells. Functional enrichment revealed that DCBLD2 might be involved in cell motility, angiogenesis, and cancer-associated pathways. Conclusion: Our study systematically analyzed the potential diagnostic, prognostic and therapeutic value of DCBLD2 in PDAC. All the findings indicated that DCBLD2 might play a considerably oncogenic role in PDAC with diagnostic, prognostic and therapeutic potential. These preliminary results of bioinformatics analyses need to be further validated in more prospective studies.

scholarly journals Serum biomarker CD163 predicts overall survival in patients with pancreatic ductal adenocarcinoma

2019 ◽  
Author(s):  
Qinglin Fei ◽  
Yu Pan ◽  
Xingxing Yu ◽  
Tianhong Teng ◽  
Ronggui Lin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Diagnostic Accuracy ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Benign Tumor ◽  
Univariate Analysis ◽  
Ductal Adenocarcinoma ◽  
Ca 125 ◽  
Operating Characteristics ◽  
Lymphocyte To Monocyte Ratio ◽  
Scd163 Level

Abstract Background The serum soluble CD163 (sCD163) is elevated in patients with infection disease and several types of cancer. However, the prognostic value of serum sCD163 in pancreatic ductal adenocarcinoma (PDAC) has not yet been investigated. Methods Serum level of sCD163 was measured by using the peripheral blood of 54 patients with PDAC, 20 patients with benign tumor of pancreas, and 30 healthy volunteers (healthy controls). The association between serum sCD163 level and overall survival was analyzed. Receiver operating characteristics (ROCs) curves were generated, and areas under the curve (AUC) were compared to evaluate the diagnostic accuracy, including CA 19-9, CEA, CA 125, CA 153, serum sCD163 level and combination of sCD163 and CA19-9. Results Serum sCD163 level of patients with PDAC was significant higher than patients with benign tumor (p = 0.002) and health controls (p < 0.001). Using ROCs curves, we found that the AUC values of serum sCD163 were higher than those of CA 125 and CA 153, but lower than those of CA 19-9 and CEA. The combination of sCD163 and CA19-9 had higher diagnostic accuracy than CA19-9 or sCD163 alone. In addition, the prognosis of PDAC patients with sCD163 ≥ median was worse than sCD163 < median by using univariate analysis (p = 0.027). Further, multivariate analysis showed that higher level of serum sCD163 was still associated with poorer overall survival (p = 0.030). Serum sCD163 was not associated with tumoral CD163 expression, whereas negatively correlated with lymphocyte to monocyte ratio (r = -0.428, p = 0.001). Conclusion The serum sCD163 has the potential as a new promising parameter to predict the prognosis in PDAC patients.

scholarly journals Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis

2020 ◽  
Vol 9 (7) ◽  
pp. 2132
Author(s):  
Bathiya Ratnayake ◽  
Alina Y. Savastyuk ◽  
Manu Nayar ◽  
Colin H. Wilson ◽  
John A. Windsor ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Neoadjuvant Therapy ◽  
Recurrence Rate ◽  
Locoregional Recurrence ◽  
Ductal Adenocarcinoma ◽  
Resectable Pancreatic Cancer ◽  
Recurrence Rates ◽  
Recurrence Patterns ◽  
Patterns Of Recurrence

Background: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. Methods: The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. Results: 26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52–0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs. 27% OR 0.39 (CI 0.22–0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44–0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34–0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts (p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05–0.32), p = 0.015). Conclusion: NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease.

Outcomes of stereotactic ablative radiotherapy for extra-cranial oligo-metastatic renal cell cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 599-599
Author(s):  
Yuanyuan Zhang ◽  
Jonathan Schoenhals ◽  
Alana Christie ◽  
Chiachien Wang ◽  
Osama Mohamad ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Cell Cancer ◽  
Local Control ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Univariate Analysis ◽  
Cell Cancer ◽  
Stereotactic Ablative Radiotherapy ◽  
Curative Intent ◽  
Free Survival

599 Background: Stereotactic ablative radiotherapy (SAbR) is a standard of care for treating renal cell cancer (RCC) cranial metastasis. We describe the effect of SAbR on oligometastatic extra-cranial RCC disease course. Methods: We retrospectively reviewed 49 patients with oligometastatic RCC with 68 extra-cranial lesions. Patients were treated with SAbR with a curative intent from 2007 to 2017. We analyzed local control, systemic therapy free survival (mPFS), and overall survival. Results: With a median follow-up of 28 months (IQR: 16.0-40.3), the 1-year and 2-year overall survival after SAbR was 93.4% (95% CI: 81.0-97.8), and 83% (95% CI: 67.4-91.5) respectively. The median overall survival was not reached. The median time to systemic therapy was 13.4 months from the first SAbR(95% CI: 8.8-27.6). Median times from the first SabR course to second and third line systemic therapy (or death) were 31.8 months and 45 months, respectively. Patients in the favorable risk group by the Heng’s criteria (HR = 8.67, p = 0.04), with nometastatic disease at diagnosis (HR = 10.38, p < 0.01) and with clear cell histology (HR = 6.15, p < 0.01) exhibited better survival, as shown by univariate analysis. Patients with no metastatic disease at diagnosis (HR = 2.56, p = 0.02) and only one metastasis treated with SAbR (HR = 2.36, p = 0.03) also exhibited better systemic therapy-free survival. SAbR had an excellent local control rate of 94% at 2 years with no reported grade 3 or higher toxicity. Conclusions: SAbR is an effective and safe treatment for oligometastatic RCC, offering excellent local control with minimal toxicity. SAbR delayed the start of systemic therapy for this RCC cohort, offering quality of life benefits for patients without adversely affecting the progression on subsequent lines of systemic therapy. These findings call for prospective verification.

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