KOC (K homology domain containing protein overexpressed in cancer) overexpression and progression-free survival after curative intent resection of pancreatic ductal adenocarcinoma.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 48-48
Author(s):  
Benny Johnson ◽  
Maged F. Khalil ◽  
Fan Lin ◽  
Shaobo Zhu ◽  
Lester Kirchner
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Distant Metastasis ◽  
Rna Binding ◽  
Progression Free Survival ◽  
The United States ◽  
Ductal Adenocarcinoma ◽  
Patient Specific ◽  
Rank Test ◽  
Curative Intent ◽  
Free Survival

48 Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality in the United States. Unfortunately, effective screening and early detection mechanisms are currently unavailable, thereby 80% of patients present with distant metastasis. Of the subset of patients eligible for curative intent surgery, the 5-year survival rate is only 20%. Negative surgical margins, tumor size, stage, and node negative disease are traditional prognostic indicators. However, these can be limited in their ability to predict patient specific prognosis. KOC is an oncofetal RNA-binding protein involved in RNA stabilization and cell growth during embryogenesis. Previous studies have revealed that KOC mRNA is inappropriately overexpressed in pancreatic cancer and that increased expression correlates with tumor stage. In this study, we attempt to identify whether KOC expression in patients who undergo curative intent surgery correlates with progression free survival. Methods: Tissue microarrays prepared from formalin-fixed, paraffin-embedded specimens of patients with PDAC who underwent curative intent surgery were assessed by immunohistochemistry. Results: A total of 35 patients were included. Comparisons between groups on progression free survival are estimated using the Kaplan-Meier method and the log-rank test. KOC was overexpressed in 23.6% of tumors. It was found that there were zero patients with a high KOC expression and no distant metastasis. Patients with a high KOC expression were more than 3 times more likely to progress compared to those with a low KOC expression (HR=3.54, 95% CI: 1.34, 9.36, p=0.011). Conclusions: KOC is a useful prognostic biomarker for predicting those patients with PDAC who have a high risk for early progression and distant metastasis. Identifying patients with high KOC expression upon initial diagnosis can serve as a way to risk stratify patients to aggressive treatment regimens upfront and early exposure to clinical trials.

Investigating the prognostic value of a panel of biomarkers after curative intent resection of pancreatic ductal adenocarcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 211-211
Author(s):  
Benny Johnson ◽  
Maged F. Khalil ◽  
Joseph Blansfield ◽  
Fan Lin ◽  
Shaobo Zhu ◽  
...  
Keyword(s):  
Distant Metastasis ◽  
Expression Patterns ◽  
Progression Free Survival ◽  
The United States ◽  
Ductal Adenocarcinoma ◽  
Patient Specific ◽  
Rank Test ◽  
Ki 67 ◽  
Curative Intent ◽  
Free Survival

211 Background: Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality in the United States. 80% of tumors are discovered with distant metastasis upon presentation. Of patients eligible for curative intent surgery, the 5-year survival rate is only 20%. Identification of a panel of biomarkers correlated with patient specific prognosis upon diagnosis can serve as a way to individualize treatment options. Methods: A retrospective cohort study analyzing pathology of patients who underwent curative intent surgery at our institution from 1998-2011 to identify whether the expression patterns of six biomarkers:S100P, Maspin, KOC, CEA, p53, and Ki-67 can be predicative of patient specific prognosis. Tissue microarrays of specimens were assessed by immunohistochemistry. Results: A total of 62 patients are included. Comparisons between groups on overall survival (OS) and progression free survival (PFS) are estimated using the Kaplan-Meier method and the log-rank test. Each biomarker was represented as low and high expression by categorizing the expression score at >4, based on intensity and extent of cells stained. 40 deaths occurred in the sample. Distant metastasis and differentiation (well/moderate vs. poor) were borderline related to OS (p=0.0120, p=0.0086). Interestingly, patients with a poor differentiation were less likely to die due to any cause (HR=0.41, 95% CI: 0.21, 0.82). 29 patients progressed in their disease. High/low KOC expression were significantly related to progression free survival (p=0.0556). Incorporating previously reported data on KOC, patients with a high KOC expression were more than 2 times more likely to progress compared to those with a low KOC expression (HR=2.04, 95% CI: 0.97, 4.29). Conclusions: In our study S100P, Maspin, CEA, p53 and Ki-67 expression patterns were not statistically significant in identifying PFS or OS in PDAC patients. However, our data is suggestive of KOC being a useful prognostic biomarker for identifying those patients with PDAC who have a high risk for early progression and distant metastasis. Larger studies are needed to determine whether KOC can be a therapeutic target in the treatment of pancreatic cancer.

scholarly journals Efficacy and safety of second-line nab-paclitaxel plus gemcitabine after progression on FOLFIRINOX for unresectable or metastatic pancreatic ductal adenocarcinoma: multicenter retrospective analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592092342 ◽  
Author(s):  
Heejung Chae ◽  
Hyehyun Jeong ◽  
Jaekyung Cheon ◽  
Hong Jae Chon ◽  
Hyewon Ryu ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Retrospective Analysis ◽  
Treatment Option ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Grade 3

Background: FOLFIRINOX (fluorouracil, folinic acid, irinotecan plus oxaliplatin) is an effective standard first-line treatment option for advanced pancreatic ductal adenocarcinoma (PDAC). There is no clear consensus on the second-line treatment following progression on FOLFIRINOX. In this multicenter retrospective analysis, we evaluated the efficacy and tolerability of second-line nab-P/Gem (nab-paclitaxel and gemcitabine) after progression on FOLFIRNOX in PDAC. Methods: Patients with unresectable or metastatic PDAC who received nab-P/Gem after progression on FOLFIRINOX between February 2016 and February 2019 were identified from five referral cancer centers in South Korea. Baseline characteristics, treatment history, survival outcomes, and toxicity profile were obtained retrospectively from medical records. Results: A total of 102 patients treated with second-line nab-P/Gem for advanced PDAC after progression on FOLFIRINOX were included. At the time of nab-P/Gem, the median age was 60 years, with males comprising 49.0%, and most (75.5%) had metastatic disease. Patients received a median of three cycles (range 1–12) of nab-P/Gem. The median overall survival (OS) and progression-free survival (PFS) from the start of second-line nab-P/Gem therapy were 9.8 (95% CI, 8.9–10.6) and 4.6 months (3.7–5.5), respectively. A partial response was achieved in 8.5%, and the disease control rate was 73.6%. From the start of first-line FOLFIRIOX, the OS1+2 and PFS1+2 were 20.9 (15.7–26.1) and 13.9 (10.8–17.0) months, respectively, with a 2-year survival rate of 45.1%. There was no treatment-related mortality and grade ⩾3 toxicity was observed in 60.2%. Conclusion: Our results showed that nab-P/Gem was an effective and tolerable second-line treatment option in medically fit patients with advanced PDAC who progressed on first-line FOLFIRNOX. ClinicalTrials.gov identifier: NCT04133155

DocOx (AIO-PK0106): A phase II trial with docetaxel and oxaliplatin as a second-line systemic therapy for patients with advanced and/or metastatic adenocarcinoma of the pancreas—Final results.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 352-352 ◽  
Author(s):  
Thomas Jens Ettrich ◽  
Lukas Perkhofer ◽  
Volker Kaechele ◽  
Andreas W. Berger ◽  
Melanie Guethle ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Control ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Response ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Second Line ◽  
Free Survival ◽  
Grade 3

352 Background: Pancreatic ductal adenocarcinoma still remains a major cause of cancer related deaths in the western world. The current study was conducted to confirm the activity and feasibility of docetaxel/ oxaliplatin combination in second line treatment of advanced pancreatic ductal adenocarcinoma. Methods: Prospective single arm, non-randomized, multi-center, Simon’s two stage phase II trial using docetaxel (75 mg/m2, 60 min, d 1) and oxaliplatin (80 mg/m2, 120 min, d 2) in 21-day cycles. Duration of the trial was scheduled up two 8 cycles. Primary endpoint was tumor response according to RECIST 1.0. Secondary endpoints were progression free survival, overall survival, safety/toxicity, quality of life and clinical benefit. Results: Data represents the intention to treat analysis of 44 patients included between 2008 and 2012. The majority of patients received a gemcitabine based first-line chemotherapy (95.5%). The primary endpoint of tumor response was achieved in 15.9% (7 partial remissions, no complete remission), with a disease control rate of 48% after the first two treatment cycles. Median progression free survival was 7 weeks (CI 6-15.9 weeks) and overall survival 40 weeks (CI 20.4-56.4 weeks). No unexpected adverse events occured. The recorded AEs were mainly hematologic (neutropenia grade 3/4 63.6%, febrile neutropenia 4.6%), gastrointestinal (29.6% grade 3/4 AEs) and infectious (18.2% grade 3/4 AEs). Conclusions: In this single-arm second line trial for the treatment of advanced PDAC, the combination of docetaxel and oxaliplatin shows promising results comparable with other second line protocols such as OFF (oxaliplatin, 5-FU, leucovorin) or liposomal irinotecan (MM-398) plus 5-FU/leucovorin (NAPOLI 1-trial). Some patients seem to benefit particularly as indicated by long periods of treatment in this setting. Even after 8 cycles of treatment with DocOx, partial response was observed in 2 patients and stable disease in another 6 patients corresponding to a disease control rate of 18%. The toxicity profile was quite tolerable and comparable to other second line studies. Clinical trial information: NCT00690300.

The prognostic value of stroma desmoplasia in pancreatic ductal adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 211-211
Author(s):  
Emmanouil Fokas ◽  
Michael A Silva ◽  
Zenobia D'Costa ◽  
Robin Bockelmann ◽  
Zahir Soonawalla ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Adjuvant Chemotherapy ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Value ◽  
Smooth Muscle Actin ◽  
Progression Free Survival ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
Local Progression

211 Background: Pancreatic ductal adenocarcinoma (PDAC) often presents an abundant desmoplastic stroma. We assessed the prognostic value of stroma density and activity in patients with resectable PDAC treated with surgery and adjuvant gemcitabine-based chemotherapy. Methods: FFPE-tissue originating from the pancreatectomy of 145 patients was immunohistochemicallystained for haematoxylin-eosin and Masson’s trichrome to assess stroma density, and alpha-smooth muscle actin (αSMA) expression for activated pancreatic stellate cells. Their expression was correlated with clinicopathological characteristics as well as overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS). Results: After a mean follow-up of 20 months (range, 2-69 months), the median OS was 21 months and the 3-year OS was 35.7 %. In multivariate analysis, highly-dense stroma was an independent prognostic parameter for OS (p = 0.001), PFS (p = 0.007), LPFS (p = 0.001) and DMFS (p = 0.002), while αSMA expression lacked significance. Interestingly, highly-dense stroma retained significance for the four clinical endpoints only in early (pT1-2) but not late (pT3-4) stage tumors. Additionally, late pT-stage (pT3-4), the presence of lymph node metastases (pN+ vs pN0), perineural/neural invasion PNI and adjuvant chemotherapy also correlated with prognosis in multivariate analysis. Conclusions: In summary, stroma density represents an independent prognostic marker in PDAC patients treated with adjuvant chemotherapy. Our findings highlight the complexity of desmoplasia and indicate that highly-dense stroma is associated with better outcome. Further validation of the prognostic value of stroma as a biomarker and its role in PDAC biology is warranted and will be performed in a prospective study.

scholarly journals hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1808 ◽  
Author(s):  
Jerome Raffenne ◽  
Remy Nicolle ◽  
Francesco Puleo ◽  
Delphine Le Corre ◽  
Camille Boyez ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Predictive Value ◽  
Mrna Level ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Nucleoside Transport ◽  
Ductal Adenocarcinoma ◽  
Primary Tumors ◽  
Free Survival ◽  
Multicenter Cohort

Gemcitabine is still one of the standard chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC). Gemcitabine uptake into tumor cells is mainly through the human equilibrative nucleoside transport 1 (hENT1). It was therefore proposed as a potential predictive biomarker of gemcitabine efficacy but reports are conflicting, with an important heterogeneity in methods to assess hENT1 expression. A multicenter cohort of 471 patients with a resected PDAC was used to assess simultaneously the predictive value of the 2 best described hENT1 antibodies (10D7G2 and SP120). Three additional antibodies and the predictive value of hENT1 mRNA were also tested on 251 and 302 patients, respectively. hENT1 expression was assessed in 54 patients with matched primary tumors and metastases samples. The 10D7G2 clone was the only hENT1 antibody whose high expression was associated with a prolonged progression free survival and overall survival in patients who received adjuvant gemcitabine. hENT1 mRNA level was also predictive of gemcitabine benefit. hENT1 status was concordant in 83% of the cases with the best concordance in synchronous metastases. The 10D7G2 clone has the best predictive value of gemcitabine benefit in PDAC patients. Since it is not commercially available, hENT1 mRNA level could represent an alternative to assess hENT1 status.

scholarly journals Nanoliposomal irinotecan plus fluorouracil and folinic acid as a second-line treatment option in patients with metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Se Jun Park ◽  
Hyunho Kim ◽  
Kabsoo Shin ◽  
Tae Ho Hong ◽  
Ja Hee Suh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Nanoliposomal Irinotecan ◽  
Previously Treated

Abstract Background According to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to haematological toxicity. There has been limited information on the clinical benefits and toxicity of this regimen in real-world settings. In this study, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure. Methods We conducted a single institution, retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80 mg/m2) with 5-FU/LV every 2 weeks. Kaplan-Meier analysis was performed to obtain median progression free survival and median overall survival. The hazard ratio and 95% confidence interval (CI) were estimated using a stratified Cox regression model. A multivariate Cox proportional hazards regression model was used to identify the effects of clinical factors. Results Fifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% CI 1.8–3.7) and median overall survival was 7.0 months (95% CI 6.0–7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced grade 3 or 4 adverse events, most commonly neutropenia (58.8%). Most non-haematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1–18.4). Conclusions Nal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, following gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Nal-IRI plus 5-FU/LV following gemcitabine with nab-paclitaxel is a feasible sequential treatment option in patients with metastatic pancreatic cancer. Trial registration Retrospectively registered.

On-treatment progression-free survival analysis of ziv-aflibercept/FOLFIRI treatment within 28 days of end of treatment in metastatic colorectal cancer: Updated efficacy results from the VELOUR study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3573-3573
Author(s):  
David Ferry ◽  
Tae Won Kim ◽  
Tormod Kyrre Guren ◽  
Jayesh Desai ◽  
Luis Marcelo Villanueva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Rank Test ◽  
Free Survival

3573 Background: The phase III VELOUR study demonstrated that adding the novel antiangiogenic agent ziv-aflibercept (known as aflibercept outside the United States) to FOLFIRI in patients with metastatic colorectal cancer previously treated with oxaliplatin significantly improved overall survival, progression-free survival (PFS), and overall response rate vs placebo/FOLFIRI. We performed an additional analysis of PFS “on-treatment,” censoring events that occurred more than 28 days after last treatment dose. Methods: Patients were randomized to receive ziv-aflibercept 4 mg/kg or placebo every 2 weeks in combination with FOLFIRI. An independent review committee determined progression based on radiologic review. PFS was estimated using Kaplan-Meier analysis, with censoring of events after the last dose plus 28 days. Treatment groups were compared using a log-rank test and were stratified by Eastern Cooperative Oncology Group performance status and prior bevacizumab therapy. Hazard ratio (HR) and confidence interval (CI) were estimated using a Cox proportional hazard model. Results: On-treatment analysis showed significantly increased PFS for patients treated with ziv-aflibercept/FOLFIRI compared with placebo/FOLFIRI (Table). More patients were censored in the ziv-aflibercept arm due to adverse events. Conclusions: The on-treatment PFS analysis demonstrates a significantly improved treatment effect of the addition of ziv-aflibercept to FOLFIRI (HR=0.55) over what was observed in the primary analysis suggesting that continuing treatment with ziv-aflibercept up to disease progression provides additional benefit. Clinical trial information: NCT00561470. [Table: see text]

Neoadjuvant therapy outcomes in nonmetastatic pancreatic cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 501-501
Author(s):  
Jeanette Muniz Kovtun ◽  
Konstantin Kovtun ◽  
Koenraad Mortele ◽  
James Moser ◽  
Andrea J. Bullock
Keyword(s):  
Neoadjuvant Therapy ◽  
Clinical Stage ◽  
Multidisciplinary Treatment ◽  
Treatment Algorithm ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Vascular Involvement ◽  
Free Survival ◽  
Local Progression

501 Background: The optimal multidisciplinary treatment algorithm for pancreatic ductal adenocarcinoma (PDAC) is not well established. We studied outcomes in non-metastatic PDAC treated with chemotherapy and stereotactic body radiation therapy (SBRT) with or without pancreatic resection. Methods: Between August 2011 and July 2015, 73 patients with non-metastatic PDAC were treated with chemotherapy and SBRT with or without resection. Variables considered included: ECOG, CA 19-9, clinical stage, vascular involvement, pathologic stage and margin status. Resectability status was determined by an expert abdominal radiologist on initial staging imaging. Chemotherapy included FOLFIRINOX, FOLFOX, gemcitabine monotherapy (gem) or with nab-paclitaxel (gem/nab). SBRT was delivered as 30 Gy in 3 fractions over 5 days via CyberKnife. The Kaplan-Meier method and log-rank test were used to compare median overall survival (mOS), local progression free survival (LPFS) and metastasis free survival (MFS). Results: After a median follow-up of 19.3 months (mo) the mOS was 30.0 mo (95% CI, 19.4 to 36.5). The surgical group had longer mOS (36.5 vs 19.4 mo; P < 0.001), LPFS (29.0 vs 16.3 mo; P = 0.03) and MFS (29.0 vs 15.1 mo; P < 0.001) as compared to the nonsurgical group. FOLFIRINOX or gem/nab was associated with better mOS as compared to other chemotherapy (33.2 vs 12.8 mo; P < 0.001). There was a trend towards longer mOS in pts with initial imaging deemed less resectable (36.5 vs 30.1 vs 13.0 mo in unresectable vs borderline vs resectable; P = 0.19). In a multivariate analysis significant predictors of OS were resection, ECOG and FOLFIRINOX or gem/nab chemotherapy. Conclusions: Patients who had surgery after neoadjuvant chemotherapy and SBRT had significantly longer mOS, LPFS and MFS than those without surgery. FOLFIRINOX or gem/nab and better ECOG were also associated with improved outcomes. Worse resectablity status per imaging was associated with longer OS despite less likelihood of surgery; This may reflect more intensive neoadjuvant therapy or suggest that radiologic resectability status is a poor predictor of OS. Further investigation of factors underlying this discrepancy may have implications on neoadjuvant strategy and resectability determination.

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