scholarly journals Comparative Recurrence Analysis of Pancreatic Adenocarcinoma after Resection

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Chaobin He ◽  
Zhiyuan Cai ◽  
Yu Zhang ◽  
Xiaojun Lin
Keyword(s):  
Local Recurrence ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Head Group ◽  
Curative Surgery ◽  
Free Survival ◽  
Stage System ◽  
Independent Risk Factors ◽  
Different Characteristics ◽  
Recurrent Patterns

Purpose. The relation between tumor sites of pancreatic ductal adenocarcinoma (PDAC) and recurrence was not fully investigated before. We aimed to describe the differences of recurrent patterns in PDAC of head and body/tail after curative surgery. Methods. The recurrent patterns of PDAC were compared and the associations with clinical characteristics were analyzed in these patients. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed and validated. Predictive systems were constructed and measured by the area under the AUC curve and concordance index (C-index). Results. A total of 302 PDAC patients were included in this study, including 247 patients with PDAC of head and another 55 patients with PDAC of body/tail. Patients who developed tumor recurrence within 24 months after resection had significantly shorter OS in both groups. Liver metastasis occupied most of the tumor progressions and diminished while local recurrence increased gradually over time. The variation trends were similar for patients in both groups while these changes were more pronounced for patients in the head group. Local recurrence and liver-only metastasis seemed to indicate a better OS. Furthermore, predictive systems for OS and PFS prediction based on independent risk factors were established and showed significant higher values of AUC and C-indexes compared with the TNM stage system. Conclusions. Different characteristics of progressions for PDAC of head and body/tail suggested biological heterogeneity. The exploration of these variations helps to provide personalized management of recurrence in PDAC.

Clinical Outcomes and Safety of Patients Treated with NAb-Paclitaxel Plus Gemcitabine in Metastatic Pancreatic Cancer: The NAPA Study

2020 ◽  
Vol 20 (11) ◽  
pp. 887-895 ◽  
Author(s):  
Martina Catalano ◽  
Giandomenico Roviello ◽  
Raffaele Conca ◽  
Alberto D’Angelo ◽  
Valeria Emma Palmieri ◽  
...  
Keyword(s):  
Performance Status ◽  
Real Life ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Hematological Toxicity ◽  
Free Survival ◽  
Grade 3 ◽  
Ecog Ps ◽  
Prognostic And Predictive Markers

Background: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice. Methods: From January 2015 to December 2018, patients with metastatic PDAC receiving firstline treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed. Results: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95% CI; 9-13) and the median progression-free survival (PFS) was 6 months (95% CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients, respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 hematological toxicity frequency was 22.61% for neutropenia, 5.22% for anemia, and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 non-hematological events were reported. Dose reduction was necessary in 51.3% of the patients. Conclusions: Our results confirm the efficacy and safety of a first-line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.

Hyaluronan heterogeneity in pancreatic ductal adenocarcinoma, primary tumors, and sites of metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16231-e16231
Author(s):  
Veronica Placencio-Hickok ◽  
Marie Lauzon ◽  
Natalie Moshayedi ◽  
Michelle Guan ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastasis ◽  
Regression Model ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
High Status ◽  
Free Survival ◽  
Pdac Tissue ◽  
Treatment Naïve

e16231 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with an estimated five-year survival rate of 10%. The dense desmoplastic stroma in PDAC contributes to its aggressive nature and treatment resistance. Among the components comprising the stroma, hyaluronan (HA) has been demonstrated to play a critical role in tumor progression and survival. Previous preliminary studies have suggested differences in HA expression in primary and metastatic foci in PDAC. However, the effects of treatment and location of HA expression as well as the role of CD44, a known receptor for HA, on HA as a biomarker signature remain unknown. Thus, we investigated the potential of HA as a biomarker in primary PDAC and metastases. Methods: PDAC tissue from primary (n = 43) and metastatic (n = 66) sites were obtained from Cedars-Sinai Medical Center along with associated clinical data. Tissue slides were stained with H&E, HA using a histochemical assay, and CD44 by immunohistochemistry. HA staining was scored according to the proportion of stromal staining at an intensity greater than the background stroma. HA status was defined as ≥ 50% staining being HA high and < 50% as being HA low. CD44 staining was recorded as an H-score (percentage of tumor cells staining multiplied by intensity of staining on a scale from 0 to 3). Associations between HA levels and the requested variables were examined with t-test, Wilcoxon rank-sum test, Chi-squared test, Fisher’s exact test, or Cox regression model where appropriate. Kaplan-Meier curves were created to assess progression free survival and overall survival. Analyses were performed using SAS 9.4 with two-sided tests and a significance level of 0.05. Results: HA score was significantly higher in primary PDAC tissue compared to sites of metastases (p = 0.0148). Within the metastases, HA score was significantly higher in liver metastasis compared to other sites of metastasis (p = 0.0478). In the liver metastasis tissue, HA score trended lower in patients with previously treated tissue compared to treatment naïve tissue (p = 0.0622). In the treatment naive liver metastasis cohort, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status (p = 0.0032 and p = 0.0478, respectively). Using HA score and CD44 in a Cox regression model demonstrated that for every one unit increase in HA score, the risk for recurrence/progression increased by 4.4% at any fixed point in time, adjusting for CD44 score (p = 0.0049). Conclusions: HA score is variable between primary PDAC, PDAC metastatic to the liver, and PDAC metastatic to other sites. Within liver metastases, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status. HA levels can serve as a potential biomarker to guide pancreatic cancer treatments and trial design for agents targeting the stroma.

scholarly journals Prognostic significance of advanced lung cancer inflammation index (ALI) in multiple myeloma patients – a retrospective study

2021 ◽  
Author(s):  
Junxia Huang ◽  
Juanjuan Hu ◽  
Yan Gao ◽  
Fanjun Meng ◽  
Tianlan Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Advanced Lung Cancer ◽  
Free Survival ◽  
Factors Influencing ◽  
Independent Risk Factors ◽  
Cancer Inflammation

Abstract Background: Advanced lung cancer inflammation index (ALI) is known to predict the overall survival of patients having some solid tumors or B-cell lymphoma. The study investigates the predictive value of ALI in multiple myeloma (MM) patients and the correlation between ALI and prognosis.Methods: A database of 269 MM consecutive patients who underwent chemotherapy between December 2011 and June 2019 in the Affiliated Hospital of Qingdao University was reviewed. ALI cut-off value calculated before the initial chemotherapy and post 4 courses treatment were identified according to the receiver operating characteristic (ROC) curve, and its association with clinical characteristics, treatment response, overall survival (OS), and progression-free survival (PFS) were assessed.Results: Patients in the low ALI group (n=147) had higher risk of β2 microglobulin elevation, more advanced ISS (International Classification System stage), and TP53 gene mutation, with significantly lower median overall survival (OS; 36.29 vs. 57.92 months, P = 0.010) and progression-free survival (PFS; 30.94 vs. 35.67 months, P = 0.013). Independent risk factors influencing the OS of MM patients were ALI (P = 0.007), extramedullary infiltration (P = 0.001), TP53 (P = 0.020), Plt (P = 0.005), and bone destruction (P = 0.024). ALI (P = 0.005), extramedullary infiltration (P = 0.004), TP53 (P = <0.001), Plt (P = 0.017), and complex chromosome karyotype (P = 0.010) were independent risk factors influencing the PFS of MM patients.Conclusions: ALI is a potential independent risk factor predicting the prognosis of newly diagnosed MM patients.

scholarly journals Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 64 (4) ◽  
pp. 726-734 ◽  
Author(s):  
Min Kyeong Kim ◽  
Sang Myung Woo ◽  
Boram Park ◽  
Kyong-Ah Yoon ◽  
Yun-Hee Kim ◽  
...  
Keyword(s):  
Kras Mutation ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Multiplex Detection ◽  
Kras Mutations ◽  
Cell Free Dna ◽  
Free Survival ◽  
Free Dna ◽  
Fractional Abundance ◽  
Prognostic Implications

Abstract BACKGROUND Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. METHODS A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad). RESULTS KRAS mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20–3.63] and KRAS fraction (HR, 1.73; 95% CI, 1.02–2.95) were significant factors for progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05–3.67) also had prognostic implications for overall survival. Subgroup analyses showed that KRAS mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC (P = 0.016). Moreover, when combined with the cancer biomarker CA19-9, the KRAS mutation concentration in cfDNA showed additive benefits for the prediction of overall survival. CONCLUSIONS This study demonstrates that multiplex detection of KRAS mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC.

Imatinib mesylate therapy in advanced gastrointestinal stromal tumors—A Regional cancer centre experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 19505-19505
Author(s):  
K. M. Patel ◽  
P. M. Shah ◽  
S. N. Shukla ◽  
B. J. Parikh ◽  
A. S. Anand ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Imatinib Mesylate ◽  
Metastatic Disease ◽  
Gastrointestinal Stromal Tumors ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stromal Tumors ◽  
Post Surgery

19505 Background: The treatment of gastrointestinal stromal tumors has been revolutionised by the advent of Imatinib, a specific tyrosine kinase inhibitor. Post operative local and metastatic recurrences of this tumor have been effectively managed by Imatinib. Here we present our experience of Imatinib in recurrent locally advanced/metastatic gastrointestinal stromal tumors (GIST). Methods: From Nov 2001 to Sep 2005, 33 patients with metastatic and / or locally advanced inoperable CD-117 positive GIST were offered imatinib mesylate therapy at 400 mg/day p.o. A total of 21 patients were evaluable for tumor response. Follow up period ranged from 4 months to 38 months with median follow up period being 18 months. Median age is 58 yrs, M:F ratio is 6:4. ECOG performance status was 0–1 in 70% (23 patients) and 2 in 30% (10 patients). 70% patients had post surgery recurrence. 2 patients (6%) had received adjuvant chemotherapy prior to recurrence. 30% (10 patients) had local recurrence, 40% (13 patients) had metastatic disease while 30% (10 patients) had local recurrence as well as metastatic disease. Results: Response evaluation was done by RECIST criteria. 15% (5 patient) showed CR while PR rates were 30% (10 patients). The overall major response (CR+PR) was 45%. The overall progression free survival was as high as 80%. All the patients who had a progression free survival also had a significant improvement in quality of life. Conclusions: Imatinib mesylate therapy shows significant survival benefits in locally advanced inoperable/metatstatic gastrointestinal stromal tumors. It will be a very long time before PET scan for evaluation and follow up becomes feasible in developing country setting. No significant financial relationships to disclose.

Preliminary results from a phase II study of infusional 5-FU, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer (mCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3579-3579 ◽  
Author(s):  
S. Kopetz ◽  
J. L. Abbruzzese ◽  
C. Eng ◽  
R. B. Adinin ◽  
J. Morris ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Curative Surgery ◽  
Free Survival ◽  
Preliminary Results ◽  
Grade 3 ◽  
First Line Treatment

3579 Background: Irinotecan (I) plus bolus 5-FU (F) and leucovorin (L) comprise the IFL regimen, a very active treatment in mCRC when combined with bevacizumab (B). The response rate (RR) for IFL-B given as first-line treatment is 45%, with a median progression-free survival (PFS) of 10.6 months and a median survival of 20.3 months. The IFL regimen is now considered inferior to infusional 5-FU regimens, such as FOLFIRI, which have less toxicity and improved efficacy. Methods: We designed a 43 patient (pt), single-arm phase II trial of FOLFIRI-B with B (5mg/kg), I (180mg/m2), bolus of F (400mg/m2) and L (400mg/m2) followed by a 46-hour infusion of F (2400mg/m2), with a primary endpoint of progression-free survival (PFS). Chemotherapy naïve mCRC patients (pts) with adequate organ function and performance status 0–2 received B alone on Day minus 14, starting FOLFIRI + B on Day 1. DCE-MRI and laboratory correlates were completed before and after B alone and cycle 1. Once cycle is equivalent to two weeks. Results: 21 pts, median age 59 y/o (range 26–75), M:F = 15:6, 4 with prior F in adjuvant setting, have been enrolled to date. 20 pts are evaluable for response. One pt is too early. A total of 215 cycles have been administered (median 11). Median PFS has not been reached after a median follow-up of 8 months. By intent-to-treat analysis, there were 14 PRs (70%), and 5 (25%) pts with stable disease observed (including 1 unconfirmed PR). PRs were observed from 9 to 35 weeks after the first cycle (median: 18 weeks). 9 pts remain on treatment (1–12 months); 12 pts are off study (3 for progressive disease, 1 withdrew, 4 sent for curative surgery, 2 for toxicity, 2 sent for surgery unrelated to cancer). Toxicity included 10 cases of grade 3 neutropenia, including 1 febrile neutropenia, 4 venous thrombi, and 6 cases of hypertension requiring medication change. One pt included in the analysis developed peritonitis, considered a possible microperforation, after B alone and never received FOLFIRI. No ≥ grade 3 diarrhea was observed. Analysis of correlative studies will be presented at a later date. Conclusion: Our preliminary results indicate that FOLFIRI-B is well tolerated and an excellent choice as a first-line treatment for mCRC. [Table: see text]

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 Salvage Radiotherapy for Macroscopic Local Recurrence Following Radical Prostatectomy

2021 ◽  
Vol 11 ◽  
Author(s):  
Hind Zaine ◽  
Benjamin Vandendorpe ◽  
Benoit Bataille ◽  
Thomas Lacornerie ◽  
Jennifer Wallet ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Local Recurrence ◽  
Hormone Therapy ◽  
Progression Free Survival ◽  
Salvage Radiotherapy ◽  
Metastatic Progression ◽  
Free Survival ◽  
Prostate Bed ◽  
Concomitant Boost ◽  
Biochemical Progression

IntroductionSalvage radiotherapy is the only curative treatment for biochemical progression after radical prostatectomy. Macroscopic recurrence may be found in the prostatic bed. The purpose of our study is to evaluate the effectiveness of salvage radiotherapy of the prostate bed with a boost to the area of the macroscopic recurrence.Material and MethodsFrom January 2005 to January 2020, 89 patients with macroscopic recurrence in the prostatectomy bed were treated with salvage radiotherapy +/- hormone therapy. The average PSA level prior to radiotherapy was 1.1 ng/mL (SD: 1.6). At the time of biochemical progression, 96% of the patients had a MRI that revealed the macroscopic recurrence, and 58% had an additional choline PET scan. 67.4% of the patients got a boost to the macroscopic nodule, while 32.5% of the patients only underwent radiotherapy of the prostate bed without a boost. The median total dose of radiotherapy was 70 Gy (Min.: 60 – Max.: 74). The most commonly-used regimen was radiotherapy of the prostatectomy bed with a concomitant boost. 48% of the patients were concomitantly treated with hormone therapy.ResultsAfter a median follow-up of 53.7 months, 77 patients were alive and 12 had died, of which 4 following metastatic progression. The 5-year and 8-year survival rates (CI95%) are, respectively, 90.2% (78.9-95.6%) and 69.8% (46.4-84.4%). The 5-year biochemical progression-free survival rate (CI95%) is 50.8% (36.7-63.3). Metastatic recurrence occurred in 11.2% of the patients. We did not find any statistically significant impact from the various known prognostic factors for biochemical progression-free survival. No toxicity with a grade of &gt; or = to 3 was found.ConclusionsOur series is one of the largest published to date. Salvage radiotherapy has its place in the management of patients with biochemical progression with local recurrence in the prostate bed, with an acceptable toxicity profile. The interest of the boost is to be evaluated in prospective trials.

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