LDH serum levels as a predictive factor for global outcome in pretreated colorectal cancer patients receiving regorafenib: Implications for clinical management.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 497-497 ◽  
Author(s):  
Michela Del Prete ◽  
Mario Scartozzi ◽  
Tiziana Prochilo ◽  
Luca Faloppi ◽  
Riccardo Giampieri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Roc Curve Analysis ◽  
Group A ◽  
Group B ◽  
Colorectal Cancer Patients

497 Background: Although a demonstrated clinical efficacy, a non negligible proportion of colorectal cancer patients does not seem to benefit from regorafenib and are consequently exposed to unnecessary toxicity. LDH serum levels represent an indirect marker of tumour hypoxia, neo-angiogenesis and worse prognosis in many tumour types. In colorectal cancer LDH showed a correlation with treatment outcome for patients receiving antiangiogenetic treatment, thus suggesting a possible interaction with the activity profile of these drugs. We analyzed the role of LDH serum levels in predicting clinical outcome for pre-treated metastatic colorectal cancer patients receiving regorafenib. The final aim was to individuate a potentially reliable and easy to use marker for patients stratification. Methods: 118 colorectal cancer patients treated with regorafenib were available for our analysis. For all patients, LDH values were collected within one month before the procedure and after treatment end. LDH cutoff value was determined by ROC curve analysis, patients were then divided into two groups (A and B, below and above cut-off level respectively). Patients were also classified according to the variation in LDH serum levels pre- and post-treatment (increased patients vs. decreased patients). Results: Patients in group A and B proved homogeneous for all clinical characteristics analyzed. In group A patients median progression free survival (PFS) was 3.18 months, whereas it was 1.87 months in group B patients (p = 0.0018). Median overall survival (OS) was 6.23 months and 3.28 months in group A and B respectively (p = 0.048). Significant differences were not noted among the 2 groups for response rate. All the other clinical variables analyzed failed to show any correlation with patients outcome. Conclusions: Our observations seem to suggest a role of LDH as a marker of clinical outcome in colorectal cancer patients receiving regorafenib. We can then speculate that high LDH patients may not be optimal candidates for regorafenib. After further confirmation in larger trial, these findings may be relevant for a better patients stratification and selection.

scholarly journals Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 595-595 ◽  
Author(s):  
Riccardo Giampieri ◽  
Lisa Salvatore ◽  
Michela Del Prete ◽  
Tiziana Prochilo ◽  
Marco D'Anzeo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Therapeutic Index ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Colorectal Cancer Patients ◽  
Ecog Ps

595 Background: The introduction of regorafenib for the treatment of colorectal cancer represented a sure medical achievement though at a cost of relevant toxicity. As a consequence the lack of predictive factors made the use of regorafenib in the clinical practice challenging. Previous observations suggested that polymorphisms of VEGF and its receptor (VEGFR) genes may regulate angiogenesis and lymphangiogenesis and potentially influence outcome during anti-angiogenesis treatment. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. Methods: From a multicentre experience 138 samples (tumour or blood samples) of colorectal cancer patients receiving regorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients’ progression-free survival (PFS) and overall survival (OS) were analysed. Results: Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS (respectively HR: 0.49, 95% CI: 0.33-0.81, p=0.003 and HR: 0.52, 95% CI: 0.34-0.99, p=0.04). A correlation with disease control rate (DCR) was also observed (DCR 55% vs. 26%, p=0.02). Among clinical factors only ECOG PS was independently correlated with OS (HR: 0.52, 95% CI: 0.21-0.81, p=0.009), whereas no correlation with PFS was evident. Grouping together observations from angiogenesis genotyping and ECOG PS allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. Median OS resulted progressively decreased across these groups (OS not reached, 7.8 and 3.9 months respectively in the favourable, intermediate and unfavourable group, p<0.0001). Conclusions: VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of candidates for regorafenib. This selection opportunity will ultimately improve the therapeutic index of such a treatment approach by limiting treatment to potentially responding patients and sparing unnecessary toxicity to those unlikely to benefit.

scholarly journals Prognostic clinical factors in pretreated colorectal cancer patients receiving regorafenib: Implications for clinical management.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 591-591
Author(s):  
Michela Del Prete ◽  
Riccardo Giampieri ◽  
Fotios Loupakis ◽  
Tiziana Prochilo ◽  
Lisa Salvatore ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Cancer Patients ◽  
Lymphocyte Count ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Clinical Factors ◽  
Roc Curve Analysis ◽  
Related Factors ◽  
Colorectal Cancer Patients

591 Background: Most of the patients receiving regorafenib do not seem to benefit from this treatment approach and are therefore exposed to unnecessary toxicity. Angiogenesis and inflammation-related factors may have a relevant role in modulating the activity of anti-angiogenetic drugs such as regorafenib. In our study, we investigated LDH serum levels, platelet, neutrophil, and lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR) in predicting clinical outcomes for colorectal cancer patients receiving regorafenib. The final aim was to individuate an easy to use and reliable selection tool for these patients in the clinical practice. Methods: We collected LDH serum levels, neutrophil, lymphocyte, and platelet counts within one month before the start of regorafenib in 208 pretreated metastatic colorectal cancer patients. Cut-off values were calculated by ROC curve analysis. Survival analysis was performed by Kaplan-Meier method, and multivariate analysis by Cox method. Results: At multivariate analysis: high platelet count (p=0.0439), low lymphocyte count (p=0.0013), and high NLR (p=0.0237) were related to worse overall survival (OS); high neutrophil count and high NLR (p=0.0058) were related to worse progression free survival (PFS). Among 52 (25%) patients who were negative for all risk factors, a significant correlation was found with improved OS and PFS if compared with the group of patients with at least one risk factor. In particular, median OS was respectively 15.9 vs. 3.1 months (HR: 3.81, 95% CI: 2.32-4.82, p<0.0001) whereas median PFS was 5.9 vs. 2.1 months (HR: 2.62, 95% CI: 2.06-3.86, p<0.0001). Conclusions: We can speculate that colorectal cancer patients showing high neutrophil, high platelet, low lymphocyte count or high NLR may not be optimal candidates for regorafenib treatment. After confirmation in further prospective series, these clinical factors could play a role in the treatment strategy process.

LDH serum levels as prognostic and predictive factor in advanced biliary tract cancer patients treated with first-line chemotherapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 313-313
Author(s):  
Luca Faloppi ◽  
Michela Del Prete ◽  
Mario Scartozzi ◽  
Daniele Santini ◽  
Maristella Bianconi ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Serum Levels ◽  
First Line ◽  
Tract Cancer ◽  
Group A ◽  
Group B ◽  
Line Chemotherapy

313 Background: Previous data suggested that LDH serum levels may be associated with tumour hypoxia and VEGFA and VEGFR-1 over-expression. LDH may then represent an indirect marker of activated tumour neo-angiogenesis and worse prognosis in many tumour types. In our analysis, we analyzed the role of LDH serum levels in predicting clinical outcome for biliary tract cancer patients treated with first-line cisplatin and gemcitabine chemotherapy, to individuate a potentially reliable and easy to use marker for patients stratification. Methods: 71 advanced biliary tract cancer patients treated with cisplatin and gemcitabine in first-line chemotherapy were available for our analysis. For all patients, LDH values were collected within one month before treatment beginning. We chose the laboratory cut-off (Upper Normal Rate, UNR) as LDH cut-off value (450 U/l) and then we divided the patients into two groups (A and B, below and above the UNR respectively). Survival distribution was estimated by the Kaplan-Meier method. Disease control rate (DCR) was assessed with chi-square test. A significant level of 0.05 was chosen to assess the statistical significance. Results: Patients in group A (46 patients) and B (25 patients) proved homogeneous for all clinical characteristics analyzed. Median progression free survival (PFS) was 3.97 months and 1.8 months respectively in group A (patients with LDH level below the UNR) and in group B (patients with LDH level above the UNR), p=0.0064 (HR=2.07, 95%CI: 1.07-3.99). Median overall survival (OS) was 9.24 months and 2.55 months in group A and B respectively, p<0.0001 (HR=2.93; 95%CI: 1.37-6.27). DCR was 65% in group A vs. 21% in group B (p=0.004). Conclusions: Our observations seem to suggest a prognostic role of LDH in biliary tract cancer patients. Our findings showing an improved PFS and DCR in patients with low LDH serum levels also suggest a possible predictive role in patients treated with a cisplatin and gemcitabine regimen as first-line chemotherapy. After further confirmation in larger trial, these results may be relevant for a better patients stratification and selection.

Correlation of activated AKT and MAPK expression in liver metastases with clinical outcome in colorectal cancer patients receiving irinotecan/cetuximab treatment.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 449-449
Author(s):  
Mario Scartozzi ◽  
Riccardo Giampieri ◽  
Alessandra Mandolesi ◽  
Elena Maccaroni ◽  
Michela Del Prete ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Primary Tumour ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Wild Type ◽  
Altered Expression ◽  
Phosphorylated Akt ◽  
Colorectal Cancer Patients

449 Background: An aberrant activation of the EGFR downstream signaling pathway via MAP-kinase and Akt could be responsible for resistance to anti-EGFR treatment. We tested the interaction between phosphorylated Akt and MAPK in primary colorectal tumours and corresponding metastases and clinical outcome in terms of response rate (RR), progression free survival (PFS) and overall survival (OS) to identify a group of patients more likely to benefit from EGFR-targeted treatment among those harbouring a K-RAS wild type status. Methods: Seventy-two advanced K-RAS wild type colorectal cancer patients treated with irinotecan-cetuximab were analysed. Primary tumour were available in all cases, whereas paired tumour samples from metastatic sites were available in 37 patients. Phosphorylated Akt and MAPK were analyzed by immunohistochemistry. Results: Akt resulted overexpressed in 31 primary tumours (43%) and 23 metastases (62%), whereas MAPK was over-expressed in 32 primary tumours (44%) and 20 metastases (54%). Akt altered expression in primary tumours correlated with a statistically significant worse median PFS (2.4 months vs. 6.5 months, p= 0.0006) and OS (7.8 months vs. 26.7 months, p < 0.0001), without any significant correlation with RR. No significant correlation could be found between MAPK expression in primary tumours and RR, PFS or OS. In metastases Akt expression correlated with RR (9% vs, 58%, p= 0.004), PFS (2.3 months vs.9.2 months p < 0.0001) and OS (6.1 months vs.26.7 months p < 0.0001). Analogously MAPK expression in metastases correlated with RR (10% vs, 47%, p = 0.002), PFS (2.3 months vs.8.6 months p < 0.0001) and OS (7.8 months vs.26 months p = 0.0004). At multivariate analysis Akt and MAPK status in metastases was able to independently predict PFS. Akt status in metastases independently correlated with RR as well. Conclusions: We suggest that Akt and MAPK expression in metastases may have a relevant role in determining the activity of anti-EGFR treatment strategies. Our observations seem also to indicate that for some molecular determinants of resistance the biological profile in metastases is prominent.

scholarly journals The Role of HER‐3 Expression in the Prediction of Clinical Outcome for Advanced Colorectal Cancer Patients Receiving Irinotecan and Cetuximab

2011 ◽  
Vol 16 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Mario Scartozzi ◽  
Alessandra Mandolesi ◽  
Riccardo Giampieri ◽  
Alessandro Bittoni ◽  
Chiara Pierantoni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Advanced Colorectal Cancer ◽  
Colorectal Cancer Patients

scholarly journals Adamalysines as Biomarkers and a Potential Target of Therapy in Colorectal Cancer Patients: Preliminary Results

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Katarzyna Walkiewicz ◽  
Joanna Strzelczyk ◽  
Dariusz Waniczek ◽  
Krzysztof Biernacki ◽  
Małgorzata Muc-Wierzgoń ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Distant Metastases ◽  
Serum Levels ◽  
Control Group ◽  
Colorectal Cancer Patients ◽  
And Control ◽  
The Relationship ◽  
Increased Activity

Colorectal cancer is one of the most common cancers in the world. Due to its still undetermined pathogenesis, we are searching for signaling pathways that are important in the development of colorectal cancer. In this article, we present results of study on the role of ADAM proteins in colorectal cancer. The study included 85 adult colorectal cancer patients (48 men, 37 women) and 25 patients in the control group (after diagnostic colonoscopy—without cancer). During hospitalization, a serum sample (3 cm3) was collected from the study and control group, anthropometric measurements were conducted and others clinical data were analyzed. In the serum ADAM10, 12, 17, and 28, protein concentrations were determined and, in the next step, examined the relationship between ADAMs concentrations and selected clinical parameters in both groups. The analysis showed that serum levels of ADAM10 and ADAM28 are significantly higher in patients with colorectal cancer and correlate with histopathological grading and with presence of distant metastases. Moreover, noticed the trend to correlate concentrations of adamalysines with higher BMI score. One of the functions of adamalysines is the activation of growth factors involved in cancer, including IGF and TNFα. The increased activity of adamalysines in patients may play a role in the pathogenesis of colorectal cancer. Our study highlights the prevalence of metabolic disorders in the group of patients with diagnosed CRC, and this cancer seems to be a further complication of obesity.

scholarly journals The Role of Vascular Endothelial Growth Factorin Thrombocytosis in Colorectal Cancer Patients

2018 ◽  
Vol 2 (2) ◽  
pp. 1-7
Author(s):  
Subandrate Subandrate ◽  
Dwi Indira Setyorini ◽  
Mediarty Mediarty ◽  
Irsan Saleh
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Research Subjects ◽  
Elisa Technique ◽  
Average Serum ◽  
Colorectal Cancer Patients ◽  
Endothelial Growth Factor

Backgorund: Colorectal cancer was included in a group of cancer with various complications. One complication that was often a cause of morbidity and mortality was thrombocytosis. In colorectal cancer, the incidence of thrombocytosis associated with the formation of blood vessels around the tumor or angiogenesis. Factors that played an important role in angiogenesis was vascular endothelial growth factor (VEGF). Methods: This study was an observational analytic research in colorectal cancer patients to determine the correlation levels of platelets and serum VEGF levels. A total of 33 patients with colorectal cancer at the Palembang Mohammad Hoesin Hospital be research subjects to examine the levels of platelets and levels of VEGF. The level of serum VEGF was performed using ELISA technique from SIGMA®. Results: The average level of the patient's platelets was281,090.9±105,860.8/mm3.  In this study, two patients (6.06%) have thrombocytosis.The average serum levels of VEGF research subjects were 221.2 ± 152.8 pg/mL.Correlation test of levels of serum VEGF and platelets levels showed the value of p=0.040 (p> 0.05) and r = 0468. Conclusions: Thus, it can be concluded that in this research serum VEGF levels are almost always causes an increase in platelet levels in patients with colorectal cancer.

Clinical usefulness of mtTFA expression as a predictive marker in colorectal cancer patients treated with FOLFOX

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4059-4059
Author(s):  
Y. Yoshida ◽  
J. Hasegawa ◽  
R. Nezu ◽  
Y. Kim ◽  
M. Hirota ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Physical Interaction ◽  
Primary Tumors ◽  
P53 Expression ◽  
Response To Chemotherapy ◽  
Colorectal Cancer Patients

4059 Background: We previously reported that mitochondrial transcription factor A (mtTFA; also designated Tfam) preferentially recognizes cisplatin-damaged DNA via physical interaction with p53 and is upregulated by the treatment with cisplatin and 5-FU (Yoshida et al, Cancer Res. 2003). The aim of this study was to evaluate whether expression of mtTFA predicts clinical outcome in patients with metastatic colorectal cancer treated with modified FOLFOX6 (mFOLFOX6). Methods: From January 2006 to April 2008, 59 patients who had metastatic lesions from colorectal cancer treated with mFOLFOX6 at the Osaka Rosai Hospital were included in this study. They consisted of 25 women (42.4%) and 34 men (57.6%), with a median age of 62 years (29–84). Patients were treated with oxaliplatin 85mg/m2 plus leucovorin 200mg/m2 as a 2-h infusion at day 1, followed by 5-FU bolus 400mg/m2 and 46-h continuous infusion of 2400 mg/m2. Treatment was repeated in 2-week intervals for at least 4 cycles. The expressions of mtTFA and p53 of resected primary tumors were examined by immunohistochemistry. Results: Among 59 patients, one complete response and 32 partial responses were observed (response rate, 55.9%) . The positive rates was 44.1% (26/59; CR 1, PR 7, SD/PD 18) for mtTFA and 59.3% (35/59; CR 1, PR 19, SD/PD 15) for p53, respectively. Strong expression of mtTFA was detected in 8 of 33 CR/PR (24.2%) and in 18 of 26 SD/PD (69.2%), indicating that the expression of mtTFA correlated significantly with response to chemotherapy (P<0.01). On the other hand, there was no significant correlation between response to chemotherapy and p53 expression (P=0.82). mtTFA expression was significantly associated with overall survival (P=0.036) and progression free survival (P=0.037). Multivariate analysis revealed that mtTFA expression significantly impacted on OS (Hazard ratio 2.10, P=0.036). Conclusions: Immunohistochemical study of mtTFA may be useful in prediction of the clinical outcome of metastatic colorectal cancer patients treated with FOLFOX. No significant financial relationships to disclose.

Phosphorylated Akt and MAPK expression in primary tumors and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14086-e14086
Author(s):  
Riccardo Giampieri ◽  
Mario Scartozzi ◽  
Elena Maccaroni ◽  
Alessandra Mandolesi ◽  
Simona Biagetti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Primary Tumors ◽  
Kaplan Meier ◽  
Phosphorylated Akt ◽  
Line Setting ◽  
Colorectal Cancer Patients

e14086 Background: Other than the well-known EGFR pathway activation via the Ras-Raf-MAP-kinase, a possible role of other potential biomarkers could be relevant in determining resistance to anti-EGFR treatment, such as the protein-serine/threonine kinase Akt. We tried to assess the role of Akt and MAPK expression in metastatic colorectal cancer patients and their relationship with outcome for patients receiving Irinotecan-Cetuximab. Methods: Eligible patients were metastatic colorectal cancer patients treated in 2nd or 3rd line setting with a irinotecan-cetuximab based regimen. Patients were tested for K-ras status and subsequently assessed by immunoistochemistry for pAkt and MAPK expression, both in primary tumours and metastases whenever sufficient tissue was available. The role of pAkt and MAPK expression was evaluated for K-ras wild type patients for different likelihood of response, overall survival and progression free survival. Response was evaluated by RECIST criteria. Survival analysis was performed via Kaplan-Meier method. Results: In metastases pAkt correlated with RR (9% vs. 58%, p=0.004), PFS (2.3 months vs.9.2 months p < 0.0001) and OS (6.1 months vs.26.7 months p < 0.0001) and pMAPK correlated with RR (10% vs, 47%, p = 0.002), PFS (2.3 months vs.8.6 months p < 0.0001) and OS (7.8 months vs.26 months p=0.0004). At multivariate analysis pAkt and pMAPK in metastases were able to independently predict PFS. pAkt in metastases independently correlated with RR as well. Conclusions: pAkt and pMAPK expression in metastases may modulate the activity of EGFR-targeted antibodies. We could speculate that in patients with pAkt and pMAPK metastases expression targeting these factors may be crucial.

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