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Background: Liquid biopsy analysis for EGFR detection in cell-free DNA (cfDNA) from NSCLC patients has become routine. The aim of this study was to explore its applicability in clinical practice. Methods: We collected data of EGFR-mutated... more
Background: Liquid biopsy analysis for EGFR detection in cell-free DNA (cfDNA) from NSCLC patients has become routine. The aim of this study was to explore its applicability in clinical practice. Methods: We collected data of EGFR-mutated NSCLC patients with liquid biopsy analysis. Data included test timing, concomitant tissue re-biopsy, therapy change, histology, stage, smoking habits, gender and age. All analyses were performed via a real-time PCR method to analyze EGFR mutations at exons 18, 19, 20 and 21. Variant allele frequency was performed for patients with available sequential EGFR mutation analysis in cfDNA. Overall survival was analyzed through the Kaplan–Meier method. We designed flow charts to show the real-life application of liquid biopsy. Results: We found that liquid biopsy is used in treatment-naïve patients as an alternative to EGFR detection in tumor tissue, and in patients with positive or negative EGFR from tumor biopsy. The majority of liquid biopsy analyses w...
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e15055 Background: In literature three studies have described KRAS status in SCAC: they analyzed 139 patients, only 1, 4% were mutated. In this study we analyzed BRAF and PIK3CA status. The evaluation of these two genes is important for... more
e15055 Background: In literature three studies have described KRAS status in SCAC: they analyzed 139 patients, only 1, 4% were mutated. In this study we analyzed BRAF and PIK3CA status. The evaluation of these two genes is important for predicting the response to anti-EGFR drugs. There is one study that values the positivity of HPV in SCAC. This study with few patients shows that the positivity of HPV16 is predictive for improvement of progression free survival (PFS). Methods: 79 patients were treated for anal cancer at the Oncology center of Forlì, Ravenna and Faenza in the last ten years. Up to now we analyzed 29 patients (9 with relapse of disease). DNA was extracted from paraffin-embedded sections and KRAS, BRAF and PIK3CA gene status were assessed by Pyrosequencing methodology, using 3 different kits: anti-EGFR MoAb response (KRAS status), anti-EGFR MoAb response (BRAF status), and anti- EGFR MoAb response (PIK3CA status) (Diatech, Jesi, Ancona, Italy). Reactions were run on a ...
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The identification of the mutations that drive lung cancer have furnished new targets for the treatment of non-small cell lung cancer (NSCLC) and led to the development of targeted therapies such as tyrosine kinase inhibitors that are... more
The identification of the mutations that drive lung cancer have furnished new targets for the treatment of non-small cell lung cancer (NSCLC) and led to the development of targeted therapies such as tyrosine kinase inhibitors that are used to combat the molecular changes promoting cancer progression. Furthermore, biomarkers identified from gene analysis can be used to detect early lung cancer, determine patient prognosis, and monitor response to therapy. In the present study we analyzed the molecular profile of seventy-three Tunisian patients with lung adenocarcinoma (LAD). Mutational analyses for EGFR and KRAS were performed using direct sequencing, immunohistochemistry or MassARRAY. Anaplastic lymphoma kinase (ALK) rearrangement was evaluated by immunohistochemistry using the D5F3 clone, and p53 expression was also assessed. The median age of patients at diagnosis was 61 years (range 23–82 years). Using different methodologies, EGFR mutations were found in 5.47% of patients and on...
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3603 Background: KRAS mutations negatively affect outcome after cetuximab (CTX) in metastatic colorectal cancer (mCRC). As only 20% of KRAS wild-type (WT) patients respond it is possible that other mutations, constitutively activating the... more
3603 Background: KRAS mutations negatively affect outcome after cetuximab (CTX) in metastatic colorectal cancer (mCRC). As only 20% of KRAS wild-type (WT) patients respond it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding WT. We retrospectively correlated KRAS, BRAF and PI3K mutational status with the clinical outcome of 64 mCRC patients treated with CTX plus chemotherapy. METHODS DNA was extracted from 5 mM paraffin-embedded sections containing at least 50% of tumoral cells, derived from primary or metastatic lesions. Exon 2 of KRAS and exon 15 of BRAF were amplified by PCR and analysed by direct sequencing. PIK3CA status was analysed by Pyrosequencing. A two-sided Fisher's exact test was used to evaluate the association between mutations and objective response (OR). Progression-free survival (PFS) was estimated by Kaplan-Meier method and curves were compared by log-rank test. Hazard ratios (HR) were estimated according to Cox multiple regression model. RESULTS Patient characteristics were as follows: Male/Female = 35/29; primary site: rectum/colon =13/51. KRAS, BRAF and PI3K mutations were present in 28.1%, 21.3% and 15.1% of CRC lesions, respectively. KRAS WT/MUT was associated with OR 28.3/22.2% (p=0.75), median PFS 5.1 (95% CI 3.3-6.2)/3.1 months (95%CI 2.3-5.5), p=0.85. BRAF WT/MUT was associated with OR 33.3/7.7% (p=0.08), PFS 5.1 (95% CI 2.9-6.5)/3.4 months (95%CI 1.4-5.1), p<0.01. PI3K WT/MUT was associated with OR 31.1/12.5% (p=0.41), PFS 5.3(95% CI 3.6-6.5)/2.2 months (95% CI 1.1-3.3), p<0.01. PFS (95% CI) was increasingly worse for patients with tumors harboring none, 1, or ≥ 2 molecular alteration(s): 5.5 (2.7-8.7), 3.5 (2.3-5.5), 2.1 months (1.0-3.9), respectively, p<0.01. Moreover, the multivariate analysis of PFS indicated BRAF and PI3K as potential independent predictors of clinical benefit: HR (95% CI) 2.74 (1.37-5.45), p<0.01 and 3.57 (1.45-8.80), p<0.01, respectively. CONCLUSIONS Our results seem to confirm that comprehensive molecular dissection of the EGFR signaling pathways should be considered to better select mCRC patients for CTX based therapies.
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Purpose: To analyze the impact of TP53 mutations on response to first-line tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non-small cell lung cancer (NSCLC).Experimental Design: 136 EGFR-mutated NSCLC patients receiving... more
Purpose: To analyze the impact of TP53 mutations on response to first-line tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non-small cell lung cancer (NSCLC).Experimental Design: 136 EGFR-mutated NSCLC patients receiving first-line TKIs were analyzed. TP53 mutations were evaluated in 123 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).Results:TP53 mutations were observed in 37 (30.1%), 10 (27.0%), 6 (16.2%), 9 (24.3%), and 12 (32.4%) patients in exons 5, 6, 7, and 8, respectively. DCR was 70% in TP53-mutated patients compared with 88% in TP53-wild type (wt) patients [relative risk, RR, of disease progression: 3.17 (95% CI, 1.21-8.48), P = 0.019]. In particular, a 42% DCR was observed in patients with TP53 exon 8 mutation versus 87% in exon 8 wt patients [RR of disease progression 9.6 (2.71-36.63), P < 0.001]. Shorter median PFS and OS were observed in patients with TP53 ex...
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Epidermal growth factor receptor (EGFR) is usually expressed in squamous cell anal carcinoma (SCAC) and anti-EGFR agents could represent a valid treatment strategy, also considering that KRAS and BRAF mutations are rare events in this... more
Epidermal growth factor receptor (EGFR) is usually expressed in squamous cell anal carcinoma (SCAC) and anti-EGFR agents could represent a valid treatment strategy, also considering that KRAS and BRAF mutations are rare events in this type of cancer. However, no data are available on NRAS status in SCAC. In this study we analyzed NRAS status (exons 2–4) by Pyrosequencing in a case series of 50 SCAC patients previously characterized in our laboratory for KRAS, BRAF, PIK3CA mutations and HPV and HIV infections. We found no mutation in NRAS gene. These results confirm that since the principal anti-EGFR resistance mechanisms are almost absent in SCAC, anti-EGFR agents should be considered for the treatment of this type of cancer.
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In non-small cell lung cancer (NSCLC) patients, somatic EGFR and K-ras mutations predict therapeutic effectiveness and resistance, respectively, to EGFR tyrosine kinase inhibitors (TKIs). Transesophageal ultrasound-guided fine needle... more
In non-small cell lung cancer (NSCLC) patients, somatic EGFR and K-ras mutations predict therapeutic effectiveness and resistance, respectively, to EGFR tyrosine kinase inhibitors (TKIs). Transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) is a validated technique for diagnosis and staging of NSCLC. In the present study, we compared the feasibility and reliability of EGFR and K-ras gene mutation analysis in fixed and fresh mediastinal lymph nodes and extra-lymph nodal samples obtained by EUS-FNA in patients suspicious for NSCLC. Thirty-six patients were enrolled into the study. For each patient, DNA was extracted from both fresh samples and fixed cytological smears. Exons 18-21 of EGFR and exon 2 of K-ras were amplified by PCR and mutation status was determined by direct sequencing and pyrosequencing. All cases were eligible for analysis. NSCLC was diagnosed in 32 patients (25 adenocarcinomas and 7 squamous cell carcinomas) and 4 patients were free of malignancy. Of t...
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Background KRAS mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC) patients. As only 20% of KRAS wild type (WT) patients respond to cetuximab it is possible that other mutations,... more
Background KRAS mutations negatively affect outcome after treatment with cetuximab in metastatic colorectal cancer (mCRC) patients. As only 20% of KRAS wild type (WT) patients respond to cetuximab it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding KRAS WT patients. We retrospectively analyzed objective tumor response rate, (ORR) progression-free (PFS) and overall survival (OS) with respect to the mutational status of KRAS, BRAF, PIK3CA and PTEN expression in mCRC patients treated with a cetuximab-based regimen. Methods 67 mCRC patients were enrolled onto the study. DNA was extracted from paraffin-embedded sections derived from primary or metastatic lesions. Exon 2 of KRAS and exon 15 of BRAF were analyzed by direct sequencing, PIK3CA was evaluated by pyrosequencing and PTEN expression by immunohistochemistry. Results BRAF and PIK3CA mutations were independently associated with worse PFS (p = 0.006 and p = 0.028, respect...
Research Interests: Immunohistochemistry, Medicine, Colorectal cancer, Multivariate Analysis, Humans, and 15 moreInternal Medicine, Female, Male, Monoclonal Antibodies, Aged, Middle Aged, Adult, BRAF, KRAS, Cetuximab, Exon, Metastatic Colorectal Cancer, Colorectal Neoplasms, Disease Free Survival, and Medical and Health Sciences
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There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular... more
There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter "Italian Trial in Advanced Colorectal Cancer (ITACa)", randomized to receive first-line chemotherapy (CT) or CT plus bevacizumab (CT + B). RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX2), ephrin type-B receptor 4 (EPHB4), hypoxia-inducible factor 1-alpha (HIF-1α), lactate dehydrogenase (LDH), and high-sensitivity C reactive protein (hs-CRP); and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-infl...
Research Interests: Genetics, Inorganic Chemistry, Molecular Biology, Catalysis, Biomarkers, and 15 moreMedicine, Colorectal cancer, Humans, Internal Medicine, Mutation, Female, Male, Molecular sciences, Bevacizumab, Colon, Metastatic Colorectal Cancer, Colorectal Neoplasms, Combined Modality Therapy, Neoplasm grading, and Inflammation Mediators
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... 978-88-95608-14-3 ISSN 1974-9791 DOI: 10.3303/CET1023053 Improvement of the dispersion of odour through conveying Sonia Zanetti1, Andrea ... produces compost; the treatment is conducted in closed sheds and the odorous gases are... more
... 978-88-95608-14-3 ISSN 1974-9791 DOI: 10.3303/CET1023053 Improvement of the dispersion of odour through conveying Sonia Zanetti1, Andrea ... produces compost; the treatment is conducted in closed sheds and the odorous gases are conveyed to biofilters (Mc Nevin, 2000 ...
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With regards to the new odour guidelines that are going to be issued by the district of Lombardia, in Italy, a general approach for the determination of the maximum odour emission scenario of new installations is presented. First, the... more
With regards to the new odour guidelines that are going to be issued by the district of Lombardia, in Italy, a general approach for the determination of the maximum odour emission scenario of new installations is presented. First, the main items to be considered ...
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ABSTRACT Different approaches can be adopted in order to validate the results of odour dispersion modelling. This paper describes the approach adopted for odour dispersion modelling considering the specific case of a MSW landfill located... more
ABSTRACT Different approaches can be adopted in order to validate the results of odour dispersion modelling. This paper describes the approach adopted for odour dispersion modelling considering the specific case of a MSW landfill located in Northern Italy. This work represents the first step of a more extended research project between Ecole des Mines d’Alès and Politecnico di Milano, which will study different approaches to evaluate the exposure to odours and odorous compounds.
ABSTRACT Different types of models can be used to simulate the odour dispersion into the atmosphere. This work aims to compare two dispersion models that are widely used for regulatory purposes (Dresser and Huizer, 2011): the... more
ABSTRACT Different types of models can be used to simulate the odour dispersion into the atmosphere. This work aims to compare two dispersion models that are widely used for regulatory purposes (Dresser and Huizer, 2011): the steady-state, U. S. Environmental Protection Agency (EPA) model AERMOD, and the non-steady-state puff model CALPUFF. The comparison focuses on how meteorological conditions (i.e., stable vs. instable conditions) and source type (i.e., point vs. area source) affect the modelling results, thereby allowing to analyse the differences based on the characteristic dispersion equations of the two above mentioned models.