RESUMO
Ischemic bowel disease is considered a high-risk factor for infection from anaerobic bacteria, as the ischemic bowel is the perfect ground for their development. Herein, we present the case of an advance stage colon cancer patient with a rare cause of gastrointestinal bleeding and bacteremia due to Clostridium paraputrificum, a rare anaerobic Gram-positive bacterium. The patient had presented with several episodes of hematochezia in the context of chronic superior mesenteric-portal vein tumor thrombosis and rupture of ectopic varices, and the bacteremia was an unexpected complication of the bowel ischemia due to a combination of arterial ischemia and venous congestion.
RESUMO
BACKGROUND/AIM: Real-world data on the EGFR mutational profile upon progression after first/second-generation EGFR-TKI treatment in patients with advanced non-small-cell lung cancer (NSCLC) and treatment strategies employed thereon are needed. PATIENTS AND METHODS: This observational study was conducted in 23 hospital-based lung cancer Centers in Greece (protocol code: D133FR00126). Ninety-six eligible patients were consecutively enrolled between July-2017 and September-2019. Re-biopsy was performed in 18 of 79 patients who tested T790M-negative in liquid biopsy after progression in the first-line (1L) setting. RESULTS: Of the study population, 21.9% tested T790M-positive, while 72.9% proceeded to 2L treatment, mainly comprising of a third-generation EGFR-TKI (48.6%), a switch to chemotherapy (30.0%), or chemo-immunotherapy (17.1%). The objective response rate (ORR) in 2L was 27.9% in T790M-negative and 50.0% in T790M-positive patients. Of evaluable patients, 67.2% experienced disease progression; median progression-free survival (PFS) was 5.7 and 10.0 months among T790M-negative and positive patients, respectively. Among T790M-negative patients, longer median PFS and post-progression survival were observed with third-generation EGFR-TKI treatment. CONCLUSION: Mutational status and treatment strategy were identified as critical determinants of clinical outcomes in the 2L-setting of EGFR-mutated NSCLC patients in real-world settings in Greece, with early diagnosis, appropriate molecular testing and high-efficacy treatments at first lines positively affecting ORR and PFS.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Receptores ErbB/uso terapêutico , Mutação , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Aim: To retrospectively characterize real-world therapeutic strategies, clinical outcomes and attrition rates with EGFR tyrosine kinase inhibitors (TKIs), before first-line osimertinib approval, in EGFR-mutated advanced/metastatic non-small-cell lung cancer patients in Greece. Results: Among 160 patients, the discontinuation rate for first-line first- or second-generation EGFR-TKIs was 85%; among these patients, 43% did not receive any second-line therapy and 9.4% died during an 18.7-month follow-up period. Median progression-free and overall survival were 12.1 and 20.9 months, respectively. Osimertinib was offered as second- and third-line treatment in 69.6 and 21.7% of patients with the T790M mutation, respectively. Brain metastases were recorded in 10.6% of patients during treatment, with median overall survival of 4.9 months. Conclusion: Given the high attrition rates and the impact of CNS progression, offering the most appropriate first-line EGFR-TKI treatment with CNS penetration is key to maximize outcomes.
Based on the results of clinical and real-world studies, EGFR tyrosine kinase inhibitors (EGFR-TKIs) are considered the first-line standard of care for people with a type of cancer, know as EGFR-mutant advanced/metastatic non-small-cell lung cancer. However, treatment patterns and outcomes after progression are less well reported and could impact the first-line EGFR-TKI therapeutic approach. This study is part of a large European analysis of real-world evidence, known as the REFLECT study, the objective of which is to learn more about the characterization of testing and treatment patterns, as well as attrition rates, in people receiving first-line treatment with first- or second-generation EGFR-TKIs. Clinical Trial Registration: NCT04031898 (ClinicalTrials.gov) or D5162R00009.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas , Compostos de Anilina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Grécia/epidemiologia , Humanos , Indóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas , Estudos RetrospectivosRESUMO
OBJECTIVES: Colorectal cancer (CRC) is the second leading cause of cancer in Europe, with 1.931.590 people newly diagnosed in 2020. The purpose of this study is the investigation of treatment options and healthcare resource metastatic CRC (mCRC) in Greece. METHODS: This study is based on the information collected in November 2020 by an expert panel comprising of 6 medical oncologists from major public and private centers around Greece. A 3-round survey was undertaken, according to Delphi method. The treatment phases studied were: pre-progression; disease progression and terminal care. Pharmaceutical costs and resource utilization data were considered from the perspective of the Greek National Services Organization (EOPYY). RESULTS: Experts agreed that the anticipated prevalence of RAS mutation in mCRC is 47% (30% RAS/BRAF WT Left, 17% RAS/BRAF WT Right); 8% BRAF while, MSI-H/dMMR are found in 5% of mCRC tumors. Based on mutational status, 74.8% of patients receive biological targeted therapies in combination with fluoropyrimidine/based combination chemotherapy, as 1st line treatment, and 25.2% combination chemotherapy alone. At 2nd line, 58.6% of patients receive biological targeted therapies in combination with chemotherapy, 25.4% immunotherapy, 11% combination chemotherapy and 5% biological targeted therapies. At 3rd line 56% of patients receive combination chemotherapy, 28% biological targeted therapies, 10% biological targeted therapies in combination with chemotherapy and 6% immunotherapy. The weighted annual cost (pharmaceuticals and resource use cost) in 1st line per mCRC patient was calculated at 28,407, in 2nd line 33,568, in 3rd line 25,550. The annual cost beyond 3rd line per patient regardless mutation was 19,501 per mCRC patient. CONCLUSIONS: mCRC is a societal challenge for healthcare systems as the treatment is more prolonged but expand patients' survival. Thus, reimbursement decisions should be based not just on the cost of the treatment, but on the magnitude of the benefit of its treatment on patients' survival and quality of life.
RESUMO
Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform cobas®EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.
RESUMO
BACKGROUND: Analysis of circulating tumor nucleic acids in plasma of Non-Small Cell Lung Cancer (NSCLC) patients is the most widespread and documented form of "liquid biopsy" and provides real-time information on the molecular profile of the tumor without an invasive tissue biopsy. METHODS: Liquid biopsy analysis was requested by the referral physician in 121 NSCLC patients at diagnosis and was performed using a sensitive Next Generation Sequencing assay. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 50 patients by both the cobas and NGS platforms. RESULTS: At least one mutation was identified in almost 49% of the cases by the NGS approach in NSCLC patients analyzed at diagnosis. In 36 cases with paired tissue available a high concordance of 86.11% was observed for clinically relevant mutations, with a Positive Predictive Value (PPV) of 88.89%. Furthermore, a concordance rate of 82% between cobas and the NGS approach for the EGFR sensitizing mutations (in exons 18, 19, 21) was observed in patients with acquired resistance to EGFR TKIs, while this concordance was 94% for the p.T790M mutation, with NGS being able to detect this mutation in three 3 additional patients. CONCLUSIONS: This study indicates the feasibility of circulating tumor nucleic acids (ctNA) analysis as a tumor biopsy surrogate in clinical practice for NSCLC personalized treatment decision making. The use of new sensitive NGS techniques can reliably detect tumor-derived mutations in liquid biopsy and provide clinically relevant information both before and after targeted treatment in patients with NSCLC. Thus, it could aid physicians in treatment decision making in clinical practice.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Tomada de Decisão Clínica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Medicina de Precisão/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Éxons/genética , Estudos de Viabilidade , Feminino , Humanos , Biópsia Líquida , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissues. Furthermore, the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel was used for fusion RNA transcript analysis. The mutation spectrum of the tumors was determined in a cohort of 502 patients with NSCLC using the aforementioned targeted gene panels. The panel used for tumor DNA analysis in this study exhibited high rates (100%) of sensitivity, specificity and reproducibility at a mutation allelic frequency of 3%. At least one DNA mutation was detected in 374 patients (74.5%) and an RNA fusion was identified in 16 patients, (3.2%). In total, alterations in a cancer-driver gene were identified (including point mutations, gene rearrangements and MET amplifications) in 77.6% of the tumors tested. Among the NSCLC patients, 23% presented a mutation in a gene associated with approved or emerging targeted therapy. More specifically, 13.5% (68/502) presented a mutation in a gene with approved targeted therapy (EGFR, ALK, ROS1) and 9.4% (47/502) had an alteration in a gene related to emerging targeted therapies (ERBB2, BRAF, MET and RET). Furthermore, 51.6% of the patients had a mutation in a gene that could be related to an off label therapy or indicative for access to a clinical trial. Thus, the targeted NGS panel used in this study is a reliable approach for tumor molecular profiling and can be applied in personalized treatment decision making for NSCLC patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Mutação , Análise de Sequência de DNA/métodos , Feminino , Redes Reguladoras de Genes , Predisposição Genética para Doença , Humanos , Masculino , Terapia de Alvo MolecularRESUMO
OBJECTIVES: Treatment decision-making in colorectal cancer is often guided by tumour tissue molecular analysis. The aim of this study was the development and validation of a high-resolution melting (HRM) method for the detection of KRAS, NRAS and BRAF mutations in Greek and Romanian patients with colorectal cancer and determination of the frequency of these mutations in the respective populations. SETTING: Diagnostic molecular laboratory located in Athens, Greece. PARTICIPANTS: 2425 patients with colorectal cancer participated in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: 2071 patients with colorectal cancer (1699 of Greek and 372 of Romanian origin) were analysed for KRAS exon 2 mutations. In addition, 354 tumours from consecutive patients (196 Greek and 161 Romanian) were subjected to full KRAS (exons 2, 3 and 4), NRAS (exons 2, 3 and 4) and BRAF (exon 15) analysis. KRAS, NRAS and BRAF mutation detection was performed by a newly designed HRM analysis protocol, followed by Sanger sequencing. RESULTS: KRAS exon 2 mutations (codons 12/13) were detected in 702 of the 1699 Greek patients with colorectal carcinoma analysed (41.3%) and in 39.2% (146/372) of the Romanian patients. Among the 354 patients who were subjected to full KRAS, NRAS and BRAF analysis, 40.96% had KRAS exon 2 mutations (codons 12/13). Among the KRAS exon 2 wild-type patients 15.31% harboured additional RAS mutations and 12.44% BRAF mutations. The newly designed HRM method used showed a higher sensitivity compared with the sequencing method. CONCLUSIONS: The HRM method developed was shown to be a reliable method for KRAS, NRAS and BRAF mutation detection. Furthermore, no difference in the mutation frequency of KRAS, NRAS and BRAF was observed between Greek and Romanian patients with colorectal cancer.