RESUMO
The aim of our trial was to evaluate the prognostic significance of qualitative ctDNA analysis on different stages of EGFR mutated non-small cell lung cancer (NSCLC) treatment. We included 99 patients amendable for the first line treatment with either gefitinib/erlotinib (n = 87), afatinib (n = 10) or osimertinib (n = 2). Sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 were performed before first dose, after 2 and 4 months of treatment, and on progression. Our analysis showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line tyrosine kinase inhibitors (TKIs) in terms of progression-free and overall survival. When treated with conventional approach, i.e. monotherapy with TKIs, the patients falls into three subgroups based on ctDNA analysis before and after 2 months of treatment. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 - 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 - 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcome of patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do TratamentoRESUMO
Whole-genome expression analysis methods significantly clarified contemporary breast cancer classification. Besides today clinical practice lacks the use of expression methods due to complexity of conduction, analysis and lack of clinical application. Further studies of breast cancer expression characteristics and clinical trials with stratification based of phonotypical features may improve the results of existing anticancer agents. Creation of limited clinically applicable test system, which incorporates all the specific breast cancer subtypes is currently needed.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Neoplasias da Mama/classificação , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , HumanosRESUMO
The outcomes of Gamma Knife radiosurgery for 95 patients with melanoma brain metastases were studied. The majority of the patients (82%) presented multiple metastatic brain lesions. Local control was achieved in 94% of cases. The Kaplan-Maier analyses of life expectancy revealed that median survival after radiosurgical treatment was 6.9 months. The median survival by RTOG RPA class was 18,3 months for class I; 6.9 months for class II and 3.9 months for class III. These results demonstrate that Gamma Knife radiosurgery provides a high level of local control for melanoma brain metastases and may increase the life expectancy.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Melanoma/secundário , Melanoma/cirurgia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Resultado do TratamentoAssuntos
Antineoplásicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Antibióticos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/uso terapêutico , Humanos , Compostos de Platina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Taxoides/uso terapêuticoRESUMO
The authors present first results of investigations of the connexin-26 gene in DNA obtained from peripheral blood of 55 patients operated on for gastric cancer. Gastric cancer patients were found to have carriage of the Cx 26 gene that was reliably associated with the invasive ability of the tumor. Change of the connexin-26 gene in gastric cancer is evidence of an important role of intercellular gap junctions in the arising and development of gastric cancer.