RESUMO
Background: Lung cancer represents a significant global health concern, often diagnosed in its advanced stages. The advent of massive DNA sequencing has revolutionized the landscape of cancer treatment by enabling the identification of target mutations and the development of tailored therapeutic approaches. Unfortunately, access to DNA sequencing technology remains limited in many developing countries. In this context, we emphasize the critical importance of integrating this advanced technology into healthcare systems in developing nations to improve treatment outcomes. Methods: We conducted an analysis of electronic clinical records of patients with confirmed advanced non-small cell lung cancer (NSCLC) and a verified negative status for the epidermal growth factor receptor (EGFR) mutation. These patients underwent next-generation sequencing (NGS) for molecular analysis. We performed descriptive statistical analyses for each variable and conducted both univariate and multivariate statistical analyses to assess their impact on progression-free survival (PFS) and overall survival (OS). Additionally, we classified genetic mutations as actionable or non-actionable based on the European Society for Medical Oncology Scale of Clinical Actionability of Molecular Targets (ESCAT) guidelines. Results: Our study included a total of 127 patients, revealing the presence of twenty-one distinct mutations. The most prevalent mutations were EGFR (18.9%) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (15.7%). Notably, anaplastic lymphoma kinase (ALK) [hazard ratio (HR): 0.258, P<0.001], tumor mutation burden (TMB) (HR: 2.073, P=0.042) and brain magnetic resonance imaging (MRI) (HR: 0.470, P=0.032) demonstrated statistical significance in both the univariate and multivariate analyses with respect to PFS. In terms of OS, ALK (HR: 0.285, P<0.001) and EGFR (HR: 0.482, P=0.024) exhibited statistical significance in both analyses. Applying the ESCAT classification system, we identified actionable genomic variations (ESCAT level-1), including EGFR, ALK, breast cancer (BRAF) gene, c-ros oncogene 1 (ROS1), and rearranged during transfection (RET) gene, in 32.3% of the patients. Conclusions: Our findings from massive DNA sequencing underscore that 32.3% of patients who test negative for the EGFR mutation possess other targetable mutations, enabling them to receive personalized, targeted therapies at an earlier stage of their disease. Implementing massive DNA sequencing in developing countries is crucial to enhance survival rates among NSCLC patients and guide more effective treatment strategies.
RESUMO
Background: Primary thoracic sarcomas (PTS) including primary pulmonary and chest wall sarcomas (CWS), are aggressive lung malignancies with limited information specially in an advanced/unresectable setting. Unfortunately, prognostic factors for these malignancies are not well identified. Methods: Retrospective cohort analysis of patients diagnosed with unresectable/advanced soft tissue PTS from a third level reference institute. Univariate and multivariate analysis performed via Cox-regression model. Progression-free survival (PFS) and overall survival (OS) analysis via Kaplan-Meier method. Results: A total of 157 patients were identified, 55.4% female, mean age 51.8 years (range, 18-90 years), 19.1% tobacco exposure and 10.8% asbestos exposure. The most common performance status was Eastern Cooperative Oncology Group (ECOG) 1 (38.9%), most common clinical presentation cough (58.4%) and thoracic pain (55.4%). Undifferentiated sarcoma (37.6%) followed by synovial sarcoma (34.4%) were the most common histologies. Most patients received five chemotherapeutic cycles (37.6%), 57.3% of patients obtained a partial response and 61.1% an overall response rate (ORR). Median PFS was 9 months [95% confidence interval (CI): 8.717-9.283 months]. The multivariable analysis identified ECOG ≥2, a poorer response to chemotherapy (less number of chemotherapy cycles) and an increase Response Evaluation Criteria in Solid Tumors (RECIST) to be associated with a shorter progression-free period. Median OS was 11 months (95% CI: 10.402-11.958 months) with an ECOG ≥2 and a poorer response to chemotherapy (less number of chemotherapy cycles) associated with a shorter survival. Conclusions: Age, gender, comorbidities, tobacco and asbestos exposure, clinical presentation and histopathological diagnosis are not useful prognostic factors in unresectable/advanced PTS, however, an adequate initial ECOG, RECIST and a better response to chemotherapy should be used as prognostic factors in the management of these tumors.
