Mutation profile in liquid biopsy tested by next generation sequencing in Mexican patients with non-small cell lung carcinoma and its impact on survival.

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.

Survival prognostic factors in unresectable/advanced primary thoracic sarcomas.

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.

Non-operative management versus operative management in high-grade blunt hepatic injury.

BACKGROUND: Surgery used to be the treatment of choice in cases of blunt hepatic injury, but this approach gradually changed over the last two decades as increasing non-operative management (NOM) of splenic injury led to its use for hepatic injury. The improvement in critical care monitoring and computed tomographic scanning, as well as the more frequent use of interventional radiology techniques, has helped to bring about this change to non-operative management. Liver trauma ranges from a small capsular tear, without parenchymal laceration, to massive parenchymal injury with major hepatic vein/retrohepatic vena cava lesions. In 1994, the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma (AAST) revised the Hepatic Injury Scale to have a range from grade I to VI. Minor injuries (grade I or II) are the most frequent liver injuries (80% to 90% of all cases); severe injuries are grade III-V lesions; grade VI lesions are frequently incompatible with survival. In the medical literature, the majority of patients who have undergone NOM have low-grade liver injuries. The safety of NOM in high-grade liver lesions, AAST grade IV and V, remains a subject of debate as a high incidence of liver and collateral extra-abdominal complications are still described. OBJECTIVES: To assess the effects of non-operative management compared to operative management in high-grade (grade III-V) blunt hepatic injury. SEARCH METHODS: The search for studies was run on 14 April 2014. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), PubMed, ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registries, conference proceedings, and we screened reference lists. SELECTION CRITERIA: All randomised trials that compare non-operative management versus operative management in high-grade blunt hepatic injury. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to relevant study reports. We used standard methodological procedures as defined by the Cochrane Collaboration. MAIN RESULTS: We were unable to find any randomised controlled trials of non-operative management versus operative management in high-grade blunt hepatic injury. AUTHORS' CONCLUSIONS: In order to further explore the preliminary findings provided by animal models and observational clinical studies that suggests there may be a beneficial effect of non-operative management versus operative management in high-grade blunt hepatic injury, large, high quality randomised trials are needed.

Thromboprophylaxis for trauma patients.

BACKGROUND: Trauma is a leading causes of death and disability in young people. Venous thromboembolism (VTE) is a principal cause of death. Trauma patients are at high risk of deep vein thrombosis (DVT). The incidence varies according to the method used to measure the DVT and the location of the thrombosis. Due to prolonged rest and coagulation abnormalities, trauma patients are at increased risk of thrombus formation. Thromboprohylaxis, either mechanical or pharmacological, may decrease mortality and morbidity in trauma patients who survive beyond the first day in hospital, by decreasing the risk of VTE in this population.A previous systematic review did not find evidence of effectiveness for either pharmacological or mechanical interventions. However, this systematic review was conducted 10 years ago and most of the included studies were of poor quality. Since then new trials have been conducted. Although current guidelines recommend the use of thromboprophylaxis in trauma patients, there has not been a comprehensive and updated systematic review since the one published. OBJECTIVES: To assess the effects of thromboprophylaxis in trauma patients on mortality and incidence of deep vein thrombosis and pulmonary embolism. To compare the effects of different thromboprophylaxis interventions and their effects according to the type of trauma. SEARCH METHODS: We searched The Cochrane Injuries Group Specialised Register (searched April 30 2009), Cochrane Central Register of Controlled Trials 2009, issue 2 (The Cochrane Library), MEDLINE (Ovid) 1950 to April (week 3) 2009, EMBASE (Ovid) 1980 to (week 17) April 2009, PubMed (searched 29 April 2009), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) (1970 to April 2009), ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (1990 to April 2009). SELECTION CRITERIA: Randomized controlled clinical trials involving people of any age with major trauma defined by one or more of the following criteria: physiological: penetrating or blunt trauma with more than two organs and unstable vital signs, anatomical: people with an Injury Severity Score (ISS) higher than 9, mechanism: people who are involved in a 'high energy' event with a risk for severe injury despite stable or normal vital signs. We excluded trials that only recruited outpatients, trials that recruited people with hip fractures only, or people with acute spinal injuries. DATA COLLECTION AND ANALYSIS: Four authors, in pairs (LB and CM, EF and RC), independently examined the titles and the abstracts, extracted data, assessed the risk of bias of the trials and analysed the data. PP resolved any disagreement between the authors. MAIN RESULTS: Sixteen studies were included (n=3005). Four trials compared the effect of any type (mechanical and/or pharmacological) of prophylaxis versus no prophylaxis. Prophylaxis reduced the risk of DVT in people with trauma (RR 0.52; 95% CI 0.32 to 0.84). Mechanical prophylaxis reduced the risk of DVT (RR = 0.43; 95% CI 0.25 to 0.73). Pharmacological prophylaxis was more effective than mechanical methods at reducing the risk of DVT (RR 0.48; 95% CI 0.25 to 0.95). LMWH appeared to reduce the risk of DVT compared to UH (RR 0.68; 95% CI 0.50 to 0.94). People who received both mechanical and pharmacological prophylaxis had a lower risk of DVT (RR 0.34; 95% CI 0.19 to 0.60) AUTHORS' CONCLUSIONS: We did not find evidence that thromboprophylaxis reduces mortality or PE in any of the comparisons assessed. However, we found some evidence that thromboprophylaxis prevents DVT. Although the strength of the evidence was not high, taking into account existing information from other related conditions such as surgery, we recommend the use of any DVT prophylactic method for people with severe trauma.