Surgical intervention for lung cancer in patients aged 75 and above: potential associations with increased mortality rates-a single-center observational study.

BACKGROUND: Lung cancer, which is diagnosed two to three times more frequently in patients over the age of 70, is a leading cause of cancer-specific mortality. Given the elevated risk of morbidity and mortality, surgical intervention may not always be the most appropriate primary treatment option. This study aims to evaluate specific risk factors associated with postoperative morbidity and mortality in elderly patients and to optimize patient selection therefore improving surgical outcomes. PATIENTS AND METHODS: The study encompassed a cohort of 73 patients aged 75 and above who underwent surgical treatment for non-small cell lung cancer (NSCLC) at the Department of Thoracic Surgery of the P. Hertsen Moscow Oncological Research Institute between 2015 and 2021. All patients underwent preoperative evaluation, including PET/CT staging and functional assessment, carried out by a multidisciplinary team comprising thoracic surgeons, anesthesiologists, and other medical specialists. RESULTS: The investigation revealed a postoperative mortality rate of 5.5% and a postoperative morbidity incidence of 16.4%, with occurrences of atrial fibrillation in 41.6%, persistent air leak in 33.3%, and pneumonia in 25% of complicated cases. At the one-year follow-up, 88% of patients remained free from relapse, whereas at three years, this rate stood at 66%. During the follow-up period, 16 patients (22%) passed away, with a median survival duration of 44 months. Survival rates at one year, three years, and five years were 71%, 66%, and 35%, respectively. Multivariate analysis disclosed several significant factors predicting a complex postoperative period, including stage IIIb (p = 0.023), pN1 (p = 0.049), pN2 (p = 0.030), and central location (p = 0.007). Additionally, overall survival was primarily influenced by a Charlson comorbidity index of 6 (p = 0.044), stage Ia2 (p = 0.033), and the necessity for thoracotomy (p = 0.045). CONCLUSION: Each case of lung cancer in patients aged 75 and older necessitates an individualized approach. Given the higher mortality rate relative to younger patients, comprehensive risk assessment and preoperative management of underlying comorbidities are imperative, with the involvement of anesthesiologists, intensive care physicians, cardiologists, and other relevant specialists as needed.

Predictive model for intraoperative decision-making in video-assisted thoracoscopic lobectomy: optimizing chest drain placement for high-risk patients.

Background: For years, it has been the common and widely accepted practice in thoracic surgery to place apical and basal drains after a lobectomy to completely drain the pleural cavity. With the development of thoracoscopic technology, it became apparent that the use of a single chest tube provided the same clinical results. However, sometimes tension pneumothorax occurs with the need for additional pleural drainage. The aim of this study was to develop a prognostic model to identify high risk patients intraoperatively and to insert additional pleural drainage to prevent the development of pneumothorax after video-assisted thoracoscopic surgery (VATS) lobectomy. Methods: This was a retrospective multicenter study of patients (registry data was analyzed) who underwent VATS lobectomy via a standardized multiport approach between 2014 and 2022. In all cases, a single drain was used postoperatively. We used a machine learning algorithm and data synthesis to expand patient selection according to Riley's method. A total of 418 cases were analyzed in this study. After determining the prognostically significant factors, we performed a binary logistic regression analysis using reverse step-by-step inclusion of variables according to the Akaike information criterion. After validation of the model by bootstrap (400 iterations) and with the original dataset, a nomogram with a specific point distribution for each risk factor was created. Results: The rate of tension pneumothorax was 4.53% (n=66). The most significant variables associated with the need for additional drainage were adhesions, intraoperative lung suturing, fused interlobar fissure, enlarged intrapulmonary lymph nodes, chronic obstructive pulmonary disease (P<0.001). The C-index of the model was 0.957, the mean absolute calibration error was 0.6%, and the slope of the calibration curve was 0.959. A score of 26 points indicated a 95% risk of postoperative tension pneumothorax. Conclusions: The nomogram achieved good predictive performance for tension pneumothorax after minimally invasive lobectomy. High-risk patients could be identified, and additional drainage may be placed intraoperatively to reduce the risk of lung collapse in the postoperative period.

The Prognostic and Therapeutic Potential of DNA Damage Repair Pathway Alterations and Homologous Recombination Deficiency in Lung Cancer.

Lung cancer remains the second most commonly diagnosed cancer worldwide and the leading cause of cancer-related mortality. The mapping of genomic alterations and their role in lung-cancer progression has been followed by the development of new therapeutic options. Several novel drugs, such as targeted therapy and immunotherapy, have significantly improved outcomes. However, many patients with lung cancer do not benefit from existing therapies or develop progressive disease, leading to increased morbidity and mortality despite initial responses to treatment. Alterations in DNA-damage repair (DDR) genes represent a cancer hallmark that impairs a cell's ability to prevent deleterious mutation accumulation and repair. These alterations have recently emerged as a therapeutic target in breast, ovarian, prostate, and pancreatic cancers. The role of DDR alterations remains largely unknown in lung cancer. Nevertheless, recent research efforts have highlighted a potential role of some DDR alterations as predictive biomarkers of response to treatment. Despite the failure of PARP inhibitors (main class of DDR targeting agents) to improve outcomes in lung cancer patients, there is some evidence suggesting a role of PARP inhibitors and other DDR targeting agents in benefiting a distinct subset of lung cancer patients. In this review, we will discuss the existing literature on DDR alterations and homologous recombination deficiency (HRD) state as predictive biomarkers and therapeutic targets in both non-small cell lung and small cell lung cancer.

Signaling pathways and therapeutic approaches in glioblastoma multiforme (Review).

Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor and is associated with a poor clinical prognosis. Despite the progress in the understanding of the molecular and genetic changes that promote tumorigenesis, effective treatment options are limited. The present review intended to identify and summarize major signaling pathways and genetic abnormalities involved in the pathogenesis of GBM, as well as therapies that target these pathways. Glioblastoma remains a difficult to treat tumor; however, in the last two decades, significant improvements in the understanding of GBM biology have enabled advances in available therapeutics. Significant genomic events and signaling pathway disruptions (NF­κB, Wnt, PI3K/AKT/mTOR) involved in the formation of GBM were discussed. Current therapeutic options may only marginally prolong survival and the current standard of therapy cures only a small fraction of patients. As a result, there is an unmet requirement for further study into the processes of glioblastoma pathogenesis and the discovery of novel therapeutic targets in novel signaling pathways implicated in the evolution of glioblastoma.