In this review, we aim to summarize the most recent data on the surgical management of oligometastatic non-small cell lung cancer (NSCLC).Background: Approximately 60-70% of all patients with NSCLC initially present with advanced stages of cancer at time of diagnosis. These patients are generally treated with chemotherapy, radiation therapy, or a combination of these modalities. Patients with late-stage disease are usually not considered to be amenable for curative-intent treatments due to poor prognoses. Despite advances in systemic therapies, 5-year overall survival rates in these patients remain poor. However, technological advances in imaging modalities and new imaging strategies have substantially increased tumor detection rates and have resulted in a shift towards earlier diagnosis of NSCLC, possibly in stages in which metastatic disease is limited and still treatable.Studies in recent years have shown that there is a distinct group of patients with metastatic lesions at one or a few sites, often referred to as oligometastatic disease, that may have better survival outcomes compared to patients with more disseminated diseases. Furthermore, it is suggested that these patients may benefit from a combination of systemic treatment and local treatment aimed at the metastatic site(s). However, the role of surgery in this setting remains a controversial subject, with many unanswered questions.Methods: The PubMed/MEDLINE database and the Cochrane database were searched to find relevant articles regarding oligometastatic NSCLC. Specifically, articles regarding definitions of oligometastatic disease, oligometastatic tumor biology, diagnosis, and the treatment of oligometastatic disease were identified.Conclusions: Oligometastatic NSCLC represents a wide spectrum of diseases and encompasses a heterogeneous patient population. Current data suggests that local ablative treatment of oligometastatic lesions with surgery or stereotactic body radiation therapy may result in improved overall survival and progression-free survival rates. However, more data from multi-center prospective trials are necessary to shed light on which therapeutic modalities are most suitable for the treatment of oligometastatic NSCLC.Integration of clinical and molecular staging data is necessary to allow for more personalized treatment approaches.
According to the eighth edition of the tumor–node–metastasis classification, stage III non-small cell lung cancer is subdivided into stages IIIA, IIIB, and IIIC. They represent a heterogeneous group of bronchogenic carcinomas with locoregional involvement by extension of the primary tumor and/or ipsilateral or contralateral lymph node involvement. Surgical indications have not been definitely established but, in general, long-term survival is only obtained in those patients in whom a complete resection is obtained. This mini-review mainly focusses on stage IIIA disease comprising patients with locoregionally advanced lung cancers. Different subcategories of N2 involvement exist, which range from unexpected N2 disease after thorough preoperative staging or “surprise” N2, to bulky N2 involvement, mostly treated by chemoradiation, and finally, the intermediate category of potentially resectable N2 disease treated with a combined modality regimen. After induction therapy for preoperative N2 involvement, best surgical results are obtained with proven mediastinal downstaging when a lobectomy is feasible to obtain a microscopic complete resection. However, no definite, universally accepted guidelines exist. A relatively new entity is salvage surgery applied for recurrent disease after full-dose chemoradiation when no other therapeutic options exist. Equally, only a small subset of patients with T4N0-1 disease qualify for surgical resection after thorough discussion within a multidisciplinary tumor board on the condition that a complete resection is feasible. Targeted therapies and immunotherapy have recently become part of our therapeutic armamentarium, and it might be expected that they will be incorporated in current regimens after careful evaluation in randomized clinical trials.
Background Patient-derived organoids are invaluable for fundamental and translational cancer research and holds great promise for personalized medicine. However, the shortage of available analysis methods, which are often single-time point, severely impede the potential and routine use of organoids for basic research, clinical practise, and pharmaceutical and industrial applications. Methods Here, we developed a high-throughput compatible and automated live-cell image analysis software that allows for kinetic monitoring of organoids, named Organoid Brightfield Identification-based Therapy Screening (OrBITS), by combining computer vision with a convolutional network machine learning approach. The OrBITS deep learning analysis approach was validated against current standard assays for kinetic imaging and automated analysis of organoids. A drug screen of standard-of-care lung and pancreatic cancer treatments was also performed with the OrBITS platform and compared to the gold standard, CellTiter-Glo 3D assay. Finally, the optimal parameters and drug response metrics were identified to improve patient stratification. Results OrBITS allowed for the detection and tracking of organoids in routine extracellular matrix domes, advanced Gri3D®-96 well plates, and high-throughput 384-well microplates, solely based on brightfield imaging. The obtained organoid Count, Mean Area, and Total Area had a strong correlation with the nuclear staining, Hoechst, following pairwise comparison over a broad range of sizes. By incorporating a fluorescent cell death marker, intra-well normalization for organoid death could be achieved, which was tested with a 10-point titration of cisplatin and validated against the current gold standard ATP-assay, CellTiter-Glo 3D. Using this approach with OrBITS, screening of chemotherapeutics and targeted therapies revealed further insight into the mechanistic action of the drugs, a feature not achievable with the CellTiter-Glo 3D assay. Finally, we advise the use of the growth rate-based normalised drug response metric to improve accuracy and consistency of organoid drug response quantification. Conclusion Our findings validate that OrBITS, as a scalable, automated live-cell image analysis software, would facilitate the use of patient-derived organoids for drug development and therapy screening. The developed wet-lab workflow and software also has broad application potential, from providing a launching point for further brightfield-based assay development to be used for fundamental research, to guiding clinical decisions for personalized medicine.
The current coronavirus disease 2019 (COVID-19) pandemic has forced healthcare providers worldwide to adapt their practices. Our understanding of the effects of COVID-19 has increased exponentially since the beginning of the pandemic. Data from large-scale, international registries has provided more insight regarding risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and has allowed us to delineate specific subgroups of patients that have higher risks for severe complications. One particular subset of patients that have significantly higher risks of SARS-CoV-2 infection with higher morbidity and mortality rates are those that require surgical treatment for lung cancer. Earlier studies have shown that COVID-19 infections in patients that underwent lung cancer surgery is associated with higher rates of respiratory failure and mortality. However, deferral of cancer treatments is associated with increased mortality as well. This creates difficult situations in which healthcare providers are forced to weigh the benefits of surgical treatment against the possibility of SARS-CoV-2 infections. A number of oncological and surgical organizations have proposed treatment guidelines and recommendations for patients planned for lung cancer surgery. In this review, we summarize the latest data and recommendations for patients undergoing lung cancer surgery in the COVID-19 circumstance.
The optimal treatment of malignant pleural mesothelioma (MPM) has not yet been established and is still under investigation. Surgery is one of the pillars in the multimodality approach with the purpose of removing as much as visible tumor as possible and to relieve symptoms. To date, two major surgical procedures are available for removal or debulking of MPM that is considered to be resectable: [extended (e)] pleurectomy/decortication (P/D) and extrapleural pneumonectomy (EPP). Historically, EPP was regarded as the only way to achieve a macroscopic complete resection. However, in the last years, there is a shift in literature towards (e)P/D as the preferred surgical procedure whenever possible as several retrospective studies and meta-analyses showed a similar or lower long-term survival and higher perioperative mortality and postoperative morbidity in patients who been treated with EPP. On the other hand, no randomizedcontrolled trials regarding surgical treatment with (e)P/D or EPP exist and therefore level A evidence favoring one surgical procedure is lacking. In this review we provide a nuanced and well-considered answer to the question whether EPP is still indicated in the surgical treatment of MPM.
For patients with locally advanced non-small cell lung cancer (NSCLC) or positive N1 nodes, multimodality treatment is indicated. However, the optimal management of patients presenting with ipsilateral positive mediastinal nodes (N2 disease) has not been determined yet. Different treatment regimens consisting of chemotherapy, radiation therapy, and surgery have been proposed and implemented previously. In more recent years, immunotherapy and targeted therapies have been added as therapeutic options. The role of surgery is currently redefined. Recent studies have shown that surgical resection after induction immunotherapy or targeted therapy is feasible and yields good short-term results. In this review, we summarize the latest data on multimodality treatment options for stage IIIA-N2 locally advanced NSCLC, depending on the extent of nodal involvement.
OBJECTIVES The purpose of this study was to assess the quality of video-assisted cervical mediastinoscopy (VACM) in the staging of non-small-cell lung cancer (NSCLC) at the Antwerp University Hospital with a focus on test effectiveness indicators, morbidity and unforeseen pN2 results. METHODS All consecutive VACM workups of cases of NSCLC performed between January 2010 and December 2015 were included to assess overall test quality and effectiveness. Quality assurance was performed in accordance with the recommendations of the European Society of Gastrointestinal Endoscopy and European Society of Thoracic Surgeons (ESTS) where appropriate. RESULTS A total of 168 video-assisted cervical mediastinoscopies were included. A total of 91.7% of the procedures were performed in accordance with the ESTS guideline. An unforeseen pN2 staging was identified in 10 anatomical lung resections (8.6%). Statistical analysis showed no significant association between VACM performed in accordance with the ESTS guideline and the presence of pN2 positive lymph nodes [χ2 (1) = 0.61; P = 0.57] and no association between VACM performed in accordance with the ESTS guideline and overall futile thoracotomy [χ2 (1) = 0.76; P = 0.50]. Calculations revealed a sensitivity of 81.8 [95% confidence interval (CI) 69.1–90.9], specificity of 100%, positive predictive value of 100%, negative predictive value of 91.9% (95% CI 86.6–95.2) and diagnostic accuracy of 94.1% (95% CI 89.33–97.11). CONCLUSIONS Overall, 91.7% of the VACM were performed in accordance with the ESTS guideline. This process resulted in a sensitivity of 81.8%, a negative predictive value of 91.9% and an unforeseen pN2 rate of 8.6%.
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