The role of surgery for stage I non-small cell lung cancer in octogenarians in the era of stereotactic body radiotherapy in the Netherlands

ObjectivesResection is the standard treatment for stage I non-small cell lung cancer (NSCLC) in operable patients. Stereotactic body radiotherapy (SBRT) is recommended for inoperable patients. A shift from surgery to SBRT is expected in elderly patients due to increased frailty and competing risks. We assessed the current influence of age on treatment decision-making and overall survival (OS).Materials and methodsWe performed a retrospective cohort study using data from patients with clinical stage I NSCLC diagnosed in 2012–2016 and treated with lobectomy, segmentectomy, wedge resection, or SBRT, retrieved from the Netherlands Cancer Registry. Patient characteristics and OS were compared between SBRT and (sub)lobar resection for patients aged 18−79 and ≥80 years.Results and Conclusion8764 patients treated with lobectomy (n = 4648), segmentectomy (n = 122), wedge resection (n = 272), or SBRT (n = 3722) were included. In 2012–2016, SBRT was increasingly used for octogenarians and younger patients from 75.3% to 83.7% and from 30.8% to 43.2%, respectively. Five-year OS in the whole population was 70% after surgery versus 39% after SBRT and 50% versus 27% in octogenarians. After correction for age, gender, year of diagnosis, and clinical T-stage, OS was equal after lobectomy and SBRT in the first 2 years after diagnosis. However, after >2 years, OS was better after lobectomy than after SBRT.SBRT is the prevailing treatment in octogenarians with stage I NSCLC. While surgery is associated with better OS than SBRT, factors other than treatment modality (e.g. comorbidity) may have had a significant impact on survival. The wider application of SBRT in octogenarians likely reflects the frailty of this group. Registries and trials are required to identify key determinants of frailty in this specific population to improve patient selection for surgery or SBRT.Stem cells & developmental biolog

Prognostic value of deep learning-mediated treatment monitoring in lung cancer patients receiving immunotherapy

BackgroundCheckpoint inhibitors provided sustained clinical benefit to metastatic lung cancer patients. Nonetheless, prognostic markers in metastatic settings are still under research. Imaging offers distinctive advantages, providing whole-body information non-invasively, while routinely available in most clinics. We hypothesized that more prognostic information can be extracted by employing artificial intelligence (AI) for treatment monitoring, superior to 2D tumor growth criteria.MethodsA cohort of 152 stage-IV non-small-cell lung cancer patients (NSCLC) (73 discovery, 79 test, 903CTs), who received nivolumab were retrospectively collected. We trained a neural network to identify morphological changes on chest CT acquired during patients' follow-ups. A classifier was employed to link imaging features learned by the network with overall survival.ResultsOur results showed significant performance in the independent test set to predict 1-year overall survival from the date of image acquisition, with an average area under the curve (AUC) of 0.69 (p < 0.01), up to AUC 0.75 (p < 0.01) in the first 3 to 5 months of treatment, and 0.67 AUC (p = 0.01) for durable clinical benefit (6 months progression-free survival). We found the AI-derived survival score to be independent of clinical, radiological, PDL1, and histopathological factors. Visual analysis of AI-generated prognostic heatmaps revealed relative prognostic importance of morphological nodal changes in the mediastinum, supraclavicular, and hilar regions, lung and bone metastases, as well as pleural effusions, atelectasis, and consolidations.ConclusionsOur results demonstrate that deep learning can quantify tumor- and non-tumor-related morphological changes important for prognostication on serial imaging. Further investigation should focus on the implementation of this technique beyond thoracic imaging.Pathogenesis and treatment of chronic pulmonary disease

Cardiovascular markers and mediators in human septic shock

Groeneveld, A.B.J. [Promotor]Beishuizen, A. [Copromotor

Feasibility of 3-dimensional video-assisted thoracic surgery (3D-VATS) for pulmonary resection

Contains fulltext : 152230.pdf (publisher's version ) (Open Access)BACKGROUND: Two-dimensional video-assisted thoracic surgery (2D-VATS) has gained its position in daily practise. Although very useful, its two-dimensional view has its drawbacks when performing pulmonary resections. We report our first experience with 3-dimensional video-assisted surgery (3D-VATS). Advantages and differences with 2D-VATS and robotic surgery (RS) are discussed. METHODS: To evaluate feasibility, we scheduled patients for surgery by 3D-VATS who would normally be treated with 2D-VATS. The main difference of the equipment in 3D-VATS compared with former VATS equipment, is the flexible camera-tip (100-degrees) and the necessary 3D-glasses. RESULTS: Four patients were successfully operated for anatomic pulmonary resections. On-the-structure dissection was easily performed and with the flexible camera-tip, a perfect view can be obtained, with clear visualisation of important (hilar) structures. These features highly facilitate the surgeon in tissue preparation and recognition of the dissection planes. CONCLUSION: In our opinion, 3D-VATS is superior to 2D-VATS for performing anatomic pulmonary resection and we expect an improvement in terms of operation time and learning curve. Furthermore, it is a valuable alternative for RS at lower costs

High circulating N-terminal pro-B-type natriuretic peptide is associated with greater systolic cardiac dysfunction and nonresponsiveness to fluids in septic vs nonseptic critically ill patients

Purpose: It is still unclear whether circulating levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) reflect cardiac filling and function in the critically ill patient, particularly during sepsis and a proinflammatory response that may induce NT-proBNP release from the heart. Materials and Methods: We prospectively evaluated the value of NT-proBNP as a marker of cardiac loading, function, and response to fluid loading in 18 septic and 68 nonseptic, critically ill patients in the intensive care unit of a university medical center. Transpulmonary thermal dilution and pressure measurements were done, and plasma NT-proBNP was determined before and after colloid fluid loading. Results: Compared with nonseptic patients, NT-proBNP plasma levels were higher and systolic cardiac function indices were lower in patients with sepsis than those without sepsis. N-terminal pro-B-type natriuretic peptide best related, from all hemodynamic parameters before and after fluid loading, to systolic cardiac function (rather than diastolic filling) variables, independently of confounders such as renal dysfunction (judged from serum creatinine). In addition, a high NT-proBNP (>3467 pg/mL) predicted absence of fluid responsiveness in sepsis only. Conclusions: Our data suggest that an increased circulating NT-proBNP plasma level is an independent marker of greater systolic cardiac dysfunction, irrespective of filling status, and is a better predictor of fluid nonresponsiveness in septic vs nonseptic, critically ill patients. © 2011 Elsevier Inc