External validation of NTCP-models for radiation pneumonitis in lung cancer patients treated with chemoradiotherapy.

PURPOSE: Normal tissue complication probability (NTCP) models can be used to estimate the risk of radiation pneumonitis (RP). The aim of this study was to externally validate the most frequently used prediction models for RP, i.e., the QUANTEC and APPELT models, in a large cohort of lung cancer patients treated with IMRT or VMAT. [1-2] METHODS AND MATERIALS: This prospective cohort study, included lung cancer patients treated between 2013 and 2018. A closed testing procedure was performed to test the need for model updating. To improve model performance, modification or removal of variables was considered. Performance measures included tests for goodness of fit, discrimination, and calibration. RESULTS: In this cohort of 612 patients, the incidence of RP ≥ grade 2 was 14.5%. For the QUANTEC-model, recalibration was recommended which resulted in a revised intercept and adjusted regression coefficient (from 0.126 to 0.224) of the mean lung dose (MLD),. The APPELT-model needed revision including model updating with modification and elimination of variables. After revision, the New RP-model included the following predictors (and regression coefficients): MLD (B = 0.250), age (B = 0.049, and smoking status (B = 0.902). The discrimination of the updated APPELT-model was higher compared to the recalibrated QUANTEC-model (AUC: 0.79 vs. 0.73). CONCLUSIONS: This study demonstrated that both the QUANTEC- and APPELT-model needed revision. Next to changes of the intercept and regression coefficients, the APPELT model improved further by model updating and performed better than the recalibrated QUANTEC model. This New RP-model is widely applicable containing non-tumour site specific variables, which can easily be collected.

[Referred with the working diagnosis 'pneumothorax: could it be another diagnosis?]. / Verwezen met de werkdiagnose 'pneumothorax': kan het ook iets anders zijn?

BACKGROUND: Patients who are referred to an emergency department (ED) often have a working diagnosis. Hospital physicians may be inclined to accept this diagnosis and incorrectly link the findings of investigations to it. This may lead to an incorrect definitive diagnosis and therapy. CASE DESCRIPTION: We present the case of a 36-year-old female who was referred to the ED with a pneumothorax seen on chest x-ray. Findings from history-taking, physical examination and a second chest x-ray taken on the ED were diagnosed as being consistent with pneumothorax and a chest-drain was inserted. However, further investigation showed that she had Swyer-James-Mcleod syndrome which could have been treated conservatively. CONCLUSION: This patient was given a chest drain after the working diagnosis of pneumothorax was made. Due to the definite diagnosis of Swyer-James-Mcleod the indication for chest drainage may have been incorrect. If a diagnosis of pneumothorax is suspected, but diagnostic findings suggest otherwise, further investigations should be performed before a chest drain is inserted.

An instrument dedicated for modelling of pulmonary radiotherapy.

BACKGROUND AND PURPOSE: Radiotherapy plays a pivotal role in lung cancer treatment. Selection of patients for new (radio)therapeutic options aiming at improving outcomes requires reliable and validated prediction models. We present the implementation of a prospective platform for evaluation and development of lung radiotherapy (proPED-LUNG) as an instrument enabling multidimensional predictive modelling. MATERIALS AND METHODS: ProPED-LUNG was designed to comprise relevant baseline and follow up data of patients receiving pulmonary radiotherapy with curative intent. Patient characteristics, diagnostic and staging information, treatment parameters including full dose-volume-histograms, tumour control, survival, and toxicity are scored. Besides physician-rated data, a range of patient-rated data regarding symptoms and health-related quality-of-life are collected. RESULTS: After 18 months of accrual, 315 patients have been included (accrual rate, 18 per month). Of the first hundred patients included, 70 received conformal (chemo)radiotherapy and 30 underwent stereotactic radiotherapy. Compliance at 3 and 6 months follow-up was 96-100% for patient-rated, and 81-94% for physician-rated assessments. For data collection, 0.4 FTE were allocated in a 183 FTE department (0.2%). CONCLUSIONS: ProPED-LUNG is feasible with high compliance rates and yields a large amount of high quality prospective disease-related, treatment-related, patient- and physician-rated data which can be used to evaluate new developments in pulmonary radiotherapy.

Reticular basement membrane in asthma and COPD: similar thickness, yet different composition.

BACKGROUND: Reticular basement membrane (RBM) thickening has been variably associated with asthma and chronic obstructive pulmonary disease (COPD). Even if RBM thickness is similar in both diseases, its composition might still differ. OBJECTIVE: To assess whether RBM thickness and composition differ between asthma and COPD. METHODS: We investigated 24 allergic asthmatics (forced expiratory volume in one second [FEV(1)] 92% predicted), and 17 nonallergic COPD patients (FEV(1) 60% predicted), and for each group a control group of similar age and smoking habits (12 and 10 persons, respectively). Snap-frozen sections of bronchial biopsies were stained with hematoxylin/eosin and for collagen I, III, IV, V, laminin and tenascin. RBM thickening was assessed by digital image analysis. Relative staining intensity of each matrix component was determined. RESULTS: Mean (SD) RBM thickness was not significantly different between asthma and COPD 5.5 (1.3) vs 6.0 (1.8) microm, but significantly larger than in their healthy counterparts, ie, 4.7 (0.9) and 4.8 (1.2) microm, respectively. Collagen I and laminin stained significantly stronger in asthma than in COPD. Tenascin stained stronger in asthma than in healthy controls of similar age, and stronger in COPD controls than in asthma controls (p < 0.05). CONCLUSION: RBM thickening occurs both in asthma and COPD. We provide supportive evidence that its composition differs in asthma and COPD.