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Background: The therapeutic landscape for non-small-cell lung cancer (NSCLC) patients that have common epidermal growth factor receptor (EGFR) mutations has changed radically in the last decade. The availability of these treatment options has an economic impact, therefore a budget impact analysis was performed., Methods: A budget impact analysis was conducted from a Dutch healthcare perspective over a 5-year time horizon in EGFR-mutant NSCLC patients receiving first-line afatinib (Gilotrif ® ) versus first-line osimertinib (Tagrisso ® ), followed by subsequent treatments. A decision analysis model was constructed in Excel. Scenario analyses and one-way sensitivity analysis were used to test the models' robustness., Results: Sequential treatment with afatinib versus first-line treatment with osimertinib showed mean total time on treatment (ToT) of 29.1 months versus 24.7 months, quality-adjusted life months (QALMs) of 20.2 versus 17.4 with mean cost of €108,166 per patient versus €143,251 per patient, respectively. The 5-year total budget impact was €110.4 million for the afatinib sequence versus €158.6 million for the osimertinib sequence, leading to total incremental cost savings of €48.15 million., Conclusions: First-line afatinib treatment in patients with EGFR-mutant NSCLC had a lower financial impact on the Dutch healthcare budget with a higher mean ToT and QALM compared to osimertinib sequential treatment.

Birt-Hogg-Dubé syndrome is associated with an increased risk for renal cell carcinoma. Surveillance is recommended, but the optimal imaging method and screening interval remain to be defined. The main aim of our study was to evaluate the outcomes of RCC surveillance to get insight in the safety of annual US in these patients. Surveillance data and medical records of 199 patients with Birt-Hogg-Dubé syndrome were collected retrospectively using medical files and a questionnaire. These patients were diagnosed in two Dutch hospitals and data were collected until June 2014. A first screening for renal cell carcinoma was performed in 172/199 patients (86%). Follow-up data were available from 121 patients. The mean follow-up period per patient was 4.2 years. Of the patients known to be under surveillance, 83% was screened at least annually and 94% at least every two years. Thirty-eight renal cell carcinomas had occurred in 23 patients. The mean age at diagnosis of the first tumour was 51. Eighteen tumours were visualized by ultrasound. Nine small tumours (7-27 mm) were visible on MRI or CT and not detected using ultrasound. Our data indicate that compliance to renal screening is relatively high. Furthermore, ultrasound might be a sensitive, cheap and widely available alternative for MRI or part of the MRIs for detecting clinically relevant renal tumours in BHD patients,but the limitations should be considered carefully. Data from larger cohorts are necessary to confirm these observations., Competing Interests: The authors have declared that no competing interests exist.

It is unclear to what extent the same set of environmental or genetic factors regulate objective intermediate asthma phenotypes. We examined heritabilities of these phenotypes and estimated their environmental and genetic overlap. We studied baseline lung function (forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC), bronchial hyperresponsiveness, number of positive skin prick tests (SPT) to 11 allergens, serum total immunoglobulin (Ig)E, number of positive specific IgE tests to four allergens and eosinophil counts. 103 twin pairs were studied (46 monozygotic and 57 dizygotic; mean age: 22.5 yrs, range: 17.0-27.0 yrs). Univariate and bivariate genetic analyses were performed after adjustment for significant covariates. All intermediate asthma phenotypes showed significant heritabilities (47-83%). Most phenotypes were substantially correlated, which was mainly due to shared genetic factors. Pairs of phenotypes with the largest genetic correlations were specific IgE and SPT (0.98), and total IgE with specific IgE (0.87), with SPT (0.72), and with eosinophils (0.62). SPT showed significant environmental correlations with total IgE (0.65), specific IgE (0.70) and bronchial hyperresponsiveness (0.44). Genetic effects explain the majority of the variation in objective intermediate asthma phenotypes. Additionally, correlations between pairs of these traits are also mainly explained by genetic rather than environmental factors.

The treatment of Pancoast tumours has been a combined-modality effort for several decades. In a recent Dutch publication, the results in 36 patients are described with a mean follow-up of 26 months. These are in line with internationally-achieved outcomes: the overall and disease-free survival after 2 years was 45 and 31%, respectively, and after 5 years 28 and 19%. As such, the approach to superior-sulcus tumours is a very good example of how the modern treatment of lung cancer has developed, and it underlines the need for close collaboration between specialists with different backgrounds. The patients will benefit from centralisation of the treatment in a limited number of institutions in the Netherlands.

Background: For patients with early-stage lung cancer (ESLC) and severe comorbidities, the cost-effectiveness of early intervention may be reduced by screening and treatment-related morbidity and mortality in addition to the risk for non-cancer-related deaths., Objectives: The use of bronchoscopic treatment (BT) for centrally located ESLC as minimally invasive technique has raised questions whether this approach will be more cost-effective than standard surgical resection in the above-mentioned cohort of patients., Methods: The cost-effectiveness of BT of 32 medically inoperable patients with intraluminal tumor has been compared to a matched control group of surgically treated stage IA cancer patients., Results: Median follow-up after BT for ESLC has been 5 years (range 2-10) versus 6.7 years (range 2-10) for the surgical group. Five patients (16%) developed subsequent primaries/local recurrences after BT versus 4 (12.5%) in the surgical group. The respective percentages of actual survival during follow-up have been 50 and 41%, non-lung-cancer-related death 22 and 31% and lung-cancer-related death 28% in both groups, respectively. So far, the average costs per individual for early management by BT have been Euro 22,638 by surgery, and total expenses have been Euro 209,492 and Euro 724,403, respectively., Conclusions: Despite the worse initial health status of patients treated with BT, actual survival rates and costs for early intervention underscore the superior cost-effectiveness of BT as early intervention in properly selected individuals with ESLC in the central airways., (Copyright 2004 S. Karger AG, Basel)

Background: Patients with locally advanced non-small cell lung cancer (NSCLC) may be treated with induction chemotherapy (IC) followed by surgery with curative intent. The impact of staging inaccuracies on the failure rate of this intensive combined modality treatment approach, i.e. non-curative chemotherapy and thoracotomy, requires further investigation., Methods: The records of a cohort of 38 consecutive NSCLC IIIA-N2 patients treated with IC followed by surgery were reviewed., Results: The clinical course strongly suggested that the standard diagnostic algorithm failed to demonstrate stage IV disease in 34% of the cases. Surgery instigated by CT-based response criteria at restaging after chemotherapy proved to be irradical in 70% of cases., Conclusion: Our data confirm the limitations of the current work-up of patients with apparently locally advanced NSCLC. This applies to the selection of patients to be assigned to combined modality treatment as well as to the post-chemotherapy assessment of resectability. Improved (re)staging of these patients will enhance the efficiency of intervention trials and prevent patients from being exposed to intensive and toxic therapy from which they derive no benefit.

Background: A study was undertaken to investigate the clinical practice, yield, and costs of preoperative staging in patients with suspected NSCLC and to obtain baseline data for prospective studies on the cost effectiveness of (18)F-fluorodeoxyglucose positron emission tomography in the management of these patients., Methods: A retrospective study of the medical records of all patients with suspected NSCLC was performed during a 2 year interval (1993-4) in an academic and a large community hospital., Results: Three hundred and ninety five patients with suspected NSCLC were identified; 58 were deemed to be medically inoperable and 337 patients proceeded to the staging process. Staging required a mean (SD) of 5.1 (1.5) diagnostic tests per patient (excluding thoracotomy) carried out over a median period of 20 days (IQR 10-31). Many of the tests (including both invasive and non-invasive) were done because previous imaging tests had suggested metastases, and in most cases the results of initial tests proved to be false positives. After clinical staging, 168 patients were considered to be resectable (stage I/II) and 144 patients underwent surgery with curative intent. At surgery 33 patients (23% of those who underwent surgery) were found to have irresectable lesions and 19 (13%) had a benign lesion. Surgery was also considered to be futile in 22 patients (15%) who developed metastases or local recurrence within 12 months following radical surgery. Hospital admission was responsible for most of the costs., Conclusion: In many patients staging involved considerable effort in terms of the number of diagnostic tests, the duration of the staging period and the cost, with limited success in preventing futile surgery. Failures relate to the quality of diagnostic preparation at every level of the TNM staging system.

In The Netherlands, the 'Dutch consensus strategy' was formulated in 1993 as a diagnostic strategy for patients with suspected pulmonary embolism. Four years after its introduction, the application of this strategy was investigated. A questionnaire was sent to the hospital management and the departments of internal medicine and pulmonology of all Dutch hospitals. In total, 384 questionnaires were sent out. The response rates of the internists and pulmonologists were 63 and 65%, respectively. The specialists reported to have followed the consensus strategy in 75% of the patients seen the month prior to the questionnaire. However, analysis of only the last patient with the suspicion of pulmonary embolism revealed that the consensus strategy was followed in 55 of the 162 patients. As well, an overuse and an underuse of the different diagnostic facilities was documented. Furthermore almost a quarter of the patients were treated without an ascertained diagnosis, whereas 11% were not treated despite an improper exclusion of venous thrombo-embolism. Compared to a survey in 1994, the use of the 'Dutch consensus strategy' has not improved dramatically. In 34% of the patients, the consensus strategy was strictly followed (i.e. without any additional investigation); however in 67% of the patients a proper diagnosis was achieved. In any diagnostic strategy, two aspects should be considered. First the availability of the different facilities. Second the acceptance of the strategy by the physicians, involved in the diagnosis of patients with clinically suspected pulmonary embolism.

Pulmonary embolism remains a complex diagnostic problem. Although accurate and cost-effective, the 'Dutch consensus' strategy is not widely applied. We assessed the availability and investment plans of the different facilities used in this strategy. Furthermore, the current and future availability of new diagnostic modalities was investigated. A questionnaire was sent to all Dutch hospitals. The questionnaire contained separate sections with questions for the hospital management and the medical practitioners at the departments of radiology, nuclear medicine, internal medicine and pulmonology. Five hundred and eighty-four questionnaires were sent out (response rate 68%). Forty-three percent of the hospitals had no nuclear medicine facility, 11% had no pulmonary angiography facility, and 59% had no spiral CT scan (SCTA). Forty-six percent of the responding hospitals had a nuclear medicine facility; and 5% used Technegas for ventilation studies. Strategies with SCTA were available in about 27% of the hospitals. Due to future investments this number will increase to approximately 55%. Strategies with Technegas were available in 2.4% of the hospitals, this number might increase to 25% if Technegas is proven accurate. The 'Dutch consensus' strategy is available in two-thirds of the hospitals. All other strategies were less feasible. Several equivalent strategies for diagnosing pulmonary embolism should be developed. These strategies should be accurate, widely available and accepted.

Study Aims: To examine the influence of atmospheric pressure (AP) and temperature changes on the incidence of idiopathic spontaneous pneumothorax (SP)., Methods: From December 1991 through November 1993, 115 consecutive SP cases were selected. Patients were included after being in Amsterdam at least 1 full day before contracting the SP. Differences in air temperature and AP (provided hourly by the national weather bureau) for the days of the SP occurrence and the days previous to it were recorded to measure influences of air temperature and AP. The correlation between days with lightning and SP and clustering of SP was evaluated., Results: SP occurred on 14.7% of the days in the 2-year period. There was no relationship between SP and a rise or fall in AP (Poisson regression). There was an average temperature rise of 0.57 degrees C from the day prior to the day of the SP, compared with a 0.08 degrees C fall on the days without SP. This difference is statistically significant and was consistent over the four seasons and both years. Seventy-three percent of the SP cases were clustered. A relationship between SP and thunderstorms was found., Conclusions: AP differences do not seem to influence the chance of developing SP. SP occurs in clusters, and more often 1 to 2 days after thunderstorms. Whether the identified temperature rise prior to the SP is a causative factor is unlikely; coexisting weather phenomena might explain this unexpected finding and should be studied in the future.