Leslie Noirez, Laurent P. Nicod Respiratory Medicine Department
Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne
SCHWERPUNKTTHEMA: LUNGENKREBS
Definition of population at risk
In a recent study, the analysis of the NLST population showed that in case of subjects with multiple risk-factors the benefits/harms balance towards LCS is clearly favor-able (11). Subjects should be screened by the criteria speci- fied in the screening protocol according to age, smoking history, duration of smoking cessation, family history and with clear inclusion/exlusion criteria (14, 19). The Ex-pert Panel of Swiss University Hospitals suggests that the screened population should be the same as in the NLST aged 55-74 years with at least 30 pack-years of active or discontinued smoking history for less than 15 years and without clinical symptoms of cancer. Recent studies sug-gest that the selection criteria for LCS could be redefined with extension of the age group, subjects with lower level of smoking exposure, type of occupational exposure and inclusion of subjects with underlying lung disease (e.g COPD, interstitial pulmonary fibrosis) (15). This is not fully supported by the current evidences but progress has been made for example by the Liverpool Lung Project in this field (16).
Lung nodule assessment
Approximatively one cancer may have been caused by ra-diation from CT per 2500 persons screened (10). In the future, technical improvment in CT will lead to a lower ra-diation exposure of approximately 0.2 mSv compared to a current average effective dose of 1.5 mSv with LDCT (20).
Radiation exposure was generated by follow-up scans and derived diagnostic evaluations and may be signifi-cant. This should be included in the monitoring process as the interval between LDCT and the number of rounds.
As mentioned above, only a minor proportion of lung le-sions detected by LDCT will finally turn out to represent early lung cancer (8). In the NSLC 320 patients should be screened to avoid 1 cancer death (4). Studies suggest that LDCT screening for lung cancer may detect small tumors that would never become life-threatening corresponding to the definition of overdiagnosis which represents a poten-tial harm and bias of screening (12) with an estimated rate of more than 18% of all lung cancers detected by LDCT in the NLST (13). It may incur additional costs, investi-gations, morbidity, and anxiety. Management of lung nod-ules should be developed from standardized radiologic de-scription. The Swiss Expert Panel proposed an algorithm outlined in the statement of the National Comprehensive Cancer Network (NCCN) for the management of non solid/solid or partly solid nodules (7, 21-25). The Swiss Expert Panel recommends the use of lung nodule volum-etry in case of standardized CT protocols and the use of the same software for each measurement based on the NEL-SON trial which suggests that volumetry may reduce false positive and false negative rates (9). In another way, stu-
dies have analysed the Computer Assisted lung nodule De-tection (CAD), a validated commercial software designed as a multi-step approach aiming to detect parenchymal le-sions at high sensitivity and specificity focusing on solid lesions larger than 3 mm. It may be prefered to conven-tional double reading because more sensitive in 96.7% vs.
78.1%, respectively (24). These techniques are not widely available yet.
Screening interval
The time interval between CT scans in the screening program has great impact on costs but also on the cu-mulative radiation dose. An increase in the time inter-val may however reduce the diagnostic sensitivity of the screening test. Based on the NLST data at present an-nual screening is recommended. In the NELSON trial a screening interval of 1.2 and 2.5 years is being evalu-ated (26). A two-year interval after baseline scan instead of one annual repeat scan did not impair the diagnosis sensitivity but with a 2.5-year interval the frequency of interval cancers increased significantly (9). The most ap-propriate number of screening rounds is still not deter-mined.
Management of patients and results
Individual management is of crucial importance by a well-trained staff within a well-organised infrastructure for an efficient lung cancer screening program. For a na-tional prospective trial or registry, the Swiss Expert Panel proposes that lung cancer screening should be done only at certified institutions, authorized and accredited to per-form lung cancer screening with the necessary infrastruc-ture and expertise for the multidisciplinary work-up of lung nodules and the management of lung cancers and should be reinforced by health authorities (7, 17, 18). Edu- cation and information for participants and staff are recommended. Smoking cessation should be actively en-couraged and should be integrated in the screening pro-gram involving staff training and certification (17).
Cost and cost-effectiveness
Costs of cancer screening depend mainly on patient se-lection. To avoid unnecessary costs it implies that the population included in the lung screening cancer pro-gram should be defined very carefully. Cost-effectiveness of LDCT screening for lung cancer is a highly debatable issue (27). The financial impact of a screening program suggests other questions such as whether health insur-ances should bear the costs of screening individuals who still are smoking? The NELSON trial results may be de-cisive to avoid unnecessary investigations and thus un-necessary costs. Beyond the costs, the psychological im-pact of unnecessary investigations should be evaluated.
SCHWERPUNKTTHEMA: LUNGENKREBS
In the meantime
Before lung cancer screening can be broadly implemented in clinical practice in Switzerland comparison of practi- ces and outcomes between screening centers is needed to guarantee high quality standards at a national level. More knowledge about the costs for health authorities and for insurance providers too are waiting.
References
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Correspondence:
Dr. Leslie Noirez Service de Pneumologie Endoscopie Interventionnelle
CHUV - Bugnon 46, CH-1011 Lausanne leslie.noirez@chuv.ch
SCHWERPUNKTTHEMA: LUNGENKREBS
Over the past 10 years, the treatment for lung cancer has drastically changed from chemotherapy - as the unique sole modality - to targeted therapies, immunotherapy and refinement of complex multimodality treatments. The de-velopment of targeted therapies and potent agents such as tyrosine kinase inhibitors shifted the therapeutic approach towards personalised medicine, where patients are treated in the context of their driver mutations [1-3].
Immune escape is a critical gateway to malignancy [4].
The recent clinical developments in immunotherapy for lung cancer have improved the outcome of patients with metastatic disease. The multiple natural negative feedback mechanisms that regulate the adaptive immune response, impacting T-cell or natural killer cell functions, offer mul-tiple opportunities for therapeutic intervention [5].
All these developments led to impressive successes in terms of response and survival. Never-theless, lung cancer remains the leading cause of cancer-related mortality worldwide and new treatment options are needed to improve the prognosis for pa-tients with lung cancer [6]. The establishment of the European Thoracic Oncology Platform (ETOP) originated in a group of investigators who shared the vision of improving the treat-ment options and prospective for patients with thoracic ma-lignancies and who had a first informal meeting during the ESMO congress in Stockholm, Sweden in September 2008 [7].
The foundation of ETOP as a not-for-profit organisation under Swiss law and with headquarters in Bern was approved by author-ities in March 2009. Since then, the scientific network of ETOP has continuously grown and