Page 24 - MEMOCiberes014-ENG

LUNG CANCER
Coordinator
Dr. Eduard Monsó
Clinical and molecular characterization of early-stage lung cancer
(lc).
LC is an important disease on account of its high incidence and severity, and on the level of associated mortality . In contrast to the response obtained with other solid tumours and despite an enormous research effort, the prognosis for LC has improved only slightly in recent decades, with a 5-year survival less than 15% .
The typology of LC is defined by anatomo-pathological criteria that initially differentiate LC as small cell
carcinoma and NSCLC, with the latter further classified as adenocarcinoma, squamous cell carcinoma and large cell carcinoma . In a proportion of NSCLC cases this differentiation is not possible, with the carcinoma remaining as undifferentiated . Immunohistochemical markers can be used to clarify in part the situation, but uncertainty in the estimation of prognosis and response to treatment is high . The incorporation of prognostic molecular markers, such as epidermal growth factor receptor (EGFR) in tumour cells, which modulates a different therapeutic response when a mutation is present, has led to significant changes in treatment regimens used in NSCLC, which have been incorporated into clinical guidelines .
Early identification of the disease favours the use of therapeutic interventions associated with prolonged survival . The TNM system of staging according to the degree of extension of the primary tumour (T), lymph nodes (N) and metastasis (M) has been and is important, but is imprecise in relation to the prognosis and treatment selection . The percentage variation in survival with the TNM model is only 30%, with each patient’s prognosis depending on poorly known determinants . In fact, in patients considered to have early-stage LC, there has barely been any reduction over the last 30 years in mortality and relapse . In cases that have been resected and staged as Ip, without evidence of lymph node or systemic metastases at baseline, very high rates (35-50%) of mortality or relapse are seen during follow-up . Moreover, despite the benefits seen with the use of platinum-based adjuvant chemotherapy in cases of advanced stages, the available data do not support the use of such treatment in patients with stage IA cancer and show very questionable results in patients with stage IB cancer . It seems clear that TNM staging based on tumour extension conceals in its apparent homogeneity a considerable level of biological heterogeneity of the tumour or tumour- host relationship, which is evidenced in terms of prognosis and prediction.
The inclusion of new predictive molecular variables to the staging of LC could be a promising approach to improve establishment of the prognosis and prediction of treatment response, in addition and complementarily to the TNM; such an approach could be easily incorporated into clinical practice guidelines and could enable alternative therapies to be defined beyond those currently in use . Numerous studies have addressed this problem, with inconclusive or contradictory outcomes . The cause resides in complexity and difficulty of the problem being studied, the methods used, studies with very specific scientific objectives, small case series, and results not validated in independent, external cohorts .
The SP-LC project within the CIBERES CRP aims to produce valid and useful knowledge from specific scientific objectives, avoiding the methodological problems that have placed in question the results of previous studies . The CRP also proposes, in addition to using the GCCP-II-IASLC Cohort, to generate a CIBERES Cohort, a case series of patients diagnosed with LC of squamous or adenocarcinoma cell lineage, and staged post-resection as I/IIp . Samples will include tumour tissue, non-tumorous pulmonary tissue, lymph nodes and peripheral blood, apart from the collection of clinicopathological characteristics of the patient at the time of treatment and following the evolution of patients included in the prospective cohort at two and five years following treatment, with information about disease-free time and survival . This will involve only those hospitals with a thoracic surgery unit and associated with SEPAR (N = 53) .
The CIBERES SP-LC aims to create a cohort of patients diagnosed with LC by screening with LR-CT . An Early
24 CIBERES » Annual report 2014