Lung Cancer

Coordinator: Dr. Luis Miguel Seijó Maceiras

Clinical, Biologic and Molecular Determinants of Prognosis in Stage I/IIp Lung Cancer

Lung Cancer (LC) is an important disease on account of a high incidence and severity and its associated mortality. In contrast to the therapeutic response obtained in other solid tumours, the prognosis of LC has improved only slightly in recent decades, with a 5-year survival still below 15%. The typology of LC is defined by pathological criteria differentiate LC as small and non-small cell carcinoma (NSCLC), with the later further classified as adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Immunohistochemical markers are increasingly used for the correct classification of LC, and the proportion of NSCLC cases remaining undifferentiated is currently very low. The incorporation of prognostic molecular markers, such as Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK), have given further insight in the classification of LC, mainly of the adenocarcinoma subtype, and specific treatments have been developed for patients harbouring abnormalities in these genetic markers, which have led to significant changes in treatment regimens currently added to clinical guidelines, justified by the improvement they attain in recurrence rates and survival. A better characterization of LC through molecular patterns in the tumour is needed, and research focusing on this point is expected to attain a significant social impact.

Investigation

The line of LC at CIBERES works in the following areas:

  • Clinical, Biologic and Molecular Determinants of Prognosis in Stage I/IIp Lung Cancer.

The Strategic Project on LC created the IASLC and CIBERES cohorts of surgically-treated patients stage Ip/IIp in the period 2013-15, with baseline and follow-up clinical information, including biological samples from patients in these cohorts in the CIBERES Pulmonary Biobank Platform, for the performance of molecular marker studies. Thought an agreement between CIBERES and the “Red Temática de Investigación Colaborativa en Cancer” (RTIC Cancer) molecular analyses have been started, and tissue microarrays (TMAs) have been distributed to the central laboratories for the performance of biological analysis. Follow-up of these cohorts is scheduled till end 2016 for the IASLC Cohort and till 2021 for the CIBERES Cohort, with the inclusion of this follow-up in the proposed Project, together with the complete statistical analyses of the assessed prognostic and predictive molecular markers. Analyses of a prognostic specific protein signature expression, tissue inflammatory markers and stromal cell markers will be also analysed by immunochemistry. Some genes methylation will be also assessed in tissue samples, and for inflammatory markers in peripheral blood, as potentially prognostic or predictive markers.

 

  • Screening of LC in a cohort of patients with early COPD

The aggressive and heterogeneous nature of LC has prompted to carry out population screening. From 2014, the LC line at CIBERES created the Early COPD Cohort of up to 2000 subjects at risk for LC due to smoking-related COPD. This project will follow enrolment of subjects till end 2016 for a estimated identification of 100 stage I/IIp LC patients who would be surgically treated. Follow-up of the Early-COPD Cohort will continue till 2021, and molecular markers, that showed prognostic or predictive power on the IASLC and CIBERES cohorts, will be tested in this screening cohort for external validity assessment.

 

  • Molecular diagnosis in respiratory samples obtained through semi-invasive techniques

Cytology samples of nodes and tumours in the mediastinum or lobar regions obtained through endobronchial ultrasonography with needle aspiration (EBUS-NA) are the only diagnostic samples available in more than a half of LC. The assessment of molecular markers with potential prognostic and predictive value, in samples obtained through semi-invasive techniques as EBUS-NA, is of main importance, considering that in a significant number of patients these samples are the only ones available for molecular staging.  It is expected to be highly important to obtain molecular information from these samples, and its prognostic power will be determined in patients with stage II-III-IV.

  • Sleep apnea syndrome, as a comorbidity that increases the probability of LC progression, through recurrent hypoxia.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is an important medical condition, which causes significant morbidity and mortality. Intermittent hypoxia is a characteristic of the disease and has been linked to the progression of cancer in animal models, and a link between OSAHS and LC progression has been hypothesized. Home sleep testing and biological sampling will be performed in patients recently diagnosed with LC. Follow-up of LC patients with and without sleep-disordered breathing will contribute to the clarification of the potential influence of OSAHS on LC prognosis. Additionally they will be performed studies of home sleep testing, biological sampling and follow-up in volunteers participating in Early-COPD cohort to determine the prevalence of sleep disordered breathing in this population, and its relationship with the diagnosis of LC at baseline or the follow-up.

Objectives

The general aims in the present project 2016-2019 are:

  1. To identify clinic-molecular variables able to improve the prognostic capacity of TNM staging in LC.
  2. To validate screening approaches able to target early LC in subjects at risk for from general population.
  3. To identify comorbidity-related factors associated with impairments in LC prognosis.
  4. To identify non-invasive sampling techniques able to provide genetic information useful for prognosis.