Marie Florescu

Mutations in NSCLC and their link with lung cancer-associated thrombosis: A case-control study☆

INTRODUCTION The association of venous thromboembolic events (VTE) and lung cancer is highly prevalent. Additionally, the occurrence of a VTE with cancer has been associated with a worse prognosis and a poor quality of life. Underlying cancer biological features such as tumour mutations may contribute to VTE risk and cancer prognosis. Since preclinical data suggest a link between thrombosis and KRAS mutations in tumours, we aimed to validate this association in a patient registry cohort. METHODS A retrospective case control study was performed using the CHUM NSCLC registry. Cases had VTE occurring 6months previous to or after a diagnosis of NSCLC. Diagnosis of VTE (venous thrombosis, pulmonary embolism, and migratory superficial thrombophlebitis) was confirmed by a review of the imaging reports. Controls were patients with NSCLC without thrombosis matched for age and stage (I-IIIA/IIIB-IV). Exclusion criteria included insufficient tissue for KRAS/EGFR mutation analysis or insufficient clinical information. RESULTS Between Jan 2000 and Dec 2009 a total of 57 cases with VTE and 102 controls without VTE were included. The OR for thrombosis in KRAS and EGFR mutated NSCLC patients are respectively 2.67 (1.12-6.42; p=0.014) and 0.99 (0.27-3.48; p=0.99). CONCLUSIONS KRAS mutation is associated with an increased risk of VTE in this NSCLC cohort. These findings are consistent with preclinical studies. Prospective data on VTE rates from clinical trials with molecularly defined NSCLC are needed to confirm these findings.

Factors influencing treatment selection and survival in advanced lung cancer.

PURPOSE Despite numerous breakthrough therapies, inoperable lung cancer still places a heavy burden on patients who might not be candidates for chemotherapy. To identify potential candidates for the newly emerging immunotherapy-based treatment paradigms, we explored the clinical and biologic factors affecting treatment decisions. METHODS We retrospectively reviewed the records of patients diagnosed at our university-affiliated cancer centre between 1 January 2011 and 31 December 2013. Patient demographics, systemic treatment, and survival were examined. RESULTS During the 3-year study period, 683 patients fitting the inclusion criteria were identified. First-line therapy was administered in 49.5% of patients; only 22.4% received further lines of therapy. The main reasons for withholding therapy were poor performance status [ps (43.2%)], rapidly deteriorating ps (31.9%), patient refusal of therapy (20.9%), and associated comorbidities (4%). Older age, the presence of brain metastasis at diagnosis, and non-small-cell histology were also associated with therapeutic restraint. Oncology referrals were infrequent in patients who did not receive therapy (32.2%). Older patients and those with a poor ps experienced superior survival when treatment was administered (hazard ratio: 0.25; 95% confidence interval: 0.16 to 0.38; and hazard ratio: 0.44; 95% confidence interval: 0.23 to 0.87 respectively; p < 0.001). CONCLUSIONS Advanced lung cancer still poses a therapeutic challenge, with a high proportion of patients being deemed unfit for therapy. This issue cannot be resolved until appropriate measures are taken to ensure the inclusion of older patients and those with a relatively poor ps in large clinical trials. Immunotherapy might be interesting in this setting, given that it appears to be more tolerable. Another consequential undertaking would be the deployment of strategies to reduce wait times during the diagnostic process for patients with a high index of suspicion for lung cancer.