RESUMO
INTRODUCTION: Lung cancer is a leading cause of cancer-related mortality in North America. In addition to tobacco smoking, inherited genetic factors can also influence the development of lung cancer. These genetic factors may lead to biologically distinct subsets of cancers that have different outcomes. We evaluated whether genetic sequence variants (GSVs) associated with lung cancer risk are associated with overall survival (OS) and progression-free survival (PFS) in stage-III-IV non-small-cell lung cancer (NSCLC) patients. METHODS: A total of 20 candidate GSVs in 12 genes previously reported to be associated with lung cancer risk were genotyped in 564 patients with stage-III or IV NSCLC. Multivariate Cox proportional hazard models adjusted for potential clinical prognostic factors were generated for OS and PFS. RESULTS: After taking into account multiple comparisons, one GSV remained significant: rs4975616 on chromosome 5p15.33, located near the TERT-CLPTM1L gene. The adjusted hazard ratio (aHR) for OS was 0.75 (0.69-0.91), p = 0.002; for PFS aHR was 0.74 (0.62-0.89), p < 0.001 for each protective variant allele. Results were similar in both Stage III (OS: aHR = 0.70; PFS: aHR = 0.71) and Stage IV patients (OS: aHR = 0.81; PFS: aHR = 0.77). CONCLUSION: A GSV on 5p15.33 is not only a risk factor for lung cancer but may also be associated with survival in patients with late stage NSCLC. If validated, GSVs may define subsets of patients with different risk and prognosis of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Cromossomos Humanos Par 5/genética , Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Loci Gênicos , Variação Genética , Genótipo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Telomerase/genéticaRESUMO
OBJECTIVES: A comprehensive geriatric assessment (CGA) is an objective means of assessing the global health of older patients. While evidence suggesting its promise in improving outcome prediction in the oncology setting is growing, its benefit in guiding treatment decisions remains uncertain. We sought to determine the feasibility and impact of CGA, from a consultative geriatric-oncology service, on treatment decisions in older cancer patients. METHODS: A pilot clinic, where patients underwent CGA with a medical oncologist and geriatrician, was established. Patients ≥70 years, with gastrointestinal or lung cancer were eligible. Following standard assessment by the primary oncologist, a treatment decision was recorded. Patients subsequently underwent a CGA. The final treatment plan was made by the primary oncologist after receipt of findings and recommendations from the CGA. Changes in treatment decisions were recorded. RESULTS: The study enrolled from January to October 2009. Of 168 eligible patients, 120 (71%) were not referred for assessment. Thirty of 48 patients approached underwent CGA. In six patients the treatment plan was undecided at time of referral. In five of these, CGA impacted the ultimate decision (83%). Where the management plan was decided at time of referral (n=24), CGA impacted the final decision in only 1 patient (4%). Previously unidentified medical problems were identified in 70% of patients. CONCLUSIONS: Several factors limited the feasibility of a consultation-type geriatric-oncology service to assess older cancer patients. The impact of CGA in informing treatment decisions was modest but may be of value when the initial treatment decision is uncertain.
