ABSTRACT
BACKGROUND: Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein ß1 (HSPB1) and transforming growth factor ß1 (TGFß1) and survival have been investigated. METHODS: A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFß1 gene and 5 of HSPB1 gene) variables were analyzed. RESULTS: The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFß1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19-8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37-10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98-3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p < 0.001) and DFS (p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. CONCLUSIONS: Genetic analysis showed the CA genotype of TGFß1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.
Subject(s)
Lung Neoplasms/genetics , Polymorphism, Single Nucleotide/genetics , Small Cell Lung Carcinoma/genetics , Transforming Growth Factor beta1/genetics , Adult , Aged , Antineoplastic Agents/therapeutic use , Cranial Irradiation/methods , Disease-Free Survival , Female , Genotype , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/radiotherapy , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Prognosis , Proportional Hazards Models , Prospective Studies , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/radiotherapyABSTRACT
Complete resection continues to be the gold standard for the treatment of early-stage lung cancer. The landmark Lung Cancer Study Group trial in 1995 established lobectomy as the minimum intervention necessary for the management of early-stage non-small cell lung cancer, as it was associated with lower recurrence and metastasis rates than sublobar resection and lower postoperative morbidity and mortality than pneumonectomy. There is a growing tendency to perform sublobar resection in selected cases, as, depending on factors such as tumor size, histologic subtype, lymph node involvement, and resection margins, it can produce similar oncological results to lobectomy. Alternative treatments such as stereotactic body radiotherapy and radiofrequency ablation can also produce good outcomes in inoperable patients or patients who refuse surgery.
ABSTRACT
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