Survival After Stereotactic Body Radiation Therapy for Clinically Diagnosed or Biopsy-Proven Early-Stage NSCLC: A Systematic Review and Meta-Analysis.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is a promising curative treatment for early-stage NSCLC. It is unclear if survival outcomes for SBRT are influenced by a lack of pathological confirmation of malignancy and staging of disease in these patients. In this systematic review and meta-analysis, we assess survival outcomes after SBRT in studies with patients with clinically diagnosed versus biopsy-proven early-stage NSCLC. METHODS: The main databases were searched for trials and cohort studies without restrictions to publication status or language. Two independent researchers performed the screening and selection of eligible studies. Outcomes were overall survival, cancer-specific survival, and disease-free survival. The inverse variance method and the random effects method for meta-analysis were used to assess pooled survival estimates. RESULTS: A total of 11,195 nonduplicate records were identified by the original search strategy. After screening by title and abstract, 1051 potentially eligible records were identified. A total of 43 articles were included. The comparative studies showed lower 3-year overall survival and lower 2-year and 5-year cancer-specific survival for biopsy-proven disease compared to clinical disease. However, 5-year overall survival was the same for both groups. For the pooled estimates, 3-year disease-free survival and 2-year cancer-specific survival were lower for biopsied disease. CONCLUSIONS: Results of this systematic review and meta-analysis show a discrepancy in oncological outcomes for patients undergoing SBRT for suspected early-stage NSCLC in whom there is pathologic conformation of malignancy and those who there is only a clinical diagnose of NSCLC. These results emphasize the importance of obtaining pathologic proof of malignancy.

Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.

We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.

Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer.

We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 x 10(-12) for rs10941679). The nearest gene, MRPS30, was previously implicated in apoptosis, ER-positive tumors and favorable prognosis. A recently reported signal in FGFR2 was also found to associate specifically with ER-positive breast cancer.