Stereotactic radiosurgery for metastatic spine tumors.

Spinal metastases invariably affect the majority of patients with cancer. Many will develop symptoms related to pain and disability from epidural spinal cord compression as well as pathologic fracture of the vertebrae. With the emergence of targeted systemic therapies and a better understanding of cancer biology, patients are living longer with bony metastases. This poses particular challenges, as palliation of pain and maintenance of local tumor control are paramount to quality of life and overall functional independence for these patients. Stereotactic radiosurgery (SRS) has emerged as a potent primary standalone and adjuvant treatment option for spinal metastases. To date, the primary indications for SRS include 1) upfront standalone treatment for painful bony metastases in the oligometastatic patient, 2) standalone or post-operative treatment following progression or recurrence of local disease despite previous conventional external beam radiation therapy (cEBRT), and 3) following surgery during which epidural disease is decompressed and the spine stabilized when indicated. SRS has demonstrated a significant advantage over cEBRT for tumors traditionally regarded as relatively radioresistant such as sarcoma, melanoma, renal cell carcinoma, non-small cell lung cancer and colon carcinoma.9 The radiobiological advantage of increased tumoricidal dose delivery and spinal cord dose sparing in SRS have made this a powerful treatment alternative to cEBRT particularly within the context of re-irradiation. Given the limitations of spinal cord dose constraints, surgery is still the first-line therapy in patients with high-grade epidural spinal cord compression (ESCC). Epidural compression can be treated with SRS, however this risks radiation-induced myelopathy and challenges the safety of effective dose delivery at the dural margin.11 With increasing dose, radiation-induced vertebral fracture is the most serious and prevalent side effect of SRS.53 An overview of SRS, including the most common indications, complications, and outcomes for spinal metastases are presented here.

Four SNPS on chromosome 9p21 confer risk to premature, familial CAD and MI in an American Caucasian population (GeneQuest).

Genome-wide association studies have separately identified four single nucleotide polymorphisms (SNPs) on chromosome 9p21 that confer susceptibility to coronary artery disease (CAD) and myocardial infarction (MI). This study presents the first analysis of these SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) in a premature, familial CAD/MI population (GeneQuest). We performed a case-control analysis of the GeneQuest Caucasian population with 310 cases with premature CAD and MI (average age at onset of 40.3 +/- 5.1) and 560 non-CAD controls to determine if these SNPs are associated with risk of CAD using both the population-based and family-based association study designs. The four SNPs are significantly associated with premature and familial MI and CAD in the GeneQuest Caucasian population (allelic P= 6.61 x 10(-7) to 1.87 x 10(-8)). Sib-TDT analysis showed that three of the four SNPs could confer significant susceptibility to premature CAD and MI. These results indicate that the four SNPs on chromosome 9p21 are also associated with premature, familial CAD.