Survival benefit of stereotactic radiosurgery for metastatic brain tumors in patients with controlled primary lesions and no other distant metastases.

The prognosis of patients with metastatic brain tumors has been very poor so far because most patients with metastatic brain tumors had other metastatic lesions and/or active primary lesions. Moreover, if no active lesions existed, local control of conventional radiation therapy was not so good, which also led to the poor prognosis. Thus, we conducted the current study concerning whether survival benefit existed in patients with controlled primary lesions and no other distant metastases, who were treated with stereotactic radiosurgery (SRS), a superior method for local control, for metastatic brain tumors. Seventy-seven patients with 90 metastatic brain tumors were treated with SRS between August 1999 and August 2001, at Tokyo Metropolitan Komagome Hospital, Japan. Of these, 10 patients with 17 metastatic brain tumors had primary lesions controlled and no other distant metastases were included in the current study. The median prescribed isocenter dose was 30 Gy (30-45 Gy) and the median prescribed peripheral dose was 25 Gy (12-30 Gy). One-year and 3-year local control rates were 90.0% and 90.0%, respectively. One-year and 3-year overall survival rates were 88.9% and 51.9%, respectively. These results suggest that SRS for metastatic brain tumors does have a survival benefit in patients with controlled primary lesions and no other distant metastases, which means that we should not treat these patients with palliative intent but pursue longer survival.

Head-to-head juxtaposition of Fas-associated phosphatase-1 (FAP-1) and c-Jun NH2-terminal kinase 3 (JNK3) genes: genomic structure and seven polymorphisms of the FAP-1 gene.

When characterizing the 5' flanking region of the c-Jun NH2-terminal kinase 3 ( JNK3) gene at 4q21-22, where frequent allelic losses and loss of expression had been detected in patients with brain tumors and hepatocellular carcinomas, we discovered that the Fas-associated phosphatase-1 ( FAP-1) gene was located only 633 bp upstream from JNK3 in a head-to-head orientation. A short G/C-rich region between the cap sites of the two genes suggested that they might share a bidirectional promoter region that appeared to contain multiple cis elements, including Sp1, AP-1, AP-2, GATA-1, a GC box, and a CCAAT box. The FAP-1 gene, consisting of 48 exons, initiates transcription within exon 2 and terminates in exon 48. Exons 2-5, 21-23, 25-28, 29-30, 33-34, and 34-36 encode six Gly-Leu-Gly-Phe repeat domains, and exons 12-17 and 44-88 encode the membrane-binding and catalytic domains, respectively. Seven polymorphisms were identified within functional domains or the putative promoter region, including two with amino acid substitutions, Leu1419Pro and Ile1522Met.