Phase 1/2 trial of single-session stereotactic body radiotherapy for previously unirradiated spinal metastases.

Background: In this phase 1/2 study, the authors tested the hypothesis that single-fraction stereotactic body radiotherapy (SBRT) for previously unirradiated spinal metastases is a safe, feasible, and efficacious treatment approach.

Methods: All patients were evaluated by a multidisciplinary team. Spinal magnetic resonance imaging studies were obtained before treatment and at regular intervals to define both target volume and response to treatment.

Microsatellite instability in saliva from patients with hereditary non-polyposis colon cancer and siblings carrying germline mismatch repair gene mutations.

Microsatellites are short tandem repeats of deoxyribonucleic acid (DNA) sequences which are distributed throughout the genome. Tumors in patients with Lynch syndrome tend to accumulate mutations in microsatellites at a much higher rate than other sequences in the genome resulting in microsatellite instability (MSI). This is due to germline mutations in mismatch repair (MMR) genes.

Microsatellite instability in the peripheral blood leukocytes of HNPCC patients.

Most hereditary nonpolyposis colorectal cancer (HNPCC) patients inherit a defective allele of a mismatch repair (MMR) gene, usually MLH1 or MSH2, resulting in high levels of microsatellite instability (MSI-H) in the tumors. Presence of MSI in the normal tissues of mutation carriers has been controversial. Here we directly compare MSI in the peripheral blood leukocyte (PBL) DNA of seven HNPCC patients carrying different types of pathogenic MMR mutations in MLH1 and MSH2 genes with the PBL DNA of normal age-matched controls and of patients with sporadic colorectal cancer (SCRC).

Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of failure.

Object: The authors report data concerning the safety, effectiveness, and patterns of failure obtained in a Phase I/II study of stereotactic body radiotherapy (SBRT) for spinal metastatic tumors.

Methods: Sixty-three cancer patients underwent near-simultaneous computed tomography-guided SBRT. Spinal magnetic resonance imaging was conducted at baseline and at each follow-up visit.

Generation or birth cohort effect on cancer risk in Li-Fraumeni syndrome.

Genetic anticipation is the increased incidence, earlier onset, or increased severity of a disease in successive generations. Before the biological basis of anticipation had been demonstrated, the phenomenon was thought to be due to sampling bias, epigenetic effects, gene conversion, or recombinant events. Since then, the biologic basis for anticipation in a number of neurodegenerative disorders has been shown to be attributable to trinucleotide repeat instability, with expansion of repeats clearly correlated with an earlier age of onset.

Microsatellite instability (MSI) increases with age in normal somatic cells.

Small pool PCR (SP-PCR) is a sensitive method for the detection and quantification of microsatellite instability (MSI) in somatic cells. Here we propose that mutant microsatellite fragments accumulate with age in normal somatic cells and that this increase in MSI can be quantified by SP-PCR. MSI at 6 microsatellite loci was determined by SP-PCR in PBL DNA from 17 "normal" blood bank donors.

Phase I clinical evaluation of near-simultaneous computed tomographic image-guided stereotactic body radiotherapy for spinal metastases.

Purpose: To evaluate in a Phase I study the safety, feasibility, and patient-positioning accuracy of treating patients with intensity-modulated, near-simultaneous, computed tomographic (CT) image-guided stereotactic body radiotherapy (SBRT).

Patients And Methods: Fifteen consecutive patients with metastatic spinal disease who met protocol eligibility criteria were entered into a Phase I clinical trial. Each patient received five treatments of intensity-modulated, near-simultaneous CT image-guided SBRT, for a total of 75 treatments with 90 isocenter setups during the course of the study.

Estimating mutant microsatellite allele frequencies in somatic cells by small-pool PCR.

Identifying microsatellite instability (MSI) by partitioning DNA into multiple small pools containing only single genome amounts of DNA results in trapping both progenitor and low-frequency mutant alleles into pools where they can be identified and counted following PCR. Statistical approaches determining both the frequencies and the significant differences between frequencies of these Poisson-distributed alleles are presented. Results indicate a level of sensitivity and quantification not possible by standard PCR methods.

Power calculations for the transmission/disequilibrium and affected sib pair tests using elementary probability methods.

The transmission/disequilibrium test (TDT) and the affected sib pair test (ASP) both test for the association of a marker allele with some conditions. Here, we present methods for calculating the probability of detecting the association (power) for a study examining a fixed number of families for suitability for the study and for calculating the number of such families to be examined. Both calculations use a genetic model for the association.