An automated method for adaptive radiation therapy for prostate cancer patients using continuous fiducial-based tracking.

Electromagnetic tracking technology is primarily used for continuous prostate localization during radiotherapy, but offers potential value for evaluation of dosimetric coverage and adequacy of treatment for dynamic targets. We developed a highly automated method for daily computation of cumulative dosimetric effects of intra- and inter-fraction target motion for prostate cancer patients using fiducial-based electromagnetic tracking. A computer program utilizing real-time tracking data was written to (1) prospectively determine appropriate rotational/translational motion limits for patients treated with continuous isocenter localization; (2) retrospectively analyze dosimetric target coverage after daily treatment, and (3) visualize three-dimensional rotations and translations of the prostate with respect to the planned target volume and dose matrix. We present phantom testing and a patient case to validate and demonstrate the utility of this application. Gamma analysis of planar dose computed by our application demonstrated accuracy within 1%/1 mm. Dose computation of a patient treatment revealed high variation in minimum dose to the prostate (D(min)) over 40 fractions and a drop in the D(min) of approximately 8% between a 5 mm and a 3 mm PTV margin plan. The infrastructure has been created for patient-specific treatment evaluation using continuous tracking data. This application can be used to increase confidence in treatment delivery to targets influenced by motion.

Absence of correlation between telomerase activity and hepatic neoplasia in B6C3F1 mice.

Telomeres are the physical ends of eukaryotic chromosomes, which maintain chromosome stability and are progressively shortened with aging in somatic cells. The enzyme telomerase elongates telometric DNA and while not usually detectable in human somatic cells is expressed in most human tumors. The present study was conducted to determine if telomerase activity is a marker for spontaneous hepatic neoplastic changes in B6C3F1 mice, a strain frequently used in rodent carcinogenicity studies. Telomerase activity was generally higher in microscopically normal liver tissue from 8-week-old compared to aged mice (110-week-old); however, telomerase activity was not consistently increased in hepatocellular adenomas and carcinomas. It is proposed that, while elevated telomerase activity may modulate human tumor development, modulation of telomerase activity is not a feature of hepatic tumors in B6C3F1 mice and therefore is unlikely to have utility as a molecular marker for hepatic neoplasia in this mouse strain.

Hepatotumorigenicity and peroxisome proliferation induced by the hypolipidemic CI-924 in a two-year study in male and female B6C3F1 mice.

The hepatic tumorigenicity of CI-924 (5,5'-(1,1'-biphenyl)-2,5-diylbis(oxy)(2,2-dimethylpentanoic acid)), a hypolipidemic agent, was evaluated in 50 B6C3F1 mice/sex/dose given drug in the diet at 0, 5, 25, and 75 mg/kg/day for 2 yr. Peroxisomal and drugmetabolizing enzyme determinations, as well as ultrastructural evaluations, were conducted in subsets of these same groups, because drugs of this class cause peroxisome proliferation and hepatic tumors in rodents. CI-924 elicited dose-dependent increases in the incidence of hepatocellular adenomas and carcinomas in both sexes that were statistically significant at 75 mg/kg. Stereologic evaluation revealed significant increases in hepatocellular peroxisome volume ratio, due to increased numbers of peroxisomes, in females at all doses and males at 75 mg/kg. Peroxisomal enzyme activity measurements revealed no change in catalase, but dose-dependent increases in carnitine acetyltransferase and cyanide-insensitive beta-oxidation in both sexes. Peroxisome proliferation, determined biochemically or ultrastructurally, was twice as great in females compared to males. Total cytochrome P-450 was increased in both sexes given 75 mg/kg. There were dose-dependent decreases in glutathione S-transferase in males and increased glutathione peroxidase in both sexes at 25 and 75 mg/kg. In conclusion, this study demonstrated that while CI-924 induced hepatic tumors in male and female B6C3F1 mice the associated peroxisome proliferation, while moderate in females, was only weak in the males after 2 yr of exposure.

EDTA separation and ATPase Langerhans cell staining in the mouse epidermis.

Sheets of ethylenediaminetetraacetic acid (EDTA)-separated epidermis were examined using scanning electron, transmission electron, and light microscopy; sheets were also examined after staining for adenosine triphosphatase (ATPase) activity. Staining was improved by longer incubation with EDTA and by elimination of Trismal buffer as a tissue rinse. EDTA-separated epidermis showed better retention of ultrastructural integrity when washed with phosphate-buffered saline. The ATPase staining procedures described in this present study are ultrastructurally specific for the Langerhans cell.

The Langerhans cell in hairless mouse epidermis.

Hairless mouse epidermis was separated from the underlying dermis using a 2 h incubation in 20 mM ethylenediaminetetraacetic acid (EDTA). The basal epidermis, thus exposed, was then examined using scanning electron (SEM), transmission electron (TEM), and light microscopy (LM). Sheets were also stained for: (i) Langerhans cell adenosine triphosphatase (ATPase), beta-glucuronidase, and la antigens; and, (ii) melanocyte 3,4-dihydroxyphenylalanine (DOPA)-oxidase. A regular distribution of protruding dendritic cells was observed superficial to the basal epidermis. These external dendritic cells were identified as Langerhans cells on the basis of subcellular morphology and distribution in the TEM. ATPase staining was Langerhans cell specific. The Langerhans cell population in hairless mouse epidermis was large, and evenly distributed in the interfollicular epidermis and the outer root sheath of degenerate hair follicles. The melanocyte population, in comparison, was negligibly small (4-5 cells per mm2).

Benign breast lesions and subsequent breast carcinoma in Rochester, Minnesota.

Case histories of 444 female patients (Rochester residents) with benign breast disease pathologically diagnosed between 1935 and 1949 were studied prospectively for the development of breast cancer. After exclusion of unsuitable cases, 370 remained for review of pathologic diagnoses and statistical analysis. Breast cancer developed in 14 (3.8%) within a median period of 13.5 years after the diagnosis of benign breast disease. Most of these malignancies occurred within 10 years after the original diagnosis. Patients in whom the original diagnosis was chronic cystic mastitis developed breast cancer 2.9 times more frequently than expected. Breast cancer developed 10 times as often as expected in those patients of ages 40 to 49 at the time of diagnosis of breast malignancy. This evidence shows that a more intensive follow-up of patients with confirmed chronic cystic breast disease is justified, especially among those of ages 30 to 49 years.