High PCNA index in meningiomas resistant to radiation therapy.

PURPOSE: Meningiomas are common intracranial tumors, often well controlled with surgical resection alone. While the efficacy of radiation therapy in improving local control and progression-free survival is well documented, prognostic data substantiate factors that are predictive of poor local control following definitive radiation therapy. PCNA is a DNA polymerase expressed at the highest levels in the S-phase, the most resistant portion of the cell cycle to ionizing radiation in vitro. We investigated the possible correlation between the levels of PCNA expression and the clinical outcome of patients treated with definitive radiation therapy. METHODS AND MATERIALS: Archival tissue was collected from 33 cases of meningioma treated at our institution for definitive radiation therapy between 1970 and 1990. Age-matched normal meningeal tissue and asymptomatic meningiomas removed at autopsy served as tissue controls. A standard ABC immumoperoxidase technique employing antibodies to PCNA, PC-10 (Dako, California) was used to stain specimen slides for PCNA. PCNA index was defined as the number of positive nuclei per 10 high-power fields at 400x magnification. Two independent observers scored the slides without prior knowledge of the cases at hand. RESULTS: Patients with high PCNA index were less likely to be controlled by therapeutic radiation (p < 0.001, Kaplan-Meier). All patients with a PCNA index greater that 25 failed radiation therapy. Using multivariate analyses, malignant (but not atypical), histology and PCNA index were significant predictors of progression following radiation therapy (p < 0.05, log rank). CONCLUSION: PCNA index may be a useful adjunct to more standard histopathologic criteria in the determination of meningioma local control and progression-free survival following therapeutic irradiation. Data on a more expanded population evaluated on a prospective basis will be needed before such criteria are routinely employed in the clinical setting.

Opportunities with combined modality therapy for selective organ preservation in muscle-invasive bladder cancer.

Combined-modality therapy for organ preservation represents an appropriate alternative to radical surgery in the management of several malignant diseases. The standard therapy for muscle-invasive bladder cancer in the United States has been radical cystectomy. Although the sequelae of radical surgery have been ameliorated somewhat by techniques for the construction of orthotopic bladders, the ideal therapy should both cure the patient of cancer and maintain a functioning natural bladder. Years of experience in Europe and Canada with bladder preservation using radiation therapy are documented. Advances in transurethral surgery technique and in the combination of radiation and chemotherapy have led to safe and effective regimens for patients with bladder cancer. Several recent trials with combined-modality therapy have established this treatment as a viable alternative to radical cystectomy in selected patients.

Bilateral breast carcinoma after radiation therapy for Hodgkin's disease.

The success of modern cancer therapy is resulting in an increasing number of long-term cures. The price of success, however, is the incidence of treatment-related morbidity and mortality. The physician should be aware of the potential sequelae of cancer therapy. A case of bilateral breast cancer occurring 13 years after radiation therapy for Hodgkin's disease prompted me to examine the incidence of this problem and to make recommendations for surveillance of patients.