Lawrence W. Margolis

Modification of radiation injury to normal tissues by chemotherapeutic agents

The effects of several cancer chemotherapeutic agents on radiation damage to normal intestine, esophagus, and lung tissue were evaluated in LAF1 mice using quantitive endpoints. In all tissues tested, actinomycin D increased injury and BCNU did not. In the intestine, adriamycin enhanced radiation damage more than any other agent. Bleomycin increased damage in the esophagus but not in the lung or intestine. Cyclophosphamide increased injury only in the lung, where vincristine caused minimal injury, and hydroxyurea, none. Only prednisolone caused significant radioprotection when given at the time of irradiation or at the time of expected death from pulmonary injury.

Radiation pneumonitis: A new approach to the derivation of time‐dose factors

A series of 51 patients treated with 92 separate lung fields for metastatic pulmonary disease between 1958 and 1971 is reviewed. The treatment data are converted into nominal single doses (NSD) and a newly derived formula for estimated single doses (ED). The 5% incidence level of pneumonitis without dactinomycin is 770 rets (NSD) and 510 rets (ED) and with dactinomycin, 520 rets (NSD) and 450 rets (ED). A safe treatment regimen for avoiding radiation pneumonitis is 1500 rads in 10 fractions with dactinomycin and 2500 rads in 20 fractions without dactinomycin.

The role of radiation therapy in the management of ocular reticulum cell sarcoma.

Nine patients with ocular lymphomas were seen in the Department of Ophthalmology and the Division of Radiation Oncology at UCSF and Ralph K. Davies Medical Center, San Francisco, from 1978 through 1974. Six of the 9 patients had visual symptoms as the first manifestation of their disease. Eight of the 9 patients developed intracranial lymphoma at some time during the course of the disease. Despite lymphoma work‐up including bone marrow biopsies and lymphangiogram, only 1 patient was found to have documented systemic involvement. The diagnosis of ocular lymphoma was based on pathologic material from the eye in 5 cases or from central nervous system biopsy in 4 patients in association with tumor cell infiltrates in the retina and vitreous clouding. Radiation therapy to the eyes improved vision in 10 of 13 eyes treated in 8 patients. The usual dose was in the range of 3500 to 4500 rads given over 4–5 weeks. In addition, 7 patients received central nervous system irradiation. Review of the literature reinforced the findings of this series showing the frequent association of ocular lymphoma with intracranial lymphoma and the rare systemic dissemination. This disease process has previously been referred to as ocular reticulum cell sarcoma. Cancer 45:688‐692, 1980.

Complications of Cobalt Plaque Therapy of Choroidal Melanomas

We treated a small series of patients with choroidal malanomas with radioactive cobalt plaques. To assess the effectiveness of radiation, we performed radioactive phosphorus (32P) uptake determinations before and after treatment. The 32P results did not tumor destruction. In five of seven patients with posterior pole melanomas, radiation retinopathy developed after treatment with resultant decrease in vision.

Radiotherapy for High Grade Clinically Localized Adenocarcinoma of the Prostate

PURPOSE We defined the efficacy of radiotherapy for the treatment of high grade (Gleason scores 8 to 10) adenocarcinoma of the prostate. MATERIALS AND METHODS A total of 50 patients underwent radiotherapy with curative intent for clinically localized prostate cancer with Gleason scores of 8 to 10 at 1 of 4 facilities affiliated with the University of California San Francisco. Patients were considered to have biochemical failure if they had a significant increase in prostate specific antigen (PSA) of 0.5 ng./ml. per year, an increase in PSA to greater than 1.0 ng./ml. or a positive biopsy. RESULTS Among the 50 patients median PSA was 22.7 ng./ml. (range 1.3 to 93.4). Tumors were clinical stage T1 or T2 in 46% of the cases and stage T3 or T4 in 54%. The overall actuarial probability of freedom from biochemical failure at 4 years was 23%. In a multivariate analysis including all patients pretreatment PSA was the only predictor of PSA failure, with 64% free of progression if the pretreatment PSA was 10 ng./ml. or less compared to only 16% at 3 years if PSA was more than 10 ng./ml. (p = 0.01). In a multivariate analysis restricted to patients with PSA less than 20 ng./ml. 83% of those treated to more than 71 Gy. were free of progression compared to 0% for those treated to less than 71 Gy. (p = 0.03). In a multivariate analysis PSA 10 ng./ml. or less (related risk 11.4, p = 0.02), T stage 1 or 2 (relative risk 3.8, p = 0.05) and radiation dose more than 71 Gy. (relative risk 4.0, p = 0.06) were associated with a favorable outcome. CONCLUSIONS At 4 years the freedom from PSA failure following radiotherapy for high grade prostate cancer was comparable to previously reported surgical series. The high failure rate among patients with PSA greater than 20 ng./ml. suggests that these patients should be considered for investigational approaches. The apparent improvement in freedom from progression with the use of higher doses provides reason for optimism.

Ocular Reticulum Cell Sarcoma

Three patients with ocular reticulum cell sarcoma underwent treatment with a combination of chemotherapy and irradiation. All three patients have survived an average of 36 months after treatment, significantly longer than would have been expected with radiation therapy alone. The chemotherapy appears to arrest the progression of central nervous system disease that eventually kills most patients with ocular reticulum cell sarcoma.

Whole-Lung Irradiation for Metastatic Tumor

In The Treatment of metastatic disease of the lung, the injury to the lung parenchyma from irradiation must be weighed against the possibility of long-term control. A clinical picture of radiation injury to the lung was first described by Groover et al. in 1922 (7). Symptoms usually begin one to three months after a protracted course of radiation therapy, but may be delayed as long as six months (16). The acute reaction may subside leaving no clinical or roentogenographic residua, or it may progress to an irreversible fibrosis (2, 17, 18, 20). Variables known to influence the development of radiation pneumonitis include the dose of radiation, the plan of fractionation, the volume of lung treated, infection, and modifying drugs (5,8, 11, 13, 16). In this study these factors are correlated with the development of radiation pneumonitis and with control of the tumor after whole-lung irradiation for metastatic tumors. Material And Method This series consists of 25 patients treated at the University of Californ...

Intramedullary tumor metastasis simulating radiation myelitis: Report of a case

A case of suspected radiation myelitis based on clinical history, previous irradiation, neurologic deficit in the irradiated volume, and normal myelogram is reported. At autopsy, intramedullary metastatic disease was found, but no radiation damage. All radiation details must be considered before making the diagnosis of radiation myelitis with confidence. It is important not to exclude other potentially helpful treatment, such as surgery or chemotherapy, by the presumptive diagnosis of radiation myelitis.

Treatment of Metastatic Wilms's Tumor

Whole lung irradiation (1,500 rads in 10 fractions) was combined with dactinomycin in the treatment of 17 children with metastatic Wilmss tumor. Seven patients (54%) remained disease-free for at least two years. In addition, liver metastases developed in 2 of these survivors who were effectively treated with surgery, irradiation, and chemotherapy. Our control rate is similar to rates found in the literature, which demonstrates that an aggressive treatment approach for patients with metastatic disease by a multidisciplinary pediatric oncology group is worthwhile.

Partial hepatectomy in metastatic Wilms' tumor

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