Samuel Hellman

Improvement in Quality of Survival Following Whole-Brain Irradiation for Brain Metastasis

The benefits of palliative therapy for patients with brain metastases have often been questioned (1–4) since these patients usually have widely disseminated disease and a limited survival. Assessment of therapeutic gain or successful palliation has proved to be the most difficult task. Prolongation of life (2, 5), or “increased survival for at least six months without further disability” (3), has been the surgical criterion for success, and amelioration of signs was reported as the criterion in the largest radiotherapeutic series (6). Yet, ultimately, it is the improvement of the functional capacity of the patient, his regained intellectual awareness and physical abilities, that determines whether a palliative result has been achieved. It is the purpose of this study to review the clinical findings, results, and implications of the treatment of brain metastases in 108 patients treated with whole-brain radiation. A patient classification based on functional status, which defines improvement and reports suc...

Sequelae of Radical Radiotherapy of Carcinoma of the Lung

Although radiotherapy offers adequate palliation of symptoms in inoperable carcinoma of the lung, the overall cure rates have been disappointing (1–4). A recent study reported a high incidence of severe complications in long-term survivors of treatment (5). We were interested in the frequency of complications, both acute and late, in our patients following radical radiotherapy. This is of major importance because of the reports of Bleodorn et al. (6–8) and other workers (9, 10) concerning the possible advantage of combined radiotherapy and surgery in the management of carcinoma of the lung. If this combination therapy increases the survival rate of patients with carcinoma of the lung, more who receive radical radiotherapy will be exposed to long-term complications. Included also in this report are survival data of all patients and our preliminary observations on patients given radiation followed by surgery. Methods All 132 persons treated in our institution (Grace-New Haven Community Hospital) for primary...

Renal Hypertension Secondary to Unilateral Radiation Damage Relieved by Nephrectomy

The possibility of renal damage resulting from therapeutic irradiation was pointed out early in the history of radiation therapy (1, 2, 7, 9). The danger was largely disregarded, however, until reports of a large number of cases from Manchester emphasized the frequency of grave renal complications when the kidney received irradiation in the therapeutic dosage range (4, 6, 8). A latent period of thirteen years between irradiation and the appearance of hypertension has been recorded (5). In that instance, nephrectomy restored the blood pressure to normal. The present report describes a case of hypertension secondary to radiation-induced renal damage, detected eighteen years after x-ray treatment in which both kidneys were included in the field. Only one kidney demonstrated significant abnormality, and its removal twenty-four years after the irradiation returned the blood pressure to normal. Case Report J. B., a 64-year-old white male, was referred for treatment of an aortic aneurysm in 1963. His blood press...

Sequential chemotherapy and radiotherapy. Preliminary results of clinical trial with methotrexate in head and neck cancer.

The number of drugs which have been proved to sensitize cells to ionizing radiation is limited. Clinically, differential sensitization must be obtained in which the drug, when combined with irradiation, results in a greater effect on the tumor than on the normal tissues. No such therapeutic effect has been observed with available sensitizers. The halogenated pyrimidines, 5-bromodeoxyuridine (BUDR) (3) and 5-iododeoxyuridine (IUDR) (5), have been shown to sensitize cells grown in tissue culture to ionizing radiation. IUDR was found to markedly increase the effectiveness of ionizing radiation in patients (2, 10). In those subjects in whom relatively low-energy x rays were used, however, a marked effect was also observed on the skin. A suitable measure of the relative reaction of the skin as compared to tumor response was not available, so proof is still lacking that IUDR represents a suitable clinical radiation-sensitizer. Other drugs such as 5-fluorouracil (5-FU) are thought by some (8) to sensitize human ...

Carcinoma of the tongue and floor of the mouth results of radical radiotherapy

A review was made of 104 cases of carcinoma of the tongue and floor of the mouth treated at the Hunter Radiation Center of the Yale New Haven Hospital from October 1958 through December 1966. This study was undertaken to determine the cure rates and complications of irradiation therapy in the management of this disease. The cure rates varied according to the location and stage of the tumor. The overall, corrected, cumulative 3‐year survival was 45%. Serious complications developed in 5% of the patients. Twenty‐six patients considered to be radiation failures underwent resectional surgery. The results of this study justify continuation of the approach thus far employed. To improve the cure rates, emphasis ought to be put on earlier detection of cases.

Radiation Fractionation as Applied to Murine Colony-Forming Cells in Differing Proliferative States

DOSE INCREMENT and patterns of dose fractionation are often modified in clinical radiotherapy, depending upon the response and tolerance of the patient. Small changes in daily dose rate may result in obvious clinical differences. This is most apparent in the region of the head and neck, where the response of the mucosal tissues is easily observed. The purpose of this study is to quantitatively explore some current fractionation schemes and their modifications as applied to an in vivo system during differing proliferative states. A preliminary description of some of these data has been reported previously (3). An in vivo assay system developed by Till and McCulloch (9) was used to compare different clinical dose fractionation schemes. Mice were subjected to whole-body radiation of 500 to 900 R, and macro-scopic spleen colonies (endocolonies) were noted nine days later. Similar colonies can be formed by injecting syngeneic bone marrow intravenously into animals which have previously been irradiated sufficie...

Cell kinetics, models, and cancer treatment--some principles for the radiation oncologist.

The radiation oncologist must attempt to apply the developments in the laboratory to the clinical situation in a manner that will result in a therapeutic gain. The possible influences of radiation fractionation and protraction, cell renewal and recruitment of normal or tumor tissues, differences in acute and late radiation effects and possible chemotherapy-radiation interactions are all factors that can affect the ultimate result. In order to develop a therapeutic gain, the effect on the tumor must be greater than on the normal tissues.

STUDIES ON DOSE FRACTIONATION AS MEASURED BY ENDOGENOUS SPLEEN COLONIES IN THE MOUSE.

Dose fractionation is often modified in clinical radiotherapy, depending on the response and tolerance of the patient. Small changes in daily dose increment or brief interruption of daily treatment can make obvious clinical differences. It is the purpose of this study to explore quantitatively in an animal system some current fractionation schemes and their modifications. An in vivo assay system developed by Till and McCulloch (1) is used to compare different clinical dose-fractionation schemes. In mice subjected to 500–900 R whole-body irradiation, macroscopic spleen colonies are noted nine days later. These colonies appear to be derived from a single progenitor cell (2). By varying the dose, a survival curve for these endocolonies can be drawn and is similar to survival curves of irradiated bone marrow transplanted into lethally irradiated mice (exocolonies) (3). Endogenous spleen colonies have an advantage compared to exocolonies in that they afford a means of assessing the population in situ without t...