Richard J. Carella

The palliation of brain metastases in a favorable patient population: a randomized clinical trial by the Radiation Therapy Oncology Group.

Abstract The palliative effectiveness of a short, intensive course of brain irradiation (3000 rad in 2 weeks) was compared to that of a high-dose course (5000 rad in 4 weeks) in a randomized RTOG clinical trial. Eighty percent of the 255 evaluable patients had lung primaries, 7% breast, and 13% other or unknown primaries. Patients with evidence of extra-cranial metastases, uncontrolled primaries, or Class IV Neurologic Function (NFIV) were excluded. Forty-one percent of NFII and 71 % of NFIV patients improved in neurologic function class. For NFII patients, a significantly greater improvement rate was obtained with the short course than with the long course. Otherwise there were no significant differences between the two regimens with respect to palliation of symptoms, improvement rate, median time to progression, cause of death, or median survival. We conclude that 3000 rad in two weeks is at least as effective as 5000 rad in four weeks in the palliation of brain metastases, even in this relatively favorable patient population.

Role of radiation therapy in the management of meningioma.

Surgery is the accepted form of treatment of meningioma; the role of radiotherapy has not been clearly established. With this in mind, we have reviewed our experience with radiation therapy in the management of meningiomas at New York University Medical Center. Sixty-eight patients fell into three groups. Forty-three (Group A) underwent operation followed by radiation therapy, 14 patients (Group B) had radiation for recurrence after operation, and 11 patients (Group C) had radiation therapy as the primary treatment. In Group A, 41 of 43 are alive. During a follow-up of 1 to 10 years, only 2 have deteriorated. Five of 14 Group B patients showed neurological improvement and 7 showed deterioration, including 5 who died of tumor. All 11 patients in Group C are alive with follow-up periods of 3 to 6 years; 9 of these show improvement in neurological function. Eleven patients had malignant meningioma, of whom 8 are alive and stable. We present 4 case reports, including computed tomographic scans that show evidence of tumor necrosis after radiation therapy. Pathological verification of tumor necrosis is presented in 1 case. We believe that radiation therapy has an established role in the treatment of incompletely excised, recurrent, or malignant meningiomas and, in some cases, as the initial management of meningiomas. Indications for treatment and guidelines are presented.

Value of radiation therapy in the management of patients with cerebral metastases from malignant melanoma: Radiation Therapy Oncology Group Brain Metastases Study I and II.

Sixty patients from two Radiation Therapy Oncology Group (RTOG) studies with cerebral metastases from malignant melanoma were analyzed to determine the response to whole brain irradiation. General performance status, neurologic function, and specific neurologic symptoms were evaluated for rate and duration of improvement. Also analyzed was the influence of chemotherapy and steroids, although neither was a controlled factor. Results indicate a significant benefit from radiation therapy in terms of symptomatic and neurologic function improvement. Symptomatic improvement was observed in 76%, with 31% completely improved. Of the four most frequent symptoms, complete or partial improvement was observed as follows: headache—27 of 37 patients (73%); motor loss—14 of 23 patients (61%); impaired mentation—13 of 24 patients (62%); and convulsions—10 of 12 patients (83%). Improvement in neurologic function class was observed in 18 of 44 patients (41%). Median survival for Study 1 patients was 10 weeks (range 1–200) and that of Study II patients 14 weeks (range 1–76). These results are comparable to those found in radiation therapy of brain metastases from all other primary tumors. Cancer 45:679‐683, 1980.

The Usefulness of Computed Tomography During and After Radiation Therapy in Patients with Brain Tumors

Two years of experience with 100 patients in the serial study of brain tumors during and after radiation therapy has shown that computed tomography is useful in (a) depiction of regression or growth of primary and metastatic intracranial tumors, (b) recognition of untoward sequelae of radiation therapy, such as necrosis and edema, and (c) appreciation of changes in tumor density and ventricular size. Representation cases are discussed and illustrated.

Large fraction radiotherapy plus misonidazole for treatment of advanced lung cancer: report of a phase I/II trial.

From August 1978 through December 1979, 51 patients with advanced non-oat cell carcinoma of the lung were enrolled in a Phase I/II trial sponsored by the Radiation Therapy Oncology Group (RTOG) employing misonidazole (a 2-nitroimidazole) as a hypoxic cell sensitizer and radiation. The purpose of this study was to test drug and radiation tolerance and to assess the short term efficacy of this unconventional treatment. Tumor doses of 600 rad wer given twice weekly for three weeks for a total of 3600 rad, preceded four to six hours by misonidazole in a dose of 2 gm/m2 or 1.75 gm/m2, administered orally. Forty-nine patients were evaluable. Serious toxicity from this treatment was rare. Grade 2 or 3 peripheral neuro-toxicity occurred in eight of 24 patients (33%) with drug doses of 2 gm/m2 and in four of 26 patients (15%) who received 1.75 gm/m2. Grade 3 or 4 central nervous system toxicity occurred in two patients. Two patients developed serious late radiation complications: one patient had a transverse myelitis that appeared one year following delivery of 3600 rad to the spinal cord; a second patient developed a tracheoesophageal fistula and pericarditis eight months following treatment. Objective responses were reported in 67% of patients (complete in 18%); 70% of the patients died with a median survival time of nine months. Of 32 patients eligible for 12 month follow-up, 34% survived more than one year. Patterns of relapse after initial treatment and comparison with results from other RTOG trials using conventional fractionation are discussed.

Computerized (axial) tomography in the serial study of cerebral tumors treated by radiation. A preliminary report.

The difficulty in evaluating the effectiveness of radiation therapy of primary cerebral tumors is well appreciated. Changes in tumor size and the presence or absence of edema or necrosis during or following treatment cannot be readily evaluated by present noninterventive roentgenographic methods. At New York University Medical Center, computerized (axial) tomography (CT) has been routinely used both before and after radiation therapy with the aim of assessing, by noninterventive means, tumor response, presence or absence of edema, or necrosis. A selected series of patients is presented with correlation of the clinical findings and CT‐scan results both before and after therapy. The significance of these findings and their implications in the management of cerebral tumors are discussed.

Assessment of the irradiated brain by quantitative computerized tomography scan analysis—II. Application in studies of the necrotic and edematous braint

Abstract In this second part of a 2 part report, the authors present clinical application of the methods developed in Part I, a quantitative analysis of brain parenchyma and ventricular volume. Part II presents computerized tomography (CT) studies and histogram analyses of a patient with cerebral edema and 2 patients with autopsy proven radiation necrosis. Preliminary data from CT number frequency distributions for normal, edematous and necrotic brain suggest that while reversible and irreversible changes in brain tissue may not be separable on evaluation of brain parenchyma alone, quantitative analysis of CT numbers for cerebrospinal fluid in large numbers of patients may provide the basis for differentiating degrees of radiation damage.

Assessment of the irradiated brain by quantitative computerized tomography scan analysis—I: Sampling methods and concepts

Abstract An investigation was initiated, aimed at evaluating quantitative computerized tomography (CT) analysis of the irradiated brain in an effort to differentiate recoverable from non-recoverable damage. This segment is the first part of a 2 part preliminary report and describes the methods used in sampling and analyzing parenchyma and ventricular volume. A statistical analysis of normal patient data served to determine the 90% confidence interval for the range of CT numbers for unirradiated tissue. Data derived from 3 patients (described in detail in Part II), implies that there may be sufficient difference to detect varying degrees of injury.

Radiotherapy for bronchogenic carcinoma.

Treatment of carcinoma of the lung to cure or even to prolong survival time to a satisfactory degree is not yet a reality. For squamous cell carcinoma confined to the lung, radical surgery offers the best possibility of cure. When surgery is not feasible in such a case for other than technical reasons (eg, poor general condition of the patient), radical (megavoltage) radiotherapy offers a good possibility of cure. For anaplastic or oat cell carcinoma confined to the lung, cure by surgery or radiotherapy is less likely and there is little advantage of one or the other of these modalities. Once metastasis has occurred, surgery is largely precluded and radiotherapy becomes a measure of last resort that offers a good possibility of relief of distressing symptoms and some hope of prolonging worthwhile life.