J. Robert Stewart

Radiation injury to the heart

For the RTOG Consensus Conference on Late Effects of Cancer Treatment we summarize the clinical manifestations of cardiac complications appearing months to years following incidental irradiation of the heart during treatment of thoracic neoplasms. The most common effects present as pericardial disease, however, it is becoming more clear that precocious or accelerated coronary artery disease is an important late effect, especially in patients treated with radiation before the age of 21 years. To the extent it is known, the pathophysiology of the various syndromes is described and the extensive literature on dose, volume, and fractionation factors is reviewed. Based upon our current understanding of late cardiac effects, a clinical grading system has been developed and is published elsewhere in this issue.

RADIATION-INDUCED HEART DISEASE. A STUDY OF TWENTY-FIVE PATIENTS.

That high doses of x irradiation can damage the heart and pericardium is common knowledge among radiotherapists and radiobiologists. A small number of case reports have described cardiac lesions following radiotherapy of thoracic cancer; the prevailing feeling, however, is that such complications are rare and relatively unimportant (1). The purpose of this report is to review 25 cases in which significant heart disease followed radiation therapy to the chest for a variety of malignant tumors. Study of this unique series of patients from a single institution has provided data on the relative frequency of the various clinical features encountered and their correlation with the radiation technics and doses used, as well as estimates of the incidence of this group of complications in an irradiated population. The importance of recognizing cardiac complications and differentiating them from the manifestations of advancing neoplasm is emphasized. A previous report (2) described in detail the clinical findings, ...

Dose response in human and experimental radiation-induced heart disease. Application of the nominal standard dose (NSD) concept.

Abstract The application of the nominal standard dose (NSD) concept to radiation schedules in Hodgkins disease and in breast carcinoma following mastectomy has proved useful in defining “pericardial tolerance” as 1,500 rets in large-volume treatments and 1,850 rets in small-volume treatments. The dose response curve for pericardial fibrosis is similar in shape for humans and rabbits. If the heart must be included, reirradiation to tumoricidal doses for recurrence of Hodgkins disease in the thorax carries an exceedingly high risk of subsequent pericarditis or pancarditis.

Regional hyperthermia in the treatment of clinically advanced, deep seated malignancy: Results of a pilot study employing an annular array applicator

From October 1980 through December 1982, 46 patients were entered into a pilot study at the University of Utah Medical Center to assess the feasibility and safety of heating deep-seated, advanced, pelvic and abdominal malignancies with an annular array of electromagnetic wave (EMW) applicators. The patients, most of whom were heavily pretreated, were treated on a protocol in which most of the patients received combined hyperthermia and low dose X ray therapy. Discomforting local symptoms were the predominant treatment related acute side effects in 28 patients with pelvic disease, while systemic hyperthermia and associated symptoms were the predominant side effects in 18 patients with abdominal disease. Minor subacute toxicity was minimal and no serious treatment related, chronic toxicity was observed. The treatments of 22 patients with sufficiently detailed thermometry were analyzed at arbitrary index temperatures of 41 degrees C and 43 degrees C. Objective response rates in 22 evaluable patients were 67% and 9% for pelvic and abdominal sites respectively.

Regional Hyperthermia with an Annular Phased Array in the Experimental Treatment of Cancer: Report of Work in Progress with a Technical Emphasis

The annular phased aray (APA)1 has been under study at the University of Utah since late 1980. The prototype instrument was upgraded to its present configuration by April 1982. Its clinical engineering features and application are described. As of December 1982, 46 patients have been treated in a feasibility study to evaluate the use of the APA in inducing experimental regional hyperthermia for the treatment of advanced abdominal and pelvic cancer. Extensive temperature measurements from tumors and normal tissues were performed. With a few exceptions, the APA appeared capable of delivering power to deep-seated tumor volumes, but data pertaining to power distributions were scanty. Adjustment of the patient position within the aperture to achieve uniform heating is a significant problem. Treatment results are considered encouraging and there were no significant complications, but firm conclusions regarding tumor responses cannot be drawn from a study of this kind. Further studies of methods to predict power deposition patterns are needed if complications are to continue to be avoided in the more aggressive potentially curative treatments that may need to be employed in future studies.

A comparison of deep regional hyperthermia from an annular array and a concentric coil in the same patients

Twenty-two patients with advanced pelvic or abdominal malignancy (or both) were treated on successive occasions with hyperthermia produced by an annular array (AA) (60-80 MHz, 500-1800 W forward power) and a concentric coil (CC) (13.56 MHz, 350-1000 W forward power). Both devices were compared with respect to acute toxicity and power limitations. There was no power limiting factor in pelvic heating in 7/14 patients treated with the AA, however 13/14 experienced power limiting sacrococcygeal pain with the CC. The 9 patients who underwent abdominal heating had a variety of power limitations with both devices. Thermal mapping was performed in 23 treatments with the AA and in 19 with the CC. Composite thermal maps of patients with similar thermometry sites show that heating patterns produced by the CC were predictable from theory and static phantom measurements. The AA achieved broader regional heating, particularly at depth, but heating patterns were less predictable. Spatial thermal dose (TD) analysis revealed higher minimum tumor TDs and more favorable mean tumor/normal tissue TD ratios with the AA than with the CC. We conclude that the AA is superior to the CC for pelvic treatment and that both devices have limitations in abdominal treatment.

Adriamycin Cardiomyopathy: Enhanced Cardiac Damage in Rabbits with Combined Drug and Cardiac Irradiation

Rabbits received either (a) no treatment; (b) a single radiation dose; (c) protracted low-dose Adriamycin; (d) combined cardiac irradiation and low-dose Adriamycin; or (e) protracted high-dose Adriamycin. More severe myocardial lesions (similar to those in high-dose Adriamycin groups) developed in rabbits receiving combined treatment. Pericardial effusions and fibrosis were more common in the combined treatment group.

Phase I evaluation of hyperthermia equipment– University of Utah Institutional Report

At the University of Utah Medical Center the thrusts of the effort with respect to the NCl Hyperthermia Equipment Evaluation Contract have been threefold. The first objective was the development of a reliable thermometry system for collecting temperature information as a function of space as well as time. The second objective was the evaluation and comparison of a number of hyperthermia devices, particularly with respect to deep-heating devices, and specifically as pertains to the BSD annular phased array system (AA) and its various configurations. The third objective was to develop methodology for analysing hyperthermia data which could be easily adapted toward device comparison. In the period from 10/81-1/86, a total of 137 patients were treated with one or more of 10 devices, totalling 199 device evaluations at the University of Utah Medical Center or the subcontracting institution, LDS Hospital. Of these, 132 device evaluations involved deep-seated tumours. The AA was found to be feasible for deep pelvic regional hyperthermia, although the frequency of reversible acute toxicity was high, and achievement of desired temperatures was frequently limited by one of several factors. The radiative electromagnetic wave applicators which were evaluated for treatment of superficial tumours were found to be mostly feasible for tumours of the thoracic and extremities regions, although the heating patterns were frequently too shallow or too small in area, when compared with the size of the lesion.

Electron arc therapy: Physical measurement and treatment planning techniques

An electron beam arc therapy technique has been developed for the treatment of the post-mastectomy chest wall using a clinical linear accelerator modified for arc therapy. The effects on the dose distribution of primary X ray collimators, secondary cerrobend blocks attached to the accelerator accessory tray, and tertiary cerrobend casting of the treatment area on the patients thorax have been investigated. Multiple electron energies within the same arc, variable rad per degree, and variable shaped secondary and tertiary applicators have been employed to optimize dose uniformity across the treated surface. A computerized treatment planning program has been developed to aid in visualization and optimization of dose distributions. A simple technique to estimate the width variation in the secondary collimator necessary to compensate for radial patient thickness changes in the cephalocaudad direction is described. Electron beam energies of 6 MeV, 9 MeV, 12 MeV, 15 MeV, and 18 MeV have been studied. The physical measurements needed to implement this technique are described, and a comparison of electron arc therapy dose distributions with other standard treatment techniques is presented.

Hyperthermia in the treatment of cancer: Perspectives on its promise and its problems

The potential for the use of hyperthermia in the treatment of cancer is based on a strong and compelling biologic rationale. In the laboratory it has been shown in quantitative assays both in vitro and in vivo that (1) hyperthermia is cytotoxic to tumor cells as a function of time at temperatures above 42°C; (2) cytotoxicity is relatively high for radioresistant S‐phase cells and for cells that are nutritionally deprived and acidotic, conditions one might expect in regions of tumors containing large numbers of radioresistant hypoxic cells; and (3) heat is a radiosensitizer and a chemosensitizer. Clinical study is hampered by less than optimal physical heating methods and the need for invasive thermometry. Ultrasonic and electromagnetic approaches each have limitations and advantages. In spite of technical limitations, efficacy has been shown for superficial tumor sites treated by local hyperthermia and Phase I studies are underway investigating the more complicated problem of deep regional hyperthermia. Although whole body hyperthermia has the attractive capability of treating metastatic as well as more localized cancer, it is toxic therapy and its role in treatment remains undefined. Research advances in equipment design and treatment optimization are needed; however, there are studies underway utilizing existing methods and rationale which should further clarify the potential clinical usefulness of regional hyperthermia in combined modality approaches to cancer therapy.