In the May and June, 1974, issues of PEDIATRIC ANNALS a series of excellent articles dealt with a group of malignant neoplasms, in the majority of which radiation therapy played a significant role in management. Unquestionably radiation therapy is contributing to an improved prognosis in these devastating diseases. As in the application of any modality - e.g., surgery - to the patient with cancer, the manner of application of radiation therapy determines not only the likelihood of eradication of the disease but also the likelihood of undesirable normal-tissue effects.
The article on retinoblastomas by Tapley in the June, 1974, issue (Vol. 3, No. 6) beautifully illustrates these points. Depending on the quality of radiations, the volume irradiated, the dose of radiation fractions, and the total dose delivered, the cure rate for each stage of disease varies. Likewise, the acute or near-immediate effects of radiation and the late effects of radiation are dose-related.
It is important, however, to constantly bear in mind that, particularly in pediatrie neoplasms, if the quantity of ionizing radiations can be reduced or even omitted without jeopardizing the chance of cure, this becomes the most desirable goal. While many examples of this precept are available, the following three are illustrative.
Wilms's tumor. In many medical centers in the past, pre- and postoperative radiation therapy was frequently administered to children. While the use of this technique has probably improved overall survival, the permanent effects of ionizing radiations - e.g., bone growth retardation, bowel mucosal alterations, and increased risk of carcinogenesis - are undesirable. The recent introduction of the chemotherapeutic agent vincristine in the therapeutic regimen for Wilms's tumor is a proper and judicious substitute for preoperative radiation therapy . Obviously, postnephrectomy radiation therapy for selected cases - e.g., postsurgical residual disease, local and/or nodal - is still indicated.
Neuroblastoma. This is an extremely rathosensitive disease. There is no clinical evidence that the larger the dose administered, the greater the chance of control of the local lesions. Radiation therapy should be limited to sites that are threatening to function or to life and definitely should be carefully administered in low total doses, 1,000 rads or less over one and a half to three weeks. Indeed, taxing the patient by "overirradiation" may impede the maturation of this disease and ultimately influence the outcome.
Ionizing radiations can be particularly injurious to the normal tissues of the very young. For example, it has been well established that the younger the patient, the greater the effect on normal tissues for a given dose of radiation. A total dose of 4,000 rads in four to five weeks administered to the spine of a neonatal patient can leave devastating skeletal and soft-tissue deformities, while the effects of the same dose in a 24-year-old would be much less severe. In the consideration of radiation therapy for Wilms's disease or neuroblastoma, tremendous weight must be given to the age of the patient and the potential gain to be derived from irradiation versus the risks of permanent damage to normal tissues. Obviously, in the neonatal patient with stage 1 Wilms's tumor or neuroblastoma, radiation therapy should seldom, if ever, be utilized.
Hodgkin's disease. The concepts of Hittle and Higgins - expressed in the article on Hodgkin's disease in the June, 1974, issue- are thought-provoking and deserve consideration. There is no evidence that a dose delivery rate of less than 1,000 rads per week is detrimental to cure. Indeed, undesirable normal-tissue side effects are reduced markedly by treatment with reduced daily doses of 175 rads or less in five increments per week. Ordinarily, the total dose need not exceed 4,000 rads. Is high-dose irradiation necessary in adjacent but unaffected regions? Perhaps not, in view of Dr. Vera Peter's experience. Can properly administered chemotherapy enable us to reduce amounts of ionizing radiations delivered to these young patients? Carefully controlled clinical trials to test these theses are probably indicated.
Of particular interest to the clinical radiobiologist are careful long-term observations resulting from entire central nervous system irradiation and irradiation of other "sanctuary sites" (abdomen, testes) in young acute lymphocytic leukemia patients. To date, these concepts of treatment appear well founded in statistically sound studies, but the long-term effects are yet to be documented and re-evaluated. Should an agent such as intrathecal methotrexate prove to be as effective as irradiation in central nervous system leukemia and long-term effects minimized, without question radiation therapy should be replaced in the therapeutic regimen.
In summary, radiation therapy, while a most valuable tool in the management of pediatrie cancers, must be judiciously administered. If alternative methods of treatment are available with similar beneficial effects and less normal-tissue morbidity, these should be utilized,