Magna-field irradiation: a note of caution.

Large-field (magna-field) irradiation, which has now been employed for several decades, is currently enjoying a resurgence in popularity because of success using total body irradiation (TBI) in the treatment of acute leukemias. While several centers have reported on the general use of magna-field irradiation, this issue presents a special symposium on its state-of-the-art use in the treatment of children with malignant disease. The contributed papers serve as useful reference documents and provide the reader with an up-to-date account of large-field irradiation as an effective systemic agent in children. The outlook and prognosis for a child with cancer are more optimistic than for the adult. Today, the overall cure rate for cancer in children exceeds 50%. Many of these childhood tumors share similar histological features, representing the so-called ‘small round-cell tumors of childhood.’ In general, they are both chemoresponsive and radioresponsive, accounting for much of the current therapeutic success. Why, then, explore the possibility of magna-field irradiation in such treatment? The reasons are simple. Although cure rates exceed 50% when optimal multidisciplinary therapy is used, the remaining children, almost 50% present a serious therapeutic challenge. While modern aggressive surgical techniques have greatly improved treatment, it is unlikely that surgery alone will further improve cure rates. Whereas many pediatric cancers are chemoresponsive, and multi-agent chemotherapy is much in vogue for the treatment of childhood cancers, further improvement using the currently available drugs is unlikely. The relatively limited number of drugs available for childhood cancers share similar mechanisms of action, with overlapping toxicities. Development of new agents is greatly needed, but is still some time away. In general, pediatric cancers are radiosensitive, and many are radiocurable. Although specific dose-response data are limited, clinical experience demonstrates that low doses of irradiation provide sufficient cell kill to effect local control for most clinical presentations of acute leukemias, malignant lymphomas, neuroblastoma, Wilms’ tumor, germ cell tumors, and many sarcomas. This local responsiveness to irradiation suggests its potential use as a systemic agent in advanced or chemotherapyrefractory clinical situations. Magna-field irradiation may be defined as TBI or as large-field irradiation, in practice ‘hemibody irradiation’ (HBI) or sequential HBI. Applications of TBI include: Bone marrow transplantation (BMT). Technically, BMT implies replacement of a patient’s blood-forming elements with those of another individual. It is used to eliminate indigenous bone marrow and suppress the immune system of the recipient (host), thereby permitting the bone marrow stem cells of the donor to engraft and prevent the host from rejecting the foreign cells. In aplastic anemia and selected congenital immunodeficiency states, TBI may be used to permit such engraftment and effect immunosuppression. In acute leukemias and certain malignant tumors, TBI also acts as a systemic antineoplastic agent in attempts to eradicate malignant cells. The relationship of the donor to the recipient defines this BMT procedure as syngeneic (donor cells from an identical twin, immunologically identical to the host) or allogeneic (the donor is antigenically similar to but not identical to the host-in practice usually a sibling). The most common settings for the use of TBI in BMT are acute non-lymphoblastic leukemia and acute lymphoblastic leukemia, refractory to first-line chemotherapy. Bone marrow reconstitution (BMR). The patient’s own bone marrow, removed prior to TBI and/or chemotherapy, is used to reconstitute the marrow, following doses of radiation therapy beyond that compatible with timely hematological recovery. TBI is used as an antineoplastic agent in this situation, often termed autologous BMT. Use of BMR requires that the patient’s bone marrow be free of tumor, either implied in the cbnical course of disease, or by specific ‘purging’ of the removed marrow-immunologically destroying residual neoplastic cells. Clinical use of BMR has included patients with neuroblastoma, Ewing’s sarcoma, B cell malignant lymphoma, and primary CNS tumors. Adjuvant systemic therapy (AST). In tumor presentations where distant metastases represent the primary