The treatment of choice for localized Hodgkin's disease in children has evolved to the use of combined modality therapy with a decreased number of chemotherapy courses and reduced-dose irradiation to areas of involved disease. The use of chemotherapy alone is also currently under evaluation. The goal has been to maintain high cure rates while reducing the late effects that are especially seen in children.
Adolescent patients who have achieved maximum growth and have localized childhood Hodgkin's disease (pathologically staged I and II) may be treated as adults with standard dose radiation alone with 35-45 Gy delivered to the neck, chest, and axilla (mantle) followed by an abdominal para-aortic field. Some of these patients will have disease recurrence and will require subsequent chemotherapy for cure. In the Intergroup Hodgkin's disease study, a high relapse rate was observed in patients treated with involved-field radiotherapy alone. For patients who have not yet achieved full growth, chemotherapy along with involved-field radiotherapy at a lower dose is generally used. Chemotherapy alone for localized disease has been used in developing countries with some success and accumulating experience with this approach suggests that results equivalent to those of combined modality therapy are achieved.
Attempts to limit or eliminate radiation are important in view of substantial evidence of an association with the late development of solid tumors, especially more than 10 years after therapy.
Patients whose mediastinal disease is massive, i.e., more than one third the maximal thoracic diameter, or with tumor involving the pericardium or chest wall, should be treated with chemotherapy and radiotherapy, even if they have stage I or II disease. However, mass size by itself is not a contraindication to primary radiotherapy; the relationship of the mass to underlying normal tissue is a strong consideration. Monitoring of mediastinal disease is best accomplished by 67-Gallium SPECT imaging.
The treatment of choice for advanced childhood Hodgkin's disease and for patients who relapse after radiation therapy is combination chemotherapy with one of the regimens that has been shown to produce prolonged remissions. The need for low-dose radiotherapy is under study. There are important long-term side effects of treatment that warrant consideration, including the potential risks of treatment-related second neoplasms (e.g., acute myeloid leukemia, non-Hodgkin's lymphoma, and breast cancer), loss of fertility, growth considerations, and long-term organ dysfunction (e.g., thyroid, heart, lung). Physicians should discuss these side effects in detail with patients when treatment is selected. Careful follow-up of treated patients is essential.
The type of treatment administered may influence the later risk of secondary acute leukemia, as combined modality therapy with certain chemotherapeutic regimens and irradiation is associated with increased risk compared with either treatment alone. The risk of a secondary acute leukemia with irradiation alone is much less than with chemotherapy. There may also be a dose response-effect: with an increased dose of chemotherapy there is an increased risk of secondary leukemia; this risk may be increased after splenectomy. It is possible that newer combination chemotherapy regimens will prove to be less leukemogenic than older combinations that included alkylating agents such as mechlorethamine and procarbazine.
The use of radiotherapy is associated with an increased risk of development of solid tumors, particularly breast and thyroid cancer, within the port. The cumulative risk of developing breast cancer has been estimated to be as high as 35% at 40 years of age, depending on radiation dose and age at diagnosis, with the greatest risk in those who were treated from age 10 years to age 16 years. Thus, all female patients should be informed of the breast cancer risk and breast self examination should be initiated at an early age. (A separate summary containing information on screening for breast cancer is available in PDQ.) In sexually mature males who will undergo combination chemotherapy or pelvic irradiation, consideration should be given to storing sperm, since seminiferous tissue is often irreparably damaged by chemotherapy or scattered irradiation. Sperm storage is complicated by the fact that many patients have low sperm counts at presentation. In order to maintain fertility in males, etoposide has been substituted for procarbazine in combination chemotherapy regimens, since it causes less gonadal damage. Females may also become infertile and have early menopause. The risk may be decreased by oophoropexy to move gonads out of the radiotherapy field during laparotomy if pelvic irradiation is planned.
Placement of titanium clips at the splenic hilum is strongly recommended to facilitate radiation therapy planning to shield the left kidney when the para-aortic nodes and splenic pedicle are to be irradiated. In addition, children will often show localized growth abnormalities after full-dose radiation. For example, the neck may have a smaller circumference or the upper chest may be poorly developed if these areas are irradiated.
The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.
