Melanoma as a second malignant neoplasm after childhood cancer.

BACKGROUND: As more children survive childhood cancers, the population at risk for second malignant tumors increases. The development of melanoma as a second malignant tumor is not well described. METHODS: The M.D. Anderson Cancer Center's 50-year experience with patients who developed melanoma after treatment of a childhood cancer was retrospectively reviewed. RESULTS: One hundred seventy-two patients with a second malignancy were identified; 11 patients had melanoma as a second malignancy. The most common first malignancies were Hodgkin's disease, brain tumors, and retinoblastomas. Melanoma developed in an irradiated field in 4 patients. Six patients had lymphatic or distant metastasis at diagnosis. Five of 11 patients died of melanoma. CONCLUSIONS: Factors contributing to melanoma as a second malignancy may include genetic factors and the effects of chemotherapy and radiation. Survivors of childhood malignancy should be considered at risk for developing melanoma, and suspicious pigmented lesions should be carefully evaluated.

Long-term effects of radiotherapy administered in childhood for the treatment of malignant diseases.

BACKGROUND: The use of radiotherapy for the treatment of childhood malignancy has improved long-term survival significantly, and many treated children now survive well into adulthood. As a consequence, long-term effects of childhood irradiation are being seen with increasing frequency. METHODS: The medical records of 236 patients who had been treated for malignant disease with radiotherapy during childhood were examined to determine the long-term effect of the radiation on their growth and development. RESULTS: Mean treatment dose was 35.5 Gy; mean age at treatment was 7.2 years; and mean follow-up was 14.5 years. Adjuvant chemotherapy was given to 82%. Some degree of bone deformity (usually with overlying soft-tissue hypoplasia) was seen in 40%; 21% developed some type of endocrine deficiency; 30% developed atrophic skin changes; and 7% developed second malignancies. The incidence of bone deformity and hormonal deficiency increased with the radiation dose; the incidence of second malignancy was independent of dose. Bone deformities were more common when radiation was administered before the age of 2 years. CONCLUSIONS: The consequences of radiotherapy in childhood are significant and must be considered when planning treatment. Even when treatment is essential, families should be informed of the possibility of growth disturbance to prevent subsequent misunderstanding.

Radiation-induced changes in long-term survivors of childhood cancer after treatment with radiation therapy.

This article has provided an account of the delayed effects after successful treatment for childhood cancer. Particular emphasis has been placed on sequelae induced by radiation therapy. Chemotherapy-related complications that may simulate or aggravate these sequelae also are recorded. The alterations induced by radiation therapy and chemotherapy are not limited to the organs and tissues described in this article. Subtle, and at times psychologically devastating, sequelae also may be encountered (eg, sterility due to radiation and chemotherapeutic effects on the gonads). However, an attempt has been made only to identify those complications that may be more readily detected by means of radiographic studies. It is recommended that ongoing surveillance of the long-term successfully treated childhood cancer survivor be conducted in order to detect such complications. Early detection will assist in implementing appropriate treatment, minimizing delayed effects, and maximizing the quality of life. Periodic radiographic studies of previously radiated areas at regular intervals therefore appears appropriate.

Thyroid gland: US in patients with Hodgkin disease treated with radiation therapy in childhood.

The authors retrospectively assessed with sonography the prevalence of thyroid gland abnormalities in 30 patients who underwent radiation therapy for Hodgkin disease between 1962 and 1984. Doses ranged from 3,000 to 4,500 rad (3,000-4,500 cGy). Abnormalities were found in the sonograms of 24 patients and included unilateral (n = 6) or bilateral (n = 2) atrophy; multiple hypoechoic lesions smaller than 0.75 cm (n = 18); and dominant cystic (n = 2), solid (n = 3), or complex lesions (n = 4) larger than 0.75 cm. The risk of development of an abnormality increased as the time from irradiation increased and was comparable between patients who did and did not receive chemotherapy as part of the treatment regimen. Although the pathologic correlates of the various abnormalities seen on sonograms may differ, the findings indicate a need for long-term follow-up of patients who underwent cervical irradiation for Hodgkin disease.

Neuropsychological effects of childhood cancer treatment.

The potential neuropsychological effects of treatment were investigated in 124 childhood cancer patients. Children were classified into groups on the basis of treatment modality and treatment status. All patients received systemic chemotherapy. Other treatment modalities included intrathecal chemotherapy and intrathecal chemotherapy plus central nervous system radiation therapy. Treatment status was determined by whether children were newly diagnosed patients in active treatment or long-term survivors of cancer. This classification resulted in five groups; group 1 (n = 29)--children with newly diagnosed disease who were receiving intrathecal chemotherapy; group 2 (n = 21)--children with newly diagnosed disease who were receiving systemic chemotherapy without central nervous system treatment; group 3 (n = 24)--long-term survivors who had received intrathecal chemotherapy; group 4 (n = 25)--long-term survivors who had received intrathecal chemotherapy plus cranial radiotherapy; and group 5 (n = 25)--long-term survivors who had received systemic chemotherapy only (no specific central nervous system treatment). Groups were compared by using multivariate analysis of variance on sets of neuropsychological test variables that represent major cognitive domains. Results of comparisons indicated significant group differences for most dependent-variable sets. Follow-up pairwise comparisons showed that the group of long-term survivors who had received intrathecal chemotherapy plus cranial radiotherapy consistently obtained lower test scores than the other four groups. These findings are consistent with results of previous studies, thus indicating that intrathecal chemotherapy plus cranial radiotherapy is associated with significant effects on neuropsychological performance. Comparisons among newly diagnosed and long-term groups of patients who did not receive cranial radiotherapy yielded null results on measures of higher-order cognitive functions. However, significant group differences were observed on measures of fine-motor and visual-motor skills; newly diagnosed groups obtained lower scores than the nonirradiated long-term survivor groups. Findings were attributed to chemotherapy-induced peripheral neuropathy that differentially affected the newly diagnosed groups.

Dental and maxillofacial abnormalities in long-term survivors of childhood cancer: effects of treatment with chemotherapy and radiation to the head and neck.

Sixty-eight long-term survivors of childhood cancer were evaluated for dental and maxillofacial abnormalities. Forty-five patients had received maxillofacial radiation for lymphoma, leukemia, rhabdomyosarcoma, and miscellaneous tumors. Forty-three of the 45 patients and the remaining 23 who had not received maxillofacial radiation also received chemotherapy. Dental and maxillofacial abnormalities were detected in 37 of the 45 (82%) radiated patients. Dental abnormalities comprised foreshortening and blunting of roots, incomplete calcification, premature closure of apices, delayed or arrested tooth development, and caries. Maxillofacial abnormalities comprised trismus, abnormal occlusal relationships, and facial deformities. The abnormalities were more severe in those patients who received radiation at an earlier age and at higher dosages. Possible chemotherapeutic effects in five of 23 patients who received treatment for tumors located outside the head and neck region comprised acquired amelogenesis imperfecta, microdontia of bicuspid teeth, and a tendency toward thinning of roots with an enlarged pulp chamber. Dental and maxillofacial abnormalities should be recognized as a major consequence of maxillofacial radiation in long-term survivors of childhood cancer, and attempts to minimize or eliminate such sequelae should involve an effective interaction between radiation therapists, and medical and dental oncologists.

Neuropsychologic assessment of long-term survivors of childhood leukemia.

Thirty-two long-term survivors of childhood leukemia who were followed up at the University of Texas M. D. Anderson Hospital were evaluated with a battery of 17 neuropsychologic tests. These tests were selected to assess the development of cognitive skills and functions associated with brain impairment in children. Statistically significant differences were found between the group of children given CNS irradiation and the nonirradiated group on full-scale IQ and verbal IQ scores, mathematics skills, constructional skills, and memory for spatial material. Of particular interest was the absence of differences in language-based measures of verbal memory and the presence of group differences on measures of memory for spatial material. While the sample size was small, the findings delineate specific areas likely to be affected. These results indicate the need for caution when including cranial irradiation in CNS prophylaxis. When any CNS treatment is given, it seems appropriate that provisions be made for assessment and remediation of affected skills.

Active sperm production after cancer chemotherapy with doxorubicin.

The sperm production of 14 cancer patients who received doxorubicin was examined after cessation of therapy. Doxorubicin was used in several multiple-drug protocols for the treatment of various malignancies. Seven patients also received radiotherapy to different sites. Total cumulative doses of doxorubicin ranged from 145 to 625 mg./m.2. Sperm concentration, motility, morphology and the frequency of quinacrine-stained sperm with 2 fluorescent bodies (2F sperm) were measured 7 to 79 months after discontinuation of doxorubicin. Of the patients 6 remained azoospermic, 3 were oligospermic and 5 were normospermic. Sperm motility among the 8 patients with sperm ranged from 20 to 80 per cent. Morphology and 2F sperm distributions were not significantly different from controls. We conclude that, in contrast with the mechlorethamine, vincristine, procarbazine and prednisone protocol, active sperm production within relatively short recovery times is possible after treatment with protocols that include doxorubicin.

Radiation induced osteochondroma in long-term survivors of childhood cancer.

The records of 200 long term survivors of childhood cancer where reviewed. Radiation induced osteochondromata were detected in 12 patients (6%). Radiation had been administered in doses ranging from 1250 R (approximately 1500 rad) to 5500 rad between the ages of 8 months and 11 1/2 years. Radiation-induced osteochrondromata were detected 3 to 13 1/2 years later, with a median of 5 years. The osteochrondomata were single in 7 patients and multiple (2-4) in 5. Two occurred at sites of previous thoracotomy. Factors related to radiation induced osteochondromata are discussed.

Hypothalamic, pituitary and thyroid dysfunction after radiotherapy to the head and neck.

One hundred-ten patients who had nasopharyngeal cancer and paranasal sinus tumors and were free of the primary disease were studied one to 26 years following radiotherapy. There were 70 males and 40 females ranging in age from 4 to 75 years, with a mean age of 36.5 years. During therapy both the hypothalamus and the anterior pituitary gland were in the field of irradiation. The radiation dose to the hypothalamus and the anterior pituitary gland was estimated to be 400 to 7500 rad with a median dose of 5618 rad to the anterior pituitary gland and a median dose of 5000 rad to the hypothalamus. We found evidence of endocrine deficiencies in 91 of the 110 patients studied. Seventy-six patients showed evidence of one or more hypothalamic lesions and 43 patients showed evidence of primary pituitary deficiency. Forty of the 66 patients who received radiotherapy to the neck for treatment or prevention of lymph node metastasis showed evidence of primary hypothyroidism. The range of the dose to the thyroid area was 3000 to 8800 rad with a median of 5000 rad. One young adult woman who developed galactorrhea and amenorrhea 2 years following radiotherapy showed a high serum prolactin level, but had normal anterior pituitary function and sella turcica. She regained her menses and had a normal pregnancy and delivery following bromocriptine therapy. These results indicate that endocrine deficiencies after radiotherapy for tumors of the head and neck are common and should be detected early and treated. Long-term follow-up of these patients is indicated since complications may appear after the completion of radiotherapy.