Abnormal growth patterns and adult short stature in 115 long-term survivors of childhood leukemia.

Significant growth retardation was found in 115 survivors of childhood acute lymphoblastic leukemia (ALL) who had completed their growth. These children were diagnosed before 12 years of age and treated on four protocols in a single institution; all received either cranial (n = 78) or craniospinal (n = 37) prophylactic irradiation. Patients' heights at diagnosis were within expected ranges, but final heights were greater than or equal to 1 SD below population means in 74% of cases and greater than or equal to 2 SD in 37%. Effects on growth were more pronounced for children who had received craniospinal irradiation, but decrements were also significant in the cranial irradiation group, with adult heights greater than or equal to 2 SD below population norms in 32%. Growth retardation was significantly greater (P less than .0001) in children who had earlier disease onset. Growth deceleration occurred not only during chemotherapy but during a later period that followed an interval of improved growth in many cases. Thus, late decrements in growth may be missed in studies that do not follow patients until they have attained final heights. These findings indicate that abnormally short stature among survivors of ALL merits further clinical and research attention.

Local-regional non-rhabdomyosarcomatous soft tissue sarcomas of the head and neck.

Between 1962 and 1987, 112 consecutive patients were treated at St. Jude Children's Research Hospital for soft tissue sarcomas of the head and neck region; 18 of these children (16%) had histologic subtypes other than rhabdomyosarcoma. We evaluated the impact of surgery, postoperative chemotherapy, and irradiation on local control and survival in these cases. Three patients who had complete resection of tumors and received no further treatment are alive without disease at 36, 42, and 162 months. Local control was achieved in 1 of 2 patients with microscopic residual tumor and 4 of 9 patients with gross residual tumor who were treated with irradiation (2500-5040 cGy). Chemotherapy was the only postoperative treatment in three patients; only one achieved lasting local control. One patient was treated with irradiation only; his primary site showed no tumor cells at autopsy following an automobile accident. Overall, local control was achieved in 50% of patients; the disease-free survival rate at 3 years was 44%. The prognosis for patients with nonresectable tumors remains unsatisfactory because of the difficulty in securing local control. A revised therapeutic approach to these patients is presented.

Capsular and vascular invasion: important prognostic factors in Wilms' tumor.

The influence of capsular and vascular invasion on prognosis was determined retrospectively in 52 children with Wilms' tumor. Local recurrence was more prevalent (0.26) in patients with rupture or capsular invasion than in any other group. Inadequate postnephrectomy irradiation or infiltration of the liver by nephroblastoma cells appeared to be predisposing factors in the development of these reccurrences. Of the 26 patients with gross or microscopic vascular invasion, 13 developed metastasis. This proportion was significantly higher than in patients without vascular involvement (p less than 0.05). These observations emphasize the importance of microscopic detection of capsular and vascular invasion in staging of Wilm's tumor.

Adjuvant multiple drug chemotherapy for osteosarcoma of the extremity.

Results of treatment for osteosarcoma of the extremity have been poor with metastases usually causing death within 2 years following diagnosis. Because of the great risk of development of metastases, 20 patients have received adjuvant chemotherapy with Adriamycin, cyclophosphamide and high-dose methotrexate-leucovorin rescue for up to 12 months following amputation for osteosarcoma. Sixteen of these patients are surviving; 11 are free of evident tumor from 6 to 34 months following amputation. Five patients were found to have pulmonary metastases while receiving chemotherapy and three patients developed metastases following completion of chemotherapy. One patient died following her third treatment with high-dose methotrexate-leucorovin rescue. Other toxicity included nausea, vomiting, mucosal ulcerations, infections, hematologic abnormalities, changes in kidney and liver functions tests, and minor coagulation abnormalities. The natural history of osteosarcoma may have been modified by the use of these agents for periods exceeding the median time to predicted detection of pulmonary metastases. Microscopic metastases of some patients were eradicated by this adjuvant chemotherapy. For patients who developed metastases, these metastases were delayed in their time of detection and in their number at the time of detection.

The role of surgical resection when combined with chemotherapy and radiation in the management of pelvic rhabdomyosarcoma.

With the development of combined chemotherapy and radiation therapy for embryonal rhabdomyosarcoma, the role and extent of surgical resection of these pelvic tumors need to be defined. Thirty-six children with pelvic genitourinary rhabdomyosarcoma seen at St. Jude Children's were managed on protocols combining surgical resection and radiation, and chemotherapy. Ten children presented with cervical-vaginal tumors, which were managed with combined therapy; the surgical resection was histovaginectomy in eight and pelvic exenteration in one. Eight of the ten are free of disease from 1 to 14 years. Twelve children presented with bladder and prostate tumors, which were resected with segmental cystectomy in four cases, biopsy in five, and pelvic exenteration in three. All received combination therapy and six of the twelve are surviving free of disease from 6 months to 16 years. Fourteen children presented with paratesticular rhabdomyosarcoma. Chemotherapy was combined with radical orchiectomy in all cases. Retroperitoneal node dissection was done in nine and five had inguinal node dissection. Nine of the 14 are surviving NED from 2 to 16 years. One patient died, free of disease, with complications of combination therapy. The results of this review supports the approach of combining chemotherapy, radiation, and complete surgical resection.

Testicular relapse in children with acute nonlymphoblastic leukemia.

The clinical course and other distinctive features of five children who developed a testicular relapse 4 months to 25 months after the diagnosis of acute nonlymphoblastic leukemia (ANLL) are described. The chief presenting feature at relapse was painless testicular enlargement, as is also seen in children with acute lymphoblastic leukemia who relapse in the testes. By French-American-British convention, the malignant cells were classified as M4 (myelomonoblastic) in four cases and M2 (myeloblastic) in one. All children received a course of multiagent reinduction chemotherapy and all but one received local irradiation to the testes. Only one of these children, whose relapse was a late event after elective cessation of therapy, is a long-term survivor. A comparison with six previously published cases shows similar clinical characteristics and outcome. Given the poor responses of such patients to conventional treatment, it seems worthwhile to consider the use of intensive reinduction chemotherapy with concomitant bilateral testicular irradiation followed by remission intensification and an autologous or allogenic marrow transplant.

Thyroid dysfunction and neoplasia in children receiving neck irradiation for cancer.

The reported relationship of radiation exposure and thyroid carcinoma stimulated this retrospective study of 298 patients treated at St. Jude Children's Hospital with radiation therapy to the neck for childhood cancer to identify patients who developed subsequent thyroid abnormalities. This series includes 153 patients with Hodgkin's disease, 95 with acute lymphocytic leukemia, 28 with lymphoepithelioma, and 22 with miscellaneous tumors. Inclusion in the study required 5 years of disease-free survival following therapy for their original tumor, which included thyroid irradiation. Follow-up has been 100%. Most patients also received chemotherapy. Seventeen patients were found to have decreased thyroid reserve with normal levels of free triiodothyroxine (T3) or free thyroxin, (T4) and an elevated level of thyroid-stimulating hormone (TSH). In nine patients hypothyroidism developed, with decreased T3 or T4 levels and an elevated level of TSH. One hyperthyroid patient was identified. Two patients had thyroiditis, and seven had thyroid neoplasms: (carcinoma in two, adenoma in two, colloid nodule in one, and undiagnosed nodules in two). This survey has demonstrated an increased incidence of thyroid dysfunction and thyroid neoplasia when compared to the general population. The importance of long-term follow-up for thyroid disease is emphasized in patients who have received thyroid irradiation. The possible role of subclinical hypothyroidism with TSH elevation coupled with radiation damage to the thyroid gland as a model for the development of neoplastic disease is discussed.