Primary extracranial neuroblastoma with central nervous system metastases characterization by clinicopathologic findings and neuroimaging.

The authors report the clinicopathologic and neuroimaging findings in ten children with primary abdominal or thoracic neuroblastoma who relapsed in the central nervous system (CNS) without evidence of concurrent intracranial extension from adjacent bone, dura, or dural sinus metastases. At diagnosis, the patients ranged in age from 0.3 to 4.5 years (median, 2 years). Their times to CNS relapse ranged from 2 to 34 months from diagnosis. In seven patients the relapse occurred from 1 to 14 months after elective discontinuation of therapy. In four patients, the CNS relapse was the primary (isolated) adverse event. Four patients could not be treated at the time of relapse, and they died within 7 days of progressive CNS disease. In the remaining group, craniospinal irradiation with or without administration of a platinum compound and an epipodophyllotoxin caused complete CNS remissions lasting 4, 5, 16, and 62+ months. Neuroimaging and autopsy findings indicated that cerebrospinal fluid is the major pathway for neuraxis dissemination by neuroblastoma cells. There was no evidence of dural penetration in any patient. The possibility of relapse in the neuraxis should be considered for any patient with neuroblastoma who had neurologic deterioration. A combination of craniospinal radiation and administration of a platinum compound and an epipodophyllotoxin will induce complete responses in some patients with neuraxis involvement by neuroblastoma, but the risk of subsequent failure outside the CNS remains high.

Postoperative radiotherapy in the treatment of extremity soft tissue sarcomas.

From 1966 to 1983, 50 patients with extremity soft tissue sarcomas were treated with wide local excision and postoperative radiotherapy at the Mallinckrodt Institute of Radiology. The median follow-up was 70 months (range 28 to 168). Grade was the most significant factor affecting survival: all 11 patients with well differentiated tumor survived versus 6/8 patients with moderate and 17/31 patients with poorly differentiated tumors (p less than 0.01). In addition, lymph node involvement at diagnosis conferred a worse prognosis with only 2/5 patients alive after treatment (p less than 0.05). Eleven of 50 (22%) failed locally. Factors affecting local control included gross residual tumor after operation and limited treatment volume. Among the 35 patients who did not have gross residual tumor or limited treatment volume, two patients who received less than 5000 cGy failed locally versus 1/18 patients who received between 5000-6000 cGy and 2/15 patients who received more than 6000 cGy. Microscopically positive margins and a volume encompassing less than the total muscular compartment was not associated with an increase in the incidence of local failure. Eight patients developed local complication: five due to retreatment for local recurrence. Overall, 24/26 patients who are alive have had their limbs preserved with normal function.

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.

Wilms' tumor: reduced-dose radiotherapy in advanced-stage Wilms' tumor with favorable histology.

Fifty-two children with favorable histology Wilms' tumor who had residual abdominal disease (Surgical Stages III and IV) were treated from 1979 to 1988 on a protocol designed to assess the effectiveness of reduced radiation doses. All patients received three-agent chemotherapy, beginning within 1 week after surgery. To permit assessment of disease response to initial chemotherapy, radiation therapy was delayed for a median of 28 days after surgery (range, 14-71 days). Total doses of abdominal radiation were limited to 12 Gy, given as 150 cGy daily fractions; 18 patients with Stage IV disease received 12 Gy bilateral pulmonary irradiation. Two year disease-free survival was 85% and 71% for Stage III and IV, respectively (p = .24). Abdominal relapses occurred in 3 cases (5.7%). The interval between surgery and initiation of irradiation was not related to disease-free survival. Of several patient and disease-related factors analyzed, only patient age was related to outcome. Disease-free survival was 100% at 3 years for children under the age of 3 versus 78% for children greater than age 3 (p = .05). Reduced-dose abdominal radiotherapy in conjunction with multi-agent chemotherapy and surgery provided excellent disease control with minimal toxicity in advanced-stage, favorable histology Wilms' tumor.

Pediatric nasopharyngeal carcinoma: long term follow-up of 29 patients.

Twenty-nine untreated children diagnosed with nasopharyngeal carcinoma were consecutively admitted to St. Jude Children's Research Hospital from 1962 to 1986. The age of the patients ranged from 6 to 19 years (median of 13) at diagnosis. Histologically, all had lymphoepithelioma. Patients were retrospectively staged in the American Joint Committee System. Disease extent was T1 (n = 5), T2 (n = 7), T3 (n = 9), T4 (n = 8); N0 (n = 1), N2 (n = 7), N3 (n = 21). Two patients had distant metastasis (M1) on admission, both ultimately succumbed to their disease. Twenty-seven patients were seen initially without metastatic disease: one received pre-irradiation vincristine, 17 were treated with concomitant radiotherapy and cyclophosphamide. From 1981 to the present, four patients received pre-irradiation and one received post-irradiation cisplatin-bleomycin, vinblastine (CDDP-BLEO-VLB) regimens. Four patients received radiotherapy alone. All patients completed chemotherapy and radiation therapy. Twenty-five patients had complete tumor clearance and four had a partial response. Overall, 14 patients are alive continuously without relapse with a median follow-up of 11 years (range 4 to 20). All patients who relapsed did so within 2 years postirradiation. Four patients failed locally--all had advanced (T3-T4) local disease at presentation and three of the failures were at the margin of treatment portals. Thirteen patients failed with distant metastasis. The major prognostic factor in these patients was the local extent of disease. Among the 27 M0 patients, all ten patients with T1-2 tumors are disease-free, whereas four of nine patients with T3 and two of eight patients with T4 tumors are alive and well. In the 16 patients who are long term survivors, eight have mild neck atrophy, two have shortening of the clavicles; except for one patient who required a neck brace for shoulder drop, all had normal function. Among the seven pre-pubertal patients who are long term survivors, three have decreased growth, including one with documented decreased growth hormone. Two patients developed irregular menstrual periods. One patient developed hypothyroidism, and another had a thyroid adenoma. One patient developed bleomycin pneumonitis and one patient who received pre- and post-irradiation chemotherapy died of laryngeal edema and fibrosis, in remission. Radiotherapy is the major modality in the therapy of childhood nasopharyngeal carcinoma. The long term toxicity of radiotherapy plus or minus chemotherapy is acceptable. In early stage tumors (T1-2, N1-2), radiotherapy alone (55-60 Gy) appears to be sufficient for disease control.(ABSTRACT TRUNCATED AT 400 WORDS)

Hodgkin's disease in children.

This article discusses the presentation and evolution of therapy of pediatric Hodgkin's disease, contrasted with developments in adults. The issues of staging, treatment, and toxicity of radiotherapy, chemotherapy, and combined modality therapy are discussed. Recommendations for therapy are presented.