Philip Stanley

Effects of Medulloblastoma Resections on Outcome in Children: A Report from the Children's Cancer Group

We reviewed the data of children with high-stage primitive neuroectodermal tumors (medulloblastomas) who were treated on Childrens Cancer Group-921 protocol to evaluate the correlation between tumor resection and prognosis. Patients enrolled in the study had either tumors that were operatively categorized to be Chang tumor stage 3b or 4, postoperative residual tumors > 1.5 cm2, or evidence of tumor dissemination (Chang metastasis Stages [M Stages] 1-4) at diagnosis. Resections were analyzed in two ways, as follows: 1) by the extent of resection (percent of the tumor that was removed), as estimated by the treating neurosurgeon; and 2) by the extent of residual tumor (how much of the tumor was left), as estimated from postoperative scans. Two hundred and three children were enrolled in the study with institutional diagnoses of primitive neuroectodermal tumors-medulloblastomas; diagnoses were confirmed by central neuropathological review in 188 patients. Progression-free survival (PFS) at 5 years was 54% (standard error, 5%). As in previous Childrens Cancer Group studies, age and M stage correlated with survival; PFS was significantly lower in children 1.5 to 3.0 years old at diagnosis and in those with any evidence of tumor dissemination (M Stage 1-4). On univariate analysis, neither extent of resection nor extent of residual tumor correlated with PFS. However, adjusting for other factors, extent of residual tumor was important; PFS was 20% (standard error, 14%) better at 5 years in children with no dissemination (M Stage 0) who had < 1.5 cm2 of residual tumor (P = 0.065) and was 24% (standard error, 14%) better at 5 years in children > 3 years old with no tumor dissemination (M Stage 0) and with < 1.5 cm2 residual tumor (P = 0.033). On the basis of our observations, we conclude that extent of tumor resection, as estimated by the neurosurgeon, does not correlate with outcome but that extent of residual tumor does correlate with prognosis in certain children (those who are > 3 years old, with no tumor dissemination). In contrast to age and M stage, the major factors associated with outcome, residual tumor is an important variable in outcome, one that neurosurgeons can control.

Results of a Prospective Randomized Trial Comparing Standard Dose Neuraxis Irradiation (3,600 cGy/20) with Reduced Neuraxis Irradiation (2,340 cGy/13) in Patients with Low-Stage Medulloblastoma

PURPOSE To determine in a prospective randomized trial the effect on survival, progression-free survival, and patterns of relapse of a decrease in the neuraxis radiation dose from 3,600 cGy in 20 fractions to 2,340 cGy in 13 fractions in patients with newly diagnosed medulloblastoma between 3 and 21 years of age with low T stage (T1, T2 and T3A), minimal postoperative residual tumor, and no evidence of dissemination (M0). METHODS AND MATERIALS Between June 1986 and November 1990, the Childrens Cancer Group and the Pediatric Oncology Group randomized 126 patients in a two-arm study comparing the two different doses of neuraxis irradiation. In both arms, the posterior fossa received 5,400 cGy in 30 fractions. All patients were staged with myelography, postoperative lumbar cerebrospinal fluid cytology, and postoperative contrast-enhanced cranial computerized tomography to ensure no evidence of dissemination and no more than 1.5 cm3 residual tumor volume. Overall survival, progression-free survival, and patterns of recurrence were carefully monitored. Prospective endocrine and psychometric studies were performed to determine the benefit of decreasing the neuraxis radiation dose. RESULTS Following an interim analysis at a median time on study of 16 months, the study was closed, since a statistically significant increase was observed in the number of all relapses as well as isolated neuraxis relapses in patients randomized to the lower dose of neuraxis radiation. CONCLUSIONS In patients with newly diagnosed medulloblastoma considered to have a good prognosis on the basis of low T stage, minimal residual tumor after at least subtotal resection, and no evidence of dissemination after thorough evaluation, there is an increased risk of early relapse associated with lowering the dose of neuraxis radiation from 3,600 cGy in 20 fractions to 2,340 cGy in 13 fractions.

Prognostic Factors in Children with Supratentorial (Nonpineal) Primitive Neuroectodermal Tumors

Supratentorial primitive neuroectodermal tumors (S-PNETs), which have also been called cerebral neuroblastomas, have been considered to be the hemispheric equivalent of posterior fossa medulloblastomas. Twenty-seven children with S-PNETs (excluding pineoblastomas) which were confirmed by central pathology review were treated on the CCG-921 protocol from 1986 to 1992. After operation, all patients were staged with CSF cytology and spinal myelography or magnetic resonance scans and were treated with craniospinal irradiation and chemotherapy. Data from these 27 patients have been reviewed to evaluate neurosurgical treatment, survival, and prognostic variables that correlate with survival. Overall survival at 5 years was 34% (SE 20%) and progression-free survival (PFS) was 31% (SE 18%), which is lower than the survival of patients with posterior fossa PNETs (medulloblastomas). PFS was significantly worse in children 1.5-3 years of age at diagnosis and in those with evidence of tumor dissemination at the time of diagnosis. Large preoperative tumors were more likely to be associated with greater than 1.5 cm2 residual tumor postoperatively. Neurosurgeons estimated that less than 1.5 cm2 of residual tumor was present in 52% of the cases; postoperative scans confirmed that in 58%. For children with less than 1.5 cm2 residual tumor, postoperative survival at 4.0 years was 40% (SE 22%); for those with greater than 1.5 cm2 residual tumor, survival was 13% (SE 8%). The difference did not reach statistical significance, due to small numbers in this series, though a trend did exist (p = 0.19). Large series will be required to clarify the effects of extent of resection on survival.

Feasibility and toxicity of chemoembolization for children with liver tumors.

PURPOSE To determine the feasibility, toxicity, and efficacy of hepatic arterial chemoembolization (HACE) in pediatric patients with refractory primary malignancies of the liver. PATIENTS AND METHODS Six patients with hepatoblastoma (HB), three with hepatocellular carcinoma (HCC), and two with undifferentiated sarcoma of the liver were treated with HACE every 2 to 4 weeks until their tumors became surgically resectable or they showed signs of disease progression. All but one newly diagnosed patient with HCC had previously received systemic chemotherapy. RESULTS All patients with HB and HCC responded to HACE, as measured by imaging studies and alpha-fetoprotein levels. Surgical resection (complete or microscopic residual disease) was feasible in five of 11 patients, and three patients remain alive with no evidence of disease. Elevated liver transaminase and bilirubin levels were seen after each one of the 46 courses of HACE. Other toxicities included fever, pain, nausea, vomiting, and transient coagulopathy. CONCLUSION HACE is feasible, well tolerated, and effective in inducing surgical resectability of primary hepatic tumors in children.

Infantile Hepatic Hemangiomas Clinical Features, Radiologic Investigations, and Treatment of 20 Patients

The clinical features, radiologic investigation, and treatment of 20 infants with hepatic hemangiomas are presented. Palpable abdominal mass (n = 18) and cardiac failure (n = 11) were the common presenting features. Nine patients had hyperconsumptive coagulopathy. Seven patients had other hemangiomas. Ultrasound (n = 15) showed the number and distribution of the hemangiomas within the liver. Hypoechoic and hyperechoic elements were present in addition to prominent vascular channels and diminished caliber of the distal aorta. Radionuclide sulfur colloid (n = 12) and labeled red blood cell (n = 7) studies showed the distribution and vascularity of the hemangiomas. Computed tomography (n = 8) revealed central hypointensity with marked peripheral enhancement after contrast. Arteriography now performed only as a prelude to therapeutic embolization demonstrated hypervascularity in each patient, contrast pooling in six and early draining veins in five. Magnetic resonance scanning (n = 3) showed decreased signal intensity on T1 images and high intensity signal on T2. In two patients, there was resolution or improvement of the hemangiomas without therapy. Four patients had surgery (lobectomy [2], trisegmentectomy [1], and surgical evacuation of a central hematoma [1]). Steroids and radiation were given to seven patients, and one patient also required therapeutic embolization. Steroids were the initial therapy in five patients, one of whom later required therapeutic embolization and another cyclophosphamide. Two patients were treated initially with radiation therapy, one of whom also needed emergency hepatic artery ligation. Seventeen of the 20 patients are alive and well from 6 months to 14 years after diagnosis.

Renovascular hypertension in children and adolescents.

Renovascular disease often leads to hypertension in children. The most frequent cause is fibromuscular dysplasia of focal type affecting main and peripheral arteries. Diastolic readings in excess of 110 mm Hg with normal serum creatinine and urinalysis are suggestive of renovascular disease. Excretory urography was positive in 65% of patients with unilateral disease. Radionuclide scans complement a positive excretory urogram but may be positive when the urogram is negative. Plasma renin activity was raised in the majority of patients; if the patient does not have peripheral branch stenosis, the renal vein renin ratio will lateralize in unilateral renal disease. The overall results of surgery are encouraging: 86% of surgical procedures alleviated hypertension in unilateral disease.

Multicentric giant cell tumor: report of five new cases

The typical giant cell tumor (GCT) is a solitary neoplasm that occurs in the epiphysis or epimetaphysis of long bones. GCT is seen with a slightly increased frequency in females, and 70% of patients are between 20 and 40 years of age at the time of presentation. Multicentric giant cell tumor (MGCT; two or more centers) is an unusual variant of GCT. Patients with MGCT are likely to be younger than those with a solitary lesion. The multicentric variety is often of a higher stage at diagnosis and is more often associated with a pathological fracture than the unifocal tumor. We are reporting five new cases of MGCT, with a total of 21 tumors seen over a period of 25 years from 1967 to 1992.

Hepatobiliary rhabdomyosarcoma in children: diagnostic radiology.

Abstract Rhabdomyosarcoma (RMS) occurs infrequently in the liver and biliary tree. Although the radiological diagnosis may be simple when the tumour involves the extrahepatic bile ducts, no specific imaging features are known for hepatic RMS. We present four cases and discuss the role of diagnostic radiology in the management of this tumour.

Phase II study of pre-irradiation chemotherapy for childhood intracranial ependymoma. Children's Cancer Group protocol 9942: A report from the Children's Oncology Group†

Standard therapy for childhood intracranial ependymoma is maximal tumor resection followed by involved‐field irradiation. Although not used routinely, chemotherapy has produced objective responses in ependymoma, both at recurrence and in infants. Because the presence of residual tumor following surgery is consistently associated with inferior outcome, the potential impact of pre‐irradiation chemotherapy was investigated.

Kasabach-Merritt syndrome treated by therapeutic embolization with polyvinyl alcohol

The authors describe a 6 1/2-month-old boy with a large hemangioma involving the left buttock associated with a severe consumptive coagulopathy. Cosmetic improvement and resolution of the coagulation defect followed occlusion of the nutrient vessels to the hemangioma with polyvinyl alcohol. This is the first report of successful treatment of this condition with therapeutic embolization.