Donald G. Norris

Treatment of children with progressive or recurrent brain tumors with carboplatin or iproplatin: a Pediatric Oncology Group randomized phase II study.

PURPOSE The Pediatric Oncology Group (POG) conducted a randomized phase II study to evaluate the activity of carboplatin and iproplatin in children with progressive or recurrent brain tumors. PATIENTS AND METHODS The study was designed to evaluate the activity of these agents and to compare the toxicities associated with their use. Treatment consisted of carboplatin 560 mg/m2 at 4-week intervals or iproplatin 270 mg/m2 at 3-week intervals. RESULTS The major toxicity observed was myelosuppression, particularly thrombocytopenia, for both agents. Ototoxicity (grade 1 or 2) was seen in 2.5% of patients treated with carboplatin and 1.3% of patients treated with iproplatin. The majority of patients with low-grade astrocytic neoplasms treated with carboplatin (nine of 12 patients) or iproplatin (eight of 12 patients) demonstrated tumor response or prolonged stable disease that persisted off-therapy. The duration of stable disease produced by carboplatin was particularly striking, ranging from 2 months to 68 + months (median, 40 + months). Neither drug demonstrated appreciable activity in the treatment of medulloblastoma (two of 26 responses to carboplatin, one of 14 responses to iproplatin), ependymoma (two of 17 responses to carboplatin, none of seven responses to iproplatin), high-grade glioma (two of 19 responses to carboplatin, one of 14 responses to iproplatin), or brain-stem tumors (one of 23 responses to carboplatin, none of 14 responses to iproplatin). CONCLUSION Carboplatin is active against low-grade gliomas. Further evaluation of the role of carboplatin in the preirradiation treatment of children with low-grade gliomas of the optic pathway is currently underway in a clinical trial.

The Spectrum of Eosinophilic Gastroenteritis Report of Six Pediatric Cases and Review of the Literature

Eosinophilic gastroenteritis is an inflammatory disease of unknown etiology characterized by infiltration of the gastrointestinal tract with eosinophilic leukocytes, accompanied by varying abdominal symptoms and usually by peripheral blood eosinophilia. We report our experience with six pediatric cases presenting to the Cleveland Clinic Foundation over the past eight years. Unusual findings in our patients included ascitic fluid without eosinophilia and eosinophilic pericarditis (one patient), and eosinophilic cholecystitis (one patient). Endoscopic examination and biopsy helped to establish the diagnosis in all patients. Bone marrow aspiration supported the diagnosis by demonstrating eosinophilia and identifying reactivation of the disease, even in cases without peripheral eosinophilia. All six patients responded promptly to prednisone. Diagnosis is challenging and eosinophilic gastroenteritis may be more common than is recognized. This series of cases significantly expands the spectrum of the disease in children, and documents the usefulness of diagnostic endoscopy in this condition.

Criteria and definitions for response and relapse in children with brain tumors

Traditional criteria and definitions for response and relapse are not completely suitable for children with brain tumors. Response and relapse for brain tumors need to be defined using the most objective criteria available, that is, the computed tomography (CT) scan findings. Relapse may also be defined by myelography, cerebrospinal fluid analysis, or biopsy of extraneural disease. Standardization of response and relapse will lead to meaningful comparisons of patients treated with various therapies. Cancer 56: 1824‐1826, 1985.

Periosteal Ewing's sarcoma

Ewings sarcoma is a small cell malignant tumor that usually arises in the medullary cavity of bone. Less frequently, it originates in soft tissue and may secondarily invade underlying bone. The origin of Ewings sarcoma in a periosteal location without extension into either the bone or adjacent soft tissue has not been clearly documented. Other malignant tumors of bone (e.g., osteosarcoma) appear to have a somewhat better prognosis when confined between periosteum and bone. The case of a patient with a periosteal Ewings sarcoma who received a radical excision and postoperative chemotherapy and who is without evidence of disease with over 2 years follow‐up is reported.

Pretransplant chemotherapy in pediatric hepatocellular carcinoma

The prognosis for pediatric patients with hepatocellular carcinoma is poor, except for fewer than half the patients, who can be rendered disease-free with conventional liver resection. Multicentric, bilobar liver cancer remains unresectable, even after radiation and chemotherapy. Liver transplantation alone for primary hepatic cancer has had limited success. Chemotherapy has been reserved for use after transplantation, with little demonstrable benefit. A pilot program of pretransplant chemotherapy was undertaken. Four adolescent patients with unresectable, multicentric, bilobar hepatocellular carcinoma were staged noninvasively, underwent chemotherapy followed by a final staging laparotomy, and then had liver transplantation. Three of the four patients survived and have no evidence of recurrence 84, 67, and 47 months after diagnosis and 76, 65, and 44 months after transplantation. Pretransplant chemotherapy has four potential advantages: (1) minimized risk of posttransplant opportunistic infections, (2) less tumor bulk at the time of transplantation, (3) fewer local recurrences, and (4) a lower rate of metastasis.

Noninvasive Testicular Screening in Childhood Leukemia

To evaluate the potential of transscrotal ultrasound and magnetic resonance imaging as noninvasive screening methods we studied 8 boys with acute lymphocytic leukemia before testicular biopsy. Ultrasonic images of the testes were performed in 4 patients, including 2 with negative and 2 with positive biopsies, and all images were interpreted as normal. Magnetic resonance images of the testes also were interpreted as normal in 4 patients, including 2 with negative and 2 with positive biopsies, and they were technically inadequate in the remaining 4. The results suggest that neither transscrotal ultrasonography nor magnetic resonance imaging as currently applied may substitute reliably for testicular biopsy as a screen for occult testicular leukemia.

RENAL SARCOMAS OF CHILDHOOD

Renal sarcomas in infants and children are extremely uncommon. Previously classified as Wilms tumors with unfavorable histology, these tumors were thought to be variants of Wilms tumors but in general have a worse prognosis. Our recent experience with 4 cases of renal sarcomas indicate that these tumors must be approached individually and treated appropriately. Their histologic picture and their varying response to surgery and chemotherapy suggest that these unusual tumors are not variants of Wilms tumors but instead sarcomas unrelated to the classic Wilms tumors.