Surgical resection alone is effective treatment for ovarian immature teratoma in children and adolescents: a report of the pediatric oncology group and the children's cancer group.

OBJECTIVE: In both adult women and children the potential for malignant recurrence from ovarian immature teratoma has prompted the standard use of chemotherapy after complete resection of the primary tumor. The efficacy of postoperative chemotherapy in children and adolescents with ovarian immature teratoma, however, has not been established. A pediatric intergroup trial (INT 0106) was designed to determine the need for postoperative chemotherapy in patients with ovarian immature teratoma after management with surgical resection only. STUDY DESIGN: Between 1990 and 1995, 44 patients with completely resected ovarian immature tumor and without postoperative chemotherapy, who were able to undergo assessment, were accrued. Tumor tissue was evaluated by central pathology review to confirm diagnosis and determine tumor grading of immature neural elements. Patients were followed carefully for recurrence of disease with appropriate diagnostic imaging and serum marker studies. RESULTS: Thirty-one patients had pure ovarian immature teratoma with a tumor grade of 1 (n = 17), 2 (n = 12), or 3 (n = 2). Age at diagnosis ranged between 1.5 and 15 years (median, 10). Of the 29 patients studied, the serum alpha-fetoprotein level was elevated in 10 (34%); the median level was 25 ng/ml. Thirteen patients had ovarian immature teratoma plus microscopic foci of yolk sac tumor. Tumor grade was 1, 2, or 3 in 1, 6, and 6 patients, respectively. Age ranged between 6 and 20 years (median, 12). In the 12 patients evaluated for serum alpha-fetoprotein, 10 (83%) had elevated levels; the median level was 262 ng/ml. The 4-year event-free and overall survival for the ovarian immature teratoma group and for the ovarian immature teratoma plus yolk sac tumor group was 97.7% (95% confidence interval, 84.9%-99.7%) and 100%, respectively. The only yolk sac tumor relapse occurred in a child with ovarian immature teratoma and yolk sac tumor who was then treated with chemotherapy and is alive and free of disease 57 months after recurrence. CONCLUSION: The results of this study suggest that surgery alone is curative for most children and adolescents with resected ovarian immature teratoma of any grade, even when elevated levels of serum alpha-fetoprotein or microscopic foci of yolk sac tumor are present. This experience strongly supports avoiding the long-term effects of chemotherapy in most children with ovarian immature teratoma by reserving postoperative therapy for cases with relapse.

Assessment of ventricular function in infants and children. Response to dobutamine infusion.

A method to assess ventricular functional reserve in infants and children unable to perform dynamic exercise was evaluated. Left ventricular ejection fraction was measured by radionuclide angiocardiography at rest and during infusion of dobutamine in 5-15 micrograms/kg/min dosages. The only side effects noted were arrhythmias in two patients, who had similar ectopy documented previously. Group left ventricular ejection fraction increased from 0.40 +/- 0.21 to a maximum of 0.49 +/- 0.24 (P less than 0.001). Left ventricular ejection fraction at 5 micrograms/kg/min (0.44 +/- 0.23) was not statistically different from that measured during infusion of dobutamine at 10 micrograms/kg/min (0.48 +/- 0.24). The six patients receiving anthracyclines, who had relatively low function at rest and increased function during dobutamine administration, were continued on their anticancer regimen without deteriorating in condition. Absolute values of left ventricular ejection fraction correlated best with the prognosis in patients with idiopathic dilated cardiomyopathy or structural abnormalities; six out of ten patients whose left ventricular ejection fraction never rose above 0.40 have either died or are in transplant protocols. Thus, study of left ventricular function can be performed easily during dobutamine infusion, generating valuable prognostic information.

Effectiveness of two methods of parenteral nutrition support in improving muscle mass of children with neuroblastoma or Wilms' tumor. A randomized study.

The short-term and long-term effectiveness of central parenteral nutrition (CPN) versus peripheral parenteral nutrition (PPN) in improving muscle mass (arm muscle area [AMA]) was evaluated for 24 malnourished children with newly diagnosed Stage IV neuroblastoma (n = 14) or Stages II-V Wilms' tumor (n = 10). Patients were randomized to either CPN or PPN plus enteral nutrition (EN: intense nutrition counseling, oral foods, and supplements) for 4 weeks followed by EN until week 10. Oncologic treatment was similar for each tumor type. Dietary, anthropometric, and biochemical measurements were obtained at weeks 0, 4, and 10. During weeks 1 through 4, energy (CPN: means 100 +/- 4; PPN: means 96 +/- 4% of healthy children) and protein (CPN: means 2.5 +/- 0.1; PPN means 2.7 +/- 0.2 g/kg) intakes of the two groups did not differ. The AMA increased (P less than 0.05) with 4 weeks of CPN but not with PPN; changes thereafter with EN were not significant. Weight (P less than 0.05) and triceps skinfolds (P less than 0.01) increased with 4 weeks of PN in both groups and decreased with EN thereafter (P less than 0.01) but were higher at week 10 than diagnosis. Increases in albumin in both groups reached significance at week 10 (P less than 0.05). These data show that CPN improves AMA in malnourished children with neuroblastoma or Wilms' tumor when energy and protein intakes are adequate. The AMA gains can be maintained thereafter with EN.

Integration of nutrition support into oncologic treatment protocols for high and low nutritional risk children with Wilms' tumor. A prospective randomized study.

Benefits and risks of nutrition support were evaluated in 31 malnourished children with newly diagnosed Wilms' tumor managed according to the third National Wilms' Tumor Study protocol. Patients were classified at diagnosis as being at high nutritional risk (HNR, n = 19) or low nutritional risk (LNR, n = 12). Ten HNR patients were randomized to central parenteral nutrition (CPN) and nine HNR patients were randomized to peripheral parenteral nutrition (PPN) plus enteral nutrition (EN) for 4 weeks of initial intense treatment and EN (nutritional counseling, oral foods and supplements) thereafter. Thirteen HNR patients (seven CPN, six PPN) completed the protocol. Twelve LNR patients received EN; 11 Stage I malnourished patients were randomized to 10 or 26 weeks of chemotherapy. Dietary, anthropometric, and biochemical data were determined for HNR patients at weeks 0-4, 6, 13, 19, and 26 and for LNR patients at weeks 1, 2, 5, and 26. In HNR patients, adequate parenteral nutrition support reversed protein energy malnutrition (PEM), and prevented chemotherapy and radiotherapy delays due to granulocytopenia. CPN was superior to PPN in reversing PEM: energy intake, weight gain, and retinol binding protein were higher (P less than 0.05). LNR patients lost weight and fat reserves in the first 2 weeks of treatment; depletion persisted at week 5, and 25% had chemotherapy delays. Thereafter, EN reversed PEM in patients with both chemotherapy regimens. These data suggest that CPN is preferable during initial intense treatment for HNR patients, and that, although EN is ineffective in preventing depletion and treatment delays in the first 5 weeks of treatment for LNR patients, it is effective thereafter.

The relationship of various aspects of surgical management to outcome in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group.

Recently, much attention has been focused on the role of adjuvant chemotherapy in the treatment of osteosarcoma. Surgery, however, remains the primary modality for the ablation of this disease. In this report, we examine the relationship of various aspects of surgical management of osteosarcoma to prognosis for disease-free survival (DFS) in a randomized study of 234 pediatric patients. Attention is restricted to 166 patients with nonmetastatic disease confined to an extremity and who were randomized to receive one of two chemotherapeutic regimens. No advantage with respect to DFS was attributable to the various aspects of surgical management considered: interval from first symptoms to definitive surgery, surgical sequence, and type of surgery. Only two local recurrences were seen. One occurred in an above knee amputation stump and the other occurred in a patient receiving a tibial allograft. One of these patients died of pulmonary metastases within 6 months of recurrence; the other patient is alive without evidence of disease at last contact after resection of the recurrence followed by chemotherapy.

Nutritional support of children with neoplastic diseases.

There are numerous factors promoting the development of PEM in the child with cancer. Some of these factors are related to the tumor, many to the treatment itself, and some to failure of recognition of PEM. Not all children with cancer are at great risk for the development of PEM. These patients must be monitored and supported with comprehensive enteral programs. Children who have developed or are at risk for PEM must be identified and supported with CPN or PPN plus CEN during early intensive periods of treatment and during the later phases of abdominal radiotherapy, operative resection of tumor, or relapse. The decision to institute CPN must be based not only on the child's current nutritional status but also on the nature of the therapy he or she is soon to receive and the likelihood that he or she will be able to maintain an adequate intake during that therapy. Realistic goals must be set for nutritional support. The value of nutritional intervention lies in its ability to correct or prevent the development of adverse effects related to PEM. This support is hoped to contribute to improved tolerance of therapy, increased energy to complete normal day-to-day activities, and an improved sense of well-being for the child. If these goals have been accomplished, then the nutritional therapy has been successful.

The value of nutrition support in children with cancer.

A positive stance towards nutrition support of the child with cancer assures potential for normal growth, development, and quality of life during extended oncologic treatment. Data from recent studies of children with cancer (advanced neuroblastoma, Wilms' tumor) demonstrate the importance of integrating nutrition staging, assessment, and support into treatment protocols. Patients with solid tumors and lymphomas who are malnourished at diagnosis have a poor outcome when compared to nourished counterparts. Enteral nutrition (intensive nutrition counseling and favorite, nutritious foods) is effective in low nutritional risk groups but ineffective in preventing or reversing protein-energy malnutrition in high nutritional risk groups. For high-risk groups, central parenteral nutrition is a relatively short-term, but important, support measure which allows children to grow despite extended periods of intense oncologic treatment. The patient's nutritional course may affect bone marrow suppression and the ability to tolerate aggressive chemotherapeutic treatment. Although treatment tolerance may be improved with nutrition support, adequacy of primary oncologic treatment outweighs other supportive factors as a determinant of ultimate survival.

Efficacy of magnetic resonance imaging in 139 children with tumors.

One hundred thirty-nine children with neoplasms were studied using magnetic resonance imaging (MRI). This procedure was as accurate as computed tomography in predicting tumor histology, except that MRI was unable to detect small areas of tumor calcification. Magnetic resonance imaging could accurately identify the organ of origin of tumor masses and differentiate soft tissue from fat, fluid, or hemorrhage. In addition, MRI was helpful in planning surgery in many cases: It was better than computed tomography in defining the size and extent of soft-tissue tumor masses. It was accurate in defining the extent of the spread of bone sarcomas in the bone marrow. Without requiring the injection of intravenous contrast agents, it accurately defined displacement, encasement, or invasion of major abdominal blood vessels by Wilms' tumors and neuroblastomas. As a means of evaluating pediatric neoplasms, MRI is noninvasive, painless, and well tolerated by children, and it uses no radiation.

Congenital monoblastic leukemia cutis. A case report with chromosomal abnormality: del (10p).

Congenital monoblastic leukemia cutis is a rare disorder. We report an infant who developed infiltrative skin lesions by 2 weeks of age, which, when biopsied at 4 1/2 months of age revealed a monoblastic infiltrate. Blasts in the peripheral blood were not seen until 1 week before her death at 8 months of age. Chromosomal analyses of her bone marrow showed an abnormal clone of cells with a 46,XX,del(10)(p12) karyotype. Although chromosome 10 is rarely involved in hematologic malignancies, abnormalities of this chromosome within the region 10p11-10p13 have now been shown in four of 10 reported cases of congenital monoblastic leukemia.

Short- and long-term effectiveness of enteral and parenteral nutrition in reversing or preventing protein-energy malnutrition in advanced neuroblastoma. A prospective randomized study.

The effectiveness of enteral and parenteral nutrition regimens in preventing or reversing protein-energy malnutrition (PEM) and in preventing treatment delays was evaluated in 32 children receiving treatment for newly diagnosed Stage III (3 patients) and IV (29 patients) neuroblastoma. Ten of 18 malnourished patients were randomized to central parenteral nutrition (CPN) and 8 to peripheral parenteral nutrition (PPN) plus enteral nutrition for 4 weeks and then received enteral nutrition (EN: intense nutrition counselling, oral foods and supplements) for weeks 5 through 10. Ten of 14 nourished patients received EN and 4 CPN for 4 weeks and EN thereafter. Dietary, anthropometric and biochemical measurements were determined for weeks 0, 1, 2, 3, 4, 7, and 10 for 24 patients who completed the protocols. In malnourished patients, both CPN (seven patients) and PPN (seven patients) were effective in reversing PEM in the first 4 weeks; thereafter, EN effectively maintained nutritional gains in both groups. In nourished patients, EN (seven patients) was not as effective as CPN (three patients) in preventing PEM during the first 4 weeks; afterwards, EN maintained gains in the CPN group but did not promote needed increases in weight nor fat reserves in the EN group. Patients supported by parenteral nutrition (PN, weeks 1-4) had fewer treatment delays (2/17, 12%) than EN patients (4/7, 57%, P less than 0.05). These data indicate that PN reverses or prevents PEM and prevents treatment delays during the first 4 weeks of intense oncologic treatment and provides nutritional benefits which can be maintained with EN thereafter.

Chemotherapy-associated Raynaud's phenomenon in a two-year-old girl.

Raynaud's phenomenon occurred in a 2-year-old girl 17 months after starting multiagent chemotherapy for an endodermal sinus tumor of the vagina. Symptoms began 2 months after receiving her final dose of bleomycin, and gradually resolved over a 6-month period despite continuing vinblastine. Chemotherapy-associated Raynaud's phenomenon appears to be unusual in young children, although mild episodes of vasospasm may not be reported by children or their parents. Specific questions regarding symptoms of Raynaud's phenomenon should be asked of all children receiving vinblastine and bleomycin therapy.

Magnetic resonance imaging of bone marrow disease in children.

Seven children underwent magnetic resonance imaging (MRI) of the bone marrow: results showed that it is technically feasible to obtain good MR images of marrow in children. MR has detected abnormality in the bone marrow of a child who had metastatic neuroblastoma. The extent of abnormality in the femur correlated well with findings of a bone marrow isotope scan. In one child who had idiopathic aplastic anemia, diseased marrow could not be distinguished from normal marrow on MR images. MRI identified abnormality of the marrow in osteogenic sarcoma, and demonstrated change in response to chemotherapy. It displayed marrow spread of tumor as well as CT. MRI showed marrow abnormality in four children who had leukemia.

Effectiveness of central parenteral nutrition versus peripheral parenteral nutrition plus enteral nutrition in reversing protein-energy malnutrition in children with advanced neuroblastoma and Wilms' tumor: a prospective randomized study.

The effectiveness of central parenteral nutrition (CPN) versus peripheral parenteral nutrition (PPN) plus enteral nutrition in reversing protein-energy malnutrition was evaluated in 19 children (nine CPN, 10 PPN) with advanced neuroblastoma or Wilms' tumor. Weekly dietary, anthropometric, and biochemical measurements were compared for 15 patients (eight CPN, seven PPN) who completed more than 25 days of nutrition support. The groups had similar mean energy and protein intakes (CPN: 95 +/- 5% of healthy children, 2.5 +/- 0.3 g/kg; PPN: 102 +/- 5% of healthy children, 2.9 +/- 0.3 g/kg). Increases in weight (p less than 0.001), subscapular skinfold thickness (p less than 0.001), albumin (p less than 0.05), and transferrin (p less than 0.05) for the first 28 days were significant and did not differ between groups. Fever, sepsis, elevated SGOT, and severe anemia occurred with both CPN and PPN. PPN resulted in subcutaneous infiltrations and more psychological trauma. PPN with enteral nutrition seems most appropriate for short term intravenous nutrition support or as a temporary substitute for CPN; CPN is preferred for long-term support.

Effect of nutrition staging on treatment delays and outcome in Stage IV neuroblastoma.

The effect of the state of nutrition of 18 children with Stage IV neuroblastoma at diagnosis and during initial therapy, was evaluated with respect to treatment delays, drug dosage alterations, tumor response, days to first event (relapse or death), and survival. All patients received similar therapy (CCSG protocol CCG 371). Based on nutrition staging at diagnosis, nine were classified as malnourished; four were randomized to receive total parenteral nutrition (TPN) and four peripheral parenteral nutrition plus enteral nutrition for 28 days (through 2 chemotherapy courses), and one died before randomization. Nine were nourished at diagnosis; seven received a comprehensive enteral nutrition program and two received TPN. By life-table analysis, the duration of remission was significantly greater in the nourished than the malnourished (P less than 0.01) and a trend towards improved survival was evident at one year (P = 0.08). The median length of survival for children nourished at diagnosis was approximately 12 months, whereas those malnourished had a median survival of only 5 months. Nine children remained nourished or were becoming renourished during the first 21 days of therapy, and one of these had treatment delays and decreased drug dosages. Seven were becoming malnourished or remained malnourished during this period and six had treatment delays (P less than 0.01). These data support the idea that nutrition staging at diagnosis and during initial treatment should be an integral part of protocol design and initial evaluation of children with Stage IV neuroblastoma.

Invasive aspergillosis of paranasal tissues in children with malignancies.

Paranasal aspergillosis was encountered in five children with relapsed malignancies. All had received broad-spectrum antibiotics within two weeks of development of aspergillosis, and all had absolute granulocyte counts less than 200/mm3 for at least three weeks. None had received prior antifungal therapy. There was an average delay of eight days before the correct diagnosis was established by either biopsy or culture. These data emphasize the need to obtain surveillance cultures of the upper respiratory tract passages in severely neutropenic patients receiving prolonged antibiotic therapy, and raise a question concerning prophylactic use of antifungal therapy in this group.

Rhabdomyosarcoma in childhood: analysis of survival in 98 cases.

Ninety-eight infants and children with rhabdomyosarcoma were analyzed for age, stage, site, and therapy as they relate to survival. Age and sex were not factors. Survival was 91% (10/11) for Stage I, 86% (13/15) for Stage II, 35% (12/34) for Stage III, and 5.2% (2/38) for Stage IV. Overall survival was 37% (37/98); however, 75% had advanced disease at diagnosis. Primary tumor site was genitourinary (GU) (31), extremity (17), head-neck (14), trunk (14), orbit (8), paratesticular (4), retroperitoneal (3), paraspinal (3), buttocks (3), and perianal (1). Survival was favorable in orbital, paratesticular, and (GU) sites. Survival was 20% (9/45) before and 52% (28/53) after chemotherapy and irradiation. The only survivors had embryonal cell histology. Tumor stage and site are important prognostic indicators. Chemotherapy improves survival in Stage I (91%) and Stage II (86%) and shrinks bulky Stage III tumors allowing less radical procedures in selected sites (e.g., GU). Survival is poor in Stage III (35%) and dismal in Stage IV (5.2%) despite combined therapy. Relapse was fatal despite attempts at second-look resection, and altered chemotherapy and irradiation.