Jan Van Eys

Reviews: Special Nutritional Needs of Children with Malignancies: A Review

Nutrition support for the patient with cancer is an important part of the overall treatment regimen. Nutrition support for the child with cancer poses a special challenge. For the purpose of reviewing the special nutritional needs of children with cancer, a Task Force was formed by the American Academy of Pediatrics to review the current state of knowledge. The work of the Task Force was supported by the Food and Drug Administration through its Liaison Representative, Joginder Chopra, M.D., Staff support from the Academy was provided by Jean D. Lockhart, M.D., This review is prepared from the Task Force Report to the FDA. It is designed to review factors enhancing nutritional risks for the child with cancer and to discuss nutritional intervention strategies and their efficacies.

MOPP regimen as primary chemotherapy for brain tumors in infants

SummarySeventeen infants with central nervous system malignancies, all with tissue diagnosis, were treated with the combination chemotherapy nitrogen mustard, vincristine, procarbazine and a steroid (MOPP) as primary therapy following surgery. Diagnoses include: 7 astrocytomas (grade: 3-I, 3-II, 1-III), 6 medulloblastomas, 2 ependymoma/astrocytoma mixed, 1 ependymoma and 1 primitive neuroectodermal tumor. Fourteen were under 2 years of age, 2 between 2 and 3 years of age, and 1 between 3 and 4 years of age. Fifteen responded and 2 failed. Of the responders, 6 are in continuous complete remission (median duration 28.9+ months) and 9 are in relapse (median duration of remission 10.3 months). Of the 2 patients who failed and 9 who relapsed, 4 expired and 6 are living in partial or complete remission. We conclude that MOPP therapy is well tolerated, has effectiveness, and allows postponement of potentially debilitating radiotherapy in infants with brain tumors.

Cisplatin in recurrent pediatric brain tumors A pog phase II study a pediatric oncology group study

Forty‐six evaluable pediatric patients with primary recurrent brain tumors resistant to standard therapy were treated with cisplatin, 60 mg/m2/day, X2 days every 3 to 4 weeks, to study the efficacy and toxicity of this drug. Complete and partial responses, documented by computed tomography (CT) scan, were demonstrated in 4 of 10 patients with medulloblastoma and 3 of 15 patients with ependymoma. No activity was documented in astrocytic tumors. Dose limiting major toxicities were renal and auditory. It is recommended that the new analogues of cisplatin with less toxicity be studied in these tumors.

MOPP chemotherapy without irradiation as primary postsurgical therapy for brain tumors in infants and young children

Infants and young children who have brain tumors have a poor rateof survival and high treatment associated morbidity. A trial of mechlorethamine, vincristine (oncovin), procarbazine, and prednisone(MOPP) was performed to test the hypothesis that replacingradiotherapy with chemotherapy would improve survival and decreaselong term morbidity of infants who have brain tumors. Between 1976 and1988, 17 consecutive children less than 36 months old when diagnosed with medulloblastoma or ependymoma were treatedwith MOPP chemotherapy as primary therapy following surgical excision or biopsy of the tumor. Radiotherapy was reserved for recurrent disease. Ten of 17 children have survived without evidence of disease: medulloblastoma, eight of 12 with median survivaltime of 10.6 years (range, 6.2 to 15.2 yrs); and ependymoma, 2of 5 (at 13.0 and 16.0 yrs). Four of the 10 children with medulloblastomaand ependymoma who relapsed are now disease free at 7.5, 11.7, 12.2 and 13.5 yrs post relapse after receiving salvagetherapy with cisplatin (n = 1) or irradiation (n = 3). All relapsesoccurred within 26 months of diagnosis. Data on growth demonstrated heightless than the 5th percentile in all children who received cranial irradiation compared to 25 to 95th percentile for nonirradiated children. Intellectual ability for the groupwho did not require radiation was within normal range (mean IQ 100.1) and stable across annual assessments. Those who required radiation hadlower IQs which continued to decline over time (mean IQ 85 at mean age of 5.8 years, declining to 63 at 10 years).In young children with brain tumors, primary chemotherapy with MOPP, omitting radiotherapy, provides improved neurodevelopmental outcome and survival.

Intracranial ependymoma in children: analysis of prognostic factors

SummaryBetween 1955 and 1986, 25 children (aged 2 weeks to 15 years) were treated for intracranial ependymoma at M.D. Anderson Cancer Center. Nine patients had supratentorial primaries (5 high-grade, 4 low-grade), and 16 had infratentorial primaries (9 high-grade, 7 low-grade). Five patients had gross complete resection and 20 had incomplete resection. Seven patients received craniospinal irradiation (25–36 Gy to the neuroaxis, 45–55 Gy to tumor bed), 12 received local field irradiation (29–60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, and 6 children had postradiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses. Eight patients are alive, disease-free and without relapse from 1 year to 12 1/2 years from diagnosis (median 42 months). The primary failure pattern was local recurrence. The data suggest that 1) the long-term cure rate of children with ependymoma is suboptimal; 2) histologic grade may be of prognostic importance for supratentorial tumors; 3) prognosis appears worse for girls and infants under 3 years of age; 4) in well-staged patients routine spinal irradiation could be omitted; 5) the role of adjuvant chemotherapy is unclear.

Survival and neurologic outcome of infants with medulloblastoma treated with surgery and MOPP chemotherapy: a preliminary report

The results of treatment of infants with medulloblastoma using surgery and chemotherapy, without the use of radiation therapy, are reported. Both survival and outcome, in terms of growth, neurologic deficit, and intelligence are compared with the same parameters in children treated conventionally. Although preliminary, our results suggest that chemotherapy combined with surgery is a valid option for the treatment of infants with this type of neoplasm.

Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and Down's syndrome. A Pediatric Oncology Group study.

Of 2947 children with acute lymphocytic leukemia (ALL), treated during three consecutive studies of the Pediatric Oncology Group (1974–1986), 52 (1.8%) had Downs Syndrome (DS). Comparison of clinical and laboratory characteristics showed no significant differences in leukocyte count, racial distribution, sex ratio, platelet count, incidence of mediastinal mass, lymphadenopathy or hepatosplenomegaly, or percentage of blood or bone marrow blasts for children with ALL with or without Downs Syndrome (DS‐ALL or NDS‐ALL, respectively). However, children with DS‐ALL were slightly older at the time of presentation and had higher hemoglobin values. The relative frequency of each major immunophenotype (early pre‐B, pre‐B, T, or B) was also comparable for patients with or without DS. For this report, treatment regimens were categorized as either conventional (no consolidation therapy) or intensive. Cox regression analysis revealed that the presence of DS, a higher leukocyte count, black race, or age older than 10 years was independently associated with a poorer event‐free survival (EFS) for children treated with conventional chemotherapy. However, for the cohort of children who received intensive chemotherapy, DS was no longer an independent risk factor. In fact, event‐free survival (EFS) was markedly improved to a level comparable with that observed in the children diagnosed as having NDS‐ALL. On the other hand, serious toxicity, requiring interruption of treatment, was significantly more frequent in the intensively treated children with DS compared with similarly treated patients with NDS‐ALL, although deaths resulting from toxicity occurred infrequently.

Salvage chemotherapy for recurrent primary brain tumors in children

Sixty consecutive evaluable children with recurrent primary tumors of the central nervous system were treated with a regimen of vincristine, nitrogen mustard, procarbazine, and prednisone over a 12-year period. Tumor types included medulloblastoma (19), brain-stem glioma (16), astrocytoma (13), and a miscellaneous glioma (12). Responses and sustained survivals were achieved. Responses were highly dependent on tumor type. Disease progression was halted in 73% of the children with medulloblastoma, and three have survived in complete remission for more than 10 years from the start of therapy with vincristine, nitrogen mustard, procarbazine, and prednisone. Two of four patients with anaplastic glioma, are long-term survivors. In contrast, less than one third of children with brain-stem gliomas responded. Toxicity consisted mainly of neutropenia, thrombocytopenia, infections, and rarely a procarbazine rash.

Treatment intensity and outcome for children with acute lymphocytic leukemia of standard risk: a pediatric oncology group study

Four hundred thirty‐four children, with good‐risk acute lymphocytic leukemia (ALL), were assigned randomly to receive intensive or less intensive maintenance therapy with 6‐mercaptopurine and methotrexate, plus vincristine and prednisone pulses in such a way that patients on treatment 1 had their leukocyte counts maintained between 1500 and 3000/mm3. Patients on treatment 2 had leukocyte counts maintained between 3000 and 4500/mm3. Absolute granulocyte counts were maintained above 500/mm3 on both groups. All children received induction treatment with vincristine, prednisone and L‐asparaginase and had central nervous system (CNS) prophylaxis with cranial irradiation and intrathecal methotrexate. The overall remission rate was 94%. Event‐free survival at 8 years was 44% (SE, 5.6%). There was no significant difference in outcome between treatments 1 and 2 (P = 0.83). The incidence of infection was similar overall and not significantly different between treatment arms.

A comparison of two regimens for high‐risk acute lymphocytic leukemia in childhood. A pediatric oncology group study

Four hundred thirty patients with high‐risk acute lymphoid leukemia were entered on the acute leukemia in childhood protocol (AlinC 12) of the Pediatric Division of the Southwest Oncology Group (now the Pediatric Oncology Group) between 1976 and 1979. This study was a prospective randomized comparison of two regimens that had as their primary differences: (1) an intensification period with Cytoxan (cyclo‐phosphamide) and asparaginase after induction; (2) a period of intravenous methotrexate before initiating maintenance; and (3) in the regimen that had those two additions, triple‐drug chemoprophylaxis of the central nervous system (CNS) using methotrexate, hydrocortisone, and cytosine arabinoside as compared to cranial irradiation and intrathecal methotrexate. All patients received vincristine and prednisone induction, 6‐mercaptopurine and methotrexate maintenance, and vincristine and prednisone pulse intensification. There was no significant difference in the rate of bone marrow relapse. However, overall disease‐free survival favored the arm with intensification and chemoprophylaxis because of a lesser incidence of extramedullary relapse. Thus, for treatment 1 versus treatment 3 the two‐sided P values were for overall disease‐free survival 0.16; bone marrow relapses 0.13; all CNS relapses 0.04; and all extramedullary disease relapses 0.013. It is concluded that intensification as delivered in this protocol protects against testicular relapse and that chemoprophylaxis is adequate prophylaxis against isolated CNS relapse.