Stuart Toledano

The Miami pediatric quality of life questionnaire: parent scale.

Because there were limited measures available to assess health‐related quality of life (HRQL) in children with chronic illnesses, this study was initiated to develop an empirically derived questionnaire for use in evaluating HRQL issues in children treated for cancer. Extensive interviews were conducted with 30 families of children with cancer, 10 of pre‐school age, 10 of school age and 10 of adolescent age. Responses were videotaped and transcribed, then categorized to develop a pool of 56 items, which were administered to 132 children with cancer and to their parents. This report focuses on parental responses to objective items and ratings of importance of each of these items. Three primary categories, Self‐Competence, Emotional Stability and Social Competence, were identified, each of which had solid internal consistency, sensitivity and reliability across 1‐month intervals. The measure demonstrated the ability to discriminate between children with different types of cancer, offers an alternative to measures relying on expert judgment to assess HRQL and may lead to greater inclusion of psychological and social concerns as primary factors in determining HRQL in children participating in clinical trials. Int. J. Cancer Suppl. 12:11–17, 1999. ©1999 Wiley‐Liss, Inc.

Hematogenous brain metastasis in children

Hematogenous brain metastases are uncommon in childhood. Three patients and a literature review that includes centers reporting up to 36 years of experience are presented in this study. The total of 2,040 patients includes our three examples of one neuroblastoma, one hepatoblastoma, and one adrenal carcinoma. Cerebral hematogenous metastases were reported in 4.4% of 429 patients with neuroblastoma, 1.9% of 574 rhabdomyosarcoma patients, 6.5% of 386 patients with osteosarcoma, 3.3% of 487 Ewing sarcoma patients, 3.6% of 44 melanoma patients, 13.5% of 37 patients with germ cell tumors, and 1.3% of the 78 patients with Wilms tumor. Five miscellaneous patients included three with a hepatoblastoma and one each with adrenal carcinoma and nephroma. All of the large series reports have been published in oncology journals.

Treatment of recurrent eosinophilic granuloma with systemic therapy.

Purpose To describe the systemic treatment of recurrent eosinophilic granuloma. Methods Case report and review of Langerhans cell histiocytosis. Results A 9-year-old boy had painful, right upper eyelid swelling. A computed tomography scan showed a right superolateral orbital mass with evidence of bony erosion. Frozen section evaluation was consistent with eosinophilic granuloma. Biopsy and curettage were performed. Systemic work-up was negative for extraorbital disease. Recurrence of the orbital mass 6 weeks after surgery was confirmed by magnetic resonance imaging (MRI). Four weeks after treatment with prednisone and vinblastine, MRI showed a marked decrease in the size of the orbital lesion. Additional treatment with 6-mercaptopurine and methotrexate was initiated, and MRI 6 months later showed complete resolution of the lesion. Conclusions The treatment of recurrent eosinophilic granuloma is challenging. The goal is to effectively cure the lesion with minimal short-term and long-term side effects. Systemic steroids, vinca alkaloids, antimetabolites, and antifols are preferred because they have less toxicity and mutagenicity. Combination chemotherapy used in conjunction with treatment by a pediatric hematologist/oncologist appears to be an effective method of treating recurrent disease.

Idarubicin and cytosine arabinoside reinduction therapy for children with multiple recurrent or refractory acute lymphoblastic leukemia: a Pediatric Oncology Group study.

PURPOSE This study was designed to determine the toxicity of and response to idarubicin and cytosine arabinoside in children and adolescents with acute lymphoblastic leukemia (ALL) who had refractory or recurrent bone marrow disease. PATIENTS AND METHODS Patients <21 years of age with ALL in second or later bone marrow relapse or refractory to induction therapy were eligible. Some patients also had concurrent central nervous system (CNS) relapse. Therapy consisted of cytosine arabinoside, 1 g/m2/day given as a 6-h infusion, followed by bolus idarubicin, 5 mg/m2/day, both daily for 6 days. Children achieving remission received maintenance therapy with 3 days of etoposide, 100 mg/m2/day, followed by ifosfamide, 2.8 g/m2/day, alternating every 3 weeks with 3 days of cytosine arabinoside and idarubicin in the dosages described earlier. All courses of therapy were followed by granulocyte colony-stimulating factor (G-CSF). Removal from study to undergo bone marrow transplantation (BMT) was encouraged. RESULTS Eighty-two patients were entered. There were 14 deaths (nine early), mostly from documented or presumed bacterial or fungal sepsis. Overall, 30 patients achieved complete remission (37%). These were mostly of brief duration--only one patient was still alive at 600+ days after BMT. CONCLUSIONS Cytosine arabinoside and idarubicin showed moderate activity in heavily pretreated children with ALL.

Clinical trial of etoposide (VP-16) in children with recurrent malignant solid tumors

SummaryEtoposide (VP-16), 150 mg/M2, given intravenously daily for 3 days every 3 weeks resulted in 3 complete responses and 6 partial responses in 154 patients with a spectrum of recurrent malignant solid tumors. There was evidence of disease control in an additional 37 patients (27 mixed responses and 10 stable disease). These responses occurred primarily in patients with Ewings sarcoma, Hodgkins disease, neuroblastoma and rhabdomyosarcoma. Most of the patients had every extensive prior therapy; however prior therapy with teniposide (VM-26), the congener of VP-16, did not seem to preclude responses to the latter drug. Myelosuppression was the principal form of toxicity. Neutropenia characterized by absolute neutrophil counts of 0.5 to 0.9 × 109/L occurred in one-half of the patients, and thrombopenia with platelet counts of < 25 to 49 × 109/L in one-fourth. These results demonstrate a favorable therapeutic index for VP-16 in several recurrent childhood solid tumors, supporting its use as a component of primary therapy for these diseases.

Rhegmatogenous retinal detachment in retinoblastoma patients undergoing chemoreduction and cryotherapy.

PURPOSE To report the development of rhegmatogenous retinal detachment, with the retinal break adjacent to a cryotherapy scar, in three patients undergoing systemic chemotherapy for intraocular retinoblastoma. METHOD Case series. RESULTS Three patients with intraocular retinoblastoma were referred after poor response to systemic chemotherapy and local cryotherapy; three eyes of these three patients were noted to have rhegmatogenous retinal detachment and active retinoblastoma, with retinal breaks adjacent to cryotherapy scars. CONCLUSION Rhegmatogenous retinal detachment may result from retinal necrosis associated with cryotherapy in the setting of intraocular retinoblastoma treated with systemic chemotherapy and local cryotherapy.

Genital Rhabdomyosarcoma: Current Management and Review of the Literature

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and 20 per cent of these cancers involve the pelvis or genitourinary system. Radical pelvic surgery, such as exenteration, was considered at one time to be the standard treatment for this cancer which carried a very poor prognosis. Over the past 15 years, a combined modality approach to treating rhabdomyosarcoma, using chemotherapy, radiotherapy, and less radical surgery, has evolved and survival rates have improved. This paper presents a case of rhabdomyosarcoma involving the perineum which was treated by combination chemotherapy of Vincristine, Actinomycin-D, and Cytoxan, followed by wide local excision, interstitial and external beam radiotherapy, and postoperative chemotherapy. The literature on pelvic rhabdomyosarcoma is reviewed and the current approach to treating this cancer using multimodal therapy is discussed.

Congenital neutropenia: A case study

Infantile genetic agranulocytosis (IGA) has a high morbidity and mortality rate due to severe neutropenia. The pathogenetic mechanisms of this syndrome have not been elucidated. However, a recent clinical trial with recombinant human granulocyte-colony-stimulating factor (rhG-CSF) has shown a dramatic increase in the absolute neutrophil count in patients with IGA. This suggests that these patients have either a lack of granulocyte-colony-stimulating factor (G-CSF) or have a defect in the G-CSF receptors. A clinical trial of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) in an infant with IGA is reported in this article. A marked eosinophilic response was observed without any increase in the absolute neutrophil count (ANC). In an effort to elucidate the pathogenetic mechanism underlying IGA, we examined (a) the in vitro response of patients CFU-GM to rhGM-CSF and to rhG-CSF and (b) the ability of patients monocytes to produce G-CSF. Our results tend to support the thesis that the defect in IGA is at the G-CSF receptor level. We also found a lack of correlation between in vivo and in vitro response to rhGM-CSF

Aziridinylbenzoquinone (AZQ) in the treatment of recurrent pediatric brain and other malignant solid tumors - A Pediatric Oncology Group phase II study

SummaryTo assess the response rates and toxicity of AZQ in children with recurrent brain and other malignant solid tumors, a phase II study was implemented by the Pediatric Oncology Group. Eligible patients received AZQ 18 mg/M2/week i.v. for 4 doses followed by a 2 week rest period. Each dose was given over four hours (1/3 over the initial 20 minutes). After the first year, the dosage was reduced to 13 mg/M2 due to myelotoxicity resulting in treatment delays. No objective responses were observed in 73 evaluable children with various noncentral nervous system tumors. Of the 91 patients with brain tumors, there were 4 CRs and 2 PRs in patients with astrocytoma, ependymoma, glioblastoma multiforme, oligodendroglioma, brain stem glioma and intracranial yolk sac tumor (median duration, 10 months; range, 2–20+ months). Three of 4 CRs were achieved with a dosage of 18 mg/M2/week. An additional 13 children with brain tumors experienced stable or improved disease (duration, 2–36 + months; median 7.5 months). The principal toxicity was myelosuppression which was cumulative but there were also 3 allergic reactions to AZQ. We conclude that for selected brain tumors, the rates of objective response and stable disease plus the duration of responses support further assessment of AZQ in combination with other agents. Furthermore, the 18 mg/M2 dosage may provide better responses.

EVALUATION OF CHIP (IPROPLATIN) IN RECURRENT PEDIATRIC MALIGNANT SOLID TUMORS - A PHASE-II STUDY (PEDIATRIC ONCOLOGY GROUP)

CHIP (325 mg/M2), a second generation cisplatin derivative, was administered intravenously every 3 weeks to 85 pediatric patients with recurrent sarcomas (19), osteosarcomas (20), neuroblastoma (23), germ cell tumors (10), and other malignant tumors (7). Thirty-eight of them had been previously exposed to cisplatin. Partial remissions were only observed in 3 of 23 (13% SE=7%) patients having neuroblastoma. Severe thrombocytopenia (65%) and neutropenia (35%) were the dose limiting factors.