Showing papers in "Medical and Pediatric Oncology in 1998"

Teratomas in infancy and childhood

Abstract: Background and Procedure. Outcomes in children with teratomas collected between October 1982 and December 1995 in cooperative protocols of the German Society of Pediatric Oncology and Hematology (GPOH) were analyzed. Teratomas were diagnosed in 329 (42%) of 780 registered patients with germ cell tumors. The annual incidence was 0.24/100,000. Main primary sites were coccygeal (n = 132, 2.2:1 female predominance), ovary (n = 81), testis (n = 40) and brain (n = 15, 2.8:1 male predominance). Results. Two hundred seventy cases of extracranial non-testicular teratoma were evaluated : In mature teratomas (n = 154) the observed relapse rate was 10%. Incomplete resection was the main risk factor for relapse. After complete resection, the relapse-free survival (RFS, Kaplan-Meier-estimation) was 0.96 ± 0.01 In = 126, observation time 18-155 months) in comparison to an RFS of 0.56 ± 0.09 in incompletely resected teratomas grade 0 (n = 28, observation time 28-94 months) (P< 0.01). Im-mature teratomas were treated by surgery alone in 76 cases and by surgery and adjuvant chemotherapy in 40 cases. The observed relapse risk was 18%. Main risk factors for relapse were incomplete tumor resection (n = 38) as well as immaturity in incompletely resected teratomas. Fifteen of 29 relapsing patients presented with malignant tissue in the recurrent tumor (mainly yolk sac tumor); in contrast, seven of 40 patients with immature teratoma relapsed despite adjuvant chemotherapy without showing malignant components (P = 0.014). Nine of 36 (25%) relapsing patients died of disease. Eleven of the 27 (41%) surviving children suffered from mutilation after repeated surgery. Comments. It is suggested that an international randomized trial for patients with incompletely resected high risk teratoma be initiated to evaluate the effect of adjuvant chemotherapy on specific end-points: 1) influence on relapse rate in general; 2) reduction of the proportion of malignant relapses; 3) avoidance of mutilating surgery.

Intracranial ependymomas in children: A critical review of prognostic factors and a plea for cooperation

Abstract: Background Current controversies in pediatric intracranial ependymoma include histologic categorization and management Most of our knowledge of this disease comes from single-institution reports Methods A literature search was done, covering the period 1976–1996 The aim of this review is to analyze the prognostic factors reported in the literature over the last 20 years Results Forty-five series were reviewed, including more than 1,400 children The largest series reported on 92 patients, and the accrual rate ranged from 032–12 patients per year None of the prognostic factors reported achieved a consensus throughout the different series Histology remains a major issue, and the range in the incidence of anaplastic ependymo mas (7–89%) highlights the difficulty in agreeing on a histological grading system The role of surgery on the outcome seems to be determinant Recent series based on homogeneous imaging-documented extents of resection strongly support the benefit of postoperative radiotherapy The lack of a proven, effective chemotherapy regimen precludes its use except in prospective pilot studies Conclusions Limited information is available from single-institution reports in ependymoma Only large national or international studies can provide enough information to allow a multivariate analysis of the prognostic factors, and thus lead to new therapeutic proposals Med Pediatr Oncol 30:319–331, 1998 © 1998 Wiley-Liss, Inc

Long‐term gross motor performance following treatment for acute lymphoblastic leukemia

Abstract: Background The primary purpose of this descriptive study was to determine the long-term effects of cancer treatment in childhood on musculoskeletal function and gross motor skills. Procedure. Musculoskeletal and gross motor function were assessed in a cohort of 36 survivors of acute lymphoblastic leukemia (ALL) seen in a pediatric tertiary care referral centre, compared to 36 age and gender matched comparison subjects. Basic gross motor skills were assessed using dimensions D: standing, and E: walking, running, and jumping of the Gross Motor Function Measure (GMFM). Strength, balance, and running speed and agility were assessed using the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP). Hand grip strength and ankle dorsiflexion range of motion were also measured. Findings in the children with ALL were compared by dependent (paired) t-tests to those in age and gender matched children. Results. The GMFM scores for standing were 98.7% and for walking, running, and jumping were 99% of normal. The mean standard scores for the BOTMP were significantly lower than those of the comparison group: strength 11.5 vs. 19.4, balance 9.4 vs. 15.5, and running speed and agility 9.9 vs. 16.6. The ALL subjects had less hand grip strength 156.3 vs. 190.2, and less ankle dorsiflexion 7.5 vs. 16.1° than the comparison group. The survivors of childhood leukemia were able to perform most basic gross motor functions. However, musculoskeletal impairment was evident and levels of motor proficiency were significantly poorer than those of age and gender matched children. Conclusions. Programs to promote physical activity and limit disability may improve gross motor function and increase overall quality-of-life in survivors of leukemia in childhood. Med. Pediatr. Oncol. 31:86–90, 1998. © 1998 Wiley-Liss, Inc.

Renal-cell carcinoma in children: a different disorder from its adult counterpart?

Abstract: Background Renal-cell carcinoma (RCC) is a rare tumor in children. To address whether RCC in children differs from its adult counterpart, we report a series of 16 children with RCC (5 boys, 11 girls, mean age 9.6 years, range 3–19 years) presenting between 1979 and 1996 at three pediatric centers. Procedure. Pathology showed papillary RCC in five patients (31%). Nonpapillary tumors were present in 11 (69%), of which nine were clear-cell type (56%), one was chromophobe-cell type (6%), and one was granular-cell type (6%). Cytogenetic studies were performed on four. Results. In two tumors, normal karyotypes (45,XX or 45,XY) were found. In another, there were translocations: t(X;1), t(X;2), and t(6;14). In the fourth, analysis revealed 46,XX/46,X,t(X;17)(p11.2;q25),t(1;12). Several features in this series differ from those reported in adults. In adults, RCC is more frequent in males, is usually nonpapillary, and is characterized cytogenetically by deletions or rearrangements in the short arm of chromosome 3. In contrast, in our series there was no male predominance and a higher proportion of papillary tumors. In addition, two of four cytogenetically analyzed tumors had translocations involving the X chromosome. Translocations involving the Xp11.2 locus have been infrequently reported in both adults and children with papillary RCC. Conclusions. The higher frequency of papillary histology and the presence of translocations involving Xp.11.2 in two cases raise the possibility of a unique subtype of RCC in children. Med. Pediatr. Oncol. 31:153–158, 1998. © 1998 Wiley-Liss, Inc.

Treatment of lymphoid malignancies in patients with ataxia‐telangiectasia

Abstract: Background Patients with ataxia-telangiectasia (A-T) are at an increased risk for developing lymphoid malignancies, yet the appropriate therapy remains unknown. Radiation therapy at conventional doses results in destruction of normal tissue, which has suggested that full-dose chemotherapy might result in unacceptable toxicity in A-T patients with cancer. Procedure The medical records of 412 A-T patients were reviewed to identify those patients who developed lymphoid malignancies and to analyze the type and duration of therapy, events during therapy, and off-therapy follow-up. Results Of 74 A-T patients with lymphoid malignancies, 32 patients received chemotherapy. The 21 patients treated with standard chemotherapy had a significantly better median survival (9 months, range, 1–162+ months vs. 5 months, range, 0.5–28 months) (P= 0.03) and complete remission rate (76% vs. 9%) (P = 0.001) than the 11 treated with reduced dose chemotherapy. Three of the 21 full-dose chemotherapy patients required dose reductions because of neutropenia. Seven of the 14 patients exposed to 1,200 mg/m2 or greater of cyclophosphamide developed hemorrhagic cystitis. All three patients exposed to bleomycin developed pulmonary disease which was fatal in two. Of the 16 standard-dose chemotherapy patients who achieved a complete remission, two remain disease-free, five have died of recurrent disease, and five died of pulmonary disorders and four of other causes while in remission. Conclusions Standard-dose chemotherapy should be given to each A-T patient with a lymphoid malignancy unless additional physical or emotional problems make it unlikely that the patient will benefit. Morbidity and mortality may be reduced by prophylaxis against hemorrhagic cystitis and early detection and treatment of pulmonary disorders. Med. Pediatr. Oncol. 31:491–497, 1998. © 1998 Wiley-Liss, Inc.

Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study.

Abstract: Background The objectives of this study were to compare vincristine/actinomycin D/cyclophosphamide/adriamycin (VACA) with VACA plus imidazole carboxamide (DTIC) (VACAD) therapy in regards to complete/partial response and event free survival rates in children and adolescents with metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) or previously chemotherapy-naive recurrent NRSTS or locally persistent gross residual tumor after surgery and radiation therapy. Procedures Between 1986 and March 1994, 75 patients entered this randomized study comparing VACA and VACAD, given at 3 week intervals. Sixty-one patients were considered eligible and received chemotherapy and radiation therapy to the primary tumor and areas of metastases. Thirty-six patients had regional unresected (Group III) disease, and 25 had metastatic disease (Group IV) at time of accession. Thirty-six patients received VACA(11 were not randomized), and 25 received VACAD. Results With a median follow-up of greater than 4 years, overall and event-free survival for all eligible patients are 30.6% and 18.4%, respectively (S.E: 9.5% and 6.8%). There was insufficient evidence that DTIC offered any advantage to event free survival, but there was evidence for better outcome for patients in Group III disease in comparison to patients with Group IV disease, and for patients with a Grade 1 and 2 histology in comparison to Grade 3 lesions. Conclusions Combination chemotherapy with VACA and VACAD were insufficient to prevent recurrent or progressive disease in children and adolescents with high stage NRSTS. The use of vincristine/ifosfamide/doxorubicin with cytokine support is under study. Med. Pediatr. Oncol. 30:201–209, 1998. © 1998 Wiley-Liss,Inc.

Granulocytic sarcoma in children with acute myeloblastic leukemia and t(8;21).

Abstract: Background Granulocytic sarcomas (GS) have been associated with t(8;21) The prognosis of patients with GS is generally regarded as being less favorable than of patients with acute myeloblastic leukemia (AML) GS occurs relatively commonly in Africa and has been reported to affect 10–25% of black children presenting with AML We sought to establish the incidence of GS in our pediatric population, to determine whether an association with t(8;21) existed, and to report on the outcome of these cases in a single series Procedure The records of consecutive pediatric patients treated for de novo AML in Johannesburg between January 1985–December 1995 were reviewed Fifteen cases of GS among a total of 88 cases of AML presented to the Paediatric Haematology/Oncology Clinics of the Johannesburg and Baragwanath Hospitals Fourteen (93%) of these patients were black male children Results All 9 cases of orbital GS (60%) and almost all cases with concurrent AML M2 had t(8;21) This translocation was present in only 4 (85%)of the remaining 47 AML cases without GS for which cytogenetic data were available One case presented with a complex chromosomal translocation not previously associated with GS The median disease-free survival of the GS patients, using conventional chemotherapy treatment protocols, was significantly better than for the patients with AML and no GS (P= 00004) Conclusions Our data support a strong association between orbital GS, t(8;21), and AML M2 in the pediatric population This entity occurred virtually exclusively in black male children at presentation One third of these children who presented with AML had a GS The favorable prognosis noted in our GS patients on standard induction and intensification therapy without local irradiation conflicts with some previous reports but is consistent with the favorable outcome documented in AML with t(8;21) Med Pediatr Oncol 31: 144–149, 1998 © 1998 Wiley-Liss, Inc

Growth and endocrinological disorders up to 21 years after treatment for acute lymphoblastic leukemia in childhood

Abstract: Background Our aim was to evaluate endocrinological status 10–21 years after treatment for childhood acute lymphoblastic leukemia (ALL) with chemotherapy (C) and cranial irradiation (C + I) or only C, and to correlate the endocrine data with growth parameters. Procedure. Of 30 patients (15 females and 15 males), 18 were treated with C + I and 12 were treated with C only. Height standard deviation score (HSDS) and body mass index standard deviation score (BMISDS) before treatment, at end of treatment, and at follow-up were calculated from height and weight registered from the charts. At follow-up examinations, provocative growth hormone (GH) tests (clonidine and insulin tolerance test) and an ACTH test were performed. Furthermore, blood samples for hormonal analysis, IGF-I, IGFBP-3, GHBP, and leptin were drawn. Results. Eleven patients (9 treated with C + I and 2 treated with C) showed insufficient response to GH tests. Two patients had hypogonadism. HSDS and IGF-I were significantly lower and GHBP significantly higher in GH-deficient patients compared to the group with normal GH secretion at follow-up. BMISDS steadily increased from start of treatment until follow-up, independent of GH status at follow-up. BMISDS at follow-up was positively correlated with serum leptin (P < 0.001), and serum leptin was significantly higher in the cranial irradiated group as compared to the nonirradiated group. Conclusions. GH deficiency is frequently found at long-term follow-up in patients treated for childhood ALL. Other hormonal deficiencies are rare. HSDS at long-term follow-up is dependent on GH secretory status. Long-term endocrinological follow-up examinations in patients treated for childhood ALL are recommended, as hormonal replacement therapy may be indicated. Med. Pediatr. Oncol. 30:351–356, 1998. © 1998 Wiley-Liss, Inc.

Electronic measurement of compliance with mercaptopurine in pediatric patients with acute lymphoblastic leukemia.

Abstract: Twenty-four pediatric patients with acute lymphoblastic leukemia (ALL) on maintenance therapy were evaluated for their compliance with taking their prescribed doses of oral mercaptopurine (6-MP). Procedure and Results. We utilized the Medication Event Monitoring System (MEMS; Aprex Corporation, Fremont, CA) for the study. Compliance was defined as the number of days doses were taken as a percentage of the total number of days doses were prescribed during the study period. The mean age of the patients was 7.3 years (range 2.6-17.2 (years). Patients were evaluated for a mean of 44 days (range 15-94 days). Thirty-three percent of patients (8) took less than 90% and 17% (4) took less than 80% of their prescribed pills. Eight patients were also evaluated for a difference in compliance between morning and evening administration. For the comparison of compliance between a morning vs. an evening schedule a trend toward improved compliance in the evening was found. Five patients had an increase and one patient a decrease in compliance with an evening schedule (differences ranged from 0.2% to 51.3%), with two patients having 100% compliance on both schedules. Conclusions. Our data raise concern that a significant proportion of pediatric patients are non-compliant with pill taking and demonstrate that the timing of administration of 6-MP in children with ALL may be crucial in some patients and supports the hypothesis that evening administration of 6-MP is associated with a lower risk of relapse.

Dental abnormalities in children treated for neuroblastoma.

Abstract: Purpose To determine the frequency and types of dental abnormalities among children treated at a young age for cancer, as represented by neuroblastoma. Patients and Methods We retrospectively reviewed the dental records and panoramic radiographs of 542 children who were treated for neuroblastoma at our institution over a 31-year period. Patients in our study had to meet the following criteria: they were treated on an institutional protocol, they had undergone panoramic radiography, and their dental follow-up continued for at least 2 years after diagnosis. We evaluated the frequency of clinically or radiographically apparent microdontia, excessive caries, root stunting, hypodontia, and enamel hypoplasia in our study population. Results Of the 52 patients who met the study criteria, 71% developed dental abnormalities, comprising microdontia in 38%, excessive caries in 29%, root stunting in 17%, hypodontia in 17%, and enamel hypoplasia in 17%. In nearly half (23) of our patients, neuroblastoma was diagnosed on or before their first birthday. Conclusion Children treated for neuroblastoma are at high risk for abnormal dental development. The abnormalities in these patients may require extensive dental care and can compromise their quality of life. Frequent dental examinations and an intense oral hygiene program before, during, and after treatment may improve overall dental health. Med. Pediatr. Oncol. 30:22–27, 1998. © 1998 Wiley-Liss, Inc.

Subsequent quality of life for children irradiated for a brain tumor before age four years.

Abstract: Background We wanted to evaluate survival and functional morbidity following radiation treatment of brain tumors in children less than 4 years old. Procedure Outcome was evaluated for 222 children who were less than 4years old when they were irradiated at University of Toronto Centres, 1958–1995. The status of the survivors with regard to focal neurological defects, vision, hearing, and education at last follow-up was recorded. In 23 adult survivors older than 21 years at last follow-up, information was obtained with regard to higher education, occupation, and living arrangements. Results The overall 10-year survival rate was 40%, not significantly different than the 45% for 776 4–16-year-olds with irradiated brain tumors treated at the same institutions. Forty-five percent of the survivors had no major focal neurological, visual, or hearing defects. There were no major differences in the frequencies of these criteria or of schooling between 0–2- and 2–4-year-olds. Among adult survivors, older than 21 at last follow-up, 26% successfully completed higher education, 31% were in full-time employment, and 37% had never been employed. For medulloblastoma, the 5-year survival rate was 61% for 30 children less than 3 years old and treated from 1975–1995. This compared favorably with recent reports of survival following primary chemotherapy with delayed or omitted radiation treatment. Summary Radiation treatment of a young child with a brain tumor was associated with cure in 1 of every 3 patients. Unfortunately, quality of life for many survivors was not good. Only one of every 3 adult survivors was able to have a normal life-style. This shortfall was the result of focal neurological defects which were present from the time of first treatment, and of the long-term effects of radiation treatment. Conclusions The search for less toxic treatment remains appropriate, but is experimental and researchers must recognize that there may be a trade-off between morbidity and mortality. Med. Pediatr. Oncol. 31:506–511, 1998. © 1998 Wiley-Liss, Inc.

Nasopharyngeal carcinoma in childhood and adolescence

Abstract: Background This study reviews the authors' experience from 1979 through 1996 in the management and outcome of 56 patients with nasopharyngeal carcinoma who were under 20 years of age. Procedure There were 33 males and 23 females, their ages ranging from 7 to 19 years (median: 16 years). Forty patients had World Health Organization type III carcinomas, 16 had T4 tumors, 41 had metastatic cervical lymph nodes, and 50 were at stage III or stage IV. Thirty-two patients were treated with radiation therapy alone and 24 with the addition of chemotherapy. Cumulative radiation dose to the primary tumor ranged from 18 to 70 Gy (median: 66 Gy) and radiation dose to metastatic cervical lymph nodes ranged from 18 to 70 Gy (median: 66 Gy). Results Follow-up ranged from 0.1 to 16.8 years (mean: 9 years). Locoregional tumoral complete response was achieved in 49 patients. Locoregional tumoral failure was observed in 12 patients and systemic failure in 11. Overall, locoregional failure-free, metastases-free, and disease-free survival rates at 5 years were 49%, 62%, 79%, and 47%, respectively, for the entire group of patients, 42%, 61%, 72%, and 42%, respectively, for patients treated with radiation therapy alone, and 58%, 63%, 87%, and 54%, respectively, for patients treated with the addition of chemotherapy. Advanced T-stage and lower radiation doses worsened locoregional failure-free survival, whereas advanced N-stage and exclusion of chemotherapy worsened metastases-free survival. Conclusions In children and adolescents with nasopharyngeal carcinoma, radiation therapy alone results in an improved locoregional tumoral response rate and a reduced locoregional tumoral failure rate at higher radiation doses, while the addition of chemotherapy results in a reduced systemic failure rate. Med. Pediatr. Oncol. 31:498–505, 1998. © 1998 Wiley-Liss, Inc.

Stratification of treatment of stage 4 neuroblastoma patients based on N-myc amplification status

Abstract: Background. It has been shown that children aged more than 12 months with stage 3 and 4 neuroblastoma with N-myc amplification do worse than those without amplification. Development of an innovative chemotherapeutic protocol for patients in such an extremely poor-risk group was the purpose of this study. Procedure. Since March 1991 a new protocol for the treatment of advanced neuroblastoma was started. When N-myc was amplified more than 10-fold, patients received regimen A 3 , in which cyclophosphamide 1,200 mg/m 2 was given on days 1 and 2; hence the dose of cytotoxic drugs was doubled. Patients with fewer than 10 copies of N-myc received regimen new A 1 , which is very similar to regimen A 1 that had been used until March 1991 for all patients with advanced neuroblastoma with/ without N-myc amplification. The efficacy of regimen A 3 was evaluated. Results. The relapse-free survival rate at 1 and 2 years for stage 4 patients older than 12 months of age with N-myc amplification of more than 10-fold was 43% and 29%, respectively, with regimen A, and that for the same subgroup of patients treated with regimen A 3 since March 1991 was 79% and 49%, respectively ; the difference is statistically significant. On the other hand, there were no differences in the relapse-free survival rate at 1 year and 2 years for stage 4 patients with fewer than 10 copies of N-myc between those treated with regimen A 1 and those treated with new A 1 since March 1991. Conclusions. Stratification based on N-myc amplification into new A, and A 3 treatment protocols is of significant clinical importance. Regimen A, was well tolerated and showed an improvement in clinical results in stage 4 patients with N-myc amplified more than 10-fold.

Matrix metalloproteinase-9 (MMP-9) expression in childhood osseous osteosarcoma.

Abstract: Background Over 80% of patients with osteosarcoma treated with excision alone develop pulmonary metastases, suggesting that the majority of patients with this disease harbor “micrometastases” at diagnosis. There are no histologic or molecular variables which can predict the presence or absence of micrometastasis. Matrix metalloproteinases (MMPs) are a class of matrix- and basement membrane-degrading enzymes whose expression is associated with tumor cell invasive and metastatic behavior. One of these enzymes, MMP-9 or gelatinase B, is expressed in developing and remodeling bone and in osteosarcoma cell lines. We speculated that MMP-9 expression might be associated with the micrometastatic behavior of osteosarcoma. Procedure We examined a series of pediatric primary osseous osteosarcomas and metastases for the expression of MMP-9, using a monoclonal antibody. Results We found intense MMP-9 immunostaining in most tumor cells in all samples of pretreatment osteosarcomas. In all postchemotherapy resection samples, tumor cells stained similarly, but there were fewer positively staining cells overall. In 4 of 5 metastastic lesions examined, intense immunostaining for MMP-9 was detected. Conclusions These results suggest that MMP-9 expression is common in osteosarcoma, and that further study of the role of MMP-9 in pediatric osteosarcoma behavior is warranted. Med. Pediatr. Oncol. 31:471–474, 1998. © 1998 Wiley-Liss, Inc.

Hepatoblastoma incidence in the United States from 1973 to 1992.

Abstract: Background There is recent evidence to suggest that extremely low birth weight is associated with the occurrence of hepatoblastoma. Procedure In light of this possibility, we evaluated trends in hepatoblastoma incidence in the United States among children age 4 years and younger. Results We found an increasing trend (5.2%) in hepatoblastoma incidence over the past two decades, a period that corresponds with improved survival of very low birth weight children. Conclusion Future studies of hepatoblastoma that incorporate birth weight are appropriate. Med. Pediatr. Oncol. 30:141–142, 1998. © 1998 Wiley-Liss,Inc.

Secondary thyroid carcinoma after treatment for childhood cancer.

Abstract: Background Second malignant neoplasms (SMNs) have become a primary concern in evaluating long-term effects of treatment in pediatric oncology. Thyroid carcinoma has proven to be a common SMN. Methods. In a multicenter study involving 58 hospitals in Germany, Austria and Switzerland, 18 of 239 (7.5%) SMNs documented following first malignant neoplasm (FMN) in childhood were thyroid carcinoma. Results. The age at diagnosis of FMN ranged from 1 to 15 years. Eleven patients were female. Six children had survived Hodgkin disease, seven acute leukemia, two Ewing sarcoma and three various other tumors. Fifteen of the 18 patients had been treated with radiotherapy to the head and neck region. The time interval between treatment and diagnosis of thyroid carcinoma ranged from 4 to 19 years (median 8 years). The carcinoma was papillary in 17 cases and follicular in one. Eleven patients had metastases in the regional lymph nodes at presentation. Discussion. Radiotherapy appears to be an important risk factor in secondary thyroid carcinoma, but it does not explain all cases. The current data are remarkable for the large proportion of patients who received only prophylactic cranial irradiation for ALL and for the three patients who received no irradiation to the head and neck region. Genetic determinants and chemotherapy must also be considered. Conclusions. Regular thyroid examination should be included in the long-term follow-up of survivors of childhood malignancy. Med. Pediatr. Oncol. 31:91–95, 1998. © 1998 Wiley-Liss, Inc.

UKCCSG's germ cell tumour (GCT) studies: improving outcome for children with malignant extracranial non-gonadal tumours—carboplatin, etoposide, and bleomycin are effective and less toxic than previous regimens

Abstract: Background We report the efficacy and late effects of carboplatin, etoposide, and bleomycin (JEB) for extracranial non-gonadal tumours (GCII, 1989-95) compared with the 5 previous regimens (GCI, 1979–1988) consisting of 3 vincristine, actinomycin, and cyclophosphamide (VAC) and 2 platinum-based protocols. Methods and Results Median follow-up for 52 patients in the GCI study and 46 in GCII was 105 and 48 months, respectively. For GCI, 5- and 10-year actuarial survival was 63% (95% Confidence Interval 50 to 75%) or 72% (57 to 83%) if 6 cases given low-dose VAC were excluded. For GCII, 5-year survival was significantly greater at 95% (83 to 99%), P = 0.01. Event-free survival was 46% at 5 years for GCI (33 to 59%) or 52% excluding the low-dose VAC cases (38 to 66%), while forGCII it was 87% (74 to 94%), P = 0.002. Five-year event-free survival of 21 children given cisplatin, etoposide, and bleomycin (BEP) in GCI was 57% (37 to 76%) compared with 87% (74 to 94%) for 46 given JEB in GCII, P = 0.02. Late effects in 30 evaluable survivors of GCI and 43 of GCII included renal impairment in 6 in GCI and 0 in GCII and deafness in 11 and 4, respectively. Among 17 survivors of sacrococcygeal tumours treated in GCI, 4 have neuropathic bladder/bowel and another shortening of a leg. In GCII, 4 of 26 have neuropathic bladder/bowel with lower limb weakness in one. Conclusions We found JEB to be more effective and less toxic than our previous regimens. Some survivors of sacrococcygeal tumours have neurological late effects. Med. Pediatr. Oncol. 30:217–227, 1998. © 1998 Wiley-Liss,Inc.

Outcome of patients with a history of bilateral retinoblastoma treated for a second malignancy: The Memorial Sloan‐Kettering Experience

Abstract: Background. Patients with bilateral retinoblastoma are well recognized to have high risk of developing a second malignancy, but there are little published data regarding the outcome of these patients following treatment. Patients and Methods. We identified 15 patients with a history of bilateral retinoblastoma who received treatment at Memorial Sloan-Kettering Cancer Center for a newly diagnosed second malignancy. The median age of second tumor occurrence was 18 years (range 10-32 years). Three patients later had a third tumor (18 tumors total). Tumor sites included facial structures in 14 cases and extremities in 4. Histologies included osteosarcoma (5), leiomyosarcoma (5), high-grade spindle cell sarcoma (3), malignant fibrous histiocytoma (3), malignant mesenchymoma (1), and angiosarcoma (1). Results. Nine patients are alive: 7 disease free at a median of 29 months (range 6-214 months) and 2 with residual disease 59 and 148 months post-diagnosis of the second malignancy. Six patients have died at a median of 31 months (range 16-98 months) after diagnosis of the second malignancy. Conclusions. Patients with a history of bilateral retinoblastoma who develop a second malignancy may enjoy extended periods of survival. Aggressive therapy appropriate to the tumor histology and site is indicated.

Guidelines for a therapeutic alliance between families and staff : A report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology

Abstract: This, the fifth official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, develops another important topic: the Therapeutic Alliance between families and staff. This is addressed to the Pediatric Oncology Community as Guidelines that could be followed. Every parent, medical staff member, and psychosocial professional involved in the care of the child should be responsible for cooperating in the child's best interest. Everyone must work together toward the common goal of curing the cancer and minimizing its medical and psychosocial side-effects.

Carboplatin and etoposide with hyperfractionated radiotherapy in children with newly diagnosed diffuse pontine gliomas: A phase I/II study

Abstract: Background Diffuse pontine gliomas remain one of the most lethal of pediatric malignancies despite the use of increasingly intensive therapies. We delivered intensive chemotherapy during and following 70.2 Gy of hyperfractionated radiation therapy in an attempt to improve survival. Procedure Nine consecutive children with diffuse pontine gliomas were treated on this single arm study. Carboplatin, given in combination with fixed dose etoposide, was escalated in successive cohorts to determine its maximum tolerated systemic exposure (AUC). Outcome was coded based on imaging characteristics and clinical status. Results Eight of the nine children on thisstudy died of their disease at a median of 44 weeks, essentially the same survival as those treated on a previous Pediatric Oncology Group study using hyperfractionated radiation therapy alone. Toxicity was almost exclusively hematologic and not associated with significant morbidity. Conclusions The use of concurrent carboplatin and etoposide with hyperfractionated radiation therapy did not appear to improve the survival in this group of children with diffuse pontine gliomas. The toxicity of this chemotherapy during radiation therapy was primarily hematologic and well tolerated. New approaches to the treatment of these tumors need to be investigated. Med. Pediatr. Oncol. 30:28–33, 1998. © 1998 Wiley-Liss, Inc.

Clinical and epidemiologic studies of familial hemophagocytic lymphohistiocytosis in Japan

Abstract: Background and Procedure The etiology of familial hemophagocytic lymphohistiocytosis (FHL), which is characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, remains unknown. We analyzed 43 FHL patients, all with affected siblings, in 18 families who were identified during the period 1986–1995 in Japan. Results The presence of consanguinity was evident in two families (11%). The majority of families lived in western Japan, where the frequency of consanguineous marriage is high. The incidence of FHL was significantly higher in the western island, Kyushu, than in other areas. The segregation ratio calculated for these families was 0.35 by the Weinberg proband method, showing the autosomal-recessive inheritance of the disease. Since the diagnosis of an FHL patient without affected siblings (sporadic case) is quite difficult, we calculated the possible number of sporadic cases; approximately 122 patients could be identified as spo-radic FHL cases during the same period in Japan. Most of the clinical and laboratory findings were not distinguishable from those of other types of lymphohistiocytosis. However, atypical lymphoid cells with azurophilic granules in peripheral blood were observed in half of the patients at diagnosis, suggesting the clinical importance of this parameter for early diagnosis. Despite intensive therapy, the prognosis of FHL was extremely poor; but 4 of the 8 patients who have survived had received bone marrow transplantation (BMT), indicating the effectiveness of BMT for this disorder. Conclusions The distribution of FHL in areas of highly frequent consanguineous marriage and the segregation analysis indicated a genetic factor in FHL. The identification of the genes for FHL is expected to contribute to a cure for this disorder, and might also enable FHL carrier detection and donor selection for BMT. Med. Pediatr. Oncol. 30:276–283, 1998. © 1998 Wiley-Liss, Inc.

Evaluation of quality of life of childhood cancer survivors: a methodological conundrum.

Abstract: QOL assessment in pediatric oncology is seriously understudied, especially compared with the adult population. The limited progress is due to the methodological complexity of the task, which should not be viewed as insurmountable. Given a precise study question, the methodological issues can be clarified simply, piece by piece. Researchers must consider very carefully the specific characteristics that define a study population in order to choose an instrument that is domain-appropriate and valid for the assessment paradigm. The first priority should be that a researcher must identify the means of accessing the information of interest. In the pediatric population, information about children's status may be elicited from parents, medical personnel, teachers, or the children themselves. Clearly, the type of instrument to be used for assessment is dependent on the choice of reporter. Researchers must also account for developmental age and disease; in assessing generic and disease-specific functioning, the "functional scale" against which an individual is compared must implicitly reflect the types of activities and/or levels of functioning that are realistic norms for the patient. Equally important is the analysis of independent domains in order to characterize the dynamics/divergence of clinical status and functional status. What are the merits of conducting QOL research for the pediatric cancer-survivor population? The policy implications are profound and pervasive both for the individual survivors (regarding treatment, care, and his/her ultimate ability to reintegrate into society) and for society (regarding resource allocation, cost planning, and productivity). Commensurate with the rapid advancement of oncologic therapy, there is now an expanding cohort of pediatric cancer survivors. Current estimates suggest that, by the turn of the century, 200,000 children will be in this category. The long-term survivorship of this cohort is still poorly defined. However, as the survivors mature, it is likely that their needs will evolve as well-whether for treatment of secondary malignancies, long-term morbidities, and fertility issues or for neuropsychological dysfunction, emotional counseling, or occupational issues. Children, as survivors, are unique, in that their future (the context within which long-term outcome is defined) spans decades. Based on a median age at diagnosis of 6 years, survivors can expect to live an additional 66 years. From a cost or policy perspective, children represent enormous future potential. The implications of children's long-term outcomes must be considered regarding the change in future potential secondary to survivorship. Pediatric QOL research plays a role both inside and outside the health care system. Clearly, in the provision of health care, QOL data may be used to improve or modify patient care by supplementing information about the clinical status of individual patients. Information about an individual's general functioning, particularly as it diverges from disease-specific functioning, complements clinical data to facilitate comprehensive care. Information about the long-term outcomes of pediatric cancer, as a whole, will influence the policies of health care institutions and the allocation of health care resources. By expanding the scope of survivorship (or cure) to include long-term clinical and general "costs" the "cost of cure" is shifted: this shift will ultimately impact estimations of cost effectiveness, with ramifications for the evaluation of hospital-wide protocols, utilization priorities, and cost policies. Outside of the hospital, the implications of QOL research are equally ubiquitous. Pediatric survivors will live an estimated 7 decades after "cure," during which time they will exist almost entirely outside the realm of health care; yet, their condition as a survivor, with or without the long-term clinical toxicities secondary to treatment, will continue to affect some or all of thei

Treatment of children with relapsed soft tissue sarcoma : Report of the German CESS/CWS REZ 91 trial

Abstract: Background The present study was performed to evaluate the possibilities of relapse treatment in patients heavily pretreated for a soft tissue sarcoma. Patients and Methods Prospective, multicenter study in 44 soft tissue sarcoma (STS) patients with first relapse. Primary diagnosis was embryonal rhabdomyosarcoma (RME) in 17 patients, alveolar rhabdomyosarcoma (RMA) in 13, primitive neuroectodermal tumor (PNET) in 6, and miscellaneous soft tissue sarcomas in 8 patients. Initial chemotherapy consisted of carboplatin/etoposide combination (150 mg/m2 each, days 1 to 4) followed by local therapy including surgical treatment and, whenever possible, radiotherapy. Results In 11/17 patients without primary tumor resection, CR or PR was achieved following the initial two cycles of chemotherapy (61%). The probability of event-free survival (pEFS) for RME patients was 0.41 ± 0.12 at 5 years, and 0.25 ± 0.12 for RMA patients. But, in contrast no PNET patient or patient with another soft-tissue sarcoma achieved long-term remission. Additional local radiotherapy significantly (P = 0.002) improved pEFS (3-year estimates of 0.23 ± 0.2 vs. 0.1 ± 0.1 in patients without radiotherapy). Conclusions In patients with RME, relapse treatment employing a carboplatin/etoposide combination may induce a second remission in approximately 40% of patients. Surgical excission and additional local radiotherapy seem to be essential to maintain a stable remission. In patients with RMA or PNET, however, this treatment strategy is of no long-term benefit. Med. Pediatr. Oncol. 30:269–275, 1998. © 1998 Wiley-Liss, Inc.

Effect of steroid and high-dose immunoglobulin therapy on opsoclonus-myoclonus syndrome occurring in neuroblastoma

Abstract: The authors describe a case of an 8-month-old boy with opsoclonus-myoclonus syndrome (OMS) and coincident unresectable neuroblastoma (NB). He achieved a complete remission for NB after 6 courses of standard-dose chemotherapy without significant neurological improvement despite the use of steroids and high-dose immunoglobulin (HIG), administered separately. Only the combined treatment withthese two drugs induced a complete disappearance of neurological symptoms. On the basis of this experience, the authors suggest the association of steroids plus HIG for the treatment of OMS in patients not responsive to conventional first line therapy with steroids.