Biomedical subjects

N K Cheung

Publications and source records attributed to N K Cheung.

At least 19 recordsLinked to original sources

PubMed2006

Primary trauma diversion: initial experience in Hong Kong.

BACKGROUND: Trauma is a leading cause of death and loss of workdays in Hong Kong. Reports have suggested that timely provision of care in dedicated trauma centers can improve outcomes. Until recently, ambulances were required to take trauma patients to the nearest hospital's emergency department. This paper reports on the initial experience of primary trauma diversion from scene to a dedicated trauma center in Hong Kong. METHODS: This prospective study involved the establishment of primary trauma diversion in the area served by Alice Ho Nethersole Hospital (AHNH), a general hospital in the New Territories. Trauma patients who fulfilled diversion criteria were taken directly to the Prince of Wales Hospital (PWH) in Shatin, a university teaching hospital and trauma center for the area. Data were collected to determine the change in time to definitive care for trauma patients and an impact analysis on PWH services was performed. RESULTS: There were 60 patients who underwent primary trauma diversion and 35 patients underwent secondary diversion after initial treatment at AHNH. This represented two extra trauma patients per week at PWH. Median Injury Severity Score (ISS) was 9 and 52% of patients had been involved in a traffic crash. Of eligible patients, 76% (69 out of 91) diverted correctly according to protocol. Primary trauma diversion patients reached definitive care 97 minutes faster than patients undergoing secondary diversion. CONCLUSION: Primary trauma diversion is feasible in Hong Kong and means that patients reach definitive care 97 minutes faster than going to the nearest hospital. Primary trauma diversion protocols should be extended throughout Hong Kong.

Adult↗

PubMed2005

Reduced time on the spinal board-effects of guidelines and education for emergency department staff.

AIM: Prehospital spinal immobilisation is usually accomplished with a spinal board. Prolonged immobilisation on spinal boards in the emergency department (ED) can be detrimental. This study aimed to reduce the time spent by patients on spinal boards using a staff education program. METHODS: Observational study in a trauma centre ED seeing 180,000ED attendances per year. The length of time immobilised on spinal board was recorded by the trauma nurse coordinator. Guidelines on removal of spinal boards were issued after recording period 1 (January-June 2001) and reinforced several times. The post-training period (period 2) extended from May to October 2003. Medians were compared using Mann-Whitney U-test (non-parametric data); chi-square test was used for categorical data. RESULTS: There were 122 eligible patients in period 1 and 104 eligible patients in period 2. Median time to removal from the spinal board was reduced by 18.5 min from 50 to 31.5 min (Mann-Whitney U-test, p<0.0001, 95% CI for difference in medians 13-29 min). In period 1, 44 of 122 patients (36%) were removed from the spinal board before leaving the ED, compared to 78 of 104 patients (75%) in period 2 (p<0.0001, chi-square test). CONCLUSION: The introduction of guidelines, reinforced by ED staff education, can significantly reduce the time patients spend on spinal boards after trauma and can increase the proportion of patients who can be removed from the board before leaving the ED.

Education, Continuing↗

PubMed2001

Phase II trial of the anti-G(D2) monoclonal antibody 3F8 and granulocyte-macrophage colony-stimulating factor for neuroblastoma.

PURPOSE: To describe oncolytic effects of treatment with anti-G(D2) monoclonal antibody 3F8 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with neuroblastoma (NB). PATIENTS AND METHODS: Patients were eligible for 3F8/GM-CSF if intensive therapy had not eradicated potentially lethal NB. One cycle consisted of GM-CSF (subcutaneous bolus) on days 1 through 5, 11, and 12, and GM-CSF (2-hour intravenous [IV] infusion) followed after a 1-hour interval by 3F8 (1.5-hour IV infusion) on days 6 through 10 and 13 through 17. GM-CSF was dosed at 250 microg/m(2)/d on days 1 through 7 and at 500 microg/m(2)/d on days 8 through 17. 3F8 was dosed at 10 mg/m(2)/d (100 mg/m(2)/cycle). 3F8 was given with an opiate and an antihistamine. Patients without progressive disease (PD) or elevated human antimouse antibody titers could be treated again beginning 3 weeks after completion of a cycle. RESULTS: Among 19 patients treated for NB resistant to induction therapy, 12 of 15 had complete remission (CR) of bone marrow (BM) disease, and three others who had less than partial responses achieved prolonged progression-free survival (one remains on study at 21+ months, two had PD at 12 and 17 months). Among patients treated for recurrent NB resistant to retrieval therapy, five of 10 had CR in BM. The 15 patients treated for PD fared poorly, although two had scintigraphic findings suggestive of a short-term response. Side effects were limited to readily manageable pain and, less commonly, rash of short duration; hence, patients were treated as outpatients. CONCLUSION: 3F8/GM-CSF is well tolerated and shows promise for treatment of minimal residual NB in BM.

Adolescent↗

PubMed2001

Neuroblastic and Schwannian stromal cells of neuroblastoma are derived from a tumoral progenitor cell.

The coexistence of neuroblastic and Schwannian stromal (SS) cells in differentiating neuroblastoma (NB), and derivation of Schwannian-like cells from neuroblastic clones in vitro, were accepted previously as evidence of a common pluripotent tumor stem line. This paradigm was challenged when SS cells were suggested to be reactive in nature. The advent of microdissection techniques, PCR-based allelic analysis, and in situ fluorescent cytometry made possible the analysis of pure cell populations in fresh surgical specimens, allowing unequivocal determination of clonal origins of various cell subtypes. To overcome the complexity and heterogeneity of three-dimensional tissue structure, we used: (a) Laser-Capture Microdissection to obtain histologically homogeneous cell subtype populations for allelotype analysis at chromosomes 1p36, 11q23, 14q32, and 17q and study of MYCN copy number; (b) multiparametric analysis by Laser-Scanning Cytometry of morphology, DNA content, and immunophenotype of intact cells from touch imprints; and (c) bicolor fluorescence in situ hybridization on touch imprints from manually microdissected neuroblast and stroma-rich areas. Histologically distinct SS and neuroblastic cells isolated by Laser-Capture Microdissection had the same genetic composition in 27 of 28 NB analyzed by allelic imbalance and gene copy number. In all 20 cases studied by Laser-Scanning Cytometry, SS cells identified by morphology and S-100 immunostaining had identical DNA content and GD2-staining pattern as their neuroblastic counterparts. In 7 cases, fluorescence in situ hybridization demonstrated the same chromosomal makeup for SS and neuroblastic cells. These results provide unequivocal evidence that neuroblastic and SS cells in NB are derived from genetically identical neoplastic cells and support the classical paradigm that NB arises from tumoral cells capable of development along multiple lineages.

Adolescent↗

PubMed2001

GD2 synthase: a new molecular marker for detecting neuroblastoma.

BACKGROUND: Neuroblastomas (NBs) almost ubiquitously express the ganglioside GD2. GD2 synthesis is dependent on the key enzyme GD2 synthase. Thus, GD2 synthase transcript may prove to be a potential molecular marker of NB. METHODS: Seventy-seven NB tumor tissues of all stages, 5 NB cell lines, and 26 normal bone marrows (BMs) and peripheral blood (PBL) samples, as well as 26 non-NB remission-BMs were analyzed for the expression of GD2 synthase by a highly sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) and chemiluminescence detection. One hundred fifty-two NB BMs were tested and comparisons were made among three independent detection techniques, namely GD2 synthase RT-PCR, immunofluorescence (IF), and histology (HIST). RESULTS: GD2 synthase transcript was present in 5 of 5 cell lines and in 77 of 77 tumors tested. Among 116 marrows that were positive by at least 1 of the 3 methods, 78% were detectable by GD2 synthase, 68% by IF, and 46% by HIST. Seventy-six percent of positive BMs that were obtained during treatment and follow-up had GD2 synthase expression, whereas only 29% were HIST positive. Correlation between RT-PCR and IF was high (P = 0.001), and positivity by 3 out of 3 methods was strongly correlated with poor survival (P < 0.01). Of note, marrows tested at the time of chemotherapy were positive by at least 2 out of 3 methods and were associated with adverse outcome (P = 0.01). Serial samples (n = 28) in 5 patients demonstrated close agreement between RT-PCR and patient disease status. CONCLUSIONS: The current study found that molecular detection of GD2 synthase transcript in NB BMs may have potential value in detecting rare tumor cells.

Biomarkers, Tumor↗

PubMed2001

Immunomagnetic purging of Ewing's sarcoma from blood and bone marrow: quantitation by real-time polymerase chain reaction.

PURPOSE: A propensity for hematogenous spread with resulting contamination of autologous cell products complicates cellular therapies for Ewing's sarcoma. We used a new approach to purge artificially contaminated cellular specimens of Ewing's sarcoma and show the capacity for real-time polymerase chain reaction (PCR) to quantify the contamination level of Ewing's sarcoma in such specimens. PATIENTS AND METHODS: Binding of monoclonal antibody (MoAb) 8H9 to Ewing's sarcoma cell lines and normal hematopoietic cells was studied using flow cytometry. Using real-time PCR--based amplification of t(11;22), levels of Ewing's contamination of experimental and clinical cellular products were monitored. Purging was accomplished using immunomagnetic-based depletion. Monitoring of the function of residual hematopoietic progenitors and T cells was performed using functional assays. RESULTS: MoAb 8H9 shows binding to Ewing's sarcoma but spares normal hematopoietic tissues. Nested real-time PCR is capable of detecting contaminating Ewing's sarcoma cells with a sensitivity of one cell in 10(6) normal cells. After 8H9-based purging, a 2- to 3-log reduction in contaminating Ewing's sarcoma was shown by real-time PCR, with purging to PCR negativity at levels of contamination of 1:10(6). Levels of contamination in clinical samples ranged from 1:10(5) to 10(6). Therefore, 8H9-based purging of clinical samples is predicted to reduce tumor cell contamination to a level below the limit of detection of PCR. CONCLUSION: These results demonstrate a new approach for purging contaminated cellular products of Ewing's sarcoma and demonstrate the capacity of real-time PCR to provide accurate quantitative estimates of circulating tumor burden in this disease.

Animals↗

PubMed2001

Genetic heterogeneity and clonal evolution in neuroblastoma.

Tumour heterogeneity and clonal evolution at the genetic level may explain the development of malignant or resistant disease during clinical progression of neuroblastoma (NB). In this report we use 1p allelic analysis and DNA ploidy to evaluate clonal heterogeneity and clonal selection in vivo. We studied a total of 69 tumours from 29 patients with NB. To evaluate tumour heterogeneity and clonal evolution in vivo we used a panel of polymorphic allelic markers mapping to chromosome 1. 33 tumours from 12 patients (group 1) were obtained from different sites during the same surgery or at sequential surgeries without intervening chemotherapy to evaluate genetic heterogeneity. Paired samples from 10 patients (group 2) were used to evaluate clonal selection before and after chemotherapy. In 6 cases paired tumours and derived cell lines were studied. Analysis of DNA ploidy changes by karyotype, FISH and flow cytometry was performed in 15 tumours from 6 multiply recurred local-regional (LR) NB patients. Allelotype study revealed that 66% (8/12) of group 1 samples were heterogeneous, with distinct allelic patterns in tumour samples separated by time or location. In group 2 allelic patterns were different in post-chemotherapy specimens in 60% (6/10). DNA ploidy analysis showed that pre-chemotherapy samples contained 2 distinct ploidy clones, one diploid and one triploid, whereas all post-chemotherapy tumor samples were 100% diploid. These findings suggest that NB exhibits a high degree of clonal heterogeneity and clonal evolution occurs during the course of therapy and clinical progression.

Chromosomes, Human, Pair 1↗

PubMed2001

Extending positron emission tomography scan utility to high-risk neuroblastoma: fluorine-18 fluorodeoxyglucose positron emission tomography as sole imaging modality in follow-up of patients.

PURPOSE: Although positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ((18)F-FDG) has a major impact on the treatment of adult cancer, the reported experience with extracranial tumors of childhood is limited. We describe a role for PET in patients with neuroblastoma (NB). PATIENTS AND METHODS: In 51 patients with high-risk NB, 92 PET scans were part of a staging evaluation that included iodine-123 or iodine-131 metaiodobenzylguanidine (MIBG) scan, bone scan, computed tomography (and/or magnetic resonance imaging), urine catecholamine measurements, and bone marrow (BM) examinations. The minimum number of tests sufficient to detect NB was determined. RESULTS: Of 40 patients who were not in complete remission, only 1 (2.5%) had NB that would have been missed had a staging evaluation been limited to PET and BM studies, and 13 (32.5%) had NB detected by PET but not by BM and urine tests. PET was equal or superior to MIBG scans for identifying NB in soft tissue and extracranial skeletal structures, for revealing small lesions, and for delineating the extent and localizing sites of disease. In 36 evaluations of 22 patients with NB in soft tissue, PET failed to identify only two long-standing MIBG-negative abdominal masses. PET and MIBG scans showed more skeletal lesions than bone scans, but the normally high physiologic brain uptake of FDG blocked PET visualization of cranial vault lesions. Similar to MIBG, FDG skeletal uptake was diffusely increased with extensive or progressing BM disease but faint or absent with minimal or nonprogressing BM disease. CONCLUSION: In the absence or after resolution of cranial vault lesions, and once the primary tumor is resected, PET and BM tests suffice for monitoring NB patients at high risk for progressive disease in soft tissue and bone/BM.

3-Iodobenzylguanidine↗

PubMed2001

Hyperfractionated low-dose radiotherapy for high-risk neuroblastoma after intensive chemotherapy and surgery.

PURPOSE: To assess prognostic factors for local control in high-risk neuroblastoma patients treated with hyperfractionated 21-Gy total dose to consolidate remission achieved by dose-intensive chemotherapy and surgery. PATIENTS AND METHODS: Patients with high-risk neuroblastoma in first remission received local radiotherapy (RT) totaling 21 Gy in twice-daily 1.5-Gy fractions. RT to the primary site followed dose-intensive chemotherapy and tumor resection; the target field encompassed the extent of tumor at diagnosis, plus 3-cm margins and regional lymph nodes. RT to distant sites followed radiologic evidence of response. Local failure was correlated with clinical factors (including other consolidative treatments) and biologic findings. RESULTS: Of 99 consecutively irradiated patients followed for a median of 21.1 months from RT, 10 relapsed in or at margins of RT fields at 1 to 27 months (median, 14 months). At 36 months after RT, the probability of primary-site failure was 10.1% +/- 5.3%. No primary-site relapses occurred among the 23 patients whose tumors were excised at diagnosis, but there were three such relapses among the seven patients who were irradiated with evidence of residual disease in the primary site. Four of 18 patients with MYCN-amplified disease and serum lactate dehydrogenase greater than 1,500 U/L had local failures (23.4% +/- 10.7% risk at 18 months). Acute radiotoxicities were insignificant, but three of 35 patients followed for > or = 36 months had short stature from decreased growth of irradiated vertebra. CONCLUSION: Hyperfractionated 21-Gy RT is well tolerated and, together with dose-intensive chemotherapy and surgery, may help in local control of high-risk neuroblastoma. Extending the RT field to definitively encompass regional nodal groups may improve results. Visible residual disease may warrant higher RT dosing. Patients with biologically unfavorable disease may be at increased risk for local failure. RT to the primary site may not be necessary when tumors are excised at diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors.

Tumor-restricted surface antigens may be targets for diagnosis and immune-based therapies. Monoclonal antibody 8H9 is a murine IgG1 hybridoma derived from the fusion of mouse myeloma SP2/0 cells and splenic lymphocytes from BALB/c mice immunized with human neuroblastoma. By immunohistochemistry, 8H9 was highly reactive with human brain tumors, childhood sarcomas, and neuroblastomas, and less so with adenocarcinomas. Among primary brain tumors, 15 of 17 glioblastomas, 3 of 4 mixed gliomas, 4 of 11 oligodendrogliomas, 6 of 8 astrocytomas, 2 of 2 meningiomas, 3 of 3 schwannomas, 2 of 2 medulloblastomas, 1 of 1 neurofibroma, 1 of 2 neuronoglial tumors, 2 of 3 ependymomas, and 1 of 1 pineoblastoma tested positive. Among sarcomas, 21 of 21 Ewing's/primitive neuroectodermal tumor, 28 of 29 rhabdomyosarcomas, 28 of 29 osteosarcomas, 35 of 37 desmoplastic small round cell tumors, 2 of 3 synovial sarcomas, 4 of 4 leiomyosarcomas, 1 of 1 malignant fibrous histiocytoma, and 2 of 2 undifferentiated sarcomas tested positive with 8H9. Eighty-seven of 90 neuroblastomas, 12 of 16 melanomas, 3 of 4 hepatoblastomas, 7 of 8 Wilms' tumors, 3 of 3 rhabdoid tumors, and 12 of 27 adenocarcinomas also tested positive. In contrast, 8H9 was nonreactive with normal human tissues including bone marrow, colon, stomach, heart, lung, muscle, thyroid, testes, pancreas, and human brain (frontal lobe, cerebellum, pons, and spinal cord). Reactivity with normal cynomolgus monkey tissue was restricted similarly. Indirect immunofluorescence localized the antigen recognized by 8H9 to the cell membrane. The antigen is proteinase sensitive and is not easily modulated off the cell surface. 8H9 immunoprecipitated a M(r) 58,000 band after N-glycanase treatment, most likely a protein with a heterogeneous degree of glycosylation. This novel antibody-antigen system may have potential for tumor targeting.

Animals↗

PubMed2001

Neuroblastoma metastatic to the central nervous system. The Memorial Sloan-kettering Cancer Center Experience and A Literature Review.

BACKGROUND: The central nervous system (CNS) can be a sanctuary site for cancer cells, because the blood-brain barrier impedes penetration of most chemotherapeutic agents. The authors hypothesized that, with improved survival from childhood metastatic neuroblastoma (NB), the incidence of CNS (intraparenchymal and leptomeningeal) spread may increase. They undertook this study to assess the frequency of CNS NB, to analyze risk factors and treatment options, and to review the literature. METHODS: The authors retrospectively analyzed all patients with metastatic NB who were treated on protocols N4, N5, N6, and N7 from 1980 to 1999 at Memorial Sloan-Kettering Cancer Center (MSKCC), during which time there was an increase in the overall survival rate. RESULTS: Two hundred fifty-one patients with Stage 4 NB (Group 251) were studied, of which 127 (Group 127) were newly diagnosed patients who were treated initially at MSKCC. None had CNS NB at the time of diagnosis. Eleven patients developed documented CNS disease; 8 of these 11 recurrences were isolated in the CNS. For Group 127, the overall incidence rate of CNS NB was 6.3%, with an increase in incidence from N4-N5 to N6-N7 of from 1.7% to 11.7%. Seven patients had isolated CNS disease recurrences. Only lumbar punctures (LP) performed near the time of diagnosis in patients with known bone marrow involvement were associated with subsequent development of CNS disease. For the entire group of 251 patients, lumbar puncture at the time of diagnosis and elevated serum lactic dehydrogenase levels were prognostic. Among the larger series reported in the literature, CNS involvement from metastatic lesions was rare at the time of diagnosis and remained an uncommon complication. CONCLUSIONS: The incidence of CNS NB may be increasing. Because it is the sole site of disease recurrence in 64% of patients, the CNS may represent a sanctuary site for NB. CNS NB is associated with diagnostic lumbar punctures in patients with known bone marrow disease, raising the possibility that circulating or epidural microscopic tumor cells may seed the craniospinal axis.

Adrenal Gland Neoplasms↗

PubMed2001

Survival analysis of clinical, pathologic, and genetic features in neuroblastoma presenting as locoregional disease.

BACKGROUND: Locoregional neuroblastoma is a clinical subgroup characterized by the absence of distant metastasis (International Neuroblastoma Staging System Stages 1, 2, and 3). Although these patients generally have an excellent survival with minimal therapy, some do experience recurrence with lethal consequences. METHODS: To identify risk factors for disease progression, the authors performed a retrospective analysis of clinical (age and stage) and tumor biologic markers (histology, MYCN, DNA index, and allelic analysis of chromosomes 1p, 11q12-qter, and 14q12-q32) in 44 patients (10 Stage 1, 18 Stage 2, and 16 Stage 3). Allelic analysis was performed using polymorphic polymerase chain reaction markers in a semiautomated, fluorescent detection system. RESULTS: Sixteen patients (38%) were younger than 365 days at diagnosis. Seventeen of 39 tumors (43%) had unfavorable histology, 6 (13%) were MYCN amplified, 14 (31%) were diploid, 17 (38%) had 1p36 loss of heterozygosity (LOH), 11 (25%) had 1p22 LOH, 10 (22%) had 11q LOH, and 13 (29%) had 14q LOH. Seventeen patients (38%) progressed, including 6 who progressed to Stage 4 disease (13%). Sixteen patients with progressive disease received cytotoxic therapy. Thirty-seven patients are alive (84%) with a median follow-up of 51 months. By permutation log rank test, both MYCN amplification and diploidy were associated with overall survival (OS), but only diploidy was associated with progression free survival (PFS) and progression to Stage 4 disease. LOH of 1p36, 1p22, 11q, or 14q did not show correlation with either OS or PFS. CONCLUSIONS: Locoregional neuroblastoma tumors with diploid DNA index, regardless of other biologic features, have increased risk of local recurrence and Stage 4 progression.

Child↗

PubMed2001

Disaloganglioside GD2 loss following monoclonal antibody therapy is rare in neuroblastoma.

BACKGROUND: Gangliosicle GD2 is abundant on human neuroblastoma (NB). Monoclonal antibody 3F8 targeted to GD2 may have imaging and therapeutic potential. Antigen-negative clones can escape immune-mediated attack leading to clinical resistance or recurrence. PROCEDURE: Among 95 evaluable patients treated intravenously with 3F8 (94 Stage 4, 1 Stage 3), 66 received nonradiolabeled 3F8, 11 received 131-iodine-labeled-3F8 (8-28 mCi/kg) with autologous bone marrow rescue, and 18 received both forms of treatment. Prior to treatment, 90 patients tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 68), tumor immunohistochemistry (n = 20), or diagnostic radioimmunoscintigraphy (n = 2). RESULTS: Of 62 patients who had refractory or recurrent neuroblastoma following 3F8 treatment, 61 (98%) tested positive for GD2 reactivity by bone marrow immunofluorescence (n = 51) or tumor immunohistochemistry (n = 10). The sole tumor that lost GD2 expression underwent phenotypic transformation into a pheochromocytoma-like tumor. CONCLUSIONS: The persistence of GD2 expression in refractory or recurrent NB suggests that complete antigen loss is an uncommon event and cannot account for treatment failure.

Antibodies, Monoclonal↗

PubMed2001

Detection of microscopic disease: comparing histology, immunocytology, and RT-PCR of tyrosine hydroxylase, GAGE, and MAGE.

BACKGROUND: We first explored the use of multiple molecular markers to overcome tumor heterogeneity. Sixty-seven neuroblastoma (NB) tumors were tested for the expression of GAGE, MAGE-2, MAGE-2, MAGE-3, and MAGE-4 by RT-PCR and then chemiluminescence; 82% of tumors had detectable GAGE, and 88% expressed at least one of the four MAGE genes. PROCEDURE AND RESULTS: By combining GAGE and MAGE, 64 of 67 (95%) of tumors became detectable; 17 of 67 coexpressed all five molecular markers. Neither GAGE nor MAGE expression correlated with stage. GAGE was found to have the broadest (18 of 18) expression among stage 4 tumors. Two hundred fifty-nine bone marrows from 99 patients were then studied for NB positivity by four detection methods: histology, immunocytology, and molecular detection by GAGE and tyrosine hydroxylase (TH) mRNA. Two hundred seven samples were NB-positive by one detection method. All four techniques were comparable in detecting tumor cells at diagnosis and at relapse. GAGE and immunocytology were far more sensitive than histology and TH mRNA when marrows were sampled during chemotherapy and at the time of clinical remission. CONCLUSIONS: By combining multiple molecular markers and independent screening techniques, we may be able to overcome tumor heterogeneity and expedite the detection of microscopic disease in the clinical management of neuroblastoma.

Algorithms↗

PubMed2001

N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age.

BACKGROUND: The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2). PROCEDURE: The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7. 131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates stem-cell support. RESULTS: Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21 of 24 patients. Twenty patients to date have completed treatment with 131I-3F8, and 15 patients have completed all treatment. With a median follow-up of 19 months, 18 of 24 patients remain progression-free. CONCLUSIONS: Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism.

Antibodies, Monoclonal↗

PubMed2001

Antibody-based diagnostic and therapeutic innovations for human cancer.

As adjuvants, antibody-based diagnostic and therapeutic innovations can potentially decrease morbidity and mortality associated with many human malignancies. Current strategies employing genetically modified constructs may improve tumor penetration and increase versatility.

Antibodies, Monoclonal↗

PubMed2001

Monoclonal antibody-based therapy of neuroblastoma.

The curative potential of mAbs in the treatment of patients with metastatic neuroblastoma is increasingly evident. The idiotype network appears to represent one component of a complex mechanism for success with mAb-based immunotherapy. Ongoing strategies to modify or reconstruct mAbs, to engage them with cytokines, or to unite them with T cells open new avenues for harnessing the unique forces of the immune system against some of the most deadly pediatric cancers.

Antibodies, Anti-Idiotypic↗

PubMed2001

Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults.

Topotecan appears to be relatively unaffected by the most common multidrug resistance mechanisms, may potentiate cytotoxicity of alkylators, has good penetration into the central nervous system, is active against a variety of neoplasms, and has myelosuppression as its paramount toxicity. We present our experience with a myeloablative regimen that includes topotecan. Twenty-one patients with poor-prognosis tumors and intact function of key organs received topotecan 2 mg/m2 by 30-min intravenous (i.v.) infusion on days -8, -7, -6, -5, -4; thiotepa 300 mg/m2 by 3 h i.v. infusion on days -8, -7, -6; and carboplatin by 4 h i.v. infusion on days -5, -4, -3 with a daily dose derived from the pediatric Calvert formula, using a targeted area under the curve of seven mg/ml* min ( approximately 500 mg/m2/day). Stem cell rescue was on day 0. The patients were 1 to 29 (median 4) years old; 18 were in complete remission (CR) and three in partial remission (PR). Early toxicities were severe mucositis and erythema with superficial peeling in all patients and a seizure, hypertension, and renal insufficiency followed by veno-occlusive disease in one patient each. Post-transplant treatment included radiotherapy alone (four patients) or plus biological agents (11 patients with neuroblastoma). With a follow-up of 6+ to 32+ (median 11+) months, event-free survivors include 10/11 neuroblastoma patients (first CR), 4/5 brain tumor patients (second PR or CR), 1/3 patients with metastatic Ewing's sarcoma (first or second CR), and a patient transplanted for multiply recurrent immature ovarian teratoma; a patient with desmoplastic small round-cell tumor (second PR) had progressive disease at 8 months. Favorable results for disease control, manageable toxicity, and the antitumor profiles of topotecan, thiotepa, and carboplatin, support use of this three-drug regimen in the treatment of neuroblastoma and brain tumors; applicability to other tumors is still uncertain.

Adolescent↗