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N K Cheung

Publications and source records attributed to N K Cheung.

At least 73 records · Page 4Linked to original sources
PubMed1998

Detection of microscopic neuroblastoma in marrow by histology, immunocytology, and reverse transcription-PCR of multiple molecular markers.

We explored the use of multiple molecular markers to overcome tumor heterogeneity. Sixty-seven neuroblastoma (NB) tumors were tested for the expression of GAGE, MAGE-1, MAGE-2, MAGE-3, and MAGE-4 by reverse transcription-PCR. Eighty-two percent of 67 NB tumors had detectable GAGE, and 88% expressed at least one of the four MAGE genes. By combining GAGE and MAGE, we found that 64 of 67 (95%) of tumors became detectable and 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. A total of 259 bone marrows from 99 patients were then studied for NB positivity by four detection methods: histology (aspirate by Wright-Giemsa and biopsy by H&E staining), immunocytology (by a panel of anti-GD2 monoclonal antibodies), and molecular detection by GAGE and tyrosine hydroxylase mRNA. Two hundred seven samples were NB positive by one or more detection methods. All four techniques were comparable in detecting tumor cells at diagnosis. GAGE and immunocytology were more sensitive than histology or tyrosine hydroxylase reverse transcription-PCR when marrows were obtained from patients on therapy or off therapy during clinical remission. Agreement among tests was highest at the time of gross disease. We conclude that, 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 NB.

Antigens, Neoplasm↗
PubMed1997

Additive cytotoxicity of different monoclonal antibody-cobra venom factor conjugates for human neuroblastoma cells.

Insufficient numbers of antigen molecules and heterogeneity of antigen expression on tumor cells are major factors limiting the immunotherapeutic potential of the few clinically useful monoclonal antibodies capable of mediating complement cytotoxicity and antibody-dependent cellular cytotoxicity. To overcome this limitation, we converted two non-cytotoxic monoclonal anti-neuroblastoma antibodies, designated 3E7 (IgG2b) and 8H9 (IgG1), and the non-cytotoxic F(ab')2 fragment of the cytotoxic monoclonal anti-GD2 antibody 3F8 (IgG3) into cytotoxic antibody conjugates by covalent attachment of cobra venom factor (CVF), a structural and functional homologue of the activated third component of complement. Competitive binding experiments confirmed the different specificities of the three antibodies. In the presence of human complement, all three antibody-CVF conjugates mediated selective complement-dependent lysis of human neuroblastoma cells. Consistent with the kinetics of the alternative pathway of complement, approximately seven hours incubation were required to reach maximum cytotoxicity of up to 25% for the 3E7-CVF conjugate, up to 60% for the 8H9-CVF conjugate, and up to 95% for the 3F8 F(ab')2-CVF conjugate. The different extent of maximal cytotoxic activity of the three conjugates was reflected by corresponding differences in the extent of binding of both unconjugated antibodies and the respective conjugates. Any combination of the three antibody-CVF conjugates caused an additive effect in complement-mediated lysis. Using a cocktail of all three conjugates, the extent of complement-mediated killing could be increased up to 100%. These data demonstrate that by coupling of CVF the relative large number of non-cytotoxic monoclonal anti-tumor antibodies of interesting specificity can be used to design cocktails of cytotoxic conjugates and, thereby, to overcome the problem of insufficient and heterogeneous antigen expression on tumor cells for immunotherapy.

Antibodies, Monoclonal↗
PubMed1997

Monoclonal antibody to human Trk-A: diagnostic and therapeutic potential in neuroblastoma.

5C3 is a murine IgG1 antibody specific for the nerve growth factor (NGF) docking site of the human p140 trk-A receptor, with no cross-reactivity with human trk-B. In vitro, 5C3 and its Fab mimic the effects of NGF, a neurotrophin mediating growth and differentiation of neural crest-derived cells. When labelled with radioisotope, 5C3 images human trk-A positive tumours in vivo. More importantly, 5C3 induces regression of human trk-A positive tumours in rodents. We therefore investigated the value of 5C3 in detecting trk-A expression in human neuroblastoma by immunohistochemistry. 5C3 reactivity was detected in 73 of 113 neuroblastoma specimens and correlated strongly with localised/4s disease (55/60) with either a homogeneous or mixed pattern. Among stage 4 neuroblastoma, only 18/53 had homogeneous or mixed trk-A expression. 5C3 did not react with 46/48 other human malignancies, but was positive in 1 melanoma and 1 Wilms' tumour specimen. The prognostic, imaging and NGF-mimetic properties of antibody 5C3 and its derivatives may offer alternatives for the diagnosis and treatment of neuroblastoma.

Antibodies, Monoclonal↗
PubMed1997

Correlation of MYCN amplification, Trk-A and CD44 expression with clinical stage in 250 patients with neuroblastoma.

In contrast to MYCN amplification, expression of either trk-A or CD44 in neuroblastoma is a favourable prognostic factor and were therefore investigated in tumours from 250 patients. One hundred and eleven localised/4s (Group 1) and 139 stage 4 (Group 2) tumours were analysed. MYCN copy number was obtained by Southern blotting or PCR amplification and was detected in 28 stage 4 tumours. Trk-A and CD44 expression was detected by immunoperoxidase staining using murine monoclonal antibodies 5C3 and L178, respectively. Expression was scored as positive (homogeneous), mixed (heterogeneous) or non-reactive (negative). Trk-A expression was found in 95% of Group 1 tumours and 49% of Group 2 tumours. CD44 expression was found in 100% of Group 1 tumours, the majority of which had a strong homogeneous expression. Lack of CD44 expression occurred in 25% of tumours, all stage 4 neuroblastoma. Of the 28 MYCN amplified tumours, 27/28 (96%) were trk-A negative, and 13/28 (46%) CD44 negative. We conclude that (1) a significant percentage of stage 4 neuroblastoma express either or both trk-A and CD44, (2) the absence of CD44 expression is highly restricted to stage 4 neuroblastoma and is associated with the lack of trk-A expression, (3) trk-A negativity among CD44-positive tumours is associated with stage 4 neuroblastoma and (4) the absence of trk-A expression is highly correlated with MYCN amplification.

Carrier Proteins↗
PubMed1997

Survival from non-stage 4 neuroblastoma without cytotoxic therapy: an analysis of clinical and biological markers.

The clinical characteristics of 43 patients (pts) and the biological features of their non-stage 4 neuroblastoma (11, 3, 15, 7 and 7 with stages 1, 2A, 2B, 3 and 4S, respectively) all managed initially without cytotoxic therapy at Memorial Sloan-Kettering Cancer Center are summarised. We staged patients by the International Neuroblastoma Staging System and measured their urine and serum tumour markers. Tumour MYCN copy number, chromosomal ploidy, chromosome 1p deletion, Shimada histopathology, trk-A and CD44 expression were analysed. Among patients with localised tumour (n = 36), 13 had residual disease after initial surgery, 19 had regional lymph node invasion and 6 had epidural involvement (2 of 6 being paraplegic). All 7 stage 4S patients had liver tumours, 3 had bone marrow involvement and 3 had lymph node involvement. The most common adverse biological markers were unfavourable histopathology (9/40 evaluable tumours) and diploidy (7/39 tumours tested). At a median follow-up of 50+ months, 42 patients are alive and well (5 with evidence of disease), and 1 patient in remission died of encephalopathy. Progressive/recurrent disease occurred in 12 patients, 1 stage 2A, 2 stage 2B, 4 stage 3 and 5 stage 4S. Chemotherapy was eventually used in 4 patients: a 3-year-old stage 2B patient who developed stage 4; a 2-year-old whose recurrent tumour had poor-risk biological markers; a 1-year-old whose recurrent stage 3 disease infiltrated a vertebral body and a stage 4S infant with respiratory impairment from progressive hepatomegaly. Three of the treated patients had diploid tumours. We conclude that non-stage 4 is of itself a strong predictor of a favourable outcome. Diploidy, unfavourable histopathology and unresectable tumours were associated with disease progression. However, evolution of local-regional tumour into distant metastatic stage 4 disease is not typical of neuroblastoma.

Biomarkers, Tumor↗
PubMed1997

A rat model of leptomeningeal human neoplastic xenografts.

Leptomeningeal (LM) cancer spread from either a primary brain tumor or a systemic cancer is rapidly fatal. Current therapies are ineffective and highly toxic to normal nervous system tissues. A xenograft model of LM neoplasia in nude rats using a diversity of tumor cell types was established in order to evaluate new treatment strategies and to study the pharmacokinetics and biological effects of treatments administered into the subarachnoid space. Consistent leptomeningeal engraftment and progressive tumor growth was seen after intrathecal injection of 9 of 13 tumor cells lines, including 2 melanomas, 2 neuroblastomas, 2 medulloblastomas, 2 gliomas, and 1 breast cancer. Clinical signs ranged from steady weight loss commencing from the day after tumor implantation to absence of any signs for three weeks until the sudden occurrence of major neurological deficits or death. Pathologic examination showed only leptomeningeal tumor growth with some cell lines and severe parenchymal invasion with others. CSF cytology consistently demonstrated tumor cells in animals with LM disease. Cranial magnetic resonance (MR) following intravenous (i.v.) administration of a contrast agent revealed enhancing lesions one week following melanoma tumor implantation. Reliable ventricular puncture was demonstrated by radiography following intraventricular (IVent) injection of an iodinated contrast material. IVent instillation of saline, albumin, or antibodies did not provoke clinical toxicity or an inflammatory response.

Animals↗
PubMed1997

Pharmacokinetics and acute toxicology of intraventricular 131 I-monoclonal antibody targeting disialoganglioside in non-human primates.

Tumors metastatic to the leptomeninges are often incurable despite current aggressive treatment modalities. Regional therapy by intrathecal administration of monoclonal antibodies (MoAbs) can maximize their concentration to tumor sites while reducing systemic toxicities. Anti-GD2 antibody 3F8 has successfully targeted human neuroectoderm derived tumors. Disialoganglioside GD2 expression in the central nervous system is identical between humans and cynomolgus monkeys. We studied the pharmacokinetics and the acute and subacute toxicities of intraventricular 131I-3F8 in 8 cynomolgus monkeys. Four animals were purposely immunized with intravenous 3F8 administered 2-4 weeks prior to injections. All animals remained clinically stable. Toxicities included weight loss, fever and CSF leukocytosis. One animal developed a left-sided hemiparesis following his seventh injection, presumably due to a local drug accumulation in the setting of an intermittently patent catheter. The estimated radiation dose to the CSF was 19-48 Gy in the immunized monkeys and 19-82 Gy in the nonimmunized monkeys, and to blood was 0.11-0.98 Gy and 0.29-2.03 Gy, respectively. Histopathology revealed chronic reactive changes adjacent to the region of catheter placement and a focal vasculitis in 2 animals. Peripheral blood counts and bone marrow examinations remained normal. Because of the blood-brain barrier, CSF monkey-anti-mouse antibody titers were less than 10 per cent of those in the serum. In contrast to the CSF radioactivity clearance which was similar in all animals, blood clearance was substantially accelerated in 3F8-immunized animals versus controls. Correspondingly, the CSF to blood dose ratio was improved 1.3 to 6.6 fold (mean 3.5). We conclude that intraventricular administration of 131I-3F8 in primates is tolerable. It can deliver very high doses of radiation to the CSF space with minimal toxicity to blood and bone marrow. Serum anti-mouse antibody accelerates the clearance of 131I-3F8 in blood and may improve the therapeutic index.

Animals↗
PubMed1997

Detection of metastatic neuroblastoma in bone marrow: when is routine marrow histology insensitive?

PURPOSE: To measure the sensitivity of histologic examination in detecting metastatic solid tumor in bone marrow. PATIENTS AND METHODS: A total of 145 patients with stage 4 neuroblastoma underwent 840 marrow examinations, each consisting of six sites (four aspirates and two biopsies), from October 1990 to June 1996 at Memorial Sloan-Kettering Cancer Center. Metastasis was detected by either histology (aspirate by Wright-Giemse and biopsy by Hematoxylin-Eosin stains) or immunostaining of aspirates using anti-G(D2) monoclonal antibodies. RESULTS: The absence of tumor by histology at a single marrow site was a poor guarantee of the absence of disease. The number of false-negative sites increased as the percent of G(D2)-positive tumor cells in the marrow decreased: zero of six if tumor cell count was > or = 1%, and approximately six of six sites if < or = 0.003%. Sensitivity was comparable between marrow aspirate and biopsy. A lower bound (LB) for the probability of false-negative histology was calculated from the (1) discordance among the six marrow samplings and (2) comparison with immunofluorescence. When disease was extensive (eg, at diagnosis), the LB was 0.13 and 0.3, respectively. After treatment, it increased to 0.37 and 0.8. Examining multiple marrow sites can decrease the LB to 0.15. However, at least three sites have to be negative at relapse, six at diagnosis, and more than 50 during treatment or off-therapy follow-up. The marginal decrease in the LB by additional samplings rapidly diminished to less than 0.05 after two sites. CONCLUSION: Except at diagnosis and relapse when gross disease is present, marrow sampling by histology has limited sensitivity. Current practice grossly underestimates the true prevalence of marrow disease.

Biomarkers, Tumor↗
PubMed1997

Molecular detection of GAGE expression in peripheral blood and bone marrow: utility as a tumor marker for neuroblastoma.

The GAGE family of tumor-associated antigens is present in a wide spectrum of human tumors but is highly restricted among normal tissues except to the testis. By reverse transcription-PCR, GAGE expression was detected in 55 of 67 neuroblastomas (NBs; 8 of 12 stage 1, 13 of 13 stage 2, 9 of 12 stage 3, 7 of 12 stage 4S, and 18 of 18 stage 4), 5 of 5 Ewing's and peripheral neuroectodermal tumors, and 11 of 11 tumor cell lines (9 NBs, 1 peripheral neuroectodermal tumor, and 1 melanoma). In contrast, 5 of 6 normal tissues (normal testis was positive), 18 of 18 NB-negative bone marrow (BM; 9 normal, 6 non-NB remission, and 3 stage-2 NB), and 9 of 10 NB-negative peripheral blood (PB; 9 normal and 1 stage 2B) were undetectable. In 18 patients with widespread NB under treatment, GAGE expression in paired samples of BM and PB was 89% concordant. Both correlated strongly with disease measured by conventional methods, including marrow histology or immunocytology, bone scan, meta-iodo-benzylguanidine scan, computed tomography/magnetic resonance imaging, and urine vanilly-mandelic acid/homovanillic acid. When serial samples from 14 patients with stage 4 NB were studied, BM from 7 of 7 patients at diagnosis and 14 of 14 patients (25 samples) on treatment were positive for GAGE. Thirteen patients were in continual remission off therapy, and their GAGE expression (12 BM and 9 PB) was undetectable at follow-up. When compared to molecular detection of tyrosine hydroxylase mRNA, GAGE may offer added sensitivity in detecting NB in both BM and PB. The GAGE family of antigens may be potential tumor markers of minimal residual disease.

Antigens, Neoplasm↗
PubMed1996

The p53 gene in pediatric therapy-related leukemia and myelodysplasia.

We investigated the frequency of p53 mutations in 19 pediatric cases of therapy-related leukemia or myelodysplastic syndrome. Eleven children presented with acute myeloid leukemia, one with mixed-lineage leukemia, two with acute lymphoblastic leukemia, and five with myelodysplasia at times ranging from 11 months to 9 years after a primary cancer diagnosis. The primary cancers, which included 11 solid tumors and eight leukemias, were treated with various combinations of DNA topoisomerase II inhibitors, alkylating agents, or irradiation. Leukemic or myelodysplastic marrows were screened for possible mutations by single-strand conformation polymorphism (SSCP) analysis of p53 exons 4 to 8. The only observed mutation was an inherited 2-basepair deletion at codon 209 in exon 6 that would shift the open reading frame, create a premature termination codon, and foreshorten the resultant protein. Prior therapy in this patient included DNA topoisomerase II inhibitors, alkylating agents, and irradiation. The secondary leukemia presented as myelodysplasia with monosomies of chromosomes 5 and 7 and abnormalities of chromosome 17. Although the primary cancer was an embryonal rhabdomyosarcoma and there was a family history of cancer, the case did not fulfill the clinical criteria for Li-Fraumeni syndrome. This study suggests that germline p53 mutations may predispose some children to therapy-related leukemia and myelodysplasia, but that p53 mutations otherwise are infrequent in this setting.

Adolescent↗
PubMed1996

Kinetics of primary tumor regression with chemotherapy: implications for the timing of surgery.

PURPOSE: The kinetics of tumor regression during administration of chemotherapy has relevance to the timing of surgery. The aim of this study was characterization of the time course of primary tumor regression in initially unresectable rhabdomyosarcoma, hepatoblastoma, and neuroblastoma patients. We also estimated the total cell number in the primary tumor at diagnosis. METHODS: Tumor volumes of 24 pediatric patients with either unresectable rhabdomyosarcoma, hepatoblastoma, or neuroblastoma were determined by using computerized three-dimensional reconstruction from serial computed tomography (CT) scans during chemotherapy. Cell densities were calculated by counting cell numbers in high-power fields and dividing by area and section thickness. Cell number at diagnosis was then calculated. RESULTS: Median tumor volumes at diagnosis were 175 cc, 748 cc, and 738 cc for rhabdomyosarcoma, neuroblastoma, and hepatoblastoma, respectively. The median tumor cell counts were 31, 68, and 59 x 10(10) cells/tumor for rhabdomyosarcoma, neuroblastoma, and hepatoblastoma, respectively. The tumor regression was most rapid during the first two cycles, and little change in volume was observed after three cycles. CONCLUSION: Rapid initial reduction in primary tumor volume with chemotherapy was observed in rhabdomyosarcoma, neuroblastoma, and hepatoblastoma. These data suggest that second-look resection may be feasible after two to three cycles of chemotherapy. This hypothesis may be tested by randomizing the timing of second-look surgical intervention.

Adolescent↗
PubMed1996

Comparison of the targeting characteristics of various radioimmunoconjugates for radioimmunotherapy of neuroblastoma: dosimetry calculations incorporating cross-organ beta doses.

To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody-radioisotope combinations should be used to deliver the highest tumor and the lowest normal tissue doses. In a mouse model, tumor and critical organ-absorbed doses delivered by different radioimmunoconjugates were calculated and compared. We used a Medical Internal Radiation Dosimetry (MIRD)-style mouse dosimetry model that incorporates cross-organ beta doses to make refined estimates of the radiation absorbed dose to tissues. Biodistribution data from neuroblastoma xenografted nude mice were used to estimate tumor, organ and bone marrow absorbed dose values for 90Y-3F8, 131I-3F8 and 131I-F(ab')2 fragments. Immunoreactive fractions of the radiolabeled antibodies were comparable. Although tumor uptake of the radioiodinated and radiometal labeled 3F8 was much higher than that of the radioiodinated F(ab')2 fragments (maximum percent injected dose per gram values were 39.4, 33.2 and 20.1 for 131I-3F8, 90Y-3F8 and 131I-F(ab')2, respectively), tumor to nontumor ratios were higher for radioiodinated fragments (with the exception of tumor to kidney ratio). For the minimum tumor dose necessary for complete ablation, the bone marrow received 195, 278 and 401 cGy for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor doses were 50.1, 232 and 992 cGy/MBq for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor to bone marrow dose, which is defined as the therapeutic index, was 21.5, 14.7 and 10.4 for 131I-F(ab')2, 131I-3F8 and 90Y-3F8. 131I-F(ab')2 fragments produced the highest therapeutic index but also the lowest tumor dose for radioimmunotherapy. Radiometal conjugated IgG produced the highest tumor dose but also the lowest therapeutic index.

Animals↗
PubMed1996

Small molecule nerve growth factor analogs image receptors in vivo.

The in vivo targeting efficacy of small molecule analogs of nerve growth factor (NGF) that bind the NGF receptor p140 TrkA was evaluated and compared with that of a high-affinity anti-TrkA monoclonal antibody (Mab 5C3). Nuclear imaging studies were done after the injection of 99mTc-labeled compounds in nude mice bearing tumors. Kinetics of tumor targetting, blood clearance, and bioavailability of NGF mimics were equivalent or better than Mab 5C3. Tumors that do not express TrkA were not targeted, demonstrating the specificity of NGF mimics in vivo. This comparative biodistribution study demonstrates that receptor-specific small molecule analogs designed from large polypeptides may be more useful than antibodies and may be effective agents for the detection, diagnosis, and possible treatment of neoplasias involving overexpressed oncogenic receptors such as TrkA.

3T3 Cells↗
PubMed1996

Survival from locally invasive or widespread neuroblastoma without cytotoxic therapy.

PURPOSE: To test the hypothesis that cytotoxic therapy is not needed at diagnosis to assure the survival of most patients with non-stage 4 neuroblastoma. METHODS: Patients with non-stage 4 disease received no cytotoxic therapy in the absence of N-myc amplification. The International Neuroblastoma Staging System (INSS) was used. RESULTS: Of 84 consecutive patients with previously untreated, newly diagnosed neuroblastoma, 31 (37%) had non-stage 4 disease. All 31 patients initially received no cytotoxic therapy because none of them had N-myc amplification. Nine stage 1 patients are relapse-free. This report focuses on the 22 patients with locally invasive or distant disease: two stage 2A with gross residual tumor postsurgery, 11 stage 2B with ipsilateral or midline lymph node involvement, four stage 3, and five stage 4S. Eight of the 22 patients were older than 1 year. Postsurgery, 13 patients had visible residual disease, and two others had markedly increased urinary catecholamine levels for more than 1 year. Recurrent or enlarging tumors regressed spontaneously (n = 2) or were excised 5 to 39 months after diagnosis (n = 4). One of the latter had chromosome 1p deletions (common in poor-risk neuroblastoma) that were not detected in the patient's original tumor resected 23 months earlier--findings consistent with clonal evolution or multifocal disease. The patient received chemotherapy. All 22 patients are alive 24 to 98 months (median, 64) from diagnosis. CONCLUSION: Our results suggest that non-stage 4 patients without N-myc amplification can be spared cytotoxic therapy because (1) residual postsurgical or recurrent biologically favorable neuroblastoma rarely evolves into lethal stage 4 disease; and (2) neuroblastoma in lymph nodes has no prognostic significance. These findings are remarkable because no other cancer includes subtypes that are curable without therapy to ablate residual disease.

Adolescent↗
PubMed1996

Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy.

PURPOSE: To test intensive alkylator-based therapy in desmoplastic small round-cell tumor (DSRCT). PATIENTS AND METHODS: Patients received the P6 protocol, which has seven courses of chemotherapy. Courses 1, 2, 3, and 6 included cyclophosphamide 4,200 mg/m2, doxorubicin 75 mg/m2, and vincristine (HD-CAV). Courses 4, 5, and 7 consisted of ifosfamide 9 g/m2 and etoposide 500 mg/m2 for previously untreated patients, or ifosfamide 12 g/m2 and etoposide 1,000 mg/m2 for previously treated patients. Courses started after neutrophil counts reached 500/microL and platelet counts reached 100,000/microL. Tumor resection was attempted. Post-P6 treatment options included radiotherapy and a myeloablative regimen of thiotepa (900 mg/m2) plus carboplatin (1,500 mg/m2), with stem-cell rescue. RESULTS: Ten previously untreated and two previously treated patients have completed therapy. The male-to-female ratio was 11:1. Ages were 7 to 22 years (median, 14). The largest masses were infradiaphragmatic (n = 11) or intrathoracic (n = 1). Other findings included serosal implants (n = 11), regional lymph node invasion (n = 8), ascites or pleural effusion (n = 7), and metastases to liver (n = 5), lungs (n = 4), distant lymph nodes (n = 3), spleen (n = 2), and skeleton (n = 2). Tumors uniformly responded to HD-CAV, but there were no complete pathologic responses. One patient died at 1 month from tumor-related Budd-Chiari syndrome. Of seven patients who achieved a complete remission (CR), five remain in CR 9, 12, 13, 33, and 38 months from the start of P6, one patient died of infection at 12 months (autopsy-confirmed CR), and one patient relapsed 4 months off therapy. Of four patients who achieved a partial remission (PR), one remains progression-free at 34 months and three developed progressive disease. Five patients received local radiotherapy: three were not assessable for response, but in two patients, antitumor effect was evident. Four patients received thiotepa/carboplatin: two were in CR and remain so, and two patients had measurable disease that did not respond. CONCLUSION: For control of DSRCT, our experience supports intensive use of HD-CAV, aggressive surgery to resect visible disease, radiotherapy to high-risk sites, and myeloablative chemotherapy with stem-cell rescue in selected cases.

Abdominal Neoplasms↗
PubMed1996

International neuroblastoma staging system stage 1 neuroblastoma: a prospective study and literature review.

PURPOSE: To gain insight into the management of non-metastatic neuroblastoma by examining clinical and biologic features of International Neuroblastoma Staging System (INSS) stage 1 tumors. METHODS: Patients were staged by both the INSS and the Evans staging system and were evaluated for biologic prognostic factors. Patients with INSS stage 1 received no cytotoxic therapy. The literature was reviewed for clinical and biologic data about INSS stage 1. RESULTS: We evaluated 10 consecutive patients (median age, 17.5 months) with INSS stage 1; all remain disease-free (median follow-up duration, > 5 years). Tumors were in the abdomen (n = 6), chest (n = 3), or pelvis (n = 1). Neuroblastoma involved margins of resection in six tumors. Poor-prognostic biologic findings included tumor-cell diploidy (n = 2) and unfavorable Shimada histopathology (n = 2). Two patients were to receive chemotherapy for, respectively, a tumor deemed unresectable and a tumor classified as Evans stage III; second opinions resulted in surgical management alone in each case. Published reports confirm that some INSS stage 1 patients (1) are at risk for overtreatment, and (2) have poor-prognostic biologic findings yet do well. CONCLUSION: Surgery alone suffices for INSS stage 1 neuroblastoma, even if biologic prognostic factors are unfavorable, microscopic disease remains after surgery, and tumor size is suggestive of "advanced-stage" status in other staging systems. Attempts to resect regionally confined neuroblastomas should take precedence over immediate use of cytotoxic therapy; otherwise, some patients may receive chemotherapy or radiotherapy unnecessarily.

Adolescent↗