|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2003 American Society for Clinical Oncology Impact of Metaiodobenzylguanidine Scintigraphy on Assessing Response of High-Risk Neuroblastoma to Dose-Intensive Induction Chemotherapy
From the Departments of Medical Imaging and Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY. Address reprint requests to Brian H. Kushner, MD, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; email: kushnerb{at}mskcc.org.
Purpose: The International Neuroblastoma Response Criteria (INRC) recommend, but do not make mandatory, metaiodobenzylguanidine (MIBG) scans. We present the first report on the effect of MIBG scans on the classification of response to dose-intensive induction therapy. Patients and Methods: After dose-intensive induction and before consolidative therapy, 162 Memorial Sloan-Kettering Cancer Center (MSKCC) patients with high-risk neuroblastoma (NB) had MIBG scans (99 with 131I, 63 with 123I), computed tomography, 99mTc-bone scan, bone marrow (BM) tests, and urine catecholamine measurements. Induction included high-dose cyclophosphamide (140 mg/kg) plus other agents and high-dose cisplatin (200 mg/m2)/etoposide (600 mg/m2). Results: In 90 patients treated with dose-intensive therapy from diagnosis at MSKCC, the use of MIBG scintigraphy increased the incomplete response numbers from 14 (15.5%) to 20 (22%), giving a complete remission/very good partial remission (CR/VGPR) rate of 78%. In 72 patients treated before referral to MSKCC for intensified therapy, MIBG findings changed the response classification of one patient; the CR/VGPR rate was 43%. MIBG scans showed no BM disease in 15 of 38 patients with histologically evident NB in BM but did show uptake consistent with BM involvement in five patients who had no NB observed in BM tests. Conclusion: With the less effective therapy consequent to the intensification of induction only after initial exposure to standard-dose chemotherapy, MIBG scintigraphy merely confirms the findings of other staging modalities for detection of relatively widespread residual NB. However, when dose-intensive therapy is initiated at diagnosis, the reliable achievement of major disease responses makes extensive BM testing and MIBG scintigraphy prerequisites for accurate determination of disease status.
NEUROBLASTOMA (NB) is one of the most common pediatric extracranial solid tumors,1 arises anywhere from pelvis to neck, produces high urine levels of the catecholamines vanillylmandelic acid (VMA) or homovanillic acid (HVA) in more than 90% of cases, and often metastasizes to bones, bone marrow (BM), lymph nodes, and liver. To assess disease status in patients with this embryonal neoplasm, the International Neuroblastoma Response Criteria (INRC) call for computed tomography (CT), technetium-99m (99mTc)-bone scan, BM histochemical examinations, and measurement of urine catecholamine levels; metaiodobenzylguanidine (MIBG) scintigraphy is recommended, if available.2 Reports covering 16 to 77 patients with all stages of NB have summarized single- or multi-institutional results of pre- and posttreatment MIBG scans.3–18 Some of these reports focused on comparing MIBG scintigraphy with other staging modalities including CT, magnetic resonance imaging, bone scan, BM histology, and catecholamine levels. Characterization of the normal physiological MIBG uptake in children and single photon emission computerized tomography imaging helped reduce the risk of misleading interpretations of MIBG scans.3,19–22 High detection rates were noted for primary and metastatic sites of NB, but MIBG findings had little or no effect on patient treatment. Although recent comprehensive reviews noted a well-established role for MIBG scintigraphy in the staging and monitoring of NB,23,24 uncertainty persists about the utility of routine MIBG scans in the clinical management of NB patients.18,25–28 For example, MIBG scoring systems based on single- or multi-institutional experiences with 27 to 86 stage 4 NB patients have differed about whether the extent of MIBG uptake at diagnosis or after two cycles of chemotherapy does25–27 or does not28 correlate with a good response to induction. Similarly, MIBG uptake in bones after induction and before myeloablative consolidation was an adverse prognostic marker in the experience of the European Bone Marrow Registry29 but not in some single-institutional studies.30,31 The above reports involved retrospective reviews of series of selected patients treated in the 1980s and early 1990s with standard-dose induction chemotherapy. Complete remission/very good partial remission (CR/VGPR) rates of high-risk patients were less than 50%; most patients had readily detectable NB at the end of induction. MIBG findings were confirmatory of other INRC-mandated staging evaluations in the detection of residual disease. More dose-intensive induction regimens have gained widespread usage in recent years because they appear to improve response rates.32–34 This article presents the first report on the impact of MIBG scans on the classification of INRC response to dose-intensive induction therapy. This analysis covers 162 patients, including a series of 90 unselected, newly diagnosed patients and a series of 72 patients referred after receiving one or more cycles of induction chemotherapy elsewhere.
Since 1990, 162 Memorial Sloan-Kettering Cancer Center (MSKCC) patients underwent MIBG scintigraphy to assess response of high-risk NB to dose-intensive induction chemotherapy and before consolidative therapy. High-risk NB was defined as stage 4 in patients more than 1 year old at diagnosis and MYCN-amplified stage 3 and 4S. When diagnosed with high-risk NB, the 99 patients (59% males) imaged by iodine-131 (131I)-MIBG were 4 months to 31 years old (median, 3.92 years), and the 63 patients (48% males) imaged by iodine-123 (123I)-MIBG were 6 months to 34 years old (median, 3.17 years). Six patients had false-negative MIBG scans at diagnosis, 127 patients had MIBG-avid NB documented at or soon after diagnosis, and 29 patients either did not undergo MIBG scintigraphy at diagnosis or had normal MIBG scans first performed after one or more cycles of chemotherapy. In accordance with the INRC2 and MSKCC protocols, the staging evaluation also included CT, 99mTc-bone scan, and urine VMA and HVA levels. BM status was assessed by histochemical examinations of specimens from bilateral posterior and bilateral anterior iliac crests. Informed written consents for tests and treatments were required and obtained in accordance with MSKCC institutional review board rules. First, we compared MIBG scans with other staging modalities (BM histology, 99mTc-bone scan, CT, urine catecholamines). Then, we analyzed results for patients treated from diagnosis at MSKCC (group 1), patients who were referred to MSKCC after receiving one to three cycles of induction elsewhere (group 2, minimally prior-treated patients), and patients who were referred to MSKCC after receiving four or more cycles of chemotherapy elsewhere (group 3, heavily prior-treated patients). MSKCC protocols for high-risk NB included the dose-intensive N6/N7 regimens, which used high-dose cyclophosphamide (140 mg/kg)/doxorubicin (75 mg/m2)/vincristine (0.067 to 0.15 mg/kg), and cisplatin (200 mg/m2)/etoposide (600 mg/m2).34,35 Some prior-treated patients received high-dose cyclophosphamide (140 mg/kg) plus topotecan (6 mg/m2)36 or topotecan (8 mg/m2)/vincristine (0.067 mg/kg). Primary tumors were resected during the period of induction chemotherapy. Disease status was defined by the INRC:2 complete remission (CR) indicates no evidence of NB; very good partial remission (VGPR) indicates primary mass reduced by 90% to 99%, no evidence of distant NB except for skeletal residua, and catecholamines normal; partial remission (PR) indicates more than 50% decrease in measurable disease and one or fewer positive BM site; mixed response (MR) indicates more than 50% decrease of any lesion with less than 50% decrease in any other; no response (NR) indicates less than 50% decrease but less than 25% increase in any existing lesion; and progressive disease (PD) indicates new lesion or more than 25% increase in an existing lesion. MIBG scans were performed with 131I through November 1999 and with 123I thereafter. Patients ingested a solution of potassium iodide (1 gm/mL) to block 131I or 123I uptake by thyroid glands. The dosages per 1.73 m2 body-surface area were 1 mCi (37 MBq) for 131I-MIBG and 10 mCi (370 MBq) for 123I-MIBG scans. Multiple spot images of the entire body were obtained 24 and 48 hours after injection of 131I-MIBG and 24 hours after injection of 123I-MIBG. For bone scans, patients were imaged 2 hours after injection of 99mTc methylene diphosphonate (99mTc-MDP) at 25 mCi (925 MBq) per 70 kg body weight. CT was performed with intravenous and (for abdominal-pelvic imaging) oral contrast. To ensure optimal imaging, young patients were sedated with pentobarbital plus hydroxyzine or diphenhydramine or were placed under general anesthesia with propofol. Scans were read by radiologists who were unaware of the patient’s disease status
Overview CR/VGPR rates were higher in group 1 (78%) and in group 2 (68%) compared with group 3 (30%; Table 1  ). These findings were consistent with an unsatisfactory response to initial therapy as a reason for referral to MSKCC for treatment intensification. Within each group, results were approximately equivalent with 131I-MIBG and 123I-MIBG. For example, in group 3, the CR/VGPR rates were 28% and 31% and the false-negative rates were 28% and 21%, respectively (Table 1).
Osteomedullary Disease MIBG findings and BM histology were discordant for detection of BM disease in 20 (12%) of the 162 patients (Table 2 ). Thus, 15 patients had BM involvement by histology but not by MIBG scans, whereas five patients had MIBG uptake in two or more BM-containing skeletal sites, no morphologic evidence of NB in BM, and normal 99mTc-MDP scans; that is, findings consistent with NB in BM. Overall, 15 (39%) of 38 patients with histologically evident NB in BM had false-negative MIBG scans.
99mTc-MDP scans did not alter the response classification of any patient (except by changing CR to VGPR) (Table 3 ). Specifically, no patient had PD detected by 99mTc-MDP scan alone. In patients with no evidence of NB by BM, CT, and urine tests, normal MIBG findings confirmed a good response (VGPR) to induction despite abnormal (though improved) 99mTc-MDP scans (17 patients). In patients with incomplete responses (ie, PR or less), skeletal MIBG uptake was confirmatory of NB in cortical bone as evidenced by abnormal 99mTc-MDP scan (12 patients) or by CT findings of cranial bone destruction (four patients, all with normal bone scans). One patient with cranial bone and epidural metastases had false-negative 131I-MIBG and 99mTc-MDP scans.
Soft Tissue Disease Of 21 patients with NB in soft tissue proven by biopsy and seen by CT, 14 patients had concordant 131I-MIBG (n = 8) or 123I-MIBG (n = 6) scans, but seven (33%) patients had false-negative studies with 131I-MIBG (n = 5) or 123I-MIBG (n = 2), including one patient with NB in brain.
Urine Catecholamines
Group 1 Results (Patients Treated From Diagnosis at MSKCC) MIBG scans were used to assess response to induction in 90 of 94 consecutive patients in group 1 (Table 1  ). Seventy (78%) patients achieved CR/VGPR. Six (7%) patients—all with no evidence of NB by 99mTc-MDP scan or BM histology—were classified as being in PR (rather than CR/VGPR) solely because of 131I-MIBG (n = 5) or 123I-MIBG (n = 1) uptake: four patients had MIBG uptake in multiple skeletal sites, consistent with BM disease, and two patients had only focal MIBG uptake in skull, consistent with CR in BM but persistence of disease in cranial bones. Six (7%) patients had false-negative studies, including normal 123I-MIBG scans in a patient with PR in BM and in a patient with NB shown by urine results alone, and normal 131I-MIBG scans in single patients with NB shown by CT alone, by CT and urine results, by urine results alone, or by both urine and BM findings. In eight (9%) patients, MIBG positivity (ie, abnormal uptake of 131I-MIBG [n = 6] or 123I-MIBG [n = 2] in soft tissue [n = 4] or bones [n = 4]) confirmed persistence of NB evidenced by other studies and resulted in no change in response classifications: three patients were in PR because of CT findings, two patients in PR had high urine catecholamine levels as the only other evidence of NB (one of these two patients had only focal MIBG uptake in skull bone and the other had multiple sites of MIBG uptake, consistent with BM involvement despite CR in BM by histology), two patients had NR shown by BM histology, and one patient had PD shown by CT.
Group 2 and Group 3 Results (Prior-Treated Patients)
Among the 25 patients in group 2 (Table 1
Among the 47 heavily prior-treated patients in group 3 (Table 1
In patients with high-risk NB completing induction, accurate determination of disease status is critical for judging treatment efficacy, estimating prognosis, and establishing baseline findings for the next phase of therapy. Standardization of response criteria facilitates comparisons between different treatments. Defining disease status in patients with high-risk NB requires a multitude of studies because of its propensity for distant spread. MIBG scintigraphy is increasingly included in the evaluation of NB patients, but its utility for assessing remission status after dose-intensive induction chemotherapy has not previously been reported.
In our 90 group 1 patients (a large, unselected series of consecutively and uniformly treated patients with high-risk NB), the use of MIBG scintigraphy increased the incomplete response numbers from 14 (15.5%) to 20 (22%; Table 1
In contrast, for groups 2 and 3 (patients who received chemotherapy before coming to MSKCC), MIBG scintigraphy played more of a confirmatory role in documenting the persistence of NB. Thus, among the total of 72 prior-treated patients in groups 2 and 3, MIBG findings changed the response classification of only one patient and confirmed the presence of NB in 28 patients (Table 1
Although it commonly substantiated results of other staging studies, MIBG scintigraphy in small numbers of patients in all three groups gave discordant results: false-negative findings or, conversely, detection of NB not otherwise evident. Thus, MIBG scans showed no evidence of BM disease in 15 (39%) of 38 patients with histologically verified NB in BM, but showed uptake consistent with BM metastases in five patients who had no NB seen in BM tests (Table 2 Regarding the detection of NB in BM, two studies noted false-negative MIBG scans in six (23%) of 26 assessments3 and in seven (41%) of 17 assessments;8 these false-negative results matched our experience. Two studies found an advantage to MIBG scintigraphy over BM histology, but one14 of these studies involved only unilateral BM specimens, and the other study10 noted false-negative MIBG scans.
Although 99mTc-MDP scans are useful at diagnosis for adding to the detection rate of cortical bone metastases,9,13,27 our experience indicates that this imaging modality can be dispensed with in the routine follow-up of a clinically responding patient because 99mTc-MDP scans never added to information already provided by MIBG scans (Table 3
Sixty-one percent of the studies in this report involved 131I-MIBG, but we have used 123I-MIBG in recent years because it produces better image quality, requires 2 rather than 3 days, and is less injurious to the thyroid gland.37 Nevertheless, our experience showed no advantage for either isotope in scoring INRC response. For example, the greater sensitivity for detecting NB associated with 123I-MIBG might have been expected to yield a lower response rate, yet the CR/VGPR rate in the group 1 patients was actually higher with 123I-MIBG (81%) than with 131I-MIBG (76%; Table 1 Our data indicate that in the current era of dose-intensive induction therapy for high-risk NB, the reliable achievement of major disease regressions makes comprehensive testing a prerequisite for accurate determination of disease status. Radioimmunoscintigraphy with monoclonal antibodies38,39 and positron emission tomography40 are emerging modalities that can improve disease detection in selected cases. At present, extensive BM tests appear to be the most sensitive means for detecting minimal residual disease, but MIBG scintigraphy yields the only evidence of persistent NB in a small percentage of patients and, therefore, should be required in contemporary clinical trials. Favorable preliminary results with targeted radiotherapy using 131I-MIBG further support the utility of MIBG scintigraphy in patients with high-risk NB.41,42
Supported in part by the Robert Steel Foundation, the Katie’s Find A Cure Fund, and the Justin Zahn Fund, New York, NY.
1. Grovas A, Fremgen A, Rauck A, et al: The National Cancer Data Base report on patterns of childhood cancers in the United States. Cancer 80:2321–2332, 1997[CrossRef][Medline]
2. Brodeur GM, Pritchard J, Berthold F, et al: Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 11:1466–1477, 1993 3. Feine U, Müller-Schauenburg W, Treuner J, et al: Metaiodobenzylguanidine (MIBG) labeled with 123I/131I in neuroblastoma diagnosis and follow-up treatment with a review of the diagnostic results of the International Workshop of Pediatric Oncology held in Rome, September 1986. Med Pediatr Oncol 15:181–187, 1987[Medline] 4. Heyman S, Evans AE, D’Angio GJ: I-131 Metaiodobenzylguanidine: Diagnostic use in neuroblastoma patients in relapse. Med Pediatr Oncol 16:337–340, 1988[Medline] 5. Yeh SDJ, Helson L, Benhua RS: Correlation between iodine-131 MIBG imaging and biological markers in advanced neuroblastoma. Clin Nucl Med 13:46–52, 1988[CrossRef][Medline] 6. Schmiegelow K, Siimes MA, Agertoft L, et al: Radio-iodobenzylguanidine scintigraphy of neuroblastoma: Conflicting results, when compared with standard investigations. Med Pediatr Oncol 17:126–130, 1989 7. Jacobs A, Delree M, Desprechins B, et al: Consolidating the role of *I-MIBG-scintigraphy in childhood neuroblastoma: Five years of clinical experience. Pediatr Radiol 20:157–159, 1990[CrossRef][Medline] 8. Troncone L, Rufini V, Danza FM, et al: Radioiodinated metaiodobenzylguanidine (*I-MIBG) scintigraphy in neuroblastoma. A review of 160 studies. J Nucl Med Allied Sci 34:279–288, 1990[Medline]
9. Gordon I, Peters AM, Gutman A, et al: Skeletal assessment in neuroblastoma—the pitfalls of iodine-123-MIBG scans. J Nucl Med 31:129–134, 1990 10. Corbett R, Olliff J, Fairley N, et al: A prospective comparison between magnetic resonance imaging, metaiodobenzylguanidine scintigraphy and marrow histology/cytology in neuroblastoma. Eur J Cancer 27:1560–1564, 1991[Medline]
11. Shulkin BL, Shapiro B, Hutchinson RJ: Iodine-131-metaiodobenzylguanidine and bone scintigraphy for the detection of neuroblastoma. J Nucl Med 33:1735–1740, 1992 12. Parisi MT, Greene MK, Dykes TM, et al: Efficacy of metaiodobenzylguanidine as a scintigraphic agent for the detection of neuroblastoma. Invest Radiol 27:768–773, 1992[CrossRef][Medline] 13. Turba E, Fagioli G, Mancini AF, et al: Evaluation of stage 4 neuroblastoma patients by means of MIBG and 99mTc-MDP scintigraphy. J Nucl Biol Med 37:107–114, 1993[Medline] 14. Osmanagaoglu K, Lippens M, Benoit Y, et al: A comparison of iodine-123 meta-iodobenzylguanidine scintigraphy and single bone marrow aspiration biopsy in the diagnosis and follow-up of 26 children with neuroblastoma. Eur J Nucl Med 20:1154–1160, 1993[Medline] 15. Lastoria S, Maurea S, Caraco C, et al: Iodine-131 metaiodobenzylguanidine scintigraphy for localization of lesions in children with neuroblastoma: Comparison with computed tomography and ultrasonography. Eur J Nucl Med 20:1161–1167, 1993[Medline] 16. Hadj-Djilani NL, Lebtahi NE, Delaloye AB, et al: Diagnosis and follow-up of neuroblastoma by means of iodine-123 metaiodobenzylguanidine scintigraphy and bone scan, and the influence of histology. Eur J Nucl Med 22:322–329, 1995[CrossRef][Medline] 17. Abrahamsen J, Lyck B, Helgestad J, et al: The impact of 123I-meta-iodobenzylguanidine scintigraphy on diagnostics and follow-up of neuroblastoma. Acta Oncol 34:505–510, 1995[Medline]
18. Andrich MP, Shalaby-Rana E, Movassaghi N, et al: The role of 131 iodine-metaiodobenzylguanidine scanning in the correlative imaging of patients with neuroblastoma. Pediatrics 97:246–250, 1996
19. Paltiel HJ, Gelfand MJ, Elgazzar AH, et al: Neural crest tumors: I-123 MIBG imaging in children. Radiology 190:117–121, 1994
20. Bonnin F, Lumbroso J, Tenenbaum F, et al: Refining interpretation of MIBG scans in children. J Nucl Med 35:803–810, 1994
21. Gelfand MJ, Elgazzar AH, Kriss VM, et al: Iodine-123-MIBG SPECT versus planar imaging in children with neural crest tumors. J Nucl Med 35:1753–1757, 1994
22. Ruffini V, Fisher GA, Shulkin BL, et al: Iodine-123-MIBG imaging of neuroblastoma: Utility of SPECT and delayed imaging. J Nucl Med 37:1464–1468, 1996 23. Gelfand MJ: Meta-iodobenzylguanidine in children. Semin Nucl Med 23:231–242, 1993[CrossRef][Medline]
24. Shulkin BL, Shapiro B: Current concepts on the diagnostic use of MIBG in children. J Nucl Med 39:679–688, 1998 25. Ady N, Zucker J-M, Asselain B, et al: A new 123I-MIBG whole body scan scoring method—application to the prediction of the response of metastases to induction chemotherapy of stage IV neuroblastoma. Eur J Cancer 31A:256–261, 1995[Medline] 26. Suc A, Lumbroso J, Rubie H, et al: Metastatic neuroblastoma in children older than one year: Prognostic significance of the initial metaiodobenzylguanidine scan and proposal for a scoring system. Cancer 77:805–811, 1996[CrossRef][Medline] 27. Perel Y, Conway J, Kletzel M, et al: Clinical impact and prognostic value of metaiodo-benzylguanidine imaging in children with metastatic neuroblastoma. J Pediatr Hematol Oncol 21:13–18, 1999[CrossRef][Medline] 28. Frappaz D, Bonneu A, Chauvot P, et al: Metaiodobenzylguanidine assessment of metastatic neuroblastoma: Observer dependency and chemosensitivity evaluation. Med Pediatr Oncol 34:237–241, 2000[CrossRef][Medline] 29. Ladenstein R, Hartmann O, Pinkerton CR: The role of megatherapy with autologous bone marrow rescue in solid tumours of childhood. Ann Oncol 4:S45–S58, 1993 (suppl 1)
30. Englaro EE, Gelfand MJ, Harris RE, et al: I-131 MIBG imaging after bone marrow transplantation for neuroblastoma. Radiology 182:515–520, 1992 31. Hartmann O, Valteau-Couanet D, Vassal G, et al: Prognostic factors in metastatic neuroblastoma in patients over 1 year of age treated with high-dose chemotherapy and stem cell transplantation: A multi-variate analysis in 218 patients treated in a single institution. Bone Marrow Transplant 23:789–795, 1999[CrossRef][Medline] 32. Pearson ADJ, Craft AW, Pinkerton CR, et al: High-dose rapid schedule chemotherapy for disseminated neuroblastoma. Eur J Cancer 28A:1654–1659, 1992[Medline] 33. Campbell LA, Seeger RC, Harris RE, et al: Escalating dose of continuous infusion chemotherapy for refractory neuroblastoma. J Clin Oncol 11:623–629, 1993[Abstract]
34. Kushner BH, LaQuaglia MP, Bonilla MA, et al: Highly effective induction therapy for stage 4 neuroblastoma in children over one year of age. J Clin Oncol 12:2607–2613, 1994 35. Cheung N-KV, Kushner BH, LaQuaglia M, et al: N7: A novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age. Med Pediatr Oncol 36:227–230, 2001[CrossRef][Medline] 36. Kushner BH, Kramer K, Meyers PA, et al: Pilot study of topotecan and high-dose cyclophosphamide for resistant pediatric solid tumors. Med Pediatr Oncol 35:468–474, 2000[CrossRef][Medline] 37. Shapiro B, Gross MD: Radiochemistry, biochemistry, and kinetics of 131I-metaiodobenzyl-guanidine (MIBG) and of 123I-MIBG: Clinical implications of the use of 123I-MIBG. Med Pediatr Oncol 15:170–177, 1987[Medline]
38. Yeh SDJ, Larson SM, Burch L, et al: Radioimmunodetection of neuroblastoma with iodine-131-3F8: Correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities. J Nucl Med 32:769–776, 1991 39. Reuland P, Geiger L, Thelen MH, et al: Follow-up in neuroblastoma: Comparison of metaiodobenzylguanidine and a chimeric anti-GD2 antibody for detection of tumor relapse and therapy response. J Pediatr Hematol Oncol 23:437–442, 2001[CrossRef][Medline]
40. Kushner BH, Yeung HWD, Larson SM, et al: Extending PET scan utility to high-risk neuroblastoma: 18F-fluorodeoxyglucose positron emission tomography as sole imaging modality in follow-up of patients. J Clin Oncol 19:3397–3405, 2001
41. Matthay KK, DeSantes K, Hasegawa B, et al: Phase I dose escalation of 131I-metaiodo-benzylguanidine with autologous bone marrow support in refractory neuroblastoma. J Clin Oncol 16:229–236, 1998
42. Yanik GA, Levine JE, Matthay KK, et al: Pilot study of iodine-131-metaiodo-benzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma. J Clin Oncol 20:2142–2149, 2002 Submitted July 23, 2002; accepted November 18, 2002. This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
