Skip to main content
Top
Published in: International Journal of Clinical Oncology 3/2013

01-06-2013 | Original Article

Successful treatment of infants with localized neuroblastoma based on their MYCN status

Authors: Tomoko Iehara, Minoru Hamazaki, Tatsuro Tajiri, Yoshifumi Kawano, Michio Kaneko, Hitoshi Ikeda, Hajime Hosoi, Tohru Sugimoto, Tadashi Sawada, Japanese Infantile Neuroblastoma Cooperative Study Group

Published in: International Journal of Clinical Oncology | Issue 3/2013

Login to get access

Abstract

Background

The aim of this study was to evaluate the effectiveness of post-surgical chemotherapy for infants with localized neuroblastoma without MYCN amplification (MNA), and determine whether risk classification using MNA is reasonable.

Methods

Four hundred and fourteen eligible patients were registered between 1998 and 2004. Resectable patients in stage 1 and 2A/2B were treated by surgical resection only. Unresectable patients in stage 3 without MNA received either 6 cycles of regimen A or 3 cycles of regimen A plus 3 cycles of regimen C2; regimen A consisted of low doses of cyclophosphamide and vincristine and regimen C consisted of cyclophosphamide, vincristine and pirarubicin before surgical resection. The resectable and unresectable patients were randomly selected to receive post-surgical chemotherapy. The patients with MNA received intensive chemotherapy regimen D2, consisting of cyclophosphamide, vincristine, pirarubicin and cisplatin, and some of them received high-dose chemotherapy with stem cell transplantation.

Results

The 5-year event-free survival (5-EFS) rates of stage 1 and 2A/2B patients without MNA were 97.2 and 89.0% respectively (p = 0.02). A total of 31 patients in stage 3 without MNA received post-surgical chemotherapy, and 30 patients did not. The 5-EFS rates of these two groups (96.0 and 96.2%, respectively) were not significantly different (p = 0.869). The 5-EFS rate for localized patients with MNA (n = 6) was 50.0%, and that of patients without MNA was 95.0% (p < 0.001).

Conclusion

Post-surgical chemotherapy was therefore unnecessary for localized patients without MNA. This treatment strategy using MNA is considered to be appropriate in infants.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sawada T, Nishi M, Takeda T et al (1998) Mass screening for neuroblastoma in Japan. Med Pediatr Oncol 31:429–434CrossRef Sawada T, Nishi M, Takeda T et al (1998) Mass screening for neuroblastoma in Japan. Med Pediatr Oncol 31:429–434CrossRef
2.
go back to reference Sawada T, Hirayama M, Nakata T et al (1984) Mass screening for neuroblastoma in infants in Japan. Interim report of a mass screening group. Lancet 2:271–273PubMedCrossRef Sawada T, Hirayama M, Nakata T et al (1984) Mass screening for neuroblastoma in infants in Japan. Interim report of a mass screening group. Lancet 2:271–273PubMedCrossRef
3.
go back to reference Hachitanda Y, Ishimoto K, Hata J et al (1994) One hundred neuroblastomas detected through a mass screening system in Japan. Cancer 74:3223–3226PubMedCrossRef Hachitanda Y, Ishimoto K, Hata J et al (1994) One hundred neuroblastomas detected through a mass screening system in Japan. Cancer 74:3223–3226PubMedCrossRef
4.
go back to reference Castleberry RP, Shuster JJ, Altshluer G et al (1992) Infants with neuroblastoma and regional lymph node metastases have a favorable outlook after limited postoperative chemotherapy: a Pediatric Oncology Group Study. J Clin Oncol 10:1299–1304PubMed Castleberry RP, Shuster JJ, Altshluer G et al (1992) Infants with neuroblastoma and regional lymph node metastases have a favorable outlook after limited postoperative chemotherapy: a Pediatric Oncology Group Study. J Clin Oncol 10:1299–1304PubMed
5.
go back to reference Garaventa A, Boni L, Lo Piccolo MS et al (1993) Localized but unresectable neuroblastoma: treatment and outcome of 145 cases. Italian Cooperative Group for Neuroblastoma. J Clin Oncol 1:1770–1779 Garaventa A, Boni L, Lo Piccolo MS et al (1993) Localized but unresectable neuroblastoma: treatment and outcome of 145 cases. Italian Cooperative Group for Neuroblastoma. J Clin Oncol 1:1770–1779
6.
go back to reference Matsumura T, Sawada T, Shikata T et al (1997) Management for neuroblastoma infants in Japan. Korean J Pediatr Hematol Oncol 4:18–28 Matsumura T, Sawada T, Shikata T et al (1997) Management for neuroblastoma infants in Japan. Korean J Pediatr Hematol Oncol 4:18–28
7.
go back to reference Brodeur GM, Pritchrd J Berthold F et al (1993) Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 11:1466–1477PubMed Brodeur GM, Pritchrd J Berthold F et al (1993) Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 11:1466–1477PubMed
8.
go back to reference Shimada H, Umehara S, Monobe Y et al (2001) International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children’s Cancer Group. Cancer 92:2451–2461PubMedCrossRef Shimada H, Umehara S, Monobe Y et al (2001) International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children’s Cancer Group. Cancer 92:2451–2461PubMedCrossRef
9.
go back to reference Brodeur GM, Seeger RC, Schwab M et al (1984) Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224:1121–1124PubMedCrossRef Brodeur GM, Seeger RC, Schwab M et al (1984) Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224:1121–1124PubMedCrossRef
10.
go back to reference Suita S, Tajiri T, Kaneko M et al (2007) Implications of MYCN amplification in patients with stage 4 neuroblastoma who undergo intensive chemotherapy. J Pediatr Surg 42:489–493PubMedCrossRef Suita S, Tajiri T, Kaneko M et al (2007) Implications of MYCN amplification in patients with stage 4 neuroblastoma who undergo intensive chemotherapy. J Pediatr Surg 42:489–493PubMedCrossRef
11.
go back to reference Perez CA, Matthay KK, Atkinson JB et al (2000) Biologic variables in the outcome of stages I and II neuroblastoma treated with surgery as primary therapy: a Children’s Cancer Group Study. J Clin Oncol 18:18–26PubMed Perez CA, Matthay KK, Atkinson JB et al (2000) Biologic variables in the outcome of stages I and II neuroblastoma treated with surgery as primary therapy: a Children’s Cancer Group Study. J Clin Oncol 18:18–26PubMed
12.
go back to reference Alvarado CS, London WB, Look AT et al (2000) Natural history and biology of stage A neuroblastoma: a Pediatric Oncology Group Study. J Pediatr Hematol Oncol 22:197–205PubMedCrossRef Alvarado CS, London WB, Look AT et al (2000) Natural history and biology of stage A neuroblastoma: a Pediatric Oncology Group Study. J Pediatr Hematol Oncol 22:197–205PubMedCrossRef
13.
go back to reference Iehara T, Hosoi H, Akazawa K et al (2006) MYNC gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening. Br J Cancer 94:1510–1515PubMedCrossRef Iehara T, Hosoi H, Akazawa K et al (2006) MYNC gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening. Br J Cancer 94:1510–1515PubMedCrossRef
14.
go back to reference Cohn SL, Pearson AD, London WB et al (2009) The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force Report. J Clin Oncol 27:289–297PubMedCrossRef Cohn SL, Pearson AD, London WB et al (2009) The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force Report. J Clin Oncol 27:289–297PubMedCrossRef
15.
go back to reference Bagatell R, Beck-Popovic M, London WB et al (2009) Significance of MYCN amplification in international neuroblastoma staging system stage 1 and 2 neuroblastoma: a report from the International Neuroblastoma Risk Group database. J Clin Oncol 27:365–370PubMedCrossRef Bagatell R, Beck-Popovic M, London WB et al (2009) Significance of MYCN amplification in international neuroblastoma staging system stage 1 and 2 neuroblastoma: a report from the International Neuroblastoma Risk Group database. J Clin Oncol 27:365–370PubMedCrossRef
16.
go back to reference Simon T, Spitz R, Faldum A et al (2004) New definition of low-risk neuroblastoma using stage, age, and 1p and MYCN status. J Pediatr Hematol Oncol 26:791–796PubMed Simon T, Spitz R, Faldum A et al (2004) New definition of low-risk neuroblastoma using stage, age, and 1p and MYCN status. J Pediatr Hematol Oncol 26:791–796PubMed
17.
go back to reference Rubie H, Cozo C, Plantaz D et al (2003) Localized and neuroblastoma in infants: excellent outcome with low-dose primary chemotherapy. Br J Cancer 89:1605–1609PubMedCrossRef Rubie H, Cozo C, Plantaz D et al (2003) Localized and neuroblastoma in infants: excellent outcome with low-dose primary chemotherapy. Br J Cancer 89:1605–1609PubMedCrossRef
18.
go back to reference De Bernardi B, Conte M, Mancini A et al (1995) Localized resectable neuroblastoma: results of the second study of the Italian Cooperative Group for Neuroblastoma. J Clin Oncol 13:884–893PubMed De Bernardi B, Conte M, Mancini A et al (1995) Localized resectable neuroblastoma: results of the second study of the Italian Cooperative Group for Neuroblastoma. J Clin Oncol 13:884–893PubMed
19.
go back to reference Matthay KK, Perez C, Seeger RC et al (1998) Successful treatment of stage III neuroblastoma based on prospective biologic staging: a Children’s Cancer Group Study. J Clin Oncol 16:1256–1264PubMed Matthay KK, Perez C, Seeger RC et al (1998) Successful treatment of stage III neuroblastoma based on prospective biologic staging: a Children’s Cancer Group Study. J Clin Oncol 16:1256–1264PubMed
20.
go back to reference Cecchetto G, Mosseri V, De Bernardi B et al (2005) Surgical risk factors in primary surgery for localized neuroblastoma: the LNESG1 Study of the European International Society of Pediatric Oncology Neuroblastoma Group. J Clin Oncol 23:8483–8489PubMedCrossRef Cecchetto G, Mosseri V, De Bernardi B et al (2005) Surgical risk factors in primary surgery for localized neuroblastoma: the LNESG1 Study of the European International Society of Pediatric Oncology Neuroblastoma Group. J Clin Oncol 23:8483–8489PubMedCrossRef
21.
go back to reference Shamberger RC, Smith EI, Joshi VV et al (1998) The risk of nephrectomy during local control in abdominal neuroblastoma. J Pediatr Surg 33:161–164PubMedCrossRef Shamberger RC, Smith EI, Joshi VV et al (1998) The risk of nephrectomy during local control in abdominal neuroblastoma. J Pediatr Surg 33:161–164PubMedCrossRef
22.
go back to reference Monclair T, Brodeur GM, Ambros PF et al (2009) The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol 27:298–303PubMedCrossRef Monclair T, Brodeur GM, Ambros PF et al (2009) The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol 27:298–303PubMedCrossRef
23.
go back to reference Tanaka M, Kigasawa H, Kato K et al (2010) A prospective study of a long-term follow-up of an observation program for neuroblastoma detected by mass screening. Pediatr Blood Cancer 54:573–578PubMed Tanaka M, Kigasawa H, Kato K et al (2010) A prospective study of a long-term follow-up of an observation program for neuroblastoma detected by mass screening. Pediatr Blood Cancer 54:573–578PubMed
24.
go back to reference Hero B, Simon T, Spitz R et al (2008) Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. J Clin Oncol 26:1504–1510PubMedCrossRef Hero B, Simon T, Spitz R et al (2008) Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. J Clin Oncol 26:1504–1510PubMedCrossRef
Metadata
Title
Successful treatment of infants with localized neuroblastoma based on their MYCN status
Authors
Tomoko Iehara
Minoru Hamazaki
Tatsuro Tajiri
Yoshifumi Kawano
Michio Kaneko
Hitoshi Ikeda
Hajime Hosoi
Tohru Sugimoto
Tadashi Sawada
Japanese Infantile Neuroblastoma Cooperative Study Group
Publication date
01-06-2013
Publisher
Springer Japan
Published in
International Journal of Clinical Oncology / Issue 3/2013
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-012-0391-y

Other articles of this Issue 3/2013

International Journal of Clinical Oncology 3/2013 Go to the issue

Introduction to Review Articles

Old but new methods in radiation oncology

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine