Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma

R. P. Castleberry, L. E. Kun, J. J. Shuster, G. Altshuler, I. E. Smith, R. Nitschke, M. Wharam, N. McWilliams, V. Joshi, F. A. Hayes

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Abstract

Children older than 1 year of age who have neuroblastoma with complete or partial removal of the primary tumor and positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) are a small but higher-risk subset of patients. To further evaluate the importance of identifying patients with POG stage C neuroblastoma and to assess the efficacy and toxicity of adding concurrent radiation therapy (RT) to chemotherapy (CT) in these children, a randomized study was conducted. Eligible patients received cyclophosphamide 150 mg/m2 orally days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR) every 3 weeks for five courses with or without RT to primary tumor and regional lymph nodes (24 to 30 Gy/16 to 20 fractions). Second-look surgery was advised to evaluate response and to remove residual disease. Continuation therapy alternated CYC/ADR every 3 weeks with cisplatin 90 mg/m2 day 1 followed by teniposide 100 mg/m2 day 3 (CDP/VM) for two courses each. Secondary CT with CDP/VM alone was available for patients not achieving complete response (CR) following induction treatment and second-look surgery. Of 29 eligible patients randomized to CT alone, 13 achieved CR, and nine are disease-free (NED) 1 to 52 months (median, 35 months) off therapy. Twenty-two of 33 eligible cases treated with CT/RT attained CR, and 19 are NED 1 to 77 months (median, 23 months) off therapy. Local and metastatic relapses occurred in both arms. Differences in CR, event-free survival, and survival rates were significant, P = .013, .009, and .008, respectively. Surgical compliance was excellent and complications uncommon. Therapy was tolerable in both groups but hematopoietic toxicity was more common in the CT/RT arm. We conclude that POG stage C neuroblastoma in children older than 1 year of age is a higher-risk group that should be identified, that CT/RT provides superior initial and long-term disease control compared with CT alone in this patient subset, and that the occurrence of metastatic failures in both treatment groups suggests a need for more aggressive chemotherapy.

Original languageEnglish (US)
Pages (from-to)789-795
Number of pages7
JournalJournal of Clinical Oncology
Volume9
Issue number5
DOIs
StatePublished - Jan 1 1991

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Neuroblastoma
Radiotherapy
Pediatrics
Drug Therapy
Second-Look Surgery
Cytidine Diphosphate
Doxorubicin
Therapeutics
Lymph Nodes
Teniposide
Cyclophosphamide
Cisplatin
Compliance
Disease-Free Survival
Neoplasms
Survival Rate
Recurrence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma. / Castleberry, R. P.; Kun, L. E.; Shuster, J. J.; Altshuler, G.; Smith, I. E.; Nitschke, R.; Wharam, M.; McWilliams, N.; Joshi, V.; Hayes, F. A.

In: Journal of Clinical Oncology, Vol. 9, No. 5, 01.01.1991, p. 789-795.

Research output: Contribution to journalArticle

Castleberry, RP, Kun, LE, Shuster, JJ, Altshuler, G, Smith, IE, Nitschke, R, Wharam, M, McWilliams, N, Joshi, V & Hayes, FA 1991, 'Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma', Journal of Clinical Oncology, vol. 9, no. 5, pp. 789-795. https://doi.org/10.1200/JCO.1991.9.5.789
Castleberry, R. P. ; Kun, L. E. ; Shuster, J. J. ; Altshuler, G. ; Smith, I. E. ; Nitschke, R. ; Wharam, M. ; McWilliams, N. ; Joshi, V. ; Hayes, F. A. / Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma. In: Journal of Clinical Oncology. 1991 ; Vol. 9, No. 5. pp. 789-795.
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abstract = "Children older than 1 year of age who have neuroblastoma with complete or partial removal of the primary tumor and positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) are a small but higher-risk subset of patients. To further evaluate the importance of identifying patients with POG stage C neuroblastoma and to assess the efficacy and toxicity of adding concurrent radiation therapy (RT) to chemotherapy (CT) in these children, a randomized study was conducted. Eligible patients received cyclophosphamide 150 mg/m2 orally days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR) every 3 weeks for five courses with or without RT to primary tumor and regional lymph nodes (24 to 30 Gy/16 to 20 fractions). Second-look surgery was advised to evaluate response and to remove residual disease. Continuation therapy alternated CYC/ADR every 3 weeks with cisplatin 90 mg/m2 day 1 followed by teniposide 100 mg/m2 day 3 (CDP/VM) for two courses each. Secondary CT with CDP/VM alone was available for patients not achieving complete response (CR) following induction treatment and second-look surgery. Of 29 eligible patients randomized to CT alone, 13 achieved CR, and nine are disease-free (NED) 1 to 52 months (median, 35 months) off therapy. Twenty-two of 33 eligible cases treated with CT/RT attained CR, and 19 are NED 1 to 77 months (median, 23 months) off therapy. Local and metastatic relapses occurred in both arms. Differences in CR, event-free survival, and survival rates were significant, P = .013, .009, and .008, respectively. Surgical compliance was excellent and complications uncommon. Therapy was tolerable in both groups but hematopoietic toxicity was more common in the CT/RT arm. We conclude that POG stage C neuroblastoma in children older than 1 year of age is a higher-risk group that should be identified, that CT/RT provides superior initial and long-term disease control compared with CT alone in this patient subset, and that the occurrence of metastatic failures in both treatment groups suggests a need for more aggressive chemotherapy.",
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