Reduction of cyclophosphamide dose for patients with subset 2 low-risk rhabdomyosarcoma is associated with an increased risk of recurrence: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group

David O. Walterhouse, Alberto S. Pappo, Jane L Meza, John C. Breneman, Andrea Hayes-Jordan, David M. Parham, Timothy P. Cripe, James R. Anderson, William H. Meyer, Douglas S. Hawkins

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Failure-free survival (FFS) and overall survival (OS) rates were found to improve on Intergroup Rhabdomyosarcoma Study (IRS) IV (IRS-IV) compared with IRS-III for patients with subset 2 (IRS stage 1, group III nonorbit or stage 3, group I/II) low-risk embryonal rhabdomyosarcoma with the addition of cyclophosphamide (total cumulative cyclophosphamide dose of 26.4 g/m2) to the combination of vincristine and dactinomycin (VAC). The goal of Children's Oncology Group ARST0331 for subset 2 low-risk patients was to reduce the total cumulative cyclophosphamide dose without compromising FFS. METHODS: Therapy included 4 cycles of VAC (total cumulative cyclophosphamide dose of 4.8 g/m2) followed by 12 cycles of vincristine and dactinomycin over 46 weeks. Patients with group II or III tumors received radiotherapy, except for girls with group III vaginal tumors who enrolled before September 2009 and achieved a complete response with chemotherapy with or without delayed surgical resection. RESULTS: Among 66 eligible patients who were followed for a median of 3.5 years, there were 20 failures versus 10.53 expected failures. The estimated 3-year FFS and OS rates were 70% (95% confidence interval [95% CI], 57%-80%) and 92% (95% CI, 83%-97%), respectively. The estimated 3-year FFS rate was 57% (95% CI, 33%-75%) for girls with subset 2 genital tract embryonal rhabdomyosarcoma (21 patients) and 77% (95% CI, 61%-87%) for all other subset 2 patients (45 patients) (P =.02). CONCLUSIONS: The authors observed suboptimal FFS among patients with subset 2 low-risk rhabdomyosarcoma using reduced total cyclophosphamide. Eliminating radiotherapy for girls with group III vaginal tumors in combination with reduced total cyclophosphamide appeared to contribute to the suboptimal outcome. Cancer 2017;123:2368–2375.

Original languageEnglish (US)
Pages (from-to)2368-2375
Number of pages8
JournalCancer
Volume123
Issue number12
DOIs
StatePublished - Jun 15 2017

Fingerprint

Rhabdomyosarcoma
Sarcoma
Cyclophosphamide
Recurrence
Embryonal Rhabdomyosarcoma
Confidence Intervals
Survival
Survival Rate
Dactinomycin
Vincristine
Neoplasms
Radiotherapy
Drug Therapy

Keywords

  • chemotherapy
  • cyclophosphamide
  • female genital tract
  • radiotherapy
  • rhabdomyosarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Reduction of cyclophosphamide dose for patients with subset 2 low-risk rhabdomyosarcoma is associated with an increased risk of recurrence : A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. / Walterhouse, David O.; Pappo, Alberto S.; Meza, Jane L; Breneman, John C.; Hayes-Jordan, Andrea; Parham, David M.; Cripe, Timothy P.; Anderson, James R.; Meyer, William H.; Hawkins, Douglas S.

In: Cancer, Vol. 123, No. 12, 15.06.2017, p. 2368-2375.

Research output: Contribution to journalArticle

Walterhouse, David O. ; Pappo, Alberto S. ; Meza, Jane L ; Breneman, John C. ; Hayes-Jordan, Andrea ; Parham, David M. ; Cripe, Timothy P. ; Anderson, James R. ; Meyer, William H. ; Hawkins, Douglas S. / Reduction of cyclophosphamide dose for patients with subset 2 low-risk rhabdomyosarcoma is associated with an increased risk of recurrence : A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. In: Cancer. 2017 ; Vol. 123, No. 12. pp. 2368-2375.
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title = "Reduction of cyclophosphamide dose for patients with subset 2 low-risk rhabdomyosarcoma is associated with an increased risk of recurrence: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group",
abstract = "BACKGROUND: Failure-free survival (FFS) and overall survival (OS) rates were found to improve on Intergroup Rhabdomyosarcoma Study (IRS) IV (IRS-IV) compared with IRS-III for patients with subset 2 (IRS stage 1, group III nonorbit or stage 3, group I/II) low-risk embryonal rhabdomyosarcoma with the addition of cyclophosphamide (total cumulative cyclophosphamide dose of 26.4 g/m2) to the combination of vincristine and dactinomycin (VAC). The goal of Children's Oncology Group ARST0331 for subset 2 low-risk patients was to reduce the total cumulative cyclophosphamide dose without compromising FFS. METHODS: Therapy included 4 cycles of VAC (total cumulative cyclophosphamide dose of 4.8 g/m2) followed by 12 cycles of vincristine and dactinomycin over 46 weeks. Patients with group II or III tumors received radiotherapy, except for girls with group III vaginal tumors who enrolled before September 2009 and achieved a complete response with chemotherapy with or without delayed surgical resection. RESULTS: Among 66 eligible patients who were followed for a median of 3.5 years, there were 20 failures versus 10.53 expected failures. The estimated 3-year FFS and OS rates were 70{\%} (95{\%} confidence interval [95{\%} CI], 57{\%}-80{\%}) and 92{\%} (95{\%} CI, 83{\%}-97{\%}), respectively. The estimated 3-year FFS rate was 57{\%} (95{\%} CI, 33{\%}-75{\%}) for girls with subset 2 genital tract embryonal rhabdomyosarcoma (21 patients) and 77{\%} (95{\%} CI, 61{\%}-87{\%}) for all other subset 2 patients (45 patients) (P =.02). CONCLUSIONS: The authors observed suboptimal FFS among patients with subset 2 low-risk rhabdomyosarcoma using reduced total cyclophosphamide. Eliminating radiotherapy for girls with group III vaginal tumors in combination with reduced total cyclophosphamide appeared to contribute to the suboptimal outcome. Cancer 2017;123:2368–2375.",
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T1 - Reduction of cyclophosphamide dose for patients with subset 2 low-risk rhabdomyosarcoma is associated with an increased risk of recurrence

T2 - A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group

AU - Walterhouse, David O.

AU - Pappo, Alberto S.

AU - Meza, Jane L

AU - Breneman, John C.

AU - Hayes-Jordan, Andrea

AU - Parham, David M.

AU - Cripe, Timothy P.

AU - Anderson, James R.

AU - Meyer, William H.

AU - Hawkins, Douglas S.

PY - 2017/6/15

Y1 - 2017/6/15

N2 - BACKGROUND: Failure-free survival (FFS) and overall survival (OS) rates were found to improve on Intergroup Rhabdomyosarcoma Study (IRS) IV (IRS-IV) compared with IRS-III for patients with subset 2 (IRS stage 1, group III nonorbit or stage 3, group I/II) low-risk embryonal rhabdomyosarcoma with the addition of cyclophosphamide (total cumulative cyclophosphamide dose of 26.4 g/m2) to the combination of vincristine and dactinomycin (VAC). The goal of Children's Oncology Group ARST0331 for subset 2 low-risk patients was to reduce the total cumulative cyclophosphamide dose without compromising FFS. METHODS: Therapy included 4 cycles of VAC (total cumulative cyclophosphamide dose of 4.8 g/m2) followed by 12 cycles of vincristine and dactinomycin over 46 weeks. Patients with group II or III tumors received radiotherapy, except for girls with group III vaginal tumors who enrolled before September 2009 and achieved a complete response with chemotherapy with or without delayed surgical resection. RESULTS: Among 66 eligible patients who were followed for a median of 3.5 years, there were 20 failures versus 10.53 expected failures. The estimated 3-year FFS and OS rates were 70% (95% confidence interval [95% CI], 57%-80%) and 92% (95% CI, 83%-97%), respectively. The estimated 3-year FFS rate was 57% (95% CI, 33%-75%) for girls with subset 2 genital tract embryonal rhabdomyosarcoma (21 patients) and 77% (95% CI, 61%-87%) for all other subset 2 patients (45 patients) (P =.02). CONCLUSIONS: The authors observed suboptimal FFS among patients with subset 2 low-risk rhabdomyosarcoma using reduced total cyclophosphamide. Eliminating radiotherapy for girls with group III vaginal tumors in combination with reduced total cyclophosphamide appeared to contribute to the suboptimal outcome. Cancer 2017;123:2368–2375.

AB - BACKGROUND: Failure-free survival (FFS) and overall survival (OS) rates were found to improve on Intergroup Rhabdomyosarcoma Study (IRS) IV (IRS-IV) compared with IRS-III for patients with subset 2 (IRS stage 1, group III nonorbit or stage 3, group I/II) low-risk embryonal rhabdomyosarcoma with the addition of cyclophosphamide (total cumulative cyclophosphamide dose of 26.4 g/m2) to the combination of vincristine and dactinomycin (VAC). The goal of Children's Oncology Group ARST0331 for subset 2 low-risk patients was to reduce the total cumulative cyclophosphamide dose without compromising FFS. METHODS: Therapy included 4 cycles of VAC (total cumulative cyclophosphamide dose of 4.8 g/m2) followed by 12 cycles of vincristine and dactinomycin over 46 weeks. Patients with group II or III tumors received radiotherapy, except for girls with group III vaginal tumors who enrolled before September 2009 and achieved a complete response with chemotherapy with or without delayed surgical resection. RESULTS: Among 66 eligible patients who were followed for a median of 3.5 years, there were 20 failures versus 10.53 expected failures. The estimated 3-year FFS and OS rates were 70% (95% confidence interval [95% CI], 57%-80%) and 92% (95% CI, 83%-97%), respectively. The estimated 3-year FFS rate was 57% (95% CI, 33%-75%) for girls with subset 2 genital tract embryonal rhabdomyosarcoma (21 patients) and 77% (95% CI, 61%-87%) for all other subset 2 patients (45 patients) (P =.02). CONCLUSIONS: The authors observed suboptimal FFS among patients with subset 2 low-risk rhabdomyosarcoma using reduced total cyclophosphamide. Eliminating radiotherapy for girls with group III vaginal tumors in combination with reduced total cyclophosphamide appeared to contribute to the suboptimal outcome. Cancer 2017;123:2368–2375.

KW - chemotherapy

KW - cyclophosphamide

KW - female genital tract

KW - radiotherapy

KW - rhabdomyosarcoma

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