Increased local failure for patients with intermediate-risk rhabdomyosarcoma on ARST0531

A report from the Children's Oncology Group

Dana L. Casey, Yueh Yun Chi, Sarah S. Donaldson, Douglas S. Hawkins, Jing Tian, Carola A.S. Arndt, David A. Rodeberg, Jonathan C. Routh, Timothy B. Lautz, Abha A. Gupta, Torunn I. Yock, Suzanne L. Wolden

Research output: Contribution to journalArticle

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Abstract

Background: The objective of this study was to evaluate local control for patients with intermediate-risk rhabdomyosarcoma (RMS) treated on Children's Oncology Group (COG) protocol ARST0531. Methods: This study analyzed 424 patients with intermediate-risk RMS. Patients were randomized to chemotherapy with either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC alternating with vincristine and irinotecan. With the goal of improving local control, radiation therapy (RT) was delivered early at week 4 and was concurrent with irinotecan in the experimental arm. Individualized local control plans for children 24 months old or younger were allowed. Local failure on ARST0531 was compared with local failure on the preceding COG intermediate-risk study, D9803. Results: For patients with group I/II alveolar RMS (n = 55), the 5-year cumulative incidence of local failure was 13.4%; for group III alveolar RMS (n = 141), it was 20.2%; and for group III embryonal RMS (n = 228), it was 27.9% (P =.03). Among patients with group III disease, local failure did not differ by histology, site, nodal status, RT modality, or treatment arm. Local failure was worse for a tumor size >5 cm (32.3% vs 16.7%; P =.001). Among patients with group III embryonal RMS, local failure was higher on ARST0531 than D9803 (27.9% vs 19.4%; P =.03). After the exclusion of patients 24 months old or younger or patients who did not receive radiation, local failure remained significantly increased on ARST0531 (P =.02). After adjustments for clinical prognostic factors, event-free survival and overall survival were worse on ARST0531 (P =.004 and P =.05, respectively). Conclusions: Despite interventions designed to enhance local control, local control was inferior on ARST0531 in comparison with D9803. The reason for this is unclear, but it could be the reduced cyclophosphamide dose on ARST0531.

Original languageEnglish (US)
JournalCancer
DOIs
StatePublished - Jan 1 2019

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Rhabdomyosarcoma
irinotecan
Vincristine
Alveolar Rhabdomyosarcoma
Embryonal Rhabdomyosarcoma
Cyclophosphamide
Dactinomycin
Radiotherapy
Disease-Free Survival
Histology
Radiation
Drug Therapy
Survival
Incidence

Keywords

  • clinical trial
  • cyclophosphamide
  • local control
  • radiation therapy
  • rhabdomyosarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Increased local failure for patients with intermediate-risk rhabdomyosarcoma on ARST0531 : A report from the Children's Oncology Group. / Casey, Dana L.; Chi, Yueh Yun; Donaldson, Sarah S.; Hawkins, Douglas S.; Tian, Jing; Arndt, Carola A.S.; Rodeberg, David A.; Routh, Jonathan C.; Lautz, Timothy B.; Gupta, Abha A.; Yock, Torunn I.; Wolden, Suzanne L.

In: Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Casey, DL, Chi, YY, Donaldson, SS, Hawkins, DS, Tian, J, Arndt, CAS, Rodeberg, DA, Routh, JC, Lautz, TB, Gupta, AA, Yock, TI & Wolden, SL 2019, 'Increased local failure for patients with intermediate-risk rhabdomyosarcoma on ARST0531: A report from the Children's Oncology Group', Cancer. https://doi.org/10.1002/cncr.32204
Casey, Dana L. ; Chi, Yueh Yun ; Donaldson, Sarah S. ; Hawkins, Douglas S. ; Tian, Jing ; Arndt, Carola A.S. ; Rodeberg, David A. ; Routh, Jonathan C. ; Lautz, Timothy B. ; Gupta, Abha A. ; Yock, Torunn I. ; Wolden, Suzanne L. / Increased local failure for patients with intermediate-risk rhabdomyosarcoma on ARST0531 : A report from the Children's Oncology Group. In: Cancer. 2019.
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abstract = "Background: The objective of this study was to evaluate local control for patients with intermediate-risk rhabdomyosarcoma (RMS) treated on Children's Oncology Group (COG) protocol ARST0531. Methods: This study analyzed 424 patients with intermediate-risk RMS. Patients were randomized to chemotherapy with either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC alternating with vincristine and irinotecan. With the goal of improving local control, radiation therapy (RT) was delivered early at week 4 and was concurrent with irinotecan in the experimental arm. Individualized local control plans for children 24 months old or younger were allowed. Local failure on ARST0531 was compared with local failure on the preceding COG intermediate-risk study, D9803. Results: For patients with group I/II alveolar RMS (n = 55), the 5-year cumulative incidence of local failure was 13.4{\%}; for group III alveolar RMS (n = 141), it was 20.2{\%}; and for group III embryonal RMS (n = 228), it was 27.9{\%} (P =.03). Among patients with group III disease, local failure did not differ by histology, site, nodal status, RT modality, or treatment arm. Local failure was worse for a tumor size >5 cm (32.3{\%} vs 16.7{\%}; P =.001). Among patients with group III embryonal RMS, local failure was higher on ARST0531 than D9803 (27.9{\%} vs 19.4{\%}; P =.03). After the exclusion of patients 24 months old or younger or patients who did not receive radiation, local failure remained significantly increased on ARST0531 (P =.02). After adjustments for clinical prognostic factors, event-free survival and overall survival were worse on ARST0531 (P =.004 and P =.05, respectively). Conclusions: Despite interventions designed to enhance local control, local control was inferior on ARST0531 in comparison with D9803. The reason for this is unclear, but it could be the reduced cyclophosphamide dose on ARST0531.",
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T1 - Increased local failure for patients with intermediate-risk rhabdomyosarcoma on ARST0531

T2 - A report from the Children's Oncology Group

AU - Casey, Dana L.

AU - Chi, Yueh Yun

AU - Donaldson, Sarah S.

AU - Hawkins, Douglas S.

AU - Tian, Jing

AU - Arndt, Carola A.S.

AU - Rodeberg, David A.

AU - Routh, Jonathan C.

AU - Lautz, Timothy B.

AU - Gupta, Abha A.

AU - Yock, Torunn I.

AU - Wolden, Suzanne L.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: The objective of this study was to evaluate local control for patients with intermediate-risk rhabdomyosarcoma (RMS) treated on Children's Oncology Group (COG) protocol ARST0531. Methods: This study analyzed 424 patients with intermediate-risk RMS. Patients were randomized to chemotherapy with either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC alternating with vincristine and irinotecan. With the goal of improving local control, radiation therapy (RT) was delivered early at week 4 and was concurrent with irinotecan in the experimental arm. Individualized local control plans for children 24 months old or younger were allowed. Local failure on ARST0531 was compared with local failure on the preceding COG intermediate-risk study, D9803. Results: For patients with group I/II alveolar RMS (n = 55), the 5-year cumulative incidence of local failure was 13.4%; for group III alveolar RMS (n = 141), it was 20.2%; and for group III embryonal RMS (n = 228), it was 27.9% (P =.03). Among patients with group III disease, local failure did not differ by histology, site, nodal status, RT modality, or treatment arm. Local failure was worse for a tumor size >5 cm (32.3% vs 16.7%; P =.001). Among patients with group III embryonal RMS, local failure was higher on ARST0531 than D9803 (27.9% vs 19.4%; P =.03). After the exclusion of patients 24 months old or younger or patients who did not receive radiation, local failure remained significantly increased on ARST0531 (P =.02). After adjustments for clinical prognostic factors, event-free survival and overall survival were worse on ARST0531 (P =.004 and P =.05, respectively). Conclusions: Despite interventions designed to enhance local control, local control was inferior on ARST0531 in comparison with D9803. The reason for this is unclear, but it could be the reduced cyclophosphamide dose on ARST0531.

AB - Background: The objective of this study was to evaluate local control for patients with intermediate-risk rhabdomyosarcoma (RMS) treated on Children's Oncology Group (COG) protocol ARST0531. Methods: This study analyzed 424 patients with intermediate-risk RMS. Patients were randomized to chemotherapy with either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC alternating with vincristine and irinotecan. With the goal of improving local control, radiation therapy (RT) was delivered early at week 4 and was concurrent with irinotecan in the experimental arm. Individualized local control plans for children 24 months old or younger were allowed. Local failure on ARST0531 was compared with local failure on the preceding COG intermediate-risk study, D9803. Results: For patients with group I/II alveolar RMS (n = 55), the 5-year cumulative incidence of local failure was 13.4%; for group III alveolar RMS (n = 141), it was 20.2%; and for group III embryonal RMS (n = 228), it was 27.9% (P =.03). Among patients with group III disease, local failure did not differ by histology, site, nodal status, RT modality, or treatment arm. Local failure was worse for a tumor size >5 cm (32.3% vs 16.7%; P =.001). Among patients with group III embryonal RMS, local failure was higher on ARST0531 than D9803 (27.9% vs 19.4%; P =.03). After the exclusion of patients 24 months old or younger or patients who did not receive radiation, local failure remained significantly increased on ARST0531 (P =.02). After adjustments for clinical prognostic factors, event-free survival and overall survival were worse on ARST0531 (P =.004 and P =.05, respectively). Conclusions: Despite interventions designed to enhance local control, local control was inferior on ARST0531 in comparison with D9803. The reason for this is unclear, but it could be the reduced cyclophosphamide dose on ARST0531.

KW - clinical trial

KW - cyclophosphamide

KW - local control

KW - radiation therapy

KW - rhabdomyosarcoma

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