The Third Intergroup Rhabdomyosarcoma Study

William Crist, Edmund A. Gehan, Abdelsalam H. Ragab, Paul S. Dickman, Sarah S. Donaldson, Christopher Fryer, Denman Hammond, Daniel M. Hays, Janice Herrmann, Ruth Heyn, Pat Morris Jones, Walter Lawrence, William Newton, Jorge Ortega, R. Beverly Raney, Frederick B. Ruymann, Melvin Tefft, Bruce Webber, Eugene Wiener, Moody WharamTeresa J. Vietti, Harold M. Maurer

Research output: Contribution to journalArticle

722 Citations (Scopus)

Abstract

Purpose: The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation. Patients and Methods: One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression- free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984). Results: The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% ± 2% v 55% ± 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83% ± 3% v 76% ± 4%; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5- year PFS estimates, 62% ± 3% v 52% ± 3%; P < .01); however, there were no significant differences in outcome among the groups treated in IRS-III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III. Conclusion: Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival.

Original languageEnglish (US)
Pages (from-to)610-630
Number of pages21
JournalJournal of Clinical Oncology
Volume13
Issue number3
DOIs
StatePublished - Mar 1995

Fingerprint

Rhabdomyosarcoma
Disease-Free Survival
Histology
Orbit
Neoplasms
Head
Therapeutics
Survival
Residual Neoplasm
Dactinomycin
Vincristine
Doxorubicin
Cyclophosphamide
Clinical Trials
Biopsy
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Crist, W., Gehan, E. A., Ragab, A. H., Dickman, P. S., Donaldson, S. S., Fryer, C., ... Maurer, H. M. (1995). The Third Intergroup Rhabdomyosarcoma Study. Journal of Clinical Oncology, 13(3), 610-630. https://doi.org/10.1200/JCO.1995.13.3.610

The Third Intergroup Rhabdomyosarcoma Study. / Crist, William; Gehan, Edmund A.; Ragab, Abdelsalam H.; Dickman, Paul S.; Donaldson, Sarah S.; Fryer, Christopher; Hammond, Denman; Hays, Daniel M.; Herrmann, Janice; Heyn, Ruth; Jones, Pat Morris; Lawrence, Walter; Newton, William; Ortega, Jorge; Raney, R. Beverly; Ruymann, Frederick B.; Tefft, Melvin; Webber, Bruce; Wiener, Eugene; Wharam, Moody; Vietti, Teresa J.; Maurer, Harold M.

In: Journal of Clinical Oncology, Vol. 13, No. 3, 03.1995, p. 610-630.

Research output: Contribution to journalArticle

Crist, W, Gehan, EA, Ragab, AH, Dickman, PS, Donaldson, SS, Fryer, C, Hammond, D, Hays, DM, Herrmann, J, Heyn, R, Jones, PM, Lawrence, W, Newton, W, Ortega, J, Raney, RB, Ruymann, FB, Tefft, M, Webber, B, Wiener, E, Wharam, M, Vietti, TJ & Maurer, HM 1995, 'The Third Intergroup Rhabdomyosarcoma Study', Journal of Clinical Oncology, vol. 13, no. 3, pp. 610-630. https://doi.org/10.1200/JCO.1995.13.3.610
Crist W, Gehan EA, Ragab AH, Dickman PS, Donaldson SS, Fryer C et al. The Third Intergroup Rhabdomyosarcoma Study. Journal of Clinical Oncology. 1995 Mar;13(3):610-630. https://doi.org/10.1200/JCO.1995.13.3.610
Crist, William ; Gehan, Edmund A. ; Ragab, Abdelsalam H. ; Dickman, Paul S. ; Donaldson, Sarah S. ; Fryer, Christopher ; Hammond, Denman ; Hays, Daniel M. ; Herrmann, Janice ; Heyn, Ruth ; Jones, Pat Morris ; Lawrence, Walter ; Newton, William ; Ortega, Jorge ; Raney, R. Beverly ; Ruymann, Frederick B. ; Tefft, Melvin ; Webber, Bruce ; Wiener, Eugene ; Wharam, Moody ; Vietti, Teresa J. ; Maurer, Harold M. / The Third Intergroup Rhabdomyosarcoma Study. In: Journal of Clinical Oncology. 1995 ; Vol. 13, No. 3. pp. 610-630.
@article{0c4983c9c4a8439ca3f4420a494b24db,
title = "The Third Intergroup Rhabdomyosarcoma Study",
abstract = "Purpose: The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation. Patients and Methods: One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression- free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984). Results: The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65{\%} ± 2{\%} v 55{\%} ± 2{\%}; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83{\%} ± 3{\%} v 76{\%} ± 4{\%}; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5- year PFS estimates, 62{\%} ± 3{\%} v 52{\%} ± 3{\%}; P < .01); however, there were no significant differences in outcome among the groups treated in IRS-III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III. Conclusion: Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival.",
author = "William Crist and Gehan, {Edmund A.} and Ragab, {Abdelsalam H.} and Dickman, {Paul S.} and Donaldson, {Sarah S.} and Christopher Fryer and Denman Hammond and Hays, {Daniel M.} and Janice Herrmann and Ruth Heyn and Jones, {Pat Morris} and Walter Lawrence and William Newton and Jorge Ortega and Raney, {R. Beverly} and Ruymann, {Frederick B.} and Melvin Tefft and Bruce Webber and Eugene Wiener and Moody Wharam and Vietti, {Teresa J.} and Maurer, {Harold M.}",
year = "1995",
month = "3",
doi = "10.1200/JCO.1995.13.3.610",
language = "English (US)",
volume = "13",
pages = "610--630",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "3",

}

TY - JOUR

T1 - The Third Intergroup Rhabdomyosarcoma Study

AU - Crist, William

AU - Gehan, Edmund A.

AU - Ragab, Abdelsalam H.

AU - Dickman, Paul S.

AU - Donaldson, Sarah S.

AU - Fryer, Christopher

AU - Hammond, Denman

AU - Hays, Daniel M.

AU - Herrmann, Janice

AU - Heyn, Ruth

AU - Jones, Pat Morris

AU - Lawrence, Walter

AU - Newton, William

AU - Ortega, Jorge

AU - Raney, R. Beverly

AU - Ruymann, Frederick B.

AU - Tefft, Melvin

AU - Webber, Bruce

AU - Wiener, Eugene

AU - Wharam, Moody

AU - Vietti, Teresa J.

AU - Maurer, Harold M.

PY - 1995/3

Y1 - 1995/3

N2 - Purpose: The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation. Patients and Methods: One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression- free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984). Results: The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% ± 2% v 55% ± 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83% ± 3% v 76% ± 4%; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5- year PFS estimates, 62% ± 3% v 52% ± 3%; P < .01); however, there were no significant differences in outcome among the groups treated in IRS-III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III. Conclusion: Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival.

AB - Purpose: The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation. Patients and Methods: One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression- free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984). Results: The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% ± 2% v 55% ± 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83% ± 3% v 76% ± 4%; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5- year PFS estimates, 62% ± 3% v 52% ± 3%; P < .01); however, there were no significant differences in outcome among the groups treated in IRS-III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III. Conclusion: Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival.

UR - http://www.scopus.com/inward/record.url?scp=0028964049&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028964049&partnerID=8YFLogxK

U2 - 10.1200/JCO.1995.13.3.610

DO - 10.1200/JCO.1995.13.3.610

M3 - Article

C2 - 7884423

AN - SCOPUS:0028964049

VL - 13

SP - 610

EP - 630

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 3

ER -