Julie A Bradley1, Mark L Kayton2, Yueh-Yun Chi3, Douglas S Hawkins4, Jing Tian3, John Breneman5, Suzanne L Wolden6, David Walterhouse7, David A Rodeberg8, Sarah S Donaldson9. 1. Department of Radiation Oncology, University of Florida, Jacksonville, Florida. Electronic address: jbradley@floridaproton.org. 2. Department of Surgery, The Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida. 3. Department of Biostatistics, University of Florida, Gainesville, Florida. 4. Division of Hematology/Oncology, Seattle Children's Hospital, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, Washington. 5. Department of Radiation Oncology, University of Cincinnati Barrett Cancer Center, Cincinnati, Ohio. 6. Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York. 7. Division of Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 8. Department of Surgery, Brody School of Medicine, East Carolina University, Greenville, North Carolina. 9. Department of Radiation Oncology, Stanford University School of Medicine, Stanford Cancer Institute, Stanford, California.
Abstract
PURPOSE: For infants with localized rhabdomyosarcoma who were enrolled on Children's Oncology Group ARST0331 and ARST0531, local therapy guidelines were provided, but adherence was not mandated because of toxicity concerns. We examined adherence to protocol for local therapy guidelines, treatment variations, and outcomes for these patients. METHODS: Children aged ≤24 months who were enrolled on ARST0331 and ARST0531 were evaluated. Data were verified through radiologic, surgical, pathologic, and clinical records. Local therapy was assessed for adherence to protocol guidelines, with variations termed "individualized local therapy." The subdistribution hazards model assessed local failure, the Kaplan-Meier product limit method assessed event-free survival (EFS) and overall survival, and the log-rank test was used to evaluate prognostic impact. RESULTS: The median age of the patients was 14 months, and 124 patients were eligible. Common primary sites were genitourinary (40%), parameningeal (14%), and the extremities (11%). Most patients had unresected disease (group 3, 64%) and embryonal histology (73%). Fifty-eight percent of patients received radiation therapy at a median of week 12 (weeks 1-45). The median radiation dose was 48.6 Gy (30.6-54 Gy). Forty-three percent of patients received individualized local therapy (outside protocol guidelines), typically omission or delay of radiation therapy. Delayed primary excision was performed in 28% at a median of week 14 (weeks 7-34). With a median follow-up of 5.6 years, the 5-year local failure, EFS, and overall survival rates were 24%, 68%, and 82%, respectively. Local failure was significantly higher (35%) in patients receiving individualized local therapy than in patients who received protocol-specified local therapy (16%; P = .02). The site of failure was local in 64% of patients, local and distant in 5%, and distant only in 23%. EFS was significantly higher among patients who were aged 12 to 24 months, had tumors ≤5 cm, had group 1/2 disease, and underwent protocol-specified therapy. CONCLUSIONS: Local recurrence was the predominant pattern of failure and was more common in those receiving individualized local therapy. De-escalation of effective therapies because of concerns about treatment toxicity should be considered cautiously.
PURPOSE: For infants with localized rhabdomyosarcoma who were enrolled on Children's Oncology Group ARST0331 and ARST0531, local therapy guidelines were provided, but adherence was not mandated because of toxicity concerns. We examined adherence to protocol for local therapy guidelines, treatment variations, and outcomes for these patients. METHODS:Children aged ≤24 months who were enrolled on ARST0331 and ARST0531 were evaluated. Data were verified through radiologic, surgical, pathologic, and clinical records. Local therapy was assessed for adherence to protocol guidelines, with variations termed "individualized local therapy." The subdistribution hazards model assessed local failure, the Kaplan-Meier product limit method assessed event-free survival (EFS) and overall survival, and the log-rank test was used to evaluate prognostic impact. RESULTS: The median age of the patients was 14 months, and 124 patients were eligible. Common primary sites were genitourinary (40%), parameningeal (14%), and the extremities (11%). Most patients had unresected disease (group 3, 64%) and embryonal histology (73%). Fifty-eight percent of patients received radiation therapy at a median of week 12 (weeks 1-45). The median radiation dose was 48.6 Gy (30.6-54 Gy). Forty-three percent of patients received individualized local therapy (outside protocol guidelines), typically omission or delay of radiation therapy. Delayed primary excision was performed in 28% at a median of week 14 (weeks 7-34). With a median follow-up of 5.6 years, the 5-year local failure, EFS, and overall survival rates were 24%, 68%, and 82%, respectively. Local failure was significantly higher (35%) in patients receiving individualized local therapy than in patients who received protocol-specified local therapy (16%; P = .02). The site of failure was local in 64% of patients, local and distant in 5%, and distant only in 23%. EFS was significantly higher among patients who were aged 12 to 24 months, had tumors ≤5 cm, had group 1/2 disease, and underwent protocol-specified therapy. CONCLUSIONS: Local recurrence was the predominant pattern of failure and was more common in those receiving individualized local therapy. De-escalation of effective therapies because of concerns about treatment toxicity should be considered cautiously.
Authors: Lynn Million; James Anderson; John Breneman; Douglas S Hawkins; Fran Laurie; Jeff Michalski; David Rodeberg; Moody Wharam; Suzanne Wolden; Sarah S Donaldson Journal: Int J Radiat Oncol Biol Phys Date: 2010-06-18 Impact factor: 7.038
Authors: Gianni Bisogno; Alessia Compostella; Andrea Ferrari; Guido Pastore; Giovanni Cecchetto; Alberto Garaventa; Paolo Indolfi; Luigi De Sio; Modesto Carli Journal: Cancer Date: 2011-07-12 Impact factor: 6.860
Authors: 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 Journal: Cancer Date: 2017-02-17 Impact factor: 6.860
Authors: W M Crist; J R Anderson; J L Meza; C Fryer; R B Raney; F B Ruymann; J Breneman; S J Qualman; E Wiener; M Wharam; T Lobe; B Webber; H M Maurer; S S Donaldson Journal: J Clin Oncol Date: 2001-06-15 Impact factor: 44.544
Authors: David O Walterhouse; Jane L Meza; John C Breneman; Sarah S Donaldson; Andrea Hayes-Jordan; Alberto S Pappo; Carola Arndt; R Beverly Raney; William H Meyer; Douglas S Hawkins Journal: Pediatr Blood Cancer Date: 2011-02-04 Impact factor: 3.167
Authors: Carola A S Arndt; Julie A Stoner; Douglas S Hawkins; David A Rodeberg; Andrea A Hayes-Jordan; Charles N Paidas; David M Parham; Lisa A Teot; Moody D Wharam; John C Breneman; Sarah S Donaldson; James R Anderson; William H Meyer Journal: J Clin Oncol Date: 2009-09-21 Impact factor: 44.544
Authors: Sarah Whittle; Rajkumar Venkatramani; Anton Schönstein; Svetlana D Pack; Rita Alaggio; Christian Vokuhl; Erin R Rudzinski; Anna-Lena Wulf; Angelica Zin; Juliana R Gruver; Michael A Arnold; Johannes H M Merks; Simone Hettmer; Ewa Koscielniak; Frederic G Barr; Douglas S Hawkins; Gianni Bisogno; Monika Sparber-Sauer Journal: Eur J Cancer Date: 2022-04-19 Impact factor: 10.002
Authors: Timothy B Lautz; Yueh-Yun Chi; Minjie Li; Suzanne L Wolden; Dana L Casey; Jonathan C Routh; Candace F Granberg; Odion Binite; Erin R Rudzinski; Douglas S Hawkins; Rajkumar Venkatramani; David A Rodeberg Journal: Cancer Date: 2020-10-20 Impact factor: 6.921
Authors: Sagar R Patel; Caitlin P Hensel; Jiaxian He; Nicolas E Alcalá; James T Kearns; Kris E Gaston; Peter E Clark; Stephen B Riggs Journal: Rare Tumors Date: 2020-12-04
Authors: Hannah D Rees; Nancy K Hills; Amit J Sabnis; Asmin B Tulpule; Tom K Shimotake; Robert E Goldsby Journal: Cancer Rep (Hoboken) Date: 2021-07-13