Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas

Christopher Ryan, Anthony G. Montag, Janet R. Hosenpud, Brian Samuels, James Hayden, Arthur Hung, Atiya Mansoor, Terrance D. Peabody, Arno J. Mundt, Samir Undevia

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

BACKGROUND. The authors studied a dose-intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high-risk soft tissue sarcomas. The primary objective was estimation of the rate of ≥95% pathologic necrosis. METHODS. Twenty-five patients with intermediate-grade or high-grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m 2/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m 2/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted). RESULTS. Sixteen patients (64%) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69%. Twenty-one patients (84%) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40%), ifosfamide-induced encephalopathy (24%), and grade 3/4 anemia (64%). Postoperative wound complications requiring a surgical procedure occurred in 20% of patients. The rate of ≥95% pathologic necrosis was 40% (95% confidence interval [95% CI], 21-59%). Estimates of 2-year overall and disease-free survival were 84% (95% CI, 66-100%) and 62% (95% CI, 37-86%), respectively. CONCLUSIONS. A high rate of ≥95% pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity.

Original languageEnglish (US)
Pages (from-to)2432-2439
Number of pages8
JournalCancer
Volume112
Issue number11
DOIs
StatePublished - Jun 1 2008

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Sarcoma
Epirubicin
Ifosfamide
Radiotherapy
Drug Therapy
Necrosis
Confidence Intervals
National Cancer Institute (U.S.)
Brain Diseases
Chemoradiotherapy
Terminology
Disease-Free Survival
Anemia
Fever
Extremities
Radiation
Wounds and Injuries
Therapeutics

Keywords

  • Chemoradiation
  • Chemotherapy
  • Clinical trial
  • Sarcoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas. / Ryan, Christopher; Montag, Anthony G.; Hosenpud, Janet R.; Samuels, Brian; Hayden, James; Hung, Arthur; Mansoor, Atiya; Peabody, Terrance D.; Mundt, Arno J.; Undevia, Samir.

In: Cancer, Vol. 112, No. 11, 01.06.2008, p. 2432-2439.

Research output: Contribution to journalArticle

Ryan, Christopher ; Montag, Anthony G. ; Hosenpud, Janet R. ; Samuels, Brian ; Hayden, James ; Hung, Arthur ; Mansoor, Atiya ; Peabody, Terrance D. ; Mundt, Arno J. ; Undevia, Samir. / Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas. In: Cancer. 2008 ; Vol. 112, No. 11. pp. 2432-2439.
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abstract = "BACKGROUND. The authors studied a dose-intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high-risk soft tissue sarcomas. The primary objective was estimation of the rate of ≥95{\%} pathologic necrosis. METHODS. Twenty-five patients with intermediate-grade or high-grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m 2/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m 2/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted). RESULTS. Sixteen patients (64{\%}) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69{\%}. Twenty-one patients (84{\%}) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40{\%}), ifosfamide-induced encephalopathy (24{\%}), and grade 3/4 anemia (64{\%}). Postoperative wound complications requiring a surgical procedure occurred in 20{\%} of patients. The rate of ≥95{\%} pathologic necrosis was 40{\%} (95{\%} confidence interval [95{\%} CI], 21-59{\%}). Estimates of 2-year overall and disease-free survival were 84{\%} (95{\%} CI, 66-100{\%}) and 62{\%} (95{\%} CI, 37-86{\%}), respectively. CONCLUSIONS. A high rate of ≥95{\%} pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity.",
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T1 - Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas

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AU - Montag, Anthony G.

AU - Hosenpud, Janet R.

AU - Samuels, Brian

AU - Hayden, James

AU - Hung, Arthur

AU - Mansoor, Atiya

AU - Peabody, Terrance D.

AU - Mundt, Arno J.

AU - Undevia, Samir

PY - 2008/6/1

Y1 - 2008/6/1

N2 - BACKGROUND. The authors studied a dose-intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high-risk soft tissue sarcomas. The primary objective was estimation of the rate of ≥95% pathologic necrosis. METHODS. Twenty-five patients with intermediate-grade or high-grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m 2/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m 2/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted). RESULTS. Sixteen patients (64%) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69%. Twenty-one patients (84%) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40%), ifosfamide-induced encephalopathy (24%), and grade 3/4 anemia (64%). Postoperative wound complications requiring a surgical procedure occurred in 20% of patients. The rate of ≥95% pathologic necrosis was 40% (95% confidence interval [95% CI], 21-59%). Estimates of 2-year overall and disease-free survival were 84% (95% CI, 66-100%) and 62% (95% CI, 37-86%), respectively. CONCLUSIONS. A high rate of ≥95% pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity.

AB - BACKGROUND. The authors studied a dose-intense regimen of epirubicin and ifosfamide with hypofractionated preoperative radiotherapy for high-risk soft tissue sarcomas. The primary objective was estimation of the rate of ≥95% pathologic necrosis. METHODS. Twenty-five patients with intermediate-grade or high-grade, localized soft tissue sarcomas of the extremity or body wall measuring >5 cm were treated with epirubicin at a dose of 30 mg/m 2/day on Days 1 to 4 and ifosfamide at a dose of 2.5 g/m 2/day on Days 1 to 4 every 21 days for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation was administered over 8 fractions during Cycle 2 of preoperative therapy (epirubicin was omitted). RESULTS. Sixteen patients (64%) completed all chemotherapy cycles and the average delivered dose intensity relative to intended therapy was 69%. Twenty-one patients (84%) experienced grade 4 toxicity (using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 2.0]), which was predominantly hematologic. Notable toxicities included neutropenic fever (40%), ifosfamide-induced encephalopathy (24%), and grade 3/4 anemia (64%). Postoperative wound complications requiring a surgical procedure occurred in 20% of patients. The rate of ≥95% pathologic necrosis was 40% (95% confidence interval [95% CI], 21-59%). Estimates of 2-year overall and disease-free survival were 84% (95% CI, 66-100%) and 62% (95% CI, 37-86%), respectively. CONCLUSIONS. A high rate of ≥95% pathologic necrosis was noted with this aggressive chemoradiotherapy regimen. The occurrence of significant acute toxicities limited the delivery of the intended dose intensity.

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