A Phase I Dose-Escalation Study (ISIDE-BT-1) of Accelerated IMRT With Temozolomide in Patients With Glioblastoma

Alessio G. Morganti, Mario Balducci, Maurizio Salvati, Vincenzo Esposito, Pantaleo Romanelli, Marica Ferro, Franco Calista, Cinzia Digesù, Gabriella Macchia, Massimo Ianiri, Francesco Deodato, Savino Cilla, Angelo Piermattei, Vincenzo Valentini, Numa Cellini, Gian Paolo Cantore

Research output: Contribution to journalArticle

Abstract

Purpose: To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed ± enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade ≥3 or any hematological toxicity rated as ≥4 by Radiation Therapy Oncology Group (RTOG) criteria. Results: Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. Conclusion: Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.

Original languageEnglish
Pages (from-to)92-97
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume77
Issue number1
DOIs
Publication statusPublished - May 1 2010

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temozolomide
Intensity-Modulated Radiotherapy
Glioblastoma
radiation therapy
dosage
toxicity
planning
margins
grade
Nervous System
Clinical Trials, Phase I
Radiation Oncology
Maximum Tolerated Dose
edema

Keywords

  • Glioblastoma
  • IMRT
  • Phase I
  • Radiotherapy
  • Temozolomide

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

A Phase I Dose-Escalation Study (ISIDE-BT-1) of Accelerated IMRT With Temozolomide in Patients With Glioblastoma. / Morganti, Alessio G.; Balducci, Mario; Salvati, Maurizio; Esposito, Vincenzo; Romanelli, Pantaleo; Ferro, Marica; Calista, Franco; Digesù, Cinzia; Macchia, Gabriella; Ianiri, Massimo; Deodato, Francesco; Cilla, Savino; Piermattei, Angelo; Valentini, Vincenzo; Cellini, Numa; Cantore, Gian Paolo.

In: International Journal of Radiation Oncology Biology Physics, Vol. 77, No. 1, 01.05.2010, p. 92-97.

Research output: Contribution to journalArticle

Morganti, AG, Balducci, M, Salvati, M, Esposito, V, Romanelli, P, Ferro, M, Calista, F, Digesù, C, Macchia, G, Ianiri, M, Deodato, F, Cilla, S, Piermattei, A, Valentini, V, Cellini, N & Cantore, GP 2010, 'A Phase I Dose-Escalation Study (ISIDE-BT-1) of Accelerated IMRT With Temozolomide in Patients With Glioblastoma', International Journal of Radiation Oncology Biology Physics, vol. 77, no. 1, pp. 92-97. https://doi.org/10.1016/j.ijrobp.2009.04.064
Morganti, Alessio G. ; Balducci, Mario ; Salvati, Maurizio ; Esposito, Vincenzo ; Romanelli, Pantaleo ; Ferro, Marica ; Calista, Franco ; Digesù, Cinzia ; Macchia, Gabriella ; Ianiri, Massimo ; Deodato, Francesco ; Cilla, Savino ; Piermattei, Angelo ; Valentini, Vincenzo ; Cellini, Numa ; Cantore, Gian Paolo. / A Phase I Dose-Escalation Study (ISIDE-BT-1) of Accelerated IMRT With Temozolomide in Patients With Glioblastoma. In: International Journal of Radiation Oncology Biology Physics. 2010 ; Vol. 77, No. 1. pp. 92-97.
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abstract = "Purpose: To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed ± enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade ≥3 or any hematological toxicity rated as ≥4 by Radiation Therapy Oncology Group (RTOG) criteria. Results: Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95{\%} of the target volume with the 95{\%} isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. Conclusion: Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.",
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AU - Morganti, Alessio G.

AU - Balducci, Mario

AU - Salvati, Maurizio

AU - Esposito, Vincenzo

AU - Romanelli, Pantaleo

AU - Ferro, Marica

AU - Calista, Franco

AU - Digesù, Cinzia

AU - Macchia, Gabriella

AU - Ianiri, Massimo

AU - Deodato, Francesco

AU - Cilla, Savino

AU - Piermattei, Angelo

AU - Valentini, Vincenzo

AU - Cellini, Numa

AU - Cantore, Gian Paolo

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N2 - Purpose: To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed ± enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade ≥3 or any hematological toxicity rated as ≥4 by Radiation Therapy Oncology Group (RTOG) criteria. Results: Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. Conclusion: Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.

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