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Single-Arm Phase II Study of Conformal Radiation Therapy and Temozolomide plus Fractionated Stereotactic Conformal Boost in High-Grade Gliomas

Final Report

Einarmige Phase-II-Studie zur konformalen Strahlentherapie mit Temozolomid plus fraktionierter stereotaktischer konformaler Boostbestrahlung bei höhergradigen Gliomen. Abschlussbericht

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Abstract

Purpose:

To assess survival, local control and toxicity using fractionated stereotactic conformal radiotherapy (FSCRT) boost and temozolomide in high-grade gliomas (HGGs).

Patients and Methods:

Patients affected by HGG, with a CTV1(clinical target volume, representing tumor bed ± residual tumor + a margin of 5 mm) ≤ 8 cm were enrolled into this phase II study. Radiotherapy (RT, total dose 6,940 cGy) was administered using a combination of two different techniques: three-dimensional conformal radiotherapy (3D-CRT, to achieve a dose of 5,040 or 5,940 cGy) and FSCRT boost (19 or 10 Gy) tailored by CTV1diameter (≤ 6 cm and > 6 cm, respectively). Temozolomide (75 mg/m2) was administered during the first 2 or 4 weeks of RT. After the end of RT, temozolomide (150–200 mg/m2) was administered for at least six cycles. The sample size of 41 patients was assessed by the single proportion–powered analysis.

Results:

41 patients (36 with glioblastoma multiforme [GBM] and five with anaplastic astrocytoma [AA]) were enrolled; RTOG neurological toxicities G1–2 and G3 were 12% and 3%, respectively. Two cases of radionecrosis were observed. At a median follow-up of 44 months (range 6–56 months), global and GBM median overall survival (OS) were 30 and 28 months. The 2-year survival rate was significantly better compared to the standard treatment (63% vs. 26.5%; p < 0.00001). Median progression-free survival (PFS) was 11 months, in GBM patients 10 months.

Conclusion:

FSCRT boost plus temozolomide is well tolerated and seems to increase survival compared to the standard treatment in patients with HGG.

Zusammenfassung

Ziel:

Untersuchung von Uberleben, lokaler Tumorkontrolle und Toxizitat einer fraktionierten stereotaktischen konformalen Strahlentherapie (FSCRT) mit Boostbestrahlung in Kombination mit Temozolomid bei hochmalignen Gliomen (HMG).

Patienten und Methodik:

Patienten mit HMG und einem CTV1(klinisches Zielvolumen, d. h. Tumorbett ± Resttumor + einem Sicherheitsabstand von 5 mm) ≤ 8 cm wurden in diese Phase-II-Studie eingeschlossen. Die Strahlentherapie (Gesamtdosis 6 940 cGy) wurde als Kombination aus zwei unterschiedlichen Techniken appliziert: dreidimensionale konformale Strahlentherapie (3D-CRT, um eine Strahlendosis von 5 040 oder 5 940 cGy zu erreichen) und lokale Dosisaufsattigung mit FSCRT-Boost (19 oder 10 Gy), die auf den CTV1-Durchmesser (≤ 6 cm bzw. > 6 cm) zugeschnitten war. Temozolomid (75 mg/m2) wurde wahrend der ersten 2 oder 4 Wochen der Strahlentherapie verabreicht. Nach dem Ende der Strahlentherapie erhielten die Patienten Temozolomid (150–200 mg/m2) fur wenigstens sechs Zyklen. Die Fallzahl wurde mit Hilfe eines einfach-proportionalen Testverfahrens („single proportion-powered analysis“) bei 41 Patienten bestimmt.

Ergebnisse:

41 Patienten (36 mit Glioblastoma multiforme [GBM] und funf mit anaplastischem Astrozytom [AA]) wurden behandelt; Neurotoxizitat gemas RTOG-Skala G1–2 bzw. G3 wurde in 12% bzw. 3% der Patienten beobachtet. Zwei Falle von Radionekrose traten auf. Bei einer mittleren Beobachtungszeit von 44 Monaten (Range 6–56 Monate) lagen die mittlere Gesamt- und die GBM-spezifische Uberlebenszeit (OS) bei 30 und 28 Monaten. Die 2-Jahres-Uberlebensrate war signifikant besser im Vergleich zur Standardbehandlung (63% vs. 26,5%; p < 0.00001). Die mittlere progressionsfreie Uberlebenszeit (PFS) betrug 11 Monate, bei GBM-Patienten 10 Monate.

Schlussfolgerung:

FSCRT-Boostbestrahlung plus Temozolomid wird gut toleriert und scheint im Vergleich zur Standardbehandlung die Uberlebenszeit von Patienten mit HMG zu verbessern.

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Authors and Affiliations

  1. Department of Radiotherapy, Catholic University of the Sacred Heart, Rome, Italy

    Mario Balducci, Giuseppina Apicella, Stefania Manfrida, Alba Fiorentino, Giuseppe Roberto D’Agostino, Vincenzo Frascino, Nicola Dinapoli, Giovanna Mantini, Silvia Chiesa, Vincenzo Valentini & Numa Cellini

  2. Department of Radiotherapy, University Hospital Maggiore della Caritá, Novara, Italy

    Giuseppina Apicella

  3. Department of Neurosurgery, Catholic University of the Sacred Heart, Rome, Italy

    Annunziato Mangiola, Alessio Albanese, Pasquale de Bonis & Carmelo Anile

  4. Department of Physics, Catholic University of the Sacred Heart, Rome, Italy

    Luigi Azario

  5. Department of Radiotherapy, University Hospital Maggiore della Carità, Corso Mazzini 18, 28100, Novara, Italy

    Giuseppina Apicella

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  1. Mario Balducci
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Correspondence to Giuseppina Apicella.

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Balducci, M., Apicella, G., Manfrida, S. et al. Single-Arm Phase II Study of Conformal Radiation Therapy and Temozolomide plus Fractionated Stereotactic Conformal Boost in High-Grade Gliomas. Strahlenther Onkol 186, 558–564 (2010). https://doi.org/10.1007/s00066-010-2101-x

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