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3D Conformal Radiotherapy and Cisplatin for Recurrent Malignant Glioma

Published online by Cambridge University Press:  02 December 2014

Lauren VanderSpek ,
Barbara Fisher ,
Glenn Bauman  and
David Macdonald
Lauren VanderSpek
Affiliation:
The Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
Barbara Fisher
Affiliation:
The Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
Glenn Bauman
Affiliation:
The Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
David Macdonald
Affiliation:
The Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
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Abstract

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Purpose:

To determine the maximum tolerated dose of 3D conformal radiotherapy in combination with Cisplatin for patients with recurrent malignant gliomas.

Methods:

From 1999-2003, nine patients with recurrent malignant glioma received fractionated radiotherapy and Cisplatin (20 mg/m2/d IV on days 1-5) in a Phase I radiation dose escalation trial. Three sequential dose levels were evaluated: 25 Gy, 30 Gy, and 35 Gy, using 5 Gy fractions. All patients received prior external beam radiation (median dose 59.4 (20-60) Gy) and five patients received prior chemotherapy.

Results:

Six male and three female patients were enrolled with a median age of 52 years, and a median Karnofsky performance status score of 70. The median re-irradiated tumor volume was 18.9 (0.1-78.5) cm3 and the median follow-up was 8.8 (3.2-31.2) months. One patient (30 Gy/ 6 fractions) experienced medically reversible acute grade 3 toxicity. A second patient (35 Gy/ 7 fractions) experienced acute grade 2 toxicity and histology showed tumor and radiation effect. A third patient (25 Gy/ 5 fractions) experienced late grade 3 toxicity from radiation necrosis. The radiological responses consisted of complete response (1 patient), partial response (1 patient), and stable disease (2 patients). The median overall survival was 8.8 months (95% CI 8.0-9.9), and the median disease free interval was 2.0 months (95% CI 1.4-4.4). Seven patients received chemotherapy following re-irradiation and Cisplatin.

Conclusion:

The maximum tolerated dose of 3D conformal fractionated radiotherapy was 30 Gy in 6 fractions with low dose Cisplatin, which was well tolerated in terms of acute toxicity for our patient population. This regimen demonstrated only modest efficacy in the treatment of recurrent malignant glioma. Combinations of conformal re-irradiation and other systemic agents may merit investigation. Currently our recommended dose is 30 Gy in 6 fractions for selected patients.

Résumé:

RÉSUMÉ:<span class='italic'><span class='bold'>But</span></span>:

Il s'agit d'une étude visant à déterminer la dose maximale tolérée de radiothérapie conformationnelle 3D en combinaison avec l'administration de cisplatine chez les patients qui présentent une récidive de gliome malin.

<span class='italic'><span class='bold'>Méthodes</span></span>:

Neuf patients présentant une récidive d'un gliome malin ont reçu de la radiothérapie fractionnée et du cisplatine (20 mg/m2/j IV les jours 1 - 5) au cours d'une étude clinique de phase I à dose croissante. Trois niveaux séquentiels de doses ont été évalués : 25 Gy, 30 Gy et 35 Gy, en fractions de 5 Gy. Tous les patients avaient reçu préalablement de la radiothérapie externe (dose médiane 59,4 Gy ; écart de 20 à 60 Gy) et cinq patients avaient reçu de la chimiothérapie.

<span class='italic'><span class='bold'>Résultats</span></span>:

Six hommes et trois femmes, dont l'âge médian était de 52 ans et le score médian à l'échelle de Karnofsky était de 70, ont été inclus dans l'étude. Le volume médian de la tumeur réirradiée était de 18,9 cm (0,1 à 78,5 cm) et la durée médiane du suivi était de 8,8 mois (3,2 à 31,2 mois). Un patient, qui avait reçu 30 Gy/6 fractions, a présenté une toxicité aiguë de grade 3 réversible avec le traitement médical. Un second patient, qui avait reçu 35 Gy/7 fractions, a présenté une toxicité aiguë de grade 2 et à l'examen anatomopathologique on a constaté des phénomènes reliés à la tumeur et à l'irradiation. Un troisième patient, qui avait reçu 25 Gy/5 fractions, a présenté une toxicité tardive de grade 3 causée par la nécrose due à l'irradiation. Les réponses radiologiques étaient les suivantes : réponse complète (1 patient), réponse partielle (1 patient) et maladie stable (2 patients). La survie globale médiane était de 8,8 mois (IC de 95% : 8,0 à 9,9), et la survie médiane sans récidive était de 2,0 mois (IC de 95% : 1,4 à 4,4). Sept patients ont reçu de la chimiothérapie après la réirradiation et du cisplatine.

<span class='italic'><span class='bold'>Conclusion</span></span>:

La dose maximale tolérée de radiothérapie conformationnelle 3D était de 30 Gy en 6 fractions associée à du cisplatine à faible dose. Ce traitement a été bien toléré en ce qui concerne la toxicité aiguë chez nos patients. Ce régime de traitement s'est avéré modestement efficace dans le traitement de la récidive du gliome malin. La combinaison de réirradiation conformationnelle à d'autres agents systémiques mérite d'être étudiée. Nous recommandons actuellement la dose de 30 Gy en 6 fractions chez des patients sélectionnés.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 35 , Issue 1 , March 2008 , pp. 57 - 64
Copyright
Copyright © The Canadian Journal of Neurological 2008

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