High-Dose Conformal Radiotherapy Influenced the Pattern of Failure But Did Not Improve Survival in Glioblastoma Multiforme

doi:10.1016/S0360-3016(97)00911-5

International Journal of Radiation OncologyBiologyPhysics

Volume 40, Issue 5, 15 March 1998, Pages 1141-1149

https://doi.org/10.1016/S0360-3016(97)00911-5 Get rights and content

Abstract

Background and Purpose: Although glioblastoma multiforme is clearly radiation-resistant, there is evidence of a dose–dependent response relationship. The purpose of the study was to evaluate the impact of higher dose by rotational multileaf collimator (MLC) conformal radiation therapy.

Materials and Methods: From 1984 to 1995, 38 consecutive cases with intracranial glioblastoma multiforme were treated using the rotational MLC conformal therapy. There were 25 men and 13 women with a median age of 47 years (12–73 years, mean 46.5 years). Median Karnofsky performance score was 80 (30–100, mean 78.2). Median tumor volume was 64 cc (8–800 cc, mean 110.3 cc). All underwent surgical intervention (only biopsy in 1, partial resection in 13, subtotal resection in 21, and gross total resection in 3). Radiation dose to was 60 to 80 Gy (median 68.5 Gy, mean 68.3 Gy) in 21 patients treated before 1990 and 90 Gy in the 17 patients thereafter. Biweekly i.v. chemotherapy was also administered for both arms.

Results: The 1-year, 2-year, 5-year, and 10-year overall survival rates were 75%, 42%, 20%, and 15%, respectively. Univariate analysis showed the initial tumor volume, residual tumor volume, and Karnofsky performance score were statistically significant factors for survival. Only the residual tumor volume was statistically significant by multivariate analysis. The 5-year survival rate of patients with residual tumors of 5 cc or less in volume was as good as 37%. Survival of the 90-Gy Group appeared inferior to that of the Low-Dose Group, though no statistical difference was seen (the 3-year survival was 40% vs. 22%). Local failure was observed in 16 of the 19 recurrences in the Low-Dose Group, whereas it was observed in only 4 of the 13 recurrences in the 90-Gy Group. The difference in pattern of failure was statistically significant. Two patients of the High-Dose Group developed radiation necrosis and one died of it.

Conclusions: The high-dose conformal radiotherapy did not improve survival in the disease, but did change the pattern of failure.

Introduction

The treatment of glioblastoma is still one of the most challenging problems in neuro-oncology. Patients carrying this tumor have a poor prognosis, with a reported median survival time of less than 1 year from the diagnosis 1, 2. Although various approaches have been tried, most commonly a combination of surgical resection followed by radiotherapy with or without chemotherapy, few studies reported improvement of the results of treatment. Interstitial brachytherapy, radiosurgery, intraoperative radiation therapy (IORT), hyperthermia, and novel chemotherapy have been used to try and improve the outcome 3, 4, 5, 6, 7, 8.

Local control is most essential to improve the outcome because local failure is the most common pattern of recurrence [9]. Postoperative radiotherapy has been shown to improve local control rates and prolong survival for glioblastoma when compared with surgery alone [10].

Recent innovations in diagnostic imaging and advanced treatment-planning techniques have impacted the radiotherapy strategy for this radioresistant tumor. Tumor imaging by computed tomography (CT) and, more recently, by magnetic resonance imaging (MRI), have allowed better tumor localization 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23.

Computerized 3-dimensional (3D) conformal radiation therapy (3DCRT) allows high tumor doses to be delivered while reducing the dose to surrounding normal tissues 24, 25, 26, 27, 28, 29, 30, 31, 32. This approach is justified for several reasons. First, there is evidence for a dose–dependent response in glioblastoma for external doses between 50 and 75 Gy 33, 34, 35, 36. Furthermore, Gutin et al. reported a median survival of more than 2 years using doses over 100 Gy with ¹²⁵I implants [4]. Second, Nelson et al. showed that survival tended to decrease with hyperfractionated external-beam doses above 72 Gy, particularly above 80 Gy, most likely from the increased toxity of the higher doses and the use of larger, 2-dimensionally planned treatment fields [37]. Therefore, both local control and treatment toxicity depend not only on the doses delivered, but also on the volume treated, and this depends on the treatment techniques. The use of 3DCRT may improve the therapeutic ratio compared to conventionally planned and administered external radiation.

We have employed dynamic conformal radiotherapy for glioblastoma since 1984. This is a rotational radiation technique in combination with movement of MLC. Each MLC moves independently according to the gantry angle to create a treatment volume confined to the target volume [38]. Using this technique, we have delivered high doses, up to 90 Gy, with minimal complication rates. Here, we report the outcome of rotational conformal therapy and the prognostic factors.

Section snippets

Patients and Tumor Characteristics

From 1984 to 1995, 38 consecutive patients with glioblastoma multiforme were treated at the Department of Radiology, University of Tokyo Hospital, by postoperative radiation using the conformal technique with MLC. The technique was used either for the entire period or a part of the radiotherapy. There were 23 men and 12 women, ranging in age from 12 to 73 years (mean 46.5 years, median 47 years). Karnofsky performance scores ranged from 30 to 100, with an average of 78.2 (median 80). Primary

Survival

The 1-year, 2-year, 5-year, and 10-year survival rates were 75%, 42%, 20%, and 15%, respectively. The 50% survival period was 17 months. The 1-year, 2-year, 5-year, and 10-year regrowth-free survival rates were 28%, 25%, 13%, and 8%, respectively. The 50% regrowth-free survival period was 5 months. Fig. 3, Fig. 4 illustrate the total survival and regrowth -free survival curves, respectively.

Pattern of Recurrence

The tumor recurred locally in 20, in distant brain areas in 2, local+distant brain in 2, and

Discussion

The results were quite favorable when compared with the reported median survival of 8 to 12 months 36, 37, 40. However, with a median age of 47 years and median preoperative enhanced volume of 64 cc, this is a highly selected and favorable patient population. It is mainly because our facility is a center of affiliated hospitals in the Tokyo area and our neurosurgery department collected patients suitable for aggressive operations from them. Therefore, the encouraging survival outcomes cannot be

Acknowledgements

This work was done in the Department of Radiology, University of Tokyo, Tokyo, Japan. This work was supported in part by a grant for Developmental Scientific Research from the Ministry of Education of Japan.

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Clinical InvestigationsHigh-Dose Conformal Radiotherapy Influenced the Pattern of Failure But Did Not Improve Survival in Glioblastoma Multiforme

Abstract

Introduction

Section snippets

Patients and Tumor Characteristics

Survival

Pattern of Recurrence

Discussion

Acknowledgements

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Magn. Reson. Imaging

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Radiother. Oncol.

Int. J. Radiat. Oncol. Biol. Phys.

Med. Dosimetry

Int. J. Radiat. Oncol. Biol. Phys.

Comput. Tomogr.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Neurosurg. Clin. North Am.

Radiother. Oncol.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A Joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study

Cancer

Combined modality therapy of operated astrocytomas grade 3 and 4A prospective multi-center trial of the Scandinavian Glioblastoma Study Group

Cancer

Treatment of malignant gliomas with surgery, intra-arterial infusions of 1-(2-Hydeoxyethyl)chloroethylnitrosourea and radiation therapyA phase II study

Neurosurgery

Radiosurgery as part of the initial management of patients with malignant gliomas

J. Clin. Oncol.

Intraoperative radiation therapy for malignant glioma

Neurol. Med. Chir.

Combined intra-arterial chemotherapy and irradiation of malignant gliomas

Acta Oncol.

Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial

J. Neurosurg.

Clinical Investigations
High-Dose Conformal Radiotherapy Influenced the Pattern of Failure But Did Not Improve Survival in Glioblastoma Multiforme