Hypofractionated radiotherapy for poor prognosis malignant glioma: matched pair survival analysis with MRC controls

doi:10.1016/S0167-8140(03)00077-X

Radiotherapy and Oncology

Volume 67, Issue 2, May 2003, Pages 177-182

https://doi.org/10.1016/S0167-8140(03)00077-X Get rights and content

Abstract

Purpose: To assess the survival benefit of palliative hypofractionated radiotherapy in patients with poor prognosis high grade glioma by a matched comparison to conventionally treated controls.

Method: Ninety-two elderly and/or disabled patients with high grade glioma with poor prognostic features received palliative partial brain radiotherapy to a dose of 30 Gy in six fractions over 2 weeks. Patients were matched for WHO histological grade, performance status and age from a cohort of patients treated with conventionally fractionated radiotherapy to a dose of 60 Gy in 30 fractions in an Medical Research Council (MRC) BR05 trial.

Results: Patients treated with hypofractionated radiotherapy had a median survival of 5 months with a 1-year survival rate of 12% from diagnosis. The median survival of case-matched controls was estimated to be 2.5–4.5 months longer. Following hypofractionated radiotherapy, Barthel score was improved or remained stable in 68% of patients.

Conclusion: Hypofractionated partial brain radiotherapy is a well-tolerated regimen with palliative benefit. Comparison with matched controls suggests lesser survival benefit than would be obtained with radical radiotherapy. However, this is compensated by lower intensity and duration of irradiation induced side effects. It is postulated that there may not be a significant difference in good quality survival or ‘quality adjusted survival’ between the two regimens and this requires testing in prospective trials.

Introduction

Prognosis in patients with high grade glioma is determined by performance status, age and histological grade. In Radiotherapy and Oncology Group (RTOG) studies, patients aged >50 years with a Karnofsky performance status (KPS) <70 treated with radical radiotherapy had a median survival of 4.6–8.9 months [3]. In the Medical Research Council (MRC) trials, the median survival of patients aged >60 years with a poor performance status (WHO performance status >3) following radical radiotherapy was 7.7 months [10]. Although radiotherapy provides a survival benefit with an overall median survival of 9–12 months, the impact of radical treatment on survival in the different prognostic subgroups is not known [9], [13], [20]. In the palliative situation of poor prognosis patients with high grade glioma, survival gain has to be balanced against treatment morbidity and the effect on quality of life.

Most radical radiotherapy regimes employed in the treatment of high grade glioma are given to high doses over a period of 4–6 weeks. An intensive course of 60 Gy over 6 weeks while providing optimum survival gain [2], [11], [21] may be inappropriate for patients destined to survive 6 months or less, where treatment and its after effects may take up to a third to a half of remaining life. We, therefore, investigated a short palliative regime of 30 Gy in six fractions over 2 weeks reported previously [17]. The regime was well tolerated, convenient and provided effective palliation in patients with poor prognosis high grade glioma. However, the potential survival benefit was not defined. In the absence of a randomised study, we compared the outcome of hypofractionated radiotherapy with a conventional intensive 6 week regimen given in a large multicentre MRC trial [19].

Section snippets

Patients and methods

Between August 1991 and March 1999, 92 patients were treated with palliative radiotherapy at the Royal Marsden Hospital, Sutton. Patients in the initial cohort were treated within a prospective Phase II study; subsequently, treatment became part of routine practice. The study population consisted of older patients and/or those with poor performance status. Selection criteria were defined as all patients with KPS ≤50 alone, patients aged 50–70 years with KPS 50–90 and those aged ≥70 years

Statistical methods

Survival of both cohorts was measured from the start of radiotherapy. Survival rates for the matched hypofractionated and BR05 control patients are presented as simple unstratified.

Kaplan Meier plots: to assess the possible impact of treatment approach, three types of Cox regression analysis were done. A simple unadjusted analysis was performed which compares the overall groups without taking into account matching. Subsequently, an adjusted analysis was performed, in which treatment group was

Hypofractionated radiotherapy

Ninety-two patients were considered for hypofractionated radiotherapy. The median time between surgery and radiotherapy was 27 days. In five patients, radiotherapy was terminated prematurely because of progressive disease (one patient), neurological deterioration (two patients) and early death during the course of radiotherapy (two patients).

Eighty-nine patients had died by the time of analysis with glioma identified as the cause of death in 82 cases, pulmonary emboli in three, cerebrovascular

Discussion

Radiotherapy is the established treatment in patients with malignant glioma with a median survival benefit of 3–6 months [9], [20]. With respect to survival duration, the optimum dose of radiation defined in randomised studies is 60 Gy in 30 fractions given over 6 weeks [2], [11], [21]. While the overall median survival of patients with malignant glioma is in the region of 9–12 months, a subgroup of patients with adverse prognostic features (glioblastoma histology, old age and poor performance

Acknowledgements

The work was supported in part by the Neuro-Oncology Research fund, The Royal Marsden NHS Trust and the Cancer Research UK (formerly Cancer Research Campaign). The work was undertaken by the Royal Marsden NHS Trust who received a proportion of its funding from the NHS Executive; the views expressed are those of the authors and not necessarily those of the NHS Executive. The BR05 trial was funded by the Medical Research Council.

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Hypofractionated radiotherapy for poor prognosis malignant glioma: matched pair survival analysis with MRC controls

Abstract

Introduction

Section snippets

Patients and methods

Statistical methods

Hypofractionated radiotherapy

Discussion

Acknowledgements

Int J Radiat Oncol Biol Phys

Clin Oncol

Clin Oncol

Int J Radiat Oncol Biol Phys

Control Clin Trials

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

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