Radiosurgery versus Surgery, both with Adjuvant Whole Brain Radiotherapy, for Solitary Brain Metastases: A Randomised Controlled Trial

doi:10.1016/j.clon.2011.04.009

Clinical Oncology

Volume 23, Issue 9, November 2011, Pages 646-651

https://doi.org/10.1016/j.clon.2011.04.009 Get rights and content

Abstract

Aims

This randomised non-inferiority trial was designed to assess whether radiosurgery plus adjuvant whole brain radiotherapy (RS + WBRT) is as effective as surgery plus whole brain radiotherapy (S + WBRT) for cancer patients with a solitary brain metastasis, with respect to overall survival and quality of life.

Materials and methods

Major inclusion criteria were a history of systemic cancer within 5 years and enhanced magnetic resonance imaging-confirmed solitary brain metastasis suitable for both radiosurgery and surgery. All patients were to receive WBRT (30 Gy in 10 fractions). Between February 2003 and April 2009, 40 patients were considered eligible, 22 consented to randomisation and 21 were analysed (11 RS + WBRT, 10 S + WBRT). The trial was closed early due to slow accrual.

Results

The estimated median overall survival times for RS + WBRT and S + WBRT patients were 6.2 and 2.8 months, respectively (hazard ratio 0.53, 95% confidence interval 0.20–1.43, P = 0.20). Corresponding median failure-free survival times were 3.1 and 1.7 months (P = 0.20). For 19 ‘per protocol’ patients, 2/10 in the RS + WBRT arm had distant intracranial failure (one also had local failure) and 3/9 S + WBRT patients had distant intracranial failure (no local failures). There were no grade 3–4 late radiation toxicities. Two months after starting treatment there were no significant differences in quality of life between the arms.

Conclusion

This randomised trial encountered the accrual difficulties and consequent low statistical power commonly associated with interdisciplinary studies drawing from a small eligible population, but can contribute to future overviews on the management of solitary brain metastases.

Introduction

Brain metastases occur in 20–40% of cancer patients during the course of their disease and are a frequent cause of morbidity and death. Although the median survival with conventional treatment using corticosteroids and whole brain radiotherapy (WBRT) is 3–6 months, subsets of patients do realise significantly longer survival [1]. Numerous randomised trials have investigated strategies for patients who would be most likely to benefit from aggressive treatment, namely those of good performance status with single or few brain metastases. Such strategies include neurosurgical excision and stereotactic radiosurgery. The median survival times reported for the relatively favourable prognosis patients enrolled in these trials are typically 6–11 months [2].

Non-randomised data have suggested similar benefit from radiosurgery and surgery. However, at the time the current study was conceived, there had been no randomised comparison of these two modalities. This randomised trial was designed to assess whether radiosurgery is as effective as surgery for patients with a solitary brain metastasis when both are combined with adjuvant WBRT. The primary end points were overall survival and health-related quality of life (HRQoL).

Section snippets

Patients

Eligibility criteria required patients to be at least 18 years old with systemic cancer diagnosed within 5 years of registration and a solitary brain metastasis confirmed with enhanced magnetic resonance imaging (MRI) within 2 weeks of the start of treatment. The lesion had to be deemed suitable for both radiosurgery (maximum diameter 40 mm) and surgery (aiming for complete excision) by the Radiosurgery Unit radiation oncologist and neurosurgeon. The Karnofsky performance status (KPS) had to be

Patients

Between 16 February 2003 and 2 April 2009, 40 patients were deemed eligible and offered the trial, 18 of whom declined (Figure 1). Two-thirds of those who did not consent to randomisation were women, the median age was 66 years (range 51–79), and the distribution of primary cancers was similar to the randomised patients. The remaining 22 patients were randomised, but one was subsequently found to be ineligible and excluded (Figure 1).

Clinical features for the 21 eligible randomised patients

Discussion

Clearly, no definitive conclusions can be drawn from this trial due to the small number of patients and consequent low statistical power.

For several reasons, it has proven very difficult to mount randomised trials directly comparing surgery with radiosurgery for brain metastases – the first attempt based at the Harvard Joint Center for Radiation Therapy was abandoned due to slow accrual in 1995 after only seven patients. Although brain metastases are common, less than one third of cases

Conflict of Interest

The authors declare no actual or potential conflicts of interest.

Acknowledgements

The trial was supported by a Royal Australian and New Zealand College of Radiologists Research Grant and by Royal Adelaide Hospital research funding. Neither institution influenced its conduct or reporting in any way. The following clinicians were involved in the care of the trial patients: Martin Borg, Michael Brown, Brian Brophy, Scott Carruthers, Raghu Gowda, Stephen Halcrow, Marguerite Harding, Nigel Jones, Dorothy Keefe, Tim Price, Peter Reilly, Daniel Roos, Stephen Santoreneos, Sid Selva,

References (6)

L. Gaspar et al.
Recursive partitioning analysis (RPA) of prognostic factors in three radiation therapy oncology group (RTOG) brain metastases trials
Int J Radiat Oncol Biol Phys
(1997)
J. Lutterbach et al.
Patients with brain metastases: hope for recursive partitioning analysis (RPA) class 3
Radiother Oncol
(2002)
E. Shaw et al.
Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05
Int J Radiat Oncol Biol Phys
(2000)

There are more references available in the full text version of this article.

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Original ArticleRadiosurgery versus Surgery, both with Adjuvant Whole Brain Radiotherapy, for Solitary Brain Metastases: A Randomised Controlled Trial

Abstract

Aims

Materials and methods

Results

Conclusion

Introduction

Section snippets

Patients

Patients

Discussion

Conflict of Interest

Acknowledgements

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Original Article
Radiosurgery versus Surgery, both with Adjuvant Whole Brain Radiotherapy, for Solitary Brain Metastases: A Randomised Controlled Trial