Mahmoud-Ahmed et al. (2002)

Mahmoud-Ahmed et al. (2002)
Design: Retrospective case series (prognosis), evidence level: 3
Country: United States
Inclusion criteria:
Treatment with WBRT only for brain metastases from BC
Exclusion criteria:
Incomplete medical records
Patients undergoing surgical treatment
Treatment with SR
Population:
Number of patients = 116, age range 33 to 99 years, median age = 50 years
Interventions:
112 patients received WBRT by the ‘standard technique’ but 3 patients received WBRT via a ‘German helmet’ and 1 by craniospinal route.

Most patients received a total dose of 3000 cGy in 10 fractions. The median total dose was 3000 cGy (range: 900 – 4500 cGy)

7 patients were given a boost with external beam RT with a median dose of 3900 cGy (range: 3600–4750 cGy)

6 patients discontinued treatment because of deterioration.
Outcomes:
Overall survival (OS) measured from the time of WBRT until time of death or last patient contact, Improvement in KPS as measured by withdrawal from steroid treatment (which was given to all patients prior to WBRT).
Follow up:
Brain metastases were confirmed by use of MRI or CT and these methods were used for follow-up after WBRT. No further details were given.

Only 60/116 patients had at least one follow-up MRI scan by which a treatment response could be assessed. One patient was lost to follow-up altogether.

Cause of death was only determined with certainty in 47 patients of which 10 died of intracranial metastases and 37 of other systemic metastases.
Results:
Median OS for all patients = 4.2 months
OS rate at 1 year = 17%
OS rate at 2 years = 2%

Median OS: KPS < 60 (n = 64) = 1.7 months
Median OS: KPS 70–80 (n = 26) = 4.8 months
Median OS: KPS 90–100 (n = 26) = 8.6 months P = 0.008

Median OS: RPA III (n = 27) = 1.7 months
Median OS: RPA II (n = 78) = 6.1 months
Median OS: RPA I (n = 11) = 8.1 months P = 0.015

Median OS: <3000 cGy (n = 18) = 0.4 months
Median OS: = 3000 cGy (n = 80) = 4.4 months
Median OS: > 3000 cGy (n = 18) = 7.7 months P=0.0001

Symptom relief:
78 patients were withdrawn from steroids after WBRT but re-initiated in 30 patients after the development of new symptoms.

Some patients experienced fatigue, headaches, alopecia, weakness, memory changes and, in one patient, necrosis. 71 patients experienced disease progression either from the primary cancer (n = 16) or systemically (n = 55).

Tumour response (n = 60):
30 patients had failure either locally or with new brain lesions. 5 of these patients received a second course of WBRT and had a median OS of 42 days (range: 0–143) thereafter. 7 patients were treated with intensity-modulated RT or SR and had a median OS of 146 days (range: 7–332) thereafter.

Age, control of primary tumour, control of systemic disease, presence of liver metastases, number of brain metastases, treatment era were not significant prognostic factors for OS. Multivariate analysis showed that KPS was the only significant factor
General comments:
This paper described a large retrospective study of women with breast cancer and brain metastases who received WBRT at a single treatment centre between 1984 and 2000.

79/116 patients had extracranial metastases. 20/162 patients had a single brain metastasis, 38/116 patients had 2–3 lesions, 50/116 had 4–9 lesions and 8/116 patients had more than 9 lesions.

Survival analyses were by the method of Kaplan-Meier. Appropriate statistical methodology was used to analyse the comparisons of survival between sub-groups and the relative contributions to survival of potential prognostic factors.

Data are presented as point estimates and ranges which does not inform about the variance of that data or the statistical significance of conclusions made. The patient numbers are also too low in some sub-groups for comparisons to be statistically sound.

Authors admit to a confounding bias in one sub-group analysis: all the patients who received > 3000 cGy WBRT also had KPS >70, RPA II and controlled primary disease in 72%. This would have probably skewed the results in favour of a longer OS.

From: Chapter 6, Management of specific problems

Cover of Advanced Breast Cancer
Advanced Breast Cancer: Diagnosis and Treatment.
NICE Clinical Guidelines, No. 81.
National Collaborating Centre for Cancer (UK).
Copyright © 2009, National Collaborating Centre for Cancer.

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