Combs et al. (2004)

Combs et al. (2004)
Design: Retrospective case series (prognosis), evidence level: 3
Country: Germany
Inclusion criteria:
None stated
Exclusion criteria:
None stated
Population:
Number of patients = 62
Interventions:
Group I (n = 10): SR. Performed by linear accelerator with 6-MeV or 15-MeV photons. Single doses of between 15 Gy and 20 Gy dependent on tumour size and location

Group II (n = 13): WBRT at doses of between 30 Gy and 40 Gy within 3–4 weeks using conventional fractionation. SR was given as a focal boost within 6 weeks of WBRT and delivered as a single dose of between 10 Gy and 18 Gy.

Group III (n = 39): WBRT with SR as salvage therapy given for recurrence of brain metastases at a dose of 10 Gy to 20 Gy prescribed to the 80% isodose.
Outcomes:
Progression-free interval (PFI), Overall survival (OS), measured from SR to death or end of follow-up, Total survival, measured from first diagnosis of breast cancer to death or end of follow- up.
Follow up:
Median follow-up after SR = 11.5 months

Follow-up visits occurred 6 weeks after treatment and every 3 months thereafter. At these appointments MRI scans were performed and a thorough neurological examination given.

50/62 patients died by the end of follow-up. 48/50 deaths were due to tumour progression and 2 deaths occurred because of pulmonary embolism or pneumonia.
Results:
Median OS after SR = 15 months (range: 1–276)
Median time from primary diagnosis to brain metastases = 47 months (range: 0–216)
Median total survival = 64 months (range: 14–408)

Median total OS: RPA I = 72 months (range: 22–264)
Median total OS: RPA II: 64 months (range: 14–408)
Median total OS: RPA III: 48 months (range: 27–72) nsd

Median OS from SR: RPA I = 9 months
Median OS from SR: RPA II = 6 months
Median OS from SR: RPA III = 19 months

Patients < 40 years had significantly longer OS compared to patients > 40 years (P = 0.04). The number of cerebral metastases did not significantly affect OS.

Patients treated with SR only (group I) showed a significant increase in OS compared with patients given WBRT with SR boost (group II) (P = 0.036).
Median time to local tumour control:
Group I = 6.5 months
Group II = 4 months
Group III = 9 months. nsd between groups I and II

Median time to locoregional tumour control:
Group I = 6.5 months
Group II = 4 months
Group III = 7 months. nsd between groups I and II
General comments:
This paper describes a retrospective study of three groups of patients: one group received SR only, the second received WBRT with SR as a boost and the third group received WBRT with SR as salvage therapy. Patients were treated between January 1986 and January 2003.

14 patients had a single brain lesion. 13 patients had 2–3 brain lesions and 35 patients had ≥ 4 lesions.

14/62 patients had received a surgical resection of a cerebral metastasis prior to RT but none after.

Intermediate risk (RPA I) patients = 34%
High risk (RPA II) patients = 61%
Very high risk (RPA III) patients = 5%

33/62 patients had extracerebral metastases and 29/62 had solitary metastases.

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 association between survival and various prognostic factors.

The authors suggest that WBRT might be omitted in patients with 1–3 brain metastases and progressive cranial disease (i.e. RPA class II). This would mean that chemotherapy (i.e. for advanced breast cancer) might not be delayed as is the case if the patient is receiving WBRT.

The patient numbers in this retrospective review are too low to allow for effective sub-group analyses, particularly with regard to the tumour control between groups I and II which appears to be of no significance. The efficacy of one treatment against another would obviously be better answered by a RCT.

From: Chapter 6, Management of specific problems

Cover of Advanced Breast Cancer
Advanced Breast Cancer: Diagnosis and Treatment.
NICE Clinical Guidelines, No. 81.
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