Whole Brain Radiation Therapy Plus Surgical Removal of Single Brain Metastases Improved Patient Outcome
abstracts & commentary
Sources: Patchell RA, et al. Postoperative radiotherapy in the treatment of single metastases to the brain. JAMA 1998;280:1485-1489; Mintz AP, Cairncross JG. Treatment of a single brain metastasis. The role of radiation following surgical resection. JAMA 1998;280:1527-1529. Editorial.
Controversy has surrounded the above sub-ject for more than a decade. Controlled studies indicated that adding whole brain radiation therapy (WBRT) to surgical removal (SR) of single brain metastases improved neurologic outcome, but not length of survival, when compared with the effects of radiation alone. This present, prospective study shows that, within certain limitations, adding WBRT to surgical removal (SR) improves future neurologic outcome, but not length of survival. The policy became theoretically advantageous even before the conclusion of the analysis. A decade ago, when this study started, CT scanning frequently identified single metastases in brains that MRI technology today would identify as having multiple, asymptomatic ones.
This patient group encompassed 95 SR patients with apparently single metastases: 49 received WBRT and 46 did not. Length of survival was calculated from the day of surgical removal to the day of death. Outcome was based on whether patients died from neurological cause or from systemic complications of their malignant disease. At the end of the analysis, 85% of the 95 patients enrolled in the controlled group and 88% in the WBRT group had died. Mean post-operative follow-up on all living patients was similar at 132 weeks, non-WBRT and 127 in the WBRT group (not significant). Mean follow-up times until death after surgical intervention was 43 weeks in the non-WBRT group compared to 48 weeks in the radiated group. Recurrence of tumor, however, was significantly less and more delayed in the WBRT group (n = 9/49 [18%] = P < 0.001) than the non-radiated group (n = 21/46; 46%).
Median survival time in the WBRT group from time of surgery was 48 weeks in 49 SR+WBRT vs. 46 weeks in 46 SR alone. Time between diagnosis of the primary, systemic tumor and the development of brain metastasis was associated with increased survival of all patients who died from neurologic causes. Six out of 43 (14%) had been radiated compared to 17 of 39 (44%; P < 0.003) in the nonradiated group. Despite this terminal advantage, median length of survival from the onset of diagnosed cancer was 48 weeks in the later radiation group vs. 88 weeks in patients not receiving WBRT.
Commentary
Mintz and Cairncross in their editorial accompanying the Patchell article, report that 15-30% of patients with cancer develop cerebral metastases. By the time neurologic abnormalities appear, untreated survival lasts only about a month. Corticosteroids double the time and WBRT may extend it as much as 3-6 months. Variations in protracted radiation technique may somewhat ameliorate neurotoxic symptoms, but the advantage is limited if treatment begins after severe encephalopathy has already occurred. Given the overall survival of 88 weeks in the nonradiated group compared to 48 weeks in those who received WBRT, this may have been an accident of random selection of less severe cancer in the nonradiated patients.
Mintz and Cairncross also bring out nonqualifying arguments against the Patchell inference that all patients with cerebral metastases of systemic cancers need both surgery and radiation therapy. WBRT rarely can be followed by functional independence under these late cancer circumstances and adds additional losses of cognitive function in many single instances. They rarely say, "Is WBRT the right’ choice for all patients whose single brain metastasis has been fully resected but, nevertheless, leaves untouched feelings of fatigue, pain, dementia, and depression?" Indeed, they even ask if resecting brain metastases brings any advantage to patients already stricken by disseminated systemic symptoms and associated declines in quality of life. These are ethical questions that neurologists and their patients need to discuss together before making ultimate decisions.
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