Treatment options for patients with one to four metastases

WBRT with or without surgical resection.

WBRT with or without stereotactic radiosurgery.

Focal therapy alone (surgical resection or stereotactic radiosurgery).

Three randomized trials examined resection of solitary brain metastases followed by WBRT versus WBRT alone, totaling 195 randomly assigned patients.[7-9] The process that necessarily goes into selecting appropriate patients for surgical resection may account for the small numbers in each trial. In the first trial,[7][Level of evidence B1] performed at a single center, all patients were selected and operated upon by one surgeon.

Three randomized trials examined resection of solitary brain metastases followed by WBRT versus WBRT alone, totaling 195 randomly assigned patients.[7-9] The process that necessarily goes into selecting appropriate patients for surgical resection may account for the small numbers in each trial. In the first trial,[7][Level of evidence B1] performed at a single center, all patients were selected and operated upon by one surgeon.

The first two trials showed an improvement in survival in the surgery group,[7,8] but the third trial showed a trend in favor of the WBRT-only group.[9]

Three randomized trials examined resection of solitary brain metastases followed by WBRT versus WBRT alone, totaling 195 randomly assigned patients.[7-9] The process that necessarily goes into selecting appropriate patients for surgical resection may account for the small numbers in each trial. In the first trial,[7][Level of evidence B1] performed at a single center, all patients were selected and operated upon by one surgeon.

The three trials were combined in a trial-level meta-analysis.[10]

Three randomized trials examined resection of solitary brain metastases followed by WBRT versus WBRT alone, totaling 195 randomly assigned patients.[7-9] The process that necessarily goes into selecting appropriate patients for surgical resection may account for the small numbers in each trial. In the first trial,[7][Level of evidence B1] performed at a single center, all patients were selected and operated upon by one surgeon. › The three trials were combined in a trial-level meta-analysis.[10]

The combined analysis did not show a statistically significant difference in OS (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.34–1.53; P = .4); or in death from neurological causes (relative riskdeath, 0.68; 95% CI, 0.43–1.09; P = .11).[10]

Three randomized trials examined resection of solitary brain metastases followed by WBRT versus WBRT alone, totaling 195 randomly assigned patients.[7-9] The process that necessarily goes into selecting appropriate patients for surgical resection may account for the small numbers in each trial. In the first trial,[7][Level of evidence B1] performed at a single center, all patients were selected and operated upon by one surgeon. › The three trials were combined in a trial-level meta-analysis.[10]

One of the trials reported that combined therapy increased the duration of functionally independent survival.[7][Level of evidence B1]

Three randomized trials examined resection of solitary brain metastases followed by WBRT versus WBRT alone, totaling 195 randomly assigned patients.[7-9] The process that necessarily goes into selecting appropriate patients for surgical resection may account for the small numbers in each trial. In the first trial,[7][Level of evidence B1] performed at a single center, all patients were selected and operated upon by one surgeon. › The three trials were combined in a trial-level meta-analysis.[10]

None of the trials assessed or reported quality of life.

The need for WBRT after resection of solitary brain metastases has been studied.[11] Patients were randomly assigned to either undergo postoperative WBRT or receive no further treatment after resection.

The need for WBRT after resection of solitary brain metastases has been studied.[11] Patients were randomly assigned to either undergo postoperative WBRT or receive no further treatment after resection.

Patients in the WBRT group were less likely to have tumor progression in the brain and were significantly less likely to die of neurological causes.

The need for WBRT after resection of solitary brain metastases has been studied.[11] Patients were randomly assigned to either undergo postoperative WBRT or receive no further treatment after resection.

OS was the same in each group, and there was no difference in duration of functional independence.

One additional randomized study of observation versus WBRT after either surgery or stereotactic radiosurgery for solitary brain metastases was closed after 19 patients had been entered because of slow accrual; therefore, little can be deduced from the trial.[12]

A Radiation Therapy Oncology Group (RTOG) study (RTOG-9508) randomly assigned 333 patients with one to three metastases with a maximum diameter of 4 cm to WBRT (37.5 Gy over 3 weeks) with or without a stereotactic boost.[13] Patients with active systemic disease requiring therapy were excluded. The primary end point was OS with predefined hypotheses in both the full study population and the 186 patients with a solitary metastasis (and no statistical adjustment of P values for the two separate hypotheses).[13][Levels of evidence B1 for the full study population and A1 for patients with solitary metastases]

A Radiation Therapy Oncology Group (RTOG) study (RTOG-9508) randomly assigned 333 patients with one to three metastases with a maximum diameter of 4 cm to WBRT (37.5 Gy over 3 weeks) with or without a stereotactic boost.[13] Patients with active systemic disease requiring therapy were excluded. The primary end point was OS with predefined hypotheses in both the full study population and the 186 patients with a solitary metastasis (and no statistical adjustment of P values for the two separate hypotheses).[13][Levels of evidence B1 for the full study population and A1 for patients with solitary metastases]

Mean OS in the combined-therapy group was 5.7 months, and mean OS in the WBRT-alone group was 6.5 months (P = .14).

A Radiation Therapy Oncology Group (RTOG) study (RTOG-9508) randomly assigned 333 patients with one to three metastases with a maximum diameter of 4 cm to WBRT (37.5 Gy over 3 weeks) with or without a stereotactic boost.[13] Patients with active systemic disease requiring therapy were excluded. The primary end point was OS with predefined hypotheses in both the full study population and the 186 patients with a solitary metastasis (and no statistical adjustment of P values for the two separate hypotheses).[13][Levels of evidence B1 for the full study population and A1 for patients with solitary metastases] › Mean OS in the combined-therapy group was 5.7 months, and mean OS in the WBRT-alone group was 6.5 months (P = .14).

In the subgroup with solitary metastases, OS was better in the combined-therapy group (6.5 months vs. 4.9 months; P = .039 in univariate analysis; P = .053 in a multivariable analysis adjusting for baseline prognostic factors).

A Radiation Therapy Oncology Group (RTOG) study (RTOG-9508) randomly assigned 333 patients with one to three metastases with a maximum diameter of 4 cm to WBRT (37.5 Gy over 3 weeks) with or without a stereotactic boost.[13] Patients with active systemic disease requiring therapy were excluded. The primary end point was OS with predefined hypotheses in both the full study population and the 186 patients with a solitary metastasis (and no statistical adjustment of P values for the two separate hypotheses).[13][Levels of evidence B1 for the full study population and A1 for patients with solitary metastases] › Mean OS in the combined-therapy group was 5.7 months, and mean OS in the WBRT-alone group was 6.5 months (P = .14).

In patients with multiple metastases, survival was 5.8 months in the combined-therapy group versus 6.7 months in the WBRT-only group (P = .98).

A Radiation Therapy Oncology Group (RTOG) study (RTOG-9508) randomly assigned 333 patients with one to three metastases with a maximum diameter of 4 cm to WBRT (37.5 Gy over 3 weeks) with or without a stereotactic boost.[13] Patients with active systemic disease requiring therapy were excluded. The primary end point was OS with predefined hypotheses in both the full study population and the 186 patients with a solitary metastasis (and no statistical adjustment of P values for the two separate hypotheses).[13][Levels of evidence B1 for the full study population and A1 for patients with solitary metastases] › Mean OS in the combined-therapy group was 5.7 months, and mean OS in the WBRT-alone group was 6.5 months (P = .14).

The combined-treatment group had a survival advantage of 2.5 months in patients with a single metastasis but not in patients with multiple lesions.

A Radiation Therapy Oncology Group (RTOG) study (RTOG-9508) randomly assigned 333 patients with one to three metastases with a maximum diameter of 4 cm to WBRT (37.5 Gy over 3 weeks) with or without a stereotactic boost.[13] Patients with active systemic disease requiring therapy were excluded. The primary end point was OS with predefined hypotheses in both the full study population and the 186 patients with a solitary metastasis (and no statistical adjustment of P values for the two separate hypotheses).[13][Levels of evidence B1 for the full study population and A1 for patients with solitary metastases]

Local control was better in the full population with combined therapy.

A Radiation Therapy Oncology Group (RTOG) study (RTOG-9508) randomly assigned 333 patients with one to three metastases with a maximum diameter of 4 cm to WBRT (37.5 Gy over 3 weeks) with or without a stereotactic boost.[13] Patients with active systemic disease requiring therapy were excluded. The primary end point was OS with predefined hypotheses in both the full study population and the 186 patients with a solitary metastasis (and no statistical adjustment of P values for the two separate hypotheses).[13][Levels of evidence B1 for the full study population and A1 for patients with solitary metastases]

At the 6-month follow-up, Karnofsky Performance status (considered a soft end point because of its imprecision and subjectivity) was better in the combined-therapy group, but there was no difference in mental status between the treatment groups. Acute and late toxicities were similar in both treatment arms. Quality of life was not assessed.

A phase III randomized trial compared adjuvant WBRT with observation after surgery or radiosurgery for a limited number of brain metastases in patients with stable solid tumors.[14][Level of evidence A3]

A phase III randomized trial compared adjuvant WBRT with observation after surgery or radiosurgery for a limited number of brain metastases in patients with stable solid tumors.[14][Level of evidence A3]

Health-related quality of life was improved in the observation-only arm, compared with WBRT.

A phase III randomized trial compared adjuvant WBRT with observation after surgery or radiosurgery for a limited number of brain metastases in patients with stable solid tumors.[14][Level of evidence A3]

Patients in the observation arm had better mean scores in physical, role, and cognitive functioning at 9 months.

A phase III randomized trial compared adjuvant WBRT with observation after surgery or radiosurgery for a limited number of brain metastases in patients with stable solid tumors.[14][Level of evidence A3]

In an exploratory analysis, statistically significant worse scores for bladder control, communication deficit, drowsiness, hair loss, motor dysfunction, leg weakness, appetite loss, constipation, nausea/vomiting, pain, and social functioning were observed in patients who underwent WBRT, compared with those who underwent observation only.

A meta-analysis of two trials with a total of 358 participants found no statistically significant difference in OS between the WBRT plus stereotactic radiosurgery group and the WBRT-alone group (HR, 0.82; 95% CI, 0.65–1.02).[15][Level of evidence B1]

A meta-analysis of two trials with a total of 358 participants found no statistically significant difference in OS between the WBRT plus stereotactic radiosurgery group and the WBRT-alone group (HR, 0.82; 95% CI, 0.65–1.02).[15][Level of evidence B1]

Patients in the WBRT plus stereotactic radiosurgery group had decreased local failure, compared with patients who received WBRT alone (HR, 0.27; 95% CI, 0.14–0.52).

A meta-analysis of two trials with a total of 358 participants found no statistically significant difference in OS between the WBRT plus stereotactic radiosurgery group and the WBRT-alone group (HR, 0.82; 95% CI, 0.65–1.02).[15][Level of evidence B1]

Unchanged or improved Karnofsky Performance status at 6 months was seen in 43% of patients in the combined-therapy group versus 28% in the WBRT-alone group (P = .03).

Studies consistently show that the addition of WBRT to focal therapy decreases the risk of progression and new metastases in the brain.

The addition of WBRT does not improve OS.

The decrease in risk of intracranial disease progression does not translate into improved functional or neurological status, nor does it appear to decrease the risk of death from neurological deterioration.

About one-half or more of the patients who receive focal therapy alone ultimately require salvage therapy, such as WBRT or radiosurgery, compared with about one-quarter of the patients who are given up-front WBRT.

The impact of better local control associated with WBRT on quality of life has not been reported and remains an open question.