Less cognitive decline with stereotactic radiosurgery after brain metastases resection

BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.

In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.

In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.

“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.

WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.

The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.

WBRT vs. SRS

To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.

Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.

Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.

After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.

There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).

The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).

Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).

Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.

Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.

SRS vs. observation

In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.

The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.

“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.

The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.

BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.

In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.

In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.

“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.

WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.

The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.

WBRT vs. SRS

To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.

Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.

Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.

After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.

There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).

The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).

Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).

Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.

Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.

SRS vs. observation

In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.

The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.

“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.

The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.

BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.

In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.

In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.

“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.

WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.

The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.

WBRT vs. SRS

To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.

Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.

Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.

After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.

There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).

The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).

Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).

Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.

Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.

SRS vs. observation

In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.

The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.

“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.

The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.