Adjuvant Whole Brain Radiotherapy Research Articles

The role of surgical resection in the management of brain metastasis: a 17-year longitudinal study

Advancements over the past generation have yielded several new treatment options for the management of brain metastases. However, surgical resection (SR) still remains the mainstay of treatment and is performed especially if decompression is required. The goal of this study was to evaluate the role of surgical resection for patients with brain metastases and to find the best indications for SR. SR as an initial treatment was performed in 157 patients. Among the 157 patients, 109 (69.4 %) and 17 (10.8 %) underwent adjuvant whole-brain radiotherapy and radiosurgery, respectively. Thirty-one (19.7 %) patients did not undergo adjuvant treatment. Overall survival, tumour recurrence, and clinical outcomes were evaluated. The clinical situation was classified based on the recursive partitioning analysis (RPA) class and Karnofsky performance scale (KPS). The overall median survival was 19.3 months. Median survival according to the extent of surgical resection was 20.4 months after gross total resection (GTR) and 15.1 months after subtotal resection (STR) (P = 0.016). The patients with stable primary extracranial cancer survived longer than patients with synchronous detection of extracranial cancer (P = 0.032). The RPA I class patients showed longer survival than the RPA II class patients (P = 0.047). This difference was more prominent in the GTR group than in the STR group (GTR, P = 0.022; STR, P = 0.075). The KPS score of the GTR group changed from 82.3 to 87.0 and that of the STR group changed from 79.2 to 77.1 (P = 0.001). Adjuvant treatment did not lead to a significant improvement in the survival and clinical outcome. Surgical resection may accomplish satisfactory outcomes with technical advancement. The best indications for SR for brain metastasis are RPA I class, stable extracranial cancer, and a planned GTR of the tumour. Even with the advancements in adjuvant therapy, surgical resection plays a major role in the management of brain metastasis.

A European Organisation for Research and Treatment of Cancer Phase III Trial of Adjuvant Whole-Brain Radiotherapy Versus Observation in Patients With One to Three Brain Metastases From Solid Tumors After Surgical Resection or Radiosurgery: Quality-of-Life Results

This phase III trial compared adjuvant whole-brain radiotherapy (WBRT) with observation after either surgery or radiosurgery of a limited number of brain metastases in patients with stable solid tumors. Here, we report the health-related quality-of-life (HRQOL) results. HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, at 8 weeks, and then every 3 months for 3 years with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL scales were considered: global health status; physical, cognitive, role, and emotional functioning; and fatigue. Statistical significance required P ≤ .05, and clinical relevance required a ≥ 10-point difference. Compliance was 88.3% at baseline and dropped to 45.0% at 1 year; thus, only the first year was analyzed. Overall, patients in the observation only arm reported better HRQOL scores than did patients who received WBRT. The differences were statistically significant and clinically relevant mostly during the early follow-up period (for global health status at 9 months, physical functioning at 8 weeks, cognitive functioning at 12 months, and fatigue at 8 weeks). Exploratory analysis of all other HRQOL scales suggested worse scores for the WBRT group, but none was clinically relevant. This study shows that adjuvant WBRT after surgery or radiosurgery of a limited number of brain metastases from solid tumors may negatively impact some aspects of HRQOL, even if these effects are transitory. Consequently, observation with close monitoring with magnetic resonance imaging (as done in the EORTC trial) is not detrimental for HRQOL.

The Role of Radiosurgery to the Tumor Bed After Resection of Brain Metastases

Optimal postoperative management paradigm for brain metastases remains controversial. To conduct a systematic review of the literature to understand the role of postoperative stereotactic radiosurgery after resection of brain metastases. We performed a MEDLINE search of the literature to identify series of patients with brain metastases treated with stereotactic radiosurgery after surgical resection. Outcomes including overall survival, local control, distant intracranial failure, and salvage therapy use were recorded. Patient, tumor, and treatment factors were correlated with outcomes through the use of the Pearson correlation and 2-way Student t test as appropriate. Fourteen studies involving 629 patients were included. Median survival for all studies was 14 months. Local control was correlated with the median volume treated with radiosurgery (r = -0.766, P < .05) and with the rate of gross total resection (r = .728, P < .03). Mean crude local control was 83%; 1-year local control was 85%. Distant intracranial failure occurred in 49% of cases, and salvage whole-brain radiation therapy was required in 29% of cases. Use of a radiosurgical margin did not lead to increased local control or overall survival. Our systematic review supports the use of radiosurgery as a safe and effective strategy for adjuvant treatment of brain metastases, particularly when gross total resection has been achieved. With all limitations of comparisons between studies, no increase in local recurrence or decrease in overall survival compared with rates with adjuvant whole-brain radiation therapy was found.

Current Dosing Paradigm for Stereotactic Radiosurgery Alone After Surgical Resection of Brain Metastases Needs to Be Optimized for Improved Local Control

To describe the use of radiosurgery (RS) alone to the resection cavity after resection of brain metastases as an alternative to adjuvant whole-brain radiotherapy (WBRT). Sixty-two patients with 64 cavities were treated with linear accelerator-based RS alone to the resection cavity after surgical removal of brain metastases between March 2007 and August 2010. Fifty-two patients (81%) had a gross total resection. Median cavity volume was 8.5 cm(3). Forty-four patients (71%) had a single metastasis. Median marginal and maximum doses were 18 Gy and 20.4 Gy, respectively. Sixty-one cavities (95%) had gross tumor volume to planning target volume expansion of ≥1 mm. Six-month and 1-year actuarial local recurrence rates were 14% and 22%, respectively, with a median follow-up period of 9.7 months. Six-month and 1-year actuarial distant brain recurrence, total intracranial recurrence, and freedom from WBRT rates were 31% and 51%, 41% and 63%, and 91% and 74%, respectively. The symptomatic cavity radiation necrosis rate was 8%, with 2 patients (3%) undergoing surgery. Of the 11 local failures, 8 were in-field, 1 was marginal, and 2 were both (defined as in-field if ≥90% of recurrence within the prescription isodose and marginal if ≥90% outside of the prescription isodose). The high rate of in-field cavity failure suggests that geographic misses with highly conformal RS are not a major contributor to local recurrence. The current dosing regimen derived from Radiation Therapy Oncology Group protocol 90-05 should be optimized in this patient population before any direct comparison with WBRT.

Current Dosing Paradigm For Stereotactic Radiosurgery Alone Following Surgical Resection of Brain Metastases Needs To Be Optimized For Improved Local Control

Current Dosing Paradigm For Stereotactic Radiosurgery Alone Following Surgical Resection of Brain Metastases Needs To Be Optimized For Improved Local Control

Adjuvant Whole-Brain Radiotherapy Versus Observation after Radiosurgery or Surgical Resection of One to Three Cerebral Metastases: Results of the EORTC 22952-26001 Study

Adjuvant Whole-Brain Radiotherapy Versus Observation after Radiosurgery or Surgical Resection of One to Three Cerebral Metastases: Results of the EORTC 22952-26001 Study

Surgical management of melanoma brain metastases in patients treated with immunotherapy

Despite the increasing use of immunotherapy in the treatment of metastatic melanoma, the effects of this therapy on the management of patients with associated brain metastases are not completely defined. The authors undertook this study to determine the effectiveness of resection and the effects of immunotherapy on brain metastasis management. The authors analyzed data pertaining to consecutive patients with metastatic melanoma treated with immunotherapy within 3 months of discovery of brain metastases that were surgically resected. Forty-one patients (median age 44.4 years, range 19.2-63.1 years) underwent resection of 53 brain metastases (median number of metastases 1, range 1-4). The median metastasis volume was 2.5 cm(3). Fifteen patients underwent whole-brain radiation therapy (WBRT) and 26 patients did not. Duration of survival from brain metastasis diagnosis was not significantly different between patients who received WBRT (mean 24.9 months) and those who did not (mean 23.3 months) (p > 0.05). Local and distant brain recurrence rates were not statistically different between the WBRT (7.1% and 28.6%, respectively) and non-WBRT (7.7% and 41.0%) groups for the duration of follow-up (p > 0.05). An objective systemic response to immunotherapy was associated with increased duration of survival (p < 0.05). Resection of melanoma brain metastases in patients treated with immunotherapy provides excellent local control with low morbidity. An objective response to systemic immunotherapy is associated with a prolonged survival in patients who have undergone resection of melanoma brain metastases. Moreover, adjuvant WBRT in melanoma immunotherapy patients with limited metastatic disease to the brain does not appear to provide a significant survival benefit.

What is the randomised evidence for surgery and stereotactic radiosurgery for patients with solitary (or few) brain metastases?

Patients with solitary (or few) brain metastases are often treated with surgery (S) or stereotactic radiosurgery (SRS) with or without adjuvant whole brain radiotherapy (WBRT). This review examines the randomised evidence supporting this aggressive approach. A search of MEDLINE, EMBASE and Cochrane databases for published papers and Abstracts on relevant randomised trials was undertaken. Fourteen randomised trials were identified, 11 final reports and 3 Abstracts, investigating various combinations of S, SRS and WBRT. Most of these trials had significant limitations and the results therefore need to be viewed with caution. Surgery and SRS improve local control, maintenance of performance status and survival for favourable prognosis patients with solitary brain metastases relative to WBRT alone, although the absolute survival benefit for the majority is modest. Limited data suggest similar outcomes from S and SRS, but few patients are truly suitable for both options. For multiple (2-4) brain metastases, SRS improves local control and functional outcome but not survival; there is no randomised evidence for S. Adjuvant WBRT also improves intracranial control but not survival; however, the neurocognitive risk : benefit ratio of WBRT remains controversial. Quality of life data are currently limited.

Tumor Bed Radiosurgery following Resection of Brain Metastases: A Review

There is a growing interest in adjuvant radiosurgery following resection of hematogenous brain metastases. We have identified 12 series reporting on a total of 480 patients treated to a tumor bed following microsurgery. These cases fall into 3 paradigms: adjuvant radiosurgery as an alternative to whole-brain radiotherapy (WBRT), radiosurgery as an intensification of adjuvant WBRT and adjuvant radiosurgery for patients having failed prior WBRT. For these paradigms the reported crude local control rates are 79%, 92% and 95%, respectively. The procedure appears well tolerate with approximately a 5% risk of late radiation necrosis. Prospective data is lagging behind clinical practice and plans for prospective trials are discussed.

Adjuvant Whole-Brain Radiotherapy Versus Observation After Radiosurgery or Surgical Resection of One to Three Cerebral Metastases: Results of the EORTC 22952-26001 Study

This European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after surgery or radiosurgery of brain metastases. Patients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2. Of 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm. After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.

Quality-of-life results of an EORTC phase III randomized trial of adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases of solid tumors.

9036 Background: This study aimed to evaluate the effects of adjuvant whole brain radiotherapy (WBR) compared to no further radiotherapy after local treatment of a limited number of brain metastases in patients with stable solid tumor. We present the Health Related Quality of Life (HRQOL) results. Methods: HRQOL (EORTC QOL-C30 and BN-20) was a secondary endpoint in the trial. Out of 359, 317 patients (88.3% compliance) had baseline HRQOL assessments. Compliance was a challenge in this population: at month 6 some 51% of patients completed a HRQOL measure and at year one 45.1%. Therefore the analysis focuses on only the first year post baseline. The primary HRQOL endpoint was global QoL; secondary HRQOL endpoints were Cognitive, Physical, Emotional, Role Functioning and Fatigue. Sensitivity analyses were planned and undertaken for all scales. Statistical significance required p≤0.05 and clinical relevance ≥10 pt difference. Results: Over the year studied, there were no significant differences in the primary endpoint, global HRQOL (p<0.12). Patients who underwent WBR had a lower physical functioning score (p = 0.0325) and a deteriorated cognitive function (p = 0.006). However, the difference in physical function was clinically relevant only at week 8 and that in cognitive function only at year one. No differences between the treatments were found for role (p>0.1) or emotional functioning (p>0.1) or fatigue (p = 0.077). Exploratory analysis of several other HRQOL scales suggested worse scores for the WBR group, but these differences were not clinically relevant (<10 pt) and were not sustained in time for most other scales. Explorations also suggested that the detriment was generally greater in patients who had WBRT after radio surgery than after surgical removal of the brain metastases. Conclusions: In summary, patients who underwent WBR suffered from worse HRQOL levels, but very few differences were observed or reached the level of clinical or statistical significance. No significant financial relationships to disclose.

Adjuvant whole-brain radiation therapy after surgical resection of single brain metastases

Adjuvant whole-brain radiation therapy (WBRT) after resection of single brain metastases remains controversial. Despite a phase III trial to the contrary, clinicians often withhold WBRT after resection of single brain metastases based on the argument that available evidence does not inform regarding treatment of all patients, such as those with radioresistant tumors. However, there is limited information about whether subpopulations benefit equally from WBRT after resection. Therefore, we undertook a retrospective study to determine the clinical, radiographic, and histologic features that influenced the effectiveness of adjuvant WBRT. We reviewed 358 patients with newly diagnosed, single brain metastases, who underwent resection, of which 142 (40%) received adjuvant WBRT and 216 (60%) did not. Median follow-up was 60.1 months. There were multiple tumor histologies, including 197 (55%) "radiosensitive" and 161 (45%) "radioresistant" tumors. Compared with observation, WBRT significantly reduced recurrence both locally (HR = 0.58; 95% CI 0.35-0.98, P = .04) and at distant brain sites (HR = 0.43, 95% CI 0.30-0.61, P < .001). Multivariate analyses demonstrated that withholding WBRT was an independent predictor of local and distant recurrence. For local recurrence, tumors with a maximum diameter of ≥3 cm that did not receive adjuvant WBRT had an increased risk of recurring locally (HR = 3.14, 95% CI 1.02-9.69, P = .05). For distant recurrence, patients whose primary disease was progressing and who did not receive WBRT had an increased risk of distant recurrence (HR = 2.16, 95% CI 1.01-4.66, P = .05). There was no effect of WBRT based on tumor type. Adjuvant WBRT significantly reduces local and distant recurrences in subsets of patients, particularly those with metastases >3 cm or with active systemic disease.

Whole-brain radiation therapy in melanoma: an open question

We congratulate Chang and colleagues for their trial assessing the neurocognitive effects of adjuvant whole-brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) for brain metastases.1 However, we must disagree with their recommendations regarding melanoma patients. They suggest that “for the so-called radioresistant brain metastases from melanoma, renal-cell carcinoma and sarcoma, it might be even more justified to omit WBRT for one to three brain metastases, as it is thought that WBRT is less effective in this setting.” Their data do not support this recommendation.

Stereotactic radiosurgery boost to the resection bed for oligometastatic brain disease: challenging the tradition of adjuvant whole-brain radiotherapy

Whole-brain radiation therapy (WBRT) has been the traditional approach to minimize the risk of intracranial recurrence following resection of brain metastases, despite its potential for late neurotoxicity. In 2007, the authors demonstrated an equivalent local recurrence rate to WBRT by using stereotactic radiosurgery (SRS) to the operative bed, sparing 72% of their patients WBRT. They now update their initial experience with additional patients and more mature follow-up. The authors performed a retrospective review of all cases involving patients with limited intracranial metastatic disease (< or = 4 lesions) treated at their institution with SRS to the operative bed following resection. No patient had prior cranial radiation and WBRT was used only for salvage. From November 2000 to June 2009, 52 patients with a median age of 61 years met inclusion criteria. A single metastasis was resected in each patient. Thirty-four of the patients each had 1 lesion, 13 had 2 lesions, 3 had 3 lesions, and 2 had 4 lesions. A median dose of 1500 cGy (range 800-1800 cGy) was delivered to the resection bed targeting a median volume of 3.85 cm(3) (range 0.08-22 cm(3)). With a median follow-up of 13 months, the median survival was 15.0 months. Four patients (7.7%) had a local recurrence within the surgical site. Twenty-three patients (44%) ultimately developed distant brain recurrences at a median of 16 months postresection, and 16 (30.7%) received salvage WBRT (8 for diffuse disease [> 3 lesions], 4 for local recurrence, and 4 for diffuse progression following salvage SRS). The median time to WBRT administration postresection was 8.7 months (range 2-43 months). On univariate analysis, patient factors of a solitary tumor (19.0 vs 12 months, p = 0.02), a recursive partitioning analysis (RPA) Class I (21 vs 13 months, p = 0.03), and no extracranial disease on presentation (22 vs 13 months, p = 0.01) were significantly associated with longer survival. Cox multivariate analysis showed a significant association with longer survival for the patient factors of no extracranial disease on presentation (p = 0.01) and solitary intracranial metastasis (p = 0.02). Among patients with no extracranial disease, a solitary intracranial metastasis conferred significant additional survival advantage (43 vs 10.5 months, p = 0.05, log-rank test). No factor (age, RPA class, tumor size or histological type, disease burden, extent of resection, or SRS dose or volume) was related to the need for salvage WBRT. Adjuvant SRS to the metastatic intracranial operative bed results in a local recurrence rate equivalent to adjuvant WBRT. In combination with SRS for unresected lesions and routine imaging surveillance, this approach achieves robust overall survival (median 15 months) while sparing 70% of the patients WBRT and its potential acute and chronic toxicity.

Whole-brain radiotherapy and tumor bed radiosurgery following resection of solitary brain metastases

A standard approach to solitary brain metastases is resection followed by whole-brain radiation therapy (WBRT). Despite WBRT, the tumor bed remains a common site of failure. We reviewed outcomes following adjuvant WBRT with tumor bed radiosurgery (SRS). We retrospectively identified patients having undergone neurosurgical resection of a single brain metastasis followed by adjuvant WBRT and tumor bed SRS. SRS dose selection was independent of target volume (10 Gy peripheral dose). Outcomes were calculated actuarially. Patients were censured for local control at the time of last imaging. From 2005 to 2008, 27 patients were treated with WBRT and tumor bed SRS. Median age was 58.7 years, median KPS 80%. The primary malignancy was non-small cell lung cancer in 70%. Median follow-up was 9.7 months. Following the combination of surgery, WBRT and SRS the median overall survival was 17.6 months. Actuarial 2-year local control was 94%. The SRS boost was well tolerated with one patient (4%) requiring reoperation for symptomatic radiation necrosis 16 months post treatment. Radiosurgery can be safely added to WBRT as an adjuvant treatment following resection of a single brain metastasis. In our retrospective series, this combination treatment produced a high rate of local control.

Treatment options for central nervous system lymphomas in immunocompetent patients

Despite recent advances in diagnosis and treatment, the prognosis of primary CNS lymphoma (PCNSL) and CNS relapse of systemic non-Hodgkin lymphoma remains poor, and the optimal treatment is yet to be defined. This review presents an overview of the current status of CNS lymphoma treatment. Treatment options include radiotherapy alone, intravenous conventional chemotherapy alone, intrathecal chemotherapy, high-dose chemotherapy with autologous stem cell transplantation, combined modality treatment (i.e., chemotherapy plus radiotherapy), immunotherapy, radioimmunotherapy and ocular radiation and/or chemotherapy for intraocular lymphoma. High-dose methotrexate remains an essential part of most first-line treatments for PCNSL and CNS relapse of systemic non-Hodgkin lymphoma. Treatment standardization is hampered by the rarity of the disease and the difficulty of conducting trials with a higher number of patients. However, a recently closed Phase III/IV trial will most likely define the role of adjuvant whole-brain radiation treatment in PCNSL. Future directions in the management of PCNSL and CNS relapse of systemic lymphoma may include treatment stratification according to patient age and clinical and biological prognostic factors.

Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of 1–3 cerebral metastases: Results of the EORTC 22952–26001 study

2008 Background: The EORTC Radiotherapy and Brain Tumor Groups conducted a phase III trial to define the role of adjuvant whole brain irradiation (WBRT) after local treatment (surgery or radiosurgery) for brain metastases. It was hypothetized that WBRT would increase the duration of functional independence by reducing the number of intracranial relapses. Methods: Pts eligible for radiosurgery (RS) had 1–3 metastases of solid tumors (SCLC excluded) ≤ 3.0 cm in diameter (≤ 2.5 cm for 2–3 lesions). In case of surgery (S), a complete resection was mandatory. Only pts with no or stable systemic disease or with asymptomatic synchronous primary tumors, and with WHO PS 0–2 were allowed. Pts were randomized for adjuvant WBRT or observation (OBS). Primary endpoint was survival with functional independence measured by the time to WHO PS deterioration to &gt; 3. Analysis is by intent-to-treat (Logrank, two-sided α = 0.05). Results: From 1996–2007, 359 pts were recruited. 160 surgical pts had resection of one (96%) or two (4%) metastases, and 185 (of 199 scheduled pts) had RS (marginal dose 20Gy, target dose 25Gy) of one (67%), two (23%), or three (10%) lesions. Adjuvant whole brain irradiation (30Gy/10 fractions) was given to 166/180 pts. (92%) randomized for WBRT and to 4/179 pts (2%) in the OBS arm. Median time to WHO PS &gt; 3 was 9.8 months (95% CI 8.0 - 11.7) in the OBS arm and 9.8 months (95% CI 7.8 - 12.6) in the WBRT arm (p &gt; 0.5). It was only significantly influenced by initial WHO PS and initial systemic disease status (p &lt; 0.01). Overall survival was 10.9 months (95% CI 9.2 - 14.6) in both arms (p &gt; 0.5). Cumulative incidence of intracranial progression at 6 and 24 months was 39.7% (95% CI 32.5 - 46.8) and 54.0% (95% CI 46.7 - 61.3) of the OBS pts, but only 15.2% (95% CI 9.9 - 20.5) and 31.4% (95% CI 24.5 - 38.2) of the WBRT pts (p &lt; 0.0001). Intracranial progression was a cause of the death in 77/179 pts (43%) of the OBS group and in only 45/180 pts (25%) of the WBRT group. Conclusions: After radiosurgery or surgery of 1–3 brain metastases, adjuvant WBRT reduces the frequency of intracranial relapses and neurologic deaths but fails to prolong the time period of functional independence and overall survial time. Updated results will be presented at the Meeting. No significant financial relationships to disclose.

Modern treatment of cerebral metastases: Integrated Medical LearningSM at CNS 2007

Cerebral metastases are a common problem and pose complex treatment decisions, with reference to local control of treated lesions, prevention of new brain metastases, and toxicity of available treatments. At the 2007 Congress of Neurological Surgeons (CNS) Annual Meeting, a novel active learning process, called Integrated Medical Learning(SM), was used to better understand contemporary practice patterns and to monitor the success of education about these critical treatment decisions. CNS members received an electronically distributed premeeting survey and educational materials about single and multiple cerebral metastasis treatment; practice patterns were elicited. At the Annual Meeting, 496 surgeons were polled using handheld devices before and after surgical and radiation oncology expert presentations. Surgeons who had answered premeeting surveys received a second, postmeeting questionnaire. In the premeeting questionnaire (N = 214), higher current volume of practice, Tumor Section membership, and academic practice predicted more correct answers (P < 0.05 for all). Fifty five percent favored routine whole brain radiotherapy (WBRT) after metastasis resection. Thirty four percent "most often" used radiosurgery to the resection bed; these respondents cited "cognitive changes" in justifying WBRT omission. At the meeting, expert presentations were followed by audience shifts toward adjuvant WBRT after resection (P = 0.01) or radiosurgery (P < 0.001)-topics for which class I evidence was discussed. There was no shift in preference for surgery or radiosurgery (P = 0.24) or multiple metastasis treatment (P = 0.8)-topics for which clear class I evidence was not presented. Postmeeting questionnaires showed retained knowledge among meeting attendees. Using IML, we were able to study baseline knowledge and practice patterns for an important neuro-oncological treatment decision. Evidence suggested expert presentations were effective in changing audience opinion when relevant class I evidence was presented, and that knowledge was retained postmeeting.

Surgical resection and permanent iodine-125 brachytherapy for brain metastases

To evaluate the efficacy and toxicity of surgical resection and permanent iodine-125 brachytherapy without adjuvant whole brain radiation therapy (WBRT) for brain metastases. Forty patients were treated with permanent iodine-125 brachytherapy at the time of resection of brain metastases from 1997 to 2003. Actuarial freedom from progression (FFP) and survival were measured from the date of surgery and estimated using the Kaplan-Meier method, with censoring at last imaging for FFP endpoints. The median survival was 11.3 months overall, 12.0 months in 19 patients with newly diagnosed brain metastases and 7.3 months in 21 patients with recurrent brain metastases. Twenty-two patients (55%) remained free of progression of brain metastases, three failed at the resection cavity (including one with leptomeningeal dissemination), two failed with leptomeningeal spread only, and 13 failed elsewhere in the brain including two who also had leptomeningeal disease. The 1-year resection cavity FFP probabilities were 92%, 86% and 88%; and brain FFP probabilities were 29%, 43% and 37% for the newly diagnosed, recurrent and all patients, respectively. Symptomatic necrosis developed 7.4-40.0 months (median, 19.5 months) after brachytherapy in 9 patients (23%), confirmed by resection in 6 patients. Excellent local control was achieved using permanent iodine-125 brachytherapy for brain metastasis resection cavities, although there is a high risk of radiation necrosis over time. These data support consideration of permanent brachytherapy without adjuvant WBRT as a treatment option in patients with symptomatic or large newly diagnosed or recurrent brain metastases.

Commentary

The benefit of whole-brain radiation therapy (WBRT) following stereotactic radiation surgery (SRS) for brain metastases is controversial. We conducted a systematic analysis of published literature to explore the outcome of brain metastases treated with SRS and WBRT versus SRS alone using PubMed and MEDLINE. Outcomes including survival, control, salvage therapy, and other quality of life measures were reported. Three randomized controlled trials involving 389 patients with 1 to 4 brain metastases were selected. In 2 of these trials (n = 190), the mean 1-year survival was 33.2% for SRS + WBRT and 38.7% for SRS alone (P = .5233); 1-year local control was 89% for SRS + WBRT and 71% for SRS alone (P < .001). Mean crude distant recurrence rate for SRS + WBRT was 36.6% and 54% for SRS alone (P < .001). Patients without WBRT were over 3 times more likely to require salvage therapy (P < .001). The addition of WBRT was associated with a decreased health-related quality of life assessment, mini mental status exam, and Hopkins Verbal Learning Test (P < .05). Five retrospective studies (n = 1122) were also included in a separate analysis and yielded findings that supported results from the randomized trials. Our systematic analysis demonstrates that adjuvant WBRT following SRS for the treatment of oligometastases in the brain is more effective at controlling local and distant recurrence than SRS alone, but there is no apparent benefit for survival or symptomology. The proven cognitive decline and neurotoxicity present with WBRT should be weighed against the benefit of local control. Prognosis of brain metastasis is poor regardless of current treatment and further exploration for alternative adjuvant treatment for SRS is warranted.