Purpose To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and Materials Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. Results The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Conclusions Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).

https://www.practicalradonc.org/article/S1879-8500(11)00380-8/pdf

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline

Purpose To evaluate local control after surgical resection and postoperative stereotactic radiosurgery (SRS) for brain metastases. Methods and Materials A total of 49 patients (50 lesions) were enrolled and available for analysis. Eligibility criteria included histologically confirmed malignancy with 1 or 2 intraparenchymal brain metastases, age ≥18 years, and Karnofsky performance status (KPS) ≥70. A Cox proportional hazard regression model was used to test for significant associations between clinical factors and overall survival (OS). Competing risks regression models, as well as cumulative incidence functions, were fit using the method of Fine and Gray to assess the association between clinical factors and both local failure (LF; recurrence within surgical cavity or SRS target), and regional failure (RF; intracranial metastasis outside of treated volume). Results The median follow-up was 12.0 months (range, 1.0-94.1 months). After surgical resection, 39 patients with 40 lesions were treated a median of 31 days (range, 7-56 days) later with SRS to the surgical bed to a median dose of 1800 cGy (range, 1500-2200 cGy). Of the 50 lesions, 15 (30%) demonstrated LF after surgery. The cumulative LF and RF rates were 22% and 44% at 12 months. Patients who went on to receive SRS had a significantly lower incidence of LF ( P =.008). Other factors associated with improved local control include non-small cell lung cancer histology ( P =.048), tumor diameter P =.010), and deep parenchymal tumors ( P =.036). Large tumors (≥3 cm) with superficial dural/pial involvement showed the highest risk for LF (53.3% at 12 months). Large superficial lesions treated with SRS had a 54.5% LF. Infratentorial lesions were associated with a higher risk of developing RF compared to supratentorial lesions ( P Conclusions Postoperative SRS is associated with high rates of local control, especially for deep brain metastases

A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases.

Object As a strategy to delay or avoid whole-brain radiotherapy (WBRT) after resection of a brain metastasis, the authors used high-resolution MR imaging and cavity-directed radiosurgery for the detection and treatment of further metastases Methods Between April 2001 and October 2009, 112 resection cavities in 106 patients with no prior WBRT were treated using radiosurgery directed to the tumor cavity and for any synchronous brain metastases detected on high-resolution MR imaging at the time of radiosurgical planning A median dose of 17 Gy to the 50% isodose line was prescribed to the gross tumor volume, defined as the rim of enhancement around the resection cavity Patients were followed up via serial imaging, and new brain metastases were generally treated using additional radiosurgery, with salvage WBRT typically reserved for local treatment failure at a resection cavity, numerous failures, or failures occurring at short time intervals Local and distant treatment failures were determined based on im

Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis.

Purpose Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. Methods and Materials Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. Results Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc ( P =.01), >3.4 cm ( P =.014), with a trend in surface lesions ( P =.066) and eloquent areas ( P =.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. Conclusions NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong majority of patients were able to avoid WBRT. NaSRS merits consideration in a multi-institution trial.

A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence

Object This study evaluated the efficacy of postoperative Gamma Knife surgery (GKS) to the tumor cavity following gross-total resection of a brain metastasis. Methods A retrospective review was conducted of 700 patients who were treated for brain metastases using GKS. Forty-seven patients with pathologically confirmed metastatic disease underwent GKS to the postoperative resection cavity following gross-total resection of the tumor. Patients who underwent subtotal resection or who had visible tumor in the resection cavity on the postresection neuroimaging study (either CT or MR imaging with and without contrast administration) were excluded. Radiographic and clinical follow-up was assessed using clinic visits and MR imaging. The radiographic end point was defined as tumor growth control (no tumor growth regarding the resection cavity, and stable or decreasing tumor size for the other metastatic targets). Clinical end points were defined as functional status (assessed prospectively using the Karnofsky Perf...

Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases

OBJECTVE: Adjuvant irradiation after resection of brain metastases reduces the risk of local recurrence. Whole-brain radiation therapy can be associated with significant neurotoxicity in long-term survivors of brain metastases. This retrospective study evaluates the role of tumor bed stereotactic radiosurgery as an alternative method of irradiation after initial resection of brain metastases to prevent local recurrence. METHODS: Forty patients underwent tumor bed radiosurgery after resection of brain metastases at two separate academic medical centers. The median age was 59.5 years. Twenty patients (67.5%) had single metastases. Resection was complete in 80% and partial in 20% of the patients. At the time of radiosurgery, systemic disease was active in 57.5%, inactive in 32.5%, and in remission in 10% of the patients. The median Karnofsky Performance Scale score was 80% (range, 60-100%). Radiosurgery was performed a median of 4 weeks after tumor resection. The median cavity radiosurgery volume was 9.1 ml (range, 0.6-39.9 ml). The median margin and maximum radiation dose were 16 and 32 Gy, respectively. RESULTS: Local control at the resection site was achieved in 73% of patients at a median follow-up period of 13 months. No variable significantly affected local control. New remote brain metastases occurred in 54% of the patients. Symptomatic radiation effect was seen in 5.4% of the patients. The median survival was 13 months after radiosurgery (range, 2-56 mo). CONCLUSION: Tumor bed radiosurgery provides effective local control of the tumor after resection in most patients. These preliminary data support radiosurgery after resection rather than traditional radiation therapy.

Tumor bed radiosurgery after resection of cerebral metastases.

BACKGROUND

Metastases to the brain from ovarian and endometrial carcinoma are uncommon and to the authors' knowledge consensus regarding optimal management is lacking. Stereotactic radiosurgery (SRS) has proven useful for the treatment of many benign and malignant brain tumors. In the current study, the authors evaluated outcomes after SRS in patients with ovarian and endometrial carcinoma.



METHODS

Twenty-seven patients with brain metastases underwent gamma–knife SRS. Six patients had endometrial carcinoma, whereas 21 patients had ovarian carcinoma. Eighteen patients also received whole–brain radiotherapy. A total of 68 tumors were treated with gamma–knife SRS.



RESULTS

At the time of last follow–up, 1 patient was still alive and 26 had died. The median survival was 7 months after the initial diagnosis of brain metastasis and 5 months after SRS. The 1-year survival rate after radiosurgery was 15% and that from the diagnosis of brain metastases was 22%. On final imaging, all tumors were controlled without further growth. Two patients (7.4%) developed new or progressive neurologic deficits after SRS.



CONCLUSIONS

SRS is an acceptable choice for the treatment of brain metastases resulting from ovarian and endometrial carcinoma, and provides local tumor control with limited morbidity. Careful patient selection is warranted in the setting of patients with uncontrolled systemic disease in whom a limited survival benefit is expected. Cancer 2008. © 2008 American Cancer Society.

Management of brain metastases from ovarian and endometrial carcinoma with stereotactic radiosurgery.

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Tumor bed radiosurgery after resection of cerebral metastases.

Management of brain metastases from ovarian and endometrial carcinoma with stereotactic radiosurgery.