Long-term survivors after gamma knife radiosurgery for brain metastases

BACKGROUND: Stereotactic radiosurgery, with or without whole-brain radiation therapy, has become a valued management choice for patients with brain metastases, although their median survival remains limited. In patients who receive successful extracranial cancer care, patients who have controlled intracranial disease are living longer. The authors evaluated all brain metastasis in patients who lived for > or = 4 years after radiosurgery to determine clinical and treatment patterns potentially responsible for their outcome. METHODS: Six hundred seventy-seven patients with brain metastases underwent 781 radiosurgery procedures between 1988 and 2000. Data from the entire series were reviewed; and, if patients had > or = 4 years of survival, then they were evaluated for information on brain and extracranial treatment, symptoms, imaging responses, need for further care, and management morbidity. These long-term survivors were compared with a cohort who lived for < 3 months after radiosurgery (n = 100 patients). RESULTS: Forty-four patients (6.5%) survived for > 4 years after radiosurgery (mean, 69 mos with 16 patients still alive). The mean age at radiosurgery was 53 years (maximum age, 72 yrs), and the median Karnofsky performance score (KPS) was 90. The lung (n = 15 patients), breast (n = 9 patients), kidney (n = 7 patients), and skin (melanoma; n = 6 patients) were the most frequent primary sites. Two or more organ sites outside the brain were involved in 18 patients (41%), the primary tumor plus lymph nodes were involved in 10 patients (23%), only the primary tumor was involved in 9 patients (20%), and only brain disease was involved in 7 patients (16%), indicating that extended survival was possible even in patients with multiorgan disease. Serial imaging of 133 tumors showed that 99 tumors were smaller (74%), 22 tumors were unchanged (17%), and 12 tumors were larger (9%). Four patients had a permanent neurologic deficit after brain tumor management, and six patients underwent a resection after radiosurgery. Compared with the patients who had limited survival (< 3 mos), long-term survivors had a higher initial KPS (P = 0.01), fewer brain metastases (P = 0.04), and less extracranial disease (P < 0.00005). CONCLUSIONS: Although the expected survival of patients with brain metastases may be limited, selected patients with effective intracranial and extracranial care for malignant disease can have prolonged, good-quality survival. The extent of extracranial disease at the time of radiosurgery was predictive of outcome, but this does not necessarily mean that patients cannot live for years if treatment is effective.     

Two cases of lung cancer patients with postoperative brain metastases obtaining long-term survival after gamma knife radiosurgery

We report two cases of lung cancer patients with postoperative solitary brain metastases obtaining long-term survival after gamma knife stereotactic radiosurgery. Both were seventies men and had good performance status without active extracranial disease. In one case, an asymptomatic metastatic brain tumor 1.8 cm in maximum diameter appeared one year and two months after the operation and was irradiated with gamma knife resulting in complete local control for seven years. He is alive with solitary lung metastasis in good performance status. In the other case, gamma knife was employed for a metastatic brain tumor 2.7 cm in maximum diameter that appeared nine months after the operation accompanying incomplete left hemiplegia. Six months later, the tumor was enlarged and gamma knife was repeated, but the tumor growth could not be suppressed. Following deterioration of hemiplegia and appearance of convulsion, he died of neurological disorder three years and two months after the onset of brain metastasis. Gamma knife stereotactic radiosurgery for metastatic brain tumors is less invasive and a repeatable technique, and is expected to provide a good local control and a survival benefit for appropriately selected patients.     

The role of whole-brain radiation therapy after stereotactic radiation surgery for brain metastases

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.     

Evaluation of mini-mental status examination score after gamma knife radiosurgery as the first radiation treatment for brain metastases

This study evaluated the mini-mental status examination (MMSE) scores of patients with brain metastases after gamma knife radiosurgery (GKS) without whole-brain radiation therapy (WBRT). Between January 2009 and June 2011, 119 consecutive patients with new brain metastases were treated with a single session of GKS without WBRT. MMSE scores were determined for all patients before GKS and for surviving patients every 3 months after GKS. We evaluated 76 patients (63.9 %) after GKS. The median pre-GKS MMSE score was 28 (range 3–30). The median age, number of brain metastases, and total volume of brain metastases were 65.5 years (range 40–92 years), 2 (range 1–18), and 4.17 ml (range 0.04–27.0 ml), respectively. The median marginal dose was 22.0 Gy (range 14–24 Gy). Thirty-nine patients (51.3 %) developed new distant lesions. The median MMSE follow-up time was 5.8 months (range 0.9–21.6 months). In 16 of 37 patients (43.2 %) with pre-GKS MMSE scores ≤27, the MMSE scores improved by ≥3 points, whereas 15 of all patients (19.7 %) experienced deteriorations of ≥3 points. The incidences of 3-point drops due to new distant lesions and adverse radiation effects were 2.6 and 1.3 %, respectively. The 12-month rate of 3-point drops of the MMSE score due to these 2 causes was 4.2 % (1 of 24 patients). A larger tumor volume was a better prognostic factor for an improvement. GKS has a mild effect on neurocognitive function. Mental deterioration of patients with large symptomatic metastatic tumors tended to improve after GKS.     

The efficacy of gamma knife radiosurgery for advanced gastric cancer with brain metastases

The aim of this study was to retrospectively investigate the efficacy of gamma knife radiosurgery for brain metastases from advanced gastric cancer (AGC) comparing whole brain radiotherapy (WBRT). Between January 1991 and May 2008, 56 patients with brain metastases from AGC, treated with GKR or WBRT, were reviewed to assess prognostic factors affecting survival. Most brain metastases were diagnosed based on MRI, both metachronous and synchronous brain metastases, adenocarcinoma and signet ring carcinoma were included, but excluded cases of gastric lymphoma. Fifteen patients with a median age of 54.0 years (range, 42–67 years) were treated with GKR: 11 were treated with GKR only, 2 with surgery plus GKR, 1 with repeated GKR, 1 with GKR plus WBRT, and the other 1 with WBRT plus GKR. Forty-one were treated with WBRT only. The median number of metastatic brain lesions was 3 (range, 1–15), and treatment involved 17.0 Gy (range 14–23.6 Gy), or 30 Gy with fractionated radiotherapy. The median survival after brain metastases for GKR treatment was 40.0 weeks [95% confidence interval (CI) 44.9–132.1 weeks] and WBRT was 9.0 weeks 95% CI, 8.8–21.9 weeks). The progression free survival of 15 GKR treated patients was 56.5 weeks (95% CI 33.4–79.5 weeks). The recursive partitioning analysis (RPA) (class 2 vs. class 3) and use of GKR were correlated with prolonged survival in univariate and multivariate analyses. Age, sex, pathology, leptomeningeal seeding, tumor size (≥3 cm), extracranial metastases, single metastasis, chemotherapy, and synchronous metastases were not correlated with a good prognosis in both univariate and multivariate analysis. Based on our study, the use of GKR and RPA class 2 resulted in more favorable clinical outcomes in patients with brain metastases from AGC.     

Influence of gamma knife radiosurgery on the quality of life in patients with brain metastases

Quality of life (QOL) is an important issue in the treatment of patients with brain metastases. With median survival times often less than 4 months, less invasive treatment options that maximize QOL parameters are essential. In recent years, stereotactic radiosurgery (SRS) has been commonly used as a noninvasive alternative to surgical resection for such patients. This prospective study was undertaken to evaluate QOL in patients undergoing SRS for brain metastases. Between 1999 and 2000, 20 patients with metastatic disease to the brain were evaluated and treated in our Gamma Knife unit. All patients performed the Spitzer QOL survey (10-point scale) both before stereotactic radiosurgery and at each follow-up visit. Primary sites of disease included lung (n = 10), breast (n = 5), melanoma (n = 2), thyroid (n = 1), uterine (n = 1), and kidney (n = 1). Fifteen (75%) had prior whole brain radiotherapy (median dose: 35 Gy). The median age and Karnofsky Performance Status were 58 years and 80, respectively. The median Spitzer score before SRS was 9 (range: 7-10), and the median follow-up time of the patients in this series was 7 months. The median posttreatment Spitzer score at 1 and 3 months after SRS was 9 (range: 5-10) and 8 (range: 4-10), respectively. Crude intracranial tumor control in this cohort of patients was 90%. Extracranial tumor progression was noted in 8 patients (40%), and in these patients, Spitzer scores tended to decrease in value. In those patients who had no evidence of intracranial or extracranial tumor progression, Spitzer scores remained either unchanged or improved. Gamma knife SRS is an appropriate treatment modality for maintaining QOL parameters in patients with brain metastases. Tumor progression both intracranially and extracranially influences QOL parameters. Confirmation of this finding will require further investigation.     

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.     

Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases

PURPOSE: To better evaluate tumor control and toxicity from radiosurgery for brain metastases, we analyzed these outcomes in patients who had survived at least 1 year after radiosurgery. METHODS AND MATERIALS: We evaluated the results of gamma knife stereotactic radiosurgery (SRS) for 208 brain metastases in 137 patients who were followed for a median of 18 months (range 12-122) after radiosurgery. The median patient age was 53 years (range 3-83). Ninety-nine patients had solitary metastases. Thirty-eight had multiple tumors. Sixty-nine patients underwent initial SRS with whole brain radiotherapy (WBRT), 39 had initial SRS alone, and 27 patients had failed prior WBRT. The median treatment volume was 1.9 cm(3) (range 0.05-21.2). The median marginal tumor dose was 16 Gy (range 12-25). The most common histologic types included non-small-cell lung cancer, breast cancer, melanoma, and renal cell carcinoma, which comprised 37.0%, 22.6%, 13.0%, and 9.13% of the lesions, respectively. Forty-five tumors were associated with extensive edema. RESULTS: At 1 and 5 years, the local tumor control rate was 89.6% +/- 2.1% and 62.8% +/- 6.9%, distal intracranial relapse occurred in 23% +/- 3.6% and 67.1% +/- 8.7%, and postradiosurgical sequelae developed in 2.8% +/- 1.2% and 11.4% +/- 3.5% of patients, respectively. Multivariate analysis found that local control decreased with tumor volume (p = 0.0002), SRS without WBRT (p = 0.008), and extensive edema (p = 0.024); distal intracranial recurrence correlated with younger patient age (p = 0.0018); and postradiosurgical sequelae increased with increasing tumor volume (p = 0.0085). CONCLUSION: Long-term control of brain metastases and complication rates in this selective series of patients surviving >or=1 year after radiosurgery were similar to previously reported actuarial estimates. Large metastases and metastases associated with extensive edema can be difficult to control by radiosurgery, particularly without WBRT.     

脑转移瘤伽玛刀配合全脑放疗的临床研究

目的探讨脑转移瘤伽玛刀治疗配合全脑放疗的疗效。方法自2002年3月至2006年3月收治脑转移瘤患者79例。原发灶控制稳定,脑转移患者中,44例采用伽玛刀配合全脑放疗,35例单纯给予伽玛刀治疗。伽玛刀治疗处方等剂量线采用45%～75%等剂量包绕计划靶区,边缘剂量15～20 Gy,中心30～45 Gy;全脑放疗每次分割剂量为2～3 Gy,1次/d,每周照射5次,总剂量25～30 Gy。结果伽玛刀治疗开始后3个月,复查MRI,影像学结果显示总的有效率为83.5%（66/79）。伽玛刀配合全脑放疗组的1年生存率为29.5%,2年生存率9.1%;单纯伽玛刀组患者的1年生存率为17.1%,2年生存率2.9%。随访期内未见严重放射性并发症。结论对脑转移瘤采用伽玛刀配合全脑放疗是较有效的局部治疗方式,副反应轻,均能耐受治疗。     

Multivoxel proton MRS for differentiation of radiation-induced necrosis and tumor recurrence after gamma knife radiosurgery for brain metastases

Multivoxel proton magnetic resonance spectroscopy (MRS) was used for differentiation of radiation-induced necrosis and tumor recurrence after gamma knife radiosurgery for intracranial metastases in 33 consecutive cases. All patients presented with enlargement of the treated lesion, increase of perilesional brain edema, and aggravation or appearance of neurological signs and symptoms on average 9.3 ± 4.9 months after primary treatment. Metabolic imaging defined four types of lesions: pure tumor recurrence (11 cases), partial tumor recurrence (11 cases), radiation-induced tumor necrosis (10 cases), and radiation-induced necrosis of the peritumoral brain (1 case). In 1 patient, radiation-induced tumor necrosis was diagnosed 9 months after radiosurgery; however, partial tumor recurrence was identified 6 months later. With the exception of midline shift, which was found to be more typical for radiation-induced necrosis (P < 0.01), no one clinical, radiologic, or radiosurgical parameter either at the time of primary treatment or at the time of deterioration showed a statistically significant association with the type of the lesion. Proton MRS-based diagnosis was confirmed histologically in all surgically treated patients (7 cases) and corresponded well to the clinical course in others. In conclusion, multivoxel proton MRS is an effective diagnostic modality for identification of radiation-induced necrosis and tumor recurrence that can be used for monitoring of metabolic changes in intracranial neoplasms after radiosurgical treatment. It can be also helpful for differentiation of radiation-induced necrosis of the tumor and that of the peritumoral brain, which may have important clinical and medicolegal implications.     

Long-term survival after gamma knife radiosurgery for primary and metastatic brain tumors

In this paper, we studied factors related to long-term survival after gamma knife radiosurgery (GKS) for primary and metastatic brain tumors. We examined all cases of brain metastases and malignant glioma treated with GKS between September 1994 and December 1998. All patients with survival exceeding 2 years were studied retrospectively using prospectively acquired data. A total of 22 patients, with an average age of 56, were identified, which accounts for 11% of the total patients treated during this time interval. Seventeen of 22 are still alive with a mean follow-up of 48 months. Sixteen patients had metastatic tumors, whereas 6 had a malignant glioma. Thirteen of 15 patients with metastases had a controlled primary site, and the other 2 patients did not have a primary site identified. These 2 patients were among the 3 that died during the follow-up period. Fourteen patients developed symptomatic radiation necrosis by MRI criteria with 4 confirmed by biopsy. Quality-of-life factors were assessed in 20 of 22 patients using a modified Spitzer scale, which showed a high level of functioning in all of the long-term survivors (mean score 8.65 of 10), and only 1 patient had a Karnofsky Performance Score of less than 70. We conclude that radiosurgery provides a noninvasive and effective way of controlling brain tumors, while preserving quality of life.     

Predictive factors of early distant brain failure after gamma knife radiosurgery alone in patients with brain metastases of non-small-cell lung cancer

The objective of this study was to elucidate the predictive factors for early distant brain failure in patients with brain metastases of non-small-cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKRS) without previous whole-brain radiotherapy (WBRT) or surgery. We retrospectively reviewed clinical and imaging data of 459 patients with brain metastases of NSCLC who underwent GKRS from June 2008 to December 2013. The primary end-point was early distant brain failure, defined as the detection of newly developed metastatic lesions on magnetic resonance imaging (MRI) 3 months after GKRS. Factors such as tumor pathology subtype, concurrent systemic chemotherapy, epidermal growth factor receptor (EGFR) mutation status, use of EGFR tyrosine kinase inhibitors (TKIs), systemic disease status, presence of a metastatic lesion only in delayed MRI, and volume and number of metastases were analyzed. There were no statistically significant differences with respect to pathologic subtype, concurrent systemic chemotherapy, EGFR mutation, and early distant brain failure. Patients treated with EGFR-TKIs (p?=?0.004), with a stable systemic disease status (p?=?0.028) and 3 or fewer brain lesions (p?=?0.000) experienced a significantly lower incidence of early distant brain failure. This study suggests that GKRS alone could be considered for patients treated with EGFR-TKIs who have a stable systemic disease status and 3 or fewer brain lesions. WBRT should be considered for other patients.     

A volume matched comparison of survival after radiosurgery in non-small cell lung cancer patients with one versus more than twenty brain metastases

Journal of Neuro-Oncology - Treatment of patients with a large number of brain metastases using radiosurgery remains controversial. In this study we sought to conduct a volume matched comparison to...     

Local control after fractionated stereotactic radiation therapy for brain metastases

Stereotactic radiosurgery (SRS) is frequently used in the management of brain metastases, but concerns over potential toxicity limit applications for larger lesions or those in eloquent areas. Fractionated stereotactic radiation therapy (SRT) is often substituted for SRS in these cases. We retrospectively analyzed the efficacy and toxicity outcomes of patients who received SRT at our institution. Seventy patients with brain metastases treated with SRT from 2006–2012 were analyzed. The rates of local and distant intracranial progression, overall survival, acute toxicity, and radionecrosis were determined. The SRT regimen was 25 Gy in 5 fractions among 87 % of patients. The most common tumor histologies were non-small cell lung cancer (37 %), breast cancer (20 %) and melanoma (20 %), and the median tumor diameter was 1.7 cm (range 0.4–6.4 cm). Median survival after SRT was 10.7 months. Median time to local progression was 17 months, with a local control rate of 68 % at 6 months and 56 % at 1 year. Acute toxicity was seen in 11 patients (16 %), mostly grade 1 or 2 with the most common symptom being mild headache. Symptomatic radiation-induced treatment change was seen on follow-up MRIs in three patients (4.3 %). SRT appears to be a safe and reasonably effective technique to treat brain metastases deemed less suitable for SRS, though dose intensification strategies may further improve local control.     

Outcome of three-fraction gamma knife radiosurgery for brain metastases according to fractionation scheme: preliminary results

Journal of Neuro-Oncology - Chordoma is a rare refractory neoplasm that arises from the embryological remnants of the notochord, which is incurable using any multimodality therapy. Vascular...     

The rationale for adjuvant whole brain radiation therapy with radiosurgery in the treatment of single brain metastases

Randomized trials have established the efficacy of focal treatment (either stereotactic radiosurgery or conventional surgery) for single brain metastases. In the past, adjuvant whole brain radiation therapy (WBRT) was routinely given with focal therapy. Recently, the utility of adjuvant WBRT has been called into question. This paper examines the scientific evidence and the arguments, pro and con, concerning the use of adjuvant WBRT in association with stereotactic radiosurgery or conventional surgery.     

立体定向放疗与全脑放疗在多发脑转移瘤治疗中的作用分析

目的 总结立体定向放疗(SRT)加或不加全脑放疗(WBRT)治疗多发脑转移瘤的结果,探讨WBRT和SRT在多发脑转移瘤治疗中的作用。方法 1995—2010年收治的98例新诊断的多发(2~13个病灶)脑转移瘤患者。单纯SRT44例,WBRT加SRT54例。剂量分割模式依据转移瘤部位、体积及是否WBRT。用Kaplan-Meier法计算生存率,Cox回归模型进行各因素预后分析。中位生存期(MST)为从脑转移瘤放疗开始至各种原因所致死亡的时间的中位数。结果 全组患者中位随访时间12个月,随访率为100%。全组MST为13.5个月,其中SRT组、WBRT加SRT组的分别为13.0、13.5个月(χ²=0.31,P=0.578)。多因素分析显示仅卡氏评分(χ²=6.25,P=0.012)、原发灶诊断及脑转移瘤诊断间隔时间(χ²=7.34,P=0.025)和颅外病变情况(χ²=4.20,P=0.040)是预后因素。结论 SRT是多发脑转移瘤患者有效治疗手段,单纯SRT可取得与WBRT加SRT相似的生存期。首程SRT可能是多发脑转移瘤患者的另一治疗选择。     

分次伽玛刀治疗脑胶质瘤的近期疗效分析

目的:研究分次伽玛刀治疗脑胶质瘤的近期疗效.方法:2007年4月-2008年12月我科采用分次伽玛刀治疗脑胶质瘤37例,其中男性26例,女性11例,年龄最大85岁,最小11岁,中位年龄56岁,有明确病理诊断13例,影像诊断24例,肿瘤体积最大5.8cm×5.5cm×5.2cm,最小1.8cm×1.0cm×1.2cm.采用头膜固定,增强CT-SIM定位扫描,RTP S图像处理,影像学可见肿瘤为GTV ,GTV+水肿区为CTV,CTV+0.2cm为PTV,GTV平均体积:12.55cm3,PTV平均体积:15.83cm3.治疗模式:50%边缘等剂量曲线给予PTV 24Gy/3F或36Gy/6F,运用LUNATM-260伽玛射线立体定向回转聚焦放疗机实施治疗,根据患者病情1次/日或3次/周.结果:中位随访时间17个月,生存24例(24/ 37),其中2例治愈(CR),2例局控(PR),病情稳定16例,病情进展4例.死亡13例,总有效率50.4%,1年生存率42.0%,死亡病例的中位生存时间8个月,随访中未见严重不良反应及并发症. 结论:分次伽玛刀治疗脑胶质瘤近期疗效确切,不良反应及并发症较低,值得进一步扩大研究规模.