Stereotactic radiosurgery for patients with "radioresistant" brain metastases

OBJECTIVE: Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases that have been determined to be "radioresistant" on the basis of histological examination. METHODS: We reviewed the medical records of 41 consecutive patients who presented with 83 brain metastases from radioresistant primaries and subsequently underwent SRS. All patients were followed until death or for a median of 31 months after SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23 patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary metastasis, and 23 patients (56%) had multiple metastases. RESULTS: The median overall survival time was 14.2 months after SRS. On the basis of univariate analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P = 0.005) were associated with survival. The median survival time was 23.5 months for patients in RPA Class I status and 10.5 months for patients in RPA Class II or III status. There was a trend (P = 0.12) toward improved median survival for patients with renal cell carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo). Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of primary tumor (P < 0.001) to be independent predictors for overall survival. In the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred locally. In 54% of the patients, distant brain failure (DBF) developed. Whole brain radiotherapy (WBRT) improved local control and decreased DBF, according to the univariate and multivariate analyses. Patients who received adjuvant WBRT in addition to SRS had 6-month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Patients who received adjuvant WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of 64% among patients who had SRS alone (P = 0.0027). CONCLUSION: Well-selected patients with brain metastases from radioresistant primary tumors who undergo SRS survive longer than historical controls. RPA Class I status and primary renal cell carcinoma predict longer survival. Adjuvant WBRT improves local control and decreases DBF but does not affect overall survival. Further studies are needed to determine which patients should receive WBRT.     

Stereotactic radiosurgical treatment of parenchymal brain metastases from prostate adenocarcinoma

BACKGROUND: Prostate cancer metastatic to the brain is uncommon and has been associated historically with a poor prognosis. It has been suggested that SRS may be an effective treatment. METHODS: We analyzed a prospective, institutional review board-approved database of patients treated with SRS and identified 5 patients with prostate cancer metastasis. Clinical, pathologic, radiographic, treatment, and outcome information regarding the primary/systemic disease status, and brain metastases were collected. RESULTS: Mean age at the time of treatment for CNS parenchymal metastasis was 72.0 +/- 8.3 years and lesions developed 82.0 +/- 65.1 months after the initial tumor was identified. Four patients had a single lesion and 1 had 4; 3 patients were treated with SRS alone, 1 with WBRT and SRS, and 1 with surgery, then WBRT and SRS. All were symptomatic. Stereotactic radiosurgery controlled the brain metastases in all 5 patients, with functional improvement and with a typical increase of 1 grade in the Karnofsky performance score. Mean survival was at least 10.0 +/- 6.7 months (range, 6-22+ months). Two patients died of conditions unrelated to prostate cancer and 2 of systemic disease progression; 1is alive and asymptomatic. There were no local SRS failures and no new CNS lesions. CONCLUSIONS: Stereotactic radiosurgery for prostate cancer metastatic to the brain, alone or in combination with brain radiation therapy and surgery, is a safe, effective treatment that improves neurologic symptoms and function and may prolong survival.     

Novel prognostic classification predicts overall survival of patients receiving salvage whole-brain radiotherapy for recurrent brain metastasis from breast cancer: A recursive partitioning analysis (KROG 16-12)

BackgroundTo investigate outcomes of salvage whole-brain radiotherapy (WBRT) for recurrent brain metastases (BM) from breast cancer (BC), to identify prognostic factors of overall survival (OS), and to propose a novel prognostic classification for OS in these patients.Materials and methodsWe identified 54 patients who had received salvage WBRT as the second brain-focused treatment for recurrent BM from BC (2000–2014). The median follow-up duration was 4.9 months. A recursive partitioning analysis (RPA) was conducted to develop a model to predict OS at the time of salvage WBRT.ResultsThe median OS was 6.8 months. OS according to BC-specific graded prognostic assessment (breast-GPA), modified breast-GPA, and updated breast-GPA did not represent our cohort. In the multivariate analysis, a long time before salvage WBRT (≥16 months), control of primary BC or extracranial metastases, systemic treatment after salvage WBRT, and administration of a biologically effective dose for an α/β of 10 Gy (BED10) of salvage WBRT >37.5 Gy showed superior OS. We proposed three RPA classes based on the control of both primary BC and extracranial metastasis and BED10 of salvage WBRT: class I, class II, and class III. In this model, patients with class I experienced the best OS (34.6 months; class II, 5.0 months; class III, 2.4 months; P < 0.001).ConclusionsIn our RPA classification according to the control of both primary BC and extracranial metastasis and the dose of salvage WBRT, significant differences in OS were observed. The subsequent use of a systemic treatment showed better OS.     

Resection of brain metastases previously treated with stereotactic radiosurgery

OBJECT: To date, no report has been published on outcomes of patients undergoing resection for brain metastases who were previously treated with stereotactic radiosurgery (SRS). Consequently, the authors reviewed their institutional experience with this clinical scenario to assess the efficacy of surgical intervention. METHODS: Sixty-one patients (each harboring three or fewer brain lesions), who were treated at a single institution between June 1993 and August 2002 were identified. Patient charts and their neuroimaging and pathological reports were retrospectively reviewed to determine overall survival rates, surgical complications, and recurrence rates. A univariate analysis revealed that patient preoperative recursive partitioning analysis (RPA) classification, primary disease status, preoperative Karnofsky Performance Scale score, type of focal treatment undergone for nonindex lesions, and major postoperative surgical complications were factors that significantly affected survival (p < or = 0.05). In contrast, only the RPA class and focal (conventional surgery or SRS) treatment of nonindex lesions significantly (or nearly significantly) affected survival in the multivariate analysis. Major neurological complications occurred in only 2% of patients. The median time to distant recurrence after resection was 8.4 months; that to local recurrence was not reached. The overall median survival time was 11.1 months, with 25% of patients surviving 2 or more years. Conventional surgery facilitated tapering of steroid administration. Conclusions. The complication, morbidity, survival, and recurrence rates are consistent with those seen after conventional surgery for recurrent brain metastases. Our results indicate that in selected patients with a favorable RPA class in whom nonindex lesions are treated with focal modalities, surgery can provide long-term control of SRS-treated lesions and positively affect overall survival.     

The role of stereotactic radiosurgery for multiple brain metastases in stable systemic disease: a review of the literature

Background

Cancer patients with brain metastases display a median survival of only 1 to 2 months if left untreated. Although whole-brain radiation therapy (WBRT) has lengthened median patient survival, the long-term neurotoxic effects of WBRT have become a deterrent to its use in the context of stable systemic disease. Therefore, it is important to identify patients who might benefit from stereotactic radiosurgery (SRS) in order to delay or avoid WBRT. Here we present a review of the literature to elucidate the role of SRS in patients with multiple brain metastases.

Methods

MEDLINE search for English-language articles from 1998 to 2012 describing survival or neurocognitive functioning of patients with multiple brain metastases treated with SRS, WBRT, or a combination.

Results

SRS monotherapy yields an equivalent survival with low risk of long-term neurotoxicity, but higher rate of recurrence, compared to WBRT or combined radiotherapy. Patients with ≤4 brain metastases or KPS?≥?80 are expected to survive significantly longer than the onset time of prominent WBRT-induced neurocognitive decline.

Conclusions

SRS, administered alone or adjuvant to surgical resection of symptomatic metastases, is preferred for patients with ≤4 brain metastases or KPS?≥?80 to delay or avoid WBRT. WBRT can then be employed in the event of recurrence. WBRT with or without resection is preferred for patients with ≥5 brain metastases and KPS?<?80, due to these patients’ shorter survival and increased recurrence risk. SRS boost treatments can then be used in the event of poor tumor response or progression.     

Surgery of recurrent brain metastases: retrospective analysis of 67 patients

Objective

Treatment of patients with recurrent brain metastasis is one of the major challenges in neurooncology. Commonly, WBRT was applied after or as the initial treatment. Many patients received radiosurgery or their lesions were operated on. The question arises of what treatment modalities are appropriate and can be offered to the patients. In our retrospective analysis, we evaluated whether re-operation might be a useful measurement for the patients with respect to overall survival and quality of life.

Methods

We included 67 patients who were treated between 1993 and 2008 in our department. The median age was 59 years. Metastases of 11 different primaries were diagnosed. The median OST was 7.5 months.

Results

Statistically significant prognostic factors for OS were single lesions, completeness of resection, and time to recurrence, which was significantly influenced by WBRT after first operation. The one year survival rate correlated with the RPA classification: class I: 53.3 %, class II: 26.9 %, class III: 12.5 %. In 31.3 %, a second recurrence occurred which was treated by repeated surgery. Six patients survived as long-term survivors (25.7–132.2 months).

Conclusion

Surgery of recurrent brain metastasis is an important therapeutic option. A subgroup of patients, defined by prognostic factors, will profit with improvement of symptoms and prolongation of the overall survival time. Even long-term survivors can be expected.     

Stereotactic radiosurgery without radiation therapy providing high local tumor control of multiple brain metastases from renal cell carcinoma.

The aim of this study was to analyse treatment effects after stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) as primary treatment for patients harboring brain metastases of renal cell carcinoma (RCC). During an 8-year period, 85 patients with 376 brain metastases from RCC underwent 134 outpatient SRS procedures. 65 % of all patients had multiple brain metastases. The median tumor volume was 1.2 cm (3) (range: 0.1 - 14.2 cm (3)). Mean prescribed tumor dose was 21.2 (+/- 3.2) Gy. Local/distant tumor recurrences were treated by additional SRS in cases of stable systemic disease. Overall median survival was 11.1 months after SRS. The local tumor control rate after SRS was 94 %. Most patients (78 %) died because of systemically progressing cancer. A KPS > 70 and RTOG class I were related to prolonged survival time. Patients of the RTOG groups I, II and III survived for 24.2 months, 9.2 months and 7.5 months, respectively. There was no permanent morbidity after SRS. 11 patients (12.9 %) showed transient radiogenic complications and 3 patients (3.5 %) died because of intratumoral bleedings after SRS. Stereotactic radiosurgery alone achieves excellent local tumor control rates for patients with small brain metastases from renal cell carcinoma.     

Brain metastases

Metastatic brain tumors are the most common intracranial neoplasm in adults, affecting up to 10% of adults with cancer in the United States. The risk of developing brain metastases varies by primary cancer type, with lung cancer, breast cancer, and melanoma accounting for the majority. The incidence of brain metastases appears to be rising because of several factors, including an aging population, better treatment of systemic disease, and improved cranial imaging techniques. Therapeutic approaches to brain metastases include surgery, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and chemotherapy. Many patients are treated with a combination of these, and treatment decisions must take into account clinical prognostic factors in order to maximize survival and neurologic function while avoiding unnecessary treatments. WBRT remains the most widely used treatment for patients with brain metastases. Although many radiation sensitizers have been studied over the years, none has emerged for widespread use. For patients with a limited number of brain metastases and favorable prognostic factors, local therapies such as surgery and SRS improve control rates and may extend survival compared with WBRT alone. SRS can also be used effectively at recurrence in patients with a limited number of lesions. Chemotherapy has traditionally played only a salvage role for brain metastases when all other treatments have failed, but research is likely to increasingly focus on systemic options such as targeted agents and angiogenesis inhibitors, as well as on novel delivery techniques and multidrug resistance pathways specific to brain in order to expand treatment options for this growing population of patients.     

Prognostic factors in patients treated with stereotactic image-guided robotic radiosurgery for brain metastases: a single-center retrospective analysis of 223 patients

In this retrospective study, we evaluated the overall survival (OS) and local control (LC) of brain metastases (BM) in patients treated with stereotactic radiosurgery (SRS). The scope was to identify host, tumor, and treatment factors predictive of LC and survival and define implications for clinical decisions. A total of 223 patients with 360 BM from various histologies treated with SRS alone or associated with whole brain radiotherapy (WBRT) in our institution between July 1, 2008 and August 31, 2013 were retrospectively reviewed. Among other prognostic factors, we had also evaluated retrospectively Karnofsky performance status scores (KPS) and graded prognostic assessment (GPA). Overall survival (OS) and local control (LC) were the primary endpoints. Kaplan-Meier and Cox proportional hazards models were used to estimate OS and LC and identify factors predictive of survival and local control. The median duration of follow-up time was 9 months (range 0.4–51 months). Median overall survival of all patients was 11 months. The median local control was 38 months. No statistical difference in terms of survival or LC between patients treated with SRS alone or associated with WBRT was found. On multivariate analysis, KPS was the only statistically significant predictor of OS (hazard ratio [HR] 2.53, p?=?0.006). On univariate analysis, KPS and GPA were significantly prognostic for survival. None of the host, tumor, or treatment factors analyzed in the univariate model factors were significantly associated with local failure.     

Retrospective study of 127 surgically treated patients with multiple brain metastases: indication, prognostic factors, and outcome

Background

Metastases are the most frequent tumours in the brain. At the time of diagnosis, more than 50% of patients present with multiple lesions. The goal of our retrospective investigation was to evaluate the outcome of patients who undergo surgery for multiple cerebral metastases and to determine prognostic factors.

Methods

We included 127 patients with multiple brain metastases in the study. The median number of metastases was three. All patients were operated on for at least one lesion. The indications for surgery were: large tumours ≥27 cm³, metastases of unknown primaries at the time of diagnosis, and space-occupying cerebellar lesions. If possible, adjuvant WBRT was applied.

Results

The median MST of the whole group was 6.5 months; for patients with complete resection, 10.6 months. According to the RPA classification the MST ranged between 19.4 (class I), 7.8 (class II), and 3.4 months (class III) (p < 0.001). KPS?>?70 had a significant influence on MST (9.1 months vs. 3.4 months, p?<?0.001), the number of lesions: 2–4 vs. >4 (p?=?0.046), and postoperative WBRT in multivariate analysis (p?=?0.026). Age was not a significant factor. The 2-year survival rate was 15% and the 3-year survival rate 10%.

Conclusions

Favourable factors for prolonged survival were complete resection of all lesions, no more than four metastases, RPA-class I and adjuvant WBRT. The resection of large lesions, while leaving smaller residual ones, did not result in increased survival.     

The expanding role of neurosurgeons in the management of brain metastases

BACKGROUND: Brain metastases are the most common type of intracranial tumor. Until recently, whole brain fractionated radiation therapy (WBRT) was the mainstay of treatment, thereby confining the role of neurosurgeons to resection of an occasional solitary, accessible, and symptomatic brain metastasis. Median survival after surgery and radiation typically ranged from 5 to 11 months. METHODS: We analyzed various demographic incidence reports and our series of brain metastasis patients treated with radiosurgery. During a 15-year interval (1987-2002), radiosurgery was performed on 5,032 patients of whom 1,088 (21.6%) had metastatic brain tumors. RESULTS: In the United States, 266,820 to 533,640 new cases of brain metastases will be diagnosed in the year 2003. Evidence to date demonstrates that radiosurgery provides effective local tumor control for brain metastases. Important prognostic factors affecting patient survival include the absence of active systemic disease, the patient's preoperative performance status, age, and the number of metastases. Survival and local tumor control rates attained with radiosurgery are superior to those of either conventional surgery or WBRT. The morbidity associated with radiosurgery of brain metastasis is very low, and the mortality rate approaches zero. CONCLUSIONS: Compelling evidence indicates that radiosurgery is an effective neurosurgical management strategy for intracranial brain metastases. Quite often, favorable tumor control and survival can be achieved without WBRT. With radiosurgery as a therapeutic option, neurosurgeons now have a vastly expanded armamentarium for treatment of patients with brain metastases. The large number of patients with brain metastases who require care by a neurosurgeon for optimal treatment has significant implications for both the patterns of neurosurgical training and practice in the United States.     

大肠癌脑转移的临床特征及其手术治疗

目的 分析大肠癌脑转移的临床特征及其手术治疗转归. 方法回顾性分析手术治疗的大肠癌伴脑转移28例患者的临床资料,统计数据采用单因素Log-Rank分析和多因素Cox回归分析法.结果 大肠癌继发脑转移的中位年龄为57(41～75)岁,原发肿瘤与转移瘤间隔的中位时间为13.5个月,其中合并颅外(肺、肝、骨)转移占61%(17/28),仅有脑转移的占39%(11/28).脑转移瘤主要表现为头痛、呕吐等颅内压升高征候群和偏瘫、下肢乏力、失语等定位症状以及癫痫等,颅内转移瘤以单发病灶为多见,占82%(23/28),位于幕上(枕叶、顶叶、额叶)者占57%(16/28),位于幕下(小脑)者占43%(12/28);转移性脑瘤手术切除后中位生存时间为9.4个月,1年生存率为28.9%,5年生存率为7.1%.多因素分析提示颅内单发病灶转移(χ2=7.35,P<0.05)和无颅外其他部位转移(χ2=6.47,P<0.05)是大肠癌脑转移预后的独立影响因素.28例均接受手术切除和多学科协作治疗,无手术死亡和出血及再手术病例.结论 大肠癌脑转移总体预后欠佳,手术切除脑转移病灶可延长部分患者的存活时间.     

大肠癌脑转移的临床特征及其手术治疗

目的 分析大肠癌脑转移的临床特征及其手术治疗转归. 方法回顾性分析手术治疗的大肠癌伴脑转移28例患者的临床资料,统计数据采用单因素Log-Rank分析和多因素Cox回归分析法.结果 大肠癌继发脑转移的中位年龄为57(41～75)岁,原发肿瘤与转移瘤间隔的中位时间为13.5个月,其中合并颅外(肺、肝、骨)转移占61%(17/28),仅有脑转移的占39%(11/28).脑转移瘤主要表现为头痛、呕吐等颅内压升高征候群和偏瘫、下肢乏力、失语等定位症状以及癫痫等,颅内转移瘤以单发病灶为多见,占82%(23/28),位于幕上(枕叶、顶叶、额叶)者占57%(16/28),位于幕下(小脑)者占43%(12/28);转移性脑瘤手术切除后中位生存时间为9.4个月,1年生存率为28.9%,5年生存率为7.1%.多因素分析提示颅内单发病灶转移(χ2=7.35,P<0.05)和无颅外其他部位转移(χ2=6.47,P<0.05)是大肠癌脑转移预后的独立影响因素.28例均接受手术切除和多学科协作治疗,无手术死亡和出血及再手术病例.结论 大肠癌脑转移总体预后欠佳,手术切除脑转移病灶可延长部分患者的存活时间.     

大肠癌脑转移的临床特征及其手术治疗

目的 分析大肠癌脑转移的临床特征及其手术治疗转归. 方法回顾性分析手术治疗的大肠癌伴脑转移28例患者的临床资料,统计数据采用单因素Log-Rank分析和多因素Cox回归分析法.结果 大肠癌继发脑转移的中位年龄为57(41～75)岁,原发肿瘤与转移瘤间隔的中位时间为13.5个月,其中合并颅外(肺、肝、骨)转移占61%(17/28),仅有脑转移的占39%(11/28).脑转移瘤主要表现为头痛、呕吐等颅内压升高征候群和偏瘫、下肢乏力、失语等定位症状以及癫痫等,颅内转移瘤以单发病灶为多见,占82%(23/28),位于幕上(枕叶、顶叶、额叶)者占57%(16/28),位于幕下(小脑)者占43%(12/28);转移性脑瘤手术切除后中位生存时间为9.4个月,1年生存率为28.9%,5年生存率为7.1%.多因素分析提示颅内单发病灶转移(χ2=7.35,P<0.05)和无颅外其他部位转移(χ2=6.47,P<0.05)是大肠癌脑转移预后的独立影响因素.28例均接受手术切除和多学科协作治疗,无手术死亡和出血及再手术病例.结论 大肠癌脑转移总体预后欠佳,手术切除脑转移病灶可延长部分患者的存活时间.     

Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy?

OBJECTIVE: Whole brain radiotherapy (WBRT) provides benefit for patients with brain metastases but may result in neurological toxicity for patients with extended survival times. Stereotactic radiosurgery in combination with WBRT has become an important approach, but the value of WBRT has been questioned. As an alternative to WBRT, we managed patients with stereotactic radiosurgery alone, evaluated patients' outcomes, and assessed prognostic factors for survival and tumor control. METHODS: One hundred seventy-two patients with brain metastases were managed with radiosurgery alone. One hundred twenty-one patients were evaluable with follow-up imaging after radiosurgery. The median patient age was 60.5 years (age range, 16-86 yr). The mean marginal tumor dose and volume were 18.5 Gy (range, 11-22 Gy) and 4.4 ml (range, 0.1-24.9 ml). Eighty percent of patients had solitary tumors. RESULTS: The overall median survival time was 8 months. The median survival time in patients with no evidence of primary tumor disease or stable disease was 13 and 11 months. The local tumor control rate was 87%. At 2 years, the rate of local control, remote brain control, and total intracranial control were 75, 41, and 27%, respectively. In multivariate analysis, advanced primary tumor status (P = 0.0003), older age (P = 0.008), lower Karnofsky Performance Scale score (P = 0.01), and malignant melanoma (P = 0.005) were significant for poorer survival. The median survival time was 28 months for patients younger than 60 years of age, with Karnofsky Performance Scale score of at least 90, and whose primary tumor status showed either no evidence of disease or stable disease. Tumor volume (P = 0.02) alone was significant for local tumor control, whereas no factor affected remote or intracranial tumor control. Eleven patients developed complications, six of which were persistent. Nineteen (16.5%) of 116 patients in whom the cause of death was obtained died as a result of causes related to brain metastasis. CONCLUSION: Brain metastases were controlled well with radiosurgery alone as initial therapy. We advocate that WBRT should not be part of the initial treatment protocol for selected patients with one or two tumors with good control of their primary cancer, better Karnofsky Performance Scale score, and younger age, all of which are predictors of longer survival.     

Treatment for brain metastasis from lung cancer in the era of radiosurgery

OBJECTIVE: The treatment for brain metastasis has undergone remarkable changes since the development of radiosurgery. We investigated the results of treatment for brain metastasis from lung cancer since the initiation of gamma knife radiosurgery (GKRS) and we discuss the usefulness of GKRS combined with other treatments in cases with recurrence. METHODS: We treated 142 patients with brain metastasis from lung cancer. Sixteen patients were treated surgically, 11 patients were treated with whole brain radiation therapy (WBRT), and 115 patients were treated with GKRS. Our treatment plan is to use GKRS in cases with less than 5 lesions and lesions less than 3 cm in mean diameter. We use WBRT in cases with 5 or more lesions, and surgery in cases with lesions 3 cm or larger. If new lesions or tumor regrowth appeared after the initial treatment, we retreated them with one of the methods mentioned above. RESULTS: Twice or three-time treatments were performed in 30 patients. Median survival including all cases was 10 months and the number of deaths due to local treatment failure was only 5 (6.5%) out of the total 77 deaths which occurred. CONCLUSION: We were able to carry out less invasive treatment for brain metastasis from lung cancer by utilizing GKRS. Though we have to consider the indications for other treatments, we can say that radiosurgery is usually the treatment of first choice for brain metastasis from lung cancer. When new lesions appear in cases where a particular initial treatment was used, it is possible to maintain or improve the quality of life by retreatment, using a combination of GKRS, surgery or WBRT, to prolong the patient's life.     

Brain metastasis in patients with esophageal carcinoma

BACKGROUND: Brain metastasis from esophageal carcinoma is rare, and its natural history is unclear. To determine predictors for their outcomes, we conducted a retrospective review of patients. METHODS: We treated 803 patients with metastatic brain tumors, and there were 17 patients with brain metastases from esophageal carcinoma. Their median age at the diagnosis was 57 years. RESULTS: In the 15 patients with the pretreatment KPS of 70 or higher, the median survival after the diagnosis of brain metastasis was 26.2 months. Seven patients showed the median survival of 17.7 months after resection alone. The median survival was 65.5 months in the 3 patients who were treated with resection plus radiation. CONCLUSIONS: Neurosurgical resection followed by WBRT seemed to be the indicated treatment in these patients.     

Hypofractionated stereotactic radiotherapy using intensity-modulated radiotherapy in patients with one or two brain metastases

PURPOSE: A small fraction of patients with 1-2 brain metastases will not be suitable candidates to either surgical resection or stereotactic radiosurgery (SRS) due to either their location or their size. The objective of this study was to determine the local control, survival, patterns of relapse and the incidence of brain injury following a course of hypofractionated stereotactic radiotherapy while avoiding upfront whole brain radiation therapy (WBRT) in this subgroup of patients. METHODS: A Gill-Thomas removable head frame system was used for immobilization. Brain LAB software with dynamic multileaf collimator hardware was used to design and deliver an intensity-modulated radiation therapy treatment plan. A dose of 600 cGy was prescribed to the 100% isodose line that would encompass the lesion with a 3-mm margin. A total dose of 3,000 cGy was delivered in 5 fractions using 2 fractions per week. The patients were followed with neurological examination and serial MRI images done every 3 months following the procedure. RESULTS: Twenty patients have been treated using this fractionation schedule since April 2004. The 1-year local control at the site of original disease is 70%. The complete response, partial response and stable disease at the last follow-up were 15, 30 and 45%, respectively. Two patients had local recurrence at the site of original disease, while 5 had evidence of leptomeningeal disease. Two additional patients developed new brain metastases, resulting in a 1-year brain relapse-free survival of 36% following this approach. The median overall survival was 8.5 months. Three patients (15%) developed steroid dependency lasting 3 months or longer following the procedure. Four patients (20%) needed WBRT as salvage following this approach. CONCLUSIONS: The preliminary results of hypofractionated SRS are comparable to both surgery and SRS data for solitary brain metastases in terms of local control and overall survival with acceptable morbidity in this cohort of unfavorable patients.     

Brain metastasis from non-seminomatous germ cell tumors of the testis

Brain metastases from non-seminomatous germ cell tumors (NSGCTs) are rare and mainly occur in young men whose clinical condition is unimpaired. The records of 15 patients with brain metastasis from non-seminomatous germ cell tumors of the testis, who had been surgically treated between 1984 and 1998, were retrospectively reviewed. All of the patients had undergone surgery plus whole-brain radiotherapy (WBRT), and chemotherapy based on cisplatin. On admission they had a median age of 33 years and their mean Karnofsky performance scale (KPS) score was >70. Mean survival was 37.7 months. Eight patients had a survival period longer than 5 years. Five patients belonged to radiation therapy oncology group (RTOG) class I; all of them survived. There was a significant difference in survival time between patients in whom the brain metastasis was present at diagnosis (six survivors at 5 years; mean survival 53 months) and patients in whom the brain metastasis occurred during or after chemotherapy (two survivors at 5 years; mean survival 24 months) (P=0.04). The presence of a trophoblastic component at histopathological analysis of the metastasis negatively influenced survival at univariate analysis. Multiple brain metastasis proved to be a significant risk factor at both univariate and multivariate analysis, while a metastatic residue with a diameter less than 2 cm after surgery did not negatively affect survival in our series. Prognosis is worst in patients with multiple brain metastases, in whom brain involvement occurred during or after cisplatin-based chemotherapy. Considering that these metastases are often both radiosensitive and chemosensitive, and mainly affect young men that are in very good clinical condition, we advocate aggressive treatment with surgery plus adjuvant radiotherapy and chemotherapy. This is mandatory in patients with large metastases (diameter >3 cm).     

Stereotactic Radiosurgery for Patients with Single Brain Metastasis

The efficacy of stereotactic radiosurgery (SRS) was evaluated for patients with single brain metastasis from extracranial primary cancer and the outcome was compared with that of external whole brain irradiation (WBI) alone or with surgical resection. Between January 1976 and December 1996, 225 patients with single brain metastases were treated in the Department of Therapeutic Radiology—Radiation Oncology at the University of Minnesota Hospital. One hundred six patients (47%) were treated with WBI alone (Group 1), 71 patients (32%) underwent surgical resection prior to WBI (Group 2), and 48 patients (21%) underwent SRS ± WBI (Group 3). The most common site of primary cancer was the lung (40%), followed by breast (14%), unknown primary (11%), skin (malignant melanoma, 9%), gastrointestinal tract (8%), kidney (renal cell carcinoma, 8%), gynecological organs (3%), and other (6%). Median dose to the whole brain was 3750 cGy in 15 fractions (range, 2000–5000 cGy). Median radiosurgical dose of 1750 cGy (range, 1200–4000 cGy) was delivered to the 40 to 90% isodose line encompassing the target. Actuarial survival was calculated from the date of treatment using the Kaplan–Meier method and statistical significance was assessed with the log-rank test. Actuarial median survival was 3.8 months for Group 1 (range, 1–84 months), 10.5 months for Group 2 (range, 1–125 months), and 9.8 months for Group 3 (range, 1–51 months). Survival at 1 and 2 years was 20% and 8% for Group 1, 47% and 18% for Group 2, and 37% and 27% for Group 3, respectively. Group 2 (surgery + WBI) and Group 3 (SRS ± WBI) had a statistically significant survival advantage over Group 1 (WBI alone) (p < 0.0001, log-rank test). No survival advantage was found between Groups 2 and 3 (p = 0.69, log-rank test). Our retrospective data suggest that SRS (± WBI) improves survival when compared to WBI alone and is comparable to surgical resection and WBI. Given that SRS is minimally invasive, is able to treat lesions in surgically inaccessible locations, and is potentially more cost-effective than surgery, it is a reasonable and potentially more attractive alternative to surgery in the management of single brain metastasis.