Multimodality treatment of melanoma brain metastases incorporating stereotactic radiosurgery (SRS)

BACKGROUND: Brain metastases are a frequent complication in advanced melanoma. A 3.6 to 4.1-month median survival has been reported after treatment with whole brain radiotherapy. We performed a retrospective analysis of our institutional experience of multimodality treatment utilizing linear accelerator (Linac)-based stereotactic radiosurgery (SRS). METHODS: Forty-four melanoma patients with brain metastases underwent 66 SRS treatments for 156 metastatic foci between 1999 and 2004. Patients were treated with initial SRS if or=70, but 37 patients had active systemic metastases (Recursive Partition Analysis Class 2). Survival was calculated from the time of diagnosis of brain metastases. Minimum follow-up was 1 year after SRS. The potential role of prognostic factors on survival was evaluated including age, sex, interval from initial diagnosis to brain metastases, surgical resection, addition of whole brain radiotherapy (WBRT), number of initial metastases treated, and number of SRS treatments using Cox univariate analysis. RESULTS: The median survival of melanoma patients with brain metastases was 11.1 months (95% confidence interval [CI]: 8.2-14.9 months) from diagnosis. One-year and 2-year survivals were 47.7% and 17.7%, respectively. There was no apparent effect of age or sex. Surgery or multiple stereotactic radiotherapy treatments were associated with prolonged survival. Addition of WBRT to maintain control of brain metastases in a subset of patients did not improve survival. CONCLUSIONS: Our results suggest that aggressive treatment of patients with up to 5 melanoma brain metastases including SRS appears to prolong survival. Subsequent chemotherapy or immunotherapy after SRS may have contributed to the observed outcome.     

Radiotherapy and chemotherapy of brain metastases

Summary The authors have reviewed the results, the indications and the controversies regarding radiotherapy and chemotherapy of patients with newly diagnosed and recurrent brain metastases. Whole-brain radiotherapy, radiosurgery, hypofractionated stereotactic radiotherapy, brachytherapy and chemotherapy are the available options. New radiosensitizers and cytotoxic or cytostatic agents are being investigated. Adjuvant whole brain radiotherapy, either after surgery or radiosurgery, and prophylactic cranial irradiation in small-cell lung cancer are discussed, taking into account local control, survival, and risk of late neurotoxicity. Increasingly, the different treatments are tailored to the different prognostic subgroups, as defined by Radiation Therapy Oncology Group RPA Classes.     

Multidisciplinary management of brain metastases

Metastatic brain tumors are the most common intracranial neoplasms in adults. The incidence of brain metastases appears to be rising as a result of superior imaging modalities, earlier detection, and more effective treatment of systemic disease. Therapeutic approaches to brain metastases include surgery, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and chemotherapy. Treatment decisions must take into account clinical prognostic factors in order to maximize survival and neurologic function whilst avoiding unnecessary treatments. The goal of this article is to review important prognostic factors that may guide treatment selection, discuss the roles of surgery, radiation, and chemotherapy in the treatment of patients with brain metastases, and present new directions in brain metastasis therapy under active investigation. In the future, patients will benefit from a multidisciplinary approach focused on the integration of surgical, radiation, and chemotherapeutic options with the goal of prolonging survival, preserving neurologic and neurocognitive function, and maximizing quality of life.     

A comparison of survival rates for treatment of melanoma metastatic to the brain

Introduction: A retrospective review of 91 patients with brain metastases from malignant melanoma treated at New York University Medical Center between 1989-1999. Overall survival was the outcome evaluated. Methods: Charts of 91 patients having malignant melanoma with brain metastases were reviewed. Cases were stratified according to therapy: surgical excision, surgical excision plus whole brain radiation therapy, gamma knife stereotactic radiosurgery, gamma knife stereotactic radiosurgery plus whole brain radiation therapy, and whole brain radiation therapy alone. Patients treated with gamma knife stereotactic radiosurgery plus radiation therapy were combined with patients treated with surgical excision plus radiation therapy and compared to those treated with radiation therapy alone. Prognostic characteristics of the two groups were compared and survival curves were generated using the Kaplan-Meier method. The Cox proportional hazards model was used to control for prognostic factors that differed between the groups. Results: Patients treated with gamma knife stereotactic radiosurgery or surgical excision plus radiation therapy were younger, less likely to present with symptoms, and presented with fewer metastases to the brain than patients treated with radiation therapy alone. A survival benefit of 7.3 months (p = 0.05) was found to be associated with gamma knife radiosurgery or surgical excision plus radiation therapy over radiation therapy alone after controlling for differences in age, number of brain lesions, and presence of symptoms. Discussion: This retrospective study of 91 patients treated for melanoma metastases to the brain attempts to examine the effectiveness of different treatments in prolonging survival. Our results suggest that surgical excision or stereotactic radiosurgery with gamma knife in addition to radiation therapy may be more effective than radiation alone at prolonging survival for patients with a limited number of brain lesions. Conclusion: Survival of patients with melanoma metastases to the brain may be prolonged by treatment with gamma knife stereotactic radiosurgery or surgical excision plus whole brain radiation therapy.     

X射线立体定向放射治疗多发脑转移瘤的价值

目的　探讨X射线立体定向放射治疗多发脑转移瘤的疗效。方法　在 4种预后因素(年龄、治疗前卡氏评分、有无其他部位转移及转移灶数目 )相同或相似的条件下 ,配对选择两组病例。X射线立体定向放射治疗加常规放射治疗组 (研究组 )和常规放射治疗组 (对照组 )各 53例。在研究组中 ,X射线立体定向放射治疗采用单次照射 40例 ,分次照射 1 3例 ;单次靶区平均周边剂量为 2 0Gy,分次照射剂量为 4～ 1 2Gy/次 ,2次 /周 ,总剂量为 1 5～ 30Gy。X射线立体定向放射治疗结束后即开始全脑放射治疗。对照组采用全脑照射 30～ 40Gy,3～ 4周。结果　研究组和对照组中位生存期分别为1 1 .6、6 .7个月 (P <0 .0 5) ;1年生存率分别为 44 .3 %、1 7.1 % (P <0 .0 1 ) ;1年局部控制率分别为50 .9%、1 3 .2 % (P <0 .0 5) ;治疗后 1个月卡氏评分增加者分别占 69.8%、30 .2 % (P <0 .0 1 ) ;治疗后 3个月影像学上的有效率分别为 82 .0 %、55 .0 % (P <0 .0 1 )。在死因分析中 ,研究组死于脑转移的占2 3 .3 % ,比对照组的 51 .0 %低 (P <0 .0 5)。两组病例放射并发症的发生率相似。结论　对于多发脑转移瘤 ,X射线立体定向放射治疗加常规放射疗在提高局部控制率、延长生存期和提高生存质量方面均优于单纯放射治疗。     

The role of chemotherapy in the treatment of patients with brain metastases from solid tumors

Brain metastases are the most frequent cancer in the central nervous system, being ten times more common than primary brain tumors. Patients generally have a poor outcome with a median survival of 4 months after diagnosis of the metastases. Therapeutic options include surgery, stereotactic, radiosurgery, whole-brain radiotherapy (WBRT), and chemotherapy. Patients with a limited number of brain metastases and well-controlled systemic cancer benefit from brain metastases-specific therapies, including surgery, radiosurgery, and conventional radiation. The role of chemotherapy for brain metastases remains limited. There is concern about drug delivery because of the blood-brain barrier. However, higher response rates are noted with initial therapies, suggesting that part of the poor response rate may be related to the late onset of brain metastases and the use of second- and third-line regimens. Recent studies have demonstrated objective responses with systemic therapy in a variety of cancer types, especially when combined with WBRT. Individual therapeutic strategies for central nervous system metastases must be chosen based on performance status, the extent of intracranial disease, and the chemosensitivity of the underlying tumor, as well as the control of the systemic cancer. In this article we review important prognostic factors and challenges in using chemotherapy. We specifically review recent advances in the treatment of brain metastases from breast and lung cancer as well as melanoma. Future treatment advances will require a multidisciplinary approach integrating surgical, radiation, and chemotherapeutic options to improve neurological function and quality of life, rather than just focusing on survival endpoints.     

Stereotactic radiosurgery for cerebral metastatic melanoma: factors affecting local disease control and survival

Purpose: The development of a brain metastasis represents an ominous event for patients with malignant melanoma. We evaluated results after stereotactic radiosurgery (SR) for patients with metastastic melanoma to identify patient outcomes and factors for survival.Methods: The authors reviewed the management results of 60 consecutive patients with melanoma metastases, with a total of 118 melanoma brain metastases, undergoing SR during a 9-year interval. Of these, 51 also had whole-brain radiation therapy (WBRT). A total of 118 tumors of mean volume of 2.95 ml (range, 0.1–25.5 ml) were treated by SR with a mean margin dose of 16.4 Gy (range, 10 to 20 Gy). Univariate and multivariate analyses were used to determine significant prognostic factors affecting survival in 60 patients.Results: Median survival was 7 months after SR in all 60 patients and 10 months from brain tumor diagnosis (mean follow-up period, 9.3 months). Lack of active systemic disease and a solitary metastasis were associated with improved survival in multivariate analysis (median, 15 months). The imaging-defined local control rate of evaluable tumors (n = 72) was 90% (disappearance = 11%, shrinkage = 44%, and stable = 35%). Local recurrence developed in 7 patients and remote brain disease developed in 14 patients. WBRT combined with radiosurgery did not improve survival nor local tumor control. New brain metastases developed less often when WBRT was added to SR (23% vs. 44%), but this difference was not significant. Only 4 patients (7%) died from progression of a radiosurgery-managed tumor. No patient developed a delayed radiation-related complication, but 3 patients developed delayed intratumoral hemorrhage at the radiosurgery site, 2 of whom had new symptoms.Conclusions: Stereotactic radiosurgery for melanoma brain metastasis is effective and is associated with few complications. The use of radiosurgery alone is an appropriate management strategy for many patients with solitary tumors.     

Treatment of melanoma brain metastases: a new paradigm

Brain metastases occur commonly in patients with metastatic melanoma, are associated with a poor prognosis, and cause significant morbidity. Both surgery and stereotactic radiosurgery are used to control brain metastases and, in selected patients, improve survival. In those with extensive brain involvement, whole-brain radiotherapy can alleviate symptoms. Historically, systemic therapy has had little role to play in the management of melanoma brain metastases; however, early clinical trials of BRAF inhibitors have shown promising activity. This review examines the evidence for local and systemic treatments in the management of patients with melanoma brain metastases. We present a new treatment algorithm for melanoma patients with brain metastases, which integrates the evolving evidence for the use of BRAF inhibitors.     

Treatment options for brain metastases in patients with non-small cell lung cancer

Opinion statement Brain metastases are a common complication for patients with non-small cell lung cancer and a significant cause of morbidity and mortality. In the past, treatment of brain metastases and lung cancer focused on symptom palliation with whole brain radiotherapy (WBRT) and steroids because of the grim outlook for patients. However, recent advances in technology and surgical techniques have created more options for the management of brain metastases, which include surgery, irradiation, stereotactic radiosurgery, and chemotherapy. These aggressive approaches have resulted in an improvement of neurologic outcomes and survival rates of patients with non-small cell lung cancer. Central nervous system (CNS) metastases can be divided into three groups: solitary CNS metastases with controlled or controllable primary disease, oligometastatic disease (fewer than three metastases), and multiple metastases. For patients with solitary CNS metastases, long-term survival is possible. A radical treatment approach involving surgical resection or radiosurgery, followed by WBRT, is recommended. For patients with oligometastatic disease, surgical resection or radiosurgery is considered in selected cases and WBRT is indicated. For patients with multiple metastases, WBRT is recommended. For patients with oligometastatic disease and patients with multiple metastases, recent evidence indicates that systemically effective chemotherapy may produce responses and can be instituted safely before radiotherapy. The treatment timing of chemotherapy and radiotherapy should be individualized.     

食管癌根治术后复发的治疗策略

  目的  探讨食管癌根治性切除术后复发患者的放射治疗策略和预后因素。  方法  回顾性分析病理确诊为食管癌且经R0切除后出现复发转移的66例患者,肿瘤中位复发时间10.6个月;50例患者局部区域复发,16例患者复发合并远处转移;全组患者中,单纯放疗10例,单纯化疗23例,放化联合治疗33例;联合放化疗组:先行化疗者22例,先行放疗者11例。放疗采用6MV-X线,中位放疗剂量60 Gy。  结果  全组患者1、2、3年生存率和中位生存时间分别为61.9%、25.9%、16.5%和14.3个月（95% CI=2.4~16.2个月）。三种治疗模式中单纯化疗、单纯放疗和联合放化疗的患者中位生存时间分别为11.4、25.5和14.3个月（P= 0.037）。复发合并远处转移的联合放化疗患者,先行化疗较先行放疗生存有获益（P=0.032）。单因素分析显示患者初治时的肿瘤分段、术式、复发是否合并转移、复发后治疗方式以及复发后是否放疗与患者预后相关（P < 0.05）。多因素分析显示患者初始治疗时的肿瘤分段为影响患者预后的独立因素（P < 0.01）。  结论  术前食管癌分段或许能提示复发的预后;对于有远处转移的患者,先行化疗后再放疗,对延长生存更有益。      

Stereotactic radiosurgery for four or more intracranial metastases

PURPOSE: To evaluate the outcomes after a single stereotactic radiosurgery procedure for the care of patients with 4 or more intracranial metastases. METHODS AND MATERIALS: Two hundred five patients with primary malignancies, including non-small-cell lung carcinoma (42%), breast carcinoma (23%), melanoma (17%), renal cell carcinoma (6%), colon cancer (3%), and others (10%) underwent gamma knife radiosurgery for 4 or more intracranial metastases at one time. The median number of brain metastases was 5 (range, 4-18) with a median total treatment volume of 6.8 cc (range, 0.6-51.0 cc). Radiosurgery was used as sole management (17% of patients), or in combination with whole brain radiotherapy (46%) or after failure of whole brain radiotherapy (38%). The median marginal radiosurgery dose was 16 Gy (range, 12-20 Gy). The mean follow-up was 8 months. RESULTS: The median overall survival after radiosurgery for all patients was 8 months. The 1-year local control rate was 71%, and the median time to progressive/new brain metastases was 9 months. Using the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) classification system, the median overall survivals for RPA classes I, II, and III were 18, 9, and 3 months, respectively (p < 0.00001). Multivariate analysis revealed total treatment volume, age, RPA classification, and marginal dose as significant prognostic factors. The number of metastases was not statistically significant (p = 0.333). CONCLUSION: Radiosurgery seems to provide survival benefit for patients with 4 or more intracranial metastases. Because total treatment volume was the most significant predictor of survival, the total volume of brain metastases, rather than the number of metastases, should be considered in identifying appropriate radiosurgery candidates.     

Melanoma in the brain: biology and therapeutic options

The development of brain metastases is a frequent occurrence in patients with disseminated melanoma and contributes to a disproportionate degree of morbidity and mortality. The prognosis is markedly reduced once a patient is diagnosed with central nervous system disease. Definitive therapeutic interventions with resection or stereotactic radiosurgery have improved outcomes and become standard approaches in the management of melanoma brain metastases. With the inclusion of whole-brain radiation in these interventions, there has been a reduction in local recurrences, but no improvement in the overall survival. Still, many patients are not candidates for surgery nor radiotherapy nor develop progressive central nervous system disease after definitive therapy. As new immune-based and targeted therapeutic agents are developed for the treatment of metastatic melanoma, understanding their activity in brain metastases is necessary for effective patient management. In this review, we discuss the biology of brain metastases in metastatic melanoma, current treatment approaches with surgery and radiotherapy, and future systemic therapeutic strategies.     

脑转移瘤神经外科、放射神经外科合作治疗的回顾分析

背景与目的：脑转移癌的治疗常需多学科合作科学处理。本研究总结神经外科、放射神经外科合作诊治脑转移瘤的经验。方法：回顾性总结神经外科和放射神经外科合作处理98例脑转移瘤的临床资料,其中,原发肿瘤为肺癌67例,乳腺癌20例,消化道恶性肿瘤5例,恶性黑色素瘤2例,原发灶不明4例;其中手术证实为腺癌3例,鳞癌1例。结果：脑转移瘤单发41例,多发57例;手术切除＋全脑放疗36例,中位生存期56周;姑息手术＋全脑放疗11例,中位生存期46周;姑息手术＋立体定向＋全脑放疗9例,中位生存期49周;立体定向＋全脑放疗42例,中位生存期52周。无手术死亡和严重并发症。结论：神经外科医生和放射治疗科医生密切合作,能提高脑转移瘤的治疗效果,减少误诊、误治。     

Treatment options for brain metastases in patients with non-small-cell lung cancer

Brain metastases are a common complication for patients with non-small-cell lung cancer and a significant cause of morbidity and mortality. In the past, treatment of brain metastases and lung cancer focused on symptom palliation with whole-brain radiotherapy (WBRT) and steroids because of the grim outlook for patients. However, recent advances in technology and surgical techniques have created more options for the management of brain metastases, which include surgery, irradiation, stereotactic radiosurgery, and chemotherapy. These aggressive approaches have resulted in an improvement of neurologic outcomes and survival rates of patients with non-small-cell lung cancer. Central nervous system (CNS) metastases can be divided into three groups: solitary CNS metastases with controlled or controllable primary disease, oligometastatic disease (fewer than 3 metastases), and multiple metastases. For patients with solitary CNS metastases, long-term survival is possible. A radical treatment approach involving surgical resection or radiosurgery, followed by WBRT, is recommended. For patients with oligometastatic disease, surgical resection or radiosurgery is considered in selected cases and WBRT is indicated. For patients with multiple metastases, WBRT is recommended. For patients with oligometastatic disease and those with multiple metastases, recent evidence indicates that systemically effective chemotherapy may produce responses and can be instituted safely before radiotherapy. The treatment timing of chemotherapy and radiotherapy should be individualized.     

Guidelines for the initial management of metastatic brain tumors: role of surgery, radiosurgery, and radiation therapy

Brain metastases are an increasingly important determinant of survival and quality of life in patients with cancer. Current approaches to the management of brain metastases are driven by prognostic factors, including the Karnofsky Performance Status, tumor histology, number of metastases, patient age, and status of systemic disease. Most brain metastases are treated with radiosurgery, computer-assisted surgery, or whole brain radiation therapy. Remarkable advances in computer-assisted neuronavigation have made neurosurgical removal of metastases safer, even in eloquent areas of the brain. Computerization also enhances the efficacy and safety of conformal radiosurgery planning using various modern stereotactic radiosurgery (SRS) technologies, including newer frameless-based systems. Controversial issues include whether to defer whole brain radiotherapy (WBRT) in patients undergoing SRS or image-guided surgery and when to use SRS "boost" in a patient undergoing WBRT. The determination of how best to apply these treatments for individual patients cannot be standardized to a single paradigm, but data from well-controlled studies help physicians make informed decisions about the benefits and risks of each approach.     

Prognostic Factors in Patients with Non-small Cell Lung Carcinoma and Brain Metastases: a Malaysian Perspective

Background: Brain metastases occur in about 20-40% of patients with non-small-cell lung carcinoma(NSCLC), and are usually associated with a poor outcome. Whole brain radiotherapy (WBRT) is widely used butincreasingly, more aggressive local treatments such as surgery or stereotactic radiosurgery (SRS) or stereotacticradiotherapy (SRT) are being employed. In our study we aimed to describe the various factors affecting outcomesin NSCLC patients receiving local therapy for brain metastases. Materials and Methods: The case records of 125patients with NSCLC and brain metastases consecutively treated with radiotherapy at two tertiary centres fromJanuary 2006 to June 2012 were analysed for patient, tumour and treatment-related prognostic factors. Patientsreceiving SRS/SRT were treated using Cyberknife. Variables were examined in univariate and multivariatetesting. Results: Overall median survival was 3.4 months (95%CI: 1.7-5.1). Median survival for patients withmultiple metastases receiving WBRT was 1.5 months, 1-3 metastases receiving WBRT was 3.6 months and 1-3metastases receiving surgery or SRS/SRT was 8.9 months. ECOG score (≤2 vs >2, p=0.001), presence of seizure(yes versus no, p=0.031), treatment modality according to number of brain metastases (1-3 metastases+surgeryor SRS/SRT±WBRT vs 1-3 metastases+WBRT only vs multiple metastases+WBRT only, p=0.007) and the use ofpost-therapy systemic treatment (yes versus no, p=0.001) emerged as significant on univariate analysis. All fourfactors remained statistically significant on multivariate analysis. Conclusions: ECOG ≤2, presence of seizures,oligometastatic disease treated with aggressive local therapy (surgery or SRS/SRT) and the use of post-therapysystemic treatment are favourable prognostic factors in NSCLC patients with brain metastases.     

Prognostic factors for melanoma in children and adolescents

BACKGROUND:

Cutaneous melanoma in childhood is rare; therefore, its prognostic factors and biologic behavior and the effectiveness of adjuvant diagnostic techniques in this group remain mostly unknown.

METHODS:

The authors conducted a retrospective, observational study on the prognostic significance of clinical and pathologic findings from 137 cutaneous and mucosal melanomas in patients aged <18 years that were reviewed by the pathology department of a large cancer center during the period from 1992 to 2006.

RESULTS:

Univariate analysis indicated that there was a significantly greater risk of metastases for patients who had previous nonmelanocytic malignancies, nodular histologic type, fusiform or spitzoid cytology, high Breslow thickness, vertical growth phase, high dermal mitotic activity, ulceration, and vascular invasion. Adjacent nevus and radial growth phase were associated with a better prognosis. Twelve patients (10.3%) died during follow‐up. Decreased overall survival was related significantly to age >10 years, previous nonmelanocytic malignancy, high Breslow thickness, high Clark level, and the presence of metastases at diagnosis. All patients who died were aged ≥11 years, and 8 of those patients had metastases at diagnosis. In multivariate analysis, higher Breslow thickness predicted an increased risk of metastases, whereas age >10 years and the presence of metastases at diagnosis were associated with decreased survival.

CONCLUSIONS:

Similar to adults, the detection of metastases at diagnosis in children with melanoma was 1 of the main factors that influenced overall survival. Melanomas that were detected in children aged <11 years appeared to have a less aggressive behavior than those detected in adults. Cancer 2010. © 2010 American Cancer Society.     

恶性胶质瘤术后放疗的疗效及预后因素分析

 目的　探讨恶性胶质瘤手术后放疗的临床疗效及预后影响因素。方法　78例恶性胶质瘤患者行手术后放疗,全脑放疗28例,局部照射34例,三维适形放疗16例。31例行术后化疗,化疗方案主要有司莫司汀、司莫司汀+替尼泊苷、替莫唑胺等。Kaplan-Meier 进行单因素分析,Cox回归多因素分析。结果　全组中位生存时间16个月,1、3、5年生存率分别是65.4 %、32.8 %、17.9 %;Ⅲ级和Ⅳ级胶质瘤中位生存时间24和11个月,1、3、5年生存率分别为72.7 %、41.5 %、22.8 %和47.8 %、10.9 %、5.4 %。单因素分析显示年龄、Karnofsky评分、病理分级、手术切除方式、手术至放疗时间各组间差异有统计学意义（P＜0.05）,多因素分析显示Karnofsky评分（P＝0.000）、病理分级（P＝0.004）和年龄（P＝0.011）是独立预后因素。结论　Karnofsky评分≥70分、病理分级为Ⅲ级和年龄<50岁的恶性胶质瘤患者预后较好,手术后放疗联合化疗可提高生存时间。     

Temozolomide With or Without Radiotherapy in Melanoma With Unresectable Brain Metastases

Summary Brain metastases are a common complication in patients suffering from metastatic malignant melanoma. We analyzed efficacy and toxicity of the alkylating agent temozolomide with excellent CNS penetration and known activity in brain metastasis in 35 patients with unresectable melanoma brain metastases. Patients received 200 mg/m² temozolomide on days 1 to 5 every 28 days as first or second-line therapy. This therapy regimen was combined with radiotherapy of the brain metastases in 22/35 patients. Grade III and IV toxicity was observed in 8/35 patients (leukopenia, granulocytopenia, thrombocytopenia, anemia, nausea and obstipation). Complete remission was observed in 1/34, partial remission in 2/34 and stable disease in 9/34 patients. In 5/34 a mixed response was assessed, 17/34 had disease progression and in one patient tumor response was not evaluable. The median progression free time was 5 (0–8) months for all patients, the median survival time for all patients from start of therapy was 8 (0–28) months, 9 (2–28) months in patients with concurrent stereotactic radiotherapy and 7 (3–17) months in patients with concurrent whole brain radiotherapy. Our results demonstrate that temozolomide can be combined with radiotherapy for the treatment of brain metastases in malignant melanoma, and that this combination may prolong survival in this patient group.     

Initial treatment of melanoma brain metastases using gamma knife radiosurgery: an evaluation of efficacy and toxicity

BACKGROUND: Melanoma is the primary malignancy that is most likely to metastasize to the brain. Because such an event carries an almost uniformly poor prognosis, the current study reviewed outcomes and identified associated prognostic indicators for 51 consecutive patients receiving gamma knife (GK) radiosurgery in the initial treatment of 188 intracranial melanoma metastases. METHODS: Data were collected retrospectively from a single-center GK radiosurgery database and from primary patient medical records and radiographs. RESULTS: At presentation, 71% of patients had multiple intracranial metastases, and extracranial metastases were present in 66% of patients. Thirty-two patients (63%) were initially treated with GK radiosurgery alone, whereas the remainder received GK radiosurgery in combination with surgery and/or whole-brain radiotherapy (WBRT). Overall median survival from time of GK radiosurgery was 26 weeks. Subgroup analysis revealed a median survival of 77 weeks for patients presenting with a single lesion, compared with 20 weeks for patients presenting with multiple lesions (P = 0.003). Patients in recursive partitioning analysis (RPA) Class I survived a median of 57 weeks, compared with a median survival of 20 weeks for patients in RPA Class II or III (P = 0.002). Although long-term imaging follow-up revealed that a majority of patients experienced distant brain metastases, multivariate analysis showed that distant metastases occurred significantly sooner in patients with extracranial metastases (P = 0.0004). Addition of initial WBRT had no significant effect on the time to development of new brain metastases (P = 0.13). Local control (crude) was observed in 81% of lesions initially treated with GK. Patients experienced improved or stable symptoms for a median of 37 weeks post-GK radiosurgery. CONCLUSIONS: Survival analyses supported the use of GK radiosurgery in the initial treatment of patients with melanoma brain metastases, with best results occurring in patients presenting with a single lesion.