Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases

PURPOSE: To report on the outcome of patients with melanoma brain metastases treated with stereotactic radiosurgery (SRS). PATIENTS AND METHODS: One hundred three patients with 153 intracranial melanoma metastases consecutively underwent Linac-based SRS between November 1991 and October 2001. The Kaplan-Meier method, univariate comparisons with log-rank test, and multivariate analyses with classification and regression tree models were performed. Calculations were based on last imaging date rather than the date of the last visit. RESULTS: Median age was 51 years (range, 18-93 years). Median Karnofsky performance status was 90. Sixty-one patients (59%) had single brain metastasis at presentation. Treatment sequence was SRS alone (61 patients), SRS + whole-brain radiotherapy (WBRT) (12 patients), and salvage SRS after WBRT (30 patients). The median tumor volume was 1.9 cm(3) (range, 0.06-22.3 cm(3)). The median SRS minimum peripheral dose and isodose was 18 Gy (range, 10-24 Gy) and 85% (range, 60%-100%), respectively. The median follow-up was 6 months for all patients and 13 months (range, 2-46 months) for patients alive at the time of analysis. The 1-year local control (LC) for all patients treated with SRS was 49%. Among the patients treated with initial SRS alone, the 1-year LC was better for patients with tumors < or =2 cm(3) than with tumors >2 cm(3): 75.2% vs. 42.3% (p < 0.05). The 1-year distant brain metastasis-free survival incidence was 14.7% for the 73 patients receiving either initial SRS alone or SRS +WBRT. The initial number of brain lesions (single vs. multiple) was the only factor with a significant effect on distant brain metastasis-free survival at 1 year: 23.5% for single metastases and 0% for multiple lesions (p < 0.05). The 1-year overall survival was 25.2%. Stratification by Score Index for Radiosurgery (SIR) revealed a significant effect on survival, which was 29% at 1 year for SIR >6 and 10% for SIR <==6 (relative hazard ratio, 2.1; p < 0.05) in classification and regression-tree multivariate analysis involving age, Karnofsky performance status, primary tumor control, tumor volume, SRS dose, SIR (>6 vs. < or =6), and systemic disease status. CONCLUSIONS: Initial SRS alone was an effective treatment modality for smaller cerebral melanoma metastases, achieving a 75% incidence of 1-year LC for < or =2 cm(3) single brain metastases and should be considered in patients with SIR >6. The role of WBRT in melanoma brain metastases cannot be addressed, owing to retrospective bias toward administering this treatment to patients with more aggressive disease. A prospective study is needed to assess the role of WBRT in patients with melanoma brain metastasis.     

The treatment of brain metastases from malignant melanoma

Metastasis to the CNS develops in nearly half of patients with advanced melanoma; in 15% to 20% of these patients, the CNS is the first site of relapse. While systemic therapy for metastatic melanoma produces objective responses in 15% to 50% of patients, the available drugs do not penetrate well into the CNS, and these patients rarely benefit from systemic therapy. Although brain metastasis may be treated with surgery and/or stereotactic radiosurgery (SRS) when disease is limited to approximately one to three lesions, treatment for patients with large or multiple metastases is limited to whole brain irradiation (WBRT). While formal response and survival analyses of the impact of WBRT in melanoma have not been reported, the estimated median survival time for unselected patients with CNS metastases is only 2 to 4 months, with 1-year survival rates of less than 13%. In a selected population of patients with limited CNS involvement, surgical resection alone or in combination with WBRT appears to prolong median survival. More recently, SRS has been shown to be an effective local treatment for selected patients with brain metastases. In several retrospective reports of patients with melanoma CNS metastases, treatment with surgical resection alone or in combination with WBRT has been demonstrated to prolong median survival. More recently, SRS has been shown to be an effective local treatment for selected patients with brain metastases. In several retrospective reports, patients with CNS metastases from melanoma treated with a combination of WBRT plus SRS or SRS alone had median survivals and rates of control in the CNS superior to published reports for traditional WBRT. Most of these patients died from progressive extracranial disease with locally controlled CNS disease. Investigation of the contribution of newer systemic agents to the control of melanoma metastatic to the CNS has been based on the identification of drugs that have antitumor activity and the ability to cross the blood-brain barrier. Fotemustine is a nitrosourea that produced similar activity in CNS metastasis as in systemic disease, with a response rate of about 25%. Temozolomide (TMZ) is an oral alkylating agent that acts via the same mechanism as dacarbazine (DTIC), the most active single agent in melanoma. TMZ, which is highly active in brain tumors, has also been associated with activity in systemic and CNS metastases in melanoma patients, also in the 25% range. Efforts are underway to assess the additive benefit of TMZ and other drugs to WBRT or focused radiotherapy in this disease.     

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.     

Prospective study of stereotactic radiosurgery without whole brain radiotherapy in patients with four or less brain metastases: incidence of intracranial progression and salvage radiotherapy

This prospective study was conducted to evaluate the treatment outcome after stereotactic radiosurgery (SRS) alone with special attention to its influence on intracranial freedom from progression (FFP), local control, time to whole brain radiotherapy (WBRT), and survival. Forty-one patients with brain metastases who met the inclusion criteria were enrolled in this prospective cohort and treated by SRS alone between January 1998 and September 2001. The overall local control rate was 76%. The one year actuarial intracranial FFP was 33%. Ten patients (24%) had relapse at treated site. Twenty-three patients (56%) had intracranial progression with a median time of 4.25 months (1–24.6). Salvage radiotherapy was given in 21 patients (51%). Only 12 (29%) patients required WBRT with the median time to WBRT after SRS of 4.85 months. Nine patients (22%) underwent additional SRS at the median time of 5 months after the first procedure. The median survival was 10 months. At the time of follow up, 16 patients (39%) were still alive with a range of 6–31 months. This prospective study suggests that the omission of WBRT in the initial treatment of patients with SRS for four or less brain metastases may allow up to 70% of patients to avoid WBRT.     

Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases

PURPOSE: To evaluate the usefulness of whole brain radiotherapy (WBRT) and of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) for brain metastases among patients receiving stereotactic radiosurgery (SRS). METHODS AND MATERIALS: A retrospective analysis was performed on 135 patients who underwent linear accelerator (Linac) (n = 73) or Gamma Knife (n = 62) SRS for newly diagnosed brain metastases at the Cleveland Clinic Foundation between 8/89 and 12/98. Univariate and multivariate analyses were performed to evaluate the effects of age, primary site, control of the primary, interval to development of brain metastases (disease-free interval [DFI]), number of brain metastases, presence of extracranial metastases, Karnofsky performance status (KPS), treatment of brain metastases, and RPA class on overall survival. RESULTS: Application of the RPA classification revealed 29 patients fit the criteria for class I, 96 for class II, and 10 for class III. All of the patients underwent SRS. Fifty-seven patients also received WBRT at the time of initial presentation (SRS and immediate WBRT), and 78 patients received WBRT only if CNS relapse occurred (SRS alone). The median survival for all patients was 7.9 months (range: 1.1-90.1), and was 11.2 months for RPA class I compared to 6. 9 months for RPA classes II-III (p = 0.016). Median survival was 10. 5 months following SRS alone compared to 6.4 months following SRS and WBRT (p = 0.07). On univariate analysis, KPS >/= 80% (p = 0.002) and absence of systemic disease (p = 0.013) were also associated with longer survival, whereas control of the primary, DFI, and number of brain metastases did not have an impact. Multivariate analysis revealed only RPA class (p = 0.023) to be an independent predictor for overall survival, whereas treatment group (p = 0.079) was only marginally significant. At 2 years, immediate WBRT improved control at the original site of metastases (80% vs. 52%, p = 0.03) and prevention of new metastatic sites within the brain, 74% vs. 48% (p = 0.06). The 2-year intracranial disease-free survival was 60% following SRS and WBRT compared to only 34% following SRS alone (p = 0.03). CONCLUSIONS: Despite the inherent biases to select more favorable patients for SRS, the RPA class retains its prognostic value. Omission of WBRT from the initial management was not detrimental in terms of overall survival; however, progressive disease occurred in over 50% of patients treated in this manner. Further studies are required to determine which, if any, patients should be considered for SRS with WBRT held in reserve.     

立体定向放射治疗肺癌脑转移疗效分析

目的探讨不同放射治疗方法对肺癌脑转移的疗效.方法176例由病理学证实的肺癌脑转移患者分为4组:单纯全脑放疗(WBRT)组、全脑放疗加立体定向放射外科(WBRT SRS)组、单纯立体定向放射治疗(SRT)组、全脑放疗加立体定向放射治疗(WBRT SRT)组.SRS治疗单次靶区平均周边剂量8～20Gy,总剂量20～32Gy;SRT治疗单次靶区平均周边剂量2～5Gy,总剂量25～60Gy;WBRT1.8～2Gy/次,总剂量30～40Gy.结果四组的局部控制率分别为47.0%、87.7%、86.5%和78.0%;中位生存期分别为5.0,11.0,11.5和10.0个月;局部无进展生存期分别为3.33,8.33,9.33和7.67个月;颅脑无新病灶生存期分别为4.11,8.57,9.03和6.12个月.在死因分析中,WBRT组死于脑转移的比率为57.6%,较其他三组高.而WBRT SRS组的晚期放射反应的发生率为12.2%,较其他组高.结论肺癌单发脑转移瘤患者的最佳治疗方式是单纯立体定向放射治疗,治疗失败后再行挽救性全脑照射或立体定向放疗.对于多发脑转移,全脑放疗加立体定向放射治疗(WBRT SRT)在提高生存率以及减少并发症方面优于其他治疗方法.     

伽玛刀治疗肺癌脑转移瘤生存与预后分析

目的:分析伽玛刀治疗肺癌脑转移瘤患者的生存及预后影响因素。方法:回顾性分析行伽玛刀治疗的56例肺癌脑转移瘤患者,单纯SRS组22例,单纯SRT组16例,联合全脑放疗(WBRT)组9例,行伽玛刀挽救组7例,行联合WBRT挽救组2例。Log rank法单因素分析影响预后的因素。结果:全组经治疗后6月、1年生存率分别为50%、10%,中位生存期为6个月。单纯SRS、单纯SRT、SRS联合WBRT、SRS/SRT挽救组、SRS+WBRT挽救组6月生存率分别为59%、55%、40%、33%、0%,中位生存期分别为8、9、6、5、3个月（P=0.005）。其中,SRS对SRT（P=0.157）、SRS对SRS+WBRT（P=0.551）、SRT对SRS+WBRT（P=0.266）、SRS/SRT挽救组对SRS+WBRT挽救组（P=0.177）无统计学意义。单因素分析显示影响总生存率的因素有原发灶的控制情况、病理、中枢外转移情况、KPS评分、RPA分级、病灶所处位置、前期化疗、前期颅内治疗、病灶数目(P=0.000、0.013、0.002、0.000、0.000、0.000、0.043、0.011、0.037)。多因素分析显示KPS评分、原发灶控制、病理、前期颅内处理影响生存（P=0.000、0.005、0.006、0.002）。结论:用伽玛刀行单次SRS或分次SRT或与WBRT联合治疗在对生存获益上相似;KPS评分、原发灶控制情况、病理类型、前期颅内处理是影响生存的主要因素。     

Multidisciplinary treatment of brain metastases derived from clear cell renal cancer incorporating stereotactic radiosurgery

BACKGROUND

Brain metastases are a frequent complication in patients with metastatic clear cell renal cancer. Survival after whole‐brain radiotherapy (WBRT) is disappointing. A retrospective analysis of multimodality treatment was performed in patients who had received linear accelerator (LINAC)‐based stereotactic radiosurgery (SRS).

METHODS

Thirty‐two patients underwent SRS‐based treatment for 71 metastatic foci between 2000 and 2006. All patients had a Karnofsky performance status ≥70 and all 32 patients had extracranial metastatic disease (Radiation Therapy Oncology Group recursive partitioning analysis [RPA] Class 2). Survival was calculated from the time of diagnosis of brain metastases. The minimum potential follow‐up was 1 year after SRS. Univariate and multivariate analysis of potential prognostic factors affecting survival was performed.

RESULTS

Twenty‐six patients required only 1 SRS treatment (84%) to achieve central nervous system (CNS) control, whereas 5 patients received 2 to 3 treatments (16%). The median survival of renal cancer patients from the diagnosis of brain metastases was 10.1 months (95% confidence interval, 6.4‐14.8 months). One‐year and 3‐year survival rates were 43% and 16%, respectively. The addition of surgery or WBRT did not appear to prolong survival. Immunotherapy after control of brain metastases with SRS appeared to result in significantly improved survival. Survival was also found to be strongly influenced by prognostic stratification of metastatic disease using Motzer or modified risk criteria.

CONCLUSIONS

The results of the current study demonstrated that SRS‐based treatment of patients with up to 5 brain metastases from clear cell renal cancer is feasible and results in excellent CNS control. Survival beyond 3 years from the time of diagnosis of brain metastases was achievable in 16% of patients and was associated with the use of systemic immunotherapy with interleukin‐2 and interferon but not antiangiogenic agents. Cancer 2008. © 2008 American Cancer Society.     

Initial clinical experience with frameless radiosurgery for patients with intracranial metastases

PURPOSE: To review the initial clinical experience with frameless stereotactic radiosurgery (SRS) for treating intracranial metastatic disease. METHODS AND MATERIALS: Sixty-four patients received frameless SRS for intracranial metastatic disease. Minimum follow-up was 6 months with none lost to follow-up. Patients had a median of 2 metastases and a maximum of 4. The median number of isocenters was 2 with median arcs of 10 and median dose of 17.5 Gy. Thirteen patients were treated for progressive/recurrent disease after surgical resection or whole brain radiotherapy (WBRT). Fifty-one patients were treated with frameless SRS as an an adjunct to initial treatment. Of the total treated, 17 were treated with SRS alone, 20 were treated with WBRT plus SRS, 16 were treated with surgical resection plus SRS, and the remaining 11 were treated with surgical resection plus WBRT plus SRS. RESULTS: With a median actuarial follow-up period of 8.2 months, ultimate local control was 88%. The median time to progression was 8.1 months. The median overall survival was 8.7 months. Of the 17 patients treated with SRS alone, 86% had ultimate local control with mean overall survival of 7.1 months. Of the 13 patients who received surgical resection plus SRS without WBRT as primary treatment, there was 85% ultimate local control with an overall survival of 10.3 months. Three patients treated with initial surgery alone had recurrence treated with SRS 2-3 months after resection. All these patients obtained local control and median survival was >10 months. Of the 13 patients who received WBRT followed by SRS as boost treatment, 92% had local control and mean overall survival was 7.3 months. Of 7 patients who received SRS after recurrence after WBRT, 100% had local control with median survival of 8.2 months. For 8 patients who received surgery followed by WBRT and SRS, local control was 50%; however, ultimate intracranial control was achieved in 7 of 8 patients with repeat SRS and surgical resection. The overall survival in this group of patients was 14.7 months. No patient had a serious (Grade 3 or higher) complication requiring intervention. CONCLUSIONS: Frameless optically guided radiosurgery is less invasive, can be performed as a standard radiotherapy-based simulation procedure, and maintains submillimetric accuracy. Our initial results with frameless SRS for metastatic disease suggest survival times and local control (88%) eqiuvalent to frame-based methodologies. Practical noninvasive delivery makes treatment and potential retreatment to avoid WBRT more feasible.     

Linear accelerator based stereotactic radiosurgery for melanoma brain metastases

Purpose: Melanoma is one of the most common malignancies to metastasize to the brain. Many patients with this disease will succumb to central nervous system (CNS) disease, highlighting the importance of effective local treatment of brain metastases for both palliation and survival of the disease. Our objective was to evaluate the outcomes associated with stereotactic radiosurgery (SRS) in the treatment of melanoma brain metastases. Materials and Methods: We retrospectively reviewed 54 patients with a total of 103 tumors treated with SRS. Twenty patients had prior surgical resection and nine patients underwent prior whole brain radiation therapy (WBRT). 71% of patients had active extracranial disease at the time of SRS. Median number of tumors treated with SRS was 1(range: 1-6) with median radiosurgery tumor volume 2.1 cm 3 (range: 0.05-59.7 cm 3 ). The median dose delivered to the 80% isodose line was 24 Gy in a single fraction. Results: The median follow-up from SRS was five months (range:1-30 months). Sixty-five percent of patients had a follow-up MRI available for review. Actuarial local control at six months and 12 months was 87 and 68%, respectively. Eighty-one percent of patients developed new distant brain metastases at a median time of two months. The six-month and 12-month actuarial overall survival rates were 50 and 25%, respectively. The only significant predictor of overall survival was surgical resection prior to SRS. Post-SRS bleeding occurred in 18% of patients and at a median interval of 1.5 months. There was only one episode of radiation necrosis with no other treatment-related toxicity. Conclusion: SRS for brain metastases from melanoma is safe and achieves acceptable local control.     

Radiation Therapy for Melanoma Brain Metastases: A Systematic Review

BackgroundRadiation therapy (RT) for melanoma brain metastases, delivered either as whole brain radiation therapy (WBRT) or as stereotactic radiosurgery (SRS), is an established component of treatment for this condition. However, evidence allowing comparison of the outcomes, advantages and disadvantages of the two RT modalities is scant, with very few randomised controlled trials having been conducted. This has led to considerable uncertainty and inconsistent guideline recommendations. The present systematic review identified 112 studies reporting outcomes for patients with melanoma brain metastases treated with RT. Three were randomised controlled trials but only one was of sufficient size to be considered informative. Most of the evidence was from non-randomised studies, either specific treatment series or disease cohorts. Criteria for determining treatment choice were reported in only 32 studies and the quality of these studies was variable. From the time of diagnosis of brain metastasis, the median survival after WBRT alone was 3.5 months (IQR 2.4–4.0 months) and for SRS alone it was 7.5 months (IQR 6.7–9.0 months). Overall patient survival increased over time (pre-1989 to 2015) but this was not apparent within specific treatment groups.ConclusionsThese survival estimates provide a baseline for determining the incremental benefits of recently introduced systemic treatments using targeted therapy or immunotherapy for melanoma brain metastases.Key words: radiation therapy, stereotactic radiosurgery, melanoma, brain metastases     

Stereotactic radiosurgery alone versus resection plus whole-brain radiotherapy for 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients

BACKGROUND: The objective of this study was to compare stereotactic radiosurgery (SRS) alone with resection plus whole-brain radiotherapy (WBRT) for the treatment of patients in recursive partitioning analysis (RPA) class 1 and 2 who had 1 or 2 brain metastases. METHODS: Two hundred six patients in RPA class 1 and 2 who had 1 or 2 brain metastases were analyzed retrospectively. Patients in Group A (n = 94) received from 18 grays (Gy) to 25 Gy SRS, and patients in Group B (n = 112) underwent resection of their metastases and received 10 x 3 Gy/20 x 2 Gy WBRT. Eight other potential prognostic factors were evaluated regarding overall survival (OS), brain control (BC), and local control (LC) of treated metastases: age, sex, performance status, tumor type, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to treatment of brain metastases. RESULTS: A comparison of the 2 treatment groups did not reveal significantly different OS (P = .19), BC (P = .52), or LC (P = .25). In RPA subgroup analyses, outcome also did not differ significantly for either RPA class of patients (P values from .21 to .83). On multivariate analysis, improved OS was associated with age < or =60 years (relative risk [RR], 1.75; P = .002), better performance status (RR, 1.67; P = .015), no extracranial metastases (RR, 2.84; P < .001), interval from tumor diagnosis to treatment >12 months (RR, 1.70; P = .003), and RPA class 1 (RR, 1.51; P = .016). Improved BC was associated with a single metastasis (RR, 1.54; P = .034) and an interval from tumor diagnosis to treatment >12 months (RR, 1.58; P = .019), and improved LC was associated with an interval from tumor diagnosis to treatment >12 months (RR, 1.59; P = .047). CONCLUSIONS: SRS alone appeared to be as effective as resection plus WBRT in the treatment of 1 or 2 brain metastases for patients in RPA class 1 and 2. Patient outcomes were associated with age, Karnofsky performance status, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to treatment.     

Radiation therapy for brain metastases from breast cancer

BACKGROUND: Breast cancer is one of the most common malignancies that metastasize to the brain. Radiation therapy plays a central role in the management of brain metastases. METHODS: The medical records of 36 patients with brain metastases from breast cancer who underwent whole-brain radiation therapy (WBRT) at Kyoto University Hospital between 1993 and 2001 were reviewed. The treatment outcomes were analyzed retrospectively. RESULTS: The median age at the time of diagnosis of brain metastases was 52 years. Only 4 patients (11%) had a single metastasis, while the others had multiple metastases. Uncontrolled extracranial metastases were present in 26 patients at the time of diagnosis of brain metastases. All patients received WBRT at a median dose of 31 Gy. Eight patients received conventional external-beam boost irradiation, and 2 received boost stereotactic radiosurgery (SRS). The overall median survival time was 7.9 months. Uncontrolled extracranial metastases except for bone metastases and old age were significantly associated with a poor survival rate. Twenty-six patients (82%) showed initial response, but 15 developed CNS failure, including 9 patients whose tumor recurred at the original site, 4 patients who developed tumors elsewhere in the brain and 3 patients who exhibited meningeal spread. The median duration of intracranial failure was 5.0 months. Whole-brain dose, and total tumor dose did not affect intracranial control. CONCLUSIONS: Radiation therapy yielded a high initial response, but the duration of effect was limited with external beam irradiation alone. New treatment strategies such as adding SRS need to be studied further.     

Population-based outcomes of boost versus salvage radiosurgery for brain metastases after whole brain radiotherapy

Purpose

We conducted a retrospective population-based study to examine the survival outcomes in patients with brain metastases treated with salvage stereotactic radiosurgery (SRS), compared to boost SRS, after previous whole brain radiotherapy (WBRT).

Methods and materials

From January 2000 to June 2011, 191 patients treated with WBRT and SRS for brain metastases in British Columbia were studied. Patients were divided into a boost cohort and a salvage cohort. The criteria used to determine eligibility for SRS were: 1–3 metastases, ?4 cm size, Karnofsky performance status ?70, and control of extracranial disease.

Results

Diagnosis by primary site was 84 lung, 47 breast, 15 melanoma, 12 renal, 9 colorectal, and 24 other. There were 113 patients (59%) in the boost cohort and 78 patients (41%) in the salvage cohort. The median overall survival from WBRT for the whole population was 17.7 months: 12.1 months for the boost cohort and 22.7 months for the salvage cohort. There was no difference in median survival after SRS for the boost and salvage cohorts (11.2 vs. 11.2 months, p = 0.78).

Conclusions

In selected patients with brain metastases treated with WBRT, survival following salvage SRS is as good as survival after WBRT + boost SRS.     

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.     

Strategy of surgery and radiation therapy for brain metastases

Cancer patients with brain metastases have poor prognoses and their median survival time is about 1 year. Surgery with whole-brain radiation therapy (WBRT) has been used in the treatment of single brain metastasis measuring 3 cm or more. Stereotactic radiosurgery (SRS) including the use of the Gamma knife and Cyberknife is widely used for the treatment of small and multiple brain metastases; however, recent clinical studies have revealed that SRS + WBRT is superior to WBRT or SRS alone in terms of survival time and local tumor control rates. Here, surgical indications and the strategy of surgery and radiation therapy are discussed, based on many clinical trials of treatments for brain metastases. To improve the survival rate and quality of life for these cancer patients with brain metastases, it is necessary to choose the most suitable mode of surgery and radiotherapy with the close cooperation of physicians, surgeons, radiologists, and neurosurgeons, based on accumulated evidence.     

Dose-response relationships for radiotherapy of brain metastases: role of intermediate-dose stereotactic radiosurgery plus whole-brain radiotherapy

The effects of intermediate-dose radiotherapy consisting of whole-brain radiotherapy (WBRT, 10 fractions of 3 Gy) plus stereotactic radiosurgery (SRS) were studied prospectively. Twenty-five adult patients with 31 brain metastases received WBRT plus linear accelerator (LINAC)-based single dose SRS with fixed treatment parameters (10 Gy at the isocenter, target volume enclosed by the 90% isodose). Median age was 63 years, median Karnofsky performance status 80%, and median diameter of brain metastases 2.4 cm. Fifteen patients had non-small-cell lung cancer. Because of some early deaths, only 26 lesions could be evaluated for response. We observed 1 complete and 15 partial remissions. Median time to progression inside or outside the SRS volume was 4.5 months. Actuarial local control of SRS-treated lesions was 61% at 1 year. At that time, only 37% of patients were free from new lesions outside the SRS volume. Median survival and cause-specific survival were 2.3 and 4.5 months, respectively (1-year survival rate 8% and 21%). Ten patients died of progressive brain metastases, 13 from extracranial disease progression (unknown cause of death in 2 cases). Comparable to SRS studies with higher doses, the majority of brain failures occurred outside the SRS volume and more patients died of extracranial progression than of uncontrolled brain metastases. Failure to improve survival can be explained by the high percentage of patients with extracranial metastases (52%). However, the present results appear less favorable than those of previous studies of SRS with 15 Gy to 16 Gy (1-year actuarial local control rates of 66-89%). Therefore, we recommend SRS with 15 Gy to 16 Gy for patients whose favorable prognostic factors justify a boost after WBRT.     

Whole Brain Radiotherapy Combined with Stereotactic Radiosurgery versus Stereotactic Radiosurgery Alone for Brain Metastases

Background: The aim of this study was to evaluate the effect of whole brain radiotherapy (WBRT) combined with streotactic radiosurgery versus stereotactic radiosurgery (SRS) alone for patients with brain metastases. Materials and Methods: This was a retrospective study that evaluated the results of 46 patients treated for brain metastases at Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiation Oncology Department, between January 2012 and January 2015. Twenty-four patients were treated with WBRT+SRS while 22 patients were treated with only SRS. Results: Time to local recurrence was 9.7 months in the WBRT+SRS arm and 8.3 months in SRS arm, the difference not being statistically significant (p= 0.7). Local recurrence rate was higher in the SRS alone arm but again without significance (p=0,06). Conclusions: In selected patient group with limited number (one to four) of brain metastases SRS alone can be considered as a treatment option and WBRT may be omitted in the initial treatment.     

Salvage stereotactic radiosurgery effectively treats recurrences from whole-brain radiation therapy

BACKGROUND.

The purpose of the current study was to examine overall survival (OS) and time to local failure (LF) in patients who received salvage stereotactic radiosurgery (SRS) for recurrent brain metastases (BM) after initial management that included whole‐brain radiation therapy (WBRT).

METHODS.

The records of 1789 BM patients from August 1989 to November 2004 were reviewed. Of these, 111 underwent WBRT as part of their initial management and SRS as salvage. Patients were stratified by Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, primary disease, dimension of the largest metastases and number of BM at initial diagnosis, and time to first brain recurrence after WBRT. Overall survival, survival after SRS, and time to local and distant failure were analyzed.

RESULTS.

The median OS from the initial diagnosis of BM was 17.7 months. Median survival after salvage SRS for the entire cohort was 9.9 months. Median survival after salvage SRS was 12.3 months in patients who had their first recurrence >6 months after WBRT versus 6.8 months for those who developed disease recurrence ≤6 months after (P = .0061). Primary tumor site did not appear to affect survival after SRS. Twenty‐eight patients (25%) developed local recurrence after their first SRS with a median time of 5.2 months. A dose <22 grays and lesion size >2 cm were found to be predictive of local failure.

CONCLUSIONS.

In this study, patients who recurred after WBRT and were treated with salvage SRS were found to have good local control and survival after SRS. WBRT provided good initial control, as 45% of these patients failed >6 months after WBRT. Those with a longer time to failure after WBRT had significantly longer survival after SRS. Cancer 2008. © 2008 American Cancer Society.     

多发脑转移瘤放疗方式与预后

 目的 探讨多发脑转移瘤放疗方式与预后的关系。方法 112例多发脑转移瘤患者分别采用全脑照射、立体定向放射治疗以及全脑照射结合立体定向放射治疗，分析不同放疗方法的生存期及脑转移致死率。结果 全脑照射、立体定向放射治疗以及全脑照射结合立体定向放射治疗组的中位生存期分别为3．8、7．8及8．0个月。脑转移致死率全脑照射组67．7％，立体定向放射治疗组15．7％，全脑照射结合立体定向放射治疗组11．6％。结论 立体定向放射治疗可使脑转移灶较少的患者局控率提高，生存期延长。