Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases: an update

Brain metastases are unfortunately a common occurrence in patients with cancer. Whole-brain radiation therapy (WBRT) is still considered the standard of care in the treatment of brain metastases. Stereotactic radiosurgery (SRS) offers the additional ability to treat tumors with relative sparing of normal brain tissue in a single fraction. While the addition of SRS to WBRT has been shown to improve survival and local tumor control in selected patients, the idea of deferring WBRT in order to avoid its effects on normal tissues and using SRS alone continues to generate significant discussion and interest. Three recent randomized trials from Japan, Europe and the MD Anderson Cancer Center (TX, USA) have attempted to address this issue. In this article, we update a previous review by discussing these trials to compare the outcomes for SRS alone versus SRS plus WBRT for limited metastases. We also discuss recent nonrandomized evidence for the use of SRS alone for oligometastatic disease.     

SRS、WBRT 及 WBRT ＋SRS 治疗1～4个脑转移瘤的 Meta 分析

目的：探讨立体定向放射外科（SRS）、全脑放疗（WBRT）及全脑放疗联合立体定向治疗1～4个脑转移瘤,并为进一步研究提供循证医学依据。方法：根据设定的纳入、排除标准,在 PubMed、Springer －link、Cancer list 数据库、中国生物医学文献数据库（CBM）、万方数据库、CNKI 知识网络服务平台及其他期刊进行相关随机对照试验检索。单变量计数资料的效应量用优势比（OR）和95％可信区间（95％CI）表示,用 Rev-man 5．2软件对数据进行异质性检验后采用固定效应模型或随机效应模型对数据进行分析。结果：共检索出1985－2014年间发表的126篇相关文献,最终得到8篇包含1213例脑转移瘤患者的随机对照试验符合所纳入的标准。SRS 与 WBRT ＋SRS 比较：WBRT ＋SRS 虽能提高脑转移瘤1年局部控制率及远处肿瘤控制率（OR ＝0．43,95％CI：0．29～0．63,P ＜0．0001;OR ＝0．42,95％CI：0．30～0．57,P ＜0．00001）;但不能提高1年生存率且不良反应及神经认知异常发生率高（OR ＝1．27,95％CI：0．93～1．73,P ＝0．14;OR ＝0．50,95％CI：0．28～0．89,P ＝0．02;OR ＝0．41,95％CI：0．21～0．78,P ＝0．006）。SRS 与 WBRT 比较：SRS 治疗脑转移瘤可明显提高患者1年生存率及1年局部肿瘤控制率,但远处肿瘤控制率与WBRT相当（OR＝2．78,95％CI：1．57～4．92,P ＝0．0004;OR ＝4．8,95％CI：2．69～8．57,P ＜0．00001;OR ＝0．52,95％CI：0．15～1．83,P ＝0．31）。WBRT ＋SRS 与单独 WRBT 比较：1年局部肿瘤控制率及1年生存率无明显差别（OR ＝1．23,95％CI：0．81～1．86,P ＝0．32;OR ＝1．21,95％CI：0．76～1．93,P ＝0．42）。结论：1～4个脑转移瘤患者,单独 SRS 是理想治疗方法。     

A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy, or both for patients presenting with a limited number of brain metastases

BACKGROUND:

To perform a meta‐analysis on newly diagnosed brain metastases patients treated with whole‐brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) boost versus WBRT alone, or in patients treated with SRS alone versus WBRT and SRS boost.

METHODS:

The meta‐analysis primary outcomes were overall survival (OS), local control (LC), and distant brain control (DBC). Secondary outcomes were neurocognition, quality of life (QOL), and toxicity. Using published Kaplan‐Meier curves, results were pooled using hazard ratios (HR).

RESULTS:

Two RCTs reported on WBRT and SRS boost versus WBRT alone. For multiple brain metastases (2‐4 tumors) we conclude no difference in OS, and LC significantly favored WBRT plus SRS boost. Three RCTs reported on SRS alone versus WBRT plus SRS boost (1‐4 tumors). There was no difference in OS despite both LC and DBC significantly favoring WBRT plus SRS boost. Although secondary endpoints could not be pooled for meta‐analysis, those RCTs evaluating SRS alone conclude better neurocognition using the validated Hopkins Verbal Learning Test, no adverse risk in deteriorating Mini‐Mental Status Exam scores or in maintaining performance status, and fewer late toxicities. We conclude insufficient data for QOL outcomes.

CONCLUSIONS:

For selected patients, we conclude no OS benefit for WBRT plus SRS boost compared with SRS alone. Although additional WBRT improves DBC and LC, SRS alone should be considered a routine treatment option due to favorable neurocognitive outcomes, less risk of late side effects, and does not adversely affect the patients performance status. Cancer 2012. © 2011 American Cancer Society.     

X线立体定向放射治疗脑转移瘤的疗效分析

目的观察立体定向放射手术治疗脑转移瘤的疗效。方法X线立体定向放射治疗脑转移瘤患者47例,采用10MV的直线加速器多个非共面弧旋转照射,肿瘤剂量为18～25Gy(平均22.1Gy)。40例患者在术后接受了肿瘤剂量30～40Gy的全脑放疗。结果中位生存期为11个月,1年生存率37.5%,疗后3个月的肿瘤控制率为90.7%,KPS≥70、原发肿瘤已控和无颅外转移患者的预后较好(P<0.05)。结论立体定向放射治疗脑转移瘤是安全和有效的。     

Whole-brain radiotherapy versus stereotactic radiosurgery for patients in recursive partitioning analysis classes 1 and 2 with 1 to 3 brain metastases

BACKGROUND: The authors investigated whether stereotactic radiosurgery (SRS) alone improved outcomes for patients in recursive partitioning analysis (RPA) Classes 1 and 2 who had 1 to 3 brain metastases compared with whole-brain radiotherapy (WBRT). METHODS: Data regarding 186 patients in RPA Classes 1 and 2 who had 1 to 3 brain metastases and who received either 30 to 40 grays (Gy) of WBRT (n = 91 patients) or 18 to 25 Gy SRS (n = 95 patients) were analyzed retrospectively. Eight other potential prognostic factors were evaluated regarding overall survival (OS), entire brain control (BC), local control (LC) of treated metastases, and brain control distant from treated metastases (distant control [DC]): Those 8 factors were age, sex, performance status, tumor type, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to radiotherapy. RESULTS: On multivariate analysis of OS, age ( risk ratio [RR], 1.51; P = .024), Karnofsky performance status (KPS) (RR, 1.98; P = .002), and extracranial metastases (RR, 2.26; P < .001) were significant, whereas the radiation regimen was not significant (P = .89). On multivariate analysis of BC, only the radiation regimen (RR, 1.33; P = .003) was found to be significant. On multivariate analysis of LC, radiation regimen (RR, 1.63; P < .001) and sex (RR, 1.62; P = .022) were significant. On multivariate analysis of DC, KPS (RR, 1.85; P = .049) and extracranial metastases (RR, 1.69; P = .047) were significant. The radiation regimen was not found to be significant even on univariate analysis (P = .80). In RPA class subgroup analyses, BC and LC were better after SRS than WBRT for patients in RPA Classes 1 and 2, whereas OS and DC did not differ significantly. CONCLUSIONS: For patients in RPA Classes 1 and 2 who had 1 to 3 brain metastases, SRS alone was associated with improved BC and LC compared with 30 to 40 Gy WBRT, whereas OS and DC were not significantly different. Similar results were observed in separate subgroup analyses of patients in RPA Class 1 and RPA Class 2.     

A nomogram for predicting distant brain failure in patients treated with gamma knife stereotactic radiosurgery without whole brain radiotherapy

Background

We review our single institution experience to determine predictive factors for early and delayed distant brain failure (DBF) after radiosurgery without whole brain radiotherapy (WBRT) for brain metastases.

Materials and methods

Between January 2000 and December 2010, a total of 464 patients were treated with Gamma Knife stereotactic radiosurgery (SRS) without WBRT for primary management of newly diagnosed brain metastases. Histology, systemic disease, RPA class, and number of metastases were evaluated as possible predictors of DBF rate. DBF rates were determined by serial MRI. Kaplan–Meier method was used to estimate rate of DBF. Multivariate analysis was performed using Cox Proportional Hazard regression.

Results

Median number of lesions treated was 1 (range 1–13). Median time to DBF was 4.9 months. Twenty-seven percent of patients ultimately required WBRT with median time to WBRT of 5.6 months. Progressive systemic disease (χ²= 16.748, P < .001), number of metastases at SRS (χ² = 27.216, P < .001), discovery of new metastases at time of SRS (χ² = 9.197, P < .01), and histology (χ² = 12.819, P < .07) were factors that predicted for earlier time to distant failure. High risk histologic subtypes (melanoma, her2 negative breast, χ² = 11.020, P < .001) and low risk subtypes (her2 + breast, χ² = 11.343, P < .001) were identified. Progressive systemic disease (χ² = 9.549, P < .01), number of brain metastases (χ² = 16.953, P < .001), minimum SRS dose (χ² = 21.609, P < .001), and widespread metastatic disease (χ² = 29.396, P < .001) were predictive of shorter time to WBRT.

Conclusion

Systemic disease, number of metastases, and histology are factors that predict distant failure rate after primary radiosurgical management of brain metastases.     

颅内转移瘤放射治疗方案的优化

目的:探讨颅内转移瘤放射治疗的优化方案。方法:回顾性分析2005年7月-2008年7月收治的50例颅内转移瘤患者。原发灶均得到控制,30例采用全脑放疗+立体定向放射外科(联合组),20例采用单纯立体定向放射外科(单一组)。立体定向放射外科处方剂量均采用45%-75%等剂量线包绕计划靶区,边缘剂量15-20Gy,中心剂量30-45Gy,一次完成。全脑放疗每次分割剂量为2Gy,1次/d,5次/w,总剂量40Gy/4w。结果:联合组的有效率明显高于单一组(P<0.05)。两组1年、2年生存率比较无差异(P>0.05)。两组均无生存3年以上患者。按病灶数进行分层研究:1年生存率单发病灶两组差异无显著性(P=0.212),1年生存率多发病灶联合组明显优于单一组(P=0.001),2年生存率两组差异无显著性。结论:对于多发颅内转移瘤患者,全脑放疗联合立体定向放射外科是比较优化的选择方案,而对于单发的颅内转移瘤患者,则可以先全脑放疗加立体定向放射外科或者直接立体定向放射外科治疗。     

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.     

Hypofractionated stereotactic radiotherapy in combination with whole brain radiotherapy for brain metastases

BACKGROUND: The efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) in combination with whole brain radiotherapy (WBRT), for the treatment of 1-4 brain metastases, using a non invasive fixation of the skull, was investigated. METHODS: Between 04/2001 and 01/2006 30 patients with 44 brain metastases underwent irradiation. Every patient received WBRT (10 x 3 Gy); 41/44 lesions received HSRT boost with a median dose fraction of 6 Gy, the fractionation schemes were 3 x 6 Gy and 4 x 8 Gy; a median total dose of 18 Gy was delivered to the tumor isocenter. RESULTS: The median survival period was 9.15 months, the actuarial 1-year overall survival and freedom from new brain metastases were 36.6% and 87.9%, respectively; at univariate analysis Karnofsky Performance Status (KPS) was statistically significant (P = 0.05); the actuarial 1-year local control for the 41/44 lesions was 86.1%. No patient had acute or late complications. CONCLUSIONS: HSRT as a concomitant boost during WBRT is a safe and well tolerated treatment for selected patients with brain metastases.     

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。     

Hypofractionated stereotactic radiotherapy for the treatment of brain metastases

BACKGROUND:

This retrospective review evaluated the efficacy and toxicity profiles of various dose fractionations using hypofractionated stereotactic radiotherapy (HSRT) in the treatment of brain metastases.

METHODS:

Between 2004 and 2007, 36 patients with 66 brain metastases were treated with HSRT. Nine of these subjects were excluded because of the absence of post‐treatment magnetic resonance imaging scans, resulting in 27 patients with a total of 52 lesions. Of these 52 lesions, 45 lesions were treated with whole‐brain radiotherapy plus a HSRT boost and 7 lesions were treated with HSRT as the primary treatment. The median prescribed dose was 25 grays (Gy) (range, 20 Gy‐36 Gy) with a median of 5 fractions (range, 4 fractions‐6 fractions) to a median 85% isodose line (range, 50%‐100%). The median follow‐up interval was 6.6 months (range, 0.9 months‐26.8 months).

RESULTS:

The median overall survival time was 10.8 months, and 66.7% of patients died of disease progression. After HSRT treatment of 52 brain lesions, 13 lesions demonstrated complete responses, 12 lesions demonstrated partial responses, 22 lesions demonstrated stable disease, and 5 lesions demonstrated progressive disease. Actuarial local tumor control rates at 6 months and 1 year were 93.9% and 68.2%, respectively. Maximum tumor dimension, concurrent chemotherapy, and a tumor volume <1 cc were found to be statistically significant factors for local tumor control. One patient had a grade 3 toxicity (according to National Cancer Institute Common Terminology Criteria for Adverse Events).

CONCLUSIONS:

HSRT provides a high level of tumor control with minimal toxicity comparable to single‐fraction stereotactic radiosurgery (SRS). The results of the current study warrant a prospective randomized study comparing single‐fraction SRS with HSRT in this patient population. Cancer 2009. © 2009 American Cancer Society.     

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.     

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

BACKGROUND

Metastases to the brain from ovarian and endometrial carcinoma are uncommon and to the authors' knowledge consensus regarding optimal management is lacking. Stereotactic radiosurgery (SRS) has proven useful for the treatment of many benign and malignant brain tumors. In the current study, the authors evaluated outcomes after SRS in patients with ovarian and endometrial carcinoma.

METHODS

Twenty‐seven patients with brain metastases underwent gamma–knife SRS. Six patients had endometrial carcinoma, whereas 21 patients had ovarian carcinoma. Eighteen patients also received whole–brain radiotherapy. A total of 68 tumors were treated with gamma–knife SRS.

RESULTS

At the time of last follow–up, 1 patient was still alive and 26 had died. The median survival was 7 months after the initial diagnosis of brain metastasis and 5 months after SRS. The 1‐year survival rate after radiosurgery was 15% and that from the diagnosis of brain metastases was 22%. On final imaging, all tumors were controlled without further growth. Two patients (7.4%) developed new or progressive neurologic deficits after SRS.

CONCLUSIONS

SRS is an acceptable choice for the treatment of brain metastases resulting from ovarian and endometrial carcinoma, and provides local tumor control with limited morbidity. Careful patient selection is warranted in the setting of patients with uncontrolled systemic disease in whom a limited survival benefit is expected. Cancer 2008. © 2008 American Cancer Society.     

Salvage stereotactic radiosurgery for breast cancer brain metastases: outcomes and prognostic factors

BACKGROUND:

Salvage stereotactic radiosurgery (SRS) is often considered in breast cancer patients previously treated for brain metastases. The goal of this study was to analyze clinical outcomes and prognostic factors for survival in the salvage setting.

METHODS:

The authors retrospectively examined 79 consecutive breast cancer patients who received salvage SRS (interval of >3 months after initial therapy), 76 of whom (96%) received prior whole‐brain radiation therapy. Overall survival (OS) and central nervous system (CNS) progression‐free survival rates were calculated from the date of SRS using the Kaplan‐Meier method. Prognostic factors were evaluated using the Cox proportional hazards model.

RESULTS:

Median age was 50.5 years. Fifty‐eight percent of this population was estrogen receptor positive, 62% was HER2 positive, and 10% was triple negative. At the time of SRS, 95% had extracranial metastases, with 81% of extracranial metastases at other visceral sites (lung/pleura/liver). Forty‐eight percent had stable extracranial disease. Median interval from initial brain metastases therapy to SRS was 8.4 months. Median CNS progression‐free survival after SRS was 5.7 months (interquartile range [IQR], 3.6‐11 months), and median OS was 9.8 months (IQR, 3.8‐18 months). Eighty‐two percent of evaluable patients received further systemic therapy after SRS. HER2 status (adjusted hazard ratio [HR], 2.4; P = .008) and extracranial disease status (adjusted HR, 2.7; P = .004) were significant prognostic factors for survival on multivariate analysis.

CONCLUSIONS:

In patients with good Karnofsky performance status, salvage SRS for breast cancer brain metastases is a reasonable treatment option, given an associated median survival in excess of 9 months. Furthermore, patients with HER2‐positive tumors at diagnosis or stable extracranial disease at the time of SRS have an improved clinical course, with median survival of >1 year. Cancer 2012. © 2011 American Cancer Society.     

Dynamic stereotactic radiosurgery in the palliative treatment of cerebral metastatic tumors

From October 1988 to April 1990, 9 patients with metastatic brain disease (11 lesions) underwent stereotactic radiosurgery. All patients but two had recurrent metastatic disease after previous brain irradiation. The patients were treated with a single dose of 20 Gy, delivered to spherical target volumes ranging in diameters from 10 mm to 30 mm and prescribed to the 90% isodose surface. All tumors treated showed a favorable response to the treatment, with 4 patients achieving a complete radiological disappearance of the tumor. The majority of the patients experienced a rapid clinical improvement of their symptoms. No complications attributable to the radiosurgical treatment were seen. Stereotactic radiosurgery appears to be an effective and safe treatment for patients with recurrent metastatic brain disease.     

Biochemotherapy of metastatic melanoma in patients with or without recently diagnosed brain metastases

BACKGROUND: Brain metastases are an alarming complication of advanced melanoma, frequently contributing to patient demise. The authors performed a retrospective analysis to determine whether the treatment of metastatic melanoma with biochemotherapy would result in similar outcomes if brain metastases were first controlled with aggressive, central nervous system (CNS)-directed treatment. METHODS: Seventy melanoma patients were treated with biochemotherapy for metastatic melanoma between 1999 and 2005. Of these, 20 patients had recently diagnosed brain metastases, whereas 50 did not. Brain metastases (if present) were treated with stereotactic radiosurgery >or=28 days prior to systemic therapy. All patients were treated with biochemotherapy consisting of either dacarbazine or temozolomide in combination with a 96-hour continuous intravenous infusion of interleukin-2 and subcutaneous interferon-alpha-2B. The primary endpoint was survival from the time of the initial diagnosis of metastatic disease. RESULTS: Median survival from the time of the diagnosis of metastatic melanoma was 15.8 months for patients with brain metastases and 11.1 months for those without CNS involvement (P = .26 by the log-rank test; P = .075 by the Gehan Wilcoxon test). Dacarbazine-based and temozolomide-based regimens appeared similar with regard to their effect on overall survival and CNS disease progression. A plateau in further brain recurrences was observed in patients who survived for > 20 months. CONCLUSIONS: Data from the current study suggest that the outcome of biochemotherapy is comparable in patients with and those without brain metastases, if brain metastases are controlled with multidisciplinary treatment. Prolonged survival can be achieved in approximately 15% of patients, regardless of whether or not brain metastases are present.     

Stereotactic radiosurgery for multiple brain metastases

Stereotactic radiosurgery (SRS) alone has become one of the treatment options for patients with 1–4 metastases as the detrimental effects of whole brain radiation therapy on neurocognition and quality of life are becoming well known. Multiple randomized control trials also failed to show overall survival benefit of adding whole brain radiation therapy to SRS. However, the role of SRS in multiple brain metastases, especially those with ≥4 tumors, remains controversial. The literature is emerging, and the limited evidence suggests that the local control benefit is independent of the number of metastases, and that patients with more than four brain metastases have similar overall survival compared to those with 2–4 tumors. This review aims at summarizing the current evidence of SRS for multiple brain metastases, divided into limited (2–3) and multiple (≥4) lesions. It also reviews the technical aspects and cost–effectiveness of SRS.     

Immunotherapy in association with stereotactic radiotherapy for non-small cell lung cancer brain metastases: results from a multicentric retrospective study on behalf of AIRO

BackgroundTo define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology).MethodsNSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT.ResultsOne hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate.ConclusionsCombined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT.