Chemosensitized radiosurgery for recurrent brain metastases

Temozolomide is known to penetrate the blood?Cbrain barrier and sensitize brain tumors to radiation and has been used clinically to sensitize fractionated external beam radiotherapy. However, there are limited prospective clinical data available on the safety of temozolomide as a chemosensitizing agent administered with stereotactic radiosurgery. This is a phase I trial of previously irradiated patients with one to four progressive brain metastases and Karnofsky performance scale score ??60?% enrolled in three sequential cohorts: temozolomide 100, 150 or 200?mg/(m² day) administered for 5?days. Stereotactic radiosurgery (SRS) was administered on day 5. The SRS dose was dependent on target diameter: 15?Gy (31?C40?mm), 18?Gy (21?C30?mm) or 21?Gy (<20?mm). The primary endpoint was safety of increasing temozolomide doses. Secondary endpoints included local control and survival. 26 subjects were enrolled and 49 total metastatic lesions were treated. The median number of brain metastases was 1.5, with a median target diameter of 21?mm. The most common grade 1?C2 adverse events irrespective of causality were vomiting (23?%), nausea (23?%), edema (12?%), seizure (8?%), psychosis (4?%) and thrombocytopenia (4?%). The frequency of nausea and vomiting did not appear to be dose-dependent. Grade 3?C4 toxicities were not observed. Median overall survival was 10.2?months. Crude local control was 87.5?%, with a radiological response seen in eight of 24 evaluable patients (33.3?%), and stable disease >6?months in 13 of 24 patients (54.2?%). Temozolomide, at doses up to 200?mg/(m² day)?×?5?days, prior to SRS is well tolerated, with no dose-limiting toxicities in patients with recurrent brain metastases. Local control of target lesions was >80?%.     

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.     

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。     

Stereotactic radiosurgery for metastatic brain tumors

We report on a prospective phase TI study utilizing stereotactic radiosurgery for patients with intracranial parenchymal metastases. Fifty patients ranging in age from 38 to 77 years with 1 to 3 intraparenchymal brain metastases were treated with stereotactic radiosurgery either immediately following whole brain radiotherapy or at the time of intracranial disease progression following failure of whole brain radiotherapy. Twenty patients treated with adjuvant therapy received a median radiosurgical dose of 20 Gy. Thirty patients treated with salvage therapy received a median radiosurgical dose of 20 Gy. No immediate neurotoxicity was seen following radiosurgery however, 4 patients (8%) developed symptomatic radiation necrosis. Median survival was 6.5 and 6.0 months for patients treated with adjuvant and salvage radiosurgery respectively. In patients with oligometastatic brain metastases manifesting intracranial disease progression after whole brain radiotherapy, salvage radiotherapy appears to offer improved palliation when compared to retreatment with whole brain radiotherapy. The results of patients treated with up-front adjuvant radiosurgery when compared to historical controls treated with whole brain radiotherapy only are less clear as to benefit and require a phase III study before definitive recommendations can be made.     

脑转移瘤立体定向放射外科治疗

立体定向脑放疗放射外科(SRS)可治疗单发或多发脑转移瘤,与全脑放射治疗(WBRT)相比,能延长生存时间、提高生活质量.用于全身肿瘤控制或稳定、直径≤3.5cm单发脑转移瘤患者,具有与手术配合WBRT相似的疗效.SRS加WBRT与单纯SRS治疗相比,能提高颅内无进展生存期,但未能延长生存时间.脑转移瘤复发后SRS治疗能取得较好疗效.     

Stereotactic radiosurgery for brain tumors.

In the 50 years since Leksell developed the concepts and initial hardware for modern brain radiosurgery, the treatment has progressed to the point where it is used commonly for arteriovenous malformations, benign masses, and metastases. Radiosurgery offers patients an effective treatment of life-threatening lesions with a reasonably low risk for discomfort and injury. In the 1990s, the procedure was used widely as primary and adjuvant treatment. The difficulty of defining the boundaries of primary brain cancers makes determining treatment targets problematic. Better imaging and computing offer a bright future for the technology.     

Surgical resection and postoperative radiosurgery versus staged radiosurgery for large brain metastases

Journal of Neuro-Oncology - The purpose of this study was to retrospectively evaluate the new treatment paradigm of staged stereotactic radiosurgery (SRS) for the treatment of large brain...     

Linac-based stereotactic radiosurgery for brain arteriovenous malformations

Aims

Most papers dealing with radiosurgery for cerebral arteriovenous malformations (AVMs) present the results of gamma-knife treatment, whereas linac radiosurgery is becoming increasingly popular. Moreover, there is still much uncertainty about the rationale of combined endovascular and radiosurgical treatment. The aims of this study were to evaluate obliteration and rebleeding rates, and to determine factors influencing obliteration and adverse effects after linac-based stereotactic radiosurgery for cerebral AVMs.

Materials and methods

Records of 62 consecutive patients were analysed. Thirty-one had partial embolisation, five surgery, 29 had no prior treatment. The mean follow-up was 28.4 months. The mean volume treated was 11.7 cm³ and included embolised portions of AVMs. Actuarial obliteration rates and annual bleeding hazard rates after radiosurgery were calculated using Kaplan-Meier survival and life table analyses.

Results

Actuarial obliteration rates after 1, 2 and 3 years of follow-up were 17, 36 and 40%, respectively. Prior embolisation did not influence the obliteration rate. In 77.3% of patients, obliteration occurred during the first 2 years of follow-up. Annual bleeding hazard rates after stereotactic radiosurgery were 3.4 and 1.1% during the first and second year of follow-up, respectively. Non-symptomatic imaging abnormalities were detected in 33.9% of patients after a median time of 8.8 months. The Spetzler-Martin grade, AVM score, radiation dose, volume and AVM nidus < 3 cm significantly influenced the probability of obliteration. A dose less than 15 Gy significantly reduced the probability of obliteration.

Conclusion

At least a 3 year follow-up is required to accurately assess the outcome. The best effects of the treatment are achieved for small (<3 cm), low-grade lesions with a low AVM score. The bleeding risk after stereotactic radiosurgery gradually decreases.     

Single brain metastasis: radiosurgery alone compared with radiosurgery plus up-front whole-brain radiotherapy

BACKGROUND:

Neurosurgical resection is considered the standard treatment for most patients with a single brain metastasis. However, radiosurgery (RS) is a reasonable alternative. It was demonstrated that whole‐brain radiotherapy (WBRT) in addition to RS improves local control of 1‐3 brain metastases. Little information is available regarding WBRT in addition to RS for a single lesion.

METHODS:

Data of 63 patients who received RS alone for a single brain metastasis were retrospectively compared with 39 patients treated with WBRT+RS for local control of the treated metastasis, distant intracerebral control, and survival. Seven additional potential prognostic factors were investigated including age, sex, Karnofsky performance score, tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation.

RESULTS:

The 1‐year local control rates were 49% after RS and 77% after WBRT+RS (P = .040). The 1‐year distant control rates were 70% and 90%, respectively (P = .08). The 1‐year survival rates were 57% and 61%, respectively (P = .47). On multivariate analysis, improved local control was associated with WBRT+RS (risk ratio [RR], 1.95; P = .033) and interval from tumor diagnosis to irradiation >15 months (RR, 1.88; P = .042). Improved distant control was almost associated with WBRT+RS (RR, 2.24; P = .05) and age (RR, 2.20; P = .05). Improved survival was associated with KPS 90‐100 (RR, 1.73; P = .040), no extracerebral metastases (RR, 1.88; P = .013), RPA class 1 (RR, 2.06; P = .005), and interval from tumor diagnosis to irradiation >15 months (RR, 1.98; P = .009).

CONCLUSION:

The addition of WBRT to RS was associated with improved local control and distant intracerebral control but not survival. Cancer 2011;. © 2011 American Cancer Society.     

Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone

PURPOSE: To determine how the omission of whole brain radiotherapy (WBRT) affects the neurocognitive function of patients with one to four brain metastases who have been treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS: In a prospective randomized trial between WBRT+SRS and SRS alone for patients with one to four brain metastases, we assessed the neurocognitive function using the Mini-Mental State Examination (MMSE). Of the 132 enrolled patients, MMSE scores were available for 110. RESULTS: In the baseline MMSE analyses, statistically significant differences were observed for total tumor volume, extent of tumor edema, age, and Karnofsky performance status. Of the 92 patients who underwent the follow-up MMSE, 39 had a baseline MMSE score of < or =27 (17 in the WBRT+SRS group and 22 in the SRS-alone group). Improvements of > or =3 points in the MMSEs of 9 WBRT+SRS patients and 11 SRS-alone patients (p = 0.85) were observed. Of the 82 patients with a baseline MMSE score of > or =27 or whose baseline MMSE score was < or =26 but had improved to > or =27 after the initial brain treatment, the 12-, 24-, and 36-month actuarial free rate of the 3-point drop in the MMSE was 76.1%, 68.5%, and 14.7% in the WBRT+SRS group and 59.3%, 51.9%, and 51.9% in the SRS-alone group, respectively. The average duration until deterioration was 16.5 months in the WBRT+SRS group and 7.6 months in the SRS-alone group (p = 0.05). CONCLUSION: The results of the present study have revealed that, for most brain metastatic patients, control of the brain tumor is the most important factor for stabilizing neurocognitive function. However, the long-term adverse effects of WBRT on neurocognitive function might not be negligible.     

Resection versus radiosurgery for patients with brain metastases

Brain metastases occur in 20-40% of adult cancer patients and the incidence is apparently increasing. Despite advances in treatment, the prognosis of these patients is poor, with a median survival of approximately 4 months. Whole brain radiation therapy is the standard of care for most patients with brain metastases. Randomized trials have demonstrated that focal treatments, such as resection and radiosurgery, yield significant improvement in the survival of patients with a single metastasis. The utility of these strategies, specifically in terms of increased survival, is unclear in patients with more than one metastasis. In addition to focal treatments, future directions in the treatment of brain metastases include the development of intraoperative imaging capabilities, improved methods of identifying patients who are likely to benefit from treatment, systemic agents, such as chemotherapy and radiosensitizers, and the incorporation of targeted and antiangiogenic therapies.     

Stereotactic radiosurgery for the treatment of brain metastases

Background: The objective of this systematic review was to summarise the current evidence concerning radiosurgical treatment (SRS) of newly diagnosed brain metastasis and to compare SRS as a single or additional treatment to treatment alternatives with regard to medical effectiveness and safety.Methods: A structured search of electronic databases was performed to identify relevant publications from 2002 through 2007. Studies targeting patients with brain metastases were included. Standardised quality assessment and data extraction were performed.Results: Of 1496 publications, 16 studies were included. The mean survival in most studies was less than 12 months. There was evidence that SRS plus WBRT was associated with improved local tumour control and neurological functioning compared to either treatment alone. Only in patients with single metastasis, this resulted in improved survival. There was inconclusive evidence when comparing SRS to WBRT, Neurosurgery (NS) or Hypofractionated Radiotherapy (HCSRT). The Quality of life (Qol) was not investigated.Conclusion: SRS plus WBRT was associated with improved local tumour control and neurological functioning compared to either treatment alone. Only in certain patients, this resulted in improved survival. Methodologically rigorous studies are therefore warranted to investigate further treatment options, and in view of the poor prognosis, to investigate Qol and neurological functioning.     

Stereotactic radiosurgery for brain tumors in pediatric patients

Brain tumors represent the most common solid tumor in children. Fractionated radiation therapy has been an important treatment modality in the multi-disciplinary management of these tumors. Stereotactic radiosurgery is the precise delivery of a single fraction of radiation and has been an important treatment option for adult brain tumor patients. Although the use of stereotactic radiosurgery in pediatric brain tumors is much less frequent, it represents an important alternative for patients with recurrent, surgically inaccessible or radioresponsive tumors. This article will review the results and logistical issues of this modality in the management of pediatric brain tumors.     

Indications for resection and radiosurgery for brain metastases

PURPOSE OF REVIEW: This review is focused on indications for resection, stereotactic radiosurgery, and fractionated radiotherapy for patients with single or multiple brain metastases. Our purpose is to summarize the indications and effect of these management approaches. RECENT FINDINGS: Brain metastases are a frequent challenge in patients with extracranial solid cancers. More than 40% of patients with cancer will develop metastases to the brain. While some patients present with large lesions and symptoms related to mass effect, many are diagnosed when asymptomatic tumors are found on screening studies. The main options for patients with brain metastases are whole brain radiation therapy, surgical resection, and stereotactic radiosurgery. Much information regarding outcomes, survival, management morbidity, and quality of life is available. Randomized, class III clinical trials demonstrate that multimodal therapy is important for both life quality and extended survival. A better understanding of the current therapeutic options should result in improvements in patient care. SUMMARY: This is a review of the literature from May 2004 to June 2005 with special attention on publications related to effect on quality of life with different procedures and therapies.     

A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases

PURPOSE: Data collected from 10 institutions were reviewed to compare survival probabilities of patients with newly diagnosed brain metastases managed initially with radiosurgery (RS) alone vs. RS + whole brain radiotherapy (WBRT). METHODS AND MATERIALS: A database was created from raw data submitted from 10 institutions on patients treated with RS for brain metastases. The major exclusion criteria were resection of a brain metastasis and interval from the end of WBRT until RS >1 month (to try to ensure that the up-front intent was to combine RS + WBRT and that RS was not given for recurrent brain metastases). Survival was estimated using the Kaplan-Meier method from the date of first treatment for brain metastases until death or last follow-up. Survival times were compared for patients managed initially with RS alone vs. RS + WBRT using the Cox proportional hazards model to adjust for known prognostic factors or Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class. RESULTS: Out of 983 patients, 31 were excluded because treatment began after 6/1/98; 159 were excluded because brain metastases were resected; 179 were excluded because there was an interval >1 month from WBRT until RS; and 45 were excluded for other reasons. Of the 569 evaluable patients, 268 had RS alone initially (24% of whom ultimately had salvage WBRT), and 301 had RS + up-front WBRT. The median survival times for patients treated with RS alone initially vs. RS + WBRT were 14.0 vs. 15.2 months for RPA Class 1 patients, 8.2 vs. 7.0 months for Class 2, and 5.3 vs. 5.5 months for Class 3, respectively. With adjustment by RPA class, there was no survival difference comparing RS alone initially to RS + up-front WBRT (p = 0.33, hazard ratio = 1.09). CONCLUSIONS: Omission of up-front WBRT does not seem to compromise length of survival in patients treated with RS for newly diagnosed brain metastases.     

Stereotactic radiosurgery in elderly patients with brain metastases

Stereotactic radiosurgery (SRS) has been increasingly employed as an alternative to whole brain radiation therapy in patients with brain metastases, with the aim to reduce its potential toxicity. We have evaluated clinical outcomes of SRS as initial treatment for brain metastases in patients 70 years and older. Between November 2007 and October 2011, 102 patients of 70 years and older with 1–4 metastases were treated with SRS. The primary end point of the study was overall survival. Secondary end points were local control and distant failure rates, cause of death, performance measurements, and toxicity of treatment. At a median follow-up of 11.0 months (range 1–48 months), median survival and median time to distant failure were 13.2 and 10 months, respectively. The 1- and 2-year survival rates were 63 and 28 %, and respective distant failure rates were 54 and 78 %. Forty-five patients succumbed to their extracranial disease and 14 patients died of progressive intracranial disease. Nine patients recurred locally after SRS. The 1- and 2-year local control rates were 90 and 84 %, respectively. Evaluation of neurocognitive function using the Mini-Mental State Examination (MMSE) showed no significant neurocognitive decline after SRS. MMSE score improved in 15 % of patients, worsened in 12 % of patients, and remained stable in the others. Severe neurological complications were reported in 7 (7 %) patients, requiring surgery or medical treatment. Initial treatment with SRS with close monitoring may represent a relatively safe treatment strategy associated with survival benefit, with outcomes similar to those reported in historical series of SRS for younger patients.     

Observations on the role of brain stereotactic radiosurgery

As a research paradigAs a research paradigm （1） evaluated measures of animal performance correlated with markers of microglia activation and inflammation as they sought to see the effects of more focused radiation in two-month-old male athymic nude rats.The authors used intensity modulated radiation therapy （IMRT） and volumetric modulated arc therapy （VMAT） to irradiate the hippocampus either unilaterally or bilaterally.Treatment plans delivered a total dose of 10 Gy to either one or both hemispheres of the rat brain.Their data suggests that specific behavioral tasks could be reduced by focused radiation delivered to the hippocampus,and in unilaterally treated animals,the contralateral brain seemed to up-regulate repair mechanisms.This report provides additional information relative to the mechanisms of radiobiological effect using targeted radiation.     

Stereotactic radiosurgery for brain metastases from hepatocellular carcinoma

The purpose of this study is to investigate the possible role of stereotactic radiosurgery (SRS) in the management of patients with brain metastases from hepatocellular carcinoma (HCC). Thirty-two consecutive patients with 80 brain metastases from HCC were treated with SRS. Twenty-eight (87.5 %) patients were male, and the mean age of the patients was 54 ± 12 years (range 22–73). Twenty-seven (84.4 %) patients were classified as RTOG RPA Class 2. The mean tumor volume was 6.14 ± 11.3 cm³ (range 0.01–67.3). The mean marginal dose prescribed was 20.1 ± 3.6 Gy (range 10.0–25.0). The median overall survival time after SRS was 11.3 ± 5.8 weeks (95 % CI 0–22.7). A greater total volume of brain metastases (>14 cm³) was the only independent prognostic factor (HR = 2.419; 95 % CI 1.040–5.624; p = 0.040). The actuarial control rate of brain metastases was 51.3 % at 4 months after SRS. The prescribed marginal dose (>18 Gy) was significantly related with the actuarial tumor control (HR = 0.254; 95 % CI 0.089–0.725; p = 0.010). The prognosis of patients with brain metastases from HCC is dismal even with the modern technology of radiosurgery. The marginal dose prescribed should be reevaluated to improve upon the current poor local control rates.