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.     

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.     

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.     

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.     

Radiosurgery for re-irradiation of brain metastasis: results in 54 patients.

PURPOSE: To evaluate in terms of probabilities of local-regional control and survival, as well as of treatment-related toxicity, results of radiosurgery for brain metastasis arising in previously irradiated territory. PATIENTS AND METHODS: Between January 1994 and March 2000, 54 consecutive patients presenting with 97 metastases relapsing after whole brain radiotherapy (WBRT) were treated with stereotactic radiotherapy. Median interval between the end of WBRT and radiosurgery was 9 months (range 2-70). Median age was 53 years (24-80), and median Karnofski performance status (KPS) 70 (60-100). Forty-seven patients had one radiosurgery, five had two and two had three. Median metastasis diameter and volume were 21 mm (6-59) and 1.2 cc (0.1-95.2), respectively. A Leksell stereotactic head frame (Leksell Model G, Elektra, Instrument, Tucker, GA) was applied under local anesthesia. Irradiation was delivered by a gantry mounted linear accelerator (linacs) (Saturne, General Electric). Median minimal dose delivered to the gross disease was 16.2 Gy (11.8-23), and median maximal dose 21.2 Gy (14- 42). RESULTS: Median follow-up was 9 months (1-57). Five metastases recurred. One- and 2-year metastasis local control rates were 91.3 and 84% and 1- and 2-year brain control rates were 65 and 57%, respectively. Six patients died of brain metastasis evolution, and three of leptomeningeal carcinomatosis. One- and 2-year overall survival rates were 31 and 28%, respectively. According to univariate analysis, KPS, RPA class, SIR score and interval between WBRT and radiosurgery were prognostic factors of overall survival and brain free-disease survival. According to multivariate analysis, RPA was an independent factor of overall survival and brain free-disease survival, and the interval between WBRT and radiosurgery longer than 14 months was associated with longer brain free-disease survival. Side effects were minimal, with only two cases of headaches and two of grade 2 alopecia. CONCLUSION: Salvage radiosurgery of metastasis recurring after whole brain irradiation is an effective and accurate treatment which could be proposed to patients with a KPS>70 and a primary tumour controlled or indolent. We recommend that a dose not exceeding 14 Gy should be delivered to an isodose representing 70% of the maximal dose since local control observed rate was similar to that previously published in literature with upper dose and side effects were minimal.     

Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases

PURPOSE: To evaluate the feasibility and efficacy of hypofractionated stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS AND MATERIALS: The records of 69 patients with 174 metastatic liver lesions treated with SBRT between April 2001 and October 2004 were reviewed. The most common primary tumors were colorectal (n = 20), breast (n = 16), pancreas (n = 9), and lung (n = 5). The mean number of lesions treated per patient was 2.5 (range, 1-6). The longest diameter of the lesions ranged in size from 0.6 to 12.2 cm (median, 2.7 cm). Dose per fraction ranged from 2 Gy to 6 Gy, with a median total dose of 48 Gy (range, 30-55 Gy). Dose was prescribed to the 100% isodose line (IDL), with the 80% IDL covering the gross tumor volume with a minimum margin of 7 mm. RESULTS: The median follow up was 14.5 months. Sixty patients were evaluable for response based on an abdominal computed tomography scan obtained at a minimum of 3 months after completion of SBRT. The actuarial overall infield local control rate of the irradiated lesions was 76% and 57% at 10 and 20 months, respectively. The median overall survival time was 14.5 months. The progression-free survival rate was 46% and 24% at 6 and 12 months, respectively. None of the patients developed Grade 3 or higher toxicity. CONCLUSION: Hypofractionated SBRT provides excellent local control with minimal side effects in selected patients with limited hepatic metastases.     

射波刀治疗脑干转移瘤的疗效与预后分析

  目的  评价射波刀治疗脑干转移瘤的疗效和安全性。  方法  回顾性分析2013年1月至2018年1月于天津医科大学肿瘤医院接受射波刀治疗的49例患者,共55个脑干转移瘤病灶,总结患者治疗后总生存时间和局部控制率。分析性别、年龄、肿瘤部位、肿瘤大小、原发灶病理、KPS评分、术前是否行全脑放疗等对射波刀治疗脑干转移瘤预后的影响。  结果  中位肿瘤体积为1.96（0.1~15.6）cm3,总剂量8.0~40.0 Gy,1~5次/d,中位单次等效处方剂量（α/β=10）为18.2（8.0~23.7）Gy。中位最大单次等效剂量为25.2（11.8~37.4）Gy。局部控制率87.3%,15个病灶完全缓解（complete response,CR）,27个病灶部分缓解（partial response,PR）,6个病灶病变稳定（stable disease,SD）。中位生存时间为14（1~43）个月,中位无进展生存期为17.4个月。治疗后半年、1年、2年的生存率分别为75.5%、55.1%、28.6%。  结论  射波刀治疗脑干转移瘤安全有效,射波刀无框架,患者接受度好,分次照射可以用于治疗体积较大的肿瘤,脑干放射性反应发生率低。      

The impact of whole-brain radiation therapy on the long-term control and morbidity of patients surviving more than one year after gamma knife radiosurgery for brain metastases

PURPOSE: To better analyze how whole-brain radiotherapy (WBXRT) affects long-term tumor control and toxicity from the initial stereotactic radiosurgery (SRS) for brain metastases, we studied these outcomes in patients who had survived at least 1 year from SRS. METHODS AND MATERIALS: We evaluated the results of gamma knife radiosurgery for 160 brain metastases in 110 patients who were followed for a median of 18 months (range, 12-122 months) after SRS. Eighty-two patients had a solitary brain metastasis and 28 patients had multiple metastases. Seventy patients (116 tumors) were treated with initial radiosurgery and WBXRT, whereas 40 patients (44 lesions) initially received radiosurgery alone. Median treatment volume was 1.9 cc in the entire group, 2.3 cc in the WBXRT group, and 1.6 cc in the SRS alone group. Median tumor dose was 16 Gy (range, 12-21 Gy). RESULTS: At 1, 3, and 5 years, local tumor control was 84.1% +/- 5.5%, 68.6% +/- 8.7%, and 68.6% +/- 8.7% with SRS alone compared with 93.1% +/- 2.4%, 87.7% +/- 4.9%, and 65.7% +/- 10.2%. with concurrent WBXRT and SRS (p = 0.0228, univariate). We found that WBXRT improved local control in patient subsets tumor volume > or =2 cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and lung cancer metastases (p = 0.0069, 0.0080, 0.0083, 0.0184, and 0.0348). Distal intracranial failure developed at 1, 3, and 5 years in 26.0% +/- 7.1%, 74.5% +/- 9.4%, and 74.5% +/- 9.4% with SRS alone compared with 20.7% +/- 4.9%, 49.0% +/- 8.7%, and 61.8% +/- 12.8% with concurrent WBXRT and SRS (p = 0.0657). We found a trend for improved distal intracranial control with WBXRT for only nonradioresistant tumors (p = 0.054). Postradiosurgery complications developed in 2.8% +/- 1.2% and 10.7% +/- 3.5% at 1 and 3-5 years and was unaffected by WBXRT (p = 0.7721). WBXRT did not improve survival in the entire series (p = 0.5027) or in any subsets. CONCLUSIONS: In this retrospective study of 1-year survivors of SRS for brain metastases, the addition of concurrent WBXRT to SRS was associated with an improved local control rate in patient subsets with tumor volume > or =2 cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and specifically lung cancer metastases. A trend was noted for improved distal intracranial control for patients having nonradioresistant tumors. Distant intracranial relapse >1 year posttreatment is a significant problem with or without initial WBXRT.     

Radiosurgery for brain metastases: the Tuebingen experience.

PURPOSE: To retrospectively investigate the effectiveness of linear accelerator based radiosurgery (RS) in the treatment of brain metastases (BM). MATERIAL AND METHODS: Of 55 patients with a total of 72 BM, 41 patients had a single brain metastasis and 14 patients had two or three metastases. Median tumour dose of 15Gy (range 8-20Gy) was prescribed to a median isodose surface of 90% (range 70-100%) encompassing the target volume. RESULTS: The median survival time (MST) for all 55 patients was 7 months [95% confidence interval (CI), 5-10 months] and 2-year survival is 18%. There was no significant difference between patients who had one brain metastasis and those with either two or three metastases (log rank P=0.7565). Multivariate analysis in patients with a single BM showed that interval between primary diagnosis (PD) to BM, maximum size of metastasis, and histology (renal cell carcinoma and melanoma versus others) were independent prognostic factors influencing survival. Local control was obtained in 66/72 (92%) metastases. Actuarial local control at 24 months was 52%. Only age (50 years) and histology (renal cell versus others) influenced local control in the univariate analysis in patients with a single BM. In multivariate analysis, size, histology (renal cell and melanoma versus others), activity of extracranial metastatic disease, age, interval from PD to BM and location (midline versus other) independently influenced local control, while the dose was not significant for our patient group. Only one patient developed radiographically suspected RS-induced necrosis after previous whole brain RT. CONCLUSION: RS was effective and little toxic in BM. Identification of prognostic factors must be performed to gain knowledge on patients most likely to benefit from this procedure.     

Stereotactic radiosurgery as a therapeutic strategy for intracranial metastatic prostate carcinoma

Intracranial metastatic prostate carcinoma is rare. We sought to determine the clinical outcomes after Gamma Knife^® stereotactic radiosurgery (GKSRS) for patients with intracranial prostate carcinoma metastases. We studied data from 10 patients who underwent radiosurgery for 15 intracranial metastases (9 dural-based and 6 parenchymal). Six patients had radiosurgery for solitary tumors and four had multiple tumors. The primary pathology was adenocarcinoma (eight patients) and small cell carcinoma (two patients). All patients received multimodality management for their primary tumor (including resection, radiation therapy, androgen deprivation therapy) and eight patients had evidence of systemic disease at time of radiosurgery. The mean tumor volume was 7.7 cm³ (range 1.1–17.2 cm³) and a median margin dose of 16 Gy was administered. Two patients had progressive intracranial disease in spite of fractionated partial brain radiation therapy (PBRT) prior to SRS. A local tumor control rate of 85% was achieved (including patients receiving boost, upfront and salvage SRS). New remote brain metastases developed in three patients (33%) and one patient had repeat SRS for tumor recurrence. The median survival after radiosurgery was 13 months and the 1-year survival rate was 60%. SRS was a well tolerated and effective therapy either alone or as a boost to fractionated radiation therapy in the management of patients with intracranial prostate carcinoma metastases.     

Stereotactic radiosurgery for focal leptomeningeal disease in patients with brain metastases

Leptomeningeal disease (LMD) is well described in patients with brain metastases, presenting symptomatically in approximately 5% of patients. Conventionally, the presence of LMD is an indication for whole brain radiation therapy (WBRT) and not suitable for stereotactic radiosurgery (SRS). The purpose of the study was to evaluate the local control and overall survival of patients who underwent SRS to focal LMD. We reviewed our prospective registry and identified 32 brain metastases patients with LMD, from a total of 465 patients who underwent SRS between 2013 and 2015. Focal LMD was targeted with SRS in 16 patients. The median imaging follow-up time was 7 months. The median volume of LMD was 372 mm³ and the median margin dose was 16 Gy. Five patients underwent prior WBRT. Histology included non-small cell lung (8), breast (5), melanoma (1), gastrointestinal (1) and ovarian cancer (1). Follow-up MR imaging was available for 14 patients. LMD was stable in 5 and partially regressed in 8 patients at follow-up. One patient had progression of LMD with hemorrhage 5 months after SRS. Seven patients developed distant LMD at a median time of 7 months. The median actuarial overall survival from SRS for LMD was 10.0 months. The 6-month and 1-year actuarial overall survival was 60% and 26% respectively. Six patients underwent WBRT after SRS for focal LMD at a median time of 6 months. Overall, focal LMD may be may be treated successfully with radiosurgery, potentially delaying WBRT in some patients.     

Re-irradiation with radiosurgery for recurrent glioblastoma multiforme

Local tumor control remains a significant challenge in patients with glioblastoma multiforme (GBM). Despite aggressive radiation therapy approaches, most recurrences are within the high-dose field, limiting the ability to safely re-irradiate recurrence using conventional techniques. Fractionated stereotactic radiosurgery (fSRS) is a technique whose properties make it useful for re-irradiation. We retrospectively reviewed the charts of 14 patients with recurrent GBM treated with salvage radiosurgery. Seven patients were male and seven were female with a median age of 58 (range: 39-76). All patients had prior cranial radiation therapy to a median dose of 60 Gy (58-69). There were 18 lesions treated with a median tumor volume of 6.97 cm3 (0.54-50.0 cm3). fSRS was delivered in 1-3 fractions to a median dose of 24 Gy (18-30 Gy). Median follow-up for the cohort was 8 months (3-22 months). On follow-up MRI, 8 of 18 lesions had a radiographic response. The median time-to-progression following primary irradiation was 8 months (1-28 months) while the median time-to-progression (TTP) following fSRS was 5 months (1-16 months). Median local control following re-irradiation was 5 months and actuarial local control was 21% at 1-year. Overall survival following primary irradiation was 79% at 12 months and 46% at 2 years. Overall survival following re-irradiation was 79% at 6 months and 30% at 1 year. No significant treatment-related toxicity was seen in follow-up. These results indicate that re-irradiation for recurrent GBM using fSRS is well-tolerated and can offer a benefit in terms of progression-free survival (PFS).     

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.     

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?%.     

Radiotherapeutic management of brain metastases from breast cancer

We have reviewed the medical records of 28 breast cancer patients with brain metastases who were treated with radiotherapy at our clinic from 1980 through 1994 (4 patients, postoperatively; 24 patients, radiotherapy alone). Radiotherapy was delivered as whole brain irradiation using lateral opposed 10 MV X-rays. Ten patients received an additional boost to a reduced field. One patient was treated with localized stereotactic irradiation alone. The radiation dose for tumors ranged from 32 Gy to 60 Gy (mean, 49 Gy) in 2 or 3 Gy daily fractionated doses. The brain was the first site of metastatic involvement in only two patients. In the 26 evaluable patients, neurologic functional improvement was achieved in 24 patients (92%) with complete response (CR) in 1 2 patients (46%) and partial response (PR) in 1 2 patients (46%). The survival rates from the initial treatment were 39% at 5 years and 16% at 10 years (median survival time, 50 months), and those after treatment of brain metastases were 29% at one year and 18% at 2 years (median survival time, 6 months). Performance status tended to be associated with survival (p=0.10), and the presence of liver metastasis was the most important risk factor concerning survival (p=0.056). Two patients suffered severe chronic complications. One patient developed severe dementia after whole brain irradiation with a total dose of 45 Gy in 3 Gy daily fractionated dose, and another patient developed widespread brain necrosis after combined radiotherapy with intrathecal local infusion of methotrexate. Radiotherapeutic management is useful for breast cancer patients with brain metastasis, and long-term survival may also be possible even if patients have preexisting extracranial metastases, except for hepatic involvement. Radiation-related complications should therefore be avoided in these patients.     

Treatment of brain metastases in patients with non-small cell lung cancer (NSCLC) by stereotactic linac-based radiosurgery: prognostic factors

A restrospective study of patients with brain metastases from non-small cell lung cancer (NSCLC) is performed to identify patients who benefit from radiosurgery and to determine prognostic factors for survival. Eighty-six consecutive patients with a total of 110 brain metastases from NSCLC were treated with linac-based radiosurgery. Six patients with eight brain metastases who received radiosurgery as a focal boost to whole brain radiotherapy where excluded. Median age at treatment was 60 years. Median dose was 20 Gy/80%-isodose. A chi(2)-test was used to identify potential prognostic factors for local control of brain metastases and survival of the patients. Median follow-up was 6 months (range 1 1/2-77 months) with 17/80 patients still alive. Median actuarial survival was significantly longer (P<0.004) in patients with metachronous onset of brain metastases in comparison to synchronous onset (8.3 vs. 3.3 months). Survival was significantly increased after radiosurgery in the absence of extracranial tumor progression (P<0.03). Eleven patients (14%) developed new brain metastases after radiosurgery after a latency of median 5 months. Actuarial local control rate was 96% after 3 months. Local control was significantly increased with a prescribed dose > or=18 Gy/80%-isodose (P<0.01). We conclude that especially patients with poor prognostic factors and a limited number of brain metastases may be palliatively treated with radiosurgery alone. This approach allows to effectively control CNS manifestation of the disease and can be integrated into chemotherapeutic protocols.     

Factors associated with tumor response and survival in radiosurgery for brain metastasis

Background We reviewed our experience with radiosurgery for brain metastasis and focused on factors associated with tumor response and survival. Methods Our study consists of 19 patients with 25 brain metastases who underwent linear accelerator radiosurgery. There was evidence of extra-central nervous system (CNS) tumors in 15 patients. The maximum diameter of the tumors ranged from 3 to 40 mm with a mean of 20 mm. Tumor doses at the isocenter varied from 16 to 25 Gy with a mean of 21 Gy. Eighteen lesions were treated by radiosurgery alone and 7 lesions received combined radiosurgery with fractionated radiotherapy. Of the 11 patients who experienced CNS failure either in or out of the radiosurgery field, 6 patients had salvage radiotherapy. Results Median survival was 7 months, and the 1-year actuarial survival rate was 40%. Death was due to extra-CNS tumor manifestations in 11 patients. In 3 patients, CNS failure was the cause of death. One died of local progression, and the other 2 died of newly developed metastases. Poor Karnofsky performance scores and the presence of extra-CNS tumors significantly affected 1-year survival in univariate analysis (P<0.05). Local tumor control was achieved in 80% of the lesions. The 1-year actuarial tumor control rate was 51%. Newly developed brain metastases were observed in 7 patients. The tumor diameter was mostly associated with tumor response in multiple regression analysis (P=0.0031). Conclusion We concluded that radiosurgery is effective in controlling small brain metastasis. Survival benefit is expected for those with good performance status and adequately controlled extra-CNS disease. Part of this work was presented at the 7th Asian and Oceanian Congress of Radiology, Kuala Lumpur, Malaysia, May 28-June 1, 1995.     

Stereotactic radiosurgery for brainstem metastases: Survival, tumor control, and patient outcomes

PURPOSE: Patients with brainstem metastases have limited treatment options. In this study, we reviewed outcomes after stereotactic radiosurgery (SRS) in the management of patients with brainstem metastases. METHODS AND MATERIALS: Records were reviewed of 22 consecutive patients presenting with brainstem metastases who underwent SRS. The most frequent primary malignancy was the lung (n = 11), followed by breast (n = 3) and kidney (n = 2). Three patients (14%) also underwent whole-brain radiation therapy (WBRT). The median tumor volume was 0.9 mL (range, 0.1-3.3 mL); the median tumor margin dose was 16 Gy (range, 14-23 Gy). RESULTS: Median survival time after SRS was 8.5 months. Although local tumor control was achieved in all patients with imaging follow-up (n = 19), 5 patients died from development and progression of new brain metastases. Two patients (9%) had symptom improvement after SRS, whereas 1 patient (5%) developed a new hemiparesis after SRS. CONCLUSIONS: Radiosurgery is safe and provides a high local tumor control rate for patients with small brainstem metastases. Patients with limited systemic disease and good performance status should be strongly considered for SRS.     

Transient enlargement of contrast uptake on MRI after linear accelerator (linac) stereotactic radiosurgery for brain metastases

Purpose/Objective: With the increasing number of patients successfully treated with stereotactic radiosurgery for brain metastases, decision making after therapy based on follow-up imaging findings becomes more and more important. Magnetic resonance imaging (MRI) is the most sensitive means for follow-up studies. The objective of this study was to investigate the treatment outcome of our radiosurgery program and to describe the response of brain metastases to contrast-enhanced MRI after linear accelerator (linac) stereotactic radiosurgery and identify factors to distinguish among local control and local failure.

Methods and Materials: Using serial MRI, we followed the course of 87 brain metastases in 48 consecutive patients treated between September 1996 and November 1997 with linac-based radiosurgery with 15-MV photons. Treatment planning was performed on an MR data cube. For spherical metastases, radiosurgery was delivered using a 9 noncoplanar arc technique with circular-shaped collimators. For irregularly shaped targets, radiosurgery was delivered using a manually driven multi-leaf collimator with a leaf width of 1.5 mm projected to the isocenter. Median radiosurgery dose was 20 Gy prescribed to the 80% isodose. Together with whole brain radiotherapy (20 × 2 Gy, 5/w), a median radiosurgical dose of 15 Gy was delivered. Median follow-up was 8 (range 2–36) months. Factors influencing local control and survival rates were analyzed with respect to MRI response, and Kaplan-Meier curves were calculated.

Results: Actuarial local tumor control was 91% at one and two years. Patient survival at one and two years was 30% and 18%. Median survival was 9 months. During follow-up in 70 (81%) of the 87 treated metastases, the contrast-enhancing volumes on T1W images were stable or disappeared partly or completely. A transient enlargement of contrast-enhancing volumes was observed in 11 (12%) of the 87 lesions treated, while a progressive enlargement due to local treatment failure was observed in 6 (7%) of the 87 treated metastases. Younger age, early contrast onset after radiosurgery, and previous chemotherapy were associated with this transient enlargement of contrast-enhancing lesion volume.

Conclusions: Linac-based radiosurgery is an effective, noninvasive, and safe treatment option for patients with brain metastases. A marked enlargement of the contrast-enhancing volume on T₁-weighted MR images after radiosurgery is a sensitive predictor for, but not equivalent with, local failure. In as many as two-thirds of the cases with contrast enlargement in MRI follow-up, the contrast enlargement is transient with no need for further treatment. While some MRI findings are more likely if transient enlargement is present, a clear decision cannot be made based on MRI, and ultimately the clinical status dictates further action.     

LINAC Radiosurgery as Single Treatment in Cerebral Metastases

Summary Objective: Stereotactic radiosurgery is a radiation technique of high radiation dose focused on a stereotactic intracranial target in a single fraction with high precision. LINAC Radiosurgery has gained increasing relevance in the treatment of brain metastases since it was introduced by Sturm (1987). Method and patient selection: From January 1996 to August 2003 110 patients were treated with LINAC Radiosurgery. A combination of the University of Florida system and the X Knife System developed by Radionics was used in all patients. Seventy patients had a single and 40 patients multiple metastatic lesions at the time of diagnosis and treatment. Overall 161 intracerebral metastases were treated. Median tumor volume was 3.1 ccm (0.3–15 ccm). Median radiation dose to the tumor margin was 1830 cGy (range 1100–2200 cGy) prescribed to the 80% isodose line. Whole brain radiation therapy with a total dose of 30 Gy in 10 fractions was performed in 35 patients because of multiple metastases and LINAC Radiosurgery was used as boost for recurrences. In 75 patients LINAC Radiosurgery was used as single treatment. Results: The follow-up period was between 6 and 72 months. Local tumor control rate was 89.4%. Seventeen out of 161 metastases treated showed local recurrence. Eleven out of 75 patients treated with radiosurgery as single treatment developed distant recurrence and 3 out of 35 patients who were treated with whole brain radiation therapy (WBRT) and radiosurgery as boost. The 1-year survival rate is 54.9% with a median survival of 54 weeks. Conclusion: LINAC Radiosurgery is an effective and safe treatment modality in patients with cerebral metastases located in any area of the brain. WBRT should be preserved for patients with multiple metastases or be delayed until multiple recurrence occurs. Surgery is still the treatment of choice in metastases with mass effect and surgical accessible location.