Defining the role of radiosurgery in the management of brain metastases.

The role of stereotactic radiosurgery in the management of recurrent and newly diagnosed brain metastases was evaluated prospectively. From December 1988 to March 1991, 58 lesions in 40 patients were treated with accelerator-based stereotactic radiosurgery. All patients were followed for a minimum of 6 months or to death. The primary purpose was to determine the impact of radiosurgery on local control and its subsequent effects on quality of life. An overall tumor control rate of 82% with a complete response rate of 43% were achieved. As anticipated, the response rate for smaller tumors was substantially better than that for larger tumors (78% for lesions < 2 cm3; 50% for lesions > or = 10 cm3). Although the overall in-field progression rate was 18.5%, only 1/23 (4%) complete responders subsequently recurred. The in-field failure rate is highly comparable with recently published surgical data. Progression outside the brain was noted in two-thirds of patients. One quarter of the deaths were neurologic. The median survival for this minimally selected patient population was 6.5 months. Stereotactic radiosurgery was also associated with improved quality of life as measured by Karnofsky score, neurologic function, and steroid dependence. Long-term steroid dependence was encountered in only four patients. We conclude that stereotactic radiosurgery can be used effectively in patients with brain metastases. In this series, a high tumor response rate was achieved which was associated with improved quality of life.     

Phase II trial of radiosurgery for one to three newly diagnosed brain metastases from renal cell carcinoma, melanoma, and sarcoma: an Eastern Cooperative Oncology Group study (E 6397).

PURPOSE: Long-term brain metastases survivors are at risk for neurologic morbidity after whole-brain radiotherapy (WBRT). Retrospective radiosurgery (RS) reports found no survival difference when compared with WBRT. Before RS alone was evaluated with delayed WBRT in a phase III trial, the feasibility of RS alone was tested prospectively. PATIENTS AND METHODS: Patients with renal cell carcinoma, melanoma, or sarcoma; one to three brain metastases; and performance status of 0 to 2 were enrolled. Exclusion criteria were leptomeningeal disease; metastases in medulla, pons, or midbrain; or liver metastases. On the basis of tumor size, patients received 24, 18, or 15 Gy RS. At recurrence, management was discretionary. The primary end point was 3- and 6-month intracranial progression. RESULTS: Between July 1998 and August 2003, 36 patients were accrued; 31 were eligible. Median follow-up was 32.7 months and the median survival was 8.3 months (95% CI, 7.4 to 12.2). Three- and 6-month intracranial failure with RS alone was 25.8% and 48.3%. Failure within and outside the RS volume, when in-field and distant intracranial failures were scored independently, was 19.3% and 16.2% (3 months) and 32.2% and 32.2% (6 months), respectively. Approximately 38% of patients experienced death attributable to neurologic cause. There were three grade 3 toxicities related to RS. CONCLUSION: Intracranial failure rates without WBRT were 25.8% and 48.3% at 3 and 6 months, respectively. Delaying WBRT may be appropriate for some subgroups of patients with radioresistant tumors, but routine avoidance of WBRT should be approached judiciously.     

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.     

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.     

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.     

Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases.

PURPOSE: Multiple brain metastases are a common health problem, frequently diagnosed in patients with cancer. The prognosis, even after treatment with whole brain radiation therapy (WBRT), is poor with average expected survivals less than 6 months. Retrospective series of stereotactic radiosurgery have shown local control and survival benefits in case series of patients with solitary brain metastases. We hypothesized that radiosurgery plus WBRT would provide improved local brain tumor control over WBRT alone in patients with two to four brain metastases. METHODS: Patients with two to four brain metastases (all < or =25 mm diameter and known primary tumor type) were randomized to initial brain tumor management with WBRT alone (30 Gy in 12 fractions) or WBRT plus radiosurgery. Extent of extracranial cancer, tumor diameters on MRI scan, and functional status were recorded before and after initial care. RESULTS: The study was stopped at an interim evaluation at 60% accrual. Twenty-seven patients were randomized (14 to WBRT alone and 13 to WBRT plus radiosurgery). The groups were well matched to age, sex, tumor type, number of tumors, and extent of extracranial disease. The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients who had boost radiosurgery. The median time to local failure was 6 months after WBRT alone (95% confidence interval [CI], 3.5-8.5) in comparison to 36 months (95% CI, 15.6-57) after WBRT plus radiosurgery (p = 0.0005). The median time to any brain failure was improved in the radiosurgery group (p = 0.002). Tumor control did not depend on histology (p = 0.85), number of initial brain metastases (p = 0.25), or extent of extracranial disease (p = 0.26). Patients who received WBRT alone lived a median of 7.5 months, while those who received WBRT plus radiosurgery lived 11 months (p = 0.22). Survival did not depend on histology or number of tumors, but was related to extent of extracranial disease (p = 0.02). There was no neurologic or systemic morbidity related to stereotactic radiosurgery. CONCLUSIONS: Combined WBRT and radiosurgery for patients with two to four brain metastases significantly improves control of brain disease. WBRT alone does not provide lasting and effective care for most patients.     

Metastatic melanoma to the brain: prognostic factors after gamma knife radiosurgery

To identify important prognostic factors predictive of survival and tumor control in patients with metastatic melanoma to the brain who underwent gamma knife radiosurgery.

A total of 122 consecutive patients with 332 intracranial melanoma metastases underwent gamma knife radiosurgery over a 5-year period. Of these, 39 (32%) also received whole-brain irradiation (WBI). The median tumor volume was 0.8 cm³ (range: 0.02–30.20 cm³), and the median prescribed dose was 20 Gy (range: 14–24 Gy). Median follow-up was 6.8 months. Univariate and multivariate analyses of survival and freedom from progression were performed using the following parameters: status of systemic disease, intracranial tumor volume, number of lesions, tumor location, Karnofsky performance status, gender, age, and WBI.

Overall median survival was 7.0 months from time of radiosurgery and 9.1 months from the onset of brain metastasis. In multivariate analysis, improved survival was noted in patients with total intracranial tumor volume <3 cm³ (p = 0.003) and inactive systemic disease (p = 0.0065), whereas other parameters studied were of lesser importance (tumor location, p = 0.056, and Karnofsky performance status, p = 0.086), or of no significance (number of lesions, WBI, age, and gender). Freedom from subsequent brain metastasis depended on intracranial tumor volume (p = 0.0018) and status of systemic disease (p = 0.034).

Conclusions: Stereotactic radiosurgery is an effective treatment modality for patients with intracranial metastatic melanoma. Tumor volume and status of systemic disease are good independent predictors of survival and freedom from tumor progression.     

Progression of the lung cancer primary correlates with the identification of new brain metastases after initial radiosurgery

We retrospectively evaluated the relationship between the response of lung lesions and distant progression-free survival (DPFS) after radiosurgery in patients with brain metastases. A total of 47 consecutive patients were treated with radiosurgery for brain metastases. Distant progression was defined as a new enhancing intracranial tumor or leptomeningeal enhancement noted on follow-up magnetic resonance imaging. Progression of lung lesions was defined as follows: (1) a 20% increase in the summed diameter of the target lesions; (2) an absolute increase of 5 mm when the summed diameter was very small; or (3) detection of new lesions in the lung. Distant progression after radiosurgery was observed for twenty-one (44.7%) patients; we observed development of new distant metastases in nine patients, development of leptomeningeal seeding in eight patients, and combined failure of distant progression and local control failure in four patients. Forty-two (89.4%) patients had lung lesions at the time of radiosurgery, and progression of their lung lesions during the post-radiosurgery follow-up period was observed for 18 (38.3%) of these. The median DPFS was 7.00 months (95% CI, 6.153–7.847). Actuarial DPFS 3, 6, and 12 months after radiosurgery was 81.5, 61.3, and 36.7%, respectively. In multivariate analysis, only the criterion progression of lung lesions reached statistical and independent significance (P = 0.021, OR = 3.372, 95% CI, 1.200–9.480). The response of lung lesions after radiosurgery is likely to be a good predictor of DPFS after radiosurgery in patients with brain metastases.     

The treatment of recurrent brain metastases with stereotactic radiosurgery

Between May 1986 and August 1989, we treated 18 patients with 21 recurrent or persistent brain metastases with stereotactic radiosurgery using a modified linear accelerator. To be eligible for radiosurgery, patients had to have a performance status of greater than or equal to 70% and have no evidence of (or stable) systemic disease. All but one patient had received prior radiotherapy, and were treated with stereotactic radiosurgery at the time of recurrence. Polar lesions were treated only if the patient had undergone and failed previous complete surgical resection (10 patients). Single doses of radiation (900 to 2,500 cGy) were delivered to limited volumes (less than 27 cm3) using a modified 6MV linear accelerator. The most common histology of the metastatic lesion was carcinoma of the lung (seven patients), followed by carcinoma of the breast (four patients), and melanoma (four patients). With median follow-up of 9 months (range, 1 to 39), all tumors have been controlled in the radiosurgery field. Two patients failed in the immediate margin of the treated volume and were subsequently treated with surgery and implantation of 125I to control the disease. Radiographic response was dramatic and rapid in the patients with adenocarcinoma, while slight reduction and stabilization occurred in those patients with melanoma, renal cell carcinoma, and sarcoma. The majority of patients improved neurologically following treatment, and were able to be withdrawn from corticosteroid therapy. Complications were limited and transient in nature and no cases of symptomatic radiation necrosis occurred in any patient despite previous exposure to radiotherapy. Stereotactic radiosurgery is an effective and relatively safe treatment for recurrent solitary metastases and is an appealing technique for the initial management of deep-seated lesions as a boost to whole brain radiotherapy.     

Long-term survivors after gamma knife radiosurgery for brain metastases

BACKGROUND: Stereotactic radiosurgery, with or without whole-brain radiation therapy, has become a valued management choice for patients with brain metastases, although their median survival remains limited. In patients who receive successful extracranial cancer care, patients who have controlled intracranial disease are living longer. The authors evaluated all brain metastasis in patients who lived for > or = 4 years after radiosurgery to determine clinical and treatment patterns potentially responsible for their outcome. METHODS: Six hundred seventy-seven patients with brain metastases underwent 781 radiosurgery procedures between 1988 and 2000. Data from the entire series were reviewed; and, if patients had > or = 4 years of survival, then they were evaluated for information on brain and extracranial treatment, symptoms, imaging responses, need for further care, and management morbidity. These long-term survivors were compared with a cohort who lived for < 3 months after radiosurgery (n = 100 patients). RESULTS: Forty-four patients (6.5%) survived for > 4 years after radiosurgery (mean, 69 mos with 16 patients still alive). The mean age at radiosurgery was 53 years (maximum age, 72 yrs), and the median Karnofsky performance score (KPS) was 90. The lung (n = 15 patients), breast (n = 9 patients), kidney (n = 7 patients), and skin (melanoma; n = 6 patients) were the most frequent primary sites. Two or more organ sites outside the brain were involved in 18 patients (41%), the primary tumor plus lymph nodes were involved in 10 patients (23%), only the primary tumor was involved in 9 patients (20%), and only brain disease was involved in 7 patients (16%), indicating that extended survival was possible even in patients with multiorgan disease. Serial imaging of 133 tumors showed that 99 tumors were smaller (74%), 22 tumors were unchanged (17%), and 12 tumors were larger (9%). Four patients had a permanent neurologic deficit after brain tumor management, and six patients underwent a resection after radiosurgery. Compared with the patients who had limited survival (< 3 mos), long-term survivors had a higher initial KPS (P = 0.01), fewer brain metastases (P = 0.04), and less extracranial disease (P < 0.00005). CONCLUSIONS: Although the expected survival of patients with brain metastases may be limited, selected patients with effective intracranial and extracranial care for malignant disease can have prolonged, good-quality survival. The extent of extracranial disease at the time of radiosurgery was predictive of outcome, but this does not necessarily mean that patients cannot live for years if treatment is effective.     

Brain metastasis from prostate carcinoma: The M. D. Anderson Cancer Center experience

BACKGROUND: The objective of this study was to estimate the incidence and describe distribution, clinical presentation, and prognosis of brain metastases in patients with prostate carcinoma who were seen at The University of Texas M. D. Anderson Cancer Center (MDACC). METHODS: The authors reviewed the charts of 16,280 patients with prostate carcinoma in the MDACC patient data base. Of 131 patients with craniospinal metastases confirmed by neuroimaging (n=53 patients) or autopsy (n=78 patients), 103 of 16,280 patients (0.63%) had parenchymal metastases. RESULTS: The median patient age at diagnosis was 64 years (range, 16-85 years). The median interval from the diagnosis of prostate carcinoma to the detection of brain metastasis was 35 months for patients with adenocarcinoma and 48 months for patients with small cell carcinoma (SCC). Confusion, headache, and memory deficits were the most frequent initial symptoms. Eighty-six percent of patients had single lesions, and 14% of patients had > or = 2 lesions. Metastases were supratentorial in 81 of 103 patients (76%), infratentorial in 22 of 103 patients (21%), and both supratentorial and infratentorial in 3 of 103 patients (3%). SCC and cribriform subtypes were more likely than adenocarcinoma to metastasize to the brain (relative risk, 20.36; 95% confidence interval, 9.91-41.84). Regardless of histology, the median survival in untreated patients was 1 month compared with 3.5 months in patients who were treated with radiotherapy. Patients who underwent stereotactic radiosurgery (n=5 patients) had a longer median survival (9 months). Survival was not affected by supratentorial or infratentorial location of metastases. CONCLUSIONS: Brain metastasis from prostate carcinoma is a rare, terminal event with death in <1 year frequently due to advanced, systemic disease. The majority of metastases were single and supratentorial. The most common clinical presentation was nonfocal neurologic symptoms related to intracranial hypertension. A better understanding of the biology of prostate carcinoma will help clarify the basis for its metastasis to the brain.     

立体定向伽玛刀放射外科治疗肺癌脑转移瘤的疗效分析

目的:探讨伽玛刀治疗肺癌脑转移瘤的临床疗效及不良反应。方法:选择伽玛刀治疗肺癌脑转移瘤患者236 例,根据病变大小和部位选用4-18mm 准直器靶点,肿瘤边缘剂量12-22Gy,平均17Gy,中心剂量32-40Gy,平均35.4Gy,边缘等剂量曲线40%-75％,平均58％。 结果:对全部患者伽玛刀治疗后进行临床随访,视具体情况1-3 个月复查影像,随访时限不少于半年;6个月、12个月患者生存率,腺癌患者分别为69.1％（56/81）、38.3％（31/81）,鳞癌患者为60.0％（45/75）、20.0％（15/75）,小细胞癌患者则为62.7％（37/59）、27.1％（16/59）;伽玛刀治疗后1-3个月随访KPS评分,提高128 例（54.2％）,不变81 例（34.3％）,下降27例（11.4％）。腺癌、鳞癌、小细胞癌、鳞腺混合癌脑转移瘤局部控制有效率分别为87.7％（71/81）、93.3％（70/75）、100％（59/59）、85.7％（18/21）。无1例患者出现严重脑水肿而终止放疗,无1例患者出现严重骨髓功能抑制。 结论:伽玛刀治疗肺癌脑转移瘤具有疗效好、安全的优势,能有效提高脑转移瘤患者生活质量,延长生存期。     

The role of whole brain radiotherapy and stereotactic radiosurgery on brain metastases from renal cell carcinoma

PURPOSE: We reviewed our experience with patients who have undergone stereotactic radiosurgery (SRS) for brain metastases secondary to renal cell carcinoma (RCC). Analysis was performed to determine the survival, local control, distant brain failure (DBF), and then to define which tumors may not require upfront whole-brain radiotherapy (WBRT). METHODS AND MATERIALS: Twenty-nine patients with 66 tumors underwent SRS from 1991 to 1998. Median follow-up from time of brain metastases diagnoses relative to each tumor was 12.5 months and 6.8 months from the time of SRS. Median SRS dose was 1,800 cGy to the 60% isodose line. Three patients had undergone SRS for previously treated tumors. RESULTS: Median survival time from diagnosis was 10.0 months. Overall survival was not affected by age, addition of WBRT, number of lesions, tumor volume, or the presence of systemic disease. Of the 23 patients with follow-up neuroimaging, 4 of 47 (9%) tumors recurred. The addition of WBRT did not improve local control. Of the 13 patients who presented with a single lesion, 3 went on to develop DBF (23%), while 6 of the 10 patients who presented with multiple metastases developed DBF (60%). CONCLUSION: Patients with brain metastases secondary to RCC treated by SRS alone have excellent local control. The decision of whether or not to add WBRT to SRS should depend on whether the patient has a high likelihood of developing DBF. Our study suggests that patients who present with multiple brain lesions may be more likely to benefit from the addition of WBRT because they appear to be more than twice as likely to develop DBF as compared to patients with a single lesion.     

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.     

Local control after fractionated stereotactic radiation therapy for brain metastases

Stereotactic radiosurgery (SRS) is frequently used in the management of brain metastases, but concerns over potential toxicity limit applications for larger lesions or those in eloquent areas. Fractionated stereotactic radiation therapy (SRT) is often substituted for SRS in these cases. We retrospectively analyzed the efficacy and toxicity outcomes of patients who received SRT at our institution. Seventy patients with brain metastases treated with SRT from 2006–2012 were analyzed. The rates of local and distant intracranial progression, overall survival, acute toxicity, and radionecrosis were determined. The SRT regimen was 25 Gy in 5 fractions among 87 % of patients. The most common tumor histologies were non-small cell lung cancer (37 %), breast cancer (20 %) and melanoma (20 %), and the median tumor diameter was 1.7 cm (range 0.4–6.4 cm). Median survival after SRT was 10.7 months. Median time to local progression was 17 months, with a local control rate of 68 % at 6 months and 56 % at 1 year. Acute toxicity was seen in 11 patients (16 %), mostly grade 1 or 2 with the most common symptom being mild headache. Symptomatic radiation-induced treatment change was seen on follow-up MRIs in three patients (4.3 %). SRT appears to be a safe and reasonably effective technique to treat brain metastases deemed less suitable for SRS, though dose intensification strategies may further improve local control.     

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.     

Patient selection criteria for the treatment of brain metastases with stereotactic radiosurgery

In this study we evaluate prognostic factors that predict local-regional control and survival following stereotactic radiosurgery (SRS) in patients with brain metastasis and establish guidelines for patient selection. Our evaluation is based on 73 patients with brain metastasis treated with SRS at the University of Minnesota between March 1991 and November 1995. The ability of stereotactic radiosurgery to improve local control in patients with brain metastases is confirmed in our study in which only 6 of 62 patients failed locally after SRS, with an actuarial local progression-free survival of 80% at 2 years. Variables that predicted worse prognosis were larger tumor size (p=0.05) for local progression-free survival and multiplicity of metastasis (p=0.03) and infratentiorial location of metastases (p=0.006) for regional progression-free survival. Absence of extracranial disease, KPS 70, and single intracranial metastasis were significant predictors of longer survival. Patients who fulfill all three criteria will survive longer after SRS (MS=17.7 months) and will most likely benefit from the increase local control in the brain achieved by SRS. Survival in patients who do not meet any of these criteria is very poor (MS=1.5 months), and these patients are less likely to benefit from this treatment. Careful selection of patients for SRS is warranted.     

Radiosurgery for solitary brain metastases using the cobalt-60 gamma unit: methods and results in 24 patients.

To define the role of stereotactic radiosurgery in the treatment of metastatic brain tumors we treated 24 consecutive patients (20 men, 4 women) with the 201-source 60Co gamma unit between May 1988 and March 1990. The primary tumors included malignant melanoma (n = 10), non-small cell lung carcinoma (n = 6), renal cell carcinoma (n = 3), colorectal carcinoma (n = 1), oropharyngeal carcinoma (n = 1), and adenocarcinoma of unknown origin (n = 3). All tumors were less than or equal to 3.0 cm in greatest diameter. Twenty patients received a planned combination of 30-40 Gy whole brain fractionated irradiation and a radiosurgical "boost" of 16-20 Gy to the tumor margins; one patient refused conventional fractionated irradiation. Three patients with recurrent, persistent, or new non-small cell lung carcinomas had radiosurgical treatment 12-20 months after receiving 30-42.5 Gy whole-brain external beam irradiation. Stereotactic computed tomographic imaging was used for target coordinate determination and imaging-integrated dose planning. All tumors were enclosed by the 50-90% isodose shell using one (n = 22), two (n = 1), or three (n = 1) irradiation isocenters. During this 23-month period (median follow-up of 7 months) no patient died from progression of a radiosurgically-treated brain metastasis. Ten patients died of systemic disease (n = 8) or remote central nervous system metastasis (n = 2) between 1 week and 10 months after radiosurgery. One patient had tumor progression and underwent craniotomy and tumor excision 5 months after radiosurgery. To date, median survival after radiosurgery has been 10 months; 1-year survival was 33.3%. Stereotactic radiosurgery eliminated the surgical and anesthetic risks associated with craniotomy and resection of solitary brain metastases. Radiosurgery also effectively controlled the growth of tumors considered "resistant" to conventional irradiation.     

First treatment for brain metastases by stereotactic radiosurgery]

Local control of brain metastases is better with first treatment by stereotactic radiosurgery than with radiosurgery for recurrence. We reported a retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery realised in first intention. From January 1994 to December 1997, 26 patients presenting with 43 metastases underwent radiosurgery. The median age was 61 years and the median Karnofsky index 70. Primary sites included: lung (12 patients), kidney (7 patients), breast (2 patients), colon (1 patient), melanoma (2 patients), osteosarcoma (1 patient), it was unknown for one patient. Seven patients had extracranial metastases. Twenty-one sessions of radiosurgery have been realized for one metastase, and 9 for two, three or four lesions. The median diameter was 21 mm and the median volume 1.8 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. Forty-two metastases were evaluable for response analysis. The overall local control rate was 90.5% and the 1-year, 2- and 3-year actuarial rates were 85% and 75%. In univariate analysis, theorical radioresistance was significantly associated with better local control (100% versus 77%, p < 0.05). All patients were evaluable for survival. The median survival rate was 15 months. Four patients had a symptomatic oedema (RTOG grade II). Two lesions have required a surgical excision. In conclusion, low dose radiosurgery (14 Gy delivered at the periphery of metastasis) can be proposed in first intention for brain metastases, in particularly for theorical radioresistant lesions.     

Stereotactic irradiation using a linear accelerator for brain metastasis from renal cell carcinoma

Background The role of stereotactic irradiation using a linear accelerator for brain metastasis from renal cell carcinoma was investigated. Methods Fifteen brain metastases in 11 patients with a history of renal cell carcinoma were treated using convergent narrow x-ray beams from a linear accelerator and rigid fixation of the head with a stereotactic frame. Twelve metastatic tumors in8 patients were irradiated with 25 Gy at the center in a single fraction, and single tumors in 3 patients received the following doses: 25 Gy in 5 fractions, 28 Gy in 3 fractions, or 35 Gy in 4 fractions Results The actuarial local control rate at 12 months was 90.6%. Twelve (92%) of 13 lesions that produced neurologic symptoms before stereotactic irradiation showed an improvement of symptoms. No complication related to the irradiation was observed. The median survival time was 6 months. Conclusion Stereotactic irradiation is more effective in achieving local control than is conventional radiotherapy, and achieves improvement in symptoms and survival rates similar to those of surgical resection of the brain metastasis from renal cell carcinoma. Urologists and oncologists should be aware of the usefulness of stereotactic radiation in the management of patients with renal cell carcinoma.