LINAC radiosurgery for brain metastasis of renal cell carcinoma

The purpose of the study was to evaluate the efficacy and toxicity of stereotactic radiotherapy in the treatment of the brain metastasis of renal cell carcinoma. From 1994 to 2001, 28 patients presenting with 65 metastases of renal cell cancer were treated by radiosurgery. Median age was 55 years (35-75), and median Karnofski performance status ranges between 50 and 100. Seven patients had received whole brain radiotherapy (WBRT) before radiosurgery. Twelve patients were treated by radiosurgery for 1 metastasis, 5 patients for two metastases and 6 for three, and 5 for more than three metastases. One procedure was performed in 22 patients and, 2 or 3 procedures for 6 patients. Median metastasis diameter was 19 mm (5-55 mm). Median metastasis volume was 1.28 cc (0.02-28 cc). Irradiation was delivered by linear accelerator. Median minimal dose (on the 70% isodose) was 14.7 Gy (10.8 Gy, 19.5 Gy), median maximal dose (at the isocenter) 20.5 Gy (14.3 Gy, 39.6 Gy). Median follow-up was 14 months (1-33). Two metastases progressed (3%), 2 and 12 months after radiosurgery. Overall, crude local control rate was 97% and 3-, 6- and 12-month local control rates were 98% +/- 2%, 98% +/- 2%, and 93% +/- 5%, respectively. In univariate analysis, no prognostic factor of local control was retrieved. Median brain disease-free survival was 25 months after RS. the 3-, 6- and 12-month distant brain control rates were 91% +/- 4%, 91% +/- 4%, and 70% +/- 12%, respectively. Median survival duration was 11 months. The 3-, 6-, 12- and 24-month overall survival rates were 82% +/- 7%, 67% +/- 9%, 48% +/- 10%, and 33% +/- 10%, respectively. According to univariate analysis, only site of metastasis was overall survival prognostic factor. Radiosurgery for brain metastasis of renal cell carcinoma is an effective and accurate treatment. The use of radiosurgery alone is an appropriate management strategy for many patients with brain metastasis of renal cell carcinoma. Radiosurgery is efficient even after development of new metastasis appearing after WBRT.     

Stereotactic radiosurgery for brainstem metastases.

OBJECT: Brainstem metastases portend a dismal prognosis. Surgical resection is not part of routine management and radiation therapy has offered little clinical benefit. Radiosurgery provides a safe and effective treatment for many patients with brain metastasis, but its role in the brainstem has not been evaluated. In this study the authors examine the role of radiosurgery in the treatment of brainstem metastases. METHODS: The authors reviewed the outcomes after stereotactic radiosurgery in 26 patients with 27 brainstem metastases. Tumor locations included the pons (21 tumors) and midbrain (six tumors): 14 patients had additional tumors in other locations. Twenty patients presented with brainstem signs. The median dose to the tumor margin was 16 Gy (range 12-20 Gy). Twenty-four patients received fractionated whole-brain radiation therapy (WBRT) and 12 underwent additional chemotherapy or immunotherapy. The median follow-up time in these patients was 9.5 months (range 1-43 months). After radiosurgery, the local control rate in brainstem tumors was 95%. In one patient in whom the tumor initially decreased in size, tumor enlargement was seen 7 months later. The median survival time was 11 months after diagnosis and 9 months after radiosurgery. Thirteen patients improved, 10 were stable, and three deteriorated. Eventually, 22 patients died, 18 of progression of their extracranial disease, three of new tumor growth (including one hemorrhage into a new brain metastasis), and one of extracranial disease plus new brain tumor growth. CONCLUSIONS: Although they have slightly lower than the expected survival rates of patients with nonbrainstem tumors, patients with brainstem metastases may achieve effective palliation after stereotactic radiosurgery and WBRT.     

The role of cyberknife radiosurgery/radiotherapy for brain metastases of multiple or large-size tumors.

OBJECTIVE: Focused, highly targeted radiosurgery and fractionated radiotherapy using the Cyberknife are useful treatments for multiple or large metastases. Here we present our results of Cyberknife radiosurgery for 71 patients with 148 metastatic brain lesions. METHODS: There were 32 women and 39 men with a median age of 63 (range: 30-88) years. Radiographic follow-up was available for 60 patients with 104 lesions. The mean and median initial volumes of the tumor per lesion were 6.6 and 2.9 cm(3) (range: 0.1-53.2 cm(3)), respectively, at the time of the initial Cyberknife treatment. Forty patients (56%) had a single lesion, and 31 (44%) had multiple lesions (range: 2-7) at initial treatment. The number of fractions ranged from 1 to 3, and forty (27%) of 148 lesions were treated by a fractionated course of Cyberknife therapy. The mean marginal dose was 20.2 Gy (range 7.8-30.1 Gy, median: 20.7 Gy). RESULTS: At 44 weeks of median follow-up, there were no permanent symptoms resulting from radiation necrosis. Overall 6-month and 1-year survival rates were 74% and 47%, respectively, and the median survival time was 56 weeks. The Karnofsky performance score and extracranial metastasis were significant prognostic factors at 6 months and 1 year, respectively, in both univariate and multivariate analyses. Age or multiple metastases did not influence prognosis at 6 months and 1 year. Local control was achieved in 83% (86 lesions). After additional radiosurgical or surgical salvage, no patient died as a result of intracranial disease. Twenty-five patients developed 92 new metastases (range 1-13) outside of the treated lesions with 22.4 weeks of median follow-up. Among them, 21 patients (84 lesions) were treated by salvage Cyberknife. CONCLUSION: Despite the inclusion of an unfavorable group of patients with large tumors, our results for survival and tumor control rates are comparable to those of published series. The Cyberknife provides the advantage of allowing for fractionated treatment to multiple or large-size tumors.     

Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy?

OBJECTIVE: Whole brain radiotherapy (WBRT) provides benefit for patients with brain metastases but may result in neurological toxicity for patients with extended survival times. Stereotactic radiosurgery in combination with WBRT has become an important approach, but the value of WBRT has been questioned. As an alternative to WBRT, we managed patients with stereotactic radiosurgery alone, evaluated patients' outcomes, and assessed prognostic factors for survival and tumor control. METHODS: One hundred seventy-two patients with brain metastases were managed with radiosurgery alone. One hundred twenty-one patients were evaluable with follow-up imaging after radiosurgery. The median patient age was 60.5 years (age range, 16-86 yr). The mean marginal tumor dose and volume were 18.5 Gy (range, 11-22 Gy) and 4.4 ml (range, 0.1-24.9 ml). Eighty percent of patients had solitary tumors. RESULTS: The overall median survival time was 8 months. The median survival time in patients with no evidence of primary tumor disease or stable disease was 13 and 11 months. The local tumor control rate was 87%. At 2 years, the rate of local control, remote brain control, and total intracranial control were 75, 41, and 27%, respectively. In multivariate analysis, advanced primary tumor status (P = 0.0003), older age (P = 0.008), lower Karnofsky Performance Scale score (P = 0.01), and malignant melanoma (P = 0.005) were significant for poorer survival. The median survival time was 28 months for patients younger than 60 years of age, with Karnofsky Performance Scale score of at least 90, and whose primary tumor status showed either no evidence of disease or stable disease. Tumor volume (P = 0.02) alone was significant for local tumor control, whereas no factor affected remote or intracranial tumor control. Eleven patients developed complications, six of which were persistent. Nineteen (16.5%) of 116 patients in whom the cause of death was obtained died as a result of causes related to brain metastasis. CONCLUSION: Brain metastases were controlled well with radiosurgery alone as initial therapy. We advocate that WBRT should not be part of the initial treatment protocol for selected patients with one or two tumors with good control of their primary cancer, better Karnofsky Performance Scale score, and younger age, all of which are predictors of longer survival.     

LINAC Radiosurgery for Patients with a Limited Number of Brain Metastases

Patients (pts) with brain metastases have a high risk of cancer-related death due to extra- or intracranial tumor manifestations. The present retrospective analysis demonstrates the ability of linear accelerator (LINAC)-based radiosurgery to control intracranial disease and prolong survival in pts with one to three metastases. From 1991 to 1996, 106 pts (42 females, 64 males; median age, 57 years) with cerebral metastases were treated by stereotactic radiosurgery with a LINAC (8 MeV) equipped with tertiary collimators. In 70 pts, a single metastasis was present; 36 pts had two or three metastases. Fifty-nine pts were treated for their first occurrence of brain metastases; 47 pts had been treated prior to radiosurgery by resection and/or whole-brain irradiation. Histology of the primary tumor was non–small cell lung cancer (36 pts), melanoma (20 pts), breast cancer (15 pts), hypernephroma (15 pts), and other (20 pts). All together, 157 metastases (0.04–69.0 ml; median, 2.7 ml) were irradiated with marginal doses of 12–25 Gy (median, 20 Gy) referred to the 65–80% isodose. Seventy-two percent of the lesions were treated with a single isocenter. Adjuvant whole-brain irradiation was applied in six pts. One hundred thirty-five of 157 metastases were evaluated for response: complete response (CR), 24%; partial response, 31%; no change, 30%; and progression of disease, 15%. CR rates were highest (48%) in small metastases (<1-cm diameter), independent of histological type and dose. The overall median survival was 8 months. Multivariate Cox regression analysis revealed a significant impact on survival for Karnofsky performance score, presence of extracranial tumor, and volume of largest metastasis. Freedom from neurological death was determined only by the volume of the largest metastasis. Patients with multiple metastases and/or extracranial disease had a higher risk of developing new outfield brain metastases. Due to salvage therapy (second or third course of stereotactic radiosurgery, whole-brain irradiation, surgery), the overall survival in pts with two or three metastases did not significantly differ from that in pts with single metastases. LINAC-based stereotactic radiosurgery in pts with up to three cerebral metastases results in survival rates approaching those of pts with resected single brain metastases. As pts with both single and multiple metastases can effectively be salvaged after receiving radiosurgery, extracranial tumor activity becomes a major determinator of survival.     

Boost radiosurgery for treatment of brain metastases after surgical resections

BACKGROUND: We evaluated results of resection surgery followed by boost radiosurgery for the treatment of brain metastases. METHODS: We treated 21 patients (13 male, 8 female) with surgical resection (subtotal or total) followed by boost radiosurgery. The mean patient age was 61 years (range, 41-80 years); supratentorial lesions were treated in 12 patients, and posterior fossa lesions were treated in 9 patients. The most common primary cancers were lung (24%) and colon (24%). Fifty-three percent of patients had brain metastases only, whereas 47% had extracranial metastases. The radiosurgery dose plan was designed to radiate the operative cavity; the mean treatment volume (50% isodose) was 10.7 mL (range, 3.4-23.3 mL), and the mean marginal dose was 17 Gy (range, 13-20 Gy). RESULTS: Local control was achieved in 16 (76%) patients. However, new intracranial lesions developed in 10 patients, and meningeal carcinomatosis occurred in 5 patients. Local tumor recurrence occurred more often for patients treated with lower radiotherapy doses (<18 vs > or =18 Gy, P = .03), and meningeal carcinomatosis occurred more often in patients with posterior fossa lesions (P = 0.05). Gamma knife radiosurgery was performed in 13 patients, and whole-brain radiation was performed in 2 patients. No patients experienced symptomatic radiation injury, and the median survival time was 20 months. CONCLUSIONS: Although boost radiosurgery is less invasive and reduces morbidity, the radiosurgical dose must be higher than 18 Gy for the treatment to be most effective. Treatment of lesions of the posterior fossa must be considered carefully because of the higher frequency of meningeal carcinomatosis. Also, we recommend that the surgeons who operate on the metastatic tumors must try to decrease the resected cavity volume and to prevent cerebrospinal fluid dissemination at the operation for posterior fossa lesions.     

Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control

OBJECT: Renal cell carcinoma is a leading cause of death from cancer and its incidence is increasing. In many patients with renal cell cancer, metastasis to the brain develops at some time during the course of the disease. Corticosteroid therapy, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, the median survival in patients with renal cell carcinoma metastasis is approximately 3 to 6 months. In this study the authors examined the efficacy of gamma knife surgery in treating renal cell carcinoma metastases to the brain and evaluated factors affecting long-term survival. METHODS: The authors conducted a retrospective review of 69 patients undergoing stereotactic radiosurgery for a total of 146 renal cell cancer metastases. Clinical and radiographic data encompassing a 14-year treatment interval were collected. Multivariate analyses were used to determine significant prognostic factors influencing survival. The overall median length of survival was 15 months (range 1-65 months) from the diagnosis of brain metastasis. After radiosurgery, the median survival was 13 months in patients without and 5 months in those with active extracranial disease. In a multivariate analysis, factors significantly affecting the rate of survival included the following: 1) younger patient age (p = 0.0076); 2) preoperative Karnofsky Performance Scale score (p = 0.0012); 3) time from initial cancer diagnosis to brain metastasis diagnosis (p = 0.0017); 4) treatment dose to the tumor margin (p = 0.0252); 5) maximal treatment dose (p = 0.0127); and 6) treatment isodose (p = 0.0354). Prior tumor resection, chemotherapy, immunotherapy, or whole-brain radiation therapy did not correlate with extended survival. Postradiosurgical imaging of the brain demonstrated that 63% of the metastases had decreased, 33% remained stable, and 4% eventually increased in size. Two patients (2.9%) later underwent a craniotomy and resection for a tumor refractory to radiosurgery or a new symptomatic metastasis. Eighty-three percent of patients died of progression of extracranial disease. CONCLUSIONS: Stereotactic radiosurgery for treatment of renal cell carcinoma metastases to the brain provides effective local tumor control in approximately 96% of patients and a median length of survival of 15 months. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can offer patients an extended survival.     

大肠癌脑转移的临床特征及其手术治疗

目的 分析大肠癌脑转移的临床特征及其手术治疗转归. 方法回顾性分析手术治疗的大肠癌伴脑转移28例患者的临床资料,统计数据采用单因素Log-Rank分析和多因素Cox回归分析法.结果 大肠癌继发脑转移的中位年龄为57(41～75)岁,原发肿瘤与转移瘤间隔的中位时间为13.5个月,其中合并颅外(肺、肝、骨)转移占61%(17/28),仅有脑转移的占39%(11/28).脑转移瘤主要表现为头痛、呕吐等颅内压升高征候群和偏瘫、下肢乏力、失语等定位症状以及癫痫等,颅内转移瘤以单发病灶为多见,占82%(23/28),位于幕上(枕叶、顶叶、额叶)者占57%(16/28),位于幕下(小脑)者占43%(12/28);转移性脑瘤手术切除后中位生存时间为9.4个月,1年生存率为28.9%,5年生存率为7.1%.多因素分析提示颅内单发病灶转移(χ2=7.35,P<0.05)和无颅外其他部位转移(χ2=6.47,P<0.05)是大肠癌脑转移预后的独立影响因素.28例均接受手术切除和多学科协作治疗,无手术死亡和出血及再手术病例.结论 大肠癌脑转移总体预后欠佳,手术切除脑转移病灶可延长部分患者的存活时间.     

大肠癌脑转移的临床特征及其手术治疗

目的 分析大肠癌脑转移的临床特征及其手术治疗转归. 方法回顾性分析手术治疗的大肠癌伴脑转移28例患者的临床资料,统计数据采用单因素Log-Rank分析和多因素Cox回归分析法.结果 大肠癌继发脑转移的中位年龄为57(41～75)岁,原发肿瘤与转移瘤间隔的中位时间为13.5个月,其中合并颅外(肺、肝、骨)转移占61%(17/28),仅有脑转移的占39%(11/28).脑转移瘤主要表现为头痛、呕吐等颅内压升高征候群和偏瘫、下肢乏力、失语等定位症状以及癫痫等,颅内转移瘤以单发病灶为多见,占82%(23/28),位于幕上(枕叶、顶叶、额叶)者占57%(16/28),位于幕下(小脑)者占43%(12/28);转移性脑瘤手术切除后中位生存时间为9.4个月,1年生存率为28.9%,5年生存率为7.1%.多因素分析提示颅内单发病灶转移(χ2=7.35,P<0.05)和无颅外其他部位转移(χ2=6.47,P<0.05)是大肠癌脑转移预后的独立影响因素.28例均接受手术切除和多学科协作治疗,无手术死亡和出血及再手术病例.结论 大肠癌脑转移总体预后欠佳,手术切除脑转移病灶可延长部分患者的存活时间.     

大肠癌脑转移的临床特征及其手术治疗

目的 分析大肠癌脑转移的临床特征及其手术治疗转归. 方法回顾性分析手术治疗的大肠癌伴脑转移28例患者的临床资料,统计数据采用单因素Log-Rank分析和多因素Cox回归分析法.结果 大肠癌继发脑转移的中位年龄为57(41～75)岁,原发肿瘤与转移瘤间隔的中位时间为13.5个月,其中合并颅外(肺、肝、骨)转移占61%(17/28),仅有脑转移的占39%(11/28).脑转移瘤主要表现为头痛、呕吐等颅内压升高征候群和偏瘫、下肢乏力、失语等定位症状以及癫痫等,颅内转移瘤以单发病灶为多见,占82%(23/28),位于幕上(枕叶、顶叶、额叶)者占57%(16/28),位于幕下(小脑)者占43%(12/28);转移性脑瘤手术切除后中位生存时间为9.4个月,1年生存率为28.9%,5年生存率为7.1%.多因素分析提示颅内单发病灶转移(χ2=7.35,P<0.05)和无颅外其他部位转移(χ2=6.47,P<0.05)是大肠癌脑转移预后的独立影响因素.28例均接受手术切除和多学科协作治疗,无手术死亡和出血及再手术病例.结论 大肠癌脑转移总体预后欠佳,手术切除脑转移病灶可延长部分患者的存活时间.     

Adjuvant stereotactic radiosurgery for anaplastic ependymoma

OBJECT: The purpose of this retrospective study is to evaluate the role of stereotactic radiosurgery using the Gamma Knife as an adjuvant to other modalities used in the treatment of malignant ependymomas of both children and adults and to assess its efficacy in terms of tumor control and overall survival. METHOD: Between 1987 and 1998, 22 patients in the age range of 1.5-65 years (mean age 22. 3) with progressive anaplastic ependymoma were treated by stereotactic radiosurgery using the 201 source Co-60 Leksell Gamma Knife at the University of Pittsburgh. The irradiated tumor volume varied from 0.84 to 36.8 cm(3) (mean 13.7). The median dose delivered to the tumor margin was 16.1 Gy (range 10-20), and the mean maximal dose was 32.2 Gy (range 20-40). The disease-free survival, the tumor control rate and the overall survival were recorded to evaluate the efficacy of radiosurgery. The median follow-up from radiosurgery was 21 months (range 4-84). RESULTS: Median survival after radiosurgery was 2.2 years (46.6 +/- 12.1% 5-year actuarial). Median survival from the initial diagnosis was 10. 1 years (50.3 +/- 12.5% at 5 years, 37.7 +/- 14.4% at 10 years). Reduction or stabilization of the treated tumor was seen in 16 out of 22 (68%) patients. Forty-one percent of the patients eventually developed delayed distant cerebral recurrence outside the treated volume. The 5-year actuarial rates for local control and cranial control at any location were 62.3 +/- 13.6% and 32.4 +/- 10.8%, respectively. No complication occurred as a side effect of radiosurgery. CONCLUSION: For patients with locally recurrent or progressive anaplastic ependymomas, Gamma Knife stereotactic radiosurgery proved to be safe and effective as a salvage adjuvant therapy to achieve local tumor control and improve survival.     

Stereotactic radiosurgery for patients with "radioresistant" brain metastases

OBJECTIVE: Our aim was to evaluate the efficacy of stereotactic radiosurgery (SRS) for the treatment of patients with brain metastases that have been determined to be "radioresistant" on the basis of histological examination. METHODS: We reviewed the medical records of 41 consecutive patients who presented with 83 brain metastases from radioresistant primaries and subsequently underwent SRS. All patients were followed until death or for a median of 31 months after SRS. Tumor histologies included renal cell carcinoma (16 patients), melanoma (23 patients), and sarcoma (2 patients). Eighteen patients (44%) had a solitary metastasis, and 23 patients (56%) had multiple metastases. RESULTS: The median overall survival time was 14.2 months after SRS. On the basis of univariate analysis, systemic disease status (P = 0.006) and Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (P = 0.005) were associated with survival. The median survival time was 23.5 months for patients in RPA Class I status and 10.5 months for patients in RPA Class II or III status. There was a trend (P = 0.12) toward improved median survival for patients with renal cell carcinoma (17.8 mo) as compared with patients with melanoma (9.7 mo). Multivariate analysis showed RPA class (P = 0.038) and histological diagnosis of primary tumor (P < 0.001) to be independent predictors for overall survival. In the 35 patients who underwent follow-up imaging, 9 (12%) of 73 tumors recurred locally. In 54% of the patients, distant brain failure (DBF) developed. Whole brain radiotherapy (WBRT) improved local control and decreased DBF, according to the univariate and multivariate analyses. Patients who received adjuvant WBRT in addition to SRS had 6-month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Patients who received adjuvant WBRT with SRS had a 6-month actuarial DBF rate of 17%, as compared with a rate of 64% among patients who had SRS alone (P = 0.0027). CONCLUSION: Well-selected patients with brain metastases from radioresistant primary tumors who undergo SRS survive longer than historical controls. RPA Class I status and primary renal cell carcinoma predict longer survival. Adjuvant WBRT improves local control and decreases DBF but does not affect overall survival. Further studies are needed to determine which patients should receive WBRT.     

Repeated gamma knife surgery for multiple brain metastases from renal cell carcinoma

OBJECT: The aim of this study was to evaluate the therapeutic profile of repeated gamma knife surgery (GKS) for renal cell carcinoma that has metastasized to the brain on multiple occasions. METHODS: Data from this study were culled from a single institution and cover a 6-year period of outpatient radiosurgery. A standard protocol for indication, dose planning, and follow up was established. In cases of distant or local recurrences, radiosurgery was undertaken repeatedly (up to six times in one individual). Seventy-five patients harboring 350 cerebral metastases were treated. Relief from pretreatment neurological symptoms occurred in 72% of patients within a few days or a few weeks after the procedure. The actuarial local tumor control rate after the initial GKS was 95%. In patients free from relapse of intracranial metastases after repeated radiosurgery, long-term survival was 91% after 4 years; median survival was 11.1+/-3.2 months after radiosurgery and 4.5+/-1.1 years after diagnosis of the primary kidney cancer. Survival following radiosurgery was independent of patient age and sex, side of the renal cell carcinoma, pretreatment of the cerebrum by using radiotherapy or surgery, number of brain metastases and their synchronization with the primary renal cell carcinoma, and the frequency of radiosurgical procedures. In contrast, survival was dependent on the patient's clinical performance score and the extracranial tumor status. Tumor bleeding was observed in seven patients (9%) and late radiation toxicity (LRT) in 15 patients (20%). Treatment-related morbidity was moderate and mostly transient. Late radiation toxicity was encountered predominantly in long-term survivors. CONCLUSIONS: Outpatient repeated radiosurgery is an effective and only minimally invasive treatment for multiple brain metastases from renal cell cancer and is recommended as being the method of choice to control intracranial disease, especially in selected patients with limited extracranial disease. Physicians dealing with such patients should be aware of the characteristic aspects of LRT.     

Prognostic factors in patients treated with stereotactic image-guided robotic radiosurgery for brain metastases: a single-center retrospective analysis of 223 patients

In this retrospective study, we evaluated the overall survival (OS) and local control (LC) of brain metastases (BM) in patients treated with stereotactic radiosurgery (SRS). The scope was to identify host, tumor, and treatment factors predictive of LC and survival and define implications for clinical decisions. A total of 223 patients with 360 BM from various histologies treated with SRS alone or associated with whole brain radiotherapy (WBRT) in our institution between July 1, 2008 and August 31, 2013 were retrospectively reviewed. Among other prognostic factors, we had also evaluated retrospectively Karnofsky performance status scores (KPS) and graded prognostic assessment (GPA). Overall survival (OS) and local control (LC) were the primary endpoints. Kaplan-Meier and Cox proportional hazards models were used to estimate OS and LC and identify factors predictive of survival and local control. The median duration of follow-up time was 9 months (range 0.4–51 months). Median overall survival of all patients was 11 months. The median local control was 38 months. No statistical difference in terms of survival or LC between patients treated with SRS alone or associated with WBRT was found. On multivariate analysis, KPS was the only statistically significant predictor of OS (hazard ratio [HR] 2.53, p?=?0.006). On univariate analysis, KPS and GPA were significantly prognostic for survival. None of the host, tumor, or treatment factors analyzed in the univariate model factors were significantly associated with local failure.     

Radiosurgery to palliate symptoms in brain metastases from uterine cervix cancer

Background

The optimal management of brain metastases from uterine cervix cancer (UCC) is not well defined because of the rarity of the condition and the scarcity of published reports. Here we report our experience with stereotactic radiosurgery for the management of brain metastases from UCC.

Methods

Thirteen consecutive patients with brain metastases from UCC were managed with a Leksell gamma-knife at our institution between January 2003 and December 2010. Clinical features and radiosurgical outcomes of patients were analyzed retrospectively.

Results

Gamma-knife radiosurgery (GKRS) was chosen as the only treatment in four patients and performed in combination with whole-brain radiotherapy (WBRT) in nine patients. GKRS was conducted simultaneously with WBRT within a 1-month interval in six patients and was chosen as the salvage treatment after WBRT in three patients. The mean number of metastatic brain lesions per patient was 5.7 (range, 1–16). The median cumulative tumor volume was 23.7 cm³ (range, 2.7–40.2 cm³), and the median marginal dose covering the tumors was 14 Gy of a 50 % isodose line (range, 8–25 Gy). Nine patients showed relief of main neurologic symptoms after GKRS. The median length of time that the patients spent in an improved neurologic state was 11.1 weeks (range, 2–39.6 weeks). The local and distant control rates were 66.7 % and 77.8 %, respectively. The median survival from the date of GKRS until death was 4.6 months (range, 1.0–15.9 months). The 6-month and 12-month survival rates after GKRS were 38 and 15 %, respectively.

Conclusions

GKRS could be an efficient palliative measure to relieve neurologic symptoms caused by brain metastasis from UCC.     

Surgical resection for metastatic melanoma to the liver: the John Wayne Cancer Institute and Sydney Melanoma Unit experience

HYPOTHESIS: Metastatic melanoma to the liver is not incurable; complete surgical resection can achieve long-term survival in selected patients. BACKGROUND: Metastases to the liver are diagnosed in 10% to 20% of patients with American Joint Committee on Cancer stage IV melanoma. Surgical resection has not been generally accepted as a therapeutic option, as most patients will have other sites of disease that limit their survival to a median of only 4 to 6 months. However, there is little information on outcomes following resection in those patients with disease limited to the liver. PATIENTS AND METHODS: Review of the prospective melanoma databases at the John Wayne Cancer Institute, Santa Monica, Calif, and the Sydney Melanoma Unit, Sydney, Australia, identified 1750 patients with hepatic metastases, of whom 34 (2%) underwent exploration with intent to resect the metastases. Prognostic factors within the group of patients who underwent resection were examined by univariate and multivariate analysis, and median disease-free survival (DFS) and overall survival (OS) were calculated. RESULTS: Of 34 patients undergoing exploratory celiotomy, 24 (71%) underwent hepatic resection and 10 (29%) underwent exploration but not resection. Eighteen patients (75%) underwent complete surgical resection, while the remaining 6 underwent palliative or debulking procedures with incomplete resection. The operative resections included lobectomy (n=14), segmentectomy (4), nonanatomic resection (5), and extended lobectomy (1). The median number of resected lesions was 1, and median lesion size was 5 cm (range, 0.7-22 cm). The median disease-free interval between initial diagnosis of melanoma and development of hepatic metastases was 58 months (range, 0-264 months). Median DFS and OS estimates in the 24 patients who underwent surgical resection were 12 months (range, 0-147 months) and 28 months (range, 2-147 months), respectively. Five-year DFS and OS in this group were 12% and 29%. Macroscopically, complete resection of disease (P =.001) and histologically negative resection margins (P =.03) significantly improved DFS by univariate analysis. Patients rendered surgically free of disease also tended to have improved OS (P =.06). Median OS was 28 months for patients who underwent surgical resection compared with 4 months for patients who underwent exploration only (P<.001). CONCLUSIONS: Resection of metastatic melanoma to the liver may improve DFS and OS in selected patients, similar to resection of other metastatic sites. Therefore, patients with limited metastatic sites, including the liver, who can be rendered free of disease should be considered for complete surgical resection, as their prognosis is otherwise dismal.     

Stereotactic radiosurgery without radiation therapy providing high local tumor control of multiple brain metastases from renal cell carcinoma.

The aim of this study was to analyse treatment effects after stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT) as primary treatment for patients harboring brain metastases of renal cell carcinoma (RCC). During an 8-year period, 85 patients with 376 brain metastases from RCC underwent 134 outpatient SRS procedures. 65 % of all patients had multiple brain metastases. The median tumor volume was 1.2 cm (3) (range: 0.1 - 14.2 cm (3)). Mean prescribed tumor dose was 21.2 (+/- 3.2) Gy. Local/distant tumor recurrences were treated by additional SRS in cases of stable systemic disease. Overall median survival was 11.1 months after SRS. The local tumor control rate after SRS was 94 %. Most patients (78 %) died because of systemically progressing cancer. A KPS > 70 and RTOG class I were related to prolonged survival time. Patients of the RTOG groups I, II and III survived for 24.2 months, 9.2 months and 7.5 months, respectively. There was no permanent morbidity after SRS. 11 patients (12.9 %) showed transient radiogenic complications and 3 patients (3.5 %) died because of intratumoral bleedings after SRS. Stereotactic radiosurgery alone achieves excellent local tumor control rates for patients with small brain metastases from renal cell carcinoma.     

First-line radiosurgery of brain metastases. Interest and results of reduced dose

BACKGROUND: The minimal radiosurgical dose required to control cerebral metastases remains unknown. The aim of this study was to test whether a lower peripheral dose than usually delivered could effectively control these lesions or not. PATIENTS AND METHODS: One hundred and eighty patients presenting 356 lesions were give first-line radiosurgery between 1995 and 2001 in Pitié-Salpêtrière hospital using a 10 MV LINAC. Mean age was 59 years, sex-ratio was 1.65, mean KI was 70. The lung was the most frequent primary site (n=85), followed by melanoma (n=29), kidney (n=21), digestive tract (n=14), breast (n=11), and others (n=20). Seventy-six percent of the patients presented 1 or 2 lesions. Mean tumor Volume was 5.5 cm3. Mean peripheral dose was 14.8Gy, mean isocenter dose was 21.6Gy. RESULTS: Median survival was 7.6 months, local control rate was 90% at 6 months, 76% at 1 Year and 70% at 2 years. Median "neurological disease free" survival was 15 months. Multivariate analysis demonstrated the influence of two parameters on survival: number of lesions (p=0.001) and KI (p=0.04). The only parameter significantly correlated with disease-free survival was the number of isocenters (p=0.005). Morbidity (grade 2 RTOG) was 7.2% with no perimortality. CONCLUSIONS: Low peripheral doses delivered by radiosurgery may control brain metastases with the same efficacy and fewer side-effects as the doses usually reported in the literature.     

Efficacy and limitations of salvage gamma knife radiosurgery for brain metastases of small-cell lung cancer after whole-brain radiotherapy

Background

The efficacy and limitations of salvage gamma knife surgery (GKS) have not been thoroughly described. This study evaluated the efficacy of GKS for treating brain metastases associated with small-cell lung cancer (SCLC) after whole-brain radiotherapy (WBRT) as the first-line radiation therapy.

Methods

Forty-four patients with recurrent or new SCLC-associated brain metastases underwent GKS after receiving WBRT (median age, 62 years; median duration between WBRT and first GKS, 8.8 months). The median Karnofsky performance status (KPS) score was 100 (range, 40–100), and the median number of brain metastases at the first GKS was five. Ten patients who partially or completely responded to chemotherapy received prophylactic cranial irradiation (PCI) for limited disease.

Results

The median prescribed dose and number of lesions treated with the initial GKS were 20.0 Gy and 3.5, respectively, and the tumor control rate was 95.8 % (median follow-up period, 4.0 months). The 6-month new lesion-free survival, functional preservation rates, and overall survival were 50.0 %, 94.7 %, and 5.8 months, respectively. Neurological death occurred in 17.9 % of cases. The poor prognostic factors for new lesion-free survival time and functional preservation were >5 brain metastases and carcinomatous meningitis, respectively. Poor prognostic factors for survival time were KPS <70, >10 brain metastases, diameter of the largest tumor >20 mm, and carcinomatous meningitis. Median overall survival time from brain metastasis diagnosis was 16.9 months.

Conclusions

GKS may be an effective option for controlling SCLC-associated brain metastases after WBRT and for preventing neurological death in patients without carcinomatous meningitis.