A comparison of survival rates for treatment of melanoma metastatic to the brain

Introduction: A retrospective review of 91 patients with brain metastases from malignant melanoma treated at New York University Medical Center between 1989-1999. Overall survival was the outcome evaluated. Methods: Charts of 91 patients having malignant melanoma with brain metastases were reviewed. Cases were stratified according to therapy: surgical excision, surgical excision plus whole brain radiation therapy, gamma knife stereotactic radiosurgery, gamma knife stereotactic radiosurgery plus whole brain radiation therapy, and whole brain radiation therapy alone. Patients treated with gamma knife stereotactic radiosurgery plus radiation therapy were combined with patients treated with surgical excision plus radiation therapy and compared to those treated with radiation therapy alone. Prognostic characteristics of the two groups were compared and survival curves were generated using the Kaplan-Meier method. The Cox proportional hazards model was used to control for prognostic factors that differed between the groups. Results: Patients treated with gamma knife stereotactic radiosurgery or surgical excision plus radiation therapy were younger, less likely to present with symptoms, and presented with fewer metastases to the brain than patients treated with radiation therapy alone. A survival benefit of 7.3 months (p = 0.05) was found to be associated with gamma knife radiosurgery or surgical excision plus radiation therapy over radiation therapy alone after controlling for differences in age, number of brain lesions, and presence of symptoms. Discussion: This retrospective study of 91 patients treated for melanoma metastases to the brain attempts to examine the effectiveness of different treatments in prolonging survival. Our results suggest that surgical excision or stereotactic radiosurgery with gamma knife in addition to radiation therapy may be more effective than radiation alone at prolonging survival for patients with a limited number of brain lesions. Conclusion: Survival of patients with melanoma metastases to the brain may be prolonged by treatment with gamma knife stereotactic radiosurgery or surgical excision plus whole brain radiation therapy.     

Stereotactic radiosurgery of the brain using a standard linear accelerator: a study of early and late effects

Between February 1986 and December 1988, 44 patients were treated with stereotactic radiosurgery using a standard linear accelerator. Twenty one patients were treated for cerebrovascular abnormalities and 23 patients were treated for intracranial tumors. Fifteen of the 23 patients treated for intracranial tumors had received previous radiotherapy. The range of doses given by radiosurgery was 1000-2500 cGy. Nausea and vomiting occurred in seven patients within six hours of treatment. The incidence and symptoms were correlated with the dose of radiation to the vomiting center (area postrema) with the median dose to the postrema in symptomatic patients being 618 cGy compared to a range of less than 5 to 184 cGy in the remaining 36 asymptomatic patients. Temporary alopecia occurred in a single patient who received 400 cGy to the scalp. Alopecia did not occur in the remaining 43 patients who received from less than 5 to 175 cGy. Two patients treated for arteriovenous malformations developed an enhancing lesion on CT scanning (one with cerebral edema) on follow-up CT scanning six and twenty-eight months following radiosurgery. The location of these enhancing lesions corresponded to the volumes treated. In one patient, the enhancing pattern and edema disappeared within 18 months of treatment and no neurological deficits developed. Aphasia occurred in one patient treated for a recurrent glioma two hours following treatment to the left temporal lobe and cleared within 12 h of radiosurgery. One patient with an arteriovenous malformation of the pons developed weakness of the contralateral arm and leg six weeks following treatment and this has slowly resolved over the last 12 months. In conclusion, the complications to date have been self-limited and appear to be directly related to the dose and area of brain treated. Prior radiation therapy has not been associated with increased risk of complication in patients treated with radiosurgery for recurrent tumors to date.     

Brain metastases

Opinion statement Brain metastases are an increasingly common complication in patients with systemic cancer. The optimal treatment for each patient depends on careful evaluation of several factors: the location, size, and number of brain metastases; the patient's age, general condition, and neurologic status; and the extent of systemic cancer to name a few. For patients with a single brain metastasis and limited systemic disease, the standard treatment is surgical resection followed by whole brain radiation therapy. In patients with a small, single metastasis, stereotactic radiosurgery is probably comparable to surgery. Patients with several metastases (up to three) and controlled systemic disease can be treated with whole-brain radiation and stereotactic radiosurgery. Patients with multiple metastases (more than three) are generally treated with whole-brain radiation alone. Radiosurgery is effective in treating patients with a limited number of recurrent brain metastases and stable systemic diseases. Surgery may have a role in patients with a large symptomatic recurrent lesion producing mass effect. Reirradiation and chemotherapy may have a limited role in patients with multiple recurrent metastases.     

Stereotactic radiosurgery for metastatic brain tumors

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

Multimodality treatment of melanoma brain metastases incorporating stereotactic radiosurgery (SRS)

BACKGROUND: Brain metastases are a frequent complication in advanced melanoma. A 3.6 to 4.1-month median survival has been reported after treatment with whole brain radiotherapy. We performed a retrospective analysis of our institutional experience of multimodality treatment utilizing linear accelerator (Linac)-based stereotactic radiosurgery (SRS). METHODS: Forty-four melanoma patients with brain metastases underwent 66 SRS treatments for 156 metastatic foci between 1999 and 2004. Patients were treated with initial SRS if or=70, but 37 patients had active systemic metastases (Recursive Partition Analysis Class 2). Survival was calculated from the time of diagnosis of brain metastases. Minimum follow-up was 1 year after SRS. The potential role of prognostic factors on survival was evaluated including age, sex, interval from initial diagnosis to brain metastases, surgical resection, addition of whole brain radiotherapy (WBRT), number of initial metastases treated, and number of SRS treatments using Cox univariate analysis. RESULTS: The median survival of melanoma patients with brain metastases was 11.1 months (95% confidence interval [CI]: 8.2-14.9 months) from diagnosis. One-year and 2-year survivals were 47.7% and 17.7%, respectively. There was no apparent effect of age or sex. Surgery or multiple stereotactic radiotherapy treatments were associated with prolonged survival. Addition of WBRT to maintain control of brain metastases in a subset of patients did not improve survival. CONCLUSIONS: Our results suggest that aggressive treatment of patients with up to 5 melanoma brain metastases including SRS appears to prolong survival. Subsequent chemotherapy or immunotherapy after SRS may have contributed to the observed outcome.     

The role of radiosurgery in the management of malignant brain tumors

Opinion statement Stereotactic radiosurgery (SRS) provides the means for creating lesions in deep-seated areas of the brain inaccessible to invasive surgery, using single high doses of focused ionizing radiation, administered using stereotactic guidance. It is a surgical technique designed to produce a specific radiobiological effect within a sharply defined target region in a single treatment session. Its technical application requires a stereotactic coordinate system, highly accurate patient repositioning (usually fixed), and multiple convergent beams of photon radiation. SRS appears to provide no benefit in the upfront treatment of newly diagnosed malignant gliomas but may be used to effectively palliate small well-demarcated volumes of recurrent disease. For selected patients with brain metastases treated with whole-brain radiation therapy (WBRT), the addition of SRS improves median survival. In selected patients with brain metastases, it is also rational to withhold WBRT in favor of radiosurgery alone, with WBRT reserved for salvage without a decrease in median survival time.     

Survival and prognostic factors in patients with brain metastases from malignant melanoma

AIM: We wanted to determine the factors influencing survival in a retrospective review of patients with melanoma brain metastases to permit more specific recommendations regarding therapy. PATIENTS AND METHODS: We reviewed the data of 100 patients treated at the Department of Dermatology and Radiation Oncology, University of Zurich, and the Klinik im Park, Zurich. Information on potential prognostic factors (age, sex, location of the primary tumor, Clark level, Breslow index, histological type, number of brain metastases, stage at initial diagnosis, location of brain metastases, and therapy) was collected from the medical records of 100 patients treated between 1966 and 2002. Univariate and multivariate analyses were performed to identify significant prognostic factors. RESULTS: The overall median survival time was 4.8 months, with 6-month, 1-year and 2-year survival percentages of 36, 14 and 5%, respectively. Univariate analysis indicated that survival correlated significantly with radiotherapy (partial and whole brain), surgery, stereotactic radiosurgery, chemotherapy, Clark level and Breslow index. Treatment with temozolomide (p = 0.052) and number of brain metastases (p = 0.07) failed to be statistically significant. Multivariate analysis confirmed radiotherapy (partial and whole brain), surgery, stereotactic radiosurgery, chemotherapy and the location of brain metastases as independent and significant prognostic factors of survival. The remaining factors did not reach statistical significance in multivariate analysis. CONCLUSION: Radiotherapy, chemotherapy and especially surgery and stereotactic radiosurgery seem to significantly prolong survival, as shown by multivariate analysis. Treatment with temozolomide will possibly play an important role in the future management of patients with brain metastases from cutaneous melanoma, but further prospective studies to verify this assumption are urgently needed.     

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.     

Pulsed Reduced Dose-rate Radiotherapy as Re-irradiation for Brain Metastasis in a Patient with Lung Squamous-celled Carcinoma

The recurrence and progression of brain metastases after brain irradiation are a major cause of mortality and morbidity in patients with cancer. The risk of radiation-induced neurotoxicity and efficacy probably leads oncologists to not consider re-irradiation. We report the case of a 48-year-old Asian male diagnosed with squamous cell lung cancer and multiple brain metastases initially treated with 40 Gy whole-brain radiotherapy and 20 Gy partial brain boost. Fourteen gray stereotactic radiosurgery as salvage for brain metastases in the left occipital lobe was performed after initial irradiation. The recurrence of brain metastases in the left occipital lobe was demonstrated on magnetic resonance imaging at 9 months after initial radiotherapy. He received the second course of 28 Gy stereotactic radiosurgery for the recurrent brain metastases in the left occipital lobe. The third relapse of brain metastases was demonstrated by a magnetic resonance imaging scan at 7 months after the second radiotherapy. The third course of irradiation was performed because he refused to undergo surgical resection of the recurrent brain metastases. The third course of irradiation used a pulsed reduced dose-rate radiotherapy technique. It was delivered in a series of 0.2 Gy pulses separated by 3-min intervals. The recurrent brain metastases were treated with a dose of 60 Gy using 30 daily fractions of 2 Gy. Despite the brain metastases receiving 162 Gy irradiation, this patient had no apparent acute or late neurologic toxicities and showed clinical improvement. This is the first report of the pulsed reduced dose-rate radiotherapy technique being used as the third course of radiotherapy for recurrent brain metastases.     

Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: impact on local control

PURPOSE: Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy). RESULTS: All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases. CONCLUSIONS: Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.     

Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy

BackgroundThe anti-programmed death-1 (anti-PD-1) therapy nivolumab has significant clinical activity in patients with metastatic melanoma. However, little is known about the safety and outcomes in patients receiving anti-PD-1 therapy and stereotactic radiation for the treatment of brain metastases (BMs).Patients and methodsData were analyzed retrospectively from two prospective nivolumab protocols enrolling 160 patients with advanced resected and unresectable melanoma at a single institution. Patients were included if BMs were diagnosed and treated with stereotactic radiation within 6 months of receiving nivolumab. The primary end point of this study was neurotoxicity; secondary end points included BM control and survival.ResultsTwenty-six patients with a total of 73 BMs treated over 30 sessions were identified. Radiation was administered before, during and after nivolumab in 33 lesions (45%), 5 lesions (7%), and 35 lesions (48%), respectively. All BMs were treated with stereotactic radiosurgery (SRS) in a single session except 12 BMs treated with fractionated stereotactic radiation therapy, nine of which were in the postoperative setting. One patient experienced grade 2 headaches following SRS with symptomatic relief with steroid treatment. No other treatment-related neurologic toxicities or scalp reactions were reported. Eight (11%) local BM failures with a ≥20% increase in volume were noted. Of these lesions, hemorrhage was noted in 4, and edema was noted in 7. Kaplan–Meier estimates for local BM control following radiation at 6 and 12 months were 91% and 85%, respectively. Median overall survival (OS) from the date of stereotactic radiation and nivolumab initiation was 11.8 and 12.0 months, respectively, in patients receiving nivolumab for unresected disease (median OS was not reached in patients treated in the resected setting).ConclusionsIn our series, stereotactic radiation to melanoma BMs is well tolerated in patients who received nivolumab. BM control and OS appear prolonged compared with standard current treatment. Prospective evaluation is warranted.     

Melanoma in the brain: biology and therapeutic options

The development of brain metastases is a frequent occurrence in patients with disseminated melanoma and contributes to a disproportionate degree of morbidity and mortality. The prognosis is markedly reduced once a patient is diagnosed with central nervous system disease. Definitive therapeutic interventions with resection or stereotactic radiosurgery have improved outcomes and become standard approaches in the management of melanoma brain metastases. With the inclusion of whole-brain radiation in these interventions, there has been a reduction in local recurrences, but no improvement in the overall survival. Still, many patients are not candidates for surgery nor radiotherapy nor develop progressive central nervous system disease after definitive therapy. As new immune-based and targeted therapeutic agents are developed for the treatment of metastatic melanoma, understanding their activity in brain metastases is necessary for effective patient management. In this review, we discuss the biology of brain metastases in metastatic melanoma, current treatment approaches with surgery and radiotherapy, and future systemic therapeutic strategies.     

X射线立体定向放射治疗多发脑转移瘤的价值

目的　探讨X射线立体定向放射治疗多发脑转移瘤的疗效。方法　在 4种预后因素(年龄、治疗前卡氏评分、有无其他部位转移及转移灶数目 )相同或相似的条件下 ,配对选择两组病例。X射线立体定向放射治疗加常规放射治疗组 (研究组 )和常规放射治疗组 (对照组 )各 53例。在研究组中 ,X射线立体定向放射治疗采用单次照射 40例 ,分次照射 1 3例 ;单次靶区平均周边剂量为 2 0Gy,分次照射剂量为 4～ 1 2Gy/次 ,2次 /周 ,总剂量为 1 5～ 30Gy。X射线立体定向放射治疗结束后即开始全脑放射治疗。对照组采用全脑照射 30～ 40Gy,3～ 4周。结果　研究组和对照组中位生存期分别为1 1 .6、6 .7个月 (P <0 .0 5) ;1年生存率分别为 44 .3 %、1 7.1 % (P <0 .0 1 ) ;1年局部控制率分别为50 .9%、1 3 .2 % (P <0 .0 5) ;治疗后 1个月卡氏评分增加者分别占 69.8%、30 .2 % (P <0 .0 1 ) ;治疗后 3个月影像学上的有效率分别为 82 .0 %、55 .0 % (P <0 .0 1 )。在死因分析中 ,研究组死于脑转移的占2 3 .3 % ,比对照组的 51 .0 %低 (P <0 .0 5)。两组病例放射并发症的发生率相似。结论　对于多发脑转移瘤 ,X射线立体定向放射治疗加常规放射疗在提高局部控制率、延长生存期和提高生存质量方面均优于单纯放射治疗。     

Fractionated Radiosurgery for Brain Metastases in 43 Patients with Breast Carcinoma

About 15% of metastatic breast carcinoma patients are diagnosed with brain metastases. Historically, the majority are treated with palliative external whole-brain radiation with a median survival of 4 months. We examined stereotactic radiosurgery's effect on treatment outcome in such patients. Four hundred and fifty four consecutive patients with brain metastases were treated with stereotactic radiosurgery at Staten Island University Hospital, NY, between 1991 and 1999. The medical records of 60 women with histologically confirmed breast cancer were retrospectively reviewed. Forty-three patients (71%) received fractionated radiosurgery (4×600cGy) and form the core of this report. Sixty five percentage had been previously unsuccessfully treated by whole-brain radiation or had recurrence after craniotomy. Survival was calculated by the Kaplan–Meier method. The median age at diagnosis of brain metastases was 52 years, with median interval of 49 months following the diagnosis of tumor primary. Median survival from brain diagnosis reached 13.6 months. Overall median survival from radiosurgery treatment was 7.5 months. Fifteen patients with one or two brain lesions survived a median of 11.5 months. For the fractionated cohort of patients 1- and 2-year actuarial survival was 28.2% and 12.8%, respectively. Three patients are alive at 32, 34 and 64 months, respectively. We conclude that fractionated radiosurgery improves survival of patients with brain metastases from breast cancer, especially those with small lesions, good functional status and no other metastatic disease. These patients should be encouraged to consider radiosurgery, possibly before WBRT. Considering our 7.5 months overall survival including patients with multiple metastases, and patients with progressive brain metastases despite extensive standard therapy and often systemic disease, these results suggest that radiosurgery could benefit breast cancer patients with brain metastases and extend life.     

Stereotaxic radiosurgery for brain metastases: the importance of adjuvant whole brain irradiation.

Stereotaxic radiosurgery delivered from a modified 4 MV linear accelerator was used to treat 47 brain metastases in 27 patients at Stanford. Response was assessed in 41 lesions. Histopathologies included adenocarcinoma (24 lesions), renal cell carcinoma (9 lesions), melanoma (6 lesions), and squamous cell carcinoma (2 lesions). Follow-up ranged from 1.0-16.5 months, with a median of 5.0 months. Radiographic local control was achieved in 88% of the lesions. Three patients developed enlarging contrast-enhancing lesions in the radiosurgical field; one of these was biopsied and revealed necrosis with no viable tumor. Adjuvant whole brain irradiation (10 patients) was associated with regional intracranial control in 80% of patients. This was statistically superior (p = 0.0007) to the regional intracranial control rate achieved when radiosurgery alone was employed (6 patients). Most patients reported resolution of their neurologic symptoms, and were able to discontinue dexamethasone without impairment of neurologic function.     

Stereotactically delivered cranial radiation therapy: a ten-year experience of linac-based radiosurgery in the UK

In 1989, linear accelerator (linac)-based cranial stereotactic radiation therapy ('radiosurgery') was introduced in the UK at St Bartholomew's Hospital; a new, relocatable stereotactic frame was first used at the same time, allowing fractionated stereotactic radiotherapy. In the first decade of clinical practice using this technology, some 200 patients with blood vessel tumours/malformations have been treated, together with another 200 suffering from other conditions. The usefulness of this technique for cerebral arteriovenous malformations (AVM) has been demonstrated, and also a significant cure rate for AVM of >3 cm diameter (which is larger than for those previously reported after treatment on the gamma unit), albeit attended by a higher complication rate. The epilepsy associated with AVM is much improved by successful radiotherapy. The usefulness of radiosurgery for glomus tumours has been confirmed and new data published on the efficacy of the technique for haemangioblastoma, with new radiation therapy strategies designed for patients with von Hippel-Lindau disease. The acoustic neuroma treatment results have included improvements in hearing (a result not reported in the gamma unit literature), which are ascribed to the lower internal dose gradient within the target volume. Fractionation will, it is argued, also lead to sparing of the special sensory cochlear nerve. The risks of radiosurgery to the brainstem for chordoma of the mid-clivus are reduced by using a 'spacer' technique for the prepontine space. For meningiomas involving the cavernous sinus, conventionally fractionated radiotherapy is recommended when the meningeal base diameter exceeds 3.0 cm and radiosurgery (utilizing fractionation where appropriate) is advised for smaller lesions. Thus far, radiosurgery indications for pituitary adenomas have been restricted to recurrences after conventional radiotherapy, usually those in the cavernous sinus. In therapy for recurrent craniopharyngioma, it is argued that fractionation delivered via the relocatable frame will be important, particularly when the disease envelops the optic chiasma. For semicystic/semisolid craniopharyngiomas, the stereotactic delivery of colloidal yttrium-90 into a cystic element is useful, while stereotactic radiosurgery is delivered to the solid component. Staff at this centre consider that radiosurgery for low-grade gliomas, perhaps as boost therapy after conventional fractionation, is worthy of more research. We have been extremely selective in the use of radiosurgery for brain metastases (2% of patients, compared with about 30% in some Gamma Knife units), but future indications may become broader, probably using it as a booster technique after whole-brain conventionally-fractionated radiotherapy. Positron emission tomography scanning, co-registered with magnetic resonance imaging, allows the 'boost' concept in radiosurgery to become a sophisticated and accurate reality. Post-radiosurgical sequelae have been placed within a standard framework classification. New observations are being made with regard to subacute reactions: late-responding intrinsic and extra-axial tumours may swell in the subacute period, prior to shrinkage, and be attended by symptomatic surrounding brain oedema.     

Vemurafenib and radiation therapy in melanoma brain metastases

Brain metastases in malignant melanoma carries a poor prognosis with minimal response to any therapy. The purpose of this pilot analysis was to find the effectiveness of vemurafenib, an oral BRAF inhibitor, and radiation therapy in V600 mutated melanoma with brain metastases. BRAF mutation status of the melanoma patients was determined by real-time PCR assay. Retrospective analysis was performed on twelve patients who had the mutation and were treated with either stereotactic radiosurgery or whole brain radiation therapy prior to or along with vemurafenib at a dose of 960 mg orally twice a day. Clinical and radiological responses, development of new brain metastases, overall survival and toxicity were assessed. Improvement in neurological symptoms was seen in 7/11 (64 %) following therapy. Radiographic responses were noted in 36/48 (75 %) of index lesions with 23 (48 %) complete responses and 13 (27 %) partial responses. Six month local control, freedom from new brain metastases and overall survival were 75, 57 and 92 %. Four patients had intra-tumoral bleed prior to therapy and two patients developed steroid dependence. One patient experienced radiation necrosis. This retrospective study suggests that melanoma patients with brain metastases harboring BRAF mutation appear to be a distinct sub-group with a favorable response to vemurafenib and radiation therapy and acceptable morbidity.     

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.     

Focal 3D conformal high-dose hypofractionated radiotherapy for brain metastases

The optimal management of patients with few brain metastases is complex. On one hand, stereotactic radiation therapy is a keystone of treatment but is only applicable to highly selected patients fulfilling specific criteria who have access to an adequate radiation unit. On the other, whole-brain radiation therapy may improve survival, but deleterious effects on neurocognitive functions are well known. It has, however, been reported that selected subgroups of patients may benefit from focal dose escalation to brain metastases to prolong survival and the time to intracranial disease progression. Here, we discuss a clinical case to consider the interest of a focal high-dose hypofractionated radiation delivered through a conventional linear accelerator on a large brain metastasis for a patient with metastatic melanoma excluded for stereotactic radiotherapy.     

Radiation therapy in the management of brain metastases from renal cell carcinoma

Brain metastases from renal cell carcinoma (RCC) cause significant morbidity and mortality. More effective treatment approaches are needed. Traditionally, whole-brain radiotherapy has been used for palliation. With advances in radiation oncology, stereotactic radiosurgery and hypofractionated stereotactic radiotherapy have been utilized for RCC brain metastases, producing excellent outcomes. This review details the role of radiotherapy in various subgroups of patients with RCC brain metastases as well as the associated toxicities and outcomes. Newer radiosensitizers (eg, motexafin gadolinium [Xcytrin]) and chemotherapeutic agents (eg, temozolomide [Temodar]) used in combination with radiotherapy will also be discussed.