The diagnosis and management of brain metastases.

The median survival after whole-brain irradiation of patients with brain metastases is 4 months. Because half the patients with brain metastases die of systemic cancer, for most the benefit of intensive local treatment (surgery or stereotactic radiosurgery) of brain metastases will be minimal. In particular, patients with controlled systemic disease and one to three brain metastases are candidates for intensive local treatments. Combined local treatment with whole-brain irradiation therapy improves the local control of brain metastases in comparison with whole-brain irradiation only. After the local treatment of brain metastases by either surgery or radiosurgery, overall survival is not adversely affected if whole-brain irradiation is only administered as salvage treatment at the time of relapse. New randomized trials are needed, however, to investigate this further. The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumour and non-cerebral metastases.     

脑转移瘤治疗方法的选择及疗效分析

目的探讨脑转移瘤的治疗方法并分析疗效。方法对103例脑转移瘤的肿瘤来源、大小、数目及不同治疗方法进行比较分析。结果46例（44．7％）存活1年以上。单发肿瘤行手术切除或立体定向放射外科治疗,2cm以下的多发肿瘤行放疗加化疗或行立体定向放射外科治疗其生存期较长。结论对于4cm以上大型转移瘤可行手术切除,小于4cm的单发或3cm以下的多发肿瘤应首选立体定向放射外科治疗。     

Stereotactic radiosurgery with and without whole-brain radiotherapy for newly diagnosed brain metastases

Brain metastases develop in 20-40% of cancer patients and can cause significant morbidity. In selected patients with one to three lesions, stereotactic radiosurgery may be used to improve local control. However, it is unclear whether whole-brain radiotherapy is necessary for all patients who are candidates for stereotactic radiosurgery. While whole-brain radiotherapy may improve the locoregional control of brain metastases, it may cause long-term side effects and may not improve overall survival in some patients. Its benefits should be evaluated in the context of risks of neurocognitive deterioration, either from whole-brain radiotherapy or from uncontrolled brain metastases, and the possible need for salvage treatments with the omission of initial whole-brain radiotherapy. For certain radioresistant brain metastases, the benefit of whole-brain radiotherapy to patients who have stereotactic radiosurgery is uncertain.     

立体定向置入^125I粒子治疗肺癌脑转移瘤疗效观察

目的探讨^125I粒子置入治疗肺癌脑转移瘤的临床意义和可行性。方法对63例肺癌脑转移瘤患者分为两组,其中^125I粒子置入组45例,传统手术组18例。观察两组患者术后肿瘤局部控制情况及生存时间。结果立体定向置入^125I粒子组和传统手术组比较,前者并发症少,新发颅内转移灶时间延长,生存时间增加,生存率明显提高,后者易出现肿瘤复发。结论立体定向置入^125I粒子治疗肺癌脑转移瘤可延长患者生存时间,提高患者生存质量。     

三维立体定向放疗联合全脑放疗对脑转移瘤的作用

目的探讨三维立体定向放射治疗联合全脑放疗对脑转移瘤患者神经认知功能及生存质量的影响。方法选取河南科技大学附属三门峡市中心医院肿瘤医院2012-02—2016-01收治的54例脑转移瘤患者,依据治疗方案不同分为单一组与联合组各27例。单一组实施单纯全脑放疗,于此基础上,联合组实施三维立体定向放射治疗。统计2组临床效果、不良反应情况,并对比2组治疗前后生存质量及神经认知功能变化情况。结果 2组临床总有效率相比,联合组81.49%(22/27)显著高于单一组55.56%(15/27),差异有统计学意义(P0.05);2组治疗前神经认知功能评分比较差异均无统计学意义(P0.05);与单一组相比,治疗后联合组神经认知功能评分较高,差异有统计学意义(P0.05);2组治疗前各领域生存质量评分比较差异均无统计学意义(P0.05);与单一组相比,治疗后联合组各领域生存质量评分均较高,差异有统计学意义(P0.05);联合组不良反应发生率18.52%(5/27)与单一组11.10%(3/27)相比,差异无统计学意义(P0.05)。结论脑转移瘤患者予以全脑放疗联合三维立体定向放射治疗,肿瘤控制效果更为显著,且可改善患者神经认知功能,提高生活质量,安全性较高。     

旋转式头部伽玛刀治疗脑转移瘤171例临床分析

目的 探讨旋转式头部伽玛刀在脑转移瘤治疗中的作用及疗效.方法 2010年9月至2011年10月间,我院共有171例脑转移患者接受了放射治疗,其中49人接受单纯全脑放疗（WBRT组）,占28.7％;102例接受了伽玛刀治疗,其中单独伽玛刀治疗（SRS组）50例,占29.2％;伽玛刀联合全脑放疗（WBRT＋ SRS组）72例,占42.1％.WBRT组患者接受全脑放疗40 Gy/20f/4w; SRS组患者接受旋转式头部伽玛刀治疗16 ～ 24 Gy/1f;WBRT＋ SRS组患者接受全脑放疗30 Gy/15f/3 w,后加旋转式头部伽玛刀治疗12 ～16 Gy/1f.观察3组患者的临床效果和并发症,并进行统计处理,分析三组患者的1年局部控制率和1年生存率.结果 3组患者均取得良好效果,未出现严重毒副作用;1年局部控制率分别为52.8％、81.7％、88.1％;1年生存率分别为47.6％、87.8％、92.9％.SRS组、WBRT＋ SRS组1年局部控制率和1年生存率明显高于WBRT组（P＜0.005）,差异有统计学意义;而SRS组和WBRT＋ SRS组1年局部控制率及1年生存率差异无统计学意义（P＞0.10）.结论 单纯头部伽玛刀治疗以及头部伽玛刀联合全脑放疗治疗脑转移瘤,安全有效,较传统的外照射全脑放疗,可以提高患者的生存时间及生存质量.     

Radiotherapy of cerebral metastases. 196 cases treated from 1973 to 1981

One hundred and ninety six patients underwent brain irradiation for metastases between 1973 and 1981. Complete follow-up was possible in 180 cases. CT appeared to be the best diagnostic tool. Whatever the type of the tumor, irradiation improved symptoms and signs in 65.3 p. 100 of cases and neurological status in 37 p. 100 of cases. The median survival was 4.2 months, the mean survival 6.6 months, the percent survival at 1 year 11 p. 100. It is necessary to irradiate the whole brain with doses of 40-45 Gy in 4.5 weeks. Shorter periods of irradiation allows a short inhospital stay but implies anti-oedematous treatment. Chemotherapy did not improve the results. Excision surgery had limited indications: isolated metastases, accessible site in zones with no functional importance, good performance status, local control obtained for primary tumor, no extra-cerebral metastases. Surgery must be followed by whole brain irradiation. Derivation is necessary when increased intracranial pressure and treatment resistance are present. Irradiation indications are large. The results were palliative but valuable: irradiation was always indicated except when disorders of consciousness were present. Tolerance was usually good.     

Stereotactic radiotherapy for cerebral metastases using CyberKnife

During recent decade development of frameless techniques of fixation enabled introduction of stereotactic radiation therapy in metastatic brain lesions and made possible irradiation of large foci involving or proximal to eloquent and critical brain areas. This paper focuses on comparative analysis of effectiveness of hypofractionation (HRST) and radiosurgery (SRS) using CyberKnife system in cerebral metastases. Since November 2009 till June 2011 54 patients with cerebral metastases were treated using CyberKnife system. Age of patients ranged between 25 and 77 years (mean 54 years). 16 patients received radiosurgical treatment (mean total dose was 22.5-35 Gy, number of fractions varied from 2 to 7, mean volume of irradiation was 22.69 cm3) and 8 patients were treated by HRST with RS of selected foci (mean total dose reached 23 and 30 Gy, mean volume of irradiation was 1.02 cm3 and 11.19 cm3, respectively). Indices of overall regression and stabilization of disease for HRST and SRS groups were 81% and 79%, respectively. With mean follow-up period of 12.3 (1-16.1) months median survival for SRS and HRST reached 6.38 (1-15.8) and 6.2 (0.2-16.1) months and median recurrence-free survival was 3.6 (1-13.6) and 5.5 (2-14.2) months, respectively. Obtained results confirmed biological advantages of fractionated stereotactic radiotherapy of large cerebral tumors in comparison with radiosurgery. Prospective studies with rigid criteria of inclusion are required to determine optimal dose/volume/fractionation interrelations in stereotactic radiation treatment of cerebral metastases.     

Influence of postoperative radiation therapy of cerebral metastases on survival time and disease related to living condition

Cerebral metastases are frequently observed in patients with systemic carcinoma as indication for new progress of the disease. Neurological deficits or seizures indicating cerebral metastases reduce the disease-related living conditions of the patients. Improving quality of life and survival time is the overriding goal of an early treatment after the diagnosis of cerebral metastases. Contemporary treatment include surgical removal of the cerebral metastases followed by whole brain irradiation and in some cases additional systemic chemotherapy for the primary tumor. This study was conducted to test the hypothesis that whole brain radiation following surgical removal improves the quality of life and the survival time in patients with cerebral metastasis. From January 1, 1994 to December 31, 2000, a total of 139 patients (mean age 59 +/- 2.3 years, m : f = 84 : 55) with cerebral metastases were investigated. Disease-related living conditions were assessed by Karnofsky score, the median time of follow-up was 11 months. For the analysis, patients were divided into groups with and without radiation therapy. Additionally, groups of patients with singular and two brain metastases were defined. In patients with singular brain metastases neither the survival time nor disease-related living conditions during the remaining life time was increased by postoperative whole brain irradiation. Almost all patients died due to the progression of the primary tumor. Patients with more than one metastases seemed to have a slight but not significant benefit from irradiation therapy after surgical removal of all metastases. In conclusion, these results indicate that an uncritical irradiation therapy of neurocranium after surgical removal of cerebral metastases is not beneficial in terms of survival time or disease-related living conditions.     

Surgical treatment of brain metastasis: a review

Brain metastasis is the most common intracranial tumor in adults. Currently, treatment of brain metastasis requires multidisciplinary approach tailored for each individual patient. Surgery has an indispensible role in relieving intracranial mass effect, improving neurological status and survival while providing or confirming neuropathological diagnosis with low mortality and morbidity rates. Besides the resection of a single brain metastasis in patients with accessible lesions, good functional status, and absent/controlled extracranial disease; surgery is proven to play a role in management of multiple metastases. Surgical technique has an impact on the outcome since piecemeal resection rather than en bloc resection and leaving infiltrative zone behind around resection cavity may have a negative influence on local control. Best local control of brain metastasis can be accomplished with optimal surgical resection involving current armamentarium of preoperative structural and functional imaging, intraoperative neuromonitoring, and advanced microneurosurgical techniques; followed by adjunct therapies like stereotactic radiosurgery, whole brain radiotherapy, or intracavitary therapies. Here, treatment options for brain metastasis are discussed with controversies about surgery.     

Metastases to the brain: current management perspectives

Brain metastases are ten-times more common than primary brain tumors and are a common complication in patients with systemic cancer. The most common sources of brain metastases are lung and breast cancers, although in 15% of patients, the primary site is unknown. Optimal treatment is dependant upon tumor location, size, number of tumors and status of the systemic disease. Currently, management of brain metastases with surgery, radiotherapy and stereotactic radiosurgery is known to improve the quality of life and even life expectancy for selected patients. Techniques under investigation include focal radiation techniques, magnetic resonance imaging guided thermal ablation of metastases, drug delivery modes that bypass the blood-brain barrier and novel drug and molecular therapeutics. Efforts are ongoing to understand the molecular biology of brain metastases.     

Therapeutic management of brain metastasis

This review focuses on the management of brain metastases. The four main modes of therapy are discussed: whole brain radiation therapy (WBRT), surgery, radiosurgery, and chemotherapy. Young patients with limited extracranial disease may benefit from surgical resection of a single brain metastasis, and from radiosurgery (or stereotactic radiotherapy) if two to four brain metastases are present. Whether WBRT after surgery or radiosurgery is beneficial is uncertain. Therefore, two approaches can be justified in patients with a good prognosis: WBRT after surgery or radiosurgery, or alternatively, observation with MRI follow-up after surgery or radiosurgery. A hyperfractionated radiation scheme is then to be preferred to limit late toxicity of WBRT. Patients with extensive extracranial tumour activity or impaired quality of life may benefit from radiosurgery (one to four brain metastases), or from shorter WBRT schedules. We propose a decision tree on the various ways to treat brain metastasis.     

Management of brain metastases

Brain metastases represent a common and devastating complication of cancer. With advances in surgery, radiology, and medical and radiation oncology, the number of treatment options have greatly increased. In addition, the prognosis for patients can vary widely depending on factors such as the number of lesions, extent of extracranial disease, age, and functional status. Recently, the possible impairment of whole brain radiation therapy on neurocognitive function has been a subject of concern and debate. Thus, the use of whole brain radiation therapy in conjunction with other treatment modalities should be optimized to ensure the best outcomes with regard to tumor control and functional status. As a result, patient management has become controversial, with strong opinions often dictating “optimal” therapy. This review of the management of brain metastases focuses on whole brain radiation therapy, surgery, stereotactic radiosurgery, radiation sensitizers, and clinical trials.     

Conventional external radiotherapy in the management of clivus chordomas with overt residual disease

Cranial chordomas are uncommon tumors accounting for less than 1% of all intracranial neoplasms. Although they are slowly growing, rarely metastasising tumors, cranial chordomas are challenging to treat due to their critical location, invasive nature and aggressive recurrence. The aim of this retrospective study was to evaluate the role of conventional irradiation in the treatment of clival chordomas with overt residual disease after incomplete surgery. Between January 1979 and December 1997, 18 patients with histologically confirmed clival chordoma were treated with radiotherapy. Median age at the time of diagnosis was 32 years. The mean duration of the symptoms before diagnosis was 33.9 months. Median tumor diameter at initial presentation was 5 cm (range, 3–7 cm). The type of surgical procedure was subtotal excision in 11 patients and biopsy in 7. Radiation treatment was delivered with megavoltage units, and total doses between 50 Gy and 64 Gy (median, 60 Gy) were administered with conventional daily fractions. One patient received additional 12.50 Gy with linear accelerator-based stereotactic radiosurgery after subtotal excision and external irradiation. The mean follow-up time was 43.2 months. Overall survival at 5 years was 35%. Eleven patients showed progression after radiotherapy. The median time to progression after radiotherapy was 40.8 months (38.4–43.2) with a 5-year progression-free survival of 23%. Five patients (29.4%) showed symptomatic relief after radiotherapy while persistent symptoms were recorded for 6 patients. Incomplete surgery and conventional external radiotherapy with a dose of around 60 Gy seem to be inadequate in the treatment of clival chordomas. Received: 31 March 2000 / Accepted in revised form: 11 July 2000     

Current strategies in the surgical management of cerebral metastases: an evidence-based review

Metastatic tumours are the most common form of cerebral neoplasm, occurring in up to 40% of patients with systemic cancer. Although the presence of metastatic disease portends limited survival, aggressive management of cerebral metastases is vital to preventing death from neurological causes and prolonging functional independence. Due to advancement in neurosurgical techniques and the advent of stereotactic radiosurgery as a non-operative alternative, current decision making for selecting the appropriate local treatment often results in clinical equipoise. In addition, the traditional blanket application of whole brain radiation has come under scrutiny as new evidence regarding the deleterious neurocognitive effects of ionizing radiation emerges. The completion of a series of randomized studies comparing the efficacy of surgery, radiosurgery, whole brain radiotherapy and various combined approaches for cerebral metastases in recent years has shed important light on addressing some of these issues. The focus of this review is to summarize the key findings and outline a practical approach for the management of cerebral metastases.     

Brain metastases

Despite advances in the treatment of cancer, brain metastases appear to be increasing in frequency and are associated with a poor prognosis. Type of tumor, age, performance status, and extent of systemic disease are important prognostic factors that should be taken into consideration when making treatment decisions. Patients with a good performance status and controlled systemic disease may benefit from aggressive focal therapies (surgery or radiosurgery). Whole brain radiotherapy seems to increase local control but is associated with the risk of delayed cognitive deterioration in long-term survivors. In spite of this, whole brain radiotherapy remains the standard of care for those patients with poorer prognosis and for the treatment of recurrence after focal therapy. Chemotherapy has a limited role in the treatment of brain metastases but should be considered in selected patient populations.     

Management of brain metastases

Brain metastases occur in 20–40 % of patients with cancer and their frequency has increased over time. Lung, breast and skin (melanoma) are the commonest sources of brain metastases, and in up to 15 % of patients the primary site remains unknown. After the introduction of MRI, multiple lesions have outnumbered single lesions. Contrast-enhanced MRI is the gold standard for the diagnosis. There are no pathognomonic features on CT or MRI that distinguish brain metastases from primary malignant brain tumors or nonneoplastic conditions: therefore a tissue diagnosis by biopsy should be always obtained in patients with unknown primary tumor before undergoing radiotherapy and/or chemotherapy. Some factors are prognostically important: a high Performance Status, a solitary brain metastasis, an absence of systemic metastases, a controlled primary tumor and a younger age. Based on these factors, subgroups of patients with different prognosis have been identified (RPA class I, II, III). Symptomatic therapy includes corticosteroids to reduce vasogenic cerebral edema and anticonvulsants to control seizures. In patients with newly diagnosed brain metastases prophylactic anticonvulsants should not be used routinely. The combination of surgery and whole-brain radiotherapy (WBRT) is superior to WBRT alone for the treatment of single brain metastasis in patients with limited or absent systemic disease and good neurological condition. Complete surgical resection allows a relief of intracranial hypertension, seizures and focal neurological deficits. Radiosurgery, alone or in conjunction with WBRT, yields results which are comparable to those reported after surgery followed by WBRT, provided that lesion's diameter does not exceed 3–3.5 cm. Radiosurgery offers the potential of treating patients with surgically inaccessible metastases. Still controversial is the need for WBRT after surgery or radiosurgery: local control seems better with the combined approach, but overall survival does not improve. Late neurotoxicity in long surviving patients after WBRT is not negligeable; to avoid this complication patients with favorable prognostic factors must be treated with conventional schedules of RT, and monitoring of cognitive functions is important. WBRT alone is the treatment of choice in patients with single brain metastasis not amenable to surgery or radiosurgery, and with an active systemic disease, and in patients with multiple brain metastases. A small subgroup of these latter may benefit from surgery. The response rate of brain metastases to chemotherapy is similar to the response rate of the primary tumor and extracranial metastases, some tumor types being more chemosensitive (small cell lung carcinoma, breast carcinoma, germ cell tumors). New radiosensitizers and cytotoxic or cytostatic agents, and innovative technique of drug delivery are being investigated. Received: 20 May 2002, Accepted: 23 May 2002 Correspondence to Riccardo Soffietti, MD     

Successful long-term treatment of multiple metastases from renal cell carcinoma: combination of stereotactically guided percutaneous single-dose convergent beam irradiation and surgery

The case of a patient suffering from renal cell carcinoma and recurrent brain metastases shows how the survival period can be significantly prolonged by a combination of stereotactically guided percutaneous single-dose convergent beam irradiation and surgery. This 58-year-old man's left kidney was completely excised because of a renal cell carcinoma. After 18 months and 25 months, respectively, a right frontal brain metastasis was operated on. In the next 7 years, biannual MRI checks were carried out which successively showed five different brain metastases, each of which was immediately subjected to single-dose stereotactic irradiation (median dosage: 20 Gy prescribed to the 80% isodose). In the following 2 years, operations were carried out on two metastases which could not be treated by radiation because of their considerable size and partial compression of the ventricle. In the next 3 years, four more brain metastases were subjected to single-dose stereotactic irradiation. There were no metastases in the other organs. At present, the patient is in good clinical condition and mobile. A negative prognosis is usually delivered for patients suffering from renal cell carcinoma and brain metastasis. However, in individual cases, the survival period can be significantly prolonged by regular MRI examinations and a combination of neurosurgery and single-dose stereotactic irradiation.     

Current management of metastatic brain disease

Brain metastases are the most common intracranial tumor in adults. The incidence of metastases is thought to be rising due to better detection and treatment of systemic malignancy. More widespread use and improved quality of MRI may lead to early detection of brain metastases. Available evidence suggests that survival is longer and quality of life improved if brain metastases are treated aggressively. This article reviews current therapeutic management used for brain metastases. To select the appropriate therapy, the physician must consider the extent of the systemic disease, primary histology, and patient age and performance status, as well as the number, size, and location of the brain metastases. Available treatment options include whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), surgery, and chemotherapy. Multidisciplinary approaches such as the combination of WBRT with SRS or surgery have shown superior results in terms of survival time, neurocognitive function, and quality of life. The utility and optimal use of chemotherapy and radiosensitizing agents is less clear. It is hoped that further advances and multidisciplinary approaches currently under study will result in improved patient outcomes.