Chemotherapy is reserved for patients with an unresectable recurrence refractory to radiotherapy.
Brain Metastases 脑转移
Metastases to the brain are the most common intracranial [,intr?'kreini?l]tumors in adults and occur ten times more frequently than do primary brain tumors.
Metastases to the brain are the most common intracranial颅内的 [,intr?'kreini?l]tumors in adults成人 and occur存在 ten times十倍 more frequently 频繁than do primary brain tumors.
脑转移是最常见的成人颅内肿瘤，频率（发病率）是原发脑肿瘤的十倍。
More recent population-based data reported that about 8%to 10%of cancer patients are inflicted by symptomatic metastatic tumors in the brain.
More recent较新的 population-based data reported that about 8%to 10%of cancer patients are inflictedvt. 造成；使遭受（损伤、痛苦等）；给予（打击等） by symptomatic metastatic tumors in the brain. 最近的以人群为基础的数据报道,大约8%至10%的癌症患者都存在有症状的脑转移瘤。 A much higher incidence upon autopsy尸检 has been reported. 据报道经过尸体解剖发生率要高得多。
As a result of advances in the diagnosis and treatment,most patients improve with treatment and do not die of these metastatic lesions.
因为诊断和治疗发展,大多数病人通过治疗好转,不会死于这些转移病灶。
Primary lung cancers are the most common source,accounting for half of intracranial [,intr?'kreini?l] metastases,although melanoma黑色素瘤 has been documented to have the highest predilection偏爱 to spread to the brain. 原发性肺癌是最常见的来源,占一半的颅内转移,尽管黑色素瘤被证明是最偏爱扩散到大脑。
Diagnosis of CNS involvement损伤 is becoming more common in patients with breast cancer as therapy for metastatic disease is improving.220
因为转移性疾病治疗的改进，乳腺癌患者中枢神经系统损伤的诊断日趋常见。
Almost 80%brain metastases occur in the cerebral hemispheres,an additional 15%occur in the cerebellum,and 5%occur in the brainstem.221
几乎80%的脑转移发生在大脑半球,额外的15%发生在小脑,5%发生在脑干
These lesions typically follow a pattern of hematogenous spread to the gray-white junction where the relatively narrow caliber of the blood vessels tends to trap tumor emboli.
These lesions 病变typically代表性 follow a pattern模式 of hematogenous spread血行转移 to the gray-white junction结合部 where the relatively相对 narrow caliber 管径of the blood vessels tends趋势倾向 to trap陷阱 捕获 tumor emboli肿瘤栓子.
这种病变代表性的遵循血行转移模式侵及灰白质结合处，有相对狭窄的血管管径，有成为肿瘤栓子陷阱倾向的， The majority of cases have multiple brain metastases evident on MRI scans. 大多数情况下多发脑转移在磁共振扫描明显显影。
The presenting signs and symptoms of metastatic brain lesions are similar to those of other mass lesions in the brain,such as headache,seizures,and neurological impairment.
转移性脑部病变表现的症状和体征与脑部大多数的病变相似,如头痛、癫痫发作、和神经损伤。 Treatment Overview综诉 Surgery
Advances in surgical technique have rendered upfront resection followed by WBRT the standard of care for solitary brain metastases.
手术技术的进步提出前期手术切除，然后行全脑放疗，成为单发脑转移的标准治疗
A retrospective analysis of 13,685 patients admitted for resection of metastatic brain lesions showed a decline in in-hospital mortality from 4.6%in the period 1988-1990 to 2.3%in the period 1997-2000.222
High-volume hospitals and surgeons produced superior outcomes.
Patchell and his group conducted a study that randomized 95 patients with single intracranial metastases to complete resection alone or surgery plus adjuvant WBRT.223
Postoperative radiation was associated with dramatic reduction in tumor recurrence(18%vs 70%;P<0.001) and likelihood of neurologic deaths(14%vs 44%;P=0.003).
Overall survival,a secondary endpoint,showed no difference between the arms.
Comparison of surgery plus WBRT versus WBRT alone is discussed in the WBRT section.
In the case of multiple lesions,the role of surgery is more restricted to obtaining biopsy samples or relieving mass effect.
However,evidence from retrospective series suggested survival benefits from tumor resection for selected patients of good prognosis with up to three metastatic sites.224,225
Stereotactic radiosurgery
The advent of SRS offered a minimally invasive option as opposed to surgery.Patients undergoing SRS avoid the risk of surgery-related morbidity.
Late side effects such as edema and radiation necrosis are uncommon.226
SRS is mostly successful for small,deep tumors.
In a randomized Japanese study of 132 patients with 1 to 4 metastatic brain tumors smaller than 3 cm,addition of WBRT to SRS did not prolong median survival compared to SRS alone(7.5 months vs.8.0 months,respectively).227
However,1-year brain recurrence rate was lowered in the WBRT plus SRS arm(47%vs.76%;P<0.001).
This likely served to decrease the need for salvage therapy in this group (10/65)compared to patients receiving no upfront WBRT(29/67).
Retrospective comparative studies showed that SRS plus WBRT resulted in equivalent if not better survival compared with surgery and WBRT.228-230
SRS also conferred a significant improvement in local control,especially for patients with radiosensitive tumors or solitary brain lesions.
SRS alone compared to resection plus WBRT was evaluated in a randomized controlled trial by Muacevic et al.231
The study was stopped prematurely due to poor accrual.In the final analysis based on 64 patients with solitary brain
metastases,radiosurgery alone was less invasive and resulted in equivalent survival and local control, but it was associated with a higher rate of distant relapse.
Small patient series have demonstrated local control rates above 70% with SRS in the recurrence setting for patients with good performance status and stable disease who have received prior WBRT.232-236
Whole brain radiation therapy
Historically,WBRT was the mainstay of treatment for metastatic lesions in the brain.
It continues to play multiple roles in the modern era,as primary intervention where surgery or SRS are not feasible,as adjunctive therapy to prevent recurrence,and as treatment for recurrent disease.
Three randomized trials investigated the effectiveness of WBRT with or without surgery in patients with single brain metastases.
In a study of 48 patients,Patchell et al237 demonstrated that surgery followed by WBRT lengthened overall survival(40 vs.15 weeks in WBRT arm; P<0.01)and functional dependence(38 vs 8 weeks;P<0.005),as well as decreased recurrence(20%vs.52%;P<0.02)compared to radiation alone.
Similarly,combined treatment led to longer survival and functional independence in another randomized study by Vecht and colleagues(n=63).238
The greatest difference was observed in patients with stable disease;median survival was 12 months versus 7 months and functional independence was 9 months versus 4 months.
A third study of 84 patients found no difference in survival between the two strategies,however,patients with extensive systemic disease and lower performance level were included,which likely resulted in poorer outcomes in the surgical arm.239
The impact of SRS in addition to WBRT was evaluated in two randomized controlled studies.A multi-institutional trial by RTOG (RTOG 9508)randomly assigned 333 patients with 1 to 3 brain metastases to WBRT plus SRS or radiation only.240
Despite the inclusion of larger tumors(3-4 cm)that are not favorable to SRS,the authors found a significant survival benefit in the combined arm(6.5 vs. 4.9 months;P=0.04)when a single lesion was involved;this was not observed in patients with multiple lesions.
A much smaller trial of 27 patients with 2-4 lesions found no significant difference in survival, although SRS did extend time to local failure(36 vs.6 months; P=0.0005).241
Taken together,WBRT in conjunction with surgery or SRS leads to better clinical outcomes than WBRT alone for good
performance patients with solitary metastatic intracranial lesions.However,many patients are not candidates for resection because of the inaccessibility of the tumor,extensive systemic disease,or other factors.
WBRT is the main choice of primary therapy for this patient group.
No randomized data are available in the recurrent setting,but case series reported 31%to 70%of symptom-relieving response to irradiation.242-244
Systemic therapy
Systemic therapy is rarely used as primary therapy for brain metastases.
In randomized studies,addition of carboplatin or temozolomide to WBRT did not improve overall survival compared to radiation alone,245,246 although there have been reports of increase in progression-free survival or radiologic response with temozolomide.246,247
Many tumors that metastasize to the brain are not very chemosensitive or have been already heavily pretreated with potentially effective agents.
Poor penetration through the BBB is an additional concern.As such,chemotherapy is usually considered as a last line of therapy for recurrent disease when other options have been exhausted (surgery,SRS,radiation).
The choice of agent depends on the histology of the primary tumor.
Among various agents,temozolomide may be useful in some patients with previously untreated brain metastases from metastatic melanoma.248