Evaluation of 2 whole-brain radiotherapy schedules and prognostic factors for brain metastases in breast cancer patients

BACKGROUND: The majority of breast cancer patients with brain metastases receive whole-brain radiotherapy (WBRT) and have a survival of only a few months. A short WBRT regimen would be preferable if it provides survival that is similar to that achieved with longer programs. This retrospective study compared survival and local control within the brain resulting from short-course WBRT with longer programs in 207 breast cancer patients. METHODS: Sixty-nine patients treated with 5 fractions of 4 grays (Gy) each given within 5 days were compared with 138 patients treated with 10 fractions of 3 Gy each given over 2 weeks or 20 fractions of 2 Gy each given over 4 weeks. Six additional potential prognostic factors were investigated: age, Karnofsky performance score (KPS), number of brain metastases, the presence of extracranial metastases, interval from tumor diagnosis to WBRT, and recursive partitioning analysis (RPA) class. RESULTS: On univariate analysis, the WBRT regimen was not found to be associated with survival (P=.254) or local control (P=.397). Improved survival was associated with a KPS>70 (P<.001), single brain metastasis (P=.023), the absence of extracranial metastases (P<.001), and lower RPA class (P<.001). On multivariate analysis, which was performed without RPA class because this is a confounding variable, KPS (relative risk [RR] of 4.00; P<.001) and the presence of extracranial metastases (RR of 1.54; P=.024) maintained statistical significance. On univariate analysis, local control was associated with KPS (P<.001) and RPA class (P<.001). On multivariate analysis, local control was found to be associated with a KPS>70 (RR of 5.75; P<.001). CONCLUSIONS: Short-course WBRT with 5 fractions of 4 Gy each resulted in survival and local control that were similar to longer programs in breast cancer patients with brain metastases. The dose of 5 fractions of 4 Gy each appears preferable for the majority of these patients because it is less time consuming and more convenient.     

Two radiation regimens and prognostic factors for brain metastases in nonsmall cell lung cancer patients

BACKGROUND: Nonsmall cell lung cancer (NSCLC) patients with brain metastases usually receive whole-brain radiotherapy (WBRT). Most of these patients survive for only a few months. A short course of WBRT would be preferable to longer regimens if it could provide similar survival. This retrospective study of NSCLC patients compared longer treatment programs with short-course WBRT with 5 x 4 Gy given during 5 days. METHODS: Data from 404 NSCLC patients treated with WBRT for brain metastases were retrospectively analyzed. The 140 patients who received 5 x 4 Gy given in 5 days were compared for survival with 264 patients who received either 10 x 3 Gy given in 2 weeks or 20 x 2 Gy given in 4 weeks. Seven further potential prognostic factors were investigated for survival including age, sex, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, interval from tumor diagnosis to WBRT, and RPA (recursive partitioning analysis) class. RESULTS: The WBRT regimen was not associated with survival (P = .55). On multivariate analysis, age < 60 years (vs > or =60 years, P = .020), KPS > or =70 (vs KPS < 70, P < .001), interval from tumor diagnosis to WBRT > 12 months (vs < or =12 months, P = .007), no extracranial metastases (P < .001), and RPA class 1 (vs RPA class 2 vs RPA class 3, P = .007) were significantly associated with improved survival. CONCLUSIONS: Short-course WBRT with 5 x 4 Gy appeared preferable for most NSCLC patients, as it was associated with survival similar to longer WBRT programs, and the short course was less time consuming.     

A boost in addition to whole-brain radiotherapy improves patient outcome after resection of 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients

BACKGROUND: The current study was conducted to compare 2 treatment regimens including surgical resection and whole-brain radiotherapy (WBRT) for patients with 1 to 2 brain metastases. METHODS: A total of 201 patients with recursive partitioning analysis (RPA) class 1 to 2 disease with 1 to 2 resectable brain metastases were analyzed retrospectively. Patients underwent either resection of the metastases plus WBRT with 10 fractions of 3 grays (Gy) each or 20 fractions of 2 Gy each (99 patients; Group A) or the same treatment plus a WBRT boost to the metastatic site (10 fractions of 3 Gy each plus 5 fractions of 3 Gy each or 20 fractions of 2 Gy each plus 5 fractions of 2 Gy each) (102 patients; Group B). Eight other potential prognostic factors were evaluated with regard to overall survival (OS), brain control (BC), and local control of resected metastases (LC): age, gender, Karnofsky performance status, extent of surgical resection, tumor type, extracranial metastases, RPA class, and interval from tumor diagnosis to WBRT. RESULTS: Group B patients had better 1-year OS (66% vs 41%; P < .001). On multivariate analysis of OS, treatment regimen (relative risk [RR] of 1.94; P < .001), extent of surgical resection (RR of 1.80; P = .001), and interval from tumor diagnosis to WBRT (RR of 1.62; P = .010) were found to be statistically significant. On multivariate analysis of BC, treatment regimen (RR of 2.15; P = .002), extent of surgical resection (RR of 2.78; P < .001), and interval from tumor diagnosis to WBRT (RR of 1.52; P = .034) were found to be statistically significant. On multivariate analysis of LC, treatment regimen (RR of 2.31; P = .002) and extent of surgical resection (RR of 3.79; P < .001) were found to be statistically significant. On RPA class subgroup analyses, outcome was found to be significantly better with a WBRT boost in both RPA class 1 and class 2 patients. A WBRT boost resulted in better outcome after both complete and incomplete surgical resection. However, the results concerning BC and LC were not found to be statistically significant if surgical resection was incomplete. CONCLUSIONS: After surgical resection of 1 to 2 brain metastases, a boost of 10 to 15 Gy in addition to WBRT was found to improve outcome. After incomplete surgical resection, further dose escalation to the metastatic site may be considered.     

Whole-brain radiotherapy versus stereotactic radiosurgery for patients in recursive partitioning analysis classes 1 and 2 with 1 to 3 brain metastases

BACKGROUND: The authors investigated whether stereotactic radiosurgery (SRS) alone improved outcomes for patients in recursive partitioning analysis (RPA) Classes 1 and 2 who had 1 to 3 brain metastases compared with whole-brain radiotherapy (WBRT). METHODS: Data regarding 186 patients in RPA Classes 1 and 2 who had 1 to 3 brain metastases and who received either 30 to 40 grays (Gy) of WBRT (n = 91 patients) or 18 to 25 Gy SRS (n = 95 patients) were analyzed retrospectively. Eight other potential prognostic factors were evaluated regarding overall survival (OS), entire brain control (BC), local control (LC) of treated metastases, and brain control distant from treated metastases (distant control [DC]): Those 8 factors were age, sex, performance status, tumor type, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to radiotherapy. RESULTS: On multivariate analysis of OS, age ( risk ratio [RR], 1.51; P = .024), Karnofsky performance status (KPS) (RR, 1.98; P = .002), and extracranial metastases (RR, 2.26; P < .001) were significant, whereas the radiation regimen was not significant (P = .89). On multivariate analysis of BC, only the radiation regimen (RR, 1.33; P = .003) was found to be significant. On multivariate analysis of LC, radiation regimen (RR, 1.63; P < .001) and sex (RR, 1.62; P = .022) were significant. On multivariate analysis of DC, KPS (RR, 1.85; P = .049) and extracranial metastases (RR, 1.69; P = .047) were significant. The radiation regimen was not found to be significant even on univariate analysis (P = .80). In RPA class subgroup analyses, BC and LC were better after SRS than WBRT for patients in RPA Classes 1 and 2, whereas OS and DC did not differ significantly. CONCLUSIONS: For patients in RPA Classes 1 and 2 who had 1 to 3 brain metastases, SRS alone was associated with improved BC and LC compared with 30 to 40 Gy WBRT, whereas OS and DC were not significantly different. Similar results were observed in separate subgroup analyses of patients in RPA Class 1 and RPA Class 2.     

Stereotactic radiosurgery alone versus resection plus whole-brain radiotherapy for 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients

BACKGROUND: The objective of this study was to compare stereotactic radiosurgery (SRS) alone with resection plus whole-brain radiotherapy (WBRT) for the treatment of patients in recursive partitioning analysis (RPA) class 1 and 2 who had 1 or 2 brain metastases. METHODS: Two hundred six patients in RPA class 1 and 2 who had 1 or 2 brain metastases were analyzed retrospectively. Patients in Group A (n = 94) received from 18 grays (Gy) to 25 Gy SRS, and patients in Group B (n = 112) underwent resection of their metastases and received 10 x 3 Gy/20 x 2 Gy WBRT. Eight other potential prognostic factors were evaluated regarding overall survival (OS), brain control (BC), and local control (LC) of treated metastases: age, sex, performance status, tumor type, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to treatment of brain metastases. RESULTS: A comparison of the 2 treatment groups did not reveal significantly different OS (P = .19), BC (P = .52), or LC (P = .25). In RPA subgroup analyses, outcome also did not differ significantly for either RPA class of patients (P values from .21 to .83). On multivariate analysis, improved OS was associated with age < or =60 years (relative risk [RR], 1.75; P = .002), better performance status (RR, 1.67; P = .015), no extracranial metastases (RR, 2.84; P < .001), interval from tumor diagnosis to treatment >12 months (RR, 1.70; P = .003), and RPA class 1 (RR, 1.51; P = .016). Improved BC was associated with a single metastasis (RR, 1.54; P = .034) and an interval from tumor diagnosis to treatment >12 months (RR, 1.58; P = .019), and improved LC was associated with an interval from tumor diagnosis to treatment >12 months (RR, 1.59; P = .047). CONCLUSIONS: SRS alone appeared to be as effective as resection plus WBRT in the treatment of 1 or 2 brain metastases for patients in RPA class 1 and 2. Patient outcomes were associated with age, Karnofsky performance status, number of brain metastases, extracranial metastases, RPA class, and interval from tumor diagnosis to treatment.     

Reduction of overall treatment time in patients irradiated for more than three brain metastases

PURPOSE: Patients with multiple brain metastases usually receive whole brain radiotherapy (WBRT). A dose of 30 Gy in 10 fractions (10 x 3 Gy) in 2 weeks is the standard treatment in many centers. Regarding the poor survival of these patients, a shorter RT regimen would be preferable if it provides a similar outcome as that with 10 x 3 Gy. This study compared 20 Gy in five fractions (5 x 4 Gy) within 5 days to 10 x 3 Gy. METHODS AND MATERIALS: Data from 442 patients treated with WBRT for multiple brain metastases were retrospectively analyzed. Survival and local control within the brain of 232 patients treated with 5 x 4 Gy were compared with the survival and local control within the brain of 210 patients treated with 10 x 3 Gy. Seven additional potential prognostic factors were investigated: age, gender, Karnofsky performance score, tumor type, interval from tumor diagnosis to RT, extracranial metastases, and recursive partitioning analysis class. RESULTS: On univariate analysis, the WBRT program was not associated with survival (p = 0.29) or local control (p = 0.07). On multivariate analyses, improved survival was associated with a lower recursive partitioning analysis class (p < 0.001), age or=70 (p = 0.015), and the absence of extracranial metastases (p = 0.005). Improved local control was associated with a lower recursive partitioning analysis class (p < 0.001), Karnofsky performance score >or=70 (p < 0.001), and breast cancer (p = 0.043). Grade 3 acute toxicity rates were not significantly different between 5 x 4 Gy and 10 x 3 Gy. CONCLUSIONS: Shorter course WBRT with 5 x 4 Gy was associated with similar survival and local control as "standard" WBRT with 10 x 3 Gy in patients with more than three brain metastases. The 5 x 4-Gy regimen appears preferable for most of these patients, because it is less time consuming and more convenient for patients than the 10 x 3-Gy regimen.     

A prognostic index that predicts outcome following palliative whole brain radiotherapy for patients with metastatic malignant melanoma

To determine the outcome of patients with metastatic malignant melanoma (MMM) treated with palliative whole brain radiotherapy (WBRT) and to identify factors that predict treatment outcome to assist future trial design, a retrospective study was performed on patients with MMM who received WBRT at the Royal Marsden Hospital between 1998 and 2003. Data regarding patient factors, tumour factors and survival were collected. A total of 112 patients were identified and full data were available for 102 patients. The median age was 53 years (range 25-81 years), 66.7% were male and 33.3% female. The median dose prescribed was 20 Gy in five fractions as a mid-plane dose. The median survival after WBRT for the whole group was 51 days (range 3-1386). In an attempt to define prognostic groups, we used the validated RTOG recursive partitioning analysis (RPA) classification for brain metastasis (class 1: Karnofsky Performance Score (KPS) >/=70%, age <65 years with no extracranial metastasis; class 3: KPS <70%; class 2: all others). The median survivals were 151, 71 and 21 days for RPA class 1, 2 and 3, respectively (P<0.001). Multivariate analysis showed that RPA class, leptomeningeal involvement, presence and number of extracranial metastatic sites and progressive disease in the brain on imaging before WBRT are important independent predictive factors. A prognostic index was derived from these factors that allowed identification of patients unlikely to benefit from WBRT. In conclusion, the RTOG RPA classification is valid when applied to patients with MMM. Patients in RPA class 1 and good prognosis class 2 are likely to benefit from palliative WBRT and should be considered for entry into trials that aim to improve duration of response. We identified that patients with RPA class 3, leptomeningeal involvement or RPA class 2 with poor prognostic index are unlikely to benefit from palliative WBRT.     

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

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

乳腺癌脑转移全脑放疗预后及预后指数分析

目的 探讨乳腺癌脑转移患者全脑放疗(WBRT)预后以及不同预后指数差别。
方法 对2006-2010年间接受WBRT的99例乳腺癌脑转移患者进行Logrank法单因素与Cox法多因素预后分析,计算并比较RPA、GPA、BSBM、Rades、Carsten预后指数评分的敏感性和特异性。
结果 全组患者中位随访时间49个月,中位生存期为10个月。单因素分析显示年龄、脑转移时卡氏评分、是否伴有颅外转移、原发肿瘤控制情况、脑转移数目和WBRT后全身治疗与总生存相关(χ²=0.00~55.51,P=0.013~0.000),多因素分析证实卡氏评分<70和WBRT后全身治疗与总生存相关(χ²=35.26、7.21,P=0.000、0.007)。RPA、GPA、BSBM、Rades、Carsten预后指数评分对预测生存期≤3个月乳腺癌脑转移患者的敏感性和特异性分别为100%和85%、95%和62%、95%和86%、95%和84%、95%和85%。
结论 乳腺癌脑转移患者WBRT后全身治疗可改善患者总生存。对预测生存期≤3个月患者敏感性最好的为RPA指数,特异性最好的为BSBM指数。     

非小细胞肺癌脑转移患者全脑放疗不同剂量预后分析

目的:分析非小细胞肺癌(NSCLC)脑转移患者不同全脑放疗(WBRT)剂量的预后及影响因素。方法:回顾性分析2013—2015年间于河北医科大学第四医院行WBRT的244例NSCLC脑转移患者。按照不同WBRT剂量(EQD 2Gy)分为30~39 Gy组104例、≥40 Gy组140例。比较两组患者颅内无进...     

Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases

PURPOSE: To evaluate the usefulness of whole brain radiotherapy (WBRT) and of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) for brain metastases among patients receiving stereotactic radiosurgery (SRS). METHODS AND MATERIALS: A retrospective analysis was performed on 135 patients who underwent linear accelerator (Linac) (n = 73) or Gamma Knife (n = 62) SRS for newly diagnosed brain metastases at the Cleveland Clinic Foundation between 8/89 and 12/98. Univariate and multivariate analyses were performed to evaluate the effects of age, primary site, control of the primary, interval to development of brain metastases (disease-free interval [DFI]), number of brain metastases, presence of extracranial metastases, Karnofsky performance status (KPS), treatment of brain metastases, and RPA class on overall survival. RESULTS: Application of the RPA classification revealed 29 patients fit the criteria for class I, 96 for class II, and 10 for class III. All of the patients underwent SRS. Fifty-seven patients also received WBRT at the time of initial presentation (SRS and immediate WBRT), and 78 patients received WBRT only if CNS relapse occurred (SRS alone). The median survival for all patients was 7.9 months (range: 1.1-90.1), and was 11.2 months for RPA class I compared to 6. 9 months for RPA classes II-III (p = 0.016). Median survival was 10. 5 months following SRS alone compared to 6.4 months following SRS and WBRT (p = 0.07). On univariate analysis, KPS >/= 80% (p = 0.002) and absence of systemic disease (p = 0.013) were also associated with longer survival, whereas control of the primary, DFI, and number of brain metastases did not have an impact. Multivariate analysis revealed only RPA class (p = 0.023) to be an independent predictor for overall survival, whereas treatment group (p = 0.079) was only marginally significant. At 2 years, immediate WBRT improved control at the original site of metastases (80% vs. 52%, p = 0.03) and prevention of new metastatic sites within the brain, 74% vs. 48% (p = 0.06). The 2-year intracranial disease-free survival was 60% following SRS and WBRT compared to only 34% following SRS alone (p = 0.03). CONCLUSIONS: Despite the inherent biases to select more favorable patients for SRS, the RPA class retains its prognostic value. Omission of WBRT from the initial management was not detrimental in terms of overall survival; however, progressive disease occurred in over 50% of patients treated in this manner. Further studies are required to determine which, if any, patients should be considered for SRS with WBRT held in reserve.     

立体定向放疗与全脑放疗在多发脑转移瘤治疗中的作用分析

目的 总结立体定向放疗(SRT)加或不加全脑放疗(WBRT)治疗多发脑转移瘤的结果,探讨WBRT和SRT在多发脑转移瘤治疗中的作用。方法 1995—2010年收治的98例新诊断的多发(2~13个病灶)脑转移瘤患者。单纯SRT44例,WBRT加SRT54例。剂量分割模式依据转移瘤部位、体积及是否WBRT。用Kaplan-Meier法计算生存率,Cox回归模型进行各因素预后分析。中位生存期(MST)为从脑转移瘤放疗开始至各种原因所致死亡的时间的中位数。结果 全组患者中位随访时间12个月,随访率为100%。全组MST为13.5个月,其中SRT组、WBRT加SRT组的分别为13.0、13.5个月(χ²=0.31,P=0.578)。多因素分析显示仅卡氏评分(χ²=6.25,P=0.012)、原发灶诊断及脑转移瘤诊断间隔时间(χ²=7.34,P=0.025)和颅外病变情况(χ²=4.20,P=0.040)是预后因素。结论 SRT是多发脑转移瘤患者有效治疗手段,单纯SRT可取得与WBRT加SRT相似的生存期。首程SRT可能是多发脑转移瘤患者的另一治疗选择。     

Initial treatment of melanoma brain metastases using gamma knife radiosurgery: an evaluation of efficacy and toxicity

BACKGROUND: Melanoma is the primary malignancy that is most likely to metastasize to the brain. Because such an event carries an almost uniformly poor prognosis, the current study reviewed outcomes and identified associated prognostic indicators for 51 consecutive patients receiving gamma knife (GK) radiosurgery in the initial treatment of 188 intracranial melanoma metastases. METHODS: Data were collected retrospectively from a single-center GK radiosurgery database and from primary patient medical records and radiographs. RESULTS: At presentation, 71% of patients had multiple intracranial metastases, and extracranial metastases were present in 66% of patients. Thirty-two patients (63%) were initially treated with GK radiosurgery alone, whereas the remainder received GK radiosurgery in combination with surgery and/or whole-brain radiotherapy (WBRT). Overall median survival from time of GK radiosurgery was 26 weeks. Subgroup analysis revealed a median survival of 77 weeks for patients presenting with a single lesion, compared with 20 weeks for patients presenting with multiple lesions (P = 0.003). Patients in recursive partitioning analysis (RPA) Class I survived a median of 57 weeks, compared with a median survival of 20 weeks for patients in RPA Class II or III (P = 0.002). Although long-term imaging follow-up revealed that a majority of patients experienced distant brain metastases, multivariate analysis showed that distant metastases occurred significantly sooner in patients with extracranial metastases (P = 0.0004). Addition of initial WBRT had no significant effect on the time to development of new brain metastases (P = 0.13). Local control (crude) was observed in 81% of lesions initially treated with GK. Patients experienced improved or stable symptoms for a median of 37 weeks post-GK radiosurgery. CONCLUSIONS: Survival analyses supported the use of GK radiosurgery in the initial treatment of patients with melanoma brain metastases, with best results occurring in patients presenting with a single lesion.     

不同EGFR突变肺腺癌脑转移患者WBRT分析

目的 探讨肺腺癌脑转移患者不同EGFR突变状态WBRT疗效差别。方法 回顾分析2010—2015年在本院诊治的89例肺腺癌脑转移患者,所有患者均行EGFR检测。脑转移一线6 MV X线外照射:WBRT30 Gy分10次或40 Gy分20次(≤3个脑转移灶IMRT同步加量40~45 Gy分10次或50~60 Gy分20次)。比较EGFR突变和野生型患者的有效率、IPFS、OS。Kaplan-Meier法计算IPFS、OS并Logrank检验和单因素分析,Cox模型多因素分析。结果 89例患者总有效率为62%,中位IPFS为7.0个月(95%CI为6.060~7.940),中位OS为12.0个月(95%CI为9.539~14.465)。单因素和多因素分析结果显示脑转移患者有效率与KPS评分、EGFR突变状态相关(P=0.009、0.035),KPS评分、EGFR突变状态是IPFS的影响因素(P=0.048、0.000),KPS评分、原发灶控制是OS的影响因素(P=0.000、0.031)。结论 肺腺癌脑转移患者WBRT后,EGFR突变较野生型有效率高,IPFS时间长,OS无差别。     

Whole brain irradiation and temozolomide based chemotherapy in melanoma brain metastases

Introduction Whole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma in terms of symptom palliation, especially when extracranial systemic disease is present. Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma. The objective was to evaluate the potential benefit in survival of two different schedules of total dose and fractionation (20 Gy/5 fractions vs 30 Gy/10 fractions) and further TMZ based chemotherapy. Materials and method We have conducted a retrospective study in a group of twenty-one patients (RTOG Recursive Partitioning Analysis class II) of the use of WBRT with 20 Gy/5 fractions (n=11) and 30 Gy/10 fractions (n=10). All patients received further TMZ based chemotherapy administered as a single chemotherapeutic agent or in combination with chemo-immunotherapy. Results Prognostic variables such as: age, Karnofsky performance status, extracranial metastases and number of brain metastases, were analyzed in both groups of treatment without statistically significant differences. The median survival time (MST) for WBRT 20 Gy group was 4 months (CI 95%: range 2–6 months) and for WBRT 30 Gy group was 4 months (CI 95%: range 0–7 months) without statistically significant differences (Log rank p=0.74). There was one complete response and two partial responses. Conclusions The results suggest that MST was not significantly affected by the total dose/fractionation schedule.     

脑转移瘤放射治疗的预后因素分析及预后模型的建立

背景与目的：放射治疗是大多数脑转移瘤最主要的治疗手段,而预后却受多种因素的影响。本研究探讨影响肿瘤脑转移患者放射治疗生存期的预后因素并建立预后指数模型。方法：选择2008年1月—2011年7月符合入组条件接受放射治疗的脑转移患者140例,对各影响因素行单因素分析,差异有统计学意义的因素再行多因素分析,筛选出与预后最为相关的因素,并计算预后指数(prognostic index,PI)。同时,评估递归分区分析(recursive partitioning analysis classes,RPA)、脑转移基本评分(basic score for brain metastases,BS-BM)及等级预后评估标准(the graded prognostic assessment index,GPA)是否与预后相关。结果：全组中位生存时间为222 d。单因素检验提示卡氏评分(karnofsky performance score,KPS)、脑转移数目、中枢外转移、原发灶控制、放疗剂量、血红蛋白与预后相关;多因素分析筛选出KPS(P=0.002、Wald=9.700)、中枢外转移(P=0.018,Wald=5.604)、原发灶控制(P=0.001、Wald=10.212)3个因素影响总生存期。Log-rank检验提示,3种评分模式均与预后相关,而对于本组患者的3、6个月生存概率的预测,PI优于其他评分模式。结论：PI预后指数模型和3种预后指数均能反映预后,但PI更佳。     

Brain Metastases in Patients with Cancer of Unknown Primary

Between January 1985 and December 2000, 916 patients with brain metastases were treated with whole brain radiation therapy (WBRT) at the Department of Radiotherapy, University Hospital Freiburg. In 47 patients, a primary tumor could not be identified (cancer of unknown primary (CUP)). Sixteen patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 15 patients, biopsy alone in 12 patients. WBRT was applied with daily fractions of 2 or 3Gy to a total dose of 50 or 30Gy, respectively. According to the recursive partitioning analysis (RPA) classes of the Radiation Therapy Oncology Group for patients with brain metastases none of the patients met the criteria for Class I, 23 for Class II, and 24 for Class III.The median overall survival (OS) for all patients with brain metastases (n = 916) was 3.4 and 4.8 months for patients with CUP (p = 0.45). In patients with CUP (n = 47) the median OS for patients with a single brain metastasis was 7.3 versus 3.9 months for patients with multiple brain metastases (p = 0.05). Median OS for patients with a Karnofsky performance status (KPS) 70 was 6.3 months versus 3.2 months for KPS <70 (p = 0.01).At multivariate analysis performance status and resection status could be identified as independent prognostic factors for the OS.     

The efficacy of gamma knife radiosurgery for advanced gastric cancer with brain metastases

The aim of this study was to retrospectively investigate the efficacy of gamma knife radiosurgery for brain metastases from advanced gastric cancer (AGC) comparing whole brain radiotherapy (WBRT). Between January 1991 and May 2008, 56 patients with brain metastases from AGC, treated with GKR or WBRT, were reviewed to assess prognostic factors affecting survival. Most brain metastases were diagnosed based on MRI, both metachronous and synchronous brain metastases, adenocarcinoma and signet ring carcinoma were included, but excluded cases of gastric lymphoma. Fifteen patients with a median age of 54.0 years (range, 42–67 years) were treated with GKR: 11 were treated with GKR only, 2 with surgery plus GKR, 1 with repeated GKR, 1 with GKR plus WBRT, and the other 1 with WBRT plus GKR. Forty-one were treated with WBRT only. The median number of metastatic brain lesions was 3 (range, 1–15), and treatment involved 17.0 Gy (range 14–23.6 Gy), or 30 Gy with fractionated radiotherapy. The median survival after brain metastases for GKR treatment was 40.0 weeks [95% confidence interval (CI) 44.9–132.1 weeks] and WBRT was 9.0 weeks 95% CI, 8.8–21.9 weeks). The progression free survival of 15 GKR treated patients was 56.5 weeks (95% CI 33.4–79.5 weeks). The recursive partitioning analysis (RPA) (class 2 vs. class 3) and use of GKR were correlated with prolonged survival in univariate and multivariate analyses. Age, sex, pathology, leptomeningeal seeding, tumor size (≥3 cm), extracranial metastases, single metastasis, chemotherapy, and synchronous metastases were not correlated with a good prognosis in both univariate and multivariate analysis. Based on our study, the use of GKR and RPA class 2 resulted in more favorable clinical outcomes in patients with brain metastases from AGC.     

Selection of patients with melanoma brain metastases for aggressive treatment

The purpose of this study was to determine prognostic factors for patients with melanoma brain metastases that can be recommended for patient selection for clinical trials. A retrospective review was conducted of 65 patients irradiated for brain metastases from 1990 to 1997. Pretreatment factors analyzed for influence on survival included age, stage, Karnofsky Performance Status (KPS), extracranial metastases, the number and location of brain lesions, disease-free interval from initial diagnosis, total dose of radiation, and number of fractions administered. Prognosis was also analyzed by Radiation Therapy Oncology Group recursive partitioning analyses (RPA) classes. The data were analyzed using the Kaplan-Meier method. Median survival was 4 months. RPA class distribution was I-25%, II-48%, and III-28% with a median survival of 6.5, 3.5, and 2.5 months, respectively (p = 0.0098 by log-rank test). KPS less than 70% (p = 0.0039), and the presence of extracranial metastases (p = 0.03), predicted a worse prognosis on univariate analysis. Both factors remained significant on multivariate analysis. The prognosis of patients receiving radiotherapy for brain metastases is related to RPA class, the presence of extracranial metastases, and KPS. These criteria should be employed in selecting patients for aggressive protocol treatment, or for more protracted brain irradiation off protocol.     

Prognostic factors in brain metastases: should patients be selected for aggressive treatment according to recursive partitioning analysis (RPA) classes?

PURPOSE: To determine whether or not Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) derived prognostic classes for patients with brain metastases are generally applicable and can be recommended as rational strategy for patient selection for future clinical trials. Inclusion of time to non-CNS death as additional endpoint besides death from any cause might result in further valuable information, as survival limitation due to uncontrolled extracranial disease can be explored. METHODS: We performed a retrospective analysis of prognostic factors for survival and time to non-CNS death in 528 patients treated at a single institution with radiotherapy or surgery plus radiotherapy for brain metastases. For this purpose, patients were divided into groups with Karnofsky performance status (KPS) <70% and KPS > or =70%, as proposed by the RTOG. RESULTS: Median overall survival was 2.9 months (2.0 months for patients with KPS <70% and 3.6 months for patients with KPS > or =70%, p < 0.001). We did not find other variables splitting patients with KPS <70% in different prognostic groups. However, advanced age, multiple brain metastases, presence of extracranial metastases, and uncontrolled primary tumor each predicted shorter survival in patients with KPS > or =70%. When grouped into the original RTOG RPA classes, our data set split into three subgroups with different prognosis and median survival times of 10.5, 3.5, and 2 months, respectively (p < 0.05). Only 3% of patients fell into the most favorable group. Median time to non-CNS death was 4.1 months (12.9 months in RPA class I, 4.9 months in RPA class II, and 3.8 months in RPA class III, respectively, p > 0.05 for RPA class II versus III). However, it was 8.5 months in RPA class II patients with controlled primary tumor, which was found to be the only prognostic factor for time to non-CNS death in patients with KPS > or =70%. In patients with KPS <70%, no statistically significant prognostic factors were identified for this endpoint. CONCLUSIONS: Despite some differences, this analysis essentially confirmed the value of RPA-derived prognostic classes, as published by the RTOG, when survival was chosen as endpoint. RPA class I patients seem to be most likely to profit from aggressive treatment strategies and should be included in appropriate clinical trials. However, their number appears to be very limited. Considering time to non-CNS death, our results suggest that certain patients in RPA class II also might benefit from increased local control of brain metastases.