Systemic treatment after whole-brain radiotherapy may improve survival in RPA class II/III breast cancer patients with brain metastasis

Whole brain radiotherapy (WBRT) is the most widely used treatment for brain metastasis (BM), especially for patients with multiple intracranial lesions. The purpose of this study was to examine the efficacy of systemic treatments following WBRT in breast cancer patients with BM who had different clinical characteristics, based on the classification of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) and the breast cancer-specific Graded Prognostic Assessment (Breast-GPA). One hundred and one breast cancer patients with BM treated between 2006 and 2010 were analyzed. The median interval between breast cancer diagnosis and identification of BM in the triple-negative patients was shorter than in the luminal A subtype (26 vs. 36 months, respectively; P = 0.021). Univariate analysis indicated that age at BM diagnosis, Karnofsky performance status/recursive partitioning analysis (KPS/RPA) classes, number of BMs, primary tumor control, extracranial metastases and systemic treatment following WBRT were significant prognostic factors for overall survival (OS) (P < 0.05). Multivariate analysis revealed that KPS/RPA classes and systemic treatments following WBRT remained the significant prognostic factors for OS. For RPA class I, the median survival with and without systemic treatments following WBRT was 25 and 22 months, respectively (P = 0.819), while for RPA class II/III systemic treatments significantly improved OS from 7 and 2 months to 11 and 5 months, respectively (P < 0.05). Our results suggested that triple-negative patients had a shorter interval between initial diagnosis and the development of BM than luminal A patients. Systemic treatments following WBRT improved the survival of RPA class II/III 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。     

Brain metastases in patients who receive trastuzumab-containing chemotherapy for HER2-overexpressing metastatic breast cancer

Background  Recently, a high rate of brain metastases has been reported among patients with human epidermal growth factor receptor (HER2)-overexpressing metastatic breast cancer who were treated with trastuzumab. The present study examined risk factors for the development of brain metastasis in patients with HER2-overexpressing breast cancer who were treated with trastuzumab. Methods  We retrospectively reviewed 204 patients with HER-2-overexpressing breast cancer who were treated with a trastuzumab-containing regimen between 1999 and 2006. Patients with clinical symptoms were diagnosed as having brain metastases when brain magnetic resonance imaging (MRI) or a computed tomography (CT) scan revealed positive findings for brain metastases. The median follow-up time of this cohort was 53.6 months. Results  Among the patients who received a trastuzumabcontaining regimen, 74 patients (36.3%) developed brain metastases. The median survival from the diagnosis of brain metastases was 13.5 months (95% confidence interval [CI], 12.2–14.7 months). The median time interval between the beginning of trastuzumab treatment and the diagnosis of brain metastases was 13.6 months (range, 0.0–45.8 months). Among patients with brain metastases, the median overall survival period was 39 months. A multivariate logistic regression analysis showed that age (≤50 years), recurrent breast cancer, and liver metastases were significant risk factors for the development of brain metastases. Conclusion  Patients with HER2-overexpressing breast cancer treated with trastuzumab had a high incidence of brain metastases (36.3%). Routine screening for brain metastases 1 year after the start of trastuzumab treatment, may be warranted in younger patients (≤50 years) who had recurrent breast cancer with liver metastases.     

288例非小细胞肺癌脑转移全脑放射治疗的预后因素分析

[目的]分析影响接受全脑放射治疗的非小细胞肺癌脑转移患者的预后因素;对比评估RPA和GPA两种预后指数对临床及研究的指导意义。[方法]回顾性分析2006年1月～2008年8月在我科接受全脑放射治疗的288例非小细胞肺癌脑转移患者的临床资料,以Kaplan—Meier法计算生存率．采用多因素Cox回归法分析影响生存预后的各种因素。根据RPA和GPA两种预后指数分别建立预后模型,并分析模型中各亚组生存曲线的差异,各亚组生存率差异的比较采用Log-Rank检验。[结果]各组患者随访时间为1-33个月,其中接受全脑放射治疗后的中位生存期为8个月（95％CI：7．07～8．92个月）。多因素分析显示放射治疗前的KPS评分、原发肿瘤控制情况、年龄、脑转移灶数目、颅外转移情况、分子靶向药物治疗情况是影响生存率的独立预后因素。根据RPA和GPA指数建立的预后模型,各亚组生存曲线的差异均有统计学意义（P〈0．001）。[结论]KPS评分、原发肿瘤控制情况、年龄、脑转移灶数目、颅外转移情况、分子靶向药物治疗情况是影响非小细胞肺癌脑转移全脑放射治疗生存率的独立预后因素．RPA和GPA两种预后指数模型均能较好地反映预后。     

伽玛刀治疗肺癌脑转移瘤生存与预后分析

目的:分析伽玛刀治疗肺癌脑转移瘤患者的生存及预后影响因素。方法:回顾性分析行伽玛刀治疗的56例肺癌脑转移瘤患者,单纯SRS组22例,单纯SRT组16例,联合全脑放疗(WBRT)组9例,行伽玛刀挽救组7例,行联合WBRT挽救组2例。Log rank法单因素分析影响预后的因素。结果:全组经治疗后6月、1年生存率分别为50%、10%,中位生存期为6个月。单纯SRS、单纯SRT、SRS联合WBRT、SRS/SRT挽救组、SRS+WBRT挽救组6月生存率分别为59%、55%、40%、33%、0%,中位生存期分别为8、9、6、5、3个月（P=0.005）。其中,SRS对SRT（P=0.157）、SRS对SRS+WBRT（P=0.551）、SRT对SRS+WBRT（P=0.266）、SRS/SRT挽救组对SRS+WBRT挽救组（P=0.177）无统计学意义。单因素分析显示影响总生存率的因素有原发灶的控制情况、病理、中枢外转移情况、KPS评分、RPA分级、病灶所处位置、前期化疗、前期颅内治疗、病灶数目(P=0.000、0.013、0.002、0.000、0.000、0.000、0.043、0.011、0.037)。多因素分析显示KPS评分、原发灶控制、病理、前期颅内处理影响生存（P=0.000、0.005、0.006、0.002）。结论:用伽玛刀行单次SRS或分次SRT或与WBRT联合治疗在对生存获益上相似;KPS评分、原发灶控制情况、病理类型、前期颅内处理是影响生存的主要因素。     

Brain metastases from breast carcinoma: validation of the radiation therapy oncology group recursive partitioning analysis classification and proposition of a new prognostic score

PURPOSE: To validate the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification and determine independent prognostic factors, to create a simple and specific prognostic score for patients with brain metastases (BM) from breast carcinoma treated with whole-brain radiotherapy (WBRT). METHODS AND MATERIALS: From January 1998 through December 2003, 132 patients with BM from breast carcinoma were treated with WBRT. We analyzed several potential predictors of survival after WBRT: age, Karnofsky performance status, RTOG-RPA class, number of BM, presence and site of other systemic metastases, interval between primary tumor and BM, tumor hormone receptor (HR) status, lymphocyte count, and HER-2 overexpression. RESULTS: A total of 117 patients received exclusive WBRT and were analyzed. Median survival with BM was 5 months. One-year and 2-year survival rates were 27.6% (95% confidence interval [CI] 19.9-36.8%) and 12% (95% CI 6.5-21.2%), respectively. In multivariate analysis, RTOG RPA Class III, lymphopenia (< or =0.7 x 10(9)/L) and HR negative status were independent prognostic factors for poor survival. We constructed a three-factor prognostic scoring system that predicts 6-month and 1-year rates of overall survival in the range of 76.1-29.5% (p = 0.00033) and 60.9-15.9% (p = 0.0011), respectively, with median survival of 15 months, 5 months, or 3 months for patients with none, one, or more than one adverse prognostic factor(s), respectively. CONCLUSIONS: This study confirms the prognostic value of the RTOG RPA classification, lymphopenia, and tumor HR status, which can be used to form a prognostic score for patients with BM from breast carcinoma.     

Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

The aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive triple-negative breast cancer patients with brain metastases treated in the years 2003–2009 was performed. In 75 patients, immunohistochemistry was used as a surrogate of microarray in order to evaluate the expression of three basal markers: cytokeratin 5/6 (CK 5/6), EGFR/HER1 and c-KIT. The basal-like (ER/PgR/HER2-negative, CK5/6positive and/or HER1-positive) and non-basal-like (ER/PgR/HER2-negative, CK5/6-negative, HER1-negative) subsets were selected. Clinical features and survivals were compared in both groups. In the group of 111 triple-negative breast cancer patients, median DFS, OS and survival from brain metastases were 20, 29 and 4 months, respectively. In 75 patients who were evaluable for basal markers, median DFS, OS and survival from brain metastases were 18, 26 and 3.2 months, respectively. In the basal-like subtype, the survival rates were 15, 26 and 3 months, respectively, and in the non-basal-like subtypes, they were 20, 30 and 2.8 months, respectively. No statistically significant differences in survivals were detected between the basal-like and non-basal-like biological subtypes. Factors influencing survival from brain metastases were: Karnofsky performance status (KPS), the status of extracranial disease and age. Biological markers differentiating triple-negative group into basal-like and non-basal-like subtype (CK 5/6, HER1, c-KIT) had no influence on survival. In patients with triple-negative breast cancer and brain metastases, well-known clinical, but not molecular, features correlated with survival.     

Brain metastases from colorectal carcinoma: prognostic factors and outcome

Brain metastases from colorectal carcinoma (CRC) are rare. The objectives of this study are to assess the natural history, outcome, and possible prognostic factors in CRC patients with brain metastases. Between 1995 and 2008, 8,732 patients with CRC were treated at Yonsei University Health System. Brain metastases were found in 1.4% of these patients. Retrospective review and statistical analysis of these 126 patients were performed. Median time from diagnosis of metastatic CRC (mCRC) to brain metastases was 9.0 months (range 0–85 months), and 14 patients (11.1%) had brain involvement as their initial presentation. Among the 126 patients, 91.3% had other systemic metastases; the most common extracranial metastatic site was lung (72.2%). Median follow-up duration was 6.1 months (range 0.1–90.3 months), and median survival after diagnosis of brain metastases was 5.4 months [95% confidence interval (CI) 3.9–6.9 months]. Median survival time after diagnosis of brain metastases was 1.5 months for patients who received only steroids (15.9%), 4.0 months for those who received whole-brain radiation therapy (37.5%), 9.5 months for those who received gamma-knife surgery (GKS) (32.5%), and 11.5 months for those who underwent surgery (20%) (P < 0.001). On multivariate analysis, recursive partitioning analysis (RPA) class and amount of chemotherapy before brain metastasis were independent prognostic factors for survival. Overall prognosis of patients with brain metastases from CRC is poor. Nevertheless, patients with low RPA class, or those with previous less chemotherapy showed good prognosis, indicating that proper treatment may result in improved survival time.     

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.     

Outcome of whole-brain irradiation for breast cancer patients

PURPOSE: To determine the overall survival (OS) of breast cancer patients treated by Whole Brain Radiation Therapy (WBRT) and possible important prognostic factors for OS. MATERIAL AND METHODS: The study population comprised 99 patients with brain metastases (BM) treated with WBRT in the period 1988 to 2004 at St. Olavs University Hospital, Trondheim, Norway. Prognostic factors as age, performance status, axillary lymph node involvement and extent of BM were evaluated. RESULTS: Median survival (range) of the total population from start of irradiation was 5.3 (0.3-157) months. For patients >60 years, 40-60 years and <40 years median survival (range) were 4.5 (0.3-92), 6.8 (0.3-157) and 8.5 (0.8-11) months, respectively (NS, p=0.5), and for Karnofsky performance status (KPS) < or >70, were 3.7 (0.3-92) and 6.8 (1.0-157) months, respectively (NS, p=0.17). One,three, 12 and 24 month survival rate were 90, 64, 29 and 11%, respectively. Grouping patients according to Recursive Partitioning Analyses (RPA) classes, the median survival (range) were 8.0 (1.0-157), 6.5 (1.3-92) and 3.5 (0.3-92) months for RPA class 1, 2 and 3, respectively (NS, p=0.6). CONCLUSION: KPS and in particular the extent of BM were the most important prognostic factors. Grouping patients into RPA classes may be important when deciding whether breast cancer patients should be aggressively treated for their BM.     

Brain metastases from colorectal carcinoma: a description of 60 cases in a single Chinese cancer center

The incidence of brain metastasis (BM) from colorectal carcinoma (CRC) is increasing. The objectives of the present study were to explore the clinical characteristics and potential prognostic factors in CRC patients with BM. Between April 1991 and December 2010, all CRC patients treated in the Sun Yat-sen University Cancer Center were retrospectively reviewed and 60 patients were identified to have BM (36 males and 24 females). The association between patients and their tumor characteristics, treatment modality, and survival were statistically analyzed. The median age at diagnosis of BM was 62.5 years. Fifty-three patients (88.3%) developed extracranial metastases at diagnosis of BM. The cause of death was systemic disease in 19 patients and neurological disease in 23 patients. Brain metastases were primarily treated with either whole brain radiation therapy (WBRT; 15 patients), stereotactic radiosurgery (SRS; nine patients), or surgical resection (seven patients). Ten patients received WBRT and SRS, and 19 patients (31.7%) were treated with steroids alone. The median survival after diagnosis of BM was 8 months (95% confidence interval = 4.2–11.8 months). Recursive partitioning analysis (RPA) class, the number of brain lesions, and treatment modality type were significantly associated with survival. Although BM from CRC is a late-stage phenomenon with an extremely poor prognosis, some subsets of patients would benefit from a multidisciplinary management strategy. A low RPA class and a limited number of brain lesions may predict increased survival after therapy for CRC patients with BM.     

Prognostic factors derived from recursive partition analysis (RPA) of radiation therapy oncology group (RTOG) brain metastases trials applied to surgically resected and irradiated brain metastatic cases

Purpose: (a) To identify the prognostic factors that determine survival after surgical resection and irradiation of tumors metastatic to brain. (b) To determine if the prognostic factors used in the recursive partition analysis (RPA) of brain metastases cases from Radiation Therapy Oncology Group (RTOG) studies into three distinct survival classes is applicable to surgically resected and irradiated patients.Method: The medical records of 125 patients who had surgical resection and radiotherapy for brain metastases from 1985 to 1997 were reviewed. The patients’ disease and treatment related factors were analyzed to identify factors that independently determine survival after diagnosis of brain metastasis. The patients were also grouped into three classes using the RPA-derived prognostic parameters which are: age, performance status, state of the primary disease, and presence or absence of extracranial metastases. Class 1: patients ≤ 65 years of age, Karnofsky performance status (KPS) of ≥70, with controlled primary disease and no extracranial metastases; Class 3: patients with KPS < 70. Patients who do not qualify for Class 1 or 3 are grouped as Class 2. The survival of these patients was determined from the time of diagnosis of brain metastases to the time of death.Results: The median survival of the entire group was 9.5 months. The three classes of patients as grouped had median survivals of 14.8, 9.9, and 6.0 months respectively (p = 0.0002). Age of < 65 years, KPS of ≥ 70, controlled primary disease, absence of extracranial metastases, complete surgical resection of the brain lesion(s) were found to be independent prognostic factors for survival; the total dose of radiation was not.Conclusion: Based on the results of this study, the patients and disease characteristics have significant impact on the survival of patients with brain metastases treated with a combination of surgical resection and radiotherapy. These parameters could be used in selecting patients who would benefit most from such treatment.     

152例肺癌脑转移立体定向放疗预后分析

目的 分析肺癌脑转移的立体定向放疗(SRT)疗效和预后因素。方法 回顾分析行SRT的 152例肺癌脑转移病例。单纯SRT组 59例,SRT加全脑放疗(WBRT)组 40例,WBRT失败后SRT挽救组 53例。Logrank法单因素分析,Cox模型多因素分析。结果 全组随访率为97.4%。单纯SRT组,SRT加WBRT组和SRT挽救组6个月、l年局部控制率分别为96.0%、93.4%,94.2%、90.8%和81.7%、77.5%(χ²=5.39,P=0.068),1、2、5年生存率分别为47.4%、23.7%、8.5%,55.0%、20.0%、0%和41.5%、7.5%、1.9%(χ²=4.08,P=0.130)。单因素分析显示诊断肺癌到脑转移时间、卡氏评分、肺癌切除、GPA分级、RPA分级、颅外病变是影响生存的因素(χ²=11.97、5.91、15.48、14.48、15.86、17.36,P=0.001、0.015、0.000、0.000、0.000、0.000)。多因素分析显示RPA分级、肺癌切除与总生存有关(χ²=21.02、8.18,P=0.000、0.004)。全组患者SRT前和后3个月卡氏评分≤70、80、90的比例分别为48.7%、33.6%、17.8%和27.0%、46.7%、26.3%(t=7.16,P=0.000)。     

Radiosurgery for brain metastases: a score index for predicting prognosis

Purpose: To analyze a prognostic score index for patients with brain metastases submitted to stereotactic radiosurgery (the Score Index for Radiosurgery in Brain Metastases [SIR]).

Methods and Materials: Actuarial survival of 65 brain metastases patients treated with radiosurgery between July 1993 and December 1997 was retrospectively analyzed. Prognostic factors included age, Karnofsky performance status (KPS), extracranial disease status, number of brain lesions, largest brain lesion volume, lesions site, and receiving or not whole brain irradiation. The SIR was obtained through summation of the previously noted first five prognostic factors. Kaplan-Meier actuarial survival curves for all prognostic factors, SIR, and recursive partitioning analysis (RPA) (RTOG prognostic score) were calculated. Survival curves of subsets were compared by log-rank test. Application of the Cox model was utilized to identify any correlation between prognostic factors, prognostic scores, and survival.

Results: Median overall survival from radiosurgery was 6.8 months. Utilizing univariate analysis, extracranial disease status, KPS, number of brain lesions, largest brain lesion volume, RPA, and SIR were significantly correlated with prognosis. Median survival for the RPA classes 1, 2, and 3 was 20.19 months, 7.75 months, and 3.38 months respectively (p = 0.0131). Median survival for patients, grouped under SIR from 1 to 3, 4 to 7, and 8 to 10, was 2.91 months, 7.00 months, and 31.38 months respectively (p = 0.0001). Using the Cox model, extracranial disease status and KPS demonstrated significant correlation with prognosis (p = 0.0001 and 0.0004 respectively). Multivariate analysis also demonstrated significance for SIR and RPA when tested individually (p = 0.0001 and 0.0040 respectively). Applying the Cox Model to both SIR and RPA, only SIR reached independent significance (p = 0.0004).

Conclusions: Systemic disease status, KPS, SIR, and RPA are reliable prognostic factors for patients with brain metastases submitted to radiosurgery. Applying SIR and RPA classifications to our patients’ data, SIR demonstrated better accuracy in predicting prognosis. SIR should be further tested with larger patient accrual and for all patients with brain metastases subjected or not to stereotactic radiosurgery.     

Generation of a New Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer Treated With Whole Brain Radiotherapy (BMS-Score) and Validation of Two Other Indices

Introduction

Patients with small-cell lung cancer (SCLC) demonstrate an exception in the treatment of brain metastases (BM), because in patients with SCLC whole brain radiotherapy (WBRT) only is the preferred treatment modality. The purpose of this study was to develop a prognostic score for patients with brain metastases from SCLC treated with WBRT.

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 free survival differs between breast cancer subtypes

Background:

Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010.

Methods:

Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan–Meier method and compared with the log-rank test.

Results:

Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34–16.66) compared with 18 months (95% CI: 14.46–21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71–44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014).

Conclusion:

Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes.     

Breast cancer subtypes and survival in patients with brain metastases

Introduction

Brain metastases (BM) occur in up to one third of patients with metastatic breast cancer (MBC), whose incidences and prognoses by breast cancer subtypes in BM have not been well delineated.

Methods

Retrospective survival analyses were performed in 126 BM patients from 805 MBC patients treated at the National Cancer Center between August 2001 and April 2006, according to clinical characteristics, breast cancer subtypes, and receipt of trastuzumab. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) statuses were tested by immunohistochemical (IHC) staining, and HER2 FISH analysis conducted for IHC 2+.

Results

The proportion of HER2+/ER- (29% vs 16%) and triple-negative (37% vs 25%) tumors was higher in the 126 BM patients than those without BM. While median survival after recurrence was longer in patients with luminal A disease (median survival of luminal A vs luminal B vs HER2+/ER- vs triple-negative: p = 0.0246; 39.6 vs 27.4 vs 20.9 vs 15.5 months), survival was shorter from BM to death in luminal A and triple negatives (median survival: p = 0.0113; 4.0 vs 9.2 vs 5.0 vs 3.4 months). Receipt of trastuzumab after BM was a significant variable for survival in HER2+ patients. Multivariate analyses identified ER-negative, HER2-negative, or triple-negative, as well as older age, presence of leptomeningeal disease, and three or more extracranial disease sites, as poor prognostic factors for survival after BM.

Conclusion

MBC patients who developed BM had higher proportions of triple-negative and HER2+/ER- tumor status. Triple receptor status is a useful prognostic marker for predicting survival after BM in metastatic breast cancer patients.     

Prognostic Factors and Survival According to Tumor Subtype in Women With Breast Cancer Brain Metastases

Breast cancer (BC) is the second most cause of central nervous system (CNS) metastases. Studies report that almost one third of patients (pts) with triple-negative, one-third with human epidermal growth factor receptor 2 (HER2)-positive and 15% of those with hormone receptor-positive, HER2-negative metastatic breast cancer will develop brain metastases. It is known that the development of symptomatic brain metastases in women with advanced breast cancer is associated with poor prognosis, irrespective of local and systemic treatments. In the present study, we aim to determine the association between BC subtypes and CNS metastases occurrence and prognosis. Retrospective analysis of 309 BC patients with CNS metastases, confirmed by pathological and/or radiological methods, treated in a Cancer Center between 2003 and 2021, was obtained to identify clinicopathologic factors associated with early onset of brain metastases and survival outcomes. For analysis purposes, 3 BC subtypes were considered according to hormone receptor status and HER-2 expression: ER and/or PR positive, HER-2 positive and triple negative. The median time between diagnosis of BC and detection of CNS metastases was 43 months, and it was significantly shorter in triple negative group (8 months). Twenty-one patients (6,8%) had CNS metastases at BC diagnosis, with CNS being the first site of recurrence in 35,3%, mainly in HER2 positive. Most of the patients had parenchymal metastases (n = 245) and 37 (12%) had leptomeningeal (LM) disease, with predominance in ER and/or PR positive subtype (70,3%). In patients submitted to CNS surgery, the concordance between primary tumor and metastases subtype was higher in triple negative (76,9%) compared to 63,2% in HER-2 positive and 38,9% in ER and/or PR positive group (P < 0.05). After CNS involvement, 25,4% (n = 34) of patients with triple negative disease did not receive any systemic therapy, compared to 30,6% (n = 41) in HER-2 positive and 44% (n = 59) in ER and/or PR positive groups (P = 0.05). Median survival after CNS metastases was 9 months, but significantly longer in HER-2 positive group (16 months) and in patients submitted to surgical resection of CNS metastases, irrespectively of subtype (22 months vs 5 months in other treatment modalities). In multivariate Cox regression analysis, having HER-2 positive tumor was an independent prognostic factor for increasing survival after CNS metastases (HR 0.60, 95% CI: 0.41-0.87, P = 0.007), regardless the therapeutic strategy. Clinical behavior and prognosis of CNS metastases varies according to BC subtype. The association between LM disease and ER and/or PR positive tumors should be explored in upcoming studies. Also, these patients’ prognosis depends on the availability of specific treatment options, therefore, innovative and effective therapeutic approaches are needed, in order to improve survival and quality of life of these patients.     

Maximize surgical resection beyond contrast-enhancing boundaries in newly diagnosed glioblastoma multiforme: is it useful and safe? A single institution retrospective experience

The aim of this study was to analyze prognostic factors and evaluate the value of four prognostic scores including RPA, DS-GPA BS-BM, GGS for the EGFR mutant BM patients from lung adenocarcinoma treated with EGFR-TKI. Data of NSCLC were retrospectively reviewed from August 2010 to June 2015 using the medical database of Shanxi Provincial Cancer Hospital. Patients with BM from lung adenocarcinoma with mutant EGFR treated by EGFR-TKI or a combination of EGFR-TKI and WBRT were included. Potential prognostic factors were statistically examined. The C-index of each prognostic score was calculated. A total of 1063 BM patients with lung adenocarcinoma that had been identified with EGFR mutations were reviewed. A total of 104 patients that had been diagnosed with BM were confirmed to have mutant EGFR in primary tumors. These patients received treatment with EGFR-TKI or EGFR-TKI with WBRT to BM. The potential predictive factors in multivariable analysis included KPS (70 vs.70–80 vs. 90–100) and number of brain metastatic lesions. In the log-rank test, the indexes of RPA, DS-GPA BS-BM, and GGS were all significant predictors of OS. The C-indexes of each prognostic score were 0.79, 0.76, 0.77, and 0.74 in DS-GPA, RPA, GGS, and BS-BM, respectively. The indexes of RPA, DS-GPA BS-BM, GGS were applicable for asessing survival stratification in brain metastases from lung adenocarcinoma with presented EGFR mutations in our independent population. The DS-GPA appears to be the best predictive value. However, all four of the indexes could not evaluate the exact independent prognostic factors in multivariable analysis. A prognostic index specific for this group of patients was needed for targeted lung cancer therapy.