基于增强MRI诊断并行全脑放疗的非小细胞肺癌脑转移预后分析

背景与目的肺癌脑转移约占脑转移瘤的20%-40%。本研究旨在探讨基于增强MRI诊断并行全脑放疗的非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移的预后因素。方法回顾性分析2007年4月-2008年10月241例NSCLC脑转移并接受全脑放疗的病例资料,采用Kaplan-Meier法计算生存率,Log-rank法进行单因素分析,Cox回归分析进行多因素分析。结果中位随访时间为19.1个月,全组中位生存时间为8.7个月。影响NSCLC脑转移生存的单因素包括女性、KPS(karnofsky performance score)>70分、脑转移无症状、胸内病变控制、化疗3周期以上及合并靶向治疗。多因素分析显示性别、随访截止时胸内病变控制状态、靶向治疗是影响NSCLC脑转移生存的独立预后因素。结论对于基于增强MRI诊断并行全脑放疗的NSCLC脑转移患者,性别、胸内病变控制、靶向治疗是影响生存的独立预后因素。     

Non–small-cell Lung Cancer With Brain Metastasis at Presentation

Background

Data on the prevalence of brain metastases at presentation in patients with non–small-cell lung cancer (NSCLC) are limited. We queried the National Cancer Data Base to determine prevalence, clinical risk factors, and outcomes of patients with NSCLC presenting with brain metastases.

Factors associated with the development of brain metastases

BACKGROUND

The risk of developing brain metastases after definitive treatment of locally advanced nonsmall cell lung cancer (NSCLC) is approximately 30%‐50%. The risk for patients with early stage disease is less defined. The authors sought to investigate this further and to study potential risk factors.

METHODS

The records of all patients who underwent surgery for T1‐T2 N0‐N1 NSCLC at Duke University between the years 1995 and 2005 were reviewed. The cumulative incidence of brain metastases and distant metastases was estimated by using the Kaplan‐Meier method. A multivariate analysis assessed factors associated with the development of brain metastases.

RESULTS

Of 975 consecutive patients, 85% were stage I, and 15% were stage II. Adjuvant chemotherapy was given to 7%. The 5‐year actuarial risk of developing brain metastases and distant metastases was 10%(95% confidence interval [CI], 8‐13) and 34%(95% CI, 30‐39), respectively. Of patients developing brain metastases, the brain was the sole site of failure in 43%. On multivariate analysis, younger age (hazard ratio [HR], 1.03 per year), larger tumor size (HR, 1.26 per cm), lymphovascular space invasion (HR, 1.87), and hilar lymph node involvement (HR, 1.18) were associated with an increased risk of developing brain metastases.

CONCLUSIONS

In this large series of patients treated surgically for early stage NSCLC, the 5‐year actuarial risk of developing brain metastases was 10%. A better understanding of predictive factors and biological susceptibility is needed to identify the subset of patients with early stage NSCLC who are at particularly high risk. Cancer 2010. © 2010 American Cancer Society.     

非小细胞肺癌微创切除术后骨转移的危险因素

目的:探讨非小细胞肺癌（NSCLC）微创切除术中淋巴结清扫数目与术后骨转移的关系,并分析其危险因素。方法:对医院2013年1月至2018年1月收治的130例实施电视胸腔镜下切除术配合淋巴结清扫术治疗的130例NSCLC患者的临床资料展开回顾,总结术中淋巴结清扫数目,并对比不同淋巴结清扫数目患者术后6个月、1年、2年、3年、4年、5年骨转移率,并利用Logistic多元回归分析明确影响NSCLC患者术后骨转移的危险因素。结果:本组患者中骨转移发生率为40.00%,其中随访6个月、1年、2年、3年、4年、5年者骨转移发生率分别为5.00%、12.12%、40.00%、55.56%、57.89%、69.57%;术中不同淋巴结清扫数目组间术后6个月、1年、2年、3年、4年、5年骨转移发生率对比差异均有统计学意义（P＜0.05）,其中淋巴结清扫＞15且≤30枚者术后不同时刻骨转移发生率均高于≤15枚者和＞30枚者（P＜0.01）;经Logistic回归分析可知,年龄＞60岁、临床III期、术中淋巴结清扫数目＞15且≤30枚、低分化、碱性磷酸酶超标均为NSCLC患者微创切除术配合淋巴结清扫术后骨转移的危险因素（OR=3.182、5.463、3.475、5.978、6.177,P＜0.05）,而系统性淋巴结清扫是其保护因素（OR=0.412,P＜0.05）。结论:NSCLC患者微创切除术中淋巴结清扫数目＞15且≤30枚者术后骨转移风险较高,且年龄＞60岁、临床III期、低分化等均是术后骨转移的危险因素,而系统性淋巴结清扫为其保护因素。     

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.     

White matter lesions reduce number of brain metastases in different cancers: a high-resolution MRI study

Brain metastases are major complications of common cancers. Tumor type and proneness to the CNS are thought to define the number and size of brain metastases. It is not known if intrinsic vascular factors can also have an effect. Restricted perfusion due to cerebral small vessel disease is frequent in elderly patients and causes white matter lesions (WML). The aim of this analysis was to evaluate a possible negative effect of WML and patient age on the number and size of brain metastases (BM) of different tumor entities. Pre-therapeutic 3 T brain magnetic resonance imaging (MRI) of 200 patients with BM were analyzed. Location, size and number of BM (NoM) were determined. T2 hyperintensive WML were scored according to Fazekas-Score (grade I–III). Patients with WML grade 1 (NoM: 5.59; p?=?0.009) and grade 2 (NoM: 3.68; p?=?0.002) had significantly less BM than patients without WML (NoM: 6.99). This effect was present in subgroups of different tumors: NSCLC (p?=?0.05), other tumors than NSCLC (p?=?0.048). Age (≤65 or >65 years) was positively correlated with the degree of WML but not with number (pNoM?=?0.832) or mean diameter (pmDM?=?0.662) of brain metastases. While patient age did not appear to be relevant, increasing WML were associated with lower number of brain metastases in different tumor types.     

Prognostic Factors in Patients with Non-small Cell Lung Carcinoma and Brain Metastases: a Malaysian Perspective

Background: Brain metastases occur in about 20-40% of patients with non-small-cell lung carcinoma(NSCLC), and are usually associated with a poor outcome. Whole brain radiotherapy (WBRT) is widely used butincreasingly, more aggressive local treatments such as surgery or stereotactic radiosurgery (SRS) or stereotacticradiotherapy (SRT) are being employed. In our study we aimed to describe the various factors affecting outcomesin NSCLC patients receiving local therapy for brain metastases. Materials and Methods: The case records of 125patients with NSCLC and brain metastases consecutively treated with radiotherapy at two tertiary centres fromJanuary 2006 to June 2012 were analysed for patient, tumour and treatment-related prognostic factors. Patientsreceiving SRS/SRT were treated using Cyberknife. Variables were examined in univariate and multivariatetesting. Results: Overall median survival was 3.4 months (95%CI: 1.7-5.1). Median survival for patients withmultiple metastases receiving WBRT was 1.5 months, 1-3 metastases receiving WBRT was 3.6 months and 1-3metastases receiving surgery or SRS/SRT was 8.9 months. ECOG score (≤2 vs >2, p=0.001), presence of seizure(yes versus no, p=0.031), treatment modality according to number of brain metastases (1-3 metastases+surgeryor SRS/SRT±WBRT vs 1-3 metastases+WBRT only vs multiple metastases+WBRT only, p=0.007) and the use ofpost-therapy systemic treatment (yes versus no, p=0.001) emerged as significant on univariate analysis. All fourfactors remained statistically significant on multivariate analysis. Conclusions: ECOG ≤2, presence of seizures,oligometastatic disease treated with aggressive local therapy (surgery or SRS/SRT) and the use of post-therapysystemic treatment are favourable prognostic factors in NSCLC patients with brain metastases.     

首发单纯骨转移乳腺癌患者的临床病理特征及预后分析

  目的  探讨乳腺癌首发单纯骨转移（bone-only metastasis, BOM）患者的临床病理学特征及预后特点。  方法  回顾性分析2009年1月至2016年12月967例于天津医科大学肿瘤医院治疗的转移性乳腺癌患者的临床病理资料。分为180例BOM组与787例非BOM组, 对BOM组患者的预后因素行单因素分析和Cox回归模型多因素分析, 并根据激素受体（hormone receptor, HR）状态、转移数目及治疗方式行亚组分析。  结果  BOM组与非BOM组患者的中位无进展生存（progression-free survival, PFS）时间分别为19.4个月与10.0个月, BOM组中位总生存（overall survival, OS）时间为45.6个月。BOM组与非BOM组HR阳性患者分别占81.7%（147/180）与64.7%（509/787）（P < 0.001）。Cox回归模型多因素分析显示HR状态、转移位置、转移数目和治疗方式是BOM患者预后的独立影响因素。BOM组的HR阳性患者内分泌治疗（P=0.004）或联合治疗（P < 0.001）较单独化疗的预后更佳。影响BOM组HR阳性患者预后的主要因素为骨转移数目和内分泌治疗。单部位骨转移患者行内分泌治疗（P=0.004）或联合治疗（P= 0.002）较单独化疗的预后更佳, 多部位骨转移患者行联合治疗较单独化疗（P < 0.001）或内分泌治疗（P=0.04）的预后更佳。  结论  对于HR阳性BOM尤其是单部位骨转移患者, 单纯内分泌治疗可获得较为满意的疗效, 而对于多部位BOM则应考虑行联合治疗。      

Ewing's sarcoma of bone: relation between clinical characteristics and staging

Patients with metastatic Ewing's sarcoma of bone have a poor prognosis. A relation between clinical characteristics and presence of metastatic disease at diagnosis in patients with Ewing's sarcoma of bone was investigated. Data from 618 patients [136 (22%) with metastases at diagnosis] registered at the authors' institution between April 1972 and December 1997 were collected. The distribution of several clinical and hematologic parameters in patients with metastases and those without metastases was analyzed, and clinical risk factors of metastatic disease at presentation were analyzed by means of multivariate logistic regression analysis. All the variables significant at the univariate analysis (age, fever, site, volume, lactic dehydrogenase, anemia, and interval between onset of symptoms and diagnosis) were considered in the multivariate analysis. Pelvic location of the tumor, high level of lactic dehydrogenase, presence of fever, an interval between onset of symptoms and diagnosis less than 3 months, and age older than 12 years were found to be risk factors of clinically evident metastatic disease. In the subset of patients with no risk factors the rate of metastatic disease at presentation was only 4%; in case of contemporary presence of two factors it was 23%, although it was almost double (44%) if three or four factors were present. Only six patients were positive for five factors and all of them had metastases at presentation. The parameters identified are clinical markers of Ewing's sarcoma having a particularly aggressive metastatic behavior.     

Lymph Node Size Predicts for Asymptomatic Brain Metastases in Patients With Non–small-cell Lung Cancer at Diagnosis

Background

We questioned whether the National Comprehensive Cancer Network recommendations for brain magnetic resonance imaging (MRI) for patients with stage ≥ IB non–small-cell lung cancer (NSCLC) was high-yield compared with American College of Clinical Pharmacy and National Institute for Health and Care Excellence guidelines recommending stage III and above NSCLC. We present the prevalence and factors predictive of asymptomatic brain metastases at diagnosis in patients with NSCLC without extracranial metastases.

非小细胞肺癌骨转移的预后因素分析

目的：探讨非小细胞肺癌（ NSCLC）骨转移患者骨相关事件（ SREs）的发生,并分析患者的预后因素。方法回顾性分析我科诊治的118例NSCLC骨转移患者SREs的发生率,并分析各预后相关危险因素,单因素分析应用Kaplan-Meier法,多因素分析应用Cox回归模型。结果118例患者中,44例（37.3%）在初诊为骨转移时即发生SREs,118例患者中位生存时间为13（11.11~14.89）个月,单因素分析显示,病理类型、骨转移灶数目、PS评分、诊断骨转移时是否发生SREs、是否给予靶向治疗与预后有关;而多因素分析则显示病理类型、骨转移灶数目、PS评分、是否给予靶向治疗是影响预后的独立因素。结论在发生SREs的NSCLC骨转移患者中,对腺癌、单发骨转移灶、PS评分为0~1分的患者给予更积极的治疗,有可能使这部分患者生存受益。     

非小细胞肺癌脑转移患者放疗后的生存状况及预后分析

目的：探讨非小细胞肺癌脑转移放疗后生存状况及预后的相关因素。方法：回顾性分析本院2004年9月-2007年12月58例非小细胞肺癌脑转移患者的临床资料,Kaplan Meier法进行生存率统计,并进行Log-rank时序检验,利用比例风险模型（Cox模型）进行多因素分析,筛选相关因素。结果：非小细胞肺癌脑转移患者放疗后的1年生存率为37.9%,2年生存率13.8%。单因素分析结果显示,患者的KPS评分、脑转移数目、有无颅外转移、原发病灶控制情况及放疗方法对生存期有影响（P〈0.05）,多因素分析显示,KPS评分、脑转移灶数目是预后的独立因素（P〈0.05）。结论：患者的KPS评分、脑转移灶数目、原发病灶控制情况、有无颅外转移及放疗方式是非小细胞肺癌脑转移的预后因素。KPS≥70分,脑转移灶为单发是肺癌脑转移患者良好的独立预后因素,这些患者的生存期较长,是潜在的治疗获益者。     

Predictors of distant brain recurrence for patients with newly diagnosed brain metastases treated with stereotactic radiosurgery alone

PURPOSE: To ascertain predictors of distant brain failure (DBF) in patients treated initially with stereotactic radiosurgery alone for newly diagnosed brain metastases. We hypothesize that these factors may be used to group patients according to risk of DBF. METHODS AND MATERIALS: We retrospectively analyzed 100 patients with newly diagnosed brain metastases treated from 2003 to 2005 at our Gamma Knife radiosurgery facility. The primary endpoint was DBF. Potential predictors included number of metastases, tumor volume, histologic characteristics, extracranial disease, and use of temozolomide. RESULTS: One-year actuarial risk of DBF was 61% for all patients. Significant predictors of DBF included more than three metastases (hazard ratio, 3.30; p = 0.004), stable or poorly controlled extracranial disease (hazard ratio, 2.16; p = 0.04), and melanoma histologic characteristics (hazard ratio, 2.14; p = 0.02). These were confirmed in multivariate analysis. Those with three or fewer metastases, no extracranial disease, and nonmelanoma histologic characteristics (N = 18) had a median time to DBF of 89 weeks vs. 33 weeks for all others. One-year actuarial freedom from DBF for this group was 83% vs. 26% for all others. CONCLUSIONS: Independent significant predictors of DBF in our series included number of metastases (more than three), present or uncontrolled extracranial disease, and melanoma histologic characteristics. These factors were combined to identify a lower risk subgroup with significantly longer time to DBF. These patients may be candidates for initial localized treatment, reserving whole-brain radiation therapy for salvage. Patients in the higher risk group may be candidates for initial whole-brain radiation therapy or should be considered for clinical trials.     

Distribution of metastatic sites in renal cell carcinoma: a population-based analysis

BackgroundWe assessed the distribution of site-specific metastases in patients with renal cell carcinoma (RCC) according to age. Moreover, we evaluated recommendations proposed by guidelines and focused specifically on bone and brain metastases.Patients and methodsPatients with metastatic RCC (mRCC) were abstracted from the Nationwide Inpatient Sample (1998–2007). Age was stratified into four groups: <55, 55–64, 65–74 and ≥75 years. Cochran–Armitage trend test and multivariable logistic regression analysis tested the relationship between age and the rate of multiple metastatic sites. Finally, we examined the rates of brain or bone metastases according to the presence of other metastatic sites.ResultsIn 11 157 mRCC patients, the rate of multiple metastatic sites decreased with increasing age (P < 0.001). This phenomenon was confirmed in patients with lung, bone, liver and brain metastases (all P ≤ 0.01). The rate of bone metastases was 10% in patients with exclusive abdominal metastases and 49% in patients with abdominal, thoracic and brain metastases. The rate of brain metastases was 2% in patients with exclusive abdominal metastases and 16% in patients with thoracic and bone metastases.ConclusionsThe proportion of patients with multiple metastatic sites is higher in young patients. The rates of bone (10%–49%) and brain (2%–16%) metastases are nonnegligible in mRCC patients.     

Gamma knife stereotactic radiosurgery for synchronous versus metachronous solitary brain metastases from non-small cell lung cancer

A retrospective study was conducted analyzing the clinical outcome and various prognostic factors in patients treated with gamma knife stereotactic radiosurgery (GK-SRS) for solitary brain metastasis from non-small cell lung carcinoma (NSCLC). A total of 72 patients from June of 1992 to January of 1999 were treated. All patients received GK-SRS to a median dose of 18Gy, with 45 patients receiving additional whole-brain radiation therapy. No one had evidence of extra-cranial metastasis at the time of diagnosis of brain metastases. The median follow-up was 15.7 months for the entire population and 99.5 months for those who were alive at the last follow-up. Univariate and multivariate analyses were used to test the impact of various prognostic factors on survival. The median and 5-year actuarial survivals for the entire cohort were 15.7 months and 10.4%, respectively. The presence of a metachronous versus a synchronous brain metastasis was the only factor significant in the univariate (P=0.045) and multivariate (P=0.002) analyses. Patients with metachronous solitary brain metastases had a significant median survival advantage compared to those with synchronous metastases (33.3 months versus 8.6 months, P=0.001). However, there was no statistically significant difference in median survival from the time of metastasis when treated with GK-SRS in these groups (12.5 months versus 8.4 months, P=0.50). The addition of WBRT did not improve overall survival (12.0 months versus 7.7 months, P=0.73). The 5-year actuarial survival for the metachronous and synchronous groups were 13.2 and 8.1%, respectively. In conclusion, patients presenting with a solitary metachronous brain metastasis from NSCLC achieved longer survivals than those with a synchronous metastasis. The tail in the survival curves demonstrates that a prolonged survival may be attained in patients with solitary metastases from NSCLC. This study adds to the growing body of literature that supports the use of SRS in the management of this patient population.     

甲磺酸奥希替尼治疗EGFR基因突变型非小细胞肺癌脑转移的疗效评价

目的:探讨甲磺酸奥希替尼治疗表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变型非小细胞肺癌(non-small-cell lung cancer,NSCLC)脑转移的临床效果及预后因素.方法:回顾分析2017年5月-2019年12月60 例由蚌埠医学院第一附属医院肿...     

非小细胞肺癌患者发生脑转移风险列线图预测模型的建立

目的:基于非小细胞肺癌(non-small cell lung cancer,NSCLC)患者发生脑转移风险的影响因素分析,建立列线图预测模型。方法:选取2011年06月至2015年06月在本院确诊为NSCLC的患者452例作为研究对象,收集患者的临床资料并进行随访,如果出现脑转移情况或5年随访时间已满,则随访终止,通过单因素和多因素的Cox回归分析得出发生脑转移风险的影响因素,在此基础上根据筛选出的变量建立列线图预测模型。结果:Cox回归最终筛选出的变量为TNM分期、分化程度、病理类型、CA125水平和淋巴结转移数目,建立的列线图预测模型C-index为0.801（95%CI:0.778~0.882）。结论:本研究建立的NSCLC患者发生脑转移风险的列线图预测模型,可以根据多因素分析结果中有意义的变量,较为准确的预测患者的预后情况,临床应用前景较好。     

伴骨转移的非小细胞肺癌化疗同期三维放疗预后分析

目的 探讨非小细胞肺癌(NSCLC)骨转移的胸部原发灶三维放疗在综合治疗中的作用。方法 选取2003-2010年间伴骨转移的95例Ⅳ期NSCLC化疗≥2周期且同期胸部三维放疗的前瞻性研究资料,其中47例单纯骨转移、48例合并其他脏器转移。Kaplan-Meier法计算生存率,Logrank法组间比较及单因素预后分析,Cox模型行多因素预后分析。结果 随访率95%。1、2、3年生存率分别为44%、17%、9%。单因素分析显示原发灶计划靶体积放疗剂量≥63 Gy、原发肿瘤治疗有效和化疗≥4周期者生存延长(P=0.001、0.037、0.009)。单纯骨转移和合并其它转移患者分别进行分析,原发灶计划靶体积放疗剂量≥63 Gy仍是影响其生存的因素(P=0.045、0.012)。单纯骨转移患者原发肿瘤分期T₁+T₂期较T₃+T₄期患者生存延长(P=0.048)。多因素分析显示原发灶计划靶体积放疗剂量≥63 Gy和单纯骨转移能延长总生存(P=0.036、0.035)。结论 NSCLC骨转移胸部原发灶三维放疗技术及剂量在综合治疗中对改善生存具有重要作用。     

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...     

Prevalence of bone pain decreases as lymph node stage increases in nonsmall cell lung cancer patients

According to lung cancer guidelines, positron emission tomography scan is recommended for initial evaluation of bone metastasis. However, guidelines differ in their recommendations for when it should be used. We investigated the appropriate use of bone imaging in nonsmall cell lung cancer (NSCLC) patients.One hundred seventy-seven consecutive NSCLC patients who had distant metastases at presentation and were admitted between January 2012 and April 2016 were retrospectively reviewed. Among patients with bone metastases, we explored bone pain, number of bone metastases, location of bone metastases, and clinical tumor (T) and lymph node (N) classification.Sixty-three patients had bone metastases. There was a trend toward an increase in prevalence of bone metastases as lymph node stage increased. The prevalence of bone pain significantly decreased as N stage increased (p?=?0.017). N0 and N2-3 patients were more likely to have multiple bone metastases (p?=?0.038). Compared with patients who had a single bone metastasis, patients with multiple metastases had a significantly higher probability of having at least 1 bone metastasis located in the thorax or upper abdomen. All N0 patients have at least 1 bone metastasis in the thorax or upper abdomen.Clinical N0 NSCLC patients with bone metastasis are likely to have bone pain and have multiple bone metastases. N2-3 patients are more likely to have bone metastases but less likely to have bone pain. If NSCLC patients do not have bone pain, and CT of the chest and upper abdomen does not reveal any lymph node or bone metastasis, further survey for bone metastases may be omitted; bone imaging should be performed in N2 and N3 patients regardless of symptoms.