非小细胞肺癌脑转移的研究进展

非小细胞肺癌脑转移的治疗对肿瘤学家是一种挑战。虽然近年脑转移研究有所进展,但生存率并不乐观。本文阐述非小细胞肺癌脑转移的临床特点、诊断方法、预后因素以及治疗进展。脑转移最常见的症状为因颅内压力增高所致的头痛。评价脑转移时,头颅MRI较CT优越。最常用的预后标准是肿瘤放射治疗组(RTOG)的RPA分级。关于全脑放疗、立体定向放射外科、手术以及化疗治疗脑转移的作用仍存在争议。全脑放疗常作为脑转移的标准治疗方案。SRS对单一或多个脑转移灶的治疗可代替外科切除。许多数据证明化疗有较好的颅内作用,这引起全身化疗治疗脑转移的研究热点。确立预后因素和其他临床特点后,才能制定最适合个体患者的治疗。     

非小细胞肺癌脑转移手术治疗预后相关因素分析

目的 非小细胞肺癌(non-small cell lung cancer,NSCLC)一旦发生脑转移往往提示预后不良,对于一些脑转移瘤患者,手术仍然是其可选择的治疗方法,但是就如何选择手术获益人群,仍然是神经外科医生面临的难题.本研究就NSCLC脑转移瘤手术切除后组织亚型对患者术后生存期预后影响进行分析.方法 选取2005-01-01-2013-12-31天津医科大学肿瘤医院脑系科收治的78例手术治疗NSCLC脑转移瘤患者的临床病例资料.其中男40例,女38例.年龄38～81岁,中位年龄55岁.以发现脑转移病灶首发44例,发现肺原发病灶首发34例.病灶位于幕上43例,幕下9例,幕上下均累及26例.颅内病灶单发28例,颅内病灶≥2个50例,有颅外其他部位转移26例,仅有颅内部位转移52例,患者术前功能状态评分(karnofsky,KPS)均≥70.结果 患者研究终点是术后生存期,从患者手术之日计算.中位生存期为8.40个月,本研究中只有2例(2.56％)患者其生存期分别为39和52个月,1、2、3年生存率分别为34.5％、11.9％和5.2％.单因素分析显示,性别(x2=5.918,P=0.015)、NSCLC组织亚型(x2=5.361,P=0.021)、脑转移瘤是否首发(x2 =3.932,P=0.047)、脑转移瘤术前化疗与否(x2=4.810,P=0.028)、原发灶控制与否(x2=21.452,P＜0.001)、脑转移术后全脑放疗与否(x2=32.454,P＜0.001)和脑转移术后化疗与否(x2=7.690,P=0.006)对术后生存期有影响.多因素分析显示,NSCLC组织亚型(P=0.001)、原发灶控制与否(P=0.015)、脑转移瘤是否首发(P=0.026)和术后是否行全脑放疗(P＜0.001)是其独立的预后因素.NSCLC中鳞癌脑转移瘤患者中位生存期7.98个月,并且无一例鳞癌脑转移瘤患者生存期＞2年,明显低于NSCLC中腺癌脑转移瘤患者.因此,术后全脑放疗是脑转移瘤患者良好预后因素.结论 在选取手术治疗NSCLC脑转移瘤患者时,考虑由预后等级评估所确定的脑转移个数、KPS评分、年龄以及颅外转移有无等4个参数时,也应该把NSCLC组织亚型对术后预后影响考虑在内.     

Prognostic factors for short-term survival in patients with stage IV non-small cell lung cancer.

Prognostic factors which can forecast short-term survival in patients with stage IV non-small cell lung cancer have not been well evaluated. Characteristics of such factors may be different from those for overall survival, and would be an important eligibility criterion for clinical trials of chemotherapy. We retrospectively analyzed the data of 158 patients with stage IV non-small cell lung cancer whose performance status was 0, 1 or 2. Univariate and multivariate logistic regression models revealed demographic variables which significantly correlated with the survival at 8 or 12 weeks. The univariate model showed the following significant variables: T factor, N factor, number of organs with metastases, grade of performance status, weight loss within 6 months, evidence of metastasis either at bone or lymph node, and lactate dehydrogenase level. The subsequent multivariate model demonstrated that both grade of performance status under 2 and number of metastasized organs less than 3 are important factors for 8- or 12-week survival. The survival rate in patients meeting the two criteria (grade of performance status under 2 and number of metastasized organs less than 3) and in those meeting only one of them was 93% versus 80% at 8 weeks (P = 0.030) and 88% versus 62% at 12 weeks (P < 0.001), respectively. Grade of performance status and number of organs with metastases appear to be important prognostic factors for short-term survival in patients with stage IV non-small cell lung cancer.     

Prognostic factors in non-small cell lung cancer

Identification of prognostic factors is critical in optimizing treatment for patients with cancer. The purpose of this work is to review the modern literature with regard to prognostic factors for patients with non-small-cell lung cancer (NSCLC) taking into account ongoing advances in clinical evaluation, staging, surgery, radiation therapy, chemotherapy, and molecular biology in this widely heterogeneous patient population.     

Prognostic factors in non-small cell lung cancer surgery.

AIMS: Complete surgical resection of primary tumours remains the treatment with the greatest likelihood for survival in early-stage non-small cell lung cancer (NSCLC). Although TNM stage is the most important prognostic parameter in NSCLC, additional parameters are required to explain the large variability in postoperative outcome. The present review aims at providing an overview of the currently known prognostic markers for postoperative outcome. METHODS: We performed an electronic literature search on the MEDLINE database to identify relevant studies describing the risk factors in NSCLC surgery. The references reported in all the identified studies were used for completion of the literature search. RESULTS: Poor pulmonary function, cardiovascular disease, male gender, advanced age, TNM stage, non-squamous cell histology, pneumonectomy, low hospital volume and little experience of the surgeon were identified as risk factors for postoperative outcome. However, with the exception of TNM stage and extent of resection, the literature demonstrates conflicting results on the prognostic power of most factors. The role of molecular biological factors, neoadjuvant treatment and adjuvant treatment is not well investigated yet. CONCLUSIONS: The advantage of knowing about the existence of comorbidity and prognostic risk factors may provide the clinician with the ability to identify poor prognostic patients and establish the most appropriate treatment strategy. The assessment of prognostic factors remains an area of active investigation and a promising field of research in optimising therapy of NSCLC patients.     

非小细胞肺癌预后影响因素分析

目的:探讨非小细胞肺癌(NSCLC)患者的预后相关因素。方法:对2005年6月-2006年6月我院收治的162例非小细胞肺癌患者的临床、病理资料进行回顾性研究,采用Kaplan-Meier和COX回归方法分析评价各因素对预后的影响。结果:单因素分析表明KPS评分、手术与否、临床分期、治疗状况及治疗前血小板(PLT)、癌胚抗原(CEA)和神经元特异性烯醇化酶(NSE)的水平与NSCLC患者的预后有关。多因素分析表明,临床分期、治疗状况、血小板及血清癌胚抗原的水平是独立的预后影响因素。临床分期Ⅳ期、未治疗、PLT>300×109/L、CEA>5.0μg/L时,相对危险度(RR)分别为5.524、16.096、3.563、2.607。结论:治疗前血小板、血清CEA的水平、临床分期及治疗情况是NSCLC患者独立的预后影响因素。     

Psychosocial factors and survival after diagnosis of inoperable non-small cell lung cancer

Objective: Although several previous studies have investigated the association between psychosocial factors and the survival of lung cancer patients, most previous studies were flawed by severe methodological limitations. The purpose of the present study was to use a rigorous study design to investigate the association between relevant psychosocial factors and survival after a diagnosis of inoperable non‐small cell lung cancer (NSCLC). Methods: The subjects were 122 consecutive newly diagnosed patients with inoperable NSCLC. Patients coping with cancer, psychological distress, clinical depression, and social support were evaluated after diagnosis but before treatment and 2 months later. After a 2‐year follow‐up period, 108 patients had died. The survival data were censored for the remaining 14 patients. The influence of psychosocial factors after diagnosis but before treatment on survival time was analyzed using a Cox regression, with adjustments for well‐established (definite and/or possible) prognostic factors. The stability of the investigated psychosocial factors was also examined. Results: None of the examined psychosocial factors significantly predicted survival time among the patients with inoperable NSCLC. Among the biomedical factors that were examined, advanced clinical stage, a high serum lactate dehydrogenase level, and not receiving chemotherapy were independently associated with shorter survival periods. Most of the psychosocial factors exhibited a moderate to high stability. Conclusions: We found little convincing evidence that psychosocial factors after cancer diagnosis had a clinically relevant effect on the survival of inoperable patients with NSCLC. Copyright © 2008 John Wiley & Sons, Ltd.     

早期非小细胞肺癌预后相关因素分析

早期非小细胞肺癌患者首选手术治疗后，仍有部分出现了局部复发和／或远处转移。筛选出预后差的患者辅以综合治疗显得尤为重要。本文分析了近年来研究的一些早期非小细胞肺癌的预后因素。     

Prognostic factors for the survival of surgically treated patients for non-small cell lung cancer

The survival and outcome rates of 284 patients who underwent surgical treatment for non-small cell lung cancer were assessed retrospectively. Resectability rate was 94.1%, hospital mortality 3.9% (n=11) and the mortality rates in patients who underwent pneumonectomy or lobectomy were 8.9% and 0.6%, respectively. The overall 5-year survival was 43.6%. Female gender, earlier stages of disease and a complete resection were strongly predictive for a long-term survival. Women in stage IA disease had a 5-year survival rate of 92.7%. The 5-year survival rate for patients in stages IIIA and N2 disease who underwent a complete resection was 21.9%, and 9% for those who did not undergo a complete resection. It is concluded that the best surgical results were observed in women who were operated on at an early stage of disease. A complete resection also contributed to a better outcome, even for patients in stage IIIA and N2 disease.     

Ⅰ期非小细胞肺癌的预后因素

Ⅰ期非小细胞肺癌(NSCLC)临床预后因素包括肿瘤大小和患者年龄、手术方式和胸膜浸润情况等.分子生物学预后因素包括肿瘤细胞信号通路中的表皮生长因子及其受体、细胞周期素和凋亡基因Bcl-2、p53的异常表达等,以及肿瘤血管生成中基质金属蛋白酶(MMP)、血管内皮生长因子(VEGF)的异常表达等.因此,需要将Ⅰ期NSCLC临床和分子生物学预后因素两方面综合考虑,才能准确判断预后.     

Prognostic factors in patients with stage IV non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths among both men and women over the world. In 2002, lung can- cer accounted for more deaths than breast cancer, prostate cancer, and colon cancer combined[1]. Non-small cell lung cancer (NSCLC) represents 75%–85% of all lung cancers. Lung cancer is hard to discovered until it’s at an advanced stage and the outlook for recovery is poor. Approximately two-thirds of NSCLC patients have advanced-stage at di- agnosis. Stage IV NSCLC denotes …     

Prognostic factors for patients in postoperative brain metastases from surgically resected non-small cell lung cancer

Background

Postoperative recurrence in non-small cell lung cancer (NSCLC) reduces the life expectancy of patients. In this retrospective study, we investigated the prognostic factors in patients with postoperative brain metastases from surgical resected non-small cell lung cancer (NSCLC).

Methods

We conducted a retrospective chart review of patients who had undergone resection for NSCLC between April 2004 and February 2009 and found 65 had experienced postoperative brain metastases by March 2010. We reviewed these patients for clinicopathological information, treatments and responses to treatment, and overall survival.

Results

The 5-year survival rate after the diagnosis of brain metastases was 15.4 %. Significantly favorable prognostic factors for patients after a diagnosis of brain metastases included female gender, adenocarcinoma, a small number (1–3) of brain metastases, no extracranial metastasis at the diagnosis of brain metastases, radiation treatment (whole-brain radiation and/or stereotactic irradiation), and local treatment [stereotactic irradiation and/or surgical operation (craniotomy)]. Furthermore, in patients with only brain metastases as the postoperative initial recurrence, the favorable positive prognostic factors included a small number (1–3) of brain metastases, adjuvant chemotherapy, chemotherapy (including adjuvant and other chemotherapy and excluding epidermal growth factor receptor–tyrosine kinase inhibitors), and local treatment.

Conclusions

Our study found that the foregoing clinical characteristics in postoperative brain metastases and the administration of treatment contributed to patient life expectancy.     

Ⅳ期非小细胞肺癌预后影响因素分析

Objective: To investigate the prognostic factors for stage Ⅳ non-small cell lung cancer (NSCLC) with distant metastasis and establish a reliable model of clinical prognostic index.Methods: From January 1990 to April 2005,313 primary NSCLC patients with metastasis,who had been treated in Shanghai Chest Hospital,were reviewed.Survival time was estimated according to the Kaplan-Meier method.Cox proportional hazard regression model was used for multivariate analysis.Results: Among the 313 cases of non-small cell lung cancer (NSCLC) at stage Ⅳ,there were 218 and 95 patients with metastasis to single and different organs,respectively.The overall median survival time for all 313 cases of NSCLC patients was 10.8 (9.00,12.30)months and the overall 1-,2-,3-,4- and 5-year survival rate was 45%,18%,12%,4% and 0%.There were 63,174,127,36,18,11 and 5 patients with metastasis to brain (20.13%),bone (55.59%),lung (40.58%),liver (11.50%),adrenal gland (5.75%),subcutaneous (3.51%) and others,respectively.The survival time was shortest in subcutaneous metastasis (4.6 months),and liver 7.0 months,brain 8.0 months,adrenal gland 8.6 months,bone 10.6 months,lung 11.8 months.Kaplan-Meier estimation showed that patients anatomic typing,KPS,numbers of organ with metastasis,appetite,liver,adrenal gland and subcutaneous metastasis,body weight loss,smoking,index of smoking,chemotherapy,cycles of chemotherapy were the predictors of survival.Multivariate analysis showed survival statistically significant correlation with anatomic typing,KPS,appetite,liver and subcutaneous metastasis,body weight loss,cycles of chemotherapy.The relative risk (RR) was 1.51,1.97,1.55,1.67,2.56,and 2.56 respectively.Conclusion: Survival time decreases distinctly in patients who had distant metastasis to more than two different organs (P＜0.01).Bone is the commonest organ for distant metastasis in lung cancer.The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis.Independent prognostic factors in patient with stage Ⅳ non-small cell lung cancer were liver and subcutaneous metastasis,anatomic typing,KPS,appetite,body weight loss,cycles of chemotherapy.     

Molecular profiling of non-small cell lung cancer and correlation with disease-free survival

Recent studies have suggested that information from gene expression profiles could be used to develop molecular classifications of cancer. We hypothesized that expression levels of specific genes in operative specimens could be correlated to recurrence risk in non-small cell lung cancer (NSCLC). We performed expression profiling using 19.2 K cDNA microarrays on tumor specimens from a total of 39 NSCLC patients with known clinical follow-up information. Statistical analysis and clustering approaches were used to determine patterns of gene expression segregating with clinical outcome. The results provide evidence that molecular subtyping of NSCLC can identify distinct profiles of gene expression correlating with disease-free survival.     

Osteogenic and brain metastases after non-small cell lung cancer resection

International Journal of Clinical Oncology - A significant number of non-small cell lung cancer (NSCLC) patients develop osteogenic metastases (OMs) and/or brain metastases (BMs) after surgery,...     

Postoperative long-term survival of non-small cell lung cancer patients with skip-N2 metastases

ObjectiveRadical lymphadenectomy is crucial in operations for non-small cell lung cancer (NSCLC). Usually pN1 and pN2 lymph nodes are affected consecutively (N1N2). Nevertheless, pN2 metastases may also occur in the absence of pN1 as skip-N2 metastases (N0N2). Here we compare the long-term survival of N1N2- and N0N2 patients.Materials and methods464 patients underwent surgery for NSCLC at our institution between 2012 and 2017. We retrospectively reviewed data of pN2 stage patients (n = 68). Patients with N1N2 (n = 39) were compared to N0N2 (n = 29) patients. 1-, 3-and 5-year survival rates were measured. Survival was assessed by Kaplan-Meier curves and the cox proportional hazards model was used to identify prognostic factors for overall survival. All patients received adjuvant chemoradiation therapy according to European guidelines.ResultsThe baseline characteristics did not differ between groups. We observed no differences in the histology, localization, or gender in our cohort. N0N2 patients showed significantly better 1- (N1N2: 82.4% vs. N0N2 100%; p = 0.001), 3- (14.7% vs. 63.6%; p=<0.001) and 5-year (9.4% vs. 43.8%; p = 0.001) survival rates. Tumor size (Hazard ratio (HR) 1.46, Confidence interval (CI 95%) 1.03–2.04; p = 0.03) and the occurrence of N1N2 (HR 4.26, CI 2.04–8.91; p < 0.0001) were independent prognostic factors for worse long-term survival. The Kaplan-Meier curves showed a reduced overall survival for N1N2 patients (log-rank N1N2, N0N2 p < 0.0001).ConclusionN1N2 patients have a significantly worse prognosis compared to N0N2 patients. This will aid to classify the heterogeneous pN2-NSCLC patient population more precisely. Further, multimodal therapy should be considered for N1N2 patients.     

Ⅲ期Ⅳ期非小细胞肺癌预后影响因素分析

目的　研究Ⅲ、Ⅳ期非小细胞肺癌 (NSCLC)患者的预后相关因素 ,建立具有临床实用性的预后模型。方法　采用Kaplan Meier和Cox回归方法分析 114例NSCLC患者治疗前血清神经元特异性烯醇化酶 (NSE)、癌胚抗原 (CEA)、Cyfra2 1 1、CA12 5、IL 2、sIL 2R等 6种肿瘤标记物的水平及常规临床因素 ,如年龄、性别、吸烟指数、KPS评分、临床分期等与生存率的关系。结果　单因素分析表明 ,临床分期、KPS评分、性别以及治疗前血清Cyfra2 1 1和CA12 5水平与NSCLC患者生存率有关。多因素分析表明 ,Cyfra2 1 1、临床分期及治疗情况是独立的预后影响因素 ,Cyfra2 1 1>3.5mg/L、临床分期为Ⅳ期、治疗少于 3周期时 ,相对危险性 (RR)分别为 1.6 91,2 .2 2 9和 3.0 35。化疗 3周期及以上的患者 ,Cyfra2 1 1、sIL 2R及临床分期是独立的预后影响因素。建立患者治疗前的预后指数 (PI)模型 :PI =Cyfra2 1 1 sIL 2R Stage。化疗 3周期及以上者 ,PI=0时 ,中位生存期 18个月 ;PI=1或 2时为 8个月 ,PI =3时为 5个月。结论　治疗前血清Cyfra2 1 1、sIL 2R和临床分期 ,是Ⅲ、Ⅳ期NSCLC患者独立的预后影响因素。采用患者治疗前血清Cyfra2 1 1、sIL 2R及临床分期建立的预后指数模型有实际应用价值。     

肺癌神经内分泌分化与术后生存关系探讨

目的 探讨非小细胞肺癌神经内分泌(NSCLC—NE)分化与患者手术后生存关系。方法 收集1997年4月至1999年4月98例肺癌手术切除病理标本，采用免疫组化标记特异性烯醇化酶(NSE)及突触素(SY)，并按强弱区分为“ 、 、 ”。对同一手术病例标本采用电镜观察特异性NE颗粒。术后病例随访36月，最长60月。采用Cox多因素风险模型分析NSCLC-NE分化与患者术后生存的关系。结果 91例为非小细胞肺癌。非小细胞肺癌NF阳性表达率为63．7％(58/91)，其中NSE阳性表达54例(59．3％)，SY阳性表达22例(24．1％)，电镜观察NE持异性颗粒30例(33．0%)。结合免疫组化和电镜观察，NSCLC-NE分化44例(48．4％)。Cox模型多因素分析结果表明NSCLC-NE分化者术后生存时间明显缩短(P=0.048)。术后生存与肺癌细胞分化程度(P=0．006)、病理分期(P=0．001)、NE表达强弱(P=0．054)有密切关系。结论 NSCLC-NE分化与肿瘤细胞分化和患者术后生存有关。采用NE标志物标记肿瘤，并观察其强弱改变．对术后评估具有较重要的参考意义，可作为为临床判断患者预后指标之一。