【作者】 何健；

【导师】 曾昭冲； 陈统一； 周俭；

【作者基本信息】 复旦大学 ， 肿瘤学， 2008， 硕士

【摘要】 目的研究肝细胞癌(下称肝癌)、前列腺癌、非小细胞肺癌(下称肺癌)、肾细胞癌、胃腺癌、乳腺癌、直肠腺癌骨转移患者的临床特征及其相关的预后因素。方法收集自1997年至2007年共10年间,在本科接受外照射治疗的肝癌骨转移患者共205例。在接受放射治疗之前了解这些患者一般信息、实验室指标、肿瘤特点(原发灶及骨转移灶)以及以往的治疗形式,放疗剂量范围为32～66Gy,中位剂量50Gy,放射区为转移累及骨。对患者的性别、Karnofsky评分、肝功能状况(Child-Pugh分级)、乙肝表面抗原、肝内原发灶的大小、数目、控制情况、骨转移时AFP的水平、r-GT的水平、ALT水平、AST水平、ALP水平、血红蛋白、白细胞计数、血小板计数、总胆红素、白蛋白、白/球比率以及骨转移灶的数目、骨转移时是否伴有骨旁软组织和其他脏器转移、是否行肝移植术等多项因素进行分析。收集本院1997～2007年间诊治的前列腺癌骨转移患者115例、非小细胞肺癌骨转移患者148例、肾细胞癌骨转移患者45例、胃腺癌骨转移患者38例、乳腺癌骨转移患者46例及直肠腺癌骨转移患者32例,收集其临床病史影像学及病理学检查资料、血液指标及治疗方法等。上述病例均随访至2007年12月31日,均进行回顾性分析。用SPSS15.0在Windows XP下进行单因素和多因素分析,生存率用Kaplan-Meier法计算,单因素分析用Log-rank方法,多因素分析采用Cox回归模型。结果肝癌骨转移患者1、2、3年生存率分别为32.4%、13.2%、8.5%,中位生存期7.4个月。205名肝癌骨转移患者的特征是溶骨性破坏为主,伴有成骨成分,有80例(39%)骨转移灶周围伴有软组织肿块者。在照射剂量32～66Gy的患者中,我们并没有发现骨转移症状的减轻与剂量有明显关系,其剂量与效应之间并不呈正相关。不过骨转移灶周围伴有软组织肿块者的患者再治疗率相对比较高。通过单因素分析,我们发现较短的生存率和以下几方面有关:较低的Karnofsky评分、低白蛋白水平、较高的骨转移时ALP、r-GT和AFP水平、肝内肿瘤大于5cm、肝内原发灶未控、多发骨转移灶、累及脊椎、骨外其他脏器转移以及诊断肝癌至出现骨转移的时间较短。在多因素分析中,较低的Karnofsky评分、骨转移时较高的AFP水平、AST水平、血小板计数、肝内原发灶未控制、前5年的治疗诸因素均为独立预后因子(P值均＜0.05),与预后有关。前列腺癌骨转移生存率,1年为89.1%,2年76.9%,3年60.9%,5年49.8%,中位生存期48.5个月。其单因素分析显示患者年龄、原发灶Gleason评分、初诊时临床分期、骨转移灶数目、发生骨转移时ALP水平、是否伴有非区域淋巴结转移、是否伴有其他脏器转移诸因素对预后有影响。其Cox多因素分析显示骨转移灶数目、骨转移时ALP水平、诊断原发灶时Gleason评分、年龄、非区域淋巴结转移诸因素对预后有影响。肺癌骨转移患者生存率,1年为52.2%,2年26.5%,3年21.2%,5年3.7%,中位生存期13个月。其单因素分析显示骨转移灶数目、骨转移时ALP水平、骨转移时是否伴有其他脏器转移诸因素对预后有影响。其Cox多因素分析显示初诊时临床分期、骨转移时ALP水平、是否伴其他脏器转移及骨转移灶数目诸因素对预后有影响。肾癌患者出现骨转移后其生存率明显下降,其骨转移患者生存率,1年为54.0%,2年26.0%,3年17.3%,中位生存期14.0个月,其单因素分析显示骨转移时ALP水平、骨转移时是否伴其他脏器诸因素对预后有影响。其Cox多因素分析显示骨转移时ALP水平、是否伴其他脏器转移、是否伴有淋巴结转移诸因素是影响预后的因子。胃癌骨转移患者生存率,1年为47.1%,2年29.6%,3年24.7%,中位生存期5.5个月。其单因素分析显示骨转移时CEA水平、ALP水平对预后有一定影响。其Cox多因素分析显示骨转移时ALP水平及是否伴有淋巴结转移诸因素对预后有影响。乳腺癌患者出现骨转移后其生存率明显下降,其骨转移患者生存率,1年为87.2%,2年68.3%,3年62.6%,5年46.9%,中位生存期43个月。其单因素分析显示是否伴有其他脏器转移及骨转移时ALP水平对预后有影响。Cox多因素分析显示乳腺癌骨转移患者的原发灶大小、骨转移时ALP水平、原发灶是否化疗、是否伴有淋巴结转移、骨旁软组织转移及其他脏器转移诸因素对预后无影响。直肠癌骨转移以中老年患者居多,出现骨转移后其生存率明显下降。其骨转移患者生存率,1年为49.4%,2年27.5%,3年27.5%,中位生存期12个月。其单因素分析显示骨转移时ALP水平、是否伴其他脏器转移对预后有影响。其Cox多因素分析显示骨转移时ALP水平及原发灶大小二因素是影响预后的独立因子。结论肝癌骨转移患者经外照射后症状明显缓解,但远期疗效仍然很差,对预计生存期短者,可考虑采用大剂量短疗程放射治疗,预计生存期长者,采用常规分割。肝内原发灶控制情况、Karnofsky评分、骨转移时肝功能ALT水平和AST水平、血小板计数诸因素均为独立预后因子。这些预后因素对决定恰当的放射总剂量和单次照射剂量有所帮助。前列腺癌骨转移灶数目、骨转移时ALP水平、诊断原发灶时Glason评分、年龄、非区域淋巴结转移诸因素是影响其预后的因子。其骨转移患者生存期长,远期疗效较好,其放疗的剂量分割方式,一般应以常规分割或30GY/10次为主。肺癌骨转移时伴有一定比例的其他脏器转移,提醒我们在发现骨转移的同时应注意检查其他脏器。初诊时临床分期、骨转移时ALP水平、是否伴其他脏器转移及骨转移灶数目诸因素是影响预后的独立因子。其中位生存期13个月,对预计生存期短者,可考虑采用大剂量短疗程放射治疗,预计生存期长者,采用常规分割。肾癌骨转移时ALP水平、是否伴其他脏器转移及淋巴结转移诸因素是影响预后的独立因子。其中位生存期12个月,对预计生存期短者,用大剂量短疗程放射治疗,预计生存期长者,采用常规分割。胃癌患者出现骨转移后其生存率明显下降,骨转移时ALP水平及是否伴淋巴结转移诸因素是影响预后的因子。其生存期短,一般可考虑采用大剂量短疗程放射治疗或30GY/10次为主。乳腺癌骨转移患者生存期长,远期疗效较好,对此类患者需积极处理其骨转移灶,照射方式应视每个患者具体情况而定,但以常规分割或30GY/10次为主。直肠癌骨转移后其生存率明显下降,骨转移时ALP水平及原发灶大小二因素是影响其预后的独立因子。其中位生存期12个月,对预计生存期短者,用大剂量短疗程放射治疗,预计生存期长者,采用常规分割。更多还原

【Abstract】 Purpose To identify clinical features and independent.predictors for patients with bone metastases from thoracic or abdominal cancers(hepatocellular carcinoma(HCC), prostate cancer,non-small-cell lung cancer(NSCLC),kidney cancer,stomach cancer,breast cancer,rectum cancer).Materials and Methods We retrospectively analysed 205 patients with bone metastases from HCC received external beam radiation therapy(EBRT) from 1997 to 2007 in department of radiation oncology,Fudan University Zhong Shan Hospital. Demographic variables,laboratory values,tumor characteristics(intrahepatic primary tumors and metastatic lesions) before EBRT and the treatments were recorded.Total radiation dose ranged from 32 to 60Gy(median:50Gy) and was focused on the involved bone.Statistical analysis was done using statistical package for social sciences,version 15.The Kaplan-Meier model was used to estimate the survival and control rates.The Cox proportion hazard model was used for multivariate analysis, occording to gender,KPS,liver function(Child-Pugh classification),HBsAg,tumor size and number,controll statuses of the intrahepatic lesions,level of AFP r-GT,ALT, AST,ALP,hemaglobulin,WBC,platelets,total bilirubin,albumin,A/G ratio,number of bone lesions,soft tissue expansion,liver transplantation history.The cohorts involved the patients with bone metastases from prostate cancer (n=115),NSCLC(n=148),kidney caner(n=45),stomach cancer(n=38),breast cancer (n=46),and rectum cancer(n=32).The patients were followed up to Dec 31,2007.Results One-,2-,3-year survival rates and median survival were 32.4%,13.2%, 8.5%and 7.4 months for patients with bone metastases from HCC,respectively.Of 205 patients with HCC,80(39%) was with expansile soft tissue masses,and Osteolytic lesions in most cases was found.Radiation dose was 32 to 66Gy.The relationship between dose and pain relief was not found,but the retreatment rate was higher in patients with expansile soft tissue.On univariate analyses,shorter survival was associated with poored performance status,lower albumin levels,higher alkaline phosphatase,r-glutamyltransferase and a-fetoprotein levels;tumor size＞5 cm, ucontrolled intrahepatic tumors;multifocal bone lesions,involvement of spinal vertebrae,extraosseous metastases,shorter disease-free interval after an initial diagnoses of HCC.On multivariate analysis,pretreatment unfavorable predictors were associated lower performance status;higher platelet count;higher aspartate aminotransferase,r-glutamyltransferase,and a-fetoprotein levels;uncontrolled intrahepatic tumor;and treatments received in the previous 5 years.One-,2-,3-year survival rates and median survival were 89.1%,76.9%,60.9% and 48.5 months for patients with bone metastases from prostate cancer,respectively. On univariate analysis,age,Gleason score,stage,number of bone lesions,ALP level, non-local-regional lymph node metastases,other organ metastases were prognostic factors.On multivariate analysis using cox regression,number of bone lesions,ALP level,Gleason score,age,non-local-regional lymph node metastases were prognostic factors.One-,2-,3-year survival rates and median survival were 52.2%,26.5%,3.7% and 13.0 months for patients with bone metastases from NSCLC,respectively.On univariate analysis,number of bone lesions,ALP level,other organ metastases were prognostic factors.On multivariate analysis using Cox regression method,stage,ALP level,other organ metastases,number of bone lesions were prognostic factors.One-,2-,3-year survival rates and median survival were 54.0%,26.0%,17.3% and 14.0 months for patients with bone metastases from kidney cancer,respectively. On univariate analysis,ALP level,other organ metastases were prognostic factor.On multivariate analysis using Cox regression,ALP level,other organ metastases,lymph node metastases were prognostic factors.One-,2-,3-year survival rates and median survival for patients with bone metastases from stomach cancer were 47.1%,29.6%,24.7%and 5.5 months, respectively.On univariate analysis,CEA level,ALP level were prognostic factors. On multivariate analysis using Cox regression,ALP level,lymph node metastases were prognostic factors.One-,2-,3-year survival rates and median survival for patients with bone metastases from breast cancer were 87.2%,68.3%,62.6%and 43.0 months, respectively.On univariate analysis,other organ metastases,ALP level were prognostic factors.On multivariate analysis using Cox regression,size of primary tumors,ALP level,chemotherapy to primary tumors,lymph node metastases,with or without soft tissue expansion,other organ metastases were all entered with Backward:LR method and not significant prognostic factor was found.One-,2-,3-year survival rates and median survival for patients with bone metastases from rectum cancer were 49.4%,27.5%,27.5%and 12 months, respectively.On univariate analysis,ALT level when bone metastases occurred,other organ metastases were prognostic factors.On multivariate analysis using Cox regression,ALT level when bone metastases occurred,primary tumor size were prognostic factors.Conclusion Patients with bone metastases from HCC received EBRT had significant pain relief,but long term survival is still poor.Controlled intrahepatic tumor,Karnofsky score,ALT and AST level and liver function,platelet count are independent predictors.This study provides detailed information about clinical features,survival outcomes and prognostic factors for HCC with bone metastases in a relatively large cohort of patients treated with EBRT,these prognostic facrtors will help in determining which dose and fraction are appropriate.Patents with bone metastases from prostate cancer received EBRT had significant pain relief,long term survival is high than bone metastasis from other caner,ALP level and gleason score,age,absence of regional lymph node metastases are independent predictors.For patients with bone metastases from prostate cancer,the bone lesions should be treated aggressively to improve patients’ qualities of life.Bone metastases from NSCLC often occompanied by other distant metastases beyond bone.EBRT can relive pain significantly.Stage,ALP level,other organ metastases,number of bone metastases were independent predictors.The survival rate was lower in patients with bone metastases from kidney cancer than those without bone metastases.Patients’ pain had been relief after EBRT.Long term follow up was poor.ALT level,other organ metastases,lymph node metastases when bone metastases occurred are independent prognostic factors.The survival rate was the lowest in patients with bone metastases from stomach cancer comparison to those without bone metastases.ALT level,lymph node metastases when bone metastases occurred were prognostic factors.The survival rate was lower in patients with bone metastases from breast cancer than those without bone metastases.Patients had apparent pain relief after EBRT,long term survival is high.For patients with bone metastases from breast cancer,the bone lesions should be treated aggressively to improve patients’ qualities of life.Patients with bone metastases from rectum cancer were mainly aged persons,the survival rate was low when metastases to bone.ALT level when bone metastases occurred,primary tumor size were prognostic factors.更多还原