Objective: To explore the prognosis of patients with leptomeningeal metastasis (LM) and epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC) treated with different kinds of tyrosine kinase inhibitors (TKIs). Methods: From January 2016 to June 2021, the clinicopathological data of 70 patients confirmed by histologically or cytologically EGFRm LM who received different types of TKIs in Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. According to treatment patterns, patients were divided into the first-and second-generation EGFR-TKIs treatment group and the third-generation EGFR-TKIs treatment group [Osimertinib 80 mg once a day], and the prognosis and prognostic factors (with Cox proportional hazards model) of patients in different treatment group were assessed. The next-generation sequencing (NGS) of paired samples of cerebrospinal fluid (CSF) and plasma from 64 patients at the time of LM diagnosis was performed simultaneously. Results: There were 20 males and 50 females in 70 EGFRm NSCLC patients with LM. The age ranged from 35 to 69 years, with a median age of 56 years. A total of 24 patients received the first-and second-generation EGFR-TKIs treatment, and 46 received the third-generation EGFR-TKIs treatment. Twenty-four patients developed disease progression on the first-and second EGFR-TKIs treatments, followed by treatment with the third-generation EGFR-TKIs (Osimertinib) in 12 cases, chemotherapy or anti-angiogenesis therapy in 4 cases, and the optimal supportive treatment in 8 cases. Among the 70 patients, 18 had partial response (PR), 48 had stable disease (SD), and 4 had progressive disease (PD). The objective response rate (ORR) and disease control rate (DCR) were 26% (18/70) and 94% (66/70), respectively. The median follow-up time was 16.5 months. The median progression-free survival (PFS) was 5.3 months(95%CI: 2.8-7.8)in the first-and second-generation EGFR-TKIs and 10.8 months (95%CI: 7.9-13.6) in the third-generation EGFR-TKIs, and the difference was statistically significant (P=0.019). The median overall survival (OS) was 14.9 months (95%CI: 9.7-20.0) and 15.7 months (95%CI: 13.3-18.1) in the two groups, respectively, but no statistical differences was observed (P=0.713). Univariate analysis showed that the PFS of patients with EGFRm LM were related to gender and different types of EGFR-TKIs (P˂0.05). Multivariate analysis demonstrated that male (HR=2.30, 95%CI: 1.31-4.03, P=0.004) and the first-and second-generation EGFR-TKIs (HR=2.03, 95%CI: 1.20-3.41, P=0.008) were independent risk factors for PFS in patients with EGFRm LM. The EGFR mutation was detected in 61 (95%) CSF and in 27 (42%) plasma samples. Conclusion: In EGFRm NSCLC patients with LM, the dose of Osimertinib 80 mg (once a day) has a significant PFS benefit compared with the first-and second-generation EGFR-TKIs.

免疫检查点抑制剂(immune checkpoint inhibitor,ICI)近年来在晚期恶性肿瘤的治疗中具有越来越重要的作用.ICI治疗在获得令人振奋疗效的同时,也可能会诱发多个系统的免疫反应,引起相应的不良反应.虽然心血管系统不良反应发生率低,但其一旦发生,往往进展迅速,致死率高.2017年欧洲肿瘤内科学会(European Society of Medical Oncology,ESMO)发表了《免疫治疗的毒性管理:ESMO诊断、治疗和随访临床实践指南》.2018年美国临床肿瘤学会(American Society of Clinical Oncology,ASCO)联合美国国家综合癌症网络(National Comprehensive Cancer Network,NCCN)发表了《免疫检查点抑制剂治疗相关毒性的管理指南》,NCCN后续对其进行了更新.本文将对上述指南中ICI相关心血管毒性的重要内容进行解读.

Objective To summarize the diagnosis and treatment of refractory brain metastases and leptomeningeal metastases from small cell lung cancer (SCLC). Methods and Results An extensive stage SCLC male patient (44⁃year⁃old) with diffuse parenchymal meningeal metastases and large volume brain metastasis was treated with muti⁃disciplinary team (MDT), namely precise helical tomotherapy with concurrent temozolomide chemotherapy, combined with intrathecal chemotherapy and systemic therapy. After intracranial recurrent, intrathecal chemotherapy and radiotherapy were used to release the symptoms. At last, this patient died of extracranial disease and the survival time after the diagnosis of brain metastases was 16 months. Conclusions For treatment of brain or leptomeningeal metastases, comprehensive and individualized treatment are needed, and MDT treatment discussion is highly recommended. DOI：10.3969/j.issn.1672⁃6731.2019.11.011

[Purpose] To evaluate the application of modified early warning score (MEWS) and simplified acute physiology score Ⅱ (SAPS Ⅱ) in predicting short-term mortality of emergent patients with malignant tumor. [Methods] Clinical data of 200 emergency patients admitted to General Department of National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 2015 to December 2016 were retrospectively reviewed. The patients died with 14 days after admission were classified as fatal group(n=100) and those survived in 14 days after admission were classified as survival group (n=100). The receiver operator characteristic curve (ROC) and the areas under the curve(AUC) were applied to analyze the value of MEWS and SAPS Ⅱ in predicting short-term mortality of patients. Youden index were calculated to get the best cut off values. [Results] KPS in the fatal group was significantly lower than that in the survival group. MEWS and SAPS Ⅱ in the fatal group were significantly higher than those in the survival group. The 3 scores were all of value in predicting short-term mortality of emergency patients with malignant tumor(P=0. 00). AUC of SAPS Ⅱ (0. 874) was larger than that of KPS and MEWS(0. 737 and 0. 742). [Conclusion] SAPS Ⅱ can better predict short-term mortality of emergency patients with malignant tumor than MEWS and KPS, but MEWS and KPS are more convenient and easy to be used.

目的 探讨实体瘤患者发生血流感染(BSI)的病原学特点及导致患者死亡的影响因素,为合理使用抗菌药物提供临床依据.方法 选择2012年1月-2014年12月医院220例实体瘤并发BSI的患者为研究对象,分析患者病原学特点,统计患者的年龄、性别、住院天数、基础疾病等基本信息,采用单因素变量和多因素Logistic回归方法评估影响14-d病死率及住院病死率的影响因素.结果 220例患者共检出病原菌234株,其中革兰阴性菌102株占43.6％,革兰阳性菌100株占42.7％,真菌9株占3.9％,复数菌23株占9.8％;革兰阴性菌住院病死率高于革兰阳性球菌及真菌(P=0.014);多因素Logistic分析结果显示,实体瘤患者发生BSI 14-d病死率与GCS≤8分及血小板≤50 g/L有关,住院病死率与脓毒性休克、Child-C级、GCS≤8分有关(P＜0.05).结论 实体瘤患者BSI的病死率较高,早期识别、有效地逆转器官功能衰竭是降低实体瘤患者BSI病死率有效的方法.

Objective:To observe and assess effect by morphine injection on relieving cancer pain in malignant tumor patients. Methods:A total of 174 patients with cancer pain at general department ward in Tumor Hospital of Chinese Academy of Medical Sciences,who received morphine injection,from March 22nd 2013 to March 26th 2015 were taken for observation and summary of medical data and curative effect by morphine injection. Results:There were 165 cases with single primary cancer and 9 cases with double primary cancer. Numeric rating scale(NRS)score of patients at admission was(5. 04 ± 2. 04)points,along with breakthrough pain by(1. 10 ± 1. 14)times/ day. There were 55 death cases during hospitalization,and the 119 discharged cases had NRS score as(1. 94 ± 1. 27)points and breakthrough pain by(0. 40 ± 0. 83)times/ day. Differences of NRS score and breakthrough pain times in patients be-tween admission and discharge had statistical significance(P < 0. 05). Before administration of morphine injection,the patients had NRS score as(7. 23 ± 1. 78)points. Their score was(1. 43 ± 0. 82)points after 30 min of morphine in-jection application. Their difference had statistical significance(P < 0. 05). Conclusion:Morphine injection can re-markably relieve cancer pain in patients,and improve quality of life.

Objective: To summarize and analyze the clinical data and treatment of the cancer pain clinical pathway. Methods: There were 357 cases in cancer pain clinical pathway, from March 22, 2013 to March 26, 2015, were involved. Their cancer pain numerical rating scale (NRS), breakthrough pain (BTP) and treatment are summarized and analyzed. Results: On admission there are 135 cases (37.8%) with mild pain, 155 cases (43.4%) with moderate pain, 67 cases (18.8%) with severe pain. 172 cases (48.2%) have BTP, of whom 21 have BTP 3 times/day or more. At discharge 68 patients are dead. In the other 289 patients there are 273 cases (76.5%) with mild pain, 15 cases (4.2%) with moderate pain, 1 case (0.3%) with severe pain. 39 cases (10.9%) have BTP, of whom 4 have BTP 3 times/day or more. Conclusions: The intensity and BTP of the patients'cancer pain are significantly decreased under the management of cancer pain clinical pathway.

OBJECTIVE To explore the characteristics of bloodstream infections in patients with malignant tumors and analyze the risk factors so as to provide guidance for reasonable prevention and treatment of the bloodstream infections .METHODS A total of 150 malignant tumor patients who were positive for blood culture from Mar 2013 to Mar 2015 were recruited as the study objects ,then the univariate analysis and multivariate logistic regression a-nalysis were carried out ,and the statistical analysis of data was performed with the use of SPSS 16 .0 software . RESULTS Of 150 patients whose blood specimens were cultured positive for pathogens ,83 (52 .2% ) were positive for gram-negative bacteria ,55 (42 .8% ) were positive for gram-positive bacteria ,and 8 (5 .0% ) were positive for fungi.The Escherichiacoli,Staphylococcus epidermidis,and Klebsiella pneumoniae were the common species of pathogens .The univariate analysis indicated that the risk factors for the bloodstream infections included the neu-tropenia ,mechanical ventilation ,central venous catheter indwelling ,Charlson complication index ,and time of use of antibiotics no less than 7 days (P<0 .05);the multivariate logistic analysis showed that the intravenous cathe-ter indwelling and time of use of antibiotics no less than 7 days were the independent risk factors for the blood-stream infections .CONCLUSION It is an effective way to reduce the invasive operations and strictly control the time of use of antibiotics so as to reduce the incidence of the bloodstream infections .

Objective To analyze the clinical characteristics and prognosis of advanced non-small cell lung cancer(NSCLC) in elderly patients(≥70 years).Methods A retrospective study of the clinical characteristics in 184 cases of advanced NSCLC in elderly patients was described.All the patients were hospitalized between January 2005 and December 2006.All the potential prognostic factors,including gender,smoking status,pathological type,clinical stage,Karnofsky performance score(KPS),simplified comorbidity score(SCS) and therapeutic method were evaluated.Results The median age of study participants was 73 years old,and The 5-year survival rate was 11.4%.Univariate analysis revealed that clinical stage,KPS,SCS and therapeutic method were factors significantly related to prognosis in elderly NSCLC.In multivariate analysis,clinical stages,SCS and therapeutic method may be independent prognostic factors of NSCLC in elderly patients.Conclusions Clinical stages,SCS and therapeutic method may be independent factors prognostic of NSCLC in the elderly.The SCS,appears more informative than the CCI in predicting NSCLC patient outcome.Comorbidities might be taken into account as an important variable on treatment of NSCLC.

目的 探讨影响70岁以上老年非小细胞肺癌( NSCLC)患者预后生存的因素.方法 回顾性分析2005年1月至2006年12月收治的361例70岁以上老年NSCLC患者的临床资料,随访生存情况,分析年龄、性别、吸烟状况、Karnofsky评分(KPS)、TNM分期、病理类型、治疗方式、合并症情况(Charlson合并症指数CCI)等因素,对老年非小细胞肺癌患者生存期的影响.结果 全组患者平均年龄(73.4±3.1)岁(70 ～86岁),确诊肺癌后中位生存期34.0个月(0.3 ～83.0个月),5年生存率34.1％.对年龄、性别、病理类型、是否吸烟、KPS、TNM分期、治疗方式、是否伴有合并症等预后因素进行单因素分析,结果显示:TNM分期、治疗方式、KPS、是否伴有合并症与预后相关.Cox多因素分析显示TNM分期、有无合并症、治疗方式是影响患者生存及预后的独立因素.结论 TNM分期、治疗方式、合并症等多种因素影响70岁以上老年NSCLC患者的预后生存.老年肺癌患者多伴有合并症,重视并积极控制合并症,有助于改善预后,延长生存.

OBJECTIVE To assess the value of an infusion-based separation technique to assist in ultrasound (US)-guided percutaneous radiofrequency ablation (RFA) of liver cancers abutting the liver edge. METHODS Twenty-four cases of malignant liver tumors abutting the hepatic edge were treated with US-guided puncture accompanied by the assistant infusion technique. The US-guided puncture was made with a 22-G needle through the hepatic tissue and into the abdominal cavity near the target tumor. Infusion of a saline solution was used to separate the liver from any surrounding structures so that percutaneous RFA could be safely performed. Complications, including gastrointestinal injury, hemorrhage and death, were recorded. Technical efficacy and safety were evaluated. RESULTS Among the 24 patients, the target tumors were adjacent to the right kidney (n=6), colon (n=6), stomach (n=5), pericardium (n=4), and gall bladder (n=3). Twenty-three patients received a successful radical percutaneous RFA with assistant infusion. The assistant infusion volumes ranged from 80-390 ml and created spaces ranging from 0.8-2.5 cm between the liver and surrounding structures. Five of the cases with tumors adjacent to the stomach or colon received the largest volume infusions. The infusion failed to create a separation space in only one case, due to the presence of an adhesion; as a result, this patient was treated with palliative RFA. The mean hospital stay for all 24 patients was four days after surgery. No severe complications or deaths occurred. At 1-month follow-up, computed tomography images showed that 22 cases had complete ablation, yielding a technical success rate of 95.7% (22/23). No needle track implantation was observed. CONCLUSION Assistant infusion for percutaneous radiofrequency ablation creates a protective space between the liver and surrounding structures in patients with liver tumors abutting the liver edge. This safe and effective assistant technique broadens the range of patients available for percutaneous RFA treatment.

OBJECTIVE:To assess the value of application of percutaneous radiofrequency ablation (RFA) with artificial hydrothorax for liver cancer in the hepatic dome.METHODS:Thirty-two patients with 43 lesions of hepatic malignant tumors in the hepatic dome underwent ultrasound-guided percutaneous radiofrequency ablation (RFA) with artificial hydrothorax. Artificial hydrothorax was created by infusion of saline via an intrathoracically placed 14-G central venous catheter, which was ultrasound-guided percutaneously inserted before RFA, separating the right lung from the hepatic dome. The adverse reaction and therapeutic efficacy were also analyzed.RESULTS:In the 32 patients with 43 lesions in the hepatic dome (4 tumors in segment IV 21 tumors in segment VII and 18 tumors in segment VIII), 18 lesions of 14 patients were not observed by ultrasound before the operation. Thirty-two patients received the ultrasound-guided placement of intrathoracical catheter, and (1606.3 ± 485.9) ml (1000 - 2500 ml) saline solution was infused successfully. After obtaining an image of the whole tumor, 31 patients received percutaneous RFA therapy on schedule, and 22 patients received percutaneous transdiaphragmatic RFA therapy. One patient with 2 lesions gave up the treatment, because one of his tumors was not detectable by ultrasound. Diaphragmatic muscle hemorrhage was seen in two patients, subcutaneous edema in two patients, and pneumothorax in one patient. All the complications were cured, and no serious complications or related death occurred. 1-month follow-up with contrast-enhanced CT/MRI images showed that 29 patients had complete ablation, and the effective rate of this technique was 93.5% (29/31).CONCLUSIONS:Artificial hydrothorax helps us not only to visualize the whole tumor in the hepatic dome, but also offers a transdiaphragmatic route for therapy. Ultrasound-guided percutaneous RFA with artificial hydrothorax is a feasible, safe, and effective technique for treating liver cancer in the hepatic dome and worthy of being promoted.

Objective This study aimed at validating the Charlson comorbidity index(CCI) and Simplified comorbidity score(SCS) in elderly patients with Non-small cell lung cancer(NSCLC),and assess the impact of comorbidity on prognosis and survival.Methods We retrospectively reviewed 693 patients with NSCLC who were hospitalized in The Cancer Hospital of Chinese Academy of Medical Sciences between January 2005 and December 2006.All the potential prognostic factors,including gender,age,smoking status,pathological type,clinical stage,Karnofsky performance score(KPS),CCI,SCS and therapeutic method were evaluated.Univariate analysis by Kaplan-Mierer combining with log-rank test and multivariate Cox regression model was used to determine the significance of prognostic variables in the survival.Results Of all the patients,the median survival was 34.0 months(0.2-84.0 months) and the five-year survival rate was 35.4%.Univariate analysis revealed that smoking status,clinical stage,KPS,SCS and therapeutic method were factors significantly related to prognosis and survival in elderly NSCLC.Multivariable analysis showed that clinical stages,SCS,therapeutic method were independent prognostic factors.Conclusions Clinical stages,SCS,therapeutic method may be independent prognostic factors of NSCLC in the elderly.The SCS appears more informative than the CCI in predicting NSCLC patient outcome.Comorbidities might be taken into account as an important variable on treatment of NSCLC.

Objective:To observe the effect and security of continued pericardial drainage and pericardial infusion in treatment of malignant pericardial effusion.Methods:38 malignant pericardial effusion patients all accepted systemic chemotherapy and continued pericardial drainage,in which 15 patients were infused IL-2 into their pericardial cavities(IL-2 Group),13 patients were infused chemotherapy into their pericardial cavities(Chemotherapy Group),10 patients didn't accept pericardial infusion(Control Group).Results:The effects of IL-2 Group and Chemotherapy Group were almost the same,better than those in Control Group.Adverse reactions especially Degree III/IV bone marrow depression of IL-2 Group and Control Group were less than those in Chemotherapy Group.Conclusion:Treatment of malignant pericardial effusion with continuous pericardial drainage and infusion of IL-2 into the pericardial cavity has better effects,less adverse reactions and higher securities.

<正>原发性肝癌是我国常见的恶性肿瘤之一,其发病隐匿,早期症状不明显,临床有典型症状时,多属晚期,且病死率极高,近年来其发病有增高趋势。现对我院2007年1月～2010年10月间住院死亡的53例晚期原发性肝癌临床资料进行回顾性分析。1.材料与方法1.1病例来源中国医学科学院肿瘤医院2007年1月～2010年10月间共收治原发性肝癌患者2223例,死亡62例。排除早期肝癌、入院不足24小时、临床资料不完整者,共选取死亡的53例晚期肝癌进行研究。其中经病理学确诊为肝细胞癌9例,肝内胆管癌3例;经影像学临床诊断为原发性肝癌者41

目的 观察与分析经皮射频消融治疗老年肝脏恶性肿瘤的近期疗效和并发症.方法 2009年11月至2010年11月,采用B超引导经皮射频消融治疗老年肝脏恶性肿瘤患者32例.结果 32例均在术后12～20小时即可开始下床活动、进食.技术成功率96.88%(31/32).技术有效率100%(31/31),术后1个月肝脏增强CT/MRI检查示肿瘤完全凝固坏死.术后常见并发症:发热14例(43.75%),术后疼痛10例(31.25%),心律失常3例(9.38%),皮肤灼伤1例(3.13%).术后平均住院时间4天.结论 B超引导下经皮射频消融治疗老年肝脏恶性肿瘤具有简单、微创、安全、有效、并发症少等优点,严格把握适应证可以获得较好的疗效.

Objective To investigate the prognostic factors for breast cancer patients with brain metastasis.Methods From Jan.1999 to Dec.2009,89 patients with brain metastasis(BM) from breast cancer,who had both complete medical charts and follow-up data were eligible for this retrospective analysis.A number of potential factors which might affect prognosis were evaluated,including age,Karnofsky Performance Score(KPS),primary disease stage,ER,PR,HER-2 status,menses status,first sign of brain metastasis(BM),extension and numbers of BM lesions,control of primary tumor,presence of extracranial metastasis and sites of metastasis,chemotherapy,etc.Univariate analysis by Kaplan-Mierer combining with log-rank test and multivariate Cox regression model was used to determine the significance of prognostic variables in the survival.Results The mean age of 89 patients was 49.0 years(range 23-74 years).The median survival time was 8.6 months(range 0.2-61.5 months).Among 89 patients,the 1-year survival rate and mediean survival were significantly lower in patients with HER-2-positive tumors than in patients with HER-2-negative tumors(1-year survival rate:12.5% vs 46.2%,P=0.003,mediean survival: 6.3 months vs 10.9 months,P=0.003).The 1-year survival rate and median survival time were significantly lower in patients whose Karnofsky performance score was less than 60 than in patients whose Karnofsky performance score was greater than 60(1-year survival rate:15.0% vs 43.5%,P=0.017,median survival time:5.3months vs 10.1months,P=0.019).The 1-year survival rate and median survival time were significantly better in the patients who used hormonal therapy than in the patients who had not used hormonal therapy(1-year survival rate:66.7% vs 32.5%,P=0.027,median survival time:29.3 months vs 8.5 months,P=0.003).The patients who had received comprehensive treatments had got better outcome than those who hadn′t received comprehensive treatment(1-year survival rate:48.1% vs 21.6%,P=0.014,mediean survival time:13.6 months vs 6.0 months,P=0.006).In the Cox multivariate analysis,KPS,HER-2 status and comprehensive treatments were significant prognostic factors.Conclusions KPS,HER-2 status and comprehensive treatments were independent prognostic factors.