PD-1单抗治疗晚期肿瘤的临床疗效

目的:观察PD-1单抗治疗晚期肿瘤的临床疗效及安全性。方法:回顾性分析PD-1单抗治疗48 例晚期肿瘤患者的临床效果,评价其客观有效率、无疾病进展生存期、总生存期及不良反应。结果:48 例患者在接受PD-1单抗2周期治疗后,完全缓解（CR）0例,部分缓解（PR）3例,疾病稳定（SD）33例,疾病进展（PD）12例,客观有效率（ORR）为6.25%,疾病控制率（DCR）为75%。截至随访结束,33例出现无进展生存期（PFS） 终点事件,12例出现总生存期（OS）终点事件,全组客观有效率（ORR）为6.25%,疾病控制率（DCR）为75%,中位 PFS 为106.5天,中位OS为185天。肺癌亚组客观有效率（ORR）为4.55%,疾病控制率（DCR）为81.8%,中位PFS为106.5天,中位OS为202天。全组不良反应发生率为 31.2%,主要为恶心呕吐7 例（14.5%）,骨髓抑制5例（10.4%）,发热2例（4.2%）,皮疹1例（2.1％）,肝功能损害 2例（4.2％）。结论:PD-1单抗治疗晚期肿瘤具有一定疗效,患者耐受性良好。     

中晚期肝癌多纳非尼联合抗PD-1单抗、HAIC治疗成功转化1例

<正>肝癌是一种临床常见的严重威胁人类健康的消化系统肿瘤。2020年肝癌发病率位居恶性肿瘤第6位,死亡率位居癌症相关死亡第3位^[1]。肝癌早期缺乏典型症状,治疗效果较差,靶向治疗、免疫治疗和介入治疗是中晚期肝癌系统治疗的重要组成部分^[2]。国内一项Ⅲ期临床研究显示,索拉非尼联合FOLFOX 4方案肝动脉灌注化疗(hepatic artery infusion chemotherapy,HAIC)可将合并门静脉癌栓肝癌患者的生存期延长近一倍^[3]。我院收治的1例中晚期肝癌患者经多纳非尼联合抗PD-1单抗、FOLFOX方案HAIC治疗3个月转化成功,现将该病例治疗经过报告如下。     

PD-1治疗晚期原发性肝癌患者的安全性及临床疗效观察CSCD

目的观察PD-1治疗晚期肝癌患者的近期临床疗效及总生存期。方法回顾性分析48例PD-1(观察组)治疗及55例甲磺酸阿帕替尼(对照组)治疗晚期肝癌患者的临床资料,分析患者近期临床疗效、总生存期和不良反应。结果观察组AFP、ALT、AST、ECOG、Child-Paugh评分、客观缓解率及疾病控制率优于对照组(P<0.05),且观察组患者的生存期(95%CI:7.24~8.64月)明显高于对照组(95%CI:5.13~6.39月)(P<0.05)。两组间皮疹、恶心呕吐及高血压不良反应差异有统计学意义(P<0.05)。结论PD-1较甲磺酸阿帕替尼可改善晚期肝癌患者近期临床疗效及延长晚期肝癌患者总生存期。     

PD-1抑制剂联合靶向药物治疗晚期原发性肝癌的安全性及临床疗效观察

目的:探讨PD-1抑制剂联合靶向药物治疗晚期原发性肝癌的安全性及有效性。方法:选取2020至2021年本院收治的70例晚期原发性肝癌患者作为研究对象,分为两组,分别予以单药PD-1抑制剂治疗（单药治疗组）、PD-1抑制剂联合靶向药物治疗（联合用药组）,并对两组患者的相关病历资料及获取的有效性及安全性数据行回顾性分析。结果:安全性比较可知,单药治疗组发生不良事件的比率分别为皮肤及皮下组织类疾病占17.14%,肝功能异常占25.71%,血液学毒性占31.42%,全身性症状占8.57%,胃肠道占17.14%,呼吸系统、胸及纵隔疾病占11.43%,代谢及营养类疾病占20.00%,肾脏及泌尿系统疾病占5.71%,内分泌系统疾病占5.71%;联合用药组发生不良事件的比率分别为皮肤及皮下组织类疾病占22.85%,肝功能异常占28.57%,血液学毒性占25.71%,全身性症状占11.43%,胃肠道占20.00%,呼吸系统、胸及纵隔疾病占14.29%,代谢及营养类疾病占17.14%,肾脏及泌尿系统疾病占8.57%,内分泌系统疾病占2.86%,两组比较差异均无统计学意义（P＞0.05）,联合用药并不会增加不良事件发生。有效性比较可知,单药治疗组患者的完全缓解率为8.57%、部分缓解率为31.43%、疾病稳定率为48.57%、疾病进展率为11.43%;联合治疗组患者的完全缓解率为14.29%、部分缓解率为54.29%、疾病稳定率为25.71%、疾病进展率为5.71%,差异具有统计学意义（P＜0.05）。联合用药组对疾病更为有效。T淋巴细胞水平高于单药组（P＜0.05）。结论:对晚期原发性肝癌患者行PD-1抑制剂联合靶向药物治疗比单药PD-1抑制剂提升T淋巴细胞水平,治疗能取得更好的临床效果,保证患者足够的安全性。     

抗EGFR单抗治疗相关皮肤不良反应临床处理专家共识

抗表皮生长因子受体(epidermal growth factor receptor,EGFR)单抗已成为转移性结直肠癌治疗的重要手段之一.皮肤不良反应是抗EGFR单抗的主要不良反应,具体包括丘疹脓疱型皮疹、甲沟炎及皮肤干燥瘙痒等,极大影响患者的生活质量和治疗依从性.基于指导抗EGFR单抗治疗相关的皮肤不良反应处理的临...     

113例原发性肝癌的临床病理分析

目的:探讨原发性肝癌临床及病理学特征。方法:对113例原发性肝癌的临床资料和病理资料进行回顾性分析。结果:113例原发性肝癌有91例为肝细胞癌,22例为胆管癌。91例肝细胞癌患者均为乙肝患者,其中86例伴发结节性肝硬化,87例AFP阳性;组织学类型小梁型56例,假腺型15例,实体型20例。22例胆管癌患者仅1例有乙肝病史,3例合并肝血吸虫病,5例合并胆管炎症或结石。结论:肝细胞癌与乙肝病毒感染密切相关,常见于结节性肝硬化患者,大部分患者AFP阳性,组织学类型以小梁型为主。胆管癌多见于女性,通常无肝硬化,与血吸虫感染或胆管炎症有较密切关系。     

晚期非小细胞肺癌PD-1/PD-L1单抗治疗临床转化现状

随着对肿瘤免疫逃逸机制研究的不断深入,通过阻断程序性死亡因子1（programmed cell death 1,PD-1）及其配体l （PD-1 ligand,PD-L1）构成的 PD-1/PD-L1 通路,证实了 PD-1/PD-L1 抑制剂在晚期非小细胞肺癌（non small cell lung cancer, NSCLC）患者生存的相关性,以及PD-L1作为疗效预测标志物的价值。在NSCLC的局部晚期维持治疗、二线治疗及部分一线治 疗的临床试验中,PD-1/PD-L1抑制剂治疗均获得了较好的治疗效果;PD-1/PD-L1抑制剂联合放化疗、联合细胞因子与其他免疫 抑制剂及联合细胞外调节蛋白激酶(extracel lular regulated protein kinase,ERK)通路靶向治疗也有一定获益。本文就PD-1/PD-L1 抑制剂用于NSCLC治疗现状及其影响因素作一综述。     

PD-1/PD-L1单抗联合放疗治疗实体瘤研究进展

PD-1/PD-L1单抗联合放疗可增强抗肿瘤免疫效应,在部分实体瘤临床前试验中疗效显著,有望成为有效的临床治疗模式。PD-1/PD-L1单抗联合放疗的作用机制、联合时机、放疗分割模式与放疗剂量等是本类研究的重点。本文就PD-1/PD-L1单抗联合放疗治疗实体瘤的研究进展进行综述。     

抗人stathmin单克隆抗体与紫杉醇联用对人肝癌细胞增殖的抑制作用

目的: 探讨抗人stathmin单克隆抗体和紫杉醇单用或联用对肝癌细胞系HepG2增殖的抑制作用。方法: 以不同浓度的抗人stathmin单克隆抗体、紫杉醇分别组成单药组和联合用药组, 另设不加药的空白对照组,分别作用于HepG2细胞24、48、72和96 h,观察细胞数量和形态的变化,MTT法检测各用药组对HepG2细胞增殖的抑制作用,AnnexinV/PI双染法检测各组细胞凋亡率的改变。结果: 不同浓度的各组药物作用后细胞数量明显减少,形态不规则,部分细胞变圆、细胞核固缩和胞质减少,而对照组细胞生长状态良好。抗人stathmin单克隆抗体、紫杉醇单药与联用均能抑制HepG2细胞增殖, 呈剂量时间依赖效应, 联用组细胞增殖抑制率较单药组明显增高(P<0.05),两药联用有交互效应( P<0.05)。抗人stathmin单克隆抗体、紫杉醇单用与联用均能诱导HepG2细胞凋亡, 联合组作用更为明显(P<0.05)。结论: 抗人stathmin单克隆抗体、紫杉醇单药与联用均能抑制HepG2细胞增殖和诱导其凋亡,两药联合使用具有协同作用。     

低剂量阿帕替尼治疗卡瑞利珠单抗致反应性毛细血管增生症的疗效分析

  目的  评价低剂量阿帕替尼治疗卡瑞利珠单抗致反应性毛细血管增生症（reactive cutaneous capillary endothelial proliferation,RCCEP）的疗效和安全性。   方法  回顾性分析不同抗血管生成药物联合卡瑞利珠单抗治疗晚期实体肿瘤140例的RCCEP发生率。观察250 mg和125 mg阿帕替尼两个剂量组治疗50例单药卡瑞利珠单抗诱发RCCEP的疗效和安全性。  结果  140例晚期实体瘤使用卡瑞利珠单抗联合不同抗血管生成药物的RCCEP发生率:贝伐珠单抗组为93.3%,安罗替尼组为72.7%,呋喹替尼组为47.6%,瑞戈非尼组为70.6%,阿帕替尼组为14.0%。阿帕替尼较其它抗血管生成药物显著降低RCCEP发生率:贝伐珠单抗组 vs. 阿帕替尼组（P<0.000 1）;安罗替尼组 vs. 阿帕替尼组（P<0.000 1）;呋喹替尼组 vs. 阿帕替尼组（P=0.005）;瑞戈非尼组 vs. 阿帕替尼组（P<0.000 1）。观察50例晚期实体瘤不同剂量阿帕替尼治疗卡瑞利珠单抗诱发RCCEP的疗效和安全性,结果提示42例250 mg阿帕替尼治疗组有效率为97.6%,8例125 mg阿帕替尼治疗组有效率为87.5%;两个剂量组均未出现≥G3的治疗相关不良事件。   结论  阿帕替尼较其它抗血管生成药物更显著降低卡瑞利珠单抗的RCCEP发生率,低剂量阿帕替尼可有效安全地缓解RCCEP。      

PD-1抑制剂治疗肝细胞癌疗效相关生物标志物的研究现状

近年来免疫治疗在肝细胞癌辅助治疗领域取得了初步成果,而程序性死亡受体1(Programmed cell death-1,PD-1)抑制剂是目前的研究热点,然而其总反应率仍不尽如人意,因此目前急需寻找合适的生物标志物,来预测PD-1抑制剂治疗肝细胞癌患者的疗效,本文就PD-1抑制剂治疗肝细胞癌的相关生物标志物的研究进展进行综述。     

Serotherapy of L1210 murine leukaemia--reasons for ineffectiveness of in vivo treatment by L.1 monoclonal antibody.

A monoclonal antibody (L.1), reacting in vitro specifically with L1210 leukaemia cells in a complement-dependent cytotoxicity assay (CDC), has been exploited for serotherapy studies. Different regiments of L.1 treatment of CD2F1 mice bearing the semi-syngeneic L1210 leukaemia did not prolong the life span of tumor-bearing animals. Moreover, the administration of L.1 did not enhance the antitumour effects of cyclophosphamide. Studies of in vivo localization showed that L.1 was able to bind specifically to L1210 leukaemic cells, although 30-40% of the cells remained negative. The presence of L.1 in mouse blood was demonstrated up to 15 days after the inoculation. On the other hand, in vivo administration of L.1 was probably accompanied by loss of the cytotoxic activity, perhaps through a mechanism of complement inactivation, since the presence of undiluted normal mouse serum in a CDC assay inhibited the cytotoxic activity of L.1. Moreover, serum from L.1-treated mice did not display any cytotoxic activity, although the presence of the antibody could be demonstrated by indirect immunofluorescence. Shedding of the antigen defined by L.1 was probably not responsible for the failure of the serotherapy, since the L.1 neutralizing antigen could be found in body fluids only long after the start of therapy.     

Regional hyperthermia in the treatment of primary hepatic carcinoma

BACKGROUND AND OBJECTIVES: The purpose of this research was to investigate the clinical significance of regional hyperthermia in the treatment of primary hepatic carcinoma (PHC). METHODS: The regional hyperthermia (60 degrees C) was used whenever there was suspicion of residual cancer tissues on the edge of the hepatic resection. The hyperthermia was maintained for about 5-20 min depending on the size and the amounts of residual nodulus. If there was obvious necrosis on the hyperthermia-treated site, the solidified tissues were removed. Otherwise, the solidified tissues were kept in situ. RESULTS: There were 68 cases of PHC patients in this study. The patients were divided into 4 groups: A, lobectomy, 14 cases; B, lobectomy plus regional hyperthermia, 12 cases; C, regional hepatectomy, 16 cases; D, regional hepatectomy plus regional hyperthermia, 26 cases. All patients were followed after their operations. The mean survival time of the 4 groups was as follows: Group A, 346.5 days (186-921 days); Group B, 432.6 days (254-1189 days); Group C, 525.4 days (192-1016 days); and Group D, 1142 (from 318 days to seven years and two months) days. There were significant differences between Groups A and B (P < 0.01) and between Groups C and D (P < 0.01). It seems that regional hyperthermia on the hepatic resection edge can prolong patients' survival time. CONCLUSIONS: Regional hyperthermia on the hepatic resection edge is helpful for prolonging patients' survival time in the treatment of primary hepatic carcinoma.     

Evaluation on a six-dose treatment of anti CD 20 monoclonal antibody in patients with refractory follicular lymphoma

Treatment of refractory follicular lymphoma with monoclonal antibody CD 20 has been proven to be a good therapeutic option. However, most studies used four weekly doses and time to treatment failure (TTF) and overall survival (OS) could be considered very short: 11.0 and 13.6 months respectively. We started a pilot study to evaluate if six infusions at the same doses and schedule could improve the outcome in these patients. Seventeen patients with refractory follicular lymphoma heavily treated with chemotherapy (> 2 regimens), radiotherapy and biological modifiers were enrolled in a pilot study. They received 6 weekly doses, at 375 mg/m2, of monoclonal anti CD 20. In an intent to treat analysis, overall response was 76%, of which 47% (8 patients) were complete response and 5 patients were partial response. With a median follow-up of 28.6 months, 7 complete responders remain alive, free of disease, and 2 partial responses remain stable without additional treatment. Median to TTF has not been reached; yet, actuarial curves showed that at 3 years, 53% of patients are alive. The four patients who were failure died secondary to tumor progression. Overall survival (OS) at 3-year was 76%. Toxicity was mild, all patients completed the schedule on time and doses. The addition of two doses of anti CD 20 clearly improved OS and TTF in a group of patients with refractory follicular lymphoma heavily treated and with poor prognostic factors. However, the number is too short to draw definitive conclusions; more clinical trials are necessary to determine if 4 or 6 doses of anti CD 20 therapy are better in this setting of patients.     

放疗联合肝动脉栓塞化疗治疗原发性肝癌的研究进展

放疗和介入是目前不能切除的晚期原发性肝癌(PHC)患者的主要治疗方法,但由于各自适应证的限制影响其有效率.放疗技术的进步,特别是放疗联合肝动脉栓塞化疗(TACE)在肝癌治疗中的应用,为患者提供了更佳的治疗手段.     

肝动脉化疗栓塞治疗原发性肝癌的预后因素分析

目的：探讨影响肝动脉化疗栓塞治疗原发性肝癌预后的相关因素,为原发性肝癌患者选择个体化治疗方案及估计预后提供参考。方法：回顾性分析2003年6月-2012年6月石河子大学医学院第一附属医院实施肝动脉化疗栓塞的153例患者的临床资料及随访数据,生存分析采用生命表法,相关因素分析行 Log -rank 检验,多因素分析采用 Cox 模型,筛选出影响预后的因素。结果：随访至2013年6月30日153例患者失访15例（9.8%）,原发性肝癌患者经肝动脉化疗栓塞后1、3、5年生存率分别为55.92%、31.02%、21.18%。单因素分析结果显示肝功能分级、甲胎蛋白（AFP）、肿瘤大小、肿瘤数目、门脉癌栓及治疗次数是影响预后的因素;Cox 风险回归分析显示肝功能分级、肿瘤数目、门脉癌栓及治疗次数是影响预后的独立因素（P <0.05）。结论：肝功能分级、肿瘤数目、门脉癌栓为影响原发性肝癌介入治疗预后的独立危险因素,而治疗次数是影响预后的保护性因素。