IMRT联合TP方案治疗晚期食管鳞癌的临床疗效及对患者血清MMP2、TIMP2、nm23-H1及不良反应的影响

目的分析调强放射治疗(IMRT)联合TP方案治疗晚期食管鳞癌的临床疗效及对患者血清基质金属蛋白酶2(MMP2)、组织金属蛋白酶抑制剂2(TIMP2)、nm23-H1及不良反应的影响。方法选取晚期食管鳞癌患者80例为研究对象,按随机数字表法将其分为观察组(n=40,采用IMRT联合TP方案化疗)、对照组(n=40,单纯采用IMRT治疗),比较2组临床疗效、治疗前后血清MMP2、TIMP2、nm23-H1表达阳性率、局控率与生存情况及不良反应。结果观察组治疗有效率(85.00%)明显高于对照组(65.00%)(P<0.05)。治疗后2组血清MMP2表达阳性率下降,而TIMP2、nm23-H1表达阳性率上升,且观察组治疗后血清MMP2表达阳性率低于对照组,而TIMP2、nm23-H1表达阳性率高于对照组(P<0.05)。观察组治疗后1年、2年局控率高于对照组,但2组治疗后1年、2年生存率差异无统计学意义(P>0.05)。观察组白细胞减少、放射性食管炎发生率高于对照组(P<0.05),2组其他不良反应发生率差异无统计学意义(P>0.05)。结论晚期食管癌患者采用IMRT联合TP方案治疗可获得较好的疗效,对患者血清MMP2、TIMP2、nm23-H1有明显改善,但可能会较单纯IMRT治疗具有更多不良反应,需加以监测。     

Characteristics and risk factors of bortezomib induced peripheral neuropathy: A systematic review of phase III trials

Bortezomib-induced peripheral neuropathy (BIPN) is a common toxicity associated with the treatment of multiple myeloma (MM), typically requiring dose reduction, delay, or cessation of treatment protocol. This systematic review aimed to investigate risk factors, trends, and variability associated with the development of BIPN. Searches were undertaken using Medline, PubMed, Cochrane Central Register of Controlled Trials, Embase, Scopus, and Web of Science. Additional studies were identified by investigating authors' bibliographic references cited by original and review articles. Articles that reported on neuropathy in phase III randomised control trials involving bortezomib in any treatment arm for the treatment of MM were included in this review. A total of 43 full text articles met criteria, which examined 23 phase III trials (N = 8218). Overall incidence of neuropathy ranged from 8.4% to 80.5% (median = 37.8%) and severe neuropathy (grade 3-4) ranged from 1% to 33.2% (median = 8%). Similar reports of neuropathy of any grade and severe neuropathy were observed between the newly diagnosed and relapsed cohort. Bortezomib regimens with reduced dose intensity were associated with reduced neuropathy incidence. Increased cumulative dosing levels, intravenous compared with subcutaneous administration and combination therapy with thalidomide were associated with higher rates of BIPN. This analysis revealed that BIPN is a significant toxicity. More sensitive measures are required to capture the incidence and severity of BIPN. Better understanding of risk factors and reversibility profiles will minimise the number of cancer survivors living with residual treatment side effects.     

抗PD-1/PD-L1免疫检查点抑制剂的皮肤免疫相关不良反应的研究进展

随着免疫检查点抑制剂（immune checkpoint inhibitors,ICPI）在国内外临床试验和应用中的逐步推广,越来越多的患者从免疫治疗中获得显著的疗效。其中抗程序细胞死亡蛋白1（programmed death-1,PD-1）及其配体（PD-1 ligand,PD-L1）免疫检查点抑制剂已被美国食品药品管理局（FDA）批准用于恶性黑色素瘤、转移性鳞状非小细胞肺癌、晚期肾癌、头颈鳞状细胞癌、尿路上皮癌等肿瘤的治疗。但PD-1/PD-L1单抗也会引起免疫相关性皮肤、消化道、肝脏、内分泌、肺部等器官的不良反应,皮肤毒性如皮疹、白癜风、皮肤干燥症等是最常见也是最早发生的不良反应。     

索拉非尼治疗转移性肾癌疗效与不良反应的关系

目的:探索索拉非尼在治疗转移性肾细胞癌（mRCC）患者中的不良反应与疗效之间的关系。方法:回顾性研究西京医院接受索拉非尼治疗的mRCC患者63例,利用卡方检验分析肿瘤控制率与不良反应的发生频率和严重程度的相关性,利用Kaplan-Meier方法分析16种不良反应,筛选出与患者PFS,OS相关的不良反应,将P＜0.05变量纳入多变量Cox比例风险回归模型进行进一步的多因素分析,确定独立预后因素。结果:63例接受索拉非尼治疗的患者中,完全缓解2例（3.2％）,部分缓解16例（25.4％）,疾病稳定37例（58.7％）,疾病进展8例（12.7％）。中位PFS为12.0个月,中位OS为24.0个月。卡方检验结果示肿瘤控制率与不良反应的发生频率和严重程度相关（均P＜0.05）。多变量分析显示,更好的PFS的独立预后因素包括腹泻（OR 0.255,95％CI 0.130~0.500,P=0.000）和皮疹（OR 0.235,95％CI 0.114~0.482,P=0.000）。OS的独立预后因素包括腹泻（OR 0.454,95％CI 0.246~0.839,P=0.012）,皮疹（OR 0.405,95％CI 0.211~0.776,P=0.006）和高血压（OR 0.373,95％CI 0.177~0.784,P=0.009）。结论:索拉非尼治疗mRCC患者的疗效与不良反应的发生频率和严重程度呈正相关。皮疹和腹泻是影响PFS的独立保护因素,皮疹,腹泻和高血压是影响OS的独立保护因素。这一结论仍需大量前瞻性研究证实。     

The role of immunosuppressive agents in the management of severe and refractory immune‐related adverse events

The advent of immune checkpoint inhibitors has improved survival in some types of cancer and brought promising prospects to cancer immunotherapy. Despite their clinical benefits, significant off‐target toxicities resulting from the immune system activation have been observed, namely immune‐related adverse events (irAEs), which pose to clinicians a new challenge of optimal management. With steroids being the mainstay of current management of irAEs, immunosuppressive agents are especially indicated for severe or steroid‐refractory cases, based on current immunopathophysiological knowledge and on extrapolations of treatment options for primary autoimmune disorders. This review focuses on the status and recent clinical progress of immunosuppressive agents in the management of severe and steroid‐refractory irAEs.     

Predictors of response and survival in patients with unresectable hepatocellular carcinoma treated with nivolumab: real-world experience

Real-world predictors of the treatment efficacy of immune checkpoint inhibitors for hepatocellular carcinoma (HCC) are unknown. This retrospective study enrolled 87 consecutive patients with unresectable HCC from May 2017 to December 2019 at two hospitals. Of the 87 patients, 7, 9, 60, and 11 patients had Barcelona Clinic Liver Cancer stages A, B, C, and D, respectively, and 45, 30, and 10 patients were Child-Pugh class A, B, and C, respectively. The median injection numbers of nivolumab and treatment duration were 6 (3-8) and 2.53 (1.47-4.23) months, respectively, and 64.4% of patients received combination therapy. Radiological imaging was not assessed for 25 patients. Objective response (OR) and disease control rates were 19.5% and 39.1%, respectively. A single tumor (odds ratio: 9.542, P = .015) and ≥20% decline in serum α-fetoprotein protein (AFP) levels within the first 3 months of treatment (defined as AFP response, odds ratio: 5.997, P = .042) were predictors of OR. Lack of macrovascular invasion, combination therapy, and AFP response were predictors of progression-free survival. A Cancer of the Liver Italian Program (CLIP) score of 0-2 (hazard ratio [HR]: 3.717, P = .004) and grade 1-2 immune-related adverse events (irAEs, HR: 2.217, P = .049) were predictors of overall survival (OS) in the entire cohort, and a CLIP score of 0-2 (HR: 3.257, P = .009) was a predictor of OS in evaluable patients. IrAEs ≥ grade 3 were noted in 14 patients, and three died as a result. Having a single tumor and AFP response were predictors of OR, and CLIP score was a predictor of OS.     

不同措施干预心肌梗死患者PCI术中无复流现象的远期疗效

目的研究不同干预措施对ST段抬高心肌梗死(STEMI)患者经皮冠状动脉介入术(PCI)中无复流现象的远期疗效。方法入选接受过PCI术无复流预防及治疗措施且有完整随访资料的127例STEMI患者,其中PCI术前采用Diver CE血栓抽吸导管患者34例(抽吸预防组),冠状动脉内及静脉应用替罗非班患者34例(替罗非班预防组),PCI术中发生无复流现象的患者中应用替罗非班18例(替罗非班治疗组),应用替罗非班+血塞通18例(替罗非班+血塞通组),应用腺苷11例(腺苷组),应用维拉帕米12例(维拉帕米组)。随访及分析患者18个月及36个月时发生心绞痛再发、心肌梗死再发、心力衰竭、心源性死亡等主要心脏不良事件(MACE)。结果抽吸预防组、替罗非班预防组、替罗非班治疗组、替罗非班+血塞通组、腺苷组、维拉帕米组六组127例患者随访18个月时,心力衰竭发生率分别为5.9%、17.6%、33.3%、27.8%、45.4%、50.0%;MACE发生率分别为8.8%、29.4%、50.0%、38.9%、63.6%、66.7%。抽吸预防组心力衰竭发生率和MACE发生率最低,与其他各组比较有统计学差异(P0.05);替罗非班预防组心力衰竭发生率和总体MACEs发生率低于腺苷组和维拉帕米组,差异有统计学意义(P0.05);替罗非班治疗组、替罗非班+血塞通治疗组、腺苷组和维拉帕米组四组47例患者随访36个月时,各组间MACEs发生率无统计学差异(P0.05)。结论冠状动脉内血栓负荷重的STEMI患者,PCI术前应用血栓抽吸导管有较好的远期疗效;替罗非班、替罗非班联用血塞通、腺苷、维拉帕米几种药物治疗无复流现象远期疗效相似。