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中华肿瘤杂志
中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院
中华肿瘤杂志

中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院

赵平

月刊

0253-3766

chinjoncol@yahoo.com.cn

010-87788229

100021

北京市朝阳区潘家园南里17号

中华肿瘤杂志/Journal Chinese Journal of OncologyCSCD北大核心CSTPCD
查看更多>>1979年创刊，中国科学技术协会主管，中华医学会主办。本刊是肿瘤专业学术期刊，始终坚持基础与临床相结合的方针，以我国肿瘤防治研究工作的主要成就、进展及新动向为报道重点，记载了我国防癌、抗癌事业的发展历程，展现了我国防癌、抗癌事业所取得的辉煌成就。《中华肿瘤杂志》已被Medline等14个数据库和25个文摘期刊收录。1999年获第一届国家期刊奖提名奖。1992—2002年连续三次获得中国科协优秀学术期刊奖。2001—2010年连续九次获“百种中国杰出学术期刊”称号。被中国自然科学核心期刊研究课题组评为中国自然科学核心期刊，被中国国家新闻出版总署定为中国期刊方阵双奖期刊。
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    非小细胞肺癌表皮生长因子受体20号外显子插入突变检测临床实践中国专家共识（2024版）

    应建明王洁殷宝侠
    179-188页
    查看更多>>摘要：中国肺癌人群中约82%为非小细胞肺癌，表皮生长因子受体（EGFR）基因则是中国肺癌人群中最常见的驱动基因突变（51.7%～54.4%）。近年来靶向治疗特别是EGFR酪氨酸激酶抑制剂的快速发展及广泛应用显著提高了中国肺癌患者的生存时间及生存质量。EGFR基因20号外显子插入突变（EGFR ex20ins）在中国非小细胞肺癌患者中发生率约为0.3%～2.9%，居EGFR基因突变第3位，目前已有多个针对性靶向药物研发。然而EGFR ex20ins的变异类型众多，具有高度分子异质性，检测难度较高，临床检测需进一步规范。明确EGFR ex20ins检测临床意义、适用人群及不同检测方法优劣势，规范报告内容，对提高EGFR ex20ins检测准确性具有重要意义。针对EGFR ex20ins检测的实际问题，中国抗癌协会肿瘤病理专业委员会分子病理协作组和中国医师协会肿瘤多学科诊疗专业委员会结合国内外多中心研究及临床实践经验，组织专家讨论并制定了非小细胞肺癌EGFR ex20ins检测临床实践中国专家共识（2024版），以期指导临床EGFR ex20ins检测实践。 About 82% of the Chinese lung cancer population is non-small cell lung cancer(NSCLC), and the epidermal growth factor receptor (EGFR) gene is the most common driver mutation in the Chinese lung cancer population (51.7%-54.4%). In recent years, the rapid development and wide application of targeted therapies, especially EGFR tyrosine kinase inhibitors, have significantly improved the survival time and quality of life of Chinese lung cancer patients. EGFR exon20 insertion (EGFR ex20ins) accounts for 0.3%-2.9% in NSCLC patients in China. Recently, several tyrosine kinase inhibitors have been approved for the therapy of EGFR ex20ins NSCLCs. The variety variants and high molecular heterogeneity of EGFR ex20ins NSCLCs asks for more accurate detection methods, and clinical routine detection process needs to be further standardized. On account to the practical questions of EGFR ex20ins detection, this consensus was finally reached based on the combination of literature, expert experience and internal discussion among committee members, in the hope of providing the guide for standardizing the EGFR ex20ins detection.

    肺肿瘤表皮生长因子受体基因20号外显子插入基因检测专家共识

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    伊鲁阿克治疗间变性淋巴瘤激酶融合基因阳性局部晚期或转移性非小细胞肺癌中国专家共识（2024版）

    石远凯殷宝侠
    189-205页
    查看更多>>摘要：间变性淋巴瘤激酶（ALK）融合基因是非小细胞肺癌（NSCLC）常见的驱动基因之一。流行病学数据显示，在中国晚期NSCLC患者中ALK融合基因的阳性率为9.06%。ALK酪氨酸激酶抑制剂（TKIs）已经成为ALK融合基因阳性晚期NSCLC患者的标准治疗选择。目前中国国家药品监督管理局已经批准7种ALK-TKIs上市，分别是克唑替尼、塞瑞替尼、阿来替尼、恩沙替尼、布格替尼、洛拉替尼和伊鲁阿克。伊鲁阿克是中国自主研发的新型ALK-TKI，2023年6月27日，国家药品监督管理局批准伊鲁阿克上市，用于既往接受过克唑替尼治疗后疾病进展或对克唑替尼不耐受的ALK融合基因阳性局部晚期或转移性NSCLC患者的治疗，2024年1月16日，国家药品监督管理局批准伊鲁阿克用于ALK融合基因阳性局部晚期或转移性NSCLC患者的一线治疗。为了帮助广大医师更好地了解伊鲁阿克的疗效和安全性，使伊鲁阿克得到更合理的临床应用，中国医疗保健国际交流促进会肿瘤内科学分会和中国医师协会肿瘤医师分会组织专家编写了《伊鲁阿克治疗间变性淋巴瘤激酶融合基因阳性局部晚期或转移性非小细胞肺癌中国专家共识（2024版）》。 Anaplastic lymphoma kinase (ALK) fusion gene is one of the most common driver gene in non-small cell lung cancer (NSCLC). Epidemiological data showed that ALK gene fusion is detected in 9.06% of Chinese advanced NSCLC patients. ALK-tyrosine kinase inhibitors (TKIs) have become the standard treatment for advanced NSCLC patients with ALK gene fusion. Seven different ALK-TKIs have been approved by the National Medical Products Administration (NMPA) of China, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, and iruplinalkib. Iruplinalkib is a novel new-generation ALK-TKI independently developed in China. On June 27, 2023, the NMPA approved iruplinalkib for the treatment of locally advanced or metastatic ALK-positive NSCLC patients whose disease has progressed after previous treatment with crizotinib or who are intolerant to crizotinib. On January 16, 2024, the NMPA approved iruplinalkib for the first-line treatment of locally advanced or metastatic ALK-positive NSCLC patients. In order to better understand the efficacy and safety of iruplinalkib, and facilitate more rationally clinical application of iruplinalkib, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists co-organized experts to compile the “Chinese expert consensus on iruplinalkib for the treatment of locally advanced or metastatic ALK-positive non-small cell lung cancer (2024 edition)”.

    肺肿瘤非小细胞癌间变性淋巴瘤激酶酪氨酸激酶抑制剂伊鲁阿克专家共识

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    肺癌第9版TNM分期解读

    张波方文涛钟华殷宝侠...
    206-210页
    查看更多>>摘要：流行病学数据显示，肺癌发病率位居恶性肿瘤第2位，死亡率位居恶性肿瘤第1位，2020年约180万例患者死于肺癌。对于晚期肺癌患者，驱动基因的发现及相应靶向药物的应用不仅改善了患者生活质量，同时提高了患者的生存时间。免疫检查点抑制剂的应用则革新了驱动基因突变阴性患者的治疗策略。TNM分期是包括肺癌在内的实体瘤应用最为广泛的分期系统，统一的分期方法不仅为国际间的学术交流提供了共同的学术语言，同时也为疾病的预后判断及后续治疗决策制定提供了重要的工具。随着对肺癌预后因素的深入认识及研究数据的不断积累和成熟，肺癌TNM分期不断更新。2023年9月在新加坡举行的世界肺癌大会上，第9版TNM分期向全球公布并预计在2024年1月正式采用。本文就肺癌TNM分期的历史沿革、数据来源、第9版分期的主要变化及局限性进行讨论。 Lung cancer is the second commonly diagnosed cancer and remained the leading cause of cancer-related death, with an estimated 1.8 million deaths in 2020. The identification of driver gene mutation and administration of corresponding tyrosine kinase inhibitor have improved overall survival and quality of life in advanced lung cancer patients. Check point inhibitor has revolutionized treatment strategy of driver gene negative advanced NSCLC patients. TNM staging system is the most widely used classification method, providing an international common language during academic communication and important tool for predicting prognosis and subsequent treatment decision making. Accumulating knowledge about prognostic factors in lung cancer promotes the update of TNM classification. In the World Conference on Lung Cancer (WCLC) held in Singapore, September, 2023, International Association for Study of Lung Cancer (IASLC) released the forthcoming 9th edition of TNM classification for lung cancer, which is supposed to be adopted at January, 2024. The manuscript discussed the history, data resource and limitation of the TNM staging system.

    肺肿瘤TNM分期国际肺癌研究协会

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    抗人表皮生长因子受体2抗体药物偶联物在人表皮生长因子受体2低表达泛瘤种中的治疗进展

    危彤袁芃殷宝侠
    211-220页
    查看更多>>摘要：抗体药物偶联物（ADCs）由靶向特异性抗原的单克隆抗体药物和小分子细胞毒药物通过连接子偶联而成，它结合了高特异性靶向能力和强效杀伤作用的优势，实现了对癌细胞的精准高效打击。目前ADCs是抗癌药物研发的热点之一。人表皮生长因子受体2（HER-2）是目前已知的一种原癌基因，可以驱动多种肿瘤类型的发生和发展，HER-2也是早期获批用于实体肿瘤ADCs的重要肿瘤靶点。抗HER-2的ADCs不仅可用于治疗HER-2阳性肿瘤，而且对HER-2低表达肿瘤也有效。ADCs的出现打破了肿瘤中HER-2传统分型，为HER-2低表达肿瘤带来了重大的治疗突破。抗HER-2的ADCs在实体瘤治疗中应用广泛，在HER-2低表达肿瘤中也有较多的循证医学证据。文章概述各个抗HER-2的ADCs在HER-2低表达泛瘤种（包括乳腺癌、消化道恶性肿瘤、尿路上皮癌、肺癌等）中的治疗进展，总结各个抗HER-2 ADCs目前临床前研究、临床研究及安全性等方面的研究现状，以期为HER-2低表达肿瘤的临床用药提供参考。 Antibody-drug conjugates (ADCs) are drugs that combine monoclonal antibody drugs targeting specific antigens and small molecule cytotoxic drugs through linker molecules. ADCs combine the advantages of high specificity targeting and potent killing effects, achieving precise and efficient targeting of cancer cells. Nowadays, ADCs are one of the hotspots in cancer drug development. Human epidermal growth factor receptor 2 (HER-2) is a known oncogene that can drive the occurrence and development of various types of tumors. HER-2 is also an important tumor target for ADCs approved for solid tumors. Anti-HER-2 ADCs can not only be used to treat HER-2-positive tumors but also effectively target HER-2-low tumors. The emergence of ADCs has broken the traditional classification of HER-2 in tumors, bringing significant treatment breakthroughs for HER-2-low tumors. Anti-HER-2 ADCs are widely used in the treatment of solid tumors and have substantial evidence for HER-2-low tumors. This article presents the progress of various anti-HER-2 ADCs in HER-2-low tumors including breast cancer, gastrointestinal malignancies, urothelial carcinoma, lung cancer. And this article summarizes the current status of preclinical studies, clinical studies, and safety of anti-HER-2 ADCs in order to provide reference for the clinical use of HER-2-low tumors.

    恶性肿瘤抗体药物偶联物人表皮生长因子受体2低表达靶向治疗

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    2022年中国恶性肿瘤流行情况分析

    郑荣寿陈茹韩冰峰王少明...
    221-231页
    查看更多>>摘要：目的 根据全国肿瘤登记中心收集的肿瘤登记数据，估计2022年中国恶性肿瘤流行情况。 方法 纳入700个肿瘤登记处的2018年数据和106个登记处的2010—2018年数据，采用年龄-时期-队列模型，按性别、城乡分层，估计2022年总体及23类主要恶性肿瘤的中国人口年龄标准化发病率（中标发病率）和死亡率（中标死亡率）。结合2022年人口数据，估计2022年中国恶性肿瘤发病和死亡例数。 结果 2022年中国恶性肿瘤新发病例估计为482.47万（男性253.39万，女性229.08万），中标发病率为208.58/10万（男性212.67/10万，女性208.08/10万）。城市地区恶性肿瘤新发病例约290.39万，中标发病率为212.95/10万；农村地区192.08万，中标发病率为199.65/10万。发病例数前5位的恶性肿瘤（肺癌106.06万，结直肠癌51.71万，甲状腺癌46.61万，肝癌36.77万，女性乳腺癌35.72万）占全部新发病例的57.4%。2022年中国恶性肿瘤死亡病例估计为257.42万（男性162.93万，女性94.49万），中标死亡率为97.08/10万（男性127.70/10万，女性68.67/10万）。城市地区恶性肿瘤死亡病例约140.06万，中标死亡率为92.37/10万；农村地区117.34万，中标死亡率为103.97/10万。死亡例数前5位的恶性肿瘤（肺癌73.33万，肝癌31.65万，胃癌26.04万，结直肠癌24.00万，食管癌18.75万）占全部死亡病例的67.5%。肺癌居男、女恶性肿瘤发病和死亡首位，城市地区恶性肿瘤发病率高于农村地区，死亡率低于农村地区。 结论 中国恶性肿瘤疾病负担存在性别、城乡和地区差异，总体呈现发达国家与发展中国家癌谱共存的局面，防控形势严峻。 Objective The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center. Methods According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022. Results The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas. Conclusions The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.

    恶性肿瘤肿瘤登记发病率死亡率中国

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    广东省中山市1970—2014年恶性肿瘤净生存率分析

    李柱明梁智恒刘宁魏矿荣...
    232-238页
    查看更多>>摘要：目的 分析广东省中山市1970—2014年恶性肿瘤生存资料，为中山市肿瘤防控提供科学依据。 方法 广东省中山市1970—2014年恶性肿瘤发病资料来源于中山市肿瘤登记处，随访截至2019年12月31日。统计指标包括总体和主要恶性肿瘤不同时期的标化5年净生存率及其年度变化百分比（APC）和平均年度变化百分比（AAPC）。标化生存率采用国际癌症生存标准年龄结构进行加权。 结果 广东省中山市1970—2014年符合研究条件的恶性肿瘤新发病例共78 854例，其中肺癌（13 466例，17.08%）、鼻咽癌（9 715例，12.32%）和肝癌（9 707例，12.31%）较多，总体病理学诊断比例（MV%）为69.87%，主要恶性肿瘤MV%在21.07%～97.00%之间。2010—2014年，中山市恶性肿瘤总体、男性、女性的标化5年净生存率分别为39.74%、30.92%和52.47%，主要恶性肿瘤标化5年净生存率分别为甲状腺癌97.98%，脑及中枢神经系统肿瘤74.29%，鼻咽癌73.92%，结直肠癌50.23%，女性乳腺癌81.38%，子宫体癌78.81%，宫颈癌68.57%，前列腺癌49.33%，肺癌16.19%，肝癌12.14%，食管癌11.78%。1970—2014年，中山市总体恶性肿瘤标化5年净生存率呈上升趋势（AAPC=1.5%，P=0.025），不同时期女性恶性肿瘤标化5年净生存率均高于男性。 结论 1970—2014年广东省中山市总体及主要恶性肿瘤的标化5年净生存率呈上升趋势，但与全球CONCORD-3项目参与国家和地区相比，近期净生存率仍处于中低水平，提示中山市应继续加强肿瘤防控。 Objective To analyze survival data of cancer from 1970 to 2014 in Zhongshan City, Guangdong Province, and provide scientific basis for cancer prevention and control in Zhongshan City. Methods The tumor incidence data of Zhongshan City, Guangdong Province from 1970 to 2014 were collected from Zhongshan Cancer Registry, and all patients were followed up to December 31, 2019. The standardized 5-year net survival rates and their annual percentage change (APC) and average annual percentage change (AAPC) for total and major cancers at different times were used to describe statistical analysis. The standardized survival rates were weighted using the International Cancer Survival Standard Age Coefficients. Results There were 78 854 cancer patients eligible for the study in Zhongshan City of Guangdong Province from 1970 to 2014, among which lung cancer (13 466 cases, 17.08%), nasopharyngeal cancer (9715 cases, 12.32%) and liver cancer (9707 cases, 12.31%) were the main types of cancer. The morphology verification was 69.87% in the whole of cancers and the ranges were 21.07% to 97.00% in major cancers. From 2010 to 2014, the 5-year age-standardized net survival rates of cancers for all, males and females in Zhongshan City were 39.74%, 30.92% and 52.47%, in which were 97.98% for thyroid cancer, 74.29% for brain and central nervous system tumors, 73.92% for nasopharyngeal cancer, 50.23% for colorectal cancer, 81.38% for female breast cancer, 78.81% for uterine body cancer, 68.57% for cervical cancer, 49.33% for prostate cancer, 16.19% for lung cancer , 12.14% for liver cancer, and 11.78% for esophageal cancer, respectively. The survival rates of all cancers in Zhongshan City showed an increasing trends in 1970-2014 (AAPC=1.5%, P=0.025), and it was higher in female cancers than that of male in all periods. Conclusion The standardized 5-year net survival rates of all and major cancers in Zhongshan City of Guangdong Province show an increasing trend from 1970 to 2014, but they are still at a medium-low levels compared with the countries and regions participating in CONCORD-3 project, suggesting that Zhongshan should continue to strengthen cancer prevention and control.

    恶性肿瘤肿瘤登记净生存率5年生存率

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    circDDX17靶向miR-223-3p/RIP3调控非小细胞肺癌细胞增殖及凋亡

    丁成智王国磊姜功前王洪涛...
    239-248页
    查看更多>>摘要：目的 探讨circDDX17通过靶向miR-223-3p/RIP3分子轴调控非小细胞肺癌细胞增殖及凋亡的分子机制。 方法 采用实时荧光定量聚合酶链反应（qRT-PCR）检测人正常肺上皮细胞株BEAS-2B和非小细胞肺癌H1299、A549、H446细胞中circDDX17、miR-223-3p、受体相互作用蛋白3（RIP3）的表达水平。分别将pcDNA、pcDNA-circDDX17、anti-miR-con、anti-miR-223-3p、pcDNA-circDDX17与miR-con、pcDNA-circDDX17与miR-223-3p mimics转染至H1299细胞。采用四甲基偶氮唑蓝法检测细胞增殖情况，流式细胞术检测细胞周期和细胞凋亡情况，平板克隆实验检测细胞增殖能力，双荧光素酶报告实验验证circDDX17与miR-223-3p、miR-223-3p与RIP3的靶向关系，Western blot法检测CyclinD1、CDK2、Cleaved caspase-3、Bax蛋白的表达水平。 结果 与BEAS-2B比较，H1299、A549、H446细胞中circDDX17 mRNA表达水平降低，miR-223-3p mRNA表达水平升高，RIP3 mRNA的表达水平降低（均P＜0.05）。pcDNA-circDDX17组细胞活力［（69.46±4.68）%］、细胞克隆数［（83.49±7.86）个］、S期细胞比例［（22.52±1.41）%］、CyclinD1、CDK2蛋白表达水平均低于pcDNA组［分别为（97.54±7.72）%、（205.03±13.37）个、（28.69±1.49）%，均P＜0.05］，pcDNA-circDDX17组细胞G0/G1期细胞比例［（64.45±3.56）%］、细胞凋亡率［（18.36±1.63）%］、Cleaved caspase-3、Bax蛋白表达水平均高于pcDNA组［分别为（51.33±2.76）%和（5.21±0.54）%，均P＜0.05］；anti-miR-223-3p组细胞活力［（72.64±5.44）%］、细胞克隆数［（78.16±8.23）个］、S期细胞比例［（21.34±1.59）%］、CyclinD1、CDK2蛋白表达水平均低于anti-miR-con组［分别为103.47±6.25、（169.32±14.53）个、（28.43±1.26）%，均P＜0.05］，anti-miR-223-3p组细胞G0/G1期细胞比例［（62.86±3.28）%］、细胞凋亡率［（14.64±1.67）%］、Cleaved caspase-3、Bax蛋白表达水平均高于anti-miR-con组［分别为（51.33±2.71）%和（4.83±0.39）%，均P＜0.05］。circDDX17与miR-223-3p存在结合位点，miR-223-3p与RIP3存在结合位点。pcDNA-circDDX17+miR-223-3p组细胞活力［（135.45±9.28）%］、细胞克隆数［（174.64±10.68）个］、S期细胞比例［（26.39±2.25）%］、CyclinD1、CDK2蛋白表达水平均高于pcDNA-circDDX17+miR-con组［分别为（101.56±6.68）%、（107.65±7.62）个、（21.64±1.72）%，均P＜0.05］，pcDNA-circDDX17+miR-223-3p组细胞G0/G1期细胞比例［（56.64±2.76）%］、细胞凋亡率［（8.34±0.76）%］、Cleaved caspase-3、Bax蛋白表达水平均低于pcDNA-circDDX17+miR-con组［分别为（64.03±3.48）%和（15.21±1.18）%，均P＜0.05］。 结论 circDDX17可靶向调控miR-223-3p/RIP3分子轴从而抑制非小细胞肺癌细胞增殖及诱导细胞凋亡。 Objective To explore the molecular mechanism of circDDX17 regulating the proliferation and apoptosis of non-small cell lung cancer cells by targeting the miR-223-3p/RIP3 molecular axis. Methods The expression levels of circDDX17, miR-223-3p, and RIP3 in human normal lung epithelial cell lines BEAS-2B and non-small cell lung cancer cells H1299, A549, and H446 were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The plasmids of pcDNA, pcDNA-circDDX17, anti-miR-con, anti-miR-223-3p, pcDNA-circDDX17 and miR-con, pcDNA-circDDX17 and miR-223-3p mimics were transfected into H1299 cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was used to detect the cell proliferation. Flow cytometry was used to detect the cell cycle and cell apoptosis. Plate cloning experiment was used to detect cell proliferation ability. The dual luciferase report experiment was applied to verify the targeting relationship between miR-223-3p with circDDX17 and RIP3. Western blot was used to detect the protein expression of cyclinD1, CDK2, cleaved caspase-3 and Bax. Results The expression levels of circDDX17 and RIP3 mRNA in H1299, A549, and H446 cells were significantly reduced (P<0.05), the expression level of miR-223-3p mRNA was significantly increased (P<0.05) compared with BEAS-2B. The cell viability [(69.46±4.68)%], the number of cell clones (83.49±7.86), the proportion of cells in S phase [(22.52±1.41) %], the protein expression levels of cyclinD1 and CDK2 in PCDNa-CircDDX17 group were lower than those in pcDNA group [(97.54±7.72)%, 205.03±13.37, (28.69±1.49)%, respectively,P<0.05], while the percentage of G0/G1 phase cells [(64.45±3.56)%], apoptosis rate [(18.36±1.63)%], the protein expression levels of cleaved caspase-3 and Bax in pcDNA-circDDX17 group were higher than those of pcDNA group [(51.33±2.76) % and (5.21±0.54) %, respectively,P<0.05]. The viability [(72.64±5.44)%], the number of cell clones (78.16±8.23), the proportion of S-stage cells [(21.34±1.59) %], the protein expression levels of CyclinD1 and CDK2 in anti-miR-223-3p group were lower than those in anti-miR-con group [(103.47±6.25)%, 169.32±14.53, (28.43±1.26)%, respectively,P<0.05]. Percentage of G0/G1 phase cells [(62.86±3.28)%], apoptosis rate [(14.64±1.67)%], the protein expression levels of cleaved caspase-3 and Bax in the anti-miR-223-3p group were higher than those of anti-miR-con group [(51.33±2.71)% and (4.83±0.39)%, respectively,P<0.05]. MiR-223-3p has complementary sites with circDDX17 or RIP3. The viability [(135.45±9.28)%], the number of cell clones (174.64±10.68), the proportion of S-phase cells [(26.39±2.25)%], the protein expression levels of cyclinD1 and CDK2 in pcDNA-circDDX17+miR-223-3p group were higher than those in pcDNA-circDDX17+miR-con group [(101.56±6.68)%, 107.65±7.62, (21.64±1.72)%,P<0.05]. Percentage of G0/G1 phase cells [(56.64±2.76)%], apoptosis rate [(8.34±0.76)%], the protein expression levels of cleaved caspase-3 and Bax in pcDNA-circDDX17+miR-223-3p group were lower than those of pcDNA-circDDX17+miR-con group [(64.03±3.48)% and (15.21±1.18)%, respectively,P<0.05]. Conclusion circDDX17 could inhibit the proliferation and induce apoptosis of non-small cell lung cancer cells via targeting the miR-223-3p / RIP3 molecular axis.

    肺肿瘤circDDX17miR-223-3p受体相互作用蛋白3增殖凋亡

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    吉西他滨长疗程维持化疗有助于中国晚期乳腺癌患者生存获益的多中心真实世界研究

    岳健宋国红李惠平孙涛...
    249-255页
    查看更多>>摘要：目的 探讨吉西他滨为主的维持治疗对晚期乳腺癌治疗疗效的影响及影响治疗持续时间的主要原因。 方法 研究为前瞻性多中心研究，2017年1月至2019年1月期间从10家医疗中心选取接受含吉西他滨单药或联合其他化疗或靶向治疗的晚期乳腺癌患者，收集吉西他滨为主方案的治疗线数、剂量、周期数、不良反应、停药原因以及疗效等数据，生存分析采用Kaplan-Meier方法，预后影响因素的单因素分析采用log rank检验，多因素分析采用Cox回归模型。 结果 研究共筛选全国10家医院共239例晚期乳腺癌患者，最终纳入224例患者进行分析。全组患者中位年龄52岁（26～77岁），其中Luminal型83例，三阴性97例，人表皮生长因子受体2阳性型44例。55.4%（124/224）为绝经后患者。完全缓解（CR）5例，部分缓解（PR）77例，疾病稳定（SD）112例，疾病进展（PD）27例。客观有效率为36.6%（82/224）。Ⅲ级及以上不良反应主要包括白细胞下降（9例）、中性粒细胞下降（49例）、血小板下降（15例）、转氨酶升高（2例）。中位随访时间41个月（26～61个月），中位无进展生存时间（PFS）为5.6个月。引起治疗结束的主要原因包括疾病进展90例、患者个人原因终止治疗51例、严重不良反应不耐受18例、医师评估后治疗结束65例。治疗周期＞6个周期较≤6个周期患者在PFS有明显的延长（8.2和5.4个月，HR=2.474，95% CI：1.730～3.538，P＜0.001）。 结论 吉西他滨为主的治疗方案在中国人群中有较好的疗效和耐受性，长程维持治疗有利于改善生存。 Objective This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients personal reasons were 51 patients adverse drug reactions were 18 patients completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

    乳腺肿瘤晚期吉西他滨治疗周期生存

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    利伐沙班预防乳腺癌导管相关血栓前瞻性队列研究中期分析

    桑蝶范善民李诗语张金涛...
    256-262页
    查看更多>>摘要：目的 探讨使用利伐沙班预防乳腺癌深静脉置管化疗患者导管相关血栓（CRT）的疗效和安全性。 方法 采取前瞻性队列研究方法，选择2020年9月至2022年3月在北京市朝阳区三环肿瘤医院接受深静脉置管化疗的乳腺癌患者，治疗组接受利伐沙班抗凝治疗，10 mg 口服1次/d，连续用药1个月；对照组未接受预防抗凝治疗。通过血管超声检查确认CRT的发生情况，组间比较采取χ2检验，CRT形成影响因素分析采用logistic回归分析。 结果 共纳入235例乳腺癌患者，置管总天数共19 035 d，平均置管天数为81 d。对照组118例，CRT发生率为28.0%（33/118）；治疗组117例，CRT发生率为20.5%（24/117），差异无统计学意义（P=0.183）。亚组分析结果显示，外周静脉穿刺中心静脉置管（PICC）165例，CRT发生率为18.2%（30/165），血栓最常见于腋静脉管周（63.3%，19/30）；锁骨下静脉置管63例，CRT发生率为39.7%（25/63），血栓最常见于锁骨下静脉管周（88.0%，22/25）；输液港7例，CRT发生率为28.6%（2/7），位于锁骨下静脉管周及颈内静脉。置管后＜30 d内形成CRT患者占54.4%（31/57），30～＜60 d形成CRT患者占22.8%（13/57），60～＜180 d形成CRT患者占22.8%（13/57）。确诊CRT患者接受利伐沙班抗凝治疗15 mg，每12 h给药1次，口服，共3个月。3个月内血栓消退率为100.0%（57/57），其中＜30 d血栓消退占71.9%（41/57），30～＜60 d为19.3%（11/57），60～＜90 d为8.8%（5/57）。单因素分析显示，锁骨下静脉置管较PICC发生CRT的风险高（P=0.001）；多因素分析显示，置管类型是血栓形成独立影响因素（OR=2.898，95%CI：1.386～6.056，P=0.005）。安全性分析显示，利伐沙班预防CRT过程中无药物相关出血、肝功能损害及骨髓抑制等不良反应。确诊CRT患者在抗凝治疗同时保留深静脉置管，输液顺畅，均按计划完成抗肿瘤治疗，未出现新发血栓和肺栓塞等异常。 结论 利伐沙班预防抗凝CRT发生比例下降，但并未达到统计学意义，需进一步增加样本量观察；利伐沙班治疗CRT疗效与安全性较好，不影响同期化疗。医务人员应针对CRT进行早预防、早发现、早治疗，改善患者的生活质量。 Objective To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies. Methods In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT. Results In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant (P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively (OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.

    乳腺肿瘤利伐沙班深静脉置管化疗导管相关血栓预防

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    直肠瘘或膀胱瘘致盆部顽固疼痛的治疗方法及疗效

    张咏梅王刚成刘英俊王有财...
    263-268页
    查看更多>>摘要：目的 探讨宫颈癌、直肠癌综合治疗（放疗、手术、化疗及其他治疗）后出现直肠瘘、膀胱瘘导致盆部顽固疼痛的治疗方法及疗效。 方法 回顾性分析2016年6月至2022年6月银川市第一人民医院和郑州大学附属肿瘤医院收治盆腔疼痛患者的临床病理资料，探讨患者综合治疗后出现盆部顽固疼痛的原因，观察临床治疗后相应的疗效。 结果 32例肿瘤患者综合治疗后出现盆部顽固性疼痛，其中宫颈癌22例，直肠癌10例。全组患者术前疼痛评分为（7.88±1.31）分。32例患者中，直肠阴道瘘或回肠阴道瘘16例，膀胱阴道瘘9例，直肠会阴瘘5例，膀胱阴道直肠瘘2例。32例患者初期给予药物止痛治疗，并根据溃破脏器行相应的近端肠管及肾盂造瘘，截留肠内容物及尿液，疼痛未明显缓解，以上方式治疗1周疼痛评分为（8.13±1.13）分，与术前相比，差异无统计学意义（P=0.417）。后期根据肿瘤是否复发、脏器是否有保留价值、手术是否受益、生存时间与提高生活质量权衡等综合评判，行病变脏器切除或修补，手术方式包括瘘口的修补、局部清创+近端肠液截留冲洗、乙状结肠远端闭合+近端造瘘术、后盆腔脏器切除、前盆腔脏器切除和全盆腔脏器切除术，术后1周患者疼痛完全缓解或消失，疼痛评分为（1.72±1.37）分，与术前、初期手术之治疗前比较差异均有统计学意义（均P＜0.001）。 结论 姑息性肾盂造瘘及近端肠管造瘘不能有效缓解盆底顽固性疼痛，缓解疼痛的根本方法为彻底阻断肠液、尿液的感染。 Objective To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments). Methods A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed. Results Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment (P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments (P＜0.001). Conclusions Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

    宫颈肿瘤直肠肿瘤直肠阴道瘘膀胱阴道瘘疼痛手术治疗放疗损伤

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