S期细胞比率对局部晚期宫颈癌新辅助化疗敏感性的预测价值

<正>宫颈癌是最常见的妇科恶性肿瘤之一。新辅助化疗(neoadjuvant chemotherapy,NACT)是综合治疗局部晚期宫颈癌方案中的一项重要治疗策略[1],但目前临床尚无统一判断化疗疗效的标准。本实验采用流式细胞术分析局部晚期宫颈癌新辅助化疗前后     

中国大陆部分地区局部晚期宫颈癌治疗状况调查及分析

目的通过中国宫颈癌多中心临床诊疗大数据,探讨我国局部晚期宫颈癌的治疗现状。方法从中国大陆部分地区34家三级甲等医院收集的2004—2016年共30 665例宫颈癌临床诊疗数据中调取局部晚期宫颈癌(ⅠB2期和ⅡA2期)患者4420例,回顾性分析近13年来局部晚期宫颈癌治疗现状。结果 (1)手术治疗者3908例(88.4%),年龄(45.73±8.53)岁;根治性放化疗者312例(7.1%),年龄(50.56±9.90)岁;70例(1.6%)患者未行治疗,130例(2.9%)患者治疗情况不详。(2)4420例局部晚期宫颈癌中3908例患者选择手术治疗,其中有2315例(59.2%)患者采用术前辅助治疗后再行手术治疗,1593例(40.8%)采取直接手术治疗方式;2004—2016年间,辅助治疗后手术者与直接手术者例数均随时间呈先升高-再下降趋势,但是辅助治疗后手术者升高的曲率高于直接手术者;根据术前辅助治疗方式和途径的不同,选择新辅助静脉化疗者1692例(73.1%),其应用率随时间呈逐年升高趋势,其余术前辅助治疗方式应用率均随时间呈逐年下降趋势。(3)312例行根治性放化疗的局部晚期宫颈癌患者,根治性放化疗联合方案有多种,根据化疗功效和时机分为新辅助化疗+根治性放疗方案130例(41.7%),新辅助化疗+同步放化疗方案77例(24.7%),根治性放疗方案43例(13.8%),同步放化疗方案16例(5.1%),同步放化疗+辅助化疗组31例(占9.9%),根治性放疗+辅助化疗方案15例(4.8%)。结论在中国近13年来,局部晚期宫颈癌患者选择手术治疗的患者明显多于选择根治性放化疗的患者。目前我国根治性放化疗方案多样,以先行诱导化疗后再行根治性放疗或根治性同步放化疗的方案最多见。     

子宫颈癌同步放化疗的相关问题

化疗加放疗治疗宫颈癌已有多年历史。20世纪70年代采用放疗前行化疗，称之为新辅助化疗，以后经过多年实践表明，放疗前或放疗后给予化疗不能提高宫颈癌患者的生存率；至80年代初开始尝试采用同步放化疗治疗宫颈癌。1999-2000年，美国新英格兰医学杂志及临床肿瘤杂志相继发表5个大样本随机对照临床研究，结果表明，同步放化疗提高了宫颈癌患者（包括Ⅰb、Ⅱa期根治性手术后具有高危因素者）的生存率和局部控制率，减少了死亡的危险。[第一段]     

新辅助化疗在宫颈癌治疗中的应用现状及争议

宫颈癌是全球妇女发病率仅次于乳腺癌的恶性肿瘤[1],严重威胁女性的健康。传统治疗手段并未明显改善宫颈癌患者的总5年生存率,故新辅助化疗（neoadjuvant chemotherapy,NACT）备受关注[2],其主要应用于局部晚期宫颈癌（locally advanced cervical cancer,LACC）的治疗。     

局部晚期宫颈癌放射治疗

宫颈癌在发展中国家发病率仍较高,其中接近80%患者诊断为局部晚期宫颈癌（LACC）。美国国立综合癌症网络（NCCN）Ⅰ类推荐LACC患者治疗为盆腔放射治疗+腔内后装治疗+顺铂为基础同步化疗,目前LACC患者5年生存率仍徘徊在70%左右。文章结合相关文献,简述LACC患者放射治疗基本方法、原则及疗效,同时就提高放疗效果措施及进展,包括精准放疗、同步化疗、新辅助化疗、放疗后巩固化疗、手术病理分期及联合靶向治疗相关临床应用及研究展开综述及讨论。     

同步放化疗与新辅助化疗术前用药在局部中晚期宫颈癌治疗中的临床疗效评价

目的:比较同步放化疗与新辅助化疗术前用药在治疗局部中晚期宫颈癌的临床疗效。方法:选择2002年3月至2005年3月我院收治的42例ⅠB2～ⅡB期宫颈癌患者,其中21例同步放化疗,21例新辅助化疗。两组化疗方案相同,鳞癌:顺铂(DDP)+博来霉素;腺癌:DDP+5-氟尿嘧啶(5-Fu)+丝裂霉素(MMC)。同步放化疗组化疗期间配合放疗,采用腔内近距离放疗。同步放化疗、新辅助化疗结束后选择合适时间手术。观察两组间的近期疗效、手术率及手术切缘阴性情况、毒副反应、远期疗效(1、3、5年生存率)。结果:两组间近期疗效差异无统计学意义(P>0.05)、手术率及手术切缘阴性率差异有高度统计学意义(P<0.01)。血液和胃肠道毒副反应差异无统计学意义(P>0.05),晚期并发症放射性直肠炎和膀胱炎差异有高度统计学意义(P<0.01)。1年、3年生存率差异无统计学意义(P>0.05),而5年生存率同步放化疗组高于新辅助化疗组(P<0.05)。结论:同步放化疗术前用药治疗局部中晚期宫颈癌优于新辅助化疗。     

子宫颈癌新辅助化疗影响因素与药物敏感性基因

新辅助化疗（neoadjuvant chemotherapy,NACT）是局部晚期宫颈癌的综合治疗方式之一,部分相关化疗药物敏感性基因对肿瘤耐药、化疗副反应的预测作用取得了进展。宫颈癌肿瘤大小是影响新辅助化疗近期疗效的独立因素;核苷酸切除修复交叉互补组1（ERCC1）、Ⅲ微管蛋白（TUBB3）、核糖核苷酸还原酶M1（RRM1）基因阳性或过度表达可作为铂类、抗微管类和吉西他滨药物耐药的预测标志,但不推荐临床常规检测及应用,尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）多态性与伊立替康毒副反应有关,为预测宫颈癌新辅助化疗近期疗效及个体化治疗提供参考。     

单纯放疗、新辅助化疗及同步放化疗治疗宫颈癌临床近期疗效比较

目的探讨单纯放疗、新辅助化疗、同步放化疗三种非手术疗法治疗宫颈癌的疗效。方法收集2004-2009年在中国医科大学附属第一医院妇科和放疗科诊治的宫颈癌患者120例,分为两组。(1)术前治疗组:Ⅰb～Ⅱa期患者60例,包括单纯放疗组(20例)、新辅助化疗组(20例)、同步放化疗组(20例)。(2)非手术治疗组:Ⅱb～Ⅲb期患者60例,包括单纯放疗组30例,同步放化疗组30例。进行临床疗效和临床病理资料的分析对比研究。结果术前同步放化疗组和新辅助化疗组近期有效率分别为90%和85%,显著高于术前单纯放疗组(55%)(P0.05);术后病理淋巴结转移率单纯放疗组(50%)高于同步放化疗组(30%)和新辅助化疗组(10%)(P0.05);宫旁转移率三者比较差异无统计学意义。术前单纯放疗组低分化者肿瘤缩小率(95.7%)显著高于高中分化者(59.4%),新辅助化疗组高中分化者肿瘤缩小率(87.1%)显著高于低分化者(50.3%)。非手术治疗组中同步放化疗组肿瘤平均缩小率(72.6%)显著高于单纯放疗组(37.7%)(P0.05)。结论 (1)术前同步放化疗与新辅助化疗可使肿瘤体积在短时间内缩小明显,利于手术治疗,并能降低淋巴结转移率。(2)低分化宫颈癌对放疗敏感,高中分化宫颈癌对化疗敏感。(3)中晚期宫颈癌治疗中同步放化疗较单纯放疗更有效。     

宫颈癌新辅助化疗与同步放化疗

宫颈癌的治疗采用以手术、放疗为主的综合治疗。化疗在宫颈癌的治疗过程中作用日渐重要,应用广泛,但在临床具体应用过程中还存在一些问题,该文介绍了宫颈癌的新辅助化疗及同步放化疗的研究现状。     

宫颈癌新辅助化疗临床研究现状

新辅助化疗是指在局部治疗（手术或放疗）前给予的全身化疗。近二十余年来国内外学者对宫颈癌新辅助化疗联合手术或放疗的治疗模式进行了一些探索,取得一定经验。但新辅助化疗在宫颈癌治疗中的地位仍未明确,且对其化疗方案选择目前无统一认识。对新辅助化疗在宫颈癌治疗方面的最新进展、多种新辅助化疗方案应用于宫颈癌的疗效及其发展趋势做综述。     

局部晚期宫颈癌术前化疗药物及方案的选择

局部晚期宫颈癌的治疗目前有很大的争议,美国国立综合癌症网络（NCCN）指南推荐直接行放疗,但其技术问题可能会引起不可逆的相关并发症,损伤性较大,而新辅助化疗+宫颈癌手术,是目前很多国家及地区采用的治疗方案,但目前没有统一的化疗方案、用药剂量以及强度,如何筛选出对新辅助化疗不敏感的患者以制定更加合理的治疗方案,避免治疗时机的贻误,尚需大样本、随机、多中心研究结果的支持。文章就宫颈癌新辅助化疗相关问题做一综述,旨在为临床治疗提供理论基础。     

Neoadjuvant chemotherapy in cervical cancer: a 67 patients experience

The purpose of this study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy in patients with locally advanced cervical cancer. Between 1992 and 2003, all consecutive women with locally advanced cervical cancer receiving neoadjuvant chemotherapy were identified. Sixty-seven patients received neoadjuvant chemotherapy: 34 had stage I disease, 28 had stage II disease, and 5 had stage III disease. Clinical response to neoadjuvant chemotherapy occurred in 61 patients, including six with complete and 55 with partial response; five women showed stable disease and one progressed. After neoadjuvant chemotherapy, 58 women underwent surgery, whereas the remaining nine received radiation. Hematologic toxicity was seen in 14 patients, with most of them consisting in severe anemia. The 5-year survival rate and median survival were 63% and 93 months. In univariate analysis, response to neoadjuvant chemotherapy, treatment after neoadjuvant chemotherapy, cervical stromal invasion >50%, and lymph node involvement were important prognostic factor responsible for survival. Neoadjuvant chemotherapy followed by surgery seems to be tolerated and active in the treatment of locally advanced cervical cancer and might be an alternative choice of therapy to chemoradiation. A prospective randomized trial with a larger number of cases is needed.     

子宫颈癌术前辅助治疗的规范化

新辅助化疗(neoadjuvant chemotherapy,NACT)是子宫颈.癌术前或放疗前辅助治疗的主要方式,原则上适用于局部晚期(Ⅰ B3～ⅣA期)和部分特殊类型的子宫颈癌患者.顺铂为首选药物,推荐化疗2～3个疗程.肿瘤直径大于4cm的Ⅰ B3～ⅡA2期的子宫颈鳞癌和腺癌的部分患者可以采用新辅助化疗+根治性手术...     

新辅助化疗在宫颈癌治疗中的作用

新辅助化疗的概念于1983年首次提出。目前新辅助化疗在宫颈癌治疗方面虽仍有争议,但随着医疗技术的不断发展其作用优势逐步显现。新辅助化疗不但可以缩小肿瘤体积、提高手术切除率,而且可延长妊娠期宫颈癌患者的妊娠时间,使其获得存活新生儿。故新辅助化疗的出现为局部晚期宫颈癌患者、晚期宫颈癌患者和妊娠期宫颈癌患者的治疗提供了新的思路。综述新辅助化疗概念的提出、所存争议、作用机制及其在宫颈癌综合治疗中的作用。     

局部晚期宫颈癌术前新辅助化疗的益处

局部晚期宫颈癌的标准治疗方案目前仍存在争议,而新辅助化疗在局部晚期宫颈癌中的应用并没有在世界范围内达成共识,其临床治疗效果也不确定。多项临床试验表明术前新辅助化疗在局部晚期宫颈癌的治疗中发挥着重要作用,但我们必须明确该治疗方案的适应证和禁忌证,实施前充分考虑其利弊。术前新辅助化疗治疗局部晚期宫颈癌的疗效还有待进一步验证。     

Neoadjuvant chemotherapy: an alternative option of treatment for locally advanced cervical cancer

Although the incidence of cervical cancer has declined in both North America and Europe, it still represents the second most common cancer in women and the fifth most common malignancy worldwide. Most patients in the developed countries present with disease either confined to the cervix or with limited extension beyond it. Historically, the standard treatment was usually radiotherapy or radical hysterectomy with node dissection. In 1999, five randomized clinical trials performed by the Gynecologic Oncology Group, the Radiation Therapy Oncology Group and the Southwest Oncology Group have demonstrated a significant outcome advantage when cisplatin-based chemotherapy was administered during radiation in patients with cervical cancer. In the current review, we will analyze the role of neoadjuvant chemotherapy followed by radiotherapy and surgery as an alternative option treatment to the standard chemoradiation for locally advanced cervical cancer (stage Ib2 or larger).     

增殖细胞核抗原对局部晚期宫颈癌新辅助化疗敏感性的预测价值

目的探讨增殖细胞核抗原作为评价局部晚期宫颈癌新辅助化疗敏感性指标的可行性。方法收集2007年1月至2007年9月南华大学第一附属医院妇产科收治的49例局部晚期宫颈癌患者新辅助化疗前后标本组织,采用免疫组织化学技术检测癌组织中增殖细胞核抗原的表达。结果49例局部晚期宫颈癌患者经新辅助化疗治疗2周后评价临床疗效,临床有效(CR+PR)率为79.6%(39/49)。新辅助化疗有效组化疗前宫颈癌组织中PCNA阳性细胞数比率明显高于无效组(P0.05)。结论增殖细胞核抗原(PCNA)是判定局部晚期宫颈癌化疗敏感性的重要指标。     

The integration of chemotherapy into the management of locally advanced cervical cancer: a pilot study

Chemotherapy has been traditionally reserved as a last-time treatment for cervical cancer patients and in this setting long-term remissions are unusual. Platinum-based combination chemotherapy has been associated with high tumor response rates in patients with advanced and metastatic cervical tumors and past experience encouraged evaluation of chemotherapy as a first-line treatment in patients with locally advanced tumors where there is a high likelihood of relapse with local treatment. Thirty patients were treated initially with three courses of cis-platinum, vinblastine, and bleomycin with an overall response rate of 67%, and then had either radiotherapy or surgical resection. The initial results have been encouraging and the integration of chemotherapy into the management of locally advanced cervical cancer warrants further investigation.     

Recent advances and problems in primary therapy for cervical cancer in Taiwan.

Cervical cancer is a serious health problem in Taiwan, with nearly 2700 women developing the disease each year. The estimated incidence of this disease from 1993 to 1997 was 21.8 per 100,000 woman-years. The lack of effective Papanicolaou smear screening systems was the major cause of the high prevalence rate before 1995. Surgery and radiotherapy are the standard treatments for early stage cervical cancer. For women with advanced stage cervical cancer, external-beam pelvic radiation followed by intracavitary radiotherapy is the treatment of choice. Although randomized clinical trials have shown that concurrent chemoradiotherapy should be regarded as the standard treatment for locally advanced cervical cancer (stage IIB to IVA), the impact of the complications associated with this treatment have not been evaluated in Taiwanese studies. Localized bulky (stage IB2 or bulky IIA) tumors are commonly treated with various combinations of chemotherapy, surgery and radiotherapy, despite unresolved concerns about the morbidity and effectiveness of this approach compared with definitive radiotherapy or radical surgery. Although about 60% of Taiwanese women with cervical cancer receive primary surgical treatment, about 20% do not receive treatment or receive non-standard therapies. Efforts are needed to increase the screening rate, to improve access to medical care, and to provide public education for patients to reduce the occurrence and mortality of cervical cancer in Taiwan.