局部晚期子宫颈癌新辅助化疗疗效分析

目的 探讨Ⅰb2~Ⅱb期子宫颈癌新辅助化疗的疗效.方法 回顾性分析手术治疗的84例Ⅰb2~Ⅱb期子宫颈癌患者的病历资料,患者术前均行1~3次静脉或动脉化疗,通过比较和分析化疗前后病灶进展情况、血清鳞状细胞癌抗原(SCC-Ag)值以及术后的总生存率和3年无病生存率,进而评价新辅助化疗的疗效.结果 84例患者化疗有效率为82.1%,完全缓解5例,部分缓解64例,病情稳定13例,疾病进展2例;化疗效果与临床分期、病理类型、肿瘤大小均无关(P﹥0.05);新辅助化疗后患者SCC-Ag水平明显下降(P﹤0.001);随访患者3年总生存率及无病生存率均为93%.结论 子宫颈癌新辅助化疗安全有效,可以有效缩小病灶,提高患者的预后,具有重要的临床意义.     

Neoadjuvant chemotherapy in cervical cancer: an update

The role of neoadjuvant chemotherapy (NACT) has been investigated in order to improve prognosis of patients with locally advanced cervical cancer. According to a meta-analysis, NACT followed by radiotherapy may be detrimental with a low dose of cisplatin and longer cycle intervals. Some meta-analyses showed NACT followed by surgery resulted in a reduction in the risk of death by 35% with a gain of 14% in the 5-year survival compared with radiotherapy. In a Cochrane meta-analysis, overall survival and progression-free survival were significantly improved with NACT followed by surgery versus surgery alone (23% reduction in the risk of death). The platinum/paclitaxel combination is now the preferred regimen in the neoadjuvant setting and preliminary data indicate that dose-dense regimens are feasible and effective (overall response rate: 67.8–87%). A weekly regimen with carboplatin/paclitaxel before chemoradiation showed promising results and the INTERLACE ongoing trial will help to confirm whether additional short-course chemotherapy given weekly before chemoradiation will lead to an improvement in overall survival.     

Neoadjuvant chemotherapy with cisplatin, ifosfamide and paclitaxel for locally advanced squamous-cell cervical cancer

Background: Neoadjuvant chemotherapy is increasingly being used for the treatment of bulky and locally-advanced cervical cancer. Cisplatin and ifosfamide are known to be effective in cervical cancer, while paclitaxel is one of the promising new drugs for the treatment of this neoplasm.Objective: To assess the toxic effects and antitumor activity of a multidrug neoadjuvant regimen consisting of cisplatin, ifosfamide, and paclitaxel in bulky and locally advanced cervical cancer.Patients and methods: Thirty-eight patients with pathology-confirmed squamous-cell cervical cancer (27 IB2-IIA, two IIB, eight IIIB, one IVA) were prospectively enrolled in the study. Their treatment consisted of paclitaxel 175 mg/m² given over three hours on day 1, cisplatin 50 mg/m² (75 mg/m² in 10 patients), ifosfamide 5 g/m² in a 24-hour continuous infusion and mesna 5 g/m² in a 24-hour continuous infusion on day 2, and mesna 3 g/m² in a 24-hour continuous infusion on day 3. The course was repeated every three weeks for three courses and all of the patients, except those with disease progression or who were inoperable, were scheduled for radical hysterectomy and pelvic lymphadenectomy.Results: All patients are evaluable for response. Eleven achieved clinical complete responses, 21 had partial responses, five had stable disease and one had progression of disease. Of 34 patients who underwent surgery, six (16%) had pathology-documented complete responses, seven (18%) had partial responses with only microscopic residual disease in the cervix, 19 had sub-optimal partial responses, and two had stable disease, for an overall response rate of 84% (95% confidence intervals (CI): 68.7%–94%).Grade 3–4 neutropenia was recorded for 27 (71%) patients, grade 3–4 thrombocytopenia for four (10.5%), and grade 2 peripheral neuropathy for two (2.5%).At a median follow-up of 16 months (range 7–22), 29 (76%) women are alive without recurrence, seven are alive with persistent/recurrent disease and two have died of their disease.Conclusions: According to pathology examination, this regimen yields a 34% complete and optimal partial response rate with acceptable toxicity, and it should be prospectively compared to other regimens.     

新辅助化疗治疗巨块型宫颈癌的疗效

目的：观察新辅助化疗对巨块型宫颈癌的临床治疗效果.方法：收集我院收治的巨块型宫颈癌患者55例,“PF96h”方案（顺铂75mg/m2,氟尿嘧啶4000mg/m2连续泵入96h）对其进行新辅助化疗.通过肉眼观察、血管造影及病理检查观察其临床疗效.结果：新辅助化疗后肿块直径较化疗前出现了不同程度的缩小,统计学差异明显（P＜0.05）.总有效率80％,其中Ⅰb期疗效达88％,宫颈癌临床分期越晚,新辅助化疗的有效率逐渐下降,但Ⅱb-Ⅳa期有效率仍可达50％以上.不同期宫颈癌患者化疗后局部血流均明显减少.术后大体标本切缘病理切片均未见癌细胞.结论：新辅助化疗能明显降低巨块型宫颈癌的直径,增加手术机会,提高手术几率,为根治手术创造条件.     

Neoadjuvant chemotherapy followed by radiotherapy and concurrent hyperthermia in patients with advanced-stage cervical cancer: A retrospective study

Objective: To evaluate the efficacy of neoadjuvant chemotherapy, followed by radiotherapy and concurrent hyperthermia (triple therapy) in patients with advanced-stage cervical cancer.

Methods: We selected 43 patients from our hyperthermia database, who were treated from 1996 to 2010 with triple therapy for large primary tumours (>6?cm) or para-aortic lymph node metastases. All patients received platinum-based chemotherapy followed by full-dose radiotherapy, brachytherapy and five hyperthermia treatments. The response was evaluated by gynaecological examination and a CT-scan. Time-to-event variables were estimated using the Kaplan Meier method and the Cox regression method.

Results: The mean age of the patients was 50.4 years (range 29–80). The median tumour size was 5.6?cm at diagnosis (range 2.6–8.2), positive lymph nodes were present in 90.7%. A total of 67% of the patients completed all six planned courses of chemotherapy. After completion of neoadjuvant chemotherapy, 83.7% of patients achieved a complete or partial response. At the end of treatment, the complete response rate was 81.4% (95%CI 69.2–93.5). Grade 2, 3 and 4 acute vascular toxicity occurred in 17 patients. The incidence of grade 3–4 haematological toxicity did not exceed 10% and no neutropenic fever occurred. For grade 1–2 renal toxicity, a switch to carboplatin was made (n?=?6). No acute grade 3–4 renal toxicity was observed. No treatment-related deaths were recorded. The median follow-up time was 29.8 months (range 4.1–124.8). Overall survival rate at 12 months was 79% (95%CI 57.4–92.3).

Conclusion: The triple therapy seems feasible and effective in the treatment of advanced-stage, high-risk cervical cancer. However, chemotherapy-induced vascular toxicity occurred frequently, which may warrant the use of prophylactic anticoagulants. We recommend a phase II trial for prospective confirmation for comparison with standard chemoradiation and the use of anticoagulants.     

白蛋白结合型紫杉醇新辅助化疗对宫颈癌患者术后疗效影响的研究

目的 探究白蛋白结合型紫杉醇新辅助化疗对宫颈癌患者术后疗效的影响.方法 选取宫颈癌患者104例,根据治疗方法不同将患者分为治疗组与对照组,每组各52例.对照组患者接受顺铂联合紫杉醇新辅助化疗治疗;治疗组患者接受顺铂联合白蛋白结合型紫杉醇新辅助化疗治疗.结果 治疗前,两组患者的瘤体最大直径比较,差异无统计学意义(P﹥0.05);治疗后,治疗组患者的瘤体最大直径明显小于对照组(P﹤0.01).治疗组患者的术中出血量明显少于对照组(P﹤0.01),单次给药时间、手术时间明显短于对照组(P﹤0.01).治疗过程中,治疗组患者的荨麻疹及低血压发生率均低于对照组(P﹤0.05);两组患者周围感觉神经病变及肾功能异常发生率比较,差异无统计学意义(P﹥0.05).治疗组患者化疗总有效率高于对照组(P﹤0.05);治疗组患者的术后1年复发率低于对照组(P﹤0.05).结论 白蛋白结合型紫杉醇相对普通紫杉醇具有不良反应轻,疗效明显,患者耐受性好等优势.     

SCC-Ag与宫颈癌新辅助化疗患者预后的相关性

目的:探索化疗前、后鳞状细胞癌抗原(SCC-Ag)及其变化对宫颈癌新辅助化疗患者预后的预测价值.方法:收集191例宫颈癌患者的临床资料,分析其预后情况与临床特征间的关系,探讨不同阶段SCC-Ag对预后的评估意义.结果:化疗反应、淋巴结转移及FIGO分期与预后呈现出一定的相关性(P<0.05),而年龄、绝经情况和组织分型与预后无关;化疗前SCC-Ag<2.8 ng/ml组5年生存率为89.47%,SCC-Ag≥2.8 ng/ml组为79.17%(P=0.048 4);化疗后SCC-Ag<0.9 ng/ml组5年生存率为90.32%,SCC-Ag≥0.9 ng/ml组为78.57%(P=0.023 8);SCC-Ag下降程度≥50%和<50%之间比较差异无统计学意义.结论:化疗前和化疗后的SCC-Ag水平对宫颈癌新辅助化疗患者预后有一定的评估价值.     

A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer

Background:

We investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT) with paclitaxel and carboplatin before radical chemoradiation (CRT) and assessed the response rate to such a regimen.

Methods:

CxII is a single-arm phase II trial of 46 patients, with locally advanced cervical cancer (stage Ib2-IVa). Patients received dose-dense carboplatin (AUC2) and paclitaxel (80 mg m⁻²) weekly for six cycles followed by CRT (40 mg m⁻² of weekly cisplatin, 50.4 Gy, 28 fractions plus brachytherapy). The primary end point was response rate 12 weeks post-CRT.

Results:

Baseline characteristics were: median age at diagnosis 43 years; 72% squamous, 22% adenocarcinoma and 7% adenosquamous histologies; FIGO stage IB2 (11%), II (50%), III (33%), IV (7%). Complete or partial response rate was 70% (95% CI: 54–82) post-NACT and 85% (95% CI: 71–94) post-CRT. The median follow-up was 39.1 months. Overall and progression-free survivals at 3 years were 67% (95% CI: 51–79) and 68% (95% CI: 51–79), respectively. Grade 3/4 toxicities were 20% during NACT (11% haematological, 9% non-haematological) and 52% during CRT (haematological: 41%, non-haematological: 22%).

Conclusion:

A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT. This treatment regimen is feasible as evidenced by the acceptable toxicity of NACT and by the high compliance to radiotherapy (98%).     

PRMT1 expression predicts response to neoadjuvant chemotherapy for locally advanced uterine cervical cancer

The standard care for patients with locally advanced cervical cancer is concurrent chemoradiotherapy. Successful neoadjuvant chemotherapy (NAC) can reduce tumor size and enable patients to be eligible for a hysterectomy, which can improve their prognosis. Selecting the right candidate for NAC is important since NAC failure results in switching to radiation therapy and can lead to a worse prognosis due to a delay in the initiation of the core therapy. Therefore, the identification of biomarkers that can predict the effect of NAC is essential. Previous reports have suggested a relationship between protein arginine methyltransferase (PRMT1) and chemoresistance in several types of cancer. PRMT1 has been demonstrated to methylate apoptosis signal-regulated kinase 1 and to inhibit its activity, thereby contributing to chemoresistance. The present study investigated the association between PRMT1 expression and the efficacy of NAC in locally advanced cervical cancer. Data from 53 patients with locally advanced uterine cervical cancer who were classified into two groups based on effective (n=28) and ineffective (n=25) responses to NAC treatment were evaluated. PRMT1 expression was investigated by immunohistochemistry and scored using a weighted scoring system. Additionally, the present study investigated the effect of RNA interference-mediated downregulation of PRMT1 on the sensitivity of cervical cancer cells to cisplatin in vitro. The results demonstrated that the NAC effective group had significantly lower weighted PRMT1 scores than the NAC ineffective group (P=0.030). In addition, lower tumor expression levels of PRMT1 were significantly associated with increased sensitivity to NAC (P=0.033). Furthermore, downregulation of PRMT1 expression in cervical cancer cells markedly improved their sensitivity to cisplatin in vitro. The present study suggested that PRMT1 expression has potential as a predictive marker of the efficacy of NAC in patients with locally advanced cervical cancer. This finding can contribute to improvements in the prognosis of these patients.     

宫颈癌组织AKT和P-AKT表达与LMVD相关性及其对新辅助化疗效果预测意义

目的 宫颈癌新辅助化疗(neoadjuvant chemotherapy,NACT)的疗效一直存在争议,PI3K/AKT通路在肿瘤细胞增殖、迁移、侵袭及抗凋亡都起到举足轻重的作用.本研究探讨NACT对宫颈鳞状细胞癌AKT通路中AKT及P-AKT的表达对肿瘤微淋巴管生成的影响,并分析其变化与NACT临床疗效的关系.方法 采用免疫组化SP法分别检测2011-03-01-2016-03-31滨州医学院附属医院收治的47例 ⅠB2~ⅡB期宫颈鳞癌患者行NACT前后AKT和P-AKT的表达情况及肿瘤微淋巴管密度(lymphatic microvessel density,LMvD)的变化.结果 免疫组化检测结果显示,NACT前AK和P-AKT的阳性率分别为93.6%和72.3%,化疗后阳性率分别为44.7%和36.2%,NACT前后比较,AKT和P-AKT表达差异有统计学意义,P<0.001.化疗前宫颈鳞癌组织中LMvD计数为20.87±3.31,化疗后宫颈鳞癌组织中LMvD计数为16.47±3.44,化疗后宫颈鳞癌组织中LMvD明显降低,t=6.32,P<0.001.化疗前宫颈鳞癌AKT阳性的LMvD为21.14±3.19,高于阴性组(17.00±3.00).Spearman相关分析显示,化疗前后LMvD的表达(rs=0.39,P=0.007)与化疗前后P-AKT的表达(rs=0.66,P<0.001)均呈正相关.化疗后LMvD与化疗后AKT的表达呈正相关,rs=0.58,P<0.001.淋巴结转移与化疗前后LMvD均呈正相关(rs=0.44,P<0.001;rs=0.36,P=0.013).淋巴结转移的患者化疗前化疗后LMvD均高于淋巴结未转移者.结论 化疗前P-AKT的表达及化疗后AKT和P-AKT的表达与肿瘤微淋巴管生成呈正相关,LMvD与淋巴结的转移呈正相关,化疗前P-AKT的表达有可能作为预测宫颈癌新辅助化疗疗效的指标.     

Survivin 和 MRP1 在宫颈鳞癌中的表达及其对新辅助化疗敏感性的预测研究

目的：探讨新辅助化疗前后Survivin、MRPl在宫颈鳞癌组织中的表达及其与化疗敏感性的关系。方法：采用免疫组化sP法对38例宫颈鳞癌患者新辅助化疗（NACT）前后MRPl、Survivin的表达水平进行检测。结果：NACT前Survivin的阳性表达率（63．16％）显著高于NACT后（39．47％）（P〈0．05）,且NACT前Sur—vivin表达阴性者化疗有效率（92．86％）高于表达阳性者（62．50％）（P〈0．05）。Survivin的表达水平与宫颈鳞癌的分化程度相关（P〈0．05）,但与年龄、临床分期不相关（P〉0．05）。新辅助化疗前后MRPl在宫颈鳞癌中的阳性表达率分别为84．21％和92．11％,两者间无显著性差异（P〉0．05）,且化疗前MRPl表达阴性者与表达阳性者化疗有效率分别为83．33％、71．88％,两者问无显著性差异（P〉0．05）。MRPl的表达与宫颈癌的临床分期、分化程度、年龄均不相关（P〉0．05）。结论：Survivin、MRPl在宫颈鳞癌组织中均有较高的表达水平,但只有Survivin的表达水平与NACT疗效具有显著的相关性,Survivin的表达水平可作为预测宫颈鳞癌对化疗敏感性的指标。     

宫颈癌新辅助化疗的现状与争议宫颈癌新辅助化疗的现状与争议

针对新辅助化疗研究的现状及存在的问题,通过查找几年来关于宫颈癌新辅助化疗的相关文献显示,宫颈癌发病率逐年呈上升趋势。其治疗手段目前仍以手术、放疗、化疗为主,治疗效果并无明显提高,尤其中晚期或复发的患者5年生存率更低。新的化疗药物的研究对宫颈癌治疗有一定疗效,宫颈癌的化学治疗越来越受到国内外学者的重视。新辅助化疗(neoadjuvant chemotherapy,NACT)的出现在很大程度上改善了患者的预后,提高了患者存活率。     

新辅助顺铂联合化疗在宫颈鳞癌治疗中的作用

目的评价顺铂联合化疗在宫颈鳞癌治疗中的作用.方法将54例Ⅰ B2～ⅡB期宫颈鳞癌随机分为2组,26例采用新辅助化疗后手术,28例直接手术,评价术前化疗的疗效,比较两组的2年及5年生存率和平均生存时间.结果新辅助化疗后宫颈局部病灶缩小和宫旁改善总有效率为84.6%(22/26).新辅助化疗组与未化疗组的2年生存率分别为80.8%(21/26)和82.1%(23/28)(P》0.9),5年生存率分别为73.1%(19/26)和57.1%(16/28),无显著性差异(P《0.25).两组的平均生存时间分别为59.3个月和48.8个月(P《0.05);化疗组中ⅠB2～ⅡA期平均生存时间为65.4个月,与非化疗组49.8个月相比提高15.6个月,有显著性差异(P《0.05).两组病例手术的术中出血、手术时间、术后尿管留置时间均无显著差异.结论新辅助化疗能有效控制宫颈病灶,改善宫颈鳞癌患者的预后.     

TP与PF方案在宫颈癌新辅助化疗中的对比研究

目的：对比观察紫杉醇联合顺铂（TP）与氟尿嘧啶联合顺铂（PF）在宫颈癌新辅助化疗中的疗效和毒副作用。方法：66例Ⅰb2-Ⅱb期宫颈癌患者,随机分为两组,A组（32例）行PF方案化疗两周期、B组（34例）行TP方案两周期,比较两组疗效及毒副作用。结果：A、B两组两周期化疗后有效率分别达43.33%和65.63%,完全缓解率分别为6.67%（2/30）和12.50%（4/32）,B组有效率明显高于A组,统计学比较差异有显著性。两组毒副作用相当。结论：紫杉醇联合顺铂是宫颈癌较为理想的新辅助化疗方案。     

宫颈癌新辅助化疗前后 SCC －Ag 水平与化疗敏感性的关系

目的：探究化疗前,化疗后 SCC －Ag 对宫颈癌新辅助化疗（NACT）敏感性的预测价值。方法：收集262例宫颈鳞癌患者的完整信息,研究 SCC －Ag 与各临床特征的关系,并分析影响宫颈癌 NACT 敏感性的因素,重点探讨不同阶段 SCC －Ag 对化疗敏感性的评估作用。结果：宫颈鳞癌患者 NACT 前 SCC －Ag 水平与年龄、绝经情况及组织分型无关（P ＞0．05）,与肿瘤直径、FIGO 分期和淋巴结转移呈正相关。NACT 有效率为71．0％（186／262）,影响其敏感性的因素有肿瘤直径和 FIGO 分期。按 NACT 后 SCC －Ag 下降的百分比分为＜0．40、[0．40,0．70）、≥0．70三组,各组所对应的肿瘤直径的变化分别为（6．18±10．07）mm、（21．30±11．93）mm、（28．47±14．27）mm,而这三组所对应的化疗反应率分别为14．52％、80．46％、94．69％,以上结果均具有统计学意义（P ＜0．05）。结论：化疗后下降的 SCC －Ag 对宫颈癌 NACT 敏感性具有很好的评估价值。     

新辅助化疗联合宫颈癌根治术治疗局部晚期宫颈癌的疗效及安全性分析

目的:研究多西他赛+奈达铂的新辅助化疗联合宫颈癌根治术治疗局部晚期宫颈癌的疗效及安全性。方法:收集自2014年1月至2019年10月就诊于陕西省肿瘤医院的248例局部晚期宫颈癌患者的临床资料进行回顾性分析,接受新辅助化疗联合宫颈癌根治术治疗的患者为观察组,只接受宫颈癌根治术的患者为对照组,每组124例。结果:两组患者年龄、体质量指数（BMI）、临床分期、病理分型、初治时肿瘤直径等一般临床资料比较,差异无统计学意义（P＞0.05）,两组具有可比性。平均新辅助化疗次数1.30次,新辅助化疗后肿瘤的体积明显缩小。观察组手术时间更短、术中出血量更少并且手术并发症发生率也降低（P＜0.05）,淋巴结清扫数量、阴道切除长度均无统计学差异（P＞0.05）。术后两组平均化疗次数及化疗不良反应发生率相比未见统计学差异（P＞0.05）。结论:多西他赛+奈达铂的新辅助化疗能够显著缩小宫颈肿瘤体积、降低手术难度、缩短手术时间、减少术中出血量、减低手术并发症发生率,而且在提高临床疗效的同时不增加不良反应发生率。     

宫颈癌的新辅助时辰化疗

目的　观察以时辰给药法进行新辅助化疗与常规新辅助化疗治疗宫颈癌的近期疗效及毒副作用。方法　时辰新辅助化疗组用药为顺铂 (DDP) ,给药时间为 4pm ;氟脲嘧啶 (5 -Fu) ,给药时间为 0am～ 8am ,在3am～ 5am给予药物总量的 75 %。常规新辅助化疗组所用药物及剂量同时辰新辅助化疗组 ,用药时间安排在正常上班时间的 8am～ 5pm。完成 2个疗程化疗后根据患者检查情况选择手术治疗或根治性放疗 ,评价化疗近期的毒副反应及化疗的近期疗效。结果　时辰新辅助化疗组总有效率与常规新辅助化疗组相比为88 9%VS78 1% (p <0 0 5 ) ,差异具有显著性。化疗后选择单纯手术治疗的治疗方式 ,时辰新辅助化疗组与常规新辅助化疗组相比为 5 0 %VS 37 5 % (p <0 0 5 ) ,时辰新辅助化疗组Ⅲ、Ⅳ度白细胞下降显著低于常规新辅助化疗组 ,其余化疗近期毒副反应两组间无显著差异。结论　在宫颈癌的新辅助化疗中采用PF方案时 ,时辰新辅助化疗组的近期疗效高于常规新辅助化疗组 ,两组的化疗近期毒副反应基本相同 ,故在宫颈癌的新辅助化疗中可采用时辰化疗     

A phase II study of gemcitabine and cisplatin combination as induction chemotherapy for untreated locally advanced cervical carcinoma

Background:Cisplatin-based chemoradiation for locally advanced cervical carcinoma is now the standard of care for most patients with cervical carcinoma. However, induction chemotherapy followed by surgery, particularly with newer agents or combinations remains to be explored. This study was undertaken to evaluate the antitumor activity and toxicity of gemcitabine in combination with cisplatin for untreated locally advanced cervical carcinoma. Patients and methods:Open-label, single center, phase II, non-randomized study of neoadjuvant gemcitabine plus cisplatin. Forty-one patients with histologic diagnosis of cervical carcinoma, with no previous treatment and staged as IB2 to IIIB, were treated with three 21-day courses of cisplatin 100 mg/m² day 1 and gemcitabine 1000 mg/m² days 1 and 8, followed by locoregional treatment with either surgery or concomitant chemoradiation. Response and toxicity were evaluated before each course and at the end of chemotherapy. Results:All patients were evaluated for toxicity and 40 for response. The overall objective response rate was 95% (95% confidence interval (CI): 88%–100%) being complete in 3 patients (7.5%) and partial in 35 (87.5%). A complete pathological response was found in 6 (26%) of the 23 patients that underwent surgery. Granulocytopenia grades 3–4 occurred in 13.8% and 3.4% of the courses, respectively, whereas non-hematological toxicity was mild. Conclusions:Induction chemotherapy with the combination of gemcitabine and cisplatin is highly active for untreated cervical cancer patients and has an acceptable toxicity profile.