局部进展期直肠癌新辅助化疗后病理完全缓解及肿瘤降期的预测因素分析

目的:探索局部进展期直肠癌(LARC)经新辅助化疗后病理完全缓解（pCR）和肿瘤降期（ypT0-1）的预测因素。方法:回顾性分析71例经新辅助化疗后进行全直肠系膜切除术的局部进展期直肠癌患者的临床资料,分析其临床特征,筛选经新辅助化疗后达到pCR及肿瘤降期（ypT0-1）的预测因子。结果:单因素分析结果显示肿瘤占肠腔＜1/2周（P＜0.001）、基线CEA≤5 ng/mL（P=0.001）、基线临床N分期为N0期（P=0.019）以及新辅助治疗2周期后影像评估为缓解（P=0.002）与直肠癌新辅助化疗后的高pCR率有关;肿瘤占肠腔＜1/2周（P＜0.001）、基线CEA≤5 ng/mL（P=0.029）以及新辅助治疗2周期后影像评估为缓解（P=0.007）与直肠癌新辅助化疗后的高肿瘤降期率（ypT0-1）有关。多因素Logistic回归分析结果显示,肿瘤占肠腔环周大小（P=0.013）、基线CEA水平（P=0.042）以及基线临床N分期（P=0.038）是影响直肠癌新辅助化疗后pCR的独立预测因子;肿瘤占肠腔环周大小（P=0.001）是影响直肠癌新辅助化疗后肿瘤降期（ypT0-1）的独立预测因子。结论:初始诊断时肿瘤占肠腔环周大小、基线CEA水平及淋巴结是否阳性对局部进展期直肠癌新辅助化疗后pCR有预测作用,肿瘤占肠腔环周大小对局部进展期直肠癌新辅助化疗后肿瘤降期（ypT0-1）有预测作用。     

非小细胞肺癌新辅助化疗后肿瘤体积变化规律及其影响因素

目的:探讨非小细胞肺癌（NSCLC）新辅助化疗后肿瘤体积变化规律及其影响因素。方法:回顾性分析2010年1月至2013年12月在我院肿瘤科确诊并治疗的80例NSCLC患者,使用治疗计划系统（TPS）自带体积测量软件及ImageJ图像处理软件对肿瘤体积进行测量,分析比较不同新辅助化疗周期后肿瘤体积变化情况及其可能的影响因素。结果:化疗1周期后,NSCLC患者平均原发灶肿瘤体积由（89.33±29.24）cm3降至（58.36±23.62）cm3,差异具有统计学意义（t=7.369,P<0.01）;化疗2、3、4周期后, 肿瘤体积变化不显著（P>0.05）;化疗第5周期后,肿瘤体积较第4周期增大（P<0.01）;但第6周期较第5周期无明显变化（P>0.05）。对可能影响化疗1周期后肿瘤体积变化的因素进行单因素分析显示,原发灶肿瘤体积及T分期对化疗1周期后肿瘤体积变化的影响有统计学意义（P<0.05）,而患者的性别、年龄、肿瘤分类、肿瘤部位以及病理类型与其无关。Logistic回归分析显示,原发灶肿瘤体积及T分期均是影响化疗1周期后肿瘤退缩率的独立影响因素(P均<0.05）。结论:NSCLC新辅助化疗1周期肿瘤体积回缩最显著,原发灶肿瘤体积和T分期是影响化疗1周期后疗效的独立因素,建议新辅助化疗1周期后开始介入放疗或同步放化疗。     

TEM1表达与胃癌患者新辅助化疗疗效相关性研究

  目的  检测胃癌组织中P53、人表皮生长因子受体2（HER-2）、肿瘤内皮标记物1（TEM1）的表达情况,结合新辅助化疗后临床疗效进行相关性分析,探讨其作为新辅助化疗疗效生物学标志物的可能性。  方法  选取2015年5月至2017年5月于兰州大学第一医院就诊以氟尿嘧啶为基础行新辅助化疗的63例胃癌患者,对新辅助化疗前的胃癌标本行免疫组织化学法检测P53、HER- 2、TEM1的表达情况,通过影像学评估新辅助化疗疗效,分析各肿瘤指标与新辅助化疗疗效之间的关系。  结果  63例进展期胃癌患者新辅助化疗后总有效率为69.8%,其中完全缓解（complete response,CR）2例,部分缓解（partial response,PR）7例,疾病稳定（stable disease,SD）35例,疾病进展（progressive disease,PD）19例;单因素分析结果显示TEM1阳性、T分期较高的患者新辅助化疗疗效较差（均P < 0.05）;病变部位、分化程度、病灶大小、P53（P=0.488）阳性及HER-2（P=0.106）阳性表达与胃癌新辅助化疗疗效无相关。多因素分析结果显示TEM1阳性、T分期高可能是进展期胃癌患者新辅助化疗疗效差的预测因素。  结论  TEM1作为肿瘤基质的标志物,其阳性表达可能成为预测胃癌新辅助化疗疗效差的重要分子生物学指标。      

局部晚期直肠癌新辅助治疗后病理完全缓解者的预后分析

目的:总结局部晚期直肠癌新辅助治疗后病理完全缓解（pCR）者的长期预后,探讨术后辅助化疗的必要性。方法:回顾性分析2005年至2014年间,323例在我院进行新辅助治疗及根治性手术的局部晚期直肠癌患者的临床资料,分析pCR者的长期预后,同时比较术后辅助化疗组和术后未化疗组的预后。结果:52例（16.1%）获得pCR,其中1例患者失访;全组患者中位随访时间为53个月,全组5年无病生存率和总生存率分别为82.7%和90.9%。其中22例（43.1%）患者接受术后辅助化疗,29例（56.9%）未接受术后化疗。两组患者的性别、年龄、肿瘤临床分期、肿瘤位置、大小、分化程度、术前CEA水平、新辅助化疗的方案、新辅助治疗结束至手术的间隔周期、手术方式、术后并发症、淋巴结清扫的数目以及随访时间均无统计学差异。两组患者的5年无病生存率以及总生存率亦无统计学差异。结论:局部晚期直肠癌新辅助治疗后病理完全缓解者可获得良好的生存预后;对于pCR者,实施术后辅助化疗不会影响其预后。     

新辅助化疗与放疗间断对鼻咽癌总生存的影响*

目的:探讨较强烈的新辅助化疗和放疗间断对鼻咽癌患者长期生存的影响。方法:选取1995年1 月至1998年12月福建省肿瘤医院1 706 例鼻咽癌患者接受或不接受新辅助化疗,1 081 例患者单纯放疗,而625 例接受1 个疗程较强烈的新辅助化疗。化疗方案以DDP 为基础,每14天为1 个周期,多为2～3 个周期,放疗在最后一次化疗结束后2～5 天开始。化疗包括:DDP80mg/m2分3 天（d1～d3）静脉推注;5-FU 750mg/（m2·d）,连续5 天（d1～d5）静脉滴注。1 706 例患者中有177 例患者由于各种原因造成放疗间断1 周以上。分析患者、肿瘤和治疗等因素对长期生存的影响,尤其是新辅助化疗和放疗间断对生存的影响。结果:中位随访时间75个月（6～126 个月）,失访162 例,随访率为90.50% 。3 年和5 年生存率分别为79.2% 和67.6% 。多因素分析显示性别、年龄、治疗前贫血、肿瘤分期、是否采用新辅助化疗以及放疗是否间断等是影响长期生存的独立预后因素。Ⅰ、Ⅱ、Ⅲ和Ⅳ期的5 年生存率分别为100.0% 、75.9% 、66.5% 和49.3%（P<0.05）。 Ⅲ/Ⅳ期患者中接受与不接受辅助化疗的5 年总生存率分别为65.3%（95%CI:0.796～0.869）和60.5%（95% CI:0.755～0.824）（P=0.041）。 放疗间断与放疗不间断的5 年总生存率分别为51.69%（95% CI:0.449～0.584）和69.45%（95% CI:0.672～0.717）（P<0.001）。 结论:较强烈的新辅助化疗和放疗过程的不间断是鼻咽癌患者长期生存的有利因素。      

乳腺癌TAC新辅助化疗与相关不良预后因素的关系分析

目的 探讨乳腺癌紫杉醇+环磷酰胺+吡柔比星（TAC）方案新辅助化疗与相关不良预后因素的关系。方法 分析1561例乳腺癌患者（TAC新辅助化疗180例）同侧淋巴结转移、锁骨上淋巴结转移、残余脉管内肿瘤和肿瘤结节的发生情况。结果 接受TAC新辅助化疗的乳腺癌患者同侧淋巴结转移率、锁骨上淋巴结转移率、残余脉管内肿瘤发生率和肿瘤结节发生率均高于直接手术患者（P﹤0.01）。轻度缓解和部分缓解患者同侧腋窝淋巴结转移率和残余脉管内肿瘤发生率均高于病理学完全缓解（pCR）患者,差异均有统计学意义（P﹤0.01）。结论TAC新辅助化疗可能提高乳腺癌同侧淋巴结转移率、锁骨上淋巴结转移率、残余脉管内肿瘤发生率和肿瘤结节发生率,尤其新辅助化疗效果不佳的患者,可能增加潜在复发与转移风险。     

三阴性乳腺癌组织中PD 1表达情况与临床病理特征及新辅助化疗疗效相关性的研究

目的探讨三阴性乳腺癌（TNBC）患者肿瘤组织中程序性死亡受体1（PD 1）的表达情况与患者临床病理特征及新辅助化疗疗效等指标的关系。方法选取南京医科大学第一附属医院2012年12月3日至2020年1月20日具有完整病理和临床数据的22例女性TNBC新辅助化疗患者肿瘤组织的蜡块,采用免疫组化染色检测PD 1在组织中的表达,探讨PD 1的表达与TNBC患者临床病理特征的关系。结果通过影像学及病理学评估,PD 1阳性患者新辅助化疗疗效显著优于阴性患者（P<005）。结论TNBC患者肿瘤组织中PD 1的表达情况具有预测TNBC患者新辅助化疗疗效的潜能。     

激素受体和HER-2及Ki-67预NSL腺癌新辅助化疗疗效价值的分析

目的：探讨乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）及Ki-67的表达状态对新辅助化疗反应的预测作用以及化疗前后其表达差异对疗效的影响。方法：免疫组织化学方法检测新辅助化疗前后118例乳腺癌组织的ER、PR、HER-2及Ki-67的表达情况,并分析其与新辅助化疗疗效的关系。结果：118例新辅助化疗乳腺癌病例中,ER-和PR-组pCR分别为26．1％和27．1％,明显高于ER＋组11．1％和PR＋组6．8％,P-0．003。HER-2和Ki-67的表达对新辅助化疗疗效无显著影响。新辅助化疗前ER、PR与Ki-67的表达呈明显负相关,P〈0．001;新辅助化疗后Ki-67的高表达病例数显著减少,P-0．001。结论：ER-／PR-的患者对新辅助化疗更为敏感,Ki-67在化疗后发生了显著下调,提示新辅助化疗能降低肿瘤的增殖活性。ER、PR及Ki-67可以作为新辅助化疗疗效的预测指标。     

乳腺癌新辅助化疗86例临床观察

目的：观察乳腺癌新辅助化疗的临床效果，并探讨其临床价值。方法：2004年6月-2007年2月收治乳腺癌患者86例，予以新辅助化疗（rIThpC方案），即：多西紫杉醇（艾素）100mg，d1；吡柔比星60mg，d1；环磷酰胺0．8g，d1。21d为1周期，2—5个周期后观察客观有效率、病理缓解率及新辅助化疗前后免疫组化指标的变化。结果：新辅助化疗后临床完全缓解（cCR）者19例，占22．09％，部分缓解（cPR）者51例，占59．30％，病情稳定（SD）者16例，占18．60％，无疾病进展（PD）患者；病理学完全缓解（pCR）者7例，占8．14％。21例患者新辅助化疗后的ER、PR、C-erbB-2的阳性表达率均低于新辅助化疗前，但未达到统计学差异（P〉0．05）。结论：乳腺癌新辅助化疗可以有效的缩小肿瘤，降低肿瘤分期，提高行改良根治术及保乳术几率，逆转可能存在的全身转移，为化疗方案提供药敏依据；新辅助化疗可使乳腺癌患者ER、PR、C-erbB-2的阳性表达降低，临床应根据术前免疫组化结果制定相关术后辅助治疗方案，才可能使患者有更大的获益。     

新辅助化疗对乳腺癌患者survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的影响及其疗效预测意义

目的探讨新辅助化疗对乳腺癌survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的影响,同时研究这些指标对新辅助化疗的疗效预测作用。方法通过免疫组织化学S-P法检测和HE染色对化疗前空芯针穿刺标本和化疗后手术切除的30例乳腺癌组织的survivin、Ki-67、ER、C-erbB-2、p53和肿瘤组织学分级的表达情况。化疗方案为CAF（CTX 600 mg/m^2,THP 50 mg/m2,5-FU500 mg/m^2）和TA（艾素75 mg/m^2,THP 30 mg/m^2）,每3周1疗程,用药2～3个疗程。化疗疗效通过采用临床体检、乳腺彩超检测及术后病理分析综合判断。结果 30例患者中70.0%（21/30）获PR,SD为30.0%（9/30）,全组无恶化病例,总有效率为70.0%（21/30）。通过对化疗前后的指标比较发现：新辅助化疗能降低Ki-67的表达（P〈0.01）和肿瘤分级（P〈0.05）。化疗前后survivin、ER、C-erbB-2和p53表达无明显变化（P〉0.05）。Ki-67高表达（≥20%）、肿瘤分级高的患者和Ki-67低表达（〈20%）、肿瘤分级较低的患者相比,化疗疗效更明显（P〈0.05）。结论新辅助化疗能显著降低乳腺癌组织Ki-67的表达和肿瘤分级,而对survivin、ER、C-erbB-2和p53表达均无显著影响,Ki-67高表达（≥20%）、肿瘤分级高的患者对化疗更敏感、短期疗效更显著。     

Bronchoscopic intratumoral chemotherapy of lung cancer

Described in this review is a therapeutic procedure for localized chemotherapy of lung cancer by bronchoscopic intervention. This procedure involves the intratumoral injection of one or several conventional cytotoxic drugs directly into tumor tissue through a flexible bronchoscope by means of an ordinary needle-catheter, and is termed "endobronchial intratumoral chemotherapy" (EITC). Intratumoral (IT) chemotherapy should not be considered merely an ablation technique for treatment of endobronchial tumor bulk such as other ablative endoscopic procedures. EITC rather affords a significant specific chemotherapeutic effect on malignant cells through the localized action of cytotoxic drugs. Although superficially similar to ablative methods such as brachytherapy and photodynamic therapy, EITC provides the multiple benefits of rapid initial eradication of tumor burden inside the airway lumen plus intratumoral delivery of cytotoxic drugs as a loco-regional neoadjuvant therapeutic modality prior to irradiation or surgery. It is localized chemotherapy which differs from intravenous chemotherapy by the route of delivery and mode of action. The manifold advantages of the EITC intratumoral injection procedure include (1) precise delivery of cancer drugs to and within the tumor, (2) complete perfusion of the lesion, (3) dramatically higher intratumor drug concentrations than possible by systemic drug delivery, and (4) virtually none of the toxic side effects which normally occur with conventional systemic chemotherapy. In this comprehensive review of endobronchial intratumoral chemotherapy of lung cancer via bronchoscopic needle-catheter our objective is to describe the clinical procedure, the outcomes, and the advantages for this neoadjuvant therapeutic procedure.     

Supplementary granulocyte macrophage colony‐stimulating factor to chemotherapy and programmed death‐ligand 1 blockade decreases local recurrence after surgery in bladder cancer

Despite advances and refinements in surgery and perioperative chemotherapy, there are still unmet medical needs with respect to radical cystectomy for muscle‐invasive bladder cancer (MIBC). We investigated the potential benefit of supplementary granulocyte macrophage colony‐stimulating factor (GM‐CSF) to chemoimmunotherapy with programmed cell death protein‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) axis blockade and standard neoadjuvant chemotherapy in bladder cancer. We inoculated 2 × 10⁵ MBT2 cells s.c. in C3H mice to create a syngeneic animal model of local recurrence (LR). When the tumor diameter reached 12 mm, the mice were allocated randomly as follows: (i) non‐treated control (vehicle only); (ii) anti‐mPD‐L1 monotherapy; (iii) mGM‐CSF monotherapy; (iv) anti‐mPD‐L1 plus mGM‐CSF; (v) gemcitabine and cisplatin (GC); (vi) GC plus anti‐mPD‐L1; (vii) GC plus mGM‐CSF; and (viii) GC plus anti‐mPD‐L1 plus mGM‐CSF. After completing 2‐week neoadjuvant therapy, tumors were resected for resection margin evaluation and immunohistochemical staining and blood was collected for flow cytometry and ELISA. Operative wounds were sutured, and the operative site was monitored to detect LR. Addition of anti‐mPD‐L1 and mGM‐CSF to neoadjuvant GC chemotherapy enhanced the antitumor effect and reduced positive resection margins (50% vs 12.5%). Combination of GC, anti‐mPD‐L1, and mGM‐CSF resulted in longer LR‐free survival and cancer‐specific survival compared to those in other groups. These effects involved an immunotherapy‐related decrease in oncological properties such as tumor invasion capacity and epithelial‐mesenchymal transition. mGM‐CSF significantly decreased the accumulation of myeloid‐derived suppressor cells in both the blood and tumor microenvironment and blood interleukin‐6 levels. Supplementary GM‐CSF to neoadjuvant GC plus PD‐L1 blockade could decrease LR after radical surgery by immune modulation in the blood and tumor microenvironment.     

术前介入化疗治疗宫颈癌56例疗效分析

目的:探讨宫颈癌术前介入化疗的近期疗效。方法:对56例宫颈癌患者实施术前介入化疗,抗癌药物选择顺铂、丝裂霉素、阿霉素或表阿霉素;部分病例在灌注化疗(2/3量抗癌药物)后用携带有抗癌药物(1/3量)的明胶海绵颗粒栓塞肿瘤供血动脉,观察近期临床及组织学疗效及不良反应,并对有手术指征者及时实行宫颈癌根治术。结果:56例介入化疗患者临床症状缓解率为100%,肿瘤消退情况8例完全缓解(CR),35例部分缓解(PR),13例无变化(NC),无疾病进展(PD),总有效率为76%,与化疗前相比肿瘤体积显著缩小(P<0.05)。56例标本严格按规定进行组织学评定,组织学有效率为82.1%(46/56),组织学完全缓解率为10.7%(6/56)。51例患者介入化疗后顺利完成根治手术,手术切除率达91%。仅有5例中、晚期宫颈癌病人无法手术,改用放疗。结论:宫颈癌术前介入化疗可以改善临床症状,缩减肿瘤体积和范围,降低肿瘤分期、提高手术切除率及减少术中出血,是一种安全、有效的局部治疗方法。     

Impact of neoadjuvant chemotherapy on the immune microenvironment in advanced epithelial ovarian cancer: Prognostic and therapeutic implications

Over the last decade, increasing evidence highlights the role of the host immune system in the control of tumor growth and the prognostic implications of tumor infiltrating lymphocytes (TILs) in ovarian cancer. Most data support a better prognosis with accumulation of CD3+ and CD8 + TILs and a poor outcome associated with increased regulatory T cells. However, only a small number of studies have focused on the effect of neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment. This review will provide an update on the prognostic value of TIL subpopulations at diagnosis and a comprehensive overview of the recent studies evaluating the impact of neoadjuvant chemotherapy on TILs and their relationship to clinical outcome in advanced ovarian cancer. This information could help in future investigations of immunotherapy as maintenance following primary treatment.     

喉癌术前平阳霉素诱导性化疗的临床及基础研究

Objective： To evaluate the short-term effects of neoadjuvant chemotherapy with pingyangmycin （PYM） in the treatment of laryngeal squamous cell carcinoma. Methods： 24 cases of laryngeal squamous cell carcinoma were treated with PYM before the operation, and the surgeries were undergone within one week after neoadjuvant chemotherapy. PCNA, p53, Bcl-2 and CD44v6 were detected in the specimens of tumor, retreated tumor and normal tissue using immunohistochemical methods. Results： Apoptosis could be detected more often in specimens with tumor and retreated tumor after chemotherapy than that before. The expression of PCNA, p53, Bcl-2 and CD44v6 in tumor tissue after neoadjuvant chemotherapy with PYM was weaker than that before the chemotherapy. There was significant difference in the positive ratio of PCNA, p53, Bcl-2 and CD44v6 between retreated tumor and tumor. Conclusion： After neoadjuvant chemotherapy with PYM, a large number of tumor cells died. The amplification and metastasis of tumor were suppressed by neoadjuvant chemotherapy with PYM.     

EFFECT OF NEOADJUVANT CHEMOTHERAPY USING PACLITAXEL COMBINED WITH CARBOPLATIN ON ADVANCED NON-SMALL CELL LUNG CANCER

Objeetive： To assess the therapeutic effectiveness of preoperative neoadjuvant chemotherapy using a combination of paclitaxel and carboplatin on local advanced non-small cell lung cancer （NSCLC）. Methods： Twenty-five patients with advanced NSCLC were treated with paclitaxel and carboplatin for 2 to 4 cycles before undergoing tumor resection and then postoperative chemotherapy/radiotherapy therapy for 2 to 4 cycles. Results： Following neoadjuvant chemotherapy, the most prominent side-effect was bone marrow restraint. The overall response rate of preoperative chemotherapy was 56%. The mean survival time was 26.5 months, with 1-, 2- and 5-year survival rates of 55%, 25%, and 16%, respectively. All NSCLC patients survived the perioperative period. Conclusion： Preoperative neoadjuvant chemotherapy combining paclitaxel and carboplatin produced minimal side-effect while increasing the probability that advanced NSCLC patients would be able to undergo surgery thus improving their prognosis.     

Clinical impact of chemotherapy to improve tumor microenvironment of pancreatic cancer

A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells. With the better understanding of the cell components in the tumor microenvironment and the effect of chemotherapy to improve tumor microenvironment, it has been gradually clear that the chemotherapeutic agents is two-edged sword to have both immune promoting and suppressing effects. The cellular components of the tumor microenvironment include infiltrating T lymphocytes, dendritic cells, regulatory T cells, tumor associated macrophages, myeloid derived suppressor cells and cancer associated fibroblasts. Based on the better understanding of tumor microenvironment following chemotherapy, the treatment protocol could be modified as personalized medicine and the prognosis of pancreas cancer would be more improved utilizing multimodal chemotherapy. Here we review the recent advances of chemotherapy to improve tumor microenvironment of pancreatic cancer, introducing the unique feature of tumor microenvironment of pancreatic cancer, interaction between anti-cancer reagents and these constituting cells and future prospects.     

Neoadjuvant intra-arterial infusion chemotherapy for invasive thymoma

Four patients with stage III or IVa invasive thymoma successfully underwent surgical intervention and radiotherapy following neoadjuvant intra-arterial chemotherapy including 50 mg/m(2) of cisplatin and 20 mg/m(2) of adriamycin. Remarkable reduction rates (60% or more) of the tumor size were obtained without significant side effects. About 4 weeks after neoadjuvant chemotherapy, an extended thymectomy including invaded organs was easily performed with a small amount of intraoperative bleeding. All patients but one are currently alive and disease-free. This method may be a new therapeutic strategy in the management of invasive thymoma.