结直肠癌MICA基因的表达与p53、K-ras基因突变的关系研究

目的研究结直肠癌组织MICA基因的表达与肿瘤临床特征及p53、K-ras基因突变的关系。方法共纳入本院2014年3月-2016年3月66例结直肠癌患者,应用半定量PCR-SSCP技术检测癌组织MICA基因表达水平与p53、K-ras基因突变情况,分析MICA基因表达与肿瘤临床特征及p53、K-ras基因突变的关系。结果 MICA基因表达与结直肠癌患者的肿瘤部位、年龄和性别无相关性(P0.05)。22例淋巴结转移者的MICA平均表达量明显高于淋巴结未转移者,8例K-ras和p53基因联合突变者MICA基因平均表达量高于非联合突变者,12例K-ras基因突变者MICA平均表达量与未突变者,差异无统计学意义(P0.05),16例p53基因突变者MICA平均表达量显著高于未突变者。结论MICA基因高表达可能与肿瘤淋巴结转移及p53、K-ras基因突变密切相关。     

EGFR基因突变的非小细胞肺癌靶向治疗失败后再化疗研究

目的研究表皮生长因子受体(EGFR)基因突变的非小细胞肺癌(NSCLC)靶向治疗失败后再化疗治疗的临床方案及效果。方法选取该院2013年6月至2016年2月应用表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)靶向治疗失败的晚期NSCLC患者106例,根据患者病情分为最佳支持治疗(BSC)组24例、单药化疗组(采用多西他赛及培美曲塞治疗)35例、与铂类联合化疗组47例。21 d为1个化疗周期,2个周期后统计对比3组疾病控制率;随访1年,统计不同治疗方案无进展生存期(PFS)及生存期(OS)。结果与铂类联合化疗组疾病控制率为19.15%,虽高于单药化疗组的11.43%、BSC组的8.33%,但差异均无统计学意义(均P0.05);卡铂或顺铂联合化疗PFS、OS较最佳支持治疗、多西他赛化疗、培美曲塞单药化疗时间长,差异均有统计学意义(均P0.05)。结论 EGFR基因突变的非小细胞肺癌靶向治疗失败后应用多西他赛、培美曲塞单药化疗或与铂类联合化疗均可提高疾病控制率,尤其是与铂类联合化疗可延长患者生命周期。     

84例晚期结直肠癌K-ras基因突变情况研究

目的观察K-ras基因在晚期结直肠癌原发灶及对应转移灶中的突变情况。方法采用DNA直接测序法检测84例晚期结直肠癌患者原发灶及对应转移灶K-ras基因的突变情况。结果 26例原发灶及对应转移灶K-ras基因均为突变型;52例原发灶及对应转移灶K-ras基因均为野生型。原发灶及转移灶两者的一致率为92.86%,无统计学差异(p=1.00)。两者不一致的情况有6例(7.14%)。结论晚期结直肠癌原发灶和对应转移灶中K-ras基因的突变具高度一致性,可作为临床选用分子靶向药物的依据。     

替吉奥胶囊联合伊立替康治疗复发转移结直肠癌43例临床观察

目的探讨替吉奥胶囊联合伊立替康治疗复发转移结直肠癌的临床疗效。方法收集我院2009年1月-2013年1月收治的复发转移性结直肠癌86例,随机分为对照组采用伊立替康治疗,观察组在对照组的基础上给予替吉奥胶囊联合治疗。结果观察组治疗复发转移结直肠癌有效率为62．8％,对照组有效率44．2％,两组有统计学差异性（P〈0．05）;随访3～18个月,观察组在中位疾病进展时间与中位生存期比较中明显优于对照组（P〈0．65）。结论替吉奥胶囊联合伊立替康可作为治疗复发转移结直肠癌的一个有效地化疗方案,可有效提高有效率,提高控制疾病进展时间与生存期,值得在临床应用。     

雷替曲塞联合奥沙利铂与5-氟尿嘧啶、亚叶酸钙联合奥沙利铂治疗转移性结直肠癌的疗效比较

目的比较雷替曲塞联合奥沙利铂与5-氟尿嘧啶、亚叶酸钙联合奥沙利铂治疗转移性结直肠癌的临床疗效及不良反应。方法 47例转移性结直肠癌患者根据数字表法随机分为2组,雷替曲塞组(n=25例)采用雷替曲塞+奥沙利铂化疗治疗,5-氟尿嘧啶组(n=22例)采用5-氟尿嘧啶+亚叶酸钙+奥沙利铂化疗治疗。比较两组近期疗效、不良反应、中位疾病进展时间(TTP)、中位总生存期(OS)及1年生存率。结果雷替曲塞组有效率明显高于5-氟尿嘧啶组(P<0.05),两组疾病控制率比较无显著性差异(P>0.05);两组3-4级不良反应发生率比较无显著性差异(P>0.05),雷替曲塞组患者恶心呕吐、腹泻、口腔黏膜炎、中性粒细胞减少等1-2级不良反应发生率明显低于5-氟尿嘧啶组(P<0.05),转氨酶发生率明显高于5-氟尿嘧啶组(P<0.05);雷替曲塞组中位TTP明显高于5-氟尿嘧啶组(P<0.05),OS及1年生存率与5-氟尿嘧啶组比较无显著性差异(P>0.05)。结论雷替曲塞联合奥沙利铂治疗转移性结直肠癌的治疗有效率明显高于5-氟尿嘧啶、亚叶酸钙联合奥沙利铂方案,且不良反应少,值得临床广泛应用。     

结直肠癌k-ras突变与ERCC1mRNA表达相关性研究

目的:探讨结直肠癌k-ras基因突变与ERCC1mRNA表达相关性,为结直肠癌化疗提供理论依据.方法选择2012年1月~2014年6月间我院送检的结直肠癌病例92例,应用直接测序法检测肿瘤组织k-ras基因突变情况,应用RT-PCR相对定量分检测肿瘤组织ERCC1mRNA表达水平.结果:92例结直肠癌患者肿瘤组织中,共有29例发生了k-ras突变,突变发生率为31.5%.k-ras突变型患者ERCC1mRNA表达水平显著高于k-ras野生型患者(P<0.05).不同肿瘤长度、浸润深度、分化程度、临床分期及淋巴结转移患者ERCC1mRNA表达水平(△CT)无统计学差异(P>0.05).Pearson相关分析显示ERCC1mRNA表达水平与肿瘤长度、浸润深度、分化程度、临床分期及淋巴结转移无相关性(P>0.05),与k-ras突变发生呈正相关(r=0.667,P<0.05).结论:结直肠癌k-ras突变与ERCC1mRNA表达密切相关,二者可能与结直肠癌化疗联合西妥昔单抗治疗耐药有一定关系.     

恩度联合化疗对中晚期非小细胞肺癌患者PFS及OS的影响

目的探讨恩度联合化疗对中晚期非小细胞肺癌(NSCLC)患者无进展生存期(PFS)及总生存期(OS)的影响。方法选取2017年3月—2019年3月本院收治的确诊为中晚期NSCLC患者65例。随机分为2组,对照组32例,观察组33例。对照组采用单纯化疗治疗,观察组采用恩度联合化疗治疗。对比两组临床疗效、疾病无进展生存期(PFS)和总生存期(OS)以及血清肿瘤标志物水平。结果治疗3个疗程,观察组临床有效率略高于对照组,但差异无统计学意义(P0.05);观察组PFS、OS时间长于对照组,差异有统计学意义(P0.05);观察组癌胚抗原(CEA)、糖抗原(CA125)、细胞角蛋白19片段抗原(CYFRA21-1)水平均低于对照组,差异有统计学意义(P0.05)。结论恩度联合化疗治疗中晚期NSCLC效果确切,可有效降低肿瘤标志物水平,消除病症,从而延长患者生存周期,具有较高临床应用价值。     

辽宁本溪市中心医院 联合分子靶向治疗晚期肿瘤

东北地区是结肠癌和直肠癌的高发地区，能够早期确诊进行手术的病人不足1／3，局部复发和远处转移成为治疗失败的主要原因，晚期结、直肠癌患者在支持治疗下一般生存期为4-5个月。但国外研究显示，以分子靶向药物治疗，可使晚期转移性结肠癌、直肠癌的中位生存期提高至20个月。分子靶向治疗技术是有针对性地治疗晚期癌症的国际领先技术。     

豫西南地区结直肠癌患者EGFR、KRAS、BRAF基因突变与临床病理特征的关系

目的探讨豫西南地区结直肠癌患者表皮生长因子受体(EGFR)、Kirsten鼠肉瘤病毒癌基因(KRAS)、B-Raf原癌基因丝氨酸/苏氨酸蛋白激酶(BRAF)基因突变与临床病理特征的关系,为结直肠癌的精准医学及靶向治疗提供依据。方法选取2014年6月—2016年12月收治的结直肠癌手术切除患者268例,采用荧光定量PCR法检测EGFR基因18、19、20、21号外显子及KRAS基因12、13位密码子和BRAF基因15号外显子突变情况,比较不同临床病理特征的EGFR、KRAS、BRAF基因突变情况。结果豫西南地区结直肠癌患者EGFR、KRAS、BRAF基因突变频率分别为30%、30%、18.6%,EGFR基因突变类型为4种,以19-Del和L858R最常见,KRAS基因突变类型主要为Gly12Asp,BRAF基因突变类型主要为V600E。EGFR、KRAS基因在男性、年龄≥60岁患者中突变率均高于女性、年龄60岁患者(均P0.05),不同肿瘤部位、浸润深度及淋巴结转移的EGFR、KRAS、BRAF基因突变率比较,差异均无统计学意义(均P0.05)。结论豫西南地区结直肠癌患者中,EGFR、KRAS基因突变与性别、年龄有关,BRAF基因突变与患者性别、年龄无关,EGFR、KRAS、BRAF基因突变与肿瘤部位、浸润深度及淋巴结转移均无关。     

非小细胞肺癌EGFR基因突变与靶向治疗研究进展

肺癌男性发病率为第一位,女性发病率第二位,死亡率第一位。肺癌病理类型中80%为非小细胞肺癌(NSCLC),此类患者确诊时大多为晚期或局部晚期,丧失手术机会而采用放化疗等非根治性治疗。但以铂类为基础联合第三代化疗药物虽然能够延长患者生存期,但多数患者接受3个周期以上化疗后产生耐药。近年来随着分子生物学技术及靶向药物研发的进展,肺癌靶向治疗取得了长足的进步。以小分子酪氨酸激酶抑制剂为主靶向治疗能明显延长表皮生长因子受体(EGFR)存在19和21外显子突变的患者。EGFR基因19、21外显子突变,被认为是肺癌靶向治疗效果预测的重要分子标记。近年来随着肺癌靶向治疗的不断研究,EGFR基因突变状态与靶向药物疗效的关系得到了广泛的关注。本文对几年来关于NSCLC EGFR基因突变及靶向药物治疗研究的相关文献进行综述,以期为临床NSCLC的治疗提供参考。     

Skeletal Muscle Mass Predicts Poor Prognosis in Patients with Advanced Pancreatic Cancer Undergoing Second-Line FOLFIRINOX Chemotherapy

Objectives: Although the significance of skeletal muscle mass has been investigated in pancreatic cancer, there are no reports regarding the impact of skeletal muscle mass on prognosis in patients who have undergone second-line chemotherapy. We aimed to identify prognostic factors in patients with advanced pancreatic cancer treated with second-line FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin).

Methods: We retrospectively reviewed the data of 57 pancreatic cancer patients treated with second-line FOLFIRINOX. Age, sex, body mass index, Eastern Cooperative Oncology Group (ECOG) performance status, carbohydrate antigen 19-9 levels, skeletal muscle area, skeletal muscle index (SMI), progression free survival (PFS), and overall survival (OS) were analyzed.

Results: The median age of the 57 patients (male, 56.1%) was 60.4?years (38–78). Median PFS and OS were 2.6 and 6.6?months. On Kaplan-Meier curves, high SMI was associated with prolonged OS and PFS (P value?=?0.003 and 0.015). In multivariate analysis, baseline SMI was significant independent prognostic factor in patients treated with second-line FOLFIRINOX.

Conclusion: Baseline SMI has an impact on prognosis in patients who undergoing second-line chemotherapy for pancreatic cancer. Skeletal muscle mass may warrant consideration as a predictive factor with which to identify candidates for second-line chemotherapy for advanced pancreatic cancer.     

Irinotecan--experience with second-line treatment in advanced colorectal cancer]

The prognosis for patients with advanced colorectal cancer who fail to respond to a 5-FU based therapy is poor. About 7% response rate can be achieved with second line therapeutic regiments, the overall survival is about 6-7 months. The aim of authors was to assess the efficacy and toxicity profile of irinotecan (CAMPTO) in patients with advanced colorectal cancer, resistant to 5-FU based chemotherapy. From October 1996 to November 1998 19 previously treated metastatic colorectal cancer patients with documented progression were recruited. Irinotecan was given at a dose of 350 mg/m2 i.v. over 90 min. every 3 week. Tumor response and toxicity were assessed using WHO criteria. Median age: 59.7 years (42-72). Tumor sites: 12/19 colon, 7/19 rectum. 11/19 patients had 1 metastatic site, 8/19 had 2 or more metastatic sites. CR: 0/19, PR: 3/19, MR: 2/19, SD: 10/19, PD: 4/19. Median time to progression was 9.1 months (range 1.5-22). The overall median survival was 15.5 months (range 2.5-37). Grade 3-4 delayed diarrhoea occurred in 26.3% of patients. Grade 3 neutropenia occurred in 15.7% of patients. Preliminary results confirm the clinical value of irinotecan in 5-FU resistant metastatic colorectal cancer with tolerable toxicity profile. Irinotecan should be considered as the basic chemotherapeutic agent for second line treatment of metastatic colorectal cancer.     

Prognostic factors,patterns of recurrence and toxicity for patients with esophageal cancer undergoing definitive radiotherapy or chemo-radiotherapy

The aim of this study was to evaluate the effectiveness and tolerability of definitive chemo-radiation or radiotherapy alone in patients with esophageal cancer. We retrospectively analyzed the medical records of n = 238 patients with squamous cell carcinoma or adenocarcinoma of the esophagus treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2000 and 2012. Patients of all stages were included to represent actual clinical routine. We performed univariate and multivariate analysis to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). Moreover, treatment-related toxicity and patterns of recurrence were assessed. Patients recieved either chemo-radiation (64%), radiotherapy plus cetuximab (10%) or radiotherapy alone (26%). In 69%, a boost was applied, resulting in a median cumulative dose of 55.8 Gy; the remaining 31% received a median total dose of 50 Gy. For the entire cohort, the median OS and PFS were 15.0 and 11.0 months, respectively. In multivariate analysis, important prognostic factors for OS and PFS were T stage (OS: P = 0.005; PFS: P = 0.006), M stage (OS: P = 0.015; PFS: P = 0.003), concomitant chemotherapy (P < 0.001) and radiation doses of >55 Gy (OS: P = 0.019; PFS: P = 0.022). Recurrences occurred predominantly as local in-field relapse or distant metastases. Toxicity was dominated by nutritional impairment (12.6% with G3/4 dysphagia) and chemo-associated side effects. Definitive chemo-radiation in patients with esophageal cancer results in survival rates comparable with surgical treatment approaches. However, local and distant recurrence considerably restrict prognosis. Further advances in radio-oncological treatment strategies are necessary for improving outcome.     

复合型小细胞食管癌的治疗策略

目的 探讨复合型小细胞食管癌(Combined small cell esophageal cancer,C-SCEC)临床特征及预后因素,并明确手术,放疗及化疗的价值。方法 回顾分析1989年1月-2012年4月天津医科大学肿瘤医院收治的32例复合型小细胞食管癌患者的临床资料。采用Kaplan-Meier法行生存分析,Log-rank法单因素预后分析。结果 本组29例患者获得随访,随访率为90.6%。中位生存期13.7月(4.3~86.5月);1、2、3年总生存率分别为55.3%、31.6%、15.8%。单因素分析显示TNM分期(P=0.01),N分期(P=0.01)及M分期(P=0.02)为影响预后的因素。化疗周期数大于等于4及先局部治疗(手术或放疗)后化疗的治疗方案有提高患者生存趋势(P=0.23和P=0.09)结论 复合型小细胞食管癌病变相对局限,以综合治疗为主,TNM分期,N分期及M分期是影响预后的因素。手术联合放化疗或许能够提高患者生存趋势。     

吉非替尼联合择期放疗治疗晚期非小细胞肺癌的临床研究

目的 观察吉非替尼联合择期放疗治疗晚期非小细胞肺癌(NSCLC)的疗效和不良反应.方法 13例晚期NSCLC,应用吉非替尼治疗,对10例吉非替尼治疗获益的患者,根据患者及家属意愿分为联合组和对照组,每组5例,联合组联合放疗,对照组继续单独应用吉非替尼治疗直至病情进展.结果 到随访截止日期,全部患者1年生存率达53.8%(7/13),2年生存率达46.2%(6/13).联合组和对照组的中位无进展生存期(PFS)分别为24个月和8个月(P=0.0019),中位总生存期(OS)分别为32个月和10个月(P=0.0062).不良反应主要为皮疹和腹泻.无症状性肺纤维化3例.结论 吉非替尼联合择期放疗治疗晚期NSCLC可以显著延长PFS和OS,不良反应可以耐受,是NSCLC规范化治疗和个体化治疗的合理选择.

Abstract：

Objective To study the effect and toxicity ofgefitinib combined with selected radiotherapy in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Methods From March 2006 to February 2009,10 of 13 advanced NSCLC patients who got benefit from gefitinib were enrolled to treatment group (gefitinib concurrent selected radiotherapy) and control group (gefitinib only), with 5 cases in each group. The response was evaluated as progression free survival (PFS) and overall survival (OS).Results No patient got complete remission (CR). Ten of 13 patients got partial remission (PR) and stable disease (SD). The 1 year and 2 years survival rate was 53.8%(7/13) and 46.2%(6/13) respectively. The median PFS in treatment group and control group was 24 months and 8 months respectively(P= 0.0019). The median OS was 32 months and 10 months respectively (P= 0.0062). The main toxicities were reversible skin rash and diarrhea,and 3 patients developed asymptomatic radiation pulmonary fibrosis. Conclusions Gefitinib combining with selected radiotherapy is effective and tolerated in patients with advanced NSCLC. It may prolong PFS and OS. It may be a rational choice for the standard and individualized treatment of NSCLC.     

Treatment outcomes of definitive chemoradiotherapy for patients with hypopharyngeal cancer

We analyzed the efficacy of definitive chemoradiotherapy (CRT) for patients with hypopharyngeal cancer (HPC). Subjects comprised 97 patients who were treated with definitive CRT from 1990 to 2006. Sixty-one patients (62.9%) with resectable disease who aimed to preserve the larynx received induction chemotherapy (ICT), whereas 36 patients (37.1%) with resectable disease who refused an operation or who had unresectable disease received primary alternating CRT or concurrent CRT (non-ICT). The median dose to the primary lesion was 66 Gy. The median follow-up time was 77 months. The 5-year rates of overall survival (OS), progression-free survival (PFS), local control (LC), and laryngeal preservation were 68.7%, 57.5%, 79.1%, and 70.3%, respectively. The T-stage was a significant prognostic factor in terms of OS, PFS and LC in both univariate and multivariate analyses. The 5-year rates of PFS were 45.4% for the ICT group and 81.9% for the non-ICT group. The difference between these groups was significant with univariate analysis (P = 0.006). Acute toxicity of Grade 3 to 4 was observed in 34 patients (35.1%). Grade 3 dysphagia occurred in 20 patients (20.6%). Twenty-nine (29.8%) of 44 patients with second primary cancer had esophageal cancer. Seventeen of 29 patients had manageable superficial esophageal cancer. The clinical efficacy of definitive CRT for HPC is thought to be promising in terms of not only organ preservation but also disease control. Second primary cancer may have a clinical impact on the outcome for HPC patients, and special care should be taken when screening at follow-up.     

小细胞肺癌治疗62例分析

目的 比较小细胞肺癌的治疗模式及治疗效果.方法 1、2期小细胞细胞肺癌患者62例A组（32例）行手术治疗,术后给予放化疗,B组（30例）单纯给予放化疗.结果 A组中位生存时间为50个月,1、2、3年生存率分别为96%、70%、52%,B组总中位生存时间为48个月,1、2、3年生存率分别为93%、71%、48%;A组术后治疗中或治疗后出现转移病灶的情况依次为：失败原因包括局部复发（12%）、远处转移（32%）、局部复发加远处转移（8%）和脑转移（19%）,B组失败原因包括局部复发（14%）、远处转移（30%）、局部复发加远处转移（9%）和脑转移（29%）.手术＋化疗＋放疗组与放化疗组的生存率差异无统计学意义（P〉0.05）.结论 手术＋化疗＋放疗和放化疗对临床Ⅰ、Ⅱ期小细胞肺癌的治疗均有较好的疗效.     

高分辨率熔解曲线分析检测大肠癌患者粪便基因突变与临床病理参数的关系

目的初步探讨高分辨率熔解曲线分析检测大肠癌患者粪便DNA突变与临床病理参数的关系。方法收集2009年3月～2009年9月在本院住院的39例大肠癌患者的新鲜粪便标本约1g,应用HRM法检测粪便中APC、K-ras、P53基因的突变情况,并对结果进行统计学分析。结果大肠癌患者粪便中APC、K-ras、P53基因的突变与大肠癌患者性别、年龄、分化状态、病变部位、Dukes分期和有无淋巴结转移无关。结论未发现粪便APC、K-ras和P53基因突变情况与大肠癌患者的临床病理参数具有相关性。     

Vitamin D Supplementation and Survival in Metastatic Colorectal Cancer

Background: Some studies have demonstrated that higher baseline plasma levels of 25-hydroxivitamin D [25(OH)D] are associated with a significant reduction in colorectal cancer (CRC) incidence. Patients with metastatic CRC (mCRC) tend to be vitamin D insufficient, but the effect of vitamin D on the survival of mCRC patients still remains uncertain. In this study, we evaluated the association between cholecalciferol 2,000 IU daily supplementation and survival of mCRC patients. Methods: Seventy-two patients with mCRC were included. Seventy-one patients with 25(OH)D levels <75 nmol/l were randomized to receive standard chemotherapy or standard chemotherapy with cholecalciferol 2,000 IU daily. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). The follow-up period was 46 mo. Results: All but one patient (98.6%) was vitamin D insufficient. There was no statistically significant difference in OS or PFS between those who received vitamin D supplements and controls. Conclusions: The majority of patients with mCRC are vitamin D insufficient at the time of diagnosis. In our study, adding 2,000 IU of cholecalciferol daily for 2 yr to standard chemotherapy did not show any benefit in OS or PFS.