非小细胞肺癌的放射治疗进展

非小细胞肺癌（NSCLC）放射治疗的研究进展包括三个方面。局部晚期病例的化放综合治疗,序贯化放疗能够提高生存率,化疗能够降低过远处转移率,对局部控制率没有显示明显的作用。而同时化放疗是治疗NSCLC很有希望的方法。非小细胞肺癌术后放疗的研究显示,Ⅰ、Ⅱ期病例术后放疗对总生存率有负相影响,放疗组非肿瘤死亡的增加。ⅢA期病例因单纯手术后复发和死亡率高,有必要地行要后辅助治疗,但术后放疗对局部控制率和生存率的作用仍不清楚。3D－CRT治疗的适应证、最佳治疗体积（靶区）、总剂量和分割剂量正在临床研究探索之中。其最终临床治疗价值－对局部控制率和生存率的作用,需要临床资料的积累和验证。     

Investigation the Role of Autophagy in Non-Small Cell Lung Cancer

Objective: Recent studies have shown the role of autophagy in different types of cancer including lung cancer. MicroRNAs are considered as key factors in regulation of autophagy related genes. miR-30d, miR-204-5p and miR-20a are regulatory markers which can suppress the expression of beclin1, LC3, bcl2 and ULK1 as their target genes and they lead to decrement of autophagy in human cancer cells. Moreover, epigenetic modifications DNA methylation has been indicated in regulation of autophagy in different stages of cancer. Methods: In this study, the expression levels of miR-30d, miR-204-5p and miR-20a as well as their target genes were analyzed in 30 non-small cell lung cancers (NSCLCs) patients sample and adjacent normal tissues by real-time qPCR. In addition, DNA methylation of beclin1, LC3, bcl2 and ULK1 genes were assessed by MS-HRM method. Results: MiR-30d (p value= 0.01) and miR-204-5p (P=0.048) significantly down-regulated in tumor samples compared to normal adjacent tissues, while there was no significant change in expression level of miR-20a. On the other hand, target genes expression level was significantly increased in NSCLC tissues, however methylation pattern of the target gene promoters, did not show any significant alteration. Conclusion: These results indicate roles for miR-30d, miR-204-5p as tumor suppressor genes as well as target genes as oncogenes in NSCLC patients. Although these factors may have a significant role in NSCLC progression, further studies are necessary to investigate the implications of these findings for treatment of lung cancer.     

异环磷酰胺治疗晚期非小细胞肺癌的疗效观察

[目的]观察异环磷酰胺(IFO)为主的方案治疗晚期非小细胞肺癌的疗效和毒副反应。[方法]采用IAP或IEP方案治疗晚期非小细胞肺癌38例 ,IFO1 4g/m2d1～5;DDP25mg/m2d1～3;ADM30mg/m2d 1 或Vp1660mg/m2d1～3。[结果]鳞癌有效率35 7 %(5/14) ;腺癌有效率为45.0%(9/20) ;总有效率39 5%(15/38)。主要毒副反应为骨髓抑制 ,发生率为39 5 %。[结论]IFO联合化疗方案治疗晚期非小细胞肺癌有效率较高 ,毒副反应可以耐受 ,值得临床进一步推广。     

非小细胞肺癌术后辅助化疗的共识

近年来有关非小细胞肺癌术后辅助化疗的治疗标准发生了显著变化,越来越多的前赡性、大样本随机临床试验和多项荟萃分析均证实辅助化疗,特别是新一代化疗药物的含铂联合方案能显著提高化疗反应和总体生存期,降低死亡危险比,且毒性反应均可耐受.因此,对于完整手术后的非小细胞肺癌,特别是Ⅰ B～Ⅱ期的患者采用辅助化疔是合理治疗方案.     

Association of Operability With Post-Treatment Mortality in Early-Stage Non-Small Cell Lung Cancer

BackgroundOperability is both a crucial determinant in treatment selection and a potential confounder in analyses comparing surgery with non-surgical approaches such as stereotactic body radiotherapy (SBRT). We aimed to assess the association between operability status and intervention with post-treatment mortality in early-stage non-small cell lung cancer (NSCLC).Patients and MethodsWe defined four groups of patients with cT1-T2N0M0 NSCLC diagnosed 2010 to 2014 from the National Cancer Database: SBRT patients deemed operable vs. inoperable and surgery patients receiving open vs. minimally-invasive approaches. Mortality rates at 30, 60, and 90 days post-treatment were calculated and compared.ResultsWe abstracted 80,108 patients, 0.8% undergoing SBRT and operable, 13.2% undergoing SBRT and inoperable, 52.4% undergoing open surgery, and 33.7% undergoing minimally-invasive surgery. Mortality rates were highest among open surgery patients and lowest among operable SBRT patients (2.0% vs. 0.2% at 30 days and 3.7% vs. 0.7% at 90 days), with intermediate results in the other two groups. These findings persisted on multivariate Cox regression: compared to patients undergoing minimally-invasive surgery, mortality risk was highest among open surgery patients (30 days HR 1.32, 95%CI 1.16-1.51; 90 days HR 1.36, 95%CI 1.24-1.50; both P < .001) and lowest among operable SBRT patients (30 days HR 0.09, 95%CI 0.01-0.64; 90 days HR 0.15, 95%CI 0.05-0.46; both P ≤ .016). These associations were maintained in a propensity score-matched subset.ConclusionOperable patients undergoing SBRT experience minimal post-treatment mortality compared to their inoperable counterparts. These findings illustrate the potential for confounding by operability to bias results in cohort studies that compare surgical vs. non-surgical approaches in early-stage NSCLC.     

Meta-Analysis of Neoadjuvant Immunotherapy for Patients with Resectable Non-Small Cell Lung Cancer

Purpose: Immunotherapy has created a paradigm shift in the treatment of metastatic non-small cell lung cancer (NSCLC), overcoming the therapeutic plateau previously achieved by systemic chemotherapy. There is growing interest in the utility of immunotherapy for patients with resectable NSCLC in the neoadjuvant setting. The present systematic review and meta-analysis aim to provide an overview of the existing evidence, with a focus on pathological and radiological response, perioperative clinical outcomes, and long-term survival. Methods: A systematic review was conducted using electronic databases from their dates of inception to August 2021. Pooled data on pathological response, radiological response, and perioperative outcomes were meta-analyzed where possible. Results: Eighteen publications from sixteen studies were identified, involving 548 enrolled patients who underwent neoadjuvant immunotherapy, of whom 507 underwent surgery. Pathologically, 52% achieved a major pathological response, 24% a complete pathological response, and 20% reported a complete pathological response of both the primary lesion as well as the sampled lymph nodes. Radiologically, 84% of patients had stable disease or partial response. Mortality within 30 days was 0.6%, and morbidities were reported according to grade and frequency. Conclusion: The present meta-analysis demonstrated that neoadjuvant immunotherapy was feasible and safe based on perioperative clinical data and completion rates of surgery within their intended timeframe. The pathological response after neoadjuvant immunotherapy was superior to historical data for patients who were treated with neoadjuvant chemotherapy alone, whilst surgical and treatment-related adverse events were comparable. The limitations of the study included the heterogenous treatment regimens, lack of long-term follow-up, variations in the reporting of potential prognostic factors, and potential publication bias.     

Prognostic Significance of the C-erbB-2 Expression in Turkish Non-Small Cell Lung Cancer Patients

Background: The prognostic value of c-erbB-2 expression in patients with non-small cell lung cancer (NSCLC)remains controversial. The prevalence of c-erbB-2 expression in NSCLC and relation to disease prognosis weretherefore investigated. Methods: Eighty-nine patients with NSCLC diagnosed at Baskent University, AdanaHospital, Medical Oncology Department, between 2000-2005 were investigated. Expression of c-erbB-2 wasevaluated by immunohistochemistry in paraffin-embedded sections. Characteristics of patients, histology andstage of the disease were obtained from clinical records. Results: C-erbB-2 expression was detected in 18 patients(20.2%). Median survival of the patients with c-erbB-2 negative was 13 months, as compared to 6 months for cerbB-2 positive cases (p=0.02), the relative risk of death being 1.96 times higher. No correlation was foundbetween c-erbB-2 positivity and stage of the disease or histology of the tumor (p>0.05). Conclusions: C-erbB-2positivity may indicate shorter survival and can be regarded as an unfavorable prognostic factor in NSCLC.Immunohistochemistry seems to be a readily applicable, inexpensive methodology for determining c-erbB-2expression in NSCLCs.     

吉非替尼治疗晚期非小细胞肺癌临床观察

目的 观察吉非替尼作为二线以上的方案治疗晚期非小细胞肺癌的有效性和安全性.方法 本组32例,均经病理学或细胞学检查确诊.其中男18例,女14例,中位年龄62岁,腺癌28例,鳞癌4例,全部患者均接受过2个周期以上的化疗,效果差或不能耐受化疗,均自愿接受吉非替尼单药(250 mg/d)治疗.结果 32例均可评价疗效和毒副反应.治疗2个月后进行评价,CR 1例、PR 11例、SD 14例、PD 6例.RR:37.5%(12/32),DCR 81.25%, TTP 3～26个月,中位TTP 8 个月,MST 10个月.结论 吉非替尼单药二线以上治疗非小细胞肺癌在东方人、女性、腺癌人群中有效率高,耐受性好,可以有效合理地应用分子靶向药物治疗非小细胞肺癌,有效地发挥治疗肿瘤个体化的优势.     

适形放射治疗老年原发性非小细胞肺癌的临床观察

目的 观察适形放射治疗在老年原发性非小细胞肺癌中的治疗效果.方法 对89例年龄≥70岁,KPS≥60的老年原发性非小细胞肺癌进行适形放射治疗,照射剂量为4 000～6 000 cGy,分次剂量400～500 cGy.对有纵隔淋巴结转移的患者先行原发灶、肺门及纵隔常规外照射,剂量为3 000～4 000 cGy.结果 所有患者均完成适形放射治疗,完全缓解(CR)45例,占50.6%,部分缓解(PR)31例,占34.8%,无缓解(NR)11例,占12.4%,总1、2、3年生存率分别是73.0%、41.6%、32.6%.治疗期间发生急性放射性肺炎11例(12.4%),Ⅰ、Ⅱ级放射性食管炎21例(23.6%),经对症支持治疗后均缓解.结论 适形放射治疗是一种提高老年原发性非小细胞肺癌患者生存率和生存质量的有效治疗手段.     

Palliative Systemic Therapy Given near the End of Life for Metastatic Non-Small Cell Lung Cancer

Background: The use of chemotherapy near end of life (EOL) for various cancers is increasing and has been shown to be associated with delayed access to palliative care (PC) and increased aggressiveness in EOL care, without any benefit on survival. Methods: This retrospective study included 90 patients with metastatic non-small cell lung cancer (NSCLC) who received at least one line of palliative systemic anticancer therapy (SACT) and died between 1 November 2014, and 31 October 2016, at Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ). Our primary objective was to evaluate the proportion of patients with NSCLC receiving SACT within 30 days of death. Secondary outcomes were to determine the mean and median delays between the administration of the last treatment and death, and to evaluate if there were differences in characteristics and outcomes (including overall survival (OS)) between patients treated or not within 30 days of death. Results: In our cohort, 22% of patients received SACT within 30 days of death. For the entire cohort, the mean delay between the last treatment and death was 94 days, and the median was 57 days. There were no statistically significant differences between the two groups in terms of baseline characteristics. Use of SACT near EOL was associated with decreased access to PC, higher rates of in hospital death, decreased use of medical aid in dying (MAiD), and a shorter median OS (4.0 vs. 9.0 months). Conclusions: In this retrospective cohort of patients with metastatic NSCLC, 22% of patients received SACT within 30 days of death, with a negative impact on access to PC, higher rates of in hospital death, decreased use of MAiD and palliative sedation, and a shorter median OS.     

Clinicopathologic and Genomic Landscape of Non-Small Cell Lung Cancer Brain Metastases

BackgroundIn patients with non-small cell lung cancer (NSCLC), 10%-40% will eventually develop brain metastases. We present the clinicopathologic, genomic, and biomarker landscape of a large cohort of NSCLC brain metastases (NSCLC-BM) samples.Materials and MethodsWe retrospectively analyzed 3035 NSCLC-BM tested with comprehensive genomic profiling (CGP) during routine clinical care. In addition, we compared the NSCLC-BM to a separate cohort of 7277 primary NSCLC (pNSCLC) specimens. Finally, we present data on 67 paired patients with NSCLC-BM and pNSCLC.ResultsComprehensive genomic profiling analysis of the 3035 NSCLC-BMs found that the most frequent genomic alterations (GAs) were in the TP53, KRAS, CDKN2A, STK11, CDKN2B, EGFR, NKX2-1, RB1, MYC, and KEAP1 genes. In the NSCLC-BM cohort, there were significantly higher rates of several targetable GAs compared with pNSCLC, including ALK fusions, KRAS G12C mutations, and MET amplifications; and decreased frequency of MET exon14 skipping mutations (all P < .05). In the subset of NSCLC-BM (n = 1063) where concurrent PD-L1 immunohistochemistry (IHC) was performed, 54.7% of the patients with NSCLC-BM were eligible for pembrolizumab based on PD-L1 IHC (TPS ≥ 1), and 56.9% were eligible for pembrolizumab based on TMB-High status. In addition, in a series 67 paired pNSCLC and NSCLC-BM samples, 85.1% (57/67) had at least one additional GA discovered in the NSCLC-BM sample when compared with the pNSCLC sample.ConclusionsHerein, we defined the clinicopathologic, genomic, and biomarker landscape of a large cohort of patients with NSCLC-BM which can help inform study design of future clinical studies for patients with NSCLC with BM. In certain clinical situations, metastatic NSCLC brain tissue or cerebral spinal fluid specimens may be needed to fully optimize personalized treatment.     

培美曲塞联合顺铂用于非小细胞肺癌术前新辅助化疗的效果和耐受性

目的 观察培美曲塞(pemetrexed,Alimta)联合顺铂(DDP)用于Ⅲ期非小细胞肺癌(NSCLC)术前新辅助化疗的效果及耐受性.方法 62例Ⅲ期NSCLC手术患者,术前接受新辅助化疗.其中,培美曲塞组28例,接受Alimta +DDP方案,与同期接受诺维苯(NVB)+DDP方案(NP组)34例作比较.结果 培美曲塞组CR 2例,PR 13例,总有效率53.6%;NP组CR 3例,PR 13例,总有效率47.1%,两组有效率比较差异无统计学意义(P>0.05).化疗后肿瘤分期下降两组分别为:培美曲塞组46.4%(13/28),NP组35.3%(12/34),两组比较差异无统计学意义(P>0.05).结论 培美曲塞联合DDP用于NSCLC术前新辅助化疗效果肯定,该方案可作为NSCLC术前新辅助化疗的可选择方案.     

核仁素在胃癌组织芯片中的表达及其意义

目的:探讨核仁素在胃癌组织的表达及其临床意义。方法:采用组织芯片检测胃癌、癌旁良性组织及正常组织中核仁素及细胞核增殖抗原Ki-67的表达。分析胃癌与非癌组织中核仁素的表达定量和定位的差异,统计学分析其与临床病例参数之间的关系及与Ki-67蛋白表达的相关性。结果:胃癌组织和非癌组织中均有核仁素及Ki-67阳性表达于细胞核,但核仁素在胃癌组织的部分细胞的胞膜和/或胞质中亦有阳性表达。核仁素和Ki-67蛋白在胃癌组织阳性表达率明显高于癌旁良性组织及正常组织(P<0.01)。两者在癌旁良性组织及正常组织中的表达无统计学差异。核仁素蛋白在胃癌组织中的表达与肿瘤分化程度、临床病理分期有关(P<0.05)。核仁素与Ki-67的蛋白表达呈显著正相关(P<0.05,r=0.292)。结论:胃癌组织中核仁素的表达增高,检测核仁素的表达可作为临床判断胃癌恶性程度及预后的重要参考指标。     

周剂量多西他赛联合顺铂治疗晚期非小细胞肺癌46例分析

[目的]观察多西他赛每周疗法联合顺铂治疗晚期非小细胞肺癌的近期疗效和毒性反应.[方法]经病理学或细胞学确诊的46例晚期非小细胞肺癌患者给予多西他赛与顺铂联合治疗,其中多西他赛25mg/m2,第1,8,15天静脉滴注1小时,顺铂25mg/m2,第1～3天静脉滴注,28天为一周期,每例患者至少治疗两个周期.[结果]全组46例中,完全缓解(CR)2例,部分缓解(PR)16例,无变化(NC)17例,进展(PD)11例,总有效率(OR)为39.13%.初治组有效率为45.45%,复治组有效率为33.33%,两组差异有显著性(P＜0.05).毒副反应主要为骨髓抑制、消化道反应和脱发.大部分患者为Ⅰ、Ⅱ度反应,耐受良好.骨髓抑制为剂量限制性毒性,其中白细胞减少占65.22%.[结论]多西他赛每周疗法联合顺铂方案治疗晚期非小细胞肺癌具有近期疗效好、毒性反应轻、耐受好.     

NaPi2b expression in a large surgical Non-Small Cell Lung Cancer (NSCLC) cohort

BackgroundNaPi2b is a multi-transmembrane sodium-dependent phosphate transporter expressed at normal levels in several organs, including lung. High expression levels have been reported in various tumors including breast, thyroid, ovarian and non-small cell lung cancer. To date evaluation of NaPi2b expression has mostly been restricted to smaller lung cancer cohorts.MethodsAnalyses were performed on archival formalin fixed paraffin embedded primary tumor specimens from patients who had undergone curative intent resection at an Australian tertiary hospital. Tissue microarrays were constructed and stained with the chimeric anti-NaPi2b antibody, MERS67. Semi-quantitative H-scores (range 0 – 300) were calculated for each core tissue sample (H-score = % tumor cells staining for NaPi2b multiplied by staining intensity). An overall average H-score was reported for each specimen, with a cut-off score of 50 considered positive.ResultsOf 438 cases, high NaPi2b expression was observed in 151 (34.5%) overall, high expression in 137 of 208 (65.9%) adenocarcinoma cases, and 5 of 179 (2.8%) squamous cases (P < .0001). High NaPi2b expression was associated with female sex, EGFR or KRAS mutation, and TTF1 positivity (adenocarcinoma cases only). High NaPi2b expression was associated with improved overall survival (median 54 vs. 35 months, P = .029).ConclusionHigh NaPi2b expression was noted in a significant subset of adenocarcinoma cases, and in particular amongst those who were TTF1+, or exhibited EGFR or KRAS mutations. This agrees with earlier reports and highlights the significance that NaPi2b may have a role as a possible target for delivery of cytotoxic agents via antibody-drug conjugate models for some patients with lung adenocarcinoma.     

Involvement of FoxM1 in Non-Small Cell Lung Cancer Recurrence

Background: Predictive biomarkers for lung cancer recurrence after curative tumor resection remainunclear. This study set out to assess the role of FoxM1 in the recurrence of non-small cell lung cancer. Methods:Immunohistochemistry for FoxM1 expression was performed on paraffin-embedded tumor tissues from 165NSCLC patients. Association of FoxM1 expression with clinicopathological parameters and disease free survivalwere evaluated. Results: Our results indicated FoxM1 expression to be significantly associated with poorer tissuedifferentiation (P =0.03), higher TNM stage (P <0.01), lymph node metastasis (P <0.01), advanced tumor stage(P <0.01), and poorer disease free survival (P <0.01). Multivariable analysis showed that FoxM1 expressionincreased the hazard of recurrence (hazard ratio= 1.96, 95% CI, 1.04-3.17, P <0.05), indicating that FoxM1is an independent and significant predictor of lung cancer recurrence. Conclusion: Therefore, FoxM1 is anindependent risk factor for recurrence of NSCLC. Elevated FoxM1 expression could be used as an indicator ofpoor disease free survival.     

晚期非小细胞肺癌60例化疗疗效影响因素探讨

目的探讨影响晚期非小细胞肺癌化疗疗效的因素。方法分析60例晚期非小细胞肺癌的病例资料;比较3种不同化疗方案的疗效;采用χ2检验比较各因素对化疗疗效的影响。结果3种化疗方案疗效无显著性差异;7个影响因素中,性别、PS评分、临床分期、既往治疗情况和转移部位5个因素对晚期NSCLC患者化疗疗效有显著影响。结论可通过改善行为状态来提高化疗效果。     

Management of Elderly Patients with Advanced Non-Small Cell Lung Cancer in Turkey

Objective: Non-small cell lung cancer is a disease that affects the elderly. However, most patients older than70 years are less likely to receive standard therapy than their younger counterparts and the aim of the presentstudy was to determine age-dependent variation in efficacy. Subjects and Methods: Between 2004-2008, 40consecutive patients older than 70 years received treatment for advanced non-small cell lung cancer. All wereevaluated for response and toxicity. Chemotherapy was either with cisplatin or carboplatin and double or singleagents (vinorelbine, gemcitabine). Docetaxel was used as a second line therapy in selected cases. Patients weregrouped according to age: group 1 (70-74 years), group 2 (≥ 75 years). Results: Except for 4 cases, all receivedchemotherapy, and 61 % were given a cisplatin-containing regimen. Second-line therapy was given to 42.5%and grades 3-4 neutropenia was seen in 17 (42.5%). Only one patient died due to neutropenic fever. Nephrotoxicitywas observed in 2 (5%) and one underwent hemodialysis. Overall survival was 10 months, with median survivalperiods for groups 1 and 2 of 13 and 10 months, respectively (p>.05). No differences were found regarding typeof chemotherapy administered or adverse events between the 2 groups. Conclusion: Patients older than 75years appear to deserve the same standard therapy for non-small cell lung cancer as that given to younger cases.     

人乳头瘤病毒感染与梅州地区非小细胞肺癌发生的关系

目的 探讨人乳头瘤病毒( HPV)感染与梅州地区非小细胞肺癌(NSCLC)发生的关系.方法应用免疫组织化学SABC法检测43例NSCLC和27例肺良性病变组织中HPV的表达情况.结果HPV在NSCLC和肺良性病变组织中的检出率分别为39.5%和7.4%,差异有统计学意义(P=0.003).结论HPV感染与梅州地区NSC...     

ADMV方案治疗中晚期非小细胞肺癌62例近期疗效分析

采用ＡＤＭＶ（ＡＤＭ＋ＤＤＰ＋ＭＭＣ＋ＭＭＣ＋ＶＰ－１６）方案联合化疗，对６２例中晚期非小细胞肺癌近期疗效观察，ＣＲ２例，ＰＲ１８例，ＮＲ３２例，ＰＤ１０例，总有效率（ＣＲ＋ＰＲ）３２．２６％（２０／６２）。化疗毒副反应主要是消化道反应（５９．６８％）及骨髓抑制（白细胞下降占６１．２９％）。