长春瑞滨联合放射治疗非小细胞肺癌

放化疗联合治疗局限晚期非小细胞肺癌已取得较大的成功,但仍存在一些问题亟待解决。近年,同步化放疗日益受到关注,其策略思路是强化局部病灶控制的同时,兼顾全身转移微小病灶的治疗。     

长春瑞滨联合放射治疗非小细胞肺癌

放化疗联合治疗局限晚期非小细胞肺癌已取得较大的成功,但仍存在一些问题亟待解决。近年,同步化放疗日益受到关注,其策略思路是强化局部病灶控制的同时,兼顾全身转移微小病灶的治疗。     

Functional image-based radiotherapy planning for non-small cell lung cancer: A simulation study

Background and purpose

To investigate the incorporation of data from single-photon emission computed tomography (SPECT) or hyperpolarized helium-3 magnetic resonance imaging (³He-MRI) into intensity-modulated radiotherapy (IMRT) planning for non-small cell lung cancer (NSCLC).

Material and methods

Seven scenarios were simulated that represent cases of NSCLC with significant functional lung defects. Two independent IMRT plans were produced for each scenario; one to minimise total lung volume receiving ?20 Gy (V₂₀), and the other to minimise only the functional lung volume receiving ?20 Gy (FV₂₀). Dose-volume characteristics and a plan quality index related to planning target volume coverage by the 95% isodose (V_PTV95/FV₂₀) were compared between anatomical and functional plans using the Wilcoxon signed ranks test.

Results

Compared to anatomical IMRT plans, functional planning reduced FV₂₀ (median 2.7%, range 0.6-3.5%, p = 0.02), and total lung V₂₀ (median 1.5%, 0.5-2.7%, p = 0.02), with a small reduction in mean functional lung dose (median 0.4 Gy, 0-0.7 Gy, p = 0.03). There were no significant differences in target volume coverage or organ-at-risk doses. Plan quality index was improved for functional plans (median increase 1.4, range 0-11.8, p = 0.02).

Conclusions

Statistically significant reductions in FV₂₀, V₂₀ and mean functional lung dose are possible when IMRT planning is supplemented by functional information derived from SPECT or ³He-MRI.     

Swedish lung cancer radiation study group: predictive value of histology for radiotherapy response in patients with non-small cell lung cancer

The aim of the present study was to evaluate the potential predictive value of histology in non-small cell lung cancer (NSCLC) treated with curatively intended radiotherapy. In a collaborative effort among all the Swedish Oncology Departments, clinical data were collected for 1146 patients with a diagnosed non-small cell lung cancer subjected to curatively intended irradiation (?50 Gy) during the years 1990 to 2000. The included patients were identified based on a manual search of all medical and radiation charts at the oncology departments from which the individual patient data were collected. Only patients who did not have a histological diagnosis date and death date/last follow-up date were excluded (n = 141). Among the 1146 patients with non-small cell carcinoma eligible for analysis, 919 were diagnosed with either adenocarcinoma (n = 323) or squamous cell carcinoma (n = 596) and included in this study. The median survival for the 919 patients was 14.8 months, while the 5-year survival rate was 9.5%. Patients with adenocarcinoma had a significantly better overall survival compared with patients with squamous cell carcinoma (p = 0.0062, log-rank test). When comparing different stages, this survival benefit was most pronounced for stages IIA–IIB (p < 0.0001, log-rank test). The difference in survival between the two histological groups was statistically significant in a univariate Cox analysis (p = 0.0063) as well as in two multivariate Cox analyses including demographic and treatment variables (p = 0.037 and p = 0.048, respectively). In this large population based retrospective study we describe for the first time that patients with adenocarcinoma have a better survival after curatively intended radiation therapy in comparison with squamous cell carcinoma patients, particularly those with clinical stages IIA–IIB.     

Four-dimensional stereotactic radiotherapy for early stage non-small cell lung cancer: a comparative planning study

In this study we sought to assess the potential of the respiratory tumor tracking system of the CyberKnife to administer 3 fractions of 15 Gy in the treatment of early stage non-small cell lung cancer (NSCLC). The CyberKnife plans were compared to those developed for 3-D conformal radiotherapy (3-D CRT) administering 20 fractions of 3 Gy based on a slow CT. Ten patients with stage I NSCLC, who were previously treated with 3-D CRT, were re-planned with the CyberKnife treatment planning system. In the 3-D CRT plan, the planning target volume (PTV) included the gross tumor volume (GTV)(slow) and a 15-mm margin, whereas in the CyberKnife plan the margin was 8 mm. The physical doses from both treatment plans were converted to normalized total doses (NTD) using the linear quadratic model with an alpha/beta(tumor) of 10 Gy and alpha/beta(organs at risk (OAR)) of 3 Gy. The average minimal and mean doses administered to the PTV with the CyberKnife and 3-D CRT were 93 and 115.8 Gy and 61 and 66 Gy, respectively (p<0.0001). The mean V(20) of the CyberKnife and 3-D CRT plans were 8.2% and 6.8%, respectively (p=0.124). Both plans complied with the OAR constraints. In conclusion, 4-dimensional stereotactic radiotherapy can increase the minimal and mean biological dose with 51% and 75%, in comparison with 3-D CRT without significantly increasing the V(20), respectively.     

COAPC方案联合脑部放射治疗非小细胞肺癌脑转移

背景与目的：放射治疗具有治疗脑转移癌的主要手段。而到目前为止化疗与放疗联合治疗脑转移癌的研究较少,本研究旨在观察COAPC方案化疗与脑部放射同时治疗非小细胞肺癌（non-small cell lung cancer,NSCLC)脑转移患者疗效,不良反应及生存率。方法：45例NSCLC脑转移患者接受COAPC方案化疗,环磷酰胺0．3g/m^2第1天静推,长春新碱1．4mg/m^2第1天静推,阿霉素50mg/m^2第1天静推,顺铂20mg/m^2第1－5天静滴,司莫司汀80mg/m2第1天口服,每3－4周为1疗程,脑部放射治疗于化疗第1疗程的第6天开始,每次2Gy,每天1次,每周5天,脑转移灶1－3个者,全脑放疗40Gy后,缩野放疗至总量60Gy,脑转移灶＞3个者,全脑放疗至总量40Gy.结果：治疗后80％患者神经系统症状改善,对脑转移灶的客观有效率为64．4％,对肺原发灶的有效率为40％,治疗的主要不良反应为骨髓抑制(Ⅲ-Ⅳ度占35％）,中位生存期10个月,1年生存率44．1％,5年生存率6．7％,单纯脑转移患者的中位生存期14个月,高于多发远处转移患者的9个月（P＝0．012）。结论：化疗联合脑部放射治疗NSCLC脑转移患者有效率与生存率较高,且患者耐受性较好。     

非小细胞肺癌自适应放疗剂量学研究

  目的  探索非小细胞肺癌实施自适应放疗后危及器官(肺、心脏、脊髓)受照剂量的变化, 及危及器官受照剂量降低后靶区处方剂量的变化。  方法  12例局部晚期非小细胞肺癌患者在放疗过程中均行两次定位CT扫描, 以实行自适应放疗。通过MIM软件, 将两次计划进行融合。比较实行自适应放疗后, 保证靶区剂量不变的情况下, 危及器官的受量有无降低; 以及在保证正常组织器官受照剂量与原计划相似的情况下靶区剂量提升的空间。  结果  自适应放疗后, 在保证靶区受照剂量不变的情况下, 肺部V20平均降低3.53%, V30降低2.55%, 而全肺平均受照剂量降低2.11 Gy; 心脏V30平均降低4.19%、V40降低3.72%;脊髓最大受量平均降低3.52 Gy。危及器官受量与不行自适应放疗时相似的情况下, 靶区(PGTV)照射剂量平均提高1.25 Gy。  结论  非小细胞肺癌放疗过程中, 适时行自适应放疗能够减少周围危及器官的受照剂量, 提高靶区(PGTV)的处方剂量。      

High dose rate brachytherapy in patients with local recurrences after radiotherapy of non-small cell lung cancer.

Thirty-one patients with recurrences of locally advanced Stage III lung cancer were treated with high dose rate brachytherapy. All patients had previously received a full course external beam irradiation. All treatments were performed under topical anaesthesia and took 6-14 min depending on the strength of the Iridium-192 source. The high dose rate brachytherapy was calculated as 10 Gy at one cm from the source axis for each session and this was repeated every 2 weeks to a maximum of three sessions. All treatments were well tolerated and no immediate treatment related complications were observed. Response evaluation 6 weeks after high dose rate brachytherapy showed that there was a partial response in 22 patients and nine patients were non-responders. Median survival was 7 and 3 months, respectively. All non-responders had initially presented with a T4N3 tumor. Ten patients died because of fatal pulmonary hemorrhages 2-24 weeks after brachytherapy and three others died because of a bronchial fistula. Endobronchial brachytherapy appears to be a valuable treatment alternative for local palliation. However, the relatively high number of complications at follow-up warrants further investigation to establish the optimal benefit to be derived from high dose rate brachytherapy treatment of locally advanced Stage III tumors.     

非小细胞肺癌胸部放疗联合免疫治疗研究进展

非小细胞肺癌(NSCLC)放疗联合免疫治疗,特别是联合PD-1/PD-L1免疫检查点抑制剂治疗,已成为近年来的研究焦点。探索放疗与免疫治疗的最优空间组合模式,实现各期患者最大限度的获益,是目前临床研究的方向之一。本文对放疗对肿瘤免疫环境的影响、各期NSCLC放疗联合免疫治疗进展以及存在的问题进行综述。     

不同剂量算法在非小细胞肺癌立体定向放射治疗计划中的比较北大核心

目的:比较Acuros XB和AAA两种剂量算法在非小细胞肺癌立体定向放射治疗计划中的差异。方法:研究选取14例肺部非小细胞肺癌病例治疗计划,分别采用Acuros XB、AAA算法进行剂量计算,对比不同剂量算法对患者剂量的影响。结果:在低密度组织中,如靶区D_(max)、D_(mean)及肺V_(5)、D_(mean)参数,Acuros XB算法结果高于AAA算法。实质性器官脊髓D_(mean)、心脏D_(mean)结果,Acuros XB算法低于AAA算法。在胸部双弧计划中Acuros XB算法较AAA算法运算用时缩短约59.5%。结论:对于胸部非小细胞肺癌立体定向计划,建议采用更快、更准的Acuros XB算法。     

Acute esophageal toxicity in non-small cell lung cancer patients after high dose conformal radiotherapy.

BACKGROUND AND PURPOSE: To correlate acute esophageal toxicity with dosimetric and clinical parameters for non-small cell lung cancer (NSCLC) patients treated with radiotherapy (RT) alone or with chemo-radiotherapy (CRT). PATIENTS AND METHODS: We analyzed the data of 156 patients with medically inoperable or locally advanced NSCLC. Seventy-four patients were irradiated with high dose RT only, 45 patients with sequential CRT (Gemicitabine/Cisplatin) and 37 patients with concurrent CRT (Cisplatin daily 6 mg/m(2)). The radiation dose delivered ranged from 49.5 to 94.5 Gy (2.25-2.75 Gy per fraction) with an overall treatment time of 5-6 weeks. For all patients the maximal acute esophageal toxicity (RTOG/EORTC criteria) was scored and related to dose-volume parameters, as well as to clinical and treatment-related parameters. All parameters were tested univariable and multivariable in a binary logistic regression model. The toxicity data of a homogeneous subgroup was fitted to the Lyman-Kutcher-Burman model. RESULTS: Grade 2 acute esophageal toxicity or higher occurred in 27% (n=42) of the patient population of which nine patients developed grade 3 toxicity and one patient grade 4. All 10 patients with grade>or=3 esophageal toxicity received concurrent CRT. At multivariable analysis, the most significant clinical parameter to predict acute esophageal toxicity was the concurrent use of CRT. The most significant dosimetric parameter was the esophagus volume that received at least 35 Gy. The data of the patients who did not receive concurrent CRT were well described by the Lyman-Kutcher-Burman normal tissue complication probability model. The optimal fit of the data of non-concurrent treated patients to this model was obtained using the following values for the parameters: TD(50)=47 Gy (41-60 Gy), n=0.69 (0.18-6.3) and m=0.36 (0.25-0.55) where the numbers between brackets denote the 95% confidence interval. Acute esophageal toxicity was not significantly increased for patients treated with sequential CRT. CONCLUSION: Both concurrent CRT and the volume that receives at least 35 Gy were predictors of acute esophageal toxicity.     

DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients.

We used MethyLight assays to analyze DNA methylation status of 27 genes on 49 paired cancerous and noncancerous tissue samples from non-small cell lung cancer (NSCLC) patients who underwent surgical resection. Seven genes (RARB, BVES, CDKN2A, KCNH5, RASSF1, CDH13, and RUNX) were found to be methylated significantly more frequently in tumor tissues than in noncancerous tissues. Only methylation of CCND2 and APC was frequently detected in both cancerous and noncancerous tissues, supporting the hypothesis that the methylation of these two genes is a preneoplastic change and may be associated with tobacco smoking exposure. Methylation of any one of eight genes (RASSF1, DAPK1, BVES, CDH13, MGMT, KCNH5, RARB, or CDH1) was present in 80% of NSCLC tissues but only in 14% of noncancerous tissues. Detection of methylation of these genes in blood might have utility in monitoring and detecting tumor recurrence in early-stage NSCLC after curative surgical resection.     

常规放疗配合三维适形照射治疗非小细胞肺癌——附120例分析

目的:观察常规放疗配合三维适形照射对非小细胞肺癌的治疗结果。方法:收集我科治疗的ⅡB和Ⅲ期非小细胞肺癌患者120例。常规结合三维适形放疗(综合)组50例先常规照射30Gy,再行三维适形放疗30Gy,三维适形放疗分割剂量5~6Gy/次,3次/周。单纯常规放疗(常规)组70例,设前后两野照射40Gy,再对残存病灶放疗30Gy。结果:综合和常规组总的肿瘤消退率分别为94·4%和96%,完全消退率综合组为40%,而常规仅为21·4%。随访结果,综合组和常规组的1、3和5年生存率分别为84%、52%、26%和66%、40%、15%,差异无统计学意义,P>0·05。结论:三维适形配合常规放射治疗局部中晚期非小细胞肺癌有较好的近期疗效,对生存率的影响不明显。     

周剂量紫杉醇同步放疗治疗26例晚期非小细胞肺癌的临床观察

目的：观察周剂量紫杉醇同步放疗治疗晚期非小细胞肺癌（NSCLC）的疗效及不良反应。方法：26例患者均为不能手术切除的Ⅲ～Ⅳ期NSCLC，采用周剂量紫杉醇全身化疗，同步应用直线加速器三维适形外照射放疗。结果：26例均可评价疗效，完全缓解（CR）3例，部分缓解（PR）15例，无变化（NC）6例，恶化（PD）2例，总有效率（CR＋PR）69．2％；中位疾病进展时间（mTTP）为8．0个月（95％CI：6．0～12．0个月），中位生存时间（MST）10．0个月（95％CI：6．0～16．5个月）。不良反应较轻。结论：周剂量紫杉醇同步三维适形放疗是不能手术切除的中晚期NSCLC的有效治疗方法之一。     

三维适形放疗联合多西紫杉醇同期化疗治疗老年局部晚期非小细胞肺癌临床研究

目的:研究三维适形放射治疗联合多西紫杉醇同期化疗治疗老年局部晚期非小细胞肺癌疗效和不良反应.方法:84例局部晚期非小细胞肺癌患者随机分成A组和B组,A组40例采用三维适形放射治疗,总剂量66-70Gy/33-35次,6-7周完成.B组44例采用三维适形放射治疗联合多西紫杉醇同期化疗.结果:两组患者的总有效率分别为57.9%和80.5%,其中CR率分别为7.9%和29.3%,P＜0.05.两组1、2年生存率分别65.7% vs 80.5%和 39.5% vs 53.7%( P＞0.05).A组患者中位生存期为10.5个月,B组患者为19.5个月.两组患者早期放射反应主要为I-II级放射性食道炎和骨髓抑制,后期放射反应主要为I-II级放射性肺炎,发生率两组接近.结论:三维适形放射治疗联合多西紫杉醇同期化疗治疗局部晚期非小细胞肺癌疗效优于单纯三维适形放射治疗.     

放疗联合EGFR-TKIs 治疗非小细胞肺癌新进展

在全球范围内,肺癌是造成癌症死亡的最主要原因。非小细胞肺癌（non-small cell lung cancer ,NSCLC ）约占肺癌的80% ,由于缺乏早期诊断的有效手段,临床上首诊NSCLC 患者仅25% ～30% 可选择根治性手术。对于不能手术切除的局部晚期及晚期NSCLC ,单纯放射治疗或放化疗综合治疗是主要治疗手段,但总体疗效并不理想。近年来,靶向药物开创了 NSCLC 个体化治疗时代,越来越多的证据提示以表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors ,EG?FR-TKIs）为代表的靶向药物联合放疗或放化疗治疗NSCLC 具有一定的前景。本文就EGFR-TKIs 联合放疗治疗不可手术的局部晚期及晚期NSCLC 的新进展做一综述。     

吉非替尼联合放疗治疗晚期非小细胞肺癌的研究进展

研究证实吉非替尼治疗表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者疗效明确,并具有放疗增敏效果。国内外诸多研究表明吉非替尼联合放疗能显著提高患者生存时间,特别是对高龄患者或脑转移患者,且不良反应较小,患者生命质量较高。因此,吉非替尼联合放疗将成为治疗晚期 NSCLC 患者的有效治疗手段。