肺癌三维适形及调强放疗诱导肺损伤与剂量体积直方图参数的相关性

目的 探讨肺癌三维适形放疗（3D-CRT）和调强放疗（IMRT）诱导肺损伤（RILI）与剂量体积直方图（DVH）参数的关系及两种放疗计划的差异。方法 151例肺癌患者分别接受3D-CRT（n=90）和IMRT（n=61）,均给予根治性放疗剂量,采用传统分割照射（1.8～2.0Gy／次,1次／天,5次／周）,中位剂量60.0Gy。比较两组发生RILI的差异,并分析两组发生≥2级RILI与DVH参数的关系。结果 3D-CRT组≥2级RILI发生率为17.8％,略低于IMRT组的24.6％;≥3级RILI发生率为8.9％,略高于IMRT组的3.3％,差异无统计学意义（P＞0.05）。单因素分析显示,3D-CRT组V20可增加≥2级RILI的发生风险（OR=3.780,P=0.030）;IMRT组V5、V10、V13、V20和平均照射剂量均可增加≥2级RILI的发生风险（OR：3.575～6.286,P：0.003～0.045）。多因素分析显示V20是RILI的独立危险因素。结论 3D-CRT和IMRT对肺癌患者≥2级RILI的发生率影响不明显,但RILI的发生风险均与V20相关。     

非小细胞肺癌术后放疗相关肺毒性风险因素分析

目的 评估手术后接受现代放疗技术的非小细胞肺癌(NSCLC)患者术后有症状的放射性肺毒性(SRILT)发生率及风险因素。方法 回顾性分析2002-2011年于中国医学科学院肿瘤医院行手术治疗且接受术后三维适形或调强放疗的NSCLC患者。采用不良反应评价标准3.0版进行放疗相关肺毒性分级,≥2级定义为SRILT。Logistic回归模型评估潜在的临床因素和剂量学因素。结果 227例患者入组,包括190例肺叶切除术和37例全肺切除术者。23例(10.1%)患者发生了SRILT,均为肺叶切除术后放疗者。放射性肺炎2级17例、3级5例、4级1例。单因素分析结果显示术后同步放化疗、较大的PTV、平均肺剂量、V20-V40与SRILT发生率相关(P=0.015、0.048、<0.001),多因素分析结果显示术后同步放化疗、V20与SRILT发生相关(P=0.017、0.009)。结论 NSCLC术后放疗后SRILT发生率较低,同步放化疗及V20为SRILT发生的影响因素。     

Local failure in patients treated with radiotherapy and multidrug chemotherapy for small cell lung cancer

Fifty-three patients with small cell carcinoma of the lung were treated with chemotherapy and radiotherapy, 40 Gy in the chest tumour. Intrathoracic failure occurred in 89% of the cases with extensive disease and in 60% of those with limited disease. Since 86% of all failures were localized within the target volume, one can conclude that in most cases the radiation dose was too low for eradication of the tumour. The treatment technique resulted in dose inhomogeneities of more than +/- 5% in 45% of the cases. The high local failure rate might indicate the need of improved radiotherapy, in the first place higher radiation dose. However, 82% of the patients with limited disease and local failure and 50% of those without local failure also developed distant metastases. This might indicate that the curative potential of improved thoracic radiotherapy probably is limited. Besides, lethal treatment toxicity affected particularly patients in whom local cure had been achieved, indicating the difficulty of increasing the treatment intensity without increasing the lethal toxicity in potentially curable cases.     

非小细胞肺癌放疗后有症状放射性肺损伤临床特点分析

目的 分析非小细胞肺癌(NSCLC)患者放疗后发生有症状放射性肺损伤(SRILI)的临床特点。方法 回顾分析2000—2007年放疗的NSCLC患者治疗期间或随访中发生并在本院治疗的SRILI临床症状、体征、影像及血液学改变等。SRILI经2名放疗科和1名影像科医生根据不良反应常见术语标准3.0版进行诊断和分级。结果 81例SRILI患者纳入分析,其中2级 35例、3级 42例、4级 0例、5级 4例。自放疗开始SRILI症状出现时间中位数8.3周。SRILI症状主要为咳嗽(95%)、气短(69%)、发热(48%),最高体温中位数38.3℃。临床体征相对较少,常见为呼吸音粗糙(50%)。影像表现为放射野内肺实变、通气支气管征、斑片和条索影,少数出现在放射野外。血象改变为中性粒细胞比例稍高(中位数77.4%)。结论 SRILI出现在放疗开始后平均8.3周,临床特点表现为咳嗽、气短、发热、呼吸音粗糙,放射野内或少数野外实变、斑片、条索影,中性粒细胞比例稍高。     

非小细胞肺癌三维适形放疗放射性肺损伤临床及剂量学因素分析

目的 探讨非小细胞肺癌(NSCLC)根治性三维适形放疗(3DCRT)后放射性肺损伤发生因素.方法 搜集86例接受根治性3DCRT[处方剂量≥60～66 Gy,1.8～2.0 Gy/(次·d),5 d/周]的NSCLC患者资料,对性别、年龄、吸烟史、心脏病史、肺功能、发病部位、临床分期、病理诊断、是否合并化疗等临床因素以及放疗剂量、射野数量、平均肺受量(MLD)、正常肺体积剂量(V_5～V_(65)间隔5 Gy)等剂量学因素与放射性肺损伤之间的关系进行回顾性分析.采用CTC 3.0标准对放射性肺损伤进行分级,单因素及多因素分析筛选预测因素.结果 中位随访期12个月(1～36个月),12例发生≥3级放射性肺损伤.单因素分析V_5～V_(35)MLD等因素与放射性肺损伤有关,而与全部临床因素、放疗剂量、照射野数、V_(40)～V_(65)等无关.筛选单因素分析中有统计学意义的因素进行Logistic回归分析,结果仅V_5是放射性肺损伤发生的独立预后因素(χ~2=5.15,P=0.023).V_5≤45%组放射性肺损伤发病率为2%,V_5>45%组为26%(χ~2=10.24,P=0.001).结论 受照体积可能比受照剂量对放射性肺损伤发生的影响更大.众多剂量学因素与放射性肺损伤发生相关,其中V_5是独立预后因素.     

非小细胞肺癌三维适形放疗剂量体积直方图参数与放射性肺损伤CT分级的关系

目的 探讨剂量体积直方图(DVH)参数与非小细胞肺癌(NSCLC)三维适形放疗(3D-CRT)后放射性肺损伤CT分级的关系.方法 将3D-CRT治疗后CT随访6个月以上的169例Ⅰ～Ⅲ期NSCLC患者,按随访CT放射性肺损伤的表现分级(0～4级),并分为CT阳性组(2～4级)和CT阴性组(0～1级).从放疗计划中获取患者的DVH参数,分析DVH参数与放射性肺损伤CT分级的关系,评价DVH参数对放射性肺损伤的预测价值.结果 不同CT分级的全肺及患侧肺正常组织并发症概率(NTCP)值差异有统计学意义,随着CT分级的增加,NTCP相应增大.不同CT分级的全肺及患侧肺平均肺受照剂量(MLD)差异有统计学意义,随着CT分级的增加,全肺及患侧肺MLD相应增大.不同CT分级的全肺及患侧肺V20、V30和V40差异均有统计学意义,随着CT分级的增加,全肺及患侧肺V20、V30、V40相应增大.不同CT分级患者健侧肺的DVH参数差异无统计学意义.全肺、患侧肺DVH参数与患侧肺CT分级联系紧密,其中患侧肺NTCP与CT分级关联度最强(η=0.522).结论 NTCP、MID、V20、V30、V40等DVH参数与NSCLC 3D-CRT后放射性肺损伤的CT分级密切相关,可以作为评价及优化放疗计划的指标,以减少放疗后放射性肺损伤的发生.     

肺癌放疗所致放射性肺损伤的相关因素分析

目的:分析肺癌三维适形放疗中与放射性肺损伤相关的各种因素,并探讨预测价值。方法:对70例接受三维适形放疗的非小细胞肺癌患者根据是否发生放射性肺损伤进行回顾性对照研究,将放射性肺损伤相关临床因素大致分为患者一般情况与系统病变、肿瘤自身因素、放疗除外其他治疗和放疗相关因素4类,并进行单因素和多因素分析。结果:单因素分析显示:仅大体肿瘤体积(P=0.009)和部分剂量体积参数如患者平均肺受量(P=0.017)、患肺V20(P=0.036)和全肺平均肺受量(P=0.034)对放射性肺损伤有显著影响,而其他因素影响不显著。多因素分析显示:剂量体积参数中仅平均肺受量(P=0.019)为放射性肺损伤独立相关因素。结论:参考剂量体积参数和大体肿瘤体积有助于预测放射性肺损伤的发生。     

广泛期SCLC化疗后IMRT的疗效分析

目的 回顾研究广泛期SCLC化疗后IMRT的疗效及预后。方法 回顾分析2007—2012年在本院放疗科接受化疗+IMRT的130例初治广泛期SCLC患者,化疗方案以EP、CE方案为主,放疗剂量32 Gy~63 Gy,35例患者进行了PCI。Kaplan-Meier法计算生存率,Logrank法单因素预后分析,Cox模型多因素预后分析。结果 随访率96.1%。全组治疗毒性轻微,≥2级血液学毒性及放射性食管炎发生率分别为22.3%、12.2%,≥2级RP发生率7.7%。放疗后达CR、PR、SD、PD者分别占4.6%、72.3%、6.2%、13.1%,疗效未能评价5例,客观有效率76.9%。中位生存期18个月(4~66个月),1、2年OS率分别为72.3% 、38.3%。30例(23.1%)患者放疗后发生局部区域失败,83例(63.8%)发生远处失败。26例放疗计划可恢复的局部区域失败患者中,22例单纯照射野内失败,2例单纯野外失败,2例野内野外同时失败。单因素分析中年龄、LDH水平、放疗剂量、PCI是影响预后因素(P=0.014、0.049、0.043、0.003),多因素分析中放疗剂量、PCI是影响预后因素(P=0.021、0.007)。初诊无脑转移患者PCI明显改善生存(HR=2.318,95%CI为1.388~3.871;P=0.003)并降低累积脑转移率(18.4%:37.2%,P=0.038)。胸部放疗EQD₂剂量达54 Gy可改善OS (HR=1.615,95%CI为1.016~2.567;P=0.043),并有改善PFS趋势(HR=1.49,95%CI为0.965~2.299,P=0.072)。结论 化疗有效的广泛期SCLC行胸部放疗可提高LC率及OS率,适当提高胸部剂量可改善患者预后。PCI可显著改善OS并降低脑转移发生率。     

256例局部晚期NSCLC调强放疗后放射性肺损伤预测因素分析

目的 探讨局部晚期NSCLC受累野IMRT后放射性肺损伤发生率及寻找预测因素。方法 2007—2011年间在我院治疗的256例未手术、Ⅲ期NSCLC患者。放疗采用受累野IMRT。放疗剂量50~70 Gy (中位值60 Gy),分割剂量2 Gy/次。109例(42.6%)接受同期化疗。采用NCI的CTCAE 3.0标准评估级别。以放疗结束后6个月内发生≥2级放射性肺损伤作为终点事件。采用Logistic回归模型对预测因素进行分析。结果 所有患者中男215例(84%)、女41例(16%)。诊断时平均年龄59.2岁。43例(16.7%)发生≥2级放射性肺损伤。出现放射性肺损伤时间距放疗开始时间为20~169 d (中位数64 d)。单因素分析显示吸烟、肿瘤位置、双肺平均剂量、双肺V₅—V₂₀与≥2级放射性肺损伤发生可疑相关(P=0.108、0.106、0.030、0.049),多因素分析结果显示双肺平均剂量和双肺V₅—V₂₀与≥2级放射性肺损伤发生密切相关(P=0.048)。结论 局部晚期NSCLC受累野IMRT后双肺平均剂量和DVH中低剂量区体积可以初步预测症状性放射性肺损伤发生。     

Evaluation of infections in non-small cell lung cancer patients treated with radiotherapy

PURPOSE: We aim to determine infections occurring in patients with non-small cell lung cancer during radiotherapy (RT). METHODS AND MATERIALS: A total of 181 patients had been treated with thoracic radiotherapy between October 1995 and December 1999. Radiotherapy was given using 1.8-3Gray (Gy) fraction daily, five fractions a week for a total dose of 59.4Gy (30-70.2Gy). A complete history was collected retrospectively for each patient. All microbiological examinations were performed according to the routine procedures of the hospital laboratory. Numeric and categoric variables were employed such as sex, age, performance status, histology, stage, chemotherapy, usage of corticosteroids, neutropenia, surgery, hospitalization, associated diseases, smoking during treatment, package per year of cigarette smoking, dose of radiotherapy, and response rates. RESULTS: Infections developed in 84 patients (46%, 84/181) during thoracic radiotherapy. A 101 episodes of infections developed in these patients. Most patients suffered from sputum production (65%), cough (59%), auscultation findings (31%) and fever (31%). Gram-negative bacteria were the most frequently isolated pathogens in the cultures of specimens (70%, 16/23 samples). Neoadjuvant chemotherapy (OR=4.81; 95% CI, 1.57-9.12; p=0.003) and neutropenia (OR=4.25; 95% CI, 1.44-6.89; p=0.009) were found as risk factors for influencing infection based on logistic regression analyses. Package per year of cigarette smoking was found statistically significantly higher in patients with infections than patients without infections (p=0.001). A slight increase in infections, which was of borderline statistical significance (p=0.07), was observed in patients age over 70. Ciprofloxacin and clarithromycin were the most frequently used agents in treatment. Median survival was 9 months in the patients with infection and 13 months in the 97 patients without infection. Overall survival seemed to be statistically significantly better in patients without infection than patients with infection (p=0.042) calculated using Kaplan-Meier method. Based on Cox regression analyses; overall survival was not correlated to presence of infection but associated with poor performance status (5940 cGy (OR=2.06; 95% CI, 0.72-7.18; p=0.007) and the absence of response to treatment (OR=2.45; 95% CI, 0.89-14.23; p<0.001) were also found to be risk factors for survival. CONCLUSIONS: Infections are important causes of morbidity and mortality in lung cancer patients. The control of infection in these patients may improve the survival. Predisposing factors and treatment management approaches in non-small cell lung cancer should be defined carefully.     

Accelerated hyperfractionated radiotherapy and concomitant chemotherapy in small cell lung cancer limited-disease. Dose response, feasibility and outcome for patients treated in western Sweden, 1998-2004

Addition of thoracic radiation therapy (TRT) to chemotherapy (CHT) can increase overall survival in patients with small cell lung cancer limited-disease (SCLC-LD). Accelerated fractionation and early concurrent platinum-based CHT, in combination with prophylactic cranial irradiation, represent up-front treatment for this group of patients. Optimised and tailored local and systemic treatment is important. These concepts were applied when a new regional treatment programme was designed at Sahlgrenska University Hospital in 1997. The planned treatment consisted of six courses of CHT (carboplatin/etoposide)+TRT±prophylactic cranial irradiation (PCI). Standard TRT was prescribed as 1.5 Gy BID to a total of 60 Gy during 4 weeks, starting concomitantly with the second or third course of CHT. However, patients with large tumour burdens, poor general condition and/or poor lung function received 45 Gy, 1.5 Gy BID, during 3 weeks. PCI in 15 fractions to a total dose of 30 Gy was administered to all patients with complete remission (CR) and “good” partial remission (PR) at response evaluation.

Eighty consecutive patients were treated between January 1998 and December 2004. Forty-six patients were given 60 Gy and 34 patients 45 Gy. Acute toxicity occurred as esophagitis grade III (RTOG/EORTC) in 16% and as pneumonitis grade I-II in10%. There were no differences in toxicity between the two groups. Three- and five-year overall survival was 25% and 16%, respectively. Median survival was 20.8 months with no significant difference between the two groups. In conclusion, TRT with a total dose of 60 or 45 Gy is feasible with comparable toxicity and no difference in local control or survival. Distant metastasis is the main cause of death in this disease; the future challenge is thus further improvement of the systemic therapy combined with optimised local TRT.     

Long-term survival in patients with non-small cell lung cancer treated with palliative radiotherapy

The aim of palliative thoracic radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) is to alleviate symptoms. This study was designed to determine whether any patients achieved long-term survival after this treatment. In Edinburgh, between 1974 and 1993, 4531 patients were treated with palliative radiotherapy for NSCLC, receiving ten fractions or fewer. We reviewed the case notes of the long-term survivors. Sixty-one (1.3%; 95% confidence interval (CI) 1.0-1.6) patients survived for more than 5 years; 43 (70%) had histological confirmation of cancer; 28 (46%) had stage Stage I or II, 28 (46%) Stage III and one Stage IV disease; 53 (87%) patients were treated with doses of 30-35 Gy in ten daily fractions, seven (12%) received 20 Gy in five daily fractions and one received a 10 Gy single fraction. Forty-two (69%) patients had a radiological complete response, 16 (26%) a partial response and the remainder stable disease. Clinically significant radiation pneumonitis occurred in one (2%) patient, radiation myelopathy in two (3%) and multiple rib fractures in one (2%). There did not appear to be an association between long-term survival and a radiosensitive phenotype. On univariate analysis, long-term survival was more frequent in patients receiving ten-fraction regimens than in those who underwent a shorter course of radiotherapy (chi 2 = 19.5, P < 0.001). Thirty-four (0.8%; 95% CI 0.6-1.0) patients were disease free at death or at last review (median 10 years; range 5-17). We conclude that palliative thoracic radiotherapy produces long-term survival in 1.3% and personal cure in up to 1% of patients with advanced NSCLC.     

全脑放疗同步或序贯替尼泊甙、顺铂治疗小细胞肺癌脑转移(英文)

Objective: The aim of the study was to compare efficacies and safeties of 2 different treatments of whole brain radiotherapy (WBRT) sequential or concomitant Vm26/DDP for small cell lung cancer (SCLC) patients with brain metastases. Methods: A total of 39 patients were randomly divided into sequential chemoradiotherapy regime (A group, 20 patients) and concomitant chemoradiotherapy regime (B group, 19 patients). The dose of WBRT was 36 Gy in 18–20 fractions, chemotherapy of Vm26/DDP regimen with teniposide ...     

小细胞肺癌脑转移全脑放疗失败后挽救性分次立体定向放疗疗效分析

目的 评价小细胞肺癌(SCLC)全脑放疗(WBRT)后颅内失败分次立体定向放疗(FSRT)挽救的价值。方法 回顾分析WBRT失败后使用FSRT挽救的35例SCLC脑转移患者的生存情况,多因素分析确定和生存相关的预后因素。结果 随访率为100%,中位随访时间11个月。全组总中位生存期为10.3个月,多因素分析显示颅外疾病控制状态和患者的生存相关(χ²=4.02,P=0.045)。自诊断脑转移开始中位生存期为22.0个月,未发现严重晚期不良反应。6、12个月局部控制率分别为91%、76%。6例局部未控患者中3例行二程FSRT挽救,挽救治疗后生存时间分别为3、9、13个月。6例患者FSRT后出现治疗野外新病灶,出现新病灶中位时间为4个月。32例患者死亡,其中14例死于颅内进展,14例死于颅外疾病进展,1例死于脑脊髓膜广泛转移,3例死于其他原因(2例肺部感染,1例死因不明)。结论 FSRT挽救治疗对WBRT后复发SCLC脑转移安全有效。     

探讨NSCLC放射性肺损伤NTCP模型的建立

目的 针对局部晚期NSCLC受累野IMRT后RILI发生情况,分析不同模型建模方法并评价其预测效果。方法 回顾分析2007-2011年间肿瘤医院收治的242例未进行手术治疗的Ⅲ期NSCLC患者临床资料。以放疗结束后6个月内发生2、3级RILI分别作为终点事件。分别采用PCA模型、LKB模型和MLD模型3种计算方法,对剂量学参数建立NTCP预测模型,并评价其预测效果。结果 PCA模型提取4个主成分,2、3级RILI预测结果,AUC分别为0.650、0.606。LKB模型2级RILI参数拟合得到m=0.46,n=1.35,D50=23.59 Gy,3级RILI参数拟合得到m=0.36,n=0.27,D50=72.67 Gy,AUC分别为0.607、0.585。MLD模型2、3级参数预测结果γ50=1.073,D50=24.66 Gy和γ50=0.97,D50=48.45 Gy,AUC分别为0.604和0.569。结论 使用相同治疗模式的单一人群大样本数据进行建模,对提高模型预测准确性和稳定性很重要。LKB模型和PCA模型均能较好地预测RILI的发生概率,MLD模型对3级RILI的预测效果较差。     

肺低剂量区体积与非小细胞肺癌放疗致放射性肺损伤的关系

目的 探讨肺低剂量区体积剂量学参数与非小细胞肺癌（non small cell lung cancer,NSCLC)放疗致放射性肺损伤（radiation induced lung injury,RILI）的关系。方法 收集103例NSCLC放疗患者,通过放疗计划及剂量体积直方图（DVH）获得全肺、患侧肺、健侧肺的剂量体积参数和平均肺受照射剂量（MLD）,采用单因素分析各剂量学参数与≥2级RILI发生的相关性,制作受试者工作特征曲线（ROC）,评价各剂量学参数对RILI的预测价值。结果 发生≥2级RILI 者27例,发生率为26.2%。≥2级RILI患者双肺V₅、双肺MLD、患侧肺V₅、患侧肺V₁₀、健侧肺V₅的相对肺体积均高于＜2级RILI者,差异均有统计学意义（P＜0.05）。ROC曲线分析显示,双肺V₅、双肺MLD、患侧肺V₅、患侧肺V₁₀、健侧肺V₅曲线下面积分别为0.714、0.673、0.690、0.693、0.737,当双肺V₅≥52.22%、双肺MLD≥1 486.75 cGy、患侧肺V5≥62.03%、健侧肺V5≥43.60%、患侧肺V10≥55.67%均可导致肺癌患者≥2级RILI发生率升高（P＜0.001）。 结论 临床制定NSCLC患者根治性放疗计划时,不仅要限定V₂₀、V₃₀、MLD,还应注意低剂量区体积V5对放射性肺损伤的影响。     

Induction and concurrent chemotherapy with concomitant boost radiotherapy in non-small cell lung cancer

This study was designed to evaluate the tolerability and therapeutic activity of paclitaxel and carboplatin combination therapy followed by radical thoracic radiotherapy with a concomitant boost technique with concurrent weekly paclitaxel in good performance status of patients with stage IIIA and IIIB non-small cell lung cancer. Patients with newly diagnosed inoperable non-small cell lung cancer received paclitaxel (100 mg/m²) as a 1-h infusion on d 1,8,15,28,35, and 42. Carboplatin (area under the curve of 6) was given as a 30-min infusion on d 1 and 28. Radiotherapy commenced on d 49 and was delivered with accelerated fractionation with concomitant boost at 1.8 Gy/fraction/d, 5 d/week and 1.5 Gy/fraction/d to a boost field as a second daily treatment for the last 10 treatment days to 60 Gy/35 fractions/5 wk. During radiation treatment, paclitaxel (60 mg/m²) was given as a 1-h infusion once weekly for 5 wk. Twenty-four patients were enrolled in the study. Hematologic toxicities and alopecia were the major acute toxicities during induction chemotherapy; 8.7% of the patients experienced grade 3–4 neutropenia and alopecia. The main acute toxicity of concurrent chemoradiotherapy was esophagitis; grade 3 esophagitis was documented in 23.5% of the patients. No major late toxicity was seen. Overall response rate to the treatment was 65.2%. The median and 1-yr overall-survival rates were 24.9 mo and 63.8%, respectively. The median and 1-yr progression-free survival rates were 9.0 mo and 27.8%, respectively. The main acute toxicities were hematologic toxicity, esophagitis, and alopecia. The response rate and the survival rates achieved with this treatment regimen are particularly noteworthy, especially considering the advanced stage of the patients treated.