细胞因子联合DVH参数预测放射性肺炎的临床研究

目的评价肺癌胸部放疗前及照射40～50 Gy时血浆中TGF-β、IL-6及ACE含量变化、肺受照射剂量体积因素与放射性肺炎发生的关系。方法67例肺癌患者按治疗常规给予放疗或(和)化疗;男60例,女7例,中位年龄58岁(26～81岁)。放疗前、照射40～50 Gy时采血冻存,采用酶联免疫吸附法检测血液中TGF-β、IL-6及ACE含量。放射性肺炎根据CTC AE3.0标准评价,评价终点为≥2级放射性肺炎。结果存活患者中位随访时间22.6个月。2级以上的放射性肺炎发生率25.4%。自放疗开始至发生放射性肺炎的中位时间73天。放疗前、放疗40～50 Gy时血浆中TGF-β、IL-6含量以及其在放疗期间的变化与放射性肺炎无明显相关性。发生放射性肺炎组患者的疗前、疗中血浆ACE含量明显低于未发生肺炎者(P=0.033、0.004)。发生放射性肺炎组的全肺接受10 Gy照射体积(V10)为44%,高于未发生肺炎组的39%(P=0.029)。健肺MLD、V10、V15、V20分别高于未发生肺炎组(1931 cGy:990 cGy、52%:35%、48%:23%、37%:10%,P<0.05)。将生物因素ACE含量和DVH参数联合分析发现疗中血浆ACE含量和全肺V10组合是放射性肺炎最强的预测因素。疗中ACE含量ACE>506 ng/ml且全肺V10≤40%时,放射性肺炎的发生风险最低,13例中无一发生;但如果ACE≤506 ng/ml且全肺V10>40%时,放射性肺炎风险达50%(6/12);其他情况疗中ACE>506 ng/ml且V10>40%或疗中ACE≤506 ng/ml且V10≤40%时,放射性肺炎发生率26.7%(P=0.008)。结论(1)放疗前、放疗中血浆ACE含量低是放射性肺炎发生的高危因素。(2)血浆ACE联合DVH参数V10有望作为预测放射性肺炎发生的指标。     

食管癌三维适形放射治疗剂量学与放射性肺炎发生相互关系的研究

目的:通过食管癌常规放射治疗与三维适形放射治疗的技术对比研究,比较应用不同外照射技术时肿瘤靶区适形指数的差异,以及肺等正常组织受照射容积剂量与放射性肺炎并发症发生概率(NTCP)的关系.方法:应用三维治疗计划系统,对28例胸中段EPC分别设计三种照射技术(A:常规3野;B:适形3野;C:适形5野).比较在同一处方剂量(66 Gy)时肿瘤靶区的适形指数,全肺受照射剂量与肺的NTCP的差异.结果:A、B、C三种照射技术比较:1)靶区的适形指数从0.55±0.09提高至0.76±0.04 和 0.78±0.06.2)肺平均剂量从(16.54±2.35) Gy降低至(13.26±1.93) Gy和(3.38±1.61) Gy;肺的V20从(32.95±6.43)%降低至(23.01±6.25)%和(24.8±4.47)%;肺的V30从(17.25±4.96)% 降低至(12.18±3.66)%和(6.75±2.93)%.3)肺的 NTCP从(6.9±6.86)%降低至(1.14±1.11)%和(1±1.02)%.A、B和C三种照射技术比较差异均有统计学意义,P=0.000.结论:三维适形放射治疗技术的靶区剂量分布较理想,显著降低正常肺的照射体积和剂量,减少放射性肺炎NTCP.     

非小细胞肺癌同期放化疗后重度急性放射性肺炎的预测模型研究北大核心CSCD

目的 利用剂量体积直方图（DVH）参数建立Logistic剂量反应及Lyman-Kutcher-Burman正常组织并发症概率（LKB-NTCP）模型,并评估其对非小细胞肺癌同期放化疗后重度急性放射性肺炎（SARP）的预测价值.方法 搜集2006-2010年间行三维适形放疗同期化疗的147例非小细胞肺癌患者资料.按美国RTOG毒性评价标准定义超过3级的ARP为SARP.根据DVH剂量学信息建立Logistic剂量反应模型和LKB-NTCP模型.结果 SARP发生率为9.5％（14/147）.Logistic剂量反应模型参数：常数b0=-6.66、b1=0.252,TD50=26.43 Gy,γ50=1.67;模型曲线在17 Gy以下相对平坦,17～18 Gy处变为陡峭,SARP风险增大.LKB-NTCP模型参数：体积效应因子n=0.87±0.40,曲线斜率倒数m=0.27 ±0.10,TD50（1）=（29.5±8.0）Gy;Logistic回归及ROC分析均发现此参数下计算出NTCP值对SARP有良好预测价值（P=0.013、0.019）.结论 NTCP值对SARP的预测价值优于简单剂量参数,2个模型曲线均提示最大限制剂量在约17 Gy.     

肺灌注显像联合剂量体积直方图参数预测放射性肺炎的临床研究

 目的　观察接受三维适形或调强放疗的肺癌患者放疗前后肺灌注显像的变化、肺受照射的剂量体积直方图（DVH）参数等,并结合临床因素,探讨其与放射性肺炎发生的相关性。方法　18例接受三维适形或调强放疗的肺癌患者放疗前后行肺灌注显像检查,比较照射前后肺灌注显像的变化。放射性肺炎的评价按美国肿瘤放疗协作组（RTOG）急性放射性肺炎标准评定。获得的CT与单光子发射CT（SPECT）肺灌注图像融合后,将等剂量曲线投影到SPECT图像,将传统的DVH转换成f-DVH。将f-DVH曲线中每例患者的V5、V10和V20所对应的灵敏度与特异度相加,取其最大值,寻找到曲线的界值。分析放疗前后肺灌注显像变化及肺受照射的DVH与放射性肺炎发生的相关性。结果　18例患者中,33.3 %（6／18）发生了2级以上放射性肺炎。放疗前后肺灌注受损加重者2级以上放射性肺炎发生率为62.5 %（5／8）,肺灌注受损改善者发生率为10.0 %（1／10）。f-DVH图曲线中V5、V10和V20的界值分别为53 %、41 %和27 %,以V5对中重度急性放射性肺炎的预测准确度最高。放疗前后肺灌注显像的变化联合全肺DVH参数V5是放射性肺炎最强的预测因素。结论　肺癌患者放疗前后肺灌注显像能反映患侧肺灌注功能的变化。放疗前后肺灌注显像的变化联合DVH参数V5有望作为预测放射性肺炎发生的指标。     

基于EUD鼻咽癌调强放疗中NTCP和TCP的计算程序设计研究

目的 设计一个基于等效均一剂量（EUD）的计算程序来计算鼻咽癌调强放疗（IMRT）计划中正常组织并发症概率（NTCP）和肿瘤控制概率（TCP）。方法 采用具有较强数学特性及友好交互界面等优势的高效编程语言Matlab编写计算NTCP和TCP程序,其中NTCP 数学模型选用基于EUD的Lyman Kutcher Burman模型,而TCP模型则选用Schultheiss逻辑模型 。收集3例接受IMRT治疗的鼻咽癌患者的正常组织和靶区剂量体积直方图（DVH）,计划系统为医科达precise plan。结果编写计算机代码保存为Matlab可执行程序。3例鼻咽癌患者的4种正常组织（脑干、脊髓、左右侧腮腺）和肿瘤的EUD被编写程序算出,进而计算出NTCP和TCP。结论 编写的程序对正常组织耐受量的计算结果与理论值非常吻合,有助于临床选择更安全和高效的治疗方案,将来还可将程序用于其他肿瘤如前列腺癌和肺癌的放疗计划中。     

非小细胞肺癌同期放化疗后重度急性放射性肺炎的预测模型研究

目的 利用剂量体积直方图(DVH)参数建立Logistic剂量反应及Lyman-Kutcher-Burman正常组织并发症概率(LKB-NTCP)模型,并评估其对非小细胞肺癌同期放化疗后重度急性放射性肺炎(SARP)的预测价值。方法 搜集2006—2010年间行三维适形放疗同期化疗的147例非小细胞肺癌患者资料。按美国RTOG毒性评价标准定义超过3级的ARP为SARP。根据DVH剂量学信息建立Logistic剂量反应模型和LKB-NTCP模型。结果 SARP 发生率为9.5%(14/147)。Logistic剂量反应模型参数:常数b₀=－6.66、b₁=0.252,TD₅₀=26.43 Gy,γ₅₀=1.67;模型曲线在17 Gy以下相对平坦,17~18 Gy处变为陡峭,SARP风险增大。LKB-NTCP模型参数:体积效应因子n=0.87±0.40,曲线斜率倒数m=0.27±0.10,TD₅₀₍₁₎=(29.5±8.0) Gy;Logistic回归及ROC分析均发现此参数下计算出NTCP值对SARP有良好预测价值(P=0.013、0.019)。结论 NTCP值对SARP的预测价值优于简单剂量参数,2个模型曲线均提示最大限制剂量在约17 Gy。     

FDG PET-CT标准摄取值在预测放射性肺炎发生中的作用

目的 探讨肺癌患者放射治疗前后FDG PET-CT标准摄取值(SUV)及其变化在预测放射性肺炎发生中的作用.方法 40例未经手术的非小细胞肺癌(NSCLC)患者在放射治疗前后均行PET-CT检查,分别测量出受照≤5 Gy、5.1～15 Gy、15.1～35 Gy、35.1～60 Gy以及>60 Gy肺组织放射治疗前后的平均SUV,比较发生放射性肺炎组与未发生放射性肺炎组SUV的变化情况,以及受照肺组织的SUV与未受照射肺组织SUV值之比(L/B).结果 40例患者中,有8例在治疗后发生放射性肺炎,其中2级6例,3级2例.受照剂量35.1～60 Gy肺组织的SUV与放射性肺炎的发生明显相关,当SUV≥1时,放射性肺炎的发生率为41.7%,明显高于全组放射性肺炎的发生率(20.0%;X2=3.96,P<0.05),SUV预测放射性肺炎的敏感度和特异度分别为62.5%和78.1%.L/B≥2.5时,放射性肺炎的发生率为40.7%,亦明显高于全组放射性肺炎的发生率(20.0%;X2=4.92,P<0.05).以L/B≥2.5为标准预测放射性肺炎的敏感度和特异度分别为72.7%和90.9%.SUV≥1与L/B≥2.5在预测放射性肺炎发生率之间的差异无统计学意义(X2=0.002,P>0.05).结论 SUV和L/B的大小与放射性肺炎的发生呈正相关,临床医生可根据FDG PET-CT提供的SUV和L/B来预测放射性肺炎的发生.     

乳腺癌术后放疗致放射性肺炎的临床分析

目的 探讨乳腺癌术后放疗引起放射性肺炎的相关临床因素.方法 回顾性分析226例术后放疗的乳腺癌,观察放疗的照射野、照射剂量,使用化疗药物的时间、种类,内分泌治疗,患者的年龄和肺部基础病变与放射性肺炎发生率的关系.结果 发生放射性肺炎29例,放射性肺炎的发生率与照射野、照射剂量和使用化疗药物的时间有关(P<0.05),与化疗药物种类和肺部基础病变也有一定关系.结论 照射野和剂量的增加、放疗前化疗及肺部基础病变均会增加放射性肺炎的发生率.     

血液中TGF-β、IL-6及ACE含量在预测放射性肺炎中的价值

目的 评价放疗前血液中TGF-β、IL-6及ACE含量及照射40～50Gy含量变化与放射性肺炎关系.方法 42例入选患者按治疗常规给予放疗或（和）化疗;男38例,女4例,中位年龄57岁（40～81岁）;肺癌39例,食管癌2例,胸腺瘤1例.放疗前、照射40～50Gy时采血冻存,采用酶联免疫吸附法统一检测血液中TGF-β、IL-6及ACE含量.放射性肺炎按RTOG急性放射性肺炎标准评价,评价终点为≥2级放射性肺炎.统计方法采用SPSS 10.0软件.结果 13例发生了放射性肺炎,与未发生放射性肺炎的TGF-β疗前含量分别为7.73、7.48ng/ml（P=0.920）,照射40～50Gy时分别为4.91、3.88 ng/ml（P=0.250）;IL-6疗前含量分别为5.08、7.06pg/ml（P=0.740）,照射40～50Gy时分别为21.75、6.78 pg/ml（P=0.190）;ACE含量疗前分别为394.17、518.22ng/ml（P=0.020）,照射40～50Gy时分别为375.52、497.32 ng/ml（P=0.050）.疗前ACE＜365 ng/ml者6/10发生了放射性肺炎,ACE＞365 ng/ml者6/30发生放射性肺炎（P=0.040）（2例未测）.照射40～50Gy时,TGF-β及IL-6升高者放射性肺炎的发生有所增加,但差异无统计学意义.结论 ACE含量有望作为检测放射性肺炎易感性的指标.     

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.     

Normal tissue complication probabilities: dependence on choice of biological model and dose-volume histogram reduction scheme

PURPOSE: To evaluate the impact of dose-volume histogram (DVH) reduction schemes and models of normal tissue complication probability (NTCP) on ranking of radiation treatment plans. METHODS AND MATERIALS: Data for liver complications in humans and for spinal cord in rats were used to derive input parameters of four different NTCP models. DVH reduction was performed using two schemes: "effective volume" and "preferred Lyman". DVHs for competing treatment plans were derived from a sample DVH by varying dose uniformity in a high dose region so that the obtained cumulative DVHs intersected. Treatment plans were ranked according to the calculated NTCP values. RESULTS: Whenever the preferred Lyman scheme was used to reduce the DVH, competing plans were indistinguishable as long as the mean dose was constant. The effective volume DVH reduction scheme did allow us to distinguish between these competing treatment plans. However, plan ranking depended on the radiobiological model used and its input parameters. CONCLUSIONS: Dose escalation will be a significant part of radiation treatment planning using new technologies, such as 3-D conformal radiotherapy and tomotherapy. Such dose escalation will depend on how the dose distributions in organs at risk are interpreted in terms of expected complication probabilities. The present study indicates considerable variability in predicted NTCP values because of the methods used for DVH reduction and radiobiological models and their input parameters. Animal studies and collection of standardized clinical data are needed to ascertain the effects of non-uniform dose distributions and to test the validity of the models currently in use.     

Early clinical and radiological pulmonary complications following breast cancer radiation therapy: NTCP fit with four different models.

OBJECTIVE: To fit four different NTCP (Normal Tissue Complication Probability) models to prospectively collected data on short-term pulmonary complications following breast cancer radiotherapy (RT). MATERIALS/METHODS: Four hundred and seventy-five breast cancer patients, referred to the Radiotherapy Department at Stockholm S?der Hospital (1994-1998) for adjuvant post-operative RT were prospectively followed for pulmonary complications 1, 4 and 7 months after the completion of RT. Eighty-seven patients with complete dose-volume histogram (DVH) of the ipsilateral lung were selected for the present analysis. Mean dose to the ipsilateral lateral lung ranged from 2.5 to 18Gy (median 12Gy). Three different endpoints were considered: (1) clinical pneumonitis scored according to CTC-NCIC criteria: asymptomatic (grade 0) vs grade 1 and grade 2; (2) radiological changes assessed with diagnostic chest X-ray: no/slight radiological changes vs moderate/severe; (3) radiological changes assessed with CT: no/slight vs moderate/severe. Four NTCP models were used: the Lyman model with DVH reduced to the equivalent uniform dose (LEUD), the Logit model with DVH reduced to EUD, the Mean Lung Dose (MLD) model and the Relative Seriality (RS) model. The data fitting procedure was done using the maximum likelihood analysis. The analysis was done on the entire population (n=87) and on a subgroup of patients treated with loco-regional RT (n=44). RESULTS: 24/87 patients (28%) developed clinical pneumonitis; 28/81 patients (35%) had radiological side effects on chest X-rays and 11/75 patients (15%) showed radiological density changes on Computed Tomography (CT). The analysis showed that the risk of clinical pneumonitis was a smooth function of EUD (calculated from DVH using n=0.86+/-0.10, best fit result). With LEUD, the relationship between EUD and NTCP could be described with a D(50) of 16.4Gy+/-1.1Gy and a steepness parameter m of 0.36+/-0.7. The results found in the overall population were substantially confirmed in the subgroup of patients treated with loco-regional RT. CONCLUSIONS: A large group of prospective patient data (87 pts), including grade 1 pneumonitis, were analysed. The four NTCP models fit quite accurately the considered endpoints. EUD or the mean lung dose are robust and simple parameters correlated with the risk of pneumonitis. For all endpoints the D(50) values ranged in an interval between 10 and 20Gy.     

Dose-volume histograms

A plot of a cumulative dose-volume frequency distribution, commonly known as a dose-volume histogram (DVH), graphically summarizes the simulated radiation distribution within a volume of interest of a patient which would result from a proposed radiation treatment plan. DVHs show promise as tools for comparing rival treatment plans for a specific patient by clearly presenting the uniformity of dose in the target volume and any hot spots in adjacent normal organs or tissues. However, because of the loss of positional information in the volume(s) under consideration, it should not be the sole criterion for plan evaluation. DVHs can also be used as input data to estimate tumor control probability (TCP) and normal tissue complication probability (NTCP). The sensitivity of TCP and NTCP calculations to small changes in the DVH shape points to the need for an accurate method for computing DVHs. We present a discussion of the methodology for generating and plotting the DVHs, some caveats, limitations on their use and the general experience of four hospitals using DVHs.     

乳腺癌根治术后 VMAT技术对心脏受照剂量风险评估

目的：分析乳腺癌根治术后VMAT技术对心脏的物理剂量学和生物学的指标,评估心脏的受照风险。方法随机选取10例左侧乳腺癌根治术后患者,设计4种常用计划：①改良野中野调强计划FIF（8～10个子野）;②四野调强计划4F-IMRT;③五野（增加正对心脏射野）计划5F-IMRT;④包含心脏正对弧双弧VMAT计划。统计每个患者靶区、心脏和冠状动脉左前降支区LAD剂量体积参数,用NTCP-RSM模型计算放射性心脏病死亡率。统计分析VMAT技术的结果与其余技术之间的差异。结果患者心脏Dmean和V25在4种计划下平均值分别是：7．7 Gy,6．9 Gy,9．7 cGy,6．4 Gy;9．1％,7．9％,9．7％,4．9％;LAD的平均剂量分别是29．0 Gy,27．6 Gy,32．8 Gy,26．1 Gy;NTCP的平均值分别为2．7％,1．1％,1．3％,0．86％。靶区CI四套计划平均值为：0．44、0．56、0．61、0．71,HI为0．82、0．78、0．70、0．53,VMAT技术的CI和HI结果与另外3种的结果有统计学差异（ P＜0．05）。结论与常规调强技术相比,包含心脏正对弧的VMAT计划不会显著影响心脏的并发症概率（ NTCP）,同时VMAT计划靶区的CI、HI要优于静态IMRT计划,VMAT技术可以在提高靶区剂量的同时不明显增加心脏的受照风险。     

The role and strategy of IMRT in radiotherapy of pelvic tumors: Dose escalation and critical organ sparing in prostate cancer

PURPOSE: To investigate the intensity-modulated radiotherapy (IMRT) strategy in dose escalation of prostate and pelvic lymph nodes. METHODS AND MATERIALS: Plan dosimetric data of 10 prostate cancer patients were compared with two-dimensional (2D) or IMRT techniques for pelvis (two-dimensional whole pelvic radiation therapy [2D-WPRT] or IM-WPRT) to receive 50 Gy or 54 Gy and additional prostate boost by three-dimensional conformal radiation therapy or IMRT (3D-PBRT or IM-PBRT) techniques up to 72 Gy or 78 Gy. Dose-volume histograms (DVHs), normal tissue complication probabilities (NTCP) of critical organ, and conformity of target volume in various combinations were calculated. RESULTS: In DVH analysis, the plans with IM-WPRT (54 Gy) and additional boost up to 78 Gy had lower rectal and bladder volume percentage at 50 Gy and 60 Gy, compared with those with 2D-WPRT (50 Gy) and additional boost up to 72 Gy or 78 Gy. Those with IM-WPRT (54 Gy) also had better small bowel sparing at 30 Gy and 50 Gy, compared with those with 2D-WPRT (50 Gy). In NTCP, those with IM-WPRT and total dose of 78 Gy achieved lower complication rates in rectum and small bowel, compared with those of 2D-WPRT with total dose of 72 Gy. In conformity, those with IM-WPRT had better conformity compared with those with 2D-WPRT with significance (p < 0.005). No significant difference in DVHs, NTCP, or conformity was found between IM-PBRT and 3D-PBRT after IM-WPRT. CONCLUSIONS: Initial pelvic IMRT is the most important strategy in dose escalation and critical organ sparing. IM-WPRT is recommended for patients requiring WPRT. There is not much benefit for critical organ sparing by IMRT after 2D-WPRT.     

Comparative analysis of dose volume histogram reduction algorithms for normal tissue complication probability calculations

A model for estimating radiotherapy treatment outcome through the probability of damage to normal tissue and the probability of tumour control is a useful tool for treatment plan optimization, dose escalation strategies and other currently used procedures in radiation oncology. Normal tissue complication estimation (NTCP) is here analysed from the point of view of the reliability and internal consistency of the most popular model. Five different dose volume histogram (DVH) reduction algorithms, applied to the Lyman model for NTCP calculation, were analysed and compared. The study was carried out for sets of parameters corresponding to quite different expected dose-response relationships. In particular, we discussed the dependence of the models on the parameters and on the dose bin size in the DVH. The sensitivity of the different reduction schemes to dose inhomogeneities was analysed, using a set of simple DVHs representing typical situations of radiation therapy routine. Significant differences were substantiated between the various reduction methods regarding the sensitivity to the degree of irradiation homogeneity, to the model parameters and to the dose bin size. Structural aspects of the reduction formalism allowed an explanation for these differences. This work shows that DVH reduction for NTCP calculation has still to be considered as a very delicate field and used with extreme care, especially for clinical applications, at least until the actual formulations are tuned against strong clinical data.     

Comparison of three accelerated partial breast irradiation techniques: treatment effectiveness based upon biological models.

BACKGROUND AND PURPOSE: Accelerated partial breast irradiation (APBI) is being studied in a phase III randomized trial as an alternative to whole breast irradiation (WBI) for early stage breast cancer patients. There are three methods for APBI: multi-catheter brachytherapy (MCT), MammoSite brachytherapy (MST), or 3D conformal (3DCRT). There is a paucity of data comparing among methods. Using a linear-quadratic (LQ) model, we evaluated the anticipated efficacy among the APBI methods for equivalent uniform dose (EUD), Tumor Control Probability (TCP), and Normal Tissue Complication Probability (NTCP). MATERIALS AND METHODS: Treatment plans from five patients treated by each APBI modality were retrospectively selected. Dose-volume-histograms (DVH) for planning target volume (PTV), breast, and lung were generated. The LQ parameters alpha=0.3Gy(-1) and alpha/beta=10Gy were used for calculations. The values of EUD, TCP, and NTCP were calculated based on DVHs. RESULTS: The average EUD (normalized to 3.4Gy BID) for the MCT, MST, and 3DCRT APBI was 35, 37.2, and 37.6Gy. When normalized to 2Gy fractionation these become, 42.2, 46.4, and 46.9Gy. Average TCP for MCT, MST, and 3DCRT PBI was 94.8%, 99.1%, and 99.2%. The NTCP values for breast and lung were low for all three methods. CONCLUSIONS: The EUD for PTV and TCP were most similar in MST and 3DCRT APBI and were lower in MCT APBI. This questions the equivalence of the three APBI modalities that are currently being evaluated in the NSABP-B39/RTOG 0413 protocol.     

Reduction of cardiac and lung complication probabilities after breast irradiation using conformal radiotherapy with or without intensity modulation.

PURPOSE: The main purpose of this work is to reduce the cardiac and lung dose by applying conformal tangential beam irradiation of the intact left breast with and without intensity modulation, instead of rectangular tangential treatment fields. The extension of the applicability of the maximum heart distance (MHD) to conformal tangential fields as a simple patient selection criterion, identifying patients for which rectangular and conformal tangential fields without intensity modulation will result in unacceptable normal tissue complication probability (NTCP) values for late cardiac mortality (e.g. >2%), was also investigated. MATERIALS AND METHODS: Three-dimensional treatment planning was performed for 17 left-sided breast cancer patients. Three different tangential beam techniques were compared: (1) optimized wedges without blocks, (2) optimized wedges with conformal blocks and (3) intensity modulation. Plans were evaluated using dose-volume histograms (DVHs) for the planning target volume (PTV), the heart and the lungs. NTCPs for radiation pneumonitis and late cardiac mortality were calculated using the DVH data. The MHD was measured for all rectangular (MHD(rectangular)) and conformal (MHD(conformal)) treatment plans. RESULTS: For all patients, on average, part of the PTV receiving a dose between 95 and 107% of the prescribed dose of 50Gy in 25 fractions of 2Gy was 90.8% (standard deviation (SD): 5.0%), 92.8% (SD: 3.5%) and 92.8% (SD: 3.6%) for the intensity modulation radiation therapy (IMRT), conformal and rectangular field treatment techniques, respectively. The NTCP for radiation pneumonitis was 0.3% (SD: 0.1%), 0.4% (SD: 0.4%) and 0.5% (SD: 0.6%) for the IMRT, conformal and rectangular field techniques, respectively. The NTCP for late cardiac mortality was 5.9% (SD: 2.2%) for the rectangular field technique. This value was reduced to 4.0% (SD: 2.3%) with the conformal technique. A further reduction to 2.0% (SD: 1.1%) could be accomplished with the IMRT technique. The NTCP for late cardiac mortality could be described as a second order polynomial function of the MHD. This function could be described with a high accuracy and was independent of the technique for which the MHD was determined (r(2)=0.88). In order to achieve a NTCP value for late cardiac mortality below 1, 2 or 3%, the MHD should be equal to or smaller than 11, 17 or 23 mm, respectively. If such a maximum complication probability cannot be accomplished, a treatment using the IMRT technique should be considered. CONCLUSIONS: The use of conformal tangential fields decreases the NTCP for late cardiac toxicity on average by 30% compared to using rectangular fields, while the tangential IMRT technique can further reduce this value by an additional 50%. The MHD can be used to estimate the NTCP for late cardiac mortality if rectangular or conformal tangential treatment fields are used.     

Node-positive left-sided breast cancer patients after breast-conserving surgery: potential outcomes of radiotherapy modalities and techniques.

PURPOSE: To determine how much proton and intensity modulated photon radiotherapy (IMRT) can improve treatment results of node-positive left-sided breast cancer compared to conventional radiation qualities (X-rays and electrons) after breast-conserving surgery in terms of lower complication risks for cardiac mortality and radiation pneumonitis. METHODS AND MATERIAL: For each of 11 patient studies, one proton plan, one IMRT, and two conventional (tangential and patched) plans were calculated using a three-dimensional treatment-planning system, Helax-TMS(). The evaluation of the different treatment plans was made by applying the normal tissue complication probability model (NTCP) proposed by K?llman (also denoted the relative seriality model) on the dose distributions in terms of dose-volume histograms. The organs at risk are the spinal cord, the left lung, the heart, and the non-critical normal tissues (including the right breast). RESULTS: The comparison demonstrated that the proton treatment plans provide significantly lower NTCP values for the heart and lung when compared to conventional radiation qualities including IMRT for all 11 patients. At a prescribed dose of 50 Gy in the PTV, the calculated mean NTCP value for the patients decreased, on the average, from 14.7 to 0.6% for the lung (radiation pneumonitis) for the proton plans compared with the best plan using conventional radiation qualities. The corresponding figures for the heart (cardiac mortality) were from 2.1 to 0.5%. The figures for cardiac mortality for IMRT, tangential technique and the patched technique were 2.2, 6.7, and 2.1%, respectively. CONCLUSIONS: Protons appear to have major advantages in terms of lower complication risks when compared with treatments using conventional radiation qualities for treating node-positive left-sided breast cancer after breast-conserving surgery.