心脏正对射野(弧)对乳腺癌根治术后放疗剂量学风险和收益分析

目的 研究乳腺癌根治术后不同放疗技术靶区、正常组织剂量学差异。方法 对2012—2013年间31例乳腺癌(左侧9例、右侧22例)根治术后患者采用改良野中野IMRT计划(P₁)、4个野IMRT计划(P₂)、含心脏正对野5个野IMRT计划(P₃)、含心脏正对弧VMAT计划(P₄)分别计算靶区CI、HI,心脏、冠状动脉左前降支、右冠状动脉、患侧肺剂量学参数,分别用NTCP_RSM、NTCP_Lyman、LQ-TCP-Poisson模型计算左右侧乳腺癌患者放射性心脏病概率、RP概率、TCP,结果用方差分析或χ²检验。结果 P₁—P₄间左侧和右侧乳腺癌患者靶区CI、HI值均不同(P=0.009、P=0.000和P=0.000、0.000),放射性心脏病概率平均值相近[左侧2.7%、1.1%、1.3%、0.86%(P=0.397);右侧0.19%、4.76×10^－3%、0、0(P=0.568)],RP概率平均值也相近[左侧9.73%、7.52%、8.86%、10.73%(P=0.953),右侧11.73%、8.65%、7.02%、11.25%(P=0.437)],但TCP均不同(左侧P=0.000,右侧P=0.000)。结论 乳腺癌根治术后增加心脏正对射野(弧)不同放疗计划对放射性心、肺并发症概率均无显著影响,但可显著改善计划靶区的CI、HI,增加TCP;5个野IMRT和VMAT技术可选为乳癌根治术后放疗手段。     

早期左侧乳腺癌保乳术后大分割放疗同期瘤床加量的安全性及心脏亚结构剂量评估的重要性研究

背景与目的：早期乳腺癌保乳术后辅助大分割放疗已被指南推荐,但大分割放疗同期瘤床加量是否可行目前尚无定论。本随机对照研究对大分割同期瘤床加量和常规分割同期瘤床加量两种放疗计划的心脏剂量学参数和心超指标等进行比较,以评估前者在心脏毒性方面的安全性。方法：纳入复旦大学附属中山医院2017年3月—2018年3月收治的符合入组标准的早期乳腺癌保乳术后左侧乳腺癌患者40例,随机分为两组,20例制定大分割同期瘤床加量放疗计划(全乳放疗剂量4 005 cGy/15次,同期瘤床加量至4 500 cGy/15次),20例制定常规分割同期瘤床加量放疗计划(全乳放疗剂量5 000 cGy/25次,同期瘤床加量至6 000 cGy/25次),比较两组患者的心脏剂量学参数和心脏超声检查指标,剂量学参数包括全心脏、左心室、右心室、右室游离壁、室间隔和冠状动脉左前降支(left anterior descending,LAD)的平均剂量(D_mean)以及各结构受到5～35 Gy照射的相对体积分数(V_{5 Gy}～V_{35 Gy})。心超随访指标包括主动脉根部直...     

晚期肺癌非共面和共面IMRT剂量学比较研究

目的 比较研究晚期肺癌非共面IMRT计划剂量学分布特点,并观察计划执行安全性。方法 对14例晚期肺癌患者优化设计共面和非共面5、7个野IMRT计划,对比共面、非共面各组内及组间计划优化结果。观察4例患者非共面7个野计划的执行过程。结果 随射野数目增加共面及非共面靶区CI均改善(P值均为0.000),非共面野靶区D_mean、D_max、V_95%、HI亦有改善(P=0.001、0.001、0.009、0.000);共面野全肺、患、健肺V₅增加(P=0.000、0.002、0.000)及全肺D_mean增加(P=0.000),相反非共面野全肺、健肺V₅降低(P=0.001、0.005)。组间非共面7个野较共面5个野计划靶区各指标均改善(P值均为0.000);各肺V₂₀均降低(P值均为0.000)且全肺D_mean、V₃₀及健肺V₅降低(P=0.000、0.001、0.000),脊髓D_max亦有减少(P=0.033);但患肺V₅及心脏D_mean增加(P=0.000、0.003)。较共面7个野计划患肺V₅及心脏D_mean亦增加(P=0.000、0.048),但全肺及健肺V₅均降低(所有P=0.000)。4例患者均顺利完成非共面IMRT,全程未发生碰撞风险。结论 非共面7个野IMRT计划改善了靶区剂量分布,降低肺V₂₀、D_mean也控制了低剂量肺体积增加趋势且临床实施安全有效,值得推荐。     

左乳腺癌保乳术后CRT和FIF-IMRT及逆向IMRT剂量学比较

目的 比较左乳腺癌保乳术后CRT、FIF-IMRT和IMRT剂量学差异。方法 随机选取31例左乳腺癌保乳术后患者,分别制定CRT、FIF-IMRT、IMRT计划。通过DVH图进行自身对照研究,采用非参数检验法比较靶体积及OAR受量分布差异。结果 3种方法均能达到处方剂量要求。CRT组靶区V₁₀₅高、心脏V₃₀、D_max较高(P=0.000、0.000、0.000);IMRT组V₅、D_mean较高(P=0.000、0.000),左肺V₅较高(P=0.000)、V₄₀较低(P=0.000);FIF-IMRT组D_mean最低(P=0.000),IMRT组右肺及脊髓D_mean、D_max均高于其他两组(P=0.000、0.000、0.000、0.000)。单次跳数FIF-IMRT组明显低于其他两组(P=0.000)。结论 CRT在靶区有较好的剂量分布但对周围组织损伤较大,相比而言FIF-IMRT对OAR保护更好且对机器损耗小。     

乳腺癌保乳术后患者因素对调强放疗计划设计的影响分析 (此文经查为一稿多投，本刊作撤稿处理。《肿瘤学杂志》编辑部2018-6-26）

摘 要：［目的］ 探讨患者的心胸比（cardiothoracic ratio,CTR）,肺脏最大距离（central lung distance,CLD）,心脏最大距离（maximum heart distance,MHD）,计划靶区体积(VPTV)对乳腺癌保乳术后两种调强放疗计划结果的各个目标参数值的预测。［方法］ 2016年6月至2017年3月在我院接受全乳调强放疗的48例女性乳腺癌保乳术后患者（31例左侧,17例右侧）,患者PTV处方剂量为 50Gy,分割剂量2Gy/次。PTV达到95%的处方剂量为满足临床要求。每个患者设计两个治疗计划,P1为三维适形+逆向调强的混合计划（3DCRT+IMRT）,三维适形计划为两野切线野,剂量为80%处方剂量;IMRT为四野的逆向静态调强计划,剂量为20%处方剂量,P2为6野全切线野的逆向静态调强计划,P1和P2计划子野都是24个。调强计划同时使用物理参数和等效生物剂量（EUD）对目标函数进行优化。预测影响因子与适形度指数（CI）、均匀性指数（HI）、危及器官（OAR）的剂量体积关系采用单因素和多元线性回归进行分析。［结果］ （1）MHD是左侧乳腺癌P１计划VHeart30、VHeart10、DmeanHeart的独立预测影响因子。P１计划的预测公式：VHeart30-P1=-1.3+4.5MHD,MHD、CTR是左侧乳腺癌P２计划VHeart30的独立预测影响因子,P2计划的预测公式：VHeart30-P2=-13.7+1.89 MHD+30.53CTR。（2）CLD是左侧乳腺癌P１、P２计划Vlung20、Vlung10、Dmeanlung的预测影响因子和独立预测影响因子,预测公式：Vlung20-P1=10.6+3.9CLD,Vlung20-P2=12.7+3.2CLD。（3）VPTV是左侧乳腺癌P1计划CI的独立预测因子,VPTV、CTR是左侧乳腺癌P２计划CI的独立预测因子,VPTV的B值系数均为0,预测公式：左侧CIP1-左=0.54,CIP2-左＝0.38+0.32CTR;MHD是左侧乳腺癌P1计划HI的独立预测因子,CLD左侧乳腺癌P２计划HI的独立预测因子,预测公式：左侧乳腺癌HIP1-左=1.08+0.006MHD,HIP2-左=1.06+0.015CLD;CTR是右侧乳腺癌P１计划CI的独立预测影响因子,VPTV是右侧乳腺癌P2计划CI的独立预测影响因子,预测公式：右侧CIP1-右=0.23+0.85CTR,CIP2-右＝0.48。［结论］ 预测因子CTR、CLD、MHD更适用于左侧乳腺保乳术后的全切线野的逆向静态调强计划结果的初步预测。预测公式可以快速计算计划的CI值、HI值、肺V20和心脏V30的预测值,有助于物理师或剂量师快速选择治疗计划的设计方案,提高临床治疗计划设计的有效性。     

保乳术后腋窝淋巴结标准切线野与多野放疗的剂量学比较

目的 评价标准切线野对腋窝Ⅰ、Ⅱ站淋巴结覆盖情况,分析调强计划处方剂量给予腋窝淋巴结时正常组织剂量。方法 回顾分析15例左侧乳腺癌接受保乳手术、前哨淋巴结活检和全乳放疗。放疗计划以标准切线野为基础采用逆向调强方法优化。按照RTOG标准勾画Ⅰ、Ⅱ站腋窝淋巴结,以原始计划计算1组和2组腋窝淋巴结靶区覆盖程度。每个患者设计全乳腋窝IMRT计划,CTV包括全乳和Ⅰ、Ⅱ站腋窝淋巴结。处方剂量均为50 Gy分25次。计算靶区HI和CI及OAR的参数。结果 标准切线野计划中Ⅰ、Ⅱ站腋窝淋巴结D_mean分别为34.4、21.9 Gy。腋窝Ⅰ站V₅₀、V₄₀分别为22.6%、49.9%,Ⅱ站分别为6.0%、22.0%。全乳腋窝调强计划降低了全乳照射剂量均匀性,PTV适形性也较差,并明显增加了同侧肺和心脏剂量,同侧肺V₂₀由17.1%增至34.2%,D_mean由999 cGy增至1732 cGy。结论 标准切线野不能很好覆盖Ⅰ、Ⅱ站腋窝淋巴结。需要腋窝放疗者应行IMRT计划以保证腋窝接受足够剂量,但正常组织剂量明显增加。     

乳腺癌保乳术后螺旋断层治疗技术的剂量学研究

目的 研究乳腺癌保乳术后患者应用固定野调强放疗(FF-IMRT)和螺旋断层治疗(HT)计划的剂量学差异。方法 选择10例左侧乳腺癌保乳术后IMRT患者,CT模拟定位、勾画靶区及危及器官,对同一CT图像设计FF-IMRT计划和HT计划。配对t检验两种计划靶区及危及器官剂量分布及照射时间差异。结果 与FF-IMRT计划相比,HT计划的100%PTV覆盖度增加(P=0.000),105%PTV覆盖度降低(P=0.000),平均剂量(D_mean)降低(P=0.002),均匀指数(HI)、适形指数(CI)增加(P=0.001、0.023)。HT计划的患侧肺剂量体积V₅、V₁₀、V₂₀、V₃₀、V₄₀、D_mean分别降低28%、30%、35%、46%、61%、32%(P=0.000),双肺的分别降低30%、28%、34%、46%、62%、26%(P=0.000),心脏的和最大剂量(D_max)分别降低57%、59%、71%、82%、91%、45%和12%(P=0.000~0.002),健侧乳腺D_mean、D_max分别增加0.9、3.0 Gy (P=0.000、0.000),健侧肺的分别增加0.42、2.70 Gy (P=0.000、0.000)。HT计划照射时间明显高于FF-IMRT计划(11.98 min:5.96 min,P=0.000)。结论 左侧如乳腺癌HT计划的靶区均匀性和适形度均优于FF-IMRT计划,危及器官可获得等同于或优于FF-IMRT计划的剂量分布,可作为新照射方式用于乳腺癌保乳术后患者。     

左侧乳腺癌保乳术后采用深吸气屏气放疗的心脏剂量学分析

目的 探究左侧乳腺癌保乳术后放疗患者采用深吸气屏气(DIBH)技术对心脏剂量的改善情况,分析可能影响心脏剂量的解剖因素。方法 前瞻性入组 15例左侧乳腺癌保乳术后行全乳放疗患者,符合呼吸控制要求。分别在自由呼吸(FB)和DIBH状态下进行2次模拟CT扫描,在DIBH图像上制定全乳放疗计划。比较FB和DIBH状态下心肺位置和体积变化以及心肺剂量差异,探究FB状态下各解剖因素与心脏剂量的相关性。对计数资料组间行非参数Wilcoxon秩和检验,双变量相关分析采用Pearson法。结果 DIBH与FB状态下心脏体积相似(P=0.773),而双肺体积明显增加(P=0.001)。心脏、冠脉左前降支、左心室、右心室和左肺 Dmean、Dmax和V5—V40均明显降低(P<0.05)。DIBH使肺体积增加越显著,心脏平均剂量下降幅度越大。FB状态下乳腺体积、心肺体积比、乳腺下界与心脏下界距离、最大心脏切缘距离分别与心脏剂量呈线性相关,其中心肺体积比、最大心脏切缘距离与心脏剂量具有独立相关性。结论 左侧乳腺癌保乳术后采用DIBH技术行全乳放疗较FB状态明显降低心肺剂量。肺体积的变化是改善心脏相对解剖位置的基础。心肺体积比、最大心脏切缘距离或许可以作为进行DIBH技术治疗的参考标准。     

左乳腺癌保乳术后全乳和锁骨上下及内乳淋巴结区三种放疗方式的剂量学研究

  目的  对左乳腺癌保乳术后全乳及锁骨上下、内乳淋巴结引流区三种放疗方式在靶区及危及器官（organs at risk，OARs）的剂量学进行研究。  方法  选取2018年1月至2019年10月20例于昆明医科大学第一附属医院行左乳腺癌保乳术后放疗患者的定位CT资料，设计固定野滑窗调强放疗（dynamic multi-leaf collimator，dMLC）、容积弧形调强放疗（volumetric intensity modulated arctherapy，VMAT）和螺旋断层放疗（tomotherapy，HT）三种计划，并对剂量指标进行统计学分析。  结果  HT在术后瘤床（plan targetvolume of tumor bed，PTV_tb）的平均剂量（mean dose，D_mean）、D₁、适形度（homogeneity index，HI）和全乳及淋巴引流区的计划靶区（plan target volume，PTV）的D_mean、均匀性（conformity index，CI）均优于dMLC和VMAT，并且降低心脏和患侧肺的D_mean、V₅、V₁₀、V₃₀。HT在冠状动脉左前降支和右冠状动脉的D_mean以及D₁比较中剂量最低，但相比VMAT及dMLC，HT增加健侧乳腺的D₁和D_mean。  结论  对左乳腺癌保乳术后患者，HT对降低心脏毒性和保护患侧肺最有优势，但对健侧肺低剂量控制不如VMAT和dMLC，dMLC对健侧肺及健侧乳腺低剂量控制最佳，但对心脏及患侧肺的高剂量控制最差。在临床中需根据实际情况选择合适的计划方式。      

宫颈癌九野均分与角度优化IMRT计划剂量学比较

目的 比较宫颈癌术后患者9个野均分和角度优化的IMRT计划靶区和OAR剂量学参数差异。方法 对 12例宫颈癌术后患者CT图像分别设计9个野均分IMRT计划和利用角度优化产生9个野IMRT计划。评估靶区及OAR剂量分布并配对t检验差异。结果 射野角度优化与均分IMRT计划相比,PTV的 V_95%、V_105%、V_110%分别为99.31%∶99.42%(P=0.020)、60.54%∶47.92%(P=0.013)、7.14%∶0.37%(P=0.000);D_max、D_mean分别为56.62 Gy∶55.47 Gy (P=0.000)、53.29 Gy∶52.72 Gy (P=0.000);CI、HI分别为0.85∶0.89(P=0.000)、0.10∶0.13(P=0.000);膀胱 V₄₀增加约4.7%(P=0.013),直肠 D₄₀增加约0.5 Gy (P=0.004),小肠 V₄₀升高约0.6%(P=0.015)、D_max增加1.4 Gy (P=0.000),骨髓 D_mean均升高约1.3 Gy (P=0.000),马尾神经 D_{0.1 cm³}增加2.0 Gy (P=0.000)。结论 9个野均分IMRT计划质量明显优于通过射野角度优化的IMRT计划。     

Multileaf Collimation Cardiac Shielding in Breast Radiotherapy: Cardiac Doses are Reduced,But at What Cost?

AimsTo measure cardiac tissue doses in left-sided breast cancer patients receiving supine tangential field radiotherapy with multileaf collimation (MLC) cardiac shielding of the heart and to assess the effect on target volume coverage.Materials and methodsSixty-seven consecutive patients who underwent adjuvant radiotherapy to the left breast (n = 48) or chest wall (n = 19) in 2009/2010 were analysed. The heart, left anterior descending coronary artery (LAD), whole breast and partial breast clinical target volumes (WBCTV and PBCTV) were outlined retrospectively (the latter only in patients who had undergone breast-conserving surgery [BCS]). The mean heart and LAD NTD_mean and maximum LAD doses (LAD_max) were calculated for all patients (NTD_mean is a biologically weighted mean dose normalised to 2 Gy fractions using a standard linear quadratic model). Coverage of WBCTV and PBCTV by the 95% isodose was assessed (BCS patients only).ResultsThe mean heart NTD_mean (standard deviation) was 0.8 (0.3) Gy, the mean LAD NTD_mean 6.7 (4.3) Gy and the mean LAD_max 40.3 (10.1) Gy. Coverage of the WBCTV by 95% isodose was <90% in one in three patients and PBCTV coverage <95% (range 78–94%) in one in 10 BCS patients.ConclusionThe use of MLC cardiac shielding reduces doses to cardiac tissues at the expense of target tissue coverage. Formal target volume delineation in combination with an assessment of the likelihood of local relapse is recommended in order to aid decisions regarding field and MLC placement.     

Analysis of coronary artery dosimetry in the 3-dimensional era: Implications for organ-at-risk segmentation and dose tolerances in left-sided tangential breast radiation

PurposeTo evaluate the dose to the left anterior descending artery in patients receiving left-sided tangential breast radiation.Methods and MaterialsThe study cohort consisted of 50 left-sided breast cancer patients who were sequentially simulated at our institution. The heart and left anterior descending (LAD) artery were contoured from its origin on the left main coronary artery down to the last visible segment of the vessel. Detailed dosimetry of the heart and LAD artery were obtained and analyzed.ResultsExcellent correlation between the dose to the heart and LAD artery was discovered. The mean LAD dose was 17.98 Gy. The mean dose to the proximal LAD was 2.46 Gy. The median V25 was 2.91% and the mean heart dose 3.10 Gy. For every 100 cGy increase in mean heart dose, mean LAD dose increased by 4.82 Gy. For every percent increase in the heart V10 and V25, there was a 2.23 Gy and 2.77 Gy increase in mean LAD dose, respectively. For every percent increase of heart V25, a 5.6% increase in the LAD V20 was demonstrated.ConclusionsThe LAD artery dose correlates very closely with all of the commonly measured heart dose constraints, and does not need to be contoured separately when standard tangential borders are used. Incidental LAD artery doses remain with supine breast tangential radiation therapy.     

Non-coplanar Volumetric Modulated Arc Therapy for Locoregional Radiotherapy of Left-sided Breast Cancer Including Internal Mammary Nodes

BackgroundNon-coplanar volumetric modulated arc therapy (ncVMAT) is proposed to reduce toxicity in heart and lungs for locoregional radiotherapy of left-sided breast cancer, including internal mammary nodes (IMN).Patients and methodsThis retrospective study included 10 patients with left-sided breast cancer who underwent locoregional radiotherapy after breast-conserving surgery. For each patient, the ncVMAT plan was designed with four partial arcs comprising two coplanar arcs and two non-coplanar arcs, with a couch rotating to 90°. The prescribed dose was normalized to cover 95% of planning target volume (PTV), with 50 Gy delivered in 25 fractions. For each ncVMAT plan, dosimetric parameters were compared with the coplanar volumetric modulated arc therapy (coV-MAT) plan.ResultsT here were improvements in conformity index, homogeneity index and V₅₅ of total target volume (PTVall) comparing ncVMAT to coVMAT (p < 0.001). Among the organs at risk, the average V₃₀, V₂₀, V₁₀, V₅, and mean dose (D_mean) of the heart decreased significantly (p < 0.001). Furthermore, ncVMAT significantly reduced the mean V₂₀, V₁₀, V₅, and D_mean of left lung and the mean V₁₀ and V₅ and D_mean of contralateral lung (p < 0.001). An improved sparing of the left anterior descending coronary artery and right breast were also observed with ncVMAT (p < 0.001).ConclusionsCompared to coVMAT, ncVMAT provides improved conformity and homogeneity of whole P TV, better dose sparing of the heart, bilateral lungs, left anterior descending coronary artery (LAD), and right breast for locoregional radiotherapy of left-sided breast cancer with IMN, potentially reducing the risk of normal tissue damage.Key words: non-coplanar, volumetric, modulated arc therapy, left-sided breast cancer, internal mammary nodes     

VMAT techniques for lymph node-positive left sided breast cancer

PurposeTo investigate the plan quality of two different volumetric modulated arc therapy (VMAT) techniques for lymph node-positive left-sided breast cancer.MethodsTwo VMAT plans were generated for 10 lymph node-positive left-sided breast cancer patients: one plan using one single segment of a full rotation, typically an arc segment of 230° (1s-VMAT); and a second plan consisting of 2 small tangential arc segments of about 50° (2s-VMAT).For plan comparison, various dose and dose volume metrics (D_mean, D_98%, D_2% for target volumes, D_2%, D_mean and V_x% for organs at risk (OAR)) were evaluated.ResultsBoth techniques fulfilled both clinical target dose and OAR goals. 1s-VMAT achieved a slightly better homogeneity and better target coverage (D_2%= 54.2 ± 0.7 Gy, D_98%= 30.3 ± 1.8 Gy) compared to 2s-VMAT (D_2%= 55.0 ± 1.1 Gy, D_98%= 29.9 ± 1.7 Gy). For geometrical reasons, OAR sparing was noticeable but not significant better using 2s-VMAT, particularly heart and contralateral breast. The heart received a mean dose of 4.4 ± 0.8 Gy using 1s-VMAT and 3.3 ± 1.0 Gy using 2s-VMAT; the contralateral breast received 1.5 ± 0.3 Gy and 0.9 ± 0.3 Gy, respectively.ConclusionsA VMAT technique based on two small tangential arc segments enables improved OAR sparing; the differences between the two techniques in target coverage and homogeneity are minor. Patient age and –anatomy must be considered for each individual case when deciding which technique to be used.     

宫颈癌术后盆腔容积调强弧形治疗与固定野调强放疗计划的剂量学研究

目的 研究宫颈癌术后患者应用固定野调强放疗(FF-IMRT)和容积调强弧形治疗(VIMAT)计划剂量学差异。方法 选择 13例宫颈癌术后调强放疗患者CT模拟定位并勾画靶区及危及器官,对同一CT图像设计FF-IMRT计划和VIMAT计划,评估计划靶体积(PTV)及危及器官的剂量学参数。两种计划参数比较用配对t检验。结果 与FF-IMRT计划相比,VIMAT计划PTV的95%覆盖度增加(t=9.84,P=0.000)、110%覆盖度降低(t=－3.72,P=0.003)、最大剂量(D_max)降低(t=－3.51,P=0.005)、适形指数变差(t=5.93,P=0.000),但PTV105%覆盖度、平均剂量(D_mean)、不均匀指数均相似(t=－0.02、－0.60、1.13,P=0.842、0.560、0.283);膀胱 V₃₀降低约10%(t=－4.99,P=0.000)、D_mean降低1.4 Gy (t=－3.65,P=0.004)、D_max降低1.5 Gy (t=－18.03,P=0.000),直肠 V₄₀降低约10%(t=－2.99,P=0.012),D_mean降低0.6 Gy (t=－2.98,P=0.013)、D_max降低0.8 Gy (t=－4.05,P=0.002),小肠 V₄₀降低最多(10%)(t=－4.74,P=0.001)、D_max降低0.8 Gy (t=－9.45,P=0.000),骨髓 V₅₀降低最多(16%)(t=－4.04,P=0.002)、D_mean降低1.9 Gy (t=－16.21,P=0.000),左、右股骨头 D₅和马尾神经 D_max分别降低1.6、2.7 Gy和1.5 Gy (t=－2.89、－6.22、－4.80,P=0.015、0.000、0.001);机器跳数减少57%(t=－40.54,P=0.000)。结论 宫颈癌患者采用VIMAT技术可获得等同于或优FF-IMRT计划的剂量分布,机器数量明显降低,但其疗效还需进一步临床评估。     

Diastolic Dysfunction Occurs Early in HER2‐Positive Breast Cancer Patients Treated Concurrently With Radiation Therapy and Trastuzumab

Background.

Left ventricular ejection fraction (LVEF) is used routinely to monitor cardiac dysfunction associated with breast cancer treatment. In this study the prevalence of early left ventricular diastolic dysfunction (LVDD) and its relationship to the dose-volume of the heart irradiated were evaluated in HER2-positive breast cancer patients undergoing concurrent trastuzumab and adjuvant radiotherapy (RT).

Materials and Methods.

Data from 40 breast cancer patients treated with concurrent trastuzumab and left-sided adjuvant RT between September 2011 and October 2012 were collected prospectively. For comparison, 32 patients treated with concurrent trastuzumab and right-sided adjuvant RT and 71 patients treated with left-sided RT alone were collected retrospectively. Echocardiography was obtained before RT, immediately following RT, and 3 and 6 months after RT. Doses to the heart and left ventricle (LV) were quantified.

Results.

Prior to RT with concurrent trastuzumab, 11 of 29 (left) and 8 of 25 (right) patients with normal baseline left ventricular diastolic function (LVDF) developed LVDD. In patients receiving left-sided RT alone, 12 of 61 patients with normal baseline LVDF developed LVDD. D_mean, D₁₅–D₄₀, D₆₀–D₇₀, and V₃–V₁₀ of the LV were significantly higher in patients who developed LVDD after concurrent trastuzumab and left-sided RT. In contrast, only two patients developed grade 1 LVEF decrease after both concurrent treatment and left-sided RT alone.

Conclusion.

Changes in LVDF compared with LVEF are more sensitive for early detection of cardiotoxicity. The dose-volume of the heart contributes significantly to the risk of LVDD in patients with left-sided breast cancer treated concurrently with trastuzumab.

Implications for Practice:

Abnormalities in diastolic function are more sensitive than changes in the left ventricular ejection fraction for detecting acute cardiotoxicity and are related to the dose-volume of the heart irradiated in patients with left-sided breast cancer receiving radiotherapy concurrently with trastuzumab. This result highlights the importance of decreasing the dose-volume of heart irradiated as a protective strategy in the treatment setting of concurrent trastuzumab and radiotherapy. Diastolic dysfunction may serve as a more sensitive tool for the early detection of cardiac damage and should be incorporated as a routine parameter in the functional monitoring of cardiotoxicity.     

Cardiotoxic effects of tangential breast irradiation in early breast cancer patients: the role of irradiated heart volume

PURPOSE: To assess the risk of cardiovascular disease (CVD) after postlumpectomy irradiation restricted to tangential fields. METHODS AND MATERIALS: We assessed the incidence of CVD in 1601 patients with T1-2N0 breast cancer (BC) treated with breast tangentials in five different hospitals between 1980 and 1993. Patients treated with radiation fields other than breast tangentials and those treated with adjuvant chemotherapy were excluded. For patients with left-sided BC, maximum heart distance (MHD) was measured on the simulator films as a proxy for irradiated heart volume. Risk of CVD by laterality and MHD categories was evaluated by Cox proportional hazards regression analysis. RESULTS: Follow-up was complete for 94% of the patients, and median follow-up was 16 years. The incidence of CVD overall was 14.1%, of ischemic heart disease 7.3%, and for other types of heart disease 9.2%, with a median time to event of 10 to 11 years. The incidence of CVD was 11.6% in patients with right-sided BC, compared with 16.0% in left-sided cases. The hazard ratio associated with left-sided vs. right-sided BC was 1.38 (95% confidence interval [CI], 1.05-1.81) for CVD overall, 1.35 (95% CI, 0.93-1.98) for ischemic heart disease , and 1.53 (95% CI, 1.09-2.15) for other heart disease, adjusted for age, diabetes, and history of CVD. The risk of CVD did not significantly increase with increasing MHD. CONCLUSIONS: Patients irradiated for left-sided BC with tangential fields have a higher incidence of CVD compared with those with right-sided cancer. However, the risk does not seem to increase with larger irradiated heart volumes.