乳腺癌保乳术后全乳野中野适形调强放射治疗技术

目的：探讨乳腺癌保乳术后全乳野中野适形调强照射技术方法,并与常规全乳切线野照射技术进行剂量学对比。方法：选取22例早期乳腺癌保乳术后患者在CT模拟机下对乳腺部位行薄层定位扫描,将定位图像传输至治疗计划系统进行全乳野中野计划设计：在全乳两切线适形野的基础上挡去高剂量区部分,另设计2—4个小跳数射野以降低靶区最高剂量和调整高剂量区的范围及所在位置。处方剂量50Gy／25次,要求95％的靶区接受处方剂量;然后利用其CT模拟定位资料按照常规切线野射野方法在治疗计划上模拟常规切线野治疗计划,对野中野计划和常规射野计划进行靶区适形性、靶区均匀性和危及器官受量的比较。结果：野中野适形调强放射治疗技术的适形度、均匀性优于常规切线野照射,靶区内超过110％处方剂量的体积明显小于常规切线野技术。减少了肺组织V20的体积,降低了心脏的平均剂量和受照体积。结论：乳腺癌保乳术后全乳野中野适形调强放射治疗技术是一种有益的全乳照射技术。     

直肠癌手术后三野适形放射治疗和三射野调强放射治疗的剂量学比较

目的对比同方向布野的直肠癌三野适形放射治疗和简化三射野调强放射治疗的适形指数、靶区剂量均匀性指数、靶区平均剂量以及周围危及器官受量的差别。方法简化调强技术是指单射野的子野数目≤5个、子野面积≥10 cm2、子野照射机器跳数≥10 MU的调强放射治疗技术。10例接受术后辅助放射治疗的Ⅱ～Ⅲ期直肠癌患者,分别进行一后两侧三野适形放射治疗(3DCRT)和一后两侧三单野简化调强放射治疗(sIMRT)的计划设计,处方剂量为50Gy,利用剂量体积直方图及剂量体积直方表评价不同照射技术下靶区的适形指数、剂量均匀性指数、靶区平均剂量以及小肠、结肠、膀胱和股骨头的受量差别。结果靶区适形指数、剂量均匀性指数和靶区平均剂量均为简化三射野调强计划优于三野适形计划,小肠结肠最大剂量、各器官(小肠、结肠、膀胱、股骨头)平均剂量以及V50(股骨头为V45)均为简化调强计划低于三野适形计划,而两者计划下的各器官低剂量照射体积(V20和V10)在数值上无明显差别。结论在布野方向和单野数量相同的情况下,即使射野数较少,简化调强技术与适形技术相比仍具有更好的靶区适形度、剂量均匀性以及危及器官保护。     

早期乳腺癌保乳术后4种放疗技术的剂量参数比较

目的：比较早期乳腺癌保乳术后常规切线野（TW）、野中野调强（FIF - IMRT）、切线逆向调强（T -IMRT）和容积调强（VMAT）4种放射治疗技术的靶区和危及器官的剂量参数。方法：15例左侧早期（pT1-2 N0 M0）乳腺癌患者保乳术后接受放疗。CT 模拟定位扫描后勾画靶区和危及器官,在同一患者 CT 影像上分别做 TW、FIF - IMRT、T - IMRT 和 VMAT 4种治疗计划设计。PTV 剂量为50Gy,V47.5≥95%。4种计划的剂量限制相同。在剂量-体积直方图中读取4种计划靶区剂量的分布参数,心脏、双侧肺脏及对侧乳腺受照剂量和体积,对各参数的均数进行比较,并比较4组平均机器跳数差异。结果：4种计划都满足 V47.5≥95%。VMAT 与 T - IMRT、FIF - IMRT 和 TW 计划相比,明显提高了靶区适行指数（CI,P ﹤0.05）。VMAT、T - IMRT和 FIF - IMRT 与 TW 相比,明显改善了靶区均匀性指数（HI,P ﹤0.05）。VMAT 增加了危及器官（心脏和同侧肺脏）V 5、V10和 V20的受照射体积,但是没有增加﹥ V30的照射体积。VMAT 明显增加了右侧乳腺和右侧肺脏照射剂量（P ﹤0.05）,T - IMRT 和 FIF - IMRT 明显降低了右侧乳腺和右侧肺脏照射剂量（P ﹤0.05）。VMAT 与T - IMRT、FIF - IMRT 和 TW 相比,明显增加了机器跳数（P ﹤0.05）。结论：早期乳腺癌保乳术后放射治疗4种计划比较,VMAT 明显提高了靶区的适行性和均匀性,增加了正常组织的受照射剂量和机器跳数,延长了治疗时间。T - IMRT 和 FIF - IMRT 也提高了靶区的适行性和均匀性,降低了正常组织的受照射剂量。     

左侧乳腺癌保乳术后三种调强放疗的剂量学研究

目的比较左侧乳腺癌保乳术后3种不同射野数调强放疗方式(IMRT)的靶区及周围正常组织受照剂量的差异。方法选取8例左侧乳腺癌保乳术后患者,应用Pinnacle8.0计划系统分别设计3种不同射野数的调强计划:4野、5野、6野IMRT计划,用剂量体积直方图(DVH)和等剂量曲线评估3种计划的PTV和周围正常组织受照剂量。结果6F-IMRT靶区剂量分布最优,其剂量均匀性和适形度最好,5F-IMRT其次,4F-IMRT最差。与4F-IMRT比较,5F-IMRT和6F-IMRT的PTV最大剂量以及高剂量所包含的体积显著降低。3种计划左肺照射剂量差异较小,均不超过5%;然而心脏照射剂量4F-IMRT最小,与5F-IMRT和6F-IMRT比较,心脏V5、V10、V20、V30以及V40分别降低了42.37%、17.65%、5.87%、5.72%、23.38%和42.85%、30.84%、16.31%、6.45%、24.65%。结论左侧乳腺癌保乳放疗中,调强射野数的增加可以提高靶区PTV覆盖率、适形度和均匀性,但是也会增高左肺低剂量照射体积和平均剂量,右侧肺和心脏的受照剂量也会明显增高,故应根据患者实际情况应用合适的放疗计划进行放疗。     

早期乳腺癌保乳术后调强放疗

现行早期乳腺癌保乳术后的常规切线野放射治疗技术存在靶区内剂量不均匀的缺陷.国内外多位研究者将调强放疗(IMRT)应用于保乳术后患者,以期在提高靶区剂量均匀性、降低危及器官受量及改善美容效果方面体现出一定优势.     

左侧乳腺癌保乳术后3种放疗技术在同步推量中的剂量学研究

目的 探讨左侧乳腺癌保乳术后半弧容积动态旋转调强(VMAT)放疗、切线弧VMAT放疗和逆向调强放疗(IMRT)3种放疗技术在同步推量中的剂量学差异.方法 选取10例左侧乳腺癌保乳术后患者,使用MONACO 5.1计划系统,分别采用半弧VMAT、切线弧VMAT和IMRT三种放疗技术,处方剂量均为计划靶区(PTV)50 Gy/25 f、计划肿瘤靶区(PGTV)60 Gy/25 f,评估3种计划靶区剂量适形度指数(CI)、均匀性指数(HI)以及周围正常组织器官的受照剂量.结果 半弧VMAT的PGTV靶区CI优于IMRT(P﹤0.05).切线弧VMAT放疗技术较IMRT放疗技术降低了左侧乳腺癌保乳术后患者患侧肺组织V10的照射范围(P=0.04).切线弧VMAT放疗技术较半弧VMAT放疗技术降低了左侧乳腺癌保乳术后患者健侧肺组织V5(P﹤0.001)、V10(P=0.04)、心脏的V10(P=0.01)、Dmean(P=0.01)及健侧乳腺组织V5(P﹤0.01)的剂量范围.而IMRT放疗技术降低了左侧乳腺癌保乳术后患者健侧肺组织V5、V10的剂量范围(P﹤0.05).结论 对于左侧乳腺癌保乳术后患者的同步推量放疗,VMAT放疗技术尤其是半弧VMAT放疗技术具有更好的靶区适形性;切线弧VMAT放疗技术可以降低周围大部分正常组织器官的照射剂量.     

早期乳腺癌保乳术后全乳调强放射治疗与常规切线野放疗的剂量学比较

目的探讨早期乳腺癌保乳术后全乳调强放射治疗(intensity-modulated radiotherapy,IMRT)的剂量学优势。方法选择6例接受保乳手术的T1N0M0早期乳腺癌病例,其中左侧乳腺癌4例,右侧乳腺癌2例,应用三维调强治疗计划系统为每例患者设计常规切线野与IMRT2种全乳放射治疗计划,处方剂量均为50Gy/25次。用剂量体积直方图(dose volume histograms,DVH)来比较2种计划中计划靶体积(planning target volume,PTV)、危及器官(organs at risks,OARs)的剂量学差异。结果在2种计划中,95%PTV均接受50Gy,99%PTV均接受95%的处方剂量;但在IMRT计划组V110%(接受大于110%处方剂量体积占PTV的百分比)下降了9.1%(46.3%比37.2%,P<0.05);同侧肺的V20(至少接受20Gy照射的肺体积占同侧肺体积的百分比)下降了7.2%(26.8%比18.0%,P<0.05);同侧肺的V30下降了12.0%(23.2%比11.2%,P<0.05);4例左侧乳腺癌患者的心脏V30下降了3.8%(7.0%比3.2%,P<0.05)。结论全乳IMRT在保证靶区覆盖率的前提下,改善了靶区内剂量的均匀性,降低了危及器官的受照剂量及缩小了危及器官的照射体积,尤其是同侧肺、心脏的照射体积,降低放射性肺炎及心血管事件发生的可能。     

乳腺癌保乳术后常规切线野放疗与调强放疗剂量学比较的Meta分析

目的 探讨乳腺癌保乳术后调强放疗的优势及不足,为临床治疗提供有价值的循证医学依据。方法 计算机检索PubMed、EMBase、Science、中国知网和万方等数据库,筛选所有乳腺癌保乳术后常规切线野放疗与调强放疗的剂量学比较的文章,应用StataSE 12.0软件对满足条件的数据进行Meta分析。结果 本次研究纳入12篇文章。调强放疗较常规切线野放疗明显降低了靶区的均匀性指数HI(SMD=1.102,95%CI:0.699~1.504,P＜0.001),并明显降低了肺V20、肺V30、心脏V30及V40,差异均有统计学意义;而肺V5、肺V10及心脏V5的差异均无统计学意义。结论 与常规切线野放疗相比,乳腺癌保乳术后调强放疗使靶区分布更均匀,可明显降低高剂量区的照射靶体积,但并未减少低剂量区的照射靶体积,为临床治疗技术的选择提供依据。     

左乳腺癌术后调强放射治疗和二维切线野治疗的剂量学研究

[目的]探讨左乳腺癌术后调强放射治疗和常规二维切线野治疗的剂量学差异。[方法]用三维治疗计划系统对10例左乳腺癌术后患者分别进行调强放射治疗、常规二维切线野进行计划设计,处方剂量为50Gy,分析靶区剂量分布和心脏、肺受量。[结果]调强放射治疗靶区（PTV）剂量均匀,PTV的V50为95.12%,正常组织的低剂量区域体积大,正常组织的高剂量区域体积小。常规二维切线野PTV的V50为73.21%。[结论]调强放射治疗在正常组织耐受剂量的范围内能给临床靶区最佳的剂量分布。     

皮肤建成区效应对早期乳腺癌全乳照射治疗计划评估的影响

背景与目的:调强放疗技术(intensity-modulated radiation therapy,IMRT)可以显著提高全乳放射治疗时乳房内的剂量分布,但全乳放疗中靶体积的确定和勾画存在一定的不确定性。本研究的目的是通过对正向调强方式下全乳放射治疗计划的剂量-体积直方图的分析,定量研究皮肤建成区效应对早期乳腺癌全乳放射治疗计划评估的影响。方法:22例Ⅰ、Ⅱ期乳腺癌保乳手术后需要做全乳放疗的患者,所有患者的治疗靶区均由一名有经验的放疗医师勾画,靶区的前界直接沿皮肤的轮廓勾画,后界沿胸壁的轮廓勾画,勾画的区域为临床靶区(clinical target volume,CTV),然后在前界和后界分别收缩0.5cm,形成另一个靶区CTV1。选择最佳角度的两个相对的切线野,用正向调强方式制定治疗计划,保证重要器官肺和心脏所接受的剂量体积比、每一层面的剂量分布都满足临床放疗要求。结果:CTV超过95%处方剂量的靶区体积百分比的平均值为(89.6±3.2)%,明显低于CTV1超过95%处方剂量的靶区体积百分比(96.5±2.0)%,(P<0.001);CTV的靶区剂量均匀性指数D99-01为(14.0±2.4)Gy,明显高于CTV1的D99-01(7.3±1.6)Gy,(P<0.001)。结论:皮肤建成区效应是早期乳腺癌全乳放疗中必须考虑的重要方面之一。定量认识建成区效应对治疗计划评估的影响,是有效实现乳腺癌全乳调强放疗技术在临床开展应用的一个重要环节。在调强治疗方式下,应该以扣除表面和建成区域的临床靶区体积来进行治疗计划的评估。     

Preoperative breast MRI in early-stage breast cancer

Rapid uptake of new imaging technology is a major contributor to rising healthcare costs. Preoperative breast magnetic resonance imaging (MRI) for patients with early-stage breast cancer has dramatically increased in use without the evidence of improved outcomes compared to standard assessment and is associated with higher rates of mastectomy. A decision analytic model was developed to evaluate the impact of adding breast MRI to the preoperative evaluation of women with early-stage breast cancer who were candidates for breast-conserving therapy on patient outcomes measured in quality-adjusted life years (QALYs). Model inputs, including survival, recurrence rates, and health utilities, were obtained from a comprehensive literature review. One-way sensitivity analyses were performed to estimate threshold values for key parameters at which adding MRI would become the optimal imaging strategy over standard assessment. Preoperative MRI resulted in 17.77 QALYs compared to 17.86 QALYs with standard assessment, a decrease of 0.09 QALYs or 34?days. In sensitivity analyses, standard assessment was associated with better patient outcomes than preoperative breast MRI across all plausible probabilities for mastectomy, local recurrence, and health utilities. For routine preoperative breast MRI to become the optimal strategy, the conversion rate to mastectomy after preoperative MRI would need to be <1?% (versus the range of 3.6-33?% reported in the literature). Routine preoperative breast MRI appears to confer no advantage over the standard diagnostic evaluations for early-stage breast cancer and may lead to worse patient outcomes.     

Controversies in breast conservation treatment for breast cancer

Breast conservation treatment has become the standard treatment for early breast cancer patients, after the equivalence of mastectomy and breast conservation treatment was demonstrated in prospective, randomized trials and large retrospective studies. New questions, such as the feasibility of neoadjuvant chemotherapy in improving breast conserving rate, the appropriateness of breast conservation treatment in ductal carcinoma in situ, the effectiveness of radiation therapy in patients treated by breast conservation, and patient selection for breast conservation without radiation, are now being raised. Future work that needs to be done to answer these questions is discussed in this review.     

Glycolytic enzymes in breast cancer, benign breast disease and normal breast tissue

The activities of hexokinase, phosphofructokinase, aldolase, enolase and pyruvate kinase were studied in breast cancer tissues, in comparison to benign breast disease and normal breast tissues. The enzyme activities in breast cancer were significantly increased compared to normal and benign breast tissues (p less than 0.001). Also the increase in activity in benign disease compared to normal was statistically significant (p less than 0.001). Within the group of benign diseases, fibroadenomas could be distinguished from fibrocystic disease, the former generally showing higher activities compared to the latter (p less than or equal to 0.05). Carcinoma subgroups, classified according to their histology, could not be recognized enzymologically. In addition, isozyme composition of pyruvate kinase and enolase was studied. We did not find a significant shift towards K type pyruvate kinase expression in benign disease compared to normal breast tissues. Also fibroadenomas did not differ from fibrocystic disease. However, the amount of K type pyruvate kinase in carcinomas proved to be significantly higher in comparison to benign disease and normal breast tissues (p less than 0.001). Expression of alpha gamma-enolase in normal breast tissue was virtually absent. In benign disease only a minority of specimens did show the hybrid alpha gamma-enolase. Nearly all carcinomas had alpha gamma-enolase expression and in 20% of the carcinomas gamma gamma-enolase could be detected (so-called neuron-specific enolase). By discriminant analysis, the function giving the best discrimination compared to the histological data was based on natural logarithm aldolase and the total of gamma-enolase subunits. Contrary to expectation, the regulator enzymes of glycolysis; i.e., hexokinase, phosphofructokinase and pyruvate kinase were not included in this discriminant function. The best fit produced a 90% correct classification in both benign and malignant disease. If these findings are confirmed to a larger series, the discrimination is sufficiently strong to form the basis of a clinically useful tool.     

Mutations in normal breast tissue and breast tumours

The accumulation of mutations is a feature of all normal cells. The probability of any individual gene in any cell acquiring a mutation is, however, low. Cancer is therefore a rare disease in comparison with the number of susceptible cells. Mutations in normal tissue are stochastic, vary widely among cells and are therefore difficult to detect using standard methods because each change is so rare. If, however, a tissue such as the breast undergoes considerable clonal expansion, particularly if relatively late in life, normal tissue may have accumulated many thousands of detectable mutations. Since breast cancers are clonal and have almost certainly undergone many more cell divisions than normal cells, each tumour may have many millions of mutations, most of which are entirely innocent and some of which have accumulated in the cell of origin prior to tumorigenesis. Despite some claims to the contrary, even at normal mutation rates, clonal expansion within a tumour is quite sufficient to account for the mutations of five or six genes that are generally supposed necessary for carcinogenesis to occur. Hypermutability does, however, contribute to the pathogenesis of many cancers and, although evidence is indirect in breast cancer, may take forms such as karyotypic instability via centrosome amplification.     

倒T形切口缩乳术在乳房肥大或合并乳腺癌患者中的应用

目的探讨倒T形切口缩乳术在乳房肥大患者，特别是合并乳腺癌的患者手术中的应用及其临床意义。 方法本回顾性研究共纳入2007年10月到2017年10月分别在同济大学附属东方医院及附属同济医院乳腺外科行缩乳术的39例乳房肥大女性患者，均采用倒T形切口(内侧蒂25例，垂直蒂5例，外侧蒂9例)。其中，包括18例符合保留乳房手术指征的乳腺癌患者(内侧蒂10例，垂直蒂4例，外侧蒂4例)。术后6、12个月评价美容效果(乳腺癌患者待放射治疗结束后进行评价)。评估患者的术后并发症、满意度以及复发转移情况。 结果39例患者术后乳房外形自然、对称，明显缩小上提，乳头、乳晕血供和感觉良好，瘢痕不明显，患者满意度高。1例术后2周出现一侧乳房的乳头乳晕区坏死，经过清创换药后愈合。5例术后双侧乳头乳晕感觉减退，其中4例在术后6个月左右恢复正常感觉，1例在术后12个月恢复。5例出现术后局部乳房组织硬结，其中3例为接受过放射治疗的乳腺癌患者，二次手术切除硬结后无再次发生。3例出现瘢痕处猫耳畸形，再次局部麻醉手术修整后效果良好，3例瘢痕增粗，其余患者瘢痕正常。乳腺癌患者中有3例出现放射治疗后患侧乳房皮肤水肿，术后12个月消退。术后6个月进行了美容效果评价，极好25例，良好10例，中等4例，差0例(18例乳腺癌患者中，极好9例，良好6例，中等3例，差0例)。术后12个月的美容效果评价显示：极好25例，良好13例，中等1例，差0例(18例乳腺癌患者中，极好9例，良好8例，中等1例，差0例)。随访时间最长的1例患者(双侧乳房单纯性重度肥大)术后观察了10年，乳房外形无明显变化。全部患者术后随访15～120个月，中位随访61个月，18例乳腺癌患者均无局部复发转移。 结论对于乳房肥大，特别是合并乳腺癌的患者，采用倒T形切口缩乳术，既可切除病变，又可缩小并悬吊乳房。     

Histochemically demonstrable phosphotyrosyl-protein phosphatase in normal human breast, in benign breast diseases and in breast cancer

The activity of phosphotyrosyl-protein phosphatase enzyme was investigated by a histochemical method in the normal human breast and in breast diseases in order to evaluate its possible significance in the genesis and in the growth of benign and malignant epithelial proliferative. In normal human breast tissue only a weak enzyme activity was present. The activity was elevated in benign disease in actively proliferative lesions and in 71% of the cases of breast cancers. When enzyme activity of breast cancers was compared with the content of receptors for epidermal growth factor and insulin-like growth factor-I, no association was found. It is concluded that phosphotyrosyl-protein phosphatase is increased in actively proliferating human breast diseases. Thus the putative increase in phosphotyrosyl-proteins mediating benign and malignant epithelial proliferations is rather caused by an increase in protein-tyrosine kinase activity than by a decrease in phosphotyrosyl-protein phosphatase activity.     

Occult breast carcinoma in breast reduction specimens in European women

Breast reduction is a common surgical procedure performed by plastic and oncoplastic breast surgeons. The authors report on the incidence and management of cancer and atypical hyperplasia in breast reduction specimens from one institution over a 10-year period. All patients who underwent breast reduction surgery at Northern General Hospital, Sheffield were identified from an electronic prospective database. The histopathology reports were analyzed. Case records of all patients with significant abnormalities were retrieved and examined to identify their management and follow-up. Between October 1999 and April 2010, 1,588 patients underwent breast reduction. Nine specimens showed atypical hyperplasia (0.57%). Five cancers were detected (0.31%). Four of the five patients had normal screening mammograms 1–3 years before the reduction operation. Of these cancers, four were invasive (three lobular, one ductal) (0.25%) and one was DCIS (0.06%). A lump was felt macroscopically by the pathologist in two of the four patients with invasive cancer. The patients with DCIS did not undergo further surgery, whereas those with invasive disease underwent mastectomy (three patients) and axillary nodal staging (four patients). None of the patients with normal post-reduction breast imaging had residual cancer on histology. The incidence of occult carcinoma in breast reduction specimens is low. Patients should be counseled with regards to the possible consequences preoperatively.