Impact of dose and volume on subcutaneous fibrosis

The multifactorial genesis of radiation-induced fibrosis makes a general outline of the occurence of this late toxicity fairly unpredictable. Scientific knowledge about dose fractionation, irradiated volume, total time, conformation procedures including IMRT can help provide better treatments. Chemical and physical therapies aimed at the removal of fibrosis are still limited or under study. The system of monitoring late toxicity used by the authors is presented.     

Impact of dose and volume on rectal tolerance

Based on the successful results achieved in survival and local control with radiotherapy of prostate cancer recent studies tried to establish some models to reliably predict late rectal toxicity. In fact, the rectum, due to its location, represents an organ at risk of acute and late toxicity with the onset of acute or chronic radiation proctitis. The concept of late consequential effect has gained ground. It implies that the late damage might be a direct consequence of the acute damage. Dose-escalation studies, conformal radiotherapy (3D-CRT) and intensity modulated radiotherapy (IMRT) led to the identification of parameters, based on dose-volume histograms (DVH), able to separate patients at low and high risk of toxicity. Precise predictive dosimetric factors play a major role in the definition of the onset of toxicity. The monitoring system of late toxicity used by the authors is presented.     

Impact of dose and volume on radiation-induced mucositis

There is a relationship between a given radiation dose and the resulting biological effect in the management of head and neck cancer. Radiation mucositis represents a frequent complication in cancer chemoradiation. Its prevention and treatment are major goals in radiation therapy schedules. Critical tissues can be spared using high conformal radiation therapy (3DCRT) based on consensus guidelines for target volume. Current approaches to radiation mucositis with respect to the dose and volume impact are illustrated. The monitoring system of late toxicity used by the authors is presented.     

Impact of dose and volume on the tolerance of central nervous system

Radiotherapy still plays a major role in the treatment of brain lesions. Its end-points are not only better survival but especially better disease control that positively impacts on better quality of life. However radiotherapy is not free of both acute and late side-effects. Data on late toxicity are disappointing, for inadequate follow-up time and the absence of cards for collecting information shared by the scientific community in an attempt to acheive a common, universal language. While these treatments should be considered for palliation, the main goal is always the patient with his/her quality of life, and their toxicity should be monitored to optimize therapeutic outcomes and lower the incidence of complications. The monitoring system of late toxicity used by the authors is presented.     

上肢功能锻炼与乳腺癌术后淋巴水肿

 乳腺癌术后淋巴水肿主要是由于淋巴系统结构受损,导致淋巴系统的负荷量超过其运转能力,从而使淋巴液在组织间积聚,主要表现为患肢的肿胀、沉重感和紧绷感、疼痛以及活动受限。淋巴水肿的发生与术式、化疗、肥胖、高血压以及个体基因改变相关。为了防止淋巴水肿的发生或加重,应避免患肢过度使用,功能锻炼强调循序渐进,然而仅循序渐进是不够的,在为患者选择锻炼方法时,应该综合考虑各种方式,根据患者暴露的危险因素情况,科学的选择个性化的锻炼方案,并准确选择淋巴水肿的评价标准,实时评价效果,以达到最佳治疗的目的。     

Factors associated with increased breast cancer-related lymphedema volume

BACKGROUND: Upper limb lymphedema occurs in approximately 15-20% of women after breast cancer treatment. We analysed the factors associated with lymphedema volume. METHOD: Cross-sectional study of 807 patients with secondary arm lymphedema was performed in a single lymphology unit. Data collected included patient characteristics, characteristics of breast cancer treatment, past history of cellulitis, Body Mass Index, delay from cancer to onset of lymphedema and duration of lymphedema. Lymphedema volume was calculated for each 5-cm segment by utilizing the formula for a truncated cone. Univariate and multivariate regression models were fitted to study the factors associated with increased lymphedema volume. RESULTS: In univariate analysis, factors associated with lymphedema volume were duration of lymphedema, Body Mass Index, mastectomy, and past history of cellulitis. Treatment with anti-estrogen drugs was negatively associated with lymphedema volume (p = 0.02). In multivariate analysis, factors associated with lymphedema volume were duration of lymphedema (p < 0.001), Body Mass Index (p < 0.001), delay from cancer to onset of lymphedema (p = 0.002), mastectomy (p = 0.02) and past history of cellulitis (p = 0.011). CONCLUSION: Early diagnosis and management of lymphedema, weight control and advices to avoid cellulitis are the main controllable parameters in women to prevent severity of breast cancer-related lymphedema.     

Impact of geometric uncertainties on dose distribution during intensity modulated radiotherapy of head-and-neck cancer: the need for a planning target volume and a planning organ-at-risk volume

We assessed the effect of geometric uncertainties on target coverage and on dose to the organs at risk (OARS) during intensity-modulated radiotherapy (IMRT) for head-and-neck cancer, and we estimated the required margins for the planning target volume (PTV) and the planning organ-at-risk volume (PRV). For eight head-and-neck cancer patients, we generated IMRT plans with localization uncertainty margins of 0 mm, 2.5 mm, and 5.0 mm. The beam intensities were then applied on repeat computed tomography (CT) scans obtained weekly during treatment, and dose distributions were recalculated.The dose-volume histogram analysis for the repeat ct scans showed that target coverage was adequate (V(100) >/= 95%) for only 12.5% of the gross tumour volumes, 54.3% of the upper-neck clinical target volumes (CTVS), and 27.4% of the lower-neck CTVS when no margins were added for PTV. The use of 2.5-mm and 5.0-mm margins significantly improved target coverage, but the mean dose to the contralateral parotid increased from 25.9 Gy to 29.2 Gy. Maximum dose to the spinal cord was above limit in 57.7%, 34.6%, and 15.4% of cases when 0-mm, 2.5-mm, and 5.0-mm margins (respectively) were used for prv.Significant deviations from the prescribed dose can occur during IMRT treatment delivery for head-and-neck cancer. The use of 2.5-mm to 5.0-mm margins for PTV and PRV greatly reduces the risk of underdosing targets and of overdosing the spinal cord.     

热疗用金属热籽对放疗剂量的影响

目的 研究磁感应热疗所用于体内的金属热籽在植入机体后对放疗剂量分布产生的影响.方法 使用放疗人体仿真模型及三维治疗计划系统,通过模拟照射评估用于磁感应热疗的金属植入物处于放疗条件下对剂量分布的影响.结果 所植入的金属棒热籽材料对人体仿真组织的吸收剂量影响≤1.5%.结论 由于在组织中所植入的铁磁热籽对吸收剂量的影响很小,符合靶区剂量总不确定度<5%的要求,因此,在临床放疗处理中可以忽略不考虑其对组织的影响.     

局部晚期非小细胞肺癌三维适形放疗剂量和肿瘤体积与预后关系初探

目的探讨局部晚期肺癌大体肿瘤体积、放疗剂量与预后之间的相互关系。方法采用三维适形放疗治疗病理或细胞学证实的局部晚期（ⅢA或ⅢB）非小细胞肺癌患者79例，三维治疗计划由同一名医师勾画大体肿瘤体积（GTV）。原发病变定义为GTV-P，纵隔淋巴结定义为GTV-N，大体肿瘤体积为GTV-P加GTV-N，定义为GTV-T。对放疗剂量和GTV-T分别进行预后分层分析。结果全组1、2年生存率分别为56％、26％。GTV-T≥110cm^3组预后明显差于〈110cm^3组（P=0．031），放疗剂量〉60 Gy组生存有优于≤60 Gy组的趋势（P=0．091）。GTV-T≥110cm^3组中放疗剂量〉60 Gy亚组预后优于剂量≤60 Gy亚组（P=0．037），GTV-T〈110cm^3组中放疗剂量与预后无关。放疗剂量〉60Gy组中GTV-T大小对预后无明显影响，而≤60 Gy组中GTV-T≥110cm^3亚组预后明显差于GTV-T〈110cm^3亚组（P=0．005）。结论放疗剂量〉60 Gy可改善肿瘤体积≥110cm^3的局部晚期非小细胞肺癌的预后。     

Radiation-induced cardiovascular disease: impact of dose and volume

The radiation-induced cardiovascular pathology represents a major cause of morbidity and mortality in patients undergoing therapeutic chest irradiation. There is a broad range of clinical manifestations probably associated with dose, volume and technique of irradiation. From the assumption that prevention is the best way to manage radiation-induced cardiotoxicity, based on the pathophysiogenesis of heart structures, a number of reports of the literature are reviewed. They consider the incidence of cardiovascular disease in patients affected by Hodgkin's lymphoma and breast cancer. The dosimetric prevention is takled in terms of therapeutic procedures and doses (IMRT, 3DCRT) with particular reference to the impact on cardiotoxicity of parameters as maximum heart distance (MHD), mean lung dose (MLD), normal tissue complication probability (NTCP) and V30. The different evaluation criteria of cardiotoxicity are reported, based on the review of the major scoring scales of acute and late complications, which have been worked out in the course of time (LENT-SOMA, RTOG, CTC v.2.0 and CTC v.3.0). The monitoring system of late toxicity used by the authors is presented.     

Impact of changes in bladder and rectal filling volume on organ motion and dose distribution of the bladder in radiotherapy for urinary bladder cancer

PURPOSE: To determine the impact of filling volume changes of the urinary bladder and rectum on organ motion and dose distribution of the bladder and rectum during radical radiotherapy for bladder cancer and to calculate the internal margins to secure target coverage. METHODS AND MATERIALS: In 15 patients with muscle-invasive bladder cancer, a planning CT scan was performed with a bladder and rectal catheter, followed by three immediate CT scans with various filling of the urinary bladder and rectum. After 20 fractions, a fifth CT scan, without catherization, was performed. In each CT study, the bladder and rectum volumes were delineated and matched to the planning CT scan to measure the organ motion and calculate internal margins. These margins were compared with an isotropic standard margin of 2 cm. Dose-volume histograms were analyzed to describe the dose distribution in the bladder and rectum corresponding to various filling volumes. RESULTS: Bladder movement was most pronounced in the anterior and cranial directions. The internal margins required to cover the bladder movements due to filling of the bladder and rectum in 87% of the patients were 2.4 cm in the anterior, 1.1 cm in the posterior, 3.5 cm in the cranial, 0.5 cm in the caudal, and 1.3 cm in the lateral direction. CONCLUSION: The filling volumes of the bladder and rectum have a large impact on bladder movements, especially in the anterior and cranial directions. This should be included in the internal target volume with the introduction of anisotropic margins in conformal radiotherapy for bladder cancer.     

局部晚期鼻咽癌诱导化疗后勾画靶区对危及器官剂量及疗效影响

目的 局部晚期鼻咽癌按照诱导化疗后肿瘤体积勾画靶区安全性仍存在争议,研究局部晚期鼻咽癌诱导化疗后勾画靶区和危及器官(organs at risk,OAR),分析大体肿瘤靶区(gross tumor volume,GTV)变化对靶区适形性指数(conformity index,CI)、均匀性指数(homogeneity index,HI)和OAR剂量的影响,并观察近期疗效与不良反应,为局部晚期鼻咽癌诱导化疗后勾画靶区安全性进行临床研究.方法 收集2012-01-01-2012-12-31钦州市第一人民医院肿瘤科收治的46例局部晚期鼻咽癌患者,采用紫杉醇(paclitaxel,PTX)联合顺铂(DDP)诱导化疗2个周期,按化疗后影像勾画GTV及OAR,逆向5野调强适形(intensity-modulated radiotherapy,IMRT)设野,对2次放疗计划靶体积差值及剂量学差异行配对检验;同期DDP每周方案化疗,观察不良反应与近期疗效.结果 诱导化疗前后原发灶鼻咽部GTV(GTVnx)平均体积分别为(83.85±22.64)和(42.87±15.41) cm3,t=-5.905,P=0.001;颈淋巴结GTV(GTVnd)分别为(85.93±31.20)和(44.96±19.01) cm3,t=--5.905,P=0.001;化疗后GTVnx靶区CI(t=-2.311,P=0.021)和HI(t=-3.297,P=0.001)均好于化疗前靶区;化疗后GTVnd靶区CI(t=-2.907,P=0.001)和HI(t=-4.643,P=0.001)均好于化疗前靶区.诱导化疗后脑干、脊髓、眼球、颞叶、腮腺所受最大剂量(t=-5.905,P=0.001)和平均剂量(t=-5.834,P=0.001)降低,差异有统计学意义;3年局部控制率(local control rate,LCR)、无远处转移生存率(distantmetastasis free survival,DMFS)、无瘤生存率(disease-free survival,DFS)和总生存率(overall survival,OS)分别为91.3％、86.9％、80.4％和89.1％.诱导化疗后同步放化疗白细胞减少发生率为100.0％,Ⅲ～Ⅳ级者54.2％;口腔黏膜炎发生率为100.0％,Ⅲ级者30.4％;皮肤反应发生率为97.9％,Ⅲ级者54.2％;恶心呕吐发生率为93.5％,Ⅲ级者19.6％.结论 鼻咽癌TP方案诱导化疗后肿瘤体积缩小,按化疗后病灶勾画GTV的IMRT,CI和HI可接受;OAR最大剂量和平均剂量减小,OAR得到较好保护;诱导化疗后同步放化疗不良反应发生率高、程度略重,可耐受;近期疗效较好,远期疗效需进一步观察.     

Impact of body mass index and weight fluctuation on lymphedema risk in patients treated for breast cancer

Identifying risk factors for lymphedema in patients treated for breast cancer has become increasingly important, given the current lack of standardization surrounding diagnosis and treatment. Reports on the association of body mass index (BMI) and weight change with lymphedema risk are conflicting. We sought to examine the impact of pre-operative BMI and post-treatment weight change on the incidence of lymphedema. From 2005 to 2011, 787 newly diagnosed breast cancer patients underwent prospective arm volume measurements with a Perometer pre- and post-operatively. BMI was calculated from same-day weight and height measurements. Lymphedema was defined as a relative volume change (RVC) of ≥10 %. Univariate and multivariate Cox proportional hazards models were used to evaluate the association between lymphedema risk and pre-operative BMI, weight change, and other demographic and treatment factors. By multivariate analysis, a pre-operative BMI ≥30 was significantly associated with an increased risk of lymphedema compared to a pre-operative BMI <25 and 25- <30 (p = 0.001 and p = 0.012, respectively). Patients with a pre-operative BMI 25- <30 were not at an increased risk of lymphedema compared to patients with a pre-operative BMI <25 (p = 0.409). Furthermore, a cumulative absolute weight fluctuation of 10 pounds gained/lost per month post-operatively significantly increased risk of lymphedema (HR: 1.97, p = < 0.0001). In conclusion, pre-operative BMI of ≥30 is an independent risk factor for lymphedema, whereas a BMI of 25- <30 is not. Large post-operative weight fluctuations also increase risk of lymphedema. Patients with a pre-operative BMI ≥30 and those who experience large weight fluctuations during and after treatment for breast cancer should be considered at higher-risk for lymphedema. Close monitoring or early intervention to ensure optimal treatment of the condition may be appropriate for these patients.     

Impact of concurrent radiotherapy on chemotherapy total dose and dose intensity in patients with early breast cancer

AIMS AND BACKGROUND: A retrospective analysis was conducted to evaluate the tolerability as well as the impact of concurrent adjuvant CMF chemotherapy and radiation therapy on total CMF dose and dose intensity. METHODS: The medical records of 59 patients who had received conservative or radical surgery for breast cancer were analyzed. All patients had been assigned to 6 cycles of "1,8 CMF" adjuvant chemotherapy and concomitant radiation therapy. Total drug dose and dose intensity were calculated. Toxicity was recorded scored according to WHO criteria. RESULTS: A total of 355 cycles was administered. Fifty of 59 patients received at least 85% of the programmed chemotherapy total dose, the median value being 100% (range, 42-100). The median relative dose intensity was 0.97 (range, 0.42-1.01). Forty-four of 59 (75%) patients experienced grade 3-4 neutropenia (20 febrile neutropenia) and 29 (49%) required G-CSF support. CONCLUSIONS: This retrospective analysis showed that it is possible to give concurrent CMF and breast radiation while ensuring adequate chemotherapy total doses and dose intensities to most patients. However, G-CSF support is required in a significant proportion of patients.     

股骨头人工关节对盆腔放疗剂量分布的影响

目的 测量钴、镉、钼合金股骨头人工关节在放疗过程中次级射线引起的散射效应,以及其作为高原子序数材料对剂量分布的影响.方法 测量6、10 MV X射线入射方向距关节0.5、1.0、2.0 cm处剂量,出射方向距关节3.0、5.0、7.0 cm处剂量及距关节头部5.0、10.0 cm的剂量曲线.结果 6、10 MV X射线入射方向距关节0.5、1.0、2.0 cm处剂量偏差在0%～5%之间,随能量增加背散射效应更加显著.射线出射方向距关节3.0、5.0、7.0 cm处剂量偏差为21.6%～30.8%,射野和深度相同时随能量增加剂量偏差减少,同一能量和深度下剂量偏差随射野增加而减少.透射剂量曲线显示关节头部对剂量衰减作用极为显著.结论 在进行盆腔放疗时尽量避免射野穿过关节,或者至少降低穿越关节的射野权重.

Abstract：

Objective To study the scattering effect of Co-Cr-Mo hip prosthesis which was high Z material for patients undergoing pelvic irradiation.Methods The hip prosthesis was set in water phantom (30 cm×30 cm×30 cm), determing points were chosen on the entrance side of both 6 MV and 10 MV beams at the distance of 0.5 cm, 1.0 cm, 2.0 cm to the hip prosthesis, and also on the exit side of both 6 MV and 10 MV beams at the distance of 3.0 cm, 5.0 cm, 7.0 cm to the hip prostheses.Dose behind the hip prosthesis at depths of 5.0 cm and 10.0 cm for 6 MV and 10 MV beams are also measured.ResultsThe dose deviation on the beams′ entrance side is between 0 to 5.0%, the backscatter effect was more obviously with the higher energy beam.The dose deviation on the beams′ exit side was between 21.6%-30.8%.With the same field size and depth, dose deviation becomes smaller when the beam energy was higher;while with the same energy and depth, dose deviation becomes smaller when the field size was bigger.Dose profiles behind the head of the hip prosthesis indicate obvious attenuation of the beam.Conclusions Beam arrangements that avoid the prosthesis should be considered first or we should at least reduce the weight of the beam that pass through the prosthesis.     

Impact of drug therapy, radiation dose, and dose rate on renal toxicity following bone marrow transplantation

PURPOSE: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). METHODS AND MATERIALS: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age > or =18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. RESULTS: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. CONCLUSION: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function.