Toxicity and efficacy of three dose-fractionation regimens of intensity-modulated radiation therapy for localized prostate cancer

Outcomes of three protocols of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. A total of 259 patients treated with 5-field IMRT between 2005 and 2011 were analyzed. First, 74 patients were treated with a daily fraction of 2.0 Gy to a total of 74 Gy (low risk) or 78 Gy (intermediate or high risk). Then, 101 patients were treated with a 2.1-Gy daily fraction to 73.5 or 77.7 Gy. More recently, 84 patients were treated with a 2.2-Gy fraction to 72.6 or 74.8 Gy. The median patient age was 70 years (range, 54–82) and the follow-up period for living patients was 47 months (range, 18–97). Androgen deprivation therapy was given according to patient risk. The overall and biochemical failure-free survival rates were, respectively, 96 and 82% at 6 years in the 2.0-Gy group, 99 and 96% at 4 years in the 2.1-Gy group, and 99 and 96% at 2 years in the 2.2-Gy group. The biochemical failure-free rate for high-risk patients in all groups was 89% at 4 years. Incidences of Grade ≥2 acute genitourinary toxicities were 9.5% in the 2.0-Gy group, 18% in the 2.1-Gy group, and 15% in the 2.2-Gy group (P = 0.29). Cumulative incidences of Grade ≥2 late gastrointestinal toxicity were 13% in the 2.0-Gy group at 6 years, 12% in the 2.1-Gy group at 4 years, and 3.7% in the 2.2-Gy group at 2 years (P = 0.23). So far, this stepwise shortening of treatment periods seems to be successful.     

Utility of Smart Arc CDR for intensity-modulated radiation therapy for prostate cancer

Volumetric-modulated arc therapy (VMAT) is a widespread intensity-modulated radiation therapy (IMRT) method, however, VMAT requires adaptation of the radiation treatment planning system (RTPS) and linear accelerator (linac); these upgrades are quite expensive. The Smart Arc of Pinnacle³ (Philips), which is the software used in VMAT calculations, can select constant dose rate (CDR) mode. This approach has a low initial cost because the linac upgrade is not required. The objective of this study was to clarify the utility of CDR mode for prostate IMRT. Pinnacle³ and Clinac 21EX linac (Varian, 10 MV X-rays) were used for planning. The plans were created for 28 patients using a fixed multi-field IMRT (f-IMRT), VMAT and CDR techniques. The dose distribution results were classified into three groups: optimal, suboptimal and reject. For the f-IMRT, VMAT and CDR results, 25, 26 and 21 patients were classified as ‘optimal’, respectively. Our results show a significant reduction in the achievement rate of ‘optimal’ for a CDR when the bladder volume is <100 cm³. The total numbers of monitoring units (MUs) (average ± 1σ) were 469 ± 53, 357 ± 35 and 365 ± 33; the average optimization times were ∼50 min, 2 h and 2 h 40 min, and the irradiation times were ∼280 s, 60 s and 110 s, respectively. CDR can reduce the total MUs and irradiation time compared with f-IMRT, and CDR has a lower initial cost compared with VMAT. Thus, for institutions that do not currently perform VMAT, CDR is a useful option. Additionally, in the context of patient identification, bladder volume may be useful.     

A surveillance study of intensity-modulated radiation therapy for postoperative cervical cancer in Japan

Intensity-modulated radiation therapy (IMRT) was recently introduced to the field of gynecologic malignancies; however, its value is not yet validated. A clinical trial is in preparation to investigate the efficacy and feasibility of IMRT for postoperative cervical cancer. The object of this study was to perform a surveillance study of IMRT for post-operative cervical cancer. A questionnaire regarding the precise methods of conducting IMRT was sent to six institutions that had already introduced IMRT for post-operative cervical cancer, and the data were analyzed. Half of the institutions used static IMRT and the others used volumetric-modulated arc therapy (VMAT). Most institutions used body-immobilizing devices for patient fixation. Most institutions instructed patients to fill their bladder before undergoing planning CT or daily treatment. While one institution inserted metallic markers and another one used radio-contrast–soaked gauze to visualize the vaginal cuff, the other institutions used nothing for vaginal cuff visualization. Most institutions defined the clinical target volumes according to the Japan Clinical Oncology Group or the Radiation Therapy Oncology Group guidelines. Only one institution used a prescribed dose based on 95% of the PTV (D₉₅), while the rest used the mean dose (D_mean). This valuable information from six leading institutions will be utilized in a future prospective clinical trial.     

新型TiGRT IVS系统引导肺癌调强放射治疗摆位研究

目的:以锥形束CT(cone beam CT,CBCT)配准结果为参考,验证TiGRT IVS系统的在线校位精度,从而验证其临床有效性及可行性.方法:选择2019年10月至2020年2月在陆军军医大学第二附属医院全军肿瘤研究所放疗中心接受调强放射治疗的30例肺癌患者.首次摆位时行TiGRT IVS系统和CBCT位置验证...     

前列腺癌调强放疗重复CT模拟定位的作用

目的:探讨前列腺癌调强放疗重复CT模拟定位的作用。方法:前列腺癌调强放疗首次CT模拟定位后行CT扫描,在模拟定位工作站确定靶体积中心(等中心)做体表标记。于放射治疗4周左右进行重复CT模拟定位,扫描前用激光灯核对原等中心标记,记录等中心数值后进行CT扫描。在模拟定位工作站录入记录的原等中心数值传输至治疗计划系统,与首次CT模拟定位的图像融合后进行对比分析。结果:首次CT与重复CT图像融合后测量靶区位移的平均误差左右(RL)方向为1.9mm;头脚(SI)方向为2.8mm;前后(AP)方向为3.1mm。危及器官膀胱和直肠的最大剂量分别增加0.5～3.7Gy、0.9～5.0Gy;平均剂量分别增加0.7～4.9Gy、0.6～5.4Gy;最小剂量分别增加0.3～1.3Gy、0.6～2.8Gy。结论:前列腺癌调强放疗重复CT模拟定位便于对比分析靶区和危及器官的位移和对剂量的影响,为及时调整治疗计划提供依据。     

浅析调强放射治疗对乳腺癌保乳术后患者的影响

目的 探讨调强放射治疗对乳腺癌保乳术后患者的影响。方法 选取2015年3月—2019年10月在本院接受保乳术治疗的98例乳腺癌患者作为研究对象,按随机数字表法分为观察组与对照组,每组各49例。对照组采用常规放射治疗,观察组采用调强放射治疗。比较2组疗效、计划靶区剂量学、肌钙蛋白水平、预后情况。结果 观察组疗效总有效率为83.67%,高于对照组的65.31%,差异具有统计学意义(χ2=4.350,P=0.037);观察组计划靶区V100%、V105%分别为(9.68±0.65)%、(1.03±0.06)%,分别低于对照组的(42.02±4.87)%、(24.51±2.54)%,差异具有统计学意义(t=46.076、64.691,P值均<0.001);放疗后,观察组和对照组肌钙蛋白分别为(0.116±0.012)ng/mL、(0.260±0.019)ng/mL,分别高于放疗前的(0.059±0.010)ng/mL、(0.057±0.009)ng/mL,差异具有统计学意义(P<0.05),但观察组肌钙蛋白较对照组低,差异有统计学意义(t=44.855,P<0.001);观察组的无瘤生存率为97.96%,高于对照组的83.67%,差异具有统计学意义(χ2=4.405,P=0.036)。结论 对乳腺癌保乳术后患者辅以调强放射治疗,可提高临床疗效,调节靶区照射剂量均匀性、适应性,避免心肌及其他周围组织损伤,并提高无瘤生存率,改善预后。     

Preliminary analysis of risk factors for late rectal toxicity after helical tomotherapy for prostate cancer

The purpose of this study is to examine risk factors for late rectal toxicity for localized prostate cancer patients treated with helical tomotherapy (HT). The patient cohort of this retrospective study was composed of 241 patients treated with HT and followed up regularly. Toxicity levels were scored according to the Radiation Therapy Oncology Group grading scale. The clinical and dosimetric potential factors increasing the risk of late rectal toxicity, such as age, diabetes, anticoagulants, prior abdominal surgery, prescribed dose, maximum dose of the rectum, and the percentage of the rectum covered by 70 Gy (V70), 60 Gy (V60), 40 Gy (V40) and 20 Gy (V20) were compared between ≤ Grade 1 and ≥ Grade 2 toxicity groups using the Student''s t-test. Multivariable logistic regression analysis of the factors that appeared to be associated with the risk of late rectal toxicity (as determined by the Student''s t-test) was performed. The median follow-up time was 35 months. Late Grade 2–3 rectal toxicity was observed in 18 patients (7.4%). Age, the maximum dose of the rectum, V70 and V60 of the ≥ Grade 2 toxicity group were significantly higher than in those of the ≤ Grade 1 toxicity group (P = 0.00093, 0.048, 0.0030 and 0.0021, respectively). No factor was significant in the multivariable analysis. The result of this study indicates that the risk of late rectal toxicity correlates with the rectal volume exposed to high doses of HT for localized prostate cancer. Further follow-up and data accumulation may establish dose–volume modeling to predict rectal complications after HT.     

Longitudinal comparison of quality of life after real-time tumor-tracking intensity-modulated radiation therapy and radical prostatectomy in patients with localized prostate cancer

The purpose of this study was to compare the quality of life (QOL) in patients with localized prostate cancer (PC) after intensity-modulated radiation therapy assisted with a fluoroscopic real-time intensity-modulated radiation therapy (RT-IMRT) tumor-tracking system versus the QOL after radical prostatectomy (RP). Between 2003 and 2006, 71 patients were enrolled in this longitudinal prospective study. Each patient was allowed to decide which treatment modality they would receive. Of the 71 patients, 23 patients underwent RT-IMRT, while 48 opted for RP. No patient received neo-adjuvant or adjuvant hormone therapy. The global QOL and disease-specific-QOL were evaluated before treatment and again at 1, 3 and 5 years after treatment. There was no significant difference in the background characteristics between the two groups. The 5-year biochemical progression-free survival was 90% in the RT-IMRT and 79% in the RP group. In the RT-IMRT group, there was no significant deterioration of the global QOL or disease-specific QOL through 5 years post-treatment. In the RP group, the urinary function, sexual function, and sexual bother indicators significantly deteriorated after treatment. Urinary and sexual function was significantly better in the RT-IMRT group at 1, 3 and 5 years post-treatment compared to the RP group. RT-IMRT may be a preferable treatment for localized PC because of similar efficacy to RP but better post-treatment QOL.     

应用切片法制作静态调强挡块研究与实验

目的：通过静态调强放射新方法的研究，使得各级医院能利用现有普通放疗设备．通过增加精确定位设备和计算机放射治疗计划系统，开展静态调强放射治疗。方法：在适形放射治疗技术的基础上，提出了一种“切片”的方法，从而能利用现有简单设备制作出三维熔铅调强挡块。结果：实验和研究表明，运用该方法制作的三维熔铅调强挡块，不仅能实现靶区高剂量的形状在三维方向上与肿瘤的形状一致，而且可对照射野内剂量分布按要求的方式调整。结论：该方法简单可行，性能价格比较高，在我国各级中小医院具有良好的临床应用前景和推广意义．     

Comparison of intensity-modulated radiotherapy with the 5-field technique,helical tomotherapy and volumetric modulated arc therapy for localized prostate cancer

The outcomes of three methods of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. Between 2010 and 2018, 308 D’Amico intermediate- or high-risk patients were treated with 2.2 Gy daily fractions to a total dose of 74.8 Gy in combination with hormonal therapy. Overall, 165 patients were treated with 5-field IMRT using a sliding window technique, 66 were then treated with helical tomotherapy and 77 were treated with volumetric modulated arc therapy (VMAT). The median age of patients was 71 years. The median follow-up period was 75 months. Five-year overall survival (OS) and biochemical or clinical failure-free survival (FFS) rates were 95.5 and 91.6% in the 5-field IMRT group, 95.1 and 90.3% in the tomotherapy group and 93.0 and 88.6% in the VMAT group, respectively, with no significant differences among the three groups. The 5-year cumulative incidence of late grade ≥2 genitourinary and gastrointestinal toxicities were 7.3 and 6.2%, respectively, for all patients. Late grade ≥2 gastrointestinal toxicities were less frequent in patients undergoing VMAT (0%) than in patients undergoing 5-field IMRT (7.3%) and those undergoing tomotherapy (11%) (P = 0.025), and this finding appeared to be correlated with the better rectal DVH parameters in patients undergoing VMAT. Other toxicities did not differ significantly among the three groups, although bladder dose-volume parameters were slightly worse in the tomotherapy group than in the other groups. Despite differences in the IMRT delivery methods, X-ray energies and daily registration methods, all modalities may be used as IMRT for localized prostate cancer.     

A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer

The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan was generated by applying the optimization parameters of the original treatment plan to the anatomy of the second CT scan. The dose–volume histograms (DVHs) and dose statistics of the hybrid plan and the adapted plan were compared. The mean volume of the ipsilateral and contralateral parotid gland decreased by 6.1 cm³ (30.5%) and 5.4 cm³ (24.3%), respectively. Compared with the hybrid plan, the adapted plan provided a higher dose to the target volumes with better homogeneity, and a lower dose to the organs at risk (OARs). The Dmin of all planning target volumes (PTVs) increased. The Dmax of the spinal cord and brainstem were lower in 94% of the patients (1.6–5.9 Gy, P < 0.001 and 2.1–9.9 Gy, P < 0.001, respectively). The D_mean of the contralateral parotid decreased in 70% of the patients (range, 0.2–4.4 Gy). We could not find a relationship between dose variability and weight loss. Our two-phase adaptive IMRT protocol improves dosimetric results in terms of target volumes and OARs in patients with locally advanced NPC.     

肺癌三维适形调强放射治疗正常肺组织定义的探讨

肺脏是放射敏感器官，行胸部局部放射治疗时需要严格控制正常肺组织的受量。本文通过分析肺内大体肿瘤体积不同的两组肺癌患者三维适形调强放射治疗计划中肺组织的4种轮廓勾画方式的相关数据，探讨正常肺组织的勾画方法，以期能够更加准确地预测放射性肺损伤。     

Determining a methodology of dosimetric quality assurance for commercially available accelerator-based boron neutron capture therapy system

The irradiation field of boron neutron capture therapy (BNCT) consists of multiple dose components including thermal, epithermal and fast neutron, and gamma. The objective of this work was to establish a methodology of dosimetric quality assurance (QA), using the most standard and reliable measurement methods, and to determine tolerance level for each QA measurement for a commercially available accelerator-based BNCT system. In order to establish a system of dosimetric QA suitable for BNCT, the following steps were taken. First, standard measurement points based on tissue-administered doses in BNCT for brain tumors were defined, and clinical tolerances of dosimetric QA measurements were derived from the contribution to total tissue relative biological effectiveness factor-weighted dose for each dose component. Next, a QA program was proposed based on TG-142 and TG-198, and confirmed that it could be assessed whether constancy of each dose component was assured within the limits of tolerances or not by measurements of the proposed QA program. Finally, the validity of the BNCT QA program as an evaluation system was confirmed in a demonstration experiment for long-term measurement over 1 year. These results offer an easy, reliable QA method that is clinically applicable with dosimetric validity for the mixed irradiation field of accelerator-based BNCT.     

Dosimetric benefits of placing dose constraints on the brachial plexus in patients with nasopharyngeal carcinoma receiving intensity-modulated radiation therapy: a comparative study

This study aimed to evaluate whether placing dose constraints on the brachial plexus (BP) could provide dosimetric benefits in patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiation therapy (IMRT). Planning CT images for 30 patients with NPC treated with definitive IMRT were retrospectively reviewed. Target volumes, the BP and other critical structures were delineated; two separate IMRT plans were designed for each patient: one set no restrictions for the BP; the other considered the BP as a critical structure for which a maximum dose limit of ≤66 Gy was set. No significant differences between the two plans were observed in the conformity index, homogeneity index, maximum dose to the planning target volumes (PTVs), minimum dose to the PTVs, percentages of the volume of the PTVnx and PTVnd receiving more than 110% of the prescribed dose, or percentages of the volume of the PTVs receiving 95% and > 93% of the prescribed dose. Dose constraints significantly reduced the maximum dose, mean dose, V45, V50, V54, V60, V66 and V70 to the BP. Dose constraints significantly reduced the maximum dose to the BP, V45, V60 and V66 in both N0–1 and N2–3 disease; however, the magnitude of the dosimetric gain for each parameter between N0–1 and N2–3 disease was not significantly different, except for the V60 and V66. In conclusion, placing dose constraints on the BP can significantly decrease the irradiated volume and dose, without compromising adequate dose delivery to the target volume.     

Interfractional and intrafractional errors assessed by daily cone-beam computed tomography in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: a prospective study

This prospective study was to assess interfractional and intrafractional errors and to estimate appropriate margins for planning target volume (PTV) by using daily cone-beam computed tomography (CBCT) guidance in nasopharyngeal carcinoma (NPC). Daily pretreatment and post-treatment CBCT scans were acquired separately after initial patient setup and after the completion of each treatment fraction in 10 patients treated with IMRT. Online corrections were made before treatment if any translational setup error was found. Interfractional and intrafractional errors were recorded in the right–left (RL), superior–inferior (SI) and anterior–posterior (AP) directions. For the translational shifts, interfractional errors >2 mm occurred in 21.7% of measurements in the RL direction, 12.7% in the SI direction and 34.1% in the AP direction, respectively. Online correction resulted in 100% of residual errors ≤2 mm in the RL and SI directions, and 95.5% of residual errors ≤2 mm in the AP direction. No residual errors >3 mm occurred in the three directions. For the rotational shifts, a significant reduction was found in the magnitudes of residual errors compared with those of interfractional errors. A margin of 4.9 mm, 4.0 mm and 6.3 mm was required in the RL, SI and AP directions, respectively, when daily CBCT scans were not performed. With daily CBCT, the margins were reduced to 1.2 mm in all directions. In conclusion, daily CBCT guidance is an effective modality to improve the accuracy of IMRT for NPC. The online correction could result in a 70–81% reduction in margin size.     

Analysis of late toxicity associated with external beam radiation therapy for prostate cancer with uniform setting of classical 4-field 70 Gy in 35 fractions: a survey study by the Osaka Urological Tumor Radiotherapy Study Group

We aimed to analyse late toxicity associated with external beam radiation therapy (EBRT) for prostate cancer using uniform dose-fractionation and beam arrangement, with the focus on the effect of 3D (CT) simulation and portal field size. We collected data concerning patients with localized prostate adenocarcinoma who had been treated with EBRT at five institutions in Osaka, Japan, between 1998 and 2006. All had been treated with 70 Gy in 35 fractions, using the classical 4-field technique with gantry angles of 0°, 90°, 180° and 270°. Late toxicity was evaluated strictly in terms of the Common Terminology Criteria for Adverse Events Version 4.0. In total, 362 patients were analysed, with a median follow-up of 4.5 years (range 1.0–11.6). The 5-year overall and cause-specific survival rates were 93% and 96%, respectively. The mean ± SD portal field size in the right–left, superior–inferior, and anterior–posterior directions was, respectively, 10.8 ± 1.1, 10.2 ± 1.0 and 8.8 ± 0.9 cm for 2D simulation, and 8.4 ± 1.2, 8.2 ± 1.0 and 7.7 ± 1.0 cm for 3D simulation (P < 0.001). No Grade 4 or 5 late toxicity was observed. The actuarial 5-year Grade 2–3 genitourinary and gastrointestinal (GI) late toxicity rates were 6% and 14%, respectively, while the corresponding late rectal bleeding rate was 23% for 2D simulation and 7% for 3D simulation (P < 0.001). With a uniform setting of classical 4-field 70 Gy/35 fractions, the use of CT simulation and the resultant reduction in portal field size were significantly associated with reduced late GI toxicity, especially with less rectal bleeding.     

Eclipse计划系统NTO对直肠癌调强放疗计划的影响

目的 探讨Eclipse上的优化工具NTO（normal tissue objective）对直肠癌术后调强放疗的剂量影响。方法 随机选取20例直肠癌术后患者，每位患者均制定3组调强计划。对照组为手动NTO，其他2组分别为自动NTO和无NTO，在相同的优化条件下，自动NTO和无NTO与对照组比较靶区和危及器官剂量学参数以及机器跳数。结果 与对照组相比，自动NTO计划组适形度指数（CI）更差（t = 3.248，P < 0.05），正常组织D_mean高0.6%（t = ?3.678，P < 0.05），危及器官受量和机器跳数差异均无统计学意义（P > 0.05）；无NTO计划组CI较差（t = 16.716，P < 0.05），均匀性指数较好（t = 6.594，P < 0.05），正常组织D_mean高3.19%（t = ?8.560，P < 0.05），除小肠D_max更高外其他危及器官受量差异均无统计学意义（P > 0.05），机器跳数增加3.95%。结论 从靶区和危及器官的剂量学结果看，手动NTO和自动NTO、无NTO均能满足临床需求，但无NTO会增加靶区外热点、机器跳数和正常组织D_mean，手动NTO优势不明显，建议自动NTO用于直肠癌固定野调强放疗。