早期乳腺癌根治术后辅助放疗指征探讨

目的 探讨腋窝淋巴结阳性数为1~3个的早期乳腺癌患者根治术后辅助放疗的指征。 方法 回顾性分析根治术后并经病理证实腋窝淋巴结阳性数为1~3个的早期乳腺癌患者92例,腋窝淋巴结阳性数为1、2、3个的患者数分别为40、30、22例。其中45例接受同侧胸壁、内乳区及锁骨上淋巴引流区放疗。定义预后指数≥4分者为高危患者, < 4分者为低危患者。采用Kaplan-Meier法计算生存率,并用Logrank法进行检验。 结果 放疗患者和未放疗患者的5年生存率分别为93.5%和86.4%(χ2=3.43,P＞0.05),10年生存率分别为73.0%和56.8%(χ2=2.82,P＞0.05),局部复发率为6.7%和19.1%(χ2=4.66,P＜0.05)。低危和高危患者中未放疗患者的10年生存率分别为73.0%和56.8%(χ2=3.45,P＞0.05),局部复发率分别为11.0%和24.0%(χ2=4.64,P＜0.05)。低危和高危患者中接受放疗患者的10年生存率分别为82.0%和72.3%(χ2=4.07,P＜0.05),局部复发率分别为11.0%和5.0%(χ2=5.64,P＜0.05)。 结论 对腋窝淋巴结阳性数为1~3个的早期乳腺癌根治术后且预后指数为高危的患者,建议术后行胸壁和同侧锁骨上淋巴结辅助放疗。     

Surface and superficial dose dosimetric verification for postmastectomy radiotherapy

In patients given postmastectomy radiotherapy (PMRT), the chest wall is a very thin layer of soft tissue with a low-density lung tissue behind. Chest wall treated in this situation with a high-energy photon beam presents a high dosimetric uncertainty region for both calculation and measurement. The purpose of this study was to measure and to evaluate the surface and superficial doses for patients requiring PMRT with different treatment techniques. An elliptic cylinder cork and superflab boluses were used to simulate the lung and the chest wall, respectively. Sets of computed tomography (CT) images with different chest wall thicknesses were acquired for the study phantom. Hypothetical clinical target volumes (CTVs) were outlined and modified to fit a margin of 1–3 mm, depending on the chest wall thickness, away from the surface for the sets of CT images. The planning target volume (PTV) was initially created by expanding an isotropic 3-mm margin from the CTV, and then a margin of 3 mm was shrunk from the phantom surface to avoid artifact-driven results in the beam-let intensity. Treatment techniques using a pair of tangential wedged fields (TWFs) and 4-field intensity-modulated radiation therapy (IMRT) were designed with a prescribed fraction dose (D_p) of 180 cGy. Superficial dose profiles around the phantom circumference at depths of 0, 1, 2, 3, and 5 mm were obtained for each treatment technique using radiochromic external beam therapy (EBT) films. EBT film exhibits good characteristics for dose measurements in the buildup region. Underdoses at the median and lateral regions of the TWF plans were shown. The dose profiles at shallow depths for the TWF plans show a dose buildup about 3 mm at the median and lateral tangential incident regions with a surface dose of about 52% of D_p. The dose was gradually increased toward the most obliquely tangential angle with a maximum dose of about 118% of D_p. Dose profiles were more uniform in the PTV region for the 4-F IMRT plans. Most of the PTV region had doses >94% of D_p at depths >1 mm. The mean surface dose was about 65% of D_p for the 4-F IMRT plans. The maximum dose for the 4-F IMRT plans was <118.4% of D_p. The application of added bolus has to consider the treatment technique, tumor coverage, and possible skin reactions. For PMRT, if the chest surface and wall are treated adequately, at least 3 mm bolus should be added to the chest wall when tangential beams and 6-MV photon energy are arranged. However, when the surface and superficial regions are not high-risk areas, an IMRT plan with tangential beams and 6-MV photon energy can provide uniform dose distributions within the PTV, spare the skin reaction, and deliver sufficient doses to the chest wall at depths >1 mm.     

Acute radiation reaction and local control in breast cancer patients treated with postmastectomy radiotherapy

Background

We have investigated the variation of acute radiation reactions in medium-risk patients with postmastectomy radiotherapy with regard to a possible correlation between radiation oeaction of normal tissues and local tumor control.

Material and Methods

From 1985 through 1991, a total number of 194 patients received postmastectomy radiotherapy for breast cancer pT1-2pN0-2M0 at the University of Halle-Wittenberg. The lymphatics were irradiated by an anterior 9-MV photon field and the chest wall by an individually shaped anterior field with 9-MV electrons. Both fields received single doses of 2 Gy 5 times weekly up to a total dose of 44 Gy to the chest wall and 50 Gy to the lymphatics. All patients were routinely evaluated once weekly during radiotherapy for acute side effects by one examiner. Skin erythema was classified as mild, moderate or severe, esophagitis as being present in form of dysphagia or not and pneumonitis, if present, as asymptomatic (visible only on repeated chest X-rays) or clinically symptomatic. A differential blood count was also carried out once weekly. For this analysis, the records of all patients were retrospectively reviewed. The median follow-up at the time of analysis was 4.2 years.

Results

Of the patients, 98 (51%) had a mild, 53 (27%) moderate and 43 (22%) a severe erythema. Furthermore, 38 patients (20%) had signs of esophagitis, 13 (7%) had asymptomatic and 26 (13%) symptomatic pneumonitis. Patients with severe erythema or erythema plus esophagitis and pneumonitis had a more pronounced decrease in lymphocyte count during treatment than patients with mild erythema: the lymphocyte nadir was 0.14 vs 0.73 Gpt/l in patients with severe vs mild erythema, and 0.36 vs 0.69 Gpt/l in patients with erythema plus esophagitis plus pneumonitis vs patients with erythema only, p<0.05. Of the patients, 44 (22%) developed chronic side effects, mostly arm edema. There was no correlation between acute and late effects. An overall number of seven local recurrences (3.6%) occurred. The risk of developing a local recurrence within 5 years after treatment was 0% in patients with severe erythema or erythema plus esophagitis/pneumonitis vs 7% in patients with mild erythema only; this difference was marginally significant, p=0.055.

Conclusions

This analysis showed a trend towards better local control in patients with severe acute radiation reaction of normal tissue. The data support a recent publication by Dahl and coworkers showing a linkage between acute radiation reaction of normal tissue and tumor response in patients with preoperative radiotherapy for rectal cancer. The correlation between acute normal tissue reaction and local control might be explained by interindividual variations in the intrinsic, genetically determined radiosensitivity. However, local factors might also be involved, e. g. induction of a cytokin cascade in cases of acute reactions in normal tissues.     

早期乳腺癌保乳术后仰卧及俯卧位调强放疗的剂量学比较

目的 比较早期乳腺癌保乳术后仰卧位与俯卧位调强治疗计划靶区和危及器官的剂量学差异.方法 选取15例接受保乳术后放疗的大乳腺及乳腺下垂的左侧乳腺癌患者,分别进行仰卧位及俯卧位CT定位扫描,利用相同优化条件分别进行切线2野调强治疗计划设计.比较2种不同体位计划的靶区剂量分布、心脏、左肺及右侧乳腺受照剂量和体积,以及机器跳数的差异.结果 俯卧位调强计划适形度指数(CI)优于仰卧位计划(0.79±0.05 vs. 0.72±0.04,W=138,P<0.01),均匀性指数(HI)也优于仰卧位计划(1.09±0.01 vs. 1.12±0.02,t=-4.7,P<0.01).俯卧位计划靶区接受95%处方剂量照射的百分体积(V_95%)、最小剂量(D_min)大于仰卧位计划(t=7.1、6.4,P<0.01),平均剂量(D_mean)大于仰卧位计划(W=153,P<0.01),最大剂量(D_max)小于仰卧位计划(t=-3.6,P<0.01).仰卧位计划的右乳接受5 Gy照射的百分体积(V₅)小于俯卧位计划(W=160,P<0.01),心脏接受30 Gy照射的百分体积(V₃₀)大于俯卧位计划(t=5.4,P<0.01),心脏平均剂量(D_mean)、左肺接受20和5 Gy照射的百分体积(V₂₀、V₅)明显大于俯卧位计划(W=133、120、120,P<0.01).机器跳数间差异无统计学意义.结论 对于大乳腺及乳腺下垂乳腺癌患者,保乳术后俯卧位调强计划与仰卧位调强计划相比,靶区剂量分布更均匀,心、肺受照射剂量和体积明显减少.     

乳腺癌术后胸壁大体积复发二野和六野调强放疗剂量学比较

目的 比较乳腺癌术后胸壁大体积复发2野和6野调强放疗的计划差异.方法 对8例乳腺切除术后胸壁大体积复发病例,Pinnacle计划系统上分别对PTV进行2野调强和6野调强放疗计划设计,PTV处方剂量为50 Gy/25次(GTV后续计划补量至66～70 Gy),比较2种计划95％处方剂量PTV适形指数(CI)、均匀性指数(HI)及心脏、同侧肺剂量.结果 6野IMRT计划的CI和HI均优于2野IMRT计划,6野和2野的CI分别为(0.66±0.08)和(0.53±0.10)(t=7.99,P＜0.05),HI分别为(1.36±0.08)和(2.19±0.78)(t=9.04,P＜0.05).2个计划中肺V5、V10、V20、V35和心脏Dmax、V35、Dmean值比较差异无统计学意义.结论 乳腺癌切除术后胸壁大体积复发患者行放疗,6野静态逆向调强放疗计划靶区覆盖优于2野,而心肺受量方面无明显差异.     

快速旋转调强与五野动态调强在乳腺癌 保乳术后放疗中的剂量学比较

目的 比较乳腺癌保乳术后RapidArc计划与五野动态调强(5F-IMRT)计划的剂量学差异。方法 选择8例左侧乳腺癌保乳术后女性患者,处方剂量为50 Gy/ 25次。分别设计RapidArc计划与5F-IMRT计划。比较两种计划的靶区适形度指数、均匀性指数、靶区覆盖度和危及器官的受照剂量体积,同时比较两组计划实施时的治疗时间和机器跳数。结果 在两种计划的靶区比较中,RapidArc计划的靶区适形度指数为(0.88±0.03),高于5F-IMRT计划的(0.79±0.02)(t=8.28,P<0.05);RapidArc计划的均匀性指数为(9.01±0.73),优于5F-IMRT计划的(10.44±1.08)(t=-2.73,P<0.05)。两组计划在同侧肺受照剂量体积比较中RapidArc计划的D_mean、V₁₀、V₂₀、V₃₀小于5F-IMRT计划(t=-7.53、-7.20、-8.39、-7.80,P<0.05),但RapidArc计划中的V₅较5F-IMRT计划增加了约16% (t=5.67,P<0.05);心脏的受照剂量体积比较中RapidArc计划中的D_mean、V₅、V₁₀均高于5F-IMRT(t=10.46、28.76、5.40,P<0.05),但在RapidArc计划中心脏的V₃₀低于5F-IMRT (t=-6.12,P<0.05)。对侧肺和对侧乳腺的V₅在RapidArc计划中明显高于5F-IMRT计划 (肺:t=21.50,P<0.05;乳腺:t=5.44,P<0.05)。RapidArc计划中机器跳数减少了25%,平均治疗时间节省了60%。结论 乳腺癌保乳术后RapidArc计划与5F-IMRT计划比较提高了靶区的适形度和均匀度,减少了高剂量区的受照体积,降低了机器跳数,缩短了治疗时间,但增加了正常组织低剂量区的受照体积。     

肺癌立体定向放疗偏中心计划设计剂量学研究

目的研究不同程度的偏中心计划对肺癌立体定向放疗(SBRT)计划质量和执行准确度的影响, 为肺癌SBRT的临床计划设计提供参考。方法首先, 选取10例肺癌SBRT患者, 将计划等中心置于肿瘤质心位置, 设计等中心参考计划。将计划等中心置于偏离肿瘤质心1、3、5、8及10 cm位置, 设计偏中心计划, 共计60个, 分析这些偏中心计划相对于参考计划的剂量学差异。然后, 引入不同程度的位置误差(0～5 mm), 利用Octavius 4D高分辨率剂量验证系统, 测量这些计划的伽马通过率(GPR), 完成240次计划验证, 分析参考计划和偏中心计划的执行准确度对位置误差的鲁棒性。结果偏中心计划的剂量梯度指标略差于等中心计划, 差异无统计学意义(P>0.05)。随着偏中心距离增加, 正常肺平均剂量(MLD)和V20以及支气管Dmax略微有升高趋势。MLD在偏中心距离1、3和10 cm, 较等中心计划分别升高了0.8%、0.8%和1.9%, 差异具有统计学意义(z=-2.34～-1.99, P<0.05), V20在偏中心距离1、5和10 cm, 较等中心计划分别增加了2.0%、2.5...     

An in silico comparative dosimetric study of postmastectomy locoregional irradiation using intensity-modulated vs 3-dimensional conventional radiotherapy

An in silico dosimetric evaluation of intensity-modulated radiation therapy (IMRT) vs 3-dimensional conventional radiation therapy (3D-CRT) treatment plans in postmastectomy radiation therapy (PMRT) to the chest wall and regional lymphatics was conducted. Twenty-five consecutive patients with breast cancer referred for locoregional PMRT, stages T_2-4 with N_1-3, were planned to receive 50?Gy in 25 fractions with IMRT. Additionally, a 3D-CRT plan was generated using identical contours for the clinical target volumes (CTV), planning target volumes (PTV), and organs at risk (OAR). Treatment plans were assessed using dose-volume histogram (DVH) parameters of D₉₈, D₉₅, D₅₀, D₂, and homogeneity index for individual CTVs and PTVs. OARs evaluated were ipsilateral and contralateral lungs, heart, spinal cord, and opposite breast. Most DVH parameters pertaining to CTVs and PTVs significantly favored IMRT. V₂₀ for ipsilateral and contralateral lungs, D₃₃ of heart and maximum dose to spinal cord favored IMRT (all p?<?0.001). The mean dose to the opposite breast was significantly lesser with 3D-CRT (5.8?±?1.8?Gy vs 2.0?±?1.0?Gy, p?<?0.001). Thus, except for the mean dose to the opposite breast, the compliance to DVH constraints applied to PTV and OARs were significantly better with IMRT. At a median follow-up of 76 months (7-91), none had locoregional failure or pulmonary or cardiac morbidity. For PMRT, requiring comprehensive irradiation to both chest wall and regional lymphatics, IMRT offers superior dosimetric advantages over 3D-CRT. This was also corroborated by long-term outcomes in these patients treated with IMRT.     

基于Pinnacle3自动化计划设计模块在直肠癌调强放疗的应用研究

目的 通过比较自动化计划设计（Auto-Planning,AP）和调强放疗（IMRT）在直肠癌调强计划设计中的靶区和危及器官的剂量学差异,探讨AP在直肠癌计划设计中的优势。方法 选取10例直肠癌术后放疗病例,用Pinnacle³9.10计划系统基于同一CT图像进行IMRT和AP计划设计,比较两种不同计划的剂量体积直方图,分析靶区适形度指数（CI）、均匀性指数（HI）和危及器官受照剂量的差异。结果 AP计划中,靶区D_mean和D_min略有增加,D_maxcGy略有减小,差异有统计学意义（t=-1.36、-3.03、0.37,P<0.05）。D₂、D₉₅、D₉₈差异均无统计学意义（P>0.05）。AP计划中靶区的HI值有所降低,CI值有所提高,差异有统计学意义（t=1.24、0.10,P<0.05）。危及器官中膀胱V₄₀、V₅₀,小肠的 V₃₀、V₄₅、V₅₀,左右股骨头V₃₀、V₄₀,在AP计划与IMRT计划比较中差异有统计学意义（t=-3.21~1.02,P<0.05）。膀胱V₃₀、V₄₅,小肠V₄₀及左右股骨头V₄₅受照剂量体积均略低于IMRT计划,但差异无统计学意义（P>0.05）。结论 直肠癌AP计划能够达到比IMRT计划更好的靶区适形度,能有效降低靶区最高剂量,增加靶区最低剂量,减少热点和冷点,同时降低危及器官受照剂量,更好的保护正常组织。     

Unintended cardiac irradiation during left-sided breast cancer radiotherapy

Objective:

Cardiac irradiation during left-sided breast radiotherapy may lead to deleterious cardiac side effects. Using image guided radiotherapy, it is possible to exclude the heart from treatment fields and monitor reproducibility of virtual simulation (VS) fields at treatment delivery using electronic portal imaging (EPI). Retrospectively, we evaluate the incidence of cardiac irradiation at VS and subsequent unintended cardiac irradiation during treatment.

Methods:

Patients receiving left-sided radiotherapy to the breast or chest wall, treated with a glancing photon field technique during a four-month period, were included. VS images and EPIs during radiotherapy delivery were visually assessed. The presence of any portion of the heart within the treatment field at VS or during treatment was recorded. Central lung distance and maximum heart distance were recorded.

Results:

Of 128 patients, 45 (35.1%) had any portion of the heart within the planned treatment field. Of these, inclusion of the heart was clinically unavoidable in 25 (55.6%). Of those with no heart included in the treatment fields at VS, 41 (49.4%) had presence of the heart as assessed on EPI during treatment.

Conclusion:

Unintended cardiac irradiation during left-sided breast radiotherapy treatment occurs in a sizeable proportion of patients.

Advances in knowledge:

Despite the use of three-dimensional computed tomography simulation and cardiac shielding, sizeable proportions of patients receiving left-sided breast cancer radiotherapy have unintended cardiac irradiation.Post-operative radiotherapy is indicated following breast-conserving surgery and following mastectomy in those with high-risk features [1]. Following breast-conserving surgery, radiotherapy to residual breast tissue has been shown to lead to a significant reduction in local recurrence rates, with an associated reduction in breast cancer-specific mortality demonstrated in more recent analyses [2]. For women at higher risk of recurrence following mastectomy, such as those with heavily node-positive disease, post-operative radiotherapy also reduces local recurrence and improves survival [2]. The acute toxicities of breast or chest wall radiotherapy are well documented and usually resolve within the first few months following completion of treatment [3,4]. Over recent years, there has been an increasing awareness of the late effects of radiotherapy, particularly when treatment is given in an adjuvant or radical setting and long-term patient survival is anticipated [5,6].Data from randomised trials have demonstrated excess mortality from cardiovascular disease among women treated with radiotherapy for early breast cancer, particularly where local nodal areas were irradiated [2,7]. A population-based study has also reported a significant association between fatal myocardial infarction and left-sided adjuvant radiotherapy given post lumpectomy [8]. During post-operative radiotherapy for breast cancer, cardiac musculature and its associated vasculature may be irradiated directly or indirectly via scatter radiation. The risk of cardiovascular disease was shown to be higher in those patients irradiated for a left-sided breast cancer, although there is a suggestion that this increased risk may not be present with newer radiotherapy techniques [2,9–11]. Other studies report that late cardiotoxicity still occurs with modern therapy when patient follow-up is over 10 years [12].The total dose to cardiac structures appears to affect the degree of risk, although there is uncertainty as to the identity of the critical structures. Animal studies have shown the development of atherosclerotic changes in irradiated cardiac vessels, with human post-mortem examinations revealing similar changes, along with increased fibrotic change within cardiac tissue [8,13]. The left anterior descending artery may be important as it provides the blood supply to a significant area of myocardium, and ongoing studies are considering how the dose to this, and to the other main coronary arteries, affects risk of later cardiac events [14]. The α/β ratio for late effects on the coronary vessels has not as yet been fully determined, and the underlying radiobiology of heart damage remains poorly understood [15]. In terms of cardiac function, the most significant pathological process is believed to be myocardial damage resulting from diffuse interstitial fibrosis secondary to a cytokine-driven acute inflammatory response to radiation-induced endothelial damage [16]. Fibrotic change reduces cardiac compliance, and it may impair conduction pathways and lead to valvular dysfunction. Radiation induced atherosclerosis appears to be similar to atherosclerotic changes seen in the unirradiated population, except that it may occur at a younger age and in individuals without risk factors typical for the development of coronary artery disease [17].Although the current gold standard for calculating cardiac dose is three-dimensional computed tomography (CT) radiotherapy planning with manual contouring of cardiac structures, this facility is not yet universally available in UK radiotherapy centres. Taylor et al [14] recently demonstrated that maximum heart distance (MHD) measured on simulation images provides a reliable surrogate for estimating dose to cardiac tissue. Using visual assessment and measurement of MHD, we retrospectively evaluate the incidence and extent of any cardiac irradiation at virtual simulation (VS). As the volume of heart included in radiation fields may change during treatment owing to factors such as patient relaxation and interfractional and intrafractional variation in respiration, we also evaluate any subsequent unintended cardiac irradiation during treatment using visual assessment and MHD measurements from electronic portal imaging (EPI).     

Comparative dosimetric study of two strategies of intensity-modulated radiotherapy in nasopharyngeal cancer

This study compared the target volume coverage and normal tissues sparing of simultaneous integrated boost (SIB-IMRT, 1-phase) and sequential-IMRT (2-phase) for nasopharyngeal carcinoma (NPC). Fourteen consecutive patients with newly diagnosed primary NPC were enrolled in this study. The CT images were transferred to a commercial planning system for structural delineation. The gross tumor volume (GTV) included gross nasopharyngeal tumor and involved lymph nodes of more than 1-cm diameter. The clinical target volume (CTV) modeled two regions considered to represent different risks. CTV1 encompassed the GTV with 5–10-mm margin of adjacent tissues. CTV2 encompassed ipsilateral or contralateral elective nodal regions at risk of harboring microscopic tumor. A commercial IMRT treatment planning system (Eclipse Version 7.1) was used to provide treatment planning. Seven fixed-gantry (0°, 50°, 100°, 150°, 210°, 260°, 310°) angles were designated. The 14 patients were treated with sequential-IMRT, and treatment was then replanned with an SIB strategy to compare the dosimetric difference. For the sequential strategy, the dose delivered to CTV1/CTV2 in the first course was 54 Gy (1.8 Gy × 30 Fr); while CTV1 was boosted by an additional 16.2 Gy (1.8 Gy × 9 Fr) in the second course. For SIB-IMRT, the dose prescribed to CTV1 was 69.7 Gy (2.05 Gy × 34 Fr); 56.1 Gy was given to CTV2 (1.65 Gy × 34 Fr). A statistical analysis of the dose-volume-histogram of target volumes and critical organs was performed. Paired Student’s t-test was used to compare the dosimetric differences between the two techniques. The mean dose to CTV1 was 101.7 ± 2.4% and 102.3 ± 3.1% of the prescribed dose for SIB-IMRT and sequential-IMRT, respectively. The mean CTV2 dose was 109.8 ± 4.7% of the prescribed dose for SIB-IMRT and 112.6 ± 6.0% of the prescribed dose for sequential-IMRT. The maximal dose to the spinal cord was 4489 ± 495 cGy and 3547 ± 767 cGy for SIB and sequential-IMRT (p = 0.0001), respectively. The maximal dose to brain stem was significantly higher using SIB technique (5284 ± 551 cGy) than sequential-IMRT (4834 ± 388 cGy) (p = 0.0001). The mean dose to the parotid gland and ear apparatus was significantly lower using SIB-IMRT. The mean dose to the right/left parotids was 2865 ± 320 cGy/2903 ± 429 cGy and 3567 ± 534 cGy/3476 ± 489 cGy for SIB and sequential-IMRT, respectively (p = 0.0001). Target coverage was the same for both techniques; the dose distribution in the elective nodal area with SIB was superior to that with sequential-IMRT. SIB-IMRT provides better sparing of parotid gland and inner ear structures. Extra caution should be taken when applying SIB-IMRT since critical organs close to the boost volume may receive higher doses.     

Comparative dosimetric study of two strategies of intensity-modulated radiotherapy in nasopharyngeal cancer

This study compared the target volume coverage and normal tissues sparing of simultaneous integrated boost (SIB-IMRT, 1-phase) and sequential-IMRT (2-phase) for nasopharyngeal carcinoma (NPC). Fourteen consecutive patients with newly diagnosed primary NPC were enrolled in this study. The CT images were transferred to a commercial planning system for structural delineation. The gross tumor volume (GTV) included gross nasopharyngeal tumor and involved lymph nodes of more than 1-cm diameter. The clinical target volume (CTV) modeled two regions considered to represent different risks. CTV1 encompassed the GTV with 5–10-mm margin of adjacent tissues. CTV2 encompassed ipsilateral or contralateral elective nodal regions at risk of harboring microscopic tumor. A commercial IMRT treatment planning system (Eclipse Version 7.1) was used to provide treatment planning. Seven fixed-gantry (0°, 50°, 100°, 150°, 210°, 260°, 310°) angles were designated. The 14 patients were treated with sequential-IMRT, and treatment was then replanned with an SIB strategy to compare the dosimetric difference. For the sequential strategy, the dose delivered to CTV1/CTV2 in the first course was 54 Gy (1.8 Gy × 30 Fr); while CTV1 was boosted by an additional 16.2 Gy (1.8 Gy × 9 Fr) in the second course. For SIB-IMRT, the dose prescribed to CTV1 was 69.7 Gy (2.05 Gy × 34 Fr); 56.1 Gy was given to CTV2 (1.65 Gy × 34 Fr). A statistical analysis of the dose-volume-histogram of target volumes and critical organs was performed. Paired Student’s t-test was used to compare the dosimetric differences between the two techniques. The mean dose to CTV1 was 101.7 ± 2.4% and 102.3 ± 3.1% of the prescribed dose for SIB-IMRT and sequential-IMRT, respectively. The mean CTV2 dose was 109.8 ± 4.7% of the prescribed dose for SIB-IMRT and 112.6 ± 6.0% of the prescribed dose for sequential-IMRT. The maximal dose to the spinal cord was 4489 ± 495 cGy and 3547 ± 767 cGy for SIB and sequential-IMRT (p = 0.0001), respectively. The maximal dose to brain stem was significantly higher using SIB technique (5284 ± 551 cGy) than sequential-IMRT (4834 ± 388 cGy) (p = 0.0001). The mean dose to the parotid gland and ear apparatus was significantly lower using SIB-IMRT. The mean dose to the right/left parotids was 2865 ± 320 cGy/2903 ± 429 cGy and 3567 ± 534 cGy/3476 ± 489 cGy for SIB and sequential-IMRT, respectively (p = 0.0001). Target coverage was the same for both techniques; the dose distribution in the elective nodal area with SIB was superior to that with sequential-IMRT. SIB-IMRT provides better sparing of parotid gland and inner ear structures. Extra caution should be taken when applying SIB-IMRT since critical organs close to the boost volume may receive higher doses.     

直肠癌调强放疗计划中六维随机摆位误差的剂量学影响研究

目的 设计一种软件将随机六维摆位误差引入到直肠癌调强放疗(IMRT)计划中,并评估其剂量学影响。方法 随机选取21例直肠癌IMRT计划作为参考计划(单次剂量 2 Gy, 共50 Gy;PTV为CTV均匀外扩5 mm)。对参考计划的每个分次,通过调整射野几何参数的方法引入随机生成的六维摆位误差,并重新完成剂量计算。再将各分次剂量累加后得到存在摆位误差情况下的总剂量分布。基于美国瓦里安Eclipse脚本应用程序接口(ESAPI)开发能够自动完成上述流程的治疗模拟软件,将服从两种预设分布[分布1:平移误差服从N(0,4²),旋转误差服从N(0,2²);分布2:平移误差服从N(0,2²),旋转误差服从N(0,1²)]的六维摆位误差引入参考计划,并评估剂量学影响。结果 参考计划、误差分布1和误差分布2情况下,CTV的D_min分别为(49.4±0.41)、(47.56±0.76)和(49.17±0.64)Gy;CTV的D_98%分别为(50.23±0.07)、(49.98±0.10)和(50.27±0.09)Gy;主体靶区(靶区除去边缘后的内核部分)D_98%为(50.25±0.08)、(50.42±0.13)和(50.33±0.10)Gy;边缘靶区D_98%为(50.22±0.10)、(49.88±0.11) 和(50.26±0.10)Gy。另外,相比参考计划,误差分布1和2的情况下,膀胱和股骨头平均受量的变化差异均无统计学意义(P>0.05),剂量分布的适形指数虽有微弱降低,但临床意义有限。结论 本方法及据此开发的治疗模拟软件可以根据需要将服从不同分布的六维摆位误差引入到直肠癌IMRT计划中,并给出总体剂量学变化情况。     

乳腺癌改良根治术后放疗两种固定方式在锁骨上下区摆位误差的比较

目的 比较使用头颈肩热塑网罩和颈胸一体热塑体膜固定的乳腺癌改良根治术后放疗患者锁骨上下区的摆位误差。 方法 回顾性分析2019年6至12月中国医学科学院北京协和医学院肿瘤医院放疗科收治的40例女性乳腺癌改良根治术后患者[中位年龄46（29~68）岁]的锁骨上下区靶区的锥形束CT（CBCT）图像,其中19例使用头颈肩热塑网罩进行体位固定（头颈肩网罩组,128次CBCT图像）,21例使用颈胸一体架膜进行体位固定（颈胸一体膜组,143次CBCT图像）。分析2组患者锁骨上下区的摆位误差,并分别测量肩锁关节的位置移动幅度ΔX、ΔY、ΔZ和三维空间位移d。应用公式计算临床靶区至计划靶区（PTV）的外放边界值。将所有患者分成体重指数（BMI）<24 kg/m2组（13例,86次CBCT扫描）和BMI≥24 kg/m2组（27例,185次CBCT扫描）,分析比较2组的摆位误差。2组之间的比较采用独立样本t检验。 结果 头颈肩网罩组和颈胸一体膜组在锁骨上下区的平移摆位误差分别为左右方向：（1.78±2.40） mm和（2.26±1.91） mm（t=0.687,P=0.496）、头脚方向：（2.88±2.44） mm和（2.29±1.89） mm（t=2.249,P=0.030）、腹背方向：（2.48±1.79） mm和（1.66±2.00） mm（t=0.998,P=0.325）;在矢状面的旋转摆位误差分别为（0.91±0.61）度和（0.67±0.53）度,差异有统计学意义（t=3.555,P=0.001）。头颈肩网罩组和颈胸一体膜组在肩锁关节的位置移动幅度ΔX、ΔY、ΔZ的平均值分别为3.65、4.61、3.11 mm和2.32、1.97、1.63 mm,三维空间位移d的平均值分别为7.36 mm和4.03 mm。头颈肩网罩组和颈胸一体膜组锁骨上下区在左右方向、头脚方向和腹背方向的PTV外放边界值分别为6.1、8.9、7.5 mm和7.0、7.0、5.5 mm。BMI<24 kg/m2组和BMI≥24 kg/m2组患者在3个方向的平移和旋转摆位误差的差异均无统计学意义（t=−1.103~0.938,均P>0.05）。 结论 对于乳腺癌改良根治术后行锁骨上下区放疗的患者,相比头颈肩网罩固定,使用颈胸一体膜固定在头脚方向的摆位误差更小,而且对肩锁关节的体位固定效果更优。     

Postmastectomy radiotherapy for left-sided breast cancer patients: Comparison of advanced techniques

Postmastectomy radiotherapy (PMRT) has been shown to improve the overall survival for invasive breast cancer patients, and many advanced radiotherapy technologies were adopted for PMRT. The purpose of our study is to compare various advanced PMRT techniques including fixed-beam intensity-modulated radiotherapy (IMRT), non-coplanar volumetric modulated arc therapy (NC-VMAT), multiple arc VMAT (MA-VMAT), and tomotherapy (TOMO). Results of standard VMAT and mixed beam therapy that were published by our group previously were also included in the plan comparisons. Treatment plans were produced for nine PMRT patients previously treated in our clinic. The plans were evaluated based on planning target volume (PTV) coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP) of pneumonitis, lifetime attributable risk (LAR) of second cancers, and risk of coronary events (RCE). All techniques produced clinically acceptable PMRT plans. Overall, fixed-beam IMRT delivered the lowest mean dose to contralateral breast (1.56 ± 0.4 Gy) and exhibited lowest LAR (0.6 ± 0.2%) of secondary contralateral breast cancer; NC-VMAT delivered the lowest mean dose to lungs (7.5 ± 0.8 Gy), exhibited lowest LAR (5.4 ± 2.8%) of secondary lung cancer and lowest NTCP (2.1 ± 0.4%) of pneumonitis; mixed beam therapy delivered the lowest mean dose to heart (7.1 ± 1.3 Gy) and exhibited lowest RCE (8.6 ± 7.1%); TOMO plans provided the most optimal target coverage while delivering higher dose to OARs than other techniques. Both NC-VMAT and MA-VMAT exhibited lower values of all OARs evaluation metrics compare to standard VMAT. Fixed-beam IMRT, NC-VMAT, and mixed beam therapy could be the optimal radiation technique for certain breast cancer patients after mastectomy.     

Application of hypoglossal nerve constraint in definitive radiotherapy for nasopharyngeal carcinoma: A dosimetric feasibility study

Purpose: Radiation-induced hypoglossal nerve palsy is an infrequent but debilitating late complication after definitive radiotherapy for head and neck cancers. D1cc < 74 Gy (equivalent dose in 2 Gy fractions, EQD2) has been proposed as a potential dose constraint that limits 8-year palsy risk to < 5%. This study sets to perform detailed dosimetric assessments on the applicability of this novel dose constraint in advanced nasopharyngeal carcinoma (NPC). Materials and methods: This is a retrospective single-institution dosimetry study. NPC radiotherapy plans were identified from an institutional database, with an aim to select 10 eligible cases. Bilateral hypoglossal nerves were retrospectively contoured following a standard atlas. Cases with either one, or both, hypoglossal nerves D1cc exceeded 74 Gy EQD2 were included. Dosimetry of hypoglossal nerves, planning target volumes (PTV) and normal structures before and after application of the new hypoglossal nerve constraint were compared and analyzed. Results: Ten NPC cases were replanned. All hypoglossal nerve contours overlapped with high-dose PTV, predominantly at regions of gross nodal diseases. D1cc in 15 out of 20 hypoglossal nerves exceeded 74G y EQD2 at initial plans. All nerves fulfilled the pre-specified constraint of 74Gy EQD2 after re-plan. Median hypoglossal nerve D1cc reduced from 74.8Gy (range, 74.1 to 77.4Gy) to 73.5Gy (range, 72.4 to 74.0Gy) (p < 0.001), corresponded to a projected reduction in 8-year palsy risk from 5%-14% to 3%-5%. PTV V100 was maintained above 95% in all cases. Dose increments in near-maximum (D2) and decrements in near-minimum (D98) were < 1 Gy. Safety dosimetric parameters of standard head and neck organs-at-risk showed no significant changes. Conclusions: Hypoglossal nerve D1cc < 74 Gy EQD2 is a dosimetrically feasible constraint in definitive radiotherapy for NPC. Tumor target coverage and normal organ dosimetry were not compromised with its usage. Its routine application should be considered in definitive radiotherapy for head and neck cancers.     

Use of tomotherapy in treatment of synchronous bilateral breast cancer: dosimetric comparison study

Objective:

Synchronous malignancy in both breasts is a rare incidence. The present study aims at dosimetric comparison of conventional bitangential radiotherapy (RT) technique with conventional [field-in-field (FIF)] and rotational [Helical TomoTherapy® and TomoDirect™ (TD); Accuray Inc., Sunnyvale, CA] intensity-modulated RT for patients with synchronous bilateral breast cancer (SBBC).

Methods:

CT data sets of 10 patients with SBBC were selected for the present study. RT was planned for all patients on both sides to whole breast and/or chest wall using the above-mentioned techniques. Six females with breast conservation on at least one side also had a composite plan along with tumour bed (TB) boost using sequential electrons for bitangential and FIF techniques or sequential helical tomotherapy (HT) boost (for TD) or simultaneous integrated boost (SIB) for HT.

Results:

All techniques produced acceptable target coverage. The hotspot was significantly lower with FIF technique and HT but higher with TD. For the organs at risk doses, HT resulted in significant reduction of the higher dose volumes. Similarly, TD resulted in significant reduction of the mean dose to the heart and total lung by reducing the lower dose volumes. All techniques of delivering boost to the TB were comparable in terms of target coverage. HT-SIB markedly reduced mean doses to the total lung and heart by specifically lowering the higher dose volumes.

Conclusion:

This study demonstrates the cardiac and pulmonary sparing ability of tomotherapy in the setting of SBBC.

Advances in knowledge:

This is the first study demonstrating feasibility of treatment of SBBC using tomotherapy.Breast cancer is the most common malignancy amongst females in the world, including Indian females.¹ Cancer in both breasts is an uncommon presentation. Incidence of bilateral breast cancer (BBC) has been reported in the range of 1.4–11.8% with the majority being metachronous cancer.^2,3 Depending upon various definitions adopted by authors, synchronous BBC (SBBC) accounts for approximately 0.4–2.8% of all breast cancers.^4,5 Whether bilaterality confers worse prognosis or similar prognosis is yet to be conclusively determined. Some studies have indicated that there is no difference in survival between the unilateral vs BBC patient groups, while other studies claim that bilateral carcinoma significantly reduces survival.^6,7 Treatment in patients with BBC is similar to that in patients with unilateral breast cancer wherein adjuvant radiotherapy (RT) forms an integral part of the breast conservation algorithm. The safety of breast conservation surgery (BCS) for SBBC has been documented in literature.^8,9 Adjuvant RT for breast cancer typically includes whole breast irradiation after lumpectomy or chest wall irradiation after mastectomy with or without regional nodal irradiation. This is accomplished using conventional bitangential portals that include part of the anterior chest wall adjacent to the RT target.^10–12 RT delivery in cases of SBBC is even more complex owing to multiple field junctions, which results in heterogeneous dose distributions as well as significantly higher irradiation volume of organs at risk (OARs) such as the lungs and heart.The reported incidence of radiation pneumonitis (RP) varies from 0% to 80% depending upon the radiation technique, length of follow-up, imaging modality used and the end point chosen.^13–16 Although symptomatic RP is a rare clinical complication for unilateral breast cancer, it has a potential detrimental effect of reducing the normal functional reserve and should be taken into consideration given the long life expectancy of patients and higher volume of irradiation owing to bilaterality in patients with SBBC. The risk and severity of RP is influenced by various therapy-related (volume of incidentally irradiated lung, region of irradiated lung, radiation dose, fractionation and concomitant use of systemic agents, particularly paclitaxel) and patient-related factors (age, pre-existing lung disease, poor pulmonary function, smoking habits, genetic predisposition). The most significant amongst these include patient age, locoregional RT, reduced pre-RT pulmonary reserve and concomitant tamoxifen use with adjuvant RT.^17–19 These factors correlate with various dosimetric indices [V₂₀, D₂₅, mean lung dose (MLD)] that predict the risk of RP.²⁰Similarly, the toxic effect of radiation on the heart has been well documented. The long-term risk of ischaemic heart disease following breast RT has been correlated with the mean heart dose, maximum heart distance and various dosimetric parameters (V₂₀, V₃₀ and V₄₀). Moreover, several patient-related risk factors (body mass index, diabetes mellitus, dyslipidaemia, tobacco/alcohol consumption, prior heart disease) and systemic agents (anthracyclines, trastuzumab, tamoxifen) modify the risk of radiation-induced cardiac toxicity.^21,22 Patients with BBC receive a higher radiation dose to the heart (owing to scatter radiation from the right side) and would be at increased risk of radiation-induced cardiac toxicity.²³Although techniques of delivering RT have improved considerably for various sites in past two decades, the technique of delivering RT to the breast or chest wall, unilateral or bilateral, has not changed much. Various other methods have been used to deliver RT to the breast and/or the chest wall for SBBC across the world, such as electron arc therapy, or static or rotational intensity-modulated RT (IMRT), but none has been compared with conventional bitangential RT.^24,25Helical TomoTherapy® (HT) (Accuray Inc., Sunnyvale CA) is a radiation delivery modality that delivers an intensity-modulated fan beam using a 6-MV linear accelerator mounted on a ring gantry that rotates around the patient as he/she advances slowly through the gantry bore.²⁶ Dosimetric data regarding the use of HT in breast cancer treatment have resulted in equivocal results, not only in the context of target coverage and homogeneity but in the sparing of the heart and lungs as well. Although HT has been studied in the context of partial breast irradiation, whole breast irradiation and locoregional nodal irradiation,^27–30 fewer data are available on the dosimetry and feasibility of HT in the context of SBBC requiring bilateral adjuvant radiation with or without simultaneous integrated boost (SIB) of the tumour bed (TB).TomoDirect™ (TD) (Accuray Inc.) is a static or non-rotational extension of HT, which is also referred to as TomoTherapy®. In this application of TomoTherapy, the patient is translated craniocaudally through fixed gantry positions with simultaneous beam modulation. Up to 12 coplanar fixed beams can be used for dose optimization and target coverage. Similar to HT, dosimetric and clinical data are also available with TD in both, three-dimensional conformal RT (3DCRT) and/or IMRT mode for treatment of unilateral breast cancer treatment.^28,31–33 However, no data are available on the dosimetry and feasibility of TD in the context of SBBC.In our study, we aimed to compare conventional bitangential RT with conventional IMRT and two techniques of tomotherapy, namely HT and TD dosimetrically in the context of SBBC.     

头颈部肿瘤调强放射治疗后甲状腺功能减退的临床参数和剂量影响因素

目的 探讨头颈部肿瘤患者接受调强放射治疗（IMRT）后出现甲状腺功能减退（HT）与患者临床特征参数、剂量体积直方图（DVH）参数的相关性。方法 收集28例接受头颈部IMRT（颈部照射剂量 ≥ 40 Gy）联合化疗的肿瘤患者资料。治疗前后及随访观察中监测血清促甲状腺激素（TSH）、游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）。原发性HT定义为血清TSH高于正常值的上限伴或不伴有FT3/FT4的降低。基于放疗计划系统DVH,记录每一位患者甲状腺体积（TV）、甲状腺平均照射剂量（MTD）、最大点剂量（D_max）、甲状腺接受≥5~50 Gy的相对体积（表示为V_x,x=5~50,5 Gy为间隔）。回顾性分析患者年龄、性别、化疗、TV、MTD、D_max及各DVH参数与HT的相关性。 结果 全组患者治疗前血清TSH、FT3和FT4中位数分别为1.51 μU/ml、5.38和18.57 pmol/L。中位随访15个月（3~57月）,14例（50.0%）患者出现HT,出现HT的中位时间为放疗后8个月（2~23月）。患者首次监测发现HT时间点的TSH、FT3和FT4中位数分别为7.48 μU/ml（4.67~60.11 μU/ml）、4.05 pmol/L（0.40~5.77 pmol/L）和12.32 pmol/L（4.12~21.25 pmol/L）,HT患者的TSH较治疗前明显升高（P<0.01）。HT患者的TV中位数为17.76 cm³,显著低于未出现HT患者的20.21 cm³（Z=-2.154,P<0.05）。单因素分析显示患者年龄和V₄₀与HT的发生风险相关（χ²=11.340、4.102,OR=30.0、9.17,P<0.05）。多因素分析证实患者年龄、V₄₀均是HT的独立影响因素（OR=34.7、6.13,P<0.05）。结论 头颈部肿瘤患者IMRT后出现HT伴随TSH的显著增高。低龄、甲状腺体积较小的患者,甲状腺V₄₀大于80%是发生HT的高风险因素。