图像引导对宫颈癌放疗中直肠、膀胱照射剂量的影响

目的 分析宫颈癌根治性外照射图像引导与否对直肠和膀胱受照剂量的影响,探讨IGRT技术合理应用的模式。方法 选取2012—2016年于陆军总院行HT的宫颈癌患者20例。每次治疗前均进行MVCT扫描,应用MVCT图像在HT的自适应模块上进行剂量重建,得到当次的受量,并模拟出该次无图像引导下的受量;将各单次剂量分布和对应的融合CT图像传输至形变软件MIM6.0中进行剂量叠加,得到总照射剂量。对比图像引导与否对直肠及膀胱受量和体积的影响。结果 无图像引导的Plan-2的直肠和膀胱受量均高于图像引导下的Plan-1,其中直肠Dmax、V50及膀胱V50均不同(P=0.040、0.000、0.047);分次间初次治疗的Dmax和V50及治疗第13~21次的直肠V50与Plan-1比差异有统计学意义(P=0.047、0.037,P=0.009、0.017、0.028),首次及21~23次放疗的膀胱Vmax、V50与Plan-1比接近有统计学意义(P=0.061、0.053,P=0.072、0.058)。结论 图像引导可以降低直肠和膀胱的受照剂量及体积,尤其是直肠从图像引导获益更大;建议外照射半量左右(13次左右),肿瘤退缩明显时段,重新定位修改治疗计划;对于难以实现全程图像引导的情况下,进行选择性的图像引导,也可以达到有效地降低直肠和膀胱损伤发生的效果。     

Comparison of conventional and CT-based planning for intracavitary brachytherapy for cervical cancer: target volume coverage and organs at risk doses

Background

Hepatocellular carcinoma (HCC), a major cause of cancer death in China, is preceded by chronic hepatitis and liver cirrhosis (LC). Although hepatitis B virus (HBV) has been regarded as a clear etiology of human hepatocarcinogenesis, the mechanism is still needs to be further clarified. In this study, we used a proteomic approach to identify the differential expression protein profiles between HCC and the adjacent non-tumorous liver tissues.

Methods

Eighteen cases of HBV-related HCC including 12 cases of LC-developed HCC and 6 cases of chronic hepatitis B (CHB)-developed HCC were analyzed by two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), and the results were compared to those of paired adjacent non-tumorous liver tissues.

Results

A total of 17 differentially expressed proteins with diverse biological functions were identified. Among these, 10 proteins were up-regulated, whereas the other 7 proteins were down-regulated in cancerous tissues. Two proteins, c-Jun N-terminal kinase 2 and ADP/ATP carrier protein were found to be up-regulated only in CHB-developed HCC tissues. Insulin-like growth factor binding protein 2 and Rho-GTPase-activating protein 4 were down-regulated in LC-developed and CHB-developed HCC tissues, respectively. Although 11 out of these 17 proteins have been already described by previous studies, or are already known to be involved in hepatocarcinogenesis, this study revealed 6 new proteins differentially expressed in HBV-related HCC.

Conclusion

These findings elucidate that there are common features between CHB-developed HCC and LC-developed HCC. The identified proteins are valuable for studying the hepatocarcinogenesis, and may be potential diagnostic markers or therapeutic targets for HBV-related HCC.     

Comparison between the ICRU rectal point and modern volumetric parameters in brachytherapy for locally advanced cervical cancer

PurposeThe implementation of image-guided brachytherapy in cervical cancer raises the problem of adapting the experience acquired with 2D brachytherapy to this technique. The GEC-ESTRO (Groupe européen de curiethérapie – European Society for Radiotherapy and Oncology) has recommended reporting the dose delivered to the rectum in the maximally exposed 2 cm³ volume, but so far, the recommended dose constraints still rely on 2D data. The aim of this study was to evaluate the relationship between the doses evaluated at the ICRU rectal point and modern dosimetric parameters.Material and methodsFor each patient, dosimetric parameters were generated prospectively at the time of dosimetry and were reported. For analysis, they were converted in 2 Gy equivalent doses using an α/β ratio of 3 with a half-time of repair of 1.5 hours.ResultsThe dosimetric data from 229 consecutive patients treated for locally advanced cervical cancer was analyzed. The mean dose calculated at ICRU point (DICRU) was 55.75 Gy ± 4.15, while it was 59.27 Gy ± 6.16 in the maximally exposed 2 cm³ of the rectum (P = 0.0003). The D2 cm³ was higher than the DICRU in 78% of the cases. The mean difference between D2 cm³ and DICRU was 3.53 Gy ± 4.91. This difference represented 5.41% ± 7.40 of the total dose delivered to the rectum (EBRT and BT), and 15.49% ± 24.30 of the dose delivered when considering brachytherapy alone. The two parameters were significantly correlated (P = 0.000001), and related by the equation: D2 cm³ = 0.902 × DICRU + 0.984. The r² coefficient was 0.369.ConclusionIn this large cohort of patients, the DICRU significantly underestimates the D2 cm³. This difference probably results from the optimization process itself, which consists in increasing dwell times above the ICRU point in the cervix. Considering these findings, caution must be taken while implementing image-guided brachytherapy and dose escalation.     

宫颈癌VMAT与静态IMRT所致全身当量剂量比较

目的 比较VMAT和静态IMRT技术在宫颈癌放疗中所致患者全身当量剂量。方法选取2014年间收治的9例宫颈癌放疗患者, 针对每例患者设计出VMAT和IMRT计划。在进行VMAT和IMRT治疗中,使用热释光剂量计(TLDs)测量每例患者在剑突和眉间位置上的当量剂量Hp(10),并基于剑突位置上测量的当量剂量估算出患者全身当量剂量。配对t检验二者差异。结果采用VMAT技术在每例患者剑突和眉间位置上测量的当量剂量均低于IMRT技术。当给予患者50 Gy处方剂量,选取患者剑突位置的平均当量剂量作为代表患者全身当量剂量时,WMAT和IMRT放疗技术所致患者的全身当量剂量分别为364 mSv和538 mSv。结论 VMAT技术比IMRT技术可导致患者更低的全身当量剂量, 可降低辐射诱发癌症发生的危险度。     

A comparison of ICRU point doses and volumetric doses of organs at risk (OARs) in brachytherapy for cervical cancer

Introduction: In brachytherapy for cervix cancer, doses to organs at risk (OARs) are traditionally calculated using the ICRU‐38 point doses to rectum and bladder. Three‐dimensional image‐guided brachytherapy allows assessment of OAR dose with dose volume histograms (DVHs). The purpose of this study was to analyse the correlation between DVHs and ICRU point doses. Methods: Using the PLATO? planning system, the bladder, rectum and sigmoid were retrospectively contoured on 62 CT datasets for 20 patients treated with definitive radiotherapy. The median external beam radiotherapy dose was 45 Gy. Brachytherapy was delivered using a CT‐MRI compatible tandem and ovoids to a median dose of 24 Gy in three fractions. DVHs were calculated, and the minimum dose to 2 cc of tissue receiving the highest dose (D_2cc) was recorded and compared with the ICRU point doses (D_ICRU). Results: The mean rectal D_ICRU was 4.01 Gy compared with D_2cc of 4.28 Gy. The mean bladder D_ICRU was 6.74 Gy compared with D_2cc of 8.65 Gy. The mean sigmoid D_2cc was 4.58 Gy. The mean dose ratios (D_2cc/D_ICRU) were 1.08 for rectum and 1.39 for bladder. D_ICRU correlated with D_2cc for rectum (r = 0.76, P = 0.001) and for bladder (r = 0.78, P = 0.01). Conclusion: OAR doses assessed by DVH criteria were higher than ICRU point doses. The significant correlation between D_2cc and D_ICRU has allowed us to set DVH dose constraints for CT‐based brachytherapy and thus begin the transition from two‐dimensional to three‐dimensional image‐guided brachytherapy planning.     

A three-dimensional computed tomography-assisted Monte Carlo evaluation of ovoid shielding on the dose to the bladder and rectum in intracavitary radiotherapy for cervical cancer

PURPOSE: To determine the effects of Fletcher Suit Delclos ovoid shielding on dose to the bladder and rectum during intracavitary radiotherapy for cervical cancer. METHODS AND MATERIALS: The Monte Carlo method was used to calculate the dose in 12 patients receiving low-dose-rate intracavitary radiotherapy with both shielded and unshielded ovoids. Cumulative dose-difference surface histograms were computed for the bladder and rectum. Doses to the 2-cm(3) and 5-cm(3) volumes of highest dose were computed for the bladder and rectum with and without shielding. RESULTS: Shielding affected dose to the 2-cm(3) and 5-cm(3) volumes of highest dose for the rectum (10.1% and 11.1% differences, respectively). Shielding did not have a major impact on the dose to the 2-cm(3) and 5-cm(3) volumes of highest dose for the bladder. The average dose reduction to 5% of the surface area of the bladder was 53 cGy. Reductions as large as 150 cGy were observed to 5% of the surface area of the bladder. The average dose reduction to 5% of the surface area of the rectum was 195 cGy. Reductions as large as 405 cGy were observed to 5% of the surface area of the rectum. CONCLUSIONS: Our data suggest that the ovoid shields can greatly reduce the radiation dose delivered to the rectum. We did not find the same degree of effect on the dose to the bladder. To calculate the dose accurately, however, the ovoid shields must be included in the dose model.     

宫颈癌术后IG-VMAT剂量学及不良反应研究

目的 比较宫颈癌术后图像引导VMAT (IG-VMAT)与固定野IMRT (FF-IMRT)的剂量学差异和不良反应。方法 选取2013年间两家医院收治70例Ⅰ _b-Ⅱ _a期宫颈癌术后具有高危因素患者,均分为FF-IMRT与IGRT-VMAT组,比较两组患者靶区剂量和不良反应差异。结果 IG-VMAT组分次间x、y、z轴向摆位误差分别为(0.25±0.14)、(0.26±0.16)、(0.24±0.18) cm, 分次内的分别为(0.1±0.09)、(0.12±0.09)、(0.11±0.09) cm;x、y、z轴向外扩边界分别为0.75、0.84、0.78 cm。在相同处方剂量下IG-VMAT组适形度、治疗时间、机器跳数明显优于FF-IMRT (P=0.000)。IG-VMAT组膀胱、直肠和小肠D_mean、高剂量受照体积均低于FF-IMRT组(P=0.000)。IG-VMAT组急慢性胃肠道、泌尿系统及血液系统不良反应发生率明显降低(P<0.05)。结论 IG-VMAT不仅能在线实时调整摆位误差,且缩短治疗时间、降低OAR受量、减轻急慢性不良反应,适用于术后小肠位置下移者。     

宫颈癌IMRT中膀胱充盈一致性研究

目的 探讨膀胱容量仪在宫颈癌调强放疗过程中保持膀胱充盈一致性的作用。方法回顾性分析20例宫颈癌患者放疗期间膀胱体积变化确定膀胱容量仪的引入时机;选取10例正接受宫颈癌放疗患者,分析膀胱容量仪干预后测量的膀胱体积与CBCT图像勾画的膀胱体积的一致性,比较采用膀胱容量仪干预前后膀胱体积相对定位体积的变化。结果 20例患者100次CBCT图像相关样本的非参数检验显示不同分次膀胱体积相对定位时膀胱体积均不同(P<0.05)。10例患者Bland-Altman图显示膀胱容量仪测量的膀胱体积与CBCT图像勾画的体积有较好一致性,两种方法的平均差别为-6.66 cm³(95%CI为-53.15~39.83 cm³)。配对t检验显示干预前膀胱体积与定位时的体积不同(P=0.000),干预后膀胱体积与定位时的体积相近(P=0.745)。结论 患者分次治疗间膀胱体积变化较大,膀胱容量仪应在患者每次治疗前使用。使用膀胱容量仪测量膀胱体积以保证与计划设计时的一致性有重要意义。     

探讨食管癌外照射加腔内放疗与单纯外照射的疗效

目的比较食管癌外照射加腔内放射与单纯外照射治疗的生存率及副作用。材料与方法１９８９年２月～１９９２年７月１１０例经病理证实的食管中段癌，病变长度均小于７ｃｍ的放疗病例平均分成两组，Ａ组为单纯外照射组（对照组），Ｂ组为外照射加腔内放疗组（治疗组）。病例均无远处转移及锁骨上淋巴结转移。结果两组远期生存率无明显差别，近期副反应无明显差别，远期副反应及局部复发率Ａ组明显高于Ｂ组。结论两种治疗方法远期疗效无差别，外照射加腔内放疗，不仅减少局部复发率，还可减少全身反应，缩短治疗时间，不失为一种治疗食管癌的可行方法     

宫颈癌常规放疗联合腔内三维放疗的初步研究

目的 探讨体外放疗联合CT影像为基础近距离放疗的宫颈癌患者DVH参数和治疗结果间关系。方法 2008—2011年间18例接受根治性放疗的Ⅱ_B—Ⅲ_B期宫颈癌患者进行了常规放疗加CT为基础的近距离三维放疗。观察两种放疗相加的高危CTV的D₉₀和直肠、膀胱的D_{2 cm³} 、D_{1 cm³} ,采用EQD₂进行剂量叠加。同时随访患者不良反应。结果 A点剂量为(93.0±5.5) Gy,高危CTV D₉₀为(73.6±11.9) Gy。患者中位随访时间为26个月,无复发病例。8例患者出现轻中度直肠晚期反应,其直肠D_{2 cm³} 、D_{1 cm³} 均高于无反应者[(87.4±3.8) Gy∶(75.8±7.4) Gy,P=0.004;(96.4±6.6) Gy∶(80.5±7.1) Gy,P=0.001]。结论 CT引导的宫颈癌三维近距离放疗高危CTV D₉₀剂量比文献报道略低,直肠D_{2 cm³} 建议<75 Gy。     

Dose determination in bladder and rectum during intracavitary irradiation of cervix carcinoma

The radiation dosage in the base of the bladder and in the anterior wall of the rectum during intracavitary irradiation of cervix carcinoma can be determined easily by use of intracavitary transvesical and transrectal ultrasound and simultaneous radiography. In case of excessive doses to the organs at risk, the dose can be lowered by rearrangement of the vaginal gauze packing in the same sitting.     

膀胱体积变化对宫颈癌近距离放疗的影响

目的:分析膀胱体积变化对宫颈癌近距离治疗中肿瘤和正常组织受量的影响。方法:2015年1月至2017年12月于本院首诊的66例拟行根治性放疗的宫颈癌患者,治疗方案采用外照射放疗同期化疗加近距离治疗。均采用同期顺铂40 mg/m2每周方案化疗,外照射均采用常规分割外照射放疗,1.8~2 Gy/次,1次/天,5次/周,盆腔预防放疗剂量45 Gy/25次,阳性区域转移淋巴结处方剂量55~57.5 Gy/25次。后装采用三维自适应近距离放疗,A点剂量6 Gy每次,共4次,采用宫腔管和双侧阴道穹窿管或环形施源器,在定位CT图像上勾画高危临床靶区（high risk clinical tumor volume,HRCTV）、膀胱、直肠、乙状结肠,制定后装治疗计划后行近距离放疗。结果:后装近距离治疗期间,随着膀胱体积增大,膀胱D1cc、D2cc接受的放疗剂量逐渐升高,有显著统计学差异（P<0.001）,其中小于49.25 ml膀胱体积组膀胱受辐射量最小。而膀胱体积的变化不影响直肠D1cc和D2cc、乙状结肠D1cc和D2cc、HRCTV D90和HRCTV D95。随着后装次数的增加,膀胱体积有逐渐增加的趋势,虽然第一次后装时膀胱体积与第二、三次后装时膀胱体积无统计学差异,但是第一次后装时膀胱体积与第四次后装时膀胱体积有统计学差异(P=0.02)。结论:近距离治疗过程中控制膀胱体积可以减少膀胱受照射剂量,近距离治疗期间控制膀胱体积小于49.25 ml可能是一个更好地选择。     

宫颈癌术后容积旋转调强与三维适形调强放疗技术的剂量学差异

目的:比较宫颈癌术后放疗中旋转调强放射治疗(VMAT)与三维适形调强放疗(IMRT)的剂量学差异。方法:随机选取 20 例宫颈癌术后患者,在Eclipse计划系统中分别对每例患者进行容积旋转调强和7野固定野调强放疗(7IMRT)计划设计,比较两种技术的靶区的适形指数、危及器官的受照剂量、机器跳数和治疗时间的差异。结果:VMAT 技术靶区的平均剂量为52.05 Gy,高于 7IMRT技术的51.46 Gy(P＜0.05),靶区的均匀性指数与适形度优于7IMRT 技术,机器跳数和治疗时间 VMAT 比7IMRT明显减少,差异有统计学意义。小肠、膀胱的V30、V50 、Dmean较7IMRT降低,差异有统计学意义;但直肠和股骨头的保护性上,两种放疗技术差异无统计学意义。结论:VMAT技术较IMRT技术可得到更好的靶区剂量分布,危及器官也能得到更好的保护,治疗时间明显缩短,值得在临床中开展应用。     

Volume and hormonal effects for acute side effects of rectum and bladder during conformal radiotherapy for prostate cancer

PURPOSE: To identify dosimetric variables predictive of acute gastrointestinal (GI) and genitourinary (GU) toxicity and to determine whether hormonal therapy (HT) is independently associated with acute GI and GU toxicity in prostate cancer patients treated with conformal radiotherapy (RT). METHODS AND MATERIALS: This analysis was performed on 336 patients participating in a multicenter (four hospitals) randomized trial comparing 68 Gy and 78 Gy. The clinical target volume consisted of the prostate with or without the seminal vesicles, depending on the risk of seminal vesicle involvement. The margin from the clinical target volume to the planning target volume was 1 cm. For these patients, the treatment plan for a total dose of 68 Gy was used, because nearly all toxicity appeared before the onset of the 10-Gy boost. Acute toxicity (<120 days) was scored according to the Radiation Therapy Oncology Group criteria. The dosimetric parameters were obtained from the relative and absolute dose-volume/surface histograms derived from the rectal wall (rectal wall volume receiving > or =5-65 Gy) and the bladder surface (bladder surface receiving > or =5-65 Gy). Additionally, relative and absolute dose-length histograms of the rectum were created, and the lengths of rectum receiving more than a certain dose over the whole circumference (rectal length receiving > or =5-65 Gy) were computed. The clinical variables taken into account for GI toxicity were neoadjuvant HT, hospital, and dose-volume group; for GU toxicity, the variables pretreatment GU symptoms, neoadjuvant HT, and transurethral resection of the prostate were analyzed. The variable neoadjuvant HT was divided into three categories: no HT, short-term neoadjuvant HT (started < or =3 months before RT), and long-term neoadjuvant HT (started >3 months before RT). RESULTS: Acute GI toxicity Grade 2 or worse was seen in 46% of the patients. Patients with long-term neoadjuvant HT experienced less Grade 2 or worse toxicity (27%) compared with those receiving short-term neoadjuvant HT (50%) and no HT (50%). The volumes of the prostate and seminal vesicles were significantly smaller in both groups receiving neoadjuvant HT compared with those receiving no HT. In multivariate logistic regression analysis, including the two statistically significant clinical variables neoadjuvant HT and hospital, a volume effect was found for the relative, as well as absolute, rectal wall volumes exposed to intermediate and high doses. Of all the length parameters, the relative rectal length irradiated to doses of > or =5 Gy and > or =30 Gy and absolute lengths receiving > or =5-15 and 30 Gy were significant. Acute GU toxicity Grade 2 or worse was reported in 56% of cases. For patients with pretreatment GU symptoms, the rate was 93%. The use of short-term and long-term neoadjuvant HT resulted in more GU toxicity (73% and 71%) compared with no HT (50%). In multivariate analysis, containing the variables pretreatment symptoms and neoadjuvant HT, only the absolute dose-surface histogram parameters (absolute surface irradiated to > or =40, 45, and 65 Gy) were significantly associated with acute GU toxicity. CONCLUSION: A volume effect was found for acute GI toxicity for relative, as well as absolute, volumes. With regard to acute GU toxicity, an area effect was found, but only for absolute dose-surface histogram parameters. Neoadjuvant HT appeared to be an independent prognostic factor for acute toxicity, resulting in less acute GI toxicity, but more acute GU toxicity. The presence of pretreatment GU symptoms was the most important prognostic factor for GU symptoms during RT.     

腔内微波热疗联合放疗治疗中晚期宫颈癌临床观察

目的 观察腔内微波热疗加放疗治疗宫颈癌的临床疗效.方法 66例宫颈癌患者随机分为热疗加放疗组(热放组)33例,单纯放疗组(单放组)33例.两组放射治疗方法相同,均采用8 Mv-X线全盆腔外照射DT 30 Gy,盆腔4野DT 20 Gy,加192Ir高剂量率腔内后装治疗,A点DT 42 Gy.热疗采用915 MHz微波热疗仪,放疗后30 rain-1 h内进行,腔内加温43-45℃,每次45 min,每周1-2次,共7-10次.结果 热放组与单放组局部控制率、感染率分别为87.88%和63.63%、15.15%和36.36%,差异均有统计学意义(P<0.05),热放组治疗后CD4/CD8比值及自然杀伤细胞数较治疗前升高(P<0.05),与单放组比较差异有统计学意义(P<0.05).2年肿瘤无进展生存率及3年生存率热放组与单放组分别为93.94%和72.72%、84.85%和60.61%,差异均有统计学意义(P<0.05).骨髓抑制及放射性直肠炎发生率热放组均低于单放组.结论 腔内微波热疗联合放疗能提高宫颈癌的局部控制率及生存率.     

ICRU 83号报告推荐方式评估宫颈癌术后辅助IMRT与传统放疗方式的差异及可行性

目的：以国际辐射单位与测量委员会（International Commission on Radiation Units and Measurements, ICRU）83号报告推荐的方式评估调强适形放疗（intensity-modulated radiotherapy,IMRT）方式与传统二维二野等中心放疗方式用于宫颈癌术后辅助放疗的差异及可行性。方法回顾性分析10例宫颈癌术后IMRT和模拟传统二维放疗的剂量体积直方图（dose-volume histogram,DVH）数据。统计计划靶区体积（planning target volume,PTV）、D100、D98、D95、D50、Dmean、D2、D0,计算均匀性指数（homogeneity index,HI）;以D50评估不同放疗方式对剂量的影响;分别统计危及器官（organs at risk,OAR）的DVH参数并进行分析。结果以D50评估IMRT方式的PTV剂量较二维放疗方式提高4.47%±3.62%,其实际差值为（200±157）cGy（t=4.2,P=0.001）。IMRT中骨盆的V10和V20高于二维放疗,V30的差异无统计学意义。IMRT中小肠的V10和V20高于二维放疗,V40低于二维放疗。IMRT中膀胱和直肠的V40、Dmean低于二维放疗,而以D1c、D2c、D2和Dmax为指标评估高剂量区,两种放疗方式的差异无统计学意义。结论 ICRU 83号报告推荐方式适用于IMRT计划评估;IMRT较传统放疗方式提高了靶区剂量,增加了骨盆和小肠的低剂量受照体积,降低了膀胱和直肠的整体受照剂量,但仍存在小体积较高剂量。若采用D50作为评估标准,可考虑降低剂量4.47%±3.62%。