宫颈癌后装治疗常规计划与逆向计划剂量学对比

目的对比分析宫颈癌常规计划和逆向计划（即模拟退火逆向优化计划）的剂量学差异。方法选取宫颈癌内外照射联合根治性放疗的患者20例,每例患者制定两个治疗计划：一个为基于A点给定处方剂量的常规计划;另一个为逆向计划,先满足靶区,优化时,当临床靶区(CTV)的90％处方剂量体积大于90％ CTV时即达到优化目标,否则调节目标函数的权重配比,重新优化,直到达到优化目标。结果逆向计划的90％处方剂量体积和100％处方剂量体积及100％目标体积受量[(94±15)％、(90±18)％、(54±10)％]均优于常规计划[(60±17)％、(56±14)％、(29±9)％](P＜0.05),同时危及器官亦得到较好的保护。结论逆向优化的治疗计划具有节省时间,提高靶区剂量,减少危及器官受量的优势。     

Caudal epidural anesthesia during intracavitary brachytherapy for cervical cancer

It has been suggested that pain control during intracavitary brachytherapy for cervical cancer is insufficient in most hospitals in Japan. Our hospital began using caudal epidural anesthesia during high-dose-rate (HDR) intracavitary brachytherapy in 2011. The purpose of the present study was to retrospectively investigate the effects of caudal epidural anesthesia during HDR intracavitary brachytherapy for cervical cancer patients. Caudal epidural anesthesia for 34 cervical cancer patients was performed during HDR intracavitary brachytherapy between October 2011 and August 2013. We used the patients'' self-reported Numeric Rating Scale (NRS) score at the first session of HDR intracavitary brachytherapy as a subjective evaluation of pain. We compared NRS scores of the patients with anesthesia with those of 30 patients who underwent HDR intracavitary brachytherapy without sacral epidural anesthesia at our hospital between May 2010 and August 2011. Caudal epidural anesthesia succeeded in 33 patients (97%), and the NRS score was recorded in 30 patients. The mean NRS score of the anesthesia group was 5.17 ± 2.97, significantly lower than that of the control group''s 6.80 ± 2.59 (P = 0.035). The caudal epidural block resulted in no side-effects. Caudal epidural anesthesia is an effective and safe anesthesia option during HDR intracavitary brachytherapy for cervical cancer.     

宫颈癌三维后装近距离治疗技术研究进展

宫颈癌是常见的女性生殖系统恶性肿瘤,在发展中国家及落后地区发病率较高。放射治疗是宫颈癌治疗的主要手段之一,其中近距离治疗是宫颈癌放疗中必不可少的重要组成部分。随着CT以及MRI等影像技术的迅猛发展,宫颈癌近距离治疗已从传统的二维影像引导技术逐渐发展成为三维影像引导技术,且治疗方式也越来越多,包括腔内近距离治疗、组织间插植近距离治疗以及腔内联合组织间插植近距离治疗等。本文对宫颈癌三维后装近距离治疗的几种常见技术进行综述,同时讨论内外融合照射方式的剂量学可行性。     

Inverse planning for combination of intracavitary and interstitial brachytherapy for locally advanced cervical cancer

The main purpose of this study was to compare three different treatment plans for locally advanced cervical cancer: (i) the inverse-planning simulated annealing (IPSA) plan for combination brachytherapy (BT) of interstitial and intracavitary brachytherapy, (ii) manual optimization based on the Manchester system for combination-BT, and (iii) the conventional Manchester system using only tandem and ovoids. This was a retrospective study of 25 consecutive implants. The high-risk clinical target volume (HR-CTV) and organs at risk were defined according to the GEC-ESTRO Working Group definitions. A dose of 6 Gy was prescribed. The uniform cost function for dose constraints was applied to all IPSA-generated plans. The coverage of the HR-CTV by IPSA for combination-BT was equivalent to that of manual optimization, and was better than that of the Manchester system using only tandem and ovoids. The mean V₁₀₀ achieved by IPSA for combination-BT, manual optimization and Manchester was 96 ± 3.7%, 95 ± 5.5% and 80 ± 13.4%, respectively. The mean D₁₀₀ was 483 ± 80, 487 ± 97 and 335 ± 119 cGy, respectively. The mean D₉₀ was 677 ± 61, 681 ± 88 and 513 ± 150 cGy, respectively. IPSA resulted in significant reductions of the doses to the rectum (IPSA D_2cm³: 408 ± 71 cGy vs manual optimization D_2cm³: 485 ± 105 cGy; P = 0.03) and the bladder (IPSA D_2cm³: 452 ± 60 cGy vs manual optimization D_2cm³: 583 ± 113 cGy; P < 0.0001). In conclusion, combination-BT achieved better tumor coverage, and plans using IPSA provided significant sparing of normal tissues without compromising CTV coverage.     

Different effects of bladder distention on point A-based and 3D-conformal intracavitary brachytherapy planning for cervical cancer

This study sought to evaluate the differential effects of bladder distention on point A-based (AICBT) and three-dimensional conformal intracavitary brachytherapy (3D-ICBT) planning for cervical cancer. Two sets of CT scans were obtained for ten patients to evaluate the effect of bladder distention. After the first CT scan, with an empty bladder, a second set of CT scans was obtained with the bladder filled. The clinical target volume (CTV), bladder, rectum, and small bowel were delineated on each image set. The AICBT and 3D-ICBT plans were generated, and we compared the different planning techniques with respect to the dose characteristics of CTV and organs at risk. As a result of bladder distention, the mean dose (D₅₀) was decreased significantly and geometrical variations were observed in the bladder and small bowel, with acceptable minor changes in the CTV and rectum. The average D_{2 cm³}and D_{1 cm³}showed a significant change in the bladder and small bowel with AICBT; however, no change was detected with the 3D-ICBT planning. No significant dose change in the CTV or rectum was observed with either the AICBT or the 3D-ICBT plan. The effect of bladder distention on dosimetrical change in 3D-ICBT planning appears to be minimal, in comparison with AICBT planning.     

宫颈癌高剂量率近距离计划中的标准载源模型进展

近距离放射治疗在宫颈癌的根治性放射治疗中有着重要的地位.目前,国内绝大部分医院采用高剂量率近距离治疗方式,通过单一近似点源模拟线源来实现体积照射.因此,驻留位置和驻留时间可以进行适当的优化.然而,由于种种原因优化计划的初始状态必须从标准载源模型开始,并且保证优化后的计划基本保持梨形剂量分布.本文通过文献综述介绍了宫颈癌...     

Interfractional change of high-risk CTV D90 during image-guided brachytherapy for uterine cervical cancer

The purpose of this study was to evaluate interfractional changes of the minimum dose delivered to 90% of the high-risk clinical target volume (HR-CTV D90) and D2cc of the bladder and rectum during brachytherapy for uterine cervical cancer patients. A total of 52 patients received external beam radiotherapy and high-dose-rate intracavitary brachytherapy (ICBT). For each of four ICBT applications, a pelvic CT scan was performed and the HR-CTV was delineated. Retrospectively, these patients were divided into two groups: (i) the standard dose group with 6 Gy to point A in each ICBT, and (ii) the adaptive dose group with a modified dose to point A to cover the HR-CTV with the 6-Gy isodose line as much as possible. The HR-CTV D90 was assessed in every session, and analyzed as interfractional changes. In the standard dose group, the interfractional changes of the HR-CTV D90 showed a linear increase from the first to the third of the four ICBT (average 6.1, 6.6, 7.0 and 7.1 Gy, respectively). In contrast, those of the adaptive dose group remained almost constant (average 7.2, 7.2, 7.3 and 7.4 Gy, respectively). Especially, in the case of a large HR-CTV volume (≥35 cm³) at first ICBT, the total HR-CTV D90 of the adaptive dose group with brachytherapy was significantly higher than that of the standard dose group. There were no significant differences in total D2cc in bladder and rectum between the two groups. Image-guided adaptive brachytherapy based on interfractional tumor volume change improves the dose to the HR-CTV while keeping rectal and bladder doses within acceptable levels.     

Preliminary results of magnetic resonance imaging-aided high-dose-rate interstitial brachytherapy for recurrent uterine carcinoma after curative surgery

This report presents initial experience with imaging-aided high-dose-rate interstitial brachytherapy (HDR-ISBT) for post-operative recurrence of uterine carcinoma. Fourteen patients presenting with post-operative recurrence of uterine carcinoma (nine cervix and five corpus) between July 2005 and October 2008 were enrolled in this study (median follow-up: 37 months, range: 6-59 months). We implanted magnetic resonance imaging (MRI)-compatible plastic applicators using our own ambulatory technique. HDR-ISBT treatment consisted of twice-a-day irradiation of 6 Gy each with at least a six-hour interval to provide the total prescribed dose. Treatment was based on treatment planning-computed tomography with MRI as a reference. Seven patients were treated with a combination of ISBT (median 30 Gy/5 fractions; range: 27-33 Gy) and external beam radiation therapy (EBRT), and the other seven with brachytherapy only (median 54 Gy/9 fractions; range: 48-54 Gy), one of whom had previously received pelvic EBRT. The three-year estimates of local control and overall survival rates were 77.9% (95% confidence interval (CI): 55.8-100%) and 77.1% (95% CI: 54.2-100%), respectively. Two patients, who had received combined treatment with EBRT showed untoward reactions, including a grade 3 subileus and grade 2 constipation. Another patient, who had been treated with ISBT alone, developed grade 2 urinary constriction. Our imaging-aided HDR-ISBT for post-operative recurrence of uterine carcinoma was found to be practical with promising preliminary results.     

Small dose of oral gastrografin for computed tomography-based image-guided brachytherapy in patients with uterine cervical cancer

Oral administration of a water-soluble iodine contrast agent (gastrografin) was reported to assist in the appropriate contouring of the small intestine on computed tomography (CT)-based radiotherapy (RT) planning. The efficacy and optimal dose of gastrografin in CT-based image-guided brachytherapy (IGBT) for cervical cancer remain unknown. This study aimed to investigate the efficacy of pretreatment oral administration of gastrografin at a small dose of 50 ml in CT-based IGBT for cervical cancer. A total of 422 sessions in 137 patients who underwent CT-based IGBT with 50 ml of oral gastrografin (concentration, 3% or 4%) were analyzed. Preparation of gastrografin was judged as effective when the small intestine was contrast-enhanced at the area where the small intestine was in contact with the uterus/adnexa. About 287 out of 422 sessions (68%) were judged as effective with gastrografin preparation. The 135 ineffective sessions were considered as follows: (i) the contrast enhancement of the small intestine was not confirmed (n = 36), (ii) the small intestine was not in contact with the uterus/adnexa despite the confirmation of the contrast enhancement of the small intestine (n = 34), and (iii) gastrografin was absent in the small intestine at the area in contact with the uterus/adnexa, even when gastrografin was observed in the small intestine at the area not in contact with the uterus/adnexa (n = 65). In conclusion, pretreatment oral administration of a small dose gastrografin achieved moderate efficacy for accurate contouring of the small intestine close to the uterus/adnexa in CT-based IGBT for cervical cancer.     

宫颈癌患者近距离放疗局部感染的临床分析

目的探讨宫颈癌患者近距离放疗后局部感染情况,分析阴道分泌物的病原菌分布及耐药性,为临床防治局部感染提供依据。方法选取2013年1月-2014年12月医院就诊并实施近距离放疗的356例宫颈癌患者为研究对象,调查分析患者放疗后局部感染情况、阴道分泌物病原菌分布及其耐药性。结果 356例患者中68例发生局部感染,感染率为19.1%;共分离病原菌75株,其中革兰阴性菌50株占66.7%,以大肠埃希菌和奇异变形菌为主,革兰阳性菌22株占29.3%,以葡萄球菌属和肠球菌属为主,真菌3株占4.0%,以白色假丝酵母菌为主,大肠埃希菌对头孢噻肟、头孢吡肟、头孢他啶、阿莫西林、哌拉西林、环丙沙星和庆大霉素耐药率较高,耐药率为62.5%~93.8%;奇异变形菌对阿莫西林和庆大霉素耐药率较高,耐药率为66.7%和55.6%;葡萄球菌属对青霉素G、红霉素、环丙沙星、左氧氟沙星和氨苄西林高度耐药,耐药率为53.8%~92.3%;肠球菌属对庆大霉素、红霉素和左氧氟沙星高度耐药,耐药率为66.7%~100.0%。结论宫颈癌近距离放疗合并局部感染率较高,临床应加强感染病原菌检测,掌握病原菌种类及其耐药性,指导临床合理使用抗菌药物,提高患者临床治疗效果。     

Estimation of the total rectal dose of radical external beam and intracavitary radiotherapy for uterine cervical cancer using the deformable image registration method

We adapted the deformable image registration (DIR) technique to accurately calculate the cumulative intracavitary brachytherapy (ICBT) and external beam radiotherapy (EBRT) rectal dose for treating uterine cervical cancer. A total of 14 patients with primary cervical cancer radically treated with ICRT and EBRT were analysed using the Velocity AI^TM software. Computed tomography (CT) images were registered, and EBRT and ICBT dose distributions were determined. Cumulative D_2cm³, D_1cm³ and D_0.1cm³ were calculated by simple addition of fractional values or by DIR. The accuracy of DIR was evaluated by means of a virtual phantom mimicking the rectum. The dice similarity coefficient (DSC) was calculated to evaluate rectal contour concordance between CT images before and after DIR. Virtual phantom analysis revealed that the average difference between the DIR-based phantom D_mean and the simple phantom D_mean was 1.9 ± 2.5 Gy (EQD₂), and the DIR method included an uncertainty of ∼8.0%. The mean DSC between reference CT and CT was significantly improved after DIR (EBRT: 0.43 vs 0.85, P < 0.005; ICBT: 0.60 vs 0.87, P < 0.005). The average simple rectal D_2cm³, D_1cm³ and D_0.1cm³ values were 77.6, 81.6 and 91.1 Gy (EQD₂), respectively; the DIR-based values were 76.2, 79.5 and 87.6 Gy, respectively. The simple addition values were overestimated, on average, by 3.1, 3.7 and 5.5 Gy, respectively, relative to the DIR-based values. In conclusion, the difference between the simple rectal dose–volume histogram (DVH) parameter addition and DIR-based cumulative rectal doses increased with decreasing DVH parameters.     

Intracavitary combined with CT-guided interstitial brachytherapy for locally advanced uterine cervical cancer: introduction of the technique and a case presentation

We report a new technique of brachytherapy consisting of intracavitary combined with computed tomography (CT)-guided interstitial brachytherapy for locally advanced cervical cancer. A Fletcher-Suit applicator and trocar point needles were used for performing high-dose rate brachytherapy under in-room CT guidance. First, a tandem and ovoids were implanted into the patient's vagina and uterus by conventional brachytherapy method. Based on clinical examination and MRI/CT imaging, operating radiation oncologists decided the positions of insertion in the tumor and the depth of the needles from the upper surface of the ovoid. Insertion of the needle applicator was performed from the vaginal vault inside the ovoid within the tumor under CT guidance. In treatment planning, dwell positions and time adaptations within the tandem and ovoids were performed first for optimization based on the Manchester system, and then stepwise addition of dwell positions within the needle was continued. Finally, dwell positions and dwell weights were manually modified until dose-volume constraints were optimally matched. In our pilot case, the dose of D90 to high-risk clinical target volume was improved from 3.5 Gy to 6.1 Gy by using our hybrid method on the dose-volume histogram. D1cc of the rectum, bladder and sigmoid colon by our hybrid method was 4.8 Gy, 6.4 Gy and 3.5 Gy, respectively. This method consists of advanced image-guided brachytherapy that can be performed safely and accurately. This approach has the potential of increasing target coverage, treated volume, and total dose without increasing the dose to organs at risk.     

宫颈癌患者磁共振成像特征及扩散加权成像参数与临床病理特征的关系

目的研究宫颈癌患者磁共振成像特征及扩散加权成像(DWI)参数与临床病理特征的关系。方法回顾性分析2013年3月-2017年6月该院收治的100例宫颈癌患者的临床资料,所有患者均给予常规磁共振平扫以及DWI检查,并分析宫颈癌患者临床病理特征与磁共振成像特征及DWI参数的相关性。结果病变部位以宫颈为中心,信号特征为T_1WI呈等信号,T_2WI呈高信号,T_2脂肪抑制序列(T_2FS)呈显著高信号,DWI呈高信号。宫颈癌分化程度为中或高、无淋巴结转移以及肿瘤细胞间质占比70%患者的表观弥散系数(ADC)值分别高于分化程度为低分化、有淋巴结转移以及肿瘤细胞间质占比≥70%患者,差异均有统计学意义(均P0.05),宫颈癌病理分期为Ⅰ~Ⅱ期和Ⅲ~Ⅳ期ADC值差异无统计学意义(P0.05)。经Spearman相关性分析可得:宫颈癌患者临床病理分期与ADC值无关,肿瘤分化程度与ADC值呈正相关(r=0.523,P=0.000),淋巴结转移以及肿瘤细胞间质占比与ADC值均呈负相关(r=-0.565,P=0.000;r=-0.572,P=0.000)。结论磁共振成像特征以及DWI参数均与宫颈癌患者的临床病理特征密切相关,可为临床上宫颈癌治疗、预后评估提供指导作用。     

Preliminary results of conformal computed tomography (CT)-based intracavitary brachytherapy (ICBT) for locally advanced cervical cancer: a single institution's experience

Intracavitary brachytherapy using tandem and ovoids is an important component of definitive treatment for cervical cancer. In the present study, we analyzed the dose-volume histograms (DVHs) of the tumor volume and organs at risk including the sigmoid colon by CT-based treatment planning for high dose rate (HDR) intracavitary brachytherapy (ICBT) in cervical cancer. Seventeen patients with carcinoma of the cervix uteri were treated with external beam radiotherapy plus concurrent chemotherapy. For brachytherapy, the planning procedure started by performing a conventional plan which prescribed a dose of 6.5-7 Gy per fraction to point A, then optimized the dose based on CT imaging. Volumes and DVHs were calculated for the HR-CTV, bladder, rectum and sigmoid colon. The mean BED(2Gy) total doses of post-optimized plans of HR-CTV, bladder, rectum and sigmoid colon were: 89.6, 94.1, 74.0 and 69.8 Gy, respectively. For conventional plans, the calculated mean BED(2Gy) total doses of HR-CTV, bladder, rectum and sigmoid colon were 92.2, 120.1, 75.7 and 78.3 Gy, respectively. This study showed statistical significant higher BED(2Gy) total doses for bladder and sigmoid colon (p < 0.001) using conventional plans versus post-optimized, CT-based plans, while no difference between HR-CTV and rectum BED(2Gy) total doses could be detected. After a median follow-up of nineteen months, all seventeen patients had a clinical complete response. Two patients developed distant metastasis. Compared with conventional treatment, CT based brachytherapy planning was very effective in reducing doses to OARs, especially bladder and sigmoid colon whilst maintaining a high therapeutic dose for tumor target volumes in the treatment of cervical carcinoma.     

Clinical results of external beam radiotherapy alone with a concomitant boost program or with conventional fractionation for cervical cancer patients who did not receive intracavitary brachytherapy

A combination of external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) is well established as the standard radical radiotherapy (RT) for cervical cancer. However, it is sometimes necessary to perform EBRT alone for patients where ICBT is not feasible. For these patients, we initiated EBRT alone with three-dimensional conformal radiotherapy (3DCRT). The purpose of this study is to evaluate the results of EBRT alone without ICBT for patients with cervical cancer. Sixteen patients were treated with EBRT alone between 2002 and 2009. There were three stage IIB, six stage IIIB and seven patients with stage IVA disease. A total of 10 patients were treated with a median dose of 66 Gy with a median overall treatment time (OTT) of 40 days delivered by a concomitant boost (CCB), and a median dose of 60 Gy with a median OTT of 47 days was administered for six patients by conventional fractionation (CF). The 3-year overall survival (OAS) and local control (LC) rates were 43.8% and 75.0%, respectively. The 3-year LC rate was 90.0% for the CCB group, 50.0% for the CF group (P = 0.0692); 100% for OTT ≤42 days, 42.9% for OTT ≥43 days (P = 0.0095). No severe acute and late adverse effects were encountered for any of the patients. These outcomes suggest that EBRT with a CCB program may be a promising radical treatment for cervical cancer that provides better LC with minimal complications, especially in cases where ICBT cannot be performed.     

Global expression analysis in uterine cervical cancer: metabolic pathways and altered genes

High risk human papillomavirus (HPV) infection is considered to be the most important etiological factor of Cervical Uterine Cancer. In order to determine the global expression pattern and to identify possible molecular markers of cervical cancer, cDNA arrays with probe sets complementary to 8,000 human genes were used to examine the expression profiles among 5 cell lines derived from human cervical cancer, three HPV16(+) tumor samples and three normal cervical tissues HPV(-). The levels of expression of different cellular processes were identified. Hierarchical clustering was performed and the gene expression using RT-PCR was confirmed. Two genes were found to be consistently overexpressed in invasive cervical cancer biopsies; one of them, IL-6 was previously reported to be overexpressed in cervical cancer and one novel gene, MMP10, previously not known to be related to cervical cancer. Hierarchical clustering of the expression data revealed that samples with common HPV type infection grouped together, maybe this could mean that differences between HPV types could be indirectly determined by expression profiles.     

Pelvic insufficiency fracture after definitive radiotherapy for uterine cervical cancer: retrospective analysis of risk factors

The purpose of this study is to determine the incidence, clinical characteristics and risk factors of postradiation pelvic insufficiency fracture (PIF) in women with uterine cervical cancer. We reviewed the medical records of 126 patients who received definitive radiotherapy (RT) for uterine cervical cancer between 2003 and 2009 at our institution. Among them, 99 patients who underwent at least one computed tomography (CT) or magnetic resonance imaging of the pelvis during their follow-up at more than 6 months were included in this analysis. The relationship between the incidence of PIF and several patient- and treatment-related factors was analyzed. The median follow-up period was 21 months. Of the 126 patients, 33 (with a total of 50 lesions) were diagnosed with PIF. The 2-year cumulative incidence was 32%. Univariate analysis showed that age ≥70 years (P= 0.0010), postmenopausal state (P = 0.0013), and lower CT density of bone and bone marrow (P= 0.020) significantly related to PIF. In a multivariate analysis, of the 59 patients whose CT densities were evaluable, lower CT density was the only significant factor associated with PIF (P = 0.0026). In conclusion, postradiation PIFs were detected in a considerable number of patients after definitive RT for cervical cancer. Predisposing factors were older age, postmenopausal state, and decreased density of bone and bone marrow on CT.