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.     

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.     

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.     

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.     

A questionnaire-based survey on 3D image-guided brachytherapy for cervical cancer in Japan: advances and obstacles

The purpose of this study is to survey the current patterns of practice, and barriers to implementation, of 3D image-guided brachytherapy (3D-IGBT) for cervical cancer in Japan. A 30-item questionnaire was sent to 171 Japanese facilities where high-dose-rate brachytherapy devices were available in 2012. In total, 135 responses were returned for analysis. Fifty-one facilities had acquired some sort of 3D imaging modality with applicator insertion, and computed tomography (CT) and magnetic resonance imaging (MRI) were used in 51 and 3 of the facilities, respectively. For actual treatment planning, X-ray films, CT and MRI were used in 113, 20 and 2 facilities, respectively. Among 43 facilities where X-ray films and CT or MRI were acquired with an applicator, 29 still used X-ray films for actual treatment planning, mainly because of limited time and/or staffing. In a follow-up survey 2.5 years later, respondents included 38 facilities that originally used X-ray films alone but had indicated plans to adopt 3D-IGBT. Of these, 21 had indeed adopted CT imaging with applicator insertion. In conclusion, 3D-IGBT (mainly CT) was implemented in 22 facilities (16%) and will be installed in 72 (53%) facilities in the future. Limited time and staffing were major impediments.     

Survival outcome of cervical cancer patients treated by image-guided brachytherapy: a ‘real world’ single center experience in Thailand from 2008 to 2018

The objective of our study was to evaluate the survival outcome of cervical cancer patients treated using image-guided brachytherapy (IGBT). From 2008 to 2018, 341 patients with cervical cancer were treated by radical radiotherapy. IGBT (by computed tomography [CT] or transabdominal ultrasound [TAUS]) was used to treat all of these patients. The characteristic data and patient status after treatment were recorded. All data were evaluated for survival outcome analysis. From a total of 341 patients, 295 patients were analyzed and 46 patients were excluded due to data missing in the survival outcomes. At the median follow-up time of 48 months (IQR 30–80 months), The 4-year local control, progression-free survival and overall survival rates were 89.5%, 74.9% and 69.1%, respectively. For overall survival, the size (> 5 cm), pathology (non-SCCA), stage (stage III–IV by FIGO 2009), lymph node (LN) (presented) and overall treatment time (OTT) (> 56 days) showed statistical significance in univariate analysis while non-SCCA pathology, advanced stage, presented LN and longer OTT showed statistical significance in multivariate analysis. In conclusion, our analysis reports a 4-year overall survival rate of 69.1%. Non-SCCA pathology, advanced stage disease, LN presence and longer OTT showed worse prognostic factors in multivariate analysis.     

Dosimetric and geometric evaluation of the use of deformable image registration in adaptive intensity-modulated radiotherapy for head-and-neck cancer

The aim of this study was to carry out geometric and dosimetric evaluation of the usefulness of a deformable image registration algorithm utilized for adaptive head-and-neck intensity-modulated radiotherapy. Data consisted of seven patients, each with a planning CT (pCT), a rescanning CT (ReCT) and a cone beam CT (CBCT). The CBCT was acquired on the same day (±1 d) as the ReCT (i.e. at Fraction 17, 18, 23, 24 or 29). The ReCT served as ground truth. A deformed CT (dCT) with structures was created by deforming the pCT to the CBCT. The geometrical comparison was based on the volumes of the deformed, and the manually delineated structures on the ReCT. Likewise, the center of mass shift (CMS) and the Dice similarity coefficient were determined. The dosimetric comparison was performed by recalculating the initial treatment plan on the dCT and the ReCT. Dose–volume histogram (DVH) points and a range of conformity measures were used for the evaluation. We found a significant difference in the median volume of the dCT relative to that of the ReCT. Median CMS values were ∼2–5 mm, except for the spinal cord, where the median CMS was 8 mm. Dosimetric evaluation of target structures revealed small differences, while larger differences were observed for organs at risk. The deformed structures cannot fully replace manually delineated structures. Based on both geometrical and dosimetrical measures, there is a tendency for the dCT to overestimate the need for replanning, compared with the ReCT.     

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.     

Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer

In patients undergoing radiotherapy for localized prostate cancer, dose–volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose–volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9–53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0–1 and Grades 2–3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session.     

Comparison of a community outreach service with opportunity screening for cervical cancer using Pap smears

We sought to compare the take-up of cervical screening with Pap smears in a new outreach and pre-existing hospital-based setting (1) to assess the extent to which the two means of provision would overlap; (2) to establish how the utilization rate is influenced by demographic features and geographical distance from the point of provision; and (3) to access whether an outreach service would lead to increased utilization. We used a pre-test-post-test design and used multiple linear regression to assess the effect an outreach service has on utilization after adjusting for participants age, education and martial status. We found that the outreach service independently provided screening to 89% of eligible women and that coverage was inversely associated with distance from the pre-existing hospital provision. After controlling for age, education and martial status, there was a statistically significant increase (53%; 95% CI: 25, 80%) in utilization. There was little overlap between the outreach and hospital-based cervical screening services so that overall accessibility was enhanced, particularly for the elderly, widowed and less well educated. The outreach service also reduced inequalities due to geography.     

血管内皮生长因子C在宫颈癌及宫颈癌前病变患者血清的表达水平及临床意义

目的探讨血管内皮生长因子C（VEGF-C）在宫颈癌、宫颈癌前病变患者血清的表达水平及临床意义。方法收集并回顾性分析2010年4月-2013年4月于武汉市江夏区第一人民医院门诊疑诊为宫颈癌的74例患者的临床资料,其中手术后病检结果为宫颈上皮内瘤变Ⅱ／Ⅲ级38例,宫颈癌不伴淋巴结转移18例。宫颈癌伴淋巴结转移18例,分别归为A、B、C组;同时选取74例同期子宫肌瘤患者为正常对照,归为对照组。采用酶联免疫吸附试验法检测148例研究对象血清中VEGF-C表达水平,并比较三组间的差异,采用ROC曲线探讨VEGF-C对宫颈癌淋巴结转移的预测价值。结果C组的VEGF-C水平显著高于其他三组（P〈0．05）,B组VEGF-C水平较A组和对照组高（P〈0．05）,A组的VEGF-C水平显著高于对照组（P〈0．05）。宫颈鳞癌FIGOIU期患者的血清VEGF-C水平显著高于Ⅰ期和Ⅱ期患者（P〈0．05）,但不同分化程度其血清VEGF-C水平无显著差异（P〉0．05）。ROC曲线分析结果显示,当将VEGF-c诊断阈值设定为353．0ng／L时,预测宫颈癌淋巴结转移的敏感度为84．0％,特异性为83．5％,VEGF-C曲线下面积为97．4％。结论对宫颈癌患者进行血清VEGF-C水平测定可初步预测宫颈癌预后,具有重要临床意义。     

年轻宫颈癌的临床特征与预后分析

目的:探讨年轻宫颈癌的临床特征与预后分析。方法:2001年1月～2006年12月该院共收治宫颈癌患者587例,术后均经病理证实为宫颈癌,年龄22～65岁。以其中≤35岁者67例作为研究组,并随机抽取同期35岁的宫颈癌患者125例作为对照组,比较分析两组患者临床资料、病理分期、宫颈形态、病理分型、组织学分级、临床表现以及预后生存率等方面的差异。结果:与对照组相比,观察组初次性交20岁、避孕药使用史、原位癌及Ⅰ期的比率明显增高,HPV感染史及Ⅱ期比率明显降低,差异均具有统计学意义(P0.05),而两组宫颈形态、病理分型及组织学分级等方面无明显差异(P0.05)。与此同时,观察组接触性阴道出血的比率明显提高,阴道不规则出血及白带增多的比率明显降低,差异具有统计学意义(P0.05)。结论:加强对年轻人宫颈癌防治知识的宣传的力度,采取积极合理的宫颈癌筛查方法,早诊断、早治疗对年轻宫颈癌的防治具有重要的临床意义。     

Dose rate in the highest irradiation area of the rectum correlates with late rectal complications in patients treated with high-dose-rate computed tomography-based image-guided brachytherapy for cervical cancer

The purpose of this study was to evaluate the effect of dose rate to the rectum on late rectal complications in patients treated with computed tomography (CT)-based image-guided brachytherapy (IGBT) for cervical cancer. The subjects were 142 patients with cervical cancer who underwent Ir-192 high-dose-rate (HDR)-IGBT between March 2012 and January 2018. The dose rate to the rectum was calculated using in-house software. The minimum, mean and maximum effective dose rate (EDR) was calculated for voxels of the rectal volume covered by cumulative doses >D_0.1cc, >D_2cc, and > D_5cc. The average EDR of three to four brachytherapy sessions was calculated (EDR for patients; EDR_p). The total dose of the rectum was calculated as the biologically equivalent dose in 2-Gy fractions (EQD₂). The associations between EDR_p for D_0.1cc, D_2cc, and D_5cc and the respective rectal EQD₂ values with late rectal complications were then analyzed. The median follow-up period was 40 months. Patients with rectal complications of ≥Grade 1 received a significantly higher mean EDR_p for D_0.1cc–5cc and had a greater EQD₂ for D_0.1cc–5cc. Multivariate analysis was performed using the mean EDR_p for D_2cc, EQD₂ for D_2cc, heavy smoking and BMI. Of these four variables, mean EDR_p for D_2cc (HR = 3.38, p = 0.004) and EQD₂ for D_2cc (HR = 2.59, p = 0.045) emerged as independent predictors for late rectal complications. In conclusion, mean EDR_p and EQD₂ were associated with late rectal complications in patients treated with HDR CT-based IGBT for cervical cancer.     

Comparison of acute gastrointestinal toxicities between 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy including prophylactic regions in chemoradiotherapy with S-1 for pancreatic cancer—importance of dose volume histogram parameters in the stomach as the predictive factors-

The purpose of this study was to compare acute gastrointestinal (GI) toxicities in patients who underwent 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in chemoradiotherapy (CRT) with S-1 including prophylactic regions for pancreatic cancer. We also investigated the predictive factor of acute GI toxicities in dose volume histogram (DVH) parameters. Patients who received CRT with S-1 for pancreatic cancer between January 2014 and March 2021 were included. Radiotherapy (RT) with a total dose of 50-54 Gy was delivered. We examined the differences in the frequencies of acute GI toxicity of grade 2 or higher and DVH parameters of the stomach (ST) and duodenum (DU) between the 3DCRT group and the IMRT group. The RT-related predictive factors of acute GI toxicities were investigated by univariate and multivariate analyses. There were 25 patients in the 3DCRT group and 31 patients in the IMRT group. The frequencies of acute GI toxicity of G2 or higher were 36% in the 3DCRT group and 9.7% in the IMRT group (p = 0.035). ST V50 was the most predictive factor (p = 0.001), and the incidences of acute GI toxicity of G2 or higher in ST V50 ≥ 4.1 cc and < 4.1cc were 43.7% and 7.7%, respectively. ST V40 was also a significant predictive factor of acute GI toxicity (p = 0.002). IMRT could reduce acute GI toxicities in CRT with S-1 including prophylactic regions for pancreatic cancer. Acute GI toxicities may be affected by moderate to high doses to the ST.     

社会支持与宫颈癌患者生活质量的相关性分析

目的 了解宫颈癌患者社会支持与生活质量的特性,分析二者之间的相关性,探讨提高患者生活质量的有效途径.方法 分别用自行设计的一般情况问卷、生活质量核心问卷(EORTC QLQ-C30)、社会支持量表(SSRS)对2014年3至2016年3月在西安交通大学第一附属医院行综合性治疗的302例宫颈癌患者进行问卷调查.结果 宫颈癌患者生活质量较差;社会支持总分高于国内常模(t=4.308,P<0.001);社会支持与宫颈癌患者生活质量呈正相关(r=0.638,P<0.01).结论 宫颈癌患者的生活质量与社会支持密切相关,护理过程中要重视患者的社会支持,以提高患者的生活质量.     

3166例已婚妇女乳腺癌、宫颈癌为重点的妇科疾病筛查结果分析

目的通过农八师133团20～60岁本地户籍已婚妇女进行以＂乳腺癌、宫颈癌＂为重点的妇科病普查工作（以下简称＂两癌＂）,了解农八师133团妇女20～60岁生殖健康状况和妇科疾病发生率,分析发病因素,掌握发病原因,提高＂两癌＂的早诊、早治率,降低死亡率。方法对3166例用统一固定的体检表格进行基本情况及病史的询问填写,常规妇科检查、乳腺检查及辅助检查。结果乳腺癌2例,宫颈癌1例。妇科疾病患病总人数2350人,患病率74.2%,其中宫颈炎56.6%,乳腺疾病30%,阴道炎21.29%。结论妇女常见病以宫颈炎为主,乳腺增生有上升趋势。加强妇女保健宣传力度,增强妇女自我保健意识,坚持定期进行妇科病查治,提高生存质量。     

伊立替康联合顺铂与紫杉醇联合顺铂治疗宫颈癌的临床疗效分析

目的 比较伊立替康联合顺铂与紫杉醇联合顺铂治疗宫颈癌患者的临床疗效.方法 选择2012年1月至2015年12月在江汉大学附属医院进行中晚期宫颈癌治疗的患者76例,随机分为观察组和对照组,各38例.对照组使用紫杉醇联合顺铂(TP)方案进行治疗,观察组使用伊立替康联合顺铂(IP)方案进行治疗.观察两组患者临床疗效、治疗前后血清SCC-Ag、CD133水平变化以及不良反应发生情况.结果 观察组患者总有效率为89.47％,对照组为68.42％,观察组患者治疗后总有效率明显高于对照组,且具有统计学差异(x2=3.879,P＜0.05).肿瘤直径治疗前两组无明显差异(t=0.420,P＞0.05),治疗后均有所减小,而观察组减少的更为明显(t=3.442,P＜0.05).两组患者治疗前血清SCC-Ag、CD133水平无明显差异,治疗后观察组患者血清SCC-Ag水平(t=10.690,P＜0.05)和CD133阳性率明显低于对照组(x2=4.375,P＜0.05).观察组患者骨髓抑制、消化道反应、脱发、肝肾功能损害以及外周神经毒性等不良反应发生率均低于对照组,具有统计学差异(x2值分别为6.480、5.330、5.510、5.050、5.680,均P＜0.05).结论 伊立替康联合顺铂化疗对中晚期宫颈癌患者具有良好的临床疗效,能够显著降低患者血清SCC-Ag、CD133水平,且不良反应小,安全可靠.