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.     

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.     

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.     

Ⅰ_B期及Ⅱ_A期宫颈癌术前介入化疗与术前放疗的疗效观察

目的:比较ⅠB及ⅡA期宫颈癌术前介入化疗或放疗联合根治手术的疗效,探讨该期宫颈癌患者适宜的治疗方法。方法:选择温州医学院附属第二医院妇产科1998年5月～2003年5月收治的ⅠB和ⅡA期宫颈癌患者138例,所有患者肿瘤均>2cm。按FIGO分期,ⅠB1期24例,ⅠB2期48,ⅡA期66例;按肿瘤大小分为非巨块型(肿瘤直径2～4cm)53例,巨块型(肿瘤直径≥4cm)85例;术前介入化疗74例(化疗组),术前腔内放疗64例(放疗组)。对两组的近期疗效、术后病理组织学变化及中远期疗效进行比较。结果:非巨块型病例化疗组有效率为89.3%,稍高于放疗组88.0%,两组间差异无统计学意义(P>0.05)。巨块型病例化疗组有效率为84.8%,高于放疗组71.8%(P<0.05)。术后病理组织学比较,化疗组淋巴结转移率21.6%,深肌层浸润率21.6%,均低于放疗组的32.8%和34.4%(均P<0.05)。两组宫旁、阴道切缘浸润率及脉管癌栓比较差异无统计学意义(P>0.05)。非巨块型病例化疗组2年复发率为8.8%,5年生存率为83.2%,分别与放疗组10.1%及79.5%比较差异均无统计学意义(P>0.05);巨块型病例化疗组2年复发率为22.5%,5年生存率为81.4%,分别与放疗组31.9%及68.6%比较,均有统计学意义(P<0.05)。结论:巨块型ⅠB和ⅡA期宫颈癌术前应用介入化疗较术前放疗为佳;非巨块型病例术前介入化疗与术前放疗疗效相似。     

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.     

Dose reduction trial from 60 Gy in 10 fractions to 54 Gy in 9 fractions schedule in high-dose-rate interstitial brachytherapy for early oral tongue cancer

To compare the effects of 60 Gy/10 fractions (twice a day) with those of 54 Gy/9 fractions in high-dose-rate interstitial brachytherapy (HDR-ISBT) for early tongue cancer, we performed a matched-pair analysis of patients with early tongue cancer (T1-2N0M0), who were treated with 60 or 54 Gy of radiation between 1996 and 2004. Seventeen patients treated with 54 Gy and 34 matched-pair patients treated with 60 Gy were extracted and analyzed. Local recurrence occurred in two patients in the 54-Gy arm and five patients in the 60-Gy arm. The 2-year local control rates were 88% for both the 54-Gy arm and 60-Gy arm (not significant). The 2-year overall survival rates were 88% in the 60-Gy arm and 82% in the 54-Gy arm. Two-year actuarial complication-free rates were 91% in the 60-Gy arm and 83% in the 54-Gy arm (not significant), respectively. There was no significant association between the total dose and local control rate and late complications. The outcome of 54 Gy/ 9 fractions was similar to that of 60 Gy/ 10 fractions in patients with early tongue cancer.     

External beam boost irradiation for clinically positive pelvic nodes in patients with uterine cervical cancer

The purpose of this study was to retrospectively analyze the treatment results of boost external beam radiotherapy (EBRT) to clinically positive pelvic nodes in patients with uterine cervical cancer. The study population comprised 174 patients with FIGO stages 1B1–4A cervical cancer who were treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients with positive para-aortic or common iliac nodes (≥10 mm in the shortest diameter, as evaluated by CT/MRI) were ineligible for the study. Fifty-seven patients (33%) had clinically positive pelvic nodes. The median maximum diameter of the nodes was 15 mm (range, 10–60 mm) and the median number of positive lymph nodes was two (range, one to four). Fifty-two of 57 patients (91%) with positive nodes were treated with boost EBRT (6–10 Gy in three to five fractions). The median prescribed dose of EBRT for nodes was 56 Gy. The median follow-up time for all patients was 66 months (range, 3–142 months). The 5-year overall survival rate, disease-free survival rate and pelvic control rate for patients with positive and negative nodes were 73% and 92% (P = 0.001), 58% and 84% (P < 0.001), and 83% and 92% (P = 0.082), respectively. Five of 57 node-positive patients (9%) developed pelvic node recurrences. All five patients with nodal failure had concomitant cervical failure and/or distant metastases. No significant difference was observed with respect to the incidence or severity of late complications by application of boost EBRT. The current retrospective study demonstrated that boost EBRT to positive pelvic nodes achieves favorable nodal control without increasing late complications.     

宫颈癌调强放疗骨盆受照射剂量与骨髓抑制的临床研究

目的 研究宫颈癌调强放疗时骨盆受照射剂量、体积与急性骨髓抑制的相关性,探讨放射治疗中骨盆骨髓保护的必要性,降低急性骨髓抑制发生率,提高患者的生活质量。方法 选取在徐州医科大学附属医院放射治疗科行盆腔调强放疗的80例宫颈癌患者,根据有无发生≥2级急性骨髓抑制,分为急性骨髓抑制组(试验组)40例、无骨髓抑制组(对照组)40倒。比较2组间骨盆剂量体积参数(Dmax、Dmean、V5、V10、V15、V20、V30、V40、V50)与≥2级急性骨髓抑制的相关性。结果 急性骨髓抑制组骨盆Dmax、Dmean、V5、V10、V15、V20、V30、V40高于无骨髓抑制组,2组间Dmean、V5、V10、V15、V20差异有统计学意义(t分别=2.365、2.157、2.127、2.251、4.800,P<0.05)。结论 盆体外照射时急性骨髓抑制与骨盆受照射剂量、体积有关,骨盆对放射线较敏感,应注意保护。     

调强放疗联合化疗治疗宫颈癌盆腔复发的临床研究

目的探讨调强放疗联合化疗治疗宫颈癌盆腔复发的近期疗效及并发症的发生情况。方法对25例盆腔复发的宫颈癌患者,采用盆腔调强放疗联合DDP同步化疗的方法,给予患者处方剂量95%PTV:50～60Gy/25～30次/2Gy/次,放疗期间同步DDP周方案化疗,观察患者的临床疗效及不良反应。结果所有患者均完成调强放疗,阴道出血缓解率为88.9%(16/18),下肢浮肿缓解率为88.2%(15/17),腰腿疼痛缓解率为86.4%(19/22)。3个月后疗效评估,完全缓解率为52%(13/25),部分缓解率为24%(6/25),稳定率为8%(2/25),进展率为16%(4/25),有效率为76%(19/25)。近期不良反应主要为骨髓抑制、胃肠道反应及泌尿系统反应,≥Ⅲ度骨髓抑制发生率为12%(3/25),胃肠道反应和泌尿系统反应为Ⅰ～Ⅱ级,发生率分别为36%(9/25)、32%(8/25),未发生Ⅲ级及以上胃肠道反应及泌尿系统反应。结论调强放疗联合化疗治疗宫颈癌盆腔复发,能缓解患者症状,近期疗效好,不良反应可耐受。     

Impact of boost irradiation on pelvic lymph node control in patients with cervical cancer

Radiation therapy (RT) for metastatic pelvic lymph nodes (PLNs) is not well established in cervical cancer. In this study the correlation between size of lymph nodes and control doses of RT was analyzed. Between January 2002 and December 2007, 245 patients with squamous cell carcinoma of the cervix treated with a combination of external beam irradiation with or without boost irradiation and high-dose rate brachytherapy were investigated. Size of lymph node was measured by computed tomography before RT and just after 50 Gy RT. Of the 245 patients, 78 had PLN metastases, and a total of 129 had enlarged PLNs diagnosed as metastases; 22 patients had PLN failure. The PLN control rate at 5 years was 79.5% for positive cases and 95.8% for negative cases. In cases with positive PLNs, 12 of 129 nodes (9.3%) developed recurrences. There was significant correlation between PLN control rate and size of PLN after 50 Gy (<10 mm: 96.7%, ≥ 10 mm: 75.7 % (P<0.001)). In addition, the recurrence in these poor-response nodes was significantly correlated with dose of RT. Nine of 16 nodes receiving ≤ 58 Gy had recurrence, but none of 21 nodes receiving > 58 Gy had recurrence (P = 0.0003). These results suggested that the response of lymph nodes after RT was a more significant predictive factor for recurrence than size of lymph node before RT, and poor-response lymph nodes might require boost irradiation at a total dose of > 58 Gy.     

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.     

Treatment outcomes of patients with FIGO Stage I/II uterine cervical cancer treated with definitive radiotherapy: a multi-institutional retrospective research study

The purpose of this study was to analyze the patterns of care and outcomes of patients with FIGO Stage I/II cervical cancer who underwent definitive radiotherapy (RT) at multiple Japanese institutions. The Japanese Radiation Oncology Study Group (JROSG) performed a questionnaire-based survey of their cervical cancer patients who were treated with definitive RT between January 2000 and December 2005. A total of 667 patients were entered in this study. Although half of the patients were considered suitable for definitive RT based on the clinical features of the tumor, about one-third of the patients were prescribed RT instead of surgery because of poor medical status. The RT schedule most frequently utilized was whole-pelvic field irradiation (WP) of 30 Gy/15 fractions followed by WP with midline block of 20 Gy/10 fractions, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) of 24 Gy/4 fractions prescribed at point A. Chemotherapy was administered to 306 patients (46%). The most frequent regimen contained cisplatin (CDDP). The median follow-up time for all patients was 65 months (range, 2–135 months). The 5-year overall survival (OS), pelvic control (PC) and disease-free survival (DFS) rates for all patients were 78%, 90% and 69%, respectively. Tumor diameter and nodal status were significant prognostic indicators for OS, PC and DFS. Chemotherapy has potential for improving the OS and DFS of patients with bulky tumors, but not for non-bulky tumors. This study found that definitive RT for patients with Stage I/II cervical cancer achieved good survival outcomes.     

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.     

Tumor size before image-guided brachytherapy is an important factor of local control after radiotherapy for cervical squamous cell carcinoma: analysis in cases using central shielding

We analyzed the local control (LC) of cervical squamous cell carcinoma treated by computed tomography (CT)-based image-guided brachytherapy (IGBT) using central shielding (CS). We also examined the value of tumor diameter before brachytherapy (BT) as a factor of LC. In total, 97 patients were analyzed between April 2016 and March 2020. Whole-pelvic (WP) radiotherapy (RT) with CS was performed, and the total pelvic sidewall dose was 50 or 50.4 Gy; IGBT was delivered in 3–4 fractions. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions, and distribution was modified manually by graphical optimization. The median follow-up period was 31.8 months (6.3–63.2 months). The 1- and 2-year LC rates were 89% and 87%, respectively. The hazard ratio was 10.11 (95% confidence interval: 1.48–68.99) for local recurrence in those with a horizontal tumor diameter ≥ 4 cm compared to those with < 4 cm before BT. In CT-based IGBT for squamous cell carcinoma, favorable LC can be obtained in patients with a tumor diameter < 4 cm before BT. However, if the tumor diameter is ≥ 4 cm, different treatment strategies such as employing interstitial-BT for dose escalation may be necessary.     

A multi-institutional survey of the quality of life after treatment for uterine cervical cancer: a comparison between radical radiotherapy and surgery in Japan

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.     

自身免疫细胞与放疗联合治疗对宫颈癌患者生活质量和免疫功能的影响

目的探讨自身免疫细胞与放疗联合治疗宫颈癌临床疗效,分析对宫颈癌患者生活质量及免疫功能的影响。方法选取2012年5月至2015年6月浙江大学医学院附属第二医院放疗科收治的85例宫颈癌患者为研究对象,分为对照组（n=42）和观察组（n=43）,对照组患者单纯放疗,观察组给予自身免疫细胞与放疗联合治疗,观察各组临床疗效,比较治疗前后两组患者免疫功能及治疗后生活质量。结果观察组总有效率为86.05%,对照组为64.28%,两组比较具有统计学差异（χ2=5.409,P=0.02）。对照组治疗后CD3＋、CD4＋、CD8＋细胞绝对值明显低于治疗前（t值分别为11.036、7.624、14.379,均P〈0.05）,观察组明显高于治疗前（t值分别为15.996、12.241、13.981,均P〈0.05）,治疗后两组CD3＋、CD4＋、CD8＋细胞绝对值比较有统计学差异（t值分别为22.758、20.839、27.140,均P〈0.05）。治疗后两组患者生存质量评分均明显高于治疗前（t对照组值分别为3.378、4.022、3.320、3.864,t观察组值分别为6.984、7.289、5.389、7.017,均P〈0.05）,观察组治疗后生存质量评分显著高于对照组（t值分别为3.609、3.386、3.009、4.417,均P〈0.05）。治疗后Ⅰ~Ⅱ期、Ⅲ~Ⅳ期两组患者生存质量评分均明显高于治疗前（tⅠ~Ⅱ期值分别为8.843、5.040、9.026、3.864,tⅢ~Ⅳ期值分别为5.534、5.314、9.604、10.210,均P〈0.05）,治疗后生存质量评分Ⅰ~Ⅱ期高于Ⅲ~Ⅳ期（t值分别为4.216、3.391、5.895、4.812,P〈0.05）。对照组出现骨髓抑制3例,消化道反应3例,观察组出现消化道反应3例,两组不良反应发生率比较无统计学差异（χ2=1.199,P=0.271）。结论自身免疫细胞与放疗联合治疗宫颈癌临床疗效显著,可通过提高患者免疫功能,提升患者生活质量。     

宫颈癌广泛性子宫切除术后引起尿潴留发生的危险因素分析

目的 探讨宫颈癌广泛性子宫切除术后引起尿潴留发生的危险因素.方法 回顾性分析2008年8月至2011年6月收治的行广泛性子宫切除术加盆腔淋巴结清扫术宫颈癌患者92例,分析术后尿潴留发生率及其相关危险因素.结果 92例患者中有31例术后出现尿潴留,发生率为33.70％.单因素分析表明,年龄、术中出血量、术后留置尿管时间、术后尿路感染与术后尿潴留有显著相关性(P＜0.05),而手术时间、临床分期、病理类型、术前辅助治疗、术后切口感染或脂肪液化与术后尿潴留无明显相关性(P＞0.05).多因素Logistic回归分析表明,年龄、术后留置尿管时间和术后尿路感染为影响术后尿潴留的危险因素.结论 年龄、术后留置尿管时间和术后尿路感染为影响广泛性子宫切除术后尿潴留的独立因素,采取综合措施适当缩短术后持续导尿时间,早期预防及控制尿路感染,是降低术后尿潴留的关键.