Central Shield Research Articles

Role of the gel spacer in safely delivering whole pelvic radiation therapy without central shielding in computed tomography-based image-guided adaptive brachytherapy for uterine cervical cancer patients

BackgroundTo protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥ 85 Gy to high-risk clinical target volume D90 (CTVHR D90%). In this study, we investigated whether a gel spacer can enable the safe delivery of the ESTRO/ABS-recommended doses to the target while observing dose constraints for the OARs without using CS in external beam radiation therapy (EBRT). Materials and MethodsTwenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between April 2017 and May 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy expressed in the form of the equivalent dose in 2 Gy fractions (EQD2) were calculated. Treatment outcomes and incidence of adverse events were also examined. ResultsThe median cumulative CTVHR D90%, rectum D2cm3, and bladder D2cm3 were 86.6 Gy (range, 69.8–103.7), 62.9 Gy (range, 55.3–72.5), and 72.0 Gy (range, 62.9–84.1), respectively. The median follow-up was 35.9 months (range, 10.9–70.3). The 2-year local control rate was 95% (95% CI: [69–99%]). There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events. ConclusionsThe use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates.

A new monitoring method for control rods position of small modular reactors (SMRs)-based coaxial capacitor

The position of control rods is one of the core parameters that can affect the power of nuclear reactors, and it is needed to be monitored by the position indicators. Based on the central shielding effect of the driving rod, the design of the coaxial capacitive position indicators is proposed in this paper. The theoretical rod position recognition model of the indicator is constructed by the conformal mapping, and it is verified by the numerical method. The results manifest that the performance of the indicator can be accurately analyzed by the theoretical model. The performance of the indicator is studied, and it is compared with that of the existing capacitive position indicator. The results show that compared with the existing design, the precision and the sensitivity of the new indicator can be enhanced by two orders of magnitude at the same time.

Evaluating dose distributions of high dose rate 60Co brachytherapy in an asymmetric tumor: A comparison of different designs of vaginal cylindrical applicators

The aim of this study is to evaluate organ-at-risk (OAR) doses obtained from different designs of intracavitary cylinder applicators during high-dose-rate (HDR) brachytherapy of an asymmetric vaginal tumor. Dose distributions around five cylinder applicators were obtained using the Geant4 toolkit. Three of these applicators are commercially available: single-channel, multi-channel, and shielded. Additionally, two proposed sub-configurations were evaluated: (I) a combination of the multichannel applicator with a central shield and (II) a dynamically modulated cylinder (DMC). The dose distributions of the proposed applicators were compared to those of the single-channel cylinder applicator. The results showed that using a cylindrical applicator with a higher degree of freedom in plan optimization can improve OAR, sparing up to 60% for the rectum and 20% for the bladder. In conclusion, this work suggests using a new design of a cylindrical applicator to enhance the therapeutic ratio of brachytherapy for asymmetric and irregularly shaped vaginal tumors.

Intensity-modulated radiation therapy with the central shielding technique for patients with uterine cervical cancer

Abstract We aimed to examine outcomes and toxicities of intensity-modulated radiation therapy (IMRT) with the central shielding (CS) technique for patients with uterine cervical cancer. This retrospective study included 54 patients with International Federation of Gynecology and Obstetrics IB-IVA cancer. Whole pelvic radiotherapy or extended-field radiotherapy were performed at the dose of 50.4 Gy in 28 fractions with helical tomotherapy (HT). Six patients had para-aortic lymph node metastases. The CS technique with HT was utilized after a total dose of 28.8–41.4 Gy to reduce doses to the rectum and bladder. The prescribed dose of intracavitary brachytherapy was mainly 18–24 Gy in three or four fractions at point A. Concurrent chemotherapy was used for 47 patients (87%). Median follow-up time was 56 months. Seventeen patients (31%) developed recurrence. The recurrence of the cervix was observed in two patients (4%). The 5-year rates of the locoregional control, progression-free survival (PFS) and overall survival were 79, 66 and 82%, respectively. Among several factors evaluated, histological type of adenocarcinoma was only a significantly worse prognostic factor for PFS by multivariate analysis (hazard ratio, 4.9 [95% confidence interval, 1.3–18], P = 0.018). Grade 2 or higher late toxicities were observed in nine patients (17%). Two patients (4%) each had grade 3 proctitis and grade 3 ileus, respectively. No grade 4 toxicity or treatment-related death was observed. The results suggest that IMRT with the CS technique allows a high local control without increasing the risk of complications for cervical cancer patients.

Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range.

To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy. The study included 167 patients (T1+2=108, T3+4=59) from eight Japanese institutions. For three-dimensional-image-guided brachytherapy, intra-cavitary and interstitial brachytherapy was utilized in 33 patients (20%). The median follow-up was 26.6months (interquartile range, 20-43.2). The maximum rectal D2 (75Gy)/bladder D2 (90Gy) constraints were deviated by 6%/10% and 10%/5% for T1+2 and T3+4, respectively. The 2-year incidence of ≥grade 3 proctitis/cystitis was 4%/1% for T1+2 and 10%/2% for T3+4. The 2-year local progression-free survival was 89% for T1+2 and 82% for T3+4. For T1+2, the 2-year local progression-free survival for the high-risk clinical target volume D90≥68Gy (indicated by receiver operating characteristic analysis; area under the curve=0.711) was 92% versus 67% for <68Gy (log-rank; P=0.019). Cox multivariate analysis indicated that the high-risk clinical target volume D90 was one of independent predictors of local failure (P=0.0006). For T3+4, the 2-year local progression-free survival was 87% for the high-risk clinical target volume <82cm3 (area under the curve=0.67) and 43% for ≥82cm3 (P=0.0004). Only the high-risk clinical target volume was an independent predictor of local failure (P=0.0024). Definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy was feasible for Japanese patients with cervical cancer. Dose de-escalation from the current global standards is suggested for patients with T1+2 disease.

CT-based image-guided brachytherapy in uterine cervical cancer: Effect of tumor dose and volume on local control

To determine the optimal primary tumor dose for cervical cancer treatment using computed tomography (CT)-based image-guided brachytherapy (IGBT). We retrospectively reviewed 171 patients with cervical cancer who underwent both external beam radiation therapy (EBRT) and IGBT between May 2015 and December 2019. Majority of EBRT plan included central shielding technique. CT-based IGBT was performed weekly a median of three times. Magnetic resonance imaging preceded the first and third session of IGBT for target delineation. The median age of the patients was 64 years (range: 30-91 years). The median follow-up time for living patients was 43 months (range: 6-76 months). The 3-year local control rates according to the International Federation of Gynecology and Obstetrics (FIGO, 2008) stages were 89%, 100%, 92%, 89%, 78%, and 100% for stages IB, IIA, IIB, IIIA, IIIB, and IVA, respectively. The median EBRT dose to the central pelvis and parametrium/pelvic wall was 41.4 Gy and 50.4 Gy, respectively. Patients who received a cumulative 2 Gy equivalent dose (EQD2) (α/β = 10 Gy) of high-risk clinical target volume (HR CTV) D90% ≥ 75 Gy achieved a long-term local control rate of 93%, compared with 80% in those who received <75 Gy (p = 0.02). This is one of the largest CT-based IGBT series examining the treatment of cervical cancer based on the tumor dose-volume relationship. An HR CTV D90% ≥75 Gy was significantly associated with favorable local control in this study.

Results of computer tomography-based adaptive brachytherapy in combination with whole-pelvic- and central-shielding-external beam radiotherapy for cervical cancer

To evaluate treatment results and investigate predictors of local control. In this retrospective study of 236 patients with cervical cancer, we administered CT-based adaptive brachytherapy (BT) in combination with whole- pelvic (WP)- and central shielding (CS)- external beam radiotherapy (EBRT) with or without chemotherapy. The study cohort comprised patients with cervical cancer treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy between June 2013 and March 2019. Local control (LC), overall survival (OS), and late toxicity were evaluated. Predictive factors for LC were analyzed by univariate and multivariate analyses. Median doses of WP- and CS-EBRT and BT were 30.6 GyEQD2, 19.8 GyEQD2, and 40.3 GyEQD2, respectively. The 3-year LC rates for T1b2, T2a, T2b, T3b, and T4 were 100%, 100%, 97.3%, 86.9%, and 91.7%, respectively (p = 0.346). The 3-year OS for Stages IB, IIB, IIIB, IIIC, and IVA were 100%, 94.8%, 82.5%, 81.7%, and 74.6%, respectively (p = 0.037). Rates of Grade 3-4 gastrointestinal and genitourinary toxicities were 3.8% and 1.7%, respectively. Multivariate analysis showed that T3-4, nonsquamous cell histology, and high-risk clinical target volume (CTVHR) D90 of BT < 36GyEQD2 were independently associated with significantly poorer LC. The combination of WP- and CS-EBRT and CT-based IGBT with or without concurrent chemotherapy produced favorable LC outcomes with low rates of late toxicities for patients with small or medium-sized tumors. However, LC was less favorable for patients who had large T3 disease, and the use of CS requires caution in these patients.

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.

PO-1355 The treatment strategy for cervical cancer; image-guided HDR-ICBT and IMRT using central shielding

PO-1355 The treatment strategy for cervical cancer; image-guided HDR-ICBT and IMRT using central shielding

Dosimetric feasibility of computed tomography-based image-guided brachytherapy in locally advanced cervical cancer: a Japanese prospective multi-institutional study.

ABSTRACTThe aim of this study was to assess the feasibility of planning dose–volume histogram (DVH) parameters in computed tomography-based 3D image-guided brachytherapy for locally advanced cervical cancer. In a prospective multi-institutional study, 60 patients with stage IIA2–IVA cervical cancer from eight institutions were treated with external beam radiotherapy using central shielding and intracavitary or hybrid (combined intracavitary/interstitial) brachytherapy (HBT). The dose constraints were set as a cumulative linear quadratic equivalent dose (EQD2) of at least 60 Gy for high-risk clinical target volume (HR-CTV) D90, D2cc ≤ 75 Gy for rectum, D2cc ≤ 90 Gy for bladder and D2cc ≤ 75 Gy for sigmoid. The median HR-CTV D90 was 70.0 Gy (range, 62.8–83.7 Gy) in EQD2. The median D2cc of rectum, bladder and sigmoid was 57.1 Gy (range, 39.8–72.1 Gy), 68.9 Gy (range, 46.5–84.9 Gy) and 57.2 Gy (range, 39.2–71.2 Gy) in EQD2, respectively. In 76 of 233 sessions (33%), 23 patients underwent HBT, and the median number of interstitial needles was 2 (range, 1–5). HBT for a bulky HR-CTV (≥40 cm3) significantly improved the HR-CTV D90 compared with intracavitary brachytherapy alone (P = 0.010). All patients fulfilled the dose constrains for target and at risk organs by undergoing HBT in one-third of sessions. We conclude that the planning DVH parameters used in our protocol are clinically feasible.

Local Control of Squamous Cell Carcinoma of the Cervix Treated with CT-based Three-dimensional Image-Guided Brachytherapy with or without Central Shielding.

The purposes of this retrospective study were to analyze local control of squamous cell carcinoma of the cervix treated with computed tomography (CT)-based image-guided brachytherapy (IGBT), as well as the factors affecting local control. A total of 39 patients were analyzed. The prescribed dose to the pelvis was 45-50 Gy with or without central shielding (CS). IGBT was delivered in 1-5 fractions. The total dose for high-risk clinical target volume (HR-CTV) was calculated as the biologically equivalent dose in 2-Gy fractions. The median follow-up period was 29.3 months. The 2-year overall survival and local control rates were 97% and 91%, respectively. In univariate analysis, the dose covering 90% of the HR-CTV (D90) and tumor size were found to be significant factors for local control. The cutoff values of tumor size and D90 for local control were 4.3 cm (area under the curve [AUC] 0.75) and 67.7 Gy (AUC 0.84) in the CS group and 5.3 cm (AUC 0.75) and 73.7 Gy (AUC 0.78) in the group without CS, respectively. However, though the local control of CT-based IGBT was favorable, the results suggested that the dose required for tumor control may differ depending on the presence of CS.

Разработка вакуумной дугогасительной камеры для одноразрывного вакуумного выключателя на 110 кВ

Requirements for high-voltage vacuum circuit breakers for networks with a grounded neutral, which are stemming from the prospects of using vacuum circuit breakers in networks with the solidly grounded neutral are formulated. The arch chute design for a 110 kV single-break vacuum circuit breaker that takes into account the occurrence of repeated breakdowns is developed. The shielding system equalizes the voltage over the chute casing, decreases the electric field intensity at the “triple point”, protects the casing dielectric from becoming dusted with metallic contact parts erosion products, prevents the occurrence of cascade breakdown between the contact parts and central shield, and eliminates a possible decrease of the chute electric strength as it gradually works out its switching life. It is shown that the chute design includes measures to prevent the possibility of repeated breakdowns during disconnection up to class С1 according to GOST 52565-2006. It has been proven that for vacuum arc chutes for class С2 (for switching a capacitive load) it is necessary to develop a chute with two breaks between the contact parts or to connect two vacuum chutes in series. The shielding system adopted in the chute rules out the possibility of ceramic casing to become metallized, which decreases the chute electric strength as it gradually works out its switching life, and the vacuum arc transfer to beyond the inter-contact gap boundaries onto the central shield, the burnout of which results in that the vacuum arc chute loses its tightness and fully loses its functional properties.

Definitive radiotherapy consisting of whole pelvic radiotherapy with no central shielding and CT-based intracavitary brachytherapy for cervical cancer: feasibility, toxicity, and oncologic outcomes in Japanese patients

BackgroundThis prospective study investigated the feasibility, toxicity, and oncologic outcomes of definitive radiotherapy (RT) consisting of whole pelvic radiotherapy with no central shielding (noCS-WPRT) and CT-based intracavitary brachytherapy (ICBT) in Japanese patients with cervical cancer.MethodsPatients with cervical cancer of FIGO stages IB1–IVA were eligible. The treatment protocol consisted of noCS-WPRT of 45 Gy in 25 fractions and CT-based high dose-rate ICBT of 15 or 20 Gy in 3 or 4 fractions prescribed at point A. The prescribed ICBT dose was decreased if the manual dwell time/position optimization failed to meet organs-at-risk constraints. Graphical optimization and additional interstitial needles were not applied.ResultsWe enrolled 40 patients. FIGO stages were IB1: 11, IB2: 13, IIA2: 1, IIB: 11, IIIB: 3, and IVA: 1. Median (range) pretreatment tumor diameter was 47 (14–81) mm. Point A doses were decreased in 19 of 153 ICBT sessions (12%). The median follow-up duration was 33 months. The 2-year rates of pelvic control, local control (LC), and progression-free survival were 83%, 85%, and 75%, respectively. Pre-ICBT tumor diameter, high-risk clinical target volume (HR-CTV), total HR-CTV D90, and overall treatment time (OTT) significantly affected LC. Late adverse events (grade ≥ 3) were observed in 3 patients (2 in the bladder, 1 in the rectum).ConclusionsDefinitive RT consisting of noCS-WPRT and CT-based ICBT was feasible for Japanese patients with cervical cancer. To further improve LC, additional interstitial needles for patients with a large HR-CTV and shorter OTT should be considered.

Preliminary survey of 3D image-guided brachytherapy for cervical cancer at representative hospitals in Asian countries

3D image-guided brachytherapy (3D-IGBT) has become a standard therapy for cervical cancer. However, the use of 3D-IGBT is limited in East and Southeast Asia. This study aimed to clarify the current usage patterns of 3D-IGBT for cervical cancer in East and Southeast Asia. A questionnaire-based survey was performed in 11 countries within the framework of the Forum for Nuclear Cooperation in Asia. The questionnaire collected the treatment information of patients with cervical cancer who underwent 3D-IGBT. The cumulative external beam radiotherapy and 3D-IGBT doses were summarized and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2) using a linear-quadratic model. Of the 11 institutions representing the participating countries, six (55%) responded to the questionnaire. Overall, data of 36 patients were collected from the six institutions. Twenty-one patients underwent whole-pelvic irradiation and 15 underwent whole-pelvic irradiation with central shielding. Patients received a median of four treatment sessions of 3D-IGBT (range, 2–6). All 3D-IGBT sessions were computed tomography (CT)-based and not magnetic resonance image-based. The median doses to the high-risk clinical target volume D90, bladder D2cc, rectum D2cc and sigmoid colon D2cc were 80.9 Gy EQD2 (range, 58.9–105.9), 77.7 Gy EQD2 (range, 56.9–99.1), 68.0 Gy EQD2 (range, 48.6–90.7) and 62.0 Gy EQD2 (range, 39.6–83.7), respectively. This study elucidated the current patterns of 3D-IGBT for the treatment of cervical cancer in East and Southeast Asia. The results indicate the feasibility of observational studies of CT-based 3D-IGBT for cervical cancer in these countries.

Plan-Optimization Method for Central-shielding Pelvic Volumetric-modulated Arc Therapy for Cervical Cancer.

To establish a method of plan optimization in pelvic volumetric-modulated arc therapy (VMAT) for cervical cancer using the central-shielding (CS) principle. We created external beam VMAT plans for eight cases with non-bulky stage I-IIb using the CS principle based on the Japanese standard guideline. Clinical target volumes (CTVs) for whole-pelvis (WP) irradiation were created using published guidelines, and CTVs for CS irradiation were created by subtracting the uterus corpus and 4 cm-wide regions centered at the cervix and vagina from the CTVs for WP irradiation. For plan optimization of CS irradiation, a 4-cm diameter cylindrical volume centered in the cervix and vagina was created as the volume receiving a high dose in brachytherapy, and the volume overlapping with the rectum was defined as the Ant-Rectum. Dose-volume histogram (DVH) parameters of two CS VMAT plans with and without (VMATOPT/VMATNO) dose optimization to the Ant-Rectum were compared. VMATOPT plans resulted in significantly lower DVH parameters of the Ant-Rectum and rectum compared to VMATNO plans. These were comparable to the DVH parameters of three-dimensional conformal radiotherapy (3DCRT) plans. Both VMAT plans resulted in significantly better coverage of planning target volumes than did the 3DCRT plans. In the implementation of IMRT/VMAT as the standard treatment for cervical cancer in Japan, our optimization method may be an essential step toward fully benefitting from the CS principle.

Multi-Institutional Observational Study of Prophylactic Extended-Field Concurrent Chemoradiotherapy Using Weekly Cisplatin for Patients with Pelvic Node-Positive Cervical Cancer in East and Southeast Asia

This multi-institutional observational study conducted among 11 Asian countries aimed to assess the clinical outcomes of prophylactic extended-field concurrent chemoradiotherapy using weekly cisplatin for patients with locally advanced cervical cancer in East and Southeast Asia. Uterine cervical cancer is among the most common cancers in East and Southeast Asia, and the mortality rate remains high in these countries because many patients present at a relatively advanced stage. It is necessary to develop new treatment methods for locally advanced cervical cancer suitable for developing countries. The pattern of spread in cervical cancer appears to be orderly, initially involving the low pelvis and then progressing to high pelvic lymph nodes (PLN) and para-aortic lymph nodes (PALN). To control occult PALN metastasis, extended-field radiation therapy including the para-aortic region and PLN region may be one of the effective treatments. Between October 2007 and May 2016, 106 patients with untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiotherapy consisted of pelvic irradiation (total dose, 50 Gy/25 fractions including central shielding), prophylactic para-aortic regional irradiation (36-40 Gy/20 fractions), and either high- or low-dose-rate intracavitary brachytherapy (ICBT) according to institutional practice. The planned Point A dose was 21-28 Gy in 3-4 fractions for high-dose-rate ICBT and 40-41 Gy in 1-2 fractions for low-dose-rate ICBT. Five cycles of weekly cisplatin (40 mg/m2) were administered during the radiotherapy course. A total of 106 patients were enrolled. Of these, 10 had major protocol violations and 2 did not receive treatment because of worsened general condition. Thus, 95 patients were evaluable. The median follow-up was 56 months. Of the 95 patients, 76 (80%) received four or five cycles of chemotherapy. Acute grade 3 leukopenia was observed in 20 (21%) of the patients, and late grade 3 gastrointestinal toxicity was observed in 3%. The 2-year local control, progression-free survival, and overall survival rate for all patients were 96%, 78%, and 90%, respectively. The results indicated that prophylactic extended-field concurrent chemoradiotherapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.

Single-Institution Experience in 3D MRI/CT-Based Brachytherapy for Cervical Cancer

Although use of magnetic resonance imaging (MRI) has demonstrated superiority in target volume delineation, it is not routinely offered in brachytherapy centers because of the lack of MRI accessibility. In order to exploit the full potential of CT and MRI, we have previously reported that patients in our center are routinely treated with image-guided brachytherapy (IGBT) using a combined MRI/CT-based approach with an MRI only at the time of the first brachytherapy session. The purpose of the current retrospective study was to evaluate patients’ outcome in cervical cancer treated by MRI/CT-based IGBT. A chart of 109 patients with cervical cancer who received definitive radiation therapy between July 2014 and Dec 2017 were retrospectively reviewed. The median age was 61 years (range: 29-86). Eighty-nine patients were squamous cell carcinoma, 14 patients were adenocarcinoma, and six patients were other types of pathology. FIGO stages were I-IIA/IIB/IIIA/IIIB-IV=49/20/2/38. Twenty-three patients who had para-aortic lymph node metastases were treated with extended-field external beam radiotherapy which covers para-aortic lymph node and pelvic lymph node. Concurrent chemotherapy (CDDP) was administered in 90 patients. Central shielding method was used in external beam radiotherapy. The median dose of total pelvic side wall was 50 Gy (36-56). The initiation of CS was median 30 Gy (20-50). Overall survival rate (OS), progression free survival (PFS), and local control rate (LCR) were calculated by the Kaplan–Meier method. Effects of clinical/treatment factors on LCR, OS, and PFS were statistically analyzed. The median value of high-risk clinical target volume (HR-CTV) at the first IGBT was 25.3 mm3 (range: 7.64-139.8 mm3). The median prescribed dose to HR-CTV D90 was 74.8 Gy (range: 39.5 - 108.6 Gy). The overall treatment time was 44 days (range: 28 - 57 days). With a median follow-up of 28 months (range: 1-53 months), the 2-year overall survival (OS), progression-free survival (PFS), and local control rates (LCR) for all patients were 90.0%, 77.4% and 92.8%, respectively. On univariate analysis, LCR was significantly higher in patients with HR-CTV volume of 35 mm3 or smaller (87.5% vs. 100% at 2-year, p = 0.007). Both PFS and OS was significantly unfavorable in those patients with adenocarcinoma (p<0.0001 and p=0.0058, respectively). Concerning adverse events, Grade 3 or higher adverse events were observed in 3 patients. Hematuria (Grade 3) was observed in 1 patient, radiation proctitis was in 1 patient, fracture of pubic bone (Grade 2) was in 1 patient, lymphedema (Grade 3) was in 1 patient, and ileus (Grade 3) was in 2 patients. Although our series included relatively advanced disease (stage III or advanced in 40 patients, PAN+ in 23), favorable results with minor adverse events could be obtained by MRI/CT-based IGBT. The HR-CTV volume at the first brachytherapy session of greater than 35 mm3 had adverse impact on local control.

Dose-volume parameters and local tumor control in cervical cancer treated with central-shielding external-beam radiotherapy and CT-based image-guided brachytherapy.

Definitive radiotherapy for cervical cancer consists of external-beam radiotherapy (EBRT) and brachytherapy. In EBRT, a central shield (CS) reduces the dose to the rectum and bladder. The combination of whole-pelvic (WP)- and CS-EBRT and brachytherapy is the standard radiotherapy protocol in Japan. Despite clinical studies, including multi-institutional clinical trials, showing that the Japanese treatment protocol yields favorable treatment outcomes with low rates of late radiation toxicities, dose–volume parameters for the Japanese treatment protocol remain to be established. We conducted a retrospective dose–volume analysis of 103 patients with uterine cervical cancer treated with the Japanese protocol using computed tomography–based adaptive brachytherapy. The 2-year overall survival and 2-year local control rates according to FIGO stage were 100% and 100% for Stage I, 92% and 94% for Stage II, and 85% and 87% for Stage III–IV, respectively. Late adverse effects in the rectum and bladder were acceptable. Receiver operating characteristic analysis discriminated recurrence within the high-risk clinical target volume (HR-CTV) (n = 5) from no local recurrence (n = 96), with the optimal response obtained at a dose of 36.0 GyEQD2 for HR-CTV D90 and 28.0 GyEQD2 for HR-CTV D98. These values were used as cut-offs in Fisher exact tests to show that high HR-CTV D90 and HR-CTV D98 doses for brachytherapy sessions were significantly associated with tumor control within the HR-CTV. These data suggest a contribution of brachytherapy to local tumor control in WP- and CS-EBRT and brachytherapy combination treatment, warranting validation in multi-institutional prospective studies.

Multi-institutional Observational Study of Prophylactic Extended-Field Concurrent Chemoradiation Therapy Using Weekly Cisplatin for Patients With Pelvic Node-Positive Cervical Cancer in East and Southeast Asia

This multi-institutional observational study conducted among 11 countries in East and Southeast Asia aimed to assess the clinical outcomes of prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin for patients with locally advanced cervical cancer. Between October 2007 and May 2016, 106 patients with untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiation therapy consisted of pelvic irradiation (total dose, 50 Gy in 25 fractions including central shielding), prophylactic paraortic regional irradiation (36-40 Gy in 20 fractions), and either high- or low-dose-rate intracavitary brachytherapy (ICBT) according to institutional practice. The planned point A dose was 21 to 28 Gy in 3 to 4 fractions for high-dose-rate ICBT and 40 to 41 Gy in 1 to 2 fractions for low-dose-rate ICBT. Five cycles of weekly cisplatin (40 mg/m2) were administered during the radiation therapy course. A total of 106 patients were enrolled. Of these, 9 had major protocol violations and 2 did not receive treatment because of worsened general condition. Thus, 95 patients were evaluable. The median follow-up was 56 months. Of the 95 patients, 76 (80%) received 4 or 5 cycles of chemotherapy. Acute grade 3 leukopenia was observed in 20 of the patients (21%), and late grade 3 gastrointestinal toxicity was observed in 3%. The 2-year local control, progression-free survival, and overall survival rate for all patients were 96%, 78%, and 90%, respectively. The results indicated that prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.

A 3-year follow-up study of radiotherapy using computed tomography–based image-guided brachytherapy for cervical cancer

Outcomes for patients with Stage IB1–IVA cervical cancer treated with computed tomography (CT)-based image-guided brachytherapy (IGBT) were examined in this study. A total of 84 patients were analyzed between March 2012 and June 2015. Whole-pelvic radiotherapy with a central shield was performed for each patient, and the total pelvic sidewall dose was 50 Gy. IGBT was delivered in 2–4 fractions. The initial prescription dose (6.8 Gy) was delivered at Point A, and the dose distribution was modified manually by graphical optimization. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions (EQD2). Concurrent chemotherapy was administered to 64 patients (76%). The median follow-up period was 36 months (range 2–62 months). The 3-year overall survival, local control, and progression-free survival rates were 94%, 89% and 81%, respectively. The mean EQD2 for HR-CTV D90 was 73.4 Gy, and the EQD2 for HR-CTV D90 was not significantly associated with the local control rate. In multivariate analysis, adenocarcinoma (P = 0.03) and tumor size ≥45 mm (P = 0.06) were risk factors for local control. The patients were divided into four groups based on histology (squamous cell carcinoma vs adenocarcinoma) and tumor size (<45 vs ≥45 mm). Those with large adenocarcinomas had significantly worse outcomes. In conclusion, CT-based IGBT achieved favorable local control, but different treatment strategies may be necessary for large adenocarcinomas.