Naoya Murakami

Optimizing the planning process in computed tomography-based image-guided adaptive brachytherapy for cervical cancer using a spreadsheet-based daily dose management system

This study developed a system to reduce the treatment planning time for cervical cancer brachytherapy. An in-house Excel spreadsheet was developed to streamline dosimetric evaluation by combining external beam radiotherapy and brachytherapy doses, while also displaying daily dose constraints, a novel feature of the system. This system was validated in 46 consecutive patients who underwent intracavitary and interstitial brachytherapy using several applicators and required more complex dose calculation procedures than intracavitary brachytherapy alone. The proposed system included contouring and catheter reconstruction using multiple treatment planning systems simultaneously and was integrated with Excel spreadsheets for rapid dosimetric evaluation. The median time required for treatment planning was 36 min (range: 12-72 min), which was a much shorter time than those reported previously. This optimized system demonstrated the potential to increase the efficiency of brachytherapy planning to meet prescribed dose constraints without compromising treatment quality.

Gel spacer-assisted salvage brachytherapy for pelvic recurrence after definitive chemoradiotherapy in cervical cancer: A single-institution retrospective study

To evaluate the safety and efficacy of gel spacer-assisted high-dose-rate (HDR) salvage brachytherapy for pelvic recurrence after definitive chemoradiotherapy (CRT) for cervical cancer. We retrospectively analyzed 15 consecutive patients who underwent salvage HDR interstitial brachytherapy for pelvic recurrence following definitive CRT for cervical cancer between 2016 and 2024. Gel spacers were injected between the recurrent tumors and adjacent organs at risk (OARs), mainly the rectum and bladder, under transrectal ultrasound guidance at each brachytherapy session. The spacer's effectiveness was evaluated by comparing the hypothetical dose delivered to the gel spacer volume (assuming no spacer was used) with the actual dose to the OARs. The median biological equivalent dose in 2-Gy fractions (EQD2, α/β = 10) delivered during reirradiation was 64.0 Gy (range: 44.5-72.0 Gy). After a median follow-up of 22 months (range: 0-93 months), the complete response rate was 66.7% (10/15). Gel spacer injection significantly reduced the rectal D2cc by a median of 29% (interquartile range [IQR]: 14%-55%) and the bladder D2cc by 16% (IQR: 10%-34%) compared with the hypothetical dose estimates assuming no spacer use (Wilcoxon signed-rank test, p < 0.001). Grade ≥3 late toxicities occurred in only one patient (10.0%) among complete responders, and no spacer-related adverse events were observed. Gel spacer-assisted salvage brachytherapy significantly reduced radiation exposure to critical OARs, particularly the rectum, while achieving effective tumor control in patients with pelvic recurrence of cervical cancer after definitive CRT. These promising results support this approach as a feasible and safe strategy, warranting further validation in larger prospective studies.

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

To 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 D Twenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between 2017 and 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy treatment outcomes and incidence of adverse events were also examined. The median cumulative CTV The 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.

Hyaluronic acid gel injection in rectovaginal septum reduced incidence of rectal bleeding in brachytherapy for gynecological malignancies

The purpose of this study was to report our initial clinical results of hyaluronic acid gel injection (HGI) in the rectovaginal septum (RVS) to reduce the incidence of rectal bleeding in vaginal brachytherapy for gynecologic malignancies. Since 2008, CT based image-guided adaptive brachytherapy (IGABT) was initiated, and since 2015, HGI in the RVS was introduced in our institution. Vaginal cylinder with or without tandem or additional interstitial needles were applied for patients with gynecologic malignancies. Rectum dosimetric parameters and incidence of late rectum bleeding were compared between patients with and without HGI in the RVS. Between May 2008 and October 2017, 83 patients with gynecologic malignancies were treated with IGABT involving vaginal cylinder. Eleven patients who were treated for palliative intention were excluded, and 72 patients were subjected to the analysis. Of the total 72 patients 46 were with uterine cervical cancer, 19 uterine corpus cancer, five vaginal cancer, one vulvar cancer, and one ovarian cancer. Fifteen and 57 patients were irradiated with and without HGI in the RVS, respectively. With a median follow-up period of 57.7 (4.7-123.1) months, 30 (41.7%) patients suffered from radiation-related rectal bleeding. Patients with HGI in the RVS had a statistically significant lower incidence of rectal bleeding compared with those without it (13.3% vs. 49.1%, p = 0.01). HGI in the RVS reduced the incidence of late rectal bleeding for patients with gynecologic malignancies treated by vaginal cylinder and was not associated with HGI-procedure-related adverse events.

Configuration analysis of the injection position and shape of the gel spacer in gynecologic brachytherapy

In this single-institution retrospective study, configuration analysis was performed to determine the optimal location and volume of hyaluronic acid gel spacer injection into the rectovaginal or vesicovaginal septum for effective dose reduction (DR) to the organs at risk (OARs), the rectum and bladder. 70 and 50 intracavitary brachytherapy treatment plans used only vaginal cylinders with gel spacers for the rectal and bladder sides, respectively, whereas 28 did not use spacers. Correlation analysis was performed between the geometrical parameters and injection position of the gel spacers and the 2-cm A higher DR was predicted for hyaluronic acid gel spacer injection within ±5 mm and ±2.5 mm in the lateral-medial direction from the midpoint on the rectal and bladder sides, and ±10 mm in the cranial-caudal direction from the midpoint on the rectal side. There were correlations between 2-cm A gel spacer volume of ∼10 cm

Salvage image-guided freehand interstitial brachytherapy for pelvic sidewall recurrence after hysterectomy for uterine malignancies

Pelvic sidewall recurrence after hysterectomy for uterine malignances has a poor prognosis, and the salvage therapy for this type of recurrence is still challenging. The purpose of this study was to investigate the efficacy of freehand high-dose-rate interstitial brachytherapy (HDR-ISBT) through the perineum using transrectal ultrasonography for this disease. We retrospectively evaluated 42 patients with pelvic sidewall recurrence after hysterectomy for uterine cervical and endometrial cancers. We investigated patients' characteristics, the 2-year local control and survival rates, and late adverse events of the rectum and bladder. The 2-year overall survival, local control, and progression-free survival rates were 73.7% (95% confidence interval [CI], 60.8-89.3%), 69.4% (95% CI, 55.4-80.1%), and 37.3% (95% CI, 24.6-56.5%), respectively. In Cox multivariate analysis, tumor size at recurrence (<45 mm vs. ≥45 mm) (p = 0.04) and disease-free periods after hysterectomy (<10 months vs. ≥10 months) (p < 0.01) were significant prognostic factors for overall survival. Lymph node metastasis at recurrence (p < 0.01) was also a significant prognostic factor for progression-free survival. Three patients experienced Grade 3-4 late proctitis (7%). Transperineal freehand salvage HDR-ISBT using transrectal ultrasonography was demonstrated to be a curative treatment option for patients with pelvic sidewall recurrence following hysterectomy. Based on the findings of this study, we emphasize the importance of HDR-ISBT for pelvic sidewall recurrence.

Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial

Abstract Objective This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer. Methods Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30–30.6 Gy in 15–17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50–50.4 Gy in 25–28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be &amp;lt;10%. Results Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8–86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3–80.3 Gy) and bladder D2cc was 69.8 Gy (38.9–84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036). Conclusion The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial.

An Asian multi-national multi-institutional retrospective study comparing intracavitary versus the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical carcinoma

Abstract This study is an international multi-institutional retrospective study comparing the clinical outcomes between intracavitary brachytherapy (ICBT) and the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients treated with definitive radiation therapy. Locally advanced cervical cancer, the initial size of which is larger than 4 cm and treated by concurrent chemoradiotherapy and image-guided adaptive brachytherapy, were eligible for this retrospective study. Patients who received HBT at least once were included in the HBT group, and patients who received only ICBT were included in the ICBT group. Anonymized data from 469 patients from 13 institutions in Japan, one from Korea and one from Thailand, were analyzed. Two hundred eighty and 189 patients were included in the ICBT group and the HBT group, respectively. Patients in the HBT group had more advanced stage, non-Scc histopathology, a higher rate of uterine body involvement, larger tumor at diagnosis, larger tumor before brachytherapy and a lower tumor reduction ratio. With a median follow-up of 51.3 months (2.1–139.9 months), 4-y local control (LC), progression-free survival (PFS) and overall survival (OS) for the entire patient population were 88.2%, 64.2% and 83%, respectively. The HBT group received a higher HR-CTV D90 than that of the ICBT group (68.8 Gy vs 65.6 Gy, P = 0.001). In multivariate analysis, the non-Scc histological subtype, HR-CTV D95 ≤ 60 Gy, reduction ratio ≤ 29% and total treatment time (TTT) ≥ 9 weeks were identified as the independent adverse prognostic factors for LC. Regarding LC, no difference was found between ICBT and HBT (4-y LC 89.3% vs 86.8%, P = 0.314). After adjustment for confounding factors by propensity score matching, no advantage of applying HBT was demonstrated regarding LC, PFS, or OS. Despite the fact that HBT patients had more adverse clinical factors than ICBT patients, HBT delivered a higher dose to HR-CTV and resulted in comparable LC.

Safe dose escalation and reduction of the fraction number of uterine cervical brachytherapy using a gel spacer in the rectovaginal and vesicouterine septum: A planning study

To evaluate the possibility of dose escalation and reduction of fraction number in cervical brachytherapy using a gel spacer. Twenty patients with uterine cervical cancer treated with image-guided adaptive brachytherapy (IGABT) were selected. Hyaluronic acid gel injection (HGI) was performed in the rectovaginal and vesicouterine septum for 10 patients. The other ten patients were not with HGI. Both groups were treated with IGABT involving tandem/ovoid or cylindrical applicators along with additional interstitial needles. Dose distributions approved by radiation oncologists were retrospectively analyzed, and a dose summation of 45 Gy/25 of external beam radiation therapy and IGABT was performed. Dose constraints for D The median CTV In the HGI group, adequate dose delivery to CTV

Asian Gynecological Brachytherapy Registry in Cervical Cancer

Gynecological cancer poses as significant public health issue, especially in Asian countries, where it is a leading cause of cancer-related deaths among women. Cervical cancer accounts for around 311,000 deaths annually, with over 85% occurring in low- and middle-income nations, primarily in Asia. Factors contributing to this burden include limited access to preventive care, inadequate screening, high rates of human papillomavirus infection, and cultural barriers that delay medical attention. For patients with advanced cervical cancer, the standard treatment involves external beam radiation therapy along with chemotherapy followed by internal radiation, known as Brachytherapy. This technique uses unique set of devices placed internally at the tumor sitegiving localized radiation to the residual tumor tissue. While advanced brachytherapy techniques have been developed and practiced in Europe and American countries yielding excellent clinical outcomes, there is insufficient data on the use and results of such advanced brachytherapy techniques in Asian populations, leading to a lack of standardized practices. To address these issues, the Asian Gynecological Brachytherapy Registry (ABGR) has been established as a collaborative platform for data collection and analysis on the use of Brachytherapy techniques. This registry aims to consolidate information from various healthcare settings across Asia, enhancing understanding of cervical cancer's epidemiology, evaluating treatment effectiveness, and identifying areas for improvement in patient care.