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.

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 <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.

Optimal Number of Needle Applicators Inserted in Combined Intracavitary and Interstitial Brachytherapy for Cervical Cancer.

BACKGROUND/AIM: Combined intracavitary and interstitial brachytherapy (IC/IS-BT) is an effective treatment for extensive and bulky cervical cancer. However, the optimum number of interstitial needle applicators ("needles") inserted in IC/IS-BT can be difficult to determine. To examine the number of needles required for adequate dose coverage of cervical tumors, we retrospectively analyzed IC/IS-BT plans. PATIENTS AND METHODS: IC/IS-BT plans for cervical cancer patients treated from January 2014 to January 2021 were analyzed. All tumors were controlled locally at the time of analysis (August 2022). The relationship between the number of needles and several volumetric parameters of high-risk clinical target volume (CTVHR) were analyzed, including maximum diameter, maximum cross-sectional area, and the volume of CTVHR Spearman's rank correlation coefficients (r) were used to evaluate correlations. RESULTS: Eighty-two plans in 32 patients were analyzed. The median maximum cross-sectional area and volume of CTVHR were 18.9 (12.3-42.5) cm2 and 53.8 (30.1-152.2) cm3, respectively. The mean D90% and D98% of CTVHR at each BT session were 7.0±0.8 Gy and 5.9±0.8 Gy, respectively. There was a positive correlation between the number of needles and the maximum cross-sectional area of CTVHR (r=0.53). The average numbers of needles were 1.3, 1.9, 2.2, 3.1, and 4.0 when the maximum cross-sectional area of CTVHR were ≤15 cm2, 15-20 cm2, 20-25 cm2, 25-30 cm2, and >30 cm2, respectively. CONCLUSION: The optimal number of needles can be determined from the maximum cross-sectional area of CTVHR.

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

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.

Individualized and inverse optimized needle configuration for combined intracavitary-interstitial brachytherapy in locally advanced cervical cancer.

OBJECTIVES: The aim of this study is to address the limitation of combined intracavitary-interstitial (IC/IS) brachytherapy (BT) in locally advanced cervical cancer using standardized applicators and to determine the optimal dose distribution in patients with challenging tumors, innovative methods of customizing and optimizing the IS needle configuration for combined IC/IS BT are proposed and investigated. MATERIALS AND METHODS: A software module that could customize the IS needle configuration and subsequently generate the digital model of guiding template for three-dimensional printing was developed and integrated into our in-house treatment planning system for BT. The inverse optimization method based on the technique of mixed-integer linear programming was introduced to determine the needle tracks out of a candidate pool and dwell times at corresponding locations to best meet dose objectives. A treatment planning study was conducted to evaluate the feasibility and performance of the proposed methods. RESULTS: The workflow for combined IC/IS BT with customized and inverse optimized IS needle configuration was presented. Dosimetric results of the treatment planning study showed that sufficient target coverage could be obtained with the customized IS needle configuration for challenging cases. The proposed dose-based optimization method for IS needle configuration was feasible and effective. Improved target coverage and organ-at-risk sparing were achieved using the inverse planning method. CONCLUSIONS: Using the proposed methods of customizing and optimizing the IS needle configuration, the limitation in the standardized design of combined IC/IS applicators can be addressed, and sufficient target coverage is obtained in cervical cancer patients with unfavorable tumor topography and/or extra lateral expansion.

Combined intracavitary and interstitial brachytherapy of cervical cancer using the novel hybrid applicator Venezia: Clinical feasibility and initial results.

PURPOSE: To report on first-in-human experience and the initial clinical results using the hybrid applicator Venezia (Elekta, Sweden) in the treatment of patients with locally advanced cervical cancer. MATERIAL AND METHODS: Between March, 2017, and February, 2018, a total of 40 fractions were performed on patients undergoing definitive chemoradiation and brachytherapy (BT) for cervical cancer. A plan comparison was conducted evaluating the hybrid applicator with the clinically used intracavitary and interstitial (IC/IS) BT against a standard plan prescribed to Point A and a manually optimized plan using only intracavitary (IC) BT. Overall 80 treatment plans were retrospectively generated. RESULTS: The clinical use of the hybrid applicator system proved to be feasible in all 40 treatment fractions. The applicator consists of the IC tandem and two lunar-shaped ovoids forming a ring that serves as a template for defined parallel and oblique (12°) needle insertion. MRI preplanning was performed the day before the implant. One to six needles were placed per fraction, and overall a total of 66 needles were used. No complications such as bleeding or organ penetration occurred due to needle placement. Significant differences in IC/IS, Point A, and IC plans were derived for dose application to the target volume; D90 high-risk clinical target volume was 90.7 vs. 88.1 vs. 80.8 Gy (p = 0.008). Likewise, sparing of organs at risk differed significantly for bladder D2cc 79.4 vs. 91.8 vs. 79.2 Gy (p = 0.03) and rectum D2cc 58.7 vs. 67.3 vs. 62.5 Gy (p = 0.03). CONCLUSION: The clinical application of the Venezia applicator is feasible and allows significantly improved dose coverage while at the same time sufficiently sparing organs at risk.