Hiroshi Igaki

Technical report on the first clinical use of a bioabsorbable PGA spacer in HDR brachytherapy for recurrent cervical cancer

Abstract In recurrent gynecologic malignancies following prior pelvic irradiation, definitive radiation therapy is often precluded by cumulative dose constraints to adjacent organs at risk (OARs), and patients may be left with only highly invasive surgical options such as total pelvic exenteration. While some institutions have explored displacement techniques such as artificial ascites or hyaluronic acid gel injection, these approaches are not widely adopted and frequently fail to ensure consistent and stable separation of OARs. We report the first clinical use of Neskeep®, a bioabsorbable polyglycolic acid (PGA) spacer, in high-dose-rate (HDR) brachytherapy for recurrent cervical cancer after prior pelvic radiation. A woman in her 40s with prior hysterectomy and HDR brachytherapy for cervical intraepithelial neoplasia grade III developed vaginal stump recurrence 4 years later. Laparoscopic placement of the PGA spacer was performed to achieve durable displacement of the small bowel, followed by eight fractions of HDR brachytherapy. Hyaluronic acid gel was also injected during each fraction to displace the bladder and rectum. The spacer maintained position and volume throughout treatment without complications. Dose–volume analysis showed a marked reduction in small bowel D₂cc (mean equivalent dose in 2 Gy fractions (EQD₂): 121.6 cGy) compared to the initial treatment (606.0 cGy), while the spacer itself received a mean D₂cc of 690.3 cGy. MRI confirmed complete response at 2 months, with no adverse events observed at that time point. The PGA spacer enabled safe, curative reirradiation in a case that would otherwise be unsuitable for further radiation therapy.

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.

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.

Evaluation of the dosimetric impact and safety of MucoUp as a spacer in gynecologic brachytherapy

Gynecologic brachytherapy (BT) is an essential component of definitive radiation therapy, but excessive radiation exposure to organs at risk (OARs) remains a major concern. MucoUp, a hyaluronic acid-based spacer, has been introduced to physically separate the high-risk clinical target volume (HR-CTV) from adjacent OARs. However, its clinical feasibility and dosimetric impact remain underexplored. This study aimed to evaluate the dosimetric impact and clinical feasibility of MucoUp in high-dose-rate (HDR) gynecologic BT. A retrospective analysis was conducted on 5 patients with gynecologic malignancies who underwent HDR BT with and without MucoUp injection. Dosimetric parameters, including HR-CTV D90 and OAR D2cc (bladder, rectum), were compared between sessions with and without MucoUp. Spacer volume retention was assessed using pre- and post-treatment CT scans. MucoUp injection resulted in a significant reduction in rectal D2cc (7.19 Gy vs. 6.73 Gy, p = 0.043), while maintaining HR-CTV dose coverage (D90: 8.82 Gy vs. 9.15 Gy, p = 0.043). A nonsignificant reduction in bladder D2cc was observed (7.51 Gy vs. 7.16 Gy, p = 0.34). Spacer volume retention remained stable throughout treatment. No procedural complications or acute toxicity were observed. This study suggests that MucoUp is a promising spacer for gynecologic BT, effectively reducing rectal dose while preserving HR-CTV coverage. Given its high stability and safety, MucoUp may serve as an alternative to existing spacer materials. Further large-scale and long-term studies are warranted to evaluate its impact on late toxicities.