Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial.

Importance: Hypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT. Objective: To evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT. Design, Setting, and Participants: This randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to µg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality. Main Outcomes and Measures: For the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%. Results: Of the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% (P < .001). The mean (SD) reduction was 85.0% (20.9%). For the secondary outcome, 4 of 136 patients (2.9%) in the spacer group and 9 of 65 patients (13.8%) in the control group experienced acute grade 2 or higher GI toxic effects (difference, -10.9%; 95% 1-sided upper confidence limit, -3.5; P = .01). Conclusions and Relevance: The trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT. Trial Registration: ClinicalTrials.gov Identifier: NCT04189913.

HDR Brachytherapy Planning using Active Needles - Preliminary Investigation on Dose Planning.

In this study we present a new approach to plan a high-dose-rate (HDR) prostate brachytherapy (BT) using active needles recently developed by our group. The active needles realize bi-directional bending inside the tissue, and thereby more compliant with the patient's anatomy compared with conventional straight needles. A computational method is presented to first generate a needle arrangement configuration based on the patient's prostate anatomy. The needle arrangement is generated to cover the prostate volume, providing accessible channels for the radiation source during a HDR BT. The needle arrangement configuration avoids healthy organs and prevents needle collision inside the body. Then a treatment plan is proposed to ensure sufficient prescribed dosage to the whole prostate gland. The method is applied to a prostate model reconstructed from an anonymized patient to show the feasibility of this method. Finally, the active needle's capability to generate the required bending is shown. We have shown that our method is able to automatically generate needle arrangement configuration using active needles, and plan for a treatment that meets the dose objectives while using fewer needles (about 20% of conventional straight needles) than the conventional HDR BT performed by straight needles.

Steering a Tendon-Driven Needle in High-Dose-Rate Prostate Brachytherapy for Patients with Pubic Arch Interference.

High-dose-rate brachytherapy (HDR BT) is a radiation therapy that places radioactive sources at cancerous tissue using needles. HDR BT offers better dose conformality and sparing of clinical structures, lower operator dependency, and fewer acute irritative symptoms compared to the other form of BT (low-dose-rate (LDR)). However, use of HDR BT is limited for patients with pubic arch interference, where the transperineal path to the prostate is blocked. This study aims to introduce a tendon-driven needle that can bend inside tissue to reach desired positions inside prostate. Initial experiments in a phantom tissue showed the feasibility of the needle to get around the pubic arch for placement at hard-to-reach target positions.

Placement of SpaceOAR hydrogel spacer for prostate cancer patients treated with iodine-125 low-dose-rate brachytherapy.

OBJECTIVES: The aim of the present study was to report on our early experience with hydrogel spacer (SpaceOAR) placement in combination with iodine-125 low-dose-rate brachytherapy for prostate cancer. METHODS: From April 2018, SpaceOAR hydrogel spacer was placed in 100 consecutive patients undergoing iodine-125 low-dose-rate brachytherapy. Complications and the status of the placement were evaluated. Deformation of the prostate by the spacer was examined measuring prostate diameters and evaluating the change from preoperative status. The position of the prostate was similarly examined by evaluating the change in distance between the pubic symphysis and the prostate. Post-plan dosimetric data were compared with 200 patients treated without a spacer. RESULTS: No complications were found during either the intraoperative or perioperative periods. The mean displacement distance of 11.64 mm was created, the mean value before spacer placement was 0.28 mm (P < 0.0001). The change of the prostate diameters showed a positive increase in all directions, with no significant negative change in any one direction. Regarding the change in distance between pubic symphysis and the prostate, no significant shortening trend was observed between the two groups (P = 0.14). Whereas the dosimetric parameters showed means of 0.001 and 0.026 cc for RV150 and RV100 in the spacer group, they were 0.025 and 0.318 cc, respectively, in the non-spacer group, showing a significant decrease in both parameters (P < 0.001). CONCLUSIONS: Prostate deformation secondary to hydrogel placement might adversely affect dosimetric parameters in patients undergoing low-dose-rate brachytherapy. However, a significant reduction in the rectal dose can be adopted without adversely affecting the other parameters related to treatment outcome.

Transperineal interstitial permanent prostate brachytherapy for Japanese prostate cancer patients in Hawaii.

BACKGROUND: Our aim was to report clinical and biochemical outcomes of transperineal interstitial permanent prostate brachytherapy in the treatment of Japanese patients with clinically organ-confined prostate cancer in Hawaii. METHODS: Ninety-five Japanese patients underwent transperineal interstitial permanent prostate brachytherapy using either iodine-125 or palladium-103 for clinical T1c-T2b N0 M0 prostate cancer. These procedures were carried out between December 1998 and December 2002 at The Queen's Medical Center in Honolulu, Hawaii. Prostate-specific antigen measurements were collected from all patients at follow up. Biochemical failure was defined by three consecutive rises in prostate-specific antigen levels, based on the criteria of the American Society for Therapeutic Radiology and Oncology Consensus panel. RESULTS: The median patient age was 71 years (range, 46-87 years). Thirty-six patients were implanted with either iodine-125 or palladium-103 as monotherapy; 59 patients received moderate-dose external beam irradiation first, followed by a prostate brachytherapy boost. The median follow-up length, calculated from the day of implantation, was 801 days (range, 237-1421 days). During this follow-up period, The Kaplan-Meier estimate of freedom from biochemical failure in this series was 94%. No major complications were observed. CONCLUSIONS: Clinical and biochemical outcomes in the treatment of Japanese patients in Hawaii suffering from localized prostate cancer, using transperineal interstitial permanent prostate brachytherapy, with or without external beam irradiation, compared favorably to results in similarly treated patients in the general US population.

[PSA bounce phenomenon after transperineal interstitial permanent prostate brachytherapy for localized prostate cancer].

PURPOSE: We described the temporarily increase phenomenon in prostate-specific antigen level (PSA bounce) after transperineal interstitial permanent prostate brachytherapy (TIPPB) for localized prostate cancer. MATERIALS AND METHODS: From December 1998 to May 2003, 500 consecutive patients with localized prostate cancer were treated with TIPPB using iodine-125 or palladium-103. We examined 200 patients who have more than 2-year PSA follow-up. Median follow-up length was 1,069 days (range, 712-1,411 days). No patient received neoadjuvant or adjuvant hormone therapy. PSA determinations were performed every 3 months for the first 2 years after procedure, and every 6 months hereafter. PSA bounce was defined as an increase of 0.1 ng/ml or greater above the preceding PSA level after implant followed by a subsequent decrease below that level. The American Society for Therapeutic Radiology and Oncology (ASTRO) consensus panel criteria 1996 were used to define biochemical failure. RESULTS: PSA bounce was observed in 40% (80/200) of the cases receiving TIPPB. The median time to PSA bounce was 13 months from the day of implant. The median magnitude of the PSA bounce was 0.3 ng/ml from the pre-bounce level. Twelve cases demonstrated biochemical failure according to the ASTRO consensus guidelines of three consecutive rises in PSA. Ten of these subsequently showed a drop in PSA, consistent with biologic control of their disease. Two cases remain classified as apparent biochemical failures. CONCLUSIONS: A transient rise in the PSA following TIPPB, the so-called "bounce" is a common occurrence. The apparent PSA control of ten of twelve cases failing by the ASTRO criteria raises some concern. Further observation will be necessary to determine ways to discriminate these from true disease progression.