21 Gy single fraction prostate HDR brachytherapy: 5-year results of a single institution prospective pilot study.

PURPOSE: To present the outcome and toxicity results of a prospective trial of 21 Gy single fraction high-dose-rate (HDR) brachytherapy for men with low- or intermediate-risk prostate cancer. METHODS AND MATERIALS: Patients were treated according to an IRB-approved prospective study of single fraction HDR brachytherapy. Eligible patients had low- or intermediate-risk prostate cancer with tumor stage ≤ T2b, PSA ≤ 15, and Gleason score ≤ 7. Patients underwent trans-rectal ultrasound-guided trans-perineal implant of the prostate followed by single fraction HDR brachytherapy to a dose of 21 Gy. The primary endpoint was grade ≥ 2 urinary/GI toxicity rates. RESULTS: Twenty-six patients were enrolled with a median follow up of 5.1 years and median age of 64 years. 88.5% of patients had T1 disease, 15.4% had Gleason score 6 (84.6% Gleason 7), and median pre-treatment PSA was 5.0 ng/mL. Acute and chronic grade ≥ 2 urinary toxicity rates were 38.5% and 38.5%, respectively. There were no grade ≥ 2 acute or chronic GI toxicities. Six (23.1%) patients experienced biochemical failure, six (23.1%) patients experienced radiographic local failure, and five (19.2%) patients had biopsy-proven local failure. No patients developed regional lymph node recurrence or distant metastasis. 5-year overall survival and cause-specific survival were 96.2% and 100%, respectively. CONCLUSIONS: 21 Gy single fraction HDR brachytherapy was associated with modestly higher-than-anticipated chronic urinary toxicity, as well as high biochemical and local failure rates. The results from this prospective pilot study do not support the use of this regimen in standard clinical practice.

Normal Tissue Integral Dose as a Result of Prostate Radiation Therapy: A Quantitative Comparison Between High-Dose-Rate Brachytherapy and Modern External Beam Radiation Therapy Techniques.

Purpose: Quantification of integral radiation dose delivered during treatment for prostate cancer is lacking. We performed a comparative quantification of dose to nontarget body tissues delivered via 4 common radiation techniques: conventional volumetric modulated arc therapy, stereotactic body radiation therapy, pencil-beam scanning proton therapy, and high-dose-rate brachytherapy. Methods and Materials: Plans for each radiation technique were generated for 10 patients with typical anatomy. For brachytherapy plans, virtual needles were placed to achieve standard dosimetry. Standard planning target volume margins or robustness margins were applied as appropriate. A "normal tissue" structure (entire computed tomography simulation volume minus planning target volume) was generated for integral dose computation. Dose-volume histogram parameters for targets and normal structures were tabulated. Normal tissue integral dose was calculated by multiplying normal tissue volume by mean dose. Results: Normal tissue integral dose was lowest for brachytherapy. Pencil-beam scanning protons, stereotactic body radiation therapy, and brachytherapy resulted in 17%, 57%, and 91% absolute reductions compared with standard volumetric modulated arc therapy, respectively. Mean nontarget tissues receiving 25%, 50%, and 75% of the prescription dose were reduced by 85%, 76%, and 83% for brachytherapy relative to volumetric modulated arc therapy, by 79%, 64%, and 74% relative to stereotactic body radiation therapy, and 73%, 60%, and 81% relative to proton therapy. All reductions observed using brachytherapy were statistically significant. Conclusions: High-dose-rate brachytherapy is an effective technique for reducing dose to nontarget body tissues relative to volumetric modulated arc therapy, stereotactic body radiation therapy, and pencil-beam scanning proton therapy.

Rates of rectal toxicity in patients treated with high dose rate brachytherapy as monotherapy compared to dose-escalated external beam radiation therapy for localized prostate cancer.

BACKGROUND: Using a prospectively collected institutional database, we compared rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer. METHODS: 2683 patients treated with HDR or EBRT between 1994 and 2017 were included. HDR fractionation was 38 Gy/4 fractions (n = 321), 24 Gy/2 (n = 96), or 27 Gy/2 (n = 128). EBRT patients received a median dose of 75.6 Gy in 1.8 Gy fractions [range 70.2-82.8 Gy], using either 3D conformal or intensity modulated radiotherapy (IMRT). EBRT patients underwent 3D image guidance via an off-line adaptive process. RESULTS: Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 545 patients (20.3%) received HDR brachytherapy and 2138 (79.7%) EBRT. 69.1% of EBRT patients received IMRT. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥2 diarrhea (0.7% vs. 4.5%, p < 0.001), rectal pain/tenesmus (0.6% vs. 7.9%, p < 0.001), and rectal bleeding (0% vs. 1.6%, p = 0.001). Rates of chronic grade ≥2 rectal bleeding (1.3% vs. 8.7%, p < 0.001) and radiation proctitis (0.9% vs. 3.3%, p = 0.001) favored HDR over EBRT. Rates of any chronic rectal toxicity grade ≥2 were 2.4% vs. 10.5% (p < 0.001) for HDR versus EBRT, respectively. In those treated with IMRT, acute and chronic rates of any grade ≥2 GI toxicity were significantly reduced but remained significantly greater than those treated with HDR. CONCLUSIONS: In appropriately selected patients with localized prostate cancer undergoing radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing rectal toxicity.

Five-Year Outcomes of a Single-Institution Prospective Trial of 19-Gy Single-Fraction High-Dose-Rate Brachytherapy for Low- and Intermediate-Risk Prostate Cancer.

PURPOSE: To update outcome and toxicity results of a prospective trial of 19-Gy single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: Patients were treated on a prospective study of single-fraction HDR brachytherapy. All patients had low- or intermediate-risk prostate cancer. Patients with prostate volumes >50 cm3, taking alpha-blockers for urinary symptoms, or with baseline American Urologic Association symptom scores >12 were ineligible. Patients underwent transrectal ultrasound-guided interstitial implant of the prostate followed by single-fraction HDR brachytherapy to a prescription dose of 19 Gy. RESULTS: Sixty-eight patients were enrolled with a median follow-up of 3.9 years. Median age was 62 years. Median gland volume at the time of treatment was 35 cm3, 92.6% of patients had T1 disease, 63.2% had a Gleason score of 6, and median pretreatment prostate-specific antigen was 5.0 ng/mL. Chronic grade 2 genitourinary toxicity was 14.7%. No grade 3 urinary toxicity occurred. A single patient experienced grade 2+ rectal toxicity (grade 3 diarrhea) that was transient and resolved with medical management. The 5-year estimated disease-free survival was 77.2% with no significant difference between low- and intermediate-risk patients. A single patient developed distant metastases during the follow-up period. Biopsy-proven local failure at 5 years was 18.8%, occurring at a median interval of 4.0 years posttreatment. No deaths occurred during follow-up. CONCLUSIONS: With extended follow-up, toxicity rates after single-fraction 19-Gy HDR brachytherapy remain low. Higher-than-expected rates of biochemical and local failure, however, raise concerns regarding the adequacy of this dose. Additional investigation to define the optimal single-fraction HDR brachytherapy dose is warranted, and single-fraction treatment currently should not be offered outside the context of a clinical trial.

Favorable Preliminary Outcomes for Men With Low- and Intermediate-risk Prostate Cancer Treated With 19-Gy Single-fraction High-dose-rate Brachytherapy.

PURPOSE: To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage ≤T2a, prostate-specific antigen level ≤15 ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50 cm3 and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using 192Ir to a dose of 19 Gy prescribed to the prostate, with no additional margin applied. RESULTS: Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9 years (range 0.3-5.2). The median age was 61.4 years. The median gland volume at treatment was 34.8 cm3. Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1 ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%. CONCLUSIONS: Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates.

Review of advanced catheter technologies in radiation oncology brachytherapy procedures.

The development of new catheter and applicator technologies in recent years has significantly improved treatment accuracy, efficiency, and outcomes in brachytherapy. In this paper, we review these advances, focusing on the performance of catheter imaging and reconstruction techniques in brachytherapy procedures using magnetic resonance images and electromagnetic tracking. The accuracy of catheter reconstruction, imaging artifacts, and other notable properties of plastic and titanium applicators in gynecologic treatments are reviewed. The accuracy, noise performance, and limitations of electromagnetic tracking for catheter reconstruction are discussed. Several newly developed applicators for accelerated partial breast irradiation and gynecologic treatments are also reviewed. New hypofractionated high dose rate treatment schemes in prostate cancer and accelerated partial breast irradiation are presented.

Real-time catheter tracking for high-dose-rate prostate brachytherapy using an electromagnetic 3D-guidance device: a preliminary performance study.

PURPOSE: In order to increase the accuracy and speed of catheter reconstruction in a high-dose-rate (HDR) prostate implant procedure, an automatic tracking system has been developed using an electromagnetic (EM) device (trakSTAR, Ascension Technology, VT). The performance of the system, including the accuracy and noise level with various tracking parameters and conditions, were investigated. METHODS: A direct current (dc) EM transmitter (midrange model) and a sensor with diameter of 1.3 mm (Model 130) were used in the trakSTAR system for tracking catheter position during HDR prostate brachytherapy. Localization accuracy was assessed under both static and dynamic analyses conditions. For the static analysis, a calibration phantom was used to investigate error dependency on operating room (OR) table height (bottom vs midposition vs top), sensor position (distal tip of catheter vs connector end of catheter), direction [left-right (LR) vs anterior-posterior (AP) vs superior-inferior (SI)], sampling frequency (40 vs 80 vs 120 Hz), and interference from OR equipment (present vs absent). The mean and standard deviation of the localization offset in each direction and the corresponding error vectors were calculated. For dynamic analysis, the paths of five straight catheters were tracked to study the effects of directions, sampling frequency, and interference of EM field. Statistical analysis was conducted to compare the results in different configurations. RESULTS: When interference was present in the static analysis, the error vectors were significantly higher at the top table position (3.3 ± 1.3 vs 1.8 ± 0.9 mm at bottom and 1.7 ± 1.0 mm at middle, p < 0.001), at catheter end position (3.1 ± 1.1 vs 1.4 ± 0.7 mm at the tip position, p < 0.001), and at 40 Hz sampling frequency (2.6 ± 1.1 vs 2.4 ± 1.5 mm at 80 Hz and 1.8 ± 1.1 at 160 Hz, p < 0.001). So did the mean offset errors in the LR direction (-1.7 ± 1.4 vs 0.4 ± 0.5 mm in AP and 0.8 ± 0.8 mm in SI directions, p < 0.001). The error vectors were significantly higher with surrounding interference (2.2 ± 1.3 mm) vs without interference (1.0 ± 0.7 mm, p < 0.001). An accuracy of 1.6 ± 0.2 mm can be reached when using optimum configuration (160 Hz at middle table position). When interference was present in the dynamic tracking, the mean tracking errors in LR direction (1.4 ± 0.5 mm) was significantly higher than that in AP direction (0.3 ± 0.2 mm, p < 0.001). So did the mean vector errors at 40 Hz (2.1 ± 0.2 mm vs 1.3 ± 0.2 mm at 80 Hz and 0.9 ± 0.2 mm at 160 Hz, p < 0.05). However, when interference was absent, they were comparable in the both directions and at all sampling frequencies. An accuracy of 0.9 ± 0.2 mm was obtained for the dynamic tracking when using optimum configuration. CONCLUSIONS: The performance of an EM tracking system depends highly on the system configuration and surrounding environment. The accuracy of EM tracking for catheter reconstruction in a prostate HDR brachytherapy procedure can be improved by reducing interference from surrounding equipment, decreasing distance from transmitter to tracking area, and choosing appropriated sampling frequency. A calibration scheme is needed to further reduce the tracking error when the interference is high.

Four-year results using balloon-based brachytherapy to deliver accelerated partial breast irradiation with a 2-day dose fractionation schedule.

PURPOSE: We present 4-year results from a Phase I/II trial using balloon-based brachytherapy to deliver accelerated partial breast irradiation in 2 days. MATERIALS/METHODS: Forty-five patients received breast-conserving surgery followed by adjuvant radiation therapy using a balloon-based brachytherapy applicator delivering 2800 cGy in four fractions over 2 days. Outcomes analyzed include toxicities scored using the NCI Common Toxicity Criteria v3.0 scale, ipsilateral breast tumor recurrence, regional nodal failure, distant metastasis, disease-free survival, cause-specific survival, and overall survival. RESULTS: Median age was 66 years (range, 48-83 years) and median tumor size was 0.6 cm (range, 0.2-2.3 cm). Five percent of patients were node positive (n=2), whereas 73% was estrogen receptor positive (n=33). Median followup was 3.7 years (2.4-7.0 years) with greater than 2 years of followup for all patients. Only Grades 1 and 2 chronic toxicities were noted with fat necrosis (18%) and asymptomatic seromas (42%) being the most common toxicities. Seven percent of patients developed ipsilateral rib fractures (n=3), although this was not statistically associated with maximum rib dose (p=0.31). Ninety-eight percent of patients had a good or excellent radiation-related cosmetic outcome at the time of last followup. There were no ipsilateral breast tumor recurrences or regional nodal failures; however, 2 patients developed distant metastases. Four-year actuarial disease-free survival, cause-specific survival, and overall survival were 96%, 100%, and 93%, respectively. CONCLUSIONS: Treatment of early-stage breast cancer patients with breast-conserving therapy using a 2-day radiation dose schedule resulted in acceptable chronic toxicity and similar clinical outcomes as standard 5-day fractionation.

High-dose-rate brachytherapy as monotherapy delivered in two fractions within one day for favorable/intermediate-risk prostate cancer: preliminary toxicity data.

PURPOSE: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. METHODS AND MATERIALS: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. RESULTS: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. CONCLUSIONS: Favorable-risk prostate cancer patients treated with a single implant HDR-BT to 24-27 Gy in two fractions within 1 day have excellent tolerance with minimal acute and chronic toxicity. Longer follow-up is needed to confirm these encouraging early results.