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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.

Purpose Prostate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size. Methods and Materials Between 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950 cGy × 4 fractions, 1200 cGy × 2 fractions, 1350 cGy × 2 fractions, 1900 cGy × 1 fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0 ng/mL above the prior nadir with a subsequent return to the nadir. Results The median follow-up period was 3.7 years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0 ng/mL, respectively. The 3-year rate of PSA bounce >0.2 ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively ( P =.002). The hazard ratio for bounce >0.2 ng/mL for patients receiving a single fraction of 1900 cGy compared with those receiving treatment in multiple fractions was 1.786 ( P =.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2 ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels ( P =.025). Conclusions The incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures.

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

5 Background: We present a large retrospective analysis comparing 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. 545 (20.3%) received HDR and 2138 (79.7%) EBRT. 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). All EBRT patients underwent 3D image guidance via an off-line adaptive process. Treatment was directed to prostate only (n=780) or prostate and seminal vesicles (n=1351). No nodal therapy was given. Target volume for HDR patients included the prostate with no expansion. Acute and chronic gastrointestinal (GI) toxicity was defined as occurring ≤ 6 and > 6 months, respectively, after radiotherapy and was graded per CTCAE version 3.0. Toxicity variables were analyzed with χ2 test. Results: Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 69.1% of EBRT patients received IMRT with the remainder treated using 3D conformal technique. 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 vs. EBRT, respectively. For the 1478 EBRT patients treated with IMRT, acute and chronic rates of any grade ≥ 2GI toxicity were 4.2% and 5.6%, respectively, compared to 1.5% (p=0.002) and 2.4% (p=0.002), respectively, for HDR patients. Conclusions: In appropriately selected patients with localized prostate cancer undergoing definitive radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing acute and chronic rectal toxicity.

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 cm 3 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 192 Ir 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 cm 3 . 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.

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.

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.