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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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Shorter courses of accelerated partial-breast irradiation delivered as single-fraction intraoperative therapy are now offered as an alternative to 4 to 6 weeks of whole-breast irradiation after lumpectomy. However, this approach has potential shortcomings in patient selection and target volume definition and in dosimetric, radiobiological, and logistical issues. We designed a prospective, phase 2, multi-institution clinical trial to study 2- or 3-day accelerated partial breast irradiation delivered with brachytherapy applicators., Methods and Materials: This trial treats select breast cancers after breast-conserving surgery with brachytherapy applicators that deliver 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 1.5 cm beyond the surgical cavity. Eligible women were aged ≥45 years with unicentric invasive or in situ tumors ≤3.0 cm with positive estrogen or progesterone receptors and no metastasis to axillary nodes that have been excised with negative margins. Strict dosimetric parameters were required to be met before acceptance into the trial., Results: A group of 200 patients was prospectively enrolled and followed for a minimum of 6 months. Two- or 3-day brachytherapy was associated with low acute or subacute toxicity, 97.25% excellent or good cosmetic outcomes, and excellent local control in select breast cancers., Conclusions: Ultrashort breast brachytherapy is dosimetrically feasible and can be delivered with excellent short-term tolerance and low toxicity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: To report 6-year outcomes from a phase I/II trial using balloon-based brachytherapy to deliver APBI in 2 days., Methods: A total of 45 patients with early-stage breast cancer received adjuvant APBI in 2 days with high-dose rate (HDR) brachytherapy totaling 2800 cGy in 4 fractions (700 cGy BID) using a balloon-based applicator as part of a prospective phase I/II clinical trial. All patients had negative margins and skin spacing ≥8 mm. We evaluated toxicities (CTCAE v3) as well as ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), distant metastasis, disease-free survival, cause-specific survival, and overall survival., Results: Median age and tumor size were 66 years old (48 to 83) and 0.8 cm (0.2 to 2.3 cm), respectively. Four percent of patients were N1 (n=2) and 73% were estrogen receptor (ER) positive (n=32). Median follow-up was 6.2 years (2.4 to 8.0 y). Nearly all toxicities at 6 years were grade 1 to 2 except 1 instance of grade 3 telangiectasia (2%). Eleven percent (n=5) of patients had chronic asymptomatic fat necrosis whereas asymptomatic seromas were noted on mammogram in 13% of cases (n=6). Cosmesis at last follow-up was good or excellent in 91% of cases (n=40) and fair in 9% (n=4). Two of the previously reported rib fractures healed with conservative measures. There were no IBTR or RNF (6 y IBTR/RNF rate 0%); however, 2 patients experienced distant metastasis (4% at 6 y). The 6-year actuarial disease-free survival, cause-specific survival, and overall survival were 96%, 100%, and 93%, respectively., Conclusions: Hypofractionated 2-day APBI using brachytherapy resulted in excellent clinical outcomes with acceptable chronic toxicities.

Objectives: Limited long-term data exist regarding outcomes for patients treated with accelerated partial breast irradiation (APBI), particularly, when stratified by American Society for Radiation Oncology (ASTRO) Consensus Statement (CS) risk groups. The purpose of this analysis is to present 5- and 7-year outcomes following APBI based on CS groupings., Materials and Methods: A total of 690 patients with early-stage breast cancer underwent APBI from 1993 to 2012, receiving interstitial brachytherapy (n=195), balloon-based brachytherapy (n=290), or 3-dimensional conformal radiotherapy (n=205) at a single institution. Patients were stratified into suitable, cautionary, and unsuitable groups with 5-year outcomes analyzed. Seven-year outcomes were analyzed for a subset with follow-up of ≥2 years (n=625)., Results: Median follow-up was 6.7 years (range, 0.1 to 20.1 y). Patients assigned to cautionary and unsuitable categories were more likely to have high-grade tumors (21% to 25% vs. 9%, P=0.001), receive chemotherapy (15% to 38% vs. 6%, P<0.001), and have close/positive margins (9% to 11% vs. 0%, P<0.001). There was no difference in ipsilateral breast tumor recurrence at 5 or 7 years: 2.2%, 1.2%, 2.8% at 5 years (P=0.57), and 2.2%, 1.9%, 4.6% at 7 years (P=0.58) in the suitable, cautionary, and unsuitable groups, respectively. As compared with the suitable group, increased rates of distant metastases were noted for the unsuitable and cautionary groups at 5 years (P=0.04)., Conclusions: No differences in rates of ipsilateral breast tumor recurrence were seen at 5 or 7 years when stratified by ASTRO CS groupings. Modest increases in distant recurrence were noted in the cautionary and unsuitable groups. These findings suggest that the ASTRO CS groupings stratify more for systemic recurrence and may not appropriately select patients for whole versus partial breast irradiation.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: We report the outcomes associated with 3 high-dose-rate (HDR) brachytherapy regimens used as monotherapy for favorable-risk prostate cancer., Methods and Materials: Four hundred ninety-four patients with stage ≤T2b prostate cancer, Gleason score ≤7, and prostate-specific antigen levels ≤15 ng/mL underwent HDR brachytherapy as monotherapy. Of those, 319 received 38 Gy in 4 fractions, 79 received 24 Gy in 2 fractions, and 96 received 27 Gy in 2 fractions. Acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicities were defined as side effects occurring ≤6 and >6 months, respectively, after radiation therapy (RT) and were graded according to the Common Terminology Criteria for Adverse Events version 3.0. The time to toxicity was calculated from the date of RT completion. Variables were analyzed with χ(2) test. P values <.05 were considered significant., Results: The median overall follow-up time was 4 years (range, 5.5, 3.5, and 2.5 years for 38 Gy, 24 Gy, and 27 Gy, respectively, P<.001). Acute and chronic grade ≥2 GU and GI toxicity profiles were similar among groups. Acceptable rates of grade 2 GU toxicities were seen with overall acute/chronic frequency/urgency, dysuria, retention, incontinence, and hematuria rates of 14%/20%, 6%/7%, 7%/4%, 1.5%/2%, and 1.5%/7%, respectively. Minimal grade 3 and no grade 4 or 5 toxicities were seen. Grade 1, 2, and 3 chronic urethral stricture rates were 0.3%, 2%, and 1%, respectively. All GI toxicities were similar between groups, with overall rates of acute/chronic grade 2 diarrhea, rectal pain/tenesmus, rectal bleeding, and proctitis of 1%/1%, <1%/0.5%, 0%/2%, and <1%/1%, respectively. No grade 3, 4, or 5 toxicities were seen. All comparisons were similar for hormone-naïve patients. The median time to maximal GU/GI toxicity was similar between groups, ranging from 1 to 1.6 to 0.9 to 1.2 years, respectively. There were no differences in clinical outcomes between the 3 groups at 5 years., Conclusions: The acute and chronic toxicity profiles associated with these 3 HDR brachytherapy schedules were similar and were well tolerated. Acceptable grade 2, minimal grade 3, and no grade 4 or 5 toxicities were seen. This, combined with the fact that the clinical outcomes were similar, leads to the conclusion that all 3 regimens may be acceptable options for the management of low-risk to intermediate-risk prostate cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Brachytherapy-based APBI (bAPBI) shortens treatment duration and limits dose to normal tissue. While studies have demonstrated similar local control when comparing bAPBI and whole breast irradiation using intensity modulated radiotherapy (WBI-IMRT), comparison of late side effects is limited. Here, we report chronic toxicity profiles associated with these two treatment modalities., Methods: 1034 patients with early stage breast cancer were treated at a single institution; 489 received standard-fractionation WBI-IMRT between 2000 and 2013 and 545 received bAPBI (interstitial 40%, applicator-based 60%) between 1993 and 2013. Chronic toxicity was evaluated ≥6 months utilizing CTCAE version 3.0; cosmesis was evaluated using the Harvard scale., Results: Median follow-up was 4.6 years (range 0.1-13.4) for WBI-IMRT versus 6.7 years (range 0.1-20.1) for bAPBI (p < 0.001). Compared to WBI-IMRT, bAPBI was associated with higher rates of ≥grade 2 seroma formation (14.4% vs 2.9%, p < 0.001), telangiectasia (12.3% vs 2.1%, p = 0.002) and symptomatic fat necrosis (10.2% vs 3.6%, p < 0.001). Lower rates of hyperpigmentation were observed (5.8% vs 14.5%; p = 0.001). Infection rates were similar (3.3% vs 1.3%, p = 0.07). There was no difference between rates of fair (6.1% vs. 4.1%, p = 0.30) or poor (0.2% vs. 0.5%, p = NS) cosmesis. Mastectomy rates for local recurrence (3.1% for WBI-IMRT and 1.2% for bAPBI, p = 0.06), or for other reasons (0.8% and 0.6%, p = 0.60) were similar between groups., Conclusion: With 5-year follow-up, WBI-IMRT and bAPBI are associated with similar, acceptable rates of toxicity. These data further support the utilization of bAPBI as a modality to deliver adjuvant radiation in a safe and efficacious manner., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To develop a nomogram taking into account clinicopathologic features to predict locoregional recurrence (LRR) in patients treated with accelerated partial-breast irradiation (APBI) for early-stage breast cancer., Methods and Materials: A total of 2000 breasts (1990 women) were treated with APBI at William Beaumont Hospital (n=551) or on the American Society of Breast Surgeons MammoSite Registry Trial (n=1449). Techniques included multiplanar interstitial catheters (n=98), balloon-based brachytherapy (n=1689), and 3-dimensional conformal radiation therapy (n=213). Clinicopathologic variables were gathered prospectively. A nomogram was formulated utilizing the Cox proportional hazards regression model to predict for LRR. This was validated by generating a bias-corrected index and cross-validated with a concordance index., Results: Median follow-up was 5.5 years (range, 0.9-18.3 years). Of the 2000 cases, 435 were excluded because of missing data. Univariate analysis found that age <50 years, pre-/perimenopausal status, close/positive margins, estrogen receptor negativity, and high grade were associated with a higher frequency of LRR. These 5 independent covariates were used to create adjusted estimates, weighting each on a scale of 0-100. The total score is identified on a points scale to obtain the probability of an LRR over the study period. The model demonstrated good concordance for predicting LRR, with a concordance index of 0.641., Conclusions: The formulation of a practical, easy-to-use nomogram for calculating the risk of LRR in patients undergoing APBI will help guide the appropriate selection of patients for off-protocol utilization of APBI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To determine whether the American Society for Radiation Oncology (ASTRO) Consensus Statement (CS) recommendations for accelerated partial breast irradiation (APBI) are associated with significantly different outcomes in a pooled analysis from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite® Registry Trial., Methods and Materials: APBI was used to treat 2127 cases of early-stage breast cancer (WBH, n=678; ASBrS, n=1449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3-dimensional conformal radiation therapy, n=206), whereas all Registry Trial patients received balloon-based brachytherapy. Patients were divided according to the ASTRO CS into suitable (n=661, 36.5%), cautionary (n=850, 46.9%), and unsuitable (n=302, 16.7%) categories. Tumor characteristics and clinical outcomes were analyzed according to CS group., Results: The median age was 65 years (range, 32-94 years), and the median tumor size was 10.0 mm (range, 0-45 mm). The median follow-up time was 60.6 months. The WBH cohort had more node-positive disease (6.9% vs 2.6%, P<.01) and cautionary patients (49.5% vs 41.8%, P=.06). The 5-year actuarial ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the whole cohort were 2.8%, 0.6%, 1.6%. The rate of IBTR was not statistically higher between suitable (2.5%), cautionary (3.3%), or unsuitable (4.6%) patients (P=.20). The nonsignificant increase in IBTR for the cautionary and unsuitable categories was due to increased elsewhere failures and new primaries (P=.04), not tumor bed recurrence (P=.93)., Conclusions: Excellent outcomes after breast-conserving surgery and APBI were seen in our pooled analysis. The current ASTRO CS guidelines did not adequately differentiate patients at an increased risk of IBTR or tumor bed failure in this large patient cohort., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To report outcomes for ductal carcinoma in situ (DCIS) treated with breast-conserving therapy using accelerated partial breast irradiation (APBI)., Methods and Materials: From March 2001 to February 2009, 53 patients with Stage 0 breast cancer were treated with breast conserving surgery and adjuvant APBI. Median age was 62 years. All patients underwent excision with margins negative by ≥1 mm before adjuvant radiotherapy (RT). A total of 39 MammoSite brachytherapy (MS) patients and 14 three-dimensional conformal external beam RT (3DCRT) patients were treated to the lumpectomy bed alone with 34 Gy and 38.5 Gy, respectively. Of the DCIS cases, 94% were mammographically detected. All patients with calcifications had either specimen radiography or postsurgical mammography confirmation of clearance. Median tumor size was 6 mm, and median margin distance was 5 mm. There were no statistically significant differences according to APBI method for race/ethnicity, tumor detection method, tumor grade, estrogen receptor (ER) status, or use of tamoxifen (p = NS). Recurrence and survival were calculated using the Kaplan-Meier method. Cosmesis was scored by the Harvard criteria., Results: With a median follow-up of 3.6 years (range, 0.4-6.3 years), the overall and cause-specific survival rates were 98% and 100%, respectively. Three-year actuarial ipsilateral breast tumor recurrence was 2%. One failure was observed at the resection bed 11 months post-RT. No other elsewhere breast failures, regional recurrences, or distant metastases were noted. Cosmesis was excellent or good in 92.4% of cases, with no statistically significant differences according to the APBI method (92.3% with MammoSite and 92.8% with 3DCRT; p = 0.649)., Conclusions: APBI as part of breast-conserving therapy for pure DCIS was associated with excellent local control and survival rates, with the vast majority of patients having good to excellent cosmesis. This finding supports the recent analysis by the American Society of Breast Surgeons on a subset of DCIS patients treated efficaciously with APBI., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Initial Phase I/II results using balloon brachytherapy to deliver accelerated partial breast irradiation (APBI) in 2 days in patients with early-stage breast cancer are presented., Materials and Methods: Between March 2004 and August 2007, 45 patients received adjuvant radiation therapy after lumpectomy with balloon brachytherapy in a Phase I/II trial delivering 2800 cGy in four fractions of 700 cGy. Toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria for Adverse Events v3.0 scale and cosmesis was documented at >or=6 months., Results: The median age was 66 years (range, 48-83) and median skin spacing was 12 mm (range, 8-24). The median follow-up was 11.4 months (5.4-48 months) with 21 patients (47%) followed >or=1 year, 11 (24%) >or=2 years, and 7 (16%) >or=3 years. At <6 months (n = 45), Grade II toxicity rates were 9% radiation dermatitis, 13% breast pain, 2% edema, and 2% hyperpigmentation. Grade III breast pain was reported in 13% (n = 6). At >or=6 months (n = 43), Grade II toxicity rates were: 2% radiation dermatitis, 2% induration, and 2% hypopigmentation. Grade III breast pain was reported in 2%. Infection was 13% (n = 6) at <6 months and 5% (n = 2) at >or=6 months. Persistent seroma >or=6 months was 30% (n = 13). Fat necrosis developed in 4 cases (2 symptomatic). Rib fractures were seen in 4% (n = 2). Cosmesis was good/excellent in 96% of cases., Conclusions: Treatment with balloon brachytherapy using a 2-day dose schedule resulted acceptable rates of Grade II/III chronic toxicity rates and similar cosmetic results observed with a standard 5-day accelerated partial breast irradiation schedule., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to assess the cosmesis and toxicities in patients with early-stage breast carcinoma who received treatment with accelerated partial breast irradiation (APBI) using interstitial brachytherapy., Methods: From April 1993 to December 2001, 199 patients with Stage I-II breast carcinoma received breast-conserving therapy with APBI to the tumor bed alone through a low-dose-rate (LDR) or high-dose-rate (HDR) implant. A template guide was used. The LDR dose was 50 Gray (Gy) over 96 hours; the outpatient HDR implant delivered 32 Gy in 8-Gy or 34 Gy in 10-Gy twice-daily fractions. Cosmesis (Harvard criteria) and toxicities (Radiation Therapy Oncology Group guidelines) were assessed at < or = 6 months, 2 years, and 5 years., Results: The median follow up was 6.4 years. Breast pain, edema, erythema, and hyperpigmentation all diminished over time. Breast fibrosis and hypopigmentation increased until the 2-year mark and then stabilized. Fat necrosis and telangiectasia increased over time, with a fat necrosis rate of 11% at 5 years. Nearly all telangiectasias (34% at 5 yrs) were Grade 1 (< 2 mm). The remaining toxicities were Grade 1 at all follow-up intervals. Infections (11%) occurred predominantly within the first month after treatment. Good-to-excellent cosmetic outcomes were noted in 95-99% of patients over time; cosmetic results stabilized at 2 years with excellent results increased out to 5 years., Conclusions: APBI with interstitial brachytherapy resulted in mild chronic toxicities, the majority of which diminished or reached a plateau over time. Long-term cosmesis was good to excellent in 95-99% of patients and stabilized at 2 years.

Purpose: We report the first single-institutional dosimetric comparison of patients treated with three forms of accelerated partial breast irradiation: interstitial HDR brachytherapy, the MammoSite balloon apparatus, and 3D conformal external beam quadrant irradiation (3D-CRT)., Methods: A retrospective dosimetric comparison of interstitial HDR brachytherapy, MammoSite balloon brachytherapy, and 3D-CRT was performed. Thirty patients including 10 from each treatment technique were included for a dosimetric comparison of the dose received by the ipsilateral breast, PTV, heart, and ipsilateral lung. Interstitial patients were treated with 4 Gy in 8 fractions to 32 Gy, and the MammoSite patients were treated with 3.4 Gy in 10 fractions to 34 Gy. 3D-CRT patients were treated with 3.85 Gy in 10 fractions to 38.5 Gy using multiple isocentric beams. The CT images from simulation or implant evaluation were transferred into our 3D treatment planning software. The lumpectomy cavities were outlined for every patient, except the MammoSite patients, where the cavity was defined by the balloon edge. The PTV was constructed as a uniform expansion of 1.5 cm for all interstitial HDR patients, 1.0 cm for the MammoSite patients, and a 1.0 cm expansion in addition to the CTV expansion of 1.0 cm (n=2), and 1.5 cm (n=8) for the 3D-CRT patients. The CTV expansion for 3D-CRT and the PTV expansion for the brachytherapy patients were limited to the chest wall and skin. Normal structures including both ipsilateral lung and breast and heart for left-sided lesions were outlined. The lumpectomy cavity was subtracted from the PTV and normal breast tissue for evaluation. To evaluate dose to the ipsilateral breast and lung, PTV, and heart, a dose-volume histogram (DVH) analysis was performed. All histograms were normalized to the volume of the structure (i.e., expressed as percent volume)., Results: The average percentage of the breast receiving 100% and 50% of the prescribed dose (PD) was higher in the 3D-CRT group (24% and 48%, respectively) compared with the MammoSite (5% and 18%, respectively) and interstitial patients (10% and 26%, respectively). Improved coverage of the PTV was noted in the 3D-CRT plans compared with the MammoSite and interstitial HDR plans. With the interstitial HDR technique, 58% of the PTV received 100% of the PD compared with 76% with MammoSite and 100% with 3D-CRT techniques. The percentage of the PTV receiving 90% of the PD was 68%, 91%, and 100% for the interstitial HDR, MammoSite, and 3D-CRT patients, respectively. The ipsilateral lung V20 was slightly higher for 3D-CRT at 5% compared with 0% for both brachytherapy techniques., Conclusion: In those treated with 3D-CRT, coverage of the PTV was better with 3D-CRT but varied with the definition used. At the coverage at 90% of the PD, no difference was observed between 3D-CRT and MammoSite (which were both better than interstitial). 3D-CRT resulted in better coverage of the PTV compared with MammoSite or interstitial brachytherapy techniques. Better PTV coverage with 3D-CRT came at the cost of a higher integral dose to the remaining normal breast. Dosimetrically, the best partial breast irradiation technique appears to depend on the clinical situation. Of the brachytherapy techniques, MammoSite appears to be superior in PTV coverage. When comparing MammoSite vs. 3D-CRT PTV coverage at 90% of the PD, the difference was not significantly different.

Objective: To examine early and late toxicities, evaluate cosmetic results, and determine the need for reoperation or additional diagnostic procedures in patients treated with accelerated partial breast irradiation (APBI) delivered by way of an interstitial implant in breast-conserving therapy., Methods: A total of 199 patients with stage I or II breast cancer were managed with lumpectomy followed by radiation restricted to the tumor bed using an interstitial implant (APBI). Retrospective analyses were performed for early and late toxicities (infection, fat necrosis, breast pain, edema, erythema, fibrosis, pigmentation changes, and telangiectasias), need for reoperation or additional diagnostic procedures, cosmetic results, and local control. Patient selection criteria by the surgeon for referral to RT for APBI included age, tumor size, histology, nodal status, margin status, and absence of extensive intraductal component. Treatment was delivered with either a low-dose or high-dose rate implant. Median follow-up was 5.7 years, and 54% of the patients were followed-up for >7 years., Results: Infections developed in 22 of 199 (11%) patients: 7% early (1 month after implant removal). Five of the 22 patients (2% of all patients) required operative intervention for the infection, either incision and drainage or debridement. There was a statistically significant difference between infection rates with open (8.5%) versus closed (2.5%) cavity placement of the interstitial needles (P = 0.005). There was no statistically significant difference between low-dose rate (inpatient) and high-dose rate (outpatient) treatment (P = 0.207). Forty-five patients (23%) had an additional diagnostic procedure to evaluate a suspicious or uncertain finding on physical examination or mammogram. Fibrosis and fat necrosis were found in 26 of the 45 patients. The incidence of fat necrosis increased with time. More patients were found to have fat necrosis after 5 years. One patient had fat necrosis diagnosed at <6 months; 8 patients (4% of total) at >/=6 months to <2 years; 10 patients (5% of total) at >/=2 years to <5 years; and 22 patients (11% of total) at >/=5 years. The majority of fat necrosis was detected on mammogram (80%) and was asymptomatic (78%). Cosmesis and toxicities were assessed at 3 defined time points: /=5 years of follow-up. Using Harvard criteria, good to excellent cosmetic results were observed in >90% of patients. Breast pain, edema, and erythema diminished with time. Of the 199 cases, there were only 5 ipsilateral breast failures, yielding a 5-year actuarial local recurrence rate of 1.2%. Of these 5 failures, 2 were true recurrences/marginal misses, yielding a 5-year actuarial true recurrence/marginal miss rate of 0.5%. The 5-year actuarial cause-specific survival rate was 99% for APBI patients., Conclusions: In selected patients with early-stage breast cancer, APBI with targeted interstitial brachytherapy offers 5-year results comparable with conventional breast-conserving therapy employing whole-breast radiation therapy. Minimal long-term toxicities were noted, most of which demonstrated continued resolution over time. Acceptable acute (7%) and delayed (4%) infection rates were observed. Fat necrosis was identified with increasing frequency with time, but the majority was asymptomatic. Cosmetic results are good to excellent (>90%). Continued follow-up by the surgeon will be required to determine the long-term efficacy of this alternative treatment approach.

Purpose: We evaluated the potential for differing acute and chronic toxicities between 2 monotherapy methods of image guided conformal brachytherapy, high dose rate (HDR) brachytherapy alone and low dose rate (LDR) permanent palladium seeds., Materials and Methods: A total of 149 patients with biopsy proven, early stage prostate cancer were consecutively treated with interstitial brachytherapy as the sole method of treatment at William Beaumont Hospital between 1999 and 2001. Of the 149, 65 patients were treated with HDR using 192 iridium (192Ir), and 84 patients were treated with LDR using 103 palladium (103Pd). The majority of patients had clinical stage II, T1c or T2a disease, pretreatment prostate specific antigen less than 10 ng/ml and Gleason score 6 or less. Neoadjuvant hormones were used in 36% of patients for gland volume optimization. All treatments were performed transperineally with trans-rectal ultrasound guidance and fluoroscopy for verification of needle/seed positions. The HDR dose was 38 Gy delivered in 4 fractions, 2 times daily during 2 days. The LDR dose was 120 Gy. Acute and chronic toxicities were scored according to the Common Toxicity Criteria scale, version 2.0., Results: Median followup for all patients was 35 months. The 2 treatment groups were well-balanced with respect to age, clinical stage, prostate specific antigen, Gleason score, use of neoadjuvant hormones, pretreatment genitourinary symptoms, implanted gland volume and length of followup. Biochemical control (American Society for Therapeutic Radiology and Oncology definition) was 97% and 98% for LDR and HDR, respectively. HDR brachytherapy alone was associated with decreased acute rates of grade 1 to 3 dysuria (67% versus 36%, p <0.001), urinary frequency/urgency (92% versus 54%, p <0.001) and rectal pain (20% versus 6%, p = 0.017). These differences remained significant when patients who received prior hormonal therapy were excluded from analysis. Selected chronic toxicities were also decreased with HDR, including long-term urinary frequency and urgency, 32% (HDR) vs 56% (103Pd), p = 0.004. There were no differences in the rates of chronic dysuria, urinary incontinence, retention or hematuria. Urethral stricture rates were 8% in the HDR alone group vs 3% for 103 Pd (p = 0.177). The 3-year actuarial impotence rate was 45% for the LDR group and only 16% for HDR. The majority of complications were grade 1. No grade 4 toxicities were encountered in either group. HDR decreased treatment cost by 19%., Conclusions: While HDR (192 iridium) and LDR (103Pd) monotherapy maintained the same biochemical control, the use of HDR brachytherapy as monotherapy was associated with decreased rates of acute urinary frequency, urgency, dysuria and rectal pain compared to LDR. Chronic urinary frequency, urgency and grade 2 rectal toxicities were also decreased with HDR. A dramatic decrease (66%) was noted in the rate of sexual impotency with HDR. In addition, patients treated with HDR did not remain radioactive after treatment. There was a decrease in cost from not purchasing seeds per patient. HDR monotherapy as prostate cancer treatment resulted in the same biochemical control with much lower toxicity. It is an accepted, convenient, cost-effective method of prostate brachytherapy for patients with favorable risk prostate cancer.

Purpose: The clinical significance of postradiotherapy (RT) prostate biopsy characteristics is not well understood relative to the known prognostic factors. We performed a detailed pathologic review of posttreatment biopsy specimens in an attempt to clarify their relationship with clinical outcome and radiation dose., Methods and Materials: Between 1991 and 1998, 78 patients with locally advanced prostate cancer were prospectively treated with external beam RT in combination with high-dose-rate brachytherapy at William Beaumont Hospital and had post-RT biopsy material available for a complete pathologic review. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen level > or =10.0 ng/mL, Gleason score > or =7, or clinical Stage T2b-T3cN0M0. Pelvic external beam RT (46.0 Gy) was supplemented with three (1991-1995) or two (1995-1998) ultrasound-guided transperineal interstitial (192)Ir high-dose-rate implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Post-RT prostate biopsies were performed per protocol at a median interval of 1.5 years after RT. All pre- and post-RT biopsy specimen slides from each case were reviewed by a single pathologist (N.S.G.). The presence and amount of residual cancer, most common RT-effect score, and least amount RT-effect score were analyzed. The median follow-up was 5.7 years. Biochemical failure was defined as three consecutive prostate-specific antigen rises., Results: Forty patients (51%) had residual cancer in the post-RT biopsies. The 7-year biochemical control rate was 79% for patients with negative biopsies vs. 62% for those with positive biopsies with marked RT damage vs. 33% for those with positive biopsies with no or minimal RT damage. A greater percentage of positive pre-RT biopsy cores (p = 0.01), lower total RT dose (p = 0.001), lower dose per implant (p = 0.001), and greater percentage of positive post-RT biopsy cores (p = 0.01) were each associated with biochemical failure (Cox regression, univariate analysis). For patients with <25% positive post-RT biopsy cores, the 7-year biochemical control rate was 81% vs. a 62% biochemical control rate for those with 25-49% positive cores and only 32% for those with > or =50% positive cores (p = 0.01). On Cox multiple regression analysis, only the percentage of positive pre-RT biopsy cores and RT dose remained significantly associated with biochemical failure. Of all the factors analyzed, only the pretreatment cancer volume and lower RT dose were significantly associated with residual cancer and/or residual cancer with no or minimal RT damage. A greater percentage of positive pre-RT biopsy cores was associated with both a positive post-RT biopsy (p = 0.08) and a greater percentage of positive post-RT biopsy cores (p = 0.04). A lower total RT dose was associated with both a positive post-RT biopsy (p = 0.08) and a greater percentage of positive post-RT biopsy cores (p = 0.02). For patients who received <80 Gy (equivalent in 2-Gy fractions), 73% had positive post-RT biopsies vs. a 56% biopsy positivity rate for those who received 84-90 Gy and only 39% for those who received > or =92 Gy (p = 0.07)., Conclusion: Patients with positive post-RT biopsies are more likely to experience biochemical failure, especially when the RT damage is minimal. Patients who have a larger pretreatment tumor volume or receive a lower RT dose are more likely to demonstrate post-RT biopsy positivity and biochemical failure.

Purpose: A new device has been developed with the goal of making breast-conserving therapy more widely available, by making breast brachytherapy as monotherapy simpler and more accurate. This is the first published report on the dosimetric characteristics of this device., Materials and Methods: The experience of a single institution participating in a multi-institutional trial is reported. Twelve patients were enrolled, of whom 8 were treated. Computed tomography scans of all 12 patients were obtained before initiation of treatment. A commercial three-dimensional planning system was used for retrospective detailed analysis of dosimetry, including dose-volume histograms and, in selected patients, skin dose distributions. These data were compared to those of a similar group of patients, analyzed previously, that was treated with interstitial high-dose-rate brachytherapy., Results: Compared with interstitial brachytherapy, the MammoSite device resulted in a treatment dose that was less uniform, with a mean dose homogeneity index of 0.77 vs. 0.93. Coverage and reproducibility were improved, with a mean D90 (minimum dose to 90% of target volume) of 90.0% of prescribed dose (SD 0.5, range: 89.2-90.8%) vs. 69.8% (SD 7.3, range: 61.1-83.5%) for interstitial brachytherapy., Conclusions: Reproducible placement was easily achieved in this very early experience, indicating a much smaller "learning curve" than for interstitial brachytherapy. Because skin doses can be increased with the use of this device, caution is indicated, although simple maneuvers can significantly reduce skin dose.

Background: Breast-conserving surgery with synchronous 50-kV X-ray intraoperative radiation therapy (TARGIT-IORT) is a convenient form of partial breast irradiation; however, the existing literature supports a wide range of local control rates. Objectives: We investigated the treatment effectiveness and toxic effects of TARGIT-IORT in a patient cohort aged 64 years or older with low-risk breast cancer. Design: Retrospective analysis. Methods: Patients who received breast-conserving surgery with synchronous TARGIT-IORT at a single institution from 2016 to 2019 were reviewed. Additional whole breast irradiation was recommended at the discretion of the treating radiation oncologist. Baseline patient demographics and treatment details were recorded. Acute and chronic toxicities, measured using the Common Terminology Criteria for Adverse Events version 3.0 or 4.0 and breast cosmetic outcomes, using the Harvard Cosmesis score, were recorded. Locoregional recurrence, distant metastasis, and overall survival were recorded, and 5-year rates were estimated using the Kaplan-Meier method. Results: 61 patients were included with a median follow-up of 3.5 years and median age of 72 years. Eight (13%) patients received additional whole breast irradiation, and fifty-four (89%) received adjuvant hormone therapy. There were no local, regional, or distance recurrences. One patient died of complications from COVID-19 infection. Grade 2 + acute and chronic toxicities were observed in 6 (12%) and 7 (14%) patients, respectively. One patient experienced a grade 3 acute toxicity. Cosmetic outcome was "excellent" or "good" in 45 (92%) patients. Conclusions: Breast TARGIT-IORT was well tolerated and conferred excellent disease control in this cohort of patients with low-risk breast cancer. While continued follow-up is required, TARGIT-IORT may be an appropriate treatment option for this population. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study examines the use of three-dimensional conformal external beam radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Four-year data on efficacy, cosmesis, and toxicity are presented. Methods: Patients with Stage O, I, or II breast cancer with lesions ≤3 cm, negative margins, and negative nodes were eligible. The 3D-CRT delivered was 38.5 Gy in 3.85 Gy/fraction. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Disease-free, overall, and cancer-specific survival (DFS, OS, CSS) were recorded. The National Cancer Institute Common Terminology Criteria for Adverse Events (version 3) toxicity scale was used to grade acute and late toxicities. Results: Ninety-four patients are evaluable for efficacy. Median patient age was 62 years with the following characteristics: 68% tumor size <1 cm, 72% invasive ductal histology, 77% estrogen receptor (ER) (+), 88% postmenopausal; 88% no chemotherapy and 44% with no hormone therapy. Median follow-up was 4.2 years (range, 1.3–8.3). Four-year estimates of efficacy were IBF: 1.1% (one local recurrence); INF: 0%; CBF: 1.1%; DF: 3.9%; DFS: 95%; OS: 97%; and CSS: 99%. Four (4%) Grade 3 toxicities (one transient breast pain and three fibrosis) were observed. Cosmesis was rated good/excellent in 89% of patients at 4 years. Conclusions: Four-year efficacy, cosmesis, and toxicity using 3D-CRT to deliver APBI appear comparable to other experiences with similar follow-up. However, additional patients, further follow-up, and mature Phase III data are needed to evaluate thoroughly the extent of application, limitations, and complete value of this particular form of APBI. [Copyright &y& Elsevier]

To examine early and late toxicities, evaluate cosmetic results, and determine the need for reoperation or additional diagnostic procedures in patients treated with accelerated partial breast irradiation (APBI) delivered by way of an interstitial implant in breast-conserving therapy.A total of 199 patients with stage I or II breast cancer were managed with lumpectomy followed by radiation restricted to the tumor bed using an interstitial implant (APBI). Retrospective analyses were performed for early and late toxicities (infection, fat necrosis, breast pain, edema, erythema, fibrosis, pigmentation changes, and telangiectasias), need for reoperation or additional diagnostic procedures, cosmetic results, and local control. Patient selection criteria by the surgeon for referral to RT for APBI included age, tumor size, histology, nodal status, margin status, and absence of extensive intraductal component. Treatment was delivered with either a low-dose or high-dose rate implant. Median follow-up was 5.7 years, and 54% of the patients were followed-up for >7 years.Infections developed in 22 of 199 (11%) patients: 7% early (≤1 month after implant removal) and 4% late (>1 month after implant removal). Five of the 22 patients (2% of all patients) required operative intervention for the infection, either incision and drainage or debridement. There was a statistically significant difference between infection rates with open (8.5%) versus closed (2.5%) cavity placement of the interstitial needles (P = 0.005). There was no statistically significant difference between low-dose rate (inpatient) and high-dose rate (outpatient) treatment (P = 0.207). Forty-five patients (23%) had an additional diagnostic procedure to evaluate a suspicious or uncertain finding on physical examination or mammogram. Fibrosis and fat necrosis were found in 26 of the 45 patients. The incidence of fat necrosis increased with time. More patients were found to have fat necrosis after 5 years. One patient had fat necrosis diagnosed at <6 months; 8 patients (4% of total) at ≥6 months to <2 years; 10 patients (5% of total) at ≥2 years to <5 years; and 22 patients (11% of total) at ≥5 years. The majority of fat necrosis was detected on mammogram (80%) and was asymptomatic (78%). Cosmesis and toxicities were assessed at 3 defined time points: ≤6 months, 2 years, and ≥5 years of follow-up. Using Harvard criteria, good to excellent cosmetic results were observed in >90% of patients. Breast pain, edema, and erythema diminished with time. Of the 199 cases, there were only 5 ipsilateral breast failures, yielding a 5-year actuarial local recurrence rate of 1.2%. Of these 5 failures, 2 were true recurrences/marginal misses, yielding a 5-year actuarial true recurrence/marginal miss rate of 0.5%. The 5-year actuarial cause-specific survival rate was 99% for APBI patients.In selected patients with early-stage breast cancer, APBI with targeted interstitial brachytherapy offers 5-year results comparable with conventional breast-conserving therapy employing whole-breast radiation therapy. Minimal long-term toxicities were noted, most of which demonstrated continued resolution over time. Acceptable acute (7%) and delayed (4%) infection rates were observed. Fat necrosis was identified with increasing frequency with time, but the majority was asymptomatic. Cosmetic results are good to excellent (>90%). Continued follow-up by the surgeon will be required to determine the long-term efficacy of this alternative treatment approach. [Copyright &y& Elsevier]