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Purpose: High dose-rate (HDR) brachytherapy is commonly administered as a boost to external beam radiation therapy (EBRT). Our purpose was to compare toxicity with increasingly hypofractionated EBRT in combination with a single 15 Gy HDR boost for men with intermediate-risk prostate cancer., Methods and Materials: Forty-two men were enrolled on this phase IB clinical trial to one of three EBRT dose cohorts: 10 fractions, seven fractions, or five fractions. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition., Results: With a median follow up of 36 months, the biochemical disease-free survival was 95.5%. One man developed metastatic disease at 5 years. There was no significant minimally important difference in EPIC PRO for either urinary, bowel, or sexual domains. There was one acute Grade 3 GI and GU toxicity, but no late Grade 3 GU or GI toxicities., Conclusion: Fifteen gray HDR brachytherapy followed by a five fraction SBRT approach results in high disease control rates and low toxicity similar to previously reported HDR protocols with significant improvement in patient convenience and resource savings. While mature results with longer follow up are awaited, this treatment approach may be considered a safe and effective option for men with intermediate-risk disease., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Aim: Hyperthermia (HT) has been shown to improve clinical response to radiation therapy (RT) for cancer. Synergism is dramatically enhanced if HT and RT are combined simultaneously, but appropriate technology to apply treatments together does not exist. This study investigates the feasibility of delivering HT with RT to a 5-10mm annular rim of at-risk tissue around a tumor resection cavity using a temporary thermobrachytherapy (TBT) balloon implant., Methods: A balloon catheter was designed to deliver radiation from High Dose Rate (HDR) brachytherapy concurrent with HT delivered by filling the balloon with magnetic nanoparticles (MNP) and immersing it in a radiofrequency magnetic field. Temperature distributions in brain around the TBT balloon were simulated with temperature dependent brain blood perfusion using numerical modeling. A magnetic induction system was constructed and used to produce rapid heating (>0.2°C/s) of MNP-filled balloons in brain tissue-equivalent phantoms by absorbing 0.5 W/ml from a 5.7 kA/m field at 133 kHz., Results: Simulated treatment plans demonstrate the ability to heat at-risk tissue around a brain tumor resection cavity between 40-48°C for 2-5cm diameter balloons. Experimental thermal dosimetry verifies the expected rapid and spherically symmetric heating of brain phantom around the MNP-filled balloon at a magnetic field strength that has proven safe in previous clinical studies., Conclusions: These preclinical results demonstrate the feasibility of using a TBT balloon to deliver heat simultaneously with HDR brachytherapy to tumor bed around a brain tumor resection cavity, with significantly improved uniformity of heating over previous multi-catheter interstitial approaches. Considered along with results of previous clinical thermobrachytherapy trials, this new capability is expected to improve both survival and quality of life in patients with glioblastoma multiforme.

Purpose: Although current Delphi Consensus guidelines do not recommend a specific definition of biochemical recurrence after partial gland therapy, these guidelines acknowledge that serial prostate-specific antigen (PSA) tests remain the best marker for monitoring disease after treatment. The purpose of this study was to determine whether PSA velocity at failure per the Phoenix (nadir + 2 ng/mL) definition is associated with metastasis and prostate cancer-specific mortality (PCSM) in a cohort of patients who experienced PSA failure after partial gland therapy., Methods: Between 1997 and 2007, 285 patients with favorable risk prostate cancer underwent partial prostate brachytherapy to the peripheral zone. PSA velocity was calculated for 94 patients who experienced PSA failure per the Phoenix (nadir + 2) definition. Fine and Gray competing risks regression was performed to determine whether PSA velocity and other clinical factors were associated with metastasis and PCSM., Results: The median time to PSA failure was 4.2 years (interquartile range: 2.2, 7.9), and the median followup time after PSA failure was 6.5 years (3.5-9.7). Seventeen patients developed metastases, and five experienced PCSM. On multivariate analysis, PSA velocity ≥3.0 ng/mL/year (adjusted hazard ratio 5.97; [2.57, 13.90]; p < 0.001) and PSA nadir (adjusted hazard ratio 0.39; [0.24, 0.64]; p < 0.001) were significantly associated with metastasis. PSA velocity ≥3.0 ng/mL/year was also associated with PCSM (HR 15.3; [1.8, 128.0]; p = 0.012) on univariate analysis., Conclusions: Rapid PSA velocity at PSA failure after partial gland treatment may be prognostic for long-term outcomes., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: We sought to determine whether patients with high-volume, low-risk prostate cancer are suitable candidates for ultrasound-guided brachytherapy, monotherapy alone, without supplemental external beam radiation., Materials and Methods: The study cohort comprised 200 consecutive patients who received ultrasound.guided monotherapy from November 02, 1998 to March 26, 2010. Real.time intraoperative treatment planning was performed for all patients. 145. Gy with I125 was prescribed to the prostate with no margin. The primary endpoint was time to prostate-specific antigen. (PSA) failure using the phoenix definition. Cox multivariable regression analysis was used to determine the factors significantly associated with time to PSA failure., Results: Median follow-up was 59 months (range 1.2-146.8 months). The median PSA was 5.0 ng/ml. For the overall cohort, both 5- and 8-year PSA failure-free survival was 92.3% (95% confidence interval [95% CI]: 86.5-95.7%). Low-risk patients per the NCCN criteria had 5- and 8-year PSA failure-free survival of 93.6%. On cox multivariable analysis, only baseline PSA (adjusted hazard ratio: 1.29 [95% CI: 1.02-1.65], P = 0.036) was associated with outcome. Among patients with Conclusions: Our analysis indicates that patients with a high number of cores positive for cancer can be adequately treated with modern brachytherapy as monotherapy and be spared the additional morbidity and cost of supplemental external beam radiation or androgen deprivation therapy.

High-dose rate brachytherapy (HDR-BT) monotherapy and robotic arm (i.e., CyberKnife) stereotactic body radiation therapy (SBRT) are emerging technologies that have become popular treatment options for prostate cancer. Proponents of both HDR-BT monotherapy and robotic arm SBRT claim that these modalities are as efficacious as intensity-modulated radiation therapy in treating prostate cancer. Moreover, proponents of robotic arm SBRT believe it is more effective than HDR-BT monotherapy because SBRT is non-invasive, touting it as 'virtual HDR-BT.' We perform a comparative effective analysis of the two technologies. The tumor control rates and toxicities of HDR-BT monotherapy and robotic arm SBRT are promising. However, at present, it would be inappropriate to state that HDR-BT monotherapy and robotic arm SBRT are as efficacious or effective as other treatment modalities for prostate cancer, which have stronger foundations of evidence. Studies reporting on these technologies have relatively short follow-up time, few patients and are largely retrospective.

Purpose: Prostate volume greater than 50cc is traditionally a relative contraindication to prostate seed implantation (PSI), but there is little consensus regarding prostate size and clinical outcomes. We report biochemical control and toxicity after low-dose-rate PSI and compare outcomes according to the prostate size., Methods and Materials: A total of 429 men who underwent low-dose-rate PSI between 1998 and 2009 were evaluated. Median followup was 38.7 months. Patients were classified by prostate volume into small, medium, and large subgroups. Differences were analyzed using the Mann-Whitney and Pearson's χ(2) tests for continuous and categorical variables, respectively. Cox proportional hazards regression models were used to evaluate effect of prostate size on outcomes., Results: Patient pretreatment factors were balanced between groups except for age (p=0.001). The 10-year actuarial freedom from biochemical failure for all patients treated with PSI was 96.3% with no statistically significant difference between large vs. small/medium prostate size (90% vs. 96.6%, p=0.47). In a multivariate analysis, plan type (hazard ratio [HR]=0.25, p=0.03), dose to 90% of the gland (D90: HR=0.98, p=0.02), volume receiving 200Gy (V200: HR=0.98, p=0.026), and biologic effective dose (HR=0.99, p=0.045), but not prostate size (HR=2.27, p=0.17) were significantly associated with freedom from biochemical failure. Prostate size was not significantly associated with time to maximum American Urologic Association score., Conclusion: In men with large prostates, the PSI provides biochemical control and temporal changes in genitourinary toxicity that are comparable with men having smaller glands. Accurate dose optimization and delivery of PSI provides the best clinical outcomes regardless of gland size., (Published by Elsevier Inc.)

Studies of dose-escalated external beam radiation therapy (EBRT) and low dose rate brachytherapy (LDR-BT) have shown excellent rates of tumor control and cancer specific survival. Moreover, LDR-BT combined with EBRT (i.e. "LDR-BT boost") is hypothesized to improve local control. While phase II trials with LDR-BT boost have produced mature data of outcomes and toxicities, high dose rate (HDR)-BT has been growing in popularity as an alternative boost therapy. Boost from HDR-BT has theoretical advantages over LDR-BT, including improved cancer cell death and better dose distribution from customization of catheter dwell times, locations, and inverse dose optimization. Freedom from biochemical failure rates at five years for low-, intermediate-, high-risk, and locally advanced patients have generally been 85-100%, 80-98%, 59-96%, and 34-85%, respectively. Late Radiation Therapy Oncology Group grade 3-4 toxicities have also been encouraging with <6% of patients experiencing any toxicity. Limitations of current HDR-BT boost studies include reports of only single-institution experiences, and unrefined reports of toxicity or patient quality of life. Comparative effectiveness research will help guide clinicians in selecting the most appropriate treatment option for individual patients based on risk-stratification, expected outcomes, toxicities, quality of life, and cost., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Low-dose rate brachytherapy (LDR-BT), involving implantation of radioactive seeds into the prostate, is an established monotherapy for most low-risk and select intermediate- and high-risk prostate cancer patients. High-dose rate brachytherapy (HDR-BT) is an advanced technology theorized to be more advantageous than LDR-BT from a radiobiological and radiophysics perspective, to the patient himself, and in terms of resource allocation. Studies of HDR-BT monotherapy have encouraging results in terms of biochemical control, patient survival, treatment toxicity and erectile preservation. However, there are still certain limitations that preclude recommending HDR-BT monotherapy for prostate cancer outside the setting of a clinical trial. HDR-BT monotherapy should be considered experimental at present.

External beam radiation therapy (EBRT) combined with brachytherapy (BT) is an attractive treatment option for select patients with clinically localized prostate cancer. Either low- or high-dose rate BT may be combined with EBRT ('LDR-BT boost,' 'HDR-BT boost,' respectively). HDR-BT boost has potential theoretical benefits over LDR-BT boost or external beam radiation therapy monotherapy in terms of radiobiology, radiophysics and patient convenience. Based on prospective studies in this review, freedom from biochemical failure (FFBF) rates at 5 years for low-, intermediate- and high-risk patients have generally been 85-100%, 68-97%, 63-85%, respectively; late Radiotherapy and Oncology Group Grades 3 and 4 genitourinary and gastrointestinal toxicities are seen in <8% of patients. HDR-BT boost is now a relatively well-established treatment modality for certain intermediate-risk and high-risk prostate cancer patients, though limitations exist in drawing conclusions from the currently published studies.

Purpose: We report updated results of magnetic resonance imaging guided partial prostate brachytherapy and propose a definition of biochemical failure following focal therapy., Materials and Methods: From 1997 to 2007, 318 men with cT1c, prostate specific antigen less than 15 ng/ml, Gleason 3 + 4 or less prostate cancer received magnetic resonance imaging guided brachytherapy in which only the peripheral zone was targeted. To exclude benign prostate specific antigen increases due to prostatic hyperplasia, we investigated the usefulness of defining prostate specific antigen failure as nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year. Cox regression was used to determine the factors associated with prostate specific antigen failure., Results: Median followup was 5.1 years (maximum 12.1). While 36 patients met the nadir +2 criteria, 16 of 17 biopsy proven local recurrences were among the 26 men who also had a prostate specific antigen velocity greater than 0.75 ng/ml per year (16 of 26 vs 1 of 10, p = 0.008). Using the nadir +2 definition, prostate specific antigen failure-free survival for low risk cases at 5 and 8 years was 95.1% (91.0-97.3) and 80.4% (70.7-87.1), respectively. This rate improved to 95.6% (91.6-97.7) and 90.0% (82.6-94.3) using nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year. For intermediate risk cases survival was 73.0% (55.0-84.8) at 5 years and 66.4% (44.8-81.1) at 8 years (the same values as using nadir +2 with prostate specific antigen velocity greater than 0.75 ng/ml per year)., Conclusions: Requiring a prostate specific antigen velocity greater than 0.75 ng/ml per year in addition to nadir +2 appears to better predict clinical failure after therapies that target less than the whole gland. Further followup will determine whether magnetic resonance imaging guided brachytherapy targeting the peripheral zone produces comparable cancer control to whole gland treatment in men with low risk disease. However, at this time it does not appear adequate for men with even favorable intermediate risk disease., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented., Methods: Intermediate-risk patients per Memorial Sloan-Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I125 (100 Gy) or Pd103 (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease-free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate-specific antigen rises>1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival., Results: Sixty-one of 63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six-year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six-year overall survival was 96.1%., Conclusions: In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer., (Copyright © 2011 American Cancer Society.)

Purpose: Transperineal prostate brachytherapy (TPPB) can be used with external beam radiation therapy (EBRT) to provide a high-dose conformal boost to the prostate. The results of a multicenter Phase II trial assessing safety of combination of EBRT and TPPB boost with androgen suppression (AST) in treatment of intermediate-risk prostate cancer are present here., Materials and Methods: Patients had intermediate-risk prostate cancer. Six months of AST was administered. EBRT to the prostate and seminal vesicles was administered to 45Gy followed by TPPB using either (125)I or (103)Pd to deliver an additional 100Gy or 90Gy. Toxicity was graded using the National Cancer Institute CTC version 2 and the Radiation Therapy Oncology Group late radiation morbidity scoring systems., Results: Sixty-three patients were enrolled. Median follow-up was 38 months. Side effects of AST including sexual dysfunction and vasomotor symptoms were commonly observed. Apart from erectile dysfunction, short-term Grade 2 and 3 toxicity was noted in 21% and 7%, primarily genitourinary related. Long-term Grade 2 and 3 toxicities were noted in 13% and 3%. Two patients had Grade 3 dysuria that resolved with longer follow-up. The most common Grade 2 long-term toxicity was urinary frequency (5%). No biochemical or clinical evidence of progression was noted for the entire cohort., Conclusions: In a cooperative group setting, combination EBRT and TPPB boost with 6 months of AST was generally well tolerated with expected genitourinary and gastrointestinal toxicities. Further follow-up will be required to fully assess long-term toxicity and cancer control.

External-beam radiation therapy (EBRT) combined with brachytherapy is an attractive treatment option for selected patients with clinically localized prostate cancer. This therapeutic strategy offers dosimetric coverage if local-regional microscopic disease is present and provides a highly conformal boost of radiation to the prostate and immediate surrounding tissues. Either low-dose-rate (LDR) permanent brachytherapy or high-dose-rate (HDR) temporary brachytherapy can be combined with EBRT; such combined-modality therapy (CMT) is typically used to treat patients with intermediate-risk to high-risk, clinically localized disease. Controversy persists with regard to indications for CMT, choice of LDR or HDR boost, isotope selection for LDR, and integration of EBRT and brachytherapy. Initial findings from prospective, multicenter trials of CMT support the feasibility of this strategy. Updated results from these trials as well as those of ongoing and new phase III trials should help to define the role of CMT in the management of prostate cancer. In the meantime, long-term expectations for outcomes of CMT are based largely on the experience of single institutions, which demonstrate that CMT with EBRT and either LDR or HDR brachytherapy can provide freedom from disease recurrence with acceptable toxicity.

Purpose: This study was performed to define the rectal dose constraint that would predict late rectal bleeding requiring argon plasma coagulation (APC) following prostate brachy mono-therapy., Methods and Materials: Between February 1999 and April 2002, 91 patients with low risk prostate cancer underwent permanent I(125) radioactive seed implantation without the use of supplemental external beam radiation or androgen suppression therapy. Patients received both CT and MRI scans 6 weeks postimplant for evaluation of dosimetry. The CT and MRI scans were fused. Rectal volumes were contoured on the T2 weighted MR images. For those patients requiring APC, the date on which a patient reported rectal bleeding was recorded. A Cox regression analysis was performed to assess whether there was a significant association between the rectal volume (continuous) exceeding 100 Gy time rectal bleeding. Comparisons of estimates of rectal bleeding requiring APC were made using a 2-sided log rank test., Results: There was a significant association (hazard ratio = 5.6 [95% confidence interval: 1.3, 23.8]; P = 0.002) between the rectal volume exceeding 100 Gy and rectal bleeding requiring APC. After a median follow-up of 4.25 (1-6) years, no patient with less than a median value of 8 cc of rectum exceeding 100 Gy required APC, whereas 20% (P = 0.004) were estimated to require APC within 3 years following treatment., Conclusions: Keeping the rectal volume receiving more than 100 Gy below 8 cc will minimize the risk of rectal bleeding requiring APC following I(125) permanent prostate brachy mono-therapy.

Background: This study was designed to estimate the rates of late genitourinary (GU) and rectal toxicity after magnetic resonance image (MRI)-guided prostate brachytherapy exclusively or in conjunction with external beam radiation therapy (EBRT)., Methods: Between November 1997 and April 2002, 201 patients with category T1C prostate carcinoma (according to the 2002 American Joint Committee on Cancer staging criteria), prostate specific antigen levels < 10 ng/mL, and biopsy Gleason score 3 + 4 disease were treated with MRI-guided brachytherapy exclusively or in conjunction with EBRT. The MRI-guided technique was designed to spare the urethra based on delivery of the prescription dose to the peripheral zone exclusively. The Kaplan-Meier method was used to estimate rates of freedom from late GU and rectal toxicity. Comparisons were made using a log-rank test., Results: At a median follow-up of 2.8 years (range, 0.5-5.0 years), the 4-year estimates of rectal bleeding requiring coagulation for patients who underwent implantation therapy, compared with patients who received combined-modality therapy, were 8% versus 30%, respectively (log-rank P value = 0.0001). Although erectile dysfunction was common (range, 82-93%), with the use of sildenafil citrate (Viagra), it was estimated that at least two-thirds of patients had erectile function comparable to or superior to baseline function, independent of whether they received monotherapy or combined-modality therapy (P = 0.46). The 4-year estimate of freedom from radiation cystitis was 100% versus 95% (P = 0.01) for patients who received monotherapy and patients who received combined-modality therapy, respectively. No urethral strictures were observed, and no patients underwent postimplantation transurethral resection of the prostate., Conclusions: In the current study, rectal bleeding after MRI-guided prostate brachymonotherapy was infrequent, and urethral and bladder toxicity is reported to be rare and may be attributed to the urethral-sparing technique of the MRI-guided approach., (Copyright 2003 American Cancer Society.)

Purpose: Larger prostate gland volumes have been associated with long-term urinary morbidity in prostate interstitial radiation therapy utilizing ultrasound image guidance technique. This study was performed to identify the clinical and technical predictors of acute urinary retention following magnetic-resonance (MR)-guided prostate interstitial brachytherapy., Methods and Materials: Fifty patients underwent MR-guided prostate brachytherapy between December 1997 and March 1999. Patient selection was limited to men with stage T1cNXM0 disease, PSA of less than10 ng/mL, biopsy Gleason score not more than 3 + 4, and endorectal coil MR stage T2 disease. Dosimetry plans were developed in the operating room and (125)Iodine sources were implanted using MR real-time guidance. The peripheral zone (PZ) of the prostate gland was defined as the clinical target volume (CTV) and the minimum prescribed dose to the CTV was 137 Gy. The volumes of the PZ, transition zone (TZ), and total prostate gland volume were also determined by MR. Individual source strength ranged from 0.35 to 0.54 microGym(2)/h (NIST 99, median 0.46 microGym(2)/h) and the total implanted activity ranged from 17.0 to 43.1 mCi (median, 28.1 mCi) using 43-120 seeds (median, 79). The seeds were placed using MR-compatible biopsy needles (14-28, median, 19)., Results: The ability of clinical (MR defined prostate, PZ, and TZ volumes) and technical (number of catheters, number of seeds implanted, and total activity) factors to predict AUR for 50 men undergoing MR-guided prostate interstitial brachytherapy were evaluated using univariable and logistic regression multivariable analyses. Six men (12%) experienced AUR within 24 h after removal of the Foley catheter subsequent to prostate brachytherapy. The total number of seeds (p = 0.05), MR determined prostate volume (p < 0.01), and the MR-determined TZ volume (p < 0.01) were significant predictors of AUR on univariable analysis. Utilizing a multivariable logistic regression analysis, the TZ volume was the only significant predictor of AUR (p < 0.01). The prostate volume is highly correlated to the TZ volume (Spearman correlation coefficient of 0. 91) and was thus significant in the univariable analysis; however, the prostate volume did not add prognostic value in multivariable analysis., Conclusion: Benign prostatic hyperplasia (BPH) resulting in an enlarged TZ volume, is the most important predictor of AUR following MR-guided prostate interstitial radiation therapy. Although AUR was significant (60%) in men with moderate BPH (TZ volume >/= 50 cc), it was also self-limiting.

Purpose: A large number of men are diagnosed with early-stage prostate cancer as a result of prostate-specific antigen (PSA) screening. For many of these men, prostatectomy results in long-term freedom from biochemical and clinical failure. Despite limited follow-up data, ultrasound-guided prostate brachytherapy has gained acceptance as a treatment for early-stage prostate cancer, in part due to its favorable side effect profile and brief recovery period. We report on the use of three-dimensional real-time magnetic resonance (MR) guidance, which has several advantages compared with biplanar ultrasound guidance for prostate brachytherapy, including enhanced geometric and dosimetric feedback during the procedure., Materials and Methods: Median clinical target volume coverage of 96% was achieved using MR guidance. The ability to define more precisely the clinical target volume with MR and the use of real-time assessment of dose distribution resulted in an excellent acute side effect profile. Only 19% of patients required oral alpha1 blockers for postimplant urethritis and 9% required temporary reinsertion of the Foley catheter due to acute urinary obstruction., Conclusions: These results compare favorably to those of ultrasound-guided brachytherapy. Further follow-up is needed to ascertain the impact this technique will have on cancer control and long-term quality of life.