Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy

PurposeTo determine the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and present short-term biochemical no evidence of disease (bNED) rates after high-dose-rate brachytherapy (HDR-B) monotherapy.Methods and MaterialsBetween October 2003 and June 2006, 36 patients with low (28) and intermediate (8) risk prostate cancer (PCA) were treated by HDR-B monotherapy. All patients received one implant and four fractions of 9.5 Gy within 48 h for a total prescribed dose (PD) of 38 Gy. Five patients received hormonal therapy (HT). Median age was 63.5 years and median followup was 3 years (range, 0.4–4 years). Toxicity was scored according to the CTCAE version 3.0. Biochemical failure was defined according to the Phoenix criteria.ResultsAcute and late Grade 3 GU toxicity was observed in 1 (3%) and 4 (11%) patients, respectively. Grade 3 GI toxicity was absent. The three- year bNED survival rate was 100%. The sexual preservation rate in patients without HT was 75%. Late Grade 3 GU toxicity was associated with the planning target volume (PTV) V₁₀₀ (% PTV receiving ≥100% of the PD; p = 0.036), D₉₀ (dose delivered to 90% of the PTV; p = 0.02), and the urethral V₁₂₀ (urethral volume receiving ≥120% of the PD; p = 0.043). The urethral V₁₂₀ was associated with increased PTV V₁₀₀ (p < 0.001) and D₉₀ (p = 0.003).ConclusionsAfter HDR-B monotherapy, late Grade 3 GU toxicity is associated with the urethral V₁₂₀ and the V₁₀₀ and D₉₀ of the PTV. Decrease of the irradiated urethral volume may reduce the GU toxicity and potentially improve the therapeutic ratio of this treatment.     

Urethral dosimetry and toxicity with high-dose-rate interstitial brachytherapy for vaginal cancer

PurposeThe tolerance and complication rates of the urethra are unknown for the interstitial high-dose-rate brachytherapy (HDR-BT) for vaginal cancer.Methods and MaterialsPatients with vaginal cancer near/involving the urethra who were treated with HDR-BT between 2008 and 2011 were included. Patients received mean external beam dose of 48.0 Gy followed by mean HDR-BT dose of 4.5 Gy/fraction for five fractions. With CT-based planning, the urethra was contoured from the bladder neck to the meatus. Doses were converted to the biologically equivalent dose in 2 Gy/fraction (EQD₂).ResultsA total of 16 patients were included, and the EQD₂ D₉₀ was 74.9 Gy. The urethral volume was 1.31 cm³, and the EQD₂ to 0.1 and 1 cm³ were 76.2 and 48.9 Gy, respectively. Two of the 6 patients with urethral involvement developed urethral necrosis. The D₉₀ for these 2 patients was 76.8 Gy, and the urethral doses to 0.1 and 1 cm³ were 95.1 and 45.8, respectively. Those who developed severe urethral toxicity had a trend to urethral EQD₂ (95.1 Gy vs. 73.4 Gy, p = 0.1) and significantly higher dose per fraction of HDR-BT to 0.1 cm³ of the urethra (5.7 Gy vs. 3.7 Gy, p = 0.02) when compared with those who did not develop severe urethral toxicity.ConclusionsThis study is among the first to assess urethral dosimetry for patients treated with HDR-BT for vaginal cancer. Patients who received five fractions of higher than 5 Gy/fraction to 0.1 cm³ of urethra (estimated EQD₂ of 85 Gy) are at increased risk of severe urethral toxicity.     

Complications and side effects of high-dose-rate prostate brachytherapy

PurposeTo describe technical challenges and complications encountered during and after high-dose-rate prostate brachytherapy (HDR-BT) and review management of these complications.Methods and MaterialsThe authors performed a systematic review of the literature on toxicities encountered after prostate HDR-BT +/− external beam radiotherapy. A total of 397 studies were identified, of which 64 were included. A focused review of literature regarding the management of acute and late toxicities also performed.ResultsMost acute toxicities include grade 0–2 genitourinary and gastrointestinal toxicity. Overall, Grade 3+ Common Terminology Criteria for Adverse Events toxicity after HDR-BT was low [genitourinary: 0–1%; gastrointestinal 0–3%]. Rates of fistula formation were <1%, and radiation cystitis/proctitis were <14% and more commonly reported in cohorts treated with HDR-BT boost and external beam radiotherapy.ConclusionsHDR-BT both as monotherapy or combined with external beam radiotherapy for prostate cancer is well tolerated. Serious complications are rare.     

Dosimetric impact of inter-observer catheter reconstruction variability in ultrasound-based high-dose-rate prostate brachytherapy

PurposeTo investigate the dosimetric impact of interobserver catheter reconstruction variability in transrectal ultrasound–guided prostate high-dose-rate (HDR) brachytherapy.Methods and MaterialsTwenty consecutive patients with intermediate- or high-risk prostate cancer were treated with a single, 15-Gy HDR brachytherapy boost as part of this study. The treated plan was used as the study reference plan (P_R). Three expert treatment planners (observers) manually reconstructed the catheter paths on the static three-dimensional transrectal ultrasound images, and new plans were generated from the updated positions (P_OBS); subsequently, the dwell time and positions from the P_OBS plans were superimposed on the P_R catheter paths to evaluate the dosimetric effect of the interobserver variations (P_EVAL). Plans from each group were stratified by observer and by number of catheters (12 or 16) and then compared using a one-way Kruskal–Wallis H test with post hoc Mann–Whitney U tests reserved for significant variations (α = 0.05).ResultsGreater than 98.9% of catheter reconstruction variations were <3 mm. When stratified by observer, there was a significant decrease (p << 0.05) in planning target volume (PTV) V_100% and increases in the urethral D_max between the P_OBS plans propagated to the P_R catheter paths and dosimetry evaluated and P_R plans only. Stratification of plans by catheter number showed nonclinically significant decreases in PTV V_100%, and D_90% and increases in urethral D_max for the 12-catheter plans.ConclusionsLimiting interobserver variability, and its effects on prostate HDR brachytherapy plan quality, is critical to achieving good dosimetric outcomes; small variations in catheter reconstruction may translate to inadequate PTV coverage, excessive urethral dose, or both.     

Predictors of urinary toxicity with MRI-assisted radiosurgery for low-dose-rate prostate brachytherapy

PurposeMRI-assisted radiosurgery (MARS) is a modern technique for prostate brachytherapy that provides superior soft tissue contrast. The purpose of this analysis was to evaluate treatment planning factors associated with urinary toxicity, particularly damage to the membranous urethra (MUL) and external urethral sphincter (EUS), after MARS.Material and MethodsWe retrospectively reviewed 227 patients treated with MARS. Comparisons were made between several factors including preimplantation length of the MUL and EUS dosimetric characteristics after implantation with longitudinal changes in American Urological Association (AUA) urinary symptom score.ResultsRates of grade 3 urinary incontinence and obstructive urinary symptoms were 4% and 2%. A piecewise mixed univariate model revealed that MUL and V₂₀₀, V₁₅₀, V₁₂₅, and D₅ to the EUS were all associated with increased rates of urinary toxicity over time. On univariate logistic regression, MUL >14.2 mm (odds ratio [OR] 2.03 per cm³, 95% confidence interval [CI] 1.10–3.77, p = 0.025), V₁₂₅ to the EUS (OR 3.21 cm³, 95% CI 1.18–8.71, p = 0.022), and use of the I-125 isotope (OR 3.45, 95% CI 1.55–7.70, p = 0.001) were associated with subacute urinary toxicity (i.e., that occurring at 4–8 months). Optimal dose-constraint limits to the EUS were determined to be V₂₀₀ < 0.04 cm³ (p = 0.002), V₁₅₀ < 0.12 cm³ (p = 0.041), V₁₂₅ < 0.45 cm³ (p = 0.033), D₃₀ < 160 Gy (p = 0.004), and D₅ < 218 Gy (p = 0.016).ConclusionsMARS brachytherapy provides detailed anatomic information for treatment planning, implantation, and quality assurance. Overall rates of urinary toxicity are low; however, several dosimetric variables associated with the EUS were found to correlate with urinary toxicity.     

A surrogate urethra for real-time planning of high-dose-rate prostate brachytherapy

PurposeThis study characterizes prostatic urethra cross-section to develop a surrogate urethra for accurate prediction of urethral dose during real-time high-dose-rate prostate brachytherapy.Materials and MethodsArchived preoperative transrectal ultrasound images from 100 patients receiving low-dose-rate prostate brachytherapy were used to characterize the prostatic urethra, contoured on ultrasound using aerated gel. Consensus contours, defined using majority vote, described commonalities in cross-sectional shape across patients. Potential simplified surrogates were defined and evaluated against the true urethra. The best performing surrogate, a circle of varying size (CS) was retrospectively contoured on 85 high-dose-rate prostate brachytherapy treatment plans. Dose to this recommended surrogate was compared with urethral doses estimated by the standard 6 mm circle surrogate.ResultsClear variation in urethral cross-sectional shape was observed along its length and between patients. The standard circle surrogate had low predictive sensitivity (61.1%) compared with true urethra because of underrepresentation of the verumontanum midgland. The CS best represented the true urethra across all validation metrics (dice: 0.73, precision: 67.0%, sensitivity: 83.2%, conformity: 0.78). Retrospective evaluation of planned doses using the CS surrogate resulted in significant differences in all reported urethral dose parameters compared with the standard circle, with the exception of D_100%. The urethral dose limit (115%) was exceeded in 40% of patients for the CS surrogate.ConclusionsThe proposed CS surrogate, consisting of circles of varying diameter, is simple yet better represents the true urethra compared with the standard 6 mm circle. Higher urethral doses were predicted using CS, and the improved accuracy of CS may offer increased predictive power for urethral toxicity, a subject of future work.     

Manual vs. automated implantation of seeds in prostate brachytherapy: Oncologic results from a single-center study

PurposeThe objective of this study was to study survival and tolerance of prostate cancer patients treated with ¹²⁵I permanent interstitial brachytherapy by automated vs. manual implantation of seeds.Methods and MaterialsBetween 2002 and 2010, 349 selected patients were treated with ¹²⁵I brachytherapy by the same team: from 2002 to April 2005, 65 patients with linked seeds and then 284 patients treated using Nucletron First System automated implantation. We analyzed biochemical recurrence-free survival (bRFS) rates and toxicities (univariate and multivariate analyses).ResultsTwo hundred seventy-seven (79.4%) and 69 patients (19.8%) with low- and intermediate-risk disease were treated, respectively (median follow-up: 64 months). The 5-year bRFS rate was 93.1% (95% confidence interval 89.3–95.6) for the entire cohort. The 5-year bRFS rates were 93.4% and 91.7% for patients with low- and intermediate-risk disease, respectively (p = 0.42). In univariate and multivariate analyses, there was no statistically significant difference in the 5-year bRFS rate depending on the implantation technique (93.1% vs. 91.8%, respectively, for automated and linked seeds; p = 0.53). In univariate analysis, only D₉₀ prostate (dose delivered to 90% of the prostate) <140 Gy (p = 0.01), lack of prostate-specific antigen bounce (p = 0.008), and nadir prostate-specific antigen >0.11 (p = 0.01) were predictive factors for bRFS. We observed Grade 3 urethritis in 7 patients (2%), urinary incontinence in 2 patients (0.7%), and Grade 4 proctitis in 2 patients (0.7%).ConclusionsIn this large single-center series, brachytherapy for selected localized prostate cancer achieved excellent rates of biochemical control at 5 years (93.1%) with an acceptable toxicity profile, irrespective of the implantation technique used.     

Conventional vs machine learning–based treatment planning in prostate brachytherapy: Results of a Phase I randomized controlled trial

PurposeThe purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning–based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated.Materials and Methods41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning–based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V_150% isodose volume between either the PIPA—or conventional—and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30.Results21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D_90%, V_100%, rectum V₁₀₀, or rectum D_1cc between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05).ConclusionsA machine learning–based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners.     

Placement of an absorbable rectal hydrogel spacer in patients undergoing low-dose-rate brachytherapy with palladium-103

PurposeRates of rectal toxicity after low-dose-rate (LDR) brachytherapy for prostate cancer are dependent on rectal dose, which is associated with rectal distance from prostate and implanted seeds. Placement of a hydrogel spacer between the prostate and rectum has proven to reduce the volume of the rectum exposed to higher radiation dose levels in the setting of external beam radiotherapy. We present our findings with placing a rectal hydrogel spacer in patients following LDR brachytherapy, and we further assess the impact of this placement on dosimetry and acute rectal toxicity.Methods and MaterialsBetween January 2016 and April 2017, 74 patients had placement of a hydrogel spacer, immediately following a Pd-103 seed-implant procedure. Brachytherapy was delivered as follows: as a monotherapy to 26 (35%) patients; as part of planned combination therapy with external beam radiotherapy to 40 (54%) patients; or as a salvage monotherapy to eight (11%) patients. Postoperative MRI was used to assess separation achieved with rectal spacer. Acute toxicity was assessed retrospectively using Radiation Oncology Therapy Group radiation toxicity grading system. Rectal dosimetry was compared with a consecutive cohort of 136 patients treated with seed implantation at our institution without a spacer, using a 2-tailed paired Student's t test (p < 0.05 for statistical significance).ResultsOn average, 11.2-mm (SD 3.3) separation was achieved between the prostate and the rectum. The resultant mean rectal volume receiving 100% of prescribed dose (V_100%), dose to 1 cc of rectum (D_1cc), and dose to 2 cc of rectum (D_2cc) were 0 (SD 0.05 cc), 25.3% (SD 12.7), and 20.5% (SD 9.9), respectively. All rectal dosimetric parameters improved significantly for the cohort with spacer placement as compared with the nonspacer cohort. Mean prostate volume, prostate V₁₀₀ and dose to 90% of gland (D₉₀) were 29.3 cc (SD 12.4), 94.0% (SD 3.81), and 112.4% (SD 12.0), respectively. Urethral D₂₀, D_5cc, and D_1cc were 122.0% (SD 17.27), 133.8% (SD 22.8), and 144.0% (SD 25.4), respectively. After completing all treatments, at the time of first the followup, 7 patients reported acute rectal toxicity—6 experiencing Grade 1 rectal discomfort and 1 (with preexisting hemorrhoids) experiencing Grade 1 bleeding.ConclusionsInjection of rectal spacer is feasible in the post-LDR brachytherapy setting and reduces dose to the rectum with minimal toxicity. Prostate and urethral dosimetries do not appear to be affected by the placement of a spacer. Further studies with long-term followup are warranted to assess the impact on reduction of late rectal toxicity.     

Salvage brachytherapy for recurrent prostate cancer

PurposeTo evaluate the role of salvage prostate brachytherapy for locally recurrent prostate cancer after external beam radiation alone.Methods and MaterialsSixty-nine consecutive patients treated with salvage brachytherapy after a local failure were analyzed. All patients were found to have pathologic proven recurrent prostate cancer at least 2 years after initial therapy and no regional or distant disease on imaging studies. Pd-103 was used with a prescribed pD₉₀ of 100 Gy. In total, 89.9% of patients received androgen suppression (AS) as part of their salvage therapy. Patients whose prostate-specific antigen >5.0 ng/mL while on AS were considered to have castration resistant prostate cancer (CRPC). Patients on AS >6 months before salvage brachytherapy were considered to have delayed therapy. Patients retreated within 5 years after their initial treatment were considered to have early failures.ResultsTotal median followup after salvage therapy was 5.0 years (0.6–13.7). From the date of salvage, 5-year biochemical control for low-risk patients was 85.6%, intermediate-risk patients 74.8%, and high-risk patients 66%. Five-year biochemical control was 73.8% for non-CRPC and 22% for CRPC cases (<0.001). Including and excluding CRPC cases, early treatment after failure vs. delayed treatment was significantly better (p < 0.05). Chronic adverse events were seen in few patients, with genitourinary Grade 3 toxicity of 8.7% and no genitourinary Grade 4 or gastrointestinal Grade 3 or higher toxicities.ConclusionsA subset of failures after definitive radiation is local in nature, and excellent control is possible with salvage brachytherapy.     

Dose to the bladder neck is not correlated with urinary toxicity in patients with prostate cancer treated with HDR brachytherapy boost

PurposeThe purpose of this study was to evaluate whether the dose to bladder neck (BN) is a predictor of acute and late urinary toxicity after high-dose-rate brachytherapy (HDRB) boost for prostate cancer.Methods and MaterialsBetween 2014 and 2016, patients with prostate cancer treated at our institution with external beam radiation therapy and 15 Gy single-fraction HDRB boost for intermediate- and high-risk disease according to D'Amico definition were reviewed. Intraoperative CT scan–based inverse planning and ultrasound-based inverse planning were performed in 173 and 136 patients, respectively. The following structures were prospectively contoured: prostate, urethra, rectum, bladder, and the BN defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. Dose to the BN was reported only, no constraint was applied. Acute and late urinary toxicity were assessed using the International Prostate Symptom Score (IPSS) and the Common Terminology Criteria for Adverse Events v.4.0. Clinical and dosimetry factors associated with urinary toxicity were analyzed using generalized linear models.ResultsA total of 309 patients with median age of 71 years (range 50–89) were included. Median followup was 25 months (range 0–39 months). Using D'Amico definition, 71% of the patients had intermediate-risk disease, whereas 29% had high-risk disease. The mean pretreatment prostate-specific antigen value was 9.65 ng/mL. The mean pretreatment, after 6 weeks and over 6 months IPSSs were 8.34, 12.14, and 10.02, respectively. Urinary obstruction was reported in 14 cases (4.5%). Pretreatment IPSS (p = 0.003) and prostate volume (p = 0.024) were significantly associated with acute and late urinary toxicity. The dose for the most exposed 2 cc (D_2cc) of BN was not correlated with acute (p = 0.798) or late urinary toxicity (p = 0.859). BN D_2cc was not correlated with urinary obstruction (p = 0.272), but bladder V₇₅ was (p = 0.021).ConclusionsHigh pretreatment IPSS, large prostate volume and bladder V₇₅ were the only predictors of acute and late urinary toxicity after HDRB boost in our study. Although BN D_2cc was associated with acute and late urinary toxicity after low-dose-rate brachytherapy, no correlation was found after HDRB. A prospective study comparing dose to the BN in HDRB monotherapy would validate the impact of BN dose on acute and late urinary toxicity.     

Placement of empty catheters for an HDR-Emulating LDR Prostate Brachytherapy technique: Comparison to standard intraoperative planning

PurposeWe sought to determine whether placing empty catheters within the prostate and then inverse planning iodine-125 seed locations within those catheters (High Dose Rate-Emulating Low Dose Rate Prostate Brachytherapy [HELP] technique) would improve concordance between planned and achieved dosimetry compared with a standard intraoperative technique.Methods and MaterialsWe examined 30 consecutive low dose rate prostate cases performed by standard intraoperative technique of planning followed by needle placement/seed deposition and compared them to 30 consecutive low dose rate prostate cases performed by the HELP technique. The primary endpoint was concordance between planned percentage of the clinical target volume that receives at least 100% of the prescribed dose/dose that covers 90% of the volume of the clinical target volume (V₁₀₀/D₉₀) and the actual V₁₀₀/D₉₀ achieved at Postoperative Day 1.ResultsThe HELP technique had superior concordance between the planned target dosimetry and what was actually achieved at Day 1 and Day 30. Specifically, target D₉₀ at Day 1 was on average 33.7 Gy less than planned for the standard intraoperative technique but was only 10.5 Gy less than planned for the HELP technique (p < 0.001). Day 30 values were 16.6 Gy less vs. 2.2 Gy more than planned, respectively (p = 0.028). Day 1 target V₁₀₀ was 6.3% less than planned with standard vs. 2.8% less for HELP (p < 0.001). There was no significant difference between the urethral and rectal concordance (all p > 0.05).ConclusionsPlacing empty needles first and optimizing the plan to the known positions of the needles resulted in improved concordance between the planned and the achieved dosimetry to the target, possibly because of elimination of errors in needle placement.     

Shape analysis of the prostate: Establishing imaging specifications for the design of a transurethral imaging device for prostate brachytherapy guidance

PurposeTo examine specific prostate and urethra dimensions and prostate shape to facilitate the design of a transurethral ultrasonographic imaging device.Methods and MaterialsComputed tomographic (CT) data sets were retrospectively evaluated from 191 patients who underwent permanent prostate brachytherapy at our institution. The prostate, rectum, urethra, and bladder were each segmented with imaging software. Collected data and calculations included prostate volume at specific distances from the urethra and rectum, distances from seeds to urethra (SU), distances from seeds to rectum (SR), prostate length, and curvilinear prostatic urethra length.ResultsThe CT-based, postimplant mean prostate volume was 49 cm³ (range, 22–106 cm³). Mean prostate length was 4.5 cm (range, 3.1–6.0 cm). The mean curvilinear length of the prostatic urethra was 4.5 cm. The mean (standard deviation) prostatic urethra bend was 29.0° (12.2°). The mean surface distance from the prostate to the urethra was 2.9 cm and from the prostate to the rectum w as 4.6 cm (p < 0.001, paired t test). The mean SU distance was 1.6 cm, and the mean SR distance was 2.3 cm (p < 0.001). In the largest prostate, the mean SU distance was 3.9 cm and the mean SR distance was 6.0 cm.ConclusionsA urethral imaging device for prostate brachytherapy and other minimally invasive prostate therapies should ideally have a 6-cm imaging field of view to image all the prostates in this series in a single image. The mean distance from the SU in permanent prostate brachytherapy is less than 70% of the mean SR distance.     

Multivariate normal tissue complication probability modeling of vaginal late toxicity after brachytherapy for cervical cancer

PurposeTo explore the best variables combination for a predictive model of vaginal toxicity in cervical cancer patients undergoing brachytherapy (BT).Methods and MaterialsClinical and 3-dimensional dosimetric parameters were retrospectively extracted from an institutional database of consecutive patients undergoing intracavitary BT after external beam radiation therapy from 2006 to 2013 for a cervical cancer. A least absolute shrinkage and selection operator selection procedure in Cox's proportional hazards regression model was performed to select a set of relevant predictors for a multivariate normal tissue complication probability model of Grade ≥2 vaginal late toxicity. Outcomes reliability was internally assessed by bootstrap resampling method.ResultsOne hundred sixty-nine women were included in the present study with a median followup time of 3.8 years (interquartile range [IQR], 1.9–5.6 years). The 2 years and 5 years cumulative incidence rates of Grade ≥2 late vaginal toxicity were 19.9% and 27.5%, respectively. Among 31 metrics and six clinical factors extracted, the optimal model included two dosimetric variables: V70_Gy and D5_% (the percentage volume that received a dose greater or equal to 70 Gy and the minimum dose given to the hottest 5% volume, respectively). Area under the ROC curve at 2 and 5 years of followup were 0.85 and 0.91, respectively. Regarding internal validation, median area under the ROC curve of bootstrap predictions was 0.83 (IQR, 0.78–0.88) and 0.89 (IQR, 0.85–0.93) at 2 and 5 years of followup, respectively.ConclusionsA multivariate normal tissue complication probability model for severe vaginal toxicity based on two dosimetric variables (V70_Gy and D5_%) provides reliable discrimination capability in a cohort of cervical cancer treated with external beam radiation therapy and BT.     

Salvage low-dose-rate brachytherapy for local recurrences after prostatectomy and adjuvant or salvage external beam irradiation: Feasibility study on five patients and literature review

PurposeTo assess the feasibility and tumor outcome of re-irradiation with low-dose-rate brachytherapy for macroscopic local recurrences after radical prostatectomy (RP) followed by adjuvant or salvage external beam radiation therapy (EBRT).Methods and MaterialsBetween 2011 and 2018, five men with histologically proven local failure within the prostate (4) or seminal vesicle bed (1) after RP and adjuvant or salvage EBRT (median dose: 67.5 Gy) underwent a salvage brachytherapy (S-BT). The median delay after EBRT was 86 months (range 75–234). Two patients were castration-resistant at the time of S-BT. The gross tumor volume was defined on a multiparametric MRI and transrectal US imaging. Echo-guided transperineal implants of Iodine-125 seeds were optimized with a per-operative dosimetry and delivered with the seed-selectron.ResultsA high conformity was achieved with a high dose to the CTV (D_95% > 145 Gy in all but one) and very low dose to the rectum, urethra, and bladder. With a median followup of 21 months, all but one patient experienced nodes and/or bone metastases. Local control was achieved in 3/4 of evaluable patients (local failure distant to the treated volume in one). To date, no Grade 2 or more late toxicities were observed.ConclusionFor selected patients, focal local recurrence brachytherapy after PR and EBRT appears technically feasible and safe, but the efficacy remains uncertain as the majority of patients quickly relapsed at other sites. Large prospective studies are still required to better select patients who will benefit from this strategy.     

Patient-reported outcomes after Low-dose-rate versus High-dose-rate brachytherapy boost in combination with external beam radiation for intermediate and high risk prostate cancer

PURPOSEAddition of a brachytherapy boost to external beam radiation therapy (EBRT) reduces prostate cancer (PCa) recurrence at the expense of genitourinary (GU) toxicity. Whether brachytherapy boost technique, specifically low-dose-rate (LDR-BT) versus high-dose-rate (HDR-BT), impacts treatment-related toxicity is unclear.METHODSBetween 2012-2018, 106 men with intermediate/high risk PCa underwent EBRT (37.5-45 Gy in 1.8-2.5 Gy/fraction) plus brachytherapy boost, either with LDR-BT (110 Gy I-125 or 100 Gy Pd-103; n = 51) or HDR-BT (15 Gy x1 Ir-192; n = 55). Patient-reported outcomes (PRO) were assessed by International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC-CP) surveys at 3-6-month intervals for up to three years following treatment, with higher scores indicating more severe toxicity. Provider-reported GU and gastrointestinal (GI) toxicity was graded per CTCAE v5.0 at each follow-up. Linear mixed models comparing PROs between LDR-BT versus HDR-BT were fitted. Stepwise multivariable analysis (MVA) was performed to account for age, gland size, androgen deprivation therapy use, and alpha-blocker medication use. Incidence rates of grade 2+ GU/GI toxicity was compared using Fisher's exact test.RESULTSUse of LDR-BT was associated with greater change in IPSS (p=0.003) and EPIC-CP urinary irritative score (p = 0.002) compared with HDR-BT, but effect size diminished over time (LDR-BT versus HDR-BT: baseline to 6-/24-month mean IPSS change, +6.4/+1.4 versus +2.7/-3.0, respectively; mean EPIC-CP irritative/obstructive change, +2.5/+0.1 versus +0.9/+0.1, respectively). Results remained significant on MVA. Post-treatment grade 2+ GU toxicity was significantly higher in the LDR-BT group (67.5% versus 42.9% for LDR-BT and HDR-BT, respectively; p <0.001). There were no differences between groups in incontinence, bowel function, and erectile function, or grade 2+ GI toxicity.CONCLUSIONCompared with LDR-BT, HDR-BT was associated with lower acute patient- and provider-reported GU toxicity.     

High-dose-rate interstitial brachytherapy as monotherapy in one fraction and transperineal hyaluronic acid injection into the perirectal fat for the treatment of favorable stage prostate cancer: treatment description and preliminary results

PurposeTo evaluate the technical feasibility, acute and late genitourinary (GU) toxicity, and gastrointestinal toxicity after high-dose-rate (HDR) brachytherapy as monotherapy in one fraction with transperineal hyaluronic acid injection into the perirectal fat to displace the rectal wall away from the radiation sources to decrease rectal toxicity.Methods and MaterialsBetween April 2008 and January 2010, 40 consecutive patients were treated with favorable clinically localized prostate cancer; the median followup was 19 months (range, 8–32). No patients received external beam radiation, and 35% received hormone therapy before brachytherapy. All patients received one implant and one fraction of HDR. Fraction dose was 19 Gy. Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, Version 4.0.ResultsAll patients tolerated the implantation procedure very well with minimal discomfort. No intraoperative or perioperative complications occurred. Acute toxicity Grade 2 or more was not observed in any patients. No chronic toxicity has been observed after treatment. Logistic regression showed that the late Grade 1 GU toxicity was associated with D₉₀ (p = 0.050). The 32-month actuarial biochemical control was 100% and 88%, respectively (p = 0.06) for low- and intermediate-risk groups.ConclusionsThis is the first published report of the use of HDR brachytherapy as monotherapy in one fraction for patients with favorable-risk prostate cancer. This protocol is feasible and very well tolerated with low GU morbidity, no gastrointestinal toxicity, and the same level of low-dose-rate biochemical control at 32 months.