Supplemental External Beam Radiation Research Articles

Intraoperative Radiation Therapy Delivered by Brachytherapy in Breast Cancer: An Interim Analysis of a Phase 2 Trial

PurposeIntraoperative breast cancer radiotherapy (IORT) offers an alternative to external beam radiotherapy (EBRT) after breast-conserving surgery (BCS). The Intraoperative brachytherapy (IOBT) trial applies high dose rate (HDR) brachytherapy with a new applicator prototype as IORT after BCS. In this interim analysis of the IOBT trial, we present the oncological safety and toxicity of the method MethodsEligible patients were women, ≥ 50 years old with an unifocal nonlobular, estrogen-receptor-positive, HER2-negative breast cancer, cN0, ≤ 3 cm, treated with BCS and sentinel node biopsy (SNB). Toxicity was registered according to the LENT-SOMA scale. Cumulative incidence of local (LR) and regional recurrence (RR) were calculated through cumulative incidence function whereas overall survival (OS) was illustrated through Kaplan–Meier curve. ResultsUntil February 2023, 155 women (median age 68 years) were included in the trial. Twenty-nine women (18.7%) received supplemental EBRT, mostly due to positive SNB. Three-year cumulative incidence of LR and RR were 1.0% (CI 95 % 0.1%-2.3%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five- year cumulative incidence of LR and RR were 3.9% (CI 95% 1.8%-6.4%) and 2.1% (CI 95% 0.8%-4.2%) respectively. Five-year OS was 96.3% (CI 95% 93.6%-98.4%). Side effects were limited, low grade, and transient. ConclusionAcknowledging the short median follow-up time at interim analysis, our initial results indicate that delivering IORT through HDR brachytherapy in carefully selected breast cancer patients is feasible and oncological safe so far. A long-term follow-up is essential to confirm the initial results.

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old-Updated Results.

Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports updated outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. Between April 2006 and December 2022, 6,130 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator. Information was available for 4,143 patients. 3568 (86.12%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 575 (13.88%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 1,035 (24.98%) of these cases. The mean age was 67.4 years old. 48 patients were younger than 50 years old (mean age 46.6). 4,095 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 43.75%, 50.00%, 6.25% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 23.88%, 57.05%, 19.07% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 47.92%, 7 in 47.92%, and 8-10 in 4.16%. 44 younger patients were treated with SBRT alone. 4 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.42%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 29.84%, 7 in 54.14%, and 8-10 in 16.02%. 3522 were treated with SBRT alone. 573 patients also received supplemental external beam radiation (median dose 4500cGY) and 1030 patients (25.15%) received Androgen Deprivation Therapy (ADT) as part of their treatment. At 75 months the 6-year biochemical relapse free survival was 95.83% in younger patients compared to 98.41% in older patients using the Phoenix definition of biochemical failure. The 6-year median post treatment PSA was 0.3 in younger patients and 0.2 in the older patients. There were no significant differences in the risk stratification between the 2 groups. This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With updated 6-year follow up, SBRT remains an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Intra-Operative Radiotherapy (IORT) in Breast Conserving Therapy in Early-Stage Breast Cancer and DCIS

Initial breast intra-operative radiotherapy (IORT) results in clinical trials were encouraging though with longer follow up, increased local recurrences have been reported compared with whole breast radiation or other partial breast radiation including accelerated partial breast irradiation (APBI) methods. The goal of the study is to report our prospective single institution IORT breast study outcomes of local recurrence (LR) including true recurrence and breast elsewhere failures, breast cancer specific survival (BCSS), and overall survival (OS) with low energy x-ray IORT in early-stage breast cancer or ductal carcinoma in situ. A total of 480 patients with early-stage breast cancer or DCIS were prospectively enrolled in an IRB approved single institution trial and treated with low energy X-ray IORT 20 Gy at time of breast-conserving surgery. Eligibility criteria included ≥ 45 years of age with unifocal tumors < 3 cm deemed candidates for partial mastectomy. Supplemental external beam radiation was recommended for patients with high-risk surgical pathology including multifocal disease, positive nodes, close margins < 2 mm, or lymphovascular invasion. Ipsilateral breast tumor recurrences were classified as true recurrence versus elsewhere failure by location and histology: same/different quadrant and similar/different histology. Kaplan-Meier methods were used to estimate survival probabilities across time. Median age of enrolled patients was 64 years with the majority of patients having favorable phenotype with 94% ER+ and 93% Her-2 - disease. 110 patients (23%) had supplemental EBRT delivered; 103 to the whole breast and 7 to the breast and regional nodes. At a median follow up of 73 months (range 17 - 131 months), there were 23 (4.8%) ipsilateral breast tumor recurrences, of which 9 were true recurrences (1.9%) and 14 elsewhere failures (2.9%). One patient with true recurrence and 3 patients with elsewhere breast failures synchronously presented with clinical or radiographic regional node involvement. Seven patient developed contralateral breast cancer and 8 patients developed distant metastases during the follow-up period. There were 2 breast cancer related deaths. At 6-years, overall survival rate was 96.8% and breast cancer specific survival was 98.7%. Our study outcomes reflect similar outcomes as other reported IORT studies with electron or low energy X-ray in breast cancer, with higher risk of local failure than historical whole breast and other partial breast radiation techniques. This supports current radiation society guidelines for IORT monotherapy for breast cancer to be optimally considered in the context of prospective clinical trials.

Effect of Adequate Local Radiation Dose on Oncological Outcomes in Localized Prostate Cancer Patients Treated With Low-dose-rate Brachytherapy.

We retrospectively investigated the effect of a biologically effective dose (BED) of Low-dose rate brachytherapy (LDR-BT) and its possible interaction with androgen deprivation therapy (ADT) during LDR-BT treatment for intermediate-risk prostate cancer (PCa). A total of 693 patients with localized, intermediate-risk PCa, who underwent LDR-BT with or without supplemental external beam radiotherapy, were included in this study. We stratified patients into two groups according to BED (<180 Gy2, lower BED group; ≥180 Gy2, higher BED group) and evaluated the effect of ADT duration on the oncological outcomes of each group. In total, 431 patients received BED ≥180 Gy2. Significant differences in biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS) were observed among the non-ADT, ADT ≤3 months, and ADT >3 months subgroups of the lower BED group (p=0.005 and 0.049, respectively). However, no significant differences in BCRFS or CPFS were detected in the higher BED group (p=0.63 and 0.76, respectively). Multivariate analysis of BCR and CP in the lower BED group revealed a significant decreasing trend in the BCRFS (p for trend=0.001) and CPFS rates (p for trend=0.015) as ADT duration increased, which was associated with favorable outcomes. However, no significant trend was observed in the BCRFS or CPFS rate in the higher BED group. An adequate local radiation dose provides favorable oncological outcomes and could potentially reduce the need for long-term ADT.

Evaluation of dose perturbations around iodine-125 seed sources in supplemental external beam prostate radiotherapy.

We investigated dose perturbations caused by 125I seeds in patients undergoing supplemental external beam radiotherapy (EBRT) for prostate cancer. We examined two types of nonradioactive seed models: model 6711 and model STM1251. All experiments were performed using a water-equivalent phantom. Radiochromic film was used to measure the dose distributions adjacent to the seeds upstream and downstream of the external beam source. Single and clusters of multiple seeds were placed in slots in a solid water (SW) slab to measure dose perturbations with separate versus dense seed placement at beam energies of 6 or 10 MV. Monte Carlo simulations (MCSs) were also performed to include the theoretical basis against film dosimetry. Distinct patterns of dose enhancement (buildup [BU]) were upstream, and dose reduction (builddown [BD]) were downstream of the radiation source. Model 6711 with lower photon beam energies produced larger dose perturbations of BU and BD than the model STM1251. The results showed the same tendency with different seed placements and beam energies. However, these differences were not observed in the rotational irradiation measurement, which replicated a clinical plan. Dose perturbations around seeds result in dose enhancement and dose reduction with varying impact depending on the photon beam energy and seed type. This has the potential to cancel out these perturbations using multiple beam direction fields.

Biochemical outcomes and toxicities in young men with prostate cancer after permanent iodine-125 seed implantation: Prospective cohort study in 6662 patients

PURPOSEWe evaluated the effect of age, <60 and ≥60 years, on biochemical outcomes and toxicities in patients with prostate cancer who underwent permanent seed implantation (PI) ± external beam radiation therapy ± hormone therapy in a national Japanese prospective cohort study (J-POPS). METHODS AND MATERIALSThe safety and efficacy analyses included 6721 and 6662 patients, respectively. We categorized patients into two age groups: <60 (n = 716) and ≥60 (n = 6,005) years. We used propensity score matching (PSM) to estimate the marginal effect of age on biochemical freedom from failure (bFFF) using a Phoenix definition and Cox proportional hazard models. RESULTSThe median followup period was 60.0 months. Without PSM, men <60 years demonstrated similar 5-year bFFF (96.3%) compared with men ≥60 years (95.6%; p = 0.576); percent positive biopsies, biologically effective dose, Gleason score, risk classification, and supplemental external beam radiation therapy (p <0.001, <0.001, <0.001, 0.008, and <0.001) were significantly associated with bFFF while age was not (p = 0.576). With PSM, bFFF was not significantly different between age groups (p = 0.664); however, men <60 years showed a significantly lower incidence of declining erectile function, grade ≥2 all urinary toxicities, urinary frequency/urgency, and rectal bleeding (p <0.001, 0.024, 0.031, and 0.010) than men ≥60 years. CONCLUSIONSAfter PI, men <60 years achieved a comparable 5-year biochemical control rate and showed a lower incidence of several toxicities compared to men ≥60 years. This suggests that PI should be an excellent treatment option for men <60 years with prostate cancer.

Prognostic value of PSA bounce after definitive radiotherapy revisited.

Prostate-specific antigen (PSA) bounce after definitive radiotherapy has been reported as a predictor of improved biochemical recurrence-free survival (BCRFS). We revisited this phenomenon to confirm its clinical impact on oncological outcomes in patients with long-term follow-up who were free of biochemical recurrence (BCR) at least 3years after treatment. A total of 541 patients with localized, intermediate-risk prostate cancer underwent low-dose rate brachytherapy with iodine-125 seeds with or without supplemental external beam radiotherapy in combination. Neoadjuvant hormonal therapy was administered to 273 patients (50.5%) with a median duration of 3months (range 1-108months). PSA bounce was defined as ≥ 0.2ng/ml increase above the interval PSA nadir, followed by a decrease below that value. The median age was 69years (range 49-90years). The median follow-up duration was 102months (range 36-205months). One-hundred and fifty patients (27.7%) had PSA bounce with a median magnitude of 0.47ng/ml (range 0.2-3.19ng/ml). Age was significantly associated with the occurrence of PSA bounce [age: hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.93-0.98]. It was found to be independently associated with a decreased risk for BCR (HR 0.29; 95% CI 0.12-0.69) and clinical progression (HR 0.44; 95% CI 0.95-0.98). PSA bounce indicated a favorable BCRFS and clinical progression-free survival in patients who had been free of BCR for at least 3years after definitive radiotherapy.

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old

Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients.Between April 2006 and December 2020, 3626 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator and followed at an academic institution. 3173 (87.51%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 453 (12.49%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 865 (23.86%) of these cases. The mean age was 67.3 years old. 47 patients were younger than 50 years old (mean age 46.6). 3,579 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 44.68%, 48.94%, 6.38% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 24.76%, 56.83%, 18.41% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 48.94%, 7 in 46.81%, and 8-10 in 4.25%. 44 younger patients were treated with SBRT alone. 3 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.6%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 30.57%, 7 in 54.06%, and 8-10 in 15.37%. 3129 were treated with SBRT alone. 450 patients also received supplemental external beam radiation (median dose 4500cGY) and 860 patients (24.03%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen.At 64.8 months (range 7 months - 177 months) the 5-year biochemical relapse free survival was 98% in younger patients compared to 99% in older patients using the Phoenix definition of biochemical failure. The 5-year median post treatment PSA was 0.15 in the younger patients and 0.20 in the older patients. There were no significant differences in biochemical relapse free survival between the groups.This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With 5-year follow up, SBRT is an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

How long is long enough to secure disease control after low-dose-rate brachytherapy in combination with other modalities in intermediate-risk, localized prostate cancer?

Previous studies have demonstrated excellent overall outcomes in patients who underwent low-dose-rate brachytherapy (LDR-BT) in intermediate-risk, localized prostate cancer (PCa). We thus investigated the appropriate length of time before completing prostate-specific antigen (PSA) monitoring after treatment. Between 2003 and 2014, 710 localized, intermediate-risk PCa patients underwent LDR-BT with or without supplemental external beam radiotherapy (EBRT). Data from 567 of those patients was analyzed in this study. Neoadjuvant hormonal therapy (NHT) was administered to 315 patients (55.6 %) and NHT with adjuvant hormonal therapy (AHT) to 59 patients (10.4 %), as per the protocol of a prospective randomized controlled trial (SHIP0804). We stratified patients by posttreatment PSA levels at specific times and assessed the factors for association with biochemical recurrence (BCR) and for clinical progression (CP). The median follow-up was 109 months (range, 60-205 months). Of 529 patients who were BCR-free at 3 years after treatment, 56 subsequently developed BCR, and 47 developed CP. PSA at 3 and 5 years after treatment were significantly correlated with long-term oncological outcomes. No patients with 5-year PSA levels ≤0.1 ng/mL subsequently developed BCR or CP. Discontinuation of PSA monitoring could be discussed with patients with intermediate-risk PCa as a reasonable option if PSA levels remain ≤0.1 ng/mL at 5 years after LDR-BT, either alone or with other combined modalities, as subsequent recurrences are quite rare.

Influence of hydrogel spacer placement with prostate brachytherapy on rectal and urinary toxicity.

To determine the influence of rectal hydrogel spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low-dose-rate (LDR) brachytherapy, with or without supplemental external beam radiotherapy (EBRT). A total of 224 patients underwent LDR brachytherapy with HSP, as monotherapy or combined with EBRT, between January 2016 and December 2019. Dosimetric variables reflecting the extent of rectal sparing and late rectal toxicity outcomes were evaluated. This spacer cohort was retrospectively compared to a similar patient group (n = 139) in whom HSP was not used. Hydrogel spacer placement was associated with significantly reduced rectal doses for all dosimetric variables; the median percentage rectal dose to 1 cc of rectum and rectal dose to 2 cc of rectum of the spacer cohort were all significantly lower compared to the non-spacer cohort. The incidence rates of overall (any grade) and grade ≥2 rectal toxicity were lower in patients with HSP compared to patients who did not undergo HSP: 12% and 1.8% vs 31% and 5.8%, respectively. The 3-year cumulative incidence of overall rectal toxicity was significantly lower with HSP than without (15% vs 33%; P < 0.001), corresponding to an overall rectal toxicity reduction on univariable analysis (hazard ratio 0.45, 95% confidence interval 0.28-0.73; P = 0.001). In this patient cohort treated with prostate brachytherapy, none of the urethral dosimetric variables or the presence or absence of HSP was associated with late urinary toxicity. Hydrogel rectal spacer placement is a safe procedure, associated with significantly reduced rectal dose. HSP translates to a decrease in overall late rectal toxicity in patients receiving dose-escalated brachytherapy-based procedures.

New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer

BackgroundThe TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses.MethodsIn total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0–N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT.ResultsLocal recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt. Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17–0.88) P = 0.0091.ConclusionTARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect.Trial registrationISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

PP08 Presentation Time: 11:10 AM: Influence of Hydrogel Spacer Placement in Conjunction with Prostate Brachytherapy with or without External Beam Radiotherapy on Rectal Toxicity Outcomes

Purpose: This study aimed to determine the influence of hydrogel rectal spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low dose rate (LDR) brachytherapy with or without supplemental external beam radiotherapy (EBRT).

Effect of adding androgen deprivation therapy to permanent iodine-125 implantation with or without external beam radiation therapy on the outcomes in patients with intermediate-risk prostate cancer: A propensity score–matched analysis

PurposeThe purpose of the study was to evaluate the effect of adding androgen deprivation therapy (ADT) to brachytherapy with or without external beam radiation therapy on oncological outcomes in prostate cancer. Methods and MaterialsOverall, 1,171 patients with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy with or without ADT between 2003 and 2013 were identified. Propensity score matching was used to counter biases between the ADT and non-ADT groups. The biochemical failure-free rate (bFFR), local recurrence-free rate, and overall survival rate were evaluated using Kaplan–Meier curves, and predictors were identified using Cox proportional hazards regression models. ResultsAfter propensity score matching, 405 patients were included in each group. The median followup duration was 9.1 years; the median ADT duration was 6 months. In the ADT versus non-ADT groups, the 9-year bFFR, local recurrence-free rate, and overall survival rate were 93.4% versus 87.8% (p = 0.016), 96.9% versus 98.1% (p = 0.481), and 88.1% versus 90.4% (p = 0.969), respectively. On multivariate analyses, Gleason score (hazard ratio [HR]: 2.52, 95% confidence interval [CI]: 1.58–4.03) and ADT use (HR: 0.55, 95% CI: 0.34–0.89) were associated with biochemical failure. Supplemental external beam radiation therapy use (HR: 0.38, 95% CI: 0.16–0.91) was associated with lower local recurrence rates. Age (HR: 1.12, 95% CI: 1.08–1.16) and comorbidities (HR: 1.56, 95% CI: 1.04–2.34) were associated with all-cause mortality. ConclusionsA risk-benefit assessment between bFFR improvement and the potential side effects of adding ADT to brachytherapy-based radiotherapy is warranted before incorporating ADT as routine practice.

Targeted Intraoperative Radiotherapy Is Non-inferior to Conventional External Beam Radiotherapy in Chinese Patients With Breast Cancer: A Propensity Score Matching Study.

Purpose: To investigate the efficacy of targeted intraoperative radiotherapy (TARGIT) vs. conventional external beam radiotherapy (EBRT) in Chinese patients with breast cancer.Methods: We retrospectively analyzed breast cancer patients who underwent breast-conserving surgery (BCS) at our hospital between April 2009 and October 2017. Patients were divided into TARGIT group and EBRT group according to different radiotherapy methods. TARGIT was performed with low-energy X-rays emitted by the Intrabeam system to deliver a single dose of 20 Gy to the applicator surface. Propensity score matching was performed at 1:1. The Kaplan–Meier method was used to calculate the locoregional recurrence (LR), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) of the two groups, and the log-rank test was run to analyse between-group difference before and after matching.Results: A total of 281 patients were included, with a median follow-up of 43 months. Of them, 82 were included in the TARGIT group and 199 in the EBRT group. Using the risk-adapted approach, 6.1% of patients received supplemental EBRT in the TARGIT group. The 5-year LR rate was 3.2% in the TARGIT group and 3.1% in the EBRT group (P = 0.694), the 5-year DMFS rates were 100 and 96.7%, respectively (P = 0.157); the 5-year DFS rates were 96.8 and 94.2% (P = 0.604); and the 5-year OS rates were 97.6 and 97.8% (P = 0.862). After matching which eliminated interference from imbalanced baseline factors, 128 matched patients were analyzed by the Kaplan–Meier method. The 5-year LR rate was 2.3% in the TARGIT group and 1.6% in the EBRT group; the 5-year DMFS rates were 100 and 98.4%, respectively; the 5-year DFS rates were 97.7 and 98.4%; and the 5-year OS rates were 98.4 and 98.4% (P = 0.659, 0.313, 0.659, 0.987). There was no significant difference in efficacy between TARGIT group and EBRT group.Conclusion: TARGIT and EBRT have similar 5-year outcomes in selected Chinese breast cancer patients undergoing BCS, and it can be used as an effective alternative to standard therapy, with substantial benefits to patients. The results need to be further confirmed by extending the follow-up time.

Evaluation of the urethral α/β ratio and tissue repair half-time for iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy

PurposeTo assess the correlation between postimplant dosimetric quantifiers and the genitourinary (GU) toxicity of low-dose rate brachytherapy for prostate cancer. Methods and MaterialsThe minimum urethral dose (UD10, 30, and 90) and the percent volume of the urethra receiving the prescription dose (V100, V150) were calculated from the postimplant dose-volume histograms of 182 patients. We then calculated various urethral biologically equivalent doses (uBEDs) using different values of the α/β ratio and tissue repair half-time (t1/2) and examined the correlations with GU toxicity. ResultsCommon dosimetric quantifiers, such as UD90 (brachytherapy) + UD50 (external beam radiotherapy), showed no correlation with Grade ≥ 2 GU toxicity. There was a significant correlation between Grade ≥2 GU toxicity and uBED when the α/β value was 0.5 or 1 Gy and t1/2 was 0.5–2.5 h. An uBED (α/β = 1.0, t1/2 = 0.5) had the largest hazard ratio for GU toxicity, and it was also significantly correlated with Grade ≥ 2 GU toxicity according to multivariate analysis. ConclusionsWe observed a significant correlation of uBED with GU toxicity when α/β was 0.5 or 1.0 Gy and t1/2 was 0.5–2.5 h. As the simple formula we used has not been verified in basic experiments, more data are needed to validate our results.

EDITORIAL COMMENT

The authors are to be congratulated for their work exploring low-dose rate (LDR) brachytherapy for prostate cancer. It is a modality that gets much less attention than it deserves as the authors’ findings indicate. They do an excellent job discussing the shortcomings of their research but they could add to the corroborating evidence that strengthens their findings. In particular their musings about the lack of benefit of androgen deprivation therapy (ADT) in their LDR patients. I think that they are correct that the higher dose of LDR may obviate the need for ADT in intermediate-risk patients. They discuss the lack of value of ADT in intermediate-risk patients well; however, there are 2 other papers in high-risk patients that also support this contention. 1 Ciezki JP Weller M Reddy CA et al. A comparison between low-dose-rate brachytherapy with or without androgen deprivation, external beam radiotherapy with or without androgen deprivation, and radical prostatectomy with or without adjuvan or salvage radiation therapy for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2017; 97: 962-975 Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar ,2 Yang DD Muralidhar V Nguyen PL et al. Lack of benefit from the addition of external beam radiation therapy to brachytherapy for intermediate- and high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2017; 99: 904-911 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar In both papers, no positive effect from adding ADT to LDR was noted. It is significant that the single-institutional findings 1 Ciezki JP Weller M Reddy CA et al. A comparison between low-dose-rate brachytherapy with or without androgen deprivation, external beam radiotherapy with or without androgen deprivation, and radical prostatectomy with or without adjuvan or salvage radiation therapy for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2017; 97: 962-975 Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar are corroborated by data from SEER (Surveillance, Epidemiology, and End Results). 2 Yang DD Muralidhar V Nguyen PL et al. Lack of benefit from the addition of external beam radiation therapy to brachytherapy for intermediate- and high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2017; 99: 904-911 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar While there are multiple sources of level 1 evidence supporting the use of ADT in high-risk prostate cancer patients treated with external beam radiation therapy (EBRT), no such level 1 evidence exists for brachytherapy in any risk category. It is reasonable to conclude that if ADT is not known to improve efficacy in high-risk patients treated with LDR, then it is unlikely to have efficacy benefits in intermediate-risk patients. Additionally, the authors’ note the lack of benefit for supplemental EBRT in their series, but the numbers are too small to make firm conclusions. While this paper does not meaningfully add to the evidence that EBRT is not necessary in patients treated with LDR, the same papers that support the lack of benefit of ADT also support the omission of EBRT from other risk groups of prostate cancer patients treated with LDR.

Toxicity and risk factors after combined high-dose-rate brachytherapy and external beam radiation therapy in men ≥75years with localized prostate cancer.

Combined high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) is afavorable treatment option in non-metastatic prostate cancer. However, reports on toxicity and outcome have mainly focused on younger patients. We aimed to determine toxicity and biochemical control rates after combined HDR-BT and EBRT in men ≥75years. From 1999 to 2015, 134 patients aged ≥75years (median 76years; 75-82years) were identified. Patients received 18 Gy of HDR-BT (9 Gy/fraction on days1 and8) with an iridium-192 source. After 1week, supplemental EBRT with atarget dose of 50.4 Gy was started (delivered in 1.8 Gy fractions). Median follow-up time was 25months (0-127months). No severe (grade4) gastrointestinal (GIT) or genitourinary (GUT) toxicities were observed. In 76patients (56.7%), 3D conformal radiation therapy (CRT) and in 34.3% intensity-modulated radiotherapy (IMRT) was applied. CRT-treated patients were at a2.17-times higher risk (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.31-3.57, p = 0.002) of experiencing GUT. GIT risks could be reduced by 78% using IMRT (HR: 0.22, 95% CI: 0.07-0.75, p = 0.015). Patients with ahigher Tstage (T2c-3a/b) were less likely to experience GIT or GUT (HR: 0.49, 95% CI: 0.29-0.85, p = 0.011 and HR: 0.5, 95% CI: 0.3-0.81, p = 0.005, respectively). HDR-BT/EBRT is awell-tolerated treatment option for elderly men ≥75years with alimited number of comorbidities and localized intermediate- or high-risk prostate cancer. IMRT should be favored since side effects were significantly reduced in IMRT-treated patients.

Comparison of LDR Brachytherapy Combined with Conventionally Fractionated EBRT or SBRT in High Risk Node Negative Prostate Cancer Patients: Early Toxicity and Tumor Control Outcomes

One of the most effective radiotherapeutic interventions for the treatment of high-risk prostate is the combination of brachytherapy with supplemental external beam radiotherapy directed to the prostate and regional nodes. While conventionally fractionated external beam radiotherapy has been a standard approach to supplement the brachytherapy boost, we have recently treated such patients with supplemental SBRT using an ultra-hypofractionated regimen. In this study we compare the early toxicity and tumor control outcomes of high risk, node negative patients treated with combination of brachytherapy and SBRT versus brachytherapy and conventionally fractionation RT (CFRT).

Predictive factors of long-term rectal toxicity following permanent iodine-125 prostate brachytherapy with or without supplemental external beam radiation therapy in 2216 patients

PurposeWe analyzed factors associated with rectal toxicity after iodine-125 prostate brachytherapy (BT) with or without external beam radiation therapy (EBRT). Methods and MaterialsIn total, 2216 prostate cancer patients underwent iodine-125 BT with or without EBRT between 2003 and 2013. The median followup was 6.9 years. Cox proportional hazards modeling was used for univariate and multivariate analyses to assess clinical and dosimetric factors associated with rectal toxicity. Dosimetric parameters from 1 day after implantation (Day 1) and 1 month after implantation (Day 30) were included in the analyses. ResultsThe 7-year cumulative incidence of Grade 2 or higher rectal toxicity was 5.7% in all patients. The multivariate analysis revealed that antiplatelet or anticoagulant therapy, neoadjuvant androgen deprivation therapy, treatment modality, Day 1 rectal volume receiving 100% of the prescribed dose (RV100), and the Day 30 minimal percent of the prescribed dose delivered to 30% of the rectum (RD30) were associated with rectal toxicity. Day 1 RV100 was a common predictor in both BT-alone and the BT + EBRT groups. The 5-year cumulative incidence of Grade 2 or higher rectal toxicity was 12.6%, 5.9%, and 1.7% for BT + 3-dimensional conformal radiation therapy, BT + intensity-modulated radiation therapy, and the BT-alone groups, respectively (p < 0.001). ConclusionsRectal dosimetric parameters in BT were associated with late rectal toxicity. Although the risk of rectal toxicity was higher when EBRT was combined with BT, with proper and achievable rectal dose constraints intensity-modulated radiation therapy yielded less toxicity than 3-dimensional conformal radiation therapy.

Low dose rate prostate brachytherapy.

Low dose rate (LDR) prostate brachytherapy is an evidence based radiation technique with excellent oncologic outcomes. By utilizing direct image guidance for radioactive source placement, LDR brachytherapy provides superior radiation dose escalation and conformality compared to external beam radiation therapy (EBRT). With this level of precision, late grade 3 or 4 genitourinary or gastrointestinal toxicity rates are typically between 1% and 4%. Furthermore, when performed as a same day surgical procedure, this technique provides a cost effective and convenient strategy. A large body of literature with robust follow-up has led multiple expert consensus groups to endorse the use of LDR brachytherapy as an appropriate management option for all risk groups of non-metastatic prostate cancer. LDR brachytherapy is often effective when delivered as a monotherapy, although for some patients with intermediate or high-risk disease, optimal outcome are achieved in combination with supplemental EBRT and/or androgen deprivation therapy (ADT). In addition to reviewing technical aspects and reported clinical outcomes of LDR prostate brachytherapy, this article will focus on the considerations related to appropriate patient selection and other aspects of its use in the treatment of prostate cancer.