A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer.

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain. OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT. EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs). EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p < 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs. CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control. PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.

Non-operative management involving chemoradiation therapy combined with high-dose-rate brachytherapy for T3 rectal cancer using a vaginal shielded cylindrical applicator: a technical report.

It has been shown that a group of rectal cancer patients will achieve a pathological complete response following preoperative chemoradiotherapy, and non-operative management has recently gained attention. To escalate the tumour dose and increase the likelihood of pathological complete response, brachytherapy can play an important role in safely increasing the total dose. However, at the time this report was published, an applicator dedicated to rectal brachytherapy was unaffordable in Japan. Here, we report two T3 rectal cancer patients who were inoperable or refused surgery and treated by chemoradiotherapy following intracavitary brachytherapy involving a vaginal cylinder applicator with lead shielding.

Brachytherapy boost improves survival and decreases risk of developing distant metastases compared to external beam radiotherapy alone in intermediate and high risk group prostate cancer patients.

BACKGROUND AND PURPOSE: Despite several prospective trials showing a clinical benefit of combining external beam radiotherapy (EBRT) with brachytherapy boost (BTB) for the treatment of intermediate- and high-risk prostate cancer (PCa) patients, none of these trials was designed to test for a survival difference. In this study, we aimed to collect a large multi-institutional database to determine whether BT boost was associated with a statistically significant improvement in survival and a reduction of distant metastases based on real-world data. MATERIAL AND METHODS: We collected the data of patients treated for intermediate- or high-risk PCa with definitive EBRT or BTB, with or without androgen deprivation therapy (ADT), between January 2003 and December 2014 at two tertiary institutions. The statistical endpoints included overall survival (OS), freedom from distant metastases (FFDM), and metastases-free survival (MFS). The impact of treatment modality was assessed using Cox regression models and log-rank testing after one-to-one propensity score matching. RESULTS: A total of 1641 patients treated with EBRT (n = 1148) or high-dose-rate BTB (n = 493) were analyzed. The median survival and clinical follow-up were 117.8 (IQR 78-143.3) and 60.7 months, respectively. The radiotherapy modality (BTB) remained an independent prognostic factor for OS (HR 0.75; 95% CI 0.63-0.88; p < 0.001), FFDM (HR 0.54; 95% CI 0.4-0.73; p < 0.001), and MFS (HR 0.72; 95% CI 0.61-0.85; p < 0.001). After propensity score matching, the remaining 986 patients were well-balanced in terms of age, maximum PSA, ISUP grade group, and TNM T stage. OS (p < 0.001), FFDM (p = 0.001) and MFS (p < 0.001) were significantly higher in the BTB group. CONCLUSIONS: There is a strong positive association between BTB and OS, FFDM, and MFS in PCa patients treated with definitive RT for intermediate- or high-risk PCa.

Association of Brachytherapy Boost with Overall Survival for Gleason 9-10 Prostate Cancer: The Impact of Primary versus Secondary Pattern 5.

PURPOSE: The addition of a brachytherapy (BT) boost to external beam radiotherapy (EBRT) reduces recurrence risk in men with high-risk prostate cancer (PCa) and may reduce PCa-mortality for Gleason grade group 5 (GG5). Whether the extent of pattern five, a risk factor for distant metastases, impacts the benefit of a BT boost is unclear. METHODS: Men with localized GG5 PCa treated with (1) EBRT or (2) EBRT+BT between 2010 and 2016 were identified in the National Cancer Database. EBRT monotherapy group received conventionally fractionated (1.8-2.0 Gy per fraction) ≥74 Gy or moderately hypofractionated (2.5-3.0 Gy per fraction) ≥60 Gy. EBRT + BT group received conventionally fractionated ≥45 Gy or moderately hypofractionated ≥37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT; none received chemotherapy, immunotherapy, or surgery. OS was compared using Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards in the overall cohort, followed by subgroups based on primary versus secondary pattern 5. Propensity score- and exact-matching was used to corroborate results. RESULTS: A total of 8260 men were eligible: EBRT alone (89%) versus EBRT + BT (11%). 5-year OS for EBRT versus EBRT + BT was 76.3% and 85.0%, respectively (p = 0.002; multivariable adjusted HR 0.84, 95% CI 0.65-0.98; p = 0.04). These results remained consistent after propensity score and exact matching. The OS advantage of a BT boost was more prominent in men with Gleason 4 + 5 PCa (p = 0.001) and not observed in men with Gleason 5 + 5 or 5 + 4 PCa. CONCLUSIONS: Extent of pattern five may be useful in appropriately selecting men for EBRT+BT and should be considered as a pre-randomization stratification variable for future clinical trial design.

Does brachytherapy boost improve survival outcomes in Gleason Grade Group 5 patients treated with external beam radiotherapy and androgen deprivation therapy? A systematic review and meta-analysis.

Background: Localized Gleason Grade Group 5 (GG5) prostate cancer has a poor prognosis and is associated with a higher risk of treatment failure, metastases, and death. Treatment intensification with the addition of a brachytherapy (BT) boost to external beam radiation (EBRT) maximizes local control, which may translate into improved survival outcomes. Methods: A systematic review and meta-analysis was performed to compare survival outcomes for Gleason GG5 patients treated with androgen deprivation therapy (ADT) and either EBRT or EBRT + BT. The MEDLINE (PubMed), EMBASE and Cochrane databases were searched to identify relevant studies. Survival probabilities for distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were extracted and pooled to create a summary survival curve for each treatment modality, which were then compared at fixed points in time. An additional analysis was performed among studies directly comparing EBRT and EBRT + BT using a random-effects model. Results: Eight retrospective studies were selected for inclusion, representing a total of 1393 EBRT patients and 877 EBRT + BT patients. EBRT + BT was associated with higher DMFS starting at 6 years (86.8 % vs 78.8 %; p = 0.018) and extending out to 10 years (81.8 % vs 66.1 %; p < 0.001), with an overall hazard ratio of 0.53 (p = 0.02). There was no difference in PCSS or OS between treatment modalities. Differences in toxicity were not assessed. There was a wide range of heterogeneity between studies. Conclusion: The addition of BT boost is associated with improved long-term DMFS in Gleason GG5 prostate cancer, but its impact on PCSS and OS remains unclear. These results may be confounded by the heterogeneity across study populations with concern for a risk of bias. Therefore, prospective studies are necessary to further elucidate the survival advantage associated with BT boost, which must ultimately be weighed against the toxicity-related implications of this treatment strategy.

Technical report: a high-dose-rate interstitial brachytherapy boost for residual sinonasal undifferentiated carcinoma.

Sinonasal undifferentiated carcinoma (SNUC) is a highly aggressive and uncommon neoplasm that arises from the mucosa of the nasal cavity or paranasal sinuses. The multidisciplinary approach that includes surgery, radiation therapy (RT), and chemotherapy has been proven to improve survival rates. However, there is no established evidence for the efficacy of further (boost) irradiation following definitive RT in SNUC patients with residual primary tumor. We describe a successful case of a patient with SNUC who had an uncontrolled primary tumor following induction chemotherapy and radical concurrent chemoradiotherapy (CCRT) and underwent a high-dose-rate interstitial brachytherapy (HDR-ISBT) boost. A 75-year-old Japanese woman with unresectable locally advanced SNUC (LA-SNUC) received induction chemotherapy followed by radical CCRT. However, because the residual primary tumor was evident after planned external beam RT, she underwent an HDR-ISBT boost, and the tumor decreased significantly. A complete response (the Response Evaluation Criteria in Solid Tumors, ver. 1.1) was achieved 2 months after brachytherapy, and the patient has been disease-free for 2 years following treatment initiation. In conclusion, an HDR-ISBT boost can be a safe and effective treatment option in patients with residual and inoperable LA-SNUC in the maxillary sinus after initial RT.

Integrating external beam and prostate seed implant dosimetry for intermediate and high-risk prostate cancer using biologically effective dose: Impact of image registration technique.

PURPOSE: Combining external beam radiation therapy (EBRT) and prostate seed implant (PSI) is efficacious in treating intermediate- and high-risk prostate cancer at the cost of increased genitourinary toxicity. Accurate combined dosimetry remains elusive due to lack of registration between treatment plans and different biological effect. The current work proposes a method to convert physical dose to biological effective dose (BED) and spatially register the dose distributions for more accurate combined dosimetry. METHODS AND MATERIALS: A PSI phantom was CT scanned with and without seeds under rigid and deformed transformations. The resulting CTs were registered using image-based rigid registration (RI), fiducial-based rigid registration (RF), or b-spline deformable image registration (DIR) to determine which was most accurate. Physical EBRT and PSI dose distributions from a sample of 91 previously-treated combined-modality prostate cancer patients were converted to BED and registered using RI, RF, and DIR. Forty-eight (48) previously-treated patients whose PSI occurred before EBRT were included as a "control" group due to inherent registration. Dose-volume histogram (DVH) parameters were compared for RI, RF, DIR, DICOM, and scalar addition of DVH parameters using ANOVA or independent Student's t tests (α = 0.05). RESULTS: In the phantom study, DIR was the most accurate registration algorithm, especially in the case of deformation. In the patient study, dosimetry from RI was significantly different than the other registration algorithms, including the control group. Dosimetry from RF and DIR were not significantly different from the control group or each other. CONCLUSIONS: Combined dosimetry with BED and image registration is feasible. Future work will utilize this method to correlate dosimetry with clinical outcomes.

Role of Brachytherapy Boost in Clinically Localized Intermediate and High-Risk Prostate Cancer: Lack of Benefit in Patients with Very High-Risk Factors T3b-4 and/or Gleason 9-10.

This study examined the role of brachytherapy boost (BT-boost) and external beam radiotherapy (EBRT) in intermediate- to high-risk prostate cancer, especially in patients with very high-risk factors (VHR: T3b-4 or Gleason score 9-10) as patients with double very high-risk factors (VHR-2: T3b-4 and Gleason score 9-10) previously showed worst prognosis in localized prostate cancer. We retrospectively reviewed multi-institutional data of 1961 patients that were administered radiotherapy (1091 BT-boost and 872 EBRT: 593 conventional-dose RT (Conv RT: equivalent to doses of 2 Gy per fraction = EQD2 ≤ 72 Gy) and 216 dose-escalating RT (DeRT = EQD2 ≥ 74 Gy). We found that BT-boost improved PSA control and provided an equivalent overall survival rate in the intermediate- and high-risk groups, except for patients within the VHR factor group. In the VHR-1 group (single VHR), BT-boost showed a superior biochemical control rate to the Conv RT group but not to the DeRT group. In the VHR-2 group, BT-boost did not improve outcomes of either Conv RT or DeRT groups. In conclusion, BT-boost showed no benefit to modern DeRT in the patients with VHR; therefore, they are not good candidates for BT-boost to improve outcome and may be amenable to clinical trials using multimodal intensified systemic treatments.

Propensity score-matched analysis comparing dose-escalated intensity-modulated radiation therapy versus external beam radiation therapy plus high-dose-rate brachytherapy for localized prostate cancer.

PURPOSE: Dose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost. METHODS: From 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (DMean). Combined treatment was delivered as 46 Gy (DMean) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D90%). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0). RESULTS: The estimated 10-year bRFS was 82.0% vs. 76.4% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9% vs. 87.0% (p = 0.195) and the 10-year OS was 65.7% vs. 68.9% (p = 0.303), respectively. Cumulative 5­year late GU ≥ grade 2 toxicities were seen in 23.6% vs. 19.2% (p = 0.086) and 5­year late GI ≥ grade 2 toxicities in 11.1% vs. 5.0% of the patients (p = 0.002); cumulative 5­year late grade 3 GU toxicity occurred in 4.2% vs. 3.6% (p = 0.401) and GI toxicity in 1.0% vs. 0.3% (p = 0.249), respectively. CONCLUSION: Both treatment groups showed excellent long-term outcomes with low rates of severe toxicity.

The Role of Interstitial Brachytherapy for Breast Cancer Treatment: An Overview of Indications, Applications, and Technical Notes.

Breast cancer represents the second leading cause of cancer-related death in the female population, despite continuing advances in treatment options that have significantly accelerated in recent years. Conservative treatments have radically changed the concept of healing, also focusing on the psychological aspect of oncological treatments. In this scenario, radiotherapy plays a key role. Brachytherapy is an extremely versatile radiation technique that can be used in various settings for breast cancer treatment. Although it is invasive, technically complex, and requires a long learning curve, the dosimetric advantages and sparing of organs at risk are unequivocal. Literature data support muticatheter interstitial brachytherapy as the only method with strong scientific evidence to perform partial breast irradiation and reirradiation after previous conservative surgery and external beam radiotherapy, with longer follow-up than new, emerging radiation techniques, whose effectiveness is proven by over 20 years of experience. The aim of our work is to provide a comprehensive view of the use of interstitial brachytherapy to perform breast lumpectomy boost, breast-conserving accelerated partial breast irradiation, and salvage reirradiation for ipsilateral breast recurrence, with particular focus on the implant description, limits, and advantages of the technique.

Comparing Iridium-192 with Cobalt-60 sources in high-dose-rate brachytherapy boost for localized prostate cancer.

BACKGROUND: Dosimetric and clinical comparison of two cohorts of Iridium-192 (Ir-192) and Cobalt-60 (Co-60) high-dose-rate brachytherapy (DR-BT) boost for localized prostate cancer. MATERIAL AND METHODS: Patients with localized prostate cancer receiving either Ir-192 or Co-60 high-dose-rate brachytherapy (HDR-BT) boost in combination with external beam radiotherapy (EBRT) in the period of 2002-2019 were evaluated for dosimetric differences, side effects, biochemical relapse-free survival (bRFS), metastasis-free survival (MFS), and overall survival (OS). EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90%) 2 and 4 weeks after EBRT. Genitourinary (GU)/gastrointestinal (GI) toxicity were evaluated utilizing the Common Toxicity Criteria for Adverse Events version 5.0 and biochemical failure was defined according to the Phoenix definition. RESULTS: A total of 338 patients with a median follow-up of 101.8 (IQR 65.7-143.0) months were evaluated. At 10 years the estimated bRFS, MFS, and OS in our patient sample were 81.1%/71.2% (p=.073), 87.0%/85.7% (p=.862), and 70.1%/69.7% (p=.998) for Ir-192/Co-60, respectively. Cumulative 5-year late grade ≥2 GU toxicity was 20% for Ir-192 and 18.3% for Co-60 (p=.771). Cumulative 5-year late grade ≥2 GI toxicity was 5.8% for Ir-192 and 4.6% for Co-60 (p=.610). Grade 3 late GU side effects were pronounced in the Ir-192 cohort with 8.1% versus 1.4% in the Co-60 cohort (p=.01), which was associated with significantly lower dose to the organs at risk in the Co-60 cohort. PTV D90% was 9.3 ± 0.8 Gy versus 9.0 ± 1.1 Gy (p=.027) for Ir-192 versus Co-60. PTV V100% and PTV V150% were not significantly different between both cohorts. CONCLUSION: Co-60 brachytherapy sources are an effective alternative to Ir-192 in combined prostate HDR-BT boost + EBRT.

Elective nodal ultra hypofractionated radiation for prostate cancer: Safety and efficacy from four prospective clinical trials.

BACKGROUND AND PURPOSE: The role of elective nodal irradiation (ENI) in localized prostate cancer (PCa) is controversial. With increasing use of SBRT to the prostate, data is needed regarding the safety and efficacy of ENI using ultra-hypofractionated radiation (UHRT). MATERIALS AND METHODS: Between 2013-2020, 4 prospective clinical trials of intermediate or high-risk PCa receiving dose-escalated RT to the prostate (via HDR brachytherapy or SBRT boost) and ENI using UHRT (25 Gy in 5 weekly fractions) were conducted. Primary endpoints included acute genitourinary and gastrointestinal toxicities (CTCAE v3.0/4.0), and secondary endpoints included late genitourinary and gastrointestinal toxicities, patient-reported quality of life (EPIC) and biochemical failure (Phoenix definition). RESULTS: One-hundred sixty-five patients were enrolled, of whom 98 (59%) had high-risk disease. ADT was used in 141 (85%). Median follow-up was 38 months (IQR 10-63). The worst acute genitourinary and gastrointestinal toxicities respectively were 48% and 7.5% for grade 2, and 2.7% and 0% for grade 3. Cumulative incidence of late grade 2+ genitourinary and gastrointestinal toxicities at 36 months were 58% and 11.3% and for late grade 3+ toxicities were 1% and 0%, respectively. No grade 4+ acute or late toxicities were observed. Bowel and sexual toxicity significantly worsened up to 1-year compared to baseline. Over time, urinary (p < 0.0001), bowel (p = 0.0018) and sexual (p < 0.0001) scores significantly improved. The 3-year biochemical recurrence-free survival was 98%. CONCLUSION: ENI using UHRT is associated with low incidence of grade 3+ toxicity, while grade 1-2 acute genitourinary and gastrointestinal toxicity is common. Randomized phase 3 trials are needed.

Radiobiological comparison between Cobalt-60 and Iridium-192 high-dose-rate brachytherapy sources: Part I-cervical cancer.

PURPOSE: This study aimed to compare the biological effective doses (BEDs) to clinical target volume (CTV) and organs at risk (OARs) for cervical cancer patients treated with high-dose-rate (HDR) Iridium-192 (192 Ir) or Cobalt-60 (60 Co) brachytherapy (BT) boost and to determine if the radiobiological differences between the two isotopes are clinically relevant. METHODS: Considering all radiosensitivity parameters and their reported variations, the BEDs to CTV and OARs during HDR 60 Co/192 Ir BT boost were evaluated at the voxel level. The anatomical differences between individuals were also taken into account by retrospectively considering 25 cervical cancer patients. The intrafraction repair, proliferation, hypoxia-induced radiosensitivity heterogeneity, relative biological effectiveness (RBE), and source aging dose-rate variation were also taken into account. The comparisons in CTV were performed based on equivalent uniform BED (EUBED). RESULTS: Considering nominal parameters with no RBE correction, the CTV EUBEDs were almost similar with a median ratio of ∼1.00 (p < 0.00001), whereas RBE correction resulted in 3.9%-5.5% (p = 0.005, median = 4.8%) decrease for 60 Co with respect to 192 Ir. For OARs, the median values of D2cc (in EQD23 ) for 60 Co were lower than that of 192 Ir up to 9.2% and 11.3% (p < 0.00001) for nominal parameters and fast repair conditions, respectively. In addition, for a nominal value (reported range) of radiosensitive parameters, the CTV EUBED differences of up to 6% (5%-10%) were assessed for HDR-BT component. CONCLUSION: The RBE values are the most important cause of discrepancies between the two sources. By comparing BED/EUBEDs to CTV and OARs between 60 Co and 192 Ir sources, this numerical study suggests that a dose escalation to ∼4% is feasible and safe while sparing well the surrounding normal tissues. This 4% dose escalation should be benchmarked with clinical evidences (such as the results of clinical trials) before it can be used in clinical practice.

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.

PURPOSE: Addition 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. METHODS: Between 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. RESULTS: Use 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. CONCLUSION: Compared with LDR-BT, HDR-BT was associated with lower acute patient- and provider-reported GU toxicity.

Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer.

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p < 0.001) and PCSM (p < 0.001). These data suggest that radiorecurrent HRPCa has an aggressive natural history and that DM is clinically evident early after BCR. These findings underscore the importance of further investigations into upfront risk assessment and prompt systemic evaluation upon recurrence in HRPCa. PATIENT SUMMARY: High-risk prostate cancer that recurs after radiation therapy is an aggressive disease entity and spreads to other parts of the body (metastases). Some 60% of metastases occur within 1 yr. Approximately 30% of these patients die from their prostate cancer.

Five-year outcomes from a prospective comparative effectiveness study evaluating external-beam radiotherapy with or without low-dose-rate brachytherapy boost for localized prostate cancer.

BACKGROUND: To inform patients who are in the process of selecting prostate cancer treatment, the authors compared disease-specific function after external-beam radiotherapy (EBRT) alone versus EBRT plus a low-dose-rate (LDR) brachytherapy boost (EBRT-LDR). METHODS: For this prospective study, men who had localized prostate cancer in 2011 and 2012 were enrolled. Assessments at baseline, 0.5, 1, 3, and 5 years included the patient-reported Expanded Prostate Index Composite, the 36-item Medical Outcomes Study Short-Form Health Survey, and treatment-related regret. Regression models were adjusted for baseline function and for patient and treatment characteristics. The minimum clinically important difference in scores on the Expanded Prostate Index Composite 26-item instrument was from 5 to 7 for urinary irritation and from 4 to 6 for bowel function. RESULTS: Six-hundred ninety-five men met inclusion criteria and received either EBRT (n = 583) or EBRT-LDR (n = 112). Patients in the EBRT-LDR group were younger (median age, 66 years [interquartile range [IQR], 60-71 years] vs 69 years [IQR, 64-74 years]; P < .001), were less likely to receive pelvic radiotherapy (10% vs 18%; P = .040), and had higher baseline 36-item Medical Outcomes Study Short-Form Health Survey physical function scores (median score, 95 [IQR, 86-100] vs 90 [IQR, 70-100]; P < .001). Over a 3-year period, compared with EBRT, EBRT-LDR was associated with worse urinary irritative scores (adjusted mean difference at 3 years, -5.4; 95% CI, -9.3, -1.6) and bowel function scores (-4.1; 95% CI, -7.6, -0.5). The differences were no longer clinically meaningful at 5 years (difference in urinary irritative scores: -4.5; 95% CI, -8.4, -0.5; difference in bowel function scores: -2.1; 95% CI, -5.7, -1.4). However, men who received EBRT-LDR were more likely to report moderate or big problems with urinary function bother (adjusted odds ratio, 3.5; 95% CI, 1.5-8.2) and frequent urination (adjusted odds ratio, 2.6; 95% CI, 1.2-5.6) through 5 years. There were no differences in survival or treatment-related regret between treatment groups. CONCLUSIONS: Compared with EBRT alone, EBRT-LDR was associated with clinically meaningful worse urinary irritative and bowel function over 3 years after treatment and more urinary bother at 5 years. LAY SUMMARY: In men with prostate cancer who received external-beam radiation therapy (EBRT) with or without a brachytherapy boost (EBRT-LDR), EBRT-LDR was associated with clinically worse urinary irritation and bowel function through 3 years but resolved after 5 years. Men who received EBRT-LDR continued to report moderate-to-big problems with urinary function bother and frequent urination through 5 years. There was no difference in treatment-related regret or survival between patients who received EBRT and those who received EBRT-LDR. These intermediate-term estimates of function may facilitate counseling for men who are selecting treatment.

Brachytherapy boost (BT-boost) or stereotactic body radiation therapy boost (SBRT-boost) for high-risk prostate cancer (HR-PCa).

Systematic review for the treatment of high-risk prostate cancer (HR-PCa, D'Amico classification risk system) with external body radiation therapy (EBRT)+brachytherapy-boost (BT-boost) or with EBRT+stereotactic body RT-boost (SBRT-boost). In March 2020, 391 English citations on PubMed matched with search terms "high risk prostate cancer boost". Respectively 9 and 48 prospective and retrospective studies were on BT-boost and 7 retrospective studies were on SBRT-boost. Two SBRT-boost trials were prospective. Only one study (ASCENDE-RT) directly compared the gold standard treatment [dose-escalation (DE)-EBRT+androgen deprivation treatment (ADT)] versus EBRT+ADT+BT-boost. Biochemical control rates at 9 years were 83% in the experimental arm versus 63% in the standard arm. Cumulative incidence of late grade 3 urinary toxicity in the experimental arm and in the standard arm was respectively 18% and 5%. Two recent studies with HR-PCa (National Cancer Database) demonstrated better overall survival with BT-boost (low dose rate LDR or high dose rate HDR) compared with DE-EBRT. These recent findings demonstrate the superiority of EBRT+BT-boost+ADT versus DE-EBRT+ADT for HR-PCa. It seems that EBRT+BT-boost+ADT could now be considered as a gold standard treatment for HR-PCa. HDR or LDR are options. SBRT-boost represents an attractive alternative, but the absence of randomised trials does not allow us to conclude for HR-PCa. Prospective randomised international phase III trials or meta-analyses could improve the level of evidence of SBRT-boost for HR-PCa.

Patient-reported functional outcomes following external beam radiation therapy for prostate cancer with and without a high-dose rate brachytherapy boost: A national population-based study.

BACKGROUND AND PURPOSE: Little is known about the functional outcomes and health-related quality of life (HRQoL) following external beam radiation therapy (EBRT) combined with a high-dose rate brachytherapy boost (EBRT-BB) for the treatment of prostate cancer. We aimed to compare patient-reported outcomes of EBRT to those of EBRT-BB. METHODS AND MATERIALS: Patients diagnosed with intermediate-risk, high-risk or locally advanced prostate cancer (April 2014 to September 2016), who received EBRT in the English National Health Service within 18 months of diagnosis and responded to a national patient questionnaire, were identified from the National Prostate Cancer Audit. Adjusted linear regression was used to estimate differences in functional EPIC-26 domains and HRQoL (EQ-5D-5L) between treatment groups. Non-inferiority of EBRT-BB was determined if the lower 95% confidence limit did not exceed the established minimal clinically important difference (MCID). RESULTS: Of the 13,259 included men, 12,503 (94.3%) received EBRT and 756 (5.7%) received EBRT-BB. EBRT-BB was non-inferior compared to EBRT for the urinary incontinence, sexual, bowel and hormonal EPIC-26 domains. EBRT-BB resulted in significantly worse urinary irritation/obstruction scores than EBRT (-6.1; 95% CI: -8.8 to -3.4) but uncertainty remains as to whether this difference is clinically important (corresponding MCID of 5). CONCLUSIONS: There is no evidence to suggest that EBRT-BB results in any clinically important detriment in functional outcomes or HRQoL compared to men receiving EBRT only. Whilst statistically significantly worse urinary irritation/obstruction outcomes were reported in the EBRT-BB cohort, the threshold for a clinically significant difference was not exceeded and further research is required for confirmation.

Image-guided interstitial brachytherapy boost for nasopharyngeal carcinoma: technical aspects.

Nasopharyngeal cancer generally responds well to concurrent chemoradiotherapy (CCRT). However, there is a small group of patients who respond poorly to CCRT, and experience local residual tumor or local relapse. Although several attempts have been performed to such a group of patients including re-irradiation with external beam radiation therapy (EBRT) or salvage surgery, clinical results remain unsatisfactory. Intracavitary brachytherapy (ICBT) boost after CCRT with EBRT has been explored, however, its efficacy is limited to those with superficial residual tumors. For those residual tumors thickness with more than 5 mm, interstitial brachytherapy (ISBT) boost would be an appropriate modality of choice. Here, we describe technical aspects of the high-dose-rate interstitial brachytherapy (HDR-ISBT) boost for nasopharyngeal cancer (NPC) patients who responded poorly to the CCRT with EBRT.

Transperineal mapping biopsy improves selection of brachytherapy boost for men with localized prostate cancer.

PURPOSE: To determine if transperineal mapping biopsy (TPMB) can improve the selection of brachytherapy alone (BT) or brachytherapy boost (BTB) in men with localized prostate cancer. METHODS AND MATERIALS: Two hundred and eighteen men underwent TPMB with a mean of 48.6 cores retrieved. Comparisons were made between prebiopsy risk features and biopsy results to treatment choice with associations tested with ANOVA (bootstrap), χ2 test (Pearson), and linear regression. Survival estimates were tested by the Kaplan-Meier method with comparisons by log rank. RESULTS: Mean age, prostate specific antigen (PSA), prostate specific antigen density (PSAD), and prostate volume were 67.2 years, 8.1 ng/mL, 0.19, and 50.3 cc, respectively. 105 (48.2%) biopsies were positive for Gleason Group (GG) 1: 34 (32.4%), 2: 21 (20%), 3: 31 (29.5%), 4: 7 (6.7%), and 5: 12 (11.4%). The mean number of positive cores (PCs) was 7.3 (median 6, range 1-37). Men with six or more PCs had higher PSA (11.3 vs. 6.0 ng/mL, p = 0.025) and PSAD (0.34 vs. 0.13, p = 0.013). Overall brachytherapy was used in 74 (70.5%) as either monotherapy or boost therapy. Men with BTB had higher PSA (9.7 vs. 6.7 ng/mL, p = 0.029), PSAD (0.27 vs. 0.16, p = 0.007), GG (3.3 vs. 1.8, p < 0.001), more bilateral disease (75.9% vs. 55.6%, odds ratio 3.9, p = 0.008), and PCs (10.9 vs. 4.4, p < 0.001). On linear regression, only GG (p = 0.008) and PCs (p = 0.044) were associated with BTB. Biochemical-free failure at 5 years was 92.7%. CONCLUSIONS: TPMB improves the selection of patients for BTB. Men with more PCs are more likely to have BTB. Restricting the need for BTB to those with greater volume prostate cancer may reduce radiation side effects.