High Dose Rate Brachytherapy Boost Research Articles

Differential outcomes of re-stratified high-risk prostate cancer patients treated with external beam radiation therapy plus high-dose-rate brachytherapy boost.

We report outcomes of high-risk prostate cancer (PCa) patients, initially classified according to a 3-tier NCCN classification system, treated with external beam radiation therapy (EBRT) and high-dose-rate brachytherapy boost (HDR-BT). Patients were analyzed based on a re-stratification of their risk grouping using CAPRA score and a newer 5-tier NCCN classification. 471 high-risk PCa patients treated with EBRT, HDR-BT, and androgen deprivation therapy (ADT) between 1999 and 2018 were included. Competing risk survival analyses to compare individuals with CAPRA scores < 6 vs. ≥ 6 for biochemical relapse (BCR) and metastasis incidence were conducted. Also, overall survival (OS) for both groups using Kaplan-Meier analysis was assessed. The same analyses were repeated using a 5-tier NCCN stratification comparing those classified as high-risk vs. very high-risk patients. The median age was 71 years, and the median follow-up period was 72 months. The whole cohort received an EQD2 of 74 Gy or greater, with a median EQD2 of 106.89 Gy. Both a CAPRA score ≥ 6 and belonging to the NCCN very high-risk group were associated with BCR, with subdistribution hazard ratios (sHRs) of 3.04 (p = 0.015) and 2.53 (p = 0.013), respectively. For metastasis incidence, both the CAPRA and NCCN groups had similar sHRs of 2.60 (p = 0.094) and 2.71 (p = 0.037), respectively. For 10-year OS, patients with CAPRA score ≥ 6 and belonging to the NCCN very high-risk group presented similar HRs of 2.11 (p = 0.005) and 2.10 (p = 0.002). We showed that high-risk PCa patients classified according to the 3-tier NCCN system benefit from further stratification using the CAPRA score or the 5-tier NCCN stratification method. Patients with a CAPRA score ≥ 6 or classified as very high-risk demonstrate a higher hazard of BCR, metastasis, and death. These patients might benefit from further intensification of their investigations and treatment, based on ongoing research.

Comparison of Low Dose Rate and High Dose Rate Brachytherapy Boost Techniques in Prostate Cancer: Evaluation of Toxicity.

The ASCENDE-RT trial has been criticized for higher rates of chronic severe toxicity (18% genitourinary (GU)) than expected with a low dose rate (LDR) boost technique. We compared clinical outcomes of LDR and high dose rate (HDR) boost in the acute and chronic setting from a large single institution experience over a continuous 20-year period, with a focus on GU and gastrointestinal (GI) toxicity during treatment of prostate cancer. We retrospectively reviewed patients treated with LDR boost (2003 - 2013) and HDR boost (2014 - 2018). Clinical and treatment-related prognostic factors including age, stage, androgen deprivation therapy (ADT), dosimetry details, and toxicity data were recorded. Toxicity was scored according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Multi-variable analysis (MVA) was performed to evaluate variables associated with toxicity. A total of 184 men were evaluated (87 LDR and 97 HDR) with a median follow-up of 7.1 years and 4.0 years, respectively. Most patients (92% LDR and 57% HDR) received ADT in addition to BT. The median EBRT dose was 46 Gy for LDR and 45 Gy for HDR (range 25 - 50 Gy). Prostate D90% was similar at 104% and 105% in the LDR and HDR groups, respectively. Urethra D10% and Rectum V100% were both higher with LDR compared to HDR with 155% vs 119% and 0.436% vs 0.073%, respectively. Severe (grade 3+) toxicity was rare (Table 1), with 3.4% of LDR patients experiencing grade 3 chronic GU toxicity. With HDR, 3.1% and 1% of patients experienced acute and chronic grade 3 GU toxicity, respectively. Although non-severe GU toxicity (grade 1-2) was similar between groups (95% LDR vs 89% HDR, p = 0.16), LDR patients experienced more grade 2 GU events (80.5% acute; 82.8% chronic) compared to HDR patients (45.4% acute; 57.7% chronic). There were no severe GI toxicities in the acute or chronic period. Non-severe acute GI toxicity was more common with HDR, while non-severe chronic GI toxicity was more common with LDR. On MVA, acute GU toxicity (any grade) was associated with short term ADT (p = 0.01) and Urethra D10% (p < 0.05); Chronic GU toxicity (any grade) was associated with age (p = 0.09) and Prostate V150cc (p = 0.07) but not BT boost technique. This comparative retrospective analysis of BT boost techniques reveals the overall rate of severe GU and GI toxicity to be low with both LDR and HDR. HDR boost appears to have a slightly more favorable ratio of Grade 1 to Grade 2 GU toxicity and improved urethra/rectum dosimetry. Our analysis suggests that the dosimetric advantages of HDR may deliver small reductions in GU toxicity.

Patient-Reported Urinary and Bowel Quality of Life Outcomes Following External Beam Radiotherapy with or without High-Dose-Rate Brachytherapy Boost: Post-Hoc Analyses of TROG 03.04 (RADAR)

One of the concerns with combining external beam radiotherapy (EBRT) with a high dose rate brachytherapy boost (HDRBT) for prostate cancer is increased toxicity. We aimed to evaluate long-term urinary and bowel quality of life (QoL) outcomes following EBRT vs EBRT + HDRBT using data from the TROG 03.04 trial. Men who had dose-escalated EBRT (74 Gy) or EBRT (46 Gy) + HDRBT (19.5 Gy in 3 fractions) were included in this exploratory analysis. QoL outcomes were prospectively collected using the EORTC-QLQ-PR25 at baseline, end of radiotherapy, 12, 18, 24, 36, 60 months, and annually up to 10 years. QoL score was normalized to 0-100 with higher scores representing worse symptom burden. Minimal clinically important differences (MCIDs) were defined as differences in the respective QoL scores ≥0.5 standard deviations of the baseline QoL score. Mixed models for repeated measures were used to evaluate longitudinal changes in the QoL score between EBRT and EBRT + HDRBT arms. Logistic regression was used to evaluate differences in proportion of men with 2xMCID between EBRT and EBRT + HDRBT arms at each time point. Age, baseline QoL score, ECOG performance status, and duration of androgen deprivation therapy use (6 vs. 18 months) were adjusted for in all analyses. Four hundred ninety-seven men were included in this study: 260 (52%) had EBRT and 237 (48%) had EBRT + HDRBT. The median baseline urinary QoL scores were 12.5 (IQR 4.2-19.0) and 8.3 (IQR 4.2-20.8) for men in EBRT and EBRT + HDRBT arms respectively (P = 0.5). Within the first 24 months, men in the EBRT + HDRBT arm had a slower rate of urinary QoL score resolution compared to men in the EBRT arm (P<0.001). At 12, 18, 24, and 36 months, men who had EBRT + HDRBT were 2.4 times (95% CI = 1.4-4.0; P<0.001), 3.1 times (95% CI = 1.8-5.1; P<0.001), 2.8 times (95% CI = 1.7-4.7; P<0.001), and 2.5 times (95% CI = 1.4-4.5; P = 0.002) more likely to have 2xMCID in urinary QoL scores compared to men who had EBRT alone. Beyond 24 months, there were no significant differences in the rate of urinary QoL score resolution between arms, and beyond 36 months there were no significant differences in the proportion with 2xMCID between arms. The median baseline bowel QoL score was 0 in both arms. There were no differences in the rate of bowel QoL score recovery over time between arms. Men who had EBRT + HDRBT were less likely to have 2xMCID in bowel QoL score in the immediate post-radiotherapy period (OR = 0.66; 95% CI = 0.45-0.97; P = 0.03) and at 60 months (OR = 0.51; 95% CI = 0.33-0.80; P = 0.003) compared to men who had EBRT. EBRT + HDRBT is associated with disturbances in urinary QoL that are of greater magnitude compared to EBRT alone within the first 36 months of treatment, but the differences resolved after 36 months. EBRT + HDRBT is associated with less disturbances in bowel QoL immediately after treatment and at 60 months compared to EBRT alone.

Phase III Study of Hypofractionated, Dose Escalation Radiotherapy vs. Conventional Pelvic Radiation Therapy followed by High Dose Rate Brachytherapy Boost for High Risk Adenocarcinoma of the Prostate (PCS VI): Acute Toxicity Results

The low α\β ratio of 1.2-2 for prostate cancer (PCa) suggests high radiation-fraction sensitivity and predicts a therapeutic advantage of lager fraction size. We have recently shown (PCS5) that high risk prostate cancer patients can safely and effectively be treated with moderate hypofractionated radiation therapy (HF-RT). To date there has been no phase-III randomized clinical-trial comparing moderately HF-RT with EBRT and HDR boost (HDRB). We are reporting the acute safety of EBRT+HDRB compared to moderate HF-RT in this phase III Canadian trial. From January 2015-June 2022, 308 high-risk localized PCa patients were randomized to receive either HF-RT or EBRT+HDRB. All patients received neo-adjuvant, concurrent, and long-term adjuvant androgen deprivation therapy (ADT). EBRT+HDRB consisted of 46 Gy in 2 Gy per fraction to the pelvis and a 15 Gy in one fraction HDR boost within 3 weeks of EBRT. HF-RT include concomitant dose escalation of 68 Gy in 2.72 Gy per fraction to the prostate, and 45 Gy in 1.8 Gy per fraction to the pelvic lymph-nodes. Of the 308 patients, 148 received HF-RT and 144 EBRT+ HDRB. The remainder either withdrew from the study or were treated with standard (2 Gy per fraction) fractionation for technical reasons. In both intention to treat and as treated analysis, using log-Rank, there were more grade 1 or worse (G1+) acute GI and GU events and more G2+ acute GI events in the HF-RT than EBRT+HDRB. As treated analysis the acute G1+ and G2+ GI events were 92 vs 77 (60.1% vs. 53.5%; p < 0.017) and 21 vs 10 (13.7% vs. 6.9%; p = 0.052), respectively for HF-RT and EBRT + HDRB. Similarly, the G1+ acute GU events were 123 vs. 101 (80.4% vs.70.1%; p < 0.001) respectively for HF-RT and EBRT+HDRB. There were only four G3 GI and one G3 GU acute toxicities in both arms. No grade 4 toxicities were reported. This is the first study of EBRT+HDRB compared to moderate HF dose escalated RT in high-risk prostate cancer patients treated with long-term ADT and pelvic RT. Our results demonstrate that both treatment approaches are well-tolerated and that EBRT+HDRB carries less G2+ GI and G1+ GU acute toxicities.

Stereotactic Body Radiation Therapy and High-Dose Rate Brachytherapy Boost in Combination with Intensity Modulated Radiation Therapy for Localized Prostate Cancer: A Single-Institution Cohort Study

The use of dose-escalated external beam radiation (EBRT) and brachytherapy (BT) boost with ADT has emerged as an option with superior biochemical control compared to dose-escalated EBRT alone. BT is traditionally delivered using low-dose rate techniques, but more recently high-dose rate (HDR) BT has also emerged as a boost option for these patients with promise of low toxicity rates. SBRT is a favorable modality for monotherapy for low and intermediate risk group patients, however its safety and efficacy as a boost in combination with EBRT is less well understood. The aim of this study is to compare SBRT boost, HDR boost and LDR boost for localized prostate cancer. A single-institution retrospective chart review was performed of men receiving EBRT delivered using intensity modulated RT and either SBRT boost (650cGy x 3), HDR-BT boost (1500cGy x 1), or LDR boost with I-125 (110Gy). Of patients treated w/ SBRT boost, 39 (80%) were treated with an SIB to the MRI-detectable lesion(s) to 700cGy x 3. Treatment characteristics for each strategy were reviewed and on-treatment toxicity outcomes for each of the cohorts were compared using Chi-square tests. From 2017-2022, 49 patients were treated with EBRT+SBRT boost, 44 patients received EBRT+ HDR-BT boost, and 46 patients received EBRT+ LDR-BT boost. The average age of patients included in the study was 71.2 years (median age 69.55 years, range 51.42-83.70 years) with average baseline PSA of 11 (median 7.6, range 3.3-64). In addition, 55% of the patients had high-risk/very high-risk disease, 39% had unfavorable intermediate disease and 6% had favorable intermediate disease. 139 patients received androgen deprivation therapy (93%). There were no differences in these baseline demographics and clinical or treatment factors between SBRT, HDR and LDR boost (p>0.05). The median dose/fx of EBRT was 4500cGy/25 fx (range 4500-5040cGy/23-28 fractions). At the end of treatment, 69% of the patients had 0-1 change in nocturia. There is an increase in nocturia episodes of 2-3 from baseline in 27% of the patients, while 4% had an increase in nocturia episodes of 4 or more from baseline with no difference between the SBRT, HDR and LDR boost. At baseline 36 patients (26%) reported urinary frequency symptoms, increasing to 80 patients (58%) by end of treatment with no difference between the SBRT, HDR and LDR boost. Similarly, there was a trend to increased use of urinary modifiers at end of treatment in patients treated with EBRT+HDR boost compared to EBRT+SBRT and EBRT+ LDR boost (89% vs. 71% v 72% respectively). There was no significant difference in acute urinary toxicity and nocturia between SBRT, HDR and LDR boost (p>0.05).

PO55: High Dose Rate Brachytherapy Boost versus Monotherapy in Unfavourable-Intermediate and High Risk Localized Prostate Cancer: Retrospective Australian Single-Institutional Experience with Long-Term Follow-Up

PO55: High Dose Rate Brachytherapy Boost versus Monotherapy in Unfavourable-Intermediate and High Risk Localized Prostate Cancer: Retrospective Australian Single-Institutional Experience with Long-Term Follow-Up

Outcomes following brachytherapy boost for intermediate- and high-risk prostate cancer: A retrospective bicenter study by the SFRO brachytherapy group

IntroductionRadiotherapy dose escalation improves biochemical control in intermediate- or high-risk prostate cancer. Brachytherapy boost was shown to further improve biochemical control compared to radiotherapy alone in three randomized trials. The SFRO brachytherapy group sought to evaluate the efficacy and toxicity of BT-boost for intermediate and high-risk prostate cancer in real life, and to determine prognostic factors for efficacy and toxicity. Material and methodA retrospective study was conducted, including all patients with intermediate- or high-risk prostate cancer treated with a combination of external beam radiotherapy (EBRT) and high dose-rate brachytherapy boost (HDR-BB), from 2006 until December 2019 at two centers. Patient characteristics, initial disease, treatment and follow-up were collected. Results709 patients from two centers were analyzed given a short follow-up in the other centers. Out of those, 277 were intermediate risk (170 favorable and 107 unfavorable) and 432 were high risk. The median EBRT and HDR-BB doses were 46 Gy (35–50) and 14 Gy (10–20). After a median follow-up of 62 months, biochemical control at 5 years was 87.5 % for the overall population, 91 % and 85 % for intermediate- and high-risk cancers, respectively. At 5 years, biochemical and clinical relapse-free survival, metastasis-free survival and local control rates were 83 %, 90 % and 97 % respectively. 5-years overall survival was 94 %. Late grade 2 or higher GU or GI toxicity was found in 36 patients (5 %) and 9 patients (1.3 %). ConclusionThis bicenter analysis shows the efficacy and tolerability of HDR-BB as a complement to external radiotherapy. Further improvements such as combination with new hormonal agents or new brachytherapy-radiotherapy fractionation regimens are warranted to improve further the outcomes and therapeutic ratio.

Hypofractionated Whole-Breast-IMRT with HDR Brachytherapy Boost in Early-Stage Breast Cancer: Long Term Results of a Single Center Study

<h3>Purpose/Objective(s)</h3> In breast cancer patients, the addition of a boost over the lumpectomy bed after whole breast radiotherapy is frequently included in the therapeutic protocol and interstitial brachytherapy (BT) is one of the options for its administration. When BT is performed after conventional fractionation (50Gy) is considered safe, effective and strongly supported by literature. However, few studies have described its efficacy and side effects after a hypofractionated scheme, and even fewer have reported treatment/patient-dependent factors that may influence toxicity. The aim of this study is to show our results from a group of patients treated under a hypofractionated forward-planned whole-breast IMRT (Hypo-WB-IMRT) scheme followed by a high-dose-rate brachytherapy boost (HDR-BT) after conservative surgery. <h3>Materials/Methods</h3> We evaluated all patients treated at our facility with Hypo-WB-IMRT without elective irradiation of lymphatic areas (40Gy/15sessions) with a sequential single application of HDR-BT of 7 to 12Gy. A breast MRI was performed in all patients at the time of diagnosis. The BT implant was designed using both diagnostic MRI and planning CT as a reference for tumor bed localization and was planned according to the modified Paris system, with rigid needles, local anesthesia and outpatient regimen. <h3>Results</h3> Between 2009 and 2017, 638 patients with early-stage invasive breast cancer or ductal carcinoma in situ received adjuvant treatment according to the aforementioned protocol after breast-conserving surgery. Median follow-up was 6 years (4-11ys). We did not identify any relationship between the volume in cubic centimeters of the isodoses of 90%, 100%, 120% and 150% of the prescribed dose with acute (bleeding, mastitis) or long-term toxicity (12-month fibrosis, pain, edema, hypochromia, telangiectasia) or with an increased likelihood of local relapse or a second primary tumor in the same breast. However, and despite the low incidence of side effects and their slightness, we did identify an impact of breast volume with an increased risk of radiodermatitis at the end of WBRT (p=0.019), post-treatment mastitis (p=0,023), tumor bed fibrosis after 12 months (p=0.002), chronic pain (p=0.018) and breast edema (p<0.001) in women with >1000cc breasts with respect to smaller volume breasts. 13 patients had an actual local relapse (2.21%), 14 had a 2^nd primary in the same breast (2.39%) and 14 were diagnosed with contralateral breast cancer (2.39%). 16 patients (2.73%) developed metastatic disease and the overall survival at 11 years was 85.5%. <h3>Conclusion</h3> Hypo-WB-IMRT followed by a single dose HDR-BT boost is well tolerated, with a low rate of side effects and excellent oncologic outcomes. However, it may be of interest to individualize the treatment protocol choice in large breasts women who may be at higher risk of toxicity.

High Dose Rate Brachytherapy Boost After Chemoradiation in Rectal Cancer Patients: A Retrospective Study

Background: The use of neoadjuvant chemoradiation has enhanced local control in rectal cancer patients. Objectives: The aim of this study was to evaluate the feasibility and efficacy of adding a high dose rate (HDR) brachytherapy (BRT) boost in locally advanced rectal cancer. Methods: This retrospective trial was conducted based on the medical records of patients with rectal cancer, who were referred to a tertiary hospital for neoadjuvant treatment. Fifteen patients who were treated with HDR brachytherapy boost after completion of external beam radiotherapy (EBRT) and concurrent chemotherapy were enrolled in the intervention group and 15 patients who were clinically matched (age, sex, stage, and distance of tumor from anal verge) were selected as the control group. EBRT schedule and concurrent chemotherapy regimen were similar in the two groups. The rate of pathological complete response (PCR), downstaging (T staging), and frequency of side effects were compared between the two groups of the study. Results: The mean age of patients was 57.97 ± 9.11 years and 18 patients (60%) were male. The results showed that T 3 and N 1 rectal cancer had the highest frequency among patients. Downstaging was observed in 66.7% and 80% of the control and intervention groups, respectively (P: 0.40). The rate of PCR was not different in the two groups (13.3% in both groups, P &gt; 0.99). There were no significant differences in terms of treatment complications between the two groups, as well. Conclusions: HDR-BRT boost for rectal cancer is feasible and might improve downstaging in rectal cancer, but not PCR.

Toxicity Related Patients Factors and Bevasizumab Use in Patients With Locally Advanced Cervical Cancer Treated With Definitive Chemoradiation and HDR Brachytherapy Boost

The purpose of this study is to identify factors associated with severe late toxicity and prognosis in women with locally advanced cervical cancer treated with definitive chemoradiation (CRT) and high dose rate (HDR) radiation therapy boost. An increased rate of GI toxicity when Bevacizumab is administered in combination with high doses of abdominal radiation therapy such as stereotactic body radiotherapy (SBRT) has been demonstrated in other malignancies. Our aim is to compare the risk of Grade 3+ toxicity in patients who receive Bevacizumab after HDR brachytherapy in comparison with other risk factors.Patients with locally advanced cervical cancer treated with CRT from 2010-2019 in a single academic institution were included. Records were reviewed for demographic information, treatment details, toxicities, and outcomes. Patients with and those without severe late gastrointestinal (GI) toxicity and severe late genitourinary (GU) toxicity were compared. Progression free-survival (PFS) was also compared between groups. Smoking status was classified as current smokers, former smokers and non-smokers. Statistical comparisons were performed using t-tests and ANOVA tests.Of 101 patients identified, 10.9% had severe grade 3+ GI toxicity, and 9.1% had severe grade 3+ GU toxicity. Mean duration to follow up was 30 months (range 1-124 months). In patients who received Bevacizumab after completion of definitive treatment, there was a significantly higher rate of Grade 3+ GI or GU toxicity (50% versus 16%, P = 0.005). 83% of Grade 3+ toxicity in the Bevacizumab group was GI related. There was no correlation between the time interval between radiation and Bevacizumab initiation to toxicity. Age was also significantly associated with toxicity, patients 55 and younger had a 10% rate of Grade 3+ toxicity while patients older than 55 had a 28% rate (P = 0.02). Patient who received interstitial versus intracavitary brachytherapy technique also demonstrated high rates of toxicity (30% vs. 8%, P = 0.002). PFS was similar among patients with severe toxicities compared to those without toxicity. In regards to smoking status, there was no significant difference in toxicity. Risk of recurrence was higher in the current smokers and former smokers (40% and 31% respectively) but did not reach statistical significance when compared to non-smokers (25%).In patients with locally advanced cervical cancer, the use of Bevacizumab is significantly associated with increased toxicity after definitive chemoradiation. Similar data has been shown in patients who receive Bevacizumab and abdominal SBRT. Given that the addition of Bevacizumab is first-line therapy and improves survival for recurrent cervical cancer, further investigation is warranted to determine how to optimize the risk-benefit ratio.S. Azghadi: None. P.L. Beagen: None. A. Ahmed: None. R.K. Valicenti: None. R.A. Brooks: None. X. Zhao: None.

Stereotactic pelvic radiotherapy with HDR boost for dose escalation in intermediate and high-risk prostate cancer (SPARE): Efficacy, toxicity and quality of life

BackgroundThe ASCO/CCO guidelines recommend brachytherapy (BT) boost for eligible intermediate- (IR) or high-risk (HR) prostate cancer (PCa) patients. We present efficacy, toxicity and quality-of-life (QoL) outcomes in patients treated on a prospective protocol of MRI dose-painted high-dose-rate BT boost (HDR-BT) followed by 5-fraction pelvic radiotherapy (RT) and 6–18 months of androgen deprivation therapy (ADT). MethodsIn this phase I/II study, IR or HR PCa patients received HDR-BT 15 Gy × 1 to prostate and up to 22.5 Gy to MRI nodule, followed by 25 Gy in 5, weekly fractions to pelvis. Toxicity was assessed using CTCAEv3.0, and QoL was captured using EPIC questionnaire. Biochemical failure (BF; nadir + 2.0), and proportion of patients with PSA < 0.4 ng/ml at 4-years (4yPSARR) were evaluated. A minimally clinically important change (MCIC) was recorded if QoL score decreased >0.5 standard deviation of baseline scores. ResultsThirty-one patients (NCCN 3.2% favorable IR, 48.4% unfavorable IR and 48.4% HR) completed treatment with a median follow-up of 61 months. Median D90 to MR nodule was 19.0 Gy and median prostate V100% was 96.5%. The actuarial 5-year BF rate was 18.2%, and the 4yPSARR was 71%. One patient died of PCa. Acute grade 2 and 3 toxicities: GU: 50%, 7%, and GI: 3%, none, respectively. Late grade 2 and 3 toxicities were: GU: 23%, 3%, and GI: 7%, none, respectively. Proportion of patients with MCIC was 7.7% for urinary domain and 32.0% for bowel domain. ConclusionsThis novel treatment protocol incorporating MRI dose-painted HDR-BT boost and 5-fraction pelvic RT with ADT is well tolerated.

GSOR12 Presentation Time: 3:25 PM: Toxicity Related Patients Factors and Bevacizumab Use in Patients with Locally Advanced Cervical Cancer Treated with Definitive Chemoradiation and HDR Brachytherapy Boost

Purpose: The purpose of this study is to identify factors associated with severe late toxicity and prognosis in women with locally advanced cervical cancer treated with definitive chemoradiation (CRT) and high dose rate (HDR) radiation therapy boost. An increased rate of GI toxicity when Bevacizumab is administered in combination with high doses of abdominal radiation therapy such as stereotactic body radiotherapy (SBRT) has been demonstrated in other malignancies. Our aim is to compare the risk of Grade 3+ toxicity in patients who receive Bevacizumab after HDR brachytherapy in comparison with other risk factors.

Dosimetric Comparison between High Dose Rate Brachytherapy Boost and Volumetric Arc Therapy Boost in Locally Advanced Cancer Cervix

Concurrent chemoradiotherapy is considered the standard treatment for the locally advanced cancer cervix (LACC). Radiotherapy is commonly administered by a three-dimensional conformal radiotherapy (3DCRT) approach followed by brachytherapy (BT). High dose rate (HDR) BT is commonly administered; however, several drawbacks exist including invasive technique, pain, requirement of anesthesia, and operative risks. We assessed the dosimetric difference between the HDR BT and the volumetric modulated arc therapy (VMAT) boost in those patients. Ten patients were selected retrospectively with LACC and all received whole pelvis radiotherapy followed by BT boost of 7 Gy in three fractions. The computed tomography (CT) image was transferred to the Varian system for the VMAT plan while the one with the applicator was transferred to the Sagi planning system and the high-risk clinical target volume (HR-CTV), bladder, rectum, sigmoid, and small bowel were delineate with a margin of 5 mm were added to the CTV to create the planning target volume (PTV). The D90 for the PTV in VMAT boost was lower than received by the HR-CTV in the BT boost. Mean volume of the PTV was higher than that of the HR-CTV. The D2cc was higher in VMAT for bladder, sigmoid, and rectum while the D2cc for the small bowel in BT was higher compared with the VMAT. The VMAT is an option that exists for patients who refuse BT or cannot tolerate it, or in case of nonavailability of BT or a nonworking machine.

Impact of High-Dose-Rate and Low-Dose-Rate Brachytherapy Boost on Toxicity, Functional and Cancer Outcomes in Patients Receiving External Beam Radiation Therapy for Prostate Cancer: A National Population-Based Study

External beam radiation therapy (EBRT) with brachytherapy boost reduces cancer recurrence in patients with prostate cancer compared with EBRT monotherapy. However, randomized controlled trials or large-scale observational studies have not compared brachytherapy boost types directly. This observational cohort study used linked national cancer registry data, radiation therapy data, administrative hospital data, and mortality records of 54,642 patients with intermediate-risk, high-risk, and locally advanced prostate cancer in England. The records of 11,676 patients were also linked to results from a national patient survey collected at least 18 months after diagnosis. Competing risk regression analyses were used to compare gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, skeletal-related events (SRE), and prostate cancer-specific mortality (PCSM) at 5 years with adjustment for patient and tumor characteristics. Linear regression was used to compare Expanded Prostate Cancer Index Composite 26-item version domain scores (scale, 0-100, with higher scores indicating better function). Five-year GI toxicity was significantly increased after low-dose-rate brachytherapy boost (LDR-BB) (32.3%) compared with high-dose-rate brachytherapy boost (HDR-BB) (16.7%) or EBRT monotherapy (18.7%). Five-year GU toxicity was significantly increased after both LDR-BB (15.8%) and HDR-BB (16.6%), compared with EBRT monotherapy (10.4%). These toxicity patterns were matched by the mean patient-reported bowel function scores (LDR-BB, 77.3; HDR-BB, 85.8; EBRT monotherapy, 84.4) and the mean patient-reported urinary obstruction/irritation function scores (LDR-BB, 72.2; HDR-BB, 78.9; EBRT monotherapy, 83.8). Five-year incidences of SREs and PCSM were significantly lower after HDR-BB (2.4% and 2.7%, respectively) compared with EBRT monotherapy (2.8% and 3.5%, respectively). Compared with EBRT monotherapy, LDR-BB has worse GI and GU toxicity and HDR-BB has worse GU toxicity. HDR-BB has a lower incidence of SREs and PCSM than EBRT monotherapy.

Contemporary External Beam Radiotherapy Boost or High Dose-Rate Brachytherapy Boost for Cervical Cancer: A Propensity-Score–Matched, Nationwide, Population-Based Cohort Study

Purpose: To estimate the survival effects of contemporary external beam radiotherapy (EBRT) boost modalities (intensity-modulated radiation therapy or volumetric modulated arc therapy) and high dose-rate brachytherapy (HDR-BT) boost in patients with cervical cancer (CC). Patients and Methods: Patients who had been diagnosed as having CC were recruited from the Taiwan Cancer Registry Database. Propensity score matching was performed, and Cox proportional-hazards model curves were used to analyze the all-cause mortality of patients who received standard whole-pelvis irradiation with different boost modalities. Results: The matching process yielded a final cohort of 1,630 patients (815 in the EBRT boost and HDR-BT boost groups, respectively) eligible for further analysis. The multivariate Cox regression analyses indicated that the adjusted hazard ratio (95% confidence intervals) for EBRT boost compared with HDR-BT boost was 1.62 (1.43–1.84). Multivariable analysis revealed that the independent poor prognostic factors of all-cause mortality among patients with CC were adenocarcinoma, no chemotherapy, EBRT boost, Charlson comorbidity index score ≥ 1, age ≥ 60 years, and advanced International Federation of Gynecology and Obstetrics stage. Conclusions: HDR-BT boost may be more beneficial than contemporary EBRT boost in selected patients with CC. Funding Statement: Lo-Hsu Medical Foundation, LotungPoh-Ai Hospital, supports Szu- Yuan Wu’s work (Funding Number: 10908 and 10909). Declaration of Interests: The authors have no potential conflicts of interest to declare. Ethics Approval Statement: Our protocols were reviewed and approved by the Institutional Review Board of Taipei Medical University (TMU-JIRB No. 201702019).

Utilization of an Applicator System Including a Tandem with Multi-Directional Interstitial Needle-Guide Ring and Perineal Template for High Dose Rate Brachytherapy Boost Treatments of Large-Volume Cervical Adenocarcinoma

To study the ability of a gynecological applicator system of a tandem with a pair of lunar ovoids with multi-directional needle guides and a perineal template to appropriately provide large-volume boost High Dose Rate Brachytherapy (HDR) treatment to cervical adenocarcinoma. Three HDR boost plans of patients with large target volumes (121 – 224 cm3) were used for dosimetric performance evaluation. All patients used an applicator with a tandem and a pair of needle-guide lunar ovoids, and two patients used the perineal template additionally for some fractions. The investigated applicator is different from other integrated needle-guide applicators because the ovoids have needle guides that curve the interstitial needles out 30-degrees relative to the direction of the tandem, thus allowing dwell locations farther from midline. The number of needles loaded depended on the extension of the target volume and ranged from 10 to 21 needles. Based on patient anatomy, the needles were placed and pushed as far as it was necessary under ultrasound guidance. On average, the straight channels were inserted 6.5 cm and flared channels 4.6 cm from the ring. Plans were optimized to the high-risk target volume (HRCTV) using inverse optimization to an expanded planning volume HRCTV-OPTI, which included the HRCTV and the area around the lunar ovoids with standard constraints based on GEC-ESTRO recommendations. For each patient, coverage of the HRCTV was achieved with 90% of the volume receiving at least 100% of the prescription dose (Mean 106.3%). Target conformity was 0.69 on average. The total reference dose volume for the three patients in this study ranged from 156 to 289 cm3. The typical total reference dose volume when treating with a standard loading to point A with no needles was 83 to 93 cm3 depending on the applicator size. Average dose as percentage of the prescription dose to the 2 cm3 volume of the Bladder, Rectum, Sigmoid, and Bowel were 78.9%, 68.2%, 70.6%, and 50.9% respectively. Dose to Point A on average was over 204%. Patient tolerance of repeated interstitial needle placement was reported to be good, with low to moderate bleeding and pain post-procedure. All patients showed response to treatment, with one showing total pelvic control on follow-up. Planning time per fraction increased to a mean of 1.7 hours, from an average of 1 hour for a standard tandem and ring treatment, with total average procedure time of 4 hours (2 hr. 19 min. - 5 hr. 54 min.). Multi-directional needle-guide applicators for cervical HDR are useful in creating high quality plans that meet target and organ constraints for volumes that are much larger than the standard, without substantial sacrifice of patient comfort or time in spite of the added treatment planning complexity.

Randomised trial of external-beam radiotherapy alone or with high-dose-rate brachytherapy for prostate cancer: Mature 12-year results

Background and purposeA randomised phase-III trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate adenocarcinoma. Previous analysis, at median follow up of 85 months, demonstrated improved relapse free survival (RFS) with EBRT + HDR-BTb. This data has now been updated with a median follow up of 131 months. Materials and methodsFrom December 1997 to August 2005, patients were assigned either to EBRT alone delivering 55 Gy in 20 fractions over 4 weeks or EBRT followed by a temporary high-dose-rate implant delivering 2 × 8·5 Gy over 24 h. The primary endpoint was RFS defined by a PSA rise ≥2.0 µg/l above nadir, clinical progression or death. Actuarial survival rates and Hazard Ratios (HRs) were calculated using the Kaplan–Meier method and Cox’s Proportional Hazard Model, respectively. Secondary endpoints were overall survival (OS), urinary and bowel toxicity. ResultsOne hundred and six patients received EBRT alone and 110 EBRT + HDR-BTb. Median time to relapse was 137 months in the HDR-BTb arm compared to 82 months for EBRT alone (p = 0·01). A 27% risk of recurrence with EBRT alone was observed (p = 0·001), resulting in a 21% improvement in RFS at 12 years with EBRT + HDR-BTb. In multivariate analysis treatment arm, risk category and no androgen deprivation therapy were significant covariates for risk of relapse. Differences in overall survival were not significant. ConclusionAt 12 years there remains a significant improvement in RFS after EBRT + HDR-BTb; both treatments were equitoxic for severe late urinary and bowel events and urethral strictures.

Estimating acute urinary retention risk post prostate high dose-rate (HDR) brachytherapy: A clinical-based recursive partitioning analysis

PurposeTo determine factors associated with need for post-procedural catheterization in prostate cancer patients treated with 15 Gy high dose-rate brachytherapy boost (HDR-BT). Material and methodsPatients treated with 15 Gy HDR-BT followed by EBRT were retrospectively evaluated for development of urinary retention and hematuria requiring catheterization in the first 30 days post procedure. Clinical characteristics and treatment details were obtained and used as independent variables under study. Univariable and multivariable logistic regression analysis were used to determine predictors of post brachytherapy complications and a classification tree for risk of urinary retention was created using recursive partitioning analysis (RPA). ResultsA total of 425 patients treated with 15 Gy HDR-BT were included in this analysis. 27 patients (6.3%) required catheter placement due to acute urinary retention and thirteen other patients (3%) developed hematuria requiring urinary catheter insertion ± continuous bladder irrigation. Number of needles, prostate volume and prior use of ADT, alpha-blockers or 5α-reductase inhibitors were statistically associated with urinary retention in the univariable logistic regression analysis. In multivariable analysis, prostate volume, previous use of alpha-blocker, and use of ADT remained significant. In the RPA, populations were identified in which the rate of urinary retention ranged from 2% to 50% depending on presence of one or more of these risk factors. ConclusionThe overall rate of acute urinary complications post HDR brachytherapy is low, but the individual risk of urinary retention can increase depending on the number of risk factors present. A more patient-directed retention risk estimation can be performed by using the classification risk tree presented here.

89: Does The Timing of High Dose Rate Brachytherapy Boost in Relation to External Beam Radiation Impact Acute Toxicities in Patients Receiving Combined Modality Radiotherapy for Prostate Cancer?

89: Does The Timing of High Dose Rate Brachytherapy Boost in Relation to External Beam Radiation Impact Acute Toxicities in Patients Receiving Combined Modality Radiotherapy for Prostate Cancer?

21: Comparison of Acute Toxicities in Patients with Prostate Cancer Treated with High Dose Rate Versus Low Dose Rate Brachytherapy Boost

21: Comparison of Acute Toxicities in Patients with Prostate Cancer Treated with High Dose Rate Versus Low Dose Rate Brachytherapy Boost