Fraction High Dose Rate Brachytherapy Research Articles

21 Gy single fraction prostate HDR brachytherapy: 5-year results of a single institution prospective pilot study

PURPOSETo present the outcome and toxicity results of a prospective trial of 21 Gy single fraction high-dose-rate (HDR) brachytherapy for men with low- or intermediate-risk prostate cancer. METHODS AND MATERIALSPatients were treated according to an IRB-approved prospective study of single fraction HDR brachytherapy. Eligible patients had low- or intermediate-risk prostate cancer with tumor stage ≤ T2b, PSA ≤ 15, and Gleason score ≤ 7. Patients underwent trans-rectal ultrasound-guided trans-perineal implant of the prostate followed by single fraction HDR brachytherapy to a dose of 21 Gy. The primary endpoint was grade ≥ 2 urinary/GI toxicity rates. RESULTSTwenty-six patients were enrolled with a median follow up of 5.1 years and median age of 64 years. 88.5% of patients had T1 disease, 15.4% had Gleason score 6 (84.6% Gleason 7), and median pre-treatment PSA was 5.0 ng/mL. Acute and chronic grade ≥ 2 urinary toxicity rates were 38.5% and 38.5%, respectively. There were no grade ≥ 2 acute or chronic GI toxicities. Six (23.1%) patients experienced biochemical failure, six (23.1%) patients experienced radiographic local failure, and five (19.2%) patients had biopsy-proven local failure. No patients developed regional lymph node recurrence or distant metastasis. 5-year overall survival and cause-specific survival were 96.2% and 100%, respectively. CONCLUSIONS21 Gy single fraction HDR brachytherapy was associated with modestly higher-than-anticipated chronic urinary toxicity, as well as high biochemical and local failure rates. The results from this prospective pilot study do not support the use of this regimen in standard clinical practice.

Dosimetric Parameters Predictive of Treatment-Related Toxicity in High Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer.

High dose-rate (HDR) brachytherapy as monotherapy is an effective treatment for patients with low- and intermediate-risk prostate cancer and is increasingly being offered as a 2-fraction protocol. There is a lack of consensus on the optimal dosimetric planning parameters to use, or whether there is any benefit summating dosimetric parameters from more than one implant. Our goal is to determine planning parameters associated with disease control, toxicity and health-related quality of life (HRQOL). Data were collected on 83 patients with low- and intermediate-risk prostate cancer who received 2 fractions of 13.5 Gy HDR brachytherapy without androgen-deprivation therapy as part of a randomized phase II clinical trial. An in-house deformable, registration algorithm was used to co-register and dose-summate the plans from both implants for each patient. Acute and late GU and GI toxicities were measured using CTCAE 4.0 and HRQOL was measured in urinary, bowel, sexual and hormonal domains using the EPIC scores. Treatment efficacy was assessed through PSA measurement and imaging with or without biopsy where indicated. Covariates included baseline clinical factors, disease characteristics and treatment dosimetric parameters. Cox proportional hazards was performed to evaluate covariates impact on treatment toxicity and efficacy, and logistic regression analysis evaluated covariates impact on HRQOL. Among the 83 patients, median prostate volume was 46.7cm3. Median summated planning target volume receiving 100% prescription dose (PTV V100%) was 97.4%, median PTV V150% 42.4% and median PTV V200% 15.5%. Median highest dose to the 1cm3 rectum (D1cc) was 66.9% of the prescription dose and median rectum V80% was 0.008cm3. Median urethral D1cc was 99.0% of the prescription dose, median urethral Dmax 121.7% and median urethral D10% 116.2%. Grade ≥2 GI toxicity was uncommon (3.7% acute and 8.5% late), but grade ≥2 GU toxicity was reported in 73.2% (acute) and 46.3% (late) patients. Rectum D1cc and V80% were found to be significantly associated with grade 2 or higher acute GI toxicity, while use of a-blocker at baseline was associated with grade ≥2 acute GU toxicity. Similarly, use of a-blocker was associated with late grade ≥2 GU toxicity, but with no dosimetric associations. No other variables were associated with treatment-related toxicities. Only rectum D1cc was significantly associated with changes in bowel EPIC scores. Estimated 5-year biochemical disease-free survival was 93.9% and 5-year cumulative incidence of local failure was 3.8%. HDR monotherapy with 27 Gy delivered in 2 fractions in treatment of prostate cancer is well tolerated with high rates of disease control and minimal toxicity. Dose summation between 2 fractions of HDR brachytherapy is feasible, with rectal dose predicting acute GI toxicity. The lack of association between dose metrics and urinary toxicity raises the potential for further dose escalation.

Long-Term Outcomes Associated with Different High-Dose-Rate Brachytherapy Dose Regimens for Favorable and Unfavorable Intermediate Risk Prostate Cancer.

To present long-term efficacy outcomes of prostate high-dose-rate (HDR) brachytherapy monotherapy using 38 Gy in 4 fractions, 24 Gy in 2 fractions, and 27 Gy in 2 fractions for men with favorable and unfavorable intermediate risk prostate cancer. Patients treated with HDR brachytherapy monotherapy for NCCN favorable (FIR) or unfavorable (UIR) intermediate risk prostate cancer from 1999-2020 were identified in a prospectively maintained, single institution database. Patients with less than two years of follow-up and those treated with single fraction HDR brachytherapy were excluded. Biochemical failure was determined using Phoenix criteria. 10-year biochemical control (BC), local control (LC), and distant metastasis (DM) rates were estimated using the Kaplan-Meier method. Two hundred sixty-seven patients were included. One hundred eighty-nine had FIR and 78 had UIR prostate cancer, with median follow-up of 9.6 years and 7.2 years, respectively. Of the 189 patients with FIR prostate cancer, 59 (31.2%) received 38 Gy in 4 fractions, 26 (13.7%) received 24 Gy in 2 fractions, and 104 (55.0%) received 27 Gy in 2 fractions. Of the 78 patients with UIR prostate cancer, 20 (25.6%) received 38 Gy in 4 fractions, 11 (14.1%) received 24 Gy in 2 fractions, and 47 (60.2%) received 27 Gy in 2 fractions. Date ranges of treatment for the respective fractionation schedules were 1999-2010, 2007-2016, and 2009-2020. Upfront androgen deprivation therapy (ADT) was given to 12 (6.3%) patients with FIR and 10 (12.8%) patients with UIR. 10-year rates of BC for FIR and UIR patients were 90.1% and 78.8% (p = 0.004), respectively. 10-year rates of LC were 92.4% and 85.0% (p = 0.06), respectively. 10-year rates of DM were 1.9% and 4.7% (p = 0.12), respectively. For FIR patients, 10-year BC rates were 96.2% for patients receiving 38 Gy in 4 fractions vs. 86.3% (p = 0.07) for those treated with the 2-fraction regimens, while 10-year LC rates were 97.9% and 89.0% (p = 0.049), respectively. Within the UIR subset, the 10-year BC rates for patients receiving 38 Gy in 4 fractions and patients receiving treatment in 2 fractions were 95.0% and 70.6% (p = 0.038). 10-year LC rates were 100% and 77.8% (p = 0.045), respectively. 10-year BC rates by treatment schedule are shown in the table below. HDR brachytherapy monotherapy results in excellent long-term local control for intermediate risk prostate cancer. Improvements in biochemical and local disease control for patients treated with 38 Gy in 4 fractions warrants consideration of prospective study of optimal treatment dosing regimens.

Single Dose vs. Fractionated High-Dose Rate Brachytherapy in Localized Prostate Cancer: Long Term Results

To evaluate long-term freedom from biochemical relapse (FFbR) and overall survival (OS) after single-dose high-dose-rate brachytherapy (HDR-BT) compared with 2 or 3 fraction schedules. HDR-BT, delivering 1 × 19 Gy or 1 × 20 Gy (A = 49), 2 × 13 Gy (B = 138) or 3 × 10.5 Gy (C = 106), was given to patients with intermediate or high-risk prostate cancer as their sole treatment. Patients were staged with pelvic MRI and isotope bone scan. Transperineal transrectal ultrasound guided implantation was followed by MRI based CTV definition based on GEC ESTRO guidelines. Biochemical relapse was assessed using the Phœnix definition (PSA nadir plus 2 µg/L). Patients were evaluated prospectively from 6 months after implant and bi-annually thereafter. Estimates of freedom from biochemical relapse, and overall survival (OS) were calculated using the Kaplan-Meier (K-M) method and the log-rank test to test for significance. Univariate and multivariate hazard ratios (HR) were obtained using Cox's proportional hazard model. For multivariate modelling a stepwise reduction method was used. Median follow-up was 123, 116 and 120 months (p = 0.4), (A, B, C, respectively). Neo-adjuvant and adjuvant androgen deprivation treatment was given to 80% of all patients, median duration was 9 months for A and 6 months for B and C. K-M estimates of FFbR, at 8 and 10 years, were 67% and 64% (Group A), 78% and 72% (Group B), and 80% and 76% (Group C). Differences in FFbR between dose groups was not significant (p = 0.2). Similarly, no significant difference was seen in OS. Eight and 10-year estimates were 81% and 75% (A), 85% and 74% (B), and 90% and 83% (C); p = 0.5. Hazard Ratios for risk of biochemical recurrence were significant for ADT administration (yes/no) and overall risk category, in multivariate analyses. Only the latter was significant in univariate analysis for risk of death, Gleason risk (low, intermediate, high), MRI tumor stage risk and overall risk category were significant in univariate analyses. Only tumor stage and Gleason risk were significant in multivariate analyses. Concerns around the efficacy of 19-20 Gy single dose HDR BT as monotherapy, based on early data, may have been unfounded. Long-term outcome data up to 10 years show no significant difference in PSA control and overall survival compared to 2 and 3 fractions of HDR-BT.

The use of Lutetium-177 PSMA radioligand therapy with high dose rate brachytherapy for locally recurrent prostate cancer after previous definitive radiation therapy: a randomized, single-institution, phase I/II study (ROADSTER).

BackgroundIsolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues.MethodsROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment.DiscussionROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy.Trial registrationNCT05230251 (ClinicalTrials.gov).

Dose Distribution of High Dose-Rate and Low Dose-Rate Prostate Brachytherapy at Different Intervals—Impact of a Hydrogel Spacer and Prostate Volume

The study aimed to compare the dose distribution in permanent low-dose-rate brachytherapy (LDR-BT) and high-dose-rate brachytherapy (HDR-BT), specifically focusing on the impact of a spacer and prostate volume. The relative dose distribution of 102 LDR-BT patients (prescription dose 145 Gy) at different intervals was compared with the dose distribution of 105 HDR-BT patients (232 HDR-BT fractions with prescription doses of 9 Gy, n = 151, or 11.5 Gy, n = 81). A hydrogel spacer (10 mL) was only injected before HDR-BT. For the analysis of dose coverage outside the prostate, a 5 mm margin was added to the prostate volume (PV+). Prostate V100 and D90 of HDR-BT and LDR-BT at different intervals were comparable. HDR-BT was characterized by a considerably more homogenous dose distribution and lower doses to the urethra. The minimum dose in 90% of PV+ was higher for larger prostates. As a consequence of the hydrogel spacer in HDR-BT patients, the intraoperative dose at the rectum was considerably lower, especially in smaller prostates. However, prostate volume dose coverage was not improved. The dosimetric results well explain clinical differences between these techniques reported in the literature review, specifically comparable tumor control, higher acute urinary toxicity rates in LDR-BT in comparison to HDR-BT, decreased rectal toxicity after spacer placement, and improved tumor control after HDR-BT in larger prostate volumes.

PP05 Presentation Time: 9:40 AM: 21 Gy Single Fraction Prostate HDR Brachytherapy: Mature Results of a Single Institution Prospective Study.

<h3>Purpose</h3> To present the outcome and toxicity results of a prospective trial of 21 Gy single fraction high-dose-rate (HDR) brachytherapy for men with low- or intermediate-risk prostate cancer. <h3>Materials and Methods</h3> Patients were treated according to an IRB-approved prospective study of single fraction HDR brachytherapy. All patients had low- or intermediate-risk prostate cancer with tumor stage ≤ T2b, PSA ≤ 15, and Gleason score ≤ 7. Patients with prostate volumes > 50 cc or <12 cc, taking alpha-blockers for urinary symptoms, or with baseline American Urologic Association (AUA) symptom scores > 12 were ineligible. Patients underwent trans-rectal ultrasound (TRUS)-guided trans-perineal implant of the prostate followed by single fraction HDR brachytherapy. Treatment was delivered via Ir-192 to a dose of 21 Gy, prescribed to the prostate with no additional margin applied. Treatment planning was TRUS-based with constraints as follows: prostate V100 > 95%; urethral V115 < 1%; rectal V72 ≤ 1% prescription dose. <h3>Results</h3> A total of 26 patients were enrolled. Median follow up was 4.0 years (range 0.6-5.7 years). Median age was 64 years. Median gland volume at the time of treatment was 41 cc. 88.5% of patients had T1 disease, 15.4% had Gleason score 6, 84.6% Gleason score 7, and median pre-treatment PSA was 5.0 (range 2.7-12.2) ng/mL. Acute and chronic grade 2 GU toxicity rates were 26.9% and 38.5%, respectively. Acute grade 3 GU toxicity rate was 11.5%. There were no chronic grade 3 GU toxicities. There were no grade 2+ acute or chronic GI toxicities. The 5-year biochemical failure rate was 35.1%. The 5-year radiographic local failure rate was 32.4%. Biopsy-proven local failure at 5-years was 15.3%. Two patients underwent salvage treatment after experiencing radiographic local failure, without an attempted biopsy of the prostate. No patients developed biopsy proven or radiographic regional lymph node recurrence or distant metastasis. 5-year overall survival was 96.2%. The single patient death was a result of a myocardial infarction approximately 7 months after protocol treatment. Cause-specific survival at 5 years was 100%. <h3>Conclusions</h3> Despite being well-tolerated, 21 Gy single fraction HDR brachytherapy is associated with high biochemical and local failure rates. The results from this prospective pilot study do not support continued investigation of this dosing regimen in subsequent investigation.

PO05: Single Fraction High-Dose-Rate Brachytherapy: A Scoping Review on Outcomes and Toxicities for All Disease Sites

<h3>Purpose</h3> There is increasing interest in single fraction treatments in radiation oncology to improve efficiency and lower costs. Brachytherapy is well positioned to safely deliver highly conformal single fraction doses of radiation. Low-dose-rate brachytherapy has the advantage of being delivered in a single treatment, but high-dose-rate brachytherapy (HDR) has more traditionally been delivered over multiple treatments. Expanding single fraction HDR treatments could be a significant area of growth. A scoping literature review was conducted to better understand the available literature on single fraction HDR for all disease sites. <h3>Materials and Methods</h3> The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The PubMed database was queried from 1994-2021 using the search terms: "brachytherapy", "high-dose-rate", and "single fraction". Included studies were limited to single fraction HDR. Studies that involved the same cohort, follow up less than 1 year, sample size <10 patients, review articles, and case reports were excluded, which resulted in 51 included studies. <h3>Results</h3> Liver had the highest number of studies with 18 (7 primary, 11 metastasis) and included reported outcomes on a total of 618 patients. Single fraction doses ranged from 10-25 Gy. Median follow-up ranged from 11-33 months. Local control rates ranged from 37-98%. Grade 3 or higher toxicities in the acute/late setting were reported in 3 patients in only 1 study.Prostate cancer had the second highest number of studies with 16 (14 definitive, 2 salvage) and included reported outcomes on a total of 1474 patients. Single fraction doses ranged from 19-21 Gy. Median follow-up ranged from 20-72 months. PSA control outcomes after definitive treatment ranged from 65-94% and salvage treatments from 5-84%. Grade 3 or higher toxicities in the acute/late setting ranged from 0-6%. Breast cancer had the third highest number of studies with 7 and included reported outcomes on a total of 268 patients. Single fraction doses ranged from 16-20 Gy. Median follow-up ranged from 24-72 months. Local control rates were 100%. Grade 3 or higher toxicities in the acute/late setting ranged from 0-6%. The remaining 10 studies included the following sites: 4 gastrointestinal, 2 lung, 2 head and neck, 1 glioma, and 1 endometrial. Conclusions from these studies are limited given the small number of patients treated within each respective disease site. <h3>Conclusions</h3> There is a medium sized body of literature using single fraction HDR. Currently used regimens appear safe but efficacy appears to vary by different disease sites. Outcomes are more promising for breast and liver while are less encouraging for prostate. Additional prospective evaluation of single fraction HDR regimens are warranted in disease sites outside of prostate cancer.

Single Fraction HDR Brachytherapy for Prostate Cancer: SiFEPI Phase II Trial Results

<h3>Purpose/Objective(s)</h3> To report the results of the <i>Single Fraction Early Prostate Irradiation</i> (SiFEPI) phase 2 prospective trial. <h3>Materials/Methods</h3> The SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and low-intermediate (LIR) risk prostate cancers. After injection of 10 ml of macromolecular hyaluronic acid (rectal spacer), needles were implanted under endorectal ultrasound guidance. After post-implant CT scan, a single fraction of 20 Gy was delivered to the prostate taking into account the dose constraints for CTV and organs at risk (urethra, rectum, anus). Oncological outcome (biochemical (bRFS), local (lRFS), and metastatic (mRFS) relapses and disease-free (DFS), cause-specific (CSS) and overall (OS) survivals), toxicity profile (acute [d30, d90, d180] and late [> 6 months] genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities) were investigated as well as quality of life (QLQ-C30 and QLQ-PR25). <h3>Results</h3> From March 2014 to October 2017, 35 pts were enrolled. Among them, 33 were evaluable. With a median age of 66 y [46 - 79], 25 (76%) and 8 (24%) pts were LR and FIR respectively. Median MRI prostatic volume was 41 cc [19 - 84]. Median peak-urinary flow and post-void residual volume were 17 ml/s [8 - 25] and 19 cc [0 - 165] while 30 pts (91%) had an IIEF score between 16 and 25. Median CTV, D90% and V100% were 50 cc [29 - 92], 106% [104 - 109], and 98% [96 - 99] respectively. With a MFU of 72.8 months [64 - 86], 6y-bRFS, lRFS and mRFS were 62% [45 - 85], 61% [44 - 85] and 93% [85 - 100] respectively while 6y-DFS, CSS and OS were 54% [37 - 77], 100% and 89% [77 - 100]. Acute GU, GI and S toxicities were observed in 27 pts (82%; 36 G1 & 8 G2), 5 pts (15%; 7 G1 & 3 G2) and 5 pts (15%; 3 G1 & 2 G2) respectively and no acute G3 toxicity was observed. Late GU, GI and S toxicities were observed in 11 pts (33%; 18 G1), 4 pts (12%; 4 G1) and 7 pts (21%; 1 G1, 5 G2 & 1 G3) respectively. QLQ-C30 and QLQ-PR25 will be reported later. Biochemical relapse (BR) was observed in 11 pts (33%; 7 LR & 4 FIR) with a median time interval between HDB and BR of 51 months [24 – 69]. Among them, 9 pts (82%) presented a histologically proven isolated local recurrence and underwent salvage prostate re-irradiation delivering a median dose of 78 Gy [73 – 78] (2 Gy/f). With a MFU from salvage EBRT of 27 months [3 – 59], 2^nd bRFS rate was 100%. One pt presented a G3 GU toxicity (hematuria) while no G≥3 GI complication was observed. <h3>Conclusion</h3> Long-term results of the SiFEPI phase 2 prospective trial showed that a single fraction of 20 Gy (HDB) leads to a sub-optimal biochemical control for LR and LIR prostate cancers. The reported oncological outcome is in line with the previous series of HDB single fraction protocols. However, late GU and GI toxicity profile is encouraging (especially compared to iodine implant series), leading to consideration of HDB as a safe irradiation technique. Salvage EBRT appears feasible with an acceptable risk of complications.

Single fraction of HDR brachytherapy for prostate cancer: Results of the SiFEPI phase II prospective trial

PurposeTo report the results of the Single Fraction Early Prostate Irradiation (SiFEPI) phase 2 prospective trial. Materials/MethodsThe SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and favorable-intermediate (FIR) risk prostate cancers. After rectal spacer placement, a single fraction of 20 Gy was delivered to the prostate. Oncological outcome (biochemical (bRFS) and local (lRFS) relapses, disease-free (DFS) and overall (OS) survivals and toxicity (acute/late genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities were investigated. ResultsFrom 03/2014 to 10/2017, 35 pts were enrolled, of whom 33 were evaluable. With a median age of 66 y [46–79], 25 (76 %) and 8 (24 %) pts were LR and FIR respectively. With a MFU of 72.8 months [64–86], 6y-bRFS, lRFS and mRFS were 62 % [45–85], 61 % [44–85] and 93 % [85–100] respectively while 6y-DFS, CSS and OS were 54 % [37–77], 100 % and 89 % [77–100] respectively. Late GU, GI and S toxicities were observed in 11 pts (33 %;18G1), 4 pts (12 %;4G1) and 7 pts (21 %;1G1,5G2,1G3) respectively. Biochemical relapse (BR) was observed in 11 pts (33 %;7LR,4FIR) with a median time interval between HDB and BR of 51 months [24–69]. Nine of these pts (82 %) presented a histologically proven isolated local recurrence. ConclusionsLong-term results of the SiFEPI trial show that a single fraction of 20 Gy leads to sub-optimal biochemical control for LR/FIR prostate cancers. The late GU and GI toxicity profile is encouraging, leading to consideration of HDB as a safe irradiation technique.

The Experience of Pain and Anxiety in Cervical Cancer Patients Undergoing Multiple Fraction High-Dose Rate Brachytherapy: A Prospective Observational Study

Purpose: To evaluate the anxiety and pain levels of cervical cancer patients undergoing intracavitary multifraction high-dose rate (HDR) brachytherapy, as part of a process to develop guidelines for quality patient-centered care. Methods: Cervical cancer patients (n = 31) undergoingmultiple fraction HDR brachytherapy treatment at the National Institute of Oncology in Rabat (Morocco) completed ratings of pain and anxiety intensity using 11-point verbal analog scales, at 6 key time points over 2 brachytherapy insertion procedures and 4 brachytherapy fractions. Women were evaluated for psychological status at baseline before starting the brachytherapy process using the Hospital Anxiety and Depression Scale (HADS). Scores were grouped as follows: 0 - 7 = normal, 8 - 10 = borderline, 11 - 21 = abnormal. Factors that could affect anxiety levels such as education level, relationship status, number of pregnancies and prior surgical history were documented. Results: Between July and August 2020, 31 women with a median age of 49.6 years were evaluated (range: 27 - 70). The HADS score identified depression in 5 patients (16.1%) and anxiety in 12 patients (38.7%). Throughout both treatment procedures, anticipatory anxiety was reported, with a maximum intensity in the operating room during spinal anesthesia (3.23 ± 1.7) and during applicator insertion (2.97 ± 2.4). Moderate-to-severe anxiety scores were reported in 25.8% and 22.6% of patients respectively. Level of education showed a significant correlation with anxiety scores (p = 0.027). Pain increased significantly during the procedure (p ± 1.4) and applicator removal (4.74 ± 1.5) turned out to be the most painful parts of the procedure. No correlation was found between pain and anxiety levels. Conclusion: Intracavitary multifraction high-dose rate brachytherapy is associated with mild to moderate levels of pain and anxiety, although a subset of patients reported more severe symptoms and may require additional medical and psychological support, with particular emphasis on bed-rest duration and applicator removal. The development of effective interventions (both pharmacological and non-pharmacological) is needed to improve women’s experiences of brachytherapy for locally advanced cervical cancer.

Dosimetric Predictors of Toxicity and Quality of Life Following Single Fraction High Dose-Rate Prostate Brachytherapy

<h3>Purpose/Objective(s)</h3> Little is known about optimal dose constraints when high dose rate (HDR) brachytherapy is used as monotherapy for prostate cancer. Most dose constraints for HDR monotherapy were extrapolated from predictors of toxicity when HDR brachytherapy was combined with external beam radiotherapy as a boost. We sought to determine clinical and dosimetric predictors of toxicity and health related quality of life (HRQOL) in men treated with HDR brachytherapy as monotherapy. <h3>Materials/Methods</h3> Eligible patients were treated with single fraction HDR brachytherapy as monotherapy on two prospective clinical trials at a single institution. Patients in the first trial (HDR-mono) received a single fraction of 19 Gy without a dominant intraprostatic lesion (DIL) boost, and patients from the second trial (MARS) received 19 Gy in a single fraction with an MRI-guided DIL boost to ≥ 23 Gy. ADT was not used. Univariable and multivariable logistic regression was used to evaluate clinical (age, IPSS score, prostate volume, alpha blocker use at baseline, and receipt of a DIL boost) and dosimetric (prostate V100, V150, V200, D90, Urethral Dmax and D10, and Rectal Dmax and V80) predictors of CTCAE v4 acute/late toxicity and HRQOL changes measured with expanded prostate index composite (EPIC). Three classifications of late minimally clinically important changes (MCICs) were evaluated: small (> 0.5 standard deviation [SD]), moderate (> 1.0 SD) and severe (> 2.0 SD) declines compared to baseline. <h3>Results</h3> 147 patients were included (87 from HDR-mono, 60 from MARS). Median follow-up was 62.8 months. Only increasing prostate size predicted acute GU toxicity ≥ grade 2 (OR 1.05, 95% CI 1.01–1.09, <i>P</i> = 0.021). On multivariable regression, predictors of late GU toxicity ≥ grade 2 were not receiving a DIL boost (OR 3.78, 95% CI 1.88–7.83, <i>P</i> < 0.001) and higher baseline IPSS score (OR 1.89, 95% CI 1.89–3.18, <i>P</i> = 0.015). Rectal and urethral dose constraints were not associated with late GU/GI toxicity ≥ grade 2. Contrary to our hypothesis, small (OR 0.91, 95% CI 0.81–0.98, <i>P</i> = 0.032) and moderate (OR 0.91, 95% CI 0.80–0.98, <i>P</i> = 0.037) urinary MCICs were less frequent in those with higher urethral Dmax. No impact of urethra D10 on urinary MCICs was seen. Rectal Dmax and V80 did not predict bowel MCIC changes at any threshold. <h3>Conclusion</h3> We were unable to identify dose constraints that were predictive of late toxicity or relevant HRQOL changes in single fraction HDR brachytherapy. This suggests dose parameters used in these trials were safe, and that minor variability in plan dosimetry likely has little clinical significance. While increasing urethral Dmax paradoxically predicted for less frequent urinary MCICs, we do not believe this finding is clinically relevant. Further research exploring optimal dose constraints to be used in HDR brachytherapy as monotherapy for prostate cancer is warranted.

Demographic and clinical factors associated with variations in opioid administration using conscious sedation during HDR brachytherapy for cervical cancer

PURPOSE/OBJECTIVES To examine patient characteristics that predispose to higher opioid administration during tandem and ovoid (T&O) high-dose rate (HDR) brachytherapy. METHODS A single-institution retrospective review was performed on patients who underwent brachytherapy for cervical cancer. Patients were included if they received at least one fraction of HDR T&O brachytherapy with analgesia administration recorded in the Medication Administration Record. Fentanyl dose was dichotomized as "low" (mean <125 μg per fraction), or "high" (mean ≥ 125 μg per fraction). Descriptive statistics and multiple logistic regression analysis were performed comparing mean opioid dose per fraction with demographic and clinical information. RESULTS From July 2014 through May 2020, 113 patients underwent 531 T&O HDR brachytherapy fractions with oral benzodiazepine and intravenous opioid fentanyl for conscious sedation. The median opioid dose per fraction was 100 μg fentanyl (range 0-250 μg). Using multiple logistic regression analysis, younger age (OR 1.071, p = 0.002) and higher BMI (OR 1.091, p = 0.019) were associated with increased opioid administration during brachytherapy. Black women received less opioid during brachytherapy when compared to White women (OR 0.296, p = 0.047). FIGO stage, ECOG score, smoking status, prior narcotic use, prior illicit drug use, parity, prior cervical procedure, Smit sleeve placement, and distance to treatment center were not associated with high opioid dose. CONCLUSION Cervical cancer patients who are younger or have higher BMI receive more narcotic analgesia during HDR brachytherapy whereas Black women received less narcotic analgesia, irrespective of age and BMI. This underscores the immediate need to address how pain is assessed and managed during brachytherapy.

PO41: 21 Gy Single Fraction High Dose Rate Brachytherapy for Early Stage Prostate Cancer: Early Outcomes from a Single Institution Prospective Clinical Trial

PO41: 21 Gy Single Fraction High Dose Rate Brachytherapy for Early Stage Prostate Cancer: Early Outcomes from a Single Institution Prospective Clinical Trial

PO41: 21 Gy Single Fraction High Dose Rate Brachytherapy for Early Stage Prostate Cancer: Early Outcomes from a Single Institution Prospective Clinical Trial

Purpose: Previous reports investigating single fraction high dose rate (HDR) brachytherapy as monotherapy for localized prostate cancer have reported favorable toxicity profiles but higher than expected local failure rates. This analysis reports outcomes of a series of patients treated with single fraction HDR brachytherapy to an escalated whole gland dose of 21 Gy.

Single dose high-dose-rate brachytherapy with focal dose escalation for prostate cancer: Mature results of a phase 2 clinical trial

AimThe dominant intraprostatic lesion (DIL) is the commonest site of relapse after single dose high-dose-rate brachytherapy (HDR-BT) for localised prostate cancer. This study investigated toxicity and clinical outcomes of focal dose escalation to the DIL with dose de-escalation to the remaining prostate. Materials/MethodsBetween November 2012 and July 2016, 50 patients with localised prostate adenocarcinoma received single fraction HDR-BT. 21 Gy was prescribed to the DIL, with two de-escalation prescription schedules for the remaining prostate. Primary outcomes included biochemical no evidence of disease (bNED), local recurrence free survival (LRFS), and metastasis free survival (MFS). Secondary outcomes included late genitourinary, gastrointestinal and sexual toxicity. Kaplan—Meier analyses with log rank tests were used to estimate bNED, LRFS and MFS. ResultsWith a median follow up of 70.6 months, 15 patients developed biochemical failure, including 8 in the group that received minor dose de-escalation to the non-DIL prostate (group 1) and 7 in the group that received moderate de-escalation (group 2). Five-year bNED was 88% in group 1 and 76% in group 2 (p = 0.05). Overall 4-year and 5-year FFLF in group 1 was 100% and 96% and in group 2 92% and 84%. These differences were statistically significant (p = 0.03). No acute ≥G3 genitourinary or ≥G2 gastrointestinal toxicity was reported. The median IIEF decreased in the first 6 months improving to a peak median score of 20 at 54 months. ConclusionFocal boost to the DIL did not improve biochemical or local control after single-fraction HDR monotherapy compared to what would be expected from 19 Gy single fraction treatment to the whole gland.

High dose rate intra-cavitary brachytherapy with cobalt 60 source for locally advanced cervical cancer: the Zimbabwean experience

Background and purposeCervical cancer is the fourth commonest cancer in women in the world with the highest regional incidence and mortality seen in Southern, Eastern and Western Africa. It is the commonest cause of cancer morbidity and mortality among Zimbabwean women. Most patients present with locally advanced disease that is no longer amenable to surgery. Definitive concurrent chemoradiation (CCRT), which is the use of external beam radiotherapy (EBRT) and weekly cisplatin, includes use of intracavitary brachytherapy, as the standard treatment. In the setting of this study, cobalt-60 (Co60)-based high dose rate brachytherapy (HDR-BT) has been in use since 2013. This study sought to review practices pertaining to use of brachytherapy in Zimbabwe, including timing with external beam radiotherapy, adverse effects and patient outcomes.MethodsA retrospective analysis of data from records of patients with histologically confirmed cervical cancer treated with HDR-BT at the main radiotherapy centre in Zimbabwe from January 2013 to December 2014 was done. Outcome measures were local control, overall survival as well as gastro-intestinal and genito-urinary toxicity.ResultsA total of 226 patients were treated with HDR-BT during the study period, with a 97% treatment completion rate. All patients received between 45-50Gy of pelvic EBRT. Seventy-four percent received concurrent platinum-based chemotherapy. In 52% of the patients, HDR-BT was started when they were still receiving EBRT. The commonest fractionation schedule used was the 7Gy × 3 fractions, once a week (87%). Clinical complete tumour response was achieved in 75% at 6 weeks post treatment, 23% had partial response. Follow-up rates at 1 year and 2 years were 40 and 19% respectively. Disease free survival at 1 year and 2 years was 94 and 95% respectively. Vaginal stenosis was the commonest toxicity recorded, high incidence noted with increasing age. Four patients developed vesico-vaginal fistulae and two patients had rectovaginal fistulae.ConclusionOne hundred and seventeen patients patients started HDR-BT during EBRT course, with a treatment completion rate of 97%. The overall treatment duration was within 56 days in the majority of patients. Early local tumour control was similar for all the HDR-BT fractionation regimes used in the study, with a high rate (75%) of complete clinical response at 6 weeks post-treatment. Prospective studies to evaluate early and long-term outcomes of HDR-BT in our setting are recommended.

Salvage brachytherapy for locally recurrent prostate cancer after single-fraction 19 Gy high-dose-rate brachytherapy: toxicity, prostate-specific antigen kinetics, and cancer control.

PurposeTo evaluate toxicity, prostate-specific antigen (PSA) kinetics, and cancer control of high-dose-rate brachytherapy (HDR-BT) as a salvage modality for men with locally recurrent prostate cancer, after primary HDR-BT failure.Material and methodsTwelve patients with biochemical failure and a local relapse after 19 Gy single-fraction high-dose-rate brachytherapy (HDR-BT 19 Gy) were salvaged using two HDR-BT fractions. Salvage treatment consisted of two HDR-BT applications, one week apart, delivering 12 Gy to the prostate per application (HDR-BT 12 × 2).ResultsMedian age and initial PSA prior to rescue treatment were 74 years (range, 65-80) and 5.29 ng/ml (range, 2.37-16.40), respectively. Forty-two percent had a low-risk and 58% presented with intermediate-risk prostate cancer. Median follow-up period was 26 months (range, 10-42). Median time to PSA nadir was 12 months, with a median value of 0.21 ng/ml. Most of the patients (11 of 12) achieved a PSA decline ≥ 90%. Acute grade 2 genitourinary (GU) toxicity occurred in 4 patients (33.3%) and none presented with acute gastrointestinal (GI) toxicity. Two patients (16.7%) suffered from late GU grade 2 toxicity. No grade 3 toxicity were recorded. To date, 2 patients (16.7%) have experienced biochemical failure after salvage treatment.ConclusionsSalvage HDR-BT 12 × 2 is a feasible and well-tolerated treatment, with acceptable toxicity rates for men with locally recurrent prostate cancer, who failed after HDR-BT with 19 Gy. Moreover, PSA kinetics and cancer control after salvage treatment suggest that this strategy might be efficacious in this clinical setting.

Acute Toxicity and Local Response using Three Fractions of High Dose Rate (HDR) Brachytherapy for Curative Treatment of Carcinoma Cervix.

Descriptive study. Radiation Oncology Section, Department of Oncology, The Aga Khan University Hospital, Karachi, Pakistan from January 2008 till December 2015. Protocol was formulated for carcinoma cervix to complete treatment in 7 weeks. Patients were treated with chemotherapy and pelvic EBRT to a total dose of 45 Gy/25 fractions, followed by three intracavitary HDR brachytherapy fractions of 8 Gy each. Vaginal toxicity and local clinical response was assessed at the end of treatment, at 4 and 8 weeks. A total of 57 patients were treated with HDR brachytherapy and 49 patients were evaluated for assessment of toxicity and response. According to FIGO staging system, two had stage IB2, one had IIA, thirty-six had IIB, seven had IIIB, one had IVA disease and two had IVB with para aortic nodes. Concurrent gemcitabine and cisplatin were given to 26 (46%); whereas, 28 (49%) received concurrent cisplatin alone. Grade III acute vaginal mucosal toxicity was seen in 52 and Grade IV acute vaginal mucosal toxicity was observed in 08 patients. At completion of treatment, 40 patients had complete clinical response, at 4 weeks follow-up, complete regression of disease was found in 3 more and at 8 weeks none had clinical residual disease. This regimen of HDR brachytherapy treatments is feasible, efficacious, and well-tolerated for carcinoma cervix in a setup with cost constraints. Long term toxicity and disease control remains to be reported with longer follow-up. Key Words: Carcinoma cervix, High dose rate brachytherapy, Acute toxicity, Local response, External beam radiation therapy, Intracavitary brachytherapy.

Efficacy and toxicity outcomes for patients treated with focal salvage high dose rate brachytherapy for locally recurrent prostate cancer

IntroductionIsolated local recurrence of prostate cancer following primary radiotherapy or brachytherapy may be treated with focal salvage high dose rate brachytherapy, although there remains an absence of high quality evidence to support this approach. MethodsMen with prostate cancer treated consecutively between 2015 and 2018 using 19 Gy in a single fraction high dose rate brachytherapy (HDR) for locally recurrent prostate cancer were identified from an institutional database. Univariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS). Results43 patients were eligible for evaluation. Median follow up duration was 26 months (range 1–60). Median bPFS was 35 months (95% confidence interval 25.6–44.4). Kaplan-Meier estimates for bPFS at 1, 2 and 3 years post salvage were 95.2%, 70.6% and 41.8% respectively. On univariable Cox regression analysis, only nadir PSA was significantly associated with bPFS although the majority of patients were also treated with androgen deprivation therapy. Only one late grade 3 genitourinary toxicity was observed. ConclusionFocal salvage HDR brachytherapy may provide good biochemical control with a low risk of severe toxicity. Further evaluation within clinical trials are needed to establish its role in the management of locally recurrent prostate cancer.