Francois Bachand

Skin dose in breast brachytherapy: Defining a robust metric

PURPOSE To define a simple, robust, and relevant metric for measuring skin dose in breast brachytherapy. METHODS AND MATERIALS Postoperative treatment plans (Day 0) for 15 permanent breast seed implant (PBSI) and 10 multicatheter high-dose-rate (MC-HDR) brachytherapy patients were included. Retrospectively, three skin structures were contoured: 2 mm external from the body; and subsurface layers 2 mm and 4 mm thick. Maximum point dose (Dmax), doses to small volumes (e.g., D0.2cc), and the volumes receiving a percentage of the prescription dose (V%, e.g., V66) were calculated. D0.2cc was investigated as a surrogate to the dose given to 1 cm(2) of skin (D1cm(2)). Pearson product-moment correlation (R(2)) was computed between metrics. RESULTS Observed trends were consistent across brachytherapy technique. V% did not correlate well with any other metrics: median (range) R(2), 0.63 (0.43, 0.77) and 0.69 (0.3, 0.89) for PBSI and MC-HDR, respectively. Dmax was inconsistently correlated across contours and not well correlated with doses to small volumes: median (range) R(2), 0.85 (0.76, 0.93) and 0.88 (0.83, 0.93) for PBSI and MC-HDR, respectively. In contrast, doses to small volumes were consistently well correlated, even across skin layers: D0.1cc vs. D0.2cc median (range) R(2), 0.98 (0.97, 0.99) and 0.97 (0.94, 0.99) for PBSI and MC-HDR, respectively. CONCLUSIONS Doses to small volumes are robust measures of breast skin dose and given skins strong area effect, D0.2cc for a 2 mm thick skin layer, a simple surrogate of D1cm(2), is recommended for recording skin dose in any breast brachytherapy. Dmax is not robust and should be avoided.

A population-based study of the use of radium 223 in metastatic castration-resistant prostate cancer: Factors associated with treatment completion

INTRODUCTION Radium 223 (Ra223) given for six cycles has proven efficacy in clinical trials, but its population-level generalizability has not been well-described. The objectives of this study were to describe population-based Ra223 use in the abiraterone and enzalutamide era and identify factors associated with completion. METHODS All Ra223 patients at the British Columbia Cancer Agency between September 2013 and February 2016 were identified. Patients who completed <5 vs. ≥5 cycles were compared on patient characteristics, lines of prior therapy, prostate-specific antigen (PSA) and alkaline phosphatase (ALP) decline >30% from baseline (R30%), and survival, to identify factors associated with therapy completion. RESULTS Ninety-one patients were identified; 48 (52.7%) completed >5 cycles. Median overall survival (mOS) was 10.7 months, PSA and ALP R30% were 21% and 52%, respectively. Completion of <5 cycles was associated with higher baseline ALP (p=0.05) and lower baseline hemoglobin (Hb) levels (p=0.03). Patients in the ≥5 cycles group had longer mOS than those in the <5 cycles group (16.2 vs. 5.9 months; p<0.0001), as well as higher PSA R30% (33.3% vs. 7.0%; p=0.002) and ALP R30% (66.7% vs. 34.9%; p=0.03). Patients with ALP ≥220 and Hb ≤118 had 3.85 times the odds of not completing ≥5 cycles vs. ALP <220 and Hb >118. CONCLUSIONS Compared to clinical trials, patients in a population-based setting had more lines of therapy and shorter survival. Lower ALP and higher hemoglobin were associated with completion of >5 cycles, longer mOS, and greater incidence of PSA and ALP response.

Long-Term Prostate Specific Antigen Stability and Predictive Factors of Failure after Permanent Seed Prostate Brachytherapy

Purpose Defining biochemical failure as nadir + 2 may overestimate cure after radiotherapy. We assessed long‐term prostate specific antigen stability after low dose rate prostate brachytherapy and predictors of biochemical failure when prostate specific antigen was slowly rising below the nadir + 2 ng/ml threshold. Materials and Methods A total of 2,339 patients with low or intermediate risk prostate cancer received 125iodine brachytherapy from 1998 to 2010 with a minimum 3‐year followup. In addition, 49.7% of the patients received 6 months of androgen deprivation. Clinical, dosimetric and prostate specific antigen data were retrieved from a prospective database. Biochemical results were classified as stable or rising prostate specific antigen (0.2 ng/ml or greater and increased 0.1 ng/ml or greater during the preceding 2 years), or biochemical failure (defined as nadir + 2). Multivariate analysis was done to identify predictors of failure used to create logistic regression models. Results At a median followup of 89 months (range 37 to 199) prostate specific antigen was stable (nadir 0.03 ng/ml and at 60 months 0.04 ng/ml) in 2,004 patients (86%) and rising (nadir 0.16 ng/ml and at 60 months 0.29 ng/ml) in 145 (6%) while biochemical failure (nadir 0.51 ng/ml, p <0.001) was noted in 190 (8%). When there was no prior androgen deprivation therapy, the prostate specific antigen nadir and prostate specific antigen at 60 months were the strongest predictors of failure (OR 20.6 and 18.3, respectively, each p <0.0001). The logistic regression model had 85% sensitivity and 98% specificity, and predicted failure in 8 of 82 men (9.8%). A second model was created for the group with androgen deprivation therapy and rising prostate specific antigen using the predictive factors prostate specific antigen at 60 months (OR 53.9, p <0.0001) and T stage (OR 0.25, p = 0.0008). This model predicted biochemical failure in 30 of 56 men (54%) with 85% sensitivity and 93% specificity. The 2 predictive models yield an anticipated 90% cure rate in the entire cohort. Conclusions Brachytherapy is highly curative with stable prostate specific antigen at a surgical ablation level in 86% of patients. Rising prostate specific antigen is rare at a 6% incidence and often innocuous.

A Phase II trial of 8 weeks of degarelix for prostate volume reduction: Efficacy and hormonal recovery

PURPOSE The purpose of this study was to determine the efficacy of 8 weeks of degarelix for prostate downsizing before interstitial brachytherapy. We also report associated toxicity and the time course of endocrine recovery over the following 12 months. METHODS AND MATERIALS Fifty patients were accrued to an open-label Phase II clinical trial (www.clinicaltrials.gov ID NCT01446991). Baseline prostate transrectal ultrasound (TRUS) was performed on all patients followed by degarelix administration and a repeat TRUS at Week 8. Brachytherapy was performed within 4 weeks of the 8-week TRUS for all patients who achieved suitable downsizing. RESULTS The median prostate volume was reduced from 65.0 cc (interquartile range [IQR]: 55.2-80.0 cc) to 48.2 cc at 8 weeks (IQR: 41.2-59.3 cc), representing a median decrease of 26.2% (IQR: 21-31%). Functional recovery of testosterone within an age-adjusted normal range occurred at a median of 34.1 weeks (IQR: 28.2-44.5 weeks) from the date of the final injection. Despite this recovery, follicle-stimulating hormone and luteinizing hormone levels remained abnormally elevated throughout 12 months. Quality-of-life implications are discussed. CONCLUSIONS Degarelix is effective for prostate downsizing before prostate brachytherapy with a median volume decrease of 26.2% by 8 weeks. Despite the short course of treatment and eventual testosterone recovery, follicle-stimulating hormone and luteinizing hormone remain elevated beyond 12 months. Further investigation with randomized comparisons to other hormonal agents is warranted.

15: Feasibility of Collecting Patient Reported Outcomes for Patients Receiving Curative Intent RT for Gynecological Malignancies

CARO 2016 _________________________________________________________________________________________________________ was sent to all 14 provincial cancer centres in 2013. The survey included 72 questions in four different categories: general/demographic, pre-treatment assessment, EBRT and BT questions. Results: The response rate was 100%. Ten out of 14 centres treated cervical cancer patients and had a dedicated brachytherapy suite. All 10 centres that treated cervix cancer had a peer review process for quality assurance (QA). Nine centres had written treatment planning and delivery protocol and five centres used a specific plan evaluation protocol for organs at risk for EBRT. The standard EBRT technique was 4-field box in eight centres and one centre used IMRT if treating the para-aortic nodes simultaneously; one centre did not respond. The dose/fractionation scheme to the whole pelvis was 45-50 Gy in 1.8-2 Gy per fraction in all but one centre. Nine centres used image verification at some point during EBRT. All ten centres used HDR brachytherapy and one centre also used PDR brachytherapy to treat cervix cancer patients. Brachytherapy was performed under general anesthesia, regional anesthesia and conscious sedation in four, one and five centres, respectively. Only one centre offered interstitial brachytherapy. The majority of centres (eight of 10) used ultrasound image guidance for intrauterine applicator insertion. For treatment planning two centres used CT and MRI, four centres used CT only and four centres used orthogonal x-rays. GEC-ESTRO guidelines were used in three centres for target volume delineation and in five centres for organs at risk (OAR) dose constraints. Nine centres prescribed and reported dose to Point A. Volumetric dose prescription was performed in one centre and four centres reported dose to a target volume. Eight centres reported dose to OARs. The number of BT applicator insertions varied significantly between the centres ranging from one to six. The dose prescription was also variable ranging from 5.5 Gy to 8 Gy per fraction. Conclusions: The main findings from the survey were the variation in the BT dose fractionation and treatment planning used in the regional cancer centres while there was a general uniformity in peer reviewed QA, written institutional treatment protocol, EBRT technique, dose fractionation scheme and use of HDR BT across the province. This study shed light on the need to implement a harmonized evidence-based brachytherapy practice for cervical cancer in order to improve patients’ outcome across Ontario, Canada.

Grade 3 Radiation Recall Sigmoiditis after Treatment for Locally Advanced Cervical Cancer: A Case Report.

We report a case of Grade 3 radiation recall sigmoiditis after administration of a combination of carboplatin, paclitaxel, and bevacizumab, following irradiation for a locally advanced cervical cancer. A 50-year-old woman was diagnosed with an FIGO Stage IIIb squamous cell carcinoma of the cervix with bilateral pelvic and para-aortic lymph nodes. She underwent concurrent chemoradiation followed by high dose rate (HDR) intracavitary brachytherapy. She had a complete loco-regional response. A supraclavicular recurrence was diagnosed three months after completing treatment and two cycles of carboplatin, docetaxel, and bevacizumab were given in April 2014. Shortly after the second cycle, she was admitted to the hospital for significant abdominal pain, diarrhea followed by symptoms of bowel subocclusion. The CT scan and endoscopic images revealed thickening of the sigmoid wall with important edema and telangiectasia. The biopsy was consistent with acute radiation-induced colitis. Because of persistent digestive symptoms, a diverting ileostomy was done few months later. The location, timing, pathology, and its association with a high-dose region are analyzed in this case report.

One-step ultrasound-based high dose rate (HDR) prostate brachytherapy with dose escalation to the dominant intra-prostatic lesion.

106 Background: To demonstrate feasibility of using high dose rate (HDR) brachytherapy to deliver 25% higher than prescription dose to the dominant intra-prostatic lesion (DIL) as defined on multi-parametric MRI for intermediate and high risk prostate cancer. Methods: Twenty six patients with predominantly unilateral disease consented to a University Ethics-approved phase II study of selective dose escalation. HDR brachytherapy was performed in weeks 1 and 3 of treatment, each delivering one fraction of 10 Gy to the whole prostate. External beam consisted of 46Gy/23 fractions starting 3 days after the first HDR fraction.T2 FSE images were obtained using 1.5T endorectal MRI in transverse, sagittal and coronal planes followed by Dynamic Contrast Enhancement after injection of gadolinium. Apparent Diffusion Coefficient maps were calculated. The DIL was contoured on the MRI and, following image registration, transposed to the preoperative TRUS performed in the treatment position. Intra-operative TRUS with sou...