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PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27.METHODS AND MATERIALS: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated.RESULTS: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed.CONCLUSIONS: The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.

PURPOSE While brachytherapy is an effective treatment for localized prostate cancer, there has been a noticeable decline in its use. Training opportunity for prostate brachytherapy has been in steady decline, with some residents receiving little to no hands-on training. This work was developed to design a training environment that uses a phantom-based simulator to teach the process of TRUS-based prostate brachytherapy METHODS AND MATERIALS A prostate phantom was fabricated from a representative prostate patient TRUS scan. Three materials were used: gelatin powder, graphite powder, and water. The prostate was developed using 9% gelatin and 0.3% graphite per 100 ml water. Five radiation oncologists were asked to qualitatively score the phantom according to image quality, haptic feedback, needle insertion quality, and its compatibility with operative tools. The contrast-to-noise ratio (CNR) was estimated using different concentrations of graphite. The elasticity of the phantom was evaluated based on ultrasound elastography measurements RESULTS The prostate phantom had an average CNR of 3.94 ± 1.09 compared to real prostate images with a CNR of 2 ± 1.8. The average Young's modulus was computed to be 58.03 ± 6.24 kPa compared to real prostate tissue (58.8 ± 8.2 kPa). Oncologists ranked the phantom as “very good” for overall quality of the phantom. They reported that needle insertion quality was “very good” during a simulated brachytherapy procedure. CONCLUSION We have developed a 3D printing prostate phantom to be used for training purposes during prostate brachytherapy. The phantom has been evaluated for image quality and elasticity. The reconstructed phantom could be used as an anthropomorphic surrogate to train residents on prostate brachytherapy procedures.

The 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).In 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 decreased0.5 standard deviation of baseline scores.Thirty-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.This novel treatment protocol incorporating MRI dose-painted HDR-BT boost and 5-fraction pelvic RT with ADT is well tolerated.

This exploratory study evaluates immunological changes in high-risk Gleason 9 prostate cancer patients treated with EBRT+BT compared to EBRT alone. Notably, BT demonstrates the potential to elicit a T cell response which may support further investigation using circulating immune cells as predictive and prognostic biomarkers for radiotherapy response.

Purpose Single-fraction HDR monotherapy for the treatment of localized prostate cancer is appealing, but published outcomes are discouraging. An approach to improve local control is MRI-guided focal dose-escalation to the dominant intraprostatic lesion (DIL). Here we report a comparison of outcomes from two phase II clinical trials with and without a focal boost. Methods Patients had low or intermediate-risk disease. Patients in Trial1 received a single 19 Gy HDR implant to the whole prostate. Trial2 incorporated an additional MRI-guided focal DIL boost to at least 23 Gy. ADT was not allowed. Toxicities (CTCAEv4.0) and quality of life (EPIC) were collected. Biochemical failure (BF) was defined as nadir +2. Univariate and multivariate logistic regression analysis was conducted to search for predictors of BF. Results Trial1 had 87 patients with a median follow-up of 62 months, while Trial2 had 60 patients with a median follow-up of 50 months. The five-year cumulative BF rate was 32.6% and 31.3%, respectively (p = 0.9). 77.5% of failures were biopsy-confirmed local failures, all of which underwent local salvage therapy. The addition of a DIL boost was not associated with worse toxicity or QOL. Baseline PSA and Gleason score correlated with BF, but none of the dosimetric parameters was a significant predictor of BF. Conclusions MRI-guided focal boost was safe and well tolerated, but did not improve local control after 19 Gy single-fraction HDR monotherapy, and the control rates were unacceptable. Single-fraction HDR monotherapy for prostate cancer should not be offered outside of clinical trials.

INTRODUCTION: We aimed to determine the minimum cross-sectional ellipsoid area on magnetic resonance (MR) of intraprostatic nodules that best predicts for subsequent targeted biopsies revealing ≥ grade group (GG) 2 disease. METHODS: Forty-six patients previously diagnosed with GG 1 prostate adenocarcinoma who received cognitively fused, MR-guided, transperineal targeted biopsies in addition to six random biopsies were included in this analysis. A Youden cutpoint analysis was used to determine the ellipsoid area in the axial plane best predicting for ≥GG 2 disease within the targeted biopsy cores and logistic regression used to assess the result. RESULTS: Median time from MR imaging to targeted biopsy was 2.4 (1.4–5.5) months. Forty of 46 (87%) patients had one nodule and 6/46 (13%) had two separate nodules on MR that received targeted biopsy. Of the 52 nodules, five (10%), 33 (63%), and 14 (27%) were Prostate Imaging-Reporting and Data System (PI-RADS) 3, 4, and 5, respectively. Thirteen (25%), six (12%), and 33 (64%) were in the anterior, medial, and posterior regions of the prostate, respectively. Median area was 0.72 (0.49–1.29) cm(2) (average diameter 9.5 mm). Fifteen of 46 (33%) patients had ≥1 random biopsy and 20/52 (38%) nodules had ≥1 targeted biopsy revealing ≥GG 2 disease. The optimal area cutpoint was ≥0.7 cm(2), with an area under the curve of 0.671 (0.510–0.832). On logistic regression, area ≥0.7 cm(2) was solely predictive of targeted biopsy revealing ≥GG 2 disease (odds ratio 6.5, 1.3–32.4, p=0.022). CONCLUSIONS: Nodule area ≥0.7 cm(2) may predict for transperineal-based targeted biopsies being positive for ≥GG 2 disease when 1–2 cores are taken.

Purpose To investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost. Material and methods Data from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan–Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups. Results A total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4–6) and delivered a median time of 2.7 months (IQR: 1.7–4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS. Conclusion Short-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT.

Background Prostate stereotactic ablative radiotherapy (SABR) regimens differ in time, dose, and fractionation. We report an update of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL), efficacy, and toxicity. Methods Men with intermediate risk prostate cancer were randomized to 40 Gy in 5 fractions delivered every other day (EOD) versus once per week (QW). Primary outcome was proportion of patients experiencing a minimally clinically important change (MCIC) in acute bowel QOL using EPIC. Secondary outcomes were toxicity, biochemical failure (BF), other QOL domains, and the rate of salvage therapy. Findings 152 men from 3 centers were randomized; the median follow-up was 62 months. Results are described for EOD versus QW. Acute bowel and urinary QOL was reported previously. Late changes in QOL were not significantly different between the two arms. There were 1 (1.3%) vs 3 (2.7%) late grade 3 + GI toxicities (p = 0.36) and 5 (6.7%) vs 2 (2.7%) late grade 3 GU toxicities (p = 0.44). Two and 5 patients had BF (5-year failure rate 3.0 vs 7.2%, p = 0.22); 0 and 4 patients received salvage therapy (p = 0.04). 5-Year OS and CSS was 95.8% and 98.6% with no difference between arms (p = 0.49, p = 0.15). 3 patients in the QW arm developed metastases. Interpretation Although we previously reported that weekly prostate SABR had better bowel and urinary QOL compared to EOD, the updated results show no difference in late toxicity, QOL, BF, or PSA kinetics. Patients should be counseled that QW SABR reduces short-term toxicity compared to QW SABR.

Purpose The current magnetic resonance imaging–computed tomography (MRI-CT) fusion-based workflow for postimplant dosimetry of low-dose-rate (LDR) prostate brachytherapy takes advantage of the superior soft tissue contrast of MRI, but still relies on CT for seed visualization and detection. Recently an MR-only workflow has been proposed that employs standard MR sequences and visualizes conventional implanted seed with positive contrast solely through MR postprocessing. In this work, the novel MR-only based workflow is compared with the clinical CT-MRI fusion approach. Methods and Materials Twenty-four prostate patients with a total of 1775 implanted LDR seeds were scanned using a 3-dimensional multiecho gradient echo sequence on a 3 Tesla MR scanner within 30 days after implantation. Quantitative susceptibility mapping was used for seed visualization. Seeds were automatically segmented and localized on the quantitative susceptibility mapping using convolutional neural network and k-means clustering, respectively. To assess the MR-only seed localization error, CT and MR-derived seed positions were coregistered, and ultimately, the resulting dose-volume histograms were compared. Results The MR-based seed visualization, segmentation, and localization generated comparable results to the CT-MR registration approach. The accuracy of the MRI-only based seed identification was 99.1%. After a rigid registration between the MR and CT-derived seed centroids, the average localization error was 0.8 ± 0.8 mm. The average prostate D90, V100, V150, and V200 for MRI-only and CT-MR fusion based dosimetry were 114.3 ± 12.5% versus 113.9 ± 11.9%, 95.1 ± 3.7% versus 95.3 ± 3.8%, 54.5 ± 14.5% versus 55.0 ± 13.2% and 22.9 ± 6.8% versus 23.2 ± 6.7%, respectively. No significant differences were observed in 3-dimensional seed positions and dosimetric parameters between MR-only and CT-MR fusion-based workflows (P > 0.2). Conclusions The MRI-only LDR postimplant dosimetry is feasible and has very good potential to eliminate the need for CT-based seed identification.

INTRODUCTION: Identifying the optimal management of unfavorable-risk (Prostate Cancer Risk Stratification [ProCaRS] high intermediate-, high-, and very high-risk categories) non-metastatic prostate cancer is an important public health concern given the large burden of this disease. We compared the rate of metastatic progression-free survival among men diagnosed with unfavorable-risk non-metastatic prostate cancer who were initially treated with radiation therapy or radical prostatectomy. METHODS: Information was obtained from medical records at two academic centers in Canada from 333 men diagnosed with unfavorable-risk non-metastatic prostate cancer between 2007 and 2012. Median followup was 90.4 months. Men were eligible for the study if they received either primary radiation therapy (n=164) or radical prostatectomy (n=169), in addition to various adjuvant and salvage therapies when deemed clinically appropriate. Patients were matched on prognostic covariates using two matching techniques. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and confidence intervals (CI) for metastatic progression-free survival between groups. RESULTS: After matching, treatment groups were balanced on prognostic variables except for percent core positivity. Hazard ratios from all Cox proportional hazards models (i.e., before and after matching, and with and without multivariable adjustment) showed no difference in the rate of metastatic progression-free survival between groups (adjusted unmatched HR 1.16, 95% CI 0.63, 2.13, p=0.64). CONCLUSIONS: Metastatic progression-free survival did not differ between men diagnosed with unfavorable risk non-metastatic prostate cancer who were treated with either radiation therapy or radical prostatectomy.

To report on long-term results of elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost for high-risk prostate cancer.This was a prospective single-arm study. Patients with high-risk disease (cT3, PSA20 ng/mL, or Gleason score 8-10) were eligible. Patients received 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous intensity-modulated radiotherapy boost of 22.5 Gy to the prostate (total dose 67.5 Gy in 25 fractions), with androgen deprivation therapy (ADT) for 2-3 years. The primary endpoint was biochemical failure. Secondary endpoints included distant metastases and overall survival. Multivariable analysis was performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0.230 patients enrolled. Median follow-up was 11.2 years (IQR 8.1-12.9). At 10 years, cumulative incidence of biochemical failure was 33.4%, distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir ≥0.05 ng/mL was associated with biochemical failure (HR 6.8, 95% CI 4-11.8, p 0.001) and distant metastases (HR 7.5, 95% CI 3.9-14.5, p 0.0001). PSA nadir ≥0.1 ng/mL (HR 5.2, 95% 2.2-12, p = 0.0001) and ADT use ≤12 months (versus24 months) (HR 2.3, 95% CI 1.3-3.9, p = 0.004) were associated with worse survival. The 5-year cumulative incidence of any late grade ≥3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively.EPNI and a simultaneous hypofractionated prostate boost combined with long-term ADT for high-risk prostate cancer resulted in acceptable 10-year biochemical control and survival with low grade ≥3 toxicity.

Purpose Stereotactic ablative radiotherapy (SABR) is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index and lead to a better quality of life (QOL). Here we report the outcomes of a QOL comparison between two phase II clinical trials: two vs. five fraction prostate SABR. Methods Patients had low or intermediate risk PCa. The doses prescribed were 26 Gy/2 and 40 Gy/5. Expanded prostate cancer index composite was collected. Urinary, bowel and sexual domains were analyzed. Minimal clinically important change (MCIC) was defined as >0.5 standard deviation. Results 30 and 152 patients were treated with 2-fraction and 5-fraction SABR. Median follow-up was 55 and 62 months. Five-year biochemical failure rate was 3.3% and 4.6%. The 2-fraction cohort had a significantly better mean QOL over time in the bowel domain ( p = 0.0004), without a significant difference in the urinary or sexual domains. The 2-fraction cohort had a significantly lower rate of bowel MCIC (17.8% vs 42.3%, p = 0.01), but there was no difference in urinary (24.1% vs 35.7%) or sexual (15.3% vs 29.2%) MCIC. For MCIC x2 (moderate QOL change), the 2-fraction trial had significantly lower MCIC rates in both the bowel (7.1% vs 24%, p = 0.04) and sexual (0 vs 17.6%, p = 0.01) domains. Conclusions 2-Fraction SABR is feasible to deliver and well tolerated, with significant signals of improved bowel and sexual QOL. A randomized trial of two vs. five fractions for prostate SABR is needed to confirm the promising findings of this study.

To report the 5-year outcomes from a single institution, prospective, phase 1/2 study on hypofractionated, accelerated radiation therapy to the prostate bed after radical prostatectomy.Patients enrolled in this study were all eligible for postoperative radiation therapy and received a prescribed dose of 51 Gy in 17 fractions to the prostate bed. On follow-up, gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0; prostate-specific antigen (PSA) was evaluated and quality of life was assessed using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire.A total of 30 patients were enrolled between 2008 and 2011. Median age was 65 (52-75) years. Median pretreatment PSA was 0.12 ng/mL (0.01-1.42). Twenty-six (93%) patients had Gleason ≤7 disease, 13 (43%) had pT3 disease, and 20 (67%) had positive margins. Twenty-six patients (87%) underwent radiation therapy as salvage treatment. After a median follow-up of 6.4 (2.1-8.1) years, no patient experienced Common Terminology Criteria for Adverse Events grade 3/4 toxicity. Eleven patients (37%) had grade 2 genitourinary and 2 (7%) had grade 2 gastrointestinal toxicity. At baseline and 5 years after radiation therapy, mean EPIC urinary domain score was 80% (standard deviation, 18%) and 82% (17%). Mean EPIC bowel domain score was 93% (13%) and 93% (15%). One patient (4%) had a minimally clinically important change in urinary domain score and 1 patient (4%) had a minimally clinically important change in bowel domain score. Nelson-Aalen estimated cumulative incidence of biochemical failure was 31% (nadir +0.2) and 18% (nadir +2.0) at 5 years. Four-year PSA ≥0.4 was predictive of subsequent androgen deprivation therapy use (Nelson-Aalen cumulative incidence: 1.45; P .0001). Five patients (17%) received hormonal therapy for biochemical failure. Nelson-Aalen estimated cumulative incidence of hormone therapy use was 14% at 5 years. All patients who received hormone therapy had PSA0.4 at 4 years.In this phase 1/2 study, hypofractionated postoperative radiation therapy seems to have good clinical efficacy without significant late toxicity. Phase 3 studies are warranted.

Purpose Ultrahypofractionation is appealing for prostate cancer (PCa) due to low α/β, and increasing the dose per fraction could improve the therapeutic index. Here we report the outcomes of a phase II prostate SABR trial using two fractions. Methods Patients had low or intermediate risk prostate cancer. Three gold fiducials were implanted for image guidance. The clinical target volume (CTV) included the prostate only, and the planning target volume (PTV) was a 3 mm expansion enabled through the use of a rectal immobilization device. The dose prescribed was 26 Gy in 2 weekly fractions (EQD2 110 Gy1.4). The primary endpoint was quality of life using EPIC, and minimal clinically important change (MCIC) was defined as an EPIC QOL decrease >0.5 SD. Results 30 patients were accrued with a median follow-up of 49.3 months. 10% had low-risk, 33% had favourable intermediate-risk and 57% had unfavourable intermediate-risk PCa. Five patients received a short course of ADT. Median nPSA was 0.2 ng/ml. One patient had BF and is being observed. 56.6% of patients had a 4yPSARR. Six (20.7%) patients had a MCIC in the urinary domain, 6 (21.4%) had a MCIC in the bowel domain, and 3 (20%) had a MCIC in the sexual domain. Conclusions Two-fraction SABR in prostate cancer is safe and feasible, with a minimal change in QOL and a low rate of late grade 3–4 toxicity. The PSA kinetics and biochemical control rates are encouraging given that the majority had unfavourable intermediate-risk disease, although longer follow-up is required.

To summarize the clinical outcomes of stereotactic body radiotherapy (SBRT) for metastatic breast cancer (mBC) from a large institution.Patients with mBC who received extra-cranial SBRT to metastatic lesions from 2011 to 2017 were identified. Treatment indications were: oligometastases, oligoprogression, and local control of dominant tumor (CDT). Endpoints included overall survival (OS), progression-free survival (PFS), local control (LC) and cumulative incidence of starting/changing chemo or hormonal therapy (SCT). Univariate and multivariate analyses were used to identify predictive factors.We analyzed 120 patients (193 treated metastatic lesions) with a median follow up of 15.25 months. 1-and 2-year LC rates were 89% and 86.6%, respectively. 1-and 2-year OS rates were 83.5% and 70%, respectively, with treatment indication and molecular subtype being the predictive factors on MVA. 1-year OS was 91.0%, 78.5% and 63.9% for oligometastases, oligoprogression and CDT, respectively (p = 0.003). The worst OS was seen in basal subtype with 1-and 2-year OS rates of 59.2% and 39.5% (p = 0.01). Treatment indication was found to be predictive for PFS and lower rates of SCT on MVA. 1-and 2-year PFS rates were 45% and 32%, respectively. The 1-year PFS for oligometastases, oligoprogression, and CDT was 66%, 19.6%, and 14.3%, respectively (p 0.001). The cumulative incidence of SCT at 1-year was 12% for oligometastases, 39.7% for oligoprogression and 53.3% for CDT (p 0.001).Patients treated for oligometastases have better OS and PFS than those treated for oligoprogression or CDT. SBRT may delay SCT in mBC patients, particularly those with oligometastases. SBRT provided an excellent LC in mBC patients.

Introduction Despite treatment advances, the prognosis of locally advanced pancreatic cancer is poor. Treatment remains varied and includes systemic and radiotherapy (RT). Stereotactic body radiotherapy (SBRT), highly conformal high-dose RT per fraction, is an emerging treatment option. Materials and methods We performed a single-institution retrospective review of patients with pancreatic adenocarcinoma treated with SBRT from 2015-2017. The median dose was 27 Gy (range: 21-36 Gy) in three fractions. Endpoints included local progression (RECIST 1.1; Response Evaluation Criteria in Solid Tumors 1.1), distant metastasis, overall survival, and toxicity. Results Forty-one patients were treated, with a median follow-up of eight months. Patients who received SBRT had unresectable (49%), metastatic (17%), or borderline resectable (7%) disease, declined surgery (17%), medically inoperable (7%), or developed local recurrence following the Whipple procedure (2%). The six-month and one-year rates of local progression-free survival, distant metastasis-free survival, and overall survival were 62% and 55%, 44% and 32%, and 70% and 49%, respectively. Five patients (12%) experienced seven late gastrointestinal (GI) grade 3 events. Conclusion SBRT may be considered a treatment option to achieve local control of pancreatic cancer and is associated with a modest risk of severe late GI toxicities. Systemic therapies remain important, given the proportion of patients who develop distant metastases.

Liver metastases are common in patients with neuroendocrine tumours. For patients, management must balance disease control with consideration of toxicity, given limited treatment options. Everolimus has demonstrated effectiveness in neuroendocrine neoplasms. Given emerging data of a synergistic effect with radiation therapy, we evaluated combined everolimus and radiation for neuroendocrine liver metastases. This single-arm, single-centre prospective pilot study evaluated the safety and efficacy of combined everolimus and radiotherapy for well-differentiated neuroendocrine liver metastases. Patients with unresectable liver metastases received everolimus for 30 days, followed by concurrent everolimus and liver radiotherapy, then a further 14 days of everolimus. Tolerability was evaluated using the CTCAE v.4.03. Individual metastasis response rate and local control were measured by RECIST v1.1. Overall survival, progression-free survival and freedom from a change in systemic therapy were estimated by the Kaplan–Meier method. Forty metastases were treated in 14 patients. No grade 3 or higher toxicities were identified in the concurrent treatment phase; one patient developed grade 3 toxicity in the post-radiation phase. Overall response rate was 38%. One- and 2-year local control were 97% and 71%. Median progression-free survival was 12 months. One- and 2-year overall survival were 100% and 92%. In conclusion, combined everolimus and radiation are well-tolerated for neuroendocrine liver metastases and are associated with excellent local control. The approach of selective local ablation of oligometastatic or oligoprogressive disease warrants further evaluation in this patient population.

Purpose Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy treatment planning remains a significant challenge. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study assesses the dosimetric impact attributed to differences in DIL contours generated using commonly available MRI to TRUS automated registration: rigid, semi-rigid, and deformable image registration, respectively. Methods and Materials Ten patients, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists with expertise in TRUS-based high-dose-rate brachytherapy were asked cognitively to transfer the DIL from the mpMRI images of each patient to the TRUS image. The contours were analyzed for concordance using simultaneous truth and performance level estimation (STAPLE) algorithm. The impact of DIL contour differences due to registration variability was evaluated by comparing the STAPLE-DIL dosimetry from the reference (STAPLE) plan with that from the evaluation plans (manual and automated registration) for each patient. The dosimetric impact of the automatic registration approach was also validated using a margin expansion that normalizes the volume of the autoregistered DILs to the volumes of the STAPLE-DILs. Dose metrics including D90, Dmean, V150, and V200 to the prostate and DIL were reported. For urethra and rectum, D10 and V80 were reported. Results Significant differences in DIL coverage between reference and evaluation plans were found regardless of the algorithm methodology. No statistical difference was reported in STAPLE-DIL dosimetry when manual registration was used. A margin of 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm was required to be added for rigid, semi-rigid, and deformable registration, respectively, to mitigate the difference in STAPLE-DIL coverage between the evaluation and reference plans. Conclusion The dosimetric impact of integrating an MRI-delineated DIL into a TRUS-based brachytherapy workflow has been validated in this study. The results show that rigid, semi-rigid, and deformable registration algorithms lead to a significant undercoverage of the DIL D90 and Dmean. A margin of at least 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm is required to be added to the rigid, semi-rigid, and deformable DIL registration to be suitable for DIL-boosting during prostate brachytherapy.

Background: Approved almost 15 years ago for use in the chemotherapy setting, palonosetron, a 2nd generation 5-hydroxtryptamine 3 receptor antagonist (5-HT3 RA), has demonstrated efficacy in preventing chemotherapy-induced nausea and vomiting. However, its utility in the prophylaxis and treatment of radiation-induced nausea and vomiting (RINV) has yet to be evaluated. In this pilot study, we investigated the rates of control in RINV in patients with pre-existing emesis. Methods: Patients with pre-existing emesis undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2–10 after treatment). Prophylaxis and rescue (PR) was defined as a decrease in anti-emetic use, or episodes of nausea and/or vomiting from baseline. Complete prophylaxis (CP) was defined as no increase in anti-emetic use, or episodes of nausea and/or vomiting. Secondary endpoints included control of nausea and quality of life (QOL), as assessed with the Functional Living Index—Emesis and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire—Core 15 Palliative. Results: Fourteen patients were enrolled. Rates of control were higher in the acute phase (n=14) for nausea (PR =42.9%, CP =42.9%) and vomiting (PR =21.4%, CP =71.4%) compared to the delayed phase (n=13) for nausea (PR =42.9%, CP =7.7%) and vomiting (PR =15.4%, CP =53.8%). Conclusions: Palonosetron appears to be safe and patients with pre-existing emesis receiving palliative radiotherapy. More studies are needed to investigate its efficacy in this patient population.

Prostate stereotactic body radiotherapy (SBRT) regimens differ in time, dose, and fractionation. We completed a multicentre, randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL).Men with low and intermediate-risk prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered once per week (QW) vs. every other day (EOD). QOL was assessed using the Expanded Prostate Cancer Index Composite. The primary endpoint was the proportion with a minimum clinically important change (MCIC) in bowel QOL during the acute (≤12 week) period, and analysis was by intention-to-treat. ClinicalTrials.gov NCT01423474.152 men from 3 centres were randomized with median follow-up of 47 months. Patients treated QW had superior acute bowel QOL with 47/69 (68%) reporting a MCIC compared to 63/70 (90%) treated EOD (p = 0.002). Fewer patients treated QW reported moderate-severe problems with bowel QOL during the acute period compared with EOD (14/70 [20%] vs. 40/70 [57%], p 0.001). Acute urinary QOL was also better in the QW arm, with 52/67 (78%) vs 65/69 (94%) experiencing a MCIC (p = 0.006). There were no significant differences in late urinary or bowel QOL at 2 years or last follow-up.Prostate SBRT delivered QW improved acute bowel and urinary QOL compared to EOD. Patients should be counselled regarding the potential for reduced short-term toxicity and improved QOL with QW prostate SBRT.

Background: Palonosetron is an effective antiemetic in chemotherapy-induced nausea and vomiting (CINV), but has yet to be studied in the radiation setting. The purpose of the present study was to investigate the efficacy and safety of palonosetron in the prophylaxis of radiation-induced nausea and vomiting (RINV). Methods: Patients without existing nausea and vomiting undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg orally before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2–10 after treatment). The primary endpoint was control of vomiting. Complete control was defined as no use of rescue medication and no episodes of nausea or vomiting. Secondary endpoints included control of nausea and quality of life (QOL). QOL was assessed with the Functional Living Index—Emesis and the European Organisation for Research and Treatment of Cancer QOL Questionnaire—Core 15 Palliative (C15-PAL). Results: In all evaluable patients (n=75), complete control of vomiting was 93.3% in the acute phase and 93.2% in the delayed phase. Complete control of nausea was 74.7% in the acute phase and 74.0% in the delayed phase. Conclusions: Results suggest improved control in RINV compared to historical reports with first generation serotonin receptor antagonists (RA). A randomized study will be needed to confirm this finding.

Background: Patients with advanced cancer often experience a multitude of symptoms. Due to the potential interrelation of symptoms, symptom clusters of 2 or more concurrent symptoms have been advocated for use in the palliative setting to provide better management of symptoms. Methods: The principal component analysis (PCA), exploratory factor analysis (EFA) and hierarchal cluster analysis (HCA) were conducted on responses to items 1–14 in the European Organisation for Research and Treatment of Cancer Quality of Life-C15-Palliative (EORTC QLQ-C15-PAL) at baseline and days 5 and 10 following RT. Results: There was complete data for 109, 90 and 87 patients at baseline, day 5 and day 10 respectively. The average age was 72 years. The most common site of primary was the prostate (36.7%), and almost all patients presented with bone metastases (95.4%). Analyses identified 2–4 clusters at each interval. From baseline to day 10 follow-up, across all analyses, items associated with physical functioning clustered consistently with shortness of breath. Pain and pain interference clustered with nausea at baseline; and with sleep at both follow-up intervals. Cronbach’s alpha values for the clusters ranged from 0.53 to 0.90. Conclusions: Fluctuation of symptom clusters was observed in a short time frame following palliative RT. Although clusters were dynamic, several items tended to cluster together. Further research is required to validate these clusters.

Background and purpose: Antiemetic guidelines suggest daily prophylaxis with a serotonin3 receptor antagonist (5-HT3RA) as an option for patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal cancer, despite the risks that 5-HT3RA-induced constipation may pose. We explored the incidence of patient-reported vomiting, retching, nausea and antiemetic intake among patients in this setting to determine if these risks are justified. Materials and methods: We carried out a single-centre non-randomised prospective cohort study of adult patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal adenocarcinoma. Patients recorded symptoms and medication intake daily until 7 days following treatment completion. Results: From 33 evaluable patients, we collected 1407 days of patient-reported data. Vomiting was reported by 7 patients (21%), retching by 5(15%) and nausea by 21(64%). No patients were administered prophylactic antiemetics. The median number of days with vomiting was 2, and the cumulative number of days for all affected patients was 22 (1.6% of 1407 evaluable days). There were no differences in PTV or small bowel loop V15Gy, V45Gy and V50Gy volumes between patients that did and did not vomit. Conclusions: The cumulative incidence of days with vomiting was only 1.6%. 5-HT3RA prophylaxis during long-course neoadjuvant treatment seems unnecessary. Keywords: Antiemetic, Nausea, Patient-reported outcome, Radiation therapy, Rectal cancer, Vomiting

Purpose This work presents the application of a machine learning (ML) algorithm to automatically generate high-quality, prostate low-dose-rate (LDR) brachytherapy treatment plans. The ML algorithm can mimic characteristics of preoperative treatment plans deemed clinically acceptable by brachytherapists. The planning efficiency, dosimetry, and quality (as assessed by experts) of preoperative plans generated with an ML planning approach was retrospectively evaluated in this study. Methods and Materials Preimplantation and postimplantation treatment plans were extracted from 100 high-quality LDR treatments and stored within a training database. The ML training algorithm matches similar features from a new LDR case to those within the training database to rapidly obtain an initial seed distribution; plans were then further fine-tuned using stochastic optimization. Preimplantation treatment plans generated by the ML algorithm were compared with brachytherapist (BT) treatment plans in terms of planning time (Wilcoxon rank sum, α = 0.05) and dosimetry (1-way analysis of variance, α = 0.05). Qualitative preimplantation plan quality was evaluated by expert LDR radiation oncologists using a Likert scale questionnaire. Results The average planning time for the ML approach was 0.84 ± 0.57 minutes, compared with 17.88 ± 8.76 minutes for the expert planner ( P =.020). Preimplantation plans were dosimetrically equivalent to the BT plans; the average prostate V150% was 4% lower for ML plans ( P =.002), although the difference was not clinically significant. Respondents ranked the ML-generated plans as equivalent to expert BT treatment plans in terms of target coverage, normal tissue avoidance, implant confidence, and the need for plan modifications. Respondents had difficulty differentiating between plans generated by a human or those generated by the ML algorithm. Conclusions Prostate LDR preimplantation treatment plans that have equivalent quality to plans created by brachytherapists can be rapidly generated using ML. The adoption of ML in the brachytherapy workflow is expected to improve LDR treatment plan uniformity while reducing planning time and resources.

Purpose There is growing concern that single-fraction HDR monotherapy to a dose of 19 Gy is suboptimal for the treatment of localized prostate cancer. We report the results of a phase II prospective trial of single-fraction 19 Gy HDR monotherapy with MRI-guided simultaneous focal boost. Methods Eligible patients had low or intermediate risk prostate cancer and an identified lesion on MRI. TRUS based single-fraction HDR monotherapy with MRI fusion was delivered. The dose prescribed was 19 Gy to the prostate and ≥23 Gy to the dominant intraprostatic lesion (DIL). ADT was not used. The purpose is to report early efficacy results. Results 60 patients were enrolled, with a median follow-up of 39 months. With MRI T-stage incorporated into the risk-group criteria, 8% had low-risk, 35% had favorable intermediate-risk and 57% had unfavorable intermediate-risk disease. The median dose to 90% of the DIL (D90) was 27.2 Gy, and the median prostate V100% was 96.9%. No acute or late grade ≥3 bowel or urinary toxicity was observed. The cumulative BF probability was 15.2% at 36 months and 31.6% at 48 months. All patients that were fully investigated had local failure only, and 88% of the local failures were at the site of original DIL. The median PSA nadir was 0.79 ng/ml, with a median time to nadir of 32 months. Conclusions Focal boost to the MRI-specified gross tumor was well tolerated, but did not adequately improve local control. Single-fraction HDR monotherapy to 19 Gy for prostate cancer provides suboptimal local control, and should not be offered outside of clinical trials.

Purpose: Radio-recurrent prostate cancer is typically detected by a rising prostate-specific antigen and may reflect local or distant disease. Positron emission tomography (PET) radiotracers targeting prostate-specific membrane antigen, such as 18F-DCFPyL have shown promise in restaging men with recurrent disease postprostatectomy but are less well characterized in the setting of radio-recurrent disease. Methods and Materials: A prospective, multi-institutional study was conducted to evaluate the effect of 18F-DCFPyL PET/computed tomography (CT) when added to diagnostic imaging (DI; CT abdomen and pelvis, bone scan, multiparametric magnetic resonance imaging pelvis) for men with radio-recurrent prostate cancer. All men were imaged with DI and subsequently underwent 18F-DCFPyL PET/CT with local and central reads. Tie break reads were performed as required. Management questionnaires were completed after DI and again after 18F-DCFPyL PET/CT. Discordance in patterns of disease detected with 18F-DCFPyL PET/CT versus DI and changes in management were characterized. Results: Seventy-nine men completed the study. Most men had T1 disease (62%) and Gleason score

Purpose/objective To report biochemical control associated with single fraction 15 Gy high-dose-rate brachytherapy (HDR-BT) boost followed by external beam radiation (EBRT) in patients with intermediate-risk prostate cancer. Materials and methods A retrospective chart review of all patients with intermediate-risk disease treated with a real-time ultrasound-based 15 Gy HDR-BT boost followed by EBRT between 2009 and 2016 at a single quaternary cancer center was performed. Freedom from biochemical failure (FFBF), cumulative incidence of androgen deprivation therapy use for biochemical or clinical failure post-treatment (CI of ADT) and metastasis-free survival (MFS) outcomes were measured. Results 518 patients met the inclusion criteria for this study. Median age at HDR-BT was 67 years (IQR 61–72). 506 (98%) had complete pathologic information available. Of these, 146 (28%) had favorable (FIR) and 360 (69%) had unfavorable (UIR) intermediate-risk disease. 83 (16%) received short course hormones with EBRT + HDR. Median overall follow-up was 5.2 years. FFBF was 91 (88–94)% at 5 years. Five-year FFBF was 94 (89–99)% and 89 (85–94)% in FIR and UIR patients, respectively (p = 0.045). CI of ADT was 4 (2–6)% at 5 years. Five-year CI of ADT was 1 (0–3)% and 5 (2–8)% in FIR and UIR patients, respectively (p = 0.085). MFS was 97 (95–98)% at 5 years. Five-year MFS was 100 (N/A-100)% and 95 (92–98)% in FIR and UIR patients, respectively (p = 0.020). Conclusion In this large cohort of intermediate-risk prostate cancer patients, 15 Gy HDR-BT boost plus EBRT results in durable biochemical control and low rates of ADT use for biochemical failure.

High-dose-rate brachytherapy boost plus external beam radiation therapy is an established option for intermediate-risk prostate cancer (PCa). Stereotactic body radiation therapy (SBRT) boost can potentially mimic high-dose-rate boost and could be a viable alternative. Here we report the long-term outcomes of a phase 1 dose-escalation trial of single-fraction SBRT boost.Patients had intermediate-risk PCa and were accrued to 3 different SBRT single-fraction dose-level cohorts (10 Gy, 12.5 Gy, and 15 Gy). All received supplemental radiation therapy afterwards (37.5 Gy in 15 fractions). Three gold fiducials were implanted for image guidance. Patients were simulated and treated with a foley catheter and intrarectal balloon. A T2 magnetic resonance imaging scan was used for contouring, and a cine magnetic resonance imaging scan was used to calculate patient-specific internal target volume margins. Toxicity and quality-of-life data were collected using Common Terminology Criteria for Adverse Events v3.0 and the Expanded Prostate Cancer Index Composite.30 patients were accrued, 10 in each cohort. Median follow-up was 72 months. 60% had unfavorable intermediate-risk PCa. Two patients in the 15 Gy cohort developed late grade ≥3 gastrointestinal and genitourinary toxicity, with 1 patient suffering from a grade-4 rectal fistula after a rectal ulcer was biopsied repeatedly. Two patients had biochemical failure. Median PSA nadir was 0.4 ng/mL with 10 Gy, 0.09 ng/mL with 12.5 Gy and 0.07 ng/mL with 15 Gy. Median PSA at 4 years as well as proportion achieving a nadir0.2 ng/mL improved significantly with higher doses. There was no significant change in quality of life from baseline in any of the domains, and the minimal clinically important change was not statistically different between the 3 cohorts.Other than a grade 4 toxicity, which may in part be due to repeated biopsies of a rectal ulcer, single-fraction SBRT boost was feasible and well tolerated. Larger studies are warranted to better document the outcomes of such an approach.

Introduction: Stereotactic body radiation therapy allows for the precise delivery of high-dose radiation to disease sites and is becoming increasingly used to treat nonspine bone metastases. Previous studies have shown that remineralization of lytic bone metastases follows after conventional radiotherapy. The objective of this study was to investigate changes in bone density in nonspine bone metastases following stereotactic body radiation therapy. Methods: A retrospective review was conducted for all patients treated with stereotactic body radiation therapy to nonspine bone metastases between May 2011 and April 2014. A minimum of 1 pretreatment and 1 posttreatment computed tomography scan was required. An independent musculoskeletal radiologist contoured the lesions on the most representative computed tomography slices. Density was measured in Hounsfield units and analyzed using pretreatment and posttreatment ratios. Results: Forty sites were treated (55% lytic, 30% sclerotic, and 15% mixed). The median follow-up duration was 7 months. Lytic osseous metastases from renal cell carcinoma progressed during initial follow-up imaging and then returned to baseline. Of 9 lytic lesions not from renal cell carcinoma, 6 showed an immediate increase in density and 2 remained stable. Six of 7 sclerotic lesions from prostate cancer showed decreased density throughout all follow-ups. Conclusion: Stereotactic body radiation therapy is efficacious in the remineralization of lytic and demineralization of sclerotic nonspine bone metastases.

Insufficiency fractures are stress fractures that occur from normal weight-bearing on weakened bone. Radiation treatment to malignancies in the prostate, rectum, anus, or cervix may increase the risk of insufficiency fractures in the pelvic region by damaging osteoblasts that are essential to bone formation. In elderly women with cancer, this risk is greater due to their susceptibility to developing osteoporosis. These fractures may be confused with pathological fractures resulting from bone metastases on imaging and should be identified for proper management. We report two cases in which two women developed painful insufficiency fractures in the pelvic region after receiving radiation treatment to the rectum. After consulting an orthopedic surgeon, one patient underwent a cementoplasty, while the other patient was encouraged to take bone strengthening medications.

Background: In recent years, stereotactic body radiation therapy (SBRT) has become increasingly used for the management of non-spine bone metastases. Few studies have examined the radiological changes in bone metastases after treatment with SBRT and there is no consensus about what constitutes radiologic response to therapy. This article describes various changes on CT after SBRT to non-spine bone metastases in eight selected cases. Methods: A retrospective review was conducted for patients treated with SBRT to non-spine bone metastases between November 2011 and April 2014 at Sunnybrook Health Sciences Centre. A musculoskeletal radiologist identified eight illustrative cases of interest and provided a description of the findings. Results: Different radiological changes following SBRT were described, including: remineralization of lytic bone metastases, demineralization of sclerotic bone metastases, pathologic fracture, size progression and response in different lesions, as well as lung fibrosis after SBRT to a rib metastasis. Conclusions: We reviewed the radiological images of eight selected cases after SBRT to nonspine bone metastases and a number of characteristic findings were highlighted. We recommend future studies to correlate radiologic changes with clinical outcomes including pain relief, toxicity and long-term local control.

We conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time-dose-fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored.The study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis.In total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26-0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04-0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09-0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08-1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28-11.07) with BFFS.The incidence of PSA bounce was independent of time-dose-fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.

Purpose This article describes how a targeted application of Lean methodology in a high-volume brachytherapy department can result in significant and sustained change that benefits patients and staff. Methods and Materials In November 2013, staff and physicians carried out a 3-day Kaizen (rapid improvement) Event with three identified goals: to reduce same-day patient wait times, to reduce staff-hours spent scheduling patients, and to increase the utilization of the brachytherapy operating room (OR). Results At the Lean Event, staff drew up a future state that included a standard booking process (standard booking times for procedures, a booking guideline, and OR schedule reviews) and shortly after the event, time checks, or procedure checkpoints, were introduced to make teams aware of how each case proceeds through key milestones. The implementation of these changes led to a reduction in the average same-day wait times for patients by 37 minutes and 2 seconds and eliminated the need for a team of seven to eight staff to meet weekly to create a feasible OR schedule. Instead, a team of two to three reviews the schedule with the goal of optimizing the utilization of the OR on anesthesia-staffed days and, as a result, OR utilization has gone from 59% to 97%. Conclusions By using Lean methodology and by emphasizing the Lean concepts of measurement, standardization, simplification, and staff participation, the Brachytherapy Leadership team was able to address barriers to change and improve the department's quality metrics. If an institution has to choose between starting on a small-scale project with Lean or not at all, organizations are encouraged to start with a targeted application of Lean and then expand by conducting research on quality and/or striking a quality improvement committee.

Purpose Five-fraction stereotactic ablative radiation therapy appears to be gaining popularity in treatment of prostate cancer, but it has not been extensively tested in the context of pelvic radiation. The objective of this prospective prostate and pelvic SABR study is to report the acute toxicity, late toxicity, and quality of life (QoL) after study completion. Methods and Materials A phase 1/2 study was conducted for patients with high-risk prostate cancer. Radiation therapy was planned to deliver 25 Gy to pelvis and seminal vesicles (SV) and a simultaneous integrated boost (SIB) of up to 40 Gy to the prostate in 5 fractions, weekly, over 29 days. Androgen deprivation therapy was used for 12 to 18 months. Common Terminology Criteria for Adverse Events version 3.0 was used to assess worst acute and late toxicities. QoL data was captured using the Expanded Prostate Cancer Index Composite questionnaire (EPIC). Results Thirty patients completed the planned treatment with a median follow-up of 25.7 months (range, 18.5-30.7 months). The following “worst” acute and late toxicities were observed: grade 2 genitourinary toxicity, 46.7% and 52%, respectively; grade 2 gastrointestinal toxicity, 3.3% and 32%, respectively. No grade 3 or higher toxicities were noted. Mean (95% confidence interval) EPIC urinary QoL scores were 86.6 (81.9-91.3), 87.1 (81.4-92.6), and 87.9 (80.1-95.7) at baseline, 3 months and 24 months; bowel scores were 94.1 (91.3-97.0), 93.2 (89.1-97.2), and 92.4 (87.7- 97.1), respectively. Conclusions This gantry-based novel fractionation schedule incorporating pelvic radiation for high-risk prostate cancer in combination with androgen deprivation therapy is feasible and well tolerated.

PURPOSE This study investigates the inter-observer variability of contouring non-spine bone metastases using the planning CT alone vs. the addition of MRI T1 and T2 imaging sequences. METHODS AND MATERIALS 10 cases of non-spine bone metastases treated with SBRT at our institution were selected. The gross tumor volume (GTV) for each case was delineated by six SBRT radiation oncologists (RO) and one diagnostic radiologist (DR) on the treatment planning CT. After a minimum of three months, each case was re-contoured on the CT fused with a MRI T1 sequence followed by a MRI T2 sequence. STAPLE consensus contours were created from the RO volumes and inter-observer variability was measured using both κ agreement and the Dice coefficient (DSC). RESULTS In total, 180 RO contours were analyzed within three datasets (CT, CT + MRI T1 and CT + MRI T1 + MRI T2). The mean GTV was 16.95 cm3 (range, 0.12-269.6 cm3). The RO κ agreement was 0.6129 based on CT alone, and significantly increased to 0.7045 in the CT + MRI T1 (P = .042) dataset and 0.7017 in the CT + MRI T1 + MRI T2 dataset (P = .048). The mean DSC in the CT alone dataset was 0.7047, and significantly increased to 0.7628 in the CT + MRI T1 dataset (P < .001) and 0.7544 in the CT + MRI T1 + MRI T2 dataset (P = .001). There were no statistical differences in RO κ agreement (P = .948) or mean DSC (P = .573) when comparing the CT + MRI T1 and CT + MRI T1 + MRI T2 datasets. The DSC agreement between DR and RO volumes was lowest (0.6887) in the CT alone dataset and significantly increased to 0.7398 in the CT + MRI T1 dataset (P = .003) and 0.7342 in the CT + MRI T1 + MRI T2 dataset (P = .008). CONCLUSIONS The fusion of MRI T1 images to CT significantly reduced inter-observer variability amongst RO's in delineating non-spine bone metastases, and improved agreement between GTVs delineated by the RO to the DR.

Aims To present the initial findings of a single institution, phase I/II study investigating hypofractionated radiotherapy in patients undergoing post-prostatectomy treatment. Materials and methods Patients requiring postoperative radiotherapy were prospectively enrolled. Dose was prescribed to the prostate bed with 51 Gy in 17 daily fractions. Androgen deprivation was optional. Acute and late gastrointestinal/genitourinary toxicity were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 and quality of life was assessed using the Expanded Prostate Cancer Index Composite evaluation tool. Prostate-specific antigen (PSA) was evaluated at every follow-up. Results Thirty patients were enrolled between 2009 and 2011. The median age was 65 years and most had Gleason 7 disease (86%) with pT2c or pT3a (82%). Positive margins were documented in 67% of the patients. The median pre-treatment PSA was 0.12 ng/ml. The median follow-up was 24 months. Overall toxicity was low, with >80% of patients having ≤ grade 1 acute toxicity in both genitourinary and gastrointestinal realms. Similarly, only two patients (6%) experienced grade 2/3 late gastrointestinal/genitourinary toxicity. Quality of life scores were also indicative of a well-tolerated treatment. PSA failure was seen in five patients (17%). Conclusions We present a hypofractionated schedule of postoperative prostate radiotherapy that is both well tolerated in terms of both toxicity and quality of life measures. Initial PSA control is encouraging. Further evaluation with a longer follow-up and a larger cohort is warranted.

Background: Pelvic radiation may cause radiation enteritis, which commonly manifests as diarrhea. Radiation to the abdomen or pelvis may also cause radiation-induced nausea and vomiting (RINV) which is often treated with anti-emetics such as serotonin (5-HT3) receptor antagonists (RA). However, a common side effect of these anti-emetic medications is constipation. Both diarrhea and constipation can have a significant impact on patient quality of life (QOL). The objective of this study was to assess the prevalence of diarrhea and constipation in patients receiving pelvic radiation and anti-emetics. Methods: Patients undergoing pelvic radiation between January 2011 and March 2017 at Sunnybrook Odette Cancer Centre were enrolled in three prospective clinical trials studying the efficacy of various anti-emetics for RINV prophylaxis. Patients completed QOL questionnaires which included a single question about severity of constipation at baseline, day 5 and 10 during radiation if applicable, and day 5 and 10 after completion of radiation; severity was measured on a 4-point Likert scale ranging from 1= “not at all” to 4= “very much”. Patients also recorded severity of diarrhea throughout baseline, treatment, and 10 days follow-up via daily diaries; responses were qualitative ranging from “no diarrhea” to “severe diarrhea” on a 4-point scale. Results: Fifty-nine patients received pelvic radiation across the three trials. The average constipation score at baseline was 1.69 [standard deviation (SD) 0.93], and increased up to 2.33 (SD 1.03) at day 10 during treatment. Following treatment, the average score decreased to 1.61 (SD 0.80) at day 10 follow-up with the majority of patients reporting no constipation at this time (57.7%). The average diarrhea score at baseline was 1.03 (SD 0.18) and remained stable throughout treatment and follow-up. A vast majority of patients reported no diarrhea after day 10 follow-up (96.4%). Conclusions: Constipation was more prevalent than diarrhea during radiation treatment and up to day 10 after radiation to the pelvis. Approximately 42% of patients will have constipation on day 10 post radiation. Further research is needed to assess the causes of constipation including analgesics, and the effect on QOL during and shortly after palliative radiation to the pelvis.

There are numerous standard treatment options for men diagnosed with localized prostate cancer. Multidisciplinary consultation before decision-making is a consensus- and quality-based objective in Ontario. With the goals of working together more collaboratively and to provide higher quality information for patients at the time of decision-making, a prostate cancer community partnership consensus (PCPC) panel was formed among six partnering centers in the Greater Toronto Area.Five iterative meetings were held among 40 prostate cancer specialists (32 urologists and 8 radiation oncologists) who participate in multidisciplinary clinics. The meetings defined the goals of the partnership as well as the topics and questions the group would address together. Answers to these questions were developed by formal consensus:= 75% of participants had to agree with wording based on secret ballots to achieve consensus.All six groups wanted to participate to improve patient care/decision-making. Forty-one questions addressing 30 issues were derived from the literature and the group's collective experience. These issues were cross-tabbed against five management options: active surveillance, radical prostatectomy, low dose rate brachytherapy, high dose rate brachytherapy boost and external beam radiation. Answers common to all modalities were coalesced. Eighty-six issues were subjected to formal consensus. After three rounds of secret ballots, consensus was achieved for the answers to all issues.A formal consensus-based partnership between urology and radiation oncology to support newly diagnosed prostate cancer patients was feasible and resulted in a patient information guide which may improve decision-making.