Predictors of Tumor Dynamics Over a 6-Week Course of Concurrent Chemoradiotherapy for Glioblastoma and the Effect on Survival.

PURPOSE: We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study. METHODS AND MATERIALS: This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (Vrel) and tumor migration distance (dmigration). Covariables evaluated included: corpus callosum involvement, extent of surgery, O6-methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status. RESULTS: The median Vrel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median dmigration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant Vrel reduction at F20 (P = .03) and smaller dmigration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant Vrel reduction at F10 (P = .001) and F20 (P = .001) and a smaller dmigration at F10 (P = .03) and F20 (P = .002). O6-Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with Vrel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with dmigration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007). CONCLUSIONS: Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS.

Urethra contouring on computed tomography urethrogram versus magnetic resonance imaging for stereotactic body radiotherapy in prostate cancer.

Accurate urethra contouring is critical in prostate SBRT. We compared urethra contouring on CT-urethrogram and T2-weighted MRI. The dice similarity coefficient, Jaccard index, Hausdorff distance and mean distance to agreement were evaluated. All four metrics indicate better agreement and less variability in urethra contouring on CT-urethrogram, compared to T2-weighted MRI.

Management and outcomes of glioblastoma: 20-year experience in a single Australian institution.

INTRODUCTION: We aimed to evaluate the changing patterns in the management of glioblastoma (GBM) and impact on survival outcomes over a 20-year period. METHODS: This is a retrospective study of patients diagnosed with GBM between 2001 and 2020, who had radiation therapy (RT) in an Australian institution. The primary outcomes were changes in treatment modalities (including surgery, RT, and chemotherapy) over time and overall survival (OS). Multivariable Cox regressions were used to evaluate factors associated with OS, including age, sex, ECOG performance status, treatment modalities, treatment facility, and year of treatment. RESULTS: 1079 patients were included in this study. Thirty-five per cent of patients had gross total resection, increasing from 31% in 2001-2005 to 45% in 2016-2020 (P < 0.001). Sixty-four per cent of patients had ≥60 Gy RT, increasing from 57% in 2001-2005 to 66% in 2016-2020 (P < 0.001). Seventy-five per cent of patients had chemotherapy, increasing from 22% in 2001-2005 to 89% in 2016-2020 (P < 0.001). Treatment received varied based on patients' age and ECOG performance status. The median OS for the entire cohort was 13.0 months (95% CI = 12.0-13.7). Median OS in patients who had maximal treatment (i.e., gross total resection, ≥60 Gy RT and chemotherapy) was 20.6 months (95% CI = 17.3-22.8). In multivariable analyses, age, sex, treatment facility, extent of surgical resection, RT dose, and chemotherapy use were associated with OS. CONCLUSION: This is one of the largest Australian series on the management and outcomes of GBM spanning a 20-year period. We observed improvement in OS over time, which is likely associated with evolving treatment options over the study period.

Barriers and enablers of active surveillance for prostate cancer: a qualitive study of clinicians.

OBJECTIVES: To identify and explore barriers to, and enablers of, active surveillance (AS) in men with low-risk prostate cancer (LRPCa), as perceived by PCa clinicians. PATIENTS AND METHODS: Urologists and radiation oncologists in Australia and New Zealand were purposively sampled for a cross-section on gender and practice setting (metropolitan/regional; public/private). Using a grounded theory approach, semi-structed interviews were conducted with participants. Interviews were coded independently by two researchers using open, axial, and selective coding. A constant comparative approach was used to analyse data as it was collected. Thematic saturation was reached after 18 interviews, and a detailed model of barriers to, and enablers of, AS for LRPCa, as perceived by clinicians was developed. RESULTS: A model explaining what affects clinician decision making regarding AS in LRPCa emerged. It was underpinned by three broad themes: (i) clinician perception of patients' barriers and enablers; (ii) clinician perception of their own barriers and enablers; and (iii) engagement with healthcare team and resource availability. CONCLUSIONS: Clinicians unanimously agree that AS is an evidence-based approach for managing LRPCa. Despite this many men do not undergo AS for LRPCa, which is due to the interplay of patient and clinician factors, and their interaction with the wider healthcare system. This study identifies strategies to mitigate barriers and enhance enablers, which could increase access to AS by patients with LRPCa.

Prostate-Specific Antigen Response to Androgen Deprivation Therapy in the Neoadjuvant Setting for High-Risk Prostate Adenocarcinoma (PIRANHA): Pooled Analysis of Two Randomized Clinical Trials.

PURPOSE: A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiation therapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor signaling. This in turn may portend worse long-term clinical outcomes, especially in men with high-risk disease. We set out to evaluate the prognostic impact of poor PSA response to neoadjuvant ADT in men with high-risk prostate cancer. METHODS AND MATERIALS: This was a post hoc analysis of the multicenter TROG 03.04 RADAR and PCS IV randomized clinical trials. Inclusion criteria for this analysis were patients with high-risk prostate cancer (defined as Gleason score ≥8, initial PSA ≥20 ng/mL, or cT3a disease or higher) who received definitive radiation therapy, at least 18 months of ADT, and had a preradiation therapy PSA level drawn after at least 3 months of neoadjuvant ADT. Poor PSA response was defined as PSA >0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival, biochemical recurrence, prostate-cancer specific mortality, and overall survival. RESULTS: Nine hundred thirty men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89-154 months). After a median of 3 months (IQR, 3-4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29-1.59). Overall, 535 men (57%) had a PSA >0.5 ng/mL. Poor PSA response was associated with significantly worse metastasis-free survival (hazard ratio [HR], 3.93; P = .02), worse biochemical recurrence (subdistribution HR, 2.39; P = .003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P = .005), and worse overall survival (HR, 4.51; P = .05). CONCLUSIONS: Patients with PSA >0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification.

The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer-Quo Vadimus?

PURPOSE: Stereotactic body radiotherapy (SBRT) is an emerging treatment option for localized prostate cancer. There is increasing interest to reduce the number of fractions for prostate SBRT. METHODS: We provide a narrative review and summary of prospective trials of different fractionation schedules for prostate SBRT, focusing on efficacy, toxicities, and quality of life outcomes. RESULTS: There are two randomized phase 3 trials comparing standard external beam radiotherapy with ultra-hypofractionated radiotherapy. HYPO-RT-PC compared 78 Gy in 39 fractions vs 42.7 Gy in 7 fractions (3D-CRT or IMRT) showing non-inferiority in 5-year biochemical recurrence-free survival and equivalent tolerability. PACE-B trial compared 78 Gy in 39-fraction or 62 Gy in 20-fraction vs 36.25 Gy in 5-fraction prostate SBRT, with no significant differences in toxicity outcomes at 2 years. Five-year efficacy data for PACE-B are expected in 2024. Five-fraction prostate SBRT is currently the most common and well-established fractionation schedule with multiple prospective phase 2 trials published to date. There is more limited data on 1-4 fraction prostate SBRT. All fractionation schedules had acceptable toxicity outcomes. Experience from a high-dose-rate brachytherapy randomized trial showed inferior efficacy with single-fraction compared to two-fraction brachytherapy. Hence, caution should be applied in adopting single-fraction prostate SBRT. CONCLUSION: Two-fraction SBRT is likely the shortest fractionation schedule that maintains the therapeutic ratio. Several randomized trials currently recruiting will likely provide us with more definite answers about whether two-fraction prostate SBRT should become a standard-of-care option. Enrollment of eligible patients into these trials should be encouraged.

Population-based patient-reported quality of life outcomes following low-dose-rate versus high-dose-rate brachytherapy monotherapy for low-intermediate risk prostate cancer.

INTRODUCTION: To evaluate patient reported quality of life outcomes (QoL) following low-dose-rate brachytherapy (LDR-BT) and high-dose-rate brachytherapy (HDR-BT) monotherapy for prostate cancer at a population-based setting. METHODS: The study comprised men with low-intermediate risk prostate cancer in the Prostate Cancer Outcomes Registry Victoria (PCOR-Vic), who were treated with LDR-BT or HDR-BT monotherapy between 2015 and 2020 and completed the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire 12-month post-treatment. Men who had ADT were excluded (n = 12). Differences in substantial symptoms (i.e. 'moderate' or 'big' problem on a 5-point Likert scale) between LDR-BT and HDR-BT arms were evaluated using Pearson's chi-squared test. Multivariable linear regressions were used to estimate differences in EPIC-26 urinary, bowel and sexual functional domain scores between LDR-BT and HDR-BT arms. RESULTS: Overall, 198 men were included in this study, of which 167 (84%) had LDR-BT and 31 (16%) had HDR-BT. 9 (4.6%), 10 (5.1%) and 56 (28%) reported substantial symptoms for overall urinary, bowel and sexual function at 12-month post-treatment, with no significant difference between LDR-BT and HDR-BT arms. The adjusted mean differences in urinary incontinence, urinary obstructive, bowel and sexual function domain scores between LDR-BT and HDT-BT were: -3.53 (-8.21 to 1.14), -1.27 (-6.88 to 4.35), -0.01 (-5.63 to 5.63) and -8.68 (-21.44 to 4.07) respectively - these were not statistically significant and did not meet the minimal clinically important difference. CONCLUSION: This is the first Australian population-based study comparing QoL in men who had LDR-BT and HDR-BT, with no statistically or clinically significant differences in QoL observed at 12-month post-treatment.

Long-Term Quality-of-Life Outcomes After Prostate Radiation Therapy With or Without High-Dose-Rate Brachytherapy Boost: Post Hoc Analysis of TROG 03.04 RADAR.

PURPOSE: Adding high-dose-rate brachytherapy (BT) boost to external beam radiation therapy (EBRT) improves biochemical control but may affect patient-reported quality of life (QOL). We sought to determine long-term QOL outcomes for EBRT+BT versus EBRT alone. METHODS AND MATERIALS: This was a post hoc analysis of the Trans-Tasman Radiation Oncology Group 03.04 Randomized Androgen Deprivation and Radiotherapy (TROG 03.04 RADAR) trial. Only patients who received 74 Gy conventionally fractionated EBRT (n = 260) or 46 Gy conventionally fractionated EBRT plus 19.5 Gy in 3 fractions high-dose-rate BT boost (n = 237) were included in this analysis. The primary endpoint was patient-reported QOL measured using the European Organisation for Research and Treatment of Cancer QOL (EORTC QLQ-C30) and prostate-specific QOL module (EORTC QLQ-PR25) questionnaires. We evaluated temporal changes in QOL scores, rates of symptom resolution, and the proportion of men who had decrements from baseline of >2 × the threshold for minimal clinically important change (2 × MCIC) for each domain. RESULTS: At 5, 17, and 29 months after radiation therapy, the EBRT+BT group had 2.5 times (95% confidence interval [CI], 1.4-4.2; P < .001), 2.9 times (95% CI, 1.7-4.9; P < .001), and 2.6 times (95% CI, 1.4-4.6; P = .002) greater odds of reporting 2 × MCIC in urinary QOL score compared with EBRT. There were no differences beyond 29 months. EBRT+BT led to a slower rate of urinary QOL symptom score resolution up to 17 months after radiation therapy compared with EBRT (P < .001) but not at later intervals. In contrast, at the end of the radiation therapy period and at 53 months after radiation therapy, the EBRT+BT group had 0.65 times (95% CI, 0.44-0.96; P = .03) and 0.51 times (95% CI, 0.32-0.79; P = .003) the odds of reporting 2 × MCIC in bowel QOL symptom scores compared with EBRT. There were no significant differences in the rate of bowel QOL score resolution. There were no significant differences in global health status or sexual activity scores between the 2 groups. CONCLUSIONS: There were no persistent differences in patient-reported QOL measures between EBRT alone and EBRT+BT. BT boost does not appear to negatively affect long-term, patient-reported QOL.

Stereotactic Body Radiation Therapy for Spine Metastases-Findings from an Australian Population-Based Study.

Background: To evaluate the use of stereotactic body radiation therapy (SBRT) for spine metastases and the associated factors in Australia. Methods: The Victorian Radiotherapy Minimum Dataset, which captures all episodes of radiotherapy delivered in the state of Victoria, was accessed to evaluate the patterns and trends of SBRT for spine metastases. The primary outcome was SBRT use and associated factors. Results: There were 6244 patients who received 8861 courses of radiotherapy for spine metastases between 2012 and 2017. Of these, 277 (3%) courses were SBRT, which increased from 0.4% in 2012 to 5% in 2017 (P-trend < 0.001). There was a higher proportion of SBRT use in patients with prostate cancer (6%) and melanoma (4%) compared to other cancers (2-3%) (p < 0.001). Patients from the highest socioeconomic quintiles (5%) were more likely to be treated with SBRT compared to patients from the lowest socioeconomic quintiles (3%) (p < 0.001). There was a higher proportion of SBRT use in private radiotherapy centres (6%) compared to public radiotherapy centres (1%) (p < 0.001). No spine SBRT was delivered in regional centres. In multivariate analyses, the year of treatment, age, primary cancers and radiotherapy centres were independently associated with SBRT use. Conclusion: This is the first Australian population-based study quantifying the increasing use of spine SBRT; however, the overall use of spine SBRT remains low. We anticipate an ongoing increase in spine SBRT, as spine SBRT gradually becomes the standard-of-care treatment for painful spine metastases.

Dosimetric correlates of toxicities and quality of life following two-fraction stereotactic ablative radiotherapy (SABR) for prostate cancer.

PURPOSE: There is no evidence-based data to guide dose constraints in two-fraction prostate stereotactic ablative radiotherapy (SABR). Using individual patient-data from two prospective trials, we aimed to correlate dosimetric parameters with toxicities and quality of life (QoL) outcomes. MATERIALS AND METHODS: We included 60 patients who had two-fraction prostate SABR in the 2STAR (NCT02031328) and 2SMART (NCT03588819) trials. The prescribed dose was 26 Gy to the prostate+/-32 Gy boost to the dominant intraprostatic lesions. Toxicities and QoL data were prospectively collected using CTCAEv4 and EPIC-26 questionnaire. The outcomes evaluated were acute and late grade ≥ 2 toxicities, and late minimal clinical important changes (MCIC) in QoL domains. Dosimetric parameters for bladder, urethra, rectum, and penile bulb were evaluated. RESULTS: The median follow-up was 56 months (range: 39-78 months). The cumulative incidence of grade ≥ 2 genitourinary (GU), gastrointestinal (GI), and sexual toxicities were 62%, 3%, and 17% respectively in the acute setting (<3 months), and 57%, 15%, and 52% respectively in late setting (>6 months). There were 36%, 28%, and 29% patients who had late MCIC in urinary, bowel and sexual QoL outcomes respectively. Bladder 0.5 cc was significant predictor for late grade ≥ 2 GU toxicities, with optimal cut-off of 25.5 Gy. Penile bulb D5cc was associated of late grade ≥ 2 sexual toxicities (no optimal cut-off was identified). No dosimetric parameters were identified to be associated with other outcomes. CONCLUSION: Using real-life patient data from prospective trials with medium-term follow-up, we identified additional dose constraints that may mitigate the risk of late treatment-related toxicities for two-fraction prostate SABR.

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate.

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

To Boost or Not to Boost: Pooled Analyses From 2-Fraction SABR Trials for Localized Prostate Cancer.

PURPOSE: Focal boost to dominant intraprostatic lesion (DIL) is an approach for dose escalation in prostate radiation therapy. In this study, we aimed to report the outcomes of 2-fraction SABR ± DIL boost. METHODS AND MATERIALS: We included 60 patients with low- to intermediate-risk prostate cancer enrolled in 2 phase 2 trials (30 patients in each trial). In the 2STAR trial (NCT02031328), 26 Gy (equivalent dose in 2-Gy fractions = 105.4 Gy) was delivered to the prostate. In the 2SMART trial (NCT03588819), 26 Gy was delivered to the prostate, with up to 32 Gy boost to magnetic resonance imaging-defined DIL (equivalent dose in 2-Gy fractions = 156.4 Gy). The reported outcomes included prostate-specific antigen (PSA) response (ie, <0.4 ng/mL) at 4 years (4yrPSARR), biochemical failure (BF), acute and late toxicities, and quality of life (QOL). RESULTS: In 2SMART, median DIL D99% of 32.3 Gy was delivered. Median follow-up was 72.7 months (range, 69.1-75.) in 2STAR and 43.6 months (range, 38.7-49.5) in 2SMART. The 4yrPSARR was 57% (17/30) in 2STAR and 63% (15/24) in 2SMART (P = 0.7). The 4-year cumulative BF was 0% in 2STAR and 8.3% in 2SMART (P = 0.1). The 6-year BF in 2STAR was 3.5%. For genitourinary toxicities, there were differences in grade ≥1 urinary urgency in the acute (0% vs 47%; P < .001) and late settings (10% vs 67%; P < .001) favoring 2STAR. For urinary QOL, no difference was observed in the acute setting, but lower proportion in 2STAR had minimal clinically important changes in urinary QOL score in the late setting (21% vs 50%; P = .03). There were no significant differences in gastrointestinal and sexual toxicities and QOL in both acute and late settings between the 2 trials. CONCLUSIONS: This study presents the first prospective data comparing 2-fraction prostate SABR ± DIL boost. The addition of DIL boost resulted in similar medium-term efficacy (in 4yrPSARR and BF), with impact on late urinary QOL outcomes.

Real-world data on patterns and outcomes of radiation therapy for brain metastases in a population-based cohort of lung cancer patients in Victoria.

INTRODUCTION: We evaluated real-world data on the patterns and outcomes of radiotherapy (RT) for brain metastases (BM) in a population-based cohort of patients with lung cancer (LC) in Victoria. METHODS: The Victorian Radiotherapy Minimum Data set (VRMDS) and the Victorian Cancer Registry (VCR) were linked to identify patients with LC who underwent RT for BM between 2013 and 2016. We determined: (i) proportion of patients treated with stereotactic radiosurgery (SRS); (ii) overall survival (OS); and (iii) 30-day mortality (30M) following RT for BM. RESULTS: Of the 1001 patients included in the study, 193 (19%) had SRS. There was no significant increase in SRS use over time - from 18% in 2013 to 21% in 2016 (P-trend = 0.8). In multivariate analyses, increased age (P = 0.03) and treatment in regional centres (P < 0.001) were independently associated with lower likelihood of SRS treatment. The median OS following RT for BM was 3.6 months. Patients who had SRS had better OS than those who did not have SRS (median OS 8.9 months vs. 3 months, P < 0.01). SRS use, age, sex and year of treatment were independently associated with OS in multivariate analyses. A total of 184 (18%) patients died within 30 days of RT for BM, and the proportion was higher in older (P = 0.001) and male patients (P = 0.004). CONCLUSION: One-in-five LC patients who received RT for BM had SRS. The improved OS with SRS is likely confounded by patient selection. It is important to reduce 30M by better selecting patients who may not benefit from RT for BM.

Stereotactic Body Radiation Therapy for Spinal Metastases: Benefits and Limitations.

Progress in biological cancer characterization, targeted systemic therapies and multimodality treatment strategies have shifted the goals of radiotherapy for spinal metastases from short-term palliation to long-term symptom control and prevention of compilations. This article gives an overview of the spine stereotactic body radiotherapy (SBRT) methodology and clinical results of SBRT in cancer patients with painful vertebral metastases, metastatic spinal cord compression, oligometastatic disease and in a reirradiation situation. Outcomes after dose-intensified SBRT are compared with results of conventional radiotherapy and patient selection criteria will be discussed. Though rates of severe toxicity after spinal SBRT are low, strategies to minimize the risk of vertebral compression fracture, radiation induced myelopathy, plexopathy and myositis are summarized, to optimize the use of SBRT in multidisciplinary management of vertebral metastases.

Two-fraction stereotactic ablative radiotherapy with simultaneous boost to MRI-defined dominant intra-prostatic lesion - Results from the 2SMART phase 2 trial.

PURPOSE: This is the first report of the 2SMART Phase II trial evaluating the safety of two-fraction stereotactic ablative radiotherapy (SABR) with focal boost to magnetic resonance imaging (MRI) defined dominant intra-prostatic lesion (DIL) for localised prostate cancer. MATERIALS AND METHODS: Men with low or intermediate risk prostate cancer were eligible for the study. The gross tumour volume (GTV) was MRI-defined DIL, and the clinical target volume (CTV) was entire prostate gland. The planning target volume (PTV) was a 2 mm expansion anteroposterior and lateral, and 2.5 mm superoinferior. The prescribed dose was 32 Gy to GTV, and 26 Gy to CTV. Primary endpoint was minimal clinically important change (MCIC) in quality of life (QOL) within 3-months of SABR, assessed using the EPIC-26 questionnaire. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), PSA nadir, and biochemical failure (based on Phoenix criteria). RESULTS: Thirty men were enrolled in the study - 2 (7%) had low-risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range:39-49 months). The median PSA nadir was 0.25 ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. Ten (33%), six (20%), and three (10%) men had acute MCIC in urinary, bowel, and sexual QOL domains respectively. No acute or late grade ≥ 3 urinary or bowel toxicities were observed. CONCLUSION: This novel protocol of two-fraction prostate SABR with MRI-defined DIL boost is a safe approach for dose-escalation, with minimal impact on acute QOL and no grade ≥ 3 toxicities.

Late, persistent, substantial treatment-related symptoms (LAPERS) following low-dose-rate brachytherapy for prostate cancer.

PURPOSE: We aim to report 1) prevalence, 2) incidence, and 3) late, persistent, substantial treatment-related symptoms (LAPERS) after low-dose-rate brachytherapy (LDRBT) for prostate cancer. METHODS AND MATERIALS: The study comprised men treated with LDRBT in a single Australian institution between 2014 and 2019. All men completed the Expanded Prostate Cancer Index Composite 26 (EPIC-26) questionnaire pretreatment, and at regular intervals posttreatment. 'Substantial' symptoms were defined as 'moderate' or 'big' problems in EPIC-26 which assesses the degree of symptom bother for each functional domain. 'Persistent' symptoms were defined as 'substantial' symptoms that present in at least half of the 'late' followup assessments. This provided a binary LAPERS outcome (yes/no). Prevalence (at each time point) and cumulative incidence of substantial symptoms were also reported. RESULTS: A total of 172 men with 'baseline' and at least three 'late' followup EPIC-26 were included in the study. The median followup was 60 months (IQR: 36-74 months). For overall urinary function, prevalence of substantial symptoms was highest at 10% 6-month posttreatment, with 5-year cumulative incidence of 18%, but only 2% had LAPERS. For overall bowel function, prevalence of substantial symptoms was highest at 7% 12-months posttreatment, with 5-year cumulative incidence of 15%, and only 2% had LAPERS. For sexual function, prevalence of substantial symptoms was highest at 28% 6-months posttreatment, with 5-year cumulative incidence of 49%, and 22% had LAPERS (baseline-adjusted LAPERS 17%). CONCLUSIONS: There were considerable differences in late toxicities using different toxicity-reporting approaches. LAPERS approach is more reflective of 'true' late toxicities considering duration and persistence of symptoms.

Modern Active Surveillance in Prostate Cancer: A Narrative Review.

The use of PSA screening has led to downstaging and downgrading of prostate cancer at diagnosis, increasing detection of indolent disease. Active surveillance aims to reduce over-treatment by delaying or avoiding radical treatment and its associated morbidity. However, there is not a consensus on the selection criteria and monitoring schedules that should be used. This article aims to summarize the evidence supporting the safety of active surveillance, the current selection criteria recommended and in use, the incidence of active surveillance, barriers existing to its uptake and future developments in patient selection.

Comprehensive review of the use of hydrogel spacers prior to radiation therapy for prostate cancer.

OBJECTIVES: To provide a comprehensive narrative review of the published data on the impact of hydrogel spacers on rectal dosimetry and toxicity and to outline the practicalities of inserting hydrogel spacers. RESULTS: A growing body of evidence suggests that the administration of hydrogel spacers is safe and is associated with limited peri-operative morbidity. The impact on rectal dosimetry has been clearly established and use of hydrogel spacers is associated with reduced rectal morbidity. These results have been corroborated by several Phase II and III clinical trials and subsequent meta-analysis. There are several areas for future research, including the role of hydrogel spacers in prostate stereotactic beam radiotherapy and post-radiotherapy local recurrence. CONCLUSIONS: Hydrogel spacers provide a low-morbidity method to potential reduce rectal toxicity after radiation therapy in men with prostate cancer. Data outlining sexual function and oncological outcomes are limited to date. Future studies, currently being conducted, may provide further clarification of the role of hydrogel spacers in prostate cancer management.

Large variation in radiation therapy fractionation for multiple myeloma in Australia.

AIM: To evaluate the patterns of use of different radiation therapy (RT) fractionation for multiple myeloma (MM) bone disease. METHODS: This is a population-based cohort of patients with MM who had RT between 2012 and 2017 as captured in the statewide Victorian Radiotherapy Minimum Data Set in Australia. Data linkage was performed to identify subsets of RT delivered within 3 months of death. RT fractionation was classified into four groups: single-fraction (SFRT), 2-5, 6-10, and > 10 fractions. Changes in RT fractionation use over time were evaluated with the Cochran-Armitage test for trend. Factors associated with RT fractionation were evaluated using multivariate logistic regressions. RESULTS: Nine hundred and sixty-seven courses of RT were delivered in 623 patients. The proportion of SFRT, 2-5, 6-10 and > 10 fractions RT was 18%, 47%, 28%, and 7%, respectively. There was an increase in the use of 2-5 fractions, from 48% in 2012 to 60% in 2017 (p-trend < .001), with corresponding decrease in the use of 6-10 fractions, from 26% in 2012 to 20% in 2017 (p-trend = .003). Nine percent (40/430) of RT courses at private institutions were SFRT, compared to 25% (135/537) in public institutions (p < .001). In multivariate analyses, treatment in private institution was the strongest predictor of multifraction RT use. SFRT use was more common closer to the end of life-18%, 14%, and 33% of RT within 2-3, 1-2, < 1 month of death, respectively. CONCLUSION: There is increasing use of shorter course RT (2-5 fractions) for MM over time. SFRT use remains low, with large variation in practice.