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The article discusses the historical practice of using large clinical target volume (CTV) margins in the treatment of glioblastoma (GBM) and explores the possibility of reducing these margins. The traditional approach in North America has been to employ large CTV margins to account for potential geographical misses, but recent studies have shown that reducing the margins does not increase the risk of failure. The article supports the use of a 1.5-cm CTV expansion beyond the gross tumor volume (GTV) and emphasizes the importance of MRI guidance in further reducing the CTV margin. The findings suggest that using smaller margins can spare healthy brain tissue and improve quality of life for patients. [Extracted from the article]

Although spine stereotactic body radiation therapy (SBRT) is considered a standard of care in the mobile spine, mature evidence reporting outcomes specific to sacral metastases is lacking. Furthermore, there is a need to validate the existing sacral SBRT international consensus contouring guidelines to define the optimal contouring approach. We report mature rates of local failure (LF), adverse events, and the effect of contouring deviations in the largest experience to date specific to sacrum SBRT. Consecutive patients who underwent sacral SBRT from 2010 to 2021 were retrospectively reviewed. The primary endpoint was magnetic resonance imaging–based LF with a focus on adherence to target volume contouring recommendations. Secondary endpoints included vertebral compression fracture and neural toxicity. Of the 215 sacrum segments treated in 112 patients, most received 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Sixteen percent of segments were nonadherent to the consensus guideline with a more restricted target volume (undercontoured). The median follow-up was 21.4 months (range, 1.5-116.9 months). The cumulative incidence of LF at 1 and 2 years was 18.4% and 23.1%, respectively. In those with guideline adherent versus nonadherent contours, the LF rate at 1 year was 15.1% versus 31.4% and at 2 years 18.8% versus 40.0% (hazard ratio [HR], 2.5; 95% CI, 1.4-4.6; P =.003), respectively. On multivariable analysis, guideline nonadherence (HR, 2.4; 95% CI, 1.3-4.7; P =.008), radioresistant histology (HR, 2.4; 95% CI, 1.4-4.1; P <.001), and extraosseous extension (HR, 2.5; 95% CI, 1.3-4.7; P =.005) predicted for an increased risk of LF. The cumulative incidence of vertebral compression fracture was 7.1% at 1 year and 12.3% at 2 years. Seven patients (6.3%) developed peripheral nerve toxicity, of whom 4 had been previously radiated. Sacral SBRT is associated with high efficacy rates and an acceptable toxicity profile. Adhering to consensus guidelines for target volume delineation is recommended to reduce the risk of LF. [ABSTRACT FROM AUTHOR]

Purpose: We report mature outcomes for a cohort of patients with no prior radiation (de novo) to the spine treated with 24 Gy in 2 daily fractions for metastases, which represents the same stereotactic body radiation therapy (SBRT) regimen under evaluation in the current Symptom Control-24 phase 3 randomized trial (NCT02512965).Methods and Materials: The cohort consisted of 279 de novo spinal metastases in 145 consecutive patients treated with 24 Gy in 2 SBRT fractions, identified from a prospective single-institution database. The endpoints were overall survival (OS), imaging-based local failure (LF), and cumulative risk of vertebral compression fractures (VCF).Results: The median follow-up per treated metastasis was 15.0 months (range, 0.1-71.6). The 1-year and 2-year OS rates were 73.1% and 60.7%, respectively. Presence of epidural disease (P < .0001), lung (P = .0415), and renal cell (P < .0001) primary histologies and baseline diffuse metastases (P = .0034) were significant prognostic factors for OS. The 1-year and 2-year LF rates were 9.7% and 17.6%, respectively, and the median time to LF was 9.2 month (range, 0.4-31.3 months). Only the presence of epidural disease predicted for LF (P < .0001). The cumulative risk of VCF at 1 and 2 years was 8.5% and 13.8%, respectively. Lytic (P = .0143) or mixed lytic/blastic (P = .0214) lesions, spinal malalignment (P = .0121), and the dose to 90% of the planning target volume (P = .0085) were significant predictors for VCF.Conclusions: Twenty-four Gray in 2 daily fractions is safe and effective in achieving high tumor control rates for de novo spinal metastases. These outcomes will serve as a benchmark for the ongoing Symptom Control-24 randomized trial comparing 24 Gy in 2 SBRT fractions to 20 Gy delivered in 5 daily conventional fractions. [ABSTRACT FROM AUTHOR]

Background and purpose We aimed to investigate the suitability of treating patients with single brain metastases using stereotactic radiosurgery (SRS) with the MRL and to characterize the dosimetric impact at tissue-air interfaces resulting primarily from the electron return effect (ERE). Material and methods 24 patients treated for intact single brain metastases were analyzed. Three radiotherapy plans with the same prescribed dose were generated for each case: (1) noncoplanar volumetric modulated arc therapy (VMAT), (2) coplanar step-and-shoot intensity modulated radiotherapy (IMRT) on the MRL in the absence (MRLB=0), and (3) in the presence of the transverse magnetic field (MRLB=1.5). The plans were evaluated using cumulative dose–volume histograms and by calculation of Paddick conformity index (CI), V100%, V12Gy minus gross tumor volume (V12Gy – GTV), and V2Gy. At tissue-air boundaries, the dosimetric impact of the magnetic field was quantified using a 5 mm rim of tissue. Results All plans met the target coverage and organs-at-risk planning objectives. Differences between all investigated dosimetric parameters significantly favored the VMAT plans as compared to the MRLB=0 and MRLB=1.5 plans, except for V2Gy. The mean V12Gy – GTV and V2Gy marginally favored the MRLB=0 plans compared to the MRLB=1.5 plans (mean difference: 0.45 cm 3 , p  = 0.0019 and 16.46 cm 3 , p  < 0.0001, respectively). The presence of the magnetic field resulted in a statistically significant but small increase in mean dose and D 2cc in the skin (0.08 Gy, p  < 0.0001 and 0.6 Gy, p  < 0.0001, respectively) and around air cavities (0.07 Gy, p  = 0.0092 and 0.3 Gy, p  = 0.0004, respectively). Conclusions It is feasible to generate stereotactic radiation plans that satisfy clinical requirements using the MRL in the setting of single brain metastases. The dosimetric impact of the magnetic field including the ERE at tissue-air boundaries is minor and does not negatively impact target conformity or dose gradient. [ABSTRACT FROM AUTHOR]

Purpose To assess motion of the spinal cord and cauda equina, which are critical neural tissues (CNT), which is important when evaluating the planning organ-at-risk margin required for stereotactic body radiation therapy. Methods and Materials We analyzed CNT motion in 65 patients with spinal metastases (11 cervical, 39 thoracic, and 24 lumbar spinal segments) in the supine position using dynamic axial and sagittal magnetic resonance imaging (dMRI, 3T Verio, Siemens) over a 137-second interval. Motion was segregated according to physiologic cardiorespiratory oscillatory motion (characterized by the average root mean square deviation) and random bulk shifts associated with gross patient motion (characterized by the range). Displacement was evaluated in the anteroposterior (AP), lateral (LR), and superior-inferior (SI) directions by use of a correlation coefficient template matching algorithm, with quantification of random motion measure error over 3 separate trials. Statistical significance was defined according to P <.05. Results In the AP, LR, and SI directions, significant oscillatory motion was observed in 39.2%, 35.1%, and 10.8% of spinal segments, respectively, and significant bulk motions in all cases. The median oscillatory CNT motions in the AP, LR, and SI directions were 0.16 mm, 0.17 mm, and 0.44 mm, respectively, and the maximal statistically significant oscillatory motions were 0.39 mm, 0.41 mm, and 0.77 mm, respectively. The median bulk displacements in the AP, LR, and SI directions were 0.51 mm, 0.59 mm, and 0.66 mm, and the maximal statistically significant displacements were 2.21 mm, 2.87 mm, and 3.90 mm, respectively. In the AP, LR, and SI directions, bulk displacements were greater than 1.5 mm in 5.4%, 9.0%, and 14.9% of spinal segments, respectively. No significant differences in axial motion were observed according to cord level or cauda equina. Conclusions Oscillatory CNT motion was observed to be relatively minor. Our results support the importance of controlling bulk patient motion and the practice of applying a planning organ-at-risk margin. [ABSTRACT FROM AUTHOR]

Abstract: Heat transfer in a photoelectrochemical (PEC) hydrogen generation reactor system is studied numerically. Four different reactor designs are investigated in this work. Solar irradiation is spectrally separated into short and long wavelength parts depending on the energy band gap of the photoelectrode. The short wave energy is directed to the anode to generate electron and hole pairs, and the long wave energy is used for heating the reactor. Results indicate that the use of the excess long wave energy by careful reactor design can effectively increase the system efficiency. Comparing designs 1 and 4 under 6000 W/m2 irradiation and a quantum efficiency of 30%, the enhancement of the solar-to-hydrogen efficiency is respectively 12.7% and 18.2% for electrodes with E g  = 2.1 eV and 3.2 eV, such as Fe2O3 and TiO2. Effects of several parameters on the PEC hydrogen reactor system are discussed in details. [Copyright &y& Elsevier]

Abstract: The heat transfer and flow characteristics of a photoelectrochemical (PEC) hydrogen generation reactor are investigated numerically. Four different reactor designs are considered in this study. The solar irradiation is separated into short and long wavelength parts depending on the energy band gap of the photoelectrode used. While short wavelength part is used to generate electron and hole pairs, the long wavelength part is used to heat the system. Because the energy required for splitting water decreases as temperature is increased, heating the reactor by using the long wave energy increases the system efficiency. Thus, how the long wavelength energy is absorbed by the reactor is very important. The results show that more long wavelength energy kept inside the reactor can increase the solar-to-hydrogen efficiency, η SH. For Fe2O3 photoelectrode, careful reactor design can increase ηSH by 11.0%. For design D under 4000 W/m2 irradiation and a quantum efficiency of 30%, η SH is found to be 14.1% and the hydrogen volume production rate is 166 L/m2 h for Fe2O3. Effects of several parameters on the PEC hydrogen reactor are also discussed. [Copyright &y& Elsevier]

Abstract: The thermodynamic analysis of photoelectrochemical (PEC) hydrogen production is performed in this work for air mass 1.5 solar insolation. Because the energy required for splitting water decreases as temperature is increased, heating the system by using the long wavelength energy will increase the system efficiency. As the energy band gap of the photoelectrode increases, the induced photo-current is decreased. If photons absorbed are all excited, the maximum photo-current is 63.8mA/cm2. For TiO2 (∼3.2eV) and Fe2O3 (∼2.1eV), the maximum photo-current is respectively 0.68mA/cm2 and 10.4mA/cm2. The maximum power conversion efficiency of a PEC cell is 44.1%. For TiO2 and Fe2O3, the power conversion efficiency is 2.8% and 21.9%, respectively. At 647K and quantum efficiency=30%, the maximum hydrogen production rate is 7.5L/m2 h and 41.8L/m2 h for TiO2 and Fe2O3, and the maximum efficiency of solar to hydrogen is 2.71% and 14.2% for TiO2 and Fe2O3 respectively. In order to increase the maximum hydrogen production rate, it is more effective to raise the quantum efficiency than raising the reaction temperature. [Copyright &y& Elsevier]

Stereotactic body radiation therapy (SBRT) is increasingly being used to treat spine metastases. Current post-SBRT imaging surveillance strategies in this patient population may benefit from a more data-driven and personalized approach. The objective of this study was to develop risk-stratified post-SBRT magnetic resonance imaging (MRI) surveillance strategies using quantitative methods. Adult patients with bony spine metastases treated with SBRT between 2008 and 2021 and who had at least 2 follow-up spine MRIs were reviewed retrospectively. A recursive partitioning analysis model was developed to separate patients into different risk categories for post-SBRT progression anywhere within the spine. Imaging intervals were derived for each risk category using parametric survival regression based on multiple expected spine progression rates per scan. A total of 446 patients and 1039 vertebral segments were included. Cumulative incidence of spine progression was 19.2% at 1 year, 26.7% at 2 years, and 35.3% at 4 years. The internally validated risk stratification model was able to divide patients into 3 risk categories based on epidural disease, paraspinal disease, and Spinal Instability Neoplastic Score category. The 4-year risk of spine progression was 23.4%, 39.0%, and 51.8%, respectively, for the low-, intermediate-, and high-risk groups. Using an expected per-scan spine progression rate of 3.75%, the low-risk group would require follow-up scans every 6.0 months (95% CI, 4.9-7.6) and the intermediate-risk group would require surveillance every 3.1 months (95% CI, 2.6-3.7). At an expected spine progression rate of 5%, the high-risk group would require surveillance every 1.3 months (95% CI, 1.1-1.6) during the first 13.2 months after SBRT and every 5.9 months thereafter (95% CI, 2.8-12.3). Data-driven follow-up MRI surveillance intervals at a range of expected spine progression rates have been determined for patients at different risks of spine progression based on an internally validated, single-institution risk stratification model. [ABSTRACT FROM AUTHOR]

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. 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 (V rel) and tumor migration distance (d migration). Covariables evaluated included: corpus callosum involvement, extent of surgery, O6-methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status. The median V rel 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 d migration 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 V rel reduction at F20 (P =.03) and smaller d migration 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 V rel reduction at F10 (P =.001) and F20 (P =.001) and a smaller d migration 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 V rel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P =.001), and patients with d migration ≥ 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). 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. [ABSTRACT FROM AUTHOR]

Background: The radiotherapy process relies on several metrics in determining a notion of "distance" from one three‐dimensional region‐of‐interest (ROI) to another. The majority are symmetric (or commutative) and do not contain information pertaining to directionality. Growth versus regression, for example, is not inherently distinguished by these metrics. Purpose: The purpose of this work was to formalize a unidirectional distance metric, motivated by radiotherapy margin concepts, which we term the migration distance. Informally, the migration distance from ROI X$X$ to Y$Y$ is the minimum isotropic expansion of X$X$ such that Y$Y$ is completely encompassed by the expansion. If Y$Y$ is contained within X$X$, the migration distance is negative with magnitude equal to the maximum isotropic contraction of X$X$ such that Y$Y$ remains contained within contraction. The metric is demonstrated by quantifying glioblastoma interfraction target changes. Methods: An explicit mathematical formulation of the migration distance is presented and contrasted with the related Hausdorff distance. The results are demonstrated for the gross tumor volume (GTV) dynamics of a glioblastoma cohort consisting of 111 patients that underwent standard chemoradiotherapy with offline MR imaging at planning, fraction 10, fraction 20, and 1‐month post radiotherapy. Results: The mean ± SD of the GTV migration distance relative to planning was 5.9 ± 3.9 mm at fraction 10, 6.2 ± 4.4 mm at fraction 20, and 7.9 ± 7.1 mm at 1‐month post radiotherapy. The maximum GTV migration distance across all patients at the same timepoints was 20.4, 20.7, and 45.5 mm, respectively. Conclusions: We have proposed and demonstrated a unidirectional distance metric. The migration distance may have applications in the quantification of anatomical changes, planning target volume designs, and dosimetric radiotherapy plan assessment. [ABSTRACT FROM AUTHOR]

The aim of this work is to report on the results of a phase 2 randomized trial of moderately hypofractionated (MH) versus conventionally fractionated (CF) radiation therapy to the prostate with elective nodal irradiation. This was a single-center, prospective, phase 2 randomized study. Patients with high-risk disease (cT3, prostate-specific antigen level >20 ng/mL, or Gleason score 8-10) were eligible. Patients were randomized to either MH using a simultaneous integrated boost (68 Gy in 25 fractions to prostate; 48 Gy to pelvis) or CF (46 Gy in 23 fractions with a sequential boost to the prostate of 32 Gy in 16 fractions), with long-term androgen deprivation therapy. The primary endpoint was grade ≥2 acute gastrointestinal (GI) and genitourinary (GU) toxicity (Common Terminology Criteria for Adverse Events version 3.0). Secondary endpoints included late GI and GU toxicity, quality of life, and oncologic outcomes. One-hundred eighty patients were enrolled; 90 were randomized to and received MH and 90 to CF. The median follow-up was 67.4 months. Seventy-five patients (41.7%) experienced a grade ≥2 acute GI and/or GU toxicity, including 34 (37.8%) in the MH and 41 (45.6%) in the CF arms, respectively (P =.29). Late grade ≥2 GI (P =.07) and GU (P =.25) toxicity was not significantly different between arms; however, late grade ≥3 GI toxicity was worse in the MH group (P =.01). There were no statistically significant quality-of-life differences between the 2 treatments. There were no statistically significant differences observed in cumulative incidence of biochemical failure (P =.71) or distant metastasis (P =.31) and overall survival (P =.46). MH to the prostate and pelvis with androgen deprivation therapy for men with high-risk localized prostate cancer was not significantly different than CF with regard to acute toxicity, quality of life, and oncologic efficacy. However, late grade ≥3 GI toxicity was more common in the MH arm. [ABSTRACT FROM AUTHOR]

The optimal modern radiation therapy (RT) approach after surgery for atypical and malignant meningioma is unclear. We present results of dose escalation in a single-institution cohort spanning 2000 to 2021. Consecutive patients with histopathologic grade 2 or 3 meningioma treated with RT were reviewed. A dose-escalation cohort (≥66 Gy equivalent dose in 2-Gy fractions using an α/β = 10) was compared with a standard-dose cohort (<66 Gy). Outcomes were progression-free survival (PFS), cause-specific survival, overall survival (OS), local failure (LF), and radiation necrosis. One hundred eighteen patients (111 grade 2, 94.1%) were identified; 54 (45.8%) received dose escalation and 64 (54.2%) standard dose. Median follow-up was 45.4 months (IQR, 24.0-80.0 months) and median OS was 9.7 years (Q1: 4.6 years, Q3: not reached). All dose-escalated patients had residual disease versus 65.6% in the standard-dose cohort (P <.001). PFS at 3, 4, and 5 years in the dose-escalated versus standard-dose cohort was 78.9%, 72.2%, and 64.6% versus 57.2%, 49.1%, and 40.8%, respectively, (P =.030). On multivariable analysis, dose escalation (hazard ratio [HR], 0.544; P =.042) was associated with improved PFS, whereas ≥2 surgeries (HR, 1.989; P =.035) and older age (HR, 1.035; P <.001) were associated with worse PFS. The cumulative risk of LF was reduced with dose escalation (P =.016). Multivariable analysis confirmed that dose escalation was protective for LF (HR, 0.483; P =.019), whereas ≥2 surgeries before RT predicted for LF (HR, 2.145; P =.008). A trend was observed for improved cause-specific survival and OS in the dose-escalation cohort (P <.1). Seven patients (5.9%) developed symptomatic radiation necrosis with no significant difference between the 2 cohorts. Dose-escalated RT with ≥66 Gy for high-grade meningioma is associated with improved local control and PFS with an acceptable risk of radiation necrosis. [ABSTRACT FROM AUTHOR]

Because multiparametric MRI can generate detailed images of the anatomic extent of cancer within the prostate, its integration in salvage therapies such as brachytherapy has been widely embraced. It has enabled focal therapies and whole-gland therapies with intra-prostatic boost. The objectives of our prospective study is to investigate the efficacy and toxicities of MR-assisted whole-gland salvage HDR prostate brachytherapy with intra-prostatic boost in patients with local recurrent prostate cancer. Eligible patients included: multiparametric 3T MRI (mpMRI) visible biopsy confirmed local recurrence >30 months after XRT, negative metastatic workup, and IPSS <15. Ultrasound-based HDR brachytherapy with intraoperative contour-based deformable registration between the mpMRI and ultrasound images were done in 28 of 30 patients, and cognitive fusion in the remaining 2 patients. The prescription dose was 21Gy to the entire prostate and 27Gy to the MR-defined intraprostatic target volume (TV) divided over two implants separated by 1-2 weeks with dose constraints to the urethra and rectum. Adjuvant androgen deprivation therapy (ADT) was not used. Post-treatment response was evaluated using mpMRI 1-2 years after salvage. Follow-up PSA, IPSS and CTCAE v4.0 toxicities were collected. 30 patients (median age 74 years) were enrolled in the study. Median follow up from salvage HDR was 33 months (12-60). At initial presentation, there were 3, 18 and 9 low-, intermediate- and high-risk disease. The initial XRT dose was 70-78Gy with conventional fractionation in 28 patients and alternate fractionation in 2 patients (35Gy/5F and 50Gy/15F). Median time from initial treatment to biopsy-confirmed local recurrence was 9.3 years (2.4-17.6). The Gleason score of the local recurrence was 6, 7 and 8-10 in 2, 19 and 9, respectively. The pre-HDR median PSA was 3.67ng/mL (0.63-11.01). The median size of the prostate was 33.8 mL (15.9-86.0) and TV was 4.7mL (1.5-15.5). The median dosimetric endpoints per implant were: prostate V10.5Gy 96.5% (94.1-98.7), prostate D90 11.4Gy (10.9-12.0), TV V13.5Gy 94.2% (63.3-100), TV D90 18.1Gy (15.0-22.2), urethral D10% 12.0Gy (11.5-12.6), urethral Dmax 12.6Gy (12.2-13.5) and rectal V8.4Gy 0mL (0-0.8). Four patients (13%) required temporary urinary catheterization. There were no acute/late GU/GI grade 3-5 toxicities. The most common acute toxicity was frequency, dysuria and urgency. Mean IPSS at baseline, 1.5-, 3-, 6-, 9-, 12-, 18-, 24-, 30- and 36-months was 6, 15, 10, 11, 10, 12, 10, 10, 9 and 7, respectively (p=0.03). Three-year PSA progression-free survival and freedom from ADT rate was 67% and 93%, respectively. Of the 26 patients who had a post-HDR MRI (median 415 days), 18 (69%) patients had a complete response and 8 had persistent disease in the TV. No patients recurred elsewhere in the prostate. Our toxicity, IPSS and PSA failure-free results suggests that whole gland salvage HDR brachytherapy with intra-prostatic boost is well tolerated and effective. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the dosimetric impact of using virtual couch shift (VCS) for correcting setup errors in glioblastoma multiforme (GBM) patients treated on a magnetic resonance imaging (MRI)-linac.Methods and Materials: Six GBM patients treated with 60 Gy (30 fractions) were selected for this simulation study. For each case, 2 reference plans were generated in the MRL treatment planning system: With (WIB) and with no (NOB) MRI B field present. Subsequently, 2-mm, 4-mm, and 6-mm translational errors were simulated and corrected for using a VCS method based on shift-only, warm start segment weight (SWO), and segment weight and shape (SSO) optimization. The resulting distributions were compared with the reference plan using planning target volume (PTV) homogeneity index (HI), conformity index (CI), organs at risk (OAR) maximum dose (D0.01cc), and OAR median dose (D50). A simulated 30-fraction treatment was constructed to evaluate the cumulative effect of daily corrections. Feasibility and workflow for correcting rotations were also assessed.Results: All reference plans were deemed clinically acceptable with respect to PTV and OAR objectives. The difference in HI (ΔHI) between corrected and reference was not statistically significant between WIB and NOB (P=.89). The average ΔHI was +0.8%, -0.1%, and -1.0% for shift-only, SWO, and SSO, respectively, with a statistically significant difference (P<.001) for shift-only versus SWO and SSO. The CI remained unchanged (mean ΔCI = -0.01) between the corrected and reference plans, with no statistically significant dependence on magnetic field presence, correction method, or shift magnitude or orientation. The brainstem D50 on average decreased with SWO and SSO; however, D0.01cc increased by a median value of 1.2%, 1.9%, and 2.0% for shift-only, SWO, and SSO, respectively. For other OARs, D0.01cc decreased using SWO or SSO. For the simulated treatment and rotational corrections, similar trends were measured.Conclusion: For translational errors in brain MRI-linac radiation therapy, the VCS method is an acceptable correction strategy, but caution must be used in particular for serial organs where maximum doses are most relevant. The effect of the magnetic field on relative changes between corrected versus reference plans is not clinically relevant. [ABSTRACT FROM AUTHOR]

Stereotactic body radiation therapy (SBRT) for spine metastases improves pain response rates compared with conventional external beam radiation therapy; however, the optimal fractionation schedule is unclear. We report local control and toxicity outcomes after dose-escalated 2-fraction spine SBRT. A prospectively maintained institutional database of over 600 patients and 1400 vertebral segments treated with spine SBRT was reviewed to identify those prescribed 28 or 24 Gy in 2 daily fractions. The primary endpoint was magnetic resonance imaging based local failure (LF), and secondary endpoints included overall survival and vertebral compression fracture (VCF). A total of 947 treated vertebral segments in 482 patients were identified, of which 301 segments in 159 patients received 28 Gy, and 646 segments in 323 patients received 24 Gy in 2 fractions. Median follow-up per patient was 23.5 months, and median overall survival was 49.1 months. In the 28 Gy cohort, the 6-, 12-, and 24-month cumulative incidences of LF were 3.5%, 5.4%, and 11.1%, respectively, versus 6.0%, 12.5%, and 17.6% in the 24 Gy cohort, respectively (P =.008). On multivariable analysis, 24 Gy (hazard ratio [HR], 1.525; 95% confidence interval, 1.039-2.238; P =.031), paraspinal disease extension (HR, 1.422; 95% confidence interval, 1.010-2.002; P =.044), and epidural extension in either radioresistant or radiosensitive histologies (HR, 2.117 and 1.227, respectively; P =.003) were prognostic for higher rates of LF. Risk of VCF was 5.5%, 7.6%, and 10.7% at 6, 12, and 24 months, respectively, and was similar between cohorts (P =.573). Spinal malalignment (P <.001), baseline VCF (P =.003), junctional spine location (P =.030), and greater minimum dose to 90% of planning target volume were prognostic for higher rates of VCF. Dose escalation to 28 Gy in 2 daily fractions was associated with improved local control without increasing the risk of VCF. The 2-year local control rates are consistent with those predicted by the Hypofractionated Treatment Effects in the Clinic spine tumor control probability model, and these data will inform a proposed dose escalation randomized trial. [ABSTRACT FROM AUTHOR]

Purpose: Target localization, for stereotactic radiosurgery (SRS) treatment with Gamma Knife, has become increasingly reliant on the co‐registration between the planning MRI and the stereotactic cone‐beam computed tomography (CBCT). Validating image registration between modalities would be particularly beneficial when considering the emergence of novel functional and metabolic MRI pulse sequences for target delineation. This study aimed to develop a phantom‐based methodology to quantitatively compare the co‐registration accuracy of the standard clinical imaging protocol to a representative MRI sequence that was likely to fail co‐registration. The comparative methodology presented in this study may serve as a useful tool to evaluate the clinical translatability of novel MRI sequences. Methods: A realistic human skull phantom with fiducial marker columns was designed and manufactured to fit into a typical MRI head coil and the Gamma Knife patient positioning system. A series of "optimized" 3D MRI sequences—T1‐weighted Dixon, T1‐weighted fast field echo (FFE), and T2‐weighted fluid‐attenuated inversion recovery (FLAIR)—were acquired and co‐registered to the CBCT. The same sequences were "compromised" by reconstructing without geometric distortion correction and re‐collecting with lower signal‐to‐noise‐ratio (SNR) to simulate a novel MRI sequence with poor co‐registration accuracy. Image similarity metrics—structural similarity (SSIM) index, mean squared error (MSE), and peak SNR (PSNR)—were used to quantitatively compare the co‐registration of the optimized and compromised MR images. Results: The ground truth fiducial positions were compared to positions measured from each optimized image volume revealing a maximum median geometric uncertainty of 0.39 mm (LR), 0.92 mm (AP), and 0.13 mm (SI) between the CT and CBCT, 0.60 mm (LR), 0.36 mm (AP), and 0.07 mm (SI) between the CT and T1‐weighted Dixon, 0.42 mm (LR), 0.23 mm (AP), and 0.08 mm (SI) between the CT and T1‐weighted FFE, and 0.45 mm (LR), 0.19 mm (AP), and 1.04 mm (SI) between the CT and T2‐weighted FLAIR. Qualitatively, pairs of optimized and compromised image slices were compared using a fusion image where separable colors were used to differentiate between images. Quantitatively, MSE was the most predictive and SSIM the second most predictive metric for evaluating co‐registration similarity. A clinically relevant threshold of MSE, SSIM, and/or PSNR may be defined beyond which point an MRI sequence should be rejected for target delineation based on its dissimilarity to an optimized sequence co‐registration. All dissimilarity thresholds calculated using correlation coefficients with in‐plane geometric uncertainty would need to be defined on a sequence‐by‐sequence basis and validated with patient data. Conclusion: This study utilized a realistic skull phantom and image similarity metrics to develop a methodology capable of quantitatively assessing whether a modern research‐based MRI sequence can be co‐registered to the Gamma Knife CBCT with equal or less than equal accuracy when compared to a clinically accepted protocol. [ABSTRACT FROM AUTHOR]

• Long-term outcomes of HDR brachytherapy for low and intermediate prostate cancer. • Treatment given as single 19 Gy fraction or two 13.5 Gy fractions, with 9-year follow-up. • We observed that two fractions of 13.5 Gy led to a robust, long-term PSA response with acceptable toxicity. • In contrast, a single fraction of 19 Gy yielded poor oncologic outcomes and is not recommended. • Contributes to the ongoing debate on optimal HDR monotherapy strategies to manage low and intermediate-risk prostate cancer. High dose-rate (HDR) brachytherapy as a monotherapy is an accepted treatment for localized prostate cancer, but the optimal dose and fractionation schedule remain unknown. We report on the efficacy of a randomized Phase II trial comparing HDR monotherapy delivered as 27 Gy in 2 fractions vs. 19 Gy in 1 fraction with a median follow-up of 9 years. Enrolled patients had low or intermediate-risk disease, <60 cc prostate volume and no androgen deprivation use. Patients were randomized to 27 Gy in 2 fractions delivered one week apart vs a single fraction of 19 Gy. 170 patients were randomized: median age 65 years, median follow-up 107 months and median baseline PSA 6.35 ng/ml. NCCN risk categories comprised low (19 %), favourable (51 %), and unfavourable intermediate risk (30 %). The median PSA at 8 years was 0.08 ng/ml in the 2-fraction arm vs. 0.89 ng/ml in the single-fraction arm. The cumulative incidence of local failure at 8 years was 11.2 % in the 2-fraction arm vs. 35.9 % in the single-fraction arm (p < 0.001). The incidence of distant failure at 8 years was 3.8 % in the 2-fraction arm and 2.5 % in the single-fraction arm (p = 0.6). HDR monotherapy delivered in two fractions of 13.5 Gy demonstrated a persistent cancer control rate at 8 years and was well-tolerated. Single-fraction monotherapy yielded poor oncologic control and is not recommended. These findings contribute to the ongoing discourse on optimal HDR monotherapy strategies for low and intermediate-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) improves complete pain response for painful spinal metastases compared with conventional external beam radiation therapy (cEBRT). We report mature local control and reirradiation rates in a large cohort of patients treated with SBRT versus cEBRT enrolled previously in the Canadian Clinical Trials Group Symptom Control 24 phase 2/3 trial.Methods and Materials: One hundred thirty-seven of 229 (60%) patients randomized to 24 Gy in 2 SBRT fractions or 20 Gy in 5 cEBRT fractions were retrospectively reviewed. By including all treated spinal segments, we report on 66 patients (119 spine segments) treated with SBRT and 71 patients (169 segments) treated with cEBRT. The primary outcomes were magnetic resonance-based local control and reirradiation rates for each treated spine segment.Results: The median follow-up was 11.3 months (interquartile range, 5.3-27.7 months), and median overall survival in the SBRT and cEBRT cohorts were 21.6 (95% confidence interval [CI], 11.3, upper bound not reached) and 18.9 (95% CI, 12.2-29.1) months (P = .428), respectively. The cohorts were balanced with respect to radioresistant histology and presence of mass (paraspinal and/or epidural disease extension). Risk of local failure after SBRT versus cEBRT at 6, 12, and 24 months were 2.8% (95% CI, 0.8%-7.4%) versus 11.2% (95% CI, 6.9%-16.6%), 6.1% (95% CI, 2.5%-12.1%) versus 28.4% (95% CI, 21.3%-35.9%), and 14.8% (95% CI, 8.2-23.1%) versus 35.6% (95% CI, 27.8%-43.6%), respectively (P < .001). cEBRT (hazard ratio [HR], 3.48; 95% CI, 1.94-6.25; P < .001) and presence of mass (HR, 2.07; 95% CI, 1.29-3.31; P = .002) independently predicted local failure on multivariable analysis. The 1-year reirradiation rates and median times to reirradiation after SBRT versus cEBRT were 2.2% (95% CI, 0.4-7.0%) versus 15.8% (95% CI, 10.4%-22.3%) (P = .002) and 22.9 months versus 9.5 months, respectively. cEBRT (HR, 2.60; 95% CI, 1.27-5.30; P = .009) and radioresistant histology (HR, 2.00; 95% CI, 1.12-3.60; P = .020) independently predicted for reirradiation. Eight of 12 iatrogenic vertebral compression fractures were after SBRT and 4 of 12 after cEBRT; grade 3 adverse fracture effects were isolated to the SBRT cohort (5 of 12).Conclusions: Risk of local failure and reirradiation is lower with SBRT compared with cEBRT for spinal metastases. Although the iatrogenic vertebral compression fracture rates were within expectations, grade 3 vertebral compression fractures were isolated to the SBRT cohort. [ABSTRACT FROM AUTHOR]

Purpose: We report our experience in salvaging spinal metastases initially irradiated with stereotactic body radiation therapy (SBRT), who subsequently progressed with imaging-confirmed local tumor progression, and were re-irradiated with a salvage second SBRT course to the same level. Methods and Materials: From a prospective database, 56 metastatic spinal segments in 40 patients were identified as having been irradiated with a salvage second SBRT course to the same level. In addition, 24 of 56 (42.9%) segments had initially been irradiated with conventional external beam radiation therapy before the first course of SBRT. Local control (LC) was defined as no progression on magnetic resonance imaging at the treated segment, and calculated according to the competing risk model. Overall survival (OS) was evaluated for each patient treated by use of the Kaplan-Meier method. Results: The median salvage second SBRT total dose and number of fractions was 30 Gy in 4 fractions (range, 20-35 Gy in 2-5 fractions), and for the first course of SBRT was 24 Gy in 2 fractions (range, 20-35 Gy in 1-5 fractions). The median follow-up time after salvage second SBRT was 6.8 months (range, 0.9-39 months), the median OS was 10.0 months, and the 1-year OS rate was 48%. A longer time interval between the first and second SBRT courses predicted for better OS (P=.02). The crude LC was 77% (43/56), the 1-year LC rate was 81%, and the median time to local failure was 3.0 months (range, 2.7-16.7 months). Of the 13 local failures, 85% (11/13) and 46% (6/13) showed progression within the epidural space and paraspinal soft tissues, respectively. Absence of baseline paraspinal disease predicted for better LC (P<.01). No radiation-induced vertebral compression fractures or cases of myelopathy were observed. Conclusion: A second course of spine SBRT, most often with 30 Gy in 4 fractions, for spinal metastases that failed initial SBRT is a feasible and efficacious salvage treatment option. [ABSTRACT FROM AUTHOR]

Brain metastases (BM) are perceived as a rare complication of prostate cancer associated with poor outcome. Due to limited published data, we conducted a literature review regarding incidence, clinical characteristics, treatment options, and outcomes of patients with prostate cancer BM. A literature analysis of the PubMed, MEDLINE, and EMBASE databases was performed for full-text published articles on patients diagnosed with BM from prostate cancer. Eligible studies included four or more patients. Twenty-seven publications were selected and analyzed. The sources of published patient cohorts were retrospective chart reviews, administrative healthcare databases, autopsy records, and case series. BM are rare, with an incidence of 1.14% across publications that mainly focus on intraparenchymal metastases. Synchronous visceral metastasis and rare histological prostate cancer subtypes are associated with an increased rate of BM. Many patients do not receive brain metastasis-directed local therapy and the median survival after BM diagnosis is poor, notably in patients with multiple BM, dural-based metastases, or leptomeningeal dissemination. Overall, prostate cancer BM are rare and associated with poor prognosis. Future research is needed to study the impact of novel prostate cancer therapeutics on BM incidence, to identify patients at risk of BM, and to characterize molecular treatment targets. [ABSTRACT FROM AUTHOR]

• PSA kinetics and biochemical failure were similar with two-fractions of SABR or HDR. • Quality of life, acute and late toxicities were no different in the two cohorts. • These data support the design of RCTs comparing these treatment approaches. Contemporary radiotherapy for localized prostate cancer (PCa) is deliverable via stereotactic ablative radiotherapy (SABR) and high dose rate (HDR) brachytherapy. Here we report on a parallel cohort analysis of two prospective, phase II clinical trials of two-fraction prostate SABR versus two-fraction HDR monotherapy. Enrolled patients had histologically-confirmed PCa (clinical stage T1c-T2b; grade group 1, 2, or 3; and PSA < 20 ng/mL). SABR and HDR doses were 26 Gy and 27 Gy in 2 weekly fractions, respectively. Patient-level data from each cohort was analysed to assess prostate specific antigen (PSA) response kinetics, biochemical failure, toxicity, and quality of life (QOL). Thirty patients receiving SABR and 83 receiving HDR were included. Fifty percent and 30% of patients had unfavourable-intermediate risk disease, respectively. SABR patients had higher mean baseline PSA (8.7 versus 6.8 ng/mL, p = 0.016). Median follow-up was 72.7 and 65.3 months, respectively. Mean dose delivered (D mean) was 26.6–26.8 Gy for SABR versus 35.5–45.5 Gy for HDR. Both cohorts achieved a median nadir PSA of 0.16 ng/mL at a median of 57 months post-treatment. Cumulative biochemical failure probability (±SE) at 72 months was 3.5% (±3.5%) for SABR versus 12.8% (±4.8%) for HDR (p = 0.19). Low rates of CTCAE grade ≥2 toxicity were observed in both cohorts. No differences in EPIC scores over time were observed between cohorts. Two-fraction SABR yields similar rates of biochemical failure, acute and late toxicities, and QOL as two-faction HDR brachytherapy. These data support the design of a randomized controlled trial comparing these treatments. [ABSTRACT FROM AUTHOR]

Purpose: Despite the increasing use of stereotactic body radiation therapy for non-spine bone metastases (NSBM), there is no established standard for target delineation. The objective of this study was to provide consensus recommendations on clinical target volume (CTV) delineation based on international expert contours.Methods and Materials: Eleven cases of NSBM were contoured by 9 international radiation oncologists. For each case, the gross tumor volume was provided on the simulation computed tomography scans with accompanying magnetic resonance imaging. Participants contoured the CTV and completed a clinical survey. Agreement between CTV contours were analyzed with simultaneous truth and performance level estimation using the kappa coefficient and the Dice similarity coefficient (DSC) and summarized to establish contouring recommendations. A direction-dependent analysis was applied to the consensus contours to quantify margins.Results: All CTV contours were completed. Six participants used a single-dose level, whereas 3 used a 2-dose level simultaneous integrated boost (SIB) technique. For the SIB cases, the largest volume receiving a stereotactic body radiation therapy (SBRT) dose was used for contour analysis. There was substantial agreement between contours across cases with a mean kappa of 0.72 (mean sensitivity 0.85, mean specificity 0.97). The mean DSC value was 0.77 (range, 0.67-0.87). Consensus CTV contouring recommendations were (1) an intraosseous CTV margin of 5 to 10 mm should be strongly considered within contiguous bone; (2) an extraosseous margin of 5 to 10 mm should be strongly considered where there is soft tissue disease or cortical bone disruption; (3) CTVs should be manually cropped to respect anatomic barriers to spread (eg, peritoneal cavity, pleura, uninvolved joint space and cortical bone).Conclusions: CTV contouring recommendations for NSBM-SBRT were established based on analysis of international expert consensus contours with a high level of agreement. These principles may provide guidance to treating physicians and inform future study until prospective clinical data can provide further refinement. [ABSTRACT FROM AUTHOR]

Purpose: Multileaf collimator (MLC) linear accelerator (Linac)-based hypofractionated stereotactic radiation therapy (HSRT) is increasingly used not only for large brain metastases or those adjacent to critical structures but also for those metastases that would otherwise be considered for single-fraction radiosurgery (SRS). However, data on outcomes in general are limited, and there is a lack of understanding regarding optimal dosing. Our aim was to report mature image-based outcomes for MLC-Linac HSRT with a focus on clinical and dosimetric factors associated with local failure (LF).Methods and Materials: A total of 220 patients with 334 brain metastases treated with HSRT were identified. All patients were treated using a 5-fraction daily regimen and were followed with clinical evaluation and volumetric magnetic resonance imaging every 2 to 3 months. Overall survival and progression-free survival were calculated using the Kaplan-Meier method, with LF determined using Fine and Gray's competing risk method. Predictive factors were identified using Cox regression multivariate analysis.Results: Median follow-up was 10.8 months. Median size of treated metastasis was 1.9 cm; 60% of metastases were <2 cm in size. The median total dose was 30 Gy in 5 fractions; 36% of the cohort received <30 Gy. The median time to LF and 12-month cumulative incidence of LF was 8.5 months and 23.8%, respectively. Median time to death and 12-month overall survival rates were 11.8 months and 48.2%, respectively. Fifty-two metastases (15.6%) had an adverse radiation effect, of which 32 (9.5%) were symptomatic necrosis. Multivariable analysis identified worse LF in patients who received a total dose of <30 Gy (hazard ratio, 1.62; P = .03), with LF at 6 and 12 months of 13% and 33% for patients treated with <30 Gy versus 5% and 19% for patients treated with >30 Gy. Exploratory analysis demonstrated a dose-response effect observed in all histologic types, including among breast cancer subtypes.Conclusion: Optimal local control is achieved with HSRT of ≥30 Gy in 5 daily fractions, independent of tumor volume and histology, with an acceptable risk of radiation necrosis. [ABSTRACT FROM AUTHOR]

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 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 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. 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. [ABSTRACT FROM AUTHOR]

• Apparent diffusion coefficient (ADC) from MR-Linac in brain was validated. • ADC from MR-Linac and diagnostic scanner similar in tumours, white/grey matter. • Repeatability of MR-Linac ADC is similar to that of diagnostic scanners. • Daily ADC changes in high-grade gliomas are detectable with MR-Linac. MRI linear accelerators (MR-Linacs) may allow treatment adaptation to be guided by quantitative MRI including diffusion-weighted imaging (DWI). The aim of this study was to evaluate the accuracy and precision of apparent diffusion coefficient (ADC) measurements from DWI on a 1.5 T MR-Linac in patients with central nervous system (CNS) tumours through comparison with a diagnostic scanner. CNS patients were treated using a 1.5 T Elekta Unity MR-Linac. DWI was acquired during MR-Linac treatment and on a Philips Ingenia 1.5 T. The agreement between the two scanners on median ADC over the gross tumour/clinical target volumes (GTV/CTV) and in brain regions (white/grey matter, cerebrospinal fluid (CSF)) was computed. Repeated scans were used to estimate ADC repeatability. Daily changes in ADC over the GTV of high-grade gliomas were characterized from MR-Linac scans. DWI from 59 patients was analyzed. MR-Linac ADC measurements showed a small bias relative to Ingenia measurements in white matter, grey matter, GTV, and CTV (bias: –0.05 ± 0.03, –0.08 ± 0.05, –0.1 ± 0.1, –0.08 ± 0.07 μm2/ms). ADC differed substantially in CSF (bias: –0.5 ± 0.3 μm2/ms). The repeatability of MR-Linac ADC over white/grey matter was similar to previous reports (coefficients of variation for median ADC: 1.4%/1.8%). MR-Linac ADC changes in the GTV were detectable. It is possible to obtain ADC measurements in the brain on a 1.5 T MR-Linac that are comparable to those of diagnostic-quality scanners. This technical validation study adds to the foundation for future studies that will correlate brain tumour ADC with clinical outcomes. [ABSTRACT FROM AUTHOR]

• CEST MRI is feasible on a 1.5 tesla MR-Linac for imaging CNS tumours. • Differences were found in CEST signals between tumour and white matter. • Detectable signal changes between treatment fractions were observed. • Differences in asymmetry were found between high- and low-grade tumours. To describe the implementation and initial results of using Chemical Exchange Saturation Transfer (CEST) for monitoring patients with central nervous system (CNS) tumours treated using a 1.5 tesla MR-guided radiotherapy system. CNS patients were treated with up to 30 fractions (total dose up to 60 Gy) using a 1.5 T Elekta Unity MR-Linac. CEST scans were obtained in 54 subjects at one or more time points during treatment. CEST metrics, including the amide magnetization transfer ratio (MTR Amide), nuclear Overhauser effect (NOE) MTR (MTR NOE) and asymmetry, were quantified in phantoms and CNS patients. The signal was investigated between tumour and white matter, across time, and across disease categories including high- and low-grade tumours. The gross tumour volume (GTV) exhibited lower MTR Amide and MTR NOE and higher asymmetry compared to contralateral normal appearing white matter. Signal changes in the GTV during fractionated radiotherapy were observed. There were differences between high- and low-grade tumours, with higher CEST asymmetry associated with higher grade disease. CEST MRI using a 1.5 T MR-Linac was demonstrated to be feasible for in vivo imaging of CNS tumours. CEST images showed tumour/white-matter contrast, temporal CEST signal changes, and associations with tumour grade. These results show promise for the eventual goal of using metabolic imaging to inform the design of adaptive radiotherapy protocols. [ABSTRACT FROM AUTHOR]

Background: Clinical target volume (CTV) contouring guidelines are frequently developed through studies in which experts contour the CTV for a representative set of cases for a given treatment site and the consensus CTVs are analyzed to generate margin recommendations. Measures of interobserver variability are used to quantify agreement between experts. In cases where an isotropic margin is not appropriate, however, there is no standard method to compute margins in specified directions that represent possible routes of tumor spread. Moreover, interobserver variability metrics are often measures of volume overlap that do not account for the dependence of disagreement on direction. To aid in the development of consensus contouring guidelines, this study demonstrates a novel method of quantifying CTV margins and interobserver variability in clinician-specified directions.Methods: The proposed algorithm was applied to 11 cases of non-spine bone metastases to compute the consensus CTV margin in each direction of intraosseous and extraosseous disease. The median over all cases for each route of spread yielded the recommended margins. The disagreement between experts on the CTV margin was quantified by computing the median of the coefficients of variation for intraosseous and extraosseous margins.Results: The recommended intraosseous and extraosseous margins were 7.0 mm and 8.0 mm, respectively. The median coefficient of variation quantifying the margin disagreement between experts was 0.59 and 0.48 for intraosseous and extraosseous disease.Conclusions: The proposed algorithm permits the generation of margin recommendations in relation to adjacent anatomy and quantifies interobserver variability in specified directions. This method can be applied to future consensus CTV contouring studies. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic resonance image (MRI) guided radiation therapy has the potential to improve outcomes for glioblastoma by adapting to tumor changes during radiation therapy. This study quantifies interfraction dynamics (tumor size, position, and geometry) based on sequential magnetic resonance imaging scans obtained during standard 6-week chemoradiation.Methods and Materials: Sixty-one patients were prospectively imaged with gadolinium-enhanced T1 (T1c) and T2/FLAIR axial sequences at planning (Fx0), fraction 10 (Fx10), fraction 20 (Fx20), and 1 month after the final fraction of chemoradiation therapy (P1M). Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured at all time points. Target dynamics were quantified by absolute volume (V), volume relative to Fx0 (Vrel), and the migration distance (dmigrate; the linear displacement of the GTV or CTV relative to Fx0). Temporal changes were assessed using a linear mixed-effects model.Results: Median volumes at Fx0, Fx10, Fx20, and P1M for the GTV were 18.4 cm3 (range, 1.1-110.5 cm3), 14.7 cm3 (range, 0.9-115.1 cm3), 13.7 cm3 (range, 0.6-174.2 cm3), and 13.0 cm3 (range, 0.9-76.3 cm3), respectively, with corresponding median Vrel of 0.88 at Fx10, 0.77 at Fx20, and 0.71 at P1M relative to Fx0 (P < .001 for all). The GTV (CTV) migration distances were greater than 5 mm in 46% (54%) of patients at Fx10, 50% (58%) of patients at Fx20, and 52% (57%) of patients at P1M. Dynamic tumor morphologic changes were observed, with 40% of patients exhibiting a decreased GTV (Vrel ≤1) with a dmigrate >5 mm during chemoradiation therapy.Conclusions: Clinically meaningful tumor dynamics were observed during chemoradiation therapy for glioblastoma, supporting evaluation of daily MRI guided radiation therapy and treatment plan adaptation. [ABSTRACT FROM AUTHOR]

• High dose-rate brachytherapy (HDR) has low rate of late urinary or bowel toxicity. • Grade 3 urinary toxicity was rare and only seen after single fraction. • No detriment in urinary quality of life after the first year with two fraction HDR. • Single fraction HDR resulted in decreased urinary quality of life at 4 and 5 years. Long-term toxicity of high dose-rate brachytherapy as monotherapy for prostate cancer is not well defined. We report late toxicity and health related quality of life (HRQOL) changes from a randomized phase II clinical trial of two different fractionation schemes. Eligible patients had NCCN low or intermediate risk prostate cancer. 170 patients were randomized to receive either a single 19 Gy or two-fractions of 13.5 Gy one week apart. Toxicity was measured using Common Terminology for Adverse Events (CTCAE) v4.0, and HRQOL was measured using the Expanded Prostate Index Composite (EPIC). Median follow-up was 63 months. The 5-year cumulative incidence of Grade 2 or higher genitourinary (GU) and gastrointestinal (GI) toxicity was 62% and 12% in the single-fraction arm, and 47% and 9% in the two-fraction arm, respectively. Grade 3 GU toxicity was only seen in the single fraction arm with a cumulative incidence of 2%. The 5-year prevalence of Grade 2 GU toxicity was 29% and 21%, in the single- and two-fraction arms, respectively, with Grade 2 GI toxicity of 1% and 2%. Beyond the first year, no significant differences in mean urinary HRQOL were seen compared to baseline in the two-fraction arm, in contrast to the single-fraction arm where a decline in urinary HRQOL was seen at 4 and 5 years. Sexual HRQOL was significantly reduced in both treatment arms at all timepoints, with no changes in the bowel domain. HDR monotherapy is well tolerated with minimal impact on HRQOL. [ABSTRACT FROM AUTHOR]

• Simplified IVIM metrics from MRIs taken during chemoradiation have prognostic value. • Nonenhancing T2-FLAIR regions have important prognostic value. Prediction of early progression in glioblastoma may provide an opportunity to personalize treatment. Simplified intravoxel incoherent motion (IVIM) MRI offers quantitative estimates of diffusion and perfusion metrics. We investigated whether these metrics, during chemoradiation, could predict treatment outcome. 38 patients with newly diagnosed IDH-wildtype glioblastoma undergoing 6-week/30-fraction chemoradiation had standardized post-operative MRIs at baseline (radiation planning), and at the 10th and 20th fractions. Non-overlapping T1-enhancing (T1C) and non-enhancing T2-FLAIR hyperintense regions were independently segmented. Apparent diffusion coefficient (ADC T1C , ADC T2-FLAIR) and perfusion fraction (f T1C , f T2-FLAIR) maps were generated with simplified IVIM modelling. Parameters associated with progression before or after 6.9 months (early vs late progression, respectively), overall survival (OS) and progression-free survival (PFS) were investigated. Higher ADC T2-FLAIR at baseline [Odds Ratio (OR) = 1.06, 95% CI 1.01–1.15, p = 0.025], lower f T2-FLAIR at fraction 10 (OR = 2.11, 95% CI 1.04–4.27, p = 0.018), and lack of increase in ADC T2-FLAIR at fraction 20 compared to baseline (OR = 1.12, 95% CI 1.02–1.22, p = 0.02) were associated with early progression. Combining ADC T2-FLAIR at baseline, f T2-FLAIR at fraction 10, ECOG and MGMT promoter methylation status significantly improved AUC to 90.3% compared to a model with only ECOG and MGMT promoter methylation status (p = 0.001). Using multivariable analysis, neither IVIM metrics were associated with OS but higher f T2-FLAIR at fraction 10 (HR = 0.72, 95% CI 0.56–0.95, p = 0.018) was associated with longer PFS. ADC T2-FLAIR at baseline, its lack of increase from baseline to fraction 20, or f T2-FLAIR at fraction 10 significantly predicted early progression. f T2-FLAIR at fraction 10 was associated with PFS. [ABSTRACT FROM AUTHOR]

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

• Single fraction high dose-rate brachytherapy has high local recurrence rate. • Dose escalation with an MR-guided boost to the dominant lesion does not improve outcome. • Single fraction protocols should not be used. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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 D 90 , D mean , V 150 , and V 200 to the prostate and DIL were reported. For urethra and rectum, D 10 and V 80 were reported. 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. 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 D 90 and D mean. 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. [ABSTRACT FROM AUTHOR]

• Short-term ADT increased BFFS in UIR patients treated with HDT-BT boost. • CRFS and MFS were not impacted by ADT use. • UIR patients treated with ADT had similar BFFS to favourable intermediate risk (FIR). 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. 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. 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. Short-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning–based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated. 41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning–based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V 150% isodose volume between either the PIPA—or conventional—and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30. 21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D 90% , V 100% , rectum V 100 , or rectum D 1cc between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05). A machine learning–based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners. [ABSTRACT FROM AUTHOR]

• HDR monotherapy as 13.5 Gy × 2 is highly effective for low and intermediate risk prostate cancer. • Single fraction HDR monotherapy has high local failure rate and should not be used. • HDR monotherapy has low toxicity. High dose-rate (HDR) brachytherapy as monotherapy is a treatment option for localized prostate cancer, but optimal dose and fractionation is unknown. We report efficacy results of a randomized phase II trial of HDR monotherapy delivered as either one or two fractions. Eligible patients had low or intermediate risk prostate cancer, prostate volume <60 cc, and no androgen deprivation use. 170 patients were randomized to receive HDR as either a single fraction of 19 Gy or as two fractions of 13.5 Gy one week apart. Median age was 65 years, median PSA was 6.33 ng/ml, and Grade Group 1, 2 and 3 was present in 28%, 60%, and 12%, respectively. There was no difference in baseline factors between arms and 19%, 51% and 30% had low risk, favourable intermediate and unfavourable intermediate risk disease, respectively. The Phoenix definition was used to define biochemical failure, all local failures were confirmed by biopsy and toxicity was assessed using CTCAE v.4. Median follow-up was 60 months. PSA decreased more quickly in the 2-fraction arm (p = 0.009). Median PSA at 5-years was 0.65 ng/ml in the single fraction and 0.16 ng/ml in the 2-fraction arm. The 5-year biochemical disease-free survival and cumulative incidence of local failure was 73.5% and 29% in the single fraction arm and 95% (p = 0.001) and 3% (p < 0.001) in the 2-fraction arm, respectively. Recurrence was not associated with initial stage, grade group, or risk group. Grade 2 late rectal toxicity occurred in 1% while the incidence of grade 2 and 3 urinary toxicity was 45% and 1%, respectively, with no difference between arms. HDR monotherapy delivered as two fraction of 13.5 Gy is well tolerated with a high cancer control rate at 5 years. Single fraction monotherapy is inferior and should not be used. [ABSTRACT FROM AUTHOR]

Purpose: Limited data exist quantifying the risk of adverse radiation effect (ARE) specific to hypofractionated stereotactic radiosurgery (HSRS). We present our analyses of the risk of ARE after 5 daily fractions of HSRS to surgical cavities and intact metastases.Methods and Materials: One hundred and eighty-seven consecutively treated patients with 118 surgical cavities and 132 intact metastases were retrospectively reviewed. All patients were treated with 5 daily fractions with a 2 mm planning target volume applied. Clinical and dosimetric variables were assessed to identify predictors of ARE.Results: The median total prescribed dose was 30 Gy (range, 20-35 Gy) and median follow-up was 12 months. One hundred forty-four patients (77%) received treatment to a single target. Median planning target volumes for resection cavity and intact metastases were 24.9 cm3 and 7.7 cm3, respectively. ARE and symptomatic ARE were observed 21.2% and 10.8% of targets, respectively, and the median time to ARE was 8 months. Time to ARE was <6 months for 38%, 6 to 12 months for 43%, and >12 months for 19% of targets. Multivariable analysis identified intact metastases versus cavities (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.33-10) as a significant predictor of symptomatic ARE. Specific to cavity HSRS, prior whole brain radiation therapy (OR 7.73; 95% CI, 1.67-35.69) and prior stereotactic radiosurgery (OR 8.66; 95% CI, 1.14-65.7) were significant predictors of symptomatic ARE. For intact metastases, the total brain minus gross tumor volume (GTV) receiving 30 Gy (BMC30) was a significant predictor of symptomatic ARE (OR, 1.21; 95% CI, 1.02-1.43), and a volume-based BMC30 threshold of 10.5 cm3 was significant with an OR of 7.21 (95% CI, 1.31-39.45).Conclusions: The risk of ARE was greater for intact metastases compared with cavities after HSRS. For intact lesions, the BMC30 was predictive for symptomatic necrosis, and a threshold of 10.5 cm3 may guide treatment planning. [ABSTRACT FROM AUTHOR]

• Higher SBRT doses result in better local control for colorectal metastases. • Liver metastases independently have worse local control compared to other sites. • A good proportion of patients did not have a change in systemic therapy after SBRT. To review the clinical outcomes following the use of stereotactic body radiotherapy (SBRT) in patients with metastatic colorectal cancer (mCRC) from a large academic institution. Patients with mCRC treated with extracranial SBRT between 2008 and 2016 were identified from an institutional database. Treatment indications were oligometastases, oligoprogression, and local control of dominant tumors. Endpoints included local progression (LP), overall survival (OS), progression-free survival (PFS), and cumulative incidence of starting or changing systemic therapy (SCST). Univariate and multivariable analyses (MVA) were performed to identify predictive factors. One hundred and sixty-five patients (262 lesions treated) were included. The 2-year cumulative incidence of LP was 23.8%. Lower SBRT doses and tumor location in the liver were significant predictors of LP on MVA. Median OS was 49.3 months, 19.3 months, and 9.0 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. Primary tumor not in situ, smaller tumors, fewer lines of previous systemic therapy, lower CEA, and oligometastases treatment indications were significant predictors of higher OS on MVA. For the entire cohort, median PFS was 9.9 months, while oligometastatic patients had a median PFS of 12.4 months. 2-year cumulative incidence of SCST was 41.7%. Survival outcomes are favorable after SBRT for mCRC patients. A significant proportion of patients did not have a change in systemic therapy after SBRT. Higher doses are required to obtain the best local control. Efforts should be made to better optimize SBRT delivery for liver metastases given their higher local failure rate. [ABSTRACT FROM AUTHOR]

About 20–40% of cancer patients develop brain metastases, causing significant morbidity and mortality. Stereotactic radiation treatment is an established option that delivers high dose radiation to the target while sparing the surrounding normal tissue. However, up to 20% of metastatic brain tumours progress despite stereotactic treatment, and it can take months before it is evident on follow-up imaging. An early predictor of radiation therapy outcome in terms of tumour local failure (LF) is crucial, and can facilitate treatment adjustments or allow for early salvage treatment. In this study, an MR-based radiomics framework was proposed to derive and investigate quantitative MRI (qMRI) biomarkers for the outcome of LF in brain metastasis patients treated with hypo-fractionated stereotactic radiation therapy (SRT). The qMRI biomarkers were constructed through a multi-step feature extraction/reduction/selection framework using the conventional MR imaging data acquired from 100 patients (133 lesions), and were applied in conjunction with machine learning techniques for outcome prediction and risk assessment. The results indicated that the majority of the features in the optimal qMRI biomarkers characterize the heterogeneity in the surrounding regions of tumour including edema and tumour/lesion margins. The optimal qMRI biomarker consisted of five features that predict the outcome of LF with an area under the curve (AUC) of 0.79, and a cross-validated sensitivity and specificity of 81% and 79%, respectively. The Kaplan-Meier analyses showed a statistically significant difference in local control (p-value < 0.0001) and overall survival (p = 0.01). Findings from this study are a step towards using qMRI for early prediction of local failure in brain metastasis patients treated with SRT. This may facilitate early adjustments in treatment, such as surgical resection or salvage radiation, that can potentially improve treatment outcomes. Investigations on larger cohorts of patients are, however, required for further validation of the technique. [ABSTRACT FROM AUTHOR]

• There is no evidence-based data to guide dose constraints in 2-fraction prostate SABR. • We used real-life patient data from 2-fraction prostate SABR trials for this study. • We identified dosimetric parameters associated with late grade ≥ 2 toxicities. • The findings will be useful to guide dose constraints in future 2-fraction prostate SABR. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

[Display omitted] • MR-Linac diffusion MRI (DWI) changes in glioblastoma are prognostic. • DWI changes correlate with survival two to five weeks from radiotherapy start. • DWI changes show greater survival correlation than gross tumour volume changes. Survival in glioblastoma might be extended by escalating the radiotherapy dose to treatment-resistant tumour and adapting to tumour changes. Diffusion-weighted imaging (DWI) on MRI-linear accelerators (MR-Linacs) could be used to identify a dose escalation target, but its prognostic value must be demonstrated. The purpose of this study was to determine whether MR-Linac DWI can assess treatment response in glioblastoma and whether changes in DWI show greater prognostic value than changes in the contrast-enhancing gross tumour volume (GTV). Seventy-five patients with glioblastoma were treated with chemoradiotherapy, of which 32 were treated on a 1.5 T MRI-linear accelerator (MR-Linac). Patients were imaged with simulation MRI scanners (MR-sim) at treatment planning and weeks 2, 4, and 10 after treatment start. Twenty-eight patients had additional MR-Linac DWI sequences. Cox modelling was used to evaluate the correlation of overall and progression-free survival (OS and PFS) with clinical variables and volumetric changes in the GTV and low-ADC regions (ADC < 1.25 µm2/ms within GTV). In total, 479 MR-Linac DWI and 289 MR-sim DWI datasets were analyzed. MR-Linac low-ADC changes between weeks 2 and 5 inclusive were prognostic for OS (hazard ratio lower limits ≥ 1.2, p-values ≤ 0.02). MR-sim low-ADC changes showed greater correlation with OS and PFS than GTV changes (e.g., OS hazard ratio at week 2 was 3.4 (p <0.001) for low-ADC versus 2.0 (p = 0.022) for GTV). MR-Linac DWI can measure low-ADC tumour volumes that correlate with OS and PFS better than contrast-enhancing GTV. Low-ADC regions could serve as dose escalation targets. [ABSTRACT FROM AUTHOR]