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Objectives: We tested the feasibility and efficacy of a brief mindfulness-based intervention (bMBI) for adult brain tumor (BT) survivors experiencing elevated depressive symptoms. Specifically, we examined whether there are improvements in mental health symptoms (i.e. depressive symptoms, quality of life (QOL), mental wellbeing, perceived stress) among participants at post-intervention.Methods: Nineteen BT survivors participated in a five-session, in-person, group-based bMBI intervention. Data on attendance, depressive symptoms, QOL, mental well-being, and perceived stress were collected at three timepoints. Findings: The preliminary analysis supports that this bMBI: (a) was efficacious in decreasing depressive symptoms and perceived stress, as well as increasing mental well-being and QOL, and (b) was feasible, with a retention rate greater than 70% and an attendance rate greater than 80% for adult BT survivors.Conclusions: These findings lend support for a feasible and efficacious intervention for adult BT survivors experiencing elevated depressive symptomsImplications: With the paucity of psychosocial interventions targeting adult BT survivorship, future empirically rigorous studies for this population are warranted. The uptake/adoption of this bMBI by psychosocial providers may play an important role in improving the mental health and QOL of adult BT survivors.

Summary: Background: Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for brain metastasis (BM), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. Our aim was to describe the clinical characteristics and outcomes of patients with SCLC and BM in Ontario, Canada. Methods: This population-based, retrospective cohort study included all patients in Ontario, Canada, who were diagnosed with SCLC between April 1, 2010, and March 31, 2018. Data were analysed between June 2, 2022, and December 20, 2023. Patients with second cancer diagnosis were excluded. Patients were identified and data retrieved from the Institute for Clinical Evaluative Sciences (ICES) databases. Kaplan–Meier and multivariable Cox regression analyses were performed to compare OS between patient cohorts stratified by disease stage, BM diagnosis, and intracranial treatment modality. Propensity score-matching based on age, disease stage, time to BM, and receipt of chemotherapy was performed to compare OS between intracranial treatment modalities. Findings: 8705 patients were included (male: 4433, female: 4272). Median age at diagnosis was 68 years (interquartile range, IQR, 61–75). Median OS of all patients was 7.46 months (95% confidence interval, CI, 7.23–7.69). 32% (n = 2686) of patients developed BM (synchronous, 43.7%; asynchronous, 56.3%) with median OS of 9.76 months (95% CI, 9.36–10.22). 102 (4%), 1654 (62%), and 930 (35%) patients received stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), or no treatment, respectively, for their BM in the first-line setting or after prophylactic cranial irradiation (PCI). In propensity score-matched analyses, OS from time of BM diagnosis was non-inferior between SRS- and WBRT-treated cohorts among patients who did not receive PCI (hazard ratio, HR, 0.68, 95% CI, 0.44–1.06, p = 0.091, n = 86) and in favour of SRS for those who received PCI prior to BM development (HR, 0.47, 95% CI, 0.31–0.72, p = 0.0042, n = 112). Interpretation: OS for patients with SCLC remains poor, and many patients present with BM. With careful selection, patients with SCLC and BM may benefit from SRS treatment. Future research should incorporate information on burden of intracranial disease and novel immunotherapies. Funding: None.

Intracranial metastatic disease is a serious complication of cancer, treated through surgery, radiation, and targeted therapies. The central role of radiation therapy makes understanding the radioresistance of metastases a priori a key interest for prognostication and therapeutic development. Although historically defined clinic-radiographically according to tumour response, developments in new techniques for delivering radiation treatment and understanding of radioprotective mechanisms led to a need to revisit the definition of radioresistance in the modern era. Factors influencing radioresistance include tumour-related factors (hypoxia, cancer stem cells, tumour kinetics, tumour microenvironment, metabolic alterations, tumour heterogeneity DNA damage repair, non-coding RNA, exosomes, methylomes, and autophagy), host-related factors (volume effect & dose-limiting non-cancerous tissue, pathophysiology, and exosomes), technical factors, and probabilistic factors (cell cycle and random gravity of DNA damage). Influences on radioresistance are introduced and discussed in the context of brain metastases.

Background Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice.Methods Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform’s Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups.Ethics and dissemination Approved by each trial’s ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases.Prospero registration CRD42022330532.

Abstract Preclinical studies have demonstrated focused ultrasound (FUS) stimulated microbubble (MB) rupture leads to the activation of acid sphingomyelinase-ceramide pathway in the endothelial cells. When radiotherapy (RT) is delivered concurrently with FUS-MB, apoptotic pathway leads to increased cell death resulting in potent radiosensitization. Here we report the first human trial of using magnetic resonance imaging (MRI) guided FUS-MB treatment in the treatment of breast malignancies. In the phase 1 prospective interventional study, patients with breast cancer were treated with fractionated RT (5 or 10 fractions) to the disease involving breast or chest wall. FUS-MB treatment was delivered before 1st and 5th fractions of RT (within 1 h). Eight patients with 9 tumours were treated. All 7 evaluable patients with at least 3 months follow-up treated for 8 tumours had a complete response in the treated site. The maximum acute toxicity observed was grade 2 dermatitis in 1 site, and grade 1 in 8 treated sites, at one month post RT, which recovered at 3 months. No RT-related late effect or FUS-MB related toxicity was noted. This study demonstrated safety of combined FUS-MB and RT treatment. Promising response rates suggest potential strong radiosensitization effects of the investigational modality. Trial registration: clinicaltrials.gov, identifier NCT04431674.

Radiotherapy is the dominant treatment modality for painful spine and non-spine bone metastases (NSBM). Historically, this was achieved with conventional low dose external beam radiotherapy, however, stereotactic body radiotherapy (SBRT) is increasingly applied for these indications. Meta-analyses and randomized clinical trials have demonstrated improved pain response and more durable tumor control with SBRT for spine metastases. However, in the setting of NSBM, there is limited evidence supporting global adoption and large scale randomized clinical trials are in need. SBRT is technically demanding requiring careful consideration of organ at risk tolerance, and strict adherence to technical requirements including immobilization, simulation, contouring and image-guidance procedures. Additional considerations include follow up practices after SBRT, with appropriate imaging playing a critical role in response assessment. Finally, there is renewed research into promising new technologies that may further refine the use of SBRT in both spinal and NSBM in the years to come.

Abstract Purpose Integrating magnetic resonance (MR) into radiotherapy planning has several advantages. This report details the clinical implementation of an MR simulation (MR-planning) program for external beam radiotherapy (EBRT) in one of North America's largest radiotherapy programs. Methods and materials An MR radiotherapy planning program was developed and implemented at Sunnybrook Health Sciences Center in 2016 with two dedicated wide-bore MR platforms (1.5 and 3.0 Tesla). Planning MR was sequentially implemented every 3 months for separate treatment sites, including the central nervous system (CNS), gynecologic (GYN), head and neck (HN), genitourinary (GU), gastrointestinal (GI), breast, and brachial plexus. Essential protocols and processes were detailed in this report, including clinical workflow, optimized MR-image acquisition protocols, MR-adapted patient setup, strategies to overcome risks and challenges, and an MR-planning quality assurance program. This study retrospectively reviewed simulation site data for all MR-planning sessions performed for EBRT over the past 5 years. Results From July 2016 to December 2021, 8798 MR-planning sessions were carried out, which corresponds to 25% of all computer tomography (CT) simulations (CT-planning) performed during the same period at our institution. There was a progressive rise from 80 MR-planning sessions in 2016 to 1126 in 2017, 1492 in 2018, 1824 in 2019, 2040 in 2020, and 2236 in 2021. As a result, the relative number of planning MR/CT increased from 3% of all planning sessions in 2016 to 36% in 2021. The most common site of MR-planning was CNS (49%), HN (13%), GYN (12%), GU (12%), and others (8%). Conclusion Detailed clinical processes and protocols of our MR-planning program were presented, which have been improved over more than 5 years of robust experience. Strategies to overcome risks and challenges in the implementation process are highlighted. Our work provides details that can be used by institutions interested in implementing an MR-planning program.

A noticeable proportion of larger brain metastases (BMs) are not locally controlled after stereotactic radiotherapy, and it may take months before local progression is apparent on standard follow-up imaging. This work proposes and investigates new explainable deep-learning models to predict the radiotherapy outcome for BM. A novel self-attention-guided 3D residual network is introduced for predicting the outcome of local failure (LF) after radiotherapy using the baseline treatment-planning MRI. The 3D self-attention modules facilitate capturing long-range intra/inter slice dependencies which are often overlooked by convolution layers. The proposed model was compared to a vanilla 3D residual network and 3D residual network with CBAM attention in terms of performance in outcome prediction. A training recipe was adapted for the outcome prediction models during pretraining and training the down-stream task based on the recently proposed big transfer principles. A novel 3D visualization module was coupled with the model to demonstrate the impact of various intra/peri-lesion regions on volumetric multi-channel MRI upon the network’s prediction. The proposed self-attention-guided 3D residual network outperforms the vanilla residual network and the residual network with CBAM attention in accuracy, F1-score, and AUC. The visualization results show the importance of peri-lesional characteristics on treatment-planning MRI in predicting local outcome after radiotherapy. This study demonstrates the potential of self-attention-guided deep-learning features derived from volumetric MRI in radiotherapy outcome prediction for BM. The insights obtained via the developed visualization module for individual lesions can possibly be applied during radiotherapy planning to decrease the chance of LF.

Chemical exchange saturation transfer (CEST) is a relatively novel magnetic resonance imaging (MRI) technique with an image contrast designed for in vivo measurement of certain endogenous molecules with protons that are exchangeable with water protons, such as amide proton transfer commonly used for neuro-oncology applications. Recent technological advances have made it feasible to implement CEST on clinical grade scanners within practical acquisition times, creating new opportunities to integrate CEST in clinical workflow. In addition, the majority of CEST applications used in neuro-oncology are performed without the use gadolinium-based contrast agents which are another appealing feature of this technique. This review is written for clinicians involved in neuro-oncologic care (nonphysicists) as the target audience explaining what they need to know as CEST makes its way into practice. The purpose of this article is to (1) review the basic physics and technical principles of CEST MRI, and (2) review the practical applications of CEST in neuro-oncology.

Purpose: The goal of this study was to assess the potential real-world effect of the recently reported SC.24 trial on spine stereotactic body radiation therapy (SBRT) utilization. We estimated the proportion of patients treated with conventional radiation therapy (CRT) who would have been eligible for spine SBRT per trial inclusion criteria and analyzed the potential estimated increased costs to our institution. Methods and Materials: This was a retrospective review of patients who received spine CRT at our institution between August and October 2020. Data abstracted included demographics, SC.24 eligibility criteria, provider-reported pain response, and survival. A cost analysis and time survey was performed using institutional and provincial data. Results: Of 73 patients reviewed, 24 patients (33%) were eligible. The most common exclusion factors included irradiation of ≥3 consecutive spinal segments (n = 32, 44%), Eastern Cooperative Oncology Group performance status >2 (n = 17, 23%), and symptomatic spinal cord compression (n = 13, 18%). Of eligible patients, the mean age was 68.92 years, median spinal instability in neoplasia score was 8 (interquartile range, 7-9), and median Eastern Cooperative Oncology Group performance status was 2 (interquartile range, 1-2). The most common primary cancer types among eligible patients were lung (n = 10) and breast (n = 4). The median survival of eligible patients was 10 months (95% confidence interval, 4 months to not reached) with 58% surviving longer than 3 months. Of patients who had subjective pain documented after CRT, 54% had at least some response. The cost of spine SBRT was estimated at CA$4764.80 compared with $3589.10 for CRT, and tasks for spine SBRT took roughly 3 times as long as those for CRT. Conclusions: One-third of patients who received palliative spine CRT met eligibility criteria for SC.24. This possible expanded indication for spine SBRT can have a substantial effect on resource utilization. These data may be useful in guiding resource planning at institutions looking to commence a spine SBRT program.

Objective Patients presenting with neurological deficit secondary to metastatic epidural spinal cord compression (MESCC) are often treated with surgery in combination with high-dose corticosteroids. Despite steroids being commonly used, the evidence regarding the effect of corticosteroids on patient outcomes is limited. The objective of this study was to describe the effect of corticosteroid use on preoperative neurological function in patients with MESCC. Methods Patients who underwent surgery between August 2013 and February 2017 for the treatment of spinal metastases and received steroids to prevent neurologic deficits were included. Data regarding demographics, diagnosis, treatment, neurological function, adverse events, health-related quality of life, and survival were extracted from an international multicenter prospective cohort. Results A total of 30 patients treated surgically and receiving steroids at baseline were identified. Patients had a mean age of 58.2 years (standard deviation, 11.2 years) at time of surgery. Preoperatively, 50% of the patients experienced deterioration of neurological function, while in 30% neurological function was stable and 20% improved in neurological function. Lengthier steroid use did not correlate with improved or stabilized neurological function. Postoperative adverse events were observed in 18 patients (60%). Patients that stabilized or improved neurologically after steroid use showed a trend towards improved survival at 3- and 24-month postsurgery. Conclusion This study described the effect of steroids on preoperative neurological function in patients with MESCC. Stabilization or improvement of preoperative neurological function occurred in 50% of the patients.

Purpose: Magnetic resonance image-guided radiotherapy for intracranial indications is a promising advance; however, uncertainties remain for both target localization after translation-only MR setup and intrafraction motion. This investigation quantified these uncertainties and developed a population-based planning target volume (PTV) model to explore target and organ-at-risk (OAR) volumetric coverage tradeoffs. Methods: Sixty-six patients, 49 with a primary brain tumor and 17 with a post-surgical resection cavity, treated on a 1.5T-based MR-linac across 1329 fractions were included. At each fraction, patients were setup by translation-only fusion of the online T1 MRI to the planning image. Each fusion was independently repeated offline accounting for rotations. The six degree-of-freedom difference between fusions was applied to transform the planning CTV at each fraction (CTVfx). A PTV model parameterized by volumetric CTVfx coverage, proportion of fractions, and proportion of patients was developed. Intrafraction motion was quantified in a 412 fraction subset as the fusion difference between post- and pre-irradiation T1 MRIs. Results: For the left–right/anterior-posterior/superior-inferior axes, mean ± SD of the rotational fusion differences were 0.1 ± 0.8/0.1 ± 0.8/-0.2 ± 0.9°. Covering 98 % of the CTVfx in 95 % of fractions in 95 % of patients required a 3 mm PTV margin. Margin reduction decreased PTV-OAR overlap; for example, the proportion of optic chiasm overlapped by the PTV was reduced up to 23.5 % by margin reduction from 4 mm to 3 mm. Conclusions: An evidence-based PTV model was developed for brain cancer patients treated on the MR-linac. Informed by this model, we have clinically adopted a 3 mm PTV margin for conventionally fractionated intracranial patients.

Abstract Background Brain metastases (BM) in metastatic renal cell carcinoma (mRCC) have been reported to be present in up to 25% of patients diagnosed with mRCC. There is limited published literature evaluating the role of routine intra‐cranial imaging for the screening of asymptomatic BM in mRCC. Aims To evaluate the potential utility of routine intra‐cranial imaging, a retrospective cohort study was conducted to characterize the outcomes of mRCC patients who presented with asymptomatic BM, as compared to symptomatic BM. Methods and Results The Canadian Kidney Cancer Information System (CKCis) database was used to identify mRCC patients diagnosed with BM. This cohort was divided into two groups based on the presence or absence of BM symptoms. Details regarding patient demographics, disease characteristics, systemic treatments, BM characteristics and survival outcomes were extracted. Statistical analysis was through chi‐square tests, analysis of variance, and Kaplan–Meier method to characterize survival outcomes. A p‐value of 1) BM (75%) with no significant differences noted in number of BM or BM‐directed therapy received in symptomatic, as compared to asymptomatic BM patients. Median [95% confidence interval (CI)] overall survival (OS) from mRCC diagnosis was 42 months (95% CI: 32–62) for patients with asymptomatic BM, and 39 months (95% CI: 29–48) with symptomatic BM (p = 0.10). OS from time of BM diagnosis was 28 months (95% CI: 18–42) for the asymptomatic BM group, as compared to 13 months (95% CI: 10–21) in the symptomatic BM group (p = 0.04). Conclusions Given a substantial proportion of patients may present with asymptomatic BM, limiting intra‐cranial imaging to patients with symptomatic BM, may be associated with a missed opportunity for timely diagnosis and treatment. The utility of routine intra‐cranial imaging in patients with renal cell carcinoma, warrants further prospective evaluation.

Abstract This study investigated the effectiveness of pre-treatment quantitative MRI and clinical features along with machine learning techniques to predict local failure in patients with brain metastasis treated with hypo-fractionated stereotactic radiation therapy (SRT). The predictive models were developed using the data from 100 patients (141 lesions) and evaluated on an independent test set with data from 20 patients (30 lesions). Quantitative MRI radiomic features were derived from the treatment-planning contrast-enhanced T1w and T2-FLAIR images. A multi-phase feature reduction and selection procedure was applied to construct an optimal quantitative MRI biomarker for predicting therapy outcome. The performance of standard clinical features in therapy outcome prediction was evaluated using a similar procedure. Survival analyses were conducted to compare the long-term outcome of the two patient cohorts (local control/failure) identified based on prediction at pre-treatment, and standard clinical criteria at last patient follow-up after SRT. The developed quantitative MRI biomarker consists of four features with two features quantifying heterogeneity in the edema region, one feature characterizing intra-tumour heterogeneity, and one feature describing tumour morphology. The predictive models with the radiomic and clinical feature sets yielded an AUC of 0.87 and 0.62, respectively on the independent test set. Incorporating radiomic features into the clinical predictive model improved the AUC of the model by up to 16%, relatively. A statistically significant difference was observed in survival of the two patient cohorts identified at pre-treatment using the radiomics-based predictive model, and at post-treatment using the the RANO-BM criteria. Results of this study revealed a good potential for quantitative MRI radiomic features at pre-treatment in predicting local failure in relatively large brain metastases undergoing SRT, and is a step forward towards a precision oncology paradigm for brain metastasis.

Abstract Background We hypothesized that the total volume of metastases at initial oligometastatic (OM) presentation to stereotactic body radiation therapy (SBRT) is an important prognostic factor that can refine the definition of OM disease. Methods Patients with extracranial oligometastatic cancer (≤5 lesions) treated with SBRT were included in an international multi‐institutional database. Multivariable Cox and competing risks regression models were used to determine the relationship between distant progression‐free survival (DPFS), widespread progression (WSP), and overall survival (OS) with the total planning target volume (PTV) at initial OM presentation to SBRT. All models were adjusted for histology, pre‐SBRT systemic therapy, osseous‐only lesions, and number of metastases. Results In total, 961 patients were included. The median follow‐up was 24.4 months (IQR: 13.8–37.5). Total PTV had a significant effect on DPFS in the first 18 months after SBRT and was most profound in the first 6 months, when each twofold increase in total PTV conferred a 40.6% increased risk of distant progression (p

PurposeThis study reports the workflow and initial clinical experience of high grade glioma (HGG) radiotherapy on the 1.5 T MR-Linac (MRL), with a focus on the temporal variations of the tumor and feasibility of multi-parametric image (mpMRI) acquisition during routine treatment workflow.Materials and methodsTen HGG patients treated with radiation within the first year of the MRL’s clinical operation, between October 2019 and August 2020, were identified from a prospective database. Workflow timings were recorded and online adaptive plans were generated using the Adapt-To-Position (ATP) workflow. Temporal variation within the FLAIR hyperintense region (FHR) was assessed by the relative FHR volumes (n = 281 contours) and migration distances (maximum linear displacement of the volume). Research mpMRIs were acquired on the MRL during radiation and changes in selected functional parameters were investigated within the FHR.ResultsAll patients completed radiotherapy to a median dose of 60 Gy (range, 54-60 Gy) in 30 fractions (range, 30-33), receiving a total of 287 fractions on the MRL. The mean in-room time per fraction with or without post-beam research imaging was 42.9 minutes (range, 25.0–69.0 minutes) and 37.3 minutes (range, 24.0–51.0 minutes), respectively. Three patients (30%) required re-planning between fractions 9 to 12 due to progression of tumor and/or edema identified on daily MRL imaging. At the 10, 20, and 30-day post-first fraction time points 3, 3, and 4 patients, respectively, had a FHR volume that changed by at least 20% relative to the first fraction. Research mpMRIs were successfully acquired on the MRL. The median apparent diffusion coefficient (ADC) within the FHR and the volumes of FLAIR were significantly correlated when data from all patients and time points were pooled (R=0.68, p

Abstract Background Stereotactic body radiotherapy (SBRT) is increasingly used to treat oligometastatic disease (OMD), but the effect of metastasis timing on patient outcomes remains uncertain. Methods An international database of patients with OMD treated with SBRT was assembled with rigorous quality assurance. Early versus late metastases were defined as those diagnosed ≤24 versus >24 months from the primary tumor. Overall survival (OS), progression‐free survival (PFS), and incidences of wide‐spread progression (WSP) were estimated using multivariable Cox proportional hazard models stratified by primary tumor types. Results The database consists of 1033 patients with median follow‐up of 24.1 months (0.3–104.7). Late metastatic presentation (N = 427) was associated with improved OS compared to early metastasis (median survival 53.6 vs. 33.0 months, hazard ratio [HR] 0.59, 95% confidence interval [CI]: 0.47–0.72, p

Abstract 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.

Introduction: Magnetic resonance imaging-linear accelerator radiotherapy is an innovative technology that requires special consideration for secondary electron interactions within the magnetic field, which can alter dose deposition at air–tissue interfaces. As part of ongoing quality assurance and quality improvement of new radiotherapy technologies, the purpose of this study was to evaluate skin dose modelled from the treatment planning systems of a magnetic resonance imaging-linear accelerator and a conventional linear accelerator, and then correlate with in vivo measurements of delivered skin dose from each linear accelerator. Methods: In this prospective cohort study, 37 consecutive glioma patients had treatment planning completed and approved prior to radiotherapy initiation using commercial treatment planning systems: a Monte Carlo-based algorithm for magnetic resonance imaging-linear accelerator or a convolution-based algorithm for conventional linear accelerator. In vivo skin dose was measured using an optically stimulated luminescent dosimeter. Results: Monte Carlo-based magnetic resonance imaging-linear accelerator plans and convolution-based conventional linear accelerator plans had similar dosimetric parameters for target volumes and organs-at-risk. However, magnetic resonance imaging-linear accelerator plans had 1.52 Gy higher mean dose to air cavities ( P

Abstract Several cyclin‐dependent kinase 4/6 (CDK4/6) inhibitors are indicated in the treatment of metastatic hormone receptor‐positive (HR)/ human epidermal growth factor receptor 2 (HER2) negative breast cancer which includes palbociclib, ribociclib and abemaciclib. Pelvic radiation therapy (RT) is often indicated for symptomatic or progressive bone metastasis. There are limited data on concurrent use of CDK4/6 inhibitors with pelvic RT with few retrospective studies in the literature involving a small number of patients. The major side effects of these agents include haematological toxicities, while non‐haematological toxicities are less severe. There are concerns for an increased possibility of synergistic toxicity with concurrent use of CDK4/6 inhibitors with pelvic RT. Here we describe an instance of acute grade 3 gastrointestinal toxicity and discuss the relevant literature. A 77‐year‐old lady treated with palliative conventional RT 30 Gy/ 10 fractions concurrently with palbociclib to left hemipelvis and proximal femur, developed severe pancolitis starting 5 days from last RT. She needed inpatient care for 3 weeks and recovered with mesalamine and supportive care. We also postulate a few strategies that can be adopted in patients receiving palliative RT in such a scenario. The agents should be stopped 1 week before, during and for a time (1 week minimally) after RT. A shorter course of 5 fractions (and ablative RT as indicated) can be considered to minimise treatment gaps. Highly conformal techniques (intensity‐modulated radiotherapy/ volumetric‐modulated arc therapy) can significantly reduce bowel dose and should be considered in patients with pre‐existing GI comorbidities or prior GI toxicity with these agents.

Background and purpose: Post-operative spine stereotactic body radiation therapy (SBRT) represents a significant challenge as there are many restrictions on beam geometry to avoid metal hardware as it surrounds the target volume. In this study, an international multi-institutional end-to-end test using an in-house spine phantom was developed and executed. The aim was to evaluate the impact of titanium spine hardware on planned and delivered dose for post-operative spine SBRT. Materials and methods: Five centers performed simulation, planning and irradiation of the spine phantom, with/without titanium metal hardware (MB/B), following our pre-specified protocol. The doses were calculated using the centers’ treatment planning system (TPS) and measured with radiophotoluminescent glass dosimeters (RPLDs) embedded within each phantom. Results: The dose differences between the RPLD measured and calculated doses in the target region were within ± 5% for both phantoms studied. Differences greater than 5% were observed for the spinal cord and the out-of-the target regions due to steeper dose gradient regions that are created in these plans. Dose measurements within ± 3% were observed between RPLDs that were embedded in MB and B inserts. For the spinal cord and the out-of-target regions surrounded by metal hardware, the dose measured using RPLDs was within 3% different near the titanium screws compared to the dose measured near only the metal rods. Conclusion: We have successfully performed the first multi-institutional end-to-end dose analysis using an in-house phantom built specifically for post-operative spine SBRT. The differences observed between the measured and planned doses in the presence of metal hardware were clinically insignificant.

Abstract Background This study was conducted in order to develop a model for predicting response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) using pretreatment quantitative ultrasound (QUS) radiomics. Methods This was a multicenter study involving four sites across North America, and appropriate approval was obtained from the individual ethics committees. Eighty‐two patients with LABC were included for final analysis. Primary tumors were scanned using a clinical ultrasound system before NAC was started. The tumors were contoured, and radiofrequency data were acquired and processed from whole tumor regions of interest. QUS spectral parameters were derived from the normalized power spectrum, and texture analysis was performed based on six QUS features using a gray level co‐occurrence matrix. Patients were divided into responder or nonresponder classes based on their clinical‐pathological response. Classification analysis was performed using machine learning algorithms, which were trained to optimize classification accuracy. Cross‐validation was performed using a leave‐one‐out cross‐validation method. Results Based on the clinical outcomes of NAC treatment, there were 48 responders and 34 nonresponders. A K‐nearest neighbors (K‐NN) approach resulted in the best classifier performance, with a sensitivity of 91%, a specificity of 83%, and an accuracy of 87%. Conclusion QUS‐based radiomics can predict response to NAC based on pretreatment features with acceptable accuracy.

Background and Purpose: To quantitatively compare the recurrence patterns of glioblastoma (isocitrate dehydrogenase-wild type) versus grade 4 isocitrate dehydrogenase-mutant astrocytoma (wild type isocitrate dehydrogenase and mutant isocitrate dehydrogenase, respectively) following primary chemoradiation. Materials and Methods: A retrospective matched cohort of 22 wild type isocitrate dehydrogenase and 22 mutant isocitrate dehydrogenase patients were matched by sex, extent of resection, and corpus callosum involvement. The recurrent gross tumor volume was compared to the original gross tumor volume and clinical target volume contours from radiotherapy planning. Failure patterns were quantified by the incidence and volume of the recurrent gross tumor volume outside the gross tumor volume and clinical target volume, and positional differences of the recurrent gross tumor volume centroid from the gross tumor volume and clinical target volume. Results: The gross tumor volume was smaller for wild type isocitrate dehydrogenase patients compared to the mutant isocitrate dehydrogenase cohort (mean ± SD: 46.5 ± 26.0 cm 3 vs 72.2 ± 45.4 cm 3 , P = .026). The recurrent gross tumor volume was 10.7 ± 26.9 cm 3 and 46.9 ± 55.0 cm 3 smaller than the gross tumor volume for the same groups ( P = .018). The recurrent gross tumor volume extended outside the gross tumor volume in 22 (100%) and 15 (68%) ( P = .009) of wild type isocitrate dehydrogenase and mutant isocitrate dehydrogenase patients, respectively; however, the volume of recurrent gross tumor volume outside the gross tumor volume was not significantly different (12.4 ± 16.1 cm 3 vs 8.4 ± 14.2 cm 3 , P = .443). The recurrent gross tumor volume centroid was within 5.7 mm of the closest gross tumor volume edge for 21 (95%) and 22 (100%) of wild type isocitrate dehydrogenase and mutant isocitrate dehydrogenase patients, respectively. Conclusion: The recurrent gross tumor volume extended beyond the gross tumor volume less often in mutant isocitrate dehydrogenase patients possibly implying a differential response to chemoradiotherapy and suggesting isocitrate dehydrogenase status might be used to personalize radiotherapy. The results require validation in prospective randomized trials.

Intracranial metastatic disease (IMD) is a prevalent complication of cancer that significantly limits patient survival and quality of life. Over the past half-century, our understanding of the epidemiology and pathogenesis of IMD has improved and enabled the development of surveillance and treatment algorithms based on prognostic factors and tumor biomolecular characteristics. In addition to advances in surgical resection and radiation therapy, the treatment of IMD has evolved to include monoclonal antibodies and small molecule antagonists of tumor-promoting proteins or endogenous immune checkpoint inhibitors. Moreover, improvements in the sensitivity and specificity of imaging as well as the development of new serological assays to detect brain metastases promise to revolutionize IMD diagnosis. In this review, we will explore current treatment principles in patients with IMD, including the emerging role of targeted and immunotherapy in select primary cancers, and discuss potential areas for further investigation.

Purpose: Medical imaging is an indispensable tool in radiotherapy for dose planning, image guidance and treatment monitoring. Cone beam CT (CBCT) is a low dose imaging technique with high spatial resolution capability as a direct by-product of using flat-panel detectors. However, certain issues such as x-ray scatter, beam hardening and other artifacts limit its utility to the verification of patient positioning using image-guided radiotherapy. Methods and Materials: Dual-energy (DE)-CBCT has recently demonstrated promise as an improved tool for tumor visualization in benchtop applications. It has the potential to improve soft-tissue contrast and reduce artifacts caused by beam hardening and metal. In this review, the practical aspects of developing a DE-CBCT based clinical and technical workflow are presented based on existing DE-CBCT literature and concepts adapted from the well-established library of work in DE-CT. Furthermore, the potential applications of DE-CBCT on its future role in radiotherapy are discussed. Results and Conclusions: Based on current literature and an investigation of future applications, there is a clear potential for DE-CBCT technologies to be incorporated into radiotherapy. The applications of DE-CBCT include (but are not limited to): adaptive radiotherapy, brachytherapy, proton therapy, radiomics and theranostics.

Background: Patients with gastrointestinal cancers and brain metastases (BM) represent a unique and heterogeneous population. Our group previously published the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with GI cancers (GI-GPA) (1985–2007, n = 209). The purpose of this study is to update the GI-GPA based on a larger contemporary database. Methods: An IRB-approved consortium database analysis was performed using a multi-institutional (18), multi-national (3) cohort of 792 patients with gastrointestinal (GI) cancers, with newly-diagnosed BM diagnosed between 1/1/2006 and 12/31/2017. Survival was measured from date of first treatment for BM. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. These factors were incorporated into the updated GI-GPA. Results: Median survival (MS) varied widely by primary site and other prognostic factors. Four significant factors (KPS, age, extracranial metastases and number of BM) were used to formulate the updated GI-GPA. Overall MS for this cohort remains poor; 8 months. MS by GPA was 3, 7, 11 and 17 months for GPA 0–1, 1.5–2, 2.5–3.0 and 3.5–4.0, respectively. >30% present in the worst prognostic group (GI-GPA of ≤1.0). Conclusions: Brain metastases are not uncommon in GI cancer patients and MS varies widely among them. This updated GI-GPA index improves our ability to estimate survival for these patients and will be useful for therapy selection, end-of-life decision-making and stratification for future clinical trials. A user-friendly, free, on-line app to calculate the GPA score and estimate survival for an individual patient is available at brainmetgpa.com. Keywords: Gastrointestinal cancers, Brain metastases, Prognosis, End-of-life

Patients undergoing standard chemoradiation post-resection had MRIs at radiation planning and fractions 10 and 20 of chemoradiation. MRIs were 1.5T and 3D T2-FLAIR, pre- and post-contrast 3D T1-weighted (T1) and echo planar DWI with three b-values (0, 500, and 1000s/mm2) were acquired. T2-FLAIR was coregistered to T1C images. Non-overlapping T1 contrast-enhancing (T1C) and nonenhancing T2-FLAIR hyperintense regions were segmented, with necrotic/cystic regions, the surgical cavity, and large vessels excluded. The simplified IVIM model was used to calculate voxelwise diffusion coefficient (D) and perfusion fraction (f) maps; ADC was calculated using the natural logarithm of b = 1000 over b = 0 images. T1C and T2-FLAIR segmentations were brought into this space, and medians calculated. MGMT promoter methylation status (MGMTPMS), age at diagnosis, and Eastern Cooperative Oncology Group (ECOG) performance status were extracted from electronic medical records. The data were presented, analyzed, and described in the article, “Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype Glioblastoma”, published in Radiotherapy and Oncology [1].

Importance: Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors had been recently introduced in clinical practice approved for use in hormone receptor (HR) positive/ human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer. We report the first incidence of radiation recall reaction with the use of abemaciclib. Observations: A 46-year old woman was diagnosed with oligometastatic HR+/HER2- breast cancer (L1 vertebra and right 8th rib). Following mastectomy and sentinel lymph node biopsy, she started letrozole with ovarian suppression. She received loco-regional radiotherapy (RT) to the chest wall and regional lymph nodes to a dose of 50 Gy in 25 fractions using a four-field technique. She was treated with stereotactic body radiotherapy (SBRT) to L1 and rib lesion to a dose of 28 Gy and 24 Gy in 2 fractions, respectively. She had developed grade 2 radiation dermatitis during RT. Subsequently, she was started on palbociclib, which was later switched to abemaciclib 100 mg twice daily due to neutropenia. Three months after switching (14 months after RT), she developed erythema and hyperpigmentation over areas of prior radiation dermatitis. The reaction was grade 2 radiation recall dermatitis (RRD) over the upper back and grade 1 reaction involving axilla, chest wall, and other sites receiving SBRT. The reactions stabilized over the next 3 months with some improvement with the use of emollients and topical steroids. Conclusion and Relevance: This is the first incidence of RRD with the use of a CDK4/6 inhibitor upon switching to abemaciclib (receiving reduced dose) from palbociclib. The RRD possibly had a dose-dependent effect with grade 2 reactions developing over areas receiving higher skin dose.

Purpose: MR-guided Radiation Therapy (MRgRT) allows for high-precision radiotherapy under real-time MR visualization. This enables margin reduction and subsequent dose escalation which may lead to higher tumor control and less toxicity. The Unity MR-linac (Elekta AB, Stockholm, Sweden) integrates a linear accelerator with a 1.5T diagnostic quality MRI and an online adaptive workflow. A prospective international registry was established to facilitate the evidence-based implementation of the Unity MR-linac into clinical practice, to systemically evaluate long-term outcomes, and to aid further technical development of MR-linac-based MRgRT.Methods and Results: In February 2019, the Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac study (MOMENTUM) started within the MR-linac Consortium. The MOMENTUM study is an international academic-industrial partnership between several hospitals and industry partner Elekta. All patients treated on the MR-linac are eligible for inclusion in MOMENTUM. For participants, we collect clinical patient data (e.g., patient, tumor, and treatment characteristics) and technical patient data which is defined as information generated on the MR-linac during treatment. The data are captured, pseudonymized, and stored in an international registry at set time intervals up to two years after treatment. Patients can choose to provide patient-reported outcomes and consent to additional MRI scans acquired on the MR-linac. This registry will serve as a data platform that supports multicenter research investigating the MR-linac. Rules and regulations on data sharing, data access, and intellectual property rights are summarized in an academic-industrial collaboration agreement. Data access rules ensure secure data handling and research integrity for investigators and institutions. Separate data access rules exist for academic and industry partners. This study is registered at ClinicalTrials.gov with ID: NCT04075305 (https://clinicaltrials.gov/ct2/show/NCT04075305).Conclusion: The multi-institutional MOMENTUM study has been set up to collect clinical and technical patient data to advance technical development, and facilitate evidenced-based implementation of MR-linac technology with the ultimate purpose to improve tumor control, survival, and quality of life of patients with cancer.

Abstract Background Different management options exist for patients with brain metastases from non-small cell lung cancer (NSCLC), patients whose treatment with whole brain radiotherapy (WBRT) has become more controversial over the last decade. It is not trivial to find the optimal balance of over- versus undertreatment in these patients. Several recent trials, including the randomized QUARTZ trial now influence the decision to recommend or withhold WBRT for patients with unfavorable prognosis, and similarly, for favorable prognosis patients, the balance between radiosurgery alone or WBRT has become a nuanced decision. Additionally, the availability of intracranially active targeted agent for some subsets of these patients has added another layer of complexity to the decision-making. Methods A multinational consortium of expert radiation oncologists was established with the aim of compiling treatment recommendations for challenging scenarios, in this case the choice between optimal supportive care (SC), WBRT and other types of radiation therapy (RT). We distributed 17 cases to 7 radiation oncologists who were allowed to involve coworkers to provide their treatment recommendations. The cases differed in extra- and intracranial disease extent, histology, age and other prognostic factors. Expert recommendations were tabulated with the aim of providing guidance. Results Regarding willingness to include the 17 patients in the QUARTZ trial, the rates of trial inclusion were low (range 0/7 to 3/7). Experts not recommending trial inclusion provided their treatment recommendations. These suggestions differed widely for most of the patients. It was not uncommon to see 3 or 4 different recommendations. In general, few (0–2) recommended SC. Some kind of local treatment was suggested by the majority of experts for all 17 patients. Commonly, stereotactic single-fraction radiosurgery (SRS) or stereotactic fractionated radiotherapy (SFRT) were recommended by many experts, also for patients with 5–7 lesions. The highest proportion of recommendations towards WBRT in any patient was 3/7. It was also quite common for patients with multiple metastases of varying size that experts suggested combinations of resection, post-operative SRS/SFRT and SRS/SFRT to intact lesions. Despite recommending active treatment, experts were often willing to include the patients in a hypothetical protocol investigating radiotherapy utilization in the last 30 days of life (assessment of factors predicting early death). Conclusions WBRT was infrequently recommended. Even in patients with adverse prognostic features that raised the experts’ awareness of an increased risk for futile treatment near the end of life, SRS/SFRT were more often recommended than optimal supportive care, unless a patient decided to forego active treatment.