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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.

BackgroundPreclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer.Methods and findingsThis prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial.ConclusionsMRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials.Trial registrationclinicaltrials.gov, identifier NCT04431674.

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.

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: 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 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 Surgical devices are commonly used during breast conservative surgery (BCS) to provide better hemostasis. The Harmonic scalpel has recently gained momentum as an effective tool for intraoperative bleeding reduction. This comparative study was designed to determine the efficacy of Harmonic Focus in reducing postoperative complications of BCS after neoadjuvant chemotherapy (CTH) compared to the conventional method using monopolar diathermy. Results A prospective, nonrandomized, comparative study was conducted on patients scheduled to undergo BCS with axillary dissection after neoadjuvant CTH. Patients in the Harmonic Focus group had significantly shorter operative times than the monopolar electrocautery group (101.32 ± 27.3 vs. 139.3 ± 31.9 min, respectively; p < 0.001). Besides, blood loss was significantly lower in the Harmonic Focus group (117.14 ± 35.6 vs. 187 ± 49.8 mL, respectively; p < 0.001). Postoperatively, patients in the Harmonic Focus group had a significantly lower volume of chest wall drain (p < 0.001) and shorter time until drain removal (p < 0.001). Likewise, patients in the Harmonic Focus group had a significantly lower volume of axillary drain and shorter time until drain removal than monopolar electrocautery (p < 0.001). The incidence of postoperative complications was comparable between both groups (p = 0.128). Conclusions This study confirmed the superiority of Harmonic Focus compared to monopolar electrocautery among patients receiving neoadjuvant CTH before BCS.

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 The oncological outcomes of laparoscopic gastrectomy (LG) and open gastrectomy (OG) following neoadjuvant chemotherapy have been investigated in a few studies. Our purpose was to evaluate the oncological outcomes of LG and OG after neoadjuvant chemotherapy in patients with locally advanced gastric cancer (GC) and to determine the advantages, preferences, and ease of use of the two techniques after chemotherapy. Methods We conducted a retrospective chart review of all patients who underwent either OG (n = 43) or LG (n = 41). The neoadjuvant treatment regimen consisted of capecitabine plus oxaliplatin for three cycles, which was then repeated 6 to 12 weeks after the operation for four cycles. Results The hospital stay time and intraoperative blood loss in the LG group were significantly lower than those in the OG group. The mortality rate and the 3-year survival rate for patients in the LG group were comparable to those of patients in the OG group (4.6% vs. 9.7% and 68.3% vs. 58.1%, respectively). Similar trends were observed regarding the 3-year recurrence rate and metastasis. The mean survival time was 52.9 months (95% confidence interval [CI], 44.2–61.6) in the OG group compared with 43.3 (95% CI, 36.6–49.8) in the LG group. Likewise, the mean disease-free survival was 56.1 months (95% CI, 46.36–65.8) in the LG group compared with 50.9 months (95% CI, 44.6–57.2) in the OG group. Conclusion LG is a feasible and safe alternative to OG for patients with locally advanced GC receiving neoadjuvant chemotherapy.

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

Radiation dermatitis is a common adverse effect of radiotherapy (RT) in breast cancer patients. Although radiation dermatitis is reported by either the clinician or the patient, previous studies have shown disagreement between clinician-reported outcomes (CROs) and patient-reported outcomes (PROs). This review evaluated the extent of discordance between CROs and PROs for radiation dermatitis. Studies reporting both clinician and patient-reported outcomes for external beam RT were eligible. Nine studies met the inclusion criteria for the systematic review, while 8 of these studies were eligible for inclusion in a meta-analysis of acute and late skin toxicities. We found an overall agreement between CROs and PROs of acute skin colour change, fibrosis and/or retraction, and moist desquamation (p > 0.005). Reporting of late breast pain, breast edema, skin colour change, telangiectasia, fibrosis and/or retraction and induration/fibrosis alone (p > 0.005) were also in agreement between clinicians and patients. Our meta-analysis revealed a greater reporting of acute breast pain by patients (RR = 0.89, 95% CI 0.87–0.92, p

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.

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: The coronavirus disease 2019 (COVID-19) pandemic has propelled health care workers to the front lines against the pandemic. In addition to anxiety related to infection risks, trainees have the additional burden of learning and career planning while providing care in an uncertain and rapidly changing environment. We conducted a survey to evaluate the practical and psychosocial impact on radiation oncology fellows during the first month of the pandemic. Methods and Materials: A 4-part survey was designed and distributed to the fellows in our program. The survey was designed to evaluate the impact of the pandemic on scope of activity and well-being (“Impact on You”) and to identify key lessons learned and social factors (“About You”) using Likert scales and open-ended response options. The survey included items from the Oldenburg Burnout questionnaire. Results: A total of 17 participants (71%) responded to the survey. Although there was a significant reduction in the mean time spent on in-person clinics (13.5 h/wk [pre-COVID] vs 9.3 h/wk [3 weeks into the COVID emergency response]; P = .002), this was replaced by virtual consults and other COVID-related activities. The proportion of respondents demonstrating features of burnout in the domains of “disengagement” and “exhaustion” was 71% and 64%, respectively. However, there was also evidence of resilience, with 47% respondents “feeling energized.” Top “concerns” and “negative changes” identified related to learning, infection risk and safety, patient care, coping, and concerns about their home country. Top “positive changes” highlighted include work culture, appreciation for leadership caring for the team, the insistence on evidence to guide change, and the implementation of virtual health care. Conclusions: Negative impact needs to be anticipated, acknowledged, and managed. We anticipate understanding the positives that have emerged under these extraordinary circumstances is the “silver lining” of the pandemic, giving us tools and the best leverage to plan for the future.

Abstract Background Emerging techniques such as brain hypo-fractionated radiotherapy (HF-RT) involve complex cases with limited guidelines for plan quality and normal tissue tolerances. The purpose of the present study was to statistically parameterize irradiated volume independently of dose prescription, or margin to determine what spread in achievable irradiated volume one may expect for a given case. Methods We defined EXT as the total tissue within the external contour of the patient (including the target) and we defined BMP as the contour of the brain minus PTV. Irradiated volumes of EXT and BMP at specific doses (i.e. 50, 60%, etc., of the prescribed dose) were extracted from 135 single-target HF-RT clinical cases, each planned with a single-arc, homogeneous (SAHO) approach in which target maximum dose (Dmax) was constrained to 3 targets (N = 10) to investigate the effect of target number. We also examined the effect of shape complexity. A series of best fit curves with confidence and prediction intervals were generated for irradiated volume versus total target volume and the resulting model was subsequently validated on a subsequent set of 23 consecutive prospective cases not originally used in curve-fitting. A subset of 30 HF-RT cases were re-planned with a well-published four-arc, heterogeneous (FAHE) radiosurgery planning approach (Dmax could exceed 130%) to demonstrate how technique affects irradiated volume. Results For SAHO, strong correlation (R2 > 0.98) was found for predicting irradiated volumes. For a given total target volume, irradiated-volume increased by a range of 1.4–2.9× for >3 versus single-targets depending on isodose level. Shape complexity had minor impact on irradiated volume. There was no statistical difference in irradiated volumes between validation and input data (p > 0.2). The FAHE-generated irradiated volumes yielded curves and prediction and confidence bands that agreed well with published data indicating that the proposed approach is feasible for cross-institutional comparisons. Conclusions A description of irradiated volume for linac-based HF-RT is proposed based on population data. We have demonstrated that the proposed approach is feasible for inter and intra-institutional comparisons.

Lactate is now recognized as an important intermediate in brain metabolism, but its role is still under investigation. In this work we mapped the distribution of lactate and bicarbonate produced from intravenously injected 13C-pyruvate over the whole brain using a new imaging method, hyperpolarized 13C MRI (N = 14, ages 23 to 77). Segmenting the 13C-lactate images into brain atlas regions revealed a pattern of lactate that was preserved across individuals. Higher lactate signal was observed in cortical grey matter compared to white matter and was highest in the precuneus, cuneus and lingual gyrus. Bicarbonate signal, indicating flux of [1–13C]pyruvate into the TCA cycle, also displayed consistent spatial distribution. One-way ANOVA to test for significant differences in lactate among atlas regions gave F = 87.6 and p

Brain metastases are the most common intracranial tumors and occur in 20–40% of all cancer patients. Lung cancer, breast cancer, and melanoma are the most frequent primary cancers to develop brain metastases. Treatment options include surgical resection, whole brain radiotherapy, stereotactic radiosurgery, and systemic treatment such as targeted or immune therapy. Anatomical magnetic resonance imaging (MRI) of the tumor (in particular post-Gadolinium T1-weighted and T2-weighted FLAIR) provide information about lesion morphology and structure, and are routinely used in clinical practice for both detection and treatment response evaluation for brain metastases. Advanced MRI biomarkers that characterize the cellular, biophysical, micro-structural and metabolic features of tumors have the potential to improve the management of brain metastases from early detection and diagnosis, to evaluating treatment response. Magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), quantitative magnetization transfer (qMT), diffusion-based tissue microstructure imaging, trans-membrane water exchange mapping, and magnetic susceptibility weighted imaging (SWI) are advanced MRI techniques that will be reviewed in this article as they pertain to brain metastases.

The oligometastatic state is hypothesized to represent an intermediary state of cancer between widely metastatic disease and curable, localized disease. Advancements in radiotherapy have allowed for delivery of high precision, dose escalated treatment known as stereotactic body radiotherapy (SBRT) to targets throughout the body with excellent rates of local control. Recently, the first phase II randomized trial comparing conventional radiotherapy to comprehensive SBRT of oligometastatic disease demonstrated an overall survival and progression free survival advantage. The spine is a common site of metastasis, and a complex site for SBRT given the adjacent spinal cord and the tumor embedded within the bone tissue putting the patient at risk of fracture. Although there are expert spine SBRT guidelines for practice, there are as yet no reported randomized trials that proves superiority as compared to conventional radiation. The use of SBRT in patients with oligometastatic disease and spinal metastases is the focus of this review.

Purpose: Radiation therapy is the standard treatment for symptomatic bone metastases. Several randomized control trials and meta-analyses have concluded a similar efficacy in pain relief when comparing single versus multiple fraction regimes. However, there continues to be reluctance to conform to published guidelines that recommend a single treatment for the palliation of painful bone metastases. The purpose of this literature review is to summarize international patterns of practice, and to determine if guidelines recommending single fraction treatment have been implemented in clinical care. Methods: A literature search was conducted in Ovid Medline, Embase, and Cochrane Central. Search words included, ‘bone metastases’, ‘radiation therapy’, ‘radiotherapy’, ‘patterns of practice’, and ‘dose fractionation’. Both prospective and retrospective studies that investigated the prescription of radiotherapy to bone metastases using actual patient databases were included. Articles were excluded if they investigated hypothetical scenarios. Results: Six hundred and thirteen results were generated from the literature search. Twenty-six articles met the inclusion criteria. Of these, 11 were Canadian, 8 were European, 6 were American, and 1 was Australian. The use of single fraction radiotherapy (SFRT) ranged from 3% to 75%, but was generally lower in American studies. Choice of fractionation depended on a variety of factors, including patient age, prognosis, site of irradiation, and physician experience. Conclusion: Despite the publication of robust randomized control trials, meta-analyses, and clinical practice guidelines recommending the use of a single treatment to palliate uncomplicated bone metastasis, SFRT is internationally underutilized.

Purpose: Pain flare is a temporary increase in pain and is a potential side effect of radiotherapy treatment. However, its incidence has been reported only in recent studies, and with great variability. A few studies have reported on the use of dexamethasone as a prophylactic agent in the prevention of pain flare. The objective of this study is to present a review of the available literature regarding the incidence of pain flare and use of dexamethasone as a preventative measure. Methods: A literature search was conducted in PubMed using subject keywords including: “radiation therapy”, “stereotactic radiation therapy”, “bone metastases”, “pain flare”, and “dexamethasone”. The search was limited to English only but not restricted to any time period. Additionally, a search was also conducted in the American Society for Therapeutic Radiology and Oncology (ASTRO) 2014 book of published abstracts. Inclusion criteria were primary studies published with full text and/or abstracts only. Letters to the editor were excluded. Results: A total of 11 studies were selected, two of which were abstracts published by ASTRO in 2014. Seven articles investigated pain flare and/or dexamethasone use for conventional external beam radiation therapy (EBRT) while the remaining four investigated stereotactic body radiation therapy (SBRT). Pain flare incidence ranged from 2 to 44% for EBRT and 10 to 68% in SBRT. The use of dexamethasone also showed to be effective in both the prophylaxis and treatment of pain flare. Conclusions: Pain flare has been established as an acute toxicity of both EBRT and SBRT, although its incidence is widely variable due to differences in data collection. The use of dexamethasone in the prophylaxis of pain flare is efficacious. Future studies are required in order to both optimize the reporting of pain and the dexamethasone regimens in the prevention of pain flare.

TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18-0.37], p = 0.0001) or for pT1 tumours alone (OR = 0.47 [0.28-0.79], p = 0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23-1.36] (p = 0.12) and OR = 0.99 [0.37-2.7] (p = 0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.

BackgroundWe have previously shown that angiopoietin-like 4 (angptl4) mRNA, a hypoxia-inducible gene, is highly expressed in clear cell renal-cell carcinoma (ccRCC), the most common subtype of RCC for which no specific marker is available. We here investigated whether angptl4 mRNA 1) could be a useful diagnostic and/or prognostic marker of ccRCC in a large and comprehensive retrospective series, 2) induction is dependent on the VHL status of tumors.Methodology/principal findingsUsing in situ hybridization, we report that angptl4 mRNA is expressed in 100% of both sporadic (n = 102) and inherited (n = 6) primary ccRCCs, without any statistical association with nuclear grade (p = 0.39), tumor size (p = 0.09), stage grouping (p = 0.17), progression-free survival (p = 0.94), and overall survival (p = 0.80). Angptl4 mRNA was also expressed in 26 (87%) of 30 secondary ccRCCs but neither in any other secondary RCCs (n = 7). In contrast, angptl4 mRNA was neither expressed in 94% non-ccRCC renal tumors (papillary RCCs (n = 46), chromophobe RCCs (n = 28), and oncocytomas (n = 9)), nor in non-renal clear cell carcinomas (n = 39). Angptl4 expression was also examined in tumors associated (n = 23) or not associated (n = 66) with VHL disease. 40 (98%) hemangioblastomas expressed angptl4 whereas all pheochromocytomas (n = 23) and pancreatic tumors (n = 25) were angptl4-negative, whatever their VHL status.Conclusions/significanceAngptl4 mRNA expression was highly associated with ccRCC (p = 1.5 10(-49), Chi square test) allowing to define its expression as a diagnosis marker for primary ccRCC. Moreover, angptl4 mRNA allows to discriminate the renal origin of metastases of clear-cell carcinomas arising from various organs. Finally, inactivation of VHL gene is neither necessary nor sufficient for angptl4 mRNA induction.

BackgroundIn breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown.Methods and findingsIn this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status.ConclusionsThis study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.