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4057 Background: While several clinical scoring systems exist to aid prognostication and patient (pt) selection for clinical trials in oncology, none are standardly used. We compared the ability of four prognostic scores to predict overall survival (OS) in pts with advanced gastric and esophageal (GE) cancer. Methods: Pts with advanced (unresectable or metastatic) GE cancer receiving first-line palliative-intent systemic therapy at the Princess Margaret Cancer Centre from 2007 to 2020 were included. High prognostic risk pts were identified using four scoring systems: Royal Marsden Hospital (RMH), MD Anderson Cancer Centre (MDACC), Gustave Roussy Immune Score (GRIm-S) and MD Anderson Immune Checkpoint Inhibitor (MDA-ICI) score. OS was estimated using the Kaplan-Meier method and compared between risk groups (high vs. not-high) for each scoring system using the log-rank test. Cox proportional hazards models were used to analyze the association between each prognostic score and OS, adjusting for baseline clinical factors. Harrell’s c-index was used to evaluate predictive discrimination of the models. Time-dependent AUCs were used to measure predictive ability for early death (within 90 days). Results: In total, 451 pts with advanced GE cancer were included. The median age was 59 years, 68% were male, 51% had ECOG status 0-1, 63% presented with de novo metastatic disease. The proportion of pts categorized as high risk was: RMH 25% (N=113), MDACC 13% (N=95), GRIm-S 24% (N=109), MDA-ICI 26% (N=117). In all scoring systems, high risk pts had significantly shorter OS (median OS 7.9 versus 12.2 months for RMH high vs. low risk, p

The dorsolateral prefrontal cortex (dlPFC) is primarily involved in higher order executive functions, with there being evidence of lateralization. Brain imaging studies have revealed its link to the generation of skin sympathetic nerve activity (SSNA), which is elevated in states of emotional arousal or anxiety. However, no studies have directly explored dlPFC influences on SSNA. Transcranial alternating current stimulation (−2 to 2 mA, 0.08 Hz, 100 cycles) was applied between the left or right dlPFC and nasion via surface electrodes. Spontaneous bursts of SSNA were recorded from the common peroneal nerve via a tungsten microelectrode in 21 healthy participants. The modulation index was calculated for each stimulation paradigm by constructing cross-correlation histograms between SSNA and the sinusoidal stimulus. Stimulation of the dlPFC caused significant modulation of SSNA, but there was no significant difference in the median modulation index across sides. Stimulation also caused cyclic modulation of skin blood flow and sweat release. We have shown for the first time that stimulation of the dlPFC causes modulation of SSNA, also reflected in the effector-organ responses. This supports a role for the dlPFC in the control of SSNA, which likely contributes to the ability of emotions to bring about cutaneous vasoconstriction and sweat release.

Background Despite the paucity of prospective evidence, stereotactic radiotherapy (SRT) is increasingly being considered in the setting of oligoprogression to delay the need to change systemic therapy. Objective To determine the local control (LC), progression-free survival (PFS), cumulative incidence of changing systemic therapy, and overall survival (OS) after SRT to oligoprogressive metastatic renal cell carcinoma (mRCC) lesions in patients who are on tyrosine kinase inhibitor (TKI) therapy. Design, setting, and participants A prospective multicenter study was performed to evaluate the use of SRT in oligoprogressive mRCC patients. Patients with mRCC who had previous stability or response after ≥3 mo of TKI therapy were eligible if they developed progression of five of fewer metastases. Thirty-seven patients with 57 oligoprogressive tumors were enrolled. Intervention Oligoprogressive tumors were treated with SRT, and the same TKI therapy was continued afterward. Outcome measurements and statistical analysis Competing risk analyses and the Kaplan-Meir methodology were used to report the outcomes of interest. Results and limitations The median duration of TKI therapy prior to study entry was 18.6 mo; 1-yr LC of the irradiated tumors was 93% (95% confidence interval [CI] 71–98%). The median PFS after SRT was 9.3 mo (95% CI 7.5–15.7 mo). The cumulative incidence of changing systemic therapy was 47% (95% CI 32–68%) at 1 yr, with a median time to change in systemic therapy of 12.6 mo (95% CI 9.6–17.4 mo). One-year OS was 92% (95% CI 82–100%). There were no grade 3–5 SRT-related toxicities. Conclusions LC of irradiated oligoprogressive mRCC tumors was high, and the need to change systemic therapy was delayed for a median of >1 yr. Patient summary The use of stereotactic radiotherapy in metastatic kidney cancer patients, who develop growth of a few tumors while on oral targeted therapy, can significantly delay the need to change to the next line of drug therapy.

To determine in a group of patients with progressive metastatic neuroendocrine tumors (PM-NETs) treated with 177Lu-DOTATATE whether a correlation exists between somatostatin receptor (SSTR)-2 expression in various tumors on baseline 68Ga-DOTATATE PET and their response to therapy. A secondary aim was to determine whether an association exists between tumor product of diameter (POD) and PET-derived Krenning score.Patients treated PM-NETs who had SSTR-2 overexpression (SSTR-RADS 5) on screening 68Ga-DOTATATE PET and CT at baseline and 3 months after therapy completion were included. Marker lesions on baseline CT were reassessed on CT after therapy using adapted Southwest Oncology Group solid tumor evaluation criteria. For each lesion, bidimensional diameter on CT and SSTR expression on PET (SSTR-RADS uptake scorePET-derived Krenning score) were recorded. Logistic regression models fitted through generalized estimating equations were used to assess for an association between SSTR expression and response to therapy, or lesion's POD.Forty-one patients with SSTR-RADS 5 PM-NETs treated with 177Lu-DOTATATE were included. There were 135 marker lesions (mean 3.2 lesions/patient) with Krenning score of 4 (n = 74), 3 (n = 44) or 2 (n = 17). There was no association found between SSTR-2 expression, as determined by SSTR-RADS uptake score or PET-derived Krenning score, and POD or response to therapy.In patients with SSTR-RADS 5 PM-NETs treated with 177Lu-DOTATATE, there was similar response to therapy for all lesions with PET-generated Krenning score ≥2. No correlation was found between lesion's POD and level of tracer uptake.

To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI

This article summarizes the role of PET imaging for detection, characterization, and theranostic/therapy planning for neuroendocrine tumors. Topics in this article span overall imaging accuracy with mostly 68Ga-DOTA-peptide imaging as well as basic principles of individualized dosimetry. There is also some discussion around further specialized approaches in dosimetry in theranostics. In addition, an overview of the literature on functional imaging in neuroendocrine tumors and the current understanding of imaging-derived clinical outcome prediction are presented.

Summary Background Conventional external beam radiotherapy is the standard palliative treatment for spinal metastases; however, complete response rates for pain are as low as 10–20%. Stereotactic body radiotherapy delivers high-dose, ablative radiotherapy. We aimed to compare complete response rates for pain after stereotactic body radiotherapy or conventional external beam radiotherapy in patients with painful spinal metastasis. Methods This open-label, multicentre, randomised, controlled, phase 2/3 trial was done at 13 hospitals in Canada and five hospitals in Australia. Patients were eligible if they were aged 18 years and older, and had painful (defined as ≥2 points with the Brief Pain Inventory) MRI-confirmed spinal metastasis, no more than three consecutive vertebral segments to be included in the treatment volume, an Eastern Cooperative Oncology Group performance status of 0–2, a Spinal Instability Neoplasia Score of less than 12, and no neurologically symptomatic spinal cord or cauda equina compression. Patients were randomly assigned (1:1) with a web-based, computer-generated allocation sequence to receive either stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions or conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions using standard techniques. Treatment assignment was done centrally by use of a minimisation method to achieve balance for the stratification factors of radiosensitivity, the presence or absence of mass-type tumour (extraosseous or epidural disease extension, or both) on imaging, and centre. The primary endpoint was the proportion of patients with a complete response for pain at 3 months after radiotherapy. The primary endpoint was analysed in the intention-to-treat population and all safety and quality assurance analyses were done in the as-treated population (ie, all patients who received at least one fraction of radiotherapy). The trial is registered with ClinicalTrials.gov , NCT02512965 . Findings Between Jan 4, 2016, and Sept 27, 2019, 229 patients were enrolled and randomly assigned to receive conventional external beam radiotherapy (n=115) or stereotactic body radiotherapy (n=114). All 229 patients were included in the intention-to-treat analysis. The median follow-up was 6·7 months (IQR 6·3–6·9). At 3 months, 40 (35%) of 114 patients in the stereotactic body radiotherapy group, and 16 (14%) of 115 patients in the conventional external beam radiotherapy group had a complete response for pain (risk ratio 1·33, 95% CI 1·14–1·55; p=0·0002). This significant difference was maintained in multivariable-adjusted analyses (odds ratio 3·47, 95% CI 1·77–6·80; p=0·0003). The most common grade 3–4 adverse event was grade 3 pain (five [4%] of 115 patients in the conventional external beam radiotherapy group vs five (5%) of 110 patients in the stereotactic body radiotherapy group). No treatment-related deaths were observed. Interpretation Stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions was superior to conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions in improving the complete response rate for pain. These results suggest that use of conformal, image-guided, stereotactically dose-escalated radiotherapy is appropriate in the palliative setting for symptom control for selected patients with painful spinal metastases, and an increased awareness of the need for specialised and multidisciplinary involvement in the delivery of end-of-life care is needed. Funding Canadian Cancer Society and the Australian National Health and Medical Research Council.

Background In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. The purpose of this study is to describe long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT). Methods Patients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were analyzed. Patients who had extrahepatic disease or previous liver transplant were excluded. Demographical, clinical, and treatment variables were analyzed. Results 128 eligible patients with HCC and MVI were treated with SBRT. Median age was 60.5 years (39 to 90 years). Baseline Child-Pugh (CP) score was A5 in 67%, A6 in 20%. Median SBRT dose was 33.3 Gy (range: 27 to 54 Gy) in 5 fractions. Local control at 1 year was 87.4% (95% CI 78.6 to 96.1%). Median overall survival (OS) was 18.3 months (95% CI 11.2 to 21.4 months); ECOG performance status > 1 (HR:1.85, p = 0.0138) and earlier treatment era (HR: 2.20, p = 0.0015) were associated with worsening OS. In 43 patients who received sorafenib following SBRT, median OS was 37.9 months (95% CI 19.5 to 54.4 months). Four patients developed GI bleeding possibly related to SBRT at 2 to 8 months, and 27% (31/112 evaluable patients) had worsening of CP class at three months after SBRT. Conclusions SBRT was associated with encouraging outcomes for patients with HCC and MVI, especially in those patients who received sorafenib after SBRT. Randomized phase III trials of SBRT with systemic and/or regional therapy are warranted and ongoing.

Purpose The Accelerated Education Program (AEP) at the Princess Margaret Cancer Centre (PM) has been offering continuing medical education courses since 2006. The purpose of this study was to assess learner experiences, perspectives, and outcomes using Kirkpatrick’s Four Level Training Evaluation Model (ie, reaction, learning, behavior, results) to ascertain whether it was meeting stated goals. Methods and Materials Past course participants (2010-2018) were invited to participate in a semistructured interview. Interviews were transcribed verbatim; thematic analysis was conducted by a 4-person research team. Results Seventeen participants including 2 medical physicists, 6 radiation oncologists, and 9 radiation therapists from 6 countries on 4 continents participated in the study. Interviews lasted an average of 25 minutes. Consistently positive outcomes were reported at each level of Kirkpatrick’s model. At the reaction level, participants liked the small, interactive case-based design, exposure to renowned faculty and practices from PM and other major centers, and the interprofessional practice (IPP) approach. Suggestions for improvements include enhancing practical content. At the learning level, participants reported gaining new knowledge or skills and new awareness or attitudes. Behavior changes described included sharing learnings with colleagues, implementing changes in practice or techniques, departmental structure, and IPP. Participants described the effects on clinical practice (results) in quality of care, access to care, and academic contribution. Identified barriers to change related to the restricted internal capacity for change and the need for wider staff training. Conclusions AEP courses were found to have a positive effect on local practices ranging from confirmation of current practice through to increased access to and quality of advanced radiotherapeutic techniques and care. Our findings confirm that AEP is achieving its goal of “putting innovation to work” and suggest curricular improvements that can enhance these effects.

PURPOSE: To determine whether quantitative PET parameters on baseline 68Ga-DOTATATE PET/CT (bPET) and interim PET (iPET) performed prior to second cycle of therapy are predictive of therapy response and progression free survival (PFS). PATIENTS & METHODS: Ninety-one patients with well-differentiated neuroendocrine tumors (mean Ki67, 8.3%) underwent 68Ga-DOTATATE PET/CT (DT- PET) to determine suitability for peptide receptor radionuclide therapy (PRRT) as part of a prospective multicenter study. Mean follow-up was 12.2 months. Of them, 36 patients had iPET. Tumor metrics evaluated: 1. Marker lesion-based measures: mean SUVmax and ratio to liver/spleen; 2. Segmented DT tumor volume (DTTV) measures: DTTV; SUVmax and SUVmean using liver and spleen as thresholds; 3. Heterogeneity parameters (coefficient of variance, kurtosis, and skewness). Wilcoxon rank sum test was used for association between continuous variables and therapy response as determined by clinical response. Univariable and multivariable Cox proportional hazards model were used for association with PFS. RESULTS: There were 71 responders and 20 non-responders. Using marker lesions, higher mean SUVmax and mean SUVmax(Tumor/Liver) were predictors of therapy response (P = 0.018 & 0.024, respectively). For DTTV, higher SUVmax and SUVmean using liver as threshold and lower kurtosis were predictors of favorable response (P = 0.025, 0.0055 & 0.031, respectively. These also correlated with longer PFS. iPET DTTV SUVmean using liver threshold and ratio iPET mean SUVmax using target lesions correlated with therapy response (P = 0.024 & 0.048, respectively) but not PFS. From the multivariable analysis adjusting for age, primary site and Ki67, mean SUVmax (P = 0.019), SUVmax T/L (P = 0.018), SUVmax T/S (P = 0.041), DTTV SUVmean Liver (P = 0.0052) and skewness (P = 0.048) remain significant predictors of PFS. CONCLUSION: Degree of somatostatin receptor expression and tumor heterogeneity as represented by several metrics in our analysis are predictive of therapy response and/or PFS. Change in these parameters after first cycle of PRRT did not correlate with clinical outcomes.

PURPOSE For many oncology training programs in low- and middle-income countries, dedicated time for research education and mentorship of trainees is limited. Here, we report a 1-year–long collaboration between a cancer center in Canada and one in Ghana with the aim of imparting clinical research skills and mentoring the research of radiation oncology residents. METHODS On the basis of a needs assessment conducted in Ghana, we designed a curriculum consisting of 13 weekly seminars delivered via videoconference, followed by a 1-year–long mentorship program to support research projects. The primary outcome was the feasibility of the program from seminars to manuscript preparation. We used multiple secondary outcomes to capture the learning experience with study-specific questionnaires. We evaluated critical thinking ability using the Berlin questionnaire. Funding was made available for research and travel to international conferences. RESULTS Five Ghanaian trainees submitted research proposals. Nine Canadian faculty members delivered the seminars and two served as methodology mentors, and two Ghanaian faculty acted as local supervisors. Feedback questionnaires from all participants showed that they agreed strongly that they would recommend the sessions to another resident (75%), that the objectives were clear (71%), and that the topics were useful for their training (73%). At the end of the program, two Ghanaian trainees finalized their manuscripts and one was published. CONCLUSION Here, we report on the implementation of a mentorship program focused on research methods and evidence-based medicine in sub-Saharan Africa. The program was successful in the drafting and publication of abstracts and manuscripts by local trainees.

Background: Trimodality therapy (TMT) with neoadjuvant chemoradiotherapy (nCRT) using concurrent carboplatin plus paclitaxel (CP) followed by surgery is the standard of care for locoregional esophageal or gastroesophageal junction (GEJ) cancers. Alternatively, nCRT with cisplatin plus fluorouracil (CF) can be used. Definitive chemoradiotherapy (dCRT) with CP or CF can be used if surgery is not planned. In the absence of comparative trials, we aimed to evaluate outcomes of CP and CF in the settings of TMT and dCRT. Methods: A single-site, retrospective cohort study was conducted at the Princess Margaret Cancer Centre to identify all patients who received CRT for locoregional esophageal or GEJ cancer. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method and multivariable Cox regression model. The inverse probability treatment weighting (IPTW) method was used for sensitivity analysis. Results: Between 2011 and 2015, 93 patients with esophageal (49%) and GEJ (51%) cancers underwent nCRT (n = 67; 72%) or dCRT (n = 26; 28%). Median age was 62.3 years and 74% were male. Median follow-up was 23.9 months. Comparing CP to CF in the setting of TMT, the OS and DFS rates were similar. In the setting of dCRT, CP was associated with significantly inferior 3-year OS (36 vs. 63%; p = 0.001; HR 3.1; 95% CI: 1.2–7.7) and DFS (0 vs. 41%; p = 0.004; HR 3.6; 95% CI: 1.4–8.9) on multivariable and IPTW sensitivity analyses. Conclusions: TMT with CF and CP produced comparable outcomes. However, for dCRT, CF may be a superior regimen.

Background Stereotactic Body Radiation Therapy (SBRT) is a non-invasive ablative treatment for hepatocellular carcinoma (HCC). This report aimed to address the limited availability of long-term outcomes after SBRT for HCC from North America. Methods Localized HCC patients without vascular invasion, who were ineligible for other liver-directed therapies and treated with SBRT at the University of Toronto or University of Michigan, were pooled to determine overall survival (OS), cumulative recurrence rates, and ≥ grade-3 toxicity. Multivariable analysis determined factors affecting OS and local recurrence rates. Results In 297 patients with 436 HCCs (42% > 3 cm), one-, three- and five-year OS was 77·3%, 39·0% and 24·1%, respectively. On Cox proportional hazards regression analysis, liver transplant after SBRT, Child–Pugh A liver function, alpha-fetoprotein ≤ 10 ng/ml, and Eastern Co-operative Oncology Group performance status 0 significantly improved OS (hazard ratio [HR] = 0·06, 95% confidence interval [CI- 0·02–0·25; p Conclusions SBRT confers high local control and long-term survival in a substantial proportion of HCC patients unsuitable for, or refractory to standard loco-regional treatments. Liver transplant should be considered if appropriate downsizing occurs after SBRT.

BACKGROUND: A microscopically positive (R1) resection margin following resection for gastric and esophageal cancers has been documented to be a poor prognostic factor. The optimal strategy and impact of different modalities of adjuvant treatment for an R1 resection margin remain unclear. METHODS: A retrospective analysis was performed for patients with gastric and esophageal adenocarcinoma treated at the Princess Margaret Cancer Centre (PMCC) from 2006–2016. Electronic medical records of all patients with an R1 resection margin were reviewed. Kaplan-Meier and Cox proportional hazards methods were used to analyze recurrence free survival (RFS) and overall survival (OS) with stage and neoadjuvant treatment as covariates in the multivariate analysis. RESULTS: We identified 69 gastric and esophageal adenocarcinoma patients with a R1 resection. Neoadjuvant chemoradiation was used in 13% of patients, neoadjuvant chemotherapy in 12%, surgery alone in 75%. Margins involved included proximal in 30%, distal in 14%, radial in 52% and multiple margins in 3% of patients. Pathological staging showed 3% with stage I disease, 20% stage II and 74% stage III. Adjuvant therapy was given in 52% of R1 pts (28% CRT, 20% chemotherapy alone, 3% radiation alone, 1% reoperation). Median RFS was 14.1 months [95% confidence interval (CI), 11.1–17.2]. The site of first recurrence was 72% distant, 12% mixed, 16% locoregional alone. Median OS was 34.5 months (95% CI, 23.3–57.9) for all patients. There was no significant difference in RFS (adjusted P=0.26) or OS (adjusted P=0.83) comparing modality of adjuvant therapy. CONCLUSIONS: Most patients with positive margins after resection for gastric and esophageal cancer had advanced pathologic stage and prognosis was poor. Our study did not find improved RFS or OS with adjuvant treatment and only one patient had reresection. The main failure pattern was distant recurrence, suggesting that patients being considered for adjuvant radiotherapy (RT) should be carefully selected. Further studies are required to determine factors to select patients with good prognosis despite a positive margin, or those who may benefit from adjuvant treatment.

The aim of this study was to determine if radiomic features combined with sarcopenia measurements on pretreatment 18 F-FDG PET/CT can improve outcome prediction in surgically treated adenocarcinoma esophagogastric cancer patients.One hundred forty-five esophageal adenocarcinoma patients with curative therapeutic intent and available pretreatment 18 F-FDG PET/CT were included. Textural features from PET and CT images were evaluated using LIFEx software ( lifexsoft.org ). Sarcopenia measurements were done by measuring the Skeletal Muscle Index at L3 level on the CT component. Univariable and multivariable analyses were conducted to create a model including the radiomic parameters, clinical features, and Skeletal Muscle Index score to predict patients' outcome.In multivariable analysis, we combined clinicopathological parameters including ECOG, surgical T, and N staging along with imaging derived sarcopenia measurements and radiomic features to build a predictor model for relapse-free survival and overall survival. Overall, adding sarcopenic status to the model with clinical features only (likelihood ratio test P = 0.03) and CT feature ( P = 0.0037) improved the model fit for overall survival. Similarly, adding sarcopenic status ( P = 0.051), CT feature ( P = 0.042), and PET feature ( P = 0.011) improved the model fit for relapse-free survival.PET and CT radiomics derived from combined PET/CT integrated with clinicopathological parameters and sarcopenia measurement might improve outcome prediction in patients with nonmetastatic esophagogastric adenocarcinoma.

Published health-related quality of life (HRQOL) outcomes are lacking in patients treated for oligo-metastatic disease (OMD). The aim of this systematic review and individual patient data meta-analysis is to determine the effect of stereotactic body radiotherapy (SBRT) on HRQOL outcomes of patients with OMD.Studies screened included adults with extra-cranial OMD, defined as ≤ 5 metastases, SBRT intended as definitive treatment, and HRQOL as primary or secondary outcome. Primary outcome was change in HRQOL at 12-months from baseline in patients with OMD who received SBRT (versus not), reported as standardized mean difference (SMD).A total of 7556 publications were identified, four studies met inclusion criteria (2 single arm interventional studies and 2 randomised controlled trials [RCTs]), and individual patient data was available from 3 studies (175 patients). In the two RCTs, there was no SS difference in the SMD between patients who received SBRT and those that did not (0.09 [95 % CI -0.32, 0.5], P = 0.66). On meta-analysis of patients (N = 107) who received SBRT the SMDwas -0.23 (95 % CI [-0.42, -0.04], versus -0.25 (95 % CI [-0.57, 0.07]) in those who did not (N = 37) receive SBRT, demonstrating a small deterioration from baseline.In patients with OMD, there is no difference in HRQOL at 12-months from baseline between patients who received SBRT and those that did not. However, a small HRQOL deterioration was found in both groups of patients. More in-depth analysis of relevant HRQOL domains, in the setting of OMD, is required to better understand the potential impact of SBRT.

There is a paucity of published health-related quality of life (HRQOL) outcomes in patients with oligometastatic disease (OMD) who receive stereotactic body radiation therapy (SBRT) and no available data assessing the effect of disease progression post-SBRT on HRQOL in this patient population.Patients with OMD who received SBRT in a phase II single-arm research ethics board approved study were included. HRQOL was a secondary outcome. This study hypothesized that there is a different pattern of change from baseline HRQOL in patients with OMD treated with SBRT that have disease progression by 12 months (progressors) compared with those that do not progress by 12 months (nonprogressors), as measured by the European Organisation of Research and Treatment in Cancer Quality of Life Questionnaire Core 30.A total of 107 patients were included in this analysis, 41 without progression and 66 with progression by 12 months; median time to progression was 7.7 (0.3-57) months. A statistically significant decline in the mean global health/quality of life (GHQOL) score (73 [SD, 21.8] to 67.2 [SD, 27.1]; P = .04) from baseline in the entire population at the 12-month follow-up was found. Mean GHQOL change score in nonprogressors was -0.8 and in progressors was -8.8 (P = .07). However, only progressors demonstrated a difference between baseline and 12-month mean GHQOL scores (71.2 vs 62.4; P = .01), which was both statistically and clinically significant (-8.8) in the range of small minimal clinically important difference. There was a higher proportion of patients who experienced a minimal clinically important difference deterioration in progressors compared with nonprogressors (37.4% vs 24.4%; P = .14).Patients who progressed by 12 months did not have a statistical or clinically significant difference in mean GHQOL change score compared with nonprogressors. However, there were signals to suggest that patients who progressed by 12 months post-SBRT experienced a different pattern of change compared with nonprogressors, which was worse compared with baseline.

Introduction Muscle sympathetic nerve activity (MSNA) controls the diameter of arterioles in skeletalmuscle, contributing importantly to the beat-to-beat regulation of blood pressure (BP). Although brain imaging studies have shown that bursts of MSNA originate in the rostral ventrolateral medulla, other subcortical and cortical structures—including the dorsolateral prefrontal cortex (dlPFC)—contribute. Hypothesis We tested the hypothesis that MSNA and BP could be modulated by stimulating the dlPFC. Method dlPFC. In 22 individuals MSNA was recorded via microelectrodes inserted into the common peroneal nerve, together with continuous BP, electrocardiographic, and respiration.Stimulation of the right (n=22) or left dlPFC (n=10) was achieved using transcranial alternating current (tcACS; +2 to −2mA, 0.08 Hz,100 cycles), applied between the nasion and electrodes over the F3 or F4 EEG sites on the scalp. Results Sinusoidal stimulation of either dlPFC caused cyclicmodulation of MSNA, BP and heart rate, and a significant increase in BP. Conclusion We have shown, for the first time, that tcACS of the dlPFC in awake humans causes partial entrainment of MSNA, heart rate and BP, arguing for an important role of this higher-level cortical area in the control of cardiovascular function.

We present results from a Lidar-based high definition 3D mapping system designed and built through optimization of a large software-controllable parameter space combining high throughput multi-channel optics with noise resistant digital encoding and processing.

This study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy.Patients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 15). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea).In total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder DStatistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.

Patients with advanced cancer often experience symptoms including pain, nausea, anorexia, fatigue, and depression. High symptom burden can be alleviated by multidisciplinary palliative care (PC) teams practicing symptom-directed management. Patients who are unable to access such services may be at higher risk of increased symptoms and poor outcomes. A sequential exploratory mixed methods study was performed to explore the burden of symptoms experienced by Northern Alberta patients with advanced cancer. The symptom burden among patients from rural and remote communities was characterized in a retrospective review capturing basic demographic and clinicopathologic information, in addition to patient-reported outcomes. Symptom prevalence was evaluated against the nature and range of supportive care services available. Service accessibility was assessed at community level by surveying health care providers (HCPs) and performing thematic analysis on their responses. From January 1 to December 31, 2017, 607 outpatients were seen in consultation in an integrated palliative radiotherapy clinic in Edmonton, Alberta. A total of 166 (27.3%) patients resided in Alberta communities designated as rural or remote. Patient-reported symptom prevalence and intensity of scores did not differ significantly between rural/remote and urban populations. Unmet practical needs were flagged significantly more often by patients from rural communities (p = 0.05). HCPs from rural community health centers in Northern Alberta were knowledgeable regarding PC services availability and referral processes within their communities. Although the symptom burden experienced by patients living with advanced cancer in rural and remote areas of Northern Alberta does not differ significantly from their urban counterparts, and community HCPs are knowledgeable regarding PC services, unmet needs within these communities remain. Continuing support for PC services in rural communities, as well as establishing care pathways for patients from rural populations traveling to urban centers to receive treatment, will help to minimize the unmet needs these patients experience.

Continuing professional development (CPD) and lifelong learning are core tenets of most healthcare disciplines. Where undergraduate coursework lays the foundation for entry into practice, CPD courses and offerings are designed to aid clinicians in maintaining these competencies. CPD offerings need to be frequently revised and updated to ensure their continued utility. The purpose of this qualitative study was to better understand the CPD needs of members of the University of Toronto's Department of Radiation Oncology (UTDRO) and determine how these needs could be generalized to other CPD programs. Given that UTDRO consists of members of various health disciplines (radiation therapist, medical physicists, radiation oncologists, etc.), eleven semi-structured interviews were conducted with various health professionals from UTDRO. Inductive thematic analysis using qualitative data processing with NVivo® was undertaken. The data was coded, sorted into categories, and subsequently reviewed for emergent themes. Participants noted that a general lack of awareness and lack of access made participation in CPD programs difficult. Members also noted that topics were often impractical, irrelevant, or not inclusive of different professions. Some participants did not feel motivated to engage in CPD offerings due to a general lack of time and lack of incentive. To address the deficiencies of CPD programs, a formal needs assessment that engages stakeholders from different centers and health professions is required. Needs assessments of CPD programs should include analyzing elements related to access, how to utilize technology-enhanced learning (TEL), determine barriers to participation, and understand how to better engage members.

Bioactivity of Bio-MA, a calcium chloride accerelator-containing calcium-silicate cement, as a pulp capping material was evaluated on mechanically exposed rat molar pulp. Sixty maxillary first molars from Wistar rats were mechanically exposed and assigned to two capping materials: Bio-MA or white mineral trioxide aggregate (WMTA), and three periods: 1, 7, or 30 days. Nine molars were exposed and covered with polytetrafluoroethylene tape, as positive controls. From histological examination, inflammatory cell infiltration and reparative dentin formation were evaluated using grading scores. No significant difference in pulpal responses between the two materials was observed at any period (p>0.05). At 1 day, all experimental groups showed localized mild inflammation. At 7 days, dentin bridge was partially observed at exposure sites with few inflammatory cells. At 30 days, pulp appeared normal with complete tubular dentin bridges. Bio-MA with accerelator was biocompatible similar to WMTA and could be used as a pulp-capping material.

The aim of current work was to present a novel evaluation procedure implemented for checking the constancy of beam path accuracy of a CyberKnife system based on ArcCHECK. A tailor‐made Styrofoam with four implanted fiducial markers was adopted to enable the fiducial tracking during beam deliveries. A simple two‐field plan and an isocentric plan were created for determining the density override of ArcCHECK in MultiPlan and the constancy of beam path accuracy respectively. Correlation curves for all diodes involved in the study were obtained by analyzing the dose distributions calculated by MultiPlan after introducing position shifts in anteroposterior, superoinferior, and left–right directions. The ability of detecting systematic position error was also evaluated by changing the position of alignment center intentionally. The one standard deviation (SD) result for reproducibility test showed the RMS of 0.054 mm and the maximum of 0.263 mm, which was comparable to the machine self‐test result. The mean of absolute value of position errors in the constancy test was measured to 0.091 mm with a SD of 0.035 mm, while the root‐mean‐square was 0.127 mm with a SD of 0.034 mm. All introduced systematic position errors range from 0.3 to 2 mm were detected successfully. Efficient method for evaluating the constancy of beam path accuracy of CyberKnife has been developed and proven to be sensitive enough for detecting a systematic drift of robotic manipulator. Once the workflow is streamlined, our proposed method will be an effective and easy quality assurance procedure for medical physicists.

Barrett’s esophagus (BE) is the primary precursor lesion of esophageal adenocarcinoma (EAC), which not only resembles the intestinal mucosa morphologically but also expresses various intestinal stem cell (ISC) markers. We hypothesized that ISC markers, Lgr5 (also a cancer stem cell marker), Ascl2 (fate determinator of ISC),Bmi1 (quiescent counterpart of Lgr5) and Cdx2 (primary regulator of ISC gene expression) have clinicopathological significance and could potentially be a predictor for survival in EAC. Methods Tissue microarray consisted of 64 EAC and 22 BE, and the expressions of Lgr5, Ascl2, Bmi1 and Cdx2 were analyzed using immunohistochemistry and scored independently by two pathologists. Clinicopathological factors (age, pathological grade and stage, affected lymph nodes, neoadjuvant therapy) were confounding factors, and univariable analysis using Fisher's exact tests as well as survival analysis using the Kaplan–Meier (KM) method and Cox proportional hazards regression (Cox PH) were performed to investigate its statistical significance. We performed a bioinformatic analysis of the TCGA dataset to validate the immunohistochemical findings. Results Among EAC, 69%, 88%, 64% and 70% expressed high Ascl2, Lgr5, Bmi1 and Cdx2, respectively. High Ascl2 and low Lgr5 expression significantly correlated to a higher number of involved lymph nodes; high Bmi1 expression significantly correlated to the pathological stage. Cdx2 was not correlated to any markers. KM analysis showed a negative impact of high Ascl2 expression on overall survival (OS; p = 0.0276) as well as progression-free survival (PFS; p = 0.0466), but not Lgr5, Bmi1 nor Cdx2. Cox PH analysis revealed Ascl2 (p = 0.011), and Cdx2 (p = 0.015) expression are independent prognostic factors for EAC. Conclusion Our results suggest that among the four ISC markers, Ascl2 and Cdx2 protein holds potential to be utilized as a prognostic biomarker. TCGA dataset revealed the association of ASCL2 mRNA expression with the number of positive lymph nodes but not overall survival, which implies further research is needed to explain the mechanism of Ascl2 overexpression in EAC carcinogenesis via ISC regulation.

BackgroundThe legal criteria for medical assistance in dying (MAiD) for adults with a grievous and irremediable medical condition were established in Canada in 2016. There has been concern that potentially reversible states of depression or demoralization may contribute to the desire for death (DD) and requests for MAiD. However, little is known about the emergence of the DD in patients, its impact on caregivers, and to what extent supportive care interventions affect the DD and requests for MAiD. The present observational study is designed to determine the prevalence, predictors, and experience of the DD, requests for MAiD and MAiD completion in patients with advanced or metastatic cancer and the impact of these outcomes on their primary caregivers.MethodsA cohort of patients with advanced or metastatic solid tumour cancers and their primary caregivers will be recruited from a large tertiary cancer centre in Toronto, Ontario, Canada, to a longitudinal, mixed methods study. Participants will be assessed at baseline for diagnostic information, sociodemographic characteristics, medical history, quality of life, physical and psychological distress, attitudes about the DD and MAiD, communication with physicians, advance care planning, and use of psychosocial and palliative care interventions. Measures will subsequently be completed every six months and at the time of MAiD requests. Quantitative assessments will be supplemented by qualitative interviews in a subset of participants, selected using quota sampling methods.DiscussionThis study has the potential to add importantly to our understanding of the prevalence and determinants of the DD, MAiD requests and completions in patients with advanced or metastatic cancer and of the experience of both patients and caregivers in this circumstance. The findings from this study may also assist healthcare providers in their conversations about MAiD and the DD with patients and caregivers, inform healthcare providers to ensure appropriate access to MAiD, and guide modifications being considered to broaden MAiD legislation and policy.

To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment.Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI 34.4cmOf the included 145 patients. 30% were sarcopenic at baseline. On the univariable Cox proportional hazards analysis, ECOG, surgical T and N staging, lymphovascular invasion (LVI) positive lymph nodes, and sarcopenia were significant prognostic factors concerning RFS and OS. On multivariable Cox regression analysis, surgical N staging (p = 0.025) and sarcopenia (p = 0.022) remained significant poor prognostic factors for OS and RFS. Combining the clinical parameters with the imaging-derived nutritional evaluation of the patient but not metabolic parameters of the tumor showed improved predictive ability for OS and RFS.Combining the patients' imaging-derived sarcopenic status with standard clinical data, but not metabolic parameters, offered an overall improved prognostic value concerning OS and RFS.

STUDY QUESTION Are follicular fluid (FF), arsenic (As), mercury (Hg), cadmium (Cd) and lead (Pb) concentrations associated with IVF outcomes among women undergoing IVF? SUMMARY ANSWER There was a non-linear association between higher FF Hg concentration and a lower likelihood of biochemical pregnancy and live birth. Higher FF Pb concentration was also associated with a lower probability of live birth. WHAT IS KNOWN ALREADY Previous research suggests that toxic elements may affect fertility among couples conceiving with and without assistance. However, the results have been inconsistent, possibly related in part to exposure misclassification. Very few studies have used ovarian FF to measure toxic elements, as it requires an invasive collection procedure, yet it may offer a more accurate estimate of a biologically effective dose than blood or urine. STUDY DESIGN, SIZE, DURATION This is a prospective study of 56 women undergoing IVF, from October 2015 to June 2017. FF was collected for analysis on the day of oocyte retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS As, Cd, Hg and Pb were determined in 197 FF specimens, using inductively coupled plasma tandem mass spectrometry. FF glutathione peroxidase, glutathione reductase, total glutathione-S-transferase, superoxide dismutase, arylesterase and paraoxonase (PON1p) activities were measured using kinetic enzyme assays. MAIN RESULTS AND THE ROLE OF CHANCE Non-linear associations were detected, in which the probabilities of biochemical pregnancy (P = 0.05) and live birth (P = 0.05) were lower in association with FF Hg greater than ∼0.51 µg/l Hg, adjusted for age, race, cigarette smoking and recent seafood consumption. Higher FF Pb was also associated with a lower likelihood of live birth (relative risk (RR) = 0.68, 95% CI: 0.46, 1.00; P = 0.05). We also found a suggestive, although imprecise, antagonizing mediating effect of PON1p activity on the association between FF Pb and live birth (−28.3%; 95% CI: −358%, 270%). LIMITATIONS, REASONS FOR CAUTION The results should be interpreted judiciously given the limited sample size and difficulty accounting for correlated data in generalized additive models and mediation analyses. Additionally, women undergoing IVF are highly selected with respect to age and socioeconomic status, and so the generalizability of the results may be limited. WIDER IMPLICATIONS OF THE FINDINGS Overall, the results suggest that FF Hg was associated with a lower likelihood of biochemical pregnancy and live birth, with a potential threshold effect, and that higher FF Pb was associated with a lower probability of live birth. These results may help to guide clinical recommendations for limiting the exposure of patients to Hg and Pb and ultimately improve IVF success rates. STUDY FUNDING/COMPETING INTEREST(S) This work was funded in part by the National Institute of Environmental Health Sciences (NIEHS), grant number 1R56ES023886-01, to the University at Albany (M.S.B.), and in part by the National Institute of Environmental Health Sciences (NIEHS), grant number 1U2CES026542-01, to the Wadsworth Center (P.J.P.). The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A

Ovarian follicular fluid serves as a biological window revealing metabolic processes in the microenvironment of a maturing oocyte, and so may offer a more accurate biomarker of biologically effecti...

Background: In Zimbabwe, the hormone receptor status is not always available when patients with breast cancer are started on treatment. Aim: This study evaluated the discordance of treatment approach in such patients, with National Comprehensive Cancer Network (NCCN) guideline recommendations as the reference standard when these results are eventually available. Setting: Female patients who presented to the Parirenyatwa Central Hospital Radiotherapy and Oncology Centre with a histological diagnosis of breast cancer, managed between 1 January 2014 and 31 December 2016. Methods: Patients with breast cancer having unknown receptor status at diagnosis, and the hormone receptor status were subsequently available either clinically or the tissues were available for study-specific analysis, were eligible for the study. The level of agreement between treatments received and the NCCN recommendations if the receptor status was known was tested using Kappa statistic. Results: Patients in stage I–III received treatment that were in strong agreement with the use of chemotherapy, and endocrine treatments with agreement scores of 1 (95% CI 0.91–1) and 0.81 (95% CI 0.65–0.95), respectively; but moderate agreement with regard to the choice of chemotherapy regimen, with a score of 0.5 (95% CI 0.32–0.68). There was a median delay of 8 (range 3–27) months for the availability of receptor status. Of the 38 stage IV patients, 33 (87%) were recommended chemotherapy. Of the 38 patients, 25 (66%) had hormone driven disease. There was somewhat agreement for use of chemotherapy, choice of chemotherapy regimen and use of endocrine treatments as initial choice with agreement scores of 0.53 (95% CI 0.36,0.69), 0.18 (95% CI 0.07, 0.35) and 0.68 (95% CI 0.51,0.82) respectively. Conclusion: Treatment approaches were largely in agreement with the NCCN guidelines for patients in stage I–III. Discordance was noted in stage IV patients with under-utilisation of hormone therapy as the initial treatment when the receptor status was unknown.

Phthalates are reproductive toxicants in experimental animal studies and exposure has been associated with infertility in human populations, although the results have been inconsistent. To help to address the data gap, we conducted a hypothesis-generating investigation of associations between urinary phthalate metabolites and reproductive outcomes among women (n = 56) and their male partners (n = 43) undergoing in vitro fertilization (IVF). Urine was collected from participants on the day of oocyte retrieval. Samples were analyzed for a series of phthalates, MEP, MBP, MPP, MHxP, MEHP, MEHHP, MECPP, MiNP, MiDP, MCHP, and MBzP, using liquid chromatography-tandem mass spectrometry. We employed Poisson regression with robust variance estimation to estimate associations between urinary phthalate levels and biochemical pregnancy and live birth, adjusted for partner's concentration and confounding factors. Doublings in women's MBP (relative risk (RR) = 0.32, 95 % CI: 0.13, 0.78), and men's MEHP (RR = 0.28, 95 % CI: 0.09, 0.83), were associated with a lower likelihood for pregnancy. Doublings in women's (RR = 0.08, 95 % CI: 0.01, 0.67) and men's (RR = 0.13, 95 % CI: 0.02, 0.92) MHxP were associated with a lower likelihood of live birth. Our results suggest that phthalate exposure may impact IVF outcomes, and underscore the importance of including male partners when investigating the impact of phthalate exposure on IVF. These results also suggest that clinical recommendations should include male partners for limiting phthalate exposure. Still, a larger and more comprehensive investigation is necessary to more definitively assess the risks.

BackgroundMEDI9197 is an intratumorally administered toll-like receptor 7 and 8 agonist. In mice, MEDI9197 modulated antitumor immune responses, inhibited tumor growth and increased survival. This first-time-in-human, phase 1 study evaluated MEDI9197 with or without the programmed cell death ligand-1 (PD-L1) inhibitor durvalumab and/or palliative radiation therapy (RT) for advanced solid tumors.Patients and methodsEligible patients had at least one cutaneous, subcutaneous, or deep-seated lesion suitable for intratumoral (IT) injection. Dose escalation used a standard 3+3 design. Patients received IT MEDI9197 0.005–0.055 mg with or without RT (part 1), or IT MEDI9197 0.005 or 0.012 mg plus durvalumab 1500 mg intravenous with or without RT (part 3), in 4-week cycles. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics, pharmacodynamics, and objective response based on Response Evaluation Criteria for Solid Tumors version 1.1. Exploratory endpoints included tumor and peripheral biomarkers that correlate with biological activity or predict response.ResultsFrom November 2015 to March 2018, part 1 enrolled 35 patients and part 3 enrolled 17 patients; five in part 1 and 2 in part 3 received RT. The maximum tolerated dose of MEDI9197 monotherapy was 0.037 mg, with dose-limiting toxicity (DLT) of cytokine release syndrome in two patients (one grade 3, one grade 4) and 0.012 mg in combination with durvalumab 1500 mg with DLT of MEDI9197-related hemorrhagic shock in one patient (grade 5) following liver metastasis rupture after two cycles of MEDI9197. Across parts 1 and 3, the most frequent MEDI9197-related adverse events (AEs) of any grade were fever (56%), fatigue (31%), and nausea (21%). The most frequent MEDI9197-related grade ≥3 events were decreased lymphocytes (15%), neutrophils (10%), and white cell counts (10%). MEDI9197 increased tumoral CD8+ and PD-L1+ cells, inducing type 1 and 2 interferons and Th1 response. There were no objective clinical responses; 10 patients in part 1 and 3 patients in part 3 had stable disease ≥8 weeks.ConclusionIT MEDI9197 was feasible for subcutaneous/cutaneous lesions but AEs precluded its use in deep-seated lesions. Although no patients responded, MEDI9197 induced systemic and intratumoral immune activation, indicating potential value in combination regimens in other patient populations.Trial registration numberNCT02556463.

Background A mainstay therapy for pain relief from uncomplicated bone metastases is external beam radiation therapy. Single fraction radiation therapy (SFRT) is more convenient and cost-effective, causes fewer acute side effects, and is equivalent to multiple fraction radiation therapy for pain relief. Despite these advantages, radiation oncologists seldom prescribe SFRT. Purpose To identify the behavioral determinants to Canadian radiation oncologists’ use of SFRT for uncomplicated bone metastases. Methods and Materials Semistructured interviews were conducted with 38 radiation oncologists from all 10 Canadian provinces. The interview guide and analysis were guided by the Theoretical Domains Framework (TDF). Transcripts were analyzed using a 5-phase thematic content analysis process: coding, generation of belief statements, generation of themes within TDF domains, generation of overarching themes, and classification of themes as barriers or facilitators to SFRT use, or as divergent (a barrier or facilitator depending on the participant). Results Thirteen overarching themes were identified of which 2 were barriers, 7 were facilitators, and 4 were divergent. The most commonly identified theme was the facilitator “most radiation oncologists are aware of evidence and guidelines on the use SFRT” (n = 38, 100%). The 3 next most reported themes (n = 37, 97.4% ) were (1) “radiation oncologists’ use of SFRT can influence their colleagues” use of it (divergent), (2) experience with SFRT can increase its use (facilitator), and (3) SFRT is convenient for patients (facilitator). The most commonly identified barrier (n = 31, 81.6%) was “SFRT is associated with a higher risk of retreatment.” Conclusions Our use of the TDF to explore the behavioral determinants of Canadian radiation oncologists’ use of SFRT for uncomplicated bone metastases identified a range of factors that are perceived to encourage and discourage its use. Our results will inform the design of future interventions to increase the use of SFRT.

The University of Toronto – Department of Radiation Oncology (UTDRO) has had a well-established Fellowship Program for over 20 years. An assessment of its graduates was conducted to evaluate training experience and perceived impact on professional development. Graduates of the UTDRO Fellowship Program between 1991 and 2015 were the focus of our review. Current employment status was collected using online tools. A study-specific web-based questionnaire was distributed to 263/293 graduates for whom active e-mails were identified; questions focused on training experience, and impact on career progression and academic productivity. As a surrogate measure for the impact of UTDRO Fellowship training, a comparison of current employment and scholarly activities of individuals who obtained their Fellow of the Royal College of Physicians of Canada (FRCPC) designation in Radiation Oncology between 2000 and 2012, with (n = 57) or without (n = 230) UTDRO Fellowship training, was conducted. Almost all UTDRO Fellowship graduates were employed as staff radiation oncologists (291/293), and most of those employed were associated with additional academic (130/293), research (53/293), or leadership (68/293) appointments. Thirty-eight percent (101/263) of alumni responded to the online survey. The top two reasons for completing the Fellowship were to gain specific clinical expertise and exposure to research opportunities. Respondents were very satisfied with their training experience, and the vast majority (99%) would recommend the program to others. Most (96%) felt that completing the Fellowship was beneficial to their career development. University of Toronto, Department of Radiation Oncology Fellowship alumni were more likely to hold university, research, and leadership appointments, and author significantly more publications than those with FRCPC designation without fellowship training from UTDRO. The UTDRO Fellowship Program has been successful since its inception, with the majority of graduates reporting positive training experiences, benefits to scholarly output, and professional development for their post-fellowship careers. Key features that would optimize the fellowship experience and its long-term impact on trainees were also identified. Electronic supplementary material The online version of this article (10.1007/s13187-020-01767-5) contains supplementary material, which is available to authorized users.

Glass Ionomer Cements (GICs) are brittle materials with low fracture toughness and strength. Therefore, understanding the fracture toughness is an important parameter to know, due to GICs being promoted for load-bearing restorations. Also, little is known about the effects of artificial saliva (AS) on fracture toughness of GICs. This project aimed to study the effects of storage and compare two different fracture toughness test methods, namely: Compact-Tension test and 4-point bending test. Samples were made from a Zinc-reinforced-GIC (ChemFil), High viscosity bulk-fill-GIC (HV) with and without LC-coating (EQUIA), Resin-Modified GIC (RM-GIC) (Riva-LC), HV-RMGIC (Riva-HV-LC) and flowable bulk-fill Giomer (Beautifil-Bulk Flowable) using a custom-made mould. Specimens were stored in either AS or distilled-water (DW) for 7 or 30 days. After storage, specimens were tested for fracture toughness. Results were analysed with Analysis of variance (ANOVA), Mann-Whitney and Weibull statistics. ANOVA showed a significant difference (P

Purpose The aim of this study was to systematically review the literature to assess the role of Ga PET imaging in neuroendocrine tumors (NETs). Materials and methods The literature was searched using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases through OVID. Studies comparing PET or PET/CT with conventional imaging in the initial diagnosis, staging and restaging, assessment of treatment response, and routine surveillance of NETs were deemed eligible for inclusion. Risk of bias and applicability concerns were assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Results Twenty-two studies met the inclusion criteria. For the initial diagnosis of NETs, PET or PET/CT had a pooled sensitivity of 91% (95% confidence interval [CI], 85%-94%) and a pooled specificity of 94% (95% CI, 86%-98%). In the setting of staging and restaging, the sensitivity of PET or PET/CT for detecting primary and/or metastatic lesions ranged from 78.3% to 100%, whereas specificity ranged from 83% to 100%. Change in management occurred in 45% (95% CI, 36%-55%) of the cases, with majority of the changes involving surgical planning and patient selection for peptide receptor radionuclide therapy. Conclusions Ga PET or PET/CT is recommended for initial diagnosis where conventional testing remained equivocal, for staging of patients with localized primary and/or limited metastasis where definitive surgery is planned, to determine somatostatin receptor status and suitability for peptide receptor radionuclide therapy, and for staging of patients where detection of occult disease will alter treatment options and decision making.

Background This study aimed to fabricate a denture base resin (DBR) containing phytoncide microcapsules (PTMCs) and determine the mechanical properties of the resin and antifungal activity. Methods Fifty‐four heat cured rectangular DBR specimens (64 x 10 x 3.3 ± 0.2 mm) containing nine concentrations of PTMC between 0 ‐ 5% (wt/wt) were fabricated and subjected to a three‐point bending test. A phytoncide release bioassay was developed using DBR containing 0% and 2.5% PTMCs (wt/wt) in a 24 well‐plate assay with incubation of Porphyromonas gingivalis at 37°C for 74 h. The antifungal activity of PTMCs against Candida albicans, in a pH 5.5 acidic environment was determined in a plate assay. Results Flexural strength decreased with increasing PTMC concentration from 97.58 ± 4.79 MPa for the DBR alone to 53.66 ± 2.46 MPa for DBR containing 5.0% PTMC. No release of phytoncide from the PTMCs in the DBR was detected at pH 7.4. The PTMCs had a minimal inhibitory concentration of 2.6% (wt/vol) against C. albicans at pH 5.5. Conclusions PTMCs can be added to DBR 2.5% (wt/wt) without adversely affecting flexural strength. PTMCs released the antimicrobial agent at pH 5.5 at concentrations sufficient to inhibit the growth of the C. albicans.

The practice of radiation oncology is primarily based on precise technical delivery of highly conformal, image-guided external beam radiotherapy or brachytherapy. However, systematic research efforts are being made to facilitate individualised radiation dose prescriptions on the basis of gene-expressssion profiles that reflect the radiosensitivity of tumour and normal tissue. This advance in precision radiotherapy should complement those benefits made in precision cancer medicine that use molecularly targeted agents and immunotherapies. The personalisation of cancer therapy, predicated largely on genomic interrogation, is facilitating the selection of therapies that are directed against driver mutations, aberrant cell signalling, tumour microenvironments, and genetic susceptibilities. With the increasing technical power of radiotherapy to safely increase local tumour control for many solid tumours, it is an opportune time to rigorously explore the potential benefits of combining radiotherapy with molecular targeted agents and immunotherapies to increase cancer survival outcomes. This theme provides the basis and foundation for this American Society for Radiation Oncology guideline on combining radiotherapy with molecular targeting and immunotherapy agents.

// Ali Hosni 1 , Kathy Han 1 , Lisa W. Le 2 , Jolie Ringash 1 , James Brierley 1 , Rebecca Wong 1 , Robert Dinniwell 1 , Anthony Brade 1 , Laura A. Dawson 1 , Bernard J. Cummings 1 , Monika K. Krzyzanowska 3 , Eric X. Chen 3 , David Hedley 3 , Jennifer Knox 3 , Alexandra M. Easson 4 , Patricia Lindsay 1 , Tim Craig 1 and John Kim 1 1 Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada 2 Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada 3 Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada 4 Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada Correspondence to: John Kim, email: john.kim@rmp.uhn.ca Keywords: anal cancer; chemoradiotherapy; IMRT; pattern of failure; outcomes Received: November 11, 2017 Accepted: February 27, 2018 Published: April 17, 2018 ABSTRACT Purpose: Patterns of failure and long term outcomes were prospectively evaluated following tumor factors-stratified radiation dose for anal/perianal cancer. Methods: Between 2008–2013, patients with anal/perianal squamous cell carcinoma were accrued to an institutional REB-approved prospective study. All patients were treated with image-guided intensity-modulated radiation therapy (IG-IMRT). Radiation dose selection (27–36 Gy for elective target, and 45–63 Gy for gross target) was based on tumor clinico-pathologic features. Chemotherapy regimen was 5-fluorouracil/mitomycin-C (weeks 1&5). Local [LF], regional failure [RF], distant metastasis [DM], overall- [OS], disease-free [DFS], colostomy-free survival [CFS] and late toxicity were analyzed. Results: Overall, 101 patients were evaluated; median follow-up: 56.5 months; 49.5% male; 34.7% T3/4-category, and 35.6% N+. Median radiation dose was 63 Gy. The most common acute grade ≥3 toxicities were skin (41.6%) and hematological (30.7%). Five-year OS, DFS, CFS, LF, RF, DM rates were 83.4%, 75.7%, 74.7, 13.9%, 4.6% and 5% respectively. Five-year LF for patients with T1-2 and T3-4 disease were 0% and 39.2% respectively. All LF ( n = 14, after 63 Gy, in tumors ≥5 cm) were in the high dose volume except one marginal to the high dose volume. All RF ( n = 4) were within elective dose volume except one within the high dose volume. On multivariable analysis, T3/4-category predicted for poor DFS, CFS and OS. The overall late grade ≥3 toxicity was 36.2% (mainly anal [20%]). Conclusions: Individualized radiation dose selection using IG-IMRT resulted in good long term outcomes. However, central failures remain a problem for locally advanced tumors even with high dose radiation (63 Gy/7weeks).