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Background: The burden of heart failure (HF) is high globally, but information on its burden in the Eastern Mediterranean Region (EMR) is limited. This study provides a systematic analysis of the burden and underlying causes of HF in the EMR, including at the country level, between 1990 and 2019., Methods: We used the 2019 Global Burden of Disease (GBD) data for estimates of prevalence, years lived with disability (YLDs), and underlying causes of HF in the EMR. Age-standardised prevalence, YLDs, and underlying causes of HF were compared by 5-year age groups (considering 15 years old and more), sex (male and female), and countries., Findings: In contrast with the decreasing trend of HF burden globally, EMR showed an increasing trend. Globally, the HF age-standardised prevalence and YLDs decreased by 7.06% (95% UI: -7.22%, -6.9%) and 6.82% (95% UI: -6.98%, -6.66%) respectively, from 1990 to 2019. The HF age-standardised prevalence and YLDs in the EMR in 2019 were 706.43 (95% UI: 558.22-887.87) and 63.46 (95% UI: 39.82-92.59) per 100,000 persons, representing an increase of 8.07% (95% UI: 7.9%, 8.24%) and 8.79% (95% UI: 8.61%, 8.97%) from 1990, respectively. Amongst EMR countries, the age-standardised prevalence and YLDs were highest in Kuwait, while Pakistan consistently had the lowest HF burden. The dramatic increase of the age-standardised prevalence and YLDs were seen in Oman (28.79%; 95% UI: 28.51%, 29.07% and 29.56%; 95% UI: 29.28%, 29.84%), while Bahrain witnessed a reduction over the period shown (-9.66%; 95% UI: -9.84%, -9.48% and-9.14%; 95% UI: -9.32%, -8.96%). There were significant country-specific differences in trends of HF burden from 1990 to 2019. Males had relatively higher rates than females in all age groups. Among all causes of HF in 2019, ischemic heart disease accounted for the highest age-standardised prevalence and YLDs, followed by hypertensive heart disease., Interpretation: The burden of HF in the EMR was higher than the global, with increasing age-standardised prevalence and YLDs in countries of the region. A more comprehensive approach is needed to prevent underlying causes and improve medical care to control the burden of HF in the region., Funding: None., Competing Interests: SMSI declares grants from the National Health and Medical Research Council, and the National Heart Foundation. All other authors declare no competing interests., (© 2022 The Authors.)

Objectives: Percutaneous endoscopic gastrostomy (PEG) placement is essential for the provision of enteral nutrition in select head and neck cancer (HNC) patients. Minimally invasive tube placement is facilitated through one of two techniques, push or pull, but there have been conflicting results regarding safety profiles of these procedures. The objectives of this study were to determine the association of PEG insertion technique with gastrostomy tube complications, including stomal metastases., Methods: A multi-institutional retrospective cohort study of patients with HNC undergoing PEG insertion by either the pull (gastroscope assisted) or push (fluoroscopy assisted) technique was performed. Tube-related complications included infection, dislodgement, deterioration, leak, and other. Adjusted analysis was performed via a multivariable logistic regression model., Results: 1,575 patients were included across three institutions. Tube-related complications occurred in 36% of patients, the most common being peristomal leak (13%) and infection (16%). The push technique (OR 2.66, 95% CI: 1.42-4.97), and the presence of T4 disease (OR 4.62, 95% CI: 1.58-13.51), were associated with a greater risk of developing any tube-related complication. Infection rates were similar between pull and push cohorts. All detected stoma metastases occurred with the pull technique, with an overall prevalence of 0.32% amongst the cohort., Conclusions: The push technique is associated with a greater risk of developing any tube-related complication, but the rate of stomal metastases may be higher with the pull technique. There is potential for quality improvement measures to improve tube-related complications associated with either technique., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: Tumor and target volume manual delineation remains a challenging task in head and neck cancer radiation therapy. The purpose of this study was to conduct a multi-institutional evaluation of manual delineations of gross tumor volume (GTV), high-risk clinical target volume (CTV), parotids, and submandibular glands on treatment simulation magnetic resonance scans of patients with oropharyngeal cancer., Methods and Materials: We retrospectively collected pretreatment T1-weighted, T1-weighted with gadolinium contrast, and T2-weighted magnetic resonance imaging scans for 4 patients with oropharyngeal cancer under an institution review board-approved protocol. We provided the scans to 26 radiation oncologists from 7 international cancer centers that participated in this delineation study. We also provide the patients' clinical history and physical examination findings, along with a medical photographic image and radiologic results. We used both the Simultaneous Truth and Performance Level Estimation algorithm and pair-wise comparisons of the contours, using overlap/distance metrics. Lastly, to assess experience and CTV delineation institutional practices, we had participants complete a brief questionnaire., Results: Large variability was measured between observers' delineations for GTVs and CTVs. The mean Dice similarity coefficient values across all physicians' delineations for GTVp, GTVn, CTVp, and CTVn were 0.77, 0.67, 0.77, and 0.69, respectively, for Simultaneous Truth and Performance Level Estimation algorithm comparison, and 0.67, 0.60, 0.67, and 0.58, respectively, for pair-wise analysis. Normal tissue contours were defined more consistently when considering overlap/distance metrics. The median radiation oncology clinical experience was 7 years. The median experience delineating on magnetic resonance imaging was 3.5 years. The GTV-to-CTV margin used was 10 mm for 6 of 7 participant institutions. One institution used 8 mm, and 3 participants (from 3 different institutions) used a margin of 5 mm., Conclusions: The data from this study suggests that appropriate guidelines, contouring quality assurance sessions, and training are still needed for the adoption of magnetic resonance-based treatment planning for head and neck cancers. Such efforts should play a critical role in reducing delineation variation and ensure standardization of target design across clinical practices., (Copyright © 2022. Published by Elsevier Inc.)

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown., Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC., Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up., Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings)., Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects., Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively)., Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes., Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Purpose: Radiation dermatitis (RD) is a side effect experienced by many patients undergoing radiotherapy (RT) for breast cancer. In the present study, the Edmonton Symptom Assessment System (ESAS), a validated patient-reported symptom screening tool, was used to determine the impacts of RT-induced skin outcomes on ESAS items. Patient- and treatment-related factors and skin treatments to manage RD symptoms, were assessed for association with ESAS scores., Methods: Patient and treatment characteristics were collected retrospectively for breast cancer patients treated with adjuvant RT between December 2013 and November 2015. Prospective data was collected through clinician-reported surveys. Linear regression analyses were performed to detect the relationship between patient-reported ESAS scores and clinician-reported RD symptoms., Results: A total of 857 patients were included in the analysis. Moderate to severe scores were commonly reported for fatigue (n = 412, 48%), wellbeing (n = 386, 45%) and anxiety (n = 266, 31%). Oral analgesic use was associated with ESAS fatigue, drowsiness, pain, nausea, lack of appetite, shortness of breath, and wellbeing (P < .05), while dressings were only associated with anxiety (P = .02). No RD symptoms were found to be significantly associated with any ESAS items., Conclusions: The ESAS accurately reflects symptoms of fatigue, anxiety, and wellbeing for breast cancer patients undergoing RT. Our study, however, found no association between ESAS scores and RD severity, which may reflect the shortcomings of the ESAS in assessing symptom burden. Further research is necessary to warrant the development of a new site-specific symptom screening tool for use in RT for breast cancer., (Copyright © 2021. Published by Elsevier Inc.)

Importance: Patients with head and neck cancer manage a variety of symptoms at home on an outpatient basis. Clinician review alone often leaves patient symptoms undetected and untreated. Standardized symptom assessment using patient-reported outcomes (PROs) has been shown in randomized clinical trials to improve symptom detection and overall survival, although translation into real-world settings remains a challenge., Objective: To better understand how patients with head and neck cancer cope with cancer-related symptoms and to examine their perspectives on standardized symptom assessment., Design, Participants, and Setting: This was a qualitative analysis using semistructured interviews of patients with head and neck cancer and their caregivers from November 2, 2020, to April 16, 2021, at a regional tertiary center in Canada. Purposive sampling was used to recruit a varied group of participants (cancer subsite, treatment received, sociodemographic factors). Drawing on the Supportive Care Framework, a thematic approach was used to analyze the data. Data analysis was performed from November 2, 2020, to August 2, 2021., Main Outcomes and Measures: Patient perception of ambulatory symptom management and standardized symptom assessment., Results: Among 20 participants (median [range] age, 59.5 [33-74] years; 9 [45%] female; 13 [65%] White individuals), 4 themes were identified: (1) timely physical symptom management, (2) information as a tool for symptom management, (3) barriers to psychosocial support, and (4) external factors magnifying symptom burden. Participants' perceptions of standardized symptom assessment varied. Some individuals described the symptom monitoring process as facilitating self-reflection and symptom detection. Others felt disempowered by the process, particularly when symptom scores were inconsistently reviewed or acted on., Conclusions and Relevance: This qualitative analysis provides a novel description of head and neck cancer symptom management from the patient perspective. The 4 identified themes and accompanying recommendations serve as guides for enhanced symptom monitoring.

Management of locoregionally advanced head and neck cancers (HNCs) remains a challenge. Some groups have attempted to use stereotactic radiotherapy (SBRT) to deliver "boost" treatment following conventional radiotherapy to improve local control (LC) and overall survival (OS), while aiming for acceptable toxicities. Medline, EMBASE, and Cochrane Library databases were queried for SBRT as curative-intent planned boost in HNC after conventional radiotherapy. Individual studies were reviewed from inception until January 2021, extracting patient, treatment, and outcome data. Nine studies met inclusion criteria, representing 454 unique patients treated with curative intent across multiple head and neck sites with conventional radiotherapy. At 3 years, median LC was 92% (90%-98%), and median OS was 80% (75%-91%). Seven treatment-related grade 5 toxicities (1.5%) were reported. Despite acceptable LC and OS rates, there were severe treatment-related late toxicities. As such, SBRT boost should only be used in investigational settings until more data is available., (© 2021 Wiley Periodicals LLC.)

Purpose: Breast cancer patients receiving adjuvant radiotherapy (RT) benefit from local control. However, RT can give rise to increased fatigue, lowering quality of life. The aim of this study was to prospectively identify trends and risk factors in patient-reported fatigue associated with breast RT., Material and Methods: Patients were assessed using the Edmonton Symptom Assessment Scale (ESAS) before, once per week during RT, up to 6 weeks after RT completion, and 1-3 months post RT. Patients were included in the analysis if the ESAS was completed before, at least once during, and at least once after RT., Results: A total of 651 patients were included. Fatigue scores increased significantly during weeks 1-3 (p < 0.001) and weeks 5-6 (p < 0.0001) during RT compared to baseline. After RT completion, fatigue scores did not change significantly compared to baseline. Mastectomy patients who received previous chemotherapy experienced significantly more fatigue compared to mastectomy patients without previous chemotherapy (p = 0.0002). Patients less than 50 (p = 0.002), 50-59 (p = 0.007), or 60-69 (p = 0.048) years of age at RT start were more likely to have higher proportions of moderate or severe fatigue compared to patients ≥ 70 years of age., Conclusions: Fatigue associated with breast irradiation increased up to 6 weeks during RT and returned to near baseline scores at 1-3 months post treatment. Given that fatigue was significant in mastectomy patients, further research is needed to reduce fatigue among this cohort, especially those who have received previous chemotherapy and younger patients who are receiving breast RT., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Synchronous bilateral breast cancer (SBBC) is rare and there is little evidence describing organs at risk (OAR) and limits to the heart and lungs caused by radiotherapy (RT). Quantifying mean heart dose (MHD) and mean lung dose (MLD) from RT in this patient cohort may lead to better understanding of doses to OAR and resultant effects on clinical outcomes. The primary objective was to assess median MHD and MLD in SBBC, while secondary aims included analyses of 1) factors associated with MHD and MLD, 2) V5 and V20 values and 3) factors associated with clinical outcomes., Methods: Patients planned for adjuvant bilateral whole breast/chest wall (WB) RT from a single institution treated in 2011-2018 were included. Median MHD and MLD (Gy) were stratified by hypofractionated (42.56 Gy/16 fractions, HFRT) and conventional fractionation (50 Gy/ 25 fractions, CFRT) and summarized separately based on the following treatments: 1) locoregional RT, WB tangential RT either 2) no boost 3) sequential boost or 4) simultaneous integrated boost. MHD, MLD, lung V5 and V20 values, and demographics were collected. Linear regression analyses identified factors associated with MHD and MLD and factors associated with clinical outcomes., Results: A total of 88 patients were included. The median MHD for HFRT and CFRT was 1.99 Gy and 2.94 Gy, respectively. The median MLD for HFRT and CFRT was 6.00 Gy and 10.08 Gy, respectively. MHD and MLD were significantly associated with the occurrence of a cardiac or pulmonary event post-radiation. Patients who had a mastectomy or tumoral muscle involvement were more likely to develop a local recurrence, metastasis or new primary while patients who had a lumpectomy or tumor with a positive estrogen receptor status were less likely to experience these events., Conclusions: Further investigation should be conducted to identify SBBC RT techniques that mitigate dose to OARs to improve clinical outcomes in bilateral breast patients., (Copyright © 2021. Published by Elsevier Inc.)

Aim: To report outcomes of Stereotactic Body Radiotherapy (SBRT) for head and neck skin cancer (HNSC) patients treated at a high-volume center., Materials: A retrospective review of HNSC SBRT patients from 2012 to 2019 was conducted. Kaplan-Meier method was used to estimate local control (LC), locoregional control (LRC) outside of SBRT field, overall survival (OS), progression-free survival (PFS) and late toxicity (LT). Univariate and multivariate analyses were performed. Grade 3-4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0., Results: One hundred and six medically unfit HNSC patients (112 lesions) were included. Median follow-up was 8 months. Median patient age at diagnosis was 86 years (range: 56-102 years). The majority of patients had advanced disease (overall stage III-IV [n = 90, 85%]) with median gross tumor volumes (GTV) of 31 cm 3 (range: 17-56 cm 3 ). Treated sites were: primary (n = 51), nodal (n = 47) or primary plus nodal (n = 8). SBRT doses ranged from 32-50 Gy delivered twice weekly in 4-6 fractions to the gross tumor volume (GTV). One and 2-year LC rates were 78% (69-88) and 67% (53-82), respectively. One-year LRC outside of SBRT field, OS, PFS and LT rates were 72% (62-84), 53% (43-65), 52% (40-62), and 7% (2-17), respectively. Thirty-three patients (31%) developed acute grade ≥ 3 treatment-related toxicity, most commonly dermatitis (n = 31). Nine patients (8%) experienced late grade ≥ 3 toxicity, including 7 grade 3 fibrosis, 1 grade 3 bone radionecrosis and 1 grade 4 skin ulceration. No treatment-related deaths (grade 5) were observed., Conclusion: SBRT provides durable disease control with acceptable toxicity for medically unfit high-risk HNSC patients unable to undergo standard of care curative treatment approaches., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Objective: Symptom burden is common in head and neck cancer patients though it frequently remains undetected and untreated. The Edmonton Symptom Assessment System - revised version (ESAS-r) is a generic symptom scale deployed in many outpatient settings worldwide. The ESAS-r is meant to improve symptom detection and management. We sought to review the ESAS-r and its psychometric properties in a head and neck oncology population., Methods: Narrative Review., Results: Over the past 30 years, the ESAS-r has emerged as one of the most used symptom scales for cancer patients. Its psychometric properties in a heterogenous cancer population are well supported, proving to be reliable and valid in a variety of settings. The linking of ESAS-r scores with Ontario administrative health data has led to a detailed assessment of validity in head and neck cancer. The ESAS-r can discriminate between high and low levels of symptom burden and is responsive to change over time in this patient population. ESAS-r scores have also been shown to be a strong predictor of future emergency department use and unplanned hospitalization in head and neck cancer patients., Conclusions: The ESAS-r is reliable and valid in the head and neck cancer population and may serve as a useful clinical endpoint in research studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Purpose: Breast cancer patients frequently develop radiation dermatitis (RD) when undergoing post-operative radiation therapy (RT). Traditional RD assessment methods measure clinician-reported outcomes (CROs), but patient-reported outcomes (PROs) have gained recent popularity. The purpose of this prospective analysis was to compare PROs with CROs of breast RD., Materials and Methods: Demographic and treatment characteristics were prospectively collected for patients receiving post-operative RT between February 2018 to September 2020. Patients and clinicians completed a skin symptom assessment at baseline, weekly during RT, and at a one- to three-month follow-up visit. Skin treatments used by patients were collected. Concordance between each PRO and CRO was determined using percent concordance and concordance index (C-statistic) by logistic regression analysis., Results: A total of 777 patients were included in the present study. All skin symptom assessment items were significantly underreported by clinicians in comparison to patients (p < 0.0001), with a low to moderate level of concordance (C-statistic range: 0.58-0.70; percent concordance range: 29-50%). The majority of patients used moisturizing creams as a prophylactic measure (65.1%), as per institutional guidelines., Conclusion: There were significant discrepancies between PROs and CROs when assessing breast RD. CROs alone are insufficient in measuring RD as they fail to capture the impact on patient quality of life. The study findings highlight the need for improved RD symptom assessment and support the development of a new tool with both patient and clinician components., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: This review aimed to assess the quality and efficacy of tools currently used in breast cancer patients to score radiation dermatitis (RD), a common debilitating side effect of radiotherapy (RT)., Methods: A search was conducted through Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials databases on 14 February 2020. English articles that evaluated an instrument's use in assessing RD among breast cancer patients receiving external beam RT were included. Studies that reported on the reliability, validity, or concordance of items between assessment tools were included in accordance with the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) criteria., Results: Twelve studies were included in this review, with a total of 13 skin toxicity assessment tools discussed. Tools that assessed clinician-reported outcomes (CROs) mostly reported moderate correlation with biophysical parameter (BP) measurements and low correlation with patient-reported outcomes (PROs). Traditionally used CRO scoring tools demonstrated moderate inter-rater reliability between clinicians, likely due to the subjective nature of items on the grading scales. Most commonly used tools were found to be either insufficient or indeterminate in their measurement properties., Conclusions: Current standardized tools that measure CROs are subject to clinician interpretation and fail to represent the patient experience. Tools designed to assess PROs are promising in their assessments of the impact of RT on patient quality of life; however, most PRO tools are generic to all skin conditions and require further validation for use in breast cancer. Among tools that measure CROs, PROs, and BPs, there is insufficient evidence on their measurement properties to establish a "gold standard" for the assessment of RD in breast cancer patients.

This prospective study was conducted to investigate the role of quantitative ultrasound (QUS) radiomics in predicting recurrence for patients with node-positive head-neck squamous cell carcinoma (HNSCC) treated with radical radiotherapy (RT). The most prominent cervical lymph node (LN) was scanned with a clinical ultrasound device having central frequency of 6.5 MHz. Ultrasound radiofrequency data were processed to obtain 7 QUS parameters. Color-coded parametric maps were generated based on individual QUS spectral features corresponding to each of the smaller units. A total of 31 (7 primary QUS and 24 texture) features were obtained before treatment. All patients were treated with radical RT and followed according to standard institutional practice. Recurrence (local, regional, or distant) served as an endpoint. Three different machine learning classifiers with a set of maximally three features were used for model development and tested with leave-one-out cross-validation for nonrecurrence and recurrence groups. Fifty-one patients were included, with a median follow up of 38 months (range 7-64 months). Recurrence was observed in 17 patients. The best results were obtained using a k-nearest neighbor (KNN) classifier with a sensitivity, specificity, accuracy, and an area under curve of 76%, 71%, 75%, and 0.74, respectively. All the three features selected for the KNN model were texture features. The KNN-model-predicted 3-year recurrence-free survival was 81% and 40% in the predicted no-recurrence and predicted-recurrence groups, respectively. (p = 0.001). The pilot study demonstrates pretreatment QUS-radiomics can predict the recurrence group with an accuracy of 75% in patients with node-positive HNSCC. Clinical trial registration: clinicaltrials.gov.in identifier NCT03908684., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

To investigate the role of quantitative ultrasound (QUS) radiomics to predict treatment response in patients with head and neck squamous cell carcinoma (HNSCC) treated with radical radiotherapy (RT). Five spectral parameters, 20 texture, and 80 texture-derivative features were extracted from the index lymph node before treatment. Response was assessed initially at 3 months with complete responders labelled as early responders (ER). Patients with residual disease were followed to classify them as either late responders (LR) or patients with persistent/progressive disease (PD). Machine learning classifiers with leave-one-out cross-validation was used for the development of a binary response-prediction radiomics model. A total of 59 patients were included in the study (22 ER, 29 LR, and 8 PD). A support vector machine (SVM) classifier led to the best performance with accuracy and area under curve (AUC) of 92% and 0.91, responsively to define the response at 3 months (ER vs. LR/PD). The 2-year recurrence-free survival for predicted-ER, LR, PD using an SVM-model was 91%, 78%, and 27%, respectively (p < 0.01). Pretreatment QUS-radiomics using texture derivatives in HNSCC can predict the response to RT with an accuracy of more than 90% with a strong influence on the survival.Clinical trial registration: clinicaltrials.gov.in identifier NCT03908684.

Purpose: This study investigated the use of quantitative ultrasound (QUS) obtained during radical radiotherapy (RT) as a radiomics biomarker for predicting recurrence in patients with node-positive head-neck squamous cell carcinoma (HNSCC)., Methods: Fifty-one patients with HNSCC were treated with RT (70 Gy/33 fractions) (±concurrent chemotherapy) were included. QUS Data acquisition involved scanning an index neck node with a clinical ultrasound device. Radiofrequency data were collected before starting RT, and after weeks 1, and 4. From this data, 31 spectral and related-texture features were determined for each time and delta (difference) features were computed. Patients were categorized into two groups based on clinical outcomes (recurrence or non-recurrence). Three machine learning classifiers were used for the development of a radiomics model. Features were selected using a forward sequential selection method and validated using leave-one-out cross-validation., Results: The median follow up for the entire group was 38 months (range 7-64 months). The disease sites involved neck masses in patients with oropharynx (39), larynx (5), carcinoma unknown primary (5), and hypopharynx carcinoma (2). Concurrent chemotherapy and cetuximab were used in 41 and 1 patient(s), respectively. Recurrence was seen in 17 patients. At week 1 of RT, the support vector machine classifier resulted in the best performance, with accuracy and area under the curve (AUC) of 80% and 0.75, respectively. The accuracy and AUC improved to 82% and 0.81, respectively, at week 4 of treatment., Conclusion: QUS Delta-radiomics can predict higher risk of recurrence with reasonable accuracy in HNSCC.Clinical trial registration: clinicaltrials.gov.in identifier NCT03908684., Competing Interests: Gregory Czarnota received funding from Terry Fox Foundation Program Project Grant from the Hecht Foundation (grant number 1083). None of the other authors have any other conflict of interest to declare., (© 2021 The Authors.)

Purpose: To determine the association between patient-reported symptom burden and subsequent emergency department use and unplanned hospitalization (ED/Hosp) in a head and neck cancer (HNC) patient population., Methods: This was a population-based study of patients diagnosed with HNC who had completed at least one outpatient Edmonton Symptom Assessment System (ESAS) assessment between January 2007 and March 2018 in Ontario, Canada. Logistic regression models were used to determine the relationship between outpatient ESAS scores and subsequent 14-day ED/Hosp use. A generalized estimating equation approach with an exchangeable correlation structure was incorporated to account for patient-level clustering., Results: There were 11,761 patients identified, completing a total of 73,282 ESAS assessments and experiencing 5,203 ED/Hosp events. Six of the nine ESAS symptom scores were positively associated with ED/Hosp use, with pain, appetite, shortness of breath, and tiredness demonstrating the strongest associations. A global ESAS score was calculated by selecting the highest individual symptom score (h-ESAS). Among patients reporting a maximum h-ESAS score of 10, 15.1% had an ED/Hosp event within 14 days compared with 1.5% for those with the lowest possible score of zero. In adjusted analysis, the odds of ED/Hosp use increased with h-ESAS (1.23 per one-unit increase [95% CI, 1.22 to 1.25]). When treated as a categorical variable, patients with the maximum h-ESAS score of 10 had 9.23 (95% CI, 7.22 to 11.33) higher odds of ED/Hosp use, relative to the minimum score of zero., Conclusion: ESAS scores are strongly associated with subsequent ED/Hosp events in patients with HNC. Clinician education around how ESAS data might inform patient care may enhance symptom detection and management.

Purpose: The Edmonton Symptom Assessment Scale (ESAS) is a validated tool used in patients with varied cancer diagnoses to measure patient symptoms. The present manuscript will review the literature assessing the ability of the ESAS to predict patient-related outcomes in breast cancer patients., Methods: A literature search was conducted of Cochrane Central Register of Controlled Trials databases, Ovid MEDLINE, and Embase for English articles that investigated the use of predictive modelling with the ESAS in the breast cancer population. Study type, publication year, sample size, patient demographics, predicted outcomes, and strongest predictive factors/symptoms were summarized for each study., Results: A total of nine articles were included in this review. Five articles used the ESAS in predictive models to determine patient time to death. ESAS was also used to predict emergency department visits, determine symptoms associated with decreased quality of life, and generate a Health Utility Score. Lack of appetite was the most common ESAS symptom, as it was reported in five studies to be associated with decreased survival. In four of the nine articles, an additional survey investigating physical functioning was used in combination with ESAS to strengthen the predictive models., Conclusions: Included studies support the use of ESAS in predictive models, particularly for predicting survival. Using the ESAS as a predictive tool allows for more accurate time to death predictions, potentially improving symptom management and preventing overtreatment of palliative patients near the end of life.

Purpose: Severe radiation dermatitis (RD) is distressing and may have adverse long-term effects including fibrosis and telangiectasia. Treatment interruptions due to severe RD may increase the risk of recurrence. Two randomized trials of Mepitel film demonstrated efficacy in preventing severe RD in breast cancer, but this product has not been widely adopted in North America. We aimed to assess the feasibility and efficacy of Mepitel film for prevention of breast RD at a Canadian center., Methods and Materials: Patients were stratified based on breast size and receipt of postmastectomy radiation therapy. The primary outcome was RD grade using the Common Terminology Criteria for Adverse Events. Secondary outcomes included moist desquamation, patient- and clinician-reported symptoms of skin toxicity, and cosmetic outcomes., Results: Thirty patients receiving external beam radiation therapy to the breast or chest wall were enrolled. Two patients (6.7%) discontinued use of the Mepitel film before completing radiation therapy. No patients developed grade 3 RD or higher. Five patients (17.9%) developed grade 2 RD: 3 (10.7%) had moist desquamation, and 2 (7.1%) had brisk erythema without moist desquamation., Conclusions: Mepitel film completely prevented grade 3 RD. Rates of moist desquamation and grade 2 RD were lower with Mepitel film than in studies using aqueous cream, but unlike previous trials of Mepitel film we did not achieve complete prevention of moist desquamation. Further research is needed to confirm the efficacy of Mepitel film versus standard prophylaxis for RD and identify the patients who will benefit the most from the film., (Copyright © 2020 American Society for Radiation Oncology. All rights reserved.)

Purpose: Breast cancer patients receiving radiotherapy (RT) commonly report pain, contributing to physical and emotional distress, and potentially resulting in poor quality of life. This study prospectively identified trends and risk factors in patient-reported pain associated with breast irradiation using the Edmonton Symptom Assessment Scale (ESAS) and a study-specific Skin Symptom Assessment (SSA)., Methods: Before RT and once per week during RT, patients completed the ESAS and SSA. Upon RT completion, patients were contacted via telephone to complete both assessments weekly for 6 weeks, and a final assessment was conducted 1-3 months post-RT. Only data from patients who had completed both assessments before, at least once during, and at least once after RT were included in our analysis., Results: A total of 426 patients provided data for the analysis. Overall acute pain increased significantly at week 1-2 (p < 0.0001), week 5 (p = 0.0011), and at 1-3 months (p < 0.0001) post-RT compared with baseline, and acute breast pain increased significantly at week 1 (p < 0.001) and week 2 (p = 0.0002) post-RT compared with baseline. Previous chemotherapy (adjuvant or neoadjuvant) in mastectomy patients was associated with increased overall pain compared with mastectomy patients without previous chemotherapy (p = 0.017). Younger patients (40-49 or 50-59 years of age) reported more overall pain (p = 0.0001, p = 0.038) and breast pain (p = 0.0003, p = 0.0038) compared with patients ≥ 60 years of age., Conclusions: Patient-reported pain associated with breast irradiation peaked 1 week after RT completion. Our findings provide support for closer monitoring of acute pain associated with breast RT in younger patients.

Purpose: Radiation dermatitis (RD) is a side effect that frequently arises during radiotherapy (RT) in breast cancer patients. The present study investigates possible predictive factors of RD, as well as the use of skin treatments to manage symptoms., Methods: Demographic and treatment characteristics were collected retrospectively, while skin symptoms and treatments were collected prospectively for patients who received adjuvant RT between December 2013 and November 2015. Patients were seen weekly by clinicians throughout treatment, during which a clinician-reported survey was completed on RD symptoms and skin treatments. Possible predictive factors were correlated with skin outcomes through a univariate ordinal logistic regression analysis., Results: A total of 1093 patients were included in this analysis. Predictive factors for erythema included dose fractionation (p<0.0001), tissue volume irradiated by tangential fields (p = 0.01), and administration of a boost (p = 0.005). High BMI (≥30 kg/m 2 ) (p = 0.0004) and boost (p = 0.02) were predictive of edema. A dose of 50 Gy/25 (p<0.0001) and a high irradiated tissue volume (p = 0.0001) were predictive of desquamation. A dose of 50 Gy/25 (p = 0.0005) and high BMI (p = 0.02) were predictors of pain. Bolus use was the only factor associated with bleeding (p = 0.02). Patients who developed desquamation were likely to receive corticosteroids/antihistamines (p<0.0001), topical antibiotics/antifungals (p<0.001), and dressings (p<0.0001)., Conclusion: The findings of this study provide evidence of potential predictors of RD and methods of symptom management based on symptom severity. Prevention of RD is needed among high-risk groups, such as patients with a high BMI or receiving a standard fractionation, boost, or bolus., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: Patients are commonly enrolled into clinical trials. It has been reported that these patients may have better outcomes than those not enrolled into the study. The reasoning from these improvements could be attributable to closer follow-up, better patient adherence, more health aware patients have, or reaction to observation such as the Hawthorne effect., Methods: Three hundred forty-six patients were approached for a prospective skin toxicity study in adjuvant breast cancer radiotherapy (RT) but declined participation between January 2018 and July 2019 (non-trial group). They were retrospectively reviewed and patient, treatment and RT-related characteristics, as well as the occurrence of skin reactions, and the usage of topical treatments were collected. This was compared with a comparison cohort of 349 patients who were enrolled into a previously conducted prospective study (trial group)., Results: More patients in the trial group had conventional RT (CFRT) versus hypofractionated RT (HFRT). Data was further stratified and there was no significant difference in moist desquamation, topical antibiotic usage, dressing application, home care use, topical corticoid steroid use, and oral analgesic use. There was a significantly lower pain score in the group compared with the non-trial group in both HFRT and CFRT (OR = 0.091 and OR = 0.348, p < 0.0001)., Conclusion: Our results demonstrated no differences other than pain between the trial group and non-trial group. Therefore, in this cohort, patients enrolled into an observational trial while undergoing adjuvant breast RT demonstrated similar experiences of skin reactions. There are challenges to assessing differences between these groups, as confounding is likely. Therefore, it is recommended for future studies to additionally assess the impact of study participation on outcomes such as quality of life, quality of care received, and/or anxiety levels.

Purpose: Stereotactic body radiation therapy (SBRT) for de novo (previously untreated) head and neck cancers (HNCs) is increasingly being used in medically unfit patients. A systematic review of SBRT was conducted for previously untreated HNCs., Methods and Materials: Medline (PubMed), excerpta medica database, and Cochrane Library databases were queried from inception until July 2020. Comparative outcome data were extracted where available up to 5 years. Results from random-effect models were presented in forest plots, with between-study heterogeneity evaluated by I 2 statistics and Q-tests., Results: Nine studies met inclusion criteria, representing 157 patients. Local control rates at 1, 2, and 3 years were as follows: 90.7% (95% confidence interval, 80.6%-95.6%), 81.8% (67.2%-90.7%), and 73.5% (40.4%-90.5%), respectively. Overall survival at 1, 2, and 3 years was 75.9% (75.1%-76.6%), 61.1% (60.3%-61.9%), and 50.0% (48.8%-51.4%), respectively. Late grade 3 to 4 toxicity rate was 3.3% (0.2%-10.2%), and late grade 5 toxicity rate was 0.1% (0.0%-1.0%)., Conclusions: SBRT for de novo HNC is safe and effective in providing locoregional control, with acceptable toxicities in most subsites. This finding warrants broader validation to guide its scope., (© 2020 The Author(s).)

Background: Oral health is important to general health but use of dental services varies considerably, particularly for children., Aims: We aimed to determine factors associated with parents' use of dental services for their children in Lebanon, and their perception of dental care relative to medical care., Methods: A convenience sample of public and private schools in Beirut was selected between January and May 2013. Parents of children in grades 2-6 (aged 7-12 years) were invited to complete a questionnaire covering socioeconomic characteristics and use of dental services. Logistic regression analysis was used to assess the relationship between use of dental services, and parents' socioeconomic characteristics and awareness and perceptions of dental services., Results: The parents of 316 children returned the questionnaire. Most children (72.8%) had been taken to the dentist in the past year, mainly for emergency care. Most parents (78.2%) considered dental care as important as or more important than medical care, and 89.9% were willing to contribute to dental insurance. Use of dental services was significantly associated with: older age of the parent (odds ratio, OR = 1.04; 95% confidence interval, CI: 1.02-1.06); awareness of dental care centres offering affordable treatment (OR = 3.18; 95% CI: 1.52-6.68); and children being in private schools (OR = 2.00, 95% CI: 1.08-3.95). It was negatively associated with > 4 children in the family compared with 1 child (OR = 0.18; 95% CI: 0.04-0.81)., Conclusion: Barriers to dental care for children were mostly related to economic factors., (Copyright © World Health Organization (WHO) 2020. Open Access. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Background: The adoption of hypofractionated radiotherapy (HFRT) into clinical practice varies widely despite randomized trials and guidelines supporting its equivalence to conventional fractionated radiotherapy (CFRT) for certain patient populations. We assessed the use of HFRT at a single institution from 2011 to 2018, as well as time-savings calculations., Patients and Methods: A retrospective cohort study was conducted for patients with breast cancer receiving adjuvant radiotherapy by HFRT or CFRT. Trends in HFRT use (≤ 16 fractions) were stratified according to 4 subgroups: tangential breast RT, locoregional breast RT, tangential chest wall RT, and locoregional chest wall RT. Treatment time savings were approximated using the institutional median treatment time., Results: A total of 5190 patients were included. HFRT use in all subgroups increased from 2011 to 2018. Tangential breast HFRT alone increased from 62.2% in 2011 to 96.9% in 2018. Locoregional breast HFRT and tangential chest wall HFRT use increased from less than 10% in 2011 to 76.2% and 76.9% in 2018. In locoregional chest wall RT, HFRT use of 44.9% was observed in 2018. Increased use of locoregional HFRT was mainly due to institutional policy changes. Time-savings calculations showed that 4002 hours of treatment or an additional 1402 HFRT courses could have been administered if all patients received HFRT., Conclusion: The use of HFRT at our center increased in all patient subgroups. More evidence and guidelines for patients receiving chest wall or locoregional HFRT are required because the use of HFRT remains low in these patient cohorts., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: We investigated quantitative ultrasound (QUS) in patients with node-positive head and neck malignancies for monitoring responses to radical radiotherapy (RT)., Materials & Methods: QUS spectral and texture parameters were acquired from metastatic lymph nodes 24 h, 1 and 4 weeks after starting RT. K-nearest neighbor and naive-Bayes machine-learning classifiers were used to build prediction models for each time point. Response was detected after 3 months of RT, and patients were classified into complete and partial responders., Results: Single-feature naive-Bayes classification performed best with a prediction accuracy of 80, 86 and 85% at 24 h, week 1 and 4, respectively., Conclusion: QUS-radiomics can predict RT response at 3 months as early as 24 h with reasonable accuracy, which further improves into 1 week of treatment., Competing Interests: Financial & competing interests disclosure This research was supported by Terry Fox Foundation Program Project Grant from the Hecht Foundation (Grant number 1083). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2020 Gregory J Czarnota.)

Background: In postmastectomy radiation therapy (PMRT), some centres prescribe the use of a tissue-equivalent bolus to the skin to reduce the risk of chest wall recurrence. The addition of bolus causes an increase in the skin dose, which may lead to increased risk of radiodermatitis. Radiodermatitis can decrease patients' overall quality of life, bringing into question the benefit of using the bolus. The purpose of this retrospective chart review was to quantify the increase in skin dose associated with the use of bolus in the PMRT setting., Materials and Methods: We evaluated 70 patients who underwent PMRT at our institution during 2012-2018. Two similar treatment plans were generated for each patient: one with bolus and one without. Skin dose-volume histogram values were evaluated, and statistical analysis was performed using MATLAB R2015b., Results: There was no significant difference in the maximum skin dose within a depth of 5 mm for bolus versus nonbolus plans (P = 0.4). However, within a depth of 3 mm, bolus plans had a maximum skin dose 7% ± 2.5% higher than the nonbolus plans (P < .00001). Mean skin dose within depths of 3 and 5 mm were both significantly higher (P < .00001) for bolus plans. The photon beam energy and chest wall separation showed minimal or no effect on skin dose., Conclusion: Given the differing opinions in the literature regarding the role for bolus in PMRT, there is still uncertainty of the optimal treatment method. This retrospective study demonstrates a 20%-30% reduction in mean skin dose when bolus is not used., (Copyright © 2020. Published by Elsevier Inc.)

Background: A single institutional experience of stereotactic body radiation therapy (SBRT) to medically unfit patients with unresectable head and neck cancers (HNCs)., Methods: A retrospective review of HNC patients undergoing SBRT was undertaken from 2011 to 2016 for fractionation ranges between 35 and 50 Gy in 4 to 6 fractions., Results: One hundred and fourteen patients with 117 SBRT courses were included with mean follow-up of 10.5 months. The cohort consisted of previously untreated primary HNC (n = 48), recurrent never irradiated HNC (n = 19), oligometastatic (n = 17) non-HNC primaries and previously irradiated HNC (n = 33). Local control (LC) at 12 months and median progression free survival was 85.8%, 78.2%, 85%, 78.9% (P = .86) and 23.7, 14.8, 10.5 and 7.8 months (P = .04) respectively. Only one patient had an acute grade 4 toxicity, two patients had grade 4 late toxicities., Conclusions: HNC SBRT is an effective treatment for frail patients where longer LC is relevant but are unable to tolerate protracted radiation schedules., (© 2020 Wiley Periodicals, Inc.)

Background: Local response prediction for brain metastases (BM) after stereotactic radiosurgery (SRS) is challenging, particularly for smaller BM, as existing criteria are based solely on unidimensional measurements. This investigation sought to determine whether radiomic features provide additional value to routinely available clinical and dosimetric variables to predict local recurrence following SRS., Methods: Analyzed were 408 BM in 87 patients treated with SRS. A total of 440 radiomic features were extracted from the tumor core and the peritumoral regions, using the baseline pretreatment volumetric post-contrast T1 (T1c) and volumetric T2 fluid-attenuated inversion recovery (FLAIR) MRI sequences. Local tumor progression was determined based on Response Assessment in Neuro-Oncology‒BM criteria, with a maximum axial diameter growth of >20% on the follow-up T1c indicating local failure. The top radiomic features were determined based on resampled random forest (RF) feature importance. An RF classifier was trained using each set of features and evaluated using the area under the receiver operating characteristic curve (AUC)., Results: The addition of any one of the top 10 radiomic features to the set of clinical features resulted in a statistically significant (P < 0.001) increase in the AUC. An optimized combination of radiomic and clinical features resulted in a 19% higher resampled AUC (mean = 0.793; 95% CI = 0.792-0.795) than clinical features alone (0.669, 0.668-0.671)., Conclusions: The increase in AUC of the RF classifier, after incorporating radiomic features, suggests that quantitative characterization of tumor appearance on pretreatment T1c and FLAIR adds value to known clinical and dosimetric variables for predicting local failure., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Metastasis to the gastrostomy site in patients with upper aerodigestive tract (UADT) malignancies is a rare but devastating adverse event that has been poorly described. Our aim was to determine the overall incidence and clinicopathologic characteristics observed with development of gastrostomy site metastasis in patients with UADT cancers., Methods: This was a systematic review and meta-analysis of 6138 studies retrieved from Medline, EMBASE, CINAHL, and the Cochrane Register after being queried for studies including gastrostomy site metastasis in patients with UADT malignancies., Results: The final analysis included 121 studies. Pooled analysis showed an overall event rate gastrostomy site metastasis of .5% (95% confidence interval [CI], .4%-.7%). Subgroup analysis showed an event rate of .56% (95% CI, .40%-.79%) with the pull technique and .29% (95% CI, .15%-.55%) with the push technique. Clinicopathologic characteristics observed with gastrostomy site metastasis were late-stage disease (T3/T4) (57.8%), positive lymph node status (51.2%), and no evidence of systemic disease (M0) (62.8%) at initial presentation. The average time from gastrostomy placement to diagnosis of metastasis was 7.78 ± 4.9 months, average tumor size on detection was 4.65 cm (standard deviation, 2.02), and average length of survival was 7.26 months (standard deviation, 6.23)., Conclusions: Gastrostomy site metastasis is a rare but serious adverse event that occurs at an overall rate of .5%, particularly in patients with advanced-stage disease, and is observed with a very poor prognosis. These findings emphasize a need for clinical practice guidelines to include a regular assessment of the PEG site and highlight the importance of detection and management of gastrostomy site metastasis by the multidisciplinary care oncology team., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. All rights reserved.)

Background: The influence of cigarette smoking on cancer risk has been well-studied. Similarly, exposure to ionizing radiation from radiotherapy (RT) can produce detrimental effects on an individual's health. In patients administered RT, there has been an observed relationship in other primary carcinomas. The purpose of this systematic review was to summarize the influence of cigarette smoking on outcomes post adjuvant RT in breast cancer patients., Methods: OVID Medline, Cochrane and Embase were searched and 1893 articles were identified. A total of 71 articles were included in the review. Study type, published year and sample size, age, systemic therapies, RT techniques and treatment side effects were collected if available., Results: The review found 198 different outcomes which fell into 7 categories and similar outcomes were recorded. 40% of skin reaction outcomes, 50% of cardiovascular outcomes, 71% of reconstruction outcomes, 29% of pulmonary function outcomes, 33% of mortality outcomes and 42% of secondary recurrence outcomes reported significant differences between smokers and non-smokers. None of the articles reported non-smokers to have a higher risk than smokers., Conclusion: Cigarette smoking can pose a higher risk of post-treatment complications that can influence an individual's quality of life, survival rate and/or recurrence risk. This review further assessed the impact of smoking on various patient outcomes and side-effects in the adjuvant breast RT setting. The information provided in this review suggest that smoking cessation programs would help educate patients to understand their risks of being a current or former smoker when undergoing RT., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: Head and neck cancer (HNC) and its treatment affects quality of life, with significant symptom burden. The main objectives of this study were to examine symptom trajectories of HNC patients by treatment and to identify factors associated with high ESAS scores., Methods and Materials: We conducted a retrospective cohort study in patients diagnosed with HNC in Ontario, Canada from 2007 to 2015 using linked health administrative databases. The primary outcome was a monthly patient self-reported moderate-to-severe (≥4) symptom score in the year following diagnosis. Multivariable Modified Poisson regression analyses with robust variance were used to investigate factors associated with moderate-to-severe scores., Results: Of 13,827 HNC patients identified, 4793 had ≥1 ESAS assessment within 12 months of cancer diagnosis. Overall, 60% (n = 2708) and 65% (n = 2903) of patients reported moderate-to-severe pain and poor appetite, respectively. The proportion of patients reporting a score ≥4 increased significantly during treatment and was most pronounced for those who received chemoradiation (CRT). On multivariable analysis, patients who were female (Relative Risk (RR) 1.15, 95% CI 1.08-1.23, received CRT, had a higher comorbidity burden (RR 1.31, 1.23-1.39), and had a diagnosis of oropharyngeal (1.10, 1.02-1.19), or oral cavity cancer (1.31, 1.19-1.45), were at an increased risk of reporting severe pain scores (p < 0.01 for all)., Conclusion: The majority of HNC patients report high pain scores, with symptom burden highest during the treatment phase, and especially for patients who received radiation or chemoradiation. This large study highlights the need for proactive symptom management during the HNC patients' cancer journey., (Copyright © 2019. Published by Elsevier Ltd.)

Aim: We aimed to identify quantitative ultrasound (QUS)-radiomic markers to predict radiotherapy response in metastatic lymph nodes of head and neck cancer., Materials & Methods: Node-positive head and neck cancer patients underwent pretreatment QUS imaging of their metastatic lymph nodes. Imaging features were extracted using the QUS spectral form, and second-order texture parameters. Machine-learning classifiers were used for predictive modeling, which included a logistic regression, naive Bayes, and k -nearest neighbor classifiers., Results: There was a statistically significant difference in the pretreatment QUS-radiomic parameters between radiological complete responders versus partial responders (p < 0.05). The univariable model that demonstrated the greatest classification accuracy included: spectral intercept (SI)-contrast (area under the curve = 0.741). Multivariable models were also computed and showed that the SI-contrast + SI-homogeneity demonstrated an area under the curve = 0.870. The three-feature model demonstrated that the spectral slope-correlation + SI-contrast + SI-homogeneity-predicted response with accuracy of 87.5%., Conclusion: Multivariable QUS-radiomic features of metastatic lymph nodes can predict treatment response a priori ., Competing Interests: Financial & competing interests disclosure This project was funded in part, by the Terry Fox Research Institute (Terry Fox New Frontiers Program Project Grant), the Hecht Foundation, and the Kavelman-Fonn Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2019 Gregory J Czarnota.)

Purpose: Magnetic resonance imaging (MRI) is the primary modality for targeting brain tumors in radiotherapy treatment planning (RTP). MRI is not directly used for dose calculation since image voxel intensities of MRI are not associated with EDs of tissues as those of computed tomography (CT). The purpose of the present study is to develop and evaluate a tissue segmentation-based method to generate a synthetic-CT (sCT) by mapping EDs to corresponding tissues using only T1-weighted MR images for MR-only RTP., Methods: Air regions were contoured in several slices. Then, air, bone, brain, cerebrospinal fluid (CSF), and other soft tissues were automatically segmented with an in-house algorithm based on edge detection and anatomical information and relative intensity distribution. The intensities of voxels in each segmented tissue were mapped into their CT number range to generate a sCT. Twenty-five stereotactic radiosurgery and stereotactic ablative radiotherapy patients' T1-weighted MRI and coregistered CT images from two centers were retrospectively evaluated. The CT was used as ground truth. Distances between bone contours of the external skull of sCT and CT were measured. The mean error (ME) and mean absolute error (MAE) of electron density represented by standardized CT number was calculated in HU., Results: The average distance between the contour of the external skull in sCT and the contour in coregistered CT is 1.0 ± 0.2 mm (mean ± 1SD). The ME and MAE differences for air, soft tissue and whole body voxels within external body contours are -4 HU/24 HU, 2 HU/26 HU, and -2 HU/125 HU, respectively., Conclusions: A MR-sCT generation technique was developed based on tissue segmentation and voxel-based tissue ED mapping. The generated sCT is comparable to real CT in terms of anatomical position of tissues and similarity to the ED assignment. This method provides a feasible method to generate sCT for MR-only radiotherapy treatment planning., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: To evaluate standardized uptake value (SUV) stability on pretreatment and intratreatment 18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in patients undergoing definitive CRT for head and neck cancer (HNC)., Methods: Primary tumor and nodal volumes of interest (VOIs) from HNC patients were contoured on the pretreatment and intratreatment PET-CT by two independent observers. SUV stability was measured with intersection calculations (DICE, overlap fraction, center to center) between the VOIs at threshold levels of 50%, 60%, 70%, 80%, and 90% of the SUV maximum., Results: The mean calculated DICE of the 50%, 60%, 70%, 80%, 90% SUV threshold was 0.53, 0.48, 0.41, 0.28, and 0.12, respectively. The mean calculated overlap fraction was 0.71, 0.65, 0.58, 0.43, and 0.2, respectively. Center-center difference demonstrates spatial variability of 7.8, 8.2, 8.6, 9.5, and 11.2 mm for these SUV subvolumes of interest., Conclusions: HNC subvolumes defined by SUV thresholding technique in FDG PET-CT imaging do not remain physically stable during (chemo)RT., Highlights: All pretreatment and intratreatment SUV thresholds (50%-90%) overlap indexes are low during the course of (chemo)radiation. Pretreatment and intratreatment center to center variation further corroborates that all FDG threshold volumes do not remain stable during treatment. No difference in SUV threshold stability was seen between p16 positive and negative tumors., (© 2019 Wiley Periodicals, Inc.)

Background: Management of locally-advanced breast cancer is determined by multiple factors, but in patients without distant metastases often involves neoadjuvant systemic therapy, surgery and radiation. If the primary tumour remains unresectable following systemic therapy, radiotherapy may be used for tumour shrinkage prior to surgery. When metastatic disease is present, locoregional radiotherapy is generally reserved for management of tumour-related symptoms. We reviewed our experience of high-dose radiotherapy for unresected locally-advanced breast cancer., Methods: A retrospective chart review was conducted of patients with unresected locally advanced breast cancer (LABC) receiving external beam radiotherapy to the breast, chest wall and/or regional lymph nodes. Patients were stratified based on the presence of metastatic disease at presentation. Patient demographics, disease characteristics, and treatment outcomes were recorded., Results: Forty-three cases were analyzed between 2004 and 2016. Median follow-up was 25 months from diagnosis and 14 months from completion of radiotherapy. There were 24 cases (56%) with metastatic disease on presentation, and 19 (44%) without. Tumour shrinkage occurred within 3 months of completing radiotherapy in 36 cases (84%). Ulceration and bleeding improved following radiotherapy in 13 (54%) of the 24 applicable cases. Twenty-six patients (60%) developed moist desquamation but none experienced grade 4 or 5 radiation dermatitis. Median locoregional progression-free survival for all patients was 12 months from completion of radiotherapy. Locoregional progression-free survival (P=0.2) and overall survival (OS) (P=0.4) were not significantly different between patients with and without distant metastases at presentation., Conclusions: Radiotherapy provided good response and symptom control in most patients in this study; there is a role for palliative radiotherapy in patients with LABC.

Background: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient's plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC)., Methods: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT., Discussion: Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC., Trial Registration: ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.

Purpose: Modern linear accelerators are equipped with cone beam computed tomography and robotic couches that can correct for errors in the translational (X, Y, Z) and rotational (α, β, γ) axes prior to treatment delivery. Here, we compared the positional accuracy of 2 cone beam registration approaches: (1) employing translational shifts only in 3 degrees of freedom (X, Y, Z), versus; (2) using translational-rotational shifts in 6 degrees of freedom (X, Y, Z, α, β, γ)., Methods: This retrospective study examined 140 interfraction cone beam images from 20 patients with head and neck cancer treated with standard intensity-modulated radiation therapy. The cone beam images were matched to planning simulation scans in 3, then in 6 degrees of freedom, using the mandible, clivus, and C2 and C7 vertebrae as surrogate volumes. Statistical analyses included a generalized mixed model and was used to assess whether there were significant differences in acceptable registrations between the 2 correction methods., Results: The rates of improvement with corrections in 6 degrees of freedom for the mandible with a 5-mm expansion margin were 54.55% ( P = .793), for the clivus 85.71% ( P = .222), and for C7 87.50% ( P = .015). There was a 100% increase in acceptability for the C2 vertebra within the 5-mm margin ( P < .001). For the 3-mm expansion margin, the rates of improvement for the mandible, clivus, C2, and C7 were 63.16% ( P = .070), 91.30% ( P = .011), 84.21% ( P = .027), and 76.92% ( P < .001), respectively., Conclusions: Significant registration improvements with the use of rotational corrections with a 5-mm expansion margin are only seen in the C7 vertebra. At the 3-mm margin, significant improvements are found for the C2, C7, and clivus registrations, suggesting that intensity-modulated radiotherapy treatments for head and neck cancers with 3-mm planning target volume margins may benefit from corrections in 6 degrees of freedom.

The main objective of this study was to investigate the ameliorative effects of aspirin eugenol ester (AEE) in hyperlipidemic rat. After five-week oral administration of AEE in high fat diet (HFD)-induced hyperlipidemic rats, the impact of AEE on plasma and urine metabonomics was investigated to explore the underlying mechanism by UPLC-Q-TOF/MS analysis. Blood lipid levels and histopathological changes of liver, stomach and duodenum were also evaluated after AEE treatment. Without obvious gastrointestinal (GI) side effects, AEE significantly relieved fatty degeneration of liver and reduced triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TCH) (P<0.01). Clear separations of metabolic profiles were observed among control, model and AEE groups by using principal component analysis (PCA) and orthogonal partial least-squares-discriminate analysis (OPLS-DA). 16 endogenous metabolites in plasma and 18 endogenous metabolites in urine involved in glycerophospholipid metabolism, fatty acid metabolism, fatty acid beta-oxidation, amino acid metabolism, TCA cycle, sphingolipid metabolism, gut microflora and pyrimidine metabolism were considered as potential biomarkers of hyperlipidemia and be regulated by AEE administration. It might be concluded that AEE was a promising drug candidate for hyperlipidemia treatment. These findings could contribute to the understanding of action mechanisms of AEE and provide evidence for further studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The HexaPOD has been developed to correct for errors in six degrees of freedom (6DOF), which enables it with the potential to improve setup accuracy. This is critical in hypofractionated head and neck (H&N) stereotactic body radiation therapy (SBRT) plans, which have highly conformal dose distributions and close proximity of critical normal structures., Purpose: The purpose of the study was to investigate whether using the HexaPOD to correct for error in 6DOF will increase setup accuracy for H&N SBRT patients., Methods and Materials: For each of the 20 SBRT H&N patients in this study, two sets of global computed tomography scans and cone beam computed tomography matches were performed for the first and last fraction of each patient's treatment. One of the global matches included corrections for rotations and the other did not. Next, sub-regions of interest, based on bony landmarks, were identified for each patient and local registrations were performed to match these sub-regions of interest to determine local sub-region errors in the global registration. The differences in local error, with and without rotations, were examined to determine whether the residual local setup errors were significantly different., Results: T-test results demonstrate a statistically significant difference in local error when correcting for rotations vs. not, in all 6DOF. When examining the actual magnitude of residual error reduction using three-dimensional vectors of the average translational differences, an average reduction of 0.9 mm is observed when 6DOF corrections are applied., Conclusions: Residual setup errors in each of the 6DOF were statistically significant; however, the magnitude depicts a very small reduction in residual error <1 mm. Clinically, this makes a very small difference because the planning target volume (PTV) presumably covers an expansion of 3-5 mm., (Copyright © 2017 Canadian Association of Medical Radiation Technologists. Published by Elsevier Inc. All rights reserved.)

Aim: To provide a multi-institutional description of current practices of stereotactic body radiotherapy (SBRT) for head and neck cancer., Materials & Methods: 15 international institutions with significant experience in head and neck SBRT were asked to complete a questionnaire covering clinical and technical factors., Results: SBRT is used 10-100% of the time for recurrent primary head and neck cancer, and 0-10% of the time in newly diagnosed disease. Five centers use a constraint for primary disease of 3-5 cm and 25-30 cc. Nine institutions apply a clinical target volume expansion of 1-10 mm and 14 use a planning target volume margin of 1-5 mm. Fractionation regimens vary between 15 and 22 Gy in 1 fraction to 30-50 Gy in 5 or 6 fractions. The risk of carotid blowout quoted in the re-irradiation setting ranges from 3 to 20%., Conclusion: There is considerable heterogeneity in patient selection and techniques in head and neck SBRT practice among experienced centers.

Background: Aspirin and eugenol were esterified to synthesize aspirin eugenol ester (AEE). As a pale yellow and odourless crystal, AEE reduced the gastrointestinal damage of aspirin and vulnerability of eugenol. The study was conducted to evaluate the preventive effects of AEE on blood lipids in rats with high fat diet (HFD)., Methods: Suspensions of AEE and simvastatin were prepared in 5% carboxymethyl cellulose sodium (CMC-Na). In order to observe the intervention effects, the drugs and HFD were administrated at the same time. Based on individual weekly body weight (BW), AEE was intragastrically administrated at the dosage of 18, 36 and 54 mg/kg. Simvastatin (10 mg/kg) and CMC-Na (20 mg/kg) were used as control drug. After 6 weeks of administration, the changes of BW and blood lipid indices including triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol (TCH) were determined in the experiment., Results: The rat blood lipids profile in model group was remarkably different after feeding 6-weeks HFD. TG, TCH and LDL indexes in model group were increased significantly compared with those in control group (p < 0.01). AEE at the dosage of 54 mg/kg significantly decreased levels of TG, TCH and LDL (p < 0.01), and slowed the rate of BW gain in comparison with model group (p < 0.05). Moreover, high dose AEE showed better effects than simvastatin on reducing TCH level and similar effects on TG, HDL and LDL., Conclusion: AEE could remarkably reduce levels of TG, TCH and LDL in rats with high fat diet, and slow the rate of body weight gain. It was conducted that AEE was a potential candidate on reducing blood lipids level. The mechanism of action of AEE should be investigated in further studies.

Cardiovascular disease (CVD) is a global epidemic, which is largely preventable. Cardiac rehabilitation (CR) is demonstrated to be efficacious and cost-effective for secondary prevention in high-income countries. Given its affordability, CR should be more broadly implemented in middle-income countries as well. Hence, the International Council of Cardiovascular Prevention and Rehabilitation (ICCPR) convened a writing panel to recommend strategies to deliver all core CR components in low-resource settings, namely: (1) initial assessment, (2) lifestyle risk factor management (i.e., diet, tobacco, mental health), (3) medical risk factor management (lipids, blood pressure), (4) education for self-management; (5) return to work; and (6) outcome evaluation. Approaches to delivering these components in alternative, arguably lower-cost settings, such as the home, community and primary care, are provided. Recommendations on delivering each of these components where the most-responsible CR provider is a non-physician, such as an allied healthcare professional or community health care worker, are also provided., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Cardiovascular disease is a global epidemic, which is largely preventable. Cardiac rehabilitation (CR) is demonstrated to be cost-effective and efficacious in high-income countries. CR could represent an important approach to mitigate the epidemic of cardiovascular disease in lower-resource settings. The purpose of this consensus statement was to review low-cost approaches to delivering the core components of CR, to propose a testable model of CR which could feasibly be delivered in middle-income countries., Methods: A literature review regarding delivery of each core CR component, namely: (1) lifestyle risk factor management (ie, physical activity, diet, tobacco and mental health), (2) medical risk factor management (eg, lipid control, blood pressure control), (3) education for self-management and (4) return to work, in low-resource settings was undertaken. Recommendations were developed based on identified articles, using a modified GRADE approach where evidence in a low-resource setting was available, or consensus where evidence was not., Results: Available data on cost of CR delivery in low-resource settings suggests it is not feasible to deliver CR in low-resource settings as is delivered in high-resource ones. Strategies which can be implemented to deliver all of the core CR components in low-resource settings were summarised in practice recommendations, and approaches to patient assessment proffered. It is suggested that CR be adapted by delivery by non-physician healthcare workers, in non-clinical settings., Conclusions: Advocacy to achieve political commitment for broad delivery of adapted CR services in low-resource settings is needed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)