Mild hyperthermia with magnetic resonance- guided high intensity focused ultrasound combined with salvage chemoradiation for recurrent rectal cancer.

INTRODUCTION: Pelvic recurrences from rectal cancer present a challenging clinical scenario. Hyperthermia represents an innovative treatment option in combination with concurrent chemoradiation to enhance therapeutic effect. We provide the initial results of a prospective single center feasibility study (NCT02528175) for patients undergoing rectal cancer retreatment using concurrent chemoradiation and mild hyperthermia with MR-guided high intensity focused ultrasound (MR-HIFU). METHODS: All patients were deemed ineligible for salvage surgery and were evaluated in a multidisciplinary fashion with a surgical oncologist, radiation oncologist and medical oncologist. Radiation was delivered to a dose of 30.6 Gy in 1.8 Gy per fraction with concurrent capecitabine. MR-HIFU was delivered on days 1, 8 and 15 of concurrent chemoradiation. Our primary objective was feasibility and toxicity. RESULTS: Six patients (total 11 screened) were treated with concurrent chemoradiation and mild hyperthermia with MR-HIFU. Tumor size varied between 3.1-16.6 cm. Patients spent an average of 228 min in the MRI suite and sonication with the external transducer lasted an average of 35 min. There were no complications on the day of the MR-HIFU procedure and all acute toxicities (no grade >/=3 toxicities) resolved after completion of treatment. There were no late grade >/=3 toxicities. CONCLUSION: Mild hyperthermia with MR-HIFU, in combination with concurrent chemoradiation for appropriately selected patients, is safe for localized pelvic recurrences from rectal cancer. The potential for MR-HIFU to be applied in the recurrent setting in rectal cancer treatment requires further technical development and prospective evaluation.

Radiation myelopathy following stereotactic body radiation therapy for spine metastases.

PURPOSE: Stereotactic body radiation therapy (SBRT) is now considered a standard of care treatment option in the management of spine metastases. One of the most feared complications of spine SBRT is radiation myelopathy (RM). METHODS: We provided a narrative review of RM following spine SBRT based on review of the published literature, including data on spinal cord dose constraints associated with the risk of RM, strategies to mitigate the risk, and management options for RM. RESULTS: There are limited published data of cases of RM following spine SBRT with detailed spinal cord dosimetry. The HyTEC report provided recommendations for the point maximal dose (Dmax) for the spinal cord that is associated with a < 5% risk of RM for 1-5 fractions spine SBRT. In the setting of spine SBRT reirradiation after previous conventional external beam radiation therapy (cEBRT), factors associated with RM are: SBRT spinal cord Dmax, cumulative spinal cord Dmax, and the time interval between previous RT and SBRT reirradiation. There are various strategies to mitigate the risk of RM, including accurate delineation of the spinal cord (or thecal sac), strict adherence to the recommended spinal cord dose constraints, and robust treatment immobilisation set-up and delivery. Limited effective treatment options are available for patients who develop RM, and these include corticosteroids, hyperbaric oxygen, and bevacizumab; however, none have been supported by high quality evidence. CONCLUSION: RM is a rare but devastating complication following SBRT for spine metastases. There are strategies to minimise the risk of RM to ensure safe delivery of spine SBRT.

Crisis management research (1985-2020) in the hospitality and tourism industry: A review and research agenda.

The global tourism industry has already suffered an enormous loss due to COVID-19 (Coronavirus Disease 2019) in 2020. Crisis management, including disaster management and risk management, has been becoming a hot topic for organisations in the hospitality and tourism industry. This study aims to investigate relevant research domains in the hospitality and tourism industry context. To understand how crisis management practices have been adopted in the industry, the authors reviewed 512 articles including 79 papers on COVID-19, spanning 36 years, between 1985 and 2020. The findings showed that the research focus of crisis management, crisis impact and recovery, as well as risk management, risk perception and disaster management dominated mainstream crisis management research. Look back the past decade (2010 to present), health-related crisis (including COVID-19), social media, political disturbances and terrorism themes are the biggest trends. This paper proposed a new conceptual framework for future research agenda of crisis management in the hospitality and tourism industry. Besides, ten possible further research areas were also suggested in a TCM (theory-context-method) model: the theories of crisis prevention and preparedness, risk communication, crisis management education and training, risk assessment, and crisis events in the contexts of COVID-19, data privacy in hospitality and tourism, political-related crisis events, digital media, and alternative analytical methods and approaches. In addition, specific research questions in these future research areas were also presented in this paper.

Clinical and pathological characterization of FLNC-related myofibrillar myopathy caused by founder variant c.8129G>A in Hong Kong Chinese.

FLNC-related myofibrillar myopathy could manifest as autosomal dominant late-onset slowly progressive proximal muscle weakness; involvements of cardiac and/or respiratory functions are common. We describe 34 patients in nine families of FLNC-related myofibrillar myopathy in Hong Kong ethnic Chinese diagnosed over the last 12 years, in whom the same pathogenic variant c.8129G>A (p.Trp2710*) was detected. Twenty-six patients were symptomatic when diagnosed; four patients died of pneumonia and/or respiratory failure. Abnormal amorphous material or granulofilamentous masses were detected in half of the cases, with mitochondrial abnormalities noted in two-thirds. We also show by haplotype analysis the founder effect associated with this Hong Kong variant, which might have occurred 42 to 71 generations ago or around Tang and Song dynasties, and underlain a higher incidence of myofibrillar myopathy among Hong Kong Chinese. The late-onset nature and slowly progressive course of the highly penetrant condition could have significant impact on the family members, and an early diagnosis could benefit the whole family. Considering another neighboring founder variant in FLNC in German patients, we advocate development of specific therapies such as chaperone-based or antisense oligonucleotide strategies for this particular type of myopathy.

Mapping the contribution and strategic distribution patterns of neuroimaging features of small vessel disease in poststroke cognitive impairment.

OBJECTIVES: Individual neuroimaging features of small vessel disease (SVD) have been reported to influence poststroke cognition. This study aimed to investigate the joint contribution and strategic distribution patterns of multiple types of SVD imaging features in poststroke cognitive impairment. METHODS: We studied 145 first-ever ischaemic stroke patients with MRI and Montreal Cognitive Assessment (MoCA) examined at baseline. The local burdens of acute ischaemic lesion (AIL), white matter hyperintensity, lacune, enlarged perivascular space and cross-sectional atrophy were quantified and entered into support vector regression (SVR) models to associate with the global and domain scores of MoCA. The SVR models were optimised with feature selection through 10-fold cross-validations. The contribution of SVD features to MoCA scores was measured by the prediction accuracy in the corresponding SVR model after optimisation. RESULTS: The combination of the neuroimaging features of SVD contributed much more to the MoCA deficits on top of AILs compared with individual SVD features, and the cognitive impact of different individual SVD features was generally similar. As identified by the optimal SVR models, the important SVD-affected regions were mainly located in the basal ganglia and white matter around it, although the specific regions varied for MoCA and its domains. CONCLUSIONS: Multiple types of SVD neuroimaging features jointly had a significant impact on global and domain cognitive functionings after stroke on top of AILs. The map of strategic cognitive-relevant regions of SVD features may help clinicians to understand their complementary impact on poststroke cognition.

Synchronous anal canal carcinoma in a heterosexual couple.

BACKGROUND: Sexually transmitted Human Papilloma Virus (HPV) infection is a known risk factor for cancer of the anal canal in both men and women. CASE PRESENTATION: We describe a report of synchronous carcinoma of the anal canal in a heterosexual couple. High risk type 16 HPV DNA was detected in both tumors. CONCLUSION: Longstanding sexual partners may share risk of HPV-associated anal canal cancer.

IKBB tumor suppressive role in nasopharyngeal carcinoma via NF-κB-mediated signalling.

Tumor suppressor genes (TSGs) play a prominent role in cancer and are important in the development of nasopharyngeal carcinoma (NPC), which is endemic in Southern China as well as Southeast Asia. Apart from TSGs, aberrant signalling pathways are also commonly associated with tumor progression. Unsurprisingly, the NF-κB pathway is frequently associated with angiogenesis and promoting tumor growth and development. Functional complementation studies using microcell-mediated chromosome transfer helped to identify IKBB as a putative TSG in NPC. IKBB, an inhibitor of NF-κB, has recently been shown to be inversely associated with tumor growth and metastasis via inactivation of the NF-κB pathway, but its suppressive role is still only poorly understood. This study takes the lead in revealing the suppressive role of IKBB in NPC. IKBB is silenced in the majority of NPC tumor tissues in all stages. Its suppressive role is substantiated by perturbation in tumor formation, cell migration and angiogenesis. Interestingly, IKBB not only affects the 'seed', but also influences the 'soil' by downregulating the transcriptional level of proangiogenic factors Rantes, Upar, IL6, and IL8. For the first time, our data establish the importance of a novel tumor suppressive IKBB gene in abrogating angiogenesis in NPC via the NF-κB signalling pathway, which is likely mediated by crosstalk with the Akt/Gsk3ß signalling pathway.

A novel prospective descriptive analysis of nausea and vomiting among patients receiving gastrointestinal radiation therapy.

PURPOSE: Nausea and vomiting are common side effects from radiotherapy that can interfere with gastrointestinal (GI) cancer patients' quality of life (QOL). This study described the subjective experience of patients with radiation-induced nausea and vomiting (RINV) and its relation to QOL. METHODS: Forty-eight patients treated with abdominal radiotherapy alone or with concomitant chemoradiotherapy were followed in a prospective study. All episodes of nausea, vomiting, and antiemetic use were recorded daily for the treatment period and the week following completion of therapy. QOL was assessed weekly using the Functional Living Index-Emesis QOL Tool (FLIE) and the EORTC QLQ-C30 core questionnaire (C30). RESULTS: In total, 351 episodes of nausea severity, duration, onset time, and 154 outcomes of vomiting onset times and contents were documented. The median nausea severity experienced per episode was 5 (on a scale from 1 to 10), and the most common durations of nausea were 30 min or less and constant nausea all day and night. The most common location of nausea was the abdomen. Longer nausea duration, great nausea severities, and the location of nausea experienced had significant adverse relationships to multiple QOL items on both the FLIE and the C30. In addition, the onset timing and number of vomiting episodes were related to the majority of all FLIE and QOL scores. CONCLUSION: Patient's subjective experiences of RINV directly correlated to the worsening of QOL outcomes. The identification and amelioration of these RINV experiences could improve QOL.

Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus.

Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53) gene but absence of Cdkn1a (p21) did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation.

The safety of allogeneic innate lymphocyte therapy for glioma patients with prior cranial irradiation.

The standard treatment of high-grade glioma presents a combination of radiotherapy, chemotherapy and surgery. Immunotherapy is proposed as a potential adjunct to standard cytotoxic regimens to target remaining microscopic disease following resection. We have shown ex vivo expanded/activated γδ T cells to be a promising innate lymphocyte therapy based on their recognition of stress antigens expressed on gliomas. However, successful integration of γδ T cell therapy protocols requires understanding the efficacy and safety of adoptively transferred immune cells in the post-treatment environment. The unique features of γδ T cell product and the environment (hypoxia, inflammation) can affect levels of expression of key cell receptors and secreted factors and either promote or hinder the feasibility of γδ T cell therapy. We investigated the potential for the γδ T cells to injure normal brain tissue that may have been stressed by treatment. We evaluated γδ T cell toxicity by assessing actual and correlative toxicity indicators in several available models including: (1) expression of stress markers on normal primary human astrocytes (as surrogate for brain parenchyma) after irradiation and temozolomide treatment, (2) cytotoxicity of γδ T cells on normal and irradiated primary astrocytes, (3) microglial activation and expression of stress-induced ligands in mouse brain after whole-brain irradiation and (4) expression of stress-induced markers on human brain tumors and on normal brain tissue. The lack of expression of stress-induced ligands in all tested models suggests that γδ T cell therapy is safe for brain tumor patients who undergo standard cytotoxic therapies.

Symptom clusters of gastrointestinal cancer patients undergoing radiotherapy using the Functional Living Index-Emesis (FLIE) quality-of-life tool.

OBJECTIVE: The Functional Living Index-Emesis (FLIE) instrument is a validated nausea and vomiting specific quality of life (QOL) tool originally created as a 3-day test of the impact of chemotherapy-induced nausea and vomiting on cancer patients' daily life. The primary objective of the present study was to retrospectively explore the use of the FLIE from data obtained in a previously published study of patients with gastrointestinal radiation-induced nausea and vomiting (RINV) and compare the extracted symptom clusters on a weekly basis for the entirety of gastrointestinal cancer patients' radiotherapy treatments. METHODS: QOL was assessed on a weekly basis using the 18-item FLIE questionnaire for patients' radiotherapy treatments. A principal component analysis with varimax rotation was performed at each visit. The internal consistency and reliability of the derived clusters was assessed with Cronbach's alpha. Robust relationship and correlation among symptoms was displayed with biplot graphics. RESULTS: A total of 460 FLIE assessments were completed for the 86 gastrointestinal patients who underwent radiotherapy. Two components were consistently identified except for week 5 where only one component was identified. Component 1 contained the items "Q10-Q18" which included all vomiting items. Component 2 included all nausea items from "Q1 to Q9". All the variables were well accounted for by two components for most weeks of treatment with excellent internal consistency. Biplots indicate that the two symptom clusters were evident at each week, with the exception of the first week of treatment. Strong correlations were seen between the effect of nausea on patients' ability to make meals, patients' ability to do tasks within the home, and patients' willingness to spend time with family and friends. CONCLUSION: The high internal consistency at all timepoints indicates that the FLIE QOL instrument is useful for the RINV population.

Tumor radiation response enhancement by acoustical stimulation of the vasculature.

We have discovered that ultrasound-mediated microbubble vascular disruption can enhance tumor responses to radiation in vivo. We demonstrate this effect using a human PC3 prostate cancer xenograft model. Results indicate a synergistic effect in vivo with combined single treatments of ultrasound-stimulated microbubble vascular perturbation and radiation inducing an over 10-fold greater cell kill with combined treatments. We further demonstrate with experiments in vivo that induction of ceramide-related endothelial cell apoptosis, leading to vascular disruption, is a causative mechanism. In vivo experiments with ultrasound and bubbles permit radiation doses to be decreased significantly for comparable effect. We envisage this unique combined ultrasound-based vascular perturbation and radiation treatment method being used to enhance the effects of radiation in a tumor, leading to greater tumor eradication.

Neuropathology of cigarette smoking.

It is well established that cigarette smoking is hazardous to health and is a risk factor for many chronic diseases. However, its impact on the brain, whether it be from prenatal exposure to maternal cigarette smoking, cerebrovascular disease, Alzheimer's disease (AD) or Parkinson's disease, is still not very clear. Neuroimaging and neuropathological investigations suggest that there are heterogeneous effects of cigarette smoking on the brain. On the one hand, it is quite clear that cigarette smoking causes damage to endothelial cells, resulting in increased risk of cerebrovascular disease. On the other hand, it seems to be associated with different Alzheimer's pathologies in post-mortem brains and experimental models, despite the fact that epidemiological studies clearly indicate a positive correlation between cigarette smoking and increased risk for AD. Interestingly, cigarette smoking appears to be associated with reduced Parkinson's pathology in post-mortem brains. However, although nicotine in cigarettes may have some neuroprotective actions, the effects of all the other toxic compounds in cigarettes cannot be ignored. It is, therefore, our aim to summarize what is known about the neuropathology of cigarette smoking and, in particular, its implications for neurodegenerative diseases.

A prospective study of gastrointestinal radiation therapy-induced nausea and vomiting.

OBJECTIVE: Nausea and vomiting are common side effects from radiotherapy that can interfere with gastrointestinal (GI) cancer patients' quality of life (QOL). A prospective study among patients with GI cancers was conducted to document the timing, incidence and risk factors of radiation therapy-induced nausea and vomiting (RINV). METHODS: Forty-eight patients planned to receive curative or palliative intent abdominal and/or pelvic radiotherapy alone or with concomitant chemoradiotherapy were followed prospectively. All episodes of nausea, vomiting, retching and antiemetic use were recorded daily for the entire treatment period and for the week following completion of therapy. QOL was assessed weekly using the Functional Living Index--Emesis Quality of Life Tool and the EORTC QLQ-C30 core questionnaire. RESULTS: Nausea occurred in 83 % of patients and emesis in 54 %. Pancreatic cancer was significantly correlated to higher proportions of nausea and emesis (p = 0.002 and p = 0.0003) compared to other primary sites. There were no significant difference between concomitant chemoradiotherapy and radiotherapy only patients for nausea and emesis. Patients had significantly greater proportions of RINV during the first, second and fifth weeks of treatment and during the first week following treatment. Vomiting was found to impair patients' usual recreation or leisure activities and enjoyment of their meals. Worse physical, role and social functioning and greater fatigue and appetite loss over the course of treatment correlated directly with the timing of RINV symptoms. CONCLUSION: RINV worsened QOL and was experienced even after treatment was completed; physicians should therefore be cognizant and monitor patients in the week following radiotherapy. Concomitant chemoradiotherapy should potentially be included in the moderate emetogenic risk category.

Depression, anxiety, and stress among university students in Selangor, Malaysia during COVID-19 pandemics and their associated factors.

INTRODUCTION: This study aims to assess the impacts of COVID-19 pandemics among university students in Malaysia, by identifying the prevalence of depression, anxiety and stress among them and their respective predictors. METHODOLOGY: An online cross-sectional study was conducted via non-probabilistic convenience sampling. Data were collected on sociodemographic characteristics, lifestyle, COVID-19 related influences. Mental health status was assessed with depression, anxiety, and stress scale (DASS-21). RESULTS: 388 students participated this study (72.4% female; 81.7% Bachelor's student). The prevalence of moderate to severe depression, anxiety and stress among university students are 53.9%, 66.2% and 44.6%, respectively. Multivariable logistic regression analysis found that the odds of depression were lower among students who exercise at least 3 times per week (OR: 0.380, 95% CI: 0.203-0.711). The odd ratio of student who had no personal history of depression to had depression, anxiety and stress during this pandemic was also lower in comparison (OR: 0.489, 95% CI: 0.249-0.962; OR: 0.482, 95% CI: 0.241-0.963; OR: 0.252, 95% CI: 0.111-0.576). Surprisingly, students whose are currently pursuing Master study was associated with lower stress levels (OR: 0.188, 95% CI: 0.053-0.663). However, student who had poorer satisfaction of current learning experience were more likely to experience stress (OR: 1.644, 95% CI: 1.010-2.675). LIMITATIONS: It is impossible to establish causal relationships between variables on mental health outcomes, and there is a risk of information bias. CONCLUSION: The prevalence of mental health issues among university students is high. These findings present essential pieces of predictive information when promoting related awareness among them.

Feasibility and safety of left distal trans-radial approach for coronary angiogram and percutaneous coronary intervention in a center in Hong Kong.

INTRODUCTION: The left distal trans-radial approach is not only more convenient for the operator than the conventional left forearm radial approach, it is also more comfortable for right-hand patients during the peri-procedural period. Comparing with conventional approach, it has lower bleeding risk, less pain and lower risk of radial artery occlusion. The aim of this study was to determine the feasibility and the safety of left distal trans-radial approach for coronary angiogram and percutaneous coronary intervention in Hong Kong Chinese who had smaller body built and therefore smaller radial arterial size. METHOD: In this single-center prospective study, 72 patients undergoing elective coronary angiography and/or percutaneous coronary intervention were recruited from August to October 2018. All right-handed patients aged 18 or above undergoing elective procedures during the period were recruited. Exclusion criteria were non-palpable radial arteries, pregnancies, incapability to consent, abnormal Allen's test, and emergency procedures. Sixty patients (42 males, age ranging from 45 to 86 years old) were recruited and underwent the procedures via left distal radial approach. The measurements during access establishment, the procedure details, complications, patients' satisfaction, and arterial occlusion rate were studied. RESULTS: The procedures with left distal radial approach were successful in 51 patients (85%). Crossover rate to conventional right radial approach was 15% (nine patients). Among successful cases, the mean patients' satisfaction was 8.32/10 and the mean pain score was 1.6/10. Post-procedural radial artery occlusion was not encountered. CONCLUSION: Left distal radial approach is a feasible alternative for patients undergoing coronary angiography and/or percutaneous coronary intervention in Hong Kong Chinese patients. It provides good comfortability with minimal pain in right-handed patients. The risk of radial artery occlusion is minimal.

International Validation of the EORTC QLQ-ANL27, a Field Study to Test the Anal Cancer-Specific Health-Related Quality-of-Life Questionnaire.

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27. METHODS AND MATERIALS: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated. RESULTS: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed. CONCLUSIONS: The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.

Prophylaxis of radiotherapy-induced nausea and vomiting in the palliative treatment of bone metastases.

PURPOSE: To document the incidence and timing of radiotherapy-induced nausea and vomiting (RINV) in the treatment of bone metastases among patients receiving prophylaxis with a 5-HT(3) receptor antagonist. METHODS: Patients receiving single (SF) or multiple fraction (MF) palliative radiotherapy (RT) of moderate or low emetogenic risk for bone metastases were prescribed prophylactic Ondansetron. The frequency and duration of prophylaxis and the use of rescue antiemetics were left to the discretion of the treating physicians. Patients documented episodes of nausea (N) and vomiting (V) in daily diaries before and during RT, and until 10 days following RT completion. Rates of complete prophylaxis (CP) for N&V, respectively (CP = no event and no rescue medication), were calculated for the acute phase (the period from the start of RT to the first day following RT completion inclusive) and the delayed phase (the second to tenth days following RT completion inclusive). RESULTS: Fifty-nine patients were enrolled, and 32 were evaluable. CP rates were as follows: moderate-risk SF group (n = 16), acute phase (CP for N = 56%, CP for V = 69%) and delayed phase (CP for N = 31%, CP for V = 44%); moderate-risk MF group (n = 7), acute phase (CP for N = 71%, CP for V = 57%) and delayed phase (CP for N = 43%, CP for V = 57%); low-risk SF group (n = 8), acute phase (CP for N = 50%, CP for V = 100%) and delayed phase (CP for N = 43%, CP for V = 57%); and low-risk MF group (n = 1), acute phase (CP for N = 100%, CP for V = 100%) and delayed phase (CP for N = 100%, CP for V = 100%). CONCLUSIONS: Despite prophylaxis, RINV was common among patients receiving palliative radiotherapy for bone metastases, especially during the delayed phase.

High dose rate brachytherapy in the management of anal cancer: A review.

PURPOSE: To conduct a systematic review evaluating the impact of high dose rate (HDR) brachytherapy (BT) on the clinical outcomes and toxicities of patients with anal cancer. METHODS AND MATERIALS: A search of Medline, Embase, and Cochrane Library databases was performed using search terms: "anal", "anal canal", "squamous", "adenocarcinoma", "cancer", "neoplasm", in combination with "brachytherapy", "high dose rate brachytherapy" or "HDR brachytherapy". Additional studies were identified after scanning references. Studies published in English with ≥10 patients were included. RESULTS: Ten studies (n = 448) were included in this review. 321 patients were treated with curative intent external beam radiotherapy (EBRT), chemotherapy (CT) and HDRBT; of those, 312 and 9 received interstitial and intraluminal BT, respectively. Mean follow up was 39.9 months (range (R): 24-61 months). Complete response was noted between 80%-93% and local control ranged between 81%-88%. Mean rate of local failure was 12.3% (SD 3.6%, R: 8%-18%). Distant failure rate was reported between 2%-3% and metastasis free survival ranged between 82%-88%. Mean disease free survival and overall survival were 77.3% (SD 6.6%, R: 66%-100%) and 82.5% (SD 13.7%, R: 70%-87.7%). Acute toxicity was mostly grade 1/2 dermatitis, proctitis or cystitis; G3 or higher toxicity was reported only in 4 patients in 2 studies (dermatitis n = 3 and sphincter necrosis n = 1). Most common long term toxicities were incontinence (2.5%-9%) and proctitis (2.5%-19%); G3/4 toxicity ranged between 2.2%-7.1%. Mean sphincter preservation rate and colostomy free survival was 88.0% and 80.4%, respectively. CONCLUSION: Pooled analysis in this review suggests excellent response, local control and survival with HDRBT in combination with EBRT and CT, with limited toxicity. Prospective well conducted trials are needed to further establish role of HDRBT management of anal cancer with future focus on development of international consensus on patient selection, dosimetric parameters, treatment sequencing as well as defining uniform outcome and toxicity assessment.

Round Cell Sarcoma with EWSR1-PATZ1 Fusion in the Face of a Five-Year-Old Boy: Report of a Case with Unusual Histologic Features.

Round cell sarcomas with EWSR1-PATZ1 fusion are rare polyphenotypic sarcomas that typically show both neural and myogenic differentiation on immunohistochemistry. The histology features lobular admixture of cellular fascicles of relatively monotonous spindle cells and small blue round cells separated by fibrotic stroma. The clinical behavior of EWSR1-PATZ1 sarcoma is uncertain currently with mixed outcomes reported even in cases with metastases. We herein report an additional case of EWSR1-PATZ1 fusion-related round cell sarcoma in the face of a 5-year-old boy with unusual histologic features of pale zones, rosette/gland-like structures and expression of epithelial markers. Fluorescent in-situ hybridization study (FISH) using EWSR1 breakapart probes was negative and molecular study with RNA sequencing was required to confirm the diagnosis. These findings highlight the diagnostic challenge and potential pitfall of FISH study in EWSR1-PATZ1 sarcoma. Further studies are required to increase the understanding of their behavior, morphologic spectrum and molecular features that will help devise new treatment strategies to these rare tumours.