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Discrimination of sensory signals is essential for an organism to form and retrieve memories of relevance in a given behavioral context. Sensory representations are modified dynamically by changes in behavioral state, facilitating context-dependent selection of behavior, through signals carried by noradrenergic input in mammals, or octopamine (OA) in insects. To understand the circuit mechanisms of this signaling, we characterized the function of two OA neurons, sVUM1 neurons, that originate in the subesophageal zone (SEZ) and target the input region of the memory center, the mushroom body (MB) calyx, in larval Drosophila. We found that sVUM1 neurons target multiple neurons, including olfactory projection neurons (PNs), the inhibitory neuron APL, and a pair of extrinsic output neurons, but relatively few mushroom body intrinsic neurons, Kenyon cells. PN terminals carried the OA receptor Oamb, a Drosophila α1-adrenergic receptor ortholog. Using an odor discrimination learning paradigm, we showed that optogenetic activation of OA neurons compromised discrimination of similar odors but not learning ability. Our results suggest that sVUM1 neurons modify odor representations via multiple extrinsic inputs at the sensory input area to the MB olfactory learning circuit.

Fatigue or tiredness is one of the most commonly reported symptoms in breast cancer patients treated with radiation therapy (RT). This study aimed to identify characteristics associated with fatigue in breast cancer patients receiving adjuvant RT.Patients with non-metastatic breast cancer receiving RT at the Odette Cancer Centre from 2011 to 2017 were included in our study if they completed at least one ESAS pre- and post-RT. Information regarding patient, disease and treatment characteristics was retrieved from chart review. To identify variables associated with fatigue scores pre-RT, post-RT and changes in fatigue scores, a univariate and multivariate general linear regression analysis was conducted; p 0.05 was considered statistically significant.Our study included 1223 female patients (mean age 59 years old) who completed ESAS on average 28 days before, and 142 days after RT. In multivariate analysis, higher baseline fatigue scores were found in women with higher disease stages (p = 0.001), and those who receive locoregional radiation (p 0.001). No variables were significantly associated with post-RT fatigue scores. While adjuvant chemotherapy and locoregional RT were associated with higher baseline scores in univariate analysis, in multivariate analysis, they were associated with significant reduction in fatigue post-RT (p = 0.01, p = 0.007 respectively).Fatigue is associated with higher disease stage and receipt of locoregional radiation. While the relationship between anxiety or depressive symptoms and fatigue is well-established, a major gap exists in our understanding of its etiology and treatment; further investigation to address this can better improve patient quality of life.

Despite having an excellent prognosis, patients with ductal carcinoma in situ (DCIS) report significant anxiety and depression following diagnosis. This study evaluated psychological morbidity using the Edmonton Symptom Assessment Scale (ESAS) in patients with DCIS compared with women with early-stage invasive breast cancer (EIBC) receiving radiotherapy (RT). We identified patients diagnosed with DCIS or EIBC (stage I or II breast cancer) from 2011 to 2017 who had at least one ESAS completed pre- and post-RT. Data on systemic treatment, radiation, patient demographics, and disease stage were extracted from existing databases. Psychological morbidity was evaluated through measurement of depression, anxiety, and overall wellbeing within the ESAS. The Wilcoxon rank-sum test or chi-square test was performed for continuous or categorical variables. This study included 137 women with DCIS and 963 women with EIBC. ESAS was completed on average 28 days before RT (baseline) and 142 days after RT. Baseline ESAS scores showed significantly higher rates of depression among women with EIBC compared with those with DCIS (p = 0.006). Patients with EIBC also reported higher levels of anxiety and lower overall wellbeing than patients with DCIS, but this difference was not statistically significant. Post-RT ESAS scores showed significantly higher anxiety in patients with EIBC compared with DCIS (p = 0.049). Post-RT measures of anxiety and overall wellbeing were higher in patients with EIBC but differences were not statistically significant. Women with DCIS experience relatively less psychological morbidity than women with EIBC, pre- and post-RT.

OBJECTIVE Seasonal effects on patients diagnosed with depression/anxiety-related psychological disorders have varying impacts on symptom severity. Seasonal changes in psychological distress may be due to decreased daylight exposure during the fall/winter seasons. Patients receiving radiation therapy (RT) for early-stage invasive breast cancer (EIBC) are at high risk for developing depressive symptoms. Of interest is whether seasonal factors influence the psychological symptoms of patients being treated for EIBC. METHODS Patients treated with RT for EIBC between January 2011 and June 2017 were identified. Patients who completed at least one Edmonton Symptom Assessment Scale (ESAS-r) pre-RT and post-RT were included in our analysis. Patients receiving RT during the autumn and winter (November-March) were compared with patients receiving RT during the spring and summer (April-August). Psychological distress was evaluated based on patient-reported depression, anxiety, and overall wellbeing on the ESAS-r. Data on systemic treatment and radiation were extracted from existing databases. RESULTS Eight-four patients treated with RT in spring/summer and 102 patients treated with RT in autumn/winter were included. Patients receiving RT during spring/summer had better wellness score prior to RT, compared with those receiving RT during winter/autumn (P = .03). However, patients receiving RT in the spring/summer had worse symptom trajectories across three domains of depression, anxiety, and wellbeing (P = .03, P = .008, and P < .0001, respectively). CONCLUSIONS Seasonality influenced the symptoms reported by patients with EIBC receiving RT. Future studies are needed to understand when during treatment patients are at highest risk for psychological distress and how seasonality may influence high-risk periods.

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). 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. A total of 426 patients provided data for the analysis. Overall acute pain increased significantly at week 1–2 (p

Background: Nausea and vomiting are commonly experienced by cancer patients, and can be assessed by the Functional Life Index-Emesis (FLIE) instrument which employs a three-day recall period. However, it is unknown whether patients’ responses to the FLIE better correlate with the average or the worst symptom severity of the recall period, or the severity of an individual day. Methods: Patients receiving emetogenic radiotherapy for painful bone metastases who were enrolled in one of three trials for anti-emetic medications (ondansetron, aprepitant/granisetron, or palonosetron) completed the FLIE at baseline, and days 3, 5, 7, or 10 during treatment and follow-up. The concordance correlation coefficient (rc) was calculated between FLIE overall nausea and vomiting and daily nausea, vomiting, and quality of life (QoL) using the average responses of the 3-day recall period and with each of the three days’ responses. Results: Responses from eighty-nine patients who experienced nausea or vomiting were analysed. The highest concordance for FLIE nausea was with the 3-day average [during treatment: rc =0.698, 95% confidence interval (CI): 0.495, 0.829; follow-up: rc =0.821, 95% CI: 0.711, 0.892]. FLIE vomiting had the highest concordance with worst day vomiting (during treatment, rc =0.310, 95% CI: 0.194, 0.417) or two day-prior vomiting (follow-up, rc =0.902, 95% CI: 0.832, 0.944). FLIE nausea and vomiting had inconsistent concordances with daily assessments of QoL. Conclusions: Responses to the FLIE questionnaire are most representative of average nausea severity. Larger cohorts to validate these findings are warranted to address the lack of power in this present study and to confirm the wording and justification of a three-day recall period for the FLIE.

Background: Approved almost 15 years ago for use in the chemotherapy setting, palonosetron, a 2nd generation 5-hydroxtryptamine 3 receptor antagonist (5-HT3 RA), has demonstrated efficacy in preventing chemotherapy-induced nausea and vomiting. However, its utility in the prophylaxis and treatment of radiation-induced nausea and vomiting (RINV) has yet to be evaluated. In this pilot study, we investigated the rates of control in RINV in patients with pre-existing emesis. Methods: Patients with pre-existing emesis undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2–10 after treatment). Prophylaxis and rescue (PR) was defined as a decrease in anti-emetic use, or episodes of nausea and/or vomiting from baseline. Complete prophylaxis (CP) was defined as no increase in anti-emetic use, or episodes of nausea and/or vomiting. Secondary endpoints included control of nausea and quality of life (QOL), as assessed with the Functional Living Index—Emesis and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire—Core 15 Palliative. Results: Fourteen patients were enrolled. Rates of control were higher in the acute phase (n=14) for nausea (PR =42.9%, CP =42.9%) and vomiting (PR =21.4%, CP =71.4%) compared to the delayed phase (n=13) for nausea (PR =42.9%, CP =7.7%) and vomiting (PR =15.4%, CP =53.8%). Conclusions: Palonosetron appears to be safe and patients with pre-existing emesis receiving palliative radiotherapy. More studies are needed to investigate its efficacy in this patient population.

Background: Palonosetron is an effective antiemetic in chemotherapy-induced nausea and vomiting (CINV), but has yet to be studied in the radiation setting. The purpose of the present study was to investigate the efficacy and safety of palonosetron in the prophylaxis of radiation-induced nausea and vomiting (RINV). Methods: Patients without existing nausea and vomiting undergoing palliative radiotherapy to sites with emetic risk were prescribed palonosetron 0.5 mg orally before the start of radiation treatment, and every other day until completion of treatment. Patients were followed up in acute (day 1 of treatment to day 1 after treatment) and delayed phases (days 2–10 after treatment). The primary endpoint was control of vomiting. Complete control was defined as no use of rescue medication and no episodes of nausea or vomiting. Secondary endpoints included control of nausea and quality of life (QOL). QOL was assessed with the Functional Living Index—Emesis and the European Organisation for Research and Treatment of Cancer QOL Questionnaire—Core 15 Palliative (C15-PAL). Results: In all evaluable patients (n=75), complete control of vomiting was 93.3% in the acute phase and 93.2% in the delayed phase. Complete control of nausea was 74.7% in the acute phase and 74.0% in the delayed phase. Conclusions: Results suggest improved control in RINV compared to historical reports with first generation serotonin receptor antagonists (RA). A randomized study will be needed to confirm this finding.

Background: Patients with advanced cancer often experience a multitude of symptoms. Due to the potential interrelation of symptoms, symptom clusters of 2 or more concurrent symptoms have been advocated for use in the palliative setting to provide better management of symptoms. Methods: The principal component analysis (PCA), exploratory factor analysis (EFA) and hierarchal cluster analysis (HCA) were conducted on responses to items 1–14 in the European Organisation for Research and Treatment of Cancer Quality of Life-C15-Palliative (EORTC QLQ-C15-PAL) at baseline and days 5 and 10 following RT. Results: There was complete data for 109, 90 and 87 patients at baseline, day 5 and day 10 respectively. The average age was 72 years. The most common site of primary was the prostate (36.7%), and almost all patients presented with bone metastases (95.4%). Analyses identified 2–4 clusters at each interval. From baseline to day 10 follow-up, across all analyses, items associated with physical functioning clustered consistently with shortness of breath. Pain and pain interference clustered with nausea at baseline; and with sleep at both follow-up intervals. Cronbach’s alpha values for the clusters ranged from 0.53 to 0.90. Conclusions: Fluctuation of symptom clusters was observed in a short time frame following palliative RT. Although clusters were dynamic, several items tended to cluster together. Further research is required to validate these clusters.

Despite the prevalence of radiation dermatitis in breast cancer patients, current practice guidelines for its treatment are limited. We aimed to discuss the quality of evidence for the barrier-forming Mepitel Film for prophylaxis of radiation dermatitis, and argue for further investigation into evidence-based management of skin toxicities. Two studies assessing Mepitel Film were critically evaluated. Both reported that Mepitel Film decreased radiation dermatitis; moreover, patient-reported outcomes significantly favoured Mepitel Film. However, there has not been global adoption of barrier-forming films such as Mepitel, in part due to the absence of multi-centred randomised trials and the heterogeneity of study designs.

Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic op-tions. Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population. This review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of cannabinoid-based therapies containing tetrahydrocannabinol (THC) and cannabidiol (CBD) for reducing cancer-associated pain. A review of literature published on Medline between 1975 and 2017 identified five clinical studies that evaluated the effect of THC or CBD on controlling cancer pain, which have been reviewed and summarised. Five studies that evaluated THC oil capsules, THC:CBD oromucosal spray (nabiximols), or THC oromucosal sprays found some evidence of cancer pain reduction associated with these therapies. A variety of doses ranging from 2.7-43.2 mg/day THC and 0-40 mg/day CBD were administered. Higher doses of THC were correlated with increased pain relief in some studies. One study found that significant pain relief was achieved in doses as low as 2.7-10.8 mg THC in combination with 2.5-10.0 mg CBD, but there was conflicting evidence on whether higher doses provide superior pain relief. Some reported side effects include drowsiness, hypotension, mental clouding, and nausea and vomiting. There is evidence suggesting that medical cannabis reduces chronic or neu-ropathic pain in advanced cancer patients. However, the results of many studies lacked statistical power, in some cases due to limited number of study subjects. Therefore, there is a need for the conduct of further double-blind, placebo-controlled clinical trials with large sample sizes in order to establish the optimal dosage and efficacy of different cannabis-based therapies.

Background: The purpose of this study was to assess symptom clusters in functional interference using the brief pain inventory (BPI) in patients with non-metastatic breast cancer (BC) during and after chemotherapy. Methods: A principal component analysis with varimax rotation was conducted on data from 228 patients to identify two clusters at baseline and two intervals following treatment. Results: Physical (general activity, normal work, walking ability) and psychosocial (mood, relationships, sleep, enjoyment of life) interference clusters were present at baseline. Clusters were observed at 1-month (cluster 1: general activity, normal work, enjoyment of life; cluster 2: relationships, sleep) and 3-month (cluster 1: general activity, normal work, relationships; cluster 2: sleep, enjoyment of life) post-treatment. Conclusions: Results from our study suggest dynamic symptom clusters in this patient population, and encourage continued symptom management following completion of treatment.

Heterotopic ossification (HTO) is the dystrophic formation of mature lamellar bone outside the confines of normal osseous tissues. It is frequently a complication which occurs following traumatic insult, both iatrogenic and non-iatrogenic, and neurological compromise. While mild degree of disease is often asymptomatic, significant pain and mobility limitations may result in reduced quality of life in advanced cases. Currently, the commonly accepted management for patients experiencing significant symptomatic HTOs is a combination therapy of surgical excision with prophylactic radiotherapy in the immediate perioperative period. In this article, we present a patient who achieved satisfactory pain relief and improvements in overall quality of life with the sole use of external beam radiation to illustrate the possibility of using radiotherapy alone for symptomatic management of HTO.

Palliative radiotherapy (RT) is effective in patients with painful bone metastases. Genetic factors may identify subgroup of patients who responded to RT. To identify DNA biomarkers associated with response to palliative RT.Patients who received a single 8 Gy dose of RT for painful bone metastases were categorised into responders (n=36), non-responders (NR) (n=71). Saliva samples were sequenced to identify single-nucleotide variants (SNVs) in genes with known disease-causing variants from inflammation, radiation response, and DNA damage pathways. In univariate analysis, Cochran-Armitage trend tests were used to identify SNVs that associated with pain response (P0.005), and the Penalized LASSO method with minimum Bayesian Information Criterion was used to identify multi-SNVs that jointly predict pain response to RT. The corresponding estimated effect of the multi-SNVs were used to drive the prognostic score for each patient. Based on it, patients were divided into 3 equal size risk groups.Forty-one significant variants were identified in univariate analysis. Multivariable analysis selected 14 variants to generate prognostic scores, adjusting for gender and primary cancer site. Eighty-nine percent of patients in the high prognostic group responded to palliative radiation therapy (P=0.0001). Estimated effect sizes of the variants ranged from 0.108-2.551. The most statistically significant variant was a deletion at position 111992032 in the ataxin gene ATXN2 (P=0.0001). Five variants were non-synonymous, including AOAH rs7986 (P=0.0017), ZAN rs539445 (P=0.00078) and rs542137 (P=0.00078), RAG1 rs3740955 (P=0.0014), and GBGT1 rs75765336 (P=0.0026).SNVs involved in mechanisms including DNA repair, inflammation, cellular adhesion, and cell signalling have significant associations with radiation response. SNVs with predictive power may stratify patient populations according to likelihood of responding to treatment, therefore enabling more efficient identification of beneficial strategies for pain management and improved resource utilisation.

Chemotherapy-induced neuropathic pain is a distressing and commonly occurring side effect of many commonly used chemotherapeutic agents, which in some cases may prevent cancer patients from being able to complete their treatment. Cannabinoid based therapies have the potential to manage or even prevent pain associated with this syndrome. Pre-clinical animal studies that investigate the modulation of the endocannabinoid system (endogenous cannabinoid pathway) are being conducted to better understand the mechanisms behind this phenomenon. Five recent pre-clinical studies identified from Medline published between 2013 and 2016 were selected for review. All studies evaluated the effect of small-molecule agonists or antagonists on components of the endocannabinoid system in rats or mice, using cisplatin or paclitax-el-induced allodynia as a model of chemotherapy-induced neuropathic pain. Activation of the cannabinoid receptor-2 (CB-2) receptor by AM1710 blocked paclitaxel-induced mechanical and cold allodynia in one study. Four studies investigating the activation of both cannabinoid receptor-1 (CB-1) and CB-2 receptors by dual-agonists (WIN55,21 and CP55,940), or by the introduction of inhibitors of endocannabinoid metabolisers (URB597, URB937, JZL184, and SA-57) showed reduction of chemotherapy-induced al-lodynia. In addition, their results suggest that anti-allodynic effects may also be mediated by additional receptors, including TRPV1 and 5-hydroxytryptamine (5-HT1A). Pre-clinical studies demon-strate that the activation of endocannabinoid CB-1 or CB-2 receptors produces physiological effects in animal models, namely the reduction of chemotherapy-induced allodynia. These studies also provide in-sight into the biological mechanism behind the therapeutic utility of cannabis compounds in managing chemotherapy-induced neuropathic pain, and provide a basis for the conduct of future clinical studies in patients of this population.

To explore the age difference in response and patient-reported outcomes in patients with cancer having bone metastases undergoing palliative radiotherapy.Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life (QOL) Bone Metastases module (QLQ-BM22), EORTC QOL Core-15-Palliative (QLQ-C15-PAL), and Dexamethasone Symptom Questionnaire (DSQ) before a single 8-Gy radiation treatment, on days 10 and 42 after treatment. Patient demographics, performance status, analgesic consumption, BM22, C15, and DSQ were compared with multivariant analysis between patients under 75 years and 75 years and older. Multiple linear regression models were used to assess the differences between age-groups, adjusting for baseline demographics and primary disease sites.There were 298 patients (170 male) with 209 (70%) less than 75 years of age. Most common primary cancer sites include lung, prostate, and breast. At baseline, younger patients had better performance status, consumed more analgesic, and reported worse scores in nausea, insomnia, and functional interference, while older patients more commonly had prostate cancer. There were no significant differences in the incidence of radiation-induced pain flare; response to radiation; changes from baseline for BM22, C15-PAL; and DSQ, nor overall survival at day 42 between the 2 groups. Responders to radiation in the elderly group reported better improvement in physical and emotional domains when compared with nonresponders.In patients with cancer having bone metastases undergoing palliative radiotherapy, there was no significant difference in general with age in response to radiation and patient-reported outcomes. Palliative radiotherapy should be offered to elderly patients when needed.

Bone metastases cause pain, suffering and impaired quality of life (QoL). Palliative radiotherapy (RT) and/or chemotherapy are effective methods in controlling pain, reducing analgesics use and improving QoL. This study goal was to investigate the changes in QoL scores among patients who responded to palliative treatment.A prospective study evaluating the role of radiation therapy in a public academic hospital in São Paulo-Brazil recorded patients' opioid use, pain score, Portuguese version of QLQ-BM22 and QLQ-C30 before and 2 months after radiotherapy. Analgesic use and pain score were used to calculate international pain response category. Overall response was defined as the sum of complete response (CR) and partial response (PR). CR was defined as pain score of 0 with no increase in analgesic intake whereas PR was defined as pain reduction ≥2 without analgesic increase or analgesic reduction in ≥25% without increase in pain at the treated site.From September 2014 to October 2015, 25 patients with bone metastases responded to RT or chemotherapy (1 CR, 24 PR). There were 8 male and 17 female patients. The median age of the 25 patients was 59 (range, 22 to 80) years old. Patient's primary cancer site was breast [11], prostate [5], lung [2], others [7]. For QLQ-BM 22, the mean scores of 4 categories at baseline were: pain site (PS) 39, pain characteristics (PC) 61, function interference (FI) 49 and psycho-social aspects (PA) 57. At 2 month follow up, the scores were PS 27, PC 37, FI 70 and PA 59. Statistical significant improvement (P0.05) was seen in PS, PC, FI but not PA. In the QLQ-C30, the scores were not statistically different for all categories, except for pain that demonstrated a 33 point decrease in the median pain score domain (66 to 33).Responders to RT at 2 months presented improvement in BM22 and C30 pain domains, and also improvement in functional interference domain of the BM22 questionnaire.

The purpose was to retrospectively examine the anti-emetic regimens prescribed for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) for head and neck cancer patients receiving moderate- or high-emetogenic chemotherapy (MEC/HEC) along with concurrent radiation treatment at an outpatient ambulatory care center to determine the efficacy of anti-emetics prescribed.Consecutive patients with head and neck cancers who initiated cisplatin chemotherapy with concurrent radiation treatment between January 2013 and June 2015 were investigated. Patients' anti-emetic use and occurrence of CINV was extracted from available clinical documentation. Patients were divided into two cohorts: CISPL-HIGH (n=161), and CISPL-WEEKLY (n=38).A total of 199 head and neck cancer patients (158 male, 41 female) were included in the analysis (mean age =59 years). In the CISPL-HIGH cohort, 33 males (26%) and 16 females (49%) experienced CINV. In the CISPL-WEEKLY cohort, four males (13%) and two females (25%) experienced CINV. Nausea occurred in 71 patients (62 HEC and 9 MEC). The odds of achieving complete response (no nausea or vomiting) were 3.5 (P0.0016) times more likely for patients receiving MEC. Overall, the complete response rate for the prophylaxis in MEC and HEC was 61% and 31%, respectively. Anti-emetic changes occurred in 34% and 11% of patients receiving HEC and MEC, respectively.In the current study CINV control for patients receiving HEC was sub-optimal. Changes to our prophylactic antiemetic regimens may help improve patient outcomes.

Background and purpose Impending or pathological fractures due to bone metastases may require surgical fixation. Postoperative radiation is often recommended to reduce local progression and prevent prosthesis displacement, hence reducing the need for second surgery. The objectives of this study were to investigate the need for second surgery, and to report on rates of re-irradiation, tumor progression and prosthesis displacement following postoperative radiation. Materials and methods Data were collected from 65 patients who received postoperative radiation to 74 sites in the extremities in a palliative radiation clinic between January 2009 and January 2017. Descriptive statistical analyses were performed. Results Only 2 patients required a second surgery (2.7%) at 9 and 10months after postoperative radiation. Increase in pain requiring re-irradiation was reported in 7 patients (9.5%), at a median time of 9.3months after the delivery of radiation. Of the 47 patients who had radiological imaging available post-radiation, local progression of bone metastases was seen in 8 patients (17.0%) and displacement of the prosthesis in 1 patient (2.1%). Conclusion Rates of prosthesis displacement and progression of bone metastases at site of surgery were low after postoperative radiation. There were few incidences of second surgery and re-irradiation observed in the cohort. These findings provide support for the benefit of postoperative radiation.

To identify symptom clusters in advanced cancer patients attending a palliative radiotherapy clinic using the Edmonton Symptom Assessment System (ESAS). Principal component analysis (PCA), exploratory factor analysis (EFA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the nine ESAS items using scores from each patient’s first visit. ESAS scores from 182 patients were analyzed. The PCA identified three symptom clusters (cluster 1: depression-anxiety-well-being, cluster 2: pain-tiredness-drowsiness, cluster 3: nausea-dyspnea-loss of appetite). The EFA identified two clusters (cluster 1: tiredness-drowsiness-loss of appetite-well-being-pain-nausea-dyspnea, cluster 2: depression-anxiety). The HCA identified three clusters similar to the PCA with an exception of the loss of appetite item being classified under cluster 1 rather than 3. Two to three symptom clusters were identified using three analytical methods, with similar patterns reported in the literature. Particular groups of items co-occurred consistently across all three analyses: depression and anxiety; nausea and dyspnea; as well as pain, tiredness, and drowsiness. Three similar symptom clusters were identified in our patient population using the PCA and HCA; whereas, the EFA produced two clusters: one physical and one psychological cluster. Given the implications of symptom clusters in the management of quality of life, clinicians should be aware of these clusters to aid in the palliative treatment of patients.

Focused ultrasound (FUS) for palliation of bone metastases has typically been performed under magnetic resonance guidance. To address limitations of this approach, this pilot study evaluated a stand-alone, portable FUS device guided by diagnostic ultrasound alone (ultrasound [US]-guided FUS). Nine patients were treated; safety and efficacy were assessed for 10 d after the procedure, and medical charts were evaluated to assess durability of pain response. The procedure was safe and tolerable, with four patients reporting minor skin-related irritations. Average pain score decreased from 6.9 at baseline to 3.2 at day 10; analgesic use on average also decreased from baseline to day 10. Six patients had durable pain relief as assessed after the follow-up period. Our study provides evidence that US-guided FUS is a safe, tolerable and versatile procedure. It appears to be effective in achieving durable pain response in patients with painful bone metastases. Further research is required to refine the technology and optimize its efficacy.

Purpose Symptoms experienced by breast cancer patients often cluster together in groups known as “symptom clusters”. The aim was to determine the symptom clusters in women with non-metastatic breast cancer treated by radiation therapy (RT). Methods Edmonton Symptom Assessment Scale (ESAS) scores were taken from breast cancer patients receiving RT before, at completion of RT, and after RT. Exploratory factor analysis (EFA), principal component analysis (PCA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the nine ESAS items at all three time points. Results This study included 1224 patients. The PCA and EFA identified the same two symptom clusters before the start of RT: 1) pain, tiredness, nausea, drowsiness, appetite, and dyspnea; 2) depression, anxiety, and wellbeing. The HCA further split the symptoms into three clusters. Wellbeing, depression, and anxiety consistently clustered together. Among the ESAS scores collected at the end of and after RT, each statistical method identified different symptom clusters. For the symptom clusters experienced at the end of RT, the following symptoms were always in the same cluster: wellbeing, depression, and anxiety; nausea and appetite; drowsiness and dyspnea. Following RT, depression and anxiety consistently clustered together, with nausea and appetite in a second cluster. Conclusion Among the symptom clusters derived before, at the end of RT, and after RT, the following symptoms consistently presented together: depression and anxiety, nausea and appetite, pain and tiredness, and drowsiness, dyspnea, and tiredness. Understanding symptom clusters in this population can improve management of symptoms.

Background Breast cancer patients often experience multiple symptoms that negatively affect quality of life (QOL). Patient-reported scores on symptom screening tools are used by health care professionals to manage QOL. We aimed to examine which symptoms from the Edmonton Symptom Assessment Scale (ESAS) were most predictive of overall well-being (QOL) in breast cancer patients over the course of radiotherapy (RT). Patients and Methods ESAS results completed before, at the end of, and after RT were obtained from all nonmetastatic breast cancer patients. Univariate and multivariable (backward stepwise selection) linear regression analyses were applied to select the most significant ESAS symptoms or treatment variables related to overall QOL at all 3 time points. Results A total of 1224 patients were included in the study. Before RT, multivariable analysis identified 5 symptoms that were significantly associated with overall QOL: pain, tiredness, anxiety, depression, and loss of appetite. At the end of RT, pain, tiredness, and anxiety were the most significant predictors of QOL. After RT, 6 symptoms were found to have the strongest correlation with QOL: pain, tiredness, anxiety, depression, loss of appetite, and drowsiness. At each time point, patients with higher scores for the identified significant symptoms were likely to have a worse overall QOL. Conclusion Of the ESAS symptoms identified as significant predictors of QOL, pain, tiredness, and anxiety correlated with overall well-being at all time points. Special attention should be paid to manage symptoms that are most predictive of overall QOL in order to ensure optimal symptom management in breast cancer patients receiving RT.

The use of hypofractionated radiotherapy (HFRT) in patients with breast cancer and ductal carcinoma in situ (DCIS) in Ontario, Canada, from 2009 to 2015 was reported. A retrospective cohort study was conducted using data from the Institute for Clinical Evaluative Sciences (ICES). Patients with a breast cancer or DCIS diagnosis between 2009 and 2015 who received adjuvant breast or chest wall radiation were included. Trends in HFRT use (≤16 fractions) and factors associated with HFRT use in a multivariable logistic regression model with physician-level random effect were reported. The approximate number of hours that could be saved if all patients were to receive HFRT was calculated. A total of 42 072 patients were included. All included characteristics were significantly associated with HFRT use. Hypofractionated radiotherapy use in patients with breast cancer and DCIS increased to around 75% in 2015. In stage I/II patients with mastectomy and chest wall radiation, HFRT use increased to 40% in 2015. Hypofractionated radiotherapy use in patients with regional nodal radiation or reconstruction has increased but remains under 20%. For breast cancer patients with breast-conserving surgery (BCS) and breast radiation, 56 265 visits corresponding to 7200 hours of treatment or 3500 additional HFRT courses could have been saved. In conclusion, HFRT use in Ontario has increased in all patient populations but is nonuniform among physicians and institutions. Use of HFRT in chest wall and regional nodal radiation remains relatively lower than in breast cancer and DCIS patients with BCS.

Taxane acute pain syndrome (TAPS) is a clinically significant side-effect of taxane chemotherapy, often described as arthralgia and myalgia that occurs 2–3 days after infusion. The aim of this study was to assess pain descriptors used by patients during their experience of TAPS. A clinical prospective cohort study was conducted on breast cancer patients who had not received prior chemotherapy and were asked to complete diaries on three consecutive docetaxel treatment cycles on days 1–7, 14, and 21 (acute phase). Questionnaires to assess pain severity, descriptors of pain, and the interference in activities due to pain were adapted from the Brief Pain Inventory and the McGill Pain Questionnaire. Telephone questionnaire follow-up was done at 1, 3, 6, 9, and 12 months following docetaxel (delayed phase). The most commonly used descriptor for acute and chronic pain was “aching” (90–96%). However, in the delayed phase of the study, “burning” (32–50%), “radiating” (39–48%), and “sharp” (40–69%) were used more often. In both acute and chronic pain phases, most patients experienced moderate/severe pain regardless of the location. Pain in cycle 1 was predictive of pain in subsequent taxane cycles (p

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxane treatment during chemotherapy. Identifying predictive biomarkers of CIPN would allow physicians to alter treatment given to patients according to a personal risk of developing this condition. The current literature on CIPN biomarkers is reviewed, identifying biomarkers which have been found to be significantly related to CIPN. Three genetic biomarkers are identified (ARHGEF10 rs9657362, CYP2C8 rs11572080/rs10509681 and FGD4 rs10771973) which have been found to act as predictive CIPN biomarkers in multiple studies. Possible mechanisms underlying the relationship between these single nucleotide polymorphisms and CIPN development are explored. The biomarkers identified in this study should be investigated further to generate predictive biomarkers that may be used in a clinical setting.

The insect mushroom bodies (MBs) are essential for associative olfactory learning, and their sensory input region, the MB calyx, is organized in discrete glomeruli, most of which receive stereotypic input from olfactory projection neurons (PNs). Odors are represented by activity of MB neurons, the Kenyon Cells (KCs) using a sparse code that allows odor discrimination during learning. Octopamine (OA) is a neurotransmitter that signals reward in associative learning and arousal, in insects including Drosophila. The calyx receives OA innervation from two neurons, sVUMmd1 and sVUMmx1, originating from their respective neuromeres in the suboesophageal zone (SEZ). To understand how these OA inputs might influence odor discrimination in the MBs, we analyzed their pattern of innervation of the MB calyx, their connectivity with the other neurons that innervate the calyx, and their influence on sensory discrimination during learning. Clonal labeling of multiple single neurons showed that the two sVUM1 neurons innervated all regions of the calyx. GRASP (GFP Reconstitution Among Synaptic Partners) revealed contacts of sVUM1 neurons in the calyx with olfactory PNs, the inhibitory neuron APL, extensively with an extrinsic neuron with dendrites throughout the calyx, but not with KCs. A GFP protein trap of the OA receptor Oamb, a Drosophila alpha-1-adrenergic receptor ortholog, localized to PN terminals in the calyx. In a behavioral odor discrimination assay, activating a set of 5 OA neurons, including the sVUM1 neurons, compromised the ability to discriminate similar odors. Our results support a model, in which OA release from sVUM1 neurons can modify release from PN terminals, thus increasing the sensitivity but decreasing discrimination in the olfactory learning pathway.

Radiotherapy-induced nausea and vomiting is a common side effect of radiotherapy. It is well-established that nausea and vomiting have a negative impact on quality of life, but the relative influence of each of symptom is infrequently reported. This study aimed to compare the effects of nausea and vomiting on quality of life in cancer patients receiving palliative radiotherapy. The Functional Living Index-Emesis (FLIE) is a quality of life questionnaire developed in the chemotherapy-induced nausea and vomiting setting. The FLIE consists of 18 questions, half of which address nausea and half of which address vomiting. Three prospective studies on the efficacy of various anti-emetic medications conducted at our center used the FLIE to assess radiotherapy-induced nausea and vomiting at various time points during and after palliative radiotherapy. FLIE data from these three studies were combined for the present analysis. Univariate and multivariate analyses were conducted to assess the relationships between nausea and vomiting, time of FLIE completion, and patient-reported quality of life. Nausea and vomiting scores both decreased patients’ quality of life. Multivariate modeling showed that both symptoms significantly influenced patients’ ability to enjoy meals. Nausea was also associated with increased hardship for the patient, while vomiting imposed more difficulty on the patients’ loved ones. Nausea and vomiting both significantly influence quality of life. Nausea seems to impact the patient more directly, whereas vomiting affects those closest to the patient.

Background Phyllodes tumours are rare and histologically diverse, posing challenges in prognosis and treatment. Due to their rarity, they have seldom been studied. Purpose The purpose was to investigate clinical practices in the management of phyllodes tumours, as well as patient outcomes to contribute to the limited body of knowledge surrounding these tumours. Methods A retrospective review was conducted on all patients with phyllodes tumours at a single institution. Descriptive analyses were conducted on demographic, disease and treatment (breast-conserving surgery, mastectomy, surgical re-excision, adjuvant/palliative radiation, palliative chemotherapy) information. Overall and disease-free survivals were analyzed, and the cumulative incidence of recurrence and metastases was compared. Results 79 patients with phyllodes tumours of the breast were included in the study. Tumours were classified as malignant, borderline, or benign in 67.1%, 21.5%, and 11.4% of patients, respectively. There were no statistically significant differences in overall or disease-free survival between patients with benign, borderline or malignant disease. Only patients with malignant disease developed recurrence or metastases. Those with malignant disease who received mastectomies had a lower 10-year cumulative incidence of recurrence; however this was not statistically significant (p = 0.69). All patients had negative surgical margins due to a re-excision or mastectomy following margin-positive breast conserving surgery. Of all risk factors assessed, necrosis was significantly associated with increased incidence of recurrence (local or distant) in patients with malignant disease (p = 0.03). Conclusion The presence of tumour necrosis is a significant negative prognostic factor. Breast-conserving surgery may be adequate in providing local control, given negative surgical margins.

Palliative care aims to improve quality of life (QoL) for patients and families and does so by addressing issues not limited to pathology, but other symptoms that may be debilitating to patient experience and QoL. Despite sexual health being an important aspect of life for many patients, it is often omitted in clinical practice. This review summarizes published primary studies to explore the prevalence and importance of incorporating sexual health in the symptom screening and assessments of palliative patients, to identify current interventions that are implemented to address sexual health issues, and identify the barriers that health care professionals (HCPs) and patients may encounter which may prevent sexual health discussions. A literature review was conducted on Medline and Embase databases using keywords including "cancer", "sexual health", "intimacy", and "palliative care". Eleven papers focusing on the sexual health and intimacy of terminally ill patients in hospice, palliative or terminal care settings were identified for inclusion. Discussions about sexual health, functioning, and intimacy were not common in patient care, despite being a service that both patients and their partners desired. Referrals to sexologists, or discussions with patients and partners about intimacy and sexuality over the course of the disease trajectory were shown to improve QoL as well as alleviate some of the stress of receiving palliative care services. HCPs cited a lack of training, their own life experiences, or discomfort with the topic as barriers to initiating conversations with patients. In conclusion, sexuality and intimacy remain important parts of many people's lives regardless of their health, and should be incorporated into the care of all patients including those in palliative care. There is a need for further research to evaluate different methods or procedures for educating and counselling patients and their partners on sexual health issues. HCPs should have specific training and education in sexual health care to enable them to initiate and direct these discussions.

Patients with bone metastases undergoing palliative radiation therapy (RT) may experience changes in both the functional and symptomatic aspects of quality of life (QOL). The European Organization of Cancer Research and Treatment (EORTC) QOL Questionnaire Core-15 Palliative (QLQ-C15-PAL) is a validated questionnaire employed to assess QOL specifically in palliative patients. Our study aimed to identify single-nucleotide variant (SNV) genetic biomarkers associated with changes in QOL and pain.Fifty-two patients who received a single 8-Gy RT for painful bone metastases completed the EORTC QOL-C15-PAL questionnaire prior to randomization and at 42-day post RT. Saliva samples obtained at day of RT were sequenced, and SNVs from genes involved in inflammation, radiation response, immune response, DNA damage, or QOL were assessed for association with changes in global QOL or the pain scale items using the Cochran-Armitage trend test. The penalized LASSO method with minimum Bayesian information criterion was used to select a multi-SNV model out of significant SNVs (P0.005) and to produce prognostic scores for patients that categorized them into risk groups of low, middle, and high.The multivariable model predicting global QOL included 14 SNVs, of which HS1BP3 rs35579164 G:C and ABCA1 rs2230805 CT had the largest positive and negative effect sizes, respectively (HS1BP3: 8.21, ABCA1: -3.44). The model for the response of QOL pain item included 8 SNVs, of which PLAUR rs4760 AG and ELAC2rs11545302 had the largest positive and negative effect sizes, respectively (PLAUR: 5.23; ELAC: -3.84). The patients' risk groups were highly predictive of QOL response (P0.0001) and pain item response (P0.0001). In logistic regression analysis accounting for baseline factors of gender and primary cancer site, the global QOL risk group predicts pain response after RT [OR: 2.1, 95% confidence interval (CI): 1.2-3.9, P=0.015], but the QOL pain item risk group did not (OR: 0.93; 95% CI: 0.5-1.6, P=0.79). The multi-SNVs model included SNVs from genes involved in metabolism, membrane transport, cell cycle control, ciliary structure, and gene expression regulation.SNVs were significantly associated with changes in global QOL of global domain and pain item in patients with bone metastases. Identification of genetic biomarkers predictive of QOL items may allow patients and health care providers anticipate and better address the needs of the palliative cancer patient population.

Background: Pain is reported in approximately 50–70% of cancer patients. Studies on gender differences in perceived pain generally report lower pain thresholds and increased pain prevalence in women, which may be attributed to gender-specific behaviors, stereotypes, and unknown etiological factors. There are sparse and inconclusive results on gender differences in self-perceived pain in the cancer setting. The aim of this article was to examine the effect of gender on baseline perceived pain intensity in cancer patients through a meta-analysis. Methods: A literature search was conducted using Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials [1947–2016] to identify observational studies and controlled trials that reported on gender-specific pain intensity in cancer patients. Using random-effects modeling, weighted mean differences and 95% confidence intervals (CI) were used to estimate the effect of gender on pain severity in cancer patients. A P value of less than 0.05 was considered statistically significant. Results: Of the 1,911 search results reviewed, 13 studies were included. The weighted mean difference (95% CI) in pain intensity was as follows: −0.26 (95% CI: −0.57 to 0.04, P=0.09) for the 0–10 Numerical Rating Scale (NRS) group (n=3,752, 9 studies). When restricted to only patients with advanced cancer, the weighted mean difference was −0.08 (95% CI: −0.36 to 0.20, P=0.58) (n=2,762, 4 studies). The weighted mean difference in the Brief Pain Inventory scores between males and females was 0.03 (95% CI: −1.23 to 1.29, P=0.96) (n=521, 4 studies). Conclusions: Baseline perceived pain intensity in cancer patients did not significantly differ based on gender.

Background: Pelvic radiation may cause radiation enteritis, which commonly manifests as diarrhea. Radiation to the abdomen or pelvis may also cause radiation-induced nausea and vomiting (RINV) which is often treated with anti-emetics such as serotonin (5-HT3) receptor antagonists (RA). However, a common side effect of these anti-emetic medications is constipation. Both diarrhea and constipation can have a significant impact on patient quality of life (QOL). The objective of this study was to assess the prevalence of diarrhea and constipation in patients receiving pelvic radiation and anti-emetics. Methods: Patients undergoing pelvic radiation between January 2011 and March 2017 at Sunnybrook Odette Cancer Centre were enrolled in three prospective clinical trials studying the efficacy of various anti-emetics for RINV prophylaxis. Patients completed QOL questionnaires which included a single question about severity of constipation at baseline, day 5 and 10 during radiation if applicable, and day 5 and 10 after completion of radiation; severity was measured on a 4-point Likert scale ranging from 1= “not at all” to 4= “very much”. Patients also recorded severity of diarrhea throughout baseline, treatment, and 10 days follow-up via daily diaries; responses were qualitative ranging from “no diarrhea” to “severe diarrhea” on a 4-point scale. Results: Fifty-nine patients received pelvic radiation across the three trials. The average constipation score at baseline was 1.69 [standard deviation (SD) 0.93], and increased up to 2.33 (SD 1.03) at day 10 during treatment. Following treatment, the average score decreased to 1.61 (SD 0.80) at day 10 follow-up with the majority of patients reporting no constipation at this time (57.7%). The average diarrhea score at baseline was 1.03 (SD 0.18) and remained stable throughout treatment and follow-up. A vast majority of patients reported no diarrhea after day 10 follow-up (96.4%). Conclusions: Constipation was more prevalent than diarrhea during radiation treatment and up to day 10 after radiation to the pelvis. Approximately 42% of patients will have constipation on day 10 post radiation. Further research is needed to assess the causes of constipation including analgesics, and the effect on QOL during and shortly after palliative radiation to the pelvis.

Background: Bone metastases clinic (BMC) is a multidisciplinary clinic where patients with bony metastases are assessed in conjunction by orthopedic surgery, radiation oncology, interventional radiology, and palliative medicine teams. The objective of the study was to determine the number of older adult (OA) referrals made to BMC and to examine their case dispositions. Methods: Patients who were referred to the BMC from 2007 to 2015 were included in the study. Demographic information including gender, age, Karnofsky Performance Status (KPS), primary cancer site and reason for referral, as well as case dispositions were recorded for each patient. The proportion of OA attendance was calculated for each year from the total number of patient visits. OA attendance was defined as individuals ≥65 years of age who attended the BMC, and non-OA patients were those Results: A total of 551 patients were included with a median age of 64 years. The median KPS was 70 for OA and 80 for non-OA patients. OA attendance ranged per year from 42.5% to 58.7%. 14.1% of non-OA and 10.9% of OA patients were offered surgery. 62 patients in both cohorts (22.6% of OA and 22.4% of non-OA patients) were offered palliative radiation. Conclusions: From 2007 to 2015, OA patients comprised a significant proportion of referrals to the BMC. Younger patients were offered surgery slightly more often when compared to OA patients. Age did not appear to be a precluding factor for BMC referral or a deterrent in treatments offered.

Background and purpose Single fraction radiation treatment (SFRT) is recommended for its equivalence to multiple-fraction (MF) RT in the palliation of uncomplicated bone metastases (BM). However, adoption of SFRT has been slow. Materials and methods Literature searches for studies published following 2014 were conducted using online repositories of gray literature, Ovid MEDLINE, Embase and Embase Classic, and the Cochrane Central Register of Controlled Trials databases. Results A total of 32 articles detailing patterns of practice and clinical practice guidelines were included for final synthesis. The majority of organizations have released high level recommendations for SFRT use in treatment of uncomplicated BM, based on evidence of non-inferiority to MFRT. There are key differences between guidelines, such as varying strengths of recommendation for SFRT use over MFRT; contraindication in vertebral sites for SFRT; and risk estimation of pathologic fractures after SFRT. Differences in guidelines may be influenced by committee composition and organization mandate. Differences in patterns of practice may be influenced by individual center policies, payment modalities and consideration of patient factors such as age, prognosis, and performance status. Conclusion Although there is some variation between groups, the majority of guidelines recommend use of SFRT and others consider it to be a reasonable alternative to MFRT.

Background: Hypomethylating agents (HMAs) can confer transfusion independence and prolong overall survival (OS) in patients with myelodysplastic syndromes (MDS), but response rates are < 50% and depend on sustained administration. In Ontario, 33% of higher risk MDS patients receive < 4 cycles AZA and have very short survival. Identifying the patients unsuitable for HMAs and the factors predictive of overall survival (OS)/leukemia free survival (LFS) would be of value. MDS-CAN, the national MDS registry prospectively evaluates patient-related factors in addition to disease factors in MDS, MDS/MPN, and oligoblastic AML patients. Objective: Determine the factors predictive of OS/LFS and the completion of ≥ 4 cycles of HMA, with particular focus on frailty and comorbidity. Methods: All patients who had received HMAs (azacytidine (AZA), decitabine, guadecitabine, ASTX727) were eligible. Frailty was assessed using the Rockwood clinical frailty scale (CFS) and the frailty index (FI) comprised of 42 deficits we previously developed. The MDS-FI was calculated using baseline measurements of comorbidities, laboratory values, Lawton Brody instrumental activities of daily living (LB-IADL), quality of life (EQ-5D), and 3 physical fitness tests. Patients who had ≤ 13 missing variables on the MDS-FI were included. Kaplan-Meier (KM) OS curves were calculated from treatment start date to death or last follow up. Univariable and multivariable analysis was done to identify significant predictors of OS, LFS and the receipt of ≥ 4 cycles of HMA. Results: There were 422 patients treated with an HMA (94% AZA). FI scores could be calculated in 188 patients and CFS in 169 patients. Among the 188 patients, the median age at HMA start was 73 years old (IQR 67, 79), time from diagnosis was 10 months (IQR 2, 28), 66% of patients were high/intermediate-2 risk IPSS, and 72% were high/very high risk IPSS-R. 40% were transfusion dependent, 30% had poor/very poor cytogenetics, and 10% had oligoblastic AML. Median number of HMA cycles was 7 and 76% completed ≥ 4 cycles. The median follow up was 12 months (IQR 7, 25). 19% of patients developed AML. Actuarial median OS was 17 months (95% CI: 13-20) with 50% of deaths due to AML or progressive disease. The MDS-FI score was grouped into categories of 1, 2, and 3 (scores ≤0.2, 0.2-3, and >3, respectively), with a median score of 0.3 (IQR 0.2, 0.3). The median scores for the clinical frailty scale (CFS), Charlson comorbidity index (CCI), and MDS-specific comorbidity index (CI) were 3 (IQR 2, 4), 1 (IQR 0, 2), and 0 (IQR 0, 2) respectively. 21% of patients had cardiac comorbidity(s), 53% had ≥ 1 disability (LB-IADL), and 76% had ≥ 1 impaired symptoms or function on the EQ5D, the most common being usual activities (45%) and pain/discomfort (44%). On physical testing, 56%, 30% and 88% had partial or full deficits in grip strength, 4 meter walk and the 10x chair stand tests compared with age/sex matched reference standards. Those who completed ≥ 4 cycles of AZA compared with those that did not were more likely to be younger (73 vs 78 years old, p=0.002), have lower risk disease (IPSS-R very low/low/intermediate: 29 versus 13%, p=0.044), have lower comorbidity (MDS-CI score: 0 vs 1, p=0.006), lower frailty scores (CFS: 2 versus 3, p=0.008) and performed better on grip strength (31 vs 26 kg, p=0.021) and the 10x chair stand test (28 vs 30s, p=0.045). Predictive factors from univariate analysis are presented on Table 1. There was a trend towards receiving fewer HMA cycles if patients fell within higher FI categories (8 vs 7 vs 5 cycles, p=NS). OS declined with increasing FI categories (p=0.002, Fig 1a). In subgroup analysis by IPSS or IPSS-R score, the FI further stratified the OS of patients with IPSS high/intermediate-2 (p=0.001, Fig 1b) and IPSS-R very high/high risk groups (p=0.002, Fig 1c). The best multivariate model for OS included IPSS (p=0.001), LDH (p=0.001), and MDS-CI (p Conclusions: Frailty and comorbidity provide important prognostic information for clinical outcomes in MDS patients receiving hypomethylating agents. The evaluation of patient characteristics in addition to disease parameters should be an integral part of clinical decision-making. Disclosures Wells: Alexion: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Rockwood:Alzheimer Society of Canada: Research Funding; Lundbeck: Membership on an entity's Board of Directors or advisory committees; Canadian consortium on neurodegeneration in aging and nutricia: Membership on an entity's Board of Directors or advisory committees; Foundation Family Fund: Research Funding; Pfizer: Research Funding; Capital Health research support: Research Funding; Sanofi: Research Funding; CIHR: Research Funding; Nova Scotia Health research foundation: Research Funding. Geddes:Celgene: Honoraria, Research Funding; Alexion: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Sabloff:Actinium Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees; Sanofi Canada: Research Funding; Astellas Pharma Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees; ASTX: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees. Keating:Sanofi: Membership on an entity's Board of Directors or advisory committees; Hoffman La Roche: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy; Novartis: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees. Leber:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Leitch:Celgene Corporation: Honoraria, Research Funding; Otsuka: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Alexion: Research Funding; AbbVie: Research Funding. Yee:Takeda: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astex: Research Funding; Hoffman La Roche: Research Funding; MedImmune: Research Funding. St-Hilaire:Teva: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Finn:Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Ipsen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Lundbeck: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Storring:Novartis: Honoraria, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Nevill:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Paladin Labs: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shamy:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Abbie: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees. Banerji:Roche: Honoraria, Licensing fee, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; LLSC: Research Funding; Research Manitoba: Research Funding; CCMF: Research Funding; CancerCare Manitoba/University of Manitoba: Employment; CAPhO: Honoraria; BIOGEN: Other: Licensing fee; Dana-Farber Cancer Institute: Other: Licencing fee; Abbvie: Consultancy, Honoraria; CIHR: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Consultancy, Honoraria. Delage:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Buckstein:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding.

e12019 Background: Patients who receive radiotherapy (RT) for breast cancer often report pain and fatigue which contribute negatively to quality of life (QoL). We aim to identify demographic, treatment, and disease characteristics associated with pain and fatigue using the Edmonton Symptom Assessment Scale (ESAS). Methods: We identified all patients diagnosed with non-metastatic breast cancer from 2011 Jan-2017 Jun at the Odette Cancer Centre with at least one ESAS completed pre- and post-RT. Data on systemic treatment, RT, demographics, and disease stage were extracted. To identify factors associated with pain and fatigue pre- and post-RT and their changes, univariate and multivariable linear regression analysis was conducted. p < 0.05 was considered statistically significant. Results: This study included 1222 female patients (mean age 59 years old) who completed ESAS on average 28- and 142-days pre-RT (baseline) and post-RT respectively. In multivariable analysis, higher baseline pain scores associated with adjuvant chemotherapy (p < 0.001) and eventual receipt of locoregional (p = 0.026) or chest wall RT (p = 0.003), whereas higher baseline fatigue scores associated with higher disease stages (p = 0.001) and locoregional RT (p < 0.001). Post-RT symptom severity correlated only with locoregional RT (higher pain scores, p < 0.001). Reductions in pain was associated with adjuvant chemotherapy (p = 0.002) and chest wall RT (p = 0.031). Reduction in fatigue was associated with adjuvant chemotherapy (p = 0.011) and locoregional RT (p = 0.007) although both had higher pre-RT scores in univariate analysis. Conclusions: Patients at higher disease stages or who received chemotherapy or chest wall RT tended to experience more severe short-term morbidity. However, patients who received locoregional RT tended to have greater pain that persisted after RT completion compared to those who did not.

Up to 20% of malignant phyllodes tumors (PT) metastasize, most frequently to the lungs, bone, and brain. Descriptions of metastatic PT are limited in the literature. In this series, we present three cases of malignant PT metastatic to various unusual sites including the peritoneum, soft tissue of the thigh, and scalp. All three patients initially received surgical resections, and two underwent adjuvant radiation. All three patients developed lung metastases first. Several palliative modalities were used including surgical resection, gamma-knife stereotactic radiosurgery, external beam radiation, and chemotherapy. All three patients died within 3 years of the initial diagnosis.