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BACKGROUND: There are no established threshold values regarding the degree of growth on imaging when assessing response of spinal metastases treated with stereotactic body radiation therapy (SBRT). OBJECTIVE: To determine a magnetic resonance imaging-based minimum detectable difference (MDD) in gross tumor volume (GTV) and its association with 1-yr radiation site-specific (RSS) progression-free survival (PFS). METHODS: GTVs at baseline and first 2 post-SBRT scans (Post1 and Post2, respectively) for 142 spinal segments were contoured, and percentage volume change between scans calculated. One-year RSS PFS was acquired from medical records. The MDD was determined. The MDD was compared against optimal thresholds of GTV changes associated with 1-yr RSS PFS using Youden's J index, and receiver operating characteristic curves between timepoints compared to determine which timeframe had the best association. RESULTS: A total of 17 of the 142 segments demonstrated progression. The MDD was 10.9%. Baseline-Post2 demonstrated the best performance (area under the curve [AUC] 0.90). Only Baseline-Post2 had an optimal threshold > MDD at 14.7%. Due to large distribution of GTVs, volumes were split into tertiles. Small tumors (GTV 8.3 cc) had 2 timepoints where optimal thresholds > MDD: Baseline-Post2 (13.3%; AUC 0.97) and Post1-Post2 (11.8%; AUC 0.66). Baseline-Post2 had the best association with RSS PFS for all tertiles. CONCLUSION: Given a MDD of 10.9%, for small GTVs, larger (>37%) changes were required before local failure could be determined, compared to 11% to 13% for medium/large tumors.

Technology increasingly mediates our everyday interactions with food, ranging from its production and handling to the experience of preparing and eating it with friends and family. However, it is unclear whether these technologies support decisions conducive to a healthy diet. In this work, we devised the first heuristics for evaluating a technology’s support for food literacy: the interconnected combination of awareness, knowledge, and skills to empower individuals to make informed food choices. We applied an iterative, expert-driven process to derive and refine our heuristics, starting with an established food literacy framework. We then conducted evaluations with Nutrition and HCI experts to show how the heuristics support summative and formative design and evaluations of food-related technologies. We show that the heuristics are valuable design tools, and that they help participants reflect on food literacy challenges. We also discuss tensions between nutrition and HCI best practices.

Background and PurposeChronic hydrocephalus may develop as a sequela of aneurysmal subarachnoid hemorrhage, requiring long-term cerebrospinal fluid shunting. Several clinical predictors of chronic hydrocephalus and shunt dependence have been proposed. However, no anatomical predictors have been identified.Materials and MethodsA retrospective cohort study was performed including 61 patients with aneurysmal subarachnoid hemorrhage. Clinical characteristics were noted for each patient including presentation World Federation of Neurosurgical Societies grade, modified Fischer grade, aneurysm characteristics, requirement for acute and chronic cerebrospinal fluid diversion, and 3-month modified Rankin scale. CT images were evaluated to determine the Evans’ index and to enumerate the number of arachnoid granulations. Association between the clinical characteristics with ventriculoperitoneal shunt insertion and the 3-month modified Rankin scale were assessed.ResultsThe initial Evans’ index was positively associated with mFisher grade and age, but not the number of arachnoid granulations. 16.4 % patients required insertion of a ventriculoperitoneal shunt. The number of arachnoid granulations were a significant negative predictor of ventriculoperitoneal shunt insertion [OR: 0.251 (95% CI:0.073-0.862; P=0.028)]. There was significant difference in the number of arachnoid granulations between those with and without ventriculoperitoneal shunt (p=0.002). No patient with greater than 4 arachnoid granulations required a ventriculoperitoneal shunt, irrespective of severity of initial grade.ConclusionArachnoid granulations may be protective against the development of shunt dependent chronic hydrocephalus after aneurysmal subarachnoid hemorrhage. This is irrespective of presenting hemorrhage severity. This is a potentially novel radiologic biomarker and anatomic predictor of shunt dependence.

The method of localized harmonic motion (LHM) monitoring has been proposed as an ultrasound-based monitoring technique for in vivo real-time ultrasound-guidance during thermal surgery. Objective: The focus of this paper is to study the performance of LHM monitoring in vivo in order to assess the tissue coagulation during ultrasound surgery of bone metastases. This is done through a pre-clinical study on large scale animals (pigs) as well as a first-in-human pilot study, using a hand held ultrasound-guided HIFU phased array. Methods: A flat, fully steerable HIFU phased array system (1024 elements, 100 mm diameter, 516 kHz), in combination with a co-aligned 64 element imaging system, is used to perform thermal surgery and monitor tissue coagulation using the LHM technique. The in vivo experiments are conducted using thirteen animals, followed by a first-in-human pilot study in which nine patients are enrolled. Results: The pre-clinical results show that the LHM monitoring method is able to detect about 80% of the observed coagulated tissue volumes visible in dissection. In the pilot study, six out of nine patients have durable pain reduction with good correlation observed from LHM detections. Conclusion: In general, the results suggest that the LHM monitoring performance is promising in detecting thermal tissue coagulation during focused ultrasound surgery in tissues close to the bone. Significance: The LHM technique can offer a very accessible and cost-efficient monitoring solution during ultrasound surgery within a clinical setting.

Background Stereotactic radiotherapy (SBRT) might improve pain and local control in patients with bone metastases compared to conventional radiotherapy, although an overall estimate of these outcomes is currently unknown. Methods A systematic review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pubmed, Embase, and Cochrane databases were systematically searched to identify studies reporting pain response and local control among patients with bone metastases from solid-organ tumors who underwent SBRT in 1–6 fractions. All studies prior to April 15, 2017, were included. Study quality was assessed by predefined criteria, and pain response and local control rates were extracted. Results A total of 2619 studies were screened; 57 were included (reporting outcomes for 3995 patients) of which 38 reported pain response and 45 local control rates. Local control rates were high with pain response rates above those previously reported for conventional radiotherapy. Marked heterogeneity in study populations and delivered treatments were identified such that quantitative synthesis was not appropriate. Reported toxicity was limited. Of the pain response studies, 73.7% used a retrospective cohort design and only 10.5% used the international consensus endpoint definitions of pain response. The median survival within the included studies ranged from 8 to 30.4 months, suggesting a high risk of selection bias in the included observational studies. Conclusions This review demonstrates the potential benefit of SBRT over conventional palliative radiotherapy in improving pain due to bone metastases. Given the methodological limitations of the published literature, however, large randomized trials are now urgently required to better quantify this benefit.

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.

Patients with multiple brain metastases may be treated with whole-brain radiation therapy (WBRT). For these patients, symptom palliation and improvement of quality of life (QOL) and performance status is of the upmost importance. The objective of the present study was to determine the symptom experience and overall QOL in patients with brain metastases before and after WBRT. A total of 14 symptom scores and overall QOL were collected prospectively in 217 patients for up to 3 months. Wilcoxon signed rank test was applied to determine significant symptoms and QOL changes. Spearman’s correlations were applied to determine the relationship between symptom scores and QOL. Appetite loss, weakness, and nausea significantly increased from baseline, while balance, headache, and anxiety significantly decreased from baseline. At baseline, all symptoms other than coordination were significantly correlated with QOL. At 1-month follow-up (FU), changes in concentration, weakness, coordination, and balance were significantly associated with QOL changes. At 2-month FU, changes in pain, insomnia, concentration, balance, and depression were significantly associated with QOL changes. At 3-month FU, only change in nausea was significantly associated with QOL changes. Following WBRT, certain symptoms may influence overall QOL to a greater extent than others, which may fluctuate with time.

The purpose of this study was to determine the incidence of pain flare (PF) in patients receiving spine stereotactic body radiotherapy (SBRT) treated with prophylactic oral dexamethasone (DEX) 1 h before and for 4 days following SBRT. Forty-seven patients were accrued on this prospective observational study. The first cohort of 24 patients was treated with 4 mg, while a second cohort of 23 patients treated with 8 mg of DEX. The Brief Pain Inventory (BPI) was used to score pain and functional interference each day during SBRT and for 10 days following. Comparisons between the 4 and 8 mg cohorts, in addition to our previously reported steroid naive patients post SBRT (n = 41), were also performed. The total incidence of PF was 19 % (9/47). The incidence in the 4 and 8 mg cohorts was 25 % (6/24) and 13 % (3/23), respectively, and the difference was not statistically significant (p = 0.46). Comparing functional interference, the 4 mg cohort had better profile in walking ability (p

SUMMARY Objective: To test the reliability, clinical and psychometric validity of the Brain Symptom and Impact Questionnaire (BASIQ) in patients with brain metastases. Methods: Brain metastases patients were interviewed using the BASIQ, Functional Assessment of Cancer-Brain (FACT-Br) and FACT-General (FACT-G) at baseline, with a follow-up assessment at 1 month. Results: Forty patients had complete one data and the median age was 64 years. Patients with higher KPS, ECOG of 2, primary breast cancer, or >3 brain metastases, scored higher on the symptom scale of the BASIQ. All subscales showed no significant change in patient symptoms from baseline to follow-up. Conclusion: This study supports that the reliability, clinical and psychometric validity of BASIQ to be used in brain metastases patients.

The purpose of this study was to examine changes in fatigue scores for patients receiving radiation therapy for bone metastases and its impact on quality of life (QOL). Fatigue and QOL scores were prospectively collected in patients for up to 3 months following radiation therapy for bone metastases using three questionnaires: group 1, Edmonton Symptom Assessment System (ESAS) (0–10); group 2, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30); and Core 15 Palliative (EORTC QLQ-C15-PAL) (1–4). Average fatigue score in group 1 (399 patients) was 4.72 at baseline, 5.08 at month 1, 5.01 at month 2, and 4.95 at month 3, and was 2.40, 2.39, 2.56, and 2.70 in group 2 (482 patients), respectively. Thirty-five percent of patients in group 1 had fatigue score increase ≥2 points at month 1, 36 % at month 2, and 36 % at month 3. Twenty-one percent of patients in group 2 had fatigue score increase ≥1 at month 1, 27 % at month 2, and 40 % at month 3. There was a statistically significant increase in fatigue score from baseline to all 3 months in group 1 only. In both groups, there was a highly significant negative correlation between fatigue and overall QOL scores at baseline and any follow-up month. There was a statistically significant worsening in fatigue in group 1 only. Up to one third had increased fatigue of clinical significance. Patients with less fatigue symptoms reported better overall QOL.

Aim: The present study aimed to determine the prognostic survival value of pretreatment health-related quality of life (HRQOL) and changes in HRQOL following whole-brain radiation treatment in patients with brain metastases. Methods: Patients who were treated with whole-brain radiation treatment and completed HRQOL questionnaires were included. Univariate and multivariate Cox proportional hazard models of overall survival (OS) were conducted for overall HRQOL and domain scores. Results & conclusion: Patients with lower HRQOL at baseline, especially lower physical functioning and motor dysfunction domains, were more likely to have poorer survival. Changes in overall HRQOL and its domains were not significantly related to OS. Pretreatment HRQOL, especially physical functioning and motor dysfunction, has added prognostic value in patients with brain metastases.

Introduction Following surgery, the formation of heterotopic ossification (HTO) can limit mobility and impair quality of life. Radiotherapy has been proven to provide efficacious prophylaxis against HTO, especially in high-risk settings. Purpose The current review aims to determine the factors influencing HTO formation in patients receiving prophylactic radiotherapy. Methods A systematic search of the literature was conducted on Ovid Medline, Embase and the Cochrane Central Register of Controlled Trials. Studies were included if they reported the percentage of sites developing heterotopic ossification after receiving a specified dose of prophylactic radiotherapy. Weighted linear regression analysis was conducted for continuous or categorical predictors. Results Extracted from 61 articles, a total of 5464 treatment sites were included, spanning 85 separate study arms. Most sites were from the hip (97.7%), from United States patients (55.2%), and had radiation prescribed postoperatively (61.6%) at a dose of 700cGy (61.0%). After adjusting for radiation site, there was no statistically significant relationship between the percentage of sites developing HTO and radiation dose ( p =0.1) or whether radiation was administered preoperatively or postoperatively ( p =0.1). Sites with previous HTO formation were more likely to develop recurrent HTO than those without previous HTO formation ( p =0.04). There was a statistically significant negative relationship between the HTO development and the cohort mean year of treatment ( p =0.007). Conclusion Decreases in rates of HTO over time in this patient population may be a function of more efficacious surgical regimens and prophylactic radiotherapy.

Quality of life (QoL) assessment questionnaires can be burdensome to advanced cancer patients, thus necessitating the need for shorter assessment instruments than traditionally available. We compare three shortened QoL questionnaires in regards to their characteristics, validity, and reliability.A literature search was conducted to identify studies that employed or discussed three abridged QoL questionnaires: the European Organization for Research and Treatment of Cancer Quality of Life Core 15-Palliative Care (EORTC QLQ-C15-PAL), the Functional Assessment of Cancer Therapy-General-7 (FACT-G7), and the Functional Assessment of Chronic Illness Therapy-Palliative Care-14 (FACIT-PAL-14). Articles that discussed questionnaire length, intended use, scoring procedure, and validation were included.The 7-item FACT-G7 is the shortest instrument, whereas the EORTC QLQ-C15-PAL and the FACIT-PAL-14 contain 14 and 15 items, respectively. All three questionnaires have similar recall period, item organization, and subscale components. Designed as core questionnaires, all three maintain content and concurrent validity of their unabridged original questionnaires. Both the EORTC QLQ-C15-PAL and the FACT-G7 demonstrate good internal consistency and reliability, with Cronbach's α ≥0.7 deemed acceptable. The developmental study for the FACIT-PAL-14 was published in 2013 and subsequent validation studies are not yet available.The EORTC QLQ-C15-PAL and the FACT-G7 were found to be reliable and appropriate for assessing health-related QoL issues-the former for palliative cancer patients and the latter for advanced cancer patients receiving chemotherapy. Conceptually, the FACIT-PAL-14 holds promise to cover social and emotional support issues that are not completely addressed by the other two questionnaires; however, further validation is needed.

This review compares and contrasts the development, validity, and characteristics of two quality of life (QOL) assessment tools used in patients with primary brain cancers: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Brain Cancer Module (EORTC QLQ-BN20) and the Functional Assessment of Cancer Therapy-Brain (FACT-Br).A literature search was conducted using the Cochrane Central Register of Controlled Trials (June 2013), Ovid EMBASE (1947 to 2013, week 27), and Ovid MEDLINE (1946 to July 2013, week 1) to identify studies that discussed the development, characteristics, validity, and reliability of the EORTC QLQ-BN20 or the FACT-Br.The EORTC QLQ-BN20 consists of 20 items that assess future uncertainty, visual disorder, motor dysfunction, and communication deficit. Items are presented as questions on a scale ranging from 1 = “not at all” to 4 = “very much.” Reliability and validity testing of the QLQ-BN20 revealed a Cronbach’s alpha coefficient that ranged from 0.71 to 0.90. The FACT-Br consists of 23 items that assess general well-being and brain cancer-specific concerns that include concentration, memory, seizures, eyesight, hearing, speech, personality, expression of thoughts, weakness, coordination, and headaches. These items are presented as statements on a scale ranging from 0 = “not applicable” to 4 = “extremely relevant.” The FACT-Br underwent validity as well as test-retest reliability testing with 101 and 46 patients, respectively. Validity testing found low to moderate correlation with the FACT-G questionnaire, while reliability testing for the brain subscale revealed an acceptable correlation coefficient (r = 0.66; p 0.001).The QLQ-BN20 and the FACT-Br are both valid and reliable tools that have been used extensively in the primary brain cancer population. Choice between the two tools should consider each instrument’s individual strengths and weaknesses.

Objective: Radiation therapy can often be used for palliation of thoracic symptoms in patients presenting with locally advanced lung cancer or lung metastases. The aim of this study was to examine whether patterns of practice in prescription of palliative thoracic radiation therapy have changed over time in the Rapid Response Radiotherapy Program. Secondary outcomes were factors that may have influenced the treatment regimen prescribed, including patient, disease, and organisational factors. Methods: This study was a retrospective review of a prospective database of patients with locally advanced lung cancer or lung metastases referred to the Rapid Response Radiotherapy Program for thoracic symptoms between 1 July 2006 and 30 April 2012. Patient demographics, and organisational and disease factors were descriptively analysed. Differences in proportions between unordered categorical variables were examined using chi-squared test. Univariate logistic regression analysis and backward stepwise selection procedure were used to determine the most significant factors in prescription practice. Results: A total of 175 courses of palliative thoracic radiation therapy were prescribed. The median age of the patients was 71 years, and the median Karnofsky Performance Status was 60. The most commonly prescribed treatment regimen was 20 Gy in 5 fractions (20 Gy/5), which made up 64% of all the courses prescribed. There was a significant increase in frequency of the prescription of 20 Gy/5 over time (p = 0.02). The site of radiation (disease factor) and years of certification for independent practice of the treating radiation oncologist (organisational factor) were also significant factors in the prescription of 20 Gy/5 over time (both p = 0.02). Conclusion: A significant increase in the prescription of 20 Gy/5 was observed over time. However, the prescription of a higher dose fractionation schedule for patients with a higher performance status, as seen in other clinical trials and guidelines, was not observed. Future studies should further explore other possible factors such as patient survival, preference, comorbidities, and disease burden that may influence the dose fractionation prescribed.

We examined whether patterns of practice in the prescription of palliative radiation therapy for bone metastases had changed over time in the Rapid Response Radiotherapy Program (rrrp). After reviewing data from August 1, 2005, to April 30, 2012, we analyzed patient demographics, diseases, organizational factors, and possible reasons for the prescription of various radiotherapy fractionation schedules. The chi-square test was used to detect differences in proportions between unordered categorical variables. Univariate logistic regression analysis and the simple Fisher exact test were also used to determine the factors most significant to choice of dose&ndash, fractionation schedule. During the study period, 2549 courses of radiation therapy were prescribed. In 65% of cases, a single fraction of radiation therapy was prescribed, and in 35% of cases, multiple fractions were prescribed. A single fraction of radiation therapy was more frequently prescribed when patients were older, had a prior history of radiation, or had a prostate primary, and when the radiation oncologist had qualified before 1990. For patients with bone metastasis, a single fraction of radiation therapy was prescribed with significantly greater frequency.

Assessment of health-related quality of life (HRQOL) is critical to effective delivery of palliative care in patients with advanced cancer. The current study analyzes relationships between baseline social determinants of health and medical factors, and self-reported HRQOL in patients with bone metastases receiving palliative radiotherapy.Advanced cancer patients referred for radiotherapy treatment of bone metastases completed the EORTC QLQ-C30 questionnaire in multiple outpatient clinics internationally. Demographics and social determinants were collected as baseline information. Univariate and Bonferroni-adjusted multivariate linear regression analyses were used to detect significant correlations between baseline determinants and different HRQOL domains.Karnofsky Performance Status (KPS) was correlated with better physical (p = 0.0002), role (p 0.0001), emotional (p 0.0001), and social (p 0.0001) functioning, and global health scores (p = 0.0015) and predicted lower symptom scores for fatigue (p 0.0001), pain (p 0.0001), appetite loss (p 0.0001), and constipation (p 0.0001). Increased age was predictive of better social functioning (p 0.0001) and less insomnia (p = 0.0036), higher education correlated with better global health status (p = 0.0043), and patients who were employed or retired had improved physical functioning (p = 0.0004 and p = 0.0030, respectively) and less financial challenges compared to patients who were unemployed (p = 0.0005).Baseline KPS had the greatest influence on EORTC QLQ-C30 domain scores. Age, education level, and employment status had significant impacts, although on fewer domains. Further studies that investigate baseline determinants are worthwhile to clarify relationships in order to care for patients more effectively at the end of life.

Objective: We set out to review the Rapid Response Radiotherapy Program (rrrp). Methods: We retrospectively reviewed a prospective database of patients referred to the rrrp between August 1, 2008, and June 30, 2012, extracting patient demographics, case dispositions, and wait times in days from referral to consultation and from consultation to treatment. Results: Of 2742 patients referred to the rrrp, 1458 (53%) were men, and 1284 (47%) were women. Median age was 64 years. The most prevalent primary cancer sites were lung (33%), breast (21%), and prostate (17%). The most common reasons for referral were bone metastases (53%) and brain metastases (21%). Palliative radiation therapy was given to 1890 patients. The median wait time from referral to consultation was 3 days. Among treated patients, 60% were treated on the day of their consultation, and 33%, within 1–6 days. Conclusions: The rrrp continues to deliver timely palliative radiation therapy to patients, comparable to earlier reviews. The continued success of the rrrp will remain a model for future rapid-access palliative radiation therapy clinics.

To conduct a systematic review on validated instruments used to assess quality of life (QOL) in patients with either primary or metastatic lung neoplasms. A literature search was conducted through the Embase (1950 - 2012 week 30) and Medline (1946 - 2012 week 3 July) databases. All compiled studies utilized QOL or symptom palliation as a primary or secondary outcome for patients with advanced lung cancer. A total of 17 studies met our criteria. Four questionnaires were most commonly used: the EORTC QLQ-C-30, the EORTC QLQ-LC-13, the Rotterdam Symptom Check-list (RSCL), and the Hospital Anxiety and Depression Scale (HADS). The limited number of studies assessing QOL in patients with advanced lung cancer suggests that QOL is still an uncommon endpoint for this patient population. Nine of seventeen (53%) studies evaluated QOL in their cohorts and out of those nine, seven (77%) included the use of a lung-specific tool. In total there were eleven of seventeen (65%) studies that evaluated symptom palliation, indicating the relevance of symptom palliation as an endpoint in this population. It is encouraged that lung specific QOL questionnaires, such as the FACT-L and the EORTC QLQ LC-13, be used in tandem with general questionnaires, such as the FACT-G and the EORTC QLQ C-30, in advanced lung cancer patients undergoing radiotherapy. Clinicians should also be advised to focus more on QOL assessment.

INTRODUCTION: Advanced cancer patients are multi-symptomatic and require attentive palliative care. As gender differences are apparent in multiple aspect of everyday life, this literature review aims to determine the gender differences seen in the population of advanced cancer patients and the symptoms that they experience. METHODS: A literature review was conducted using the OvidSP Medline database from 1946 to November 2012. Randomized, prospective or retrospective cohort studies on advanced cancer patients who were undergoing any type of palliative treatments (palliative radiation, chemotherapy) or those in which palliative treatments have failed (antalgic treatment) were included. The patient population, tools/questionnaire used and gender differences in symptoms found statistically or qualitatively significant in the respective studies were extracted. RESULTS: Of the 163 studies resulting from the literature search, nineteen publications were identified. Gender differences in multiple symptoms were discovered. Gender differences were commonly found in symptoms of emotional changes, fatigue, gastrointestinal symptoms (nausea, vomiting, and diarrhea) anxiety, tension, sleep problems and pain. CONCLUSION: At present, gender differences seen in the symptoms experienced by advanced cancer patients continues to be inconclusive. Further study investigating gender differences in the symptoms experienced by advanced cancer patients as the primary endpoint is recommended.

Re-irradiation of painful bony metastases is increasingly performed since patients are receiving better systemic treatments and having longer life expectancy, and may also be due to the increase use of initial single fraction radiotherapy. However, randomized control trial on the efficacy of re-irradiation is lacking. A recent meta-analysis concluded with a 58% response rate for pain relief by re-irradiation of symptomatic bone metastases. In this review, the effectiveness of re-irradiation in terms of clinical and economical aspects, and clinical questions on who, when, and how to re-irradiate would be discussed. A brief review of other treatment options and comparison with re-irradiation of bone metastases would be performed.

Background: Having a clear prognosis for patients with brain metastases allows health care practitioners (HCPs) to determine appropriate palliative management and assist patients when making informed treatment decisions. The objective of this study was to determine the prognostic significance of commonly experienced symptoms as well as their changes. Methods: Overall survival (OS) was calculated from the date of consultation for palliative radiotherapy to date of death or censored at last follow-up date. Symptom changes at follow up were defined as worsened, improved, or no change. Univariate and multivariate cox proportional hazard (PH) model of OS was conducted on 14 symptoms at baseline and on changes in those symptoms at 1-, 2-, and 3-month follow-ups. Results: From 1999 to 2013, 1,660 patients were included for baseline symptom analysis. Through univariate analysis, fatigue, nausea, appetite loss, coordination, concentration, balance and depression were significantly related to OS. Upon multivariate analysis, fatigue and appetite loss were most predictive of short survival. For symptom change, 201 patients were included. The actuarial median OS was 5.0 months [95% confidence interval (CI): 4.3–7.0], 7.1 months (95% CI: 5.2–9.5) and 8.8 months (95% CI: 5.8–11.5) for patients with month 1, 2, and 3 follow-ups, respectively. The most common symptom changes following whole brain radiotherapy (WBRT) were: worsened fatigue, appetite loss, and weakness. Worsened difficulty concentrating, fatigue, nausea and headaches were most predictive of a poorer survival outcome. Conclusions: HCPs should be aware of the shorter prognosis associated with patients exhibiting one or more of these symptoms and tailor care accordingly to maximize patients’ remaining quality of life (QOL).

The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting&ndash, specific daily diary, the Functional Living Index&ndash, Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire&ndash, C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. &ldquo, Overall control&rdquo, was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. &ldquo, Acute phase&rdquo, was defined as the days during radiation until the first day after radiation, &ldquo, delayed phase&rdquo, was defined as days 2&ndash, 10 after radiation. The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively, during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%, during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires. Ondansetron rdf is effective for the prophylaxis of rinv.

In 1996, the Toronto Sunnybrook Regional Cancer Centre developed the Rapid Response Radiotherapy Program (RRRP). The objective of this clinic is to consult, simulate, plan, and treat patients with palliative radiotherapy on the same day. In 2004, the RRRP initiated a program to provide clinical and research experience to undergraduate students interested in health sciences. The purpose of this study is to review the 10-year (2004-2013) experience of the RRRP and to examine whether the goals of the student program have been met. Students who worked in the RRRP from 2004 to 2013 were contacted to complete a short survey regarding their overall experience with the program and their current endeavors. Student accomplishments were collected from an internal database as well as PubMed. Descriptive statistics were used to analyze results. A total of 54 students from ten postsecondary institutions have worked in the RRRP; 29 were from the University of Waterloo undergraduate co-op program. In total, 214 articles with first authorship from students were published, 93 (43%) of which can be found on PubMed. Other accomplishments include 40 book chapters, 58 invited presentations, and 99 awards cumulatively. Qualitative data regarding student perspectives of their experience in the RRRP were also analyzed. Over the past 10 years, the RRRP has achieved its goal of providing quality medical and research experience to students interested in the health sciences. Using the responses of past and present students, we hope to continue to shape our program and provide unique opportunities to future students.

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.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.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.The high internal consistency at all timepoints indicates that the FLIE QOL instrument is useful for the RINV population.

SUMMARY Objective: To validate the Brain Symptom and Impact Questionnaire (BASIQ) version 1.0 for brain metastases. Methods: Patients with brain metastases and their healthcare professionals (HCPs) assessed the relevance of the BASIQ on a 0–10 scale with 10 as extremely relevant. Results: A total of 52 patients and 20 HCPs participated in this study. In total, 95% of HCPs and 85% of patients found all items relevant. Balance and walking ability were rated relevant by 100% of patients and HCPs. Headache, nausea, energy, memory and ability to do housework were also rated relevant by 100% of HCPs. Over 95% of patients determined the items of ability to do housework, tiredness, energy, vision, memory and putting ideas into words as relevant. There were no items rated below 7 by patients or below 5 by HCPs. Conclusion: This study indicates that BASIQ version 1.0 has valid content items encompassing disease-related symptom and impact on daily living.

Breakthrough cancer pain is defined as a transient exacerbation of pain that occurs spontaneously or in response to a trigger, despite stable and controlled background pain. Breakthrough pain often causes significant functional impairments for patients and can decrease quality of life. The objective of the study was to determine differences between breakthrough cancer pain incidence and management in Canada and Europe. Data collected from previous studies of breakthrough cancer pain in Canada and Europe was compared. A standard survey with identical inclusion/exclusion criteria was utilized for both patient populations. Both groups of patients had a similar number and duration of breakthrough pain episodes, and similar pain intensity and pain interference with their daily activities. European patients reported better analgesic efficacy and satisfaction with management, and a greater percentage of European patients were prescribed a transmucosal fentanyl formulation (19.1 vs 2.9 %). More European patients (55 %) than Canadian patients (32.5 %) took their rescue medication every time they had a breakthrough pain episode. Breakthrough cancer pain in both Canadian and European patients greatly impacts their daily living, and both groups of patients had similar experiences with breakthrough cancer pain. Currently, this pain is not adequately managed for many patients. The role for new analgesic treatments in management of breakthrough cancer pain needs further study.

Aim: The purpose of this review was to investigate if advances in bone-targeted therapies have decreased the incidence of skeletal morbidity rates over time in patients with multiple myeloma-related bone disease. Methods: A literature search was conducted over the OvidSP platform in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify Phase III results from bone-targeted therapy trials in patients with multiple myeloma. The skeletal morbidity rate was the end point of interest, and for each study, a mean year of enrollment ([start of enrollment + end of enrollment]/2) was calculated. Results: A total of eight study arms were identified, with only two placebo arms; therefore, a weighted linear regression was not feasible and only intervention treatment arms were analyzed. A statistically significant downward trend in the skeletal morbidity rate was observed in all intervention arms. Conclusion: The incidence of skeletal morbidity rates has decreased significantly over time in patients with multiple myeloma.

Aims: The objective of this study is to compare adverse events experienced among different bone-modifying agents. Methods: A literature search was conducted to identify Phase III bisphosphonate and bone-modifying agent trials reporting adverse effects. Thirty-seven adverse events of interest were identified for six different treatment options. Weighted linear regression modeling was performed on the adverse event proportions with treatment groups, normalized through applying natural log transformations. Results: There were significant differences in adverse events of vomiting (p = 0.045) and osteonecrosis of the jaw (p = 0.017), and combined item events of nausea/vomiting (p = 0.048), hematological and lymphatic system toxicities (p = 0.020), and any respiratory system problem (p = 0.023) between bone-modifying agent and placebo trials. The significant toxicities were observed even after adjusting for the two confounding factors of age and primary cancer site. Conclusion: While adverse effects are consistently experienced more frequently in patients receiving bone-modifying agents when compared with placebos, we find that the majority of individual side effects are not significantly more frequent in patients receiving bone-modifying agents compared with placebo.

Cancer rates are increasing, with the majority of cancer patients being over the age of 65. As the global population ages and life expectancies increase, the number of elderly patients requiring treatment also increases, thus the added challenges of treating elderly patients need to be addressed. This chapter outlines the challenges of palliative radiotherapy for elderly patients with bone metastases. We will begin with defining the term elderly, and outline the recent demographic details of patients with cancer. An update on the current status of elderly patients in clinical trials and discussion of factors that may affect enrolment of these patients into trials will be given. With an emphasis on palliative clinical trials, we will discuss methods to promote accrual of elderly patients in this setting. A review of the safety and efficacy of treatment in the elderly is also given, and palliative radiotherapy for the treatment of elderly patients with bone metastases is determined to be an advisable treatment and should be recommended to patients regardless of age. Physical burden of treatment in elderly patients can be alleviated by hypofractionated treatments, as multiple trials and meta-analyses have demonstrated their equivalence in pain control. In elderly patients, palliative radiotherapy may be more beneficial than other treatment options, as opioid-related adverse events are greater in this population. Physicians should continue to encourage elderly participation in clinical trials as this data forms the basis of treatment guidelines. Radiation oncologists are encouraged to offer elderly patients single treatments for bone metastases to reduce the physical burden of multiple treatments.

The purpose of this review was to determine the efficacy of re-irradiation in patients with bone metastases. A literature search was conducted in Ovid Medline, OldMedline, Embase, Embase Classic, and Cochrane Central Register of Controlled Trials using relevant subject headings and keywords such as bone metastases, radiotherapy and palliative care. The resulting articles were sorted for inclusion for palliative external beam radiation retreatment response rate data. The literature search produced 2164 references and 15 articles were included in the final selection. Complete, partial and overall response rates were calculated to be 20%, 50% and 68%, respectively. Information on treatment toxicities was scarce. The efficacy of re-irradiation is comparable to initial radiation treatment. However, aspects of re-irradiation treatment including dose fractionation, related adverse events and toxicities require further corroboration.

Health related quality of life (HRQOL) is a multidimensional concept that is especially important for cancer patients with bone metastases, as maintaining and improving HRQOL is often the main focus of treatment. This study aims to determine factors that may influence HRQOL, which may in turn influence treatment and care of patients.Patients (n=396) completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Bone Metastases module (BM22) at baseline. The EORTC QLQ-BM22 consists of four scales: painful site (PS), pain characteristics (PC), functional interference (FI), and psychosocial aspect (PA) scales. EORTC QLQ-BM22 data, together with sociodemographic and medical factors were analyzed by univariate analysis of variance (ANOVA). Items of significance were determined through backward selection, which were then put through multivariate analysis to determine further significance.Through ANOVA analysis, KPS80 and breast primary histology were predictive of better HRQOL in the PS scale, while KPS80, female gender, and breast primary histology were predictive of better HRQOL in the PC and FI scales. KPS80 and prostate primary histology were predictive of better HRQOL in the PA scale. KPS80 and primary cancer site were confirmed as significant predictive factors in multivariate analysis.This study identified baseline factors of gender, performance status, and primary histology as determinants of HRQOL in patients with bone metastases. Further study focusing on current treatment (chemotherapy, bisphosphonates, and radiotherapy) and spiritual well-being may identify additional factors affecting HRQOL. Understanding the influence of these factors will allow health care professionals to provide more effective palliative care.

The brief pain inventory (BPI) is often used to assess pain and functional interference as a result of pain in cancer patients. Minor improvements or deteriorations in BPI may be statistically significant due to large sample sizes but may not necessarily be clinically relevant. The purpose of this study was to determine the minimal clinically important differences (MCID) in the functional BPI in patients with pain due to bone metastases.BPI scores were collected from patients with painful bone metastases who visited the Rapid Response Radiotherapy Program for palliative radiotherapy. Pain and functional interferences scores were also collected monthly for three months. Patients were categorized into "complete or partial response," "pain progression," and "indeterminate response" based on their pain scores as recommended by the latest consensus definitions. Anchor-based determination of MCIDs of functional interference scores was calculated by determining the difference between the mean follow-up scores and the mean baseline scores for patients from each of the three response groups. Distribution-based estimates were obtained utilizing 0.2, 0.3, and 0.5 standard deviation (SD) effect sizes and the standard error of measurement. The anchor-based method results were compared with the distribution-based method results.Statistically significant MCIDs were determined for all of the functional interference items of BPI for patients with "complete or partial response"; whereas, no statistically significant MCIDs in BPI scores could be determined for patients with "pain progression." Some of the functional interference items of BPI had statistically significant MCIDs for patients with "indeterminate response," although these were generally smaller than patients with complete or partial response. Using the distribution-based approach, an effect size of 0.5 SD was the closest estimate for determining the MCID for both patients with complete or partial response and those with indeterminate response.The MCIDs determined for pain improvement were rather large, where as statistically significant MCIDs could not be detected for pain deterioration. Knowledge of MCIDs utilizing the BPI will allow physicians to evaluate the impact of treatment (or no treatment) on a patient's functional abilities. Knowledge of MCIDs may allow for sample size determination in future clinical trials.

Aims Skeletal-related events (SREs) in patients with bone metastases decrease a patient's quality of life and functional status. Although bone-modifying agents have been found to reduce the time to first on-trial SRE and decrease the total incidence of SREs in randomised clinical trials, standard practice in the management of bone metastases has changed concurrently. The purpose of this study was to investigate if advances in bone-targeted therapies have decreased the incidence of individual types of SREs and to delineate the trend of SREs. Materials and methods A literature review was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify phase III, randomised bisphosphonate and other bone-targeted therapy trials from 1980 to September 2011. For all studies, a mean year of enrolment ([start of enrolment + end of enrolment]/2) was calculated. The incidences of SREs were tabulated and expressed as percentages of on-trial patients. Generalised linear mixed models were used to search for the trends of SREs over time for all placebo and intervention arms. Regression coefficients were interpreted as the odds ratio, which was calculated using the exponential of the slope. Ninety-five per cent confidence intervals were also calculated. Results In total, 20 eligible studies were identified that reported SRE data from phase III trials, of which 11 were suitable for the quantitative analysis. Most of the articles included patients with breast cancer and the remaining involved patients with prostate, renal cell, bladder and lung cancer or other solid tumours. Enrolment periods for all included data ranged from 1990 to 2009. Statistically significant overall downward trends in pathological fractures and the need for surgery were seen over time. Also significant differences between intervention and placebo were seen with all SREs. Conclusion The decrease in SREs over time may not only be a result of the development of new generation bone-targeted agents, but also due to better systemic management and awareness of events associated with bone metastases.

anatomic site. Follow-up was completed on 55 patients (71%). Median follow-up time from the initial consult was 43 days (range, 31-77). The median Palliative Performance Status increased from 50 to 65 (p Z 0.97). The median patient reported overall health score, improved from 5 to 7 (p Z 0.07). Among patients who received chest RT, 88% reported stable or improved levels of shortness of breath following RTwith a median score of 3 prior to treatment, and 2 post-treatment (p Z 0.01) and 91% reported stable or better cough compared with a median baseline score of 2 and 1 post treatment (p Z 0.01). In patients who received RT for bone metastases, median pain scores decreased from 4 to 0.5 (pZ 0.01). Compared to baseline, bone pain was more likely to be relieved by an analgesic following RT (p Z 0.07) and less likely to interfere with sleep (p Z 0.03). Daily dexamethasone consumption decreased from 7 mg to 1.3 mg following whole brain RT (p < 0.01). The 3 and 6 month overall survival was 63% and 52%, respectively; median survival was not met at time of analysis. Conclusions: Despite the burden of symptoms that patients present with at consultation, the services provided by the clinic seemed to be associated with an improvement in patient reported outcomes. Overall health, respiratory symptoms and bony pain in particular seem to improve at follow-up. These positive findings, combined with prior evidence that the rapid access clinic improves the delivery of care to this patient group compared to standard practice, highlight the continued value of the clinic at our center and may provide support for extending this clinic model to other primary tumor sites. Author Disclosure: S. Lefresne: None. R.A. Olson: None. R. Cashman: None. W. Jiang: None. P. Kostuik: None. K. Levy: None. M. Liu: None. H. Carolan: None. M. Mckenzie: None. E. Berthelet: None.

Objective: To investigate the quality of life (QOL) following palliative radiotherapy for painful bone metastases. Methods: A literature search was conducted in OvidSP Medline (1946–Jan Week 4 2014), Embase (1947–Week 5 2014), and the Cochrane Central Register of Controlled Trials (Dec 2013) databases. The search was limited to English. Subject headings and keywords included ‘palliative radiation’, ‘cancer palliative therapy’, ‘bone metastases’, ‘quality of life’, and ‘pain’. All studies (prospective or retrospective) reporting change in QOL before and after palliative radiotherapy for painful bone metastases were included. Results: Eighteen articles were selected from a total of 1730. The most commonly used tool to evaluate QOL was the Brief Pain Inventory. Seventeen studies collected data prospectively. An improvement in symptoms and functional interference scores following radiotherapy was observed in all studies. The difference in changes in QOL between responders and non responders was inconsistently reported. Conclusion: QOL improves in patients who respond to palliative radiotherapy for painful bone metastases.