Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis.

Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results.

Clinical and laboratory factors associated with coronavirus disease 2019 (Covid-19): A systematic review and meta-analysis.

SARS Coronavirus-2 is one of the most widespread viruses globally during the 21st century, whose severity and ability to cause severe pneumonia and death vary. We performed a comprehensive systematic review of all studies that met our standardised criteria and then extracted data on the age, symptoms, and different treatments of Covid-19 patients and the prognosis of this disease during follow-up. Cases in this study were divided according to severity and death status and meta-analysed separately using raw mean and single proportion methods. We included 171 complete studies including 62,909 confirmed cases of Covid-19, of which 148 studies were meta-analysed. Symptoms clearly emerged in an escalating manner from mild-moderate symptoms, pneumonia, severe-critical to the group of non-survivors. Hypertension (Pooled proportion (PP): 0.48 [95% Confident interval (CI): 0.35-0.61]), diabetes (PP: 0.23 [95% CI: 0.16-0.33]) and smoking (PP: 0.12 [95% CI: 0.03-0.38]) were highest regarding pre-infection comorbidities in the non-survivor group. While acute respiratory distress syndrome (PP: 0.49 [95% CI: 0.29-0.78]), (PP: 0.63 [95% CI: 0.34-0.97]) remained one of the most common complications in the severe and death group respectively. Bilateral ground-glass opacification (PP: 0.68 [95% CI: 0.59-0.75]) was the most visible radiological image. The mortality rates estimated (PP: 0.11 [95% CI: 0.06-0.19]), (PP: 0.03 [95% CI: 0.01-0.05]), and (PP: 0.01 [95% CI: 0-0.3]) in severe-critical, pneumonia and mild-moderate groups respectively. This study can serve as a high evidence guideline for different clinical presentations of Covid-19, graded from mild to severe, and for special forms like pneumonia and death groups.

Cancer cachexia: molecular mechanism and pharmacological management.

Cancer cachexia often occurs in malignant tumors and is a multifactorial and complex symptom characterized by wasting of skeletal muscle and adipose tissue, resulting in weight loss, poor life quality and shorter survival. The pathogenic mechanism of cancer cachexia is complex, involving a variety of molecular substrates and signal pathways. Advancements in understanding the molecular mechanisms of cancer cachexia have provided a platform for the development of new targeted therapies. Although recent outcomes of early-phase trials have showed that several drugs presented an ideal curative effect, monotherapy cannot be entirely satisfactory in the treatment of cachexia-associated symptoms due to its complex and multifactorial pathogenesis. Therefore, the lack of definitive therapeutic strategies for cancer cachexia emphasizes the need to develop a better understanding of the underlying mechanisms. Increasing evidences show that the progression of cachexia is associated with metabolic alternations, which mainly include excessive energy expenditure, increased proteolysis and mitochondrial dysfunction. In this review, we provided an overview of the key mechanisms of cancer cachexia, with a major focus on muscle atrophy, adipose tissue wasting, anorexia and fatigue and updated the latest progress of pharmacological management of cancer cachexia, thereby further advancing the interventions that can counteract cancer cachexia.

Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary.

The spread of pandemic COVID-19 has created unprecedented need for information. The pandemic is the cause of significant mortality and with this the need for rapidly disseminated information for palliative care professionals regarding the prevalence of symptoms, their intensity, their resistance or susceptibility to symptom control and the mode of death for patients. METHODS: We undertook a systematic review of published evidence for symptoms in patients with COVID-19 (with a specific emphasis on symptoms at end of life) and on modes of death. Inclusion: prospective or retrospective studies detailing symptom presence and/or cause or mode of death from COVID-19. RESULTS: 12 papers met the inclusion criteria and gave details of symptom burden: four of these specifically in the dying and two detailed the cause or mode of death. Cough, breathlessness, fatigue and myalgia are significant symptoms in people hospitalised with COVID-19. Dyspnoea is the most significant symptom in the dying. The mode of death was described in two papers and is predominantly through respiratory or heart failure. CONCLUSIONS: There remains a dearth of information regarding symptom burden and mode of death to inform decisions regarding end-of-life care in patients dying with COVID-19. Rapid data gathering on the mode of death and the profile of symptoms in the dying and their prevalence and severity in areas where COVID-19 is prevalent will provide important intelligence for clinicians. This should be done urgently, within ethical norms and the practicalities of a public health, clinical and logistical emergency.

The association of cancer-related fatigue with all-cause mortality of colorectal and endometrial cancer survivors: Results from the population-based PROFILES registry.

PURPOSE: Cancer-related fatigue (CRF) is one of the most prevalent symptoms experienced by cancer survivors. However, researchers are only beginning to elucidate the risk factors, underlying mechanism(s), and its association with other outcomes. Research on the association between CRF and mortality is limited. METHODS: The study sample comprised 2059 short-term (<5 years postdiagnosis) cancer survivors from four PROFILES registry studies. Survivors diagnosed with stage I-III colorectal cancer (CRC) or stage I-III endometrial cancer (EC), with no evidence of disease, were identified and followed-up by the Netherlands Cancer Registry. Fatigue was assessed with the Fatigue Assessment Scale. Cox proportional hazards models adjusted for demographic, clinical, and lifestyle characteristics were performed to assess the association of CRF with all-cause mortality. Date of censoring was February 1, 2017. RESULTS: Prevalence of CRF varied between 35.8% (male CRC) and 43.6% (female CRC). After a median follow-up period of 9.0 years, a total of 408 survivors (20%) had died. CRF was associated with increased all-cause mortality in male CRC survivors (HRadj = 1.75, 95% CI [1.31-2.33]). This association remained statistically significant after excluding survivors experiencing anhedonia. For female CRC (HRadj = 1.32, 95% CI [0.90-1.97]) and EC (HRadj = 1.27, 95% CI [0.84-1.90]) survivors, there was no significant association with all-cause mortality for the fatigued group in multivariable analyses. CONCLUSION: Our study found that CRF is significantly associated with all-cause mortality in male CRC survivors, irrespective of potential confounders. This result suggests that clinicians should increase their attention towards the recognition and treatment of CRF.

Risk of fatigue in cancer patients treated with anti programmed cell death-1/anti programmed cell death ligand-1 agents: a systematic review and meta-analysis.

AIM: We aimed to assess the incidence and relative risk (RR) of fatigue in cancer patients treated with anti programmed cell death-1 (PD-1) and anti programmed cell death ligand-1 (PD-L1) agents. PATIENTS & METHODS: Eligible studies were selected according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Incidence, RR and 95% CIs were calculated using random or fixed-effects models. RESULTS: Thirty-eight studies were included in this analysis, with a total of 11,719 patients. The incidences were 23.4 and 2.1% for all- and high-grade fatigue, respectively. The highest incidence of high-grade fatigue was reported by the combination of nivolumab and ipilimumab. Overall RR of high-grade fatigue with anti-PD-1/PD-L1 compared with chemotherapy or targeted therapy was 0.48. CONCLUSION: Treatment with anti-PD-1/PD-L1 agents correlates with lower incidence and RR of fatigue compared with standard therapies.

Are older long term care residents accurately prognosticated and consequently informed about their prognosis? Results from SHELTER study data in 5 European countries.

BACKGROUND: Informing residents in long term care facilities (LTCFs) about their prognosis can help them prepare for the end of life. This study aimed to examine which proportion of European LTCF residents, close to death, are accurately prognosticated and consequently informed about their prognosis; and to examine factors related to accurate prognostication and discussion of prognosis. METHODS: A subsample of SHELTER study data was used, consisting of: 500 residents from 5 European countries, who died within 6 months after their last assessment, and had a valid answer on the item 'End stage disease, 6 or fewer months to live'. This item was used to indicate whether an accurate prognosis was established and discussed with residents. Generalized estimating equations were used to examine factors related to establishment and discussion of accurate prognosis. RESULTS: 86.4% of residents close to death did not receive an accurate prognosis. Residents with cancer; fatigue; dehydration; and normal mode of nutritional intake were more likely to have an accurate prognosis established and discussed. Accurate prognostication and prognosis discussion was less likely for residents who: had a diagnosis under 'other'; initiated interactions; and residents from Germany, Italy and the Netherlands. CONCLUSIONS: The great majority of residents close to death did not receive an accurate prognosis. Prognostication tools might help clinicians to increase their prognostic accuracy and communication training might help to discuss prognosis with residents.

Vital exhaustion and sudden cardiac death in the Atherosclerosis Risk in Communities Study.

OBJECTIVE: Vital exhaustion (VE), a construct defined as lack of energy, increased fatigue and irritability, and feelings of demoralisation, has been associated with cardiovascular events. We sought to examine the relation between VE and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: The ARIC Study is a predominately biracial cohort of men and women, aged 45-64 at baseline, initiated in 1987 through random sampling in four US communities. VE was measured using the Maastricht questionnaire between 1990 and 1992 among 13 923 individuals. Cox proportional hazards models were used to examine the hazard of out-of-hospital SCD across tertiles of VE scores. RESULTS: Through 2012, 457 SCD cases, defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual, were identified in ARIC by physician record review. Adjusting for age, sex and race/centre, participants in the highest VE tertile had an increased risk of SCD (HR 1.48, 95% CI 1.17 to 1.87), but these findings did not remain significant after adjustment for established cardiovascular disease risk factors (HR 0.94, 95% CI 0.73 to 1.20). CONCLUSIONS: Among participants of the ARIC study, VE was not associated with an increased risk for SCD after adjustment for cardiovascular risk factors.

Age and rest-activity rhythm as predictors of survival in patients with newly diagnosed lung cancer.

Disruption of the rest-activity rhythm in patients with lung cancer can accelerate cancer progression and affect survival. Rest-activity rhythm changes with age. Therefore, we investigated the effects of rest-activity rhythm and age on patients' survival. A total of 84 patients with lung cancer were recruited, then separated into two groups; younger patients aged under 65 years or elderly patients aged 65 and over. The dichotomy index (I < O) was used to estimate the rest-activity rhythm measured through the actigraphy motion detector. Cox proportional hazards models were adopted to investigate the effects of different variables on the patients' survival. After adjusting for confounding, the risk of earlier mortality in the younger patients with disrupted I < O were 2.52 (95%CI = 1.09-5.82) times higher than that in the younger patients with robust I < O (p = 0.03), the risk of earlier mortality in the elderly patients with disrupted I < O was 4.08 (95%CI = 1.91-8.68) times higher than that in the elderly patients with robust I < O (p < 0.001). Therefore, age and I < O influence the survival period of patients with lung cancer. Moreover, disrupted I < O has a substantial influence on elderly patients. In conclusion, aging and disrupted rest-activity rhythm negatively and jointly influenced the survival period of the patients with lung cancer and significantly increased their death risk.

The clinical epidemiology of fatigue in newly diagnosed heart failure.

BACKGROUND: Fatigue is a common and distressing but poorly understood symptom among patients with heart failure (HF). This study sought to evaluate the prevalence, predictors, and prognostic value of clinically documented fatigue in newly diagnosed HF patients from the community. METHODS: This retrospective cohort study consisted of 12,285 newly diagnosed HF patients receiving health care services through the Geisinger Health System, with passive data collection through electronic medical records (EMR). Incident HF, fatigue, and other study variables were derived from coded data within EMRs. A collection of 87 candidate predictors were evaluated to ascertain the strongest independent predictors of fatigue using logistic regression. Patients were followed for all-cause mortality for an average of 4.8 years. The associations between fatigue and 6-month, 12-month, and overall mortality were evaluated via Cox proportional hazards regression models. RESULTS: Clinically documented fatigue was found in 4827 (39%) newly diagnosed HF patients. Depression demonstrated the strongest association with fatigue. Fatigue was often part of a symptom cluster, as other HF symptoms including dyspnea, chest pain, edema, syncope, and palpitations were significant predictors of fatigue. Volume depletion, lower body mass index, and abnormal weight loss were also strong predictors of fatigue. Fatigue was not significantly associated with either 6-month (HR = 1.12, p = 0.16) or overall mortality (HR = 1.00, p = 0.89) in adjusted models. CONCLUSIONS: Fatigue is a commonly documented symptom among newly diagnosed HF patients, and its origins may lie in both psychologic and physiologic factors. Though fatigue did provide a prognostic signal in the short-term, this was largely explained by physiologic confounders. Proper therapeutic remediation of fatigue in HF relies on identifying underlying factors.

Fatigue is associated with excess mortality in the general population: results from the EPIC-Norfolk study.

BACKGROUND: Significant fatigue is a frequent reason for seeking medical advice in the general population. Patients, however, commonly feel their complaint is ignored. This situation may be because clinicians perceive fatigue to be benign, unrelated to traditional biomedical outcomes such as premature mortality. The present study aimed to investigate whether an association between significant fatigue and mortality actually exists, and, if so, to identify potential mechanisms of this association. METHODS: A population-based cohort of 18,101 men and women aged 40-79 years who completed a measure of fatigue (Short Form 36 vitality domain, SF36-VT) in addition to providing information on possible confounding factors (age, sex, body mass index, marital status, smoking, education level, alcohol consumption, social class, depression, bodily pain, diabetes, use of ß blockers, physical activity and diet) and mechanisms (haemoglobin, C-reactive protein and thyroid function) were followed up prospectively for up to 20 years. Mortality from all causes, cancer and cardiovascular disease was ascertained using death certification linkage with the UK Office of National Statistics. RESULTS: During 300,322 person years of follow-up (mean 16.6 years), 4397 deaths occurred. After adjusting for confounders, the hazard ratio (HR) for all-cause mortality was 1.40 (95 % confidence interval [CI] 1.25-1.56) for those reporting the highest fatigue (bottom SF36-VT quartile) compared with those reporting the lowest fatigue (top SF36-VT quartile). This significant association was specifically observed for those deaths related to cardiovascular disease (HR 1.45, 95 % CI 1.18-1.78) but not cancer (HR 1.09, 95 % CI 0.90-1.32). Of the considered mechanisms, thyroid function was most notable for attenuating this association. The risk of all-cause mortality, however, remained significant even after considering all putative confounders and mechanisms (HR 1.26, 95 % CI 1.10-1.45). CONCLUSIONS: High levels of fatigue are associated with excess mortality in the general population. This commonly dismissed symptom demands greater evaluation and should not automatically be considered benign.

Comparison of Frailty Phenotypes for Prediction of Mortality, Incident Falls, and Hip Fracture in Older Women.

OBJECTIVES: To compare the ability of the commonly used Women's Health Initiative (WHI) and Cardiovascular Health Study (CHS) frailty phenotypes to predict falls, hip fracture, and death in WHI Clinical Trial participants aged 65 and older. DESIGN: Longitudinal cohort study. SETTING: WHI Clinical Trial. PARTICIPANTS: Participants with data for WHI and CHS frailty phenotypes (N = 3,558). MEASUREMENTS: Frailty was operationally defined in the CHS as the presence of three or more of weight loss, poor energy, weakness, slowness, and low physical activity. WHI operationalized frailty similarly but with the RAND-36 physical function scale substituted for slowness and weakness (RAND-36 physical function scale score <13 = 2 points, 13-78 = 1 point, >78 = 0 points). Frailty was defined as a summary score of 3 or greater, prefrailty as a score of 2 or 1, and nonfrailty as a score of 0. Outcomes were modeled using Cox regression. Harrell C-statistics were compared for models containing alternative instruments. RESULTS: Approximately 5% of participants were frail based on the CHS or WHI phenotype. The WHI frailty phenotype was associated with higher rates of falls (hazard ratio (HR) = 1.48, P = .003), hip fracture (HR = 1.87, P = .04), and death (HR = 2.32, P < .001). Comparable HRs in CHS-phenotype frail women were 1.32 (P = .04), 1.08 (P = .83), and 1.91 (P < .001), respectively. Harrell C-statistics revealed marked but insignificant differences in predicting abilities between CHS and WHI phenotype models (P > .50 for all). CONCLUSION: The WHI phenotype, which does not require direct measurements of physical performance, might offer a practical advantage for epidemiological and clinical needs.

Prevalence of Sudden Death in Palliative Care: Data From the Australian Palliative Care Outcomes Collaboration.

CONTEXT: Advanced, life-limiting illnesses are likely to have a predictable functional decline through a terminal phase to death, but some patients may also die suddenly. To date, empirical evidence characterizing "sudden death" in hospice/palliative care is lacking. OBJECTIVES: The aim of this study was to determine prevalence and clinicodemographic predictors of sudden death in hospice/palliative care. METHODS: This is a longitudinal consecutive cohort study of prospectively collected national data in 104 specialist palliative care services from the Australian Palliative Care Outcomes Collaboration. Patients who died between July 1, 2013, and June 30, 2014, with one or more measurement of Australian-modified Karnofsky Performance Status (AKPS) in the last 30 days of life were included. "Sudden death" was defined as a lowest AKPS score of 50 or more in the last seven days of life and excluded anyone with "terminal phase" as their last phase before death. Predictors were defined using logistic regression. RESULTS: In total, 13,966 patients were included, mean age 73.6 (SD 13.6) years, 46% women, and 77% had cancer. During the seven days before death, there were 20,992 AKPS measurements; median 1 (interquartile range 1-2) per patient. Four percent of deaths (one of 25) were sudden, predicted independently by having lung cancer (odds ratio [OR] 2.64), cardiovascular disease (OR 1.94), other cancers (OR 1.63), being male (OR 1.23), younger, worse fatigue, and worse breathlessness. Sudden death was associated with higher rates of death at home (OR 3.2; 95% CI 2.9 to 3.6). CONCLUSION: This study quantifies rates of sudden death in hospice/palliative care and has implications for conversations about prognosis between clinicians, patients, and their families.

Traffic accidents involving fatigue driving and their extent of casualties.

The rapid progress of motorization has increased the number of traffic-related casualties. Although fatigue driving is a major cause of traffic accidents, the public remains not rather aware of its potential harmfulness. Fatigue driving has been termed as a "silent killer." Thus, a thorough study of traffic accidents and the risk factors associated with fatigue-related casualties is of utmost importance. In this study, we analyze traffic accident data for the period 2006-2010 in Guangdong Province, China. The study data were extracted from the traffic accident database of China's Public Security Department. A logistic regression model is used to assess the effect of driver characteristics, type of vehicles, road conditions, and environmental factors on fatigue-related traffic accident occurrence and severity. On the one hand, male drivers, trucks, driving during midnight to dawn, and morning rush hours are identified as risk factors of fatigue-related crashes but do not necessarily result in severe casualties. Driving at night without street-lights contributes to fatigue-related crashes and severe casualties. On the other hand, while factors such as less experienced drivers, unsafe vehicle status, slippery roads, driving at night with street-lights, and weekends do not have significant effect on fatigue-related crashes, yet accidents associated with these factors are likely to have severe casualties. The empirical results of the present study have important policy implications on the reduction of fatigue-related crashes as well as their severity.

[Sleepiness and accidental risk]. / Somnolence et risque accidentel.

Sleepiness while driving is both a very common phenomena regarding 10 to 15% of drivers and one of the main causes of death on highways (one third of fatal accidents). Sleepiness results mainly from behavioural causes: sleep deficit or irregular work schedules. However, many sleep diseases and hypnotics may also induce sleepiness at the wheel. Several objective and subjective measures have been validated to assess sleepiness. Road safety and information to the drivers have now to focus on better informing drivers on the rules of preventing sleepiness at the wheel in order to avoiding hundred of accidents in the next future.

Karoshi Related to Labor Intensity and Risk of Cardiovascular Events: A Case Report.

Karoshi remains one of the most troublesome issues in forensic identification. It is rather a social medicine than a clinical disease. Japanese scholars pioneered examining the relation between sud- den cardiac death (SCD) and chronic fatigue from long time and/or high-tension work. In the current case, a 55-year-old man, whose job was loading and carrying heavy cement bags, was found dead after 11 days of continuous hard work. His family members sued the cement factory for his death and claimed for compensation. The problem was the difficulty of identifying the causative relation without the precedent or the relevant regulations. However, the forensic problems were finally acknowledged after autopsy and calculation of labor intensity. The lawsuit was won as the first case pertaining to Karoshi in the Chinese court.

Experiência de vigilância no setor canavieiro: desafios para interromper a "maratona" perigosa dos canaviais / Surveillance experience in the sugarcane sector: challenges in disrupting the perilous "marathon" of the sugarcane plantations

O setor sucroalcooleiro cresce anualmente com participação expressiva do estado de São Paulo que concentra atualmente cerca de 42,9 % das usinas do país. A cadeia produtiva é objeto de preocupação de órgãos públicos e da sociedade civil por expor trabalhadores migrantes a riscos decorrentes do processo de trabalho. Em São Paulo, de 2006-2009, a Vigilância em Saúde do Trabalhador construiu duas iniciativas para enfrentar problemas relacionados às condições de trabalho e moradia de trabalhadores da cana. O objetivo do artigo apresentado na modalidade de ensaio é analisar as experiências em seu contexto. O método usado associa análise documental à percepção dos autores que participaram das ações. As experiências possibilitaram melhorias nessas condições e início de debate público sobre as condições do trabalho exaustivo. As intervenções resultaram na definição de normas sanitárias e iniciativas no nível legislativo e judiciário, mas mesmo aquelas mais exitosas não conseguiram alcançar os determinantes organizacionais, especialmente a remuneração por produção, que desafia a ação tradicional de vigilância e tem seus impactos agravados pela fragilidade da representação dos trabalhadores.

The sugar-alcohol sector is growing year by year, especially in the state of Sao Paulo where approximately 42.9% of the sugar-ethanol plants are concentrated. The production chain is a subject for concern to public agencies and to civil society by exposing migrant workers to risks arising from the work process. In Sao Paulo, from 2006-2009, Occupational Health Surveillance (VISAT) set up two initiatives to address problems related to the housing and working conditions of sugarcane workers. The objective of this article presented in the form of an essay is to analyze the experiences in their context. The methodology used combines document analysis with the perception of the authors who participated in the actions. The experience led to improvements in these conditions and fostered public debate on the conditions of such physically demanding work. The interventions resulted in a definition of sanitary norms and initiatives at the legislative and judicial level, but even the most successful measures failed to attain the organizational targets, especially a production remuneration structure that challenges the traditional action of surveillance and the impacts were weakened due to the fragility of worker representation for the sector.

[Surveillance experience in the sugarcane sector: challenges in disrupting the perilous "marathon" of the sugarcane plantations]. / Experiência de vigilância no setor canavieiro: desafios para interromper a "maratona" perigosa dos canaviais.

The sugar-alcohol sector is growing year by year, especially in the state of Sao Paulo where approximately 42.9% of the sugar-ethanol plants are concentrated. The production chain is a subject for concern to public agencies and to civil society by exposing migrant workers to risks arising from the work process. In Sao Paulo, from 2006-2009, Occupational Health Surveillance (VISAT) set up two initiatives to address problems related to the housing and working conditions of sugarcane workers. The objective of this article presented in the form of an essay is to analyze the experiences in their context. The methodology used combines document analysis with the perception of the authors who participated in the actions. The experience led to improvements in these conditions and fostered public debate on the conditions of such physically demanding work. The interventions resulted in a definition of sanitary norms and initiatives at the legislative and judicial level, but even the most successful measures failed to attain the organizational targets, especially a production remuneration structure that challenges the traditional action of surveillance and the impacts were weakened due to the fragility of worker representation for the sector.

Quality of life, fatigue and local response of patients with unstable spinal bone metastases under radiation therapy--a prospective trial.

BACKGROUND: To evaluate the local response according to stability after radiotherapy (RT) with a special focus on quality-of-life (QoL), fatigue, pain and emotional distress in patients with unstable spinal bone metastases. METHODS: In this prospective trial, 30 patients were treated from September 2011 until March 2013. The stability of osteolytic metastases in the thoracic and lumbar spine was evaluated on the basis of the Taneichi-score after three and six months. EORTC QLQ-BM22, EORTC QLQ-FA13, and QSC-R10 were assessed at baseline, and three months after RT. RESULTS: After 3 months, 25% (n = 6) and after 6 months 33.3% (n = 8) were classified as stable. QoL, fatigue, and emotional distress showed no difference over the course. The pain response 3 months after RT showed a significant difference (p < 0.001). Pathological fractures occurred in 8.3% of the patients (n = 2) within six months following RT. CONCLUSIONS: Our trial demonstrated that RT can improve stability in one third of patients over a 6-months period with unstable spinal metastases. Importantly, for these patients pain relief was detected but RT had no impact on QoL, fatigue, and emotional distress. TRIAL REGISTRATION: Clinical trial identifier NCT01409720.