Cancer cachexia - Adopting a systems wide approach

Cancer cachexia results in the death of approximately 2 million people worldwide annually. Despite the impact of this devastating condition, there is limited therapy and no standard of care. Although multiple definitions exist, confusion remains as a true understanding of the biology has not yet been achieved and distinct phases of cachexia have not been examined. Research has mainly focused on weight loss and muscle wasting, but cachexia is increasingly recognized as a multiorgan disorder involving adipose tissue, liver, brain, gut and heart, with systemic inflammation a central unifying feature

Longitudinal characterisation of cachexia in patients undergoing surgical resection for cancer

PURPOSE OF REVIEW: The complexity of the cancer cachexia phenotype has undoubtedly hindered researchers' understanding of this devastating syndrome. The presence and magnitude of host-tumour interactions are rarely considered during clinical decision-making within the current staging paradigm. Furthermore, treatment options for those patients who are identified as suffering from cancer cachexia remain extremely limited.RECENT FINDINGS: Previous attempts to characterise cachexia have largely focussed on individual surrogate disease markers, often studied across a limited timeframe. While the adverse prognostic value of clinical and biochemical features is evident, the relationships between these are less clear. Investigation of patients with earlier-stage disease could allow researchers to identify markers of cachexia that precede the refractory stage of the wasting process. Appreciation of the cachectic phenotype within 'curative' populations may aid our understanding of the syndrome's genesis and provide potential routes for prevention, rather than treatment.SUMMARY: Holistic, longitudinal characterisation of cancer cachexia, across all at-risk and affected populations, is of vital importance for future research in the field. This paper presents the protocol for an observational study aiming to create a robust and holistic characterisation of surgical patients with, or at risk of, cancer cachexia.</p

The relationship between imaging-based body composition analysis and the systemic inflammatory response in patients with cancer: a systematic review

Background and aim: Cancer is the second leading cause of death globally. Nutritional status (cachexia) and systemic inflammation play a significant role in predicting cancer outcome. The aim of the present review was to examine the relationship between imaging-based body composition and systemic inflammation in patients with cancer. Methods: MEDLINE, EMBASE, Cochrane Library and Google Scholar were searched up to 31 March 2019 for published articles using MESH terms cancer, body composition, systemic inflammation, Dual energy X-ray absorptiometry (DEXA), magnetic resonance imaging (MRI), ultrasound sonography (USS) and computed tomography (CT). Studies performed in adult patients with cancer describing the relationship between imaging-based body composition and measures of the systemic inflammatory response were included in this review. Results: The literature search retrieved 807 studies and 23 met the final eligibility criteria and consisted of prospective and retrospective cohort studies comprising 11,474 patients. CT was the most common imaging modality used (20 studies) and primary operable (16 studies) and colorectal cancer (10 studies) were the most commonly studied cancers. Low skeletal muscle index (SMI) and systemic inflammation were consistently associated; both had a prognostic value and this relationship between low SMI and systemic inflammation was confirmed in four longitudinal studies. There was also evidence that skeletal muscle density (SMD) and systemic inflammation were associated (9 studies). Discussion: The majority of studies examining the relationship between CT based body composition and systemic inflammation were in primary operable diseases and in patients with colorectal cancer. These studies showed that there was a consistent association between low skeletal muscle mass and the presence of a systemic inflammatory response. These findings have important implications for the definition of cancer cachexia and its treatment

Pain in malignant pleural mesothelioma: a prospective characterisation study.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is associated with severe pain. The underlying neurobiology of this is complex. The primary aim of this study was to characterize pain in MPM. METHODS: This study was undertaken as part of a trial examining radiotherapy for the treatment of pain in MPM (ISRCTN 10644347). Patients had MPM with associated pain for which radiotherapy was planned and a worst pain score ≥ 4/10. The following assessments were undertaken: clinical neuropathic pain assessment, Brief Pain Inventory (BPI), Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), Short form of the McGill Pain Questionnaire (SF-MPQ), and Quantitative Sensory Testing (QST). The relationship of these characteristics and response to radiotherapy was assessed. Unless stated, medians and interquartile range (IQR) are used. RESULTS: Thirty-seven patients were recruited. Average pain and worst pain was 4 (4-6) and 8 (6-8), respectively. Higher average pain and higher worst pain scores were associated with higher interference scores on the BPI, P &lt; 0.001 and P &lt; 0.0005. Twenty patients (54%) had a clinical diagnosis of neuropathic pain, and of these, only six patients (40%) screened positively for neuropathic pain using the LANSS. Patients with a high LANSS also had higher BPI and SF-MPQs. The presence of neuropathic pain (clinically or by LANSS) did not predict response to radiotherapy, P &lt; 0.05. The SF-MPQ scores were higher in those with abnormal cool sensation on QST (P = 0.016). CONCLUSION: Pain in mesothelioma varies among patients and may have neuropathic components. An adequate pain assessment is necessary to guide the clinician in the appropriate choice of analgesics

Non-steroidal anti-inflammatory drugs (NSAIDs) in cancer pain:A database analysis to determine recruitment feasibility for a clinical trial

BACKGROUND: Insufficient evidence exists to support or refute use of NSAIDs for managing cancer pain. Palliative physicians support a placebo-controlled trial of NSAIDs as strong opioid adjuncts for cancer-induced bone pain as the most pragmatic design to benefit clinical practice. AIM: We aimed to determine patient numbers receiving palliative radiotherapy for cancer-induced bone pain, estimate the suitability of NSAID prescription and determine survival, guiding future trial feasibility. DESIGN: A retrospective observational database analysis was undertaken using 5 years of routinely collected regional radiotherapy and healthcare data, filtered to achieve a cohort with cancer-induced bone pain. Demographics and survival were linked to available serology and co-morbidity data. SETTING/PARTICIPANTS: Data was sourced from the regional Leeds Cancer Centre, a tertiary care setting. Patients who underwent palliative single fraction 8 gray (Gy) radiotherapy treatment for cancer-induced bone pain were included, totalling 2411 over 5 years. RESULTS: A mean of 478 patients received palliative radiotherapy for cancer-induced bone pain annually. Median age (IQR) was 70 (62–77); negatively skewed (−0.69). 65.3% died within 1 year of radiotherapy; 48.0% within 6 months. Age was not associated with survival on univariable analysis (HR 0.999 (95% CI 0.996–1.003)). Serology from 1063 patients (44.2%) were available; eGFR was ⩾60 mL/min/1.73 m(2) in 83.0%. From available data (1352 pts; 51.6% of sample), 20.2% had a coded co-morbidity contra-indicating NSAIDs. Combining serology and co-morbidities, 68.5% could be considered for NSAID prescription. CONCLUSIONS: Patient numbers at a regional radiotherapy centre support the feasibility of trial recruitment. Available serology and co-morbidity data suggest two-thirds may be suitable for NSAID prescription

A comparison of CT-body composition measurements in non-cancer and cancer patients from a single UK centre

Objectives: Establish the prevalence of low skeletal muscle index and density in our population, by comparing age and sex matched cohorts of patients with and without cancer, using standardized methodology for CT-Body composition (CT-BC). Methods: A retrospective analysis of prospectively collected data. Patients admitted to our institution between 17th March 2020 - 1st May 2020, with confirmed coronavirus disease and imaging suitable for CT-BC (n=52), were age and sex matched with patients undergoing resection for colorectal cancer (n=52). Results: 104 patients were included in the final analysis. 43% (n=45) were male, 77% (n=80) were aged 65 years or older, 50% (n=50) were overweight (BMI ≥25) and 53% (n=55) were systemically inflamed (mGPS ≥1). The prevalence of a low SMI (56% vs. 65%) and low SMD (83% vs. 67%) was similar between cohorts. A low SMI and SMD were both associated with age (p&lt;0.05 and p&lt;0.01, respectively) on univariate analysis. On multivariate analysis, a low SMD was independently associated with age (OR 2.38 (1.34-4.22), p=0.003) and mGPS (OR 2.10 (1.20-3.68), p=0.01). Conclusions: In conclusion, the prevalence of a low SMI and low SMD was similar in non-cancer and cancer cohorts in our institution

Defining non-inferiority margins in randomised controlled surgical trials: a protocol for a systematic review

Background: The reporting of randomised controlled non-inferiority (NI) drug trials is poor with less than 50% of published trials reporting a justification of the NI margin. This is despite the introduction of the Consolidated Standards of Reporting Trials (CONSORT) extension on reporting of NI and equivalence in randomised trials. It is critical to set the appropriate NI margin as this choice dictates the conclusions of the trial. Methods to estimate the margin are heterogeneous but generally based on clinical judgement and statistical reasoning, and hence tailored to each clinical situation. Yet an appraisal of NI in clinical trials has not been undertaken. Therefore the aim of this systematic review is to assess the reporting and methodological quality of defining the NI margin. Surgical NI trials have been chosen as our prototype to assess this. Methods: We will conduct a systematic review of published randomised controlled trials in abdominal surgery that use an NI design. Key eligibility criteria will be: surgical intervention in at least one trial arm; adult patients and a sample size of 100 or more. Ovid MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials will be searched from inception until the date of the search. Identified studies will be assessed for reporting according to the CONSORT recommendations. The outcomes are the description of the methods for defining the NI margin, and the robustness of the NI margin estimation. The latter will be based on simulations using alternative assumptions for model parameters. The results of the simulation will be compared with the trial authors’ conclusions. Anticipated results: The review will describe and appraise the design and reporting of surgical NI trials including shortcomings thereof and allow a comparison with pharmaceutical trials. These findings will inform researchers on the appropriate design and pitfalls when conducting surgical randomised controlled trials with an NI design and promote thorough and standardised reporting of study findings. Ethics and dissemination: Ethical approval is not required and any changes to the protocol will be communicated via the registration platform. The final manuscript will be submitted to a journal for publication and the findings will be disseminated through conference presentations to inform researchers and the public