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

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

Oral ketamine vs placebo in patients with cancer-related neuropathic pain

Ketamine hydrochloride is used as an adjuvant treatment for cancer-related neuropathic pain, but evidence of its effectiveness is limited.1 Findings of a large trial investigating the use of ketamine for general cancer pain were negative, but the population studied did not specifically have neuropathic pain. A randomized trial of oral ketamine for cancer-related neuropathic pain has been called for, and the present trial addresses that need

Inflammation and performance status:the cornerstones of prognosis in advanced cancer

Context: In advanced cancer, although performance status (PS), systemic inflammatory response and nutritional status are known to have prognostic value, geographical variations and sociodemographic indexes may also impact survival. Objectives: This study compares validated prognostic factors in two international cohorts and establishes a prognostic framework for treatment. Methods: Two international biobanks of patients (n=1.518) with advanced cancer were analyzed. Prognostic factors (Eastern Cooperative Oncology Group Performance Status [ECOG-PS], body mass index [BMI] and modified Glasgow Prognostic Score [mGPS]) were assessed. The relationship between these and survival was examined using Kaplan–Meier and Cox regression methods. Results: According to multivariate analysis, in the European cohort the most highly predictive factors were BMI &lt;20 kg/m2 (hazard ratio [HR] 1.644), BMI 20-21.9 kg/m2 (HR 1.347), ECOG-PS (HR 1.597–11.992) and mGPS (HR 1.843–2.365). In the Brazilian cohort, the most highly predictive factors were ECOG-PS (HR 1.678–8.938) and mGPS (HR 2.103–2.837). Considering gastrointestinal cancers in particular (n=551), the survival rate at 3 months in both cohorts together ranged from 93% (mGPS 0, PS 0–1) to 0% (mGPS 2, PS 4), and from 81% (mGPS 0, BMI &gt;28 kg/m2) to 44% (mGPS 2, BMI &lt;20 kg/m2). Conclusion: The established prognostic factors that were compared had similar prognostic capacity in both cohorts. A high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer survival of patients with advanced cancer in the prospective European and Brazilian cohorts

Are CT-derived muscle measurements prognostic, independent of systemic inflammation in good performance status patients with advanced cancer?

The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1–68.1). On univariate analysis, cancer type (p &lt; 0.05) and mGPS (p &lt; 0.001) were significantly associated with OS. On multivariate analysis, only mGPS (p &lt; 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS (p &lt; 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer

Lactate dehydrogenase: Relationship with the diagnostic GLIM criterion for cachexia in patients with advanced cancer

Background: Although suggestive of dysregulated metabolism, the relationship between serum LDH level, phenotypic/aetiologic diagnostic Global Leadership Initiative on Malnutrition (GLIM) criteria and survival in patients with advanced cancer has yet to examined. Methods: Prospectively collected data from patients with advanced cancer, undergoing anti-cancer therapy with palliative intent, across nine sites in the UK and Ireland between 2011–2016, was retrospectively analysed. LDH values were grouped as &lt;250/250–500/&gt;500 Units/L. Relationships were examined using χ2 test for linear-by-linear association and binary logistics regression analysis. Results: A total of 436 patients met the inclusion criteria. 46% (n = 200) were male and 59% (n = 259) were ≥65 years of age. The median serum LDH was 394 Units/L and 33.5% (n = 146) had an LDH &gt; 500 Units/L. LDH was significantly associated with ECOG-PS (p &lt; 0.001), NLR (p &lt; 0.05), mGPS (p &lt; 0.05) and 3-month survival (p &lt; 0.001). LDH was significantly associated with 3-month survival independent of weight loss (p &lt; 0.01), BMI (p &lt; 0.05), skeletal muscle mass (p &lt; 0.01), metastatic disease (p &lt; 0.05), NLR (p &lt; 0.05) and mGPS (p &lt; 0.01). Discussion: LDH was associated with performance status, systemic inflammation and survival in patients with advanced cancer. LDH measurement may be considered as an aetiologic criteria and become a potential therapeutic target in the treatment of cancer cachexia

Is radiotherapy useful for treating pain in mesothelioma?:A phase II trial

IntroductionRadiotherapy is often used to treat pain in malignant pleural mesothelioma (MPM), although there is limited evidence to support this. The aim of this trial was to assess the role of radiotherapy for the treatment of pain in MPM.MethodsA multicentre, single arm phase II trial was conducted. Eligible patients fulfilled the following criteria: pathological or radiological diagnosis of MPM; pain secondary to MPM; radiotherapy indicated for pain control; and more than 18 years of age. Patients had assessments of pain and other symptoms at baseline and then received 20 Gy in five daily fractions. Key follow-up points were 5 and 12 weeks posttreatment. The primary end point measure was assessment of pain at the site of radiotherapy at 5 weeks. Secondary end points included effects on quality of life, breathlessness, fatigue, mood, toxicity, and the radiological response.ResultsForty patients were recruited from three UK oncology centers. Fourteen patients had a clinically meaningful improvement in their pain 5 weeks post radiotherapy (intention to treat), with five patients having a complete improvement. On the basis of a complete case analysis of the 30 patients assessable at week 5, 47% (confidence intervals, 28.3–65.7) of patients alive at week 5 had an improvement in their pain. There was no improvement in other key symptoms or quality of life.ConclusionsRadiotherapy for pain control in MPM is an effective treatment in a proportion of patients. Future studies examining differing radiotherapy regimens with a view to improving response rates are warranted