Navigating Cancer Cachexia : Innovations in Understanding and Treatment. Journey through the latest breakthroughs in cancer research. From the role of sarcopenia in hepatocellular carcinoma to the nutritional challenges in nasopharyngeal carcinoma, explore how these insights shape patient care and treatment strategies.
There is an urgent need to find predictive biomarkers for the prognosis of non-small cell lung cancer for survival assessment. Tumour-related factors, such as the pathological stage or histological subtype, are used widely but often vary in patient outcome. Hence, haematological inflammatory parameters, such as neutrophils, lymphocytes and platelets have been used to reflect the inflammation found in cancer. These biomarkers demonstrate prognostic value in cancers such as non-small cell lung cancer. However, it remains unclear which specific combination of biomarkers may help in assessing prognosis, so this study used the newly developed inflammatory burden index (IBI). It was found to be associated with survival, 90-day outcomes, length of hospitalisation and cachexia in non-small cell lung cancer patients. Hence, this may be an advantageous tool for prognosis prediction.
This review by Xie H et al. aimed to compare the prognostic value of inflammation biomarkers in patients with non-small cell lung cancer.
Many types of conditions and diseases are associated with wasting syndromes such as cachexia. However, despite its prevalence, there is limited knowledge regarding the diagnosis and treatment of cachexia due to our lack of understanding of the causative molecular mechanisms. Cachexia must be viewed through an immunological context to understand its full consequences on patient prognosis. For example, it is known that cytokines such as tumour necrosis factor, IL-1β, IL-6 and IFNγ are consistently upregulated in cases of cachexia in both immune and non-immune cells. This appears to lead to the changes in transcriptional regulation, inducing catabolic pathways in muscles and adipose tissue. Yet, despite this understanding, targeting such cytokines has not shown successful in clinical settings. Further research has also been done to identify the involvement of immune cells such as macrophages, neutrophils, myeloid-derived suppressor cells and T cells in cachexia. Yet, their full involvement in the condition is not yet understood. Hence, many questions remain about this interplay between cachexia and immune system. It is vital to discover the common and unique properties of cancer cachexia and infection-associated cachexia to develop effective therapeutic strategies for cachexia.
This review by Baazim H et al. aimed to highlight the relationship between the immune system and cachexia, as well as our current lack of knowledge surrounding this syndrome.
The guidelines most commonly used to diagnose cachexia are the European Palliative Care Research Collaborative (EPCRC) guidelines. Here, cachexia is classified according to weight loss. However, for patients in palliative care with advanced cancer, there are often cases of oedema and ascites. This hampers the ability to detect weight loss, affecting the likelihood to be diagnosed with cachexia. Therefore, this study wished to examine the validity of diagnosing cachexia based upon other items. Alongside weight loss, this includes factors such as fatigue, decreasing muscle mass in the mid-upper arm, abnormal levels of white blood cells, reduced food intake and others. This study validated the CSS, Cachexia Staging Score, which demonstrated that patients without cachexia had a higher survival rate, and that the risk of mortality was higher with more severe cachexia. They also validated that cachexia prevalence was not significantly different compared to previous studies. Hence, such a multidimensional assessment helps to evaluate disorders including cachexia.
This review by Ueshima J et al. aimed to validate the Cachexia Staging Score for patients with advanced cancer who are under palliative care.
Exosomes are extracellular vesicles that contain cargo such as proteins, lipids, nucleic acids and more. Their function is to alter cell signalling in the cell it releases its cargo into. For example, exosomes have been seen to alter muscle and adipose tissue metabolism. This has led to the thought that they may be involved in cancer cachexia. Inhibiting tumour derived exosome release therefore may improve survival and cancer cachexia in patients. Specifically, tumour derived exosome micro-RNAs have been associated with muscle wasting and tumour presence. Furthermore, they may package inflammatory cytokines. This could play a causal role in cancer cachexia as increase cytokine circulation is thought to precede the loss of appetite in cachexia, holding a causal role in the disease progression.
This review by Pitzer CR et al. aimed to summarise the potential involvement of tumour derived exosomes in cancer cachexia.
Currently, there are many interventions and treatments for cancer cachexia. Early nutritional intervention and care are essential to ensure that sufficient nutritional requirements are met for the patients. This includes oral nutrition where possible, as well as nutrition and exercise therapy. Furthermore, preventive care to minimise loss of skeletal muscle mass is vital. Pharmacological options are also available. These include many options, such as non-steroidal anti-inflammatory drugs, anti-cytokine therapy and eicosapentaenoic acid. Furthermore, steroids are often used for cachexia. However, they have limited effects are limited, so recently, anamorelin hydrochloride, a ligand with a similar action to that of ghrelin, was developed. It is used to treat weight loss by increasing appetite and has been approved for use in cachexia. Anamorelin hydrochloride holds great promise to function as an effective therapeutic drug for cancer cachexia.
This review by Watanabe H & Oshima T aimed to review the current treatments of cancer cachexia, as well as anamorelin hydrochloride, a new and promising treatment.
Personalised therapy is a challenge in advanced colorectal cancer care. Much research has been carried out on prognostic and predictive markers of this disease, and a strong correlation was found between sarcopenia and survival in such patients. Currently, selecting personalised strategies for patients is based on very few parameters, not making sufficient use of all available clinical information. Therefore, this paper suggests that it is possible to use body composition and liver tumour burden through automated extraction from CT images. Such automated segmentation would allow one to extract prognostic parameters from the routine imaging data which is collected from patients. This could provide personalised survival modelling for colorectal cancer patients. Specifically, the inclusion of body composition as a factor holds great promise in improving current strategy making for patient care.
This review by Keyl J et al. aimed to explore automated assessment of body composition and liver metastases from CT images can improve personalised risk assessment.
In this study, TOV21G cancer cachexia mouse models were used to demonstrate impaired muscle function and performance which is seen in cachexia patients. With growth differentiation factor 15, GDF15, neutralization, the mice were seen to exhibit restored muscle function and performance. GDF15 is a stress-responsive cytokine which is secreted by many cells, including tumour cells and damaged cells. GDF15 functions by activating glial cell line-derived neurotrophic factor, GDNF, receptor GFRAL. This is expressed in the hindbrain and leads to reducing food intake and weight loss. This is relevant to cachexia patients, and patients with chronic diseases such as heart failure, as their GDF15 levels are significantly higher than that of healthy people. In this study, the mice were treated with mAB2, an anti-GDF15 antibody. They demonstrated weight gain in terms of fat mass and lean mass, improved muscle function and physical performance. Hence, it is thought that GDF15-related therapy may be effective for patients with cachexia. However, symptoms of cachexia such as fatigue do not appear to be related to GDF15 levels, so further exploration is necessary.
This review by Kim-Muller JY et al. aimed to explore how GDF15 levels are related to weight loss and highlight how GDF15 neutralization could be an option for treating cachexia.
All types of ovarian cancers hold a high risk of morbidity and mortality for the patients. Currently, there are many efforts to assess ovarian cancer progression, to allow for the development of accurate treatment and management plans for preventing mortality in the long-term. A physical indicator of increased vulnerability is frailty. Frailty can lead to falls, hospitalisation and increased risk of death. Generally, frailty is closely associated with poor prognosis and shorter progression-free survival in many conditions, including ovarian cancer. However, diagnosing frailty is complex, due to a lack of a set definition and due to comorbidities appearing in older patients. Although this study draws useful conclusions, its limitation holds that some confounding factors could not be adjusted for, meaning further research is needed to understand the interplay between ovarian cancer and frailty.
This review by Can E et al. aimed to understand the prognostic value of frailty to predict complications and mortality in patients with ovarian cancer.
A consensus is held that all tumour patients should be offered the opportunity for regular screenings for nutritional disorders, and their results should be monitored. This is because after cancer treatments, there is a high risk of metabolic syndrome. Healthy diets and regular exercise can help with this. Nutritional disorders are a huge issue for cancer patients because almost half of all advanced tumour patients experience eating and weight loss issues - this increases the threat of cachexia. Food intake should be kept normal (not through enteral tube or parenteral feeding) for as much as possible, with good nutrition reducing the risk of tumour recurrence. In palliative cases, hunger and thirst should be subjectively satisfied to alleviate distress.
This review by Arends J aimed to assess the role of nutrition in cancer patients, all the way to palliative cases.
Currently, medical treatment for cancer is personalised by looking at genetic and molecular factors of cancer cells. However, for characterising patients, factors such as age, weight, BMI, comorbidities, etc are used. Hence, there is no set, universal variable(s) to be used in managing cancer. It is possible that this is the reason that many anticancer drugs perform poorly clinically, due to this variability between patients. One of the factors that can be used is chronological age, which defines the patient’s accumulated damage to their system. Age is an accurate predictor of various outcomes, including the outcomes of anticancer drug therapies. For example, patients between the ages of 65-69 are often less likely to respond well to chemotherapy. A way to index age is sarcopenia, but due to the complex, varying body compositions associated with tumour growth, it is difficult to use sarcopenia consistently as an index for age in cancer management.
This review by Laviano A aimed to explore variables, such as sarcopenia and ageing, in their effects on cancer and anticancer drug successes.
Out of all non-accidental deaths in the United States, paediatric cancer is the number one cause of death. Of children with cancer, 80% experience malnutrition during their treatment programmes. This statistic is dangerous, as malnutrition, as well as cachexia, worsen toxicity of treatment and the child’s quality of life. Yet, there are no standard definitions and nutritional interventions within clinical practice, with this varying between hospitals and clinicians on how to screen for and intervene with malnutrition. For example, some studies have explored Peptamen supplements for children with acute lymphoblastic leukaemia, whilst others tried isocaloric and hypercaloric supplements. Overall, there is a significant lack of nutrition-based studies in paediatric oncology patients. Yet, overall, it has been seen that nutritional interventions in general are seen to increase the patient’s weight and decrease the risk of complications during treatment. Furthermore, incorporating nutritional screening into the patient’s management decreases their risk for malnutrition.
This review by Franke J et al. aimed to explore the current available malnutrition screening and intervention methods across different hospitals and studies for childhood cancer, and to underscore the lack of a standard management system.
The Journal of Cachexia, Sarcopenia and Muscle mainly publishes research on cachexia, sarcopenia and muscle wasting disorders, but also includes papers on cancer, heart failure, ageing and many other conditions. Before November 2022, there were seen to be 775,000 downloads of the articles within the journal, with the top three countries downloading articles being China, the US and Japan. The most downloaded and cited article is entitled, Cachexia as a major underestimated and unmet medical need: facts and numbers.
This review by Frohlich A et al. aimed to review the successes of the Journal of Cachexia, Sarcopenia and Muscle in 2022.
Pancreatic ductal adenocarcinoma, PDAC, is one of the most fatal types of solid tumours. It is also linked to a high prevalence of cachexia, with around 80% of PDAC patients exhibiting cachexia. There is one hypothesis, the endocrine organ–like tumour hypothesis, which aims to explain the reasons behind cancer cachexia occurring during pancreatic ductal adenocarcinoma. Some of the reasons include metabolites, epigenetic changes, hormonal disturbance and genetic instability may be behind the development of cancer cachexia. Generally, the belief is held that metabolic disruption is the process behind cachexia development, but it is also believed there is not one single factor that triggers it.
This review by Yu Y et al aimed to synthesise an understanding of cancer cachexia development and the response of cachexia to current available treatments.
For patients with head and neck cancer, malnutrition and frailty are linked with adverse treatment outcomes, higher mortality rates, complications post-surgery and generally lower quality of life. However, the relationship between malnutrition and frailty is not fully known. It is, however, clear that these two conditions often coexist, suggesting they may share similar risk factors. In this study on 197 patients, it was found that the risk of malnutrition is strongly positively associated with frailty. However, some other interesting factors were discovered. Alcohol consumption was shown to present a greater risk of developing malnutrition, but on the other hand, alcohol consumption seems protective for being frail. Overall, these conditions often coexist but do not always fully overlap: screening for both conditions is therefore recommended.
This review by Dewansingh P et al aimed to understand the relationship between the risk of malnutrition and frailty in patients with head and neck cancer.
Cancer cachexia has no simple criteria to distinguish its severity in patients. Diagnostic criteria generally includes observing factors such as weight loss, fatigue, abnormal levels of albumin, reduced food intake and others. However, this study explored the cachexia staging score, a method of diagnosing cancer cachexia severity. This score explores strength, walking, rising from a chair, climbing up stairs and how often the patients fall. This allows clinicians to understand the patient’s muscle function. In this study, the cachexia staging score was testing in patients with advanced cancer who are receiving palliative care, to assess its usefulness in these patients. Here, the cachexia staging score was excellent at predicting life expectancy in the patients with advancing cancer receiving palliative care, and was able to classify patients according to their different stages of cachexia. This review by Ueshima J et al. aimed to assess whether the cachexia staging score could be applied to patients with advanced cancer under palliative care.
Cancer cachexia can be mainly categorised with the occurrence of muscle loss, malnutrition and systemic inflammation. Its prognosis can be assessed through the cachexia index, but the use of this index is limited due to it being a complicated procedure with high testing costs. This study explored using a hand grip strength-based cachexia index, testing it with 14, 682 cancer patients. A low hand grip strength index score was found to be associated with high systemic inflammation, high levels of malnutrition and co-morbidities, implying that this index may be associated with disease progression. Overall, using the hand grip strength index for cachexia reflects the muscular and inflammatory conditions of cachexia in one assessment, rather than using multiple such as serum albumin testing, in a simple, non-invasive measure. Furthermore, there is a potential that hand grip strength can provide information about the prognosis of other malignancies.
This review by Xie H et al. aimed to compare the hand grip strength-based cachexia index to the original cachexia index to understand its benefits.