Current Opinion in Supportive and Palliative Care最新文献

Purpose of review: Cachexia is a devasting syndrome which impacts a large number of patients with cancer. This review aims to provide a comprehensive overview of the central mechanisms of cancer cachexia. In particular, it focuses on the role of the central nervous system (CNS), the melanocortin system, circulating hormones and molecules which are produced by and act on the CNS and the psychological symptoms of cancer cachexia.

Recent findings: A growing body of evidence suggests that a central mechanism of action underpins this multi-system disorder. Recent research has focused on the role of neuroinflammation that drives the sickness behaviour seen in cancer cachexia, with emphasis on the role of the hypothalamus. Melanocortin receptor antagonists are showing promise in preclinical studies. There are also new pharmacological developments to overcome the short half-life of ghrelin. GDF-15 has been identified as a core target and trials of compounds that interfere with its signalling or its central receptor are underway.

Summary: Understanding the central mechanisms of cancer cachexia is pivotal for enhancing treatment outcomes in patients. While emerging pharmacological interventions targeting these pathways have shown promise, further research is essential.

Purpose of the review: Cancer-associated cachexia is a wasting syndrome entailing loss in body mass and a shortened life expectancy. There is currently no effective treatment to abrogate this syndrome, which leads to 20-30% of deaths in patients with cancer. While there have been advancements in defining signaling factors/pathways in cancer-induced muscle wasting, targeting the same in the clinic has not been as successful. Krüppel-like factor 10 (KLF10), a transcription factor implicated in muscle regulation, is regulated by the transforming growth factor-beta signaling pathway. This review proposes KLF10 as a potential convergence point of diverse signaling pathways involved in muscle wasting.

Recent findings: KLF10 was discovered as a target of transforming growth factor-beta decades ago but more recently it has been shown that deletion of KLF10 rescues cancer-induced muscle wasting. Moreover, KLF10 has also been shown to bind key atrophy genes associated with muscle atrophy in vitro .

Summary: There is an elevated need to explore targets in cachexia, which will successfully translate into the clinic. Investigating a convergence point downstream of multiple signaling pathways might hold promise in developing effective therapies for cachexia.

Purpose of review: Cachexia is a debilitating condition causing weight loss and skeletal muscle wasting that negatively influences treatment and survival of cancer patients. The objective of this review is to describe recent discoveries on the role of a novel signaling pathway involving ectodysplasin A2 receptor (EDA2R) and nuclear factor κB (NFκB)-inducing kinase (NIK) in muscle atrophy.

Recent findings: Studies identified tumor-induced upregulation of EDA2R expression in muscle tissues in pre-clinical cachexia models and patients with various cancers. Activation of EDA2R by its ligand promoted atrophy in cultured myotubes and muscle tissue, which depended on NIK activity. The non-canonical NFκB pathway via NIK also stimulated muscle atrophy. Mice lacking EDA2R or NIK were protected from muscle loss due to tumors. Tumor-induced cytokine oncostatin M (OSM) upregulated EDA2R expression in muscles whereas OSM receptor-deficient mice were resistant to muscle wasting.

Summary: Recent discoveries revealed a mechanism involving EDA2R-NIK signaling and OSM that drives cancer-associated muscle loss, opening up new directions for designing anti-cachexia treatments. The therapeutic potential of targeting this mechanism to prevent muscle loss should be further investigated. Future research should also explore broader implications of the EDA2R-NIK pathway in other muscle wasting diseases and overall muscle health.

Purpose of review: To explore the contributions of recent qualitative literature in progressing understanding of the experiences of cancer cachexia, and its management, from the perspectives of patients and unpaid/family carers.

Recent findings: Challenges with conducting everyday activities, maintaining independence, and continuing usual roles within the family are sources of distress. Patients and carers value individualization, flexibility, and carer involvement in physical activity/exercise interventions. In psychosocial/educational interventions that were positively perceived, the opportunity to talk about cachexia was appreciated, leading to improved health literacy, awareness about nutrition, and relationships with food. However, the general patient and carer experience around clinical acknowledgement and management of cachexia remains poor.

Summary: Eating-related distress and conflicts, lack of understanding about cachexia, and the visibility of weight loss remain recurring themes amongst literature on experiences of cancer cachexia. Studies exploring preferences for, and experiences of, interventions have primarily focused on physical activity or exercise. Psychosocial/educational and physical activity/exercise interventions are valued and perceived to alleviate some of the key quality of life issues amongst patients with cancer cachexia and their unpaid/family carers.

Purpose of review: Comprehensive supportive care interventions for patients with lung cancer are being investigated in a range of ways, including: early palliative care, prehabilitation and rehabilitation. We review recent literature on supportive care and propose a traffic light system to individualise comprehensive supportive care. Green for those very likely to receive anti-cancer treatment, red for those very unlikely to receive anti-cancer treatment and orange where the chance of accessing treatment is uncertain. Comprehensive supportive care can be individualised based on the group a particular patient is in.

Recent findings: Lung cancer outcomes are improving with the availability of increasingly efficacious treatments; however, treatment rates for advanced disease remain low. In this review, we discuss how person-centred outcomes could be improved, how outcomes can be prognosticated and how the 'host' can be staged as well as the cancer. Recent data suggests that early comprehensive supportive care improves quality of life, reduces time spent in hospital and may affect survival.

Summary: Comprehensive supportive care is likely to improve quality of life in patients with advanced lung cancer. Further work is needed to see if it can improve treatment rates and survival.

Purpose of review: Accurate assessment of dietary intake, especially energy and protein intake, is crucial for optimizing nutritional care and outcomes in patients with cancer. Validation of dietary assessment methods is necessary to ensure accuracy, but the validity of these methods in patients with cancer, and especially in those with cancer cachexia, is uncertain. Validating nutritional intake is complex because of the variety of dietary methods, lack of a gold standard method, and diverse validation measures. Here, we review the literature on validations of dietary intake methods in patients with cancer, including those with cachexia, and highlight the gap between current validation efforts and the need for accurate dietary assessment methods in this population.

Recent findings: We analyzed eight studies involving 1479 patients with cancer to evaluate the accuracy and reliability of 24-hour recalls, food records, and food frequency questionnaires in estimating energy and protein intake. We discuss validation methods, including comparison with biomarkers, indirect calorimetry, and relative validation of dietary intake methods.

Summary: Few have validated dietary intake methods against objective markers in patients with cancer. While food records and 24-hour recalls show potential accuracy for energy and protein intake, this may be compromised in hypermetabolic patients. Additionally, under- and overreporting of intake may be less frequent, and the reliability of urinary nitrogen as a protein intake marker in patients with cachexia needs further investigation. Accurate dietary assessment is important for enhancing nutritional care outcomes in cachexia trials, requiring validation at multiple time points throughout the cancer trajectory.

Purpose of review: Several innovative digital technologies have begun to be applied to diagnosing and treating migraine. We reviewed the potential benefits and opportunities from delivering migraine care through comprehensive digital clinics.

Recent findings: There are increasing applications of digitization to migraine diagnosis and management, including e-diaries, and patient self-management, especially after the COVID-19 pandemic. Digital care delivery appears to better engage chronic migraine sufferers who may struggle to present to physical clinics.

Summary: Digital clinics appear to be a promising treatment modality for patients with chronic migraine. They potentially minimize travel time, shorten waiting periods, improve usability, and increase access to neurologists. Additionally, they have the potential to provide care at a much lower cost than traditional physical clinics. However, the current state of evidence mostly draws on case-reports, suggesting a need for future randomized trials comparing digital interventions with standard care pathways.

Purpose of review: This focused, narrative review mostly describes our team's investigations into the potential inflammatory mechanisms that contribute to the development of cancer-related gastrointestinal (GI) mucositis and its associated symptoms. This review summarizes details of our clinical and preclinical findings to test the role of inflammation in the development and occurrence of these cancer-related conditions.

Recent findings: GI mucositis (GIM) is a common, distressing condition reported by cancer patients. GIM is often clustered with other behaviors including fatigue, pain, anorexia, depression, and diarrhea. It is hypothesized that there is a common biologic mechanism underpinning this symptom cluster. Our multi-platform investigations revealed that GIM and its associated cluster of behaviors may be triggered by local inflammation spreading systemically causing pro-inflammatory-mediated toxicities, leading to alterations in immune, metabolic, and nervous system functions and activities. For example, behavioral toxicities related to local irradiation for non-metastatic cancer may be triggered by mGluR5 activation influencing prolonged T cell as well as NF-κB transcription factor activities. Thus, interventions targeting inflammation and associated pathways may be a reasonable strategy to alleviate GIM and its symptom cluster.

Summary: GIM may be a sign of a broader systemic inflammatory response triggered by cancer or its treatment. Addressing GIM and its associated symptoms primarily involves supportive care strategies focused on relieving symptoms, promoting healing, and preventing complications.

Purpose of review: Mirogabalin is a novel gabapentinoid medication for the treatment of neuropathic pain. The purpose of this review is to discuss current evidence for its use. Gabapentinoids are widely prescribed for neuropathic pain. Mirogabalin offers theoretical advantages over traditional gabapentinoids due to its specificity for the α2δ-1 subunit of voltage-gated calcium channels. It is theorised that this specificity may reduce adverse drug reactions by minimising binding to the α2δ-2 subunit which is responsible for many of the gabapentinoid side effects.

Recent findings: Mirogabalin's slower dissociation from the α2δ-1 compared with α2δ-2, and its higher potency may also impart an efficacy benefit over traditional gabapentinoids. These theoretical advantages of mirogabalin remain inconclusive in clinical practice, with mixed evidence regarding mirogabalin versus traditional gabapentinoids. Some studies suggest a reduced side effect profile yet, others fail to demonstrate significant differences. Regarding efficacy, mirogabalin may be superior to placebo for several neuropathic pain syndromes, but evidence of widespread benefit over traditional gabapentinoids is currently lacking.

Summary: Mirogabalin offers theoretical promise, but large, independent studies are required to further assess its performance versus traditional gabapentinoids.