Multidisciplinary approaches to cancer cachexia: current service models and future perspectives.

INTRODUCTION: Cancer cachexia remains a complex unmet need in oncology, despite its high prevalence and high impact. Patients with cachexia experience numerous complications, including reduced tolerance and effectiveness of anti-cancer therapy, reduced mobility, and reduced functional status, leading to decreased quality of life and survival. AREAS COVERED: As the field moves toward greater consensus of definitions and measurements, we highlight tools currently available for identification and staging of cachexia, and the barriers that people with cancer face in timely identification and management of cachexia. Multidisciplinary cachexia service models have emerged to address practice gaps and needs identified by patients and clinicians. Person-centred approaches to cachexia care demonstrate promising improvements in patient outcomes, but controlled trials of service models are lacking. EXPERT OPINION: While significant advances have been made in the understanding of cachexia, future trials of clinical service models require standardisation of definitions and outcome measures, with more robust controlled studies to establish the efficacy of proposed best practice. We remain excited with the potential benefit of these innovative models and continue to advocate for implementation of dedicated multidisciplinary cachexia teams to ensure patients and their families receive the right support, in the right place, at the right time.

Evaluation of a Multidisciplinary Cachexia and Nutrition Support Service- The Patient and Carers Perspective.

The Barwon Health Cachexia & Nutrition Support Service (CNSS) is an outpatient service focused on improving clinical outcomes and quality of life for patients with or at high risk of cancer cachexia. Patients see a multidisciplinary team, comprising a palliative medicine physician, physiotherapist, dietitian, and nurse practitioner. This study evaluated the service from patient and carer perspectives. In 2016/17, semistructured interviews were conducted with 12 patients and 9 carers attending the service, focusing on: (1) reflection on experience of the CNSS, and (2) describing how a cachexia-specific service can meet their needs and concerns. Analysis generated 4 superordinate themes: evolving perception of service value, empowerment through person-centered care, communication to patients and carers regarding health/disease information, and the importance of the multidisciplinary team-based approach. Generally, patients and carers reported overall positive experiences with the service, particularly with regard to improved communication and management of the patient. Findings confirmed the patient-centered and individualized approaches were particularly valued. These insights are a critical step in the development of recommendations for future clinical management of cancer cachexia.

Defining a new model of interdisciplinary cancer cachexia care in regional Victoria, Australia.

PURPOSE: Cachexia is a wasting condition affecting approximately 50% of cancer patients, associated with decreased quality of life and survival. Barwon Health's Cachexia and Nutrition Support Service provides person-centred interdisciplinary care to assist the management of cachexia symptoms. This study describes a novel and effective service model established in a regional cachexia clinic and the patient population it serves. METHODS: A descriptive, retrospective longitudinal study was conducted of records from patients attending Barwon Health between 2008 and 2013 (n = 175), alongside the description of service refinement over this time. Patients with ≥ 2 attendance dates were assessed for anthropometric measures, follow-up intervals, and muscle function outcomes to describe patient trajectory during clinic involvement. RESULTS: This is the first detailed description of a successful interdisciplinary clinic specific to cancer cachexia management, where patients are seen outside established 8- to 12-week structured programs which prevail in other cachexia clinics. Seventy-five patients (43%) attended one appointment only, with almost half of these (n = 33) first attending within 60 days of death. Of the 99 patients with two or more appointments, 49% displayed positive outcomes with > 2-kg weight gain between two consecutive appointments, and > 50% improved functional strength between two consecutive appointments. CONCLUSIONS: The majority of patients attending clinic multiple times maintained or increased weight and functional status during their involvement with the service. However, successes of care provision were muted by high attrition, primarily due to delayed referral and expected high mortality within the study cohort. Planned future analyses with greater patient numbers and cancer stratification will establish cachectic populations most likely to benefit from this novel mode of interdisciplinary care. The Cachexia and Nutrition Support Service provides an effective and efficient service model for the provision of specialist cachexia care to community-dwelling patients in regional Australia.

Cancer cachexia: impact, mechanisms and emerging treatments.

Many forms of cancer present with a complex metabolic profile characterised by loss of lean body mass known as cancer cachexia. The physical impact of cachexia contributes to decreased patient quality of life, treatment success and survival due to gross alterations in protein metabolism, increased oxidative stress and systemic inflammation. The psychological impact also contributes to decreased quality of life for both patients and their families. Combination therapies that target multiple pathways, such as eicosapentaenoic acid administered in combination with exercise, appetite stimulants, antioxidants or anti-inflammatories, have potential in the treatment of this complex syndrome and require further development.

Eicosapentaenoic acid and oxypurinol in the treatment of muscle wasting in a mouse model of cancer cachexia.

Cancer cachexia is a wasting condition, driven by systemic inflammation and oxidative stress. This study investigated eicosapentaenoic acid (EPA) in combination with oxypurinol as a treatment in a mouse model of cancer cachexia. Mice with cancer cachexia were randomized into 4 treatment groups (EPA (0.4 g/kg/day), oxypurinol (1 mmol/L ad-lib), combination, or control), and euthanized after 29 days. Analysis of oxidative damage to DNA, mRNA analysis of pro-oxidant, antioxidant and proteolytic pathway components, along with enzyme activity of pro- and antioxidants were completed on gastrocnemius muscle. The control group displayed earlier onset of tumor compared to EPA and oxypurinol groups (P<0.001). The EPA group maintained body weight for an extended duration (20 days) compared to the oxypurinol (5 days) and combination (8 days) groups (P<0.05). EPA (18.2±3.2 pg/ml) and combination (18.4±3.7 pg/ml) groups had significantly higher 8-OH-dG levels than the control group (12.9±1.4 pg/ml, P≤0.05) indicating increased oxidative damage to DNA. mRNA levels of GPx1, MURF1 and MAFbx were higher following EPA treatment compared to control (P≤0.05). Whereas oxypurinol was associated with higher GPx1, MnSOD, CAT, XDH, MURF1, MAFbx and UbB mRNA compared to control (P≤0.05). Activity of total SOD was higher in the oxypurinol group (32.2±1.5 U/ml) compared to control (27.0±1.3 U/ml, P<0.01), GPx activity was lower in the EPA group (8.76±2.0 U/ml) compared to control (14.0±1.9 U/ml, P<0.05), and catalase activity was lower in the combination group (14.4±2.8 U/ml) compared to control (20.9±2.0 U/ml, P<0.01). There was no change in XO activity. The increased rate of weight decline in mice treated with oxypurinol indicates that XO may play a protective role during the progression of cancer cachexia, and its inhibition is detrimental to outcomes. In combination with EPA, there was little significant improvement from control, indicating oxypurinol is unlikely to be a viable treatment compound in cancer cachexia.