Cancer Cachexia: Understanding Weight Loss and Muscle Wasting Associated with Cancer
What
is Cancer Cachexia?
Cancer
cachexia is a complex metabolic syndrome associated with underlying illness
and characterized by loss of muscle with or without loss of fat mass. It
commonly affects patients with advanced cancer leading to significant weight
loss, muscle wasting, fatigue and weakness. It severely impacts patients'
quality of life and response to treatment. Its presence is often an indication
of poor prognosis in cancer patients.
Mechanisms
The exact mechanisms leading to it are not fully understood but are thought to
be triggered by a combination of tumor and host factors. Tumors often secrete
various inflammatory factors, metabolic hormones and metabolic wastes which
have catabolic effects on host tissues like muscle and fat. Key factors
released by tumors and immune cells like pro-inflammatory cytokines,
proteolysis-inducing factor (PIF) and lipid mobilizing factor have been shown
to activate metabolic pathways responsible for increased muscle and fat
breakdown. Cancer patients also experience chronic stress and oxidative stress
response which further aggravates catabolism and suppresses protein synthesis
in muscles. Anti-inflammatory cytokines like IL-6 and TNF-alpha are thought to
mediate these catabolic effects on body tissues.
Clinical Features and Diagnosis
Cancer cachexia is clinically apparent as unintended weight loss of 5% or
more over past 6 months or muscle wasting evident from sarcopenia on medical
imaging. Loss of subcutaneous fat and thinning of facial features are commonly
seen. Patients experience reduced muscle strength, fatigue, weakness, abdominal
fullness and early satiety. Standard blood panel may show signs of inflammation
like elevated CRP and tumor markers. Dual energy X-ray absorptiometry (DEXA)
scan and computed tomography (CT) images help quantify muscle and fat loss.
Diagnosis is made after ruling out other potential causes and considering
clinical context of underlying malignancy and systemic symptoms.
Impact on Treatment and Outcomes
The metabolic abnormalities associated with cachexia lead to reduced
chemotherapy tolerance, increased toxicity risk and impediment of cancer
therapies. Cachectic patients are more prone to chemotherapy dose reductions or
delays due to poor nutritional status and toxicity. Cachexia adversely impacts
response to immunotherapy treatments as well. Cachexia is an independent
negative prognostic factor and its presence often signifies advanced,
refractory disease. It contributes to increased treatment related morbidity and
mortality in cancer patients. Management of it is crucial for optimizing cancer
treatment delivery, tolerance and outcomes for patients.
Management Approaches
Currently there is no U.S. Food and Drug Administration approved drug
specifically for cancer cachexia and management focuses on multimodal
supportive care. Nutritional counseling, high calorie diet plans, appetite
stimulants, nutritional supplementation, exercise programs, treatment of
underlying infection and inflammation, corticosteroids and androgen therapy
have shown some benefit in improving nutritional status and reversing cachexia.
Emerging growth factor based anabolic therapies targeting myostatin, activin
receptors, glucocorticoids and select cytokines are under active research.
However, the complex pathophysiology and multifactorial etiology of it pose
challenges in developing targeted therapies. Palliative care input, symptom
control and improvement of quality of life assume priority over body weight goals
for advanced stage patients with cachexia. Prognosis often remains guarded
despite aggressive supportive measures.
Future Directions
Deeper understanding of molecular and metabolic pathways dysregulated in
cachexia is essential to develop new targeted pharmacologic interventions.
Promising therapeutic avenues are appetite stimulants modulating ghrelin
signaling, cannabinoid receptor agonists, anti-inflammatory agents,
anti-oxidants, EPA/DHA supplements, angiotensin and ghrelin receptor
modulators, myostatin and ActRII inhibitors. Combination therapies targeting
multiple drivers of muscle wasting simultaneously may prove more effective than
single agent approaches. Identifying pre-cachectic or early cachexia stages
could help initiate interventions earlier for better impact. Developing
validated assessment tools to monitor cachexia progression or response is
needed. Improved inter-professional models integrating oncology, palliative
care, nutrition and rehabilitation are warranted to maximize supportive care
benefits for cachectic cancer patients.
Conclusion
In summary, cancer cachexia is a debilitating systemic syndrome associated
with significant morbidity, reduced quality of life and poor oncologic outcomes
in cancer patients. Its complex pathogenesis still remains incompletely
understood. Current management strategy focuses on multi-modal nutrition
intervention, symptom control and palliation given the limited efficacy of
existing pharmacologic options. Continued translational research into the molecular
drivers of cachexia and development of novel combination anabolic therapies
hold promise to better combat this condition in future. Integrated supportive
care models optimizing management of cachexia throughout the cancer continuum
also warrant further exploration. Addressing the challenges of cancer cachexia
can potentially improve tolerance of oncologic interventions, clinical outcomes
and quality of remaining life for affected patients.
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1. Source:
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