MADRID – These were the messages delivered by speakers at the annual meeting of the European Society for Medical Oncology during a session titled “The Multiple Faces of Fatigue in the Cancer Ecosystem.”
Cancer-related fatigue is said to affect 40% of patients at the time of cancer diagnosis, 65% of patients during active or maintenance treatment, 21%-52% of patients in the 5 years following cancer diagnosis, and even one quarter of patients who are between 5 and 30 years post diagnosis, said Florian Scotté, MD, PhD, head of the interdisciplinary department for the Organization of Patient Pathways at Gustave Roussy Institute in Villejuif, France.
However, he underlines that “up to 50% of cancer survivors report never having discussed their cancer-related fatigue or received advice or support on how to manage it.”
What exactly is this fatigue? According to the definition set out in the ESMO 2020 recommendations and repeated word for word in the latest recommendations issued by the National Comprehensive Cancer Network published on Oct. 6, cancer-related fatigue is “a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.”
Mechanisms at play
The mechanisms at play in cancer-related fatigue are clinical, molecular, and psychological, stated Dr. Scotté.
In terms of the clinical factors responsible for patients’ fatigue, comorbidities such as anemia, diabetes, heart disease, and even psychological conditions are significant elements. In addition, taking medicinal products such as antidepressants or beta-blockers can also cause fatigue. Furthermore, cancer treatment itself has many possible side effects, such as anemia, hypothyroidism, insomnia, pain, and hypopituitarism.
In terms of molecular and physiologic factors, central nervous system dysfunction (inflammation, hypothalamic-pituitary-adrenal axis) leads to perceived reduced physical and mental capacity with no clear motor or cognitive deficiencies. Changes in the peripheral nervous system also cause reduced energy metabolism, which hampers the response of muscles to stimuli, possibly even limiting endurance. Finally, several studies have shown that systemic inflammation is involved in the onset of fatigue.
Dr. Scotté also highlighted the importance of psychological factors, citing depression, psychosocial stress before treatment, negative attention to symptoms, and fear of relapse as key features in the development of cancer-related fatigue.
Among the risk factors for developing cancer-related fatigue, the speaker mentioned a combination of genetic, psychological, and biobehavioral factors (such as preexisting risk factors, depression, sleep disorders, physical inactivity, BMI, smoking, alcohol consumption, and adaptability).
Screen and diagnose
“Cancer-related fatigue is one of the most underestimated and least researched side effects,” said Christina Ruhlmann, MD, PhD, an oncology consultant at Odense (Denmark) University Hospital. “It is important to screen for fatigue in cancer patients.”
There are several tools available to enable this screening, she noted. The EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30) is a three-item subscale evaluating the symptoms of fatigue, weakness, and lack of energy. The MD Anderson Symptom Inventory (13 items) assesses fatigue, sleep disorders, and drowsiness. The numeric rating scale (NRS) for fatigue is an 11-point visual self-assessment scale comprising a single element, with 0 representing no fatigue and 10 representing intense fatigue.
When screening for cancer-related fatigue, whenever a score of 4 or more is obtained on the NRS, a diagnostic assessment is needed based on clinical history-taking, fatigue assessment, and evaluation of comorbidities.
When taking the clinical history, information should be obtained on the type of condition, its stage, any relapse or progression, metastases, the date of diagnosis, length of treatment, any cancer or surgical treatments carried out, other treatments administered, and the risk for drug interactions.
In addition, to assess fatigue, the diagnostic process consists of documenting the start, type, and duration of the fatigue, as well as the presence of attenuating factors and interference with activities of daily living and leisure activities.
Seeking information regarding environmental factors such as availability of a support network of family and friends or financial resources is also paramount, said Dr. Ruhlmann.
Finally, contributory factors that may require treatment must be assessed. They include pain, emotional distress, anemia, sleep disorders, nutritional deficiencies, inactivity, smoking and alcohol consumption, and comorbidities (such as cardiac, endocrine, gastrointestinal, hepatic, infectious, and renal conditions).
The following two simple questions can be used to screen for symptoms of depression quickly:
- Over the past month, have you often felt despondent, sad, depressed, or in despair?
- Over the past month, have you found less pleasure than usual in doing the things you normally enjoy doing?
How to treat?
“All of the elements associated with fatigue that can be taken into account ought to be,” stressed Dr. Ruhlmann before insisting on the key role played by physical activity in combating the feeling of exhaustion.
The ESMO recommendations indicate that, according to the results of randomized clinical trials and systematic literature reviews, physical exercise can be recommended in patients with cancer who do not have cachexia (level of evidence I, B).
The type of physical activity recommended is moderate, aerobic, and functional strength exercises (I, B). Walking, aerobic exercises at home, and strength exercises are recommended to improve cancer-related fatigue and quality of life (II, B). “They help with fatigue and also with side effects such as depression, anxiety, pain, and muscle strength,” said Dr. Ruhlmann.
Alongside exercise, and with a lower level of evidence, pharmacologic treatments can sometimes be used (II, B; II, D). Short-term use of dexamethasone or methylprednisolone is recommended for managing fatigue linked to metastatic cancer except during the course of immunotherapy (II, B).
The ESMO expert group did not reach a consensus on the use of methylphenidate, dexmethylphenidate, slow-release methylphenidate, and dexamphetamine.
Modafinil and armodafinil, antidepressants (especially paroxetine), donepezil and eszopiclone, megestrol acetate, and melatonin are not recommended (II, D).
No consensus could be reached on nutraceuticals, and they are not recommended, said Dr. Ruhlmann (II, C; II, D).
Finally, psychosocial interventions in the form of information, advice, psychoeducation, and cognitive-behavioral therapy are useful tools (II, B).
Another area being explored is the gut microbiota. “Research into the microbiota and its role in systemic inflammation is underway and could pave the way for future strategies for managing cancer-related fatigue,” said Dr. Ruhlmann. “Fatigue is a subjective experience, unlike other symptoms. It’s what those people suffering from it say it is!”
This article was translated from the Medscape French edition.