Attention to cancer-related physical and mental fatigue: Breaking the vicious cycle

Abstract

Cancer-related fatigue (CRF) presents as a complex interplay between physical and mental fatigue, with mindfulness interventions offering a promising approach to alleviate both. These techniques, including mindfulness-based stress reduction, cognitive therapy, dialectical behavior therapy, and acceptance and commitment therapy, are designed to break the cycle of CRF by addressing its psychological and emotional aspects. This editorial integrates the latest research published by Liu et al, examining the reciprocal and harmful cyclical relationship between physical and mental CRF, and explores the causes and associated mindfulness interventions. We expect that future research will emphasize the identification and management of CRF, particularly focusing on the application of various mindfulness interventions in cancer survivors and patients undergoing cancer treatment, as well as the development of mindfulness in the era of new technologies.

Key Words: Cancer-related fatigue; Physical fatigue; Mental fatigue; Mindfulness; Mindfulness interventions; Cancer management

Core Tip: Effective management of cancer-related fatigue (CRF) is imperative, particularly given its association with poor health-related quality of life and functional disruptions. Mindfulness interventions are explored as a means to break the cycle of physical and mental CRF, potentially enhancing the well-being and survival of cancer patients. Mindfulness interventions, including mindfulness-based stress reduction, cognitive therapy, dialectical behavior therapy, and acceptance and commitment therapy, are effective in alleviating CRF by addressing both physical and mental aspects, disrupting the cycle of fatigue and improving the quality of life for cancer survivors.

INTRODUCTION

Despite the increase in the 5-year relative survival rate for all cancers combined from 49% in the mid-1970s to 68% between 2012 and 2018, cancer remains a significant global public health challenge[1]. The quality of life issues faced by cancer survivors, which accompany advancements in cancer treatment, increasingly demand attention[2,3]. Among these concerns, cancer-related fatigue (CRF) has consistently been a significant issue for both patients and healthcare providers. CRF refers to a distressing, persistent, and subjective sensation of physical, emotional, and/or cognitive tiredness associated with cancer and/or its treatment, which hampers normal functioning and does not correlate with recent activity levels[4]. A meta-analysis involving 144813 patients indicated that the overall pooled prevalence of CRF was estimated to be 52%[5]. CRF is closely associated with impaired health-related quality of life (HRQOL) and severe disruptions in social and occupational functioning during various stages of cancer survivorship[6,7]. Therefore, there is an urgent need to manage CRF effectively. Physical and mental CRF are the two predominant aspects of CRF, and they mutually influence each other. Exploring effective ways to break the vicious cycle caused by the interaction of physical and mental CRF may be one of the effective methods to improve CRF. Consequently, this could also be expected to enhance the HRQOL and survival time of those undergoing tumor treatment and cancer survivors.

We are interested in two forthcoming articles in the World Journal of Psychiatry. The authors focus on leukemia patients and patients with large B-cell lymphoma, respectively, and both studies have found that emotional state significantly impacts CRF[8,9]. One of the above studies also examined the influence of subthreshold depressive symptoms, which is prevalent in many cancer patients but often overlooked, on CRF and treatment complications[8]. We gratefully acknowledge the valuable contributions made by the authors above to the study of CRF. Inspired by the articles mentioned above, this editorial endeavors to investigate solutions for addressing CRF by disrupting the detrimental cycle between physical and mental CRF through mindfulness interventions.

VICIOUS CYCLE BETWEEN PHYSICAL AND MENTAL CRF

Cancer-related physical fatigue is characterized as a distressing, persistent, and subjective sense of physical tiredness or exhaustion associated with cancer or its treatment. This form of CRF is disproportionate to the patient’s recent activity level and does not abate with rest[10]. It is a distinct aspect of CRF, focusing solely on the physical dimension of exhaustion experienced by cancer patients, which can be debilitating and persist throughout and beyond the treatment period. On the other hand, cancer-related mental fatigue represents another primary source and manifestation of CRF, focusing on the psychological and emotional aspects of exhaustion experienced by cancer patients. Physical and mental CRF manifest distinctively[11]. Previous research has found that even if physical symptoms improve, psychological stress in cancer survivors may persist for a long time after treatment[12]. Furthermore, all cancer-related symptoms and HRQOL variables are closely associated with mental health status. Therefore, it is recommended to develop targeted and routine interventions for mental CRF in patients[13].

Two forms of CRF, physical and mental, are not isolated entities but are deeply interconnected, creating a cycle that can be challenging to break. First, the physical symptoms of cancer, such as pain, nausea, and weakness, can lead to emotional distress and mental fatigue[2]. In addition, the physical demands of cancer treatment, such as chemotherapy and radiation therapy, can also exacerbate physical fatigue and the mental fatigue that follows[5]. This cancer-related physical fatigue, in turn, can exacerbate mental health issues, such as depression and anxiety, which further contribute to mental fatigue. The mental exhaustion experienced by patients can then impair their ability to engage in physical activities, perpetuating the cycle of physical and mental CRF[14,15]. The cycle continues as the individual becomes increasingly debilitated, leading to a decline in overall quality of life.

Understanding this vicious cycle of fatigue that cancer patients may experience is crucial for developing comprehensive strategies to alleviate CRF and enhance the HRQOL for these patients. Breaking this cycle necessitates a multifaceted approach, which entails early identification and adoption of integrated strategies to address CRF’s physiological and psychological dimensions. Focusing solely on one aspect, as is still prevalent in current cancer management, which primarily focuses on the physical aspects of CRF while neglecting the mental aspects, including subthreshold depressive symptoms, is likely to perpetuate the vicious cycle of fatigue, leading to prolonged suffering for cancer patients and potentially increasing the risk of complications[8].

PHYSICAL AND MENTAL CRF: UNDERSTANDING THE CAUSES

Reference Citation Analysis (RCA, https://www.referencecitationanalysis.com/) is a unique artificial intelligence system for evaluating citations in the biomedical literature. We used RCA to analyze previous studies up to June 2024 on high-risk factors, mechanisms, and interventions for CRF. The first step in addressing CRF is to identify the underlying causes. Previous studies have identified a series of high-risk factors that may contribute to the development of CRF and impact its severity. These factors include the type and stage of cancer, the intensity of cancer treatments such as chemotherapy and radiation therapy, and the presence of other comorbid conditions (such as pain, low levels of physical activity, poorly controlled chronic diseases, sleep disorders, anxiety, and depression)[5,16]. Among the psychosocial risk factors, childhood adversity is also a strong and consistent predictor of CRF[17]. Additionally, demographic factors such as age, gender, and socioeconomic status may also play a role in the development of CRF[18]. Based on the abovementioned findings, constructing and validating predictive models for CRF has become a hot topic in recent research[19,20]. After all, the early detection of the aforementioned high-risk factors in cancer patients and the individualized prediction of the risk of CRF occurrence are necessary to initiate timely intervention measures. Therefore, it also represents the first step in improving the current management of CRF.

Recent studies have also honed in on the potential mechanisms underlying CRF. Several studies have explored the role of inflammation, immune dysfunction, and alterations in energy metabolism in the pathogenesis of CRF. Cancer itself, along with treatment-related dysfunctions of bones, muscles, and mitochondria, peripheral immune activation, inflammatory dysfunction, and the resulting imbalances in protein and energy metabolism, as well as neurological dysfunction, are all closely associated with the occurrence and development of CRF[21-23]. Additionally, studies have reported that CRF can be improved by regulating the gut microbiota-gut-brain axis[24]. By advancing the understanding of CRF, we can improve the HRQOL for cancer survivors and enhance their recovery. However, the current scarcity of appropriate animal models poses a challenge for unraveling the molecular mechanisms of CRF. Consequently, future research may benefit from developing more precise animal models that mimic human CRF, enabling a deeper investigation into its underlying molecular pathways.

Furthermore, research has also investigated the efficacy of various interventions, including pharmacological treatments, exercise, cognitive-behavioral therapy (CBT), and mindfulness-based intervention techniques, in alleviating CRF symptoms[25,26]. Interventions for CRF can be categorized into pharmacological and non-pharmacological approaches. Pharmacological interventions may include the use of stimulants, antidepressants, traditional Chinese medicine, and other medications to alleviate symptoms of fatigue[27]. Non-pharmacological interventions include exercise, CBT, and mindfulness-based intervention techniques[28]. A comprehensive approach combining pharmacological and non-pharmacological interventions may be more effective in managing CRF. Future research should focus on more effective interventions that contribute to the vicious cycle between physical and mental CRF. Efforts should be made to standardize intervention measures in real-world practice to promote their widespread adoption and help more cancer survivors improve their HRQOL and extend their survival duration.

MINDFULNESS INTERVENTIONS FOR PHYSICAL AND MENTAL CRF

Mindfulness, an ancient meditative practice, refers to focusing on the present moment with an accepting mindset, and it is associated with engagement in various health-enhancing behaviors[29]. Previous research revealed that among the multiple factors related to CRF, such as mindfulness, anxiety, depression, loneliness, pain, and sleep disturbances, mindfulness exerted the most significant influence on fatigue. Moreover, mindfulness not only had a direct impact on fatigue but also moderated its effects indirectly through the channels of anxiety, depression, loneliness, pain, and sleep disorders[30]. Considering the profound influence that an individual’s level of mindfulness and related skills exert on their emotional states and behaviors, a range of mindfulness-oriented training and intervention approaches have been developed. These include mindfulness-based stress reduction (MBSR), mindfulness-based cognitive therapy (MBCT), mindfulness-based dialectical behavior therapy (MDBT), and mindfulness-based acceptance and commitment therapy (MACT)[31,32].

Whereas the interplay between physical and mental CRF establishes a relentless and detrimental cycle, mindfulness interventions have emerged as a viable strategy to dismantle this cycle. The mechanism of action involves a range of mindfulness techniques that successfully mitigate the physical and mental fatigue encountered by cancer patients. These interventions tackle the immediate symptoms of physical and mental fatigue while preventing the recurrence of physical fatigue caused by mental fatigue and vice versa. In this manner, they disrupt the physical and mental fatigue cycle, preventing its perpetuation and worsening, effectively halting the vicious cycle and fostering recovery. The following section will explore the diverse mindfulness-based techniques commonly used to alleviate CRF.

MBSR is a foundational intervention that teaches patients to cultivate mindful awareness through meditation, body scanning, and gentle yoga[33]. By focusing on the present moment and adopting a non-judgmental attitude, patients can reduce stress and anxiety, which are known contributors to the perpetuation of both physical and mental fatigue. Studies have shown that MBSR can lead to improved sleep quality, overall well-being, and reduced fatigue levels among cancer survivors, effectively breaking the cycle of CRF[34,35]. As mental fatigue diminishes, physical energy and resilience often follow suit[36].

MBCT combines mindfulness and CBT principles[37]. It was developed as a relapse prevention program to help individuals who are at high risk of experiencing recurrent depression. MBCT aims to teach participants skills to maintain long-term mental well-being by fostering an awareness of the present moment and altering negative thinking and behavior patterns. MBCT’s proposed mechanism is enhanced disengagement from automatic, maladaptive cognitive processes[38]. Awareness of these processes and learning to disengage help patients avoid a cycle of rumination that could exacerbate mental fatigue. Studies indicate that MBCT is particularly effective in addressing mental fatigue, such as depression and anxiety, thereby alleviating mental fatigue and the subsequent physical fatigue, gradually breaking the cycle of fatigue between body and mind[39].

MDBT is another approach that has shown promise in cancer care. MDBT combines mindfulness practices with skills training in emotion regulation and distress tolerance[40,41]. By fostering emotional resilience and enhancing distress tolerance skills, MDBT empowers patients to break free from the cycle of fatigue that negative emotional states and strained relationships can perpetuate. This comprehensive intervention can be particularly beneficial for patients experiencing severe CRF, as it equips them with strategies to manage their emotions and improve their coping mechanisms, ultimately breaking the cycle of fatigue[42]. Through MDBT’s regulation of the emotional roots of mental fatigue, the resulting mental clarity and emotional regulation not only alleviate psychological distress but also indirectly help to reduce the physical symptoms of fatigue, thereby contributing to alleviating the vicious cycle between mental and physical exhaustion.

MACT incorporates acceptance and commitment therapy and mindfulness, focusing on accepting uncomfortable thoughts and feelings as part of the human experience[43]. Despite fatigue, MACT encourages patients to commit to actions that align with their values. MACT allows rather than minimizes cancer-related pain and the fear of cancer recurrence and also helps patients explore their values and sources of meaning. The MACT intervention teaches anxious cancer survivors to break free from rigid, restrictive thoughts and beliefs about themselves and their cancer experience and to commit to engaging in meaningful life activities that align with their values[44]. Through this process, patients are empowered to engage in meaningful activities, thereby enhancing their quality of life. They achieve guided self-help for psychological distress and cultivate positive mental health, effectively disrupting the cycle of CRF[45]. As patients learn to accept and manage their mental fatigue, their physical energy levels gradually improve[46].

Lastly, we noted reports on developing mindfulness applications in the new era. For instance, tailored mobile applications integrating mindfulness with exercise can further enhance patients’ CRF and well-being[47]. Among the various aspects of mindfulness (conscious action, description, non-judgment, and non-reaction), the effective mechanism of online mindfulness interventions for fatigue and sleep issues is primarily achieved through conscious action[48]. In terms of neural mechanisms, although previous studies have suggested that neural circuits involving the prefrontal cortex, anterior cingulate cortex, amygdala, and insula may be involved in the specific processes of mindfulness-based emotional regulation[49], research on how mindfulness interventions affect the perception of fatigue symptoms is relatively limited[50]. Recent studies built on the above foundation have found that when mindfulness meditation predominates over bottom-up processing through sensory stimuli from the external environment, amygdala activity increases through the insula and anterior cingulate cortex activation[51]. However, the dose-response relationship of mindfulness interventions in modulating fatigue remains to be further explored[52].

In summary, mindfulness interventions offer a promising avenue for addressing the complex nature of cancer-related physical and mental fatigue. By fostering a state of mindful awareness and equipping patients with coping strategies, these mindfulness interventions have the potential to break the cycle of CRF and improve the overall well-being of cancer survivors. Future research should continue to explore the specific applications and detailed mechanisms of these mindfulness interventions in cancer management, which includes further investigating how physical and mental CRF interact from a neurophysiological perspective and how mindfulness interventions can be conducted effectively by new technologies such as virtual reality and short video clips, considering user habits.

CONCLUSION

In conclusion, mindfulness interventions provide valuable strategies for addressing cancer-related physical and mental fatigue by breaking their vicious cycle, thus warranting more comprehensive application in patients with various types of cancer to improve their CRF, HRQOL, and survival duration.