Fatigue

Cancer-related fatigue (CRF) is among the most prevalent and distressing symptoms reported by patients, affecting up to 80% of individuals undergoing treatment [15]. Unlike typical fatigue, CRF is persistent, not relieved by rest, and significantly interferes with daily functioning. The pathophysiology is multifactorial, involving inflammatory cytokines, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, anemia, and mitochondrial dysfunction [16]. CRF can persist long after treatment has ended, particularly in survivors of breast, lung, and colorectal cancers.

Nausea and vomiting

Despite the advent of advanced antiemetic regimens, nausea and vomiting remain common side effects of chemotherapy, radiotherapy, and some forms of immunotherapy. Acute nausea typically occurs within 24 h of treatment, while delayed nausea can persist for several days, impairing nutritional intake and adherence to treatment [17]. The anticipatory component—triggered by psychological conditioning—further complicates symptom control. Nausea is also reported in advanced disease due to gastrointestinal obstruction, opioid use, or tumor-related factors.

Sleep disorders

Sleep disturbances, including insomnia, fragmented sleep, and circadian rhythm disruption, affect approximately 30–70% of cancer patients [18]. Contributing factors include corticosteroid therapy, pain, anxiety, and environmental conditions during hospitalization. Poor sleep exacerbates fatigue, cognitive impairment, and emotional distress. Moreover, persistent sleep dysfunction during survivorship is linked to increased risk of depression and reduced immune surveillance [19].

Anxiety and depression

Emotional distress is a frequent and underdiagnosed issue among oncology patients. Up to 20% experience clinically significant anxiety and/or depression during their illness trajectory [20]. Anxiety may be heightened during diagnosis, treatment initiation, and recurrence, while depression often emerges in the context of physical decline, social isolation, or existential distress. Both conditions are associated with poorer treatment adherence, diminished immune function, and increased mortality risk [21].

Pain

Cancer-related pain is reported by approximately 59% of patients receiving active treatment and 64% of those with advanced disease [22]. It may stem from tumor invasion of tissues, treatment-induced neuropathy, or musculoskeletal complications due to immobility or surgery. While opioids are a cornerstone of pain management, they are not always practical or well-tolerated, prompting interest in integrative modalities that may provide adjunctive benefit.

Caregiver burden and burnout

Informal caregivers—typically spouses, adult children, or close relatives—play a critical role in managing the physical, emotional, and logistical needs of cancer patients. However, this responsibility often comes at the cost of the caregiver’s well-being. Commonly reported challenges include chronic stress, emotional exhaustion, sleep deprivation, and social isolation [4, 23]. Caregiver burden is particularly pronounced in palliative and end-of-life care settings. Studies indicate that 30–50% of caregivers exhibit symptoms of clinical depression or anxiety, and many report poorer physical health outcomes compared to non-caregiving peers [24].

The bidirectional relationship between patient and caregiver distress underscores the need for supportive care strategies that address both populations simultaneously. Interventions focused on symptom control, emotional support, and caregiver education are crucial for maintaining quality of life and preventing long-term psychological sequelae.

Aromatherapy

Aromatherapy, the therapeutic use of plant-derived essential oils, has gained increasing recognition as a complementary approach in oncology care [25, 26]. Its non-invasive nature, ease of administration, and relatively low cost make it particularly suitable for cancer settings, where patients often experience multiple symptoms concurrently and may have limited tolerance for additional pharmacologic interventions. Aromatherapy has shown potential in alleviating a range of cancer-related symptoms, including anxiety, nausea, pain, and sleep disturbances [27–30].

Massage therapy

Massage therapy is one of the most widely accepted and utilised complementary interventions in oncology, with a growing body of evidence supporting its role in enhancing quality of life, alleviating symptom burden, and promoting a sense of well-being. It involves the manual manipulation of soft tissues to promote relaxation, reduce tension, and relieve discomfort. In cancer care, massage therapy has been used to address both physical symptoms, such as pain and fatigue, and psychological concerns, including anxiety and depression.

Mindfulness and guided imagery

Mindfulness-based interventions (MBIs) and guided imagery are cognitive-behavioral mind-body techniques that offer scalable, non-invasive tools to reduce psychological distress in both cancer patients and their caregivers. These interventions are especially relevant in oncology settings where individuals face emotional burden, treatment-related anxiety, uncertainty, and caregiver fatigue. Unlike some complementary therapies, mindfulness and guided imagery require no physical equipment or pharmacological agents. They can be easily delivered through brief, structured sessions or mobile applications, making them accessible in clinical, home, or virtual environments.

Music and art therapy

Music therapy and art therapy are expressive, non-pharmacological interventions that support the emotional, cognitive, and spiritual well-being of cancer patients and caregivers. Both modalities are adaptable to a wide range of clinical settings and patient needs, offering accessible tools to process emotions, reduce stress, and foster meaning-making throughout the cancer trajectory.

Sleep hygiene & relaxation techniques

Sleep disturbances are among the most common and debilitating symptoms experienced by cancer patients and their caregivers. Insomnia affects up to 75% of individuals undergoing cancer treatment and often persists into survivorship or end-of-life care [19]. Poor sleep quality is associated with fatigue, impaired cognitive function, reduced treatment adherence, and diminished overall quality of life. It can also exacerbate anxiety and depressive symptoms, creating a self-reinforcing cycle of psychological and physical burden. Importantly, caregivers are also at heightened risk for chronic sleep disruption due to stress, nighttime caregiving responsibilities, and anticipatory grief.

Sleep hygiene education and relaxation-based interventions offer evidence-based, low-cost strategies to mitigate sleep problems in oncology populations. These methods are accessible and adaptable to clinical and home settings, and can be taught as part of routine supportive care without the risks associated with pharmacologic sedatives.

Contraindications and safety considerations across interventions

While non-pharmacological interventions are generally considered safe and well-tolerated, it is essential to recognize that each modality carries specific risks, limitations, and contraindications that must be considered during clinical implementation [102]. A careful, individualized assessment is necessary to avoid unintended harm, particularly in oncology populations who may be medically fragile, immunocompromised, or emotionally vulnerable.

Aromatherapy is widely used for symptom relief; however, the topical application of essential oils may cause skin irritation or allergic reactions, particularly in patients with compromised skin integrity due to radiation or chemotherapy [103, 104]. Essential oils with high phenolic content (e.g., clove, cinnamon) should be avoided in frail or pediatric patients [105]. Photosensitizing essential oils, such as Citrus aurantium, should not be applied before sun exposure [106]. Inhalation is typically safer; however, individual scent aversions and potential interactions with respiratory conditions (e.g., asthma) should be considered.

Massage therapy is contraindicated in patients with severe thrombocytopenia, neutropenia, deep vein thrombosis, active infections, or unstable bone metastases [107]. Oncology-trained therapists should modify techniques to avoid tumor sites, surgical wounds, lymphedema risk areas, and indwelling medical devices. Even a light touch must be carefully adapted to the patient’s tolerance and clinical condition [108].

Mindfulness and guided imagery are highly beneficial for many patients but may pose psychological risks for those with unresolved trauma, dissociative symptoms, or severe emotional instability [109]. Mindfulness practices that involve extended silence or body scanning can inadvertently trigger flashbacks or anxiety. In such cases, trauma-informed adaptations (e.g., anchoring to external stimuli or limiting exposure) are strongly recommended, and a trained facilitator with mental health expertise should ideally introduce practices [110].

Music and art therapy are generally low-risk, but care must be taken in individuals with sound sensitivities, cognitive impairments, or difficulty with sensory processing [111]. Emotionally evocative activities, such as legacy projects or autobiographical art, may stir distress and should be guided by trained professionals who can offer appropriate containment and support [112].

Sleep hygiene and relaxation techniques, including PMR and breathwork, are safe for most patients. However, interventions such as sleep restriction (as part of CBT-I) may not be suitable for individuals with severe fatigue, advanced disease, or cognitive impairment [113]. Additionally, some patients may find the focused attention on bodily sensations distressing, particularly if they are experiencing pain or anxiety.

In all cases, informed consent, patient education, and close monitoring are essential. Interventions should be adjusted to the individual’s medical status, preferences, and psychosocial context, ideally in collaboration with interdisciplinary teams [114]. Establishing safety protocols, screening tools, and clear referral pathways can enhance the responsible integration of these therapies into supportive oncology care.

Aromatherapy and the olfactory-limbic axis

Essential oils contain volatile organic compounds that, when inhaled, interact with olfactory receptors in the nasal epithelium. Unlike other sensory inputs, olfactory signals bypass the thalamus and project directly to the limbic system, specifically to the amygdala, hippocampus, and hypothalamus—regions involved in emotion regulation, memory, and autonomic control [31].

Lavandula angustifolia (Lavender): Rich in linalool and linalyl acetate (Figure 1), lavender acts via gamma-aminobutyric acid (GABA)ergic modulation, producing anxiolytic and sedative effects. Animal models show reduced spontaneous motor activity and decreased plasma corticosterone levels following inhalation [115].

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Figure 1. Chemical structures of major constituents of lavender essential oil. Linalool (A) and linalyl acetate (B) are two major constituents of lavender essential oil. Marvin JS was used for drawing, displaying, and characterizing chemical structures (RCSB PDB: Chemical Sketch). Marvin JS 17.21.0, ChemAxon (https://chemaxon.com) [116].

Citrus aurantium (Bitter orange): Contains limonene (Figure 2), which exhibits serotonergic and dopaminergic activity, associated with mood stabilization. Studies have shown a downregulation of HPA axis activity and a reduction in pro-inflammatory cytokines [e.g., interleukin-1β (IL-1β), IL-6] [117].

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Figure 2. Limonene: principal constituent of citrus essential oils. Marvin JS was used for drawing, displaying, and characterizing chemical structures (RCSB PDB: Chemical Sketch). Marvin JS 17.21.0, ChemAxon (https://chemaxon.com) [116].

Mentha piperita (Peppermint): Menthol (Figure 3) modulates TRPM8 channels, contributing to the analgesic and cooling sensations associated with this plant. It also influences cholinergic transmission, which may reduce chemotherapy-related nausea.

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Figure 3. Menthol: a major constituent of peppermint essential oil. Marvin JS was used for drawing, displaying, and characterizing chemical structures (RCSB PDB: Chemical Sketch). Marvin JS 17.21.0, ChemAxon (https://chemaxon.com) [116].

These biochemical interactions are complemented by autonomic effects, including lowered heart rate, blood pressure, and respiratory rate, which are often measurable within minutes of exposure.

Massage therapy and neuroimmune modulation

Massage stimulates cutaneous and deep pressure receptors, activating Aβ afferent fibers that inhibit nociceptive C and Aδ fibers at the spinal cord level, consistent with the gate control theory of pain [49]. Beyond pain inhibition, the stimulation of mechanoreceptors during massage fosters parasympathetic nervous system dominance. This shift is physiologically evident through decreased levels of stress-related hormones such as cortisol and norepinephrine, alongside increased secretion of oxytocin and serotonin, neurochemicals associated with relaxation, bonding, and mood regulation [118, 119]. Additionally, massage contributes to a reduction in pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and IL-6. Studies involving cancer patients have demonstrated that therapeutic massage can modulate natural killer cell activity, reduce sympathetic nervous system arousal, and improve sleep quality [120]. Together, these effects support improved homeostatic balance and bolster psychological resilience during the cancer journey [51].

Mindfulness and guided imagery: neural plasticity and gene expression

MBIs have been shown to produce measurable changes in both brain function and gene regulation. Neuroimaging studies reveal that consistent mindfulness practice leads to increased activation of the prefrontal cortex, which is associated with executive control and decision-making. Simultaneously, there is a reduction in amygdala reactivity, which helps to mitigate emotional overarousal. Enhanced connectivity between the anterior cingulate cortex and the insula has also been observed, improving interoceptive awareness and the ability to monitor internal bodily states [121]. On a molecular level, mindfulness is associated with the downregulation of nuclear factor kappa B (NF-κB) and other pro-inflammatory transcription factors, thereby contributing to decreased systemic inflammation. Additionally, mindfulness practices are associated with the upregulation of telomerase activity, which plays a role in cellular longevity, and the reduced expression of genes involved in the stress response and glucocorticoid receptor resistance. Guided imagery, a technique often used in conjunction with mindfulness, further supports these benefits by reducing hyperactivation in the limbic system and promoting the restoration of the parasympathetic nervous system. This dual impact on neural and physiological systems enhances the body’s capacity for self-regulation and stress resilience [122].

Music and art therapy: neuroaffective engagement

Music therapy activates the mesolimbic dopaminergic system, particularly the nucleus accumbens and ventral tegmental area, which are central to the brain’s reward circuitry [123]. This engagement fosters sensations of pleasure, emotional reward, and personal meaning. At the neurochemical level, music therapy has been associated with increased dopamine release, enhancing motivation and positive affect. It also modulates endogenous opioid pathways, contributing to pain relief, and leads to reduced cortisol levels, indicating a reduction in physiological stress responses [124].

In parallel, art therapy primarily engages the brain’s visual-spatial processing centers, including the occipital and parietal cortices, as well as the default mode network, which is involved in self-referential thought and introspection. Through these mechanisms, art therapy facilitates emotional expression, supports the construction of personal narratives, and encourages meaning-making during the cancer experience. Neuroimaging studies have demonstrated that expressive arts activate cognitive reappraisal pathways, which are associated with reduced anxiety and increased psychological flexibility [125].

Relaxation and sleep interventions: autonomic and hormonal shifts

Relaxation techniques such as PMR and diaphragmatic breathing shift autonomic balance toward parasympathetic dominance. This shift can be measured through various physiological markers, including lower HRV, which reflects an increase in vagal tone [126]. Additionally, these techniques lead to reduced levels of salivary cortisol and alpha-amylase—biomarkers of stress—and an increase in melatonin secretion, particularly when combined with consistent sleep hygiene practices [127]. These changes support improved sleep quality and overall well-being. CBT-I affects neural connectivity in regions associated with arousal (e.g., the insula and thalamus). It reduces catastrophic thinking about sleep, improving sleep architecture and latency over time [128]. Table 6 presents a summary that encapsulates the core mechanisms of action for each non-pharmacological intervention.

For patients: empowerment through simple, safe practices

Patients undergoing cancer treatment often experience multiple co-occurring symptoms such as pain, insomnia, anxiety, and fatigue. Engaging in supportive practices can improve symptom control and quality of life without the risks of polypharmacy.

To begin, patients are encouraged to adopt brief and manageable interventions, such as five minutes of guided breathing exercises or inhaling calming essential oils like lavender before bedtime [129]. Monitoring symptom changes through simple logs or mobile apps can help identify which strategies offer the most benefit. Creating a calming environment at home, using tools such as aromatherapy diffusers, soft background music, or soothing visual imagery, can further promote emotional and physical relaxation. Patients should also consider discussing with their healthcare team the possibility of integrating relaxation or massage therapies into their care, particularly during periods of intensive treatment such as chemotherapy or radiation [130]. When using essential oils, it is crucial to choose only clinically recommended varieties, such as Lavandula angustifolia or Citrus aurantium, and to ensure they are of high quality, pure, therapeutic grade, and appropriately diluted for safe use.

For caregivers: managing burnout and supporting healing environments

Caregivers are frequently at risk for psychological distress, sleep disruption, and physical exhaustion [4, 131]. Supporting caregivers’ well-being directly benefits patients and fosters sustainable care relationships. To promote resilience, caregivers are encouraged to incorporate daily self-care routines that may include mindfulness practices, creative art activities, or listening to calming music [132]. Engaging in these interventions alongside patients, such as participating in relaxation exercises together, can strengthen emotional bonds and create shared moments of relief. Learning simple therapeutic touch techniques, such as gentle hand massage or slow stroking, can provide comfort to both caregiver and patient while enhancing physical connection and reducing stress [55]. Guided imagery sessions, especially during waiting periods or hospital visits, offer a practical way to regulate stress responses and restore emotional balance. Additionally, caregivers may benefit from joining support groups, either in-person or online, that provide not only emotional validation but also structured coping tools that go beyond traditional verbal counseling.

For healthcare professionals: integrating non-pharmacological care into practice

Healthcare professionals play a crucial role in identifying suitable interventions, ensuring patient safety, and promoting consistent use. Though these practices are often termed “complementary”, they are increasingly recognized as part of whole-person, integrative oncology care.

To support their effective use, clinicians should routinely screen patients for symptoms such as anxiety, insomnia, and fatigue using validated assessment tools. Recommendations should be tailored to the patient’s needs, preferences, and care setting. For example, guided imagery may be beneficial for managing procedural anxiety, while CBT-I is suitable for addressing persistent sleep disturbances. When possible, professionals should provide or refer patients to structured programs such as MBSR, music therapy, or massage services available in oncology centers [90, 132].

Ensuring that these interventions are delivered safely requires that therapists are appropriately trained and credentialed. Licensed massage therapists, certified aromatherapists, and mindfulness instructors with experience in clinical settings should be involved in patient care. In addition, healthcare providers have a responsibility to educate interdisciplinary teams on the mechanisms, evidence base, and benefits of these approaches, fostering a collaborative and unified model of integrative care [133].

Importantly, equity in access must be prioritized. Non-pharmacological interventions should be available to all individuals, regardless of socioeconomic status, literacy level, or geographic location. The development of culturally adapted materials and the use of community-based resources—such as audio guides in native languages—can help extend the reach and impact of these supportive practices, ensuring inclusivity in cancer care delivery [134, 135].

Real-world implementation challenges

Practical and structural barriers often constrain the successful integration of non-pharmacological therapies in oncology. A central challenge is the lack of adequately trained personnel equipped to deliver these interventions safely in cancer settings [136]. Oncology nurses, psycho-oncologists, massage therapists, and integrative health providers may lack access to standardized training in modalities such as aromatherapy, mindfulness, or sleep education [137]. While some institutions offer in-house workshops or continuing education, there is no universal credentialing pathway for many of these interventions, leading to variability in quality and safety. Additionally, interdisciplinary teams may be unaware of referral processes or hesitant to recommend non-pharmacological approaches due to uncertainty about the strength of evidence or institutional guidelines [138].

The absence of structured protocols and documentation systems further complicates the clinical integration process. Supportive therapies are rarely tracked in electronic health records (EHRs), making it difficult to measure outcomes, communicate across teams, or justify resource allocation [139]. Embedding symptom screening tools and patient-reported outcome measures (PROMs) into routine oncology workflows can help identify candidates for non-pharmacological support and track the efficacy of interventions over time [140]. Finally, real-world implementation requires institutional buy-in and administrative support. This includes allocating time for staff training, budgeting for therapy supplies (e.g., essential oils, music devices), and recognizing these interventions as integral—not optional—components of holistic cancer care.

Access, equity, and digital solutions

Equitable access to non-pharmacological interventions remains a significant challenge, particularly for patients in rural, low-income, or underserved communities. Many of these supportive therapies—such as massage, art therapy, and mindfulness training—are more readily available in academic or urban cancer centers [141]. At the same time, patients in community settings may have limited or no access. Additionally, cultural, linguistic, and literacy barriers can hinder patient engagement, especially when educational materials or therapeutic instructions are not adapted to diverse populations [142]. Addressing these disparities requires intentional efforts to develop inclusive models of care that account for differences in language, culture, socioeconomic status, and healthcare infrastructure.

Digital tools have emerged as promising avenues to overcome geographic and resource-based barriers. Mobile applications and web-based platforms now offer guided mindfulness, progressive relaxation, sleep hygiene programs, and even digital CBT-I, often at low or no cost [69]. These tools can extend the reach of care into the home environment, providing continuous support between clinical visits. For example, digital programs such as Sleepio, Headspace, and Insight Timer have demonstrated usability and clinical impact in oncology populations, particularly when supplemented with brief clinician guidance [143–145]. However, digital inclusion must be prioritized: interventions must be user-friendly, available in multiple languages, and compatible with varying levels of digital literacy. Partnerships with community organizations and patient advocacy groups can help promote uptake and ensure that technology-enhanced interventions are not limited to tech-savvy or high-resource users.

Equity-focused implementation also benefits from training lay caregivers and community health workers in basic supportive techniques, such as hand massage or guided breathing, thereby extending care beyond formal clinical teams [146]. Integrating these approaches into community clinics, hospices, and primary care settings provides a pathway toward more inclusive and scalable models of integrative oncology care.

Cost-benefit considerations

While non-pharmacological interventions are often perceived as ancillary, emerging evidence suggests that they may offer significant economic benefits by improving symptom control, reducing reliance on medications, and enhancing the well-being of both patients and caregivers. Many of these strategies—such as aromatherapy, sleep hygiene education, guided imagery, and caregiver-led massage—are low-cost, low-risk, and relatively easy to implement, particularly when adapted for home use or delivered via digital platforms. By reducing symptom burden (e.g., anxiety, nausea, insomnia), they may help decrease the need for sedatives, antiemetics, or anxiolytics, which in turn could lower polypharmacy-related adverse events and healthcare utilization [147].

Preliminary studies indicate that integrative oncology programs incorporating non-pharmacological therapies can reduce hospital admissions, emergency department visits, and length of stay, particularly when used proactively during active treatment or in survivorship care plans [148, 149]. Furthermore, interventions that improve sleep and emotional resilience may enhance treatment adherence and reduce caregiver burnout, contributing to indirect savings for health systems and communities.

Despite these potential benefits, rigorous cost-effectiveness analyses remain limited. Most studies focus on clinical outcomes such as pain or mood, with few capturing long-term economic data or system-wide impact. Health economic evaluations should be prioritized in future research, particularly to assess whether investments in staff training, digital tools, or therapy infrastructure yield measurable returns in quality-adjusted life years (QALYs), caregiver productivity, or healthcare cost avoidance [150, 151]. Demonstrating financial value is especially important for informing reimbursement models, policymaking, and institutional resource allocation, factors that are critical for the sustainable integration of these approaches into standard cancer care.

Research and policy recommendations

To ensure that non-pharmacological interventions are sustainably integrated into cancer care, future research must focus on expanding the evidence base, standardizing delivery protocols, and informing supportive policy frameworks. Although existing studies support the clinical effectiveness of interventions such as mindfulness, massage, and aromatherapy, further high-quality RCTs are needed to clarify optimal dosing, delivery formats, and long-term effects across diverse cancer populations. Standardizing protocols, such as session duration for guided imagery or recommended dilution for essential oils, would enhance consistency, reproducibility, and safety across settings.

In parallel, research must prioritize inclusion. Populations such as pediatric, geriatric, rural, and ethnically diverse patients are often underrepresented in many trials, which limits the generalizability of the findings. Culturally tailored interventions, multilingual educational materials, and participatory research approaches are essential for ensuring that future models of care reflect the needs and realities of all patients and caregivers [152].

At the policy level, professional societies and regulatory bodies should collaborate to develop certification standards and best-practice guidelines for non-pharmacological therapies in oncology. These should outline minimum competencies for practitioners, safety criteria, and evidence thresholds for clinical recommendations. Additionally, health insurers and public health systems should consider revising reimbursement frameworks to support interventions that demonstrably improve quality of life, reduce medication use, and lower healthcare costs.

Ultimately, institutional policies must acknowledge the legitimacy and value of supportive care by integrating non-pharmacological interventions into care pathways, EHRs, and interdisciplinary team workflows. Clear referral mechanisms, informed consent procedures, and documentation practices can further support their routine use and alignment with ethical and professional standards. In combination, these research and policy efforts will be essential to moving non-pharmacological strategies from the margins to the mainstream of comprehensive cancer care. These research and policy priorities align with the current evidence landscape summarized in Table 7, where specific modalities, such as art and music therapy, are still classified as ‘promising but inconclusive’ due to variability in outcome measures and limited standardization of these approaches. Clarifying these gaps through coordinated research and guideline development will be essential to strengthening their clinical recommendation status.

To support clinical decision-making and reflect the variability in the current literature, Table 8 summarizes the strength of evidence for each intervention based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence (2022) [153]. This framework categorizes the quality of evidence from Level 1 (highest) to Level 5 (expert opinion or case series), providing a structured approach to evaluating the robustness of available data. Table 8 also highlights common clinical indications and key research gaps.