Feasibility of Adjunctive BLT for Amelioration of Fatigue in Chinese Cancer Patients Admitted to a Palliative Care Unit

Fatigue is the most common symptom in palliative care patients who have advanced cancer. Fatigue is also one of the most underreported hence under-treated symptoms. Patients may perceive it as a condition to be endured, whereas healthcare workers find it very challenging to assess and treat due to its subjective nature and multi-dimensional causes.

However, evidence-based practice to tackle this distressing problem is still inadequate, and that a one-size fit all approach is unrealistic. Various pharmacological options have been examined, but due to limited evidence, no specific drug could be recommended.

Latest development in management of fatigue includes non-pharmacological approach. Bright Light Treatment (BLT) has also evolved as a favourable treatment for cancer-related fatigue. BLT is the prescription of artificial bright light over a designated period of time. Recent clinical evidence showed that BLT reduced symptom of fatigue in patients undergoing active chemotherapy and cancer survivours.

There is however no data on bright light therapy used in in-patient palliative care settings.

A single group, prospective interventional study will be conducted in in-patient palliative care unit of Shatin Hospital (N = 42). The aim is to assess the feasibility and impact of BLT as an in-patient intervention in a cohort of local Chinese palliative care in-patients diagnosed with incurable cancer with documented symptom of fatigue, and to ascertain the changes of fatigue, mood, sleep and quality of life after 1-week exposure of BLT.

Fatigue is the most common symptom in palliative care patients who have advanced cancer, ranging from 59% to 77% depends on the assessment method (1). There is limited local data on the prevalence of fatigue in cancer patients. A cross-sectional study by Dr KY Lam in 2009 (unpublished data) found 53% of 55 patients receiving palliative care suffered from severe fatigue. A cross-sectional symptom screening of all the patients in the palliative care ward in Shatin Hospital showed 22 out of 55 (40%) patients reported fatigue (unpublished data).

The fatigue experienced by cancer patients is multi-dimensional. The feeling may be a physical sensation (weakness, tiredness, exhaustion, unable to perform tasks), an affective sensation (low mood, lack of motivation), or a cognitive sensation (lack of concentration, difficulty thinking clearly). This phenomenon is also subject to cultural interpretation therefore there is a need to understand each subject's perception and experience of fatigue within his or her own cultural context (2, 3).

Fatigue is also one of the most under-reported hence under-treated symptoms. Patients may perceive it as a condition to be endured, whereas healthcare workers find it very challenging to assess and treat due to its subjective nature and multidimensional causes. The impairment in self-care capabilities and daily functioning lead to negative effects on desire to continue treatment thus affecting the functional recovery even in patients with a more stable disease status (3-5). The quality of life (QOL) of patients, which is our focus in palliative care service, is heavily reduced (6).

However, evidence-based practice to tackle this distressing problem is still inadequate, and that a one-size fit all approach is unrealistic (7). Various pharmacological options have been examined, but due to limited evidence, no specific drug could be recommended for the treatment of fatigue in palliative care patients in the latest Cochrane review in 2015 (8).

Latest development in management of fatigue includes non-pharmacological approach. Effect size in reducing fatigue in various treatments were summarised in a report by Bower (9). Exercise was more effective than control in reducing fatigue with a mean effect size of -0.27. Psychosocial intervention trials that included fatigue as a primary or secondary outcome have shown reductions in fatigue relative to control, with effective sizes ranging from -0.10 to -0.31. Psychostimulant trials, most of which were conducted among patients with advanced disease and used methylphenidate, suggested that psychostimulants were more effective than placebo in improving fatigue with an effect size of -0.28. Of note, two studies with larger sample size showed no benefit for methylphenidate vs. placebo for improving fatigue (10, 11). The application of non-pharmacological approach in our local patients was even more limited. A pilot study of 26 patients receiving palliative care in Shatin Hospital showed a mean change score of 0.5 (1.862) of improvement in Brief Fatigue Inventory (BFI) Q3 after two weeks of in-patient multidisciplinary care (unpublished data). The estimated effect size of the pilot study was 0.268 (mean change/SD = 0.5/1.863). Overall, these data suggest that non-pharmacological treatments (e.g. exercise, psychoeducation, support program, cognitive-behavioural therapy) have a mild to moderate effect on improving symptom of fatigue.

Over these few decades, Bright Light Treatment (BLT) has also evolved as a favourable treatment for cancer-related fatigue. BLT is the prescription of artificial bright light over a designated period of time. It was initially developed for the treatment of seasonal affective disorder, and found to be as effective as antidepressants for treatment of depressive symptoms during winter (12). The National Comprehensive Cancer Network (NCCN) guidelines on cancer-related fatigue (13) and a recent review on all treatment options of cancer-related fatigue (14) suggested that BLT is a safe and accessible option.

There are several mechanisms on how light therapy works. Firstly, it works through improving alertness. Healthy subjects who had increasing bright light exposure as compared to dim light would have a rapid effect of decrease in sleepiness and improvement in their performance (15). Secondly, BLT works through improving mood. Efficacy of BLT have been demonstrated in seasonal affective disorder (12), non-seasonal depression (16) and bipolar depression (17). Thirdly, BLT works through regulation of circadian rhythm. Circadian disruptions were demonstrated in 55 community-dwelling cancer patients receiving palliative care (18). Although the cause and effect between exacerbated fatigue and decreased light exposure could not be confirmed, increased fatigue was significantly correlated with decreased light exposure among patients with breast cancer (19). Exposure to bright light in the morning leads to an advance of endogenous circadian rhythms that results in a realignment of these rhythms with the individual's sleep-wake cycle. Therefore, possibly by providing a corrective phase advance with morning BLT, rhythm dysregulation could be corrected resulting in a reduction of fatigue symptom.

Two trials investigated the impact of light therapy on fatigue and QOL in the same group of 39 women with breast cancer undergoing active chemotherapy (20, 21). Results suggest that morning bright light treatment helped prevent the typical worsening of fatigue and quality of life during chemotherapy treatment. Although the light treatment did not improve overall fatigue in this sample, the lack of deterioration in total fatigue during a period where symptoms typically worsen was encouraging. Another study sought to determine the effect of bright light treatment on cancer-related fatigue among 36 post-treatment survivors (22). At the end of the treatment period, patients who had received bright white light therapy were no longer clinically fatigued, whereas 55% of the patients in the active control condition continued to report clinical fatigue. The effects of the bright white light treatment were maintained 3-weeks post-intervention.

A more recent study again focused on cancer survivors (23, 24). The total fatigue score using the Multidimensional Fatigue Symptom Inventory-Short Form showed an effect size of 1.20 in the bright-white-light intervention group and an effect size of 0.93 in the supposing placebo arm dim-red-light group. These were large within group effect size. This study employed BLT as an adjunctive therapy and the participants were not excluded for using their usual medications (including psychotropic medications). A randomised controlled trial in 2007 reported that selective serotonin reuptake inhibitor (SSRI) do not appear to have beneficial effects on cancer-related fatigue, supporting the distinction between fatigue and depression in cancer patients and suggesting that fatigue is not solely a symptom of depression (25).

Bruera and team tried to introduce BLT to patients with advanced cancer and insomnia in out-patient settings (26). One shortcoming of their study was partly due to a high attrition rate especially in the control arm where dim red light was used as placebo. They suggested future studies to incorporate alternative trial designs to improve the adherence.

There is however no data on bright light therapy used in in-patient palliative care settings. Conducting research on patients receiving palliative care has been particularly challenging (27, 28). Barriers include the difficulty in participation due to limitations of serious illness, complex symptoms and clinical instability, resulting in high attrition and missing data. The MOREcare Statement (29) suggested researchers to use measures which are as short and simple as possible.

Despite these limitations, the present evidence suggests that BLT, a safe and easily delivered treatment, may be a clinically feasible and effective intervention to reduce symptom of fatigue in cancer palliative care patients during hospital stay. This study aims to test the feasibility of administering bright light therapy in cancer palliative care patients for the treatment of fatigue.

Eligibility Criteria:
Inclusion Criteria:

* Adult patient aged 18 years old or above
* Chinese ethnic group
* Diagnosis of incurable cancer
* A score of \>=3 in Brief Fatigue Inventory after a period of standard care

Exclusion Criteria:

* Patients who are imminently dying
* Patients who are undergoing chemotherapy or radiotherapy
* Patients who have history of epilepsy, brain tumour, brain metastasis
* Patients who are blind or have retinal disease
* Patents who have photosensitive skin condition
* Patients who have history of bipolar disorder as BLT has been suggested to increase the risk of manic swing in patients with bipolar disorder
* Patients who have their dosage of antidepressants adjusted within 6 weeks
* Patients who have difficulties to communicate effectively
* Patients with impaired mental status precluding the completion of the questionnaire (AMT \<5)
* Patients who are unable to give valid consent