diff --git "a/test/parse_examples/PMC11102686.xml" "b/test/parse_examples/PMC11102686.xml" new file mode 100644--- /dev/null +++ "b/test/parse_examples/PMC11102686.xml" @@ -0,0 +1,3564 @@ + + + +
+ + + pmc + + + + Integr Cancer Ther + Integr Cancer Ther + ICT + spict + + Integrative Cancer Therapies + + 1534-7354 + 1552-695X + + SAGE Publications + Sage CA: Los Angeles, CA + + + + 38757745 + 11102686 + 10.1177/15347354241252698 + 10.1177_15347354241252698 + + + Study Protocol + + + + Exploring Guolin Qigong (Mind-Body Exercise) for Improving Cancer Related + Fatigue in Cancer Survivors: A Mixed Method Randomized Controlled Trial Protocol + + + + + https://orcid.org/0000-0001-6296-6052 + + Low + Sara L. K. + + MRes + 1 + + + + Ho + Gwo Fuang + + FRANZCR + 2 + + + + Liu + Bingkai + + PhD + 3 + + + + Koh + Eng-Siew + + FRANZCR + 4 + + + + Fei + Yutong + + PhD + 5 + + + + https://orcid.org/0000-0003-1071-443X + + Teo + Chiah Shean + + MD + 6 + + + + https://orcid.org/0000-0002-2909-5926 + + Zhu + Xiaoshu + + PhD + 1 + + + + Western Sydney University, Penrith South, + NSW, Australia + University Malaya Medical Centre, Kuala + Lumpur, Wilayah Persekutuan, Malaysia + Pitié-Salpêtrière Hospital, + Paris, France + University of New South Wales, Liverpool, + NSW, Australia + Beijing University of Chinese Medicine, + Beijing, China + UCSI University, Malaysia + + Xiaoshu Zhu, Chinese Medicine Centre (an + international collaboration between Western Sydney University and Beijing University of + Chinese Medicine), Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, + Australia. Email: x.zhu@westernsydney.edu.au + + + 17 + 5 + 2024 + + + 2024 + + 23 + 15347354241252698 + + + 5 + 8 + 2023 + + + 5 + 4 + 2024 + + + 18 + 4 + 2024 + + + + © The Author(s) 2024 + 2024 + SAGE Publications Inc unless otherwise noted. + Manuscript content on this site is licensed under Creative Commons Licenses + + + https://creativecommons.org/licenses/by/4.0/ + This article is distributed under the terms of the Creative Commons + Attribution 4.0 License ( + https://creativecommons.org/licenses/by/4.0/) which permits any use, + reproduction and distribution of the work without further permission provided the + original work is attributed as specified on the SAGE and Open Access page ( + https://us.sagepub.com/en-us/nam/open-access-at-sage). + + + + + Background: +

Cancer-related fatigue and its associated symptoms of sleep disorder and depression + are prevalent in cancer survivors especially among breast, lung, and colorectal cancer + survivors. While there is no gold standard for treating cancer-related fatigue + currently, studies of mind-body exercises such as Qigong have reported promise in + reducing symptoms. This study was designed to evaluate the feasibility and effect of + Guolin Qigong on cancer-related fatigue and other symptoms in breast, lung and + colorectal cancer survivors while exploring their perceptions and experiences of + Guolin Qigong intervention.

+ + + Methods: +

This is an open-label randomized controlled trial with 60 participants divided into 2 + study groups in a 1:1 ratio. The intervention group will receive 12 weeks of + Guolin Qigong intervention with a 4-week follow-up while control will receive usual + care under waitlist. The primary outcome will be feasibility measured based on + recruitment and retention rates, class attendance, home practice adherence, nature, + and quantum of missing data as well as safety. The secondary subjective outcomes of + fatigue, sleep quality and depression will be measured at Week-1 (baseline), Week-6 + (mid-intervention), Week-12 (post-intervention), and Week-16 (4 weeks + post-intervention) while an objective 24-hour urine cortisol will be measured at + Week-1 (baseline) and Week-12 (post-intervention). We will conduct a semi-structured + interview individually with participants within 3 months after Week-16 + (4 weeks post-intervention) to obtain a more comprehensive view of practice + adherence.

+ + + Discussion: +

This is the first mixed-method study to investigate the feasibility and effect of + Guolin Qigong on breast, lung, and colorectal cancer survivors to provide a + comprehensive understanding of Guolin Qigong’s intervention impact and + participants’ perspectives. The interdisciplinary collaboration between Western + Medicine and Chinese Medicine expertise of this study ensures robust study design, + enhanced participant care, rigorous data analysis, and meaningful interpretation of + results. This innovative research contributes to the field of oncology and may guide + future evidence-based mind-body interventions to improve cancer survivorship.

+ + + Trial registration: +

This study has been registered with ANZCTR (ACTRN12622000688785p), was approved by + Medical Research Ethic Committee of University Malaya Medical Centre (MREC ID NO: + 2022323-11092) and recognized by Western Sydney University Human Research Ethics + Committee (RH15124).

+ + + + Qigong + cancer + cancer survivors + fatigue + sleep + insomnia + depression + cortisol + mind body exercise + + + + + + Chinese Medicine Centre + + + + Research Fund + + + + + Western Sydney University + https://doi.org/10.13039/501100018822 + + + Research Training Program Fund + + + + + cover-date + January-December 2024 + + + typesetter + ts1 + + + + + + + Background +

Cancer-related fatigue (CRF) has been increasingly recognized as an important symptom + during and after treatment of cancer, impacting physical, mental, and emotional functions. + 1 + CRF is a + prevalent symptom among survivors of the most common types of cancer, including breast, + lung, and colon cancer.2,3 It is a distressing + symptom + 3 + and one of + the main reasons for the interruption of treatment or exacerbation of the disease. + 2 + Between 74% + and 90% of cancer survivors undergoing chemotherapy or radiotherapy4 +-6 experienced fatigue with adverse effect on other + co-morbidity, quality of life, independent living, and work productivity.3,7 While fatigue is more + prevalent within 6 months of receiving cancer treatment, cancer survivors including + those who did not receive treatment continue to experience fatigue many years after + treatment. + 5 +

+

Cancer diagnosis and its treatment also bring with it a host of physiological changes + affecting various functions of the body including cortisol dysregulation associated with + fatigue,8 +-12 sleep disorders,8,13 +-15 depression,12,16 + anxiety, stress,17,18 functional disability, + 12 + survival + outcomes, and prognosis13 + ,18 +-21 + in cancer survivors.

+

The pathogenesis of CRF is still unclear, but might include proinflammatory cytokines, + growth factors, circadian rhythm modulation, adrenal axis interruption, serotonin + imbalance, afferent activation of the vagus nerve, and the production or use of abnormal + adenosine triphosphate. + 22 + Host + factors not related to cancer and its treatment such as genetic, biological, psychosocial, + and behavioral factor also play an important role in the development of CRF. + 23 +

+

CRF is also associated with various risk factors such as low performance status, + undergoing chemoradiotherapy, insomnia, pain, neuroticism, depression and being female. + 24 +

+

It is further suggested that cancer-related fatigue is a composite of interacting + responses to stress related to diagnosis and treatment, with the relationship of sleep + disorders, depression, anemia, and inflammation featuring centrally for those under + treatment as well as into the survivorship phase. + 25 + CRF and a + number of these factors and symptoms, including sleep disruption and emotional distress + often co-occur as a symptom cluster,26 +-28 with some of these + associations potentially linked to the underlying inflammatory biomarker changes such as + cortisol level + 29 + most + associated with fatigue.3,24,30

+

Exploring symptom clusters is an important gap in symptom research to shed light on the + common biological mechanisms + 31 + and is + gaining increased attention in the field of oncology in an attempt to improve the quality + of life of patients diagnosed with cancer. + 32 +

+

Hence, there is a need to pay attention to the co-occurrences of fatigue, sleep disorder + and depression as a symptom cluster in the evaluation and treatment of cancer survivors + experiencing CRF.3,26 +-28

+

In spite of fatigue being the most common symptom reported by patients, they were least + likely to report getting wanted help for it, perhaps due to the complexity of treating + this common condition. + 5 + Given the + multifactorial nature of CRF which is still poorly understood, there is currently no + “gold standard” treatment for CRF despite some approaches such as exercise, + psychosocial interventions, and mind-body interventions being reported to yield beneficial + effects in improving CRF. + 23 +

+

Emerging studies have shown that mind-body exercise such as Qigong can reduce fatigue, + improve sleep, depression, anxiety, quality of life and cognitive changes associated with + cancer as well as biomarkers of stress, cortisol level, inflammation and immune function + in cancer survivors during and after treatment.29,33 +-44

+

The term “Qigong” is made up of 2 characters: Qi and Gong translated as the + skill or practice to cultivate Qi. The concept of Qi, an inherent function and energizing + essence of human being, is found in Traditional Chinese Medicine. + 45 + Qi also + refers to life force, vitality, or intelligence within a bio-electric body46,47 as well as the + universe. + 48 + There are + a few thousand different forms of Qigong such as Tai Chi, BaDuanJin, Chan Chuang, Zhineng + Qigong, and Guolin Qigong, all of which can be broadly classified into Chinese Medical + Qigong, Daoist Qigong, Buddhist Qigong, Confucian Qigong, and martial arts Qigong. All + forms of Qigong involve the recognition and cultivation of Qi to promote a balanced Qi and + smooth flow of Qi in the body + 49 + to + enhance physical, psychological, and spiritual health through mind-body integration of + specific movements, breathing techniques, and meditation. + 50 + Mind-body + integration of Qigong is also believed to promote health through the activation of + neurohormonal pathways and other physiological mechanisms. + 51 + Qigong + offers several potential advantages when compared to modern medical therapy as it + emphasizes a holistic approach with minimal adverse effects40,52 when practiced + correctly after proper guidance. It is also known to improve neuropsychiatric conditions + 53 + without + the side effects of pharmaceutical drugs. More importantly, it promotes self-empowerment + as it empowers individuals to take an active role in their health. Lastly, Qigong is more + cost- effective compared to certain medical treatments as once learned, it can be + practiced regularly to promote a healthy lifestyle without the need to incur additional + expenses.

+

Among the many styles of Qigong is Guolin Qigong (GQ). This form of Qigong has been + specifically adapted for cancer survivors by offering a moderate and adaptable exercise + routine. It is a moderate walking exercise that integrates coordinated arm movements and + trunk rotations, coupled with controlled breathing techniques. What sets it apart is its + gentle nature, designed to be accommodating and adjustable. This adaptability is crucial, + as it allows for modifications in speed, duration, and intensity, ensuring that it caters + to the unique health conditions and needs of individual cancer survivors. The flexible + approach of GQ prioritizes the well-being and comfort of each participant, making it a + safe and beneficial practice for those navigating the complexities of cancer recovery. + Therefore GQ is suitable for cancer survivors—especially advanced cancer patients + who may be unable to engage in other forms of physical activity. + 54 + A + moderate-intensity walking exercise program was reported to be a feasible and effective + intervention method for managing fatigue,55,56 + anxiety, depression, + 57 + and sleep + in cancer survivors at different stages of cancer.58 +-60 GQ exercise training also facilitates the inhaling of + oxygen which is important for the homeostasis of oxygen-carbon dioxide in controlling + cancer and ultimately survival, as supported by a 10-year longitudinal cohort study of 122 + lung and nasopharyngeal cancer patients which reported that improvements in End Tidal + Breath Holding Time (ETBHT), alveolar O2 (aO2) pressure, and + alveolar CO2 (aCO2) pressure capacity with GQ was associated with + higher survival years, 5 years survival rate and survival probability. + 61 + In the + above-mentioned cohort study, + 61 + GQ also + demonstrated improvement in depression among cancer participants. Additionally, in breast + cancer patients undergoing 5 to 6 weeks of radiotherapy, women with elevated + depressive symptoms at the start of treatment showed significant enhancements in fatigue + and QOL. + 50 +

+

However, the impact of GQ on CRF, often associated with sleep and depression3,26 +-28 and its correlation with cortisol levels has not been + explored.

+

In addition to that, a qualitative study to evaluate the perception and acceptance of GQ + is needed to explore the feasibility, adherence, and experience related to this complex + intervention. It aims to understand the more subjective domains and identify potential + factors for improving healthcare + 62 + to + address the multi-faceted needs of this population. Such research, however, has not been + conducted yet.

+

Therefore, the purpose of this paper is to describe the protocol of a mixed-method study + comprising,

+ + +

A randomized-controlled trial to evaluate the feasibility of GQ training and its + effect on CRF, sleep, depression, and cortisol levels in breast, lung and colon cancer + survivors and,

+ + +

Semi-structured interview with study participants from the randomized- controlled + trial to understand their perceptions and experiences of GQ to identify: + +

(a) other physiological and psychological benefits gained from the GQ + intervention,

+ + +

(b) the barriers to GQ participation, adherence, and recommendations for + improvement.

+ +

+ + +

We hypothesized that

+ + +

It is feasible for cancer survivor participants to engage in the GQ training and + those who participated in the GQ training will experience positive impacts on CRF, + sleep, depression, and cortisol level. Feasibility of this study is established at + about 80% to 85% retention rate and 75% to 85% class attendance rate based on prior + similar studies.63 +-65

+ + +

The semi-structured interview will identify a broader spectrum of benefits and + barriers to participation and adherence to GQ training to provide valuable insights + for program enhancement.

+ + + + + Methods + + Study Design + + Intervention/clinical trial +

The primary objective of this study is to explore the feasibility of a GQ + intervention in patients with various cancer types who experience CRF. This study + includes the 3 most prevalent cancer types that is, breast, lung and colon cancers. + This is a randomized-controlled trial that compares the GQ intervention group to a + usual care waitlist control group receiving standard medical care allocated in a 1:1 + ratio to evaluate the feasibility and effects of a 12-week GQ intervention on 60 + eligible breast, lung, and colorectal cancer survivors’ fatigue, sleep quality, + depression, and 24-hour urine cortisol change. Refer to Figure 1 for an overview of the + study. This study protocol was developed based on the SPIRIT 2013 Statement (Standard + Protocol Items: Recommendations for Interventional Trials) (Supplemental Material 1). + 66 +

+ + + +

Participant flow diagram.

+ + + + + + Interview +

We will use a qualitative descriptive design, with a semi-structured interview to + collect in-depth information to enhance our understanding of the perceptions and + experiences of GQ participation of cancer survivors based on purposive sampling until + data saturation is reached.

+

The qualitative interview will be reported within the primary randomized feasibility + trial according to the guidelines recommended in the CONSORT 2010 statement extension. + 67 +

+ + + + Study Setting +

The trial is conducted at University Malaya Medical Centre (UMMC) in Kuala Lumpur, + Malaysia. Participants are recruited by referrals from UMMC or online and print + advertisements such as posting recruitment in UMMC, cancer support groups, GQ + Association and GQ practice stations around Klang Valley, and social media platforms + including X Corp (formerly known as Twitter) and Facebook.

+ + + Recruitment +

Recruitment started in October 2022. Upon first contact, the Researcher will screen + potential breast, lung, or colon cancer survivors and provide information about the + study to those who meet the eligibility criteria and indicate interest to participate. + Thereafter a Physician/Oncologist Screening Form, Participant Information Sheet, and 2 + copies of Participant Consent Form will be given, explained, and a separate date agreed + for in-person enrollment. + 67 +

+ + + Inclusion Criteria + + +

(1) Age ≥ 18 years old;

+ + +

(2) *Cancer survivor diagnosed with breast, lung and colorectal cancer;

+ + +

(3) Able to read and answer questionnaires in English and/or Bahasa Malaysia + language by oneself;

+ + +

(4) Suffering from moderate to severe fatigue as assessed by the simple + fatigue scale; with severity score of 3 and above + 68 + + ;

+ + +

(5) Able to use smart phones and the WeChat or WhatsApp application;

+ + +

(6) Life expectancy of more than 3 months;

+ + +

(7) Able to give informed consent;

+ + +

(8) Available and willing to comply with the study requirements.

+ + +

*A cancer survivor is defined as an individual diagnosed with cancer through the + balance of life according to National Cancer Institute. + 69 +

+

Including cancer survivors throughout the continuum of survivorship in our sample + inclusion criteria allows us to capture a comprehensive spectrum of experiences. From + those newly diagnosed to long-term survivors, each stage brings unique perspectives on + GQ participation and its impact. This approach ensures a thorough exploration of how GQ + intervention intersects with varying phases of the cancer journey, providing a rich + understanding of the diverse narratives and challenges encountered across this + continuum.

+ + + Exclusion Criteria + + +

(1) Cardiopulmonary disease, nerve, muscle, or joint disease, or other + malignant tumors affecting movement;

+ + +

(2) Mental illness or serious cognitive impairment and defects in language + that significantly impairs communication;

+ + +

(3) Post-operative heart, cerebral vessel, or other serious complications;

+ + +

(4) Neurological degenerative disease (e.g. dementia), reduced cognitive; + capacity in any way that would affect ability to understand trial procedures and + give informed consent;

+ + +

(5) Patients who are not able to walk;

+ + +

(6) Other medical conditions which would preclude study intervention or make + study participation unsafe such as severe chronic heart failure.

+ + + + + Randomization and Blinding +

After informed consent, participants will be randomly assigned to either the GQ or + usual care waitlist control group at a 1:1 ratio with the random sequence generated by + an online computerized randomization system using minimization method70 +-72 by an independent + research assistant.

+ + + Intervention +

After being advised of group allocation, the study participant will be given a few days + to decide on whether to proceed with enrollment. Incorporating a brief period for + participants to reflect and opt-out after randomization supports ethical research + practices, ensures ethical informed consent, reduces pressure, enhances retention, and + respects participant autonomy in clinical trials or studies.

+ + Guolin Qigong +

Participants in the intervention group will attend a 2-hour supervised face-to-face + (F2F) GQ training class for 12 weeks with home-practice on non-class days. + There will be 2 training classes per week for the first 2 weeks and once per + week for the next 10 weeks.

+

The GQ training involves a modified version of a Chinese medical qigong therapy often + referred to as “walking qigong” developed by Guo Lin. + 38 + + GQ was developed specifically for cancer and consisted of several breathing and moving + exercises. The GQ training in the current study includes the following 3 main + exercises:

+ + +

1. Feng Hu Xi Zhi Ran Xing Gong (Natural Wind Breathing Walking)

+ + +

Participants walk in a circle, synchronizing their breathing, arm movements, and + steps focusing on the movement of their body with the goal of calming one’s + mind, relaxing various parts of the body and the mind, and revitalizing the + “life-force,” that is, qi.

+ + +

2. Dian Bu Gong (Step Tap Method)

+ + +

A modified natural Wind Breathing Walking Exercise with additional step tap.

+ + +

3. Sheng Jiang Kai He Fa (Ascending, Descending, Opening, and Closing + Method)

+ + +

A calming and relaxation method of synchronized arms and legs movements on the spot + which can be practiced within limited space.

+

Each main exercise has to be practiced separately as individual sets comprising 3 + parts:

+ + +

a. Preparatory relaxation exercise (gentle breathing and meditation; + 4 minutes):

+ + +

In relaxed standing posture, synchronize the breath with gentle arm movements in + front of the abdomen (opening and closing of the Dantian). Dantian is a Chinese + medicine concept that refers to the “elixir field” or “energy + center.” It has different locations but often referred to the lower abdomen + between the navel and pubic bone of the human body.73,74

+ + +

b. Main exercise

+ + +

i. Feng Hu Xi Zhi Ran Xing Gong (Natural Wind Breathing Walking) or

+ + +

ii. Dian Bu Gong (Step Tap Method) or

+ + +

iii. Sheng Jiang Kai He Fa (Ascending, Descending, Opening, and Closing + Method).

+ + +

c. Concluding exercise: breathing exercises, opening, and closing of the + Dantian, and self-massage (3-6 minutes). + 50 +

+ + +

Please refer to Supplemental Material 2 for detailed steps. All + movements will include modifications to enhance safety. Participants will be advised + to rest as and when necessary, according to their health status.

+

The F2F GQ class will be taught by qualified GQ instructors who are both long-term + cancer survivors with more than 20 years of GQ training experience to ensure + the full potential of the GQ intervention. The Researcher, who is a registered Chinese + Medicine practitioner in Malaysia and Australia with more than 20 years’ + experience in Qigong, will be in attendance during the F2F GQ class to ensure the safe + and seamless facilitation of the training session.

+

Home practice is recommended for non-class days according to individual health status + and available time. + 54 + + Participants will be provided with class notes and video links (Supplemental Material 3) to promote and support home + practice. Home practice after the intervention period is encouraged for incorporation + into daily life to foster a healthy lifestyle.

+ + + + Usual Care Waitlist Control +

Participants in the usual care waitlist control group will be advised to continue with + their usual care routines and exercises and will be asked not to attend any other Qigong + exercises. They will be offered to attend the same GQ training class after Week-16 of + the GQ training of their cohort.

+

However, to maintain integrity of the study, instructors will not be informed about the + allocation of participants. Consequently, when instructors commence training of + subsequent cohorts, they will be unaware of which participants belong to the + intervention group (commencing from Week 1), and which are part of the control group + (joining the GQ group in Week 1), given the GQ training will be offered continuously. + This ensures the instructors are effectively blinded to the allocation to maintain + impartiality in the delivery of the training and minimizes any potential biases that may + arise from instructor knowledge of group allocation.

+ + + Study Assessments +

The variables under consideration will encompass basic demographic data, primary + outcomes, and secondary outcomes. Basic characteristics will be collected at baseline + (Week-1).

+

Primary feasibility outcomes on adherence, attendance, and any adverse events will be + recorded throughout the intervention period from Week-1 to Week-12 in the practice diary + by the participants. Secondary patient-reported outcomes on fatigue, depression, and + sleep will be measured at baseline (Week-1), mid-intervention (Week-6), + post-intervention (Week-12), and 4 weeks after completion of intervention + (Week-16). Urine samples (for urine cortisol test) to assess 24-hour urinary cortisol + will be collected a day prior to enrollment date and post-intervention (Week-12). + Primary feasibility outcomes and secondary patient-reported outcomes will be assessed by + an independent research assistant to minimize bias. A summary of the planned data + collection is shown in Figure 2 + .

+ + + +

Schedule of enrollment, intervention and data collection

+

Abbreviations: BFI, Brief Fatigue Inventory, CES-D, Centre for Epidemiologic + Studies Depression; PSQI, Pittsburgh Sleep Quality Index.

+ + + + + Basic demographic data +

Participants’ basic characteristics (sex, marital status, age) and cancer + history will be collected using a self-designed questionnaire.

+ + + Feasibility outcomes +

Feasibility will be assessed based on recruitment rate, retention rate, class + attendance, home practice adherence, the nature and extent of missing data, and + safety. Safety will be monitored and assessed based on total number of Adverse Event + and the presence of any Serious Adverse Event. + 75 +

+ + + Patient-reported outcomes and cortisol biomarker + + +

i. Patient-reported outcomes

+ + +

Participants will complete several patient-reported outcome measures to evaluate + fatigue—Brief Fatigue Inventory (BFI), + 68 + + sleep quality—Pittsburgh Sleep Quality Index (PSQI) + 76 + + and depression—Centre for Epidemiologic Studies Depression (CES-D)77,78 at Week-1, Week-6, + Week-12, and Week-16.

+ + +

a. Fatigue—The Brief Fatigue Inventory (BFI)

+ + +

The BFI was developed for the rapid assessment of fatigue severity in cancer patients + for use in both clinical screening and clinical trials. It is easy to administer, and + patients can complete them easily as it has only 9 items with simple wordings that are + easy to understand and translate. + 68 + + Items 1 to 3 rate participants’ worst, usual, and current fatigue during the + past 24 hours using a visual analog scale (VAS) ranging from 0 (no fatigue) to + 10 (very severely fatigued). A composite fatigue severity score was obtained by + averaging the 3 severity scores. The remaining 6 items rate the level at which + patients` fatigue interferes with certain functions such as daily activity, work, + walking ability, normal work, relations with others, and enjoyment in life. Each item + is rated on a scale of 0 (does not interfere) to 10 (completely interferes). A + composite fatigue interference score will be obtained by averaging the scores of the 6 + interference items. Severity scores of 1 to 3 suggest mild fatigue, 4 to 6 moderate, + and 7 to 10 represent severe fatigue. The internal consistency Cronbach’s + α at .96 supports the reliability of BFI which is correlated with measures of + performance status (patients who are more ill reported higher levels of fatigue). + 68 +

+ + +

b. Sleep—Pittsburgh Sleep Quality Index (PSQI)

+ + +

The PSQI, proposed by Buysse et al + 76 + + in 1989, is currently the most commonly used scale for assessing sleep quality. The + PSQI is a 19-item scale measuring 7 aspects of the sleep quality and disturbances, + that is, subjective sleep quality, sleep latency, duration, efficiency, disturbances, + use of sleep medication, and daytime sleep dysfunction, each weighted equally on a 0 + to 3 scale. The total score ranges between 0 and 21, with increasing scores indicating + worse sleep quality. + 76 + + It has a sensitivity of 89.6% and a specificity of 86.5% to detect insomnia cases and + is a useful first-line, easy-to-handle, and time-efficient questionnaire to evaluate + sleep quality. + 79 + + The PSQI was reported to be a stable measure of sleep quality with high test-retest + reliability and construct validity.79,80

+ + +

c. Depression—Centre for Epidemiologic Studies Depression (CES-D)

+ + +

The CES-D is a short self-reported 20-item scale + 81 + + to be administered to measure depression symptoms at baseline, mid-intervention, + post-intervention, and follow-up. The CES-D shows very high internal consistency and + adequate test-retest repeatability. + 81 + + The score is the sum of all items, and the maximum score is 60. + Scores ≥ 16 on the CES-D is considered as having + “depressed symptoms.” The cut off score of 12 has been validated with + DSM-III criteria for clinical depression.81,82

+ + +

ii. Cortisol biomarker: 24-hour urine cortisol

+ + +

Urine sample will be collected at baseline (Week-1) and post-intervention (Week- 12). + 83 + + Participants are briefed on the urine collection procedure during assessment and + advised to obtain the 2.5 L urine collection container from any nearby BP + Laboratories before baseline (Week-1) and post-intervention (Week-12). We use 24-hour + urinary cortisol as a non-invasive, integrated measure of cortisol stress hormone + activity that could be collected in participants’ home environments. + Participants are instructed to collect all urine for 24 hours from 8:00am a day + prior to baseline (Week-1) and post-intervention (Week-12) to 8:00am the next mornings + and to send the urine sample collected to the nearest BP Laboratories the next morning + itself. If the 2.5L collection container is completely full, subjects are advised to + use a clean mineral water bottle to collect any specimen in excess of the 2.5 L + collection. If subjects are unable to collect all urine for any reason, their samples + will be deemed inadequate and no urinary cortisol data will be recorded for these + subjects.

+

The 24-hour urine cortisol test provides a more accurate estimate of overall cortisol + secretion + 84 + + to assess urinary-free cortisol (UFC) over a 24-hour period and provides an index of + (unbound serum cortisol) the total amount of cortisol released by the adrenals. The + 24-hour collection time reflects the amount of cortisol that is released over a + complete circadian cycle, which is a physiologically meaningful unit of time. An + integrated mean of cortisol levels over a 24-hour period is thought to provide a + moderately stable measure of adrenocortical output. + 85 + + Urinary cortisol output will be analyzed by chemiluminescent microparticle immunoassay + (CMIA) at BP Laboratories, headquartered in Shah Alam, Selangor Darul Ehsan, Malaysia.

+ + + Qualitative interview +

Semi-structured interviews will be conducted to inform interpretation of quantitative + results and participants’ acceptance, experience, and subjective perception of + the study as well as to find out areas for further improvement + 86 + + after Week-16.

+

A prepared interview guide (Supplemental Material 4) is designed to delve into + participants’ experiences and will be used in the interview to cover 3 primary + themes: the experiences of practicing GQ, changes in the physical and emotional state, + and suitability of GQ for cancer survivors. Examples of questions to be asked are + “How do you feel about the 12 weeks of Guolin Qigong study?,” + “Have you had other benefits from this Guolin Qigong study?,” and + “Would you recommend Guolin Qigong to other cancer survivors? Why? Why + not?.”

+

Each interview will take approximately 45 minutes and will be audio-recorded + and transcribed verbatim by the Researcher.

+ + + + + Protocol Amendments +

The Researcher is responsible for submitting materials to the human ethics committee.

+ + Trial Monitoring +

The Researcher will report progress of the trial to the panel of supervisors on a + quarterly basis. Annual reports will be submitted to the human ethics committee to + monitor the trial progress and outcomes. Participants in the GQ group will be advised to + record any perceived adverse events in the practice diary and this will be recorded in + participants’ Adverse Event Form by the Researcher. The severity, expectedness + and causal relationship with GQ intervention will be assessed for every adverse event + according to guidelines for safety reporting.75,87

+

The schedule of the enrollment, intervention, and data collection is shown in Figure 2.

+ + + Sample Size +

Using a small effect size (0.2) + 65 + + rather than a medium effect size (0.5) + 64 + to + achieve a more conservative estimation, the sample size is 25 cases in each group with + 90% power and two-sided 5% significance trial design. + 88 + + Allowing for a drop-out of about 20% based on previous studies,89 +-92 a total sample of 60 + (30 in each group) would be required.

+ + + Data Collection +

De-identified information will be collected and managed by assigning an identification + code to each participant. Demographic information, medical history, any occurrence of + adverse events, practice adherence and intervention outcomes during the study will be + collected and recorded on paper or electronic file.

+

Demographic information and medical history will first be collected by the Researcher. + De-identified Practice Diary, Brief Fatigue Index, Pittsburgh Sleep Quality Index, and + Centre for Epidemiologic Studies Depression will be collected at Week-1, Week-6, + Week-12, and Week-16, while the 24-hour urine cortisol results will be collected by the + research assistant at Week-1 and Week-12. Interviews will be conducted by the Researcher + after Week-16, audio-recorded, de-identified, and transcribed verbatim.

+

During the study, all data will be recorded in participant source document files in + paper format (sociodemographic data, feasibility and clinical data), administered by + independent research assistants and will be transferred to an electronic format for + storage and analysis. The 2 independent research assistants will verify and check the + data collected by each other. After all data are confirmed and checked the research + assistants will extract the data into an Excel sheet for analysis.

+

After participants have been randomized, dropout and premature termination or + withdrawal from the 2 groups at any point will be recorded along with relevant reasons. + Participants can choose to withdraw and will not be affected at any time while declining + to participate or withdrawing from the trial. In some cases, participants will + discontinue the intervention, such as illness, progression of their disease, or + inability to engage despite adjustment of the program. Participants who withdraw from + the intervention during the trial will not be replaced.

+

Interviews will be conducted after Week-16 in person or online via Zoom by the + Researcher at an appointed time. Interview sessions will be audio recorded and + transcribed verbatim using NVivo or the recording feature available in Zoom, ensuring + accurate documentation, and stored in electronic files for analysis.

+ + + Data Management +

De-identified electronic data will be stored on a password-protected computer. Files + will be accessible for review only to the research team. Specific requests will be + needed from the supervisory panel for any access by any other person. All completed + forms and study information will be de-identified and stored in a locked filing cabinet + together with consent forms at UMMC.

+

The information collected will be securely locked and only accessible to the research + personnel. The data will be de-identified for analysis and once date is coded, all + identifiable information will be destroyed. All data collected in the study will be + destroyed 7 years after publication.

+ + + + Data Analysis + + Quantitative Data +

Data analysis will be conducted by an independent statistician. Data analysis will be + by intention to treat using last observation carried forward (LOCF). + 93 + The + normality of the study data will be checked by examining the mean, median, skewness, and + kurtosis including graphical representation of the box plot, normal Q-Q Plot or + histogram. Continuous data will be summarized using descriptive statistics including the + number of observations used in the calculation (n), mean, + standard deviation (SD), minimum, median and maximum. Categorical data will be + summarized as counts and percentages of each category. Between group comparison will be + conducted using the t test, chi-square test, or Fisher exact test, as + appropriate. We will report the results for two-sided 5% tests for the primary trial + outcome. We will use generalized linear mixed model (GLMM). The outcomes of the model + will be BFI, PSQI, CES-D scores, and 24-hour urine cortisol test results. Models will + include the treatment group as a fixed effect, with time as a random effect to account + for the repeated measurements. Analyses will be conducted to identify the baseline + characteristics of the participants who may benefit most from the intervention. Model + assumptions will be checked and appropriate adjustments to the analysis will be made + where necessary. STATA® software version 17.1 (2021; Stata Corporation, + College Station, TX, USA) will be used for all analyses. Cohen’s D will be + calculated as the absolute differences between the mean change in the variable divided + by pooled variance of the change.

+ + + Qualitative Data +

The researcher will conduct an interview consisting of 6 pre-determined open-ended + questions (Refer Supplemental Material 4) that were identified from + literature review and based on research questions outlined in the study. Probing + questions will only be asked where clarification or expansion of expressed ideas is + required. Interviews will be conducted until data saturation is reached. Interview + transcripts will be analyzed using the inductive qualitative content analysis approach + to provide a comprehensive descriptive summary of the interviewee’s experience + and perception of GQ in everyday terms. + 94 + All + audio recordings of the interview will be transcribed verbatim with NVivo or Zoom. + First, to obtain an overall impression, the transcribed materials will be read several + times thoroughly. Then, sentences or phrases will be condensed and divided into + ideas/meaning units. The ideas/meaning units are further condensed, abstracted, and + conceived into the categories. All categories will be put together and compared, based + on differences and similarities and group together to create themes. This iterative + approach to analysis will be conducted until no new ideas/codes emerge and saturation is + achieved. A second reviewer will review each phase of the process. A summary of each + theme and supporting quotes from participants will be generated and shared with the + study team to review independently. Data analysis will be repeated in this manner until + a final consensus is reached on final themes to ensure validity.95,96 The Consolidated + Criteria for Reporting Qualitative Research (COREQ) + 62 + will + be used for reporting the findings.

+ + + Trial Registration and Ethical Issues +

This study has been registered with ANZCTR (ACTRN12622000688785p), was approved by + Medical Research Ethic Committee of University Malaya Medical Centre (MREC ID NO: + 2022323-11092) and recognized by Western Sydney University Human Research Ethics + Committee (RH15124).

+ + + Dissemination +

The results of this study will be reported in a PhD thesis by the first author and + submitted for publication following the rules of CONSORT in a peer-reviewed journal or + presentation using de-identified or non-identifiable information. Sensitive information + including participants’ details will not be disclosed and will be treated + strictly under the privacy and confidentiality act of Malaysia and Australia.

+ + + + Discussion +

CRF is endemic in cancer survivors with disabling effects on quality of life, + co-morbidities, independent living, and work productivity. It includes physiological + changes associated with cancer diagnosis and treatment such as cortisol dysregulation, + sleep disorders, depression, and functional disability, which further contribute to the + burden of CRF. Despite the high incidence of CRF and its symptom clusters involving sleep + quality and depression, there is no effective pharmacological intervention to prevent or + alleviate these symptoms, + 68 + + highlighting the need to study CRF and its related symptom clusters to understand the + common biological mechanisms to improve quality of life of cancer survivors. Numerous + studies have reported certain psychological and physiological benefits of Qigong for + cancer survivors, promising potential in the realm of cancer medicine. While its + definitive impact requires further extensive research, some studies suggest benefits such + as enhanced physical functioning, stress reduction, improved mental health, immune + enhancement, and improved quality of life, and that it may complement conventional + medicine as adjunct therapy by providing a holistic approach to cancer care.29,33 +-44 As research progresses, understanding its potential + role in cancer medicine could open doors to more comprehensive and patient-centric + approaches to healthcare. In this regard, GQ emerges as a unique mind-body exercise that + combines moderate and adaptive walking exercise with a pronounced focus on a specialized + breathing technique. + 97 + While + walking has been reported to improve cancer-related symptoms,57 +-60 + the incorporation of breathing technique of GQ serves to foster oxygen-carbon dioxide + homeostasis—an essential factor in cancer control and ultimately survival.60,61 As such GQ stands as a + promising avenue for addressing the cluster of symptoms associated with CRF, encompassing + sleep disorder, depression, and alterations in cortisol. However, despite this promising + potential, the comprehensive exploration of GQ’s benefits remains a yet untapped + opportunity.

+

Therefore, our hypothesis posits that the current study of GQ is a feasible intervention + that holds potential to ameliorate CRF, enhance sleep quality, alleviate depression, and + regulate cortisol levels among breast, lung, and colon cancer survivors, while + concurrently unveiling a comprehensive spectrum of benefits and barriers related to + participation and adherence to GQ training, offering invaluable insights for optimizing + and enriching the program.

+

This is the first mixed-method study comprising a randomized-controlled trial and semi + structured interview to evaluate the feasibility and benefits of GQ on CRF symptom cluster + among cancer survivors. The quantitative data from the randomized-controlled trial + complements the qualitative insights to be obtained through interviews, allowing for a + comprehensive exploration of the subjective domains of feasibility, adherence, barriers + and participants’ perceptions, experiences of GQ to help improve healthcare and + identify factors for enhancing GQ intervention effectiveness.

+

Moreover, the composition of this multidisciplinary study team comprising experts from + Western Medicine and Chinese Medicine integrating their expertise from different + perspectives will lead to robust study design, enhanced participant care, rigorous data + analysis and comprehensive interpretation of results.

+ + + Limitations +

The nature of the intervention precludes blinding of both participants and researcher. + While the researcher remains unblinded as this trial is open-label, the instructors will + not be aware of intervention allocation to minimize bias. Although including cancer + survivors across all stages enables a diverse assessment of feasibility, it potentially + limits the generalizability of the results though sub-group analysis will be conducted. + Furthermore, the reliance on self-reported data for secondary outcomes emphasizes the + necessity for incorporating objective measures like actigraphy, polysomnography, and + established scales such as the Hamilton Depression Rating Scale to ensure a comprehensive + evaluation of GQ’s impact on CRF, sleep quality, and depression. Additionally, the + predominant participation of Asian Chinese individuals highlights the need for expanded + research to comprehend GQ’s feasibility and effects among cancer survivors from + various ethnic and racial backgrounds. These limitations underscore the challenges + inherent in the study’s design and demographics, emphasizing the importance of + integrating objective measures and broadening participant diversity for more conclusive + and inclusive findings.

+

Despite the limitations, exploring GQ as a potential intervention to address existing + gaps in effective treatment for CRF and its related symptom cluster of sleep quality and + depression in cancer survivors demonstrates a forward-thinking approach in the field of + oncology. It expands on the knowledge base and promotes innovative thinking, fostering the + development of novel interventions with potential contribution to the advancement of + oncology care.

+ + + Conclusion +

The insights gained from this study may guide future design and implementation of + evidence based mind-body interventions to improve cancer survivorship.

+ + + Supplemental Material + + + sj-docx-2-ict-10.1177_15347354241252698 – Supplemental material for + Exploring Guolin Qigong (Mind-Body Exercise) for Improving Cancer Related Fatigue in + Cancer Survivors: A Mixed Method Randomized Controlled Trial Protocol + + +

Supplemental material, sj-docx-2-ict-10.1177_15347354241252698 for Exploring Guolin + Qigong (Mind-Body Exercise) for Improving Cancer Related Fatigue in Cancer Survivors: A + Mixed Method Randomized Controlled Trial Protocol by Sara L. K. Low, Gwo Fuang Ho, + Bingkai Liu, Eng-Siew Koh, Yutong Fei, Chiah Shean Teo and Xiaoshu Zhu in Integrative + Cancer Therapies

+ + + + sj-docx-3-ict-10.1177_15347354241252698 – Supplemental material for + Exploring Guolin Qigong (Mind-Body Exercise) for Improving Cancer Related Fatigue in + Cancer Survivors: A Mixed Method Randomized Controlled Trial Protocol + + +

Supplemental material, sj-docx-3-ict-10.1177_15347354241252698 for Exploring Guolin + Qigong (Mind-Body Exercise) for Improving Cancer Related Fatigue in Cancer Survivors: A + Mixed Method Randomized Controlled Trial Protocol by Sara L. K. Low, Gwo Fuang Ho, + Bingkai Liu, Eng-Siew Koh, Yutong Fei, Chiah Shean Teo and Xiaoshu Zhu in Integrative + Cancer Therapies

+ + + + sj-docx-4-ict-10.1177_15347354241252698 – Supplemental material for + Exploring Guolin Qigong (Mind-Body Exercise) for Improving Cancer Related Fatigue in + Cancer Survivors: A Mixed Method Randomized Controlled Trial Protocol + + +

Supplemental material, sj-docx-4-ict-10.1177_15347354241252698 for Exploring Guolin + Qigong (Mind-Body Exercise) for Improving Cancer Related Fatigue in Cancer Survivors: A + Mixed Method Randomized Controlled Trial Protocol by Sara L. K. Low, Gwo Fuang Ho, + Bingkai Liu, Eng-Siew Koh, Yutong Fei, Chiah Shean Teo and Xiaoshu Zhu in Integrative + Cancer Therapies

+ + + + sj-pdf-1-ict-10.1177_15347354241252698 – Supplemental material for + Exploring Guolin Qigong (Mind-Body Exercise) for Improving Cancer Related Fatigue in + Cancer Survivors: A Mixed Method Randomized Controlled Trial Protocol + + +

Supplemental material, sj-pdf-1-ict-10.1177_15347354241252698 for Exploring Guolin + Qigong (Mind-Body Exercise) for Improving Cancer Related Fatigue in Cancer Survivors: A + Mixed Method Randomized Controlled Trial Protocol by Sara L. K. Low, Gwo Fuang Ho, + Bingkai Liu, Eng-Siew Koh, Yutong Fei, Chiah Shean Teo and Xiaoshu Zhu in Integrative + Cancer Therapies

+ + + + + +

We thank Cansurvive Centre Malaysia Berhad and Breast Cancer Women Association for their + invaluable support in promoting the study through their membership base. We also wish to + express our gratitude to the two Guolin Qigong instructors, Wong Wei Ming of Shah Alam + Guolin Qigong Paradise, Selangor and Chan Lan Fong of Lake Garden Guolin Qigong, Kuala + Lumpur for their unwavering passion and dedication in teaching participants throughout the + duration of the program. Their commitment to the Guolin Qigong classes over most weekends + exemplifies their exceptional dedication to the research study. We are also immensely + thankful to the courageous and resilient cancer survivors who generously share their + personal experiences of their journey to recovery, providing encouragement and hope to the + study participants.

+ + + +

Author Contributions: Conceptualization and design: Sara LK Low, Xiaoshu + Zhu, Gwo Fuang Ho, BingKai Liu, Eng-Siew Koh, and Yutong Fei. Recruitment: Sara LK Low, + Gwo Fuang Ho, Chiah Shean Teo. Investigating : Sara LK Low. Project Administration: Sara + LK Low. Supervision: Xiaoshu Zhu, Gwo Fuang Ho, BingKai Liu, Eng-Siew Koh, and Yutong + Fei. Writing- original draft: Sara LK Low. Writing-review and editing: Sara LK Low, Gwo + Fuang Ho, BingKai Liu, Eng-Siew Koh, Chiah Shean Teo, Yutong Fei, Xiaoshu Zhu. All + authors read and approved the final manuscript.

+ + +

Availability of Data and Materials: The datasets used and/or analyzed + during the current study are available from the corresponding author on reasonable + request.

+ + +

Consent for Publication: Consent for publication is not required as there + is no details on individuals reported within the manuscript.

+ + +

The author(s) declared no potential conflicts of interest with respect to the research, + authorship, and/or publication of this article.

+ + +

Funding: The author(s) disclosed receipt of the following financial + support for the research, authorship, and/or publication of this article: This paper is + part of a PhD study and it is supported by the School of Health Science, Western Sydney + University and Chinese Medicine Centre (an international collaboration between Western + Sydney University and Beijing University of Chinese Medicine). Professor Xiaoshu Zhu and + Professor Yutong Fei who are the supervisors of the first author of this manuscript are + employed as academic by these institutes respectively.

+ + +

Trial Status: Recruitment of participants started on October 2022. The + trial is currently underway and expected to be completed by end of 2025. The protocol is + version no.3 dated 16 May 2022.

+ + +

Ethics Approval and Consent to Participate: This study has been approved + by Medical Research Ethic Committee of University Malaya Medical Centre (MREC ID NO: + 2022323-11092) and recognized by Western Sydney University Human Research Ethics + Committee (RH15124). All methods will be conducted in accordance with the ethical + standards of the declaration of Helsinki. Informed consent will be obtained from all + subjects.

+ + +

ORCID iDs: Sara L. K. Low + + https://orcid.org/0000-0001-6296-6052

+

Chiah Shean Teo + + https://orcid.org/0000-0003-1071-443X

+

Xiaoshu Zhu + + https://orcid.org/0000-0002-2909-5926

+ + +

Supplemental Material: Supplemental material for this article is available + online.

+ + + + References + + + + + + Peters + ME + + + Goedendorp + MM + + + Verhagen + CA + + + van der Graaf + WT + + + Bleijenberg + G. + + +Severe + fatigue during the palliative treatment phase of cancer: an exploratory study + . Cancer Nurs. 2014;37:139 + -145.23624602 + + + + + + + + Walling + AM + + + Weeks + JC + + + Kahn + KL + + , et + al. Symptom prevalence in lung and colorectal cancer patients + . J Pain Symptom Manag. 2015;49: + 192-202. + + + + + + + Jones + JM + + + Olson + K + + + Catton + P + + , et + al. Cancer-related fatigue and associated disability in + post-treatment cancer survivors. J Cancer Surviv. + 2016;10:51-61.25876557 + + + + + + + + Pearce + A + + + Haas + M + + + Viney + R + + , et + al. Incidence and severity of self-reported chemotherapy side + effects in routine care: a prospective cohort study. PLoS One + . 2017;12:e0184360-e0184360.29016607 + + + + + + + + Smith + TG + + + Troeschel + AN + + + Castro + KM + + , et + al. Perceptions of patients with breast and colon cancer of the + management of cancer-related pain, fatigue, and emotional distress in community oncology + . J Clin Oncol. 2019;37:1666 + -1676.31100037 + + + + + + + + Henry + DH + + + Viswanathan + HN + + + Elkin + EP + + , et + al. Symptoms and treatment burden associated with cancer + treatment: results from a cross-sectional national survey in the U.S. Support + Care Cancer. 2008;16:791- + 801.18204940 + + + + + + + + Campbell + KL + + + Winters-Stone + KM + + + Wiskemann + J + + , et + al. Exercise guidelines for cancer survivors: consensus statement + from international multidisciplinary roundtable. Med Sci Sports + Exerc. 2019;51:2375-2390 + .31626055 + + + + + + + + Tell + D + + + Mathews + HL + + + Janusek + LW. + + +Day-to-day + dynamics of associations between sleep, napping, fatigue, and the cortisol diurnal + rhythm in women diagnosed as having breast cancer. Psychosom Med + . 2014;76:519-528.25186656 + + + + + + + + Bower + JE + + + Ganz + PA + + + Dickerson + SS + + , et + al. Diurnal cortisol rhythm and fatigue in breast cancer survivors + . Psychoneuroendocrinology. 2005;30: + 92-100.15358446 + + + + + + + + Allende + S + + + Medina + JL + + + Spiegel + D + + + Zeitzer + JM. + + +Evening + salivary cortisol as a single stress marker in women with metastatic breast cancer + . Psychoneuroendocrinology. 2020;115: + 104648.32171899 + + + + + + + + Pace + TWW + + + Badger + TA + + + Segrin + C + + + Sikorskii + A + + + Crane + TE + + . The + relationship between health-related quality of life and saliva C-reactive protein and + diurnal cortisol rhythm in Latina breast cancer survivors and their informal caregivers: + a pilot study. J Transcult Nurs. 2021; + 32:335. + + + + + + + Weinrib + AZ + + + Sephton + SE + + + Degeest + K + + , et + al. Diurnal cortisol dysregulation, functional disability, and + depression in women with ovarian cancer. Cancer. + 2010;116:4410-4419.20564155 + + + + + + + + Spiegel + D + + + Hahm + B-J. + + +Sleep, + diurnal cortisol, and survival among women with metastatic breast cancer + . Eur J Psychotraumatol. 2012;3:1 + . + + + + + + + Ho + RT + + + Fong + TC + + + Chan + CK + + + Chan + CL. + + +The + associations between diurnal cortisol patterns, self-perceived social support, and sleep + behavior in Chinese breast cancer patients. + Psychoneuroendocrinology. 2013;38:2337 + -2342.23742786 + + + + + + + + Zeitzer + JM + + + Nouriani + B + + + Rissling + MB + + , et + al. Aberrant nocturnal cortisol and disease progression in women + with breast cancer. Breast Cancer Res Treat. 2016 + ;158:43-50. + 27314577 + + + + + + + + Sephton + SE + + + Dhabhar + FS + + + Keuroghlian + AS + + , et + al. Depression, cortisol, and suppressed cell-mediated immunity in + metastatic breast cancer. Brain Behav Immun. 2009 + ;23:1148-1155. + 19643176 + + + + + + + + Tell + D + + + Mathews + HH + + + Witek Janusek + L. + + +151. + Day-to-day dynamics of associations between childhood adversity and cortisol diurnal + rhythm in women diagnosed with breast cancer. Brain Behav Immun + . 2014;40:e44-e44. + + + + + + + Armer + JS + + + Clevenger + L + + + Davis + LZ + + , et + al. Life stress as a risk factor for sustained anxiety and + cortisol dysregulation during the first year of survivorship in ovarian cancer + . Cancer. 2018;124:3401- + 3408.29905941 + + + + + + + + Sephton + SE + + + Sapolsky + RM + + + Kraemer + HC + + + Spiegel + D. + + +Diurnal + cortisol rhythm as a predictor of breast cancer survival. J Natl + Cancer Inst. 2000;92:994- + 1000.10861311 + + + + + + + + Hsiao + F-H + + + Kuo + W-H + + + Jow + G-M + + , et + al. Habitual sleep-wake behaviors and lifestyle as predictors of + diurnal cortisol patterns in young breast cancer survivors: a longitudinal study + . Psychoneuroendocrinology. 2015;53: + 60-68.25591116 + + + + + + + + Sephton + SE + + + Lush + E + + + Dedert + EA + + , et + al. Diurnal cortisol rhythm as a predictor of lung cancer survival + . Brain Behav Immun. 2013;30 Suppl + :S163-S170. + + + + + + + Lu + Y + + + Qu + HQ + + + Chen + FY + + , et + al. Effect of Baduanjin Qigong exercise on cancer-related fatigue + in patients with colorectal cancer undergoing chemotherapy: a randomized controlled + trial. Oncol Res Treat. 2019;42 + :431-439.31266043 + + + + + + + + Bower + JE. + + +Cancer-related + fatigue–mechanisms, risk factors, and treatments. Nat Rev + Clin Oncol. 2014;11:597-609 + .25113839 + + + + + + + + Ma + Y + + + He + B + + + Jiang + M + + , et + al. Prevalence and risk factors of cancer-related fatigue: a + systematic review and meta-analysis. Int J Nurs Stud. + 2020;111:103707. + + + + + + + Donovan + KA + + + Jacobsen + PB + + + Andrykowski + MA + + , et + al. Course of fatigue in women receiving chemotherapy and/or + radiotherapy for early stage breast cancer. J Pain Symptom Manag + . 2004;28:373-380. + + + + + + + Wong + WM + + + Chan + DNS + + + He + X + + + So + WKW + + . Effectiveness + of pharmacological and nonpharmacological interventions for managing the fatigue-sleep + disturbance-depression symptom cluster in breast cancer patients undergoing + chemotherapy: a systematic review. Cancer Nurs. + 2023;46:E70-E80.35025770 + + + + + + + + He + X + + + So + WKW + + + Choi + KC + + , et + al. Symptom cluster of fatigue, sleep disturbance and depression + and its impact on quality of life among Chinese breast cancer patients undergoing + adjuvant chemotherapy: a cross-sectional study. Ann Oncol + . 2019;30:v840. + + + + + + + Ho + SY + + + Rohan + KJ + + + Parent + J + + + Tager + FA + + + McKinley + PS. + + +A + longitudinal study of depression, fatigue, and sleep disturbances as a symptom cluster + in women with breast cancer. J Pain Symptom Manag. + 2015;49:707-715. + + + + + + + Sprod + LK + + + Janelsins + MC + + + Palesh + OG + + , et + al. Health-related quality of life and biomarkers in breast cancer + survivors participating in tai chi chuan. J Cancer Surviv + . 2012;6:146-154.22160628 + + + + + + + + Bower + JE + + + Ganz + PA + + + Irwin + MR + + , et + al. Inflammation and behavioral symptoms after breast cancer + treatment: do fatigue, depression, and sleep disturbance share a common underlying + mechanism? +J Clin Oncol. 2011;29 + :3517-3522.21825266 + + + + + + + + Reyes-Gibby + CC + + + Wang + J + + + Spitz + M + + , et + al. Genetic variations in interleukin-8 and interleukin-10 are + associated with pain, depressed mood, and fatigue in lung cancer patients + . J Pain Symptom Manag. 2013;46: + 161-172. + + + + + + + Steel + JL + + + Kim + KH + + + Dew + MA + + , et + al. Cancer-related symptom clusters, eosinophils, and survival in + hepatobiliary cancer: an exploratory study. J Pain Symptom Manag + . 2010;39:859-871. + + + + + + + Morgan + N + + + Irwin + MR + + + Chung + M + + + Wang + C. + + +The + effects of mind-body therapies on the immune system: meta-analysis. PLoS + One. 2014;9(7):e100903. + + + + + + + Campo + RA + + + Light + KC + + + O'Connor + K + + , et + al. Blood pressure, salivary cortisol, and inflammatory cytokine + outcomes in senior female cancer survivors enrolled in a tai chi chih randomized + controlled trial. J Cancer Surviv. 2015; + 9:115-125.25164513 + + + + + + + + Gholamalishahi + S + + + Okechukwu + C + + + La Torre + G + + + Mannocci + A. + + +Effects + of Tai chi and Qigong on fatigue and quality of life in patients with breast cancer: a + narrative review of systematic reviews and meta-analyses. Cancer + Res Stat Treat. 2022;5:685- + 691. + + + + + + + Yang + L + + + Winters-Stone + K + + + Rana + B + + , et + al. Tai chi for cancer survivors: a systematic review toward + consensus-based guidelines. Cancer Med. 2021 + ;10:7447-7456. + 34533284 + + + + + + + + Liu + L + + + Tan + H + + + Yu + S + + + Yin + H + + + Baxter + GD. + + +The + effectiveness of tai chi in breast cancer patients: A systematic review and + meta-analysis. Complement Ther Clin Pract. 2020 + ;38: 101078. + + + + + + + Zeng + Y + + + Xie + X + + + Cheng + ASK + + . Qigong + or Tai chi in cancer care: an updated systematic review and meta-analysis + . Curr Oncol Rep. 2019;21:48 + .30955106 + + + + + + + + Wayne + PM + + + Lee + MS + + + Novakowski + J + + , et + al. Tai chi and Qigong for cancer-related symptoms and quality of + life: a systematic review and meta-analysis. J Cancer Surviv + . 2018;12:256-267.29222705 + + + + + + + + Huston + P + + + McFarlane + B. + + +Health + benefits of tai chi: what is the evidence? +Can Fam Physician + . 2016;62:881-890.28661865 + + + + + + + + Ni + X + + + Chan + RJ + + + Yates + P + + , et + al. The effects of Tai chi on quality of life of cancer survivors: + a systematic review and meta-analysis. Support Care Cancer + . 2019;27:3701-3716.31236699 + + + + + + + + Cheung + DST + + + Takemura + N + + + Smith + R + + , et + al. Effect of qigong for sleep disturbance-related symptom + clusters in cancer: a systematic review and meta-analysis. Sleep + Med. 2021;85:108-122 + .34303913 + + + + + + + + Song + S + + + Yu + J + + + Ruan + Y + + , et + al. Ameliorative effects of Tai chi on cancer-related fatigue: a + meta-analysis of randomized controlled trials. Support Care + Cancer. 2018;26:2091-2102 + .29564620 + + + + + + + + Fong + SSM + + + Choi + AWM + + + Luk + WS + + , et + al. Bone mineral density, balance performance, balance + self-efficacy, and falls in breast cancer survivors with and without Qigong Training: an + observational study. Integr Cancer Ther. 2018 + ;17:124-130. + 28050925 + + + + + + + + Larkey + LK + + + Roe + DJ + + + Smith + L + + + Millstine + D. + + +Exploratory + outcome assessment of Qigong/tai chi easy on breast cancer survivors. Complement + Ther Med. 2016;29:196-203 + .27912947 + + + + + + + + Klein + P. + + +Qigong + in cancer care: theory, evidence-base, and practice. Medicines + . 2017;4:2. + 28930219 + + + + + + + + Klein + PJ + + + Schneider + R + + + Rhoads + CJ. + + +Qigong + in cancer care: a systematic review and construct analysis of effective Qigong therapy + . Support Care Cancer. 2016;24: + 3209-3222.27044279 + + + + + + + + Xing + TL + + + Zhou + J + + . An + approach to the nature of Qi in TCM–Qi and bioenergy. In: + + Kuang + H + + ed. Recent + Advances in Theories and Practice of Chinese Medicine. In Tech + ; 2012:79-108. + + + + + + + Huang + S-M + + + Tseng + L-M + + + Chien + L-Y + + , et + al. Effects of non-sporting and sporting qigong on frailty and + quality of life among breast cancer patients receiving chemotherapy. Eur + J Oncol Nurs. 2016;21:257- + 265.26614591 + + + + + + + + Chen + Z + + + Meng + Z + + + Milbury + K + + , et + al. Qigong improves quality of life in women undergoing + radiotherapy for breast cancer: results of a randomized controlled trial + . Cancer. 2013;119:1690- + 1698.23355182 + + + + + + + + Low + SLK + + + Cheema + BS + + + Tan + HY + + + Birling + Y + + + Zhu + X + + . The + feasibility and effects of qigong intervention (Mind-Body exercise) in cancer patients + with insomnia: a pilot qualitative study. Integr Cancer Ther + . 2020;19:1534735420977671. + + + + + + + Wayne + PM + + + Berkowitz + DL + + + Litrownik + DE + + + Buring + JE + + + Yeh + GY. + + +What + do we really know about the safety of Tai chi?: a systematic review of adverse event + reports in randomized trials. Arch Phys Med Rehabil. + 2014;95:2470-2483.24878398 + + + + + + + + Rodrigues + JM + + + Lopes + LT + + + Gonçalves + M + + + Machado + JP. + + +Perceived + health benefits of Taijiquan and Qigong. Altern Ther Health Med + . 2023;29: 222-231. + + + + + + + Yuan + YD. + + +癌症病友康复新路 + 【The New Recovery Path for Cancer Friends]. Nationalities Publishing + House. 1994. + + + + + + + Gheyasi + F + + + Baraz + S + + + Malehi + A + + , et + al. Effect of the walking exercise program on cancer-related + fatigue in patients with acute myeloid leukemia undergoing chemotherapy. Asian + Pac J Cancer Prev. 2019;20:1661- + 1666.31244285 + + + + + + + + Baruth + M + + + Wilcox + S + + + Der Ananian + C + + + Heiney + S. + + +Effects + of home-based walking on quality of life and fatigue outcomes in early stage breast + cancer survivors: a 12-week pilot study. J Phys Act Health + . 2015;12 Suppl 1:S110-S118. + + + + + + + Chen + HM + + + Tsai + CM + + + Wu + YC + + + Lin + KC + + + Lin + CC. + + +Randomised + controlled trial on the effectiveness of home-based walking exercise on anxiety, + depression and cancer-related symptoms in patients with lung cancer. Br + J Cancer. 2015;112:438-445 + .25490525 + + + + + + + + Chiu + H-Y + + + Huang + H-C + + + Chen + P-Y + + + Hou + WH + + + Tsai + PS. + + +Walking + improves sleep in individuals with cancer: a meta-analysis of randomized, controlled + trials. Oncol Nurs Forum. 2015;42 + :E54-E62. + + + + + + + Chen + H-M + + + Tsai + C-M + + + Wu + YC + + + Lin + KC + + + Lin + CC. + + +Effect + of walking on circadian rhythms and sleep quality of patients with lung cancer: a + randomised controlled trial. Br J Cancer. 2016 + ;115:1304-1312. + 27811855 + + + + + + + + Kessel + KA + + + Lettner + S + + + Kessel + C + + , et + al. Use of complementary and alternative medicine (CAM) as part of + the oncological treatment: survey about patients’ attitude towards CAM in a + university-based Oncology Center in Germany. PLoS One. + 2016;11:e0165801. + + + + + + + Wu + WJ + + + Wang + SH + + + Ling + W + + , et + al. Morning breathing exercises prolong lifespan by improving + hyperventilation in people living with respiratory cancer. + Medicine. 2017;96(2): e5838. + + + + + + + Tong + A + + + Sainsbury + P + + + Craig + J. + + +Consolidated + criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews + and focus groups. Int J Qual Health Care. 2007 + ;19:349-357. + 17872937 + + + + + + + + Campo + RA + + + O'Connor + K + + + Light + KC + + , et + al. Feasibility and acceptability of a Tai chi Chih randomized + controlled trial in senior female cancer survivors. Integr + Cancer Ther. 2013;12(6): 464-474. + + + + + + + Larkey + LK + + + Roe + DJ + + + Weihs + KL + + , et + al. Randomized controlled trial of Qigong/tai chi easy on + cancer-related fatigue in breast cancer survivors. Ann Behav Med + . 2015;49:165-176.25124456 + + + + + + + + Campo + RA + + + Agarwal + N + + + LaStayo + PC + + , et + al. Levels of fatigue and distress in senior prostate cancer + survivors enrolled in a 12-week randomized controlled trial of Qigong. J + Cancer Surviv. 2014;8:60-69 + .24170679 + + + + + + + + Chan + A-W + + + Tetzlaff + JM + + + Gøtzsche + PC + + , et + al. SPIRIT 2013 explanation and elaboration: guidance for + protocols of clinical trials. Br Med J. 2013 + ;346: e7586. + + + + + + + Eldridge + SM + + + Chan + CL + + + Campbell + MJ + + , et + al. CONSORT 2010 statement: extension to randomised pilot and + feasibility trials. BMJ. 2016;355 + :i5239.27777223 + + + + + + + + Mendoza + TR + + + Wang + XS + + + Cleeland + CS + + , et + al. The rapid assessment of fatigue severity in cancer patients: + use of the brief fatigue inventory. Cancer. 1999 + ;85:1186-1196. + 10091805 + + + + + + National Cancer Institute. About Cancer Survivorship Research: + Survivorship Definitions. National Cancer Institute. + Published 2022. Updated 17 November 2022. Accessed January 14, 2024 + . https://cancercontrol.cancer.gov/ocs/definitions + + + + + + + Kuznetsova + OM + + + Tymofyeyev + Y. + + +Preserving + the allocation ratio at every allocation with biased coin randomization and minimization + in studies with unequal allocation. Stat Med. + 2012;31:701-723.22161821 + + + + + + Sealed Envelope. Minisation. 2022. + Updated 31 May 2022. Accessed August 5, 2023. https://www.sealedenvelope.com/help/redpill/latest/minimisation/ + + + + + + + Taves + DR. + + +Minimization: + a new method of assigning patients to treatment and control groups. Clin + Pharmacol Ther. 1974;15:443- + 453.4597226 + + + + + + + + Yang + J-M. + + +The + Root of Chinese Chi Kung: The Secrets of Chi Kung Training. Yang’s + Martial Art Association Publication Center; 1989. + + + + + + + Cohen + KS. + + +The + Way of Qigong. Wellspring/Ballantine; + 1999. + + + + + National Health and Medical Research Council. Guidance: Safety + monitoring and reporting in clinical trials involving therapeutic goods. National + Health and Medical Research Council; 2016. + + + + + + + Buysse + DJ + + + Reynolds + CF + 3rd + + + Monk + TH + + + Berman + SR + + + Kupfer + DJ. + + +The + Pittsburgh sleep quality index: a new instrument for psychiatric practice and research + . Psychiatry Res. 1989;28:193 + -213.2748771 + + + + + + + + Turvey + CL + + + Wallace + RB + + + Herzog + R. + + +A + revised CES-D measure of depressive symptoms and a DSM-Based measure of major depressive + episodes in the elderly. Int Psychogeriatr. 1999 + ;11:139-148. + 11475428 + + + + + + + + Melchior + LA + + + Huba + GJ + + + Brown + VB + + + Reback + CJ. + + +A + short depression index for women. Educ Psychol Meas. + 1993;53:1117-1125. + + + + + + + Backhaus + J + + + Junghanns + K + + + Broocks + A + + + Riemann + D + + + Hohagen + F. + + +Test-retest + reliability and validity of the Pittsburgh sleep quality index in primary insomnia + . J Psychosom Res. 2002;53:737 + -740.12217446 + + + + + + + + Gentili + A + + + Weiner + DK + + + Kuchibhatla + M + + + Edinger + JD. + + +Test-retest + reliability of the Pittsburgh sleep quality index in nursing home residents + . J Am Geriatr Soc. 1995;43:1317 + -1318.7594173 + + + + + + + + Radloff + LS. + + +The + CES-D scale: a self-report depression scale for research in the general population + . Appl Psychol Meas. 1977;1:385 + -401. + + + + + + + Andresen + EM + + + Malmgren + JA + + + Carter + WB + + + Patrick + DL. + + +Screening + for depression in well older adults: evaluation of a short form of the CES-D + . Am J Prev Med. 1994;10:77 + -84.8037935 + + + + + + + + El-Farhan + N + + + Rees + DA + + + Evans + C. + + +Measuring + cortisol in serum, urine and saliva - are our assays good enough? +Ann + Clin Biochem. 2017;54:308- + 322.28068807 + + + + + + + + Contreras + LN + + + Hane + S + + + Tyrrell + JB. + + +Urinary + cortisol in the assessment of pituitary-adrenal function: utility of 24-Hour and spot + determinations. J Clin Endocrinol Metab. 1986 + ;62:965-969. + 3958132 + + + + + + + + Yehuda + R + + + Halligan + SL + + + Yang + RK + + , et + al. Relationship between 24-hour urinary-free cortisol excretion + and salivary cortisol levels sampled from awakening to bedtime in healthy subjects + . Life Sci. 2003;73:349- + 358.12757842 + + + + + + + + Creswell + JW + + + Creswell + JD + + + (eds.). Research Design : Qualitative, Quantitative, and Mixed Methods + Approaches, 6th ed. +Sage Publications, Inc + ; 2023. + + + + + International Conference on Harmonisation of Technical Requirements for + Pharmaceuticals for Human Use. ICH GCP E6(R2) Guideline for Good + Clinical Practice. 2016. + + + + + + + Whitehead + AL + + + Julious + SA + + + Cooper + CL + + + Campbell + MJ. + + +Estimating + the sample size for a pilot randomised trial to minimise the overall trial sample size + for the external pilot and main trial for a continuous outcome variable. Stat + Methods Med Res. 2016;25:1057- + 1073.26092476 + + + + + + + + Ying + W + + + Min + QW + + + Lei + T + + , et + al. The health effects of Baduanjin exercise (a type of qigong + exercise) in breast cancer survivors: a randomized, controlled, single-blinded trial + . Eur J Oncol Nurs. 2019;39:90 + -97.30850143 + + + + + + + + Wood + AM + + + White + IR + + + Thompson + SG. + + +Are + missing outcome data adequately handled? A review of published randomized controlled + trials in major medical journals. Clin Trials. + 2004;1:368-376.16279275 + + + + + + + + Fielding + S + + + Maclennan + G + + + Cook + JA + + + Ramsay + CR. + + +A + review of RCTs in four medical journals to assess the use of imputation to overcome + missing data in quality of life outcomes. Trials. + 2008;9:51.18694492 + + + + + + + + Cramer + H + + + Haller + H + + + Dobos + G + + + Lauche + R. + + +A + systematic review and meta-analysis estimating the expected dropout rates in randomized + controlled trials on yoga interventions. Evid Based Complement + Alternat Med. 2016;2016: 5859729. + + + + + + + Jebb + SA + + + Ahern + AL + + + Olson + AD + + , et + al. Primary care referral to a commercial provider for weight loss + treatment versus standard care: a randomised controlled trial. + Lancet. 2011;378:1485-1492 + .21906798 + + + + + + + + Sandelowski + M. + + +Whatever + happened to qualitative description? +Res Nurs Health. + 2000;23:334-340.10940958 + + + + + + + + Zheng + G + + + Xiong + Z + + + Zheng + X + + , et + al. Subjective perceived impact of tai chi training on physical + and mental health among community older adults at risk for ischemic stroke: a + qualitative study. Journal of the Australian - Traditional + Medicine Society. 2017;17:108. + + + + + + + Lee + TL + + + Sherman + KJ + + + Hawkes + RJ + + + Phelan + EA + + + Turner + JA. + + +The + benefits of T'ai chi for older adults with chronic back pain: a qualitative study + . J Altern Complement Med. 2020;26: + 456-462.32379976 + + + + + + + + Yu + DY. + + +Guolin + New Qigong Practice Manual. Canada: Guo + Lin Qigong Association of Toronto. 2021. + + + +
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