Acupuncture and reexology for patients undergoing chemotherapy: an observational study

Purpose Around three quarters of individuals undergoing chemotherapy self-report multiple symptoms. There is clinical trial evidence of effectiveness for acupuncture for commonly experienced symptoms, and emerging evidence for reexology, but little is known about the effects of these therapies on multiple symptoms when implemented in a real world setting during active chemotherapy treatment. This was a single-arm observational study of participants receiving reexology and/or acupuncture while attending chemotherapy. Participants received a 20 minute reexology treatment or a 20 minute acupuncture treatment or a combination of both. Patient reported outcome measures were administered before and after the treatment using the Edmonton Symptom Assessment Scale (ESAS).


Introduction
Chemotherapy side effects impact quality of life, psychological wellbeing and may impact on capacity to tolerate a full dose of treatment. Around three quarters of individuals undergoing chemotherapy selfreport multiple symptoms the most frequent being fatigue, anxiety, nausea and bowel disturbances [13]. Complementary therapies are increasingly being incorporated into supportive cancer care to assist patients in managing these symptoms.
Acupuncture is increasingly used globally for cancer symptoms and side effects. It is offered across all National Institutes of Health cancer centres, and incorporated in ASCO endorsed guidelines [10,11].
Randomised controlled trials (RCT) have demonstrated bene t for anxiety, depression, insomnia, vasomotor symptoms and other symptoms experienced by patients undergoing chemotherapy [10].
Acupuncture has been shown to be safe, and may provide an option for patients.
Re exology is a non-invasive, localised touch therapy that is an easily administered therapeutic treatment well suited to the setting of a chemotherapy day unit. Studies have shown bene t for anxiety, sleep, pain and quality of life [15,20,21]. Together, acupuncture and re exology may also assist in managing chemotherapy induced peripheral neuropathy.
Symptoms experienced by patients undergoing chemotherapy often appear in clusters [23]. While there is evidence of the bene cial effects of acupuncture for individual symptom control in clinical trial settings, and emerging evidence for re exology, little is known about the effects of re exology and acupuncture and the treatment of multiple symptoms when implemented in a real world setting during chemotherapy treatment.
The aim of this study was to investigate if acupuncture and/or re exology improved self-reported symptoms by patients undergoing chemotherapy.

Methods
This was a single-arm observational study of participants who utilised re exology and/or acupuncture services while attending chemotherapy at the Chris O'Brien Lifehouse during the period of 2017 to 2020.
The study received ethics approval from the Sydney Local Area Health District Ethics Committee in May 2019 (HREC/18/RPAH/519.

Participants
Patients receiving chemotherapy for solid tumours in the hospital day therapy unit were offered acupuncture or re exology therapy. Participants could self-refer or be referred by healthcare professionals within the hospital. Treatments were provided free of charge to the patient, funded by a philanthropic grant to the hospital. Patients were excluded if they had profound neutropenia, thrombocytopenia (platelets < 50), selected skin conditions or risk of bruising due to their coagulation status.

Setting
The Chris O'Brien Lifehouse in Australia, operates as a non-for-pro t cancer hospital and services over 15,000 patients per year, and has a dedicated integrative oncology service [7]. The Day Therapy unit has over 45 chemotherapy chairs with 20,000 appointments annually. The acupuncture and re exology service is available twice a week, over a 90 minute period in the chemotherapy suite with an acupuncturist and a re exologist, or at times both of these. Patients were treated in either their chair while having their infusion or in a multi-chair room within the day therapy unit.

Intervention
Participants received a 20 minute re exology treatment or a 20 minute acupuncture treatment or, if requested and available, a combination of both. Where participants were undergoing an infusion through their arm that limb was typically not included in the acupuncture points selected. Acupuncture points were restricted to those that could be safely administered while the patient was seated. Therapists had a minimum of 5 years' experience working with cancer patients, and were credentialed to work within the hospital setting.
Outcome measure Patient reported outcome measures were administered before and after the treatment using the Edmonton Symptom Assessment Scale (ESAS) [1]. The ESAS R includes nine symptoms rated on a visual analogue scale (VAS) from 0 to 10. We used a modi ed ESAS-17 which includes the core items with eight additional items relevant to patients with cancer (sleep, wellbeing, spiritual pain, nancial distress, hot ashes, numbness/tingling, dry mouth and memory). Participants completed the initial ESAS prior to treatment and were asked to select a value that related to how they felt in the last 24 hours.
Immediately after treatment, they were asked to report on how they felt "right now". The ESAS has three subscales: the physical distress score (PHS), a composite of six symptoms -pain, fatigue, nausea, drowsiness, appetite and shortness of breath (0-60); the psychological stress score (PSS), a sum of depression and anxiety (0-20); and the global distress score (GDS) a sum of the PHS, PSS and well-being (0-90) [8]. The higher the score, the more distress.
The ESAS was administered by a research assistant not providing treatment to minimise administration bias. Basic demographic data, and primary cancer diagnosis were extracted from the electronic medical record.

Statistical analysis
Statistical analysis was conducted using the statistical software R version 4.0.2 [16]. Descriptive statistics were used to analyze demographic information. In order to correct for repeat treatments, generalized estimation equation methods were used to compute means, standard deviations, and tests for changes from baseline, for the ESAS symptom scores and composite scores.
A separate analysis of the mean was calculated for the different therapy groups (acupuncture, re exology, combined). Paired t-tests were used to determine the change in scores in mean and standard deviation.

Results
During the study period, 330 unique participants with a cancer diagnosis received acupuncture and/or re exology treatments while undergoing chemotherapy. Participants were mainly female (79%) with breast cancer (31%), and a median age of 56 (Table 1).

Baseline presenting symptoms
The most prevalent symptoms (ESAS≥1) of any therapy were poor sleep (85%), fatigue (85%) and decreased sense of well-being (95%) ( Table 1). Presenting symptoms were similar across acupuncture, re exology and acupuncture/re exology therapies. The symptom change for all participant encounters receiving any therapy was statistically signi cant for all symptoms. and clinically signi cant (a reduction of more than 1) for all symptoms except nancial distress, appetite and memory (Table 2).
Clinically signi cant changes were noted in overall global (GDS), physical symptom distress (PHS) and psychological stress score (PSS). For the ESAS sub-scales, there were clinically and statistically signi cant mean changes for the global distress score (-8.01), the physical (-5.15) and the emotional distress score (-2.44).
Number of symptoms: Participants had, on average, 5.3 moderate to severe (≥4/10) symptoms before treatment (Supplementary File: Table S1). Following treatment, participants reported 3.2 symptoms as moderate to severe.

Clinical response rates
Clinical response rates, de ned in the methods, were highest for fatigue (63%) and well-being (61%) ( Table 3). Pain (46%) and anxiety (43%) improvements were also experienced with a slightly higher response for pain in the re exology group (49%v44%) and anxiety in the acupuncture group (49%vs43%).

Discussion
This is one of the rst observational studies to examine the effects of acupuncture and re exology on patient reported symptom burden while undergoing chemotherapy in a routine care setting. Overall, patients receiving either or both therapies were likely to experience a clinically signi cant change in all symptoms except appetite, nancial distress and memory. Clinically signi cant reductions in global distress (a reduction of more than 3 points) was reported in 72% of all participants using any therapy, with a mean reduction of 8 on the 90-point scale. There was no statistically signi cant difference between the responses to the therapies participants were given.
The most prevalent symptoms in our study for those presenting for acupuncture were sleep disturbance, fatigue and reduced appetite, and are consistent with frequently reported symptoms in other studies of cancer patients using acupuncture in a hospital setting [6,9].
To date most studies directed at reducing the symptom burden of patients undergoing chemotherapy, have focused on self-help, nurse-led intervention, psychoeducation and cognitive behavioural therapies with mixed results [3,5,22]. Other non-pharmacological approaches speci cally for symptom clusters in patients undergoing chemotherapy have included self-acupressure, and guided imagery [2].
Our study indicates that the use of re exology for reducing the symptom burden of patients during chemotherapy may provide bene t. This is consistent with other studies, however, evidence limitations include small sample size and quasi-experimental designs [20].
Several studies have investigated acupuncture and re exology speci cally for a single symptom such as nausea and/or vomiting but few on the use of either acupuncture or re exology for the reduction of several symptoms during chemotherapy [4,12,17,19]. Re exology and acupuncture may be an option for patient to address multiple symptoms or symptom clusters with the exibility to address changes over the course of treatment [14].

Limitations
This study was undertaken at a single cancer centre and may not be generalizable to other settings. Without a control group it is di cult to predict the placebo effect or the effect of simply being in a quiet, reclining environment for 20 minutes. This study did not control patient interaction with other staff, patients or friends during intervention and more accurately re ects real world practice.
We did not control for supportive care medications and this may have impacted on self-report symptoms.
We also cannot eliminate selection bias. Participants were free to choose if they were interested in the intervention, and which intervention they preferred.
Although the service was initially offered only for 90 minutes one day a week, we expanded to two days and these days remained xed. The re exology service was available more frequently than the acupuncture.
Future research would include an active control group, factor in statistical measures for selection bias and consider confounding factors such as chemotherapy stage and medication. Research may also consider quality of life following chemotherapy, impact on dose delays, dose reductions, and reduced relative dose intensity (RDI) rates, and medication rates.

Conclusion
Acupuncture and re exology can safely be administered alongside chemotherapy in the chemotherapy chair/suite to produce a clinically signi cant reduction in patient global symptom distress, physical and psychological distress and reported symptom burden. The results of the current study support the importance of advancing the investigation of acupuncture and re exology for the management of individual symptoms and symptom clusters that occur within the context of cancer treatments.

Declarations
Funding This research was supported by a donation from the McNiven family and Mostyn family. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. contributed to the data, data collection and cleaning. GH and SG performed the analysis. All members contributed to writing the nal paper.
Ethics approval