Uysal et al. (2016): Effects of foot massage applied in two different methods on symptom control in colorectal cancer patients: Randomised control trial

Reference ↗
Title	Publication: Effects of foot massage applied in two different methods on symptom control in colorectal cancer patients: Randomised control trial
Topic	Reflexology
Author	Uysal, N, Kutlutürkan, S, Uğur, I
Year	2016
Journal	International Journal of Nursing Practice
DOI	https://doi.org/10.1111/ijn.12532

Brief summary

According to the survey, the arm of patients who received reflex therapy fared better in the following areas than the arms of patients who received classic foot massage or no additional treatment: Pain, fatigue, bloating, urinary urgency and quality of life in general. Some of the patients who received the classic massage also had better scores than the patients who did not receive any additional treatment, namely for pain and bloating. However, the study has serious methodological flaws, e.g. the reflex therapy patients were better off in terms of their quality of life than the other patients right from the start. In addition, they knew that they were receiving a special treatment, so this circumstance could also explain some of the effects. Furthermore, it is not stated how large or small the effects are and whether they are significant in practice.

Der Gruppe der Patienten, die Reflextherapie bekommen hat, ging es laut Befragung in folgenden Belangen besser als den Gruppen der Patienten, die klassische Fußmassage oder keine zusätzliche Behandlung bekommen haben: Schmerzen, Fatigue, Blähungen, Harndrang und Lebensqualität allgemein. Die Patienten, die die klassische Massage bekommen haben, hatten teilweise auch bessere Werte als die Patienten, die gar nichts zusätzlich bekommen haben, nämlich bei Schmerzen und Blähungen. Die Studie hat allerdings gravierende methodische Mängel, z.B. ging es den Reflextherapie-Patienten von Anfang an in Bezug auf ihre Lebensqualität besser als den anderen Patienten. Zudem wussten sie, dass sie eine besondere Behandlung bekommen, so dass auch dieser Umstand einige Effekte erklären könnte. Des Weiteren ist nicht angegeben, wie groß oder klein die Effekte sind und ob diese in der Praxis bedeutsam sind.

Study Design

Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies	Prospective
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	Monocentric
Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties	No
Is randomized	Yes
Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control	No
Number of arms	3

Study characteristics

Inclusion criteria	Patients who were older than 18 years; were examined with second and third stage colorectal cancer; received CRT during postoperative and preoperative periods; were able to speak, read, and understand Turkish; and had agreed to participate in the study.
Exclusion criteria	People who had other types of cancer, whose cancer recurred before the treatment, who had mental and psychiatric diseases, and who had contraindications for foot massage (such as disseminated edema, a pacemaker, a history of myocardial infarction, uncontrolled hypertension, active gout, deep vein thrombosis history, gallbladder or kidney stones, acute infection, fever, or a fracture or wound on the feet)
N randomized	60
Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment.	PP Analysis
Specifications on analyses	Chi square test
Countries of data collection	Turkey
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	NI

Characteristics of participants

Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors.	Palliative
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Colorectal Cancer
Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis	Advanced Stage
Specifications on cancer stages	Second- and third‐stage colorectal cancer
Comorbidities	NI
Current cancer therapies	Chemotherapy, Radiation therapy
Specifications on cancer therapies	Receiving chemoradiationtherapy during postoperative and preoperative periods
Previous cancer therapies	Diverse
Gender	Mixed
Gender specifications	50 % female
Age groups	Adults (18+)
Age groups specification	Mean = 59 years

Arms

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Intervention
Number of participants (arm) N randomized	22
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	N=2
Drop-out reasons	N=1, severe diarrhea; N=1, radiation dermatitis
Intervention	Classical massage
Dosage and regime	10 min per foot and dorsum, 2x/week, 5 weeks in total, + chemoradiantherapy,
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	10
Side effects / Interactions	NI

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Intervention
Number of participants (arm) N randomized	21
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	N=1
Drop-out reasons	Reduced thrombocyte values
Intervention	Reflexology message
Dosage and regime	Stimulation of the reflex points 20 min. of the right foot and 10 min. of the left foot, 2x/week, 5 weeks in total), + chemoradiantherapy
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	10
Side effects / Interactions	NI

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Placebo
Number of participants (arm) N randomized	22
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	N=2
Drop-out reasons	N=1, radiation dermatitis; N=1, reduced neutrophil values
Intervention	Control arm
Dosage and regime	Chemoradiantherapy, no information about duration in days
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	-999
Side effects / Interactions	NI

Outcomes

Quality of life

Outcome type As specificed by the authors	Primary
Outcome specification	QoL with EORTC QLQ C30: Functional Scale, Symptom Scale, Global Health Scale (week 1,3,5 chemotherapy)
Type of measurement	EORTC QLQ (European Organisation for Research and Treatment of Cancer Core/ Quality of Life questionnaire)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	Functional scale: Higher (better) scores in classical relfexology arm than control arm at week 3 (mean (SD): classical massage arm: 82.66 [4.42], control arm: 80.22 [8.64]; p< 0.000) and at week 5 (reflexology arm: 81.98 [4.79]; control arm: 71.66 [9.34]; p< 0.000) Symptom scale: Higher (worse) scores in reflexology arm than in control arm at week 3 (mean (SD): reflexology arm: 21.66 [22.36]; control arm: 20.00 [16.75]; p= 0.003), but lower (better) scores in reflexology arm than control arm at week 5 (reflexology arm: 25.00 [16.75]; p= 0.000). week (reflexology arm: 25.00 [32.21], control arm: 31.66 [29.56]; p< 0.000), as well as between classical massage arm and control arm at week 5 (B: 26.66 [13.67]; control arm: 31.66 [29.56]; p< 0.000) Global health scale: Higher (better) scores in reflexology arm than in control arm or classical massage arm at week 1(mean (SD): classical massage arm: 68.33 [5.72], reflexology arm: 76.25 [9.85], control arm: 68.33 [11.34]; p= 0.012) of week 3 (classical massage arm: 61.57 [9.85]; control arm: 68.33 [11.34]; p= 0.000). week (classical massage arm: 61.57 [8.56], reflexology arm: 70.55 [8.56], control arm: 60.67 [8.76]; p<0.000) and the 5th week ( B: 57.08 [9.07], reflexology arm: 69.16 [9.40], control arm: 54.16 [9.55]; p<0.000)
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NA

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Quality of life

Outcome type As specificed by the authors	Primary
Outcome specification	QoL with EORTC QLQ CR29 (week 1,3,5 chemotherapy)
Type of measurement	EORTC QLQ (European Organisation for Research and Treatment of Cancer Core/ Quality of Life questionnaire)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	No information
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NA

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Toxicity

Outcome type As specificed by the authors	Secondary
Outcome specification	Adverse effects with CTCAE: pain, fatigue, nausea, vomiting, diarrhea, constipation, flatulence, urinary urgency and proctitis (week 1-5 of chemotherapy)
Type of measurement	CTCAE (Common Terminology Criteria of Adverse Events)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	Less grade 2+ pain in both reflexology massage arm and classical massage arm than in control arm at week 4 chemoradiationtherapy (reflexology massage arm: 19.3%, classical massage arm: 30.7%, control arm: 50%; p=0.002) and week 5 chemoradiation therapy (reflexology massage arm: 16.2%, classical massage arm: 35.4%, control arm: 43.4%; p<0.001) Less grade 2+ fatigue in reflexology massage arm than in classical massage arm or than in control arm at week 3 chemoradiation therapy (reflexology massage arm: 28%, classical massage arm: 36%, control arm:36%; p=0.03), week 4 chemoradiation therapy (reflexology massage arm: 28.6%, classical massage arm: 35.7%, control arm: 35.7%; p<0.001) and week 5 chemoradiantherapy (reflexology massage arm: 30.4%, classical massage arm: 34.8%, control arm: 34.8%; p= 0.036) Lower frequency of urinary urgency with Grade 1+ in reflexology massage arm than control arm at week 5 chemoradiationtherapy (reflexology massage arm: 25%, control arm: 37.5%; p=0.044). Less grade 1+ bloating in reflexology arm than control arm at week 4 chemoradiationtherapy (reflexology arm:15.2%, control arm: 42.4%; p<0.000) and week 5 chemoradiationtherapy (reflexology arm: 20%, control arm:56%; p<0.000). More grade 1+ bloating in classical massage arm than control arm at week 2 chemoradiationtherapy (classical massage arm: 44.1%, control arm: 20.6%; p=0.033), but less bloating in classical massage arm than control arm at week 5 chemoradiationtherapy (classical massage arm: 24%, control arm:56%; p<0.000). No sig. differences between arms in nausea, vomiting, constipation, diarrhea, proctitis
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NA

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Funding and Conflicts of Interest

Funding	NI
Conflicts of Interest	According to authors no conflict of interest

Further points for assessing the study

Sample

Power analysis performed	?
- Sample size corresponds to power analysis	?
- Reasons for insufficient sample size based on power analysis	?
If no power analysis performed: at least moderate sample size (n >= 30 per arm)	?
Ethnicity mentioned	?

Alternative Explanation

Other explanations for an effect besides the investigated intervention	?
- Possibility of attention effects	?
- Possibility of placebo effects	?
- Other reasons	?

Statistics

Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing	?
Correction for multiple testing	?
Measurement of compliance	?
Consistent reporting in numbers (figures, flowchart, abstract, results)	?
Comprehensive and coherent reporting	?
Cross-over	?
- Sufficient washout period	?
- Tested for carry-over effects	?
- Tested for sequence effects	?

Interpretation of results

Effect sizes reported (clinical vs. statistical significance)	?
Side effects systematically recorded	?
Side effects considered in result interpretation	?
Ethics votum	?

Additional Notes

• Power analysis, Bonferroni correction for multiple testing, active control
• CONTRA:

No mention of blinding, although this would have been possible with regard to classic foot massage vs. reflex therapy (note: subjective outcomes, placebo effect); Reflex therapy received 30 min intervention, classic foot massage only 20 min (performance bias); Reflex therapy was not carried out by trained therapists. The arms already differed significantly from each other in the first week (baseline) on the EORTC QLQ C30 in the Global Health Scale (mean (SD): reflexology massage arm: 76.25 [9.85], classical massagel arm: 68.33 [5.72], control arm: 68.33 [11.34]; p=0.012). In addition, there are many more patients with stage III tumors in control arm (stage II/III: reflexology massage arm 10/10, classical massage arm 5/15 and control arm 3/17); No information on the results of CR29 (reporting bias); No information on effect sizes and clinical relevance ranges