Keywords chemotherapy - side-effects - mobile apps/smartphone applications - cancer patient
Introduction
In many countries, mobile-phone based technology has become an integral part of healthcare
system to render health services to the needy in the form of mobile health (mHealth),
smartphone apps, or applications.[1 ]
[2 ] Globally, cancer is accountable for around 10 million deaths in 2020.[3 ] There are different treatment modalities for cancer, and chemotherapy is one of
the most commonly used treatment of choice for cancer.[4 ] The nature of chemotherapy is to kill the cancer cells along with healthy cells,
which results in the development of certain side effects.[5 ]
[6 ]
The most common side-effects of chemotherapy include nausea, vomiting, fatigue, diarrhea,
lack of sleep, loss of appetite, pain, and hair loss.[7 ]
[8 ] The quality of life among cancer patients is affected by these side effects and
may lead to psychological distress.[6 ]
Utilization of mobile-phone based technology has been increasing in the healthcare
sector.[9 ]
[10 ] Lack of awareness on management of these side-effects at home is one of the challenging
issues for cancer patients.[11 ] This issue can be resolved with the help of mobile-based technology as the mobile
phones/smart phones have become a vital entity in our life. The mobile-based technology,
such as smart phone apps/mHealth services, can provide information in the form of
guidelines or instructions or education to the cancer patients to manage chemotherapy-associated
side-effects.[12 ]
[13 ]
A review conducted in 2018 recommended the need to develop more comprehensive interventions
through mobile technology to meet the patients' needs in the form of guidelines and
self-monitoring of side effects associated with chemotherapy.[14 ]
Use of mobile technology for self-care monitoring and reporting of the symptoms along
with alert system that focus on severity of symptoms can enhance the living quality
of cancer patients by reducing symptom burden of the chemotherapy.[15 ]
As per the background information and our knowledge, there are no existing meta-analyses
on the intervention of utilizing mobile phone technology and its efficiency to heighten
the living quality among cancer patients.
Results of this review will give intuition and support for the development of novel
mobile-based interventions in the form of mobile apps/applications for progressing
the quality of life. This review was decided to strengthen the evidence producing
the evidence on determining the clinical outcomes of the patient's using mobile phone
technology. The objective of this review is to establish the evidence related to the
efficacy of mobile phone technology for managing side effects of chemotherapy and
improving the quality of life among cancer patients.
Methods
The authors followed Joanna Briggs Institute Manual for Evidence Synthesis (Guidance
for authors to conducting systematic reviews)[16 ] and the PRISMA guidelines for the preparation of this systematic review and meta-analysis.[17 ]
Eligibility Criteria
Inclusion criteria
a) Articles published in peer-reviewed journals.
b) Study designs: randomized control trials (RCTs) and non-randomized control trials
(non-RCTs).
c) Interventions: Studies consisting of mobile-based interventions (mobile application,
smart phone App-based interventions or guidelines to manage side-effects of chemotherapy
or mHealth services.
d) Participants: The trials that included adult cancer patients (aged 18 or above
years) who were undergoing chemotherapy, and received mobile phone-based interventions
versus control/comparator group who were getting routine or usual care, across all
types of cancers, gender, race, regions, and country.
e) Settings: Conducted in rural or urban areas or Hospitals or oncology units or clinical
settings.
f) Outcomes: Studies were included if they described either a few or all side effects
of chemotherapy such as nausea, vomiting, pain, mucositis, fatigue, sleep disturbances,
diarrhea, constipation, dyspnea, urinary problems, hand foot syndrome, hair loss,
and poor quality of life.
g) Language: Trials published in English language only.
Exclusion Criteria
a) Conference abstracts, databases containing only abstracts, books, and gray literature
were excluded.
Information Sources
The databases such as Science Direct, Scopus, Cochrane Library, PubMed, and Google
Scholar were searched for the eligible trials reported between 2007 and 2020. In addition
to this, hand search of references was performed from related trials to identify the
studies based on inclusion criteria.
Search Strategy
The search strategy was developed comprehensively using keywords in congruence with
PICO terms (population, intervention, comparator, and outcome) to identify the relevant
studies by following keywords: “Cancer patients” AND chemotherapy AND “mobile application”
OR “Mobile apps” OR mHealth AND “side effects” OR “symptom management” AND “quality
of life.”
The title and abstracts screening of the retrieved studies was done based as per the
inclusion criteria. Duplicate trials were removed by screening the title and abstracts
using Reference Manager (Zotero). The two authors (UP and SJN) independently performed
screening of the retrieved abstracts based on pre-determined inclusion criteria, followed
by screening of full-text articles.
Data Collection Process
Quantitative data of the included studies were extracted independently by two authors
based on JBI experimental studies data extraction tool.[16 ] The data extraction form consisted of details such as author, year of publication,
location, study type, sample size/group, participants type and age, intervention details
and duration, outcome measures, instruments used and study findings.
Data Items
Participants: The trials that included adult cancer patients (aged 18 or above years)
who were undergoing chemotherapy, and received mobile phone-based interventions versus
control/comparator group who are under routine or usual care.
Intervention: The experimental group cancer patients had received interventions based
on mobile technology. Trials exploring the effectiveness of mobile-based interventions
(mobile application, smart phone App-based interventions or guidelines to manage side
effects of chemotherapy or mHealth services) on cancer patients undergoing chemotherapy
were included.
Comparison: The comparator group included cancer patients undergoing chemotherapy
and who received regular or routine care.
Outcome: In this systematic review, we analyze the side-effects of chemotherapy such
as nausea, fatigue, vomiting, oral mucositis, depression, numbness, anxiety, hair
loss, diarrhea. and quality of life. Meta-analysis was done for the quality of life.
Study Risk of Bias Assessment and Effect Measures
Using the Cochrane risk of bias tool, the methodological quality of the included studies
was evaluated by two independent authors (UP and SJN). It included six domains as
mentioned in [Fig. 1 ]. We found a 100% low-risk bias regarding random sequence generation, and 75% unclear
bias was noted toward allocation concealment. The details regarding the percentages
of risk of bias across all trials are reported in [Fig. 1 ].
Fig. 1 Risk of bias chart based on review authors' judgment.
Outcome of the Search
A total of 3,647 studies were found through electronic databases. Eight duplicated
were removed using Reference Manager. After screening the title and abstracts, 3,622
studies were omitted as they did not meet the criteria of this review as per the PICO.
Full-text articles assessed for the eligibility were 17, from which 7 articles were
eliminated as they were unable to fulfil the inclusion criteria. The rational to exclude
the full-text articles along with study selection and elimination process is mentioned
in the PRSIMA flow chart ([Fig. 2 ]). Finally, 10 articles were involved for qualitative narrative synthesis, of which
4 RCTs were included for meta-analysis on the variable “quality of life.”
Fig. 2 Study selection process based on the PRISMA flow chart.
Synthesis
The outcome measures of the trials that included chemotherapy-associated side-effects
and quality of life between cancer patients who received mobile phone-based technology
as intervention and the control group who were on routine care were differentiated.
A meta-analysis on the quality of life was conducted to pool the results of RCTs using
the Rev-Man v5.4 software. The intervention's effect size for the quality of life
was estimated as a continuous outcome by pooling the standardized mean difference
applying a random-effect model with 95% confidence interval (CI). I
2 value was used to analyze the heterogeneity in the included trials. The quality evidence
and the strength of the outcome (effect sizes: 0.8 and above-large, around 0.5 medium,
around 0.2-small) were measured based on the GRADE approach guidelines.[18 ]
[19 ] The findings are reported in [Table 1 ].
Table 1
Summary of finding for efficiency of mobile phone-based technology compared to routine
care for quality of life of cancer patients
Efficiency of mobile phone-based technology compared to routine care for quality of
life of cancer patients
Patient or population: Chemotherapy cancer patient's
setting:
Intervention: Mobile phone-based technology
Comparison: Routine care
Outcomes
Anticipated absolute effects* (95% CI)
Relative effect (95% CI)
No of participants (studies)
Certainty of the evidence (GRADE)
Comments
Risk with routine care
Risk with mobile phone-based technology
Quality of life (QOL) assessed with EuroQol EQ-5D Index, EORTC QLQ-C30, World Health
Quality of Life Breast Scale
The mean quality of life ranged from −1.86 to 82.2
SMD 0.31 higher
(0.17 higher to 0.46 higher)
−
803
(4 RCTs)
⊕⊕⊕○
MODERATE a
Mobile phone-based technology likely results in an increase in the quality of life.
Moderate effect size. Statistically significant at p < 0.00001. SMD of 0.317 higher represents the improved quality of life and considerable
differences between groups.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison
group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; SMD: standardized mean difference
GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of
the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to
be close to the estimate of the effect but there is a possibility that it is substantially
different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially
different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely
to be substantially different from the estimate of effect
Explanation
a. The presence of unclear risk of bias made the authors downgrade as serious
Results
Characteristics of Patients
In this systematic review, 10 clinical trials involved 1,467 cancer patients and the
number of participants ranged from 50 to 457. The mean age of the subjects was 60
years and both males and females were included, except for four RCTs, where the participants
were only females.[20 ]
[21 ]
[22 ]
[23 ] All trials measured the side effects of chemotherapy as the main outcome and three
trials measured the quality of life as the main outcome. In all trials, the interventional
group received mobile-based technology as an intervention and the control group was
under routine/usual care. The details are mentioned in [Table 2. ]
Table 2
The summary of the data of the trials
Author, year and location
Study type
Sample size/group
Participants with type of cancer
Intervention details and duration
Outcome measures
Instruments
Study findings
Kearney et al, 2009, Scotland and England, United Kingdom
RCT (advanced symptom management system (ASyMS) vs. standard care
112, IG = 56, CG = 56
Breast cancer/lung cancer or colorectal cancer
Mobile phone-based interventions providing remote monitoring with alerts based on
severity and guidelines to manage chemotherapy related side effects (4 months)
Sore throat, diarrhea, nausea, fatigue, sore throat
CSAS
A significant higher report of symptoms were observed in control group than the interventional
group (p < 0.05).
Basch et al, 2016, New York, United States of America
RCT (symptom tracking and reporting (STAR) vs. usual care)
457, IG = 227, CG = 180
Breast, genito-urinary, gynecological or lung cancer
Web-based symptom tracking and reporting (STAR) providing interface for self-reporting
12 regular symptoms come across during chemotherapy with automated e-mail alerts (6
months)
Health Reheated Quality of life (HRQL)
Euro-QoLEQ-5D Index
Significant improvement in quality of life in interventional group. (p < 0.05)
Egbring et al, 2016, Zurich, Switzerland
Three-arm RCT (regular physician support vs. mobile App vs. mobile App and physician)
139, IG (App) = 46, IG (App& Physician) = 49
Breast cancer
Novel mobile app and web-based application was given to group-B(App) and group-C (App
and physician assistant) and group-A regular physician support (control group). The
app contains features for reporting daily functional ability and severity of symptoms
(4 months)
Daily functional activity, symptoms
ECOG & CTCAE
Group C (App and physician) shown significant improvement of daily functional ability
compared to others (p < 0.05) and group B and group C reported more distinct symptoms compared to group
A (p < 0.05)
Alboughobeish et al, 2017, Ahvaz, Iran
Non-RCT (educational content in the form of mobile software vs. routine training
50, IG = 25, CG = 25
Breast, genito-urinary, gastro-intestinal, gynecological, Hodgkin lymphoma, lung cancer,
bone cancer
Mobile software was given to interventional group which provides information regarding
chemotherapy side effects and management recondensation's for nausea and vomiting
and educational clips (1 month)
Nausea and vomiting
VAS and The Khavari Oncology Scale for Vomiting
Nausea severity was declined in interventional group (p < 0.05) but no change in control group and number of vomiting was decreased in interventional
group (p < 0.05)
Di and Li, 2018 and Henan, China
Non-RCT (medical App vs. standard care
132 IG = 65, CG = 67
Naso-pharyngeal cancer
Smart phone medical app given to the interventional group which contains features
such as modules, re-examination reminder, knowledge-based information and online expert
(6 months)
Complications (oral mucositis, hearing loss, mouth opening difficulties, nasal congestion
and quality of life
EORTC- QLQ-C30
Complication were lower among interventional than control group (p < 0.05), significant improvement in quality of life in interventional group (p < 0.05)
Kim et al, 2018 Seoul, Republic of Korea
RCT (mobile game play group vs. conventional education group)
70 IG = 36, CG = 40
Breast cancer
A mobile game ILOVEBRESAT: given to the interventional group that provides education
on preventing side and encouragement of social game playing and for control group
education through brochure. (1 month)
Quality of life, depression, anxiety and physical effects such as fatigue, nausea,
numbness and hair loss
World Health Quality of Life Breast Scale, Common Terminology Criteria for adverse
events, BDI Score, Spielberger State-Trait Anxiety Scale
Interventional group shows higher quality of life than control group (p < 0.05). Interventional group reported a smaller number of adverse effects such as
fatigue, nausea, numbness and hair loss (p < 0.05)
Greer et al, 2020 California, United States of America
RCT (mobile App vs. standard care)
181 IG = 91, CG = 90
Hematological, non-small cell lung, breast, high-grade glioma, gastro-intestinal,
genito-urinary and melanoma
A mobile app administered to the interventional group which contains features such
as symptom reporting module and patient education
Symptom burden and quality of life
MD Anderson Symptom Inventory, Functional Assessment of cancer of therapy general
Between interventional and control group no difference (p > 0.05) was observed regrading
symptom severity and quality of life
Handa et al, 2020, Tokyo, Japan
RCT (app group Vs No app group)
102 IG = 50, CG = 52
Breast cancer
Breast Cancer Patient Support System (BPSS) mobile app providing self-symptoms assessment,
recommendation to for self-management of symptoms and when to consult the physicians
(3 months)
Anxiety, depression, side effects
Anxiety and Depression scale
Significant decrease in anxiety and depression scores (p < 0.05) in interventional group compared to control group. App users reported more
symptoms (side effects) compared to non-app users.
Hou et al, 2020 Taipei, Taiwan
RCT (BCSMS mHealth App vs. usual care)
112 IG = 53, CG = 59
Breast cancer
Breast cancer self-management support mHealth App which contains self-management model
that provides education and patient centered disease management and initiates them
to participate in self-care activities (3 months)
Quality of life
EORTC- QLQ-C30 and QLQ-BR23
Significant improvement in quality of life among app users compared non app users
(p < 0.05)
Rico et al, Rio Grande Do Sul, Brazil
RCT (text messages (SMS) vs. standard care)
118 IG = 59, CG = 59
Breast, genito-urinary, gastro-intestinal, lung cancer
Interventional group receives short message service which contains management guidelines
on prevention of side-effects of chemotherapy
Nausea, vomiting, diarrhea, sore throat
EORTC-QLQ-C30
Compared to control group interventional group experienced fewer side effects (p < 0.05)
Abbreviations: CSAS, Chemotherapy Symptom Assessment Scale; ECOG, Eastern Cooperative
Oncology Group Performance Status, CTCAE, Common Terminology Criteria for Adverse
Events; VAS, visual analog scale for nausea; EORTC-QLQ-C30, European Organization
for Research and Treatment of Cancer Quality-of-Life Questionnaire Core; QLQ-BR23,
EORTC Breast Cancer-Specific QLQ.
Effects of intervention: The quality of life was analyzed as a major outcome in this
meta-analysis. The effectiveness of mobile-based technology interventions was calculated
based upon the difference between intervention group and control group post test scores.
A total of 10 trials were included for narrative synthesis that showed a significant
decrease in symptoms/side effects and improved quality of life in the interventional
group than in the comparison group.[11 ]
[13 ]
[20 ]
[21 ]
[22 ]
[23 ]
[24 ]
[25 ]
[26 ]
[27 ]
Statistical Analysis
The meta-analysis of four RCTs containing 803 cancer subjects concluded that a significant
improvement (p < 0.0001) in the quality of life.
It shows that the mobile phone-based technology interventions were effective in enhancing
the cancer patient's quality of life. A significant improvement in the quality of
life was revealed by random effects model using standardized mean difference (SMD = 0.31,
95% CI: 0.17, −0.46) and a significant difference (Z = 4.37, p < 0.001) was identified between experimental and control groups. The pooled studies
were homogenous (p = 0.46, I
2 = 0%). Because the four RCTs used different tools for measuring the quality of life,
the standardized mean difference with random effects model was used for effect measure
([Fig. 3 ]).
Fig. 3 Effectiveness of mobile phone-based technology on the quality of life.
Publication Bias
Publication bias was not evaluated as only four trials were incorporated for this
meta-analysis.
Evidence of Quality
There was a moderate quality of evidence for the assessed quality of life due to an
unclear risk of bias ([Table 1 ], [Fig. 1 ]).
Discussion
This systematic review gives evidence that mobile phone technology interventions (mobile
applications, smart phone App-based interventions, or guidelines to handle the complications
of chemotherapy or mHealth services) reduced the side effects/symptoms and improved
the chemotherapy cancer patient's quality of well-being.
Our review included 10 trials published between 2007 and 2020, identified all studies
reporting that chemotherapy-associated side-effects were reduced and enhanced the
quality of life. All the studies showed favorable outcomes.
Four trials were incorporated in this meta-analysis to evaluate the effectiveness
of mobile phone technology interventions among cancer patients regarding the changes
in the quality of life. Out of four, two trials revealed significant favorable change
in the quality of life, another two trials showed improvement in the quality of life
but results were not significant. However, the pooled result of all four trials showed
that the mobile phone technology interventions significantly improved the quality
of life.
This systematic review identified that physical effects such as nausea, vomiting,
diarrhea, sore throat (oral mucositis) fatigue, and psychological effects such as
depression and anxiety were the most common side-effects experienced by the cancer
patients under chemotherapy. These findings are congruent with those of previous studies
that highlighted the common side effects experienced by the cancer patients under
chemotherapy.[5 ]
[6 ]
The outcome of our systematic review was supported with the previous systematic reviews
that highlighted that mobile phone technology interventions had helped to minimize
chemotherapy complications and improved cancer patient's quality of life.[7 ]
[14 ]
The findings of this review will encourage healthcare professionals and organizations
to develop innovative methods using mobile phone technology that can help cancer patients
to manage the side effects associated with chemotherapy by themselves in their respective
home settings. However, mobile phone-based technology alone may not enhance the well-being
of cancer patients. The outcome of this review might disburse the opportunity for
the usage of mobile phone-based technology for rendering the healthcare services to
the cancer patients.
Limitations
Trials published in English language only were included for this systematic review,
thereby raising the chances for language bias. Publication bias was not assessed due
to restricted number of trials in the meta-analysis.
Conclusion
The evidence of this systematic review and meta-analysis supported that mobile phone-based
interventions help to improve the quality of life by minimizing the side-effects associated
with chemotherapy among cancer patients. As there is a rapid growth of using mobile
phone/smart phones by everyone, incorporating mobile phone technology in delivering
the health services is becoming very easy. However, caution needs to be taken in guiding
the users about the proper way of utilizing the technology-based services. There is
a need for further high quality of evidence through trials for effective implementation
of mobile-based technology services for cancer patients.
