Abstract
Background:Breast cancer-related upper limb lymphoedema (ULL) is a common sequelae of breast cancer treatment and early treatment is recommended (McLaughlin et al., 2017). Expert guidance recommends offering 2-phase decongestive lymphoedema treatment (DLT), although evidence is lacking for current treatment protocols (International Society of Lymphology, 2020; National Institute for Health and Care Excellence, 2009). However, women in the UK are routinely offered self-treatment with hosiery (Lymphoedema Framework, 2006).
Aim:
To determine the feasibility and acceptability of a trial to compare initial intensive-DLT with usual UK lymphoedema care for women newly presenting with ULL within 12 months of symptom onset (early-ULL).
Methods:
A systematic review of the evidence for clinical effectiveness of DLT for women with less than 12 months ULL duration (early-ULL) was undertaken using the Joanna Briggs Institute (JBI) method. The PICO framework was used to develop eligibility criteria and keywords for the search which was conducted in 2016, with updated searches in 2018 and 2022. The methodological quality of identified studies was assessed using the JBI critical appraisal instruments. Outcomes of interest were extracted using a form adapted from the JBI data extraction tool and results displayed in narrative and tabular format. The strength of evidence was rated using the GRADE system.
Three studies were conducted between 2015-2017 using mixed methods and pragmatic study design. Study 1 used five focus group discussions in 2015 with 13 women and 13 lymphoedema practitioners to separately explore their experiences and opinions regarding lymphoedema treatment, assessment methods, use of intensive-DLT, and acceptability of the proposed feasibility study.
Study 2 was a modified Delphi-method survey conducted as a one-day consensus event in 2015 with a panel of 13 UK expert clinicians and five service users using electronic voting technology to maintain anonymity. The survey considered five key areas of uncertainty relating to the proposed feasibility study and design of a future definitive trial, including components of the study population and proposed study interventions, treatment outcomes and defining criteria for successful and meaningful outcomes.
Study 3 addressed the feasibility of conducting a future trial of treatment effectiveness for women with early-ULL. The original protocol for a feasibility randomised controlled trial (RCT) could not be conducted because lymphoedema services lacked capacity to provide the study intervention, so was redesigned as an observational mixed methods study to address most of the original study objectives. Forty-five women-participants and 11 lymphoedema practitioners were recruited from two study sites. Women completed three study visits over a three-month period with collected data including clinical measurements of arm size and symptom severity and self-report questionnaires which explored the impact of ULL and feasibility of the proposed trial. Subsequently, a subgroup of six women and six practitioners were interviewed to explore their study experiences and the acceptability and value of lymphoedema treatment and outcome measures.
Results:
The systematic review identified eight RCT and three descriptive studies providing weak evidence (grade B) for the effectiveness of decongestive treatments for early-ULL. No study recruited only women with less than 12-months duration, so studies were included when the mean ULL duration was <9 months or findings were reported for one eligible group and the ineligible group excluded from the review. Heterogeneous data prevented comparison of findings for different treatment combinations. There is no evidence to justify change in current UK lymphoedema treatment.
Study 1 found that women typically received self-treatment with hosiery, with women and practitioners having mixed views on whether this was optimal treatment. They highlighted the lack of service capacity to provide intensive-DLT to their patients and supported the notion of early intervention but differed in views on the role of intensive-DLT. Participants supported the need for a trial to identify effective treatment for women with previously untreated ULL. No group clearly articulated criteria for a good clinical outcome and all were unsure of what were reasonable expectations of treatment and appropriate treatment goals, but they all considered arm volume an important outcome.
Study 2 found that experts agreed regarding key eligibility criteria for the future study, data collection necessary to describe ‘usual’ care, priority study outcomes and components of the comparator and one of the proposed interventions (classic intensive-DLT). They lacked sufficient expertise to agree the role of intermittent pneumatic compression within the proposed second study intervention (modified intensive-DLT) and were unable to define the criteria for treatment success or agreement on a clinically meaningful reduction in excess arm volume (EAV).
Study 3 found that most feasibility criteria were achieved, including retention to the study with 80% completing all three study visits and 99% of possible data collected. Women reported the proposed study measurements and self-report questionnaires were acceptable. ‘Usual’ care, the future comparator, was confirmed to be self-treatment with hosiery, exercise, and skin care, with simple lymphatic drainage not routinely prescribed. Recruitment was below target, due to fewer than expected eligible women, and only five had untreated early-ULL. Their presenting excess arm volume was a median 6% (minimal swelling) which is below the typical 10% threshold for ULL research. Therefore, recruitment to a future trial could be challenging and would require multiple sites. Practitioners expected capacity to screen women for a future trial but that there would be lack of capacity to deliver the study intervention. An unexpected finding was that some practitioners thought many lymphoedema clinics would be unwilling or unable to implement trial findings which favoured intensive-DLT even if this was demonstrated to be more cost-effective than usual care alone. Other original feasibility criteria that could not be tested with an observational study included the intervention processes and their acceptability and testing the effect size for calculating the sample size for the future trial.
Conclusion:
There is a lack of evidence for the most effective treatment or combination of treatments for women presenting with early-ULL, and the optimal duration and frequency of treatment is unknown. The study findings demonstrate the need and desire of women and practitioners for robust research to determine the most effective and cost-effective treatment for women with early-ULL. The findings suggest it would be possible, with sufficient time and funding, to recruit an adequate sample and conduct a definitive trial. Further work is required to address those feasibility criteria which could not be tested in this observational study and to explore factors which would affect implementation of future findings which favour intensive-DLT.
The findings suggest it is not prudent to continue with the proposed definitive trial as, due to current challenges for lymphoedema services which lack capacity to provide initial intensive-DLT, it is likely that future findings which favour intensive-DLT for women with early-ULL will not be implemented. Instead, researchers and clinicians should develop tools and strategies to equip women with knowledge and skills to improve treatment adherence and self-monitor their progress toward clearly defined and realistic goals; this should maximise treatment benefit and minimise treatment burden.
Finally, this thesis has highlighted the need for UK practitioners and women to discover what can be achieved with the best available treatment, which is likely to be a form of self-treatment, particularly for women with early-ULL. Further work is required to identify facilitators, motivators, and barriers to implementing two-phase DLT as usual care for UK lymphoedema services. The study findings also demonstrate an urgent need for a national strategy to build lymphoedema research capacity in the UK and improve lymphoedema service provision. The findings of this feasibility study will be useful to researchers intending to study treatment effectiveness for women with ULL.
| Date of Award | 1 Jul 2023 |
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| Original language | English |
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| Supervisor | Elsa Montgomery (Supervisor), Debra Bick (Supervisor), Emma Ream (Supervisor) & Cath Taylor (Supervisor) |