Introduction

Desmoid-type fibromatosis (DF) is a rare, difficult to manage mesenchymal tumour, which accounts for 3% of soft-tissue tumours [1, 2]. The reported incidence is 2–4 individuals per million per year [3]. DF usually affects patients aged between 15 and 60 years, with a peak around 30 years [4]. Approximately 85–90% of cases are associated with mutations in the β-catenin gene (CTNNB1), leading to accumulation of β-catenin protein [5]. In a minority of cases (5–10%), DF can arise in the context of familial adenomatous polyposis (FAP) [5]. Tumours can originate in almost any area of the body, most frequently extremities, trunk, abdominal cavity, abdominal wall, head and neck [5, 6]. Although not by definition ‘malignant’, the morbidity caused by this disease and its associated treatments is far from ‘benign’ [7]. The clinical course varies; tumours may progress rapidly, remain stable for many years or undergo spontaneous regression [8, 9]. Furthermore, there is no linear relationship between symptoms and size of DF lesions.

Due to its heterogeneous behaviour, there are no established, evidence-based treatment guidelines and decisions are based on consensus recommendations [5, 6]. Treatment options include surgery, radiotherapy, chemotherapy, hormonal agents and non-steroidal anti-inflammatory drugs (NSAIDS) [5, 6]. The marginal clinical benefit of these treatments coupled with potentially serious adverse effects leads to challenging management decisions. Angiogenesis inhibitors, such as pazopanib, have shown activity in a small case-series, however, have yet to be validated in larger clinical trials [10]. More recently, the gamma-secretase inhibitor PF-03084014 has shown promising activity with clinically meaningful symptomatic benefit and durable responses in small numbers of patients [11, 12]. The optimum duration of systemic therapy remains undefined, and there are issues related to access and reimbursement of novel agents, which inevitably play an important role in the management of specific patients. Over the past decade, most specialist centres have moved away from primary surgery towards a first-line ‘watch-and-wait’ policy for asymptomatic tumours. In contrast to radical and often mutilating surgery, preservation of function and avoiding disfiguring outcomes has become a priority in the management of DF patients [5, 6].

Although desmoid tumours are incapable of metastasizing (often described as benign disease), patients sometimes undergo treatments similar to cancer patients, and experience symptoms of pain and reduced mobility and/or ability to carry out everyday activities. However, the patient’s health-related quality of life (HRQoL) has not been studied extensively. The care for DF patients may be compromised by a lack of insight into the physical, psychosocial and practical challenges they encounter. In order to optimise supportive care services, we must gain better understanding of the DF patient journey. Therefore, the aims of this study were to examine the specific challenges faced by DF patients, current care experiences and expectations of care.

Methods

Sample and procedure

Adult DF patients were recruited from the Royal Marsden Hospital sarcoma outpatient clinic. Patients were eligible if they were (1) aged ≥ 18 years; (2) diagnosed with histologically proven DF (primary or recurrent disease, any primary location, any management plan including active surveillance); and (3) could communicate in English. Patients with significant cognitive impairment or mental health problems, as determined by the referring HCP, were excluded. We employed purposive sampling to obtain a varied sample with regard to age and tumour localization.

The medical consultant, clinical nurse specialist or physiotherapist offered potential participants an information letter. With their permission, a member of the research team (OH/EY) contacted them to ask if they were willing to participate. Two focus group meetings of 120 min were scheduled at the hospital and interviews were conducted until saturation (no new topics appeared) was reached. Patients for the interviews were recruited according to an inductive design, indicating that the results of the focus groups and previous interviews shaped the recruitment for the next interviews. All participants gave written informed consent prior to the focus group or interview. Participants completed demographic, clinical and HRQoL questions before the focus group or interview. HRQoL was assessed with the EORTC QLQ-C30 [13]. This contains five functional scales (physical, role, cognitive, emotional and social functioning), a global health status/QoL scale, three symptoms scales (fatigue, nausea/vomiting, pain) and six single items assessing dyspnea, insomnia, anorexia, constipation, diarrhoea, and financial impact. Each item is scored on a 4-point Likert-scale, except general QoL, which has a seven-point Likert-scale. Scores were linear transformed to a 0–100 scale [14]. Higher score on functional scales and general QoL scale means better functioning and HRQoL, whereas a higher score on the symptom scales mean more complaints. Although developed for cancer patients, these questions can be appropriate for any respondent, e.g. ‘Do you have any trouble taking a long walk’ (physical functioning). The study was deemed exempt from full review and approval by a research ethics committee (CCR the Royal Marsden Hospital), but was approved by the service evaluation committee of the Royal Marsden Hospital (SE606).

Focus groups and interviews

Two focus groups and 13 interviews were conducted by two members of the research team (EY and OH). A semi-structured interview schedule was used (Attachment 5). Topics and questions were based on clinical experience and literature [5, 6].

Data analysis and reporting

The consolidated criteria for reporting qualitative research (COREQ) were followed to ensure accuracy of this qualitative study. The interviews were transcribed smooth verbatim using F4 software. Data analysis was conducted by two coders (OH and EY) via ATLAS.ti 8.0 using thematic analysis [15, 16]. Both coders read the transcripts several times, highlighted sections that were related to the research objectives, independently selected and coded these into key themes and subthemes. Thereafter, the coders discussed their findings, refined the key themes and subthemes, and resolved differences until consensus was reached. All quotes were anonymised.

Results

Participants

Twenty-seven patients participated (14 in focus groups and 13 interviews). Sociodemographic and clinical characteristics are presented in Table 1. DF patients scored low on all functioning scales (physical 74.4; role 55.8; social 52.8; cognitive 70.1; and emotional 56.9) and global QoL scale (56.9) of the EORTC QLQ-C30 and exceptionally high on the symptom scales pain (59.0), insomnia (56.9), fatigue (53.6) and financial difficulties (31.9).

Table 1 Sociodemographic and clinical characteristics of study participants
Full size table

DF patient journey

Analysis of the transcripts resulted in 4 main themes (diagnostic pathway; treatment pathway; living with DF; supportive care) and 12 subthemes (Fig. 1).

Fig. 1
figure 1

Schematic representation of main findings

Full size image

Diagnostic pathway (Appendix 1)

Most DF patients reported delay in diagnosis. Patients frequently did not recognise the serious nature of their own symptoms. In addition, patients experienced a long diagnostic trajectory within primary and secondary healthcare accompanied by frustration and uncertainty. Patients felt that their symptoms were not taken seriously and were transferred from ‘hospital to hospital to hospital’ to receive the correct diagnosis of DF. Several patients were initially given a diagnosis of ‘cancer’ or ‘malignant sarcoma’ and informed that the anticipated prognosis was bleak. These patients experienced shock and distress due to a cancer diagnosis and the ordeal of sharing this news with their families. Others found that receiving an incorrect diagnosis of cancer resulted in meaning-making, leading them to reassess the direction of their lives and consider positive lifestyle choices such as applying for a ‘dream job’ or instigating a ‘health kick’.

Treatment pathway (Appendix 2)

DF patients experienced uncertainty among clinicians about the optimal sequence of therapies. Patients found decisions challenging, including potentially debilitating surgery, radiotherapy or cytotoxic chemotherapy without clear evidence of treatment effectiveness. Several patients felt that there was a lack of guidance from healthcare professionals (HCP) about the most appropriate treatment and desired someone with knowledge and experience to make the best decision on their behalf. With the benefit of hindsight, some patients would have made different decisions and may have benefited from talking to others with DF. Treatment-related side effects were common and severe. Patients reported profound fatigue, loss of concentration, daily nausea, vomiting and loss of appetite, lack of libido and depression. Those who received chemotherapy suffered from ‘horrendous’ side effects including mouth ‘blisters’, ‘vomiting daily’ and ‘feeling like death’. Radiotherapy induced pulmonary fibrosis caused ‘life-changing’ breathlessness on minimal exertion.

Living with desmoid-type fibromatosis (Appendix 3)

Pain was the most debilitating symptom mentioned by all patients. Dependency on painkillers was a significant concern for several patients and others found that pain was unresponsive to analgesics. Patients reported functional limitation due to pain and restricted mobility, affecting daily activities such as bathing, dressing and carrying children. Others had to give up hobbies such as horse riding and rock-climbing. The unrelenting nature of pain and its impact on patients’ lives led to substantial psychological distress.

In addition to physical limitations, DF patients experienced difficulty accomplishing their role in society. The side effects of treatment and long-term effects of the disease caused relationship problems for several patients. Loss of libido affected sexual relationships and some reported break-down of their relationship or marriage. Patients did not want to feel as though they were a burden on their partner or family and tried to cope alone. DF patients also felt that their parental role was affected including difficulty breastfeeding, playing games with their children and depending on their partner or parent for childcare. Others felt guilty, as they did not want to burden their parents, siblings or children to the detriment of other family members. Suicidal thoughts were expressed by those who found the burden too much to bear (N = 3).

DF patients experienced changes to their employment due to their disease and found it frustrating being unable to work and wanting to feel ‘normal’. Some patients felt discriminated due to enforced sick leave, which was demoralising and led to loss of progression within their job role. In addition, financial difficulty resulting from loss of employment and hospital travel expenses was a significant concern for several patients.

Patients felt that those around them had difficulty understanding their disease, leading to frustration. At times, if not receiving active treatment, others perceived that the disease was not ‘serious’ and patients described that concern went ‘away when it’s not malignant’. Social isolation was considerable and many felt ‘alone’. Patients also felt socially behind their peers, who had greater confidence due to more experiences.

Patients described the psychological demands of living with a chronic disease that is ‘life-changing and life-long’. The uncertain behaviour of DF and fear of recurrence were mentioned by most patients. Others felt hyper-vigilant to any changes in pressure, sensation or pain, worrying that this signified deterioration in their disease. Negative body image was common, especially among women who felt ‘less feminine’ due to lumps or surgical scars. Many patients experienced depression and negative thoughts due to their disease and treatment, feeling ‘down and down and down’ and describing that they could not ‘be in that state forever’. Mood changes were common among patients.

Supportive care (Appendix 4)

All patients found it frustrating that many HCP lacked knowledge about their rare disease. Many wanted a concise information leaflet that they could present to their friends, family and others. Although treatments were similar to cancer patients, almost all patients felt that there was no specific support available for them and were turned away by cancer charities and organisations. Being treating in a cancer-specific hospital, patients felt uncomfortable, like ‘a fraud’, as if they would ‘waste time’ because others may have ‘terminal conditions’. Several patients indicated that the information provision by HCP was largely missing or could be improved. Patients were frustrated by lack of continuity and differing opinions offered by clinicians at each hospital appointment. Patients indicated that adequate psychological support was not accessible and felt it would be comforting to meet others with the same condition, whom they could contact for support and advice. They considered that face-to-face contact or online groups would be useful.

Discussion

In the present study, we found that DF patients experienced many challenges related to their diagnosis and treatment. The most commonly reported difficulties were delayed diagnosis, treatment uncertainty, treatment-related side-effects, debilitating symptoms, resulting in limitations in physical and psychosocial functioning, and financial challenges.

Most patients described a prolonged diagnostic pathway. Diagnostic delay is a common feature of rare diseases, such as DF, whereby the low prevalence leads to reduced public awareness, and lack of expertise outside specialist centres [17]. Patients’ health-seeking behaviours are complex and can be influenced by physical, social and psychological factors [18]. The clinical presentation of DF is variable. Non-specific symptoms (e.g. pain or swelling) and very low prevalence are associated with diagnostic difficulty and error in primary care [19]. Most soft tissue lumps are not ‘aggressive’ or malignant, and therefore clinical suspicion among HCP may be low [20]. It is not known whether diagnostic ‘delay’ influences overall outcomes for DF patients; however, it is undeniable that a lengthy diagnostic pathway can cause significantly psychological morbidity. Duration of diagnostic delay has been shown to be positively correlated with psychological distress among cancer patients [21]. Several DF patients received an initial diagnosis of ‘cancer’ which caused significant anxiety. Others found that confrontation with a potentially life-threatening disease provided meaning-making, prompting them to make positive changes to their lives. Regrettably, inaccurate diagnosis is not uncommon; a retrospective review of 320 specimens from DF patients found that up to one third of cases were incorrectly ascribed a diagnosis of DF [22].

Greater awareness of DF is needed among the public and HCP. The analogy of a ‘golf-ball’ has been used to increase awareness of the potentially serious nature of soft tissue lumps for soft tissue sarcomas [23]. HCP should also have easily accessible, accurate information to improve early diagnosis and provide appropriate support to patients and their families [17].

Patients reported that uncertainty among HCP about the optimal treatment strategy led to anxiety and loss of confidence in HCP. Due to the rarity of DF and lack of known meaningful endpoints, randomised phase 3 clinical trials have not been possible thus far [5]. In keeping with the standard oncological approach, most randomised phase 2 studies evaluate treatment-efficacy based on radiological endpoints and may not include other aspects which are relevant to the DF patient’s well-being [24, 25]. Consensus guidelines, based on best available evidence, aim to clarify and unify the approach to the management of DF [5]. An initial watchful waiting period is recommended followed by a multidisciplinary treatment plan for those with clearly progressive disease [5, 26]. Watchful-waiting is associated with uncertainty, fear, stress and anxiety in patients with cancer and other non-malignant conditions [27].

Patients who received an array of anti-cancer therapies reported that side-effects were underplayed by HCP. Discrepancy between patient reported outcomes and clinician-assessed toxicity has been well-described in patients treated with anti-cancer therapies [28]. Clinicians frequently underestimate the frequency and severity of side-effects which can lead to inadequate supportive care [29]. Coping with the uncertainty of treatment efficacy combined with the unpredictable natural history was extremely difficult. The treatment of rare diseases such as DF is challenging. Therapeutic options are often expensive and lack investment from pharmaceutical companies due to the small potential market. A number of drugs for DF patients, including gamma-secretase and tyrosine kinase inhibitors have shown promise in early phase clinical trials, and comparative, randomised data are needed [5]. Defining the optimal, clinically meaningful, endpoint of such studies will be challenging. Unfortunately, tyrosine kinase inhibitors that have shown benefit, are not easily accessible for DF patients as they are not licenced or reimbursed in all European countries [5]. In the absence of validated predictive factors, an individualised approach is recommended for all DF patients [26]. The risks and benefits of treatment should be carefully considered, integrating tumour location and characteristics with individual patient factors and preferences. Routinely measuring HRQoL in clinical practice and in research trials will lead to a better understanding of treatment efficacy from the patient perspective.

Due to the low prevalence and the lack of expertise DF patients are forced to become “knowledgeable” experts about their own disease. Appropriate information is largely lacking and should be developed. Careful counselling at a specialist centre, where HCP have knowledge about DF, is mandatory and should be offered to all patients affected by DF from the time of their diagnosis [5, 6]. Treatment and follow-up at a specialist centre will also improve the continuity of care.

Pain was the most debilitating symptom among DF patients. The mechanisms of pain in DF are complex and multifactorial and there is no direct correlation between pain and disease progression [5, 6]. Pain also commonly affects daily functioning in cancer survivors, especially in the first few years after treatment [30]. Numerous recommendations, which have been made to reduce pain in cancer survivors, may also be applicable to DF patients, including pain-screening and pharmacotherapy [31,30,31,34]. Due to the chronicity of DF, there is concern about the long-term adverse effects of painkillers, risks of misuse, overdose and addiction. In our study, some DF patients felt physically and psychologically dependent on painkillers. As with chronic, non-malignant pain, multimodal interventions that incorporate non-pharmacological therapies could be integrated into therapy for DF patients, aiming to restore functionality where possible.

This study showed that DF can have a considerable impact on relationships, social roles and functioning. A diagnosis of DF and/or its treatment affected finances and employment, through a reduced ability to work, need to adapt roles in the workplace and sometimes even job loss. Patients also voluntarily changed employment after self-reflection about life’s priorities. The ability to work following DF is important for maintaining self-respect, identity and living conditions [35]. Financial strain due to lost productivity and medical costs, including travelling costs to the hospital can lead to dependence on family members and have an adverse effect on patients’ social relationships.

Patients do not want to burden their partner, family or friends. DF patients sometimes feel isolated and miss out on important social activities. Most people have little familiarity with the physical and psychosocial impact of DF and may not know how to support a patient. Taking into account the relatively young patient population, patients should be supported to maintain a ‘normal’ life [5, 6].

In addition to “curing” the disease, the imperative long-term goal of any treatment strategy for DF should include maintenance or reintegration of a patient to social and work roles as far as possible. Interventions that promote social integration for DF patients (e.g. psychological and social support) and vocational counselling seem indicated.

Improved peer support may have helped DF patients to relate their experience to that of others with the same disease. For example, (online) peer-support groups and disease-specific information portals for patients with other rare disease have been shown to significantly reduce feelings of social isolation, improve knowledge, self-efficacy, problem-solving skills and effective interpersonal interactions [36,35,38]. The Royal Marsden Hospital is developing a regular clinic specifically for DF patients, which will also enable patients to meet each other at the hospital. In addition, multi-disciplinary support, involving pain specialists, physiotherapists, social workers and psychologists, should be offered to DF patients when indicated. Many patients in our study felt uncomfortable that they had to attend a clinic for patients with cancer and therefore a dedicated monthly multidisciplinary clinic (depending on the local resources) may provide a more suitable environment for their outpatient appointments.

Several limitations of this study should be taken into account. Firstly, most participants received some form of treatment and therefore may not adequately reflect the full range of DF patients. Patients on a watch and wait policy may have less problems and no treatment-related side effects. In addition, data on ethnic background were lacking, there were no Afro-Caribbean and Asian participants. Due to the limited number of patients, we could not examine gender differences with statistical probability; however, generally female patients had more problems with body image and talked more about what other people thought about their disease, while males reported uncertainty about disease growth or recurrence more often. In addition, our study sample may reflect patients who feel comfortable talking about their patient journey. We relied on patient self-report for the clinical characteristics of their disease. Our results should also be interpreted in the context of financial constraints of the UK National Health Service (NHS): leading to reduced access to certain drugs (e.g. pazopanib).

Further research is needed, preferably an international, population-based study which will integrate patient-reported outcome data with objective clinical examination, radiological findings and potentially molecular characteristics. This will allow greater insight into potential prognostic factors, treatment efficacy from the patients’ perspective and enable provision of a more holistic approach to care. Overall, DF patients face complex physical, psychological and practical challenges. Comprehensive services including improving peer-support networks are needed. Increasing awareness of this debilitating disease may also help to improve diagnostic pathways and overall patient experience.