Abstract
Objectives
To identify changes in the healthcare preferences, patient experiences, and quality of life of patients with NETs at 6-month follow-up, informing the design of supportive care services.
Methods
This study presents 6-month follow-up data of a mixed-methods multi-site study. Demographic, clinical, and patient-reported outcome questionnaire data was collected.
Results
High percentages of suboptimal experiences of care were reported. Patients reported less positive experiences with being involved in decisions about their care and treatment; their family or someone close to them having the opportunity to talk to their cancer doctor, or having their family or someone close to them receive all the information they need to help care for them at home. Patients also reported negative experiences for on the information about their cancer accessible online and the usefulness of the information they accessed. Differences between baseline and follow-up scores were mostly not significant apart from anxiety and sleep disturbance scales,
Conclusions
Patients with NETs report difficulties in accessing and understanding written information that is persistent over time.
Practice implications
Outcomes will inform the design and development of an informational resource aimed at facilitating improved understanding for patients with NETs.
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Background
Considered to be rare, neuroendocrine tumours (NETs) are a heterogeneous group of malignancies that are becoming more prevalent worldwide [1, 2]. Within the USA, population-based retrospective cohort studies have found incidence rates have increased 6.4 fold over the past five decades [3]; and similarly in Canada, incidence rates had increased from 2.48 to 5.86 per 100,000 per year [4]. Prognostic factors, such as primary site of the NET, tumour stage, and pathological grade, have been reported to predict survival outcomes for people with NETs [5, 6]. Although most commonly found in gastrointestinal and bronchopulmonary sites [1, 7, 8], NETs can originate almost anywhere in the body, and therefore survival rates can also vary [6, 9]. The severity of symptoms associated with NETs and symptom burden can also differ between patients. Depending on the secretory potential of the tumour, tumours that secrete hormones and are functional in nature can lead to clinical syndromes that produce highly distressing symptoms for patients. For others, the presentation of NETs that are non-functional can be indolent and asymptomatic in nature even with widespread disease [10, 11]. Like many other rare cancers, due to their non-specific presentation and the lack of awareness within the community and in clinical settings [12], NETs are poorly understood.
Navigating through a diagnosis of NETs presents unique challenges for both patients and clinicians. First, attaining an accurate diagnosis is often delayed due to the nature of symptoms patients present with; commonly misdiagnosed with conditions such as irritable bowel syndrome or dyspepsia [13,14,15]. Patients report difficulties in navigating through unclear treatment pathways and disease management with no disease-specific supportive care available that addresses the specific needs of the NET patient population [16]. Low levels of satisfaction with the organisation of care have also been reported and are often associated with impaired psychosocial function and increased anxiety [17].
The priority of needs reported by the NET patient population has predominantly been within psychological, physical, and daily living, and health system information domains, with information needs being most prevalent for patients diagnosed within the previous 6 months [18, 19]. However, despite the prominent need for disease-related information, it has been previously found that 69% of newly diagnosed patients reported either not receiving any written information about their cancer, or when it was received, not understanding it. Most patients access disease-related information online [20]; nevertheless, two-thirds of newly diagnosed NET patients do not find the online information resources useful [19].
Information needs are known to be greatest at diagnosis and at the start of treatment, declining over time [21]. We have previously reported that, at diagnosis, patients with both functioning and non-functioning NETs report disease-specific information to be of a high priority [19]. Specifically, most patients reported negative experiences with understanding the explanation of what was wrong with them (67%), receiving written information about their cancer (69%), their family/carer receiving all the information required to care for them (61%), and the usefulness of information about NETs online (66%). Most reported at least one moderate-to-high need for disease-specific information (63%) [19].
The aim of this study was to identify any changes in the care preferences, patient experiences, and quality of life (QoL) of patients with NETs at 6-month follow-up. We sought to understand if anxiety, depression, fatigue, pain interference, pain intensity, sleep disturbance, physical function, satisfaction with social roles and activities, supportive care needs, and experiences of the health care system, as well as general and disease-specific health-related QoL and clinical characteristics, changed over time.
Methods
Study design and setting
This study constitutes an analysis of data from phase one of a three-phase mixed methods study as outlined in the published protocol [22]. Quantitative data was collected at baseline (within 6 months from diagnosis) and then 6 months later. Ethics approval was obtained for this study from the Human Research Ethics Committee (HREC) of Peter MacCallum Cancer Centre (16/08L) and other participating sites (Royal North Shore Hospital and Northern Cancer Institute, NSW; the Lyell McEwin Hospital, SA; Royal Brisbane Hospital, QLD; and the Fiona Stanley Hospital, WA).
Eligibility and recruitment
Eligibility criteria were as follows:
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1.
A histologically confirmed diagnosis of a NET within the past 6 months
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2.
A NET classified as either functioning or non-functioning by their treating oncologist
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3.
Aged 18 years of age or older
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4.
Able to speak and read English
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5.
Well enough to participate in the study as determined by the patient’s treatment team, and no psychological or cognitive difficulties that would preclude study participation as determined by the patient’s treatment team based on a cognitive and/or psychiatric assessment or the patient’s disclosed medical history.
Patients were withdrawn if their cancer could no longer be detected or if they withdrew consent. Histological confirmation was derived from pathology reports from tumour biopsies using the World Health Organisation (WHO) classification [23]. These sites were documented. Hereditary syndromes such as multiple endocrine neoplasia (MEN 1) were not recorded.
For each site, a researcher screened and identified potentially eligible patients. Eligibility was then confirmed by the treating clinician prior to any approach, clarifying details from the medical records. Treating clinicians also classified the patient’s tumour as either functional or non-functional based on their clinical presentation with regard to hormonal hypersecretory syndrome. The study was then described to patients, and they were provided with a copy of the Participant Information and Consent Form (PICF), a baseline questionnaire and a reply-paid envelope. Patients were given an opportunity to ask questions and were informed that their involvement in the study was completely voluntary. At the time of consent, patients were asked to sign the PICF and complete the baseline questionnaire. Patients who declined to participate were asked to provide consent for the collection of basic demographic and clinical information to support an assessment of recruitment bias. Reasons for refusal were recorded. Profiles of the psychosocial, QoL, and clinical characteristics of patients with functioning, and non-functioning NETs were then developed based on patient-reported outcome data and clinical data extracted from the electronic medical record.
Measures
Demographic and clinical information was collected from participant’s medical records. Patient-reported outcomes are listed below and described in more detail in the published protocol [22].
Patient-Reported Outcomes Measurement Information System (PROMIS®) short forms consisted of emotional distress and anxiety (short form 7a), depression (short form 8b), fatigue (short form 7a), pain interference (short form 6b), pain intensity (short form 3a), sleep disturbance (short form 8b), physical function (short form 10a), and satisfaction with social roles and activities (short form 6a); the Supportive Care Needs Survey (SCNS), a 34-item questionnaire assessing needs scales across physical and daily living, psychological, sexuality, patient care and support, and health system and information; the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), a 30-item questionnaire consisting of global health status scale, five functional scales, three symptom scales and six single items assessing dyspnoea, sleep disturbance, appetite loss, constipation, diarrhoea, and financial impact [24]; the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Neuroendocrine Carcinoid Module (QLQ-GINET21), a 21-item questionnaire incorporating five scales (endocrine, G.I, treatment, social function and disease related worries scale) and 4-single items (muscle/bone pain symptom, sexual function, information/communication function and body image), and a subset of 21 items from the National Cancer Patients Experience Survey about their experiences of the health care system following their diagnosis.
Sample size
The sample size was pragmatic based on study timeframes and resources. Over 32 months, a total number of 1155 patients were screened, 975 were ineligible (n = 932 diagnosed > 6 months, n = 25 resected before baseline, n = 9 did not read/write in English, n = 9 missing). A further 22 patients were not approached due to reasons such as no follow-up appointment, clinician discretion, and patient too unwell, and 22 patients declined to participate. The remaining 138 consented to the study. At the follow-up data collection timepoint, 100 participants had completed patient reported outcome measures (PROMs) at follow-up assessment.
Statistical methods
Scoring and analysis was undertaken in SPSS Version 25 (Chicago IL, USA). Patient-reported outcome measures were scored in accordance with developer/author guidelines. Responses to SCNS-SF items were recoded to a set of discrete variables comprising two categories: no/low need and moderate/high need. Responses to CPES items were also recoded to a set of discrete variables comprising two categories: optimal (the most positive response) and sub-optimal (less positive responses) experiences of care. Responses that indicated don’t know/can’t remember or no need for information/support were excluded. CPES items with Likert-type responses were not recoded.
Descriptive statistics were used to summarize sample characteristics, and responses to patient-reported outcome measures at baseline and follow-up, including recoded responses. Paired samples t-tests were used to compare responses to PROMIS and EORTC scales/items at baseline and follow-up. Kazis effect size (ES) estimates were used to characterise the sizes of observed differences [25]. Individual change scores on PROMIS and EORTC scales/items were recoded to a set of discrete variables comprising five categories: (1) improved by 5–9, (2) improved by at least 10 points, (3) remained stable (improved or deteriorated by less than 5 points), (3) deteriorated by 5–9 or (5) deteriorated by at least 10 points, then valid percentages calculated. These scores reflect changes in patient-reported outcomes that present clinically meaningful differences [26, 27].
Results
Study profile
The flow of participants through the study is presented in Fig. 1. In total, 100 of 123 participants with baseline PROMs data completed the follow-up assessment. The sociodemographic and clinical characteristics of these participants are summarised in Table 1. As previously described Guccione et al. (2021), differences between the experiences of patients with functioning and non-functioning NETs were not statistically significant, and therefore, results have not been stratified by NET sub-group.
Patient-reported outcomes
Descriptive statistics for responses to the PROMIS and EORTC scales/items are provided in Table 2, as are the proportions of participants whose scores improved (5–9 or > 10 points), remained stable, or deteriorated (5–9 or > 10 points) between baseline and follow-up.
Apart from differences on the Anxiety and Sleep Disturbance scales, differences between baseline and follow-up PROMIS scale scores were not significant, and 95% confidence intervals included zero. Differences on the Anxiety and Sleep Disturbance scales were small-sized (ES = 0.30 and 0.20, respectively), with 36% of participants reporting an improvement in anxiety and 33% reporting a deterioration in sleep. Greater than 20% of participants reported deterioration on fatigue, and satisfaction with social roles, and activities scales (32% and 22%, respectively). Near equal percentages of patients also reported improvements (19% and 26%, respectively).
Similarly, apart from differences on the insomnia item (ES = 0.20), differences between baseline and follow-up EORTC QLQ-C30 scale/item scores were not significant, and 95% confidence intervals included zero. Approximately, one-third (34%) of participants reported worse insomnia (at least 5 points) at follow-up. For the EORTC QLQ-GINET21, a medium-sized difference was observed on the treatment-related symptoms scale (ES = 0.55, 41% of participants deteriorated). Small-sized differences were observed on the muscle/bone pain symptom item (ES = 0.20, 33% of participants deteriorated), information/communication function item (ES = 0.25, 23% of participants improved), and the social functioning scale (ES = 0.24, 48% of participants improved). Greater than 20% of participants deteriorated across several scales; however, near equal percentages also reported improvements.
The top ten most prevalent supportive care needs at baseline and follow-up (ordered by highest to lowest percentage reporting moderate/high need at baseline) are presented in Table 3. All mapped to the psychological and health system and information needs domains.
Patient-reported experiences
Descriptive statistics for CPES items at baseline and follow-up are provided in Table 4. Responses to several items at both assessments indicated high proportions of patients with sub-optimal care experiences.
At follow-up, responses to the following items indicated high percentages of suboptimal experiences of care item 9, 44% of patients indicated a less positive experience in regards to being involved as much as they wanted to be in decisions about their care and treatment; item 17, 42% reported a less positive experience about their family or someone close to them having the opportunity to talk to their cancer doctor; item 18, 59% reported less positive experiences about having their cancer doctor or nurse specialist give their family or someone close to them, all the information they need to help care for them at home; item 19, 41% indicated a less positive experience about either themselves or their family trying to access information about their cancer online; and item 20, 71% indicated a less positive experience about the usefulness of information about NETs online.
Discussion
The majority of psychosocial outcomes and care experiences of patients with NETs at 6 months follow-up were similar to those reported at baseline (within 6 months of diagnosis); score differences on most scales/items were trivial (i.e. less than small-sized). Some small sized differences were observed; on average, insomnia and sleep disturbance were worse compared to baseline, as were muscle/bone pain symptoms. Treatment-related symptoms and body image were also worse, on average compared to baseline. This is likely attributable to more patients undergoing active treatment at follow-up compared with baseline [28]. Conversely, at follow-up, approximately one-third of patients had at least a 5-point improvement in anxiety. Whilst this was a small-sized difference, scores at both time points for all PROMIS domains did not cross mild-to-moderate thresholds and were within normative standards [29], and therefore, average scores were not considered to be of clinical significance.
Identifying how the outcomes and experiences of NET patients have changed over time is informative given there is evidence to suggest that there is a relationship between QoL and clinical severity which can change over time [30, 31]. However, domains in which a stabilisation or no change is reported at 6-month follow-up are equally important. This can provide valuable insight into the persistent and unique issues patients with NETs face. As previously published in Guccione et al. (2022), compared with general population norms, patients with NETs report significant financial difficulties. Financial toxicity is well reported in the literature [19, 32, 33], and results from this study suggest these are persistent, with 84% of participants reporting ongoing or worsening financial problems compared to baseline.
While there was a small-sized improvement in information/communication function overall (QLQ-GINET21), only 23% of patients exhibited a meaningful improvement based on individual scores. High percentages of patients were still reporting either not receiving written information or for those who are receiving written information, not finding it useful (CPES), 6 months after baseline data collections. From the sample, 57% of NET patients are also still reporting at least one moderate-to-high health system information needs (SCNS-SF). The inadequacy of provision of information and the dominant theme of unmet information needs is a reoccurring one 6 months beyond initial reporting at baseline. Information needs of people with cancer are typically highest during the early stages of their diagnosis [34]. Research has found that across various cancer diagnoses, information needs will also begin to decline beyond 4 months from diagnosis [35]; however, this was observed in only 22% of this sample.
Information needs are persistently a high priority for patients with NETs, most likely due to the low provision of information. Patients with NETs continue to report difficulties in accessing and understanding written information that is persistent over time. There are many benefits of being adequately informed. Improved knowledge has been reported to provide patients with a sense of empowerment and is associated with reducing anxiety [36, 37]. Whilst information from online resources is often reported as preferred source in large proportions of people who are diagnosed with cancer [20], overwhelmingly, 71% report information available online about their cancer not to be useful.
NETs are a rare and heterogeneous cancer; therefore, given the clinical variability between patients, navigating through information resources to find information that is specific and relevant can be complex. The provision of high-quality comprehensible information is essential in providing best cancer care, and yet, results from this study suggest that access to requisite information is a persistent unmet need among people with NETs. People with cancer that are poorly informed are at greatest risk of not engaging with medical decision making, experiencing greater anxiety and are also more likely to seek alternative therapies that lack scientific support [38].
Study limitations
Eligibility criteria required participants to be able to speak and read English, and therefore, the findings from this study have not included culturally and linguistically diverse populations or those that speak a language other than English. These population in particular often report worse quality of life [39], cancer outcomes, and the greatest problems with accessing information relevant to their cancer in their preferred language [40].
Treatment regimens were not controlled for in this study. Participants were undergoing a range of treatments consisting of chemotherapy, somatostatin analogues, peptide receptor, radio nucleotide Lutate, surgery, radiotherapy, or combinations of treatments. Therefore, different treatments may have had different impacts on the experiences reported by participants.
Clinical implications
The utility of improved resources and intervention packages is clear from the findings of this study. Unmet information needs are persistent for people with NETs. The development of multimodal informational resources that address the information needs of patients with NETs is essential to improve the best care for these patients.
Conclusions
The results of this study confirm the need to improve the provision of information for people with NETs. Information relevant to diagnosis and beyond is either not available/inaccessible or does not adequately meet their needs. These findings will inform the design and development of an informational resource that will facilitate patient access and understanding of information on NETs.
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Acknowledgements
We would also like to acknowledge the support of Neuroendocrine Cancer Australia who assisted in raising awareness of the study. Finally, we thank all the patients for their time and participation in this study.
Funding
Open Access funding enabled and organized by CAUL and its Member Institutions This study was funded by the Victorian Cancer Agency—grant number ECSG14002. The funding body had no role in the design of the study; collection, analysis, and interpretation of data or in the writing of this or subsequent manuscripts.
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LG, KG, PS, and MM led the design and conceptualisation of this study. LG was PI in obtaining funding for this work with all authors named CIs. LG, TP, NP, DW, DR, and MM were responsible for data collection at each of the participating sites. Data analysis was conducted by authors KG and AD, and all data interpretation conducted by LG, KG, and PS. LG drafted the manuscript, and all authors were involved in the critical revision of the manuscript and final approval.
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Ethics approval
Ethics approval was obtained from the Human Research Ethics Committee (HREC) of Peter MacCallum Cancer Centre (project number 16/08L). The study was conducted according to the NHMRC National Statement on Ethical Conduct in Human Research (2007 and updates) and the World Medical Association Declaration of Helsinki (2013 and updates).
Consent to participate
Informed consent was obtained from all individual participants included in the study.
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The authors declare no competing interests.
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Michael Michael and Penelope Schofield contributed equally to this work.
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Guccione, L., Gough, K., Drosdowsky, A. et al. The unmet information needs, quality of life, and care experiences of patients with neuroendocrine tumours (NETs) at follow-up: 6 months from diagnosis. Support Care Cancer 31, 577 (2023). https://doi.org/10.1007/s00520-023-08034-5
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DOI: https://doi.org/10.1007/s00520-023-08034-5