Living with or beyond lymphoma: A rapid review of the unmet needs of lymphoma survivors

Abstract Objective To establish an understanding of the unmet needs of people living with or beyond a lymphoma diagnosis. Survivors of lymphoma are at increased risk of unmet needs due to cancer, treatment‐related toxicities and extended survivorship. Despite the rapidly growing numbers of lymphoma survivors, their needs and research priorities are underserved and undervalued, therefore left largely unaddressed. Methods A rapid review method and reflexive thematic analysis approach assimilated current knowledge. Eligibility criteria included quantitative, qualitative, or mixed approaches employing cross‐sectional, longitudinal, cohort or review designs focused on the needs of adult lymphoma survivors (any subtype or stage of disease). Five databases: CINAHL, EMBASE, Medline, PsycInfo and Scopus, were systematically searched. Results Forty‐seven studies met the inclusion criteria via a stringent screening process facilitated by NVivo. Almost 60 per cent of articles were published within the last five years and investigated a homogenous lymphoma sample. Most studies employed quantitative approaches (77%) and cross‐sectional designs (67%). Studies were of high methodological quality. Five major themes were identified: disparity in health service delivery, the psychological impact of cancer, impactful and debilitating concerns, the monetary cost of survival and insufficient provision of survivorship information. A meta‐analytical approach was not feasible due to the breadth of methodologies of included studies. Conclusions This review shows that lymphoma survivors experience a myriad of unmet needs across multiple domains, reinforcing the need for lymphoma‐specific research. However, more research is needed to advance and achieve informed decision‐making relating to survivorship care, placing due attention to the needs and research priorities of lymphoma survivors.


| Background
Haematological malignancies are a diverse group of cancers which develop in the blood-forming tissue, including three broad categories: leukaemia, lymphoma, and myeloma. 1 Haematological malignancies are distinct from solid tumours not only regarding their pathology but also in their potential presentation, treatment, progression and outcome. 1,2 These distinguishing factors contribute to an individualised experience from diagnosis to chronic effects, with the potential for varied needs to arise from these phases. Given the diversity amongst haematological malignancies, studies of heterogeneous samples of people living with and after haematological malignancies may be inappropriate. Subtype-specific research is needed to ensure future care is responsive to survivors' needs. [3][4][5] Therefore, this review is focused on lymphoma, the largest cohort of haematological malignancies originating in the lymphatic system and encompassing a variety of distinct disease entities. 2 Given the widespread nature of the lymphatic system, lymphoma can affect any organ in the body with varying symptoms depending on where the cancer is. 6 Lymphomas are categorised into two types -Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Within the two subtypes, many variations exist. Compared with HL, NHL is more heterogenous with more than 60 subtypes and division into indolent or aggressive forms. 2,7 The varied clinical features and histological appearances of lymphoma present specific challenges such as difficult diagnosis, various management strategies and assorted prognoses. 7,8 The population of lymphoma survivors is substantially increasing thanks to the success of multimodal treatments. 9 In 2020, there were an estimated 628,000 new lymphoma cases, with 283,000 new deaths worldwide for all age groups. 10 Furthermore, the late effects of lymphoma and its treatments are critical determinants of longterm morbidity, mortality and quality of life and can pose challenges to survivorship. 7 Many lymphoma survivors will have extended life expectancies. Still, they may live with an increased risk for unmet needs resulting from late effects such as secondary malignancies, cardiac toxicity, pulmonary toxicity, and endocrine and gonadal dysfunction, which raise concerns about fertility. 2,7,11 The concept of cancer survivorship is widely interpreted. [12][13][14] However, it is broadly accepted that cancer survivorship begins at the time of diagnosis and continues until the end of life and can be referred to as 'living with and beyond cancer'. 15 Similarly, some debate and conceptual uncertainties exist on what constitutes a 'need' in healthcare. 16,17 The term 'unmet needs' distinguishes between concerns that survivors experience and wish for help in managing. 14,17,18 Efforts to improve the availability of care and resources for cancer survivors have been advanced by assessing survivors' needs. 19 The assessment of unmet needs enables the direct examination of an individual's perceived need for help. This allows for a more direct indication of required resources and the magnitude of the need for help, therefore facilitating the prioritisation of health services. 20 At the same time, identifying higher-level needs can quickly assist health care providers in recognising those most at risk and vulnerable. 21 Quantifying the prevalence of survivors experiencing difficulties, including their unmet needs, is needed to promote recovery and supportive self-management. 18,22,23 Understanding the unmet needs of lymphoma survivors can enable informed decision-making relating to survivorship care. 17,22,24 Survivorship issues are of particular importance to this population with high survival rates. 6 Yet, despite the rapidly increasing number of lymphoma survivors, their needs and research priorities rarely receive attention or are addressed. 25,26 Therefore, a rapid review has been undertaken to assess and assimilate current knowledge. 27

| Aims
This review aims to establish an understanding of the unmet needs of adults living with or beyond a lymphoma diagnosis using a rapid review method and reflexive thematic analysis approach. The research question asks, 'what are the unmet needs of people living with a diagnosis of lymphoma cancer?'.

| Eligibility criteria
To be eligible for review, publications must refer to individuals with a lymphoma cancer diagnosis at any point of survival (from diagnosis onwards), any subtype or subgroup. Outcomes must refer to the needs of these individuals. Age criteria (more than half of the sample aged 18 years or older at the time of data collection, i.e., survey) applied focus to the needs of adult survivors as opposed to childhood or adolescence. Detailed inclusion and exclusion criteria are provided in Table 1.

| Rapid review of the evidence
A rapid review method is a variation of a systematic review; this method was selected as it balances time constraints and available resources with considerations of bias. 27 The literature on the needs of lymphoma survivors includes a broad range of evidence. Therefore, this review uses a streamlined approach to synthesise the available evidence. 27 29 ; this report has broadened the BOLAND ET AL.
-1077 recognition of cancer survivorship in the cancer continuum resulting in progressive attention being placed on the unique challenges and needs of cancer and its subtypes. 30 The search was filtered to the English language only. Authors were contacted to source full text when required. Reference lists and grey literature (i.e., conference abstracts) were examined for relevance to the eligibility criteria.
However, abstracts lacked sufficient detail on population, outcomes, or results and were omitted. The search strategy and database searches were conducted by a researcher (Vanessa Boland) and an information specialist (Greg Sheaf). Key search terms related to 'lymphoma', 'cancer survivors', and 'needs' were searched; the resulting search string is outlined in Table A1.

| Study selection
First, duplicate references were removed from the review library.
Second, the title and abstract of each study were assessed for their relevance to the PEOS eligibility criteria. Two independent reviewers (Vanessa Boland and Amanda Drury) performed screening, supported by COVIDENCE software. To minimise any selection bias, discrepancies were resolved through discussion and required consensus from both reviewers. Finally, the full text of studies meeting the PEOS criteria was obtained for final screening by a single reviewer (Vanessa Boland). Secondary sources, anecdotal, opinion, editorials, minimise bias. As the goal of this review was to understand the experience of unmet needs for lymphoma survivors, rather than the effect of experimental interventions to improve outcomes, randomised controlled trials and intervention studies were also excluded.

| Quality assessment
Methodological quality was assessed for all included studies using an appraisal tool developed by the Evidence for Policy and Practice Information and Coordinating (EPPI) Centre. Studies were evaluated according to the tool's twelve quality appraisal criteria (Table A2).
One reviewer (Vanessa Boland) independently assessed each included study to establish to what extent each criterion was met, with independent verification of all judgements by a second reviewer (Amanda Drury & Anne-Marie Brady) as guided by Cochrane's interim rapid review guidance. 28 The twelve criteria measured the extent to which a study's findings provide a valuable contribution to the review. 31

| Data analysis
Reflexive Thematic Analysis (TA) formed the basis for this review's analysis due to its aptitude to amass and analyse the heterogeneous body of included literature by identifying patterns across the dataset. 32 The first step of familiarisation involves a deep immersion and analytical engagement with the data. The literature is seen as data rather than as information. Next, a code labels something of interest within the data using analysis software (NVivo version 12.0). The dataset was assessed twice to provide robust and coherent coding. Steps three to five involved organising coded data into themes and developing rich data analysis, represented by themes. 32 F I G U R E 1 Preferred reporting items for systematic reviews and meta-analyses (PRISMA) BOLAND ET AL.
-1079 3 | RESULTS Two thousand six hundred 77 studies were screened, with 391 requiring full-text eligibility review ( Figure 1). Forty-seven studies met the inclusion criteria, of which 57% were published in the last five years. Most studies employed quantitative approaches (n = 36) and were more often cross-sectional (n = 24). Studies originated from the United States (n = 15), Australia (n = 11), United Kingdom (n = 4), South Korea (n = 3) and multiple other countries located in Asia, Europe, and Oceania (Table 2). This reflects the current incidence rates of NHL, which are highest in Australia, New Zealand, Northern America and Europe. 10 Over 30 per cent of included articles explicitly investigated unmet needs as the main outcome, while others explored closely related outcomes, such as quality of life (Table 2).

| Summary of studies
Recruitment was mainly conducted via one or more cancer registries (n = 18) at hospitals, including single sites (n = 11), two sites (n = 4), three sites (n = 2) and only two studies employing online recruitment strategies (Table 2). For quantitative surveys, the most used instruments for assessing the needs (or associated outcomes, Quantitative sample sizes ranged from small to exceptionally large. The smallest sample (n = 50) was specified for a young age group, 33 and the largest sample (n = 4215) was a longitudinal study pooling data collected within clinical trials. 34 The sample sizes of qualitative studies ranged from 6 to 51 (median = 17). A homogenous lymphoma-specific population was investigated by most included studies (60%) ( Table 2). Heterogenous samples mainly included other haematological malignancies, such as leukaemia and multiple myeloma. 3,4,21,33,[35][36][37][38][39][40][41][42][43][44][45][46][47][48] Male participants were slightly more common. Most samples included participants of varying ages across adulthood (18-92 years), with four studies including participants aged 15 years or more. 21,39,49,50 Younger lymphoma survivors (<45 years) were explored by four others. 33,[51][52][53] Older adults (65-85+ years) were only examined by one study. 35 Chemotherapy was the most common treatment received by participants, with two studies focusing on outcomes relating to stem cell transplantation only. 36,54 Fourteen studies discussed the ethnicity or race of participants of these mainly White backgrounds were reported. Of the studies reporting participants' employment status, a sizeable percentage (40% -85%) were employed. A medium level of education (secondary school or equivalent) of participants in over half of the studies reporting this sociodemographic factor (n = 24) was found, while participants mainly were partnered (range 59%-98%). However, the

| Quality assessment
None of the included studies met all twelve quality criteria as this body of literature has not yet seen active involvement of participants in the design or conduct of studies as assessed by criterion L (

| Reflexive thematic analysis
The active process of reflexive thematic analysis produced five significant themes relating to the needs of lymphoma survivors (Table 3). This includes disparity in health service delivery, psychological impact of cancer, impactful and debilitating concerns, the monetary cost of survival and insufficient provision of survivorship information. Study characteristics are outlined in Table A4.

| Disparity in health service delivery
The uncertainty and life transitions in the post-treatment period included what to do now or how to return to normal and receiving guidance or information relevant to this was essential to survivors. 47 need for a new normal. 47,62 Transitions to follow-up care in fragmented health service systems were reported. 5 While survivors felt a need to make sense of the cancer experience, some reported seeing others 'survive and thrive' after cancer as empowering 60 pp. 1470.
A lack of targeted and speciality services for lymphoma contributed to survivor distress. 5,47 For lymphoma survivors, limited financial and psychosocial support was available compared to other cancer groups such as breast cancer. 47 From a US perspective, speciality lymphoma care providers in smaller hometowns were scarce and contributed to negative experiences of diagnosis, including, in some cases, incorrect diagnosis. 5 In addition, travel distance was a barrier to healthcare for some survivors with long commutes and travel costs. 5,48 The diagnosis of haematological malignancy in older persons is frequently delayed due to issues with referrals, general practitioners' limited knowledge of haematological pathologies and complications of comorbidities in masking symptoms. 35 Qualitative reports from participants show an acute awareness of the busy clinical environment and demands on healthcare professionals; this was a barrier to some survivors expressing their needs with healthcare professionals as they did not feel comfortable disturbing staff. 60

| The psychological impact of cancer
The fear of cancer recurrence was a predominant concern reported by lymphoma survivors. 40,59,[61][62][63][64] For some, any physical symptom experienced instilled fear of recurrence between follow-up appointments. A heightened fear was experienced before and during scheduled appointments. 61 Help to manage the fear of recurrence was a frequently endorsed need in reviewed studies. 40,63,64 The fear of recurrence was described as a shared experience of living with uncertainty and fear for some focus group participants (n = 17). 62 However, the degree of fear of recurrence was not different between stages of aggressive NHL. 59 Other means of psychological distress were reported by many lymphoma survivors, including depression, anxiety, and stress. 3,21,41,42,45,63,[65][66][67] Participants with above typical symptoms of depression and stress had statistically significant odds of reporting multiple high-level unmet needs. 21,39 Younger participants reported better physical but worse mental health. 68 The initial delivery of diagnosis required a psychological adjustment that was considered more complex than the physical impact of the disease. 48,60 While some survivors felt their perceived need for help peaked just after being diagnosed, for others, their need for help escalated during cancer recurrence. 48 One study reported the psychosocial impact of body image for this cancer group; female survivors' body image is more impaired and markedly varies from their male counterparts, with more concern relating to their physical appearance than males. 33 Furthermore, an interesting finding from focus groups in the UK was how survivors felt different to other cancer patients. 60 Many lymphoma survivors reported impaired neurocognitive functioning affecting younger survivors of both NHL and HL. 34,55,59,69 Impaired cognitive functioning at diagnosis for NHL survivors was significantly associated with a lack of life purpose in long-term survivors. 59 Almost one-third of participants (n = 523) in a cross-sectional survey indicated a need to avail psychological health care. More than half stated this need was left unmet. 52  Similarly, patients on sick leave during relapse following autologous stem cell transplantation were found to have a poorer prognosis relating to returning to work and a higher rate of disability pension. 54 Lower income was associated with more significant unmet needs relating to expenses for medical and living costs. 44 Furthermore, lymphoma survivors may be immunocompromised, which can be a substantial barrier to returning to work. 61 However, for some survivors, a return to work was seen as a return to normal. 61

| Insufficient provision of survivorship information
Unmet information needs were prevalent in lymphoma survivors from varying countries and research approaches. 43 There were gender differences in the provision of information needs, with males being more likely to report unmet information needs. 52 Men wanted to discuss more than they did, while women managed to discuss the topics they wished to discuss. 51 However, one study found that satisfaction with information provision was relatively good in two-thirds of survivors, with HL the most satisfied (74%). 43 The use of technology was seen as favourable for improved were a prominent concern relating to worries about money and bar- haematological speciality health providers such as general practitioners. 8,35 Yet it is vital to acknowledge the complexities of these issues, which may be multifactorial, involving both patient and health service provider-related problems and solutions. 9 Similar to a systematic review conducted on factors associated with fear of recurrence in cancer patients, with over half of included studies focused on breast cancer, there was an association between physical symptoms for lymphoma survivors and the fear of cancer recurrence. 75 Financial hardship among survivors has been well documented; however, substantial heterogeneity in its prevalence was found by a systematic review of mixed cancer types. 76 For lymphoma, this rapid review found that many survivors are among our workforce internationally, and financial and work-related con- Themes contain textured and nuanced layers, and this review has used them to capture the rich diversity of the needs of lymphoma survivors. The findings of this review extend our current understanding of lymphoma survivors who experience a myriad of unmet needs from diagnosis to survivorship.

| Study limitations
The fundamental limitations of current literature involve the lack of qualitative, mixed methods and longitudinal approaches, with many included studies conducted at single sites, limiting generalisability.
The methodological quality of included articles was high. Yet, key details relating to sociodemographic information, socioeconomic

| Conclusions
Despite advances in the survivorship rates of lymphoma survivors, the treatment of cancer is unfortunately not without consequence. This often contributes to various needs that are frequently long-term.
Lymphoma survivors are largely active in our global workforce yet experience a significant burden of financial and work-related concerns.
They experience disruption to psychosocial wellbeing, including fear of cancer recurrence, fragmented health services and insufficient provi- Open access funding provided by IReL.

CONFLICT OF INTEREST
The authors declare no conflicts of interest.

ETHICAL STATEMENT
Ethical approval was not required for this review.

DATA AVAILABILITY STATEMENT
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Denmark
National registry • Older patients (>55 years) were more likely to return to work compared to younger patients. 12.8 years (SD 5.0)

Arden-
• No gender differences were found in self-reported late effects or perceived vulnerability, however, men with more late effects reported worse psychological HRQoL.

United Kingdom Single site
• Men wished to talk about more topics than they did, while women were able to talk about the topics they wanted.

Beaven 2016 553
Evaluate differences in QoL between incurable indolent lymphoma and potentially cured aggressive NHL.

50%
100% NHL (Mean 61.9, SD 13.5) 10.6 years (SD 6.9) • Aggressive and indolent lymphoma survivors were found to have similar overall QoL, however differences were greater in short-term survivors.

United States
Two sites • Longer-term indolent lymphoma survivors had higher QoL scores than shorter-term survivors.

Unclear
• Baseline severe fatigue was often younger, more often female, and had a higher stage of disease compared to patients without a baseline of severe cancer-related fatigue.
• Five years post-therapy, 84% of survivors without severe fatigue were working or in education, compared to 57% of survivors' experiencing severe fatigue.

Germany Database
Chen 2012

511
Evaluate the disparities in employment and insurance between HL survivors and their non-diagnosed peers.

49.5%
100% HL 16-82 (median 44) Median 15 years (range 5-32) • HL survivors were more likely to report job denial, difficulty obtaining insurance due to medical history, and difficulty changing jobs due to fear of losing insurance.

United States
Single site • Male gender, income, and scarring of the head and neck were associated with job denial (multivariate analysis).
(Continues) BOLAND ET AL. • Worse QoL predictors included: being female, not being in remission at the time of the survey, number of comorbidities, and having a history of relapse.

Germany Two cancer registries
• Compared with the general population, haematology cancer survivors scored significantly lower in functioning and higher in symptom burden.

NR
• Lymphoma survivors were more likely to report post-traumatic stress symptoms (6% vs. 1%) and problems with sexual desire, erection, ejaculation, or vaginal dryness or pain (62% vs. 51%) compared to myeloma survivors.

United States
Single site • Worse mental functioning was associated with younger age and treatment for anxiety, depression, or pain. • Of the HL patients who did not store a sperm sample, the majority (52%) reported that they were not offered the chance to store a sperm sample, whereas among NHL patients most (55%) of those who did not store a sperm sample did not intend to have any children after treatment. • Survivors who: had relocated due to their cancer, had difficulty paying bills, had used up their savings because of cancer, and were classified as having above-normal symptoms of depression and stress had statistically significantly higher odds of reporting seven or more 'high/very high' unmet needs. 1-60 months • 'Dealing with feeling tired' was identified as the highest concern by survivors.

Australia
• Having a personal expense in the last month because of having cancer, younger age at diagnosis, female sex, vocational or other level education, and consulting a health care professional for cancer treatment or concerns about cancer in the last month were associated with multiple areas of need.

NR
• Eighty-five per cent of participants were employed when diagnosed, 77% before high-dose chemotherapy and autologous stem-cell transplantation and 69% at the survey.

Norway
Hospital registry • Employment before HDT-ASCT positively corresponds with a higher probability of employment at survey for a given symptom burden.
(Continues) BOLAND ET AL. of NHL were found to fear the probability of relapse and second malignancy.

South Korea
Single site • More than 65% of survivors thought they did not receive sufficient support from others, and patients who had financial difficulties at diagnosis were more frequently associated with suffering from insufficient support. 3.7 years (SD 2.7)

Keegan
• Two-thirds of survivors were satisfied with the amount of received information, with HL survivors being most satisfied (74%). At least 25% of survivors wanted more information.
• Younger age, having had chemotherapy, having been diagnosed more recently, using the Internet for information, and having no comorbidities were key factors associated with higher perceived levels of information provision.

NR
• The rate of unmet needs was highest for sexual issues, handling medical and living expenses, emotional difficulties, employment, and health insurance.
• Women were more likely to report unmet childcare needs than men; younger individuals were more likely to report needing help with emotional difficulties and family problems, and lower income was related to greater unmet needs for medical and living expenses.

United States
Cancer registry (Continues) BOLAND ET AL.

United States Two cancer registries
• No significant differences were seen between shortterm survivors (2 -4 years post-diagnosis) and long-term survivors (>5 years post-diagnosis).