Current measures are not sufficient: an interview-based qualitative assessment of quality of life in cutaneous T-cell lymphoma

Abstract

Background:

Cutaneous T-cell lymphoma (CTCL) negatively impacts quality of life (QoL), but existing QoL questionnaires may not comprehensively reflect patients’ experience.

Objectives:

To identify the aspects of QoL that are most meaningful to patients with CTCL and to evaluate existing QoL instruments in this context.

Methods:

Semi-structured interviews were conducted using purposive sampling of CTCL patients between May and June 2019. Data were analyzed by an inductive thematic approach using Dedoose Version 8.0.35.

Results:

One-on-one interviews were completed by 18 patients (median age 62 (IQR 18); 39% advanced stage [IIB-IV]), lasting a median of 43 minutes. Itch was the most common clinical symptom reported (16/18 patients), followed by pain (12/18); skin breaks (11/18); and skin flaking (10/18). Eleven patients reported that their symptoms interfered with sleep, which impacted daily functioning. Patients also noted a lack of understanding of the disease in the community and felt uncertain (12/18), depressed (11/18), suicidal (4/18), and hopeless (9/18). Nearly all patients (17/18) reported a sense of “otherness” (not feeling “normal” or “like themselves”), and most patients (16/18) specifically mentioned concern about their physical appearance. Patients also noted substantial treatment burden. Salient patient concerns, including individual clinical symptoms, concern about appearance, and problems with sleep, were not adequately or consistently represented in generic, skin-specific, or CTCL-specific QoL measures.

Conclusions:

Incorporating these concerns and priorities that distinguish CTCL patients from other patient populations will be of paramount importance in developing a comprehensive CTCL-specific measure of QoL that adequately captures patients’ experience.

Introduction

Cutaneous T-cell lymphoma (CTCL) is a rare subtype of non-Hodgkin lymphoma involving malignant clonal T cells that home to the skin (1). Mycosis fungoides (MF) and Sézary syndrome (SS), the most prevalent forms of CTCL, can have variable clinical presentations ranging from plaques and patches in early-stage disease to tumors, ulcerations, and erythroderma in advanced-stage disease. The incidence of MF is approximately 6 cases per million per year, comprising 4 percent of all cases of non-Hodgkin lymphoma (2-4). CTCL disproportionately affects African Americans, the elderly, and males, with a 2:1 male:female ratio (4-6). The lesions associated with MF/SS can be disfiguring, pruritic, and painful, substantially impacting patients’ psychosocial well-being, daily functioning, and overall quality of life (QoL) (7-10).

Despite empirical observations among healthcare professionals who work with patients with MF/SS, systematic reviews have identified fewer than 15 studies to date with the primary objective of assessing QoL in the CTCL population (11, 12). Additionally, these studies tended to be limited by their utilization of generic QoL instruments. While generic measures such as the Health Utilities Index (HUI3) and RAND 36-Item Short-Form Health Survey (SF-36) provide critical insight into the overall impact of the disease, they are designed to evaluate general aspects of QoL across a diverse range of diseases and, thus, are limited in their capacity to capture constructs that are more specific to CTCL (13, 14). Similarly, skin-specific instruments such as the Skindex-29 and Dermatology Life Quality Index (DLQI), though used widely across dermatologic conditions, are limited in their ability to capture oncologic and systemic aspects of CTCL (15-17). Furthermore, existing instruments do not correlate well with clinical disease burden as determined by body surface area (18). The need for a CTCL-specific QoL measure led to the creation of the MF/SS-CTCL QoL instrument, developed based on 3 interviews with clinical leaders and 10 interviews with patients with self-reported diagnoses of MF or SS (19). However, evaluation of advanced-stage patients was limited, and the final instrument therefore omitted certain aspects of QoL noted to be meaningful in previous studies, including problems with sleep (8, 19, 20).

In other disease areas, including atopic dermatitis and psoriasis, there is a concerted effort to identify core patient outcome domains, including QoL, and make recommendations on the instruments that should be used within these domains (21-24). However, there is limited parallel information on the instruments that should be used to assess QoL in CTCL. Some qualitative research studies have shed light on the marked impact of CTCL on patients’ physical, psychological, and social wellbeing (8, 20). However, there is still potential to gain a stronger understanding of the overall impact of MF/SS at all stages through one-on-one interviews. Thus, in this qualitative study, we explore the impact of CTCL on patients’ daily lives by allowing them to describe their experiences in their own words. The objective of this study is to identify the aspects of QoL that are most meaningful to CTCL patients across various stages of the disease in order to further elucidate the components that are most essential in assessing QoL in CTCL and to evaluate existing QoL instruments, including the new disease-specific MF/SS-CTCL QoL, in this context.

Methods:

Approval for this study was obtained from the Institutional Review Board at Washington University School of Medicine in St. Louis, Missouri. Participants with either MF or SS were recruited from a multidisciplinary CTCL clinic affiliated with a National Cancer Institute (NCI)-designated comprehensive cancer center. The clinical multidisciplinary team includes dermatology, clinical oncology, clinical psychology, and a specialist pharmacist. To ensure representation of the full spectrum of QoL burden in CTCL, patients were selectively recruited by stage and symptom severity. Symptom severity was determined using patients’ most recent Skindex-29 scores.

Patients with early- or late-stage MF or SS completed a one-on-one, semi-structured interview with a medical researcher trained in qualitative methods (CH) between May 2019 and June 2019. Enrollment was continued until the research team (TB, CH, AM) agreed that thematic saturation was achieved (i.e., no new themes were emerging from the data). Interview questions were developed using topics identified empirically from patient conversations during clinic visits and from our review of the literature (8, 9, 11, 20, 25). Most interviews were conducted over the phone, though some patients chose to be interviewed in a private room in the hospital. All interviews were audio recorded, deidentified, and transcribed verbatim for analysis. Data were coded using Dedoose Version 8.0.35. We used inductive thematic analysis to analyze the coded interview data (26), and frequency analysis to report the number of patients mentioning specific clinical symptoms.

Inductive thematic analysis:

Interviews were coded using a three-step process involving open coding, axial coding, and selective coding (26, 27). During open coding, interview transcripts were each reviewed by two researchers (TB and CH), who developed an initial codebook consisting of descriptive codes (categories) that fit the ideas espoused in the interviews (27, 28). TB and CH individually coded a randomly selected interview transcript line-by-line using this codebook, then met with a third qualitative studies researcher (OS) in order to reconcile differences in coding and revise the codebook accordingly. TB and CH then applied the revised codebook to a second randomly selected interview transcript, and this iterative revision process was repeated until no major coding discrepancies remained between the two coders. The final codebook was reviewed and approved by a fourth researcher with extensive clinical experience with the CTCL population (AM). One coder (TB) then systematically applied the final codebook to all interview transcripts in the dataset, while the other coder (CH) re-coded a random sample of 3 of 18 of the transcripts to confirm continued consensus. Through this method, the qualitative data were able to be summarized and interpreted based on the frequency with which each code was applicable. Clean verbatim quotations from and reference to specific patients are denoted by patient number (e.g., P1, P2, etc.) with indication of patient sex. Bracketed comments within quotations were added by the authors for clarification.

Comparison to existing QoL instruments:

The most frequent and salient patient concerns identified from the current interviews were then examined for their presence in a selection of QoL instruments, including the SF-36, HUI3, DLQI, Skindex-29, and MF/SS-CTCL QoL (15, 17, 19, 29, 30). The SF-36 is the most widely used QoL measure in research to date; the HUI3 provides additional insight into the economic impact of varying degrees of QoL impairment; the DLQI is the most widely used QoL instrument in dermatology; and the Skindex-29 is often used to assess QoL among patients with cutaneous lymphoma, as it incorporates additional psychological aspects of QoL not addressed in the DLQI (16, 18, 25, 31-33). The final developed codebook was applied to these existing QoL instruments, with coding performed by TB and code assignment confirmed by AM. Each topic of interest was documented for inclusion within an instrument if the instrument was coded at least once for that topic.

Results:

Demographic and clinical characteristics

Eighteen patients completed an interview. Interviews lasted for a median of 43 minutes, totaling 804 minutes of audio recordings and 506 transcript pages. Among the 11 participants with early-stage CTCL (stages IA-IIA), 7 reported mild-to-moderate symptoms, while 4 reported severe symptoms based on the Skindex-29. Seven interviews were conducted with patients with advanced-stage disease (stages IIB-IV). Patients with advanced-stage disease were not stratified by symptom severity due to limited sample size. The median age was 62 (range 26-80, IQR 18), 10 (55.5%) of the 18 patients were female, and 13 patients (72.2%) were white (Table 1). These demographic characteristics were largely representative of the overall CTCL patient population seen at Washington University (18).

Table 1.

Baseline characteristics of the sample.

Characteristic		N (%)
Gender
	Male	8 (44.44)
	Female	10 (55.56)
Age, median (IQR)		61.64 (18)
Race
	Non-Hispanic White	13 (72.22)
	Non-Hispanic Black	5 (27.78)
Stage*
	IA	7 (38.89)
	IB	4 (22.22)
	IIB	1 (5.56)
	III	4 (22.22)
	IV	2 (11.11)

^*

Stages of cutaneous T-cell lymphoma:

• Stage I: Patch or plaque-stage disease.

  • IA: Less than 10% of the skin is affected.
  • IB: 10-80% of the skin is affected.
• Stage II: Some lymph nodes may be enlarged. There may be abnormal lymphocytes in the lymph nodes. There may be tumors (>1 cm) on the skin.
• Stage III: More than 80% of the skin is affected (erythroderma).
• Stage IV: Abnormal lymphocytes have spread to the lymph nodes, blood, and/or other organs.

Major themes

The encompassing themes emerging from the data indicated the pervasive nature of CTCL on patients’ lives. Broad themes pertained to clinical symptoms (Table 2), psychological and social functioning, and treatment burden. Specific themes and subthemes are described below, with additional quotations presented in Table 3.

Table 2.

Frequency of clinical symptoms.

Symptom	Number of patients (Total N = 18)
Itch	16
Pain	12
Fatigue	12
Sleep	11
Skin fissuring, sores, and lacerations	11
Skin flaking	10
Skin redness	8
Heat regulation	6
Skin dryness	6
Constitutional symptoms	3
Hair loss	2
Concentration	2
Weight loss	2
Eyes tearing up	1
Wrinkled skin	1

Table 3.

Patient quotations.

Key Theme: Clinical symptoms and associated concerns
Pruritus	“It’s like if you went camping for 2 weeks and you were around a lot of mosquitoes and weeds and wasn’t able to bathe, that’s what it felt like to me. Like you had a 100-fold more poison ivy than a normal person would have.” (P12, female) “I mean, the itching is, like, your back, your neck, your head, your arms, your leg, your—I mean, it's just like—to describe it, just say, "fire ants."…Fire ants all over your body… you find anything to scrape, to scrape your arm, your legs, your body with.” (P13, male)
Pain	“…It’s too painful for me to be on my feet… the pain is kind of, uh, sharp… It’s almost like a spear or something.” (P4, female) “I was in pain all of the time because my skin always felt like somebody was striking matches on it.” (P9, female)
Skin breaks (fissuring, lacerations, sores), often causing pain	“I get my spots [and] they start to open and crack and pus. And they are very uncomfortable. I mean, they hurt when they get to that point because they're infected. And if I bump it on something it hurts incredibly. It's like hitting your funny bone times 100. It's so very painful.” (P5, female) “…If that area gets really dry and cracked to where you got splits…your earlobes will feel like they’re splitting off, and they feel like paper cuts… it’s a non-stopping, constant like burning, just like you would slice yourself with a piece of paper… and then you got the other places, like an ulcerated tumor area… you hit it on something, and then it’s pretty agonizing, a stabbing type of pain.” (P8, male)
Insomnia, secondary to other clinical symptoms and worry about disease	“[CTCL] doesn’t let you sleep at night because you’re just constantly fixated on what’s going wrong, what could go wrong, how it affects the people that are close to you, all those kinds of things.” (P7, male) “Middle of the night, I wake up itching, so it’s like every day, all day… Last night, I woke up, like, five times itching.” (P14, female) “And then the pain, I wake up in the middle of night sometimes with the pain… It feels like needles sticking in your body… And sometimes it's so bad, like I said, I wake up with it.” (P10, female)
Skin flaking	“I can’t get certain jobs because I have to wear a hat. And I flake so much, I can’t be around food. So, yeah, jobs are kind of limited.” (P14, female) “Literally, in the bathroom every morning, [my wife] would sweep up a—I'm not lying—a cupful of skin…I have piles of skin on the carpet, on the floor of the car… 'Cause there'd just be so much skin sloughing off. Dust everywhere.” (P16, male)
Key Theme: Psychological and social functioning
Subtheme: Lack of understanding and awareness in the community
Lack of understanding in community compared to other diseases	“You tell people you have cancer, they think you - you’ve got a tumor so that an operation will fix it.” (P4, female) “If you say skin cancer, people have other things and not the thing that you have…And so people will go, ‘Oh, is it like melanoma?’ No, not like that, you know.” (P6, female)
Lack of media coverage	“There’s not commercials for it…it’s kind of like a mystery disease.” (P6, female) “You're always seeing advertisements on TV for this kind of cancer, that kind of cancer, and you go, okay, but I've got cancer, and they don't talk about any of my stuff.” (P9, female)
Misconception as contagious	“…People thought I had chicken pox… I had to have documentation that my skin issues were not contagious…other coaches and teams were afraid that they were gonna get something.” (P5, female) “They might think you kind of have some – something that's catching or whatever.” (P17, male)
Subtheme: Self-image and concern about appearance
Concern about appearance and awareness of scrutiny	“I had a procedure done… and I’m in the wheelchair, and [this man] said, “Oh, you were in the hospital for your face”… it was pointed out to me… I mean, I had a surgery that was a lot more extensive than this… then it was like, oh, thanks, if I don’t have enough pain with this, then you have to point out my face.” (P2, female) “You know they’re detecting, and they’re looking at everything that’s going on… I feel like what a leper must’ve felt like” (P3, male) “I realized that I was the person that people were trying not to look at, but everybody was looking at… you recognized right away that people were trying not to look you in the face, you know? And at the same time, you’d turn your head and everybody’d be looking at you.” (P4, female)
Isolation	“‘Cause when you first find out you have what's basically called an orphan disease, it makes you feel like an orphan… [like] you're the only person in the world who has this problem… It's like you don't have a mommy and a daddy, and you don't have any siblings, and there you are, all alone, and you have to rely on yourself.” (P9, female) “Nobody really wants to hug anymore. You don’t have even… the feeling of people wanting to hug you… my family doesn’t want to touch me now.” (P10, female)
“Otherness”	“The emotional part is extremely there because you—you’re just not yourself.” (P1, male) “Yeah, it feels like it's either something wrong with you or something…I mean, I guess I never had that feeling before.” (P10, female) “I have to deal with just thinking I'm different from everybody else.” (P12, female)
Subtheme: Depression, hopelessness, uncertainty
Depression	“Six months after I was diagnosed I went to my primary care provider and was put on Zoloft because I was so upset about the diagnosis and then the domino effect of the rest of my life… it totally just kind of wrecked our little dream life that we were having.” (P5, female) “I’m on anti-depressant medicine for that…I see a psychiatrist…[for] depression…Some days, I have bad days.” (P15, female)
Hopelessness	“I really lost my bearings, I think. It was like I didn’t know what to do… it was all pretty much finished, and you might as well just sit around and wait to die.” (P7, male) “This is really life-changing, not just having this but dealing with it…Every day you wake up and you think, oh, maybe this'll be a better day, and it's not. But you try to go on, and some days you forget about it, and all of a sudden you look down and you see flaking everywhere and you're like, oh great, still there.” (P10, female) “It was just impossible to find joy each day…because as soon as something good would happen, you’d somehow be reminded of this, and you’d be taken right back down again.” (P18, male)
Uncertainty	“I wouldn’t say that it’s front and center, but there’s always a lingering thought that, you know, what if it advances.” (P6, female) “[CTCL] gets you thinking about your mortality. Is this it? Or is this gonna go into something else? And that lingers to this day… Is it suddenly gonna turn a corner and suddenly gonna get bad in some way, shape, or form?” (P18, male)
Key Theme: Treatment burden
Side effects	“Right, the laser, and then that's when I'm like, yeah, I don't think we'll be doing laser anymore…boy, it just burned the crap out of my arm.” (P11, female) “There have been medical – I guess, more internal side effects like my cholesterol…going through the roof and stuff like that. Now I'm on more medication just to manage that…’cause now I've got to take medication to manage my thyroid…I've got to take medications to manage cholesterol.” (P17, male)
Logistical concerns associated with therapy	“You kind of miss out on things… social things with other people. [And] date night was always Friday night for my husband and myself. But when I was at three times a week where I would go Monday, Wednesday, and Friday… you’d have to change your life a little bit to accommodate the treatment… you have to do everything else around it.” (P6, female) “I miss days [of work] all the time… right now I’m doing light treatments, so I got those three times a week, and every other week I got infusions and doctors’ visits, so that’s a good half a day there.” (P8, male)
Financial cost	“When you're on a fixed income…the added expense, where I was driving three days a week from where I lived to where I get my treatments, and it's 40 miles one way. That's 80 miles round trip, where you do that three times a week. The wear and tear on your car, the added expense for gas… it's just all the little things that goes along with [treatment] that adds up.” (P3, male) “I’m sure you know insurance doesn’t pay for everything, and it’s quite expensive. On top of that, every time you come down and see a doctor it’s considered a specialty visit, you gotta $80 co-pay. Sometimes when am doing light treatments, which I am, they want an $80 co-pay three times a week, and then you top it off with seeing two doctors that same week…You know, it’s 80 times five. I mean, nobody’s going to be able to do that unless you’re rich… So, yeah, the medical bills pile up. You try to pay a little bit here and there, but it’s a never-ending battle. You never get caught up and never can.” (P8, male) “No individual can afford this, even—I've got good insurance, but even with that…. Now that I'm down to just two pills a day, it's around $12,000 a month, but back when I was taking nine pills a day, it was more around 45 or $50,000 a month.” (P9, female)

Patient quotations provided are clean verbatim.

I. Clinical symptoms and associated concerns

Patients reported pervasive clinical symptoms, with the most common complaints being itch, pain, fatigue, skin fissures and sores, and skin flaking. Patients were also bothered by skin redness and poor temperature regulation, with some patients describing excessive heat retention due to inability to sweat and others noting excessive heat loss (Table 2).

Sixteen patients reported experiencing pruritus, with severe psychological consequences, including frustration, depression, and suicidality. One patient described his hopelessness attributed to refractory pruritus: “There’ve been times you have thoughts in your head, oh, just pour some gasoline on myself and burn myself up. Maybe the itch’ll stop…What [do] I have to do? Blow my brains out in order [for it] to stop?” (P13, male).

Many patients also reported pain associated with their disease, which affected the way that they interacted with the world (“I had a very effervescent personality. That seems to be clouded by the pain that I have to go through in order to see clear” [P1, male]) as well as their ability to perform activities of daily living. Many patients attributed their pain specifically to skin breaks, including skin fissuring, lacerations, and sores, which detracted from their mobility, ability to wear clothing of their choice, and interpersonal interactions. In one patient’s words, “I had better manners than to run around with open sores oozing around for other people to see” (P9, female).

Skin flaking was also associated with impairments in social functioning, particularly as it contributed to patients’ feelings of humiliation and the perception of being scrutinized by others. Managing this symptom was particularly effortful and time-consuming, with routines involving frequent bathing, applying topical therapies, wearing additional clothing, and adjusting clothing to expose as little skin as possible (for example, by tucking pants into socks).

Eleven patients reported that their symptoms interfered with sleep, which impacted their QoL and functioning in other realms. Patients reported difficulty falling and staying asleep due to itch, pain, and discomfort, as well as worrying about their disease.

Twelve patients reported fatigue, with lack of energy attributed to the disease itself, poor sleep, emotional exhaustion, and side effects of treatment. Lack of energy prevented patients from accomplishing tasks at work and at home. Patients also reported inability to concentrate secondary to fatigue, itch, or psychological distractions.

II. Psychological and social functioning

A. Lack of understanding and awareness

Thirteen patients mentioned delays in appropriate diagnosis, with most of these patients reporting that their skin disease and clinical symptoms were initially mistaken for psoriasis or eczema. Additionally, constitutional symptoms of CTCL, particularly fatigue, were often mistaken for other systemic diseases, with patients being worked up for thyroid disease and celiac disease, among others. Most patients were relieved when they received a diagnosis, as many had seen multiple doctors without resolution or improvement. One patient described feeling like a hypochondriac and believed that receiving the appropriate diagnosis was necessary affirmation that it “wasn’t all in my head” (P9, female).

Even after receiving a correct diagnosis of CTCL, the rarity and lack of public understanding of the disease were frustrating to many patients. Patients often struggled to explain CTCL to friends and family members and found that there were few appropriate resources available online or in print. Several patients mentioned the impact of media coverage on public perception and normalization of other diseases and were frustrated by the lack of media attention to CTCL. They found that describing their disease as a cancer or a skin cancer led others to draw comparisons to more familiar malignancies with distinct clinical features and courses, such as breast cancer or melanoma. Due to this lack of public understanding, patients often opted to avoid talking about their disease altogether.

When interacting with others, some patients faced the assumption that their rash represented a contagious condition such as chicken pox or even leprosy. Patients often had to correct or accommodate this misperception, going as far as to obtain documented physician approval to participate in contact sports, for example.

B. Self-image and concern about appearance

Sixteen patients reported significant concern about their appearance, with 10 patients specifying that they felt self-conscious and embarrassed. The visibility of CTCL subjected patients to scrutiny, curiosity and ridicule, “‘cause even strangers felt, like, yeah, they can just ask, “Hey, what happened to your arm?’” (P1, male). Patients were acutely aware of the way they were perceived, with one patient describing feeling like a “leper” (P3, male). As a result, patients often refrained from participating in normal daily activities that would require going out in public. Patients described feelings of physical and social isolation due to self-consciousness and the belief that no one could understand what they were going through.

Patients felt that the disease affected not only the way others viewed them, but also the way they viewed themselves. Seventeen patients noted a feeling of “otherness,” referring to the perception that they were different than others or different than their own “normal” selves in irrevocable ways. Conversely, some patients noted that successful treatment allowed them to get back to their “old” or “normal” self.

C. Depression, hopelessness, and uncertainty

Eleven patients reported sadness or depression related to their disease, and 4 patients reported suicidal ideation. Additionally, 9 patients had experienced hopelessness related to their disease, particularly related to the pervasiveness of their clinical symptoms.

Patients also reported significant distress associated with uncertainty regarding their disease course and prognosis. Even patients who were clinically improving reported worrying that they would take a turn for the worse without warning. The lack of certainty around the effectiveness of a particular therapy for an individual patient – though not dissimilar from other diseases – was a particular source of stress for patients with this rare condition, as there were few online and written resources available to help them understand what to expect. Uncertainty also contributed to patients’ frustration and difficulty in explaining their treatment course to others. One patient compared her experience with treatment in CTCL to her perception of the certainty in treatment of other cancers, in which “you’re gonna do like six chemo treatments… and after that you’ll be better,” whereas with CTCL, “this [treatment] doesn’t work and that [treatment] doesn’t work…[and] people don’t understand” (P10, female).

III. Treatment burden

The burden of treatment stemmed from side effects as well as financial cost, issues with transportation and scheduling, and insurance concerns.

A. Side effects

Patients reported treatment-associated symptoms including skin burning and redness, burning eyes, fatigue, nausea and vomiting, fertility problems, vision changes, hair loss, pain, and general constitutional symptoms. Some patients developed new chronic medical conditions as a result of therapy, including secondary diabetes and peripheral neuropathy. One patient noted that he would value his QoL over trying to cure his CTCL if side effects of therapy were too severe: “If you’re just feeling like you have the flu, aching all over, high fever, I mean, who wants to do anything when you’re like that?…If there’s a medication that causes symptoms like that, even if it’s working for the disease, I would value my quality of life better than, or more than, trying to cure the disease at that point” (P8, male).

B. Financial cost and logistical burden

The financial burden of treatment manifested itself not only in the cost of therapy, which was substantial, but also in the logistical burden and added expense of traveling to clinic, particularly for therapies such as narrow-band UVB (light therapy) that required patients to return to clinic up to three times per week. The logistics of traveling to and from the clinic, including paying for gas, standard wear and tear to the car, and navigating traffic, were not always stressful individually but added to the worry associated with side effects of therapy and the disease itself. The frequency of therapy also interfered with patients’ work and social lives and required that patients change their schedules to accommodate regular medical appointments. One patient explained his decision to buy a home light therapy unit despite the substantial cost: “I was like, ‘Do I want to spend $6,000 on something that I may not be using very much?’ And, I mean, initially, before I knew how burdensome the travel was I actually thought, ‘Well, it’s probably not worth it.’ But, of course, once I realized how much effort and stress goes into the travel thing, then the home unit really looks a lot better” (P17, male). Patients who required intravenous therapies noted that infusions, compared to oral medications, were particularly burdensome, as they required full days at the hospital.

Though infusions were covered by Medicare, oral medications were only covered under Medicare Part D, which was not accessible to all patients. Several patients described the distress associated with fighting with insurance companies for coverage of needed therapy. However, patients who were still working noted that they would not have been able to afford their therapy without insurance benefits from work; one patient reported choosing to stay at the same job solely to maintain his insurance benefits.

IV. Comparison to other QoL instruments

None of the existing QoL questionnaires examined, including 2 generic instruments, 2 skin-specific instruments, and a disease-specific MF/SS-CTCL instrument, measured all of the specific patient concerns identified in our patient interviews (Table 4) (13-15, 17, 19). Moreover, several symptoms and concerns of the patients we interviewed were assessed in none or only one of these QoL instruments, including insomnia; skin flaking and skin breaks; social stigma due to lack of public understanding; “otherness,” and hopelessness.

Table 4.

Patient concerns identified by our patients as addressed in existing quality of life instruments.

	HUI3	SF-36	Skindex	DLQI	MF/SS- CTCL
Itch			•	•
Pain	•	•	•	•
Fatigue		•	•		•
Sleep			•
Skin breaks (fissuring, sores, lacerations)
Skin flaking
Lack of understanding in community					•
Concern about appearance			•	•
Isolation	•	•	•	•	•
“Otherness”		•
Depression	•	•	•		•
Hopelessness					•
Uncertainty			•		•
Treatment burden			•	•	•

Quality of life instruments assessed included the Health Utilities Index Mark 3 (HUI3), RAND 36-Item Short Form Health Survey (SF-36), Skindex-29 (Skindex), Dermatology Life Quality Index (DLQI), and the MF/SS-CTCL QoL (MF/SS-CTCL) (13-15, 17, 19).

Discussion

This study corroborates the results of several previous studies that reported poor QoL in patients with CTCL and provides more comprehensive insight into the burden of patients’ experiences living with CTCL (7, 9, 18, 25, 31, 34, 35). Faced with a rare and multifaceted disorder with features of malignancy, chronic disease, and highly visible, inflammatory dermatoses, CTCL patients experience not only debilitating symptoms of their disease, but also prognostic fears, social stigmatization, and financial burden (7-9, 25). Every patient interviewed in this qualitative study detailed the myriad ways in which CTCL had impacted their lives, with varying degrees of disruption. However, several common themes emerged from these narratives, including various clinical symptoms that impacted their daily lives and ability to engage in “normal” role functioning; the psychosocial impact of these symptoms and the disease overall; and salient treatment burden.

Consistent with previous studies, patients emphasized the pervasive and interminable nature of their symptoms, particularly itch (8, 20). They also reported insomnia, resulting in fatigue and lack of productivity. Patients reported feeling depressed, hopeless, and self-conscious about their appearance, with corresponding decrements in their social functioning and ability to participate in daily activities. Furthermore, they described substantial treatment burden, involving financial cost and insurance battles, logistical challenges associated with transportation and scheduling, and side effects of therapy.

There are multiple aspects of QoL that are not adequately represented in existing QoL instruments, and patient concerns do not map consistently to a single measurement tool, including the recently developed MF/SS-CTCL instrument (Table 4). Limitations in the development of the MF/SS-CTCL included significant volunteer bias and measurement bias and lack of inclusion of patients with advanced-stage disease in both development and validation.

Patients were recruited from PatientsLikeMe, a Web-based patient network, precluding the inclusion of individuals without access to the Internet and potentially biasing towards patients who are more engaged in their health and more willing to share their health information. All clinical information, including stage and disease subtype (MF versus SS) was self-reported and was not verified by a licensed medical professional. No patients with stage III or stage IV disease were included in the qualitative study leading to survey development, and most patients who participated in validation of the instrument reported stage I disease.

Advantages of our study include representation of patients at all stages of disease (Table 1); interviews were continued until no new ideas or themes were being generated among patients with early-stage or advanced-stage disease. Additionally, all clinical information was confirmed by a physician, minimizing reporting bias. Moving forward, incorporating these findings that distinguish CTCL patients from other patient populations will be paramount in developing a comprehensive disease-specific instrument that adequately captures their illness experience. As in other disease areas such as atopic dermatitis and psoriasis, identifying the most appropriate patient-reported outcome instruments is important to ensure standardization in clinical trials and to establish standards of care in clinical practice for patients with CTCL (21-24).

Additionally, this study highlights the need for integration of mental health services into the multidisciplinary care of patients with CTCL in order to better address issues of self-image, social isolation, and psychological distress.

Finally, the cost of care for patients should be re-conceptualized to include not only the direct cost of therapy, but also the indirect costs of loss of productivity at work and home. Consideration of these indirect costs should not only influence therapeutic decision-making but also play a role in patient advocacy for grants and other financial support for patients with CTCL.

Limitations of this study include the inherent bias involved in interview-based studies, with a small sample size receiving care at a single academic institution, though many of our findings confirm reports from previous qualitative studies performed at other institutions (8, 20). Similar to other qualitative research studies, our findings may not be generalizable to other cancer-patient populations or to other CTCL patients receiving treatment at hospitals that are not affiliated with an NCI-designated comprehensive cancer center. Similarly, some subthemes, particularly the lack of media coverage surrounding CTCL and financial implications of the disease, may be specific to patients in the United States. However, though these subthemes may not be included in a generalizable, international CTCL-specific measure, they should remain important considerations when treating these patients. Additionally, all qualitative studies are inherently subjective. However, we minimized the potential for inconsistent data collection by using a formal interview guide and the same interviewer for all participants. Multiple researchers were involved in shaping the codebook used in data analysis, and final analysis was performed by a different member of the research team than the original interviewer to minimize bias and subjectivity and increase reliability in our interpretation of results. In addition, we triangulated our findings with the literature, finding that the patient concerns described in our study have also been identified in previous qualitative studies among patients with MF/SS (8, 20). These concerns included individual clinical symptoms, particularly skin flaking and skin breaks; problems with sleep; concern about appearance; lack of public understanding and resulting stigmatization; hopelessness; and expensive, time-consuming therapies.

Work is underway to incorporate these findings in the development of a more comprehensive, disease-specific QoL instrument for patients with CTCL. We plan to validate this new questionnaire in a larger multi-site study of CTCL patients.

Conclusion

CTCL is associated with impaired QoL. Semi-structured interviews with 18 patients with MF or SS revealed that CTCL has a pervasive impact on patients’ psychosocial and physical wellbeing due to embarrassment and stigmatization, pruritus and pain, insomnia and fatigue, side effects of treatment, and the expensive and time-consuming nature of therapy. Many disease-specific QoL concerns are not currently represented in existing QoL instruments, including generic and skin-specific measures as well as a CTCL-specific measure. Incorporating these unique concerns, including specific symptoms, problems with sleep, and concern about appearance, will be of paramount importance in developing a comprehensive disease-specific QoL instrument that fully captures the experience of patients with CTCL.

• Cutaneous T-cell lymphoma (CTCL) negatively impacts quality of life (QoL).

• Our findings demonstrate that existing QoL instruments, including an instrument specific to CTCL, do not adequately reflect patient concerns.

• Incorporating these unique concerns, including specific symptoms, problems with sleep, and concern about appearance, will be of paramount importance in developing a comprehensive disease-specific QoL instrument for patients with CTCL.