The Impact of a Multidisciplinary Clinic on Diagnosis and Management of Patients with Cutaneous T-cell Lymphoma

doi:10.21203/rs.3.rs-4708793/v1

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The Impact of a Multidisciplinary Clinic on Diagnosis and Management of Patients with Cutaneous T-cell Lymphoma

https://doi.org/10.21203/rs.3.rs-4708793/v1

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Multidisciplinary clinics (MDCs) have been shown to improve patient outcomes and reduce disease-specific mortality. This study aims to evaluate the impact of a MDS clinic on diagnosis, management, and clinical outcomes of patients diagnosed with CTCL. A retrospective cohort analysis of a CTCL MDS clinic was conducted between January 2018 to August 2023 at a large academic institution. Patients diagnosed with CTCL with at least one visit to the CTCL MDS clinic were included. Medical records were reviewed for patient demographics, diagnosis change, treatment management, survival outcomes, and clinicopathologic disease characteristics at 6-month intervals. A descriptive analysis was performed. 55 patients were identified (mean age 62.7; 58.1% male; 89.1% White). 80.0% of patients were diagnosed with CTCL, however, 78% were previously diagnosed with other dermatologic conditions. At initial presentation, 20% had a change in diagnosis with 12.7% changing to a benign dermatologic condition. Only 9% of patients had staging prior to initial visit, while majority (62%) received initial staging evaluation during their first visit. At the initial visit, 50.2% had an escalation of treatment, mainly of skin-directed therapy (36.4%). Over 6-month intervals, majority of patients had an escalation of treatment (21.1–51.1%). The modified severity weighted assessment tool (mSWAT) decreased over time (41.8 to 3.5), with many achieving stable disease (18.4–50%). MDS management is highly recommended for patients with CTCL. This study further highlights the important role of a CTCL MDS clinic, specifically in establishing accurate diagnoses, managing appropriate treatments, and stabilizing disease progression.

cutaneous t-cell lymphoma

lymphoma

skin cancer

multidisciplinary clinic

Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma, defined by its manifestations within the skin in the absence of extracutaneous manifestations at diagnosis.¹ The incidence of CTCL is approximately 0.96 per 100,000, with mycosis fungoides (MF) and Sézary Syndrome (SS) subtypes most recognized.² The clinical presentation of CTCL varies significantly and features often overlap with benign inflammatory skin conditions such as atopic dermatitis, psoriasis, and parapsoriasis. Due to the low incidence of CTCL and its shared clinical manifestations with other conditions, diagnosis is challenging. Consequently, diagnosis and treatment of CTCL are often delayed, sometimes greater than four decades, resulting in disease progression and poor patient outcomes.³ Given the considerable diagnostic difficulty, patients with CTCL are likely to benefit from multidisciplinary (MDS) consultation and management.

MDS care has become widely accepted across multiple disciplines. Dermatology MDS clinics, such as combined dermatology-rheumatology clinics, have been shown to improve patient outcomes, raise patient and physician satisfaction, and design effective treatment regimens.⁴ Furthermore, a 2020 systematic review found that caring for patients with dermatologic disease and psychosocial comorbidities in a MDS setting limited inaccurate diagnoses, ineffective treatments, and led to improved patient outcomes.⁵ In addition, MDS clinics have positively impacted patients with cancer leading to decreased time to treatment, accurate staging, improved treatment adherence, and disease-specific survival.^6–9

While many patients with CTCL only experience limited disease confined to the skin, the clinical course of CTCL is unpredictable and those who progress to late-stage disease often require systemic and skin directed therapy from multiple providers including dermatologists, hematologists/oncologists, and radiation oncologists.¹⁰ Although MDS care is recommended,¹¹ few CTCL specific MDS clinics exist. The University of Nebraska Medical Center established a MDS CTCL clinic in 2018 to provide accessible, comprehensive patient-centered care. To assess the impact of our CTCL MDS clinic, a retrospective cohort analysis was conducted to highlight the impact of an MDS clinic on diagnosis, treatment, and outcomes of patients with CTCL.

We conducted a retrospective cohort analysis of the Cutaneous T-cell Lymphoma Multidisciplinary clinic at the University of Nebraska Medical Center, which was reviewed and approved by the University of Nebraska Medical Center Institutional Review Board. Patients diagnosed with CTCL with at least one visit to the CTCL MDS clinic between January 2018 and August 2023 were included in the study. Patients were seen by both an attending dermatologist and medical oncologist with a radiation oncologist in close collaboration as needed. Patients diagnosed with lymphomatoid papulosis were excluded from the study due to its benign clinical course.

The electronic medical records were reviewed for patient demographics, staging, diagnosis change, treatment management, survival outcomes, and clinicopathological disease characteristics at 6-month intervals for 5 years. All patients had an initial visit documented; however, some patients were lost to follow up or did not return every 6 months. If patients had more than one visit within a 6-month time interval, all treatment as well as the highest Modified Severity Weighted Assessment Tool (mSWAT) and LDH was documented. An escalation in treatment was defined as a change or addition of skin directed and/or systemic therapy, while a de-escalation of treatment was defined as decreasing from systemic to skin directed therapy or a decrease in number of total treatment modalities. Skin assessment and response to treatment was assessed with the mSWAT. Treatment response and staging was documented using the definition and criteria from Olsen et al.^12,13 Advanced stage was considered stages IIB through IVB. A descriptive analysis using frequencies and percentages to highlight changes in diagnosis and disease management was performed.

A total of 55 unique patients had an initial visit to the CTCL multidisciplinary clinic, of which the majority were male (58.1%), White (89.1%), and had a mean age of 62.7 (Table 1). 80.0% of patients were previously diagnosed with CTCL before presenting to MDS clinic, however 78% were previously diagnosed with other dermatologic conditions, with dermatitis (56.5%) being the most common followed by psoriasis (23.3%). 20.0% of patients had an initial change in diagnosis, with 12.7% changing to a benign dermatologic condition. Only 9% of patients underwent staging prior to initial CTCL MDS clinic visit, while 62% of patients received initial staging evaluation during their first visit. 36.6% of patients were diagnosed with advanced-stage disease, including 24% with blood involvement. Upon initial visit, 50.2% had an escalation in treatment comprising mostly of skin-directed therapy (36.4%).

Over 6-month intervals, the majority of patients continued to have an escalation of therapy ranging from 21.1–51.1% (Table 2). The modified Severity Weighted Assessment Tool (mSWAT) decreased over 6-month intervals from a mean of 41.8 to 3.5, with most achieving stable disease (18.4–50%). 23.6% patients experienced a median time to large cell transformation of 7.5 months (range 0–38). No visceral metastasis was recorded, although 14.5% had nodal involvement. 12.7% of patients expired during the study, with a median time to death of 12 months (range 4–41).

Herein, we found that our CTCL MDS clinic positively impacts patient care, specifically in establishing accurate diagnoses, treatment management, and stabilizing disease progression. Diagnosing CTCL is challenging, and many patients often experience a delay in diagnosis. In a multicenter study evaluating disease course of CTCL, patients with skin lesions related to CTCL experienced an average delay of diagnosis of two years, with some exceeding 50 years before receiving a definitive diagnosis.¹⁴ In our study, 78% of patients were previously diagnosed with a benign dermatologic condition, and 13% of patients diagnosed with CTCL received a benign diagnostic change after presenting to CTCL MDS clinic, which further highlights the challenges of distinguishing this disease. Minimizing delays in CTCL diagnosis is essential for patient outcomes, as those with early-stage disease, specifically stage IA, experience similar survival outcomes to age-matched healthy controls,¹⁵ while those with late-stage disease have overall poor survival outcomes.¹⁶ However, on the contrary, receiving a false-positive cancer diagnosis can lead to unnecessary testing, additional medical costs, and significant emotional burden.¹⁷ Because CTCL diagnosis can be challenging, prompt referral to a dermatologist or MDS CTCL clinic may improve diagnostic accuracy and decrease delays in diagnosis and management.

In our study, only 9% patients had complete staging before presenting to CTCL MDS, while 62% were evaluated for stage during their first visit. Dermatologists play a pivotal role in staging, specifically for assessing T stage, which is solely based on skin evaluation.¹⁸ Staging is one of the most important aspects for determining treatment strategies, as early-stage disease is largely managed by skin directed therapy. Even in late-stage disease, skin-directed therapy in combination with systemic therapy can improve symptoms and skin tumor burden.¹⁹ At initial presentation to the UNMC MDS CTCL clinic, 53% of patients underwent an escalation in therapy, with the majority comprising of skin directed therapy (36%). As time progressed, majority of patients had no subsequent change in treatment regimen as most achieved stable, partial, or complete response to therapy.

Skin directed therapy remains first-line treatment for those with early-stage disease, while systemic therapy may be initiated or added in patients with late-stage, refractory, or if relapse of disease occurs.¹⁹ While some guidelines do exist, there is a lack of randomized controlled trials assessing therapeutic strategies in patients with CTCL.²⁰ Many treatment options with similar efficacy exist for skin-directed and systemic treatment.²¹ Selection of appropriate therapy will differ across providers and will often depend on provider preference, clinical presentation, and availability of treatment.¹⁹ Utilizing the expertise of a dermatologist in conjunction with oncology and radiation oncology in MDS setting may better optimize patient treatment strategies and outcomes.

While many dermatologists primarily manage early stage CTCL with skin directed therapy, they play an active role in managing and guiding treatment decisions in late stage or refractory disease. Specifically, a dermatologist’s unique expertise in skin manifestation can help identify early cutaneous disease progression and differentiate adverse skin reactions, which may mitigate early termination of treatment or premature escalation of therapy.²² A MDS care model has been highly emphasized for managing patients with CTCL, largely due to the logistically complex shift from skin directed therapy under the supervision of a dermatologist, to oncology-driven care.²³ Centralizing patient care allows specialists to communicate directly and make prompt treatment decisions while ensuring shared understanding of all involved parties.²³

Patients with CTCL should be seen regularly once diagnosis is established to monitor for signs of disease progression. The ESMO guidelines recommend that follow-up be individualized depending on clinical scenarios. Those with indolent subtypes of CTCL or stable disease can be seen every 6–12 months, while those with active or progressive disease are often seen every 4–6 weeks.¹¹ Some patients with CTCL may undergo a process of large-cell transformation (LCT), which is characterized by an aggressive disease course and is associated with poor survival.^24,25 LCT is often difficult to diagnose, as clinical presentation can vary from a single papule emerging in a pre-existing plaque to multiple standalone nodules and tumors with ulceration.²⁵ In our MDS CTCL clinic, 24% of patients were diagnosed with LCT. Although diagnosis is made histologically, dermatologists play a crucial role in identifying early signs of LCT to facilitate further work up. Furthermore, regular follow-up with a MDS CTCL clinic may mitigate progression of disease with early identification of LCT and initiation of aggressive treatment as needed.

The use and benefit of a disease-specific MDS has been well documented across multiple medical specialties. Specifically, MDS cancer clinics have most notably improved disease-specific survival.^6,26–28 While we were unable to assess disease-specific survival due to low sample size, patients from our MDS CTCL clinic had a decreasing trend in average mSWAT (41.8 to 3.5), with many patients achieving at least partial response to treatment without disease progression. Reasons for improved clinical outcomes associated with MDS specialty clinics may be multifactorial. In a previous study, treatment adherence to NCCN guidelines of patients with prostate cancer was improved after implementing a prostate MDS clinic, while multiple studies have shown cancer specific MDS clinics decrease time to treatment initiation and improve treatment adherence.^7,9,26,29,30 In addition, patient satisfaction tends to be improved with MDS clinics, as many reported reductions in number of office visits while experiencing an improved understanding of their condition and treatment regimen.³¹

This is one of the first studies to report on the impact of a MDS CTCL clinic. Like previous disease-specific studies, we found that MDS management positively impacts diagnosis and management of patients with CTCL as well as minimizes disease progression. Limitations of our study include a small sample size and a relatively homogenous cohort, which may limit generalizability of our findings. Nonetheless, MDS care should be accessible to all patients diagnosed with CTCL, and this study further underscores the importance of a MDS CTCL clinic to improve patient-centered care.

Conflict of Interest

The authors have no conflicts of interest to disclose.

Funding

none

Ethical Approval
Approved by UNMC IRB #0577-23-EP

Author Contribution

S.T and M.A. wrote the main manuscript. S.T. and M.T. performed data collection.M.S. was the lead investigator.All authors reviewed and edited the manuscript.

Data Availability

The participants of this study did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research supporting data is not available.

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Table 1. Clinical characteristics of patients in a CTCL MDS clinic
Characteristic	Total, No. (%)
Age, mean (SD) (n=55)	62.7 (15.7)
Sex (n=55)
Male	32 (58.1)
Female	23 (41.8)
Race (n=55)
White	49 (89.1)
Other¹	6 (10.9)
Ethnicity, Non-Hispanic (n=55)	55 (100)
Previous Dermatology Visit (n=53)	49 (92.5)
Previously Diagnosed with CTCL (n=55)	44 (80)
Other Previous Diagnoses² (n=55)	43 (78)
Dermatitis	20 (56.5)
Psoriasis	10 (23.3)
None	11 (25.6)
Other³	8 (18.6)
Diagnosis Change (n=55)	11 (20)
To other CTCL subtype	4 (7.3)
From CTCL to other⁴	7 (12.7)
New Diagnosis	9 (16.4)
CTCL Subtypes (n=53)
Mycosis Fungoides	37 (69.8)
Sezary Syndrome	7 (13.2)
CD4+ Lymphoproliferative Disorder	2 (3.8)
Anaplastic Large Cell Lymphoma	1 (1.9)
Subcutaneous Panniculitis-Like	1 (1.9)
Tumor Board (n=55)	8 (14.5)
Stage (n=41)
T Stage
T1/T2	28 (68.3)
T3/T4	13 (31.7)
N Stage
N1/N1	4 (9.8)
N3/N4	6 (14.6)
M Stage	-
B Stage
B1	4 (9.8)
B2	9 (22.0)
Stage Changes (n=41)
Up Stage	4 (9.8)
Down Stage	1 (2.1)
Large Cell Transformation (n=55)	13 (23.6)
Time to Large Cell Transformation, median months, range	7.5, 0-38
Metastasis (n=55)
Nodal Involvement	8 (14.5)
Visceral	0
Deceased (n=55)	7 (12.7)
Time to Death, month, range	12, (4-41)
¹Black (n=5), American Indian and Alaskan Native (n=1); ²Pityriasis rubra pilaris, tinea, tinea versicolor, rosacea, peripheral T-cell lymphoma, atypical lymphocytic infiltrate, keratosis pilaris; ³Can have more than one; ⁴Pseudolymphoma, CD30+ cutaneous proliferation, dermatitis, psoriasiform dermatitis, solar lentigo CTCL, Cutaneous T-cell lymphoma; MDS, multidisciplinary, SD, standard deviation

Table 2. Changes in disease progression and management
	Initial (n=55)	0-6 m (n=47)	6-12 m (n=38)	12-18 m (n=31)	18-24 m (n=19)	+24 m (n=32)
Treatment
No Change	22 (40)	17 (36.2)	15 (39.5)	13 (41.9)	11 (57.9)	19 (59.4)
Escalated Treatment¹	29 (52.7)	24 (51.1)	11 (28.9)	10 (32.3)	4 (21.1)	8 (25)
SDT	20 (36.4)	10 (21.3)	2 (5.3)	6 (19.4)	1 (5.3)	4 (12.5)
Systemic	5 (9.1)	9 (19.1)	4 (10.5)	0 (0)	2 (10.5)	4 (12.5)
SDT+Systemic	4 (7.3)	5 (10.6)	5 (13.2)	4 (12.9)	1 (5.3)	0 (0)
De-Escalated Treatment	5 (9.1)	3 (6.4)	6 (15.8)	4 (12.9)	2 (10.5)	5 (25.6)
Systemic to SDT	5 (9.1)	3 (6.4)	2 (5.3)	2 (6.5)	1 (5.3)	1 (3.1)
Decrease SDT	0 (0)	0 (0)	4 (10.5)	2 (6.5)	1 (5.3)	4 (12.5)
Unknown	0 (0)	3 (6.4)	6 (15.8)	4 (12.9)	2 (10.5)	1 (3.1)
mSWAT	41.8 (40.0)	29.1 (29.1)	19.2 (25.9)	21.4 (34.0)	16.5 (26.9)	3.5 (15.6)
Unknown	17 (30.9)	14 (29.8)	11 (28.9)	11 (35.5)	5 (29.4)	11 (34.4)
Treatment Response²
Stable	-	19 (40.4)	7 (18.4)	7 (22.6)	9 (47.4)	16 (50)
Partial Response	-	5 (10.6)	5 (13.2)	5 (16.1)	2 (10.5)	4 (12.5)
Complete Response	-	2 (4.3)	2 (5.3)	(6.5)	2 (10.5)	0 (0)
Progression	-	6 (12.8)	3 (7.9)	3 (9.7)	1 (5.3)	3 (9.4)
Relapse	-	1 (2.1)	1 (2.6)	2 (6.5)	0 (0)	0 (0)
Unknown	-	14 (29.8)	20 (52.6)	12 (38.7)	5 (26.3)	9 (28.1)
Flow Cytometry
Positive	7 (12.7)	4 (8.5)	3 (7.9)	2 (6.5)	1 (5.3)	2 (6.3)
Negative	20 (36.4)	6 (12.8)	7 (18.4)	4 (12.9)	4 (21.1)	3 (9.4)
Unknown	28 (50.9)	38 (80.9)	28 (73.7)	25 (80.7)	14 (73.7)	27 (84.4)
LDH, mean (SD) use	222.8 (87.5)	219 (82.0)	203.1 (81.6)	211.7 (57.9)	205.8 (81.1)	221.5 (97.3)
Unknown	39 (70.9)	32 (74.4)	23 (60.5)	22 (71.0)	14 (73.7)	26 (81.3)
¹Added or changed skin directed/systemic therapy SDT, skin directed therapy; mSWAT, modified severity weighted assessment tool

No competing interests reported.

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You are reading this latest preprint version

The Impact of a Multidisciplinary Clinic on Diagnosis and Management of Patients with Cutaneous T-cell Lymphoma

Status:

Version 1

Abstract

Introduction

Methods

Results

Discussion

Declarations

Conflict of Interest

Funding

Ethical Approval
Approved by UNMC IRB #0577-23-EP

Author Contribution

Data Availability

References

Tables

Additional Declarations

Status:

Version 1

The Impact of a Multidisciplinary Clinic on Diagnosis and Management of Patients with Cutaneous T-cell Lymphoma

Status:

Version 1

Abstract

Introduction

Methods

Results

Discussion

Declarations

Conflict of Interest

Funding

Ethical Approval Approved by UNMC IRB #0577-23-EP

Author Contribution

Data Availability

References

Tables

Additional Declarations

Status:

Version 1

Ethical Approval
Approved by UNMC IRB #0577-23-EP