AUTHORS
Muhammad Saad Hamid, MD, Ashley McCook, MPH2, Jeffrey Switchenko3, Neha Mehta-Shah, MD, MSCI4, Neha Akkad, MD5, Luis Malpica, MD6, Kelsey Kille, MD7, Danielle Wallace, MD8, Evelyn Hastings Orlando, MD9, Jia Ruan, MD, PhD10, Saja Kadhim Asakrah,, MD11, Melissa Larson, MS12, Georgios N Pongas13, James R. Cerhan, MD, PhD14, Christopher R. Flowers Jr, MD, MS15, Eric Mou, MD16, Nora Bennani, MD17, Pamela Allen, MD18
AFFILIATIONS
1 Winship Cancer Institute of Emory University, Atlanta, Georgia, United States
2 Winship Cancer Institute of Emory University, Atlanta, Georgia, United States
3 Winship Cancer Institute of Emory University, Atlanta, Georgia, United States
4 Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States
5 The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
6 The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
7 University of Rochester, Rochester, New York, United States
8 University of Rochester, Rochester, New York, United States
9 Weill Cornell Medicine, New York, New York, United States
10 Weill Cornell Medicine, New York, New York, United States
11 Winship Cancer Institute of Emory University, Atlanta, Georgia, United States
12 Mayo Clinic, Rochester, Minnesota, United States
13 Sylvester Comprehensive Cancer Center, Miami, Florida, United States
14 Mayo Clinic, Rochester, Minnesota, United States
15 The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
16 University of Iowa, Iowa City, Iowa, United States
17 Mayo Clinic, Rochester, Minnesota, United States
18 Winship Cancer Institute of Emory University, Atlanta, Georgia, United States
ABSTRACT
Introduction: Accurate TNMB staging is central to prognosis and treatment selection in mycosis fungoides (MF) and Sézary syndrome (SS), yet current ISCL/EORTC guidelines offer limited specificity on how staging should be established across compartments. How these practices are applied in across academic institutions and the degree to inter-institutional variation that exists, remains poorly characterized.
Methods: We used the prospective, multicenter LEO-MER cohort (NCT02736357) to characterize diagnostic and staging practices among adults with confirmed MF/SS across 8 US academic centers, describing skin, blood, and node-compartment staging patterns (including clonality testing methodology and pathologic nodal evaluation), stratified by early-stage (ES, IA-IIA) vs advanced-stage (AS, IIB-IVB) disease. A structured site survey characterized flow cytometry panel composition and TCR methodology. Categorical comparisons used chi-square/Fisher's exact tests.
Results: Among 177 patients (pts) with confirmed MF/SS, 111 (62.7%) had ES and 66 (37.3%) had AS disease at diagnosis. Median age was 64 years (range 18-88), with 58.2% (n=103) male, 69.5% (n=123) White, 16.4% (n=29) Black, and 2.8% (n=5) Asian, and elevated LDH at diagnosis was present in 37.1% (n=52) of pts.
Skin (T) stage among ES pts included T1 in 52.3% (n=58) and T2 in 47.7% (n=53), with patch-vs-plaque subclassification undocumented in 18.9% (n=21) of cases. Skin involvement among AS pts included T1 in 1.5% (n=1), T2 in 7.6% (n=5), T3 in 30.3% (n=20), and T4/erythroderma in 60.6% (n=40), differing significantly from ES (p<0.001). Skin T-cell clonality testing was performed in 46.8% (n=52) of ES and 62.1% (n=41) of AS pts. Among those tested, a clonal population was identified in 75.0% (n=39) of ES and 73.2% (n=30) of AS pts, respectively (p=1.00).
Blood involvement differed significantly by stage (p<0.001), with B0 in 73.0% (n=81) of ES vs 27.3% (n=18) of AS, B1 in 7.2% (n=8) vs 13.6% (n=9), B2 in 0% (n=0) vs 48.5% (n=32), and Bx in 19.8% (n=22) vs 10.6% (n=7). Molecular blood clonality testing was performed in 57.7% (n=64) of ES and 69.7% (n=46) of AS pts; among those tested, a clonal population was identified in 34.4% (n=22) and 76.1% (n=35), respectively (p<0.001). Skin-to-blood clonality matching was attempted in only 28.8% (n=32) of ES and 36.4% (n=24) of AS pts and confirmed in just 12.6% (n=14) and 24.2% (n=16), respectively (p=0.062).
Nodal stage also differed significantly by stage (p<0.001), with N0 in 80.2% (n=89) of ES vs 22.7% (n=15) of AS, N1 in 4.5% (n=5) vs 15.2% (n=10), N2 in 2.7% (n=3) vs 6.1% (n=4), N3 in 0 vs 28.8% (n=19), and Nx in 12.6% (n=14) vs 27.3% (n=18). Nodal biopsy was rare in ES (6.4%, n=7) but occurred in 51.5% (n=34) of AS pts (p<0.001), most often excisional (45.5%, n=15), then core (27.3%, n=9) and FNA (21.2%, n=7) (p=0.19). Of 34 biopsied AS pts, FCM data were available for 28 (75%, n=21 positive); molecular clonality testing was performed in only 35.7% (n=10) of these, confirming a concordant clonal result in 5 pts.
At highest follow-up stage, pathologic nodal evaluation was obtained in only 21.9% (7/32) of pts with Nx at diagnosis, with 5 progressing to higher stage without pathologic confirmation. Blood status was reassessed in 65.5% (19/29) of pts with Bx (18 reclassified B0, 1 B1).
No single marker reached full 8-of-8 site consensus on our survey, including core T-cell lineage markers: CD3 and CD8 were included at 7 of 8 sites, CD4 and CD7 at 6 of 8, and CD2 at 5 of 8. CTCL-relevant markers were even less consistent with CD26 at 6 of 8, CD200 at 3 of 8, TRBC1 at 2 of 8, and TCR-gamma/delta at only 1 of 8. TCR clonality methodology included the BIOMED-2 Invivoscribe assay (paired with gamma PCR, beta PCR, or NGS) at 4 of 8 sites, TCR-gamma PCR alone at 2 of 8, and NGS-based sequencing at 3 of 8.
Conclusions: Many advanced-stage patients had unassessed nodal or blood compartments. Providers may reasonably proceed to treatment when nodal involvement is radiographically evident or testing for clonality would not change management. Flow cytometry panels varied across sites, with no single marker used universally, and skin-blood clonality matching was performed infrequently. These findings suggest an opportunity to further standardize staging practices and improve prognostic accuracy in MF/SS.
DISCLOSURES
Muhammad Saad Hamid, MD: No relevant conflicts of interest to declare.