Multi-institutional Investigation: Circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam radiation in mycosis fungoides

Yi An, Wen Jiang, Therese Y. Andraos, Jay P. Reddy, Zeinab Abou Yehia, Shane Lloyd, Madeleine Duvic, Neil M. D'Souza, Sarah A. Milgrom, Chelsea C. Pinnix, Yasuhiro Oki, Grace L. Smith, Lynn D. Wilson, Bouthaina S. Dabaja

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1 Scopus citations

Abstract

Background and purpose: A lower proportion of CD8+ tumor infiltrating lymphocytes in mycosis fungoides (MF) patients is associated with worse survival. However, it is not known whether circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam therapy (TSEBT). Methods and materials: We identified 126 MF patients treated with TSEBT from 2001 to 20014 at two high-volume academic centers. Circulating CD4:CD8 ratio was obtained within 1 week before TSEBT. TSEBT was delivered with 6-9mEV electrons with low (12 Gy) or conventional (≥12 Gy) doses. Treatment response was assessed with the modified Severity Weighted Assessment Tool (mSWAT). Post-treatment mSWAT decrease of ≥75% was classified as near complete response (CR) while mSWAT decrease of <75% was considered partial response (PR). Receiver operating characteristic analysis determined an optimal CD4:CD8 threshold value to predict TSEBT response in the derivation cohort and was applied to an external validation cohort. Results: 71.4% and 28.6% of patients achieved CR and PR after TSEBT. Higher CD4:CD8 ratio predicted poorer response: median CD4:CD8 in patients with PR vs. CR was 4.84 vs. 1.97 (p = 0.002). A threshold CD4:CD8 of 4.42 optimally discriminated in the discovery cohort patients with PR vs. XR (sensitivity 90%, specificity 59%, area under curve (AUC) = 0.71; p = 0.002). Within an independent test cohort (n = 32), 73.9% of patients with CD4:CD8 <4.42 achieved CR vs. 33.3% of those with CD4:CD8 ≥4.42 (p = 0.033). Among all patients with CD4:CD8 <4.42 (n = 73), 74% achieved CR with low-dose TSEBT vs. 93% with conventional dose TSEBT (p = 0.02). On multivariable logistic regression, CD4:CD8 remained a significant independent predictor of TSEBT response in all patients (OR = 0.107, 95% CI 0.395–0.290, p < 0.001). Conclusion: Peripheral blood CD4:CD8 ratio was a significant independent predictor of TSEBT response of MF patients as validated in an independent cohort at separate academic center. The potential for CD4:CD8 ratio as a biomarker to inform radiation treatment dosing warrants further investigation.

Original languageEnglish (US)
Pages (from-to)88-92
Number of pages5
JournalRadiotherapy and Oncology
Volume131
DOIs
StatePublished - Feb 2019
Externally publishedYes

Keywords

  • Biomarker
  • Mycoses fungoides
  • Total skin electron therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

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    An, Y., Jiang, W., Andraos, T. Y., Reddy, J. P., Yehia, Z. A., Lloyd, S., Duvic, M., D'Souza, N. M., Milgrom, S. A., Pinnix, C. C., Oki, Y., Smith, G. L., Wilson, L. D., & Dabaja, B. S. (2019). Multi-institutional Investigation: Circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam radiation in mycosis fungoides. Radiotherapy and Oncology, 131, 88-92. https://doi.org/10.1016/j.radonc.2018.12.003