Whole-slide image analysis of the tumor as a predictor of adverse outcome in patients with advanced-stage classical Hodgkin lymphoma treated with BEACOPP

被引：20

作者：

Jachimowicz, Ron Daniel ^{[1
,2
,3
,4
,5
,7
]}

Pieper, Luise ^{[6
]}

Reinke, Sarah ^{[6
]}

Gontarewicz, Artur ^{[6
]}

Pluetschow, Annette ^{[1
,2
,3
,7
]}

Haverkamp, Heinz ^{[1
,2
,3
,7
]}

Frauenfeld, Leonie ^{[7
]}

Fend, Falko ^{[7
]}

Overkamp, Mathis ^{[7
]}

Jochims, Franziska ^{[6
]}

Thorns, Christoph ^{[8
]}

Hansmann, Martin Leo ^{[9
]}

Moller, Peter ^{[7
,10
]}

Rosenwald, Andreas ^{[11
,12
]}

Stein, Harald ^{[13
]}

Reinhardt, Hans Christian ^{[1
,4
,5
,14
,15
]}

Borchmann, Peter ^{[1
,2
,3
,5
,7
]}

von Tresckow, Bastian ^{[1
,2
,3
,5
,7
]}

Engert, Andreas ^{[1
,2
,3
,5
,7
]}

Klapper, Wolfram ^{[6
]}

机构：

[1] Univ Cologne, Fac Med, Cologne, Germany

[2] Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany

[3] German Hodgkin Study Grp, Cologne, Germany

[4] Univ Hosp Cologne, Else Kroner Forsch Kolleg Clonal Evolut Canc, Cologne, Germany

[5] Univ Hosp Cologne, Ctr Integrated Oncol Aachen Bonn Cologne Dusseldo, Dept Internal Med 1, Cologne, Germany

[6] Univ Kiel, Univ Hosp Schleswig Holstein, Hematopathol Sect, Dept Pathol, Kiel, Germany

[7] Univ Tubingen, Dept Pathol, Tubingen, Germany

[8] Univ Lubeck, Univ Hosp Schleswig Holstein, Dept Pathol, Lubeck, Germany

[9] Univ Hosp Frankfurt, Dept Pathol, Frankfurt, Germany

[10] Univ Hosp Ulm, Dept Pathol, Ulm, Germany

[11] Univ Wurzburg, Inst Pathol, Wurzburg, Germany

[12] Comprehens Canc Ctr Mainfranken, Wurzburg, Germany

[13] Pathodiagnost, Berlin, Germany

[14] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany

[15] Univ Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany

来源：

HAEMATOLOGICA | 2021年 / 106卷 / 06期

关键词：

REED-STERNBERG CELLS; INTERNATIONAL PROGNOSTIC SCORE; CD20; EXPRESSION; B-CELLS; MACROPHAGES; SURVIVAL; CHEMOTHERAPY; MICROENVIRONMENT; CHECKPOINT; REVEALS;

D O I：

10.3324/haematol.2019.243287

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

A subset of patients with advanced-stage classical Hodgkin lymphoma (cHL) relapse or progress following standard treatment. Given their dismal prognosis, identifying this group of patients upfront represents an important medical need. While prior research has identified characteristics of the tumor microenvironment, which are associated with cHL outcomes, biomarkers that are developed and validated in this high-risk group are still lacking. Here, we applied whole-slide image analysis (WSI), a quantitative, large-scale assessment of tumor composition that utilizes conventional histopathology slides. We conducted WSI on pre-treatment biopsies from 340 patients with advanced-stage cHL enrolled in the HD12 and HD15 trials of the German Hodgkin Study Group (GHSG), and tested our results in a validation cohort of 147 advanced-stage cHL patients within the GHSG HD18 trial. All patients were treated with BEACOPP-based regimens. By quantifying T cells, B cells, Hodgkin and Reed-Sternberg cells and macrophages with WSI, 80% of all cells in the tumor tissue were identified. Crucially, low B-cell count was associated with significantly reduced progression-free survival and overall survival, while the content of T cells, macrophages and Hodgkin and Reed-Sternberg cells was not associated with the risk of progression or relapse in the study cohort. We further validated low B-cell content as a prognostic factor for progression-free survival and overall survival in the validation cohort and demonstrated the good inter-observer agreement of WSI. WSI may represent a key tool for risk stratification of advanced-stage cHL and can easily be added to the standard diagnostic histopathology work-up.

引用

页码：1684 / 1692

页数：9

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