Intravenous but not intrathecal central nervous system-directed chemotherapy improves survival in patients with testicular diffuse large B-cell lymphoma

S Mannisto; P Vähämurto; M Pollari; M R Clausen; S Jyrkkiö; P-L Kellokumpu-Lehtinen; P Kovanen; M-L Karjalainen-Lindsberg; F d'Amore; S Leppä

doi:10.1016/j.ejca.2019.04.004

Intravenous but not intrathecal central nervous system-directed chemotherapy improves survival in patients with testicular diffuse large B-cell lymphoma

Eur J Cancer. 2019 Jul:115:27-36. doi: 10.1016/j.ejca.2019.04.004. Epub 2019 May 10.

Authors

S Mannisto¹, P Vähämurto², M Pollari³, M R Clausen⁴, S Jyrkkiö⁵, P-L Kellokumpu-Lehtinen⁶, P Kovanen⁷, M-L Karjalainen-Lindsberg⁷, F d'Amore⁴, S Leppä⁸

Affiliations

¹ Research Program Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Oncology, Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
² Research Program Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
³ Research Program Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Oncology, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
⁴ Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
⁵ Department of Oncology and Radiotherapy, Turku University Central Hospital, Turku, Finland.
⁶ Department of Oncology, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
⁷ Department of Pathology, Helsinki University Hospital, Helsinki, Finland.
⁸ Research Program Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Oncology, Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland. Electronic address: sirpa.leppa@helsinki.fi.

PMID: 31082690
DOI: 10.1016/j.ejca.2019.04.004

Abstract

Background: Testicular lymphoma is a rare malignancy affecting mainly elderly men, the majority representing diffuse large B-cell lymphoma (DLBCL). Its relapse rate is higher than that of nodal DLBCL, often affecting the central nervous system (CNS) with dismal prognosis.

Patients and methods: We searched for patients with testicular DLBCL (T-DLBCL) involvement from the pathology databases of Southern Finland University Hospitals and the Danish Lymphoma Registry. Clinical information was collected, and outcomes between treatment modalities were evaluated. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods.

Results: We identified 235 patients; of whom, 192 were treated with curative anthracycline-based chemotherapy. Full survival data were available for 189 patients. In univariate analysis, intravenous CNS-directed chemotherapy, and irradiation or orchiectomy of the contralateral testis translated into favourable PFS, DSS and OS, particularly among the elderly patients (each p ≤ 0.023). Intrathecal chemotherapy had no impact outcome. In multivariate analyses, the advantage of intravenous CNS-directed chemotherapy (hazard ration [HR] for OS, 0.419; 95% confidence interval [CI], 0.256-0.686; p = 0.001) and prophylactic treatment of contralateral testis (HR for OS, 0.514; 95% CI, 0.338-0.782; p = 0.002) was maintained. Rituximab improved survival only among high-risk patients (International Prognostic Index≥3, p = 0.019). The cumulative risk of CNS progression was 8.4% and did not differ between treatment modalities.

Conclusion: The results support the use of CNS-directed chemotherapy and prophylactic treatment of the contralateral testis in patients with T-DLBCL involvement. Survival benefit appears resulting from better control of systemic disease rather than prevention of CNS progression.

Keywords: CNS-directed therapy; Primary testicular lymphoma; Prophylactic testicular irradiation; Rituximab; Survival.

Publication types

Comparative Study
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Central Nervous System Neoplasms / mortality
Central Nervous System Neoplasms / prevention & control*
Central Nervous System Neoplasms / secondary
Databases, Factual
Denmark
Disease Progression
Finland
Humans
Infusions, Intravenous
Infusions, Spinal
Lymphoma, Large B-Cell, Diffuse / drug therapy*
Lymphoma, Large B-Cell, Diffuse / mortality
Lymphoma, Large B-Cell, Diffuse / pathology
Lymphoma, Large B-Cell, Diffuse / radiotherapy
Male
Middle Aged
Orchiectomy
Progression-Free Survival
Registries
Risk Assessment
Risk Factors
Testicular Neoplasms / drug therapy*
Testicular Neoplasms / mortality
Testicular Neoplasms / pathology
Testicular Neoplasms / radiotherapy
Time Factors