The number of extranodal sites assessed by PET/CT scan is a powerful predictor of CNS relapse for patients with diffuse large B-cell lymphoma: An international multicenter study of 1532 patients treated with chemoimmunotherapy

• Published in: European journal of cancer (1990) 2017-04, Vol.75, p.195-203
• Main Authors: El-Galaly, Tarec Christoffer, Villa, Diego, Michaelsen, Thomas Yssing, Hutchings, Martin, Mikhaeel, Nabegh George, Savage, Kerry J, Sehn, Laurie H, Barrington, Sally, Hansen, Jakob W, Smith, Daniel, Rady, Kirsty, Mylam, Karen J, Larsen, Thomas S, Holmberg, Staffan, Juul, Maja B, Cordua, Sabrina, Clausen, Michael R, Jensen, Kristina B, Johnsen, Hans E, Seymour, John F, Connors, Joseph M, de Nully Brown, Peter, Bøgsted, Martin, Cheah, Chan Y
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B-cell lymphoma; Biomarkers; Central nervous system; Central Nervous System Neoplasms - diagnostic imaging; Central Nervous System Neoplasms - prevention & control; Central Nervous System Neoplasms - secondary; CNS prophylaxis; CNS relapse; CNS-IPI; Combined Modality Therapy; Computed tomography; Confidence intervals; Cyclophosphamide - administration & dosage; Diffuse large B-cell lymphoma; Doxorubicin - administration & dosage; Health risks; Hematology, Oncology and Palliative Medicine; Humans; Immunotherapy - methods; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - diagnostic imaging; Lymphoma, Large B-Cell, Diffuse - prevention & control; Male; Mathematical models; Medical databases; Medical prognosis; Middle Aged; Multivariate analysis; Neoplasm Recurrence, Local - diagnostic imaging; Neoplasm Recurrence, Local - prevention & control; Patients; PET/CT; Positron emission; Positron Emission Tomography Computed Tomography; Prediction models; Prednisone - administration & dosage; Prognosis; Retrospective Studies; Risk analysis; Risk Factors; Risk groups; Rituximab; Secondary CNS involvement; Surgical outcomes; Tomography; Treatment Outcome; Uterus; Vincristine - administration & dosage; Young Adult
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2016.12.029

Abstract Purpose Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown. Methods We retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens. Baseline clinicopathologic characteristics, treatments, and outcome data were collected from clinical databases and medical files. We evaluated the association between candidate prognostic factors and modelled different risk models for predicting SCNS. Results Of 1532 patients, 62 (4%) subsequently developed SCNS. By multivariate analysis, disease stage III/IV, elevated serum LDH, kidney/adrenal and uterine/testicular involvement were independently associated with SCNS. There was a strong correlation between absolute number of extranodal sites and risk of SCNS; the 144 patients (9%) with >2 extranodal sites had a 3-year cumulative incidence of SCNS of 15.2% (95% confidence interval [CI] 9.2–21.2%) compared with 2.6% (95% CI 1.7–3.5) among those with ≤2 sites ( P  2 extranodal sites or high-risk disease according to the CNS-IPI should be considered for baseline CNS staging. Clinical risk prediction models suffer from limited positive predictive ability, highlighting the need for more sensitive biomarkers to identify patients at highest risk of this devastating complication.