TY - JOUR
T1 - 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
T2 - An international multicenter study of 1532 patients treated with chemoimmunotherapy
AU - El-Galaly, Tarec Christoffer
AU - Villa, Diego
AU - Michaelsen, Thomas Yssing
AU - Hutchings, Martin
AU - Mikhaeel, Nabegh George
AU - Savage, Kerry J.
AU - Sehn, Laurie H.
AU - Barrington, Sally
AU - Hansen, Jakob W.
AU - Smith, Daniel
AU - Rady, Kirsty
AU - Mylam, Karen J.
AU - Larsen, Thomas S.
AU - Holmberg, Staffan
AU - Juul, Maja B.
AU - Cordua, Sabrina
AU - Clausen, Michael R.
AU - Jensen, Kristina B.
AU - Johnsen, Hans E.
AU - Seymour, John F.
AU - Connors, Joseph M.
AU - de Nully Brown, Peter
AU - Bøgsted, Martin
AU - Cheah, Chan Y.
PY - 2017
Y1 - 2017
N2 - 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 < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values. Conclusions Patients with >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.
AB - 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 < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values. Conclusions Patients with >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.
KW - CNS prophylaxis
KW - CNS relapse
KW - CNS-IPI
KW - Diffuse large B-cell lymphoma
KW - PET/CT
KW - Prognosis
KW - Secondary CNS involvement
U2 - 10.1016/j.ejca.2016.12.029
DO - 10.1016/j.ejca.2016.12.029
M3 - Journal article
C2 - 28237865
AN - SCOPUS:85013673875
SN - 0959-8049
VL - 75
SP - 195
EP - 203
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -