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

Tarec Christoffer El-Galaly; Diego Villa; Thomas Yssing Michaelsen; Martin Hutchings; Nabegh George Mikhaeel; Kerry J. Savage; Laurie H. Sehn; Sally Barrington; Jakob W. Hansen; Daniel Smith; Kirsty Rady; Karen J. Mylam; Thomas S. Larsen; Staffan Holmberg; Maja B. Juul; Sabrina Cordua; Michael R. Clausen; Kristina B. Jensen; Hans E. Johnsen; John F. Seymour; Joseph M. Connors; Peter de Nully Brown; Martin Bøgsted; Chan Y. Cheah

doi:10.1016/j.ejca.2016.12.029

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

Tarec Christoffer El-Galaly^*, Diego Villa, Thomas Yssing Michaelsen, Martin Hutchings, Nabegh George Mikhaeel, Kerry J. Savage, Laurie H. Sehn, Sally Barrington, Jakob W. Hansen, Daniel Smith, Kirsty Rady, Karen J. Mylam, Thomas S. Larsen, Staffan Holmberg, Maja B. Juul, Sabrina Cordua, Michael R. Clausen, Kristina B. Jensen, Hans E. Johnsen, John F. SeymourJoseph M. Connors, Peter de Nully Brown, Martin Bøgsted, Chan Y. Cheah

^*Corresponding author for this work

Department of Clinical Medicine

34 Citations (Scopus)

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 < 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.

Original language	English
Journal	European Journal of Cancer
Volume	75
Pages (from-to)	195-203
ISSN	0959-8049
DOIs	https://doi.org/10.1016/j.ejca.2016.12.029
Publication status	Published - 2017

Keywords

CNS prophylaxis
CNS relapse
CNS-IPI
Diffuse large B-cell lymphoma
PET/CT
Prognosis
Secondary CNS involvement

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El-Galaly, T. C., Villa, D., Michaelsen, T. Y., Hutchings, M., Mikhaeel, N. G., Savage, K. J., Sehn, L. H., Barrington, S., Hansen, J. W., Smith, D., Rady, K., Mylam, K. J., Larsen, T. S., Holmberg, S., Juul, M. B., Cordua, S., Clausen, M. R., Jensen, K. B., Johnsen, H. E., ... Cheah, C. Y. (2017). 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. European Journal of Cancer, 75, 195-203. https://doi.org/10.1016/j.ejca.2016.12.029

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. / El-Galaly, Tarec Christoffer; Villa, Diego; Michaelsen, Thomas Yssing et al.
In: European Journal of Cancer, Vol. 75, 2017, p. 195-203.

Research output: Contribution to journal › Journal article › Research › peer-review

El-Galaly, TC, Villa, D, Michaelsen, TY, Hutchings, M, Mikhaeel, NG, Savage, KJ, Sehn, LH, Barrington, S, Hansen, JW, Smith, D, Rady, K, Mylam, KJ, Larsen, TS, Holmberg, S, Juul, MB, Cordua, S, Clausen, MR, Jensen, KB, Johnsen, HE, Seymour, JF, Connors, JM, de Nully Brown, P, Bøgsted, M & Cheah, CY 2017, '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', European Journal of Cancer, vol. 75, pp. 195-203. https://doi.org/10.1016/j.ejca.2016.12.029

El-Galaly TC, Villa D, Michaelsen TY, Hutchings M, Mikhaeel NG, Savage KJ et al. 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. European Journal of Cancer. 2017;75:195-203. doi: 10.1016/j.ejca.2016.12.029

El-Galaly, Tarec Christoffer ; Villa, Diego ; Michaelsen, Thomas Yssing et al. / 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. In: European Journal of Cancer. 2017 ; Vol. 75. pp. 195-203.

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title = "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",

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 < 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.",

keywords = "CNS prophylaxis, CNS relapse, CNS-IPI, Diffuse large B-cell lymphoma, PET/CT, Prognosis, Secondary CNS involvement",

author = "El-Galaly, {Tarec Christoffer} and Diego Villa and Michaelsen, {Thomas Yssing} and Martin Hutchings and Mikhaeel, {Nabegh George} and Savage, {Kerry J.} and Sehn, {Laurie H.} and Sally Barrington and Hansen, {Jakob W.} and Daniel Smith and Kirsty Rady and Mylam, {Karen J.} and Larsen, {Thomas S.} and Staffan Holmberg and Juul, {Maja B.} and Sabrina Cordua and Clausen, {Michael R.} and Jensen, {Kristina B.} and Johnsen, {Hans E.} and Seymour, {John F.} and Connors, {Joseph M.} and {de Nully Brown}, Peter and Martin B{\o}gsted and Cheah, {Chan Y.}",

year = "2017",

doi = "10.1016/j.ejca.2016.12.029",

language = "English",

volume = "75",

pages = "195--203",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Pergamon",

}

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 -