Prospective Study of 3′-Deoxy-3′-18F-Fluorothymidine PET for early interim response assessment in advanced-stage B-cell lymphoma

Heiko Sch der, Andrew D. Zelenetz, Paul Hamlin, Somali Gavane, Steven Horwitz, Matthew Matasar, Alison Moskowitz, Ariela Noy, Lia Palomba, Carol Portlock, David Straus, Ravinder Grewal, Jocelyn C. Migliacci, Steven M. Larson, Craig Moskowitz

Research output: Contribution to journalArticle

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Abstract

Current clinical and imaging tools remain suboptimal for early assessment of prognosis and treatment response in aggressive lymphomas. PET with 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) can be used to measure tumor cell proliferation and treatment response. In a prospective study in patients with advanced-stage B-cell lymphoma, we investigated the prognostic and predictive value of 18F-FLT PET in comparison to standard imaging with 18F-FDG PET and clinical outcome. Methods: Sixty-five patients were treated with an induction/consolidation regimen consisting of 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) followed by 3 cycles of ICE (ifosfamide, carboplatin, etoposide). 18F-FLT PET was performed at baseline and at interim (iPET) after 1.2 cycles of therapy. 18F-FDG PET was performed at baseline, after cycle 4, and at the end of therapy. The relationship between PET findings, progressionfree survival (PFS) and overall survival (OS) was investigated. Results: With a median follow-up of 51 mo, PFS and OS were 71% and 86%, respectively. 18F-FLT iPET, analyzed visually (using a 5-point score) or semiquantitatively (using SUV and δSUV) predicted both PFS and OS (P < 0.01 for all parameters). Residual 18F-FLT SUVmax on iPET was associated with an inferior PFS (hazard ratio, 1.26, P 5 0.001) and OS (hazard ratio, 1.27, P 5 0.002). When 18F-FDG PET was used, findings in the end of treatment scan were better predictors of PFS and OS than findings on the interim scan. Baseline PET imaging parameters, including SUV, proliferative volume, or metabolic tumor volume, did not correlate with outcome. Conclusion: 18F-FLT PET after 1.2 cycles of chemotherapy predicts PFS and OS, and a negative 18F-FLT iPET result may potentially help design risk-adapted therapies in patients with aggressive lymphomas. In contrast, the positive predictive value of 18F-FLT iPET remains too low to justify changes in patient management. 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Original languageEnglish (US)
Pages (from-to)728-734
Number of pages7
JournalJournal of Nuclear Medicine
Volume57
Issue number5
DOIs
StatePublished - May 1 2016
Externally publishedYes

Fingerprint

B-Cell Lymphoma
Prospective Studies
Survival
Fluorodeoxyglucose F18
alovudine
Lymphoma
Therapeutics
Ifosfamide
Molecular Imaging
Carboplatin
Vincristine
Etoposide
Prednisone
Tumor Burden
Doxorubicin
Cyclophosphamide
Cell Proliferation

Keywords

  • B-cell cell lymphoma
  • FDG PET
  • FLT PET
  • Outcome

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Prospective Study of 3′-Deoxy-3′-18F-Fluorothymidine PET for early interim response assessment in advanced-stage B-cell lymphoma. / Sch der, Heiko; Zelenetz, Andrew D.; Hamlin, Paul; Gavane, Somali; Horwitz, Steven; Matasar, Matthew; Moskowitz, Alison; Noy, Ariela; Palomba, Lia; Portlock, Carol; Straus, David; Grewal, Ravinder; Migliacci, Jocelyn C.; Larson, Steven M.; Moskowitz, Craig.

In: Journal of Nuclear Medicine, Vol. 57, No. 5, 01.05.2016, p. 728-734.

Research output: Contribution to journalArticle

Sch der, H, Zelenetz, AD, Hamlin, P, Gavane, S, Horwitz, S, Matasar, M, Moskowitz, A, Noy, A, Palomba, L, Portlock, C, Straus, D, Grewal, R, Migliacci, JC, Larson, SM & Moskowitz, C 2016, 'Prospective Study of 3′-Deoxy-3′-18F-Fluorothymidine PET for early interim response assessment in advanced-stage B-cell lymphoma', Journal of Nuclear Medicine, vol. 57, no. 5, pp. 728-734. https://doi.org/10.2967/jnumed.115.166769
Sch der, Heiko ; Zelenetz, Andrew D. ; Hamlin, Paul ; Gavane, Somali ; Horwitz, Steven ; Matasar, Matthew ; Moskowitz, Alison ; Noy, Ariela ; Palomba, Lia ; Portlock, Carol ; Straus, David ; Grewal, Ravinder ; Migliacci, Jocelyn C. ; Larson, Steven M. ; Moskowitz, Craig. / Prospective Study of 3′-Deoxy-3′-18F-Fluorothymidine PET for early interim response assessment in advanced-stage B-cell lymphoma. In: Journal of Nuclear Medicine. 2016 ; Vol. 57, No. 5. pp. 728-734.
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abstract = "Current clinical and imaging tools remain suboptimal for early assessment of prognosis and treatment response in aggressive lymphomas. PET with 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) can be used to measure tumor cell proliferation and treatment response. In a prospective study in patients with advanced-stage B-cell lymphoma, we investigated the prognostic and predictive value of 18F-FLT PET in comparison to standard imaging with 18F-FDG PET and clinical outcome. Methods: Sixty-five patients were treated with an induction/consolidation regimen consisting of 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) followed by 3 cycles of ICE (ifosfamide, carboplatin, etoposide). 18F-FLT PET was performed at baseline and at interim (iPET) after 1.2 cycles of therapy. 18F-FDG PET was performed at baseline, after cycle 4, and at the end of therapy. The relationship between PET findings, progressionfree survival (PFS) and overall survival (OS) was investigated. Results: With a median follow-up of 51 mo, PFS and OS were 71{\%} and 86{\%}, respectively. 18F-FLT iPET, analyzed visually (using a 5-point score) or semiquantitatively (using SUV and δSUV) predicted both PFS and OS (P < 0.01 for all parameters). Residual 18F-FLT SUVmax on iPET was associated with an inferior PFS (hazard ratio, 1.26, P 5 0.001) and OS (hazard ratio, 1.27, P 5 0.002). When 18F-FDG PET was used, findings in the end of treatment scan were better predictors of PFS and OS than findings on the interim scan. Baseline PET imaging parameters, including SUV, proliferative volume, or metabolic tumor volume, did not correlate with outcome. Conclusion: 18F-FLT PET after 1.2 cycles of chemotherapy predicts PFS and OS, and a negative 18F-FLT iPET result may potentially help design risk-adapted therapies in patients with aggressive lymphomas. In contrast, the positive predictive value of 18F-FLT iPET remains too low to justify changes in patient management. 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.",
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AU - Sch der, Heiko

AU - Zelenetz, Andrew D.

AU - Hamlin, Paul

AU - Gavane, Somali

AU - Horwitz, Steven

AU - Matasar, Matthew

AU - Moskowitz, Alison

AU - Noy, Ariela

AU - Palomba, Lia

AU - Portlock, Carol

AU - Straus, David

AU - Grewal, Ravinder

AU - Migliacci, Jocelyn C.

AU - Larson, Steven M.

AU - Moskowitz, Craig

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N2 - Current clinical and imaging tools remain suboptimal for early assessment of prognosis and treatment response in aggressive lymphomas. PET with 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) can be used to measure tumor cell proliferation and treatment response. In a prospective study in patients with advanced-stage B-cell lymphoma, we investigated the prognostic and predictive value of 18F-FLT PET in comparison to standard imaging with 18F-FDG PET and clinical outcome. Methods: Sixty-five patients were treated with an induction/consolidation regimen consisting of 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) followed by 3 cycles of ICE (ifosfamide, carboplatin, etoposide). 18F-FLT PET was performed at baseline and at interim (iPET) after 1.2 cycles of therapy. 18F-FDG PET was performed at baseline, after cycle 4, and at the end of therapy. The relationship between PET findings, progressionfree survival (PFS) and overall survival (OS) was investigated. Results: With a median follow-up of 51 mo, PFS and OS were 71% and 86%, respectively. 18F-FLT iPET, analyzed visually (using a 5-point score) or semiquantitatively (using SUV and δSUV) predicted both PFS and OS (P < 0.01 for all parameters). Residual 18F-FLT SUVmax on iPET was associated with an inferior PFS (hazard ratio, 1.26, P 5 0.001) and OS (hazard ratio, 1.27, P 5 0.002). When 18F-FDG PET was used, findings in the end of treatment scan were better predictors of PFS and OS than findings on the interim scan. Baseline PET imaging parameters, including SUV, proliferative volume, or metabolic tumor volume, did not correlate with outcome. Conclusion: 18F-FLT PET after 1.2 cycles of chemotherapy predicts PFS and OS, and a negative 18F-FLT iPET result may potentially help design risk-adapted therapies in patients with aggressive lymphomas. In contrast, the positive predictive value of 18F-FLT iPET remains too low to justify changes in patient management. 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

AB - Current clinical and imaging tools remain suboptimal for early assessment of prognosis and treatment response in aggressive lymphomas. PET with 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) can be used to measure tumor cell proliferation and treatment response. In a prospective study in patients with advanced-stage B-cell lymphoma, we investigated the prognostic and predictive value of 18F-FLT PET in comparison to standard imaging with 18F-FDG PET and clinical outcome. Methods: Sixty-five patients were treated with an induction/consolidation regimen consisting of 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) followed by 3 cycles of ICE (ifosfamide, carboplatin, etoposide). 18F-FLT PET was performed at baseline and at interim (iPET) after 1.2 cycles of therapy. 18F-FDG PET was performed at baseline, after cycle 4, and at the end of therapy. The relationship between PET findings, progressionfree survival (PFS) and overall survival (OS) was investigated. Results: With a median follow-up of 51 mo, PFS and OS were 71% and 86%, respectively. 18F-FLT iPET, analyzed visually (using a 5-point score) or semiquantitatively (using SUV and δSUV) predicted both PFS and OS (P < 0.01 for all parameters). Residual 18F-FLT SUVmax on iPET was associated with an inferior PFS (hazard ratio, 1.26, P 5 0.001) and OS (hazard ratio, 1.27, P 5 0.002). When 18F-FDG PET was used, findings in the end of treatment scan were better predictors of PFS and OS than findings on the interim scan. Baseline PET imaging parameters, including SUV, proliferative volume, or metabolic tumor volume, did not correlate with outcome. Conclusion: 18F-FLT PET after 1.2 cycles of chemotherapy predicts PFS and OS, and a negative 18F-FLT iPET result may potentially help design risk-adapted therapies in patients with aggressive lymphomas. In contrast, the positive predictive value of 18F-FLT iPET remains too low to justify changes in patient management. 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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KW - FDG PET

KW - FLT PET

KW - Outcome

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