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Clinical Cancer Research

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Cancer Therapy: Clinical

Immunochemotherapy with Intensive Consolidation for Primary CNS Lymphoma: A Pilot Study and Prognostic Assessment by Diffusion-Weighted MRI

Matthew J. Wieduwilt, Francisco Valles, Samar Issa, Caroline M. Behler, James Hwang, Michael McDermott, Patrick Treseler, Joan O'Brien, Marc A. Shuman, Soonmee Cha, Lloyd E. Damon and James L. Rubenstein
Matthew J. Wieduwilt
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Francisco Valles
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Samar Issa
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Caroline M. Behler
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James Hwang
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Michael McDermott
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Patrick Treseler
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Joan O'Brien
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Marc A. Shuman
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Soonmee Cha
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Lloyd E. Damon
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James L. Rubenstein
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DOI: 10.1158/1078-0432.CCR-11-0625 Published February 2012
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Abstract

Purpose: We evaluated a novel therapy for primary central nervous system lymphoma (PCNSL) with induction immunochemotherapy with high-dose methotrexate, temozolomide, and rituximab (MT-R) followed by intensive consolidation with infusional etoposide and high-dose cytarabine (EA). In addition, we evaluated the prognostic value of the minimum apparent diffusion coefficient (ADCmin) derived from diffusion-weighted MRI (DW-MRI) in patients treated with this regimen.

Experimental Design: Thirty-one patients (median age, 61 years; median Karnofsky performance score, 60) received induction with methotrexate every 14 days for 8 planned cycles. Rituximab was administered the first 6 cycles and temozolomide administered on odd-numbered cycles. Patients with responsive or stable central nervous system (CNS) disease received EA consolidation. Pretreatment DW-MRI was used to calculate the ADCmin of contrast-enhancing lesions.

Results: The complete response rate for MT-R induction was 52%. At a median follow-up of 79 months, the 2-year progression-free and overall survival were 45% and 58%, respectively. For patients receiving EA consolidation, the 2-year progression-free and overall survival were 78% and 93%, respectively. EA consolidation was also effective in an additional 3 patients who presented with synchronous CNS and systemic lymphoma. Tumor ADCmin less than 384 × 10–6 mm2/s was significantly associated with shorter progression-free and overall survival.

Conclusions: MT-R induction was effective and well tolerated. MT-R followed by EA consolidation yielded progression-free and overall survival outcomes comparable to regimens with chemotherapy followed by whole-brain radiotherapy consolidation but without evidence of neurotoxicity. Tumor ADCmin derived from DW-MRI provided better prognostic information for PCNSL patients treated with the MTR-EA regimen than established clinical risk scores. Clin Cancer Res; 18(4); 1146–55. ©2012 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

  • Received March 15, 2011.
  • Revision received November 18, 2011.
  • Accepted December 22, 2011.
  • ©2012 American Association for Cancer Research.
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Clinical Cancer Research: 18 (4)
February 2012
Volume 18, Issue 4
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Immunochemotherapy with Intensive Consolidation for Primary CNS Lymphoma: A Pilot Study and Prognostic Assessment by Diffusion-Weighted MRI
Matthew J. Wieduwilt, Francisco Valles, Samar Issa, Caroline M. Behler, James Hwang, Michael McDermott, Patrick Treseler, Joan O'Brien, Marc A. Shuman, Soonmee Cha, Lloyd E. Damon and James L. Rubenstein
Clin Cancer Res February 15 2012 (18) (4) 1146-1155; DOI: 10.1158/1078-0432.CCR-11-0625

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Immunochemotherapy with Intensive Consolidation for Primary CNS Lymphoma: A Pilot Study and Prognostic Assessment by Diffusion-Weighted MRI
Matthew J. Wieduwilt, Francisco Valles, Samar Issa, Caroline M. Behler, James Hwang, Michael McDermott, Patrick Treseler, Joan O'Brien, Marc A. Shuman, Soonmee Cha, Lloyd E. Damon and James L. Rubenstein
Clin Cancer Res February 15 2012 (18) (4) 1146-1155; DOI: 10.1158/1078-0432.CCR-11-0625
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Clinical Cancer Research
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