Diffusion-Weighted MR Imaging Derived Apparent Diffusion Coefficient Is Predictive of Clinical Outcome in Primary Central Nervous System Lymphoma

BACKGROUND AND PURPOSE: There is evidence that increased tumor cellular density within diagnostic specimens of primary central nervous system lymphoma (PCNSL) may have significant prognostic implications. Because cellular density may influence measurements of apparent diffusion coefficient (ADC) by using diffusion-weighted MR imaging (DWI), we hypothesized that ADC measured from contrast-enhancing regions might correlate with clinical outcome in patients with PCNSL. MATERIALS AND METHODS: PCNSL tumors from 18 immunocompetent patients, treated uniformly with methotrexate-based chemotherapy, were studied with pretherapeutic DWI. Enhancing lesions were diagnosed by pathologic analysis as high-grade B-cell lymphomas. Regions of interest were placed around all enhancing lesions allowing calculation of mean, 25th percentile (ADC25%), and minimum ADC values. Histopathologic tumor cellularity was quantitatively measured in all patients. High and low ADC groups were stratified by the median ADC value of the cohort. The Welch t test assessed differences between groups. The Pearson correlation examined relationships between ADC measurements and tumor cellular density. Single and multivariable survival analysis was performed. RESULTS: We detected significant intra- and intertumor heterogeneity in ADC measurements. An inverse correlation between cellular density and ADC measurements was observed (P < .05). ADC25% measurements less than the median value of 692 (low ADC group) were associated with significantly shorter progression-free and overall survival. Patients with improved clinical outcome were noted to exhibit a significant decrease in ADC measurements following high-dose methotrexate chemotherapy. CONCLUSIONS: Our study provides evidence that ADC measurements within contrast-enhancing regions of PCNSL tumors may provide noninvasive insight into clinical outcome.

[1]  P. Grant,et al.  Diffusion MR imaging. Theory and applications. , 1999, Neuroimaging clinics of North America.

[2]  C. Meyer,et al.  Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[3]  J. Cox,et al.  Primary malignant lymphoma of the central nervous system. Results of treatment of 11 cases and review of the literature. , 1986, Journal of neurosurgery.

[4]  L. Deangelis,et al.  Long-term survival in primary CNS lymphoma. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  D. Mikulis,et al.  Diffusion-weighted imaging and single-voxel MR spectroscopy in a case of malignant cerebral lymphoma , 2003, Neuroradiology.

[6]  L. Deangelis,et al.  Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  R. Turner,et al.  Diffusion MR imaging: clinical applications. , 1992, AJR. American journal of roentgenology.

[8]  Stephan E Maier,et al.  Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  S L Meeks,et al.  Initial clinical experience with frameless stereotactic radiosurgery: analysis of accuracy and feasibility. , 2001, International journal of radiation oncology, biology, physics.

[10]  P. Kleihues,et al.  The Use of the Monoclonal Antibody Ki-67 in the Identification of Proliferating Cells: Application to Surgical Neuropathology , 1986, The American journal of surgical pathology.

[11]  T. Batchelor,et al.  Differential gene expression in central nervous system lymphoma. , 2009, Blood.

[12]  Jon D Wilson,et al.  Primary central nervous system lymphoma. , 2008, Archives of pathology & laboratory medicine.

[13]  J. Gore,et al.  The impact of a bladder cancer diagnosis on smoking behavior: An opportunity to improve care. , 2010 .

[14]  C. Calli,et al.  Minimum apparent diffusion coefficients in the evaluation of brain tumors. , 2005, European journal of radiology.

[15]  J. M. Taylor,et al.  Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. , 2000, Journal of the National Cancer Institute.

[16]  Descriptive epidemiology of primary brain and CNS tumors: results from the Central Brain Tumor Registry of the United States, 1990-1994. , 1999, Neuro-oncology.

[17]  J. Armitage,et al.  Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  K. Hoang-Xuan,et al.  Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  W. Reiche,et al.  Diffusion-weighted MR imaging improves diagnosis of CNS lymphomas A report of four cases with common and uncommon imaging features , 2007, Clinical Neurology and Neurosurgery.

[20]  J. Blay,et al.  High-dose methotrexate for the treatment of primary cerebral lymphomas: analysis of survival and late neurologic toxicity in a retrospective series. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  J. Fridlyand,et al.  Gene expression and angiotropism in primary CNS lymphoma. , 2006, Blood.

[22]  D. Kraemer,et al.  Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. , 2000, Neurosurgery.

[23]  M. Taniwaki,et al.  Effectiveness and Limitation of Gamma Knife Radiosurgery for Relapsed Central Nervous System Lymphoma: A Retrospective Analysis in One Institution , 2007, International journal of hematology.

[24]  Janet E Olson,et al.  The continuing increase in the incidence of primary central nervous system non‐Hodgkin lymphoma , 2002, Cancer.

[25]  Howard Schulman,et al.  Protein biomarker identification in the CSF of patients with CNS lymphoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  P. Kelly,et al.  Computer‐assisted stereotaxic biopsy for the diagnosis of primary central nervous system lymphoma , 1987, Neurology.

[27]  P. Grenier,et al.  MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. , 1986, Radiology.

[28]  J. Fridlyand,et al.  Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  S. Ng,et al.  Primary Cerebral Lymphoma and Glioblastoma Multiforme: Differences in Diffusion Characteristics Evaluated with Diffusion Tensor Imaging , 2008, American Journal of Neuroradiology.

[30]  Bradford A Moffat,et al.  Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  James M Provenzale,et al.  Lymphomas and high-grade astrocytomas: comparison of water diffusibility and histologic characteristics. , 2002, Radiology.

[32]  F. Hochberg,et al.  Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: long-term outcome. , 1994, Journal of neurosurgery.

[33]  V. Jellús,et al.  Diffusion-weighted MR imaging of intracerebral masses: comparison with conventional MR imaging and histologic findings. , 2001, AJNR. American journal of neuroradiology.