Diffusion-Weighted MR Imaging in Lymphoma

1. Diffusion-Weighted MR Imaging in Lymphoma Sagun D. Goyal Hematology/Oncology Grand Rounds October 8, 2010

2. Disclosure Speaker has nothing to disclose

3. Outline DW-MRI and rationale for use DW-MRI in oncology DW-MRI in lymphoma Proposed study Should I include XRT side effectsShould I include XRT side effects

4. Background PET/CT is the standard imaging modality used for staging and follow-up in patients with aggressive B-cell lymphomas The literature surrounding the use of DW-MRI for the detection and prediction of response of tumors to therapy has increased over the past few years

5. Rationale for exploring DW-MRI use MRI is readily available Lower cost Minimal risk Non-invasive No contrast required Does not require the use of ionizing radiation May allow for functional assessments similar to SUV in PET scanning Find out cost of MRI vs PET scanFind out cost of MRI vs PET scan

6. Radiation Risk

7. Diffusion-Weighted Imaging Measures random motion of water in tissue Motion decreases in cellular tissue (tumor) Motion increases in necrosis or apoptosis (treated tumor) Can do subjective and quantitative analysis Quantitative measurement is ADC (apparent diffusion coefficient) Does not require contrast

8. Diffusion Weighted MRI: Basic Image Viable tumors High cell density Less water motion Bright (higher signal) Necrotic tumors Few membranes More water motion Dark

9. Apparent Diffusion Coefficient Studies of DW-MRI in various solid tumors indicate Tumor tissue has a lower ADC, and thus, higher signal intensity, than tissue of origin, indicating a greater cellularity, serving as a basis for tumor identification Tumors with high ADCs are more resistant to therapy, likely reflecting tumor hypoxia and necrosis An increase in ADC early during treatment indicates response to therapy

10. Apparent Diffusion Coefficient

11. DWI in predicting tumor response

12. DWI-MRI in Oncology Tumor detection and staging Used in the detection of hepatic metastases Monitoring treatment response Responding patients show a significant rise in ADC values after therapy Tumors studied: HCC, cerebral gliomas, soft-tissue sarcomas, colorectal hepatic metastases Predicting treatment response Cellular tumors that show low baseline pre-treatment ADC values respond better to chemotherapy or XRT than tumors with high pre-treatment ADC values Tumors studied: breast cancer, cerebral gliomas, colorectal hepatic metastases

13. DW-MRI in Lymphoma

15. Objective Design a whole-body MR protocol using exclusively diffusion-weighted imaging (DWI) with respiratory gating and to assess its value for lesion detection and staging in patients with DLBCL with FDG/PET as the reference standard

16. Results 15 patients with DLBCL underwent both PET/CT and whole-body DW-MRI for pre-treatment staging 20 lymph node regions were analyzed per patient Ultimately 296 lymph node regions in 15 patients were analyzed Agreement was 100% for organ involvement (n = 20) Ann Arbor stages agreed in 14 of 15 (93%) patients In one patient, perigastric nodes masked by intense FDG uptake of gastric tumor and also DW-MRI also showed additional cervical LN in this patient

17. Apparent Diffusion CoefficientPatient with concomitant DLBCL and follicular lymphoma

18. Results Based on IWG size criteria DWI matched PET/CT in 277 regions (94%) Sensitivity 90%; Specificity 94% Combining ADC analysis with size measurement Sensitivity 81%; Specificity 100%

19. Conclusion WB-DWI with ADC analysis can be used for lesion detection and staging in patients with DLBCL

21. Objectives Describe DW-MRI features of OALs Determine diagnostic accuracy of ADC for discriminating OALs from other orbital mass lesions Assess whether variations in ADC constitute a reliable biomarker of OAL response to therapy

22. Study design 114 patients with orbital mass lesions were enrolled 38 patients with pathologically-proven OAL underwent serial DW-MRI examination of the orbits ADCs of OALs were compared with those of normal orbital structures and other orbital mass lesions Interval change in ADC of OALs before and after treatment was analyzed in 29 patients

23. Images

24. Results Baseline ADCs in OALs were lower than those in normal structures and other orbital diseases

25. Results Pre- and post-treatment ADCs assessed in 29 patients 10/29 patients had volumetric reduction Accompanied by increase in ADC, n = 7 Preceded by increase in ADC, n = 3 (3 month average) Disease progression in 7 patients Further reduction seen in ADC (preceded progression in 1)

26. Conclusions ADC measure predicts accurate diagnosis of OALs Interval change in ADC after therapy may help predict therapeutic response Change in ADC may precede volumetric change May avoid premature designation of “treatment failure”

27. Questions Is ADC affected by aggressiveness of lymphoma subtype Majority of patients in this study had MALT PET typically not used for low-grade lymphomas

29. Rationale Background Increased tumor cellular density within diagnostic specimens of PCNSL may have prognostic implications Hypothesis Because cellular density may influence measurements of ADC, ADC measured within contrast-enhancing regions might correlate with clinical outcome in patients with PCNSL

30. Methods 18 immunocompetent patients with PCNSL treated with MTX-based chemotherapy followed Pre-treatment DWI-MRI obtained ADC from all enhancing regions measured Mean, 25th percentile ADC, minimum ADC values reported ADC measurements compared to tumor cellularity Survival analysis performed

31. Results Clarify how diff adc values obtained if only single lesionClarify how diff adc values obtained if only single lesion

32. Results ADC25% measurements less than the median value of 692 (low ADC group) were associated with significantly shorter PFS and OS No significant differences in major clinical prognostic factors between low and high ADC groups Age, performance status, tumor volume

33. Results Patients with improved clinical outcome were noted to exhibit a significant decrease in ADC measurements following high-dose MTX chemotherapy

34. Conclusions Whole-body DW-MRI with ADC analysis can be used for staging lymphoma patients Change in ADC measurements after treatment can predict response Pre-therapeutic ADC measurements may also correlate with treatment response and clinical outcome

35. Protocol Diffusion-Weighted MRI in Diffuse Large B-Cell Lymphoma Investigators PI Dr. Marilyn J. Siegel, M.D. Co-investigators Dr. Nina Wagner-Johnston, M.D. Dr. Sagun Goyal, M.D. Dr. Barry A. Siegel, M.D.

36. DLBCL 25-30% of all non-Hodgkin’s lymphomas diagnosed in the U.S. Ongoing protocols seek to minimize treatment in patients with early-stage, low-risk disease and maximize treatment in those patients likely to be refractory to standard therapy Standard approach for evaluating response to 1st-line chemotherapy is PET/CT PET has ability to assess viable tumor in residual masses FDG-PET performed early during course of treatment predicts response and outcome Potential for adaptive treatment strategies

37. DW-MRI Hypothesis DW-MRI will offer a simple and sensitive method for detecting DLBCL lesions and identifying responders early during therapy Implications May allow for adaptive treatment strategies with Decreased radiation burden

38. Primary Aims Estimate the sensitivity of the qualitative assessment of baseline DW-MRI for staging of DLBCL, with FDG-PET/CT as the reference standard Assess the association between change in ADCmax values after 2 cycles of chemotherapy and metabolic response on FDG-PET/CT simultaneously

39. Secondary Aims Estimate the sensitivity of the qualitative assessment of baseline DW-MRI on a lesion basis for detection of DLBCL, with FDG-PET/CT as the reference standard. Assess the correlation between baseline ADC on DW-MRI and baseline SUV on FDG-PET/CT. Assess the association between baseline ADC values and metabolic response on FDG-PET after two cycles of R-CHOP or R-CHOP-like chemotherapy . Assess the association between baseline ADC and complete response by IWG criteria after completion of R-CHOP or R-CHOP-like therapy. Assess the association between change in ADC after completion of two cycles of R-CHOP or R-CHOP-like chemotherapy and complete response by the IWG criteria.

40. Study Overview Prospective, single institution, non-randomized comparison pilot study 50 patients

41. Study Overview Inclusion criteria Patients with newly diagnosed, histologically documented de novo DLBCL Will undergo R-CHOP chemotherapy or therapy with a CHOP-like regimen containing rituximab for curative intent 18 years of age or older All racial and ethnic groups and both males and females Will undergo both baseline DW-MRI and PET-CT studies within 14 days of each other and < 30 days prior to the start of chemotherapy. Will undergo DW-MRI and PET-CT within 17 to 24 days post cycle 2 therapy. Exclusion criteria Prior cytotoxic therapy or rituximab Implanted or accidental exposure to metal fragments, pacemaker, defibrillator, neurostimulator, artificial heart valve, cerebral aneurysm clips. Pregnancy Inability to give informed consent Children, prisoners, institutionalized individuals, mentally disabled patients Diagnosis or treatment for another malignancy within three years of enrollment, with exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

42. Expected outcomes DW-MRI will offer a simple, safe, and sensitive method for detecting DLBCL lesions DW-MRI with ADC mapping will help identify responders early in the course of therapy This trial will be a first step towards establishing standardized criteria for DW-MRI in extra-cranial tumor imaging

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