Whole Body MRI. Dr. Nina Tunariu. Prostate Cancer recurrence, progression and restaging

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1 Whole Body MRI Prostate Cancer recurrence, progression and restaging Dr. Nina Tunariu Consultant Radiology Drug Development Unit and Prostate Targeted Therapies Group Janeiro 2018

2 Evolving Treatment Paradigms & Disease patterns (visceral disease & local complications) CT & BS vs? 2 nd generation imaging PCa molecular / genetic heterogeneity BRCA, ARv7 2 nd generation sequencing Patients & clinicians expectations Technology advances Fusion MRI-US Robots & MRI-Linac CTC & Apheresis

3 Why (WBDW) MRI High sensitivity for bone marrow involvement Large volume Body Coverage with high-contrast resolution Spine (Bone MSCC) & Pelvis (local disease) & Abdomen (liver & ureteric metastases) No intravenous contrast agent tracer administration No radiation exposure Can be performed on standard MRI scanner min for study and min of overall visit time Why now? Surface-coil technologies and parallel imaging acquisition and diffusionweighted imaging with background suppression (DWIBS) Improves sensitivity and specificity Anatomical functional (tumour cellularity) techniques without the need of registration Early response in bone marrow disease to therapy without the flare phenomenon 3

4 Diffusion Weighted Imaging DWI water movement in tissues is neither entirely free nor random, due to its interaction with cell membranes, intracellular organelles, macromolecules and flows with blood vessels and ducts DW-MRI consists of modified standard T2w sequence, incorporating diffusion sensitizing gradients. The strength and duration of the application of diffusion gradients is indicated by their b value ADC apparent diffusion coefficient (mm 2 /s): quantitative measure of net (impeded) water diffusivity of tissues (at least 2 b values) water ADC= slope of the line Water Low cellularity High cellularity Koh DM.et al Eur Radiol Nov;19(11): ADC r% = 10-20

5 Diffusion Weighted Imaging DWI B value 1 (50 s/mm water movement 2 ) in tissues B value is 2 (900 s/mm neither 2 ) entirely free ADC nor random, due to its interaction T1w T2w with cell membranes, intracellular organelles, macromolecules and flows with blood vessels and ducts DW-MRI consists of modified standard T2w sequence, incorporating diffusion sensitizing gradients. The strength and duration of the application of diffusion gradients is indicated by their b value ADC apparent diffusion coefficient (mm 2 /s): quantitative measure of net (impeded) water diffusivity of tissues Treated Bone Metastasis vs Active Tumour water ADC= slope of the line Urine Low cellularity High cellularity 3000 x10-6 mm 2 /s 1500 x10-6 mm 2 /s 600 x10-6 mm 2 /s

6 Whole Body MRI with DWI Low Intermediate High b value ADC 3 b values STIR slices 4-6 stations 5mm slice thickness min DWI min T1/T2 2 planes anatomical

7 Whole Body MRI with DWI One Stop Shop MRI pelvis Local disease assessment CT & bone scan (staging nodal, visceral) MRI spine (?Malignant Spinal Cord Compression - MSCC, fractures, bone metastases response)!weakness subcentimetre lung metastases % in Pca subcentimetre nodes 18F-Choline-PET

8 Local recurrence detection mpmri and PET CT similar performance & complementary

9 Nodal Staging & Recurrence Availability vs Expertise vs Evidence atypical locations & round morphology & positive DWI & >5-6mm CT DWI ADC DWI T2w Choline - PET ADC Non-specific uptake DWI T2w Choline - PET Biopsy proven retropectoral node in M0 patient PSA 134

10 Nodal Staging & Recurrence Technique and Results heterogeneity Functional and Targeted Lymph Node Imaging in Prostate Cancer: Current Status and Future Challenges Harriet C. Thoeny, Sebastiano Barbieri, Johannes M. Froehlich, Baris Turkbey Peter L. Choyke Radiology Dec;285(3):

11 Nodal Staging MRI plus DWI and no USPIO Sensitivity for subcentimetre nodes is 40-50%

12 Nodal Recurrence 54-year-old man with nodal recurrence prostate cancer after radical prostatectomy, salvage external-beam radiotherapy and salvage lymph node dissection PSMA PET/CT USPIO (ultrasmall superparamagnetic particles of iron oxide) -MRI 3 nodes on PSMA & 15 nodes on USPIO 44 positive nodes at surgery PSA 2.2 ng/ml post surgery so ADT was initiated

13 Nodal Metastases Detection on PET Imaging improved considerably by new tracers but remains suboptimal The future? Rephrase the questions? Design imaging trials that answer clinical questions? What is the gold standard? Which lymphadenectomy protocol Is there a role of stratification based on 2 nd generation imaging vs EPLND? Do we need a biopsy for the imaging classified M0/M1 small nodes? Can we biopsy 2-8mm nodes? What is the incidence of true positive <6mm M0/M1 nodes? Does it impact patient OS, PFS & MFS if we treat all PET / MRI positive nodes? Is disease free survival dependent on the number of Imaging Positive nodes?

14 Bone Metastases Detection Low volume disease? M0? Bone scan 18F-choline-PET NaF-PET BS + SPECT NaF-PET WBMR_DWI 18 F-fluorocholine and 18 F-fluoride PET/CT scans indicated multiple bone metastases metastatic disease in 20% of patients with high-risk prostate cancer without conclusive evidence of metastases on a previous 99m Tc-MDP bone scan Kjölhede H, et al. BJU Int Ivan Jambor, et al. SKELETA clinical trial. Acta Oncologica, 2015

15 Bone Metastases Detection 26 breast & 27 prostate cancer patients high risk of bone metastases underwent 99mTc-HDP BS, 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT and wbmri-dwi 5 independent reviewers for each individual modality without the knowledge of other imaging findings. final metastatic status based on the consensus reading, clinical and imaging follow-up (6 32 months) findings of each imaging modality were compared with best valuable comparator (BVC) in order to define their nature Ivan Jambor, et al. SKELETA clinical trial. Acta Oncologica, 2015

16 Gold Standard Best Valuable Comparator Bone Metastases Detection Whole body MRI, including DWI, was as accurate as 18F-NaF PET/CT for the detection of bone metastases in high risk BCa and PCa patients. In the context of nuclear medicine techniques, 99mTc-HDP SPECT/CT was superior to 99mTc-HDP BS, and SPECT, especially SPECT/CT having less equivocal findings. Ivan Jambor, et al. SKELETA clinical trial. Acta Oncologica, 2015

17 Bone Metastases Detection 10 studies including patients MRI shows excellent sensitivity and specificity for the detection of bone metastasis in prostate cancer. Studies using two or more planes for assessment showed the highest sensitivity and specificity, while diagnostic performance was consistently high across multiple subgroups.

18 Is the cancer in my bones? Osteoporotic fracture with suspicious one focus above Negative for metastases even after targeted review PSA 7.1 ng/ml PSA 34 ng/ml PSA 109 ng/ml 3 months DW-MRI February 2011 August 2011 DW-MRI October 2011 DW-MRI December 2011

19 Is the cancer in my bones? WB-DWI inverted b900 PSA 154 ng/ml Small-volume bone metastases PSA 34 ng/ml PSA 109 ng/ml WB-DWI, whole-body diffusion-weighted imaging; PSA, prostate-specific antigen.

20 FLARE or Progression? Confirmatory Bone Scan APRIL 2015 PSA 16 ng/ml OCT 2015 PSA 4.8 ng/ml JAN 2016 PSA 6.5 ng/ml

21 FLARE or Progression? APRIL 2015 PSA 16 ng/ml OCT 2015 PSA 4.8 ng/ml BE AWARE of PSA / TUMOUR BURDEN DISCORDANCE

22 Malignant Superscan Stable Appearances NOT STABLE DISEASE

23 Malignant Superscan

24 Malignant Superscan ADC 900 Availability vs Expertise vs Evidence ADC 1300 ADC hours & hour & 450

25 Take home Messages 2 nd Generation Imaging is becoming a Game Changer Local staging & local recurrence MRI & PET are complimentary strengths and weakness of each technique Nodal Staging remains suboptimal Future trials will help further stratification Bone Metastases WBMRI advantage of ONE Stop SHOP Detection and Response in Bone Metastases (commonest metastatic site) without FLARE phenomenon confounder Detection of MSCC and fractures Evaluation of Nodal and Visceral Disease