1. MR-guided focal laser therapy
Jurgen Fütterer MD PhD
Department of Radiology
Radboud University Medical Center
Nijmegen, The Netherlands

2. Image guided ablations provide a minimally invasive approach to prostate cancer therapy and is gaining clinical acceptance
Focal therapy is an emerging treatment modality for localized prostate cancer that aims to reduce the morbidity seen with radical therapy  maintaining cancer control

3. Current treatment - low and intermediate grade: Active surveillance
Background
Current treatment - low and intermediate grade:
Active surveillance
Radical therapy (radiotherapy - prostatectomy)
 High chance on morbidity and decreased quality of life
- urinary incontinence (5–20%)
- erectile dysfunction (30–70%)
- bowel toxicity (5–10%)
240,000 newly diagnosed patients and 30,000 deaths in the United States in 2013

4. image guided interventions 
Minimally invasive, preserving body integrity, less side-effects
Real economic impact:
- short recovery
- ambulatory patient care
- maintaining the patient in his social environment
Based on technical innovations :
- high investment of companies in this field
Allows combination of strategies :
- identification of specific targets (molecular imaging)
- development of focal therapies
- combined with new targeted therapies
11 November 2015

5. Laser ablation
Laser-induced interstitial thermal therapy (LITT)  laser ablation (LA)  technique which was originally developed to treat brain tumors
A laser fiber is positioned into the lesion under image guidance
The laser fiber is placed inside a cooling catheter throughout the ablation, to prevent carbonization of the adjacent tissue and to improve laser light penetration depth

6. ADVANTAGES of using MRI
excellent functional soft-tissue contrast (3D)
able to localize the tumor
to target it with probes
to ‘real-time’ monitor and control the image guided intervention  temperature maps
no X-rays to acquire images
11 November 2015

7. MR-guided focal laser ablation
+ Fast: 2 – 4 minutes per ablation 1.5 hour treatment + Accurate Sharp transition zone between necrotic and viable tissue + Minimal invasive: Local anesthesia in outpatient setting + MR compatible: Tumor localization, targeting, treatment monitoring and temperature mapping

8. Precision and Control Volumetric heating + Rapid energy deposition 
Sharp transition zone between dead and viable tissue
Transition zone in RF and Cryo can be 5-10 mm
980nm Laser transition zone is less than 1 mm

9. REAL-TIME TEMPERATURE MAPPING

11. Validation of focal MRgLA in an ablate - resect study
The MRI-calculated ablated volume correlated well with histopathology.
MRgLA creates confluent ablation with no evidence of viable cells in treated regions
Linder, et al. European Urology Volume 57, Issue 6, June 2010, Pages

12. Calculation ablation volume Damage estimation map:
Materials and Methods
Calculation ablation volume
Damage estimation map:
Length and width measured
Size of ablation volume was calculated with ellipsoid formula
Calculation ablation volume
T1-weighted contrasted enhanced images:
Contouring non enhancing zone by 2 radiologists in consensus
Area per slice calculated and summed
Calculation ablation volume
Radical prostatectomy specimen
Contouring necrotic, transition zone and viable tissue by experienced urogenital pathologist
Area per slice calculated and summed
Axial T1-w CE
H&E staining
Damage estimation map

13. MR-guided FLA was performed in 5 patients
Results
MR-guided FLA was performed in 5 patients
No intra-operative complications
All patients discharged after 1 hour
Radical prostatectomies uncomplicated
Table 1: Patient characteristics
Patient
N = 5
Age (y)
PSA (ng/mL)
5.7 – 16.2
Gleason Score 2x 1x
GS 3 + 2
GS 3 + 3
GS 3 + 4

14. Results Software overestimates final necrotic volume
T1-w ce MR images give better indication of necrotic volume
Clear volume correlation between T1-w CE images and pathology
Laser software vs
pathology
T1-w CE images
Median ratio
6.73
0.93
8.77
Range
1.60 – 29.20
0.46 – 2.40
2.11 – 21.47
Pearson correlation coefficient
0.33
0.94
0.26 R2
0.11
0.88
0.07

15. Homogeneous necrotic ablation zone
Results
Histopathology:
Homogeneous necrotic ablation zone
Transition zone necrotic and viable tissue was 0 – 5 mm
Reactive changes in transition zone
Higher mitotic index
Neovascularization
Het is in ieder geval van andere tumoren algemeen bekend dat ter plaatse van het invasiefront veel moleculaire events plaats vinden: toename vascularisatie, afbraak stroma, ontsteking, verhoogd metabolisme tumorcellen, en dus ook verhoogde delingsactiviteit  Aan rand ablatiezone geven we tumorweefsel een boost
H&E staining
H&E staining

16. MR-guided focal laser ablation of prostate cancer: 1-year follow-up
Jurgen Futterer

17. Purpose
To evaluate therapy success, complications, technical feasibility and safety of MR-guided focal laser ablation as primary treatment for prostate cancer

18. Materials and Methods Inclusion criteria:
Prostate specific antigen (PSA) level ≤20 & Gleason Score ≤7
No previous prostate treatment
No evidence for nodal or metastatic disease
MRI visible lesion
Exclusion criteria:
Patients with contra-indications to MRI or transrectal FLA

19. Materials and Methods Transrectal MR-guided focal laser ablation:
Local anesthesia
3T MR scanner

20. Materials and Methods Transrectal MR-guided focal laser ablation:
Needle guide inserted in the rectum
Dynatrim (Invivo, Philips) to direct the needle guide
Laser fiber inserted (Medtronic)

21. Materials and Methods
Continuously monitoring with real-time PRF-MR thermometry
(TMAP: TR 44.8 ms, TE ms, flip angle 30°,
spatial resolution 1.5x1.5 mm, slice thickness
5 mm, temporal resolution of 4.4s)
Single plane through laser fibre

22. Materials and Methods Multiple ablations; depending on size of lesion
T1-weighted fat-saturated contrast enhanced images acquired directly after ablation
(T1 TSE axial: TR 704 ms, TE 13 ms,
flip angle 120°, resolution 0.8 x0.8 mm,
slice thickness 3 mm)

23. Materials and Methods Follow-up:
IPSS, SHIM to monitor post-treatment morbidity:
Incontinence (IPSS)
diagnosis of erectile dysfunction (SHIM)

24. Results
41 patients successfully treated with MR-guided focal laser ablation
All procedures were technical feasible
All patients dismissed at the same day of treatment
No intra-procedural complications

25. Results Median follow-up was 12 months (range, 10 – 16 months)
One patient was lost in follow-up
PSA level decreased in all patients (median 7.9  3.9 ng/mL)
No significant change in IPSS and SHIM scores

26. Results
Multi-parametric MRI showed presence of residual or recurrent tumor in 5 out of 40 patients (13%)
Four out of 5 were successfully retreated

27. Results - Case 64 year old man, PSA 8.5 Left peripheral zone: GS 3+3=6
Axial T2w
Axial DCE
Axial ADC

28. Results - Case 64 y, PSA 8.5, GS 3+3=6
MR-guided focal laser ablation, multiple ablations 2min 12W
Contrast-enhanced images, directly after ablation
TMAP
T1WCE

29. Results – Case 64 y, PSA 8.5, GS 3+3=6 3 weeks post treatment: PSA 1.3
Axial T2w
Axial DCE
Axial ADC

30. Results – Case 64 y, PSA 8.5, GS 3+3=6
6 months post treatment: PSA 3.7
Axial T2w
Axial DCE
Axial ADC

31. Results – Case 64 y, PSA 8.5, GS 3+3=6
12 months post treatment: PSA 3.3
MR-guided biopsy: No malignancy
Axial T2w
Axial DCE
Axial ADC

32. Discussion / Conclusion
Transrectal MR-guided focal laser ablation of newly diagnosed PCa was technically feasible and safe
PSA level decreased in all patients
Follow-up MRI showed no residual or recurrent cancer in 87%; indicating local cancer control without compromising for increased morbidity or decreased quality of life

33. Conclusion:
Prostate cancer is a multifocal disease in the majority of cases
MRI targeted focal therapy of the prostate is possible with the present techniques, however the one method is more feasible than the other
These ‘novel’ procedures require validation in prospective clinical trials with more patients and longer follow-up and must be compared to active surveillance and radical therapies in ‘randomized’ controlled trials