Optimal Imaging and Technical Aspects of Prostate SRT

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Philippa Garrett
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1 Optimal Imaging and Technical Aspects of Prostate SRT Maris Mezeckis Dr., MBA, Vladislav Buryk Dr., PhD Sigulda Hospital Stereotactic Radiosurgery centre

$25 Gy (range 35 40 Gy) over 5 fractions (given daily among >95% of patients, every other day for the remainder) For the homogenous planning, dose was normalized to the 90% isodose line in order for$

2 Homogeneous planning: PTV=prostate + 5 mm, 3 mm posterior direction Heterogeneous planning (i.e., HDR-like dosimetry) PTV=prostate + 2 mm, 0 mm posteriorly The course of radiotherapy consisted of a median of Gy (range Gy) over 5 fractions (given daily among >95% of patients, every other day for the remainder) For the homogenous planning, dose was normalized to the 90% isodose line in order for the prescription dose to cover at least 95% of the PTV NOTE! HDR-like dosimetry has normalisation rate of 70% and lower

5 EUA Guidelines

planes Robotic radiosurgery not linked to certain number of axes and

6 LINAC v. robotic radiosurgery LINAC radiosurgery rotation in single (or in few) planes Robotic radiosurgery not linked to certain number of axes and planes (non-isocentric, non-coplanar) Cone-beam CT finds the right position only before treatment Robotic radiosurgery provides continuous tracking

$Inter-fractional deformations (bladder volume, position of intestines etc.$ $hard to evaluate) Daily USS (hand USS) Intra-fractional motion - automatic$ $inter-fractional deformations and alignment kv images monitoring of$

7 CyberKnife system Image guided, but but 2D images marker dependent Inter-fractional deformations (bladder volume, position of intestines etc. hard to evaluate) Daily USS (hand USS) Intra-fractional motion - automatic adjustment of the beam LINAC-based systems CBCT, kv images CBCT inter-fractional deformations and alignment kv images monitoring of intrafractional motion If intrafractional motion above defined value holds-up dose delivery repositioning continue dose delivery

8 Different dose distribution: Homogeneous dose distribution ( 80% normalization rate) 5mm (4mm) margins, except 3mm (2mm) posteriorly HDR-like (maximum dose not limited inside the target, up to % prescribed dose). 2mm margins except 0mm posteriorly Moderately heterogenous planning with focal increase of the dose Fuller D. et al. (SanDiego, CA) ASCO GU Symposium, Orlando FL, 6/02/2017

Pretreatment evaluation&consultation PSA dynamics, biopsy data, mpmri Low risk, intermediate favorable risk Intermediate unfavorable, high-risk patient (if patient refuses other treatment methods, if

9 Pretreatment evaluation&consultation PSA dynamics, biopsy data, mpmri Low risk, intermediate favorable risk Intermediate unfavorable, high-risk patient (if patient refuses other treatment methods, if data are included in clinical trial or multiinstitutional consortium) Patient anatomy Prostate volume, relation to bladder and rectum etc. Visibility of dominant lesion in mpmri (intermediate/high risk patients)

Fiducial marker placement 4 (3) markers should be placed in

Biplane probe (coron&sag) Probe holder/stabilizer Template grid

to localize markers in 3D space) Markers should be placed by

10 Fiducial marker placement 4 (3) markers should be placed in coronal plane at least 20mm from each other Trans-perineal Biplane probe (coron&sag) Probe holder/stabilizer Template grid Transrectal placement Biplane probe End-fire probe (problematic to localize markers in 3D space) Markers should be placed by radiation oncologist or urologist* *good collaboration is mandatory for QA

11 1.2x3mm cylindric v. 0.6x10mm thread-like (GA)

12 Other aspects of fine needle implantation

13 Marker comparison Conventional (cylindric) (CIVCO, IzziMedical etc.) Paired (IziMedical, CIVCO etc.) Thread like (Gold Anchor) Parameters 18G 3-5mmx1mm Single or paired 18G 2 paired 3x0.9mm with 20mm distance Benefits Cheap 2 markers are implanted in one penetration of rectal wall 20mm spacing guaranteed Disadvantages 5-7 days lead time More artifacts on CT Poor visibility on 1.5T MRI T2 (if 99.9 (pure) gold) Higher price Longer learning curve for perfect implantation (?) 22G GA200-10B (transrectal) 25G GA (transperineal) Imaging on same day Less artifacts on CT Good visibility on T2 (especially 3T) Less pain-full, less complications Higher price Longer learning curve for perfect implantation

bladder, outer rectal wall above perineum, testes 2. T1 3. T2 4. T1 w contrast 5. ADC map images 6.

14 Main options for imaging 1. CT- reference image, for calculation. Also suitable for contouring of some anatomical structures - seminal vesicles, base of the prostate, bladder, outer rectal wall above perineum, testes 2. T1 3. T2 4. T1 w contrast 5. ADC map images 6. DWI images 7. PET-CT for visualization of dominant lesion 8. CT for urethra visualization 9. Precise NVB visualization (pelvic MR or CT angiography)

PIRADS v2: lesion (GTV) delineation PIRADS 1 Very low (clinically significant cancer is highly unlikely to be present) PIRADS 2 Low (clinically significant cancer is unlikely to be present) PIRADS 3

15 PIRADS v2: lesion (GTV) delineation PIRADS 1 Very low (clinically significant cancer is highly unlikely to be present) PIRADS 2 Low (clinically significant cancer is unlikely to be present) PIRADS 3 Intermediate (the presence of clinically significant cancer is equivocal) PIRADS 4 High (clinically significant cancer is likely to be present) PIRADS 5 Very high (clinically significant cancer is highly likely to be present)

Contouring T2W images are used to discern prostatic zonal

evaluate for seminal vesicle invasion, EPE, and nodal

delineation as well as perineal segment delineation of

16 Contouring T2W images are used to discern prostatic zonal anatomy, assess abnormalities within the gland, and to evaluate for seminal vesicle invasion, EPE, and nodal involvement (PIRADS v2) Best for prostate anatomy delineation as well as perineal segment delineation of rectal wall, urethra delineation (if catheter is absent), penile bulb and NVB delineation

Lesions on T2 according PIRADS v2 On T2W images, clinically significant cancers in the PZ usually appear as round or ill defined hypointense focal lesions.

17 Lesions on T2 according PIRADS v2 On T2W images, clinically significant cancers in the PZ usually appear as round or ill defined hypointense focal lesions. However, this appearance is not specific and can be seen in various conditions such as prostatitis, hemorrhage, glandular atrophy, benign hyperplasia, biopsy related scars, and after therapy (hormone, ablation, etc.). The T2W features of TZ tumors include non circumscribed homogeneous, moderately hypointense lesions ( erased charcoal or smudgy fingerprint appearance), spiculated margins, lenticular shape, absence of a complete hypointense capsule, and invasion of the urethral sphincter and anterior fibromuscular stroma. The more features present, the higher the likelihood of a clinically significant TZ cancer.

18 T1-weighted T1W images are used primarily to determine the presence of hemorrhage within the prostate and seminal vesicles and to delineate the outline of the gland (PIRADS v2). For contouring seminal vesicles, NVB.

Most clinically significant cancers have restricted/impeded diffusion compared to normal tissues and thus appear hypointense on grey scale ADC maps.

19 ADC map according to PIRADS v2 The ADC map is a display of ADC values for each voxel in an image. In most current clinical implementations, it uses two or more b values and a monoexponential model of signal decay with increasing b values to calculate ADC values. Most clinically significant cancers have restricted/impeded diffusion compared to normal tissues and thus appear hypointense on grey scale ADC maps. High b value images utilize a b value 1400 sec/mm2. They display preservation of signal in areas of restricted/impeded diffusion compared with normal tissues, which demonstrate diminished signal due to greater diffusion between applications of gradients with different b values.

20 Dynamic Contrast Enhanced (DCE) MRI (T1 with gadolinium contrast) Hemorrhages are bright in pre-contrast series Early contrast enhancement in PIRADS 4 and PIRADS 5 lesions and faster wash-out

21 PET-CT for high-risk pca Precise co-registration of PET and CT might be problematic, therefore T2, ADC/DWI, T1 w. contrast might increase precision of lesion contouring An isocontour of 50%SUVmax in PSMA-PET resulted in visually concordant tumor extension in comparison to mpmri (T2w and DW) For 89.4 % of sections containing a tumor according to mpmri, the tumor was also identified in total or near-total agreement by PSMA-PET Vice versa for 96.8 % of the sections identified as tumor bearing by PSMA-PET the tumor was also found in total or near-total agreement by MP-MRI [Giesel et al., Intra-individual comparison of 68Ga-PSMA-11-PET/CT and multi-parametricmr for imaging of primary prostate cancer, Eur J Nucl Med Mol Imaging (2016) 43: ]

22 [Giesel et al., Intra-individual comparison of 68Ga-PSMA-11-PET/CT and multi-parametricmr for imaging of primary prostate cancer, Eur J Nucl Med Mol Imaging (2016) 43: ]

distribution Urethra marking methods: Catheter Only on the day of imaging All

23 CT topometry: urethra visualization Mandatory for heterogenous dose distribution Beneficial to avoid unnecessary hot spots in urethra in homogenous dose distribution Urethra marking methods: Catheter Only on the day of imaging All through the treatment T2 imaging on MRI topometry CT during miction of contrast filled bladder

24 mpmri topometry MultPlan /Precision allows to import primary image + 5 auxiliary images Low-risk pca no dominant lesion in prostate CT primary 1. T2 2. T

25 Intermediate risk with dominant lesion (PIRADS VI-V) PET-CT absent 1. CT-primary 2. T2 3. T1 4. ADC 5. DWI b CT for urethra visualization

26 High-riska pca with dominant lesion (PIRADS V) PET-CT present 1. CT-primary 2. CT (PET-registered) 3. PET 4. T2 5. T1 6. ADC or DWI b /-Urethra visualization?

27 Conclusions (1) There are significant variation in treatment protocols for prostate cancer radiosurgery Different availability of medical technologies Different approaches Despite variations in treatment protocols published results are good, superior to historical data Evidence is not sufficient to prove superiority of certain approaches Choose approach what allows to reach uncompromised quality, depending on: Available medical technologies Patient work-flow Available staff

28 Conclusions (1) Plan imaging methods before for appropriate imaging depending on: pca risk group Low-risk pca: CTV=prostate, homogenous dose distribution, urethra marking optional Intermediate, high-risk pca: to visualize and mark dominant lesions and urethra. Prescribe heterogenous dose distribution to minimize side effects and maximize potential effect Multi-institutional consortiums might help to compare different approaches General Recommendations on Minimum Requirements and Consensus Guidelines might be helpful for harmonization of treatment protocols

29 Office Cell:

30 1-2 days Work-flow depending on marker type Conventional (cylindric) markers Preparation for marker implantation (1 day) Marker implantation 5-7 days Imaging 7-10 days Thread like (Gold Anchor) or paired markers Preparation for marker implantation&imaging (1 day) Marker implantation, imaging

31 Dose-escalated robotic SBRT for stage I II prostate cancer; Maier et al. Frontiers in Oncology RadiationOncology April 2015 Volume5 Article48 2 Extremely hypofx RT 7Gy x 5fx=35Gy 7.25Gy x 5fx=36.25Gy 8Gy x 5gfx=40Gy 12Gy x 4fx=48Gy EQD2 Gy/fx 86.5 Gy 92.2 Gy 110,6 Gy Gy

32 Heterogenous prescription&planning HDR-like dose distribution Very tight margins (2mm, 0mm post.) Wide high dose zones inside the target Urethra has to be precisely located(catheter)&spared Normalisation up to 66% (maximum up to 150%) Dose 38Gy in 4fx Heterogenous dose distribution Margins 5 and 3mm (4 and 2mm) Prescribed (marginal dose) 35Gy in 5fx, norm.70-80% GTV >40Gy Fuller D. et al. (SanDiego, CA) ASCO GU Symposium, Orlando FL, 6/02/2017

33 Different dose distribution patterns (HDR-like) Fuller D. et al. (SanDiego, CA) ASCO GU Symposium, Orlando FL, 16/02/2017

37 Relapse after RT Extremely hypofx RT 7Gy x 5fx=35Gy 7.25Gy x 5fx=36.25Gy 8Gy x 5gfx=40Gy 12Gy x 4fx=48Gy EQD2 Gy/fx 86.5 Gy 92.2 Gy 110,6 Gy Gy

Prostate MRI. Overview. Introduction 2/20/2015. Prostate cancer is most frequently diagnosed noncutaneous cancer in males (25%)

Prostate MRI. Overview. Introduction 2/20/2015. Prostate cancer is most frequently diagnosed noncutaneous cancer in males (25%) Prostate MRI John Bell, MD Introduction Prostate Cancer Screening Staging Anatomy Prostate MRI overview Functional MRI Multiparametric Approach Indications Example Cases Overview Introduction Prostate