Focal Brachytherapy. Juanita Crook MD FRCPC Professor Radia;on Oncology University of Bri;sh Columbia

Transcription

1 Focal Brachytherapy Juanita Crook MD FRCPC Professor Radia;on Oncology University of Bri;sh Columbia

2 Why focal therapy? Screening frequently diagnoses favourable risk with a low disease burden Appropriate for ac;ve surveillance but s;ll not widely accepted Overall ~6% in 2000, 10% in 2005, 40% in 2013 * Whole gland defini;ve treatment may be excessive and associated with toxicity Improved imaging modali;es to define disease burden Natural history is driven by index lesion (largest lesion; highest grade) *National Reviews Urology 2016

3 Defini;ons: Delphi consensus project: World J Urol 2016 Target defini;on Targeted FT: lesion- based treatment Focal therapy: anatomy- based zonal treatment Focussed therapy: lesion- based dose escala;on Failure defini;on Abla;on failure: lesion not destroyed Targe;ng failure: treatment misapplied spa;ally Selec;on failure: pa;ent inappropriate for FT

4 PSA defini;ons of failure (part of prostate remains untreated) ASTRO: 3 consecu;ve rises back- dated to half way between the nadir and first rise Phoenix: nadir + 2 ng/ml (no back- da;ng) Stuagart: nadir ng/ml Based on analysis of PSA kine;cs for 285 pts treated with focal HIFU Median follow up 4.7 years All < T2, PSA < 15 ng/ml, GS < 7 Median nadir 12.9 weeks 25% clinical failure; 24 pts + biopsy, 47 pts addi;onal treatment Best predictor was PSA nadir (or PSA velocity > 0.3 ng/ml/ year)

5 Choice of modality Proven efficacy in whole gland treatment Capacity to monitor accuracy of treatment delivery Well- established dose response rela;onship Op;ons: LDR or HDR brachytherapy Cryotherapy HIFU PDT, IEP, RFA, laser

6 Planning scenarios Valerio, M. Europ Urol 2014

7 Focal treatment planning PCa is mul;focal in ~ 80% of cases But up to 1/3 are unilateral And, not all tumours require treatment (clinically insignificant) Dominant lesion drives the natural history Target volume may be focal, hemi- gland, dog- leg, etc Most series have aaempted to treat all known disease Required margin is unknown

8 Target volume defini;ons (radiotherapy) F- GTV: clinically demonstrated disease Fusion of T2 hypo intense lesion, with ADC and DCE F- CTV: F- GTV + clinically insignificant disease (if treated) F- PTV: need to add margin to F- GTV for uncertainty in image iden;fica;on, image registra;on and dose delivery Restrict boundaries because of OAR (no margin posteriorly b/o rectum, no overlap with urethra)

9 Margin defini;on Mason et al, Brachytherapy pa;ents treated with focal boost HDR mpmri (1.5 T, T2W, DWI, DCE, no MRSI, no endorectal coil) Rigid registra;on of T2, ADC map and DCE Contoured by 2 radiologists and repeated (4 sets of contours) GTV taken as sum of abnormali;es on T2, ADC and DCE T2 with GTV info registered to intra op TRUS with HDR needles

10 Quan;fica;on of uncertain;es to determine margin Contours: Lep/right: 3.7 mm/3.4 mm Ant/post: 4.9 mm/2.1 mm Sup/inf: 3.8 mm/3.8 mm Image registra;on: L- R: 1.6 mm A- P: 1.6 mm S- I: 2.8 mm F- PTV: single isotropic margin of 4.5 mm

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14 Pa;ent Selec;on (Langley et al BJUI 2012) Interna;onal Consensus Mee;ng on Focal LDR Brachytherapy Life expectancy > 10 years PSA < 15 ng/ml mpmri (T1W/T2W, DWI, DCE +/- MRSI) Template guided mapping biopsy Unilateral disease < 0.5 ml Maximum cancer length 10 mm Clinically insignificant disease on contralateral side < 3 mm Gleason score 6-7 (3+4) Stage < T2B Size < 60 cc

15 LDR FOCAL BRACHYTHERAPY

16 LDR reports: JM Cosset Brachytherapy 2013 n=21, mpmri and # biopsies > 20 Unilateral, T1c/T2a, PSA< 10 ng/ml GS 3+4 or less <25% cores involved and not > 50% in any core 34% of prostate volume (20-48%: 7-22 cc) needles; mean 39 seeds (26-57) Prostate volumes cc (mean 42 cc) Mean D90 F- PTV 183 Gy

17 Pilot study of focal BT Cosset et al BT 2013 high resolu;on MRI and 2 sets of biopsies (min 20 cores) Iodine 125, loose seeds, dynamic dose calcula;on 1 ½ hour procedure Treated volume median 34% of total prostate (20-48%) D90: 183 Gy; V100: 99% 6 months (p=0.04) IIEF recovery faster p=0.014 (median 20 baseline, 3 months, 1 year)

18 Cosset figs 1 and 2 Focal volume cc # seeds Activity: 0.54 U

19 LDR reports: Al Qaisieh IJROBP 2015 n=9, mpmri and template mapping Bx 3 plans for each pt: whole gland, hemi and ultra focal Source ac;vity 0.5 U: stranded F- GTV iden;fied where mpmri agreed with template biopsies F- PTV added 6 mm margin constrained to avoid urethra and remain within 3 mm margin of WG plan

20 Plan comparison Higher dose to target, lower doses to OAR s but very sensitive to source displacement needles seeds CTV D90 UD10 RD2cc 4mm shi? WG % HG % UF %

21 Al- Qaisieh 2015 Seeds not allowed in contralateral gland

22 LDR reports: Laing Radiother and Oncology 2016 n=22, Hemi- gland LDR BT Compared to 120 whole gland controls Target iden;fied with mpmri and TMB Low and intermediate risk PCa, unilateral PSA < 15, T1- T2B, GS < 7 (3+4 or 4+3) Prostate vol < 60 cc (mean 29, range cc) Seed ac;vity 0.5 U Combina;on peripheral strands and Mick loose centrally

23 Laing: hemi gland 2016 Hemi Intra- op Hemi Post- op D90 UD10 UD30 RD2cc 175 Gy 180 Gy 85 G7y 154 Gy 175 Gy 150 Gy 75 Gy Whole 159 Gy 175 Gy 95 Gy NVB ipsilateral 220 Gy, contra lateral 63 Gy

24 Laing et al: hemi gland LDR BT Some seeds may be implanted in contralateral gland

25 T2 FSE HY: 10 mm 3+4 R base Directed biopsy confirmed: CCP 2.8 Randomized to LDR ADC map DCE

26 2 DIL s defined by T2, DCE and ADC Create Boolean addition

27 Boolean addi;on of T2, ADC and DCE DILs and transfer to US

28 Fusion of mpmri to TRUS for transfer of DIL

29 Deformable registra;on

30 Focal salvage 74 Gy in 2007, GS 8, PSA 4.9 Current PSA 3.1, DT 12 mo Bone scan/ct negative MR-guided biopsies Gleason pattern 4

31 LDR focal 11 needles, 33 seeds Prostate volume 15 cc, F-GTV 3.1 cc F-PTV 11 cc

32 Focal LDR Brachytherapy LDR BT well suited to focal treatment of prostate cancer Established radio- biologic basis Known tumoricidal ac;vity in whole gland BT Post implant dosimetry evaluates actual delivered dose: op;mal parameters well- defined Other focal approaches based on ;ssue abla;on less able to predict efficacy and toxicity by quan;ta;ve means

33 HDR FOCAL BRACHYTHERAPY

34 HDR advantages over LDR? Permanent Seed Implants (LDR) Seed loss/migra;on (even with strands!) UF plans very sensi;ve to seed misplacement/ displacement Operator performance Quality evaluated aper the fact: correc;on difficult!

35 HDR Inherent Unique Advantages Dose op;miza;on by manipula;on of dwell ;mes and dwell posi;ons of the stepping source can correct for slight devia;ons in needle placement Cri;cal organ doses (rectum, urethra) can be ;ghtly controlled Poten;al to push extra prosta;c dose where it is needed what you plan is what you get!

36 HDR treatment planning Procedure is US- guided, under anaesthesia Majority of earlier published results from CT- based planning US- based planning growing in popularity Enables needle inser;on, treatment planning and treatment delivery to be performed in one session without moving pa;ent Requires that procedure suite be shielded for treatment delivery, or, conversely, that treatment bunker be equipped for anaesthesia

37 Characteris;cs of US- based HDR Elekta (Nucletron) and Varian each have programs for HDR US- guided and US- planned treatment which allow: July 2014 US image acquisi;on Contouring of anatomy Real- ;me tracking of the needles Inverse treatment planning and plan assessment Plan exporta;on to treatment unit Treatment delivery One step process: < 2 hours start to finish

38 Needle positioning to base Needle insertion under TRUS guidance

39 Iden;fica;on of needle paths

40 Prostate reconstructed with catheters Transfer tubes connected and ready to treat

41 HDR plan: inverse planning algorithm with pre- set constraints to OAR

42 Focal HDR reports Bannerjee 2015 Plans compared for whole gland, hemigland, 1/3 and 1/6 volumes for 5 pa;ents Prostate divided into right and lep halves at urethra; each half divided into base, mid and apical thirds

43 Doses to OAR in % of prescription Bladder 1 cc Rectum 1cc Urethra 0.1 cc Whole gland Hemi gland Third Sixth

44 Focal HDR Reports Mason Brachytherapy 2014 WG, HG and UF plans for 19 Gy single frac;on 6 mm margin for UF plans; 3 mm margin WG Target defined by mpmri and TMB Treatment catheter density increased from 1 cm spacing in WG to 0.75 cm in UF OAR constraints UD10< 22 Gy, UD30 <21 Gy, RD2cc < 15 Gy, RV100=0 F- GTV 0.6 cc ( cc) F- PTV 4.4 cc (( cc)

45 needles UD10 Gray Mason 2014 Udmax Gray RD2cc Gray F- GTV D90 F- PTV D90 whole hemi Ultra focal CT-based planning, caudal shift 4 mm: D90 HG 6%; F-PTV 21% US-based planning, mean uncertainty < 1 mm F-PTV D90 2%

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47 Focal HDR reports Hosni Radiother Oncol 2017 MR- guided focal HDR BT Target defined on mpmri and deformably registered onto post catheter inser;on MRI PTV defined as GTV + 5mm margin except cranio- caudal: 9 mm margin Prescrip;on aim: 16.5 Gy x 2 or 24 Gy x1 7/20 plans converted to single dose since 24 Gy achievable without exceeding OAR constraints

48 Focal HDR reports Hosni Radiother Oncol 2017 Constraints: D0.5 cc bladder/urethra <15 Gy RD2cc < 10.8 Gy Inserted catheters 11 (1-19) U;lized catheters 4 (1-12) GTV: 0.7 cc ( ) PTV: 5.6 cc (5.2-20) OAR doses UD0.5cc: 9.2 Gy (5.6-15) RD2cc: 9.4 Gy ( )

49 1 fraction plan 2 fraction plan Failed plan

50 Focal HDR protocol mpmri; iden;fica;on of DIL On T2, ADC and DCE Boolean addi;on of DIL s Contour prostate, urethra, DIL Pre- op TRUS with aerated gel in urethra Fuse mpmri and TRUS for transposi;on of DIL Rigid registra;on or deformable HDR procedure: fusion of intra- opera;ve TRUS with catheters in posi;on to pre- op TRUS with DIL Dose op;miza;on Treatment delivery

51 Summary:HDR focal brachytherapy Many advantages over other modali;es Dose precisely controlled and delivered No seed loss No organ mo;on No pa;ent mo;on Dose easily sculpted to target with avoidance of cri;cal structures Proven efficacy Can be whole gland with focussed boost, focal only, monotherapy or combined with EBRT

52 Defining success No validated PSA outcome Ac;ve monitoring similar to that for Ac;ve Surveillance Significant undetected disease Residual disease in the treated area Cancer progression Biopsy of treated and untreated areas mandatory Role for mpmri but requires further valida;on

53 Recommenda;ons: Focal Therapy Clinically significant disease in one area of the prostate op;mal Clinically insignificant disease monitored by AS Accurate localiza;on essen;al (mpmri and/or TTMB) Follow up and monitoring as per AS protocols including biopsy of treated and untreated areas Op;mal technology for focal therapy TBD Planning issues such as margin determina;on unsolved Level of evidence s;ll very low concerning disease control/survival