External Beam RT for Prostate Cancer - ASTRO

External Beam RT for Prostate Cancer 

Andrew K. Lee, MD, MPH 

Associate Professor 

M.D. Anderson Cancer Center

Disclosure 

• I have no relevant conflicts of interest to 

disclose. 

• This presentation will NOT discuss 

iinvestigational i i l or off-label ff l b l use of fddrugs 

or 

therapies.

Learning Objectives 

• Understand the basics of simulating and 

planning a patient for prostate cancer 

radiation therapy 

• UUnderstand d d the h methods h d ffor appropriate i 

delivery of dose-escalated and image-guided 

therapy h iin 

prostate cancer

Localized prostate cancer 

Low risk 

T1-2 T1 2 

Gleason 6 

PSA 20 

EBRT + HT 

EBRT + Brachy +HT 

Surgery (select)

2010 AJCC Staging/Prognostic GROUPS 

7th 7 Edition 

• Group I (Low risk) 

T1 T1a-2a, 2 Gleason Gl 66, PSA

MDACC prostate EBRT recommendations 

• Low risk 78 Gy (2 Gy)PTV Gy) PTV 

(>80 Gy CTV) 

• Intermediate risk Prostate & “proximal” SV 

6mo HT for select pts 

(2 mos TAB then leuprolide alone) 

• High risk & T3 Prostate & most of SV 

(Select pts LN) 

2 years HT

Dose-escalation Dose escalation w/ less toxicity 

• Delivery y techniques q 

– IMRT/ VMAT 

– Protons 

• Reduce PTV 

– Target localization (e.g. IGRT) 

– Target g immobilzation (e.g. ( g rectal balloon) ) 

– Reduce CTV 

• Selective dose-escalation

At simulation… 

minimize systematic errors 

• If using fiducials: ≥3 fiducials ≥5 days prior to sim 

– If you cannot wait 5 days, then consider verification CT (CT or CBCT) 

the first week of treatment 

• Comfortably semi-full semi full bladder (do NOT overfill) 

• Not overly distended rectum (+/- enema) 

• Supine 

• Leg immobilization 

• Make sure patient is relaxed 

• Scan from L5 through lesser trochanters 

• 2-3 mm slices (make sure TPS can expand PTV correctly w/ 

chosen slice thickness)

Systematic errors are clinically relevant

PSA control by mean rectal 

Cross Sectional Area at simulation

• Impact of rectal 

distention may be 

more significant than 

risk group

Take home message 

Do not miss posterior aspect of prostate! 

>2/3 cancers arise in peripheral zone 

Si Simulate l t with ith empty t rectum t ( (e.g. enema) ) 

Thi d h f i i i l 

This decreases chances of missing posteriorly 

regardless of PTV

• Rectum 

• Bladder l dd 

• Femoral heads 

• CTV 

Defining Structures 

– Low risk = Prostate only 

– IInt risk ik= PProstate + prox SV 

– High risk = Prostate (+EPE) + SV (+/- nodes) 

• Use zoom 

• Use window and level 

• Use other planes of view (especially sag for apex)

Don’t forget to window-level 

HHelps l w/ / ddefining fi i ti tissue planes l 

Pelvic W/L Head W/L

Urogenital diaghragm 

insertion into symphysis 

NOTE: Do NOT under-contour apex. 

Almost all PZ, no capsule, common site for RT 

failures failures. 

In very advanced cases, disease can track along 

membranous urethra.

Defining Organs at Risk (OAR) 

Avoidance structures and denominator for DVH 

• RECTUM: 

From inferior ischium to anterior flexion of sigmoid 

Alt Alternatively ti l can use li linear llength th of f 10 10-11cm 11 

• BLADDER: 

Entire bladder (interpolate contour) 

• FEMORAL HEADS: 

Entire femoral head to lesser trochanter

Rectum and Bladder 

• Want to contour the rectum- rectum not the peri- peri 

rectal muscles. 

• If you using ultrasound-based guidance, pay 

special i l attention i to bl bladder-prostate 

dd 

interface. 

– Also will need to contour non-CTV portion of SV’s 

as reference structure

Ultrasound Alignment (sagittal)

IGRT PTV: VOLUMETRICALLY expand CTV 5-7 mm except 

posteriorly 4-5mm. 

Review PTV prior to planning. Validate PTV margin for your clinic. 

Current MDACC technique is 78Gy (2Gy) prescribed to PTV

MDACC DVH Plan Evaluation: Clinical Constraints 

(Clinical constraints ≠ Planning parameters) 

PTV: >96%V @ 78Gy 

Prostate: 100%V @ @ 78Gy 

SV: >98%V @ 78Gy 

Rectum:

8 angles for virtually any anatomy w/ 6 MV 

U Use

MDACC IMRT planning method 

• Use series of avoidance structures or “rings” in addition 

to iindividual di id l organs 

• Conformal plans with “compact” dose distributions 

• Fewer trials are needed 

• 8 beam angles or VMAT 

• Minimize total monitor units 

• Fewer beam segments

OAR and Objectives 

External 

Ring 2 

Ring 1 

Prostate + SV 

Max Dose 3800 cGy 


Max DVH 7500 2% 


Uniform Dose7800 cGy

ROI Objectives (IMRT) 

ROI Type Target cGy % Volume Weight 

Prostate + SV Uniform Dose 7760 100 

Prostate + SV Max Dose 8000 20 

Rectum Max DVH 6000 10% 1 



Bladder Max DVH 6000 8% 1 



Ring 1 Max DVH 7500 2% 10 

Ring 2 Max Dose 5500 5 

Ring 2 Max DVH 3000 25% 1 

External Max Dose 3800 50

DVH Plan Evaluation: Clinical Constraints 

(Clinical constraints ≠ Planning parameters) 

( gp ) 

Prostate: 

>100%V@78Gy 

>100%V@78Gy 

100%V@78Gy 

SV: 

>98%V@78Gy 

Rectum: 

Axial dose distribution 

(qualitative evaluation)

Sagittal g 

dose distribution

Minimum dose vs. Mean dose 

• >96% PTV receives ≥ 78 Gy 

• 100% CTV receives ≥78 Gy 

• Mean dose to prostate ≈ 80-81 Gy 

• Need to have threshold for heterogeneity 

Typically prescribe to >96% of mean dose

VMAT for prostate 

• Similar to IMRT for inverse planning 

• 2 arcs (clockwise then counter) 

• Gantry angles 210-150 °, 150-210 ° 

– May y extend to 182-178 °, , 178-182 ° for LN cases 

• 6MV 

• Avoid 0° 0 collimators to reduce “tongue tongue & groove effect effect” of 

MLC 

– Usually 10-45° but rotated in opposite directions for 2 nd arc (e.g. 15 vs. 335 °) 

• Avoid couch kicks unless absolutely needed 

• Typically start w/ 10x10 cm field 

• WWatch t h ttotal t l MU’ MU’s (96% mean

Use complementary angles for 

collimation for arc 1 vs. arc 2

VMAT

For both IMRT and VMAT 

• Monitor patients w/ large pannus 

• Have patient i centered d on table bl ffor sim i and d 

treatment 

• Consider couch for planning p g and if not using g 

IGRT (carbon fiber) couch, bring rails in to 

avoid treating g through g 

them

Rails “in” in and patient centered

Rails “IN” s “OUT” co ld change deli ered 

Rails “IN” vs. “OUT” could change delivered 

dose by 2.6% dose for IMRT and 2.1% VMAT

K. Pulliam et al. Phy Med Biol 56 (2011)

Sharp dose-fall off with IMRT and especially VMAT requires 

careful f l and d accurate t DAILY ttarget t llocalization li ti

Reducing PTV through IGRT 

(Image Guided Radiation Therapy) 

• RRequires i ddaily il iimaging i of fth the ttarget t 

• De Decrease rease “ssystematic stemati” set setup p error 

– From simulation to treatment 

• Correct for INTER-fractional movement 

– Pelvis 

– Rectal and bladder filling 

• May not account for INTRA-fractional movement

• Portal imaging 

• Ultrasound 

IGRT 

• Fiducial markers (intraprostatic) 

• Volumetric on-board imaging 

– In-room CT 

– Cone-beam CT

Ultrasound is reasonably accurate. 

• PTV margins must still be 

employed! 

– 5 mm may be b enoughh 

• Careful contouring of 

bladder/prostate interface 

• Thinner patients easier 

• Therapists training and 

feedback important 

• Patient training and 

cooperation ti are important i t t (e.g. ( 

bladder filling)

• Pros 

Ultrasound-based Ultrasound based alignment 

– Non-invasive 

– Reasonably good 

alignment 

– Visualize SV/ bladder 

– Visualize prostate 

surface contour 

• Cons 

– User-subjectivity 

– Patient anatomy may 

affect image quality 

– Impact of probe pressure 

on prostate position 

– Different imaging g g 

modality

Fiducial markers

Fiducial markers should form a triangle in each dimension 

around the isocenter if possible 

Coronal Sagittal-2 options 

Left Right 

Fiducial markers should be >2mm away y from pprostate capsule, p 

urethra, SV.

Fiducials: MV vs vs. KV imaging 

• Most systems using 

• KV imaging g gless 

dose 

• 2D-2D matching 

MV calculate center of 

mass shift 

– Increased dose to 

patient 

– NNeed d to t incorporate 

i t 

daily MV dose 

– Easy 

– Allows use of 2 fiducial 

markers 

– Error 1-2mm 

• Can use smaller fiducials or 

non non-metallic metallic 

– Decrease CT artifacts at 

simulation

EPID based fiducial alignment 

AP and d RRt LLateral l

AP kV radiograph (>300 lb pt) 

Thanks to R. Kudchadker 

DRR kV 

Fiducials

Problem w/ gold

Alternative markers 

Ca ++ vs. Carbon-coated ZrO 2

Pros: 

Fiducial-based alignment 

– Less subjectivity 

– Good alignment 

– Allows target tracking 

– Better for large patients 

– Image fusion (e.g. MRI- 

CT) 

– Visualize rectal gas 

Cons: 

– Invasive 

– Daily 

– Fiducials may migrate 

– No oimage age of o SV, S , rectum/bladder 

ec u /b adde 

– No image of prostate surface 

contour 

– Shifts may not be representative of 

volume 

– Fiducial markers may not stay in 

prostate 

MDACC study comparing fiducials vs CT on rails: 

MDACC study comparing fiducials vs CT-on-rails: 

1=U/S guidance, 2 (base-apex)=90%, 3=best 

(IJROBP 2009, 74)

• Better dose delivery => Better bullet 

• Better targeting => Better aim 

• Leads to smaller treatment margins 

– Lower toxicity for a given dose 

– Minimize toxicity at higher doses

Still need adequate PTV with 

fid fiducials…especially i l i ll ffor arc RT 

• Study d of f238 men treated d 5/2000-11/2004 

/ / 

• 70-78 Gy 

• 25 treated w/ fiducials &arcRT & arc RT 

• 5-y 5 y FFBF: 58% w/ / fiducials duc a s vs. s 9 91% % w/bone /bo eaalign g (p=0.02)! (p 0 0 ) 

– Multivariable analysis: Worse for fiducials p=0.047 

– 4 & 3mm PTV expansion may have been too tight 

Engels. IJROBP 2009

Intra-fraction Intra fraction variation due to gas 

IJROBP 2007

Gas may migrate 

superiorly! 

Note change in 

rectum, bladder, and 

prostate (translation, (translation 

rotation) 

IJROBP 2007

Fiducials vs. MRI 

Maximum prostate p deformations after translational matching gof 

fiducials: 6 mm x-direction, 13 mm in y, 7 mm in z 

[Nichol et al. IJROBP 67, 2007]

Prostate alignment does not guarantee SV alignment 

[Frank et al. IJROBP 71, 2008]

Larger margin needed to cover SV’s 

5mm margin will 

miss SV almost 30% 

of the time

Reduce PTV 

• Decrease inter and intra-fractional variation (not 

just j motion) ) 

• Pro-actively minimizes anatomic distortion 

– Control the prostate-rectal interface!! 

• Typical IGRT does not guarantee SV coverage or 

account for changes in contour deformation 

• PTV’s ≤3mm not optimal w/ standard IGRT alone

What we don’t like to see

ERB gives margin 

Do not need to rely on bladder filling

May need to re-define “adequate” PTV coverage 

(Don’t (Don t pump in more monitor units than you need) 

Remember Remember…building b ilding up p dose in air is diffic difficult! 

lt!

Water-filled Water filled ERB

Is there a way to increase therapeutic 

ratio w/ out increasing RT dose?

RCT: 70Gy vs 70Gy+HT 

D’A D’Amico i et al. l JAMA 292 292; 2004

Combined RT + HT 

• Intermediate risk 

– High dose RT alone (> 75Gy) 

– RT + “short-term” HT (4-6 months) 

• High risk 

– RT + “long-term” HT (>28 months) 

– RT+ “short-term” HT in select patients 

• Locally-advanced (T3+) 

– RT + “long-term” HT

Practical considerations of HT + RT 

• Begin HT at least 2 mos prior to RT 

– Leuprolide (LHRH agonist) or goserelin (GnRH agonist) 

– Bicalutamide (androgen receptor blocker) 

– If high AUA-SI, then start bicalutamide >2 weeks prior & consider 

adding alpha blocker (e.g. Flomax, Uroxatral, Rapaflo) 

• Total androgen blockade prior to RT 

– Prostate volume may reduce >30% in first 2-3 months 

– Total androgen blockade results in faster volume reduction than 

LHRH agonist i t monotherapy th 

– Want stable target volume through radiation course, decrease 

dose to rectum 

• Consider pre-HT planning target volume for patients with locallyadvanced 

(T3) disease 

– Prostate volume reduction may be concentric but tumor 

regression may not be 

– Neoadjuvant HT studies prior to RP

Axial Sagittal Coronal 

Pre-HT 

volume 

Post-HT 

volume

MDACC EBRT recommendations 

• Low risk Prostate only 

78 Gy PTV (>80 Gy CTV) 

• Intermediate risk Prostate & “Proximal” Proximal SV 

6 mo HT for select pts 

(≥ 2 mos TAB then leuprolide) 

• High risk & T3 Prostate & most of SV 

(Select pts LN) 

2 years HT

Decreasing “systematic” setup error from 

simulation to treatment is over half the battle 

• At simulation: Goal is reproducible anatomy 

– Comfortable position (a relaxed patient is a stable patient) 

– Empty rectum (allows use of tighter posterior margin) 

– Do not overfill bladder 

– Consider possible CT “table sag” 

• During treatment: Be proactive 

– Educate patients about bladder and rectal filling (give 

feedback) 

– IGRT primarily for translational rather than rotational shifts 

– Examine large variations

Proton therapy for Prostate Ca 

• Supine 

• ER Balloon 

MDACC ttechnique h i 

• Bony and d fid fiducial i l alignment li 

• 2-fields every day (opposed lats) 

• CTV = Prostate + proximal SV 

• 2CGEx39= 2 CGE x 39 78 CGE to “PTV” PTV 

• Mean dose to CTV ~81 CGE

Range depends on radiologic path length

Dancing prostate & hips using vacuum bag 

25 treatment CTs 

Acquired during a course 

of 42 fxs treatment 

Dong (MDA), 2002

• Immobilization and reproducible setup is 

important for protons just like IMRT 

• Reproduce radiologic path length 

• “Pro-active” target localization

Rectal balloon 

Sagittal and Coronal 

Fiducial marker 

Prostate 

Fiducial marker

Fiducial marker Fiducial marker

Newhauser et al: Dose Perturbations from Au Cylinders 

z / mm m 

10 

20 

30 

40 

-20 -10 0 

x / mm 

10 20

All 3 large fiducials to 3000 HU No fiducials (over-ridden to tissue density)

Ca ++ Ca vs vs. Carbon Carbon-coated coated ZrO 2

Carbon-coated Carbon coated Zr0 on kV 

2

Fusion at simulation between 

scan 1 and d 2 

Scan 2 Scan 1 

No need for verification plan

Planning parameters 

• Right & left lateral beams (daily) 

– IImproved dconformality f lit 

– Potentially more forgiving and robust 

• Geometrically and biologically (RBE) 

– Trade off is patient throughout 

• 78 CGE (2 CGE/fxn) to 100% CTV+margin 

– Usually prescribe to 98-96% isodose line 

• CTV = Prostate + Proximal SV

• Setup uncertainty ≤5mm 

• Distal margin = (0.035 x distal CTV 

radiological depth) + (3mm)* (3mm) 

• Proximal margin ~ 1cm 

• Smear ~0.9 0.9 cm 

(*Beam ( Beam range uncertainty)

• LM = setup uncertainty + 

penumbra p 

Lateral Margin 

• Setup uncertainty = 0.5cm 

• 225-250 225 250 MeV beam penumbra 

(95-50%) = 1.0-1.2cm 

• LM = 1.2-1.7 cm

Two opposed lateral beams

Rectal DVH V70=10%

Patient alignment 

at PTC-H 

• Daily yorthogonal g kV images g to 

align bony anatomy with 

reference DRR’s using 2-D 

matching 

X-ray tubes 

Image receptors 

Positioning Image Analysis System, ‘PIAS’ 

Hitachi

Take home points 

• Higher radiation doses yield higher PSA control rates 

• Do not use too tight of a margin 

• Proactively position the patient and target 

– Mi Minimize i i iinter- t and diintra-fraction t f ti variation i ti 

• Opposed lateral beams are relatively forgiving 

• Do not treat more of seminal vesicles than needed

External Beam RT for Prostate Cancer - ASTRO

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