ICRU Recommendations

ICR RU recommedations on volume and dose David Sjöström,, Physicist Herlev Hospital,, Denmark

1

Backkground kground

Tumour cells T ll contained t i d in i the th red volume throughout the treatment course

Backkground kground

Tumour cells T ll contained t i d in i the th red volume throughout the treatment course

95% or more of the prescribed ib d dose d given i to t everything inside green area

Backkground kground

Tumour cells T ll contained t i d in i the th red volume throughout the treatment course

95% or more of the prescribed ib d dose d given i to t everything inside green area

How do we ensure that this picture reflects the reality of the treatment?

Backg ground Problem: We need the same definition ns of: - volume that has been treated - dose given to this volume - dose received by organs at risk

How to prescribe, record an nd report

Backg ground

ICRU Report No No.78 78 (2 2007)

Backg ground

Solution: ICRU reports - International recommendations for definittions of dose and volume in RT

Backg ground ICRU Report No.29 (1978) Dose specification for reportiing external beam therapy with “Dose photons and electrons” ICRU Report No No.50 50 (1993) “Prescribing, recording and re eporting photon beam therapy” (Superseded ICRU Repo ort No.29) ICRU Report No.62 (1999) “Supplement Supplement to ICRU Report No.50 N 50” No (Updated the ICRU Repo ort No.50 with some new concepts. p ICRU 50 still valid.) v )

Backg ground ICRU Report No.71 (2004) “Prescribing, recording and reportin ng electron beam therapy” (Extends concepts and recommenda ations from ICRU 50 and 62 from photons to electrons) ICRU Report No.78 (2007) “Prescribing, recording and reportin ng proton-beam therapy” ICRU Report No.83 (2010) “Prescribing, Recording and Reportiing intensity-modulated photon-beam therapy (IMRT)” (IMRT)

Volumes in IC CRU29 - 1978 “The Target Volume” The target volume consists of the tumours (if present) and any other tissue with presume ed tumour • expected movements of tissues containin ng the target volume • variations in shape and size of the target volume • variations in treatment set-up

+ Organs at risk whose presence influence treatment planning

Volumes Volumes 1978 ICRU29

“The Targett Volume”

Organs at risk

Volumes Why all these e updates? Improvements in staging and a imaging procedures Improvements in the delivery and a precision of radiotherapy more detailed and accurate set of defin nitions to maximize the benefit of the develop pment.

Volumes in IC CRU29 - 1978 Example p Target volume Primary + Boost “Treatment fields defined from anatomical land marks in 2D”

Computerised Tom mography (X Ray) Possible to define and delineate Outline of patient body Tumour Sensitive organs

Possible to Optimize how to irradiate

Volumes 1978 ICRU29

1993 ICRU50

“The Targett Volume”

Organs at risk

… a realization th hat better tools were needed …

Volumes in IC CRU50 - 1993 Gross Tumour Volume (GTV) The GTV is the gross demonstrable extent and location of the malignant growth. GTV consists of: primary tumour metastatic t t ti lymphnodes l h d other metastases

The demonstrated tumour

Volumes in IC CRU50 - 1993 Clinical Target Volume (CTV) The CTV is a tissue volume that contains a demonstrable GTV and/or subclinical, microscopical malignant disease. Suspected lymph nodes Suspected disease around GTV CTV = GTV (if there) + subclinical disease Cannott b C be d detected t t d - “subclinical”. “ b li i l” Based on clinical experience.

CTV I - GTV with margin margin, and CTV II – lymph nodes

Volumes in IC CRU50 - 1993 Planning Target Volume (PTV) The PTV is a geometrical concept Movements of tissues containing CTV Movements of patient Variations in size and shape Variations in beam geometry characteristic cs PTV = CTV + margin for geometrical variatiions Aid for treatment p planning; g; dose to PTV representing dose to CTV

CTV with margin forming the PTV

Volumes in IC CRU50 - 1993 CRU50

Volumes in IC CRU50 - 1993 Organs at risk The Organs at Risk are normal tissues who ose radiation sensitivity may significantly influence treatment planning and/or prescribed dose “Any Any possible movement of the organ at as s well as uncertainties in the set up must be considered”

Volumes in IC CRU50 - 1993 Treated Volume The Treated Volume is the volume which w receives at least the dose specified as being appropriate to ac chieve the purpose of the treatment.

Volumes in IC CRU50 - 1993 Irradiated Volume The Irradiated Volume is the volume e which receives a dose that is considered significant in relation to o normal tissue tolerance. tolerance

Volumes 1978 ICRU29

1993 ICRU50

“The Targett Volume”

GTV

CTV

PTV

Organs at risk

Organs at risk

Volumes 1978 ICRU29

“The Targett Volume”

CTV

PTV

Organs at risk

Organs at risk

1993 ICRU50

GTV

1999 ICRU62

… a lot of focus on o g geometrical variations in this time period… …

PROB BLEM

Structures within a body are not static

Positional variations CT before treatment

e.g. Physological processes Variations in filling of bladder and rectum

Positional variations CBCT first fraction

e.g. Physological processes Variations in filling of bladder and rectum

Positional variations Dose calculation CBCT

Concequenses Concequenses, underdosage of target or overdosage of OAR.

Positional variations

Organs and O d tumours t in i the th pelvis l i region i moves m mainly i l due d to t changes h in i the th digestive system and filling of bladder and rectum from day-to-day. Example: prostate, bladder, rectum, cervix. Mainly inter-fraction positional variation Typical values (1 SD) are 3 - 5 mm mm.

Breathing posit positional ional variations

Breathing positional variations

Breathing cycle (3-5 s) – during treatment (intra ( fraction variation) Movement of organs and tumours in the ab bdomen region. region Examples: lung tumours, kidneys, liver, breasts. Example: Diaphragm moves 1 - 4 cm underr normal free-breathing conditions conditions. For deep-breathing, the corresponding figure can c be 10 cm! Necessary to quantify organ motion individ dually for “curative” curative lung cancer patients

Breathing positional variations

Ekberg et al. Radiother Oncol 48: 71 71--77, 1998: 20 nsclc patients – organ motion measured with fluorroscopy Mean CTV movement with quiet re espiration: • 2.4 mm (med(med-lat lat)) • 2.4 mm (ant(ant-post) • 3.9 mm (sup(sup-inf inf)) Range (sup(sup-inf inf): ): 0 – 12 mm

Volumes in IC CRU62 - 1999 Internal Target Volume (ITV) CTV with margin added to compensate for expected e physiologic movements and variations in size shape and position of CTV V in relation to Internal Reference Point. ITV = CTV + IM (Internal Margin)

Internal reference point

New conceptts replacing ITV

Wolthaus et al al. Int. Int J J. Radiation Oncolo ogy Biol Biol. Phys 70 (4): 12291229-1238, 1238 2008

Mid ventilation (Time e averaged position)

Time avg avg.

Geometric avg.

Wolthaus et al. Int. J. Radiation Oncology Biol. Phys 64 (5): 15601560-1571, 2006

35

Summary o of problem

Extent of geometric variations: • abdomen target – mm to cm (iintra-fx amplitude) • pelvis target – a few mm (1 SD D inter-fx) inter fx)

Strategies g for dealing g with geom g metric variations in practice: p • breathing control • real-time tumour tracking • reproducible d ibl filling filli off bl bladder dd and d rectum t • Adaptive treatment

+ internal margin g (IM) ( )

Example brea athing control Expiration

Deep inspiration

Example a adaptation

Example H&N patient with tumour shrinkage/weight loss. Call for adaption?

PROB BLEM

Setting up the patient and the irradiation fields can not be done identically from day-to-day

High/Low dose area is moving when set-up of patient p is varying

Set-up variations

Vrt Lat Long Pitch Roll Rot

Set-up variations 30

Numb ber of settups

VRT LNG LAT 20

10

-0.5

0

Shift / [cm] [ ]

0.5

NSCLC setup W. Ottosson, M. Baker, M. Hedman, C.F Behren ns, D Sjöström “Evaluation of setup accuracy for NSCLC studying the impact of different types off cone-beam CT matches on whole thorax, columna vertibralis, and GTV” Acta Oncol. 2010 0; 49: 1184–1191

Set-up variations Population Setup Errors 1

Long.

2

Long.

Systematic

Vert.

Vert.

Standard Deviation



Pop p

3

Long.

4

V t Vert.

Long.

Random

V t Vert.

Standard Deviation



Pop

M (CTV  PTV )  2 .5  Pop  0 .7 Pop

Set-up Set up variations CTV to PTV margin m recipe

ICRU Report No.83 (2010)

Set-up variations σ Σ 0 • We need to know the magnittude of these “set-up variations” (Σset-up variations set up and σset-up set up).. • Σset-upp and σset-upp should be minimised. m • Remaining Σset-up and σset-up should s be taken into account. t

Volumes in IC CRU62 - 1999 Planning Target Volume (PTV) ITV with margin added to compensate fo or external geometric uncertainties in relation to External Reference Point. PTV = ITV + SM (Set-up Margin)

Internal reference point

External reference point

Summary o of problem

Extent of geometric variations: • often a few mm (1 SD inter-fx)

Strategies for dealing with geom metric variations in practice: • fixation • off-line portal imaging with de ecision rule protocols • on-line portal imaging • IGRT

+ set-up margin (SM)

E ample IGRT Example

Ottosson et al. “Evaluation of setup accuracy forr NSCLC studying the impact of different types of cone-beam CT matches on whole thorax, columna vertibralis, and GTV” Acta Oncol. 2010; 49: 1184–1191

Volumes in IC CRU62 - 1999 Organ at Risk (OR) Organs g at Risk are normal tissues whose w radiation sensitivity y may y significantly influence treatment pla anning and/or prescribed dose.

Volumes in IC CRU62 - 1999 Organ at Risk (OR) Organs g at Risk are normal tissues whose w radiation sensitivity y may y significantly influence treatment pla anning and/or prescribed dose.

Planning Organ at Risk Volume (PRV) The PRV is the OR with an integrate ed geometric margin added added, in analogue with the CTV-to-PTV expa ansion.

Volumes in ICRU62 - 1999 Conformity index Conformity index (CI) defined as the e quotient of the treated volume (TV) and the volume of PTV (CI = VTV 1). T /VPTV ≥ 1).

< Treated Volume

> Irradiated d Volume

Volumes 1978 ICRU29

“The Targett Volume”

1993 ICRU50

GTV

CTV

1999 ICRU62

GTV

CTV

Organs at risk

Organs at risk

PTV

ITV

PTV

OR

PRV

Volumes 1978 ICRU29

“The Targett Volume”

1993 ICRU50

GTV

CTV

1999 ICRU62

GTV

CTV

2004 ICRU71

Organs at risk

Organs at risk

PTV

ITV

PTV

OR

PRV

Volumes in IC CRU71 - 2004 Gross Tumour Volume (GTV) The GTV is the gross demonstrable extent and a location of the malignant growth. primary tumour – (GTV-T) metastatic regional node – (GTV (GTV-N) N) distant metastasis – (GTV-M)

Clinical Target Volume (CTV) The CTV is a tissue volume that contains a demonstrable GTV and/or subclinical,, microscopical malignant disease, which must be eliminated. CTV = GTV (if there) + subclinical disease (CTV T CTV-N, (CTV-T, CTV N CTV CTV-M) M)

Planning Target Volume (PTV) As above: PTV-T, PTV-N, PTV-M

Comparison between macroscopic and microscopic section of malign and benign breast tumor

ICRU Report No No.83 83 (2010)

Volumes 1978 ICRU29

“The Targett Volume”

Organs at risk

Organs at risk

1993 ICRU50

GTV

CTV

PTV

1999 ICRU62

GTV

CTV

ITV

PTV

OR

CTVCTV-T CTV--N CTV CTV CTV--M

(ITV)

2004 ICRU71

GTV-T GTVGTV--N GTV GTV--M GTV

PTVPTV-T PTV--N PTV PTV--M PTV

OAR

PRV

PRV

Volumes 1978 ICRU29

“The Targett Volume”

Organs at risk

Organs at risk

1993 ICRU50

GTV

CTV

1999 ICRU62

GTV

CTV

ITV

PTV

OR

CTVCTV-T CTV--N CTV CTV CTV--M

(ITV)

2004 ICRU71

GTV-T GTVGTV--N GTV GTV--M GTV

PTVPTV-T PTV--N PTV PTV--M PTV

OAR

…ICRU…

PTV

… variations i ti in i de delineation li ti … … a lot of work on n imaging … … “dose sculpting” is more readily done … … the “dose“dose-bath h” might be a problem …

PRV

PRV

PROB BLEM

Target-location might sh hift, depending on who is delinea ating it

Target-locatio on might shift, depending on wh ho is delineating it

Stenbakkers et al. Int J Ra adiat Oncol Biol Phys y 2005

Target-locatio on might shift, depending on wh ho is delineating it

KC Chao et al. Int J Radiat Oncol Biol Phys 68(5):2007

PROB BLEM Target-locatio T tl tion might i ht shift, hift depending on im maging modality

Target-location might sh hift, depending on who is delineating it and imaging modality

Stenbakkers et al. Int J Ra adiat Oncol Biol Phys y 2005

Target-locatio on might shift, depending on im maging modality

CT

Target-locatio on might shift, depending on im maging modality

MRI

Target-locatio on might shift, depending on im maging modality

CT

Target-locatio on might shift, depending on im maging modality

MRI

Target-locatio on might shift, depending on im maging modality

Charnley y et al. Britis sh J Radiology gy 2005

Summary o of problem

Extent of geometric variations: • Delineation variation the largest geometrrical variation in radiotherapy – often cm

Strategies for dealing with geom metric variations in practice:

• radiologists input in GTV delineation • use optimal imaging modalities • e.g. contrast • workshops/audits • Autocontouring (?)

ICRU: “The uncertainty in the delineation ((of GTV and CTV)) should be included in margin considerations”

Volumes in ICRU U78 and ICRU83

Definition of volumes depends on the imaging modality

ICRU: “A clear annotation has to t be used” e.g.

GTV-T (CT, 0 Gy)

GTV-T (MRI T2, fat sat, 0 Gy)

ICRU Report No.8 83 (2010)

GTV-T (FDG-PET, 0 Gy)

Volumes in ICRU U78 and ICRU83

Definition of volumes depends on when imaging is done

ICRU: “… recommended to indiicate the dose and/or the time when the GTV has been evaluatted/measured… ted/measured ”

GTV-T (CT, 20 Gy)

GTV-T (MRI T2,, fat sat, 20 Gy)

ICRU Report No.8 83 (2010)

GTV-T (FDG-PET, 20 Gy):

Volumes in ICRU U78 and ICRU83 Overlapping Volumes

Volumes in ICRU U78 and ICRU83 Overlapping Volumes and a buildup regions

ICRU Report No.83 N (2010)

Volumes in ICRU U78 and ICRU83

The PTV might overlap an adjac cent PRV or there might be other reasons to subdivide the PTV ICRU: “… the delineation of the PTV margins should not be compromised” “… subdivision of the PTV into regions with different ff prescribed doses (so-called PTV sub-volumes, PTVSV) may be used”

ICRU Report No.83 (2010)

Volumes in ICRU U78 and ICRU83 PTV extending outsid de body contour

ICRU Reporrt No.83 (2010)

Volumes in ICRU U78 and ICRU83

With new techniques, q , carcinogenesis g need ds to be monitored;; there might g also be unsuspected regions of high dose within the t patient

ICRU: “… The volume within the patient ex xcluding any delineated OAR and the CTV(s) should be identified as the “remain ning volume at risk” (RVR)”

Volumes 1978 ICRU29

“The Targett Volume”

Organs at risk

Organs at risk

1993 ICRU50

GTV

CTV V

1999 ICRU62

GTV

CTV V

ITV

PTV

OR

PRV

CTVCTV-T CTV--N CTV CTV--M CTV

(ITV)

2004 ICRU71

GTV-T GTVGTV--N GTV GTV--M GTV

PTV PTV--T PTV--N PTV PTV--M PTV

OAR

PRV

2007 ICRU78 2010 ICRU83

e.g e e.g. g. GTV--T (MR, 0 Gy GTV Gy)) GTV--T (CT, 0 Gy GTV Gy)) GTV--T (PET, 16 Gy GTV Gy)) GTV--TN (PET, 16 Gy) GTV GTV--N (MR, 16 Gy) GTV GTV--N (CT, 0 Gy) GTV

PTV

OAR PRV RVR MR, 0 Gy Gy)) (ITV) CTV-T (M CTVCTV--T (CT, 0 Gy) CTV Gy) CTV CTV--T (PET, 16 Gy Gy)) CTV CTV--TN (PET, 16 Gy) MR, 16 Gy) CTV CTV--N (M CTV CTV--N (C CT, 0 Gy)

PTV PTV--T (MR, 0 Gy Gy)) PTV--T (CT, 0 Gy PTV Gy)) PTVPTV-T (PET, 16 Gy Gy)) PTVPTV-TN (PET, 16 Gy) PTV PTV--N (MR, 16 Gy) PTVPTV-N (CT, 0 Gy)

Volumes – Do oes it matter?

Dirk Verelllen et al Nature Reviews Cancer 7, 949-960 9 (December 2007)

ICRU recommen ndations on Dose

Dose in ICRU5 50 and ICRU62 ICRU Referrence Point - The dose at the point should be clinically relevant - The point should be easy to define in a clea ar and unambiguous way - The point should be selected so that the dosse can be accurately determined - The point should be in a region where there e is no steep dose gradient In central part of PTV at intersection of beam axes!

Dose in ICRU5 50 and ICRU62 Level 1. Minimum lev vel of reporting p g dose - The dose at the ICRU Reference Poin nt - Maximum dose to the PTV (Dmax) - Minimum dose to the PTV (Dmin) - Maximum M i d dose tto th the OR/PRV OR/PRV:s

Dose in ICRU83 Level 1. Why is it not adequate today? t -The absorbed dose distribution for IMR RT can be less homogeneous then in CRT -Each beam can produce absorbed dosse with large dose gradients - Large dose gradients (10%/mm) in the e PTV boundary i.e. small shifts in delivery can affect the reliability of using a single e point to report the dose - Because modern TPS have evaluation n tools that makes it possible.

- Monte Carlo calculations have statisticcal fluctuation in the results for small volumes which makes it difficult and uncertain to determine an absorbed dose to a point.

Dose in ICRU83

Level of reporting for IMRT

Leval 2. Minimum level of reporrting dose in IMRT PTV and CTV -Report the DV, where “V” refers to a percentage p of volume covered by the specified dose, for each PTV and CTV V: -D95% (dose that covers 95% of the vo olume) -D50% (median dose) -Dmean (mean dose) -Dose near max: D2% -Dose near min: D98% OAR and PRV -Dmean (parallell organs) -D2% (serial organs) -V VD (Volume receiving more than e.g. 2 20 Gy). …AND… -State State the treatment planning system a and algorithm used for planning and delivery system

Dose in ICRU83 Leval 2. Minimum level of reportting dose in IMRT PTV and CTV %

D2% ”close to max” replaces Dmax

100

D50% = Dmedian Dmean

OAR and PRV

Volume V

D98% ”close to min” replaces Dmin

VD (e.g volume receiving more than 50 Gy)

75

50

25

V50Gy (parallel organs) Dmean (parallel organs)

25

50

Dose D

75

100

Gy

D2% (serial organs)

…AND… -State the treatment planning syste em and algorithm used for planning and delivery system used for treatm ment

Dose in ICRU83 Reporting of absorbed a dose Why not D100% and D0%(the earrlier definition of min and max absorbed dose)? E.g. PTV of 0.5 litres (radius 49.2 mm). radius changed by less than 0.2 mm => 1% change in volume D98% and D2% serve the purpose to rep port an absorbed dose that is not reliant on a single computation point.

Dose in ICRU83 Reporting of absorbed a dose

Median ed a abso absorbed bed dose ((D50) is s likely e y to be a g good measure easu e of o a typ typical ca abso absorbed bed dose in a relatively homogeneo ously irradiated tumor

ICRU Report No.83 (2010)

Dose in ICRU83 Reporting of absorbed dose Why D50 50% %?

Deviation between prescribed and planned absorbed a doses for 803 patients. The median absorbed dose (D50) is th he most accurate quantity ICRU Report No.83 (2010)

Dose in ICRU83 Reporting of absorbed dose

Example p of two different approach pp es to p prescribe the dose ((assuming g that D50 corresponds to the ICRU refere ence point). ICRU Report No.83 (2010)

Dose in ICRU83 Level of reporting for IMRT Leval 3. 3 Techniques and concep pts that are under development -Dose Homogeneity characterizes h t i th the uniformity if it off the th absorbed ab b d d dose di distribution t ib ti within ithi th the target -Dose D C Conformity f it characterizes the degree to which the t high dose region conforms to the target volume -Clinical and Biological evaluation (e.g.. TCP, NTCP, EUD) -Confidence C f interval (e.g. ( including sysstematic and random uncertainties))

Dose in ICRU83 Dose Homogeneity y and Dose Conformity

Homogeneity Index

ICRU Report No. 83 (2010)

Dose in ICRU83 Dose Homogeneity y and Dose Conformity

Loic Feuvret et al. Int. J. Radiation Oncology Biol. Phys., 64 (2) 2006

Conformity index = 1

Dose in ICRU83 Dose Homogeneity y and Dose Conformity

Loic Feuvret et al al. Int. J. Radiation Oncology Biol. Phys., 64 (2) 2006

Dose in ICRU83 Quality assurance for IMRT treatment plans Previous 5% point dose accuracy specification

Replaced by volumetric dose ac ccuracy specification for IMRT Not limited to single point High gradient (≥20%/cm):85% of points p within 5 mm (1 SD of 3.5 mm)) Low gradient (