Luca Guerra – Federica Elisei

Medicina Nucleare – Centro di Bioimmagini Molecolari

Ospedale San Gerardo - Monza

Università degli Studi Milano - Bicocca

Metabolic Imaging in Radiation Treatment Planning (RTP)

The possibility to detect the metabolic activation of a lesion has generated interesting perspectives in radiation treatment planning, including

Detection of lesions unsuspected on anatomical imaging

Prevention of futile irradiation of lesion without metabolism activation

Identification of subvolume eligible for boost dose (dose painting)

Modelling the target volume in function of the response to treatment (response adapted therapy)

Baum RP et al. Quat J Nucl Med Mol Imaging 2004; 48:119-142Weber WA et al. Eur J Nucl Med Mol Imaging 2006; 33; (suppl.1):27-37Ling CC et al. Med Phys 2005; 32:2189-2192

BTV or GTVPET

Target volume obtained by contouring biological characteristics of a lesion where radiopharmaceuticals specific for a metabolic process are accumulated (glucose metabolism, hypoxia, membrane synthesis, nucleotide synthesis and others)

IMAGE SEGMENTATION METHODSIMAGE SEGMENTATION METHODS• Manual contouring

• Thresholding with respect to SUVmax

• Thresholding with respect to Lesion activity

• Thresholding with respect to L/B ratio (adaptive)

• Others………….

GTVPET delineation

H Reggio Emilia

Manual ContouringManual ContouringVisual based segmentationExpertise needed

GTVPET delineation

More homogeneous and converging BTV data with standardized visual protocol of segmentationMacManus MP et al. Int J Radiat Oncol Biol Phys 2007; 69:S154 (abst)Leong T et al. Radiot Oncol 2006; 78:254-261

Even when using standardized contouring protocols, variability between observers may be present Potzsch C et al. Nuklearmedizine 2006; 45:A42

Threshold with respect to Threshold with respect to SUVSUVmaxmaxUsually an absolute SUVmax of 2.5-3.0 is acceptedBlack QC et al. Int J Radiat Oncol Biol Phys 2004; 60:1272-1282

Hong R et al. Int J Radiat Oncol Biol Phys 2007; 67:720-726

SUVmax is not an indicator of malignancy and is affected by many factors

GTVPET delineation

SUV = 2.5SUV = 2.5

H Reggio Emilia

Lesion movement

Partial volume effect

Uptake time

Blood glucose

Body weight

Physiological activity

Threshold with respect to lesion activityThreshold with respect to lesion activity

Usually ~ 40% is accepted (Erdi YE et al. Cancer 1997; 80:2505-9)

GTVPET delineation

• Threshold variation with respect to the sphere volume and contrast

• Best volume prediction with a fixed threshold between 36% and 44% of the maximum, only for lesions with a volume larger than 4 ml.

• A priori knowledge of the volume lesion • Non-homogeneous uptake inside the target

H Reggio Emilia

Nestle U et al. J Nucl Med 2005; 46:1342-8

Yaremoko B et al. Nucl Med Commun 2005;26:433-40

Threshold with respect to Threshold with respect to lesion/background activity ratio (Adaptive)lesion/background activity ratio (Adaptive)

GTVPET delineation

Cylindrical phantom with spheres (Vol: 0.55-17.15 ml)

*Van Baardwjik et al. Int J Radiat Oncol Biol Phys 2007; 68:771-8

• Applications to head and neck

studies with better results in

comparison to other anatomical

methods

• Applicable to low activity lesion

• Reduction of IOV

• Good correlation with pathologic

tumor diameter in NSCLC *

Correlation coefficient = 0.90; r2=0.82

Geets X et al. Eur J Nucl Med Mol Imaging 2007; 34:1427-38Geets X et al. Radiother Oncol 2004; 71:267-273 Daisne JF et al. Radiat Oncol 2003;69:247-250

• LESION HETEROGENEITY

• BACKGROUND HETEROGENEITY

• ….

THRESHOLD SEGMENTATION METHODS:OTHER ISSUES

Max = 24,5 kBq/mlMax = 16 kBq/ml

HSR - Milan

• LESION HETEROGENEITY

• BACKGROUND HETEROGENEITY

• ….

THRESHOLD SEGMENTATION METHODS:OTHER ISSUES

LESION Th1(%) Th2(%)

B1B2

HSR - Milan

BACKGROUND ETHEROGENEITY

CT PETHSR Milan

• L/B chest wall = 5.7 -- Th 35%• L/B lung = 18.9 -- Th 18%

• final contour

BACKGROUND ETHEROGENEITY

CT PETHSR Milan

Other algorithms for GTVPET delineation

Brambilla M et al Med Phys. 2008 Apr;35(4):1207-13

Iterative thresholding algorithm: threshold is found iteratively on a slice by slice analysis

Jentzen M et al. J Nucl Med. 2007;48:108-14Drever L et al. Med Phys. 2007;34:1253-65

Gradient based contouring algorithm: segmentation is neither sensitive to heterogeneity uptake of the tumor, nor to background variations

Geetz X et al. Eur J Nucl Med Mol Imaging 2007; 34:1427-1438Graves EE et al. Technol Cancer Res Treat 2007; 6:111-121

EsESDBmmsphereIDB

MBqABBratioT

BBTH acq

+×+×+

×+−×+=

)()(

)()/

11((%)

43

210

Do we have the optimal segmentation?

The availability of multiple automated methods for contouring tumors and the absence of any reliable intercomparison make it difficult to recommend any single technique.

….when an automated method gives a result that looks plausible, we accept it. When it does not, we can adjust the parameters and try again or edit the automated contour manually. What is the reference standard then? It is, for now, the opinion of the treating radiation oncologist, who signs the treatment prescription plan.

What do I do now?Collect as much clinical data as possible

Perform a PET/CT focused on treatment planning (count statistics, patient positioning, PET and CT coregistration...)

Define the presence and location of disease on PET/CT

Use the automatic algorithm you prefer for segmentation

Check the GTVPET slice by slice and refine it manually, if you think it is needed

Review and discuss (once, twice or more..) your results with theRadiation Oncologist

PET in RTP of NSCLC

Radiation treatment of NSCLC is an essential step of cure, including neoadjuvant and adjuvant finality

The best probability of disease control is obtained when the patient is accurately selected for RTP and the dose is maximised to the target

Should 18F-FDG PET/CT be routinely included in the staging workup of NSCLC before RT planning?

Metabolic Imaging is widely used for staging and restaging NSCLC

Higher accuracy in comparison to anatomical imaging in detectingnodal involvement and distant metastases

Impact on patients management

PET in NSCLC patient management

35%

21%

Futile thoracotomiesCI+PET

52%Fisher B et al.

N Engl J Med 2009; 361:302-309

41%Van Tinteren et al.

Lancet 2002; 359:1388-1393

Futile thoracotomiesCI alone

Two randomised prospective trials (more than 180 pts enrolled in each

study) comparing staging of NSCLC with and without PET and the

impact on pts management in terms of inappropriate thoracotomies

Better N and M staging than CI

Change in planning treatment (modification of GTV/PTV)

Exclusion from treatment (up to 30%)MacManus M et al. Cancer 2001; 92:886-895MacManus M et al. Int J Radiat Oncol Biol Phys 2002; 52;351-361Chapman JD et al. Int J Rad Oncol Biol Phys 2003; 55:294-301MacManus M et al. Radioth Oncol 2009; 91;85-94

PET in RT planning of NSCLCShould 18F-FDG PET/CT be routinely included in the staging workup of NSCLC before RT planning?

PET/CT e RADIOTERAPIAPET/CT e RADIOTERAPIA

Greco et al Lung Cancer 2007

PET in RT planning of NSCLC

LYMPH-NODES (D< 10 mm)ATELECTASIS

VIABLE TUMOR

HSR - Milan

CT PET/CT

CT-based TT PET/CT-based TT

TOMOTHERAPYTREATMENT

PLAN

HSR Milano

PET/CT and RTP

Change in planning treatment (modification of GTV/PTV)

Exclusion from treatment (up to 30%)MacManus M et al. Cancer 2001; 92:886-895MacManus M et al. Int J Radiat Oncol Biol Phys 2002; 52;351-361Chapman JD et al. Int J Rad Oncol Biol Phys 2003; 55:294-301MacManus M et al. Radioth Oncol 2009; 91;85-94

PET in RT planning of NSCLCShould 18F-FDG PET/CT be routinely included in the staging workup of NSCLC before RT planning?

PET in RT planning of NSCLC

339196 NSCLC staging – bone metastases at PET/CT not diagnosed at ceCT; MRI confirmation

HSG - Monza

Increasing the OS of pts staged with PET before RT

PET in RT planning of NSCLC

HR PET vs NoPET pts 0.49 (p=0.0016)

MacManus M et al. Int J Radiat Oncol Biol Phys 2002; 52:351-361

Does staging PET/CT pre-RTP impact on pts outcome?

PET in RT planning of NSCLC

•Yes, PET imaging should be

included routinely in the staging

work-up before treatment

A summary of PET in RT planning

124658GTVCLEARTh 40%SwLung24Bradley 2004

-6060GTVTh 50%SwH/N6Scarfone 2004

5721

4321

10042

GTVPTV

VisualNoneEsoph.14Vrieze 2004

Hw

Sw

Sw

Sw

None

Sw

Sw

Visual

Visual

Visual

Graphical

PET/CTfusion

GTV>25%

PTV>20%

GTV

PTV

PTV

GTV

GTV>5mm

Rad field

GTV

Rad field

Rad field

Rad Field

Parameter

4753100Th 50%Lung30Caldwell 2001

162238NoneLung102Mac Manus 2001

402262NoneLung73Vanuystel 2000

10-5010-20

89

100

100

33

35

> 34

27

% PTs withvariation

5

64

30-76

33

9

34

27

↑ %

5

36

24-70

-

26

nq

-

↓ %

VisualH/N21Nishioka 2002

Th 50% (max-bkg)Sev39Ciernik 2003

Th 42%Lung11Erdi 2002

Th 50%Lung23Mah 2002

Th 40%Lung12Giraud 2001

NoneLung34Nestle 1998

VisualLung35Munley 1999

NoneLung -LN15Kiffer 1998

Segmentationmethod

TumourPTsAuthors

Modified from M. MacManus et al. Radiother Oncol 2009; 91:85-94

A summary of PET in RT planning

362763GTVTh 50%SwLung11Spratt 2010

937100GTVTh 42%HwMesoth13Pehlivan 2010

40GTVIterativeSwH/N9Henriquez 2009

72333GTVVisualSwHD30Hutchings 2007

88GTVVisualSwH/N28Wang 2006

6986GTVVisualSwEsoph21Leong 2006

56GTVnanaAnal ca27Krengli 2010 Epub ahaed of print

144357GTVVisualSwEsoph21Muijs 2009

163955GTV>25%Th 40-50%SwLung18Messa 2005

Sw

Sw

Hw

Hw

PET/CTfusion

GTV>25%

GTV

GTV

GTV

Parameter

552VisualLung19Ashamalla 2005

242148VisualLung92Deniaud-Alexandre 2005

352156VisualEsoph130Moureau-Zabatto 2005

751893Th 50%H/N40Paulino 2005

% PTs withvariation

↑ % ↓ % Segmentation

methodTumourPTsAuthors

333164Mainly GTVvariousvariousvarious898TOTAL

Modified from M. MacManus et al. Radiother Oncol 2009; 91:85:94

In Conclusion

….. You can choose to continue to believe in something you think to be real…….

… or to see how much is real BTV

Thank you for your attention

I believe BTV to be a real thing…..