Functional Imaging with PET for Sarcoma

Rodney Hicks, MD, FRACP

Director, Centre for Molecular Imaging

Guy Toner, MD, FRACP

Director, Medical Oncology

The Peter MacCallum Cancer Centre, Melbourne, Australia

Functional Imaging with PET in Sarcoma

Potential Applications

• Benign versus malignant

• Grading

• Biopsy guidance

• Staging

• Therapeutic monitoring

• Restaging ( local recurrence)

Functional Imaging with PET in Sarcoma

Potential Applications

• Benign versus malignant

• Grading

• Biopsy guidance

• Staging

• Therapeutic monitoring

• Restaging ( local recurrence)

Folpe AL et al. Clin Cancer Res 2000; 6: 1279-1287

Grade vs SUV (By percentile)

n = 89

25% 50% 75%

BEN 1.5 3.8 6.9

G1 1.55 2.65 4.11

G2 3.40 6.05 10.25

G3 4.22 6.85 19.35

PET in SarcomaApplications – Tumour Grading

• Right gluteal malignant fibrous histiocytoma

• Very high SUV

• Widely disseminated metastases at 12 months

PET in SarcomaApplications – Tumour Grading

p7003s0

• Pelvic spindle cell sarcoma

• Neoadjuvant Rx then resected at 3 months

• No recurrence at 12 months

p6694s0

PET in SarcomaApplications – Tumour Grading

Functional Imaging with PET in Sarcoma

Potential Applications

• Benign versus malignant

• Grading

• Biopsy guidance

• Staging

• Therapeutic monitoring

• Restaging ( local recurrence)

• Large left thigh mass with MRI features consistent with liposarcoma

• Biopsy guided to highest metabolic region confirmed high grade tumour

• Multiple subcutaneous metastases also detected by PET

PET in SarcomaApplications – Biopsy Guidance

p6826s0

Functional Imaging with PET in Sarcoma

Potential Applications

• Benign versus malignant

• Grading

• Biopsy guidance

• Staging

• Therapeutic monitoring

• Restaging ( local recurrence)

1. Franzius C et al Ann Oncol 2001; 12:479-486

2. Lucas JD et al J Bone Joint Surg Br 1998; 80:441-447

3. Franzius C et al Eur J Nucl Med 2000; 27:1305-1311

PET in SarcomaApplications - Staging

• CT is superior to stand-alone FDG PET for detecting lung mets (1,2)

• PET can identify false positive CT masses

• NPV is proportional to uptake in primary tumor

• FDG PET has higher sensitivity than CT for soft tissue metastases (2)

• Whole-body FDG PET may be superior to bone scan for bone metastases (3)

Franzius C et al Ann Oncol 2002;13:157-160

Garcia R et al J Nucl Med 1996; 37:1476-1479

el Zeftawy H et al Cancer Biother Radiopharm 2001; 16:37-46

Bredella M et al AJR 2002; 179:1145-1150

Johnson GR et al Clin Nucl Med 2003; 28:815-820

• FDG-PET is not disabled by metal susceptibility or metal beam hardening artefacts

• Multiple studies indicating good accuracy of FDG PET for detecting late local recurrence

PET in SarcomaApplications – Suspected Local Recurrence

Functional Imaging with PET in Sarcoma

Potential Applications

• Benign versus malignant

• Grading

• Biopsy guidance

• Staging

• Therapeutic monitoring

• Restaging ( local recurrence)

• Survival by PET response in 88 patients receiving radical radiotherapy

Mac Manus et al, J Clin Oncol 2003

FDG PET in Lung CancerTherapeutic Monitoring

0

20

40

60

80

100E

stim

ate

d p

erc

en

tag

e s

urv

ivin

g

0 6 12 18 24 30 36Months following PET scan

CRNo CR

(40)(48)

P = 0.0001

• Osteosarcoma of the left femur treatment with neoadjuvant chemotherapy

• Near complete metabolic response

PET in SarcomaApplications – Therapeutic Monitoring

p8455s0s1

Baseline Post-Chemo

Projection

Images

PET

Fused PET-CT

Clinical Trial Proposal

PET PET

Clinical Trial Proposal

PET PETPET PET

Study Design

-1

Screen SU11248 50mg po qd Break SU11248 50mg po qd Break

0 4 6 10 12Week 2 8

All Patients (30-40 planned): Response (RECIST) FDG PET

PK/PD 10 patients per group:

FLT PET Miso PET 15O-Water PET Biopsy

Two Types of Response

Week0

Week32

Week0

Week12

1-Shrinkage 2-Central Necrosis

Biologic & Anti-Tumor ActivityFDG PET FLT PET

Week 2

Week 12

Week 0

Pre- Treatment

Week 24

PET For Therapeutic MonitoringSerial FDG Imaging

• Metastatic malignant melanoma• Mixed metabolic response - CMR in right chest wall lesion• Had 10 days of drug, 6 day break and on drug at 50% dose

Baseline FDG PET

Week 2 FDG PET

SU-11248-pt-014

PET For Therapeutic MonitoringSerial FDG Imaging

• Metastatic malignant melanoma• Rapid clinical and FDG progression on reduced dose due to toxicity

Baseline FDG PET

Week 4 FDG PET

SU-11248-pt-014

Functional Imaging with PET in Sarcoma

Potential Applications - Conclusions

• Grading & Benign versus Malignant

provides useful complementary information

must be considered in context of clinical picture

chondroid matrix and sclerosing liposarcoma may produce false negative result

further studies required to determine if independently prognostic

• Biopsy guidance

very valuable, particularly PET/CT

Functional Imaging with PET in Sarcoma

Potential Applications - Conclusions

• Staging & re-staging

useful whole-body screen

NPV proportional to uptake in primary tumor

helpful in assessing possible local recurrence

• Therapeutic monitoring

potentially of enormous clinical value

changes evident rapidly (weeks)

further studies required to improve quantification of response

potential advantages for alternative tracers e.g. FLT