University of Pennsylvania Department of Orthopaedic Surgery

Joseph King, Eileen Crawford, Abass Alavi, Arthur Staddon, Lee Hartner, Richard Lackman

and Christian Ogilvie

PET Scan Markers for Survival in Patients with Soft Tissue Sarcomas

University of Pennsylvania Department of Orthopaedic Surgery

Background

• Soft tissue sarcomas (STS) are a heterogeneous group of malignant tumors

• Prognosis determined by CT, MRI, and biopsy • Problems/challenges:

– Local extent, metastasis, recurrence– Diagnosis, grading, monitoring treatment response

University of Pennsylvania Department of Orthopaedic Surgery

Background• FDG uptake proportional to growth rate of

neoplastic cells• PET SUVmax > 6 in sarcomas related to survival

and progression1

• PET has shown promise in predicting survival for lung and breast carcinomas2-4

• Poor PET response to chemotherapy in STS (< 40% decline in FDG uptake) associated with increased rate of recurrence and death5

1) Eary et al 20022) Kramer et al. 20063) Chen et al. 20044) Schwartz et al. 20055) Sheutz et al. 2005

University of Pennsylvania Department of Orthopaedic Surgery

Purpose

• Determine predictors of survival based on FDG-PET imaging for patients with soft tissue sarcomas– SUVmax– Response to chemotherapy– PET active lung nodules

University of Pennsylvania Department of Orthopaedic Surgery

Hypothesis

• Predictors for decreased survival will include:– High maximum standard uptake value (SUV)– FDG-enhancing lung nodules– Poor SUV-based response to chemotherapy

University of Pennsylvania Department of Orthopaedic Surgery

Materials and Methods

• Study Design: Retrospective review

• Study Group:– Treated with chemotherapy +/- resection

• High or intermediate grade sarcoma• Primary tumor > 5 cm, or metastatic disease

– PET scans done between 2003-2006– 1st PET done before all disease resected– Minimum follow-up 6 months– 14 patients with pre- and post-chemo PET scans

University of Pennsylvania Department of Orthopaedic Surgery

Materials and Methods

• Study Group:– 32 patients with STS– 14 excluded

• Bone sarcoma• Also had carcinoma• No gross disease at time of initial scan• Inadequate documented follow up

University of Pennsylvania Department of Orthopaedic Surgery

Materials and Methods

• Outcome Measures:1. Maximum SUV (primary sarcoma or metastasis)2. Number and location of PET detected metastatic lesions3. SUV-based response to chemotherapy

– Response: ≥ 40% decrease in SUV in over ½ of lesions– Stability: < 40% decrease in SUV in over ½ of lesions– Progression: SUV increase or new lesions

University of Pennsylvania Department of Orthopaedic Surgery

Patient Characteristics

Diagnosis NLeiomyosarcoma 10Synovial sarcoma 7Liposarcoma 4Malignant fibrous histiocytoma 4Sarcoma NOS 2Rhabdomyosarcoma 1Myxofibrosarcoma 1Atrial sarcoma 1Desmoplastic round cell tumor 1Extraosseous Ewing sarcoma 1

• Mean age = 47 (range 20-74) • 13 had mets on presentation• 15 developed mets during f/u

Location NLower extremity 11Pelvis 6Chest 5Abdomen 5Upper extremity 4Back 1

University of Pennsylvania Department of Orthopaedic Surgery

Results

• Mean follow-up = 49 months (range 7-172 months) • 10 alive at last f/u 6 with NED, 4 with metastatic disease• 5 patients had local recurrence after resection mean time to LR was 2.4 years

Prognostic factor N Mean Survival (months) P-value

SUVmax < 6 22 15.1 0.93

SUVmax ≥ 6 10 14.7

No nodules 19 21.6 0.007

1-3 nodules 9 10.7

No nodules 19 21.6 0.003

4+ nodules 4 6.2

1-3 nodules 9 10.7 0.20

4+ nodules 4 6.2

Progression 6 3.9 0.05

No progression 8 16.8

University of Pennsylvania Department of Orthopaedic Surgery

p=0.76

University of Pennsylvania Department of Orthopaedic Surgery

p=0.01p=0.01

University of Pennsylvania Department of Orthopaedic Surgery

p=0.001

University of Pennsylvania Department of Orthopaedic Surgery

Conclusions

• PET scan markers for decreased survival in patients with high grade STS include:– Presence of FDG-enchancing lung nodules– SUV-based disease progression during

chemotherapy

• SUVmax ≥ 6 was not a predictor for decreased survival

University of Pennsylvania Department of Orthopaedic Surgery

Discussion

• Obtaining pre- and post-treatment PET scans to evaluate treatment response of localized or metastatic STS provides useful prognostic information

• Maximum SUV was not found to have prognostic significance in this study– Lots of metastatic disease: selection bias with under

representation of patients with lower histologic grade and better prognosis?

University of Pennsylvania Department of Orthopaedic Surgery

Future directions

• Larger prospective studies of response to chemotherapy underway

• Data on histologic subtypes– Liposarcoma: Brenner et al. 2006– Rhabdomyosarcoma: Klem et al. 2007

• Probes other that glucose– Hypoxia– Apoptosis

University of Pennsylvania Department of Orthopaedic Surgery

Thank You!