role of functional imaging in sarcomas · koshkin vs, bolejack v, schwartz ln, et al. assessment of...

Role of Functional

Imaging in Sarcomas Dr Winnie Lam

Senior Consultant, Department of Nuclear Medicine & PET

Adj Assistant Professor, Radiological Sciences Academic Clinical Programme

5 November 2016

4th Singapore Sarcoma Symposium 2016

2

• Nuclear medicine is the medical specialty that

uses the tracer principle, most often with

radiopharmaceuticals, to evaluate molecular,

metabolic, physiologic and pathologic conditions

of the body for the purposes of diagnosis,

therapy and research.

2

What is Nuclear Medicine / Functional

Imaging?

3

■ PET for Sarcoma Detection & Grading

■ PET in Staging and Restaging Sarcomas

■ Sentinel Lymph Node Biopsy /

Lymphoscintigraphy in Sarcomas

■ PET in Correlation to Prognosis & Monitoring

Response

■ PET-guided Biopsy within a Suspected Sarcoma

3

4

■ Anatomical Imaging Modalities:

1. Radiographs (X-ray)

2. Computed Tomography (CT)

3. Magnetic Resonance (MR) ■ Primary diagnostic modalities

■ Exact location, size, local extent, bony destruction (biologic activity), intratumoral calcifications (phleboliths, amorphous calcification), proximity to neurovascular structures

■ CT chest for lung metastases

Imaging Techniques

4

5

■ Functional Imaging Modalities: 1. Bone scan (gamma camera)

• Incidence of bone metastasis is low

2. Lymphoscintigraphy / Sentinel Lymph Node Imaging (gamma camera / SPECT-CT)

3. Positron Emission Tomography (PET)

■ 18F-fluorodeoxyglucose (FDG) – glucose analog

■ Complementary information in diagnosis & treatment planning

Imaging Techniques

5

6

• Very sensitive (91%) & specific (85%) for detection

of high-grade sarcoma*

• Low positive predictive value (PPV) for nodal

metastases

• Standardized uptake value (SUV) – semi-quantitative

measure of radioactivity (FDG metabolic activity)

• Higher SUV correlated with histologic findings of

increased mitosis rate & cellularity (grade estimation) *Bastiaannet E, Groen H, Jager PL, et al. The value of

FDG-PET in the detection, grading and response to

therapy and soft tissue and bone sarcomas: a systematic

review and meta-analysis. Cancer Treat

Rev 2004;30(1):83–101.

PET for Sarcoma Detection & Grading

6

7

• Soft tissue / bone sarcoma metastasis

predominantly (75%) to the lung

• Mixoid / round cell liposarcomas -

retroperitoneum

• Synovial sarcoma / rhabdomyosarcoma / clear

cell sarcoma / epithelioid sarcoma - LN

• Many studies on FDG PET/CT in sarcomas

compared with conventional imaging (MR, CT,

bone scan, U/S, CXR) .

PET in Staging and Restaging Sarcomas

7

8

• Multicentre, 46 paediatric patients

• Ewing, osteo/rhabdomyosarcoma staging

• PET was superior in assessing LN involvement

& bone localizations • CT more accurate for pulmonary metastasis

Volker T, Denecke T, Steffen I, et al. Positron emission

tomography for staging of pediatric sarcoma

patients: results of a prospective multicenter trial.

J Clin Oncol 2007;25:5435–41..


8

9

• 19 paediatric patients

• Suspected sarcoma recurrence

• PET was useful for correct interpretation of

conventional imaging findings

• PET detected otherwise unknown metastasis in

2 patients Arush MW, Israel O, Postovsky S, et al. Positron

emission tomography/computed tomography with

18fluoro-deoxyglucose in the detection of local

recurrence and distant metastases of pediatric sarcoma.

Pediatr Blood Cancer 2007;49(7):901–5.


9

10

• Retrospective study, 89 patients

• High-grade bone & soft tissue sarcomas

• LN involvement – PPV 27%

• Distant metastasis – Sensitivity 95%

– Specificity 95%

– PPV 87%

– NPV 98% Fuglo HM, Jorgensen SM, Loft A, et al. The diagnostic

and prognostic value of 18F-FDG PET/CT in

the initial assessment of high-grade bone and soft

tissue sarcoma. A retrospective study of 89 patients.

Eur J Nucl Med Mol Imaging 2012;39(9):1416–24..


10

11


11

12

• Combined FDG-PET/CT is superior to either

modality alone

• PET/CT located 282 lesions in 20 patients

• CT alone identified 242 lesions

• PET alone identified 147 lesions

Antoch G, Kanja J, Bauer S, et al. Comparison of

PET, CT, and dual-modality PET/CT imaging for

monitoring of imatinib (STI571) therapy in patients

with gastrointestinal stromal tumors. J Nucl Med

2004;45(3):357–65.

PET/CT in Staging Gastrointestinal

Stromal Tumours (GIST)

12

13

• Commonly used in breast ca & malignant melanoma

• Radiopharmaceutical : Tc-99m Sulfur Colloid

• Dose 0.2mCi and volume 0.1ml

• Sentinel LN : LNs that first receive lymphatic drainage

from tumour

• Can have more than one sentinel lymph node

• Efficient tool to reduce postoperative long-term

morbidity (lymphoedema) without compromising local

control of disease

Sentinel Lymph Node Biopsy /


13

14



14

15



15

16

Lymphoscintigraphy plus SPECT-CT

16

17

• Prospective study, 28 patients • Rhabdomyosarcoma, epithelioid sarcoma, synovial sarcoma, soft

tissue Ewing’s sarcoma, fibrosarcoma, other soft tissue sarcomas • Median of 2.4 sentinel nodes / patient • SLNB identified tumour in 7/28 (25%), including 3 with normal

PET/CT • PET/CT demonstrated hypermetabolic LN in 14

– Sensitivity 57% – Specificity 52% – PPV 29% – NPV 79%

• SLNB can safely guide rational selection of LNs for biopsy • SLNB can identify therapy-changing nodal disease not

appreciated with PET/CT Wagner LM, Kremer N, Gelfand MJ,, et al. Detection of lymph node metastases in pediatric and adolescent/young adult sarcoma: Sentenel lymph node biopsy versus

fludeoxyglucose positron emission tomography imaging-A prospective trial. Cancer 2016 Aug 26. doi: 10.1002/cncr.30282. [Epub ahead of print]

SLNB plus SPECT-CT vs FDG PET in

Paediatric & Adolescent/Young Adult

Sarcoma

17

18

• Significant association between FDG uptake &

several pathologic markers:1

– Histopathological grade

– Tumour cellularity

– Proliferative activity (mitotic figure counts)

– Overexpression of p53

– Ki67 values in GIST2

1. Folpe AL, Lyles RH, Sprouse JT, et al. (F-18) fluorodeoxyglucose positron emission tomography as a predictor of pathologic grade and

other prognostic variables in bone and soft tissue sarcoma. Clin Cancer Res 2000;6:1279–87.

2. Kamiyama Y, Aihara R, Nakabayashi T, et al. 18F-fluorodeoxyglucose positron emission tomography: useful technique for predicting

malignant potential of gastrointestinal stromal tumors. World J Surg 2005;29(11):1429–35.

PET and Prediction of Prognosis

18

19

• 238 patients with FDG-PET before

chemotherapy / surgical resection

• PET result compared with OS & DFS

• SUVmax & FDG heterogeneous distribution

can distinguish between higher-risk patients &

lower-risk patients Eary JF, O’Sullivan F, O’Sullivan J, et al. Spatial heterogeneity

in sarcoma 18F-FDG uptake as a predictor of

patient outcome. J Nucl Med 2008;49(12):1973–9.

PET and Prediction of Prognosis

19

20

• Assessment of tumour response based on

changes in tumour size is not particularly helpful

in sarcomas.

Tabacchi E, Fanti S, Nanni C. The Possible Role of PET Imaging Toward Individualized Management of Bone and Soft Tissue Malignancies. PET Clin 2016; 285-296.

PET in Monitoring Response to Therapy

20

21

• PET allows detection of tumour regression /progression before morphologic alterations on CT & MR

• Metabolic response precedes volumetric decrease of tumours

• PET findings can aid in decision making about maintaining / modifying therapy

• Reduction in FDG uptake of >35% from pretherapy value predictive of histologically assessed treatment response

Benz MR, Czernin J, Allen-Auerbach MS, et al. FDGPET/

CT imaging predicts histopathologic treatment

responses after the initial cycle of neoadjuvant

chemotherapy in high-grade soft-tissue sarcomas.

Clin Cancer Res 2009;15(8):2856–63.


21

22

• Study of early response in GISTs • FDG-PET able to differentiate metabolic responders (11)

from metabolic nonresponders (4) after 1 week of imatinib treatment compared with clinical & radiologic response according to RECIST

• Mean SUVmax decreased in responders (65%), increased in nonresponders

• FDG-PET also correlated with clinical disease course (PFS)

• No significant difference in FDG uptake between scans 1 & 8 weeks after treatment initiation

• FDG response to imatinib is genuinely an early response

Jager PL, Gietema JA, van der Graaf WT. Imatinib mesylate for the treatment of gastrointestinal stromal tumours: best monitored with FDG PET. Nucl Med

Commun 2004;25(5):433–8.


22

23

• Case story of significant reduction in SUVmax (from

13 to 4) 24 hours after a single dose of imatinib (400

mg) Shinto A, Nair N, Dutt A, et al. Early response

assessment in gastrointestinal stromal tumors with

FDG PET scan 24 hours after a single dose of imatinib.

Clin Nucl Med 2008;33(7):486–7.

• Comparison with morphologic therapy assessment

• SUVmean decrease of 60% on day 8 of imatinib

• Partial response according to RECIST after 23

weeks Heinicke T, Wardelmann E, Sauerbruch T, et al. Very

early detection of response to imatinib mesylate

therapy of gastrointestinal stromal tumours using

18fluoro-deoxyglucose-positron emission tomography.

Anticancer Res 2005;25(6C):4591–4.


23

24

Donswijk ML, Hess S, Mulders T, et al. [18F]Fluorodeoxyglucose

PET/computed tomography in gastrointestinal malignancies. PET Clin

2014;9:435


24

25

• Progression / secondary resistance to imatinib as re-emergence of FDG uptake

• Suggest more complex interrelation with heterogeneous intratumoral & intertumoral clonal dedifferentiation:

• After cessation of imatinib, flares of FDG uptake observed in lesions that were metabolically inactive during therapy

• Some lesions may still be responsive to initial treatment, whereas some clones progress to resistance

• This may provide basis for combination therapy for different TKIs, like imatinib & sunitinib, instead of traditional complete switch in therapy

• Literature favours use of FDG-PET as primary method for treatment assessment in GISTs

Van den Abbeele AD. The lessons of GIST–PET and PET/CT: a new paradigm for imaging. Oncologist 2008;13(Suppl 2):8–13.


25

26

• Clinical trial of novel IGF1R antibody in Ewing

sarcoma

• PET was superior to anatomic imaging in

identification of response

• Early signal with FDG-PET on day 9 was the

best predictor of benefit (OS) Koshkin VS, Bolejack V, Schwartz LN, et al. Assessment of Imaging Modalities and Response Metrics in Ewing Sarcoma: Correlation with Survival.

J Clin Oncol 2016 Aug 29. pii: JCO681858. [Epub ahead of print]


26

27

• Source of misinterpretation: – Infectious/inflammatory diseases

– Postsurgical change

– Postradiotherapy inflammation .


27

28

• PET/CT-guided biopsy combines anatomic information from CT with PET metabolic characterization

• Large malignant lesions can be heterogeneous • FDG PET/CT to guide biopsy of highest metabolic

activity, reducing probability of tumour grade underestimation & consequential inappropriate approach

• PET-guided biopsy enables evaluation of lesions with exclusively FDG uptake without corresponding anatomic findings on CT

• When biopsy results are inconclusive / inconsistent with clinical & radiologic pictures, patient may benefit from PET-guided second biopsy

PET/CT in Biopsy

28

29

• Histology of biopsy site of 8 malignant lesions

(as suggested by FDG-PET) showed the most

pleiomorphism & highest mitotic index within the

sarcoma Hain SF, O’Doherty MJ, Bingham J, et al. Can FDG

PET be used to successfully direct preoperative

biopsy of soft tissue tumors? Nucl Med Commun

2003;24(11):1139–43.

PET/CT in Biopsy

29

30

• Benign skeletal lesions with intense FDG

uptake: – Osteochondromas

– Giant cell tumours

– Chondroblastomas

– Langerhans cell histiocytosis

– Desmoid tumours

– Fibrous dysplasia .

Pitfalls

30

31

1. FDG PET provides metabolic information about primary tumour (T)

but its main advantage is evaluation of LN involvement (N), distant

metastasis (M), and local relapse.

2. PET/CT does not provide anatomic details, so cannot be used to

evaluate local infiltration.

3. Sentinel Lymph Node Biopsy can guide rational selection of LNs

for biopsy in sarcoma patients & identify therapy-changing nodal

disease not appreciated with PET/CT.

4. SUVmax before therapy is prognostic & useful for therapy

assessment as compared with posttherapy SUVmax.

5. After radiotherapy, some false positives may occur because of RT-

related inflammation (reduces with time after RT).

6. PET has lower sensitivity than CT in detecting lung metastases (CT

can be acquired on PET/CT tomographs).

7. Some benign diseases especially in the bone can be

hypermetabolic (false positive).

What the Referring Clinician Needs to

Know

31

32 32

Department of Nuclear Medicine & PET

role of functional imaging in sarcomas · koshkin vs, bolejack v, schwartz ln, et al. assessment of...

Documents