PET-CT imaging for Thoracic Neoplasms

J. Sriprapaporn, M.D.

Siriraj Hospital

Mahidol University

Jiraporn_Onco PET/CT_LUNG_2016

Part 2: Clinical Indications for Oncologic PET/CT imaging

• PET/CT Reimbursement for F-18 FDG PET/CT in

Thailand

• PET/CT Imaging in LUNG DISEASES

Solitary pulmonary nodule (SPN)

Lung cancer-NSCLC***, SCLC

Mesothelioma



Oncologic Indications for 18F-FDG PET/CT Imaging

Differentiating benign from malignant lesions

Searching for an unknown primary tumor when metastatic

disease is discovered as the first manifestation of cancer or

when the patient presents with a paraneoplastic syndrome

Staging known malignancies

Monitoring the effect of therapy on known malignancies

Determining whether residual abnormalities detected on

physical examination or on other imaging studies after

treatment represent tumor or posttreatment fibrosis or

necrosis

Detecting tumor recurrence, especially in the presence of

elevated levels of tumor markers

Selecting the region for tumor biopsy

Guiding radiation therapy planning

Delbeke D et al. JNM 2006


PET/CT Guidelines in Radiotherapy Planning

http://www.bnms.org.uk/images/stories/guidelines/PET_in_Radiotherapy_Planning.pdf

2010


Weber WA et al. (2008) Technology Insight: advances in molecular imaging and an appraisal of PET/CT scanning

Nat Clin Pract Oncol doi:10.1038/ncponc1041

Figure 4 Impact of PET/CT on radiation treatment planning


PET-CT Reimbursement in Thailand [26-11-07]

From 1 JAN 2008, 40,000 Baht/test for only 2

Indications: Colon cancer & NSCLC

Colon cancer

1. KPS > 70

2. Suspected tumor recurrence due to rising CEA

3. Negative or unclear CT or MRI of abdomen to document recurrence

4. Abnormal CT or MRI supposed to be completely resected. (for curative aim)

5. If the first PET-CT scan as indicated is negative, the PET study can be repeated at duration not less than 3 mos.



Non-small cell lung cancer

1. KPS > 70

2. Staging for curative aim

2.1 Clinical stage T2-3, N1-2 and Mo

2.2 The patient had previous CT scan of chest adrenal and bone scan done.

Bone scan –ve for bone metastasis


Level of Evidence for Clinical Indications of F-18 FDG PET Scan

Level Meaning

A FDG PET is well established with lots of evidence support.

B FDG is useful but less literature support.

C FDG is potentially useful with minimal support.

D FDG has limited value and is NOT recommended.


Region Cancer Diagnosis Staging Rx ResponseRecurrence

or RestagingOverall

Brain Primary Brain Tumors C

Tumor vs Rad Necrosis B

Lymphoma vs Toxoplasmosis C

Head & Neck Head & Neck Cancers

Cervical Node Metas B B B A

Thyroid Cancer C B

Thoracic Solitary Pulmonary Nodule A

Pulm metas vs Benign pulm nodule C

NSCLC A B B

SCLC C

Mesothelioma C

Breast Breast Cancer B B B B

GI Gastric Cancer C

Esophageal Cancer D A B C

GI Stromal Tumors (GIST) * A

Colorectal Cancer C B C A

Lymphoma Lymphoma A A C

Skin Malignant Melanoma A A



or RestagingOverall

Heapatobiliary HCC C

Cholangiocarcinoma C

Pancreatic Cancer B B C B

Gynecological Uterine Cervical Cancer D B C C

Ovarian Cancer C C B

Endometrial Cancer C

Urological RCC C C C

Testicular Cancer C B

Bladder Cancer C

Prostate Cancer D

MSK MSK Tumors C

Soft tissue tumors C

OSM & Soft Tissue Sarcoma B

Ewing Sarcoma C

Hematologic Multiple Myeloma C


TNM Staging of NSCLC, 7th edition, 2009 [http://www.radiologyassistant.nl/en/p42459cff38f02/lung-cancer-new-tnm.html]

T1: Tumor WO invasion of lobar bronchus T2: Tumor > 3 cm but • Involves main bronchus > 2 cm distal to carina • Invades visceral pleura • Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung T3: Tumor > 7 cm or any of the following: • Directly invades any of the following: chest wall, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium, main

bronchus Atelectasis or obstructive pneumonitis of the entire lung • Separate tumor nodules in the same lobe T4: Tumor of any size that invades the mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, or with separate tumor nodules in a different ipsilateral lobe.



N Staging: Regional LN

N1: In ipsilateral perbronchial &/or ipsilateral hilar nodes & intrapulmonary nodes.

N2: In ipsilateral mediastinal &/or subcarinal nodes.

N3: Contralateral mediastinal, contralateral hilar, ipsi or contralat scalene or SPC nodes.

•Stage IIIA has a 5-yr survival of 10%.

•GREEN-resectable •RED-unresectable •Stage IIIA is possibly resectable, usually after combined-modality therapy

•Stage IIIB is virtually unresectable.


Comparison between 6th & 7th TNM staging editions

Jiraporn_Onco PET/CT_LUNG_2016 THORACIC NEOPLASM


THORACIC NEOPLASMS

Solitary pulmonary nodule (SPN), size < 3 cm.

DDx benign vs malignant- clinical indication = A

SUV > 2.5 malignant !

PET is best for nodule > 1 cm.

PET is better for nodule in upper lobe (less resp motion, less scatter from liver activity)

DDx pulmonary metastases vs benign nodule in a patient with known cancer. (C) Using SUV 2.5 or lesion/bcg ratio = 3.0, PET has 91% accuracy.

NSCLC

Staging (A)

Prognosis & therapy response (B)

Recurrence (B)

SCLC (C)

Mesothelioma (C) Jiraporn_Onco PET/CT_Lung_2015


F-18 FDG PET & Single Pulmonary Nodule (SPN)

DDx benign vs malignant

Clinical indication = A

SUV > 2.5 malignant !

PET is best for nodule > 1 cm.

PET is better for nodule in upper lobe (less resp motion, less scatter from liver activity)

False positive: active granulomatous/ inflammatory process, some benign tumors eg. leiomyoma.

False negative: Bronchioalveolar carcinoma (BAL), carcinoid, mucoepidermoid carcinoma, small lesions.


F-18 FDG PET & Single Pulmonary Nodule (SPN)

To identify pulm malignancy:

PET scan: sens 97%, spec 78% [metaanalysis by Gould MK 2001]

PET-CT: sens 97%, spec 85% [Kim SK 2007]

Contrast CT scan: sen 98%, spec 58%.

Negative PET scan highly likely benign.

Positive PET scan most likely malignant!.

Interpretation: SUVmax > 2.5 or hot > mediastinal blood pool.


Solitary Pulmonary Nodule

DxCT:

Primary tumor-Rt

Med node –ve

PET-CT (12-06):

Hypermetabolic, SUVmax = 8

Med node –ve

Distant met-No


Lung

Cancer


Cancer Statistics 2015 Siegel RL 2015

1. Prostate 2. Lung 3. Colon

1. Breast 2. Lung 3. Colon

Lung


Lung Cancer: Background

Worldwide, bronchogenic carcinoma is the most common cause of cancer death in both men and women.

In the US, approximately 1/3 of cancer deaths occur as a consequence of lung cancer, and approximately 170,000 new cases of lung cancer occur annually.

The 5-year survival rate is 14%, and it has largely remained unchanged for decades.

Lung cancer kills more people than colorectal, breast, and prostate cancers combined.

http://emedicine.medscape.com/article/358433-overview Last updated on Nov 7, 2013

http://emedicine.medscape.com/article/358433-overview





Lung Cancer in USA

Lung CA 13% of all new CA cases

Lung CA is the leading cause of cancer-related deaths.

28% of all cancer deaths

60% dies within 1 year

75% dies within 2 years

5-yr survival (in all stages) 15% since most

cases are advanced at presentation.

Surgical resection of solitary lung CA 5-yr survival

40-80%

www.cancer.org


Lung cancer: Histology

SCLC: minority (14%), usually poor diff, rapid growing,

Rx by CMT+ERT

NSCLC: 85% including adenocarcinoma

(bronchoalveolar*), squamous, large cell, carcinoid, etc.

Rx: stage IA, IB Surgery alone

Upto IIIA Surgery + CMR

IIIB, IV CMT/ERT for palliation

Coleman E

* Can produce false negative FDG PET

(SCC higher FDG avid > adenoCA)


NSCLC Staging

Staging & mode of Rx

After the initial Dx of NSCLC,

accurate staging is crucial for

choosing an appropriate Rx

modality.

Staging & prognosis

Stage I 5-yr survival 50%

Stage II 30%

Bruzzi J 2006


Roles of PET/CT in NSCLC

Staging [A]: T N M

Treatment response [B]

Recurrence or restaging

(after complete Rx) [B]


PET for NSCLC Staging


PET can prevent unnecessary surgery in 1/5 pts.

PET is valuable in both mediastinal and distant staging.

Mediastinal staging: PET is most useful !

Distant staging: PET is most useful in clinical stage III, IV.

PET has limited role in clinical stage I tumors due to low med. & distant metas.

PET detects unsuspected distant metas. in about 10%.

PET/CT is suitable for assessing chest wall and mediastinal invasion.


T-Staging of NSCLC

T staging: Diagnostic CT scan*

PET assess metabolic activity, which reflects cell turnover rate & may indicate tumor aggressiveness.

SUV of primary tumors has prognostic value

SUV inversely correlates with the lesions’ doubling time.

SUV < 10 median survival 24 Mo

> 10 11 Mo

SUV > 10 & size > 3 cm 6 Mo

PET helps predict likelihood of tumor recurrence & thus guides for additional adjuvant CMT or ERT.

PET is more precise to detect chest wall invasion.


NSCLC w chest wall invasion?

PET or CT alone is difficult to determine early invasion of the chest wall but the combined image reveals that abnormal metabolic activity within the tumour does not reach the

pleural surface.

Wechalekar K 2005

Figure 5.

Fused PET/CT

CT

PET


NSCLC w asso. peripheral collapse and consolidation

The exact extent of the tumour was difficult to ascertain on CT or PET alone but on the combined image the differentiation can be clearly appreciated.

Wechalekar K 2005

Figure 6.


N-Staging of NSCLC

CT or MRI discriminate benign vs malignant nodes

based on size:

PET not base on size has higher diagnostic accuracy.

Meta-analysis 1999 [R27] : PET vs CT sen/spec:

79/91% vs 60/77%

Combine PET/CT : 89/94%

FN (8%) & FP do exist!

FDG PET/CT for mediastinal node staging.


Regional Lymph Node Classification System

Supraclavicular zone (1)

1. Low cervical, supraclavicular and sternal notch nodes

Superior Mediastinal Nodes (2-4)

2. Upper Paratracheal: above the aortic arch, but below the clavicles.

3A. Pre-vascular: these nodes are not adjacent to the trachea like the nodes in station 2, but they are either anterior to the vessels.

3P. Pre-vertebral: these nodes are not adjacent to the trachea like the nodes in station 2, but they are behind the esophagus, which is prevertebral (3P).

4. Lower Paratracheal (including Azygos Nodes): below upper margin of aortic arch down to level of main bronchus.

Aortic Nodes (5-6)

5. Subaortic (A-P window): nodes lateral to ligamentum arteriosum. These nodes are not located between the aorta and the pulmonary trunk, but lateral to these vessels.

6. Para-aortic (ascending aorta or phrenic): nodes lying anterior and lateral to the ascending aorta and the aortic arch.

Inferior Mediastinal Nodes (7-9)

7. Subcarinal.

8. Paraesophageal (below carina).

9. Pulmonary Ligament: nodes lying within the pulmonary ligaments.

Hilar, Interlobar, Lobar, Segmental and Subsegmental Nodes (10-14)

10-14. N1-nodes: these are located outside of the mediastinum. They are all N1-nodes.

Lymph node staging is done according to the American Thoracic Society mapping scheme.



N Staging: Regional LN

N1: In ipsilateral perbronchial &/or ipsilateral hilar nodes & intrapulmonary nodes.

N2: In ipsilateral mediastinal &/or subcarinal nodes.

N3: Contralateral mediastinal, contralateral hilar, ipsi or contralat scalene or SPC nodes.

•Stage IIIA has a 5-yr survival of 10%.

•GREEN-resectable •RED-unresectable •Stage IIIA is possibly resectable, usually after combined-modality therapy

•Stage IIIB is virtually unresectable.


PET for N-Staging of NSCLC

CT: Left NSCLC w a pathologic AP window node (N2) (A white), and a non-pathologic retrocaval-pretracheal contralateral mediastinal node (N3) (B yellow).

PET-FDG images: increased tracer accumulation within both nodes, consistent with metastases.

Thus, PET is more sensitive than CT in detect small hypermetabolic LN metastasis.

A A

B B B


Current Concepts in the Mediastinal Lymph Node Staging of NSCLC

Henk Kramer, MD and Harry J.M. Groen, MD, PhD

Ann Surg. 2003 August; 238(2): 180–188.

In conclusion, PET is very accurate in the mediastinal lymph node staging of NSCLC, and more accurate than CT.

With the high NPV, a negative mediastinum on PET leads directly to thoracotomy without further preoperative mediastinal staging.

[False negative rate in mediastinum : 5-8% VS mediastinoscopy 9%-R16]

The lower PPV makes cytologic or histologic confirmation necessary in case of a positive mediastinum on PET.[13]

[False positive rate in mediastinum: 13-22% R16.Detterbeck FC 2004]

The detection of unexpected distant metastasis in about 15% of the cases is another important advantage of PET.[13]


M-Staging of NSCLC

Likelihood of distant metas. increases with higher T

stage [adeno CA.]

The most common metas. sites are adrenal gland

(upto 20% at initial staging), brain, bone, liver.

PET detect clinically unsuspected distant metas. in

upto 28% of Pts. & alter Rx as 53%.


PET & Adrenal Gland Metastasis

Adrenal gland with increased FDG uptake > liver activity is highly sen & spec with accuracy of > 92%.

FP in benign adenomas

FN: is very small lesion or hemorrhage, necrosis

Integrated PET/CT is helpful.

Jiraporn_Onco PET/CT_LUNG_2016 Figure 6: (a) Coronal PET MIP and transverse (b) contrast-enhanced CT

and (c, d) PET/CT

NSCLC w Lt central tumor (a,b,c)

Lt med LN met (a)

Primary CA w asso. distal atelectasis (b,c)

Infiltration of tumor into left pulmonary artery (b,c)

Rt adrenal gl met (a,d)

Retroperitoneal node met (a)

D

ADR

ADR

RP LN

Med LN

Von Schulthess 2006

A B C


Other Distant Metastatic Sites

Brain Met: upto 18%-PET not quite good MR-CT

Liver Met: similar

Bone Met: PET sen is probably > bone scan esp BM

involvement, but FP in DJD, physiologic marrow activity.

Unsexpected bony lesions may require further Ix.

Pleural Met: PET Sen 92-100%, spec 67-71%, NPV

100%, PPV 63-79%.


Summary: Impact of PET on staging and management of NSCLC

Noninvasive lung cancer staging was improved substantially by the use of PET/CT.

PET/CT can stage both intra- and extrathoracic sites in one examination, with a better accuracy than conventional imaging.

For preoperative mediastinal LN staging, PET has become the most accurate noninvasive diagnostic test.

PET in preRx staging led to a stage shift in about half (range, 19%–62%) of patients staged with CT scan. Mostly = upstaging (range, 12%–56%), mainly related to

the detection of unexpected distant metas by PET (range, 10%–36%)

Less frequently = downstaging In 19% to 46% of cases, PET imaging change of

treatment plan.

Wynants J et al. RCNA 07


Prognosis and Therapy Response

1. Prognosis: The amount of tumor uptake & tumor stage are predictors of survival.

2. Early prediction: early change in FDG uptake during CMT or ERT may predict response.

3. Late prediction: PET has potential role in restaging & response prediction after induction therapy.

4. Radiotherapy planning: * postobstructive atelectasis

B


FDG PET for Monitoring CMT Response

Intense tumor uptake and nodal uptake of F-18 FDG

Reduced metabolic activity Respond to treatment


Limitations of PET after Rx

Primary tumor: PET is sensitive but not specific for

detection of residual disease in primary tumor.

Mediastinal nodes: PET is specific but limited

sensitivity for restaging med. LN.

Hilar nodes: PET is more accurate than CT in

detecting residual tumor, except in N1 disease where

PET & CT are comparable.


RECURRENCE OF NSCLC

PET is accurate > CT alone.

PET can DDx local tumor recurrence vs postRx change,

sen 97-100%, spec 62-100%. (specificity is limited due

to presence of inflammatory reaction following Rx)

PET/CT increases specificity.

SUV has prognostic value.

B



or RestagingOverall

Brain Primary Brain Tumors C

Tumor vs Rad Necrosis B

Lymphoma vs Toxoplasmosis C

Head & Neck Head & Neck Cancers

Cervical Node Metas B B B A

Thyroid Cancer C B

Thoracic Solitary Pulmonary Nodule A

Pulm metas vs Benign pulm nodule C

NSCLC A B B

SCLC C

Mesothelioma C

Breast Breast Cancer B B B B

GI Gastric Cancer C

Esophageal Cancer D A B C

GI Stromal Tumors (GIST) * A

Colorectal Cancer C B C A

Lymphoma Lymphoma A A C

Skin Malignant Melanoma A A

SUV cutoff 2.5


NSCLC Staging


PET can prevent unnecessary surgery in 1/5 pts.

PET is valuable in both mediastinal and distant staging.

Mediastinal staging: PET is most useful !

Distant staging: PET is most useful in clinical stage III, IV.

PET has limited role in clinical stage I tumors due to low med. & distant metas.

PET detects unsuspected distant metas. in about 10%.

PET/CT is suitable for assessing chest wall and mediastinal invasion.



Non-small cell lung cancer

1. KPS > 70

2. Staging for curative aim

2.1 Clinical stage T2-3, N1-2 and Mo

2.2 The patient had previous CT scan

of chest adrenal and bone scan done.


Limitations of PET

False negative:

Bronchoalveolar carcinoma,

Carcinoid,

Mucoepidermoid carcinoma,

Small lesions.

False positive:

Infection,

Inflammation,

Granulomatous disease.

Von Schulthess 2006


Suggested Reading

Sahiner I, Vural GU. Positron emission tomography/computerized tomography in lung cancer. Quant Imaging Med Surg. 2014 Jun;4(3):195-206. Review. PubMed PMID: 24914421; PubMed Central PMCID: PMC4032918.

Padma S, Sundaram PS, George S. Role of positron emission tomography computed tomography in carcinoma lung evaluation. J Cancer Res Ther. 2011 Apr-Jun;7(2):128-34. Review. PubMed PMID: 21768697.

Truong MT, Viswanathan C, Erasmus JJ. Positron emission tomography/computed tomography in lung cancer staging, prognosis, and assessment of therapeutic response. J Thorac Imaging. 2011 May;26(2):132-46. Review. PubMed PMID: 21508735.[ovid]


Suggested Reading

Baum RP, Swietaszczyk C, Prasad V. FDG-PET/CT in lung cancer: an update. Front Radiat Ther Oncol. 2010;42:15-45. Epub 2009 Nov 24. Review. PubMed PMID: 19955789. [http://www.karger.com/Article/FullText/262458]

Erasmus JJ, Macapinlac HA, Swisher SG. Positron emission tomography imaging in nonsmall-cell lung cancer. Cancer. 2007 Nov 15;110(10):2155-68. PubMed PMID:17896784.

Nickell LT Jr, Lichtenberger JP 3rd, Khorashadi L, Abbott GF, Carter BW. Multimodality imaging for haracterization, classification, and staging of malignant pleural mesothelioma. Radiographics. 2014 Oct;34(6):1692-706. doi:10.1148/rg.346130089. PubMed PMID: 25310424.

Health & Medicine

PET-CT imaging for Thoracic Neoplasms