PET/CT in NSCLC

Sofia N. Chatziioannou, MD Associate Professor

University of Athens Medical School Director of PET/CT Unit

Foundation of Biomedical Research of the Academy of Athens

When to use PET/CT in NSCLC

• Initial diagnosis (SPN)

• Initial Staging

• Restaging

• Radiation treatment planning

• Response to treatment

• Following neoadjuvant chemotherapy

• Prognostication

BOOP (bronchiolitis obliterans

organizing pneumonia)

SUVmax=5,3

71 year old

female, smoker

(45 pack years)

with increasing

mass on CT

ACCP Guidelines 2013

Solitary Pulmonary Nodule

• In the individual with a solid, indeterminate nodule that

measures > 8 mm in diameter and low to moderate pretest

probability of malignancy (5%-65%), we suggest that

functional imaging, preferably with PET, should be

performed to characterize the nodule (Grade 2C).

• Among patients with indeterminate nodules (by CT scan)

and high pretest probability, negative PET scan results do

not reliably exclude malignancy.

Chest. May 2013; 143(5 Suppl): e93S–e120S.

Variations in Uptake

• False Positive

– Inflammatory lesions (sarcoidosis, TB, rheumatoid nodules, etc)

– Benign neoplasia

• False negative

– <1cm

– Carcinoid

– lepidic-predominant adenocarcinomas (minimally invasive or in situ)

– mucinous adenocarcinomas

Benign nodule

PET vs. CT

Fletcher et al. JNM 2008;49:179-85

Part-solid nodules-ACCP

• In the individual with a part-solid nodule measuring > 8 mm in

diameter, we suggest repeat chest CT at 3 months followed by

further evaluation with PET, nonsurgical biopsy, and/or

surgical resection for nodules that persist (Grade 2C).

– Remark: PET should not be used to characterize part-solid lesions in

which the solid component measures ≤ 8 mm.

FDG uptake < mediastinal uptake

benign lesion

Minimally invasive adenocarcinoma

SUVmax=1.7

adenocarcinoma

Facts about NSCLC

• Even with clinical stage I, the 5-year survival rate after surgery is only 50%.

• Approximately 60% of cancer recurrences are presumably from extrathoracic micrometastatic involvement at presentation.

• PET/CT has gained significant recognition in the staging of non-small lung cancer.

Facts about NSCLC

• Patients with a strong clinical suspicion of stage I or II lung cancer (based on risk factors and radiological appearance) do not require a biopsy before surgery.

• Biopsy should be performed in the lesion that can lead to the highest stage.

• CT and PET before surgery should be within maximum 60 days before proceeding with surgical

evaluation. – Distant metastases may become evident on serial CT scans or PET

scans in 3% of untreated patients at 4 weeks and in 13% at 8 weeks (Mohammad N. Int J Radiat Oncol Biol Phys 2011;79 (2):446-472)

Vessell H, et al. J Thorac Oncol 2008;3:971-8

Outcome of pts with preoperative PET

188 randomly assigned

96 CWU

96 analyzed for primary

outcome

18 did not have

thoracotomy

92 CWU + PET

92 analyzed for primary

outcome

32 did not have

thoracotomy

Van Tinteren H et al. Lancet 2002; 359:13881392

PET reduced futile surgery by 51%, and prevented unnecessary surgery in 1 of 5

patients

Lung Cancer Staging

• PET/CT is more accurate than PET alone, CT alone or visually correlated PET & CT

CT PET vis CT&PET PET-CT

T status 31 (78%) 32 (80%) 31 (65%) 39 (98%)

M status 24 (64%) 32 (77%) 26 (70%) 31 (84%)

N status 8 (16%) 8 (16%)

Lardinois et al. N. Engl. J Med 2003;348:2500-7

PET/CT provided additional information in 20 of 49 patients (41%)

Facts about Lung Cancer NSCLC

• Patients with stage IA, IB, IIA and IIB disease can benefit from surgical resection.

• The current role of chemotherapy followed by surgery for selected patients with Stage IIIA disease remains controversial (van Meerbeeck JP, Kramer GW, Van Schil PE, et al. J Natl Cancer Inst 2007;99:442-450)

• Stages IIIB and IV disease almost never meet the criteria for surgery.

PET in Mediastinal Lymph Node Staging Name of Author # pts Prevalence (%) Accuracy (%) Sensitivity (%) Specificity (%) PPV (%) NPV (%)

Reed 2003 302 78 61 84 56 87 78

Saunders 1999 84 21 92 71 97 86 93

Vesselle 2002 118 21 92 71 97 86 93

Kahn 2004 157 - - 81 77 53 93

Poncelet 2000 62 15 82 67 85 43 94

Pieterman 2000 102 31 87 91 86 74 95

Gupta 1999 126 40 94 93 94 92 94

Bury 1996 50 58 84 83 86 89 78

Chin 1995 30 30 80 78 81 64 89

Stokkel 1999 187 - 96 90 97 85 98

Halter 2004 116 71 89 88 91 96 76

Oturai 2004 67 27 82 61 90 69 86

Nomori 2004 - - 98 78 98 74 98

Verlagen 2004 66 - - 58 90 83 71

Halpern 2005 36 - 69 50 77 45 80

Shim 2005 - - 84 85 84 - -

Pozo-Rodriguez 2005

132 28 77 81 76 56 91

PET-Mediastinal Lymph Node Evaluation

Ann Nucl Med;2015

DOI 10.1007/s12149-015-0958-6

Meta analysis: 18 studies

Ann Nucl Med;2015

DOI 10.1007/s12149-015-0958-6

Shortcomings:

False positives

False negatives

Non-standardization of what positive PET scan is.

PET-Mediastinal Lymph Node Evaluation

Hellwig D, et al. JNM 2007;1761-1766

Hellwig D, et al. JNM 2007;1761-1766

PET vs. CT-Mediastinal Lymph Node Evaluation

Gould MK et al. Ann Intern Med 2003;139:879-92

Gould MK et al. Ann Intern Med 2003;139:879-92

Right Lung Ca + Sarcoidosis

Mediastinal Lymph Nodes

• Tissue sampling is necessary for mediastinal lesions, regardless of the PET results, with possible exception of peripheral T1a lesions with negative CT and PET.

PET scan- Initial Staging Extrathoracic metastatic disease

• PET scan identifies extrathoracic disease in:

• Stage I: 7,5%

• Stage II: 18%

• Stage III: 24%

Reed CE et al. J Thorac Cardiovasc Surg 2003;44:1219-1224

Mac Manus et al. Int J Radiat Oncol Biol Phys 2001;50:287-93

Extrathoracic metastatic disease Facts

• PET scans can only detect macroscopic disease (>4mm).

• Positive results need either tissue or radiographic confirmation.

• However:

– Data are limited

– PPV is around 20%-30%

– NPV is not really known

Adrenal Metastatic Disease

Diameter>3cm Mean CT Attenuation > 10HU

SUVmax > 3.1 SUV Ratio > 1.0

Sensitivity (%) 40.5 100 97.3 97.3

Specificity (%) 96.6 60.3 75.9 65.5

PPV (%) 88.2 61.7 72.0 64.3

NPV (%) 71.8 100 97.8 97.4

Accuracy (%) 74.7 75.8 84.2 77.9

Brady, M. J. et al. Radiology 2009;250:523-530

Proposed systematic approach to the evaluation of adrenal nodules visualized at PET/CT

Brady, M. J. et al. Radiology 2009;250:523-530

Bone Metastatic Disease

Meta-analysis

Sensitivity Specificity

PET 91.9% 96.9%

MRI 80% 90.6

Bone Scan 91.8% 66.9%

Meta-analysis

Sensitivity Specificity

PET 92% 98%

MRI 77% 92

Bone Scan 86% 88%

Meta-analysis

Sensitivity Specificity

PET 93% 95%

Bone Scan 87% 82%

Clin Oncol 2010 Nov 2011;23:350-8

European Journal of Radiology 2012;81:1007– 1015

Acad Radiol 2012; 19:349–357

Brain Metastases

• In a study of 1,026 patients with multiple different cancers, unsuspected cerebral or skull metastases were detected in only 0,4% of the patients (Ludwig V, et al. Mol Imaging Biol 2002;4:359-362)

• MRI is the imaging procedure of choice

• PET is only useful to exclude other extrathoracic metastatic sites

Assessment of gross target volume (GTV)

Avoid radiation of normal tissues

Macapinlac H. Clinical applications of positron emission tomography/computed tomography treatment planning. Semin Nucl Med 2008;38:137-140.

James McElmurray The impact of 18F-FDG PET/CT imaging on radiation treatment planning for patients with non-small cell lung cancerJ Nucl Med. 2007; 48 (Supplement 2):400P

Post-obstructive pneumonitis vs. malignancy

Accurate delineation of the tumor

Better lymph node assessment

Radiation Therapy Planning

Mc Manus et al. Semin Nucl Med 2012;42:308-19

FDG-PET/CT GTV alteration

Radiation Treatment Planning

Radiation Treatment Planning

PET/CT

up to 4 weeks prior to RT

Initial Staging Following radiation therapy

Post-Radiation Changes

oPost-radiation changes may insist up to 2 years following radiation therapy

J Nucl Med 2009;50:31S-42S

PET-Response to Treatment

ΔSUVmax- Prognostic value

ΔSUVmax>50% between1st και 4th cycle

ΔSUVmax may indicate the patients who

would benefit from maintenance therapy

Yoon DH et al. Clin Cancer Res 2011;17:5093-100

Initial Staging Following chemoradiation

PET (+) following treatment is associated with worse prognosis AJR. 2000:174:769-74

Neoadjuvant therapy

PET should be used to exclude progression of disease or new

extrathoracic lesions

Mediastinal “down-staging” (low diagnostic accuracy) NCCN Guidelines 01.2016

Ann Thorac Surg.2004;77:254-9

Initial Staging Following Neoadjuvant

Therapy

Initial Staging

Following neoadjuvant chemotherapy

Disease Progression

18F-FDG PET/CT- Response to Treatment EGFR-TKI (gefitinib, erlotinib)

Van Gool MH et al. World J Radiol 2014;6:392-8

FDG PET/CT could identify the patients with EGFR mutation treated with ΤΚI will

respond to treatment.

18F-FDG PET/CT- response to treatment with EGFR-TKI (gefitinib, erlotinib)

Van Gool MH et al. World J Radiol 2014;6:392-8

oBetter prognosis (longer OS and PFS)

Initial Staging

Following Chemotherapy

Response to treatment

Metabolic Tumor Volume (MTV)

TLG (Total lesion glycolysis) = MTV X mean SUV

oMore accurate than SUV measurements

oIndependent prognostic factors

Im Hj et al. Eur J Nucl Med Mol Imaging 2015;42:241-251

JNM 2014;55:1062-68

Current guidelines do not propose FDG-PET for routine surveillance