Imaging with Positron Emission Tomography/ Computed Tomography ( PET/CT)
PET-CT in Lung Cancer: Positron emission tomography – computed tomography to whom, when ?
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Transcript of PET-CT in Lung Cancer: Positron emission tomography – computed tomography to whom, when ?
PET-CT in Lung Cancer:Positron emission tomography – computed tomography
to whom, when ?
Jann Mortensen, MD, DMSci
Department of Clinical Physiology, Nuclear Medicine & PET,
Rigshospitalet University Hospital of Copenhagen,Denmark
[email protected], 26 april 2008
Fused PET + CTCT PET
Anato-metabolic imaging2
PET - CT
Investigates functional changes in the body tissues and anatomy
simultaneusly
FDG signal in tumor is dependent on 1) delivery (blood flow),2) transport into the cells (glut), and 3) phosporylation (hexokinase)
Physiology of FDG tumor uptake
FDG tumor uptake ~ number of viable cancer cells
R.Wahl. Priciples and practice of positron emission tomography, 2002
BrainSalivary glands
LarynxThyroidHeart
GI tract incl liverGenito-urinary tract
Bone marrowLymphoid tissue
Brown fat
Physiological uptake of FDG
Main indications for PET in lung cancer
• Characterising pulmonary nodules which are borderline for malignancy on CT
• And cannot be easily biopsied
• Staging in NSCLC– Preoperative evaluation
• N and M (nodes and metastasis)
55 studies with > 2000 patients with histologic or long-term follow-up
Fischer BM, Mortensen J, et al.
Lancet Oncol 2001;2:659-66
Publications of PET & PET/CT in Lung cancer
PETPETCT
NSCLC
SCLC
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PubMed April 2008
– Indeterminate single pulmonary nodule/mass on CT
• Malignant or benign ?
– N=16 studies
– Sensitivity 0.96 (0,90-1,00)
– Specificity 0.78 (0,69-0.95)
• Size: 1-4 cm• 1474 nodules (JAMA 2001; 285: 914-24)• Only few nodules <1 cm:
FDG-PET in solitary pulmonary nodules
FDG-PET can discriminate between malignant / benign ≥ 10 mm solid pulmonary nodules !!!
•FDG-PET has a high negative predictive value, can correctly exclude malignancy in the vast majority of nodules seen in daily practice. • ~ changes management in > 26 % of patients
•A surgical procedure can be avoided, and a repeat CT after 3 (6, 12 and 24) months can be used to confirm the absence of growth.Lancet Oncol 2001; 2: 659-66 Lung Cancer 2004; 45: 29-30.
FDG PET in >1 cm nodules
What is the diagnostic value in < 1 cm small nodules ?
9 mm nodule found on high-resolution CT
18F-FDG PET
57 yr male with COPD
transaxial coronal saggital
attenuation corrected RH - PET / jm (ap)
Diagnosis and staging(PET suggests T1 N0 M0)
57 yr male with COPD
Fischer BM, Mortensen J, et. al. Nucl Med Commun 2004; 25: 3-9.
On going screening study in Copenhagen: • Included 4000• Yearly CT vs. Control in 5 yrs• now 3 year
Value of PET in characterising indeterminate SPN 6-15 mm detected with low-dose CT
- all SPNs followed-up with re-CT at 3 months to assess growth
PET in ”The Danish randomisedlow-dose CT screening study of lung cancer”
Initial 9x12x9 mm solid nodule in R3, PET positive + 2 N2
PETpos + CT growth -> Biopsi/Mediastinoscopy: T1N2M0 (->Chemotherapy)
PET positive case
PET in Danish randomised low dose CT screeningPET in Danish randomised low dose CT screening
CT + PET axial
10 mm solid nodule in L3 PET negative CT stationary
a PET negative case
PET in Danish randomised low dose CT screeningPET in Danish randomised low dose CT screening
Jann Mortensen, klinisk fysiologi, nuklearmedicin og PET, Rigshospitalet
20
PET data from CT- screening in Milano
With PET : complete diagnostic workup < 4 months at baseline and < 2 months at 2-5 yrs
PET in 68 SPN >7 mm ~ 1,4% of 1.035 participants
Danish study:Accurracy.
89%
FDG PET in small nodules (<10 mm)
• PET is promising as a tool in lung cancer screening with low-dose CT
[Lung Cancer 2004; 45:19—27] [Nucl Med Commun 2004; 25: 3-9]
[Am J Respir Crit Care Med 2005; 171:1378-83][Lancet 2003;362:593-79]
• The interpretation of FDG-PET findings in subcentimetric nodules is at present unsolved
• [Vansteenkiste JF. Lung Cancer 2004; 45: 29-30].
Staging T N M status (in one exam)
•Conventional staging is inaccurate [Lancet 1996;347:649–653].
Oturai, Mortensen, Eigtved et al. J Nucl Med 2004;45:1351-7
Preoperative staging with FDG-PET
PET for staging:•Staging the MediastinumPET more accurate than CT for detection of locoregional metastases PET sensitivity >84%, specificity >89% (18 prospective studies)
• Detecting distant metastases:PET sensitivity >90%, specificity >90%and better than CT (17 prospective studies)
•Change in management• >25% of patients (15 prospective studies)
Pieterman et al. N Engl J Med 2000;343:254-61
102 patients with resectable NSCLC, 6 months follow-up,
histopathological reference. (N) metastasis Sensitivity Specificity PET 91 % 86 %CT 75 % 66 %
(M) metastasis: PET identified distant metastases not foundby standard methods in 11 of 102 patients:
PET identified a different stage in 62 patients:stage was lowered in 20 and raised in 42
Prospective study of Preoperative staging with PET vs. standard staging (CT, ultrasound, bone scanning/ biopsy)
Randomised study of PET staging
• Effect parameter: no. unneccesary thoracotomy´s• 188 ptt. usual work-up +/- PET, 1 yr follow-up• 9 Deutch hospitals (1 dedicated PET center)
• PET reduced the no. unneccesary thoracotomy´s:– PET 32 (41%) , + PET 18 ptt (21%)
• For each 5 PET scans one unneccesary thoracotomy was avoided– reduced cost per patient with PET: > 1.000 EURO
(PLUS study. Lancet 2002; 359: 1388-92)
Mediastinoscopy, EUS, EBUS and PET/CT
Mediastinal staging with CT, PET, and endoscopic esophageal ultrasound (EUS)
EUS+FNA better ? for locoregional staging (N)• PET was superior (higher sensitivity and specificity), to CT but also to EUS.PET was superior (higher sensitivity and specificity), to CT but also to EUS.
•[Chest 2003;123(suppl 1):137S–146S]. [Chest 2003;123(suppl 1):137S–146S].
• PET and EUS with fine-needle aspiration had similar sensitivities (79%) for advanced cancer, but PET and EUS with fine-needle aspiration had similar sensitivities (79%) for advanced cancer, but EUS with FNA had a superior specificity (100% vs. 72%).EUS with FNA had a superior specificity (100% vs. 72%).
• [Am J Respir Crit Care Med 2003;168:1293–1297][Am J Respir Crit Care Med 2003;168:1293–1297]
• EUS with fine-needle aspiration had higher sensitivity (87% vs. 61%), specificity (100% vs. 91) and EUS with fine-needle aspiration had higher sensitivity (87% vs. 61%), specificity (100% vs. 91) and accuracy (94% vs. 77%) than PET. accuracy (94% vs. 77%) than PET.
•[Clin Gastroenterol Hepatol 2006;4:846-51].[Clin Gastroenterol Hepatol 2006;4:846-51].
• In 5 papers on > 300 patients with PET positive N (N1-3): EUS+FNA had high accuracy and in ~50% detected malignancy obviating the need for further surgical procedures •[Chest 2005;128:3004-9 & 2005;127:130-7][Ann Thorac Surg 2005;80:1231-40][Thorax 2004;59:596-601][Lung Cancer 2004;44:59-60].
Mediastinal staging with CT, PET, and endobronchial ultrasound (EBUS) with TBNA
• 102 patients with potentially operable suspected lung cancer.
Gold standard: histology-cytology [Chest 2006;130:710-718].
EBUS with TBNA vs. PET vs. CT:
• Sensitivity (92% vs. 80% vs. 77%),
• Specificity (100% vs. 70% vs. 55%),
• Accuracy (98% vs. 73% vs. 61%).
EBUS + TBNA better ? for locoregional staging (N)
In the majority of 33 patients with PET positive N (N1-3): EBUS-TBNA could detect malignancy obviating the need for futher surgical procedures [Eur Respir J 2006;27:276-281].
Publications of PET & PET/CT in Lung cancer
PETPETCT
NSCLC
SCLC
0
50
100
150
200
250
300
350
400
Ref
eren
ces
PubMed April 2008
”PET/CT improves staging in 20-40% of lung cancer patients compared to PET and CT” (T and N status)
Lardinois D et al. N Engl J Med 2003;348:2500-7
PET/CT improves staging in lung cancer
“Compared to PET, PET/CT better predicts stage I and II, as well as T and N status”Cerfolio RJ et al. Ann Thorac Surg 2004; 78: 1017–23
”PET/CT is significantly better than CT in NSCLC staging and provides enhanced accuracy and specificity in nodal staging” (10 FN Nodes with CT and 5 with PET/CT)
Shim SS et al. Radiology 2005; 236:1011-9
”PET-CT is more accurate, sensitive and specific compared to CT alone in nodal staging. Nael Al-Sarraf et al. Lung Cancer 2008;60:62-8
PET/CT 10-15% more accurate than PET
Extrathoracic metastasis• 40% with NSCLC have distant metastases at presentation, most often in the
adrenal glands, bones, liver, or brain [Ann Thorac Surg 1996;62:246–250].
• Adrenal glands: 10% of NSCLC have enlarged adrenal glands on CT, 2/3 being benign.
PET has high sensitivity (100%) and specificity (80%–100%) -> reduces number of unnecessary adrenal biopsies.
• Bone: Bone scintigraphy good sensitivity (90%), low specificity (±60%), PET similar or higher sensitivity (90%), similar or higher specificity ( 98%), and higher accuracy (96%).
• Liver: US and/or CT and /or MR remain the standard imaging techniques for the liver. No good comparisons studies. Additional diagnostic information by PET combined with CT, in the differentiation of hepatic lesions that are indeterminate on conventional imaging.
• Brain: FDG-PET low sensitivity (60%) not suited for the detection of brain metastases.
The Oncologist 2004; 9 (6): 633-43; (Lung Cancer 2004;44,317-25)
True positive FDG-PET in spine, false negative bone scan at presentation, but true positive 3 months later
Lung Cancer (2004) 44, 317—325
Adrenal lesion
Diagnostic value of PET in lung cancer
• Sensitivity ~ 97 % (SPN); ~ 73% (N staging)
• Specificity ~ 78 % (SPN), ~ 93% (N staging)
• Reasons for false negative ?
• Reasons for false positive ?
Solitary pulmonary nodules (SPN) Mediastinal staging (N)
Value of PET in lung cancer
• Reasons for false negative– Small size (resolution 4-6 mm,
respiratory movement)
– Well-differentiated tumors: • Some bronchioalveolar carcinoma (GGO)• Some carcinoids (Neuroendocrine tumors)• E.g. Adenocarcinoma• E.g. Renal cell carcinoma
False positive• Inflammation
– Granulomas: – Tuberculosis– Sarcoidosis– Histoplasmosis– Silicosis– BOOP, etc.
• Iatrogenic causes– Invasive procedures– Talc pleurodesis– Radiation sequelae
• Focal physiological FDG uptake– Gastrointestinal tract– Striated muscles– Brown fat– Artheroschlerotic plaques
Pitfalls of FDG-PET in lung cancer
TB in a 58-year-old man. (A) chest radiograph shows two nodules (b) coronal FDG PET scan shows increased uptake (solid arrow) in the left upper lobe nodules (SUV 4). Radiology 2000 6:117-21
Fischer BM, Mortensen J.
Respiration 2006;73:267-76
Sarcoidosis
Milman N, Mortensen J, Sloth C. Respiration. 2003;70:408-13.
Before treatment:
After inhaled steroid:
After prednisolone:
Localisation of activity in- and outside lungs:
Monitoring:
Indication for use of PET
Guidelines
• PET/CT is now implemented in guidelines
PET & PET/CT in guidelines for staging lung cancer to improve staging (Nodes+Metastases) & avoid unneccesary surgery
ESTS guidelines for preoperative lymph node staging in NSCLCEur J Cardio-thoracic Surgery 2007; 32:1-8
Noninvasive Staging of Non-small Cell Lung Cancer*
ACCP Evidenced-Based Clinical Practice Guidelines (2nd Edition) Silvestri, G. A. et al. Chest 2007;132:178S-201S
The Danish National Board of Health, 18 jan 2008:PET/CT in lung cancer staging for potentially curable patients
STAGING OF NSCLC
Invasive procedures can be omitted in patients with peripheral tumors and negative mediastinal PET (N0)
In case of central tumors, PET hilar N1 disease, low SUV of primary tumor and LNs 16mm on CT, invasive staging remains indicated.
ESTS-guidelines
PET positive mediastinal findings should always be confirmed cyto-histologically. so staging remains indicated.
De Leyn et al. Eur J Card-Thor Sur 2007;32:1-8
Newer indications for PET in lung cancer
• Prognostic information from SUV
• Evaluation of treatment effect ->
• PET/CT for planning of radiation field
• Staging and monitoring SCLC ->
• Staging Mesothelioma
PET predicts survival
SUV median survival < 10 2 yr > 10 1 yr + mass >3 cm ½ yr
• Ahuja et al. Cancer 1998; 83 ; 918-24
In multivariate analysis, the SUV was independently predictive of disease-free and overall survival
• Vansteenkiste J, Fischer BM, Dooms C, Mortensen J. Lancet Oncol 2004; 5: 531–40
Newer indications for PET in lung cancer
• Prognostic information from SUV
• Evaluation of treatment effect ->
• PET/CT for planning of radiation field
• Staging and monitoring SCLC ->
• Staging Mesothelioma
1. Re-staging after neoadjuvant therapy (invasive best)
2. Early assessment (Reduction in metabolism correletes closely to outcome)
3. Re-staging after completion of therapy (scar/residual tumor)
Vansteenkiste J, Fischer BM, Dooms C, Mortensen J. Lancet Oncol 2004;5:531-40
Newer indications for PET in lung cancer
• Prognostic information from SUV
• Evaluation of treatment effect ->
• PET/CT for planning of radiation field
• Staging and monitoring SCLC ->
• Staging Mesothelioma
PET/CT guided RT improves radiation dose to the tumorand metastases and reduce dose to adjacent normal tissueTarget volumes in NSCLC were changed by PET/CT:• Several studies show changes between 35-62 % (Increased and decreased)• No studies with patient outcome yet
Newer indications for PET in lung cancer
• Prognostic information from SUV
• Evaluation of treatment effect ->
• PET/CT for planning of radiation field
• Staging (and monitoring) SCLC
CT/Bone scint/bone marrow PET PET/CT Sensitivity 79% 93% 93%Specificity 100% 83% 100%PET/CT (n=32) changed stage in 17% of SCLC (LD->ED in 10%) “PET/CT can simplify and perhaps even improve the accuracy of the current staging procedure”. Fischer MBB, Mortensen J et al. Ann Oncol 2007;18(2):338-45
Brink et al (PET only, n=120) Significantly superior to CT in the detection of distant metastases: PET changed stage in 12% (upstaging 10, downstaging 3 of 120)
Newer indications for PET in lung cancer
• Prognostic information from SUV
• Evaluation of treatment effect ->
• PET/CT for planning of radiation field
• Staging and monitoring SCLC ->
• Staging Mesothelioma
PET/CT for:• Extent of tumour and invasion?• Preop. staging extrathoracic/contralat. metastasis (not N1,2)• Monitoring treatment• Prognosis (high metabolism -> bad prognosis)
J Nucl Med. 1999 Aug;40(8):1241-5.
Semin Oncol. 2002 Feb;29(1):26-35
Lung cancer 2005;49:s27-s32
J Thoracic Cardiovasl Surg 2005;129:1364-1370
Conclusion• Diagnosis of SPN
– Differentiate between benign/malignant SPN, unable to be biopsied• High negative predictive value
– the uptake (metabolism) is an independent prognostic factor (high->bad prognosis)– PET of value as adjunct to low-dose CT lung cancer screening
• Staging PET/CT improves conventional staging (CT+US+bone scintigraphy)
– PET/CT changes stage and treatment in 10-50 % of patients• Usually a higher stage is found• Avoids unneccesary thoracotomy (in 10-20%) due to N2-3 or M disease- Mediastinoscopy may be avoided if PET/CT is normal in the Mediastinum (non-central T), but
needs to be performed if PET/CT is positive
- Emerging indications:- restaging- treatment monitoring,- radiation field planning,- staging SCLC and Mesothelioma
Perspectives for PET/CT in lung cancer
• Simplify the staging procedure• one-stop procedure
– More often assign the correct stage• And correct treatment to the patient
• Better assesment of prognosis
– Therapy evaluation
– Other PET tracers eg. hypoxia tracers especially for RT
Thanks foryour attention!
Respiration gated PET (4-D PET)
4-D PET
Most relevant for peripheral basal nodules with much respiratory movement
12 mm solid nodule in R3; 89 d dobling time,PET positive, surgery T1N0M0
Randomised studies of PET in NSCLC stagingAuthor Patients Design End Point Conclusion
Van Tinteren et al. Lancet 2002; 359:1388-92(PLUS study)
188 (9 centers)Pot. operable. Diagnosis in 50%70% I+II
Conv. vs. Conv.+PET1 yr follow-upMed.scopy in 66% -PET, 73% + PET
No. of Futile thoracotomies #(Cost)
Rel. Reduction of 51%41% (-PET)21% (+PET)(Reduction in Cost)
Herder et al.J Clin Oncol 2006;24(12):1800-6
465 (22 centers)12-19 % benign29-28 % I+II9-11 % IIIa33-32% IIIb+IV
Conv. vs. PET up-front at first presentation.1 yr follow up
No. of non-invasive procedures for staging
Cost and No. of non-invasive procedures similar, Rel. reduction in invasive procedures incl Med.scopies
Viney et al.J Clin Oncol 2004; 22:2357-62
184 (4 centers)Pot. operable. Diagnosis in 100%92% I, 8% II
Conv. vs. Conv.+PETSurgeon decides to do (or not) med.scopy (in 10) and thoracotomy
No. of total thoracotomies
Slightly better staging with PET, No diff. in End Point.Management changed in 13% (+13%)
Lassen U, Mortensen J, BMB Fischer, &DLCG et al. (closed)PERALUST study
220 (4 centers)Potent. operable.
Conv. vs. Conv.+ PET/CTMed.scopy in 100%1 yr follow-up
No. of Futile thoracotomies #
?Data processing