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Role of PET Role of PET-CT in Pulmonary Malignancy

Role of PET Role of PET-CT in Pulmonary Malignancy

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<strong>Role</strong> <strong>of</strong> <strong>PET</strong>-<strong>CT</strong> <strong>in</strong><strong>Pulmonary</strong> <strong>Malignancy</strong>Dr Samart Rajchadara M.D.Wattnosoth HospitalBangkok Medical Center


Progress <strong>of</strong> Disease and Imag<strong>in</strong>gGenetic ProblemMolecular Imag<strong>in</strong>gBiochemical Change<strong>PET</strong>, MRSPhysiological ChangeSPE<strong>CT</strong>, MRIAnatomical ChangeX-ray, US, <strong>CT</strong>, MRI


CLINICAL APPLICATION OF<strong>PET</strong> SCAN ONCOLOGY NEUROLOGY CARDIOLOGY INFE<strong>CT</strong>IOUS DISEASE


F-18- FDG <strong>PET</strong> – Indications Accord<strong>in</strong>g to the 3rd GermanConsensus Conference (GCC) on F-18-FDG <strong>PET</strong> <strong>in</strong> Oncology fourgrad<strong>in</strong>gs <strong>of</strong> F-1818-<strong>PET</strong> <strong>in</strong>dicationswere established(Reske SN, Kozerke J. Eur J Nucl Med 2001; 28: 1707-1723) 1a: Established cl<strong>in</strong>ical i luse 1b: Cl<strong>in</strong>ical use probable 2: Use <strong>in</strong> <strong>in</strong>dividual cases 3: Not yet assessable due to <strong>in</strong>completedata 4: Cl<strong>in</strong>ical use rare


F-18-FDG <strong>PET</strong> - IndicationsPrimary Tumors and Stag<strong>in</strong>g1a• SPN with <strong>in</strong>creasedsurgical risk• Stag<strong>in</strong>g NSCLC• CUP• Stag<strong>in</strong>g head & neck• Stag<strong>in</strong>g <strong>of</strong> oesophagealcancer• Pancreatic cancer1b• SPN without<strong>in</strong>creased surgicalrisk• Bone/s<strong>of</strong>t tissuetumors• Stag<strong>in</strong>g breast cancer• Stag<strong>in</strong>g melanoma• Stag<strong>in</strong>g NHL


F-18- FDG <strong>PET</strong> – IndicationsRestag<strong>in</strong>g – Therapy Control1a Thyroid cancer Colorectal cancer Melanoma Head and neckcancer Lymphoma (NHL) High grade glioma Tumordedifferentiation1b Radioiod<strong>in</strong>epositive lesions<strong>in</strong> thyroid cancer Therapy control<strong>in</strong> colorectalcancer Pancreaticcancer Lymphoma (HD)


TRACER FOR <strong>PET</strong> C-11 acetate N-13ammonia O-15water F-18FDGFDGC-11,N-13,O-15,F-18


SUV Standardized uptake value–Activity concentration <strong>in</strong> tissue(Bq/gm)/ adm<strong>in</strong>istrated activity (Bq)/BW (gm)– Normal value = 0 – 4 or 5.– Usually low <strong>in</strong> lesion < 2 cm.– Glucose concentration, BW, time after<strong>in</strong>jection ,ROI, <strong>in</strong>dividual id <strong>PET</strong> unit


CLINICAL ASPE<strong>CT</strong> OF <strong>PET</strong> Primary stag<strong>in</strong>g . TNM Monitor<strong>in</strong>g therapy Prediction <strong>of</strong> prognosis. Restag<strong>in</strong>g


<strong>PET</strong>/FDG <strong>in</strong> Lung CancerDiagnosis i ; S<strong>in</strong>gle pulmonary nodule (SPN)Stag<strong>in</strong>g ; T N MRestag<strong>in</strong>g; Evaluation <strong>of</strong> recurrence or residual diseaseTherapy monitor<strong>in</strong>g; Early predictor <strong>of</strong> response to chemotherapy; Assess response after neoadjuvant therapy


<strong>PET</strong>/FDG <strong>in</strong> Lung Cancer Prognosis Radiation treatment plann<strong>in</strong>g(<strong>PET</strong>/<strong>CT</strong>)


Diagnosis i SPNCriteria for cancer SUV > 2.5 > mediast<strong>in</strong>al blood pool activityit Any detectable t uptake <strong>in</strong> nodules< 1 cm.


Diagnosis i SPNMeta-analysisanalysis (Gould, JAMA 2001) 450 nodules (> 1 cm., except 8cases)sens. 98%, spec. 83% 1,474lesions (nodules andmasses)sens. 97%, spec. 78%


Diagnosis SPNFalse positiveInfection, <strong>in</strong>flammation,at granulomatousprocessFalse negative (Low SUV value)BAC, carc<strong>in</strong>oid, muc<strong>in</strong>ousadenocarc<strong>in</strong>oma,(mets renal cell ca?)


Diagnosis i SPNROLE <strong>of</strong> FDG/<strong>PET</strong>Intermediate pre test probabilityusually after <strong>in</strong>determ<strong>in</strong>ateresult from <strong>CT</strong> scan (recentlywith dynamic contrast-enhancedhelical l <strong>CT</strong> with wash-<strong>in</strong> andwash-out analysis)a s)


S<strong>in</strong>gle <strong>Pulmonary</strong> Nodule NeoplasmBenignHamatoma, fibroma<strong>Malignancy</strong>Cancer, metastasis, lymphoma,carc<strong>in</strong>oid, Infectious lesions


Study <strong>in</strong> Khon Khan U Benign 50 % Primary cancer 40 % Solitary metastasis 10 %Wipa Reechaipichitkul (วิภา รีชัยพิชิตกุล) 1


SPNThirty-five patients with 36 SPNs < or =10mm <strong>in</strong> diameterIn 13 <strong>of</strong> 14 malignant nodules and <strong>in</strong> two <strong>of</strong> 22 benignnodules, diagnosis was confirmed by histology. Prevalence<strong>of</strong> malignancy was 39%.<strong>PET</strong> imag<strong>in</strong>g correctly identified 30 <strong>of</strong> 36 small lesions.One lesion : false negative on <strong>PET</strong> (<strong>CT</strong>: 10 mm)Five lesions : false positive on <strong>PET</strong> Specificity = 77% (17/22; 95% CI: 0.55-0.92),Sensitivity 93% (13/14; 95% CI: 0.66-1.0),positive predictive value 72% (1313/1818; 95% CI: 0.4646-0.9090)negative predictive value 94% (17/18; 95% CI: 0.73-1.0).2004 Jun3Eur J Nucl Med Mol Imag<strong>in</strong>g. 2004 Sep;3131(9): ):1231-6.Epub


AJR 2006; 187:13611361-13671367Sensitivity%Specificity%PPV%NPV%<strong>CT</strong>enhanced100 29 68 100Q <strong>PET</strong> FDG 98 76 86 93Semi-Q 8484 82 88 78Visual88analysis88 76 85 81


Journal <strong>of</strong> Nuclear Medic<strong>in</strong>e Vol. 48No. 2 214-220 220 2007 <strong>PET</strong> and <strong>CT</strong> correctly characterized31 and <strong>PET</strong>/<strong>CT</strong> correctlycharacterized 39 <strong>of</strong> the 42 lesions asmalignant or benign.<strong>PET</strong> <strong>CT</strong> <strong>PET</strong>-<strong>CT</strong>Accuracy 74% 74% 93%


<strong>CT</strong> 93%/ %/3131% ( sen/spec)<strong>PET</strong> 69%/ %/85%<strong>PET</strong>-<strong>CT</strong>97%/ %/85% There were significant differences (P< 0.05) between <strong>PET</strong>/<strong>CT</strong> and <strong>PET</strong> foraccuracy, sensitivity, and specificity


<strong>in</strong> cases <strong>of</strong> lesions larger than 8 mm- + ve <strong>PET</strong> scan, the likelihood <strong>of</strong> lungcancer is greater than 85%- - ve <strong>PET</strong> scan, the likelihood <strong>of</strong>malignancy is very low (negative predictivevalue greater than 90%)- -ve <strong>PET</strong> scan <strong>in</strong> subcentimeter nodules,follow-up <strong>CT</strong> is needed, s<strong>in</strong>ce there are nodata concern<strong>in</strong>g the negative predictivevalue <strong>of</strong> <strong>PET</strong> <strong>in</strong> this size range.


Is there a role for <strong>PET</strong> <strong>in</strong> theevaluation <strong>of</strong> subcentimeterpulnomary nodules?Kernst<strong>in</strong>e, Sem<strong>in</strong> Thorac Cardiovasc Surg 2005(Review)< 5 mm : Useless5-10mm : Useful <strong>in</strong>formationmight be ga<strong>in</strong>ed <strong>in</strong> those with<strong>in</strong>termediate risk by <strong>CT</strong> (if +ve)If –ve = no <strong>in</strong>formation


Ayesha, Ann Thorac surg 2006585 cases (496malignant) with surg.patho.median maxSUV for malignant 8.5 (0-36)median maxSUV for benign 4.9 (0-28)% malignant- maxSUV 0 - 2.5 24%- maxSUV 2.6 -4.0 80%- maxSUV > 4.0 96%


Stag<strong>in</strong>g:NSCL<strong>CT</strong> stag<strong>in</strong>g (<strong>CT</strong> is more accurate)Differentiate tumor from atelectasisDeterm<strong>in</strong>e presence <strong>of</strong> malignantpleural disease/effusion


<strong>CT</strong> SCAN T1 periphery without t node enlargement : N2 +ve16% N2 disease, chest <strong>CT</strong> scans had sensitivity andspecificity rates <strong>of</strong> 69% and 71%, respectively chest <strong>CT</strong> scan plus mediast<strong>in</strong>oscopy wassignificantly more accurate ( 89% versus 71%)thanus<strong>in</strong>g the chest <strong>CT</strong> scan alone for identify<strong>in</strong>g N2disease. Arita et al : lung cancer metastases to normalsize mediast<strong>in</strong>al lymph nodes : 16% false-negative chest <strong>CT</strong> scans with histologicidentification <strong>of</strong> occult N2 or N3 disease.


<strong>CT</strong> scan The NCCN guidel<strong>in</strong>e panel : overall<strong>CT</strong> chest Sensitivity 40%-6060% Specificity it 45%-9090% False negative <strong>of</strong> stage IA = 21 %. PPV = 43 % NPV = 92%


<strong>PET</strong> scan Sensitivity = 78%Ch<strong>in</strong> et al : mediast<strong>in</strong>al i nodes Specificity ity =81% Negative predictive value <strong>of</strong> 89%


N stag<strong>in</strong>g<strong>CT</strong> <strong>PET</strong>Meta-analysisanalysis sens / spec sens / spec Toloza et al 57% / 82% 84% / 89%(Chest 2003) Gould et al 61% / 79% 85% / 90%(Ann Intern Med 2003)


The size <strong>of</strong> mediast<strong>in</strong>al lymph nodesand its relation with metastatict ti<strong>in</strong>volvement; a meta-analysisanalysisde Langen, Eur J Cardiothorac Surg 2006Cases with enlarged node on <strong>CT</strong>, but –ve <strong>PET</strong>10-1515 mm ; Post test prob. for N2 = 5%16-20mm ; Post test prob. for N2 = 21%


Mediast<strong>in</strong>oscopy is the gold standard d for evaluat<strong>in</strong>gmediast<strong>in</strong>al nodes. T3 lesions even if the <strong>PET</strong>/<strong>CT</strong> scan doesnot suggest mediast<strong>in</strong>al node <strong>in</strong>volvement Used <strong>in</strong> cases <strong>of</strong> mediast<strong>in</strong>al node<strong>in</strong>volvement <strong>in</strong> patients with a positive<strong>PET</strong>/<strong>CT</strong> scan However, <strong>in</strong> patients with peripheral T2,central T1 or T2 lesions with negative<strong>PET</strong>/<strong>CT</strong> scans, the risk for mediast<strong>in</strong>allymph node <strong>in</strong>volvement is higher


ecause <strong>of</strong> the low prior probability<strong>of</strong> lymph node <strong>in</strong>volvement <strong>in</strong>patients with peripheral T1 lesions,some NCCN <strong>in</strong>stitutions do not userout<strong>in</strong>e mediast<strong>in</strong>oscopy <strong>in</strong> thesepatients


Advances <strong>in</strong> <strong>PET</strong> technologyhave <strong>in</strong>creased the need forsurgical stag<strong>in</strong>g g<strong>in</strong> NSCLCLee, J thorac Cardiovasc Surg2007<strong>PET</strong>/<strong>CT</strong> should be used only as anadjunct to cl<strong>in</strong>ical stag<strong>in</strong>g and thatsurgical stag<strong>in</strong>g rema<strong>in</strong>s the goldstandard!!d!!


Stag<strong>in</strong>g:NSCLCM stag<strong>in</strong>g 10-2020% unsuspected sitesComparable sensitivity to bonescan, but more specific for bonemets.More specific than <strong>CT</strong> for adrenalmets.Not very good for bra<strong>in</strong> mets. (sens~85%)


Can <strong>PET</strong>/<strong>CT</strong> substitute for bonesc<strong>in</strong>tigraphy <strong>in</strong> assessment <strong>of</strong>bone metastases <strong>in</strong> lung cancerpatients?


PPV <strong>of</strong> FDG-<strong>PET</strong> = 90% (9595%confidence <strong>in</strong>terval [CI], 69%-9898%)NPV <strong>of</strong> FDG-<strong>PET</strong> = 98% (9595% CI,92%-99%). PPV <strong>of</strong> Bone scan = 35% (95% CI,23%-49%) )and NPV <strong>of</strong> Bone scan = 96% (95% CI,88%-9999%),Bury et al Eur J Nucl Med.1998;25:1244-12471247


145 patients on a lesion-byby-lesionbasis Sensitivity <strong>of</strong> FDG-<strong>PET</strong> = 87.5%Specificity <strong>of</strong> FDG <strong>PET</strong>= 97.3%Sensitivity for bone scans = 81.2%Specificity for bone scans = 74.3% Cheon et al J Nucl Med. 2007;40;40:96.


Bone sc<strong>in</strong>tigraphy showed asensitivity ii i <strong>of</strong> 67% (7/1111) while that <strong>of</strong><strong>PET</strong>/<strong>CT</strong> was 100% (11/11) fordetection <strong>of</strong> bone metastases.39 <strong>of</strong> 95 patients without bonemetastases, the assessment wasfalse-positive for bone sc<strong>in</strong>tigraphybut negative for <strong>PET</strong>/<strong>CT</strong>Journal <strong>of</strong> Cl<strong>in</strong>ical Oncology, 2006 ASCO Annual Meet<strong>in</strong>g Proceed<strong>in</strong>gsPart I. Vol 24, , No. 18S S (June 20 Supplement), 2006: 7203


skeletal l metastases t were detected t d <strong>in</strong> 13% <strong>of</strong>patients, and approximately 75% <strong>of</strong> these patients wereasymptomatic.[ .[10]801.Lau et al : Chest Surg Cl<strong>in</strong> N Am. 2000;10:781- up to 40% <strong>of</strong> patients with proven bonemetastases are asymptomatic.Shreve et al :. Radiology. 1996;199199:751-756756 For these reasons, it is probably useful u toexam<strong>in</strong>e the skeletal system radiographically <strong>in</strong>patients with lung cancer


After chemotherapy


1 year later


Bra<strong>in</strong> metastasisSensitivity = 60 %Specificity = 99 %Positive predictive value = 97 %Negative predictive values = 75 % Radiology Sep 1999; 212; 803-4


Adrenal gl met Adrenal metastases are common and<strong>of</strong>ten solitary. They must bedff differentiated df from adrenaladenomas, which occur <strong>in</strong> 1% <strong>of</strong> theadult population. Lesions smaller than1 cm are usually benign. Metastasesare usually larger than 3 cm; onnonenhanced <strong>CT</strong> scans, they have anattenuation coefficient <strong>of</strong> 10 HU orhigher. Adenomas and metastasescan also be dist<strong>in</strong>guished by us<strong>in</strong>gMRI and <strong>PET</strong>.


Metser et al: J Nucl Med 2006 47:3232-3737 175 adrenal masses <strong>in</strong> 150 pts F<strong>in</strong>al diagnosis based on histology,FU (mean 14 mo) ,morphologicimag<strong>in</strong>g . <strong>PET</strong> study : SUV cut<strong>of</strong>f <strong>of</strong> 3.1 yieled– Sensitivity 98 % ,specificity 92 %– Positive predictive value 89 %– Negative predictive value 98 %


51 <strong>of</strong> 175 masses were 1.5 cm orless <strong>in</strong> diameter. All <strong>of</strong> lesions were correctly classifiedby us<strong>in</strong>g SUV <strong>of</strong> 3.1


Blake et al :MGH Boston Radiology 2006 Mar;238238(3): ):970970-77 41 adrenal masses ,9 malignant and 32benign Malig<strong>in</strong>ant : SUV <strong>of</strong> lesion > SUV <strong>of</strong> liver :4.04(1.5252-1717.0808) Benign : SUV <strong>of</strong> lesion < SUV <strong>of</strong> liver :0.66(0.22-0.9494) Sensitivity 100 % Specificity 93.8 % Positive predictive value 81.8 % Negative predictive value 100 %


Eur J Nucl Med Imag<strong>in</strong>g 2006Jan;33(1):):29-35 80 masses were evaluated by us<strong>in</strong>g<strong>CT</strong> and <strong>PET</strong> <strong>CT</strong> +ve : tumor >4 cm ,HU >30,delayed contrast enhancement <strong>CT</strong> – ve : tumor


Group <strong>of</strong> <strong>CT</strong> + ve and – ve<strong>PET</strong> : sens 100 % ,spec 96 %<strong>CT</strong> : sens 88 % ,spec 100 % Group <strong>of</strong> <strong>CT</strong> undeterm<strong>in</strong>edd<strong>PET</strong> : sens 88 % spec 96 %


Stag<strong>in</strong>gNSCLCImpact <strong>of</strong> <strong>PET</strong>/FDG stag<strong>in</strong>g onmanagementChange stage (mostly upstag<strong>in</strong>g)> change Rx modalities (curative >palliative)> less futile thoracotomy (1/5)Change radiation treatment volumeCost-effectiveness


Advantages <strong>of</strong> <strong>PET</strong>/<strong>CT</strong> More accurate <strong>in</strong> diagnosis andlocalize lesionsesp. nodal metastasisAntoch et al;Radiology 2003<strong>PET</strong> <strong>CT</strong>SensitivitySpecificity<strong>PET</strong>/<strong>CT</strong>89% 70% 89%89% 59% 94% Metabolic radiation treatmentplann<strong>in</strong>gAlter radiation i treatment volume <strong>in</strong>30-60% Metabolic guided biopsy


Thank you


<strong>Pulmonary</strong> metastases t e are commonbecause the entire output <strong>of</strong> the rightheart and the lymphatic system flowthrough the pulmonary vascular system. Fragments <strong>of</strong> tumor are dislodged aftervenous <strong>in</strong>vasion, and they are carried astumor emboli to the lungs via the systemiccirculation. The majority <strong>of</strong> thesefragments lodge <strong>in</strong> the small pulmonaryarteries or arterioles ฝฝฝฝฝฝฝฝThese nodulesare most commonly located eithersubpleurally or <strong>in</strong> the lung bases ratherthan <strong>in</strong> the upper lung,


lymphangitis carc<strong>in</strong>omatosis Less <strong>of</strong>ten, tumor emboli rema<strong>in</strong>conf<strong>in</strong>ed to the perivascular<strong>in</strong>terstitium and spread along thelymphatic channels toward the hilumor lung periphery most <strong>of</strong>ten caused by breast, lung,stomach, ,p pancreatic, or prostatecancer


Age: Risk <strong>of</strong> malignancy <strong>in</strong>creases with age.– Risk <strong>of</strong> 3% at age 35-3939 years– Risk <strong>of</strong> 15% at age 40-4949 years– Risk <strong>of</strong> 43% at age 50-5959 years– Risk <strong>of</strong> greater than 50% <strong>in</strong> persons older than 60 yearsSmok<strong>in</strong>g history: A history <strong>of</strong> smok<strong>in</strong>g <strong>in</strong>creases the chances <strong>of</strong> the SPN be<strong>in</strong>g malignant.Prior history <strong>of</strong> cancer: People with a history <strong>of</strong> cancer <strong>in</strong> other areas <strong>of</strong> the body have a greater chancethat the SPN is malignant.Occupational risk factors for lung cancer: Exposure to asbestos, radon, nickel, chromium, v<strong>in</strong>yl chloride,and polycyclic hydrocarbons <strong>in</strong>creases the chance that the SPN is malignant.Travel history: People who have traveled to areas with endemic mycosis (eg, histoplasmosis,coccidioidomycosis, blastomycosis) or a high prevalence <strong>of</strong> tuberculosis have a higher chance <strong>of</strong> the SPNbe<strong>in</strong>g benign.People who have a history <strong>of</strong> tuberculosis or pulmonary mycosis have a greater chance <strong>of</strong> the SPN be<strong>in</strong>gbenign.

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