Is FDG-PET/CT useful for managing malignant pleural mesothelioma?

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1 16 ORIGINAL Is FDG-PET/CT useful for mnging mlignnt pleurl mesotheliom? Hideki Otsuk, Kori Terzw, Nomi Morit, Yoichi Otomi, Kyo Ymshit, nd Hiromu Nishitni Deprtment of Rdiology, Institute of Helth Biosciences, the University of Tokushim Grdute School, Tokushim, Jpn Astrct : Ojective : Imging techniques such s CT, MRI nd PET/CT hve essentil prend post-tretment roles in detecting tumors nd evluting the extension of mlignnt pleurl mesotheliom (MPM). We sough to evlute the dvntges nd limittions on FDG-PET/CT findings. Ptients nd Methods : We performed 13 FDG-PET/CT studies in 9 ptients with MPM (8 mles, 1 femle, ged 51 to 84 yers, 9 t the initil dignosis, 4 follow up studies). We reviewed FDG-PET/CT findings of primry tumors, recurrent tumors, lymph nodes, metstsis. Results : All primry nd recurrent tumors were FDG positive. The uptke ptterns t initil dignosis were ; diffuse+multi-nodulr uptke pttern in 5, diffuse irregulr thickened uptke pttern in 2, some focl thickened pttern in one, nd slight diffuse uptke pttern in one. Two of the 3 ptients dignosed s N0 y PET nd operted on hd negtive lymph nodes confirmed pthologiclly. The other ptient dignosed s N0 y PET, who hd one month of time lg etween PET/CT exmintion nd surgery, ws confirmed s N2 y extrpleurl pneumonectomy. In 3 ptients, hilr or medistinl lymph nodes were difficult to distinguish from irregulr pleurl thickening. One ptient hd FDG positive lymph node in the ipsilterl suprclviculr region confirmed s metstsis (N3). One ptient hd FDG positive lymph node in the pr-ortic region. Lung metstsis ws seen in one ptient (M1). In nother ptient, two focl nodulr uptkes in the colon were detected nd confirmed s colon polyps (pthologiclly Group 3-4). At restging, 3 of 4 ptients showed diffuse+multi-nodulr uptke nd one ptient showed multi-nodulr uptke. Conclusions : The utility of FDG-PET/CT is limited for evlution of primry tumor extension nd nodl sttus. FDG-PET/CT is useful for detecting distnt metstsis nd for evluting ctivity in suprclviculr or dominl lymph nodes. It is lso useful for identifying unsuspected diseses. J. Med. Invest. 56 : 16-20, Ferury, 2009 Keywords : mlignnt pleurl mesotheliom, FDG-PET/CT INTRODUCTION FDG-PET/CT cn demonstrte tumor metolism Received for puliction Septemer 10, 2008 ; ccepted Novemer 14, Address correspondence nd reprint requests to Hideki Otsuk, Deprtment of Rdiology, Institute of Helth Biosciences, the University of Tokushim Grdute School, Kurmoto- cho, Tokushim , Jpn nd Fx : nd morphology in single session. Thus it hs n importnt role in tumor imging. PET/CT is lso useful to differentite mlignnt from enign lesions, define stging, detect recurrence t n erly stge, nd monitor therpeutic effects. Mlignnt pleurl mesotheliom (MPM), which rises from the pleur nd is the mostly ssocited with sestos exposure, is common neoplsm of mesothelil cells (1). MPM usully develops The Journl of Medicl Investigtion Vol

2 The Journl of Medicl Investigtion Vol. 56 Ferury yers fter exposure to sestos. It cn occur from direct occuptionl exposure s well s from indirect exposure. Its incidence hs een incresing. Histologiclly, MPM is clssified into three types : epithelil (60%), iphsic (30%), nd srcomtous (10%) types (2). The epithelil type is the most common nd hs the est prognosis. MPM is very ggressive disese nd invdes to the chest wll, medistinum, nd diphrgm. MPM lso metstsizes to hilr nd medistinl lymph nodes. Distnt metstses occur in pproximtely 10-20% of ptients. Imging exmintions re necessry for mngement of MPM ptients. We report our experience of FDG-PET/CT in MPM ptients. Four ptients hd only chemotherpy, nd 2 ptients refused ny tretment. All ptients fsted for t lest 4 hours efore the PET/CT scn nd lood glucose levels were checked s eing 150 mg/dl t the time of injection. 18F-FDG (3.7 MBq/kg of ody weight) ws dministered intrvenously using n utomtic injection system. After FDG injection, ptients rested on ed for one hour. Tlking, wlking, or other physicl ctivities were prohiited to reduce unnecessry muscle uptke. One hour fter injection, imges were otined using PET/CT mchine equipped 16-slice multi-detector row CT. We reviewed FDG-PET/CT findings of primry tumors, recurrent tumors, lymph nodes, metstses. PATIENTS AND METHODS A Summry of the ptients is shown in Tle 1. We performed 13 FDG-PET/CT studies in 9 ptients with MPM (8 mles, 1 femle, ged 51 to 84 yers, 9 t the initil dignosis, 4 follow up studies). Five ptients hd history of sestos exposure (56%). Three of the 9 ptients hd extrpleurl pneumonectomy nd chemotherpy/rdition therpy. RESULTS All primry nd recurrent tumors were FDG positive. The uptke ptterns of the 9 ptients t initil dignosis were ; diffuse+multi-nodulr uptke pttern in 5, diffuse irregulr thickened uptke pttern in 2, some focl thickened pttern in one, nd slight diffuse uptke pttern in one. Two of the 3 ptients dignosed s N0 y PET nd operted on hd negtive lymph nodes confirmed pthologiclly. Tle 1 A summry of the ptients. Initil dignosis ge gender sestos uptke exposure pttern Histlogy ctnm ptnm SUVmx other findings Tretment outcome pt.1 61 m + DMN epithelioid susp. T2N0M0 not confirmed 5.4 chemo ded pt.2 60 m - DMN epithelioid T3N2M1 not confirmed 8.1 prortic LN+ no (ptient refused) ded pt.3 59 m + DMN epithelioid T3N0M0 T3N0M EPP+chemo ded pt.4 56 m + DMN iphsic T3N2M0 T3N2M chemo ded pt.5 55 m + DMN iphsic T3N0M0 T3N0M0 3.7 colon polyp EPP+RT live pt.6 84 m + DI uncertin T3N0M0 not confirmed 6.2 no (ptient refused) ded pt.7 77 f - DI iphsic T4N2M0 not confirmed 11.8 chemo ded pt.8 59 m - FT epithelioid T2N0M1 T2N0M1 3.1 lung mets chemo live pt.9 51 m - SLD epithelioid T1N0M0 T3N2M0 1.7 EPP+chemo+RT ded Follow up Tretment time fter 1st PET uptke pttern SUVmx pt.1 chemo 3 mo DMN locl recurrence, suclviculr LN+ 7.4 pt.3 EPP+chemo 5 mo MN locl recurrence 13.2 pt.5 EPP+RT 1 mo DMN progressed disese 5.2 pt.9 EPP+chemo+RT 9 mo DMN locl recurrence 6.2 DMN : diffuse multi-nodulr, DI : diffuse irregulr, FT : focl thickening, SLD : slight diffuse, MN : multi-nodulr EPP : extrpleurl pneumonectomy, RT : rdition therpy

3 18 H. Otsuk, et l. FDG-PET/CT of mesotheliom The other ptient dignosed s N0 y PET, hd one month time lg etween PET/CT exmintion nd surgery, ws confirmed s N2 y extrpleurl pneumonectomy. In 3 ptients, hilr or medistinl lymph nodes were difficult to distinguish from irregulr pleurl thickening. One ptient hd FDG positive lymph node in the ipsilterl suprclviculr region confirmed s metstsis (N3). One ptient hd FDG positive lymph node in the pr-ortic region. Lung metstsis ws seen in one ptient (M1). In nother ptient, two focl nodulr uptkes in the colon were detected nd confirmed s colon polyps (Group 3-4). At follow up studies (1-9 months fter first PET/ CT), locl recurrence nd disese progression ws demonstrted s FDG positive. Three of 4 ptients hving follow up scns showed diffuse+multi-nodulr uptke while the other showed multi-nodulr uptke. No FDG positive lymph node ws seen in the contrlterl hilr nd suprclviculr region. There ws no evidence of distnt metstsis. Ptient 5 (Fig. 2) : A 55 yer-old mle with history of sestos exposure ws dmitted with dyspne. FDG-PET/CT demonstrted diffuse nd multinodulr uptke in the right pleur. No hilr or medistinl lymph node normlities or distnt metstsis were seen (N0 on FDG-PET/CT). He underwent n extrpleurl pneumonectomy nd pt3n0 ws confirmed. Two focl uptkes were demonstrted in the pelvis corresponding to the rectum. Following our recommendtion of colon fierscopic exmintion, these uptkes confirmed s colon polyps (group 3-4). CASE PRESENTATION Ptient 7 (Fig. 1) : A 77 yer-old femle with no history of direct sestos exposure ws dmitted with left pleurl effusion nd pleurl thickening. FDG-PET/CT clerly demonstrted intense diffuse thickened FDG uptke. It ws difficult to differentite pleurl lesion from hilr lymph node metstsis. c d c Fig. 2 Fifty-five yer-old mle. ) MIP imge of FDG-PET. ) Axil view of PET. c) Axil view of CT. d) Axil view of PET/ CT. FDG- PET/CT demonstrted diffuse nd multi- nodulr uptke in the right pleur. No hilr or medistinl lymph node normlities nd no distnt metstsis were seen. A focl uptke is demonstrted in the pelvis corresponding to the rectum (rrow), confirmed s polyp (group 4). Fig. 1 Seventy-seven yer-old femle. ) MIP imge of FDG- PET. ) Axil view of PET/CT. c) Coronl view of PET/CT. FDG-PET/CT clerly demonstrted intense diffuse FDG uptke in thickened pleur. It is difficult to differentite pleurl lesion from hilr lymph node metstsis. No FDG positive lymph node ws seen in the contrlterl hilr nd suprclviculr region. There ws no evidence of distnt metstsis. Ptient 9 (Fig. 3) : A 51 yer-old mle with no history of sestos exposure ws dmitted with prolonged right pleurl effusion. FDG-PET/CT demonstrted slight diffuse uptke long the pleur. There ws no evidence of lymph node metstsis or distnt metstsis. His disese progressed very rpidly nd extrpleurl pneumonectomy one month fter PET/CT exmintion confirmed pt3n2. After 10 months, follow up PET/CT study clerly demonstrted recurrent lesions s FDG positive.

4 The Journl of Medicl Investigtion Vol. 56 Ferury Fig. 3 Fifty-one yer-old mle. ) PET imge t initil dignosis. FDG- PET/CT demonstrted slight diffuse uptke long the pleur. There ws no evidence of lymph node metstsis or distnt metstsis. His disese progressed very rpidly nd extrpleurl pneumonectomy one month fter PET/CT exmintion confirmed pt3n2. ) PET imge t follow up (10 months fter 1 st PET/CT). Recurrent lesions show FDG positive (rrow). DISCUSSION MPM is very rpidly progressing disese nd esily invdes to djcent structures such s the chest wll, medistinum, nd diphrgm. Lymph node metstses nd/or distnt metstses cn occur to orgns such s lungs, liver, drenl glnds, nd rin. Prognosis is relted to the extent of the primry tumor nd metstses. Stge I nd II ptients cn e cndidtes for surgery, while stge III nd IV ptients re considered unresectle. Surgery (extrpleurl pnemonectomy, pleurectomy/ decortiction), rdition therpy, chemotherpy or their comintion is often performed ut the overll survivl is low (3-5). Imging techniques such s CT, MRI nd PET/CT hve essentil pre- nd post-tretment roles in detecting tumors nd evluting the extension of MPM (6). CT is the most widely used modlity, ut tends to underestimte tumor invsion nd lymph node metstses (7, 8). MRI is superior for evluting tumor involvement (9). Perfusion CT or perfusion MRI cn demonstrte tumor microvsculture, while perfusion MRI is used to ssess the effects of tretment (10). There re lso reports concerning the utility of FDG-PET or FDG-PET/CT (6, 11, 12). PET my predict survivl of MPM ptients, nd cn detect extrthorcic metstses ; thus ssisting tretment plnning. By using the uptke chnges of FDG, PET cn monitor the response to chemotherpy (13). However, the utility of PET is limited for T nd N stging with sensitivity reported to e 19% nd 11%, respectively (12). It is sometimes difficult to evlute MPM invsion to djcent structures such s chest wll or medistinum. FDG ccumultes not only in the tumor ut lso in n inflmmtory lesion of sestos relted pleuritis. In one of our ptient (Ptient 9), slight unilterl uptke ws seen in the slightly thickened pleur. This ptient hd pneumonectomy one month fter the PET/CT exmintion. pt3n2 ws confirmed t surgery, nd PET/CT demonstrted recurrence 9 months fter surgery. This showed the ggressive nture of MPM nd the usefulness of PET/CT to evlute recurrent MPM. For N stging, it is sometimes difficult to distinguish hilr or medistinl lymph node metstses from pleurl tumor or irregulr pleurl thickening. Flse-negtive lymph nodes nd flse-positive FDG uptke in medistinl nodes is frequently seen. In this study, hilr or medistinl lymph node enlrgement could not e differentited from irregulr pleurl thickening in 3 of the 9 ptients. On the other hnd, FDGpositive lymph nodes in the suprclviculr nd prortic regions were clerly demonstrted. PET/CT ws useful to detect lung metstsis nd unsuspected disese (colon polyps). We were lso le to use intense FDG uptke s lndmrk for iopsies. In follow up studies, recurrent tumors clerly showed s FDG positive. We clssified uptke pttern in 4 types. The reltionship etween the uptke pttern nd histopthologicl type, nd ptient outcome could not een clrified in our smll numer of ptients ; however, we need to know the uptke pttern nd tht MPM in the erly stge cn show slight lterlity of pleurl uptke. FDG-PET/CT is useful for detecting distnt metstsis nd for evluting ctivity in suprclviculr or dominl lymph nodes. It is lso useful for identifying unsuspected diseses. It is importnt for clinicins to know the dvntges nd limittions of vrious imging modlities for mngement of MPM ptients. REFERENCES 1. Roinson BWS, Lke RA : Advnces in Mlignnt Mesotheliom. N Engl J Med 353(15) : , WHO : Histologicl typing of lung nd pleurl

5 20 H. Otsuk, et l. FDG-PET/CT of mesotheliom tumors. 3 rd Ed, Springer, Berlin, Flores RM, Pss HI, Seshn VE, Dycoco J, Zkowski M, Crone M, Bins MS, Rusch VW : VW. Extrpleurl pneumonectomy versus pleurectomy/decortiction in the surgicl mngement of mlignnt pleurl mesotheliom : results in 663 ptients. J Thorc Crdiovsc Surg 135(3) : 620-6, Flores RM, Krug LM, Rosenzweig KE, Venktrmn E, Vincent A, Heeln R, Akhurst T, Rusch VW : Induction chemotherpy, extrpleurl pneumonectomy, nd postopertive high-dose rdiotherpy for loclly dvnced mlignnt pleurl mesotheliom : phse II tril. J Thorc Oncol 1(4) : , Yjnik S, Rosenzweig KE, Mychlczk B, Krug L, Flores R, Hong L, Rusch VW : Hemithorcic rdition fter extrpleurl pneumonectomy for mlignnt pleurl mesotheliom. Int J Rdit Oncol Biol Phys 56(5) : , Ymmoto M, Gerudo VH, Gill RR, Jcoson FL, Sugrker DJ, Htu H : Morphologic nd functionl imging of mlignnt pleurl mesotheliom. Eur J Rd 64 : , Roch HD, Dvies GJ, Attnoos R, Crne M, Adms H, Phillips S : Asestos : when the dust settles n imging review of sestos-relted disese. Rdiogrphics 22 : S167-84, Lorenzo B, Ferglli B, Scco R, Merlino B, Storto ML : Mlignnt pleurl disese. Eur J Rdiol 34(2) : , Heeln RT, Rusch VW, Begg CB, Pnicek DM, Crvelli JF, Eisen C : Stging of mlignnt pleurl mesotheliom : comprison CT nd MR imging. Am J Roentgenol 172 (4) : , Giesel FL, Bischoff H, von Tengg-Koligk H : Dynmic contrst-enhnced MRI of mlignnt pleurl mesotheliom : fesiility study of noninvsive ssessment, therpeutic follow-up, nd possile predictor of improvement outcome. Chest 129 (6) : , Flores RM, Akhurst T, Gonen M, Zkowski M, Dycoco J, Lrson SM, Rusch VW : Positron emission tomogrphy predicts survivl in mlignnt pleurl mesotheliom. J Thorc Crdiovsc Surg 132(4) : 763-8, Flores RM, Akhurst T, Gonen M, Lrson SM, Rusch VW : Positron emission tomogrphy defines metsttic disese ut not locoregionl disese in ptients with mlignnt pleurl mesotheliom. J Thorc Crdiovsc Surg 126(1) : 11-6, Ceresoil GL, Chiti A, Zucli PA : Erly response evlution in mlignnt pleurl mesotheliom y positron emission tomogrphy with [18F] fluorodeoxyglucose. J Clin Oncol 24 : , 2006