standard approach towards patients with metastatic lung cancers is palliative oral chemotherapy with targeted agents . treatment response to these agents is routinely assessed by comparing baseline and post - treatment ct scans , based on response evaluation criteria in solid tumors ( [ recist ] 1.1 ) criteria . however , these being receptor specific therapies , manifestation of response can be best assessed by estimating the metabolic activity of tumor , rather than the size . based on this principle , we aimed at assessing the treatment response on metabolic imaging using fdg pet and comparing it with morphological criteria on ct . patients with metastatic non small cell lung carcinoma ( nsclc ) of lung on targeted therapy who were referred to our department for a pet ct study prior to start of treatment and for a response evaluation after 46 weeks , between june 2010 and june 2013 were included in this retrospective evaluation . written informed consent 31 patients ( 23 males , 8 females ) with metastatic ( nsclc ) of lung who tested positive for epidermal growth factor receptor ( egfr ) were included . these patients received egfr tyrosine kinase ( tk ) inhibitor gefitinib , 250 mg , orally . independent evaluation was done by - contrast - enhanced ct component of pet / ct and pet component of fused 18 f - fdg pet / ct studies , at baseline and at 46 weeks post - therapy . patient characteristics egfr mutation diagnostics were performed in all patients with samples suitable for molecular analysis . patients were asked to fast for 46 h prior to the study and blood glucose levels were checked and confirmed to be < 150 mg / dl . the studies were performed 6090 min following intravenous administration of 5 mbq / kg of 18f - fdg . imaging was performed on a discovery st pet - ct system ( ge medical ) , equipped with a 16 slice ct scanner with a dedicated pet ( bgo crystal , dimensions 3.8 mm  3.8 mm  3.8 cm ) . ct was performed over 5 to 8 eight bed positions from skull base to mid - thigh . ct parameters included 140 kv , 110210 ma , 0.8 s / rotation , pitch of 1.75:1 , field of view [ fov ] of 50 cm , length of scan 1.01.6 m , 0.625 spatial resolution and slice thickness of 3.75 mm . intravenous and oral contrast was routinely administered in all patients , after confirming the serum creatinine levels . pet data was acquired sequentially in the same anatomic locations with 15.4 cm axial fov acquired in 3d ( three - dimensional ) mode with 3 min / bed position . images reconstruction was done using a standard reconstruction algorithm with ordered subset expectation maximization ( osem ) . image fusion was performed using coordinate based fusion software and transferred to the workstation that provided multi - planar reformatted images and displayed pet , ct , and pet - ct fusion images . images were independently interpreted by a nuclear medicine physician and a radiologist who were blinded to each other 's results . ct findings were analyzed using the recist 1.1 and the pet findings by european organization for research and treatment of cancer criteria ( eortc ) criteria . complete response ( cr ) indicates disappearance of all target lesions , partial response ( pr ) as 30% or more decrease in sum of diameters of target lesions , progressive disease ( pd ) as 20% or more increase in sum of diameters of target lesions and also an absolute increase of at least 5 mm and/or appearance of one or more new lesions , stable disease ( sd )  who did not qualify for either sufficient shrinkage to qualify for pr nor sufficient increase to qualify for pd . complete resolution of fdg uptake within the measurable target lesion so that it is indistinguishable from surrounding background , with the appearance of no new lesion , was labeled as complete metabolic response ( cmr ) . reduction of minimum of 1525% of standardized uptake value ( suv ) max in the target volume in the same lesion as the baseline measurement was grouped under partial metabolic response ( pmr ) . progressive metabolic disease ( pmd ) was a more than 25% increase in the suv max of the fdg uptake or appearance of fdg avid new lesion / s that is / are morphologically typical of cancer . stable metabolic disease ( smd ) was disease which did not qualify for cmr , pmr , or pmd . 31 patients ( 23 males , 8 females ) with metastatic ( nsclc ) of lung who tested positive for epidermal growth factor receptor ( egfr ) were included . these patients received egfr tyrosine kinase ( tk ) inhibitor gefitinib , 250 mg , orally . independent evaluation was done by - contrast - enhanced ct component of pet / ct and pet component of fused 18 f - fdg pet / ct studies , at baseline and at 46 weeks post - therapy . patients were asked to fast for 46 h prior to the study and blood glucose levels were checked and confirmed to be < 150 mg / dl . the studies were performed 6090 min following intravenous administration of 5 mbq / kg of 18f - fdg . imaging was performed on a discovery st pet - ct system ( ge medical ) , equipped with a 16 slice ct scanner with a dedicated pet ( bgo crystal , dimensions 3.8 mm  3.8 mm  3.8 cm ) . ct was performed over 5 to 8 eight bed positions from skull base to mid - thigh . ct parameters included 140 kv , 110210 ma , 0.8 s / rotation , pitch of 1.75:1 , field of view [ fov ] of 50 cm , length of scan 1.01.6 m , 0.625 spatial resolution and slice thickness of 3.75 mm . intravenous and oral contrast was routinely administered in all patients , after confirming the serum creatinine levels . pet data was acquired sequentially in the same anatomic locations with 15.4 cm axial fov acquired in 3d ( three - dimensional ) mode with 3 min / bed position . images reconstruction was done using a standard reconstruction algorithm with ordered subset expectation maximization ( osem ) . image fusion was performed using coordinate based fusion software and transferred to the workstation that provided multi - planar reformatted images and displayed pet , ct , and pet - ct fusion images . images were independently interpreted by a nuclear medicine physician and a radiologist who were blinded to each other 's results . ct findings were analyzed using the recist 1.1 and the pet findings by european organization for research and treatment of cancer criteria ( eortc ) criteria . complete response ( cr ) indicates disappearance of all target lesions , partial response ( pr ) as 30% or more decrease in sum of diameters of target lesions , progressive disease ( pd ) as 20% or more increase in sum of diameters of target lesions and also an absolute increase of at least 5 mm and/or appearance of one or more new lesions , stable disease ( sd )  who did not qualify for either sufficient shrinkage to qualify for pr nor sufficient increase to qualify for pd . complete resolution of fdg uptake within the measurable target lesion so that it is indistinguishable from surrounding background , with the appearance of no new lesion , was labeled as complete metabolic response ( cmr ) . reduction of minimum of 1525% of standardized uptake value ( suv ) max in the target volume in the same lesion as the baseline measurement was grouped under partial metabolic response ( pmr ) . progressive metabolic disease ( pmd ) was a more than 25% increase in the suv max of the fdg uptake or appearance of fdg avid new lesion / s that is / are morphologically typical of cancer . stable metabolic disease ( smd ) was disease which did not qualify for cmr , pmr , or pmd . 31 patients of metastatic lung cancers , on targeted therapy underwent contrast enhanced pet ct were assessed using recist 1.1 new recist 1.1and eortc criteria , respectively [ table 2 ] . concordance [ figure 1 ] in response to targeted therapy was seen in 26 ( 83.4% ) out of 31 patients , on metabolic and morphological criteria . of these 26 patients , 4 patients showed pr / pmr , 10 patients showed sd / smd and 12 patients showed pd / pmd . arrow ) and metabolic activity ( max suv ) ( 1c , and d  arrow ) seen on both axial ct component and axial fused pet / ct component , respectively ; thus , partial response ( pr ) on recist is concordant with partial metabolic response ( pmr ) , according to eortc criteria discordance in response to targeted therapy was seen in 5 ( 16.6% ) patients . all the three patients showed complete metabolic and morphological regression in metastatic sites , namely in left supraclavicular nodes [ figure 2 ] in two patients and contralateral nodule in one patient . however , at the primary site , ct images showed no significant change in size follow - up imaging either with ct or pet / ct after 2 months showed no further change in disease status . there is no significant interval change in size on axial ct images ( 2b and e  arrow ) . however , coronal maximum intensity projection ( mip ) ( 2a and d  arrow ) and axial fused pet / ct ( 2c and f arrow ) images show significant regression in metabolic activity coronal mip ( 2a  arrowhead ) also demonstrates tracer uptake in left supraclavicular node ( arrowhead ) , which completely regresses on post - treatment mip image . thus stable disease ( sd ) on recist is discordant with eortc criteria , which show partial metabolic response ( pmr ) two patients showed sd on recist 1.1 and pmd on eortc metabolic criteria . new focal fdg avid marrow lesions [ figure 3 ] were seen in both these cases , whereas ct images were unremarkable , thus making the disease status as sd on recist 1.1 and pmd on eortc criteria . baseline and post gefitinib axial ct ( 3a and d ) and fused pet / ct ( 3b and e ) images in soft tissue window show no interval change in size and metabolic activity of primary lung mass . focal fdg uptake in the marrow of right pubic bone ( 3f  arrow ) is a new finding however , axial ct - baseline and post - treatment images in bone window show no demonstrable lesion , thus patient has stable disease ( sd ) by recist . however , new hypermetabolic metastatic marrow lesion is suggestive of progressive metabolic disease ( pmd ) on eortc criteria follow - up imaging either with ct or pet / ct after 2 months in these patients showed further metabolic and morphological disease progression . concordance [ figure 1 ] in response to targeted therapy was seen in 26 ( 83.4% ) out of 31 patients , on metabolic and morphological criteria . of these 26 patients , 4 patients showed pr / pmr , 10 patients showed sd / smd and 12 patients showed pd / pmd . there is significant reduction in size ( 1a and , b  arrow ) and metabolic activity ( max suv ) ( 1c , and d  arrow ) seen on both axial ct component and axial fused pet / ct component , respectively ; thus , partial response ( pr ) on recist is concordant with partial metabolic response ( pmr ) , according to eortc criteria discordance in response to targeted therapy was seen in 5 ( 16.6% ) patients . of these all the three patients showed complete metabolic and morphological regression in metastatic sites , namely in left supraclavicular nodes [ figure 2 ] in two patients and contralateral nodule in one patient . however , at the primary site , ct images showed no significant change in size follow - up imaging either with ct or pet / ct after 2 months showed no further change in disease status . there is no significant interval change in size on axial ct images ( 2b and e  arrow ) . however , coronal maximum intensity projection ( mip ) ( 2a and d  arrow ) and axial fused pet / ct ( 2c and f arrow ) images show significant regression in metabolic activity coronal mip ( 2a  arrowhead ) also demonstrates tracer uptake in left supraclavicular node ( arrowhead ) , which completely regresses on post - treatment mip image . thus stable disease ( sd ) on recist is discordant with eortc criteria , which show partial metabolic response ( pmr ) two patients showed sd on recist 1.1 and pmd on eortc metabolic criteria . new focal fdg avid marrow lesions [ figure 3 ] were seen in both these cases , whereas ct images were unremarkable , thus making the disease status as sd on recist 1.1 and pmd on eortc criteria . baseline and post gefitinib axial ct ( 3a and d ) and fused pet / ct ( 3b and e ) images in soft tissue window show no interval change in size and metabolic activity of primary lung mass . focal fdg uptake in the marrow of right pubic bone ( 3f  arrow ) is a new finding however , axial ct - baseline and post - treatment images in bone window show no demonstrable lesion , thus patient has stable disease ( sd ) by recist . however , new hypermetabolic metastatic marrow lesion is suggestive of progressive metabolic disease ( pmd ) on eortc criteria follow - up imaging either with ct or pet / ct after 2 months in these patients showed further metabolic and morphological disease progression . tk inhibitors like gefitinib targeting the egfr can improve progression - free survival ( pfs ) and overall survival ( os ) in receptor positive patients with these cancers . moreover , translational studies have shown that 18f - fdg uptake decreased within 2 h in h3255 cell lines having egfr mutations after incubation with 0.2 mm of gefitinib . this was due to translocation of glucose transporters from the cell membrane to the cytoplasm . similar results were seen on 18f - fdg tumor uptake in animal experiments after only two doses of gefitinib . this forms the molecular basis of the utility of fdg pet for assessing response to targeted therapy , especially in receptor positive lung cancers . it is well - known that metabolic response demonstrated by fdg pet - ct well precedes the anatomic response and has been well - documented in the existing literature . metabolic response on pet is manifested by decrease in the glycolytic activity of tumor , whereas anatomic response criteria which are based on size of the tumor , lag weeks and months behind the metabolic response . conventionally , nsclc is an fdg avid tumor and pet / ct is routinely indicated for staging this cancer . hence , metastatic burden can be assessed and depending on egfr status , metastatic cancers can be subjected to targeted therapy . the clinical end point of the targeted agents is to achieve a prolonged stable disease rather than tumor shrinkage . thus , lack of progression is associated with good improvement in outcome , even in the absence of partial or complete response . as a result , standard size - based assessment of response to these therapies using recist underestimates therapeutic activity . this forms the basis of use of metabolic parameters using pet for treatment response assessment . criteria for metabolic response assessment have been evolving and improving  with pet response criteria in solid tumors ( percist ) criteria being followed in all recent studies . compared eortc and percist criteria for response assessment in metastatic colorectal cancer , concluding that both criteria gave similar response and survival outcomes with good agreement . metabolic response on pet also impacts the survival statistics in patients with metastatic lung cancer ; patients with progressive metabolic disease ( pmd ) on post - treatment pet study showing shorter time to progression and overall survival ( os ) compared to patients with smd or with partial pmr or complete cmr metabolic response . our data , though in a small cohort of three patients with pmd on fdg pet showed similar results . in addition , early assessment on fdg pet is also a predictor of response to targeted therapy ; pmd suggestive of refractoriness of targeted agents in spite of egfr receptor positivity . early prediction of therapeutic failure not only warrants change of treatment , but also avoids unnecessary expenditure and potential toxicity . our study highlights the utility of metabolic imaging in metastatic lung cancers , not only for treatment effectiveness of therapy , but also for early assessment of refractoriness . though the number of patients is limited , results obtained warrant further assessment with a larger cohort . furthermore , in addition to follow - up imaging , survival statistics would make the study more robust . metabolic criteria using pet / ct could accurately predict response as well as disease progression early in the course of targeted therapy , compared to morphologic criteria on ct scan . hence , functional imaging with fdg pet provides a more definitive evidence of response to targeted therapy and disease status , unlike conventional anatomical imaging .
introduction : targeted therapeutic agents are indicated in metastatic lung cancers . 
 these being receptor specific therapies , manifestation of response can be best assessed by estimating the metabolic activity of tumor , rather than the size . 
 this retrospective analysis studied metabolic and morphological response on positron emission tomography ( pet ) and computed tomography ( ct ) , respectively to these agents.materials and methods : thirty - one patients ( 23 males , 8 females with an age range of 4277 years ) with epidermal growth factor receptor ( egfr ) positive metastatic lung cancer on gefitinib , who underwent pet / ct , at baseline and at 46 weeks , were assessed by response evaluation criteria in solid tumors [ recist ] 1.1 and european organization for research and treatment of cancer ( eortc ) criteria.results:concordance between recist 1.1 and eortc was seen in 26 ( 83.7% ) patients . 
 discordance was seen in 5 ( 16.3% ) patients . in patients with discordance , 
 the results were confirmed by follow - up imaging . 
 metabolic eortc criteria changed the disease status from stable disease to partial response ( 3 out of 5 ) and progressive disease ( 2 out of 5 ) in these five patients.conclusions:metabolic criteria using pet / ct could accurately predict response as well as disease progression early in the course of targeted therapy , compared to morphologic criteria . 
 in addition , early metabolic response assessment can predict refractoriness of therapy .