radiotherapy plays an important role in the treatment of thoracic cancers , such as non - small - cell lung cancer ( nsclc ) , small - cell lung cancer ( sclc ) , and esophageal cancer [ 1 , 2 ] .
recent advances in accurate diagnosis improve the practice of curative radiotherapy , because patients with unsuspected metastases may avoid unnecessary local therapies and receive necessary systemic treatment .
accurate delineation of tumor volume is also important to prevent geographic misses in treatment planning .
currently , treatment planning is based on computed tomography ( ct ) imaging to contour the tumor .
tumor delineation is manually performed by each radiation oncologist in clinical practice , which leads to interobserver variability in tumor delineation .
accurate delineation of tumor volume requires the identification of anatomic borders of tumors based on accurate diagnosis .
f-18 fluorodeoxyglucose positron emission tomography ( fdg - pet ) and pet / ct have been reported to enable accurate staging and to detect the tumor extension compared with ct alone .
fdg - pet imaging has many potential advantages in radiotherapy planning , because it can add biological information combined with anatomical information by ct imaging .
radiotherapy planning based on fdg - pet is expected to decrease the interobserver variability amongst thoracic radiation oncologists .
in addition to accurate staging , fdg - pet has the potential to improve radiotherapy planning by its precise delineation of primary tumor and lymph nodes .
indeed , fdg - pet has been investigated as tracer for radiotherapy planning in many cancer types . in this paper , we focus on the role of fdg - pet in radiotherapy for thoracic cancers , including nsclc , sclc , esophageal cancer , and breast cancer .
accurate staging is crucial for lung cancer patients because treatment strategy and prognosis drastically differ according to clinical stage .
ct imaging contributes to the initial determination for the staging of nsclc and provides morphologic information of the disease extension .
currently , fdg - pet is performed to diagnose the stage and evaluate the effects of the treatment in clinical use for nsclc patients .
one of the important roles of fdg - pet is to detect unsuspected lymph nodes or extrathoracic metastases [ 5 , 6 ] .
a prospective study has reported that fdg - pet detected unsuspected metastasis in 20% of candidates for radical radiotherapy , changing their treatment strategies .
furthermore , the same authors showed that early mortality rate was low in patients staged by fdg - pet compared with those staged by conventional imaging , on the basis of their accurate staging .
another prospective study demonstrated that curative radiotherapy in 27% of patients was not qualified by fdg - pet because of distant metastasis or extensive locoregional disease . in this study , 32% of patients
also reported that fdg - pet altered radiation planning in over 50% of patients staged by ct imaging , due to the detection of unsuspected nodal disease , metastatic disease , or tumor extension from atelectasis .
as seen in these findings , the incorporation of fdg - pet improves the accuracy of staging and patient selection , providing better treatment strategy including radiotherapy planning .  
fdg - pet is increasingly performed to define tumor volume for radiotherapy in patients with nsclc .
accurate contouring of organs is important for radiotherapy and pet imaging is currently expected to be useful in the delineation of gross tumor volume ( gtv ) . in this section
several methods have been examined for gtv delineation after the introduction of fdg - pet ( table 1 ) [ 1225 ] .
however , this method arbitrarily depends on the window levels set of the pet images .
several articles have reported the use of standardized uptake volume ( suv ) in gtv identification .
hong et al . compared target volume delineation by fdg - pet with that by ct imaging in 19 patients with nsclc , concluding that suv of 2.5 should be used for radiotherapy planning in nsclc patients .
erdi et al . analyzed a phantom with lung lesion by source - to - background ratios .
they applied this data to 10 patients with 17 primary or metastatic lung lesions , concluding that the source - to - background ratio was useful in the definition of tumor volumes .
compared gtvs obtained from four different methods : visually ( gtvvis ) , applying a 40%-threshold of suv max ( gtv40 ) , using an autocontour of suv 2.5 ( gtv2.5 ) , and using an algorithm by phantom measurements ( gtvbg ) in 25 patients with nsclc . in the results , gtvvis , gtv2.5 , and gtvbg were relevant to the ct - derived gtv , whereas gtv40 appeared unsuitable for target volume delineation .  
recently , some studies reported a new gradient - based method relied on the water shed transform and hierarchical cluster analysis .
this method provided denoised and deblurred images with an edge - preserving filter and a constrained iterative deconvolution algorithm , leading a better estimation of the gradient intensity .
wanet et al . compared a gradient - based segmentation method , a source - to - background ratio method , and a 40% to 50% of suv max method with surgical specimens of 10 patients with nsclc .
all patients underwent image inspections before surgery . among several methods , the gradient - based method achieved the best results , with the lowest average error and smallest standard deviation .
werner - wasik et al . conducted the same experiment using the digital thorax phantom and evaluated the accuracy and consistency of three methods : gradient - based pet segmentation , manual , and constant threshold methods .
they concluded that the gradient - based method was the most accurate with the least systematic bias at any phantom size .   despite these several techniques for the delineation of tumor volume
having been reported in recent years , a gold standard method has not been established to contour gtv automatically . however , fdg - pet has the additional information that aids radiation oncologists to delineate gtv , indicating that fdg - pet should be utilized when tumor volume is delineated in nsclc patients .
interobserver variability in regard to gtv definition is a serious problem in the treatment planning for nsclc [ 26 , 27 ] .
prospectively evaluated the role of fdg - pet in interobserver variability in 30 nsclc patients .
three radiation oncologists contoured gtv using ct alone or fdg - pet registered ct ( pet / ct ) . the mean coefficient of variation for gtv based on pet / ct was significantly smaller than ct alone ( p < 0.01 ) .
recently , van barrdwijk et al . also reported that pet / ct - based autocontouring decreased interobserver variability in delineation of the primary tumor and nodal legions .
these studies indicated that fdg - pet can reduce interobserver variability in radiotherapy treatment planning .  
currently , more patients have been treated by stereotactic body radiotherapy ( sbrt ) for early - stage nsclc [ 1 , 2 ] .
recent studies reported the role of fdg - pet in sbrt for nslcl , such as staging , treatment response , and planning .
henderson et al . performed serial planned fdg - pet ( before and after sbrt ) in stage i nsclc patients treated by 6066  gy in three fractions . in their study , substantial proportion of patients had moderately elevated suvmax at 52 weeks after sbrt without evidence of local failure , suggesting that slight elevation of suvmax should not be surrogate for local failure .
performed sbrt that consisted of 35 fractions with 715  gy per fraction in 92 stage i nsclc patients .
the authors concluded that elective irradiation can safely be omitted in stage i nsclc after accurate nodal staging with pet - ct .  
takeda et al . evaluated the correlation between pretreatment suvmax on fdg - pet and local recurrence in 95 patients with nsclc .
two - year local recurrence rates for lower suvmax ( < 6.0 ) and higher suvmax ( 6.0 ) were 93% and 42% , respectively ( p < 0.001 ) .
multivariate analysis showed that only the suvmax of a primary tumor was a significant predictor for local recurrence ( p = 0.002 ) .
the authors concluded that a high suvmax might be considered for dose escalation to improve local control in nsclc .
hoopes et al . also reported that 58 patients with medically inoperable stage i nsclc treated by sbrt .
total doses ranged from 24 to 72  gy in three fractions . in their study , pretreatment suvmax did not predict three - year overall survival or local control .
coon et al . performed sbrt with a dose of 60  gy in three fractions for stage i nsclc ( n = 26 ) , recurrent lung cancer ( n = 12 ) , and solitary lung metastases ( n = 13 ) .
pet - ct was valuable in staging , treatment planning , but no correlations were found between pretreatment suvmax and treatment response , disease progression - free survival , and overall survival .  
these findings suggest that fdg - pet is useful for accurate staging and treatment planning in stage i nsclc treated by sbrt .
however , it has been controversial whether pretreatment suvmax is prognostic factor for treatment outcomes , such as local control and overall survival .
prospective studies are warranted to establish the role of fdg - pet in sbrt for nsclc patients . for patients with nsclc , local failure after radiation therapy is a significant issue .
reported fdg - pet as a method to assume the pattern of local failure after radiation therapy .
they analyzed the data of 26 patients with 34 recurrent legions that were contoured using a fixed threshold of 42% of the maximum suv by post - rt pet / ct .
the result showed that the pattern of recurrence depended on the radiation dose . at a total dose of < 60  gy ,
at a total dose of 60  gy , recurrences were within the marginal zone of the target volume .   similarly , abramyuk et al
they evaluated whether pet / ct is capable of predicting the location of recurrence in patients with nsclc , especially for determining high - risk area in tumor .
after radiation therapy , 2 patients ' lesions had a complete metabolic response and 8 patients ' lesions showed reduced suv . however , all patients were diagnosed with recurrence 12 months after the radiation therapy .
the location of recurrence was mostly in the most active metabolic lesion ( threshold > 35% of suv max ) of primary tumor .
this result may be applied to further radiation therapy of additional doses to the area of higher fdg uptake .  
elective nodal irradiation to the mediastinal lymph regions in the treatment of stage iii nsclc patients is still a controversy [ 37 , 38 ] .
retrospectively evaluated the failure rates in uninvolved nodal regions with involved - field radiotherapy for inoperable 524 patients with nsclc .
the 2-year elective nodal control rate was 91% and the authors concluded that involved - field radiotherapy did not cause a significant amount of failure in lymph node regions .
rtog0117 also performed involved - field radiotherapy to perform high - dose irradiation without severe side effects .
however , some clinicians have raised the concern that omission of elective nodal irradiation requires a further discussion , because recurrence of lymph nodes is usually fatal and microscopic metastasis of lymph nodes occurs substantially in advanced nsclc .
fdg - pet can contribute to accurate evaluation of nodal lesions , compared with ct alone [ 41 , 42 ] .
conducted a prospective study of involved - field radiotherapy based on fdg - pet for 44 patients . in this study , only 1 patient ( 2.3% ) developed an isolated nodal failure , and the authors concluded that fdg - pet was useful in the involved - field radiotherapy for nsclc patients . furthermore , kolodziejczyk et al .
reported that fdg - pet should be used even in the elective nodal irradiation planning for nsclc , because elective nodal irradiation may not compensate the unsuspected mediastinal lymph nodes .
it is controversial whether elective nodal irradiation can be safely omitted by fdg - pet or not .
however , this strategy is extremely attractive because it allows radiation - dose escalation without severe side effects .
further studies are warranted to establish the utility of fdg - pet in nsclc for radiation planning .
sclc often represents an aggressive clinical course and high incidence of distant metastasis because of rapid tumor growth . despite aggressive treatment ,
although accurate staging is essential for determining the treatment strategy in sclc , it is difficult to evaluate the extension of disease accurately , and especially mediastinum lymph node metastases .
prospectively examined the role of pet / ct compared with standard staging ( ct and bone scintigraphy ) in 29 sclc patients . in their study , pet / ct changed the stage in 5 of the 29 patients ( 17% ) , with the authors concluding that pet / ct improves the accuracy of staging in sclc .
in other studies , 8.3% to 9.5% of limited - disease sclc staged by the conventional staging procedures was upstaged to extended - disease sclc after fdg - pet information was incorporated [ 46 , 47 ] .
arslan et al . evaluated the accuracy and overall survival staged by fdg - pet or ct imaging .
pet scan upstaged 9 ( 36% ) in 25 patients and downstaged 2 ( 8% ) in 25 patients who were staged by ct imaging .
furthermore , fdg - pet staging predicted significant survival difference ( p = 0.019 ) , while ct imaging did not ( p = 0.055 ) .
these studies recommended that fdg - pet should be performed for initial staging in limited - disease sclc patients .   compared with nsclc
, few studies have been performed regarding the delineation based on fdg - pet for sclc .
fdg - pet in sclc patients may improve the delineation of tumor volume as well as nsclc . for limited - disease sclc ,
elective nodal irradiation for mediastinal lymph node regions has been considered necessary to reduce lymph node failure .
however , some clinicians have attempted to avoid elective nodal irradiation because extended radiotherapy volume leads to severe side effects .
conducted a phase ii study of involved - field radiotherapy for limited - disease slcl staged by ct imaging .
also conducted a phase ii trial of involved - field irradiation based on ct imaging for limited - disease sclc .
they evaluated overall survival and isolated nodal failure defined as recurrence in regional nodes outside the target volume in the absence of in - field failure . in their study , isolated mediastinal lymph node recurrence was unexpectedly high ( 11% ) . given these findings , a report from the international atomic energy agency ( iaea ) consultants ' meeting indicated that involved - field irradiation in sclc was controversial and should be performed in a prospective clinical trial .  
currently , fdg - pet is expected to determine whether elective nodal irradiation is necessary or not .
two recent studies have shown the usefulness of fdg - pet in omitting elective nodal irradiation in sclc [ 52 , 53 ] .
van loon et al . conducted a prospective study of involved - field irradiation on the basis of fdg - pet for 60 patients with limited - disease sclc .
median actuarial overall survival was 19 months and isolated nodal failures was low ( 3% ) .
the authors concluded that treatment planning based on fdg - pet could decrease isolated nodal failures , compared with their previous results ( isolated nodal failure : 11% ) treated by ct - based involved - field irradiation .
shirvani et al . reported that involved - field irradiation by intensity - modulated radiotherapy ( imrt ) for 60 patients with limited - disease slcl was staged by fdg - pet . in this study ,
the 2-year actuarial overall survival was 58% and isolated elective node was observed in only one patient ( 3% ) .
these studies concluded that elective nodal irradiation could be safely omitted by fdg - pet staging in sclc .
avoidance of mediastinal lymph nodes that are pet - negative can lead to ( 1 ) a reduction of toxicity with the same radiation dose or ( 2 ) dose escalation with the same toxicity .
although involved - field irradiation based on fdg - pet is an attractive treatment in sclc , there is not enough information to recommend the strategy .
further prospective studies are required to determine whether elective nodal irradiation can be safely omitted by fdg - pet staging in sclc .  
another possible role of fdg - pet in sclc is in the evaluation of the therapeutic response .
a preliminary study showed that fdg - pet could predict the outcome of treatment by radiotherapy or chemotherapy .   in conclusion ,
although the use of fdg - pet in radiation treatment planning for sclc is still controversial , involved - field irradiation based on fdg - pet is an attractive strategy .
fdg - pet - based treatment planning will change the strategy for limited - disease sclc .
in the treatment of esophageal cancer , radiotherapy is commonly used in combination with chemotherapy .
currently , radiotherapy requires accurate target volume definition based on treatment planning by ct scan .
although planning - ct - based target volume definition is considered the gold standard in esophageal cancer , applying fdg - pet to treatment planning may have several advantages , such as accurate staging and delineation of tumor .  
reported that 70 primary tumors of 74 patients were detected by fdg - pet , with a sensitivity of 95% .
the authors showed that fdg - pet had a higher accuracy for stage iv disease compared with conventional modalities ( 82% versus 64% , p = 0.004 ) .
van vliet et al . performed a meta - analysis to evaluate the diagnostic performance of ct and fdg - pet in staging of esophageal cancer .
the sensitivities of ct and fdg - pet for regional lymph node metastases were 0.50 and 0.57 , respectively , and their specificities were 0.83 and 0.85 , respectively .
the authors concluded that each modality plays a distinctive role in the detection of esophageal cancer .
the additional information provided by fdg - pet is expected to improve tumor delineation and accurate staging of lymph nodes and distant metastases .
several studies have investigated the optimal method for delineating the target volume by fdg - pet .
moureau - zabotto et al . evaluated the effect of the addition of fdg - pet to ct in tumor delineation of 34 esophageal cancer patients .
fdg - pet decreased the length of gtv in 12 patients ( 35% ) and increased the length in 12 patients ( 35% ) .  
konski et al . used suv 2.5 to delineate the tumor extension and evaluated the ct - based tumor length in 25 esophageal cancer patients .
the authors concluded that fdg - pet provides additional information for the identification of gtv .
compared fdg - pet - based tumor length with surgical specimens and showed that suv 2.5 seemed closest to the pathological length .
reported that automated interpretation of fdg - pet using mean activity of the liver plus 2 standard deviations likely affect target definition .
compared 11 different methods : suv 2.0 , 2.5 , 3.0 , and 3.5 ; suv max 40% , 45% , and 50% ; mean liver suv plus 1 , 2 , 3 , and 4 standard deviations .
the authors concluded that the use of a threshold of approximately 2.5 was the optimal method for the delineation of gtv in esophageal cancer , regardless of suv thresholding method .  
recent studies indicated that suv 2.5 may be an optimal threshold , but autocontouring using this threshold is not satisfactory .
further investigations are required to utilize fdg - pet in the tumor delineation for esophageal cancer in clinical use .
another method to utilize fdg - pet in treatment planning is to reduce interobserver variability .
evaluated the tumor volumes delineated by fdg - pet in 28 esophageal cancer patients by three radiation oncologists .
the authors concluded that fdg - pet might improve target volume definition with less geographic misses , but the effects on interobserver variability were not significant .
vesprini et al . compared fdg - pet / ct with ct alone for the identification of gtv in 10 patients with esophageal cancer by 6 radiation oncologists .
muijs et al . reported that the additional use of fdg - pet led to the modification of ct - based radiotherapy planning in 57% of esophageal cancer patients .
furthermore , they showed that fdg - pet significantly changed the radiation dose for organs at risk , such as heart and lung .
the additional information provided by fdg - pet has the possibility of improving the local control due to less geographic misses . however , there are no studies that showed whether fdg - pet affects survival or local control rate .
further studies are warranted to establish the role of fdg - pet in highly accurate radiotherapy planning for esophageal cancer .
one of the limitations in the use of pet imaging in radiotherapy planning is the low spatial resolution . generally , the spatial resolution of current pet scanners ( 68  mm ) is inferior to that of modern ct scanners ( 1  mm ) .
furthermore , because pet requires several minutes to perform the imaging , tumor motion due to respiration or cardiac action deteriorates pet images and increases diagnostic errors in thoracic cancers .
in fact , it is one of the major limitations of fdg - pet in several tumor types and has been largely responsible for the slow acceptance of fdg - pet when major treatment decisions are made on the basis of a negative fdg - pet .
sakaguchi et al . reported that gated imaging acquisition improved the quality of fdg - pet imaging in a moving phantom model .
evaluated 48 pulmonary nodules in 43 patients by respiratory - gated pet and ungated method .
gated imaging had higher sensitivity and specificity than the ungated method , especially for smaller lesions located in lower lobes .
these findings suggested that respiratory - gated pet should be performed for patients with thoracic cancers with respiratory motions .
currently , 3-deoxy-3-(18)f - fluorothymidine ( flt ) , a pet imaging marker of proliferation , has been introduced as an alternative to fdg for lung cancer .
yang et al . compared the diagnostic efficacy of flt - pet and fdg - pet in nsclc .
the sensitivities of flt- and fdg - pet for primary tumor were 74% and 94% , respectively .
in contrast , flt - pet showed better specificity and accuracy than fdg - pet for lymph nodes .
although the use of flt - pet is still at an investigational level , further studies are expected to continue to evaluate its efficacy .  
when pet is used for radiotherapy planning , a range of uncertainties related to technical , physical , biological , and analytical factors must be considered .
further investigations are warranted to establish highly accurate radiotherapy based on pet imaging for thoracic cancers .
fdg - pet plays a pivotal role in accurate staging and selection of patients to be treated by radiotherapy .
furthermore , fdg - pet improves radiotherapy volume and enables dose escalation without severe side effects in lung cancer patients .
the main advantage of fdg - pet for esophageal cancer patients is the detection of unrecognized lymph nodes or distal metastases .
while fdg - pet was initially expected to result in more accurate target delineation , its efficacy remains controversial and delineation by fdg - pet should not be practiced in clinical use at this stage .
further studies are required to confirm the advantage of fdg - pet in radiotherapy planning for thoracic cancers .
 radiotherapy plays an important role in the treatment for thoracic cancers . 
 accurate diagnosis is essential to correctly perform curative radiotherapy . 
 tumor delineation is also important to prevent geographic misses in radiotherapy planning . 
 currently , planning is based on computed tomography ( ct ) imaging when radiation oncologists manually contour the tumor , and this practice often induces interobserver variability . 
 f-18 fluorodeoxyglucose positron emission tomography ( fdg - pet ) has been reported to enable accurate staging and detect tumor extension in several thoracic cancers , such as lung cancer and esophageal cancer . 
 fdg - pet imaging has many potential advantages in radiotherapy planning for these cancers , because it can add biological information to conventional anatomical images and decrease the inter - observer variability . 
 fdg - pet improves radiotherapy volume and enables dose escalation without causing severe side effects , especially in lung cancer patients . 
 the main advantage of fdg - pet for esophageal cancer patients is the detection of unrecognized lymph node or distal metastases . 
 however , automatic delineation by fdg - pet is still controversial in these tumors , despite the initial expectations . we will review the role of fdg - pet in radiotherapy for thoracic cancers , including lung cancer and esophageal cancer . 
1. Introduction
2. Non-Small-Cell Lung Cancer (NSCLC)
3. Small-Cell Lung Cancer (SCLC)
4. Esophageal Cancer
5. Prospects of PET Imaging for Thoracic Cancers
6. Summary