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European Journal of Radiology 83 (2014) 2224–2230

Contents lists available at ScienceDirect

European Journal of Radiology

j ourna l h o mepage: www.elsev ier .com/ locate /e j rad

8F-FDG PET/contrast enhanced CT in the standard surveillance ofigh risk colorectal cancer patients�

ermán Andrés Jiménez Londonoa,∗, Ana María García Vicentea, Victoria Sánchez Pérezb,átima Jiménez Aragónc, Alberto León Martind, Juana María Cano Canob,sther Domínguez Ferrerasc, Ober Van Gómez Lópeza, Javier Espinosa Arranzb,ngel María Soriano Castrejóna

Department of Nuclear Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real, SpainDepartment of Oncology, Hospital General Universitario de Ciudad Real, Ciudad Real, SpainDepartment of Radiology, Hospital General Universitario de Ciudad Real, Ciudad Real, SpainInvestigation Unit, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

r t i c l e i n f o

rticle history:eceived 21 June 2014eceived in revised form 16 August 2014ccepted 27 August 2014

eywords:olorectal cancerDG PETontrast enhanced CT scanurveillanceecurrence

a b s t r a c t

Objective: To assess the accuracy of FDG-PET/contrast enhanced CT (FDG-PET/ceCT) in the detection ofunsuspected recurrence of colorectal cancer (CRC) in patients with high risk of relapse.Methods: Thirty-three patients (14 females and 19 males, mean age: 62, range: 41–78), with CRC incomplete remission, were prospectively included. All patients underwent FDG-PET/ceCT (58 studies).

FDG-PET/ceCT was requested in the surveillance setting, and performed following a standardizedprotocol. A portal venous phase CT scan was performed after the injection of iodinated contrast agent.

An individual and combined assessment of both techniques (PET and ceCT) was performed. Concordantand discordant findings of PET, ceCT and FDG-PET/ceCT were compared in a patient-based and a lesion-based analysis.

The final diagnosis, recurrence or disease free status (DFS), were established by histopathology orclinical/radiological follow-up of at least 6 months.Results: Seven out of 33 patients had a confirmed recurrence and the rest of patients had a DFS.

In a patient-based analysis the sensitivity and specificity of PET, ceCT and PET/ceCT was of 86% and88%, 86% and 92%, 86% and 85%, respectively.

Attending to the lesion-based analysis, the sensitivity for PET, ceCT and PET/ceCT was of 56%, 71% and97%, respectively.

Both techniques showed a good concordance in the establishment of the final patient status. However,on a lesion-based analysis, no concordance was observed between them.Conclusion: PET and ceCT seem to have similar value in the detection of unsuspected recurrence of CRC ina patient-based analysis. However, the combined assessment of PET/ceCT improves the accuracy in thelesion-based analysis.

. Introduction

In spite of recent advances in treatment, the colorectal cancerCRC) is a major cause of morbidity and mortality throughout theorld, becoming the third most common cancer worldwide and

he fourth most common cause of death [1].

� The results of this study have not been presented neither published before.∗ Corresponding author at: University General Hospital, Nuclear Medicine Depart-ent. C/Obispo Rafael Torija s/n, 13005, Ciudad Real, Spain. Tel.: +0034 926 27800;

ax: +0034 926 27800.E-mail address: gjimenez91@yahoo.com (G.A. Jiménez Londono).

ttp://dx.doi.org/10.1016/j.ejrad.2014.08.016720-048X/© 2014 Elsevier Ireland Ltd. All rights reserved.

© 2014 Elsevier Ireland Ltd. All rights reserved.

The CRC prognosis closely relates to disease stage at initialdiagnosis. The therapeutic approach includes; curative surgicalresection, adjuvant and neoadjuvant therapy for resectable diseaseand chemotherapy for advanced or metastatic colon cancer [2,3].However, despite the accurate treatment, this type of cancer hasa significant rate of relapse. Around 25% to 50% of patients withstage II to III will develop recurrent disease as locoregional recur-rence, distant metastasis, or metachronous colorectal lesions after

5 years of follow-up, with no more than 2 years of median survivaltime after the operation [4].

The early diagnosis, with subsequently treatment of tumorrelapse, seems to be decisive to improve patients’ prognosis. For

Journal of Radiology 83 (2014) 2224–2230 2225

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Table 1Patient’s selection criteria.

Inclusion criteria- Demonstrated active disease of CRC (initial or recurrence) within aperiod of 3 years before the PET/ceCT scan- Stage II-IV of CRC- Curative surgical resection and adjuvant Ch/Rt*

- DFS based on negative (all of them*):- Physical examination- Tumor markers: (CEA <5.5 ng/mL and CA 19.9 <37 UI/ml).- CT, MRI or/and PET/CT

Exclusion criteria- Suspect of recurrence based on a positive (any of them):

- Physical examination- Tumor markers: (CEA ≥5.5 ng/mL and CA 19.9 ≥37 UI/ml)- CT, MRI or/and PET/CT

- Recent surgeries on abdominal and pelvic region (<3 months)- Synchronic tumors- Contraindication for contrast administration (any of them):

- Iodine allergy- Previous treatment with Metformin- Hyperthyroidism- Renal failure

G.A. Jiménez Londono et al. / European

his reason, diverse diagnostic procedures have been developed,ncluding clinical history, physical examination, carcinoembryonicntigen [CEA] monitoring, imaging techniques, and colonoscopy.

Previous authors have revealed that intensive surveillance usingEA and computed tomography (CT) improves timely diagnosis ofecurrence with subsequently improvement of long-term outcome5].

Regarding to contrast enhanced CT (ceCT), the 2005 Update ofn American Society of Clinical Oncology (Practice Guideline) onlyecommends annual CT scan of chest, abdomen, and pelvis for 3–5ears after primary therapy, for patients who are at higher risk ofecurrence and who could be candidates for curative-intent surgery6]. However the optimal radiographic surveillance schedule foratients with CRC undergo curative surgical resection, is still notell determined [7,8].

The clinical position of PET/CT, using the 18F-uorodeoxyglucose (FDG) as a tracer, in the routine managementf CRC varies. According to the National Comprehensive Canceretwork NCCN Guideline [4], PET/CT scanning is not routinely

ndicated both in the staging and in the follow-up of CRC, howevert is indicated in the setting of serial increased CEA and resectable

etastases, in order to identify other localizations and avoidnvasive procedures [9]. Nevertheless, some investigators suggesthat in certain clinical circumstances, like the initial staging ofrimary rectal cancer, FDG PET/CT could change the previoustaging up to 39% of the patients and lead a management changen 18–24% of patients by demonstrating unsuspected metastaticisease or clarifying the nature of indeterminate lesions [10,11].

Nowadays, there is scarcely experience about the application ofET/CT in the surveillance setting. Some authors have investigatedhe roll of FDG-PET in the detection of recurrent disease, findinghe FDG-PET as a valuable adjunct to conventional follow-up inatients with a higher risk of recurrence [12–14]. However, no pre-ious experience has been reported about the combined acquisitionnd interpretation of a FDG-PET/ceCT in the surveillance of CRC.

In the present study, we investigated the usefulness of FDGET/ceCT in the detection of unsuspected recurrent disease inatients with CRC and high risk to relapse.

. Materials and methods

This prospective study was approved by the local Ethics Com-ittee and Investigation Board of our institution. Informed consentas obtained from each patient before the procedure.

.1. Patients

We performed a prospective evaluation of 33 patients withistopathologically proven CRC in complete remission status. Allatients underwent at least a FDG-PET/ceCT between February011 and January 2013, as part of their standard surveillance pro-ocol, in place of conventional ceCT.

All patients met all inclusion criteria and none of the exclusionriteria referred in Table 1. The patients were classified followinghe TNM, according to AJCC cancer staging manual 7th edition [15].

Other information such as tumor grade, TNM stage time fromhe diagnosis to PET/ceCT, previous liver involvement, location ofrimary tumor (colon or rectum-sigma) and disease free time wasollected.

.2. FDG-PET/ce CT study protocol

Patients fasted for at least 4 h before the PET/ceCT examinationnd had blood glucose levels less than 160 mg/dl at the time ofnjection.

Ch/Rt: chemotherapy/radiotherapy; DFS: Disease free status.* Time interval more than 3 months previous to the FDG-PET/ceCT.

PET/ce CT was performed with the same dedicated whole-bodyPET/CT (DSTE 16 s; GE Medical Systems) following a standardizedprotocol.

Data acquisitions were obtained about one hour after the injec-tion of a mean dose of 370 MBq of FDG from the meatus of the earto the mid thigh. Initially a ceCT (120 kV and modulated <440 mA,1.2 mm section thickness) for attenuation correction of PET imageand diagnostic purpose, was performed with the injection of 100 mlof iodinated contrast agent (non ionic Iomeprol) at portal venousphase (60 s delayed).

A whole body emission PET scanner was performed imme-diately after the full-dose CT, covering the identical transversefield of view previously obtained, in three-dimensional (3D) modewith 3 min/bed position. The PET section thickness was 3.8 mm.Iterative reconstruction and scatter correction of images weredone.

2.3. Imaging assessment

Each modality (PET and ceCT) was evaluated independently by 2blinded nuclear medicine physicians and radiologists, respectively,who did not have knowledge of the other imaging results.

Regarding to metabolic images (FDG-PET), a visual analysisof PET findings was done. Any non-physiological focal area ofincreased FDG uptake more than surrounding tissue without regardto size was taken as positive (excluding FDG uptake by benignvariants). Positive findings on FDG PET were localized to anatomicimages from the enhanced CT.

The ceCT images were reported assessing the location, numberand size, of all suspicious of malignancy lesions using radiologi-cal criteria. In general, the suspicious of malignancy was based intemporal criteria (recent appearance) and morphological criteria(nodules, masses or other lesions without typical benign charac-teristics). Specifically and regarding to liver, any hypoenhancinglesion with or without peripheral enhancement with no typicalimaging characteristics of benign lesions and ≥5 mm was classi-fied as malignant. Likewise, a liver lesion was classified as benignif it showed a typically benign enhancement pattern and stabil-ity with respect to studies previous to the cancer diagnosis if

available.

Radiological criteria for lymph nodes were based on size, num-ber, architecture and enhancement. In general, a length higher than8–10 mm of the short axis was adopted to define abnormal size of a

2 Journal of Radiology 83 (2014) 2224–2230

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Table 2Patient characteristics.

Characteristics n

Total patient 33Mean age [range] 62 [41–78]Gender:

Male 19Female 14

Tumor site:Colon 18Rectum-Sigma 15

Tumor gradeI 8II 21III 4

Stage:II 7III 15IV 11

Final diagnosis:DFS 26

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226 G.A. Jiménez Londono et al. / European

ymph node. The pulmonary nodules were radiologically assessedn terms of their size, number, location (upper, middle, or lowerobe), and laterality (right or left lung). The size of a nodule wasefined as the largest diameter measured in axial CT images. Theigns that were used to define a benign pulmonary nodule includedhe lack of temporal change for 2 years or more, and certain benignmaging criteria, including specific patterns of calcification or theresence of fat. Any new bone lesion, lytic or sclerotic, with noypical benign aspects was considered suspicious.

Number and location of suspicious lesions was reported withach technique.

An individual and combined assessment of both techniques (PETnd ceCT) was performed. A lesion was classified as malignanthen considered malignant by either of the two techniques. On

he contrary a lesion was classified as benign if it was consideredenign on both techniques.

.4. Final diagnosis

The final diagnosis of every suspicious lesion for disease recur-ence was established by histopathologic examination, and/orlinical and radiological follow-up for at least 6 months.

Patients were classified as disease free status (DFS) whether noalignant lesion was detected during the follow-up.

.5. Statistical analysis

We compared demographic and clinical variables with the finalvolution (recurrence or DFS), after a minimum follow-up time ofix months, using the Pearson’s chi-squared test.

Concordant and discordant findings of PET, ceCT and PET/ce CTere compared both in patient and lesion-based analysis.

The concordance between the imaging studies and the finaliagnosis according to the status of the lesion or the patient wasssessed with Cohen’s kappa classifying the results in: poor (<0.20),eak (0.21–0.40), moderate (0.41–0.60), good (0.61–0.80) and very

ood (0.81–1.00).Sensitivity (Se), specificity (Sp), positive predictive value (PPV),

egative predictive value (NPV) and accuracy were calculated using standard statistical formula.

All statistical tests were two-sided with a significance level of < 0.05. SPSS 18.0.1 for Windows was used for all analyses.

able 3istribution of suspicious lesions, PET/ceCT findings and final patient status.

Pat Location n PET ceCT

1 Lymph nodes 7 7 2

Liver 2 2 1

Bone 1 1 0

Soft tissue 1 1 0

Lung 3 0 3

2 Lymph node 1 1 1

Lung 5 1 5

3 Lung 4 1 4

4 Lung 4 1 4

5 Liver 1 1 1

Lymph node 1 1 1

6 Liver 1 1 1

7 Mesenterium 1 0 0

8 Colon 1 1 0

9 Colon 1 1 0

10 Mesenterium 1 1 1

11 Presacral 1 0 1

at: patient, n: number of lesions, PET number of lesions detected by PET, ceCT: numberheir combined assessment, DFS: disease free status.

* CT and/or PET/CT were performed at least 6 months after the FDG-PET.

Recurrence 7

n: number of patients, DFS: disease free status.

Regression analysis was performed to determine association offinal patient status (recurrence or DFS) with variables as tumorgrade, time from the diagnosis to PET/ceCT, previous liver involve-ment, location of primary tumor (colon or rectum-sigma), diseasefree time and TNM stage.

3. Results

Fifty-eight PET/ceCT studies belonging to 33 patients were eval-uated. The patient characteristics are summarized in Table 2.

According to the final diagnosis, 7 out of 33 patients had aconfirmed CRC recurrence: 3 by histopathological study and 4 byfollow-up. The rest of patients had a DFS.

3.1. Patients with demonstrated recurrence

In a patient-based analysis, CRC recurrence was detected byPET/ceCT in 6 patients. In all cases, PET/ceCT detected multiplelesions. PET/ceCT failed to detect mesenteric disease in a patient.Table 3 shows the results with more details.

PET/ceCT Final status Validation

7 Recurrence CT,PET/CT*2

1131 Recurrence CT,

PET/CT*54 Recurrence CT, PET/CT*

4 Recurrence CT, PET/CT*

1 Recurrence Biopsy1 Biopsy1 Recurrence Biopsy0 Recurrence PET/CT* and biopsy1 DFS Biopsy1 DFS Biopsy1 DFS Biopsy1 DFS CT, PET/CT*

of lesions detected by ceCT, PET/ceCT: number of lesions detected by PET/ceCT in

G.A. Jiménez Londono et al. / European Journal of Radiology 83 (2014) 2224–2230 2227

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ig. 1. Discordant findings on ceCT and FDG PET of recurrent disease 77-year-old ma) reveal two out of five pulmonary lesions (the other lesions are not showed) corulmonary nodules with mild uptake of FDG (arrowhead). The other lesions were m

In a lesion-basis analysis, a total of 32 suspicious of malignancy

esions were detected. Four lesions were confirmed by histologynd the rest in the follow-up due to a progression or treatmentesponse (Figs. 1 and 2).

ig. 2. Concordant findings on ceCT and FDG PET of recurrent disease. 41-year-old man wn ceCT (a) exists a hipovascular liver lesion in segment III, with high FDG uptake in PET

th a CRC stage III. Previous to PET/ceCT, recurrence was not suspected. ceCT imagesding to metastasis (arrows). The PET and fusion images (b and c) show one of the

by PET.

Among the 32 lesions considered malignant, 18 were detected

on PET, 23 on ceCT and 31 on PET/ceCT. There was only a false nega-tive (FN) lesion for both techniques in correspondence with a malig-nant peritoneal implant in the same patient (confirmed by biopsy).

ith a CRC and liver metastasis. Previous to PET/ceCT, recurrence was not suspected.(b) and PET/ceCT (c) images. This lesion was confirmed as malignant by biopsy.

2228 G.A. Jiménez Londono et al. / European Journal of Radiology 83 (2014) 2224–2230

Fig. 3. Discordant findings on ceCT and FDG PET of recurrence disease. 56-year-old woman, with CRC stage IIIB, underwent curative surgery. Previous to PET/ceCT, recurrencewas not suspected. The ceCT (a) shows a soft tissue mass in the presacral region (arrow). In the PET (b) and PET/ceCT (c) images, the presacral lesion does not show avidityfor FDG. At the clinical follow-up, this lesion was not considered as malignant.

Table 4Statistical diagnostic parameters on a patient bases analysis.

Se (%) Sp (%) PPV (%) NPV (%) Acc (%)

PET 85.7 88.4 66.7 95.8 87.9ceCT 85.7 92.3 75.0 96.0 90.9PET/ceCT 85.7 85 85.7 96.1 93.9

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Table 5Demographic and clinical variables in relation to patients’ final status.

Variable Recurrence DFS p

PatientsAge (year)

Mean ± SD 64 ± 12 61 ± 8 0.32Gender 0.79

Male (%) 31.2 68.8Female (%) 35.7 64.3

Tumor site 0.30Colon (%) 25 75Rectum-Sigma (%) 42.9 57.1

Tumor grade 0.71I (%) 50 50II (%) 27.8 72.2III (%) 50 50

TNM stage 0.60IIA (%) 25 75IIB (%) 50 50IIIA (%) 0 100IIIB (%) 20 80IV (%) 50 50

Liver involvement(*) 0.04Yes (%) 83.3 16.7No (%) 20.8 79.2

Time from diagnosisMean ± SD (months) 33.9 ± 28.3 25.4 ± 13.3 0.02Disease-free timeMean ± SD (months) 18.1 ± 11.2 27.2 ± 19.5 0.12

DFS: disease free status, (*) history of liver metastases previously to reach complete

e: sensitivity, Sp: specificity, PPV: positive predictive value, NPV: negative predic-ive value, Acc: accuracy.

.2. Patients with no demonstrated recurrence

With respect to the false classifications, PET classified 2 patientss false positive (FP) due to positive colon uptake. Both cases wereonfirmed by histology and corresponded to colonic adenomasith no high grade of dysplasia. Other FP was detected only by

eCT corresponding to a presacral mass indicative of metastasis.ttending to the clinical and radiological follow-up and an ulterioregative PET/CT scan, this lesion was not considered as malignantFig. 3).

Only one FP mesenteric lymph node was reported by both PETnd ceCT and it was confirmed by histology.

.3. Statistical results

Results of statistical diagnostic parameters on a patient-basisnalysis are showed in Table 4.

In a patient-bases analysis there was a good concordanceetween PET and ceCT (Cohen’s kappa: 0.76; p < 0.05).

Attending to the lesion-bases analysis, the sensitivity for PET,eCT and PET/ce CT was of 56%, 71% and 97%, respectively. However,n a lesion-bases analysis, no concordance between PET and ceCTas observed (Cohen’s kappa: −0.44; p < 0.05).

Statistically significant relations were observed between theocation of malignant lesions and PET and ceCT results, being theET more effective in the detection of small but pathologic lymphodes, liver and bone metastasis (Chi:20, p < 0.05) and the ceCTore accurate in the detection of lung metastasis (Chi:17, p < 0.05).The regression analysis showed no significant relation between

he gender or patient’s age, tumor grade and the percentage ofecurrence or DFS. Recurrence was more frequently diagnosed inatients with primary tumor located in rectum-sigma with respecto whose located in colon (p = 0.30). Advanced TNM stages (III–IV)uffered from recurrence in a higher percentage compared to IItages (p = 0.60). A significant relation was observed between theroups of patients with previous liver involvement, who showed3% of recurrence compared with patients without liver involve-ent (20.8%). All the results are showed in Table 5.

. Discussion

The 5 year survival rate in patients with early CRC is 90%; 70%or disease with regional invasion; and 10% for patients diagnosed

remission.

for metastatic disease [2]. On the other hand, there is a high rate ofrecurrence after surgical treatment of CRC (25% to 50% of patients)and the most deaths are related to distant relapse [4]. Therefore, themain objective of the follow-up must be the recurrence detectionas early as possible, in order to determine those patients who mightbenefit from re-operation or adjuvant therapy.

The follow-up panel recommendations depend on the patternsof recurrent disease. CRC typically recurs in the first 2 years aftercurative surgery and rarely after 5 years, so it is recommendedcomprehensive monitoring in the first 5 years from the diagnosis,although there is no a standardized surveillance schedule [7,8].

Nowadays, intensive surveillance is performed with programsusing tumor markers (CEA, CA 19-9) and imaging techniques suchas CT, chest radiography, ultrasound and MRI, although CT scanningis the most common imaging technique used to follow-up patientswith CRC.

Regarding follow-up, intensive postoperative surveillance aimsto detect asymptomatic recurrences with a potentially curativeresection approach [16,17]. On the other hand, other authorshave reported no differences of recurrence and mortality ratesin patients followed by an intensive follow-up program with CT,

colonoscopy and chest radiography compared to tracking based onsymptoms or by other simple exploratory procedures [5].

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Some studies have revealed the benefit of PET in the detectionf recurrence in the follow-up of CRC patients with reported rangesf sensitivity and specificity of 92–100% and 62–96%, respectively12–14,18–23]. However, most of these studies were performedn patients with suspected recurrence based on inconclusive con-entional tests or abnormal CEA levels, regardless of the abnormalEA value [18–20,22,23]. Furthermore, FDG-PET/CT can accuratelyetect tumor recurrence even in patients, with normal CEA levels20].

Only two groups have used intravenous contrast for the CT com-onent of the PET/CT scan [22,23]. These studies concluded that

ntegrated PET/ceCT revealed additional information comparedith ceCT and standard PET/CT performed separately. Soyka et al.

22] demonstrated, in a group of 54 patients referred for restag-ng, that PET/CT delivered correct additional information to theeCT findings in 27 patients (50%) and PET/ceCT revealed additionalnformation in 39 patients (72%), with therapeutic relevance in 23atients compared with PET/CT. Kitajima et al. [23] demonstrated

n patients for suspected recurrence, that the findings of PET/ceCTad an effect on patient management, 12 patients diagnosed byeCT and 4 patients diagnosed by PET. In our series, we found thathe PET, ceCT and PET/ceCT had similar value in the detection ofnsuspected recurrence of CRC in the patient-based analysis, with alightly higher specificity for the combined assessment of PET/ceCTompared to the isolated evaluation of each technique.

The experience about the use of FDG PET in the standard surveil-ance schedule is limited. In a previous study of 31 asymptomaticatients after curative surgery with normal CEA blood levels, CT andRI, FDG-PET was able to demonstrate recurrence in 5 patients

12]. Sobhani et al. [13] evaluated 130 patients with stage III orV of CRC after curative therapy. The patients were randomizedo undergo either conventional diagnostics procedures (controlroup) or FDG-PET during follow-up. FDG-PET group resulted in

higher number of curative surgical interventions probably due tohe earlier detection of recurrence (12 months in the PET group vs5 months in the control group; p = 0.01), but without differences

n the number of patients with a detected recurrence between thewo groups (23 in the PET group and 21 the control group; p = 0.60).

The rate of curative resection was very limited in our series dueo the multiple metastases detected, contrary to previous reportedorks [12,13].

We found values of Se and Sp in the detection of recurrent dis-ase in asymptomatic patients similar to previous works, who havesed samples of patients with suspicious of recurrence [21,22].owever limitations in detecting microscopic disease and small-

ized lesions exist, with independence of the pre-test probabilityf malignancy [14,22–24].

The detection of active disease in peritoneal lymph nodes is ahallenge for any diagnostic imaging technique. In our work, bothET and ceCT failed in the detection of active disease in mesen-erium. This limitation has been described by other authors [12]. Onhe other hand a false positive in the mesenterium due to inflam-

ation, was found with both techniques.Regarding to the analysis of positive lesions, both PET and ceCT

etected different number and location of lesions, with a higherensitivity for the CT with respect to the PET (71% vs 56%, respec-ively).

On the other hand, our most important finding was the differentistribution of the positive results for both techniques, emphasiz-

ng that the PET had a low rate of detection of lung metastasesompared to ceCT, attributable to the limited spatial resolution andolume partial effect (more of them with diameter <1 cm). Never-

heless, PET detected more nodal involvement than ceCT (lymphodes smaller than 1 cm). Kitajima et al. [23] also demonstratedhat the PET/ceCT showed better sensitivity and accuracy for detec-ion of metastatic lymph nodes than ceCT alone. Because of the

al of Radiology 83 (2014) 2224–2230 2229

identification of metastatic lymph nodules by ceCT is based on mea-surement of node size, the sensitivity of this technique is relativelylow. These findings support the fact that both tests are complemen-tary and recommendable in the routine follow-up protocol of highrisk CRC.

With respect to liver involvement and considering to the liver asthe most frequent visceral localization, CT has shown good in localextension similar to those of FDG-PET [25]. A recent meta-analysisconfirm that 18F-FDG PET/CT is more sensitive than other diagnos-tic techniques for the detection of colorectal liver metastasis at theinitial diagnosis as well as detection of recurrence after hepatec-tomy [26]. However, other studies have shown that the sensitivityof FDG-PET, on a per lesion basis is limited, especially in smalllesions and previous use of neoadjuvant chemotherapy treatment[27,28]. For these reasons, some authors have suggested the utilityof dual time-point PET/CT images in the diagnosis of liver metasta-sis [29]. In the present study four liver metastasis were diagnosed,all of them correctly identified by PET and three by ceCT (Fig. 2).

Although we considered FDG uptake in colonic adenoma as afalse positive result, there are some reports about the increasedrisk of developing colorectal cancer in individuals with a historyof adenomas, especially, in patients with genetic risk factors, andincreased likelihood of future development of metachronous can-cer elsewhere in the colon and rectum [30]. For this reason, thedetection and removal of an adenoma, prior to malignant transfor-mation, may reduce the risk of colorectal cancer [31].

Regarding the false positives, most patients with rectal cancerdevelop a fibrotic mass in the presacral space following surgeryand/or radiotherapy. In this setting, FDG PET/CT has demonstratedhigh sensitivity and specificity (100% and 96%, respectively) for dis-tinguishing between benign and malignant presacral abnormalitieswith an impact on clinical management in 47% of patients [21,24].In our series, a presacral false positive was detected by ceCT andwas correctly evaluated as negative by PET.

In a patient-based analysis, the overall diagnostic accuracy ofPET, ceCT, and PET/ceCT was good for all the techniques (88%, 91%and 85%, respectively). On the contrary, in the analysis per-lesion,the accuracy in the detection of recurrent disease was greater withthe combined evaluation of FDG-PET and ceCT comparing with theisolated assessment of each technique [23,24].

About the limitations, the reduced sample of patients andthe limited number of histological confirmations could affect ourresults although the careful follow-up should overcome latter.

In the standard follow-up of colorectal cancer patients, to thebest of our knowledge, no previous work has reported their expe-rience in the combined assessment of PET and ceCT obtained froman integrated acquisition protocol. Our findings suggest the impor-tance of FDG-PET/ceCT in the detection of regional and distantrelapse in asymptomatic patients with high risk of recurrence.

5. Conclusion

The integrated use of FDG PET/ceCT seems to play an importantrole in the multidisciplinary surveillance and recurrence diagnosisof asymtomatic CRC patients, improving the detection of malignantlesions.

Conflict of interest statement

The authors declare no conflict of interest.

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