18F-FDG PET/CT in the post-operative monitoring of patients with adrenocortical carcinoma

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  • 1 Internal Medicine I, IRMET, Public Health, Pathology, Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Regione Gonzole, 10, 10043 Orbassano, Italy

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Context

The role of 18F-labeled 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the post-operative monitoring of patients with adrenocortical carcinoma (ACC) is still unclear.

Objective

To assess the accuracy of FDG PET/CT to diagnose ACC recurrence in a real world setting.

Design and methods

Retrospective evaluation of data of 57 patients with presumed ACC recurrence at CT scan who underwent FDG PET/CT within a median time of 20 days. We compared the results of either FDG PET/CT or CT with a gold standard confirmation of recurrence (positive histopathology report of removed/biopsied lesions or radiological progression of target lesions at follow-up) to assess their diagnostic performance at different body sites to correctly categorize target lesions. We also assessed whether FDG PET/CT findings may be useful to inform the management strategy.

Results

In 48 patients with confirmed ACC recurrence, we found that FDG PET/CT had lower sensitivity than CT in diagnosing liver and lung recurrences of ACC. FDG PET/CT had higher specificity than CT in categorizing liver lesions. FDG PET/CT had a greater positive likelihood ratio than CT to identify liver and abdominal ACC recurrences. The management strategy was changed based on FDG PET/CT findings in 12 patients (21.1%).

Conclusions

The greater sensitivity of CT may be partly expected due the specific inclusion criteria of the study; however, the greater specificity of FDG PET/CT was particularly useful in ruling out suspected ACC recurrences found by CT. Thus, use of FDG PET/CT as a second-line test in the post-operative surveillance of ACC patients following CT finding of a potential recurrence may have a significant impact on patient management.

Abstract

Context

The role of 18F-labeled 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the post-operative monitoring of patients with adrenocortical carcinoma (ACC) is still unclear.

Objective

To assess the accuracy of FDG PET/CT to diagnose ACC recurrence in a real world setting.

Design and methods

Retrospective evaluation of data of 57 patients with presumed ACC recurrence at CT scan who underwent FDG PET/CT within a median time of 20 days. We compared the results of either FDG PET/CT or CT with a gold standard confirmation of recurrence (positive histopathology report of removed/biopsied lesions or radiological progression of target lesions at follow-up) to assess their diagnostic performance at different body sites to correctly categorize target lesions. We also assessed whether FDG PET/CT findings may be useful to inform the management strategy.

Results

In 48 patients with confirmed ACC recurrence, we found that FDG PET/CT had lower sensitivity than CT in diagnosing liver and lung recurrences of ACC. FDG PET/CT had higher specificity than CT in categorizing liver lesions. FDG PET/CT had a greater positive likelihood ratio than CT to identify liver and abdominal ACC recurrences. The management strategy was changed based on FDG PET/CT findings in 12 patients (21.1%).

Conclusions

The greater sensitivity of CT may be partly expected due the specific inclusion criteria of the study; however, the greater specificity of FDG PET/CT was particularly useful in ruling out suspected ACC recurrences found by CT. Thus, use of FDG PET/CT as a second-line test in the post-operative surveillance of ACC patients following CT finding of a potential recurrence may have a significant impact on patient management.

Introduction

Positron emission tomography (PET) with 18F-labeled 2-fluoro-2-deoxy-d-glucose (FDG) has an established role in the diagnostic approach of different types of tumors (1). More recently, PET/computed tomography (CT), a technique combining the anatomic and densitometric applications of CT and the functional and metabolic advantages of PET, has been increasingly used in oncology (2, 3).

Several studies have reported the effectiveness of FDG PET or PET/CT to differentiate benign from malignant adrenal tumors (4, 5, 6, 7, 8, 9, 10, 11) but only a few studies reported on the use of functional imaging techniques in the follow-up of adrenocortical carcinoma (ACC) (9, 10, 11). Thus, there is limited evidence that PET/CT may refine staging of ACC patients at initial diagnosis or during follow-up. This is not surprising due to the rarity of ACC that hampers progress in the development of management strategies (12, 13).

It could be expected that PET/CT may provide useful and complementary information to CT in the detection of post-operative recurrences. In this clinical scenario, prompt detection of ACC re-growth and a precise definition of disease extension are of the utmost importance because surgery is a mainstay for treatment of ACC recurrence whenever it is done with radical intent (12, 14). However, repeating surgery is often technically demanding and not without risk for the patient while debulking does not offer much benefit (14); thus, an accurate pre-operative estimate of tumor burden is mandatory for the appropriate selection of patients for surgery. However, no recommendation on the use of FDG PET or PET/CT in the follow-up of patients following ACC removal or patients with advanced ACC has been provided in recent reviews (15, 16).

The objective of this work was to assess the accuracy of FDG PET/CT to diagnose ACC recurrence in a real world setting. Owing to the limited availability of the technique and cost issues, we have employed FDG PET/CT as a second-line test in patients with a potential ACC recurrence found by CT during post-surgical follow-up. We have retrospectively correlated FDG PET/CT and CT findings with histopathologic results for patients who underwent surgery or biopsy or radiological progression of target lesions (RECIST criteria) for patients who were not operated on.

Subjects and methods

Patients

Patient data were retrieved from the ACC database of the San Luigi Hospital, a tertiary referral center for patients with adrenal tumors. The database was established in 2001 with the development of a structured data form to collect comprehensive information of all patients with ACC treated at our center. Data of patients before 2011 were collected retrospectively, while in the following years data were input prospectively. Data were retrieved by trained medical personnel using specifically tailored data forms. For the purpose of this study, patients diagnosed between January 1998 and July 2012 were considered and follow-up for this study was closed on December 2013. The Institutional Ethics Committee of our hospital approved the study, and all patients provided written informed consent. Selected patients underwent surgery either at the San Luigi Hospital or at other institutions.

Inclusion criteria for the study were age ≥18, pathologically confirmed diagnosis of ACC (in 50 of 57 cases, diagnosis was made or confirmed by the pathologists of San Luigi Hospital), availability of pre-operative and post-operative CT scans, ACC stages I–III at diagnosis, radical resection of primary tumor, confirmed diagnosis of ACC recurrence during follow-up of a previously tumor-free patient, availability of concomitant FDG PET/CT and complete follow-up information until death or end of the study period. Exclusion criteria were incomplete tumor staging, European Network for the Study of Adrenal Tumors (ENSAT) stage IV ACC, history of other previous/concomitant malignancies, incomplete resection, follow-up of <12 months or incomplete follow-up information, time elapsed between the index CT showing potential ACC recurrence and FDG PET/CT >60 days.

We collected data on patients' demographic and clinical characteristics, their tumor stage at diagnosis, hormonal workup, surgical approach, pathology report, adjuvant mitotane treatment, date and modality of recurrence, and either the date and cause of death or the date of the last follow-up. Staging at diagnosis was based on imaging studies and corroborated by pathological findings at surgery. Staging was reported according to the ENSAT staging system (17). Radical resection was defined as no evidence of microscopic residual disease at pathological analysis. Follow-up visits, which included physical examination, routine laboratory and hormone evaluation, and cross-sectional imaging of the chest and abdomen, were performed every 3–6 months until either disease progression or end of study occurred. For this study, suspected disease recurrence was defined as CT evidence of a possible new tumor site during follow-up (target lesion). The study included only patients with a presumed recurrence (target lesion) found on CT during follow-up.

Imaging techniques

FDG PET images were acquired using the PET Discovery ST (General Electric Medical Systems, Waukesha, WI, USA). Patients were asked to fast for at least 6 h before the exam and a serum glucose level below 160 mg/dl was ensured. Image acquisition was performed after 60 min from i.v. administration of 222–370 MBq of FDG. First an imaging field (CT scout view, with thickness of slices of 3.75 mm) was determined performing a CT scan (140 kV, tube current 80 mA/S) for both anatomical localization and calculation of attenuation correction. Then, PET data were acquired in a three-dimensional mode from the pelvic floor to the skull basis in six to seven bed positions. The acquisition time for PET was 2.5 min/bed position. Coronal, sagittal, and transverse data sets were reconstructed. Co-registered scans were displayed by using dedicated software (Advantage 4.2; GE Healthcare, Buckinghamshire, UK) and integrated FDG PET/CT data sets were prospectively evaluated in consensus by three nuclear medicine physicians. To qualify a PET imaging as positive, we used qualitative visual criteria following the guidelines of the European Association of Nuclear Medicine (18). The rationale is that there is no single lower limit of the intensity of FDG uptake for the detection of abnormal uptake within lesions as it depends on the degree of contrast between the tumor and its immediate surroundings. Thoraco-abdomino-pelvic CT scans were performed after i.v. iodinated contrast with multislice CT whose thickness of slices varied from 0.5 to 1 mm. Images were captured every 3–6 months and were compared to the previous ones with a storage system (Picture Archiving and Communication System (PACS)). Lesions observed with CT and FDG PET/CT were analyzed by location and number, categorizing the findings according to the district (local, abdominal and peritoneal, liver, lung, bone, peritoneal lymph nodes, thoracic lymph nodes, and other districts). Results of CT scans were also evaluated in consensus and compared to the results of FDG PET/CT scans. All evaluations were blinded to the subsequent patient management.

Confirmation of recurrence

The gold standard test for categorizing any target lesion found in a given patient by imaging as ACC recurrence was one of the following: positive histopathology report of removed, or biopsied, lesions and radiological progression according to RECIST criteria of target lesions at follow-up when they were not removed or biopsied.

Statistical analysis

All statistical analyses were performed with Statistica (StatSoft, Tulsa, USA) Statistical Software. Rates and proportions were calculated for categorical data and medians and ranges for continuous data. CT and FDG PET results were compared with the gold standard test by means of 2×2 tables. For FDG PET/CT, we calculated sensitivity (SST=true positive/true positive+false negative), specificity (SPC=true negative/true negative+false positive), positive predictive value (PPV=TP/true positive+false positive), negative predictive value (NPV=true negative/true negative+false negative), positive likelihood ratio (LR+=SST/1−SPC), and negative LR (LR−=1−SST/SPC). The diagnostic accuracy of CT and FDG PET was analyzed by means of the χ2 test and Fisher's exact test. Because the inclusion criteria of the study required positivity of the CT scan (detection of new lesion(s) during follow-up), we did not make a formal comparison of FDG PET/CT vs CT to categorize patients as with or without ACC recurrence. However, we compared the results of either FDG PET/CT or CT with the gold standard confirmation of recurrence to assess their diagnostic performance at different body sites to correctly categorize target lesions as ACC recurrences. We also assessed whether FDG PET/CT findings may be useful to inform the management strategy. P values of <0.05 were considered to indicate statistical significance.

Results

From the overall series of 214 ACC patients who underwent radical resection between 1998 and 2012, four patients were excluded for concomitant malignancies, three were minors at the time of diagnosis, 62 patients did not recur during follow-up, and 33 patients were lost to follow-up. In 57 of 112 patients with presumed ACC recurrence, FDG PET/CT scan was done within a median time of 20 days (range, 3–60 days) from the index CT suggesting disease recurrence and these patients formed the study cohort. Baseline characteristics of the patients are provided in Table 1.

Table 1

Baseline characteristics of the 57 patients.

CharacteristicsValues
Age – median, range42, 18–68
Sex – n, %
 Males25, 43.8%
 Females32, 56.2%
Tumor stage – n, %
 I4, 7.0%
 II33, 57.9%
 III20, 35.1%
Diameter (cm) – median, range10.5, 3.3–30
Weiss score – median, range7, 3–9
Ki-67% – median, range20, 1–70
Secreting tumors – n, %
 Glucocorticoids 18, 31.6%
 Mineralocorticoids3, 5.2%
 Androgens9, 15.8%
 Estradiol1, 1.8%
 Non-secreting/hormonal investigations not available26, 45.6%
Incidentalomas18, 31.6%
Type of surgery – n, %
 Open47, 82.5%
 Laparoscopy10, 17.5%
Adjuvant mitotane – n, %38, 66.6%
Confirmed recurrence – n, %48, 85.9%
RFS (months) – median, range41, 6–105
Treatment of recurrence – n, %
 Surgery21, 36.8%
 Chemotherapy 12, 21.1%
 Radiofrequency ablation5, 8.8%
 Radiotherapy1, 1.8%
 Combination therapies8, 14.0%
 Not treated10, 17.6%

RFS, recurrence-free survival.

In 40 out of 57 patients (70.2%) with one or more new target lesions at CT as a marker of potential ACC recurrence, FDG PET/CT showed at least one significant focal uptake. Assessment of the uptake was performed in a qualitative or quantitative way via the standardized uptake value (SUV). SUV of the target lesions ranged between 1.2 and 15.5, median 6.8. In 48 patients a definitive diagnosis of ACC recurrence was demonstrated by histological analysis of surgically removed lesions (23 cases), fine-needle biopsy (five cases), or detection of radiological progression (RECIST criteria) at imaging follow-up of target lesions (20 cases). In the remaining nine patients, ACC recurrence was not confirmed.

When assessing concordance of CT and FDG PET/CT target lesions with confirmed ACC recurrences, we found that FDG PET/CT had a lower sensitivity than CT in diagnosing liver and lung lesions as ACC recurrences (Tables 2 and 3); however, FDG PET/CT had higher specificity than CT in categorizing liver lesions. FDG PET/CT had a greater LR+ than CT to identify liver and abdominal ACC recurrences. FDG uptake of a liver lesion increases by 38 times the probability of being a true ACC recurrence. FDG uptake of an abdominal lesion increases by 52 times the probability of being a true ACC recurrence (Table 3). A list of false positive findings of PET/CT is given in Table 4.

Table 2

Analysis of pathological lesions detected by CT and FDG PET/CT compared to the gold standard confirmation (histopathology report or radiological evidence of progression). Data are presented per patient.

CTFDG PET/CT
TPFPTNFNTPFPTNFN
Liver1643341003710
Peri-renal space212313192315
Abdomen162345150366
Thorax13438282407
Bone/other6149161491

TP, true positive; FP, false positive; TN, true negative; FN, false negative.

Table 3

Diagnostic accuracy of CT and FDG PET/CT at different sites.

LiverPeri-renal spaceAbdomenThoraxBone and other sites
CTPETCTPETCTPETCTPETCTPET
Sensitivity (SST)0.800.500.870.790.760.700.860.530.860.86
 CI0.58/0.920.30/0.700.69/0.960.60/0.910.55/0.890.50/0.850.62/0.960.30/0.750.49/0.970.49/0.97
Specificity (SPC)0.890.990.940.940.940.990.900.950.980.98
 CI0.75/0.960.89/1.00.80/0.980.80/0.980.82/0.990.88/1.00.78/0.960.84/0.990.90/1.00.90/1.0
PPV0.800.950.910.910.890.970.760.800.860.86
 CI0.58/0.920.68/1.00.73/0.980.71/0.970.67/0.970.76/1.00.53/0.900.49/0.940.49/0.970.49/0.97
NPV0.890.780.910.860.870.850.950.850.980.98
 CI0.75/0.960.65/0.880.77/0.970.71/0.940.73/0.940.71/0.930.84/0.990.72/0.930.90/1.00.90/1.0
LR+7.4038.014.4413.0613.7152.149.1011.242.8642.86
 CI2.9/19.22.3/616.53.7/55.83.4/50.83.5/53.93.3/828.93.5/23.62.7/46.96.0/0.96.0/0.9
LR−0.220.510.130.220.250.300.150.490.150.15
 CI0.09/0.540.33/0.780.05/0.390.10/0.490.12/0.540.16/0.570.04/0.540.28/0.850.03/0.900.03/0.90
Sensitivity, P valueP=0.0467P=0.3504P=0.5000P=0.0543P=0.7692
Specificity, P valueP=0.0574P=0.6934P=0.2465P=0.3379P=0.7525
Table 4

False positive findings of FDG PET/CT scan.

nCT findingsPET/CT findingsConfirmation of status with gold standardGold standard method
1Peri-renal lesionPeri-renal uptakeDisease freeHistology

Imaging F-UP
2Peri-renal lesionPeri-renal uptakeDisease freeHistology

Imaging F-UP
3Peri-renal lesionPeri-renal and thymic uptake Local recurrenceHistology

Imaging F-UP
4Abdominal lesionAbdominal and thymic uptakeAbdominal recurrence Histology

Imaging F-UP
5Liver lesionLiver and colonic uptakeLiver recurrence Histology

Imaging F-UP

F-UP, follow-up. In patient nos 1 and 2, both CT and FDG/PET gave false positive results because the patients were not found to have ACC recurrence at operation. In patient nos 3 and 4, FDG/PET showed thymic uptake that was considered to be physiological. In patient no. 5, FDG/PET showed a colonic uptake that was considered consistent with previous colonoscopy findings of inflammatory bowel disease.

In 26 patients (45.6%), CT and FDG PET/CT findings were superimposable (in two of them, both techniques had false positive results because local recurrence was finally excluded). When analyzing the 31 patients (54.4%) with discordant findings between the two imaging tests, CT showed a greater number of target lesions than FDG PET/CT in 23 patients. Conversely, FDG PET/CT showed additional target lesions not found by CT in four patients. Finally, in four patients FDG PET/CT and CT showed two different target lesions (Fig. 1). In seven of the 23 patients with target lesions at CT without corresponding FDG uptakes, ACC recurrence was excluded (two hepatic nodular hyperplasia, two unspecific pulmonary nodules, two post-surgical scars, and one bone aspecific lesion). In the eight patients with FDG PET/CT target lesions without corresponding CT findings, the additional lesions found by FDG PET/CT were demonstrated to be ACC recurrences.

Figure 1
Figure 1

Discordant results between CT and FDG PET/CT scans: patients with a greater number of target lesions in CT than in FDG PET/CT scans are identified as CT>PET/CT; patients with a greater number of target lesions in FDG PET/CT than CT scans are identified as PET/CT>CT; patients with CT and FDG PET/CT scans showing target lesions in different districts are identified as CT≠PET/CT. Analysis is done per site of lesion.

Citation: European Journal of Endocrinology 173, 6; 10.1530/EJE-15-0707

The management strategy was changed based on PET/CT findings in 12 patients (21.1%) (Table 5). We did not treat eight patients with CT lesions not confirmed by PET. The following workup confirmed no ACC recurrence in seven of them and one patient had to be considered as a false negative of PET/CT. We changed the treatment plan in four out of eight patients who showed FDG PET/CT target lesions without corresponding CT findings. We gave a systemic treatment instead of surgery in one patient and planned a more extensive surgery in three patients, in whom surgical and pathologic reports demonstrated the existence of multiple recurrence sites. In the remaining four patients with discordant findings between techniques, we chose to base management on CT findings, but following investigations demonstrated the presence of ACC recurrence in the sites of FDG uptake.

Table 5

Relevant characteristics of the patients whose management has been changed following FDG PET/CT results.

nCT findingsPET/CT findingsManagement changeStatus at the last visitGold standard methodF-UP since index CT (months)
1One lung lesionNo uptakeF-UP and not surgeryDisease freeImaging F-UP26
2One abdominal lesionNo uptakeF-UP and not surgeryDisease freeImaging F-UP49
3One liver lesionNo uptakeF-UP and not surgeryDisease freeImaging F-UP29
4Three liver lesionsNo uptakeF-UP and not surgeryDisease freeImaging F-UP66
5Two lung lesionsNo uptakeF-UP and not surgeryDisease freeImaging F-UP32
6Two abdominal lesionsNo uptakeF-UP and not surgeryDisease freeImaging F-UP10
7One bone lesionNo uptakeF-UP and not surgeryDisease freeImaging F-UP56
8One liver and one peri-renal lesionNo uptakeF-UP and not surgeryDisease freeHistology

Imaging F-UP
24
9One abdominal lesionMultiple abdominal uptakeChemotherapy and not surgeryDisease progression (multiple sites)Biopsy

Imaging F-UP
8
10One lung lesionOne abdominal uptakeThoraco-abdominal instead of lung surgeryDisease progression (abdomen)Histology

Imaging F-UP
21
11One peri-renal lesionTwo liver and one peri-renal uptakeExtended abdominal surgery instead of liver surgeryDisease progression (liver)Histology

Imaging F-UP
7
12One lung lesionOne peri-renal uptakeThoraco-abdominal surgery instead of abdominal surgeryDisease progression (multiple sites)Histology

Imaging F-UP
10

F-UP, follow-up. Patient no. 8 had an abdominal recurrence at 18 months and was radically operated on.

Discussion

The role of FDG PET/CT in the post-operative monitoring of ACC patients is yet to be established. A single study evaluated the role of FDG PET/CT to diagnose ACC recurrence and showed that PET was more sensitive than CT in detecting local recurrence, while CT was more sensitive in detecting small lung or peritoneal metastases (9). As a consequence, no formal recommendation on incorporating this technique in the surveillance protocol of ACC patients following complete tumor removal has been provided. However, some expert centers add FDG PET/CT at 6-month intervals in the follow-up strategy (16).

In the present study, we have assessed retrospectively our experience at the San Luigi Hospital where FDG PET/CT has been used as a second-line test in patients with a potential ACC recurrence found by CT during post-surgical follow-up. Therefore, we did not make a formal comparison of FDG PET/CT vs CT to categorize patients as with or without ACC recurrence, but we assessed whether the addition of FDG PET/CT in selected cases may refine the diagnosis of ACC recurrence and inform the management strategy. To this aim, we have compared the results of either FDG PET/CT or CT with a gold standard confirmation of recurrence (positive histopathology report of removed/biopsied lesions or radiological progression of target lesions at follow-up) to assess the diagnostic performance of both techniques at different body sites to correctly categorize presumed ACC recurrences.

Sensitivity of CT was overall greater than that of FDG PET/CT, and this may be partly expected due the specific inclusion criteria of the study requiring positivity of the CT scan (detection of new lesion(s) during follow-up). Sensitivity of CT was significantly greater than that of FDG PET/CT in the lungs and liver. The low sensitivity of FDG–PET for lung metastases is already known due to the limited FDG PET/CT resolution of lung nodules <5 mm (9). In our series, many lung metastases were small and frequently located in the inferior lobes, close to the lung bases, where nodules are less detectable due to respiratory movements, compared to nodules in the upper parts of the lung (19).

Specificity of FDG PET/CT was overall greater than that of CT, and the difference was at the limits of statistical significance in the liver. Moreover, FDG PET/CT had a greater LR+ than CT to identify liver and abdominal ACC recurrences. Thus, FDG PET/CT was of particular value in ruling out suspected ACC recurrences found by CT. FDG PET/CT findings informed patient management in 12 cases (21.1%) and the chosen strategy proved to be correct in all but one. In addition, four patients with discordant findings between the two techniques, all sites of pathological uptake by FDG PET/CT without a correspondent anatomical lesion at CT, were finally demonstrated to be true ACC recurrences. Results of FDG PET/CT were not considered to guide management in such patients, but the choice proved to be a mistake.

Strengths of the study are the rather large series considering the rarity of ACC, the central review of radiological material with FDG PET/CT scans done in a single center and the completeness of follow-up with an unequivocal demonstration of recurrence, while we have to disclose the limit of a retrospective analysis and lack of standardization of the time interval elapsed between index CT and FDG PET/CT scan. There are no formal recommendations on the optimal time interval between the two imaging procedures, and in previous work a time interval within 3 months was considered as acceptable (20). However, we should strive to achieve PET within 1 month from CT due to the possibility of fast disease progression. This seems a plausible compromise between the need for the shortest delay possible and the need to face practical problems (i.e., PET availability, travel arrangement for patients living far from the referral center).

Although retrospective assessment of a decision-making process may be partly flawed, the study findings are of clinical relevance showing that the use of FDG PET/CT to confirm anatomical lesions suspected to be ACC recurrences may allow a better selection of patients to surgery. Owing to the limited efficacy of available medical treatments, surgical treatment of ACC recurrences still represents the best option to prolong patient survival whenever surgery can be done with radical intent, and proven that recurrence-free survival from primary surgery be of at least 1 year (21). FDG PET/CT was useful in differentiating liver nodular hyperplasia and post-surgery abdominal inflammatory reactions from ACC recurrence. As a matter of fact, FDG PET/CT pathological uptake of a liver or abdominal lesion increases by 38 or 52 times, respectively, the probability of a target lesion being a true ACC recurrence.

To conclude, we have showed that the use of FDG PET/CT as a second-line test in the post-operative surveillance of ACC patients following CT finding of a potential recurrence may have a significant impact on patient management, in particular for an appropriate selection of patients to surgery. Therefore, we suggest that FDG PET/CT becomes part of the post-operative workup protocol of ACC patients following a CT scan that has identified morphological lesions compatible with ACC recurrences. Despite limited availability of the technique and cost issues, this strategy seems particularly appealing also with the aim of reducing the psychological burden of repeated testing in such patients. It remains to be demonstrated whether the routine use of FDG PET/CT in addition to cross-sectional imaging in the post-operative follow-up of ACC patients may improve detection and, more importantly, treatment of recurrent disease.

Declaration of interest

M Terzolo received research grants and speaker honoraria by HRA Pharma and advisory honoraria by Atterocor. There are no other conflicts of interest to disclose.

Funding

M Terzolo received research grants from the Italian Ministry of University and Scientific Research (grant number FIRB RBAP1153LS_005) and from the University of Turin (grant number TERMATEN 12).

Author contribution statement

A Ardito, E Pelosi, and M Terzolo for study concept and design. A Ardito, B Zaggia, and M Terzolo for patient management. E Pelosi, V Arena, and D Penna for FDG PET scan and analysis and analysis of CT scans. E Duregon for pathological analysis. A Ardito, C Massaglia, and V Basile for data collection and capture. P Perotti for database management and submission to EC. R Brambilla and F Vigna-Taglianti for statistical analysis. C Massaglia for manuscript drafting. All authors for critical input in the manuscript. M Terzolo for final manuscript review.

Acknowledgements

We thank Chiara Sciolla for technical support and the nurse staff of Internal Medicine 1 for dedicated patient's care.

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    Terzolo M, Zaggia B, Allasino B, De Francia S. Practical treatment using mitotane for adrenocortical carcinoma. Current Opinion in Endocrinology, Diabetes, and Obesity 2014 21 159165. (doi:10.1097/MED.0000000000000056).

    • Search Google Scholar
    • Export Citation
  • 14

    Schteingart DE, Doherty GM, Gauger PG, Giordano TJ, Hammer GD, Korobkin M, Worden FP. Management of patients with adrenal cancer: recommendations of an International Consensus Conference. Endocrine-Related Cancer 2005 12 667680. (doi:10.1677/erc.1.01029).

    • Search Google Scholar
    • Export Citation
  • 15

    Berruti A, Baudin E, Gelderblom H, Haak HR, Porpiglia F, Fassnacht M, Pentheroudakis G, ESMO Guidelines Working Group . Adrenal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2012 23 (Supplement 7) vii131vii138.

    • Search Google Scholar
    • Export Citation
  • 16

    Zini L, Porpiglia F, Fassnacht M. Contemporary management of adrenocortical carcinoma. European Urology 2011 60 1055. (doi:10.1016/j.eururo.2011.07.062).

    • Search Google Scholar
    • Export Citation
  • 17

    Fassnacht M, Johanssen S, Quinkler M, Bucsky P, Willenberg HS, Beuschlein F, Terzolo M, Mueller HH, Hahner S, Allolio B et al.. Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a revised TNM classification. Cancer 2009 115 243250. (doi:10.1002/cncr.24030).

    • Search Google Scholar
    • Export Citation
  • 18

    Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, Verzijlbergen FJ, Barrington SF, Pike LC, Weber WA et al.. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. European Journal of Nuclear Medicine and Molecular Imaging 2015 42 328354. (doi:10.1007/s00259-014-2961-x).

    • Search Google Scholar
    • Export Citation
  • 19

    Kim SK, Allen-Auerbach M, Goldin J, Fueger BJ, Dahlbom M, Brown M, Czernin J, Schiepers C. Accuracy of PET/CT in characterization of solitary pulmonary lesions. Journal of Nuclear Medicine 2007 48 214220.

    • Search Google Scholar
    • Export Citation
  • 20

    Pelosi E, Messa C, Sironi S, Picchio M, Landoni C, Bettinardi V. Value of integrated PET/CT for lesion localization in cancer patients: a comparative study. European Journal of Nuclear Medicine and Molecular Imaging 2004 7 932939. (doi:10.1007/s00259-004-1483-3).

    • Search Google Scholar
    • Export Citation
  • 21

    Erdogan I, Deutschbein T, Jurowich C, Kroiss M, Ronchi C, Quinkler M, Waldmann J, Willenberg HS, Beuschlein F, Fottner C et al.. The role of surgery in the management of recurrent adrenocortical carcinoma. Journal of Clinical Endocrinology and Metabolism 2013 98 181191. (doi:10.1210/jc.2012-2559).

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    • Export Citation
*

(A Ardito and C Massaglia contributed equally to this work)

 

     European Society of Endocrinology

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    Discordant results between CT and FDG PET/CT scans: patients with a greater number of target lesions in CT than in FDG PET/CT scans are identified as CT>PET/CT; patients with a greater number of target lesions in FDG PET/CT than CT scans are identified as PET/CT>CT; patients with CT and FDG PET/CT scans showing target lesions in different districts are identified as CT≠PET/CT. Analysis is done per site of lesion.

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    Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology 2004 231 305332. (doi:10.1148/radiol.2312021185).

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    Song JH, Mayo-Smith WW. Current status of imaging for adrenal gland tumors. Surgical Oncology Clinics of North America 2014 23 847861. (doi:10.1016/j.soc.2014.06.002).

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    Deandreis D, Leboulleux S, Caramella C, Schlumberger M, Baudin E. FDG PET in the management of patients with adrenal masses and adrenocortical carcinoma. Hormones & Cancer 2011 2 354362. (doi:10.1007/s12672-011-0091-5).

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    Mackie GC, Shulkin BL, Ribeiro RC, Worden FP, Gauger PG, Mody RJ, Connolly LP, Kunter G, Rodriguez-Galindo C, Wallis JW et al.. Use of [18F]fluorodeoxyglucose positron emission tomography in evaluating locally recurrent and metastatic adrenocortical carcinoma. Journal of Clinical Endocrinology and Metabolism 2006 91 26652671. (doi:10.1210/jc.2005-2612).

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    Leboulleux S, Dromain C, Bonniaud G, Aupérin A, Caillou B, Lumbroso J, Sigal R, Baudin E, Schlumberger M. Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adrenocortical carcinoma: a prospective comparison with computed tomography. Journal of Clinical Endocrinology and Metabolism 2006 91 920925. (doi:10.1210/jc.2005-1540).

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  • 12

    Fassnacht M, Libé R, Kroiss M, Allolio B. Adrenocortical carcinoma: a clinician's update. Nature Reviews. Endocrinology 2011 7 323335. (doi:10.1038/nrendo.2010.235).

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  • 13

    Terzolo M, Zaggia B, Allasino B, De Francia S. Practical treatment using mitotane for adrenocortical carcinoma. Current Opinion in Endocrinology, Diabetes, and Obesity 2014 21 159165. (doi:10.1097/MED.0000000000000056).

    • Search Google Scholar
    • Export Citation
  • 14

    Schteingart DE, Doherty GM, Gauger PG, Giordano TJ, Hammer GD, Korobkin M, Worden FP. Management of patients with adrenal cancer: recommendations of an International Consensus Conference. Endocrine-Related Cancer 2005 12 667680. (doi:10.1677/erc.1.01029).

    • Search Google Scholar
    • Export Citation
  • 15

    Berruti A, Baudin E, Gelderblom H, Haak HR, Porpiglia F, Fassnacht M, Pentheroudakis G, ESMO Guidelines Working Group . Adrenal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2012 23 (Supplement 7) vii131vii138.

    • Search Google Scholar
    • Export Citation
  • 16

    Zini L, Porpiglia F, Fassnacht M. Contemporary management of adrenocortical carcinoma. European Urology 2011 60 1055. (doi:10.1016/j.eururo.2011.07.062).

    • Search Google Scholar
    • Export Citation
  • 17

    Fassnacht M, Johanssen S, Quinkler M, Bucsky P, Willenberg HS, Beuschlein F, Terzolo M, Mueller HH, Hahner S, Allolio B et al.. Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a revised TNM classification. Cancer 2009 115 243250. (doi:10.1002/cncr.24030).

    • Search Google Scholar
    • Export Citation
  • 18

    Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, Verzijlbergen FJ, Barrington SF, Pike LC, Weber WA et al.. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. European Journal of Nuclear Medicine and Molecular Imaging 2015 42 328354. (doi:10.1007/s00259-014-2961-x).

    • Search Google Scholar
    • Export Citation
  • 19

    Kim SK, Allen-Auerbach M, Goldin J, Fueger BJ, Dahlbom M, Brown M, Czernin J, Schiepers C. Accuracy of PET/CT in characterization of solitary pulmonary lesions. Journal of Nuclear Medicine 2007 48 214220.

    • Search Google Scholar
    • Export Citation
  • 20

    Pelosi E, Messa C, Sironi S, Picchio M, Landoni C, Bettinardi V. Value of integrated PET/CT for lesion localization in cancer patients: a comparative study. European Journal of Nuclear Medicine and Molecular Imaging 2004 7 932939. (doi:10.1007/s00259-004-1483-3).

    • Search Google Scholar
    • Export Citation
  • 21

    Erdogan I, Deutschbein T, Jurowich C, Kroiss M, Ronchi C, Quinkler M, Waldmann J, Willenberg HS, Beuschlein F, Fottner C et al.. The role of surgery in the management of recurrent adrenocortical carcinoma. Journal of Clinical Endocrinology and Metabolism 2013 98 181191. (doi:10.1210/jc.2012-2559).

    • Search Google Scholar
    • Export Citation