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Whole Body Metabolic Tumor Volume and Total Lesion Glycolysis Predict Survival in Patients with Adrenocortical Carcinoma
Kei Satoh, BA1,2, Dhaval Patel, MD1, William Dieckmann, MS3, Naris Nilubol, MD1, and Electron Kebebew, MD, FACS1
1Endocrine Oncology Branch, National Cancer Institute, NIH, Bethesda, MD; 2Icahn School of Medicine at Mount Sinai, New York, NY; 3PET Department, Clinical Center, NIH, Bethesda, MD
ABSTRACT
Background. Adrenocortical carcinoma (ACC) is a rare but lethal malignancy with few reliable prognostic markers. FDG-PET metabolic parameters have been shown to pre- dict survival in several cancers. The objective was to determine if metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) could serve as prognostic markers in patients with ACC.
Methods. A total of 30 patients with ACC prospectively underwent 18F-FDG PET/CT prior to treatment. Whole body MTV, TLG, and SUVmax were measured by a semi- automatic method. A median cutoff was used to determine an association with overall survival (OS) from the time of 18F-FDG PET/CT by the Kaplan-Meier method.
Results. Patients with high whole body MTV (>87.0 mL),TLG (>229.4 SUVIbm*mL), or SUVmax (>8.9 SUV) had a worse OS compared with those with low whole body MTV (median OS, 24 vs 45.1 months, p < . 01), TLG (median OS, 24 vs 40.3 months, p < . 005), or SUVmax (median OS, 23.7 vs 35.5 months, p < . 02). In patients who had operable disease (n = 23), high whole body MTV (>87.0 mL) and TLG (>229.4 SUVIbm*mL) had a worse OS compared with those with low whole body MTV (median OS, 25.1 vs 45.1 months, p < . 05) and TLG (median OS, 25.1 vs 40.3 months, p < . 05), but a high
SUVmax (>8.9 SUV) was not associated with worse OS (p =. 11).
Conclusions. Patients with ACC and a high whole body MTV, TLG, and SUVmax have a worse prognosis and OS. Measurement of whole body MTV and TLG may be helpful for guiding therapy for patients with ACC.
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with an annual incidence of 1-2 cases per million population.1,2 ACC has a bimodal age distribution with a peak in early childhood and in the fourth and fifth decades of life with a slight predominance of women (1.5:1).3-5 Although patients with ACC commonly present with Cushing’s syndrome, ACC is often discovered inci- dentally on imaging or as an enlarging abdominal mass.3,5-8
Consequently, many patients present with late-stage disease, with reports of 25-49 % of patients with stage IV disease at diagnosis.3,9 Despite medical advances in the management of other solid tumors, there has been little change in prognosis for patients with ACC in the past two decades. Overall median survival for resectable and non- resectable disease combined remains at 2 years, while 5-year survival rates range from 66 %, 58-65 %, 24-40 %, to 0-10 % for stage I, II, III, and IV disease, respec- tively.1,10 Surgical resection remains the only curative therapy, improving 5-year survival to 40 %, while treat- ment of surgically unresectable disease is limited to adjuvant mitotane and systemic chemotherapy such as etoposide, cisplatin, and doxorubicin, or streptozocin.” Even with complete surgical resection, up to 80 % of patients will have a recurrence, and there is little evidence to guide management of patients with recurrent disease.9
ACC is a heterogeneous disease with limited tools to help guide patient management. Tumor stage remains the most
K. Satoh and D. Patel have contributed equally.
@ Society of Surgical Oncology 2015 First Received: 10 June 2015
D. Patel, MD e-mail: divot999@gmail.com
reliable and established factor to predict prognosis. 6,13,14 In addition to tumor stage, some studies suggest that tumor size, age, and functionality are associated with survival. 10,15-18 On histopathology, Ki67 index, high mitotic rate, atypical mitotic figures, TP53 mutations, and tumor necrosis have been cited as possible prognostic markers.9,13-15 Addition- ally, gene expression analysis of adrenocortical tumors has identified the expression of genes BUB1B and PINK1 as significant predictors of survival.16 For patients with recur- rent disease, the length of disease-free interval has been shown to be significantly associated with improved survival after surgical resection.17 Reliable prognostic markers are essential in order to inform treatment decisions and improve outcomes for patients with ACC. Prognostic factors may help identify whether patients will benefit from aggressive surgi- cal intervention, adjuvant chemotherapy, or should potentially enroll in clinical trials.
18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is an image modality that provides both anatomical and functional information about tumors. The imaging of tumors is based on the principle that cells with higher glycolytic activity, such as cancer cells, have increased glucose uptake.18 Although the role of 18F-FDG PET/CT in the management of ACC has not been fully elucidated, it has been increasingly used in detection, follow-up, and staging.19-21 Additionally, it has been reported that 18F-FDG PET/CT is highly sensitive (95-100 %) and specific (88-97 %) for the detection of malignant adrenal neoplasms, making it a promising tool in the evaluation of patients with adrenal masses.19,22-27 Pre- vious studies have investigated the prognostic value of maximum standard uptake value (SUVmax) in ACC and found that a SUVmax > 10 was predictive of overall sur- vival.21 Volumetric parameters on 18F-FDG PET/CT such as metabolic tumor volume (MTV) and total lesions glycolysis (TLG), defined as SUVmean multiplied by MTV, have an advantage over single-pixel measurements such as SUVmax, providing a more accurate representation of tumor biology and burden.28 MTV and TLG have been shown to be valu- able prognostic tools in a variety of cancers.29,30
The aim of this study was to determine whether whole body MTV, TLG, and SUVmax as measured on 18F-FDG PET/CT have prognostic value for patients with locally advanced and metastatic ACC and can potentially help guide management strategies.
METHODS
Subjects
A retrospective analysis of a prospective study cohort was performed in 30 patients with ACC evaluated at the
National Institutes of Health (NIH) Warren Magnuson Clinical Center. A total of 23 patients prospectively underwent 18F-FDG PET/CT prior to surgical interven- tion, which was within 1 year of surgery. The remaining seven patients prospectively underwent 18F-FDG PET/CT prior to experimental treatment after undergoing initial surgery and presenting with nonoperable recurrence. Of the patients considered operative candidates, 3 of the 23 patients underwent initial surgery. Of the 23 patients, 20 recurred and underwent reoperative surgery. All patients gave written informed consent, and the study was approved by the institutional review board (IRB).
Imaging
18F-FDG PET/CT scans were performed approximately 60 min after intravenous administration of 10 mCi of 18F- FDG for patients <90 kg and 15 mCi for patients >90 kg. Patients fasted 4-6 h prior to the scan, and blood glucose levels were confirmed to be <200 mg/dL before adminis- tration of the radiotracer. Patients were scanned from the base of the skull to mid-thigh. A low-dose noncontrast CT scan was used for anatomical localization and attenuation correction. Standard uptake values (SUV) were calculated based on the patient’s body weight.
Metabolic Tumor Volume Measurement
Images were analyzed using custom software written in IDL (Excelis Visual Information Solutions, Boulder CO). Tumors were delineated using a semiautomated method with postconstruction smoothing with a Gaussian filter (FWHM, 5 mm) in an operator-defined region of interest (ROI). A threshold of 45 % was used to grow the region outward from the voxel of maximum filtered value within the ROI. Areas of physiologic uptake were excluded. MTV, mean SUVlbm (standardized uptake value lean body mass), and SUV max were measured and recorded for each tumor. TLG was calculated as the product of the mean SUVlbm and MTV for each tumor.
Statistics
The primary outcome measure in the study was overall survival (OS). Whole body MTV and TLG were calculated per patient by summation of all tumors per patient. Various cutoffs were determined of low and high tumor burden. Ultimately, the median was used because of convention and to decrease the likelihood of bias. Median values of whole body MTV and TLG were used to dichotomize patients with high and low tumor burden. OS was defined as months from date of 18F-FDG PET/CT until date of death or date of last follow-up. To analyze whether age was
a predictor of prognosis, OS was defined as months from the date of diagnosis until date of death or date of last follow-up. The Kaplan-Meier method was used to assess the association of whole body MTV, TLG, and SUV max with survival. The statistical difference between Kaplan- Meier curves was determined using log-rank test. Statisti- cal significance was defined as a p value of ≤.05. All calculations were performed using GraphPad Prism (La Jolla, CA).
RESULTS
Clinical data is summarized in Table 1. Of the 30 patients, 19 were female and the average age was 50 years (range 18-70 years). The median follow-up time was 27.3 months (range 12.1-91.1 months). All patients had stage IV disease, and the majority of patients had either local recurrence (20 of 30) or distant metastatic disease at the time of 18F-FDG PET/CT scanning. The number of lesions per disease site, the average MTV by disease site, and the average TLG are summarized in Table 2.
Whole body MTV was measured for each patient (Fig. 1).Patients with high whole body MTV (>87.0 mL), TLG (>229.4 SUVIbm*mL), or SUVmax (> 8.9 SUV) dichotomized based on median cutoff values had a worse OS as calculated from the time of the 18F-FDG PET/CT scan compared with those with low whole body MTV (median OS, 24 vs 45.1 months, p < . 01), TLG (median OS, 24 vs 40.3 months, p < . 005), or SUV max (median OS, 23.7 vs 35.5 months, p < . 02), respectively (Fig. 2a-c). In patients who underwent surgery for operable disease (n = 23), high whole body MTV (>87.0 mL) and TLG (>229.4 SUVIbm*mL) based on a median cutoff value were also associated with a worse OS as calculated from the time of the 18F-FDG PET/CT scan compared with those with low whole body MTV (median OS, 25.1 vs 45.1 months, p < . 05) and low TLG (median OS, 25.1 vs 40.3 months, p < . 05) (Fig. 2d, e). A high SUV max (>8.9 SUV) was not associated with worse OS (p = . 11) (Fig. 2f).Of the 23 surgical patients, 20 patients underwent an operation for recurrent ACC. In an analysis of this subset of recurrent patients, high whole body MTV (>87.0 mL), TLG (>229.4 SUVIbm*mL), or SUVmax (>8.9 SUV) were also associated with a worse OS as calculated from the time of the 18F- FDG PET/CT scan compared with those with low whole body MTV (median OS, 24 vs 26.9 months, p = . 05), TLG (median OS, 24 vs 26.9 months, p < . 05), or SUVmax (median OS, 23.0 vs 26.5 months, p < . 05), respectively.
There was no difference in survival when comparing patients with locoregional disease to patients with distant metastases (median OS, 25.6 vs 25.9 months, p = . 49). Data was also analyzed to assess whether chemotherapy
| Characteristic | Entire cohort |
|---|---|
| No. patients, n (%) | 30 (100) |
| Sex (female/male) | 19/11 |
| Age at diagnosis, mean ± SD | 47.0 ± 13.7 |
| Disease stage, n (%) | |
| IV | 30 (100) |
| Sites of disease | |
| Adrenal, n (%) | 4 (13.3) |
| Local recurrence, n (%) | 23 (76.7) |
| Regional intra-abdominal recurrence, n (%) | 2 (6.7) |
| Lungs, n (%) | 14 (46.7) |
| Liver, n (%) | 8 (26.7) |
| Lymph nodes, n (%) | 1 (3.3) |
| Bone, n (%) | 3 (10.0) |
| Muscle/soft tissue, n (%) | 1 (3.3) |
| Prior treatment | |
| Surgery,ª n (%) | 26 (86.7) |
| Radiotherapy, n (%) | 3 (10.0) |
| Chemotherapy,b n (%) | 26 (86.7) |
| Treatment™ | |
| Initial surgery | 3 (15.0) |
| Reoperative surgery | 20 (66.7) |
| Experimental treatment (nonoperable)d | 7 (23.3) |
| Postsurgical treatmente | |
| Surgery, n (%) | 8 (34.8) |
| Radiotherapy, n (%) | 3 (13.0) |
| Chemotherapy, n (%) | 21 (91.3) |
| MIB1 index of tumor (Ki-67) | >20 % |
a Prior surgeries include primary resection of adrenocortical carci- noma, metastectomy, radiofrequency ablations, and debulking procedures
b Patients received chemotherapeutic regimens including combina- tions of mitotane, etoposide, doxorubicin, cisplatin, protease inhibitors, abraxane, tariquidar, imatinib, streptozocin, or rituximab · Treatment undertaken after 18FDG PET scan
d Presented with nonoperable recurrent tumors after initial resection of primary ACC
e Percentage calculated based on total number of operable patients
compared with no chemotherapy prior to FDG PET/CT scan with operative intervention or experimental treatment impacted survival (median OS, 25.9 vs 34.4 months, p = . 96). There was no difference in OS between patients receiving and not receiving chemotherapy prior to opera- tive intervention (median OS, 26.0 vs 29.1 months, p = . 39). Finally, there was no difference in survival between patients ≥50 years of age compared with those <50 years old (median OS, 71.9 vs 54.1 months, p = . 76).
| Characteristic | Data |
|---|---|
| Average no. tumors per disease location | |
| Abdomen, n (range) | 3.2 (1-21) |
| Thoracic, n (range) | 1.8 (0-11) |
| Bone, n (range) | .9 (0-14) |
| Soft tissue/muscle | .3 (0-9) |
| Average metabolic tumor volume of tumors per disease locationª (mL) | |
| Abdomen, avg (range) | 157.4 (3.7-1877) |
| Thoracic, avg (range) | 19.2 (1.6-194.6) |
| Bone, avg (range) | 42.2 (1.5-93.7) |
| Soft tissue/muscle, avg (range) | 36.8 (36.8) |
| Average total lesion glycolysis of tumors per disease locationª (SUVIbm*mL) | |
| Abdomen, avg (range) | 1478.2 (3.9-28745.1) |
| Thoracic, avg (range) | 106.4 (1.8-1320.2) |
| Bone, avg (range) | 109.4 (3.1-365.0) |
| Soft tissue/muscle, avg (range) | 150.8 (150.8) |
a Averages (avg) taken when quantifiable disease is present and visualized on FDG PET scan
A
B
C
·
FIG. 1 Recurrent left adrenocortical carcinoma and lung metastases (a) that were FDG avid (b). Only the metabolically active portions of the tumor sites were measured (c)
DISCUSSION
In this study, we found high whole body MTV, TLG, and SUVmax is associated with decreased survival in patients with advanced ACC. Furthermore, a subanalysis of patients with resectable disease showed that patients with a high whole body MTV and TLG had a worse prognosis.
These findings suggest that metabolic volumetric parame- ters may be useful to guide management of patients with ACC.
For patients with operable disease, those with high tumor burden had decreased OS as calculated from the time of 18F-FDG PET/CT scan. Interestingly, the majority of operable patients were undergoing an operation for
A
Overall Survival by Whole Body MTV for Entire Cohort
B
Overall Survival by Whole Body TLG for Entire Cohort
C
Overall Survival by SUVmax for Entire Cohort
100
100
- High MTV (n=15)
- High TLG (n=15)
100
- High SUVmax (n=15)
- Low MTV (n=15)
- Low TLG (n=15)
- Low SUVmax (n=15)
80
80
80
Percent survival
Percent survival
Percent survival
60
60
60
40
40
40
20
20
20
0
0
20
40
60
80
100
0
0
20
40
60
80
100
0
0
20
40
60
80
100
OS (months)
OS (months)
OS (months)
D
Overall Survival by Whole Body MTV for Operable Patients
E
Overall Survival by Whole Body TLG for Operable Patients
F
Overall Survival by SUVmax for Operable Patients
100
- High MTV (n=12)
100
- High TLG (n=11)
100
- Low MTV (n=11)
- High SUVmax (n=9)
- Low TLG (n=12)
- Low SUVmax (n=14)
80
80
80
Percent survival
Percent survival
Percent survival
60
60
60
40
40
40
20
20
20
0
0
20
40
60
80
100
0
0
20
40
60
80
100
0
0
20
40
60
80
100
OS (months)
OS (months)
OS (months)
recurrent disease (20 of 23). These patients undergoing reoperative surgery for recurrent disease with high tumor burden had a decreased OS compared with those with low tumor burden. Erdogan and colleagues recently performed a multivariate analysis of patients undergoing surgery for recurrent ACC and found time to first recurrence (>12 months) and resectability of tumor lesions to be the best predictors of survival for patients undergoing an operation for recurrent ACC.31 The majority of the patients in this cohort seen at the NIH presented with distant metastatic disease and recurred greater than 12 months after initial surgery (13 of 18 who underwent an R0 resection at an outside institution). The data presented here shows that there is a subgroup of patients with low whole body MTV, TLG, and SUVmax who would benefit from surgery, which may be unrelated to time to recurrence. Furthermore, this type of study and analysis could poten- tially be applied to a larger cohort and to patients who recur after 12 months to try to select the best operative candi- dates. Those patients, who have a high tumor burden upon recurrence, and poor survival, may benefit from systemic and/or experimental therapy as they are unlikely to benefit from operative intervention.
Operative intervention has been shown to be important in the prognosis and survival of patients with ACC.32,33 Ayala-Ramirez et al. showed in 330 patients that disease- free survival and OS was improved in those patients who
showed survival was significantly different by high whole body MTV (d) and TLG (e). There was no overall difference in overall survival using SUV max as a cutoff (f)
underwent resection of their primary tumor. The authors recommended that patients with metastatic disease at time of presentation undergo chemotherapy or cytoreductive surgery, with possible surgery if the patient were to have a partial response.34 However, in our study, patients with low whole body MTV, TLG, and SUVmax may still derive a significant improvement in OS as calculated from the time of 18F-FDG PET/CT scan regardless of the presence of distant disease. Since the indications for surgery for resection of metastatic disease are not well defined, our type of analysis may help define a way to quantify tumor burden and direct management decisions.33 Additionally, this type of tumor burden analysis could be further applied to follow disease progression or response to treatment.
Clinical stage is the leading prognostic factor for patients with ACC.6,13,14 The 5-year survival for patients with stage IV disease is dismal at 0-10 %.1 In addition, Ki- 67 has been shown to have prognostic value in multiple studies, with higher mitotic index associated with worse survival.13-15 The patients in our cohort all had stage IV disease and a high mitotic index (>20 %). By limiting our cohort to a given clinical stage, our results may have better clinical relevancy and applicability to a subgroup of patients in a disease with highly heterogeneous nature. Patients with advanced ACC pose a therapeutic challenge for providers as guidelines for management are not fully defined. Volumetric parameters may serve as a tool to
further stratify patients with stage IV disease and high mitotic count and contribute to the evaluation and man- agement of these patients.
There are a number of limitations to this study including retrospective analysis, small study cohort, and variable treatment administration. The size of this cohort is small, but given the rarity of ACC, data presented here provides potential avenues for further research in larger cohorts. In addition, these findings can help guide clinicians in making clinical judgments on whether to operate on a patient with high whole body MTV, TLG, and SUVmax or to consider neoadjuvant chemotherapy. Effective systemic therapy continues to be lacking in ACC, and as our analysis showed, systemic chemotherapy had minimal influence on OS.
In conclusion, patients with advanced ACC and a high tumor burden as determined by whole body MTV, TLG, and SUV max have a worse prognosis and OS as calculated from the time of 18F-FDG PET/CT scan. Whole body MTV and TLG may be useful to quantify tumor burden and guide therapy for patients with ACC and in particular, patients who may be considered surgical candidates.
ACKNOWLEDGMENT This research was supported by the intramural research program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health and the National Institutes of Health (NIH) Medical Research Scholars Pro- gram, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable Foundation, The Newport Foundation, The American Association for Dental Research, The Howard Hughes Medical Institute, and the Colgate-Palmolive Company, as well as other private donors. For a complete list, please visit the Foundation website at:http://fnih.org/work/education-training-0/medical- research-scholars-program.
REFERENCES
1. Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A. Extent of disease at presentation and outcome for adrenocortical carci- noma: have we made progress? World J Surg. 2006;30:872-8.
2. Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW. Clinical review: prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab. 2009;94:1853-78.
3. Wooten MD, King DK. Adrenal cortical carcinoma. Epidemiol- ogy and treatment with mitotane and a review of the literature. Cancer. 1993;72:3145-55.
4. Wajchenberg BL, Albergaria Pereira MA, Medonca BB, et al. Adrenocortical carcinoma: clinical and laboratory observations. Cancer. 2000;88:711-36.
5. Koschker AC, Fassnacht M, Hahner S, Weismann D, Allolio B. Adrenocortical carcinoma-improving patient care by establish- ing new structures. Exp Clin Endocrinol Diabetes. 2006;114: 45-51.
6. Luton JP, Cerdas S, Billaud L, et al. Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med. 1990;322:1195-201.
7. Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol. 2003;149:273-85.
8. Barzon L, Boscaro M. Diagnosis and management of adrenal incidentalomas. J Urol. 2000;163:398-407.
9. Fassnacht M, Allolio B. Clinical management of adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab. 2009;23:273-89.
10. Icard P, Goudet P, Charpenay C, et al. Adrenocortical carcino- mas: surgical trends and results of a 253-patient series from the French Association of Endocrine Surgeons Study Group. World J Surg. 2001;25:891-7.
11. Vaughan ED, Jr. Diseases of the adrenal gland. Med Clin North Am. 2004;88:443-66.
12. Tessonnier L, Ansquer C, Bournaud C, et al. (18)F-FDG uptake at initial staging of the adrenocortical cancers: a diagnostic tool but not of prognostic value. World J Surg. 2013;37:107-12.
13. Stojadinovic A, Ghossein RA, Hoos A, et al. Adrenocortical carcinoma: clinical, morphologic, and molecular Characteriza- tion. J Clin Oncol. 2002;20:941-50.
14. Assie G, Antoni G, Tissier F, et al. Prognostic parameters of metastatic adrenocortical carcinoma. J Clin Endocrinol Metab. 2007;92:148-54.
15. Morimoto R, Satoh F, Murakami O, et al. Immunohistochemistry of a proliferation marker Ki67/Mib1 in adrenocortical carcino- mas: Ki67/Mib1 labeling index is a predictor for recurrence of adrenocortical carcinomas. Endocr J. 2008;55:49-55.
16. de Reynies A, Assie G, Rickman DS, et al. Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival. J Clin Oncol. 2009;27:1108-15.
17. Datrice NM, Langan RC, Ripley RT, et al. Operative manage- ment for recurrent and metastatic adrenocortical carcinoma. J Surg Oncol. 2012;105:709-13.
18. Czernin J, Allen-Auerbach M, Nathanson D, Herrmann K. PET/ CT in oncology: current status and perspectives. Curr Radiol Rep. 2013;1:177-90.
19. Deandreis D, Leboulleux S, Caramella C, Schlumberger M, Baudin E. FDG PET in the management of patients with adrenal masses and adrenocortical carcinoma. Horm Cancer. 2011; 2:354-62.
20. Mackie GC, Shulkin BL, Ribeiro RC, et al. Use of [18f]fluo- rodeoxyglucose positron emission tomography in evaluating locally recurrent and metastatic adrenocortical carcinoma. J Clin Endocrinol Metab. 2006;91:2665-71.
21. Leboulleux S, Dromain C, Bonniaud G, et al. Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adrenocortical carcinoma: a prospective compar- ison with computed tomography. J Clin Endocrinol Metab. 2006;91:920-5.
22. Groussin L, Bonardel G, Silvera S, et al. 18f-fluorodeoxyglucose positron emission tomography for the diagnosis of adrenocortical tumors: a prospective study in 77 operated patients. J Clin Endocrinol Metab. 2009;94:1713-22.
23. Boland GW, Dwamena BA, Jagtiani Sangwaiya M, et al. Char- acterization of adrenal masses by using FDG PET: a systematic review and meta-analysis of diagnostic test performance. Radi- ology. 2011;259:117-26.
24. Gust L, Taieb D, Beliard A, et al. Preoperative 18F-FDG uptake is strongly correlated with malignancy, Weiss score, and molecular markers of aggressiveness in adrenal cortical tumors. World J Surg. 2012;36:1406-10.
25. Blake MA, Slattery JM, Kalra MK, Halpern EF, Fischman AJ, Mueller PR, Boland GW. Adrenal lesions: characterization with fused PET/CT image in patients with proved or suspected malignancy-initial experience. Radiology. 2006;238:970-7.
26. Boland GW, Blake MA, Holalkere NS, Hahn PF. PET/CT for the characterization of adrenal masses in patients with cancer: qual- itative versus quantitative accuracy in 150 consecutive patients. Am J Roentgenol. 2009;192:956-62.
PET Parameters Predict Survival in ACC
27. Ganeshan D, Bhosale P, Kundra V. Current update on cytoge- netics, taxonomy, diagnosis, and management of adrenocortical carcinoma: what radiologists should know. AJR. Am J Roent- genol. 2012;199:1283-93.
28. Larson SM, Erdi Y, Akhurst T, et al. Tumor treatment response based on visual and quantitative changes in global tumor gly- colysis using PET-FDG imaging. The visual response score and the change in total lesion glycolysis. Clin Positron Imaging. 1999;2:159-71.
29. Chung HW, Lee KY, Kim HJ, Kim WS, So Y. FDG PET/CT metabolic tumor volume and total lesion glycolysis predict prognosis in patients with advanced lung adenocarcinoma. J Cancer Res Clin Oncol. 2014;140:89-98.
30. Picchio M, Kirienko M, Mapelli P, et al. Predictive value of pre- therapy (18)F-FDG PET/CT for the outcome of (18)F-FDG PET- guided radiotherapy in patients with head and neck cancer. Eur J Nucl Med Mol Imaging. 2014;41:21-31.
31. Erdogan I, Deutschbein T, Jurowich C, et al. The role of surgery in the management of recurrent adrenocortical carcinoma. J Clin Endocrinol Metab. 2013;98:181-91.
32. Kendrick ML, Lloyd R, Erickson L, et al. Adrenocortical carci- noma: surgical progress or status quo? Arch Surg. 2001;136: 543-9.
33. 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. Endocr Relat Cancer. 2005;12:667-80.
34. Ayala-Ramirez M, Jasim S, Feng L, et al. Adrenocortical carci- noma: clinical outcomes and prognosis of 330 patients at a tertiary care center. Eur J Endocrinol. 2013;169:891-9.