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  Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 2  |  Page : 270-273
 

Thymic epithelial tumors: Can fluorodeoxyglucose positron emission tomography help in predicting histologic type and stage?


1 Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
3 Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
4 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
5 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication6-Jan-2017

Correspondence Address:
N C Purandare
Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.197717

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 » Abstract 

Objectives: To study the utility of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting (1) the World Health Organization (WHO) histologic type and differentiating low-risk from high-risk types. (2) Tumor stage and differentiate early from advanced stage disease. Materials and Methods: Patients with thymic epithelial neoplasia who underwent a pretreatment FDG-PET study were included. Tumor maximum standardized uptake value (SUVmax) was correlated with the WHO histologic type and also with the Masaoka-Koga (MK) staging system. Patients with WHO Type A, AB, and B1 were classified as low risk and those with B2 and B3 as high risk. Thymic carcinomas belonged to Type C. Patients with MK Stage I and II disease were grouped as early stage and those with Stage III and IV as an advanced stage. Differences in SUVmax between the various groups were calculated. Results: The SUVmax of thymic carcinomas was significantly higher as compared to low-risk (P = 0.001) and high-risk groups (P = 0.007). The SUVmax of high-risk group was also significantly higher than the low-risk group (P = 0.002). SUVmax cutoff of 6.5 was able to differentiate thymic carcinomas from thymomas with 100% sensitivity and 87.2% specificity. The SUVmax in patients with advanced stage disease showed a higher trend compared to those with early stage, but the difference was not significant (P = 0.167). Conclusion: PET can differentiate thymic carcinomas from rest of the thymoma subtypes by the virtue of their higher FDG uptake. It can also provide valuable information in differentiating high-risk from low-risk thymomas and in predicting disease stage.


Keywords: Neoplasms-primary, positron emission tomography/computerized tomography, thorax, thymus


How to cite this article:
Purandare N C, Pramesh C S, Karimundackal G, Jiwnani S, Agrawal A, Shah S, Agarwal J P, Prabhash K, Noronha V, Joshi A, Kumar R, Rangarajan V. Thymic epithelial tumors: Can fluorodeoxyglucose positron emission tomography help in predicting histologic type and stage?. Indian J Cancer 2016;53:270-3

How to cite this URL:
Purandare N C, Pramesh C S, Karimundackal G, Jiwnani S, Agrawal A, Shah S, Agarwal J P, Prabhash K, Noronha V, Joshi A, Kumar R, Rangarajan V. Thymic epithelial tumors: Can fluorodeoxyglucose positron emission tomography help in predicting histologic type and stage?. Indian J Cancer [serial online] 2016 [cited 2020 Feb 25];53:270-3. Available from: http://www.indianjcancer.com/text.asp?2016/53/2/270/197717



 » Introduction Top


T0068ymic epithelial tumors are the most common primary tumors of the anterior mediastinum in adults.[1] The World Health Organization (WHO) in 2004 revised the classification and divided thymic epithelial tumors into two broad categories: Thymoma which has five subtypes A, AB, B1, B2, and B3 and thymic carcinoma which is also referred as Type C.[2] The WHO classification and the Masaoka-Koga (MK) staging system [3] provide the histological type and stage that act as important prognostic indicators [4],[5] and accurately predicting them is important to plan optimal treatment. Patients with locally advanced disease and high-grade tumors are often advised neo-adjuvant chemotherapy to benefit surgical resection.[6] Morphological imaging using computerized tomography (CT) scanning is limited in its ability to differentiate early stage from advanced stage disease and also low-grade from higher-grade tumors. Fluorine-18 fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET)/CT has been used for diagnosis and staging of various thoracic malignancies and also as a powerful predictive and prognostic tool. The ability of FDG to concentrate to a greater degree in histologically aggressive and higher grades of tumor has led to its use as a surrogate marker of biological behavior of various cancers. The role of FDG-PET/CT in thymic tumors has not yet been clearly defined and only a handful of studies have looked at its ability to predict the stage and differentiate various histological subtypes.

Our primary aim was to study the utility of FDG-PET in predicting the histologic type and differentiating low-risk from high-risk types and also to ascertain if FDG-PET can predict tumor stage and differentiate early from advanced stage disease.


 » Materials and Methods Top


Patient selection

Patients with thymic epithelial neoplasia who underwent a baseline pretreatment FDG-PET/CT study between January 2007 and May 2015 were included in this retrospective analysis. Histopathological confirmation was available in all patients and was obtained by performing either a percutaneous biopsy or surgery. Demographic data of the patients, histopathological reports, and treatment details were obtained from the hospital electronic medical records. Imaging studies were retrieved from the hospital picture archiving and communications system. The study was approved by the Institutional Review Board of our hospital, and a waiver was obtained for the need of informed patient consent.

Tumor classification

WHO classification [2] was determined for each tumor from the operated specimen or the biopsied tissue. According to a simplified histological classification,[7],[8],[9] patients were divided into three groups, those with WHO Type A, AB, and B1 were classified as low risk and those with B2 and B3 as high risk. Thymic carcinomas and carcinoid tumors belonged to WHO Type C. MK staging system [3] was also used in patients where the required staging information was available. Patients with MK Stage I and II disease were grouped as early stage and those with Stage III and IV as an advanced stage.

Data analysis and statistics

The maximum standardized uptake value (SUVmax) of the thymic neoplasms was noted and correlated with the histologic type according to the WHO classification and also with the MK staging system. Mann–Whitney U-test was used to compare the differences in SUVmax between the three groups (low risk, high risk, and thymic carcinoma) and also between the early and advanced stages. A receiver operator characteristic (ROC) curve was used to calculate the SUVmax cutoff for differentiating thymic carcinomas from other thymic epithelial neoplasms.

Fluorodeoxyglucose positron emission tomography/computerized tomography technique

FDG-PET/CT scans were obtained using dedicated FDG-PET/CT scanners (Discovery ST, GE Healthcare, Milwaukee, Wisconsin, USA and Philips Astonish TF, Cleveland, Ohio, USA) incorporating 16 and 64 slice CT components. After checking and confirming the blood glucose levels to be <150 mg/dl, PET/CT studies were performed 60–90 min following intravenous administration of 5 MBq/kg of 18 F-FDG. Scans were obtained from the skull base to the mid-thigh in all patients. Intravenous and oral contrast was administered in all patients unless there was a specific request or clinical indication against it. The SUVmax were automatically generated according to the following equation: SUVmax(bw)= Ctis/Dinj/bw, where SUVmax(bw) is the SUVmax normalized for the body weight, Ctis is tissue concentration expressed as megabecquerels per milliliter, Dinj is injected dose expressed as megabecquerels, and bw is bodyweight expressed as kilograms.


 » Results Top


The study included 52 patients (37 males and 15 females) ranging in age from 16 years to 83 years (median 49 years). The median size of the primary tumor was 7.4 cm (range: 3.1–15 cm). Tumor histology as per the WHO classification was 8 Type A, 6 Type AB, 14 Type B1, 10 Type B2, 1 Type B3, and 13 Type C [Table 1]. Two patients had low-grade neuroendocrine carcinoma (thymic carcinoid). Thirteen patients were diagnosed as MK Stage I, 10 as Stage II, 11 as Stage III, and 10 as Stage IV [Table 2]. Eight Stage IV patients had pleural nodules (Stage IVa), and two patients had the distant metastatic disease (Stage IVb) in abdominal nodes and bone. In eight patients, MK staging was not assigned as their treatment details and follow-up data were not available.
Table 1: Correlation between World Health Organization subtypes and maximum standardized uptake value

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Table 2: Correlation between stage and maximum standardized uptake value

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The SUVmax of tumors according to the WHO classification is shown in [Table 1]. The SUVmax of thymic carcinomas (Type C) was significantly higher as compared to low risk (Types A, AB, and B1), (P = 0.001), and high-risk groups (B2, B3) (P = 0.007), [Figure 1]. The SUVmax of high-risk group was also significantly higher than the low-risk group (P = 0.002), [Figure 1]. Using an ROC curve analysis an SUVmax cutoff of 6.5 was able to differentiate thymic carcinomas from thymomas with a sensitivity of 100% and specificity of 87.2% (area under the curve 0.96). All thymic carcinomas had an SUVmax >6.5. Only five patients with thymomas had an SUVmax >6.5, one with thymoma Type B3, and four with thymoma Type B2. The SUVmax of tumors according to the MK stage is shown in [Table 2]. The SUVmax in patients with advanced stage disease (Stage III and IV) showed a higher trend compared to those with early stage (Stage I and II), but the difference was not significant (P = 0.167), [Figure 2].
Figure 1: Graph showing maximum standardized uptake value of thymic tumors divided into three groups as per the simplified World Health Organization classification. The maximum standardized uptake value of thymic carcinomas (Type C, median 15.2, range: 6.5–24.3) is significantly higher as compared to low-risk (median 4.2, range: 1.2–6.5) (P = 0.001) and high-risk groups (median 6.0, range: 3.9–9.1) (P = 0.007). The maximum standardized uptake value of high-risk group was also significantly higher than the low-risk group (P = 0.002)

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Figure 2: Graph showing maximum standardized uptake value of thymic tumors divided as per Masaoka-Koga stage. The maximum standardized uptake value in patients with advanced stage disease (Stage III and IV) showed a higher trend compared to those with early stage (Stage I and II) but the difference was not significant (P = 0.167)

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Twenty-six patients underwent surgery alone, seven patients received adjuvant chemo/radiation therapy after surgery. Four patients were treated with radical chemoradiation and seven patients with chemotherapy alone. After initial diagnosis and staging PET/CT, treatment details and follow-up data were not available in eight patients.


 » Discussion Top


Thymic carcinomas are more aggressive tumors than thymomas with a much higher propensity for nodal and distant metastases. Thymomas have a much better prognosis than thymic carcinomas.[10] There is evidence to support that neo-adjuvant chemotherapy is effective in patients with locally advanced (Stage III and IV) and biologically aggressive thymomas as well as thymic carcinomas.[11],[12],[13],[14] Thus, knowing the histologic type and stage of thymic epithelial tumors are very important to decide the optimal treatment strategy. In our study, thymic tumors were divided into three groups: Low-risk thymomas (A, AB, and B1), high-risk thymomas (B1 and B2), and thymic carcinomas (Type C). We found that thymic carcinomas [Figure 3] could be differentiated from rest of the thymoma subtypes [Figure 4] on the basis of a significantly higher FDG concentration which was manifested as a statistically significant difference between the SUVmax of the two groups. Likewise, the high-risk thymomas (B2 and B3) also showed a much higher SUVmax as compared to the low-risk group (A, AB, and B1). Our findings are largely similar to a few recently published studies which have used a similar methodology to study FDG uptake in thymic epithelial tumors and thymic carcinomas.[7], 9, [15],[16],[17],[18],[19] Though all the above studies have concluded that it is possible to differentiate thymic carcinomas from high- and low-risk thymomas on the basis of FDG-PET findings, those by Fukumoto et al.[9] and Sung et al.[17] did not find a significant difference in the SUVmax values between the low- and high-risk thymomas. A recent meta-analysis [20] has analyzed the findings of 11 studies and has demonstrated using differences in SUVmax that FDG-PET may be able to predict the WHO grade of malignancy in thymic epithelial tumors. It is unlikely that a universal SUVmax cutoff can ever be defined to differentiate between the different WHO classes of thymic tumors owing to the large overlap of the semi-quantitative values among the different groups across multiple studies.[20] In our study, using an ROC curve analysis we arrived at an SUVmax cutoff −6.5 which was able to differentiate thymic carcinomas from thymomas with a good diagnostic accuracy (sensitivity - 100% and specificity - 87.2%). This value acts as a reasonably good pointer in separating out thymic carcinomas from other thymic tumors as none of the carcinomas had an SUVmax value below this cutoff level.
Figure 3: (a and b) Postcontrast axial computerized tomography scan (a) and fused axial positron emission tomography/computerized tomography (b) in a 42-year-old man show an enhancing thymic tumor (arrows) with intense fluorodeoxyglucose uptake with maximum standardized uptake value 24.3. Histopathology after surgical resection revealed a thymic carcinoma-World Health Organization Type C (high risk) with Masaoka-Koga Stage 3 (advanced stage)

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Figure 4: (a and b) Postcontrast axial computerized tomography scan (a) and fused axial positron emission tomography/computerized tomography (b) in a 67-year-old man show an enhancing thymic tumor (arrows) with low-grade fluorodeoxyglucose uptake with maximum standardized uptake value 4.1. Histopathology after surgical resection revealed the World Health Organization Type A (low risk) thymoma with Masaoka-Koga Stage 2 (early stage)

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The MK staging system which maps the locoregional extent of the disease requires surgical and pathological findings to ascertain capsular and adjacent organ infiltration. Since this information is more anatomical and structural in nature, morphological imaging modalities like CT scan and magnetic resonance imaging have been traditionally used for this purpose. Just a handful of studies have used metabolic findings of FDG-PET to predict the MK stage of thymomas [9],[17],[21],[22] with variable results, some studies reporting a positive correlation between the MK stage and SUVmax. According to a study by Benveniste et al.[18] neither metabolic volume parameters nor SUV (max, mean, and peak) could stratify patients into early and advanced stage. In our study, the SUVmax values showed a higher trend in advanced stage disease (Stage III and IV) [Figure 3] as compared to early stage disease (Stage I and II) [Figure 4] though the difference did not reach statistical significance. Owing to the lack of a positive and significant correlation, the ability of FDG uptake to predict tumor stage appears doubtful.

One of the limitations of our study is its retrospective nature and lack of clinical outcome data. Correlating clinical outcomes with FDG-PET parameters, though a very robust end point, were not the primary objective of our study. As most of the thymic tumors have a long event-free and overall survival, getting meaningful results would have been a lengthy process and not in conjunction with our objective. We have used SUVmax as a semi-quantitative estimate of FDG concentration as it is simple and easy to estimate on all commercially available PET/CT workstations. However, SUVmax values are subject to variations due to various physiological factors such as blood glucose levels and technical factors such as injected activity and reconstruction algorithms and hence it is difficult to arrive at rigid universal cutoff values to differentiate histologies and grades. Calculating ratio of SUVmax of tumor to mediastinum would be one-way of ensuring universality of SUVmax readings.[7],[22],[23],[24],[25] Some researchers have also used in addition to SUVmax other metabolic parameters such as SUVmean and SUVpeak,[18] metabolic tumor volume and total glycolytic volume [26] claiming them to be more reproducible imaging markers. One of the potential drawbacks of our study could be the use of only SUVmax as an estimate of tumor glucose metabolism, though it still remains the most commonly used methodology in most published studies [20] due to its simplicity and ease of computation.


 » Conclusion Top


Higher metabolic activity on FDG-PET can differentiate thymic carcinomas from rest of the thymoma subtypes. It can also provide valuable information in differentiating high-risk from low-risk thymomas. In our study, FDG-PET could not accurately predict disease stage; however, advanced stage disease showed a definite trend toward higher metabolism as compared to early stage disease. Availability of this information in the pretreatment setting can be utilized for the planning of optimal treatment strategies as there is a growing body of evidence to treat locally advanced and aggressive tumors with neo-adjuvant chemotherapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

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Kondo K, Yoshizawa K, Tsuyuguchi M, Kimura S, Sumitomo M, Morita J, et al. WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg 2004;77:1183-8.  Back to cited text no. 4
    
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Igai H, Matsuura N, Tarumi S, Chang SS, Misaki N, Go T, et al. Usefulness of [18F]fluoro-2-deoxy-D-glucose positron emission tomography for predicting the World Health Organization malignancy grade of thymic epithelial tumors. Eur J Cardiothorac Surg 2011;40:143-5.  Back to cited text no. 16
    
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Sung YM, Lee KS, Kim BT, Choi JY, Shim YM, Yi CA. 18F-FDG PET/CT of thymic epithelial tumors: Usefulness for distinguishing and staging tumor subgroups. J Nucl Med 2006;47:1628-34.  Back to cited text no. 17
    
18.
Benveniste MF, Moran CA, Mawlawi O, Fox PS, Swisher SG, Munden RF, et al. FDG PET-CT aids in the preoperative assessment of patients with newly diagnosed thymic epithelial malignancies. J Thorac Oncol 2013;8:502-10.  Back to cited text no. 18
    
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Kaira K, Murakami H, Miura S, Kaira R, Akamatsu H, Kimura M, et al. 18F-FDG uptake on PET helps predict outcome and response after treatment in unresectable thymic epithelial tumors. Ann Nucl Med 2011;25:247-53.  Back to cited text no. 21
    
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Kaira K, Endo M, Abe M, Nakagawa K, Ohde Y, Okumura T, et al. Biologic correlation of 2-[18F]-fluoro-2-deoxy-D-glucose uptake on positron emission tomography in thymic epithelial tumors. J Clin Oncol 2010;28:3746-53.  Back to cited text no. 23
    
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26.
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