High-risk Thymomas Research Articles

Histogram analysis of apparent diffusion coefficient maps for assessing thymic epithelial tumours: correlation with world health organization classification and clinical staging.

To investigate the value of apparent diffusion coefficients (ADCs) histogram analysis for assessing World Health Organization (WHO) pathological classification and Masaoka clinical stages of thymic epithelial tumours. 37 patients with histologically confirmed thymic epithelial tumours were enrolled. ADC measurements were performed using hot-spot ROI (ADCHS-ROI) and histogram-based approach. ADC histogram parameters included mean ADC (ADCmean), median ADC (ADCmedian), 10 and 90 percentile of ADC (ADC10 and ADC90), kurtosis and skewness. One-way ANOVA, independent-sample t-test, and receiver operating characteristic were used for statistical analyses. There were significant differences in ADCmean, ADCmedian, ADC10, ADC90 and ADCHS-ROI among low-risk thymoma (type A, AB, B1; n = 14), high-risk thymoma (type B2, B3; n = 9) and thymic carcinoma (type C, n = 14) groups (all p-values <0.05), while no significant difference in skewness (p = 0.181) and kurtosis (p = 0.088). ADC10 showed best differentiating ability (cut-off value, ≤0.689 × 10-3 mm2 s-1; AUC, 0.957; sensitivity, 95.65%; specificity, 92.86%) for discriminating low-risk thymoma from high-risk thymoma and thymic carcinoma. Advanced Masaoka stages (Stage III and IV; n = 24) tumours showed significant lower ADC parameters and higher kurtosis than early Masaoka stage (Stage I and II; n = 13) tumours (all p-values <0.05), while no significant difference on skewness (p = 0.063). ADC10 showed best differentiating ability (cut-off value, ≤0.689 × 10-3 mm2 s-1; AUC, 0.913; sensitivity, 91.30%; specificity, 85.71%) for discriminating advanced and early Masaoka stage epithelial tumours. ADC histogram analysis may assist in assessing the WHO pathological classification and Masaoka clinical stages of thymic epithelial tumours. Advances in knowledge: 1. ADC histogram analysis could help to assess WHO pathological classification of thymic epithelial tumours. 2. ADC histogram analysis could help to evaluate Masaoka clinical stages of thymic epithelial tumours. 3. ADC10 might be a promising imaging biomarker for assessing and characterizing thymic epithelial tumours.

Can 18F-FDG PET predict the grade of malignancy in thymic epithelial tumors? An evaluation of only resected tumors.

ObjectiveAlthough 18-fluorine fluorodeoxyglucose positron emission tomography (18F-FDG PET) is thought to be useful for predicting the histological grade of thymic epithelial tumors (TETs), it remains controversial. To date, just a few of many previous studies have included only resected cases. Therefore, we investigated 18F-FDG PET findings only in patients with resected TETs.Patients and methodsA total of 112 patients with TETs consisting of 92 thymomas and 20 thymic carcinomas (TCs), resected at two institutes (Shizuoka Cancer Center [Shizuoka] and National Cancer Center Hospital [Tokyo]) between October 2002 and December 2015, were evaluated. Spearman rank correlation coefficient was used to assess the association between the maximum standardized uptake value (SUVmax) in the tumor and both the histological subtype and tumor stage. The cutoff value of SUVmax for differentiating thymoma from TC was calculated.ResultsThe SUVmax was strongly related to both the World Health Organization (WHO) histological subtype and tumor stage based on the eighth edition of the tumor-node-metastasis (TNM) classification (Spearman rank correlation coefficient =0.485 and 0.432; p = 0.000 and 0.000, respectively). There was a significant difference between thymoma and TC. The optimal SUVmax cutoff value for differentiating thymoma from TC was 4.58 (sensitivity: 80% and specificity: 78.3%). In contrast, there was no significant difference between low-risk (type A, AB, and B1) and high-risk (type B2 and B3) thymoma, or between type B3 thymoma and the other subtypes.ConclusionOur results suggest that 18F-FDG PET is useful for differentiating thymoma from TC, but not for predicting the histologic grade of thymoma.

Intravoxel incoherent motion diffusion-weighted MR imaging parameters predict pathological classification in thymic epithelial tumors.

We evaluated the performance of intravoxel incoherent motion (IVIM) parameters for preoperatively predicting the subtype and Masaoka stage of thymic epithelial tumors (TETs). Seventy-seven patients with pathologically confirmed TETs underwent a diffusion weighted imaging (DWI) sequence with 9 b values. Differences in the slow diffusion coefficient (D), fast perfusion coefficient (D), and perfusion fraction (f) IVIM parameters, as well as the multi b-value fitted apparent diffusion coefficient (ADCmb), were compared among patients with low-risk (LRT) and high-risk thymomas (HRT) and thymic carcinomas (TC), and between early stage (stages I and II) and advanced stage (stages III and IV) TET patients. ADCmb, D, and D values were higher in the LRT group than in the HRT or TC group, but did not differ between the HRT and TC groups. The mean ADCmb, D, and D values were higher in the early stage TETs group than the advanced stage TETs group. The f values did not differ among the groups. These results suggest that IVIM DWI could be used to preoperatively predict subtype and Masaoka stage in TET patients.

Doubling time of thymic epithelial tumours on CT: correlation with histological subtype.

We retrospectively evaluated the doubling time (DT) of thymic epithelial tumours (TET) according to the histological subtype on CT. From January 2005 to June 2016, we enrolled 53 patients who had pathologically confirmed TET and at least two CT scans. Tumour size was measured using a two-dimensional method, and the DT was calculated. DTs were compared among histological subtypes, and factors associated with rapid tumour growth (DT <180 days) were assessed. In 42 of the 53 patients (79.2%) the tumours showed interval growth (>2 mm) during follow-up. The median DT for all tumours was 400 days (range 48-1,964 days). There were no significant differences in DT in relation to histological subtype (p = 0.177). When TETs were recategorized into three groups, i.e. low-risk thymomas (types A, AB, B1), high-risk thymomas (types B2, B3), and thymic carcinoma, DT was significantly different among the groups (median DT 436, 381 and 189 days, respectively; p = 0.031). Histological subtype (type B3 and thymic carcinoma) was the single independent predictor of rapid tumour growth. The majority of TETs grew during follow-up with variable and relatively slow growth rates. Histological features of aggressive behaviour significantly correlated with a decreased DT and rapid growth. • The majority of thymic epithelial tumours grew during follow-up (79.2%, 42/53). • Doubling times of thymic epithelial tumours were highly variable (median 400 days). • Histological features of aggressive behaviour significantly correlated with a decreased doubling time.

CT and MRI findings of thymic carcinoid.

To evaluate the CT and MRI findings of thymic carcinoid and to compare these findings with previously published findings of thymoma. 11 cases of pathologically proven thymic carcinoid were reviewed retrospectively. Three patients had typical carcinoid, and eight patients had atypical carcinoid. The characteristics of the tumours and related thoracic abnormalities were assessed in each case on CT and/or MRI by two chest radiologists. The final decisions on the findings were reached by consensus. Thymic carcinoids were more likely to have a large mass (ranging from 18 to 105 mm), irregular contours (n = 8), heterogeneous intensity on T2 weighted images (n = 6; eight patients underwent MRI), heterogeneous enhancement (n = 9) and local invasion (n = 7). A necrotic or cystic component was identified in seven patients (one typical carcinoid and six atypical carcinoids). Lymphadenopathy was seen in four patients. Septum, capsule, haemorrhage and calcification were seen in three patients, two patients, two patients and one patient, respectively, with atypical carcinoid. Thymic carcinoids tend to have a high prevalence of large masses, irregular contours, heterogeneous intensity on T2 weighted images, heterogeneous enhancement and local invasion on CT and/or MRI. A necrotic or cystic component is often seen in atypical carcinoid. Advances in knowledge: Radiologic features of thymic carcinoid mimic those of high-risk thymomas and/or thymic carcinomas.

Correlation of features of chest computed tomographic scans with histologic subtypes of thymoma according to the World Health Organisation classification in asymptomatic patients

Objective To assess the computed tomographic (CT) features of various subtypes of thymic epithelial neoplasms on the basis of the World Health Organization (WHO) classification especially in asymptomatic patients, and provide reference for the clinical treatment strategy of asymptomatic patients with thymoma. Methods We reviewed preoperative CT imaging and postoperative pathological results for 61 thymoma patients who had undergone thymectomy, and assessed the differences in CT features between the low-risk thymoma (type A, B) and the high-risk thymoma (type B1, B2, B3 and C). Results There were no significant differences between low-risk thymoma and high-risk thymoma in the gender (P=0.884), age (P=0.579), maximum diameter (P=0.851), mean diameter(P=0.904) or shape of tumor(P=0.437). However, there were significant differences between the two groups of thymoma in the average CT value on contrast-enhanced images (P=0.001), boundary (P=0.000), homogeneity (P=0.029), calcification (P=0.019), cystic degeneration or necrosis (P=0.000) and involvement of adjacent tissues (P=0.000). The receiver operating characteristic (ROC) curve analysis revealed an average CT value of 68.31 HU on contrast-enhanced images could produce 73.5% sensitivity and 77.8% specificity in determining low risk subtypes, and the area under the curve was 0.76 when the CT value reached this best cutoff point. Conclusion Some features of CT have a certain value in distinguishing low-risk thymoma and high-risk thymoma. A combined prediction using these variables will provide a reference for appropriate therapeutic strategies of TETs patients, especially the asymptomatic ones. Key words: Thymoma; CT imaging feature; World Health Organisation classification

Assessment of Mediastinal Tumors Using SUVmax and Volumetric Parameters on FDG-PET/CT.

Objective(s):This study aimed to evaluate the role of pretreatment SUVmax and volumetric FDG positron emission tomography (PET) parameters in the differentiation between benign and malignant mediastinal tumors. In addition, we investigated whether pretreatment SUVmax and volumetric FDG-PET parameters could distinguish thymomas from thymic carcinomas, and low-risk from high-risk thymomas.Methods:This study was conducted on 52 patients with mediastinal tumors undergoing FDG-PET/CT. Histological examination indicated that 29 mediastinal tumors were benign, and 23 cases were malignant. To obtain quantitative PET/CT parameters, we determined the maximum standardized uptake value (SUVmax), volumetric parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors using SUVmax cut-off value of 2.5. SUVmax, MTV and TLG of benign and malignant tumors were compared using the Mann-Whitney U test. Moreover, receiver-operating curve (ROC) analysis was applied to identify the cut-off values of SUVmax, MTV and TLG for the accurate differentiation of benign and malignant tumors. SUVmax, MTV and TLG were compared between thymomas and thymic carcinomas, as well as low-risk and high-risk thymomas.Results:Mean SUVmax, MTV and TLG of malignant mediastinal tumors were significantly higher compared to benign tumors (P<0.001). Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of SUVmax were 78.2%, 86.2%, 82.6%, 81.8%, and 83.3%, respectively. These values were estimated at 82.6%, 96.6%, 90.4%, 95%, and 87.5% for MTV and TLG, respectively. Additionally, optimal cut-off values for the differentiation of benign and malignant mediastinal tumors were determined at 4.2 and 22.3 mL and 79.7 g for SUVmax, MTV and TLG, respectively. Mean SUVmax, MTV and TLG of thymic carcinomas were significantly higher compared to thymomas (P<0.01), while no significant differences were observed in the mean quantitative parameters between low-risk and high-risk thymomas.Conclusion:Although SUVmax, MTV and TLG could not distinguish between low-risk and high-risk thymomas, these parameters might be able to differentiate benign tumors from malignant mediastinal tumors noninvasively. These parameters could be used to distinguish between thymomas and thymic carcinomas as well. Therefore, FDG-PET/CT parameters seem to be accurate indices for the detection of malignant mediastinal tumors.

Volume-based quantification using dual-energy computed tomography in the differentiation of thymic epithelial tumours: an initial experience.

To investigate the diagnostic value of dual-energy computed tomography (DECT) in differentiating between low- and high-risk thymomas and thymic carcinomas. Our institutional review board approved this study, and patients provided informed consent. We prospectively enrolled 37 patients (20 males, mean age: 55.6years) with thymic epithelial tumour. All patients underwent DECT. For quantitative analysis, two reviewers measured the following tumour parameters: CT attenuation value in contrast Hounsfield units (CHU), iodine-related HU and iodine concentration (mg/ml). Pathological results confirmed the final diagnosis. Of the 37 thymic tumours, 23 (62.2%) were low-risk thymomas, five (13.5%) were high-risk thymomas and nine (24.3%) were thymic carcinomas. According to quantitative analysis, iodine-related HU and iodine concentration were significantly different among low-risk thymomas, high-risk thymomas and thymic carcinomas (median: 29.78 HU vs. 14.55 HU vs. 19.95 HU, p = 0.001 and 1.92mg/ml vs. 0.99mg/ml vs. 1.18mg/ml, p < 0.001, respectively). DECT using a quantitative analytical method based on iodine concentration measurement can be used to differentiate among thymic epithelial tumours using single-phase scanning. • IHU and IC were lower in high-risk thymomas/carcinomas than in low-risk thymomas • IHU and IC were lower in advanced-stage thymomas than in early-stage thymomas • Dual-energy CT helps differentiate among thymic epithelial tumours.

Patterns of metastasis and recurrence in thymic epithelial tumours: longitudinal imaging review in correlation with histological subtypes

To determine the patterns of metastasis and recurrence in thymic epithelial tumours based on longitudinal imaging studies, and to correlate the patterns with World Health Organization (WHO) histological classifications. Seventy-seven patients with histopathologically confirmed thymomas (n=62) and thymic carcinomas (n=15) who were followed with cross-sectional follow-up imaging after surgery were retrospectively studied. All cross-sectional imaging studies during the disease course were reviewed to identify metastasis or recurrence. The sites of involvement and the time of involvement measured from surgery were recorded. Metastasis or recurrence was noted in 24 (31%) of the 77 patients. Patients with metastasis or recurrence were significantly younger than those without (median age: 46 versus 60, respectively; p=0.0005), and more commonly had thymic carcinomas than thymomas (p=0.002). The most common site of involvement was the pleura (17/24), followed by the lung (9/24), and thoracic nodes (9/24). Abdominopelvic involvement was noted in 12 patients, most frequently in the liver (n=8). Lung metastasis was more common in thymic carcinomas than thymomas (p=0.0005). Time from surgery to the development of metastasis or recurrence was shortest in thymic carcinoma, followed by high-risk thymomas, and was longest in low-risk thymoma (median time in months: 25.1, 68.8, and not reached, respectively; p=0.0015). The patterns of metastasis and recurrence of thymic epithelial tumours differ significantly across histological subgroups, with thymic carcinomas more commonly having metastasis with shorter length of time after surgery. The knowledge of different patterns of tumour spread may contribute to further understanding of the biological and clinical behaviours of these tumours.

Differentiating the grades of thymic epithelial tumor malignancy using textural features of intratumoral heterogeneity via (18)F-FDG PET/CT.

We aimed to explore the ability of textural heterogeneity indices determined by (18)F-FDG PET/CT for grading the malignancy of thymic epithelial tumors (TETs). We retrospectively enrolled 47 patients with pathologically proven TETs who underwent pre-treatment (18)F-FDG PET/CT. TETs were classified by pathological results into three subgroups with increasing grades of malignancy: low-risk thymoma (LRT; WHO classification A, AB and B1), high-risk thymoma (B2 and B3), and thymic carcinoma (TC). Using (18)F-FDG PET/CT, we obtained conventional imaging indices including SUVmax and 20 intratumoral heterogeneity indices: i.e., four local-scale indices derived from the neighborhood gray-tone difference matrix (NGTDM), eight regional-scale indices from the gray-level run-length matrix (GLRLM), and eight regional-scale indices from the gray-level size zone matrix (GLSZM). Area under the receiver operating characteristic curve (AUC) was used to demonstrate the abilities of the imaging indices for differentiating subgroups. Multivariable logistic regression analysis was performed to show the independent significance of the textural indices. Combined criteria using optimal cutoff values of the SUVmax and a best-performing heterogeneity index were applied to investigate whether they improved differentiation between the subgroups. Most of the GLRLM and GLSZM indices and the SUVmax showed good or fair discrimination (AUC >0.7) with best performance for some of the GLRLM indices and the SUVmax, whereas the NGTDM indices showed relatively inferior performance. The discriminative ability of some of the GLSZM indices was independent from that of SUVmax in multivariate analysis. Combined use of the SUVmax and a GLSZM index improved positive predictive values for LRT and TC. Texture analysis of (18)F-FDG PET/CT scans has the potential to differentiate between TET tumor grades; regional-scale indices from GLRLM and GLSZM perform better than local-scale indices from the NGTDM. The SUVmax and heterogeneity indices may have complementary value in differentiating TET subgroups.

Value of 18F-FDG PET/CT for Predicting the World Health Organization Malignant Grade of Thymic Epithelial Tumors: Focused in Volume-Dependent Parameters.

We investigated whether preoperative parameters of 18F-FDG PET/CT were correlated with the World Health Organization (WHO) classification and/or Masaoka staging of thymic epithelial tumors. We reviewed 61 patients retrospectively who were diagnosed with thymic epithelial tumors after surgical resection and PET/CT. A volume of interest was drawn on the primary lesion, using an SUV cutoff of 2.5, and metabolic indices such as SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. There were 24 male patients (38.7%), and the mean (SD) age was 50.23 (12.54) years. The mean (SD) tumor size was 6.11 (3.41) cm. There were 22 low-risk thymomas (36.9%) (A, AB, B1), 32 high-risk thymomas (51.6%), and 7 thymic carcinomas (11.5%). The Masaoka stage was I in 15 (24.6%), II in 30 (49.2%), III in 11 (18.0%), and IV in 5 patients (8.2%). Mean (SD) SUVmax was 3.43 (1.01) in low-risk thymomas, 4.42 (1.70) in high-risk thymomas, and 8.23 (2.61) in thymic carcinoma; the differences were significant (P < 0.001). Mean (SD) MTV and TLG were 90.74 (114.56) and 229.36 (300.56) in low-risk thymomas, 80.82 (112.49) and 233.93 (340.91) in high-risk thymomas, and 90.63 (90.74) and 390.94 (437.62), respectively, in thymic carcinomas. MTV and TLG showed no correlation with the WHO classification. On receiver operating characteristic curve analysis, the cutoff value for discriminating thymomas and thymic carcinomas was 5.05. SUVmax and TLG were correlated with Masaoka stage. Although volume-dependent parameters were not correlated with the WHO classification, a significant relationship was observed between SUVmax and WHO classification and Masaoka stage.

Diffusion-weighted magnetic resonance imaging of thymoma: ability of the Apparent Diffusion Coefficient in predicting the World Health Organization (WHO) classification and the Masaoka-Koga staging system and its prognostic significance on disease-free survival.

To evaluate the usefulness of diffusion-weighted magnetic resonance for distinguishing thymomas according to WHO and Masaoka-Koga classifications and in predicting disease-free survival (DFS) by using the apparent diffusion coefficient (ADC). Forty-one patients were grouped based on WHO (low-risk vs. high-risk) and Masaoka-Koga (early vs. advanced) classifications. For prognosis, seven patients with recurrence at follow-up were grouped separately from healthy subjects. Differences on ADC levels between groups were tested using Student-t testing. Logistic regression models and areas under the ROC curve (AUROC) were estimated. Mean ADC values were different between groups of WHO (low-risk = 1.58 ± 0.20 × 10(-3)mm(2)/sec; high-risk = 1.21 ± 0.23 × 10(-3)mm(2)/sec; p < 0.0001) and Masaoka-Koga (early = 1.43 ± 0.26 × 10(-3)mm(2)/sec; advanced = 1.31 ± 0.31 × 10(-3)mm(2)/sec; p = 0.016) classifications. Mean ADC of type-B3 (1.05 ± 0.17 × 10(-3)mm(2)/sec) was lower than type-B2 (1.32 ± 0.20 × 10(-3)mm(2)/sec; p = 0.023). AUROC in discriminating groups was 0.864 for WHO classification (cut-point = 1.309 × 10(-3)mm(2)/sec; accuracy = 78.1%) and 0.730 for Masaoka-Koga classification (cut-point = 1.243 × 10(-3)mm(2)/sec; accuracy = 73.2%). Logistic regression models and two-way ANOVA were significant for WHO classification (odds ratio[OR] = 0.93, p = 0.007; p < 0.001), but not for Masaoka-Koga classification (OR = 0.98, p = 0.31; p = 0.38). ADC levels were significantly associated with DFS recurrence rate being higher for patients with ADC ≤ 1.299 × 10(-3)mm(2)/sec (p = 0.001; AUROC, 0.834; accuracy = 78.0%). ADC helps to differentiate high-risk from low-risk thymomas and discriminates the more aggressive type-B3. Primary tumour ADC is a prognostic indicator of recurrence. • DW-MRI is useful in characterizing thymomas and in predicting disease-free survival. • ADC can differentiate low-risk from high-risk thymomas based on different histological composition • The cutoff-ADC-value of 1.309 × 10 (-3) mm (2) /sec is proposed as optimal cut-point for this differentiation • The ADC ability in predicting Masaoka-Koga stage is uncertain and needs further validations • ADC has prognostic value on disease-free survival and helps in stratification of risk.

Adjuvant treatment in patients at high risk of recurrence of thymoma: efficacy and safety of a three-dimensional conformal radiation therapy regimen.

BackgroundThe clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma.MethodsTwenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44–60) Gy was delivered to the tumor bed by 6–20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter.ResultsTwo of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered.ConclusionAdjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma.

Diffusion-weighted MR imaging in thymic epithelial tumors: correlation with World Health Organization classification and clinical staging.

To assess thymic epithelial tumors with diffusion-weighted magnetic resonance (MR) imaging. Informed consent from patients and institutional review board approval were obtained. Prospective study was conducted on 30 consecutive patients (21 men and nine women; age range, 35-71 years) with thymic epithelial tumors. They underwent true fast imaging with steady-state precession and single-shot echo-planar diffusion-weighted MR imaging of the mediastinum with b values of 0, 400, and 800 sec/mm(2). Apparent diffusion coefficient (ADC) of the thymic epithelial tumors was calculated by the same observer at two settings and was correlated with World Health Organization classification and clinical staging. There was significant difference in longest diameter (P = .001) and necrotic part of the tumor (P = .014) between low-risk thymoma, high-risk thymoma, and thymic carcinoma. Mean ADC value of both readings of thymic epithelial tumors (n = 30) was 1.24 × 10(-3) mm(2)/sec and 1.22 × 10(-3) mm(2)/sec, with good intraobserver agreement (κ = 0.732). There was significant difference in both readings (P = .01 and .20) of low-risk thymoma (1.30 × 10(-3) mm(2)/sec and 1.29 × 10(-3) mm(2)/sec), high-risk thymoma (1.16 × 10(-3) mm(2)/sec and 1.14 × 10(-3) mm(2)/sec), and thymic carcinoma (1.18 × 10(-3) mm(2)/sec and 1.06 × 10(-3) mm(2)/sec). Cutoff ADC values of both readings used to differentiate low-risk thymoma from high-risk thymoma and thymic carcinoma were 1.25 and 1.22 × 10(-3) mm(2)/sec with area under the curve of 0.804 and 0.851, respectively. There was significant difference in both readings of ADC value of early (stage I, II) and advanced stages (stage III, IV) of thymic epithelial tumors (P = .006 and .005, respectively). ADC value is a noninvasive, reliable, and reproducible imaging parameter that may help to assess and characterize thymic epithelial tumors.

Is a positron emission tomography–computed tomography scan useful in the staging of thymic epithelial neoplasms?: Table 1:

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed concerned the employment of 18-fluorine fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT) in the preoperative evaluation of thymic epithelial neoplasms (TENs). We reviewed its role as a predictor of Masaoka stage and histology (according to the WHO). In clinical practice, stage is considered the most important determinant in the therapeutic approach. A total of 265 papers were found as a result of the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. All the studies are retrospective analyses. Patient numbers varied from 13 to 58. Our research showed that PET-CT could clearly add information about the histology of the tumour. Thymic carcinoma constantly showed a higher standard uptake value (SUVmax) than thymomas. Furthermore, in one retrospective study of 36 patients, when using a derived PET indicator, the T/M ratio (ratio between SUVmax of the tumour and SUVmax of mediastinum, as conventionally measured at the level of the aortic arc), PET-CT could also differentiate between low- and high-risk thymomas (low risk vs high risk P = 0.01). In another study, a cut-off value of T/M ratio of 2.75 was identified between low- and high-risk TENs. The role of PET-CT in prediction of stage is harder to recognize. In one study, there was a statistically significant correlation between SUVmax, T/M ratio and Masaoka stage (P = 0.781 and 0.718, respectively). When analysing the data from the three larger series on this topic (58, 51 and 47 patients, the latter group selected in a multicentre study), only one study identified a correlation between SUVmax and Masaoka stage (Spearman correlation coefficient 0.30, P = 0.0436), while the other two failed to identify a relationship between SUVmax and stage. In three retrospective studies, PET-CT identified otherwise undetected distant metastases, thereby modifying the clinical approach. Actually, when evaluating the correlation between stage and PET-CT indicators (in particular SUVmax), results are controversial and would need further speculation.

18Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography total glycolytic volume in thymic epithelial neoplasms evaluation: a reproducible image biomarker

(18)Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography is not yet accepted as a standard pretreatment evaluation of thymic epithelial neoplasm (TEN). Statistical correlation between standardized uptake value of tumor/mediastinum ratio and patients' WHO risk class has been reported. PET metabolic tumor volume (MTV) and total glycolytic volume (TGV) have been reported as additional prognostic imaging biomarkers in several human tumors. Purpose of study was to establish whether MTV and TGV add prognostic information in TEN. A retrospective dynamic cohort study of prospectively collected data (2006-2012) on 23 consecutive patients with pathologically proven TEN (no thymic carcinoma) was conducted. All patients underwent chest CT, and PET for staging. SUV T/M ratio, semi-quantitative and volumetric analyses of TEN were calculated. Patients were categorized according to WHO classification (low-risk and high-risk thymomas). Statistical analysis was performed with bootstrap method. Multi-collinearity was established using Pearson correlation coefficient. Cut-off point for TGV was compared using Mantel Cox log rank test. SUV T/M ratio, MTV, and TGV correlate with low- and high-risk TEN. However, the statistical correlation between TGV and WHO classification (ρ=0.897) was higher than SUV T/M ratio (ρ=0.873). Since sample distributions were not uniformly smooth, only one cut-off value was identified: a TGV of 383 served as a cut-off value between low-risk and high-risk TEN. TGV is a PET reproducible imaging marker in patients with TEN, provides prognostic information, and could be useful in pretreatment stratification of patients. Nevertheless, it needs validation in larger cohort studies.

18F-fluorodeoxyglucose positron emission tomography for evaluation of thymic epithelial tumors: utility for World Health Organization classification and predicting recurrence-free survival

(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) plays an important role in many oncological settings. In this study, we assessed the utility of (18)F-FDG-PET for predicting the histological classification, stage and survival of thymic epithelial tumors. We retrospectively analyzed 37 patients with thymic epithelial tumors who underwent PET before surgical resection and investigated the relationship between the maximum of standardized uptake value (SUVmax) of each tumor and the WHO classification, recurrence-free survival, and tumor-related gene expressions. The study included 15 males and 22 females, ranging in age from 22 to 81 years (mean 64 years). The tumor histology of 31 tumors was thymoma and that of the remaining tumors was thymic carcinoma. The Masaoka tumor stage was as follows: stage I in 18, II in 9, III in 5 and IV in 5 patients. The patients were divided into three groups according to a simplified histologic classification: low-risk thymoma (types A, AB and B1, n = 21), high-risk thymoma (types B2 and B3, n = 10) and thymic carcinoma (n = 6). The SUVmax of low-risk group (SUVmax ≤4.27) was significantly lower than that of high-risk group (p = 0.0114) and that of thymic carcinomas (SUVmax >4.27) was also significantly higher than that of thymomas (p < 0.0001). The group of high SUVmax (SUVmax >4.27) had significantly inferior recurrence-free survival to that of less value (SUVmax ≤4.27) (p = 0.0009). The SUVmax were not correlated with tumor-related gene expressions. The SUVmax of (18)F-FDG-PET reflects WHO classification of thymic epithelial tumors. High SUVmax predicts lower recurrence-free survival of the tumors.

Diagnostic Utility of PET CT in Thymic Tumours with Emphasis on 68Ga-DOTATATE PET CT in Thymic Neuroendocrine Tumour - Experience at a Tertiary Level Hospital in India.

18 Fluorine-fluoro-2-deoxyglucose positron emis-sion tomography/computed tomography (18F- FDG-PET/CT) is of importance in assessing high-risk thymoma and thymic carcinomas. Detection of advanced thymoma versus thymic carcinoma by routine cross sectional anatomical imaging such as computed tomography (CT), magnetic resonance imaging (MRI) often poses a diagnostic dilemma. In this case series we observed the utility of FDG uptake to predict advanced thymoma and distinguish thymoma from thymic cancer. We reviewed 18F- FDG-PET/CT scans of 12 patients (8 males, 4 females); age 24-60yrs with thymic epithelial malignancy from January 2011 to May 2013. FDG activity in lesions was quantified using maximum standardised uptake value (SUVmax) and correlated with Masaoka staging and WHO classification. All patients fasted 4 hr prior to 18F-FDG PET/CT. Images from vertex to mid-thigh were acquired 60min post injection of 3.7 -4.7 MBq/kg (Mega Becquerel)/kilogram of18F-FDG and SUV max of each tumour was measured. One patient underwent DOTATATE scan, received 138MBq of 68Gallium (68Ga)-DOTATATE injection IV and imaging was done after 60 min. Higher FDG uptake of SUVmax 7.35 was seen in type B3 thymoma. FDG uptake was higher in thymic carcinoma (20.45 in primary and 17.46 in the node) or neuroendocrine differentiation (NED) than in patients with thymomas (ranged 7.35 - 3.02). No significant association was observed between higher focal FDG uptake and advanced-stage disease in thymoma. In NED 68Ga - DOTATATE imaging identified more lesions than in FDG. PET CT is a valuable diagnostic tool in evaluation of thymic tumours, to assess in initial workup, for treatment response and for prognostication. 68Ga-DOTATATE PET/CT is beneficial in assessing neuroendocrine thymic tumours. Focal FDG uptake cannot predict advanced thymoma but is helpful in distinguishing thymoma from thymic carcinoma, or the more aggressive thymoma B3.

Role of combined 18F-FDG-PET/CT for predicting the WHO malignancy grade of thymic epithelial tumors: A multicenter analysis

IntroductionTo investigate the performance of combined 18F-FDG-PET/CT as a predictor of the WHO-classification based malignancy grade in thymic epithelial tumors. MethodsFrom 05/06 to 02/12, the data of 47 patients with thymic epithelial tumors assessed by 18F-FDG-PET/CT before being surgically treated were collected in 3 centers and retrospectively reviewed for the purposes of this study. The SUVmax and the SUVmax/T index (the ratio tumor-SUVmax to tumor-size) have been matched with specific subgroups of the WHO-classification: low-risk thymomas (types A–AB–B1), high-risk thymomas (types B2–B3) and thymic carcinomas (type C). ResultsThere were 22 men and 25 women (age range: 31–84 yrs). Mean tumor size was 44.7±19.0mm. The WHO-classification was: type-A #2, type-AB #11, type-B1 #9, type-B2 #9, type-B3 #9 and type-C #7. The SUVmax and the SUVmax/T were found to be predictive factors useful to distinguish thymomas from thymic carcinomas (SUVmax: area under ROC-curve: 0.955, p=0.0045; SUVmax/T-size: area under ROC-curve: 0.927, p=0.0022). Moreover, both parameters were found to be correlated with the WHO malignancy grade (low-risk thymomas; high-risk thymomas; thymic carcinoma), Spearman correlation coefficients being 0.56 (p<0.0001) and 0.76 (p<0.0001), respectively for the SUVmax and for the SUVmax/T index. In addition, the SUVmax is also significantly correlated with Masaoka stage (Spearman correlation coefficient: 0.30, p=0.0436) ConclusionsA significant relationship was observed between 18F-FDG-PET/CT findings and histologic WHO-classification for this cohort of thymic epithelial tumors. Thus, on the basis of these evidences, we infer that 18F-FDG-PET/CT may be useful to predict histology and the WHO classes of risk.

18F-fluorodeoxyglucose positron emission tomography/computed tomography and the relationship between fluorodeoxyglucose uptake and the expression of hypoxia-inducible factor-1 , glucose transporter-1 and vascular endothelial growth factor in thymic epithelial tumours

The objective of this study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the relationships among the expressions of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF), histological type, other clinical factors and FDG uptake in thymic epithelial tumours. Thirty-three patients who underwent FDG-PET/CT before treatment were reviewed. All types of tumours were reclassified into three subgroups: low-risk thymomas (types A, AB and B1), high-risk thymomas (types B2 and B3) and thymic carcinomas. Tumour contour, pattern of FDG uptake, tumour size and maximum standardized uptake value (SUVmax) were obtained. Expressions of HIF-1α, Glut-1 and VEGF were analysed immunohistochemically, and these expressions were evaluated using grading scales. FDG uptake was visually recognized in all (100%) tumours. A homogeneous pattern of FDG uptake was increasingly observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas (P = 0.016). SUVmax for thymic carcinomas was significantly higher than that for thymomas (P = 0.008). With the optimal cut-off value of SUVmax of 5.6, the sensitivity, specificity and accuracy for diagnosing thymic carcinoma were 0.75, 0.80 and 0.79, respectively. Regarding the mean scoring of HIF-1α, Glut-1 and VEGF, increasing trends were observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas. Tumour size revealed a significant correlation with SUVmax (r = 0.60, P < 0.001), and the expression of HIF-1α showed a moderate association, but the expression of Glut-1 showed no correlation with SUVmax. Regarding correlations between the expression of the three markers, there were moderate associations between HIF-1α and Glut-1, and HIF-1α and VEGF, and a significant correlation between Glut-1 and VEGF (r = 0.60, P < 0.001). In type B1 thymoma, HIF-1α and Glut-1 were partly expressed in non-neoplastic immature lymphocytes. FDG-PET/CT should be performed in patients with tumours in the anterior mediastinum because the pattern of FDG uptake and SUVmax are useful in the differential diagnosis of thymic epithelial tumours. Furthermore, the expressions of HIF-1α, Glut-1 and VEGF might be associated with malignancy of thymic epithelial tumours. In contrast, FDG uptake might be dependent on tumour size rather than Glut-1 overexpression.