Assessing the role of <Superscript>18</Superscript>F-FDG PET and <Superscript>18</Superscript>F-FDG PET/CT in the diagnosis of soft tissue musculoskeletal malignancies: a systematic review and meta-analysis

Purpose

Twelve years ago a meta-analysis evaluated the diagnostic performance of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in assessing musculoskeletal soft tissue lesions (MsSTL). Currently, PET/CT has substituted PET imaging; however, there has not been any published meta-analysis on the use of PET/CT or a comparison of PET/CT with PET in the diagnosis of MsSTL. Therefore, we conducted a meta-analysis to identify the current diagnostic performance of ¹⁸F-FDG PET/CT and determine if there is added value when compared to PET.

Methods

A systematic review of English articles was conducted, and MEDLINE PubMed, the Cochrane Library, and Embase were searched from 1996 to March 2015. Studies exploring the diagnostic accuracy of ¹⁸F-FDG PET/CT (or dedicated PET) compared to histopathology in patients with MsSTL undergoing investigation for malignancy were included.

Results

Our meta-analysis included 14 articles composed of 755 patients with 757 soft tissue lesions. There were 451 (60 %) malignant tumors and 306 benign lesions. The ¹⁸F-FDG PET/CT (and dedicated PET) mean sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for diagnosing MsSTL were 0.96 (0.90, 1.00), 0.77 (0.67, 0.86), 0.88 (0.85, 0.91), 0.86 (0.78, 0.94), and 0.91 (0.83, 0.99), respectively. The posterior mean (95 % highest posterior density interval) for the AUC was 0.92 (0.88, 0.96). PET/CT had higher specificity, accuracy, and positive predictive value when compared to a dedicated PET (0.85, 0.89, and 0.91 vs 0.71, 0.85, and 0.82, respectively).

Conclusion

¹⁸F-FDG PET/CT and dedicated PET are both highly accurate in the diagnosis of MsSTL. PET/CT is more accurate and specific and has a higher positive predictive value than PET.

     

Prospective comparison of combined <Superscript>18</Superscript>F-FDG and <Superscript>18</Superscript>F-NaF PET/CT vs. <Superscript>18</Superscript>F-FDG PET/CT imaging for detection of malignancy

Purpose  

Typically, ¹⁸F-FDG PET/CT and ¹⁸F-NaF PET/CT scans are done as two separate studies on different days to allow sufficient time for the radiopharmaceutical from the first study to decay. This is inconvenient for the patients and exposes them to two doses of radiation from the CT component of the examinations. In the current study, we compared the clinical usefulness of a combined ¹⁸F-FDG/¹⁸F-NaF PET/CT scan with that of a separate ¹⁸F-FDG-only PET/CT scan.     

The management of pyothorax-associated lymphoma using <Superscript>18</Superscript>F-FDG PET/CT

Objective  

Pyothorax-associated lymphoma (PAL) is a rare form of lymphoma and its management on ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined computed tomography (CT) has not been well reported. The purpose of this study was to evaluate the usefulness of FDG PET/CT in patients with PAL.     

Efficacy of conventional whole-body <Superscript>18</Superscript>F-FDG PET/CT in the incidental findings of parotid masses

Objective  

The objective of this study was to evaluate the incidence of incidental parotid masses with conventional whole-body ¹⁸F-deoxyglucose (FDG) PET/CT and assess the ability of PET/CT to characterize these unexpected parotid lesions.     

<Superscript>18</Superscript>F-FDG PET/CT in sarcoidosis management: review and report of 20 cases

PURPOSE: To evaluate the interest of (18)F-fluoro-2-deoxy-D: -glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for diagnosis and therapeutic follow-up of patients with sarcoidosis. METHODS: Twenty consecutive patients with biopsy-proven sarcoidosis were retrospectively included, in particular, 13 and seven cases of thoracic and extra-thoracic sarcoidosis, respectively. All patients underwent (18)F-FDG PET/CT, and 12 of them also (67)Ga scintigraphy. Five patients were re-examined by (18)F-FDG PET/CT to assess response to corticosteroid (CS) treatment. RESULTS: Sensitivity of (18)F-FDG PET/CT in detecting active sarcoidosis localizations was determined considering only biopsy-proven sites. For thoracic, sinonasal, and pharyngo-laryngeal localizations, (18)F-FDG PET/CT sensitivity was 100%, 100%, and 80%, respectively. Overall sensitivity for all 36 biopsy-proven localizations improved from 78% to 87% after excluding skin involvement. Considering only the 12 patients who underwent both scintigraphic examinations, overall sensitivity of (67)Ga scintigraphy and (18)F-FDG PET/CT was 58% and 79%, respectively and improved to 67% and 86% after excluding all sites of skin involvement. To evaluate the efficacy of CS treatment, five enrolled patients underwent second (18)F-FDG PET/CT. Complete regression of all foci of pathological tracer uptake was showed in two cases, permitting CS withdrawal after 2 and 6 months. Improvement but incomplete regression of mediastino-pulmonary disease occurred in two patients treated with CS for 19 and 21 months. Disease progression was assessed in one patient treated with decreasing doses of CS during 16 months. CONCLUSION: (18)F-FDG PET/CT allows to obtain a complete morpho-functional cartography of inflammatory active localizations and to follow treatment efficacy in patients with sarcoidosis, particularly in atypical, complex, and multisystemic forms.     

The incremental value of <Superscript>18</Superscript>F-FDG PET/CT in paediatric malignancies

PURPOSE: (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) imaging has been used in the assessment of paediatric malignancies. PET/CT increases the diagnostic accuracy in adult cancer patients. The present study assesses the incremental value of FDG PET/CT in paediatric malignancies. METHODS: A total of 118 (18)FDG PET/CT studies of 46 paediatric patients were reviewed retrospectively. PET and PET/CT results were classified as malignant, equivocal or benign, compared on a site- and study-based analysis, and also compared with the clinical outcome. RESULTS: Three hundred and twenty-four sites of increased FDG uptake were detected. Discordant PET and PET/CT interpretations were found in 97 sites (30%) in 27 studies (22%). PET yielded a statistically significant higher proportion of equivocal and a lower proportion of benign lesion and study results (p<0.001) than PET/CT. With PET there were 153 benign (47%), 84 (26%) equivocal and 87 (27%) malignant sites, while PET/CT detected 226 benign (70%), 10 (3%) equivocal and 88 (27%) malignant lesions. PET/CT mainly improved the characterisation of uptake in brown fat (39%), bowel (17%), muscle (8%) and thymus (7%). The study-based analysis showed that 17 equivocal and seven positive PET studies (20%) were interpreted as benign on PET/CT, while three equivocal studies were interpreted as malignant. The study-based sensitivity and specificity of PET/CT were 92% and 78% respectively. CONCLUSION: PET/CT significantly improved the characterisation of abnormal (18)FDG foci in children with cancer, mainly by excluding the presence of active malignancy in sites of increased tracer activity.     

<Superscript>18</Superscript>F-FDG and <Superscript>18</Superscript>F-FLT PET/CT imaging in the characterization of mediastinal lymph nodes

Purpose

There is currently no single modality for accurate characterization of enlarged mediastinal lymph nodes into benign or malignant. Recently ¹⁸F-fluorothymidine (FLT) has been used as a proliferation marker. In this prospective study, we examined the role of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) and ¹⁸F-FLT PET/CT in categorizing mediastinal lymph nodes as benign or malignant.

Materials and methods

A total of 70 consecutive patients with mediastinal lymphadenopathy detected on computed tomography (CT) or chest radiograph underwent whole body ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT (within 1 week of each other). Lymph nodal tracer uptake was determined by calculation of standardized uptake value (SUV) with both the tracers. Results of PET/CT were compared with histopathology of the lymph nodes.

Results

Histopathology results showed thirty-seven patients with sarcoidosis, seven patients with tuberculosis, nine patients with non-small cell lung cancer, five patients with Hodgkin’s lymphoma and twelve patients with non-Hodgkin’s lymphoma. The mean FDG SUV_max of sarcoidosis, tuberculosis, Hodgkin’s and non-Hodgkin’s lymphoma was 12.7, 13.4, 8.2, and 8.8, respectively, and the mean FLT SUV_max was 6.0, 5.4, 4.4, and 3.8, respectively. It was not possible to characterize mediastinal lymphadenopathy as benign or malignant solely based on FDG SUV_max values (p > 0.05) or FLT SUV_max values (p > 0.05). There was no significant difference in FDG uptake (p > 0.9) or FLT uptake (p > 0.9) between sarcoidosis and tuberculosis. In lung cancer patients, the FDG SUV_max and FLT SUV_max of those lymph nodes with tumor infiltration on biopsy was 6.7 and 3.9, respectively, and those without nodal infiltration was 6.4 and 3.7, respectively, and both the tracers were not able to characterize the nodal status as malignant or benign (p > 0.05).

Conclusion

Though ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT reflect different aspects of biology, i.e., proliferation and metabolism, respectively, neither tracer could provide satisfactory categorization of benign and malignant lymph nodes. The results of this study clearly suggest that differentiation of mediastinal nodes into benign and malignant solely based on SUV_max values cannot be relied upon, especially in settings where tuberculosis and sarcoidosis are common.

     

<Superscript>18</Superscript>FDG PET scanning of benign and malignant musculoskeletal lesions

OBJECTIVE: To describe the technique, applications and advantages of (18)FDG PET scanning in detection, analysis and management of musculoskeletal lesions. DESIGN AND PATIENTS: Forty-five patients (19 males,26 females) aged 9 to 81 years had radiographs, routine radionuclide scans, CT and/or MRI of clinically suspected active benign or malignant musculoskeletal lesions. (18)FDG scans with a Siemens ECAT EXACT 921 dedicated PET unit (Knoxville, Tenn.) and FWH=6 mm images acquired as a 5-6 bed examination (6 min emission and 4 min transmission) used OSEM iterative reconstruction with segmented transmission attenuation correction and a Gaussian filter (cutoff 6.7 mm). Region of interest (ROI) 3x3 pixel image analysis based on transverse whole body images (slice thickness 3.37 mm) generated Maximum Standard Uptake Values (Max SUV) with a cutoff of 2.0 used to distinguish benign and malignant lesions. RESULTS: Thirty-nine studies were available for SUV ROI analysis. Overall sensitivity for differentiating malignant from benign osseous and non-osseous lesions was 91.7% (22/24), overall specificity was 100% (11/11) with an accuracy of 91.7%. All aggressive lesions had a Max SUV >2.0. Data separating benign from malignant lesions and aggressive from benign lesions were statistically significant ( P<0.001) in both categories. There was no statistically significant difference in distinguishing aggressive from malignant lesions ( P, ns). CONCLUSION: (18)FDG PET contributes unique information regarding metabolism of musculoskeletal lesions. By supplying a physiologic basis for more informed treatment and management, it influences prognosis and survival. Moreover, since residual, recurrent or metastatic tumors can be simultaneously documented on a single whole body scan, PET may theoretically prove to be cost-effective.     

<Superscript>18</Superscript>F-FDG PET/CT in inflammatory pseudotumor of the colon causing intussusception

Inflammatory pseudotumor is a rare benign lesion mimicking malignancy both clinically and radiologically. An accurate diagnosis is still difficult and is based on the histological examination. Since inflammatory pseudotumor is exceptionally rare in the colon, this unexpected lesion can be mistaken for malignancy. We report the first case of inflammatory pseudotumor in the colon that showed ¹⁸F-fluorodeoxyglucose (FDG) uptake and acted as the lead point causing colocolic intussusception.     

The impact of <Superscript>18</Superscript>F-FDG PET/CT in patients with liver metastases

Purpose The aim of this study was to assess the performance of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) versus dedicated contrast-enhanced CT (CECT) in the detection of metastatic liver disease. Methods All patients that presented to our Institution with suspected metastatic liver disease who underwent ¹⁸F-FDG PET/CT and CECT within 6 weeks of each other, were retrospectively analyzed, covering a 5-year period. One hundred and thirty-one patients (67 men, 64 women; mean age 62) were identified. Seventy-five had colorectal carcinoma and 56 had other malignancies. The performance of CECT and that of ¹⁸F-FDG-PET/CT in detecting liver metastases were compared. The ability of each to detect local recurrence, extrahepatic metastases and to alter patient management was recorded. The final diagnosis was based on histology, clinical and radiological follow-up (mean 23 months). Results In detecting hepatic metastases, ¹⁸F-FDG-PET/CT yielded 96% sensitivity and 75% specificity, whilst CECT showed 88% sensitivity and 25% specificity. ¹⁸F-FDG-PET/CT and CECT were concordant in 102 out of 131 patients (78%). In the colorectal group ¹⁸F-FDG-PET/CT showed 94% sensitivity and 75% specificity, whilst CECT had 91% sensitivity and 25% specificity. In the noncolorectal group ¹⁸F-FDG-PET/CT showed 98% sensitivity and 75% specificity whilst CECT had 85% sensitivity and 25% specificity. Overall, ¹⁸F-FDG-PET/CT altered patient management over CECT in 25% of patients. CECT did not alter patient management over ¹⁸F-FDG-PET/CT alone in any patients. Conclusion ¹⁸F-FDG-PET/CT performed better in detecting metastatic liver disease than CECT in both colorectal and noncolorectal malignancies, and frequently altered patient management. The future role of CECT in these patients may need to be re-evaluated to avoid potentially unnecessary duplication of investigation where ¹⁸F-PET/CT is readily available. Authors stated no financial relationship to disclose     

<Superscript>18</Superscript>F-FDG PET/CT in paediatric lymphoma: comparison with conventional imaging

Purpose  

In children with Hodgkin’s disease and non-Hodgkin’s lymphoma, the ability of ¹⁸F-fluoro-2-deoxy-D-glucose PET/CT and conventional imaging (CI) to detect malignant lesions and predict poor lesion response to therapy was assessed and compared.     

The role of <Superscript>18</Superscript>F-FDG PET/CT in the detection of osteosarcoma recurrence

Aim

The aim of this study was to investigate the diagnostic accuracy of ¹⁸F-FDG-PET/CT in osteosarcoma patients suspicious for disease recurrence after adequate surgical therapy.

Methods

Inclusion criteria were: a) adequate surgical treatment for proven osteosarcoma and documented complete remission after therapy; b) ¹⁸F-FDG-PET/CT performed during follow-up for clinical/diagnostic suspicion of relapse; c) new surgical treatment with excision of the suspected lesions; d) histological validation of ¹⁸F-FDG-PET/CT findings. Thirty-seven patients matching all inclusion criteria were retrospectively enrolled (20 men and 17 female). Primary surgical treatment consists of resection (31 cases) or amputation (six cases). ¹⁸F-FDG-PET/CT performance was assessed with a per-patient and per-site evaluation of sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV). The sites of relapse were classified as local, lung, lymphnodes (LNs), and distant (other skeletal segments and/or distant soft tissue). The disease-free survival (DFS) and the overall survival (OS) after 18F-FDG PET/CT were evaluated.

Results

¹⁸F-FDG-PET/CT was positive in 89.2% (33/37) of patients. Local uptake only was observed in 35.1% patients (13/37); lung uptake only in 18.9% (7/37); distant uptake only in 2.7% (1/37) case; multiple sites of uptake in 32.4% (12/37). Histology resulted positive in 92% (34/37) of patients. A total of 51 pathologic lesions were evaluated (22 local relapse, 11 lung metastasis, 10 metastatic LNs, eight distant metastatic lesions). On a per-patient analysis ¹⁸F-FDG-PET/CT showed a sensitivity, specificity, accuracy, PPV, and NPV of 91%, 75%, 89%, 97%, 50%. On a per-site analysis the performance for local relapse was 96%, 100%, 97%, 100%, 93%, while for lung relapse detection was 80%, 100%, 92%, 100%, 88%. The mean follow-up after ¹⁸F-FDG-PET/CT was 21.5 months. At the last follow-up, 19% (7/37) of patients were death with disease, 38% (14/37) were alive with disease, and 43% (16/37) had no evidence of disease. Overall survival was 90% and 75% at 24 and 60 months, respectively.

Conclusion

¹⁸F-FDG-PET/CT showed valuable results for detecting recurrence(s) in osteosarcoma patients with suspicious of relapse after treatment, particularly in the detection of local relapse and lung metastasis.

     

Treatment response evaluation with <Superscript>18</Superscript>F-FDG PET/CT and <Superscript>18</Superscript>F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

Aim

The aim of this study was to assess the combined use of the radiotracers ¹⁸F-FDG and ¹⁸F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT).

Patients and methods

Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with ¹⁸F-FDG and ¹⁸F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD).

Results

An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, ¹⁸F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, ¹⁸F-FDG PET/CT-based treatment response revealed CR in 14 patients (¹⁸F-FDG PET/CT CR), PR in 11 patients (¹⁸F-FDG PET/CT PR) and progressive disease in four patients (¹⁸F-FDG PET/CT PD). In terms of ¹⁸F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, ¹⁸F-NaF PET/CT depicted 56 of the 129 ¹⁸F-FDG positive lesions (43 %). Follow-up ¹⁸F-NaF PET/CT showed persistence of 81.5 % of the baseline ¹⁸F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to ¹⁸F-FDG negative. Treatment response according to ¹⁸F-NaF PET/CT revealed CR in one patient (¹⁸F-NaF PET/CT CR), PR in five patients (¹⁸F-NaF PET/CT PR), SD in 12 patients (¹⁸F-NaF PET/CT SD), and PD in seven patients (¹⁸F-NaF PET/CT PD). Dynamic ¹⁸F-FDG and ¹⁸F-NaF PET/CT studies showed that SUV_average, SUV_max, as well as the kinetic parameters K₁, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p?<?0.001).

Conclusion

F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of ¹⁸F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, ¹⁸F-NaF PET/CT does not seem to add significantly to ¹⁸F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.

     

Diagnostic value of combining <Superscript>11</Superscript>C-choline and <Superscript>18</Superscript>F-FDG PET/CT in hepatocellular carcinoma

Purpose

In this prospective study, our goal was to emphasize the diagnostic value of combining ¹¹C-choline and ¹⁸F-FDG PET/CT for hepatocellular carcinoma (HCC) in patients with chronic liver disease.

Methods

Thirty-three consecutive patients were enrolled. All patients were suspected to have HCC based on CT and/or MRI imaging. A final diagnosis was obtained by histopathological examination or by imaging alone according to American Association for the Study of Liver Disease criteria. All patients underwent PET/CT with both tracers within a median of 5 days. All lesions showing higher tracer uptake than normal liver were considered positive for HCC. We examined how tracer uptake was related to biological (serum α-fetoprotein levels) and pathological (differentiation status, peritumoral capsule and vascular invasion) prognostic markers of HCC, as well as clinical observations at 6 months (recurrence and death).

Results

Twenty-eight HCC, four cholangiocarcinomas and one adenoma were diagnosed. In the HCC patients, the sensitivity of ¹¹C-choline, ¹⁸F-FDG and combined ¹¹C-choline and ¹⁸F-FDG PET/CT for the detection of HCC was 75 %, 36 % and 93 %, respectively. Serum α-fetoprotein levels >200 ng/ml were more frequent among patients with ¹⁸F-FDG-positive lesions than those with ¹⁸F-FDG-negative lesions (p?<?0.05). Early recurrence (n=2) or early death (n=5) occurred more frequently in patients with ¹⁸F-FDG-positive lesions than in those with ¹⁸F-FDG-negative lesions (p?<?0.05).

Conclusion

The combined use of ¹¹C-choline and ¹⁸F-FDG PET/CT detected HCC with high sensitivity. This approach appears to be of potential prognostic value and may facilitate the selection of patients for surgical resection or liver transplantation.

     

Role of <Superscript>18</Superscript>F-FDG PET/CT in patients affected by Langerhans cell histiocytosis

Purpose

Langerhans cell histiocytosis (LCH) is a rare hematological disorder for which the utility of¹⁸F-FDG PET/CT is unclear. Our aim was to explore the metabolic features of LCH and the possible role of¹⁸F-FDG PET/CT in LCH evaluation.

Materials and methods

We found 17 patients with histologically proven LCH who underwent 17¹⁸F-FDG PET/CT scans for staging and 42 scans for restaging/follow-up purposes. PET/CT results were compared with those obtained from other conventional imaging modalities (bone scintigraphy, plain radiogram, computed tomography, magnetic resonance).

Results

¹⁸F-FDG PET/CT was positive in 15/17 patients, and it detected 36/37 lesions; all bone and extraskeletal lesions, except for a cecal lesion, were¹⁸F-FDG-avid. Only 1/4 of the patients with lung LCH had hypermetabolic lesions. The average SUV_max of the FDG-avid lesions was 7.3 ± 6.7, the average lesion-to-liver SUV_max ratio was 3.4 ± 2.5, and the average lesion-to-blood pool SUV_max ratio was 4 ± 3.2. In comparison to other imaging methods,¹⁸F-FDG PET/CT detected additional lesions or was able to evaluate treatment response earlier in 33/74 cases; it was confirmatory in 38/74 and detected fewer lesions in 3/74 (all three with lung LCH).

Conclusions

¹⁸F-FDG PET/CT seems to be useful for evaluating LCH when compared to conventional imaging, except in pulmonary cases. It can be used both for staging and restaging purposes.