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Assessment of malignant pleural mesothelioma with 18F-FDG dual-head gamma-camera coincidence imaging: Comparison with histopathology
Abstract
Malignant pleural mesothelioma is an aggressive primary neoplasm for which early detection and accurate staging are known diagnostic challenges. The role of (18)F-FDG dual-head gamma-camera coincidence imaging ((18)F-FDG-CI) is yet to be defined. The purpose of this study was to evaluate the usefulness of (18)F-FDG-CI in the assessment of malignant pleural mesothelioma using histopathology as the gold standard.
Fifteen consecutive patients with CT scan evidence of pleural thickening, fluid, plaques, or calcification underwent (18)F-FDG imaging 1.5 h after the intravenous administration of 370 MBq (18)F-FDG. Imaging was performed with a dual-head gamma camera equipped with 2.54-cm-thick NaI crystals operating in coincidence mode. Using an iterative algorithm, whole-body images were reconstructed as transaxial, sagittal, and coronal images. No attenuation correction was applied. The results of (18)F-FDG-CI scans were compared with CT and with histopathologic diagnosis.
Eleven of 15 patients had histologically proven malignant mesotheliomas (10 epithelial, 1 sarcomatoid). All 11 primary tumors were detected by (18)F-FDG, and absence of disease was confirmed in the 4 patients who were disease free. Thirty-four lesions were biopsied; among these, 29 were found to be positive for tumor. (18)F-FDG was true-positive in 28 lesions, true-negative in 4, false-negative in 1 (0.5 cm in diameter), and false-positive in 1 (inflammatory pleuritis). The smallest lesion detected was 0.8 cm. For biopsied lesions, overall sensitivity, specificity, and accuracy for (18)F-FDG-CI were 97%, 80%, and 94% respectively, compared with 83%, 80%, and 82% for CT. Twenty-one of 29 positive lesions involved the pleura, lung parenchyma, or chest wall and were all (18)F-FDG avid. In the mediastinum, (18)F-FDG-CI detected 7 of 8 biopsy-positive lesions (88%), whereas CT was positive in 6 of 8 lesions (75%). (18)F-FDG identified extrathoracic metastases in 5 patients, excluding them from surgical therapy.
These preliminary results suggest that (18)F-FDG-CI appears to be an accurate method to diagnose and to define the extent of disease in patients with diffuse malignant pleural mesothelioma.
... Consequently, only 14 studies entered the fi nal analysis, of which four were prospective, 16,20,25,32 fi ve were retrospective, 6,15,27,29,30 and fi ve had an unrevealed design. 8,10,11,13,33 Th ese eligible studies comprised 639 patients (66% male patients) with a median age of 62 years, of whom 407 (64%) eventually had malignant eff usions (or thickening) and 232 had benign pleural conditions. Specifically, the causes of the malignant pleural effusions included 156 MPMs (98 epithelial, 20 sarcomatoid or mixed, and 38 nonspecifi ed) and 251 pleural metastases, either from lung cancer (135 non-small cell histology, seven small-cell, and 27 nonspecified), nonspecified origin (n 5 59), or miscellaneous (n 5 23). ...
... Th e intended use of the index test was to discriminate between benign and malignant pleural eff usions (or thickening) either in patients with eff usions of uncertain etiology, 8,10,11,16,20,32 a previously diagnosed lung cancer, 6,15,27,29 or a suspected or confi rmed MPM. 13,25,30,33 Moreover, FDG-PET imaging metabolic activity was interpreted by a qualitative method in seven studies, 8,10,11,13,15,16,32 a semi- quantitative method in three studies, 20,25,33 and by both in four studies. 6,27,29,30 For semiquantitative assessments over a region of interest, SUVmax optimal cutoff dis- criminating values ranged from 2.2 to 3.5. ...
... Th e intended use of the index test was to discriminate between benign and malignant pleural eff usions (or thickening) either in patients with eff usions of uncertain etiology, 8,10,11,16,20,32 a previously diagnosed lung cancer, 6,15,27,29 or a suspected or confi rmed MPM. 13,25,30,33 Moreover, FDG-PET imaging metabolic activity was interpreted by a qualitative method in seven studies, 8,10,11,13,15,16,32 a semi- quantitative method in three studies, 20,25,33 and by both in four studies. 6,27,29,30 For semiquantitative assessments over a region of interest, SUVmax optimal cutoff dis- criminating values ranged from 2.2 to 3.5. ...
Background
The role of FDG-PET imaging for diagnosing malignant pleural effusions is not well defined. The aim of this study was to summarize the evidence for its use in ruling in or out the malignant origin of a pleural effusion and/or thickening. Methods
Meta-analysis of diagnostic accuracy studies published in the Cochrane library, PubMed and Embase (inception to June 2013) without language restrictions. Two investigators selected studies that had evaluated the performance of FDG-PET in patients with pleural effusions and/or thickening, using pleural cyto- or histopathology as the reference standard for malignancy. Subgroup analyses were conducted according to FDG-PET imaging interpretation (qualitative or semi-quantitative), PET equipment (PET vs integrated PET-CT) and/or target population (known lung cancer or malignant pleural mesothelioma). Study quality was assessed using QUADAS-2. We used a bivariate random-effects model for the analysis and pooling of diagnostic performance measures across studies. ResultsFourteen non-high risk of bias studies, comprising 407 patients with malignant and 232 with benign pleural conditions met the inclusion criteria. Semi-quantitative PET readings had a significantly lower sensitivity for diagnosing malignant effusions than visual assessments (82% vs 91%, p=0.026). The pooled test characteristics of integrated PET-CT systems using semi-quantitative interpretations for identifying malignant effusions were: sensitivity 81%, specificity 74%, positive LR 3.22, negative LR 0.26, and AUC 0.838. Resultant data were heterogeneous, and spectrum bias should be considered when appraising FDG-PET operating characteristics. Conclusions
The moderate accuracy of PET-CT using semi-quantitative readings precludes its routine recommendation for discriminating malignant from benign pleural effusions. Systematic Review Registration NumberInternational Prospective Register of Systematic Reviews (PROSPERO) Identifier: CRD42011001392. http://www.crd.york.ac.uk/prospero/
... Reviewing titles and abstracts, 524 articles were excluded: 464 because they were not in the field of interest of this review, 8 because they were evaluating the diagnostic performance of 18 F-FDG-PETor PET/CT in assessing pleural lesions in patients with history of cancer (13)(14)(15)(16)(17)(18)(19)(20), 35 because they were reviews or editorials, 15 because they case reports, and 2 because they were not in English (21,22). Finally, 16 articles (including 745 patients) were selected and were eligible for the systematic review (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38); no additional study was found screening the references of these articles (Fig 1). The characteristics of the studies included in the qualitative analysis (systematic review) are presented in Tables 1-4. ...
... The characteristics of the studies included in the qualitative analysis (systematic review) are presented in Tables 1-4. Eleven articles including 212 patients had sufficient data to reassess sensitivity or specificity of 18 F-FDG-PET or PET/CT in the differential diagnosis between malignant and benign pleural lesions on a perpatient-based analysis and were included in the quantitative analysis (meta-analysis) (23)(24)(25)(26)(27)(28)30,31,33,35,37). ...
... Using the database search, 16 original articles written over the past 16 years were selected (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38); of which six were prospective studies (27)(28)(29)(30)34,37). The patient population included subjects with suspicious malignant pleural mesothelioma or who were undergoing evaluation for pleural lesions. ...
To systematically review and meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the differential diagnosis between malignant and benign pleural lesions.
A comprehensive literature search of studies published through June 2013 regarding the diagnostic performance of (18)F-FDG-PET and PET/CT in the differential diagnosis of pleural lesions was carried out. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) of (18)F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions on a per-patient-based analysis were calculated. The area under the summary receiver operating characteristic curve (AUC) was calculated to measure the accuracy of these methods. Subanalyses considering device used (PET or PET/CT) were performed.
Sixteen studies including 745 patients were included in the systematic review. The meta-analysis of 11 selected studies provided the following results: sensitivity 95% (95% confidence interval [95%CI]: 92-97%), specificity 82% (95%CI: 76-88%), LR+ 5.3 (95%CI: 2.4-11.8), LR- 0.09 (95%CI: 0.05-0.14), DOR 74 (95%CI: 34-161). The AUC was 0.95. No significant improvement of the diagnostic accuracy considering PET/CT studies only was found.
(18)F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods in the differential diagnosis between malignant and benign pleural lesions; nevertheless, possible sources of false-negative and false-positive results should be kept in mind.
... 52 This finding explains in part why the majority of mesotheliomas are FDG avid, with the intensity of uptake ranging from moderate to high, depending on the cell type. 53,54 Epithelial subtypes tend to be less metabolically active than their mixed and sarcomatoid counterparts, and in a small number of cases epithelial avidity can be very mild or absent. 53,55 FDG-PET imaging accurately differentiates benign from malignant pleural disease. ...
... Schneider and colleagues 57 reported their results on 18 consecutive patients with biopsy-proven MPM, indicating that all MPMs were FDG avid. Gerbaudo and colleagues 54 reported similar results, with an overall sensitivity, specificity, and accuracy of FDG imaging to diagnose MPM of 97%, 80% and 94%, respectively, compared with 83%, 80%, and 82% for diagnostic CT. FDG imaging correctly identified 28 of 29 malignant tumors confirmed histologically, and yielded negative results in 4 of 5 benign lesions. ...
... Furthermore, FDG-PET imaging has been of great value in guiding needle or thoracoscopic biopsy to the highest area of uptake within the thickened pleura. 54 PET/CT-guided biopsies of a variety of tumor types have increased the yield of positive findings by minimizing sampling errors from specimens containing only reactive fibrous changes and not viable tumor. 58,59 Sources of known false-positive uptake in FDG-PET images of patients with pleural lesions include asbestos-related plaques, benign inflammatory pleuritis, tuberculous pleuritis, parapneumonic effusion, and bronchopleural fistulas. ...
Early diagnosis and accurate disease staging in patients with malignant pleural mesothelioma (MPM) are essential in classifying such patients into prognostic subgroups to allow delivery of stage-specific therapies. This review addresses the current status of multimodality imaging in the diagnosis and staging of MPM. Clinical, research, and future directions in computed tomography (CT), magnetic resonance imaging, and PET/CT diagnosis and staging of MPM are discussed, including the use of novel PET probes. The article concludes with important take-home messages summarized as the pearls and pitfalls of each diagnostic modality in the diagnosis and staging of patients with MPM.
... The role of positron emission tomography (PET) and integrated PETcomputer tomography (PET-CT) with [18] F-Fluorodeoxyglucose (FDG) in predicting malignancy in patients with pleural effusion or pleural thickening is still debated. The existing three earlier systematic reviews and meta-analyses were published in 2014 and 2015, included also noneffusion pleural pathology [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22], handled bias differently, and reached different and contradictory conclusions [23][24][25]. Five studies have been published since then [26][27][28][29][30]. ...
... A total of 3487 titles were screened, leading to 57 full text assessments ( Fig. 1. Twenty-one authors were contacted to get access to an English version of the paper [35][36][37], to specify if the entire study population had pleural effusions [14,16,21,[38][39] or to obtain access to data specific for patients with pleural effusions [15,22,[10][11][12][13][17][18][19][20][40][41][42]. Three authors replied, leading to exclusion of two studies due to wrong population group (patients without pleural effusion) [38], or unknown number of patients with pleural effusion [15]. ...
The role of PET and integrated PET-CT in the diagnostic workup of suspected malignant pleural effusions is unknown. Earlier systematic reviews (published 2014 and 2015) both included pleural pathology without effusion, and reached contradictory conclusions. Five studies have been published since the latest review. This systematic review and meta-analysis aims to summarise the evidence of PET and integrated PET-CT in predicting pleural malignancy in patients suspected of having malignant pleural effusions.
A meta-analysis based on a systematic literature search in Cochrane Library, Medline, EMBASE and Clinicaltrials.gov was performed. Diagnostic studies evaluating the performance of PET or PET-CT in patients with suspected malignant pleural effusion, using pleural fluid cytology or histopathology as the reference test, and presenting sufficient data for constructing a 2x2 table were included. The quality of the studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 score. Subgroup analyses on image modality, interpretation method and known malignancy status pre index-test application were planned.
Seven studies with low risk of bias were included. The pooled ability to separate benign from malignant effusions varied with image modality, interpretation method and known malignancy status pre index-test application. In studies using PET-CT, visual/qualitative image analysis was superior to semi-quantitative with positive (LR+) and negative likelihood ratio (LR-) of 9.9 (4.5-15.3) respectively 0.1 (0.1-0.2). There was considerable heterogeneity among studies.
In conclusion, visual/qualitative image analysis of integrated PET-CT seems to add relevant information in the work-up of suspected malignant pleural effusions with LR+ and LR- close to rigorous pre-set cut-offs of >10 and <0.1. However, the quality of evidence was low due to inter-study heterogeneity, and inability to assess meta-bias.
... Tumor histology is a key point influencing survival together with tumor stage: epithelioid MPM confers the best prognosis while sarcomatous and mixed histologies are more aggressive, thus being EPP indicated in early stage epithelioid MPM (9,10). ...
... Positron emission tomography (PET) is useful to determine if a patient presents nodal involvement, contralateral disease or-rarely-distant metastasis (10). ...
... Plevrayı etkileyen malign lezyonların çoğu, diffüz malign mezotelyomalardır. FDG'nin malign plevral mezotelyomaların (MPM) tanısında ve ilk evrelemesindeki olumlu katkılarını bildiren pek çok araştırma mevcuttur (30)(31)(32)(33)(34)(35). Son yıllarda bu çalışmaları rekürrens tayininde FDG PET ve FDG PET-BT'nin kullanımını sorgulayan yayınlar takip etmiştir (Şekil 2) (36-38). ...
... Günümüzde kullanılan tedavi yöntemlerindeki gelişmeler sayesinde MPM olguları için beklenen yaşam süresi ve uzak metastazların görülme olasılığı artmıştır. FDG PET ve FDG PET-BT'nin uzak metastazların Şekil 1. Tanı esnasında sol iliak kemikte metastatik lezyon saptanan Küçük Hücreli Olmayan Akciğer Kanseri olgusu saptanmasındaki rolü yine literatürde vurgulanan diğer önemli bir konu olmuştur (30)(31)(32)(33)35). Erasmus ve ark. ...
... This includes determining if a tumor is T3 (resectable) or T4 (unresectable), as well as determining whether a N3 node or distant metastases are present. 18F-FDG PET/CT has been shown to be superior to other imaging modalities in the detection of metastases from malignant pleural mesothelioma (66). Patients who underwent extrapleural pneumonectomy in conjunction with adjuvant chemotherapy and radiation in a study by Sugarbaker et al. ...
... These tumors are well-described in numerous species, including humans and cattle [20][21][22][23][24][25][26]. In veterinary medicine, mesothelioma has been classified into papillary epithelioid, sarcomatoid, and, most commonly, biphasic on the basis of the histological growth pattern [27]. The tumoral cells concern the peritoneum and the pleura and the pericardium exceptionally [28]. ...
Tumors in cows are not frequently reported in the literature. They often represent unusual findings in live animals and are incidental at slaughter with rare positive therapeutic outcomes for farmers. A 9-year-old beef cow was referred to the hospital of ruminants of the National Veterinary School of Toulouse, France. The cow started to become sick 10 days prior, and major symptoms were anorexia, arched back, tachycardia, and tachypnea associated with significantly attenuated cardiac and pulmonary sounds upon right-sided auscultation. After specific investigations, a thoracic sarcoma associated with unilateral empyema was diagnosed. The empyema was treated, and supportive treatment was only performed for the tumor. Although the sarcoma remained, clinical improvement was significant, and the cow went back to her farm of origin. After the end of the withdrawal period, the cow recovered clinically but was culled by the owners for economic reasons. The present case report offers a continuum from the initial clinical signs motivating specific investigations to interesting laboratory findings, which were confirmed post-mortem.
... 3,16,42 This advantage of metabolic imaging with [ 18 F]FDG PET/CT determines also its ability to better stage MPM (Fig. 1), leading to a direct impact on patients management 16 ranging from 20% to 40% of the cases. [43][44][45][46] In fact, various authors have reported a significantly superior diagnostic performance for PET/CT compared to CT alone, [46][47][48] particularly for diffuse chest disease, mediastinal lymph nodes and extra-thoracic localizations, for which the modality shows sensitivities of 100%, 88%, and 100%, respectively ( Table 2). In ...
Malignant mesothelioma is an aggressive tumor originating from the mesothelial cells and presenting in general with a very poor prognosis. The pleural localization represents the prevailing disease site, while peritoneal involvement is commonly rare. The WHO classifies mesotheliomas into epithelioid, biphasic, and sarcomatoid histotypes, having diverse outcome with the sarcomatoid or biphasic forms showing the poorest prognosis. Given the peculiar rind-like pattern of growth, mesothelioma assessment is rather challenging for medical imagers. Conventional imaging is principally based on contrast-enhanced CT, while the role of functional and metabolic imaging is regarded as complementary. By focusing essentially on the staging and restaging role of [18F]FDG PET/CT in malignant mesotheliomas, the present review will summarize the available data present in literature and provide some hints on alternative imaging and future perspectives. Given the prevailing incidence of pleural disease, the majority of the information will be addressed on malignant pleural mesothelioma, although a summary of principal characteristics and imaging findings in patients with peritoneal mesothelioma will be also provided.
... For MPM diagnosis, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings, which often include unilateral circumferential or near-circumferential pleural and fissural thickening indicating FDG avidity, are generally utilized. In fact, several groups have reported use of visual analysis or semiquantitative measurements (maximum standardized uptake value; SUVmax) to demonstrate the clinical utility of FDG-PET and PET/CT for discriminating MPM from inflammatory conditions and benign pleural tumors, with sensitivity, specificity, accuracy in those reports ranging from 60-100%, 62-100%, and 84-98%, respectively [4][5][6][7][8][9][10]. In a meta-analysis of 407 patients with MPM and 232 with benign pleural conditions, FDG-PET/CT findings were used for differentiation of MPM from benign pleural disease, with pooled sensitivity and specificity found to be 81% and 74%, respectively, and an area under the receiver operating characteristic (ROC) curve value of 0.838 [11]. ...
Objectives:
This study analyzed an artificial intelligence (AI) deep learning method with a three-dimensional deep convolutional neural network (3D DCNN) in regard to diagnostic accuracy to differentiate malignant pleural mesothelioma (MPM) from benign pleural disease using FDG-PET/CT results.
Results:
For protocol A, the area under the ROC curve (AUC)/sensitivity/specificity/accuracy values were 0.825/77.9% (81/104)/76.4% (55/72)/77.3% (136/176), while those for protocol B were 0.854/80.8% (84/104)/77.8% (56/72)/79.5% (140/176), for protocol C were 0.881/85.6% (89/104)/75.0% (54/72)/81.3% (143/176), and for protocol D were 0.896/88.5% (92/104)/73.6% (53/72)/82.4% (145/176). Protocol D showed significantly better diagnostic performance as compared to A, B, and C in ROC analysis (p = 0.031, p = 0.0020, p = 0.041, respectively).
Materials and methods:
Eight hundred seventy-five consecutive patients with histologically proven or suspected MPM, shown by history, physical examination findings, and chest CT results, who underwent FDG-PET/CT examinations between 2007 and 2017 were investigated in a retrospective manner. There were 525 patients (314 MPM, 211 benign pleural disease) in the deep learning training set, 174 (102 MPM, 72 benign pleural disease) in the validation set, and 176 (104 MPM, 72 benign pleural disease) in the test set. Using AI with PET/CT alone (protocol A), human visual reading (protocol B), a quantitative method that incorporated maximum standardized uptake value (SUVmax) (protocol C), and a combination of PET/CT, SUVmax, gender, and age (protocol D), obtained data were subjected to ROC curve analyses.
Conclusions:
Deep learning with 3D DCNN in combination with FDG-PET/CT imaging results as well as clinical features comprise a novel potential tool shows flexibility for differential diagnosis of MPM.
... The prognostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/ CT) imaging in MPM patients is well known: high FDG uptake is usually associated with a poor prognosis [12] and FDG PET/CT shows high sensitivity and specificity in the detection of MPM [13,14]. The use of FDG PET/CT in defining the target volume in RT of MPM has not been discussed even in the most recent papers [15], although some studies have shown the value of PET in the diagnosis [16,17] and prognosis [18,19] of MPM. Recent studies have shown that FDG PET allows patient stratification for surgical treatment [20] and early prediction of chemotherapy response and survival [21]. ...
Purpose:
The value of FDG PET-derived parameters in predicting overall survival (OS), local relapse-free survival (LRFS) and distant relapse-free survival (DRFS) in treated patients with malignant pleural mesothelioma (MPM) was evaluated.
Methods:
This retrospective evaluation included 55 MPM patients treated between March 2006 and February 2015 with FDG PET/CT-guided salvage helical tomotherapy (HTT) after previous surgery plus chemotherapy. Univariate Cox regression analysis was performed to assess the impact of the following FDG PET-derived parameters: biological target volume (BTV), mean and maximum standardized uptake values (SUVmean/max), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured using different uptake thresholds (40%, 50% and 60%). Logistic regression was then performed to identify the best FDG PET-derived parameters for selecting patients with poorer survival.
Results:
The median OS was 9.1 months (range 0.0 - 69.6 months) after the end of HTT; 54/55 patients were dead at the last follow-up. BTV and TLG40, TLG50 and TLG60 were the most significant predictors of OS (p < 0.005). The median OS was 4.8 months in patients with MTV60 >5 cm3 and TLG40 >334.4, compared with 13.8 months and 16.1 months in patients with smaller values, respectively. The median LRFS and DRFS were 6.2 months (range 1.2 - 39.4 months) and 6.5 months (0.0 - 66.4 months), respectively. TLG40, TLG50 and TLG60 were significantly correlated with LRFS (p < 0.015). Median DRFS was 6.4 months in patients with MTV40 >39.6 cm3 and 6.2 months in patients with TLG40 >334.4, compared with 17 months and 18.8 months in patients with smaller values. BTV, TLG40 and MTV40 were also found to be good predictors in patients with poor OS/LRFS/DRFS (median survival times less than the median values).
Conclusion:
FDG PET-derived parameters effectively discriminated patients with a poor prognosis and may be helpful in the selection of MPM patients for salvage HTT.
... Findings have not been univocal, since diagnostic performance has shown a large range between different authors. Gerbaudo et al 84 reported an overall accuracy of 94% (sensitivity 97%, specificity 80%). Agreement with tumor biopsy was very high (94%, k=0.77), better than with CT (82%, k=0.47; ...
Malignant pleural mesothelioma (MPM) is a disease with limited therapeutic options, the management of which is still controversial. Diagnosis is usually made by thoracoscopy, which allows multiple biopsies with histological subtyping and is indicated for staging purposes in surgical candidates. The recommended and recently updated classification for clinical use is the TNM staging system established by the International Mesothelioma Interest Group and the International Association for the Study of Lung Cancer, which is based mainly on surgical and pathological variables, as well as on cross-sectional imaging. Contrast-enhanced computed tomography is the primary imaging procedure. Currently, the most used measurement system for MPM is the modified Response Evaluation Criteria in Solid Tumors (RECIST) method, which is based on unidimensional measurements of tumor thickness perpendicular to the chest wall or mediastinum. Magnetic resonance imaging and functional imaging with (18)F-fluoro-2-deoxy-D-glucose positron-emission tomography can provide additional staging information in selected cases, although the usefulness of this method is limited in patients undergoing pleurodesis. Molecular reclassification of MPM and gene expression or miRNA prognostic models have the potential to improve prognostication and patient selection for a proper treatment algorithm; however, they await prospective validation to be introduced in clinical practice.
... FDG-PET is an effective modality for identifying patients who may have metastasis to lymph nodes or extrathoracic sites (28)(29)(30)(31). In particular, integrated PET-CT has been found to provide modest improvement to staging accuracy relative to CT, particularly for detection of T4 (32). ...
Malignant pleural mesothelioma remains a rapidly fatal cancer with few effective therapies. Unusual anatomic features complicate determination of stage and prognosis for individual patients. Validation of staging criteria has been difficult given the rarity of the disease and the fact that only a minority of patients undergo surgical resection with pathological examination of their tumors. Thus, additional heuristic factors and algorithms have been taken into account by clinicians to estimate prognosis and inform discussion of appropriate management strategies or clinical research protocols with patients.
... PET/CT findings in malignant mesothelioma are commonly of unilateral circumferential pleural uptake. FDG PET has been shown to have sensitivity of 95-97 % and specificity of 78-92 % for the evaluation of primary MPM [8][9][10][11][12][13]. PET/CT is superior to other imaging modalities for evaluation of distant metastatic disease of MPM given its whole-body capability. ...
Malignant pleural mesothelioma (MPM) is a tumor of mesodermal origin that arises from the serosa of the pleura, peritoneum, pericardium or tunica vaginalis. MPM is well known to have a poor prognosis with a median survival time of 12 months. Accurate diagnosis, staging and restaging of MPM are crucial with [18F] flurodeoxy-D-glucose positron emission tomography (FDG PET/CT) playing an increasingly important role. Here we report a case of MPM with unusual contiguous soft tissue spread of the tumor along the dermal and fascial planes characterized by PET/CT. Given that the loco-regional tumor in the thorax was under control on PET/CT, the death of the patient was most likely associated with physiologic or metabolic causes associated with an extra-thoracic tumor.
... PET/CT findings in MPM commonly include unilateral circumferential or near-circumferential pleural and fissural thickening that shows 18 F-FDG avidity (Figs. 1, 2, 3). Using a visual analysis or semiquantitative measurements (maximum standardized uptake value [SUV max ]), many groups have demonstrated the clinical utility of 18 F-FDG PET and PET/CT for discriminating MPM from inflammatory conditions and benign pleural tumors with a sensitivity of 60-100 %, specificity of 78-100 %, and accuracy of 91-98 % [14][15][16][17][18][19][20][21][22] (Table 1). Unfortunately, 18 F-FDG PET imaging has poor sensitivity for subcentimeter cancers because of the limited spatial resolution of current PET/CT cameras, which is around 5-6 mm [23]. ...
Positron emission tomography/computed tomography (PET/CT) integrated with 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) has emerged as a powerful tool for combined metabolic and anatomic evaluations in clinical oncologic imaging. This review discusses the utility of 18F-FDG PET/CT as a tool to manage patients with malignant pleural mesothelioma. We discuss different stages of patient management in malignant pleural mesothelioma, including diagnosis, initial staging, therapy planning, early treatment response assessment, re-staging, and prognosis.
... Lymph nodes appeared normal based on CT scans. Another study at Brigham and Women's Hospital and Harvard Medical School in Boston evaluated 15 patients, 11 of whom had MPM and 4 who were disease-free ( Gerbaudo et al., 2002). PET results were compared with laboratory analysis of biopsied fluids and tissues. ...
... The role of FDG-PET/CT in the definition of the target volume in the radiotherapy of MPM is not mentioned even in the most recent papers [22], although some publications have shown that PET could play an important role in MPM diagnosis [4,16] and its prognostic value has been demonstrated [5,33]. Recent studies have shown that FDG-PET allows the stratification of the patients for surgical treatment [14,37] and permits the early prediction of chemotherapy response and survival [15]. ...
To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM).
A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV).
Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p=0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p=0.003).
The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection.
Background and objectives:
The results of previous PET-CT studies are contradictory for discriminating malignant from benign pleural effusions. We purpose to develop a PET-CT score for differentiating between benign and malignant effusions.
Patients and methods:
We conducted a prospective study of consecutive patients with pleural effusions undergoing PET-CT from October 2013 to October 2019 (referral cohort). PET-CT scan features evaluated using the SUV were: linear thickening; nodular thickening; nodules; masses; circumferential thickening; mediastinal and fissural pleural involvement; intrathoracic lymph nodes; pleural loculation; inflammatory consolidation; pleural calcification; cardiomegaly; pericardial effusion; bilateral effusion; lung mass; liver metastasis and other extra-pleural malignancy. The results were validated in an independent prospective cohort from November 2019 to June 2021.
Results:
One hundred and ninety-nine patients were enrolled in the referral cohort (91 with malignant effusions and 108 benign). The most useful parameters for the development of a PET-CT score were: nodular pleural thickening, pleural nodules with SUV>7.5, lung mass or extra pleural malignancy (10 points each), mammary lymph node with SUV>4.5 (5 points) and cardiomegaly (-1 point). With a cut-off value of >9 points in the referral cohort, the score established the diagnosis of malignant pleural effusion with sensitivity 87.9%, specificity 90.7%, positive predictive value 88.9%, negative predictive value 89.9%, positive likelihood ratio 7.81 and negative likelihood ratio 0.106. These results were validated in an independent prospective cohort of 75 patients.
Conclusions:
PET-CT score was shown to provide relevant information for the identification of malignant pleural effusion.
Neoplasms of the pleura are a diverse group of benign and malignant pathologic entities that include both primary and secondary malignancies. Most neoplasms of the pleura are metastases, typically from lung cancer, although extrathoracic neoplasms such as breast and ovarian cancer have a predilection for spread to the pleura. This chapter discusses the most common primary malignant neoplasm to arise from the pleura, diffuse malignant pleural mesothelioma (MPM), with a comprehensive review of the imaging, staging evaluation, and treatment considerations for MPM.
2-deoxy-2-[¹⁸F]fluoro-D-glucose [¹⁸F]FDG-PET/CT represents the metabolic imaging of choice in various cancer types. Used either at diagnosis or during treatment response assessment, the modality allows for a more accurate definition of tumor extent compared to morphological imaging and is able to predict the therapeutic benefit earlier in time. Due to the aspecific uptake property of [¹⁸F]FDG there is an overlap of its distribution in normal and pathological conditions, which can make the interpretation of the imaging challenging. Lung and pleural neoplasia are no exception to this, thus acknowledging of possible pitfalls and artifacts are mandatory for image interpretation. While most pitfalls and artifacts are common for all indications with metabolic imaging with [¹⁸F]FDG-PET/CT, there are specific variants and pitfalls in lung cancer and malignant pleural mesothelioma. The aim of the present article is to shed light on the most frequent and relevant variants and pitfalls in [¹⁸F]FDG-PET/CT imaging in lung cancer and malignant pleural mesothelioma.
Integrated positron emission tomography/computed tomography (PET/CT) with 2-[¹⁸F]fluoro-2-deoxyd-glucose (¹⁸F-FDG) has emerged as a powerful tool for combined metabolic and anatomic evaluations in clinical oncologic imaging. ¹⁸F-FDG PET/CT is also a useful tool to manage patients with malignant pleural mesothelioma, including diagnosis, initial staging, and treatment response assessment. However, a further improvement about PET is desirable.
Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. Unlike many solid cancers in which tumour stage is the most important prognostic factor, the assessment of the extent of tumour in MPM presents unique difficulties in accurate staging due to the anatomical nature of the tumour. The extension of the tumour, described as T factor, correlates with prognosis. Accurate lymph node staging in MPM is crucial as the presence of lymph node metastases adversely affects outcome. The eighth TNM staging system is the most recent and updated staging system internationally used.
Background:
When locating the sentinel lymph node (SLN), surgeons use state-of-the-art imaging devices, such as a 1D gamma probe or less widely spread a 2D gamma camera. These devices project the 3D subspace onto a 1D respectively 2D space, hence loosing accuracy and the depth of the SLN which is very important, especially in the head and neck area with many critical structures in close vicinity. Recent methods which use a multi-pinhole collimator and a single gamma detector image try to gain a depth estimation of the SLN. The low intensity of the sources together with the computational cost of the optimization process make the reconstruction in real-time, however, very challenging.
Results:
In this paper, we use an optimal design approach to improve the classical pinhole design, resulting in a non-symmetric distribution of the pinholes of the collimator. This new design shows a great improvement of the accuracy when reconstructing the position and depth of the radioactive tracer. Then, we introduce our Sentinel lymph node fingerprinting (SLNF) algorithm, inspired by MR-fingerprinting, for fast and accurate reconstruction of the tracer distribution in 3D space using a single gamma detector image. As a further advantage, the method requires no pre-processing, i.e. filtering of the detector image. The method is very stable in its performance even for low exposure times. In our ex vivo experiments, we successfully located multiple Technetium 99m (Tc-99m) sources with an exposure time of only one second and still, with a very small L 2-error.
Conclusion:
These promising results under short exposure time are very encouraging for SLN biopsy. Although, this device has not been tested on patients yet, we believe: that this approach will give the surgeon accurate 3D positions of the SLN and hence, can potentially reduce the trauma for the patient.
Lungenkarzinome stehen bei den bosartigen Tumorerkrankungen weltweit an erster Stelle. Nach letzten Schatzungen gab es 2009 weltweit 1,6 Millionen Erkrankungen [42] und 1,3 Millionen Todesfalle. In der onkologischen Sterbestatistik nimmt diese Entitat bei Mannern den ersten und Frauen den dritten Platz ein. Die Zahl der Neuerkrankungen betrug nach den Daten des Robert-Koch-Instituts im Jahr 2010 allein in Deutschland fur Manner 35.040 und fur Frauen 17.030, die Sterbefalle lagen jeweils bei 29.381/13.627. Die relative 5-Jahres-Uberlebenszeit betrug bei Männern 16 %. In der langjahrigen Entwicklung gingen die Raten bei den Mannern seit den 90er Jahren um 20 %. Hauptgrund ist der geanderte Nikotinkonsum.
Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm arising mainly in the pleural and with tendency to invasion to adjacent structures, such as chest wall, mediastinum and diaphragm. Lymph node metastasis and extension to other organs also can occur. Management is extremely difficult with a described median survival period of 9 to 17 months. Neoplastic extension and VEGF expression have direct relationship to prognosis.
Although computed tomography is the primary imaging modality for diagnosis, staging and follow – up of therapeutic response to MPM, functional techniques such as diffusion weighted imaging (DWI), dynamic contrast enhanced MR imaging (DCE – MRI), and 2-deoxy-2-[18F]fluoro-D-glucose-(FDG)-positron emission tomography-computed tomography (18FDG-PET/CT) allow better differentiation of benign versus malignant pleural disease, assessment of local infiltration of adjacent structures, whole body extension and monitoring therapeutic response. Because the importance of accurate staging, cell type and neoangiogenesis in the prognosis of this kind of tumors, some DWI, DCE and 18FDG-PET/CT related parameters have been related directly to good or poor outcome previous to applying antiangiogenic agents.
Functional MRI (DCE-MRI and DWI) and 18FDG-PET/CT have the potential to provide valuable information in the characterization of primary and metastatic chest wall tumors, but also in the differentiation of benign of malignant ones and therapeutic response monitorization.
In the next few lines we are going to review different aspects of MPM with special focus on functional techniques and its role in staging and assessment of therapeutic response and recurrence. Also functional imaging of other benign and malignant (non-MPM) diseases, which could be false positives, and chest wall tumors are discussed.
Positron emission tomography (PET) is a noninvasive medical imaging technology that can generate high-resolution images of human and animal physiological functions. It is used for a variety of clinical applications in oncology, neurology, and cardiology, but the principal clinical application of PET is in oncology, where it is used to locate malignant tumors. It can be used not only to detect disease, but also to help in planning its treatment and monitoring the effectiveness of the treatment. The PET camera can detect therapeutic changes earlier than anatomic imaging modalities because the structure being studied must significantly change in size and shape before it is detectable by anatomic imaging devices.
Imaging plays an integral role in the detection, diagnosis, staging, and management of lung and pleural tumors. This chapter presents a general overview of lung and pleural tumor imaging and describes the advantages and limitations of the different imaging modalities, including radiographs, computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI), in the workup of intrathoracic neoplasms. It illustrates the typical radiologic appearances of pulmonary tumors, including features that help distinguish benign entities from primary and secondary lung and pleural cancers, with emphasis on the complementary role of radiology with histologic analysis of tumor tissue. This chapter explains patterns of metastatic disease from primary intrathoracic tumors in addition to lung metastases from extrathoracic neoplasms. The staging systems for primary non-small cell lung cancers (7th edition), small-cell lung cancer, and malignant pleural mesothelioma, as well as the new classification of lung adenocarcinomas, are discussed. The guidelines of the American College of Chest Physicians for imaging utilization in malignancy staging are presented. This chapter intends to guide the reader to the best choice of imaging studies, to appropriately manage patients with intrathoracic tumors for correct selection of patients for potentially curative surgery.
The clinical features of pleural disease are often nonspecific and may require complex imaging and histology for diagnosis. The recent improvements in imaging techniques, from ultrasound through to multislice computed tomography and fluorodeoxy glucose positron emission tomography computed tomography, alongside the increased use of medical thoracoscopy have improved the detection and characterization of pleural disease. This article discusses the use of imaging techniques in patients with pleural disease and correlates imaging features with histology.
One reason for the poor outcomes of multimodality therapies, including macroscopic complete resection, in patients with malignant pleural mesothelioma (MPM) is the difficulty of correctly staging the disease, which can result in incomplete resection. The purpose of this study was to investigate the aspects of tumor infiltration to the port site and the usefulness of preoperative FDG PET/CT for diagnosing MPM.
Between June 2007 and May 2013, 21 patients who underwent surgical treatment with curative intent for MPM that had been previously diagnosed on a video-assisted thoracic surgery (VATS) biopsy were included in this study.
There were 17 males and four females, with a mean age of 63 years. The accumulation of FDG at the port site was observed in all nine patients with tumor infiltration to the port site, whereas this feature was not noted in 15 patients without tumor extension to the port site. There were more positive lymph node cases in the infiltration group than in the non-infiltration group (p = 0.02). No significant differences in survival were observed between the patients with and without tumor infiltration to the port site.
FDG PET/CT is useful for detecting tumor infiltration of MPM to the port site and may help to prevent local recurrence, especially port site relapse, following macroscopic complete resection. However, this condition is related to tumor aggressiveness; therefore, performing careful staging and determining the appropriate treatment strategy are required in such patients.
OBJECTIVE. FDG PET/CT is emerging as an important modality in the evaluation of pleural tumors. PET/CT has an established role in the diagnosis and staging and shows promise in therapy planning, therapy response assessment, and providing prognostic information in patients with malignant pleural mesothelioma. This modality has distinct advantages in characterizing other primary pleural tumors and pleural metastases. CONCLUSION. FDG PET/CT is a useful imaging modality in the management of patients with primary pleural tumors and pleural metastases.
Assessment of response is important to interpret early phase clinical trial results and to guide individual patient management. In malignant pleural mesothelioma (MPM), the circumferential growth pattern of the disease, the presence of pleural effusion and atelectasis, and the common use of pleurodesis make this a challenging task for imaging specialists and clinicians. This article reviews the current evidence for radiological and positron emission tomography (PET) response assessment in MPM, and the pitfalls and challenges in its application. Current research and future directions in radiological and PET response are discussed, including the use of novel radiotracers.
Le cancer primitif du poumon est, dans notre expérience comme dans celle de bien d’autres centres, l’indication la plus fréquente de la TEP au FDG (fluorodésoxyglucose).
Imaging of patients with thoracic malignancy usually requires a multimodality approach. Each of these modalities has its own strengths and weaknesses. CT remains central to the staging and restaging of thoracic malignancies, but has recently been complemented with [18F]-2-fluoro-2-deoxy-D-glucose(FDG)–positron emission tomography (PET) imaging to maximize its potential. Furthermore, because FDG-PET/CT is useful at all stages of the workup and treatment of these patients, this modality has taken hold in the clinical realm for evaluation of patients with thoracic malignancy and is rapidly replacing PET-only imaging. MR imaging is also occasionally used in some patients with thoracic malignancies to improve disease staging or lesion characterization. PET/MR imaging may come to be used to evaluate patients with thoracic malignancies as well.
Radiologic imaging of malignancy has evolved over the past 20 years. It not only provides better detection with superior anatomic
resolution through computed tomography (CT) and magnetic resonance (MR) imaging, but it also provides physiologic information
through positron emission tomography (PET). Today’s technology incorporates the use of image modality fusion for even better
disease localization and characterization. By fusing data from PET and CT studies, radiologic imaging brings together the
superior resolution of CT with the low resolution of PET, thereby providing important information on tumor metabolism and
replication. Tumor imaging is at the forefront of this technology explosion and is the focus of most cutting-edge research,
as well as clinical applications. This chapter reviews current imaging of primary and metastatic malignancies of the thorax.
Diffuse malignant pleural mesothelioma (MPM) is an aggressive tumor with dismal prognosis that has largely been associated
with exposure to asbestos. As a disease of industrialized nations predominantly, it is expected to have its peak incidence
around year 2020. In the United States alone, 2500 to 3000 new cases of MPM are diagnosed annually and its incidence is increasing.
Based on a 20- to 50-year latency period between exposure and disease manifestation, there might still be another surge in
incidence in the mid 21st century associated with asbestos exposure from the unfortunate events of September 11, 2001, at
the World Trade Center in New York City. Despite important advances in our understanding of this disease, long-term survivors
are rare due to delay in diagnosis and rapid disease progression. Malignant pleural mesothelioma poses a significant healthcare
problem not only for patients and their caregivers, but also for industry and government in terms of the enormous cost of
compensation.
Epidemiologie. Weltweit werden jährlich 1,3 Mio. Neuerkrankungen verzeichnet, die Tendenz ist steigend1. Bei Männern macht das BC 22% aller Karzinome aus, bei Frauen kommt es mit 8% gleich hinter dem Mammakarzinom. Der Anteil
des NSCLC (“non-small-cell lung cancer, nichtkleinzelliges Bronchialkarzinom) beträgt 80% an den Bronchialkarzinomen und 18%
an allen Karzinomen; das kleinzellige hält einen Anteil von 20–25%. Jährlich sterben 45.000 Menschen am Bronchialkarzinom.
Jeder zwanzigste Mann in Deutschland ist betroffen.
Asbestos and some of its properties, such as resistance to heat, has been known to man since 2500 BC, when it was already being used by Finnish potters. The Greeks called it asbestos meaning “inextinguishable,” and this is the name still used today in many languages.The first known patent for asbestos was issued in the United States of America in 1828 covering its use as an insulating material in steam engines. The first asbestos textile factory started production in 1896. After this date, and throughout the twentieth century, a host of applications for asbestos came into general use, and today there are over 3000 known applications.In view of the repercussions of asbestos use on health and its role in the etiology of respiratory disease, the Scientific Committee of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) asked the society's Work Group on Occupational Respiratory Diseases (EROL) to draw up recommendations in order to provide pulmonologists with clear, concise, and up-to-date guidelines on asbestos-related diseases and their diagnosis.It has been a great pleasure for me to coordinate this group of Spanish professionals whose demonstrated competence and knowledge of asbestos-related disease is well known.
Malignant peritoneal mesothelioma is a rare but highly aggressive malignancy. Therefore, it is important to consider the diagnosis in patients with a smoothly thickened peritoneum or peritoneal mass and to recognise the spectrum of imaging findings. We present a patient with pleural and peritoneal localization of malignant mesothelioma.
Malignant pleural mesothelioma (MPM) is an asbestos-related neoplasm that originates in pleural mesothelial cells and progresses locally along the pleura until it encases the lungs and mediastinum, ultimately causing death. Imaging plays a crucial role in diagnosis and optimal management. Computed tomography (CT) continues to be the primary and initial imaging modality. Magnetic resonance imaging (MRI) complements CT scan and is superior in determining chest wall and diaphragmatic invasion. FDG18-PET/CT provides anatamo-metabolic information and is superior to both CT and MRI in overall staging and monitoring response to therapy. This chapter will detail the imaging finding of MPM and role of imaging in guiding management.
This study investigated the diagnostic performance and prognostic value of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in suspected malignant pleural mesothelioma (MPM) recurrence, in the context of patterns and intensity of FDG uptake, histologic type, and treatment algorithm.
Fifty patients with MPM underwent FDG PET/CT for restaging 11 ± 6 months after therapy. Tumor relapse was confirmed by histopathology, and by clinical evolution and subsequent imaging. Progression-free survival was defined as the time between treatment and the earliest clinical evidence of recurrence. Survival after FDG PET/CT was defined as the time between the scan and death or last follow-up. Overall survival was defined as the time between initial treatment and death or last follow-up date.
Treatment failure was confirmed in 42 patients (30 epithelial and 12 non-epithelial MPM). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for FDG PET/CT were 97.6, 75, 94, 86, and 95.3%, respectively. FDG PET/CT evidence of single site of recurrence was observed in the ipsilateral hemithorax in 18 patients (44%), contralaterally in 2 (5%), and in the abdomen in 1 patient (2%). Bilateral thoracic relapse was detected in three patients (7%). Simultaneous recurrence in the ipsilateral hemithorax and abdomen was observed in ten (24%) patients and in seven (17%) in all three cavities. Unsuspected distant metastases were detected in 11 patients (26%). Four patterns of uptake were observed in recurrent disease: focal, linear, mixed (focal/linear), and encasing, with a significant difference between the intensity of uptake in malignant lesions compared to benign post-therapeutic changes. Lesion uptake was lower in patients previously treated with more aggressive therapy and higher in intrathoracic lesions of patients with distant metastases. FDG PET/CT helped in the selection of 12 patients (29%) who benefited from additional previously unplanned treatment at the time of failure. Multivariate analysis showed that histologic type remained the only independent predictor of progression-free survival. Survival after relapse was independently predicted by the pattern of FDG uptake and PET nodal status, and overall survival by the maximum standard uptake value.
FDG PET/CT is an accurate modality to diagnose and to estimate the extent of locoregional and distant MPM recurrence, and it carries independent prognostic value. Once the disease recurs, survival outcomes seem to be independent of histologic type and highly dependent on the intensity of lesion uptake and on the pattern of metabolically active disease in FDG PET/CT. Our observations should be considered limited to patients treated surgically with or without perioperative therapies and should not be extrapolated to those unresectable cases treated with chemotherapy alone.
There have been several endeavors made to investigate the potential role of 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) (and tracers) and PET-computed tomography imaging in various benign disorders, particularly those related to thoracic structures. These various conditions can be broadly categorized into three groups: (a) infectious diseases (mycobacterial, fungal, bacterial infection), (b) active granulomatous disease such as sarcoidosis, and (c) other non-infectious/inflammatory conditions or proliferative disorders (e.g., radiation pneumonitis, post-lung transplant lymphoproliferative disorders, occupational pleuropulmonary complications, and post-surgical conditions), all of which can demonstrate varying degrees of FDG uptake on PET scans based upon the degree of inflammatory activity. This article reviews the current state of this very important application of FDG-PET imaging.
The diagnosis of malignant mesothelioma is a challenging medical problem. CT often cannot differentiate between benign diffuse pleural thickening and malignant mesothelioma, while thoracentesis and CT-guided biopsies are insensitive. We have assessed the value of positron emission tomography (PET) with 2-fluoro-2-deoxy-D-glucose (FDG) in the evaluation of malignant mesothelioma.
Twenty-eight consecutive patients referred for the evaluation of suspected malignant mesothelioma were evaluated by FDG-PET imaging. Measured attenuation correction was performed in 26 of 28 cases for quantitation with the standardized uptake value (SUV) method. The results of PET imaging were compared with those of video-assisted thoracoscopy or surgical biopsies.
Surgical biopsy specimens confirmed the presence of malignant disease in 24 patients and demonstrated benign processes in the remaining four. The uptake of FDG was significantly higher in malignant than in benign lesions (SUV=4.9+/-2.9 and SUV=1.4+/-0.6, respectively; p<0.0001). With a SUV cutoff of 2.0 to differentiate between malignant and benign disease, a sensitivity of 91% and a specificity of 100% could be achieved, although the activity in some epithelial mesotheliomas tended to be close to this threshold. FDG-PET images provided excellent delineation of the active tumor sites. Hypermetabolic lymph node involvement was noted on FDG-PET images in 12 patients, 9 of which appeared normal on CT scans. Histologic examination in six patients confirmed malignant nodal disease in five cases and indicated granulomatous lymphadenitis in one.
In this highly selected population, FDG-PET imaging was a sensitive method to identify malignant mesothelioma and determine the extent of the disease process.
Objective: The authors examine the feasibility and efficacy of trimodality therapy in the treatment of malignant pleural mesothelioma and identify prognostic factors. Background: Mesothelioma is a rare, uniformly fatal disease that has increased in incidence in recent decades. Single and bimodality therapies do not improve survival. Methods: From 1980 to 1995, 120 patients underwent treatment for pathologically confirmed malignant mesothelioma at Brigham and Women's Hospital and Dana-Farber Cancer Institute (Boston, MA). Initial patient evaluation was performed by a multimodality team. Patients meeting selection criteria and with resectable disease identified by computed tomography scan or magnetic resonance imaging underwent extrapleural pneumonectomy followed by combination chemotherapy and radiotherapy. Results: The cohort included 27 women and 93 men with a mean age of 56 years. Operative mortality rate was 5.0%, with a major morbidity rate of 22%. Overall survival rates were 45% at 2 years and 22% at 5 years. Two and 5-year survival rates were 65% and 27%, respectively, for patients with epithelial cell type, and 20% and 0%, respectively, for patients with sarcomatous or mixed histology tumors. Nodal involvement was a significant negative prognostic factor. Patients who were node negative with epithelial histology had 2- and 5-year survival rates of 74% and 39%, respectively. Involvement of margins at time of resection did not affect survival, except in the case of full-thickness, transdiaphragmatic invasion. Classification on the basis of a revised staging system stratified median survivals, which were 22, 17, and 11 months for stages I, II, and III, respectively (p = 0.04). Conclusions: Extrapleural pneumonectomy with adjuvant therapy is appropriate treatment for selected patients with malignant mesothelioma selected using a revised staging system.
Mesothelioma incidence rates based on data from population-based cancer registries in New York State (exclusive of New York City), Los Angeles County, California, and the SEER Program of the National Cancer Institute were analyzed for trends, using original cancer registry diagnoses. Results indicate a significant increase in incidence during 1973-80 for pleural mesothelioma among white males older than 55 at time of diagnosis but not for other age-race-sex-site subgroups. A histopathologic review of New York State and Los Angeles County cases by two independent pathologists, expert in the diagnosis of mesothelioma, lowered the overall estimates but a significant upward trend remained. The observed trend does not appear to be related to changes in diagnostic practice. The results of a five-member panel of expert pathologists will be published in a separate methodology paper.
Fluorine-18 deoxyglucose (FDG) is not a very tumour-specific substance, and its accumulation in benign lesions with increased glucose metabolism may give rise to false-positive results and hence cause FDG positron emission tomography (PET) to display relatively low specificity (frequently below 85%). Correct interpretation of FDG PET studies is predicated upon detailed knowledge of morphological abnormalities, and the importance of the correlation of functional and morphological information, as derived from computed tomography or magnetic resonance imaging, is discussed. It is emphasized that image fusion programs cannot substitute for understanding of functional and morphological methods. The reconstruction of PET cross-sections is considered, and it is concluded that an iterative image reconstruction method is to be favoured, given its advantages in reducing image artefacts and improving quantification of radioactivity concentrations. The differentiation of malignant and benign lesions when using FDG PET is then reviewed; false-positive findings may be obtained, for example, in patients with acute inflammatory lesions, chronic pancreatitis, retroperitoneal fibrosis or salivary gland tumours. It is suggested that these problems may be alleviated by means of multitracer studies, e.g. using carbon-11 labelled aminoisobutyric acid for quantification of A-type amino acid transport. Finally, the effects of radiotherapy and chemotherapy on FDG uptake and the problems that accrue from these effects are reviewed. Both radiotherapy and chemotherapy can cause increased FDG uptake, complicating diagnosis and evaluation. Knowledge of the effects of different treatment procedures on regional FDG metabolism is therefore necessary for correct interpretation of the PET data.
Diffuse malignant pleural mesothelioma, a rare disease, is characterized by an aggressive local behavior and scant response to therapy. The first series using single modality therapy showed failure in terms of survival and local control. More recently, multimodality therapy has been used against this disease with better results, but still with more room for substantial improvement. The current multimodality series reported are isolated, single-institutional experiences with different treatment schemes, using different staging systems, most of which have not been validated. There is an enormous need for multiinstitutional prospective trials to evaluate the current treatment schemes in light of the steady increase in the incidence of this lethal tumor. The trimodality therapy used at the Brigham and Women's Hospital for selected patients is described.
An accurate diagnosis is essential to a rational approach to the treatment of diffuse malignant pleural mesothelioma and generally requires pathological examination with the application of special techniques. In recent years, immunohistochemistry has greatly abetted the distinction of mesothelioma from its many morphological mimics, yet diagnostic difficulties still remain because reactive hyperplasias and diverse tumors closely mimic mesothelioma. Mesotheliomas are classified into epithelial, mixed, sarcomatoid and undifferentiated types, based on conventional histological examination. The classification provides important prognostic information. Furthermore, differential diagnosis is directly related to histological type. Although such special techniques as histochemistry and electron microscopy continue to play an important role in some cases, immunohistochemistry often has replaced these in distinguishing epithelial-type mesothelioma from metastatic adenocarcinoma. It is also helpful in distinguishing sarcomatoid mesothelioma from it numerous morphological mimics. The distinction of mesothelioma from reactive mesothelial proliferations is still based on morphological examination and may be quite problematic. Recent cytogenetic studies, which have identified characteristic clonal deletions in mesotheliomas, give promise of providing valuable assistance in this distinction in the future.
Our aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma.
From 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy.
Forty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P =.0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P =.02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P =.004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P <.0001), positive resection margins (OR 1.7, CI 1.2-2.6; P =.0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2; P =.0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P =.013). A previously published staging system using these variables stratified survival (P <.05).
(1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival.
The diagnostic approach to pleural diseases may be difficult. The CT scan, which is the current diagnostic technique, has limited accuracy both in the differentiation between benign and malignant pleural diseases and in the diagnosis of primary and metastatic pleural neoplasms. Invasive procedures, such as thoracoscopy, are therefore frequently required to complete the diagnostic approach. The increasing incidence of malignant pleural mesothelioma has led to the development of new treatment strategies, which still need to be fully validated. There is, therefore, a need for new diagnostic techniques that can lead to a definite diagnosis and a satisfactory evaluation of the response to treatment. Encouraging results have been reported with the F-18-labeled analogue of 2-deoxyglucose (18-FDG) positron emission tomography (PET) in the evaluation of chest tumors such as lung cancer. The aim of this study was to evaluate the role of 18-FDG PET in the diagnostic assessment of pleural diseases.
Patients with CT scan evidence of pleural thickening, or fluid, entered a study to evaluate the accuracy of 18-FDG PET in diagnosing pleural diseases. Image analysis was performed both with visual interpretation and using a semiquantitative method, standardized uptake values (SUV), on coronal, sagittal and axial reconstructions. The results of PET imaging were compared to histological data. PET was also performed before and after treatment in patients who underwent chemotherapy to evaluate the accuracy of this technique in the assessment of the response.
Fourteen patients entered the study. Histology demonstrated a malignant pleural disease in 13 patients; malignant pleural mesothelioma in ten patients, adenocarcinoma in two and liposarcoma in one. Benign pleural disease was diagnosed in the remaining patient. PET assessment demonstrated significant 18-FDG uptake in 12 of the 13 patients with a malignant disease, also revealing distant metastases in two of them. A false-negative result was observed in a patient with an epithelial mesothelioma. The overall accuracy was 92%. A benign pleural disease without significant uptake was correctly diagnosed in another patient. An aspecific uptake was observed in two patients who had undergone pleurectomy and intrapleural chemotherapy. A decreased tracer uptake was observed after chemotherapy in four patients.
These preliminary results demonstrate that 18-FDG PET may have a great potential, both in the differential diagnosis of pleural diseases and in the evaluation of the response to treatment. At present, however, histological thoracoscopic diagnosis remains mandatory before planning treatment. Further studies in larger groups of patients are needed to draw definite conclusions on the role of PET in the assessment of pleural diseases.
The purpose of this study was to evaluate the utility of positron emission tomography with F18-fluorodeoxyglucose in the preoperative evaluation and staging of malignant mesothelioma in patients who were candidates for aggressive combined modality therapy.
Eighteen consecutive patients with biopsy-proven malignant mesothelioma underwent positron emission tomographic scanning. The results of positron emission tomographic imaging were compared with results obtained by computed tomography, mediastinoscopy, thoracoscopy, and pathologic examination of surgical specimens. All patients fasted and received an average of 14.5 +/- 2.7 mCi of F18-fluorodeoxyglucose for positron emission tomographic scanning. Attenuation-corrected whole-body and regional emission images of the chest and upper abdomen were acquired and formatted into transaxial, coronal, and sagittal images.
All primary malignant mesotheliomas accumulated F18-fluorodeoxyglucose, and the mean standardized uptake value was 7. 6 (range, 3.33-14.85; n = 9). There were no false-negative results of positron emission tomography. Identification of occult extrathoracic metastases by positron emission tomography was the basis for excluding two patients from surgical therapy. There were two false-positive results of positron emission tomography: increased F18-fluorodeoxyglucose uptake in the contralateral chest that was negative by thoracoscopic biopsy (n = 1) and increased abdominal F18-fluorodeoxyglucose uptake after partial colectomy for diverticular disease (n = 1).
Positron emission tomography can identify malignant pleural mesothelioma and appears to be a useful noninvasive staging modality for patients being considered for aggressive combined modality therapy.
The authors define ordered subset processing for standard algorithms (such as expectation maximization, EM) for image restoration from projections. Ordered subsets methods group projection data into an ordered sequence of subsets (or blocks). An iteration of ordered subsets EM is defined as a single pass through all the subsets, in each subset using the current estimate to initialize application of EM with that data subset. This approach is similar in concept to block-Kaczmarz methods introduced by Eggermont et al. (1981) for iterative reconstruction. Simultaneous iterative reconstruction (SIRT) and multiplicative algebraic reconstruction (MART) techniques are well known special cases. Ordered subsets EM (OS-EM) provides a restoration imposing a natural positivity condition and with close links to the EM algorithm. OS-EM is applicable in both single photon (SPECT) and positron emission tomography (PET). In simulation studies in SPECT, the OS-EM algorithm provides an order-of-magnitude acceleration over EM, with restoration quality maintained.