Gerbaudo VH, Mamede M, Trotman-Dickenson B, Hatabu H, Sugarbaker DJ.

Division of Nuclear Medicine and Molecular Imaging, Brigham & Women’s Hospital, Harvard Medical School, 75 Francis St., Boston, MA, 02115, USA, vgerbaudo@partners.org.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords FDG, FDG PET/CT, Mesothelioma, Lung cancer, Response to treatment, Recurrence, Survival

Kimura T, Koyama K, Kudoh S, Kawabe J, Yoshimura N, Mitsuoka S, Shiomi S, Hirata K.

Department of Respiratory Medicine, Osaka City University, Osaka. kimutats@med.osaka-cu.ac.jp

Abstract

We report a 56-year-old man who underwent monitoring of the response to chemotherapy of malignant pleural mesothelioma (MPM). ⁸F-fluoro-2-deoxy-_D-glucose positron emission tomography (FDG-PET) and computed tomography (CT) were performed prior to chemotherapy and after the first and second courses of chemotherapy. The tumor lesion exhibited shrinkage on CT and a decrease in the standardized uptake value (SUV) max after the first course of chemotherapy, but exhibited size enlargement and an increase in SUV max after the second course of chemotherapy. These findings suggest that results of quantification of metabolic response by FDG-PET are related to the objective response as determined by CT in patients with MPM.

Keywords: FDG-PET, mesothelioma, SUV, response

Saito Y, Furukawa T, Arano Y, Fujibayashi Y, Saga T.

Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555, Japan.

Abstract

Introduction: Various techniques are available for in vivo imaging, and precise understanding of their characteristics is essential for effective use of the imaging results. We established human mesothelioma cell lines expressing red fluorescent protein (RFP) and examined their fluorescence intensity and uptake of positron emission tomography (PET) tracer analogs to compare their characteristics and assess their usefulness in the evaluation of therapeutics.

Method: A human mesothelioma cell line was stably transfected to express RFP. Fluorescence, cell number and protein amount were measured during cell growth and treatment with cytotoxic reagents. In in vivo experiments, RFP-expressing cells were injected subcutaneously or into the pleural cavity of nude mice, and fluorescence images were taken with or without pemetrexed treatment. The uptake of [³H]3′-deoxy-3′-fluorothymidine ([³H]FLT) and [¹⁴C]2-fluoro-2-deoxy-d-glucose ([¹⁴C]FDG) under treatment with the above reagents in vitro and in vivo were examined.

Results: Strong correlation was observed between fluorescence intensity and total cell number with or without cytotoxic treatment. The uptake of [³H]FLT and [¹⁴C]FDG decreased rapidly after the initiation of treatment with actinomycin D or cycloheximide. When treated with pemetrexed, the uptake of [³H]FLT temporarily increased. The cells formed subcutaneous and orthotopic tumors, with fluorescence intensity correlating with tumor volume. The correlation was sustained under pemetrexed treatment. The uptake of [³H]FLT in vivo increased significantly early after pemetrexed treatment.

Conclusion: Fluorescence imaging could be used to semiquantitatively monitor tumor size, whereas PET could be used to monitor tumor response to therapeutic treatments, and especially, FLT might be a good marker of the response to anti-folate chemotherapeutics.

Keywords: Mesothelioma; Mouse tumor model; Fluorescence imaging; PET; FLT

Sørensen JB, Ravn J, Loft A, Brenøe J, Berthelsen AK; Nordic Mesothelioma Group.

Aaseboe U, Billing B, Bjørck T, Brodin O, Brunsvig P, Forsløw U, Frank H, Hansen O, Harving H, Hillerdal G, Jakobsen KD, Johansson A, Ladegaard L, Lindh B, Melgaard P, Mygind N, Månsson T, Palshof T, Sundstrøm S, Sørensen P, Vigander T.

Department of Oncology, Finsen Centre/National University Hospital, Copenhagen, Denmark. jens.benn.soerensen@rh.regionh.dk

Abstract

Objectives: Extrapleural pneumonectomy (EPP) in MPM may be confined with both morbidity and mortality and careful preoperative staging identifying resectable patients is important. Staging is difficult and the accuracy of preoperative CT scan, 18F-FDG PET/CT scan (PET/CT), and mediastinoscopy is unclear. The objectives were to compare these staging techniques to each other and to surgical–pathological findings.

Methods: Patients had epithelial subtype MPM, age ≤70 years, and lung function test allowing pneumonectomy. Preoperative staging after 3–6 courses of induction chemotherapy included conventional CT scan, PET/CT, and mediastinoscopy. Surgical–pathological findings were compared to preoperative findings.

Results: Forty-two consecutive patients were without T4 or M on CT scan. PET/CT showed inoperability in 12 patients (29%) due to T4 (7 patients) and M1 (7 patients). Among 30 patients with subsequent mediastinoscopy, including 10 with N2/N3 on PET/CT, N2 were histologically verified
in 6 (20%). Among 24 resected patients, T4 occurred in 2 patients (8%), and N2 in 4 (17%), all being PET/CT negative. PET/CT accuracy of T4 and N2/N3 compared to combined histological results of mediastinoscopy and EPP showed sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios of 78% and 50%, 100% and 75%, 100% and 50%, 94% and 75%, not applicable and 5.0, and 0.22 and 0.67, respectively.

Conclusions: Non-curative surgery is avoided in 29% out of 42 MPM patients by preoperative PET/CT and in further 14% by mediastinoscopy. Even though both procedures are valuable, there are false negative findings with both, urging for even more accurate staging procedures.

Keywords: Mesothelioma; Staging; PET/CT scan; Mediastinoscopy; Extrapleural pneumonectomy

Plathow C, Staab A, Schmaehl A, Aschoff P, Zuna I, Pfannenberg C, Peter SH, Eschmann S, Klopp M.

Department of Diagnostic Radiology, University of Tuebingen, Tuebingen, Germany. christian.plathow@uniklinik-freiburg.de

Abstract

Objective: To evaluate and compare the role of computed tomography (CT), positron emission tomography (PET), PET/CT, and magnetic resonance imaging (MRI) in the correct staging of patients with limited malignant pleural mesothelioma (MPM).

Materials and Methods: Fifty-four patients with an epithelial MPM (34 men and 20 women) were included in this study. Patients were referred to our department for staging in a predicted resectable state (stage II/III). Within 3 days, PET/CT and MRI was performed in all patients. Images were evaluated by 3 specialists in the field of PET/CT and MRI. The subexaminations of PET/CT, PET, and CT were independently evaluated with respect to tumor stage. Subexaminations were compared with each other, with MRI and PET/CT. N-stage was verified by mediastinoscopy. Afterward, consensus reading was performed.

In 52 patients, surgery served as gold standard. In 2 patients, follow-up control served as gold standard as an inoperable situation with distant metastases was found. Additionally, interobserver variability ([kappa] value) was calculated.

Results: In stage II, accuracy was 0.77 (CT), 0.86 (PET), 0.8 (MRI), 1.0 (PET/CT), and in stage III 0.75, 0.83, 0.9, 1.0. PET/CT was significantly more accurate (P < 0.05) in stages II and III compared with all other techniques. CT and MRI were not able to detect distant metastases in 2 patients, which changed therapy (operable vs. inoperable). Interobserver variability was 0.7, 0.9, 0.8, 1.0 in stage II and 0.9, 0.9, 0.9, 1.0 in stage III.

Conclusion: PET/CT makes it possible to stage patients with limited MPM with high accuracy and low interobserver variability.

Miles SE, Sandrini A, Johnson AR, Yates DH.

Dust Diseases Board Research & Education Unit, Sydney, NSW, Australia. Deborahy88@hotmail.com.

Abstract

Asbestos-related diffuse pleural thickening (DPT), or extensive fibrosis of the visceral pleura secondary to asbestos exposure, is increasingly common due to the large number of workers previously exposed to asbestos. It may coexist with asbestos related pleural plaques but has a distinctly different pathology. The pathogenesis of this condition as distinct from pleural plaques is gradually becoming understood. Generation of reactive oxygen and nitrogen species, profibrotic cytokines and growth factors in response to asbestos is likely to play a role in the formation of a fibrinous intrapleural matrix. Benign asbestos related pleural effusions commonly antedate the development of diffuse pleural thickening. Environmental as well as occupational exposure to asbestos may also result in pleural fibrosis, particularly in geographic areas with naturally occurring asbestiform soil minerals. Pleural disorders may also occur after household exposure. High resolution computed tomography (CT) is more sensitive and specific than chest radiography for the diagnosis of diffuse pleural thickening, and several classification systems for asbestos-related disorders have been devised. Magnetic resonance imaging and fluorodeoxyglucose positron emission tomography (PET) scanning may be useful in distinguishing between DPT and malignant mesothelioma. DPT may be associated with symptoms such as dyspnoea and chest pain. It causes a restrictive defect on lung function and may rarely result in respiratory failure and death. Treatment is primarily supportive.

Hinshaw JL, Pickhardt PJ.

Department of Radiology, University of Wisconsin Medical School, Madison, WI, 53792, USA.

Abstract

Peritoneal carcinomatosis and metastatic involvement of the retroperitoneum are relatively common manifestations of many organ-based malignancies and lymphoproliferative disorders. Primary malignancies of peritoneal and retroperitoneal origin occur much less frequently, and can be difficult to distinguish from metastatic disease. In many cases, a precise diagnosis based on imaging findings alone is not possible. However, the imaging features of these primary tumors, in combination with the clinical and demographic data, can be utilized to narrow the scope of the differential diagnosis. This chapter will present the clinical and imaging features of primary peritoneal and retroperitoneal tumors arising from the various tissue components that comprise the ligaments, mesenteries and connective tissues of these anatomic spaces.

Park EK, Sandrini A, Yates DH, Thomas PS, Creaney J, Robinson BW, Johnson AR.

Research and Education Unit, Dust Diseases Board, Sydney, NSW, Australia.

Abstract

Rationale: Soluble mesothelin related protein (SMRP) is raised in epithelial type malignant mesothelioma (MM), but the utility of SMRP in screening for MM is unknown.

Objectives: We aimed to evaluate SMRP in asbestos exposed subjects.

Methods: 538 subjects were studied. Those with elevated SMRP (≥ 2.5nM) underwent further investigation including positron-emission tomography/computed tomography.

Measurements and Main Results: Mean (± SD) SMRP in healthy subjects exposed to asbestos (n=223) was 0.79 (± 0.45) nM. 15 subjects had elevated SMRP, of whom one had lung cancer which was successfully resected. Another with lung cancer was undetected by SMRP. No subjects were diagnosed with MM. Mean SMRP in healthy subjects was significantly lower than in subjects with PPs (p<0.01).

Conclusions: This is the first large scale prospective study of SMRP for screening for malignancy in asbestos-exposed individuals. A high false positive rate was observed. SMRP seems unlikely to prove useful in screening for MM.

Keywords: soluble mesothelin related protein, mesothelioma, asbestos-related disorders, diagnostic accuracy, screening

Mahmood S, Martinez de Llano SR.

Department of Radiology, Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. smahmood@yahoo.com

Abstract

A 71-year-old man with newly diagnosed malignant mesothelioma was referred for an F-18 FDG PET/CT study to evaluate the extent of disease. PET showed mild FDG uptake in the right chest, corresponding to a lobulated, mass-like right pleural effusion versus thickening involving the entire right pleural space, and some mediastinal involvement, on the accompanying CT scan. In addition, marked FDG uptake was seen in the proximal left humerus, suspicious for an osseous metastasis. The corresponding CT scan findings of cortical thickening and a "Swiss cheese" appearance were most consistent with Paget disease. The intense FDG uptake in an osseous lesion on FDG-PET in our case reminds us of the variable nature of FDG uptake in Paget disease, the possibility of false-positive findings on FDG-PET in patients with cancer, and the usefulness of the fusion techniques in the evaluation of skeletal lesions, with the potential for discriminating between benign Paget disease and other pathologic bone findings.

Ceresoli GL, Castagneto B, Zucali PA, Favaretto A, Mencoboni M, Grossi F, Cortinovis D, Conte GD, Ceribelli A, Bearz A, Salamina S, De Vincenzo F, Cappuzzo F, Marangolo M, Torri V, Santoro A.

1Department of Oncology, Istituto Clinico Humanitas IRCCS, Rozzano, Milano, Italy.

Abstract

The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. In this study, pooled data from two phase II trials of pemetrexed and carboplatin (PC) as first-line therapy were retrospectively analysed for comparisons between age groups. Patients received pemetrexed 500 mg m^-2 and carboplatin AUC 5 mg ml^-1 min^-1 intravenously every 21 days with standard vitamin supplementation. Elderly patients were defined as those >/=70 years old. A total of 178 patients with an ECOG performance status of </=2 were included. Median age was 65 years (range 38-79), with 48 patients >/=70 years (27%). Grade 3-4 haematological toxicity was slightly worse in >/=70 vs <70-year-old patients, with neutropenia observed in 25.0 vs 13.8% (P=0.11), anaemia in 20.8 vs 6.9% (P=0.01) and thrombocytopenia in 14.6 vs 8.5% (P=0.26). Non-haematological toxicity was mild and similar in the two groups. No significant difference was observed in terms of overall disease control (60.4 vs 66.9%, P=0.47), time to progression (7.2 vs 7.5 months, P=0.42) and survival (10.7 vs 13.9 months, P=0.12). Apart from slightly worse haematological toxicity, there was no significant difference in outcome or toxicity between age groups. The PC regimen is effective and well tolerated in selected elderly patients with MPM.

Keywords: malignant pleural mesothelioma; elderly patients; chemotherapy; carboplatin; pemetrexed