Computed tomography in the evaluation of malignant pleural mesothelioma—Association of tumor size to a sarcomatoid histology, a more advanced TNM stage and poor survival

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Activin A has previously been associated with cancer cachexia and in vitro resistance to platinum-based chemotherapy. We studied circulating activin A concentrations as well as activin B and their antagonists' follistatin/follistatin-like 3 in presurgical patients with nonesmall-cell lung cancer and malignant pleural mesothelioma. We found that circulating activing A levels were elevated in malignant pleural mesothelioma and associated with cancer cachexia and poor response to platinum-based chemotherapy. Circulating activing A separated nonesmall-cell lung cancer from benign lung lesion. Background: Previous preclinical studies have shown that activin A is overexpressed in malignant pleural mesothelioma (MPM), associates with cancer cachexia, and is observed in in vitro resistance to platinum-based chemotherapy. We evaluated circulating activin levels and their endogenous antagonists' follistatin/follistatin-like 3 in intrathoracic tumors. Materials and Methods: Patients suspected of thoracic malignancy were recruited prior to surgery. Serum samples were collected from 21 patients with MPM, 59 patients with nonesmall-cell lung cancer (NSCLC), and 22 patients with benign lung lesions. Circulating activin/follistatin levels were measured using enzymelinked immunosorbent assay and compared with clinicopathologic parameters. Results: Circulating activin A levels were elevated in patients with MPM when compared with patients with NSCLC or benign lung lesion samples (P < .0001). Also, follistatin and follistatin-like 3 levels were the highest in MPM, although with less difference compared with activin A. Receiver operating characteristic analysis for activin A for separating NSCLC from benign lung lesion showed an area under the curve of 0.856 (95% confidence interval, 0.77-0.94). Activin A levels were higher in patients with cachexia (P < .001). In patients with MPM, activin A levels correlated positively with computed tomographybased baseline tumor size (R ¼ 0.549; P ¼ .010) and the change in tumor size after chemotherapy (R ¼ 0.743; P ¼ .0006). Patients with partial response or stable disease had lower circulating activin A levels than the ones with progressive disease (P ¼ .028). Conclusion: Activin A serum level could be used as a biomarker in differentiating malignant and benign lung tumors. Circulating activin A levels were elevated in MPM and associates with cancer cachexia and reduced chemotherapy response.

Section: Discussionmentioning

confidence: 83%

“…The tumor size (TS) was approximated using our previously published method, where the maximal tumor thickness on axial images is multiplied by the tumor extent. 20 The radiologic response to chemotherapy was evaluated using change in TS.…”

Section: Study Design and Populationmentioning

confidence: 99%

Elevated Circulating Activin A Levels in Patients With Malignant Pleural Mesothelioma Are Related to Cancer Cachexia and Reduced Response to Platinum-based Chemotherapy

Paajanen

Ilonen

Lauri

et al. 2020

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“…37 We confirmed our previous finding that tumor size approximation with tumor thickness and extension was a better prognostic factor than CT stage. 16 The optimal treatment regimen remains controversial in MPM since only the benefit from combination chemotherapy has been established in prospective controlled clinical trials. 38 Although we found that surgery and chemotherapy were associated with longer survival, the effects of these treatment modalities on survival could be confounded by patient-driven factors in a nonrandomized setting.…”

Section: Discussionmentioning

confidence: 99%

“…with special experience in occupational radiology, and the mesothelioma size was estimated using a method where the maximal tumor thickness on axial images is multiplied by the tumor extent grade. 16 Pleural plaques were searched from both sides separately and then reported overall as being present or absent. The maximal thickness of pleural effusion was measured on axial planes.…”

Section: Study Design and Populationmentioning

confidence: 99%

Clinical Features in Patients With Malignant Pleural Mesothelioma With 5-Year Survival and Evaluation of Original Diagnoses

Paajanen

Laaksonen

Ilonen

et al. 2020

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Introduction: Malignant pleural mesothelioma (MPM) is a fatal malignancy strongly associated with previous asbestos exposure. Overall survival remains dismal partly due to poor response to available treatment. Aims of this study were to evaluate diagnostic accuracy in a group of MPM patients with an unusually long survival time and to assess the factors related to this prolonged survival.Materials and Methods: Forty-three patients with overall survival exceeding 5 years were accepted to the long-term survivor (LTS) group, and these patients were compared with 84 epithelial MPM patients.Data were collected from various national registers and electronic medical records. In addition, all available histopathological diagnostic samples and computed tomography studies were re-evaluated by experienced specialists.Results: Our study showed a good diagnostic accuracy, with only one patient (0.5%) having an incorrect MPM diagnosis. Two localized malignant mesotheliomas (0.9%) and two well-differentiated papillary mesotheliomas (0.9%) were also found. LTS patients were younger, more frequently females, had a better performance status at time of diagnosis, and had less evidence of prior asbestos exposure. In multivariate analysis, we showed tumor size, Eastern Cooperative Oncology Group performance status, and first-line treatment (both surgery and chemotherapy) to be associated with survival time. Conclusion:We confirmed the diagnosis of MPM in an overwhelming majority of patients in the LTS group. An epithelial subtype of MPM behaving clinically more indolently seems to exist, but further tumor and genetic characterization is needed. The prolonged survival time is most likely explained by a combination of tumor-, patient-, and treatment-related factors.

“…In accordance with our results, in their analysis the estimation of T was a better prognostic factor than TNM stage and was related to the sarcomatoid histology and TNM stages; moreover, the prognostic role of tumor extension was higher than that of tumor thickness. 26 Regarding the comparison with stage, we found that the combinations of TV groups and NPS groups had higher HRs than stage. These results are in line with other studies.…”

Section: Discussionmentioning

confidence: 82%

The Prognostic Role of TNM Staging Compared With Tumor Volume and Number of Pleural Sites in Malignant Pleural Mesothelioma

Proto

Signorelli

Mallone

et al. 2019

Malignant pleural mesothelioma (MPM) is an aggressive disease with a unique morphology and distribution. Because of its peculiar growth pattern, clinical staging is difficult. Quantitative assessment such as tumor volume (TV) was suggested as an alternative prognostic evaluation. In this study we aimed to compare the prognostic role of Tumor, Node, Metastases (TNM) clinical staging with that of alternative staging approaches on the basis of the use of 2 quantitative clinical parameters, TV and number of pleural sites (NPS), in MPM patients (pts). Our data confirmed the prognostic role of TNM, tumor size, TV, and NPS. However, the TV and NPS combination performed better than TV, NPS, and TNM alone as prognostic classifier. Considering different quantitative parameters and translating such an approach from research level to clinical practice could increase prognostic accuracy for MPM pts, and help clinicians choose the best therapeutic strategy. Background: Age, sex, stage, histotype, and surgery are the most recognized prognostic factors for malignant pleural mesothelioma (MPM). Tumor volume (TV) was suggested as an alternative prognostic evaluation. We aimed to assess the prognostic role of Tumor, Node, Metastases (TNM) versus TV and number of pleural sites (NPS). Patients and Methods: Information on stage, TV, and NPS was collected for 52 MPM patients (pts) at our institution from 2009 to 2012. Baseline computed tomography imaging was performed to define TNM, TV, and NPS. Pts were divided in 3 stage groups: early (I-II), III, and IV. A dedicated computer system calculated TV. Pts were divided in 2 groups according to mean baseline TV (483 cm 3 ). NPS was defined on the basis of the NPS macroscopically involved by disease (1-3). The association between TNM, tumor size (T), TV, NPS, TV and NPS, and overall survival was assessed using Cox models adjusted for age, sex, histology, and treatment. Results: Most pts were male; mean age was 62 years. We showed an association between TV, TNM, and T.