Radiological evaluation of malignant pleural mesothelioma - defining distant metastatic disease

Abstract BackgroundMalignant pleural mesothelioma (MPM) is traditionally characterized by local destructive spread of the pleura and surrounding tissues. Patient outcomes in MPM with distant metastatic dissemination are lacking.MethodsIn this retrospective study, we reviewed a cohort of 164 MPM patients referred to a Phase I trials unit, aiming to describe identified metastatic sites, and correlate with clinical outcomes. Results67% of patients were diagnosed with distant metastatic disease with a high incidence of bone (19%), visceral (14%), contralateral lung (35%) and peritoneal metastases (22%). Peritoneal metastases were more likely in epithelioid versus biphasic/ sarcomatoid MPM (p=0.015). Overall survival was 23.8 months with no statistical difference in survival between those with distant metastases and those without.ConclusionsThis report highlights the frequency of distant metastases and encourages further radiological investigations in the presence of symptoms. In particular, given the relatively high incidence of bone metastases, bone imaging should be considered in advanced MPM clinical workflow and trial protocols. The presence of distant metastases does not appear to have prognostic implications under existing treatment paradigms. This cohort of MPM patients gives an indication of patterns of metastatic spread that are likely to become prevalent as prognosis improves with emerging treatment paradigms.

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Radiological evaluation of malignant pleural mesothelioma - defining distant metastatic disease

BMC Cancer ◽

10.1186/s12885-020-07662-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Dearbhaile Catherine Collins ◽

Raghav Sundar ◽

Anastasia Constantidinou ◽

David Dolling ◽

Timothy Anthony Yap ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Metastatic Disease ◽

Distant Metastases ◽

Peritoneal Metastases ◽

Pleural Mesothelioma ◽

Clinical Workflow ◽

Distant Metastatic Disease ◽

High Incidence ◽

Trial Protocols ◽

Metastatic Sites

Abstract Background Malignant pleural mesothelioma (MPM) is traditionally characterized by local destructive spread of the pleura and surrounding tissues. Patient outcomes in MPM with distant metastatic dissemination are lacking. Methods In this retrospective study, we reviewed a cohort of 164 MPM patients referred to a Phase I trials unit, aiming to describe identified metastatic sites, and correlate with clinical outcomes. Results 67% of patients were diagnosed with distant metastatic disease with a high incidence of bone (19%), visceral (14%), contralateral lung (35%) and peritoneal metastases (22%). Peritoneal metastases were more likely in epithelioid versus biphasic/ sarcomatoid MPM (p = 0.015). Overall survival was 23.8 months with no statistical difference in survival between those with distant metastases and those without. Conclusions This report highlights the frequency of distant metastases and encourages further radiological investigations in the presence of symptoms. In particular, given the relatively high incidence of bone metastases, bone imaging should be considered in advanced MPM clinical workflow and trial protocols. The presence of distant metastases does not appear to have prognostic implications under existing treatment paradigms. This cohort of MPM patients gives an indication of patterns of metastatic spread that are likely to become prevalent as prognosis improves with emerging treatment paradigms.

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Radiological evaluation of malignant pleural mesothelioma - defining distant metastatic disease

10.21203/rs.3.rs-33715/v3 ◽

2020 ◽

Author(s):

Dearbhaile Catherine Collins ◽

Raghav Sundar ◽

Anastasia Constantidinou ◽

David Dolling ◽

Timothy Anthony Yap ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Metastatic Disease ◽

Distant Metastases ◽

Peritoneal Metastases ◽

Pleural Mesothelioma ◽

Clinical Workflow ◽

Distant Metastatic Disease ◽

High Incidence ◽

Trial Protocols ◽

Metastatic Sites

Abstract BackgroundMalignant pleural mesothelioma (MPM) is traditionally characterized by local destructive spread of the pleura and surrounding tissues. Patient outcomes in MPM with distant metastatic dissemination are lacking. MethodsIn this retrospective study, we reviewed a cohort of 164 MPM patients referred to a Phase I trials unit, aiming to describe identified metastatic sites, and correlate with clinical outcomes. Results67% of patients were diagnosed with distant metastatic disease with a high incidence of bone (19%), visceral (14%), contralateral lung (35%) and peritoneal metastases (22%). Peritoneal metastases were more likely in epithelioid versus biphasic/ sarcomatoid MPM (p=0.015). Overall survival was 23.8 months with no statistical difference in survival between those with distant metastases and those without.ConclusionsThis report highlights the frequency of distant metastases and encourages further radiological investigations in the presence of symptoms. In particular, given the relatively high incidence of bone metastases, bone imaging should be considered in advanced MPM clinical workflow and trial protocols. The presence of distant metastases does not appear to have prognostic implications under existing treatment paradigms. This cohort of MPM patients gives an indication of patterns of metastatic spread that are likely to become prevalent as prognosis improves with emerging treatment paradigms.

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Radiological evaluation of malignant pleural mesothelioma - defining distant metastatic disease

10.21203/rs.3.rs-33715/v1 ◽

2020 ◽

Author(s):

Dearbhaile Catherine Collins ◽

Raghav Sundar ◽

Anastasia Constantidinou ◽

David Dolling ◽

Timothy Anthony Yap ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Metastatic Disease ◽

Distant Metastases ◽

Peritoneal Metastases ◽

Pleural Mesothelioma ◽

Clinical Workflow ◽

Distant Metastatic Disease ◽

High Incidence ◽

Trial Protocols ◽

Metastatic Sites

Abstract Background Malignant pleural mesothelioma (MPM) is traditionally characterized by local destructive spread of the pleura and surrounding tissues. Patient outcomes in MPM with distant metastatic dissemination are lacking. Methods In this retrospective study, we reviewed a cohort of 164 MPM patients referred to a Phase I trials unit, describe identified metastatic sites, and correlate with clinical outcomes. Results 67% of patients were diagnosed with distant metastatic disease with a high incidence of bone (19%), visceral (14%), contralateral lung (35%) and peritoneal metastases (22%). Peritoneal metastases were more likely in epithelioid versus biphasic/ sarcomatoid MPM (p = 0.015). Overall survival was 23.8 months with no statistical difference in survival between those with distant metastases and those without. Conclusions This report highlights the frequency of distant metastases and encourages further radiological investigations in the presence of symptoms. In particular, given the relatively high incidence of bone metastases, bone imaging should be considered in advanced MPM clinical workflow and trial protocols. The presence of distant metastases does not appear to have prognostic implications under existing treatment paradigms. This cohort of MPM patients gives an indication of patterns of metastatic spread that are likely to become prevalent as prognosis improves with emerging treatment paradigms.

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Correction to: Radiological evaluation of malignant pleural mesothelioma - defining distant metastatic disease

BMC Cancer ◽

10.1186/s12885-021-07999-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dearbhaile Catherine Collins ◽

Raghav Sundar ◽

Anastasia Constantinidou ◽

David Dolling ◽

Timothy Anthony Yap ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Metastatic Disease ◽

Pleural Mesothelioma ◽

Radiological Evaluation ◽

Distant Metastatic Disease

An amendment to this paper has been published and can be accessed via the original article.

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Patterns of metastases in malignant pleural mesothelioma in the modern era: Redefining the spread of an old disease.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8556 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8556-8556 ◽

Cited By ~ 7

Author(s):

Dearbhaile Catherine Collins ◽

Anastasia Constantinidou ◽

Raghav Sundar ◽

Maxime Chenard-Poirier ◽

Timothy Anthony Yap ◽

...

Keyword(s):

Bone Metastases ◽

Malignant Pleural Mesothelioma ◽

Survival Data ◽

Lung Metastases ◽

Case Reports ◽

Pleural Mesothelioma ◽

Clinical Workflow ◽

Trial Protocols ◽

Type Pattern ◽

Metastatic Patterns

8556 Background: Malignant pleural mesothelioma (MPM) has been historically documented as a locally infiltrative disease in large series from the early 1980s. With the changing landscape of cancer diagnosis and treatment, increased areas of unusual metastases have been published as case reports. With no standard second-line therapies for MPM, referral to early phase trial units is common. We report the metastatic patterns of a large cohort of MPM patients treated at the Royal Marsden Drug Development Unit (DDU). Methods: Clinical data was gathered for MPM patients referred to the DDU from 1992 to 2016. Radiographic details were collected from CT, bone scan and FDG PET imaging. Prior treatment, response, somatic mutations, clinical trial and survival data was obtained from medical records. Results: From the database, 165 evaluable patients with MPM were identified. Median age at diagnosis was 64 years (range 37–90) and 76% were male. Epithelioid MPM comprised 81% and 65% were right sided. Bone metastases were reported in 20%, with the majority lytic in nature ( Table). Peritoneal and omental disease was evident in 24% with ascites in 16%. In 11% of cases lung metastases presented as diffuse miliary-type pattern. Visceral metastases (15%) were predominantly liver (78%), but also occurred in adrenals, spleen and kidneys. Symptomatic brain metastases were recorded in 3%. Median overall survival was 24.2 months (95% CI: 20.8 - 29.2). Conclusions: This large study documents the metastatic patterns of advanced MPM in the 21st century and highlights an increased frequency of traditionally unexpected sites of metastases. Higher than expected incidence of lytic bone metastases (20%) suggests consideration of bone imaging in advanced MPM clinical workflow and trial protocols. [Table: see text]

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DNA Methylation of FKBP5 as Predictor of Overall Survival in Malignant Pleural Mesothelioma

Cancers ◽

10.3390/cancers12113470 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3470

Author(s):

Giovanni Cugliari ◽

Chiara Catalano ◽

Simonetta Guarrera ◽

Alessandra Allione ◽

Elisabetta Casalone ◽

...

Keyword(s):

Dna Methylation ◽

Overall Survival ◽

Malignant Pleural Mesothelioma ◽

P Value ◽

Pleural Mesothelioma ◽

Lymphocyte To Monocyte Ratio ◽

High Incidence ◽

Aggressive Tumor ◽

Independent Marker ◽

The Relationship

Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 × 10−9) OS-related differential methylation of a single-CpG (cg03546163), located in the 5′UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm < 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm ≥ 0.45 (mean: 243 versus 534 days; p value< 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM.

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Distant metastases in ovarian carcinoma

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200303000-00004 ◽

2003 ◽

Vol 13 (2) ◽

pp. 125-129 ◽

Cited By ~ 24

Author(s):

G. Cormio ◽

C. Rossi ◽

A. Cazzolla ◽

L. Resta ◽

G. Loverro ◽

...

Keyword(s):

Ovarian Cancer ◽

Prognostic Factors ◽

Ovarian Carcinoma ◽

Metastatic Disease ◽

Stage Iv ◽

Distant Metastases ◽

Distant Disease ◽

Distant Metastatic Disease ◽

Interval Time ◽

Stage Iv Disease

Distant metastases are unusual at presentation and during the course of ovarian carcinoma. The aim of the present study was to determine the incidence and prognostic factors of distant metastases consistent with stage IV disease in ovarian cancer patients. A retrospective chart review was conducted on 162 patients with epithelial ovarian carcinoma treated at our Unit between 1991 and 2000. Pertinent clinical information, pathologic data, treatment, and prognostic factors for survival following documentation of distant metastatic disease were collected. The significance of the association between metastatic status and various clinical variables was assessed using the standard chi-square test. Survival time was calculated from the time of diagnosis of ovarian cancer and from the time of diagnosis of the distant metastases. A logistic regression procedure was used to estimate the odds of metastatic status given the presence of certain clinical variables. A total of 67 metastatic sites were diagnosed in 50 patients. Thirteen patients (8%) had distant metastatic disease at the time of diagnosis, 37 patients (22%) had distant metastases at the time of recurrent of progressive disease. Site of metastases were: liver, 21; pleura, 11; lung, 8; central nervous system and skin, 7 each; extra-abdominal lymph nodes and spleen, 5 each; bone, 2; and breast, 1. Significant risk factors for the development of distant metastases were stage, grade, and lymph node involvement. Median interval time between diagnosis of ovarian cancer and documentation of metastatic disease was 44 months (range 3–105), and at the time of diagnosis of distant disease, 36 of 50 patients (72%) had other sites of disease (intra-abdominal or extra-abdominal). Median survival from diagnosis of distant disease was 12 months (range 1–58). In univariate analysis performance status (P = 0.03), the presence of other sites of disease (P = 0.04) and interval time between diagnosis of ovarian cancer and documentation of distant metases (P = 0.03) were the only factors significantly associated with survival. Long interval time remained significant for prognosis in multivariate analysis also (P = 0.04). Distant metastasis consistent with stage IV disease is a late complication that occurs in about one third of ovarian cancer patients. Prognosis after documentation of distant metastases is poor. We conclude the most important prognostic factor associated with survival is the interval time between diagnosis of ovarian cancer and documentation of distant metastases.

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Expanded criteria for pretreatment staging CT in breast cancer

BJS Open ◽

10.1093/bjsopen/zraa006 ◽

2021 ◽

Vol 5 (2) ◽

Author(s):

N Roszkowski ◽

S S Lam ◽

E Copson ◽

R I Cutress ◽

R Oeppen

Keyword(s):

Breast Cancer ◽

Metastatic Disease ◽

Tumour Size ◽

Multivariable Analysis ◽

Distant Metastases ◽

Outcome Data ◽

Axillary Lymph Nodes ◽

Axillary Lymph ◽

Newly Diagnosed ◽

Distant Metastatic Disease

Abstract Background There is wide variation in the approach to staging for distant metastatic disease in breast cancer. This study sought to identify factors predictive of distant metastatic disease at presentation to enable appropriate selection of patients for pretreatment CT. Methods Data were collected retrospectively for all patients with newly diagnosed breast cancer (screening and symptomatic) over 3 years (2014–2017). Detailed demographic, pathological, biological, and management data were recorded at presentation, and outcome data were recorded after follow-up. Binomial logistic regression was used to identify variables independently associated with distant metastatic disease at presentation. Results A total of 1377 patients with newly diagnosed breast cancer were identified, of whom 1025 had complete data; 323 staging CT examinations were performed. Distant metastases were identified at presentation in 47 (4.6 per cent). Some 30 of 47 patients with metastatic disease met established criteria for staging (T4, recurrence, symptoms of possible distant metastases), leaving 17 patients with metastatic disease potentially missed by use of these criteria alone. Multivariable analysis showed that tumour size at least 3 cm combined with sonographically abnormal axillary lymph nodes predicted a high probability of distant metastatic disease at presentation (positive predictive value 18.8 per cent, odds ratio 4.83, P < 0.001). Addition of this criterion increased the positive CT rate to 17.1 per cent. Conclusion Selective pretreatment CT staging can be further optimized with the addition of tumour size at least 3 cm with abnormal axillary nodes to established staging criteria.

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