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Why do patients with radiation-induced sarcomas have a poor sarcoma-related survival?

ABSTRACT: BACKGROUND: This study aims to provide reasons for the poor sarcoma-related survival in patients with radiation-induced sarcoma (RIS). METHODS: We performed a case-control study comparing sarcoma-related survival of 98 patients with RIS to that of 239 sporadic high-grade malignant sarcomas. RESULTS: The cumulative sarcoma-related 5-year survival was 32% (95% confidence interval (CI): 22-42) for patients with RIS vs 51% (95% CI: 44-58) for controls (P<0.001). Female gender, central tumour site and incomplete surgical remission were significantly more frequent among RIS patients than in controls. In multivariate analysis incomplete surgical remission (hazard ratio (HR) 4.48, 95% CI: 3.08-6.52), metastases at presentation (HR 2.93, 95% CI: 1.95-4.41), microscopic tumour necrosis (HR 1.88, 95% CI: 1.27-2.78) and central tumour site (HR 1.71, 95% CI: 1.18-2.47) remained significant adverse prognostic factors, but not sarcoma category (RIS vs sporadic). CONCLUSION: The poor prognosis of RIS patients are not due to the previous radiotherapy per se, but related to the unfavourable factors - central tumour site, incomplete surgical remission, microscopic tumour necrosis and the presence of metastases, the two former factors overrepresented in RIS.

SUBMITTER: Bjerkehagen B

PROVIDER: S-EPMC3261679 | biostudies-other | 2012 Jan

REPOSITORIES: biostudies-other

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Project description:Background & aimsAlcohol-related hepatitis (AH) and alcohol-related cirrhosis are grave conditions with poor prognoses. Altered hepatic lipid metabolism can impact disease development and varies between different alcohol-related liver diseases. Therefore, we aimed to investigate lipidomics and metabolomics at various stages of alcohol-related liver diseases and their correlation with survival.MethodsPatients with newly diagnosed alcohol-related cirrhosis, who currently used alcohol (ALC-A), stable outpatients with decompensated alcohol-related cirrhosis with at least 8 weeks of alcohol abstinence (ALC), and patients with AH, were compared with each other and with healthy controls (HC). Circulating lipids and metabolites were analysed using HPLC and mass spectrometry.ResultsForty patients with ALC, 95 with ALC-A, 30 with AH, and 42 HC provided plasma. Lipid levels changed according to disease severity, with generally lower levels in AH and cirrhosis than in the HC group; this was most pronounced for AH, followed by ALC-A. Nine out of 10 free fatty acids differed between cirrhosis groups by relative increases of 0.12-0.66 in ALC compared with the ALC-A group (p <0.0005). For metabolomics, total bile acids increased by 19.7, 31.3, and 80.4 in the ALC, ALC-A, and AH groups, respectively, compared with HC (all p <0.0001). Low sphingolipid ([d42:1] and [d41:1]) levels could not predict 180-day mortality (AUC = 0.73, p = 0.95 and AUC = 0.73, p = 0.95) more accurately than the model for end-stage liver disease score (AUC = 0.71), but did predict 90-day mortality (AUC d42:1 = 0.922, AUC d41:1 = 0.893; pd42:1 = 0.005, pd41:1 = 0.007) more accurately than the MELD score AUCMELD = 0.70, pMELD = 0.19).ConclusionsAlcohol-related severe liver disease is characterised by low lipid levels progressing with severity of liver disease, especially low sphingomyelins, which also associate to poor prognoses.Impact and implicationsLipidomics has the potential to diagnose and risk stratify patients with liver diseases. Lipidomics differed between patients with alcohol-related hepatitis and alcohol-related cirrhosis with and without recent alcohol use. Furthermore, lipidomics could predict short-term mortality and might be suitable as a prognostic tool in the future.Clinical trials registrationScientific Ethics Committee of the Capital Region of Denmark, journal no. H-21013476.

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Why do patients with radiation-induced sarcomas have a poor sarcoma-related survival?

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