Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): S. Valpione, G. Gremel, P. Mundra, P. Middlehurst, E. Galvani, M.R. Girotti, R.J. Lee, G. Garner, N. Dhomen, P.C. Lorigan, R. Marais
IntroductionTumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients.Materials and methodsA prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients.ResultsBaseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm³), P = 0.024).ConclusionsWe have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.



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Prognostic impact of interval breast cancer detection in women with pT1a N0M0 breast cancer with HER2-positive status: Results from a multicentre population-based cancer registry study

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): A. Musolino, F. Falcini, A. Sikokis, D. Boggiani, A. Rimanti, B. Pellegrino, E.M. Silini, N. Campanini, E. Barbieri, C. Zamagni, R. Degli Esposti, L. Cortesi, G. Bisagni, L. Cavanna, A. Frassoldati, P. Sgargi, M. Michiara
BackgroundAlthough human epidermal growth factor receptor 2 (HER2) overexpression is associated with poor prognosis, patients (pts) with pT1a N0M0 breast cancers (BCs) have an excellent outcome across all subtypes. Interval cancers (ICs) have poorer survival than screen-detected (SD) tumours, and an association has been reported between ICs and HER2 overexpression. We aimed to determine, in a general population of pT1a N0M0 BCs with known screening status, whether HER2-positive ICs have a poorer outcome than HER2-positive SD cancers.MethodsWe evaluated all incident pT1a N0M0 BCs (n = 874) collected in the Emilia-Romagna region (Italy) from 2003 to 2009 and diagnosed in women aged 50–69. Pts unexposed to screening, with unknown HER2 status and/or treated with adjuvant trastuzumab were excluded from analysis.ResultsSixty-one percent of the BCs were SD, whereas 19% were ICs. BCs with high histologic grade, hormone receptor–negative or HER2-positive status (odds ratio=1.7; 95% confidence interval [CI]: 1.1–2.7) were more likely ICs. Median follow-up was 115 months. The 10-year invasive disease-free survival (iDFS) for HER2-positive ICs was lower than that for HER2-positive SD cancers: 75.0% (95% CI: 55.5%–94.5%) versus 93.8% (95% CI: 86.5%–100%). An interaction between ICs and HER2-positive status was found for poorer iDFS after adjusting for prognostic variables (HR = 5.3; 95% CI: 1.6–16.7).ConclusionsIC detection may identify pts with HER2-positive pT1a N0M0 tumours in whom the rate of recurrence justifies consideration for conventional, anti-HER2, adjuvant treatment.



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Corrigendum to “Loss of tight junction plaque molecules in breast cancer tissues is associated with a poor prognosis in patients with breast cancer” [Eur J Cancer 40 (18) (2004) 2717–2725]

Publication date: Available online 23 November 2017
Source:European Journal of Cancer
Author(s): Tracey A. Martin, Gareth Watkins, Robert E. Mansel, Wen G. Jiang




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Overall survival in MERiDiAN, a double-blind placebo-controlled randomised phase III trial evaluating first-line bevacizumab plus paclitaxel for HER2-negative metastatic breast cancer

Publication date: Available online 23 November 2017
Source:European Journal of Cancer
Author(s): David Miles, David Cameron, Magalie Hilton, Josep Garcia, Joyce O'Shaughnessy




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Confirmed Ceylon krait (Bungarus ceylonicus) envenoming in Sri Lanka resulting in neuromuscular paralysis: a case report

Ceylon krait (Bungarus ceylonicus) is a venomous elapid snake endemic to Sri Lanka. It inhabits shaded home gardens and forests in the wet zone of Sri Lanka and might creep into houses in the night. Despite frequ...

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Correction to: Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old

In the original publication [1] the name of author Jeremy M. Aymard was spelled wrong. The original article was updated to rectify this error.

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Correction to: Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old

In the original publication [1] the name of author Jeremy M. Aymard was spelled wrong. The original article was updated to rectify this error.

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