Pilocytic astrocytoma with leptomeningeal spread in a patient with incontinentia pigmenti presenting with unilateral nystagmus

Abstract

Incontinentia pigmenti (IP) is a genetic disorder caused by mutations in IKBKG, leading to functional loss of nuclear factor kappa B (NF-ĸB). We report the case of a 6-month-old female child with IP who presented with unilateral nystagmus and was found to have a pilocytic astrocytoma with leptomeningeal spread. Enhanced understanding of the relationship between NF-ĸB, along with its upstream regulators, and tumorigenesis may shed light on whether a subset of patients with IP may be at increased risk for neoplasia.

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Pilocytic astrocytoma with leptomeningeal spread in a patient with incontinentia pigmenti presenting with unilateral nystagmus

Abstract

Incontinentia pigmenti (IP) is a genetic disorder caused by mutations in IKBKG, leading to functional loss of nuclear factor kappa B (NF-ĸB). We report the case of a 6-month-old female child with IP who presented with unilateral nystagmus and was found to have a pilocytic astrocytoma with leptomeningeal spread. Enhanced understanding of the relationship between NF-ĸB, along with its upstream regulators, and tumorigenesis may shed light on whether a subset of patients with IP may be at increased risk for neoplasia.

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Phase II Study of Gemcitabine Plus Sirolimus in Previously Treated Patients with Advanced Soft-Tissue Sarcoma: a Spanish Group for Research on Sarcomas (GEIS) Study

Abstract

Background

Gemcitabine plus sirolimus enhances apoptosis in vitro and increases anti-tumor efficacy in vivo in soft-tissue sarcoma (STS) models.

Objective

The objective of this study was to evaluate the activity and toxicity of the combination of gemcitabine plus sirolimus in patients with STS after failure of standard chemotherapy.

Patients and Methods

Advanced STS patients, previously treated with doxorubicin and/or ifosfamide, were included in this single-arm phase II study. Patients received gemcitabine 800 mg/m² intravenously (iv) at 10 mg/m²/min on days 1 and 8 every 3 weeks plus sirolimus 5 mg daily orally (po). After enrolment of the first 12 patients, the study protocol was amended due to toxicity and the starting dose of sirolimus was reduced to 3 mg daily po. Archival tumor samples were analyzed for extracellular signal-regulated kinase 1 and 2 (ERK1/2) expression and correlated with outcome. The primary endpoint was progression-free rate (PFR) at 3 months.

Results

From May 2012 to May 2013, 28 patients were enrolled at eight centers. PFR at 3 and 6 months was 44% and 20%, respectively, with 12 patients being free of progression at 3 months. Median progression-free survival (PFS) was 1.85 months (95% confidence interval [CI] 0.73–2.97) and median overall survival (OS) was 9.2 months (95% CI 5.8–12.5). No responses were observed. The most common grade 3–4 hematologic toxicities were neutropenia (48%) and leukopenia (41%) and the most frequent grade 3 non-hematologic toxicities were infection (18.5%), transaminitis (15%), fatigue (11%), and pneumonitis (11%). ERK1/2 expression was significantly correlated with PFS (p = 0.026).

Conclusions

The combination of gemcitabine and sirolimus is an active treatment in STS. Further investigation is warranted. ClinicalTrials.gov identifier: NCT01684449.

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12th International HHT Scientific Conference

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12th International HHT Scientific Conference

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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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