H3K27 trimethylation loss in malignant peripheral nerve sheath tumor: a systematic review and meta-analysis with diagnostic implications

Journal of Neuro-Oncology - Multiple studies have reported the loss of trimethylation at lysine (K) 27 on histone 3 (H3K27me3) in high-grade malignant peripheral nerve sheath tumors (MPNSTs)....     

Prospective Comparison of Toxicity and Cosmetic Outcome After Accelerated Partial Breast Irradiation With Conformal External Beam Radiotherapy or Single-Entry Multilumen Intracavitary Brachytherapy

Purpose

This study aimed to prospectively characterize toxicity and cosmesis after accelerated partial breast irradiation (APBI) with 3-dimensional conformal radiation therapy (CRT) or single-entry, multilumen, intracavitary brachytherapy.

m7FLIPI and targeted sequencing in high‐risk follicular lymphoma

Patients with follicular lymphoma (FL) refractory to front‐line immunochemotherapy (ICT) have a poor overall survival (OS). Gene mutation analysis may be more accurate than classical risk factors to pick out these patients before treatment. This study aimed to describe the prevalence of selected genetic mutations in a cohort of patients with high‐risk FL. Twenty‐five patients with FL refractory to front‐line ICT and 10 non‐refractory patients matched for age, sex, and FLIPI score were included. We sequenced 18 genes (custom targeted sequencing panel) previously reported to potentially have prognostic impact, including the seven genes necessary to determine m7FLIPI risk. The 35 patients had a median age of 62. The FLIPI and FLIPI2 were high in 27 (84%) and 14 (48%), respectively. Three‐year progression‐free survival (PFS) and OS probabilities were 25% (95% CI, 13%‐41%) and 53% (34%‐69%), respectively. There were 73 variants in the 18 genes among the 35 patients. The median number of mutations per patient was 1 (interquartile range, 0‐3). The most commonly mutated genes were CREBBP (11 of 35, 31%) and EP300 (10 of 35, 29%). EP300 mutations were associated with refractoriness to treatment (10 of 25 among refractory and 0 of 10 among non‐refractory). In conclusion, in this study, patients with high‐risk follicular lymphoma were genetically heterogeneous.     

Correction to: Serum microRNA is a biomarker for post-operative monitoring in glioma

Journal of Neuro-Oncology - We performed a systematic review and meta-analysis of clinical outcomes for patients with acromegaly treated with stereotactic radiosurgery (SRS). Primary outcomes were...     

The KL-VS sequence variant of Klotho and cancer risk in BRCA1 and BRCA2 mutation carriers

Klotho (KL) is a putative tumor suppressor gene in breast and pancreatic cancers located at chromosome 13q12. A functional sequence variant of Klotho (KL-VS) was previously reported to modify breast cancer risk in Jewish BRCA1 mutation carriers. The effect of this variant on breast and ovarian cancer risks in non-Jewish BRCA1/BRCA2 mutation carriers has not been reported. The KL-VS variant was genotyped in women of European ancestry carrying a BRCA mutation: 5,741 BRCA1 mutation carriers (2,997 with breast cancer, 705 with ovarian cancer, and 2,039 cancer free women) and 3,339 BRCA2 mutation carriers (1,846 with breast cancer, 207 with ovarian cancer, and 1,286 cancer free women) from 16 centers. Genotyping was accomplished using TaqMan^® allelic discrimination or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Data were analyzed within a retrospective cohort approach, stratified by country of origin and Ashkenazi Jewish origin. The per-allele hazard ratio (HR) for breast cancer was 1.02 (95% CI 0.93–1.12, P = 0.66) for BRCA1 mutation carriers and 0.92 (95% CI 0.82–1.04, P = 0.17) for BRCA2 mutation carriers. Results remained unaltered when analysis excluded prevalent breast cancer cases. Similarly, the per-allele HR for ovarian cancer was 1.01 (95% CI 0.84–1.20, P = 0.95) for BRCA1 mutation carriers and 0.9 (95% CI 0.66–1.22, P = 0.45) for BRCA2 mutation carriers. The risk did not change when carriers of the 6174delT mutation were excluded. There was a lack of association of the KL-VS Klotho variant with either breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.     

Diabetes,diabetes treatment and breast cancer prognosis

Biomarkers of bone turnover, including urine N-telopeptide (uNTx), have been used as surrogate measures of response to bone-targeted therapies. Vascular endothelial growth factor (VEGF) levels correlate with extent of bone metastases. We assessed whether vandetanib, an inhibitor of VEGF, epidermal growth factor receptor and RET signalling, improved uNTx response when added to fulvestrant (F) in breast cancer patients with bone metastases. Postmenopausal patients with bone predominant, hormone-receptor-positive metastatic breast cancer were randomised to F (500 mg IM days 1, 15, 29, then monthly) with either vandetanib (100 mg PO OD) (FV) or placebo (FP). The primary objective was uNTx response. Secondary objectives included PFS, OS, RECIST response, pain scores and toxicity. Sixty-one patients were allocated to FV and 68 to FP. Out of 127 analyzable patients, an uNTx response occurred in 66 % for FV and 54 % for FP (p = 0.21). No difference was detected between groups for PFS; HR = 0.95 (95 % CI 0.65–1.38) or OS HR = 0.69 (95 % CI 0.37–1.31). For the 62 patients with measurable disease, clinical benefit rates were 41 and 43 %, respectively (p = 0.47). Serious adverse events were similar, 3.3 % for FV versus 5.9 % for FP. Elevated baseline uNTx (>65 nM BCE/mmol Cr) was prognostic for PFS, HR = 1.55 (95 % CI 1.04–2.30) and for OS, HR = 2.32 (95 % CI 1.25–4.33). The addition of vandetanib to fulvestrant did not improve biomarker response, PFS or OS in patients with bone metastases. Baseline bone turnover was prognostic for PFS and OS.     

Association between personal use of hair dyes and lymphoid neoplasms in Europe

Hair dyes have been evaluated as possibly being mutagenic and carcinogenic in animals. Studies of the association between human cancer risk and use of hair dyes have yielded inconsistent results. The authors evaluated the risk of lymphoid malignancies associated with personal use of hair dyes. The analysis included 2,302 incident cases of lymphoid neoplasms and 2,417 hospital- or population-based controls from the Czech Republic, France, Germany, Ireland, Italy, and Spain (1998-2003). Use of hair dyes was reported by 74% of women and 7% of men. Lymphoma risk among dye users was significantly increased by 19% in comparison with never use (odds ratio (OR) = 1.19, 95% confidence interval (CI): 1.00, 1.41) and by 26% among persons who used hair dyes 12 or more times per year (OR = 1.26, 95% CI: 1.00, 1.60; p for linear trend = 0.414). Lymphoma risk was significantly higher among persons who had started coloring their hair before 1980 (OR = 1.37, 95% CI: 1.09, 1.72) and persons who had used hair dyes only before 1980 (OR = 1.62, 95% CI: 1.10, 2.40). Personal use of hair dyes is associated with a moderate increase in lymphoma risk, particularly among women and persons who used dyes before 1980. Specific compounds associated with this risk remain to be elucidated.