The transcription factor PPARα is overexpressed and is associated with a favourable prognosis in IDH-wildtype primary glioblastoma.

AIMS: PPARα agonists are in current clinical use as hypolipidaemic agents and show significant antineoplastic effects in human glioblastoma models. To date however, the expression of PPARα in large-scale glioblastoma datasets has not been examined. We aimed to investigate the expression of the transcription factor PPARα in primary glioblastoma, the relationship between PPARα expression and patients' clinicopathological features and other molecular markers associated with gliomagenesis. METHODS AND RESULTS: With protein immunoblotting techniques and reverse transcription quantitative real-time PCR, PPARα was found to be significantly overexpressed in glioblastoma compared with control brain tissue (P = 0.032 and P = 0.005). PPARA gene expression was found to be enriched in the classical glioblastoma subtype within The Cancer Genome Atlas (TCGA) dataset. Although not associated with overall survival when assessed by immunohistochemistry, cross-validation with the TCGA dataset and multivariate analyses identified PPARA gene expression as an independent prognostic marker for overall survival (P = 0.042). Finally, hierarchical clustering revealed novel, significant associations between high PPARA expression and a putative set of glioblastoma molecular mediators including EMX2, AQP4, and NTRK2. CONCLUSIONS: PPARα is overexpressed in primary glioblastoma and high PPARA expression functions as an independent prognostic marker in the glioblastoma TCGA dataset. Further studies are required to explore genetic associations with high PPARA expression and to analyse the predictive role of PPARα expression in glioblastoma models in response to PPARα agonists.

Perforating corneal ulceration in a patient with lung metastatic adenocarcinoma treated with gefitinib: a case report.

We present a case of a sixty-year-old female who presented with sudden onset of painless loss of vision in one eye due to a perforated corneal ulcer, following three months of treatment with gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for metastatic adenocarcinoma of the lung with confirmed EGFR gene mutation. The eye did not show any sign of infection or inflammation and had no associated lid problems to account for the development of corneal ulceration. The patient went on to have a corneal graft surgery but postoperatively developed corneal graft melt. This paper aims to raise awareness among ophthalmologists and oncologists of the probable association between gefitinib and corneal ulceration.

Target localisation for tumour bed radiotherapy in early breast cancer.

INTRODUCTION: To compare clinical and CT techniques in localisation of the tumour bed in patients undergoing adjuvant breast radiotherapy for breast cancer. METHODS: Patients were CT scanned in the treatment position following clinical delineation of the whole breast, surgical scar and boost volume. Computed tomography boost volumes were contoured in three dimensions. A definitive treatment plan was generated to encompass the CT-localised planning target volume (PTV) with ≥90% isodose using electrons. A hypothetical plan was also generated to cover the clinically determined boost field for comparison. The primary end point was the difference in PTV coverage by the 90% isodose between the plans based on clinically and CT localised boost volumes. RESULTS: The plans for 50 patients were evaluated. The median percentage of PTV encompassed by the 90% isodose using the clinical and CT techniques was 29% (range 5-90%) and 83% (range 25-100%), respectively. PTV coverage by the 90% isodose using the clinical technique was at least 10% less than that using CT technique in 88% of patients (95% confidence interval 77-95%; P < 0.0001). CONCLUSION: Tumour bed boost PTV coverage was insufficient using clinical determination as compared with CT localisation. This study supports CT planning for target volume localisation of the tumour bed boost in patients treated with breast-conserving therapy for breast cancer.

Extended survival in women with brain metastases from HER2 overexpressing breast cancer.

OBJECTIVES: Brain metastases (BM) are a significant complication of metastatic breast cancer (MBC). The high incidence of BM in HER2 overexpressing MBC is now well recognized, however, the optimal management of such patients is not yet clearly defined. We aimed to analyze factors affecting survival after diagnosis of BM in patients treated in our center. MATERIALS AND METHODS: Retrospective analysis of survival in all patients treated with antineoplastic therapy for BM from MBC in our institution between May 1st 2002 and April 30th 2005, according to HER2 expression and use of trastuzumab after diagnosis of BM. RESULTS: The median survival of the 26 patients with HER2 overexpressing disease after diagnosis of BM was significantly longer than that of the 60 patients with HER2 nonoverexpressing disease (6.2 vs. 3.8 months, P = 0.027). Further analysis revealed that this seems to be due to the favorable outcome of the 70% (n = 18) of HER2 overexpressing patients who received trastuzumab after BM were diagnosed. Median survival of this group was 11.9 months, compared with 3.8 months (HER2 nonoverexpressing disease, P = 0.002) and 3.0 months (HER2 overexpressing disease not treated with trastuzumab after development of BM, P = 0.05). CONCLUSION: Patients with HER2 overexpressing MBC who received trastuzumab after diagnosis of BM survived longer than expected. This finding justifies an active therapeutic approach: disease progression within central nervous system does not preclude benefit from trastuzumab treatment.