A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

<p>Abstract</p> <p>Background</p> <p>Aromatase (<it>CYP19A1</it>) regulates estrogen biosynthesis. Polymorphisms in <it>CYP19A1 </it>have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of <it>CYP19A1 </it>and their effect on response to neoadjuvant letrozole in early BC.</p> <p>Methods</p> <p>We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4^thmonth by World Health Organization (WHO) criteria. Three polymorphisms of <it>CYP19A1</it>, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood.</p> <p>Results</p> <p>Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009).</p> <p>Conclusions</p> <p>Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients.</p

Fractionated stereotactic radiotherapy for uveal melanoma, late clinical results

Purpose: To determine local control, late toxicity and metastatic free survival (MFS) of patients treated with fractionated stereotactic radiation therapy (fSRT) for uveal melanoma (UM). Methods and materials: Between 1999 and 2007, 102 UM patients were included in a prospective study of a single institution (median follow-up (FU) 32 months; median tumor thickness 6 mm); five fractions of 10 Gy were given. Primary endpoints were local tumor control and late toxicity (including visual outcome and eye preservation). Secondary endpoint was MFS. Results: Local tumor control was achieved in 96% of the patients. Fifteen enucleations were performed, 285 months after radiation. Four eyes were enucleated because of local tumor progression. Nine patients developed grade 3 or 4 neovascular glaucoma (NVG), 19 developed severe retinopathy, 13 developed opticoneuropathy grade 3 or 4, 10 developed cataract grade 3, and 10 patients suffered from keratitis sic-ca. Best corrected visual acuity (BCVA) decreased from a mean of 0.26 at diagnosis to 0.16 Conclusions: fSRT is an effective treatment modality for uveal melanoma with a good local control. With that, fSRT is a serious eye sparing treatment modality. However, our FU is relatively short. Also, the number of secondary enucleations is substantial, mainly caused by NVG. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 102 (2012) 219-22

The effect of orbital decompression surgery on refraction and intraocular pressure in patients with thyroid orbitopathy

Purpose: To investigate the effect of orbital decompression surgery in thyroid orbitopathy (TO) on both refractive status and intraocular pressure (IOP). Patients and methods: A prospective, multicentre, consecutive audit of patients undergoing thyroid decompression surgery. Indications for surgery included cosmetically unacceptable proptosis or corneal exposure. Exclusion criteria included the following: previous orbital surgery, glaucoma, corneal disease, steroid use in the preceding 12 months, or an acute optic neuropathy. Automated refraction, keratometry, pachymetry, Hertel exophthalmometry, and IOP were recorded at 1 month pre- and 3 months postoperatively. IOP using the Tono-Pen (mean of three readings) was measured in the primary, upgaze, and downgaze positions. Results: Data were collected from 52 orbits of 33 patients (East Grinstead, New York, and Adelaide). There was no significant difference between pre- and postoperative data for sphere, cylinder, or central corneal thickness (CCT). The mean spherical equivalent was −0.43±1.49 D pre-operatively and −0.28±1.52 D postoperatively. The steepest meridian of corneal curvature was 93.1 degrees pre- and 94.2 degrees postoperatively, with no significant difference. Mean IOP significantly decreased when measuring by Goldmann applanation tonometry (GAT) (2.28 mm Hg, * P=0.001) and Tono-Pen (3.06 mm Hg, * P=<0.0001). IOP measured in upgaze was significantly greater than that in the primary position. Regression analysis between change in IOP and either Hertel exophthalmometry or the number of orbital walls decompressed was non-significant (*Student's t-test). Conclusion: Patients with TO undergoing orbital decompression had, on average, with-the-rule astigmatism not affected by orbital decompression surgery. IOP was significantly reduced by decompression surgery although no relationship between IOP and the degree of decompression was observed.JH Norris, JJ Ross, M Kazim, D Selva, and R Malhotr

Pegylated-liposomal doxorubicin and oral topotecan in eight children with relapsed high-grade malignant brain tumors

The schedule of PEG-liposomal doxorubicin with 30-40 mg/m(2) every 4 weeks in combination with oral topotecan resulted in tumor response, but the toxicity was high. An individualized increasing dose of PEG-liposomal doxorubicin 10-20 mg/m(2) every two weeks is now recommended