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Molina-Ruiz A.M.,Fundacion Jimenez Diaz | Sanmartin O.,Fundacion Instituto Valenciano Of Oncologia | Santonja C.,Fundacion Jimenez Diaz | Kutzner H.,Dermatohistopathologisches Gemeinschaftslabor | Requena L.,Fundacion Jimenez Diaz
Journal of the American Academy of Dermatology | Year: 2013

Background: Polymorphous light eruption (PLE) is the most common form of idiopathic photodermatosis. Several morphologic variants of PLE have been described, including a localized form of PLE primarily affecting the helices of the ears. To our knowledge, the presence of lesions on the elbows as the unique manifestation of PLE has not yet been reported. We have studied 9 patients presenting with a recurrent eruption on the elbows, with clinical and histopathologic features indistinguishable from PLE, occurring during springtime. Recently, a peculiar eruption of the elbows, with similar clinical features to our patients, has been proposed as a manifestation of cutaneous lupus erythematosus. Objective: We sought to describe the clinical, histopathological, and immunohistochemical features of this peculiar eruption of the elbows. Methods: Nine patients presenting a recurrent spring eruption on the elbows, collected from April 1989 to June 2012, were retrospectively analyzed. We studied their clinical and histopathological features, and the immunophenotype of the infiltrate. Results: Five patients were men and 4 were women. The mean age was 44.7 years. The lesions consisted of pruriginous, erythematous-edematous papules and plaques, located on both elbows. The eruption appeared during the spring or early summer and recurred seasonally. No associated symptoms were present and the eruption regressed spontaneously or with topical corticosteroids after 7 to 15 days. Histopathologically, the lesions showed typical features of PLE, with variable degree of edema in the papillary dermis, and a papillary and reticular dermal perivascular infiltrate mostly composed of small lymphocytes. Immunohistochemical studies demonstrated strong immunoreactivity for CD2, CD4, and CD8, revealing the infiltrate was composed predominantly of T lymphocytes, with a predominance of T-helper over T-cytotoxic lymphocytes. Immunostaining for CD123 was negative, highlighting the absence of plasmacytoid dendritic cells. Other T- and B-cell markers, including CD30, PD-1, CXCL13, FoxP3, CD79a, and CD56 were also negative. Limitations: Retrospective case series design is a limitation. Phototests were not performed. Results of antinuclear antibodies were only available in 1 patient. Conclusions: We believe this recurrent eruption of the elbows represents a distinctive and localized variant of PLE rather than a peculiar manifestation of cutaneous lupus erythematosus and suggest the term "spring and summer eruption of the elbows" for this peculiar condition. The mechanism of this localization on the elbows, with sparing of other photoexposed areas, remains unknown. © 2011 by the American Academy of Dermatology, Inc. Source

Garcia-Donas J.,Hospital Universitario Fundacion Alcorcon | Esteban E.,Hospital Universitario Central Of Asturias | Leandro-Garcia L.J.,Spanish National Cancer Research Center | Castellano D.E.,Hospital Universitario 12 Of Octubre | And 14 more authors.
The Lancet Oncology | Year: 2011

Background: Sunitinib is a tyrosine kinase inhibitor with proven efficacy in renal-cell carcinoma, but some patients do not respond or need dose reductions due to toxicity. Because there are no validated molecular predictors of response or toxicity to sunitinib, we aimed to identify genetic markers predictive of outcome and toxic effects. Methods: In our observational, prospective study we enrolled previously untreated adults (≥18 years) with clear-cell renal-cell carcinoma at 15 institutions in the Spanish Oncology Genitourinary Group in Spain. Patients received sunitinib according to local practice guidelines. We assessed RECIST response, progression-free survival (PFS), overall survival, and toxicity of sunitinib with 16 key polymorphisms in nine genes: VEGFR2 (rs2305948 and rs1870377), VEGFR3 (rs307826, rs448012, and rs307821), PDGFR-α (rs35597368), VEGF-A (rs2010963, rs699947, and rs1570360), IL8 (rs1126647), CYP3A4 (rs2740574), CYP3A5 (rs776746), ABCB1 (rs1045642, rs1128503, and rs2032582), and ABCB2 (rs2231142). We assessed associations with efficacy and toxicity by use of univariable and multivariable analyses (with clinical factors associated with outcomes as covariates). We adjusted for multiplicity using the Bonferroni method; p values of less than 0·0031 before adjustment were deemed to still be significant after adjustment. Findings: We enrolled 101 patients between Oct 10, 2007, and Dec 13, 2010. 95 of these patients were included in toxicity analyses and 89 in the efficacy analyses. Two VEGFR3 missense polymorphisms were associated with reduced PFS with sunitinib on multivariable analysis: rs307826 (hazard ratio [HR] per allele 3·57, 1·75-7·30; p unadjusted=0·00049, p adjusted=0·0079) and rs307821 (3·31, 1·64-6·68; p unadjusted=0·00085, p adjusted=0·014). The CYP3A5 1 (rs776746) high metabolising allele was associated in a multivariable analysis with an increased risk of dose reductions due to toxicity (HR per allele 3·75, 1·67-8·41; p unadjusted=0·0014, p adjusted=0·022). No other SNPs were associated with sunitinib response or toxicity. Interpretation: Polymorphisms in VEGFR3 and CYP3A5 1 might be able to define a subset of patients with renal-cell carcinoma with decreased sunitinib response and tolerability. If confirmed, these results should promote interventional studies testing alternative therapeutic approaches for patients with such variants. Funding: Pfizer. © 2011 Elsevier Ltd. Source

Oza A.M.,Princess Margaret Cancer Center | Cook A.D.,University College London | Pfisterer J.,Gynecologic Oncology Center | Embleton A.,University College London | And 20 more authors.
The Lancet Oncology | Year: 2015

Background: The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial. Methods: ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I-IIa, grade 3 or clear cell histology) or more advanced disease (FIGO stage IIb-IV), with an Eastern Cooperative Oncology Group performance status of 0-2, were enrolled and randomly assigned in a 1:1 ratio to standard chemotherapy (six 3-weekly cycles of intravenous carboplatin [AUC 5 or 6] and paclitaxel 175 mg/m2 of body surface area) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks, given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy. Randomisation was done by a minimisation algorithm stratified by FIGO stage, residual disease, interval between surgery and chemotherapy, and Gynecologic Cancer InterGroup group. The primary endpoint was progression-free survival; the study was also powered to detect a difference in overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375. Findings: Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end of the trial on March 31, 2013, was 48·9 months (IQR 26·6-56·2), at which point 714 patients had died (352 in the chemotherapy group and 362 in the bevacizumab group). Our results showed evidence of non-proportional hazards, so we used the difference in restricted mean survival time as the primary estimate of effect. No overall survival benefit of bevacizumab was recorded (restricted mean survival time 44·6 months [95% CI 43·2-45·9] in the standard chemotherapy group vs 45·5 months [44·2-46·7] in the bevacizumab group; log-rank p=0·85). In an exploratory analysis of a predefined subgroup of 502 patients with poor prognosis disease, 332 (66%) died (174 in the standard chemotherapy group and 158 in the bevacizumab group), and a significant difference in overall survival was noted between women who received bevacizumab plus chemotherapy and those who received chemotherapy alone (restricted mean survival time 34·5 months [95% CI 32·0-37·0] with standard chemotherapy vs 39·3 months [37·0-41·7] with bevacizumab; log-rank p=0·03). However, in non-high-risk patients, the restricted mean survival time did not differ significantly between the two treatment groups (49·7 months [95% CI 48·3-51·1]) in the standard chemotherapy group vs 48·4 months [47·0-49·9] in the bevacizumab group; p=0·20). An updated analysis of progression-free survival showed no difference between treatment groups. During extended follow-up, one further treatment-related grade 3 event (gastrointestinal fistula in a bevacizumab-treated patient), three grade 2 treatment-related events (cardiac failure, sarcoidosis, and foot fracture, all in bevacizumab-treated patients), and one grade 1 treatment-related event (vaginal haemorrhage, in a patient treated with standard chemotherapy) were reported. Interpretation: Bevacizumab, added to platinum-based chemotherapy, did not increase overall survival in the study population as a whole. However, an overall survival benefit was recorded in poor-prognosis patients, which is concordant with the progression-free survival results from ICON7 and GOG-218, and provides further evidence towards the optimum use of bevacizumab in the treatment of ovarian cancer. Funding: The National Institute for Health Research through the UK National Cancer Research Network, the Medical Research Council, and Roche. © 2015 Oza et al. Open Access article distributed under the terms of CC BY. Source

Cervera Deval J.,Fundacion Instituto Valenciano Of Oncologia
Radiologia | Year: 2014

Biomedical imaging makes it possible not only to diagnose and stage cancer, but also to follow up patients and evaluate the response to treatment. RECIST (Response Evaluation Criteria In Solid Tumors) provides a method to monitor the response to treatment based on one dimensional measurements of tumors obtained with reproducible imaging techniques like CT, MRI, and PET. The metabolic changes induced by new treatments modify the biology and behavior of the tumor; occasionally, there is a discrepancy between the patient's clinical condition and the response measured by RECIST, which indicates that functional tests need to be included in the evaluation of the response to treatment. The objective is to review the RECIST criteria to include the contribution of functional imaging to enable the efficacy and effects of the treatment in patients with solid tumors. © 2011 SERAM. Publicado por Elsevier España, S.L. Todos los derechos reservados. Source

Cardoso F.,Champalimaud Cancer Center | Bischoff J.,Otto Von Guericke University of Magdeburg | Brain E.,Hopital Rene Huguenin Institute Curie | Brain E.,HopitalReneHuguenin Institute Curie | And 6 more authors.
Cancer Treatment Reviews | Year: 2013

Endocrine therapy is the corner stone treatment for postmenopausal women with hormone receptor-positive metastatic breast cancer (MBC). Besides tamoxifen and many older agents, recently developed endocrine agents for the treatment of MBC include the third generation aromatase inhibitors (AI) - anastrozole, exemestane, letrozole - and the pure oestrogen receptor antagonist fulvestrant. As treatment of breast cancer evolves, both tamoxifen and the AIs are being increasingly used in the adjuvant setting. As such, a significant proportion of patients with hormone receptor-positive MBC will have previously received tamoxifen, an AI or both, as adjuvant treatment. This has changed the metastatic landscape and has an impact on treatment choices for patients with hormone receptor-positive MBC. In this review, we evaluate the available evidence supporting the use of endocrine therapy for the treatment of hormone receptor-positive MBC. Additionally, we consider the effect of prior adjuvant therapy on treatment choice in the metastatic setting and the optimal treatment sequence. Finally, we discuss endocrine-responsive HER2 positive tumours and the ongoing research initiatives which aim to improve outcomes for patients with MBC. © 2012 Elsevier Ltd. Source

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