Instituto Catalan Of Oncologia

Girona, Spain

Instituto Catalan Of Oncologia

Girona, Spain

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Gomez-Martin C.,GI Cancer Clinical Research Unit | Gomez-Martin C.,Hospital Universitario Sanchinarro | Plaza J.C.,Hospital Universitario Sanchinarro | Pazo-Cid R.,Hospital Universitario Miguel Servet | And 23 more authors.
Journal of Clinical Oncology | Year: 2013

Purpose Previous studies have highlighted the importance of an appropriate human epidermal growth factor receptor 2 (HER2) evaluation for the proper identification of patients eligible for treatment with anti-HER2 targeted therapies. Today, the relationship remains unclear between the level of HER2 amplification and the outcome of HER2-positive gastric cancer treated with first-line chemotherapy with trastuzumab. The aim of this study was to determine whether the level of HER2 gene amplification determined by the HER2/CEP17 ratio and HER2 gene copy number could significantly predict some benefit in overall survival and response to therapy in advanced gastric cancer treated with trastuzumab-based chemotherapy. Patients and Methods Ninety patients with metastatic gastric cancer treated with first-line trastuzumab-based chemotherapy were studied. The optimal cutoff values for HER2/CEP17 ratio and HER2 gene copy number (GCN) for discriminating positive results in terms of response and prolonged survival were determined using receiver operating characteristic curves analyses. Results In this study, a median HER2/CEP17 ratio of 6.11 (95% CI, 2.27 to 21.90) and a median HER2 gene copy number of 11.90 (95% CI, 3.30 to 43.80) were found. A mean HER2/CEP17 ratio of 4.7 was identified as the optimal cutoff value discriminating sensitive and refractory patients (P < .005). Similarly, the optimal cutoff for predicting survival longer than 12 months was 4.45 (P < .005), and for survival longer than 16 months was 5.15 (P <.004). For HER2 GCN, the optimal cutoff values were 9.4, 10.0, and 9.5, respectively (P < .02). Conclusion The level of HER2 gene amplification significantly predicts sensitivity to therapy and overall survival in advanced gastric cancer treated with trastuzumab-based chemotherapy. © 2013 by American Society of Clinical Oncolog.y.


Eriksen J.G.,University of Southern Denmark | Salembier C.,Europe Hospitals | Rivera S.,Gustave Roussy | De Bari B.,University of Lausanne | And 10 more authors.
Radiotherapy and Oncology | Year: 2014

Variability in anatomical contouring is one of the important uncertainties in radiotherapy. FALCON (Fellowship in Anatomic deLineation and CONtouring) is an educational ESTRO (European SocieTy for Radiation and Oncology) project devoted to improve interactive teaching, the homogeneity in contouring and to compare individual contours with endorsed guidelines or expert opinions. This report summarizes the experience from the first 4 years using FALCON for educational activities within ESTRO School and presents the perspectives for the future. © 2014 Elsevier Ireland Ltd. All rights reserved.


Tabernero J.,Autonomous University of Barcelona | Garcia-Carbonero R.,University of Seville | Cassidy J.,Beatson Laboratories | Cassidy J.,Hoffmann-La Roche | And 17 more authors.
Clinical Cancer Research | Year: 2013

Purpose: This randomized, double-blind, placebo-controlled, phase IIb study evaluated adding sorafenib to first-line modified FOLFOX6 (mFOLFOX6) for metastatic colorectal cancer (mCRC). Experimental Design: Patients were randomized to sorafenib (400 mg b.i.d.) or placebo, combined with mFOLFOX6 (oxaliplatin 85 mg/m2; levo-leucovorin 200 mg/m2; fluorouracil 400 mg/m2 bolus and 2400 mg/m2 continuous infusion) every 14 days. Primary endpoint was progression-free survival (PFS). Target sample was 120 events in 180 patients for >85% power (two-sided α = 0.20) to detect an HR = 0.65. Results: Of 198 patients randomized, median PFS for sorafenib plus mFOLFOX6 was 9.1 months versus 8.7 months for placebo plus mFOLFOX6 (HR = 0.88; 95% CI, 0.64-1.23; P = 0.46). There was no difference between treatment arms for overall survival. Subgroup analyses of PFS and overall survival showed no difference between treatment arms by KRAS or BRAF status (mutant and wild type). The most common grade 3/4 adverse events in the sorafenib and placebo arms were neutropenia (48% vs. 22%), peripheral neuropathy (16% vs. 21%), and grade 3 hand-foot skin reaction (20% vs. 0%). Treatment discontinuation because of adverse events was 9% and 6%, respectively. Generally, dose intensity (duration and cumulative doses) was lower in the sorafenib arm than in the placebo arm. Conclusion: This study did not detect a PFS benefit with the addition of sorafenib to first-line mFOLFOX6 for mCRC. KRAS and BRAF status did not seem to impact treatment outcomes but the subgroups were small. These results do not support further development of sorafenib in combination with mFOLFOX6 in molecularly unselected patients with mCRC. ©2013 AACR.


Chaux A.,Institute Patologia e Investigacion | Pfannl R.,Tufts Medical Center | Lloveras B.,Hospital Of Mar | Lloveras B.,Instituto Catalan Of Oncologia | And 11 more authors.
American Journal of Surgical Pathology | Year: 2010

From the pathogenic point of view, penile cancers may be grouped in human papillomavirus-related and unrelated tumors, each one of them with distinctive morphologic features. The former are predominantly composed of small, undifferentiated basaloid cells, with more or less prominent koilocytic changes, and the latter of keratinizing differentiated squamous cells. The same cellular types are observed in precancerous lesions. On the basis of these observations, we constructed a novel nomenclature for penile precancerous lesions and classified them as penile intraepithelial neoplasia (PeIN) of differentiated, warty, basaloid, and warty-basaloid types. The aim of this study was to test the usefulness of immunohistochemical p16 overexpression, considered as a surrogate for high-risk human papillomavirus infection, using this classification system. We pathologically evaluated 141 patients with PeIN, associated (123 cases) and unassociated (18 cases) with invasive cancer. Distribution of PeIN types was: differentiated, 72%; basaloid, 9%; warty-basaloid, 7%; warty, 4%; and mixed, 7%. There was a striking similarity in the morphology of in situ and invasive squamous cell carcinomas. Differentiated PeIN was commonly associated with usual, verrucous, papillary, and other low-grade keratinizing variants of squamous cell carcinoma whereas in basaloid and warty carcinomas the presence of in situ lesions with similar morphology was habitual. We evaluated p16 overexpression using a 4-tiered (0, 1, 2, and 3) pattern-based system. To properly distinguish differentiated PeIN from in situ lesions with warty and/or basaloid features only pattern 3, which requires full-thickness staining in all epithelial cells, was considered positive. Using this approach, there was a significant association of the negative patterns and differentiated PeIN and of the positive pattern and warty, basaloid, and warty-basaloid PeIN (P<0.0001). Basaloid variant had the strongest association. The sensitivity rate of p16 positivity for discriminating types of PeIN was of 82%, with a specificity of 100% and an accuracy of 95%. Lichen sclerosus was identified in 42 cases and their epithelial component was p16 negative in all cases. Although more studies are necessary to confirm these observations, p16 overexpression seems to be a useful tool for discriminating differentiated from warty, basaloid, and warty-basaloid PeIN. © 2010 by Lippincott Williams & Wilkins.


Sastre J.,Charles III University of Madrid | Aranda E.,Hospital Reina Sofia Of Cordoba | Gravalos C.,Hospital 12 Of Octubre Of Madrid | Massuti B.,Hospital General Of Alicante | And 7 more authors.
Critical Reviews in Oncology/Hematology | Year: 2011

Purpose: To evaluate the efficacy and safety of first-line single-agent cetuximab in fit elderly patients with metastatic colorectal cancer, as well as potential molecular predictive factors for efficacy. Patients and methods: Patients aged 70 or older with metastatic CRC without criteria for frailty and no prior treatment for advanced disease were treated with single-agent cetuximab 400mg/m2 followed by weekly 250mg/m2 until disease progression or unacceptable toxicity. Results: Forty-one patients were included. Two patients achieved a complete response and 4 patients had a partial response for an overall response rate of 14.6%. Fifteen patients (36.6%) remained stable. Median time to progression was 2.9 months and median overall survival 11.1 months despite two-third of patients received chemotherapy at progression. Forty-five percent of EGFR gene copy number positive patients by FISH were progression-free at 12 weeks, in contrast with 12% of FISH negative patients (p= 0.04). Grade 3 skin toxicity was reported in 5 patients (12.2%). Hypersensitivity infusion reactions were not reported and there were no toxic deaths. Conclusion: Cetuximab is a safe monoclonal antibody with moderate activity in first-line metastatic colorectal cancer, but the present study does not support the use of cetuximab as single-agent in first-line fit elderly patients with metastatic CRC. © 2009 Elsevier Ireland Ltd.


Paz-Ares L.,Hospital Universitario 12 Of Octubre | Paz-Ares L.,Institute Biomedicina Of Seville And Huvr | Paz-Ares L.,Hospital Universitario Virgen del Rocio | Lopez-Pousa A.,Hospital Santa Creu i Sant Pau | And 13 more authors.
Investigational New Drugs | Year: 2012

Purpose: This study assesses the efficacy, toxicity and pharmacokinetic profile of trabectedin with or without prophylactic dexamethasone co-treatment in patients with recurrent advanced soft tissue sarcoma (STS). Patients and methods: Patients were randomized to receive trabectedin as a 3-h infusion every 3 weeks with dexamethasone or placebo in the first cycle, with the alternate in the second cycle and with the patient's choice subsequently. Due to toxicity, the randomized design was modified to openlabel to make dexamethasone mandatory and the initial dose (1,650 μg/m 2) was reduced to 1,500 μg/m 2 and then to 1,300 μg/m 2. Results: Forty-one patients were enrolled and 35 were evaluable for efficacy. One partial response and 18 disease stabilizations were found. The median PFS and OS were 2.1 and 10.2 months, respectively, with the 3- and 6-month PFS rates indicating activity in pretreated STS. Twenty-three and 27 patients developed transient asymptomatic grade 3/4 AST and ALT elevation, respectively, and 21 patients had grade 3/4 neutropenia. Dose reduction from 1,650 μg/m 2 to 1,300 μg/m 2 decreased the incidence of grade 3/4 thrombocytopenia (26% vs. 0%), neutropenia (51% vs. 25%) and AST increase (76% vs. 25% of patients). Four patients died due to drug-related toxicities (3 with placebo). The total body clearance of trabectedin was 28% higher and half-life was 21% lower with dexamethasone compared to placebo, with no differences in volume of distribution. Conclusions: Trabectedin has confirmed activity in patients with pretreated STS. This study shows that cotreatment with dexamethasone improves the safety of trabectedin by reducing drug-induced hepatotoxicity and myelosuppression. © Springer Science+Business Media, LLC 2010.


Gonzalez-Castillo A.,Hospital Universitari Of Bellvitge | Biondo S.,Hospital Universitari Of Bellvitge | Garcia-Granero A.,Hospital Universitari Of Bellvitge | Cambray M.,Instituto Catalan Of Oncologia | And 2 more authors.
Cirugia Espanola | Year: 2016

Introduction The only curative treatment of pelvic recurrence of rectal cancer is radical resection. The aim of this paper is to analyze our experience in surgery for local recurrence of rectal cancer. Methods We performed a descriptive retrospective analysis of patients treated with curative intent for local recurrence of rectal cancer from May 2000 to January 2014. The presence of resectable liver or lung metastases was not an exclusion criterion. The descriptive results, overall survival and disease free survival are presented. Results A total of 35 patients were included. In 18 patients an abdomino-perineal resection of the remaining rectum was performed. Two of them included excision of lower sacral vertebrae, while in 17 patients, sphincter sparing surgery was performed. The most frequent postoperative complications were pelvic collection and postoperative ileus. Seven patients required reoperation and one patient died. Overall survival at one year was 91.2%, at 2 years 75.6% and at 5 years 37%. Conclusions Local recurrence of rectal cancer is a disease with high curability rate. The only curative option is radical surgery, with acceptable mortality. © 2016 AEC


PubMed | Instituto Catalan Of Oncologia and Hospital Universitari Of Bellvitge
Type: Journal Article | Journal: Cirugia espanola | Year: 2016

The only curative treatment of pelvic recurrence of rectal cancer is radical resection. The aim of this paper is to analyze our experience in surgery for local recurrence of rectal cancer.We performed a descriptive retrospective analysis of patients treated with curative intent for local recurrence of rectal cancer from May 2000 to January 2014. The presence of resectable liver or lung metastases was not an exclusion criterion. The descriptive results, overall survival and disease free survival are presented.A total of 35 patients were included. In 18 patients an abdomino-perineal resection of the remaining rectum was performed. Two of them included excision of lower sacral vertebrae, while in 17 patients, sphincter sparing surgery was performed. The most frequent postoperative complications were pelvic collection and postoperative ileus. Seven patients required reoperation and one patient died. Overall survival at one year was 91.2%, at 2 years 75.6% and at 5 years 37%.Local recurrence of rectal cancer is a disease with high curability rate. The only curative option is radical surgery, with acceptable mortality.


Vinas G.,Instituto Catalan Of Oncologia | Vinas G.,Hospital Universitario Dr Josep Trueta | Puig T.,Hospital Universitario Dr Josep Trueta | Puig T.,University of Girona | And 3 more authors.
Medicina Clinica | Year: 2012

Oxidative stress is a biochemical condition of imbalance between free radicals and antioxidant defence mechanisms. Cancer is an inducing oxidative stress disease. Metabolic changes in neoplastic cells, tumor infiltration by inflammatory cells, malnutrition and specific cancer treatment contribute to high levels of oxidative stress in cancer patients. The toxic effects of oxidative stress on normal cells could be counteracted by use of antioxidants, even though they may abrogate the harmful effects of oxidative stress on tumor cells and prevent apoptosis. Thus, currently, there is not enough scientific evidence to support the use of antioxidants in patients with cancer. © 2011 Elsevier España, S.L. All rights reserved.

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