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Ljubljana, Slovenia

Strojan P.,Institute of Oncology Ljubljana
Radiology and Oncology | Year: 2010

Background. In melanoma, radiotherapy has generally been considered as a palliative treatment option indicated only for advanced cases or disseminated disease. In the 70s of the previous century, the technological advances in radiotherapy, linked to rapid development of computer sciences, resulted in restored interest for radiotherapy in melanoma management. Although a fundamental lack of well designed prospective and/or randomized clinical trials critically influenced the integration of radiotherapy into treatment strategies in melanoma, radiotherapy was recently recognized as an indispensable part in the multidisciplinary management of patients with melanoma. Altogether, approximately 23% of melanoma patients should receive at least one course of radiotherapy during the course of the disease. In this review, radiobiological properties of melanoma that govern the decisions for the fractionation patterns used in the treatment of this disease are described. Moreover, the indications for irradiation and the results of pertinent clinical studies from the literature, creating a rationale for the use of radiotherapy in the management of this disease, are reviewed and a brief description of radiotherapy techniques is given. Conclusions. Basic treatment modality in melanoma is surgery. However, whenever surgery is not radical or there are adverse prognostic factors identified on histopathological examination of resected tissue specimen, it needs to be supplemented. Also, in patients with unresectable disease or in those not being suitable for major surgery or who refuse proposed surgical intervention, other effective mode(s) of therapy need to be implemented. From this perspective, supported by clinical experiences and literature results, radiotherapy is a valuable option: it is effective and safe, in curative and palliative setting.

Cunningham D.,Royal Marsden Hospital | Lang I.,National Institute of Oncology | Marcuello E.,Hospital de Sant Pau de Barcelona | Lorusso V.,Italian National Cancer Institute | And 7 more authors.
The Lancet Oncology | Year: 2013

Background: Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed to assess the efficacy and safety of bevacizumab plus capecitabine compared with capecitabine alone in elderly patients with metastatic colorectal cancer. Methods: For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated, unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratified by performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m2 orally twice a day on days 1-14) alone or with bevacizumab (7·5 mg/kg intravenously on day 1), given every 3 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population. The primary endpoint was progression-free survival. The trial is registered with ClinicalTrials.gov, number NCT00484939. Findings: From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 70-87) were recruited from 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was significantly longer with bevacizumab and capecitabine than with capecitabine alone (median 9·1 months [95% CI 7·3-11·4] vs 5·1 months [4·2-6·3]; hazard ratio 0·53 [0·41-0·69]; p<0·0001). Treatment-related adverse events of grade 3 or worse occurred in 53 (40%) patients in the combination group and 30 (22%) in the capecitabine group, and treatment-related serious adverse events in 19 (14%) and 11 (8%) patients. The most common grade 3 or worse adverse events of special interest for bevacizumab or chemotherapy were hand-foot syndrome (21 [16%] vs nine [7%]), diarrhoea (nine [7%] vs nine [7%]), and venous thromboembolic events (11 [8%] vs six [4%]). Treatment-related deaths occurred in five patients in the combination group and four in the capecitabine group. The most common any-grade adverse event of special interest for bevacizumab was haemorrhage (34 [25%] vs nine [7%]). Interpretation: The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer. Funding: F Hoffmann-La Roche. © 2013 Elsevier Ltd.

Prijic S.,Nanotesla Institute | Sersa G.,Institute of Oncology Ljubljana
Radiology and Oncology | Year: 2011

Background. Many different types of nanoparticles, magnetic nanoparticles being just a category among them, offer exciting opportunities for technologies at the interfaces between chemistry, physics and biology. Some magnetic nanoparticles have already been utilized in clinical practice as contrast enhancing agents for magnetic resonance imaging (MRI). However, their physicochemical properties are constantly being improved upon also for other biological applications, such as magnetically-guided delivery systems for different therapeutics. By exposure of magnetic nanoparticles with attached therapeutics to an external magnetic field with appropriate characteristics, they are concentrated and retained at the preferred site which enables the targeted delivery of therapeutics to the desired spot. Conclusions. The idea of binding chemotherapeutics to magnetic nanoparticles has been around for 30 years, however, no magnetic nanoparticles as delivery systems have yet been approved for clinical practice. Recently, binding of nucleic acids to magnetic nanoparticles has been demonstrated as a successful non-viral transfection method of different cell lines in vitro. With the optimization of this method called magnetofection, it will hopefully become another form of gene delivery for the treatment of cancer.

Ocana A.,Albacete University Hospital | Vera-Badillo F.,Princess Margaret Hospital | Seruga B.,Institute of Oncology Ljubljana | Templeton A.,Princess Margaret Hospital | And 2 more authors.
Journal of the National Cancer Institute | Year: 2013

Background The human epidermal growth factor receptor 3 (HER3) is an ErbB/HER family member that dimerizes with other ErbB receptors such as HER2. Numerous agents against HER3 are in clinical development despite variable data for the prognostic impact of HER3 expression. Here we report a meta-analysis of the association of HER3 expression and survival in solid tumors. Methods PubMed was searched for studies evaluating expression of HER3 (as measured by immunohistochemistry) and overall survival (OS) in solid tumors. Published data were extracted and computed into odds ratios (ORs) for death at 3 and 5 years. Data were pooled using the Mantel-Haenszel random-effect model. All statistical tests were two-sided. Results Analysis included 12 studies: three that evaluated colorectal cancer, two that evaluated gastric cancer, two that evaluated breast cancer, and one each that evaluated melanoma, ovarian cancer, head and neck cancer, pancreatic cancer, and cervical cancer. The median percentage of cancers with HER3 overexpression was 42.2%. HER3 was associated with worse OS at both 3 years (OR = 2.24, 95% confidence interval [CI] = 1.77 to 2.83, P < .001) and 5 years (OR = 2.20, 95% CI = 1.75 to 2.76, P < .001). Among studies with common HER2 overexpression (breast, gastric, and ovarian cancers), the magnitude of effect of HER3 on OS was statistically significantly greater for both 3-year OS (OR = 3.12, 95% CI = 2.24 to 4.37) and 5-year OS (OR = 2.84, 95% CI = 2.09 to 3.88). Conclusions Expression of HER3 is associated with worse survival in solid tumors. The influence of HER3 may be greater in those tumors where HER2 is commonly overexpressed. © The Author 2012. Published by Oxford University Press. All rights reserved.

Background. Primary central nervous system lymphomas (PCNSL) are rare variants of extranodal non-Hodgkin's lymphomas that are nowadays primarily treated with high-dose methotrexate or methotrexate-based chemotherapy with or without radiation therapy. The optimal treatment of PCNSL is still unknown and there are differences in clinical practice. Patients and methods. With a retrospective research we evaluated our series of patients with PCNSL in regards to the patient's characteristics, treatment results, disease specific survival and overall survival. Fifty nine patients who attended the Institute of Oncology Ljubljana between 1995 and 2010 were treated according to the protocol that was valid at the time of the patient's admission. Between 1995 and 1999, the systemic treatment was classical CHOP (cyclophosphamide, doxorubicin, vincristine, steroids) chemotherapy, and later on high-dose methotrexate either alone or in combination with other agents. From 1999 onwards, radiation therapy was applied according to the patient's age and response to chemotherapy, prior to that all patients treated with CHOP were also irradiated. Patients ineligible for the systemic treatment were treated with sole radiation therapy. Results. There was a strong female predominance in our series and the median age at diagnosis was 59.8 years. Patients had predominantly aggressive B cell lymphomas (69.5%), one patient had marginal cell lymphoma and two patients T cell lymphoma. In total, 20.3% of patients were treated just with chemotherapy, 33.9% with combined therapy and 42.4% with sole radiation therapy. The overall response rate to the primary treatment in patients treated with sole chemotherapy was 33.3%, in patients treated with combined therapy 65% and in patients treated only with radiation therapy 56%, respectively. In terms of response duration, significantly better results were achieved with combined therapy or radiation therapy alone compared to sole chemotherapy (p<0.0006). The median overall survival of the whole cohort was 11 months and the overall survival was significantly affected by the patient's age. The longest overall survival was observed in patients treated with combined therapy (median survival of 39 months). Patients treated just with radiation therapy had a median overall survival of 9 months and those treated with sole chemotherapy of 4.5 months, respectively. Conclusions. The treatment outcomes in ordinary clinical practice are definitely inferior to the ones reported in clinical trials. The now standard treatment with high-dose methotrexate with or without radiation therapy is sometimes too aggressive and, therefore, a careful selection on the basis of patient's age, performance status and concomitant diseases of those eligible for such treatment is mandatory. According to our results from a retrospective study, radiation therapy should not be excluded from the primary treatment.

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