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Zamora L.I.,Hospital Universitario Reina Sofia | Forastero C.,Instituto Madrileno Of Oncologia | Guirado D.,Hospital Universitario San Cecilio | Guirado D.,CIBER ISCIII | And 2 more authors.
Medical Physics | Year: 2012

Purpose: To develop a Monte Carlo tool that permits to study the reduction in breast cancer mortality rate due to breast screening programs. Methods: Simulations implement woman histories undergoing a screening program, include a model of survival after local treatment of invasive cancers and use distributions of time gained due to screening detection against symptomatic detection and overall sensitivity of the screening obtained previously. Mortalities for the whole woman population and for those women with ages within the range considered in the program have been calculated. Results: For the whole woman population, a reduction in breast cancer mortality up to 29 has been found for a configuration that includes women aged between 50 and 70 years, with a screening interval of two years and 100 acceptance rate. If an acceptance of 70 is considered, this percentage reduces to 20. If, in the same conditions, the program starts at 40 years, the reduction of the mortality reaches 24 while if the screening interval is one year, this percentage raises to 28. If mortalities are calculated for those women with ages within the range included in the program these reductions are greater and no significant differences are found between the programs with age ranges [50-70] and [40-70]. In the model, radio-induced cancers have no effect in survival. Conclusions: The results agree reasonably well with those of different trials. Mortality reductions of 12-20 (between two and four deaths per year and 105 women) are obtained only for acceptances above 50. This could be considered as a threshold for the acceptance, which appears to be a critical parameter. © 2012 American Association of Physicists in Medicine.


Krengli M.,University of Piemonte Orientale | Calvo F.A.,University Hospital Gregorio Maranon | Sedlmayer F.,Paracelsus Medical University | Sole C.V.,University Hospital Gregorio Maranon | And 23 more authors.
Strahlentherapie und Onkologie | Year: 2013

Background: A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. Materials and methods: In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. Results: The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. Conclusion: This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it. © 2013 Springer Heidelberg Berlin.


Delgado J.M.,Instituto Madrileno Of Oncologia | Morales J.,Instituto Nacional Of Oncologia Y Radiobiologia | McDonnell J.D.,National University of Rosario | Ortiz Lopez P.,International Atomic Energy Agency | And 12 more authors.
Health Physics | Year: 2013

Knowledge and lessons from past accidental exposures in radiotherapy are very helpful in finding safety provisions to prevent recurrence. Disseminating lessons is necessary but not sufficient. There may be additional latent risks for other accidental exposures, which have not been reported or have not occurred, but are possible and may occur in the future if not identified, analyzed, and prevented by safety provisions. Proactive methods are available for anticipating and quantifying risk from potential event sequences. In this work, proactive methods, successfully used in industry, have been adapted and used in radiotherapy. Risk matrix is a tool that can be used in individual hospitals to classify event sequences in levels of risk. As with any anticipative method, the risk matrix involves a systematic search for potential risks; that is, any situation that can cause an accidental exposure. The method contributes new insights: The application of the risk matrix approach has identified that another group of less catastrophic but still severe single-patient events may have a higher probability, resulting in higher risk. The use of the risk matrix approach for safety assessment in individual hospitals would provide an opportunity for self-evaluation and managing the safety measures that are most suitable to the hospital's own conditions. Copyright © 2013 Health Physics Society.


Calvo F.A.,Complutense University of Madrid | Sole C.,Instituto Madrileno Of Oncologia | Ferrer C.,Complejo Hospitalario Of Castellon | Garcia-Sabrido J.L.,Complutense University of Madrid
Revisiones en Cancer | Year: 2012

Adenocarcinoma of the exocrine pancreas is a disease model of particular interest and opportunities for radiotherapy. In comparison has a high morbidity and mortality in the context of intensive multimodal therapy. Radical resection is feasible in only 15-20% of patients, and only 3-4% of all patients presenting with this condition achieve long-term control and cure. Various strategies in the form of neoadjuvant and adjuvant treatment have been employed over the years to improve outcome, with limited success. The contribution of radiotherapy, remains controversial and is an area of active innovation that merits further research in well-conducted multicenter trials at various stages of the disease in combination with systemic agents and exploiting recent advances in the delivery of super-precise radiotherapy. An update of the published literature on the use components of radiotherapy or chemoradiation as an integrated modality in the interdisciplinary approach of various stages of pancreatic adenocarcinoma is reported. A highlight of areas that future trials in this field should target to move forward the efficient treatment in this malignancy are suggested. Copyright © 2012 Aran Ediciones, s. l.


Ashworth A.B.,London Health Sciences Center | Senan S.,VU University Amsterdam | Palma D.A.,London Health Sciences Center | Riquet M.,Georges Pompidou European Hospital | And 12 more authors.
Clinical Lung Cancer | Year: 2014

Introduction/Background An individual patient data metaanalysis was performed to determine clinical outcomes, and to propose a risk stratification system, related to the comprehensive treatment of patients with oligometastatic NSCLC.Materials and Methods After a systematic review of the literature, data were obtained on 757 NSCLC patients with 1 to 5 synchronous or metachronous metastases treated with surgical metastectomy, stereotactic radiotherapy/radiosurgery, or radical external-beam radiotherapy, and curative treatment of the primary lung cancer, from hospitals worldwide. Factors predictive of overall survival (OS) and progression-free survival were evaluated using Cox regression. Risk groups were defined using recursive partitioning analysis (RPA). Analyses were conducted on training and validating sets (two-thirds and one-third of patients, respectively).Results Median OS was 26 months, 1-year OS 70.2%, and 5-year OS 29.4%. Surgery was the most commonly used treatment for the primary tumor (635 patients [83.9%]) and metastases (339 patients [62.3%]). Factors predictive of OS were: synchronous versus metachronous metastases (P <.001), N-stage (P =.002), and adenocarcinoma histology (P =.036); the model remained predictive in the validation set (c-statistic = 0.682). In RPA, 3 risk groups were identified: low-risk, metachronous metastases (5-year OS, 47.8%); intermediate risk, synchronous metastases and N0 disease (5-year OS, 36.2%); and high risk, synchronous metastases and N1/N2 disease (5-year OS, 13.8%).Conclusion Significant OS differences were observed in oligometastatic patients stratified according to type of metastatic presentation, and N status. Long-term survival is common in selected patients with metachronous oligometastases. We propose this risk classification scheme be used in guiding selection of patients for clinical trials of ablative treatment. © 2014 Elsevier Inc.


Feito-Rodriguez M.,Hospital Universitario La Paz | De Lucas-Laguna R.,Hospital Universitario La Paz | Bastian B.C.,University of California at San Francisco | LeBoit P.,University of California at San Francisco | And 5 more authors.
British Journal of Dermatology | Year: 2011

Congenital malignant melanoma within a pre-existing large congenital melanocytic naevus (CMN) is exceedingly rare. Its incidence is difficult to determine due to the small number of reported cases and because of problems associated with diagnosis. Some benign nodular proliferations (called proliferative nodules) arising in CMN, while rare, are significantly more common and can mimic malignant melanoma clinically or histologically. There are no reported cases of congenital melanoma or benign proliferative nodules in CMN in patients who also had eruptive disseminated Spitz naevi. We describe a girl who was noted to have a dark-brown plaque with several large erythematous nodules affecting the scalp at delivery, in addition to multiple erythematous dome-shaped papules that developed in a disseminated manner over several months, beginning at 10 days of age. It was difficult, not only clinically but also histologically, to determine the benign or malignant nature of all of these lesions. As primary cutaneous melanoma, atypical proliferative nodules in CMN, bland CMN or CMN with foci of increased cellularity and Spitz naevi show clear differences in the genetic aberration patterns, comparative genomic hybridization (CGH) could be a diagnostic help in ambiguous cases such as this. CGH performed on this patient showed multiple DNA copy number changes in the most atypical nodule, but such alterations could not be found in the remainder of the lesions. CGH showed differences between the nodular lesions that occurred in the CMN and helped us in supporting the diagnosis of this unique case of benign pro-liferative nodules and a possible congenital melanoma arising in a large CMN, associated with multiple widespread eruptive Spitz naevi. © 2011 British Association of Dermatologists.


Usychkin S.,Instituto Madrileno Of Oncologia | Calvo F.,Instituto Madrileno Of Oncologia | Calvo F.,Hospital Universitario Gregorio Maranon | Dos Santos M.A.,Instituto Madrileno Of Oncologia | And 12 more authors.
Clinical and Translational Oncology | Year: 2013

Introduction: Intra-operative electron beam radiotherapy (IOERT) is an alternative to dose escalation for the treatment of central nervous system tumors. The objective of this study was to describe the feasibility and long-term outcomes of IOERT in the treatment of primary and recurrent gliomas. Materials and methods: From January 1992 through December 2002, all patients treated with IOERT at the Hospital San Francisco de Asis, Madrid/Spain were retrospectively reviewed. The selection criteria included patients with superficial tumors, KPS >70 % and lesions <6 cm. Irradiation was administered in one section. The prescribed dose considered the amount of post-resection residual tumor, previous radiotherapy and the tolerance level of brain structures exposed to IOERT. Results: There were 17 patients (53 %) with newly diagnosed malignant brain gliomas and 15 patients with recurrent tumors. The delivered dose varied from 8 to 20 Gy (median 12.5 Gy) for primary and from 8 to 16 Gy (median 10 Gy) for recurrent tumors. The median overall survival for the entire cohort was 13 months (14 and 10.4 months for the primary and recurrent, respectively). Three patients presented with radionecrosis, one patient with osteomyelitis at the craniotomy bone flap, one with intracerebral hemorrhage, and another patient experienced a pulmonary embolism. Conclusions: IOERT is a feasible technique and can be viewed as a tool in the treatment of newly diagnosed or recurrent brain gliomas. © 2012 Federación de Sociedades Españolas de Oncología (FESEO).


Gonzalez J.A.,Instituto Madrileno Of Oncologia | Gonzalez J.A.,Hospital Universitario Infanta Cristina | Chust M.,Fundacion Instituto Valenciano Of Oncologia Ivo | Delgado R.,Hospital Regional Universitario Carlos Haya | And 3 more authors.
Clinical and Translational Oncology | Year: 2010

Introduction: A survey regarding radiobiological questions in the treatment of lung cancer (LC) was done to study the clinical aspects of radiotherapy in Spain, in order to standardise treatment decisions. Methods and materials: From November 2007 to March 2008, a survey was performed among radiation oncologists in Spain specialising in LC treatment via e-mail, which included questions regarding different radiobiological aspects of radiotherapy LC treatment. The extent of the resulting material made it necessary to divide it into two parts; the first is presented in this article. The second, which includes items about α/β-NTCP/TCP values and reirradiation criteria, will be reported elsewhere. Results: Thirty-one radiation therapists from 29 radiation oncology departments answered the survey. 77.4-93.5% of responders used the basic formula from the linear-quadratic model and/or computer software for radiobiological calculations; 100% used lung (mostly V20, median <30%) and spinal cord constraints (mostly a median of physical maximum dose <45.5 Gy); and 90.3% used heart and oesophagus constraints (very heterogeneous parameters in both organs). Conclusions: Radiobiological considerations are clearly present in the planning process of radiotherapy of LC in Spain, with a high coincidence with the literature regarding lung and spinal cord constraints. The heterogeneity shown for oesophagus and heart results demonstrates the need for continuing investigation into the standardisation of clinical, dosimetric and radiobiologic aspects of the treatment of this cancer. © 2010 Feseo.


Bourgier C.,CNRS Gustave Roussy Institute | Calvo F.A.,Hospital General Universitario Gregorio Maranon | Marsiglia H.,Instituto Madrileno Of Oncologia | Marsiglia H.,CNRS Gustave Roussy Institute | Martin M.,Hospital General Universitario Gregorio Maranon
Clinical and Translational Oncology | Year: 2011

Radiochemotherapy is a standard approach in human solid tumours, with localised stage and radical treatment intention. In the early-intermediate stages of breast cancer model, neoadjuvant radiochemotherapy is an alternative to induction chemotherapy alone and might further impact the surgical technical treatment characteristics (a downsizing effect). In the era of targeted therapy and personalised treatment for breast cancer patients with initial localised disease, radiochemotherapy needs to be explored as a component of optimised local treatment to potentially improve relevant local results, such as breast conservation, breast cosmesis and individualised breast cancer radiochemotherapy response prediction. An overview of available literature data regarding neoadjuvant treatment including radiotherapy component is analysed and discussed.


Guerra J.L.L.,University of Texas M. D. Anderson Cancer Center | Guerra J.L.L.,Instituto Madrileno Of Oncologia | Guerra J.L.L.,Autonomous University of Barcelona | Gomez D.,University of Texas M. D. Anderson Cancer Center | And 7 more authors.
Radiotherapy and Oncology | Year: 2012

Purpose: We investigated the association between single nucleotide polymorphisms (SNPs) in the transforming growth factor β1 (TGFβ1) gene and the risk of radiation-induced esophageal toxicity (RE) in patients with non-small-cell lung cancer (NSCLC). Methods and materials: Ninety-seven NSCLC patients with available genomic DNA samples and mostly treated with intensity modulated radio(chemo)therapy from 2003 to 2006 were used as a test dataset and 101 NSCLC patients treated with 3-dimensional conformal radio(chemo)therapy from 1998 to 2002 were used as a validation set. We genotyped three SNPs of the TGFβ1 gene (rs1800469:C-509T, rs1800471:G915C, and rs1982073:T869C) by the polymerase chain reaction restriction fragment length polymorphism method. Results: In the test dataset, the CT/TT genotypes of TGFβ1 rs1800469:C-509T were associated with a statistically significant higher risk of RE grade ≥ 3 in univariate (P = 0.026) and multivariate analysis (P = 0.045) when compared with the CC genotype. These results were again observed in both univariate (P = 0.045) and multivariate (P = 0.023) analysis in the validation dataset. Conclusion: We found and validated that the TGFβ1 rs1800469:C-509T genotype is associated with severe RE. This response marker may be used for guiding therapy intensity in an individual patient, which would further the goal of individualized therapy. © 2012 Elsevier Ireland Ltd. All rights reserved.

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