Papers by Luis Renato Garay Fajardo
Radiation Research, 2012
Radiation-induced heart disease (RIHD) is a serious side effect of radiotherapy for intrathoracic... more Radiation-induced heart disease (RIHD) is a serious side effect of radiotherapy for intrathoracic and chest wall tumors. The threshold dose for development of clinically significant RIHD is believed to be lower than previously assumed. Therefore, research into mechanisms of RIHD has gained substantial momentum. RIHD becomes clinically apparent ten to fifteen years after radiation exposure. Chronic manifestations of RIHD include accelerated atherosclerosis, cardiomyopathy, and valve abnormalities. Reducing exposure of the heart during radiotherapy is the only known method of preventing RIHD, and there are no approaches to reverse RIHD once it occurs. We use a combination of pharmacological and genetic animal models to determine biological mechanisms of RIHD. Major technological advances in small animal research have made this type of study more valuable. The long-term goal of this work is to identify targets for intervention in RIHD, thereby enhancing the efficacy and safety of thoracic radiotherapy. It is truly a great honor to receive the Radiation Research Society's 2011 Michael Fry Award, which recognizes the contributions of a junior investigator to the field of radiation research. The main focus of my research has always been radiation-induced heart disease (RIHD). This side effect of radiation therapy captured my attention both as a clinical problem and from a radiation biology standpoint. Here, I am very pleased to have the opportunity to present and describe this line of research, as I hope to convey to you my fascination with it. Radiation-induced heart disease is a long-term side effect of radiotherapy of thoracic and chest wall tumors when all or part of the heart is exposed to radiation. For instance, RIHD can occur among survivors of Hodgkin's disease (1,2) or breast cancer (3-5) because radiation therapy fields for those patients can encompass the heart. Manifestations of RIHD include accelerated atherosclerosis, pericardial and myocardial fibrosis, conduction abnormalities, and injury to cardiac valves (6, 7). Both incidence and severity of the disease increase with higher radiation dose, larger volume exposed, younger age at time of exposure, and greater time elapsed since treatment. From a clinical perspective, the only approach to reduce late complications in the heart is through efforts to reduce cardiac exposure during therapy. Indeed, radiotherapy has undergone many such improvements over the last decades. Nonetheless, recent studies indicate that despite safety advances in radiotherapy some patients with Hodgkin's disease, lung, esophageal or proximal gastric cancers still receive either a high dose of radiation to a small part of the heart or a low dose to the whole heart (8-13). In addition, there is increasing use of concomitant therapies, with the consequences of many combinations yet to be determined. While certain cardio-toxic
International Journal of Radiation Oncology*Biology*Physics, 2010
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 7... more Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 76; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2009.09.064; PII: S0360-3016(09)03399-9; Copyright (c) 2010 Elsevier Science BV, Amsterdam, The ...
Critical Reviews in Oncology/Hematology, 2003
As the number of cancer survivors grows because of advances in therapy, it has become more import... more As the number of cancer survivors grows because of advances in therapy, it has become more important to understand the longterm complications of these treatments. This article presents the current knowledge of adverse cardiovascular effects of radiotherapy to the chest. Emphasis is on clinical presentations, recommendations for follow-up, and treatment of patients previously exposed to irradiation. Medline TM literature searches were performed, and abstracts related to this topic from oncology and cardiology meetings were reviewed. Potential adverse effects of mediastinal irradiation are numerous and can include coronary artery disease, pericarditis, cardiomyopathy, valvular disease and conduction abnormalities. Damage appears to be related to dose, volume and technique of chest irradiation. Effects may initially present as subclinical abnormalities on screening tests or as catastrophic clinical events. Estimates of relative risk of fatal cardiovascular events after mediastinal irradiation for Hodgkin's disease ranges between 2.2 and 7.2 and after irradiation for left-sided breast cancer from 1.0 to 2.2. Risk is life long, and absolute risk appears to increase with length of time since exposure. Radiation-associated cardiovascular toxicity may in fact be progressive. Long-term cardiac follow-up of these patients is therefore essential, and the range of appropriate cardiac screening is discussed, although no specific, evidencebased screening regimen was found in the literature.
American Heart Journal, 1992
American Journal of Clinical Oncology, 1982
We have previously presented a histopathological grading scheme for thermal damage in normal porc... more We have previously presented a histopathological grading scheme for thermal damage in normal porcine adipose and skeletal muscle tissues. Here we have used this scheme to assess the heat sensitivity of these tissues, and evaluate the protective benefit of thermotolerance as induced by a prior thermal exposure. Tissues were exposed to temperatures rang ing from 40-50°for 30 min. Half of all sites also received a thermal exposure of 41.0-43.0°4 hr earlier. Biopsies for histological evaluation were obtained at 18 to 24 hr ("acute") and at 28 to 31 days ("chronic") following treatment. Only mild acute injury was seen in the early samples, following either single or double heat exposures, at all temperature levels. Minimal chronic damage was also seen in the late samples following single exposures of 45°or less. Higher single exposures caused im portant chronic lesions, the severity of which was dose depend ent. Regions that had received the earlier conditioning thermal exposure showed a significant protection against the subsequent thermal exposure. In such regions, mean (chronic) pathology scores were reduced by 76 to 86% over the temperature range 45-48°. The degree of acute damage failed to predict the degree of chronic damage. Overall, induction of thermotolerance pro vided an advantage of 2°or more in normal tissue protection.
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Papers by Luis Renato Garay Fajardo