Seminars in Radiation Oncology RSS feed: Current Issue. Each issue of Seminars in Radiation Oncology is compiled by a guest editor to address a specific topic in the specialty, presenting definitive information on areas of rapid change and development. A significant number of articles report new scientific information. Topics covered include tumor biology, diagnosis, medical and surgical management of the patient, and new technologies. Seminars in Radiation Oncology has an Impact Factor of 4.312 and is ranked 10th of 90 journals in Radiology, Nuclear Medicine & Medical Imaging category and 38th of 141 in Oncology category on the 2009 Journal Citation Reports®, published by Thomson Reuters. 2010 Topics , Volume 20, Issues 1-4 January Pediatric Cancers and Survivorship Sandy Constine, MD April Adaptive Radiation Therapy Di Yan, PhD, MD July Non-Small Cell Lung Cancer Stephen Hahn, MD October Targeted Biologics and Radiation Therapy Robert Bristow, MDhttp://www.semradonc.com/?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. Seminars in Radiation Oncology1053-4296203July 2010 © 2010 Published by Elsevier Inc. healthpermissions@elsevier.comhttp://www.semradonc.com/article/PIIS1053429610000093/abstract?rss=yesOut, out, brief candle!Life's but a walking shadow, a poor playerThat struts and frets his hour upon the stageAnd then is heard no more; it is a taleTold by an idiot, full of sound and fury,Signifying nothing (Macbeth Act V, Scene V, William Shakespeare)Introduction: Non–Small-Cell Lung Cancer and Pleural Malignancies: The End of the Era of Therapeutic Nihilism?Ramesh Rengan, Stephen M. Hahn10.1016/j.semradonc.2010.01.001Seminars in Radiation Oncology 20, 3 (2010)2010-07-01Seminars in Radiation Oncology2010-07-01203S1053-4296(10)X0003-0147148http://www.semradonc.com/article/PIIS105342961000010X/abstract?rss=yesThe recently developed ability to interrogate genome-wide data arrays has provided invaluable insights into the molecular pathogenesis of lung cancer. These data have also provided information for developing targeted therapy in lung cancer patients based on the identification of cancer-specific vulnerabilities and set the stage for molecular biomarkers that provide information on clinical outcome and response to treatment. In addition, there are now large panels of lung cancer cell lines, both non–small-cell lung cancer and small-cell lung cancer, that have distinct chemotherapy and radiation response phenotypes. We anticipate that the integration of molecular data with therapy response data will allow for the generation of biomarker signatures that predict response to therapy. These signatures will need to be validated in clinical studies, at first retrospective analyses and then prospective clinical trials, to show that the use of these biomarkers can aid in predicting patient outcomes (eg, in the case of radiation therapy for local control and survival). This review highlights recent advances in molecular profiling of tumor responses to radiotherapy and identifies challenges and opportunities in developing molecular biomarker signatures for predicting radiation response for individual patients with lung cancer.Radiogenomics Predicting Tumor Responses to Radiotherapy in Lung CancerAmit K. Das, Marcus H. Bell, Chaitanya S. Nirodi, Michael D. Story, John D. Minna10.1016/j.semradonc.2010.01.002Seminars in Radiation Oncology 20, 3 (2010)2010-07-01Seminars in Radiation Oncology2010-07-01203S1053-4296(10)X0003-0149155http://www.semradonc.com/article/PIIS1053429610000111/abstract?rss=yesThe tumor microenvironment (TME) of NSCLC is heterogeneous with variable blood flow through leaky immature vessels resulting in regions of acidosis and hypoxia. Hypoxia has been documented in NSCLC directly by polarographic needle electrodes and indirectly by assessing tissue and plasma hypoxia markers. In general, elevated expression of these markers portends poorer outcomes in NSCLC. Impaired vascularity and hypoxia can lead to increased metastasis and treatment resistance. Compounds that directly target hypoxic cells such as tirapazamine have been tested in clinical trials for NSCLC with mixed results. Preclinical data, however, suggest other ways of exploiting the abnormal TME in NSCLC for therapeutic gain. The inhibition of hypoxia-inducible factor-1α or vascular endothelial growth factor may increase local control after radiation. Inhibitors of the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway, such as erlotinib or PI-103, may “normalize” tumor vessels, allowing for increased chemotherapy delivery or improved oxygenation and radiation response. To select patients who may respond to these therapies and to evaluate the effects of these agents, a noninvasive means of imaging the TME is critical. Presently, there are several promising modalities to image hypoxia and the tumor vasculature; these include dynamic perfusion imaging and positron emission tomography scanning with radiolabled nitroimidazoles.The Tumor Microenvironment in Non–Small-Cell Lung CancerEdward E. Graves, Amit Maity, Quynh-Thu Le10.1016/j.semradonc.2010.01.003Seminars in Radiation Oncology 20, 3 (2010)2010-07-01Seminars in Radiation Oncology2010-07-01203S1053-4296(10)X0003-0156163http://www.semradonc.com/article/PIIS1053429610000147/abstract?rss=yesNew imaging technologies have advanced our ability to treat lung cancers through enhanced and extended visualization of the tumor as well as patient and treatment response. Image guidance can reduce uncertainty by increasing precision and accuracy through improved patient selection, target delineation, and improved knowledge of nodal involvement. Conformal imaging-based radiotherapy (RT) can allow dose escalation. In the future, imaging may allow adaptive RT to be exploited in selected patients, especially those with large geometric changes occurring during RT. Furthermore, functional imaging, although in its infancy, has the potential to significantly improve RT, from RT planning and delivery to outcome assessment.Image Guidance in Non–Small Cell Lung CancerB.C. John Cho, Andrea Bezjak, Laura A. Dawson10.1016/j.semradonc.2010.01.006Seminars in Radiation Oncology 20, 3 (2010)2010-07-01Seminars in Radiation Oncology2010-07-01203S1053-4296(10)X0003-0164170http://www.semradonc.com/article/PIIS1053429610000135/abstract?rss=yesOne of the many challenges of lung cancer radiotherapy is conforming the radiation dose to the target because of tumor/organ motion and the need to spare surrounding critical structures. Evolving radiotherapy technologies, such as 4-dimensional image-based motion management, daily on-board imaging, and adaptive radiotherapy, have enabled us to improve the therapeutic index of radiation therapy for lung cancer by permitting the design of personalized treatments that deliver adequate doses conforming to the target while sparing the surrounding critical normal tissues. Four-dimensional computed tomography image-based motion management provides an opportunity to individualize target motion margins and reduce the risk of a geographic target miss. Daily on-board imaging and adaptive radiotherapy reduce setup and motion/anatomy uncertainties over the course of radiotherapy. These achievements in image guidance have permitted the implementation in lung cancer patients of highly conformal treatment delivery techniques that are exquisitely sensitive to organ motion and anatomic change, such as intensity-modulated radiation therapy, stereotactic body radiation therapy, and proton therapy. More clinical studies are needed to further optimize conformal radiotherapy using individualized treatment adaptations based on changes in anatomy and tumor motion during the course of radiotherapy and using functional and biological imaging to selectively escalate doses to radioresistant subregions within the tumor.Improving Radiation Conformality in the Treatment of Non–Small-Cell Lung CancerJoe Y. Chang, James D. Cox10.1016/j.semradonc.2010.01.005Seminars in Radiation Oncology 20, 3 (2010)2010-07-01Seminars in Radiation Oncology2010-07-01203S1053-4296(10)X0003-0171177http://www.semradonc.com/article/PIIS1053429610000123/abstract?rss=yesFor medically operable patients with stage I non–small-cell lung cancer (NSCLC), lobectomy or pneumonectomy remains the standard of care. The utility of radiotherapy or chemotherapy after major pulmonary resection remains unproven, though clinical and biological models may identify subgroups most likely to benefit. Limited resection results in higher rates of local failure for all but the most highly selected patients, though brachytherapy may reduce this risk. In medically inoperable patients, conventional radiotherapy results in control rates less than half of that achieved by surgery. Dose escalation and hypofractionation are technically feasible with modern planning and delivery, and appear to improve control rates compared with conventional radiotherapy. Stereotactic body radiotherapy represents a major advance for the treatment of stage I NSCLC, with early reports documenting excellent control rates and a low risk of severe toxicity. In this review we address each of these points, with particular emphasis on recent or ongoing prospective trials.The Treatment of Early-Stage DiseaseClifford G. Robinson, Jeffrey D. Bradley10.1016/j.semradonc.2010.01.004Seminars in Radiation Oncology 20, 3 (2010)2010-07-01Seminars in Radiation Oncology2010-07-01203S1053-4296(10)X0003-0178185http://www.semradonc.com/article/PIIS1053429610000159/abstract?rss=yesWith 40,000 to 50,000 patients diagnosed annually, stage III lung cancer represents approximately one third of all non–small-cell lung cancer cases. It is a heterogeneous disease stage encompassing stage IIIa, for which surgery in combination with chemotherapy and/or radiation therapy represents a treatment strategy for select patients, and stage IIIb, for which chemoradiation represents the prevailing standard of care. Overcoming unacceptably high rates of intrathoracic tumor failures remains a central obstacle. Current clinical trial efforts focus on targeted therapies, new chemotherapy regimens, dose-escalated radiation therapy, and improvements in radiation therapy treatment delivery.Combined Modality Therapy for Stage III Non–Small-Cell Lung CancerCynthia S. Anderson, Walter J. Curran10.1016/j.semradonc.2010.01.007Seminars in Radiation Oncology 20, 3 (2010)2010-07-01Seminars in Radiation Oncology2010-07-01203S1053-4296(10)X0003-0186191http://www.semradonc.com/article/PIIS1053429610000160/abstract?rss=yesRadiation therapy can increase local control and potentially improve survival in patients who have had resection for lung cancer. However, radiation therapy also has the potential to cause serious toxicity and should not be indiscriminately delivered. The PORT meta-analysis clearly illustrated the potential toxic effects of postoperative radiotherapy (PORT). Modern three-dimensional radiation treatment planning facilitates the design of treatment fields that more conformally treat the site(s) at risk, and this appears, based on limited data, to improve the therapeutic ratio of PORT. Moreover, systemic and local therapies are likely synergistic, and thus improvements in systemic staging and treatment may increase the ability of local therapies to improve overall survival. Therefore, a reassessment of the utility of postoperative radiation therapy using limited fields and modern techniques is warranted.Current Status of Postoperative Radiation for Non–Small-Cell Lung CancerMert Saynak, Daniel S. Higginson, David E. Morris, Lawrence B. Marks10.1016/j.semradonc.2010.01.008Seminars in Radiation Oncology 20, 3 (2010)2010-07-01Seminars in Radiation Oncology2010-07-01203S1053-4296(10)X0003-0192200http://www.semradonc.com/article/PIIS1053429610000184/abstract?rss=yesThe goal of radiation therapy is to reduce or eliminate tumor burden while sparing normal tissues from long-term injury. Thoracic radiation presents a unique challenge because of the inherent sensitivity of normal lung tissue to radiation. Damage to normal lung tissue presents a major obstacle in the treatment of individuals. To overcome this problem, a number of strategies are being used, including the modulation of dose volume, the use of image-guided radiotherapy, and the use of agents designed to reduce lung injury from radiation. Herein we discuss our current knowledge of the molecular and cellular events that occur after radiation therapy, the clinical manifestations of radiation-induced lung injury, current strategies to minimize lung injury, and recent experimental methods to reduce lung injury and their potential for translation into the clinic.Radiation Pulmonary Toxicity: From Mechanisms to ManagementPaul R. Graves, Farzan Siddiqui, Mitchell S. Anscher, Benjamin Movsas10.1016/j.semradonc.2010.01.010Seminars in Radiation Oncology 20, 3 (2010)2010-07-01Seminars in Radiation Oncology2010-07-01203S1053-4296(10)X0003-0201207http://www.semradonc.com/article/PIIS1053429610000172/abstract?rss=yesPleural malignancies, primary or metastatic, portend a grim prognosis. In addition to the serious oncologic implications of a pleural malignancy, these tumors can be highly symptomatic. A malignant pleural effusion can cause dyspnea, secondary to lung compression, or even tension physiology from a hydrothorax under pressure. The need to palliate these effusions is a seemingly straightforward clinical scenario, but with nuances that can result in disastrous complications for the patient if not attended to appropriately. Solid pleural malignancies can cause great pain from chest wall invasion or can cause a myriad of morbid symptoms because of the invasion of thoracic structures, such as the heart, lungs, or esophagus. This article reviews pleural malignancies, the purely palliative treatments, and the treatments that are performed with definitive (curative) intent.Pleural MalignanciesJoseph S. Friedberg, Keith A. Cengel10.1016/j.semradonc.2010.01.009Seminars in Radiation Oncology 20, 3 (2010)2010-07-01Seminars in Radiation Oncology2010-07-01203S1053-4296(10)X0003-0208214