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. 2011 Topics , Volume 21, Issues 1-4 January Early Stage Breast Cancer Lori Pierce, MD April Metabolic and Functional Imaging with Radiation Therapy James M. Balter, PhD July Rectal Cancer Brian Czito, MD, and Christopher Willett, MD October Liver Tumors (primary and metastatic) Laura Dawson, MD http://www.semradonc.com/?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. All rights reserved. Seminars in Radiation Oncology1053-4296222April 2012 © 2012 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.semradonc.com/article/PIIS1053429612000082/abstract?rss=yesEditorial Board10.1016/S1053-4296(12)00008-2Seminars in Radiation Oncology 22, 2 (2012)2012-04-01Seminars in Radiation Oncology2012-04-01222S1053-4296(11)X0006-1iiiihttp://www.semradonc.com/article/PIIS1053429612000021/abstract?rss=yesNormally, radiotherapy is given with the same dose to tumors of the same morphology and topology irrespective of individual parameters, although we are well aware that there must be some different characteristics, which in some patients may yield better tumor control and/or less morbidity. We have, therefore, with more or less eagerness pursued more specific prognostic and predictive parameters to identify tumors, which may need more or less aggressive treatment or in a similar way identify patients who may have more or less tolerance to such treatment.Introduction: Towards Predicting Outcome of Radiotherapy—At LastJens Overgaard, Harry Bartelink10.1016/j.semradonc.2012.01.001Seminars in Radiation Oncology 22, 2 (2012)2012-04-01Seminars in Radiation Oncology2012-04-01222S1053-4296(11)X0006-18790http://www.semradonc.com/article/PIIS105342961100141X/abstract?rss=yesRadiogenomics is the study of genetic variants, primarily single nucleotide polymorphisms, associated with the development of radiotherapy toxicity. The long-term goal of radiogenomics is to develop an assay capable of predicting which cancer patients are most likely to develop adverse effects after radiotherapy. The creation of such a predictive assay could help to personalize and optimize cancer treatment. This article reviews published radiogenomic studies and discusses the methodological issues surrounding this area of research. A glossary of radiogenomic terms is provided along with a list of recommended data that should be included in studies.Genome-Wide Association Studies and Prediction of Normal Tissue ToxicityCatharine M.L. West, Alison M. Dunning, Barry S. Rosenstein10.1016/j.semradonc.2011.12.007Seminars in Radiation Oncology 22, 2 (2012)2012-04-01Seminars in Radiation Oncology2012-04-01222S1053-4296(11)X0006-19199http://www.semradonc.com/article/PIIS1053429611001354/abstract?rss=yes Risk factors for local recurrence in breast cancer after breast conserving therapy (BCT) differ from those for local recurrence after mastectomy. To better guide optimal treatment of individual patients, it is desirable to identify patients at high risk for local recurrence. Several clinical and histopathologic factors, such as young age and presence of ductal carcinoma in situ, are known to be predictors for local recurrence after BCT. After mastectomy, lymph node status and tumor size are dominant risk factors for local recurrence. The results of recent expression profiling studies have explained differences in prognosis and risk for local recurrence and also explained response to different therapies (adjuvant systemic therapy and radiotherapy). Because of the variation in different subtypes of breast cancer and the difference in amount of tumor burden remaining after surgery, finding robust predictive profiles is complex. In this review, we describe the predictive and prognostic factors for local recurrence after mastectomy and BCT and also describe the role of radiosensitivity in local recurrence. Predictive Factors for Local Recurrence in Breast CancerFemke van der Leij, Paula H.M. Elkhuizen, Harry Bartelink, Marc J. van de Vijver10.1016/j.semradonc.2011.12.001Seminars in Radiation Oncology 22, 2 (2012)2012-04-01Seminars in Radiation Oncology2012-04-01222S1053-4296(11)X0006-1100107http://www.semradonc.com/article/PIIS1053429611001366/abstract?rss=yes Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Radiotherapy is a mainstay of treatment, either alone for early stage tumors or combined with chemotherapy for late stage tumors. An overall 5-year survival rate of around 50% for HNSCC demonstrates that treatment is often unsuccessful. Prediction of outcome is, therefore, aimed at sparing patients from ineffective and toxic treatments on the one hand, and indicating more successful treatment modalities on the other. Both functional and genetic assays have been developed to predict intrinsic radiosensitivity, hypoxia, and repopulation rate. Few, however, have shown consistent correlations with outcome across multiple studies. Messenger RNA and microRNA profiling show promise for predicting hypoxia, whereas epidermal growth factor receptor expression combined with other measures of tumor differentiation grade shows promise for predicting repopulation rate. Intrinsic radiosensitivity assays have not proven useful to date, although development of repair protein foci assays indicates promise from preclinical studies. Assays for cancer stem cell content have shown promise in several clinical studies. In addition, 2 assays showing robustness as predictors for outcome in HNSCC are human papilloma virus status and epidermal growth factor receptor expression. Neither these nor stem cell assays, however, can as yet reliably indicate alternative and better treatments for poor prognosis patients. It would be of great value to have assays that predict the benefit for an individual from combining new molecularly targeted agents with radiotherapy to increase response, in particular those that exploit tumor mutations to provide tumor specificity. Predictive assays are being developed for detecting defects in repair pathways for single- and double-strand DNA breaks, which should allow selection of drugs targeting the appropriate backup pathway, thus exploiting the concept of synthetic lethality. This is one of the most promising areas for prediction, both currently and in the future. Predicting Recurrence After Radiotherapy in Head and Neck CancerAdrian C. Begg10.1016/j.semradonc.2011.12.002Seminars in Radiation Oncology 22, 2 (2012)2012-04-01Seminars in Radiation Oncology2012-04-01222S1053-4296(11)X0006-1108118http://www.semradonc.com/article/PIIS1053429611001408/abstract?rss=yes Reliable methods for identification of hypoxia in radiotherapy-treated tumors have been a desirable aim in radiation oncology for decades. Hypoxia is a common feature of the microenvironment in solid tumors, and it is associated with increased aggressiveness, reduced therapeutic response, and a poorer clinical outcome. In head and neck squamous cell carcinomas, the negative effect of hypoxia on radiotherapeutic response can be counteracted and minimized by applying hypoxic modification to radiotherapy, which favors the clinical outcome after treatment. However, not all tumors are hypoxic, hence not all patients benefit from the addition of hypoxic modification. Therefore, predictive and clinically applicable methods for pretherapeutic hypoxic evaluation and categorization are needed. Hypoxia gene expression signatures are a developing strategy to approach this obstacle. This method has evolved along with the development of complementary DNA microarray analysis and classifies tumors in accordance to the expression of specific hypoxia-responsive genes in the tumor biopsy. Thus, tumors are classified and categorized in terms of the biological behavior to hypoxic conditions in the microenvironment. Until now, most of the developed hypoxia signatures have only been evaluated in terms of their prognostic impact; however, recently, a predictive impact for hypoxic modification of radiotherapy was verified. Here, we provide an overview of the hypoxic issue in radiotherapy and present the most promising hypoxia gene expression signatures developed to date. Hypoxia Gene Expression Signatures as Prognostic and Predictive Markers in Head and Neck RadiotherapyKasper Toustrup, Brita S. Sørensen, Jan Alsner, Jens Overgaard10.1016/j.semradonc.2011.12.006Seminars in Radiation Oncology 22, 2 (2012)2012-04-01Seminars in Radiation Oncology2012-04-01222S1053-4296(11)X0006-1119127http://www.semradonc.com/article/PIIS105342961100138X/abstract?rss=yes There has been a gradual change in the demographics of head and neck carcinoma. Although relatively uncommon, the incidence of oropharyngeal carcinoma has been increasing despite declining tobacco consumption and contrary to a diminishing incidence of cancers at other head and neck sites. It is now clear that the incidence of human papillomavirus (HPV)-associated oropharyngeal cancers is rising, likely as a consequence of changing life styles and sexual behaviors. Many studies have contributed to understanding the characteristics of HPV-related oropharyngeal carcinoma, which usually presents as nonkeratinizing squamous cell carcinoma of low to intermediate T-category and affects middle-aged white men, having higher socioeconomic status and no or brief history of tobacco consumption. The diagnosis of this distinct neoplastic entity can be firmly established by a combination of p16 immunohistochemical and in situ hybridization assays. Compared with the traditional smoking-associated head and neck squamous cell carcinoma, HPV-related oropharyngeal carcinoma has a favorable natural history and responds better to treatment. Consequently, patients with this cancer have better long-term survival than those with HPV-unrelated head and neck squamous cell carcinoma (eg, 5-year overall survival rate of >80% versus ∼40% for patients with stage III-IV tumors), and hence they are more likely to experience chronic therapy-induced morbidity. Therefore, changes in evaluation, staging, and treatment are needed for this patient group. However, attempts to change the treatment for HPV-associated oropharyngeal carcinoma should take place in a closely monitored clinical trial setting. In this article, we summarize the epidemiology, diagnosis, and clinical behavior of HPV-associated oropharyngeal carcinoma, with emphasis on prognostic and biomarker discovery aspects, and discuss briefly the current thoughts on changing the treatment paradigms aimed at reducing morbidity while preserving the high tumor control probability through well-coordinated prospective trials. Human Papillomavirus as a Marker of the Natural History and Response to Therapy of Head and Neck Squamous Cell CarcinomaKie Kian Ang, Erich M. Sturgis10.1016/j.semradonc.2011.12.004Seminars in Radiation Oncology 22, 2 (2012)2012-04-01Seminars in Radiation Oncology2012-04-01222S1053-4296(11)X0006-1128142http://www.semradonc.com/article/PIIS1053429611001433/abstract?rss=yes The addition of cisplatin-based chemotherapy to standard radiation therapy reduces the risk of recurrence and disease-related death rates from locally advanced cervical cancers by as much as 50%. However, the absolute gains are relatively small for patients with early tumors, many of whom would have been cured with radiation alone, and recurrence rates are still high for patients who have very large or advanced-stage tumors. As a result, there is a pressing need for more accurate predictors of radiocurability. A variety of types of biomarkers have been shown to correlate with cervical cancer response to radiation therapy. These include traditional clinical and morphologic predictors, non-molecular biomarkers, including hypoxia and fluorodeoxyglucose-positron emission tomography (FDG-PET) avidity, as well as molecular biomarkers, which include single-gene markers or array-based multigene predictors. Multi-gene predictors of response remain immature in cervical cancer, but studies thus far have paved the way for future studies to validate these findings. Methods will need to be standardized and markers will need to be validated on homogeneous patient populations and treatment approaches before they can become useful tools for clinical decision making. In addition, new biomarkers will be of major value only if they add to the predictive value of traditional clinical and morphologic predictors. Ultimately, the most useful biomarkers will identify patients who will benefit from specific molecularly targeted agents in addition to radiation therapy or perhaps identify patient who are at low risk for recurrence, for whom the dose of radiation or chemotherapy can be reduced. Biological Predictors of Cervical Cancer Response to Radiation TherapyAnn H. Klopp, Patricia J. Eifel10.1016/j.semradonc.2011.12.009Seminars in Radiation Oncology 22, 2 (2012)2012-04-01Seminars in Radiation Oncology2012-04-01222S1053-4296(11)X0006-1143150http://www.semradonc.com/article/PIIS1053429611001378/abstract?rss=yes Cancer stem cell research is one of the most thriving and competitive areas in oncology research because it has the potential to dramatically affect clinical outcomes. Led by progress in hematology, cancer stem cell research has now provided evidence to play an important role for solid cancers as well. Because radiotherapy is only second to surgery in terms of its curative potency, it is very important for radiation oncologists to learn whether progress in cancer stem cell biology can enable them to exploit this knowledge to help cure more patients suffering from cancer. The present article gives an overview about the challenges of the cancer stem cell concept and highlights some important phenomena that are under intense investigation, such as phenotypic plasticity of stemness and impact and dynamics of microenvironmental niches. We discuss the potential and limitations of current experimental and theragnostic tools and end up with an agenda for future research as outlook for translational possibilities in the clinic. Cancer Stem Cells as a Predictive Factor in RadiotherapyThomas B. Brunner, Leoni A. Kunz-Schughart, Philipp Grosse-Gehling, Michael Baumann10.1016/j.semradonc.2011.12.003Seminars in Radiation Oncology 22, 2 (2012)2012-04-01Seminars in Radiation Oncology2012-04-01222S1053-4296(11)X0006-1151174http://www.semradonc.com/article/PIIS1053429611001391/abstract?rss=yes The treatment of rectal cancer largely depends on disease stage at diagnosis, based on which patients can be classified as low, intermediate, or high risk. Prognostic and predictive markers, specific to each risk category, can be applied for optimal risk classification and subsequent treatment allocation. These markers are either histopathological, determined with imaging, or have a biomolecular background. This review provides an overview of the current status of treatment options and the use of prognostic and predictive markers in each risk category. An effort was made to identify those markers that are currently lacking in, but have the potential to improve, the clinical decision process by discussing the data from recent studies aimed at the development of new prognostic and predictive markers. At this moment, none of the markers studied has been proven to be of significant, independent value, justifying implementation in daily clinical practice. However, recent developments in imaging techniques and biomolecular research do show great potential. Prediction in Rectal CancerEliane C.M. Zeestraten, Peter J.K. Kuppen, Cornelis J.H. van de Velde, Corrie A.M. Marijnen10.1016/j.semradonc.2011.12.005Seminars in Radiation Oncology 22, 2 (2012)2012-04-01Seminars in Radiation Oncology2012-04-01222S1053-4296(11)X0006-1175183