The Role of Postmastectomy Radiation Therapy in Patients With Breast Cancer Responding to Neoadjuvant Chemotherapy
When surgery is the first line of breast cancer treatment, numerous randomized clinical trials and meta-analyses have demonstrated that postmastectomy radiation therapy (PMRT) improves locoregional control and survival for many women with axillary lymph node–positive disease. In contrast, there are no randomized data regarding the use of PMRT in women who receive neoadjuvant chemotherapy (NAC) first followed by mastectomy. This has led to controversy regarding which patient with breast cancer will benefit from PMRT after NAC, particularly in women with clinically node-positive axillary disease that responds well and ...
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: Jose G. Bazan, Julia R. White Source Type: research

Molecular Phenotype, Multigene Assays, and the Locoregional Management of Breast Cancer
Molecular profiling has revealed that breast cancer is not a single disease entity, but rather a class of heterogeneous subtypes, each with its own inherent biology and natural history. As a result, different treatment approaches have been optimized for the various subtypes and, in turn, the ability to identify subtypes has become a critical element in the management of breast cancer. Comprehensive transcriptional profiling studies have revealed at least 4 principal subtypes that, in practice, are often distinguished by immunohistochemical staining of the estrogen receptor (ER), progesterone receptor (PR), and HER2, along ...
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: Lior Z. Braunstein, Alphonse G. Taghian Source Type: research

Management of the Regional Lymph Nodes in Early-Stage Breast Cancer
The management of regional nodes in early-stage invasive breast cancer continues to evolve. Improved systemic therapy has contributed to better local regional control, and at the same time it has drawn more attention to its importance. Axillary dissections have decreased, in part because of the increased efficacy of systemic therapy, and also because adjuvant therapy decisions are increasingly driven by biologic characterization of the tumor rather than pathologic nodal information. The trend toward less axillary surgery and a shift toward increased reliance on systemic and radiation therapy to address nodal disease has cr...
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: Julia S. Wong, Laura E.G. Warren, Jennifer R. Bellon Source Type: research

Surgical Management of de novo Stage IV Breast Cancer
The natural history of stage IV breast cancer is changing, with diagnosis when the disease burden is lower and better drugs translating into longer survival. Nevertheless, a small but constant fraction of women present with de novo stage IV disease and an intact primary tumor. The management of the primary site in this setting has classically been determined by the presence of symptoms, but this approach has been questioned based on multiple retrospective reviews reported over the past decade that suggested a survival advantage for women whose intact primary tumor is resected. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: Seema Ahsan Khan Source Type: research

Novel and Highly Compressed Schedules for the Treatment of Breast Cancer
Our thinking about radiotherapy (RT) for early-stage breast cancer has evolved considerably over the last several years. Increasingly patients and physicians together are making the decision to use altered fractionation rather than standard 6-7 weeks of conventional whole breast treatment plus lumpectomy bed boost. Adjuvant hypofractionated whole breast irradiation is now viewed as a preferred strategy for many eligible women, and can be completed in 3-4 weeks. Adjuvant accelerated partial breast irradiation is another alternative that is typically delivered in 8-10 fractions over 4-5 days. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: Atif J. Khan, Stuti Ahlawat, Sharad Goyal Source Type: research

Introduction: The Changing Spectrum of Breast Cancer
Change is the process by which the future invades our lives. (Alvin Toffler) (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: David E. Wazer Source Type: research

Contemporary Breast Radiotherapy and Cardiac Toxicity
Long-term cardiac effects are an important component of survivorship after breast radiotherapy. The pathophysiology of cardiotoxicity, history of breast radiotherapy, current methods of cardiac avoidance, modern outcomes, context of historical outcomes, quantifying cardiac effects, and future directions are reviewed in this article. Radiation-induced oxidative stress induces proinflammatory cytokines and is a process that potentiates late effects of fibrosis and intimal proliferation in endothelial vasculature. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: Debra Nana Yeboa, Suzanne Buckley Evans Source Type: research

Breast Cancer Risk Assessment: Moving Beyond BRCA 1 and 2
The National Cancer Institute estimates that 12.3% of all women (about 1 in 8) would be diagnosed with breast cancer throughout their lifetime. In 2015, a projected 231,840 new cases are expected in the United States, accompanied by 40,290 deaths. Presently, breast cancer is responsible for 6.8% of all cancer deaths, and roughly 30% of all cancers in women. Since the discovery of the BRCA gene in 1994, efforts have been made to develop effective screening methods for breast cancer detection. Although the BRCA gene certainly opened the door to breast cancer genetics, a wide variety of new genes have recently been linked to ...
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: Jennifer Scalia-Wilbur, Bradley L. Colins, Richard T. Penson, Don S. Dizon Source Type: research

Advances in Medical Management of Early Stage and Advanced Breast Cancer: 2015
Standard management of early stage and advanced breast cancer has been improved over the past few years by knowledge gained about the biology of the disease, results from a number of eagerly anticipated clinical trials and the development of novel agents that offer our patients options for improved outcomes or reduced toxicity or both. This review highlights recent major developments affecting the systemic therapy of breast cancer, broken down by clinically relevant patient subgroups and disease stage, and briefly discusses some of the ongoing controversies in the treatment of breast cancer and promising therapies on the h...
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: Sabrina Witherby, Tina Rizack, Bachir J. Sakr, Robert D. Legare, William M. Sikov Source Type: research

Incorporating Imaging Into the Locoregional Management of Breast Cancer
Although some breast cancers present as palpable masses or with other clinical findings, many are detected at screening. Most screening is currently done with digital mammography, but high-risk patients or those with dense breast tissue may undergo additional screening examinations with magnetic resonance imaging or ultrasound. Additionally, digital breast tomosynthesis, contrast-enhanced mammography, and molecular breast imaging are newer technologies available at some sites. Optimal usage of breast imaging technologies remains controversial, both in screening and diagnostic settings following a new diagnosis of breast ca...
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: Ana P. Lourenco, Martha B. Mainiero Source Type: research

New Insights into the Surgical Management of Breast Cancer
William Halstead is considered by many as the father of modern breast surgery. He popularized the notion that breast cancer progresses in an orderly fashion and that appropriately timed radical surgery can interrupt this progression to save lives. This view dominated for nearly 100 years and still persists to one extent or another in the minds of physicians and patients alike. Rapid advances in breast cancer biology have highlighted the heterogeneity of breast cancer and paradigm-shifting clinical trials have successfully challenged prevailing wisdom to effect a seed change in breast cancer surgery. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - November 28, 2015 Category: Cancer & Oncology Authors: David M. Euhus Source Type: research

Predicting Radiotherapy Responses and Treatment Outcomes Through Analysis of Circulating Tumor DNA
Tumors continually shed DNA into the blood where it can be detected as circulating tumor DNA (ctDNA). Although this phenomenon has been recognized for decades, techniques that are sensitive and specific enough to robustly detect ctDNA have only become available recently. Quantification of ctDNA represents a new approach for cancer detection and disease burden quantification that has the potential to revolutionize response assessment and personalized treatment in radiation oncology. Analysis of ctDNA has many potential applications, including detection of minimal residual disease following radiotherapy, noninvasive tumor ge...
Source: Seminars in Radiation Oncology - September 15, 2015 Category: Cancer & Oncology Authors: Aadel A. Chaudhuri, Michael S. Binkley, Evan C. Osmundson, Ash A. Alizadeh, Maximilian Diehn Source Type: research

Quantitative Imaging in Radiation Oncology: An Emerging Science and Clinical Service
Radiation oncology has long required quantitative imaging approaches for the safe and effective delivery of radiation therapy. The past 10 years has seen a remarkable expansion in the variety of novel imaging signals and analyses that are starting to contribute to the prescription and design of the radiation treatment plan. These include a rapid increase in the use of magnetic resonance imaging, development of contrast-enhanced imaging techniques, integration of fluorinated deoxyglucose–positron emission tomography, evaluation of hypoxia imaging techniques, and numerous others. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - September 15, 2015 Category: Cancer & Oncology Authors: David Anthony Jaffray, Caroline Chung, Catherine Coolens, Warren Foltz, Harald Keller, Cynthia Menard, Michael Milosevic, Julia Publicover, Ivan Yeung Source Type: research

Radiotherapy in the Era of Precision Medicine
Current predictors of radiation response are largely limited to clinical and histopathologic parameters, and extensive systematic analyses of the correlation between radiation sensitivity and genomic parameters remain lacking. In the era of precision medicine, the lack of -omic determinants of radiation response has hindered the personalization of radiation delivery to the unique characteristics of each patient׳s cancer and impeded the discovery of new therapies that can be administered concurrently with radiation therapy. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - September 15, 2015 Category: Cancer & Oncology Authors: Brian Yard, Eui Kyu Chie, Drew J. Adams, Craig Peacock, Mohamed E. Abazeed Source Type: research

Hypoxia and Predicting Radiation Response
The results from many studies indicate that most solid tumors, regardless of site of origin, contain hypoxic regions. Experimental studies have demonstrated that, apart from the well-known protective effect of hypoxia on the radiation response of cells and tissues, hypoxic conditions can also result in modified gene expression patterns, causing (to a greater or lesser extent in different cell populations) genomic instability, increased invasive capacity, higher propensity to metastasize, enhanced stem cell properties, and ability to survive nutrient deprivation. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - September 15, 2015 Category: Cancer & Oncology Authors: Richard P. Hill, Robert G. Bristow, Anthony Fyles, Marianne Koritzinsky, Michael Milosevic, Bradly G. Wouters Source Type: research

Tailoring Adjuvant Radiation Therapy by Intraoperative Imaging to Detect Residual Cancer
For many solid cancers, radiation therapy is offered as an adjuvant to surgical resection to lower rates of local recurrence and improve survival. However, a subset of patients treated with surgery alone will not have a local recurrence. Currently, there is no way to accurately determine which patients have microscopic residual disease in the tumor bed after surgery and therefore are most likely to benefit from adjuvant radiation therapy. To address this problem, a number of technologies have been developed to try to improve margin assessment of resected tissue and to detect residual cancer in the tumor bed. (Source: Semin...
Source: Seminars in Radiation Oncology - September 15, 2015 Category: Cancer & Oncology Authors: Melodi J. Whitley, Ralph Weissleder, David G. Kirsch Source Type: research

The Prediction of Radiotherapy Toxicity Using Single Nucleotide Polymorphism−Based Models: A Step Toward Prevention
Radiotherapy is a mainstay of cancer treatment, used in either a curative or palliative manner to treat approximately 50% of patients with cancer. Normal tissue toxicity limits the doses used in standard radiation therapy protocols and impedes improvements in radiotherapy efficacy. Damage to surrounding normal tissues can produce reactions ranging from bothersome symptoms that negatively affect quality of life to severe life-threatening complications. Improved ways of predicting, before treatment, the risk for development of normal tissue toxicity may allow for more personalized treatment and reduce the incidence and sever...
Source: Seminars in Radiation Oncology - September 15, 2015 Category: Cancer & Oncology Authors: Sarah L. Kerns, Suman Kundu, Jung Hun Oh, Sandeep K. Singhal, Michelle Janelsins, Lois B. Travis, Joseph O. Deasy, A. Cecile J.E. Janssens, Harry Ostrer, Matthew Parliament, Nawaid Usmani, Barry S. Rosenstein Source Type: research

DNA Damage Response Assessments in Human Tumor Samples Provide Functional Biomarkers of Radiosensitivity
Predictive biomarkers are urgently needed for individualization of radiation therapy and treatment with radiosensitizing anticancer agents. Genomic profiling of human cancers provides us with unprecedented insight into the mutational landscape of genes directly or indirectly involved in the response to radiation-induced DNA damage. However, to what extent this wealth of structural information about the cancer genome produces biomarkers of sensitivity to radiation remains to be seen. Investigators are increasingly studying the subnuclear accumulation (ie, foci) of proteins in the DNA damage response (DDR), such as gamma-H2A...
Source: Seminars in Radiation Oncology - September 15, 2015 Category: Cancer & Oncology Authors: Henning Willers, Liliana Gheorghiu, Qi Liu, Jason A. Efstathiou, Lori J. Wirth, Mechthild Krause, Cläre von Neubeck Source Type: research

Patient-Derived Xenografts as a Model System for Radiation Research
The cancer literature is filled with promising preclinical studies demonstrating impressive efficacy for new therapeutics, yet translation of these approaches into clinical successes has been rare, indicating that current methods used to predict efficacy are suboptimal. The most likely reason for the limitation of these studies is the disconnect between preclinical models and cancers treated in the clinic. Specifically, most preclinical models are poor representations of human disease. Immortalized cancer cell lines that dominate the cancer literature may be, in a sense, “paper tigers” that have been selected b...
Source: Seminars in Radiation Oncology - September 15, 2015 Category: Cancer & Oncology Authors: Christopher D. Willey, Ashley N. Gilbert, Joshua C. Anderson, George Yancey Gillespie Source Type: research

Breast Cancer Stem Cell Correlates as Predicative Factors for Radiation Therapy
In today׳s era of personalized medicine, the use of radiation therapy for breast cancer is still tailored to the type of surgery and the stage of the cancer. The future of breast radiation oncology would hopefully entail selecting patients for whom there is a clear benefit for the use of radiation therapy. To get to this point we need reliable predictors of radiation response. Cancer stem cells have been correlated to radiation resistance and outcome for patients with breast cancer, and there is considerable interest in whether cancer stem cell markers or biologic surrogates may be predictive of response to radiation ther...
Source: Seminars in Radiation Oncology - September 15, 2015 Category: Cancer & Oncology Authors: Adam R. Wolfe, Wendy A. Woodward Source Type: research

Biomarkers for Predicting Radiation Response
Radiation therapy is planned according to an individual patient׳s anatomy. Radiation oncologists generally contour the tumor and design the clinical target volume using computed tomography (or magnetic resonance imaging) on a slice-by-slice basis every 1-3mm. Although the radiation field is customized for each individual patient, in most clinical settings the radiation dose selected and the estimated risk of a normal tissue complication is largely based on population averages for the likelihood of tumor control and as well as acute and late toxicity. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - September 15, 2015 Category: Cancer & Oncology Authors: David G. Kirsch Source Type: research

Recent Technical Advances and Indications for Radiation Therapy in Low-Grade Glioma
The use of radiotherapy in low-grade glioma has been a topic of controversy over the past 2 decades. Although earlier studies showed no overall survival benefit and no dose response, recent studies demonstrate a possible synergism between radiotherapy and chemotherapy. However, many questions remained unanswered regarding the proper management including the potential roles of biological imaging in treatment planning, the role of reirradiation after recurrence, the role of intensity-modulated radiation therapy and proton beam radiotherapy, and the proper choice of chemotherapy agents. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 5, 2015 Category: Cancer & Oncology Authors: Michael D. Chan Source Type: research

Advances in Magnetic Resonance Imaging and Positron Emission Tomography Imaging for Grading and Molecular Characterization of Glioma
This article highlights advances in magnetic resonance imaging (MRI), including diffusion-weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy, dynamic contrast-enhanced imaging, and perfusion MRI, as well as position emission tomography using various tracers including methyl-11C-l-methionine and O-(2-18F-fluoroethyl)-l-tyrosine. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 5, 2015 Category: Cancer & Oncology Authors: Caroline Chung, Ur Metser, Cynthia Ménard Source Type: research

Advances in Magnetic Resonance and Positron Emission Tomography Imaging: Assessing Response in the Treatment of Low-Grade Glioma
Following combined-modality therapy for the treatment of low-grade gliomas, the assessment of treatment response and the evaluation of disease progression are uniformly challenging. In this article, we review existing response criteria, and discuss the limitations of conventional magnetic resonance imaging to distinguish between progression and treatment effect. We review the data on advanced imaging techniques including positron emission tomography and functional magnetic resonance imaging, which may enhance the interpretation of posttreatment changes, and enable the earlier assessment of the efficacy and toxicity of ther...
Source: Seminars in Radiation Oncology - June 5, 2015 Category: Cancer & Oncology Authors: Michelle M. Kim, Theodore S. Lawrence, Yue Cao Source Type: research

Radiation Therapy Oncology Group 9802: Controversy or Consensus in the Treatment of Newly Diagnosed Low-Grade Glioma?
Treatment of newly diagnosed or suspected low-grade glioma (LGG) is one of the most controversial areas in neuro-oncology. The heterogeneity of these tumors, concern regarding morbidity of treatment, and absence of proven overall survival benefit from any known treatment have resulted in a lack of consensus regarding the timing and extent of surgery, timing of radiotherapy (RT), and role of chemotherapy. The long-term results of Radiation Therapy Oncology Group (RTOG) 9802, a phase III randomized trial comparing RT alone with RT and 6 cycles of adjuvant procarbazine, CCNU, vincristine (PCV), demonstrated an unprecedented 5...
Source: Seminars in Radiation Oncology - June 5, 2015 Category: Cancer & Oncology Authors: Nadia N. Laack, Jann N. Sarkaria, Jan C. Buckner Source Type: research

Neurocognitive Function Following Therapy for Low-Grade Gliomas
Low-grade gliomas (LGGs) are a heterogenous group of primary brain neoplasms that most commonly occur in children and young adults, characterized by a slow, indolent course and overall favorable prognosis. Standard therapies used to treat LGGs have included surgical resection, radiotherapy, chemotherapy, or a combination thereof. Given the anticipated long survival and typical young age of patients with LGG, the long-term sequelae of therapy require special attention, especially as they affect neurocognitive function and quality of life. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 5, 2015 Category: Cancer & Oncology Authors: Mary Frances McAleer, Paul D. Brown Source Type: research

Molecular Markers in Low-Grade Glioma—Toward Tumor Reclassification
Low-grade diffuse gliomas are a heterogeneous group of primary glial brain tumors with highly variable survival. Currently, patients with low-grade diffuse gliomas are stratified into risk subgroups by subjective histopathologic criteria with significant interobserver variability. Several key molecular signatures have emerged as diagnostic, prognostic, and predictor biomarkers for tumor classification and patient risk stratification. In this review, we discuss the effect of the most critical molecular alterations described in diffuse (IDH1/2, 1p/19q codeletion, ATRX, TERT, CIC, and FUBP1) and circumscribed (BRAF-KIAA1549, ...
Source: Seminars in Radiation Oncology - June 5, 2015 Category: Cancer & Oncology Authors: Adriana Olar, Erik P. Sulman Source Type: research

Advances in the Surgical Management of Low-Grade Glioma
Over the past 2 decades, extent of resection has emerged as a significant prognostic factor in patients with low-grade gliomas (LGGs). Greater extent of resection has been shown to improve overall survival, progression-free survival, and time to malignant transformation. The operative goal in most LGG cases is to maximize extent of resection, while avoiding postoperative neurologic deficits. Several advanced surgical techniques have been developed in an attempt to better achieve maximal safe resection. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 5, 2015 Category: Cancer & Oncology Authors: Todd Hollon, Shawn L. Hervey-Jumper, Oren Sagher, Daniel A. Orringer Source Type: research

Indications for Treatment: Is Observation or Chemotherapy Alone a Reasonable Approach in the Management of Low-Grade Gliomas?
The treatment of newly diagnosed low-grade gliomas remains controversial. Recently published results from the long-term follow-up of Radiation Therapy Oncology Group (RTOG) trial 9802 demonstrated medically meaningful and statistically significant survival prolongation by adding chemotherapy with procarbazine, lomustine (CCNU), and vincristine after radiotherapy (RT) vs RT alone for “high”-risk patients (median 13.3 vs 7.8 years, hazard ratio = 0.59, P = 0.03). However, in the 17 years since that trial was launched, there have been advances in the understanding of low-grade gliomas biology and patient heterogen...
Source: Seminars in Radiation Oncology - June 5, 2015 Category: Cancer & Oncology Authors: Lauren R. Schaff, Andrew B. Lassman Source Type: research

Clinical Management of Seizures in Patients With Low-Grade Glioma
Seizures, transient disruptions of normal brain electrical activity, are common for patients with low-grade glioma (LGG) and significantly affect quality of life. Up to 75% of patients with a LGG will have seizures in the course of their disease (compared with 1%-2% of the general population). Depending on the type of abnormal electrical activity, the functional implications of seizure can impact any domain, including mental status, sensation or strength. In most cases, either the seizure or the medications used to treat the seizure may contribute to cognitive and psychosocial difficulties of various degrees of severity. (...
Source: Seminars in Radiation Oncology - June 5, 2015 Category: Cancer & Oncology Authors: Anna F. Piotrowski, Jaishri Blakeley Source Type: research

Introduction
In this issue of Seminars in Radiation Oncology, we survey the recent advances in the biology and treatment of low-grade gliomas. Recent developments in the treatment of low-grade gliomas such as those that follow from the updates to the randomized clinical trial Radiation Therapy Oncology Group (RTOG) 98-021 are practice-changing. The following articles offer insight into the reasoning and the data in support of current treatment options, novel therapies, and future trends. In doing so, the articles highlight a common theme: the need for a multidisciplinary treatment approach to low-grade gliomas. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 5, 2015 Category: Cancer & Oncology Authors: Christina Tsien Source Type: research

International Patterns of Radiotherapy Practice for Non–Small Cell Lung Cancer
Radiotherapy is an important treatment modality for non–small cell lung cancer (NSCLC). There are models of radiotherapy utilization that estimate the proportion of patients with NSCLC who have an evidence-based indication for radiotherapy. These estimates range from 46%-68% for radiotherapy utilization at diagnosis and 64%-75% overall. However, actual radiotherapy utilization throughout much of the world is lower than this, ranging from 28%-53%, with the largest differences between actual and estimated radiotherapy utilization seen in stage III NSCLC. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: Shalini K. Vinod Source Type: research

Intensity-Modulated Radiotherapy, Not 3 Dimensional Conformal, Is the Preferred Technique for Treating Locally Advanced Lung Cancer
This article summarizes these strategies and reviews published findings supporting the safety and efficacy of IMRT for lung cancer. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: Joe Y. Chang Source Type: research

Superiority of Concomitant Chemoradiation Over Sequential Chemoradiation in Inoperable, Locally Advanced Non–Small Cell Lung Cancer: Challenges in the Selection of Appropriate Chemotherapy
Treatment of inoperable, locally advanced non–small cell lung cancer (LA-NSCLC) is challenging and requires a multidisciplinary approach considering both local therapy and systemic therapy. Based on the results from several phase III studies and 2 meta-analyses, the use of concomitant chemoradiation therapy (ChRT) could significantly improve overall survival and is considered the standard of care in LA-NSCLC with good performance status. Currently, no evidence has shown a significant survival benefit of third-generation regimens applied in combination with ChRT compared with second-generation regimens. (Source: Semin...
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: Nan Bi, Luhua Wang Source Type: research

Intensity-Modulated Radiotherapy, Not 3 Dimensional Conformal, Is the Preferred Technique for Treating Locally Advanced Disease With High-Dose Radiotherapy: The Argument Against
Intensity-modulated radiotherapy (IMRT) allows the delivery of high-dose radiotherapy to target volumes, while sparing adjacent normal tissues. This has been mooted as a method of treating larger and otherwise untreatable lung cancers or of escalating radiotherapy doses. The possibility of achieving these aims has been confirmed in many planning studies, but there is little supporting clinical data. No randomized trial has compared conformal and IMRT, few studies have reported the late outcomes of IMRT, and there is no evidence for improved control of lung cancer with increased radiation dose. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: Allan Price Source Type: research

To SABR or Not to SABR? Indications and Contraindications for Stereotactic Ablative Radiotherapy in the Treatment of Early-Stage, Oligometastatic, or Oligoprogressive Non–Small Cell Lung Cancer
Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for early-stage non–small cell lung cancer. Although direct comparisons from randomized trials are not available, rates of both primary tumor control and distant metastasis are similar between SABR and surgery. Overall survival is lower after SABR compared with surgery, largely reflecting that a primary selection criterion for SABR has been medical inoperability because of decreased cardiopulmonary function and other comorbidities that lead to decreased survival independent of non–small cell lung cancer. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: David Benjamin Shultz, Maximilian Diehn, Billy W. Loo Tags: Invited Review Source Type: research

Hypoxia as a Cause of Treatment Failure in Non–Small Cell Carcinoma of the Lung
Hypoxia is an important factor in tumor biology and is both a predictive and a prognostic factor in non–small cell lung cancer. The negative effect of low oxygenation on radiation therapy effect has been known for decades, but more recent research has emphasized that hypoxia also has a profound effect on a tumor’s aggression and metastatic propensity. In this review, current knowledge on both these aspects of treatment failure in NSCLC due to hypoxia has been discussed, along with a presentation of modern methods for hypoxia measurement and current therapeutical interventions to circumvent the negative effect o...
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: Odd Terje Brustugun Source Type: research

The Evolving Role of Molecular Imaging in Non–Small Cell Lung Cancer Radiotherapy
Molecular imaging with positron emission tomography (PET) has dramatically changed the management of patients with lung cancer who are treated with radiotherapy. Uptake of the most widely used PET radiopharmaceutical 18F-fluorodeoxyglucose identifies lung nodules or intrathoracic lymph nodes as likely to be malignant and frequently identifies previously unsuspected sites of malignant disease outside the thorax. Patients with non–small cell lung cancer, especially those with apparently more advanced locoregional disease to start with, are often upstaged, and this has a profound effect on their subsequent management. (...
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: Michael MacManus, Sarah Everitt, Rodney J. Hicks Source Type: research

Accelerated Repopulation as a Cause of Radiation Treatment Failure in Non–Small Cell Lung Cancer: Review of Current Data and Future Clinical Strategies
Despite convincing evidence that the principles of accelerated repopulation would open up additional therapeutic opportunities in the treatment of advanced-stage non–small cell lung cancer, this strategy has been generally underexplored. The implementation of accelerated radiotherapy schedules has been hampered by logistical barriers, concerns about acute toxicity, and the prioritization of integrating concurrent chemotherapy into the standard treatment platform. At present, it is unclear to what extent accelerated fractionation will influence future treatment paradigms in non–small cell lung cancer, although t...
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: Sue S. Yom Source Type: research

Nondosimetric Risk Factors for Radiation-Induced Lung Toxicity
The decision to administer a radical course of radiotherapy (RT) is largely influenced by the dose-volume metrics of the treatment plan, but what are the patient-related and other factors that may independently increase the risk of radiation lung toxicity? Poor pulmonary function has been regarded as a risk factor and a relative contraindication for patients undergoing radical RT, but recent evidence suggests that patients with poor spirometry results may tolerate conventional or high-dose RT as well as, if not better than, patients with normal function. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: Feng-Ming (Spring) Kong, Shulian Wang Source Type: research

Erratum to “New Considerations in Radiation Treatment Planning for Brain Tumors: Neural Progenitor Cell-Containing Niches” Semin Radiat Oncol 24:265-272, 2014
Figure 1 in the above-referenced article was published without an acknowledgment in error. The figure should have been credited as follows: © 2006 MediVisuals Inc. Reprinted with permission from Barani IJ, Benedict SH, Lin PS, “Neural stem cells: implications for the conventional radiotherapy of central nervous system malignancies,” Int J Radiat Oncol Biol Phys 68(2):324-333, 2007. We regret the omission. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: Carmen Kut, Kristin Janson Redmond Source Type: research

Curing Non–Small Cell Lung Cancer With Radiotherapy: No Longer an Oxymoron
A quarter of a century has now elapsed since Johnson et al1 published an article with the dispiriting title “Thoracic radiotherapy does not prolong survival in patients with locally advanced, unresectable non–small cell lung cancer.” This was a report of a randomized trial comparing “modern megavoltage radiotherapy” (60Gy in 30 fractions) vs the same radiotherapy plus vindesine vs vindesine alone. The results were indeed disappointing, with median survivals of 8.6, 9.4, and 10.1 months and 5-year survivals of 3%, 3%, and 1% in the 3 arms. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: David Ball Source Type: research

Molecular Determinants of Radiation Response in Non–Small Cell Lung Cancer
Non–small cell lung cancers are now recognized to contain considerable heterogeneity and molecular diversity. Substantial progress has been made regarding molecular determinants of response to targeted agents in advanced lung cancer, and recent findings have revealed subsets of patients with driver mutations that respond rapidly to selective inhibitors. In addition, new approaches to disrupting DNA repair and inflammation and activation of the immune system are being explored. A key question in the field is whether therapeutic multimodality options incorporating radiation therapy can capitalize on the gains made in s...
Source: Seminars in Radiation Oncology - March 14, 2015 Category: Cancer & Oncology Authors: Sue S. Yom, Maximilian Diehn, David Raben Source Type: research

Introduction
This issue of Seminars in Radiation Oncology focuses on the emerging research that encompasses the effects of ionizing radiation (IR) on the immune system. Although the finding that the degree of immunocompetence of the host influenced the response to radiotherapy dates back 35 years,1 it is only in the past 10 years that investigators have concentrated on studying the mechanisms behind these effects of radiation. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - December 5, 2014 Category: Cancer & Oncology Authors: Silvia C. Formenti Source Type: research

Combination Regimens of Radiation Therapy and Therapeutic Cancer Vaccines: Mechanisms and Opportunities
Radiation therapy (RT) is widely used with curative or palliative intent in the clinical management of multiple cancers. Although mainly aimed at direct tumor cell killing, mounting evidence suggests that radiation can alter the tumor to become an immunostimulatory milieu. Data suggest that the immunogenic effects of radiation can be exploited to promote synergistic antitumor effects in combination with immunotherapeutic agents. We review concepts associated with the immunogenic consequences of RT and highlight how preclinical findings are translating into clinical benefit for patients receiving combination regimens of RT ...
Source: Seminars in Radiation Oncology - December 5, 2014 Category: Cancer & Oncology Authors: Charlie Garnett-Benson, James W. Hodge, Sofia R. Gameiro Source Type: research

Current Clinical Trials Testing Combinations of Immunotherapy and Radiation
Preclinical evidence of successful combinations of ionizing radiation with immunotherapy has inspired testing the translation of these results to the clinic. Interestingly, the preclinical work has consistently predicted the responses encountered in clinical trials. The first example came from a proof-of-principle trial started in 2001 that tested the concept that growth factors acting on antigen-presenting cells improve presentation of tumor antigens released by radiation and induce an abscopal effect. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - December 5, 2014 Category: Cancer & Oncology Authors: Marka Crittenden, Holbrook Kohrt, Ronald Levy, Jennifer Jones, Kevin Camphausen, Adam Dicker, Sandra Demaria, Silvia Formenti Source Type: research

Combination of Radiotherapy and Immune Checkpoint Inhibitors
The ability of ionizing radiation to cause cell death and inflammatory reactions has been known since the beginning of its therapeutic use in oncology. However, only recently this property of radiation has attracted the attention of immunologists seeking to induce or improve antitumor immunity. As immune checkpoint inhibitors are becoming mainstream cancer treatments, radiation oncologists have begun to observe unexpected out-of-the-field (abscopal) responses in patients receiving radiation therapy during immunotherapy. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - December 5, 2014 Category: Cancer & Oncology Authors: Karsten A. Pilones, Claire Vanpouille-Box, Sandra Demaria Source Type: research

Radiotherapy and Immunogenic Cell Death
Advances in understanding the mechanisms that underlie the interplay between radiation-invoked immune responses and tumor regression are underway. Emerging applications of local radiotherapy as an immunologic adjuvant have provided radiation oncologists with a method for converting malignant cells into endogenous anticancer vaccines. The dispersion of radiotherapy-induced immune-stimulating tumor antigens released from dying tumor cells into the surrounding milieu (known as immunogenic cell death, Fig. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - December 5, 2014 Category: Cancer & Oncology Authors: Encouse B. Golden, Lionel Apetoh Source Type: research

Radiotherapy and Toll-Like Receptor Agonists
The clinical successes of CTLA4 and PD-1 immune checkpoint blockade in aggressive malignancies such as metastatic melanoma and non–small cell lung carcinoma inaugurate a new era in oncology. Indeed, as opposed to tumor-targeted therapies, it is now clear that immune-targeted therapies designed to enhance the antitumor immune response are a relevant strategy to obtain long-term tumor responses. Interestingly, the study of tumor cell death biology has recently revealed that part of radiotherapy efficacy relies on its ability to trigger an immune response against tumor cells. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - December 5, 2014 Category: Cancer & Oncology Authors: Aurelien Marabelle, Alex Filatenkov, Idit Sagiv-Barfi, Holbrook Kohrt Source Type: research

Radiation and Inflammation
The immune system has the power to modulate the expression of radiation-induced normal and tumor tissue damage. On the one hand, it can contribute to cancer cure, and on the other hand, it can influence acute and late radiation side effects, which in many ways resemble acute and chronic inflammatory disease states. The way radiation-induced inflammation feeds into adaptive antigen-specific immune responses adds another dimension to the tumor-host cross talk during radiation therapy and to possible radiation-driven autoimmune responses. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - December 5, 2014 Category: Cancer & Oncology Authors: Dörthe Schaue, Ewa D. Micewicz, Josephine A. Ratikan, Michael W. Xie, Genhong Cheng, William H. McBride Source Type: research