Myeloid-Derived Cells in Tumors: Effects of Radiation
The discrepancy between the in vitro and in vivo response to radiation is readily explained by the fact that tumors do not exist independently of the host organism; cancer cells grow in the context of a complex microenvironment composed of stromal cells, vasculature, and elements of the immune system. As the antitumor effect of radiotherapy depends in part on the immune system, and myeloid-derived cells in the tumor microenvironment modulate the immune response to tumors, it follows that understanding the effect of radiation on myeloid cells in the tumor is likely to be essential for comprehending the antitumor effects of ...
Source: Seminars in Radiation Oncology - December 5, 2014 Category: Cancer & Oncology Authors: Ralph E. Vatner, Silvia C. Formenti Source Type: research

The Immunology of Ablative Radiation
Radiation has been a staple of cancer therapy since the early 20th century and is implemented in nearly half of current cancer treatment plans. Originally, the genotoxic function of radiation led to a focus on damage and repair pathways associated with deoxyribonucleic acid as important therapeutic targets to augment radiation efficacy. However, in recent decades, the participation of endogenous immune responses in modifying radiation effects have been widely documented and exploited in both preclinical and clinical settings. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - December 5, 2014 Category: Cancer & Oncology Authors: Byron Burnette, Ralph R. Weichselbaum Source Type: research

Recurrent Malignant Gliomas
Abstract: In almost all patients, malignant glioma recurs following initial treatment with maximal safe resection, conformal radiotherapy, and temozolomide. This review describes the many options for treatment of recurrent malignant gliomas, including reoperation, alternating electric field therapy, chemotherapy, stereotactic radiotherapy or radiosurgery, or some combination of these modalities, presenting the evidence for each approach. No standard of care has been established, though the antiangiogenic agent, bevacizumab; stereotactic radiotherapy or radiosurgery; and, perhaps, combined treatment with these 2 modalities ...
Source: Seminars in Radiation Oncology - September 15, 2014 Category: Cancer & Oncology Authors: John P. Kirkpatrick, John H. Sampson Source Type: research

Management of High-Grade Gliomas in the Elderly
The incidence of glioblastoma (GBM) has been increasing over the past several decades with majority of this increase occurring in patients older than 70 years. In spite of the growing body of evidence in this area, it is still unclear as to the optimal management of elderly patients with GBM. The elderly are a heterogeneous population with a range of comorbid conditions, and functional, cognitive, and physiological changes, and ideally treatment decisions should be made in the context of a comprehensive geriatric assessment. Patients with a poor performance status or assessed as “frail” might be considered for ...
Source: Seminars in Radiation Oncology - September 15, 2014 Category: Cancer & Oncology Authors: Michelle Ferguson, George Rodrigues, Jeffrey Cao, Glenn Bauman Source Type: research

Bevacizumab and Other Targeted Agents in the Upfront Treatment of Glioblastoma
The standard treatment for glioblastoma, the most common primary malignant brain tumor, has been maximal safe surgical resection followed by the combination of radiation and temozolomide. Bevacizumab has shown promise in the treatment of glioblastoma; it and a number of other new, targeted agents have been tested in combination with radiation and temozolomide. Results of recent studies of such agents are discussed. Although many of these agents show promise, none as yet has established a new standard of care for these difficult-to-treat tumors. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - September 15, 2014 Category: Cancer & Oncology Authors: Jennifer L. Clarke Source Type: research

New Considerations in Radiation Treatment Planning for Brain Tumors: Neural Progenitor Cell–Containing Niches
The purpose of this critical review is to explore the controversy regarding the relationship between radiation dose to the neural progenitor cell (NPC) niches and patient outcomes, in terms of both toxicity and tumor control. NPCs in the subventricular zone (SVZ) and hippocampus are paradoxically associated with long-term neurocognitive sequelae of brain irradiation, as well as resistance to therapy and tumor recurrence. The reconciliation of these somewhat opposing functions is challenging. Current literature suggests that radiation and other treatments against the NPC in the hippocampus and the SVZ may influence patient ...
Source: Seminars in Radiation Oncology - September 15, 2014 Category: Cancer & Oncology Authors: Carmen Kut, Kristin Janson Redmond Source Type: research

Standardization and Quality Assurance of Radiation Therapy Volumes for Adults With High-Grade Gliomas
Abstract: Standard treatment for Glioblastoma Multiforme (GBM) consists of a combination of chemotherapy and radiation therapy followed by adjuvant chemotherapy. While the optimal dose of radiation therapy has been established, significant variability in volume of tissue irradiated exists. In this article we review the current guidelines, patterns of care, patterns of failure, imaging advances and toxicity related to radiation therapy volumes in the treatment of GBM. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - September 15, 2014 Category: Cancer & Oncology Authors: Shannon Fogh, Michael Wahl, Mekhail Anwar, Daphne Haas-Kogan, Jennifer L. Clarke, Penny K. Sneed Source Type: research

Advanced Magnetic Resonance Imaging Methods for Planning and Monitoring Radiation Therapy in Patients With High-Grade Glioma
(Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - September 15, 2014 Category: Cancer & Oncology Source Type: research

The Genetic Signatures of Pediatric High-Grade Glioma: No Longer a One-Act Play
Advances in understanding pediatric high-grade glioma (pHGG) genetics have revealed key differences between pHGG and adult HGG and have uncovered unique molecular drivers among subgroups within pHGG. The 3 core adult HGG pathways, the receptor tyrosine kinase-Ras-phosphatidylinositide 3-kinase, p53, and retinoblastoma networks, are also disrupted in pHGG, but they exhibit a different spectrum of effectors targeted by mutation. There are also similarities and differences in the genomic landscape of diffuse intrinsic pontine glioma (DIPG) and pediatric nonbrainstem (pNBS)-HGG. In 2012, histone H3 mutations were identified in...
Source: Seminars in Radiation Oncology - September 15, 2014 Category: Cancer & Oncology Authors: Alexander K. Diaz, Suzanne J. Baker Source Type: research

Genetic Markers in Adult High-Grade Gliomas
Diffuse gliomas are the most common primary central nervous system malignancy in adults and most are high grade. Although current morphologic classification by the World Health Organization provides considerable information, significant variability continues to exist in each diagnostic category. Recent molecular advances define distinct molecular signatures and elucidate gliomagenesis pathways, leading to alternative methods for subclassification beyond morphology alone. In addition, each newly described molecular aberration represents a potential new biomarker with variable diagnostic, prognostic, and predictive value for...
Source: Seminars in Radiation Oncology - September 15, 2014 Category: Cancer & Oncology Authors: Melike Pekmezci, Arie Perry Source Type: research

Preface
In this issue of Seminars in Radiation Oncology, experts provide comprehensive reviews of and insights into relevant issues in imaging advances, molecular characterization, and clinical approaches to adult and pediatric high-grade gliomas. It is a privilege for me to be able to serve as the Guest Editor for this issue in which the contributors are mentees, mentors, colleagues, and outstanding physician scientists. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - September 15, 2014 Category: Cancer & Oncology Authors: Daphne Haas-Kogan Source Type: research

Magnetic Resonance–Guided Adaptive Radiotherapy: A Solution to the Future
Magnetic resonance imaging–guided adaptive radiotherapy would make available the best in anatomical and functional imaging during the course of radiation therapy. The possible methodology of magnetic resonance imaging–guided adapted radiotherapy and possible clinical applications are discussed. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Patrick Kupelian, Jan-Jakob Sonke Source Type: research

Clinical Applications for Diffusion Magnetic Resonance Imaging in Radiotherapy
In this article, we review the clinical applications of diffusion magnetic resonance imaging (MRI) in the radiotherapy treatment of several key clinical sites, including those of the central nervous system, the head and neck, the prostate, and the cervix. Diffusion-weighted MRI (DWI) is an imaging technique that is rapidly gaining widespread acceptance owing to its ease and wide availability. DWI measures the mobility of water within tissue at the cellular level without the need of any exogenous contrast agent. For radiotherapy treatment planning, DWI improves upon conventional imaging techniques, by better characterizatio...
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Christina Tsien, Yue Cao, Thomas Chenevert Source Type: research

Magnetic Resonance Imaging of the Tumor Microenvironment in Radiotherapy: Perfusion, Hypoxia, and Metabolism
The tumor microenvironment is characterized by hypoxia, low pH, and high interstitial fluid pressure. Hypoxic regions in tumors with low partial pressure of oxygen (pO2) levels can result in resistance to radiotherapy, thus causing local failure. Therefore, it would be desirable to noninvasively measure pO2 levels in the tumor before, during, and after treatment to better customize therapy and follow treatment response. Several techniques used in preclinical and clinical studies to obtain the pO2 status of tissue, such as dynamic contrast-enhanced magnetic resonance imaging, blood oxygen level–dependent imaging, and ...
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Masayuki Matsuo, Shingo Matsumoto, James B. Mitchell, Murali C. Krishna, Kevin Camphausen Source Type: research

The Magnetic Resonance Imaging–Linac System
The current image-guided radiotherapy systems are suboptimal in the esophagus, pancreas, kidney, rectum, lymph node, etc. These locations in the body are not easily accessible for fiducials and cannot be visualized sufficiently on cone-beam computed tomographies, making daily patient set-up prone to geometrical uncertainties and hinder dose optimization. Additional interfraction and intrafraction uncertainties for those locations arise from motion with breathing and organ filling. To allow real-time imaging of all patient tumor locations at the actual treatment position a fully integrated 1.5-T, diagnostic quality, magneti...
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Jan J.W. Lagendijk, Bas W. Raaymakers, Marco van Vulpen Source Type: research

The Australian Magnetic Resonance Imaging–Linac Program
The Australian magnetic resonance imaging (MRI)–Linac program is a $16-million government-funded project to advance the science and clinical practice of exquisite real-time anatomical and physiological adaptive cancer therapy. The centerpiece of the program is a specifically designed 1-T open-bore MRI/6-MV linac system that is planned for delivery and completion of installation in 2014. Current scientific endeavors include engineering discovery in MRI component design, quantifying MRI and linac interactions, and developing image guidance and adaptation strategies. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Paul J. Keall, Michael Barton, Stuart Crozier, On behalf of the Australian MRI-Linac Program, including contributors from the Ingham Institute, Illawarra Cancer Care Centre, Liverpool Hospital, Stanford University, Universities of Newcastle, Queensland, S Source Type: research

The Rotating Biplanar Linac–Magnetic Resonance Imaging System
We have successfully built linac–magnetic resonance imaging (MR) systems based on a linac waveguide placed between open MR planes (perpendicular) or through the central opening of one of the planes (parallel) to improve dosimetric properties. It rotates on a gantry to irradiate at any angle. Irradiation during MR imaging and automatic 2-dimensional MR image–based target tracking and automatic beam steering to the moving target have been demonstrated with our systems. The functioning whole-body system (0.6-T MR and 6-MV linac) has been installed in an existing clinical vault without removing the walls or the cei...
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Biagio Gino Fallone Source Type: research

The ViewRay System: Magnetic Resonance–Guided and Controlled Radiotherapy
A description of the first commercially available magnetic resonance imaging (MRI)–guided radiation therapy (RT) system is provided. The system consists of a split 0.35-T MR scanner straddling 3 60Co heads mounted on a ring gantry, each head equipped with independent doubly focused multileaf collimators. The MR and RT systems share a common isocenter, enabling simultaneous and continuous MRI during RT delivery. An on-couch adaptive RT treatment-planning system and integrated MRI-guided RT control system allow for rapid adaptive planning and beam delivery control based on the visualization of soft tissues. Treatment o...
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Sasa Mutic, James F. Dempsey Source Type: research

A Facility for Magnetic Resonance–Guided Radiation Therapy
Magnetic resonance (MR) imaging is routinely employed in the design of radiotherapy (RT) treatment plans for many disease sites. It is evident that tighter integration of MR imaging into the RT process would increase confidence in dose placement and facilitate the integration of new MR imaging information (including anatomical and functional imaging) into the therapy process. To this end, a dedicated MR-guided RT (MRgRT) facility has been created that integrates a state-of-the-art linear accelerator delivery system, high-dose rate brachytherapy afterloader, and superconducting MR scanner to allow MR-based online treatment ...
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: David A. Jaffray, Marco C. Carlone, Michael F. Milosevic, Stephen L. Breen, Teodor Stanescu, Alexandra Rink, Hamideh Alasti, Anna Simeonov, Michael C. Sweitzer, Jeffrey D. Winter Source Type: research

Introduction: Systems for Magnetic Resonance Image Guided Radiation Therapy
As in-room image guidance has become the standard of practice in radiation therapy, the soft-tissue contrast of x-ray-based imaging techniques has become limiting. This has motivated several institutions to work on the integration of in-room magnetic resonance imaging (MRI) and external-beam radiotherapy. Such an approach poses many technical challenges, and a range of solutions have been explored, investigated, and reported. To date, we are aware of 5 groups that are pursuing a system integration of in-room MRI into radiotherapy guidance. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Cynthia Ménard, Uulke van der Heide Source Type: research

Magnetic Resonance Image Guided Brachytherapy
The application of magnetic resonance image (MRI)–guided brachytherapy has demonstrated significant growth during the past 2 decades. Clinical improvements in cervix cancer outcomes have been linked to the application of repeated MRI for identification of residual tumor volumes during radiotherapy. This has changed clinical practice in the direction of individualized dose administration, and resulted in mounting evidence of improved clinical outcome regarding local control, overall survival as well as morbidity. MRI-guided prostate high-dose-rate and low-dose-rate brachytherapies have improved the accuracy of target ...
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Kari Tanderup, Akila N. Viswanathan, Christian Kirisits, Steven J. Frank Source Type: research

Counterpoint: Opportunities and Challenges of a Magnetic Resonance Imaging–Only Radiotherapy Work Flow
Magnetic resonance (MR) imaging plays an important role in modern radiotherapy. The benefits of MR as compared with those of computed tomography for the definition of target volumes is evident for many soft tissue tumor types. It has been suggested that for these patient groups, the computed tomography examination is unnecessary as part of the preparation for radiotherapy. Here, we review the rationale for an MR-only radiotherapy work flow, as well as the technical challenges and solutions connected to it. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Tufve Nyholm, Joakim Jonsson Source Type: research

Point: Principles of Magnetic Resonance Imaging Integration in a Computed Tomography–Based Radiotherapy Workflow
Computed tomography (CT) is the primary imaging modality on which radiation therapy has been based, leading to a CT-based workflow that is well established. CT provides a geometrically accurate patient model on which accurate radiation planning occurs, and it is the basis of the present state-of-the-art image guidance systems, which are well integrated with the treatment unit. Magnetic resonance imaging (MRI) is becoming an increasingly important tool in radiation oncology, as it can provide anatomical and functional information regarding the tumor and normal tissues, which may be complimentary to information from CT alone...
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Kristy K. Brock, Laura A. Dawson Source Type: research

Magnetic Resonance Imaging Acquisition Techniques for Radiotherapy Planning
Magnetic resonance imaging (MRI) has a number of benefits for the planning of radiotherapy (RT), but its uptake into clinical practice has often been restricted to specialist research sites. There is often a lack of detailed MRI knowledge within the RT community and an apprehension of geometric distortions, both of which prevent its best utilization and merit the introduction of a standardized approach and common guidelines. This review sets out to address some of the issues involved in acquiring MRI scans for RT planning in the context of a number of clinical sites of interest and concludes with recommendations for its be...
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Gary P. Liney, Marinus A. Moerland Source Type: research

The Value of Magnetic Resonance Imaging for Radiotherapy Planning
The success of highly conformal radiotherapy techniques in the sparing of normal tissues or in dose escalation, or both, relies heavily on excellent imaging. Because of its superior soft tissue contrast, magnetic resonance imaging is increasingly being used in radiotherapy treatment planning. This review discusses the current clinical evidence to support the pivotal role of magnetic resonance imaging in radiation oncology. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Piet Dirix, Karin Haustermans, Vincent Vandecaveye Source Type: research

Introduction: Magnetic Resonance Imaging Comes of Age in Radiation Oncology
With the invention of spatial encoding of the nuclear magnetic resonance (MR) signal by Lauterbur and Mansfield, MR imaging (MRI) was born. After the first image of in vivo human anatomy in 1977, evolution of the technology accelerated over the ensuing decade, and clinical translation to the field of diagnostic radiology flourished. Because MRI, much like radiation oncology, is at the crossroads between medicine and chemistry, physics, and computer science, groups with strong interdisciplinary relationships and cross-fertilization became scientifically fruitful. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - June 16, 2014 Category: Cancer & Oncology Authors: Cynthia Ménard, Uulke A. van der Heide Source Type: research

Stereotactic Body Radiotherapy in the Treatment of Pancreatic Cancer
Most patients diagnosed with pancreatic cancer are unable to have a curative surgical resection. Chemoradiation is a standard of care treatment for patients with locally advanced unresectable disease, but local failure rates are high with conventionally fractionated radiotherapy. However, stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy offers an alternative type of radiation therapy, which allows for the delivery of high-dose, conformal radiation. The high doses and shorter overall treatment time with SBRT may provide advantages in local control, disease outcomes, quality of life, and cost-effec...
Source: Seminars in Radiation Oncology - March 13, 2014 Category: Cancer & Oncology Authors: Nicholas Trakul, Albert C. Koong, Daniel T. Chang Source Type: research

Utilization of Intensity-Modulated Radiation Therapy and Image-Guided Radiation Therapy in Pancreatic Cancer: Is It Beneficial?
The recent development of intensity-modulated radiation therapy (IMRT) and improvements in image-guided radiotherapy (IGRT) have provided considerable advances in the utilization of radiation therapy (RT) for the management of pancreatic cancer. IGRT allows for the reduction of treatment volumes, potentially less chance of a marginal miss, and quality assurance of gastrointestinal filling, while IMRT has been shown to reduce both sudden and late side effects compared with 3-dimensional conformal RT. Here, we review published data and provide essential recommendations on the utilization of IMRT and IGRT for the management o...
Source: Seminars in Radiation Oncology - March 13, 2014 Category: Cancer & Oncology Authors: Adam S. Reese, Wei Lu, William F. Regine Source Type: research

The Role of Intraoperative Radiation Therapy in Patients With Pancreatic Cancer
Intraoperative radiation therapy (IORT) techniques allow for the delivery of high doses of radiation therapy while excluding part or all of the nearby dose-limiting sensitive structures. Therefore, the effective radiation dose is increased and local tumor control potentially improved. This is pertinent in the case of pancreatic cancer because local failure rates are as high as 50%-80% in patients with resected and locally advanced disease. Available data in patients receiving IORT after pancreaticoduodenectomy reveal an improvement in local control, though overall survival benefit is unclear. Series of patients with locall...
Source: Seminars in Radiation Oncology - March 13, 2014 Category: Cancer & Oncology Authors: Manisha Palta, Christopher Willett, Brian Czito Source Type: research

Neoadjuvant vs Adjuvant Therapy for Resectable Pancreatic Cancer: The Evolving Role of Radiation
A major challenge with pancreatic cancer management is in the discrimination of clearly resectable tumors from those that would likely be accompanied by a positive resection margin if upfront surgery was attempted. The standard of care for clearly resectable pancreatic cancer remains surgery followed by adjuvant therapy, but there is considerable controversy over whether such therapeutic adjuvant strategies should include radiotherapy. Furthermore, in a malignancy with such high rates of distant metastasis, investigators are now exploring the feasibility and outcomes of delivering therapy in the neoadjuvant setting, both f...
Source: Seminars in Radiation Oncology - March 13, 2014 Category: Cancer & Oncology Authors: Sarah Hoffe, Nikhil Rao, Ravi Shridhar Source Type: research

Management of Borderline Resectable Pancreatic Cancer
Borderline resectable pancreatic cancers are those that, although technically resectable, are at high risk for margin-positive resection following surgery de novo. Generally, such cancers are characterized by localized primary tumors that involve the mesenteric vasculature to a limited degree and that may require venous or hepatic arterial resection at pancreatectomy. In this article, we review diagnosis and staging algorithms, pretreatment strategies, and multidisciplinary treatment protocols for patients with this stage of disease. The rationale for and results following treatment with neoadjuvant chemotherapy and chemor...
Source: Seminars in Radiation Oncology - March 13, 2014 Category: Cancer & Oncology Authors: Matthew H.G. Katz, Christopher H. Crane, Gauri Varadhachary Source Type: research

Defining the Role of Adjuvant Therapy: Cholangiocarcinoma and Gall Bladder Cancer
Biliary tract cancers are a rare subgroup of malignancies that include gall bladder carcinoma and cholangiocarcinoma. They generally carry a poor prognosis based on the advanced nature of disease at presentation and overall treatment refractoriness. Surgical resection remains the optimal treatment for long-term survival, with consideration of neoadjuvant or adjuvant therapies. In this review, we summarize the role of adjuvant treatments including radiation therapy, chemotherapy, and concurrent chemoradiation with the existing clinical evidence for each treatment decision. Given the rarity of these tumors, the evidence prov...
Source: Seminars in Radiation Oncology - March 13, 2014 Category: Cancer & Oncology Authors: Terence M. Williams, Lonika Majithia, Samuel J. Wang, Charles R. Thomas Source Type: research

Defining the Role of Adjuvant Therapy: Ampullary and Duodenal Adenocarcinoma
Adenocarcinomas of the ampulla of Vater and duodenum are more rare than pancreatic cancer and have a better prognosis. However, studies conducted on the management of these cancers, such as adjuvant chemotherapy and radiation therapy, are limited by small sample sizes and series that are retrospective. This review evaluates ampullary and duodenal adenocarcinomas with regard to incidence, anatomy, prognostic features, patterns of failure, and the available literature studying adjuvant therapy. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - March 13, 2014 Category: Cancer & Oncology Authors: Salma K. Jabbour, David Mulvihill Source Type: research

Intraductal Papillary Mucinous Neoplasm: Clinical Surveillance and Management Decisions
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively rare cystic neoplasm. Although most IPMNs appear to be benign and may be managed by surveillance, all IPMNs are considered premalignant lesions with malignant potential. As such, current efforts are focused on identifying those neoplasms that are at high risk for malignancy to optimize treatment strategy and outcome. IPMNs with invasive carcinoma have clinical outcomes that approach those of conventional pancreatic ductal adenocarcinoma. Management guidelines recommend surgical resection for IPMNs with high-risk imaging or cytologic features. Th...
Source: Seminars in Radiation Oncology - March 13, 2014 Category: Cancer & Oncology Authors: Joanna Y. Chin, Martha B. Pitman, Theodore S. Hong Source Type: research

The Clinical Utility of Biomarkers in the Management of Pancreatic Adenocarcinoma
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and survival rates have seen minimal improvement over the past few decades. Although results are poor, surgical resection is considered the only curative therapeutic intervention for pancreatic cancer, thereby emphasizing the significance of effective diagnostic and prognostic tools to improve outcomes. As such, biomarkers play a promising role in the development of personalized treatments for patients with pancreatic cancer. Prognostic biomarkers, such as serum carbohydrate antigen 19-9 in particular, as well as cancer stem cell ma...
Source: Seminars in Radiation Oncology - March 13, 2014 Category: Cancer & Oncology Authors: Khalid A. Jazieh, Michael B. Foote, Luis A. Diaz Source Type: research

Pancreaticobiliary Malignancies: Past, Present, and Future
Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less.—Marie Curie This issue of Seminars in Radiation Oncology is dedicated to providing oncologists with an updated review of the roles and controversies surrounding radiation therapy in duodenal, ampullary, gall bladder, bile duct, and pancreatic cancers. Multidisciplinary management of pancreaticobiliary malignancies is needed to decrease treatment-related toxicity and improve quality of life. Paired with innovations in diagnostic imaging, surgical techniques, systemic drug delivery, symptom manag...
Source: Seminars in Radiation Oncology - March 13, 2014 Category: Cancer & Oncology Authors: Joseph M. Herman Source Type: research

Comparative Effectiveness Research in Practice and Policy for Radiation Oncology
Interest in comparative effectiveness research (CER) has increased dramatically over the past decade, yet perceptions about what comprises CER varies. CER has several attributes relevant to practice and policy: (1) The goal of CER is to inform decisions about health care. (2) Literature synthesis is used in addition to primary research. (3) CER evaluates not only overall outcomes for the population but also evaluates subgroups that may have heterogeneous outcomes. (4) Research places an emphasis on outcomes in the “real-world” settings. (5) Outcomes studied should be relevant to patients. In radiation oncology,...
Source: Seminars in Radiation Oncology - December 5, 2013 Category: Cancer & Oncology Authors: William F. Lawrence Source Type: research

Comparative Effectiveness Research: Moving Medical Oncology Forward
Comparative effectiveness research (CER) is critically needed in medical oncology to improve the care being delivered to oncology patients. As medical oncologists are forced to rely on insufficient data as a part of daily treatment decision making, and as the cancer treatment landscape evolves quickly relative to other areas of medicine, CER is particularly pressing in our field. Continued reliance on randomized clinical trials is a part of the solution, but it cannot be the sole answer. As new and richer data sources become available addressing quality of life, resource utilization, and other critical elements, the implem...
Source: Seminars in Radiation Oncology - December 5, 2013 Category: Cancer & Oncology Authors: Bradford R. Hirsch, S. Yousuf Zafar Source Type: research

Comparative Effectiveness Research: Opportunities in Surgical Oncology
Comparative effectiveness research (CER) is especially applicable to surgical oncology because of the numerous challenges associated with conducting surgical randomized controlled trials, and the opportunity to apply various CER methodologies to answer surgical questions. In this article, several past randomized trials or attempted trials are described to demonstrate challenges related to feasibility, patient selection and generalizability, and timeliness trial results to inform clinical practice. Thus, there is a gap between these “efficacy” studies (ie, randomized trials) and “effectiveness” resea...
Source: Seminars in Radiation Oncology - December 5, 2013 Category: Cancer & Oncology Authors: Heather B. Neuman, Caprice C. Greenberg Source Type: research

Comparative Effectiveness Research in Radiation Oncology: Stereotactic Radiosurgery, Hypofractionation, and Brachytherapy
Radiation oncology encompasses a diverse spectrum of treatment modalities, including stereotactic radiosurgery, hypofractionated radiotherapy, and brachytherapy. Though all these modalities generally aim to do the same thing—treat cancer with therapeutic doses of radiation while relatively sparing normal tissue from excessive toxicity, the general radiobiology and physics underlying each modality are distinct enough that their equivalence is not a given. Given the continued innovation in radiation oncology, the comparative effectiveness of these modalities is important to review. Given the broad scope of radiation on...
Source: Seminars in Radiation Oncology - December 5, 2013 Category: Cancer & Oncology Authors: Sanjay Aneja, James B. Yu Source Type: research

Comparative Effectiveness Research in Radiation Oncology: Assessing Technology
This article outlines the elements of effective technology assessment, identifies key challenges to comparative effectiveness studies of new radiation oncology technologies, and reviews several examples of comparative effectiveness studies in radiation oncology, including studies on conformal radiation, IMRT, proton therapy, and other concurrent new technologies. (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - December 5, 2013 Category: Cancer & Oncology Authors: Aileen B. Chen Source Type: research

Decision Analysis and Cost-Effectiveness Analysis for Comparative Effectiveness Research—A Primer
Although the analysis of real-world data is the foundation of comparative effectiveness analysis, not all clinical questions are easily approached with patient-derived information. Decision analysis is a set of modeling and analytic tools that simulate treatment and disease processes, including the incorporation of patient preferences, thus generating optimal treatment strategies for varying patient, disease, and treatment conditions. Although decision analysis is informed by evidence-derived outcomes, its ability to test treatment strategies under different conditions that are realistic but not necessarily reported in the...
Source: Seminars in Radiation Oncology - December 5, 2013 Category: Cancer & Oncology Authors: David J. Sher, Rinaa S. Punglia Source Type: research

An Overview of Methods for Comparative Effectiveness Research
Comparative effectiveness research (CER) is a broad category of outcomes research encompassing many different methods employed by researchers and clinicians from numerous disciplines. The goal of cancer-focused CER is to generate new knowledge to assist cancer stakeholders in making informed decisions that will improve health care and outcomes of both individuals and populations. There are numerous CER methods that may be used to examine specific questions, including randomized controlled trials, observational studies, systematic literature reviews, and decision sciences modeling. Each has its strengths and weaknesses. To ...
Source: Seminars in Radiation Oncology - December 5, 2013 Category: Cancer & Oncology Authors: Anne-Marie Meyer, Stephanie B. Wheeler, Morris Weinberger, Ronald C. Chen, William R. Carpenter Source Type: research

Comparative Effectiveness Research in Oncology: The Promise, Challenges, and Opportunities
In this report, CER was defined as the “generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat and monitor a clinical condition, or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels.” (Source: Seminars in Radiation Oncology)
Source: Seminars in Radiation Oncology - December 5, 2013 Category: Cancer & Oncology Authors: Ronald C. Chen Source Type: research

Understanding the Tumor Microenvironment and Radioresistance by Combining Functional Imaging With Global Gene Expression
The objective of this review is to present an argument for performing joint analyses between functional imaging with global gene expression studies. The reason for making this link is that tumor microenvironmental influences on functional imaging can be uncovered. Such knowledge can lead to (1) more informed decisions regarding how to use functional imaging to guide therapy and (2) discovery of new therapeutic targets. As such, this approach could lead to identification of patients who need aggressive treatment tailored toward the phenotype of their tumor vs those who could be spared treatment that carries risk for more no...
Source: Seminars in Radiation Oncology - September 20, 2013 Category: Cancer & Oncology Authors: Mark W. Dewhirst, Jen-Tsan Chi Source Type: research

Cell Death–Stimulated Cell Proliferation: A Tissue Regeneration Mechanism Usurped by Tumors During Radiotherapy
The death of all the cancer cells in a tumor is the ultimate goal of cancer therapy. Therefore, much of the current effort in cancer research is focused on activating cellular machinery that facilitates cell death such as factors involved in causing apoptosis. However, recently, a number of studies point to some counterintuitive roles for apoptotic caspases in radiation therapy as well as in tissue regeneration. It appears that a major function of apoptotic caspases is to facilitate tissue regeneration and tumor cell repopulation during cancer therapy. Because tumor cell repopulation has been shown to be important for loca...
Source: Seminars in Radiation Oncology - September 20, 2013 Category: Cancer & Oncology Authors: Mary A. Zimmerman, Qian Huang, Fang Li, Xinjiang Liu, Chuan-Yuan Li Source Type: research

Inhibiting Vasculogenesis After Radiation: A New Paradigm to Improve Local Control by Radiotherapy
Tumors are supported by blood vessels, and it has long been debated whether their response to irradiation is affected by radiation damage to the vasculature. We have shown in preclinical models that, indeed, radiation is damaging to the tumor vasculature and strongly inhibits tumor angiogenesis. However, the vasculature can recover by colonization from circulating cells, primarily proangiogenenic CD11b+ monocytes or macrophages from the bone marrow. This secondary pathway of blood vessel formation, known as vasculogenesis, thus acts to restore the tumor vasculature and allows the tumor to recur following radiation. The sti...
Source: Seminars in Radiation Oncology - September 20, 2013 Category: Cancer & Oncology Authors: Brown J. Martin Source Type: research

Radiation as an Immune Modulator
Radiation therapy is currently one of the most widely utilized treatment strategies in the clinical management of cancer. Classically, radiation therapy was developed as an anticancer treatment on the basis of its capacity to induce DNA double strand breaks in exposed cancer cells, ultimately resulting in tumor cell death. Recently, our understanding of radiation effects has expanded widely in terms of the consequences of radiation-induced tumor cell death and the pertinent cells, signaling pathways, and molecular sensors that modify the tumor response to radiation. It is now well accepted that inflammation plays a complex...
Source: Seminars in Radiation Oncology - September 20, 2013 Category: Cancer & Oncology Authors: Byron Burnette, Ralph R. Weichselbaum Source Type: research

Optimization of Tumor Radiotherapy With Modulators of Cell Metabolism: Toward Clinical Applications
Most solid tumors are characterized by unstable perfusion patterns, creating regions of hypoxia that are detrimental to radiotherapy treatment response. Because postsurgical radiotherapy, alone or in combination with other interventions, is a first-line treatment for many malignancies, strategies aimed at homogeneously increasing tumor pO2 have been the focus of intense research over the past decades. Among other approaches of demonstrable clinical and preclinical utility, this review focuses on those directly targeting oxygen consumption to redirect oxygen from a metabolic fate to the stabilization of radiation-induced DN...
Source: Seminars in Radiation Oncology - September 20, 2013 Category: Cancer & Oncology Authors: Pierre Danhier, Christophe J. De Saedeleer, Oussama Karroum, Géraldine De Preter, Paolo E. Porporato, Bénédicte F. Jordan, Bernard Gallez, Pierre Sonveaux Source Type: research

The Roles of Reactive Oxygen Species and Autophagy in Mediating the Tolerance of Tumor Cells to Cycling Hypoxia
Tumor hypoxia (low oxygenation) causes treatment resistance and poor patient outcome. A substantial fraction of tumor cells experience cycling hypoxia, characterized by transient episodes of hypoxia and reoxygenation. These cells are under a unique burden of stress, mediated by excessive production of reactive oxygen species (ROS). Cellular components damaged by ROS can be cleared by autophagy, rendering cycling hypoxic tumor cells particularly vulnerable to inhibition of autophagy and its upstream regulatory pathways. Activation of the PERK-mediated signaling arm of the unfolded protein response during hypoxia plays a cri...
Source: Seminars in Radiation Oncology - September 20, 2013 Category: Cancer & Oncology Authors: Marianne Koritzinsky, Bradly G. Wouters Source Type: research