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Radiation oncology has evolved as a discipline and the physicians who practice radiation oncology are adapting to the changing landscape of oncology management. The skill set for the modern radiation oncologist has matured as the requirements for modern patient care have become increasingly complex both in patient evaluation and treatment execution. Radiation oncology interacts with all medical and surgical subspecialties and advanced radiation therapy treatment plans require nimble use of volumetric anatomic and metabolic image sets and applied pathology to contour targets for successful treatment. Although multidisciplinary care management can serve to confirm and validate a treatment plan among providers, the number of providers involved with an individual patient management plan can also generate confusion and mixed messaging for the patient and their family. Because radiation oncologists work with every discipline and see patients weekly on treatment, often the relationship between the radiation oncologist and the patient can serve as a bridge between disciplines and radiation oncologists can serve to align the disciplines with the patient to re-affirm the care plan, limit confusion, and generate confidence for the patient with the plan and the providers. In this chapter, we will review the changing role of the radiation oncologist as we continually move directly into the mainstream of patient care, in equal partnership to medical oncology with highly advanced tools for modern therapy. Survivorships models of care will mature as radiation oncologists become more integrated into primary and follow up management of each cancer patient.

Technology and computational analytics are moving forward at an extraordinary rate with changes in patient care and department workflows. This rapid pace of change often requires initiating and maintaining the educational support at multiple levels to introduce technology to radiation oncology staff members. Modern physics quality assurance and dosimetry treatment planning now require expertise beyond traditional skill based in computational algorithms and image management including quality assurance of the process of image acquisition and fusion of image datasets. Expertise in volumetric anatomy and normal tissue contouring are skills now performed by physics/dosimetry in collaboration with physicians and these skills are required in modern physics dosimetry training programs. In this chapter, challenges of modern radiation planning are reviewed for each disease site. Skills including future applications of image integration into planning objects and the future utility of artificial intelligence in modern radiation therapy treatment planning are reviewed as these issues will need to be added to modern training programs.

Clinical trials in radiation oncology have improved our translational science and patient care. All patients referred to departments of radiation oncology can be invited to participate in a clinical trial with multiple venues. Study endpoints can include intradepartmental endpoints to improve workflow and patient access as well as interdepartmental clinical translational trials that include the National Clinical Trials Network (NCTN) and industry. The quality of the trial is important to trial outcome and influences interpretation of the results of the study and how the results can be applied to patient care moving forward. Clinical trials in radiation oncology to date have accomplished much, however many important questions remain as patient care matures and systemic therapies become more sophisticated and associated with specific biomarkers and cellular expression products. In this chapter we review the history of clinical trials in radiation oncology and review the current status of the structure of quality assurance in clinical trials. We will review unanswered questions and areas to study in each disease area and how to design strategy for trials to address modern unmet needs in our discipline.

Prostate cancer afflicts a substantial portion of the male population with increasing incidence each decade after the age of 40. Standard of care for localized disease at presentation includes prostatectomy and/or radiation therapy which can include management of pelvic lymph nodes. However, the selection of lymph nodes treated by radiotherapy remains variable among practitioners including individual practitioners in the same institution. We present a patient with prostate adenocarcinoma who underwent radical prostatectomy with adjuvant radiotherapy for lymph node involvement and developed mesorectal failure secondary to metastatic spread to untreated tissue.

Intentional and unintentional radiation exposures have a powerful impact on normal tissue function and can induce both short-term and long-term injury to all cell systems. Radiation effects can last a lifetime for a patient and can produce complications for all organ systems. Primary care and emergency medicine health-care providers should understand acute and late effects of radiation treatment and exposure and how these interrelate with patient acute health care. Access to patients’ entire medical record portfolios as well as communication strategies with radiation experts needs to be available. The management of radiation’s acute and late effects in adults and pediatrics is presented.

Proton therapy is increasing in utilization worldwide at a rapid rate. With process improvements in costs, footprints, and continued advances in the delivery of care, including intensity modulation and image guidance, proton therapy may evolve into standard treatment with photon radiation therapy. This chapter reviews process improvements in proton therapy and the application in modern care.

Oncology clinical trials provide opportunity to advance care for patients with cancer. Bridging basic science with bedside care, cancer clinical trials have brought new and updated scientific knowledge at a rapid pace. Managing subject data in translation science requires a sophisticated informatics infrastructure that will enable harmonized datasets across all areas that could influence outcomes. Successful translational science requires that all relevant information be made readily available in a digital format that can be queried in a facile manner. Through a translational science prism, we look at past issues in cancer clinical trials and the new National Institutes of Health/National Cancer Institute initiative to address the need of database availability at an enterprise level.

Radiation therapy delivered post-prostatectomy can provide durable disease-free clinical outcomes. There remains debate as to whether the radiation should be applied to patients with high risk features post-surgery or deferred until there is biomarker evidence of clinical recurrence. Prior to the development of advanced-technology metabolic and anatomic imaging, the radiation therapy treatment fields were applied based on historical models of patterns of failure including the former capsule region, undersurface of the bladder, and the bladder urethral anastomosis. Although outcomes of therapy were good, the choice of the target was not image directed. Modern imaging has provided an advantage for targeting as radiation oncologists can be more secure of high-risk areas and in turn titrate dose to regions deemed of intermediate and low risk. In this paper we describe strategies for application of modern axumin imaging for patient care with radiation therapy post prostatectomy.

As treatment for prostate cancer matures with many options for local, regional and systemic care, patients are living longer. Coupled with aggressive therapy for oligometastatic disease and improvements in multiple treatment pathways including radiopharmacy, both disease-free and overall survival are improving for many patients. Success can also bring new challenges that require new thought processes for care. In this paper we present two patients who had undergone previous radiation therapy for adenocarcinoma of the prostate with curative intent who required consideration for re-irradiation each more than 15 years away from primary management.

The discovery of radiation has led to many advances. Guidelines have been created to minimize radiation exposure and treatment management following both unintentional and intentional exposure. The effects of radiation exposure on specific tissues varies. Tragic consequences can result, ranging from severe, acute injury to long- lasting effects that present years after the initial exposure. In this chapter we provide observations that demonstrate the importance of understanding guidelines to minimize radioactive exposure and the expectations and treatment management following exposure. For the safety and well-being of patients, health care professionals need to remain well-informed to minimize the risks of this tool.

The Children's Oncology Group (COG) has a strong quality assurance (QA) program managed by the Imaging and Radiation Oncology Core (IROC). This program consists of credentialing centers and providing real-time management of each case for protocol compliant target definition and radiation delivery. In the International Society of Pediatric Oncology (SIOP), the lack of an available, reliable online data platform has been a challenge and the European Society for Paediatric Oncology (SIOPE) quality and excellence in radiotherapy and imaging for children and adolescents with cancer across Europe in clinical trials (QUARTET) program currently provides QA review for prospective clinical trials. The COG and SIOP are fully committed to a QA program that ensures uniform execution of protocol treatments and provides validity of the clinical data used for analysis.

Imaging is essential in successfully executing radiation therapy (RT) in oncology clinical trials. As technically sophisticated diagnostic imaging and RT were incorporated into trials, quality assurance in the National Clinical Trials Network groups entered a new era promoting image acquisition and review. Most trials involving RT require pre- and post-therapy imaging for target validation and outcome assessment. The increasing real-time (before and during therapy) imaging and RT object reviews are to ensure compliance with trial objectives. Objects easily transmit digitally for review from anywhere in the world. Physician interpretation of imaging and image application to RT treatment plans is essential for optimal trial execution. Imaging and RT data sets are used to credential RT sites to confirm investigator and institutional ability to meet trial target volume delineation and delivery requirements. Real-time imaging and RT object reviews can be performed multiple times during a trial to assess response to therapy and application of RT objects. This process has matured into an effective data management mechanism. When necessary, site and study investigators review objects together through web media technologies to ensure the patient is enrolled on the appropriate trial and the intended RT is planned and executed in a trial-compliant manner. Real-time imaging review makes sure: (1) the patient is entered and eligible for the trial, (2) the patient meets trial-specific adaptive therapy requirements, if applicable, and (3) the intended RT is according to trial guidelines. This review ensures the study population is uniform and the results are believable and can be applied to clinical practice.

Intentional and unintentional radiation exposures have a powerful impact on normal tissue function and can induce short-term and long-term injury to all cell systems. Radiation effects can lead to lifetime-defining health issues for a patient and can produce complications to all organ systems. Providers need to understand acute and late effects of radiation treatment and how the fingerprints of therapy can have an impact on health care in later life. This article reviews current knowledge concerning normal tissue tolerance with therapy.

With continued progress and success in clinical care, the management of patients with Hodgkin lymphoma (HL) has undergone continuous revision to improve patient care outcomes and limit acute and late treatment effects on normal tissue imposed by therapy. Hodgkin lymphoma is a disease that affects children, adolescents, and adults. Clinical management strategies are influenced by the patient’s age at diagnosis, tumor burden, response to induction therapy, and potential expectation of treatment impact on normal tissue. The approach to patient management varies in many parts of the world and is influenced by treatment availability, physician training, and medical culture. Differences in approach are important to understand for accurately comparing and contrasting outcome studies. In this article, we will identify current areas of common ground and points of separation in patient care management for HL. Opportunities for clinical trial strategies will be defined for future clinical trials.

Quality assurance (QA) in complex head and neck cancer trials is essential. The need for QA is made more relevant with trials comprised of multiple end points, worldwide participation, and increasing use of adaptive strategies/advanced technology to validate/verify outcome analyses. Integration is necessary for tissue analysis, biomarker assessment, imaging, radiation therapy, chemotherapy, and/or targeted therapy for patients with new diagnosis, relapse, and second head and neck malignancies.

Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy quality assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials.

Integrating tissue analysis and imaging strategies in clinical trial objectives is an important area of clinical translational research. Clinical trial designs that incorporate clear guidelines for clinical trial execution, definitions of data submission pathways and study deviations, and integration of real time and adaptive quality assurance will provide uniformity of study populations for clinical trial analysis. Essential to clinical trials management is a robust, validated informatics platform to display data and imaging in a uniform manner acquired from diverse platforms and re-presented for both on site and distributed review in a uniform file format. The Quality Assurance Review Center (QARC) uses a robust informatics platform to provide protocol development, site credentialing, data acquisition, case management, capable of both real time and retrospective review of objects, data transfer to clinical trial sponsor and/or industry partner and data archiving. As a member of the Virtual Imaging Evaluation Workspace (VIEW) and the Advanced Technology Quality Assurance (QA) Consortium (ATC), QARC collaborates in the development, sharing and implementation of credentialing tools, digital acquisition and review tools and processes, a common platform for data storage for radiotherapy and imaging with emphasis on compliance to caBIG and 21 CFR Part 11. Recent evidence demonstrates that compliance to study guidelines may have significant influence on study and patient outcome. Head and neck cancer is a very good area to study biopharmacology of treatment response and the quality assurance process is a vehicle for adaptive clinical trial and patient management.

Clinical trials and oncology data management have undergone considerable change in the past decade. Imaging has become a key tool for clinical trials management and a biomarker for clinical trial validation as imaging technologies improve and become more precise. Images have become extremely helpful in determining staging/eligibility, treatment response, and outcome determination including disease recurrence and progression. In modern protocols, images are often reviewed in real time to validate these points in order to improve compliance to study requirements and create uniform patient populations for clinical trials analysis. Data acquisition and management systems are currently in use to acquire and display images in electronic digital formats for view by both on site and off site radiology reviewers. As clinical trials become more global in focus, the ability for databases to accommodate diverse imaging acquisition strategies will become increasingly important for information review.

Radiation therapy has been integral to cancer patient care. The skin is an intentional and unintentional target of therapy, and is sensitive to the volume of normal tissue in the radiation therapy treatment field, daily treatment dose (fractionation), and total treatment dose. We must understand the relationship of these factors to patient outcome as we move toward hypofractionation treatment strategies (radiosurgery). Chemotherapy agents and prescription medications may influence therapy-associated sequelae. Understanding this may prevent significant injury and discomfort. This article reviews established platforms of radiation therapy and sequelae associated with skin therapy. Interactions with other agents and possible predisposition to sequelae are reviewed. Skin cancer resulting from treatment and disease processes associated with possible limited outcome are also reviewed.

Future physicians will likely encounter patients with cancer or cancer survivors.Therefore the acquisition of core competencies in oncology is essential.1–3 We share our experience with the development and implementation of an oncology component in the recently redesigned Learner Centered Integrated Curriculum (LInC) at the University of Massachusetts Medical School. This pre-clinical course content is presented in a cross-disciplinary and longitudinal format that fosters problem solving, communication, lifelong learning skills, and professionalism throughout the undergraduate years and beyond.

Drs. Bekelman and Yahalom’s (1) paper describing radiation therapy (RT) quality assurance (QA) in lymphoma clinical trials places emphasis for RT standards. Insuring study defined dose/volume constraint compliance, RTQA requires central pre-treatment diagnostic imaging and RT plan review. This letter describes Children’s Oncology Group (COG) historical and current RTQA process for Hodgkin’s lymphoma (HL) trials. For 33 years the Quality Assurance Review Center (QARC) has performed RTQA on cooperative group trials. Process improvements demonstrate maturing of clinical trials QA in response to protocol needs. The increasingly crucial role of imaging in clinical trials QA is validated. Pediatric Oncology Group (POG) protocol 8725 (intermediate/advanced staged HL) required 8 chemotherapy cycles +/− Involved Field RT. Initial publication(2) demonstrated no advantage for RT. Retrospective data review revealed 10% survival advantage for patients receiving compliant RT.(3) 30% of patients had treatment deviations including omission of RT to involved sites. To improve compliance, POG required pre-treatment RT review for next generation advanced/early stage HL studies, P9425/P9426(4,5). Strategy improved RT compliance. P9426 required post chemotherapy imaging response treatment adaptation. Retrospective response-imaging central review established that ~50% of patients had discordance between local and central review.(6) COG AHOD0031 (intermediate risk HL) included patient response-adapted therapy. QARC initiated real time response review with integrated imaging (anatomic and metabolic) and RT review prior to RT start. Discordant local and central interpretations were resolved in real time. (7,8) 1733 patients from 251 centers worldwide were enrolled. Near uniform data submission compliance has been obtained with >95% RT compliance in ~600 cases reviewed. Process feasibility allows extension of adaptive treatments based on centrally-confirmed response for the next high risk HL study. QARC-developed an informatics platform and processes that contribute to success of these clinical trials improvements. QARC acquires and manages imaging and RT data in several digital formats(9). The QARC database houses images and RT objects in side-by-side format, enabling remote investigator access. In collaborating with Dr. Purdy and the Advanced Technology Consortium, full digital RT files are received at QARC for review and DVH analysis. Currently strategies to incorporate Dicom compatible pathology objects into the database and use of open-source format for data sharing are being evaluated. The objectives identified in this paper for developing consensus standards and peer-review are in place for cooperative groups. Applying these established programs at enterprise level insures the objectives of this publication are met.

205 Background: Central review is an important trial management and validation tool. Multisite trials require data systems to accommodate diverse image acquisition and review. Breast cancer is challenging as its imaging objects are not always easily shared across departments. Quality Assurance Review Center (QARC) has a diverse portfolio of facile data acquisition and powerful informatics support that meets these needs. We report on the role of QARC in three of the current breast cancer trials from the American College of Surgeons Oncology Group. Methods: QARC data management system includes secure network infrastructure and a validated relational operating database (MAX). QARC has data acquisition/imaging re-distribution expertise for real time response reviews, response measuring tools and corresponding data archive for secondary reviews. MAX includes query ability; records link to digital information. QARC underwent systematic information systems validation process for 21 CFR Part 11. DICOM/non-DICOM files are stored in the QARC PACS. On-site/remote reviewers use MAX to retrieve, view, annotate and save images. Data extracted is securely sent to partner statistical centers. Results: In Z1031, a neoadjuvant endocrine therapy trial, all of the mammographic exams are archived at QARC. For Z1071, a sentinel lymph node trial, pre- and post-treatment ultrasound (US) images of 321 patients were remotely reviewed. For Z1072, the cryoablation US, pre and post-cryoablation MRI for 40 of 47 cases were remotely archived, retrieved and transferred to investigator workstation for post-processing and review. The other 7 patients did not have evaluable imaging studies. In all three trials, the costs of shipping hardcopies of exams and travel to QARC for central review functions were eliminated. Conclusions: QARC data management systems provide diverse informatics supports for multi-institutional trials, ranging from archives of images, provide remote access and download of data, and central review. The vibrant informatics supports meet the growing needs of clinical trials. Future directions include radiation field review for breast cancer trials and the incorporation of pathology microarray analysis as DICOM objects.