A Multidisciplinary Consensus Recommendation on a Synoptic Radiation Treatment Summary: A Commission on Cancer Workgroup Report.

PURPOSE: The radiation treatment summary provides a clinical and technical overview of a patient's full course of radiation therapy. Despite its importance to multiple stakeholders, there is no widely followed radiation treatment summary template. METHODS AND MATERIALS: The Commission on Cancer convened a multistakeholder workgroup to develop a synoptic radiation treatment summary template. The workgroup included individuals with expertise in radiation, medical and surgical oncology, medical physics, oncology informatics, cancer registry, electronic medical record systems, treatment planning systems, and registry information systems. The workgroup iterated a template until consensus was achieved. RESULTS: The consensus radiation treatment summary template is divided into 3 sections that allows for a mix of structured and free text. The first section, "Radiation Course Summary," is meant to provide information that is of broad interest and in a manner that is potentially accessible to patients, their families, and nononcology-trained care team members. The second section, "Anatomic Target Summary," provides information that is potentially useful to oncology-trained care team members who will be primarily interested in which anatomies were irradiated, by what modality, and to what cumulative dose. The third section, "Delivered Prescriptions," summarizes technical information that is primarily of interest and accessible to radiation oncology-trained clinicians, registrars, and researchers. CONCLUSIONS: We have proposed a consensus template with 3 sections to meet the needs of a diverse set of consumers. We recommend that providers, professional societies, and accreditation bodies with interest in the radiation treatment summary continue collaborative efforts to test, iterate, and drive adoption of a synoptic template.

Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline.

INTRODUCTION: The purpose of this guideline is to offer recommendations on fractionation for whole breast irradiation (WBI) with or without a tumor bed boost and guidance on treatment planning and delivery. METHODS AND MATERIALS: The American Society for Radiation Oncology (ASTRO) convened a task force to address 5 key questions focused on dose-fractionation for WBI, indications and dose-fractionation for tumor bed boost, and treatment planning techniques for WBI and tumor bed boost. Guideline recommendations were based on a systematic literature review and created using a predefined consensus-building methodology supported by ASTRO-approved tools for grading evidence quality and recommendation strength. RESULTS: For women with invasive breast cancer receiving WBI with or without inclusion of the low axilla, the preferred dose-fractionation scheme is hypofractionated WBI to a dose of 4000 cGy in 15 fractions or 4250 cGy in 16 fractions. The guideline discusses factors that might or should affect fractionation decisions. Use of boost should be based on shared decision-making that considers patient, tumor, and treatment factors, and the task force delineates specific subgroups in which it recommends or suggests use or omission of boost, along with dose recommendations. When planning, the volume of breast tissue receiving >105% of the prescription dose should be minimized and the tumor bed contoured with a goal of coverage with at least 95% of the prescription dose. Dose to the heart, contralateral breast, lung, and other normal tissues should be minimized. CONCLUSIONS: WBI represents a significant portion of radiation oncology practice, and these recommendations are intended to offer the groundwork for defining evidence-based practice for this common and important modality. This guideline also seeks to promote appropriately individualized, shared decision-making regarding WBI between physicians and patients.

Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence-Based Guideline.

PURPOSE: The purpose is to provide an update the Bone Metastases Guideline published in 2011 based on evidence complemented by expert opinion. The update will discuss new high-quality literature for the 8 key questions from the original guideline and implications for practice. METHODS AND MATERIALS: A systematic PubMed search from the last date included in the original Guideline yielded 414 relevant articles. Ultimately, 20 randomized controlled trials, 32 prospective nonrandomized studies, and 4 meta-analyses/pooled analyses were selected and abstracted into evidence tables. The authors synthesized the evidence and reached consensus on the included recommendations. RESULTS: Available literature continues to support pain relief equivalency between single and multiple fraction regimens for bone metastases. High-quality data confirm single fraction radiation therapy may be delivered to spine lesions with acceptable late toxicity. One prospective, randomized trial confirms both peripheral and spine-based painful metastases can be successfully and safely palliated with retreatment for recurrence pain with adherence to published dosing constraints. Advanced radiation therapy techniques such as stereotactic body radiation therapy lack high-quality data, leading the panel to favor its use on a clinical trial or when results will be collected in a registry. The panel's conclusion remains that surgery, radionuclides, bisphosphonates, and kyphoplasty/vertebroplasty do not obviate the need for external beam radiation therapy. CONCLUSION: Updated data analysis confirms that radiation therapy provides excellent palliation for painful bone metastases and that retreatment is safe and effective. Although adherence to evidence-based medicine is critical, thorough expert radiation oncology physician judgment and discretion regarding number of fractions and advanced techniques are also essential to optimize outcomes when considering the patient's overall health, life expectancy, comorbidities, tumor biology, anatomy, previous treatment including prior radiation at or near current site of treatment, tumor and normal tissue response history to local and systemic therapies, and other factors related to the patient, tumor characteristics, or treatment.

International survey of the treatment of metastatic spinal cord compression.

BACKGROUND AND PURPOSE: Treatment of metastatic spinal cord compression (MSCC) varies significantly. It is useful to understand how radiation oncologists worldwide deal with these challenging and urgent cases. Therefore, a survey of practice patterns of metastatic spinal cord compression was performed among the members of the major radiation oncology organizations in the world to help improve clinical practice. MATERIAL AND METHODS: The survey questions addressed common clinical issues related to the diagnosis and treatment of spinal cord compression in the context of the available data. The survey of practice pattern in the management of MSCC was performed in 2010. There were a total of 269 survey respondents, and 90% of respondents were from hospital-based practice. Statistical analyses were performed at ASTRO headquarter using Microsoft Excel and SPSS. RESULTS: The practice pattern of initial diagnostic and clinical evaluation of patients for MSCC was fairly uniform across the continents and countries. Treatment decision was largely based on patient's general condition, overall oncologic status, and concomitant systemic chemotherapy in this survey. EBRT dose and fractionation patterns were determined by considering the estimated survival time, neurological status such as ambulatory status, previous radiation, and radiation treatment volume. Despite of using similar factors in making treatment decision, there was a significant difference in selecting the radiation dose and fractionation scheme. Selection of re-treatment radiation dose also varied and generally below the published tolerance dose. CONCLUSIONS: Selection of radiation dose and fractionation varied significantly among different continents and countries, while using similar factors to make treatment decision.

Choosing wisely: the American Society for Radiation Oncology's top 5 list.

PURPOSE: To highlight 5 interventions that patients should question, as part of the Choosing Wisely campaign. This initiative, led by the American Board of Internal Medicine Foundation, fosters conversations between physicians and patients about treatments and tests that may be overused, unnecessary, or potentially harmful. METHODS AND MATERIALS: Potential items were initially compiled using an online survey. They were then evaluated and refined by a work group representing the American Society for Radiation Oncology (ASTRO) Clinical Affairs and Quality, Health Policy, and Government Relations Councils. Literature reviews were carried out to support the recommendation and narrative, as well as to provide references for each item. A final list of 5 items was then selected by the ASTRO Board of Directors. RESULTS: ASTRO's 5 recommendations for the Choosing Wisely campaign are the following: (1) Don't initiate whole-breast radiation therapy as a part of breast conservation therapy in women age ≥50 with early-stage invasive breast cancer without considering shorter treatment schedules; (2) don't initiate management of low-risk prostate cancer without discussing active surveillance; (3) don't routinely use extended fractionation schemes (>10 fractions) for palliation of bone metastases; (4) don't routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry; and (5) don't routinely use intensity modulated radiation therapy to deliver whole-breast radiation therapy as part of breast conservation therapy. CONCLUSIONS: The ASTRO list for the Choosing Wisely campaign highlights radiation oncology interventions that should be discussed between physicians and patients before treatment is initiated. These 5 items provide opportunities to offer higher quality and less costly care.

Adjuvant and salvage radiation therapy after prostatectomy: American Society for Radiation Oncology/American Urological Association guidelines.

PURPOSE: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. METHODS AND MATERIALS: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. RESULTS: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. CONCLUSIONS: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review.

Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline.

PURPOSE: The purpose of this guideline is to provide a clinical framework for the use of radiotherapy after radical prostatectomy as adjuvant or salvage therapy. MATERIALS AND METHODS: A systematic literature review using the PubMed®, Embase, and Cochrane databases was conducted to identify peer-reviewed publications relevant to the use of radiotherapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. RESULTS: Guideline statements are provided for patient counseling, the use of radiotherapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a re-staging evaluation. CONCLUSIONS: Physicians should offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy (i.e., seminal vesicle invasion, positive surgical margins, extraprostatic extension) and should offer salvage radiotherapy to patients with prostatic specific antigen or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiotherapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiotherapy as well as the potential benefits of preventing recurrence. The decision to administer radiotherapy should be made by the patient and the multi-disciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. Please visit the ASTRO and AUA websites (http://www.redjournal.org/webfiles/images/journals/rob/RAP%20Guideline.pdf and http://www.auanet.org/education/guidelines/radiation-after-prostatectomy.cfm) to view this guideline in its entirety, including the full literature review.

An international survey on liver metastases radiotherapy.

BACKGROUND: An international survey of radiation therapy (RT) of liver metastases was undertaken by the Liver Cancer Workgroup of the Third International Consensus on Metastases Workshop at the 2010 American Society for Radiation Oncology (ASTRO) meeting. MATERIAL AND METHODS: Canadian, European, Australian, New Zealand and American centers participated in this online survey. The survey had four objectives: 1) to describe the practice patterns for RT of liver metastases; 2) to report on the use of low-dose RT for symptomatic liver metastases; 3) to report on the use of technology; and 4) to describe the regional differences in the management of liver metastases. RESULTS: A total of 69 individuals treating liver metastases with radiotherapy responded to the survey. Regional response rates ranged from 39% to 50%. The primary professional affiliation of all respondents was evenly distributed amongst ASTRO, CARO, ESTRO and TROG/RANZCR. A 36% increase in the average annual number of referrals over the past five years is reported. The majority of referrals were for radical RT. The most common technologies used were 4D-CT (61%), SBRT (55%), IGRT (50%), and/or IMRT (28%). A uniform treatment approach was not found. The most commonly employed radical regimens were 45 Gy in 3 fractions, 40-50 Gy in 5 fractions, and 45 Gy in 15 fractions. Palliative regimens included 20 Gy in 5 fractions, 30 Gy in 10 fractions, 8 Gy in 1 fraction, and 10 Gy in 2 fractions. CONCLUSIONS: This survey suggests radiation oncologists will be seeing more referrals for liver RT. The majority of experience in liver metastases RT is with radical SBRT for focal metastases rather than low-dose palliative RT for symptom control. There is significant variation in technology utilization and dose regimens. Prospective studies or registries may allow for comparison of regimens and identification of parameters to optimize patient selection.

International practice survey on palliative lung radiotherapy: third international consensus workshop on palliative radiotherapy and symptom control.

BACKGROUND: The purpose of this work was to disseminate international practice survey results created in conjunction with the Third International Lung Cancer Consensus Workshop. PATIENTS AND METHODS: In conjunction with the American Society for Radiation Oncology (ASTRO) Guideline for Palliative Lung Cancer Care and International Workshop Consensus statements, an online international practice survey was conducted during the summer of 2010. The survey included demographic, educational, and clinical questions as well as 5 cases exploring the role of external beam radiotherapy, endobronchial brachytherapy, and concurrent chemoradiation. RESULTS: A total of 279 individuals responded to the survey over a 3-month period. Most respondents were hospital-based, academic, or government-funded radiation oncologists. Factors that consistently related to use and choice of external beam dose fractionation included estimated treatment benefit to patient, performance status (PS), symptom severity, patient choice, estimated prognosis, and previous radiation to the same site. Factors consistently not related to use and dose fractionation included requirement for future radiation therapy, department policy, and waiting lists. A significant range of dose fractionation schedules existed for external beam (n = 35) and endobronchial brachytherapy treatment (n = 10). The integration of concurrent chemotherapy was recorded by a significant minority of respondents despite lack of level I evidence to support its use. Geographic differences in the use of external beam dose fractionation and of concurrent chemotherapy were seen. CONCLUSIONS: Various patient, tumor, treatment, and logistic factors are associated with the variable use and external beam dose fractionation of palliative lung treatments. The copublication of the ASTRO Guideline for Palliative Lung Cancer Care and International Workshop Consensus statements should assist clinicians by providing evidence-based care.

Consensus statement on palliative lung radiotherapy: third international consensus workshop on palliative radiotherapy and symptom control.

The purpose of this work is to disseminate a consensus statement on palliative radiotherapy (RT) of lung cancer created in conjunction with the Third International Lung Cancer Consensus Workshop. The palliative lung RT workshop committee agreed on 5 questions relating to (1) patient selection, (2) thoracic external-beam radiation therapy (XRT) fractionation, (3) endobronchial brachytherapy (EBB), (4) concurrent chemotherapy (CC), and (5) palliative endpoint definitions. A PubMed search for primary/cross-referenced practice guidelines, consensus statements, meta-analyses, and/or systematic reviews was conducted. Final consensus statements were created after review and discussion of the available evidence. The following summary statements reflect the consensus of the international working group. 1. Key factors involved in the decision to deliver palliative RT include performance status, tumor stage, pulmonary function, XRT volume, symptomatology, weight loss, and patient preference. 2. Palliative thoracic XRT is generally indicated for patients with stage IV disease with current/impending symptoms and for patients with stage III disease treated for palliative intent. 3. There is no evidence to routinely recommend EBB alone or in conjunction with other palliative maneuvers in the initial palliative management of endobronchial obstruction resulting from lung cancer. 4. There is currently no evidence to routinely recommend CC with palliative-intent RT. 5. Standard assessment of symptoms and health-related quality of life (QOL) using validated questionnaires should be carried out in palliative RT lung cancer trials. Despite an expanding literature, continued prospective randomized investigations to better define the role of XRT, EBB, and CC in the context of thoracic palliation of patients with lung cancer is needed.

Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases.

PURPOSE: To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the 2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time. METHODS AND MATERIALS: A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey. RESULTS: Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments. CONCLUSION: An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline.

PURPOSE: To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. METHODS AND MATERIALS: Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. RESULTS: The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. CONCLUSIONS: Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).

Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline.

PURPOSE: To present guidance for patients and physicians regarding the use of radiotherapy in the treatment of bone metastases according to current published evidence and complemented by expert opinion. METHODS AND MATERIALS: A systematic search of the National Library of Medicine's PubMed database between 1998 and 2009 yielded 4,287 candidate original research articles potentially applicable to radiotherapy for bone metastases. A Task Force composed of all authors synthesized the published evidence and reached a consensus regarding the recommendations contained herein. RESULTS: The Task Force concluded that external beam radiotherapy continues to be the mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases. Various fractionation schedules can provide significant palliation of symptoms and/or prevent the morbidity of bone metastases. The evidence for the safety and efficacy of repeat treatment to previously irradiated areas of peripheral bone metastases for pain was derived from both prospective studies and retrospective data, and it can be safe and effective. The use of stereotactic body radiotherapy holds theoretical promise in the treatment of new or recurrent spine lesions, although the Task Force recommended that its use be limited to highly selected patients and preferably within a prospective trial. Surgical decompression and postoperative radiotherapy is recommended for spinal cord compression or spinal instability in highly selected patients with sufficient performance status and life expectancy. The use of bisphosphonates, radionuclides, vertebroplasty, and kyphoplasty for the treatment or prevention of cancer-related symptoms does not obviate the need for external beam radiotherapy in appropriate patients. CONCLUSIONS: Radiotherapy is a successful and time efficient method by which to palliate pain and/or prevent the morbidity of bone metastases. This Guideline reviews the available data to define its proper use and provide consensus views concerning contemporary controversies or unanswered questions that warrant prospective trial evaluation.

Palliative thoracic radiotherapy in lung cancer: An American Society for Radiation Oncology evidence-based clinical practice guideline.

PURPOSE: To provide guidance to physicians and patients with regard to the use of external beam radiotherapy, endobronchial brachytherapy, and concurrent chemotherapy in the setting of palliative thoracic treatment for lung cancer, based on available evidence complemented by expert opinion. METHODS AND MATERIALS: A Task Force authorized by the American Society for Radiation Oncology (ASTRO) Board of Directors synthesized and assessed evidence from 3 systematic reviews on the following topics: (1) dose fractionation in thoracic external beam radiotherapy (EBRT); (2) clinical utility of initial and salvage endobronchial brachytherapy (EBB); and (3) use of concurrent chemotherapy (CC) with palliative thoracic radiotherapy. Practice guideline recommendations were produced and are contained herein. RESULTS: Studies suggest that higher dose/fractionation palliative EBRT regimens (eg, 30 Gy/10 fraction equivalent or greater) are associated with modest improvements in survival and total symptom score, particularly in patients with good performance status. As these improvements are associated with an increase in esophageal toxicity, various shorter EBRT dose/fractionation schedules (eg, 20 Gy in 5 fractions, 17 Gy in 2 weekly fractions, 10 Gy in 1 fraction), which provide good symptomatic relief with fewer side effects, can be used for patients requesting a shorter treatment course and/or in those with a poor performance status. No defined role for EBB in the routine initial palliative treatment of chest disease has been demonstrated; however, EBB can be a reasonable option for the palliation of endobronchial lesions causing obstructive symptomatology including lung collapse, or for hemoptysis after EBRT failure. The integration of concurrent chemotherapy with palliative intent/fractionated radiotherapy is not currently supported by the medical literature. CONCLUSION: This Guideline is intended to serve as a guide for the use of EBRT, EBB, and CC in thoracic palliation of lung cancer outside the clinical trial setting. Further prospective clinical investigations with relevant palliative endpoints into the respective roles of EBB and CC/targeted therapy in the thoracic palliation of lung cancer are warranted, given the current state of the medical literature in these areas.

Fractionation for whole breast irradiation: an American Society for Radiation Oncology (ASTRO) evidence-based guideline.

PURPOSE: In patients with early-stage breast cancer treated with breast-conserving surgery, randomized trials have found little difference in local control and survival outcomes between patients treated with conventionally fractionated (CF-) whole breast irradiation (WBI) and those receiving hypofractionated (HF)-WBI. However, it remains controversial whether these results apply to all subgroups of patients. We therefore developed an evidence-based guideline to provide direction for clinical practice. METHODS AND MATERIALS: A task force authorized by the American Society for Radiation Oncology weighed evidence from a systematic literature review and produced the recommendations contained herein. RESULTS: The majority of patients in randomized trials were aged 50 years or older, had disease Stage pT1-2 pN0, did not receive chemotherapy, and were treated with a radiation dose homogeneity within ±7% in the central axis plane. Such patients experienced equivalent outcomes with either HF-WBI or CF-WBI. Patients not meeting these criteria were relatively underrepresented, and few of the trials reported subgroup analyses. For patients not receiving a radiation boost, the task force favored a dose schedule of 42.5 Gy in 16 fractions when HF-WBI is planned. The task force also recommended that the heart should be excluded from the primary treatment fields (when HF-WBI is used) due to lingering uncertainty regarding late effects of HF-WBI on cardiac function. The task force could not agree on the appropriateness of a tumor bed boost in patients treated with HF-WBI. CONCLUSION: Data were sufficient to support the use of HF-WBI for patients with early-stage breast cancer who met all the aforementioned criteria. For other patients, the task force could not reach agreement either for or against the use of HF-WBI, which nevertheless should not be interpreted as a contraindication to its use.

Imaging for assessment of radiation-induced normal tissue effects.

Imaging can provide quantitative assessment of radiation-induced normal tissue effects. Identifying an early sign of normal tissue damage with imaging would have the potential to predict organ dysfunction, thereby allowing reoptimization of treatment strategies based on individual patients' risks and benefits. Early detection with noninvasive imaging may enable interventions to mitigate therapy-associated injury before its clinical manifestation. Furthermore, successive imaging may provide an objective assessment of the impact of such mitigation therapies. However, many problems make application of imaging to normal tissue assessment challenging, and further work is required to establish imaging biomarkers as surrogate endpoints of clinical outcome. The performance of clinical trials in which normal tissue injury is a clearly defined endpoint would greatly aid in realization of these goals.

Radiation dose-volume effects in the brain.

We have reviewed the published data regarding radiotherapy (RT)-induced brain injury. Radiation necrosis appears a median of 1-2 years after RT; however, cognitive decline develops over many years. The incidence and severity is dose and volume dependent and can also be increased by chemotherapy, age, diabetes, and spatial factors. For fractionated RT with a fraction size of <2.5 Gy, an incidence of radiation necrosis of 5% and 10% is predicted to occur at a biologically effective dose of 120 Gy (range, 100-140) and 150 Gy (range, 140-170), respectively. For twice-daily fractionation, a steep increase in toxicity appears to occur when the biologically effective dose is >80 Gy. For large fraction sizes (>or=2.5 Gy), the incidence and severity of toxicity is unpredictable. For single fraction radiosurgery, a clear correlation has been demonstrated between the target size and the risk of adverse events. Substantial variation among different centers' reported outcomes have prevented us from making toxicity-risk predictions. Cognitive dysfunction in children is largely seen for whole brain doses of >or=18 Gy. No substantial evidence has shown that RT induces irreversible cognitive decline in adults within 4 years of RT.

Assessing neurotoxicity from the low-dose radiation component of radiosurgery using magnetic resonance spectroscopy.

The aim of the study was to determine if biochemical changes indicative of injury, assessed using magnetic resonance spectroscopic imaging (SI), are observed after stereotactic radiosurgery (SRS). The study included patients who underwent SI immediately before and 1, 30, and 90 days following SRS. Short TE spectra (TR/TE 1000/35 ms) were acquired at the SRS isocenter with a 2D PRESS-CSI sequence on a single 1.5 T scanner. The SRS isodose lines were overlaid on the magnetic resonance imaging slice utilized for SI data acquisition. N-Acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were computed for multiple voxels located between the 25 and 50 cGy isodose lines (low dose) and the 200 and 350 cGy isodose lines (medium dose). An analysis of variance and paired t-tests compared metabolite levels at different time points. Twelve patients were enrolled, although 3 were excluded secondary to poor spectral data quality or deviations from the prescribed SI protocol. The median number of voxels analyzed from the low- and medium-dose region was 7 and 4, respectively. No significant changes in metabolite peak height ratios over time were seen in the low-dose region, for either NAA/Cr (P = .89) or Cho/Cr (P = .85). There was no difference in Cho/Cr peak height ratios in the medium-dose region (P = .62). There was an increase in the NAA/Cr peak height ratio in the medium-dose region between day -1 and day +30 (P = .003), followed by a decline to baseline between days +30 and +90 (P = .03). We did not observe a significant decline in NAA/Cr or change in Cho/Cr peak heights in uninvolved brain parenchyma after SRS.