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Purpose Radiation therapy is an effective modality for pain management of symptomatic bone metastases. We update the previous meta-analyses of randomized trials comparing single fraction to multiple fractions of radiation therapy in patients with uncomplicated bone metastases. Methods A literature search was conducted in Ovid Medline, Embase, and Cochrane Central Register. Ten new randomized trials were identified since 2010, five with adequate and appropriate data for inclusion, resulting in a total of 29 trials that were analyzed. Forest plots based on each study’s odds ratios were computed using a random effects model and the Mantel–Haenszel statistic. Results In intention-to-treat analysis, the overall response rate was similar in patients for single fraction treatments (61%; 1867/3059) and those for multiple fraction treatments (62%; 1890/3040). Similarly, complete response rates were nearly identical in both groups (23% vs 24%, respectively). Re-treatment was significantly more frequent in the single fraction treatment arm, with 20% receiving additional treatment to the same site versus 8% in the multiple fraction treatment arm ( p  < 0.01). No significant difference was seen in the risk of pathological fracture at the treatment site, rate of spinal cord compression at the index site, or in the rate of acute toxicity. Conclusion Single fraction and multiple fraction radiation treatment regimens continue to demonstrate similar outcomes in pain control and toxicities, but re-treatment is more common for single fraction treatment patients. [ABSTRACT FROM AUTHOR]

PURPOSE: A majority of patients enrolled in hospice have advanced cancer. Most of them are burdened by symptoms related to uncontrolled tumor growth. Although palliative radiation therapy (RT) is highly effective, only 1% of hospice patients are ever referred. Commonly cited concerns include high treatment cost, burden of travel for multiple visits, and a perceived reluctance of radiation oncologists to deliver single-fraction RT. METHODS: A clinic offering affordable RT to patients in hospice was developed to simplify the intake, reduce cost, and minimize travel to a single visit. The goal was to evaluate, simulate and plan treatment, and treat patients with a single fraction of palliative RT within a 4-hour period. RESULTS: The initial 18-month experience is reported in this Health Information Portability and Accountability Act-compliant report that was approved by the Viriginia Commonwealth University Institutional Review Board. Eight referrals were received from local hospice agencies that had not referred any patients in previous years. A telephone screening process avoided unnecessary travel for two patients who were not candidates for RT. Two additional patients who were evaluated with a same-day computed tomography simulation were not good candidates for RT. Ultimately, four patients were successfully treated with single-fraction palliative RT of 8 Gy. None had to disenroll from hospice. CONCLUSION: This novel program increased access to palliative RT for patients in hospice who would otherwise not have been referred. The main challenge identified was a need for ongoing educational activities at hospice agencies where staff turnover may be high and understanding about palliative RT can be limited. [ABSTRACT FROM AUTHOR]

Purpose: To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Methods and Materials: Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately and committed to an initial management approach. Results: In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT)3 receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Conclusions: Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual patient risk assessment and to refine antiemetic guideline management recommendations. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Radiotherapy is an important treatment modality for pain control in patients with bone metastases. Stereotactic body radiation therapy (SBRT), which allows delivering a much higher dose per fraction while sparing critical structures compared to conventional external beam radiotherapy (cEBRT), has become more widely used, especially in the oligometastatic setting. Randomized controlled trials (RCTs) comparing the pain response rate of SBRT and cEBRT for bone metastases have shown conflicting results, as have four recent systematic reviews with meta-analyses of these trials. Possible reasons for the different outcomes between these reviews include differences in methodology, which trials were included, and the endpoints examined and how they were defined. We suggest ways to improve analysis of these RCTs, particularly performing an individual patient-level meta-analysis since the trials included heterogeneous populations. The results of such studies will help guide future investigations needed to validate patient selection criteria, optimize SBRT dose schedules, include additional endpoints (such as the time to onset of pain response, durability of pain response, quality of life (QOL), and side effects of SBRT), and better assess the cost-effectiveness and trade-offs of SBRT compared to cEBRT. An international Delphi consensus to guide selection of optimal candidates for SBRT is warranted before more prospective data is available.

Background and Objective: The 30-day expected mortality rate is frequently used as a metric to determine which patients benefit from palliative radiation treatment (RT). We conducted a narrative review to examine whether its use as a metric might be appropriate for patient selection., Methods: A literature review was conducted to identify relevant studies that highlight the benefits of palliative RT in timely symptom management among patients with a poor performance status, the accuracy of predicting survival near the end of life and ways to speed up the process of RT administration through rapid response clinics., Key Content and Findings: Several trials have demonstrated substantial response rates for pain and/or bleeding by four weeks and sometimes within the first two weeks after RT. Models of patient survival have limited accuracy, particularly for predicting whether patients will die within the next 30 days. Dedicated Rapid Access Palliative RT (RAPRT) clinics, in which patients are assessed, simulated and treated on the same day, reduce the number of patient visits to the radiation oncology department and hence the burden on the patient as well as costs., Conclusions: Single-fraction palliative RT should be offered to eligible patients if they are able to attend treatment and could potentially benefit from symptom palliation, irrespective of predicted life expectancy. We discourage the routine use of the 30-day mortality as the only metric to decide whether to offer RT. More common implementation of RAPRT clinics could result in a significant benefit for patients of all life expectancies, but particularly those having short ones.

Background: Optimal management of metastatic spinal cord compression (MSCC) improves functional outcomes in patients with metastatic disease. This survey study evaluated management of MSCC by Veterans Health Administration (VHA) radiation oncologists (ROs), to determine whether management of MSCC correlates with American College of Radiology (ACR) guidelines, and to compare times to initiation of treatment between surgery and radiotherapy (RT)., Methods: Surveys emailed to 79 VHA ROs included questions on steroid use, surgical care, palliative care, fractionation of irradiation, re-irradiation, and management of common MSCC case scenarios. Follow-up phone calls were made to encourage survey participation. Descriptive statistics and chi-square testing were done to show significant associations., Results: The survey yielded an 81.0% response rate; 79.4% of ROs had read the ACR Appropriateness Criteria® Spinal Bone Metastases. The majority (87.3%) prefer 30 Gy/10 fractions for MSCC, and all respondents recommend steroid therapy in conjunction with RT. When used, RT was more often initiated within 24 hours than was neurosurgery (83.9% vs. 34.5%, P<0.001). All ROs report use of palliative care services. Re-irradiation is given by 66.1%: 30.7% with stereotactic body radiation therapy (SBRT), 17.7% using intensity modulated radiation therapy (IMRT), and 17.7% using conventional RT. For the case scenarios, most respondents' (>75%) management concurred with ACR guidelines., Conclusions: The majority of VHA ROs are familiar with the ACR Appropriateness Criteria® Spinal Bone Metastases and practice accordingly. Treatment within 24 hours is more likely when RT is the primary modality compared to when surgical decompression precedes RT.

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., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To present evidence-based guidelines for radiation therapy in treating glioblastoma not arising from the brainstem., Methods and Materials: The American Society for Radiation Oncology (ASTRO) convened the Glioblastoma Guideline Panel to perform a systematic literature review investigating the following: (1) Is radiation therapy indicated after biopsy/resection of glioblastoma and how does systemic therapy modify its effects? (2) What is the optimal dose-fractionation schedule for external beam radiation therapy after biopsy/resection of glioblastoma and how might treatment vary based on pretreatment characteristics such as age or performance status? (3) What are ideal target volumes for curative-intent external beam radiation therapy of glioblastoma? (4) What is the role of reirradiation among glioblastoma patients whose disease recurs following completion of standard first-line therapy? Guideline recommendations were created using predefined consensus-building methodology supported by ASTRO-approved tools for grading evidence quality and recommendation strength., Results: Following biopsy or resection, glioblastoma patients with reasonable performance status up to 70 years of age should receive conventionally fractionated radiation therapy (eg, 60 Gy in 2-Gy fractions) with concurrent and adjuvant temozolomide. Routine addition of bevacizumab to this regimen is not recommended. Elderly patients (≥70 years of age) with reasonable performance status should receive hypofractionated radiation therapy (eg, 40 Gy in 2.66-Gy fractions); preliminary evidence may support adding concurrent and adjuvant temozolomide to this regimen. Partial brain irradiation is the standard paradigm for radiation delivery. A variety of acceptable strategies exist for target volume definition, generally involving 2 phases (primary and boost volumes) or 1 phase (single volume). For recurrent glioblastoma, focal reirradiation can be considered in younger patients with good performance status., Conclusions: Radiation therapy occupies an integral role in treating glioblastoma. Whether and how radiation therapy should be applied depends on characteristics specific to tumor and patient, including age and performance status., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Radiation oncologists were surveyed to determine how accessible advanced radiation delivery modalities are within the VHA., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.

Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. However, pain flare, nausea and vomiting are common adverse effects associated with this treatment. The management of pain flare and radiation-induced nausea and vomiting (RINV) are important endpoints in palliative care. Our report documents the incidence, clinical importance, and advances in the management of these two adverse-effects. We recommend that antiemetic prophylaxis be given based on emetic risk category as outlined in the American Society of Clinical Oncology (ASCO) guidelines. Newer antiemetics investigated in the chemotherapy setting should also be studied in the radiation setting. As there are no guidelines for the use of pain flare prophylaxis at present, further research in this area is needed.

This report examines the literature on palliative training in the current medical school curriculum. A literature search was conducted to identify relevant articles. Physicians and medical students both report feeling that their training in end-of-life care and in palliative issues is lacking. The literature expresses concerns about the varied and non-uniform approach to palliative care training across medical schools. The authors recommend the development of more palliative training assessment tools in order to aid in the standardization of curriculum involving end-of-life care. In addition, increased exposure to dying patients will aid students in building comfort with palliative care issues. Such a goal may be accomplished through required clerkships or other similar programs.

The prognosis of patients with bone metastases has improved with the advent of increasingly effective systemic treatment and better supportive care. A growing number of bone metastases patients now outlive the duration of benefits from their initial treatment of radiotherapy (RT) while some patients fail to initially respond to RT. As such, re-irradiation (re-RT) may be required. The current review updates the literature on findings in the area of re-RT. In particular, the recent publication of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Symptom Control (SC20) trial shows that an 8 Gy treatment in a single fraction for re-RT is non-inferior and less toxic than 20 Gy in multiple fractions. Furthermore, patients responding to re-RT have experienced superior quality of life (QoL) and complain of less functional interference from pain; this provides a strong case in support of bone metastases patients being offered re-treatment. However, despite such findings, some specific patients will never respond to initial radiation or re-RT. New evidence suggests significant differences in bone markers between responders and non-responders, thus opening the possibility for further research into the use of such biomarkers for predicting prognosis and for the guidance of consequent treatment decisions.

Physician estimates of patients' survival times have historically been inaccurate. In particular, physicians have often been overly optimistic in their predictions. Our review begins by documenting some of the literature addressing these concerns and proceeds to a discussion of prognostic models that have been created to aid physicians in providing more accurate estimates. We then discuss new findings showing survival to be influenced by particular treatment factors. Given such findings, currently existing prognostic models are now incomplete. However, with the abundance of evidence-based treatment options in a wide variety of patient populations, we propose that radiation oncologists need no longer rely so heavily on the precise prognostic capacity of survival models. Patients of different age demographics and survival prognoses benefit from palliative radiation treatment. More specifically, our report documents studies which show that for uncomplicated bone metastases, a single 8 Gy fraction of radiation is an equally effective tool for palliation regardless of whether a patient will have a short or long duration of survival. In addition we discuss evidence-based treatment options for patients with complicated bone metastases, lung and brain metastases. Further research is required to incorporate treatment factors in future survival prediction models.

Purpose: To provide guidance to physicians and patients with regard to the use of adjuvant external beam radiation therapy (RT) in locally advanced non-small cell lung cancer (LA NSCLC) based on available medical evidence complemented by consensus-based expert opinion., Methods and Materials: A panel authorized by the American Society for Radiation Oncology (ASTRO) Board of Directors and Guidelines Subcommittee conducted 2 systematic reviews on the following topics: (1) indications for postoperative adjuvant RT and (2) indications for preoperative neoadjuvant RT. Practice guideline recommendations were approved using an a priori-defined consensus-building methodology supported by ASTRO and approved tools for the grading of evidence quality and the strength of guideline recommendations., Results: For patients who have undergone surgical resection, high-level evidence suggests that use of postoperative RT does not influence survival, but optimizes local control for patients with N2 involvement, and its use in the setting of positive margins or gross primary/nodal residual disease is recommended. No high-level evidence exists for the routine use of preoperative induction chemoradiation therapy; however, modern surgical series and a post-hoc Intergroup 0139 clinical trial analysis suggest that a survival benefit may exist if patients are properly selected and surgical techniques/postoperative care is optimized., Conclusions: A consensus and evidence-based clinical practice guideline for the adjuvant radiotherapeutic management of LA NSCLC has been created addressing 2 important questions., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To provide guidance to physicians and patients with regard to the use of definitive external beam radiation therapy (RT) in locally advanced non-small cell lung cancer (LA NSCLC) based on available medical evidence complemented by consensus-based expert opinion., Methods and Materials: A panel authorized by the American Society for Radiation Oncology (ASTRO) Board of Directors and Guidelines Subcommittee conducted 3 systematic reviews on the following topics: (1) ideal radical RT dose fractionation for RT alone; (2) ideal radical RT dose fractionation for chemoradiation; and (3) ideal timing of radical radiation therapy with systemic chemotherapy. Practice guideline recommendations were approved using an a priori-defined consensus-building methodology supported by ASTRO and approved tools for the grading of evidence quality and the strength of guideline recommendations., Results: For patients managed by RT alone, a minimum dose of 60 Gy of RT is recommended. Dose escalation beyond 60 Gy in the context of combined modality concurrent chemoradiation has not been found to be associated with any clinical benefits. In the context of combined modality therapy, chemotherapy and radiation should ideally be given concurrently to maximize survival, local control, and disease response rate., Conclusions: A consensus and evidence-based clinical practice guideline for the definitive radiotherapeutic management of LA NSCLC has been created that addresses 3 important questions., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The most recent systematic review of randomized trials in patients with bone metastases has shown equal efficacy of single fraction (SF) and multiple fraction (MF) palliative radiation therapy in pain relief. It is important to determine the patient population to which the evidence applies. This study aims to examine the eligibility criteria of the studies included in the systematic review to define characteristics of "uncomplicated" bone metastases. Inclusion and exclusion criteria of 21 studies included in the systematic review were compared. Common eligibility criteria were documented in hopes of defining the specific features of a common patient population representative of those in the studies. More than half of the studies included patients with cytological or histological evidence of malignancy. Patients with impending and/or existing pathological fracture, spinal cord compression or cauda equina compression were excluded in most studies. Most studies also excluded patients receiving retreatment to the same site. "Uncomplicated" bone metastases can be defined as: presence of painful bone metastases unassociated with impending or existing pathologic fracture or existing spinal cord or cauda equina compression. Therefore, MF and SF have equal efficacy in patients with such bone metastases.

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.

Radiation therapy is often used to palliate symptoms caused by cancer. Short course, or "hypofractionated" palliative radiation therapy provides equivalent palliation in the setting of non-osseous metastasis or uncontrolled localized cancer while being more convenient and cost-effective than longer courses of radiation. Hypofractionated palliative radiation plays a role in the management of obstruction due to tumor, neurologic symptoms, pain caused by localized bulky disease, and bleeding in patients with primary tumors of the lung, head and neck, bladder, rectum, gynecologic malignancies, and metastasis to the liver, lung and brain. Hypofractionated palliative radiation is well tolerated with minimal and self-limited side effects. The side effects that do occur are generally limited to the body region treated and last from a few days to a few weeks.

Radiotherapy is successful, time efficient, cost effective, and safe means to provide palliative relief for a variety of symptoms suffered by oncology patients. While the value of palliative radiotherapy has been understood for more than century, the radiation oncology specialty has only incompletely embraced its role in this setting. The optimization of palliative oncology requires accurate survival prognostication and a dedication to existing hypofractionated radiotherapy regimens that minimize toxicity and improve patient and caregiver convenience. The future of palliative radiotherapy demands more extensive treatment guidelines that explain the proper use of existing and novel technologies while remaining attentive to a growing population of cancer patients and a limited amount of resources with which to provide them care.

Antibody combination therapeutics (ACTs) are polyvalent biopharmaceuticals that are uniquely suited for the control of complex diseases, including antibiotic resistant infectious diseases, autoimmune disorders and cancers. However, ACTs also represent a distinct manufacturing challenge because the independent manufacture and subsequent mixing of monoclonal antibodies quickly becomes cost prohibitive as more complex mixtures are envisioned. We have developed a virus-free recombinant protein expression platform based on adeno-associated viral (AAV) elements that is capable of rapid and consistent production of complex antibody mixtures in a single batch format. Using both multiplexed immunoassays and cation exchange (CIEX) chromatography, cell culture supernatants generated using our system were assessed for stability of expression and ratios of the component antibodies over time. Cultures expressing combinations of three to ten antibodies maintained consistent expression levels and stable ratios of component antibodies for at least 60 days. Cultures showed remarkable reproducibility following cell banking, and AAV-based cultures showed higher stability and productivity than non-AAV based cultures. Therefore, this non-viral AAV-based expression platform represents a predictable, reproducible, quick and cost effective method to manufacture or quickly produce for preclinical testing recombinant antibody combination therapies and other recombinant protein mixtures.

Management of bone metastasis is a multi-disciplinary effort that involves coordination between several medical specialties. External beam radiation therapy (EBRT) remains a powerful and efficient method of palliating pain and preventing skeletal complications from osseous metastasis. Various fractionation schemes, ranging from 8 Gy in a single dose to 30 Gy in 10 fractions, provide equivalent pain relief as demonstrated by dozens of randomized clinical trials. Toxicity profiles are well established and the treatment is generally well tolerated. Radiopharmaceuticals and high-dose, stereotactic radiation therapy are adjuncts to EBRT whose role is being elucidated through clinical trials. Multiple organizations have compiled guidelines and quality metrics to help refine the role of each modality in the management of painful osseous metastases.

Aim: We sought to survey a large, multi-center patient sample to better characterize/quantify RT utilization at the end of life., Background: Few objective data exist for radiation therapy (RT) delivery at end of life (EOL)., Materials and Methods: Data were retrieved for all patients receiving RT in calendar year 2010 in the Department of Radiation Oncology at Indiana University (IU) and Howard University (HU) hospitals. Specific attention was made of the group of patients receiving RT in the last 30 days of life., Results: A total of 852 patients received all or part of their RT during 2010 (HU: 139, IU: 713). At time of analysis in early 2012, 179 patients had died (21%). Fifty-four patients (6.3% of total; 30% of expired patients) died within 30 days of receiving their last treatment. Twenty patients (2.3% of total; 11.2% of expired patients) received RT within their last week of life. For both sites, the median time until death from completion of therapy was 12.5 days (range 2-30 days)., Conclusions: Radiation in the last month of life is likely to provide minimal palliation or survival benefit. This, coupled with the financial implications, time investment, and physical costs, suggests that physicians and patients should more strongly consider hospice, and minimize duration of palliative RT courses as far as possible. As with chemotherapy, RT utilization at EOL should be considered for collection as an overuse metric.

Purpose: This study explored international radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting (RINV)., Methods: Radiation oncology trainees who were members of the national radiation oncology associations of the USA, Canada, Netherlands, Australia, New Zealand, France, Spain and Singapore completed a Web-based survey. Respondents estimated the risks of nausea and vomiting associated with six standardised radiotherapy-only clinical case vignettes modelled after international anti-emetic guidelines and then committed to prophylactic, rescue or no therapy as an initial management approach for each case., Results: One hundred and seventy-six trainees from 11 countries responded. Only 28 % were aware of any anti-emetic guideline. In general, risk estimates and management approaches for the high-risk and minimal risk cases varied less and were more in line with guideline standards than were estimates and approaches for the moderate- and low-risk cases. Prophylactic therapy was the most common approach for the high-risk and a moderate-risk case (83 and 71 % of respondents respectively), while rescue therapy was the most common approach for a second moderate-risk case (69 %), two low-risk cases (69 and 76 %) and a minimal risk case (68 %). A serotonin receptor antagonist was the most commonly recommended prophylactic agent. On multivariate analysis, a higher estimated risk of nausea predicted for recommending prophylactic therapy, and a lower estimated risk of nausea predicted for recommending rescue therapy., Conclusions: Radiation oncology trainee risk estimates and recommended management approaches for RINV clinical case vignettes varied and matched guideline standards more often for high-risk and minimal risk cases than for moderate- and low-risk cases. Risk estimates of nausea specifically were strong predictors of management decisions.

Abstract The spine is a common site of involvement in patients with bone metastases. Apart from pain, hypercalcemia, and pathologic fracture, progressive tumor can result in neurologic deterioration caused by spinal cord compression or cauda equina involvement. The treatment of spinal bone metastases depends on histology, site of disease, extent of epidural disease, extent of metastases elsewhere, and neurologic status. Treatment recommendations must weigh the risk-benefit profile of external beam radiation therapy (EBRT) for the particular individual's circumstance, including neurologic status, performance status, extent of spinal disease, stability of the spine, extra-spinal disease status, and life expectancy. Patients with spinal instability should be evaluated for surgical intervention. Research studies are needed that evaluate the combination or sequencing of localized therapies with systemic therapies including chemotherapy, hormonal therapy (HT), osteoclast inhibitors (OI), and radiopharmaceuticals. The roles of stereotactic body radiation therapy (SBRT) in the management of spinal oligometastasis, radioresistant spinal metastasis, and previously irradiated but progressive spinal metastasis are emerging, but more research is needed to validate the findings from retrospective studies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

The management of painful bone metastases requires multidisciplinary care, with external beam radiation therapy (EBRT) providing relief that is effective and time efficient. Patients with bone metastases may require interventions including surgical decompression, osteoclast inhibitors, radiopharmaceuticals, and kyphoplasty or vertebroplasty, though EBRT should be included in the care of most of these patients, as well. Recent treatment-guideline publications for bone metastases greatly define the appropriate use of EBRT for this patient group, and they create a means by which treatment approaches may serve as quality measures of radiotherapy departments.

Bone metastases are a common manifestation of malignancy, and external beam radiotherapy (EBRT) effectively and safely palliates the pain caused by this clinical circumstance. The myriad of EBRT dosing schemes and complexities involved with coordinating radiotherapy with other interventions necessitated the need for bone metastases treatment guidelines. Here we compare and contrast the bone metastases radiotherapy treatment guidelines recently published by the American Society for Radiation Oncology (ASTRO) and the American College of Radiology (ACR). These evaluations acknowledge current controversies in treatment approaches, they evaluate the nuances of ASTRO and ACR task force decision-making regarding standard approaches to care, and they project the upcoming research results that may clarify approaches to palliative radiotherapy for bone metastases. The results of these two dedicated radiotherapy guidelines are compared to the brief mentions of radiotherapy for bone metastases in the National Comprehensive Cancer Network (NCCN) guidelines. Finally, the paper describes how treatment guidelines may influence patterns of care and reimbursement by their use as quality measures by groups such as the National Quality Forum (NQF).

Bone is one of the most common sites of metastatic spread of malignancy, with possible deleterious effects including pain, hypercalcemia, and pathologic fracture. External beam radiotherapy (EBRT) remains the mainstay for treatment of painful bone metastases. EBRT may be combined with other local therapies like surgery or with systemic treatments like chemotherapy, hormonal therapy, osteoclast inhibitors, or radiopharmaceuticals. EBRT is not commonly recommended for patients with asymptomatic bone metastases unless they are associated with a risk of pathologic fracture. For those who do receive EBRT, appropriate fractionation schemes include 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, or a single 8 Gy fraction. Single fraction treatment maximizes convenience, while fractionated treatment courses are associated with a lower incidence of retreatment. The appropriate postoperative dose fractionation following surgical stabilization is uncertain. Reirradiation with EBRT may be safe and provide pain relief, though retreatment might create side effect risks which warrant its use as part of a clinical trial. All patients with bone metastases should be considered for concurrent management by a palliative care team, with patients whose life expectancy is less than six months appropriate for hospice evaluation. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Purpose: Quality in cancer care is an issue that has come to the forefront over the past decade. Although the American Society of Clinical Oncology has developed extensive quality metrics and goals, such as limiting chemotherapy being provided within the last 14 days of a patient's life, there are no similar quality metrics, and few data, in the field of radiation oncology., Methods: In this study, morbidity and mortality records from 2008 to 2011 were reviewed for patients at Indiana University who received radiation therapy (RT) within 30 days of death; 63 patients met those criteria., Results: Analysis showed that 22.2% of patients had Karnofsky Performance Status Scale scores >80, whereas 66.7% of patients had scores < 60. Just over half of patients (52%) were still on treatment at death, and more than half of patients (54%) had completed less than half of their original RT plans. Six patients had their final treatments on the days of their deaths, and another 43 patients had their last treatments within 10 days of death. Forty-eight percent of patients received RT for less than one-fifth of their final month of life and 21% for more than half of their last month alive., Conclusions: These data are valuable in ongoing discussions of RT use at the end of life, especially as related to hospice underutilization., (Copyright © 2012 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 American Society for Radiation Oncology and American College of Radiology. All rights reserved.)

Palliative radiotherapy has been prescribed since shortly after the discovery of the x-ray in the late 1800s, and it provides symptom relief that is successful, time-efficient, and cost-effective. Although palliative radiotherapy is worthwhile in a wide variety of clinical circumstances, there are situations where it is less worthwhile. We contrast the effective use of palliative radiotherapy with its ineffective use because of issues related to the patient, treatment, or health care system.

Appropriate imaging modalities for screening, staging, and surveillance of patients with suspected and documented metastatic disease to bone include (99m)Tc bone scanning, MRI, CT, radiography, and 2-[(18)F]fluoro-2-deoxyglucose-PET. Clinical scenarios reviewed include asymptomatic stage 1 breast carcinoma, symptomatic stage 2 breast carcinoma, abnormal bone scan results with breast carcinoma, pathologic fracture with known metastatic breast carcinoma, asymptomatic well-differentiated and poorly differentiated prostate carcinoma, vertebral fracture with history of malignancy, non-small-cell lung carcinoma staging, symptomatic multiple myeloma, osteosarcoma staging and surveillance, and suspected bone metastasis in a pregnant patient. No single imaging modality is consistently best for the assessment of metastatic bone disease across all tumor types and clinical situations. In some cases, no imaging is indicated. The recommendations contained herein are the result of evidence-based consensus by the ACR Appropriateness Criteria((R)) Expert Panel on Musculoskeletal Radiology.

Spinal cord compression (SCC) from spinal metastasis is a common complication in cancer and if left untreated, permanent paraplegia or quadriplegia will occur. Timely diagnosis is crucial in preventing permanent neurologic damage. Once SCC is suspected, diagnostic imaging of the spine should be obtained to confirm diagnosis. Treatment consists of surgery, radiotherapy or a combination of both. Stereotactic body radiotherapy has also been incorporated into the management of SCC. The treatment decision should be made based on multiple factors, including tumor histology, retropulsion of bony fragments, performance status of the patient and status of extraspinal systemic disease. This review focuses on the pathophysiology, diagnosis and management of SCC.

Changes in population dynamics will require increased end-of-life cancer care in the coming years. Palliative radiotherapy successfully relieves symptoms of advanced cancer, with the most common indication for its use being uncomplicated painful bone metastases. Single-fraction radiotherapy provides successful, time-efficient and cost-effective management of bone metastases. Newer technologies, such as stereotactic body radiotherapy, hold promise for some patients with spine metastases, although their niche has not been properly defined and their use outside of a protocol setting is inappropriate. Surgery should be considered for circumstances of completed or impending pathologic fracture, spinal instability, or spinal cord compression in patients who have adequate performance status and prognosis. Multiple sites of painful metastases may be treated with injectible radiopharmaceuticals or hemibody radiation. The future developments in palliative radiotherapy for bone metastases will mirror several forces affecting all of medicine, including resource allocation, the adoption of clinical guidelines and the integration of newer technologies.