William F. Hartsell

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 Medicines 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.

International Patterns of Practice in Palliative Radiotherapy for Painful Bone Metastases: Evidence-Based Practice?

PURPOSE Multiple randomized controlled trials have demonstrated the equivalence of multifraction and single-fraction (SF) radiotherapy for the palliation of painful bone metastases (BM). However, according to previous surveys, SF schedules remain underused. The objectives of this study were to determine the current patterns of practice internationally and to investigate the factors influencing this practice. METHODS AND MATERIALS The members of three global radiation oncology professional organizations (American Society for Radiology Oncology [ASTRO], Canadian Association of Radiation Oncology [CARO], Royal Australian and New Zealand College of Radiologists) completed an Internet-based survey. The respondents described what radiotherapy dose fractionation they would recommend for 5 hypothetical cases describing patients with single or multiple painful BMs from breast, lung, or prostate cancer. Radiation oncologists rated the importance of patient, tumor, institution, and treatment factors, and descriptive statistics were compiled. The chi-square test was used for categorical variables and the Student t test for continuous variables. Logistic regression analysis identified predictors of the use of SF radiotherapy. RESULTS A total of 962 respondents, three-quarters ASTRO members, described 101 different dose schedules in common use (range, 3 Gy/1 fraction to 60 Gy/20 fractions). The median dose overall was 30 Gy/10 fractions. SF schedules were used the least often by ASTRO members practicing in the United States and most often by CARO members. Case, membership affiliation, country of training, location of practice, and practice type were independently predictive of the use of SF. The principal factors considered when prescribing were prognosis, risk of spinal cord compression, and performance status. CONCLUSION Despite abundant evidence, most radiation oncologists continue to prescribe multifraction schedules for patients who fit the eligibility criteria of previous randomized controlled trials. Our results have confirmed a delay in the incorporation of evidence into practice for palliative radiotherapy for painful bone metastases.

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.

Therapeutic Guidelines for the Treatment of Bone Metastasis: A Report from the American College of Radiology Appropriateness Criteria Expert Panel on Radiation Oncology

Bone metastases remain a therapeutic challenge because of the diversity of the problems they cause, the relative paucity of data regarding their treatment, and the necessity for management by a multidisciplinary palliative care team. The American College of Radiology convened an Appropriateness Criteria Expert Panel on Radiation Oncology for the treatment of bone metastasis to create representative clinical case scenarios and then rank the appropriate use of treatment modalities as well as the most reasonable radiotherapy dose schema and treatment planning methods. Here we present both the resulting Appropriateness Criteria and the rationale for making these decisions. The treatment recommendations are placed within the larger framework of the role of radiation in palliative care by discussing the efficiency of palliative radiotherapy schedules, cost effectiveness issues, and the need for additional research regarding the proper multidisciplinary care of patients with symptomatic bone metastasis.

Economic analysis of radiation therapy oncology group 97-14: multiple versus single fraction radiation treatment of patients with bone metastases.

Introduction:Radiation Therapy Oncology Group 97-14 concluded that a single fraction of radiation was as effective in relieving pain as multiple fractions in the treatment of patients with bone metastases. A statistically significant higher retreatment rate, however, was noted in patients undergoing a single fraction treatment. The purpose of the analysis was to determine whether multiple fraction treatment is cost-effective in treating patients with bone metastasis, by preventing further retreatment. Methods and Material:A Markov model was used to evaluate the cost-effectiveness of 30 Gy in 10 fractions in comparison with 8 Gy in 1 fraction. Transition probabilities, cost, and utilities were obtained from the clinical trial. Costs and outcomes were not discounted because of the short time line for the study. Results:The expected mean cost and quality-adjusted survival in months for patients receiving 8 Gy in 1 fraction and 30 Gy in 10 fractions was

Single-fraction radiotherapy versus multifraction radiotherapy for palliation of painful vertebral bone metastases-equivalent efficacy, less toxicity, more convenient: a subset analysis of Radiation Therapy Oncology Group trial 97-14.

998 and 7.26 months and

Treatment of medulloblastoma in adults

2316 and 9.53 months, respectively. The incremental cost-effectiveness ratio was

Should multicentric disease be an absolute contraindication to the use of breast-conserving therapy?

6973/quality-adjusted life year. The results were sensitive to the utility of the posttreatment state for both single and multiple fraction treatments. Conclusion:Single fraction treatment was the less expensive treatment in the treatment of patients with bone metastasis treated on Radiation Therapy Oncology Group 97-14.

Can serum markers be used to predict acute and late toxicity in patients with lung cancer? Analysis of RTOG 91-03.

The Radiation Therapy Oncology Group (RTOG) trial 97‐14 revealed no difference between radiation delivered for painful bone metastases at a dose of 8 gray (Gy) in 1 fraction (single‐fraction radiotherapy [SFRT]) and 30 Gy in 10 fractions (multifraction radiotherapy [MFRT]) in pain relief or narcotic use 3 months after randomization. SFRT for painful vertebral bone metastases (PVBM) has not been well accepted, possibly because of concerns about efficacy and toxicity. In the current study, the authors evaluated the subset of patients that was treated specifically for patients with PVBM.

Can physicians accurately predict survival time in patients with metastatic cancer? Analysis of RTOG 97-14

Seventeen adult patients with medulloblastoma were treated at Rush-Presbyterian-St. Lukes Medical Center and affiliated hospitals between 1969 and 1986. All patients had a surgical procedure (total excision in seven patients, partial resection in nine patients, and biopsy alone in one patient) followed by radiation therapy to the craniospinal axis. The 5-year actuarial survival rate is 77% with a disease-free survival of 58%. Five patients have relapsed in the posterior fossa, one in the brain parenchyma, and two in osseous sites. Two of the local relapses occurred more than 4 years after initial treatment. Patients undergoing “total” resection of the tumor fared better than those with partial resection or biopsy only. Local failure was uncommon with posterior fossa doses > 55 Gy, and there was a trend toward better local control when the radiation therapy was completed in less than 7 weeks. The histologic indicators of poor outcome were necrosis, high mitotic index, and “classical” histologic appearance.