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Walker GV, Shirvani SM, Borghero Y, Callister MD, Chamberlain DD, Grade EJ, Khan MK, Kumar R, Richmond JG, Roberts TJ, Likhacheva AO. Palliation or Prolongation? The Impact of a Peer-Review Intervention on Shortening Radiotherapy Schedules for Bone Metastases. J Oncol Pract 2018; 14:e513-e516. [PMID: 30059272 DOI: 10.1200/jop.18.00042] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Shorter fractionation radiation regimens for palliation of bone metastases result in lower financial and social costs for patients and their caregivers and have similar efficacy as longer fractionation schedules, although practice patterns in the United States show poor adoption. We investigated whether prospective peer review can increase use of shorter fractionation schedules. METHODS In June 2016, our practice mandated peer review of total dose and fractionation for all patients receiving palliative treatment during our weekly chart rounds. We used descriptive statistics and Fisher's exact test to compare lengths of treatment of uncomplicated bone metastases before and after implementation of the peer review process. RESULTS Between July 2015 and December 2016, a total of 242 palliative treatment courses were delivered, including 105 courses before the peer review intervention and 137 after the intervention. We observed greater adoption of shorter fractionation regimens after the intervention. The use of 8 Gy in one fraction increased from 2.8% to 13.9% of cases postadoption. Likewise, the use of 20 Gy in five fractions increased from 25.7% to 32.8%. The use of 30 Gy in 10 fractions decreased from 55.2% to 47.4% ( P = .002), and the use of ≥ 11 fractions decreased from 16.2% before the intervention to 5.8% after ( P = .006). CONCLUSION Prospective peer review of palliative regimens for bone metastases can lead to greater adoption of shorter palliative fractionation schedules in daily practice, in accordance with national guidelines. This simple intervention may therefore benefit patients and their caregivers as well as provide value to the health care system.
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Affiliation(s)
- Gary V Walker
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Shervin M Shirvani
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Yerko Borghero
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Matthew D Callister
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Daniel D Chamberlain
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Emily J Grade
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Mohamed K Khan
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Rachit Kumar
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jeffrey G Richmond
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Terence J Roberts
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Anna O Likhacheva
- Banner MD Anderson Cancer Center, Gilbert, AZ; and The University of Texas MD Anderson Cancer Center, Houston, TX
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2
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Efficacy of multiple fraction conventional radiation therapy for painful uncomplicated bone metastases: A systematic review. Radiother Oncol 2017; 122:323-331. [DOI: 10.1016/j.radonc.2016.12.031] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 12/03/2016] [Accepted: 12/28/2016] [Indexed: 11/18/2022]
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Sigurdardottir KR, Oldervoll L, Hjermstad MJ, Kaasa S, Knudsen AK, Løhre ET, Loge JH, Haugen DF. How are palliative care cancer populations characterized in randomized controlled trials? A literature review. J Pain Symptom Manage 2014; 47:906-914.e17. [PMID: 24018205 DOI: 10.1016/j.jpainsymman.2013.06.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Revised: 06/05/2013] [Accepted: 06/14/2013] [Indexed: 02/08/2023]
Abstract
CONTEXT The difficulties in defining a palliative care patient accentuate the need to provide stringent descriptions of the patient population in palliative care research. OBJECTIVES To conduct a systematic literature review with the aim of identifying which key variables have been used to describe adult palliative care cancer populations in randomized controlled trials (RCTs). METHODS The data sources used were MEDLINE (1950 to January 25, 2010) and Embase (1980 to January 25, 2010), limited to RCTs in adult cancer patients with incurable disease. Forty-three variables were systematically extracted from the eligible articles. RESULTS The review includes 336 articles reporting RCTs in palliative care cancer patients. Age (98%), gender (90%), cancer diagnosis (89%), performance status (45%), and survival (45%) were the most frequently reported variables. A large number of other variables were much less frequently reported. CONCLUSION A substantial variation exists in how palliative care cancer populations are described in RCTs. Few variables are consistently registered and reported. There is a clear need to standardize the reporting. The results from this work will serve as the basis for an international Delphi process with the aim of reaching consensus on a minimum set of descriptors to characterize a palliative care cancer population.
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Affiliation(s)
- Katrin Ruth Sigurdardottir
- European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Sunniva Centre for Palliative Care, Haraldsplass Deaconess Hospital, Bergen, Norway; Regional Centre of Excellence for Palliative Care, Western Norway, Haukeland University Hospital, Bergen, Norway.
| | - Line Oldervoll
- European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Røros Rehabilitation Centre, Røros, Norway
| | - Marianne Jensen Hjermstad
- European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Regional Centre for Excellence in Palliative Care, South Eastern Norway, Oslo University Hospital, Oslo, Norway
| | - Stein Kaasa
- European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Oncology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Anne Kari Knudsen
- European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Oncology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Erik Torbjørn Løhre
- Department of Oncology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Jon Håvard Loge
- European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; National Resource Centre for Late Effects After Cancer Treatment, Oslo University Hospital, Oslo, Norway
| | - Dagny Faksvåg Haugen
- European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Regional Centre of Excellence for Palliative Care, Western Norway, Haukeland University Hospital, Bergen, Norway
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McQuay HJ, Collins SL, Carroll D, Moore RA, Derry S, Cochrane Pain, Palliative and Supportive Care Group. WITHDRAWN: Radiotherapy for the palliation of painful bone metastases. Cochrane Database Syst Rev 2013; 2013:CD001793. [PMID: 24271498 PMCID: PMC6564087 DOI: 10.1002/14651858.cd001793.pub2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
This review is out of date and has been withdrawn. The content of the review may be of historical interest to readers. The editorial group responsible for this previously published document have withdrawn it from publication.
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Affiliation(s)
- Henry J McQuay
- University of OxfordPain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics)West Wing (Level 6)John Radcliffe HospitalOxfordOxfordshireUKOX3 9DU
| | - Sally L Collins
- University of OxfordNuffield Department of Obstetrics and GynaecologyThe Fetal Medicine Unit, Level 6, Women's CentreJohn Radcliffe HospitalOxfordOxfordshireUKOX3 9DU
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Thavarajah N, Zhang L, Wong K, Bedard G, Wong E, Tsao M, Danjoux C, Barnes E, Sahgal A, Dennis K, Holden L, Lauzon N, Chow E. Patterns of practice in the prescription of palliative radiotherapy for the treatment of bone metastases at the Rapid Response Radiotherapy Program between 2005 and 2012. ACTA ACUST UNITED AC 2013; 20:e396-405. [PMID: 24155637 DOI: 10.3747/co.20.1457] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE We examined whether patterns of practice in the prescription of palliative radiation therapy for bone metastases had changed over time in the Rapid Response Radiotherapy Program (rrrp). METHODS After reviewing data from August 1, 2005, to April 30, 2012, we analyzed patient demographics, diseases, organizational factors, and possible reasons for the prescription of various radiotherapy fractionation schedules. The chi-square test was used to detect differences in proportions between unordered categorical variables. Univariate logistic regression analysis and the simple Fisher exact test were also used to determine the factors most significant to choice of dose-fractionation schedule. RESULTS During the study period, 2549 courses of radiation therapy were prescribed. In 65% of cases, a single fraction of radiation therapy was prescribed, and in 35% of cases, multiple fractions were prescribed. A single fraction of radiation therapy was more frequently prescribed when patients were older, had a prior history of radiation, or had a prostate primary, and when the radiation oncologist had qualified before 1990. CONCLUSIONS For patients with bone metastasis, a single fraction of radiation therapy was prescribed with significantly greater frequency.
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Affiliation(s)
- N Thavarajah
- Rapid Response Radiotherapy Program, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON
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Molloy AP, O’Toole GC. Orthopaedic perspective on bone metastasis. World J Orthop 2013; 4:114-119. [PMID: 23878778 PMCID: PMC3717243 DOI: 10.5312/wjo.v4.i3.114] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2012] [Revised: 03/21/2013] [Accepted: 06/06/2013] [Indexed: 02/06/2023] Open
Abstract
The incidence of cancer is increasing worldwide, with the advent of a myriad of new treatment options, so is the overall survival of these patients. However, from an orthopaedic perspective, there comes the challenge of treating more patients with a variety of metastatic bone lesions. The consequences of such lesions can be significant to the patient, from pain and abnormal blood results, including hypercalcemia, to pathological fracture. Given the multiple options available, the treatment of bone metastasis should be based on a patient-by patient manner, as is the case with primary bone lesions. It is imperative, given the various lesion types and locations, treatment of bone metastasis should be performed in an individualised manner. We should consider the nature of the lesion, the effect of treatment on the patient and the overall outcome of our decisions. The dissemination of primary lesions to distant sites is a complex pathway involving numerous cytokines within the tumour itself and the surrounding microenvironment. To date, it is not fully understood and we still base a large section of our knowledge on Pagets historic “seed and soil” theory. As we gain further understanding of this pathway it will allow us develop more medical based treatments. The treatment of primary cancers has long been provided in a multi-disciplinary setting to achieve the best patient outcomes. This should also be true for the treatment of bone metastases. Orthopaedic surgeons should be involved in the multidisciplinary treatment of such patients given that there are a variety of both surgical fixation methods and non-operative methods at our disposal.
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Nieder C, Pawinski A, Dalhaug A. Continuous controversy about radiation oncologists' choice of treatment regimens for bone metastases: should we blame doctors, cancer-related features, or design of previous clinical studies? Radiat Oncol 2013; 8:85. [PMID: 23574944 PMCID: PMC3643865 DOI: 10.1186/1748-717x-8-85] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2013] [Accepted: 04/07/2013] [Indexed: 12/25/2022] Open
Abstract
Recent studies from Italy, Japan and Norway have confirmed previous reports, which found that a large variety of palliative radiotherapy regimens are used for painful bone metastases. Routine use of single fraction treatment might or might not be the preferred institutional approach. It is not entirely clear why inter-physician and inter-institution differences continue to persist despite numerous randomized trials, meta-analyses and guidelines, which recommend against more costly and inconvenient multi-fraction regimens delivering total doses of 30 Gy or more in a large number of clinical scenarios. In the present mini-review we discuss the questions of whether doctors are ignoring evidence-based medicine or whether we need additional studies targeting specifically those patient populations where recent surveys identified inconsistent treatment recommendations, e.g. because of challenging disease extent. We identify open questions and provide research suggestions, which might contribute to making radiation oncology practitioners more confident in selecting the right treatment for the right patient.
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Affiliation(s)
- Carsten Nieder
- Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, 8092, Norway.
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Lutz S, Lo SS, Chow E, Sahgal A, Hoskin P. Radiotherapy for metastatic bone disease: current standards and future prospectus. Expert Rev Anticancer Ther 2011; 10:683-95. [PMID: 20470001 DOI: 10.1586/era.10.32] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
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.
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Affiliation(s)
- Stephen Lutz
- Blanchard Valley Regional Cancer Center, 15990 Medical Drive South, Findlay, OH 45840, USA.
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Radiation Therapy in the Management of Cancer Pain. Pain Manag 2011. [DOI: 10.1016/b978-1-4377-0721-2.00034-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Abstract
BACKGROUND: Bone metastases are common in breast cancer patients. Radiotherapy is safe and effective. This review aimes to contribute to the definition of the appropriate radiation regimens for different endpoints. MATERIAL AND METHODS: Information was compiled by searching PubMed and MEDLINE databases including early-release publications. When possible, primary sources were quoted. Full articles were obtained. References were checked for additional material when appropriate. RESULTS: Randomized trials and meta-analyses demonstrated that single-fraction radiotherapy with 1 × 8 Gy is as effective for pain relief as multi-fraction regimens such as 5 × 4 Gy or 10 × 3 Gy. Re-irradiation for recurrent pain is required more often after single-fraction radiotherapy. Re-irradiation with another single fraction is safe and effective. Multi-fraction long-course radiotherapy such as 10 × 3 Gy leads to better re-calcification and better local control of metastatic spinal cord compression (MSCC). Because both re-calcification and MSCC recurrences occur only several months after radiotherapy, long-course radiotherapy is particularly appropriate for patients with a favorable survival prognosis. CONCLUSIONS: For uncomplicated painful bone metastases, single-fraction radiotherapy with 1 × 8 Gy may be considered the standard regimen. If re-calcification is a major goal, longer-course radiotherapy (i.e. 10 × 3 Gy) should be used. For MSCC, 10 × 3 Gy is preferable for patients with a favorable survival prognosis.
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Affiliation(s)
- Dirk Rades
- Department of Radiation Oncology, University of Lübeck, Germany
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12
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13
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Time course of pain relief in patients treated with radiotherapy for cancer pain: a prospective study. Clin J Pain 2010; 26:38-42. [PMID: 20026951 DOI: 10.1097/ajp.0b013e3181b0c82c] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES The purpose of this prospective study was to analyze time course of pain relief by radiotherapy for cancer pain. METHODS A total of 91 patients with painful bone metastases were treated by radiotherapy with a median total dose of 46 Gy. Pain of the irradiated site was assessed using a numerical rating scale (pain score: 0 to 10) once a week from the beginning of radiotherapy (day 1) for about 5 weeks. RESULTS In time course analysis of the 91 cases, the mean (+/-SD) pain scores at day 5, day 12, day 19, day 26, day 33, and day 40 were 7.8 (+/-1.6), 5.3 (+/-2.5), 3.5 (+/-2.5), 2.4 (+/-2.5), 1.6 (+/-2.1), and 1.1 (+/-1.9), respectively, and mean pain score was significantly reduced with time from the start of radiotherapy (P<0.001: repeated measure ANOVA). Mean pain score was significantly reduced every week by d33 (P<0.05: d5 vs. d12, d12 vs. d19, d19 vs. d26, and d26 vs. d33). Complete pain relief was obtained in 45/91 (49%) cases, and partial (> or =50%) pain relief was obtained in 83/91 (91%) cases. The mean time to obtain 50% pain relief was 13 days. The mean time to obtain complete pain relief (n=45) was 24 days. Doses of analgesics were reduced in 28/64 (44%) cases at the end of radiotherapy. DISCUSSION Telling approximate time course of pain relief seems to reduce patients' anxiety, and knowing time course of pain relief seems to be useful to determine optimal dose of analgesics that changes according to the course.
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International patterns of practice in palliative radiotherapy for painful bone metastases: evidence-based practice? Int J Radiat Oncol Biol Phys 2009; 75:1501-10. [PMID: 19464820 DOI: 10.1016/j.ijrobp.2008.12.084] [Citation(s) in RCA: 144] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2008] [Revised: 12/20/2008] [Accepted: 12/29/2008] [Indexed: 11/24/2022]
Abstract
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.
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Pradier O, Bouchekoua M, Albargach N, Muller M, Malhaire JP. Radiothérapie des métastases osseuses : quel est le meilleur schéma de radiothérapie ? Cancer Radiother 2008; 12:837-41. [DOI: 10.1016/j.canrad.2008.06.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2008] [Accepted: 06/05/2008] [Indexed: 11/27/2022]
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Lagrange JL, Pan C, Calitchi É, Diana C, Muresan M, Wu JF, El Monkles H, Wang XW, Lu H. Radiothérapie pratique des métastases osseuses symptomatiques. ACTA ACUST UNITED AC 2008. [DOI: 10.1016/j.rhum.2008.02.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Metastatic Cancer to Bone. Oncology 2007. [DOI: 10.1007/0-387-31056-8_95] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Management of Cancer Pain. Oncology 2007. [DOI: 10.1007/0-387-31056-8_82] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Cozad SC. Radiation Therapy in the Management of Cancer Pain. Pain Manag 2007. [DOI: 10.1016/b978-0-7216-0334-6.50034-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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Coen JJ, Zietman AL, Kaufman DS, Shipley WU. Benchmarks achieved in the delivery of radiation therapy for muscle-invasive bladder cancer. Urol Oncol 2007; 25:76-84. [PMID: 17208144 DOI: 10.1016/j.urolonc.2006.05.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Radiation therapy has a multifaceted role in the treatment of muscle-invasive bladder cancer, from being a component of bladder sparing regimens to adjuvant therapy for patients after partial cystectomy, to palliative treatment in patients with metastatic disease. Here, we review the techniques currently used and the settings in which these techniques are applied. Advances in imaging and radiation delivery have allowed for definition of more precise treatment volumes, permitting the delivery of higher tumor doses and lesser doses to critical targets. Better tumor control, fewer therapeutic complications, and better quality of life outcomes are anticipated. In the United States, the most rapidly growing use of radiation in the treatment of bladder cancer is as a component of selective bladder conservation. It uses trimodality therapy, consisting of a maximal transurethral resection followed by concurrent chemotherapy and radiation. Careful cystoscopic surveillance by an experienced urologist ensures a prompt cystectomy at the fist sign of treatment failure. The majority of patients retain a well-functioning bladder with no survival decrement. Radiation therapy is also used as adjuvant therapy after partial cystectomy in select patients. In this setting, it decreases the risk of local or incisional recurrence. It is also used in patients with pelvic recurrences after cystectomy, often combined with concurrent chemotherapy. Radiation is a very effective palliative agent for patients with locally advanced or metastatic disease. It can palliate bleeding and pain for patients with local progression or alleviate pain from bony metastases.
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Affiliation(s)
- John J Coen
- Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
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van der Linden YM, Steenland E, van Houwelingen HC, Post WJ, Oei B, Marijnen CAM, Leer JWH. Patients with a favourable prognosis are equally palliated with single and multiple fraction radiotherapy: results on survival in the Dutch Bone Metastasis Study. Radiother Oncol 2006; 78:245-53. [PMID: 16545474 DOI: 10.1016/j.radonc.2006.02.007] [Citation(s) in RCA: 121] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2005] [Revised: 02/08/2006] [Accepted: 02/23/2006] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND PURPOSE In the prospectively, randomized Dutch Bone Metastasis Study on the effect of a single fraction of 8 Gy versus 24 Gy in six fractions on painful bone metastases, 28% of the patients survived for more than 1 year. Purpose of the present study was to analyze the palliative effect of radiotherapy in long-term surviving patients, and to identify prognostic factors for survival. MATERIAL AND METHODS Response rates were compared in all patients surviving>52 weeks. The Cox proportional hazards model stratified by primary tumour was used for multivariate (MV) analyses of prognostic factors for survival. RESULTS In 320 patients surviving>52 weeks, responses were 87% after 8 Gy and 85% after 24 Gy (P=0.54). Duration of response and progression rates were similar. For all primary tumours, prognostic factors for survival were a good Karnofsky Performance Score, no visceral metastases, and non-opioid analgesics intake (all factors, MV P<0.001). CONCLUSIONS Single fraction radiotherapy should be the standard dose schedule for all patients with painful bone metastases, including patients with an expected favourable survival. General prognosticators as the Karnofsky Performance Score and metastatic tumour load are useful in predicting survival.
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Chow E, Hoskin PJ, Wu J, Roos D, van der Linden Y, Hartsell W, Vieth R, Wilson C, Pater J. A Phase III International Randomised Trial Comparing Single with Multiple Fractions for Re-irradiation of Painful Bone Metastases: National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) SC 20. Clin Oncol (R Coll Radiol) 2006; 18:125-8. [PMID: 16523812 DOI: 10.1016/j.clon.2005.11.014] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Abstract
Palliative radiation therapy is considered when the incurable cancer patient has symptoms specifically related to a malignancy that may be relieved by localized treatment of the primary tumor or metastatic lesions. Developing a treatment plan with radiation in the palliative setting may be more difficult than the curative setting, where there are clear guidelines for many situations. Radiation therapy has been used successfully in the management of a variety of pain syndromes. Radiation also has proven effective in the management of other tumor-related symptoms, including bleeding, neurologic compromise, dysphagia, and airway obstruction. Palliative radiation can be delivered using a variety of techniques: external beam radiation therapy, intraluminal brachytherapy (radioactive seed delivery), and systemic radionucleotides.
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Affiliation(s)
- Christopher Dolinsky
- Department of Radiation Oncology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, 2 Donner Building, Philadelphia, PA 19104, USA.
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Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M, Suh JH, Demas WF, Movsas B, Petersen IA, Konski AA, Cleeland CS, Janjan NA, DeSilvio M. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst 2005; 97:798-804. [PMID: 15928300 DOI: 10.1093/jnci/dji139] [Citation(s) in RCA: 531] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Radiation therapy is effective in palliating pain from bone metastases. We investigated whether 8 Gy delivered in a single treatment fraction provides pain and narcotic relief that is equivalent to that of the standard treatment course of 30 Gy delivered in 10 treatment fractions over 2 weeks. METHODS A prospective, phase III randomized study of palliative radiation therapy was conducted for patients with breast or prostate cancer who had one to three sites of painful bone metastases and moderate to severe pain. Patients were randomly assigned to 8 Gy in one treatment fraction (8-Gy arm) or to 30 Gy in 10 treatment fractions (30-Gy arm). Pain relief at 3 months after randomization was evaluated with the Brief Pain Inventory. The Wilcoxon-Mann-Whitney test was used to compare response to treatment in terms of pain and narcotic relief between the two arms and for each stratification variable. All statistical comparisons were two-sided. RESULTS There were 455 patients in the 8-Gy arm and 443 in the 30-Gy arm; pretreatment characteristics were equally balanced between arms. Grade 2-4 acute toxicity was more frequent in the 30-Gy arm (17%) than in the 8-Gy arm (10%) (difference = 7%, 95% CI = 3% to 12%; P = .002). Late toxicity was rare (4%) in both arms. The overall response rate was 66%. Complete and partial response rates were 15% and 50%, respectively, in the 8-Gy arm compared with 18% and 48% in the 30-Gy arm (P = .6). At 3 months, 33% of all patients no longer required narcotic medications. The incidence of subsequent pathologic fracture was 5% for the 8-Gy arm and 4% for the 30-Gy arm. The retreatment rate was statistically significantly higher in the 8-Gy arm (18%) than in the 30-Gy arm (9%) (P < .001). CONCLUSIONS Both regimens were equivalent in terms of pain and narcotic relief at 3 months and were well tolerated with few adverse effects. The 8-Gy arm had a higher rate of re-treatment but had less acute toxicity than the 30-Gy arm.
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Szumacher E, Llewellyn-Thomas H, Franssen E, Chow E, DeBoer G, Danjoux C, Hayter C, Barnes E, Andersson L. Treatment of bone metastases with palliative radiotherapy: Patients’ treatment preferences. Int J Radiat Oncol Biol Phys 2005; 61:1473-81. [PMID: 15817353 DOI: 10.1016/j.ijrobp.2004.08.035] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2004] [Revised: 06/21/2004] [Accepted: 08/13/2004] [Indexed: 11/17/2022]
Abstract
PURPOSE To determine the proportion of patients undergoing palliative radiotherapy (RT) for bone pain who would like to participate in the decision-making process, and to determine their choice of palliative RT regimen (2000 cGy in five fractions vs. 800 cGy in one fraction) for painful bone metastases. METHODS AND MATERIALS Eligible patients were approached and all patients agreeing to participate provided written informed consent. Patients' decisional preferences were studied using a five-statement preference instrument. A decision board was used to help patients decide their preferred palliative RT regimen. Factors influencing patients' choices were studied using a visual analog scale. RESULTS A total of 101 patients were enrolled in the study (55 women and 46 men). The preferences for decision-making were as follows: 30 active, 47 collaborative, and 24 passive. Most (55 [76%] of 72) patients favored one fraction of palliative RT (95% confidence interval, 65-86%). Patients were more likely to select the 800 cGy in one fraction because of the convenience of the treatment plan (odds ratio, 1.024; 95% confidence interval, 1.004-1044) but were less likely to choose it because of the chance of bone fracture (odds ratio, 0.973; 95% confidence interval, 0.947-1.000) compared with 2000 cGy in five fractions. CONCLUSION Most participating patients preferred to decide either by themselves or with the radiation oncologists which treatment option they preferred. An 800-cGy-in-one-fraction regimen was favored, independent of the treated site. The convenience of the treatment plan and the likelihood of bone fracture were the most important factors influencing patients' choice.
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Affiliation(s)
- Ewa Szumacher
- Rapid Response Radiotherapy Program, Bone Metastases Site Group, Department of Radiation Oncology, Toronto Sunnybrook Regional Cancer Centre, University of Toronto, Toronto, ON, Canada.
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Abstract
Radiation is an effective modality to aid in symptom management of patients with metastatic disease. The type and duration of treatment depends on the Karnofsky performance status (KPS) of the patient and type and status of the cancer. Abbreviated treatment regimens may be favored in this patient population. They provide quick palliation without the patient and family spending significant time traveling back and forth to the treatment center. Hypofractionated regimens have been found effective in relieving pain from metastatic bone disease, relieving obstruction from locally advanced lung cancer, bleeding from gynecologic cancers, and hematuria from advanced bladder cancer. More aggressive regimens such as whole-brain radiation therapy (WBRT) and stereotactic radiosurgery may be appropriate for select patients with a good KPS. Radiation has also been found to be effective in palliating recurrent cancer that has already received definitive radiation.
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Affiliation(s)
- Andre Konski
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
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van der Linden YM, Dijkstra SPDS, Vonk EJA, Marijnen CAM, Leer JWH. Prediction of survival in patients with metastases in the spinal column: results based on a randomized trial of radiotherapy. Cancer 2005; 103:320-8. [PMID: 15593360 DOI: 10.1002/cncr.20756] [Citation(s) in RCA: 292] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Adequate prediction of survival is important in deciding on treatment for patients with symptomatic spinal metastases. The authors reviewed 342 patients with painful spinal metastases without neurologic impairment who were treated conservatively within a large, prospectively randomized radiotherapy trial. Response to radiotherapy and prognostic factors for survival were studied. METHODS The data base of the Dutch Bone Metastasis Study was used. Response to treatment and prognostic factors for overall survival (OS) were studied using a Cox regression model. A scoring system was developed to predict OS. RESULTS Responses were noted in 73% of patients. In 3% of patients, spinal cord compression was reported a mean of 3.5 months after randomization. The median OS was 7 months, and significant predictors for survival were Karnofsky performance score, primary tumor (multivariate analysis; both P < 0.001), and the absence of visceral metastases (multivariate analysis; P = 0.02). A scoring system based on these predictors was developed, and 34% of patients were in Group A (median OS = 3.0 months), 48% of patients were in Group B (median OS = 9.0 months), and 18% of patients were in Group C (median OS = 18.7 months). Group C was comprised of patients with breast carcinoma, a good performance, and no visceral metastases. CONCLUSIONS Most patients with spinal metastases have a limited life expectancy and should be treated with caution regarding surgical procedures. Radiotherapy is a safe and effective, noninvasive treatment modality for pain. The new scoring system will enable physicians to select patients who may survive long enough to benefit from more radical treatment.
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Shakespeare TP, Thiagarajan A, Gebski V. Evaluation of the quality of radiotherapy randomized trials for painful bone metastases. Cancer 2005; 103:1976-81. [PMID: 15772960 DOI: 10.1002/cncr.20993] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND The quality of randomized radiotherapy studies investigating the palliation of painful bone metastases has been questioned, with some authors recognizing the potential impact of bias on result interpretation. However, there has been no published comprehensive evaluation of quality assessment. The goals of the current study were to evaluate the quality of randomized studies using a validated checklist and to discuss implications and future directions. METHODS The authors performed a search for studies that could be reliably assessed using the validated quality assessment instrument. Independent assessors scored study quality using the instrument. RESULTS The median quality score of the 17 identified randomized studies was 1 of 5 (range, 0-3). The majority (71%) of points were awarded for the authors describing the study as "randomized." The method of randomization and description of withdrawals and dropouts were scored poorly for most studies. None of the studies were awarded points for allocation concealment (blinding). The overall quality was deemed poor (a score of 0-2) for 16 of 17 (94%) studies. CONCLUSIONS The quality of published randomized evidence comparing efficacy of fractionation schedules for the palliation of bone metastases was suboptimal. As a result of the potential biases present, subjective end points (e.g., retreatment rates) cannot be reliably evaluated. Greater efforts are required by radiation oncology trial groups to improve quality, with a particular focus on developing methods of allocation concealment and comprehensively reporting results.
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van der Linden YM, Lok JJ, Steenland E, Martijn H, van Houwelingen H, Marijnen CAM, Leer JWH. Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment. Int J Radiat Oncol Biol Phys 2004; 59:528-37. [PMID: 15145173 DOI: 10.1016/j.ijrobp.2003.10.006] [Citation(s) in RCA: 210] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2003] [Revised: 09/30/2003] [Accepted: 10/15/2003] [Indexed: 02/03/2023]
Abstract
PURPOSE The Dutch Bone Metastasis Study on the effect on painful bone metastases of 8 Gy single fraction (SF) vs. 24 Gy in multiple fractions (MF) showed 24% retreatment after SF vs. 6% after MF (p < 0.001). The purpose of the present study was to evaluate factors influencing retreatment and its effect on response. METHODS AND MATERIALS The database on all randomized patients was reanalyzed with separately calculated responses to initial treatment and retreatment. RESULTS Response to initial treatment was 71% after SF vs. 73% after MF (p = 0.84). Retreatment raised response to 75% for SF; MF remained unaltered (p = 0.54). The response status after initial treatment did not predict occurrence of retreatment: 35% SF vs. 8% MF nonresponders and 22% SF vs. 10% MF patients with progressive pain were retreated. Logistic regression analyses showed the randomization arm and the pain score before retreatment to significantly predict retreatment (p < 0.001). Retreatment for nonresponders was successful in 66% SF vs. 33% MF patients (p = 0.13). Retreatment for progression was successful in 70% SF vs. 57% MF patients (p = 0.24). CONCLUSIONS With or without the effect of retreatment, SF and MF radiotherapy provided equal palliation for painful bone metastases. Irrespective of response to initial treatment, physicians were more willing to retreat after a single fraction. Overall, retreatment was effective in 63% of retreated patients.
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Sze WM, Shelley MD, Held I, Wilt TJ, Mason MD. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy--a systematic review of randomised trials. Clin Oncol (R Coll Radiol) 2004; 15:345-52. [PMID: 14524489 DOI: 10.1016/s0936-6555(03)00113-4] [Citation(s) in RCA: 192] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Recent randomised studies have reported that single fraction radiotherapy is as effective as multifraction radiotherapy in relieving pain caused by bone metastasis. However, there are concerns about the higher re-treatment rates and the efficacy of preventing future complications, such as pathological fracture and spinal cord compression, by single fraction radiotherapy. A systematic review of randomised studies, examining the effectiveness of single fraction radiotherapy versus multiple fraction radiotherapy for metastatic bone pain relief and prevention of bone complications, was conducted to help answer this controversy. Randomised studies comparing single fraction radiotherapy with multifraction radiotherapy on metastatic bone pain were identified. The analyses were performed using intention-to-treat principle. The results were pooled using meta-analysis to estimate the effect of treatment on pain response, re-treatment rate, pathological fracture rate and spinal cord compression rate. Twelve trials involving 3621 sites were included in the meta-analysis. The overall pain-response rates for single fraction radiotherapy and multifraction radiotherapy were 60% (1080/1814) and 59% (1060/1807), respectively, giving an odds ratio (OR) of 1.03 (95% confidence interval [CI] 0.90-1.19), indicating no difference between the two radiotherapy schedules. There was also no difference in complete pain response rates for single fraction radiotherapy (34% [508/1476]) and multifraction radiotherapy (32% [475/1473]), with an OR of 1.10 (950% CI 0.94-1.30). Patients treated by single fraction radiotherapy had a higher re-treatment rate, with 21.5% (267/1240) requiring re-treatment compared with 7.4% (91/1236) of patients in the multifraction radiotherapy arm (OR 3.44 [95% CI 2.67-4.43]). The pathological fracture rate was also higher in single fraction radiotherapy arm patients. Three per cent (37/1240) of patients treated by single fraction radiotherapy developed pathological fracture compared with 1.6% (20/1236) for those treated by multifraction radiotherapy (OR 1.82 [95% CI 1.06-3.11]). The spinal cord compression rates were similar for both arms (OR 1.41 [95% CI 0.72-2.75]). Single fraction radiotherapy was as effective as multifraction radiotherapy in relieving metastatic bone pain. However, the re-treatment rate and pathological fracture rate were higher after single fraction radiotherapy. Studies with quality of life and health economic end points are warranted to find out the optimal treatment option.
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Affiliation(s)
- W M Sze
- Departament of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, PR China.
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Sze WM, Shelley M, Held I, Mason M. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy - a systematic review of the randomised trials. Cochrane Database Syst Rev 2004; 2002:CD004721. [PMID: 15106258 PMCID: PMC6599833 DOI: 10.1002/14651858.cd004721] [Citation(s) in RCA: 78] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Recent randomised studies reported that single fraction radiotherapy was as effective as multifraction radiotherapy in relieving pain due to bone metastasis. However, there are concerns about the higher re-treatment rates and the efficacy of preventing future complications such as pathological fracture and spinal cord compression by single fraction radiotherapy. OBJECTIVES To undertake a systematic review and meta-analysis of single fraction radiotherapy versus multifraction radiotherapy for metastatic bone pain relief and prevention of bone complications. SEARCH STRATEGY Trials were identified through MEDLINE, EMBASE, Cancerlit, reference lists of relevant articles and conference proceedings. Relevant data was extracted. SELECTION CRITERIA Randomised studies comparing single fraction radiotherapy with multifraction radiotherapy on metastatic bone pain DATA COLLECTION AND ANALYSIS The analyses were performed using intention-to-treat principle. The results were pooled using meta-analysis to estimate the effect of treatment on pain response, re-treatment rate, pathological fracture rate and spinal cord compression rate. MAIN RESULTS Eleven trials that involved 3435 patients were identified. Of 3435 patients, 52 patients were randomised more than once for different painful bone metastasis sites. Altogether, 3487 painful sites were randomised. The trials included patients with painful bone metastases of any primary sites, but were mainly prostate, breast and lung. The overall pain response rates for single fraction radiotherapy and multifraction radiotherapy were 60% (1059/1779) and 59% (1038/1769) respectively, giving an odds ratio of 1.03 (95% confidence interval [CI], 0.89 - 1.19) indicating no difference between the two radiotherapy schedules. There was also no difference in complete pain response rates for single fraction radiotherapy (34% [497/1441]) and multifraction radiotherapy (32% [463/1435]) with an odds ratio of 1.11 (95%CI 0.94-1.30). Patients treated by single fraction radiotherapy had a higher re-treatment rate with 21.5% (267/1240) requiring re-treatment compared to 7.4% (91/1236) of patients in the multifraction radiotherapy arm (odds ratio 3.44 [95%CI 2.67-4.43]). The pathological fracture rate was also higher in single fraction radiotherapy arm patients. Three percent (37/1240) of patients treated by single fraction radiotherapy developed pathological fracture compared to 1.6% (20/1236) for those treated by multifraction radiotherapy (odds ratio 1.82 [95%CI 1.06-3.11]). The spinal cord compression rates were similar for both arms (odds ratio 1.41 [95%CI 0.72-2.75]). Repeated analyses excluding dropout patients gave similar results. REVIEWERS' CONCLUSIONS Single fraction radiotherapy was as effective as multifraction radiotherapy in relieving metastatic bone pain. However, the re-treatment rate and pathological fracture rates were higher after single fraction radiotherapy. Studies with quality of life and health economic end points are warranted to find out the optimal treatment option.
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Affiliation(s)
- Wai Man Sze
- Pamela Youde Nethersole Eastern HospitalClinical OncologyLG1 East Block3 Lok Man RoadHong KongChina
| | - Mike Shelley
- Velindre NHS TrustCochrane Prostatic Diseases and Urological Cancers Unit, Research DeptVelindre RoadWhitchurchCardiffUKCF4 7XL
| | - Ines Held
- Cardiff University and North East Wales NHS TrustNephrologyCardiffUK
| | - Malcolm Mason
- Velindre HospitalClinical OncologyWhitchurchCardiffUKCF4 7XL
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Abstract
Radiation therapy plays a major role in the treatment of patients with bone metastases. The primary goals of treatment include pain relief and relief of neurologic symptoms, if present. Approximately 70% of patients will achieve pain relief with palliative external beam radiotherapy. Improvement in the severity of pain may occur within as few as 48 to 72 hours of initiation of therapy, but in some patients significant relief of pain may not occur for 4 weeks after completion of therapy. Treatment schemes ranging from 800 cGy in a single treatment to 3000 cGy in 10 treatments have not been shown to result in major differences in outcome. Treatment decisions must be individualized based on factors such as the patient's performance status, life expectancy, location of the lesion, and size of area to be treated. External beam radiotherapy is recommended after surgical treatment of pathologic fractures or impending fractures to decrease the need for a second surgical procedure and improve the patient's functional outcome. External beam radiotherapy continues to be an important component of the palliative treatment of bone metastases. Its integration with newer therapeutic modalities such as vertebroplasty and radiofrequency ablation currently is being studied.
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Affiliation(s)
- Deborah A Frassica
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Radiation Oncology Center, Lutherville, MD 21093, USA.
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Barton MB, Jacob SA, Gebsky V. Utility-adjusted analysis of the cost of palliative radiotherapy for bone metastases. AUSTRALASIAN RADIOLOGY 2003; 47:274-8. [PMID: 12890248 DOI: 10.1046/j.1440-1673.2003.01175.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Palliative radiotherapy is effective in the treatment of bone metastases but is under-utilized, possibly because it is perceived to be expensive. We performed a cost-utility analysis of palliative radiotherapy for bone metastases, evaluating both the actual cost of radiotherapy as well as its impact on quality of life by adjusting for the variation in response to treatment. Hospital records between July 1991 and July 1996 were reviewed to ascertain the number of patients treated with palliative radiotherapy for bone metastases, the average number of fields of radiation delivered to each patient and the average duration of survival. Partial and complete response rates to palliative radiotherapy were obtained from a review of all published randomized controlled trials of radiation treatment of bone metastases. Utility values were assigned to the response rates, and an overall adjusted response rate to radiotherapy was derived. The cost of delivering a field of radiation was calculated. The total cost was divided by the total number of response months to give a utility-adjusted cost per month of palliative radiotherapy. The utility-adjusted cost per month of palliative radiotherapy of bone metastases was found to be AUS dollars 100 per month or AUS dollars 1200 per utility-adjusted life-year. This study demonstrates that, contrary to popular perception, palliative radiotherapy is a cost-effective treatment modality for bone metastases.
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Affiliation(s)
- Michael B Barton
- Collaboration for Cancer Outcomes Research and Evaluation, Liverpool Health Service, New South Wales, Australia.
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Shakespeare TP, Lu JJ, Back MF, Liang S, Mukherjee RK, Wynne CJ. Patient preference for radiotherapy fractionation schedule in the palliation of painful bone metastases. J Clin Oncol 2003; 21:2156-62. [PMID: 12775741 DOI: 10.1200/jco.2003.10.112] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE The radiotherapeutic management of painful bone metastases is controversial, with several institutional and national guidelines advocating use of single-fraction radiotherapy. We aimed to determine patient choice of fractionation schedule after involvement in the decision-making process by use of a decision board. PATIENTS AND METHODS Advantages and disadvantages of two fractionation schedules (24 Gy in six fractions v 8 Gy in one fraction) used in the randomized Dutch Bone Metastasis Study were discussed with patients using a decision board. Patients were asked to choose a fractionation schedule, to give reasons for their choice, and to indicate level of satisfaction with being involved in decision making. RESULTS Sixty-two patients were entered. Eighty-five percent (95% confidence interval, 74% to 93%) chose 24 Gy in six fractions over 8 Gy in one fraction (P <.0005). Variables including age, sex, performance status, tumor type, pain score, and paying class were not significantly related to patient choice. Multiple fractionation was chosen for lower re-treatment rates (92%) and fewer fractures (32%). Single-fraction treatment was chosen for cost (11%) and convenience (89%). Eighty-four percent of patients expressed positive opinions about being involved in the decision-making process. CONCLUSION Decision board instruments are feasible and acceptable in an Asian population. The vast majority of patients preferred 24 Gy fractionated radiotherapy compared with a single fraction of 8 Gy. These results indicate the need for further research in this important area and serve to remind both clinicians and national or institutional policy makers of the importance of individual patient preference in treatment decision making.
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Affiliation(s)
- Thomas P Shakespeare
- Radiotherapy Centre, The Cancer Institute, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074.
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Chow E, Wu JSY, Hoskin P, Coia LR, Bentzen SM, Blitzer PH. International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Radiother Oncol 2003; 64:275-80. [PMID: 12242115 DOI: 10.1016/s0167-8140(02)00170-6] [Citation(s) in RCA: 226] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
PURPOSE To reach a consensus on a set of optimal endpoint measurements for future external beam radiotherapy trials in bone metastases. METHODS An International Bone Metastases Consensus Working Party invited principal investigators and individuals with a recognized interest in bone metastases to participate in the two surveys and a panel meeting on their preference of choice of optimal endpoints. RESULTS Consensus has been reached on the following: (a) eligibility criteria for future trials; (b) pain and analgesic assessments; (c) radiation techniques; (d) follow-up and timing of assessments; (e) parameters at follow-up; (f) endpoints; (g) re-irradiation; and (h) statistical analysis. CONCLUSIONS Based on the available literature and the clinical experience of the working party members, an acceptable set of endpoints has been agreed upon for future clinical trials to promote consistency in reporting. It is intended that the consensus will be re-examined every 5 years. Areas of further research were identified.
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Affiliation(s)
- Edward Chow
- Department of Radiation Oncology, Toronto Sunnybrook Regional Cancer Centre, University of Toronto, Ontario, Canada
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Wu JSY, Wong R, Johnston M, Bezjak A, Whelan T. Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 2003; 55:594-605. [PMID: 12573746 DOI: 10.1016/s0360-3016(02)04147-0] [Citation(s) in RCA: 352] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
PURPOSE To compare pain relief among various dose-fractionation schedules of localized radiotherapy (RT) in the treatment of painful bone metastases. METHODS AND MATERIALS A systematic search for randomized trials of localized RT on bone metastases using different dose fractionations was performed using Medline (1966 to February 2001) and other sources. The primary outcomes of interest were complete and overall pain relief. The studies were divided into three groups: comparisons of doses given as a single fraction, single vs. multiple fractions, and comparisons of doses given as multiple fractions. The complete and overall pain responses for studies comparing single vs. multiple fractions were pooled. Exploratory analyses of the dose-response relationship, using the biologic effective dose (alpha/beta = 10), were performed using results from all three groups of trials. RESULTS Two trials comparing single vs. single, eight trials comparing single vs. multiple, and six trials comparing multiple vs. multiple fractions were included. The complete and overall response rates from studies comparing single-fraction RT (median 8 Gy, range 8-10 Gy) against multifraction RT (median 20 Gy in 5 fractions, range 20 Gy in 5 fractions to 30 Gy in 10 fractions) were homogeneous and allowed pooling of data. Of 3260 randomized patients in seven studies, 539 (33.4%) of 1613 and 523 (32.3%) of 1618 patients achieved a complete response after single and multifraction RT, respectively, giving a risk ratio of 1.03 (95% confidence interval 0.94-1.14; p = 0.5). The overall response rate was in favor of single-fraction RT (1011 [62.1%] of 1629) compared with multifraction (958 [58.7%] of 1631; risk ratio 1.05, 95% confidence interval 1.00-1.11, p = 0.04), reaching statistical significance. However, when the analysis was restricted to evaluated patients alone, the overall response rates were similar for single fraction and multifraction RT, at 1011 (72.7%) of 1391 and 958 (72.5%) of 1321, respectively (risk ratio 1.00; p = 0.9). Exploratory analyses by biologic effective dose did not reveal any dose-response relationship among the fractionation schedules used (single 8 Gy to 40 Gy in 15 fractions). Of the other results and observations reported in the trials, only the re-irradiation rates were consistently different between the treatment arms (more frequent re-irradiation in lower dose arms among trials reporting re-irradiation rates). CONCLUSION Meta-analysis of reported randomized trials shows no significant difference in complete and overall pain relief between single and multifraction palliative RT for bone metastases. No dose-response relationship could be detected by including data from the multifraction vs. multifraction trials. Additional data are needed to evaluate the role of re-irradiation and the impact of RT on other treatment end points such as quality of life.
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Affiliation(s)
- Jackson Sai-Yiu Wu
- Division of Radiation Oncology, Hamilton Regional Cancer Centre, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
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Fine PG. Palliative radiation therapy in end-of-life care: evidence-based utilization. Am J Hosp Palliat Care 2002; 19:166-70. [PMID: 12026039 DOI: 10.1177/104990910201900307] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Perry G Fine
- Department of Anesthesiology, Pain Management Center, University of Utah, Salt Lake City, USA
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40
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Barton R, Robinson G, Gutierrez E, Kirkbride P, McLean M. Palliative radiation for vertebral metastases: the effect of variation in prescription parameters on the dose received at depth. Int J Radiat Oncol Biol Phys 2002; 52:1083-91. [PMID: 11958905 DOI: 10.1016/s0360-3016(01)02738-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
PURPOSE To assess the effect of prescription parameters on the dose received by the spine during palliative radiotherapy. MATERIALS AND METHODS In a survey, members of the Canadian Association of Radiation Oncologists were asked to define their prescription parameters for vertebral metastases. The depth of the spinal canal and vertebral body at 8 spinal levels was measured in 20 magnetic resonance imaging studies (MRIs). Survey results were applied to the measurements to assess the dose received at depth. The depth of spinal structures assessed at simulation and by diagnostic imaging was compared. RESULTS Prescriptions were most commonly to D(max) 3 cm or 5 cm using 60Co-6MV photons delivering 8-30 Gy in 1-10 fractions. Mean depths from MRI were: posterior spinal canal, 5.5 cm; anterior spinal canal, 6.9 cm; and anterior vertebral body, 9.6 cm. Application of the prescription parameters from the survey to these measurements showed a wide range in the dose at depth with variation in technique. Depths measured at simulation correlated well with diagnostic imaging. CONCLUSION The spinal canal and vertebral body lie >5 cm beneath the skin, and the dose received varies by up to 50% with changes in prescription depth. We suggest a suitable prescription point for vertebral metastases and a method for determining this at simulation.
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Affiliation(s)
- Rachael Barton
- Palliative Radiation Oncology Program, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada.
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Wu JSY, Bezjak A, Chow E, Kirkbride P. Primary treatment endpoint following palliative radiotherapy for painful bone metastases: need for a consensus definition? Clin Oncol (R Coll Radiol) 2002; 14:70-7. [PMID: 11899906 DOI: 10.1053/clon.2001.0012] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVES To compare and contrast the definitions of primary treatment endpoints in randomized studies of dose-fractionation schedules for treating bone metastases and to identify basic characteristics of treatment endpoint that may require consensus among investigators. METHODS Randomized controlled trials (RCTs) of various dose-fractionation schedules for painful bone metastases, published between 1980 and 1999, and on-going trials whose protocols were available, were systematically reviewed based on the following features of the primary treatment endpoint: (i) degree of pain relief; (ii) timing of the pain response assessment; (iii) effect of co-interventions on pain relief; (iv) the reduction of analgesic as a treatment response; and (v) quantification of response duration. RESULTS Ten published RCTs (each sampled over 100 patients), plus two current trial protocols were reviewed. Five of the 12 studies defined any reduction in pain score as the primary endpoint. Three trials defined response at pre-determined time points, whereas eight studies attributed pain improvement at any time during follow-up to the effect of radiotherapy. No trial incorporated effect of systemic treatments on response. Only two trials incorporated analgesic scores into the primary endpoint criteria, although several trials reported results of combined pain and analgesic relief. Eight trials reported duration of response. Three provided some estimation of duration with respect to survival: two of them employing actuarial time to pain progression, and one calculated the ratio of pain response to median survival duration (percent net relief). Quality of life was measured in four of 12 studies, as secondary endpoint. CONCLUSION Although available data suggest similarity in pain relief among various dose-fractionation schedules, accurate and consistent description of the degree of benefit from radiotherapy is lacking. While pain relief is a consistent primary treatment goal among randomized trials, a consensus on several important features of treatment endpoint is needed in order to establish common grounds for future trials in palliative radiotherapy.
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Affiliation(s)
- Jackson S Y Wu
- Department of Radiation Oncology, Hamilton Regional Cancer Centre, McMaster University, Ontario, Canada.
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Jeremic B. Single fraction external beam radiation therapy in the treatment of localized metastatic bone pain. A review. J Pain Symptom Manage 2001; 22:1048-58. [PMID: 11738168 DOI: 10.1016/s0885-3924(01)00359-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Bone metastases are a frequent complication of cancer, and frequently cause pain. Indications for radiotherapy for bone metastases include pain, risk for pathologic fracture, and neurological complications arising from spinal cord compression, nerve root pain or cranial nerve involvement. There are numerous fractionation patterns of external beam radiation therapy for painful bone metastasis, both fractionated schedules and single fraction regimens. All prospective randomized trials that evaluated differences in the outcomes associated with various fractionated regimens versus single fraction regimens unequivocally showed that single fraction regimens (mostly 8 Gy) are at least equal with various fractionated regimens. The single fraction regimens have an additional advantage of being more convenient to both patients and hospitals. However, there are still numerous questions that are left unanswered in these trials, such as the "optimal" single fraction that should be used, the possibility for retreatment, and prognostic factors that may help identify those patients more likely to respond to a single fraction radiation therapy in the treatment of painful bone metastasis.
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Affiliation(s)
- B Jeremic
- Department of Radiation Oncology, University Hospital, Tuebingen, Germany
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43
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Maisano R, Pergolizzi S, Cascinu S. Novel therapeutic approaches to cancer patients with bone metastasis. Crit Rev Oncol Hematol 2001; 40:239-50. [PMID: 11738947 DOI: 10.1016/s1040-8428(01)00092-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
Bone metastases are a common event in advanced cancer. Breast, lung, prostate and thyroid neoplasms have striking osteotropism. Bone metastatic cancer may be associated with catastrophic consequences for the patients. Therefore, new strategies are warranted in order to reduce the incidence of bone metastases and to palliative established skeletal disease. External beam radiation therapy, endocrine treatments, chemotherapy, bisphosphonates and radioisotopes are all important. Bisphosphonates have become the treatment of choice for tumor-induced hypercalcaemia and more recently they have been used alone or in combination with cytotoxic agents in the palliative treatment of patients with bone metastases. The results are encouraging. Currently, new bisphosphonates that are a hundred times more powerful with respect to clodronate and pamidronate are under investigation. The treatment of metastases to bone and mechanisms of pain relief after radiation therapy are poorly understood. Up to date, there are not standard criteria for the irradiation of bone metastases and bone pain relief may be reached using a variety of fractionation schemes. Radionuclide therapy is the systemic use of radioisotopes for bone pain. It is currently regarded as suitable for comparison with wide-field irradiation, but appears to have major disadvantages in terms of pain relief and toxicity.
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Affiliation(s)
- R Maisano
- IST (Istituto Nazionale per la Ricerca sul Cancro) Genova, Sez. Dec. Messina, Italy.
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44
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Simon JM. [Gross tumor volume and clinical target volume in radiotherapy: bone metastasis]. Cancer Radiother 2001; 5:704-10. [PMID: 11715322 DOI: 10.1016/s1278-3218(01)00128-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Bone is one of the three most favored sites of solid tumor metastasis. Skeletal metastasis may be identified by four clinical imaging methods: plain film radiography, computed tomography scanning, radioisotope scanning, and magnetic resonance imaging. The dose per fraction, total dose, and anatomic distribution of the radiation (dosimetry) are important factors in determining the efficacy and normal tissue tolerance to radiotherapy. Controversies about fractionation of palliative radiotherapy for bone metastasis are steel ongoing. The most commonly used schedules are a single treatment of 8 Gy, 30 Gy in 10 fractions and 20 Gy in 5 fractions. Treatment volumes and safety margins depend on the location and the extent of the bone metastasis, and are also determined by the symptoms felt by the patient.
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Affiliation(s)
- J M Simon
- Centre des tumeurs, groupe hospitalier Pitié-Salpêtrière, 47-83, boulevard de l'hôpital, 75651 Paris, France.
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Affiliation(s)
- O S Nielsen
- Aarhus University Hospital, Department of Oncology, Denmark
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46
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Affiliation(s)
- P J Hoskin
- Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK
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47
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International Bone Metastases Consensus on Endpoint Measurements for Future Clinical Trials: Proceedings of the First Survey and Meeting (Work in Progress) International Bone Metastases Consensus Working Party. Clin Oncol (R Coll Radiol) 2001; 13:82-4. [PMID: 11373883 DOI: 10.1053/clon.2001.9222] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Barton MB, Dawson R, Jacob S, Currow D, Stevens G, Morgan G. Palliative radiotherapy of bone metastases: an evaluation of outcome measures. J Eval Clin Pract 2001; 7:47-64. [PMID: 11240839 DOI: 10.1046/j.1365-2753.2001.00262.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The objective of this study was to identify and evaluate important patient-based outcomes that are specific to the palliative radiotherapy of bone metastases. We first conducted a literature review to identify and evaluate outcomes that are currently in use. To identify outcomes that are important to patients, in-depth patient interviews were conducted. Finally, issues identified through the interviews were quantified through a prospective survey, in which patients completed a questionnaire prior to commencing radiotherapy and again after 6 weeks. In our literature review, we found that there was no standardized definition of either response to radiotherapy or assessment of pain relief. Pain measurement in many studies was undertaken using very simple measures, which could possibly yield inaccurate results. The vast majority of studies did not include quality of life as an endpoint. The patient interviews and survey showed that chronic pain and associated limitation of movement were the disease symptoms causing the most concern. Having a clear, alert mind and being able in self-care were the aspects of daily living given the highest priority. Sustained pain relief and minimizing the risk of future complications were the main priorities relating to radiotherapy treatment. The practical aspects of treatment (travelling distance, remaining at home and brevity of treatment) were of least importance. This study indicates the complexity of evaluating the outcomes of palliative interventions, and confirms the deficiencies of pain relief as the primary end-point. The patient's quality of life is affected by many factors other than pain (such as limited mobility, reduced performance, side effects and impaired role functioning); hence a wider range of end-points is required. Greater sensitivity is required than in currently used end-points. Concurrent diseases as well as concurrent therapies can make it difficult to attribute effects with precision. Unless such factors are considered in research design, the results may prove unreliable.
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Affiliation(s)
- M B Barton
- Division of Radiation Oncology, Westmead Hospital, Australia
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Abstract
Radiation therapy is commonly used to alleviate the pain associated with bone metastases. This article reviews the components of the radiation oncology evaluation. The options for use of ionizing radiation including postoperative treatment, limited-volume external beam radiotherapy, wide-field radiotherapy, and radioisotope therapy are compared and contrasted. Side effects and toxicities of radiotherapy are discussed.
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Affiliation(s)
- D A Frassica
- Division of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland, USA
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Chow E, Danjoux C, Wong R, Szumacher E, Franssen E, Fung K, Finkelstein J, Andersson L, Connolly R. Palliation of bone metastases: a survey of patterns of practice among Canadian radiation oncologists. Radiother Oncol 2000; 56:305-14. [PMID: 10974379 DOI: 10.1016/s0167-8140(00)00238-3] [Citation(s) in RCA: 73] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Palliative radiotherapy constitutes nearly 50% of the workload in radiotherapy. Surveys on the patterns of practice in radiotherapy have been published from North America and Europe. Our objective was to determine the current pattern of practice of radiation oncologists in Canada for the palliation of bone metastases. METHOD A survey was sent to 300 practicing radiation oncologists in Canada. Five case scenarios were presented. The first three were patients with a single symptomatic site: breast cancer patient with pelvic metastasis, lung cancer male with metastasis to L3 and L1, respectively. The last two were breast and prostate cancer patients with multiple symptomatic bone metastases. RESULTS A total of 172 questionnaires were returned (57%) for a total of 860 responses. For the three cases with a single painful bone metastasis, over 98% would prescribe radiotherapy. The doses ranged from a single 8 to 30 Gy in ten fractions. Of the 172 respondents, 117 (68%) would use the same dose fractionation for all three cases, suggesting that they had a standard dose fractionation for palliative radiotherapy. The most common dose fractionation was 20 Gy in five fractions used by 84/117 (72%), and 8 Gy in one fraction by 19/117 (16%). In all five case scenarios, 81% would use a short course of radiotherapy (single 8 Gy, 17%; 20 Gy in five fractions, 64%), while 10% would prescribe 30 Gy in ten fractions. For the two cases with diffuse symptomatic bone metastases, half body irradiation (HBI) and radionuclides were recommended more frequently in prostate cancer than in breast cancer (46/172 vs. 4/172, P<0. 0001; and 93/172 vs. 10/172, P<0.0001, respectively). Strontium was the most commonly recommended radionuclide (98/103=95%). Since systemic radionuclides are not readily available in our health care system, 41/98 (42%) of radiation oncologists who would recommend strontium were not familiar with the dose. Bisphosphonates were recommended more frequently in breast cancer than in prostate cancer 13/172 (8%) vs. 1/172 (0.6%), P=0.001. CONCLUSION Local field external radiotherapy remains the mainstay of therapy, and the most common fractionation for bone metastases in Canada is 20 Gy in five fractions compared with 30 Gy in ten fractions in the US. Despite randomized trials showing similar results for single compared with fractionated radiotherapy, the majority of us still advocate five fractions. The frequency of employing a single fractionation has not changed since the last national survey in 1992. Nearly 70% use a standard dose fractionation to palliate localized painful metastasis by radiotherapy, independent of the site of involvement or tumor type. The pattern of practice of palliative radiotherapy for bone metastases in Canada is different to that reported previously from the US. The reasons why the results of randomized studies on bone metastases have no impact on the patterns of practice are worth exploring.
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Affiliation(s)
- E Chow
- Rapid Response Radiotherapy Program, Toronto-Sunnybrook Regional Cancer Centre, Division of Radiation Oncology, 2075 Bayview Avenue, Ontario, Toronto, Canada M4N 3M5
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