Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial.
*Dose Fractionation; *Radiotherapy; Aged; Analgesics – Therapeutic Use; Analgesics/therapeutic use; Australia; Bone Neoplasms; Bone Neoplasms – Complications; Bone Neoplasms – Radiotherapy; Bone Neoplasms/complications/*radiotherapy/*secondary; Brief Pain Inventory; Canada; Cauda Equina; Chi Square Test; Chi-Square Distribution; Clinical Assessment Tools; Clinical Trials; Computer-Assisted; Computer-Assisted – Adverse Effects; Computer-Assisted/adverse effects; Europe; Female; Fractures; Funding Source; Human; Humans; Intention to Treat Analysis; Israel; Logistic Models; Logistic Regression; Male; Middle Age; Middle Aged; New Zealand; Odds Ratio; Pain – Diagnosis; Pain – Drug Therapy; Pain – Etiology; Pain – Radiotherapy; Pain Measurement; Pain/diagnosis/drug therapy/*etiology/*radiotherapy; Questionnaires; Radiation; Radiation Dosage; Radiotherapy; Radiotherapy Planning; Risk Factors; Scales; Spinal Cord Compression – Etiology; Spinal Cord Compression/etiology; Spontaneous – Etiology; Spontaneous/etiology; Surveys and Questionnaires; Time Factors; Treatment Outcome; Treatment Outcomes
BACKGROUND: Although repeat radiation treatment has been shown to palliate pain in patients with bone metastases from multiple primary origin sites, data for the best possible dose fractionation schedules are lacking. We aimed to assess two dose fractionation schedules in patients with painful bone metastases needing repeat radiation therapy. METHODS: We did a multicentre, non-blinded, randomised, controlled trial in nine countries worldwide. We enrolled patients 18 years or older who had radiologically confirmed, painful (ie, pain measured as \textgreater/=2 points using the Brief Pain Inventory) bone metastases, had received previous radiation therapy, and were taking a stable dose and schedule of pain-relieving drugs (if prescribed). Patients were randomly assigned (1:1) to receive either 8 Gy in a single fraction or 20 Gy in multiple fractions by a central computer-generated allocation sequence using dynamic minimisation to conceal assignment, stratified by previous radiation fraction schedule, response to initial radiation, and treatment centre. Patients, caregivers, and investigators were not masked to treatment allocation. The primary endpoint was overall pain response at 2 months, which was defined as the sum of complete and partial pain responses to treatment, assessed using both Brief Pain Inventory scores and changes in analgesic consumption. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00080912. FINDINGS: Between Jan 7, 2004, and May 24, 2012, we randomly assigned 425 patients to each treatment group. 19 (4%) patients in the 8 Gy group and 12 (3%) in the 20 Gy group were found to be ineligible after randomisation, and 140 (33%) and 132 (31%) patients, respectively, were not assessable at 2 months and were counted as missing data in the intention-to-treat analysis. In the intention-to-treat population, 118 (28%) patients allocated to 8 Gy treatment and 135 (32%) allocated to 20 Gy treatment had an overall pain response to treatment (p=0.21; response difference of 4.00% [upper limit of the 95% CI 9.2, less than the prespecified non-inferiority margin of 10%]). In the per-protocol population, 116 (45%) of 258 patients and 134 (51%) of 263 patients, respectively, had an overall pain response to treatment (p=0.17; response difference 6.00% [upper limit of the 95% CI 13.2, greater than the prespecified non-inferiority margin of 10%]). The most frequently reported acute radiation-related toxicities at 14 days were lack of appetite (201 [56%] of 358 assessable patients who received 8 Gy vs 229 [66%] of 349 assessable patients who received 20 Gy; p=0.011) and diarrhoea (81 [23%] of 357 vs 108 [31%] of 349; p=0.018). Pathological fractures occurred in 30 (7%) of 425 patients assigned to 8 Gy and 20 (5%) of 425 assigned to 20 Gy (odds ratio [OR] 1.54, 95% CI 0.85-2.75; p=0.15), and spinal cord or cauda equina compressions were reported in seven (2%) of 425 versus two (\textless1%) of 425, respectively (OR 3.54, 95% CI 0.73-17.15; p=0.094). INTERPRETATION: In patients with painful bone metastases requiring repeat radiation therapy, treatment with 8 Gy in a single fraction seems to be non-inferior and less toxic than 20 Gy in multiple fractions; however, as findings were not robust in a per-protocol analysis, trade-offs between efficacy and toxicity might exist. FUNDING: Canadian Cancer Society Research Institute, US National Cancer Institute, Cancer Council Australia, Royal Adelaide Hospital, Dutch Cancer Society, and Assistance Publique-Hopitaux de Paris.
Chow Edward; van der Linden Yvette M; Roos Daniel; Hartsell William F; Hoskin Peter; Wu Jackson S Y; Brundage Michael D; Nabid Abdenour; Tissing-Tan Caroline J A; Oei Bing; Babington Scott; Demas William F; Wilson Carolyn F; Meyer Ralph M; Chen Bingshu E; Wong Rebecca K S
The Lancet. Oncology
2014
2014-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/S1470-2045(13)70556-4" target="_blank" rel="noreferrer noopener">10.1016/S1470-2045(13)70556-4</a>
From mechanisms to management: translating the neuropathic pain consensus recommendations into clinical practice.
Adult; Female; Humans; Middle Aged; Aged; Chronic Disease; Inflammation; Risk Factors; Evidence-Based Medicine; Practice Guidelines as Topic; Patient Selection; Acute Disease; Analgesics/therapeutic use; Patient Education as Topic; *Pain/diagnosis/etiology/physiopathology; Anticonvulsants/therapeutic use; Nervous System Diseases/*complications; Nurse Practitioners; Pain Management; Anesthetics; Drug Therapy; Combination; Antidepressive Agents; Local/therapeutic use; Tricyclic/therapeutic use
Chronic neuropathic pain poses a treatment challenge, and is associated with significant psychologic distress, physical disability, and impaired functioning, which impact the activities of daily living. Efforts to provide relief are often inadequate and/or require polypharmacy. This has spurred interest among researchers and clinicians alike to develop early, intensive treatments that target the molecular and cellular mechanisms involved in pain transduction, transmission, and modulation, or ideally, that prevent neuropathic pain from occurring in the first place. Currently, researchers are attempting to capitalize on our understanding of neuropathic pain pathophysiology to develop drugs that interrupt distinct activities involved in its perpetuation. In this regard, several potential agents (eg, NMDA and AMPA/kainate antagonists) are in phase 2 and 3 clinical trials. In the interim, evolving data and evidence-based neuropathic treatment recommendations provide guidance for selecting first- and second-line medications that alone or in combination offer acceptable neuropathic pain control and allow clinicians to bridge the gap between current knowledge and its application in the clinical setting. Hopefully, as basic and clinical science progresses, further treatment advances and management tools will be found to improve the care of patients who live with neuropathic pain.
Chevlen Eric; Davis Pamela Stitzlein; Rhiner Michelle
Journal of the American Academy of Nurse Practitioners
2005
2005-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Behavioral factors in the management of back pain.
Humans; Physician-Patient Relations; Personality; Analgesics/therapeutic use; *Behavior; Back Pain/diagnosis/*psychology/*therapy; Depression/psychology; Neurotic Disorders/psychology/therapy; Psychotropic Drugs/therapeutic use
Most persons with acute back problems recover promptly. Comprehensive evaluation of those who have not significantly improved within two weeks will often reveal significant behavioral factors that may be impeding recovery. These factors may include interpersonal, economic or occupational stress; psychologic disorders, including anxiety, depression or somatization, and counterproductive beliefs about back disorders. Effective management strategies include building a constructive doctor-patient relationship, addressing life stress issues, keeping patients physically active and prescribing psychotropic and/or analgesic medication when appropriate.
Gillette R D
American Family Physician
1996
1996-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).