Efficacy and safety of stereotactic body radiotherapy for painful bone metastases: Evidence from randomized controlled trials.
Frontiers in oncology
Background:Pain relief is one of the main objectives of radiotherapy for cancer patients with bone metastases. Stereotactic body radiotherapy (SBRT) enables precise delivery of a higher dosage to the target area. Several trials have reported comparisons between SBRT and conventional radiotherapy (cRT) in patients with painful bone metastasis. However, the results of those investigations were inconsistent, and no systematic review or meta-analysis has been done till now. Methods:We systematically searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov up to May 1, 2022 for relevant studies. Patients with painful bone metastasis who received SBRT or cRT were included. The primary outcome was the patients' pain response rate at three months. The secondary outcomes included the rate of pain responders at one month and six months, oral morphine equivalent dose (OMED) use, and any adverse events. STATA software 12.0 was used for the statistical analysis. Results:We collected 533 patients' data from 4 randomized controlled trials (RCTs), there was a significant difference of pain response rate at 3 months between two groups (RR = 1.41, 95% CI: 1.12-1.77, = 0.0%, P = 0.003). However, no significant difference was found in pain response rate at 1 month (RR = 1.19, 95% CI: 0.91-1.54, = 31.5%, P = 0.201) and 6 months (RR = 1.25, 95% CI: 0.93-1.69, = 0.0%, P = 0.140). OMED consumption was not significantly different in patients treated with SBRT compared with control group (WMD = -1.11, 95% CI: -17.51-15.28, = 0.0%, P = 0.894). For safety outcome, no statistical difference was found between SBRT and cRT (RR = 0.72, 95% CI: 0.46-1.14, 20.1%, P = 0.162). Conclusion:This study shows that for painful bone metastases, patients with SBRT experienced better pain relief 3 months after radiation than patients with cRT, and SBRT did not increase the incidence of adverse events. Systematic review registration:https://inplasy.com/inplasy-2022-6-0099/, identifier INPLASY202260099.
10.3389/fonc.2022.979201
Combined radio-immunotherapy: An opportunity to increase the therapeutic ratio of oligometastasis-directed radiotherapy.
Neoplasia (New York, N.Y.)
The utility of radiotherapy as a means of palliating symptoms due to metastatic cancer is well-accepted. A growing body of literature suggests that radiotherapy may play a role beyond palliation in some patients with low-burden metastatic disease. Recent data suggest that oligometastasis-directed radiotherapy may improve progression-free and even overall survival in select patients. Immunotherapy also has a growing role in the management of patients with metastatic cancer and, like radiotherapy, appears to be most effective in the setting of low-volume disease. Thus, the addition of immunotherapy may be a feasible means of increasing the therapeutic ratio of metastasis-directed radiotherapy, particularly among patients with oligometastatic cancer.
10.1016/j.neo.2022.100782
Reliability analysis of the epidural spinal cord compression scale.
Bilsky Mark H,Laufer Ilya,Fourney Daryl R,Groff Michael,Schmidt Meic H,Varga Peter Paul,Vrionis Frank D,Yamada Yoshiya,Gerszten Peter C,Kuklo Timothy R
Journal of neurosurgery. Spine
OBJECTIVE:The evolution of imaging techniques, along with highly effective radiation options has changed the way metastatic epidural tumors are treated. While high-grade epidural spinal cord compression (ESCC) frequently serves as an indication for surgical decompression, no consensus exists in the literature about the precise definition of this term. The advancement of the treatment paradigms in patients with metastatic tumors for the spine requires a clear grading scheme of ESCC. The degree of ESCC often serves as a major determinant in the decision to operate or irradiate. The purpose of this study was to determine the reliability and validity of a 6-point, MR imaging-based grading system for ESCC. METHODS:To determine the reliability of the grading scale, a survey was distributed to 7 spine surgeons who participate in the Spine Oncology Study Group. The MR images of 25 cervical or thoracic spinal tumors were distributed consisting of 1 sagittal image and 3 axial images at the identical level including T1-weighted, T2-weighted, and Gd-enhanced T1-weighted images. The survey was administered 3 times at 2-week intervals. The inter- and intrarater reliability was assessed. RESULTS:The inter- and intrarater reliability ranged from good to excellent when surgeons were asked to rate the degree of spinal cord compression using T2-weighted axial images. The T2-weighted images were superior indicators of ESCC compared with T1-weighted images with and without Gd. CONCLUSIONS:The ESCC scale provides a valid and reliable instrument that may be used to describe the degree of ESCC based on T2-weighted MR images. This scale accounts for recent advances in the treatment of spinal metastases and may be used to provide an ESCC classification scheme for multicenter clinical trial and outcome studies.
10.3171/2010.3.SPINE09459
Surgery insight: current management of epidural spinal cord compression from metastatic spine disease.
Witham Timothy F,Khavkin Yevgeniy A,Gallia Gary L,Wolinsky Jean-Paul,Gokaslan Ziya L
Nature clinical practice. Neurology
Metastatic epidural spinal cord compression (MESCC) is becoming a more common clinically encountered entity as advancing systemic antineoplastic treatment modalities improve survival in cancer patients. Although treatment of MESCC remains a palliative endeavor, emerging surgical techniques, in combination with imaging modalities that detect spinal metastatic disease at an early stage, are resulting in improved outcomes. Here, we review the clinical presentation, diagnostic work-up and management options in the management of MESCC. A treatment paradigm is outlined with emphasis on early circumferential surgical decompression of the spinal cord with concomitant spinal stabilization. Radiation therapy has a clearly defined role in the treatment of patients with MESCC, particularly those with radiation-sensitive tumors in the setting of non-bony spinal cord compression and those with a limited life expectancy. Spinal stereotactic radiosurgery, vertebroplasty, and kyphoplasty, are emerging treatment options that are beginning to be used in selected patients with MESCC.
10.1038/ncpneuro0116
Quality of life in responders after palliative radiation therapy for painful bone metastases using EORTC QLQ-C30 and EORTC QLQ-BM22: results of a Brazilian cohort.
Mendez Lucas C,Raman Srinivas,Wan Bo Angela,da Silva José Luiz Padilha,Moraes Fábio Y,Lima Kennya M L B,Silva Maurício F,Diz Maria Del Pilar Estevez,Chow Edward,Marta Gustavo Nader
Annals of palliative medicine
BACKGROUND:Bone metastases cause pain, suffering and impaired quality of life (QoL). Palliative radiotherapy (RT) and/or chemotherapy are effective methods in controlling pain, reducing analgesics use and improving QoL. This study goal was to investigate the changes in QoL scores among patients who responded to palliative treatment. METHODS:A prospective study evaluating the role of radiation therapy in a public academic hospital in São Paulo-Brazil recorded patients' opioid use, pain score, Portuguese version of QLQ-BM22 and QLQ-C30 before and 2 months after radiotherapy. Analgesic use and pain score were used to calculate international pain response category. Overall response was defined as the sum of complete response (CR) and partial response (PR). CR was defined as pain score of 0 with no increase in analgesic intake whereas PR was defined as pain reduction ≥2 without analgesic increase or analgesic reduction in ≥25% without increase in pain at the treated site. RESULTS:From September 2014 to October 2015, 25 patients with bone metastases responded to RT or chemotherapy (1 CR, 24 PR). There were 8 male and 17 female patients. The median age of the 25 patients was 59 (range, 22 to 80) years old. Patient's primary cancer site was breast [11], prostate [5], lung [2], others [7]. For QLQ-BM 22, the mean scores of 4 categories at baseline were: pain site (PS) 39, pain characteristics (PC) 61, function interference (FI) 49 and psycho-social aspects (PA) 57. At 2 month follow up, the scores were PS 27, PC 37, FI 70 and PA 59. Statistical significant improvement (P<0.05) was seen in PS, PC, FI but not PA. In the QLQ-C30, the scores were not statistically different for all categories, except for pain that demonstrated a 33 point decrease in the median pain score domain (66 to 33). CONCLUSIONS:Responders to RT at 2 months presented improvement in BM22 and C30 pain domains, and also improvement in functional interference domain of the BM22 questionnaire.
10.21037/apm.2017.04.06
Effect of Radiotherapy on Painful Bone Metastases: A Secondary Analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23.
McDonald Rachel,Ding Keyue,Brundage Michael,Meyer Ralph M,Nabid Abdenour,Chabot Pierre,Coulombe Genevieve,Ahmed Shahida,Kuk Joda,Dar A Rashid,Mahmud Aamer,Fairchild Alysa,Wilson Carolyn F,Wu Jackson S Y,Dennis Kristopher,DeAngelis Carlo,Wong Rebecca K S,Zhu Liting,Chan Stephanie,Chow Edward
JAMA oncology
IMPORTANCE:Many studies that found improved quality of life (QOL) after radiotherapy of bone metastases have small sample sizes and do not use specific questionnaires. How soon after radiotherapy one can expect an improvement in QOL is unknown. OBJECTIVE:To investigate QOL at days 10 and 42 after radiotherapy with a bone metastases-specific QOL tool. DESIGN, SETTING, AND PARTICIPANTS:In this secondary analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23, a double-blind randomized clinical trial that investigated dexamethasone for the prophylaxis of pain flare after radiotherapy, patients were accrued from 23 Canadian centers from May 30, 2011, to December 11, 2014, and were followed up for 42 days after treatment. Participants referred for radiotherapy for bone metastases were required to have a pain score at the site(s) of treatment of at least 2 (range, 0-10). INTERVENTIONS:Patients were treated with a single 8-Gy radiotherapy dose for 1 or 2 bone metastases. MAIN OUTCOMES AND MEASURES:Patients reported their worst pain score and analgesic intake at baseline and days 10 and 42 after treatment. Pain response was assessed with International Bone Metastases Consensus Endpoint Definitions. Self-reported QOL was completed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Bone Metastases Module (QLQ-BM22) and the European Organisation for Research and Treatment of Cancer Quality of Life Core 15 Palliative (QLQ-C15-PAL) at the same time points. RESULTS:A total of 298 patients were accrued (median age, 68.8 [range, 32-94] years at day 10 and 68.0 [range, 34-90] years at day 42). A total of 122 patients (40.9%) responded to radiotherapy at day 10 and 116 patients (38.9%) at day 42. At day 10, compared with nonresponders, patients with a pain response had a greater reduction in pain (mean reduction, 17.0 vs 1.8; P = .002) and pain characteristics (mean reduction, 12.8 vs 1.1; P = .002), as well as greater improvements in functional interference (mean increase, 11.6 vs 3.6; P = .01) and psychosocial aspects (mean increase, 1.2 points in responders vs mean decrease of 2.2 points in nonresponders, P = .04). Comparing changes in QOL from baseline to day 42, responders had significantly greater improvements in the physical (mean increase, 6.2 vs -9.0; P < .001), emotional (mean increase, 12.3 vs -5.5; P < .001), and global domains (mean increase, 10.3 vs -4.5; P < .001) of the QLQ-C15-PAL compared with nonresponders. CONCLUSIONS AND RELEVANCE:Forty percent of patients experienced pain reduction and better QOL at day 10 after radiotherapy with further improvements in QOL at day 42 in responders. A single 8-Gy radiotherapy dose for bone metastases should be offered to all patients, even those with poor survival. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01248585.
10.1001/jamaoncol.2016.6770
Multifraction radiotherapy for palliation of painful bone metastases: 20 Gy versus 30 Gy.
Valeriani Maurizio,Scaringi Claudia,Blasi Luciana,Carnevale Alessia,De Sanctis Vitaliana,Bonome Paolo,Bracci Stefano,Marrone Gianluca,Minniti Giuseppe,Enrici Riccardo Maurizi
Tumori
AIMS AND BACKGROUND:To compare 2 multifraction radiotherapy schedules in the palliation of painful bone metastases. METHODS AND STUDY DESIGN:We retrospectively analyzed clinical data of 105 patients with a total of 140 painful bone metastases who were treated with 20 Gy in 5 fractions or 30 Gy in 10 fractions. The primary tumors were breast (30%), lung (28%), and prostate (14%). The main sites of irradiation were spine (n = 79) and sacrum or pelvis (n = 39). Pain was graded by patients according to the pain numeric rating scale just before and 1 month after radiotherapy. Pain progression was defined as an increase ≥2 on pain scale after an initial response. RESULTS:The overall response rate at 1 month was 88.6%. Overall response rate was 89.6% in the 20-Gy arm and 87.3% in the 30-Gy arm (p = 0.669). The rate of complete response was statistically better in patients treated with 30 Gy (p = 0.019). The mean reduction in pain was 3.2 in the 20-Gy group and 3.6 in the 30-Gy group. Pain progression was 6.5% and 1.6%, respectively. The incidence of acute toxicity was statistically significantly higher in the 30-Gy arm (23.8%) than in the 20-Gy arm (2.6%) (p = 0.001). One pathologic fracture of the irradiated bone was observed in the 30-Gy arm. Two lesions, one in each group, were re-irradiated for pain recurrence. Pain progression was found in 6.5% of the irradiated lesions in the 20-Gy arm and in 1.6% in the 30-Gy arm. CONCLUSIONS:In our series, both regimens achieved high rate of pain relief, although the group treated with higher total dose reported better complete response rate. The 30-Gy arm had a significantly higher rate of acute toxicity.
10.5301/tj.5000286
An integrated multidisciplinary algorithm for the management of spinal metastases: an International Spine Oncology Consortium report.
Spratt Daniel E,Beeler Whitney H,de Moraes Fabio Y,Rhines Laurence D,Gemmete Joseph J,Chaudhary Neeraj,Shultz David B,Smith Sean R,Berlin Alejandro,Dahele Max,Slotman Ben J,Younge Kelly C,Bilsky Mark,Park Paul,Szerlip Nicholas J
The Lancet. Oncology
Spinal metastases are becoming increasingly common because patients with metastatic disease are living longer. The close proximity of the spinal cord to the vertebral column limits many conventional therapeutic options that can otherwise be used to treat cancer. In response to this problem, an innovative multidisciplinary approach has been developed for the management of spinal metastases, leveraging the capabilities of image-guided stereotactic radiosurgery, separation surgery, vertebroplasty, and minimally invasive local ablative approaches. In this Review, we discuss the variables that should be considered during the management of these patients and review the role of each discipline and their respective management options to provide optimal care. This work is synthesised into a practical algorithm to aid clinicians in the management of patients with spinal metastasis.
10.1016/S1470-2045(17)30612-5
Early identification and intervention matters: A comprehensive review of current evidence and recommendations for the monitoring of bone health in patients with cancer.
Brodowicz Thomas,Hadji Peyman,Niepel Daniela,Diel Ingo
Cancer treatment reviews
Bone metastases are common in patients with advanced solid tumors, and many individuals experience debilitating skeletal-related events (SREs; e.g. pathologic fracture, hypercalcemia, radiotherapy or surgery to bone, and spinal cord compression). These events substantially affect disease outcomes, including survival and quality of life, and healthcare systems. Plain radiography is the most widely used imaging modality for the detection of bone metastases; skeletal scintigraphy, computed tomography, positron emission tomography and magnetic resonance imaging offer greater sensitivity but their use in routine practice is restricted by high costs and limited availability. Biomarkers of bone turnover may also have a role in the early detection of bone metastases and can provide valuable prognostic information on disease progression. SREs can be delayed or prevented using agents such as the receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, denosumab, and bisphosphonates. Painful bone metastases can be treated with radiofrequency ablation, radiotherapy, or radionuclides such as radium-223 dichloride, which has been shown to delay the onset of SREs in men with castration-resistant prostate cancer. Close monitoring of bone health in patients with advanced cancer may lead to early identification of individuals with bone metastases who could benefit from early intervention to prevent SREs. This review examines current guideline recommendations for assessing and monitoring bone health in patients with advanced cancer, use of biomarkers and treatment of patients with bone metastases. The emerging evidence for the potential survival benefit conferred by early intervention with denosumab and bisphosphonates is also discussed, together with best practice recommendations.
10.1016/j.ctrv.2017.09.008
Randomized Double-Blind Trial of Pregabalin Versus Placebo in Conjunction With Palliative Radiotherapy for Cancer-Induced Bone Pain.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE:Cancer-induced bone pain (CIBP) affects one third of patients with cancer. Radiotherapy remains the gold-standard treatment; however, laboratory and clinical work suggest that pregabalin may be useful in treating CIBP. The aim of this study was to examine pregabalin in patients with CIBP receiving radiotherapy. PATIENTS AND METHODS:A multicenter, double-blind randomized trial of pregabalin versus placebo was conducted. Eligible patients were age ≥ 18 years, had radiologically proven bone metastases, were scheduled to receive radiotherapy, and had pain scores ≥ 4 of 10 (on 0-to-10 numeric rating scale). Before radiotherapy, baseline assessments were completed, followed by random assignment. Doses of pregabalin and placebo were increased over 4 weeks. The primary end point was treatment response, defined as a reduction of ≥ 2 points in worst pain by week 4, accompanied by a stable or reduced opioid dose, compared with baseline. Secondary end points assessed average pain, interference of pain with activity, breakthrough pain, mood, quality of life, and adverse events. RESULTS:A total of 233 patients were randomly assigned: 117 to placebo and 116 to pregabalin. The most common cancers were prostate (n = 88; 38%), breast (n = 77; 33%), and lung (n = 42; 18%). In the pregabalin arm, 45 patients (38.8%) achieved the primary end point, compared with 47 (40.2%) in the placebo arm (adjusted odds ratio, 1.07; 95% CI, 0.63 to 1.81; P = .816). There were no statistically significant differences in average pain, pain interference, or quality of life between arms. There were differences in mood (P = .031) and breakthrough pain duration (P = .037) between arms. Outcomes were compared at 4 weeks. CONCLUSION:Our findings do not support the role of pregabalin in patients with CIBP receiving radiotherapy. The role of pregabalin in CIBP with a clinical neuropathic pain component is unknown.
10.1200/JCO.2015.63.8221
Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases: A Randomized Phase 2 Trial.
Nguyen Quynh-Nhu,Chun Stephen G,Chow Edward,Komaki Ritsuko,Liao Zhongxing,Zacharia Rensi,Szeto Bill K,Welsh James W,Hahn Stephen M,Fuller C David,Moon Bryan S,Bird Justin E,Satcher Robert,Lin Patrick P,Jeter Melenda,O'Reilly Michael S,Lewis Valerae O
JAMA oncology
Importance:Consensus is lacking as to the optimal radiotherapy dose and fractionation schedule for treating bone metastases. Objective:To assess the relative efficacy of high-dose, single-fraction stereotactic body radiotherapy (SBRT) vs standard multifraction radiotherapy (MFRT) for alleviation of pain in patients with mostly nonspine bone metastases. Design, Setting, and Participants:This prospective, randomized, single-institution phase 2 noninferiority trial conducted at a tertiary cancer care center enrolled 160 patients with radiologically confirmed painful bone metastases from September 19, 2014, through June 19, 2018. Patients were randomly assigned in a 1:1 ratio to receive either single-fraction SBRT (12 Gy for ≥4-cm lesions or 16 Gy for <4-cm lesions) or MFRT to 30 Gy in 10 fractions. Main Outcomes and Measures:The primary end point was pain response, defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (≥2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. We hypothesized that SBRT was noninferior to MFRT. Results:In this phase 2 noninferiority trial of 96 men and 64 women (mean [SD] age, 62.4 [10.4] years), 81 patients received SBRT and 79 received MFRT. Among evaluable patients who received treatment per protocol, the single-fraction group had more pain responders than the MFRT group (complete response + partial response) at 2 weeks (34 of 55 [62%] vs 19 of 52 [36%]) (P = .01), 3 months (31 of 43 [72%] vs 17 of 35 [49%]) (P = .03), and 9 months (17 of 22 [77%] vs 12 of 26 [46%]) (P = .03). No differences were found in treatment-related toxic effects or quality-of-life scores after SBRT vs MFRT; local control rates at 1 and 2 years were higher in patients receiving single-fraction SBRT. Conclusions and Relevance:Delivering high-dose, single-fraction SBRT seems to be an effective treatment option for patients with painful bone metastases. Among evaluable patients, SBRT had higher rates of pain response (complete response + partial response) than did MFRT and thus should be considered for patients expected to have relatively long survival. Trial Registration:ClinicalTrials.gov identifier: NCT02163226.
10.1001/jamaoncol.2019.0192
Possible Dose-Response Relationship in Palliative Radiotherapy for Non-bone Painful Lesions.
Saito T,Tomitaka E,Toya R,Oya N
Clinical oncology (Royal College of Radiologists (Great Britain))
AIMS:Total radiation dose does not predict pain response in conventionally fractionated radiotherapy for bone metastases. By contrast, in radiotherapy for solid painful tumours other than bone metastases, it is unknown whether there is a dose-response relationship. We sought to determine whether a higher total radiation dose predicted a higher pain response rate in palliative radiotherapy for non-bone painful lesions. MATERIALS AND METHODS:We carried out a secondary analysis of a prospective observational study. For patients scheduled for radiotherapy for painful tumours, Brief Pain Inventory data were collected at baseline and at 1, 2 and 3 months after the start of radiotherapy. The predictive value of total radiation dose was evaluated using the Fine-Gray model, in which death without a pain response was treated as a competing risk. RESULTS:Of the 203 patients with solid painful tumours, 78 (38%) had non-bone painful lesions. There were no significant differences in pain response rate, the rate of the predominance of non-index pain or reductions in pain interference scores between the patients with non-bone lesions and those with bone metastases. Multivariable analysis showed that total radiation dose was an independent significant predictor of pain response in patients with non-bone painful lesions. This result was not robust to sensitivity analysis with Cox regression analysis. CONCLUSIONS:Higher total radiation dose seemed to be associated with a higher rate of pain response in patients with non-bone painful lesions. However, this finding was not robust to sensitivity analysis. Dose-response relationship should be investigated in clinical trials enrolling patients with these kinds of painful tumour.
10.1016/j.clon.2019.03.042