Randomized Pilot Study of 20 Gy in 5 Fractions versus 27 Gy in 3 Fractions Radiotherapy for Treating Painful Bone Metastases: A Single Institution Experience

Abstract

Purpose: Radiotherapy is a very effective tool in the treatment of painful bone metastases. The aim of this study was to compare the palliative effect of radiotherapy between the standard fractionation schedule 20 Gy over 5 fractions (20Gy/5fr) and the high biological dose schedule 27 Gy over 3 fractions (27Gy/3fr) which is frequently used in Stereotactic body radio-surgery (SBRT). Methods: Patients were randomized to receive (20Gy/5fr)or (27Gy/3fr). The primary aim of the study was pain relief using the numeric rating scale (NRS), after three months of radiation therapy. Secondary end points include pain relief immediately after finishing radiation therapy (within one week), and narcotic relief after three months of radiation therapy. Results: Twenty-two patients with painful bone metastases were included. 12 patients received (20Gy/5fr) and 10 patients received (27Gy/3fr). Male patients were predominant on both arms (81.8%) with a mean age of 58 years [ranging between 19-72 years]. For pain relief after three months of radiation therapy, partial pain relief was documented in 9 patients (75%) with (20Gy/5fr) and in 8 patients (80%) with (27Gy/3fr) with a p- value of 0.6. Additionally, narcotic relief after three months was equal for both groups. For immediate pain relief, partial pain relief was seen in one patient (8%) with (20Gy/5fr) versus seven patients (70%) with (27Gy/3fr) with a p value of 0.06. The increase in immediate pain relief in the 27Gy arm was numerically but not statistically significant. Conclusion: SBRT and standard fractionation radiation therapy had equal effectiveness for pain relief, when the assessment was done after three months of radiation therapy. Interestingly, SBRT had a better immediate pain relief.

Palliative Efficacy of High-Dose Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Painful Non-Spine Bone Metastases: A Propensity Score-Matched Analysis

“…Although the present study demonstrated the superiority of SBRT for pain palliation, randomized controlled trials comparing the pain-relieving effects between SBRT and cEBRT for bone metastases reported paradoxical results: superiority of SBRT over cEBRT [ 10 , 22 ] and non-superiority [ 23 , 24 , 25 , 26 , 27 ]. Consequently, the superior effectiveness of SBRT is still uncertain.…”

Stereotactic body radiotherapy versus conventional radiotherapy for painful bone metastases: a systematic review and meta-analysis of randomised controlled trials

“…of patients No. of patients with spinal metastases Minimum pain score for entry cEBRT dose (Gy/fx) SBRT dose (Gy/fx) SBRT dose (BED 10 , Gy) Dose gradient inside the PTV in SBRT Partial response definition Complete response definition Nguyen et al [ 15 ] 2019 Phase 2 160 0 2 30/10 12/1, 16/1 26.4, 41.6 PTV Dmax < 115% PD ICPRE criteria ICPRE criteria Berwouts et al [ 16 ] 2015 Phase 2 30 12 2 8/1 16/1 41.6 PTV Dmax ≤ 112.5% PD ICPRE criteria ICPRE criteria Ryu et al [ 10 ] 2019 Phase 3 353 353 5 8/1 16/1, 18/1 41.6, 50.4 No rules Improvement of ≥ 3 points without increasing the analgesic dose ICPRE criteria Sakr et al [ 17 ] 2020 Phase 2 22 Not available 4 20/5 27/3 51.3 Not available ICPRE criteria …”

“…Among the seven trials used for analysis in this study, four were assessed to have a low risk of bias, and one was assessed to have some concerns of bias (Additional file 2 ). Two trials were determined to have a high risk of bias owing to an undescribed randomisation procedure [ 17 ] and deviations from intended interventions [ 18 ].…”

Use and Reporting of Patient-Reported Outcomes in Trials of Palliative Radiotherapy

“…Among the published trials, 116 trials (52%) used PROs. PROs were primary end points in 45 trials 20,26,28,30,[34][35][36][37]42,48,53,[56][57][58][61][62][63]66,70,74,75,77,79,83,85,93,94,97,103,[108][109][110]113,115,117,118,124,125,127,128,130,133,134,137 (20% of all published trials; 31% of 145 trials clearly stating their primary end point; 39% of 116 trials including a PRO) and secondary end points in 71 trials 24,25,27,29,[31][32][33]…”

“…Median (IQR) sample size was 98 (41-230) patients in trials with a PRO as a primary end point, and 50 (31-132) patients in trials with a PRO as a secondary end point. Metastases and thoracic primaries were the most common treated sites (eFigure 3 in the Supplement ), including in 37 published trials 26 , 28 , 30 , 34 , 35 , 36 , 37 , 42 , 48 , 53 , 57 , 61 , 63 , 70 , 74 , 75 , 77 , 79 , 83 , 85 , 93 , 94 , 103 , 108 , 109 , 110 , 113 , 115 , 117 , 118 , 123 , 124 , 125 , 126 , 128 , 133 , 137 (82%) with a PRO as a primary end point and in 50 published trials 27 , 29 , 31 , 32 , 33 , 38 , 39 , 40 , 41 , 43 , 44 , 46 , 51 , 54 , 55 , 65 , 67 , 68 ,…”