Purpose: Painful bone metastases hamper quality of life (QoL). The aim of this prespecified secondary analysis of the PRESENT trial was to compare change in global QoL, physical functioning,... Show morePurpose: Painful bone metastases hamper quality of life (QoL). The aim of this prespecified secondary analysis of the PRESENT trial was to compare change in global QoL, physical functioning, emotional functioning, functional interference, and psychosocial aspects after conventional radiation therapy (cRT) versus stereotactic body RT (SBRT).Methods and Materials: A total of 110 patients were enrolled in the phase 2 randomized controlled VERTICAL trial (NCT02364115) following the " trials within cohorts" design and randomized 1:1 to cRT or SBRT. Patient-reported global QoL, physical functioning, emotional functioning, functional interference, and psychosocial aspects were assessed by the European Organization for Research and Treatment of Cancer QoL Questionnaire (QLQ) Core 15 Palliative Care and QLQ Bone Metastases 22 modules. Changes in QoL domains over time were compared between patients treated with cRT and SBRT using intention-to-treat (ITT) and per-protocol (PP) linear mixed model analysis adjusting for baseline scores. Proportions of patients in the cRT versus SBRT arm reporting a clinically relevant change in QoL within 3 months were compared using a x2 test.Results: QoL scores had improved over time and were comparable between groups for all domains in both the ITT and PP analyses, except for functional interference and psychological aspects in the ITT. Functional interference scores had improved more after 12 weeks in the cRT arm than in the SBRT arm (25.5 vs 14.1 points, respectively; effect size [ES] = 0.49, P =.04). Psychosocial aspects scores had improved more after 8 weeks in the cRT arm than in the SBRT arm (12.2 vs 7.3; ES = 0.56, P =.04). No clinically relevant differences between groups at 12 weeks in terms of global QoL, physical functioning, emotional functioning, functional interference, and psychosocial aspects were observed.Conclusions: Palliative RT improves QoL. Both SBRT and cRT have a comparable effect on patient-reported QoL outcomes in patients with painful bone metastases. Functional interference and psychological aspects scores improved more in patients treated with cRT versus patients offered SBRT. (C) 2022 Elsevier Inc. All rights reserved. Show less
Purpose: Pain response after conventional external beam radiation therapy (cRT) in patients with painful bone metastases is observed in 60% to 70% of patients. The aim of the VERTICAL trial was to... Show morePurpose: Pain response after conventional external beam radiation therapy (cRT) in patients with painful bone metastases is observed in 60% to 70% of patients. The aim of the VERTICAL trial was to investigate whether stereotactic body radiation therapy (SBRT) improves pain response.Methods and Materials: This single-center, phase 2, randomized controlled trial was conducted within the PRESENT cohort, which consists of patients referred for radiation therapy of bone metastases to our tertiary center. Cohort participants with painful bone metastases who gave broad informed consent for randomization were randomly assigned to cRT or SBRT. Only patients in the intervention arm received information about the trial and were offered SBRT (1 x 18 Gy, 3 x 10 Gy, or 5 x 7 Gy), which they could accept or refuse. Patients who refused SBRT underwent standard cRT (1 x 8 Gy, 5 x 4 Gy, or 10 x 3 Gy). Patients in the control arm were not informed. Primary endpoint was pain response at 3 months after radiation therapy. Secondary outcomes were pain response at any point within 3 months, mean pain scores, and toxicity. Data were analyzed intention to treat (ITT) and per protocol (PP). This trial was registered with Clinicaltrials.gov, NCT02364115.Results: Between January 29, 2015, and March 20, 2019, 110 patients were randomized. ITT analysis included 44 patients in the cRT arm and 45 patients in the SBRT arm. In the intervention arm, 12 patients (27%) declined SBRT, and 7 patients (16%) were unable to complete the SBRT treatment. In ITT, 14 of 44 patients (32%; 95% confidence interval [CI], 18%-45%) in the control arm and 18 of 45 patients (40%; 95% CI, 26%-54%) in the SBRTarm reported a pain response at 3 months (P = .42). In PP, these proportions were 14 of 44 (32%; 95% CI, 18%-45%) and 12 of 23 patients (46%; 95% CI, 27%-66%), respectively (P = .55). In ITT, a pain response within 3 months was reported by 30 of 44 control patients (82%; 95% CI, 68%-90%) and 38 of 45 patients (84%; 95% CI, 71%-92%) in the SBR Tarm (P = .12). In PP, these proportions were 36 of 44 (82%; 95% CI, 68%-90%) and 26 of 27 patients (96%; 95% CI; 81%-100%), respectively (P = .12). No grade 3 or 4 toxicity was observed in either arm.Conclusions: SBRT did not significantly improve pain response in patients with painful bone metastases. One in 4 patients preferred to undergo cRT over SBRT, and 1 in 5 patients starting SBRT was unable to complete this treatment. Because of this selective dropout, which can be attributed to the character of the intervention, the trial was underpowered to detect the prespecified difference in pain response. (C) 2020 The Author(s). Published by Elsevier Inc. Show less
Spencer, K.L.; Velden, J.M. van der; Wong, E.; Seravalli, E.; Sahgal, A.; Chow, E.; ... ; Linden, Y.M. van der 2019
Background Stereotactic radiotherapy (SBRT) might improve pain and local control in patients with bone metastases compared to conventional radiotherapy, although an overall estimate of these... Show moreBackground Stereotactic radiotherapy (SBRT) might improve pain and local control in patients with bone metastases compared to conventional radiotherapy, although an overall estimate of these outcomes is currently unknown.Methods A systematic review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pubmed, Embase, and Cochrane databases were systematically searched to identify studies reporting pain response and local control among patients with bone metastases from solid-organ tumors who underwent SBRT in 1-6 fractions. All studies prior to April 15, 2017, were included. Study quality was assessed by predefined criteria, and pain response and local control rates were extracted.Results A total of 2619 studies were screened; 57 were included (reporting outcomes for 3995 patients) of which 38 reported pain response and 45 local control rates. Local control rates were high with pain response rates above those previously reported for conventional radiotherapy. Marked heterogeneity in study populations and delivered treatments were identified such that quantitative synthesis was not appropriate. Reported toxicity was limited. Of the pain response studies, 73.7% used a retrospective cohort design and only 10.5% used the international consensus endpoint definitions of pain response. The median survival within the included studies ranged from 8 to 30.4months, suggesting a high risk of selection bias in the included observational studies.Conclusions This review demonstrates the potential benefit of SBRT over conventional palliative radiotherapy in improving pain due to bone metastases. Given the methodological limitations of the published literature, however, large randomized trials are now urgently required to better quantify this benefit. Show less
Velden, J.M. van der; Linden, Y.M. van der; Versteeg, A.L.; Verlaan, J.J.; Sophie Gerlich, A.; Pielkenrood, B.J.; ... ; Verkooijen, H.M. 2018
