Radiotherapy For Painful Bone Metastases Research Articles

Pain response in single-fraction 8-Gy radiotherapy for painful non-bone-metastasis tumors: a single-center retrospective study.

The effectiveness of single-fraction 8-Gy radiotherapy for painful bone metastases has been verified in numerous randomized controlled trials. However, few reports have described the effectiveness of single-fraction 8-Gy radiotherapy in painful tumors other than bone metastases. We conducted a retrospective analysis to evaluate the pain response to single-fraction 8-Gy radiotherapy in painful non-bone-metastasis tumors. We included patients who had received single-fraction 8-Gy radiotherapy for such tumors between January 2017 and December 2022, excluding those with brain metastases, hematological tumors and those who received re-irradiation. Pain response assessment was based on the best responses documented in the medical records and conducted by two radiation oncologists. A total of 36 eligible patients were included in this study. The irradiation sites included primary lesions in eight patients, lymph node metastases in eight, muscle metastases in seven, pleural dissemination in four, skin/subcutaneous metastases in four and other sites in five. Pain response was assessed in 24 patients after radiotherapy. Pain response rate was 88% in evaluable patients; 21 of the 24 patients experienced response. The median assessment date for pain response was 37days (range: 8-156days) after radiotherapy. Re-irradiation was performed in four patients (11%). Single-fraction 8-Gy radiotherapy seemed to be a promising treatment option for painful non-bone-metastasis tumors and warrants further investigation.

Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases

Conventional external beam radiotherapy (cEBRT) and stereotactic body radiotherapy (SBRT) are commonly used treatment options for relieving metastatic bone pain. The effectiveness of SBRT compared with cEBRT in pain relief has been a subject of debate, and conflicting results have been reported. To compare the effectiveness associated with SBRT vs cEBRT for relieving metastatic bone pain. A structured search was performed in the PubMed, Embase, and Cochrane databases on June 5, 2023. Additionally, results were added from a new randomized clinical trial (RCT) and additional unpublished data from an already published RCT. Comparative studies reporting pain response after SBRT vs cEBRT in patients with painful bone metastases. Two independent reviewers extracted data from eligible studies. Data were extracted for the intention-to-treat (ITT) and per-protocol (PP) populations. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Overall and complete pain response at 1, 3, and 6 months after radiotherapy, according to the study's definition. Relative risk ratios (RRs) with 95% CIs were calculated for each study. A random-effects model using a restricted maximum likelihood estimator was applied for meta-analysis. There were 18 studies with 1685 patients included in the systematic review and 8 RCTs with 1090 patients were included in the meta-analysis. In 7 RCTs, overall pain response was defined according to the International Consensus on Palliative Radiotherapy Endpoints in clinical trials (ICPRE). The complete pain response was reported in 6 RCTs, all defined according to the ICPRE. The ITT meta-analyses showed that the overall pain response rates did not differ between cEBRT and SBRT at 1 (RR, 1.14; 95% CI, 0.99-1.30), 3 (RR, 1.19; 95% CI, 0.96-1.47), or 6 (RR, 1.22; 95% CI, 0.96-1.54) months. However, SBRT was associated with a higher complete pain response at 1 (RR, 1.43; 95% CI, 1.02-2.01), 3 (RR, 1.80; 95% CI, 1.16-2.78), and 6 (RR, 2.47; 95% CI, 1.24-4.91) months after radiotherapy. The PP meta-analyses showed comparable results. In this systematic review and meta-analysis, patients with painful bone metastases experienced similar overall pain response after SBRT compared with cEBRT. More patients had complete pain alleviation after SBRT, suggesting that selected subgroups will benefit from SBRT.

A critical appraisal of the four systematic reviews and meta-analysis on stereotactic body radiation therapy versus external beam radiotherapy for painful bone metastases and where we go from here.

Radiotherapy is an important treatment modality for pain control in patients with bone metastases. Stereotactic body radiation therapy (SBRT), which allows delivering a much higher dose per fraction while sparing critical structures compared to conventional external beam radiotherapy (cEBRT), has become more widely used, especially in the oligometastatic setting. Randomized controlled trials (RCTs) comparing the pain response rate of SBRT and cEBRT for bone metastases have shown conflicting results, as have four recent systematic reviews with meta-analyses of these trials. Possible reasons for the different outcomes between these reviews include differences in methodology, which trials were included, and the endpoints examined and how they were defined. We suggest ways to improve analysis of these RCTs, particularly performing an individual patient-level meta-analysis since the trials included heterogeneous populations. The results of such studies will help guide future investigations needed to validate patient selection criteria, optimize SBRT dose schedules, include additional endpoints (such as the time to onset of pain response, durability of pain response, quality of life (QOL), and side effects of SBRT), and better assess the cost-effectiveness and trade-offs of SBRT compared to cEBRT. An international Delphi consensus to guide selection of optimal candidates for SBRT is warranted before more prospective data is available.

Prompt Pain Relief: Advanced Practice Provider Led Rapid Access Palliative Radiotherapy Clinic

Patients (pts) commonly present to radiation oncology with painful bone metastases requiring urgent palliative radiotherapy (RT). Unfortunately, the pre-existing scheduling workflow for palliative referrals can be inefficient, causing significant delays before pts are seen by a radiation oncologist (RO). Our institution implemented an alternative workflow, which led to the creation of an advanced practice provider (APP) led Rapid Access Palliative RT Clinic (PRC). We investigated the impact of the PRC in reducing time from referral to consultation for pts in need of palliative RT. In March 2022, we initiated an outpatient APP led PRC focused on the APP driving consultations supervised by the weekly on-call RO. Pts are offered a variety of options for consultation such as virtual, in clinic with reserved simulation time, and when appropriate virtual simulation, using diagnostic imaging for RT planning, and same day treatment requiring only one visit to the department. The clinic provides a point of contact that fosters multidisciplinary interaction and proactive continuity of care and follow up. Following institutional review board approval, pts who received palliative RT for painful bone metastases from June 2021 to December 2022 were retrospectively reviewed. Data was collected with respect to when the referral was placed for palliative RT and when the pts was seen for consultation by a provider. The cohort of pts seen between June 2022 and December 2022 represented the PRC cohort. A comparison cohort of pts treated between June 2021 and December 2021 represented the pre-PRC cohort. Unpaired T-test was used to analyze time from referral to consultation (TTC) between groups. P value < 0.05 was considered statistically significant. During the pre-PRC period, 91 patients were treated, including 12 inpatients and 79 outpatients, while during the PRC period, 101 pts were treated, including 7 inpatients and 94 outpatients. The median dose was 8 Gy in 1 fraction for both cohorts. During the PRC period, there was a 19% increase in outpatients treated for bone metastases. Restricted to just outpatients, the average TTC was 10.4 days (SD 10.2) for pre-PRC cohort versus 6.3 days (SD 6.6) for the PRC cohort, which was statistically significant (p = 0.003). This was a 39% reduction in TTC. During the PRC period, 17 pts were not seen in the APP led PRC while 77 were seen in the PRC. The most common reason was an erroneous referral for curative intent treatment instead of palliative bone treatment. During the PRC period, those pts seen in the APP led PRC had an average TTC of 5.1 days (SD 4.6) versus 11.5 days (SD 10.64) for those not seen in the PRC (p = 0.03) with a 56% reduction in TTC. The APP led PRC clinic significantly decreased time from referral to consultation for pts requiring urgent palliative RT for painful bone metastases. Further research is underway to determine if the PRC increases referrals, patients treated, patient satisfaction, and the impact on staffing RO.

Prompt Pain Relief from Bone Metastases: Mature Results from the Virtual Simulation Program

Rapidpain relief for patients with bone metastases can be a challenge due to the lengthy and complex radiotherapy workflow. The purpose of this study was to evaluate the time (in days) between initial radiation oncology consultation and start of palliative radiation treatment after implementing an alternative virtual simulation palliative workflow. Patients meeting strict criteria were selected for virtual simulation, which included only those with painful bone metastases who were recommended palliative radiotherapy using standard AP/PA or opposed lateral fields. A recent (within 30 days) diagnostic CT scan clearly visualizing the target volume was required for treatment planning. For comparison, a reference group of 40 consecutive patients with bone metastases that underwent in-person CT simulation prior to virtual simulation implementation was reviewed. Forty-five patients were treated for painful bone metastases as part of the virtual simulation program from May 2021 to October 2022. Regarding travel distance, 23 patients lived locally (<50 miles from treatment center) and 22 patients were distant (≥50 miles from treatment center). Average time from consult to treatment for all virtual simulation patients was 3.7 days compared to 7.5 days for in-person CT simulation patients (3.8 days sooner on average, p = <0.001). For outpatient treatments, average time from consult to treatment for distant virtual simulation patients was 4.0 days compared to 8.9 days for distant in-person CT simulation patients (4.9 days sooner on average, p = 0.003). The virtual simulation program decreased the time from consult to start of treatment for patients recommended palliative radiotherapy for painful bone metastases by over 50%. This benefit was most significant for outpatients traveling ≥ 50 miles for treatment. Virtual simulation-based planning can be considered for patients anxious to proceed with radiotherapy quickly, or in underserved settings with limited transportation options to regional treatment centers.

Treatment outcomes of radiotherapy for malignant psoas syndrome: A single-center retrospective study

IntroductionThe efficacy of radiotherapy for symptomatic relief of malignant psoas syndrome (MPS) remains unknown because there are limited publications with high level evidence, including analyses with sufficient number of cases, clinical trials, and systematic reviews about radiotherapy for MPS. We aimed to investigate the characteristics of and symptom relief rates in patients treated with radiotherapy for MPS in palliative intent. MethodsIn this single-center retrospective study, we analyzed data of 22 consecutive patients treated with radiotherapy for MPS at our institution in Japan between 2012 and 2022. We recorded patient characteristics, including primary site, invasion pattern, recognition of MPS by the attending physician, radiation regimen, biological effective dose with α/β = 10 Gy (BED10), and adverse events. Since no objective evaluation index for palliative radiotherapy for non-bone metastases has been established, we modified and used an International Consensus on Palliative Radiotherapy Endpoint, which was originally used for bone metastases, to evaluate symptom relief in the present retrospective study. “Response” was defined as symptom relief described in medical records or the use of analgesic medications reduced by ≥25% within 3 months post-initiation of radiotherapy. ResultsGenitourinary organs (41%) were the most common primary-tumor sites. MPS was caused by metastasis in the iliopsoas muscle in 14 patients (64%) and by direct invasion of the primary tumor in eight patients (36%). Since the optimal radiation dose for MPS has not been established, the radiation dose varied from low dose, which are used in palliative radiotherapy for painful bone metastases, to high dose with conventional fraction using 1.8 to 2 Gy per fraction, with a median BED10 of 48 Gy (range, 10.6–79.2 Gy). Fifteen patients (68%) achieved a response. No acute nor late adverse events of grade 2 or higher, according to Common Terminology Criteria for Adverse Events version 5.0, were reported during the observation period. ConclusionRadiotherapy for symptomatic MPS might be an effective treatment option with a high response rate (68%) and minimal adverse events. Since the present study is a retrospective study with small number of cases, a prospective study with a larger sample size is required.

Comparison of twice weekly palliative RT versus continuous hypofractionated palliative RT for painful bone metastases.

Palliative hypofractionated radiotherapy (RT) is an effective mode of treating painful bone metastasis. While 8 Gy single fraction radiation is often effective for the same, for complicated bone metastases a protracted fractionated regimen is preferred, of which 30 Gy/10#/2weeks or 20 Gy/5#/1 week are the most common worldwide. However such schedules add to the burden of already overburdened radiation treatment facilities in a busy center, wherein alternative logistic favourable schedules with treatment on weekends are preferred. Here we compare the efficacy of a twice weekly schedule to that of standard continuous 20 Gy/5 #/1 week schedule in terms of pain relief, response and quality of life. A prospective non randomized study was undertaken from Jan 2018 to May 2019, wherein eligible patients of complicated bone metastases received palliative radiotherapy of 20 Gy/5#, either continuously for 5 fractions from Monday to Saturday or twice weekly, Saturday and Wednesday, starting on a Saturday over about 2 weeks. Pain relief was assessed by the Visual Analogue Scale (VAS) and FACES pain scale recorded prior to starting palliative RT and at 4 weeks, 3 months and 6 months. Thirteen patients received continuous Hypofractionated RT while 16 received it in a twice weekly schedule. Spine was the most common site receiving palliative Radiation (27/29), while breast cancer was the most common primary (16/29). The demographic and the baseline characteristics were comparable. The mean pain score decline at 4 weeks was 2.56 ± 1.1 and 2.71 ± 0.52 in the 5-day and the two-week schedule, respectively (p = 0.67). A twice weekly schedule over about two weeks was found to be equivalent in pain control and response to the standard fractionated palliative radiation and, thus, can be safely employed in resource constrained, busy radiotherapy centers.

Randomized controlled study of pain education in patients receiving radiotherapy for painful bone metastases

BackgroundAlthough short-course radiotherapy is an effective treatment for patients with painful bone metastases, pain is not always sufficiently controlled. We therefore investigated the additional effect of a nurse-led pain education program on pain control and quality of life (QoL). Patients and methodsIn this multicenter study, patients with solid tumor bone metastases and a worst pain intensity of ≥5 on a 0–10 numeric rating scale (NRS) were randomized between care as usual (control-group) and care as usual plus the Pain Education Program (PEP-group). PEP consisted of a structured interview and personalized education with follow-up phone calls. Patients completed the Brief Pain Inventory, EORTC QLQ-C15-PAL and BM22 at week 0, 1, 4, 8 and 12. The primary outcome was pain control, defined as the number of patients whose worst pain intensity was <5 on a 0–10 NRS after 12 weeks. Secondary outcomes were time to reach control of pain (NRS < 5), mean worst pain and average pain, and QoL at weeks 1, 4, 8 and 12. ResultsOf 308 included patients, 182 (92 PEP-group) completed 12 weeks follow-up. At 12 weeks, more patients in the PEP-group (71%) compared to the control-group (52%) reported pain control (P =.008). In the PEP-group, pain control was reached earlier than in the control-group (median 29 days versus 56 days; P =.003). Mean worst and average pain decreased in both groups but decreased more in the PEP-group. QoL did not differ between the groups. ConclusionThe addition of PEP to care as usual for patients treated with radiotherapy for painful bone metastases resulted in less pain and faster pain control.

Preliminary Study on Establishing a Heart Rate Variability-based Method for Objectively Evaluating Bone Metastasis Pain.

The aim of this study was to establish an objective evaluation method for pain due to bone metastasis, based on heart rate variability (HRV). In this prospective study, patients who underwent radiotherapy for painful bone metastases were enrolled. Pain was assessed using a numerical rating scale (NRS), and anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). Autonomic and physical activities were evaluated by measuring HRV using a wearable device. NRS, HADS, and R-R interval (RRI) values were obtained upon starting, completing, and 3-5 weeks after radiotherapy. Between July 2020 and July 2021, 11 patients were enrolled. The median average NRS score was 5 (range=2-10). HADS-assessed median anxiety and depression scores were 8 (range=1-13 and 2-21). For patients with an NRS score ≥4, NRS score was significantly associated with low-frequency/high-frequency (LF/HF) component ratio (p=0.03). Heart rate during physical activity was significantly higher than resting heart rate; however, mean resting LF/HF was significantly higher than LF/HF during physical activity. During rest, excluding patients with a HADS depression score ≥7 in an NRS score 1-3, there was a trend for a positive correlation between the NRS score and the mean LF/HF (p=0.07). HRV measurements can objectively evaluate pain due to bone metastasis. However, we must consider that the effects of mental status, such as depression, on LF/HF also affect HRV in patients with cancer with mild pain.

Pain Response Rates after Conventional Radiation Therapy for Bone Metastases Assessed Using International Consensus Pain Response Endpoints: A Systematic Review and Meta-Analysis of Initial Radiation Therapy and Re-Irradiation

<h3>Purpose/Objective(s)</h3> Previous systematic reviews of conventional radiation therapy (RT) for painful bone metastases showed response rates of 72%<b>–</b>75% for initial RT and 68% for re-irradiation. However, the definition of pain response differed among studies included in these reviews. The International Consensus Pain Response Endpoints (ICPRE) was published in 2002 and revised in 2012 to unify evaluation methods for pain response internationally and has been used in many studies. We conducted a systematic review and meta-analysis to determine the pain response rates assessed by ICPRE for both initial RT and re-irradiation. <h3>Materials/Methods</h3> A literature search was conducted in PubMed and Scopus for articles published between 2002 and 2021. The inclusion criteria were as follows: (i) the study designs of randomized controlled trials (RCTs), prospective studies, or studies based on prospectively collected data; and (ii) studies in which pain response was assessed using ICPRE. Our primary outcomes of interest were overall response (OR) rates (sum of complete response rate and partial response rate) for both initial RT and re-irradiation. The following subgroup analyses were performed for OR rates of initial RT: RCT vs. non-randomized studies, with vs. without exclusion criteria for complicated bone metastases, with vs. without eligibility criteria for no change in analgesic use at enrollment, and timing of response assessment (≤1 month vs. >1 month). Random effects logistic models were used to estimate pooled response rates. <h3>Results</h3> Of the 6470 articles identified in our database search, 32 and 3 met the inclusion criteria for analysis of initial RT and re-irradiation, respectively. The OR rates of initial RT in evaluable patients (n = 4775) and intent-to-treat patients (n = 6775) were 60.4% (95% confidence interval [CI], 55.2–65.4) and 45.4% (95% CI, 38.7–52.4), respectively. The OR rates of re-irradiation in evaluable patients (n = 733) and intent-to-treat patients (n = 1085) were 70.8% (95% CI, 15.7–96.9) and 62.2% (95% CI, 5.3–98.0), respectively. Subgroup analyses of initial RT showed no significant differences in any of the comparisons, indicating similar response rates across different study designs. <h3>Conclusion</h3> We determined the pain response rates of initial RT for painful bone metastases assessed by ICPRE. The OR rate assessed by ICPRE was lower than previously reported. The present review may provide benchmarks for future RCTs and non-randomized studies. Regarding the response rate for re-irradiation, the wide range of the 95% CI warrants that the OR rate based on ICPRE requires further investigation.

Preliminary Study on Establishing a Heart Rate Variability–Based Method for Objectively Evaluating Bone Metastasis Pain

<h3>Purpose/Objective(s)</h3> No standardized method objectively evaluates cancer pain. In this case, measuring heart rate variability (HRV) using fluctuations in heartbeat interval (statistical software) may be useful because pain activates sympathetic nerve activity. Fluctuation analysis of RRI frequency demonstrates a high frequency (HF) and low frequency (LF) component. HF represents parasympathetic nerve activity, while the LF-to-HF ratio (LF/HF) represents sympathetic nerve activity. We hypothesized that HRV measurement is an effective and objective evaluation tool for bone metastases pain. <h3>Materials/Methods</h3> This prospective study enrolled patients receiving radiotherapy for painful bone metastases. Pain was assessed using a numerical rating scale (NRS), and anxiety and depression were evaluated based on Hospital Anxiety and Depression Scale (HADS). The average, maximum, and minimum NRS scores were separately evaluated. Autonomic and physical activities were evaluated by measuring HRV through a wearable device (Union Tool Co., Tokyo, Japan). Through a three-dimensional conformal technique, radiotherapy was delivered as 20–30 Gy doses in 5–10 fractions. Alternatively, stereotactic body radiotherapy (SBRT) was delivered as doses of 24 Gy in two fractions or 35 Gy in five fractions. In principle, the values of NRS, HADS, and RRI were obtained upon starting, completing, and 3–5 weeks after radiotherapy. RRI were obtained over approximately 24 h. <h3>Results</h3> Between July 2020 and July 2021, 11 patients were enrolled. The median age was 65 years (range: 50–83 years). Seven of 11 patients were treated with SBRT. We analyzed 27 NRS scores and heart rate interval measurements and 26 HADS scores. The median, average, maximum, and minimum NRS scores were 5 (range: 2–10), 6 (range: 2–10), and 3 (range: 0–8), respectively. HADS-assessed median anxiety and depression scores were both 8 (ranges: 1–13 and 2–21 respectively), and mean HF and LF/HF values were 0.52 ms² (SD: 1.66 ms²) and 2.45 (SD: 1.20), respectively. For all samples, NRS score had no significant relationship with mean LF/HF or HF (p = 0.66 and p = 0.74, respectively). However, for samples with NRS scores ≥ 4, NRS score had a significant association with LF/HF (p = 0.03). Heart rate during physical activity was significantly higher than the resting heart rate; however, mean resting LF/HF was significantly higher than LF/HF during physical activity. During rest, mean LF/HF was not associated with NRS score across all samples, including those with NRS scores ≥ 4 (p = 0.61 and p = 0.49, respectively). In samples excluding those with NRS scores < 4 and HADS depression scores ≥ 7, NRS score had a weak significant relationship with mean LF/HF (p = 0.07). <h3>Conclusion</h3> HRV measurements could objectively evaluate bone metastases pain. However, the effects of mental status, such as depression, on LF/HF affects HRV in cancer patients with mild pain.

Prompt Pain Relief from Bone Metastases: The Virtual Simulation Program

<h3>Purpose/Objective(s)</h3> Patients commonly present to radiation oncology with painful bone metastases. A major bottleneck in delaying treatment of these patients is scheduling a separate CT simulation appointment. We implemented an alternative radiation planning workflow, which utilized a pre-existing diagnostic CT scan "virtual simulation" in lieu of acquiring an additional CT simulation scan. We hypothesized this would significantly decrease the time interval between initial consultation and treatment start date. <h3>Materials/Methods</h3> Patients meeting strict criteria were selected for virtual simulation. This included only those with painful bone metastases in the thorax/abdomen/pelvis/upper femur who would be treated with palliative intent using standard AP/PA or opposed lateral fields. A recent (within 30 days) diagnostic CT scan clearly visualizing the target volume and surrounding anatomy was required for treatment planning and for daily IGRT treatment purposes. Descriptive statistics were used to analyze time from consultation to start of treatment in virtual versus in-person simulation patients. Before and after the virtual simulation study period, surveys were administered to all stakeholders (physicians, nurses, dosimetrists, physicists, and radiation therapists) to assess staff satisfaction of virtual simulation workflow using a Likert scale. Staff were surveyed on their stress levels, how rushed they felt, and overall level of satisfaction. A 1–5-point scale was used with higher numbers indicating worse outcomes such as increased stress, being more rushed, and less satisfaction. <h3>Results</h3> 24 patients were palliatively treated for painful bone metastases as part of this pilot virtual simulation project from May 2021 to January 2022. Median number of fractions for all courses was one fraction. A reference group of 40 patients palliatively treated with in-person CT simulation from February 2021 to July 2021 was also retrospectively reviewed. Median time from consult to start of treatment for in-person CT simulation patients was 167 hours (6.96 days). In comparison, median time from consult to start of treatment for virtual simulation patients was 71 hours (2.96 days). Median duration of treatment itself was 12 minutes for virtual simulation patients versus 9 minutes for in-person simulation patients. 20 surveys were collected prior to the virtual simulation while 15 surveys were collected after the time period. For virtual versus in-person workflows, staff felt less rushed (2.5 vs. 2.8), less stressed (2.0 vs. 2.5), and more satisfied overall (1.86 vs. 2.76). <h3>Conclusion</h3> The virtual simulation program decreased time from consult to start of treatment for patients requiring urgent palliative radiotherapy for painful bone metastases by 57.5% (6.96 vs. 2.96 days). The alternative virtual workflow did not decrease overall staff satisfaction.

Stereotactic Body Radiotherapy vs. Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

<h3>Purpose/Objective(s)</h3> As the superiority of stereotactic body radiotherapy (SBRT) over conventional external beam radiotherapy (cEBRT) remains controversial for pain palliation, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). <h3>Materials/Methods</h3> A systematic review of literature was conducted in PubMed on January 22, 2022, which included prospective RCTs published to date. The inclusion criteria were as follows: (i) RCT comparing SBRT with cEBRT for bone metastases, and (ii) endpoint including pain response. The primary outcome of interest was the overall pain response (OR) rate of bone metastases at 3 months in intention-to-treat analysis. As a subgroup analysis, the analyses on OR were performed in spinal metastases. Pooling of effect sizes across studies was conducted using random-effects models in a meta-analysis of risk ratios. <h3>Results</h3> After 1,246 articles were screened, seven articles comprising 964 patients (522 and 442 patients in the SBRT and cEBRT arms, respectively) met the inclusion criteria. The OR rates of bone metastases at 3 months were 45% (95% confidence interval [CI], 31–60%) and 36% (95% CI, 25–49%) in the SBRT and cEBRT arms, respectively. These studies showed no significant difference between the two groups (risk ratio = 1.19; 95% CI, 0.93–1.53; p = 0.14). In the four studies included for the calculation of OR rates of spinal metastases at 3 months, the SBRT and cEBRT arms included 390 and 307 patients, respectively. The OR rates were 40% (95% CI, 21–62%) and 35% (95% CI, 26–44%) in the SBRT and cEBRT arms, respectively. There was no significant difference between the two groups (risk ratio = 1.14; 95% CI, 0.71–1.84; p = 0.44). The incidence of adverse effects and outcomes of health-related quality of life were comparable between the two arms. <h3>Conclusion</h3> The superiority of SBRT for bone metastases and spinal metastases over cEBRT for pain palliation was not confirmed in this meta-analysis. Although SBRT is a standard of care, treatment indications should not be blindly expanded.

Inflammatory Markers and Radiotherapy Response in Patients With Painful Bone Metastases.

Inflammation is proposed to influence tumor response in radiotherapy (RT). Clinical studies to investigate the relationship between inflammatory markers and RT response is warranted to understand the variable RT efficacy in patients with painful bone metastases. To evaluate the association between inflammatory markers and analgesic response to RT in patients with painful bone metastases. Adult patients from 7 European study sites undergoing RT for painful bone metastases were included in this prospective and longitudinal analysis. The association between RT response and 17 inflammatory markers at baseline, as well as the association between RT response and the changes observed in inflammatory markers between baseline and three and eight weeks after RT, was analyzed with univariate regression analyses. Baseline analyses were adjusted for potential clinical predictors of RT response. None of the inflammatory markers were significantly associated with an upcoming RT response in the analysis of 448 patients with complete baseline data. In patients available for follow-up, the three-week change in TNF (P 0.017), IL-8 (P 0.028), IP-10 (P 0.032), eotaxin (P 0.043), G-CSF (P 0.033) and MCP-1 (P 0.002) were positively associated with RT response, while the three-week change in CRP (P 0.006) was negatively associated. Results from this study show an association between RT response and change in pro-inflammatory mediators and indicate that inflammation may be important to achieve an analgesic RT response in patients with painful bone metastases. None of the investigated inflammatory markers were found to be pre-treatment predictors of RT response.

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

BackgroundStereotactic body radiotherapy (SBRT) is a promising approach in treating painful bone metastases. However, the superiority of SBRT over conventional external beam radiotherapy (cEBRT) remains controversial. Therefore, this systematic review and meta-analysis of randomised controlled trials was conducted to compare SBRT and cEBRT for the treatment of bone metastases.MethodsA search was conducted using PubMed on January 22, 2022, with the following inclusion criteria: (i) randomised controlled trials comparing SBRT with cEBRT for bone metastases and (ii) endpoint including pain response. Effect sizes across studies were pooled using random-effects models in a meta-analysis of risk ratios.ResultsA total of 1246 articles were screened, with 7 articles comprising 964 patients (522 and 442 patients in the SBRT and cEBRT arms, respectively) meeting the inclusion criteria. The overall pain response (OR) rates of bone metastases at 3 months were 45% and 36% in the SBRT and cEBRT arms, respectively. The present analyses showed no significant difference between the two groups. In four studies included for the calculation of OR rates of spinal metastases at three months, the OR rates were 40% and 35% in the SBRT and cEBRT arms, respectively, with no significant difference between the two groups. The incidence of severe adverse effects and health-related quality of life outcomes were comparable between the two arms.ConclusionsThe superiority of SBRT over cEBRT for pain palliation in bone metastases was not confirmed in this meta-analysis. Although SBRT is a standard of care for bone metastases, patients receiving SBRT should be selected appropriately.

Index and Non-index Pain Endpoints in Radiation Therapy for Painful Tumors: A Secondary Analysis of a Prospective Observational Study

Improving pain interference in daily activities, rather than mere pain reduction, is a desirable endpoint for palliative radiation therapy. The association between pain response and pain interference has been studied almost exclusively in patients with painful bone metastases (PBMs), whereas non-index pain has hardly been explored in palliative radiation therapy. We investigated whether index and non-index pain endpoints are associated with changes in pain interference in patients with PBMs and in those with painful non-bone-metastasis tumors (PNTs). Brief Pain Inventory data collected at baseline and at 2 months post-treatment were used to calculate differences in pain interference scores. The treating radiation oncologists differentiated between index pain caused by the irradiated tumor and ‘non-index pain’, the cause of which was not irradiated. Pain response in terms of the index pain was assessed using the International Consensus Endpoint for bone metastases. Patients were diagnosed with predominance of other pain (POP) if non-index pain of malignant or unknown origin was present and had a greater pain score than the index pain. Of 302 patients, 127 (42%) had PBMs and 175 (58%) had PNTs. The median pain interference score, which is based on the mean of the 7 subscale items, decreased to a greater extent among responders than among nonresponders (PBM group: -3.43 vs. -0.57 [P = .005]; PNT group: -2.43 vs. -0.29 [P < .001]). Moreover, patients without POP experienced a greater reduction in their median pain interference score than did those with POP (PBM group: -2.71 vs. -0.43 [P = .004]; PNT group: -2.00 vs. +1.57 [P = .007]). Jonckheere-Terpstra test showed a significant trend across four pain response categories in patients with PBMs and those with PNTs (P < .001 for both). The index and non-index pain endpoints were positively and negatively associated with improvement in pain interference, respectively. There was no apparent difference between patients with PBMs and PNTs in terms of the associations of these endpoints with pain interference. In the next update of the international consensus on palliative radiation therapy endpoints, it may be worth exploring whether non-index pain endpoints should be utilized in radiation therapy for PBMs and whether the International Consensus Endpoint can be used to assess pain palliation in patients with PNTs.

Inconsistencies in assessment of pain endpoints in radiotherapy for painful tumors: Analysis of original articles in the Green and Red Journals

Background and purposeConsistent assessment of the pain response is essential for adequately comparing treatment efficacy between studies. We studied the assessment of pain endpoints in radiotherapy for painful bone metastases (PBMs) and painful non-bone-metastasis tumors (PNTs). Material and methodsWe performed a literature search in the Green (Radiotherapy and Oncology) and Red (International Journal of Radiation Oncology * Biology * Physics) Journals for full-length original articles published between 2009 and 2018. We only included articles that assessed palliation of tumor-related pain after radiotherapy. The data obtained included the definitions of pain response and assessment of non-index pain (pain other than that related to the irradiated tumors). ResultsAmong the 1812 articles identified using the journals’ search function, 60 were included in the analysis. Thirty percent of the PBM articles and approximately half of the PNT articles did not report on analgesic use. Among the prospective studies, 68% of the articles on PBMs and 10% of the articles on PNTs used the International Consensus Endpoint. The PBM articles published in 2014–2018 utilized the International Consensus Endpoint more frequently than those published in 2009–2013 (p = 0.049). No articles reported information on non-index pain. ConclusionsAfter the initial publication of the International Consensus Endpoint, the frequency of its use appears to have risen in PBM research; however, its use in PNT studies has been considerably limited. The International Consensus Endpoint should be consistently utilized in future studies on radiotherapy for painful tumors. Since none of the journal articles had investigated non-index pain, this issue may also needs to be addressed.

Independent External Validation of a Score Predicting Survival After Radiotherapy for Bone Metastases and Expansion to Patients Treated With Single Fraction Radiotherapy.

BackgroundRecently a prognostic score that predicts 12-month survival in patients treated with fractionated radiotherapy for painful bone metastases has been developed. Fractionated radiotherapy might cause unnecessary burden for patients with limited survival, thus estimation of survival is clinically relevant. The purpose of the present study was independent external validation of the new score and, in addition, its application in patients who received single fraction irradiation, a convenient option currently endorsed in several guidelines.MethodsWe conducted a retrospective analysis of 270 patients, including 24% who had received single fraction irradiation. The three-tiered score was assigned as described in the development study, and included age, performance status and primary tumor type. Additional prognostic factors not studied in the development cohort, such as the Glasgow prognostic score (GPS) and presence of liver metastases, were included in this validation study.ResultsThe three-tiered score was valid in this independent cohort (12-month survival rates were 7%, 30% and 71%, respectively, P = 0.0001). Its performance and validity were also confirmed in the single fraction radiotherapy group. Three additional prognostic factors were significant in the multivariate analysis and may therefore contribute to decision making.ConclusionsIrrespective of fractionation, the score based on age, performance status and primary tumor type provides a readily available estimate of 12-month survival.

A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET)

BackgroundBone metastases represent an important source of morbidity in cancer patients, mostly due to severe pain. Radiotherapy is an established symptomatic treatment for painful bone metastases, however, when conventional techniques are used, the effectiveness is moderate. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, could potentially be more effective and less toxic.MethodsThis is a phase III, randomized-controlled, single-blind, multicenter study evaluating the response rate of antalgic radiotherapy for painful bone metastases and the acute toxicity associated with this treatment. A total of 126 patients will be randomly assigned to receive either the standard schedule of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy or a single fraction of 20.0 Gy delivered through SBRT. Primary endpoint is pain response at the treated site at 1 month after radiotherapy. Secondary endpoints are pain flare at 24–48-72 h after radiotherapy, duration of pain response, re-irradiation need, acute toxicity, late toxicity, quality of life and subsequent serious skeletal events. In a supplementary analysis, patient-compliance for a paper-and-pencil questionnaire will be compared with an electronic mode.DiscussionIf a dose-escalated approach within the context of single fraction stereotactic body radiotherapy could improve the pain response to radiotherapy and minimize acute toxicity, this would have an immediate impact on the quality of life for a large number of patients with advanced cancer. Potential disadvantages of this technique include increased pain flare or a higher incidence of radiation-induced fractures.Trial registrationThe Ethics committee of the GZA Hospitals (B099201732915) approved this study on September 4th 2018. Trial registered on Clinicaltrials.gov (NCT03831243) on February 5th 2019.

Efficacy of 8 Gy Single Fraction Palliative Radiation Therapy in Painful Bone Metastases: A Single Institution Experience.

IntroductionBone metastasis (BM) is a major complication of many solid tumors like breast, prostate, lung and renal cancers. BM leads to serious sequelae of pain, fractures, spinal cord compression and hypercalcemia. Radiotherapy has an established role in relieving pain caused by BM. Worldwide different radiotherapy schedules are being used for BM. The aim of this study is to determine the efficacy of single fraction palliative radiotherapy for painful bone metastases.MethodsBetween April 2014 and April 2017, single fraction radiotherapy was used to treat 73 patients in our institution. They had pathologically proven breast, prostate, lung or renal cancer with radiological evidence of bone metastases. There were 39 males (53%) and 34 females (47%). The median age was 58 years (range 33–87 years). 39% patients (n = 28) had breast cancer, 35% had prostate cancer (n = 26), 23% had lung cancer (n = 17), and 3% had renal cancer (n = 2). On presentation, all the patients had a pain score of more than five on Brief Pain Inventory (BPI).ResultsResponse assessment to pain after three months from single fraction radiotherapy was found to be complete response (CR) in 23% patients (n = 17), partial response (PR) in 38% patients (n = 28), stable disease (SD) in 26% patients (n = 19) and progressive disease (PD) in 12% patients (n = 9). The overall efficacy of treatment was 62%, with CR 23% and PR 38%. Pre-treatment mean pain score was 8.15 compared to 4.68 post-treatment (p < 0.001).ConclusionsSingle fraction palliative radiotherapy of 8 Gy showed significant efficacy in painful bone metastases in our setting and merits further investigation in our population.