Re-treatment of bone metastases for pain control: 2023 ASTRO education panel.

Bone metastases are a common and debilitating consequence of advanced cancer, often necessitating palliative radiation therapy (RT) for pain relief. Reirradiation (reRT) of bone metastases is often considered after lack of pain relief following an initial course of RT, after a partial but unsatisfying pain response to an initial course of radiotherapy, or after pain recurrence following a complete or partial pain response to an initial course of RT. The NCIC CTG SC.20 trial, a landmark multicenter, randomized, non-blinded, controlled non-inferiority trial, addressed the critical question of optimal dose fractionation for reRT in this patient population. This trial compared the efficacy and toxicity of a single 8 Gy fraction to multiple fractions totaling 20 Gy in 850 patients with painful bone metastases requiring reRT. The primary endpoint was overall pain response at 2 months, with secondary endpoints of quality of life (QoL) measures, functional interference, and toxicity profiles assessed using patient-reported questionnaires and the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. The intention-to-treat analysis revealed no significant difference in pain response between the two arms, meeting the pre-specified non-inferiority criteria. The per-protocol analysis suggested a potential benefit for a subset of patients receiving multiple fractions, although this was not statistically robust. Acute toxicities were more prevalent in the multiple fractions arm, with implications for patient comfort and healthcare utilization. Importantly, responders to reRT reported significant improvements in functional interference and QoL. The trial's findings support the use of a patient-centric approach to palliative RT, highlighting the viability of a single 8 Gy fraction as a less toxic and more convenient treatment option, albeit with consideration for individual patient circumstances. These results have significant implications for clinical practice, potentially reducing healthcare burdens while optimizing patient convenience during palliative care for painful bone metastases.

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 37 days (range: 8-156 days) 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.

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND: The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS: Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months.

Assessing the effectiveness of palliative radiotherapy for painful bone metastases in low- and middle-income countries: A systematic review.

Palliative radiotherapy (RT) effectively relieves pain in patients with bone metastases (BMs). Furthermore, several clinical trials, in most cases conducted in high-income countries (HICs), proved that single-fraction RT is equally effective compared to multi-fractionated RT. However, the evidence is scarce regarding low/middle-income countries (LMICs), where the diagnosis of BMs could be later and RT techniques less advanced. Therefore, we conducted a systematic literature review to evaluate the efficacy of palliative RT of BMs in the LMIC setting. A literature search was performed independently by two authors on the PubMed, Cochrane and Scopus databases. Overall, 333 records were screened and after the selection process, 11 papers were included in the analysis. Complete pain response rates ranged from 11.5% to 37.1% (median: 22%) for single-fraction RT and from 0% to 35.1% (median: 19%) for multi-fractionated RT. Partial pain response rates ranged from 23.1% to 76.9% (median: 53.8%) for single fraction RT and from 23.8% to 84.6% (median: 65%) for multi-fractionated RT. Four randomized trials compared single-fraction RT with multiple-fraction RT and none of them showed significant differences in terms of pain relief. Our analysis showed that pain response rates after palliative RT recorded in LMIC are like those reported in studies performed in HIC. Even in this setting, RT in single fraction shows comparable pain response rates to multifractional RT.

Comparative Analysis of Stereotactic Radiation Therapy and Conventional Radiation Therapy in Cancer Pain Control: A Systematic Review and Meta-Analysis.

AIMS: Approximately 55% of patients diagnosed with primary or metastatic cancer endure pain directly attributable to the disease. Consequently, it becomes imperative to address pain management through a comparative analysis of stereotactic radiotherapy (SRT) and conventional radiation therapy (CRT), especially in light of the less efficacious improvement achieved solely through pharmacological interventions. MATERIALS AND METHODS: A systematic exploration was undertaken on PubMed, the Cochrane Library, and Elsevier's ScienceDirect databases to identify studies that compare Stereotactic Radiotherapy to Conventional radiation therapy for pain management in individuals with metastatic bone cancer. The analyses were executed utilizing the random-effects model. RESULTS: A cohort of 1152 participants with metastatic bone cancer was analyzed, demonstrating significantly higher complete pain relief in the Stereotactic Radiotherapy group during both early and late follow-up (RR: 1.61; 95% CI: 1.17, 2.23, p-value: 0.004; I2: 0%). Stereotactic Radiotherapy also showed a non-significant increase in the incidence of partial pain relief (RR: 1.07; 95% CI: 0.85, 1.34, p-value: 0.56; I2: 18%). Furthermore, Stereotactic Radiotherapy was associated with a significantly reduced risk of stationary pain throughout follow-up (RR: 0.61; 95%CI: 0.48, 0.76, p-value: <0.0001; I2: 0. The incidence of progressive pain was non-significantly reduced with Stereotactic Radiotherapy during both early and late follow-up (RR: 0.77; 95% CI: 0.50, 1.17, p-value: 0.22; I2: 0%). Secondary outcomes exhibited a non-significant trend favoring Stereotactic Radiotherapy for dysphagia, esophagitis, pain, and radiodermatitis, while a non-significant increase was observed for nausea, fatigue, and vertebral compression fracture. CONCLUSION: In summary, stereotactic radiation therapy (SRT) has improved in achieving complete pain relief while exhibiting a decreased probability of delivering stationary pain compared to conventional radiation therapy (CRT). Nevertheless, it is crucial in future research to address a noteworthy limitation, specifically, the risk of vertebral compression fracture.

Classification of Patients With Painful Tumors to Predict Response to Palliative Radiation Therapy.

PURPOSE: This study aimed to identify factors affecting pain response to develop a patient classification system for palliative radiation therapy (RT). METHODS AND MATERIALS: Our prospective observational study (UMIN000044984) provided data on patients who received palliative RT for painful tumors. The eligibility criteria were having a numerical rating scale (NRS) score of 2 or more before treatment and receiving palliative RT between August 2021 and September 2022. Post-RT follow-up was scheduled prospectively at 2, 4, 12, 24, 36, and 52 weeks. Pain response was assessed using the International Consensus Pain Response Endpoints criteria, with the primary outcome being the response rate within 12 weeks. Multivariable logistic regression was performed to identify factors affecting pain response and develop the classification system. Each class evaluated the differences in response rate, time to response, and progression. RESULTS: Of the 488 registered lesions, 366 from 261 patients met the criteria. Most patients had bone metastases (75%), of whom 72% were using opioids and 22% underwent reirradiation. Conventional RT (eg, 8-Gy single fraction, 20 Gy in 5 fractions) was administered to 93% of patients. Over a median of 6.8 months of follow-up, the average NRS decreased from 6.1 to 3.4 at 12 weeks for 273 evaluable lesions, with a 60% response rate. Opioid use and reirradiation negatively affected the response rate in multivariate analysis (P < .01). Lesions were categorized into class 1 (no opioid use and no reirradiation; 89 lesions), class 2 (neither class 1 nor 3; 211 lesions), and class 3 (opioid use and reirradiation; 66 lesions), with respective response rates of 75%, 61%, and 36% (P < .001). Time to response was similar across the classes (P = .91), but the progression rates at 24 weeks differed (11%, 27%, and 63%, respectively; P < .001). CONCLUSIONS: Opioid use and reirradiation are factors leading to significant variations in pain response rates and time to progression.

Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis.

Importance: 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. Objective: To compare the effectiveness associated with SBRT vs cEBRT for relieving metastatic bone pain. Data Sources: 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. Study Selection: Comparative studies reporting pain response after SBRT vs cEBRT in patients with painful bone metastases. Data Extraction and Synthesis: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

Palliative radiotherapy for painful non-bone lesions in patients with advanced cancer: a single center retrospective study.

PURPOSE: This retrospective study aimed to assess the efficacy and safety of palliative radiotherapy for painful non-bone lesions in patients with advanced cancer. MATERIALS AND METHODS: We enrolled patients with painful non-bone lesions who underwent conventional palliative radiotherapy between September 2018 and September 2022. The treatment targets included primary tumor lesions, lymph node metastases, non-bone hematogenous metastases, and other lesions. The primary endpoint was the overall pain response rate in evaluable patients, determined based on the International Consensus Pain Response Endpoint criteria. The secondary endpoints included overall survival, pain recurrence, and adverse events. RESULTS: Of the 420 screened patients, 142 received palliative radiotherapy for painful non-bone lesions, and 112 were evaluable. A pain response was achieved in 67 patients (60%) of the 112 evaluable patients within a median of 1.2 months. Among these patients, 25 exhibited complete response, 42 partial response, 18 indeterminate response, and 27 pain progression. The median survival time was 5.5 months, recorded at a median follow-up of 6.0 months, during which 67 patients died. Multivariate analysis identified poor performance status scores of 2-4, opioid use, and re-irradiation as independent factors associated with a reduced likelihood of achieving a pain response. Pain recurrence occurred in 18 patients over a median of 4.1 months. Seventeen patients had grade 1-2 adverse events, while none experienced grade 3 or higher toxicity. CONCLUSION: Palliative radiotherapy can potentially be a safe and well-tolerated modality for managing painful non-bone lesions, with a low rate of adverse events.

Clinical Outcomes After Stereotactic Body Radiation Therapy for Nonspinal Bone Metastases: A Systematic Review and Meta-analysis.

There are limited data available on clinical outcomes after stereotactic body radiation therapy (SBRT) for nonspinal bone metastases. We performed a systematic review and meta-analysis to characterize local control (LC), overall survival (OS), pain response rates, and toxicity after SBRT. The primary outcomes were 1-year LC, incidence of acute and late grade 3 to 5 toxicities, and overall pain response rate at 3 months. The secondary outcome was 1-year OS. The Newcastle-Ottawa scale was used for assessment of study bias, with a median score of 5 for included studies (range, 4-8). Weighted random-effects meta-analyses were conducted to estimate effect sizes. We identified 528 patients with 597 nonspinal bone lesions in 9 studies (1 prospective study and 8 retrospective observational studies) treated with SBRT. The estimated 1-year LC rate was 94.6% (95% CI, 87.0%-99.0%). The estimated 3-month combined partial and complete pain response rate after SBRT was 87.7% (95% CI, 55.1%-100.0%). The estimated combined acute and late grade 3 to 5 toxicity rate was 0.5% (95% CI, 0%-5.0%), with an estimated pathologic fracture rate of 3.1% (95% CI, 0.2%-9.1%). The estimated 1-year OS rate was 71.0% (95% CI, 51.7%-87.0%). SBRT results in excellent LC and palliation of symptoms with minimal related toxicity. Prospective investigations are warranted to further characterize long-term outcomes of SBRT for patients with nonspinal bone metastases.

An Economic Analysis of SC24 in Canada: A Randomized Study of SBRT Compared With Conventional Palliative RT for Spinal Metastases.

PURPOSE: The Canadian Cancer Trials Group (CCTG) Symptom Control 24 protocol (SC.24) was a multicenter randomized controlled phase 2/3 trial conducted in Canada and Australia. Patients with painful spinal metastases were randomized to either 24 Gy/2 stereotactic body radiation therapy (SBRT) or 20 Gy/5 conventional external beam radiation therapy (CRT). The study met its primary endpoint and demonstrated superior complete pain response rates at 3 months following SBRT (35%) versus CRT (14%). SBRT planning and delivery is resource intensive. Given its benefits in SC.24, we performed an economic analysis to determine the incremental cost-effectiveness of SBRT compared with CRT. METHODS AND MATERIALS: The trial recruited 229 patients. Cost-effectiveness was assessed using a Markov model taking into account observed survival, treatments costs, retreatment, and quality of life over the lifetime of the patient. The EORTC-QLU-C10D was used to determine quality of life values. Transition probabilities for outcomes were from available patient data. Health system costs were from the Canadian health care perspective and were based on 2021 Canadian dollars (CAD). The incremental cost-effectiveness ratio (ICER) was expressed as the ratio of incremental cost to quality-adjusted life years (QALY). The impact of parameter uncertainty was investigated using deterministic and probabilistic sensitivity analyses. RESULTS: The base case for SBRT compared with CRT had an ICER of $9,040CAD per QALY gained. Sensitivity analyses demonstrated that the ICER was most sensitive to variations in the utility assigned to "No local failure" ($5,457CAD to $241,051CAD per QALY), adopting low and high estimates of utility and the cost of the SBRT (ICERs ranging from $7345-$123,361CAD per QALY). It was more robust to variations in assumptions around survival and response rate. CONCLUSIONS: SBRT is associated with higher upfront costs than CRT. The ICER shows that, within the Canadian health care system, SBRT with 2 fractions is likely to be more cost-effective than CRT.

Excellent long-term pain response and local control following postoperative radiotherapy in patients with multiple myeloma.

PURPOSE: Multiple myeloma is associated with osteolytic bone lesions, often requiring surgery of the spine and postoperative radiotherapy (RT). Although common, data for clinical and informed decision-making are sparse. In this monocentric retrospective study, we aim to report the outcome of patients who underwent spinal surgery and postoperative RT due to multiple myeloma. METHODS: A total of 54 patients with multiple myeloma who underwent prior spinal surgery and postoperative RT at our institution between 2009 and 2020 were analyzed. Spinal instability neoplastic score (SINS) and Bilsky score, posttherapeutic adverse events, clinical data, and outcomes were collected and analyzed. The primary endpoint of this study was overall survival (OS), secondary endpoints were progression-free survival (PFS), pain response, local control, and skeletal-related events (SRE). RESULTS: The 3­ and 5­year overall survival (OS) was 74.9% (95% confidence interval [CI]: 63.5-88.4%) and 58% (95% CI: 44.5-75.6%), respectively. Median survival was not reached and 75% survival was 34.3 months (95% CI: 28.7-95.4 months). Median follow-up was 63 months (95% CI: 49-94 months). The number of patients with good to adequate performance status (Karnofsky performance score [KPS] ≥ 70) significantly increased after surgery (p < 0.01). We observed no grade 3/4 toxicity and only 13 (24%) grade 1/2 adverse events. Two patients (4%) experienced SRE. Overall, 92% of patients reported reduced pain after radiotherapy, with 66% reporting complete pain response. There was no difference in pain response between patients with different Bilsky scores. Bisphosphonate therapy and lower Bilsky score at the start of RT were associated with improved OS in univariate analysis (all p < 0.05). Multivariate Cox regression confirmed a Bilsky score of 2 or 3 as an independent negative prognostic factor (HR 3.89; 95 CI 1.4-10.7; p < 0.01). We observed no in-field recurrences. CONCLUSION: In this study, we were able to show that the current standard of RT after spinal surgery of osteolytic lesions is safe. In addition, we observed a very low rate of SRE (4%) and no in-field recurrences, demonstrating the local efficacy of RT in multiple myeloma patients. Higher Bilsky scores were associated with worse OS in multivariate analysis, but had no effect on pain response.

Impact of Short-Course Palliative Radiation Therapy on Pancreatic Cancer-Related Pain: Prospective Phase 2 Nonrandomized PAINPANC Trial.

PURPOSE: Clinical evidence is limited regarding palliative radiation therapy for relieving pancreatic cancer-related pain. We prospectively investigated pain response after short-course palliative radiation therapy in patients with moderate-to-severe pancreatic cancer-related pain. METHODS AND MATERIALS: In this prospective phase 2 single center nonrandomized trial, 30 patients with moderate-to-severe pain (5-10, on a 0-10 scale) of pancreatic cancer refractory to pain medication, were treated with a short-course palliative radiation therapy; 24 Gy in 3 weekly fractions (2015-2018). Primary endpoint was defined as a clinically relevant average decrease of ≥2 points in pain severity, compared with baseline, within 7 weeks after the start of treatment. Secondary endpoint was global quality of life (QoL), with a clinically relevant increase of 5 to 10 points (0-100 scale). Pain severity reduction and QoL were assessed 9 times using the Brief Pain Inventory and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C15-PAL, respectively. Both outcomes were analyzed using joint modeling. In addition, acute toxicity based on clinician reporting and overall survival (OS) were assessed. RESULTS: Overall, 29 of 30 patients (96.7%) received palliative radiation therapy. At baseline, the median oral morphine equivalent daily dose was 129.5 mg (range, 20.0-540.0 mg), which decreased to 75.0 mg (range, 15.0-360.0 mg) after radiation (P = .021). Pain decreased on average 3.15 points from baseline to 7 weeks (one-sided P = .045). Patients reported a clinically relevant mean pain severity reduction from 5.9 to 3.8 points (P = .011) during the first 3 weeks, which further decreased to 3.2 until week 11, ending at 3.4 (P = .006) in week 21 after the first radiation therapy fraction. Global QoL significantly improved from 50.5 to 60.8 during the follow-up period (P = .001). Grade 3 acute toxicity occurred in 3 patients and no grade 4 to 5 toxicity was observed. Median OS was 11.8 weeks, with a 13.3% 1-year actuarial OS rate. CONCLUSIONS: Short-course palliative radiation therapy for pancreatic cancer-related pain was associated with rapid, clinically relevant reduction in pain severity, and clinically relevant improvement in global QoL, with mostly mild toxicity.

Focused Ultrasound and RadioTHERapy for non-invasive palliative pain treatment in patients with bone metastasis: a study protocol for the three armed randomized controlled FURTHER trial.

BACKGROUND: Cancer-induced bone pain (CIBP), caused by bone metastases, is a common complication of cancer and strongly impairs quality of life (QoL). External beam radiotherapy (EBRT) is the current standard of care for treatment of CIBP. However, approximately 45% of patients have no adequate pain response after EBRT. Magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) may improve pain palliation in this patient population. The main objective of this trial was to compare MR-HIFU, EBRT, and MR-HIFU + EBRT for the palliative treatment of bone metastases. METHODS/DESIGN: The FURTHER trial is an international multicenter, three-armed randomized controlled trial. A total of 216 patients with painful bone metastases will be randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or combined treatment with EBRT followed by MR-HIFU. During a follow-up period of 6 months, patients will be contacted at eight time points to retrieve information about their level of pain, QoL, and the occurrence of (serious) adverse events. The primary outcome of the trial is pain response at 14 days after start of treatment. Secondary outcomes include pain response at 14 days after trial enrolment, pain scores (daily until the 21st day and at 4, 6, 12 and 24 weeks), toxicity, adverse events, QoL, and survival. Cost-effectiveness and cost-utility analysis will be conducted. DISCUSSION: The FURTHER trial aims to evaluate the effectiveness and cost-effectiveness of MR-HIFU-alone or in combination with EBRT-compared to EBRT to relieve CIBP. The trial will be performed in six hospitals in four European countries, all of which are partners in the FURTHER consortium. TRIAL REGISTRATION: The FURTHER trial is registered under the Netherlands Trials Register number NL71303.041.19 and ClinicalTrials.gov registration number NCT04307914. Date of trial registration is 13-01-2020.

Single-Fraction Celiac Plexus Radiosurgery: A Preliminary Proof-of-Concept Phase 2 Clinical Trial.

BACKGROUND: Refractory epigastric/midback pain is associated with locally advanced abdominal malignancies, especially pancreatic cancer. The pain is caused by tumor infiltration of the celiac plexus, a nerve network attached to the abdominal aorta. Contemporary palliative approaches are often inadequate. We hypothesized that ablative radiation targeted to the celiac plexus would alleviate this pain. METHODS AND MATERIALS: We performed a single-arm prospective clinical trial (ClinicalTrials.gov identifier: NCT02356406). Eligible and evaluable patients had celiac pain of at least 5 out of 10 on the Numerical Rating Scale, completed treatment per protocol, and had at least 1 posttreatment visit. The entire retroperitoneal celiac plexus was irradiated with a single 25-Gy fraction. The primary endpoint was change in the Numerical Rating Scale 3 weeks posttreatment. Toxic effects and pain interference (as measured with the Brief Pain Inventory) were secondary endpoints. RESULTS: For our study, 31 patients signed consent, and, of these, 18 patients were treated and evaluable. Median age was 68 years (range, 51-79); 89% of the patients had pancreatic cancer; the median Eastern Cooperative Oncology Group performance status was 1; and the median interval from initial diagnosis to treatment was 9 months (range, 1-36), and, in this interval, patients received a median of 1 systemic treatment line (range, 0-3). Acute toxicity was limited to grade 1 to 2. Three weeks after treatment, 16 patients (84%) reported decreased celiac pain, with median pain level falling from 6 out of 10 (interquartile range [IQR], 5.0-7.5) at baseline to 3 out of 10 (IQR, 1.0-4.3); six weeks after treatment, the Numerical Rating Scale number fell further to 2.8 out of 10 (IQR, 0-3.3; both P < .005 vs baseline), including 4 patients who reported complete eradication of their celiac pain. Total daily morphine milligram equivalents decreased from 59 pretreatment to 50 at 3 weeks, and from 50 to 45 at 6 weeks. Significant improvement was seen in pain-interference scores. CONCLUSIONS: Celiac plexus radiosurgery appears to alleviate cancer-related pain. An international multicenter phase 2 trial is currently accruing.

MR-guided adaptive stereotactic body radiotherapy (SBRT) of primary tumor for pain control in metastatic pancreatic ductal adenocarcinoma (mPDAC): an open randomized, multicentric, parallel group clinical trial (MASPAC).

BACKGROUND: Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial. METHODS: This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the "mean cumulative pain index" rated every 4 weeks until death or end of study using numeric rating scale. DISCUSSION: An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life. TRIAL REGISTRATION: German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213.

Radiotherapy of bone metastases.

We present the update of the recommendations of the French society of oncological radiotherapy on bone metastases. This is a common treatment in the management of patients with cancer. It is a relatively simple treatment with proven efficacy in reducing pain or managing spinal cord compression. More complex treatments by stereotaxis can be proposed for oligometastatic patients or in case of reirradiation. In this context, increased vigilance should be given to the risks to the spinal cord.

Single-center outcomes of image-guided radiotherapy in the management of vertebral hemangioma with daily kilovoltage cone-beam computerized tomography.

BACKGROUND: Vertebral hemangiomas are defined as benign proliferation of blood vessels. Vertebral hemangiomas are generally found incidentally by computerized tomography or magnetic resonance imaging; however, they may also cause pain and quality-of-life impairment in some circumstances with reference to their location and association with the spinal cord. In this study, we assessed the utility of image-guided radiation therapy (IGRT) in the management of patients with painful vertebral hemangioma. MATERIALS AND METHODS: Patients receiving IGRT for the management of painful vertebral hemangioma were evaluated. The total dose was 24 Gy delivered in 12 daily fractions. The verbal numeric scale (VNS) was used for the assessment of pain relief. The median follow-up duration was 13 months (range: 6-24 months). RESULTS: Median preradiotherapy VNS score was 8 (range: 6-10) and median postradiotherapy VNS score was 1 (range: 0-2) for the total 135 patients treated with IGRT at our department for painful vertebral hemangioma. Reduction in VNS scores after IGRT was statistically significant (P < 0.05). CONCLUSION: Our single-center study revealed that IGRT resulted in substantial relief of pain from vertebral hemangioma. Randomized prospective multicenter trials are needed to shed light on the optimal management of patients suffering from pain due to vertebral hemangioma.

Palliative radiotherapy for painful lymph node metastases.

BACKGROUND: There is limited evidence concerning radiotherapy for painful lymph node metastases (PLM). We evaluated the effectiveness of radiotherapy for PLM using the International Consensus Endpoint in a subgroup analysis of a prospective observational study. METHODS: In the primary study, 302 patients received radiotherapy for painful tumors. Among them, those treated with palliative radiotherapy for PLM were analyzed in the present study. We used the Brief Pain Inventory short form to evaluate the intensity of pain and the pain interference in patient's life. We collected the Brief Pain Inventory and analgesic data at baseline and at 1, 2, and 3 months after the start of radiotherapy. Pain response was assessed using the International Consensus Endpoint. Patients were diagnosed with a predominance of other pain (POP) if non-index pain of a malignant or unknown origin was present and had a greater 'worst pain' score than the index pain. RESULTS: Radiotherapy for PLM was performed on 25 patients. In total, 15 (60%) patients experienced a pain response. The pain response rates for evaluable patients were 66%, 67%, and 57% at 1-, 2-, and 3-month follow-ups, respectively. At baseline and at 1, 2, and 3 months, the median index pain scores were 7, 2, 0, and 0.5, respectively. At 1 month, all pain interference scores were significantly reduced from baseline. Four (16%) patients experienced POP within three months. CONCLUSION: Radiotherapy for PLM improved pain intensity and pain interference. Palliative radiotherapy may be a viable treatment option for PLM.