Quality of life issues in patients with bone metastases: A systematic review.

INTRODUCTION: Bones are frequent sites of metastatic disease, observed in 30-75% of advanced cancer patients. Quality of life (QoL) is an important endpoint in studies evaluating the treatments of bone metastases (BM), and many patient-reported outcome tools are available. The primary objective of this systematic review was to compile a list of QoL issues relevant to BM and its interventions. The secondary objective was to identify common tools used to assess QoL in patients with BM, and the QoL issues they fail to address. METHODS: A search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases between 1946 and 27 January 2023 with the keywords "bone metastases", "quality of life", and "patient reported outcomes". Specific QoL issues in original research studies and the QoL tools used were extracted. RESULTS: The review identified the QoL issues most prevalent to BM in the literature. Physical and functional issues observed in patients included pain, interference with ambulation and daily activities, and fatigue. Psychological symptoms, such as helplessness, depression, and anxiety were also common. These issues interfered with patients' relationships and social activities. Items not mentioned in existing QoL tools were related to newer treatments of BM, such as pain flare, flu-like symptoms, and jaw pain due to osteonecrosis. CONCLUSIONS: This systematic review highlights that QoL issues for patients with BM have expanded over time due to advances in BM-directed treatments. If they are relevant, additional treatment-related QoL issues identified need to be validated prospectively by patients and added to current assessment tools.

Translation and validation of the Dutch Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0) to evaluate health-related quality of life in patients with symptomatic spinal metastases.

BACKGROUND: The primary goal of palliative treatment of spinal metastases is to maintain or improve health-related quality of life (HRQOL). We translated and validated a Dutch version of The Spine Oncology Study Group Outcome Questionnaire (SOSGOQ2.0), a valid and reliable 20-item questionnaire to evaluate HRQOL in patients with spinal metastases. METHODS: After cross-cultural translation and adaptation, the questionnaire was pre-tested in fifteen patients referred for spine surgery and/or radiotherapy. This resulted in a final questionnaire that was sent to patients for assessment of internal consistency, construct (i.e., convergent and divergent) validity, discriminative power and test-retest reliability. RESULTS: Overall, 147 patients (mean age 65.6 years, SD = 10.4) completed the questionnaire after a median time of 45.4 months (IQR = 18.9-72.9) after spine surgery and/or radiotherapy. Internal consistency was good for the Physical function, Pain, and Mental health domains (α = 0.87, 0.86, 0.72), but not for Social function (α = 0.04). Good convergent validity was demonstrated except for Social function (rs = 0.37 95%CI = 0.21-0.51). Discriminative power between patients with ECOG performance scores of 0-1 and 2-4 was found on all domains and Neurological function items. Test-retest reliability was acceptable for Physical function, Pain and Mental health (ICC = 0.89 95%CI = 0.81-0.94, ICC = 0.88 95%CI = 0.78-0.93, ICC = 0.68 95%CI = 0.48-0.81), whereas ICC = 0.45 (95%CI = 0.17-0.66) for Social function was below threshold. After removing item 20 from the Social function domain, internal consistency improved, and convergent validity and test-retest reliability were good. CONCLUSION: The Dutch version of the SOSGOQ2.0 questionnaire is a reliable and valid tool to measure HRQOL in patients with spinal metastases. Item 20 was removed to retain psychometric properties.

Prospective Evaluation of the Relationship Between Mechanical Stability and Response to Palliative Radiotherapy for Symptomatic Spinal Metastases.

BACKGROUND: A substantial number of patients with spinal metastases experience no treatment effect from palliative radiotherapy. Mechanical spinal instability, due to metastatic disease, could be associated with failed pain control following radiotherapy. This study investigates the relationship between the degree of spinal instability, as defined by the Spinal Instability Neoplastic Score (SINS), and response to radiotherapy in patients with symptomatic spinal metastases in a multi-institutional cohort. METHODS AND MATERIALS: The SINS of 155 patients with painful thoracic, lumbar, or lumbosacral metastases from two tertiary hospitals was calculated using images from radiotherapy planning CT scans. Patient-reported pain response, available for 124 patients, was prospectively assessed. Pain response was categorized, according to international guidelines, as complete, partial, indeterminate, or progression of pain. The association between SINS and pain response was estimated by multivariable logistic regression analysis, correcting for predetermined clinical variables. RESULTS: Of the 124 patients, 16 patients experienced a complete response and 65 patients experienced a partial response. Spinal Instability Neoplastic Score was associated with a complete pain response (adjusted odds-radio [ORadj] 0.78; 95% confidence interval [CI] 0.62-0.98), but not with an overall pain response (ORadj 0.94; 95% CI 0.81-1.10). CONCLUSIONS: A lower SINS, indicating spinal stability, is associated with a complete pain response to radiotherapy. This supports the hypothesis that pain resulting from mechanical spinal instability responds less well to radiotherapy compared with pain from local tumor activity. No association could be determined between SINS and an overall pain response, which might indicate that this referral tool is not yet optimal for prediction of treatment outcome. IMPLICATIONS FOR PRACTICE: Patients with stable painful spinal metastases, as indicated by a Spinal Instability Neoplastic Score (SINS) of 6 or lower, can effectively be treated with palliative external beam radiotherapy. The majority of patients with (impending) spinal instability, as indicated by a SINS score of 7 or higher, will achieve a (partial) response after palliative radiotherapy; however, some patients might require surgical intervention. Therefore, it is recommended to refer patients with a SINS score of 7 or higher to a spine surgeon to evaluate the need for surgical intervention.

The Effect of Introducing the Spinal Instability Neoplastic Score in Routine Clinical Practice for Patients With Spinal Metastases.

BACKGROUND: Stable spinal metastases are effectively treated with radiotherapy, whereas unstable spinal metastases often need surgical fixation followed by radiotherapy for local control. The Spinal Instability Neoplastic Score (SINS) was developed as a tool to assess spinal neoplastic related instability with the goal of helping to guide referrals among oncology specialists. We compare the average degree of spinal instability between patients with spinal metastases referred for surgery or for radiotherapy and evaluate whether this difference changed after introduction of the SINS in clinical practice. METHODS: All patients with spinal metastases treated with palliative surgery or radiotherapy in the period 2009-2013 were identified in two spine centers. For all patients, the SINS was scored on pretreatment imaging. The SINS before and after introduction of the SINS in 2011 were compared within the surgical and radiotherapy group. Furthermore, the overall SINS was compared between the two groups. RESULTS: The overall SINS was significantly higher in the surgical group, with a mean SINS of 10.7 (median 11) versus 7.2 (median 8) for the radiotherapy group. The mean SINS decreased significantly for both groups after introduction of the SINS in clinical practice from 11.2 to 10.3 in the surgical group and from 8.4 to 7.2 in the radiotherapy group. CONCLUSION: The SINS differed significantly between patients treated with surgery or radiotherapy. The introduction of SINS led to a decrease in SINS score for both groups, suggesting that using SINS in metastatic spinal disease increases awareness for instability and may subsequently result in earlier referrals for surgical intervention. IMPLICATIONS FOR PRACTICE: Spinal metastases can present with varying degrees of mechanical instability. Because unstable spinal metastases may respond insufficiently to palliative radiotherapy and can lead to loss of ambulation, timely detection and appropriate referral are important. The Spinal Instability Neoplastic Score (SINS) may help physicians caring for patients with metastasized disease to identify spinal instability before the onset of neurological deficits. In this study, it was shown that the introduction of SINS in routine practice led to a decrease in spinal instability in radiotherapy and surgical cohorts. The use of SINS may increase awareness of instability and subsequently result in earlier referrals.

Brief Report: Staged-informed Consent in the Cohort Multiple Randomized Controlled Trial Design.

The "cohort multiple randomized controlled trial," a new design for pragmatic trials, embeds multiple trials within a cohort. The cohort multiple RCT is an attractive alternative to conventional RCTs in fields where recruitment is slow, multiple new (competing) interventions for the same condition have to be tested, new interventions are highly preferred by patients and doctors, and the risk of disappointment bias, cross-over, and contamination is considerable. To prevent these unwanted effects, the cohort multiple RCT provides information on randomization to the intervention group/arm only, and only after randomization (i.e., prerandomization). To some, especially in a clinical setting, this is not ethically acceptable. In this article, we argue that prerandomization in the cohort multiple randomized controlled trial (cmRCT) can be avoided by adopting a staged-informed consent procedure. In the first stage, at entry into the cohort, all potential participants are asked for their informed consent to participate in a cohort study and broad consent to be either randomly selected to be approached for experimental interventions or to serve as control without further notice during participation in the cohort. In a second stage, at the initiation of an RCT within the cohort, informed consent to receive the intervention is then only sought in those randomly selected for the intervention arm. At the third stage, after completion of each RCT, all cohort participants receive aggregate disclosure of trial results. This staged-informed consent procedure avoids prerandomization in cmRCT and aims to keep participants actively engaged in the research process.

Comparing conVEntional RadioTherapy with stereotactIC body radiotherapy in patients with spinAL metastases: study protocol for an randomized controlled trial following the cohort multiple randomized controlled trial design.

BACKGROUND: Standard radiotherapy is the treatment of first choice in patients with symptomatic spinal metastases, but is only moderately effective. Stereotactic body radiation therapy is increasingly used to treat spinal metastases, without randomized evidence of superiority over standard radiotherapy. The VERTICAL study aims to quantify the effect of stereotactic radiation therapy in patients with metastatic spinal disease. METHODS/DESIGN: This study follows the 'cohort multiple Randomized Controlled Trial' design. The VERTICAL study is conducted within the PRESENT cohort. In PRESENT, all patients with bone metastases referred for radiation therapy are enrolled. For each patient, clinical and patient-reported outcomes are captured at baseline and at regular intervals during follow-up. In addition, patients give informed consent to be offered experimental interventions. Within PRESENT, 110 patients are identified as a sub cohort of eligible patients (i.e. patients with unirradiated painful, mechanically stable spinal metastases who are able to undergo stereotactic radiation therapy). After a protocol amendment, also patients with non-spinal bony metastases are eligible. From the sub cohort, a random selection of patients is offered stereotactic radiation therapy (n = 55), which patients may accept or refuse. Only patients accepting stereotactic radiation therapy sign informed consent for the VERTICAL trial. Non-selected patients (n = 55) receive standard radiotherapy, and are not aware of them serving as controls. Primary endpoint is pain response after three months. Data will be analyzed by intention to treat, complemented by instrumental variable analysis in case of substantial refusal of the stereotactic radiation therapy in the intervention arm. DISCUSSION: This study is designed to quantify the treatment response after (stereotactic) radiation therapy in patients with symptomatic spinal metastases. This is the first randomized study in palliative care following the cohort multiple Randomized Controlled Trial design. This design addresses common difficulties associated with classic pragmatic randomized controlled trials, such as disappointment bias in patients allocated to the control arm, slow recruitment, and poor generalizability. TRIAL REGISTRATION: The Netherlands Trials Register number NL49316.041.14. ClinicalTrials.gov registration number NCT02364115 . Date of trial registration February 1, 2015.

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.

Remineralization of lytic spinal metastases after radiotherapy.

BACKGROUND CONTEXT: Palliative radiotherapy (RT) can lead to remineralization of osteolytic lesions thereby potentially restoring some of the weight-bearing capacity and preventing vertebral collapse. It is not clear, however, under which circumstances remineralization of osteolytic lesions occurs. PURPOSE: The aim of this study was to investigate the change in bone mineral density in spinal metastases after RT compared to a reference region, and find associated factors. STUDY DESIGN: Retrospective analysis within prospective observational cohort OUTCOME MEASURES: change in bone mineral density measured in Hounsfield Units (HU). PATIENT SAMPLE: patients treated with RT for (painful) bone metastases. METHODS: Patients with spinal metastases were included if computed tomography scans both pre- and post-RT were available. Bone density was measured in HU. A region of interest (ROI) was drawn manually in the metastatic lesion. As a reference, a measurement of bone density in adjacent, unaffected, and non-irradiated vertebrae was used. Factors tested for association were origin of the primary tumor, RT dose and fractionation scheme, and concomitant use of bisphosphonates. RESULTS: A total of 31 patients with 49 spinal metastases, originating from various primary tumors, were included. The median age on baseline was 58 years (IQR: 53-63) and median time between baseline and follow-up scan was 8.2 months (IQR: 3.0-18.4). Difference in HU in the lesion before and after treatment was 146.9 HU (95% CI 68.4-225.4; p<.01). Difference in HU in the reference vertebra between baseline and first follow-up was 19.1 HU (95% CI -47.9 to 86.0; p=.58). Difference between reference vertebrae and metastatic lesions on baseline was -194.1 HU (95% CI -276.2 to -112.0; p<.01). After RT, this difference was reduced to -50.3 HU (95% CI -199.6 to 99.0; p=.52). Patients using bisphosphonates showed a greater increase in HU, 194.1 HU versus 60.6 HU, p=.01. CONCLUSIONS: Palliative radiation of osteolytic lytic spinal metastases is positively associated with an increased bone mineral density at follow-up. The use of bisphosphonates was linked to an increased bone mineral density when used during or after RT.

Appropriateness of the 30-day expected mortality metric in palliative radiation treatment: a narrative review.

BACKGROUND AND OBJECTIVE: The 30-day expected mortality rate is frequently used as a metric to determine which patients benefit from palliative radiation treatment (RT). We conducted a narrative review to examine whether its use as a metric might be appropriate for patient selection. METHODS: A literature review was conducted to identify relevant studies that highlight the benefits of palliative RT in timely symptom management among patients with a poor performance status, the accuracy of predicting survival near the end of life and ways to speed up the process of RT administration through rapid response clinics. KEY CONTENT AND FINDINGS: Several trials have demonstrated substantial response rates for pain and/or bleeding by four weeks and sometimes within the first two weeks after RT. Models of patient survival have limited accuracy, particularly for predicting whether patients will die within the next 30 days. Dedicated Rapid Access Palliative RT (RAPRT) clinics, in which patients are assessed, simulated and treated on the same day, reduce the number of patient visits to the radiation oncology department and hence the burden on the patient as well as costs. CONCLUSIONS: Single-fraction palliative RT should be offered to eligible patients if they are able to attend treatment and could potentially benefit from symptom palliation, irrespective of predicted life expectancy. We discourage the routine use of the 30-day mortality as the only metric to decide whether to offer RT. More common implementation of RAPRT clinics could result in a significant benefit for patients of all life expectancies, but particularly those having short ones.

Stereotactic body radiation therapy versus conventional external beam radiotherapy for spinal metastases: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: This study aimed to compare SBRT and cEBRT for treating spinal metastases through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, EMBASE and Cochrane Library were searched up to 6 May 2023 for RCTs comparing SBRT and cEBRT for spinal metastases. Overall and complete pain response, local progression, overall survival, quality of life and adverse events were extracted. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) for dichotomous outcomes, and hazard ratios (HRs) for time-to-event outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic. RESULTS: Three RCTs were identified involving 642 patients. No differences were seen in overall pain response comparing SBRT and cEBRT (RR at 3 months: 1.12, 95% CI, 0.74-1.70, p = 0.59; RR at 6 months: 1.29, 95% CI, 0.97-1.72, p = 0.08). Only two of three studies presented complete pain response data. SBRT demonstrated a statistically significant improvement in complete pain response compared to cEBRT (RR at 3 months: 2.52; 95% CI, 1.58-4.01; P < 0.0001; RR at 6 months: 2.48; 95% CI, 1.23-4.99; P = 0.01). There were no significant differences in local progression and overall survival. Adverse events were similar, except for any grade radiation dermatitis, which was significantly lower in SBRT arm (RR 0.17, 95% CI 0.03-0.96, P = 0.04). CONCLUSION: SBRT is a safe treatment option for spine metastases. It may provide better complete pain response compared to cEBRT. Additional trials are needed to determine the potential benefits of SBRT in specific patient subsets.

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.

ESTRO ACROP guidelines for external beam radiotherapy of patients with complicated bone metastases.

This is the second part of the guidelines on the management of bone metastases. In the first part, the diagnosis and management of uncomplicated bone metastases have been addressed. Bone metastases may significantly reduce quality of life due to related symptoms and possible complications. The most common symptoms include pain and neurologic deficits. The most serious complications of bone metastases are skeletal-related events (SRE), defined as pathologic fracture, spinal cord compression, pain, or other symptoms requiring an urgent intervention such as surgery or radiotherapy. Diffuse bone metastases may lead to hypercalcaemia that can be fatal if untreated. The growing access to modern diagnostic tools allows early detection of asymptomatic bone metastases that could be successfully managed with local treatment if oligometastatic or systemic treatment for diffuse bone metastases to try to avoid the development of SRE.

Accumulated bladder wall dose is correlated with patient-reported acute urinary toxicity in prostate cancer patients treated with stereotactic, daily adaptive MR-guided radiotherapy.

BACKGROUND AND PURPOSE: Magnetic resonance (MR)-guided linear accelerators (MR-Linac) enable accurate estimation of delivered doses through dose accumulation using daily MR images and treatment plans. We aimed to assess the association between the accumulated bladder (wall) dose and patient-reported acute urinary toxicity in prostate cancer (PCa) patients treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: One-hundred-and-thirty PCa patients treated on a 1.5 T MR-Linac were included. Patients filled out International Prostate Symptom Scores (IPSS) questionnaires at baseline, 1 month, and 3 months post-treatment. Deformable image registration-based dose accumulation was performed to reconstruct the delivered dose. Dose parameters for both bladder and bladder wall were correlated with a clinically relevant increase in IPSS (≥ 10 points) and/or start of alpha-blockers within 3 months using logistic regression. RESULTS: Thirty-nine patients (30%) experienced a clinically relevant IPSS increase and/or started with alpha-blockers. Bladder D5cm3, V10-35Gy (in %), and Dmean and Bladder wall V10-35Gy (cm3 and %) and Dmean were correlated with the outcome (odds ratios 1.04-1.33, p-values 0.001-0.044). Corrected for baseline characteristics, bladder V10-35Gy (in %) and Dmean and bladder wall V10-35Gy (cm3 and %) and Dmean were still correlated with the outcome (odds ratios 1.04-1.30, p-values 0.001-0.028). Bladder wall parameters generally showed larger AUC values. CONCLUSION: This is the first study to assess the correlation between accumulated bladder wall dose and patient-reported urinary toxicity in PCa patients treated with MR-guided SBRT. The dose to the bladder wall is a promising parameter for prediction of patient-reported urinary toxicity and therefore warrants prospective validation and consideration in treatment planning.

Most patients reported positively or neutrally of having served as controls in the trials within cohorts design.

OBJECTIVES: To evaluate patients' experience of having served as controls without a notification at the time of randomization in the context of the trial within cohorts (TwiCs) design. METHODS: Patients were asked for their opinion on having served as controls in TwiCs, before and after having been provided the trial results. Patients had provided broad consent to randomization at cohort entry and had served as controls in one of two TwiCs (an exercise program after breast cancer treatment or radiotherapy dose-escalation for rectal cancer). RESULTS: Two to 6 years after cohort entry, 15% (n = 16) of all patients remembered having provided broad consent to randomization. Before disclosure of trial results, 47% (n = 52) of patients thought positively, 45% (n = 50) neutrally, and 2% (n = 2) negatively of having served as controls in one of the two trials. Seventeen percent (n = 18) of patients were positive, 65% (n = 71) neutral, and 11% (n = 12) negative about not having been notified when serving as controls. The survey results were comparable after disclosure of trial results. CONCLUSIONS: These results support the use of the TwiCs design with the staged-informed consent procedure. Keeping patients engaged and aware of the consents provided might further improve patients' experience of serving as controls in TwiCs.

Clinical utility of convolutional neural networks for treatment planning in radiotherapy for spinal metastases.

BACKGROUND AND PURPOSE: Spine delineation is essential for high quality radiotherapy treatment planning of spinal metastases. However, manual delineation is time-consuming and prone to interobserver variability. Automatic spine delineation, especially using deep learning, has shown promising results in healthy subjects. We aimed to evaluate the clinical utility of deep learning-based vertebral body delineations for radiotherapy planning purposes. MATERIALS AND METHODS: A multi-scale convolutional neural network (CNN) was used for automatic segmentation and labeling. Two approaches were tested: the combined approach using one CNN for both segmentation and labeling, and the sequential approach using separate CNN's for these tasks. Training and internal validation data included 580 vertebrae, external validation data included 202 vertebrae. For quantitative assessment, Dice similarity coefficient (DSC) and Hausdorff distance (HD) were used. Axial slices from external images were presented to radiation oncologists for subjective evaluation. RESULTS: Both approaches performed comparably during the internal validation (DSC: 96.7%, HD: 3.6 mm), but the sequential approach proved more robust during the external validation (DSC: 94.5% vs 94.4%, p < 0.001, HD: 4.5 vs 7.1 mm, p < 0.001). Subsequently, subjective evaluation of this sequential approach showed that experienced radiation oncologists could distinguish automatic from human-made contours in 63% of cases. They rated automatic contours clinically acceptable in 77% of cases, compared to 88% of human-made contours. CONCLUSION: We present a feasible approach for automatic vertebral body delineation using two variants of a multi-scale CNN. This approach generates high quality automatic delineations, which can save time in a clinical radiotherapy workflow.

Quality of Life After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases.

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, 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 χ2 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.

Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases-A Phase 2 Randomized Controlled Trial Within a Prospective Cohort.

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 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 × 18 Gy, 3 × 10 Gy, or 5 × 7 Gy), which they could accept or refuse. Patients who refused SBRT underwent standard cRT (1 × 8 Gy, 5 × 4 Gy, or 10 × 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 SBRT arm 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 SBRT arm (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.

Oncology patients were found to understand and accept the Trials within Cohorts design.

BACKGROUND AND OBJECTIVE: The Trials within Cohorts design aims to reduce recruitment difficulties and disappointment bias in pragmatic trials. On cohort enrollment, broad informed consent for randomization is asked, after which cohort participants can be randomized to interventions or serve as controls without further notification. We evaluated patients' recollection, understanding, and acceptance of broad consent in a clinical oncology setting. METHODS: We surveyed 610 patients with cancer participating in ongoing TwiCs; 482 patients (79%) responded, of which 312 patients shortly after cohort enrollment, 108 patients after randomization to an intervention (12-18 months after cohort enrollment), and a random sample of 62 cohort participants who had not been selected for interventions (1-6 months after cohort enrollment). RESULTS: Shortly after providing cohort consent, 76% of patients (238/312) adequately remembered whether they had given broad consent for randomization. Of patients randomly offered interventions, 76% (82/108) remembered giving broad consent for randomization; 41% (44/108) understood they were randomly selected, 44% (48/108) were not interested in selection procedures, and 10% (11/108) did not understand selection was random. Among patients not selected for interventions, 42% (26/62) understood selection was random; 89% felt neutral regarding the scenario of "not being selected for an intervention while your data were being used in comparison with patients receiving interventions," 10% felt reassured (6/62) and 2% scared/insecure (2/62). CONCLUSION: Patients adequately remember giving broad consent for randomization shortly after cohort enrollment and after being offered an intervention, but recollection is lower in those never selected for interventions. Patients are acceptant of serving as control without further notifications.