Practice and principles of stereotactic body radiation therapy for spine and non-spine bone metastases.

Radiotherapy is the dominant treatment modality for painful spine and non-spine bone metastases (NSBM). Historically, this was achieved with conventional low dose external beam radiotherapy, however, stereotactic body radiotherapy (SBRT) is increasingly applied for these indications. Meta-analyses and randomized clinical trials have demonstrated improved pain response and more durable tumor control with SBRT for spine metastases. However, in the setting of NSBM, there is limited evidence supporting global adoption and large scale randomized clinical trials are in need. SBRT is technically demanding requiring careful consideration of organ at risk tolerance, and strict adherence to technical requirements including immobilization, simulation, contouring and image-guidance procedures. Additional considerations include follow up practices after SBRT, with appropriate imaging playing a critical role in response assessment. Finally, there is renewed research into promising new technologies that may further refine the use of SBRT in both spinal and NSBM in the years to come.

The Role of Post-Operative Radiotherapy for Non-Spine Bone Metastases (NSBMs).

Non-spine bone metastases (NSBMs) can cause significant morbidity and deterioration in the quality of life of cancer patients. This paper reviews the role of post-operative radiotherapy (PORT) in the management of NSBMs and provides suggestions for clinical practice based on the best available evidence. We identified six retrospective studies and several reviews that examined PORT for NSBMs. These studies suggest that PORT reduces local recurrence rates and provides effective pain relief. Based on the literature, PORT was typically delivered as 20 Gy in 5 fractions or 30 Gy in 10 fractions within 5 weeks of surgery. Complete coverage of the surgical hardware is an important consideration when designing an appropriate radiation plan and leads to improved local control. Furthermore, the integration of PORT in a multidisciplinary team with input from radiation oncologists and orthopedic surgeons is beneficial. A multimodal approach including PORT should be considered for an NSBM that requires surgery. However, phase III studies are needed to answer many remaining questions and optimize the management of NSBMs.

Interobserver variability in gross tumor volume contouring in non-spine bone metastases.

Background and Aim: The optimal imaging test for gross tumor volume (GTV) delineation in non-spine bone metastases has not been defined. The use of stereotactic body radiotherapy (SBRT) requires accurate target delineation. Magnetic resonance imaging (MRI) and/or 18fludesoxyglucose positron emission tomography (18FDG-PET) allow for better visualization of the extent of bone metastases and optimizes the accuracy of tumor delineation for stereotactic radiotherapy compared to computed tomography (CT) alone. We evaluated the interobserver agreement in GTV of non-spine bone metastases in a single center and compared MRI and/or 18FDG-PET and CT in GTV delineation. Methods: Anonymous CT and MRI and/or 18FDG-PET obtained from 10 non-spine bone metastases were analyzed by six radiation oncologists at our center. Images acquired by CT and MRI and/or 18FDG-PET were used to delineate 10 GTVs of non-spine bone metastases in the pelvis, extremities, and skull. The cases showed different characteristics: blastic and lytic metastases, and different primary cancers (lung, breast, prostate, rectum, urothelial, and biliary). In both CT and MRI and/or 18FDG-PET, the GTV volumes were compared. The index of agreement was evaluated according to Landis and Koch protocol. Results: The GTV volume as defined on MRI was in all cases larger or at least as large as the GTV volume on CT (P=0.25). The median GTV volume on MRI was 3.15 cc (0.027-70.64 cc) compared to 2.8 cc on CT (0.075-77.95 cc). Interobserver variance and standard deviation were lower in CT than MRI (576.3 vs. 722.2 and 24.0 vs. 26.9, respectively). The level of agreement was fair (kappa=0.36) between CT and MRI. The median GTV volume on 18FDG-PET in five patients was 5.8 cc (0.46-64.17 cc), compared to 4.1 cc on CT (0.99-54.2 cc) (P=0.236). Interobserver variance and standard deviation in CT, MRI, and 18FDG-PET were 576.3 versus 722.2 versus 730.5 and 24 versus 26.9 versus 27.0, respectively. The level of agreement was slight (kappa=0.08) between CT and 18FDG-PET. Conclusions: Interobserver variance in non-spine bone metastases was equal when MRI and PET were compared to CT. CT was associated with the lowest variance and standard deviation. Compared to CT GTVs, the GTVs rendered from MRI images had fair agreement, while the GTVs rendered from 18FDG-PET had only slight agreement. Relevance for Patients: The delimitation of the treatment volume in non-spine bone metastases with SBRT is important for the results determining its efficacy. It is therefore essential to know the variability and to manage it to achieve the highest quality of treatment.

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

(1) Background: The superiority of stereotactic body radiotherapy (SBRT) over conventional external beam radiotherapy (cEBRT) in terms of pain palliation for bone metastases remains controversial. (2) Methods: This propensity score-matched study compared the overall pain response (OR) 3 months after radiotherapy among patients with painful (≥2 points on a 0-to-10 scale) non-spine bone metastases. Patients with lesions that were treated with SBRT or cEBRT and whose pain scores were evaluated 3 months after radiotherapy were included in this study. Pain response was evaluated according to the International Consensus Criteria. (3) Results: A total of 234 lesions (SBRT, n = 129; cEBRT, n = 105) were identified in our institutional database. To reduce the confounding effects, 162 patients were selected using a propensity score-matched analysis (n = 81 for each treatment). The OR rate at 3 months after SBRT was significantly higher than that after cEBRT (76.5% vs. 56.8%; p = 0.012). A noteworthy finding of our study is that the same trend was observed even after 6 months (75.9% vs. 50.0%; p = 0.011). The 1-year local failure rates after SBRT and cEBRT were 10.2% and 33.3% (p < 0.001), respectively. (4) Conclusions: Our findings suggest that SBRT is superior to cEBRT for pain palliation in patients with non-spine bone metastases.

SEOR SBRT-SG stereotactic body radiation therapy consensus guidelines for non-spine bone metastasis

The use of stereotactic body radiation therapy (SBRT) to treat non-spine bone metastases (NSBM) is becoming increasingly common in clinical practice. The clinical advantages of SBRT include good pain control and high local control rates, although only limited data are available. The Spanish Society of Radiation Oncology (SEOR) SBRT group recently convened a task force of experts in the field to address key questions related to SBRT for NSBM, including treatment indications, planning, techniques, and dose fractionation. The task force reviewed the available literature to develop evidence-based recommendations for the safe application of NSBM SBRT and to standardize and optimize SBRT processes. The present document provides a comprehensive analysis of the available data, including ongoing clinical trials and controversies, providing clinically applicable recommendations.

SEOR SBRT-SG stereotactic body radiation therapy consensus guidelines for non-spine bone metastasis.

The use of stereotactic body radiation therapy (SBRT) to treat non-spine bone metastases (NSBM) is becoming increasingly common in clinical practice. The clinical advantages of SBRT include good pain control and high local control rates, although only limited data are available. The Spanish Society of Radiation Oncology (SEOR) SBRT group recently convened a task force of experts in the field to address key questions related to SBRT for NSBM, including treatment indications, planning, techniques, and dose fractionation. The task force reviewed the available literature to develop evidence-based recommendations for the safe application of NSBM SBRT and to standardize and optimize SBRT processes. The present document provides a comprehensive analysis of the available data, including ongoing clinical trials and controversies, providing clinically applicable recommendations.

Fracture risk following stereotactic body radiotherapy for long bone metastases.

BACKGROUND: Stereotactic body radiotherapy is a new treatment modality for long bone metastasis and has not been discussed in literature. We aimed to clarify stereotactic body radiotherapy outcomes for long bone metastases. METHODS: Data of patients receiving stereotactic body radiotherapy for long bone metastases (July 2016-November 2020) were retrospectively reviewed. The prescribed dose was 30 or 35 Gy in five fractions. The endpoints were local failure and adverse effects. Local failure was defined as radiological tumor growth within the irradiation field. Adverse effects were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5. RESULTS: Nineteen osseous lesions in 17 patients were assessed. The target lesions included 13 femoral, 4 humeral and 2 radial lesions. The median follow-up duration was 14 (range, 3-62) months. The 12- and 18-month local failure rates were 0 and 11%, respectively. Following 2 and 46 months of stereotactic body radiotherapy, two lesions (11%) resulted in painful femoral fractures (grade 3). Both patients underwent bipolar hip arthroplasty and could walk normally after surgery. In the late phase, one patient developed radiculopathy (almost complete paralysis of grasp) and another developed grade 2 limb edema. Other grade 2 or more severe acute and late toxicities were not observed during the follow-up period. CONCLUSIONS: Stereotactic body radiotherapy for long bone metastases achieved excellent local control and caused two femoral fractures. We argue that stereotactic body radiotherapy for curative intent should not be contraindicated in long bone oligometastasis because fractures do not directly contribute to life expectancy.

SBRT in non-spine bone metastases: a literature review.

Stereotactic Body Radiotherapy (SBRT) is a technique for delivering high doses of radiation to tumors while preserving the normal tissues located around this area. Bone metastases are frequent in cancer patients. They can be distressingly painful or may cause pathological fractures. Radiation therapy is a fundamental aspect of treatment for bone metastases. The objective of this study is to analyze the literature on non-spine bone metastasis treated with SBRT, including immobilization, volume delineation, dose and fractionation, local control, side effects, and assessment of response after treatment. Full-text articles written in English language and published in the last 10 years were included in this review and were accessible on PubMed and MEDLINE. We examined 78 articles. A total of 40 studies were included in this review. Most were retrospective studies. The articles included were evaluated for content and validation. The immobilization systems and imaging tests used for tumor delimitation were variable between studies. The use of CTV (Clinical Target Volume) has not been defined. Doses and fractions were variable from 15 to 24 Gy/1 fraction to 24-50 Gy in 3-5 fractions, with local control being around 90% with a low rate of side effects. We review state of the art in SBRT non-spine metastases. SBRT can result in better local control and pain management in non-spine bone metastases patients. We need more research in volume delineation determining whether or not to use CTV and the role of MRI in volume contouring, optimal doses, and fractionation according to histology and a reliable response assessment tool. Studies that compare SBRT to conventional radiotherapy in local control and pain control are needed.

A phase I dose-escalation trial of stereotactic ablative body radiotherapy for non-spine bone and lymph node metastases (DESTROY-trial).

BACKGROUND: In an oligometastatic setting, metastasis-directed treatment could render patients disease free, possibly for a protracted interval. Stereotactic ablative radiotherapy (SABR) is one of the treatment modalities that can be offered to these patients. In addition, the radiobiological qualities of SABR are promising for the use in perceived radioresistant tumours. There is also emerging evidence that SABR can stimulate the immune response, and a specific therapeutic window may exist for the optimal use of radiotherapy as an immune adjuvant. However, when SABR is considered for non-spine bone or lymph node metastases, the optimal fractionation schedule is not yet known. METHODS: The DESTROY-trial is a non-randomized prospective phase I trial determining a regimen of choice for patients with non-spine bone and lymph node metastases. A total of 90 patients will be included in three different treatment regimens. They will be offered stereotactic ablative radiotherapy in 5, 3 or 1 fractions. Dose-limiting toxicity will be recorded as primary endpoint. Acute and late toxicity, local response and local recurrence, and progression-free survival are secondary endpoints. Liquid biopsies will be collected throughout the course of this study from the second fractionation schedule on. DISCUSSION: Despite its almost universal use in (oligo-)metastatic patients, the level of evidence supporting radical local treatment in general, and stereotactic radiotherapy in particular, is low. This prospective phase I trial will evaluate different SABR regimens for metastases and the differences in immune-stimulatory effects. TRIAL REGISTRATION: The Ethics committee of the GZA Hospitals (B099201732915) approved this study on 05/07/2017. Amendment for translational research was approved on 06/02/2018. Trial registered on Clinicaltrials.gov ( NCT03486431 ) on 03/04/2018 - Retrospectively registered.

Radiological changes on CT after stereotactic body radiation therapy to non-spine bone metastases: a descriptive series.

BACKGROUND: In recent years, stereotactic body radiation therapy (SBRT) has become increasingly used for the management of non-spine bone metastases. Few studies have examined the radiological changes in bone metastases after treatment with SBRT and there is no consensus about what constitutes radiologic response to therapy. This article describes various changes on CT after SBRT to non-spine bone metastases in eight selected cases. METHODS: A retrospective review was conducted for patients treated with SBRT to non-spine bone metastases between November 2011 and April 2014 at Sunnybrook Health Sciences Centre. A musculoskeletal radiologist identified eight illustrative cases of interest and provided a description of the findings. RESULTS: Different radiological changes following SBRT were described, including: remineralization of lytic bone metastases, demineralization of sclerotic bone metastases, pathologic fracture, size progression and response in different lesions, as well as lung fibrosis after SBRT to a rib metastasis. CONCLUSIONS: We reviewed the radiological images of eight selected cases after SBRT to nonspine bone metastases and a number of characteristic findings were highlighted. We recommend future studies to correlate radiologic changes with clinical outcomes including pain relief, toxicity and long-term local control.