Non-spine Bone Metastases Research Articles

Shifting the Landscape of Spine and Non-Spine Bone Metastases: A Review of Stereotactic Body Radiotherapy.

Both spine and nonspine bone metastases are frequent sites of spread from solid organ malignancies. As bone metastases frequently cause significant morbidity for patients, it is critical to offer a treatment that can achieve rapid and durable symptomatic relief and local control, without being associated with serious risks of toxicity. Conventional palliative radiation therapy has a key treatment component in the multidisciplinary management of these patients; however, over the past decade, it has evolved to routinely deliver high biologically effective doses with precision in the form of stereotactic body radiation therapy. This change in paradigm is a result of the shifting landscape in cancer care, such that short-term pain relief is no longer the sole therapeutic aim for selected patients, and durable symptom relief and local tumor control are the goals. This review discusses the randomized prospective evidence, ongoing trials, approach to surveillance imaging, and treatment delivery for stereotactic body radiation therapy, to both spine and nonspine bone metastases, with a specific section on sacral metastases.

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.

Predictors of pathologic fracture and local recurrence following stereotactic body radiation therapy to 505 non-spine bone metastases

PurposeStereotactic Body Radiation Therapy (SBRT) is increasingly applied to treat non-spine bone metastases (NSBM) though data remains limited on this approach. In this retrospective study, we report outcomes and predictors of local failure (LF) and pathological fracture (PF) post-SBRT for NSBM using a mature single-institution database. MethodsPatients with NSBM treated with SBRT between 2011 and 2021 were identified. The primary objective was to assess the rates of radiographic LF. Secondary objectives were to assess the rates of in-field PF, overall survival (OS), and late grade ≥ 3 toxicity. Competing risks analysis was used to assess rates of LF and PF. Univariable regression and multivariable regression (MVR) were performed to investigate predictors of LF and PF. ResultsA total of 373 patients with 505 NSBM were included in this study. Median follow-up was 26.5 months. The cumulative incidence of LF at 6, 12, and 24 months were 5.7%, 7.9%, and 12.6%, respectively. The cumulative incidence of PF at 6, 12, and 24 months were 3.8%, 6.1%, and 10.9%, respectively. Lytic NSBM (HR = 2.18; p < 0.01), a lower biologically effective dose (HR = 1.11 per 5 Gy10 decrease; p = 0.04), and a PTV ≥ 54 cc (HR = 4.32; p < 0.01) predicted for a higher risk of LF on MVR. Lytic NSBM (HR = 3.43; p < 0.01), mixed (lytic/sclerotic) lesions (HR = 2.70; p = 0.04), and rib metastases (HR = 2.68; p < 0.01) predicted for a higher risk of PF on MVR. ConclusionSBRT is an effective modality to treat NSBM with high rates of radiographic local control with an acceptable rate of PF. We identify predictors of both LF and PF that can serve to inform practice and trial design.

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.

PSMA-PET/CT-Based Stereotactic Body Radiotherapy (SBRT) in the Treatment of Uncomplicated Non-Spinal Bone Oligometastases from Prostate Cancer

Background and purpose: Stereotactic body radiotherapy (SBRT) has a consolidated role in the treatment of bone oligometastases from prostate cancer (PCa). While the evidence for spinal oligometastases SBRT was robust, its role in non-spinal-bone metastases (NSBM) is not standardized. In fact, there was no clear consensus about dose and target definition in this setting. The aim of our study was to evaluate efficacy, toxicity, and the pattern of relapse in SBRT delivered to NSBM from PCa. Materials and methods: From 2016 to 2021, we treated a series of oligo-NSBM from PCa with 68Ga-PSMA PET/CT-guided SBRT. The primary endpoint was local progression-free survival (LPFS). The secondary endpoints were toxicity, the pattern of intraosseous relapse, distant progression-free survival (DPFS), polimetastases-free survival (PMFS), and overall survival (OS). Results: a total of 150 NSBM in 95 patients were treated with 30–35 Gy in five fractions. With a median follow-up of 26 months, 1- and 3 years LPFS was 96.3% and 89%, respectively. A biologically effective dose (BED) ≥ 198 Gy was correlated with improved LPFS (p = 0.007). Intraosseous relapse occurred in eight (5.3%) cases. Oligorecurrent disease was associated with a better PMFS compared to de novo oligometastatic disease (p = 0.001) and oligoprogressive patients (p = 0.007). No grade ≥ 3 toxicity occurred. Conclusion: SBRT is a safe and effective tool for NSBM from PCa in the oligometastatic setting. Intraosseous relapse was a relatively rare event. Predictive factors of the improved outcomes were defined.

Metastasectomy of spinal lesions from thyroid carcinomas

Patients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas. We collected data on 22 patients with DTC (16 follicular and six papillary carcinomas) and one patient with medullary carcinoma who underwent complete surgical resection of SMs at our institution between July 1992 and July 2017, with a minimum postoperative follow-up of five years. The cancer-specific survival (CSS) from the first spinal metastasectomy to death or the last follow-up was determined using Kaplan-Meier analysis. Potential factors associated with survival were evaluated using the log-rank test. We analyzed the clinical parameters and outcome data, including pre- and postoperative disability (Eastern Cooperative Oncology Group PS 3), lung and non-spinal bone metastases, and history of radioiodine and kinase inhibitor therapies. Lung and other bone metastases at the time of surgery were observed in ten and eight patients, respectively. Three patients experienced local tumour recurrences at the operated site. The five- and ten-year CSS rates in the 22 patients with DTC were 77% and 52%, respectively. Pre- and postoperative disability and operative site tumour recurrence were identified as risk factors for short postoperative survival. Metastasectomy for resectable SM from DTC yielded favourable results and has the potential to improve survival.

Stereotactic Body Radiation Therapy for Non-Spine Bone Metastases: Local Control and Fracture Risk

<h3>Purpose/Objective(s)</h3> Stereotactic Body Radiation Therapy (SBRT) is increasingly being utilized to treat non-spine bone metastases (NSBM) with both palliative and radical intent. There remains limited data on the long-term outcomes and toxicities and, therefore, we report mature results from our institutional database. <h3>Materials/Methods</h3> Patients with NSBM who were treated with SBRT were identified from 2011 to 2021. The primary endpoint was radiographic local failure (LF). Secondary endpoints included rate of in-field pathologic fracture (PF), overall survival (OS), and late (>3 months post-SBRT) grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). Competing risks analysis was used to assess rates of LF and PF. OS was estimated using the Kaplan-Meier method. Univariable regression (UVR) and multivariable regression (MVR) were performed to investigate predictive factors for LF and PF. <h3>Results</h3> A total of 373 patients with 505 NSBM were included in this study. Primary indications for SBRT included oligometastatic disease (52.6%), pain relief (23.8%), and oligoprogression (19.7%). Median follow-up was 26.5 months (range: 3.0-128.3 months). The most common primary histologies included prostate (33.7%), RCC (20.7%), breast (16.9%), and lung (14.8%). The two most common NSBM sites were pelvic (42.3%) and rib (30.5%). Of all NSBM, 217 (42.7%) were lytic and 230 (45.3%) were symptomatic. The most common dose prescriptions were 35 Gy in 5 fractions (33.3%) and 24 Gy in 2 fractions (25.2%). The cumulative incidence of LF at 6, 12, and 24 months were 5.7%, 7.9%, and 12.6%, respectively. The cumulative incidence of PF at 6, 12, and 24 months were 3.8%, 6.1%, and 10.9%, respectively. There were 3 instances of late grade ≥3 toxicity: 1 grade 3 osteonecrosis, 1 grade 3 peripheral neuropathy, and 1 grade 5 bowel fistula. Median OS was 53.9 months (95% confidence interval: 45.3-63.2 months). Lytic NSBM (HR=2.20; p<0.01), symptomatic NSBM (HR=2.15; p<0.01), and those with a larger PTV (HR=1.01; p=0.04) were at higher risk of LF on MVR. Lytic lesions (HR=3.43; p<0.01), mixed (lytic/sclerotic) lesions (HR=2.70; p=0.04), and rib metastases (HR=2.68; p<0.01) were at a higher risk of PF on MVR. <h3>Conclusion</h3> SBRT is an effective modality to treat NSBM with high rates of radiographic local control with an acceptable rate of fracture. We identify predictors of both LF and PF that can serve to inform practice.

Stereotactic body radiation therapy for spine and non-spine bone metastases. GETUG (french society of urological radiation oncologists) recommendations using a national two-round modified Delphi survey

Backround and purposeThe relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methodsAfter a comprehensive litterature review, 97 recommandation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65–74 % agreements. Any statement without consensus at round one was re-submitted in round two. ResultsTweny-one out of 29 (72.4%) surveyed GETUG investigators responded to both rounds. Consensus was achieved for 91/97 statements (93.8%) allowing the edition of comprehensive guidelines encompassing all aspects of SBM and NSBM SBRT planning and delivery: patients selection (19 statements), treatment preparation (14 statements), target volume delineation (18 statements), dose and fractionation (11 statements), prescription and dose objectives (9 statements), organs at risk dose constraints (15 statements) and image guided radiation therapy (11 statements). ConclusionGETUG guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocol recommendations in ongoing and further GETUG clinical trials.

Response assessment after stereotactic body radiation therapy for spine and non-spine bone metastases: results from a single institutional study

BackgroundThe use of stereotactic body radiation therapy (SBRT) for tumor and pain control in patients with bone metastases is increasing. We report response assessment after bone SBRT using radiological changes through time and clinical examination of patients.MethodsWe analyzed retrospectively oligo-metastatic/progressive patients with bony lesions treated with SBRT between 12/2008 and 10/2018, without in-field re-irradiation, in our institution. Radiological data were obtained from imaging modalities used for SBRT planning and follow-up purposes in picture archiving and communication system and assessed by two independent radiologists blind to the time of treatment. Several radiological changes were described. Radiographic response assessment was classified according to University of Texas MD Anderson Cancer Center criteria. Pain response and the neurological deficit were captured before and at least 6 months after SBRT.ResultsA total of 35 of the 74 reviewed patients were eligible, presenting 43 bone metastases, with 51.2% (n = 22) located in the vertebral column. Median age at the time of SBRT was 66 years (range 38–84) and 77.1% (n = 27) were male. Histology was mainly prostate (51.4%, n = 18) and breast cancer (14.3%, n = 5). Median total radiation dose delivered was 24 Gy (range 24–42), in three fractions (range 2–7), prescribed to 70–90% isodose-line. After a median follow-up of 1.8 years (range < 1–8.2) for survivors, complete or partial response, stable, and progressive disease occurred in 0%, 11.4% (n = 4), 68.6% (n = 24), and 20.0% (n = 7) of the patients, respectively. Twenty patients (57.1%) died during the follow-up time, all from disease progression, yet 70% (n = 14) from this population with local stable disease after SBRT. From patients who were symptomatic and available for follow-up, almost half (44.4%) reported pain reduction after SBRT.ConclusionsEighty percent of the patients showed local control after SBRT for bone metastases. Pain response was favorable. For more accurate response assessment, comparing current imaging modalities with advanced imaging techniques such as functional MRI and PET/CT, in a prospective and standardized way is warranted.Trial registration Retrospectively registered.

Personalized Treatment Selection Leads to Low Rates of Local Salvage Therapy for Bone Metastases

Local therapy for patients with nonspine bone metastases is evolving, with data supporting the use of single-fraction treatments, and more recently, showing possible benefit from stereotactic body radiation therapy (SBRT). However, the rate of local salvage therapy (LST) after each technique has not been characterized in real-world clinic settings where patients are selected at physician discretion. We examined rates of LST in patients with nonspine bone metastases. We reviewed records of RT for nonspine bone metastases at our institution from January 1, 2016, to December 31, 2018. We defined LST as the first occurrence of RT or surgery for oncologic progression to a bone metastasis after initial RT. Cumulative incidence functions for retreatment were generated. We conducted multivariate analysis to identify variables associated with LST. A total of 1754 patients were analyzed, with median follow-up of 16.2 months (range, 0-36.8 months). Of all episodes of RT, 51.5% were multifraction external beam radiation therapy (EBRT), 7.0% were single-fraction EBRT, and 41.4% were SBRT. Altogether, 88 patients (5.0%) required LST, with an incidence at 6 months of 2.5%. Incidence of LST at 6 months was 2.1% for SBRT, 5.3% for single-fraction conventional regimens, and 2.4% for multifraction conventional regimens (P=.26). Patients of younger age, who had a higher Karnofsky performance status, and/or who had lesions in the pelvis had a higher risk of retreatment. In this large institutional cohort, the rate of LST was low, with no difference between RT techniques. The findings indicated that SBRT for patients at high risk for treatment failure may reduce the rate of retreatment overall. When treatment modality was selected based on patient characteristics, rates of LST were lower than when treatment was randomly selected.

Radiation Oncology-Specific Surveillance After Palliative Radiation Treatment for Spine and Non-Spine Bone Metastases

Palliative radiation therapy (RT) can be an effective tool for bone metastases. NCCN guidelines recommend imaging every 3 months after RT for spine metastases (SM), yet no standard surveillance guidelines exist after RT for non-spine bone metastases (NSBM). We sought to evaluate factors associated with radiation oncology-specific follow-up after palliative RT.In a large single-institution retrospective cohort analysis, we identified all patients receiving RT for bone metastases by ICD-10 codes and RT prescription from 2017-2019. Demographic, clinical, and RT data were collected. Overall survival (OS) was calculated using Kaplan-Meier analysis. Factors associated with urgent care (UC) evaluation and radiation oncology follow-up were evaluated with multivariable logistic regression among patients surviving or followed to 3 months post-RT.Overall, 3082 patients (39% NSBM, 61% SM) received RT for bone metastases. Within 3 months of RT, 49% had radiation oncology follow-up, 79% underwent imaging, and 27% were seen in the UC. For patients with NSBM, follow-up CT was most common (55%) while for SM, MRI and CT were common (both 54%). Median OS was 10.0 months for SM (95% CI 8.9-11.0) and 13.5 months for NSBM (95% CI 11.5-15.5), with 1343 (71%) SM patients and 923 (77%) NSBM patients surviving to > = 3 months post-RT. Of the 2266 3-month survivors (41% NSBM, 59% SM), 1619 (71%) had radiation oncology follow-up, with higher performance status (OR 2.1, 95% CI 1.44-3.05) and younger patients (< 65yo; OR 1.2 95% CI 1.04-1.50) more likely to have follow-up. Median time-to-visit was 59 days (IQR 38-77), with follow-up time distributions significantly different between SM and NSBM (U = 333075, P = 0.01). Of the 3-month survivors, 553 (24%) patients were seen in the UC, with older and white patients less likely to visit the UC (P < 0.05). Median OS for NSBM was longer than the OS for SM patients (22.1 v 17.5 months; HR 0.87 [95% CI 0.78-0.98]). A minority of patients (397, 18%) underwent a subsequent RT course, occurring within 3 months for 183 patients and at a median time of 95 days [IQR 61-130]. Younger age and race were associated with a subsequent RT course (P < 0.05), while performance status and gender were not associated.After RT for bone metastases, most patients had radiation oncology-specific surveillance, which was associated with younger age and improved performance status. Most patients survived to 3 months post-RT, with a substantial minority receiving a second RT course. Patients with NSBM had longer survival and different time-to-follow-up compared to SM, highlighting the need for further clarification on what the optimal follow-up should be for NSBM. Race was a predictor of UC visits, likely reflecting health disparities that require further investigation. These data support radiation oncology specific follow-up after RT, particularly among younger patients and those with higher performance status with specific attention to racial disparities.

Clinical Outcomes of Stereotactic Body Radiation Therapy for Bone and Non-Spine Bone Metastases: A Large Single Institution Experience

<h3>Purpose/Objective(s)</h3> Improved oncologic therapies have expanded the role of stereotactic body radiation therapy (SBRT) for bone metastases; however, the impact of SBRT on local control (LC), progression-free survival (PFS), overall survival (OS) and long-term risks remains poorly understood. We characterized predictive factors associated with clinical outcomes through a large single institution experience. <h3>Materials/Methods</h3> We retrospectively reviewed all patients with bone metastases treated with SBRT at our institution and characterized patient, tumor, and treatment factors and subsequent outcomes. Common treatment indications included synchronous (S) or metachronous (M) oligometastatic cancer, re-irradiation, or radioresistant histology. Common fractionations included 30-35Gy/5F, 9-10Gy/3F, 16-20Gy/1F. Outcomes were assessed on a per patient and per lesion basis using Cox regression to evaluate predictive factors for LC, PFS, and OS. Toxicities were graded by CTCAEv5. <h3>Results</h3> From 2009 to 2020, 434 patients (median age 64, range 19-93, 65% male, 88% Caucasian, ECOG PS 0-1 88%) were treated with SBRT primarily for oligometastatic cancer (82% M, 5% S; 96% with 1-3 lesions) of various origin (39% prostate, 21% breast/lung). 651 lesions (66% spine, 31% non-spine bone, 3% spine/paraspinal) were treated. 96% of lesions had ≥95% PTV covered by 90% of prescription dose (V90) (median 100, range 42-100). Median PTV volume was 41.3cc, and 87% of lesions were < 150cc. 46% lesions were prescribed a biologically equivalent dose (BED) ≥50 (α/β = 10). LC was significantly worse if PTV V90 < 95% (HR 2.06, CI 1.18-3.62, <i>P</i> < 0.05) and improved if prescribed BED≥50 (HR 0.59, CI 0.42-0.83, <i>P</i> < 0.01) on multivariate analysis (MVA). Larger lesions ≥150cc predicted worse LC on univariate analysis (UVA) only (HR 1.80, CI 1.22-2.64, <i>P</i> < 0.005). Improved PFS and OS were associated with better performance status (<i>P</i> < 0.0001) and prostate histology (<i>P</i> < 0.01) on MVA. Metachronous presentation with met-free interval ≥1 year had improved PFS and OS on UVA only (<i>P</i> < 0.001). Common acute toxicities were pain flare (9% vs 12%) and grade 1-2 fatigue (14% vs 19%), among oligometastatic vs re-irradiation lesions, respectively. Late toxicities included treatment-related fracture (1.2%) for oligometastatic lesions and radiation-related myelopathy (2.3%) and nerve pain (1.2%) for re-irradiation/other lesions. <h3>Conclusion</h3> SBRT may be an effective means of improving LC among patients with oligometastatic bone disease if adequate target coverage and a BED≥50 can be achieved, independent of fraction number, and with minimal risk of acute or late toxicity. Prostate histology and performance status were patient factors predictive of PFS and OS. Our experience highlights important factors that can help guide appropriate patient selection and use of SBRT in this unique population.

Phase II Trial of SBRT and Androgen Deprivation for Oligometastases in Prostate Cancer

SBRT-SG 05 is a collaborative (SBRT-SG, GICOR and SEOR) prospective multicenter phase II trial testing SBRT and androgen deprivation therapy (ADT) in oligorecurrent prostate cancer patients.Prostate cancer patients (hormone-sensitive or castration-resistant) in an oligorecurrent stage defined as less than 5 bone or lymph node metastases by Choline PET-CT or/and WB-DWI-MRI, after primary treatment, were assigned to receive ADT and SBRT (Vertebral metastases: 1 × 16-18Gy or 3 × 8-9Gy; lymph node metastases: 3 × 10-11 Gy or 6 × 7,5Gy; non-spinal bone metastases: 1 × 16Gy or 3 × 10Gy). Inclusion criteria included: more than 1 year from primary treatment to biochemical recurrence and PSA doubling time greater than 2 months. A minimum of 24 months of LhRh analogues from the time of the enrollment was required and concomitant treatment with chemotherapy, abiraterone or enzalutamide was not allowed. Oncologic outcomes defined by PCWG3 were evaluated separately for hormone-sensitive and castration-resistant patients, using Kaplan-Meier competing risks, and Cox regression. Toxicity was prospectively evaluated according to CTCAE.v4 criteria.From 07/2014 to 12/2019, 81 patients from 14 Spanish centers were recruited with a total of 117 oligometastases treated, 67 in lymph nodes, 43 in non--spinal bones and 7 in spinal bones. 14 patients were recruited in a castration-resistance status. Median follow-up was 41 months, (range 18 - 72 months). 13 hormone-sensitive (19,4%) and 8 castration-resistant (57,1%) oligorecurrent patients presented distant disease progression. Median distant progression-free survival (DPFS) was 54,2 months (IC95% = 48,2 - 60,3). 18 of the patients who progressed (85,7%) were treated with SBRT for the new lesions, 7 of them presented a subsequent distant progression (38,9%), with a median of second DPFS of 24,4 months (95% CI = 23,7 - 25,2). In the castration resistant subgroup, median DPFS was 33,5 months (range 14,8 - 52,1), 42,9% of them were free from distant disease progression at last follow-up, without the need to start second generation hormonal treatment. Tolerance and toxicity profiles were excellent, none of the patients developed toxicity ≥G3 or symptoms related to local progression of the disease.Combination of SBRT and ADT is a safe treatment approach with favorable clinical outcomes for hormone-sensitive and castration-resistant prostate cancer patients. Validation studies are needed in castration-resistant patients. ClinicalTrials.gov Identifier: NCT02192788.

International Multi-institutional Patterns of Contouring Practice and Clinical Target Volume Recommendations for Stereotactic Body Radiation Therapy for Non-Spine Bone Metastases

Despite the increasing use of stereotactic body radiation therapy for non-spine bone metastases (NSBM), there is no established standard for target delineation. The objective of this study was to provide consensus recommendations on clinical target volume (CTV) delineation based on international expert contours. Eleven cases of NSBM were contoured by 9 international radiation oncologists. For each case, the gross tumor volume was provided on the simulation computed tomography scans with accompanying magnetic resonance imaging. Participants contoured the CTV and completed a clinical survey. Agreement between CTV contours were analyzed with simultaneous truth and performance level estimation using the kappa coefficient and the Dice similarity coefficient (DSC) and summarized to establish contouring recommendations. A direction-dependent analysis was applied to the consensus contours to quantify margins. All CTV contours were completed. Six participants used a single-dose level, whereas 3 used a 2-dose level simultaneous integrated boost (SIB) technique. For the SIB cases, the largest volume receiving a stereotactic body radiation therapy (SBRT) dose was used for contour analysis. There was substantial agreement between contours across cases with a mean kappa of 0.72 (mean sensitivity 0.85, mean specificity 0.97). The mean DSC value was 0.77 (range, 0.67-0.87). Consensus CTV contouring recommendations were (1) an intraosseous CTV margin of 5 to 10 mm should be strongly considered within contiguous bone; (2) an extraosseous margin of 5 to 10 mm should be strongly considered where there is soft tissue disease or cortical bone disruption; (3) CTVs should be manually cropped to respect anatomic barriers to spread (eg, peritoneal cavity, pleura, uninvolved joint space and cortical bone). CTV contouring recommendations for NSBM-SBRT were established based on analysis of international expert consensus contours with a high level of agreement. These principles may provide guidance to treating physicians and inform future study until prospective clinical data can provide further refinement.

Stereotactic body radiotherapy for osseous low alpha\u2013beta resistant metastases for pain relief\u2014SOLAR-P

BackgroundStereotactic Body Radiotherapy (SBRT) has shown effectiveness in treating bone metastases to alleviate pain. The benefit of SBRT may be further harnessed especially when radiating disease from primary malignancies with low alpha–beta ratios in order to maximize the magnitude and durability of pain relief. However, such an approach has not been studied in a prospective trial. We look to assess single-fraction SBRT for painful non-spinal bone metastases from radioresistant primaries.MethodsForty patients will be enrolled on an open label, phase II single arm trial to receive a single fraction of SBRT (15–20 Gray) to all sites of bone metastases requiring treatment for pain relief. Eligible patients will include those with primary malignancies consisting of prostate cancer, breast cancer, renal cell carcinoma, or melanoma. The primary endpoint is pain response at 3 months post-treatment using the Brief Pain Inventory. Secondary endpoints include pain response at 1 month and 6 months post-treatment, toxicity, patient-reported quality of life, re-irradiation or salvage surgery, and local control.DiscussionThis study will evaluate the efficacy of single-fraction SBRT on painful bone metastases from primary cancers with low alpha–beta ratios. These data will be valuable to promote future randomized trials and support clinical implementation.Trial registration Clinicaltrials.gov, NCT04177056. Date of registration: November 26, 2019. https://clinicaltrials.gov/ct2/show/NCT04177056

An international pooled analysis of SBRT outcomes to oligometastatic spine and non-spine bone metastases

PurposeThere is a paucity of data on SBRT to non-spine bone (NSB) lesions compared to spine metastases. We report local recurrence (LR), widespread progression (WSP), and overall survival (OS) for oligometastatic patients treated to bone lesions with SBRT and investigate the hypothesis that outcomes are different between patients with spine and non-spine bone oligometastatic disease. MethodsPatients with oligometastatic disease (≤5 cumulative extracranial metastases) treated with bone SBRT at 6 international institutions from 2007 to 2016 were reviewed. Fine and Gray competing risks and Cox regressions were used to analyze univariable and multivariable relationships between disease/treatment factors and outcomes. ResultsIn total, 288 spine and 233 NSB lesions are reported in 356 patients. Cumulative incidence of LR across all bone lesions was 6.3%, 12.6% and 19.3% at 6 mo, 1 yr and 2 yrs. While univariable analysis suggested inferior LC and OS in spine patients, this did not hold true in multivariable analysis. The final regression model for LR in NSB lesions included PTV ≥ median of 31.8 cc (HR 5.02, p = 0.014) and primary histology, with RCC and NSCLC conferring a 10.8- and 6.5-fold increased risk of LR compared to prostate histology, respectively. The spine LR model included radioresistant histology (HR 2.11, p = 0.0051), PTV Dmin (BED10) ≥ median of 19.1 Gy (HR 0.46, p = 0.0085), and epidural disease (HR 1.99, p = 0.016). ConclusionThis large multi-institutional series reports comparably excellent response to SBRT for a balanced distribution of oligometastatic NSB and spine lesions. Dose escalation for large and/or radioresistant NSB lesions should be explored, given the typical lack of an immediately adjacent dose-limiting critical structure.

Patterns of Palliative Radiotherapy Utilization for Patients With Metastatic Breast Cancer in Harare, Zimbabwe.

PURPOSEIn sub-Saharan Africa, radiotherapy (RT) utilization and delivery patterns have not been extensively studied in patients with metastatic breast cancer.METHODSA retrospective cohort study of female patients with metastatic breast cancer seen at Parirenyatwa Radiotherapy Centre in Zimbabwe from 2014 to 2018 was conducted. Demographics, pathology, staging, and treatment data were abstracted through chart review. Fisher's exact test and chi-squared test of independence were used to compare proportions, and independent two-sample t-tests were used to compare means.RESULTSOf 351 patients with breast cancer, 152 (43%) had metastatic disease, median age 51 years (interquartile range: 43-61 years). Of those with metastatic disease, 30 patients (20%) received radiation to various metastatic sites: 16 spine; three nonspine bone metastases; six whole brain; and five chest wall or supraclavicular. Patients who received radiation were younger (46 v 52 years; P = .019), but did not differ significantly by performance status than those who did not. The most common dose prescription was 30 Gy in 10 fractions (33%). Five (17%) patients had treatment interruption and two (7%) had treatment noncompletion. Province of origin and clinical tumor stage were significant predictors of RT receipt (P = .002; and P = .018, respectively).CONCLUSIONA minority of patients with metastatic breast cancer received RT (20%), and these were likely to be younger, with advanced tumor stage, and resided in provinces where RT is available. Conventional courses were generally prescribed. There is a need to strongly consider palliative RT as an option for patients with metastatic breast cancer and use of hypofractionated courses (e.g. 8 Gy in one fraction) may support this goal.

Multidisciplinary consensus recommendations for the management of non-spine bone metastases: Results of a modified Delphi process in a community-academic partnership.

e24092 Background: Local therapy for bone metastases is becoming increasingly complex, but national guidelines remain limited. We leveraged a community-academic partnership to develop consensus recommendations for multidisciplinary treatment of non-spine bone metastases which are generalizable to diverse practice settings. Methods: We convened a group of 15 physicians (9 radiation oncologists, 2 orthopaedic surgeons, 2 medical oncologists, 1 interventional radiologist, 1 interventional pain specialist) treating bone metastases across 4 institutions from Apr 2020-Feb 2021. We distributed a survey to identify questions warranting consensus development in the treatment of non-spine bone metastases. A literature review was conducted to inform answer statements, and evidence was rated using the Strength of Recommendation Taxonomy. A modified Delphi process was employed to reach consensus defined (a priori) as ³75% of respondents indicating “agree” or “strongly agree”. Results: A total of 16 questions were identified, including indications for multidisciplinary discussion or referral (n=4), appropriate use and duration of RT (n=4), and handling of systemic therapies during RT (n=5). After 2 rounds of modified Delphi process, consensus has been reached on 9 questions (see Table). Strength of Recommendation was rated A (1/9, 11%), B (5/9, 56%), or C (3/9, 33%). Conclusions: Our consensus process provides guidance for management of non-spine bone metastases that expands upon current guidelines. We also highlight areas where prospective trials are needed, including the role of RT prior to stabilization surgery and the selection of patients for ablative treatment. [Table: see text]

Method of computing direction-dependent margins for the development of consensus contouring guidelines

BackgroundClinical target volume (CTV) contouring guidelines are frequently developed through studies in which experts contour the CTV for a representative set of cases for a given treatment site and the consensus CTVs are analyzed to generate margin recommendations. Measures of interobserver variability are used to quantify agreement between experts. In cases where an isotropic margin is not appropriate, however, there is no standard method to compute margins in specified directions that represent possible routes of tumor spread. Moreover, interobserver variability metrics are often measures of volume overlap that do not account for the dependence of disagreement on direction. To aid in the development of consensus contouring guidelines, this study demonstrates a novel method of quantifying CTV margins and interobserver variability in clinician-specified directions.MethodsThe proposed algorithm was applied to 11 cases of non-spine bone metastases to compute the consensus CTV margin in each direction of intraosseous and extraosseous disease. The median over all cases for each route of spread yielded the recommended margins. The disagreement between experts on the CTV margin was quantified by computing the median of the coefficients of variation for intraosseous and extraosseous margins.ResultsThe recommended intraosseous and extraosseous margins were 7.0 mm and 8.0 mm, respectively. The median coefficient of variation quantifying the margin disagreement between experts was 0.59 and 0.48 for intraosseous and extraosseous disease.ConclusionsThe proposed algorithm permits the generation of margin recommendations in relation to adjacent anatomy and quantifies interobserver variability in specified directions. This method can be applied to future consensus CTV contouring studies.

Quality Assurance of Bone SBRT

Stereotactic body radiation therapy (SBRT) is a high-precision radiation therapy technique that enables to deliver a high ablative biological dose in 1 to 5 high dose-fractions despite sparing the high dose of adjacent organs at risk. SBRT has emerged as an alternative to conventional radiation therapy for spinal metastases and has been applied to patients with non-spine bone metastases as well. Since bone SBRT is the technique of high biologically effective dose to the local lesion, quality assurance (QA) of the entire treatment process is an essential for performing SBRT. This report provides QA procedures for performing bone SBRT.