3D bioprinted osteosarcoma model for experimental boron neutron capture therapy (BNCT) applications: Preliminary assessment.

Osteosarcoma is the most frequently primary malignant bone tumor characterized by infiltrative growth responsible for relapses and metastases. Treatment options are limited, and a new therapeutic option is required. Boron neutron capture therapy (BNCT) is an experimental alternative radiotherapy able to kill infiltrative tumor cells spearing surrounding healthy tissues. BNCT studies are performed on 2D in vitro models that are not able to reproduce pathological tumor tissue organization or on in vivo animal models that are expensive, time-consuming and must follow the 3R's principles. A 3D in vitro model is a solution to better recapitulate the complexity of solid tumors meanwhile limiting the animal's use. Objective of this study is to optimize the technical assessment for developing a 3D in vitro osteosarcoma model as a platform for BNCT studies: printing protocol, biomaterial selection, cell density, and crosslinking process. The best parameters that allow a fully colonized 3D bioprinted construct by rat osteosarcoma cell line UMR-106 are 6 × 106 cells/ml of hydrogel and 1% CaCl2 as a crosslinking agent. The proposed model could be an alternative or a parallel approach to 2D in vitro culture and in vivo animal models for BNCT experimental study.

Evaluation of the Clinical Utility of the Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP): A Case-Based Pilot Assessment.

PURPOSE: The Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP) provides patient-specific survival predictions and evidence-based recommendations to guide multidisciplinary management for symptomatic bone metastases. We assessed the clinical utility of the BMETS-DSP through a pilot prepost design in a simulated clinical environment. METHODS: Ten Radiation Oncology physicians reviewed 55 patient cases at two time points: without and then with the use of BMETS-DSP. Assessment included 12-month survival estimate, confidence in and likelihood of sharing estimates with patients, and recommendations for open surgery, systemic therapy, hospice referral, and radiotherapy (RT) regimen. Paired statistics compared pre- versus post-DSP outcomes. Reported statistical significance is P < .05. RESULTS: Pre- versus post-DSP, overestimation of true minus estimated survival time was significantly reduced (mean difference -2.1 [standard deviation 4.1] v -1 month [standard deviation 3.5]). Prediction accuracy was significantly improved at cut points of < 3 (72 v 79%), ≤ 6 (64 v 71%), and ≥ 12 months (70 v 81%). Median ratings of confidence in and likelihood of sharing prognosis significantly increased. Significantly greater concordance was seen in matching use of 1-fraction RT with the true survival < 3 months (70 v 76%) and < 10-fraction RT with the true survival < 12 months (55 v 62%) and appropriate use of open surgery (47% v 53%), without significant changes in selection of hospice referral or systemic therapy. CONCLUSION: This pilot study demonstrates that BMETS-DSP significantly improved physician survival estimation accuracy, prognostic confidence, likelihood of sharing prognosis, and use of prognosis-appropriate RT regimens in the care of symptomatic bone metastases, supporting future multi-institutional validation of the platform.

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

BACKGROUND: The 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. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: Eighty 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.

Association of the Oncology Care Model With Value-Based Changes in Use of Radiation Therapy.

PURPOSE: Radiation utilization for breast cancer and metastatic bone disease varies in modality, fractionation, and cost, despite evidence demonstrating equal effectiveness and consensus recommendations such as Choosing Wisely that advocate for higher value care. We assessed whether the Oncology Care Model (OCM), an alternative payment model for practices providing chemotherapy to patients with cancer, affected the overall use and value of radiation therapy in terms of Choosing Wisely recommendations. METHODS AND MATERIALS: We used Centers for Medicare & Medicaid Services administrative data to identify beneficiaries enrolled in traditional fee-for-service Medicare who initiated chemotherapy episodes at OCM and propensity-matched comparison practices. Difference-in-difference (DID) analyses evaluated the effect of OCM on overall use of postoperative radiation for breast cancer, use of intensity modulated radiation therapy and hypofractionation for breast cancer, and fractionation patterns for treatment of metastatic bone disease from breast or prostate cancer. We performed additional analyses stratified by the presence or absence of a radiation oncologist in the practice. RESULTS: Among 27,859 postoperative breast cancer episodes, OCM had no effect on overall use of radiation therapy after breast surgery (DID percentage point difference = 0.4%; 90% confidence interval [CI], -1.7%, 2.4%) or on use of intensity modulated radiation therapy in this setting (DID = -0.6; 90% CI, -3.1, 2.0). Among 19,366 metastatic bone disease episodes, OCM had no effect on fractionation patterns for palliation of bone metastases (DID for ≤10 fractions = -1.1%; 90% CI, -2.6%, 0.4% and DID for single fraction = -0.2%; 90% CI, -1.9%, 1.6%). Results were similar for practices with and without a radiation oncologist. We did not evaluate the effect of OCM on hypofractionated radiation after breast-conserving surgery owing to evidence of differential baseline trends. CONCLUSIONS: OCM had no effect on use of radiation therapy after breast-conserving surgery for breast cancer or on fractionation patterns for metastatic bone disease. Future payment models directly focused on radiation oncology providers may be better poised to improve the value of radiation oncology care.

Bone marrow dosimetry for 141Ce-EDTMP as a potential bone pain palliation complex: A Monte Carlo study.

Due to favorable physical properties of 141Ce radionuclide [Eßmax = 434.6 keV (70.5%) and 580.0 keV (29.5%), Eγ = 145.4 keV, and physical half-life = 32.5 day], a complex including this radionuclide could be a good candidate for palliative therapy of metastatic bone patients and an alternative to 89SrCl2 as a FDA-approved radiopharmaceutical. Because the bone marrow absorbed dose is a limiting factor in the palliative therapy of bone metastases, this study conducted to calculate the bone marrow absorbed dose of 141Ce-EDTMP complex and compare it with the 89SrCl2 using Monte Carlo simulation. In this study, the GATE Monte Carlo toolkit and two human bone models including vertebra and femur bones were used for simulations. The vertebra and femur bone marrow absorbed dose from 141Ce-EDTMP were 29.1 and 4.3 mGy/MBq, respectively. Moreover, the vertebra and femur bone marrow absorbed dose from 89SrCl2 were 109.2 and 16.3 mGy/MBq, respectively. Bone-to-bone marrow absorbed dose ratio in the vertebra for 141Ce-EDTMP and 89SrCl2 was 34.2 and 11.6, respectively, whereas, this ratio in the femur was 23.8 and 7.5, respectively. Owing to the high bone-to-bone marrow absorbed dose ratio and lower bone marrow absorbed dose than 89SrCl2, 141Ce-EDTMP could be a promising new complex for palliative therapy of patients with bone metastasis.

Diffusion kurtosis imaging assessment of the response to radiotherapy in a VX2 bone tumor model: an animal study.

BACKGROUND: Neoadjuvant radiotherapy plays a vital role in the treatment of malignant bone tumors, and non-invasive imaging methods are needed to evaluate the response to treatment. PURPOSE: To assess the value of diffusion kurtosis imaging (DKI) for monitoring early response to radiotherapy in malignant bone tumors. MATERIAL AND METHODS: Treatment response was evaluated in a rabbit VX2 bone tumor model (n = 35) using magnetic resonance imaging (MRI), DKI, and histopathologic examinations. Subjects were divided into three groups: pre-treatment, post-treatment, and control groups. The post-treatment group was subclassified into good response and poor response groups according to the results of histopathologic examination. Apparent diffusion coefficient (ADC) and DKI parameters (mean diffusion coefficient [MD] and mean kurtosis [MK]) were recorded. The relationship between ADC, DKI parameters, and histopathologic changes after radiotherapy was determined using Pearson's correlation coefficient. The diagnostic performance of these parameters was assessed using receiver operating characteristic analysis. RESULTS: MD in the good response group was higher after treatment than before treatment (P < 0.001) and higher than that in the poor response group (P = 0.009). MD was highly correlated with tumor cell density and apoptosis rate (r = -0.771, P < 0.001 and r = 0.625, P < 0.001, respectively). MD was superior to other parameters for determining the curative effect of radiotherapy, with a sensitivity of 75.0%, specificity of 100.0%, and area under the curve of 0.917 (P < 0.001). CONCLUSION: The correlations between MD, tumor cell density, and apoptosis suggest that MD could be useful for assessing the early response to radiotherapy in rabbit VX2 malignant bone tumors.

A qualitative research study in Japan investigating patients' experience with metastatic castration-resistant prostate cancer: from diagnosis to decision for Ra-223 treatment.

Aim: This qualitative study aimed to reveal symptoms and impacts among bone metastatic castration-resistant prostate cancer (or mCRPC) Japanese patients, prior to Radium-223 (Ra-223) treatment. Materials & Methods: Twenty-three mCRPC patients designated to receive Ra-223 and three treating physicians (Ra-223 prescribers) in Japan, were interviewed. All interview data were assessed for concept frequency, themes and saturation. Results: Forty-five percent of the patients (mean age: 75.8 years) were symptomatic at the time of enrollment. Interviews with all patients revealed 47 mCRPC symptoms, including back pain and bone-specific pain, and 45 life impacts, including worry about disease progression and the impact on daily, physical activities. Conclusion: The symptoms and impacts of living with mCRPC and the associated burden of bone metastasis and skeletal-related symptoms are varied and are important considerations for treatment.

Lay abstract Aim: This study looked at symptoms and impacts among patients with a type of prostate cancer called metastatic castration-resistant prostate cancer. This cancer has spread to other parts of the body including patients' bones. Patients' prostate-specific antigen levels continue to rise despite surgical or medical treatment and their doctors decided the next best treatment is Radium-223 (Ra-223), a radiopharmaceutical therapy. Materials & methods: Twenty-three metastatic castration-resistant prostate cancer patients designated to receive Ra-223 and three treating physicians (Ra-223 prescribers) in Japan, were interviewed. All interview data were assessed for the number of times some words or themes are mentioned by the patients. Results: Ten of the 23 patients (average age of 76 years) had symptoms when the study started. Interviewed patients talked about symptoms including back pain and pain in their bones, and how their cancer caused them to worry about their physical activities and disease progression. Conclusion: The symptoms impact on patients' daily living and the burden of bone metastasis and bone-related symptoms are varied and are important considerations for treatment.

COVID-19 and radiotherapy: potential new strategies for patients management with hypofractionation and telemedicine.

COVID-19 disease is one of the biggest public health challenges in Italy and global healthcare facilities, including radiotherapy departments, faced an unprecedented emergency. Cancer patients are at higher risk of COVID-19 infection because of their immunosuppressive state caused by both tumor itself and anticancer therapy adopted. In this setting, the radiation therapy clinical decision-making process has been partly reconsidered; thus, to reduce treatment duration and minimize infection risk during a pandemic, hypofractionated regimens have been revised. Moreover, telemedicine shows its helpfulness in the radiotherapy field, and patients get the supportive care they need minimizing their access to hospitals. This review aims to point out the importance of hypofractionated RT and telemedicine in cancer patient management in the COVID-19 era.

Pain response and quality of life assessment in patients with moderate/severe neuropathic pain due to bone metastasis undergoing treatment with palliative radiotherapy and tapentadol: A prospective multicentre pilot study.

INTRODUCTION: To assess pain response rate (RR) and quality of life (QoL), in patients with moderate/severe neuropathic pain (NP) due to bone metastasis (BM) undergoing palliative 3D radiotherapy plus tapentadol. METHODS: We conducted a prospective multicentre pilot study. Patients were assessed before radiotherapy using the validated questionnaire (Douleur Neuropathique en 4 questions). Response to radiotherapy (8 Gy-30 Gy/1-10fr) at one and two months was assessed according the International Bone Metastases Consensus criteria. INCLUSION CRITERIA: radiological evidence of BM, NP according to DN4 (cut-off score ≥ 4), no spinal cord compression, worst pain score ≥ 5/10. Nonparametric Mann-Whitney U test compared changes in QoL among response groups. RESULTS: Seventeen patients (13 men, 4 woman), median age 67 years (42-81), were included. Pre-treatment median pain severity was 7.5 (5-10). Median dose of tapentadol administered before radiotherapy was 100 mg/24 h (100-300 mg). Overall RR 1 month after radiotherapy was 10/16 = 62.5%: 3/16 (18.8%) achieving a complete response (CR) and 7/16 (43.8%) a partial response (PR). Overall RR 2 months after RT was 5/10 (50%): 10% a CR and 40% a PR. ITT RR for this study at 1 and 2 months was 10/17 = 59% and 5/17 = 29%, respectively. Patients responding to radiotherapy had significant improvement in EORTC QLQ-C30 emotional functioning (EF) (p = 0.025) and fatigue symptom scale scores (p = 0.035) one month after radiotherapy. Painful site symptom QLQ-BM22 scores improved 2 months after radiotherapy (p = 0.024). CONCLUSIONS: Palliative radiotherapy plus tapentadol shows an acceptable pain response and QoL improvement especially regarding EF, fatigue and painful site symptom scales in patients with moderate/severe NP due to BM. Therefore, it could be an alternative to manage NP in daily practice.

Assessment of RBE-Weighted Dose Models for Carbon Ion Therapy Toward Modernization of Clinical Practice at HIT: In Vitro, in Vivo, and in Patients.

PURPOSE: Present-day treatment planning in carbon ion therapy is conducted with assumptions for a limited number of tissue types and models for effective dose. Here, we comprehensively assess relative biological effectiveness (RBE) in carbon ion therapy and associated models toward the modernization of current clinical practice in effective dose calculation. METHODS: Using 2 human (A549, H460) and 2 mouse (B16, Renca) tumor cell lines, clonogenic cell survival assay was performed for examination of changes in RBE along the full range of clinical-like spread-out Bragg peak (SOBP) fields. Prediction power of the local effect model (LEM1 and LEM4) and the modified microdosimetric kinetic model (mMKM) was assessed. Experimentation and analysis were carried out in the frame of a multidimensional end point study for clinically relevant ranges of physical dose (D), dose-averaged linear energy transfer (LETd), and base-line photon radio-sensitivity (α/ß)x. Additionally, predictions were compared against previously reported RBE measurements in vivo and surveyed in patient cases. RESULTS: RBE model prediction performance varied among the investigated perspectives, with mMKM prediction exhibiting superior agreement with measurements both in vitro and in vivo across the 3 investigated end points. LEM1 and LEM4 performed their best in the highest LET conditions but yielded overestimations and underestimations in low/midrange LET conditions, respectively, as demonstrated by comparison with measurements. Additionally, the analysis of patient treatment plans revealed substantial variability across the investigated models (±20%-30% uncertainty), largely dependent on the selected model and absolute values for input tissue parameters αx and ßx. CONCLUSION: RBE dependencies in vitro, in vivo, and in silico were investigated with respect to various clinically relevant end points in the context of tumor-specific tissue radio-sensitivity assignment and accurate RBE modeling. Discovered model trends and performances advocate upgrading current treatment planning schemes in carbon ion therapy and call for verification via clinical outcome analysis with large patient cohorts.

Accounting for Range Uncertainties in the Optimization of Combined Proton-Photon Treatments Via Stochastic Optimization.

PURPOSE: Proton treatment slots are a limited resource. Combined proton-photon treatments, in which most fractions are delivered with photons and only a few with protons, may represent a practical solution to optimize the allocation of proton resources over the patient population. We demonstrate how a limited number of proton fractions can be optimally used in multimodality treatments and address the issue of the robustness of combined treatments against proton range uncertainties. METHODS AND MATERIALS: Combined proton-photon treatments are planned by simultaneously optimizing intensity modulated radiation therapy and proton therapy plans while accounting for the fractionation effect through the biologically effective dose model. The method was investigated for different tumor sites (a spinal metastasis, a sacral chordoma, and an atypical meningioma) in which organs at risk (OARs) were located within or near the tumor. Stochastic optimization was applied to mitigate range uncertainties. RESULTS: In optimal combinations, proton and photon fractions deliver similar doses to OARs overlaying the target volume to protect these dose-limiting normal tissues through fractionation. Meanwhile, parts of the tumor are hypofractionated with protons. Thus, the total dose delivered with photons is reduced compared with simple combinations in which each modality delivers the prescribed dose per fraction to the target volume. The benefit of optimal combinations persists when range errors are accounted for via stochastic optimization. CONCLUSIONS: Limited proton resources are optimally used in combined treatments if parts of the tumor are hypofractionated with protons and near-uniform fractionation is maintained in serial OARs. Proton range uncertainties can be efficiently accounted for through stochastic optimization and are not an obstacle for clinical application.

Physician Practice Variability in the Use of Extended-Fraction Radiation Therapy for Bone Metastases: Are We Choosing Wisely?

PURPOSE: Routine use of extended-fraction (> 10 fractions) radiation therapy (RT) for palliation of bone metastases is recognized as a low-value intervention by the American Society for Radiation Oncology. We examined contemporary practice patterns of, and physician characteristics associated with extended-fraction RT use. MATERIALS AND METHODS: We conducted a retrospective cohort study using Medicare fee-for-service data. We included patients who underwent 2- or 3-dimensional external-beam RT for bone metastases between January 1, 2016, and December 31, 2018. Physicians treating > 10 patients over the study period were analyzed for their individual practice. Hierarchic logistic regression modeling was used to identify patient- and physician-level factors associated with extended-fraction RT use. RESULTS: A total of 12,221 patients (median age, 75.6 years; 40.9% women, 87.6% white) were included. The rate of extended-fraction RT was 23.4%. A total of 1,432 physicians treated any patient. Among the 382 physicians treating > 10 patients, 127 (33.2%) used extended-fraction RT > 30% (consensus threshold). Physician factors associated with decreased odds of extended-fraction RT were years since medical school graduation (≤ 10 years and 11-20 years v ≥ 31 years: adjusted odds ratio [aOR], 0.32 [95% CI, 0.20 to 0.51] and 0.64 [95% CI, 0.44 to 0.93]) and practicing in the Northeast or Midwest versus the South (aOR, 0.36 [95% CI, 0.22 to 0.58] and 0.48 [95% CI, 0.31 to 0.74]). Physicians treating > 20 patients (v 11-14 patients) over the study period had increased odds of delivering extended-fraction RT (aOR, 1.53 [95% CI, 1.10 to 2.12]). CONCLUSION: In this study, almost one fourth of patients received extended-fraction RT, and one third of physicians had an extended-fraction RT use rate of > 30%. Personalized feedback of performance data, clinical pathways and peer review, and updated reimbursement models are potential mechanisms to address this low-value care.

Improving the accuracy of converting dose to medium to dose to water algorithms in small megavoltage photon fields in dose to medium based treatment planning systems.

PURPOSE: To present a formalism to improve the accuracy of converting absorbed dose to medium in medium (Dm) to absorbed dose to water in medium (Dw) in small megavoltage photon fields for different human tissues in Dm-based treatment planning systems (TPS). METHODS: Eight kinds of real human tissues were simulated to convert Dm to Dw. Four kinds of virtual water media were deliberately designed to analyze source of deviations from the conventional Bragg-Gray theory. Mass electronic stopping powers were calculated using the ESTAR code. The phase-space data was generated by the EGSnrc/BEAMnrc Monte Carlo code. The dose deposition was calculated with the EGSnrc/DOSRZnrc code. Electron fluence spectra calculated with EGSnrc/FLURZnrc code were utilized to analyze fluence perturbations and determine fluence intensity (Φw,mint) and fluence spectral shape (Φw,mS) correction factors. RESULTS: Large conversion errors of Dw using Bragg-Gray theory were observed, such as 19.65% ± 9.58% (average value ± standard deviation, type A) for inflated lung (ICRU). Fluence perturbations could be exacerbated by severe charged particle disequilibrium conditions. These deviations were caused by the synergy between tissues' different mean excitation energies and smaller mass densities compared to those of water. Adding Φw,mint and Φw,mS correction factors to modify Bragg-Gray theory could greatly reduce Dw conversion errors, within 1.00% for all tissues studied. CONCLUSIONS: The current clinically used Dw conversion algorithm in commercial Dm-based TPS isn't appropriate for some human tissues in small field dosimetry. Correction factors should be exploited to improve the accuracy.

SUPR-3D: A randomized phase iii trial comparing simple unplanned palliative radiotherapy versus 3d conformal radiotherapy for patients with bone metastases: study protocol.

BACKGROUND: Bone metastases in the lower spine and pelvis are effectively palliated with radiotherapy (RT), though this can come with side effects such as radiation induced nausea and vomiting (RINV). We hypothesize that high rates of RINV occur in part because of the widespread use of inexpensive simple unplanned palliative radiotherapy (SUPR), over more complex and resource intensive 3D conformal RT, such as volumetric modulated arc therapy (VMAT). METHODS: This is a randomized, multi-centre phase III trial of SUPR versus VMAT. We will accrue 250 patients to assess the difference in patient-reported RINV. This study is powered to detect a difference in quality of life between patients treated with VMAT vs. SUPR. DISCUSSION: This trial will determine if VMAT reduces early toxicity compared to SUPR and may provide justification for this more resource-intensive and costly form of RT. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03694015 . Date of registration: October 3, 2018.

Comparison between Targeted Radionuclide Therapy of Bone Metastases Based on ß-Emitting and α-Emitting Radionuclides.

INTRODUCTION: The α- and ß-emitter radionuclides are used for palliative treatment of bone metastasis. Our objective was to compare the dosimetric parameters of radionuclides used in bone pain palliation therapy. METHODS: Monte Carlo code, MCNPX, was used to simulate radiation transport. Dosimetric calculations were performed for monoenergetic electrons with energies of 0.1-3 MeV, α-particles with energies of 3-10 MeV, and several radionuclides 32P, 89Sr, 153Sm, 177Lu, 223Ra, and its progeny. The simulated phantom consisted of bone marrow, an endosteal layer, bone, and soft tissue. Source tissues included bone marrow, endosteal layer, and bone. Absorbed fractions and specific absorbed fractions were calculated for target regions. Absorbed doses were calculated for investigated radionuclides. RESULTS: The obtained results demonstrated that the dosimetric parameters vary depending on the source or target size, particle energy, and location of the source. The ß-emitter radionuclides were able to penetrate the bone marrow region, whereas the α-emitter radionuclides gave a higher and localized dose to the bone and endosteal layer in comparison. CONCLUSION: 223Ra and 177Lu have fewer side effects on the bone marrow, and they may be a better choice for use in bone pain palliation radiotherapy.

Treatment outcomes of stereotactic ablative radiation therapy for non-spinal bone metastases: focus on response assessment and treatment indication.

OBJECTIVE: To report treatment outcomes of stereotactic ablative radiation therapy (SABR) for non-spinal bone metastases in a single institution, and to compare assessments of Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 and the University of Texas MD Anderson Cancer Center (MDA) criteria. METHODS: From July 2011 to January 2017, 33 patients with 38 non-spinal bone metastatic lesions were treated using SABR. Treatment intent was categorized as follows: single metastasis or oligo-metastases; oligo-progression; and dominant areas of progression. Tumor responses were evaluated according to the RECIST and MDA criteria. Local control (LC) was defined as lesions that were not classified as progressive disease on both criteria. RESULTS: The median follow-up period was 10.4 months (range, 2.5-47.4). Both 1- and 2 year LC rates were 94.2 %. The median overall survival (OS) was 20.2 months, and the median progression-free survival (PFS) was 6.9 months. Treatment intent was a significant factor for OS in multivariate analysis. The 1 year OS rates for single metastasis or oligo-metastasis, for oligo-progression, and for dominant areas of progression were 84.2%, 66.7%, and 0.0%, respectively ( p < 0.001). Overall response rate was 86.8 % according to MDA criteria, and 75.7 % according to RECIST criteria. When using MDA criteria, there appeared to be significant associations both between response and PFS (median 7.6 months for responders vs 2.5 months for non-responders; p = 0.036) and between response and OS. In contrast, when using RECIST criteria, the associations were significant neither between response and PFS (median 5.8 months for responders vs 9.3 months for non-responders; p = 0.522) nor between response and OS (25.7 months for responders vs 18.5 months for non-responders; p = 0.811). CONCLUSION: SABR for non-spinal bone metastases demonstrated high LC rates with acceptable toxicity. The MDA criteria demonstrated advantages in predicting survival outcomes. ADVANCES IN KNOWLEDGE: SABR for non-spinal bone metastases is a promising treatment option to achieve good local control. The MDA criteria, which is a newly proposed response evaluation criteria for bone metastases, has advantages in predicting survival outcomes compared to other established criteria.

Persistent Use of Extended Fractionation Palliative Radiotherapy for Medicare Beneficiaries With Metastatic Breast Cancer, 2011 to 2014.

INTRODUCTION: With no evidence to support extended radiation courses for the palliation of bone metastases, multiple guidelines were issued discouraging its use. We assessed contemporary use and cost of prolonged palliative radiotherapy in Medicare beneficiaries with bone metastases from breast cancer. METHODS: We conducted a retrospective, longitudinal study of palliative radiotherapy use among fee-for-service Medicare beneficiaries with bone metastasis from breast cancer who underwent palliative radiotherapy during 2011 to 2014. Patients were categorized according to the number of days (fractions) on which they received palliative radiotherapy: 1, 2 to 10, 11 to 19, or 20 to 30. We examined the association of clinical, demographic, and provider characteristics with the use of extended (≥11 fractions) or very extended (≥20 fractions) fractionation with logistic regression models. We also compared the cost of different fractionation schemes from the payer perspective. RESULTS: Of the 7547 patients in the sample (mean age, 71 y), 3084 (40.8%) received extended fractionation. The proportion of patients receiving 11 to 19 (34.7% in 2011 and 28.1% in 2014, trend P<0.001) and 20 to 30 treatments (10.3% in 2011 to 9.0% in 2014, trend P=0.07) decreased modestly over time. Patients with comorbidities were less likely to undergo extended fractionation (34.4% for ≥3 comorbidities vs. 44.9% for 0 comorbidities; adjusted odds ratio 0.67 [95% confidence interval, 0.58-0.76]). Patients treated at free-standing practices were more likely to undergo extended fractionation (47.9%) compared with those treated at hospital-based practices (37.3%, P<0.001; adjusted odds ratio, 1.49 [95% confidence interval, 1.35-1.65]). The mean cost of treatment varied from $633 (SD $240) for single-fraction treatment, to $3566 (SD $1349) for 11 to 19 fractions, to $6597 (SD $2893) for 20 to 30 fractions. CONCLUSION: The use of prolonged courses of palliative radiotherapy among Medicare beneficiaries with breast cancer remained high in 2011 to 2014. The association between free-standing facility status and use of extended fractionation suggests that provider financial incentives may impact choice of treatment.

Assessment of the radiation absorbed dose produced by 177Lu-iPSMA, 225Ac-iPSMA and 223RaCl2 to prostate cancer cell nuclei in a bone microenvironment model.

This research aimed to assess the radiation absorbed dose produced by 177Lu-iPSMA (177Lu-prostate specific membrane antigen inhibitor), 225Ac-iPSMA and 223RaCl2 to prostate cancer cell nuclei in a simplified model of bone by using an experimental in-vitro prostate cancer LNCaP cell biokinetic study and Monte Carlo simulation with the MCNPX code. Results showed that 225Ac-iPSMA releases a nine hundred-fold radiation dose greater than 177Lu-iPSMA and 14 times more than 223RaCl2 per unit of activity retained in bone. 225Ac-iPSMA could be the best option for treatment of bone metastases in prostate cancer.

Early response assessment of re-ossification after palliative conventional radiotherapy for vertebral bone metastases.

BACKGROUND: To evaluate the therapeutic outcomes in patients with bone metastases receiving radiotherapy (RT), it is important to use objective radiological response criteria. The aim of this study was to investigate the changes in pain and re-ossification after RT for painful vertebral bone metastases without paralysis by malignant spinal cord compression. METHODS: The participants included 55 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. Bone modifying agents (BMAs) were administered in all patients. Follow-up assessments were done just before the start of RT and at 1, 2, 3, 4, and 6 months after RT. Radiological responses of irradiated vertebrae by RT were assessed by computed tomography (CT) using MD Anderson response classification criteria (MDA criteria) and the pain response was assessed by Numeric Rating Scale (NRS). Response was classified as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD). RESULTS: The rates of CR were 2%, 7%, 20%, 30%, and 56% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were 15%, 49%, 77%, 91%, and 91% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were significantly higher in patients with breast cancer than in patients with lung cancer (p = 0.043). At one month, there was an association between the NRS and radiological response assessed by MDA criteria. There was a significant trend that, with a better response, there were more patients without pain (p = 0.021). CONCLUSIONS: Under BMAs administration, successful RT for vertebral bone metastases decreased pain and caused re-ossification. The MD Anderson criteria could be useful for assessment of radiological responses of irradiated vertebrae.