Treatment Of Painful Bone Metastases Research Articles

Kemik Metastazlarının Tedavisinde Radyofarmasötiklerin Rolü

Cancer, having quite high morbidity and mortality rates, has become a significant public health problem in recent years, and it is the second leading cause of death after heart disease in the world. Metastases are one of the most serious complications of cancer, and bone metastases are detected in 2/3 of metastatic cancer cases. General therapy approaches in bone metastases can be classified as surgery, bisphosphonates therapy, radiotherapy, and radionuclide therapy. Radionuclide therapy using alpha and beta emitting radionuclides is more selective and effective than other local and systemic treatment methods, and this feature provide several advantages over existing therapeutic methods. Radionuclide therapy used in bone metastasis for reducing the pain, killing tumor cells, prolonging life span, and improving quality of life.
 
 In recent years, alpha-emitting radiopharmaceuticals [such as Radium-223 (Ra-223) chloride] and beta-emitting radiopharmaceuticals [such as Strontium-89 (Sr-89) chloride, Lutetium-177 (Lu-177) labeled Ethylenediamine Tetra Methylene Phosphonic Acid (EDTMP), Samarium-153 (Sm-153) labeled EDTMP] are introduced in the clinic for especially the treatment of painful bone metastases and on the other hand new radiopharmaceutical development studies also continue intensively, like Actinium-225 labeled prostate-specific membrane antigen-617 (Ac-225-PSMA). Many studies have proven that using radiopharmaceuticals in the therapy of bone metastases improves the patient's general health, reduces pain and the risk of pathological fractures, and increases survival. 
 
 This review presents an overview of radionuclide therapy used in bone metastases. In this context, general information about the radiopharmaceuticals is given, and the importance of the use of radiopharmaceuticals in bone metastases therapy is explained with experimental and clinical studies examples.

PO-1581 Can MR-guided HIFU replace palliative radiotherapy in the treatment of painful bone metastases?

PO-1581 Can MR-guided HIFU replace palliative radiotherapy in the treatment of painful bone metastases?

Dosimetric Comparison of Different Radionuclides Used in Metastatic Bone Disease Treatment.

This study aimed to determine the critical organ doses in 223Ra, 89Sr, 153Sm, and 32P treatments via dosimetry using the phantoms. The OpenDose was used to calculate S values (mGy MBq-1s-1) for bone surface, red bone marrow, urinary bladder wall, testes, ovaries, uterus, and kidneys using male (ICRP110AM) and female (ICRP110AF) phantoms. The cortical thoracic spine was modeled as metastasis. Moreover, the absorbed doses were computed via MIRD formalism according to the activities of 3.3, 148, 2220, and 370 MBq for ICRP110AM and 4.015, 148, 2701, and 370 MBq for ICRP110AF in 223Ra, 89Sr, 153Sm, and 32P treatments, respectively. Whilst the maximum bone surface doses were found as 1.22E+02 and 8.51E+01 mGy at 32P treatment, the minimum bone surface doses were calculated as 8.42E-02 and 8.26E-02 mGy at 223Ra. In terms of the comparison of red bone marrow, urinary bladder wall, and kidney doses, 153Sm and 89Sr treatments showed maximum doses of 2.45E-03, 1.50E-03, 3.23E-07, 5.45E-06, 1.20E-01, 1.49E-01 mGy and the minimum doses with 3.46E-05, 1.99E-05, 6.33E-09, 8.77E-09, 1.19E-04, 1.15E-04 mGy, respectively. The maximum testes and ovaries-uterus doses were found as 6.17E-08, 7.40E-06, 3.46E-07 mGy in 153Sm treatment, and minimum testes and ovaries doses as 1.70E-09, 1.34E-07 mGy in 223Ra. The minimum uterus dose with 7.03E-09 mGy was determined in 89Sr treatment. It is observed that 223Ra produces low critical organ doses in the treatment of painful bone metastasis. Among the beta-emitting radionuclides, 89Sr stands out by showing optimal dosimetric results.

FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases (FAST-01): Protocol for the First Prospective Feasibility Study.

In preclinical studies, FLASH therapy, in which radiation delivered at ultrahigh dose rates of ≥40 Gy per second, has been shown to cause less injury to normal tissues than radiotherapy delivered at conventional dose rates. This paper describes the protocol for the first-in-human clinical investigation of proton FLASH therapy. FAST-01 is a prospective, single-center trial designed to assess the workflow feasibility, toxicity, and efficacy of FLASH therapy for the treatment of painful bone metastases in the extremities. Following informed consent, 10 subjects aged ≥18 years with up to 3 painful bone metastases in the extremities (excluding the feet, hands, and wrists) will be enrolled. A treatment field selected from a predefined library of plans with fixed field sizes (from 7.5 cm × 7.5 cm up to 7.5 cm × 20 cm) will be used for treatment. Subjects will receive 8 Gy of radiation in a single fraction-a well-established palliative regimen evaluated in prior investigations using conventional dose rate photon radiotherapy. A FLASH-enabled Varian ProBeam proton therapy unit will be used to deliver treatment to the target volume at a dose rate of ≥40 Gy per second, using the plateau (transmission) portion of the proton beam. After treatment, subjects will be assessed for pain response as well as any adverse effects of FLASH radiation. The primary end points include assessing the workflow feasibility and toxicity of FLASH treatment. The secondary end point is pain response at the treated site(s), as measured by patient-reported pain scores, the use of pain medication, and any flare in bone pain after treatment. The results will be compared to those reported historically for conventional dose rate photon radiotherapy, using the same radiation dose and fractionation. FAST-01 opened to enrollment on November 3, 2020. Initial results are expected to be published in 2022. The results of this investigation will contribute to further developing and optimizing the FLASH-enabled ProBeam proton therapy system workflow. The pain response and toxicity data acquired in our study will provide a greater understanding of FLASH treatment effects on tumor responses and normal tissue toxicities, and they will inform future FLASH trial designs. : ClinicalTrials.gov NCT04592887; http://clinicaltrials.gov/ct2/show/NCT04592887. DERR1-10.2196/41812.

The Burden of Metastatic Cancer-Induced Bone Pain: A Narrative Review.

Bone pain is one of the most common forms of pain reported by cancer patients with metastatic disease. We conducted a review of oncology literature to further understand the epidemiology of and treatment approaches for metastatic cancer–induced bone pain and the effect of treatment of painful bone metastases on the patient’s quality of life. Two-thirds of patients with advanced, metastatic, or terminal cancer worldwide experience pain. Cancer pain due to bone metastases is the most common form of pain in patients with advanced disease and has been shown to significantly reduce patients’ quality of life. Treatment options for cancer pain due to bone metastases include nonsteroidal anti-inflammatory drugs, palliative radiation, bisphosphonates, denosumab, and opioids. Therapies including palliative radiation and opioids have strong evidence supporting their efficacy treating cancer pain due to bone metastases; other therapies, like bisphosphonates and denosumab, do not. There is sufficient evidence that patients who experience pain relief after radiation therapy have improved quality of life; however, a substantial proportion are nonresponders. For those still requiring pain management, even with available analgesics, many patients are undertreated for cancer pain due to bone metastases, indicating an unmet need. The studies in this review were not designed to determine why cancer pain due to bone metastases was undertreated. Studies specifically addressing cancer pain due to bone metastases, rather than general cancer pain, are limited. Additional research is needed to determine patient preferences and physician attitudes regarding choice of analgesic for moderate to severe cancer pain due to bone metastases.

Concurrent capecitabine with external beam radiotherapy versus radiotherapy alone in painful bone metastasis of breast cancer origin

BackgroundIn breast cancer, painful bone metastases are common. Local radiotherapy is the standard treatment of painful bone metastases. Pain control and overall response rateswere low in radiotherapy alone.The objectives of this study were to compare the safety and efficacy of external beam radiotherapy with concurrent capecitabine vs. external beam radiotherapy alone in pain control of painful bone metastases in breast cancer patients. Materials and methodsEighty-four patients with painful bone metastases from breast cancer participated in this prospective study. We randomized the patients into two groups: group A treated with radiotherapy 30 Gy in 10 fractions and group B treated with capecitabine 825 mg/m2 every 12 hrs. concurrently with the same radiotherapy dose. ResultsThere was no statistically significant difference between the two groups regarding early treatment toxicity. Most of the toxicity was gastrointestinal (diarrhea and nausea) and mild (grade I or II). The median pain score decreased from week one, and there was a marked response at week4. The difference in median pain score between both groups was statistically significant with p-value = 0.045. The median analgesic score in both groups was statistically significant with a p-value = 0.032 at week 12. A complete response to pain at week 4 was 19% and 42.9% in groups A and B, respectively. ConclusionConcurrent chemoradiation in painful bone metastases from breast cancer origin was tolerable and safe; it had a higher overall response rate and pain palliation than radiotherapy alone.

Does kV Image Guidance for Bone Metastases Improve Pain Control?

Purpose/ObjectivesDespite its widespread availability, the use of kilovoltage (kV) image guidance is often related to factors such as perceived adequacy of clinical patient setup and individual practice patterns. We sought to determine whether kV image guidance in the treatment of painful bone metastases would improve therapeutic efficacy.Materials/MethodsUnder an Institutional Review Board approved protocol, hospital records of 164 patients having received radiation therapy to 257 individual painful osseous metastases were retrospectively reviewed. Marginal logistic regression analyses using the generalized estimating equation (GEE) approach were used to investigate potential associations between pain reduction and several patient, disease, and treatment related variables. Correlation of kV image guidance with pain reduction was analyzed by univariate and multivariate GEE logistic regression analysis.ResultsMedian time to pain reduction was 3 days (range 0~109 days) from the start of radiation therapy. Pain reduction ≥ 50% was noted in 196 (77%) metastatic lesions with 136 (53%) demonstrating complete pain relief. Patients with metastatic lesions from non-small cell lung cancer experienced less pain relief (p = 0.007). Disease extension outside of bone was a negative predictor for pain reduction (p = 0.02). On univariate and multivariate logistic regression, kV image guidance demonstrated a statistically significant correlation with improved pain control in cases involving treatment of the lower extremities (p = 0.03) and those with fewer treatment fractions (p = 0.01), particularly in the setting of extra-osseous disease extension (p = 0.003).ConclusionsKilovoltage image guidance in the treatment of painful bone metastases may offer greater pain control through improved patient setup, particularly for patients with tumors of the lower extremities, extraosseous disease extension, and fewer treatment fractions.

Efficacy and safety of magnetic resonance-guided focused ultrasound for the treatment of painful bone metastases: a systematic review and meta-analysis

ObjectiveTo report the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of painful bone metastases through a systematic review and meta-analysis of pain scores before and after MRgFUS treatment and post-treatment adverse events.Materials and methodsA comprehensive literature search of PubMed and Embase databases was performed for studies evaluating the efficacy and/or safety of MRgFUS. The mean difference of pain scores (10-point visual analogue scale or numerical rating scale) between baseline and 1-month/3-month pain scores was collected and analyzed in a pooled meta-analysis. Post-treatment adverse events based on the Common Terminology Criteria for Adverse Events (CTCAE) grading were recorded and the pooled prevalence was calculated.ResultsA total of 33 studies published between 2007 and 2019 were collected, resulting in a total sample size of 1082 patients. The majority of the studies were prospective with a reported follow-up period of 3 months. The pooled proportion of patients that achieved pain relief from MRgFUS (complete response or partial response [≥ 2-point improvement of pain score]) was 79% (95% CI 73–83%). The pooled 1-month and 3-month mean difference in pain score were − 3.8 (95% CI − 4.3; − 3.3) and − 4.4 (95% CI − 5.0; − 3.7), respectively. The overall rate of high-grade (CTCAE grade 3 or higher) and low-grade (CTCAE grade 2 or lower) MRgFUS-related adverse events were 0.9% and 5.9%, respectively.ConclusionMRgFUS is an effective procedure that is able to provide significant pain palliation for patients with symptomatic bone metastases with a favorable safety profile.

Computed Tomography‒Guided Microwave Ablation Combined with Osteoplasty for the Treatment of Bone Metastases: A Multicenter Clinical Study

PurposeTo evaluate the efficacy and safety of combined microwave ablation (MWA) and osteoplasty as a palliative therapy for painful bone metastases. Materials and MethodsAs an extension of a previous limited single-center study, a retrospective review was conducted for 147 patients (77 male, 70 female) with painful bone metastases who underwent MWA combined with osteoplasty. In total, 102 (69.4%), 41 (27.9%), and 4 (2.7%) patients had spinal metastases, extraspinal metastases, and both, respectively. Treatment efficacy was determined by comparing visual analog scale (VAS) scores, daily morphine equivalent opioid consumption, and Oswestry disability index (ODI) scores before treatment and during the follow-up period (mean follow-up, 9.8 months; range 3–16). ResultsThe mean VAS score significantly declined from 6.4 ± 2.3 before treatment to 3.2 ± 2.1, 1.9 ± 1.6, 1.8 ± 1.6, 1.8 ± 1.6, and 1.9 ± 1.6 at 24 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after treatment, respectively (P < .01). Furthermore, the mean daily morphine equivalent opioid consumption was significantly reduced from 81.5 ± 32.8 mg before treatment to 40.0 ± 20.6, 32.4 ± 10.2, 26.4 ± 10.0, 21.5 ± 8.3, and 19.3 ± 7.4 mg. The mean ODI score also declined after treatment (P < .0001). Major complications occurred in 4 of 147 patients, with 1 pathologic fracture, 1 nerve injury, and 2 mild skin infections. Minor cement leakages were observed at 69 sites (32.8%). ConclusionsMWA combined with osteoplasty is an effective and safe treatment for painful bone metastases.

Real-Time Magnetic Resonance Guided Focused Ultrasound for Painful Bone Metastases.

Bones are one of the most common sites of cancer metastasis, which usually causes pain and impairs quality of life. Radiation therapy combined with opioids is the standard treatment for painful bone metastases. This treatment achieves effective pain control in 60-74% of patients, but limited treatment choices with limited benefits are available for recurrent or residual painful bone metastases after radiotherapy. More than 40% of patients still experience moderate to severe bone pain after reirradiation. Magnetic resonance-guided focused ultrasound (MRgFUS) combines high-intensity focused ultrasound, which achieves thermal ablation of bone metastases and subsequent pain reduction, with real-time magnetic resonance (MR) thermometry to monitor the temperature of anatomic MR images, with an accuracy of 1 °C, spatial resolution of 1 mm, and temporal resolution within 3 s. As well as being increasingly used clinically for controlling metastatic bone pain, the use of MRgFUS for other diseases has also been tested. However, the use of MR software as a thermometer is the only technique available to verify the accuracy of the software and assure energy delivery. Here, we describe an efficient method of quality assurance we developed for thermal detection and energy delivery before each MRgFUS treatment and also propose a modified workflow to expedite the treatment course as well as to reduce patients' pain during the procedure.

Cost-effectiveness analysis of magnetic resonance-guided focused ultrasound ablation for palliation of refractory painful bone metastases.

The aim of this study was to determine if magnetic resonance-guided focused ultrasound (MRgFUS) is cost-effective compared with medication, for refractory pain from bone metastases in the United States. We constructed a Markov state transition model using TreeAge Pro software (TreeAge Software, Inc., Williamstown, MA, USA) to model costs, outcomes, and the cost-effectiveness of a treatment strategy using MRgFUS for palliative treatment of painful bone metastases compared with a Medication Only strategy (Figure 1). Model transition state probabilities, costs (in 2018 US$), and effectiveness data (quality-adjusted life-years [QALYs]) were derived from available literature, local expert opinion, and reimbursement patterns at two U.S. tertiary academic medical centers actively performing MRgFUS. Costs and QALYs, discounted at three percent per year, were accumulated each month over a 24-month time horizon. One-way and probabilistic sensitivity analyses were performed. In the base-case analysis, the MRgFUS treatment strategy costs an additional $11,863 over the 2-year time horizon to accumulate additional 0.22 QALYs, equal to a $54,160/QALY ICER, thus making MRgFUS the preferred strategy. One-way sensitivity analyses demonstrate that for the base-case analysis, the crossover point at which Medication Only would instead become the preferred strategy is $23,341 per treatment. Probabilistic sensitivity analyses demonstrate that 67 percent of model iterations supported the conclusion of the base case. Our model demonstrates that MRgFUS is cost-effective compared with Medication Only for palliation of painful bone metastases for patients with medically refractory metastatic bone pain across a range of sensitivity analyses.

Radiofrequency Ablation for the Palliative Treatment of Bone Metastases: Outcomes from the Multicenter OsteoCool Tumor Ablation Post-Market Study (OPuS One Study) in 100 Patients

PurposeTo evaluate the effectiveness of radiofrequency (RF) ablation as measured by change in worst pain score from baseline to 3 mo after RF ablation for the palliative treatment of painful bone metastases. Materials and MethodsOne hundred patients (mean age, 64.6 y) underwent RF ablation for metastatic bone disease and were followed up to 6 mo. Subjects’ pain and quality of life were measured before RF ablation and postoperatively by using the Brief Pain Index and European Quality of Life questionnaires. Opioid agent use and device-, procedure-, and/or therapy-related adverse events (AEs) were collected. ResultsEighty-seven patients were treated for tumors involving the thoracolumbar spine and 13 for tumors located in the pelvis and/or sacrum. All ablations were technically successful, and 97% were followed by cementoplasty. Mean worst pain score decreased from 8.2 ± 1.7 at baseline to 3.5 ± 3.2 at 6 mo (n = 22; P < 0.0001 for all visits). Subjects experienced significant improvement for all visits in average pain (P < .0001), pain interference (P < .0001), and quality of life (P < .003). Four AEs were reported, of which 2 resulted in hospitalization for pneumonia and respiratory failure. All 30 deaths reported during the study were attributed to the underlying malignancy and not related to the study procedure. ConclusionsResults from this study show rapid (within 3 d) and statistically significant pain improvement with sustained long-term relief through 6 mo in patients treated with RF ablation for metastatic bone disease.

Image-guided Cryotherapy for Musculoskeletal Tumors

This article represents a review of the use of image-guided cryotherapy in the treatment of musculoskeletal tumor lesions. Cryotherapy is able to induce a lethal effect on cancer cells through direct and indirect mechanisms. In this manuscript, we combined our experience with that of other authors who have published on this topic in order to provide indications on when to use cryotherapy in musculoskeletal oncology. Image-Guided percutaneous cryotherapy is a therapeutic method now widely accepted in the treatment of patients with musculoskeletal tumors. It can be used both for palliative treatments of metastatic bone lesions and for the curative treatment of benign bone tumors, such as osteoid osteoma or osteoblastoma. In the treatment of bone metastases, cryotherapy plays a major role in alleviating or resolving disease-related pain, but it has also been demonstrated that it can have a role in local disease control. In recent years, the use of cryotherapy has also expanded for the treatment of both benign and malignant soft tissue tumors. Percutaneous cryotherapy can be considered a safe and effective technique in the treatment of benign and malignant musculoskeletal tumors. Cryotherapy can be considered the first option in benign tumor lesions, such as osteoid osteoma, and a valid alternative to radiofrequency ablation. In the treatment of painful bone metastases, it must be considered secondarily to other standard treatments (radiotherapy, bisphosphonate therapy, and chemotherapy) when they are no longer effective in controlling the disease or when they cannot be repeated (for example, radiotherapy).

Ultrasound-Guided Focused Ultrasound Treatment for Painful Bone Metastases: A Pilot Study

Focused ultrasound (FUS) for palliation of bone metastases has typically been performed under magnetic resonance guidance. To address limitations of this approach, this pilot study evaluated a stand-alone, portable FUS device guided by diagnostic ultrasound alone (ultrasound [US]-guided FUS). Nine patients were treated; safety and efficacy were assessed for 10 d after the procedure, and medical charts were evaluated to assess durability of pain response. The procedure was safe and tolerable, with four patients reporting minor skin-related irritations. Average pain score decreased from 6.9 at baseline to 3.2 at day 10; analgesic use on average also decreased from baseline to day 10. Six patients had durable pain relief as assessed after the follow-up period. Our study provides evidence that US-guided FUS is a safe, tolerable and versatile procedure. It appears to be effective in achieving durable pain response in patients with painful bone metastases. Further research is required to refine the technology and optimize its efficacy.

A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET)

BackgroundBone metastases represent an important source of morbidity in cancer patients, mostly due to severe pain. Radiotherapy is an established symptomatic treatment for painful bone metastases, however, when conventional techniques are used, the effectiveness is moderate. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, could potentially be more effective and less toxic.MethodsThis is a phase III, randomized-controlled, single-blind, multicenter study evaluating the response rate of antalgic radiotherapy for painful bone metastases and the acute toxicity associated with this treatment. A total of 126 patients will be randomly assigned to receive either the standard schedule of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy or a single fraction of 20.0 Gy delivered through SBRT. Primary endpoint is pain response at the treated site at 1 month after radiotherapy. Secondary endpoints are pain flare at 24–48-72 h after radiotherapy, duration of pain response, re-irradiation need, acute toxicity, late toxicity, quality of life and subsequent serious skeletal events. In a supplementary analysis, patient-compliance for a paper-and-pencil questionnaire will be compared with an electronic mode.DiscussionIf a dose-escalated approach within the context of single fraction stereotactic body radiotherapy could improve the pain response to radiotherapy and minimize acute toxicity, this would have an immediate impact on the quality of life for a large number of patients with advanced cancer. Potential disadvantages of this technique include increased pain flare or a higher incidence of radiation-induced fractures.Trial registrationThe Ethics committee of the GZA Hospitals (B099201732915) approved this study on September 4th 2018. Trial registered on Clinicaltrials.gov (NCT03831243) on February 5th 2019.

Palliative Radiation Therapy for Bone Metastases in Neuroendocrine Neoplasms

PurposeBone metastases are reported in 10% to 12% of patients with neuroendocrine neoplasms (NENs) and can lead to pain and skeletal-related events (SREs), resulting in diminished quality of life and functional status. In other solid tumors with bone metastases, radiation therapy (RT) is an established treatment approach for SREs, yet few data are available in NENs historically considered to be radioresistant. We hypothesize that RT is effective for pain and other SREs in NENs and aimed to delineate any differences in pain palliation and time until progression of pain between different fractionation and dosing schedules of RT. Methods and MaterialsWe retrospectively reviewed 686 records of patients with NENs treated at the institution between 2011 and 2018 and identified 28 (4.1%) patients treated with RT for 61 cases of SREs. The primary endpoint was change in patient reported pain scores after RT. ResultsAll 28 patients experienced bone pain. Nineteen sites were treated with a single fraction (doses of 800-1800 cGy) and 42 sites with fractionated regimens (doses of 900-3750 cGy over 3-15 fractions). In 55 of 61 cases (90%), patients experienced improvement in pain after RT. The median time to recurrence or progression of pain was 3.5 months. Significant differences were found between primary site and change in performance status (P = .024), sex, and reported magnitude of pain score decrease after RT (P = .025). There were no differences in the time to the progression of pain, change in performance status, and degree of improvement in pain based on age, chemotherapy received during RT, or radiation site. Outcomes were similar for patients who received single-fraction versus fractionated regimens (P = .545) and between those receiving palliative versus ablative RT regimens (P = .812). ConclusionsAlthough the majority of cases in this NEN cohort benefited from RT, additional studies on the use of RT in the treatment of painful bone metastases are warranted.

MR-guided high intensity focused ultrasound (MRgHIFU) ablation of bone lesions: Impact of the ultrasound focusing on the thermal curves and of dissection needles interposition on the ultrasound field

Objective To evaluate the impact of the ultrasound (US) focusing on the thermal curves in an in vitro (bone and cement) and in vivo experiment [1] . To compare these results with the acoustic and thermal simulation results [2] , [3] . To evaluate the US field distortion secondary to dissection needles. Material and methods MRgHIFU sonications were performed on a bone marrow (F = 1 MHz, P = 25 W during 90 s), on the ilium of a pig (in vivo) (F = 1 MHz, P = 79 W during 40 s) and a specimen of cement (F = 2.7 MHz, P = 20 W during 45 s). Focusing was superficial (at the periosteum or on the cement), deep (in the marrow or behind the cement) or intermediate (cortical bone). An acoustic and thermal simulation (k-wave) was performed using the same model of bone marrow with two values of bone acoustic absorption coefficient (α = 4.7 et 9.9 dB/cm) and compared with the MRI thermometry. For spinal and pelvic lesions, a dissection may be necessary to protect nerves during thermal ablation [4] : therefore, the impact of dissection needles (22 to 13-gauge) on the US field was evaluated. Results A vaster and higher periosteal heating was observed with deep sonication ( Fig. 1 ). The lateral and vertical heating tended to appear with a delay, which can be explained by thermal inertia. These results were best reproduced with the simulation for α=4.7 dB/cm. Simulation with α = 9.9 dB/cm showed a much higher periosteal heating and different thermal curves. Cement and in vivo thermal curves were similar to the bone marrow results. No US field distortion was observed with 22 to 18-gauge needles. Conclusion For the treatment of painful bone metastases, deep focusing may be the most efficient. Simulations can reproduce the in vitro results. However, simulation results depend on tumoral bone α which remains difficult to measure. For spinal or pelvic lesions thermal ablation requiring a protection of neural structures [5] , dissection needles may be placed in the HIFU cone without any consequence at the condition that the liquid injected does not spread in front the US.

An assessment of bone-seeking radionuclides for palliation of metastatic bone pain in a vertebral model.

Bone-seeking radiopharmaceuticals have the main role in the treatment of painful bone metastases. The aim of this study was to dosimetrically compare radiopharmaceuticals in use for bone pain palliation therapy and bone scan. The MCNPX code was used to simulate the radiation transport in a vertebral phantom. Absorbed fractions were calculated for monoenergetic electrons, photons and alpha particles. S values were obtained for radionuclides 32P, 33P, 89Sr, 90Y, 99mTc, 117mSn, 153Sm, 166Ho, 169Er, 177Lu, 186Re, 188Re, 223Ra, 224Ra and their progenies for target regions including the active marrow and the bone endosteum. The results demonstrated the dependence of dosimetric parameters on the source or target size, particle energy and location of the source. The electron emitters including 33P, 117mSn, 169Er and 177Lu and 223Ra as an α-emitter gave the lower absorbed dose to the active marrow. These radionuclides gave the highest values of the Relative Advantage Factor (RAF). According to the results,33P, 117mSn, 169Er, 177Lu and 223Ra have fewer side effects on the active marrow than other investigated radionuclides. Therefore, these radionuclides may be a better choice for use in palliative radiotherapy.

Strontium-89 Chloride Delivery for Painful Bone Metastasis in Patients with History of Previous Radiation

Re-irradiation of previously irradiated site must be done with careful consideration to minimizing dose to organs at risk. In particular, re-irradiation of the spine carries significant morbidity due to risk of myelitis. Strontium-89 chloride (Sr-89) is widely used for treatment of painful bone metastasis. The purpose of this study is to evaluate pain response and safety of Sr-89 administration for painful bone metastasis in the setting of prior radiation. After institutional review board approval, records of patients who received Sr-89 injection for painful bone metastasis in previously irradiated sites were retrospectively reviewed. Patients with follow-up of less than 1 month were excluded from analysis. Efficacy of pain control was evaluated with the verbal rating scale (VRS), documentation of the analgesic dose employing the World Health Organization (WHO) pain relief ladder. Adverse events were measured using CTCAE v4.0. Twenty-three patients met study inclusion criteria, of which 12 were male and 11 were female. Median age at treatment was 69 years (50-83). Primary sites were lung (n=11), prostate (n=3), breast (n=2), uterine cervix (n=2), kidney (n=1), and other (n=4). Median follow-up was 8 (1-49) months. Twelve patients treated with SR-89 had prior history of palliative radiation therapy for bone metastasis. The remainder had received radiation for non-bony metastasis as follows: concurrent chemo-radiotherapy (CCRT) for lung cancer (n=7), post-operative radiotherapy to regional lymph nodes of breast cancer (n=1), pre-operative CCRT for rectal cancer (n=1), radical CCRT for cervical cancer (n=1), and radiotherapy to tumor bed for recurrent prostate cancer (n=1). Prior to administration of Sr-89, the VRS grade of 0/1/2/3 was n=1/5/12/5, respectively. Analgesic score 0/1/2/3/4/5/6 was n=3/9/2/4/3/1/1, respectively. After administration of Sr-89, VRS grade didn’t change in 3 patients, and improved in 20; 17 occurred after 1 month, 2 after 2 months, and 1 after 3 months. Analgesic score didn’t change in 15 but improved in 8 patients; 4 after 1 month, 2 after 2 months, 2 after 3 months. In two patients neither the VRS nor the analgesic score improved and in two patients the VRS improved but the analgesic score increased, hence difficult to evaluate efficacy of SR-89. This made the response rate of evaluable patients 90.1%. Flare phenomenon was observed in 3 patients, but all were controlled with analgesic and improved within one week. No grade 2 or worse adverse events was observed. Administration of strontium-89 chloride to patients with painful bone metastasis at previously irradiated sites is an effective and safe treatment options for palliation of symptoms at the end of life.

Percutaneous image-guided ablation of bone metastases: local tumor control in oligometastatic patients

Introduction: Percutaneous image-guided cryo- (CA) and radiofrequency- (RFA) ablations have been widely used in the treatment of painful bone metastases (BM). However, paucity of data is available for the performance of these treatments when used with a curative intent. The aim of this study is to investigate the local progression free-survival (LPFS) after radical percutaneous image-guided ablation of BM in oligometastatic patients, and to identify predictive factors associated with local tumor progression.Materials and Methods: This is a retrospective review of all patients who underwent percutaneous image-guided CA or RFA of BM with a radical intent between 2007 and 2018.Results: Forty-six patients with a total of forty-nine BM underwent percutaneous image-guided CA (N = 37; 75,5%) or RFA (N = 12; 24,5%). Primary malignancies included thyroid (N = 11, 22.5%), breast (N = 21; 42.9%), lung (N = 8; 16.3%) and other (N = 9; 18,3%) cancers. Additional consolidation was performed after ablation in 20.4% cases (N = 10). Mean follow-up was 34.1 ± 22 months. Local progression at the treated site was observed in 28.5% cases (N = 14); 1- and 2-year LPFS was 76.8% and 71.7%, respectively. Size of BM (>2 cm) predicted local tumor progression (p = .002).Conclusions: Percutaneous image-guided locoregional therapies used in the radical treatment of BM in oligometastatic patients demonstrate significant rates of LPFS providing the size of BM ≤2 cm.