Radiotherapy of bone metastases.

We present the update of the recommendations of the French society of oncological radiotherapy on bone metastases. This is a common treatment in the management of patients with cancer. It is a relatively simple treatment with proven efficacy in reducing pain or managing spinal cord compression. More complex treatments by stereotaxis can be proposed for oligometastatic patients or in case of reirradiation. In this context, increased vigilance should be given to the risks to the spinal cord.

Stereotactic Ablative Radiotherapy for the Management of Spinal Metastases: A Review.

Importance: Rising cancer incidence combined with improvements in systemic and local therapies extending life expectancy are translating into more patients with spinal metastases. This makes the multidisciplinary management of spinal metastases and development of new therapies increasingly important. Spinal metastases may cause significant pain and reduced quality of life and lead to permanent neurological disability if compression of the spinal cord and/or nerve root occurs. Until recently, treatments for spinal metastases were not optimal and provided temporary local control and pain relief. Spinal stereotactic ablative radiotherapy (SABR) is an effective approach associated with an improved therapeutic ratio, with evolving clinical application. Objective: To review the literature of spinal SABR for spinal metastases, discuss a multidisciplinary approach to appropriate patient selection and technical considerations, and summarize current efforts to combine spinal SABR with systemic therapies. Evidence Review: The MEDLINE database was searched to identify articles reporting on spinal SABR to September 30, 2018. Articles including clinical trials, prospective and retrospective studies, systematic reviews, and consensus recommendations were selected for relevance to multidisciplinary management of spinal metastases. Results: Fifty-nine unique publications with 5655 patients who underwent SABR for spinal metastases were included. Four comprehensive frameworks for patient selection were discussed. Spinal SABR was associated with 1-year local control rates of approximately 80% to 90% in the de novo setting, greater than 80% in the postoperative setting, and greater than 65% in the reirradiation setting. The most commonly discussed adverse effect was development of a vertebral compression fracture with variable rates, most commonly reported as approximately 10% to 15%. High-level data on the combination of SABR with modern therapies are still lacking. At present, 19 clinical trials are ongoing, mainly focusing on combined modality therapies, radiotherapy prescription dose, and oligometastic disease. Conclusions and Relevance: These findings suggest that spinal SABR may be an effective treatment option for well-selected patients with spinal metastases, achieving high rates of local tumor control with moderate rates of adverse effects. Optimal management should include review by a multidisciplinary care team.

Stability and survival analysis of elderly patients with osteolytic spinal bone metastases after palliative radiotherapy : Results from a large multicenter cohort.

PURPOSE: This retrospective study aimed to evaluate the stability and fracture rates of osteolytic spinal bone metastases (SBM) in elderly patients following palliative radiotherapy (RT) and to derive prognostic factors for stability and survival. METHODS: A total of 322 patients aged at least 70 years received palliative RT at two major German academic medical centers or at the German Cancer Research Center. Stability assessment was based on the validated Taneichi score prior to RT and at 3 and 6 months after RT. The survival time following RT was assessed, and prognostic factors for stability and survival were analyzed. RESULTS: Prior to RT, 183 patients (57%) exhibited unstable SBM and 68 patients (21%) pathological fractures. At 3 and 6 months after RT, significant recalcification and stabilization were evident in 19% (23/118) and 40% (31/78) of surviving patients, respectively. Only 17 patients (5%) experienced new pathological fractures following RT. Tumor histology was found to significantly influence stabilization rates with only breast cancer patients exhibiting increased stabilization compared to patients with other histologies. The median survival time and 6­month survival rates following RT were 5.4 months (95% confidence interval 4.4-7.2 months) and 48%, respectively. The patients' performance status was found to be the strongest predictor for survival after RT in this patient cohort; further factors demonstrating a significant association with survival were the application of systemic treatment, the number of SBM and the primary tumor histology. To analyze the influence of age on survival after RT, study patients were stratified into 3 age groups (i.e., 70-74 years, 75-79 years, and ≥80 years). The subgroup of patients aged at least 80 years showed a strong trend towards a worse survival time following RT compared to younger patients (i.e., 6­month survival rate 39% vs. 51%; p = 0.06, log-rank test). CONCLUSIONS: Prognostic factors influencing overall survival such as performance status and histology should guide the choice for palliative RT for SBM. Strongly hypofractionated RT regimes may be advisable for most elderly patients considering the overall poor prognosis in order to reduce hospitalization times.

Post-carbon-ion radiotherapy vertebral pathological fractures in upper cervical primary malignant spinal tumors treated by occipito-cervical fusion.

PURPOSE: To describe the characteristic features of post-carbon-ion radiotherapy (CIRT) vertebral pathological fractures (VPFs) in upper cervical primary malignant spinal tumors (PMSTs) treated by occipito-cervical (OC) fusion. METHODS: OC fusion was performed for three consecutive patients with post-CIRT VPFs. The clinical results and imaging findings, including bone single-photon emission computed tomography (SPECT)/CT were prospectively collected. RESULTS: No surgery-related wound complication and surgical site infection were noted. One patient experienced re-fracture and displacement of dens with the loosening of occipital screws and was treated by posterior revision surgery. At the final follow-up, all patients were alive without evidence of disease, and the solid OC fusion was confirmed. Bone SPECT/CT clearly revealed the effect of CIRT on bone turnover in the irradiated field. CONCLUSION: The OC fusion with autologous bone grafts was a reliable option for the treatment of post-CIRT VPCs in the patients with upper cervical PMSTs. In addition, evaluation of the bone turnover at the irradiated field by bone SPECT/CT would help surgeons select an effective plan of care, such as fusion level and postoperative care.

Evaluation of predictive factors of vertebral compression fracture after conventional palliative radiotherapy for spinal metastasis from colorectal cancer.

OBJECTIVE Delayed consequences of spinal radiotherapy (RT), including vertebral compression fracture (VCF), are critical complications. However, the predisposing factors that contribute to VCF after conventional RT are unclear. The aim of this study was to assess the incidence of VCF and to determine the predictors of VCF following conventional spinal RT specific to colorectal cancer (CRC). METHODS The authors retrospectively reviewed 237 spinal segments (147 metastatic and 90 nonmetastatic) in 53 patients with CRC who underwent RT with a median total dose of 30 Gy in 10 fractions between January 2007 and December 2014. The primary end point was the development of a VCF following RT, either de novo VCF or the progression of a baseline VCF. VCFs were assessed using the spinal instability neoplastic score (SINS) criteria. RESULTS Among all 237 spinal segments, 22 VCFs (9.3%) were observed following RT, including 13 de novo and 9 progressive fractures, and the median time to VCF was 4 months. All VCFs developed in metastatic spines. Among 147 metastatic spinal segments, 22 fractures were observed, with a 12-month cumulative incidence of VCF of 14.8%. Results of multivariable analysis indicated sex (p = 0.023) and SINS class II/III (p < 0.001) as risk factors related to development of a VCF in metastatic spinal segments. Among the SINS criteria, a lytic tumor and the presence of a baseline VCF were identified as predictors of VCF in metastatic spinal segments. CONCLUSIONS In osteolytic or mixed lesions that were predominant in spinal metastases of CRC, the incidence of VCF was not negligible, even in patients treated with conventional spinal RT. This was especially evident in patients with spinal metastases with a SINS score ≥ 7. Presence of a baseline VCF after spinal RT is a predictor of VCF development and should be observed carefully.

Patterns of Treatment for Metastatic Pathological Fractures of the Spine: The Efficacy of Each Treatment Modality.

BACKGROUND: Metastatic pathological fractures of the spine are a major problem for cancer patients; however, there is no consensus on treatment strategy. The purpose of this study was to evaluate various treatment options by analyzing their patterns for metastatic pathological fractures of the spine. METHODS: In this study, 54 patients (male:female = 36:18) who were diagnosed with metastatic pathological fractures of spine were recruited. Demographic data, origin of cancer, type of treatment, and results were obtained from electronic medical records. Treatment options were divided into radiotherapy (RT), vertebroplasty (VP) or kyphoplasty (KP), operation (OP), and other treatments. Treatment results were defined as aggravation, no response, fair response, good response, and unknown. The survival time after detection of pathologic fractures was analyzed with the Kaplan-Meier method. RESULTS: The mean age of the patients was 62.3 years. Hepatocellular carcinoma was the most common cancer of primary origin (n = 9), followed by multiple myeloma (n = 8). RT was the most common primary choice of treatment (n = 29, 53.7%), followed by OP (n = 13, 24.1%), and VP or KP (n = 10, 18.5%). Only 13 of 29 RT cases and 7 of 13 OP cases demonstrated a fair or good response. The mean survival time following detection of pathological spinal fractures was 11.1 months for 29 patients, who died during the study period. CONCLUSIONS: RT was the most common primary choice of treatment for metastatic pathological fractures of the spine. However, the response rate was suboptimal. Although OP should be considered for the relief of mechanical back pain or neurologic symptoms, care should be taken in determining the surgical indication. VP or KP could be considered for short-term control of localized pain, although the number of cases was too small to confirm the conclusion. It is difficult to determine the superiority of the treatment modalities, hence, a common guideline for the diagnosis and treatment of metastatic pathological fractures of the spine is required.

The use of vertebral augmentation and external beam radiation therapy in the multimodal management of malignant vertebral compression fractures.

BACKGROUND: Vertebral augmentation (VA) techniques such as vertebroplasty and kyphoplasty are increasingly performed minimally invasive procedures for osteoporotic or malignant compression fractures (MCFs) and involve injection of polymethylmethacrylate (PMMA) cement directly into a compressed vertebral body. OBJECTIVE: This article will evaluate the efficacy of VA in relieving fracture-related pain. We also intend to identify procedural and clinical variables that could potentially influence outcomes in this population. In the subset of patients with cancer who received both external beam radiation therapy (EBRT) and VA, we will assess the impact of the treatment sequence on pain outcomes. STUDY DESIGN: We performed a retrospective analysis of 201 cases of patients with cancer and MCFs who underwent one or more vertebral augmentation procedures at our institution between 2003 and 2009. The majority of cancers represented were multiple myeloma, metastatic lung cancer, and metastatic breast cancer. The primary outcome measure was pain relief, as measured by the Visual Analog Scale and a 4-point pain scale. SETTING: We present an institutional experience at an academic medical center of 201 cases of MCFs. METHODS: We compiled an institutional database of vertebroplasty and kyphoplasty cases using paper and electronic medical records. Our data collection methodology has been previously reported and includes variables such as procedure dates, gender, age, type of malignancy, fracture etiology, history of cancer treatment, type of procedure performed, vertebral level treated, the number of levels treated per procedure, complications, and follow-up information on pain response. The updated dataset incorporates new variables including information on pain medications and standardized questionnaires such as the Visual Analog Scale (VAS) for pain and the Roland Morris Disability Questionnaire (RMDQ). RESULTS: In the 201 cases of MCFs, a total of 316 vertebral levels were treated with either vertebroplasty or kyphoplasty. Follow-up data on pain relief was available for 190 out of 201 cases (95%). Among this subgroup, 168 cases (88%) with MCFs responded. Thirty-nine percent (39%) of the time patients experienced complete pain resolution. In only 4% of cases did patients report worsening of their fracture-related pain post-procedure. There was no difference in pain outcomes with regard to sequencing of EBRT and VA. LIMITATIONS: One of the limitations of our analysis is that it did not evaluate the effect of pain improvement or resolution before and after EBRT alone and on activities of daily living in the majority of patients. However, one of the main goals of this analysis is to address previous limitations. We attempt to standardize outcome measures by using the Visual Analog Scale (VAS) for pain and the Roland Morris Disability Questionnaire (RMDQ). CONCLUSION: A multimodality approach for the management of MCFs includes VA procedures. The majority of patients with MCFs have excellent palliation with this approach. In patients who receive both EBRT and VA, the sequence in which they are given does not affect pain improvement outcomes.

Current role of lateral cervical spine radiograph: a case report.

We report a case showing the classic features of a Hangman's cervical spine fracture following a motor vehicle collision. Because this injury was not diagnosed at ED presentation, this case also illustrates the select subset of trauma patients for whom the almost obsolete lateral cervical spine radiograph remains an important part of the radiographic trauma series.

Painful medial branch neuroma treated with minimally invasive medial branch neurectomy.

STUDY DESIGN: Case report. OBJECTIVE: To report an unusual complication following lumbar facet radiofrequency denervation and describe a successful, minimally invasive treatment of a presumed medial branch neuroma. SUMMARY OF BACKGROUND DATA: Radiofrequency medial branch neurotomy is a common procedure for the treatment of mechanical back pain. Deafferentation injury and neuroma formation is well known and reported following chemical, surgical, and cryoablation neurolysis; however, it is thought to be rare with radiofrequency ablation. When this problem is encountered, treatment options appear to be limited. Further radiofrequency ablations may be ineffective and indeed may cause further injury. METHODS: A 17-year-old male who sustained a traumatic fracture of the right L3-4 facet joint presented with increasing back pain after multiple radiofrequency ablations of the medial branches of the L2 and L3 dorsal rami. The description of the back pain, initially nociceptive in nature, had become progressively neuropathic with clear focal areas of allodynia and hyperesthesia. Further medial branch radiofrequency denervation was found to be ineffective. RESULTS: Diagnostic block of the right medial branch of the L2 dorsal ramus provided the patient with total relief of pain. This was followed by a minimally invasive open surgical ablation of the L2 medial branch neuroma using three-dimensional, fluoroscopy-based image guidance. At 7 months of follow-up, the patient reported complete resolution of pain, discontinuation of all pain medications, and return to all previous physical activities. CONCLUSION: Deafferentation injury is a rare but recognized complication of chemical, surgical, and thermal neuroablation. This case report presents a rare instance of presumed neuroma formation following multiple radiofrequency ablations for the treatment of facet-generated mechanical back pain. Open and minimally invasive medial branch neurectomy resulted in complete resolution of pain and return to baseline function.

Polymethylmethacrylate and radioisotopes in vertebral augmentation: an explanation of underlying principles.

We recently reported a novel concept for combining radioactive isotope technology with polymethylmethacrylate (PMMA) cement used for vertebral augmentation and have advocated that pain physicians become aware of this new concept when treating malignant compression fractures. The use of vertebral augmentation for malignant compression fractures is steadily increasing, and the goal of this novel approach would be to stabilize the fractured vertebral body while also controlling proliferation of the tumor cells in the vertebral body that caused the vertebral fracture. This approach would therefore provide mechanical stabilization of the fractured vertebral body at the same time as direct targeting of the cancer cells causing the fracture. For our analysis, we investigated six specific radioisotopes with regard to physical and biologic properties as they would interact with PMMA and local bone metastatic disease, taking into consideration anatomical, biological and physical characteristics. The radioisotopes investigated include beta emitting (plus and minus) sources, as well as low energy and mid-energy photon sources and are: P-32, Ho-166, Y-90, I-125, F-18, and Tc-99m. We review the advantages and disadvantages of each radioisotope. In addition, this paper serves to provide pain physicians with a basic background of the biologic principles (Biologically Effective Dose) and statistical modeling (Monte Carlo method) used in that analysis. We also review the potential complications when using radioactive sources in a clinical setting. Understanding the methodologies employed in determining isotope selection empowers the practitioner by fostering understanding of this presently theoretical treatment option. We believe that embedding radioisotopes in PMMA is merely a first step in the road of local treatment for symptomatic local lesions in the setting of systemic disease.

DEGRO practice guidelines for palliative radiotherapy of metastatic breast cancer: bone metastases and metastatic spinal cord compression (MSCC).

PURPOSE: To provide practice guidelines and clinical recommendations on preferred standard palliative radiation therapy of bone metastases as well as metastatic spinal cord compression (MSCC) for metastatic breast cancer patients. METHODS: The breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials. The literature search encompassed the period 1995-2008 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were "breast cancer", "bone metastasis", "osseous metastasis", "metastatic spinal cord compression" as well as "radiotherapy" and "radiation therapy". Clinical recommendations were formulated based on the panel's interpretation of the level of evidence referring to the criteria of evidence-based medicine. RESULTS: Different therapeutic goals (pain relief, local tumor control, prevention or improvement of motor deficits, stabilization of the spine or other bones) require complex approaches considering individual factors (i.e., life expectancy, tumor progression at other sites). Best results are achieved by close interdisciplinary cooperation minimizing the interval between diagnosis and onset of treatment. Most important criteria for prognosis and choice of treatment (mostly combined multimodal therapy) are neurologic status at diagnosis of MSCC, time course of duration and progression of the neurologic symptoms. Radiation therapy is effective and regarded as treatment of choice for MSCC with or without motor deficits and/or bone metastases, which do not need immediate surgical intervention. It may be used either postoperatively or as primary treatment in case of inoperability. An optimal dose fractionation schedule or optimal standard dose for treatment of bone metastases has not been established. With regard to different therapeutic goals, different dose concepts and fractionation schedules, single- versus multifraction palliative radiation therapy (1 x 8, 5 x 4, 10 x 3, 15 x 2.5, 20 x 2 Gy), should be adapted individually. CONCLUSION: Bone metastases as well as MSCC should be managed in an interdisciplinary approach mostly as combined-modality treatment according to the specific clinical situation. The present practice guidelines offer criteria and recommendations for different radiooncologic treatment schedules based on the best available levels of evidence. Preferred technique, targeting and different dose schedules are described in detail.

Delayed L2 vertebrae split fracture following kyphoplasty.

Kyphoplasty is an accepted therapeutic modality for the treatment of painful osteoporotic vertebral compression fractures. Complication rates are reported between 1% and 3% for osteoporotic fractures. Most previously reported complications, however, have occurred perioperatively. In this article, we report a case in which balloon kyphoplasty was performed as described by manufacturer guidelines. Four weeks after a successful kyphoplasty, the patient presented with a painful split vertebral fracture with anterior deformity at the same level where the kyphoplasty was initially performed. A recurrent fracture at the same level of a previous successful kyphoplasty may be considered in the differential diagnosis of a patient who presents with new pain at a similar level.

Fratura toracolombar tipo explosão: comparação do tratamento conservador em pacientes com e sem fratura do arco vertebral posterior / Thoracolumbar burst fracture: comparing conservative treatment in patients with and without fracture of the posterior vertebral arch

OBJETIVO: Comparar clínica e radiologicamente os resultados a longo prazo do tratamento conservador da fratura explosão toracolombar, em pacientes com e sem fratura do arco vertebral posterior, com o propósito de avaliar eventuais diferenças na evolução destes dois tipos de lesão. MÉTODOS: Foram avaliados, retrospectivamente, os prontuários e exames de imagem (radiografias e tomografias computadorizadas) de 25 pacientes sem déficit neurológico, com fratura toracolombar tipo explosão tratados não cirurgicamente e comparados o grau de progressão da cifose entre os casos com fratura da lâmina (grupo 1) e sem fratura posterior (grupo 2). Desses, 13 pacientes foram submetidos à avaliação comparativa por meio da escala visual analógica de dor (VAS), da escala de dor e trabalho de Denis e do questionário de qualidade de vida SF-36. RESULTADOS: Foram analisados 25 pacientes (36 por cento do grupo A e 74 por cento do grupo B) com tempo médio de seguimento de 111,64 meses. Não houve diferença em relação ao grau de progressão da cifose durante o seguimento entre os grupos A e B (5,22º x 4,63º - p = 0,650). Dos 13 pacientes analisados funcionalmente, 46 por cento eram do grupo A e 54 por cento do grupo B. Nesta avaliação, apesar da VAS pior (1,83 x 5,00 - p = 0,015) nos pacientes sem fratura posterior (grupo B), não houve diferença em relação à escala de Denis (4,00 x 5,71 - p > 0,05) e SF-36 (98,60 x 90,83 - p = 0,168) entre os dois grupos. CONCLUSÃO: A fratura do arco posterior, isoladamente, parece não ser indicativo de instabilidade ou de mau prognóstico nas fraturas toracolombares tipo explosão.

OBJECTIVE: To make a clinical and radiological comparison of long term results of the conservative treatment of thoracolumbar burst fractures, in patients with and without fracture in the posterior vertebral arch, in order to assess possible differences in the evolution of the two types of lesion. METHODS: A retrospective analysis was made of the clinical records and imaging exams (X-rays CT scans) of 25 patients without neurological deficit with thoracolumbar burst fractures treated without surgery, and a comparison was made of the degree of progression of kyphosis between the cases with fracture of the lamina (Group 1) and those without posterior fracture (Group 2). 13 of these patients were submitted to comparative evaluation using the visual analogical scale of pain (VAS), the Denis pain and work scale, and the life quality questionnaire SF-36. RESULTS: 25 patients were analyzed (36 percent in group A and 74 percent in group B) with mean follow-up of 111.64 months. There was no difference in the degree of kyphosis progression during follow-up between groups A and B (5.22º x 4.63º - p = 0.650). Of the 13 patients functionally analyzed, 46 percent were from group A and 54 percent from group B. In this assessment, despite the worse VAS (1.83 x 5.00 - p = 0.015) in patients without posterior fracture (Group B), there was no difference in the Denis scale (4.00 x 5.71 - p > 0.05 ) and SF-36 (98.60 x 90.83 - p = 0.168) between the two groups. CONCLUSION: Taken separately, the posterior arch fracture does not seem to be an indicator of instability or of poor prognosis in thoracolumbar burst fractures.

Palliative radiotherapy in patients with multiple myeloma.

PURPOSE: To analyse the therapeutic effect of palliative radiation therapy (RT) in multiple myeloma (MM) patients with bone lesions and soft tissue formations, to compare the therapeutic efficacy of two different RT regimens, the effect of RT on basic disease parameters, and its impact on survival in MM patients. PATIENTS AND METHODS: 162 patients with MM were diagnosed and followed for a 10-year period (1994-2004). Eighty-seven (53.7%) of them with myeloma bone disease (MBD) underwent palliative RT with two different regimens. The effect of RT on MBD and its complications was assessed. Patients with RT were compared in 10 parameters before and after RT. Survival was compared between the irradiated and non irradiated groups and also between patients treated with two different RT regimens, using Kaplan-Meier method and log-rank test. RESULTS: RT was applied in 92.1% of the patients with vertebral fractures, in 90.9% of the patients with non-vertebral fractures, and in 94.1% of the patients with extramedullary tumor formations. In 89.6% of the patients complete or partial pain palliation was achieved and in 58.6% resolution of neurologic symptoms occurred. The levels of hemoglobin (Hb), white blood cell (WBC) and platelet counts (PLT), bone marrow infiltration, serum calcium (Ca), creatinine, albumin, CRP, LDH, beta2-microglobulin did not change significantly before and after RT. Median survival of patients on RT was 32 months (range 30-34) vs. 33 months (range 28-36) for patients without RT (p>0.05). Median survival was 32 months (range 27-37) for patients on 2x8 Gy. vs. 34 months (range 25-39) for those on 5x4 Gy (p>0.05). CONCLUSION: RT is a very effective method in bone pain palliation in vertebral and non-vertebral fractures and reduction of extramedullary formations, but does not influence the survival of patients with MM.

Long-term effects of localized spinal radiation therapy on vertebral fractures and focal lesions appearance in patients with multiple myeloma.

The occurrence of new vertebral fractures and focal marrow lesions was determined and compared in irradiated and nonirradiated vertebrae of 12 patients with multiple myeloma (MM), prospectively followed using magnetic resonance imaging (MRI) of the thoraco-lumbar spine after localized spinal radiation therapy. During follow-up (mean 35 months), fractures appeared in 5% of irradiated vertebrae and in 20% of nonirradiated vertebrae: new focal lesions appeared in 4% of irradiated vertebrae and in 27% of nonirradiated vertebrae. This study demonstrates a beneficial long-term effect of localized radiation therapy, consisting of a reduced incidence of vertebral fractures and focal marrow lesions in irradiated vertebrae.

Pedicle fixation: an adjuvant for the treatment of thoracolumbar metastases.

For a long time, radiotherapy was considered as the best treatment for spinal metastases. However, radiotherapy alone could not resolve the problem of pathological fracture which is an important complication of spinal metastases. In this paper, we introduce pedicle fixation system as an adjuvant to radiotherapy to treat eight patients with thoracolumbar metastases. The result was encouraging that all the patients achieved spinal stabilisation and all but one had immediate postoperative relief of back pain. The operation time was short and none of the patients required a blood transfusion. Tissue diagnosis was possible through this approach.