RESUMO
BACKGROUND: Bone metastases can compromise the integrity of the spinal canal and cause epidural spinal cord compression (ESCC). The Spinal Instability Neoplastic Score (SINS) was developed in order to evaluate spinal instability due to a neoplastic process. The SINS has reached wide acceptance among clinicans but its prognostic value is still controversial. The aim was to investigate the correlation between the SINS and ESCC and the association between SINS and ambulation before and survival after surgery. METHODS: Correlations were assessed between SINS and grades of ESCC in patients who underwent spine surgery for spinal metastases. CT and MRI were used to calculate SINS and the grades of ESCC respectively. Correlations were analyzed with the Spearman's correlation test. Postoperative survival was estimated with Kaplan-Meier analysis and survival curves were compared with the log-rank test. The Cox proportional hazard model was used to assess the effect of prognostic variables including age, ambulation before surgery, SINS, and the Karnofsky Performance Status (KPS) as covariates. RESULTS: The study included 256 patients (196 men and 60 women) with a median age of 70 (24-88) years. The mean SINS was 10. One hundred fifty-two patients (59%) had lost ambulation before surgery. One hundred and one patients had grades 0-2 and 155 patients had grade 3 according to the ESCC-scale. SINS correlated with the grades of ESCC (p = 0.001). The SINS score was not associated with ambulation before surgery (p = 0.63). The median postoperative survival was 10 months, and there was no difference in postoperative survival between the SINS categories (p = 0.25). The ability to walk before surgery and a high KPS were associated with longer postoperative survival. CONCLUSION: SINS correlated with grades of ESCC, which implies that higher SINS may be considered as an indicator of risk for developing ESCC. The SINS was not associated with ambulation before or survival after surgery.
Assuntos
Compressão da Medula Espinal , Neoplasias da Coluna Vertebral , Humanos , Masculino , Compressão da Medula Espinal/cirurgia , Compressão da Medula Espinal/etiologia , Feminino , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/mortalidade , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Adulto Jovem , Prognóstico , Instabilidade Articular/cirurgia , Instabilidade Articular/etiologiaRESUMO
PURPOSE: This study aimed to clarify the dosimetric impact of the respiratory motion of the liver on stereotactic body radiation therapy (SBRT) for spine metastasis and examine the utility of introducing beam avoidance (beam-off at specific gantry angles). METHODS: A total of 112 consecutive patients who underwent SBRT for spine metastasis between 2018 and 2024 were examined. Overall, 15 patients who had lesions near the liver dome were included in this study. Retrospective treatment plans were generated using computed tomography (CT) images acquired during inhalation and exhalation to evaluate the dosimetric impact of respiratory motion of the liver. The dose difference (DD) and relative value (DD%) were evaluated using the dose-volume histogram (DVH) metrics, planning target volume Dmax, D95%, spinal cord D0.035 cc, and esophagus D2.5 cc. The magnitude of the liver movements was evaluated based on differences of liver size Lave at the isocentric axial plane between the inspiratory and expiratory CT images. RESULTS: The DD in almost all DVH metrics tended to increase when the liver moved away from the target during inhalation: For example, Mean ± $ \pm $ a standard deviation (SD) DD in PTV D95% for the treatment plan incorporating beam avoidance and those without beam avoidance was 0.5 ± $\pm$ 0.3 and 0.9 ± $ \pm $ 0.6 Gy, respectively. The spinal cord D0.035 cc for those shows 0.4 ± $ \pm $ 0.2 and 0.7 ± $ \pm $ 0.7 Gy, respectively. The treatment plans without beam avoidance also showed moderate or strong correlations between Lave and DD for almost all DVH metrics. No correlation was seen in the beam avoidance plan. The spinal cord D0.035 cc revealed approximately 1 Gy or +4% in DD when Lave was < -4 cm. CONCLUSIONS: Respiratory motion of the liver dome can cause substantial dosimetric discrepancies in the dose delivered to the spinal cord, although the extent depends on patient variables. Dose assessment should be performed for determining the appropriate means of respiratory management, such as breath-hold. Alternatively, beam avoidance effectively mitigates the impact.
RESUMO
BACKGROUND: Spine stereotactic body radiation therapy (SBRT) for the treatment of metastatic disease is increasingly utilized owing to improved pain and local control over conventional regimens. Vertebral body collapse (VBC) is an important toxicity following spine SBRT. We investigated our institutional experience with spine SBRT as it relates to VBC and spinal instability neoplastic score (SINS). PATIENTS AND METHODS: Records of 83 patients with 100 spinal lesions treated with SBRT between 2007 and 2022 were reviewed. Clinical information was abstracted from the medical record. The primary endpoint was post-treatment VBC. Logistic univariate analysis was performed to identify clinical factors associated with VBC. RESULTS: Median dose and number of fractions used was 24 Gy and 3 fractions, respectively. There were 10 spine segments that developed VBC (10%) after spine SBRT. Median time to VBC was 2.4 months. Of the 11 spine segments that underwent kyphoplasty prior to SBRT, none developed subsequent VBC. No factors were associated with VBC on univariate analysis. CONCLUSIONS: The rate of vertebral body collapse following spine SBRT is low. Prophylactic kyphoplasty may provide protection against VBC and should be considered for patients at high risk for fracture.
RESUMO
Around 40% of cancer patients present with spinal metastases (SM), the lumbar spine being the second most involved site (15%-30%) after the thoracic (60%-80%). Since the development of separation surgery, minimally invasive surgery (MIS) has increasingly been applied to approach SM, mirroring benefits yielded in the degenerative realm. Moreover, preoperative embolization potentially enhances local control for certain radioresistant histologies. Carbon fiber-reinforced PEEK hardware reduces image artifact, facilitating more accurate follow-up and radiotherapeutic planning. Additionally, short-segment cement-augmented constructs may be beneficial to decrease surgical morbidity and operative risk in this population. The authors present a lumbar spinal metastasis treated with MIS techniques. The video can be found here: https://stream.cadmore.media/r10.3171/2024.1.FOCVID23222.
RESUMO
Introduction: Delayed surgical management of spinal metastases (SMs) can have detrimental effects on patient survival and quality of life, leading to pain and potential neurological impairment. This study aimed to assess the impact of delayed referral for SMs on clinical outcomes by analyzing patients managed in emergency situations. Methods: We retrospectively reviewed the data of all patients admitted on either emergency or elective basis who underwent surgery for the treatment of neoplastic spine lesions at our two institutions (tertiary referral neurosurgical units) between January 2008 and December 2019. Results: We analyzed 210 elective (EGp) and 323 emergency patients (UGp); emergencies increased significantly over the 12-year period, with a Friday peak (39.3%) and frequent neurological impairment (61.6% vs. 20%). Among the UGp patients, 186 (7.5%) had a previously monitored primitive cancer, including 102 (31.6%) with known SMs. On admission, 71 of the 102 (69.9%) patients presented with neurological deficits. UGp patients were more likely to undergo a single decompression without fixation. Outcomes at the 3-month follow-up were significantly worse for UGp patients ([very] poor, 29.2 vs. 13.8%), and the median overall survival for UGp patients was statistically lower. Risk factors for patients with SM undergoing emergency management included short delay between onset of symptoms and first contact with a spine surgeon, and an initial motor deficit. Conclusion: Many patients with previously identified metastases, including those with neurological deficits, are urgently referred. Optimization is needed in the oncology pathway, and all stakeholders must be made aware of the factors contributing to the improvement in the clinical and radiological identification of potential complications affecting patient survival and quality of life.
RESUMO
Background and Objectives: The mechanisms involved in the development of brain metastasis (BM) remain elusive. Here, we investigated whether BM is associated with spine involvement in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: A consecutive 902 patients with metastatic NSCLC were included from the Inha Lung Cancer Cohort. Patients with BM at diagnosis or subsequent BM development were evaluated for both spine involvement in NSCLC and anatomic proximity of BM to the cerebrospinal fluid (CSF) space. Results: At diagnosis, BM was found in 238 patients (26.4%) and bone metastasis was found in 393 patients (43.6%). In patients with bone metastasis, spine involvement was present in 280 patients. BM subsequently developed in 82 (28.9%) of 284 patients without BM at diagnosis. The presence of spine metastasis was associated with BM at diagnosis and subsequent BM development (adjusted odd ratios and 95% confidence intervals = 2.42 and 1.74-3.37, p < 0.001; 1.94 and 1.19-3.18, p = 0.008, respectively). Most patients with spine metastasis, either with BM at diagnosis or subsequent BM, showed BM lesions located adjacent (within 5mm) to the CSF space (93.8% of BM at the diagnosis, 100% of subsequent BM). Conclusions: These findings suggest that the presence of spine involvement is a risk factor for BM development in NSCLC patients with bone metastasis.
Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Razão de Chances , PacientesRESUMO
Bone turnover and microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This exploratory study aimed to establish an initial understanding of microdamage accumulation and load to failure in healthy and osteolytic rat vertebrae following focal and systemic cancer treatment (docetaxel (DTX), stereotactic body radiotherapy (SBRT), or zoledronic acid (ZA)). Osteolytic spine metastases were developed in 6-week-old athymic female rats via intracardiac injection of HeLa human cervical cancer cells (day 0). Additional rats served as healthy controls. Rats were either untreated, received SBRT to the T10-L6 vertebrae on day 14 (15 Gy, two fractions), DTX on day 7 or 14, or ZA on day 7. Rats were euthanized on day 21. Tumor burden was assessed with bioluminescence images acquired on day 14 and 21, histology of the excised T11 and L5 vertebrae, and ex-vivo µCT images of the T13-L4. Microstructural parameters (bone volume/total volume, trabecular number, spacing, thickness, and bone mineral density) were measured from L2 vertebrae. Load to failure was measured with axial compressive loading of the L1-L3 motion segments. Microdamage accumulation was labeled in T13 vertebrae with BaSO4 staining and was visualized with high resolution µCT imaging. Microdamage volume fraction was defined as the ratio of BaSO4 to bone volume. DTX administered on day 7 reduced tumor growth significantly (p < 0.05). Microdamage accumulation was found to be increased by the presence of metastases but was reduced by all treatments with ZA showing the largest improvement in HeLa cell injected rats. Load to failure was decreased in untreated and SBRT HeLa cell injected rats compared to healthy controls (p < 0.01). There was a moderate negative correlation between load to failure and microdamage volume fraction in vertebrae from rats injected with HeLa cells (R = -0.35, p = 0.031). Strong correlations were also found between microstructural parameters and load to failure and microdamage accumulation. Several factors, including the presence of osteolytic lesions and use of cancer therapies, influence microdamage accumulation and load to failure in rat vertebrae. Understanding the impact of these treatments on fracture risk of metastatic vertebrae is important to improve management of patients with spinal metastases.
Assuntos
Fraturas Ósseas , Vértebras Lombares , Ratos , Humanos , Feminino , Animais , Células HeLa , Vértebras Lombares/patologia , Densidade Óssea , Fraturas Ósseas/patologia , Vértebras TorácicasRESUMO
BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is an exceptionally rare soft tissue neoplasm. This tumor primarily presents as a benign soft tissue lesion in children with an average age of 14 years. The standard treatment regimen is wide local excision with interval follow-up. However, newer reports have demonstrated malignant potential with the possibility of intracranial metastasis. OBSERVATIONS: A 45-year-old male with no soft tissue primary tumor presented with a primary intracranial lesion and thoracic spine metastasis refractory to chemotherapy and radiation treatment. LESSONS: This report illustrates the potential for a highly malignant nature of metastatic AFH. In addition, the authors demonstrate an incidence of AFH in a middle-aged male without a primary soft tissue or skin lesion. This report highlights the importance of prompt treatment and excision for AFH, as there is still little understanding of successful options for systemic therapy.
RESUMO
BACKGROUND: Metastatic epidural spinal cord compression (MESCC) and pathological vertebral compression fractures (pVCF) are the most serious debilitating morbidities of spine metastases (SpMs) causing devastating neurological damages. The respective impact of these two metastasis-spreading entities on survival and on neurological damage is debated. METHODS: A French prospective cohort study collected 279 consecutive patients presenting with SpMs between January 2017 and 2021. We compared 174 patients with MESCC and 105 patients with pVCF. RESULTS: The median Overall Survival (OS) for the MESCC group was 13.4 months (SD 1.5) vs 19.2 months (SD 2.3) for pVCF patients (p = 0.085). Sixty-five patients (23.3 %) were operated on: 49/65 (75.4 %) in the MESCC group and 16/65 (15.2 %) in the pVCF group, p < 0.0001. At 6 months FU, in the MESCC group, 21/44 (45.4 %) of non-ambulatory patients at onset improved to ambulatory status (Frankel D-E) vs 10/13 (76.9 %) in the pVCF group (p = 0.007). In multivariable analysis with the Cox proportional hazard model, good ECOG-PS and SINS Score 7-12 [HR: 6.755, 95 % CI 2.40-19.00; p = 0.001] were good prognostic factors for preserved ambulatory neurological status. However, SpMs diagnosed synchronously with the primary tumor [HR: 0.397, 95 % CI 0.185-0.853; p = 0.018] and MESCC [HR: 0.058, 95 % CI 0.107-0.456; p = 0.007] were independent risk factors for impaired neurological function. CONCLUSION: Contrary to pVCF, MESCC causes neurological damage. Nevertheless, neurological recovery remains possible. MESCC and pVCF have no impact on survival. The management of MESCC remains to be clarified and optimized to reduce neurological damage.
Assuntos
Fraturas por Compressão , Fraturas Espontâneas , Compressão da Medula Espinal , Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral , Humanos , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Fraturas por Compressão/complicações , Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/secundário , Descompressão Cirúrgica/efeitos adversos , Prognóstico , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/cirurgiaRESUMO
OBJECTIVE: Spine metastases are commonly treated with radiotherapy for local tumor control; pathologic fracture is a potential complication of spinal radiotherapy. Both Hounsfield units (HUs) on CT and vertebral bone quality (VBQ) on MRI have been argued to predict stability as measured by odds of pathologic fracture, although it is unclear if there is a difference in the predictive power between the two methodologies. The objective of the present study was to examine whether one methodology is a better predictor of pathologic fracture following radiotherapy for mobile spine metastases. METHODS: Patients who underwent radiotherapy (conventional external-beam radiation therapy, stereotactic body radiation therapy, or intensity-modulated radiation therapy) for mobile spine (C1-L5) metastases at a tertiary care center were retrospectively identified. Details regarding underlying pathology, patient demographics, and tumor morphology were collected. Vertebral involvement was assessed using the Weinstein-Boriani-Biagini (WBB) system. Bone quality of the non-tumor-involved bone was assessed on both pretreatment CT and MRI. Univariable analyses were conducted to identify independent predictors of fracture, and Kaplan-Meier analyses were used to identify significant predictors of time to pathologic fracture. Stepwise Cox regression analysis was used to determine independent predictors of time to fracture. RESULTS: One hundred patients were included (mean age 62.7 ± 11.9 years; 61% male), of whom 35 experienced postradiotherapy pathologic fractures. The most common histologies were lung (22%), prostate (21%), breast (14%), and renal cell (13%). On univariable analysis, the mean HUs of the vertebrae adjacent to the fractured vertebra were significantly lower among those experiencing fracture; VBQ was not significantly associated with fracture odds. Survival analysis showed that average HUs ≤ 132, nonprostate pathology, involvement of ≥ 3 vertebral body segments on the WBB system, Spine Instability Neoplastic Score (SINS) ≥ 7, and the presence of axial pain all predicted increased odds of fracture (all p < 0.001). Cox regression found that HUs ≤ 132 (OR 2.533, 95% CI 1.257-5.103; p = 0.009), ≥ 3 WBB vertebral body segments involved (OR 2.376, 95% CI 1.132-4.987; p = 0.022), and axial pain (OR 2.036, 95% CI 0.916-4.526; p = 0.081) predicted increased fracture odds, while prostate pathology predicted decreased odds (OR 0.076, 95% CI 0.009-0.613; p = 0.016). Sensitivity analysis suggested that an HU threshold of ≤ 132 and a SINS of ≥ 7 identified patients at increased risk of fracture. CONCLUSIONS: The present results suggest that bone density surrogates as measured on CT, but not MRI, can be used to predict the risk of pathologic fracture following radiotherapy for mobile spine metastases. More extensive vertebral body involvement and the presence of mechanical axial pain additionally predict increased fracture odds.
Assuntos
Fraturas Espontâneas , Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/complicações , Fatores de Risco , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , DorRESUMO
Three-dimensional (3D) printing technology has proven to have many advantages in spine and sacrum surgery. 3D printing allows the manufacturing of life-size patient-specific anatomic and pathologic models to improve preoperative understanding of patient anatomy and pathology. Additionally, virtual surgical planning using medical computer-aided design software has enabled surgeons to create patient-specific surgical plans and simulate procedures in a virtual environment. This has resulted in reduced operative times, decreased complications, and improved patient outcomes. Combined with new surgical techniques, 3D-printed custom medical devices and instruments using titanium and biocompatible resins and polyamides have allowed innovative reconstructions.
Assuntos
Neoplasias , Impressão Tridimensional , Humanos , Desenho Assistido por Computador , Sacro/diagnóstico por imagem , Sacro/cirurgiaRESUMO
PURPOSE: To develop and evaluate a quantile regression-based blood loss prediction model for open surgery of spinal metastases. METHODS: This was a multicenter retrospective cohort study. Over a 11-year period, patients underwent open surgery for spinal metastases at 6 different institutions were reviewed. The outcome measure is intraoperative blood loss (in mL). The effects of baseline, histology of primary tumor and surgical procedure on blood loss were evaluated by univariate and multivariate analysis to determine the predictors. Multivariate ordinary least squares (OLS) regression and 0.75 quantile regression were used to establish two prediction models. The performance of the two models was evaluated in the training set and the test set, respectively. RESULTS: 528 patients were included in this study. Mean age was 57.6 ± 11.2 years, with a range of 20-86 years. Mean blood loss was 1280.1 ± 1181.6 mL, with a range of 10 ~ 10,000 mL. Body mass index (BMI), tumor vascularization, surgical site, surgical extent, total en bloc spondylectomy and microwave ablation use were significant predictors of intraoperative blood loss. Hypervascular tumor, higher BMI, and broader surgical extent were related with massive blood loss. Microwave ablation is more beneficial in surgery with substantial blood loss. Compared to the OLS regression model, the 0.75 quantile regression model may decrease blood loss underestimate. CONCLUSION: In this study, we developed and evaluated a prediction model for blood loss in open surgery for spinal metastases based on 0.75 quantile regression, which may minimize blood loss underestimate.
Assuntos
Perda Sanguínea Cirúrgica , Neoplasias da Coluna Vertebral , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Coluna Vertebral/secundário , Estudos RetrospectivosRESUMO
OBJECTIVE: Group patients who required open surgery for metastatic breast cancer to the spine by functional level and metastatic disease characteristics to identify factors that predispose to poor outcomes. METHODS: A retrospective analysis included patients managed at 2 tertiary referral centers from 2008 to 2020. The primary outcome was a 90-day adverse event. A 2-step unsupervised cluster analysis stratified patients into cohorts using function at presentation, preoperative spine radiation, structural instability, epidural spinal cord compression (ESCC), neural deficits, and tumor location/hormone status. Comparisons were performed using χ2 test and one-way analysis of variance. RESULTS: Five patient "clusters" were identified. High function (HIGH) had thoracic metastases and an Eastern Cooperative Oncology Group (ECOG) score of 1.0 ± 0.8. Low function/irradiated (LOW + RADS) had preoperative radiation and the lowest Karnofsky scores (56.0 ± 10.6). Estrogen receptor or progesterone receptor (ER/PR) positive patients had >90% estrogen/progesterone positivity and moderate Karnofsky scores (74.0 ± 11.5). Lumbar/noncompressive (NON-COMP) had the fewest patients with ESCC grade 2 or 3 epidural disease (42.1%, P < 0.001). Low function/neurologic deficits (LOW + NEURO) had ESCC grade 2 or 3 disease and neurologic deficits. Adverse event rates were 25.0% in the HIGH group, 73.3% in LOW + RADS, 24.0% in ER/PR, 31.6% in NON-COMP, and 60.0% in LOW + NEURO (P = 0.003). CONCLUSIONS: Function at presentation, tumor hormone signature, radiation history, and epidural compression delineated postoperative trajectory. We believe our results can aid in expectation management and the identification of at-risk patients who may merit closer surveillance following surgical intervention.
Assuntos
Neoplasias da Mama , Leucemia Mieloide Aguda , Compressão da Medula Espinal , Neoplasias da Coluna Vertebral , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Estudos Retrospectivos , Inteligência Artificial , Neoplasias da Coluna Vertebral/secundário , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Compressão da Medula Espinal/patologia , Análise por ConglomeradosRESUMO
Metastatic lesions of the spine occur in up to 40% of cancer patients and are a frequent source of pain and neurologic deficit due to cord compression. Palliative radiotherapy is the main first-intent local treatment in the form of single-fraction radiotherapy or fractionated courses. Reirradiation is a viable option for inoperable patients where spinal decompression is needed but with an increased risk of radiation-induced myelopathy (RM) and subsequent neurologic damage. This review summarizes reported data on local treatment options after initial irradiation in patients with relapsed spine metastasis and key dosimetric correlations between the risk of spinal cord injury and reirradiation technique, total dose, and time between treatments. The Linear Quadratic (LQ) model was used to convert all the published doses into biologically effective doses and normalize them to EQD2. For 3D radiotherapy, authors used cumulative doses from 55.2 Gy2/2 to 65.5 Gy2/2 EQD2 with no cases of RM mentioned. We found little evidence of RM after SBRT in the papers that met our criteria of inclusion, usually at the median reported dose to critical neural tissue around 93.5 Gy2/2. There is a lack of consistency in reporting the spinal cord dose, which leads to difficulty in pooling data.
RESUMO
OBJECTIVE: The vertebral column is the most common site for skeletal metastasis, often leading to debilitating pain and weakness. Metastatic cancer has unique genetic drivers that potentiate tumorigenicity. There is an unmet need for novel targeted therapy in patients with spinal metastatic disease. METHODS: The authors assessed the effect of verteporfin-induced yes-associated protein (YAP) inhibition on spine metastatic cell tumorigenicity and radiation sensitivity in vitro. Animal studies used a subcutaneous xenograft mouse model to assess the use of systemic intraperitoneal verteporfin (IP-VP) and intratumoral verteporfin microparticles (IT-VP) to inhibit the tumorigenicity of lung and breast spinal metastatic tumors from primary patient-derived tissue. RESULTS: Verteporfin led to a dose-dependent decrease in migration, clonogenicity, and cell viability via inhibition of YAP and downstream effectors cyclin D1, CTGF, TOP2A, ANDRD1, MCL-1, FOSL2, KIF14, and KIF23. This was confirmed with knockdown of YAP. Verteporfin has an additive response when combined with radiation, and knockdown of YAP rendered cells more sensitive to radiation. The addition of verteporfin to YAP knockdown cells did not significantly alter migration, clonogenicity, or cell viability. IP-VP and IT-VP led to diminished tumor growth (p < 0.0001), especially when combined with radiation (p < 0.0001). Tissue analysis revealed diminished expression of YAP (p < 0.0001), MCL-1 (p < 0.0001), and Ki-67 (p < 0.0001) in tissue from verteporfin-treated tumors compared with vehicle-treated tumors. CONCLUSIONS: This is the first study to demonstrate that verteporfin-mediated inhibition of YAP leads to diminished tumorigenicity in lung and breast spinal metastatic cancer cells. Targeting of YAP with verteporfin offers promising results that could be translated to human clinical trials.
Assuntos
Neoplasias da Mama , Fatores de Transcrição , Humanos , Animais , Camundongos , Feminino , Verteporfina/farmacologia , Verteporfina/uso terapêutico , Proteína de Sequência 1 de Leucemia de Células Mieloides , Fatores de Transcrição/metabolismo , Fatores de Transcrição/farmacologia , Linhagem Celular Tumoral , Neoplasias da Mama/tratamento farmacológico , Pulmão/metabolismo , Proliferação de CélulasRESUMO
PURPOSE: Given the rarity of disseminated disease at the time of initial evaluation for pediatric brain tumor patients, we sought to identify clinical and radiographic predictors of spinal metastasis (SM) at the time of presentation. METHODS: We performed a single-institution retrospective chart review of pediatric brain tumor patients who first presented between 2004 and 2018. We extracted information regarding patient demographics, radiographic attributes, and presenting symptoms. Univariate and multivariate logistic regression was used to estimate the association between measured variables and SMs. RESULTS: We identified 281 patients who met our inclusion criteria, of whom 19 had SM at initial presentation (6.8%). The most common symptoms at presentation were headache (n = 12; 63.2%), nausea/vomiting (n = 16; 84.2%), and gait abnormalities (n = 8; 41.2%). Multivariate models demonstrated that intraventricular and posterior fossa tumors were more frequently associated with SM (OR: 5.28, 95% CI: 1.79-15.59, p = 0.003), with 4th ventricular (OR: 7.42, 95% CI: 1.77-31.11, p = 0.006) and cerebellar parenchymal tumor location (OR: 4.79, 95% CI: 1.17-19.63, p = 0.030) carrying the highest risk for disseminated disease. In addition, evidence of intracranial leptomeningeal enhancement on magnetic resonance imaging (OR: 46.85, 95% CI: 12.31-178.28, p < 0.001) and hydrocephalus (OR: 3.19; 95% CI: 1.06-9.58; p = 0.038) were associated with SM. CONCLUSIONS: Intraventricular tumors and the presence of intracranial leptomeningeal disease were most frequently associated with disseminated disease at presentation. These findings are consistent with current clinical expectations and offer empirical evidence that heightened suspicion for SM may be prospectively applied to certain subsets of pediatric brain tumor patients at the time of presentation.
Assuntos
Neoplasias Encefálicas , Hidrocefalia , Criança , Humanos , Estudos Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Cefaleia , Imageamento por Ressonância MagnéticaRESUMO
STUDY DESIGN: International survey. OBJECTIVES: To assess variability in the treatment practices for spinal metastases as a function of practice setting, surgical specialty, and fellowship training among an international group of spine surgeons. METHODS: An anonymous internet-based survey was disseminated to the AO Spine membership. The questionnaire contained items on practice settings, fellowship training, indications used for spinal metastasis surgery, surgical strategies, multidisciplinary team use, and postoperative follow-up priorities and practice. RESULTS: 341 gave complete responses to the survey with 76.3% identifying spinal oncology as a practice focus and 95.6% treating spinal metastases. 80% use the Spinal Instability Neoplastic Score (SINS) to guide instrumentation decision-making and 60.7% recruit multidisciplinary teams for some or all cases. Priorities for postoperative follow-up are adjuvant radiotherapy (80.9%) and systemic therapy (74.8%). Most schedule first follow-up within 6 weeks of surgery (62.2%). Significant response heterogeneity was seen when stratifying by practice in an academic or university-affiliated center, practice in a cancer center, completion of a spine oncology fellowship, and self-identification as a tumor specialist. Respondents belonging to any of these categories were more likely to utilize SINS (P < .01-.02), recruit assistance from plastic surgeons (all P < .01), and incorporate radiation oncologists in postoperative care (P < .01-.03). CONCLUSIONS: The largest variability in practice strategies is based upon practice setting, spine tumor specialization, and completion of a spine oncology fellowship. These respondents were more likely to use evidenced-based practices. However, the response variability indicates the need for consensus building, particularly for postoperative spine metastasis care pathways and multidisciplinary team use.
RESUMO
STUDY DESIGN: Retrospective case-control study. OBJECTIVES: The aim of this study was to develop a simple and reliable imaging parameter to predict postoperative ambulatory status in patients with metastatic epidural spinal cord compression (MESCC). METHODS: Sixty-three patients with MESCC underwent spine surgery because of neurologic deficits were included. On preoperative axial MRI, the cord compression ratio was analyzed for postoperative ambulatory status. The relationship between other imaging features, such as fracture of the affected vertebra and increased T2 signal intensity of the spinal cord at the compression level, and the postoperative ambulatory status were also analyzed. RESULTS: Cord compression ratio and increased T2 signal change of the spinal cord were significantly different between the postoperative ambulatory group and the non-ambulatory group. Receiver operating characteristic analysis showed that the optimal cut-off value was 0.84. In the multivariate regression analysis, only a cord compression ratio of more than 0.84 was significantly associated with postoperative ambulatory status (odds ratio = 10.80; 95% confidence interval = 2.79-41.86; P = .001). Interobserver/intraobserver agreements were strong for the cord compression ratio, however those agreements were weak for increased T2 signal intensity. CONCLUSIONS: On preoperative MRI, the cord compression ratio may predict postoperative ambulatory status in patients with MESCC. The measurement of this imaging parameter was simple and reliable. This imaging predictor may be helpful for both clinicians and patients.
RESUMO
Purpose: To understand the current practice of radiation oncologists (ROs) and orthopedic surgeons (OSs) regarding spine metastasis. Methods: In 2022, an internet-based survey was conducted for ROs and OSs who treat spinal metastasis in Korea. Respondents were asked to choose the treatment option for two clinical scenarios. Scenario 1 involved a case displaying symptoms of leg weakness due to spinal cord compression and Scenario 2 involved a case with back pain due to pathologic compression fracture. The survey also included a question that required respondents to rank the importance of 11 clinical factors that affect treatment decisions. Results: Forty-nine ROs and 30 OSs responded to the survey. There were significant differences in treatment choices between two groups for both scenarios (P = 0.001). In Scenario 1, more OSs chose surgical resection than ROs (43.3% vs. 16.7%), while more ROs chose radiotherapy than OSs (83.3% vs. 53.3%). In Scenario 2, a similar proportion of OSs and ROs chose radiotherapy (OSs, 71.4% vs. ROs, 67.3%), while more OSs opted for prophylactic fixation after radiotherapy than ROs (95.0% vs. 42.4%). The top three factors influencing treatment decisions were general performance status, life expectancy, and spinal instability for both ROs and OSs. In both Scenarios 1 and 2, the treatment decisions of ROs changed significantly when clinical conditions related to these top three factors were altered. Conclusion: Although ROs and OSs share the same factors influencing treatment decisions for spinal metastases, notable differences exist in their actual treatment preferences, with ROs preferring radiotherapy and OSs opting for surgical resection. Multidisciplinary discussions may be necessary to reduce the gap in decision-making.