Clinical characteristics and prognosis of high-risk neuroblastoma patients with skeletal metastases at different sites / 中华实用儿科临床杂志

Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.

Determination of early bone metastasis on Bone Scans Using the Gray Levels Histogram / Búsqueda de metástasis ósea temprana en gammagramas óseos usando el histograma de tonos de gris

ABSTRACT The aim of this paper is to show a technique to speed up the interpretation of bone scans in order to determine the presence of early bone metastasis. This is done using the gray levels histogram of the region of interest. The technique is intended to assist in the bone scans interpretation in order to provide a successful diagnosis. During the analysis, three types of histograms were observed on the regions of interest. If the histogram is narrow and shifted toward the origin, the bone scan is free of metastasis. If it is shifted to the right and slightly broadened, indicates the presence of a bone anomaly different from a metastasis. On the other hand, if the histogram is more broadened and shifted to the right, is suggests the presence of metastasis. This histogram is characterized by displaying small curls on the right side providing information about the metastatic disease stage, which could be low-amplitude peaks and have a short length, if the metastasis is in early stage, or high-amplitude peaks and a long length, if is advanced. Finally, the analyzed region is displayed in false color considering the minimum gray levels observed in the histogram.

Visualizando Gammagramas Óseos en Colores / Displaying Bone Scans in Color

Resumen En este trabajo se describe el uso de un software para detectar metástasis óseas en gammagramas cuyo funcionamiento está basado en un método cuantitativo. En la investigación se incluyeron cuarenta y tres gammagramas óseos de pacientes con cáncer de próstata, los cuales fueron previamente analizados visualmente por tres especialistas y su diagnóstico se tomó como referencia. Debido a que no todos los huesos de un paciente muestran los mismos tonos de gris, cada uno de los gammagramas se segmentó para su análisis en cuatro regiones: cráneo, hombros, tórax y pelvis. La segmentación se hizo con el fin de obtener intervalos de tonos de gris en cada una de las regiones empleando un proceso estadístico. Para ello se calcularon la media y la desviación estándar de cuatro muestras que contenían cada una cuarenta y tres regiones. Tomando en consideración los intervalos, siete colores fueron asignados a cada región. Mediante los colores fue posible diferenciar los casos sanos e infiltrados en cada región, lo que facilita el diagnóstico. Se muestran ejemplos de los resultados en cada una de las regiones.

Abstract The use of software based on a quantitative method for detecting skeletal metastasis in bone scans is presented. Forty-three bone scans of patients with prostate cancer were previously analyzed visually by three specialists and their diagnosis were taken as a reference. Later, these scans were analyzed by segmenting them into four regions: skull, shoulders, chest, and pelvis. The segmentation was made to obtain intervals of gray levels for each of the regions using a statistical process. Tríese values were found by calculating the mean and standard deviation of four samples containing each forty-three regions. Using these intervals, seven colors were assigned to each region. By means of the colors it is possible to differentiate healthy and infiltrated cases in each region, which may facilitate the diagnosis. Examples of results in each region are shown.

Outcome of Skeletal Reconstructive Surgery for Metastatic Bone Tumours in the Femur

Introduction: The role of surgery in skeletal metastasis is to reduce morbidity and improve the quality of life in terminally ill patients. We report our experience with patients who underwent skeletal reconstructive surgery for metastatic bone tumour of the femur. Materials and Methods: Twenty nine operations for skeletal metastasis of the femur performed in our centre between 2009 and 2015 were included in this study. We evaluated the choice of implant, complications, survival rate and functional outcome. Fourteen patients were still alive at the time of this report for assessment of functional outcome using Musculoskeletal Tumour Society (MSTS) form. Results: Plating osteosynthesis with augmented-bone cement was the most common surgical procedure (17 patients) performed followed by arthroplasty (10 patients) and intramedullary nailing (2 patients) There were a total of five complications which were implant failures (2 patients), surgical site infection (2 patients), and site infection mortality (1 patient). The median survival rate was eight months. For the functional outcome, the mean MSTS score was 66%. Conclusion: Patients with skeletal metastasis may have prolonged survival and should undergo skeletal reconstruction to reduce morbidity and improve quality of life. The surgical construct should be stable and outlast the patient to avoid further surgery.

Serum alkaline phosphatase predicts survival outcomes in patients with skeletal metastatic nasopharyngeal carcinoma

OBJECTIVE: Bone metastasis is frequently associated with nasopharyngeal carcinoma. The diagnosis and follow-up of bone metastatic patients usually relies on skeletal X-ray and bone scintigraphy, which are time-consuming and costly. This study aimed to evaluate whether serum alkaline phosphatase offers clinical value in predicting the clinical response and survival outcome for skeletal metastatic nasopharyngeal carcinoma. METHODS: Serum alkaline phosphatase was measured at baseline and then before each cycle of treatment in 416 nasopharyngeal carcinoma patients with bone metastasis. The correlations between the pre-treatment and post-treatment alkaline phosphatase levels and the treatment efficacy were analyzed using the chi-square test. Survival was analyzed using the Kaplan–Meier method and then compared using the log-rank test. RESULTS: Patients with elevated pre-treatment alkaline phosphatase (>110 IU/L) had significantly worse progression-free survival (P<0.001) and overall survival (P<0.001) than those with a normal level of this marker (≤110 IU/L). Patients with elevated post-treatment alkaline phosphatase had worse progression-free survival (P<0.001) and overall survival (P<0.001) compared with those with a normal level. Patients with normal pre-treatment and post-treatment alkaline phosphatase showed the most favorable prognosis. The Cox multivariate analysis revealed that only the pre-treatment and post-treatment alkaline phosphatase levels were independent prognostic factors for progression-free survival (HR ϝ 1.656, P<0.001; HR ϝ 2.226, P<0.001) and for overall survival (HR ϝ 1.794, P<0.001; HR ϝ 2.657, P<0.001). CONCLUSIONS: Serum alkaline phosphatase appears to be a significant independent prognostic index in patients with skeletal metastatic nasopharyngeal carcinoma, which could reflect the short-term treatment response ...

Estudio biocinético y dosimétrico de un kit de producción local de 177Lu-EDTMP para su uso como agente paliativo del dolor / Biokinetic and dosimetric study of 177Lu-EDTMP in the palliative treatment of skeletal metastasis

Los radiofármacos con afinidad por el tejido óseo como el ácido etilen-diamino-tetrametilen-fosfónico (EDTMP) marcado con radioisótopos emisores beta- han demostrado su eficacia en el tratamiento paliativo de las metástasis óseas. Se realizó un estudio biocinético y dosimétrico del 177Lu-EDTMP en ratones NIH. Los resultados obtenidos fueron extrapolados a humanos. Se estimó la dosis absorbida en órganos para dos modelos: un hombre adulto y una mujer adulta. El 177Lu-EDTMP posee una selectiva captación en hueso, una rápida eliminación en sangre e insignificante captación en tejidos no óseos. La dosis en hueso estimada para el hombre se encuentra entre 14,7-15,3 cGy/mCi y entre 19,6-20,4 cGy/mCi para la mujer. La toxicidad en médula ósea representa el factor limitante de este tipo de terapia, y para evitar superar la dosis máxima que ésta puede tolerar (200 cGy), se encontró que la actividad máxima segura de 177Lu-EDTMP que puede ser inyectada al hombre (73,9Kg), corresponde a un valor de 1,01 mCi/kg y a un valor de 1,25 mCi/Kg para la mujer (56,9Kg).

Bone-seeking radiopharmaceuticals like the ethylenediaminetetramethylene phosphonic acid (EDTMP) labeled with beta--emitting radioisotopes have demonstrated their efficacy in the palliative treatment of skeletal metastasis. A biokinetic and dosimetric study of 177Lu-EDTMP in NIH mice was performed. The results obtained were extrapolated to human. We estimate the absorbed doses in organs for two models: an adult male and an adult female. 177Lu-EDTMP has a selective uptake in bone, a rapid elimination from blood and negligible uptake in non-skeletal tissues. The estimated dose in bone is between 14.7-15.3 cGy/mCi for men and between 19.6-20.4 cGy/mCi for women. Bone marrow toxicity represents the limiting factor in this kind of therapy, and to avoid exceed the maximum dose it can tolerate (200 cGy), it was found that the maximum safe activity of 177Lu-EDTMP to be injected to male (73.9 kg), corresponds to a value of 1.01 mCi/kg and a value of 1.25 mCi/kg for female (56.9 kg).