The risk of neurological deterioration while using neoadjuvant denosumab on patients with giant cell tumor of the spine presenting with epidural disease: a meta-analysis of the literature.

BACKGROUND CONTEXT: Giant cell tumor (GCT) of bone is most commonly a benign but locally aggressive primary bone tumor. Spinal GCTs account for 2.7% to 6.5% of all GCTs in bone. En bloc resection, which is the preferred treatment for GCT of the spine, may not always be feasible due to the location, extent of the tumor, and/or the patient's comorbidities. Neoadjuvant denosumab has recently been shown to be effective in downstaging GCT, decreasing the size and extent of GCTs. However, the risk of neurologic deterioration is of major concern for patients with epidural spinal cord compression due to spinal GCT. We experienced this concern when a patient presented to our institution with a midthoracic spinal GCT with progressive epidural disease. The patient was not a good surgical candidate due to severe cardiac disease and uncontrolled diabetes. In considering nonoperative management for this patient, we asked ourselves the following question: What is the risk that this patient will develop neurologic deterioration if we do not urgently operate and opt to treat him with denosumab instead? PURPOSE: The purpose of this study was to assess the literature to (1) determine the risk of neurological deterioration in patients receiving neoadjuvant denosumab for the treatment of spinal GCT and (2) to evaluate the secondary outcomes including radiographic features, surgical/technical complexity, and histological features after treatment. STUDY DESIGN/SETTING: Meta-analysis of the literature. PATIENT SAMPLE: Surgical cases of spinal GCT that (1) presented with type III Campanacci lesions, (2) had epidural disease classified as Bilsky type 1B or above and (3) received neoadjuvant denosumab therapy. OUTCOME MEASURES: The primary outcome measure of interest was neurologic status during denosumab treatment. Secondary outcome measures of interest included radiographic features, surgical/technical complexity, histological features, tumor recurrence, and metastasis. METHODS: Using predetermined inclusion and exclusion criteria, PubMed and Embase electronic databases were searched in August 2022 for articles reporting spinal GCTs treated with neoadjuvant denosumab and surgery. Keywords used were "Spine" AND "Giant Cell Tumor" AND "Denosumab." RESULTS: A total of 428 articles were identified and screened. A total of 22 patients from 12 studies were included for review. 17 patients were female (17/22, 77%), mean age was 32 years (18-62 years) and average follow-up was 21 months. Most GCTs occurred in the thoracic and thoracolumbar spine (11 patients, 50%), followed by 36% in the lumbar spine and 14% in the cervical spine. Almost half of the patients had neurological deficits at presentation (10/22 patients, 45%), and more than 60% had Bilsky 2 or 3 epidural spinal cord compression. None of the patients deteriorated neurologically, irrespective of their neurological status at presentation (p-value=.02, CI -2.58 to -0.18). There were no local recurrences reported. One patient was found to have lung nodules postoperatively. More than 90% of cases had decreased overall tumor size and increased bone formation. Surgical dissection was facilitated in more than 85% of those who had documented surgical procedures. Four patients (18%) underwent initial spinal stabilization followed by neoadjuvant denosumab and then surgical excision of the GCT. Regarding the histologic analyses, denosumab eradicated the giant cells in 95% of cases. However, residual Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL)-positive stromal cells were noted, in 27% (6 cases). CONCLUSIONS: Neoadjuvant denosumab was a safe and effective means of treating spinal GCTs prior to surgery. Neurologic status remained stable or improved in all cases included in our review, irrespective of the presenting neurologic status. The most appropriate dosage and duration of denosumab therapy is yet to be determined. We recommend future well-designed studies to further evaluate the use of neoadjuvant denosumab for patients with spinal GCT.

Single-Component Dual-Functional Autoboost Strategy by Dual Photodynamic and Cyclooxygenase-2 Inhibition for Lung Cancer and Spinal Metastasis.

Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single-component dual-functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)-generated HOCl. A representative prodrug (DHU-CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU-CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU-CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase-2 (COX-2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX-2. Downstream prostaglandins E2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU-CBA2 promotes infiltration and function of CD8+ T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single-component dual-functional prodrug activated by TME-specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX-2 inhibitor.

Valoración e indicaciones quirúrgicas: cirugía separación / Preoperative assessment and surgical indications: Separation surgery

La compresión neurológica se presenta entre el 10-20% de los pacientes que desarrollan una metástasis vertebral. En la última década, la evolución de las técnicas diagnósticas y médicas oncológicas, el cambio de la radiación convencional externa a la radiocirugía y los nuevos instrumentales quirúrgicos, han hecho que el tratamiento de estos pacientes deba de ser indicado de forma personalizada y en consenso, de forma multidisciplinar, en comisiones específicas.Hoy, el estado biológico del paciente, la presencia de inestabilidad mecánica, la valoración neurológica y el grado de compresión epidural, así como la mejor categorización pronóstica del tumor, se establecen como los factores de decisión previa a la indicación del tratamiento quirúrgico, tratamiento que ha pasado de un concepto «citorreductor» al de «separador» o «preparador» de la médula para asegurar una radiocirugía segura.(AU)

Neurological compression occurs in 10%-20% of patients who develop spinal metastases. In the last decade, the evolution of oncological diagnostic and medical techniques, the change from conventional external radiation to radiosurgery and the new surgical instruments have meant that the treatment of these patients must be indicated in a personalized manner and by consensus, multidisciplinary way, in specific commissions.Today, the biological state of the patient, the presence of mechanical instability, the neurological assessment and degree of epidural compression, as well as the best prognostic categorization of the tumor, are established as decision factors prior to the indication of surgical treatment, treatment that has passed from a cytoreductive concept to that of a spinal cord release from tumor in order to ensure safe radiosurgery.(AU)

[Translated article] Preoperative assessment and surgical indications: Separation surgery / Valoración e indicaciones quirúrgicas: cirugía de separación

La compresión neurológica se presenta entre el 10-20% de los pacientes que desarrollan una metástasis vertebral. En la última década, la evolución de las técnicas diagnósticas y médicas oncológicas, el cambio de la radiación convencional externa a la radiocirugía y los nuevos instrumentales quirúrgicos, han hecho que el tratamiento de estos pacientes deba de ser indicado de forma personalizada y en consenso, de forma multidisciplinar, en comisiones específicas.Hoy, el estado biológico del paciente, la presencia de inestabilidad mecánica, la valoración neurológica y el grado de compresión epidural, así como la mejor categorización pronóstica del tumor, se establecen como los factores de decisión previa a la indicación del tratamiento quirúrgico, tratamiento que ha pasado de un concepto «citorreductor» al de «separador» o «preparador» de la médula para asegurar una radiocirugía segura.(AU)

Neurological compression occurs in 10%-20% of patients who develop spinal metastases. In the last decade, the evolution of oncological diagnostic and medical techniques, the change from conventional external radiation to radiosurgery and the new surgical instruments have meant that the treatment of these patients must be indicated in a personalized manner and by consensus, multidisciplinary way, in specific commissions.Today, the biological state of the patient, the presence of mechanical instability, the neurological assessment and degree of epidural compression, as well as the best prognostic categorization of the tumor, are established as decision factors prior to the indication of surgical treatment, treatment that has passed from a cytoreductive concept to that of a spinal cord release from tumor in order to ensure safe radiosurgery.(AU)

Ablación tumoral y cementación en el tratamiento de las metástasis vertebrales. Estudio multicéntrico / Tumor ablation and vertebral augmentation in the treatment of vertebral metastases: A multicenter study

Introducción: El tratamiento de las fracturas vertebrales metastásicas sin compresión neural se realiza con técnicas percutáneas de cementación. El aumento de presión intratumoral por estas técnicas puede enviar células tumorales al torrente sanguíneo. Para evitar esa diseminación y mejorar el tratamiento del dolor se han introducido las técnicas de ablación que permitirían crear una cavidad en el tumor previo a la cementación o directamente necrosar la metástasis cuando el tamaño es pequeño. Material: Presentamos la experiencia con la ablación de dos hospitales y dos técnicas de ablación distintas. El primer grupo usó la ablación por radiofrecuencia (ARF) en 14 pacientes (26 vértebras) de los cuales en cuatro se asoció una artrodesis vertebral. El segundo grupo usó la ablación por microondas (AMO); 93 pacientes (129 lesiones) sin asociar instrumentación vertebral. Resultados: En el grupo de ARF la mejoría del dolor en la escala visual analógica (EVA) fue de 7,7 a 2,6 a las seis semanas. No hubo complicaciones derivadas de la ablación. En la mayoría de los casos se asoció la cementación. En el grupo de AMO la mejoría del dolor en EVA pasó de 6,8 a 1,7 a las seis semanas. En todos los casos se asoció la cementación. No hubo complicaciones derivadas de la ablación. Conclusiones: La asociación de las técnicas de ablación a la cementación vertebral es una técnica segura, que permite mejorar notablemente el dolor del paciente y puede ayudar al control de la enfermedad.(AU)

Introduction: Treatment of metastatic vertebral fractures without neural compression is performed with percutaneous cementation techniques. The increase in intratumoral pressure by these techniques can send tumor cells into the bloodstream. To prevent this dissemination and improve pain treatment, ablation techniques have been introduced that would allow the creation of a cavity in the tumor prior to cementation or directly necrosing the metastasis when its size is small. Material: We present the experience with ablation of two hospitals and two different ablation techniques. The first group used radiofrequency ablation (A) in 14 patients (26 vertebrae), 4 of whom underwent vertebral arthrodesis. The second group used microwave ablation (B) in 93 patients (129 lesions) without associated vertebral instrumentation. Results: In group A pain improvement in VAS was 7.7–2.6 at 6 weeks. There were no complications derived from the ablation. In most cases cementation was associated. In the group B pain improvement in VAS went from 6.8–1.7 at 6 weeks. Cementation was associated in all cases. There were no complications derived from the ablation. Conclusion: The association of ablation techniques with vertebral cementation is a safe technique that significantly improves the patient's pain and can help control the disease.(AU)

[Translated article] Tumor ablation and vertebral augmentation in the treatment of vertebral metastases: A multicenter study / Ablación tumoral y cementación en el tratamiento de las metástasis vertebrales. Estudio multicéntrico

Introducción: El tratamiento de las fracturas vertebrales metastásicas sin compresión neural se realiza con técnicas percutáneas de cementación. El aumento de presión intratumoral por estas técnicas puede enviar células tumorales al torrente sanguíneo. Para evitar esa diseminación y mejorar el tratamiento del dolor se han introducido las técnicas de ablación que permitirían crear una cavidad en el tumor previo a la cementación o directamente necrosar la metástasis cuando el tamaño es pequeño. Material: Presentamos la experiencia con la ablación de dos hospitales y dos técnicas de ablación distintas. El primer grupo usó la ablación por radiofrecuencia (ARF) en 14 pacientes (26 vértebras) de los cuales en cuatro se asoció una artrodesis vertebral. El segundo grupo usó la ablación por microondas (AMO); 93 pacientes (129 lesiones) sin asociar instrumentación vertebral. Resultados: En el grupo de ARF la mejoría del dolor en la escala visual analógica (EVA) fue de 7,7 a 2,6 a las seis semanas. No hubo complicaciones derivadas de la ablación. En la mayoría de los casos se asoció la cementación. En el grupo de AMO la mejoría del dolor en EVA pasó de 6,8 a 1,7 a las seis semanas. En todos los casos se asoció la cementación. No hubo complicaciones derivadas de la ablación. Conclusiones: La asociación de las técnicas de ablación a la cementación vertebral es una técnica segura, que permite mejorar notablemente el dolor del paciente y puede ayudar al control de la enfermedad.(AU)

Introduction: Treatment of metastatic vertebral fractures without neural compression is performed with percutaneous cementation techniques. The increase in intratumoral pressure by these techniques can send tumor cells into the bloodstream. To prevent this dissemination and improve pain treatment, ablation techniques have been introduced that would allow the creation of a cavity in the tumor prior to cementation or directly necrosing the metastasis when its size is small. Material: We present the experience with ablation of two hospitals and two different ablation techniques. The first group used radiofrequency ablation (A) in 14 patients (26 vertebrae), 4 of whom underwent vertebral arthrodesis. The second group used microwave ablation (B) in 93 patients (129 lesions) without associated vertebral instrumentation. Results: In group A pain improvement in VAS was 7.7–2.6 at 6 weeks. There were no complications derived from the ablation. In most cases cementation was associated. In the group B pain improvement in VAS went from 6.8–1.7 at 6 weeks. Cementation was associated in all cases. There were no complications derived from the ablation. Conclusion: The association of ablation techniques with vertebral cementation is a safe technique that significantly improves the patient's pain and can help control the disease.(AU)

Epidemiología y clínica de las metástasis vertebrales / Epidemiology and clinic of vertebral metastasis

El cáncer es en España la segunda causa de muerte en mujeres (22%) y la primera en varones (31%). En este capítulo describimos los tipos más frecuentes de metástasis raquídeas, sus localizaciones más habituales dentro de la columna vertebral, así como su comportamiento clínico. Analizamos también los cuadros neurológicos más comúnmente asociados a las metástasis de columna: compresión radicular, compresión medular, cauda equina y afectación medular.(AU)

Cancer is in Spain the second cause of death in women (22%) and the first in men (31%). In this chapter we describe the most frequent types of spinal metastases, their most frequent locations within the spine, as well as their clinical behavior. We also analyze the neurological conditions most frequently associated with spinal metastases: root compression, spinal cord compression, cauda equina, and spinal cord involvement.(AU)

[Translated article] Epidemiology and clinic of vertebral metastasis / Epidemiología y clínica de las metástasis vertebrales

El cáncer es en España la segunda causa de muerte en mujeres (22%) y la primera en varones (31%). En este capítulo describimos los tipos más frecuentes de metástasis raquídeas, sus localizaciones más habituales dentro de la columna vertebral, así como su comportamiento clínico. Analizamos también los cuadros neurológicos más comúnmente asociados a las metástasis de columna: compresión radicular, compresión medular, cauda equina y afectación medular.(AU)

Cancer is in Spain the second cause of death in women (22%) and the first in men (31%). In this chapter we describe the most frequent types of spinal metastases, their most frequent locations within the spine, as well as their clinical behavior. We also analyze the neurological conditions most frequently associated with spinal metastases: root compression, spinal cord compression, cauda equina, and spinal cord involvement.(AU)

Combined radiomics of primary tumour and bone metastasis improve the prediction of EGFR mutation status and response to EGFR-TKI therapy for NSCLC.

PURPOSE: To develop radiomics models of primary tumour and spinal metastases to predict epidermal growth factor receptor (EGFR) mutations and therapeutic response to EGFR-tyrosine kinase inhibitor (TKI) in patients with metastatic non-small-cell lung cancer (NSCLC). METHODS: We enrolled 203 patients with spinal metastases between December 2017 and September 2021, classified as patients with the EGFR mutation or EGFR wild-type. All patients underwent thoracic CT and spinal MRI scans before any treatment. Radiomics analysis was performed to extract features from primary tumour and metastases images and identify predictive features with the least absolute shrinkage and selection operator. Radiomics signatures (RS) were constructed based on primary tumour (RS-Pri), metastases (RS-Met), and in combination (RS-Com) to predict EGFR mutation status and response to EGFR-TKI. Receiver operating characteristic (ROC) curve analysis with 10-fold cross-validation was applied to assess the performance of the models. RESULTS: To predict the EGFR mutation status, the RS based on the combination of primary tumour and metastases improved the prediction AUCs compared to those based on the primary tumour or metastasis alone in the training (RS-Com-EGFR: 0.927) and validation (RS-Com-EGFR: 0.812) cohorts. To predict response to EGFR-TKI, the developed RS based on combined primary tumour and metastasis generated the highest AUCs in the training (RS-Com-TKI: 0.880) and validation (RS-Com-TKI: 0.798) cohort. CONCLUSIONS: Primary NSCLC and spinal metastases can provide complementary information to predict the EGFR mutation status and response to EGFR-TKI. The developed models that integrate primary lesions and metastases may be potential imaging markers to guide individual treatment decisions.

Conversion in a Resectable Tumor after Denosumab Neoadjuvant in a Large Dorsal Giant Cells Tumor: A Case Report and a Literature Review.

Giant cell tumors of bone are a rare entity, usually occurring in young patients and characteristically arising in the long bones. The spinal location is rare and usually presents with pain and/or neurological symptoms. The treatment of choice is surgery. Treatment with Denosumab, a bisphosphonate inhibitor of RANK-L, which is highly expressed in these tumors, has shown extensive activity in unresectable patients or those undergoing incomplete surgery. Preoperative treatment with this drug is gaining increasing interest, as its high potency in tumor reduction in this subtype of neoplasm has allowed resectability in selected patients. We present the case of a young patient with a large spinal tumor who, after neoadjuvant Denosumab, underwent complete en bloc surgery with clean margins and a great pathological response.

Biomaterials-enhanced bioactive agents to efficiently block spinal metastases of cancers.

The spine is the most common site of bone metastases, as 20%-40% of cancer patients suffer from spinal metastases. Treatments for spinal metastases are scarce and palliative, primarily aiming at relieving bone pain and preserving neurological function. The bioactive agents-mediated therapies are the most effective modalities for treating spinal metastases because they achieve systematic and specific tumor regression. However, the clinical applications of some bioactive agents are limited due to the lack of targeting capabilities, severe side effects, and vulnerability of drug resistance. Fortunately, advanced biomaterials have been developed as excipients to enhance these treatments, including chemotherapy, phototherapy, magnetic hyperthermia therapy, and combination therapy, by improving tumor targeting and enabling sustaining and stimuli-responsive release of various therapeutic agents. Herein, the review summarizes the development of biomaterials-mediated bioactive agents for enhanced treatments of spinal metastases and predicts future research trends.

Efficacy and safety of erythropoietin in isolated spinal metastasis patients with total en bloc spondylectomy surgery: a case-control study.

OBJECTIVE: The purpose of our study is to identify the effect of short-term and high-dose use of erythropoietin (EPO) in spinal isolated metastatic patients with Total en bloc spondylectomy (TES) surgery by assessing hematological parameters, transfusion volume, postoperative complications, recurrence-free survival (RFS), and overall survival (OS). METHODS: From January 2015 and January 2022, 93 isolated spinal metastasis patients were selected and separated into 2 groups based on the treatment method used (EPO + TXA (Tranexamic acid) group, n = 47; and TXA group, n = 46). Indexes for evaluation included hemoglobin (Hb), hematocrit (Hct), red blood cells (RBC), RFS, OS, postoperative complications, postoperative Frankel Grade, drainage volume, transfusion rate, and mean units transfused. RESULTS: The average follow-up duration was 38.13 months. There was no significant difference (P > 0.05) in RFS, OS, postoperative complications, postoperative Frankel Grade, drainage volume, and transfusion rate between the two groups. However, patients in EPO + TXA group have significantly higher Hb, Hct, and RBC values than those in the TXA group on postoperative days 1, 2, 3, and 5. Moreover, the mean transfusion volume in EPO + TXA group was significantly lower than those in the TXA group (P = 0.011). CONCLUSIONS: Perioperative short-term and high-dose administration of EPO could improve the anemia-related hematological parameters and reduce the requirement for blood transfusion without increasing the risk of deep vein thrombosis and tumor progression in solitary spinal metastatic patients with TES surgery.

Dual-Modal Imaging and Synergistic Spinal Tumor Therapy Enabled by Hierarchical-Structured Nanofibers with Cascade Release and Postoperative Anti-adhesion.

Most treatments for spinal cancer are accompanied by serious side effects including subsequent tumor recurrence, spinal cord compression, and tissue adhesion, thus a highly effective treatment is crucial for preserving spinal and neurological functionalities. Herein, trilayered electrospun doxorubicin@bovine serum albumin/poly(ε-caprolactone)/manganese dioxide (DOX@BSA/PCL/MnO2) nanofibers with excellent antiadhesion ability, dual glutathione/hydrogen peroxide (GSH/H2O2) responsiveness, and cascade release of Mn2+/DOX was fabricated for realizing an efficient spinal tumor therapy. In detail, Fenton-like reactions between MnO2 in the fibers outermost layer and intra-/extracellular glutathione within tumors promoted the first-order release of Mn2+. Then, sustained release of DOX from the fibers' core layer occurred along with the infiltration of degradation fluid. Such release behavior avoided toxic side effects of drugs, regulated inflammatory tumor microenvironment, amplified tumor elimination efficiency through synergistic chemo-/chemodynamic therapies, and inhibited recurrence of spinal tumors. More interestingly, magnetic resonance and photoacoustic dual-modal imaging enabled visualizations of tumor therapy and material degradation in vivo, achieving rapid pathological analysis and diagnosis. On the whole, such versatile hierarchical-structured nanofibers provided a reference for rapid and potent theranostic of spinal cancer in future clinical translations.

Precisely Targeted Nano-Controller of PD-L1 Level for Non-Small Cell Lung Cancer Spinal Metastasis Immunotherapy.

Although immune checkpoint inhibitors (ICIs) have been widely applied to treat non-small cell lung cancer (NSCLC), a significant proportion of patients, especially those with spinal metastasis (NSCLC-SM), are insensitive to anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) ICIs. A drug delivery nano-controller of PD-L1 that targets NSCLC-SM can solve this problem, however, none have been developed to date. In this study, it is shown that integrin ß3 (ß3-int) is strongly upregulated in NSCLC-SM. Its inhibitor RGDyK promotes PD-L1 ubiquitination, indicating the potential application of RGDyK as a new PD-L1 inhibitor in nano-controller and a targeting peptide for NSCLC-SM treatment. According to the synergistic effect of photodynamic therapy and ICIs on T-cell activation through the release of tumor antigens, RGDyK-modified and zinc protoporphyrin (ZnPP)-loaded mesoporous silicon nanoparticles (ZnPP@MSN-RGDyK) are fabricated. The ZnPP@MSN-RGDyK nanoparticles precisely target ß3-int to inhibit PD-L1, exhibiting high photodynamic therapy efficiency, and excellent immunotherapeutic effects in an NSCLC-SM mouse model. Collectively, the findings indicate that ZnPP@MSN-RGDyK is a promising immunotherapeutic agent for treating NSCLC-SM.

Prolonged durability of extensive contiguous spinal metastasis stabilization in non-small cell lung cancer patients receiving targeted therapy: two case reports and a literature review.

MINI-ABSTRACT: In this report, we present two cases of contiguous spinal metastatic disease in non-small cell lung cancer patients who achieved prolonged survival and stable spinal fixation after treatment with EGFR TKIs.

Siglec15 Checkpoint Blockade for Simultaneous Immunochemotherapy and Osteolysis Inhibition in Lung Adenocarcinoma Spinal Metastasis via a Hollow Nanoplatform.

Low responsiveness to anti-programmed death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) for solid tumors indicates the presence of other immunosuppressive pathways. Siglec15, a newly discovered immune checkpoint, has been reported to repress immune responses in the tumor microenvironment (TME) and regulate osteoclast differentiation. However, the role of Siglec15 in the treatment for bone metastasis remains unclear. Herein, Siglec15 shows significantly higher expression in lung adenocarcinoma spinal metastasis (LUAD-SM) than in para-cancerous spinal tissues and primary LUAD. Subsequently, a TME-responsive hollow MnO2 nanoplatform (H-M) loaded with Siglec15 siRNA and cisplatin (H-M@siS15/Cis) is developed, and the surface is modified with an aspartic acid octapeptide (Asp8 ), thus allowing H-M to target spinal metastasis. High drug-loading capacity, good biocompatibility, effective tumor accumulation, and efficient Siglec15 silencing are demonstrated. Furthermore, the nanoparticles could reverse immunosuppression caused by tumor cells and tumor-associated macrophages (TAMs) and inhibit osteoclast differentiation via Siglec15 downregulation in vitro. In a LUAD-SM mouse model, H-M@siS15/Cis-Asp8 exhibits superior therapeutic efficacy via synergetic immunochemotherapy and osteolysis inhibition. Taken together, this single nanoplatform reveals the therapeutic potential of the new immune checkpoint Siglec15 in LUAD-SM and provides a strategy to treat this disease.

Efficacy Evaluation of Zoledronic Acid Combined with Chemotherapy in the Treatment of Lung Cancer Spinal Metastases on Computed Tomography Images on Intelligent Algorithms.

To analyze the effectiveness and safety of zoledronic acid combined with chemotherapy for lung cancer spinal metastases, 96 patients with lung cancer spinal metastases were averagely classified into the experimental group (gemcitabine, cisplatin, and zoledronic acid) and the control group (gemcitabine and cisplatin). An optimized noise variance estimation algorithm (OMAPB) was proposed based on the maximum a posteriori Bayesian method (MAPB), and the algorithm was applied to the patient's computed tomography (CT) scan. The results indicated that in terms of curative effect, the number of complete remission (CR), partial remission (PR) cases, effective rate, and clinical benefit rate of the test group was significantly higher than those of the control group. The number of progress disease (PD) cases was significantly lower than that of the control group (P < 0.05). The disease progression time of the test group patients was 6.2 months, and the disease progression time of the control group patients was 3.7 months (P < 0.05). The test group patients had 8 cases of bone marrow suppression and gastrointestinal reactions after treatment. In the test group, there were 8 cases of bone marrow suppression, 9 cases of gastrointestinal reaction, 3 cases of fever, 4 cases of pain, and 2 cases of hair loss. The patients in the control group were complicated with bone marrow suppression in 14 cases, gastrointestinal reaction in 17 cases, fever in 5 cases, pain in 4 cases, and hair loss in 6 cases. The difference was statistically significant (P < 0.05). It showed that zoledronic acid combined with chemotherapy could effectively improve the treatment efficiency and clinical benefit rate of patients with lung cancer spinal metastases, prolong the progression of the disease, reduce the degree of bone tissue damage, and would not increase chemotherapy adverse events.

Total neurological recovery after surgical decompression and treatment with denosumab of large unresectable spinal giant cell tumour expanding to mediastinum.

There is a controversy over the medical treatment of unresectable spinal giant cell tumour (GCT) regarding dosing and duration. We studied a spinal GCT case that had expanded to the thoracic spinal canal and mediastinum and was successfully treated by surgical decompression and denosumab. A woman in her 30s presented with weakness in both the lower extremities. MRI revealed a large tumour in the posterior mediastinum expanding from the thoracic vertebrae (T3-6), which compressed the spinal cord. The patient underwent urgent spinal decompression with instrumentation and her tissue was sent for a pathology study. Histologically and immunohistochemistry confirmed the diagnosis of GCT. Since it was an unresectable tumour, this patient was treated with denosumab. Her neurological problem resolved after 6 months of treatment. After 4 years of follow-up, the patient displayed no further progression and no side effects from long-term denosumab usage.

Hybrid Mesoporous MnO2-Upconversion Nanoparticles for Image-Guided Lung Cancer Spinal Metastasis Therapy.

Upconversion nanoparticles (UCNPs) and MnO2 composite materials have broad prospects in biological applications due to their near-infrared (NIR) imaging capability and tumor microenvironment-responsive features. Nevertheless, the synthesis of such composite nanoplatforms still faces many hurdles such as redundant processing and uneven coatings. Here, we explored a simple, rapid, and universal method for precisely controlled coating of mesoporous MnO2 (mMnO2) using poly(ethylene imine) as a reducing agent and potassium permanganate as a manganese source. Using this strategy, a mMnO2 shell was successfully coated on UCNPs. We further modified the mMnO2-coated UCNPs (UCNP@mMnO2) with a photosensitizer (Ce6), cisplatin drug (DSP), and tumor targeting pentapeptide (TFA) to obtain a nanoplatform UCNP/Ce6@mMnO2/DSP-TFA for treating spinal metastasis of nonsmall cell lung cancer (NSCLC-SM). The utilization of both upconversion and downconversion luminescence of UCNPs with different NIR wavelengths can avoid the simultaneous initiation of NIR-II in vivo imaging and tumor photodynamic therapy, thus reducing damage to normal tissues. This platform achieved a high synergistic effect of photodynamic therapy and chemotherapy. This leads to beneficial antitumor effects on the therapy of NSCLC-SM.