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.

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.

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.

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.

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.

Metastatic chordoma with pancreatic disease and response to imatinib.

A 45-year-old woman presented with a left-sided neck swelling following treatment a year prior for cervical spine chordoma. She had initially been managed surgically with a cervical vertebrectomy and a course of proton beam therapy. Although there had been a degree of residual tissue, her disease remained stable radiologically and clinically. Repeat MRI demonstrated an increasing left paravertebral mass and a head of pancreas metastasis, which shared pathological characteristics with chordoma. Given the advanced metastatic nature of her disease, imatinib was offered with a palliative intent. While waiting for treatment she developed a spinal cord compression, managed with radiotherapy. She commenced imatinib and her disease remained stable for 9 months before progressing clinically and radiologically. This case demonstrates an unusual pattern of metastatic chordoma and provides further rationale for imatinib in such patients.

Adjunctive Topical Tranexamic Acid for Blood Salvage Does Not Reduce Postoperative Blood Loss Compared with Placebo in Patients Who Undergo Palliative Decompressive Spinal Metastasis Surgery: A Randomized Controlled Trial.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To evaluate the efficacy of adjunctive topical tranexamic acid (tTXA) in reducing postoperative blood loss and packed red cell (PRC) transfusion in patients who underwent palliative decompressive spinal metastasis surgery for malignant epidural spinal cord compression. SUMMARY OF BACKGROUND DATA: Palliative decompressive spinal metastasis surgery is associated with massive postoperative blood loss and increased transfusion rate. tTXA reduces blood loss in traumatic or degenerative spinal surgery; however, the role of topical TXA in decompressive spinal metastasis surgery remains controversial. METHOD: A total of 65 patients who underwent palliative decompressive thoracolumbar spinal metastasis surgery were included in this study. In 33 patients, 1 g of tTXA (20 mL) was soaked in an absorbable gelatin sponge and placed lateral to the decompressive site. The remaining 32 patients in the control group received the same procedures with normal saline at the same volume, instead of TXA. All of the patients received standard 1 g intravenous TXA, just before initiating the operation. The primary outcome was postoperative blood loss, and the secondary outcomes were postoperative PRC transfusion and complications. RESULTS: No differences were found in postoperative blood loss between tTXA and placebo group (P50 778 mL [IQR 347, 1,122 mL] versus P50 490 mL [IQR 295, 920 mL]; P = 0.238). The number of patients requiring postoperative PRC transfusion were quite similar in tTXA and placebo groups (PRC transfusion in 15 patients [45.45%] versus 16 patients [50%]; P = 0.585). No complications related to TXA and absorbable gelatin sponge were observed. CONCLUSION: We do not recommend tTXA as an adjunctive treatment for patients undergoing decompressive spinal metastasis surgery since it does not provide additional benefit to prophylactic intravenous TXA in postoperative blood loss and transfusion rate.Level of Evidence: 2.

Improvement in the Symptoms and VEGF Levels after Resection of an Extrame Dullary Spinal Tumor and Additional Chemotherapy in a Patient with Multiple Myeloma Complicated with POEMS Syndrome.

We herein report a case of multiple myeloma and polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome. The patient experienced exacerbated gait disturbance due to weakness and numbness in the lower limbs. Thoracic magnetic resonance imaging revealed an extramedullary tumor with spinal compression that required surgical resection. Plasmacytoma was diagnosed based on a biopsy. Radiation, betamethasone, and chemotherapy were therefore administered. Surgical removal of extramedullary tumors improved his symptoms, motor conduction velocity, and amplitude of the muscle action potential in the peroneal and tibial nerves, as shown by the nerve conduction study. Surgery also decreased the serum vascular endothelial growth factor levels. The patient required additional chemotherapy due to multiple myeloma and showed better outcomes nine months after discharge. The benefits of some treatments remain controversial due to the small number of patients. However, our findings reveal that an early diagnosis and comprehensive treatment may result in better outcomes in such patients.

Ligand-Dependent and Ligand-Independent Effects of Ephrin-B2-EphB4 Signaling in Melanoma Metastatic Spine Disease.

Tumor-endothelial cell interactions represent an essential mechanism in spinal metastasis. Ephrin-B2-EphB4 communication induces tumor cell repulsion from the endothelium in metastatic melanoma, reducing spinal bone metastasis formation. To shed further light on the Ephrin-B2-EphB4 signaling mechanism, we researched the effects of pharmacological EphB4 receptor stimulation and inhibition in a ligand-dependent/independent context. We chose a preventative and a post-diagnostic therapeutic window. EphB4 stimulation during tumor cell seeding led to an increase in spinal metastatic loci and number of disseminated melanoma cells, as well as earlier locomotion deficits in the presence of endothelial Ephrin-B2. In the absence of endothelial Ephrin-B2, reduction of metastatic loci with a later manifestation of locomotion deficits occurred. Thus, EphB4 receptor stimulation affects metastatic dissemination depending on the presence/absence of endothelial Ephrin-B2. After the manifestation of solid metastasis, EphB4 kinase inhibition resulted in significantly earlier manifestation of locomotion deficits in the presence of the ligand. No post-diagnostic treatment effect was found in the absence of endothelial Ephrin-B2. For solid metastasis treatment, EphB4 kinase inhibition induced prometastatic effects in the presence of endothelial Ephrin-B2. In the absence of endothelial Ephrin-B2, both therapies showed no effect on the growth of solid metastasis.

Camrelizumab plus Zoledronic Acid Showed Sustained Efficacy in a Patient with Cranial and Spinal Metastases from Lung Adenocarcinoma.

The role of anti-programmed cell death protein-1 (PD-1) antibody camrelizumab in brain metastases (BMs) from lung adenocarcinoma is uncertain. Herein, for the first time, we report the efficacy of camrelizumab in a patient with chemotherapy-refractory BMs from lung adenocarcinoma. A 49-year-old male non-smoker was admitted with cough and back pain. Primary lung adenocarcinoma with brain and spinal metastases was diagnosed. The specimen from CT-guided lung biopsy showed a positive expression of PD-L1 (~20%).The BMs were enlarged after first-line intravenous pemetrexed/cisplatin and zoledronic acid; whereas second-line camrelizumab demonstrated impressive complete remission of the BMs. The intracranial progression-free survival and overall survival of the patients since the start of the immunotherapy plan prolonged to more than 12 months and 20 months, respectively. In addition, we searched PubMed for relevant studies from inception to May 2020, and a total of 23 reports enrolling 1187 patients also indicated the promising efficacy of immunotherapy for BMs from lung cancer. However, more and better evidence is still needed before a definite conclusion could be drawn.