Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC. Conclusion. Tumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients. Cite this article: Bone Jt Open 2024;5(4):350–360

Aims. Patients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas. Methods. We collected data on 22 patients with DTC (16 follicular and six papillary carcinomas) and one patient with medullary carcinoma who underwent complete surgical resection of SMs at our institution between July 1992 and July 2017, with a minimum postoperative follow-up of five years. The cancer-specific survival (CSS) from the first spinal metastasectomy to death or the last follow-up was determined using Kaplan-Meier analysis. Potential factors associated with survival were evaluated using the log-rank test. We analyzed the clinical parameters and outcome data, including pre- and postoperative disability (Eastern Cooperative Oncology Group PS 3), lung and non-spinal bone metastases, and history of radioiodine and kinase inhibitor therapies. Results. Lung and other bone metastases at the time of surgery were observed in ten and eight patients, respectively. Three patients experienced local tumour recurrences at the operated site. The five- and ten-year CSS rates in the 22 patients with DTC were 77% and 52%, respectively. Pre- and postoperative disability and operative site tumour recurrence were identified as risk factors for short postoperative survival. Conclusion. Metastasectomy for resectable SM from DTC yielded favourable results and has the potential to improve survival. Cite this article: Bone Joint J 2023;105-B(5):575–582

Bone turnover and microdamage are impacted by skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This study aimed to establish an understanding of microdamage accumulation and load to failure in healthy and osteolytic vertebrae following cancer treatment (stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX)). Forty-two 6-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo) were studied; 22 were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Animals were randomly assigned to four groups: untreated (healthy=5, osteolytic=6), SBRT on day 14 (healthy=6, osteolytic=6), ZA on day 7 (healthy=4, osteolytic=5), and DTX on day 14 (healthy=5, osteolytic=5). Animals were euthanized on day 21. L1-L3 motion segments were compression loaded to failure and force-displacement data recorded. T13 vertebrae were stained with BaSO. 4. and µCT imaged (90kVp, 44uA, 4.9µm) to visualize microdamage location and volume. Damage volume fraction (DV/BV) was calculated as the ratio of BaSO. 4. to bone volume. Differences in mean load-to-failure were compared using three-way ANOVA (disease status, treatment, cells injected). Differences in mean DV/BV between treatment groups were compared using one-way ANOVA. Treatment had a significant effect on load-to-failure (p=0.004) with ZA strengthening the healthy and osteolytic vertebrae. Reduced strength post SBRT seen in the metastatic (but not the healthy) group may be explained by greater tumor involvement secondary to higher cell injection concentrations. Untreated metastatic samples had higher DV/BV (16.25±2.54%) compared to all treatment groups (p<0.05) suggesting a benefit of treatment to bone quality. Focal and systemic cancer treatments were shown to effect load-to-failure and microdamage accumulation in healthy and osteolytic vertebrae. Developing a better understanding of how treatments effect bone quality and mechanical stability is critical for effective management of patients with spinal metastases

The April 2023 Spine Roundup³⁶⁰ looks at: Percutaneous transforaminal endoscopic discectomy versus microendoscopic discectomy; Spine surgical site infections: a single debridement is not enough; Lenke type 5, anterior, or posterior: systematic review and meta-analysis; Epidural steroid injections and postoperative infection in lumbar decompression or fusion; Noninferiority of posterior cervical foraminotomy versus anterior cervical discectomy; Identifying delays to surgical treatment for metastatic disease; Cervical disc replacement and adjacent segment disease: the NECK trial; Predicting complication in adult spine deformity surgery.

Vertebral metastases are the most common type of malignant lesions of the spine. Although this tumour is still considered incurable and standard treatments are mainly palliative, the standard approach consists in surgical resection, which results in the formation of bone gaps. Hence, scaffolds, cements and/or implants are needed to fill the bone lacunae. Here, we propose a novel approach to address spinal metastases recurrence, based on the use of anti-tumour metallic-based nanostructured coatings. Moreover, for the first time, a gradient microfluidic approach is proposed for the screening of nanostructured coatings having anti-tumoral effect, to determine the optimal concentration of the metallic compound that permits selective toxicity towards tumoral cells. Coatings are based on Zinc as anti-tumour agent, which had been never explored before for treatment of bone metastases. The customized gradient generating microfluidic chip was designed by Autodesk Inventor and fabricated from a microstructured mould by using replica moulding technique. Microstructured mould were obtained by micro-milling technique. The chip is composed of a system of microfluidic channels generating a gradient of 6 concentrations of drug and a compartment with multiple arrays of cell culture chambers, one for each drug concentration. The device is suitable for dynamic cultures and in-chip biological assays. The formation of a gradient was validated using a methylene blue solution and the cell loading was successful. Preliminary biological data on 3D dynamic cultures of stromal cells (bone-marrow mesenchymal stem cells) and breast carcinoma cells (MDA-MB-231) were performed in a commercial microfluidic device. Results showed that Zn eluates had a selective cytotoxic effect for tumoral cells. Indeed, cell migration and cell replication of treated tumoral cells was inhibited. Moreover, the three-dimensionality of the model strongly affected the efficacy of Zn eluates, as 2D preliminary experiments showed a high cytotoxic effect of Zn also for stromal cells, thus confirming that traditional screening tests on 2D cultured cells usually lead to an overestimation of drug efficacy and toxicity. Based on preliminary data, the customized platform could be considered a major advancement in cancer drug screenings as it also allows the rapid and efficient screening of biomaterials having antitumor effect

Aims

The incidence of bone metastases is between 20% to 75% depending on the type of cancer. As treatment improves, the number of patients who need surgical intervention is increasing. Identifying patients with a shorter life expectancy would allow surgical intervention with more durable reconstructions to be targeted to those most likely to benefit. While previous scoring systems have focused on surgical and oncological factors, there is a need to consider comorbidities and the physiological state of the patient, as these will also affect outcome. The primary aim of this study was to create a scoring system to estimate survival time in patients with bony metastases and to determine which factors may adversely affect this.

Aims. To evaluate the perioperative complications associated with total en bloc spondylectomy (TES) in patients with spinal tumours, based on the extent and level of tumour resection. Methods. In total, 307 patients who underwent TES in a single centre were reviewed retrospectively. There were 164 male and 143 female patients with a mean age at the time of surgery of 52.9 years (SD 13.3). A total of 225 patients were operated on for spinal metastases, 34 for a malignant primary tumour, 41 for an aggressive benign tumour, and seven with a primary of unknown origin. The main lesion was located in the thoracic spine in 213, and in the lumbar spine in 94 patients. There were 97 patients who underwent TES for more than two consecutive vertebrae. Results. Major and minor perioperative complications were observed in 122 (39.7%) and 84 (27.4%) patients respectively. The breakdown of complications was as follows: bleeding more than 2,000 ml in 60 (19.5%) patients, hardware failure in 82 (26.7%), neurological in 46 (15.0%), surgical site infection in 23 (7.5%), wound dehiscence in 16 (5.2%), cerebrospinal fluid leakage in 45 (14.7%), respiratory in 52 (16.9%), cardiovascular in 11 (3.6%), digestive in 19 (6.2%)/ The mortality within two months of surgery was four (1.3%). The total number of complications per operation were 1.01 (SD 1.0) in the single vertebral resection group and 1.56 (SD 1.2) in the group with more than two vertebral resections. Cardiovascular and respiratory complications, along with hardware failure were statistically higher in the group who had more than two vertebrae resected. Also, in this group the amount of bleeding in patients with a lumbar lesion or respiratory complication in patients with a thoracic lesion, were statistically higher. Multivariate analysis showed that using a combined anterior and posterior approach, when more than two vertebral resections were significant independent factors. Conclusion. The characteristics of perioperative complications after TES were different depending on the extent and level of the tumour resection. In addition to preoperative clinical and pathological factors, it is therefore important to consider these factors in patients who undergo en bloc resection for spinal tumours. Cite this article: Bone Joint J 2021;103-B(5):976–983

Aims. With recent progress in cancer treatment, the number of advanced-age patients with spinal metastases has been increasing. It is important to clarify the influence of advanced age on outcomes following surgery for spinal metastases, especially with a focus on subjective health state values. Methods. We prospectively analyzed 101 patients with spinal metastases who underwent palliative surgery from 2013 to 2016. These patients were divided into two groups based on age (< 70 years and ≥ 70 years). The Eastern Cooperative Oncology Group (ECOG) performance status (PS), Barthel index (BI), and EuroQol-5 dimension (EQ-5D) score were assessed at study enrolment and at one, three, and six months after surgery. The survival times and complications were also collected. Results. In total, 65 patients were aged < 70 years (mean 59.6 years; 32 to 69) and 36 patients were aged ≥ 70 years (mean 75.9 years; 70 to 90). In both groups, the PS improved from PS3 to PS1 by spine surgery, the mean BI improved from < 60 to > 80 points, and the mean EQ-5D score improved from 0.0 to > 0.7 points. However, no significant differences were found in the improvement rates and values of the PS, BI, and EQ-5D score at any time points between the two groups. The PS, BI, and EQ-5D score improved throughout the follow-up period in approximately 90% of patients in each group. However, the improved PS, BI, and EQ-5D scores subsequently deteriorated in some patients, and the redeterioration rate of the EQ-5D was significantly higher in patients aged ≥ 70 than < 70 years (p = 0.027). Conclusion. Palliative surgery for spinal metastases improved the PS, activities of daily living, and quality of life, regardless of age. However, clinicians should be aware of the higher risk of redeterioration of the quality of life in advanced-age patients. Cite this article: Bone Joint J 2020;102-B(12):1709–1716

Spinal metastases are seen in 10–30% of cancer patients. Twenty percent of these metastases occur in the lumbo-sacral spine. Lumbo-sacral spine has different mechanical properties and encloses the cauda equina. Few studies took interest in this spinal segment. The objective of this study is to evaluate prognostic factors of lumbo-sacral spinal metastasis treated in our center. We retrospectively reviewed 376 patients who were operated in our center from 2010 to 2018. Eighty-nine patients presented lumbo-sacral metastases and thus were included. Data collected included age, smoking, tumor histology, American spinal injury association (ASIA) score, modified Tokuhashi score, modified Bauer score, ambulation status and adjuvant treatment. The mean population age was 60.9 years old (35–85). The tumor histology was predominantly lung (19 patients, 21.3%), breast (13 patients, 14.6%), kidney (11 patients, 12.4%) and prostate (9 patients 10.1%). Twenty-two patients (24.7%) were unable to walk preoperatively. Seventy-nine patients (88.8%) underwent a posterior open approach with corpectomy in 65 patients (73%). Eighteen patients regained ambulation post-operatively (81.8%). The mean survival was 24.03 months (CI95% 17,38–30,67, Range 0–90) and the median of survival was 9 months (CI95% 4.38–13.62). Better preoperative ASIA score had a significant favorable effect (p=0.03) on survival. Patients who regained their ability to walk had better survival (25.1 months (CI95% 18.2–32) VS 0.5 months (CI95% 0–1.1). Postoperative radiotherapy had a benefic effect on survival (p=0.019): Survival Increased from 10.5 months (CI95% 2.4–18.7) to 27.6 months (CI95% 19.5–35.8). The modified Tokuhashi and the modified Bauer scores underestimated the survival of the patients with lumbosacral metastases. Lumbosacral spinal metastases has better survival than expected by Tokuhashi and Bauer score. Surgical procedure have an important impact on survival and the ability to walk

National Institute of Clinical Excellence guidelines on Metastatic Spinal Cord Compression recommend urgent consideration of patients with spinal metastases and imaging evidence of structural spinal failure with spinal instability for surgery to stabilise the spine and prevent Metastatic Spinal Cord Compression. We aimed to compare neurological outcomes of patients managed operatively and non-operatively. Prospective collection of 397 patients' data over a 4-year period. Males represented 59.2% of patients. Median age was 69 years. Non-operative intervention in 62.2% of patients. Prostate, lung, Breast, Myeloma, Renal Cell Carcinoma and Lymphoma accounted for over 75% of all primary tumours (n=305). Median Length of hospital stay was longer in the operative group of 15 days compared to 10 days in the non-operative group (p<0.0001). Patients who were ambulating on presentation maintained their ambulation in 70.2% of cases in the operative group compared to 90.9% in the non-operative group (p<0.0001). However, upon discharge 41% of patients managed operatively were ambulatory compared to the non-operative group rate of 36.5% (p<0.0001). In Prostate, Breast, Myeloma, RCC and Lymphoma 100% of patients managed non-operatively maintained ambulation. Lung primaries managed operatively had an 80% chance of maintaining ambulation compared to 76.9% in the non-operative group (p<0.05). A higher proportion of patients managed non-operatively maintained ambulation than those managed operatively. With operative intervention, more patients regained ambulatory status. Whilst we have mainly focused on ambulatory status in this paper there are other factors to consider including pain relief and spinal stability which may be an indication for surgical intervention

Aims

This study aimed to evaluate the incidence and prognosis of patients with spinal metastasis as the initial manifestation of malignancy (SM-IMM).

Photodynamic therapy (PDT) uses the strong cytotoxicity of singlet oxygen and hyperthermia produced by irradiating excitation light on a photosensitizer. The phototoxic effects of indocyanine green (ICG) and near-infrared light (NIR) have been studied in different types of cancer cells. Plasma proteins bind strongly to ICG, followed by rapid clearance by the liver, resulting in no tumor-selective accumulation after systemic administration. Kimura et al. have proposed using a novel nanoparticle labeled with ICG (ICG-lactosome) that has tumor selective accumulation owing to enhanced permeability and retention (EPR) effect. In this study, we investigated the efficacy of PDT using ICG-lactosome and NIR for a bone metastatic mouse model of breast cancer. Cells from the human breast cancer cell line, MDA-MB-231 were injected into the right tibia of 26 anesthetized BALB/C nu/nu mice at a concentration. The mice were then randomly divided into three groups: the PDT group (n = 9), the laser (laser irradiation only) group (n = 9), and the control group (n = 8). PDT was performed thrice (7, 21, 35 days after cell inoculation) following ICG-lactosome administration via the tail vein 24 hours before irradiation. The mice were percutaneously irradiated with an 810-nm medical diode laser for 10 min. In the laser group, mice were irradiated following saline administration 24 hours before irradiation. Radiographic analysis was performed for 49 days after cell inoculation. The area of osteolytic lesion was quantified. The right hind legs of 3 mice were amputated 24 hours after the third treatment. Histological analysis was performed using hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining of sagittal sections. The data was analyzed using Tukey-Kramer post-hoc test. P-value of <0.05 was considered significant. X-ray on day 49 of the three groups are considered. The area of osteolytic lesion in the PDT group (7.9 ± 1.2 mm. 2. : mean ± SD) was significantly smaller than that of the control (11.4 ± 1.4 mm. 2. ) and laser (11.9 ± 1.2 mm. 2. ) groups. In histological findings, we observed many TUNEL-positive cells in the metastatic tissue 24 hours after PDT. In the control and laser groups, TUNEL-positive cells were occasionally observed. We have previously reported the effect of ICG-lactosome-enhanced PDT on the cytotoxicity of human breast cancer cells in vitroand on the delay of paralysis in a rat spinal metastasis model. In this study, we demonstrated the inhibitory effect of ICG-lactosome-enhanced PDT on bone destruction caused by human breast cancer cells in vivo. This PDT induced apoptosis and necrosis in the tumor cells. Intralesional resection is often performed for spinal metastases in an emergency. The residual tumor may regrow and cause neurological deficits. We believe that ICG-lactosome-enhanced PDT can decrease the rate of local recurrence through reduction of the residual tumor. PDT with ICG-lactosome and NIR had an inhibitory effect on the growth of bone metastasis of a human breast cancer