Efficacy and safety of SBRT for spine metastases: A systematic review and meta-analysis for preparation of an ESTRO practice guideline.

BACKGROUND AND PURPOSE: Advances in characterizing cancer biology and the growing availability of novel targeted agents and immune therapeutics have significantly changed the prognosis of many patients with metastatic disease. Palliative radiotherapy needs to adapt to these developments. In this study, we summarize the available evidence for stereotactic body radiotherapy (SBRT) in the treatment of spinal metastases. MATERIALS AND METHODS: A systematic review and meta-analysis was performed using PRISMA methodology, including publications from January 2005 to September 2021, with the exception of the randomized phase III trial RTOG-0631 which was added in April 2023. Re-irradiation was excluded. For meta-analysis, a random-effects model was used to pool the data. Heterogeneity was assessed with the I2-test, assuming substantial and considerable as I2 > 50 % and I2 > 75 %, respectively. A p-value < 0.05 was considered statistically significant. RESULTS: A total of 69 studies assessing the outcomes of 7236 metastases in 5736 patients were analyzed. SBRT for spine metastases showed high efficacy, with a pooled overall pain response rate of 83 % (95 % confidence interval [CI] 68 %-94 %), pooled complete pain response of 36 % (95 % CI: 20 %-53 %), and 1-year local control rate of 94 % (95 % CI: 86 %-99 %), although with high levels of heterogeneity among studies (I2 = 93 %, I2 = 86 %, and 86 %, respectively). Furthermore, SBRT was safe, with a pooled vertebral fracture rate of 9 % (95 % CI: 4 %-16 %), pooled radiation induced myelopathy rate of 0 % (95 % CI 0-2 %), and pooled pain flare rate of 6 % (95 % CI: 3 %-17 %), although with mixed levels of heterogeneity among the studies (I2 = 92 %, I2 = 0 %, and 95 %, respectively). Only 1.7 % of vertebral fractures required surgical stabilization. CONCLUSION: Spine SBRT is characterized by a favorable efficacy and safety profile, providing durable results for pain control and disease control, which is particularly relevant for oligometastatic patients.

ESTRO clinical practice guideline: Stereotactic body radiotherapy for spine metastases.

BACKGROUND AND PURPOSE: Recent progress in diagnostics and treatment of metastatic cancer patients have improved survival substantially. These developments also affect local therapies, with treatment aims shifting from short-term palliation to long-term symptom or disease control. There is consequently a need to better define the value of stereotactic body radiotherapy (SBRT) for the treatment of spinal metastases. METHODS: This ESTRO clinical practice guideline is based on a systematic literature review conducted according to PRISMA standards, which formed the basis for answering four key questions about the indication and practice of SBRT for spine metastases. RESULTS: The analysis of the key questions based on current evidence yielded 22 recommendations and 5 statements with varying levels of endorsement, all achieving a consensus among experts of at least 75%. In the majority, the level of evidence supporting the recommendations and statements was moderate or expert opinion, only, indicating that spine SBRT is still an evolving field of clinical research. Recommendations were established concerning the selection of appropriate patients with painful spine metastases and oligometastatic disease. Recommendations about the practice of spinal SBRT covered technical planning aspects including dose and fractionation, patient positioning, immobilization and image-guided SBRT delivery. Finally, recommendations were developed regarding quality assurance protocols, including description of potential SBRT-related toxicity and risk mitigation strategies. CONCLUSIONS: This ESTRO clinical practice guideline provides evidence-based recommendations and statements regarding the selection of patients with spinal metastases for SBRT and its safe implementation and practice. Enrollment of patients into well-designed prospective clinical trials addressing clinically relevant questions is considered important.

Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes.

Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently found in patients suffering from chronic low-back pain. Marrow fibrosis is a hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other fibrotic bone marrow pathologies, yet their role in MC1 is unknown. The present study aimed to characterise MC1 BMSCs and hypothesised a pro-fibrotic role of BMSCs in MC1. BMSCs were isolated from patients undergoing lumbar spinal fusion from MC1 and adjacent control vertebrae. Frequency of colony-forming unit fibroblast (CFU-F), expression of stem cell surface markers, differentiation capacity, transcriptome, matrix adhesion, cell contractility as well as expression of pro-collagen type I alpha 1, α-smooth muscle actin, integrins and focal adhesion kinase (FAK) were compared. More CFU-F and increased expression of C-X-C-motif-chemokine 12 were found in MC1 BMSCs, possibly indicating overrepresentation of a perisinusoidal BMSC population. RNA sequencing analysis showed enrichment in extracellular matrix proteins and fibrosis-related signalling genes. Increases in pro-collagen type I alpha 1 expression, cell adhesion, cell contractility and phosphorylation of FAK provided further evidence for their pro-fibrotic phenotype. Moreover, a leptin receptor high expressing (LEPRhigh) BMSC population was identified that differentiated under transforming growth factor beta 1 stimulation into myofibroblasts in MC1 but not in control BMSCs. In conclusion, pro-fibrotic changes in MC1 BMSCs and a LEPRhigh MC1 BMSC subpopulation susceptible to myofibroblast differentiation were found. Fibrosis is a hallmark of MC1 and a potential therapeutic target. A causal link between the pro-fibrotic phenotype and clinical characteristics needs to be demonstrated.

Does neck pain as chief complaint influence the outcome of cervical total disc replacement?

PURPOSE: We investigated whether outcomes after cervical total disc replacement (cTDR) are influenced by preoperative neck pain as the chief complaint. METHODS: This was a retrospective study using data in our local spine surgery outcomes database, linked to EUROSPINE Spine Tango Registry. Patients completed questionnaires at baseline enquiring about the "chief complaint" [neck pain (NP), arm/shoulder pain (AP) or neurological deficits (ND)] and including the Core Outcome Measures Index (COMI); these were completed again at 24 months postoperatively, along with a rating of "global treatment outcome" (on a five-point scale, later dichotomized as "good" or "poor"). Differences in outcomes between the groups were examined using ANOVA. Multivariable regression analysis examined the effect of the chief pain location on 24-month outcomes, controlling for age, gender, comorbidity, baseline pain and COMI scores. RESULTS: One hundred and fifty-nine consecutive patients were included, with a chief complaint of NP in 31%, AP in 38% and ND in 31%. The chief complaint groups did not differ in relation to their baseline COMI scores or their reductions in score from before surgery to 24 months after surgery (reduction: NP group, 4.4 ± 2.9 points; AP group, 4.7 ± 2.7; ND group, 4.3 ± 2.9; p = 0.78). Similarly, the percentage of patients reporting a "good global treatment outcome" at 24 months postoperatively did not differ between the groups (NP, 79%; AP, 77%; ND, 85%; p = 0.64). The findings were consistent when controlling for possible confounders in multiple regression. CONCLUSIONS: Having neck pain as opposed to arm pain or neurological deficits as preoperative chief complaint had no significant impact on clinical outcome after cTDR. These slides can be retrieved under Electronic Supplementary Material.

Are preoperative sex-related differences of affective symptoms in primary brain tumor patients associated with postoperative histopathological grading?

Our objective was to explore the impact of the histopathological tumor type on affective symptoms before surgery among male and female patients with supratentorial primary brain tumors. A total of 44 adult patients were included in the study. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory. Additionally, clinical interviews, including the Hamilton Depression Rating Scale (HDRS), were conducted. The general function of patients was measured with the Karnofsky Performance Status scale (KPS). All measures were obtained before surgery and therefore before the final histopathological diagnosis. All self-rating questionnaires but not the HDRS, showed significantly higher scores in female patients. The functional status assessed with the KPS was lower in female patients and correlated to the somatic part of the BDI. We further found a tendency for higher HDRS scores in male patients with a WHO grade 4 tumor stage compared to female patients. This finding was supported by positive correlations between HDRS scores and WHO grade in male and negative correlations between HDRS scores and WHO grade in female patients. In conclusion the preoperative evaluation of affective symptoms with self-rating questionnaires in patients with brain tumors may be invalidated by the patient's functional status. Depression should be explored with clinical interviews in these patients. Sex differences of affective symptoms in this patient group may also be related to the malignancy of the tumor, but further studies are needed to disentangle this relationship.

Monitoring of the inflammatory response after aneurysmal subarachnoid haemorrhage in the clinical setting: review of literature and report of preliminary clinical experience.

BACKGROUND: Clinical and experimental studies showed a marked inflammatory response in aneurysmal subarachnoid haemorrhage (SAH), and it has been proposed to play a key role in the development of cerebral vasospasm (CVS). Inflammatory response and occurrence of CVS may represent a common pathogenic pathway allowing point of care diagnostics of CVS. Therefore, monitoring of the inflammatory response might be useful in the daily clinical setting of an ICU. The aim of the current report is to give a summary about factors contributing to the complex pathophysiology of inflammatory response in SAH and to discuss possible monitoring modalities. METHODS: Review and analysis of the existing literature and definition of own study protocols. RESULTS: In cerebrospinal fluid, interleukin (IL)-6 has been found to be significantly higher in patients with CVS during the peri-vasospasm period. While systemic inflammatory response syndrome, high C-reactive protein levels and leukocyte counts has been linked with the occurrence of CVS, less has been reported about cytokines levels in the jugular bulb of the internal jugular vein and in the peripheral blood. Preliminary evaluation of own data suggests, that IL-6 values in the peripheral blood and the arterio-jugular differences of IL-6 are increased with the inflammatory response after SAH. CONCLUSION: Monitoring of the inflammatory response, in particular IL-6, might be a useful tool for the daily clinical management of patients with SAH and CVS.