The "Friday peak" in surgical referrals for spinal metastases: lessons not learned. A retrospective analysis of 201 consecutive cases at a tertiary center.

BACKGROUND: Spinal cord compression and fracture are potential complications of spine metastasis (SM). Rapid management by an expert team can reduce these adverse developments. Delays in seeking therapeutic advices, which lead to the need for sub-optimal emergency procedures, were already demonstrated nearly 20 years ago. We aimed to analyze the current weak points of referrals for vertebral metastasis so as to improve the care pathways. METHODS: We retrospectively reviewed the data of all patients admitted on an emergency or elective basis who underwent palliative surgery for the treatment of neoplastic spine lesions in our institution (tertiary referral neurosurgical unit) between January 2009 and December 2016. RESULTS: This retrospective study included 201 patients, 121 men and 80 women (mean age 65.1 years ± 10.9). Cancer was known for 59.7% of cases. Patients were neurologically asymptomatic in 52.7% of cases (Frankel E), and 123 (60.7%) were hospitalized for emergency reasons, including 51 (41.5% of emergencies) on a Friday (p < 0.0001). A significant increase in emergencies occurred over the studied period (p = 0.0027). The "emergency" group had significantly unfavorable results in terms of neurological status (p < 0.001), the occurrence of complications (p = 0.04), the duration of hospitalization (p = 0.02), and the clinical evolution (p = 0.04). Among 123 patients hospitalized for emergency reasons, 65 (52.8%) had known cancers, of which 33 had an identified SM, including 22 with neurological deficits (Frankel A-D), without prior surgical assessment (17.8% of emergencies). CONCLUSION: Too many patients with previously identified metastases are referred for emergency reasons, including with a neurological deficit. Optimizing upstream pathways and referrals is imperative for improving the management of these patients. Involving a spine surgeon at the slightest symptom or an abnormal image is critical for defining the best treatment upstream. The use of telemedicine and the development of dedicated tumor boards are ways of improving this involvement.

Enhancing the referral process for surgical management of spinal metastases: insights from a 12-year, bi-institutional study of 533 patients.

Introduction: Delayed surgical management of spinal metastases (SMs) can have detrimental effects on patient survival and quality of life, leading to pain and potential neurological impairment. This study aimed to assess the impact of delayed referral for SMs on clinical outcomes by analyzing patients managed in emergency situations. Methods: We retrospectively reviewed the data of all patients admitted on either emergency or elective basis who underwent surgery for the treatment of neoplastic spine lesions at our two institutions (tertiary referral neurosurgical units) between January 2008 and December 2019. Results: We analyzed 210 elective (EGp) and 323 emergency patients (UGp); emergencies increased significantly over the 12-year period, with a Friday peak (39.3%) and frequent neurological impairment (61.6% vs. 20%). Among the UGp patients, 186 (7.5%) had a previously monitored primitive cancer, including 102 (31.6%) with known SMs. On admission, 71 of the 102 (69.9%) patients presented with neurological deficits. UGp patients were more likely to undergo a single decompression without fixation. Outcomes at the 3-month follow-up were significantly worse for UGp patients ([very] poor, 29.2 vs. 13.8%), and the median overall survival for UGp patients was statistically lower. Risk factors for patients with SM undergoing emergency management included short delay between onset of symptoms and first contact with a spine surgeon, and an initial motor deficit. Conclusion: Many patients with previously identified metastases, including those with neurological deficits, are urgently referred. Optimization is needed in the oncology pathway, and all stakeholders must be made aware of the factors contributing to the improvement in the clinical and radiological identification of potential complications affecting patient survival and quality of life.

Oxidative phosphorylation is a metabolic vulnerability of endocrine therapy and palbociclib resistant metastatic breast cancers.

Resistance to endocrine treatments and CDK4/6 inhibitors is considered a near-inevitability in most patients with estrogen receptor positive breast cancers (ER + BC). By genomic and metabolomics analyses of patients' tumours, metastasis-derived patient-derived xenografts (PDX) and isogenic cell lines we demonstrate that a fraction of metastatic ER + BC is highly reliant on oxidative phosphorylation (OXPHOS). Treatment by the OXPHOS inhibitor IACS-010759 strongly inhibits tumour growth in multiple endocrine and palbociclib resistant PDX. Mutations in the PIK3CA/AKT1 genes are significantly associated with response to IACS-010759. At the metabolic level, in vivo response to IACS-010759 is associated with decreased levels of metabolites of the glutathione, glycogen and pentose phosphate pathways in treated tumours. In vitro, endocrine and palbociclib resistant cells show increased OXPHOS dependency and increased ROS levels upon IACS-010759 treatment. Finally, in ER + BC patients, high expression of OXPHOS associated genes predict poor prognosis. In conclusion, these results identify OXPHOS as a promising target for treatment resistant ER + BC patients.

CT-Guided Percutaneous Vertebroplasty of the Cervico-Thoracic Junction for the Management of Pathologic Fracture or Symptomatic Lytic Lesion in Cancer Patients.

OBJECTIVES: The purpose of this retrospective observational study is to report author's experience in computed-tomography (CT)-guided percutaneous vertebroplasty (PV) of the cervicothoracic junction. METHODS: The records of all consecutive patients treated by PV at levels C7, T1, T2, and T3 in a tertiary cancer center during year 2020 were extracted from the Institutional electronic archive. Following data were collected: demographics, indication for PV, procedure features, outcomes, and complications. Technical success was defined as when the trocar was placed into the vertebral body, allowing the injection of polymethyl-metacrylate (PMMA). RESULTS: Eleven patients were identified who received PV on 14 levels. Mean procedure duration was 57 ± 22 min (range [31-142]). A "trans-pedicular approach at the targeted level" was used in 1 vertebra (7%), a "costotransverse approach, at the targeted level" was used in 1 vertebra (7%), a "transpedicular approach via the level below" was used in 3 vertebrae (22%), and a "costotransverse approach via the level below" was used in 9 vertebrae (64%). Meantime to deploy each trocar was 20 ± 5 min (range [12-32]). Technical success was achieved in 14/14 (100%) of vertebrae. Mean postoperative hospitalization duration was 1.9 ± 1.7 days (range [1-11]). According to CIRSE classification, no adverse event occurred. PMMA leakage occurred in two patients; both remained asymptomatic. CONCLUSION: This study provides arguments in favor of safety and efficiency of CT-guided vertebroplasty of levels C7, T1, T2, and T3, for both trocar deployment and monitoring of the vertebral body filling during the PMMA injection.

Addressing the dosimetric impact of bone cement and vertebroplasty in stereotactic body radiation therapy.

PURPOSE: Bone cement used for vertebroplasty can affect the accuracy on the dose calculation of the radiation therapy treatment. In addition the CT values of high density objects themselves can be misrepresented in kVCT images. The aim of our study is then to propose a streamlined approach for estimating the real density of cement implants used in stereotactic body radiation therapy. METHODS: Several samples of cement were manufactured and irradiated in order to investigate the impact of their composition on the radiation dose. The validity of the CT conversion method for a range of photon energies was investigated, for the studied samples and on six patients. Calculations and measurements were carried out with various overridden densities and dose prediction algorithms (AXB with dose-to-medium reporting or AAA) in order to find the effective density override. RESULTS: Relative dose differences of several percent were found between the dose measured and calculated downstream of the implant using an ion chamber and TPS or EPID dosimetry. If the correct density is assigned to the implant, calculations can provide clinically acceptable accuracy (gamma criteria of 3%/2 mm). The use of MV imaging significantly favors the attribution of a correct equivalent density to the implants compared to the use of kVCT images. CONCLUSION: The porosity and relative density of the various studied implants vary significantly. Bone cement density estimations can be characterized using MV imaging or planar in vivo dosimetry, which could help determining whether errors in dose calculations are due to incorrect densities.

In vitro bone metastasis dwelling in a 3D bioengineered niche.

Bone is the most frequent metastasis site for breast cancer. As well as dramatically increasing disease burden, bone metastases are also an indicator of poor prognosis. One of the main challenges in investigating bone metastasis in breast cancer is engineering in vitro models that replicate the features of in vivo bone environments. Such in vitro models ideally enable the biology of the metastatic cells to mimic their in vivo behavior as closely as possible. Here, taking benefit of cutting-edge technologies both in microfabrication and cancer cell biology, we have developed an in vitro breast cancer bone-metastasis model. To do so we first 3D printed a bone scaffold that reproduces the trabecular architecture and that can be conditioned with osteoblast-like cells, a collagen matrix, and mineralized calcium. We thus demonstrated that this device offers an adequate soil to seed primary breast cancer bone metastatic cells. In particular, patient-derived xenografts being considered as a better approach than cell lines to achieve clinically relevant results, we demonstrate the ability of this biomimetic bone niche model to host patient-derived xenografted metastatic breast cancer cells. These patient-derived xenograft cells show a long-term survival in the bone model and maintain their cycling propensity, and exhibit the same modulated drug response as in vivo. This experimental system enables access to the idiosyncratic features of the bone microenvironment and cancer bone metastasis, which has implications for drug testing.

The French mobile neurosurgical unit.

The authors present the French concept of a mobile neurosurgical unit (MNSU) as used to provide specific support to remote military medicosurgical units deployed in Africa, South America, Central Europe, and Afghanistan. From 2001 to 2009, 15 missions were performed, for 16 patients. All but 3 of these missions (those in Kosovo, French Guyana, and Afghanistan) concerned Africa. Eleven patients were French soldiers, 3 were civilians, and 2 were Djiboutian soldiers. The conditions that MNSUs were requested for included craniocerebral wounds (2 cases), closed head trauma (7 cases), spinal trauma (5 cases), and spontaneous intracranial hemorrhage (2 cases). In 5 of the 16 cases, neurosurgical treatment was provided on site. All French soldiers and 2 civilians were evacuated to France. The MNSU can be deployed for timely treatment when some delay in neurosurgical management is acceptable.

PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance.

A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Here we perform whole exome sequencing and gene expression analysis of matched primary breast tumours and bone metastasis-derived patient-derived xenografts (PDX). Transcriptomic analyses reveal enrichment of the G2/M checkpoint and up-regulation of Polo-like kinase 1 (PLK1) in PDX. PLK1 inhibition results in tumour shrinkage in highly proliferating CCND1-driven PDX, including different RB-positive PDX with acquired palbociclib resistance. Mechanistic studies in endocrine resistant cell lines, suggest an ER-independent function of PLK1 in regulating cell proliferation. Finally, in two independent clinical cohorts of ER positive BC, we find a strong association between high expression of PLK1 and a shorter metastases-free survival and poor response to anastrozole. In conclusion, our findings support clinical development of PLK1 inhibitors in patients with advanced CCND1-driven BC, including patients progressing on palbociclib treatment.

Pulmonary cement embolism after percutaneous vertebroplasty: a rare and nonthrombotic cause of pulmonary embolism.

Percutaneous vertebroplasty consists of injection of acrylic cement - polymethylmethacrylate - into a vertebral body to obtain pain relief and increase its mechanical stability. The procedure is indicated for painful hemangiomas and for painful vertebral compression fractures due to osteoporosis or malignancy. Although vertebroplasty is an efficient treatment, it is not free of complications. We present the case of a patient with pulmonary cement embolism after percutaneous vertebroplasty. Because such patients may be completely asymptomatic, but may also present with acute and severe, cardiovascular instability, clinicians and nuclear physicians should be aware that pulmonary embolism of polymethylmethacrylate may occur after percutaneous vertebroplasty.

Evaluation of quantitative criteria for glioma grading with static and dynamic 18F-FDopa PET/CT.

PURPOSE: The aim of this study was to compare various acquisition and processing protocols for noninvasive glioma grading using either static or dynamic (18)F-FDopa PET. METHODS: Dynamic studies were performed in 33 patients. Based on histopathological analysis, 18 patients had a high-grade (HG) tumor and 15 patients had a low-grade (LG) tumor. For static imaging, SUV(mean) and SUV(max) were calculated for different acquisition time ranges after injection. For dynamic imaging, the transport rate constant k1 was calculated according to a compartmental kinetic analysis using an image-derived input function. RESULTS: With the use of a 5-minute static imaging protocol starting at 38 minutes after injection, newly diagnosed HG tumors could be distinguished from LG tumors with a sensitivity of 70% and a specificity of 90% with a threshold of SUV(mean) of 2.5. In recurrent tumors, a sensitivity of 100% and a specificity of 80% for identifying HG tumors were obtained with a threshold set to 1.8. Dynamic imaging only slightly, but nonsignificantly, improved differential diagnosis. CONCLUSIONS: Static and dynamic imaging without blood sampling can discriminate between LG and HG for both newly diagnosed and recurrent gliomas. In dynamic imaging, excellent discrimination was obtained by considering the transport rate constant k1 of tumors. In static imaging, the best discrimination based on SUV was obtained for SUV(mean) calculated from a 5-minute acquisition started at 38 minutes after injection.

[Brain metastasis from breast cancer: who?, when? and special considerations about the role of technology in neurosurgery]. / Les métastases cérébrales des cancers du sein : qui, quand, et comment les opérer ?

Questions about both the place and the role of surgery on brain metastasis from breast cancer are arising more and more frequently in practice due to the increase of brain metastasis in patients suffering from a form of cancer recognized as one of the most recurrent cancers in adults but also one of the most sensitive to general treatments of the systemic disease. With improvements in anaesthesia, in surgical instruments, and in global care, neurosurgery has taken advantage of new techniques such as pre- and even per-operative imagery and also neuronavigation. These techniques enable radical and effective surgical intervention with a high level of safety for the patient, making neurosurgery perfectly competitive with other therapeutic modalities, particularly on functional grounds. As for symptomatic treatments or other anti-metastasis treatments, most situations allow a reflection on the global therapeutic strategy which can be adapted to individual cases depending on the patient's general prognosis. In developing this global therapeutic strategy, surgical treatment is still as relevant as ever.

External beam radiotherapy in the management of spinal metastases: review of current strategies and perspectives for highly conformal irradiation modalities.

Bone metastases are frequent in advanced metastatic solid tumors. These secondary lesions are responsible for significant impairment of quality of life of patients with onset of pain, which is frequently resistant to standard analgesics. The therapeutic challenge for a patient with spinal metastasis is to maintain a quality of life as good as possible, commensurate with its life expectancy. Radiotherapy can provide efficient pain relief, but it should be integrated into a multidisciplinary approach. In the case of epidural spinal cord compression, it should be performed whenever possible after surgery. New highly conformal irradiation modalities have emerged for treatment of spinal metastases with therapeutic perspectives. Stereotactic radiosurgery could be provided for patients with single lesions or oligometastatic disease, a good general condition, absence of cord compression, and a life expectancy greater than 6 months. It is particularly promising for the treatment of classically radioresistant tumors or relapsing disease. Intensity-modulated radiotherapy, including Helical Tomotherapy, is a new perspective for treatment of multiple metastases. However, if these new techniques can provide efficient pain sedation, hindsight is currently low to judge their therapeutic benefit and these techniques are hardly available in most centers. Here, we offer a quick review of current strategies and new modalities of radiotherapy to put into perspective the place of these techniques in therapy of spinal metastases.

[Brain metastases in breast cancer. Epidemiology and natural history. The Institut Curie experience]. / Métastases cérébrales dans les cancers du sein. Épidémiologie et histoire naturelle. Expérience de l'Institut Curie à travers deux études : les patientes HER2- de moins de 65 ans et les patientes de plus de 65 ans.

Breast cancer is the second cause for brain metastases. Their incidence is rising, partly due to the therapeutic improvements which alter the natural history of breast cancer. Predictive factors for brain metastases have been identified: HER2 oncogene overexpression, lack of expression of hormone receptors, young age and triple negative status. Brain metastases prognosis remains poor with a median survival shorter than 1 year, except for solitary lesions treated by surgery or radiosurgery. We have analysed two series of data from Institut Curie (Paris and Saint-Cloud). In women younger than 65 years, with HER2 negative breast carcinoma, median survival was 7.1 months. In women older than 65 years, median survival was 4 months.

Single anterior procedure for stabilization of a three-part fracture of the axis (odontoid dens and hangman fracture): case report.

STUDY DESIGN: A case of a 3-part fracture of the axis combining an odontoid dens and a hangman fracture is reported. OBJECTIVE: To describe a single anterior procedure allowing stabilization with an odontoid screw fixation and a C2-C3 fusion in a case of complex fracture of the axis. SUMMARY OF BACKGROUND DATA: Even if fractures of the axis are common, multiples fractures of the axis are rare and their management is still challenging for surgeons who have to achieve primary stability, early mobilization, preserved cervical range of motion, and favorable outcome. METHODS: A 79-year-old man was referred in our neurosurgical department 3 weeks after a bicycle accident. He had persistent neck pain without radicular pain. Neurologic examination was normal. The initial CT scan showed a rare and complex fracture of the axis consisting of a fracture of the dens and a traumatic spondylolisthesis of C2-C3. RESULTS: The surgical procedure was performed using an anterior cervical approach under fluoroscopic guidance. First, a C2-C3 fusion was performed using an iliac crest graft. Then an anterior odontoid screw was placed under fluoroscopic guidance. Finally, an anterior plating of C2-C3 covering the odontoid screw was achieved. Postoperative course was uneventful and patient was discharged at day 6. CONCLUSION: This single time procedure was able to achieve primary stability of the fractures of the axis and offers the possibility of an early mobilization of the patient with a good outcome. This approach allowed a better preservation of the cervical range of motion compared with a classic posterior fusion.