Percutaneous CT-guided microwave ablation combined with pedicle screw fixation followed by vertebroplasty (MASFVA): initial experience of a minimally invasive treatment of vertebral metastases with extension to the vertebral pedicle

Background: The aim of this study was to retrospectively evaluate the safety and efficacy of a combined CT-guided percutaneous microwave ablation (MWA) and pedicle screw fixation followed by vertebroplasty (MASFVA) for the treatment and stabilization of painful vertebral metastases with vertebral pedicle involvement. (2) Methods: from January 2013 to January 2017 11 patients with 16 vertebral metastatic lesions (7 men and 5 women; mean age, 65 +/- 11 years) with vertebral metastases underwent CT-guided microwave ablation and screw fixation followed by vertebroplasty (MASFVA). Technical success, complication rate, pain evaluation using a visual analogue scale (VAS), Oswestry Disability Index (ODI) and local tumor control were examined. (3) Results: Technical success rate was 100%. No procedure-related major complications occurred. VAS score decreased from 6.8 +/- 0.7 to 0.6 +/- 0.6. ODI score decreased from 3.1 +/- 0.7 to 1.2 +/- 0.4. All patients could walk independently without neurological complication after one week from the procedure. No new bone fractures or local disease recurrence occurred during a median follow-up of 12 months. (4) Conclusions: Our results suggest that MWA and percutaneous pedicle screw fixation followed by vertebroplasty for the treatment of painful vertebral metastases is a safe and effective procedure for painful vertebral metastases with vertebral pedicle involvement, allowing pain relief and local tumor control

Percutaneous Vertebral Reconstruction (PVR) Technique of Pathological Compression Fractures: An Innovative Combined Treatment of Microwave Ablation, Bilateral Expandable Titanium SpineJack Implants Followed by Vertebroplasty

Background: to retrospectively evaluate safety and efficacy of combined microwave ablation (MWA) and bilateral expandable titanium SpineJack (SJ) implants followed by vertebroplasty (VP) for the treatment of painful thoracolumbar pathological vertebral compression fracture. (2) Methods: from July 2017 to October 2022, twenty-eight patients (13 women and 15 men; mean age 68 ± 11 years) with a history of primary neoplasm and thirty-six painful vertebral metastases with vertebral compression fracture underwent combined MWA and bilateral expandable titanium SpineJack implants with vertebroplasty. We analyzed safety through complications rate, and efficacy through vertebral height restoration and pain decrease, evaluated using a visual analogue scale (VAS), and Functional Mobility Scale (FMS), and local tumor control. Contrast-enhanced CT scans were performed at 1, 3, and 6 months and a contrast-enhanced spine MRI at 6 months after the procedure. (3) Results: Technical success rate was 100%. No procedure-related major complications or death occurred. Vertebral height restoration was observed in 22 levels (58%), with a mean anterior height restoration of 2.6 mm ± 0.6 and a mean middle height restoration of 4.4 mm ± 0.6 (p < 0.001). Mean VAS score of pain evaluation on the day before treatment was 6.3 ± 1.5 (range 4–9). At the 6-month evaluation, the median VAS score for pain was 0.4 ± 0.6 (range 0–2) with a mean reduction of 93.65% (6.8 ± 0.7 vs. 0.4 ± 0.6; p < 0.000) compared with baseline evaluation. Contrast-enhanced CT scans were performed at 1, 3, and 6 months and a contrast-enhanced spine MRI was performed at 6 months after the procedure, showing no local recurrence, implant displacement, or new fractures in the treated site. (4) Conclusions: combined microwave ablation and bilateral expandable titanium SpineJack implants with vertebroplasty is a safe and effective procedure for the treatment of pathological compressive vertebral fractures. The vertebral stabilization achieved early and persistent pain relief, increasing patient mobility, improving recovery of walking capacity, and providing local tumor control

Combined microwave ablation and osteosynthesis for long bone metastases

Background and Objectives: The purpose of this study was to evaluate the feasibility, safety and efficacy of microwave ablation (MWA) in combination with open surgery nail positioning for the treatment of fractures or impending fractures of long bone metastases. Material and Methods: Eleven patients (four men, seven women) with painful bone metastases of the humerus, femur or tibia with non-displaced fractures (one case) or impending fractures (10 cases) underwent open MWA in combination with osteosynthesis by locked nail positioning. Pain intensity was measured using a VAS score before and after treatment. CT or MRI were acquired at one month before and 1, 3, 6, 12 and 18 months after treatment. Results: All procedures were successfully completed without major complications. The level of pain was significantly reduced one month after treatment. For the patients with humerus metastases, the complete recovery of arm use took 8 weeks, while for the patients with femoral metastases the complete recovery of walking capacity took 11 weeks. The VAS score ranged from 7 (4–9) before treatment to 1.5 (0–2.5) after treatment. During a mid-term follow-up of 18 months (range 4–29 months), none of the patients showed tumor relapse or new fractures in the treated site. Two patients died due to tumor disease progression. Conclusion: Results of this preliminary study suggest that combined MWA and surgical osteosynthesis with locked nails is a safe and effective treatment for pathological fractures or malignant impending fractures of long bone metastases of the humerus, femur and tibia. Further analyses with larger cohorts are warranted to confirm these findings

Experts’ consensus on the definition and management of high risk multiple myeloma

High risk multiple myeloma (HRMM) at diagnosis is currently recognized according to the Revised International Staging System (R-ISS) which was set up in 2015. Since then, new clinical and biological prognostic factors have been developed, which could implement the definition of High Risk (HR) category. We conducted a survey in order to identify which additional parameters, both clinical and biological, are considered more useful for the clinical practice and to evaluate if the management of Multiple Myeloma (MM) should change on the basis of the risk category. A questionnaire, consisting of 8 statements, was submitted to 6 Italian experts, from the European Myeloma Network (EMN) Research Italy, using the Delphi method. The colleagues were asked to answer each question using a scale between 0 and 100. If a statement did not reach at least 75 out of 100 points from all the participants, it was rephrased on the basis of the proposal of the experts and resubmitted in a second or further round, until a consensus was reached among all. From the first round of the survey a strong consensus was reached regarding the opportunity to revise the R-ISS including chromosome 1 abnormality, TP53 mutation or deletion, circulating plasma cells by next generation flow and extramedullary plasmacytomas. No consensus was reached for the definition of “double hit” MM and for the application in clinical practice of treatment strategies based on the risk category. In the second round of the Delphi questionnaire, “double-hit” MM was recognized by the association of at least two high-risk cytogenetic or molecular abnormalities. Moreover, the experts agreed to reserve an intensified treatment only to specific conditions, such as plasma cell leukaemia or patients with multiple extramedullary plasmacytomas, while they admitted that there are not sufficient real word data in order to modify treatment on the basis of MRD assessment in clinical practice. This survey suggests that the definition of HRMM should be implemented by additional clinical and biological risk factors, that will be useful to guide treatment in the future

Language of CTO interventions – Focus on hardware

AbstractThe knowledge of variety of chronic total occlusion (CTO) hardware and the ability to use them represents the key to success of any CTO interventions. However, the multiplicity of CTO hardware and their physical character and the terminology used by experts create confusion in the mind of an average interventional cardiologist, particularly a beginner in this field. This knowledge is available but is scattered. We aim to classify and compare the currently used devices based on their properties focusing on how physical character of each device can be utilized in a specific situation, thus clarifying and simplifying the technical discourse

Pentraxin 3 (PTX3) inhibits plasma cell/stromal cell cross-talk in the bone marrow of multiple myeloma patients

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that binds with high affinity and selectivity to fibroblast growth factor-2 (FGF2), thus inhibiting its pro-angiogenic activity. Here we investigated the effects of PTX3 on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patient-derived bone marrow (BM) plasma cells (PCs), endothelial cells (ECs), and fibroblasts (FBs), and assessed whether PTX3 can modulate the cross-talk between PCs and those microenvironment cells. PTX3 and FGF2 expression was evaluated by ELISA. Functional studies, including cell viability, wound healing, chemotaxis, and Matrigel(\uae) assays, were performed on MGUS and MM ECs and FBs upon the PTX3 treatment. Through western blot PTX3-induced modulation in FGF2/FGF receptor signalling pathways was evaluated in MGUS and MM ECs and FBs through western blot. Co-cultures between MM ECs/FBs and human PC lines were used to evaluate possible PTX3 indirect effects on MM PCs. Adhesion molecules were studied by flow cytometry. PTX3 provides a direct time- and dose-dependent apoptotic effect on MM ECs and FBs, but not on either MM primary PCs or human PC lines. PTX3 inhibits migration of MM ECs and FBs in a dose-dependent manner, and impacts in vitro and in vivo FGF2-mediated MM angiogenesis. Co-cultures of PCs and ECs/FBs show that PTX3 treatment indirectly impairs PC viability and adhesion. We conclude that PTX3 is an anti-angiogenic factor in MM and behaves as a cytotoxic molecule on MM cells by inhibiting the cross-talk between PCs and ECs/FBs. Copyright \ua9 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Survival Risk Scores for Real-Life Relapsed/Refractory Multiple Myeloma Patients Receiving Elotuzumab or Carfilzomib In Combination With Lenalidomide and Dexamethasone as Salvage Therapy: Analysis of 919 Cases Outside Clinical Trials

The present study aimed to develop two survival risk scores (RS) for overall survival (OS, SRSKRd/EloRd) and progression-free survival (PFS, PRSKRd/EloRd) in 919 relapsed/refractory multiple myeloma (RRMM) patients who received carfilzomib, lenalidomide, and dexamethasone (KRd)/elotuzumab, lenalidomide, and dexamethasone (EloRd). The median OS was 35.4 months, with no significant difference between the KRd arm versus the EloRd arm. In the multivariate analysis, advanced ISS (HR = 1.31; P = 0.025), interval diagnosis–therapy (HR = 1.46; P = 0.001), number of previous lines of therapies (HR = 1.96; P < 0.0001), older age (HR = 1.72; P < 0.0001), and prior lenalidomide exposure (HR = 1.30; P = 0.026) remained independently associated with death. The median PFS was 20.3 months, with no difference between the two strategies. The multivariate model identified a significant progression/death risk increase for ISS III (HR = 1.37; P = 0.002), >3 previous lines of therapies (HR = 1.67; P < 0.0001), older age (HR = 1.64; P < 0.0001), and prior lenalidomide exposure (HR = 1.35; P = 0.003). Three risk SRSKRd/EloRd categories were generated: low-risk (134 cases, 16.5%), intermediate-risk (467 cases, 57.3%), and high-risk categories (213 cases, 26.2%). The 1- and 2-year OS probability rates were 92.3% and 83.8% for the low-risk (HR = 1, reference category), 81.1% and 60.6% (HR = 2.73; P < 0.0001) for the intermediate-risk, and 65.5% and 42.5% (HR = 4.91; P < 0.0001) for the high-risk groups, respectively. Notably, unlike the low-risk group, which did not cross the median timeline, the OS median values were 36.6 and 18.6 months for the intermediate- and high-risk cases, respectively. Similarly, three PRSKRd/EloRd risk categories were engendered. Based on such grouping, 338 (41.5%) cases were allocated in the low-, 248 (30.5%) in the intermediate-, and 228 (28.0%) in the high-risk groups. The 1- and 2-year PFS probability rates were 71.4% and 54.5% for the low-risk (HR = 1, reference category), 68.9% and 43.7% (HR = 1.95; P < 0.0001) for the intermediate-risk, and 48.0% and 27.1% (HR = 3.73; P < 0.0001) for the high-risk groups, respectively. The PFS median values were 29.0, 21.0, and 11.7 months for the low-, intermediate-, and high-risk cases. This analysis showed 2.7- and 4.9-fold increased risk of death for the intermediate- and high-risk cases treated with KRd/EloRd as salvage therapy. The combined progression/death risks of the two categories were increased 1.3- and 2.2-fold compared to the low-risk group. In conclusion, SRSKRd/EloRd and PRSKRd/EloRd may represent accessible and globally applicable models in daily clinical practice and ultimately represent a prognostic tool for RRMM patients who received KRd or EloRd

The next generation of novel therapies for the management of relapsed multiple myeloma

The advent of various novel therapies such as immunomodulators and proteasome inhibitors has transformed the treatment paradigm for patients with multiple myeloma (MM). As a result, the overall survival has improved dramatically over the last decade. Despite these advances, MM remains mostly incurable and most patients experience disease relapse after enjoying a period of disease control or remission. Fortunately, the scientific community continues to make strides in developing 'next-generation' therapies for the management of patients with relapsed MM. This review will summarize the efficacy of some of the newest therapeutic agents available for the treatment of patients with relapsed MM after their upfront treatment with the original novel agents such as thalidomide, lenalidomide and bortezomib