FOLFIRI in advanced platinum-resistant/refractory small-cell lung cancer: a retrospective study.

BACKGROUND: Small-cell lung cancer (SCLC) accounts for approximately 15% of lung cancer and is associated with poor prognosis. In platinum-refractory or -resistant SCLC patients, few treatment options are available. Topotecan is one of the standards of care for these patients, however, due to its high toxicity, several different approaches are employed. FOLFIRI (folinate, 5-fluorouracil and irinotecan) is a chemotherapy regimen used in digestive neuroendocrine carcinoma, which shares pathological similarities with SCLC. In this retrospective study, we evaluated the efficacy and safety of FOLFIRI in patients with platinum-resistant/refractory SCLC. METHODS: Medical records from all consecutive SCLC patients treated with FOLFIRI in a French University Hospital from 2013 to 2021 were analyzed retrospectively. The primary endpoint was the objective response rate according to RECIST v1.1 or EORTC criteria (ORR); secondary endpoints included duration of response, disease control rate, progression-free survival (PFS), overall survival (OS) and safety profile. RESULTS: Thirty-four patients with metastatic platinum-resistant (n = 14) or -refractory (n = 20) SCLC were included. Twenty-eight were evaluable for response, with a partial response observed in 5 patients for an overall ORR in the evaluable population of 17.9% (5/28) and 14.7% (5/34) in the overall population. The disease control rate was 50% (14/28) in the evaluable population. The median PFS and OS were 2.8 months (95%CI, 2.0-5.2 months) and 5.3 months (95%CI, 3.5-8.9 months), respectively. All patients were included in the safety analysis. Grade 3 or 4 adverse events occurred in 13 (38.2%) patients. The most common grade 3 or 4 adverse events were asthenia, neutropenia, thrombopenia and diarrhea. There was no adverse event leading to discontinuation or death. CONCLUSION: FOLFIRI showed some activity for platinum-resistant/refractory SCLC in terms of overall response and had an acceptable safety profile. However, caution is needed in interpreting this result. FOLFIRI could represent a potential new treatment for platinum-resistant/refractory SCLC patients. Further prospective studies are needed to assess the benefits of this chemotherapy regimen.HIGHLIGHTSFOLFIRI showed some activity for platinum-resistant/refractory SCLC in terms of overall response.FOLFIRI was well-tolerated in platinum resistant/refractory SLCL patients.FOLFIRI could represent a potential new treatment for SCLC, prospective studies are needed.

Initial experience, feasibility, and technical development with an electromagnetic navigation assistance in percutaneous pelvic bone cementoplasty: retrospective analysis.

OBJECTIVES: To assess the feasibility and technical outcomes of pelvic bone cementoplasty using an electromagnetic navigation system (EMNS) in standard practice. MATERIALS AND METHODS: Monocentric retrospective study of all consecutive patients treated with cementoplasty or reinforced cementoplasty of the pelvic bone with EMNS-assisted procedures. The endpoints were periprocedural adverse events, needle repositioning rates, procedure duration, and radiation exposure. RESULTS: A detailed description of the technical steps is provided. Thirty-three patients (68 years ± 10) were treated between February 2016 and February 2020. Needle repositioning was required for 1/33 patients (3%). The main minor technical adverse event was soft tissue PMMA cement leaks. No major adverse event was noted. The median number of CT acquisitions throughout the procedures was 4 (range: 2 to 8). Radiation exposure and mean procedure duration are provided. CONCLUSION: Electromagnetic navigation system-assisted percutaneous interventions for the pelvic bone are feasible and lead to low rates of minor technical adverse events and needle repositioning. Procedure duration and radiation exposure were low. KEY POINTS: • Initial experience for 33 patients treated with an electromagnetic navigation assistance for pelvic cementoplasty shows feasibility and safety. • The use of an electromagnetic navigation system does not expose to high procedure duration or radiation exposure. • The system is efficient in assisting the radiologist for extra-axial planes in challenging approaches.

Extraction of cement leakages and malpositioned spindles complicating percutaneous interventions: why, when and how?

OBJECTIVES: Cement leakages in soft tissues are a common occurrence during cementoplasty. They may cause chronic pain, and thus treatment failure. Spindle malposition during reinforced cementoplasty may cause vascular, nerve or cartilage injury. Our goal was to evaluate the rate of cement leakage/spindle extraction and describe the techniques used. METHODS: This retrospective monocentre study included 104 patients who underwent reinforced cementoplasty and 3425 patients who underwent cementoplasty between 2012 and 2020. Operative reports and fluoroscopic images were reviewed to identify extraction attempts and their outcomes. RESULTS: Six patients (5.8%) had a malpositioned spindle, and all of them underwent spindle extraction during reinforced cementoplasty, with an 80% success rate. A total of 7 attempts were performed, using 2 different techniques. One thousand one hundred thirty patients (32%) had a cement leak in soft tissues, and 7 (0.6%) underwent cement leakage extraction during cementoplasty, with a 100% success rate. A total of 10 attempts were performed, using 3 different techniques. No major complication related to the extraction procedures occurred. CONCLUSIONS: Spindle malpositions and soft tissue cement leakages are not uncommon. We described 5 different percutaneous techniques that were safe and effective to extract spindles and paravertebral cement fragments. KEY POINTS: • Soft tissue cement leakages or spindle malpositions are a non-rare occurrence during cementoplasty, and may cause technical failure and/or chronic pain. • Most soft tissue cement fragments and malpositioned spindles can easily be extracted using simple percutaneous techniques.

Reinforced cementoplasty for pelvic tumour lesions and pelvic traumatic fractures: preliminary experience.

OBJECTIVES: Pelvic bone pathological lesions and traumatic fractures are a considerable source of pain and disability. In this study, we sought to evaluate the effectiveness of reinforced cementoplasty (RC) in painful and unstable lesions involving the pelvic bone in terms of pain relief and functional recovery. METHODS: All patients with neoplastic lesion or pelvic fracture for whom a pelvic bone RC was carried out between November 2013 and October 2017 were included in our study. All patients who failed the medical management, patients unsuitable for surgery, and patients with unstable osteolytic lesions were eligible to RC. Clinical outcome was evaluated with a 1-month and 6-month post-procedure follow-up. The primary endpoint was local pain relief measured by the visual analogue scale (VAS). RESULTS: Twenty-two patients (18 females, 4 males; mean age of 65.4 ± 13.3 years [range 38-80]) presenting with painful and unstable pelvic lesions were treated by RC during the study period. Among the 22 patients, 8 patients presented with unstable pelvic fractures (3 patients with iliac crest fracture, 3 with sacral fractures, and the remaining 2 with peri-acetabular fractures). No procedure-related complications were recorded. All patients had significant pain relief and functional improvement at 1 month. One patient (4.5%) had suffered a secondary fracture due to local tumour progression. CONCLUSIONS: Reinforced cementoplasty is an original minimally invasive technique that may help in providing pain relief and effective bone stability for neoplastic and traumatic lesions involving the pelvic bone. KEY POINTS: • Reinforced cementoplasty is feasible in both traumatic fractures and tumoural bone lesions of the pelvis. • Reinforced cementoplasty for pelvic bone lesions provides pain relief and functional recovery. • Recurrence of pelvic bone fracture was observed in 4.5% of the cases in our series.

Reliability and accuracy of time-resolved contrast-enhanced magnetic resonance angiography in hypervascular spinal metastases prior embolization.

OBJECTIVES: Preoperative embolization of hypervascular spinal metastases (HSM) is efficient to reduce perioperative bleeding. However, intra-arterial digital subtraction angiography (IA-DSA) must confirm the hypervascular nature and rule out spinal cord arterial feeders. This study aimed to evaluate the reliability and accuracy of time-resolved contrast-enhanced magnetic resonance angiography (TR-CE-MRA) in assessing HSM prior to embolization. METHODS: All consecutive patients referred for preoperative embolization of an HSM were prospectively included. TR-CE-MRA sequences and selective IA-DSA were performed prior to embolization. Two readers independently reviewed imaging data to grade tumor vascularity (using a 3-grade and a dichotomized "yes vs no" scale) and identify the arterial supply of the spinal cord. Interobserver and intermodality agreements were estimated using kappa statistics. RESULTS: Thirty patients included between 2016 and 2019 were assessed for 55 levels. Interobserver agreement was moderate (κ = 0.52; 95% CI [0.09-0.81]) for TR-CE-MRA. Intermodality agreement between TR-CE-MRA and IA-DSA was good (κ = 0.74; 95% CI [0.37-1.00]). TR-CE-MRA had a sensitivity of 97.9%, a specificity of 71.4%, a positive predictive value of 95.9%, a negative predictive value of 83.3%, and an overall accuracy of 94.6%, for differentiating hypervascular from non-hypervascular SM. The arterial supply of the spine was assessable in 2/30 (6.7%) cases with no interobserver agreement (κ < 0). CONCLUSIONS: TR-CE-MRA can reliably differentiate hypervascular from non-hypervascular SM and thereby avoid futile IA-DSAs. However, TR-CE-MRA was not able to evaluate the vascular supply of the spinal cord at the target levels, thus limiting its scope as a pretherapeutic assessment tool. KEY POINTS: • TR-CE-MRA aids in distinguishing hypervascular from non-hypervascular spinal metastases. • TR-CE-MRA could avoid one-quarter of patients referred for HSM embolization to undergo futile conventional angiography. • TR-CE-MRA's spatial resolution is insufficient to replace IA-DSA in the pretherapeutic assessment of the spinal cord vascular anatomy.

Adapting palliative radiation therapy for bone metastases during the Covid-19 pandemic: GEMO position paper.

The current health crisis caused by COVID-19 is a challenge for oncology treatment, especially when it comes to radiotherapy. Cancer patients are already known to be very fragile and COVID-19 brings about the risk of severe respiratory complications. In order to treat patients safely while protecting medical teams, the entire health care system must optimize the way it approaches prevention and treatment at a time when social distancing is key to stemming this pandemic. All indications and treatment modalities must be re-discussed. This is particularly the case for radiotherapy of bone metastases for which it is possible to reduce the number of sessions, the frequency of transport and the complexity of treatments. These changes will have to be discussed according to the organization of each radiotherapy department and the health situation, while medical teams must remain vigilant about the risks of complications of bone metastases, particularly spinal metastases. In this short piece, the members of the GEMO (the European Study Group of Bone Metastases) offer a number of recommendations to achieve the above objectives, both in general and in relation to five of the most common situations on radiation therapy for bone metastases.

Criteria for inclusion in programs of functional restoration for chronic low back pain: Pragmatic Study.

BACKGROUND: Individuals with chronic low back pain (cLBP) may benefit from multimodal functional restoration programs (FRPs). OBJECTIVE: The aim of this study was to analyze characteristics of individuals with cLBP who were referred or not to an FRP. Because cLBP is a bio-psycho-social disorder, medical and social parameters were analysed. METHODS: This was an observational cross-sectional study performed in 2017 in 6 tertiary centres in France. Consecutive individuals with cLBP visiting a rheumatologist or physical medicine and rehabilitation physician were included. Individuals referred or not to an FRP were compared by demographic characteristics, duration of sick leave over the past year, self-reported physical activity>1h/week, pain (numeric rating scale 0-10), anxiety/depression (Hospital Anxiety and Depression Scale), disability (Oswestry Disability Index) and kinesiophobia (Tampa Kinesiophobia Scale). Univariate and multivariate logistic regression analyses were performed, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 147 individuals with cLBP. The mean (SD) age was 49 (12) years and 88 (60%) were women; 58 (38%) were referred to an FRP. On multivariate analysis, referral to an FRP was associated with reduced pain level (OR: 0.95, 95% CI: 0.91-0.99, for each 1-point increase in pain score), self-reported lack of physical activity (OR: 0.84, 95% CI: 0.72-0.98) and longer sick leave (OR: 1.03, 95% CI: 1.01-1.05, for 30 more days of sick leave). CONCLUSION: In this multicentric observational study, referral to an FRP was linked to pain, self-reported physical activity and sick leave but not medical characteristics assessed. These findings confirm the bio-psycho-social approach of FRPs for cLBP.

Intracardiac cement embolism during percutaneous vertebroplasty: incidence, risk factors and clinical management.

OBJECTIVE: To evaluate the incidence and risk factors for ICE during a PV. MATERIALS AND METHODS: Single-center retrospective analysis of 1512 consecutive patients who underwent 1854 PV procedures for osteoporotic (34 %), malignant (39.9 %) or other cause (26.1 %) of vertebral compression fractures (VCFs)/spine tumor lesions. Only thoracic or lumbar PVs were included. PVs were performed with polymethylmethacrylate (PMMA) low-viscosity bone cement under fluoroscopic guidance. Chest imaging (X-ray or CT) was performed the same day after PV in patients with high clinical suspicion of ICE. All post-procedural chest-imaging examinations were reviewed, and all ICEs were agreed upon in consensus by two radiologists. RESULTS: ICEs were detected in 72 patients (92 cement embolisms). In 86.1 % of the cases, concomitant pulmonary artery cement leakage was detected. Symptomatic ICEs were observed in six cases (8.3% of all ICEs; 0.32% of all PV procedures). No ICE led to death or permanent sequelae. Multiple levels treated during the same PV session were associated with a higher ICE rate [OR: 3.59, 95% CI: (1.98-6.51); p < 0.001]; the use of flat panel technology with a lower ICE occurrence [OR: 0.51, 95% CI: (0.32-0.83); p = 0.007]. CONCLUSION: Intracardiac cement embolism after PV has a low incidence (3.9 % in our study). Symptomatic complications related to ICE are rare (0.3%); none was responsible for clinical sequelae in our series. KEY POINTS: • The incidence of intracardiac cement embolism (ICE) during PVP is low (3.9%). • Having a high number of treated vertebrae during the same session is a significant risk factor for ICE. • Symptomatic intracardiac cement embolisms have a low incidence (8.3% of patients with ICE).

Calpain-6 controls the fate of sarcoma stem cells by promoting autophagy and preventing senescence.

Sarcomas are still unsolved therapeutic challenges. Cancer stem cells are believed to contribute to sarcoma development, but lack of specific markers prevents their characterization and targeting. Here, we show that calpain-6 expression is associated with cancer stem cell features. In mouse models of bone sarcoma, calpain-6-expressing cells have unique tumor-initiating and metastatic capacities. Calpain-6 levels are especially high in tumors that have been successfully propagated in mouse to establish patient-derived xenografts. We found that calpain-6 levels are increased by hypoxia in vitro and calpain-6 is detected within hypoxic areas in tumors. Furthermore, calpain-6 expression depends on the stem cell transcription network that involves Oct4, Nanog, and Sox2 and is activated by hypoxia. Calpain-6 knockdown blocks tumor development in mouse and induces depletion of the cancer stem cell population. Data from transcriptomic analyses reveal that calpain-6 expression in sarcomas inversely correlates with senescence markers. Calpain-6 knockdown suppresses hypoxia-dependent prevention of senescence entry and also promotion of autophagic flux. Together, our results demonstrate that calpain-6 identifies sarcoma cells with stem-like properties and is a mediator of hypoxia to prevent senescence, promote autophagy, and maintain the tumor-initiating cell population. These findings open what we believe is a novel therapeutic avenue for targeting sarcoma stem cells.

Vertebral augmentation with the SpineJack® in chronic vertebral compression fractures with major kyphosis.

OBJECTIVES: Osteoporotic vertebral compression fractures (OVCFs) are an important health issue for which minimally invasive techniques are a feasible treatment. The SpineJack® (Vexim) is an intravertebral expandable system designed to improve the correction of the structural modifications caused by OVCFs. Its ability to stabilise and reduce OVCFs at the acute phase being already well established, we sought to evaluate the feasibility of vertebral augmentation with the SpineJack® in chronic kyphotic OVCFs. METHODS: All consecutive patients treated with the SpineJack® were prospectively included if they met the following criteria: (1) OVCF considered unstable (grade A3 according to Magerl's classification). (2) Local kyphotic angle ≥ 20°. (3) OVCF older than 6 weeks. (4) Back pain with visual analogue scale (VAS) ≥ 4. RESULTS: Nineteen consecutive patients (16 women [84.2%] and 3 men [15.8%]; mean age 73.2 ± 8.2 years) were included. Treatment was performed after a mean delay of 5.8 months ± 2.9 (range 1.5-12). Median visual analogue scale significantly improved from 7 preoperatively (IQR 6-9) to 2 (IQR 1-5) at 6 months (p < 0.01). Significant kyphosis reduction (i.e. ≥ 30%) was obtained in 94.7% of cases. Secondary adjacent level fractures (SALFs) were noted in 21.1% of cases and were correlated with the importance of the kyphosis reduction. CONCLUSIONS: Vertebral augmentation with the SpineJack® is feasible and seems able to correct major structural deformities in chronic OVCFs. SALFs were noted in a substantial amount of cases. Preventive adjacent vertebroplasty might be useful in patients with several risk factors for SALFs. KEY POINTS: • Vertebral augmentation with SpineJack® is effective to correct major structural deformities e.g. height loss and kyphosis. • Successful reduction is reachable with SpineJack® in chronic (older than 6 weeks) OVCFs. • Aggressive reduction of major kyphosis might promote SALFs and complementary adjacent vertebroplasties prevent their occurrence.

Late Nailfold Videocapillaroscopy Pattern Associated With Hand Calcinosis and Acro-Osteolysis in Systemic Sclerosis.

OBJECTIVE: To determine whether calcinosis and acro-osteolysis are related to specific nailfold videocapillaroscopy (NVC) features in patients with systemic sclerosis (SSc; scleroderma). METHODS: NVC and bilateral hand radiographs were systematically performed in 155 consecutively recruited patients with SSc during a 24-month period. Radiologic assessment of calcinosis and acro-osteolysis was performed blinded for the results on NVC features. RESULTS: Patients with calcinosis (n = 29) or acro-osteolysis (n = 25) on radiographs were more likely to have the late pattern on NVC, defined by severe loss of capillaries and neoangiogenesis (P = 0.003 and P < 0.001, respectively). A reduced number of capillaries was significantly found in patients with calcinosis (mean ± SD 3.55 ± 1.76 versus 5.53 ± 2.32 capillaries per finger; P < 0.001) and acro-osteolysis (mean ± SD 2.88 ± 1.30 versus 5.60 ± 2.26 capillaries per finger; P < 0.001). In addition, neoangiogenesis was more frequently observed in patients with severe acro-osteolysis (P = 0.021). Multivariate logistic regression analysis confirmed the independent association between the late NVC pattern and calcinosis (odds ratio [OR] 3.04, 95% confidence interval [95% CI] 1.20-7.68) or acro-osteolysis (OR 4.57, 95% CI 1.66-12.55), together with history of and/or active digital ulcers. CONCLUSION: Acro-osteolysis and calcinosis are independently associated with the late NVC pattern and particularly with severe capillary loss. These results strengthen the link between these radiographic lesions and digital destructive vasculopathy. Moreover, severe acro-osteolysis was more likely to occur with neoangiogenesis, which may suggest an attempt to compensate bone resorption. Further studies are now needed to better understand the physiopathology of calcinosis and acro-osteolysis and determine whether any agent may modify the course of these lesions by influencing vessel damages.