Peptide radionuclide radiation therapy with Lutathera in multirecurrent nonanaplastic meningiomas: antitumoral activity study by growth rate analysis.

PURPOSE: Several retrospective studies and meta-analyses of Peptide Radionuclide Radiation Therapy in meningiomas suggest six-month progression-free survival improvement for WHO grade 1 and 2 meningiomas. In the present study, we aimed to evaluate the impact of such treatment on three-dimensional volume growth rate (3DVGR) in nonanaplastic meningiomas. METHODS: The authors performed a retrospective study including eight patients treated with Lutathera®. Millimetric 3D T1-weighted with gadolinium enhancement magnetic resonance imaging sequences were requested for volume measurement. Then, tumor growth rate was classified following a previously described 3DVGR classification (Graillon et al.). RESULTS: Patients harbored seven WHO grade 2 meningiomas and one aggressive WHO grade 1. All patients, except one, underwent four treatment cycles. 3DVGR significantly decreased at 3, 6, and 12 months after treatment initiation analyzing each lesion separately. Mean and median 3DVGR from all patients were respectively at 29.5% and 44.5%/6 months before treatment initiation, then at 16.5% and 25%/6 months at three months post-treatment initiation, 9.5% and 4.5%/6 months after 6 months, as well as 9.5% and 10.5%/6 months after 12 months. At 3, 6, and 12 months after treatment initiation, 4/8, 6/7, and 5/6 patients were class 2 (stabilization or severe 3DVGR slowdown), respectively. No patient was class 1 at 6 and 12 months, suggesting a lack of drug response. CONCLUSION: In nonanaplastic meningiomas, Lutathera®'s antitumoral activity appeared delayed and more likely observed at six months, while no major response was observed under treatment. Moreover, its antitumoral activity persisted for 12-18 months following treatment initiation.

Primary central nervous system lymphoma (PCNSL) in older patients.

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare, chemo and radio-sensitive tumor limited to the central nervous system. The incidence of PCSNL increases notably in the elderly population which represented approximately half of the patients. The limit of 'elderly' population remained debated and nonuniform, including 60 years as a cutoff for brain radiotherapy, 65 years for autologous stem-cell transplantation, and 70 years for the last clinical trials. Current therapeutic options include first line treatment based on high-dose methotrexate based polychemotherapy, consolidation chemotherapy, and adapted autologous stem cell transplantation for highly selected patients. At relapse, single agent targeted therapies or salvage chemotherapy followed by intensive consolidation are promising therapeutic options. Nevertheless, improving management of elderly patients is an urgent medical need that currently remains unresolved. OBJECTIVE: We will focus on elderly patients with PCNSL and their specificities including clinical presentations, available therapeutic options and adaptations to be made. CONCLUSION: To improve survival, it will be necessary to personalized and adapt the treatments, to each patient and his comorbidities, to increase their effectiveness and limit their toxicity in this frail population. Finally, inclusion of these patients in clinical trials is one of the major challenges to significantly change PCNSL elderly patient prognosis.

Deciphering the Action of Neuraminidase in Glioblastoma Models.

Glioblastoma (GBM) contains cancer stem cells (CSC) that are resistant to treatment. GBM CSC expresses glycolipids recognized by the A2B5 antibody. A2B5, induced by the enzyme ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyl transferase 3 (ST8Sia3), plays a crucial role in the proliferation, migration, clonogenicity and tumorigenesis of GBM CSC. Our aim was to characterize the resulting effects of neuraminidase that removes A2B5 in order to target GBM CSC. To this end, we set up a GBM organotypic slice model; quantified A2B5 expression by flow cytometry in U87-MG, U87-ST8Sia3 and GBM CSC lines, treated or not by neuraminidase; performed RNAseq and DNA methylation profiling; and analyzed the ganglioside expression by liquid chromatography-mass spectrometry in these cell lines, treated or not with neuraminidase. Results demonstrated that neuraminidase decreased A2B5 expression, tumor size and regrowth after surgical removal in the organotypic slice model but did not induce a distinct transcriptomic or epigenetic signature in GBM CSC lines. RNAseq analysis revealed that OLIG2, CHI3L1, TIMP3, TNFAIP2, and TNFAIP6 transcripts were significantly overexpressed in U87-ST8Sia3 compared to U87-MG. RT-qPCR confirmed these results and demonstrated that neuraminidase decreased gene expression in GBM CSC lines. Moreover, neuraminidase drastically reduced ganglioside expression in GBM CSC lines. Neuraminidase, by its pleiotropic action, is an attractive local treatment against GBM.

TP5: A Novel Therapeutic Approach Targeting Aberrant and Hyperactive CDK5/p25 for the Treatment of Colorectal Carcinoma.

Colorectal carcinoma (CRC) is a prevalent cancer worldwide with a high mortality rate. Evidence suggests that increased expression of Cyclin-dependent kinase 5 (CDK5) contributes to cancer progression, making it a promising target for treatment. This study examined the efficacy of selectively inhibiting CDK5 in colorectal carcinoma using TP5, a small peptide that selectively inhibits the aberrant and hyperactive CDK5/p25 complex while preserving physiological CDK5/p35 functions. We analyzed TP5's impact on CDK5 activity, cell survival, apoptosis, the cell cycle, DNA damage, ATM phosphorylation, and reactive oxygen species (ROS) signaling in mitochondria, in CRC cell lines, both alone and in combination with chemotherapy. We also assessed TP5's efficacy on a xenograft mouse model with HCT116 cells. Our results showed that TP5 decreased CDK5 activity, impaired cell viability and colony formation, induced apoptosis, increased DNA damage, and led to the G1 phase arrest of cell cycle progression. In combination with irinotecan, TP5 demonstrated a synergy by leading to the accumulation of DNA damage, increasing the γH2A.X foci number, and inhibiting G2/M arrest induced by Sn38 treatment. TP5 alone or in combination with irinotecan increased mitochondrial ROS levels and inhibited tumor growth, prolonging mouse survival in the CRC xenograft animal model. These results suggest that TP5, either alone or in combination with irinotecan, is a promising therapeutic option for colorectal carcinoma.

Prognostic value of circulating lymphocyte subsets in primary central nervous system lymphoma.

BACKGROUND: Immunity plays an important role in CNS-DLBCL development. CNS-DLBCL predictive factors need to be improved. OBJECTIVE: To evaluate the predictive value of circulating lymphocyte subsets in PCNSL patients. METHODS: We prospectively analyzed blood lymphocyte immunophenotyping (LIP) in newly CNS-DLBCL referred to our institution between December 2013 and January 2020. LIP analysis was performed before rituximab and chemotherapy administration. The clinical, radiological, histological, biological and treatment data were retrospectively collected. RESULTS: Fifty-three patients were included with a median age of 69.7 (range 21.7-87.5). Median KPS was 60 (range 30-100). Thirty-three patients (64%) presented with one or several lymphopenias: 21 (40%), 24 (46%) and 9 (17%) NK, T and B lymphopenias respectively. Only 11 patients (21%) had normal LIP. Median CD4+/CD8+ ratio was 2.11 (range 0.54-9.11). This ratio was normal, low or high in 27%, 28% and 44% of patients respectively. The presence of steroids did not impact LIP results. Complete, partial responses, stable and progressive disease (PD) were observed in 24 (50%), 10 (21%), 4 (8%), and 10 (21%) patients respectively. CD4+/CD8+ ratio tended to be different between refractory (PD patients) and non-refractory patients (p = 0.077, ROC AUC: 0.684). Median progression-free survival (PFS) and overall survival (OS) were 14.7 (95%CI 6.5-22.9) and 43.2 (95%CI 21.6-64.9) months, respectively. In multivariate analyses, adjusted by KPS, a CD4+/CD8+ ratio > 1.97 was associated with poor PFS [p = 0.043, HR = 3.32 (1.02-4.88)] and tended to be associated with worse OS (p = 0.064). CONCLUSION: LIP at baseline may predict refractory disease and exhibits a prognostic value in CNS-DLBCL patients.

Adult H3K27M mutated thalamic glioma patients display a better prognosis than unmutated patients.

BACKGROUND: Adult thalamic gliomas are a rare entity whose management is challenging for physicians. The aim of this study is to describe the characteristics and prognostic factors of thalamic gliomas in adult patients. METHODS: We retrospectively analyzed the clinical, neuro-radiological, histological, and molecular characteristics of all cases of adult thalamic glioma in our regional center. RESULTS: We included 38 adult patients. Median age at diagnosis was 56.5 years old (range, 24-80). Median KPS at diagnosis was 70%. Two-thirds of patients presented with tumor necrosis on MRI. Bithalamic lesions were present in four patients. The median volume of enhancement associated with lesions was relatively small (14 mm3). Two patients had undergone partial surgical resection. All other patients underwent biopsy. Median PFS was 7.1 months (95% CI [3.7-10.5]) and median OS was 15.6 months (95% CI [11.7-19.6]). Among 20 patients with available tumor samples for molecular analyses, only 4 (20%) presented with H3K27M mutation. Patients with H3K27M mutation had longer survival compared to those without. Finally, we identified a long-term survivor population characterized by a younger age, no cognitive impairment, low steroid dose treatment and the presence of H3K27M mutation. CONCLUSION: Thalamic adult glioma differs from bithalamic glioma in children with regards to its clinical, radiological and molecular profiles. Long-term survival is observed in young patients with limited symptoms and H3K27M mutation. A larger prospective cohort is needed to validate these findings.

Chemotherapy and targeted therapies for meningiomas: what is the evidence?

PURPOSE OF REVIEW: Although most meningiomas are slow growing tumors mainly controlled by surgery with or without radiotherapy, aggressive meningiomas that fail these conventional treatments constitute a rare situation, a therapeutic challenge and an unmet need in neuro-oncology. RECENT FINDING: Mutational landscape in recurrent high-grade meningiomas includes mainly NF2 mutation or 22q chromosomal deletion, whereas telomerase reverse transcriptase promoter, BAP-1 and CDK2NA mutations were also found in aggressive meningiomas. Pi3K-Akt-mTOR pathway is currently the most relevant intracellular signaling pathway target in meningiomas with preliminary clinical activity observed. Assessment of drug activity with progression free survival rate at 6 months is challenging in regard to meningioma growth rate heterogeneity, so that 3-dimensional growth rate before and during treatment could be considered in the future to selected new active drugs. SUMMARY: Despite a low evidence level, some systemic therapies may be considered for patients with recurrent meningioma not amenable to further surgery or radiotherapy. In recurrent high-grade meningioma, everolimus-octreotide combination, bevacizumab, sunitinib and peptide receptor radionuclide therapy exhibit a signal of activity that may justify their clinical use. Despite a lack of clear signal of activity to date, immunotherapy may offer new perspectives in the treatment of these refractory tumors.

TEMOBIC: Phase II Trial of Neoadjuvant Chemotherapy for Unresectable Anaplastic Gliomas: An ANOCEF Study.

LESSONS LEARNED: Treatment with temozolomide and BCNU was associated with substantial response and survival rates for patients with unresectable anaplastic glioma, suggesting potential therapeutic alternative for these patients. The optimal treatment for unresectable large anaplastic gliomas remains debated. BACKGROUND: The optimal treatment for unresectable large anaplastic gliomas remains debated. METHODS: Adult patients with histologically proven unresectable anaplastic oligodendroglioma or mixed gliomas (World Health Organization [WHO] 2007) were eligible. Treatment consisted of BCNU (150 mg/m2 ) and temozolomide (110 mg/m2 for 5 days) every 6 weeks for six cycles before radiotherapy. RESULTS: Between December 2005 and December 2009, 55 patients (median age of 53.1 years; range, 20.5-70.2) were included. Forty percent of patients presented with wild-type IDH1 gliomas, and 30% presented with methylated MGMT promoter. Median progression-free survival (PFS), centralized PFS, and overall survival (OS) were 16.6 (95% confidence interval [CI], 12.8-20.3), 15.4 (95% CI, 10.0-20.8), and 25.4 (95% CI, 17.5-33.2) months, respectively. Complete and partial responses under chemotherapy were observed for 28.3% and 17% of patients, respectively. Radiotherapy completion was achieved for 75% of patients. Preservation of functional status and self-care capability (Karnofsky performance status [KPS] ≥70) were preserved until disease progression for 69% of patients. Grade ≥ 3 toxicities were reported for 52% of patients, and three deaths were related to treatment. By multivariate analyses including age and KPS, IDH mutation was associated with better prognostic for both PFS and OS, whereas MGMT promoter methylation was associated with better OS. CONCLUSION: The association of BCNU and temozolomide upfront is active for patients with unresectable anaplastic gliomas, but toxicity limits its use.

Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: An LOC network study.

The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.

(R)-GEMOX chemotherapy for unfit patients with refractory or recurrent primary central nervous system lymphoma: a LOC study.

Recurrent primary central nervous system lymphomas (PCNSL) have a very poor prognosis. For young and fit patients, intensive chemotherapy followed by autologous stem cell transplantation could be proposed at relapse. In the other cases (unfit or elderly patients), therapeutic options are limited with no consensual regimen. The poly-chemotherapy by (R)-GEMOX is associated with anti-tumor activity in systemic lymphomas and a favorable toxicity profile. Our objective was to evaluate the activity and tolerance of (R)-GEMOX in PCNSL patients enrolled in the French nation-wide LOC cohort. We retrospectively analyzed all refractory or recurrent patients included in the LOC network who benefited from (R)-GEMOX (rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatine 100 mg/m2). Administration, tolerance, and efficacy data were analyzed. Thirteen patients, treated in five different institutions, benefited from the (R)-GEMOX regimen from February 2013 to August 2017. At the initiation of (R)-GEMOX, median age was 71.4 years old (range, 49.5-82.5) and median Karnofsky performance status (KPS) was 60 (range, 40-80). Seven patients were in second line of treatment whereas the six others were in third line or over. All patients had received methotrexate-based polychemotherapy as first-line treatment except one. Overall response rate was 38% with two complete responses and three partial responses. Median progression-free survival was 3.2 months (95%CI: 0.2-6.2), and median overall survival was 8.2 months (95%CI: 0.6-15.8). Toxicity was mainly hematological including grade ¾ neutropenia (38%), lymphopenia (23%), and thrombopenia (23%). Older age (p = 0.046) and low KPS (p = 0.054) tended to be associated with a worse prognosis. (R)-GEMOX is associated with substantial response rate and favorable toxicity profile in unfit patients with recurrent PCNSL. (R)-GEMOX could be considered to be an additional option in patients with recurrent/refractory PCNSL.

Neuro-radiological characteristics of adult diffuse grade II and III insular gliomas classified according to WHO 2016.

INTRODUCTION: The phenotypic heterogeneity of diffuse gliomas is still inconsistently explained by known molecular abnormalities. Here, we report the molecular and radiological features of diffuse grade WHO II and III gliomas involving the insula and its potential impact on prognosis. METHODS: Clinical, pathological, molecular and neuro-radiological features of 43 consecutive patients who underwent a surgical resection between 2006 and 2013 for a grade II and III gliomas involving the insula was retrospectively analyzed. RESULTS: Median age was 44.4 years. Eight patients had oligodendrogliomas, IDH mutant (IDHmut) and 1p/19q-codeleted (6 grade II, 2 grade III). Twenty-eight patients had diffuse astrocytomas, IDHmut (22 grade II and 6 grade III) and seven patients had grade II diffuse astrocytomas, IDHwt (A-IDHwt). Vimentin staining was exclusively recorded in tumor cells from A-IDHwt (p = 0.001). Mean cerebral blood volume (CBV) (p = 0.018), maximal value of CBV (p = 0.017) and ratio of the corrected CBV (p = 0.022) were lower for A-IDHwt. Volumetric segmentation of ADC allowed the identification of the tumor cores, which were smaller in A-IDHwt (p < 0.001). The tumor occurrences of A-IDHwt were exclusively located into the temporo-insular region. Median progression-free survival (PFS) and overall survival (OS) were 50.9 months (95% CI: 26.7-75.0) and 80.9 months (60.1-101.6). By multivariate analysis, A-IDHwt (p = 0.009; p = 0.019), 7p gain and 10q loss (p = 0.009; p = 0.016) and vimentin positive staining (p = 0.011; p = 0.029) were associated with poor PFS and OS respectively. CONCLUSIONS: Insular low-grade A-IDHwt presented with poor prognosis despite a smaller tumor core and no evidence of increased perfusion on MR imaging.

Correction to: Neuro-radiological characteristics of adult diffuse grade II and III insular gliomas classified according to WHO 2016.

In the initial, online publication, the authors' given names were captured as family names and vice versa. The names are correctly shown here. The original article has been corrected.

Coping strategies and quality of life: a longitudinal study of high-grade glioma patient-caregiver dyads.

BACKGROUND: Among a sample of patient-informal caregiver dyads in the specific context of new diagnoses of high-grade glioma in the time-frame between diagnosis and the third month following diagnosis, we examine whether the coping strategies implemented by the patients and their caregivers influenced their own quality of life (QoL) and the QoL of their relatives. METHODS: Thirty-eight dyads with patients having recent diagnoses of high-grade glioma were involved in this longitudinal study. The self-reported data include QoL (Patient-Generated Index, EORTC QLQ-C30, and CareGiver Oncology Quality of Life), and coping strategies (BriefCope). Data were collected at T1 corresponding to the time-frame between diagnosis and postsurgical treatment initiation and T2 corresponding to the 3-month post-inclusion follow-up. RESULTS: Coping strategies based on social support and avoidance were the least used at baseline and the 3-month follow-up, both for patients and caregivers. At the 3-month follow-up, the use of social support at baseline was significantly related to lower scores of QoL for the patients and with higher QoL for the caregivers. For the patient, the use of problem-solving or positive thinking at baseline was not related to his/her QoL, while it was related to more satisfactory QoL scores for the caregiver. The use of avoidance at baseline was linked to a higher 3-month QoL for the patients and a lower 3-month QoL for the caregivers. Using the specific dyadic analyses (actor-partner interdependence model), the 3-month patient's QoL was lower (ß = - 0.322; p = 0.03) when the patient mobilized the social support strategy at baseline, but was higher(ß = 0.631; p < 10- 3) when his/her informal caregiver used this strategy. After adjustment for sex, age, and baseline PGI score, the link between high use of the social support strategy at baseline by the caregiver and the patient's 3-month QoL, remained present (positive partner effect; ß =0.675; p < 10- 3). CONCLUSION: The QoL for patients and their informal caregivers since the time of diagnosis is directly related to the use of coping strategies based on social support at time of diagnosis.

Relationship between magnetic resonance imaging characteristics and plasmatic levels of MMP2 and MMP9 in patients with recurrent high-grade gliomas treated by Bevacizumab and Irinotecan.

Matrix metalloproteases MMP2 and MMP9 are involved in cancer angiogenesis and invasion. We recently demonstrated that plasma MMP2 and MMP9 levels could both predict response to bevacizumab in patients with recurrent high-grade glioma (HGG). We examined the potential relationship between MMP2/MMP9 plasma levels and glioma imaging characteristics. In this retrospective, monocentric study, MRI before bevacizumab administration for HGG patients was independently analyzed for contrast enhancement (CE) and FLAIR sequences. Contemporary MMP2 and MMP9 plasma levels were assessed using ELISA kits. We analyzed 28 patients with a median Karnofsky Performance Status of 70 (range 50-80). A diffuse pattern was observed in 14 patients (50%). We did not observe any correlation between baseline imaging features and plasma levels of MMP2 or MMP9. We found no association between baseline MMP levels and diffuse MRI patterns. In univariate analyses, diffuse pattern, multi-focal disease, tumor diameter, surface area, and volume had no impact on outcome, while the number of lobes involved in CE and crossing of the midline by CE were associated with a worse progression-free survival (p = 0.072 and p = 0.012, respectively) and overall survival (p = 0.012 and p < 0.001, respectively). In patients with recurrent high-grade glioma treated with a bevacizumab-based regimen, our exploratory analysis of multiple MRI tumor characteristics at baseline failed to detect a relationship between imaging feature and plasma levels of MMP2 and MMP9. Our results suggests that number of lobes involved in CE and crossing of the midline by CE are associated with outcome although the potential prognostic versus predictive role of these markers warrant further investigation.

Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort.

The new WHO classification of diffuse gliomas has been refined and now includes the 1p/19q codeletion, IDH1/2 mutation, and histone H3-K27M mutation. Our objective was to assess the prognostic value of the updated 2016 WHO classification in the French POLA cohort. All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nationwide POLA cohort were reclassified according to the updated 4th WHO classification. In total, 1041 patients were included, with a median age at diagnosis of 50.4 years (range 17.1-84.4). Based on the new histomolecular classification, diagnoses included anaplastic oligodendroglioma IDH mutant and 1p/19q-codeleted (32.5 %), anaplastic astrocytoma IDH mutant (IDH (mut)) (11.0 %), anaplastic astrocytoma IDH wild type (IDH (wt)) (5.3 %), glioblastoma IDH (mut) (17.1 %), and glioblastoma IDH (wt) (33.2 %). Ten patients presented with a diffuse midline tumor, H3 K27M mutant. The new WHO classification was prognostic for progression-free survival (PFS) and overall survival (OS) (p < 0.001). We did not find prognosis differences between grades III and IV for IDH (mut) 1p/19q intact and IDH (wt) gliomas in univariate and multivariate analyses. Among anaplastic astrocytoma IDH (wt), cases with chromosome arm 7p gain and 10q loss (55 %) had shorter PFS than the others (p = 0.027). In conclusion, the new WHO histomolecular classification of diffuse gliomas presented with high prognostic value. Grading was not discriminant between grade III and IV high-grade gliomas.

Changes in PlGF and MET-HGF expressions in paired initial and recurrent glioblastoma.

Angiogenesis is one of the key features of glioblastoma (GB). However, the use of anti-angiogenic therapies directed against vascular endothelial growth factor (VEGF) is limited by primary or acquired resistance. MET/HGF and PlGF signaling are involved in potential alternative escape mechanisms to VEGF pathway. Our objective was to explore the potential changes of MET/HGF and PlGF expression, comparing initial diagnosis and recurrence after radiotherapy-temozolomide (RT/TMZ). Paired frozen tumors from both initial and recurrent surgery after radio-chemotherapy were available for 28 patients. RNA expressions of PlGF, MET, and HGF genes were analyzed by RT-qPCR. PlGF expression significantly decreased at recurrence (p = 0.021), and expression of MET showed a significant increase (p = 0.011) at recurrence. RNA expressions of MET and HGF significantly correlated both at baseline and recurrence (baseline: p = 0.005; recurrence: p = 0.019). Evolutive profile (increasing versus decreasing expression at recurrence) of MET was associated with PFS (p = 0.002) and OS (p = 0.022) at recurrence, while the evolutive profile of HGF was associated with PFS at relapse (p = 0.049). Recurrence of GB after chemo-radiation could be associated with a variation in PlGF and MET expression. These results contribute to suggest a modification of the GB angiogenic process between initial diagnosis and recurrence.

Which one is a valuable surrogate for predicting survival between Tomita and Tokuhashi scores in patients with spinal metastases? A meta-analysis for diagnostic test accuracy and individual participant data analysis.

This study is to estimate the diagnostic accuracy of Tokuhashi and Tomita scores that assures 6-month predicting survival regarded as a standard of surgical treatment. We searched PubMed, EMBASE, European PubMed central, and the Cochrane library for papers about the sensitivities and specificities of the Tokuhashi and/or Tomita scores to estimate predicting survival. Studies with cut-off values of ≥9 for Tokuhashi and ≤7 for Tomita scores based on prior studies were enrolled. Sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC), and the best cut-off value were calculated via meta-analysis and individual participant data analysis. Finally, 22 studies were enrolled in the meta-analysis, and 1095 patients from 8 studies were included in the individual data analysis. In the meta-analysis, the pooled sensitivity/specificity/DOR for 6-month survival were 57.7 %/76.6 %/4.70 for the Tokuhashi score and 81.8 %/47.8 %/4.93 for Tomita score. The AUC of summary receiver operating characteristic plots was 0.748 for the Tokuhashi score and 0.714 for the Tomita score. Although Tokuhashi score was more accurate than Tomita score slightly, both showed low accuracy to predict 6 months residual survival. Moreover, the best cut-off values of Tokuhashi and Tomita scores were 8 and 6, not 9 and 7, for predicting 6-month survival, respectively. Estimation of 6-month predicting survival to decide surgery in patients with spinal metastasis is quite limited by using Tokuhashi and Tomita scores alone. Tokuhashi and Tomita scores could be incorporated as part of a multidisciplinary approach or perhaps interpreted in the context of a multidisciplinary approach.

Long-term survivors after surgical management of metastatic spinal cord compression.

PURPOSE: Metastatic spinal cord compression (MSCC) incidences are increasing. Our objective was to identify predictive factors involved in long-term survival after use of a surgical approach. METHODS: We retrospectively analyzed all patients referred to our institution for MSCC who underwent surgery (N = 138). We identified patients with an overall survival (OS) rate greater than 2 years, compared their characteristics to the remaining patients, and performed recursive partitioning analysis (RPA). RESULTS: Median OS was 7.8 months (95 % confidence interval 4.4-11.2). Thirty-nine patients presented with OS ≥2 years. A comparative analysis found significant differences concerning the delay (first symptom-surgery, p < 0.001), number of systemic (p = 0.001) or bone metastases (p = 0.013), Karnofsky performance status (KPS) (p = 0.006), Frankel (p = 0.025), ASA scores (p < 0.001), weight loss (p = 0.003), hyperalgia (p = 0.002), chemotherapy use (p = 0.034), and primary tumor (p < 0.001). RPA classification identified six prognostic classes based on the ASA score, primary type, KPS, and systemic metastases. CONCLUSION: Long-term metastatic cancer survivor patients are an increasing population with specific characteristics.

GD3 ganglioside is a promising therapeutic target for glioma patients.

Glioblastoma is the most frequent and aggressive primary brain tumor in adults. Currently, no curative treatment is available. Despite first-line treatment composed by the association of surgery, radiotherapy, and chemotherapy, relapse remains inevitable in a median delay of 6 to 10 months. Improving patient management and developing new therapeutic strategies are therefore a critical medical need in neuro-oncology. Gangliosides are sialic acid-containing glycosphingolipids, the most abundant in the nervous system, representing attractive therapeutic targets. The ganglioside GD3 is highly expressed in neuroectoderm-derived tumors such as melanoma and neuroblastoma, but also in gliomas. Moreover, interesting results, including our own, have reported the involvement of GD3 in the stemness of glioblastoma cells. In this review, we will first describe the characteristics of the ganglioside GD3 and its enzyme, the GD3 synthase (GD3S), including their biosynthesis and metabolism. Then, we will detail their expression and role in gliomas. Finally, we will summarize the current knowledge regarding the therapeutic development opportunities against GD3 and GD3S.

Early Urinary Potassium Level Predicts High-dose Methotrexate Elimination Delay in Primary Central Nervous System Lymphoma.

BACKGROUND/AIM: Treatment of primary central nervous system lymphoma (PCNSL) includes high dose methotrexate-based polychemotherapy (HD-MTX). This study aimed to identify early predictive factors of methotrexate (MTX) delayed elimination. PATIENTS AND METHODS: We prospectively included all patients with newly-diagnosed PCNSL. Daily serum and urinary creatinine and ionogram were collected. We generated two independent cohorts: a training cohort (TC) and a confirmatory cohort (CC). RESULTS: We included for analysis 64 cures of HD-MTX (20 patients) in the TC and 59 cures (22 patients) in the CC. Median elimination time of MTX was 95 h and 96 h in the TC and CC, respectively. In multivariate analysis, older age (p=0.004), low Karnofsky Performance Status (p=0.036) and high urinary K+ (p=0.001) were associated with delayed MTX elimination. An optimal cutoff for urinary K+ was defined. In the CC, we confirmed that high urinary K+ (p=0.004) remained associated with delayed MTX elimination. CONCLUSION: High urinary K+ may be predictive of delayed MTX elimination in primary central nervous system lymphoma. Its relevance as a decision-making factor needs to be validated in additional prospective studies.