Neuro-Oncology




Specialist Neuro-Oncology Associations (8 links)
Asian Society for Neuro-Oncology
ASNO began annual meetings for neuro-oncology in 2002.
British Neuro Oncology Society
Established in 1980 to promote research and education in Neuro-Oncology and to improve treatment of patients with tumours of the central nervous system.
Cooperative Trials Group for Neuro-Oncology
COGNO was established in 2007, to improve outcomes for patients and those affected by brain tumours through clinical trials research.
European Association for NeuroOncology
EANO
EANO is an organisation for Neurooncologists in Europe formed in 1994. This site includes a background to the organisation, membership details, reports from scientific meetings, clinical trial details, a calendar of events, and links to related sites.
A multidisciplinary, non-profit organization dedicated to promoting advances in neuro-oncology through research and education. Established 1994.
Society of Austrian Neurooncology
SANO
An interdisciplinary non-profit membership association, founded in 2011, which aims to facilitate patient service, research and education in the field of Neurooncology.
日本脳腫瘍学会 | Japan Society for Neuro-Oncology - 日本語 - English
JSNO is a society promoting professional development and international co-operation to advance neuro-oncology, established 1980.
香港神經腫瘤學會 | Hong Kong Neuro-Oncology Society - 中文 - Translate to English
Established in 2011 by neurosurgeons, radiologists, oncologists and pathologists working in the public and private sectors to improve the care and well-being of patients suffering from tumours of the nervous system in Hong Kong.
Recent Research Publications
Italian Cohort of the Nivolumab EAP in Squamous NSCLC: Efficacy and Safety in Patients With CNS Metastases.
Anticancer Res. 2019; 39(8):4265-4271 [PubMed] Related Publications
PATIENTS AND METHODS: Patients in the Italian cohort of the Expanded Access Program (EAP) who had CNS metastases at baseline were analyzed.
RESULTS: Thirty-seven patients with CNS metastases received a median of six doses of nivolumab. Three patients (8%) had grade 3-4 adverse events and one patient discontinued due to an adverse event. The objective response rate was 19%. Median overall survival was 5.8 (95% confidence interval=1.9-9.8) months and median progression-free survival was 4.9 (95% confidence interval=2.7-7.1) months.
CONCLUSION: The safety and efficacy of nivolumab in patients with CNS metastases appear to be similar to those seen in the overall EAP cohort in Italy.
Immune Phenotype Correlates With Survival in Patients With GBM Treated With Standard Temozolomide-based Therapy and Immunotherapy.
Anticancer Res. 2019; 39(4):2043-2051 [PubMed] Related Publications
MATERIALS AND METHODS: Data from 101 patients drawn from the HGG-2010 trial, including baseline patient characteristics and fluorescence-activated cell sorting of immune cell subpopulations, were analyzed by statistical and machine-learning methods.
RESULTS: The analysis revealed strong correlations between immune profiles and overall survival, when the extent of resection and the vaccination schedule were used as stratification variables.
CONCLUSION: A systematic, in silico workflow detecting strong and statistically significant correlations between overall survival and immune profile-derived quantities obtained at the start of dendritic cell vaccination was devised. The derived correlations could serve as a basis for the identification of prognostic markers discriminating between potential long- and short-term survivors of patients with glioblastoma multiforme.
Clinical predictors of radiation-induced lymphopenia in patients receiving chemoradiation for glioblastoma: clinical usefulness of intensity-modulated radiotherapy in the immuno-oncology era.
Radiat Oncol. 2019; 14(1):51 [PubMed] Free Access to Full Article Related Publications
METHODS: We identified patients with glioblastoma treated with RT plus temozolomide from 2006 to 2017. ASL was defined as a TLC of < 500/μL within 3 months after initiating RT. Independent predictors of ASL were determined using logistic regression.
RESULTS: A total of 336 patients were evaluated. Three-dimensional conformal RT (3D-CRT) and intensity-modulated RT (IMRT) were used in 186 (55.4%) and 150 patients (44.6%), respectively. TLC decreased during RT and remained persistently low during the 1-year follow-up, whereas the levels of other blood cell types recovered. In total, 118 patients (35.1%) developed ASL. During a median follow-up of 19.3 months, patients with ASL showed significantly worse overall survival than did those without ASL (median, 18.2 vs. 22.0 months; P = .028). Multivariable analysis revealed that increased planning target volume (PTV) was independently associated with increased ASL incidence (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00-1.03; P = .042), while IMRT was independently associated with decreased ASL incidence (HR, 0.48; 95% CI, 0.27-0.87; P = .015). A propensity-matched comparison showed that the incidence of ASL was lower with IMRT than with 3D-CRT (20% vs. 37%; P = .005).
CONCLUSIONS: IMRT and low PTV were significantly associated with decreased ASL incidence after RT plus temozolomide for glioblastoma. An IMRT-based strategy is necessary to enhance treatment outcomes in the immune-oncology era.
Impact of regular magnetic resonance imaging follow-up after stereotactic radiotherapy to the surgical cavity in patients with one to three brain metastases.
Radiat Oncol. 2019; 14(1):45 [PubMed] Free Access to Full Article Related Publications
METHODS: We retrospectively analyzed patients who received SRS or HFSRT to the surgical cavity after resection of one to two BMs. Additional, non-resected BMs were managed with SRS alone. Survival was estimated by the Kaplan-Meier method. Prognostic factors were examined with the log-rank test and Cox proportional hazards model. Regular MRI FU was defined as performing a brain MRI 3 months after radiotherapy (RT) and/or performing ≥1 brain MRI per 180 days. Primary endpoint was local control (LC). Secondary endpoints were distant brain control (DBC), overall survival (OS) and the correlation between regular MRI FU and overall survival (OS), symptom-free survival (SFS), deferment of WBRT and WBRT-free survival (WFS).
RESULTS: Overall, 75 patients were enrolled. One, 2 and 3 BMs were seen in 63 (84%), 11 (15%) and 1 (1%) patients, respectively. Forty (53%) patients underwent MRI FU 3 months after RT and 38 (51%) patients received ≥1 brain MRI per 180 days. Median OS was 19.4 months (95% CI: 13.2-25.6 months). Actuarial LC, DBC and OS at 1 year were 72% (95% CI: 60-83%), 60% (95% CI: 48-72%) and 66% (95% CI: 53-76%), respectively. A planning target volume > 15 cm
CONCLUSION: Our results regarding oncological outcomes consist with the current data from the literature. Surprisingly, regular MRI FU did not result in increased OS, SFS, WFS or deferment of WBRT in our cohort consisting mainly of patients with a single and resected BM. Therefore, the impact of regular MRI FU needs prospective evaluation.
TRIAL REGISTRATION: Project ID: 2017-00033, retrospectively registered.
Risk factors to identify patients who may not benefit from whole brain irradiation for brain metastases - a single institution analysis.
Radiat Oncol. 2019; 14(1):41 [PubMed] Free Access to Full Article Related Publications
METHODS: We analyzed a total of 339 patient records with brain metastases treated with whole brain radiotherapy from January 2009 to January 2016. External beam radiotherapy techniques were used to deliver 33 Gy in 11 fractions (4 fractions per week) to the whole brain. Eight clinical factors with a potential influence on survival were investigated using the Kaplan-Meier method. All factors with a P < 0.05 in univariate analysis were entered into multivariate analysis using Cox regression.
RESULTS: In the present series of 339 patients, median survival time was 2.5 months (M; range, 0-61 months). Four risk factors Karnofsky Performance Score (KPS) < 70, age > 70, > 3 of metastases intracranial, uncontrolled primary tumor) were identified that were significant and negatively correlated with median survival time. Patients with no risk factors had a median survival of 4.7 M; one risk factor, 2.5 M; two risk factors, 2.3 M; and 3-4 risk factors, 0.4 M (p < 0.00001).
CONCLUSIONS: Patients with identified risk factors might have a negatively impacted overall survival after WBI. Accordingly, patients who will not benefit from WBI can be easily predicted if they have 3-4 of these risk factors.
Impact of overall corticosteroid exposure during chemoradiotherapy on lymphopenia and survival of glioblastoma patients.
J Neurooncol. 2019; 143(1):129-136 [PubMed] Related Publications
METHODS: GBM patients treated with CRT from 2007 to 2016 were retrospectively analyzed. Overall corticosteroid exposure was estimated as the average daily dexamethasone dose during 6 weeks of CRT. ASL was defined as grade 3 or higher lymphopenia within 3 months of starting CRT. ASL rates, overall survival (OS), and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Multivariable analysis (MVA) was performed using logistic and Cox regression to identify independent predictors of ASL and survival outcomes, respectively.
RESULTS: Of the 319 eligible patients, the median daily dexamethasone use was 2 mg/day. The high-dose dexamethasone cohort (> 2 mg/day) had significantly higher ASL and worse OS than the low-dose dexamethasone cohort: 3-month ASL of 43.7% versus 19.8% (p < 0.003) and median OS of 12.6 months versus 17.9 months (p < 0.001), respectively. On MVA, higher dexamethasone use was independently associated with higher ASL and worse OS, but not worse PFS. A subset analysis of patients with gross-total resection found that higher dexamethasone use was significantly associated with ASL, but not OS.
CONCLUSION: Increased corticosteroid use among GBM patients during CRT appears to be an independent risk factor for developing subsequent ASL. Its apparent association with worse OS may be influenced by other confounding factors and would need to be validated through prospective investigations.
Co-polysomy of 1p/19q in glial tumors: Retrospective analysis of 221 cases from single center.
Gene. 2019; 701:161-168 [PubMed] Related Publications
Cognitive rehabilitation for executive dysfunction in brain tumor patients: a pilot randomized controlled trial.
J Neurooncol. 2019; 142(3):565-575 [PubMed] Related Publications
METHODS: Twenty-five primary brain tumor survivors were randomized to GMT, an active control (Brain Health Program, BHP), or a wait-list (WAIT) control group. The BHP was a supportive care intervention offering education and activities to promote general brain health, without cognitive strategy training. Participants in GMT and BHP completed eight individual sessions and homework between sessions; those in WAIT received usual care. Assessments at baseline, immediately post-training, and 4-month follow-up used a battery of objective and subjective measures, including functional goal attainment.
RESULTS: Adherence (% sessions completed) was high for both GMT (98.9%) and BHP (84.4%). Executive functions improved with GMT but not BHP or WAIT (repeated measures analysis of variance, time-by-group interaction, post-training P = 0.077, follow-up P = 0.046). Both intervention groups reported fewer cognitive concerns at post-training (P = 0.049) and follow-up (P < 0.001). Functional goal attainment was greatest with GMT (post-training P = 0.027, follow-up P = 0.064).
CONCLUSIONS: GMT improved executive and real-life functioning in brain tumor survivors, with gains maintained at 4-month follow-up. Clinical implementation of this adaptable program merits consideration for clinically stable patients with cognitive dysfunction. Further development and larger prospective cognitive rehabilitation trials appear warranted.
Phase I/IIa study of concomitant radiotherapy with olaparib and temozolomide in unresectable or partially resectable glioblastoma: OLA-TMZ-RTE-01 trial protocol.
BMC Cancer. 2019; 19(1):198 [PubMed] Free Access to Full Article Related Publications
METHODS: The OLA-TMZ-RTE-01 study is a multicenter non-randomized phase I/IIa trial including unresectable or partially resectable GBM patients, from 18 to 70 years old. A two-step dose-escalation phase I design will first determine the recommended phase 2 dose (RP2D) of olaparib, delivered concomitantly with TMZ plus conventional irradiation for 6 weeks and as single agent for 4 weeks (radiotherapy period), and second, the RP2D of olaparib combined with adjuvant TMZ (maintenance period). Phase IIa will assess the 18-month overall survival (OS) of this combination. In both phase I and IIa separately considered, the progression-free survival, the objective response rate, the neurocognitive functions of patients, emotional disorders among caregivers, the survival without toxicity, degradation nor progression, the complications onset and the morphologic and functional MRI (magnetic resonance imaging) parameters will be also assessed as secondary objectives. Ancillary objectives will explore alteration of the DNA repair pathways on biopsy tumor, proton magnetic resonance spectroscopy parameters to differentiate tumor relapse and radionecrosis, and an expanded cognition evaluation. Up to 79 patients will be enrolled: 30 patients in the phase I and 49 patients in the phase IIa.
DISCUSSION: Combining PARP inhibitors, such as olaparib, with radiotherapy and chemotherapy in GBM may improve survival outcomes, while sparing healthy tissue and preserving neurocognitive function, given the replication-dependent efficacy of olaparib, and the increased PARP expression in GBM as compared to non-neoplastic brain tissue. Ancillary studies will help to identify genetic biomarkers predictive of PARPi efficacy as radiosensitizer.
TRIAL REGISTRATION: NCT03212742 , registered June, 7, 2017. Protocol version: Version 2.2 dated from 2017/08/18.
Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG): a phase III clinical study.
J Neurooncol. 2019; 143(1):107-113 [PubMed] Related Publications
METHODS: The study included patients between 3 and 20 years with clinically and radiologically confirmed DIPG. Primary endpoint was 6-month progression-free survival (PFS) following administration of nimotuzumab in combination with external beam radiotherapy (RT). Nimotuzumab was administered intravenously at 150 mg/m
RESULTS: All 42 patients received at least one dose of nimotuzumab in outpatient settings. Two patients had partial response (4.8%), 27 had stable disease (64.3%), 10 had progressive disease (23.8%) and 3 patients (7.1%) could not be evaluated. The objective response rate (ORR) was 4.8%. Median PFS was 5.8 months and median overall survival (OS) was 9.4 months. Most common drug-related AEs were alopecia (14.3%), vomiting, headache and radiation skin injury (7.1% each). Therapy-related serious adverse events (SAEs) were intra-tumoral bleeding and acute respiratory failure, which were difficult to distinguish from effects of tumor progression.
CONCLUSIONS: Concomitant treatment with RT and nimotuzumab was feasible in an outpatient setting. The PFS and OS were comparable to results achieved with RT and intensive chemotherapy in hospitalized setting.
Absolute numbers of regulatory T cells and neutrophils in corticosteroid-free patients are predictive for response to bevacizumab in recurrent glioblastoma patients.
Cancer Immunol Immunother. 2019; 68(6):871-882 [PubMed] Free Access to Full Article Related Publications
Quantifying radiation therapy response using apparent diffusion coefficient (ADC) parametric mapping of pediatric diffuse intrinsic pontine glioma: a report from the pediatric brain tumor consortium.
J Neurooncol. 2019; 143(1):79-86 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
MATERIALS AND METHODS: MR studies at baseline and post-RT in 95 DIPG patients were obtained and serial quantitative ADC parametric maps were generated from diffusion-weighted imaging based on T2/FLAIR and enhancement regions of interest (ROIs). Metrics assessed included total voxels with: increase in ADC (iADC); decrease in ADC (dADC), no change in ADC (nADC), fraction of voxels with increased ADC (fiADC), fraction of voxels with decreased ADC (fdADC), and the ratio of fiADC and fdADC (fDM Ratio).
RESULTS: A total of 72 patients were included in the final analysis. Tumors with higher fiADC between baseline and the first RT time point showed a trend toward shorter PFS with a hazard ratio of 6.44 (CI 0.79, 52.79, p = 0.083). In contrast, tumors with higher log mean ADC at baseline had longer PFS, with a hazard ratio of 0.27 (CI 0.09, 0.82, p = 0.022). There was no significant association between fDM derived metrics and overall survival.
CONCLUSIONS: Baseline ADC values are a stronger predictor of outcome compared to radiation related ADC changes in pediatric DIPG. We show the feasibility of employing parametric mapping techniques in multi-center studies to quantitate spatially heterogeneous treatment response in pediatric tumors, including DIPG.
Dose-painting multicenter phase III trial in newly diagnosed glioblastoma: the SPECTRO-GLIO trial comparing arm A standard radiochemotherapy to arm B radiochemotherapy with simultaneous integrated boost guided by MR spectroscopic imaging.
BMC Cancer. 2019; 19(1):167 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
METHODS/DESIGN: In this multicenter prospective phase III trial for newly diagnosed glioblastoma, 220 patients having undergone biopsy or surgery are planned for randomization to two arms. Arm A is the Stupp protocol (EBRT 60 Gy on contrast enhancement + 2 cm margin with concomitant temozolomide (TMZ) and 6 months of TMZ maintenance); Arm B is the same treatment with an additional simultaneous integrated boost of intensity-modulated radiotherapy (IMRT) of 72Gy/2.4Gy delivered on the MR spectroscopic imaging metabolic volumes of CHO/NAA > 2 and contrast-enhancing lesions or resection cavity. Stratification is performed on surgical and MGMT status.
DISCUSSION: This is a dose-painting trial, i.e. delivery of heterogeneous dose guided by metabolic imaging. The principal endpoint is overall survival. An online prospective quality control of volumes and dose is performed in the experimental arm. The study will yield a large amount of longitudinal multimodal MR imaging data including planning CT, radiotherapy dosimetry, MR spectroscopic, diffusion and perfusion imaging.
TRIAL REGISTRATION: NCT01507506 , registration date December 20, 2011.
A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma.
J Neurooncol. 2019; 142(3):537-544 [PubMed] Related Publications
METHODS: This open-label, single-arm phase II study treated recurrent TMZ-resistant GBM patients with standard monthly TMZ plus concurrent daily DSF 80 mg PO TID and Cu 1.5 mg PO TID. Eligible patients must have progressed after standard chemoradiotherapy and within 3 months of the last dose of TMZ. Known isocitrate dehydrogenase (IDH) mutant or secondary GBMs were excluded. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit (response or stable disease for at least 6 months), and safety.
RESULTS: From March 2017 to January 2018, 23 recurrent TMZ-resistant GBM patients were enrolled across seven centers, and 21 patients were evaluable for response. The median duration of DSF/Cu was 1.6 cycles (range: 0.1-12.0). The ORR was 0%, but 14% had clinical benefit. Median PFS was 1.7 months, and median OS was 7.1 months. Only one patient (4%) had dose-limiting toxicity (grade three elevated alanine transaminase).
CONCLUSIONS: Addition of DSF/Cu to TMZ for TMZ-resistant IDH-wild type GBM appears well tolerated but has limited activity for unselected population.
Perioperative holistic care more significantly reduces levels of anxiety and depression of pituitary tumor patients versus conventional care.
Medicine (Baltimore). 2019; 98(7):e14411 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.
Nat Med. 2019; 25(3):477-486 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma.
Nat Med. 2019; 25(3):470-476 [PubMed] Related Publications
Gamma Knife Stereotactic Radiosurgery favorably changes the clinical course of hemangioblastoma growth in von Hippel-Lindau and sporadic patients.
J Neurooncol. 2019; 142(3):471-478 [PubMed] Related Publications
METHODS: The authors reviewed a single-institution tumor registry to identify patients who had received GKRS for hemangioblastomas between January 1st, 1999, and December 31st, 2017.
RESULTS: 15 patients with 101 lesions met search criteria with a median age of first GKRS of 39.2 years (interquartile range [IQR] of 25.7-57.4 years), including 96 VHL and 5 sporadic lesions. The median time from GKRS to last follow-up was 5.4 years (IQR 2.3-11.5 years). 4 lesions (4%) and 3 patients (20%) experienced a local failure. The 1-year, 3-year, and 5-year freedom from new hemangioblastoma formation rates were 97%, 80%, and 46% respectively. Multivariate analysis revealed a reduction in tumor volume after GKRS. Several variables associated with a greater percent reduction in volume from GKRS to last follow-up: non-cystic status (p = .01), no prior craniotomy (p = .04), and follow-up time from GKRS (p < .0001).
CONCLUSIONS: GKRS is a successful long-term treatment option for hemangioblastomas changing the clinical course from saltatory growth to reduction in tumor volume. Non-cystic tumors and those without prior craniotomy were associated with a greater percent reduction in volume from GKRS at last follow-up.
The role of ABCB1 polymorphism as a prognostic marker for primary central nervous system lymphoma.
Ann Hematol. 2019; 98(4):923-930 [PubMed] Related Publications
A feasibility study of the Nativis Voyager
CNS Oncol. 2019; 8(1):CNS31 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
MATERIALS & METHODS: A total of 15 patients with rGBM were treated with one of two Voyager ultra-low radio frequency energy cognates: A1A or A2HU. Safety and clinical utility were assessed every 2-4 months.
RESULTS: Median overall survival was 8.04 months in the A1A arm and 6.89 months in the A2HU arm. No serious adverse events associated with Voyager were reported. No clinically relevant trends were noted in clinical laboratory parameters or physical exams.
CONCLUSION: The data suggest that the Voyager is safe and feasible for the treatment of rGBM.
Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma.
J Neurooncol. 2019; 142(3):455-462 [PubMed] Related Publications
METHODS: In this phase II study, according to a two stage design, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were considered eligible. Patients included were treated with ortataxel 75 mg/m
RESULTS: Between Nov 26, 2013 and Dec 12, 2015, 40 patients were recruited across six centres. The number of patients alive and free from progression at 6 months after the enrollment, observed in the first stage was four (11.4%), out of 35 patients included in the analysis, below the minimum number of events (7 out of 33) required to continue the study with the second stage The most important toxicities were neutropenia and hepatotoxicity that occurred in 13.2% of patients and leukopenia that occurred in 15.8% of patients.
CONCLUSION: Overall ortataxel treatment fail to demonstrate a significant activity in recurrent GBM patients. However in a limited number of patients the drug produced a benefit that lasted for a long time.
TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT01989884.
Targeted next-generation sequencing panel (TruSight Tumor 170) in diffuse glioma: a single institutional experience of 135 cases.
J Neurooncol. 2019; 142(3):445-454 [PubMed] Related Publications
METHODS: We analyzed 135 samples of DG, which were diagnosed by WHO criteria based on histological features and conventional molecular tests including immunostaining, 1p/19q FISH, and analysis of MGMT methylation and TERT promoter mutation.
RESULTS: A total of 135 cases consisted of 38 IDH-mutant [17 astrocytoma (AC), 13 oligodendroglioma (OD) and eight glioblastoma (GBM)], 87 IDH-wildtype (six AC, three OD and 78 GBM), and 10 diffuse midline glioma, H3K27M-mutant. DNA analysis enabled the detection of all mutations identified in these samples by conventional techniques, and the results were highly comparable to the known mutations in each subtype. RNA analysis detected four fusion genes including PTPRZ1-MET, FGFR3-TACC3, FAM131B-BRAF, and RET-CCDC6 and one splicing variant (EGFR vIII mutant). Clustered copy number loss in 1p and 19q loci genes were detected in 1p/19q-codeleted OD.
CONCLUSIONS: The application of TST-170 panel based NGS in clinical and laboratory setting is expected to improve diagnostic accuracy and prognostication. Most benefits are expected in IDH-wildtype DG, a group of genetically heterogenous tumors harboring DNA sequence changes, copy number alterations, and fusions in a large number of oncogenes and tumor suppressor genes.
Outcome of children with Langerhans cell histiocytosis and single-system involvement: A retrospective study at a single center in Shanghai, China.
Pediatr Hematol Oncol. 2018 Oct - Nov; 35(7-8):385-392 [PubMed] Related Publications
PROCEDURE: 60 evaluable newly diagnosed patients (37 boys, 23 girls) with a median age of 3.9 years (range: 0.3-15.3 years) and histiopathology-confirmed SS-LCH were enrolled from 2010 to 2014. All patients received systemic chemotherapy using either the DAL HX-83 or LCH-II protocol as determined by the physician.
RESULTS: Bone was the most frequently affected organ (56/60, 93.3%). Of the 56 patients suffering from SS-bone disease, 35 (62.5%) had unifocal disease and 21 (37.5%) had multifocal disease. CNS-risk lesions were seen in nine patients (16.1%, 9/56) at diagnosis. Thirty-two patients were treated with the LCH-II protocol and 28 received the DAL HX-83 protocol. No patient received intralesional steroid injection at the time of surgery. CNS-risk lesion correlated with an inferior event-free survival (EFS) for patients with bone disease (62.5 ± 17.1% vs. 90.7 ± 4.5%; p = 0.039). The difference in the 5-year EFS between patients with unifocal and multifocal SS-bone LCH did not reach the statistical significance (93.8 ± 4.3% vs. 75.0 ± 9.7%; p = 0.074). No deaths were observed, leading to a 5-year OS of 100% in the present cohort of patients. Permanent consequences and secondary malignancies were not observed but were also limited by short follow-up.
CONCLUSIONS: Optimal therapy for patients with SS-bone LCH has not been established. Less toxic therapeutic approaches should be considered for these patients and tested in prospective trials.
Effects of 5-ALA dose on resection of glioblastoma.
J Neurooncol. 2019; 141(3):523-531 [PubMed] Related Publications
METHODS: A retrospective cohort study for patients who participated in a phase I and II dose-escalation clinical trial on 5-ALA for resection of HGG. A total of 25 patients were found to have newly diagnosed glioblastoma on histology and enrolled in our study. Patients receiving low doses of 5-ALA (10-30 mg/kg) (n = 6) were compared to those receiving high doses (40-50 mg/kg) (n = 19). Pre- and post-operative contrast enhanced T1W MRI were evaluated with volumetric analysis.
RESULTS: Median RTV was 0.69 cm
CONCLUSIONS: High doses of 5-ALA FGS are associated with less RTV and greater probability of GTR. 5-ALA dose was not associated with OS. Further studies with a larger patient cohort are warranted.
Incidence of Hippocampal Metastases: Laterality and Implications for Unilateral Hippocampal Avoiding Whole Brain Radiotherapy.
Biomed Res Int. 2018; 2018:2459608 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
Method: The aim of this retrospective study is to describe spatial distribution of brain metastases on MRI in a cohort of 260 patients (2595 metastases) and to evaluate distribution separately in the left and right hippocampus and in respective hippocampal avoiding zones (HAZ, region with subtherapeutic radiation dose), including evaluation of location of metastatic mass centre.
Results: The median number of brain metastases was three, with lung cancer being the most common type of primary tumour; 36% had single metastasis. Almost 8% of patients had metastasis within hippocampus (1.1% of all metastases) and 18.1% of patients within HAZ (3.3% of all metastases). No statistically significant difference was observed in the laterality of hippocampal involvement, also when the location of centre of metastases was analyzed. There were more patients presenting the centre of metastasis within left (15) versus right (6) HAZ approaching the borderline of statistical significance.
Conclusion: No significant difference in the laterality of BM seeding within hippocampal structures was observed. The hypothesized unilateral sparing WBRT would have theoretical advantage in about 50% reduction in the risk of subsequent recurrence within spared regions.
Eur J Nucl Med Mol Imaging. 2019; 46(3):558-568 [PubMed] Related Publications
METHODS: Patients with histologically proven glioblastoma or brain metastases were prospectively included in this monocentric clinical trial (IMOTEP). Patients were included either due to a clinical suspicion of relapse or to assess residual tumor infiltration after treatment. Multimodality brain MRI and
RESULTS: One hundred six cases were prospectively investigated by the MNTB. All patients with brain metastases (N = 41) had a clinical suspicion of recurrence. The addition of
Outcomes of re-irradiation for brain recurrence after prophylactic or therapeutic whole-brain irradiation for small cell lung Cancer: a retrospective analysis.
Radiat Oncol. 2018; 13(1):258 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
MATERIALS AND METHODS: Eighty-five patients with SCLC and brain recurrence after prophylactic or therapeutic WBI in 1998-2015 were identified and data were extracted from the medical records. Survival was estimated with the Kaplan-Meier method, and univariate and multivariate Cox proportional hazards modeling was used to identify factors associated with OS or further brain progression.
RESULTS: Brain recurrence was treated by stereotactic radiosurgery (SRS) in 33 patients (39%), repeat WBI in 14 (16%), chemotherapy-only in 16 (19%), and observation in 22 (26%). Median OS time after brain recurrence (OSrec) was 4.3 months for all patients; 6-month OSrec rates were 58% after SRS, 21% after repeat WBI, 50% after chemotherapy-only, and 5% after observation (P < 0.001). Inferior OSrec was associated with poor performance status (ECOG score ≥ 3) and uncontrolled extracranial disease. Superior OSrec was associated with receipt of ≥4 chemotherapy cycles before brain recurrence and receipt of chemotherapy, SRS, or repeat WBI afterward. Receipt of chemotherapy after brain recurrence correlated with brain progression.
CONCLUSIONS: Some patients with brain recurrence after WBI for SCLC can survive for extended periods with appropriate intervention, especially those with adequate performance status or controlled extracranial disease.
Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial.
Radiat Oncol. 2018; 13(1):252 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
METHODS: This prospective, single arm, phase II trial will recruit patients with up to 4 brain metastases and at least one resectable lesion. All lesions will be treated with SRS and symptomatic lesions will be resected within 1-4 days after SRS. Patients will be monitored for 6-month local control, in-brain progression free survival, distant in-brain failure, rate of leptomeningeal spread, radiation necrosis and overall survival. Additionally, we will also perform correlative radiobiological molecular studies to assess the effect of radiation dosing on the tumor tissue and clinical outcomes. We expect that pre-operative SRS to the gross tumor prior to surgical resection will improve local control and decrease leptomeningeal failure.
DISCUSSION: Our study is the second prospective trial to investigate the efficacy of pre-operative SRS in the treatment of multiple BMs. In addition, the correlative molecular studies will be the first to investigate early response of BMs at a cellular and genetic level in response to radiation doses and potentially provide molecular prognostic markers for local control and overall survival.
TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03398694 (registration date: January 12, 2018).
Additional radiation boost to whole brain radiation therapy may improve the survival of patients with brain metastases in small cell lung cancer.
Radiat Oncol. 2018; 13(1):250 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
METHODS: A total of 82 SCLC patients who were found to have BMs treated with WBRT plus a radiation boost (n = 33) or WBRT-alone (n = 49) from January 2008 to December 2015 were retrospectively analyzed. All patients were limited-stage (LS) SCLC at the time of the initial diagnosis, and none of them had extracranial metastases prior to detection of BMs. The primary end point was OS.
RESULTS: The median OS for all of the patients was 9.6 months and the 6-, 12- and 24-months OS rates were 69.1, 42.2 and 12.8%, respectively. At baseline, the proportion of more than 3 BMs was significantly higher in the WBRT group than in the WBRT plus boost group (p = 0.0001). WBRT plus a radiation boost was significantly associated with improved OS in these patients when compared with WBRT-alone (13.4 vs. 8.5 months; p = 0.004). Further, the survival benefit still remained significant in WBRT plus boost group among patients with 1 to 3 BMs (13.4 vs. 9.6 months; p = 0.022).
CONCLUSION: Compared with WBRT-alone, the use of WBRT plus a radiation boost may prolong survival in SCLC patients with BMs. The dose escalation strategy in brain radiotherapy for selected BMs patients with SCLC should be considered.
An early feasibility study of the Nativis Voyager
CNS Oncol. 2019; 8(1):CNS30 [PubMed] Article available free on PMC after 01/05/2020 Related Publications
MATERIALS & METHODS: Voyager is a noninvasive, nonthermal, nonionizing and portable investigational device which delivers ultra-low radio frequency energy (ulRFE
RESULTS: Data from the first 11 patients treated are reported here. Median progression-free survival was 10 weeks in the V arm and 16 weeks in the V + SoC arm. Median overall survival was 16 months in V arm and 11 months in the V + SoC arm. No serious adverse events associated with the device were reported.
CONCLUSION: These data suggest that the Voyager is safe and feasible for the treatment of rGBM.