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Stereotactic Body Radiation Therapy (SBRT) is a standard of care for many localizations but the question of the optimal fractionation remains a matter of concern. If single fraction sessions are routinely used for intracranial targets, their utilization for mobile extracranial lesions is a source of debate and apprehension. Single session treatments improve patient comfort, provide a medico-economic benefit, and have proven useful in the context of the SARS-CoV 2 pandemic. However, both technical and radiobiological uncertainties remain. Experience from intracranial radiosurgery has shown that the size of the target, its proximity to organs at risk, tumor histology, and the volume of normal tissue irradiated are all determining factors in the choice of fractionation. The literature on the use of single fraction for extracranial sites is still scarce. Only primary and secondary pulmonary tumors have been evaluated in prospective randomized trials, allowing the integration of these fractionation schemes in daily practice, for highly selected cases and in trained teams. The level of evidence for the other organs is mainly based on dose escalation or retrospective trials and calls for caution, with further studies being needed before routine use in clinical practice.

Aims: FAST-Forward and UK-FAST-trials have demonstrated the safety and efficacy of five-fraction breast adjuvant radiation therapy (RT) and have become the standard of care for selected early breast cancer patients. In response to the additional burden caused by the COVID-19 pandemic, we implemented "One-Week Breast RT," an innovative program delivering five-fraction whole breast RT in a complete 5-day workflow. The primary objective of this study was to demonstrate the feasibility and safety of our program. The secondary objective was to evaluate cosmetic results., Material and Methods: A total of 120 patients treated from February 2021 to March 2022, received whole breast RT without lymph node irradiation nor boost, with 26 Gy in five fractions over one week. Inverse planning with restricted optimization parameters offers systematic deep inspiration breath-hold aimed to provide treatment plans compliant with FAST-Forward recommendations. Toxicity and cosmetic evaluations were prospectively registered prior (pre-RT), at the end (end-RT), and 6 months after RT (6 months) based on Common Terminology Criteria for Adverse Events v. 4.03 and Harvard scale., Results: With a median age of 70 years (interquartile range (IQR): 66-74) and a median follow-up of 6 months (IQR: 6.01-6.25), most patients (93.3%) completed their RT in one week from baseline to the end of the treatment consultation. The most common acute toxicities (at end-RT) were skin-related: radio-dermatitis (72%), induration (35%), hyperpigmentation (8%), and breast edema (16%). The rate of radio-dermatitis decreased from end-RT to 6 months (71.7% vs 5.4%, P< 0.001). No patient experienced grade ≥3 toxicity. At 6 months, cosmetic results were generally good or excellent (94.1%)., Conclusion: This study confirms the feasibility and acute safety of the "One-Week Breast RT" in real life. Favorable toxicity profiles and good cosmetic outcomes are in line with FAST-Forward results. A prospective national cohort, aimed at decreasing treatment burden, maintaining safety, efficacy, and improving RT workflow efficiency with longer follow-up is ongoing., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Immuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the colorectal (CRC) cohort analysis from the SABR-PDL1 trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in advanced cancer patients., Methods: Eligible patients received atezolizumab 1200 mg every 3 weeks until progression or unmanageable toxicity, together with ablative SBRT delivered concurrently with the 2nd cycle (recommended dose of 45 Gy in 3 fractions, adapted upon normal tissue tolerance constraint). SBRT was delivered to at least one tumor site, with at least one additional measurable lesion being kept from the radiation field. The primary efficacy endpoint was one-year progression-free survival (PFS) rate from the start of atezolizumab. Sequential tumor biopsies were collected for deep multi-feature immune profiling., Results: Sixty pretreated (median of 2 prior lines) advanced CRC patients (38 men [63%]; median age, 59 years [range, 20-81 years]; 77% with liver metastases) were enrolled in five centers (France: n = 4, Spain: n = 1) from 11/2016 to 04/2019. All but one (98%) received atezolizumab and 54/60 (90%) received SBRT. The most frequently irradiated site was lung (n = 30/54; 56.3%). Treatment-related G3 (no G4-5) toxicity was observed in 3 (5%) patients. Median OS and PFS were respectively 8.4 [95%CI:5.9-11.6] and 1.4 months [95%CI:1.2-2.6], including five (9%) patients with PFS > 1 year (median time to progression: 19.2 months, including 2/5 MMR-proficient). Best overall responses consisted of stable disease (n = 38; 64%), partial (n = 3; 5%) and complete response (n = 1; 2%). Immune-centric multiplex IHC and RNAseq showed that SBRT redirected immune cells towards tumor lesions, even in the case of radio-induced lymphopenia. Baseline tumor PD-L1 and IRF1 nuclear expression (both in CD3 + T cells and in CD68 + cells) were higher in responding patients. Upregulation of genes that encode for proteins known to increase T and B cell trafficking to tumors (CCL19, CXCL9), migration (MACF1) and tumor cell killing (GZMB) correlated with responses., Conclusions: This study provides new data on the feasibility, efficacy, and immune context of tumors that may help identifying advanced CRC patients most likely to respond to immuno-radiotherapy., Trial Registration: EudraCT N°: 2015-005464-42; Clinicaltrial.gov number: NCT02992912., (© 2024. The Author(s).)

Stereotactic Body Radiation Therapy (SBRT) is a standard of care for many localizations but the question of the optimal fractionation remains a matter of concern. If single fraction sessions are routinely used for intracranial targets, their utilization for mobile extracranial lesions is a source of debate and apprehension. Single session treatments improve patient comfort, provide a medico-economic benefit, and have proven useful in the context of the SARS-CoV 2 pandemic. However, both technical and radiobiological uncertainties remain. Experience from intracranial radiosurgery has shown that the size of the target, its proximity to organs at risk, tumor histology, and the volume of normal tissue irradiated are all determining factors in the choice of fractionation. The literature on the use of single fraction for extracranial sites is still scarce. Only primary and secondary pulmonary tumors have been evaluated in prospective randomized trials, allowing the integration of these fractionation schemes in daily practice, for highly selected cases and in trained teams. The level of evidence for the other organs is mainly based on dose escalation or retrospective trials and calls for caution, with further studies being needed before routine use in clinical practice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Background: Recent studies showed that patients with glioma can safely participate in early phase clinical trials; however, clinical benefits in this population were limited. We aimed to evaluate the benefit of molecular profiling to guide enrolment in early phase trials for patients with recurrent glioma., Methods: Records of patients enrolled in early phase trials of cytotoxic therapies, small molecule inhibitors or monoclonal antibodies from 2008 to 2018 were reviewed for clinico-pathological characteristics, toxicity, response, progression-free survival and overall survival (OS). The primary objective was to evaluate response rates in molecularly-oriented versus non-molecularly-oriented patients., Results: Eighty-eight patients were enrolled, of whom 45 (51.1%) patients were molecularly-oriented. Targets included IDH1/2 (n = 15), BRAF (n = 11), and FGFR1 (n = 3) mutations, FGFR2-3 fusions (n = 9), and mismatch repair deficiency (n = 7). Among patients with high-grade glioma (n = 74), the rate of stable disease ≥6 months and partial or complete response was 25.7% in molecularly-oriented versus 5.1% in non-molecularly-oriented patients (p = 0.02). Upon multivariable adjustment, baseline steroid use ≥20 mg prednisone equivalent per day was associated with shorter OS (OR 3.15 [95% CI 1.62-6.13], p = 0.0008), while molecular enrichment strategy was associated with longer OS (OR 0.40 [95% CI 0.22-0.73], p = 0.003). Nine (10.2%) patients experienced grade 3-4 toxicity and no dose limiting toxicity (DLT) occurred in both cohorts., Conclusion: The use of molecular profiling to guide enrolment in early phase trials is feasible and might provide benefits to selected patients with glioma. Further studies are warranted to confirm these results in larger randomised settings and identify the patients most likely to benefit from this approach., Competing Interests: Conflict of interest statement CB reports personal fees from BMS, Sanofi, Abbvie, Roche, Astra Zeneca. As a subinvestigator at the DITEP: Abbvie, Aduro biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, Astra Aeneca, Astra Zeneca Ab, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boehringer Ingel-heim, Boston Pharmaceuticals, Inc, Bristol Myers Squibb, Bristol-Myers Squibb Inter-national Corporation, Ca, Celgene Corpo-ration, Cephalon, Chugai Pharmaceutical Co, Clovis Oncology, Daiichi Sankyo, Debiopharm S.a, Eisai, Eli lilly, Exelixis, Forma, Gamamabs, Genentech, Inc, Gilead Sciences, Inc, Glaxosmithkline, Glenmark Pharmaceuticals, H3 Biomedicine, Inc, Hoffmann La Roche Ag, Incyte Corpora-tion, Innate Pharma, Institut De Recher-che Pierre Fabre, Iris Servier, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev., Inc, Lilly France, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Kgaa, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Mil-lennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Nerviano Medical Sciences, Novartis Pharma, Octimet Onco-logy Nv, Oncoethix, Oncomed, Oncopep-tides, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, Pharma Mar, Pierre Fabre Medicament, Plexxikon, Rigontec Gmbh, Roche, Sanofi Aventis, Sierra Oncology, Taiho Pharma, Tesaro, Tioma Therapeutics, Wyeth Pharma-ceuticals France, Xencor, Y's Therapeutics. JCS is an employee of Amgen and former employee of AstraZeneca. FB reports research funding from Abbvie and Sanofi; employment from Celgene (I); stocks from Crossject (I); travel, accommodations, expenses from Bristol-Myers Squibb for travel expenses, outside the submitted work. KHX reports consulting fees and research grant from BTG, outside the submitted work. AI reports grants and other from Carthera (September 2019); research grants from Transgene; grants from Sanofi, and Air Liquide; and travel funding from Leo Pharma, outside the submitted work. MT reports research funding from Sanofi; consulting or advisory role from Agios Pharmaceutical, Integragen, Taiho Oncology, and Servier, outside the submitted work; travel, accommodations, expenses from Merck Sharp & Dome and Servier, outside the submitted work. All remaining authors have declared no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The vertebrate left-right axis is specified during embryogenesis by a transient organ: the left-right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left-right organizer metallopeptide (CIROP). Here, we show that CIROP is specifically expressed in ciliated LROs. In zebrafish and Xenopus, CIROP is required solely on the left side, downstream of the leftward flow, but upstream of DAND5, the first asymmetrically expressed gene. We further ascertained 21 human patients with loss-of-function CIROP mutations presenting with recessive situs anomalies. Our findings posit the existence of an ancestral genetic module that has twice disappeared during vertebrate evolution but remains essential for distinguishing left from right in humans., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Due to the continuously increasing number of newly diagnosed breast cancer and limited health resources hypofractionated radiotherapy is a major topic. Recent results from randomized clinical trials assessing extreme hypofractionated radiotherapy for whole or partial breast radiotherapy are practice changing. Here we report toxicity and oncological outcomes from major recent trials of extreme hypofractionated breast irradiation and present an ongoing prospective implementation program. For whole breast irradiation, with a 10 years follow up, the UK-FAST trial demonstrated no significant difference in toxicity between a once weekly 5 fractions (5,7Gy/fr) regimen and a conventional 50Gy/25fr regimen. With a 5 years follow up, the FAST-Forward trial showed non inferiority on local control for a 5 fractions over 1 week (5,2Gy/fr) regimen versus standard 40Gy/15fr over 3 weeks with safe toxicity profile. For accelerated partial breast irradiation, in low-risk breast cancers patients, several phase III randomized trials confirmed that extreme hypofractionation is a valid option. With our "One Week Breast Radiotherapy" program, we propose the implementation of a one-week full workflow preparing and delivering 5 fractions over 1 week (26Gy) in selected patients with prospective follow-up. Several extreme hypofractionated breast radiotherapy regimens are validated and can be routinely discussed with patients in a share decision-making process following patient selection criteria and dosimetric constraints., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Due to a steadily growing use of stereotactic radiotherapy (SRT) for treatment of brain metastases (BMs), the in-field failure after an initial stereotaxy is an increasingly frequent problem. Repeat stereotactic radiotherapy (re-SRT) shows encouraging results in terms of local control. However, the evidence on prognostic factors limiting the overall survival (OS) of re-treated patients is scarce. Here, we sought to analyze the patients' and treatment characteristics influencing the survival outcomes after re-SRT., Methods: Data of all patients with local failure of initial SRT treated from 2012 to 2019 were retrospectively reviewed and cases treated with salvage SRT were analyzed. We analyzed the impact of patients' and treatment characteristics on overall survival after re-SRT by Kaplan-Meier method and Cox regression models. Local and distant brain control, cause of death, and radionecrosis rate were also assessed., Results: Forty-seven patients with 55 BMs treated with re-SRT were evaluated. Median OS after re-SRT was 9.2 months and the overall local control was 83.6%. Nine BMs (16.4%) presented local relapse (LR), 12 (21.8%) radionecrosis, while 21 patients (44.7%) developed new BMs. Only absence of extracranial metastases at BMs diagnosis (HR 0.42, CI 95%; 0.18-0.97), extracranial disease progression (HR 2.39, CI 95%; 1.06-5.38) and distant brain failure (HR 3.94, CI 95%; 1.68-9.24) after re-SRT were significantly associated with patients' survival. Extracranial progression following re-SRT was an independent prognosticator of worse OS., Conclusion: Re-SRT after LR presented excellent local control with acceptable RN rate and improved patients' survival, limited mainly by extracranial and distant brain progression.

Background: Poor Performance Status (PS) of cancer patients, defined as PS score 2-3, is an impediment for many drug- and irradiation-based treatments, supported by the trials that exclude subjects with PS < 1. Reports on the benefits of stereotactic radiotherapy (SRT) for brain metastases (BMs) in poor PS patients are scarce. We sought to review the characteristics and survival outcomes of this cohort, to assess who may benefit most from SRT., Methods: We retrospectively evaluated 73 patients with PS 2 or 3 (63 and 10 cases) treated with SRT for 150 BMs from 2012 to 2018. Patients' characteristics and post-SRT survival, stratified by concomitant systemic treatment (CST) were assessed using the Kaplan-Meier method (p-value < 0.05)., Results: Non-small cell lung cancer was the most frequent primary tumor. Extracranial metastases were present in 86.3% of patients. The median overall survival (mOS) after SRT was estimated as 6.0 months (range 0.2-37.7), with 6- and 12-month survival rates of 51.0% and 21.0%, respectively. CST was administrated to 59.7% of patients (immunotherapy, target therapy or chemotherapy). Patients treated with CST presented larger mOS (6.7 vs. 4.4 months for patients treated with SRT alone, p = 0.3), and better 6- and 12-month survival rates (59% and 24% vs. 37% and 18% in patients not treated with CST)., Conclusions: Survival rate after SRT for BMs in poor performance patients, especially with PS 2, can justify SRT, in particular if an effective systemic treatment is available. Both SRT and CST should be more accessible for these patients in clinical practice.

Background: Combining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions., Methods: Clinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient's response., Results: A total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables., Conclusions: These results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT., Competing Interests: Competing interests: RS received travel and accommodation expenses from AstraZeneca. NS reports travel grants from Merck Sharpe & Dohme, Astellas, Bayer and Bristol-Myers Squibb. MH declares consulting fees, research grants and travel expenses from Merck Serono, MSD, Novartis, BMS and Teva. PO reports research grants from Merck Sharpe & Dohme, Astellas and Janssen; travel grants from Ipsen and Ferring Pharmaceuticals and honorarium from Ferring and Bayer. CR received research grants from Therapanacea and Elekta. CF is a full-time employee of AstraZeneca since September 2017. NP reports grants from GE, Biogen and consulting fees from AstraZeneca and Ipsen. J-CS reports consultancy fees from AstraZeneca, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, PharmaMar, Pierre Fabre, Roche-Genentech, Sanofi, Servier, Symphogen, Takeda. J-CS has been Full time employee for AstraZeneca (September 2017–December 2019) and is a shareholder of AstraZeneca, Gritstone. CF received travel, accommodations, expenses from Amgen; Genentech; GlaxoSmithKline; MedImmune. CM is an advisory board member, speaker, investigator at Amgen, Astellas, AstraZeneca, Bayer, Celgene, Genentech, Ipsen, Janssen, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, Orion. USG received support for presentation activities for Dr Sennewald Medizintechnik GmbH, has received support for investigator initiated clinical studies (IITs) from MSD and AstraZeneca and contributed at Advisory Boards Meetings of AstraZeneca and Bristol-Myers Squibb. RF received grants/research support from MSD; AstraZeneca; Merck (Germany/Darmstadt); Novocure; honoraria/consultation fees: MSD; AstraZeneca; Merck (Germany/Darmstadt); Novocure; Fresenius and reports participation in a company sponsered speakers bureau: AstraZeneca; MSD; Merck (Germany/Darmstadt); Sennewald; Novocure; Brainlab; Roche. ED has declared consulting fees and support from Roche, BMS, Boehringer, AstraZeneca, Lilly Amgen and Merck-Serono., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Aim: The aims of the present study were to describe treatment patterns and survival outcomes in patients with central nervous system metastases (CNSM) selected among metastatic breast cancer (MBC) patients included in a retrospective study from the Epidemiological Strategy and Medical Economics (ESME) MBC cohort., Methods: Neurological progression-free survival (NPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Significant contributors to NPFS were determined using a multivariate Cox proportional hazards model., Results: After a median follow-up of 42.8 months, of 16 701 patients included in the ESME MBC database, CNSM were diagnosed in 24.6% of patients. The most frequent treatments after diagnosis of CNSM were whole-brain radiotherapy (WBRT) (45.2%) and systemic treatment (59.3%). Median OS and NPFS were 7.9 months (95% CI: 7.2-8.4) and 5.5 months (95% CI: 5.2-5.8), respectively. In multivariate analysis, age >70 years (vs <50 years; HR = 1.40; 95% CI: 1.24-1.57), triple-negative tumours (vs HER2-/HR+; HR = 1.87; 95% CI: 1.71-2.06), HER2+/HR-tumours (vs HER2-/HR+; HR = 1.14; 95% CI: 1.02-1.27), ≥3 metastatic sites (vs < 3; HR = 1.32; 95% CI: 1.21-1.43) and ≥3 previous treatment lines (vs < 3; HR = 1.75; 95% CI: 1.56-1.96) were detrimental for NPFS. A time interval between selection and CNSM diagnosis superior to 18 months (vs <9 months; HR = 0.88; 95% CI: 0.78-0.98) was associated with longer NPFS., Conclusions: This study describes current treatment patterns of MBC patients in a "real life" setting. Despite advances in stereotactic radiation therapy, most of the patients still received WBRT. More research is warranted to identify patient subsets for tailored treatment strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Metastatic breast cancer (MBC) behaviour differs depending on hormone receptors (HR) and human epidermal growth factor receptor (HER2) statuses., Methods: The kinetics of central nervous system (CNS) metastases (CNS metastasis-free survival, CNSM-FS) and subsequent patient's prognosis (overall survival, OS) according to the molecular subtype were retrospectively assessed in 16703 MBC patients of the ESME nationwide multicentre MBC database (Kaplan-Meier method)., Results: CNS metastases occurred in 4118 patients (24.6%) (7.2% at MBC diagnosis and 17.5% later during follow-up). Tumours were HER2-/HR+ (45.3%), HER2+/HR+ (14.5%), HER2+/HR- (14.9%) and triple negative (25.4%). Median age at CNS metastasis diagnosis was 58.1 years (range: 22.8-92.0). The median CNSM-FS was 10.8 months (95% CI: 16.5-17.9) among patients who developed CNS metastases. Molecular subtype was independently associated with CNSM-FS (HR = 3.45, 95% CI: 3.18-3.75, triple-negative and HER2-/HR+ tumours). After a 30-month follow-up, median OS after CNS metastasis diagnosis was 7.9 months (95% CI: 7.2-8.4). OS was independently associated with subtypes: median OS was 18.9 months (HR = 0.57, 95% CI: 0.50-0.64) for HER2+/HR+ , 13.1 months (HR = 0.72, 95% CI: 0.65-0.81) for HER2+/HR-, 4.4 months (HR = 1.55, 95% CI: 1.42-1.69) for triple-negative and 7.1 months for HER2-/HR+ patients (p <0.0001)., Conclusions: Tumour molecular subtypes strongly impact incidence, kinetics and prognosis of CNS metastases in MBC patients., Clinical Trial Registration: NCT03275311.

Purpose: To evaluate a strategy that used thermal-ablation of vertebral metastases (VM) to prevent vertebral related events (VRE) in patients with differentiated thyroid cancer (DTC)., Methods: This single center study retrospectively reviewed records and post-operative imaging of all DTC patients treated with thermal-ablation for asymptomatic VMs. Rate of local tumor control at first post-operative imaging, 12 and 24 months after thermal-ablation and rate of VREs at 12 and 24 months among the treated VMs were reported. New VMs that occurred during the follow-up and were not considered for additional thermal-ablation were moniroted and VREs were reported., Results: Thermal-ablation was used to achieve local control of 41 VMs in 28 patients. Median post-treatment follow-up was 22 months [range: 12-80] and the mean delay for first post-operative imaging was 2 months [range: 0.6-7.5]. Local control at first post-operative imaging, 12 and 24 months was achieved in 87.8%, 82.9% and 75.6%, respectively. Among the treated VMs the rates of VRE was 7.3% at 2 years, significantly lower if local control was achieved at first post-operative imaging than if it was not (0% vs 30%, p = 0.011, OR = 0.184 [95%CI = 0.094-0.360]). After thermal-ablation procedures, 19 news VMs occurred in 11 patients (39.2%) with a median interval of 8 months [range 1-26] and remained untreated. Among these untreated VMs, the rate of VREs at 2 years was significantly higher compared to the treated VMs: (36.8% vs. 7.3%, p = 0.008, OR = 0.135, [95%CI = 0.030-0.607])., Conclusion: local tumor control of VMs using thermal-ablation decreases the risk of VREs in DTC patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Immunotherapy in Glioblastomas: Targeting the immune system as a therapeutic strategy in solid tumors has shown great efficacy in various tumor types. However the role and success of this approach in glioblastomas remain to be determined. Recent studies demonstrated that central nervous system is no longer considered as an immunoprivileged sanctuary with impressive immune response without blood brain barrier's disruption. Improving our understanding of immune privilege in the central nervous system could lead to better treatment strategies in gliobastomas. This review focuses on describing the immune system in the central nervous system and immuno-therapeutic strategies under development in glioblastomas., (© 2018 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)

As the prognosis of metastatic non-small cell lung cancer (NSCLC) patients is constantly improving with advances in systemic therapies (immune checkpoint blockers and new generation of targeted molecular compounds), more attention should be paid to the diagnosis and management of treatments-related long-term secondary effects. Brain metastases (BM) occur frequently in the natural history of NSCLC and stereotactic radiation therapy (SRT) is one of the main efficient local non-invasive therapeutic methods. However, SRT may have some disabling side effects. Brain radiation necrosis (RN) represents one of the main limiting toxicities, generally occurring from 6 months to several years after treatment. The diagnosis of RN itself may be quite challenging, as conventional imaging is frequently not able to differentiate RN from BM recurrence. Retrospective studies have suggested increased incidence rates of RN in NSCLC patients with oncogenic driver mutations [epidermal growth factor receptor (EGFR) mutated or anaplastic lymphoma kinase (ALK) positive] or receiving tyrosine kinase inhibitors. The risk of immune checkpoint inhibitors in contributing to RN remains controversial. Treatment modalities for RN have not been prospectively compared. Those include surveillance, corticosteroids, bevacizumab and local interventions (minimally invasive laser interstitial thermal ablation or surgery). The aim of this review is to describe and discuss possible RN management options in the light of the newly available literature, with a particular focus on NSCLC patients.

Gene fusions of EWSR1 with members of the CREB family of transcription factors (CREB1, ATF1, and CREM) have recently been described in exceptional intracranial myxoid mesenchymal tumors. Although this is a known gene fusion found in various mesenchymal tumors, EWSR1 fusion with CREM has only been observed in 3 intracranial myxoid tumors. In this paper, we present 1 such tumor with in-depth histopathological description and long-term follow-up. There is controversy regarding whether these tumors represent a novel entity or simply an intracranial localization of the myxoid variant of angiomatoid fibrous histiocytoma, a rare soft tissue tumor of the extremities. Out of 11 cases mentioned in the literature, the 3 isolated case reports by Dunham et al, Ochalski et al, and Alshareef et al are designated as angiomatoid fibrous histiocytoma, whereas the others are defined as a novel tumoral entity called intracranial myxoid mesenchymal tumor with EWSR1-CREB fusion. We believe the vast morphological and immunohistochemical spectrum of angiomatoid fibrous histiocytoma makes it difficult to dismiss this diagnosis.

Objective: To study the prognostic value of neutrophil disorders in a retrospective cohort of high-grade glioma patients receiving definitive concurrent temozolomide and radiation., Materials and Methods: Clinical records of consecutive patients treated in our Institution between January 2005 and December 2010 with concurrent temozolomide (75 mg/m 2 daily) and radiation were collected. The prognostic value of pretreatment neutrophilia on survival, defined as a neutrophil count exceeding 7 G/L, was examined., Results: We identified 164 patients, all treated with concurrent temozolomide-based chemoradiotherapy. Initial surgery was achieved in most (75%), with resection > 90% in 55 patients (34%). Total 151 patients (92%) had glioblastoma, and 13 patients (8%) had WHO grade III glioma. Eighty-two patients (50%) displayed pretreatment neutrophilia. Neutrophilia was not associated with concurrent or adjuvant temodal discontinuation (p > 0.3). The 2-year actuarial overall survival was 45%. Steroid consumption, i.e. 60 mg or more of daily prednisolone, increased pretreatment neutrophil count (p = 0.005). In univariate analysis, neutrophilia was associated with worse overall survival (p = 0.019), as well as age ≥ 65 years (p = 0.009), surgical resection < 90% (p = 0.003) and prednisolone consumption ≥ 60 mg/day (p = 0.016). In multivariate analysis, neutrophilia (p = 0.013), age ≥ 65 (p = 0.001), and surgical tumor resection < 90% (p = 0.010) independently decreased overall survival, while, steroid consumption was not (p = 0.088)., Conclusion: In high-grade gliomas treated with concurrent temozolomide and radiation, pretreatment neutrophilia may be a significant prognosis factor for overall survival. In addition with previously available markers, this independent cost-effective biomarker could help identifying patients with worsened prognosis.

Purpose: To analyse feasibility, prognostic factors and patterns of recurrence after concurrent reirradiation and bevacizumab for recurrent high-grade gliomas., Patients and Methods: Between 2009 and 2015, 35 patients (median 57-year-old; 21 men, 14 women) with WHO grade III (n=11) or grade IV (n=24) gliomas were included in this retrospective and consecutive single-centre study. All patients received bevacizumab (median number of treatments: 12) concomitant with reirradiation (median dose: 45Gy, median number of fractions: 18) for recurrence with median 22 months (range: 5.6-123.7 months) from first irradiation (median dose: 60Gy)., Results: The median follow-up was 9.2 months from reirradiation. The median overall survival from reirradiation was 10.5 months (95% confidence interval [95% CI]: 4.9-16.1) and the progression-free survival from reirradiation was 6.7 months (95% CI: 2.9-10.5). The median overall survival from initial diagnosis was 44.6 months (95% CI: 32-57.1). No grade 3 toxicity or above was reported. Prognostic factors significantly correlated with better overall survival in univariate analysis were: age at least 55 (P=0.024), initial surgery (P=0.003), and 2Gy equivalent dose (EQD2) at least 50Gy at reirradiation (P=0.046). Twenty-two patients bevacizumab-naïve at time of reirradiation had a significantly increased overall survival from reirradiation compared to patients treated with reirradiation after bevacizumab failure (17.7 vs. 5.4 months, P<0.001) as well as overall survival from initial diagnosis (58.9 vs. 33.5 months, P=0.006). This outcome was similar in patients with initial glioblastomas (P=0.018) or anaplastic gliomas (P=0.021). There was no correlation between overall survival and gross tumour volume or planning target volume, frontal localization, or number of salvage therapies before reirradiation (P>0.05)., Conclusions: Concomitant reirradiation with bevacizumab in high-grade recurrent gliomas shows encouraging results in terms of survival and toxicities. Our data suggest that reirradiation should be favoured at initiation of bevacizumab, with EQD2 at least 50Gy., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

For newly diagnosed glioblastomas treated with resection in association with the standard combined chemoradiotherapy, the impact of Carmustine wafer implantation remains debated regarding postoperative infections, quality of life, and feasibility of adjuvant oncological treatments. To assess together safety, tolerance and efficacy of Carmustine wafer implantation and of extent of resection for glioblastoma patients in real-life experience. Observational retrospective monocentric study including 340 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent surgical resection with (n = 123) or without (n = 217) Carmustine wafer implantation as first-line oncological treatment. Carmustine wafer implantation and extent of resection did not significantly increase postoperative complications, including postoperative infections (p = 0.269, and p = 0.446, respectively). Carmustine wafer implantation and extent of resection did not significantly increase adverse events during adjuvant oncological therapies (p = 0.968, and p = 0.571, respectively). Carmustine wafer implantation did not significantly alter the early postoperative Karnofsky performance status (p = 0.402) or the Karnofsky performance status after oncological treatment (p = 0.636) but a subtotal or total surgical resection significantly improved those scores (p < 0.001, and p < 0.001, respectively). Carmustine wafer implantation, subtotal and total resection, and standard combined chemoradiotherapy were independently associated with longer event-free survival (adjusted Hazard Ratio (aHR), 0.74 [95% CI 0.55-0.99], p = 0.043; aHR, 0.70 [95% CI 0.54-0.91], p = 0.009; aHR, 0.40 [95% CI 0.29-0.55], p < 0.001, respectively) and with longer overall survival (aHR, 0.69 [95% CI 0.49-0.96], p = 0.029; aHR, 0.52 [95% CI 0.38-0.70], p < 0.001; aHR, 0.58 [95% CI 0.42-0.81], p = 0.002, respectively). Carmustine wafer implantation in combination with maximal resection, followed by standard combined chemoradiotherapy is safe, efficient, and well-tolerated in newly diagnosed supratentorial glioblastomas in adults.