Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects.

Improving the tumor reoxygenation to sensitize the tumor to radiation therapy is a cornerstone in radiation oncology. Here, the pre-clinical development of a clinically transferable liposomal formulation encapsulating trans sodium crocetinate (NP TSC) is reported to improve oxygen diffusion through the tumor environment. Early pharmacokinetic analysis of the clinical trial of this molecule performed on 37 patients orient to define the optimal fixed dosage to use in a triple-negative breast cancer model to validate the therapeutic combination of radiation therapy and NP TSC. Notably, it is reported that this formulation is non-toxic in both humans and mice at the defined fixed concentration, provides a normalization of the tumor vasculature within 72 h window after systemic injection, leads to a transient increase (50% improvement) in the tumor oxygenation, and significantly improves the efficacy of both mono-fractionated and fractionated radiation therapy treatment. Together, these findings support the introduction of a first-in-class therapeutic construct capable of tumor-specific reoxygenation without associated toxicities.

Post-operative flank irradiation using conformal versus highly conformal radiotherapy techniques for paediatric renal tumours: Results from the French registry PediaRT.

PURPOSE: Three-dimensional conformal RT (3D-RT) techniques are gold standard for post-operative flank radiotherapy (RT) in paediatric renal tumours. Recently, highly conformal RT (HC-RT) techniques have been implemented without comparative clinical data. The main objective of this multicentre study was to compare locoregional control (LRC) in children treated either with HC-RT or 3D-RT techniques. METHODS: Patients treated with post-operative flank RT for renal tumour registered in the national cohort PediaRT between March 2013 and September 2019 were included. Treatment and follow-up data, including toxicities and outcomes, were retrieved from the database. LRC was calculated, and dose reconstruction was performed in case of an event. RESULTS: Seventy-nine patients were included. Forty patients were treated with HC-RT and 39 with 3D-RT. Median follow-up was 4.5 years. Three patients had locoregional failure (LRF; 4%). HC-RT was not associated with a higher risk of LRF. Three-year LRC were 97.4% and 94.7% in the HC-RT and 3D-RT groups, respectively. The proportion of planning target volumes receiving 95% or more of the prescribed dose did not significantly differ between both groups (HC-RT 88%; 3D-RT 69%; p = .05). HC-RT was better achieving dose constraints, and a significant mean dose reduction was observed in the peritoneal cavity and pancreas associated with lower incidence of acute gastrointestinal toxicity. CONCLUSION: LRF after post-operative flank RT for renal tumours was rare and did not increase using HC-RT versus 3D-RT techniques. Dose to the pancreas and the peritoneal cavity, as well as acute toxicity, were reduced with HC-RT compared to 3D-RT.

Predictive value of health-related quality of life on radiotherapy-related toxicities in patients with head and neck cancer.

PURPOSE: Little is known about whether baseline health-related quality of life (HRQoL) scores also could predict occurrence radiotherapy-related toxicities, which we aim to assess in this study. METHODS: This study analyzed data from 200 patients enrolled in randomized study investigating the utility of HRQoL. HRQOL was assessed at baseline and during follow up using QLQ-C30 questionnaire and major toxicity was considered as adverse event ≥ 3 according to NCI-CTCAE classification. Cox regressions adjusting for clinical and sociodemographic data were used to assess prognostic significance of HRQOL scores. RESULTS: In multivariable analyses adjusted on clinical and sociodemographic data, every 10-point improvement in physical (HR = 0.74), role (HR = 0.87) and social (HR = 0.88) functioning was associated with 24%, 13% and 12% lower hazard of occurrence of major toxicity respectively while every 10 point-increase in dyspnea (HR = and loss appetite was associated with 15% and 16% increased hazard of major toxicity. CONCLUSION: Certain baseline HRQoL scores were found to be significantly associated with the occurrence of major toxicity.

An Explainable MRI-Radiomic Quantum Neural Network to Differentiate Between Large Brain Metastases and High-Grade Glioma Using Quantum Annealing for Feature Selection.

Solitary large brain metastases (LBM) and high-grade gliomas (HGG) are sometimes hard to differentiate on MRI. The management differs significantly between these two entities, and non-invasive methods that help differentiate between them are eagerly needed to avoid potentially morbid biopsies and surgical procedures. We explore herein the performance and interpretability of an MRI-radiomics variational quantum neural network (QNN) using a quantum-annealing mutual-information (MI) feature selection approach. We retrospectively included 423 patients with HGG and LBM (> 2 cm) who had a contrast-enhanced T1-weighted (CE-T1) MRI between 2012 and 2019. After exclusion, 72 HGG and 129 LBM were kept. Tumors were manually segmented, and a 5-mm peri-tumoral ring was created. MRI images were pre-processed, and 1813 radiomic features were extracted. A set of best features based on MI was selected. MI and conditional-MI were embedded into a quadratic unconstrained binary optimization (QUBO) formulation that was mapped to an Ising-model and submitted to D'Wave's quantum annealer to solve for the best combination of 10 features. The 10 selected features were embedded into a 2-qubits QNN using PennyLane library. The model was evaluated for balanced-accuracy (bACC) and area under the receiver operating characteristic curve (ROC-AUC) on the test set. The model performance was benchmarked against two classical models: dense neural networks (DNN) and extreme gradient boosting (XGB). Shapley values were calculated to interpret sample-wise predictions on the test set. The best 10-feature combination included 6 tumor and 4 ring features. For QNN, DNN, and XGB, respectively, training ROC-AUC was 0.86, 0.95, and 0.94; test ROC-AUC was 0.76, 0.75, and 0.79; and test bACC was 0.74, 0.73, and 0.72. The two most influential features were tumor Laplacian-of-Gaussian-GLRLM-Entropy and sphericity. We developed an accurate interpretable QNN model with quantum-informed feature selection to differentiate between LBM and HGG on CE-T1 brain MRI. The model performance is comparable to state-of-the-art classical models.

Quality control of 3D MRSI data in glioblastoma: Can we do without the experts?

PURPOSE: Proton magnetic resonance spectroscopic imaging (1H MRSI) is a noninvasive technique for assessing tumor metabolism. Manual inspection is still the gold standard for quality control (QC) of spectra, but it is both time-consuming and subjective. The aim of the present study was to assess automatic QC of glioblastoma MRSI data using random forest analysis. METHODS: Data for 25 patients, acquired prospectively in a preradiotherapy examination, were submitted to postprocessing with syngo.MR Spectro (VB40A; Siemens) or Java-based magnetic resonance user interface (jMRUI) software. A total of 28 features were extracted from each spectrum for the automatic QC. Three spectroscopists also performed manual inspections, labeling each spectrum as good or poor quality. All statistical analyses, with addressing unbalanced data, were conducted with R 3.6.1 (R Foundation for Statistical Computing; https://www.r-project.org). RESULTS: The random forest method classified the spectra with an area under the curve of 95.5%, sensitivity of 95.8%, and specificity of 81.7%. The most important feature for the classification was Residuum_Lipids_Versus_Fit, obtained with syngo.MR Spectro. CONCLUSION: The automatic QC method was able to distinguish between good- and poor-quality spectra, and can be used by radiation oncologists who are not spectroscopy experts. This study revealed a novel set of MRSI signal features that are closely correlated with spectral quality.

Local recurrence and cerebral progression-free survival after multiple sessions of stereotactic radiotherapy of brain metastases: a retrospective study of 184 patients : Statistical analysis.

PURPOSE: Forty to sixty percent of patients treated with focal therapy for brain metastasis (BM) will have distant brain recurrence (C-LR), while 10-25% of patients will have local recurrence (LR) within 1 year after stereotactic radiotherapy (SRT). The purpose of this study was to analyze cerebral progression-free survival (C-PFS) and LR of BM among patients treated with repeated courses of radiotherapy in stereotactic conditions. METHODS AND MATERIALS: We retrospectively reviewed data from 184 patients treated for 915 BMs with at least two courses of SRT without previous WBRT. Initial patient characteristics, patient characteristics at each SRT, brain metastasis velocity (BMV), delay between SRT, MRI response, LR and C­LR were analyzed. RESULTS: In all, 123 (66.9%), 39 (21.2%), and 22 (12%) patients received 2, 3, or 4 or more SRT sessions, respectively. Ninety percent of BMs were irradiated without prior surgery, and 10% were irradiated after neurosurgery. The MRI response at 3, 6, 12 and 24 months after SRT was stable regardless of the SRT session. At 6, 12 and 24 months, the rates of local control were 96.3, 90.1, and 85.8%, respectively. In multivariate analysis, P­LR was statistically associated with kidney (HR = 0.08) and lung cancer (HR = 0.3), ECOG 1 (HR = 0.5), and high BMV grade (HR = 5.6). The median C­PFS after SRT1, SRT2, SRT3 and SRT4 and more were 6.6, 5.1, 6.7, and 7.7 months, respectively. C­PFS after SRT2 was significantly longer among patients in good general condition (HR = 0.39), patients with high KPS (HR = 0.91), patients with no extracerebral progression (HR = 1.8), and patients with a low BMV grade (low vs. high: HR = 3.8). CONCLUSION: Objective MRI response rate after repeated SRT is stable from session to session. Patients who survive longer, such as patients with breast cancer or with low BMV grade, are at risk of local reirradiation. C­PFS after SRT2 is better in patients in good general condition, without extracerebral progression and with low BMV grade.

Immune-related aseptic meningitis and strategies to manage immune checkpoint inhibitor therapy: a systematic review.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) can induce adverse neurological effects. Due to its rarity as an adverse effect, meningitis has been poorly described. Therefore, meningitis diagnosis and management can be challenging for specialists. Moreover, meningitis can be an obstacle to resuming immunotherapy. Given the lack of alternatives, the possibility of reintroducing immunotherapy should be discussed on an individual basis. Here, we present a comprehensive systematic review of meningitis related to ICIs. REVIEW: We performed a search for articles regarding immune-related meningitis published in PubMed up to November 2021 with the MeSH terms "meningitis" and "immune checkpoint" using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We summarized the studies not only by category but also based on whether it was a primary article or case report to provide a systematic overview of the subject. We reviewed a total of 38 studies and herein report the clinical experiences, pharmacovigilance data and group knowledge from these studies. CONCLUSION: This review summarizes the existing information on immune-related meningitis and the possibility of reintroducing immunotherapy after the development of central neurological side effects. To the best of our knowledge, there is little information in the literature to guide clinicians on decisions regarding whether immunotherapy should be continued after a neurological adverse event occurs, especially meningeal events. This review emphasizes the necessity of systematic examinations, steroid treatment (as a cornerstone of management) and the need for further exploratory studies to obtain a clearer understanding of how to better manage patients who experience these side effects. The findings summarized in this review can help provide guidance to practitioners who face this clinical situation.

Does interventional MRI-guided brain cryotherapy cause a blood-brain barrier disruption? Radiological analysis and perspectives.

Glioblastoma is the most common primary malignant brain tumor with an incidence of 5/100,000 inhabitants/year and a 5-year survival rate of 6.8%. Despite recent advances in the molecular biology understanding of glioblastoma, CNS chemotherapy remains challenging because of the impermeable blood-brain barrier (BBB). Interventional MRI-guided brain cryotherapy (IMRgC) is technique that creates a tissue lesion by making a severe targeted hypothermia and possibly a BBB disruption. This study goal was to analyze the effect of IMRgC on human BBB glioblastoma through its gadolinium enhancing features. All patients harboring a local glioblastoma recurrence and meeting all the inclusion criteria were consecutively included into this retrospective study during a 2-year period. The primary endpoint was to analyze the modification of the gadolinium enhancement on MRI T1 sequences using MR perfusion weighted images during follow-up. The secondary endpoint was to assess any ischemic/hemorrhagic complication following cryotherapy procedure using diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), or fluid-attenuated inversion recovery (FLAIR). Among the 6 patients studied, all (100%) showed a BBB disruption on the cryotherapy site through the analysis of the perfusion weighted images with an average delay of 2.83 months following the procedure. The gadolinium enhancement located around the cavity then spontaneously decreased in 4/6 patients (67%). No ischemic or hemorrhagic complication was recorded. This study confirms the IMRgC capacity to disrupt BBB as already suggested by the literature. IMRgC might represent a new option in the management of GBM allowing the combined effect of direct cryoablation and enhanced chemotherapy.

Incidental axillary dose delivery to axillary lymph node levels I-III by different techniques of whole-breast irradiation: a systematic literature review.

BACKGROUND AND OBJECTIVE: In breast cancer treatment, radiotherapy is an essential component for locoregional management. Axillary recurrence in patients with invasive breast carcinoma remains an issue. The question of whether breast irradiation may unintentionally include levels I, II, and III, and may decrease the risk of axillary recurrence, remains a topic of discussion. PATIENTS AND METHODS: A literature search was performed in PubMed and the Cochrane Library to identify articles that have published data regarding dose-volume analysis of axillary levels in breast irradiation. The following MESH terms were used: "breast cancer/lymph nodes" AND "radiotherapy dosage." RESULTS: Thirteen articles were identified. The irradiation technique, initial dose prescribed to the breast, delineated volumes, and dose received at axillary levels were heterogeneous. The average dose delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using standard fields (ST) ranged between 22 and 43.5 Gy, 3 and 35.6 Gy, and 1.0 and 20.5 Gy, respectively. The average doses delivered to axilla levels I, II, and III with three-dimensional conformal radiotherapy using "high tangential" fields (HT) ranged between 38 and 49.7 Gy, 11 and 47.1 Gy, and 5 and 44.7 Gy, respectively. Finally, the average doses delivered to axilla levels I, II, and III using intensity-modulated radiation therapy (IMRT) were between 14.5 and 42.6 Gy, 3.4 and 35 Gy, and 1.2 and 25.5 Gy, respectively. CONCLUSION: Our literature review suggests that the incidental dose delivered to the axilla during whole-breast irradiation is heterogenous and dependent on the irradiation technique used. However, whether this observation can be translated into a therapeutic effect is still a matter of debate.

Gemcitabine-Based Chemoradiotherapy Enhanced by a PARP Inhibitor in Pancreatic Cancer Cell Lines.

Pancreatic ductal adenocarcinoma is a devastating disease with a 5-year overall survival of 9% for all stages. Gemcitabine-based chemoradiotherapy for locally advanced pancreatic cancer is highly toxic. We conducted an in vitro study to determine whether poly(ADP-ribose) polymerase-1 inhibition radiosensitized gemcitabine-based chemotherapy. Human pancreatic cancer cell lines, MIA PaCa-2, AsPC-1, BxPC-3 and PANC-1 were treated with gemcitabine (10 nM) and/or olaparib (1 µM). Low-LET gamma single dose of 2, 5 and 10 Gy radiations were carried out. Clonogenic assay, PAR immunoblotting, cell cycle distribution, γH2Ax, necrotic and autophagic cell death quantifications were performed. Treatment with olaparib alone was not cytotoxic, but highly radiosensitized cell lines, particularly at high dose per fraction A non-cytotoxic concentration of gemcitabine radiosensitized cells, but less than olaparib. Interestingly, olaparib significantly enhanced gemcitabine-based radiosensitization in PDAC cell lines with synergistic effect in BxPC-3 cell line. All cell lines were radiosensitized by the combination of gemcitabine and olaparib, through an increase of unrepaired double-strand, a G2 phase block and cell death. Radiosensitization was increased with high dose of radiation. The combination of olaparib with gemcitabine-based chemoradiotherapy could lead to an enhancement of local control in vivo and an improvement in disease-free survival.

Should the management of radiation therapy for breast cancer be standardized? Results of a survey on current French practices in breast radiotherapy.

BACKGROUND: Breast cancer is the most frequent cancer in women in France. Its management has evolved considerably in recent years with a focus on reducing iatrogenic toxicity. The radiotherapy indications are validated in multidisciplinary consultation meetings; however, questions remain outstanding, particularly regarding hypofractionated radiotherapy, partial breast irradiation, and irradiation of the internal mammary chain and axillary lymph node area. MATERIALS AND METHODS: An online survey was sent to 47 heads of radiotherapy departments in France. The survey consisted of 22 questions concerning indications for irradiation of the supraclavicular, internal mammary and axillary lymph node areas; irradiation techniques and modalities; prescribed doses; and fractionation. RESULTS: Twenty-four out of 47 centers responded (response rate of 51%). This survey demonstrated a wide variation in the prescribed dose regimen, monoisocentric radiotherapy, and indications of irradiation of the lymph node areas. CONCLUSION: This survey provides insight into the current radiotherapy practice for breast cancer in France. It shows the need to standardize practices.

Internal mammary and medial supraclavicular lymph node chain irradiation in stage I-III breast cancer (EORTC 22922/10925): 15-year results of a randomised, phase 3 trial.

BACKGROUND: 10-year results from several studies showed improved disease-free survival and distant metastasis-free survival, reduced breast cancer-related mortality, and variable effects on overall survival with the addition of partial or comprehensive regional lymph node irradiation after surgery in patients with breast cancer. We present the scheduled 15-year analysis of the European Organisation for Research and Treatment of Cancer (EORTC) 22922/10925 trial, which aims to investigate the impact on overall survival of elective internal mammary and medial supraclavicular (IM-MS) irradiation. METHODS: EORTC 22922/10925, a randomised, phase 3 trial done across 46 radiation oncology departments from 13 countries, included women up to 75 years of age with unilateral, histologically confirmed, stage I-III breast adenocarcinoma with involved axillary nodes or a central or medially located primary tumour. Surgery consisted of mastectomy or breast-conserving surgery and axillary staging. Patients were randomly assigned (1:1) centrally using minimisation to receive IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group). Stratification was done for institution, menopausal status, site of the primary tumour within the breast, type of breast and axillary surgery, and pathological T and N stage. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival analysed according to the intention-to-treat principle. Secondary endpoints were disease-free survival, distant metastasis-free survival, breast cancer mortality, any breast cancer recurrence, and cause of death. Follow-up is ongoing for 20 years after randomisation. This study is registered with ClinicalTrials.gov, NCT00002851. FINDINGS: Between Aug 5, 1996, and Jan 13, 2004, we enrolled 4004 patients, of whom 2002 were randomly assigned to the IM-MS irradiation group and 2002 to the no IM-MS irradiation group. At a median follow-up of 15·7 years (IQR 14·0-17·6), 554 (27·7%) patients in the IM-MS irradiation group and 569 (28·4%) patients in the control group had died. Overall survival was 73·1% (95% CI 71·0-75·2) in the IM-MS irradiation group and 70·9% (68·6-72·9) in the control group (HR 0·95 [95% CI 0·84-1·06], p=0·36). Any breast cancer recurrence (24·5% [95% CI 22·5-26·6] vs 27·1% [25·1-29·2]; HR 0·87 [95% CI 0·77-0·98], p=0·024) and breast cancer mortality (16·0% [14·3-17·7] vs 19·8% [18·0-21·7]; 0·81 [0·70-0·94], p=0·0055) were lower in the IM-MS irradiation group than in the control group. No significant differences in the IM-MS irradiation group versus the control group were seen for disease-free survival (60·8% [95% CI 58·4-63·2] vs 59·9% [57·5-62·2]; HR 0·93 [95% CI 0·84-1·03], p=0·18), or distant metastasis-free survival (70·0% [67·7-72·2] vs 68·2% [65·9-70·3]; 0·93 [0·83-1·04], p=0·18). Causes of death between groups were similar. INTERPRETATION: The 15-year results show a significant reduction of breast cancer mortality and any breast cancer recurrence by IM-MS irradiation in stage I-III breast cancer. However, this is not converted to improved overall survival. FUNDING: US National Cancer Institute, Ligue Nationale contre le Cancer, and KWF Kankerbestrijding.

Sensitivity of the Montreal Cognitive Assessment in screening for cognitive impairment in patients with newly diagnosed high-grade glioma.

INTRODUCTION: Cognitive impairment is frequent in patients with high-grade glioma and requires cognitive follow-up. Cognitive screening tools such as the Montreal Cognitive Assessment (MoCA) have been used to assess cognition in these patients. Here we assessed the sensitivity of the MoCA in screening for cognitive impairment in a cohort of 156 patients with newly-diagnosed high-grade glioma, after surgery and before radiochemotherapy. METHODS: We assessed cognitive performance with the MoCA and a neuropsychological battery. Cognitive scores were analyzed in terms of a previously validated framework designed to control false positives and data for 1003 control participants from the GRECOGVASC study. After comparison of performance on the tests, we used stepwise logistic regression to produce a cognitive summary score from the neuropsychological battery. Then we analyzed sensitivity and specificity of the MoCA with receiver operator characteristic (ROC) curve analysis. RESULTS: Both raw and adjusted MoCA scores showed only moderate sensitivity. The area under the ROC curve was 0.759 (95% CI 0.703-0.815) for the raw score and 0.788 (95% CI 0.734-0.842) for the adjusted score. Optimal discrimination was obtained with a raw score ≤ 25 (sensitivity: 0.526; specificity: 0.832; positive predictive value: 0.2; negative predictive value: 0.96) and an adjusted score - 0.603 (sensitivity: 0.716; specificity: 0.768; positive predictive value: 0.24; negative predictive value: 0.96). CONCLUSION: The moderate sensitivity of MoCA indicates that it is not a suitable screening tool for detecting cognitive impairment in patients with newly-diagnosed high-grade glioma.

An integrated genomic and metabolomic approach for defining survival time in adult oligodendrogliomas patients.

INTRODUCTION: The identification of frequent acquired mutations shows that patients with oligodendrogliomas have divergent biology with differing prognoses regardless of histological classification. A better understanding of molecular features as well as their metabolic pathways is essential. OBJECTIVES: The aim of this study was to examine the relationship between the tumor metabolome, six genomic aberrations (isocitrate dehydrogenase1 [IDH1] mutation, 1p/19q codeletion, tumor protein p53 [TP53] mutation, O6-methylguanin-DNA methyltransferase [MGMT] promoter methylation, epidermal growth factor receptor [EGFR] amplification, phosphate and tensin homolog [PTEN] methylation), and the patients' survival time. METHODS: We applied 1H high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy to 72 resected oligodendrogliomas. RESULTS: The presence of IDH1, TP53, 1p19q codeletion, MGMT promoter methylation reduced the relative risk of death, whereas PTEN methylation and EGFR amplification were associated with poor prognosis. Increased concentration of 2-hydroxyglutarate (2HG), N-acetyl-aspartate (NAA), myo-inositol and the glycerophosphocholine/phosphocholine (GPC/PC) ratio were good prognostic factors. Increasing the concentration of serine, glycine, glutamate and alanine led to an increased relative risk of death. CONCLUSION: HRMAS NMR spectroscopy provides accurate information on the metabolomics of oligodendrogliomas, making it possible to find new biomarkers indicative of survival. It enables rapid characterization of intact tissue and could be used as an intraoperative method.

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.

BACKGROUND: Glioblastoma, a high-grade glial infiltrating tumor, is the most frequent malignant brain tumor in adults and carries a dismal prognosis. External beam radiotherapy (EBRT) increases overall survival but this is still low due to local relapses, mostly occurring in the irradiation field. As the ratio of spectra of choline/N acetyl aspartate> 2 (CNR2) on MR spectroscopic imaging has been described as predictive for the site of local relapse, we hypothesized that dose escalation on these regions would increase local control and hence global survival. 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.

Grade III meningioma with gastro-intestinal tract and brain metastases: case report and review of the literature.

BACKGROUND: Meningioma is the most common adult primary intracranial tumor. Malignant meningioma is a rare variant of meningioma. The prognosis for the patients with these tumors is poor, due to the tumor's capacity for relapse and to develop distant metastases. These tumors can present the same evolutionary course as aggressive carcinoma. CASE DESCRIPTION: We report the case of distant brain and gastro-intestinal tract (GIT) metastases. A 78-year-old patient developed malignant meningioma with a Ki-67 proliferative index of 40%. According to guidelines, surgery followed by postoperative radiotherapy (RT) was performed. Three months after the end of RT, he presented histologically proven meningioma distant brain and GIT metastases. CONCLUSIONS: To our knowledge, this is the first case of meningioma GIT metastases. Also, we report the difficulty to confirm the diagnosis of meningioma metastases. Indeed, malignant meningioma has the same histopathological features as melanoma or carcinoma. The standard of care for the management of malignant meningioma is gross total surgery followed by postoperative radiotherapy. Metastatic meningioma is uncommon and no guidelines for the management of recurrent or metastatic meningioma have yet been published. However, several studies reported systemic therapeutic options such as antibody against VEGF, somatostatin analogs, PDGF-R, and VEGF-R tyrosine kinase inhibitors, in the case of recurrent or metastatic meningioma. We also made a review of the actual literature of systemic treatment options for metastatic meningioma.

Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model.

We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p < 0.001), while independent predictors of longer overall survival from progression included surgical resection (aHR, 0.57; 95% CI [0.44-0.73]; p < 0.001) and chemotherapy (aHR, 0.41; 95% CI [0.31-0.55]; p < 0.001). Single-tree recursive partitioning identified KPS at progression, surgical resection at progression, chemotherapy at progression, and RTOG-RPA class at histopathological diagnosis, as main survival predictors in the training set, yielding four risk categories highly predictive of overall survival from progression both in training (p < 0.0001) and validation (p < 0.0001) sets. Both random forest approaches identified KPS at progression as the most important survival predictor. Age, KPS at progression, RTOG-RPA classes, surgical resection at progression and chemotherapy at progression are prognostic for survival in recurrent glioblastomas and should inform the treatment decisions.

Surgery Is an Effective Option after Failure of Chemoradiation in Cancers of the Anal Canal and Anal Margin.

BACKGROUND: Surgery for anal canal cancer (ACC) and anal margin cancer (AMC) is the only curative option after failure of chemoradiotherapy (CRT). This study aimed to determine the efficacy of surgery for ACC or AMC after failed CRT. METHODS: This was a single-centre, retrospective study of 161 patients initially treated with CRT. We compared the survival rates of patients successfully treated by CRT with those of patients whose CRT failed (both surgically salvaged and treated palliatively). RESULTS: Thirty-one patients underwent surgery with curative intent, 20 received palliative treatment after failure of CRT, and 110 had effective CRT. The 5-year overall survival (OS) rate was significantly higher among patients with successful CRT than among patients who underwent surgery with curative intent (86 vs. 66%, p < 0.001). On the other hand, the 5-year OS of patients treated with curative surgery was significantly better than that of patients who underwent palliative treatment (66 vs. 13.5%, p < 0.001). The postoperative morbidity and mortality rates were 32 and 3%, respectively. Considering patients with failed CRT, curative surgery was the only factor prognostic of favourable OS in the multivariate analysis. CONCLUSION: Curative surgery after failure of CRT for ACC or AMC remains an effective treatment to improve survival in two-thirds of cases, resulting in high but manageable morbidity.

Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment?

A growing literature supports maximal safe resection followed by standard combined chemoradiotherapy (i.e. maximal first-line therapy) for selected elderly glioblastoma patients. To assess the prognostic factors from recurrence in elderly glioblastoma patients treated by maximal safe resection followed by standard combined chemoradiotherapy as first-line therapy. Multicentric retrospective analysis comparing the prognosis and optimal oncological management of recurrent glioblastomas between 660 adult patients aged of < 70 years (standard group) and 117 patients aged of ≥70 years (elderly group) harboring a supratentorial glioblastoma treated by maximal first-line therapy. From recurrence, both groups did not significantly differ regarding Karnofsky performance status (KPS) (p = 0.482). Oncological treatments from recurrence significantly differed: patients of the elderly group received less frequently oncological treatment from recurrence (p < 0.001), including surgical resection (p < 0.001), Bevacizumab therapy (p < 0.001), and second line chemotherapy other than Temozolomide (p < 0.001). In multivariate analysis, Age ≥70 years was not an independent predictor of overall survival from recurrence (p = 0.602), RTOG-RPA classes 5-6 (p = 0.050) and KPS at recurrence <70 (p < 0.001), available in all cases, were independent significant predictors of shorter overall survival from recurrence. Initial removal of ≥ 90% of enhancing tumor (p = 0.004), initial completion of the standard combined chemoradiotherapy (p = 0.007), oncological treatment from recurrence (p < 0.001), and particularly surgical resection (p < 0.001), Temozolomide (p = 0.046), and Bevacizumab therapy (p = 0.041) were all significant independent predictors of longer overall survival from recurrence. Elderly patients had substandard care from recurrence whereas age did not impact overall survival from recurrence contrary to KPS at recurrence <70. Treatment options from recurrence should include repeat surgery, second line chemotherapy and anti-angiogenic agents.