283 results on '"O. Chinot"'
Search Results
52. Technical evaluation of thymidine kinase assay in cytosols from breast cancers. EORTC Receptor Study Group Report
- Author
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S, Romain, F, Spyratos, O, Guirou, S, Deytieux, O, Chinot, and P M, Martin
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Observer Variation ,Cytosol ,Histocytological Preparation Techniques ,Prohibitins ,Humans ,Reproducibility of Results ,Breast Neoplasms ,Female ,Tissue Preservation ,Thymidine Kinase - Abstract
Pilot retrospective studies have pointed to the prognostic value of thymidine kinase (TK) in breast cancer. We studied the Prolifigen TK-REA assay (Sangtec Medical, Sweden), usually applied to serum, for TK analysis in breast cancer cytosols. Reproducibility was good, provided that small volume pipetting was performed carefully. The TK assay was not influenced by the short-term storage of cytosols in liquid nitrogen or at -80 degrees C. However, some steps appeared critical for good laboratory practice. The TK level was affected by thawing the cytosols more than twice. Tumour storage in liquid nitrogen should be preferred over storage at -80 degrees C. The components of the homogenisation buffer, especially sodium molybdate and KCl can have a marked influence on results. Finally, linearity problems arose with some cytosols. Thus, although assay of TK in cytosols is apparently simple, care must be taken in practice. The TK-REA kit should be standardised before widespread use in breast cancer.
- Published
- 1994
53. Metastatic Potential of Prostatic Cancer: Importance of Stroma-Epithelial Cell Interactions
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P. M. Martin, O. Chinot, and S. Romain
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Oncology ,medicine.medical_specialty ,medicine.anatomical_structure ,Stroma ,business.industry ,Internal medicine ,medicine ,Cancer research ,Cancer ,medicine.disease ,business ,Epithelium - Published
- 1994
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54. Chimiotherapie et radiotherapie des gliomes : evolution des concepts
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O. Chinot
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Radiological and Ultrasound Technology ,Radiology, Nuclear Medicine and imaging - Published
- 2006
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55. Subject Index Vol. 66, Suppl. 1, 1996
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G. Pendl, A. Pasoli, Zheng-qing Hu, W.Y. Chung, K.A. Leber, L. Widén, C.M. Duma, X. Wu, L. Kihlström, G. Pencil, S. Kawamoto, C.B. Chasan, Y.J. Lim, K. Takakura, M. Rossato, T. Tsuzuki, K. Suzuki, A.A. Kemeny, O. Major, S. Takai, M. Hirato, A. Nieoullon, S. Nakayama, H. Oyama, J. Hirato, J.C. Flickinger, T. Sakaki, M.M.H. Teng, V.P. Collins, A.H. Morice, I. Lax, R. Nicoletti, J. Russell, H.K. Inoue, Y. Andou, T. Kawamata, M. Rigotti, A. Bricolo, B. Masotto, S. Fukuoka, Y. Sasaki, S. Goetsch, T.D. Nichols, Y. Seo, Y.L. Lee, H. Sato, T. Hardy, Gene H. Barnett, S. Nakamura, S. Tsunoda, W. Leem, R. Sartori, J.A. Fiedler, W.P. Gwan, N. Konishi, D.M.C. Forster, M. Vial, M. Söderman, T. Kobayashi, G. Marchini, S. Babighian, C. Lindquist, M. Dal Sasso, S. Stone-Elander, Y. Umebara, F. Severi, Bin-Jiang Wang, M. Izawa, Jia-Zhong Dai, W.Y. Guo, M. Habeck, S. Takahashi, A. Pasqualin, P. Ferraresi, Y. Kwon, M. Ide, G. Barone, L. Manera, D.E. Schwartz, Xing-Rong Chen, W.R. Hudgins, A. Posewitz, S.J. Goetsch, Y. Hiasa, A. Benati, J. Nakagawara, Y. Imahori, S.S. Vermeulen, Y. Ohmori, E. Yoshino, J.C. Peragut, O. Chinot, C. Ohye, G.M. Friehs, M. Hayashi, R. Foroni, L.D. Lunsford, J. Jakubowski, L.K. Kerkerian-Legoff, B. Karlsson, A. Hampshire, Y. Kida, J. Mogard, O. Levrier, H.C. Pan, T. Yamaki, H. Tung, E. Kato, J. Régis, J. Plombon, J.L. Barker, Liang-fu Zhou, Zi-wei Gao, Y. Aoki, H. Fujino, S. Eustacchio, G. Norén, P. Grimm, H. Kohga, A. Lizarraras, E. Piovan, P. Farnarier, L. Bonomi, S. Hagiwara, H.J. Landy, S. Matsubara, M. Rey, M. Jimbo, D. Kondziolka, J.C. Ganz, J. Nakamura, J.Y. Ting, A. Nicolato, T. Tanaka, R.F. Young, M. Tago, K. Kitz, L.W. Wang, C.Y. Chang, C.J. Whang, Li Pan, J. Peragut, A.M. Markoe, T. Shibazaki, H. Nagano, C. Scharfen, K. Suematsu, R. Aigner, E. Maurincomme, A. Terahara, Ren-He Dong, D. Porcheron, T. Hirai, M. Nakamura, M. Yamamoto, L. Walton, K. Nakagawa, S. Furuya, H. Kurita, Wei-ming Xu, S. Naruse, G.F. Fueger, T. Higuchi, W.C. Chu, Wei-min Xu, K. Ott, A. Zama, O. Schröttner, H. Hiyama, H. Inoue, S. Murayama, R. Marks, G.P. Urbani, S. Ueda, K. Tanohata, K. Ericson, D. Hodgens, K. Nakaya, M. Niwa, T. Mori, M.C. Wu, K. Arai, M. Gerosa, and M. Takanashi
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Index (economics) ,business.industry ,Medicine ,Surgery ,Subject (documents) ,Neurology (clinical) ,business ,Neuroscience ,Clinical psychology - Published
- 1996
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56. Effet de l’inhibition de l’adrénomédulline après greffe intra- cérébrale de cellules de glioblastome humain chez la souris NUDE balb-c
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O. Chinot, S. Fuentes, null L’Houafik, P. Metellus, and F. Grisoli
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Surgery ,Neurology (clinical) - Published
- 2004
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57. P14.73 Toxicity and outcomes of reduced-dose whole brain radiotherapy as consolidation treatment for patients with CNS lymphoma in real life setting
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Khê Hoang-Xuan, V Rolland, Michel Fabbro, Caroline Houillier, C Chabrot, P Agape, Carole Soussain, S Chebrek, Anna Schmitt, Ghandi Damaj, P Lesueur, D Stefan, O Chinot, and Loïc Feuvret
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Consolidation (soil) ,business.industry ,Whole brain radiotherapy ,medicine.disease ,Reduced dose ,Lymphoma ,Poster Presentations ,Internal medicine ,Toxicity ,medicine ,In real life ,Neurology (clinical) ,business - Abstract
BACKGROUND Optimal treatment strategy for newly diagnosed primary PCNSL remains controversial. The high risk of radio-induced late-delayed neurotoxicity in patients who achieve long-term disease control constrains the use of classical consolidation WBRT. So as to reduce side cognitive effects, Morris et al, reported a phase II study, to assess the efficacy and toxicity of consolidation reduced-dose (23.4Gy) WBRT (rdWBRT) for patients with complete response after high dose methotrexate based chemotherapy. The study reported a 2-year PFS rate for these patients of 77%, with no evidence of significant cognitive decline during the follow-up (FU) period. The aim of this retrospective study was to report toxicity and outcomes of rdWBRT, in patients < 60 years old with complete response (CR) after HD-MTX based chemotherapy, in real life setting, without selection bias. MATERIAL AND METHODS Patients were selected from the French LOC network database, a nationwide database centralizing since 2011 information from 28 different centers in France, representing the main centers involved in PCNSL management. Patients were retrospectively selected according to the following criteria: 1) Pathological diagnosis of diffuse large B cell PCNSL; 2) age>18 and 1.5 g/m2); 5) CR according to the IPCG criteria after first-line induction treatment. Patients should have received a rdWBRT (23.4Gy in 13 fractions of 1.8Gy). RESULTS Twenty seven patients, were included. The median FU from initial diagnosis was 28.5 months [9.6–50.7]. Median age was 50.2 years [25–60]. Median Karnofsky Performans Status (KPS) was 90% [40–100%]. Seventeen patients had a multi focal disease at diagnosis (meningeal involvement n=6, in ophthalmic involvement n=4). PFS rates were 85% IC95[76–100 %], 65% IC95 [45–85%] and 65% IC95 [45–85%] at 1, 2, and 3 years respectively. The OS rates were 100%, 90,5% IC95 [77–100%] and 85%IC95 [69–100%]. 8 patients relapsed, with a median time from radiotherapy to recurrence of 6.5months [2.4–17]. All recurrences were outside the initially involved site(s), and 62.5% of tumors recurred as multifocal disease. All patients received salvage treatment, including intensive chemotherapy with autologous stem cell transplantation in 4 cases. No acute grade III-IV toxicity related to rdWBRT was reported. Neuropsychological follow up was available for 14 patients with no cognitive impairment at last follow up. CONCLUSION This is the largest retrospective study evaluating outcomes of rdWBRT for PCNSL young patients with CR after HD-MTX chemotherapy. Real life setting data from this study are quite reassuring, and rdWBRT could be considered as an efficient and safe consolidation strategy in this population. We need a longer FU to confirm the absence of cognitive deterioration.
58. P11.11 Aggressive Meningiomas: In vitro study of the combination pasireotide-everolimus vs. octreotide everolimus
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O Chinot, Céline Defilles, H. Dufour, Thomas Graillon, D. Romano, Dominique Figarella-Branger, Anne Barlier, and Pierre-Hugues Roche
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Everolimus ,P11 Meningiomas ,business.industry ,Octreotide ,Pasireotide ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Text mining ,chemistry ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,In vitro study ,Neurology (clinical) ,business ,medicine.drug
59. OS1.7 Plasmatic differential scanning fluorimetry profiles discriminate glioma patients from healthy controls
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Philipp O. Tsvetkov, Rémi Eyraud, Dominique Figarella-Branger, E. Tabouret, Soazig Malesinski, O Chinot, T Peel, and François Devred
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Cancer Research ,Pathology ,medicine.medical_specialty ,Tumor size ,Karnofsky Performance Status ,business.industry ,Astrocytoma ,medicine.disease ,Oncology ,Glioma ,Oral Presentations ,Medicine ,Neurology (clinical) ,Oligodendroglioma ,business ,Edetate disodium - Abstract
BACKGROUND differential scanning fluorimetry (DSF) has been recently proposed to be used to perform high throughput biofluids profiling by following protein denaturation. Our objective was to discriminate patients with glioma from healthy controls using plasmatic DSF profiles. MATERIAL AND METHODS We included 78 glioma patients and 44 healthy controls. Plasmas were collected using EDTA tubes and analyzed in duplicate using nanoDSF Prometheus NT.Plex instrument (Nanotemper). The following DSF data were analyzed: protein fluorescence at 330 and 350 nm, first derivation of the ratio of fluorescence at 330 and 350 and the absorbance at 350 nm. Then we ran several machine learning algorithms to differentiate gliomas from healthy controls: Logistic Regression (LR), Support Vector Machine (SVM), Neural Networks (NN), Random Forest (RF) and Adaptive Boosting (AdaBoost). All these methods have been tested using a leave-one-out approach where each datum is used once as test while the other are used to train the automatic classifiers. RESULTS We included 78 patients with a median age of 57.8 years (range, 21.8 - 89.9). Thirteen patients (17%) presented with a 1p/19q codeleted IDH mutated oligodendroglioma, 12 patients (15%) with an IDH mutated astrocytoma and 53 patients (68%) with an IDH wild-type astrocytoma, including 26 patients with a recurrent grade IV IDH wild-type astrocytoma. DSF data were independent from classical prognostic factors or patient characteristics: age, Karnofsky Performans Status, IDH mutation status, 1p19q codeletion, grade, initial or recurrent setting, steroid doses, patient size and weight, tumor size and location. The different datasets of the DFS output were tested independently and in combination as input of the machine learning algorithms. Results were obtained using the tuned best parameters on 157 data. The best obtained accuracy was 95.54% with 2% of fake positives and 5% of fake negatives (algorithm: SVM). Others achieved ≥ 90% of correct classification: LR accuracy was 89.17%, NN accuracy was 92.99%, RF accuracy was 91.72% and Adaboost accuracy was 92.36%. CONCLUSION DSF profiles analyzed by machine learning algorithms could allow us to identify glioma patients from healthy controls with an accuracy of more than 95%. These results suggest that DSF of biofluid could be a useful and non-invasive tool to monitor glioma patients. Further investigations, including longitudinal profile analyses are ongoing.
60. High-dose chemotherapy with autologous haematopoietic stem cell transplantation in patients with isolated vitreoretinal lymphoma: a LOC network study.
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Mainguy A, Soussain C, Touitou V, Bennedjai A, Kodjikian L, Ghesquières H, Damaj G, Gressin R, Ducloyer JB, Chinot O, Vautier A, Moluçon-Chabrot C, Ahle G, Taillandier L, Marolleau JP, Chauchet A, Jardin F, Cassoux N, Malaise D, Toutée A, Touhami S, Le Garff-Tavernier M, Hoang-Xuan K, Choquet S, and Houillier C
- Abstract
Despite its indolent evolution, vitreoretinal lymphoma (VRL) has a poor prognosis due to a major risk of relapse in the central nervous system (CNS) and may necessitate aggressive therapy. However, the use of high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is poorly documented. We retrospectively analysed from the French LOC network database the adult immunocompetent patients treated with HCT-ASCT for isolated VRL. Thirty-eight patients underwent consolidation with HCT-ASCT for isolated VRL between 2008 and 2019 after induction chemotherapy. Twenty patients had primary VRL, and 18 had an isolated VRL relapse of a primary CNS lymphoma. Three patients underwent HCT-ASCT in first-line treatment, 24 in second-line treatment, and 11 in subsequent lines. At HCT-ASCT, the median age was 61 years, and the median KPS was 90. Thirty-two patients (84%) received high-dose thiotepa-based HCT. One patient (3%) died from HCT-ASCT toxicity. Nineteen (50%) patients relapsed after HCT-ASCT, including 17 cases occurring in the brain. The median progression-free survival, brain-free survival and overall survival from HCT-ASCT were 96, 113 and 92 months, respectively. HCT-ASCT represents an effective therapeutic strategy for select VRL patients, with a tolerable safety profile. However, the risk of subsequent brain relapse remains significant., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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61. Correction: Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients.
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Alcantara M, Chevrier M, Jardin F, Schmitt A, Houillier C, Oberic L, Chinot O, Morschhauser F, Peyrade F, Houot R, Hoang-Xuan K, Ghesquieres H, and Soussain C
- Published
- 2024
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62. Survival Outcomes Associated With First-Line Procarbazine, CCNU, and Vincristine or Temozolomide in Combination With Radiotherapy in IDH-Mutant 1p/19q-Codeleted Grade 3 Oligodendroglioma.
- Author
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Kacimi SEO, Dehais C, Feuvret L, Chinot O, Carpentier C, Bronnimann C, Vauleon E, Djelad A, Cohen-Jonathan Moyal E, Langlois O, Campone M, Ducloie M, Noel G, Cuzzubbo S, Taillandier L, Ramirez C, Younan N, Menei P, Dhermain F, Desenclos C, Ghiringhelli F, Bourg V, Ricard D, Faillot T, Appay R, Tabouret E, Nichelli L, Mathon B, Thomas A, Tran S, Bielle F, Alentorn A, Iorgulescu JB, Boëlle PY, Labreche K, Hoang-Xuan K, Sanson M, Idbaih A, Figarella-Branger D, Ducray F, and Touat M
- Abstract
Purpose: Patients with IDH-mutant 1p/19q-codeleted grade 3 oligodendroglioma (O3
IDHmt/Codel ) benefit from adding alkylating agent chemotherapy to radiotherapy (RT). However, the optimal chemotherapy regimen between procarbazine, 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine (PCV) and temozolomide (TMZ) remains unclear given the lack of randomized trial data comparing both regimens., Methods: The objective was to assess the overall survival (OS) and progression-free survival (PFS) associated with first-line PCV/RT versus TMZ/RT in patients newly diagnosed with O3IDHmt/Codel . We included patients with histologically proven O3IDHmt/Codel (according to WHO criteria) from the French national prospective cohort Prise en charge des OLigodendrogliomes Anaplasiques (POLA). All tumors underwent central pathological review. OS and PFS from surgery were estimated using the Kaplan-Meier method and Cox regression model., Results: 305 newly diagnosed patients with O3IDHmt/Codel treated with RT and chemotherapy between 2008 and 2022 were included, of which 67.9% of patients (n = 207) were treated with PCV/RT and 32.1% with TMZ/RT (n = 98). The median follow-up was 78.4 months (IQR, 44.3-102.7). The median OS was not reached (95% CI, Not reached [NR] to NR) in the PCV/RT group and was 140 months (95% CI, 110 to NR) in the TMZ/RT group (log-rank P = .0033). On univariable analysis, there was a significant difference in favor of PCV/RT in both 5-year (PCV/RT: 89%, 95% CI, 85 to 94; TMZ/RT: 75%, 95% CI, 66 to 84) and 10-year OS (PCV/RT: 72%, 95% CI, 61 to 85; TMZ/RT: 60%, 95% CI, 49 to 73), which was confirmed using the multivariable Cox model adjusted for age, type of surgery, gender, Eastern Cooperative Oncology Group performance status, and CDKN2A homozygous deletion (hazard ratio, 0.53 for PCV/RT, 95% CI, 0.30 to 0.92, P = .025)., Conclusion: In patients with newly diagnosed O3IDHmt/Codel from the POLA cohort, first-line PCV/RT was associated with better OS outcomes compared with TMZ/RT. Our data suggest that the improved safety profile associated with TMZ comes at the cost of inferior efficacy in this population. Further investigation using prospective randomized studies is warranted.- Published
- 2024
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63. Early Urinary Potassium Level Predicts High-dose Methotrexate Elimination Delay in Primary Central Nervous System Lymphoma.
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Harlay V, Bertucci A, Boucard C, Petrirena G, Campello C, Barrié M, Autran D, Chinot O, and Tabouret E
- Subjects
- Humans, Female, Male, Aged, Middle Aged, Prospective Studies, Antimetabolites, Antineoplastic therapeutic use, Antimetabolites, Antineoplastic administration & dosage, Adult, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Methotrexate administration & dosage, Methotrexate therapeutic use, Methotrexate urine, Central Nervous System Neoplasms urine, Central Nervous System Neoplasms drug therapy, Lymphoma drug therapy, Lymphoma urine, Potassium urine, Potassium blood
- Abstract
Background/aim: Treatment of primary central nervous system lymphoma (PCNSL) includes high dose methotrexate-based polychemotherapy (HD-MTX). This study aimed to identify early predictive factors of methotrexate (MTX) delayed elimination., Patients and Methods: We prospectively included all patients with newly-diagnosed PCNSL. Daily serum and urinary creatinine and ionogram were collected. We generated two independent cohorts: a training cohort (TC) and a confirmatory cohort (CC)., Results: We included for analysis 64 cures of HD-MTX (20 patients) in the TC and 59 cures (22 patients) in the CC. Median elimination time of MTX was 95 h and 96 h in the TC and CC, respectively. In multivariate analysis, older age (p=0.004), low Karnofsky Performance Status (p=0.036) and high urinary K
+ (p=0.001) were associated with delayed MTX elimination. An optimal cutoff for urinary K+ was defined. In the CC, we confirmed that high urinary K+ (p=0.004) remained associated with delayed MTX elimination., Conclusion: High urinary K+ may be predictive of delayed MTX elimination in primary central nervous system lymphoma. Its relevance as a decision-making factor needs to be validated in additional prospective studies., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)- Published
- 2024
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64. Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients.
- Author
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Alcantara M, Chevrier M, Jardin F, Schmitt A, Houillier C, Oberic L, Chinot O, Morschhauser F, Peyrade F, Houot R, Hoang-Xuan K, Ghesquieres H, and Soussain C
- Subjects
- Humans, Middle Aged, Male, Female, Aged, Adult, Vincristine administration & dosage, Vincristine therapeutic use, Vincristine adverse effects, Rituximab administration & dosage, Rituximab therapeutic use, Rituximab adverse effects, Methotrexate administration & dosage, Methotrexate therapeutic use, Prednisone administration & dosage, Prednisone therapeutic use, Prednisone adverse effects, Lymphoma drug therapy, Lenalidomide administration & dosage, Lenalidomide therapeutic use, Lenalidomide adverse effects, Adenine analogs & derivatives, Adenine administration & dosage, Piperidines administration & dosage, Piperidines therapeutic use, Piperidines adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Central Nervous System Neoplasms drug therapy, Pyrimidines administration & dosage, Pyrimidines therapeutic use, Pyrimidines adverse effects, Pyrazoles administration & dosage, Pyrazoles therapeutic use, Pyrazoles adverse effects
- Abstract
Background: Results of conventional induction chemotherapies in primary central nervous system lymphoma (PCNSL) need to be improved. Ibrutinib, a BTK inhibitor, and lenalidomide, an immunomodulatory drug, have shown promising results at relapse, supporting to further assess their individual use in combination with high-dose methotrexate-based chemotherapy., Methods: Patients with newly diagnosed PCNSL were randomized to receive four 28-day cycles of ibrutinib or lenalidomide in combination with R-MPV (rituximab, methotrexate, procarbazine, vincristine and prednisone) in a 3 + 3 design. Responders then received a consolidation with R-Cytarabine and an intensive chemotherapy with autologous stem cell transplantation. The objective of the phase IB study was to define the recommended phase II dose (RP2D) based on the dose-limiting toxicity (DLT) occurring during the first induction cycle., Results: Twenty-six patients (median age 52) were randomized. Four DLTs were observed: one grade 5 aspergillosis and pneumocystosis, one grade 4 catheter-related infection and two grade 3 increased alanine aminotransferase levels. RP2D of ibrutinib and lenalidomide were 560 mg daily (D3-14 and D17-28) and 15 mg daily (D1-21) respectively, in combination with R-MPV. In both arms, the most frequent grade ≥3 treatment-related adverse events were hepatic cytolysis, neutropenia and infections. One grade 4 Lyell's syndrome was reported at cycle 2 in the lenalidomide arm. After 4 induction cycles, the overall response rates were 76.9% and 83.3% in the lenalidomide and ibrutinib arm, respectively., Conclusion: Targeted induction therapies combining lenalidomide or ibrutinib with R-MPV are feasible for first-line PCNSL. The safety profile is consistent with the known safety profiles of R-MPV and both targeted therapies. The phase II part of the study is ongoing., Trial Registration: NCT04446962., (© 2024. The Author(s).)
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- 2024
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65. TARGET: A phase I/II open-label multicenter study to assess safety and efficacy of fexagratinib in patients with relapsed/refractory FGFR fusion-positive glioma.
- Author
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Picca A, Di Stefano AL, Savatovsky J, Ducray F, Chinot O, Moyal EC, Augereau P, Le Rhun E, Schmitt Y, Rousseaux N, Yepnang AMM, Estellat C, Charbonneau F, Letourneur Q, Branger DF, Meyronet D, Fardeau C, Mokhtari K, Bielle F, Iavarone A, and Sanson M
- Abstract
Background: Oncogenic FGFR-TACC fusions are present in 3-5% of high-grade gliomas (HGGs). Fexagratinib (AZD4547) is an oral FGFR1-3 inhibitor with preclinical activity in FGFR-TACC+ gliomas. We tested its safety and efficacy in patients with recurrent FGFR-TACC + HGGs., Patients and Methods: TARGET (NCT02824133) is a phase I/II open-label multicenter study that included adult patients with FGFR-TACC + HGGs relapsing after ≥1 line of standard chemoradiation. Patients received fexagratinib 80 mg bd on a continuous schedule until disease progression or unacceptable toxicity. The primary endpoint was the 6-month progression-free survival rate (PFS6)., Results: Twelve patients with recurrent IDH wildtype FGFR-TACC + HGGs (all FGFR3-TACC3+) were included in the efficacy cohort (male/female ratio = 1.4, median age = 61.5 years). Most patients (67%) were included at the first relapse. The PFS6 was 25% (95% confidence interval 5-57%), with a median PFS of 1.4 months. All patients without progression at 6 months ( n = 3) were treated at first recurrence (versus 56% of those in progression) and remained progression-free for 14-23 months. The best response was RANO partial response in 1 patient (8%), stable disease in 5 (42%), and progressive disease in 6 (50%). Median survival was 17.5 months from inclusion. Grade 3 toxicities included lymphopenia, hyperglycaemia, stomatitis, nail changes, and alanine aminotransferase increase ( n = 1 each). No grade 4-5 toxicities were seen. A 32-gene signature was associated with the benefit of FGFR inhibition in FGFR3-TACC3 + HGGs., Conclusions: Fexagratinib exhibited acceptable toxicity but limited efficacy in recurrent FGFR3-TACC3 + HGGs. Patients treated at first recurrence appeared more likely to benefit, yet additional evidence is required., Competing Interests: A.P. and M.S. declare having received travel support from Astra Zeneca. The other authors have declared no conflict of interest relevant to this paper., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
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- 2024
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66. Peptide radionuclide radiation therapy with Lutathera in multirecurrent nonanaplastic meningiomas: antitumoral activity study by growth rate analysis.
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Graillon T, Salgues B, Horowitz T, Padovani L, Appay R, Tabouret E, Guedj E, and Chinot O
- Subjects
- Humans, Retrospective Studies, Female, Male, Middle Aged, Aged, Adult, Magnetic Resonance Imaging, Follow-Up Studies, Peptides therapeutic use, Meningioma radiotherapy, Meningioma pathology, Meningioma diagnostic imaging, Meningeal Neoplasms radiotherapy, Meningeal Neoplasms pathology, Meningeal Neoplasms diagnostic imaging, Neoplasm Recurrence, Local radiotherapy
- Abstract
Purpose: Several retrospective studies and meta-analyses of Peptide Radionuclide Radiation Therapy in meningiomas suggest six-month progression-free survival improvement for WHO grade 1 and 2 meningiomas. In the present study, we aimed to evaluate the impact of such treatment on three-dimensional volume growth rate (3DVGR) in nonanaplastic meningiomas., Methods: The authors performed a retrospective study including eight patients treated with Lutathera®. Millimetric 3D T1-weighted with gadolinium enhancement magnetic resonance imaging sequences were requested for volume measurement. Then, tumor growth rate was classified following a previously described 3DVGR classification (Graillon et al.)., Results: Patients harbored seven WHO grade 2 meningiomas and one aggressive WHO grade 1. All patients, except one, underwent four treatment cycles. 3DVGR significantly decreased at 3, 6, and 12 months after treatment initiation analyzing each lesion separately. Mean and median 3DVGR from all patients were respectively at 29.5% and 44.5%/6 months before treatment initiation, then at 16.5% and 25%/6 months at three months post-treatment initiation, 9.5% and 4.5%/6 months after 6 months, as well as 9.5% and 10.5%/6 months after 12 months. At 3, 6, and 12 months after treatment initiation, 4/8, 6/7, and 5/6 patients were class 2 (stabilization or severe 3DVGR slowdown), respectively. No patient was class 1 at 6 and 12 months, suggesting a lack of drug response., Conclusion: In nonanaplastic meningiomas, Lutathera®'s antitumoral activity appeared delayed and more likely observed at six months, while no major response was observed under treatment. Moreover, its antitumoral activity persisted for 12-18 months following treatment initiation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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67. Primary central nervous system lymphoma with initial spinal cord involvement (PCNSL-SC) is a rare entity: 4 case reports and review of literature.
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Harlay V, Campello C, Bequet C, Petrirena G, Barrie M, Appay R, Arnoux I, Loosveld M, Testud B, Bertucci A, Tabouret E, and Chinot O
- Subjects
- Humans, Male, Middle Aged, Female, Aged, Spinal Cord pathology, Spinal Cord diagnostic imaging, Lymphoma diagnosis, Lymphoma complications, Lymphoma pathology, Adult, Magnetic Resonance Imaging, Central Nervous System Neoplasms diagnosis, Central Nervous System Neoplasms complications, Central Nervous System Neoplasms pathology, Spinal Cord Neoplasms diagnosis, Spinal Cord Neoplasms complications, Spinal Cord Neoplasms diagnostic imaging, Spinal Cord Neoplasms pathology
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- 2024
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68. Repeated blood-brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial.
- Author
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Carpentier A, Stupp R, Sonabend AM, Dufour H, Chinot O, Mathon B, Ducray F, Guyotat J, Baize N, Menei P, de Groot J, Weinberg JS, Liu BP, Guemas E, Desseaux C, Schmitt C, Bouchoux G, Canney M, and Idbaih A
- Subjects
- Humans, Carboplatin adverse effects, Ultrasonography, Biological Transport, Antineoplastic Combined Chemotherapy Protocols adverse effects, Blood-Brain Barrier pathology, Glioblastoma diagnostic imaging, Glioblastoma drug therapy
- Abstract
Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion. The primary objective of the Phase 1 was to evaluate the safety of escalating numbers of ultrasound emitters using a standard 3 + 3 dose escalation. The primary objective of the Phase 2 was to evaluate the efficacy of BBB opening using magnetic resonance imaging (MRI). The secondary objectives included safety and clinical efficacy. Thirty-three patients received a total of 90 monthly sonications with carboplatin administration and up to nine emitters activated without observed DLT. Grade 3 procedure-related adverse events consisted of pre syncope (n = 3), fatigue (n = 1), wound infection (n = 2), and pain at time of device connection (n = 7). BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival rate was 58% and median overall survival was 14.0 months from surgery., (© 2024. The Author(s).)
- Published
- 2024
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69. Prognostic value of Beta 2-Microglobulinin in cerebrospinal fluid in primary central nervous system lymphoma.
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Bertucci A, Boucard C, Harlay V, Appay R, Petrirena G, Barrié M, Chinot O, and Tabouret E
- Subjects
- Humans, Prognosis, Sensitivity and Specificity, Central Nervous System, Central Nervous System Neoplasms diagnosis, Lymphoma diagnosis
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests.
- Published
- 2024
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70. A Multicenter Randomized Bioequivalence Study of a Novel Ready-to-Use Temozolomide Oral Suspension vs. Temozolomide Capsules.
- Author
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Ducray F, Ramirez C, Robert M, Fontanilles M, Bronnimann C, Chinot O, Estrade F, Durando X, Cartalat S, Bastid J, Bienayme H, and Lemarchand C
- Abstract
Background: Temozolomide (TMZ) oral suspension (Ped-TMZ, KIZFIZO
® ) is being developed for the treatment of relapsed or refractory neuroblastoma, a rare cancer affecting infants and young children. The study assessed the safety and the bioequivalence of this novel pediatric formulation with existing TMZ oral capsules., Methods: In vitro dissolution profiles and the bioequivalence were evaluated following the European Medicines Agency "Guidelines on the investigation of Bioequivalence". The phase I, multicenter, randomized, open-label, crossover, single-dose bioequivalence study enrolled 36 adult patients with glioblastoma multiforme or lower-grade glioma. Each patient received 200 mg/m2 Ped-TMZ suspension and TMZ capsules (Temodal® ) on 2 consecutive days, with the order being randomly assigned. Fourteen blood samples were collected up to 10 h post-dosing. Bioequivalence was assessed by comparing the 90% confidence interval for the ratio of the geometric means of maximum TMZ plasma concentration (Cmax ) and the area under the curve (AUCt). Other endpoints included further pharmacokinetic parameters and safety., Results: Both formulations exhibited a fast in vitro dissolution profile with more than 85% of TMZ dissolved within 15 min. For the bioequivalence study, thirty patients completed the trial as per the protocol. The ratio of Ped-TMZ/TMZ capsule geometric means (90% CI) for AUCt and Cmax were 97.18% (95.05-99.35%) and 107.62% (98.07-118.09%), respectively, i.e., within the 80-125% bioequivalence limits. No buccal toxicity was associated with Ped-TMZ liquid formulation., Conclusions: This study showed that Ped-TMZ oral suspension and TMZ oral capsule treatment are immediate release and bioequivalent medicines. There were also no unexpected safety signals or local toxicity (funded by ORPHELIA Pharma; ClinicalTrials.gov number, NCT04467346).- Published
- 2023
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71. Combination drug screen targeting glioblastoma core vulnerabilities reveals pharmacological synergisms.
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Ariey-Bonnet J, Berges R, Montero MP, Mouysset B, Piris P, Muller K, Pinna G, Failes TW, Arndt GM, Morando P, Baeza-Kallee N, Colin C, Chinot O, Braguer D, Morelli X, André N, Carré M, Tabouret E, Figarella-Branger D, Le Grand M, and Pasquier E
- Subjects
- Animals, Mice, Aurora Kinase A, Drug Synergism, Cell Line, Tumor, Drug Combinations, Glioblastoma drug therapy, Glioblastoma genetics, Antineoplastic Agents pharmacology
- Abstract
Background: Pharmacological synergisms are an attractive anticancer strategy. However, with more than 5000 approved-drugs and compounds in clinical development, identifying synergistic treatments represents a major challenge., Methods: High-throughput screening was combined with target deconvolution and functional genomics to reveal targetable vulnerabilities in glioblastoma. The role of the top gene hit was investigated by RNA interference, transcriptomics and immunohistochemistry in glioblastoma patient samples. Drug combination screen using a custom-made library of 88 compounds in association with six inhibitors of the identified glioblastoma vulnerabilities was performed to unveil pharmacological synergisms. Glioblastoma 3D spheroid, organotypic ex vivo and syngeneic orthotopic mouse models were used to validate synergistic treatments., Findings: Nine targetable vulnerabilities were identified in glioblastoma and the top gene hit RRM1 was validated as an independent prognostic factor. The associations of CHK1/MEK and AURKA/BET inhibitors were identified as the most potent amongst 528 tested pairwise drug combinations and their efficacy was validated in 3D spheroid models. The high synergism of AURKA/BET dual inhibition was confirmed in ex vivo and in vivo glioblastoma models, without detectable toxicity., Interpretation: Our work provides strong pre-clinical evidence of the efficacy of AURKA/BET inhibitor combination in glioblastoma and opens new therapeutic avenues for this unmet medical need. Besides, we established the proof-of-concept of a stepwise approach aiming at exploiting drug poly-pharmacology to unveil druggable cancer vulnerabilities and to fast-track the identification of synergistic combinations against refractory cancers., Funding: This study was funded by institutional grants and charities., Competing Interests: Declaration of interests The authors have declared no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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72. Primary central nervous system lymphoma (PCNSL) in older patients.
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Bertucci A, Harlay V, Chinot O, and Tabouret E
- Subjects
- Aged, Humans, Combined Modality Therapy, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Central Nervous System, Hematopoietic Stem Cell Transplantation, Central Nervous System Neoplasms drug therapy, Lymphoma drug therapy
- Abstract
Introduction: Primary central nervous system lymphoma (PCNSL) is a rare, chemo and radio-sensitive tumor limited to the central nervous system. The incidence of PCSNL increases notably in the elderly population which represented approximately half of the patients. The limit of 'elderly' population remained debated and nonuniform, including 60 years as a cutoff for brain radiotherapy, 65 years for autologous stem-cell transplantation, and 70 years for the last clinical trials. Current therapeutic options include first line treatment based on high-dose methotrexate based polychemotherapy, consolidation chemotherapy, and adapted autologous stem cell transplantation for highly selected patients. At relapse, single agent targeted therapies or salvage chemotherapy followed by intensive consolidation are promising therapeutic options. Nevertheless, improving management of elderly patients is an urgent medical need that currently remains unresolved., Objective: We will focus on elderly patients with PCNSL and their specificities including clinical presentations, available therapeutic options and adaptations to be made., Conclusion: To improve survival, it will be necessary to personalized and adapt the treatments, to each patient and his comorbidities, to increase their effectiveness and limit their toxicity in this frail population. Finally, inclusion of these patients in clinical trials is one of the major challenges to significantly change PCNSL elderly patient prognosis., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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73. Phase III study of the European Organisation for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire.
- Author
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van Leeuwen M, Kieffer JM, Young TE, Annunziata MA, Arndt V, Arraras JI, Autran D, Hani HB, Chakrabarti M, Chinot O, Cho J, da Costa Vieira RA, Darlington AS, Debruyne PR, Dirven L, Doege D, Eller Y, Eichler M, Fridriksdottir N, Gioulbasanis I, Hammerlid E, van Hemelrijck M, Hermann S, Husson O, Jefford M, Johansen C, Kjaer TK, Kontogianni M, Lagergren P, Lidington E, Lisy K, Morag O, Nordin A, Al Omari ASH, Pace A, De Padova S, Petranovia D, Pinto M, Ramage J, Rammant E, Reijneveld J, Serpentini S, Sodergren S, Vassiliou V, Leeuw IV, Vistad I, Young T, Aaronson NK, and van de Poll-Franse LV
- Subjects
- Humans, Male, Middle Aged, Quality of Life, Survivorship, Surveys and Questionnaires, Cancer Survivors, Neoplasms therapy, Neoplasms diagnosis
- Abstract
Purpose: The purpose of this study is to develop a European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) questionnaire that captures the full range of physical, mental, and social health-related quality of life (HRQOL) issues relevant to disease-free cancer survivors. In this phase III study, we pretested the provisional core questionnaire (QLQ-SURV111) and aimed to identify essential and optional scales., Methods: We pretested the QLQ-SURV111 in 492 cancer survivors from 17 countries with one of 11 cancer diagnoses. We applied the EORTC QLG decision rules and employed factor analysis and item response theory (IRT) analysis to assess and, where necessary, modify the hypothesized questionnaire scales. We calculated correlations between the survivorship scales and the QLQ-C30 summary score and carried out a Delphi survey among healthcare professionals, patient representatives, and cancer researchers to distinguish between essential and optional scales., Results: Fifty-four percent of the sample was male, mean age was 60 years, and, on average, time since completion of treatment was 3.8 years. Eleven items were excluded, resulting in the QLQ-SURV100, with 12 functional and 9 symptom scales, a symptom checklist, 4 single items, and 10 conditional items. The essential survivorship scales consist of 73 items., Conclusions: The QLQ-SURV100 has been developed to assess comprehensively the HRQOL of disease-free cancer survivors. It includes essential and optional scales and will be validated further in an international phase IV study., Implications for Cancer Survivors: The availability of this questionnaire will facilitate a standardized and robust assessment of the HRQOL of disease-free cancer survivors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
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74. Long-term survival with IDH wildtype glioblastoma: first results from the ETERNITY Brain Tumor Funders' Collaborative Consortium (EORTC 1419).
- Author
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Hertler C, Felsberg J, Gramatzki D, Le Rhun E, Clarke J, Soffietti R, Wick W, Chinot O, Ducray F, Roth P, McDonald K, Hau P, Hottinger AF, Reijneveld J, Schnell O, Marosi C, Glantz M, Darlix A, Lombardi G, Krex D, Glas M, Reardon DA, van den Bent M, Lefranc F, Herrlinger U, Razis E, Carpentier AF, Phillips S, Rudà R, Wick A, Tabouret E, Meyronet D, Maurage CA, Rushing E, Rapkins R, Bumes E, Hegi M, Weyerbrock A, Aregawi D, Gonzalez-Gomez C, Pellerino A, Klein M, Preusser M, Bendszus M, Golfinopoulos V, von Deimling A, Gorlia T, Wen PY, Reifenberger G, and Weller M
- Subjects
- Humans, Female, Young Adult, Adult, Middle Aged, Aged, Male, Isocitrate Dehydrogenase genetics, DNA Methylation, Neoplasm Recurrence, Local genetics, Prognosis, DNA Modification Methylases genetics, DNA Repair Enzymes genetics, Retrospective Studies, Glioblastoma genetics, Glioblastoma therapy, Glioblastoma pathology, Brain Neoplasms genetics, Brain Neoplasms therapy, Brain Neoplasms diagnosis
- Abstract
Background: Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined., Methods: European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by the Brain Tumor Funders Collaborative in the US and the EORTC Brain Tumor Group. Patients with glioblastoma surviving at least 5 years from diagnosis were identified at 24 sites in Europe, US, and Australia. In patients with isocitrate dehydrogenase (IDH) wildtype tumours, prognostic factors were analysed using the Kaplan-Meier method and the Cox proportional hazards model. A population-based reference cohort was obtained from the Cantonal cancer registry Zurich., Results: At the database lock of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 incompletely characterised) had been registered. In the IDH wildtype population, median age was 56 years (range 24-78 years), 96 patients (50.8%) were female, 139 patients (74.3%) had tumours with O
6 -methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (95% confidence interval [95% CI] 7.9-11.9). Patients without recurrence experienced longer median survival (not reached) than patients with one or more recurrences (8.92 years) (p < 0.001) and had a high rate (48.8%) of MGMT promoter-unmethylated tumours., Conclusions: Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Patients without relapse often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C.H. has received a research grant for protected time by the Filling the Gap foundation and honoraria for lecture from Vifor; E.L.R. has received honoraria for lectures or advisory board from Bayer, Janssen, Leo Pharma, Pierre Fabre, Seattle Genetics; J.C. has received research funding from Servier and Merck and consultant for Servier; R.S. reports consultation for Bayer, Astra Zeneca; W.W. reports consultation for Apogenix, Astra Zeneca, Bayer, Enterome, Medac, MSD and Roche/Genentech with honoraria paid to the Medical Faculty at the University of Heidelberg; F.D. has received honoraria for lectures or advisory board participation from Novocure; P.R. has received honoraria for lectures or advisory board participation from Bristol-Myers Squibb, Boehringer Ingelheim, Debiopharm, Merck Sharp and Dohme, Midatech, Novocure, QED, and Roche and research support from Merck Sharp and Dohme and Novocure; P.H. has received honoraria for lectures or advisory board participation or consulting from Bayer, Lilly, medac, Novartis, Novocure and Seagen; A.H. has received honoraria for lectures, consultation or advisory board participation from Novocure and Novartis; G.L. has received funding for a consulting or advisory role from Bayer, AbbVie, Orbus Therapeutics, BrainFarm, Health4U, Novartis, Braun and Janssen, and funding for travel from Roche, Bayer, and Ipsen; D.K. has received honoraria for lectures, consultation or advisory board participation from Novocure and BrainLab; M.G. reports honoraria from Roche, Novartis, UCB, AbbVie, Daiichi Sankyo, Novocure, Seagen, Bayer, Janssen-Cilag, Medac, Merck, Kyowa Kirin, travel support from Novocure and Medac, research grant from Novocure; D.R. reports support from Agenus, Agios; AnHeart Therapeutics, Avita Biomedical, Inc., Blue Rock Therapeutics, Bristol Myers Squibb, Boston Biomedica, CureVac AG, Del Mar Pharma, DNAtrix, Enterome, Hoffman-LaRoche, Ltd, Imvax, Janssen, Kiyatec, Medicenna Therapeutics, Neuvogen, Novartis, Novocure, Pyramid Bio, Sumitomo Dainippon Pharma. Vivacitas Oncology, Inc, Y-mabs Therapeutics; M.v.d.B has received honoraria for consultancy from Genenta, Servier, Astra Zeneca, Boehringer-Ingelheim, Carthera, Nerviano, Chimerix, Roche, Fore Biotherapeutics, Menarini-Stemline, Incyte and Sumitomo Pharma Oncology; F.L. received research funding from the Fonds Erasme; U.H. reports honoraria for lectures and and/or advisory board participation from Medac, Janssen, Bayer; E.R. reports travels grants BMS, Pfizer, MSD, Sanofi, Roche, Karyo labs Honorarium MSD, Servier; AF.C. received honoraria for lectures and/or advisory board participation from Gilead, Novartis; R.Ru. has received honoraria for lectures or consultation or advisory board from UCB, Novocure, Bayer, Genenta; M.P. has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals; P.W. has received research support from Astra Zeneca/Medimmune, Beigene, Celgene, Chimerix, Eli Lily, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Puma, Servier, Vascular Biogenics, VBI Vaccines and honoraria for advisory board participation or serving on data safety monitoring board from Astra Zeneca, Bayer, Black Diamond, Celularity, Chimerix, Day One Bio, Genenta, Novartis, Prelude Therapeutics, Sapience, Servier, Sagimet, Vascular Biogenics, VBI Vaccines; MW has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Medac, Merck (EMD), Novartis, Orbus, and Philogen. All remaining authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2023
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75. Optic Nerve Sheath Meningiomas: Solving Diagnostic Challenges with 68 Ga-DOTATOC PET/CT.
- Author
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Horowitz T, Salgues B, Padovani L, Farah K, Dufour H, Chinot O, Guedj E, and Graillon T
- Abstract
68 Ga-DOTATOC PET could be a noninvasive, highly sensitive, and specific technique for the challenging diagnosis of optic nerve sheath meningioma (ONSM). Our objective was to report the use and results of68 Ga-DOTATOC PET in suspected ONSM. Twelve subjects who underwent68 Ga-DOTATOC PET for suspected ONSM in our department were retrospectively included. Standardised clinical and radiological data were collected. The PET examination results were classified as positive or negative, and lesion standardised uptake values (SUVmax ) were recorded.68 Ga-DOTATOC PET confirmed positive uptake in six cases (SUVmax > 5), leading to ONSM diagnoses followed by radiation therapy in patients with vision loss. Six68 Ga-DOTATOC PET scans were considered negative (SUVmax < 5); these comprised one case of neurosarcoidosis, one cavernous malformation, and four uncertain diagnoses, leading to further investigation.68 Ga-DOTATOC PET was helpful in tumour volume delineation before radiation therapy, leading to a decrease in dose exposure. Noninvasive68 Ga-DOTATOC PET should be performed before treating nonhistologically proven meningiomas with radiotherapy or stereotactic radiosurgery, particularly in cases of uncertain diagnosis with MRI, which characterises most ONSM cases. PET SUVmax thresholds to distinguish meningioma from nonspecific uptake in other lesions need to be adapted to ONSM.68 Ga-DOTATOC PET improves the intraorbital lesion diagnostic approach and therefore impacts therapeutic management.- Published
- 2023
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76. Innovative treatments for meningiomas.
- Author
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Graillon T, Tabouret E, Salgues B, Horowitz T, Padovani L, Appay R, Farah K, Dufour H, Régis J, Guedj E, Barlier A, and Chinot O
- Subjects
- Humans, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, Proto-Oncogene Proteins c-akt therapeutic use, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases therapeutic use, Neoplasm Recurrence, Local, Mutation, Meningioma genetics, Meningioma therapy, Meningioma metabolism, Meningeal Neoplasms genetics, Meningeal Neoplasms therapy, Meningeal Neoplasms metabolism
- Abstract
Multi-recurrent high-grade meningiomas remain an unmet medical need in neuro-oncology when iterative surgeries and radiation therapy sessions fail to control tumor growth. Nevertheless, the last 10years have been marked by multiple advances in the comprehension of meningioma tumorigenesis via the discovery of new driver mutations, the identification of activated intracellular signaling pathways, and DNA methylation analyses, providing multiple potential therapeutic targets. Today, Anti-VEGF and mTOR inhibitors are the most used and probably the most active drugs in aggressive meningiomas. Peptide radioactive radiation therapy aims to target SSTR2A receptors, which are strongly expressed in meningiomas, but have an insufficient effect in most aggressive meningiomas, requiring the development of new techniques to increase the dose applied to the tumor. Based on the multiple potential intracellular targets, multiple targeted therapy clinical trials targeting Pi3K-Akt-mTOR and MAP kinase pathways as well as cell cycle and particularly, cyclin D4-6 are ongoing. Recently discovered driver mutations, SMO, Akt, and PI3KCA, offer new targets but are mostly observed in benign meningiomas, limiting their clinical relevance mainly to rare aggressive skull base meningiomas. Therefore, NF2 mutation remains the most frequent mutation and main challenging target in high-grade meningioma. Recently, inhibitors of focal adhesion kinase (FAK), which is involved in tumor cell adhesion, were tested in a phase 2 clinical trial with interesting but insufficient activity. The Hippo pathway was demonstrated to interact with NF2/Merlin and could be a promising target in NF2-mutated meningiomas with ongoing multiple preclinical studies and a phase 1 clinical trial. Recent advances in immune landscape comprehension led to the proposal of the use of immunotherapy in meningiomas. Except in rare cases of MSH2/6 mutation or high tumor mass burden, the activity of PD-1 inhibitors remains limited; however, its combination with various radiation therapy modalities is particularly promising. On the whole, therapeutic management of high-grade meningiomas is still challenging even with multiple promising therapeutic targets and innovations., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)
- Published
- 2023
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77. Contribution of nuclear medicine to the diagnosis and management of primary brain tumours.
- Author
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Horowitz T, Tabouret E, Graillon T, Salgues B, Chinot O, Verger A, and Guedj E
- Subjects
- Humans, Fluorodeoxyglucose F18, Neoplasm Recurrence, Local, Positron-Emission Tomography methods, Amino Acids, Radiopharmaceuticals, Nuclear Medicine, Meningioma diagnostic imaging, Meningioma therapy, Glioma diagnostic imaging, Glioma therapy, Brain Neoplasms diagnostic imaging, Brain Neoplasms therapy, Meningeal Neoplasms, Lymphoma
- Abstract
Positron emission tomography (PET) is a powerful tool that can help physicians manage primary brain tumours at diagnosis and follow-up. In this context, PET imaging is used with three main types of radiotracers:
18 F-FDG, amino acid radiotracers, and68 Ga conjugated to somatostatin receptor ligands (SSTRs). At initial diagnosis,18 F-FDG helps to characterize primary central nervous system (PCNS) lymphomas and high-grade gliomas, amino acid radiotracers are indicated for gliomas, and SSTR PET ligands are indicated for meningiomas. Such radiotracers provide information on tumour grade or type, assist in directing biopsies and help with treatment planning. During follow-up, in the presence of symptoms and/or MRI modifications, the differential diagnosis between tumour recurrence and post-therapeutic changes, in particular radiation necrosis, may be challenging, and there is strong interest in using PET to evaluate therapeutic toxicity. PET may also contribute to identifying specific complications, such as postradiation therapy encephalopathy, encephalitis associated with PCNS lymphoma, and stroke-like migraine after radiation therapy (SMART) syndrome associated with glioma recurrence and temporal epilepsy, originally illustrated in this review. This review summarizes the main contribution of PET to the diagnosis, management, and follow-up of brain tumours, specifically gliomas, meningiomas, and primary central nervous system lymphomas., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)- Published
- 2023
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78. Radio-chemotherapy feasibility for biopsy-only unresectable IDH wild-type glioblastomas (BO-GBM).
- Author
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Harlay V, Appay R, Bequet C, Petrirena G, Campello C, Barrié M, Autran D, Graillon T, Boissonneau S, Dufour H, Figarella-Branger D, Padovani L, Barlier A, Nanni I, Tabouret E, and Chinot O
- Abstract
Background: "Biopsy-only" glioblastoma (BO-GBM) is a heterogeneous, understudied group of patients associated with a poor outcome. Our objective was to explore the pattern of care and prognosis associated with BO-GBM in our center., Methods: Patients with IDH wild-type BO-GBM included in a prospective regional cohort initiated in 2014 and closed in 2017 were retrospectively reviewed for patient characteristics, MRI findings, treatment allocation, and delivery., Results: Of 535 patients included in the cohort, 137 patients were included in the present analysis. The median age was 66 years old and the median KPS was 70. Forty-six patients (33.6%) were referred to radiotherapy and chemotherapy (RT-TMZ) regimen, 75 (54.7%), considered unfitted for RT, received chemotherapy upfront (CT) and 16 (11.7%) were referred to palliative care (PC). Regarding the first group, 91% of patients completed the RT-TMZ. In the CT group, 11 of 75 patients (14.7%) underwent radiotherapy after chemotherapy upfront. Median overall survival was 12.3 months (95% CI, 15.30-24.16), 5.7 months (95% CI, 6.22-9.20), and 1.9 months (95% CI, 1.43-5.08) in RT-TMZ, CT, and PC groups, respectively. In multivariate analyses, progression-free survival was impacted by baseline KPS ( P < .001) and MGMT status ( P = .004). Overall survival was impacted by baseline KPS ( P < .001) and age ( P = .030)., Conclusion: BO-GBM constitute a large and heterogeneous population in which one-third of patients is amenable to the standard of care, with survival outcome close to one of the patients who underwent surgery. Reliable criteria are needed to help select patients for adequate treatment while new strategies are warranted for BO-GBM unfit for RT., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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79. Association of antidepressant drug use with outcome of patients with glioblastoma.
- Author
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Seliger C, Oppong FB, Lefranc F, Chinot O, Stupp R, Nabors B, Gorlia T, and Weller M
- Subjects
- Humans, Antidepressive Agents adverse effects, Anticonvulsants therapeutic use, Fatigue, Glioblastoma drug therapy
- Abstract
Depressive symptoms are common among patients with glioblastoma, but patients are often not treated with antidepressants. There is only limited evidence on the association of antidepressant drug use with survival in glioblastoma. We performed a pooled analysis of patients treated within the CENTRIC, CORE, AVAglio and ACT-IV trials to explore the relation of antidepressant drug use with progression-free (PFS) and overall survival (OS) at baseline, at the start of maintenance therapy and at the start of maintenance cycle 4. We further assessed the association of antidepressant drugs with seizure, cognition, fatigue and a diagnosis of depression. Among more than 1700 patients, we found no significant association between the use of antidepressants at baseline or at the start of maintenance therapy and PFS or OS. However, we found OS, but not PFS, to be significantly worse in patients using antidepressants at the start of maintenance cycle 4. After adjustment for antiepileptic drug use and despite showing a trend for increased risk, seizures were not significantly associated with antidepressant drug use, nor was there a change in mini mental state examination (MMSE) scores or fatigue by antidepressant drug use at baseline. However, there was a significant positive association between antidepressant use at the start of maintenance treatment and fatigue during maintenance treatment. The association of antidepressant use at the start of maintenance cycle 4 with inferior OS of glioblastoma patients requires independent confirmation and further study. Further prospective trials should evaluate efficacy, side effects and associations with outcome of antidepressants in glioblastoma., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2023
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80. Incidence and characteristics of pseudoprogression in IDH-mutant high-grade gliomas: A POLA network study.
- Author
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Seyve A, Dehais C, Chinot O, Djelad A, Cohen-Moyal E, Bronnimann C, Gourmelon C, Emery E, Colin P, Boone M, Vauléon E, Langlois O, di Stefano AL, Seizeur R, Ghiringhelli F, D'Hombres A, Feuvret L, Guyotat J, Capelle L, Carpentier C, Garnier L, Honnorat J, Meyronet D, Mokhtari K, Figarella-Branger D, and Ducray F
- Subjects
- Humans, Retrospective Studies, Incidence, Magnetic Resonance Imaging, Isocitrate Dehydrogenase genetics, Mutation, Brain Neoplasms epidemiology, Brain Neoplasms genetics, Brain Neoplasms therapy, Glioma epidemiology, Glioma genetics, Glioma therapy
- Abstract
Background: Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described., Methods: We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (RT) (with or without chemotherapy [CT]), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n = 200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n = 543) based on progression-free survival before and after first progression., Results: In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after RT. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted of the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after RT. The only factor associated with pseudoprogression occurrence was adjuvant PCV CT. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions., Conclusion: In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after RT, the possibility of a pseudoprogression should be carefully considered., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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81. Molecular and clinical diversity in primary central nervous system lymphoma.
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Hernández-Verdin I, Kirasic E, Wienand K, Mokhtari K, Eimer S, Loiseau H, Rousseau A, Paillassa J, Ahle G, Lerintiu F, Uro-Coste E, Oberic L, Figarella-Branger D, Chinot O, Gauchotte G, Taillandier L, Marolleau JP, Polivka M, Adam C, Ursu R, Schmitt A, Barillot N, Nichelli L, Lozano-Sánchez F, Ibañez-Juliá MJ, Peyre M, Mathon B, Abada Y, Charlotte F, Davi F, Stewart C, de Reyniès A, Choquet S, Soussain C, Houillier C, Chapuy B, Hoang-Xuan K, and Alentorn A
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- Humans, Phosphatidylinositol 3-Kinases genetics, Mutation, Polycomb Repressive Complex 2 genetics, Central Nervous System pathology, Lymphoma, Large B-Cell, Diffuse pathology, Central Nervous System Neoplasms genetics, Central Nervous System Neoplasms pathology
- Abstract
Background: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity., Patients and Methods: To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data., Results: Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue., Conclusions: The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions., Competing Interests: Disclosure GA reports grants from Biogen, Novartis, Roche, Sanofi, Abbvie, Pfizer, and CSL Behring, outside the submitted work. AA reports research grant with an unrestricted grant from Bristol Myers Squibb (BMS). All other authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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82. Plasma nanoDSF Denaturation Profile at Baseline Is Predictive of Glioblastoma EGFR Status.
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Eyraud R, Ayache S, Tsvetkov PO, Kalidindi SS, Baksheeva VE, Boissonneau S, Jiguet-Jiglaire C, Appay R, Nanni-Metellus I, Chinot O, Devred F, and Tabouret E
- Abstract
Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor in adults. Recently, we demonstrated that plasma denaturation profiles of glioblastoma patients obtained using Differential Scanning Fluorimetry can be automatically distinguished from healthy controls with the help of Artificial Intelligence (AI). Here, we used a set of machine-learning algorithms to automatically classify plasma denaturation profiles of glioblastoma patients according to their EGFR status. We found that Adaboost AI is able to discriminate EGFR alterations in GBM with an 81.5% accuracy. Our study shows that the use of these plasma denaturation profiles could answer the unmet neuro-oncology need for diagnostic predictive biomarker in combination with brain MRI and clinical data, in order to allow for a rapid orientation of patients for a definitive pathological diagnosis and then treatment. We complete this study by showing that discriminating another mutation, MGMT, seems harder, and that post-surgery monitoring using our approach is not conclusive in the 48 h that follow the surgery.
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- 2023
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83. Isolated intraocular relapses of primary cerebral lymphomas: An LOC network study.
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Younan N, Soussain C, Choquet S, Cassoux N, Touitou V, Schmitt A, Chinot O, Oberic L, Damaj G, Houot R, Ghesquières H, Laribi K, Ahle G, Taillandier L, Paillassa J, Gyan E, Jardin F, Delwail V, Marolleau JP, Tempescul A, Agapé P, Bourniquel M, Vacheret F, Jdid I, Le Garff-Tavernier M, Malaise D, Alentorn A, Xuan KH, and Houillier C
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- Humans, Aged, Transplantation, Autologous, Retrospective Studies, Vitreous Body, Hematopoietic Stem Cell Transplantation, Retinal Neoplasms, Lymphoma
- Abstract
Most relapses of primary central nervous system lymphoma (PCNSL) occur in the brain and are associated with a poor prognosis. Isolated intraocular relapses (IIORs) are rare and poorly described. We retrospectively selected from the French Lymphome Oculo-Cérébral database PCNSL patients who initially presented with cerebral localization and who experienced IIOR during the course of the disease. Of the 1472 patients included in the database, 55 patients presented an IIOR. Their median age was 68 years, and median Karnofsky Performance Status 80. IL-10 levels in the aqueous humor and/or in the vitreous were increased in 42/46 patients. 45/55 patients received systemic chemotherapy, and 11/55 received high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) as consolidation treatment. After a median follow-up of 69 months, 42/55 patients had relapsed, including 90% of the patients who did not receive HCT-ASCT at IIOR and 40% of the patients who received HCT-ASCT at IIOR (p < 0.001). The first relapse after the initial IIOR was exclusively in the eye in 23/42 patients, and 29/42 patients had a subsequent brain relapse during the course of the disease. The median progression-free survival, brain-free survival and overall survival from IIOR were 12.2, 48.6 and 57.1 months, respectively. Isolated intraocular relapse is not exceptional in the course of PCNSL and deserves systematic ophthalmological follow-up. Its prognosis is much better than the prognosis of brain relapse, with an evolution close to that of primary vitreoretinal lymphoma. With the exception of patients who received HCT-ASCT at IIOR, almost all patients subsequently relapsed, often with other IIORs., (© 2022 John Wiley & Sons Ltd.)
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- 2022
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84. Factors associated with health-related quality of life (HRQoL) deterioration in glioma patients during the progression-free survival period.
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Coomans MB, Dirven L, Aaronson N, Baumert BG, van den Bent M, Bottomley A, Brandes AA, Chinot O, Coens C, Gorlia T, Herrlinger U, Keime-Guibert F, Malmström A, Martinelli F, Stupp R, Talacchi A, Weller M, Wick W, Reijneveld JC, and Taphoorn MJB
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- Humans, Quality of Life, Progression-Free Survival, Brain Neoplasms therapy, Glioma
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Background: Maintenance of functioning and well-being during the progression-free survival (PFS) period is important for glioma patients. This study aimed to determine whether health-related quality of life (HRQoL) can be maintained during progression-free time, and factors associated with HRQoL deterioration in this period., Methods: We included longitudinal HRQoL data from previously published clinical trials in glioma. The percentage of patients with stable HRQoL until progression was determined per scale and at the individual patient level (i.e. considering all scales simultaneously). We assessed time to a clinically relevant deterioration in HRQoL, expressed in deterioration-free survival and time-to-deterioration (the first including progression as an event). We also determined the association between sociodemographic and clinical factors and HRQoL deterioration in the progression-free period., Results: Five thousand five hundred and thirty-nine patients with at least baseline HRQoL scores had a median time from randomization to progression of 7.6 months. Between 9-29% of the patients deteriorated before disease progression on the evaluated HRQoL scales. When considering all scales simultaneously, 47% of patients deteriorated on ≥1 scale. Median deterioration-free survival period ranged between 3.8-5.4 months, and median time-to-deterioration between 8.2-11.9 months. For most scales, only poor performance status was independently associated with clinically relevant HRQoL deterioration in the progression-free period., Conclusions: HRQoL was maintained in only 53% of patients in their progression-free period, and treatment was not independently associated with this deterioration in HRQoL. Routine monitoring of the patients' functioning and well-being during the entire disease course is therefore important, so that interventions can be initiated when problems are signaled., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
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- 2022
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85. Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study.
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Houillier C, Dureau S, Taillandier L, Houot R, Chinot O, Moluçon-Chabrot C, Schmitt A, Gressin R, Choquet S, Damaj G, Peyrade F, Abraham J, Delwail V, Gyan E, Sanhes L, Cornillon J, Garidi R, Delmer A, Al Jijakli A, Morel P, Waultier A, Paillassa J, Chauchet A, Gastinne T, Laadhari M, Plissonnier AS, Feuvret L, Cassoux N, Touitou V, Ricard D, Hoang-Xuan K, and Soussain C
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- Humans, Middle Aged, Adolescent, Young Adult, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Neoplasm Recurrence, Local drug therapy, Transplantation, Autologous, Combined Modality Therapy, Central Nervous System Neoplasms pathology, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Lymphoma radiotherapy, Lymphoma drug therapy
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported the results of a randomized phase II study in patients with newly diagnosed primary CNS lymphoma (age 18-60 years). Patients were treated with high-dose methotrexate-based induction chemotherapy followed by whole-brain radiotherapy (WBRT) or high-dose chemotherapy (thiotepa-busulfan-cyclophosphamide) with autologous stem-cell transplantation (ASCT). The median follow-up was 33 months. In this report, we provide long-term data (median follow-up, 8 years) regarding the outcomes and toxicities. Fifty-three and 44 patients received induction chemotherapy followed by WBRT or ASCT, respectively. Their 8-year event-free survival from random assignment was 67% and 39% in the ASCT and WBRT arms, respectively ( P = .03), with a significantly lower risk of relapse after ASCT (hazard ratio, 0.13; P < .001). One third of patients who relapsed after WBRT were alive after salvage treatment. Five and four patients died of ASCT and WBRT-related toxicities, respectively. The 8-year overall survival was 69% and 65% in the ASCT and WBRT arms, respectively (not significant). Balance (52% v 10%, P ≤ 0.001) and neurocognition (64% v 13%, P < .001) significantly deteriorated after WBRT compared with ASCT during the follow-up. This study shows that 40 Gy WBRT should be avoided in first-line treatment because of its neurotoxicity and suboptimal efficacy in reducing relapses while ASCT appears to be highly efficient in preventing relapses.
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- 2022
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86. Characteristics, Patterns of Care and Predictive Geriatric Factors in Elderly Patients Treated for High-Grade IDH -Mutant Gliomas: A French POLA Network Study.
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Montégut C, Guillamo JS, Ducray F, Dehais C, Cohen-Jonathan Moyal E, Desenclos C, Petit A, Seizeur R, Bekaert L, Gaultier C, Motuo Fotso MJ, Blonski M, Frenel JS, Vauléon E, Langlois O, Noel G, Carpentier AF, Di Stefano AL, Bronnimann C, Figarella-Branger D, Chinot O, and Tabouret E
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Background: Describe the characteristics, patterns of care, and predictive geriatric factors of elderly patients with IDHm high-grade glioma (HGG) included in the French POLA network. Material and Methods: The characteristics of elderly (≥70 years) patients IDHm HGG were compared to those of younger patients IDHm HGG (<70 years) and of elderly patients IDHwt HGG. Geriatric features were collected. Results: Out of 1433 HGG patients included, 119 (8.3%) were ≥70 years. Among them, 39 presented with IDHm HGG. The main characteristics of elderly IDHm HGG were different from those of elderly IDHwt HGG but similar to those of younger IDHm HGG. In contrast, their therapeutic management was different from those of younger IDHm HGG with less frequent gross total resection and radiotherapy. The median progression-free survival (PFS) and overall survival (OS) were longer for elderly patients IDHm HGG (29.3 months and 62.1 months) than elderly patients IDHwt HGG (8.3 months and 13.3 months) but shorter than those of younger patients IDHm HGG (69.1 months and not reached). Geriatric factors associated with PFS and OS were mobility, neuropsychological disorders, body mass index, and autonomy. Geriatric factors associated with PFS and OS were mobility, neuropsychological disorders, and body mass index, and autonomy. Conclusion: the outcome of IDHm HGG in elderly patients is better than that of IDHwt HGG. Geriatric assessment may be particularly important to optimally manage these patients.
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- 2022
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87. Soluble CD146, a biomarker and a target for preventing resistance to anti-angiogenic therapy in glioblastoma.
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Joshkon A, Tabouret E, Traboulsi W, Bachelier R, Simoncini S, Roffino S, Jiguet-Jiglaire C, Badran B, Guillet B, Foucault-Bertaud A, Leroyer AS, Dignat-George F, Chinot O, Fayyad-Kazan H, Bardin N, and Blot-Chabaud M
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- Mice, Animals, Humans, Bevacizumab pharmacology, Bevacizumab therapeutic use, CD146 Antigen metabolism, Mice, Nude, Integrin alphaVbeta3 therapeutic use, Neoplasm Recurrence, Local drug therapy, Biomarkers, Glioblastoma pathology, Brain Neoplasms pathology
- Abstract
Rationale: Glioblastoma multiforme (GBM) is a primary brain tumor with poor prognosis. The U.S. food and drug administration approved the use of the anti-VEGF antibody bevacizumab in recurrent GBM. However, resistance to this treatment is frequent and fails to enhance the overall survival of patients. In this study, we aimed to identify novel mechanism(s) responsible for bevacizumab-resistance in CD146-positive glioblastoma., Methods: The study was performed using sera from GBM patients and human GBM cell lines in culture or xenografted in nude mice., Results: We found that an increase in sCD146 concentration in sera of GBM patients after the first cycle of bevacizumab treatment was significantly associated with poor progression free survival and shorter overall survival. Accordingly, in vitro treatment of CD146-positive glioblastoma cells with bevacizumab led to a high sCD146 secretion, inducing cell invasion. These effects were mediated through integrin αvβ3 and were blocked by mucizumab, a novel humanized anti-sCD146 antibody. In vivo, the combination of bevacizumab with mucizumab impeded CD146 + glioblastoma growth and reduced tumor cell dissemination to an extent significantly higher than that observed with bevacizumab alone., Conclusion: We propose sCD146 to be 1/ an early biomarker to predict and 2/ a potential target to prevent bevacizumab resistance in patients with glioblastoma., (© 2022. The Author(s).)
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- 2022
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88. Surgery for glioblastomas in the elderly: an Association des Neuro-oncologues d'Expression Française (ANOCEF) trial.
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Laigle-Donadey F, Metellus P, Guyotat J, Menei P, Proust F, Dufour H, Chinot O, Honnorat J, Faillot T, Paquis P, Peruzzi P, Emery E, Guillamo JS, Carpentier A, Wager M, Lebbah S, Hajage D, Delattre JY, and Cornu P
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- Humans, Aged, Antineoplastic Agents, Alkylating therapeutic use, Quality of Life, Dacarbazine therapeutic use, Glioblastoma surgery, Brain Neoplasms surgery, Glioma drug therapy
- Abstract
Objective: The role of surgery in the treatment of malignant gliomas in the elderly is not settled. The authors conducted a randomized trial that compared tumor resection with biopsy only-both followed by standard therapy-in such patients., Methods: Patients ≥ 70 years of age with a Karnofsky Performance Scale (KPS) score ≥ 50 and presenting with a radiological suspicion of operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy groups. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008-2017), with the addition of adjunct therapy with temozolomide when this regimen became standard (2017-2019). The primary endpoint was survival, and secondary endpoints were progression-free survival (PFS), cognitive status (Mini-Mental State Examination), autonomy (KPS), quality of life (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-BN20), and perioperative morbidity and mortality., Results: Between 2008 and 2019, 107 patients from 9 centers were enrolled in the study; 101 were evaluable for analysis because a GBM was histologically confirmed (50 in the surgery arm and 51 in the biopsy arm). There was no statistically significant difference in median survival between the surgery (9.37 months) and the biopsy (8.96 months, p = 0.36) arms (adjusted HR 0.79, 95% CI 0.52-1.21, p = 0.28). However, the surgery group had an increased PFS (5.06 vs 4.02 months; p = 0.034) (adjusted HR 0.50, 95% CI 0.32-0.78, p = 0.002). Less deterioration of quality of life and KPS score evolution than in the biopsy group was observed. Surgery was not associated with increased mortality or morbidity., Conclusions: This study suggests that debulking surgery is safe, and-compared to biopsy-is associated with a less severe deterioration of quality of life and autonomy, as well as a significant although modest improvement of PFS in elderly patients suffering from newly diagnosed malignant glioma. Although resection does not provide a significant survival benefit in the elderly, the authors believe that the risk/benefit analysis favors an attempt at optimal tumor resection in this population, provided there is careful preoperative geriatric evaluation. Clinical trial registration no.: NCT02892708 (ClinicalTrials.gov).
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- 2022
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89. Co-Targeting MAP Kinase and Pi3K-Akt-mTOR Pathways in Meningioma: Preclinical Study of Alpelisib and Trametinib.
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Mondielli G, Mougel G, Darriet F, Roche C, Querdray A, Lisbonis C, Appay R, Dufour H, Chinot O, Graillon T, and Barlier A
- Abstract
Recurrent or high-grade meningiomas are an unmet medical need. Recently, we demonstrated that targeting mTOR by everolimus was relevant both in vitro and in humans. However, everolimus induces an AKT activation that may impact the anti-proliferative effect of the drug. Moreover, the MAP kinase pathway was shown to be involved in meningioma tumorigenesis. We therefore targeted both the Pi3k-AKT-mTOR and MAP kinase pathways by using combinations of the Pi3k inhibitor alpelisib and the MEK inhibitor trametinib. Our study was performed in vitro on the human meningioma cell lines and on a large series of primary cultures providing from 63 freshly operated meningiomas including 35 WHO grade 1, 23 grade 2, and five grade 3, half of which presented a NF2 genomic alteration. Alpelisib induced a higher inhibitory effect on cell viability and proliferation than everolimus in all cell lines and 32 randomly selected tumors no matter the genomic status, the histological subtype or grade. Trametinib also strongly inhibited cell proliferation and induced AKT activation. Combined treatment with alpelisib plus trametinib reversed the AKT activation induced by trametinib and induced an additive inhibitory effect irrespective of the cell lines or tumor features. Co-targeting pathways seems promising and may be considered particularly for aggressive meningioma.
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- 2022
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90. Incidence, molecular characteristics, and imaging features of "clinically-defined pseudoprogression" in newly diagnosed glioblastoma treated with chemoradiation.
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Hagiwara A, Schlossman J, Shabani S, Raymond C, Tatekawa H, Abrey LE, Garcia J, Chinot O, Saran F, Nishikawa R, Henriksson R, Mason WP, Wick W, Cloughesy TF, and Ellingson BM
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- Chemoradiotherapy methods, Disease Progression, Humans, Incidence, Magnetic Resonance Imaging, Reactive Oxygen Species, Brain Neoplasms diagnostic imaging, Brain Neoplasms therapy, Glioblastoma diagnostic imaging, Glioblastoma therapy
- Abstract
Purpose: Pseudoprogression (PsP) remains an elusive and clinically important, yet ill-defined, phenomena that, generally, involves a period of early radiographic progression (enhancement) followed by a period of radiographic stability or regression. In the current study, we utilized data from the control arm of a phase III clinical trial in newly-diagnosed glioblastoma to explore imaging characteristics of "clinically-defined PsP", or early radiographic progression (PFS < 6 months from chemoradiation) followed by a long post-progression residual overall survival (ROS > 12 months)., Methods: One hundred sixty-nine patients with newly-diagnosed GBM from the control arm of the AVAglio trial (NCT00943826) who presented with early radiographic progressive disease (PD) (< 6 months) were included. Clinical characteristics, topographical patterns, and radiomic features were compared between newly-diagnosed GBM exhibiting early PD and early death (< 12-month ROS, "true PD") with those exhibiting early PD and a long residual survival (> 12-month ROS, "clinically-defined PsP")., Results: "Clinically-defined PsP" occurred to 38.5% of patients with early PD, and was more associated with MGMT methylation (P = 0.02), younger age (P = 0.003), better neurological performance (P = 0.01), and lower contrast-enhancing tumor volume (P = 0.002) at baseline. GBM showing "true PD" occurred more frequently in the right internal capsule, thalamus, lentiform nucleus, and temporal lobe than those with "clinical PsP". Radiomic analysis predicted "clinical PsP" with > 70% accuracy on the validation dataset., Conclusion: Patients with early PD that eventually exhibit "clinically-defined PsP" have distinct clinical, molecular, and MRI characteristics. This information may be useful for treating clinicians to better understand the potential risks and outcome in patients exhibiting early radiographic changes following chemoradiation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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91. Prognostic significance of therapy-induced myelosuppression in newly diagnosed glioblastoma.
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Le Rhun E, Oppong FB, Vanlancker M, Stupp R, Nabors B, Chinot O, Wick W, Preusser M, Gorlia T, and Weller M
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- Antineoplastic Agents, Alkylating adverse effects, Chemoradiotherapy adverse effects, Female, Humans, Male, Prognosis, Temozolomide adverse effects, Brain Neoplasms, Glioblastoma, Lymphopenia chemically induced, Lymphopenia drug therapy
- Abstract
Background: Myelosuppression is the major toxicity encountered during temozolomide chemoradiotherapy for newly diagnosed glioblastoma., Methods: We assessed the association of myelosuppression (neutropenia, thrombocytopenia, anemia, and lymphopenia) during temozolomide chemoradiotherapy alone or in combination with experimental agents with progression-free survival (PFS) or overall survival (OS) in 2073 patients with newly diagnosed glioblastoma enrolled into five clinical trials: CENTRIC, CORE, EORTC 26082, AVAglio, and EORTC 26981. A landmark Cox model was used. For each primary association analysis, a significance level of 1.7% was used., Results: Lower neutrophil counts at baseline were associated with better PFS (P = .011) and OS (P < .001), independently of steroid intake. Females experienced uniformly more myelotoxicity than males. Lymphopenia during concomitant chemoradiotherapy was associated with OS (P = .009): low-grade (1-2) lymphopenia might be associated with superior OS (HR 0.78, 98.3% CI 0.58-1.06), whereas high-grade (3-4) lymphopenia might be associated with inferior OS (HR 1.08, 98.3% CI 0.75-1.54). There were no associations of altered hematological parameters during concomitant chemoradiotherapy with PFS. During maintenance chemoradiotherapy, no significant association was found between any parameter of myelosuppression and PFS or OS, although exploratory analysis at 5% significance level indicated that either mild-to-moderate (HR 0.76, 95% CI 0.62-0.93) or high-grade lymphopenia (HR 0.65, 95% CI 0.46-0.92) was associated with superior OS (P = .013), but not PFS., Conclusions: The association of higher neutrophil counts at baseline with inferior PFS and OS requires further prospective evaluation. The link of therapy-induced lymphopenia to better outcome may guide the design for immunotherapy trials in newly diagnosed glioblastoma., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2022
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92. Reduced-dose WBRT as consolidation treatment for patients with primary CNS lymphoma: an LOC network study.
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Lesueur P, Damaj G, Hoang-Xuan K, Roland V, Schmitt A, Chinot O, Fabbro M, Agapé P, Moluçon-Chabrot C, Chebrek S, Alentorn A, Feuvret L, Delgadillo D, Stefan D, Choquet S, Nichelli L, Mokhtari K, Mathon B, Dureau S, Soussain C, and Houillier C
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Humans, Middle Aged, Neoplasm Recurrence, Local drug therapy, Prospective Studies, Retrospective Studies, Transplantation, Autologous, Central Nervous System Neoplasms drug therapy, Hematopoietic Stem Cell Transplantation, Lymphoma, Non-Hodgkin therapy
- Abstract
The optimal consolidation strategy for primary central nervous system lymphoma (PCNSL) remains controversial. Preventing radio-induced neurotoxicity of consolidation treatment through reduced-dose whole-brain radiotherapy (rdWBRT) at a dose of 23.4 Gy is an interesting alternative to conventional WBRT in patients aged <60 years. From the LOC Network (Network for Oculo-cerebral Lymphomas) database, we retrospectively selected patients with PCNSL aged <60 years who showed complete (CR) or unconfirmed CR after high-dose methotrexate-based chemotherapy and had received consolidation rdWBRT as the first-line treatment. If available, prospective neuropsychological follow-ups were reported. Twenty-nine patients diagnosed between 2013 and 2018 met the study selection criteria. Nine (31%) patients experienced relapse during the follow-up, with a median time from radiotherapy to recurrence of 8.7 months (interquartile range, 4-11.5). Five of those patients received salvage treatment and consolidation with intensive chemotherapy and autologous stem cell transplantation. Progression-free survival rates were 89% (95% confidence interval [CI] 79%-100%), 72% (95% CI, 56%-88%), and 69% (95% CI, 52%-85%) at 1, 2, and 5 years, respectively. Overall survival rates were 100%, 89% (95% CI, 79%-100%), and 86% (95% CI, 74%-99%) at 1, 2, and 5 years, respectively, and were consistent with those observed for standard-dose WBRT (sdWBRT). No prognostic factor was identified. The results of the 36-month neuropsychological follow-up for a subset of patients appeared reassuring, with most patients exhibiting maintenance of or improvements in their baseline conditions. Our results, combined with phase 2 study results, support the use of rdWBRT instead of sdWBRT as a consolidation treatment in <60-year-old patients showing CR after induction treatment., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2022
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93. Somatostatin Receptor Theranostics for Refractory Meningiomas.
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Salgues B, Graillon T, Horowitz T, Chinot O, Padovani L, Taïeb D, and Guedj E
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- Humans, Positron-Emission Tomography, Precision Medicine, Radionuclide Imaging, Receptors, Somatostatin, Retrospective Studies, Treatment Outcome, Yttrium Radioisotopes, Meningeal Neoplasms radiotherapy, Meningioma radiotherapy
- Abstract
Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas progressing after surgery and radiotherapy. The aim of this study was to provide outcomes of patients harboring refractory meningiomas treated by 177Lu-DOTATATE and an overall analysis of progression-free survival at 6 months (PFS-6) of the same relevant studies in the literature. Eight patients with recurrent and progressive WHO grade II meningiomas were treated after multimodal pretreatment with 177Lu-DOTATATE between 2019 and 2022. Primary and secondarily endpoints were progression-free survival at 6-months (PFS-6) and toxicity, respectively. PFS-6 analysis of our case series was compared with other similar relevant studies that included 86 patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC. Our retrospective study showed a PFS-6 of 85.7% for WHO grade II progressive refractory meningiomas. Treatment was clinically and biologically well tolerated. The overall analysis of the previous relevant studies showed a PFS-6 of 89.7% for WHO grade I meningiomas ( n = 29); 57.1% for WHO grade II ( n = 21); and 0 % for WHO grade III ( n = 12). For all grades ( n = 86), including unknown grades, PFS-6 was 58.1%. SSTR-targeted PRRT allowed us to achieve prolonged PFS-6 in patients with WHO grade I and II progressive refractory meningiomas, except the most aggressive WHO grade II tumors. Large scale randomized trials are warranted for the better integration of PRRT in the treatment of refractory meningioma into clinical practice guidelines.
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- 2022
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94. Prognostic value of circulating lymphocyte subsets in primary central nervous system lymphoma.
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Berthelot A, Bequet C, Harlay V, Petrirena G, Campello C, Barrié M, Appay R, Chinot O, and Tabouret E
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Central Nervous System pathology, Humans, Lymphocyte Count, Lymphocyte Subsets, Prognosis, Retrospective Studies, Rituximab therapeutic use, Lymphoma, Large B-Cell, Diffuse pathology, Lymphopenia
- Abstract
Background: Immunity plays an important role in CNS-DLBCL development. CNS-DLBCL predictive factors need to be improved., Objective: To evaluate the predictive value of circulating lymphocyte subsets in PCNSL patients., Methods: We prospectively analyzed blood lymphocyte immunophenotyping (LIP) in newly CNS-DLBCL referred to our institution between December 2013 and January 2020. LIP analysis was performed before rituximab and chemotherapy administration. The clinical, radiological, histological, biological and treatment data were retrospectively collected., Results: Fifty-three patients were included with a median age of 69.7 (range 21.7-87.5). Median KPS was 60 (range 30-100). Thirty-three patients (64%) presented with one or several lymphopenias: 21 (40%), 24 (46%) and 9 (17%) NK, T and B lymphopenias respectively. Only 11 patients (21%) had normal LIP. Median CD4+/CD8+ ratio was 2.11 (range 0.54-9.11). This ratio was normal, low or high in 27%, 28% and 44% of patients respectively. The presence of steroids did not impact LIP results. Complete, partial responses, stable and progressive disease (PD) were observed in 24 (50%), 10 (21%), 4 (8%), and 10 (21%) patients respectively. CD4+/CD8+ ratio tended to be different between refractory (PD patients) and non-refractory patients (p = 0.077, ROC AUC: 0.684). Median progression-free survival (PFS) and overall survival (OS) were 14.7 (95%CI 6.5-22.9) and 43.2 (95%CI 21.6-64.9) months, respectively. In multivariate analyses, adjusted by KPS, a CD4+/CD8+ ratio > 1.97 was associated with poor PFS [p = 0.043, HR = 3.32 (1.02-4.88)] and tended to be associated with worse OS (p = 0.064)., Conclusion: LIP at baseline may predict refractory disease and exhibits a prognostic value in CNS-DLBCL patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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95. Associations of levetiracetam use with the safety and tolerability profile of chemoradiotherapy for patients with newly diagnosed glioblastoma.
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Seystahl K, Oppong FB, Le Rhun E, Hertler C, Stupp R, Nabors B, Chinot O, Preusser M, Gorlia T, and Weller M
- Abstract
Background: Levetiracetam (LEV) is one of the most frequently used antiepileptic drugs (AED) for brain tumor patients with seizures. We hypothesized that toxicity of LEV and temozolomide-based chemoradiotherapy may overlap., Methods: Using a pooled cohort of patients with newly diagnosed glioblastoma included in clinical trials prior to chemoradiotherapy (CENTRIC, CORE, AVAglio) or prior to maintenance therapy (ACT-IV), we tested associations of hematologic toxicity, nausea or emesis, fatigue, and psychiatric adverse events during concomitant and maintenance treatment with the use of LEV alone or with other AED versus other AED alone or in combination versus no AED use at the start of chemoradiotherapy and of maintenance treatment., Results: Of 1681 and 2020 patients who started concomitant chemoradiotherapy and maintenance temozolomide, respectively, 473 and 714 patients (28.1% and 35.3%) were treated with a LEV-containing regimen, 538 and 475 patients (32.0% and 23.5%) with other AED, and 670 and 831 patients (39.9% and 41.1%) had no AED. LEV was associated with higher risk of psychiatric adverse events during concomitant treatment in univariable and multivariable analyses (RR 1.86 and 1.88, P < .001) while there were no associations with hematologic toxicity, nausea or emesis, or fatigue. LEV was associated with reduced risk of nausea or emesis during maintenance treatment in multivariable analysis (HR = 0.80, P = .017) while there were no associations with hematologic toxicity, fatigue, or psychiatric adverse events., Conclusions: LEV is not associated with reduced tolerability of chemoradiotherapy in patients with glioblastoma regarding hematologic toxicity and fatigue. Antiemetic properties of LEV may be beneficial during maintenance temozolomide., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
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- 2022
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96. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life-experience of the French Network.
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Schenone L, Houillier C, Tanguy ML, Choquet S, Agbetiafa K, Ghesquières H, Damaj G, Schmitt A, Bouabdallah K, Ahle G, Gressin R, Cornillon J, Houot R, Marolleau JP, Fornecker LM, Chinot O, Peyrade F, Bouabdallah R, Moluçon-Chabrot C, Gyan E, Chauchet A, Casasnovas O, Oberic L, Delwail V, Abraham J, Roland V, Waultier-Rascalou A, Willems L, Morschhauser F, Fabbro M, Ursu R, Thieblemont C, Jardin F, Tempescul A, Malaise D, Touitou V, Nichelli L, Le Garff-Tavernier M, Plessier A, Bourget P, Bonmati C, Wantz-Mézières S, Giordan Q, Dorvaux V, Charron C, Jabeur W, Hoang-Xuan K, Taillandier L, and Soussain C
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Busulfan, Carmustine therapeutic use, Central Nervous System pathology, Cyclophosphamide therapeutic use, Etoposide, Humans, Neoplasm Recurrence, Local drug therapy, Prospective Studies, Thiotepa, Transplantation, Autologous, Treatment Outcome, Central Nervous System Neoplasms drug therapy, Central Nervous System Neoplasms pathology, Hematopoietic Stem Cell Transplantation adverse effects, Lymphoma drug therapy
- Abstract
We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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97. Genomic analysis of paired IDHwt glioblastomas reveals recurrent alterations of MPDZ at relapse after radiotherapy and chemotherapy.
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Chanez B, Appay R, Guille A, Lagarde A, Colin C, Adelaide J, Denicolai E, Jiguet-Jiglaire C, Bequet C, Graillon T, Boissonneau S, Nanni-Metellus I, Dufour H, Figarella-Branger D, Chinot O, and Tabouret E
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- Humans, Membrane Proteins, Middle Aged, RNA, Messenger, Recurrence, Brain Neoplasms drug therapy, Brain Neoplasms genetics, Brain Neoplasms radiotherapy, Glioblastoma drug therapy, Glioblastoma genetics, Glioblastoma radiotherapy, Glioma genetics
- Abstract
Purpose: We aimed to identify genomic drivers of glioblastoma inevitable recurrence., Methods: Ten pairs of initial and recurrent frozen IDHwt glioblastoma samples were screened by CGH Array. Next Generation Sequencing (NGS) was then performed on an enriched cohort of 19 pairs. MPDZ alterations were analyzed using TCGA dataset., Results: Nineteen IDHwt glioblastoma patients were included. Median age was 54.5 y/o (37.2-72.8). Using CGH array, unsupervised analysis aggregated the cohort by paired initial and recurrent tumors. Only 44% of CGH Array alterations were conserved at recurrence (amplifications: 55%; deletions: 30%). Two regions (including FPR1, 2 and 3) were lost at relapse: 19q13.33 and 19q13.41. MPDZ and 25 other genes were altered in ≥20% of recurrent tumors. NGS analysis of 29 candidate genes revealed 4 genes with pathogenic mutations: (FPR2, REL, TYRP1 and MPDZ). MPDZ (Multiple PDZ Domain Crumbs Cell Polarity Complex Component) was altered by two pathogenic mutations occurring at relapse. Using TCGA dataset we observed that a lower MPDZ mRNA expression was associated with IDHwt (p < 0.001) and grade IV (p < 0.001) gliomas. Finally, a low mRNA MPDZ expression was significantly correlated to poor overall survival in both IDHwt and IDH mutated gliomas, reinforcing the potential pejorative impact of MPDZ loss., Conclusion: Our results suggest that MPDZ is more frequently altered at relapse after radio-chemotherapy in glioblastoma IDHwt patients, suggesting that MPDZ impairment could contribute to the systematic resistance of these tumors opening new therapeutic perspectives., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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98. Characteristics of Anaplastic Oligodendrogliomas Short-Term Survivors: A POLA Network Study.
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Garnier L, Vidal C, Chinot O, Cohen-Jonathan Moyal E, Djelad A, Bronnimann C, Bekaert L, Taillandier L, Frenel JS, Langlois O, Colin P, Menei P, Dhermain F, Carpentier C, Gerazime A, Curtit E, Figarella-Branger D, Dehais C, and Ducray F
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- Chromosome Aberrations, Humans, Retrospective Studies, Survivors, Temozolomide therapeutic use, Brain Neoplasms pathology, Oligodendroglioma genetics
- Abstract
Background: Anaplastic oligodendrogliomas IDH-mutant and 1p/19q codeleted (AO) occasionally have a poor outcome. Herein we aimed at analyzing their characteristics., Methods: We retrospectively analyzed the characteristics of 44 AO patients with a cancer-specific survival <5 years (short-term survivors, STS) and compared them with those of 146 AO patients with a survival ≥5 years (classical survivors, CS) included in the POLA network., Results: Compared to CS, STS were older (P = .0001), less frequently presented with isolated seizures (P < .0001), more frequently presented with cognitive dysfunction (P < .0001), had larger tumors (P = .= .003), a higher proliferative index (P = .= .0003), and a higher number of chromosomal arm abnormalities (P = .= .02). Regarding treatment, STS less frequently underwent a surgical resection than CS (P = .= .0001) and were more frequently treated with chemotherapy alone (P = .= .009) or with radiotherapy plus temozolomide (P = .= .05). Characteristics independently associated with STS in multivariate analysis were cognitive dysfunction, a number of mitosis > 8, and the absence of tumor resection. Based on cognitive dysfunction, type of surgery, and number of mitosis, patients could be classified into groups of standard (18%) and high (62%) risk of <5 year survival., Conclusion: The present study suggests that although STS poor outcome appears to largely result from a more advanced disease at diagnosis, surgical resection may be particularly important in this population., (© The Author(s) 2022. Published by Oxford University Press.)
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- 2022
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99. Author Correction: EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood.
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Weller M, van den Bent M, Preusser M, Le Rhun E, Tonn JC, Minniti G, Bendszus M, Balana C, Chinot O, Dirven L, French P, Hegi ME, Jakola AS, Platten M, Roth P, Rudà R, Short S, Smits M, Taphoorn MJB, von Deimling A, Westphal M, Soffietti R, Reifenberger G, and Wick W
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- 2022
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100. [Development of advanced practice nursing in oncology and hematology-oncology in France: Early status report].
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Evans CK, Sabatier R, Chinot O, Loschi A, Arnaud S, and Mellinas M
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- Employment statistics & numerical data, France, Humans, Nursing Process statistics & numerical data, Hematology education, Hematology organization & administration, Hematology statistics & numerical data, Nursing Staff supply & distribution, Oncology Nursing education, Oncology Nursing organization & administration, Oncology Nursing statistics & numerical data, Surveys and Questionnaires statistics & numerical data
- Abstract
Background: Advanced practice nursing was introduced in France in 2018, in response to health needs. The first advanced practice nurses were graduated since 2019 and were trained in one among four medical areas including oncology and onco-hematology. The purpose of this article is to make an early assessment of the development of the profession of oncology Advanced Practice Nurse in France., Method: An exploratory study was conducted. A sample of 44 onco-hematology IPA graduated in 2019 and 2020 was recruited from June 2021 to end of July 2021. The 44 participants completed a questionnaire, by phone interviews or self-administered., Results and Conclusion: The distribution of the 44 participants concerns 12 of the 13 regions of metropolitan France. This profession shows an employability for 86% of the first graduates. These professionals practice in health care institutions and rather in oncology, 71% in the framework of an organizational protocol established with the oncologist. They appear to be well accepted by patients and oncology teams. Further studies on performance and quality indicators will make it possible to evaluate the added value of the oncology Advanced Practice Nurses in the cancer patient's pathway., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
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- 2022
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