Thomas Graillon1, Loic Ferrer2, Jason Siffre2, Marc Sanson3, Matthieu Peyre4, Hadrien Peyrière5, Grégory Mougel6, Didier Autran7, Emeline Tabouret7, Dominique Figarella-Branger8, Anne Barlier6, Michel Kalamarides4, Henry Dufour1, Thierry Colin2, Olivier Chinot7. 1. Aix Marseille Univ, APHM, INSERM, MMG, Department of Neursurgery, Hospital La Timone, Marseille, France. 2. SOPHiA GENETICS, Radiomics R&D Department, Cité de la Photonique, Pessac, France. 3. Neuro-Oncology Department, Hôpital La Pitié-Salpêtrière, Paris, France. 4. Neurosurgery Department, Hôpital La Pitié-Salpêtrière, Paris, France. 5. Neurosurgery Department, Hôpital La Timone, Marseille, France. 6. Aix Marseille Univ, APHM, INSERM, MMG Molecular Biology Department, Hôpital La Conception, Marseille, France. 7. Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, Neuro-Oncology Department, Hôpital La Timone, Marseille, France. 8. Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, Neuropathology department, Hôpital La Timone, Marseille, France.
Abstract
BACKGROUND: We aimed to improve the assessment of the drug activity in meningioma clinical trials based on the study of the 3D volume growth rate (3DVGR) in a series of aggressive meningiomas. We secondarily aimed to correlate 3DVGR study with patient outcome. METHODS: We performed a post hoc analysis based on volume data and 3DVGR extracted from CEVOREM study including 18 patients with 32 recurrent high-grade meningiomas and treated with everolimus and octreotide. The joint latent class model was used to classify tumor 3DVGR undertreatment. RESULTS: Class 1 includes lesions responding to treatment with decrease in volume in the first 3 months, and then a stabilization thereafter (9.5% of tumors) (mean pretreatment 3DVGR = 6.13%/month; mean undertreatment 3DVGR = -18.7%/month within 3 first months and -0.14%/month after the 3 first months). Class 2 includes lesions considered as stable or with a slight increase in volume undertreatment (65.5%) (mean pretreatment 3DVGR = 6.09%/month; undertreatment 3DVGR = -0.09% within the first 3 months). Class 3 includes lesions without 3DVGR decrease (25%) (mean pretreatment 3DVGR = 46.9%/month; mean undertreatment 3DVGR = 19.2%/month within the first 3 months). Patients with class 3 lesions had a significantly worse progression-free survival (PFS) rate than class 1 and 2 ones. CONCLUSIONS: Tumor 3DVGR could be helpful to detect early signal of drugs antitumoral activity or nonactivity. This volume response classification could help in the assessment of drug activity in tumors with mostly volume stabilization and rare response as aggressive meningiomas even with a low number of patients in complement to 6 months PFS.
BACKGROUND: We aimed to improve the assessment of the drug activity in meningioma clinical trials based on the study of the 3D volume growth rate (3DVGR) in a series of aggressive meningiomas. We secondarily aimed to correlate 3DVGR study with patient outcome. METHODS: We performed a post hoc analysis based on volume data and 3DVGR extracted from CEVOREM study including 18 patients with 32 recurrent high-grade meningiomas and treated with everolimus and octreotide. The joint latent class model was used to classify tumor 3DVGR undertreatment. RESULTS: Class 1 includes lesions responding to treatment with decrease in volume in the first 3 months, and then a stabilization thereafter (9.5% of tumors) (mean pretreatment 3DVGR = 6.13%/month; mean undertreatment 3DVGR = -18.7%/month within 3 first months and -0.14%/month after the 3 first months). Class 2 includes lesions considered as stable or with a slight increase in volume undertreatment (65.5%) (mean pretreatment 3DVGR = 6.09%/month; undertreatment 3DVGR = -0.09% within the first 3 months). Class 3 includes lesions without 3DVGR decrease (25%) (mean pretreatment 3DVGR = 46.9%/month; mean undertreatment 3DVGR = 19.2%/month within the first 3 months). Patients with class 3 lesions had a significantly worse progression-free survival (PFS) rate than class 1 and 2 ones. CONCLUSIONS: Tumor 3DVGR could be helpful to detect early signal of drugs antitumoral activity or nonactivity. This volume response classification could help in the assessment of drug activity in tumors with mostly volume stabilization and rare response as aggressive meningiomas even with a low number of patients in complement to 6 months PFS.
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