dans le cadre des programmes du SIRIC BRIO

Genomic index predicts clinical outcome of intermediate-risk gastrointestinal stromal tumours, providing a new inclusion criterion for imatinib adjuvant therapy.

Source : Eur J Cancer. 2014 Nov 6. pii: S0959-8049(14)01050-8. doi: 10.1016/j.ejca.2014.10.014. [Epub ahead of print]

Mots Clés :  Genomic index, Intermediate-GIST, Metastasis, Miettinen, Prognostic factor

Auteurs : Lartigue L, Neuville A, Lagarde P, Brulard C, Rutkowski P, Tos PD, Wardelmann E, Debiec-Rychter M, Italiano A, Coindre JM, Chibon F.

Résumé :
PURPOSE:
Imatinib mesylate is the front-line targeted therapy for gastrointestinal stromal tumours (GISTs). Patient’s eligibility to adjuvant imatinib after primary tumour resection is currently based on histological and clinical risk assessment. While therapeutic options are clear for the very-low, low and high-risk subpopulations, no standard is actually available for the tumours classified as intermediate. Since we recently validated genomic index (GI), a measure of the level of genomic alterations, as a strong predictor of clinical outcome in GIST, we asked whether it could also represent a novel prognostic factor for the intermediate subgroup.

EXPERIMENTAL DESIGN:
82 intermediate risk patients were selected based on the Armed Forces Institute of Pathology (AFIP) classification for genomic profiling.

RESULTS:
Data revealed that even if studied samples generally harboured a combination of the typical genetic aberrations found in GIST, i.e. 1p, 14q 22q deletions and frequently lost CDKN2A locus on chromosome 9, they profoundly differed from each other on the total number of genomic changes and GI value. Kaplan-Meier analyses of metastatic-free survival unveiled that stratification of the tumours by the GI value at a cutoff of 10 separated the good from the poor prognosis patients, proven that metastatic-risk in GIST intermediate patients is strongly associated with high GI values and genome complexity.

CONCLUSION:
GI is validated here as a robust marker to predict intermediate-GIST clinical outcome. Applicable in numerous Pathology Laboratories already using array comparative genomic hybridisation (CGH) with formalin-fixed paraffin-embedded (FFPE) samples, this assay presently stands as an efficient tool for the clinical management of intermediate GIST-patients.

Copyright © 2014 Elsevier Ltd. All rights reserved.

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The oct4 protein: more than a magic stemness marker. Am J Stem Cells, 3 (2), 74-82.

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Guidelines for time-to-event endpoint definitions in sarcomas and gastro-intestinal stromal tumors (GIST) trials. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)

Auteurs : Bellera CA, Penel N, Ouali M, Bonvalot S, Casalli PG, Nielsen OS, Delannes M, Litière S, Bonnetain F, Dabakuyo TS, Benjamin R, Blay JY, Bui BN, Collin F, Delaney TF, Duffaud F, Filleron T, Fiore M, Gelderblom H, George S, Grimer R, Grosclaude P, Gronchi A, Haas R, Hohenberger P, Issels R, Italiano A, Jooste V, Krarup-Hansen A, Le Péchoux C, Mussi C, Oberlin O, Patel S, Piperno-Neumann S, Raut C, Ray-Coquard I, Rutkowski P, Schuetze S, Sleijder S, Stoeckle E, Van Glabbeke M, Woll P, Gourgou-Bourgade S, Mathoulin-Pélissier S

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Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial.

Auteurs : Bonnefoi H, Litière S, Piccart M, Macgrogan G, Fumoleau P, Brain E, Petit T, Rouanet P, Jassem J, Moldovan C, Bodmer A, Zaman K, Cufer T, Campone M, Luporsi E, Malmström P, Werutsky G, Bogaerts J, Bergh J, Cameron DA; on behalf of the EORTC 10994/BIG 1-00 Study investigators.

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GDC-0449 in patients with advanced chondrosarcomas: a French Sarcoma Group/US and French National Cancer Institute single-arm phase II collaborative study. Ann Oncol 2013 ; 24 : 2922-6.

Auteurs : Italiano A1, Le Cesne A, Bellera C, Piperno-Neumann S, Duffaud F, Penel N, Cassier P, Domont J, Takebe N, Kind M, Coindre JM, Blay JY, Bui BN.

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From suboptimal to optimal treatment in older patients with cancer – J Geriatr Oncol 2013 ; 4 : 291-3.

Auteur : Soubeyran P.