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Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial.
Capoluongo, E D; Pellegrino, B; Arenare, L; Califano, D; Scambia, G; Beltrame, L; Serra, V; Scaglione, G L; Spina, A; Cecere, S C; De Cecio, R; Normanno, N; Colombo, N; Lorusso, D; Russo, D; Nardelli, C; D'Incalci, M; Llop-Guevara, A; Pisano, C; Baldassarre, G; Mezzanzanica, D; Artioli, G; Setaro, M; Tasca, G; Roma, C; Campanini, N; Cinieri, S; Sergi, A; Musolino, A; Perrone, F; Chiodini, P; Marchini, S; Pignata, S.
Afiliación
  • Capoluongo ED; Department of Molecular Medicine and Medical Biotechnology, Università degli Studi di Napoli Federico II, Naples; Azienda Ospedaliera per L'Emergenza, Cannizzaro, Catania.
  • Pellegrino B; Department of Medicine and Surgery, University of Parma, Parma; Medical Oncology and Breast Unit, University Hospital of Parma, Parma; Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC), Parma.
  • Arenare L; Clinical Trial Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Naples.
  • Califano D; Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Naples.
  • Scambia G; Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome; Department of Life Science and Public Health, Catholic University of Sacred Heart Largo Agostino Gemelli, Rome.
  • Beltrame L; Molecular Pharmacology laboratory., Group of Cancer Pharmacology IRCCS Humanitas Research Hospital, Rozzano, Italy.
  • Serra V; Vall d'Hebron Institute of Oncology, Barcelona, Spain.
  • Scaglione GL; Advanced Biotechnology, Università Federico II-CEINGE, Naples; IDI-IRCSS, Rome.
  • Spina A; Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Naples.
  • Cecere SC; Uro-Gynecologic Oncology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples.
  • De Cecio R; Pathology Unit, Istituto Nazionale Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli.
  • Normanno N; Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli.
  • Colombo N; University of Milan-Bicocca and European Institute of Oncology IRCCS, Milan.
  • Lorusso D; Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome; Department of Life Science and Public Health, Catholic University of Sacred Heart Largo Agostino Gemelli, Rome.
  • Russo D; Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Naples.
  • Nardelli C; Department of Molecular Medicine and Medical Biotechnology, Università degli Studi di Napoli Federico II, Naples; Advanced Biotechnology, Università Federico II-CEINGE, Naples.
  • D'Incalci M; Molecular Pharmacology laboratory., Group of Cancer Pharmacology IRCCS Humanitas Research Hospital, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan.
  • Llop-Guevara A; Vall d'Hebron Institute of Oncology, Barcelona, Spain.
  • Pisano C; Uro-Gynecologic Oncology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples.
  • Baldassarre G; Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, Aviano.
  • Mezzanzanica D; Molecular Therapies Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
  • Artioli G; Oncologia Medica, ULSS2 Marca Trevigiana, Treviso.
  • Setaro M; Advanced Biotechnology, Università Federico II-CEINGE, Naples.
  • Tasca G; Division of Oncology 2, Istituto Oncologico Veneto IRCCS, Padova.
  • Roma C; Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori 'Fondazione Giovanni Pascale', IRCCS, Napoli.
  • Campanini N; Unit of Pathological Anatomy, Department of Medicine and Surgery, University Hospital of Parma, Parma.
  • Cinieri S; Oncologia Medica, Ospedale Senatore Antonio Perrino, Brindisi.
  • Sergi A; Molecular Pharmacology laboratory., Group of Cancer Pharmacology IRCCS Humanitas Research Hospital, Rozzano, Italy; Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan.
  • Musolino A; Department of Medicine and Surgery, University of Parma, Parma; Medical Oncology and Breast Unit, University Hospital of Parma, Parma; Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC), Parma.
  • Perrone F; Clinical Trial Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Naples.
  • Chiodini P; Department of Mental Health and Public Medicine, Section of Statistics, Università degli Studi della Campania Luigi Vanvitelli, Napoli, Italy.
  • Marchini S; Molecular Pharmacology laboratory., Group of Cancer Pharmacology IRCCS Humanitas Research Hospital, Rozzano, Italy.
  • Pignata S; Uro-Gynecologic Oncology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples. Electronic address: s.pignata@istitutotumori.na.it.
ESMO Open ; 7(5): 100585, 2022 10.
Article en En | MEDLINE | ID: mdl-36156447
BACKGROUND: The detection of homologous recombination deficiency (HRD) can identify patients who are more responsive to platinum and poly ADP ribose polymerase inhibitors (PARPi). MyChoice CDx (Myriad) is the most used HRD test in ovarian cancer (OC). However, some limitations of commercial tests exist, because of the high rate of inconclusive results, costs, and the impossibility of evaluating functional resistance mechanisms. PATIENTS AND METHODS: Two academic genomic tests and a functional assay, the RAD51 foci, were evaluated to detect HRD. One hundred patients with high-grade OC enrolled in the MITO16A/MaNGO-OV2 trial and treated with first-line therapy with carboplatin, paclitaxel, and bevacizumab were analyzed. RESULTS: The failure rate of the two genomic assays was 2%. The sensitivity in detecting HRD when compared with Myriad was 98.1% and 90.6%, respectively. The agreement rate with Myriad was 0.92 and 0.87, with a Cohen's κ coefficient corresponding to 0.84 and 0.74, respectively. For the RAD51 foci assay, the failure rate was 30%. When the test was successful, discordant results for deficient and proficient tumors were observed, and additional HRD patients were identified compared to Myriad; sensitivity was 82.9%, agreement rate was 0.65, and Cohen's κ coefficient was 0.18. The HRD detected by genomic assays and residual tumor at primary surgery and stage was correlated with progression-free survival at multivariate analysis. CONCLUSIONS: Results suggest the feasibility of academic tests for assessing HRD status that show robust concordance with Myriad and correlation with clinical outcome. The contribution of the functional information related to the RAD51 foci test to the genomic data needs further investigation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Mangifera Límite: Female / Humans Idioma: En Revista: ESMO Open Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Mangifera Límite: Female / Humans Idioma: En Revista: ESMO Open Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido