Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience.

Autor:	Del Baldo G; Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Carai A; Neurosurgery Unit, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy., Abbas R; CESP, INSERM, Université Paris Sud, Villejuif, France., Cacchione A; Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Vinci M; Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Di Ruscio V; Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Colafati GS; Oncological Neuroradiology Unit, Imaging Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Rossi S; Pathology Unit, Department of Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Diomedi Camassei F; Pathology Unit, Department of Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Maestro N; Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Temelso S; Division of Molecular Pathology, The Institute of Cancer Research, London, UK.; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK., Pericoli G; Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., De Billy E; Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Giovannoni I; Pathology Unit, Department of Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Carboni A; Oncological Neuroradiology Unit, Imaging Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Rinelli M; Laboratory of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Agolini E; Laboratory of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Mackay A; Division of Molecular Pathology, The Institute of Cancer Research, London, UK.; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK., Jones C; Division of Molecular Pathology, The Institute of Cancer Research, London, UK.; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK., Chiesa S; Department of Radiotherapy, Fondazione Policlinico Universitario 'A. Gemelli,' Catholic University of Sacred Heart, Rome, Italy., Balducci M; Department of Radiotherapy, Fondazione Policlinico Universitario 'A. Gemelli,' Catholic University of Sacred Heart, Rome, Italy., Locatelli F; Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.; Department of Life Sciences and Public Health, Fondazione Policlinico Universitario 'A. Gemelli,' Catholic University of Sacred Heart, Rome, Italy., Mastronuzzi A; Department of Pediatric Haematology and Oncology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in medical oncology [Ther Adv Med Oncol] 2022 Sep 06; Vol. 14, pp. 17588359221113693. Date of Electronic Publication: 2022 Sep 06 (Print Publication: 2022).
DOI:	10.1177/17588359221113693
Abstrakt:	Background: Diffuse intrinsic pontine glioma (DIPG) is a fatal disease with a median overall survival (OS) of less than 12 months after diagnosis. Radiotherapy (RT) still remains the mainstay treatment. Several other therapeutic strategies have been attempted in the last years without a significant effect on OS. Although radiological imaging is the gold standard for DIPG diagnosis, the urgent need to improve the survival has led to the reconsideration of biopsy with the aim to better understand the molecular profile of DIPG and support personalized treatment. Methods: In this study, we present a single-center experience in treating DIPG patients at disease progression combining targeted therapies with standard of care. Biopsy was proposed to all patients at diagnosis or disease progression. First-line treatment included RT and nimotuzumab/vinorelbine or temozolomide. Immunohistochemistry-targeted research included study of mTOR/p-mTOR pathway and BRAFv600E . Molecular analyses included polymerase chain reaction, followed by Sanger sequences and/or next-generation sequencing. Results: Based on the molecular profile, targeted therapy was administered in 9 out of 25 patients, while the remaining 16 patients were treated with standard of care. Personalized treatment included inhibition of the PI3K/AKT/mTOR pathway (5/9), PI3K/AKT/mTOR pathway and BRAFv600E (1/9), ACVR1 (2/9) and PDGFRA (1/9); no severe side effects were reported during treatment. Response to treatment was evaluated according to Response Assessment in Pediatric Neuro-Oncology criteria, and the overall response rate within the cohort was 66%. Patients treated with targeted therapies were compared with the control cohort of 16 patients. Clinical and pathological characteristics of the two cohorts were homogeneous. Median OS in the personalized treatment and control cohort was 20.26 and 14.18 months, respectively ( p  = 0.032). In our experience, the treatment associated with the best OS was everolimus. Conclusion: Despite the small simple size of our study, our data suggest a prognostic advantage and a safe profile of targeted therapies in DIPG patients, and we strongly advocate to reconsider the role of biopsy for these patients. Competing Interests: Competing Interests: The authors declare that there is no conflict of interest. (© The Author(s), 2022.)
Databáze:	MEDLINE
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