Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2022-09-01
|
| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359221113693 |
| _version_ | 1828408587910643712 |
|---|---|
| author | Giada Del Baldo Andrea Carai Rachid Abbas Antonella Cacchione Mara Vinci Valentina Di Ruscio Giovanna Stefania Colafati Sabrina Rossi Francesca Diomedi Camassei Nicola Maestro Sara Temelso Giulia Pericoli Emmanuel De Billy Isabella Giovannoni Alessia Carboni Martina Rinelli Emanuele Agolini Alan Mackay Chris Jones Silvia Chiesa Mario Balducci Franco Locatelli Angela Mastronuzzi |
| author_facet | Giada Del Baldo Andrea Carai Rachid Abbas Antonella Cacchione Mara Vinci Valentina Di Ruscio Giovanna Stefania Colafati Sabrina Rossi Francesca Diomedi Camassei Nicola Maestro Sara Temelso Giulia Pericoli Emmanuel De Billy Isabella Giovannoni Alessia Carboni Martina Rinelli Emanuele Agolini Alan Mackay Chris Jones Silvia Chiesa Mario Balducci Franco Locatelli Angela Mastronuzzi |
| author_sort | Giada Del Baldo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T11:41:58Z |
| format | Article |
| id | doaj.art-6424a769c3b241c4b0d3dc614eda6a04 |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-12-10T11:41:58Z |
| publishDate | 2022-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-6424a769c3b241c4b0d3dc614eda6a042022-12-22T01:50:13ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592022-09-011410.1177/17588359221113693Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experienceGiada Del BaldoAndrea CaraiRachid AbbasAntonella CacchioneMara VinciValentina Di RuscioGiovanna Stefania ColafatiSabrina RossiFrancesca Diomedi CamasseiNicola MaestroSara TemelsoGiulia PericoliEmmanuel De BillyIsabella GiovannoniAlessia CarboniMartina RinelliEmanuele AgoliniAlan MackayChris JonesSilvia ChiesaMario BalducciFranco LocatelliAngela MastronuzziBackground: 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.https://doi.org/10.1177/17588359221113693 |
| spellingShingle | Giada Del Baldo Andrea Carai Rachid Abbas Antonella Cacchione Mara Vinci Valentina Di Ruscio Giovanna Stefania Colafati Sabrina Rossi Francesca Diomedi Camassei Nicola Maestro Sara Temelso Giulia Pericoli Emmanuel De Billy Isabella Giovannoni Alessia Carboni Martina Rinelli Emanuele Agolini Alan Mackay Chris Jones Silvia Chiesa Mario Balducci Franco Locatelli Angela Mastronuzzi Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience Therapeutic Advances in Medical Oncology |
| title | Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience |
| title_full | Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience |
| title_fullStr | Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience |
| title_full_unstemmed | Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience |
| title_short | Targeted therapy for pediatric diffuse intrinsic pontine glioma: a single-center experience |
| title_sort | targeted therapy for pediatric diffuse intrinsic pontine glioma a single center experience |
| url | https://doi.org/10.1177/17588359221113693 |
| work_keys_str_mv | AT giadadelbaldo targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT andreacarai targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT rachidabbas targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT antonellacacchione targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT maravinci targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT valentinadiruscio targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT giovannastefaniacolafati targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT sabrinarossi targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT francescadiomedicamassei targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT nicolamaestro targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT saratemelso targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT giuliapericoli targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT emmanueldebilly targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT isabellagiovannoni targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT alessiacarboni targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT martinarinelli targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT emanueleagolini targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT alanmackay targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT chrisjones targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT silviachiesa targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT mariobalducci targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT francolocatelli targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience AT angelamastronuzzi targetedtherapyforpediatricdiffuseintrinsicpontinegliomaasinglecenterexperience |