Tackling ALT-positive neuroblastoma: is it time to redefine risk classification systems? A systematic review with IPD meta-analysis
Background: The heterogeneous prognosis in neuroblastoma, shaped by telomere maintenance mechanisms (TMMs), notably the alternative lengthening of telomeres (ALT) pathway, necessitates a refined risk classification for high-risk patients. Current systems often lack precision, hindering tailored trea...
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Elsevier
2025-02-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558624001477 |
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| author | Marta Avinent-Pérez Frank Westermann Samuel Navarro Amparo López-Carrasco Rosa Noguera |
| author_facet | Marta Avinent-Pérez Frank Westermann Samuel Navarro Amparo López-Carrasco Rosa Noguera |
| author_sort | Marta Avinent-Pérez |
| collection | DOAJ |
| description | Background: The heterogeneous prognosis in neuroblastoma, shaped by telomere maintenance mechanisms (TMMs), notably the alternative lengthening of telomeres (ALT) pathway, necessitates a refined risk classification for high-risk patients. Current systems often lack precision, hindering tailored treatment approaches. This individual participant data (IPD) meta-analysis of survival among ALT-positive patients aims to improve risk classification systems, enhancing therapeutic strategies and patient outcomes. Methods: Following PRISMA-IPD guidelines, we conducted a comprehensive review of neuroblastoma patients retrieved from PubMed, Scopus, and Embase databases until March-2024. Patients were stratified into ALT-positive and TMM-negative subgroups. Overall and event-free survival probabilities were evaluated. Results: In our cohort of 293 patients (156 ALT-positive, 137 TMM-negative) obtained from eight different studies, ALT-positive individuals displayed lower survival rates than TMM-negative patients. Non-stage 4 ALT-positive patients had reduced overall and event-free survival probabilities compared to their TMM-negative counterparts, indicating potential misclassification. Stage 4 ALT-positive patients similarly showed poorer survival outcomes than non-stage 4 TMM-negative patients, underscoring the significance of ALT in patient prognosis. Conclusions: Our study highlights poorer outcomes in ALT-positive neuroblastoma patients, emphasizing the need to integrate TMM status into international risk classification guidelines. Standardizing TMM assessment is key for refining treatment strategies, considering the unique biology of ALT-positive patients. |
| format | Article |
| id | doaj-art-c61f1b75c99b49edbaa43fc6ebc57929 |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-c61f1b75c99b49edbaa43fc6ebc579292025-02-03T04:16:33ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-02-0160101106Tackling ALT-positive neuroblastoma: is it time to redefine risk classification systems? A systematic review with IPD meta-analysisMarta Avinent-Pérez0Frank Westermann1Samuel Navarro2Amparo López-Carrasco3Rosa Noguera4Department of Pathology, Medical School, University of Valencia, 46010 Valencia, Spain; Neuroblastoma Genomics, German Cancer Research Center (DKFZ), Heidelberg, GermanyNeuroblastoma Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp Children's Cancer Center (KiTZ), Heidelberg, GermanyDepartment of Pathology, Medical School, University of Valencia, 46010 Valencia, Spain; Incliva biomedical health research institute, 46010 Valencia, Spain; CIBER of Cancer (CIBERONC), 28029 Madrid, SpainDepartment of Pathology, Medical School, University of Valencia, 46010 Valencia, Spain; Incliva biomedical health research institute, 46010 Valencia, Spain; CIBER of Cancer (CIBERONC), 28029 Madrid, Spain; Corresponding authors.Department of Pathology, Medical School, University of Valencia, 46010 Valencia, Spain; Incliva biomedical health research institute, 46010 Valencia, Spain; CIBER of Cancer (CIBERONC), 28029 Madrid, Spain; Corresponding authors.Background: The heterogeneous prognosis in neuroblastoma, shaped by telomere maintenance mechanisms (TMMs), notably the alternative lengthening of telomeres (ALT) pathway, necessitates a refined risk classification for high-risk patients. Current systems often lack precision, hindering tailored treatment approaches. This individual participant data (IPD) meta-analysis of survival among ALT-positive patients aims to improve risk classification systems, enhancing therapeutic strategies and patient outcomes. Methods: Following PRISMA-IPD guidelines, we conducted a comprehensive review of neuroblastoma patients retrieved from PubMed, Scopus, and Embase databases until March-2024. Patients were stratified into ALT-positive and TMM-negative subgroups. Overall and event-free survival probabilities were evaluated. Results: In our cohort of 293 patients (156 ALT-positive, 137 TMM-negative) obtained from eight different studies, ALT-positive individuals displayed lower survival rates than TMM-negative patients. Non-stage 4 ALT-positive patients had reduced overall and event-free survival probabilities compared to their TMM-negative counterparts, indicating potential misclassification. Stage 4 ALT-positive patients similarly showed poorer survival outcomes than non-stage 4 TMM-negative patients, underscoring the significance of ALT in patient prognosis. Conclusions: Our study highlights poorer outcomes in ALT-positive neuroblastoma patients, emphasizing the need to integrate TMM status into international risk classification guidelines. Standardizing TMM assessment is key for refining treatment strategies, considering the unique biology of ALT-positive patients.http://www.sciencedirect.com/science/article/pii/S1476558624001477Telomere maintenance mechanismsChildhood cancerPrognosis biomarkerTherapeutic strategiesSurvival |
| spellingShingle | Marta Avinent-Pérez Frank Westermann Samuel Navarro Amparo López-Carrasco Rosa Noguera Tackling ALT-positive neuroblastoma: is it time to redefine risk classification systems? A systematic review with IPD meta-analysis Neoplasia: An International Journal for Oncology Research Telomere maintenance mechanisms Childhood cancer Prognosis biomarker Therapeutic strategies Survival |
| title | Tackling ALT-positive neuroblastoma: is it time to redefine risk classification systems? A systematic review with IPD meta-analysis |
| title_full | Tackling ALT-positive neuroblastoma: is it time to redefine risk classification systems? A systematic review with IPD meta-analysis |
| title_fullStr | Tackling ALT-positive neuroblastoma: is it time to redefine risk classification systems? A systematic review with IPD meta-analysis |
| title_full_unstemmed | Tackling ALT-positive neuroblastoma: is it time to redefine risk classification systems? A systematic review with IPD meta-analysis |
| title_short | Tackling ALT-positive neuroblastoma: is it time to redefine risk classification systems? A systematic review with IPD meta-analysis |
| title_sort | tackling alt positive neuroblastoma is it time to redefine risk classification systems a systematic review with ipd meta analysis |
| topic | Telomere maintenance mechanisms Childhood cancer Prognosis biomarker Therapeutic strategies Survival |
| url | http://www.sciencedirect.com/science/article/pii/S1476558624001477 |
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