The clinical significance of sub-total surgical resection in childhood medulloblastoma: a multi-cohort analysis of 1100 patientsResearch in context
Summary: Background: Medulloblastoma patients with a sub-total surgical resection (STR; >1.5 cm2 primary tumour residuum post-surgery) typically receive intensified treatment. However, the association of STR with poor outcomes has not been observed consistently, questioning the validity of STR a...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | EClinicalMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537024000488 |
| _version_ | 1827349845240709120 |
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| author | Claire Keeling Simon Davies Jack Goddard Vijay Ramaswamy Edward C. Schwalbe Simon Bailey Debbie Hicks Steven C. Clifford |
| author_facet | Claire Keeling Simon Davies Jack Goddard Vijay Ramaswamy Edward C. Schwalbe Simon Bailey Debbie Hicks Steven C. Clifford |
| author_sort | Claire Keeling |
| collection | DOAJ |
| description | Summary: Background: Medulloblastoma patients with a sub-total surgical resection (STR; >1.5 cm2 primary tumour residuum post-surgery) typically receive intensified treatment. However, the association of STR with poor outcomes has not been observed consistently, questioning the validity of STR as a high-risk disease feature. Methods: We collected extent of resection (EOR) data from 1110 patients (from UK CCLG centres (n = 416, collected between September 1990 and July 2014) and published (n = 694) cohorts), the largest cohort of molecularly and clinically annotated tumours assembled to specifically assess the significance of EOR. We performed association and univariable/multivariable survival analyses, assessing overall survival (OS) cohort-wide and with reference to the four consensus medulloblastoma molecular groups and clinical features. Findings: STR was reported in 20% (226/1110) of patients. Non-WNT (p = 0.047), children <5 years at diagnosis (p = 0.021) and metastatic patients (p < 0.0001) were significantly more likely to have a STR. In cohort-wide analysis, STR was associated with worse survival in univariable analysis (p < 0.0001). Examination of specific disease contexts showed that STR was prognostic in univariate analysis for patients receiving cranio-spinal irradiation (CSI) and chemotherapy (p = 0.016) and for patients with Group 3 tumours receiving CSI (p = 0.039). STR was not independently prognostic in multivariable analyses; outcomes for patients who have STR as their only risk-feature are as per standard-risk disease. Specifically, STR was not prognostic in non-metastatic patients that received upfront CSI. Interpretation: In a cohort of 1100 molecularly characterised medulloblastoma patients, STR (n = 226) predicted significantly lower OS in univariable analysis, but was not an independent prognostic factor. Our data suggest that maximal safe resection can continue to be carried out for patients with medulloblastoma and suggest STR should not inform patient management when observed as a sole, isolated risk-feature. Funding: Cancer Research UK, Newcastle Hospitals Charity, Children’s Cancer North, British Division of the International Academy of Pathology. |
| first_indexed | 2024-03-08T00:49:11Z |
| format | Article |
| id | doaj.art-8aac62da82144c32925d2195f0158088 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-03-08T00:49:11Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-8aac62da82144c32925d2195f01580882024-02-15T05:25:07ZengElsevierEClinicalMedicine2589-53702024-03-0169102469The clinical significance of sub-total surgical resection in childhood medulloblastoma: a multi-cohort analysis of 1100 patientsResearch in contextClaire Keeling0Simon Davies1Jack Goddard2Vijay Ramaswamy3Edward C. Schwalbe4Simon Bailey5Debbie Hicks6Steven C. Clifford7Wolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle upon Tyne, United KingdomWolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle upon Tyne, United KingdomWolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle upon Tyne, United KingdomNeuro-oncology Section, Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, CanadaWolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom; Department of Applied Sciences, Northumbria University, Newcastle upon Tyne, United KingdomWolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom; Great North Children's Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United KingdomWolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom; Corresponding author. Wolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.Wolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom; Corresponding author. Wolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.Summary: Background: Medulloblastoma patients with a sub-total surgical resection (STR; >1.5 cm2 primary tumour residuum post-surgery) typically receive intensified treatment. However, the association of STR with poor outcomes has not been observed consistently, questioning the validity of STR as a high-risk disease feature. Methods: We collected extent of resection (EOR) data from 1110 patients (from UK CCLG centres (n = 416, collected between September 1990 and July 2014) and published (n = 694) cohorts), the largest cohort of molecularly and clinically annotated tumours assembled to specifically assess the significance of EOR. We performed association and univariable/multivariable survival analyses, assessing overall survival (OS) cohort-wide and with reference to the four consensus medulloblastoma molecular groups and clinical features. Findings: STR was reported in 20% (226/1110) of patients. Non-WNT (p = 0.047), children <5 years at diagnosis (p = 0.021) and metastatic patients (p < 0.0001) were significantly more likely to have a STR. In cohort-wide analysis, STR was associated with worse survival in univariable analysis (p < 0.0001). Examination of specific disease contexts showed that STR was prognostic in univariate analysis for patients receiving cranio-spinal irradiation (CSI) and chemotherapy (p = 0.016) and for patients with Group 3 tumours receiving CSI (p = 0.039). STR was not independently prognostic in multivariable analyses; outcomes for patients who have STR as their only risk-feature are as per standard-risk disease. Specifically, STR was not prognostic in non-metastatic patients that received upfront CSI. Interpretation: In a cohort of 1100 molecularly characterised medulloblastoma patients, STR (n = 226) predicted significantly lower OS in univariable analysis, but was not an independent prognostic factor. Our data suggest that maximal safe resection can continue to be carried out for patients with medulloblastoma and suggest STR should not inform patient management when observed as a sole, isolated risk-feature. Funding: Cancer Research UK, Newcastle Hospitals Charity, Children’s Cancer North, British Division of the International Academy of Pathology.http://www.sciencedirect.com/science/article/pii/S2589537024000488Paediatric oncologySurgical resectionPrognosisMolecular groups |
| spellingShingle | Claire Keeling Simon Davies Jack Goddard Vijay Ramaswamy Edward C. Schwalbe Simon Bailey Debbie Hicks Steven C. Clifford The clinical significance of sub-total surgical resection in childhood medulloblastoma: a multi-cohort analysis of 1100 patientsResearch in context EClinicalMedicine Paediatric oncology Surgical resection Prognosis Molecular groups |
| title | The clinical significance of sub-total surgical resection in childhood medulloblastoma: a multi-cohort analysis of 1100 patientsResearch in context |
| title_full | The clinical significance of sub-total surgical resection in childhood medulloblastoma: a multi-cohort analysis of 1100 patientsResearch in context |
| title_fullStr | The clinical significance of sub-total surgical resection in childhood medulloblastoma: a multi-cohort analysis of 1100 patientsResearch in context |
| title_full_unstemmed | The clinical significance of sub-total surgical resection in childhood medulloblastoma: a multi-cohort analysis of 1100 patientsResearch in context |
| title_short | The clinical significance of sub-total surgical resection in childhood medulloblastoma: a multi-cohort analysis of 1100 patientsResearch in context |
| title_sort | clinical significance of sub total surgical resection in childhood medulloblastoma a multi cohort analysis of 1100 patientsresearch in context |
| topic | Paediatric oncology Surgical resection Prognosis Molecular groups |
| url | http://www.sciencedirect.com/science/article/pii/S2589537024000488 |
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