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@ARTICLE{Karschnia:306605,
author = {P. Karschnia and J. S. Young and M. M. J. Wijnenga and T.
Sciortino and N. Teske and A. Corell and A. Wagner and G.
Youssef and Y. W. Park and L. Häni and S. T. Jünger and A.
Dono and F. Ehret$^*$ and E. E. M. Mireles and N. Neidert
and F. Bruno and C. A. Tuchek and T. van der Vaart and M.
Rossi and M. C. Nibali and L. Gay and A. Gramelt and N.
Tandon and S. S. Ahn and J. H. Chang and M. Weller and A. J.
P. E. Vincent and R. Goldbrunner and D. P. Cahill and R. Y.
Huang and A. Raabe and B. Meyer and J. Beck and A. M.
Molinaro and S. M. Chang and M. A. Vogelbaum and R. Rudà
and E. O. Vik-Mo and J. Dietrich and Y. Esquenazi and S. J.
Grau and P. Y. Wen and A. S. Jakola and O. Schnell and L.
Bello and M. J. van den Bent and S. Hervey-Jumper and M. S.
Berger and J.-C. Tonn},
title = {{A} prognostic classification system for extent of
resection in {IDH}-mutant grade 2 glioma: an international,
multicentre, retrospective cohort study with external
validation by the {RANO} resect group.},
journal = {The lancet / Oncology},
volume = {26},
number = {12},
issn = {1470-2045},
address = {London},
publisher = {The Lancet Publ. Group},
reportid = {DKFZ-2025-02642},
pages = {1638 - 1650},
year = {2025},
abstract = {The efficacy of resection in IDH-mutant grade 2 gliomas
remain controversial since terminology for the extent of
resection has been inconsistently applied across studies. We
aimed to establish a standardised classification for the
extent of resection and assess the association between
supramaximal resection and survival across molecular
subtypes.In this international, multicentre, retrospective
study, patients aged 18 years and older with newly diagnosed
grade 2 IDH-mutant glioma were identified from institutional
databases across 16 centres in the USA, Europe, and Asia
between between Sept 1, 1993, and May 10, 2024. We used Cox
proportional hazard regressions to analyse the associations
between residual tumour and progression-free survival and
overall survival. Patients were stratified according to a
previously postulated classification system based on
residual tumour volume. A cohort of patients from UCSF
diagnosed between Feb 16, 1998, and Nov 14, 2017, was used
for geographically and institutionally independent external
validation.We identified 1391 patients with newly diagnosed
IDH-mutant grade 2 gliomas, with a median follow-up of 81
months $(95\%$ CI 78-85). 728 patients (379 with astrocytoma
and 349 with oligodendroglioma) received no first-line
treatment beyond surgery, allowing us to study the isolated
effects of resection. Patients with maximal T2-fluid
attenuated inversion recovery (T2-FLAIR) resection (class 2;
0-5 cm3 remnant) had superior progression-free and overall
survival compared with submaximal T2-FLAIR resection (class
3; 5-25 cm3 remnant) or minimal T2-FLAIR resection (class 4;
>25 cm3 remnant), with 10-year survival rates of $82\%$
$(95\%$ CI 76-87) versus $75\%$ (62-84) versus $48\%$
(29-65; p<0·0001) and 5-year progression-free survival
rates of $44\%$ (38-50) versus $25\%$ (16-34) versus $12\%$
(4-24; p<0·0001), respectively. Resection beyond T2-FLAIR
borders (class 1) provided survival benefits, with a 10-year
survival rate of $98\%$ $(95\%$ CI 92-99) and a 5-year
progression-free survival rate of $83\%$ (76-88) for
supramaximal T2-FLAIR resection (class 1). Associations
between survival and extensive resection were evident after
3 years in astrocytomas, whereas survival curves separated
after 6-8 years in oligodendrogliomas. The prognostic
relevance of the four-tier classification was conserved in
multivariable analyses, in 625 patients receiving first-line
chemotherapy or radiotherapy (with or without chemotherapy),
and in the external UCSF cohort of 381 patients with
IDH-mutant grade 2 gliomas.The proposed RANO classification
for extent of resection could serve as a tool for prognostic
stratification. Although associations between survival and
extensive surgery are evident sooner in patients with
astrocytoma, supramaximal resection also translates into
survival benefits for patients with
oligodendrogliomas.None.},
keywords = {Humans / Middle Aged / Female / Isocitrate Dehydrogenase:
genetics / Male / Retrospective Studies / Adult / Brain
Neoplasms: surgery / Brain Neoplasms: genetics / Brain
Neoplasms: pathology / Brain Neoplasms: mortality / Brain
Neoplasms: classification / Mutation / Glioma: surgery /
Glioma: genetics / Glioma: pathology / Glioma: mortality /
Prognosis / Neoplasm Grading / Aged / Progression-Free
Survival / Young Adult / Neurosurgical Procedures: mortality
/ Neoplasm, Residual / Isocitrate Dehydrogenase (NLM
Chemicals) / IDH2 protein, human (NLM Chemicals)},
cin = {BE01},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41308678},
doi = {10.1016/S1470-2045(25)00534-0},
url = {https://inrepo02.dkfz.de/record/306605},
}