Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group

Abstract

Background Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (I) explore the prognostic utility of the classification system and (II) define how much removed non-CE tumor translates into a survival benefit. Methods The international RANO resect group retrospectively searched previously compiled databases from seven neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and post-operative MRI were collected. Results We collected 1008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC 26981/22981 (TMZ/RT→TMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm 3) were favorably associated with outcome: patients with ‘maximal CE resection’ (class 2) had superior outcome compared to patients with ‘submaximal CE resection’ (class 3) or ‘biopsy’ (class 4). Extensive resection of non-CE tumor (≤5 cm 3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 (‘supramaximal CE resection’). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers. Conclusions The proposed “RANO categories for extent of resection in glioblastoma” are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such ‘supramaximal CE resection’.

TERTpromotor status does not add prognostic information inIDH-wildtype glioblastomas fulfilling other diagnostic WHO criteria: A report of the RANOresectgroup

“…With approval of the ethics committee of the Ludwig-Maximilians-University (Munich, Germany; AZ-21-0996), the RANO resect group compiled a retrospective database of newly diagnosed IDH -wildtype glioblastomas treated between 2003 and 2022 with a follow-up of ≥3 months. 5 For the current study, individuals were selected when information on TERT promotor mutation status was available for review. Demographics, molecular information, clinical data, and outcome were extracted; and date of progression was determined per RANO criteria.…”

Frequency and Prognostic Relevance of Volumetric MRI Changes in Contrast- and Non-Contrast-Enhancing Tumor Compartments between Surgery and Radiotherapy of IDHwt Glioblastoma

“…In most cases, no residual tumor volume was detected on immediate postoperative (postOP) MRI with median postoperative CE tumor volume 0.0 ± 0.4 cm 3 (range: 0–24 cm 3 ) and median postoperative non-CE T2-FLAIR lesion volume 0.0 ± 1.6 cm 3 (range: 0–64 cm 3 ). In detail, residual tumor volumes were allocated to their respective RANO resect classes for EOR in glioblastoma [ 3 ]. Here, supramaximal CE resection (class 1) was achieved in 36/64 patients (56%), maximal CE resection (class 2) was possible in 15/64 patients (23%), and the remaining 13/64 patients (20%) underwent submaximal CE resection (class 3; Figure 1 A).…”

“…For all patients, we routinely applied a macrocyclic gadolinium-based contrast agent (gadoteric acid, Dotagraf 0.5 mmol/mL; 0.2 mL/kg bodyweight; 0.1 mmol/kg; flow rate 1 mL/s). Volumetric image analyses were performed as previously described [ 3 ]. In short, tumor volumes were quantified by ceT1-weighted and FLAIR (or if not available, T2)-sequences on pre-/postoperative and pre-radiotherapy MRI scans using commercially available imaging software (BrainLab ® Elements; Munich, Germany).…”

“…Microsurgical resection represents the current standard of care when followed by adjuvant radiochemotherapy and consolidation chemotherapy [ 2 ]. The extent of surgical tumor resection is prognostic for survival [ 3 ]; however, recurrence inevitably occurs even when a complete tumor resection on postoperative magnet resonance imaging (MRI) has been achieved. In a subset of patients, changes in the contrast-enhancing (CE) or non-CE tumor portions might even be seen in the interval between the immediate postoperative imaging and imaging obtained prior to radiotherapy for the purpose of target delineation.…”

Predicting Regions of Local Recurrence in Glioblastomas Using Voxel-Based Radiomic Features of Multiparametric Postoperative MRI

“…However, expanding surgical margins is not always feasible because the peritumor can extend to eloquent areas, thus increasing the risk of postoperative neurological deficits. The Response Assessment in Neuro-Oncology (RANO) group recently concluded that less than 5 mL residual non-enhancing tumor volume is prognostically better than complete resection of contrast-enhancing volume alone [ 9 ]. However, the non-enhancing tumor varies in size and location, and a more tailored approach toward the non-enhancing tumor burden could be beneficial.…”