Prognostic evaluation of re-resection for recurrent glioblastoma using the novel RANO classification for extent of resection: A report of the RANO resect group

Abstract

Background The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome. Methods The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were constructed to minimize confounding effects when comparing the different RANO classes. Results We studied 681 patients with first recurrence of Isocitrate Dehydrogenase (IDH) wild-type glioblastomas, including 310 patients who underwent re-resection. Re-resection was associated with prolonged survival even when stratifying for molecular and clinical confounders on multivariate analysis; ≤1 cm3 residual CE tumor was associated with longer survival than non-surgical management. Accordingly, “maximal resection” (class 2) had superior survival compared to “submaximal resection” (class 3). Administration of (radio-)chemotherapy in the absence of postoperative deficits augmented the survival associations of smaller residual CE tumors. Conversely, “supramaximal resection” of non-CE tumor (class 1) was not associated with prolonged survival but was frequently accompanied by postoperative deficits. The prognostic role of residual CE tumor was confirmed in propensity score analyses. Conclusions The RANO resect classification serves to stratify patients with re-resection of glioblastoma. Complete resection according to RANO resect classes 1 and 2 is prognostic.

How to evaluate extent of resection in diffuse gliomas: from standards to new methods

“…Interestingly, the notion on the significance of residual tumor volume seems also to be retained for non-CE tumor as Molinaro et al [4] outlined that smaller residual non-CE tumors are associated with even more favorable outcomes among patients without any postoperative CE tumor. Such an assumption was further supported by more recent findings of the RANO resect group [5 ▪▪ ], and a classification system for extent of resection based upon the residual tumor volumes has been proposed for glioblastoma patients as follows [5 ▪▪ ,6 ▪ ]:…”

“…Recently, the RANO resect group reported on a molecularly well defined cohort of 310 patients with glioblastoma, IDH-wildtype who underwent re-resection. Here, complete resection corresponding to the above outlined RANO resect classes 1 and 2 were associated with favorable outcome after stratifying for clinical and molecular confounders [6 ▪ ]. Studies on large cohorts evaluating the value of re-resection in low-grade diffuse gliomas are currently still missing.…”

“…Across all diffuse gliomas, microsurgical tumor resection whenever safely possible represents the current standard of care enabling further adjuvant (radio-)chemotherapy by establishing a tissue-based diagnosis [3]. Besides providing tissue for neuropathological assessment, extent of resection (EOR) has been shown to be associated with favorable outcome in both IDH-wildtype glioblastoma and IDH-mutant glioma [4,5 ▪▪ ,6 ▪ ,7 ▪▪ ]. Here, evidence has emerged that the association between more extensive EOR and favorable survival is due to oncological effects of the surgery rather and not only explained by an inherently worse prognosis of subtotally resected tumors due to proximity of such tumors to critical brain regions.…”

Surgical Management and Advances in the Treatment of Glioma

“…28 More definitively, the RANO resect study group evaluated 681 IDH-wt HGG patients, controlled for MGMT mutation status, and used imaging-based volumetric analyses with detailed classification of EOR according to the RANO resect criteria. 29 Re-resection had a significant impact on PRS (11 vs. 7 months, p ¼ 0.001) in the unadjusted cohort which persisted even when controlling for confounders in a multivariate model (p ¼ 0.001). Furthermore, they corroborated the findings of the DIRECTOR trial analysis on the impact of EOR of the CE portions of the tumor, demonstrating a positive survival impact only with class 1 and 2 EOR but not class 3.…”

Artificial intelligence in neuroimaging of brain tumors: reality or still promise?

“…The current standard of care for surgical treatment of aggressive brain tumors such as glioblastoma is gross total resection, the goal of which is complete resection of enhancing tumor seen on imaging. However, it is well known that nonenhancing abnormality in the peritumoral region often contains infiltrative tumor where disease can recur and has additional prognostic value independent of the enhancing disease [30]. Furthermore, resection of nonenhancing tumor improves overall survival [31].…”