WHO Grade Loses Its Prognostic Value in Molecularly Defined Diffuse Lower-Grade Gliomas

BackgroundWhile molecular insights to diffuse lower-grade glioma (dLGG) have improved the basis for prognostication, most established clinical prognostic factors come from the pre-molecular era. For instance, WHO grade as a predictor for survival in dLGG with isocitrate dehydrogenase (IDH) mutation has recently been questioned. We studied the prognostic role of WHO grade in molecularly defined subgroups and evaluated earlier used prognostic factors in the current molecular setting.Material and MethodsA total of 253 adults with morphological dLGG, consecutively included between 2007 and 2018, were assessed. IDH mutations, codeletion of chromosomal arms 1p/19q, and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions were analyzed.ResultsThere was no survival benefit for patients with WHO grade 2 over grade 3 IDH-mut dLGG after exclusion of tumors with known CDKN2A/B homozygous deletion (n=157) (log-rank p=0.97). This was true also after stratification for oncological postoperative treatment and when astrocytomas and oligodendrogliomas were analyzed separately. In IDH-mut astrocytomas, residual tumor volume after surgery was an independent prognostic factor for survival (HR 1.02; 95% CI 1.01–1.03; p=0.003), but not in oligodendrogliomas (HR 1.02; 95% CI 1.00–1.03; p=0.15). Preoperative tumor size was an independent predictor in both astrocytomas (HR 1.03; 95% CI 1.00–1.05; p=0.02) and oligodendrogliomas (HR 1.05; 95% CI 1.01–1.09; p=0.01). Age was not a significant prognostic factor in multivariable analyses (astrocytomas p=0.64, oligodendrogliomas p=0.08).ConclusionOur findings suggest that WHO grade is not a robust prognostic factor in molecularly well-defined dLGG. Preoperative tumor size remained a prognostic factor in both IDH-mut astrocytomas and oligodendrogliomas in our cohort, whereas residual tumor volume predicted prognosis in IDH-mut astrocytomas only. The age cutoffs for determining high risk in patients with IDH-mut dLGG from the pre-molecular era are not supported by our results.

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Hearing preservation following fractionated stereotactic radiotherapy for vestibular schwannomas: prognostic implications of cochlear dose

Journal of Neurosurgery ◽

10.3171/jns-07/11/0917 ◽

2007 ◽

Vol 107 (5) ◽

pp. 917-926 ◽

Cited By ~ 64

Author(s):

Carys Thomas ◽

Salvatore Di Maio ◽

Roy Ma ◽

Emily Vollans ◽

Christina Chu ◽

...

Keyword(s):

At Risk ◽

Prognostic Factors ◽

Stereotactic Radiotherapy ◽

Tumor Volume ◽

Intensity Modulated Radiotherapy ◽

Hearing Preservation ◽

Fractionated Stereotactic Radiotherapy ◽

Significant Prognostic Factor ◽

Organ At Risk ◽

Radiotherapy Dose

Object The goal in this study was to evaluate hearing preservation rates and to determine prognostic factors for this outcome following fractionated stereotactic radiotherapy (FSRT) of vestibular schwannoma. Methods Thirty-four consecutive patients with serviceable hearing who received FSRT between May 1998 and December 2003 were identified. Clinical and audiometry data were collected prospectively. The prescription dose was 45 Gy in 25 fractions prescribed to the 90% isodose line. The median follow-up duration was 36.5 months (range 12–85 months). The actuarial 2- and 4-year local control rates were 100 and 95.7%, respectively. Permanent trigeminal and facial nerve complications were 0 and 6%, respectively. The actuarial 2- and 3-year serviceable hearing preservation rates were both 63%. The median loss in speech reception threshold was 15 dB (range −10 to 65 dB). The radiotherapy dose to the cochlea was the only significant prognostic factor for hearing deterioration. Radiotherapy dose to the cochlear nucleus, patient age, sex, pre-FSRT hearing grade, tumor volume, and intracanalicular tumor volume failed to show any significance as prognostic factors. Results Five cases were replanned with four different radiotherapy techniques (namely arcs, dynamic arcs, static conformal fields, and intensity-modulated radiotherapy), with the cochlea defined as an organ at risk. In all cases, replanning resulted in statistically significant reduction in radiation to the cochlea (p = 0.001); however, no single replanning technique was found to be superior. Conclusions The radiation dose to the cochlea is strongly predictive for subsequent hearing deterioration. It is essential for the cochlea to be outlined as an organ at risk, and for radiation techniques to be optimized, to improve long-term hearing preservation.

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Risk Factors for Progression in Vestibular Schwannomas After Incomplete Resection: A Single Center Retrospective Study

Frontiers in Neurology ◽

10.3389/fneur.2021.778590 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiuhong Li ◽

Xueyun Deng ◽

Daibo Ke ◽

Jian Cheng ◽

Si Zhang ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Tumor Size ◽

Tumor Volume ◽

Univariate Analysis ◽

Residual Tumor ◽

Vestibular Schwannomas ◽

Incomplete Resection ◽

Cystic Component

Background and Purpose: The risk factors for progression in vestibular schwannomas (VSs) after incomplete resection (IR) remain to be elucidated. The purpose of this study was to investigate the risk factors for progression in remnant VSs after surgery.Methods: From January 2009 to January 2018, 140 consecutive patients who underwent IR of VSs via suboccipital retrosigmoid approach in our institution were retrospectively analyzed. During follow-up, if progression was detected, the patient was classified into Progressive Group (PG); if the residual tumor was stable or shrank, the patient was classified into Stable Group (SG). Univariate analysis and multivariate analysis were used to evaluate the risk factors for progression after IR of VSs.Results: After a mean follow-up of 80.4 months (range, 24–134 months), 35 (25.0%) patients (PG) had a progression, and no progression was detected in 105 (75.0%) patients (SG). The average tumor size was 36.5 ± 8.9 mm in PG and 31.0 ± 9.8 mm in SG, respectively. The residual tumor volume was 304.6 ± 443.3 mm3 in PG and 75.9 ± 60.0 mm3 in SG, respectively. Univariate analysis showed that preoperative tumor size, residual tumor volume, and irregular internal auditory canal (IAC) expansion were significantly different between the two groups, whereas gender, age, cystic component, or Ki-67 labeling index (LI) did not differ significantly between the two groups. Multivariate analysis showed residual tumor volume was the independent risk factor for progression.Conclusions: VSs that underwent IR with larger preoperative size, greater residual tumor volume, or irregular IAC expansion may have a higher progression rate. Strict follow-up with shorter interval in these patients to detect early progression is necessary.

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Factors triggering an additional resection and determining residual tumor volume on intraoperative MRI: analysis from a prospective single-center registry of supratentorial gliomas

Neurosurgical FOCUS ◽

10.3171/2015.11.focus15542 ◽

2016 ◽

Vol 40 (3) ◽

pp. E4 ◽

Cited By ~ 20

Author(s):

Moritz Scherer ◽

Christine Jungk ◽

Alexander Younsi ◽

Philipp Kickingereder ◽

Simon Müller ◽

...

Keyword(s):

Prediction Model ◽

Tumor Volume ◽

Case Series ◽

Residual Tumor ◽

Intraoperative Mri ◽

Related Factors ◽

Glioma Surgery ◽

Who Grade ◽

Supratentorial Gliomas ◽

Additional Resection

OBJECTIVE In this analysis, the authors sought to identify variables triggering an additional resection (AR) and determining residual intraoperative tumor volume in 1.5-T intraoperative MRI (iMRI)-guided glioma resections. METHODS A consecutive case series of 224 supratentorial glioma resections (WHO Grades I–IV) from a prospective iMRI registry (inclusion dates January 2011–April 2013) was examined with univariate and multiple regression models including volumetric data, tumor-related, and surgeon-related factors. The surgeon's expectation of an AR, in response to a questionnaire completed prior to iMRI, was evaluated using contingency analysis. A machine-learning prediction model was applied to consider if anticipation of intraoperative findings permits preoperative identification of ideal iMRI cases. RESULTS An AR was performed in 70% of cases after iMRI, but did not translate into an accumulated risk for neurological morbidity after surgery (p = 0.77 for deficits in cases with AR vs no AR). New severe persistent deficits occurred in 6.7% of patients. Initial tumor volume determined frequency of ARs and was independently correlated with larger tumor remnants delineated on iMRI (p < 0.0001). Larger iMRI volume was further associated with eloquent location (p = 0.010) and recurrent tumors (p < 0.0001), and with WHO grade (p = 0.0113). Greater surgical experience had no significant influence on the course of surgery. The surgeon's capability of ruling out an AR prior to iMRI turned out to incorporate guesswork (negative predictive value 43.6%). In a prediction model, AR could only be anticipated with 65% accuracy after integration of confounding variables. CONCLUSIONS Routine use of iMRI in glioma surgery is a safe and reliable method for resection guidance and is characterized by frequent ARs after scanning. Tumor-related factors were identified that influenced the course of surgery and intraoperative decision-making, and iMRI had a common value for surgeons of all experience levels. Commonly, the subjective intraoperative impression of the extent of resection had to be revised after iMRI review, which underscores the manifold potential of iMRI guidance. In combination with the failure to identify ideal iMRI cases preoperatively, this study supports a generous, tumor-oriented rather than surgeon-oriented indication for iMRI in glioma surgery.

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Transcriptomic Analysis of Glioma Based on IDH Status Identifies ACAA2 as a Prognostic Factor in Lower Grade Glioma

BioMed Research International ◽

10.1155/2020/1086792 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Chenxing Wu ◽

Hongwang Song ◽

Xiaojun Fu ◽

Shouwei Li ◽

Tao Jiang

Keyword(s):

Prognostic Factor ◽

Network Analysis ◽

Targeted Therapies ◽

Correlation Network ◽

Lower Grade ◽

Gene Expressions ◽

Who Grade ◽

Lower Grade Glioma ◽

Idh Mutations ◽

Weighted Correlation

Background. Glioma is the most common and lethal tumor in the central nervous system (CNS). More than 70% of WHO grade II/III gliomas were found to harbor isocitrate dehydrogenase (IDH) mutations which generated targetable metabolic vulnerabilities. Focusing on the metabolic vulnerabilities, some targeted therapies, such as NAMPT, have shown significant effects in preclinical and clinical trials. Methods. We explored the TCGA as well as CGGA database and analyzed the RNA-seq data of lower grade gliomas (LGG) with the method of weighted correlation network analysis (WGCNA). Differential expressed genes were screened, and coexpression relationships were grouped together by performing average linkage hierarchical clustering on the topological overlap. Clinical data were used to conduct Kaplan–Meier analysis. Results. In this study, we identified ACAA2 as a prognostic factor in IDH mutation lower grade glioma with the method of weighted correlation network analysis (WGCNA). The difference of ACAA2 gene expressions between the IDH wild-type (IDH-WT) group and the IDH mutant (IDH-MUT) group suggested that there may be different potential targeted therapies based on the fatty acid metabolic vulnerabilities, which promoted the personalized treatment for LGG patients.

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Postoperative Prolonged Mechanical Ventilation in Patients With Newly Diagnosed Glioblastoma—An Unrecognized Prognostic Factor

Frontiers in Oncology ◽

10.3389/fonc.2020.607557 ◽

2020 ◽

Vol 10 ◽

Author(s):

Patrick Schuss ◽

Felix Lehmann ◽

Niklas Schäfer ◽

Christian Bode ◽

Elisa Scharnböck ◽

...

Keyword(s):

Mechanical Ventilation ◽

Prognostic Factors ◽

Prognostic Factor ◽

Functional Outcome ◽

Prolonged Mechanical Ventilation ◽

Methylation Status ◽

Significant Prognostic Factor ◽

Karnofsky Performance Score ◽

Newly Diagnosed ◽

Newly Diagnosed Glioblastoma

ObjectiveAlthough the treatment of glioblastoma patients is well established in neuro-oncological surgery, precious scarce data is available on patients with glioblastoma requiring postoperative prolonged mechanical ventilation (PMV). Therefore, the aim of the present study was to determine the influence of PMV on overall survival (OS) in patients with glioblastoma.MethodsPatients with newly diagnosed glioblastoma who had undergone surgical therapy and complete subsequent neuro-oncological treatment at the authors’ neuro-oncological center from January 2013 to December 2018 were selected and included in the further analysis. PMV was defined as mechanical ventilation for more than 24 h after surgery. Survival analyses were performed, including established prognostic factors such as age, Karnofsky performance score, MGMT-promoter methylation status and extent of resection.ResultsA total of 240 patients with newly diagnosed glioblastoma and subsequent surgical treatment were identified. 13 patients (5%) suffered from PMV during the treatment course of glioblastoma. All but one patient were successfully weaned from mechanical ventilation. Patients suffering from PMV achieved significantly less often favorable functional outcome after 3, 6, 9, and 12 months compared to patients without PMV. Multivariate analysis revealed PMV to constitute a significant prognostic factor for OS, independent of other prognostic factors (p<0.0001, OR 6.7, 95% CI 3.2–13.8).ConclusionsThe present study identifies PMV as significantly associated with impaired functional outcome and poor OS in patients suffering from newly diagnosed glioblastoma. These findings encourage further efforts to investigate/assess this prognostic factor in future studies.

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Prognostic factors for response and survival of second-line chemotherapy in patients with relapsed small cell lung cancer (SCLC)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18023 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18023-18023

Author(s):

Y. Kim ◽

K. Goto ◽

K. Yoh ◽

S. Niho ◽

H. Ohmatsu ◽

...

Keyword(s):

Prognostic Factors ◽

Prognostic Factor ◽

Response Duration ◽

Significant Prognostic Factor ◽

Second Line ◽

Clinical Factors ◽

Second Line Chemotherapy ◽

Extent Of Disease ◽

Line Chemotherapy ◽

Sensitive Relapse

18023 Background: Despite high response rates to initial chemotherapy, the majority of patients with SCLC experience tumor progression. Previous studies showed that both the response to initial chemotherapy and the response duration are important for predicting the efficacy of second-line chemotherapy. Therefore, relapsed SCLC is commonly classified into two groups: sensitive relapse (respond to initial chemotherapy and relapse more than 3 months after the completion of initial chemotherapy) and refractory relapse (not respond to initial chemotherapy or respond but relapse within 3 months). However, prognostic factors of the second-line chemotherapy have not been fully understood. Methods: From July 1992 to December 2003, four hundred and seventy-four patients with SCLC received chemotherapy as initial treatment, subsequently 229 patients received second-line chemotherapy (144 sensitive relapse and 85 refractory relapse) in our hospital. We analyzed the association of patients’ clinical factors with response and survival of second-line chemotherapy in sensitive relapsed patients and refractory relapsed patients, separately. For sensitive relapsed patients, analyzed clinical factors were as follows: age (<70/=70), gender (M/F), response to initial chemotherapy (CR/PR), PS at relapse (<2/=2) and the extent of disease at relapse (LD/ED). For refractory relapsed patients, analyzed clinical factors were as follows: age (<70/=70), gender (M/F), response to initial chemotherapy (responder/non-responder), PS at relapse (<2/=2) and the extent of disease at relapse (LD/ED). Results: Response to second-line chemotherapy was significantly correlated with PS in sensitive relapsed patients, however, no significant factor was detected in refractory relapsed patients. For survival, PS was the only significant prognostic factor in both sensitive and refractory relapsed patients. The median survival time was 328 days (PS<2) and 128 days (PS=2) in sensitive relapsed patients (p<0.0001), while 195 days (PS<2) and 113 days (PS=2) in refractory relapsed patients (p=0.0001), respectively. Conclusions: PS was the only significant prognostic factor for survival both in sensitive and refractory relapsed SCLC. No significant financial relationships to disclose.

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A pooled analysis of 1,546 patients with AIDS-related lymphoma (ARL): An assessment of prognostic factors by treatment era.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8524 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8524-8524

Author(s):

Stefan K. Barta ◽

Michael Samuel ◽

Xiaonan Xue ◽

Jeanette Y. Lee ◽

Nicolas Mounier ◽

...

Keyword(s):

Prognostic Factors ◽

Prognostic Factor ◽

Prognostic Significance ◽

Pooled Analysis ◽

Cd4 Count ◽

Significant Prognostic Factor ◽

Poor Prognostic Factor ◽

Risk Of Death ◽

Time Period ◽

Increased Risk

8524 Background: Management of ARL evolved in the last 2 decades. We previously reported prognostic factors in a pooled analysis of 1,546 patients with ARL, and here present analysis of these factors over time to determine if their prognostic significance has changed. Methods: Following a systematic review, we assembled individual patient data from 19 prospective phase 2/3 clinical trials (published 1993-2010) for ARL (n=1,546). Factors analyzed include age, sex, histology, CD4 count, prior history of (h/o) AIDS, & age-adjusted (aa) IPI. The endpoint was overall survival (OS) expressed as the hazard ratio (HR) for death. We used separate Cox proportional hazard models adjusted for the other covariates to determine the significance of each variable in the following time periods: pre-cART [combination antiretroviral therapy] (<1996; n=388), early cART (‘96-‘00; n=694), modern cART (‘01-‘04; n=282) & current era (‘05-‘10; n=182). We also combined all enrollments in one Cox model to test for difference in association with OS over enrollment periods. Results: Rituximab use was limited in the early cART (20%) compared with the modern cART (83%) and current (93%) eras. Histology & sex were not significantly associated with OS in any time period. Increasing age was associated with worse OS in the pre-cART (HR 1.02; p<0.01) and current (HR 1.05, p=0.04) eras. A prior h/o AIDS increased risk of death during early cART (HR 1.31, p=0.047) but was not significant after 2000. Meanwhile, baseline CD4 count <50 was a poor prognostic factor during early (HR 1.78, p<0.01) and modern cART (HR 2.76, p=0.001) eras, but not in the current era. The aaIPI predicted worse OS in each time period (pre-cART: HR 1.54, p<0.0001; early cART: HR 1.49, p<0.0001; modern cART: HR 1.52, p<0.01; current era: HR 2.34, p<0.0001). No significant interaction between each prognostic factor with enrollment was found. Conclusions: In this pooled analysis of 1,546 patients with ARL, aaIPI was the only consistently significant prognostic factor and its effect was magnified in the current era. HIV-related factors gained prognostic relevance in the early and modern cART era but may not be as relevant with current treatment strategies.

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Alteration of recurrence patterns and prognostic factors by adjuvant S-1 monotherapy in patients with stage II/III gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.90 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 90-90

Author(s):

Mitsuro Kanda ◽

Daisuke Kobayashi ◽

Chie Tanaka ◽

Naoki Iwata ◽

Suguru Yamada ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factors ◽

Tumor Size ◽

Propensity Score Analysis ◽

Treatment Options ◽

Stage Ii ◽

Significant Prognostic Factor ◽

Initial Recurrence ◽

Macroscopic Tumor ◽

Recurrence Patterns

90 Background: Survival benefit of adjuvant S-1 monotherapy among East Asian patients with stage II/III gastric cancer (GC) has been demonstrated by the ACTS-GC trial. Little is known about the changes in prognostic factors and recurrence patterns after it has become widespread as a standard of care. Methods: We enrolled 171 patients with stage II/III GC, 92 patients who underwent gastrectomy alone, and 79 patients treated with S-1 adjuvant. To balance more strictly the essential variables including stage of progression, we conducted propensity score analysis and 70 pairs of patients were generated from each group. Prognostic factors were compared between the groups and initial recurrence patterns were investigated to explore reasons for the change. Results: In concordance with the previous phase 3 trial, overall and recurrence-free survival were better for the S-1 adjuvant group. In the surgery alone group, carcinoembryonic antigen > 5 ng/mL, total gastrectomy, vessel invasion, pT4, and stage 3 were identified as significant prognostic factors. In striking contrast, macroscopic tumor size > 50 mm was the only significant prognostic factor for the S-1 adjuvant group. The lower overall recurrence rate of the S-1 adjuvant group was attributable mainly to a significant decrease of peritoneal recurrence. Conclusions: Prognostic factors changed substantially after implementation of S-1 adjuvant treatment. Macroscopic tumor size should be considered for patient stratification and selection of treatment options for patients with stage II/III GC.

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Maximum tumor dimension and tumor volume as prognostic factors in patients with newly diagnosed localized Ewing sarcoma (ES)- a report from the Children’s Oncology Group (COG).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.11529 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 11529-11529

Author(s):

Leo Mascarenhas ◽

Allen Buxton ◽

Steven G. DuBois ◽

Dian Wang ◽

Nadia N. Laack ◽

...

Keyword(s):

Clinical Trial ◽

Prognostic Factors ◽

Tumor Size ◽

Tumor Volume ◽

Cox Model ◽

Rank Test ◽

Newly Diagnosed ◽

Phase 3 ◽

Increased Risk ◽

Significant Difference

11529 Background: Maximum tumor dimension > 8 cm. and large tumor volume have been reported to be adverse prognostic factors in patients with ES but have not been prospectively evaluated in the context of a phase 3 clinical trial with interval compressed chemotherapy. Methods: COG AEWS1031 (NCT01231906) was a randomized phase 3 clinical trial comparing interval compressed chemotherapy regimens in patients with newly diagnosed localized ES of bone and soft tissue. A correlative objective of AEWS1031 was to evaluate tumor size and volume as prognostic factors. Institution-reported dimensions of the primary tumor from baseline imaging were prospectively collected. For inclusion in this analysis, patients had to have at least 1 tumor dimension reported for tumor size analyses and dimensions in 3 axes for tumor volume analyses. Maximum dimension was dichotomized as less than vs. > / = 8cm. Tumor volume was dichotomized as less than vs. > / = 200 mL. Event-free (EFS) and overall survival (OS) from enrollment were calculated using Kaplan-Meier methods and compared between groups using a two-sided log-rank test. Hazard ratios (HR) and confidence intervals (CI) were calculated using the Cox model. Results: The 5-year EFS and OS of the 629 eligible patients was 78% (95% CI: 75-81%) and 87% (95% CI: 84-90%) respectively and there was no significant difference in both EFS and OS between the randomized interval compressed chemotherapy arms of AEWS1031. 590 of 629 (94%) patients were evaluable for maximum tumor dimension and 307 (52%) had tumors > / = 8 cm. Patients with tumors > / = 8 cm were at significantly increased risk for EFS events (p = 0.016) with estimated 5-year EFS of 73.7% (95% CI: 68.1 vs.78.4%) vs. 82.9% (95% CI 77.7-87.1%) for patients with tumors < 8 cm [HR: 1.53 (1.08-2.17)]. For tumor volume, 586 of 629 patients (93%) were evaluable and 180 (31%) had tumors > / = 200 mL. Patients with tumor volume > / = 200 mL were at significantly increased risk for EFS events (p = 0.003) with estimated 5-year EFS of 70% (95% CI: 62.3-76.4%) vs. 81.6% (95% CI: 77.2-85.2%) for patients with tumors < 200 mL [HR: 1.69 (1.2-2.39)]. Conclusions: Maximum tumor dimension and tumor volume as defined are both prognostic in patients with newly diagnosed localized ES treated with interval compressed chemotherapy. Clinical trial information: NCT01231906 .

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Contemporary assessment of extent of resection in molecularly defined categories of diffuse low-grade glioma: a volumetric analysis

Journal of Neurosurgery ◽

10.3171/2019.6.jns19972 ◽

2020 ◽

Vol 133 (5) ◽

pp. 1291-1301 ◽

Cited By ~ 5

Author(s):

Vasileios K. Kavouridis ◽

Alessandro Boaro ◽

Jeffrey Dorr ◽

Elise Y. Cho ◽

J. Bryan Iorgulescu ◽

...

Keyword(s):

Tumor Volume ◽

Cox Regression ◽

Molecular Subtypes ◽

Progression Free Survival ◽

Residual Tumor ◽

Extent Of Resection ◽

Low Grade Glioma ◽

Low Grade ◽

Who Grade ◽

Free Survival

OBJECTIVEWhile the effect of increased extent of resection (EOR) on survival in diffuse infiltrating low-grade glioma (LGG) patients is well established, there is still uncertainty about the influence of the new WHO molecular subtypes. The authors designed a retrospective analysis to assess the interplay between EOR and molecular classes.METHODSThe authors retrospectively reviewed the records of 326 patients treated surgically for hemispheric WHO grade II LGG at Brigham and Women’s Hospital and Massachusetts General Hospital (2000–2017). EOR was calculated volumetrically and Cox proportional hazards models were built to assess for predictive factors of overall survival (OS), progression-free survival (PFS), and malignant progression–free survival (MPFS).RESULTSThere were 43 deaths (13.2%; median follow-up 5.4 years) among 326 LGG patients. Median preoperative tumor volume was 31.2 cm3 (IQR 12.9–66.0), and median postoperative residual tumor volume was 5.8 cm3 (IQR 1.1–20.5). On multivariable Cox regression, increasing postoperative volume was associated with worse OS (HR 1.02 per cm3; 95% CI 1.00–1.03; p = 0.016), PFS (HR 1.01 per cm3; 95% CI 1.00–1.02; p = 0.001), and MPFS (HR 1.01 per cm3; 95% CI 1.00–1.02; p = 0.035). This result was more pronounced in the worse prognosis subtypes of IDH-mutant and IDH-wildtype astrocytoma, for which differences in survival manifested in cases with residual tumor volume of only 1 cm3. In oligodendroglioma patients, postoperative residuals impacted survival when exceeding 8 cm3. Other significant predictors of OS were age at diagnosis, IDH-mutant and IDH-wildtype astrocytoma classes, adjuvant radiotherapy, and increasing preoperative volume.CONCLUSIONSThe results corroborate the role of EOR in survival and malignant transformation across all molecular subtypes of diffuse LGG. IDH-mutant and IDH-wildtype astrocytomas are affected even by minimal postoperative residuals and patients could potentially benefit from a more aggressive surgical approach.

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