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. 2021 Dec 13:11:748691.
doi: 10.3389/fonc.2021.748691. eCollection 2021.

A Continuous Correlation Between Residual Tumor Volume and Survival Recommends Maximal Safe Resection in Glioblastoma Patients: A Nomogram for Clinical Decision Making and Reference for Non-Randomized Trials

Marco Skardelly  1   2 , Marlene Kaltenstadler  1 , Felix Behling  1 , Irina Mäurer  3   4 , Jens Schittenhelm  5 , Benjamin Bender  6 , Frank Paulsen  2   7 , Jürgen Hedderich  8 , Mirjam Renovanz  1   2   3   4   9 , Jens Gempt  10 , Melanie Barz  10 , Bernhard Meyer  10 , Ghazaleh Tabatabai  1   2   3   4 , Marcos Soares Tatagiba  1   2
Affiliations

A Continuous Correlation Between Residual Tumor Volume and Survival Recommends Maximal Safe Resection in Glioblastoma Patients: A Nomogram for Clinical Decision Making and Reference for Non-Randomized Trials

Marco Skardelly et al. Front Oncol. .

Abstract

Objective: The exact role of the extent of resection or residual tumor volume on overall survival in glioblastoma patients is still controversial. Our aim was to create a statistical model showing the association between resection extent/residual tumor volume and overall survival and to provide a nomogram that can assess the survival benefit of individual patients and serve as a reference for non-randomized studies.

Methods: In this retrospective multicenter cohort study, we used the non-parametric Cox regression and the parametric log-logistic accelerated failure time model in patients with glioblastoma. On 303 patients (training set), we developed a model to evaluate the effect of the extent of resection/residual tumor volume on overall survival and created a score to estimate individual overall survival. The stability of the model was validated by 20-fold cross-validation and predictive accuracy by an external cohort of 253 patients (validation set).

Results: We found a continuous relationship between extent of resection or residual tumor volume and overall survival. Our final accelerated failure time model (pseudo R2 = 0.423; C-index = 0.749) included residual tumor volume, age, O6-methylguanine-DNA-methyltransferase methylation, therapy modality, resectability, and ventricular wall infiltration as independent predictors of overall survival. Based on these factors, we developed a nomogram for assessing the survival of individual patients that showed a median absolute predictive error of 2.78 (mean: 1.83) months, an improvement of about 40% compared with the most promising established models.

Conclusions: A continuous relationship between residual tumor volume and overall survival supports the concept of maximum safe resection. Due to the low absolute predictive error and the consideration of uneven distributions of covariates, this model is suitable for clinical decision making and helps to evaluate the results of non-randomized studies.

Keywords: accelerated failure time; extent of resection; glioblastoma; nomogram; prognostic survival model; reference; residual tumor volume.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overall survival curves. Overall survival shown in Kaplan–Meier estimates and derived from Cox regression and log-logistic regression.
Figure 2
Figure 2
Relationship between residual tumor volume (RTV) and overall survival (OS). Relationship between predicted OS and RTV or extent of resection (EOR) as single predictors in a log-logistic regression model. Both curves show a continuous, nearly linear relationship and run in parallel with a better prognosis for relative RTV (EOR), suggesting that preoperative tumor size also may have an effect on OS.
Figure 3
Figure 3
Nomogram for predicting overall survival (OS). Final nomogram predicting individual median survival times and 12, 24, and 60 months of survival probability based on six predictors of OS, which add up in a summary score from 0 (worst) to 34 (best) total points; for examples, see table, Supplementary File 4 , with four clinical cases of nomogram-predicted survival versus actual survival.
Figure 4
Figure 4
Prognostic diagrams for overall survival (OS). Prognostic diagrams for the median OS (full line, right y-axis) and 12, 24, and 60 months (dashed lines, left y-axis) survival probability based on the total prognostic scores of the nomogram.
See this image and copyright information in PMC

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