Frontiers

Background: Currently, it is difficult to estimate the possibility of recurrence of nonfunctioning pituitary adenomas (NFPAs). Markers such as Ki-67 or transcription factors rely on postoperative pathology, while few indices can be used for preoperative prediction. Therefore, we aimed to investigate the predictive effectiveness of supra-intrasellar volume and tumor-carotid distance based on measurements derived from preoperative magnetic resonance imaging (MRI) data.

Method: Ninety-eight cases of NFPAs were evaluated, along with their clinical characteristics and MRI features. Four radiologic indices were analyzed, including intrasellar tumor volume, suprasellar tumor volume, maximum horizontal tumor diameter, and intercarotid distance. The ratio of supra-intrasellar volume and ratio of tumor-carotid distance were measured using 3D Slicer software, and the sum of two ratios was defined as the V-D value. The correlation between recurrence and multiple factors was analyzed using univariate and multivariate logistic regression and Kaplan-Meier analysis, and ROC curves were used to estimate the prognostic performance of radiologic measurements in NFPAs.

Result: The supra-intrasellar volume ratio, tumor-carotid distance ratio and V-D value were significantly correlated with the recurrence of NFPAs. The predictive importance of the V-D value reached 84.5%, with a sensitivity of 83.7% and specificity of 67.3%. The cutoff limit of the V-D value was 1.53, and patients with V-D values higher than 1.53 tended to relapse much earlier.

Conclusion: The V-D value has predictive importance for the recurrence of NFPAs preoperatively. Patients with higher V-D values will undergo recurrence earlier and should be given greater consideration in terms of surgery and follow-up time.

Nonfunctioning pituitary adenomas (NFPAs), accounting for 15% - 54% of all types of pituitary adenomas (PAs) (1), are characterized by a lack of hormonal oversecretion except for the high level of prolactin, as well as subclinical or silent hormone dysfunction caused by the “pituitary stalk effect” (2). Over 60% of NFPAs are macroadenomas (diameter over 10 mm), and 57% are invasive (3). Most patients present with headaches, hormone disorders, visual impairment, or cranial nerve palsy. The diagnosis of most NFPAs is usually delayed by a mean time of 1.96 ± 2.9 years due to the absence of endocrine symptoms (4, 5). Complete surgical resection can only be achieved in approximately 40–50% of all patients, although surgery is still the first-line strategy in NFPAs (6). Over 10–20% of cases with gross tumor resection will experience relapse 5–10 years postoperatively. This number rises to 40% and 50% in 5 years and 10 years, respectively, if there is a residual tumor after operation (7).

However, there is a great degree of heterogeneity among cases in terms of tumor recurrence. According to the 2017 WHO classification of brain tumors, most NFPAs are considered gonadotropin adenomas with a low chance of relapse. However, some subtypes of NFPAs, such as silent ACTH adenoma, Pit-1-positive adenomas or plurihormonal adenomas, have a high risk of recurrence but can only be affirmed by postoperative pathological tests. The monoclonal antibody Ki-67 is often used as a tool to aid in recurrence prediction, but its accuracy is still controversial (1). Currently, there are few reliable indices for the prediction of the recurrence of NFPAs (8). The preoperative evaluation still relies on classic methods, including the Hardy-Wilson, and Knosp classifications. Some researchers have reported that these two systems are not effective for precise prediction of tumor recurrence (9–11). The Hardy–Wilson system mainly reflects the longitudinal extension of the tumor, while the Knosp system reflects horizontal invasiveness.

Invasion into the cavernous and/or sphenoid sinus has been proven to be effective in the prediction of recurrence in NFPAs (12) but quantitative analysis is necessary for precise evaluation. Yan et al., have already used the intercarotid distance for the prediction of total resection of PAs, which is closely related to recurrence (13). Therefore, we aim to develop a brief and effective evaluation system using intercarotid distance and supra-intrasellar volume for quantifying the horizontal and longitudinal extension of the tumor. Although many predictive models have already been built, our study aims to provide an evaluation system that is easy to manipulate and use routinely.

A total of 206 patients diagnosed with NFPAs by preoperative pituitary hormones, clinical behavior and postoperative immunohistochemistry were included in this study. After removal of the cases without adequate clinical or radiologic data, 98 cases who had undergone endoscopic trans-sphenoidal surgery in the First Affiliated Hospital, Sun Yat-sen University (Guangzhou, China) between January 2012 and December 2019. were finally selected. According to the tumor size, NFPAs can be classified into small adenomas (tumor largest diameter < 1.5 cm), large adenomas (1.5 1.53) and a small group (V-D