Abstract
BackgroundThe Ki-67 index is an indicator of proliferation and aggressive behavior in pituitary adenomas (PAs). This study aims to develop and validate a predictive nomogram for forecasting Ki-67 index levels preoperatively in PAs.MethodsA total of 439 patients with PAs underwent PA resection at the Department of Neurosurgery in Jinling Hospital between January 2018 and October 2020; they were enrolled in this retrospective study and were classified randomly into a training cohort (n = 300) and a validation cohort (n = 139). A range of clinical, radiological, and laboratory characteristics were collected. The Ki-67 index was classified into the low Ki-67 index (<3%) and the high Ki-67 index (≥3%). Least absolute shrinkage and selection operator algorithm and uni- and multivariate logistic regression analyses were applied to identify independent risk factors associated with Ki-67. A nomogram was constructed to visualize these risk factors. The receiver operation characteristic curve and calibration curve were computed to evaluate the predictive performance of the nomogram model.ResultsAge, primary-recurrence subtype, maximum dimension, and prolactin were included in the nomogram model. The areas under the curve (AUCs) of the nomogram model were 0.694 in the training cohort and 0.658 in the validation cohort. A well-fitted calibration curve was also generated for the nomogram model. A subgroup analysis revealed stable predictive performance for the nomogram model. A correlation analysis revealed that age (R = −0.23; p < 0.01), maximum dimension (R = 0.17; p < 0.01), and prolactin (R = 0.16; p < 0.01) were all significantly correlated with the Ki-67 index level.ConclusionsAge, primary-recurrence subtype, maximum dimension, and prolactin are independent predictors for the Ki-67 index level. The current study provides a novel and feasible nomogram, which can further assist neurosurgeons to develop better, more individualized treatment strategies for patients with PAs by predicting the Ki-67 index level preoperatively.
Highlights
Pituitary adenomas (PAs), which account for approximately 15% of primary intracranial neoplasms, are the most common tumors in the sellar region [1]
The clinical information of patients with PAs in the high Ki-67 cohort and in the low Ki-67 cohort, which was summarized in Table 1 and Table S3, revealed remarkable differences in the following variables: age, clinical subtype, Hardy grade for suprasellar extension, history of pituitary surgery, multiple lesions, maximum dimension, luteinizing hormone (LH), folliclestimulating hormone (FSH), free triiodothyronine (FT3), Creactive protein, red blood cell (RBC) count, creatinine, potassium, procalcitonin (PCT), lymphocyte percentage, urea, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), fibrin/fibrinogen degradation products, thrombocytocrit, and platelet counts
In the subgroup, according to the maximum dimension subtype and clinical subtype, we discovered a positive correlation and a negative correlation between the Ki-67 index and maximum dimension in the macroadenoma (R = 0.17; p < 0.01) and microadenoma (R = −0.62; p = 0.02) subgroups, respectively (Figures S2H, I; Table 4), which was consistent with the results from the research by Turner et al A significant positive correlation between Ki-67 index and maximum dimension was revealed in growth hormone (GH) (R = 0.30; p = 0.01) and PRL (R = 0.32; p = 0.05) secreting PA subgroups (Figures S2L, M and Table 4)
Summary
Pituitary adenomas (PAs), which account for approximately 15% of primary intracranial neoplasms, are the most common tumors in the sellar region [1]. The French five-tiered classification is another approach for classifying PAs with validated prognostic value, and Ki-67 is used as one of the proliferative markers [2]. How to integrate machine learning model into the routine practices have not been assessed so far [9]. Conficoni et al suggested that quantitative measures of apparent diffusion coefficient (ADC) values could predict the Ki67 value [10]. This value was not routinely assessed in clinical practice. The Ki-67 index is an indicator of proliferation and aggressive behavior in pituitary adenomas (PAs). This study aims to develop and validate a predictive nomogram for forecasting Ki-67 index levels preoperatively in PAs
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