In this study, we demonstrate the clinical and genetic features of iGBMs. They are frequently located in the right hemisphere and in non-eloquent areas and received total or subtotal resection. Although iGBM exhibits unfavorable molecular characteristics, such as IDH-wildtype and MGMT promoter hypomethylation status, it demonstrated favorable clinical outcomes.
The initial signs and symptoms of glioblastoma depend on the location and size of the tumor. Headache (57.3%) was the most common presenting symptom, followed by cognitive changes (38.8%), language deficits (36.2%), and motor deficits (35.9%) . Because there have been no reports of asymptomatic GBM patients, the proportion of asymptomatic patients at the initial presentation in the entire GBM population is still unknown.
This study revealed that iGBM accounted for 1.7% of patients with GBM during the examined period. The incidence may vary among countries and regions depending on the prevalence, resolution, and number of brain imaging performed annually. The brain screening system, familiarly named the “Brain Dock” system, is commercially and commonly available in Japan. This system was first established in 1988 to salvage non-symptomatic intracranial vascular diseases, including ischemic diseases and unruptured cerebral aneurysms , which costs approximately 500 US dollars. This system also contributes to the detection of asymptomatic brain tumors, including meningiomas, pituitary adenomas, and lower-grade gliomas. Based on these social and medical backgrounds, the incidence of iGBM in Japan is higher than the world average.
The laterality and size of the iGBM were unique. The iGBM is exceptionally lean on the right side. Generally, the laterality of GBM is symmetrical as 46–47% of them are right-sided, 42–48% are left-sided, and 6–12% are bilateral or at the central neuroaxis [20, 22]. The tendency of right-sided iGBM is attributed to a functional difference in the left and right brain hemisphere; in 95–99% of right-handed individuals and 70% of left-handed individuals, the left cerebral hemisphere is the dominant hemisphere that controls language . Therefore, tumors in the right hemisphere were less likely to be symptomatic than those on the left side. In addition, the small volume (16.8 cm3) of iGBM, compared to the mean GBM volume of 33.2 cm3 in a previous study , must contribute to the asymptomatic character of iGBM. On the other hand, the tumor location of iGBMs was similar to that of the GBM population; iGBM were found in the temporal, frontal, and parietal lobes, and according to past research, GBM is located at the frontal lobe in 43%, and the temporal lobe in 28% . Furthermore, the gender and age of iGBM are similar to those of general GBM; the incidence of GBM is 1.3–1.6 higher in males than in females [22, 26–28] and the median age of diagnosis is 63–64 years old [22, 26, 27]. The molecular status of iGBM (100% of IDH wild type and 50.0% of TERT promoter mutation) almost agrees with the previous report of 10% IDH1/2 mutations and 74.2% TERT promoter mutation in GBM .
In this study, all iGBMs were removed via either total or subtotal resection. In general, gross or 100% total resection of GBM is only achieved in 20–43% of cases [20, 22]. This favorable result might be due to the surgically optimal characteristics of iGBM, such as small volume and non-dominant hemisphere. Moreover, good perioperative physical and neurological conditions of iGBM patients contribute to tolerance to general anesthesia and complete chemoradiation therapy. As a result, the median PFS and OS of iGBM patients (11.5 and 20.0 months, respectively) were better than previous reports (6.3–7.1 months and 10.1–15.2 months) [9, 10, 13, 15, 27]. It is worth noting that the general patient demographics and molecular features of iGBM were not different from those of general GBM. In summary, iGBM patients have a great advantage in receiving timely therapeutic intervention when they are asymptomatic or before developing severe neurological deterioration.
The main limitation of this study is the small sample size due to the rarity of iGBM; therefore, our results need to be carefully interpreted. The majority of iGBM cases were identified by health screening. Patients who can afford to undergo health screening are considerably wealthy and health-conscious, thus having better physical conditions and broader treatment options. These factors may affect the clinical outcome of iGBMs.