In this study, we compared SRS outcomes for VSs between younger and older patients. No significant between-cohort differences were found in the tumor control rate based on multivariate analysis or through comparisons using PS matching. There were no significant between-cohort differences in the incidence of facial and trigeminal nerve deficits after SRS. The crude hearing preservation rate was 44% in the younger cohort, which was similar to that in the older cohort.
Regarding surgical resection for VS, Sughrue et al. evaluated outcomes in 208 patients aged < 40 years (median follow-up, 10.2 years) . Surgical resection led to durable long-term freedom from tumor recurrence or progression in 89% of patients at 15 years follow-up. However, studies concerning SRS in younger patients with VS are scarce. Most studies that included patients of all ages have not confirmed whether age could influence tumor control; although age groups varied, few studies have focused on outcomes in young adults. In 2009, one study reported that the tumor control rate in patients aged ≤ 40 years was 96% at 5 years and that the incidence of cranial nerve deficits was extremely rare at the median follow-up period of 5.3 years . Through comparisons with an older cohort using PS matching, our study results indicated that SRS was equally effective for younger patients. Moreover, our longer follow-up period provided additional supportive evidence of long-term durability.
Careful consideration is required when managing patients following SRS. It can be challenging to differentiate between true tumor progression and pseudo-progression, in particular, for younger patients, where the threshold of salvage surgery may be lowered, as additional resections are generally tolerable in this age group. Recent studies, in contrast to conventional wisdom, have shown that transient expansion may occur later than 2 years post-SRS and the growth rate may occasionally exceed 50% in volume increase [23–25]. Thus, tumors not causing disturbing symptoms or brainstem compression may be amenable to observation despite a certain rate of progression. Close discussion with skull-base surgeons is likely to enhance the decision-making process.
Previous studies have reported possible advantages in younger patients after SRS, for example, a reduced risk of hydrocephalus and balance disturbance . This could not be determined in our study because of the small number of patients who underwent a shunting procedure in our cohort. Some controversy exists in terms of age effects on hearing preservation. Consistent with previous studies [27, 28], the present study suggests that younger age may be non-advantageous for hearing preservation. This finding may be partly due to the present study eligibility criteria, which included patients with a shorter observation period. It may also imply that maintaining long-term hearing function remains challenging due to various risk factors intrinsic to VS , namely, the influence of irradiation and ischemic, mechanical, or chemical damage to the cochlear nerve due to VS itself [29, 30]. However, advantages of younger age concerning hearing preservation have also been reported . The Pittsburgh Hearing Prediction Score has been proposed as a method to predict long-term hearing outcomes prior to primary SRS . In this scoring system, younger age, smaller tumor, and better hearing function prior to SRS have been shown to predict hearing preservation. Therefore, SRS for the selected patients with favorable hearing function remains promising as a first option; this recommendation should be verified in future clinical trials.
Delayed adverse radiation events are rare but problematic. Regarding aneurysm formation in the irradiated field, only 11 cases have been reported to date, one of which was a case we previously reported [25, 33–38]. All the aneurysms were reported to be pseudoaneurysms and prone to rupture. The pathogenesis is unknown; however, given that most of the reported patients were aged > 40 years at SRS, aging-related factors such as atherosclerosis may play a role alongside irradiation. Another significant concern is malignant transformation, which has been reported in more than 10 studies to date. However, only nine true radiation-induced malignancies have fulfilled Cahan’s criteria , namely, cases showing histopathological evidence of transformation [20, 40–46]. Neurofibromatosis type 2-related VS was the only possible risk factor and, based on systematic review findings, the incidence of malignant transformation is approximately 0.016% in sporadic VS cases following SRS with a latency period of up to 10 years . Therefore, SRS should not be excluded as a therapeutic option for younger patients, provided long-term surveillance with MRI is feasible after SRS.
This study had several limitations. First, this study included a small sample of young adults. We included patients who underwent primary SRS and those who underwent salvage SRS after resection, possibly for relatively aggressive tumors. Although the variable of salvage SRS was adjusted after PS matching, a future study with only young patients without any intervention would be helpful. Second, hearing evaluation was not comprehensive due to the lack of speech discrimination score data. This could have influenced the hearing outcome, along with a relatively higher marginal dose in the younger cohort. Finally, even though we focused on younger patients, the younger cohort mainly comprised patients in their 30s; thus, this study did not sufficiently address outcomes in even younger patients. In theory, VSs in pediatric or very young patients could have different biological characteristics or might not be distinguishable from neurofibromatosis type 2; thus, more careful consideration is required . Despite these limitations, this study contributes to the body of knowledge and is likely to be useful for decision-making regarding SRS for young adults with VS.