Efficacy of intensity-modulated radiation therapy for optic nerve sheath meningioma

Optic nerve sheath meningioma (ONSM) is a relatively rare tumor, accounting for 1–2% of all meningiomas [1, 2]. Developing from the arachnoid cap cells of the optic nerve sheath, these benign and slowly progressive tumors cause optic nerve insult through compression and vascular compromise, resulting in severe visual impairment that may lead to blindness [3]. Tumor may grow intracranially through the optic canal to involve the optic chiasm and the contralateral optic nerve. Hence, it is of paramount importance to stop or reverse the growth of the tumor. In the treatment of ONSM, preservation of vision following tumor resection is known to be difficult, because surgery precipitates complications that damage the pial vascular plexus nourishing the optic nerve in many cases, leaving 95% of patients with severe postoperative visual impairment [1]. Surgery is currently indicated when esthetic issues arise following loss of vision or when intracranial tumor extension impacts prognosis for survival. In recent years, stereotactic radiotherapy (SRT), in the broad sense of the term, has been reported as an effective alternative to surgery [4, 5].

Intensity-modulated radiation therapy (IMRT) uses a device such as a multileaf collimator to adjust spatial and temporal radiation intensity and irradiate a precise focal target from multiple directions, thereby achieving optimal dose distribution on a three-dimensional plane. An advanced version of conventional stereotactic radiation therapy that is more effective and non-invasive, this new system reduces exposure to surrounding tissue by enabling modulation of dose intensity within the radiation field. Studies have already shown the advantages of IMRT for treating various intracranial tumors and skull base meningiomas [6‐9]. The optic nerve is highly sensitive to radiation and therefore requires precision radiotherapy to avoid severe radiation-induced optic neuropathy. Detailed research into IMRT outcomes in the treatment of ONSM is lacking. As such, the present study examined the efficacy and complications associated with IMRT for ONSM by applying the technique to a large number of cases and comparing visual function before and after treatment.

In the context of visual function, increases in visual acuity from pre-treatment levels were achieved immediately after IMRT, and the absence of significant differences between PreVA and FPostVA indicates that vision was preserved in the overall sample. Furthermore, following IMRT, visual field improvements were seen in 14 eyes immediately after IMRT.

Although comparison of PreVA and IPostVA showed that IMRT was effective for all three tumor growth patterns, FPostVA of the entire sample was found to have decreased from IPostVA (Fig. 4a–c). FPostVA tended to decrease from PreVA among eyes with diffuse tumors, but it tended to increase among eyes with fusiform and globular tumors. ONSM is characterized by progressive visual loss, and although one study demonstrated that visual function prognosis is the worst in cases of diffuse tumor growth exhibiting apical expansion [3]. Other research into the prognoses of individual growth patterns is still lacking. The FPostVA findings of the present study suggest that IMRT is favorably indicated for fusiform and globular tumors. In contrast, it was difficult to reach any conclusions in terms of diffuse tumors, because the present sample was not compared with a control group undergoing natural disease progression. Therefore, the effectiveness of IMRT for treating diffuse tumors remains a priority moving forward. IMRT can be performed with high precision by adjusting to the shape of the lesion. Therefore, the difference in treatment effect among tumor growth pattern could result from the extent of the damage or preservation of the optic nerve depending on the shape of the tumors rather than the difference in the dose distribution.

With respect to optic disc findings, of the 5 eyes negative for pre-treatment optic disc abnormalities, there were significant improvements in IPostVA and field performance regardless of the degree of visual loss and visual field impairment present before IMRT; a decline in FPostVA compared with IPostVA was observed in only 1 eye in the present study. On the other hand, post-treatment visual acuity and field performance for 10 eyes with pre-treatment optociliary shunt vessels and optic disc swelling and atrophy were inconsistent and ranged from improvement to no change to deterioration. Since eyes negative for optic disc abnormalities showed only a small reduction in FPostVA (i.e., late-stage vision), we believe that early treatment with IMRT before the appearance of atrophy, swelling, and other types of optic disc insult may lead to better outcomes for visual function.

In terms of SRT for ONSM, it has been reported that no relationship exists between the timing of radiotherapy and prognosis [10], that better visual acuity performance can be gained with early treatment [11], that treatment efficacy is greater in eyes with PreVA ranging from 20/40 to 20/30 [12], and that treatment is indicated when visual acuity is ≤ 20/40 or when visual field impairment is detected [13].

Because the present study showed that treatment was effective regardless of the degree of visual loss, and FPostVA was better among eyes administered IMRT before developing optic disc impairment, we believe that early IMRT is desirable when patients experience subjectively reduced vision and visual field disturbances.

A search of the literature identified studies that examined the efficacy of IMRT for treating ONSM, and there were only 25 cases in total [7, 8, 11, 14‐18]. Furthermore, only 5 cases in total could be followed up for more than 5 years after IMRT as monotherapy [16, 18]. According to these studies, IMRT resulted in visual acuity improvement and stability in 19 eyes, no response in 3 eyes, and deterioration in 3 eyes, and it was associated with late adverse events, including lens opacification in 3 patients, dry eye in 3 patients, radiation-induced retinopathy in 2 patients with diabetes mellitus, keratitis in 2 patients, and blepharitis, otitis media with effusion, and early menopause in 1 patient each. The number of eyes examined in the present study is so far the greatest in a single institute.

Comparing different types of stereotactic irradiation techniques, SRT uses fractionated irradiation to deliver a uniform dose within the radiation field, IMRT delivers a non-uniform dose that mitigates exposure to proximal organs at risk, and stereotactic radiosurgery delivers a uniform dose within the radiation field in a single session. IMRT allows for more non-invasive treatment, because dose intensity can be modulated within the targeted field, thus lessening irradiation of surrounding tissue.

Various studies have reported the advantages of SRT for treating ONSM [19, 20], but they have also reported both ocular and systemic complications. IMRT is anticipated to achieve better local tumor control and visual improvement with a lower complication rate than conventional SRT [21, 22]. Acute complications observed in the present study disappeared soon after completion of IMRT. In terms of late complications, 1 eye developed ischemic optic neuropathy after IMRT. Although hypopituitarism after SRT for ONSM is reported [21], there were no symptoms related to this complication in the present study.

We showed the efficacy of IMRT in a large number of cases in a single facility. However, several limitations of this study should be acknowledged. First, because of the various follow-up period, the time when the final visual function was evaluated is different in each case. Second, due to the short observation period, the late complications of IMRT have not been evaluated. The longest observation period is 4 years and 9 months in this study.

There are few reports of long-term prognosis of IMRT because IMRT is a novel radiation therapy compared with conventionally fractionated stereotactic radiotherapy and conformal radiotherapy. We will continue to follow up the cases and evaluate long-term post-treatment visual function and complications in further study.

IMRT for the treatment of ONSM achieved improvement and preservation of visual function. We believe that early treatment with IMRT before the appearance of optic disc abnormalities can be more effective for improving visual function, particularly among patients with fusiform and globular growth patterns. Moreover, the risk of serious post-treatment complications is considered low.