Up to date, most studies of adult ONGs are individual case reports or only include a limited number of patients.[16–18, 20–25] The largest research, which included 445 patients, not only mixed pediatric and adult cases, but also focused on the analysis of tumors in the pediatric population. Few investigations have focused explicitly on adults ONGs.[17, 25] For all we know, this study, including 179 cases on the basis of the SEER database, is the largest series of adult ONGs and is the only study to compare the effects of different treatment strategies (including surgery, adjuvant RT, and chemotherapy) on survival with a large number of adult patients. Furthermore, our data identify that both adjuvant treatments (RT and chemotherapy) have a negative impact on the survival and prognosis of adult patients with low-grade tumors.
Epidemiological and Tumor Characteristics
ONGs in adults are extremely uncommon and were first described by Hoyt et al. in 1973, which included 15 adult patients with malignant optic glioma. In our study, 70% of the patients were below the age of 50, especially in the low-grade tumors, and the mean age at diagnosis was 42.1 years, which is nearly consistent with the previously limited reported mean age for patients diagnosed at the adulthood of 39 years. However, patients diagnosed with high-grade ONGs usually were older than those with low-grade ONGs, ranging from 57 to 66 years,[23, 18, 19] the same with our results. In addition, although other studies showed an equal ratio of male and female in the adult population,[25, 17] a female predominance was demonstrated in this large study.
In terms of treatment, gross totally surgical resection usually was not the primary treatment option in patients with ONGs, especially for low-grade at any age.[1, 19, 17] Up to 72.6% of the patients underwent no surgery in the present study. For adjuvant therapies, there were differences between low-grade and high-grade groups. The existing reported data on RT and chemotherapy in patients with low-grade ONGs are mainly limited in the pediatric population.[8, 15, 26–28] In our study, 38.7% and 11.3% of low-grade adult patients received RT and chemotherapy, respectively. However, for the high-grade group, surgery or biopsy, followed by adjuvant RT and/or chemotherapy, could be considered the standard of care,[18, 20, 22, 23, 17] and these two proportions of the adjuvant therapies in current study were 68.4% and 47.4%, respectively.
Factors Associated with Survival and Tumor Management
Gender, marital status, race, year of diagnosis, tumor site, and different surgical patterns were not critical predictors of survival in univariate and multivariate analysis. However, age at diagnosis, tumor grade, and adjuvant RT and chemotherapy were significant survival factors in adult patients with ONGs. Although age was not recognized as a prognostic factor in a previous study, our result showed that patients with age ≥ 50 years had a worse prognosis in both low- and high-grade groups, similar to other published series of gliomas.[29, 30] It is universally acknowledged that patients with low-grade gliomas have a better survival prognosis, which had a 5-year OS rate of 85.5% compared to 10.5% for patients with high-grade gliomas in our study. Furthermore, although many reported cases of adult ONGs are high-grade, we found most of them remain low-grade tumors, inconsistent with the study by Shofty et al., in which 80% of primary adult ONGs are also low-grade.
Unlike the gliomas in other sites, there is no gold standard in treating both low-grade and high-grade ONGs. The general goal of all individualized treatment strategies is to preserve the patient’s vision as long as possible. Based on this goal, surgical resection might not be a preferred option and is discouraged due to the inevitable blindness on the affected side or bilateral visual loss risks. Our current results demonstrate no significant differences among various surgical options for patients with any grade ONGs regarding OS. Therefore, initial observation is frequently recommended with ophthalmological evaluation and neuroimaging surveillance to confirm clinical stability, particularly for low-grade ONGs. However, for malignant ONGs or progressive tumors with the aggressively visual decline, it might be appropriate to consider surgical excision to debulk the tumor and obtain a pathological diagnosis before commencing the following adjuvant therapy.[7, 1, 2]
The role of adjuvant RT and chemotherapy in an adult population remains unclear due to its rarity. To our knowledge, there have been only nine documented cases of low-grade optic pathway gliomas in adults in the past few years.[17, 16] The recent case study by Hidalgo et al. demonstrated that an adult patient with low-grade optic pathway glioma who received no adjuvant therapy after STR could survive more than 20 years without tumor progression. In another study that included limited 14 children with optic chiasmatic-hypothalamic gliomas, no significant differences were observed regarding the volume change of tumors treated or not treated with chemotherapy. The critical finding in our study shows that both adjuvant RT and chemotherapy may have potentially adverse effects on survival in adult patients with low-grade ONGs. The concrete reason is unknown because of the limited clinical information included in the SEER database; however, on the grounds of some previously published studies, it is most likely attribute to the systemic side effects and increased risks of malignant progression and visual, neurocognitive and hypothalamic dysfunction after such adjuvant treatments, especially RT.[1, 2, 33–35, 26] Therefore, given the above analysis, we do not recommend to take RT or chemotherapy in adult patients with low-grade ONGs.
For high-grade ONGs in adult patients, the reported average survival ranged from 1 to 2 years, despite aggressive treatment with RT and chemotherapy, similar to that of glioblastoma in other locations.[36, 37, 23] Our results demonstrate that both adjuvant RT and chemotherapy have no positive effect on patients’ OS. Therefore, given the very limited number of reported and our cases, it can not be confirmed whether adjuvant therapies benefit the adult patient or not. Nevertheless, considering the same histopathological characteristics of high-grade gliomas located in other brain sites, a combination of adjuvant RT and chemotherapy after surgery might remain the most appropriate option that can be adopted for adult patients with ONGs at present. Indeed, large-scale collaborative multicenter prospective studies are still warranted to determine treatment consensus.
Despite the fact that a huge amount of invaluable data for rare tumors such as ONGs can be acquired in the SEER database, there are still several important limitations to the present study. First, there is no information available on visual outcomes or tumor progression, which is important to be an endpoint for assessing the effects, particularly for the low-grade group. Second, there is a lack of details on the adjuvant treatments, such as chemotherapeutic agents, dose and type of RT, and the exact time of adjuvant treatments. Third, several critical factors, including performance status, systemic disease status, NF-1 status, or neuroendocrine morbidity, are unable to obtain from the SEER database. Finally, given the impossibly pathological and radiological review of the tumors, it is likely that some tumors may have been misdiagnosed owing to the low interobserver agreement in the diagnosis of different glioneuronal tumors. However, considering the prospective studies not available and not be expected in the near future, because of the scarcity of ONGs, a large retrospective study like this seems to be the best and most useful approach available to define the role of different adjuvant treatments for these lesions. Therefore, although several limitations mentioned above, this is the largest reported series and the best evidence available in regard to adult ONGs up to date.