Gliomas are the most common malignant tumors of the central nervous system, accounting for ~50% of all intracranial tumors. Gliomas are often located in functional areas exhibiting invasive growth and leading to progressive deterioration; also recurrences are common (1). Treatments for glioma include surgery, radiotherapy, chemotherapy, molecular biology approaches and gene therapy, with surgery being the most common approach. However, complete removal is hard to achieve, resulting in common unsatisfactory outcomes and a high recurrence rate (2). The survival time of patients with recurrent glioma is usually short. Without timely treatment, survival time is usually shorter than 6 months. In addition, the life quality of patients is usually poor. Therefore, recurrent gliomas present an ongoing challenge for the treatment of neurological diseases (3). Although in vitro radiotherapy can effectively kill glioma tumor cells, it can also bring damage to surrounding healthy brain tissue, skin and scalp, and the amount of collateral damage increases with higher doses. In all, the development of a novel treatment that can effectively kill tumor cells and improve outcomes, while reducing the side effects of radiation treatment is urgently needed (4,5). ¹²⁵I seed implantation is a kind of in vivo radiotherapy. ¹²⁵I seed implantation achieves low dose continuous exposure, high accuracy and killing of tumor cells in short-range (6). In this study, patients with recurrent glioma were treated with surgery combined with ¹²⁵I seed implantation, and their prognosis was analyzed. Our study provides scientific evidence for the effectiveness of this treatment.

General information: Sixty-six patients with recurrent gliomas were selected in Yidu Central Hospital of Weifang from April, 2011 to March, 2014. Patients were randomly divided into a surgery alone (control) group and a surgery combined with ¹²⁵I seed implantation (observation) group, with 33 patients in each. The presence of a malignant glioma diagnosed by pathological examination, with recurrent tumor diagnosed by head MRI, measurable lesions and an expected survival longer than 8 weeks were all characteristics of the inclusion criteria for the patients. Additionally, all signed informed consent forms. Patients excluded from the study were those with severe uncontrollable hypertension, transient ischemic attack, shock or cerebral hemorrhage; patients with severe coagulation dysfunction; and patients with a preoperative Karnofsky Performance Status (KPS) score lower than 50 points. There were no significant differences in the general information of patients between the two groups (P>0.05) (Table I).

The treatment efficacies in the two groups were compared at 3 months after surgery. The results showed that ORR and DCR in the observation group (69.69 and 93.94%, respectively) were higher than those in the control group (42.42 and 69.69%, respectively), and the differences were statistically significant (P<0.05) (Table III).

The occurrence of adverse reactions within 1 month after surgery was compared between the two groups, no significant differences in adverse reactions were found between the groups (Table IV).

The postoperative KPS score was compared between the two groups. The results showed that the KPS scores in the observation group were significantly higher than those in the control group at 6, 12 and 18 months after operation (P<0.05) (Table V).

The survival of patients in the two groups was also compared. Results showed that the mean survival time was longer and the postoperative survival rate was higher in the observation group when compared to the same parameters in the control group (P<0.05) (Table VI and Fig. 1).

The Kaplan-Meier analysis showed that the survival time was significantly longer in the observation group compared to that in the control group (P<0.05).

The univariate analysis performed by a log-rank test showed that preoperative KPS score, tumor site, tumor pathological grade and degree of tumor resection were all adverse factors influencing the prognosis of the patients (P<0.05) (Table VII).

The multivariate Cox regression analysis for prognosis showed that preoperative KPS score, tumor pathological grade and degree of tumor resection were all independent risk factors of prognosis (P<0.05) (Table VIII).

Gliomas usually develop deep within the brain. These tumors usually cause poor life quality and show invasive growth and characteristics leading to high mortality rates like rapid progression and a low curing rate (9). Clinical manifestations of glioma include malignant vomiting, headaches, optic disc edema, neurological deficits, psychological changes, hemiplegia and ataxia, and invasion and distant metastasis can easily occur (10). Surgery is the preferred treatment for gliomas. However, gliomas can frequently recur within 6–10 months after surgery. Once recurrence has happened, neurological damage in patients increases, the area of the nerve structures damaged is enlarged, and short-term decline in the level of awareness ensues, eventually leading to brain failure and death (11). The main reason for recurrence is the existence of glioma cell infiltration around the primary tumor, and most of the recurrent lesions are found in an area within 2 cm around the tumor, so control of local recurrence is essential for treatment of malignant gliomas (12).

Treatment of recurrent gliomas requires secondary surgery or chemotherapy and radiotherapy. However, the blood-brain barrier increases difficulties in delivering drugs to brain, so chemotherapy drugs cannot be used to effectively treat gliomas. In addition, chemotherapy is usually accompanied by severe adverse side effects, seriously affecting life quality of the patients (13). Radiation therapy can be used to reduce the size of the tumor through ionization, which in turn alleviates the symptoms and extends the survival time of patient (14). However, before reaching tumor tissues, radiation will first bring damage to surrounding brain tissue and subcutaneous structures, and this damage can be increased with the increase in radiation dose (15).

Seed implantation therapy is a new type of brachytherapy, and is also called interstitial brachytherapy. Based on the inverse square law, the radiation dose is reduced substantially with distance from the source. Energy release can usually reach 80% of its total within the area 1 cm round the seed implant, and tumor cells within this range can be effectively killed, while the damage to normal cells within this area is reduced due to the rapid decline in dose (16,17). The results of this study showed the effective rate of treatment in the observation group was significantly higher than that in the control group at 6 months after operation (P<0.05), but no significant differences in adverse reactions were found between the groups (P>0.05). The KPS scores in the observation group were significantly higher than those in the control group at 6, 12 and 18 months after operation (P<0.05), the reason probably being that the half-life of the ¹²⁵I seed is 59.4 day, providing effective radiation for four half-lives, and releasing low-energy radiation to kill tumor cells, which improves outcomes (17). Moreover, the dose distribution is more uniform in seed implantation treatment compared with other treatments, so infections caused by surgery can be reduced without inducing significant increase in normal brain tissue damage (17). The ¹²⁵I seed can provide 240 days of continuous irradiation, so that the treatment effect can last longer. Therefore, symptoms of patients can be effectively alleviated and life quality can be significantly improved (16).

Surgical treatment of recurrent gliomas requires maximum resection of tumoral tissues sparing important cortical functional areas (18). Seed implantation should be combined with MRI, to ensure optimal placement, the implanted particles should show triangle or square shape (19). In order to avoid the shedding of ¹²⁵I seed and hemorrhages, the seed should be fixed in position with a gelatin sponge. The puncture point should be treated with hemostatic treatment, and there should be constant monitoring to detect internal bleeding.

This study included analyses of prognostic factors. Multivariate Cox regression showed that preoperative KPS scores, tumor pathological grade and degree of tumor resection were independent risk factors of prognosis (P<0.05). All those three factors can affect the patient's neurological status. Life quality of patients with recurrent glioma is clinically reflected in their KPS score, and KPS scoring is an important part of prognosis prediction providing importance guidance. The median survival time of patients with KPS scores ≥70 was significantly higher than that of patients with KPS scores <70. This is because tumor metastasis and invasion can be indirectly evaluated by the KPS score. The degree of tumor resection can affect the depth and location of ¹²⁵I seed implantation, resulting in better efficacies when resection is highly successful so that the inhibitory effect of ¹²⁵I seed implantation is optimal. Also, the survival rate of recurrent gliomas is decreased with the increase of pathological grade, which is consistent with the results of case studies world-wide, meaning that pathological grade is a risk factor of prognosis (20).

We are aware of the limitations of our study due to the small sample size, so larger studies are needed. Nevertheless, based on our findings, surgery combined with ¹²⁵I seed implantation can effectively inhibit the growth of recurrent gliomas, improve the patient's condition, delay the recurrence of the tumors, and extend the survival time.