Reirradiation of High-Grade Gliomas: A Retrospective Analysis of 198 Patients Based on the Charité Data Set

Abstract

Purpose There is no standard of care for recurrent high-grade glioma. Treatment strategies include reresection, reirradiation, systemic agents, intratumoral thermotherapy using magnetic iron-oxide nanoparticles (“nanotherapy”), and tumor treating fields. Only a small number of patients are eligible for reresection, and because many patients receive a full course of radiation therapy, there is fear of reirradiation-induced morbidity. Modern radiation techniques have resulted in greater acceptance of reirradiation. In this work we retrospectively analyzed patients who had undergone reirradiation of high-grade glioma at Charité Universitätsmedizin Berlin. Methods and Materials All patients treated with reirradiation for recurrent high-grade glioma in our department from January 1997 to February 2014 were analyzed in this study. In total, 198 patients were included. The primary endpoint was overall survival after recurrence. Results One hundred ninety-eight patients were identified. Median time from first radiation therapy to reirradiation was 14 months. Median follow-up from the first day of reirradiation to last contact or death was 7 months. Median overall survival after relapse was 7 months for the overall cohort. For glioblastoma, median overall survival after relapse was 6 months and for grade 3 gliomas 14 months. Treatment was generally well tolerated. Common Terminology Criteria for Adverse Events grade 3 toxicity was observed in 5.1% patients and grade 4 toxicity in 2.5%. No patient developed grade 5 toxicity. The likelihood of developing severe toxicity (Common Terminology Criteria for Adverse Events grade 3 or 4) was not significantly higher in the group of patients who received reirradiation in the first 14 months after initial radiation therapy. Patients who received a higher biologically effective dose to the tumor also did not have a significantly higher rate of severe acute toxicity. Conclusions The prognosis of recurrent high-grade glioma remains dismal. Reirradiation is often tolerable even after early recurrence (<14 months) and with higher doses (eg, 49.4 Gy/3.8 Gy) in selected patients.

Current status and recent advances in reirradiation of glioblastoma

“…Concomitant and/or adjuvant treatment with temozolomide has resulted in longer overall survival and progression-free survival times compared with radiation alone, but this is generally limited to MGMT methylated tumors [ 13 , 48 , 63 , 72 ]; in addition, no clear survival advantages have been observed by other authors [ 58 , 74 , 85 ]. Some studies suggested significantly longer survival with the addition of bevacizumab to both SRS and fractionated SRT compared to reirradiation alone [ 38 , 50 , 52 , 76 , 78 ]; in contrast, other studies failed to demonstrate survival advantages [ 30 , 68 , 69 , 85 ]. Overall, the different prognostic impact of chemoradiation over radiation alone in patients with recurrent GBM remains to determined in prospective trials.…”

“…Hypofractionated SRT with or without systemic therapy has been frequently used in the setting of recurrent GBM. Treatments include moderately (generally 2.5–3.5 Gy per fraction) and high-dose (5 Gy or more per fraction) hypofractionated schedules (Table 2 ) [ 12 , 13 , 55 – 69 ]. Because of its higher degree of precise patient positioning and accurate dose delivery, SRT has superseded conventional RT in clinical practice in the last two decades for the treatment of patients with recurrent tumors.…”

“…Several prognostic factors have been correlated with clinical outcomes following reirradiation in patients with GBM. Age at reirradiation, Karnofsky performance status (KPS), tumor grade (grade III versus grade IV glioma) are well recognized prognostic factors associated with longer survival, whereas the role of other factors, including tumor volume, surgery before reirradiation, time interval from first course of RT, use of concurrent systemic therapy, and MGMT promoter methylation remains controversial [ 43 , 54 , 56 – 58 , 64 , 69 , 71 , 74 , 75 , 80 – 85 ]. In this regard, some, but not all, studies failed to demonstrate the favorable impact of surgery before reirradiation [ 57 , 80 , 82 , 84 , 93 ] and time interval between initial standard chemoradiation and reirradiation [ 56 , 58 , 64 , 75 , 81 , 82 , 85 ]; however, the majority of authors suggest a minimum interval of six month-interval between the two radiation courses.…”

CyberKnife for Recurrent Malignant Gliomas: A Systematic Review and Meta-Analysis

“…Possible treatment strategies for recurrent malignant gliomas (rMGs) include second-line CMTs, surgery with or without adjuvant therapies, and RT ( 2 , 6 , 7 ). Reirradiation appears to be an efficacious and safe treatment modality, providing survival benefits with acceptable risk ( 8 , 9 ). Among different reirradiation modalities, hypofractionated stereotactic radiotherapy (HFSRT) has shown promising results as it allows delivery of a large total dose, in a precise target volume and short treatment duration ( 10 , 11 ).…”