Optimal Timing of Radiotherapy Following Gross Total or Subtotal Resection of Glioblastoma: A Real-World Assessment using the National Cancer Database

Abstract

Hesham elhalawani, neil chevli, pamela K. Allen * & caroline chung * treatment for glioblastoma (GBM) includes surgical resection and adjuvant radiotherapy (Rt) and chemotherapy. the optimal time interval between surgery and Rt remains unclear. the national cancer Database (ncDB) was queried for patients with GBM. overall survival (oS) was estimated using Kaplan-Meier and log-rank tests. Univariate (UVA) and multivariable cox regression (MVA) modeling was used to determine predictors of OS. A total of 45,942 patients were included. On MVA: younger age, female gender, black ethnicity, higher KpS, obtaining a gross total resection (GtR), MGMt promotermethylated gene status, unifocal disease, higher RT dose, and RT delay of 4-8 weeks had improved oS. patients who underwent a subtotal resection (StR) had worsened survival with Rt delay ≤4 weeks and patients with GtR had worsened survival when Rt was delayed >8 weeks. This analysis suggests that an interval of 4-8 weeks between resection and RT results in better survival. Delays >8 weeks in patients with a GtR and delays <4 weeks in patients with a STR/biopsy resulted in worse survival. This impact of time delay from surgery to Rt, in conjunction with extent of resection, should be considered in the clinical management of patients and future designs of clinical trials. Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Current standard of care treatment for patients 70 years or younger and with good performance status, per the National Comprehensive Cancer Network (NCCN), includes maximal safe surgical resection with image-verified complete resection, followed by adjuvant radiotherapy (RT) and chemotherapy 1. Several prior studies have demonstrated an improved progression-free survival with more complete surgical resections 2-6. Under the same assumption that maximum cytoreductive treatment provides benefit to patients and, given the aggressive and rapidly progressive nature of this disease, many clinicians seek to minimize the time delay between surgery and initiation of RT. However, in the modern era, there are potentially numerous factors that could delay time to initiation of RT, including: evolution of practice that incorporates molecular/genetic testing and consideration of enrollment to clinical trials that requires additional testing and even central pathology review. This study provides information about the possible clinical impact of time delays for these various reasons between surgical resection and the start of adjuvant radiation therapy for patients with GBM. The optimal time interval between surgery and the initiation of adjuvant therapy; however, remains unclear. Cancer in several non-central nervous system (CNS) sites, including head and neck cancer and breast cancer, have increased local-regional recurrence rates when adjuvant RT is delayed 7. To our knowledge, in patients with GBM, two retrospective series have indicated that a delay in initiating adjuvant therapy worsened survival 8,9 ; nine series, including a SEER ana...

Sex-specific aspects of epidemiology, molecular genetics and outcome: primary brain tumours

“… 31 A better survival was also observed for women in several large cohorts of the US NCDB in patients with a diagnosis of glioblastoma between 2004 and 2015, 7 32 33 independently of the extent of resection. 33 Improved survival in female glioblastoma patients has also been reported specifically in the elderly population using SEER data. 34 Similar results were obtained in an extensive cohort of 16’717 patients aged 65 years old or more, diagnosed from 2005 to 2011 in another US NCDB study.…”

A rapid review of evidence and recommendations from the SIOPE radiation oncology working group to help mitigate for reduced paediatric radiotherapy capacity during the COVID-19 pandemic or other crises

“…o For paediatric leukemic testicular relapse, 1. including DMG [51][52][53] (level 2). o Hypo-fractionation using 13 fractions of 3.0 Gy results in comparable overall survival rates in patients with DMG of pontine origin [51,53] (level 1) o The utility of systemic agents for newly diagnosed DMG of pontine origin remains unproven [54] (level 2) o A slightly improved outcome is observed in children who received lomustine in addition to temozolomide for subtotally-resected glioblastoma with MGMT overexpression [55] (level 2) o In adults with glioblastoma, delays >8 weeks in patients with GTR resulted in worse survival [56] (level 1) Recommendation o Hypo-fractionation using 3.0 Gy is an alternative to normofractionation to lower the treatment burden in patients with DMG of pontine origin [grade B], and for patients with HGG from non-pontine origin and unfavourable molecular profile (grade D).…”

The survival impact of significant delays between surgery and radiochemotherapy in glioblastoma patients: A retrospective analysis from a large tertiary center

“…Interestingly enough, our analysis suggests that for patients with residual disease or relapse, the time interval is a more important factor than for those with no sign of macroscopic disease at the onset of radiotherapy. The relation between residual disease and the impact of time interval has been previously observed by some of the authors [9][10][11], but each of them formed different conclusions. Based on our data, we speculate that in patients with residual disease, radiochemotherapy should be regarded as a salvage treatment and therefore initiated earlier.…”

“…Yusuf et al [27] found that a time interval of 22-42 days from surgery compared to patients that started RCT earlier was associated with a significantly reduced risk of death. Finally, a recent study by Buszek et al [11] showed that < 4 weeks' time interval negatively impacted the survival of the patients.…”