Impact of delays in initiating postoperative chemoradiation while determining the MGMT promoter-methylation statuses of patients with primary glioblastoma

BMC Cancer. 2015 Jul 30:15:558. doi: 10.1186/s12885-015-1545-x.

Abstract

Background: The benefits of new innovations in glioblastoma therapies should not be curtailed as a result of delays in commencement of radiation therapy, caused by clinical circumstances as well as diagnostic procedures. This study evaluates whether delays in chemo-radiotherapy after surgery, while determining O6-methylguanine-DNA-methyltransferase (MGMT) promoter status, affect the survival rates of patients with glioblastoma (GBM).

Methods: Our sample comprised 50 GBM patients in a retrospective analysis of three prospective studies that focused on combined radiotherapy and required MGMT promoter-status testing as inclusion criteria. Results were compared with a reference group of 127 favourable GBM cases (Karnofsky performance-status scale ≥ 70), in which the patients underwent standard postoperative chemo-radiotherapy with temozolomide. Survival time was calculated using the Kaplan-Meier method, and a multivariate analysis of the delays between surgical and radiotherapy procedures was performed using the Cox regression model.

Results: The study group's median overall survival time was 16.2 months (with a range of 2 to 56 months), versus the reference group's survival time of 18.2 months (with a range of 1 to 92 months) (p = 0.64). The delay between surgery and radiotherapy was increased by 8 days in the study patients (p < 0.001), with a median delay of 35 days (range: 18-49 days) corresponding to the typical 27-day delay (range: 5-98 days) for those in the reference group. Univariate and multivariate analyses did not show any negative association between survival time and delaying radiation therapy to determine MGMT-promoter status; commencement of radiation therapy sooner than 24 days after surgery was the threshold for significantly decreased overall survival (p = 0.01) and progression-free (p = 0.03) survival.

Conclusion: Delaying postoperative chemoradiation for GBM patients--carried out in order to determine MGMT-promoter status-did not have a negative impact on survival time. Indeed, the data of the present study shows that initiating radiation therapy sooner than 24 days after surgery has a negative impact on progression and survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chemoradiotherapy / methods*
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Female
  • Glioblastoma / genetics*
  • Glioblastoma / therapy*
  • Humans
  • Male
  • Middle Aged
  • Postoperative Care
  • Promoter Regions, Genetic
  • Retrospective Studies
  • Survival Analysis
  • Temozolomide
  • Tumor Suppressor Proteins / genetics*
  • Young Adult

Substances

  • Tumor Suppressor Proteins
  • Dacarbazine
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide