Clinical and economic evaluation of modulated electrohyperthermia concurrent to dose-dense temozolomide 21/28 days regimen in the treatment of recurrent glioblastoma: a retrospective analysis of a two-centre German cohort trial with systematic comparison and effect-to-treatment analysis

BMJ Open. 2017 Nov 3;7(11):e017387. doi: 10.1136/bmjopen-2017-017387.


Objective: To assess the efficacy and cost-effectiveness of modulated electrohyperthermia (mEHT) concurrent to dose-dense temozolomide (ddTMZ) 21/28 days regimen versus ddTMZ 21/28 days alone in patients with recurrent glioblastoma (GBM).

Design: A cohort of 54 patients with recurrent GBM treated with ddTMZ+mEHT in 2000-2005 was systematically retrospectively compared with five pooled ddTMZ 21/28 days cohorts (114 patients) enrolled in 2008-2013.

Results: The ddTMZ+mEHT cohort had a not significantly improved mean survival time (mST) versus the comparator (p=0.531) after a significantly less mean number of cycles (1.56 vs 3.98, p<0.001). Effect-to-treatment analysis (ETA) suggests that mEHT significantly enhances the efficacy of the ddTMZ 21/28 days regimen (p=0.011), with significantly less toxicity (no grade III-IV toxicity vs 45%-92%, p<0.0001). An estimated maximal attainable median survival time is 10.10 months (9.10-11.10). Cost-effectiveness analysis suggests that, unlike ddTMZ 21/28 days alone, ddTMZ+mEHT is cost-effective versus the applicable cost-effectiveness thresholds €US$25 000-50 000/quality-adjusted life year (QALY). Budget impact analysis suggests a significant saving of €8 577 947/$11 201 761 with 29.1-38.5 QALY gained per 1000 patients per year. Cost-benefit analysis suggests that mEHT is profitable and will generate revenues between €3 124 574 and $6 458 400, with a total economic effect (saving+revenues) of €5 700 034 to $8 237 432 per mEHT device over an 8-year period.

Conclusions: Our ETA suggests that mEHT significantly improves survival of patients receiving the ddTMZ 21/28 days regimen. Economic evaluation suggests that ddTMZ+mEHT is cost-effective, budget-saving and profitable. After confirmation of the results, mEHT could be recommended for the treatment of recurrent GBM as a cost-effective enhancer of ddTMZ regimens, and, probably, of the regular 5/28 days regimen. mEHT is applicable also as a single treatment if chemotherapy is impossible, and as a salvage treatment after the failure of chemotherapy.

Keywords: cost-effectiveness analysis; dose-dense temozolamide (ddtmz; effect-to-treatment analysis (eta); modulated electro-hyperthermia (meht); oncothermia; recurrent glioblastoma.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / economics
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Brain Neoplasms / economics
  • Brain Neoplasms / therapy*
  • Cost-Benefit Analysis
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / economics
  • Dacarbazine / therapeutic use
  • Female
  • Germany
  • Glioblastoma / economics
  • Glioblastoma / therapy*
  • Humans
  • Hyperthermia, Induced / economics*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / therapy
  • Quality-Adjusted Life Years
  • Regression Analysis
  • Retrospective Studies
  • Temozolomide


  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide