Impact of waiting time after surgery and overall time of postoperative radiochemotherapy on treatment outcome in glioblastoma multiforme

Annekatrin Seidlitz, Timo Siepmann, Steffen Löck, Tareq Juratli, Michael Baumann, Mechthild Krause

A time factor of radiooncological treatment has been demonstrated for several tumours, most prominently for head and neck squamous cell carcinoma and lung cancer. In glioblastoma multiforme studies of the impact of postoperative waiting times before initiation of radio- or radiochemotherapy were inconclusive. Moreover analysis of the impact of overall treatment time of radiochemotherapy as well as overall duration of local treatment from surgery to the end of radiochemotherapy is lacking to date. In this retrospective cohort study, we included 369 consecutive patients treated at our institution between 2001 and 2014. Inclusion criteria were histologically proven glioblastoma multiforme, age ≥ 18 years, ECOG performance status 0-2 before radiotherapy, radiotherapy or radiochemotherapy with 33 × 1.8 Gy to 59.4 Gy or with 30 × 2.0 Gy to 60 Gy. The impact of postoperative waiting time, radiation treatment time and overall duration of local treatment from surgery to the end of radiotherapy on overall (OS) and progression-free (PFS) survival were evaluated under consideration of known prognostic factors by univariate Log-rank tests and multivariate Cox-regression analysis. The majority of patients had received simultaneous and further adjuvant chemotherapy, mainly with temozolomide. Median survival time and 2-year OS were 18.0 months and 38.9 % after radiochemotherapy compared to 12.7 months and 12.6 % after radiotherapy alone. Median progression-free survival time was 7.5 months and PFS at 2 years was 14.3 % compared to 6.0 months and 3.3 %, respectively. Significant prognostic factors in multivariate analysis were age, resection status and application of simultaneous chemotherapy. No effect of the interval between surgery and adjuvant radiotherapy (median 27, range 11-112 days), radiation treatment time (median 45, range 40-71 days) and of overall time from surgery until the end of radiotherapy (median 54, range 71-154 days) on overall and progression-free survival was evident. Our data do not indicate a relevant time factor in the treatment of glioblastoma multiforme in a large contemporary single-centre cohort. Although this study was limited by its retrospective nature, its results indicate that short delays of postoperative radiochemotherapy, e.g. for screening of a patient for a clinical trial, may be uncritical.