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Randomized Controlled Trial
. 2015 Jul;17(7):999-1006.
doi: 10.1093/neuonc/nov009. Epub 2015 Feb 16.

Variation over time and interdependence between disease progression and death among patients with glioblastoma on RTOG 0525

Meihua Wang  1 , James J Dignam  1 , Minhee Won  1 , Walter Curran  1 , Minesh Mehta  1 , Mark R Gilbert  1
Affiliations
Randomized Controlled Trial

Variation over time and interdependence between disease progression and death among patients with glioblastoma on RTOG 0525

Meihua Wang et al. Neuro Oncol. 2015 Jul.

Abstract

Background: We assessed the longitudinal hazard characteristics for death and progression in patients with glioblastoma, evaluated the impact of prognostic factors and treatment on the hazard within different time intervals to determine if effects are time varying, and quantified the influence of progression on survival.

Methods: Among patients randomized to Radiation Therapy Oncology Group trial 0525, which compared dose-dense with standard-dose temozolomide, we estimated the hazards of death and treatment failure (death or progression) over time and their interdependence.

Results: The peak hazard of death was reached at around 16 months with a slow decline after that; the hazard of progression/death reached a peak at around 6 months and decreased dramatically thereafter. The survival advantages for patients with MGMT gene promoter methylation and recursive partitioning analysis class III were substantial in the first 2 years, but lessened thereafter. The progression-free survival benefit of dose-dense over standard-dose temozolomide occurred in the first 6 months (hazard ratio: 0.70; 95% CI: 0.58-0.86; P < .001), although it diminished thereafter. After adjusting for recursive partitioning analysis class and MGMT methylation status, the hazard ratio of death for patients who had progressed over nonprogressors was 6.59 (95% CI: 5.15-8.43; P < .001).

Conclusion: After the peak hazard of death, a consistently high hazard remains, but it is lower than in the peak period. The progression hazard peak is earlier, and then hazard consistently declines. The rate of dying after disease progression is about 6.59 times the rate for nonprogressors, suggesting that progression-free survival may be a relevant clinical endpoint.

Keywords: glioblastoma; hazard of death; hazard of failure (progression or death).

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Figures

Fig. 1.
Fig. 1.
OS and death hazard over time.
Fig. 2.
Fig. 2.
PFS and failure hazard over time.
Fig. 3.
Fig. 3.
Hazard by treatment for MGMT methylated and unmethylated subsets.
Fig. 4.
Fig. 4.
Relationship between progression and survival.
See this image and copyright information in PMC

References

    1. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004–2007. Source: Central Brain Tumor Registry of the United States, Hinsdale, IL: website: www.cbtrus.org; 2011.
    1. Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008;3595:492–507. - PubMed
    1. Gilbert M, Wang M, Aldape K, et al. Dose dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013;31(32):4085–4091. - PMC - PubMed
    1. Lawless J. Statistical Models and Methods for Lifetime Data. New York: Wiley; 1982.
    1. Aalen O, Gjessing H. Understanding the shape of the hazard rate: a process point of view. Stat Sci. 2011;16(1):1–22.

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