Dataset Information

Detecting overall survival benefit derived from survival postprogression rather than progression-free survival.

ABSTRACT: Broglio and Berry (2009) examined the impact of survival postprogression (SPP) on overall survival (OS) when progression-free survival (PFS) was used to assess treatment effect in metastatic cancer. Their simulation studies found no statistical difference in OS because of dilution effect from SPP, although there was a statistical difference in PFS between treatment arms. Recently, two phase III clinical trials showed efficacy of experimental treatments in OS, but not PFS. These results seem counterintuitive, because it may be reasonable to consider that the effect of treatment in prolonging PFS can influence OS prolongation. We conducted simulations to examine the role of SPP in OS under the assumption that only SPP, and not PFS, differed between treatment arms. We also explored the impact of patient heterogeneity on the OS analysis. Our study offers a reasonable explanation for the two phase III trials and recommends further discussion of PFS as an adequate endpoint and what role SPP might play in OS to evaluate current treatment regimens.

SUBMITTER: Morita S

PROVIDER: S-EPMC4609552 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Detecting overall survival benefit derived from survival postprogression rather than progression-free survival.

Morita Satoshi S Sakamaki Kentaro K Yin Guosheng G

Journal of the National Cancer Institute 20150508 8

Broglio and Berry (2009) examined the impact of survival postprogression (SPP) on overall survival (OS) when progression-free survival (PFS) was used to assess treatment effect in metastatic cancer. Their simulation studies found no statistical difference in OS because of dilution effect from SPP, although there was a statistical difference in PFS between treatment arms. Recently, two phase III clinical trials showed efficacy of experimental treatments in OS, but not PFS. These results seem coun ...[more]

PMID: 25956357

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Project description:BackgroundSupratotal resection is advocated in lower-grade gliomas (LGGs) based on theoretical advantages but with limited verification of functional risk and data on oncological outcomes. We assessed the association of supratotal resection in molecularly defined LGGs with oncological outcomes.MethodsIncluded were 460 presumptive LGGs; 404 resected; 347 were LGGs, 319 isocitrate dehydrogenase (IDH)-mutated, 28 wildtype. All patients had clinical, imaging, and molecular data. Resection aimed at supratotal resection without any patient or tumor a priori selection. The association of extent of resection (EOR), categorized on volumetric fluid attenuated inversion recovery images as residual tumor volume, along with postsurgical management with progression-free survival (PFS), malignant (M)PFS, and overall survival (OS) assessed by univariate, multivariate, and propensity score analysis. The study mainly focused on IDH-mutated LGGs, the "typical LGGs."ResultsMedian follow-up was 6.8 years (interquartile range, 5-8). Out of 319 IDH-mutated LGGs, 190 (59.6%) progressed, median PFS: 4.7 years (95% CI: 4-5.3). Total and supratotal resection obtained in 39% and 35% of patients with IDH1-mutated tumors. In IDH-mutated tumors, most patients in the partial/subtotal group progressed, 82.4% in total, only 6 (5.4%) in supratotal. Median PFS was 29 months (95% CI: 25-36) in subtotal, 46 months (95% CI: 38-48) in total, while at 92 months, PFS in supratotal was 94.0%. There was no association with molecular subtypes and grade. At random forest analysis, PFS strongly associated with EOR, radiotherapy, and previous treatment. In the propensity score analysis, EOR associated with PFS (hazard ratio, 0.03; 95% CI: 0.01-0.13). MPFS occurred in 32.1% of subtotal total groups; 1 event in supratotal. EOR, grade III, previous treatment correlated to MPFS. At random forest analysis, OS associated with EOR as well.ConclusionsSupratotal resection strongly associated with PFS, MPFS, and OS in LGGs, regardless of molecular subtypes and grade, right from the beginning of clinical presentation.

Dataset Information

Detecting overall survival benefit derived from survival postprogression rather than progression-free survival.

Publications

Detecting overall survival benefit derived from survival postprogression rather than progression-free survival.

Similar Datasets

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