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A PHASE III RANDOMIZED CONTROLLED TRIAL OF SHORT-COURSE RADIOTHERAPY WITH OR WITHOUT CONCOMITANT AND ADJUVANT TEMOZOLOMIDE IN ELDERLY PATIENTS WITH GLIOBLASTOMA (NCIC CTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677)

ABSTRACT: BACKGROUND: The EORTC (26981-22981)/NCIC CTG (CE.3) RCT in newly diagnosed GBM showed increased survival with concomitant and adjuvant temozolomide (TMZ) added to radiotherapy (RT). Study pts were 18-71 (median 56) years; however a sub-group analysis noted a trend of decreasing benefit from the addition of TMZ with increasing age, such that for age 65-71, the hazard ratio of 0.8 did not reach statistical significance (p = 0.340). This may reflect a lack of efficacy in elderly patients, or simply be due to a lack of statistical power in this subgroup. Recent RCTs in elderly GBM found improved survival with RT compared to supportive care alone and detected non-inferiority of 40 Gy/15 vs. a 60 Gy/30 RT regimen and superior survival was noted for MGMT-methylated patients treated with TMZ alone vs RT alone. Based upon these results short-course hypofractionated RT is often recommended for elderly pts. However, whether the addition of TMZ to RT confers a survival advantage in elderly pts, particularly for those with methylated MGMT, remains unanswered. METHODS: We conducted a global randomized phase III clinical trial for patients ?65 yrs of age with histologically confirmed newly diagnosed glioblastoma, ECOG 0-2, randomized 1:1 to receive 40Gy/15 RT vs. 40Gy/15 RT with 3 weeks of concomitant temozolomide plus monthly adjuvant TMZ until progression or 12 cycles. Stratification is by centre, age (65-70, 71-75, or 76+), ECOG 0,1 vs 2, and biopsy vs resection. RESULTS: Accrual of n = 562 patients was completed Sept 19, 2013. Accrual by participating group was NCIC CTG 199, EORTC 249, TROG 97, and Japan 17 patients. Median age of randomized patients was 73 (65-90) years with 70% of patients over the age of 71. The study was powered to detect a HR of 0.75 in median OS, requiring 520 events for analysis. At the time of writing the required number of deaths had not been reached. A comprehensive analysis, including MGMT promoter methylation and QOL, is planned. CONCLUSIONS: A global cooperative group trial was completed randomizing 562 elderly patients with glioblastoma. The final results will add to our knowledge on the optimal treatment of these patients. SECONDARY CATEGORY: n/a.

SUBMITTER: MD J

PROVIDER: S-EPMC4144629 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Project description:BackgroundEarly endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer.MethodsBetween July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40-46 Gy in 20-25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5).FindingsAfter a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1.05 (95% CI 0.75-1.48; p=0.77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1.04; 95% CI 0.84-1.29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6.1%.InterpretationAdjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity.

Project description:PurposeThe survival times of glioblastoma (GB) patients after the standard therapy including safe maximal resection followed by radiotherapy plus concomitant and adjuvant temozolomide are heterogeneous. In order to define a simple, reliable method for predicting whether patients with isocitrate dehydrogenase (IDH)-wildtype GB treated with the standard therapy will be short- or long-term survivors, we analyzed the correlation of preoperative blood counts and their combined forms with progression-free survival (PFS) and overall survival (OS) in these patients.MethodsEighty-five patients with primary IDH-wildtype GB treated with the standard therapy between 2012 and 2019 were analyzed retrospectively. Cox proportional hazards models and Kaplan-Meier analysis were used to investigate the survival function of preoperative hematological parameters.ResultsPreoperative high neutrophil-to-lymphocyte ratio (NLR, >2.42), high platelet count (>236 × 109/L), and low red blood cell (RBC) count (≤4.59 × 1012/L) were independent prognostic factors for poorer OS (p = 0.030, p = 0.030, and p = 0.004, respectively). Moreover, a high NLR was an independent prognostic factor for shorter PFS (p = 0.010). We also found that, like NLR, preoperative high derived NLR (dNLR, >1.89) was of poor prognostic value for both PFS (p = 0.002) and OS (p = 0.033). A significant correlation was observed between NLR and dNLR (r = 0.88, p < 0.001), which had a similar prognostic power for OS (NLR: AUC = 0.58; 95% CI: [0.48; 0.68]; dNLR: AUC = 0.62; 95% CI: [0.51; 0.72]). Two scores, one based on preoperative platelet and RBC counts plus NLR and the other on preoperative platelet and RBC counts plus dNLR, were found to be independent prognostic factors for PFS (p = 0.006 and p = 0.002, respectively) and OS (p < 0.001 for both scores).ConclusionCheap, routinely ordered, preoperative assessments of blood markers, such as NLR, dNLR, RBC, and platelet counts, can predict the survival outcomes of patients with IDH-wildtype GB treated with the standard therapy.

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A PHASE III RANDOMIZED CONTROLLED TRIAL OF SHORT-COURSE RADIOTHERAPY WITH OR WITHOUT CONCOMITANT AND ADJUVANT TEMOZOLOMIDE IN ELDERLY PATIENTS WITH GLIOBLASTOMA (NCIC CTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677)

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