Survival impact of prolonged postoperative radiation therapy for patients with glioblastoma treated with combined-modality therapy (original) (raw)
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Cancer, 2020
BACKGROUND: Previous studies examining the time to initiate chemoradiation (CRT) after surgical resection of glioblastoma have been conflicting. To better define the effect that the timing of adjuvant treatment may have on outcomes, the authors examined patients within the National Cancer Database (NCDB) stratified by a validated prognostic classification system. METHODS: Patients with glioblastoma in the NCDB who underwent surgery and CRT from 2004 through 2013 were analyzed. Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (III, IV, V) was extrapolated for the cohort. Time intervals were grouped weekly, with weeks 4 to 5 serving as the reference category for analyses. Kaplan-Meier analysis, log-rank testing, and multivariate (MVA) Cox proportional hazards regression were performed. RESULTS: In total, 30,414 patients were included. RPA classes III, IV, and V contained 5250, 20,855, and 4309 patients, respectively. On MVA, no time point after week 5 was associated with a change in overall survival for the entire cohort or for any RPA class subgroup. The periods of weeks 0 to 1 (hazard ratio [HR], 1.18; 95% CI, 1.02-1.36), >1 to 2 (HR, 1.23; 95% CI, 1.16-1.31), and >2 to 3 (HR, 1.11; 95% CI, 1.07-1.15) demonstrated slightly worse overall survival (all P < .03). The detriment to early initiation was consistent across each RPA class subgroup. CONCLUSIONS: The current data provide insight into the optimal timing of CRT in patients with glioblastoma and describe RPA class-specific outcomes. In general, short delays beyond 5 weeks did not negatively affect outcomes, whereas early initiation before 3 weeks may be detrimental. Cancer 2020;0:1-10.
Journal of neurosurgery, 2015
OBJECT There are few and conflicting reports on the effects of delayed initiation of chemoradiotherapy on the survival of patients with glioblastoma. The standard of care for newly diagnosed glioblastoma is concurrent radiotherapy and temozolomide chemotherapy after maximal safe resection; however, the optimal timing of such therapy is poorly defined. Given the lack of consensus in the literature, the authors performed a retrospective analysis of The Cancer Genome Atlas (TCGA) database to investigate the effect of time from surgery to initiation of therapy on survival in newly diagnosed glioblastoma. METHODS Patients with primary glioblastoma diagnosed since 2005 and treated according to the standard of care were identified from TCGA database. Kaplan-Meier and multivariate Cox regression analyses were used to compare overall survival (OS) and progression-free survival (PFS) between groups stratified by postoperative delay to initiation of radiation treatment. RESULTS There were 218 ...
Prognostic factors for survival of patients with glioblastoma: Recursive partitioning analysis 1
2000
Survival for patients with glioblastoma multiforme is short, and current treatments provide limited benefit. Therefore, there is interest in conducting phase 2 trials of experimental treatments in newly diagnosed patients. However, this requires historical data with which to compare the experimental therapies. Knowledge of prognostic markers would also allow stratification into risk groups for phase 3 randomized trials. In this retrospective study of 832 glioblastoma multiforme patients enrolled into prospective clinical trials at the time of initial diagnosis, we evaluated several potential prognostic markers for survival to establish risk groups. Analyses were done using both Cox proportional hazards modeling and recursive partitioning analyses. Initially, patients from 8 clinical trials, 6 of which included adjuvant chemotherapy, were included. Subsequent analyses excluded trials with interstitial brachytherapy, and finally included ). 3 Abbreviations used are as follows: GBM, glioblastoma multiforme; KPS, Karnofsky performance status; RTOG, Radiation Therapy Oncology Group; RPA, recursive partitioning analysis; UCSF, University of California San Francisco.
Radiation Oncology, 2015
Background: 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. Methods: 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. Results: 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. Conclusion: 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.
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2018
We retrospectively examined the potential effect on overall survival (OS) of delaying radiotherapy to administer neoadjuvant therapy in unresected glioblastoma patients. We compared OS in 119 patients receiving neoadjuvant therapy followed by standard treatment (NA group) and 96 patients receiving standard treatment without neoadjuvant therapy (NoNA group). The MaxStat package of R identified the optimal cut-off point for waiting time to radiotherapy. OS was similar in the NA and NoNA groups. Median waiting time to radiotherapy after surgery was 13 weeks for the NA group and 4.2 weeks for the NoNA group. The longest OS was attained by patients who started radiotherapy after 12 weeks and the shortest by patients who started radiotherapy within 4 weeks (12.3 vs 6.6 months) (P = 0.05). OS was 6.6 months for patients who started radiotherapy before the optimal cutoff of 6.43 weeks and 19.1 months for those who started after this time (P = 0.005). Patients who completed radiotherapy had ...
International Journal of Radiation Oncology*Biology*Physics, 1999
Purpose: Three databases were pooled and analyzed to determine which groupings of prognostic factors best predicted overall survival for patients with low-grade gliomas treated with surgery and immediate or delayed radiotherapy. Methods and Materials: Databases of patients with low-grade gliomas compiled at the London Regional Cancer Centre (LRCC), the Norwegian Radium Hospital (NRH), and the University of California, San Francisco (UCSF) were merged. Inclusion criteria for the pooled analysis included: age > 18 years and histologically confirmed low-grade (World Health Organization Grade II) supratentorial fibrillary astrocytoma, oligodendroglioma or mixed oligoastrocytoma. Factors analyzed for prognostic significance included: age at diagnosis, gender, seizures at presentation, presence of enhancement on computed tomography (CT) or magnetic resonance imaging (MRI), Karnofsky Performance Status (KPS) at diagnosis, histology, extent of surgical resection, timing of radiotherapy, and treating institution. Univariate and multivariate analysis of overall survival for these factors was performed. Recursive partitioning was performed to generate prognostic groups using these factors.
Neuro-Oncology, 2012
We explored the feasibility of concurrent palliative chemotherapy and low-dose fractionated radiotherapy (LD-FRT) in glioblastoma multiforme (GBM). Patients with recurrent/progressive GBM at least 3 months after the end of primary radiotherapy received 0.3 Gy twice daily with cisplatin and fotemustine if progressing on temozolomide, or 0.4 Gy twice daily with temozolomide if recurrent 4-6 months later (retreatment group). Newly diagnosed GBM with gross residual mass received 30 Gy with concomitant and adjuvant temozolomide and 0.4 Gy twice daily from the second adjuvant cycle (naive group) for 2-4 cycles. Twenty-six patients were enrolled. In the retreatment group (n 5 17; median LD-FRT total dose 7.2 Gy [range 2.4 -11.6]), grade 3 or 4 hematological toxicity was observed in 5.9% of patients. Median follow-up time was 20 months (range 4-35). Median progression-free survival (PFS) and overall survival (OS) from the time of recurrence or progression were 4 and 8 months, respectively (OS at 6 months, 69%; at 12 months, 16.7%). In the naive group (n 5 9; median LD-FRT total dose 8 Gy [range 3.2 -16]), grade 3 or 4 hematological toxicity was observed in 11.1% of patients. Median follow-up time was 17 months (range 8-20)-median PFS was 9 months, with PFS at 6 months and at 1 year of 66.7% and 26.7%, respectively; and median OS was 12 months, with OS at 6 months and at 1 year of 77.8% and 34.6%, respectively. LD-FRT with concurrent chemotherapy was well tolerated.
Journal of Neuro-oncology, 1990
The standard 6 week course of post-operative radiotherapy for glioblastoma multiforme (astrocytoma grade IV) is lengthy, considering the poor prognosis. The standard schedule is especially unsuitable for hospitalized patients and for those with poor prognostic factors (such as old age and poor performance status) since their survival is particularly short. In order to improve the survival — treatment time ratio, we entered a total of 14 hospitalized patients with glioblastoma multiforme (GBM) and poor prognostic factors (mean age 62, mean KPS 57 %) into a Phase I trial of accelerated fractionation (AF) external beam radiotherapy. A total tumor dose of 5400–5500 cGy was given in 3 weeks: 4300–4500 cGy whole brain using 100 cGy tid fractions on weekdays plus a 900–1200 cGy boost using single daily fractions of 150–200 cGy on weekends. Only one patient entered did not complete therapy, due to the development of pulmonary embolism resulting in death. Mean survival for all 14 patients from the time of surgical diagnosis was 30.4 weeks. The schedule was well tolerated and resulted in a substantial decrease in treatment time compared to conventional fractionation in these patients. AF schedules should continue to be explored since they may be more appropriate than conventional fractionation schedules for GBM patients with poor prognostic factors, particularly when hospitalized.
Survival improvements with adjuvant therapy in patients with glioblastoma
ANZ Journal of Surgery, 2017
BackgroundEvaluate survival of patients diagnosed with glioblastoma multiforme (GBM) managed with adjuvant intensity modulated radiation therapy and temozolomide since the introduction of the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC‐NCIC) protocol.MethodsAll patients with GBM managed between May 2007 and December 2014 with EORTC‐NCIC protocol were entered into a prospective database. The primary endpoint was the median survival. Univariate predictors of survival were evaluated with respect to tumour resection, age and Eastern Cooperative Oncology Group (ECOG) performance status using log‐rank comparisons.ResultsTwo hundred and thirty‐three patients were managed under the protocol and analysed for outcome. The median age was 57 years; the rate of gross total resection, subtotal resection and biopsy were 47.2%, 35.2% and 17.6%, respectively. At progression, 49 patients had re‐resection, and in addit...