Delay in radiotherapy shortens survival in patients with high grade glioma

Irwin, Chris; Hunn, Martin; Purdie, Gordon; Hamilton, David A.

doi:10.1007/s11060-007-9426-z

Cited by 104 publications

(92 citation statements)

References 11 publications

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“…While most of these studies showed that delay of radiation therapy had no effect on survival, 1,4,9,10 a single study by Irwin et al showed that the risk of death (HR) increased by 8.9% for every week of delay to initiation of radiotherapy. 7 In contrast, however, Blumenthal et al not only found that delay was not associated with worse survival, but that the longest delayed group had the best OS.…”

Section: Discussionmentioning

confidence: 94%

Survival impact of time to initiation of chemoradiotherapy after resection of newly diagnosed glioblastoma

Sun

Ivan

et al. 2015

JNS

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Randomized clinical trials have established the efficacy of radiation and temozolomide chemotherapy for newly diagnosed glioblastoma.14,15 The standard of care for newly diagnosed glioblastoma consists of maximum safe resection of the tumor followed by radiotherapy and concurrent temozolomide based on the results of a randomized Phase III trial reported by Stupp and colleagues in 2005. 15 However, there is a paucity of data on the appropriate timing of chemoradiotherapy after surgery. The Stupp trial included patients who initiated therapy ranging from 1.7 to 10.7 weeks after diagnosis, with a median delay of 5 weeks. 15Given the aggressive nature of glioblastoma, radiotherapy and temozolomide are often recommended to start at the shortest safe interval following resection. A window of 2-3 weeks following surgery is considered ideal, alabbreviatioNs CI = confidence interval; HR = hazard ratio; KPS = Karnofsky Performance Scale; OS = overall survival; PFS = progression-free survival; TCGA = The Cancer Genome Atlas. 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 patients with newly diagnosed glioblastoma with known time to initiation of radiotherapy identified in the database. The median duration until therapy was 27 days. Delay to radiotherapy longer than the median was not associated with worse PFS (HR = 0.918, p = 0.680) or OS (HR = 1.135, p = 0.595) in multivariate analysis when controlling for age, sex, KPS score, and adjuvant chemotherapy. Patients in the highest and lowest quartiles for delay to therapy (≤ 20 days vs ≥ 36 days) did not statistically differ in PFS (p = 0.667) or OS (p = 0.124). The small subset of patients with particularly long delays (> 42 days) demonstrated worse OS (HR = 1.835, p = 0.019), but not PFS (p = 0.74). coNclusioNs Modest delay in initiation of postoperative chemotherapy and radiation does not appear to be associated with worse PFS or OS in patients with newly diagnosed glioblastoma, while significant delay longer than 6 weeks may be associated with worse OS.

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Section: Discussionmentioning

confidence: 94%

Survival impact of time to initiation of chemoradiotherapy after resection of newly diagnosed glioblastoma

Sun

Ivan

et al. 2015

JNS

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“…Radical resection in this context is either the surgeons own judgment of per operative radicality or based on radiology, the latter being more sensitive, especially when mRi has been used [10]. The data on high-grade and lowgrade gliomas show a slight increase during recent years, while surgical radicality for meningiomas has been essentially constant.…”

Section: Surgery and Postoperative Radiologymentioning

confidence: 99%

“…By experience, radiological radicality is often more sensitive than the peroperative judgment, and postoperative mRi (within 72 hours) is more sensitive than postoperative CT. The increased use of mRi is encouraging because of its higher sensitivity for brain tumor diagnostics [10]. Postoperative mRi has been the routine in the northern region and the Uppsala region, while the South-eastern region has only recently adopted early postoperative imaging, and this might explain the difference in surgical categorization.…”

Section: Surgery and Radiologymentioning

confidence: 99%

Brain tumors in Sweden: Data from a population-based registry 1999–2012

et al. 2014

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background. The Swedish brain tumor registry has, since it was launched in 1999, provided significant amounts of data on histopathological diagnoses and on important aspects of surgical and medical management of these patients. The purpose is mainly quality control, but also as a resource for research. Methods. Three Swedish healthcare regions, constituting 40% of the Swedish population, have had an almost complete registration. The following parameters are registered: diagnosis according to SNOMED/WHO classification, symptoms, performance status, pre-and postoperative radiology, tumor size and localization, extent of surgery and occurrence of postoperative complications, postoperative treatment, such as radiotherapy and/or chemotherapy, other treatments, complications and toxicity, occurrence of reoperation/s, participation in clinical trials, multidisciplinary conferences and availability of a contact nurse. results. Surgical radicality has been essentially constant, whereas the use of early (within 72 hours) postoperative CT and MRI has increased, especially for high-grade glioma, which is a reflection of quality of surgery. Survival of patients with high-grade glioma has increased, especially in the age group 60-69. Patients aged 18-39 years had a five-year survival of 40%. Waiting times for the pathological report has been slightly prolonged. Geographical differences do exist for some of the variables. conclusion. Population-based registration is valuable for assessment of clinical management, which could have impact on patient care. As a result of short survival and/or the propensity to affect cognitive functions this patient group has considerable difficulties to make their voices heard in society. We therefore believe that a report like the present one can contribute to the spread of knowledge and increase the awareness for this patient group among caregivers and policy makers.

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“…Irwin et al retrospectively analyzed the time from surgery to the initiation of RT in 172 patients from 1993 to 2003. 11 They found a mean wait time of 35 days based on multivariate analysis, which was significantly associated with survival with an 8.9% increase in the risk of death per additional week of delay in RT. These results were similar to those of burnet et al, who developed a mathematical model for analyzing the data of patients with glioblastoma and found that delayed RT led to a negative prognosis.…”

Section: Discussionmentioning

confidence: 96%

“…The addition of RT to treatment protocols in three randomized phase III trials demonstrated an approximate doubling of survival and has been the considered standard of care since the late 1970's. [6][7][8] The standard time for RT for most patients is between two and six weeks following surgery 6,[9][10][11][12] ; however, in certain resource-limited centers, it may be as long as…”

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confidence: 99%

The Potential Impact of Delayed Radiation Therapy on Patients with Glioblastoma

Alnaami

VanderPluym

Murtha

et al. 2013

Can. J. Neurol. Sci.

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790Glioblastoma is the most prevalent and aggressive primary malignant brain tumor in adults.1 Since the publication of Stupp et al., the standard of care for the treatment of glioblastoma includes maximal surgical resection followed by radiation therapy (RT) and concomitant and adjuvant temozolomide treatment. Despite the use of this state-of-the-art treatment regimen, the median survival time of patients with glioblastoma is only 14.6 months.1 Well-established favorable prognostic factors include the addition of RT and novel chemotherapeutic agents such as temozolomide, the maximal extent of surgical resection, younger age, and a higher Karnofsky Performance Score 2-5 . The addition of RT to treatment protocols in three randomized phase III trials demonstrated an approximate doubling of survival and has been the considered standard of care since the late 1970's. [6][7][8] The standard time for RT for most patients is between two and six weeks following surgery 6,9-12 ; however, in certain resource-limited centers, it may be as long as ABSTRACT: Background: Radiation therapy (RT) is the major component of glioblastoma treatment; however, the time to initiate RT after surgical intervention varies between institutions. Our study examined the time from diagnosis to the initiation of RT and its effects on overall patient survival. Methods: We retrospectively examined 267 patients with glioblastoma who received RT as part of their therapy in two Canadian tertiary care centers. The primary goal of the study is to assess if time to RT can predict/impact survival in glioblastoma patients. Results: The following variables were associated with an increased risk of death: hazard ratio (HR) of time to RT was 0.95 [95% confidence interval (CI), 0.91-0.99] for every extra week. HRs for the type of surgery (resection or biopsy) and type of management received (standard of care in comparison with RT regardless of chemotherapeutic agents other than concomitant and adjuvant temozolomide) were 0.50 (95% CI, 0.37-0.66) and 0.53 (95% CI, 0.38-0.75), respectively. HR for age was 1.02 (95% CI, 1.01-1.03) for every extra year. Standard 60 Gy RT HR was 0.70 [95% confidence interval (CI), 0.51-0.97] in younger patients. Conclusions:The time from diagnosis to the initiation of RT was found to be a significant prognostic factor for overall patient survival. The addition of temozolomide to the treatment protocol, age, standard RT dose in younger patients and extent of surgery are others factors associated with longer survival periods.RÉSUMÉ: Impact potentiel de la radiothérapie différée chez les patients atteints d'un glioblastome. Contexte : la radiothérapie (RT) est l'élément le plus important du traitement du glioblastome. Cependant, le moment du début de la RT après la chirurgie varie selon les institutions. le but de l'étude était d'examiner le temps écoulé à partir du moment où le diagnostic a été posé jusqu'au moment où la RT a été commencée et ses effets sur la survie globale des patients. Méthode : Nous avons examiné rétrospective...

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Delay in radiotherapy shortens survival in patients with high grade glioma

Cited by 104 publications

References 11 publications

Survival impact of time to initiation of chemoradiotherapy after resection of newly diagnosed glioblastoma

Survival impact of time to initiation of chemoradiotherapy after resection of newly diagnosed glioblastoma

Brain tumors in Sweden: Data from a population-based registry 1999–2012

The Potential Impact of Delayed Radiation Therapy on Patients with Glioblastoma

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