The Potential Impact of Delayed Radiation Therapy on Patients with Glioblastoma

Abstract

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...

Impact of time to initiation of radiotherapy on survival after resection of newly diagnosed glioblastoma

“…Since several studies suggested that there is a possible impact on survival when starting RT prematurely or with a significant delay, and although not our primary analysis goal due to important biases, we also conducted a survival analysis for the small subsets of patients that received RT earlier than 14 days or after 48 days postoperatively [14, 16, 22, 35, 41, 42]. A significantly shorter OS was shown for the patients that started RT after a prolonged delay.…”

Survival Impact of Delaying Postoperative Radiotherapy in Patients with Esophageal Cancer

“…Do et al [18] used multivariate analysis to assess the effect of radiotherapy delay on survival in a retrospective study of 182 patients with high-grade glioma and found no significant effect of delaying postoperative RT on OS. However, some other retrospective analyses found a significant unfavorable effect of shorter delays on OS [19] , [20] , [21] . Wurschmidt et al [22] assessed the importance of time interval between surgery and postoperative RT in non–small-cell lung carcinoma; controlling the status of resection margins and performance status, they found that the 175 patients who were irradiated at <36 days after surgery had a significantly detrimental survival compared with the 165 patients irradiated at ≥36 days after surgery.…”

The Role of Delayed Radiotherapy Initiation in Patients with Newly Diagnosed Glioblastoma with Residual Tumor Mass

“…17,18 Several observational studies with up to 2,388 patients published beneficial effects for either early initiation of irradiation after surgery [19][20][21] or postponed adjuvant therapy. [22][23][24][25][26] Possible explanations for the necessity of either early or late adjuvant irradiation were discussed before. This includes early radio-insensitivity due to postoperative hypoxia, 22 higher brain tissue damage in early irradiation, 27 or increased side effects by larger radiation fields due to an uncollapsed resection cavity.…”