Early initiation of chemoradiation following index craniotomy is associated with decreased survival in high-grade glioma

Abstract

The Stupp protocol of post-resection external beam radiation therapy and concomitant temozolomide is the standard of care for patients with newly-diagnosed glioblastoma, with expanded use in anaplastic astrocytoma. However, the optimal interval between surgery and these adjuvant therapies, and its impact on survival, is unknown. To investigate this, de-identified claims from a large, private health insurance database were queried to identify adult patients who underwent index craniotomy for resection of a supratentorial neoplasm during the period 2005-2014 and began postoperative radiation and temozolomide within 13 weeks of surgery. A total of 2535 patients were assigned to groups based on interval from surgery to first radiation treatment of up to 4 weeks, 4-6 weeks, or 6-13 weeks. Of these, 1098 patients began radiation treatment within 4 weeks of craniotomy, 1019 between 4 and 6 weeks, and 418 between 6 and 13 weeks. There was significant regional variation in treatment schedule in the United States. Survival was calculated based on time from first craniotomy to death. Kaplan-Meier plot and multivariate Cox proportional hazard regression demonstrated a statistically significant association between earliest postoperative radiation and decreased survival (hazard ratio 1.31), along with older age and male sex. Earlier initiation of postoperative radiation for high-grade glioma is not associated with increased survival. Rather, beginning radiation treatment within 4 weeks of craniotomy was associated with significantly worse survival compared to initiation of treatment 4-13 weeks after craniotomy. This is the largest population-based study to date regarding timing of Stupp protocol initiation.

The relationship between the waiting time of postoperative radiotherapy and the prognosis of high grade glioma:a systemic review and meta-analysis

“…The most representative article published by Nathan [27] ,which included 2,535 patients with high-grade glioma and was divided into three groups according to different time intervals (0-28d, 28-42d, 42-91d).It was found that patients who started radiotherapy at 42d after surgery had a better prognosis than those who started radiotherapy within 28d after surgery.Kaidar-person [33] also found that patients lived longer who started radiotherapy more than 42d.These results are conflicted with the conclusions from the early comprehensive analysis by Lauwrence (that the prognosis of patients is poor while radiotherapy delayed over 6 weeks) .However, no radiobiological results have been reported to explain this phenomenon.…”

Bevacizumab Use and the Risk of Arterial and Venous Thromboembolism in Patients with High‐Grade Gliomas: A Nested Case‐Control Study

“…We selected a retrospective cohort of patients receiving treatment for high‐grade gliomas under the Stupp protocol using a validated algorithm for administrative claims databases . To be eligible for study inclusion, patients were required to have undergone incident craniotomy on or after January 1, 2010; had initiated radiation therapy within 91 days of surgical resection; had initiated temozolomide within 91 days of craniotomy; and had continuous enrollment during the 1 year before craniotomy.…”

“…Patients with glioblastoma have a 5‐year survival rate ranging between 0.5% and 4.7% in the United States . Standard care for incident (first‐time) high‐grade glioma includes maximal surgical resection followed by radiotherapy and concurrent/adjuvant temozolomide, a treatment regimen referred to here as the Stupp protocol . Nearly all glioblastoma cases recur even in instances of apparent complete removal of the tumor .…”

The Value of Prognostic Factors for Glioblastoma Treated With Concurrent Thermochemoradiotherapy

“…В исследовании, включившем 4 584 пациентов с глиобластомой, было обнаружено, что увеличение времени начала лучевой терапии до 4-6 нед после операции является безопасным и может быть умеренно выгодным [25]. При этом начало адъювантного лечения в течение 3-4 нед после операции может иметь отрицательное прогностическое значение [26]. Результаты, полученные в нашем исследовании, показали, что безрецидивная выживаемость значи-clinical studies мо выше у пациентов, которым курс ТХЛТ начат через 6 и более недель после оперативного вмешательства.…”

“…Результаты, полученные в нашем исследовании, показали, что безрецидивная выживаемость значи-clinical studies мо выше у пациентов, которым курс ТХЛТ начат через 6 и более недель после оперативного вмешательства. Полученные результаты соответствуют литературным данным и могут быть обусловлены как отбором пациентов с меньшей скоростью прогрессирования опухоли, так и уменьшением послеоперационной гипоксии в перифокальной области в указанные сроки [25,26].…”