Relapse patterns and radiation dose exposure in IDH wild-type glioblastoma at first radiographic recurrence following chemoradiation

Abstract

Purpose To quantify the radiation dose distribution and lesion morphometry (shape) at baseline, prior to chemoradiation, and at the time of radiographic recurrence in patients with glioblastoma (GBM). Methods The IMRT dose distribution, location of the center of mass, sphericity, and solidity of the contrast enhancing tumor at baseline and the time of tumor recurrence was quantified in 48 IDH wild-type GBM who underwent postoperative IMRT (2 Gy daily for total of 60 Gy) with concomitant and adjuvant temozolomide. Results Average radiation dose within enhancing tumor at baseline and recurrence was ≥ 60 Gy. Centroid location of the enhancing tumor shifted an average of 11.3 mm at the time of recurrence with respect to pre-IMRT location. A positive correlation was observed between change in centroid location and PFS in MGMT methylated patients (P = 0.0007) and Cox multivariate regression confirmed centroid distance from baseline was associated with PFS when accounting for clinical factors (P = 0.0189). Lesion solidity was higher at recurrence compared to baseline (P = 0.0118). Tumors that progressed > 12 weeks after IMRT were significantly more spherical (P = 0.0094). Conclusion Most GBMs recur local within therapeutic IMRT doses; however, tumors with longer PFS occurred further from the original tumor location and were more solid and/or nodular.

RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults

“…An exception is in the first 12 weeks after completion of radiochemotherapy in IDH wild-type glioblastoma, when pseudoprogression is most commonly observed. 28 In this period, if imaging studies show worsening, for clinically stable patients, a repeat MRI should be performed to confirm progression before taking a patient off study (Tables 1 and 3 and Data Supplement, Figs S3A and S3D). We recognize that there may be therapies that are especially likely to be associated with high rates of pseudoprogression or radiation necrosis (eg, intratumoral therapies such as oncolytic viruses).…”

“…Since the incidence of pseudoprogression is high in the first 12 weeks after chemoradiotherapy for glioblastomas (occurring in up to 30%-40% of patients), 9,25,28,29 and there is poor correlation between radiologic changes and PD and survival during this period, 9 we propose that if a patient with concern for radiologic progression during this period is clinically stable, a repeat MRI should be performed (eg, at 4-or 8-week intervals) to confirm progression (additional 25% or more increase in area or 40% increase or more in volume compared with previous scan) before necessitating a patient coming off study. If follow-up imaging supports true tumor progression, the date of progression should be backdated to the time of the scan when progression was first measured.…”

μMESH-Enabled Sustained Delivery of Molecular and Nanoformulated Drugs for Glioblastoma Treatment

“…4,5 Perhaps even more importantly, there is no standard of care in the event of a disease relapse, which occurs in ∼90% of the patients with the formation of secondary masses typically within 1 to 2 cm from the original tumor. 6 Such a dismal prognosis mainly draws from two unique features of GBM: anatomical barriers, whereby the access to the diseased tissue of blood-borne agents is tremendously impaired by the presence of the blood−brain barrier (BBB) and a thick hyaluronan-rich extracellular matrix (ECM), 7−9 and biological heterogeneity, resulting from the rapid and unbounded proliferation of malignant cells surrounded by a continuously morphing tumor microenviron- ment (TME) enriched by different subsets of immune and glioblastoma stem cells. 10−12 In this context, drug delivery systems for locoregional therapies are expected to have unique advantages over systemic approaches as they would bypass the BBB and fully exploit the fact that the brain is a "closed system" in which therapeutic agents could achieve long halflives.…”

“…Despite the drop in cancer death rates over the last three decades, which has been mostly dictated by pervasive prevention and screening campaigns as well as more effective targeted therapies, glioblastoma (GBM) continues to be the less curable form of cancer with a 5-year survival rate of only 5%. , The standard of care for GBM has not changed over the past 20 years, as it still relies on maximal safe resection of the malignant mass followed by adjuvant radiochemotherapy: the Stupp’s protocol . This complex and expensive treatment provides only a modest improvement in life expectancy and various degrees of therapy-induced complications, including the deterioration of physical, emotional, and social functions. , Perhaps even more importantly, there is no standard of care in the event of a disease relapse, which occurs in ∼90% of the patients with the formation of secondary masses typically within 1 to 2 cm from the original tumor . Such a dismal prognosis mainly draws from two unique features of GBM: anatomical barriers, whereby the access to the diseased tissue of blood-borne agents is tremendously impaired by the presence of the blood–brain barrier (BBB) and a thick hyaluronan-rich extracellular matrix (ECM), − and biological heterogeneity, resulting from the rapid and unbounded proliferation of malignant cells surrounded by a continuously morphing tumor microenvironment (TME) enriched by different subsets of immune and glioblastoma stem cells. − In this context, drug delivery systems for locoregional therapies are expected to have unique advantages over systemic approaches as they would bypass the BBB and fully exploit the fact that the brain is a “closed system” in which therapeutic agents could achieve long half-lives.…”