Failure pattern following complete resection plus radiotherapy and temozolomide is at the resection margin in patients with glioblastoma

Abstract

Glioblastomas (GBM) are highly motile cancers that invade through normal brain. In the absence of curative chemotherapy this invasion, beyond surgical and radiotherapy margins, to distant brain sites is thought to be an important cause of treatment failure. Paradoxically, studies analyzing failure patterns have consistently shown that the large majority of failures occur at the original tumor site. This conflict may be explained by the fact these cancers are often only sub-totally resected and radiotherapy and chemotherapies fail to control this significant local cancer burden. We analyzed the failure pattern in 20 consecutive patients with complete resection of the gadolinium-enhancing portion of GBM demonstrated on the immediate post-operative magnetic resonance study, and who underwent a radical course of radiotherapy and chemotherapy. We found that recurrences occurred only at the resection margin in 17 of 20 patients. Recurrences were exclusively distant in 2 of 20 patients and occurred at both the resection margin and a distant site in 1 of 20 cases. We found that even in cases of complete resection of the gadolinium-enhancing portion of GBM 85 % of recurrences are localized to the resection margin.

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

“…Temozolomide, a DNA methylating agent, is the first-line drug used in concomitant and adjuvant radiochemotherapy against glioblastoma [32][33][34]. However, a large subset of patients is resistant to temozolomide due to the expression of the O 6 -methylguanine-DNA methyltransferase gene (MGMT), a DNA repair protein, and there is an urgent need for alternative mono-and combination therapies [35].…”

Stimulated Raman scattering microscopy for rapid brain tumor histology

“…Both beams are overlapped spatially and temporally, and interact with the samples through a laser scanning microscope. In most cases, the Stokes beam is modulated at radio frequencies (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) where the noise spectrum of the laser has reached a shotnoise°oor. After the sample, the pump beam is ltered out and sent to the photodiode (PD), and the SRL signal is demodulated by a lock-in amplier.…”

“…Hence, tumor is often left behind and more than 85% of glioblastoma (GBM) recurrences occur at the resection margins, resulting in treatment failure and poor outcome. 3,4 Conversely, unnecessary removal of normal brain tissues that do not contain cancer cells would generate neurological de¯cits. 5,6 Second, a precise assignment of the tumor type and grade is signi¯cant becausē rst-rank medical treatment varies widely depending on histological subtypes.…”

“…7 The importance of intraoperative histological classi¯cation during tumor surgery has been recognized for nearly 85 years. 3 Third, diverse neuropathologies such as demyelination, primary CNS lymphoma or radiation injury caused by treatment of radiotherapy to known tumors are di±cult to be distinguished from glioma by magnetic resonance imaging (MRI) or computed tomography (CT). 8,9 Thus, the risks of surgical resection are high for patients with aforementioned non-neoplastic conditions.…”

Clinical Applications of Synthetic MRI of the Brain

“…[65][66][67][68] There is also evidence that the resection of FLAIR or DTI abnormalities beyond the contrast-enhancing part of the tumour can have an impact on outcome in glioblastoma patients [69,70] and that tumours reoccur predominantly at the resection margin. [71] The peritumoral oedema is therefore an area which is being thoroughly investigated with different techniques for a better assessment of tumour infiltration, including, e.g., diffusion [64,72,73], perfusion [74], and relaxometry. [75] MR perfusion of the peritumoral area of malignant gliomas shows an increase in relative cerebral blood volume (rCBV) compared to metastases [76] due to the pathological neoangiogenesis induced by the glioma.…”