Predicting the biological characteristics of diseases through non-invasive means can be considered as the ultimate goal of radiology. Magnetic resonance imaging (MRI) can help characterize the tissues of interest from a variety of perspectives. Indeed, MRI is expected to provide profound information pertaining to glioblastoma beyond mere anatomical and geometrical extension of the disease within the brain. Recent advances in computational radiology and bioinformatics have facilitated the novel concept of “radiogenomics” in the field of radiology. This rapidly expanding research field entails construction of mathematical algorithms that help predict the genetic characteristic of neoplasms by combining hundreds or thousands of quantitatively evaluated radiographical textures. Radiogenomics involves four procedures, i.e., image normalization, lesion segmentation, texture extraction, and mathematical modeling. Each procedure requires profound knowledge of image analysis. However, the lack of a commercially-available analytic system is a barrier to the validation of observations from different research groups. Despite these constraints, it is still possible to identify the trend and the potential applications of radiogenomics in the context of glioma. For example, although prediction of IDH mutation in lower grade glioma seems to be feasible, prediction of MGMT promoter methylation status in newly diagnosed glioblastoma (nGBM) is a challenge. On the other hand, several reports have shown the promising potential of radiogenomics in prognostic assessment of nGBM. In this review article, the author aimed to address the basics as well as the most promising applications of radiogenomics in the context of nGBM while carefully respecting the limitations of this novel technique.
Glioblastomas are highly proliferative and invasive tumors ; therefore complete removal is typically not feasible. Several retrospective analyses suggest that maximal safe resection of glioblastoma may help improve the prognosis. Nevertheless, the indication for surgery should be carefully evaluated as improper patient selection for surgery may worsen the prognosis, especially for recurrent cases. Recent years have witnessed the development of several advanced surgery-related technologies such as tractography, intraoperative functional mapping, photodynamic diagnosis using 5-aminolevulinic acid, gliadel carmustine wafer treatment, and photodynamic therapy. Despite the advances in knowledge and technologies for surgical resection of glioblastoma, there are several unresolved issues ; these include the determination of the appropriate tumor resection boundary, the surgical indications for elderly patients with glioblastoma, lack of in-depth characterization of brain plasticity, development of surgical strategies based on molecular and genetic profile of tumor, and the establishment of modalities for immunotherapy. Resolution of these issues and further technological advances is expected to further improve the outcomes of glioblastoma surgery in the future.
The recent advances in next-generation sequencing have enabled the clinical application of cancer genome analysis in conjunction with artificial intelligence. In 2019, the cancer genome core base hospitals were established. In June 2019, two kinds of cancer-panels were covered by public insurance. Genome-based precision medicine has shown rapid advances and every core hospital makes every effort to catch up with the developments. However, there are still several constraints, such as the overall system, budget, and human resources.
While grappling with these issues, what can we do for patients with refractory brain tumors, including glioblastoma?
In this article, I would like to discuss the current status and the future perspectives of cancer genome precision medicine in the context of brain tumors.
In Japan, we can use radiation therapy (RT), temozolomide (TMZ), bevacizumab (BEV), and tumor treating electric fields via non-invasive, transducer arrays (TTFields). The standard adjuvant therapy for glioblastoma is local RT (60Gy) with concurrent TMZ, followed by maintenance treatment with TMZ, with optional addition of TTFields. The National Comprehensive Cancer Network guidelines recommend hypofractionated RT in elderly patients and patients with Karnofsky Performance Status＜60. TMZ monotherapy is another option for these patients if the MGMT-methylation status of tumor is proven. BEV helps improve brain edema but does not prolong the overall survival. Physicians need to be aware of the adverse effects of bevacizumab such as hypertension, proteinuria, and thromboembolic complications. The challenge is to identify the patients who can truly benefit from BEV. Discovery of new molecular targets and stratification of patients are key imperatives.
We are currently observing a plethora of new anti-cancer drugs which represent the fruits of extensive cancer research conducted over the past several decades. Some of these novel drugs can help achieve practical cure in hitherto deadly cancers. On the other hand, the prognosis of glioblastoma still remains one of the worst. This may be a good time to reflect on the reasons and the underlying mechanisms of such poor prognoses in glioblastomas. Some of the obvious reasons include the location, the highly invasive nature, and resistance to radiation, chemotherapy, and immunotherapy. Several novel therapeutic strategies are being developed to overcome these obstacles. Here we analytically summarize this topic.
We report an unusual case with de novo development of anterior condylar confluence dural arteriovenous fistula (ACC-DAVF) and transverse-sigmoid (TS) DAVF one year after endovascular treatment of cavernous sinus (CS) DAVF. A 74-year-old female was admitted to our hospital after presenting with headache. The diagnostic magnetic resonance imaging and digital subtraction angiography (DSA) revealed CS-DAVF (Borden type III). Transvenous embolization (TVE) for this lesion failed, but DSA at two weeks after the intervention showed disappearance of the CS-DAVF and occlusion of the ipsilateral sigmoid sinus. However, one-year follow-up DSA revealed de novo ipsilateral ACC-DAVF (Borden type I) and TS-DAVF (Borden type II). TVE and transarterial embolization (TAE) were successfully performed for the TS-DAVF. No recurrence was seen at the one-year follow-up.
After treatment of a DAVF, especially combined with iatrogenic occlusion of sigmoid sinus, de novo DAVFs may occur at other sites. Thus, careful radiological follow-up is recommended.