Correlation Of Magnetic Resonance Imaging With Individual Surgical Resection And Molecular Markers In Patients With Glioblastoma

Part Ⅰ:The analysis of prognostic factors for glioblastoma multiformeBackground and objective:Gliomas referred to as neurogliocytoma or gliocytoma are the most frequent tumors of the central neurvous system (CNS), which accounts for nearly half the number of intracranial primary tumors。These are classified based on the morphological criteria as astrocytomas,oligodendrogliomas, ependymomas。Different histologic subtypes of glioma show wide diversity with location, histopathologic features, genetic traits, molecular genetics status, clinical outcome。 World health organization (WHO) graded gliomas based on the histopathologic types as low-grade glioma (WHO Ⅰ-Ⅱ) and high-grade glioma (WHO Ⅲ-Ⅳ)。 Despite intensive therapies, including surgery, radiotherapy, and chemotherapy, prognosis of glioma patients remains depressing owing to tumor excessive invasive growth and restriction of brain anatomy。Different from the relatively favourable prognosis in low-grade glioma patients, the prognosis of high-grade gliomas patients is poor, usually patients with malignant glioma dying of progress of tumor 1 to 3 years after surgery, especially in patients with glioblastoma(GBM)。GBM is not only the most malignant astrocytoma (WHO IV), but is the most frequent glioma, which accounts for more than half the number of glioma。 To explore the effective treatment, Many neurooncologist have made great efforts。Although lacking of way to cure the disease up to now, as we know every failure and effort have laid the foundation of deeply understanding the mechanism of tumorigenesis。 The traditional neurosurgery rely too much on surgens’own experience and skills, casusing a high rate of postoperative complications and death。The application of modern comprehensive neuronavigation and intraoperative magnetic resonance imaging for minimally invasive brain tumour surgery to help design scalp incision, choose appropriate approach, help intraoperative localization of important brain structure, help judge extent of residual tumor is being widely used。The extent of residual tumor in operation is evaluated by neurosurgeon according to tumor color, texture, location。Fluorescent guided neurosurgery by way of tumor fluorescence under a microscope to guide and judge extent of resection becomes available. Era of radiotherapy from the initial administration of the whole brain radiotherapy, interstitial radiotherapy develops into the era of three-dimensional conformal intensity modulated radiation therapy。Era of chemotherapy from the initial administration of few chemotherapy drugs available develops into the era of Temozolomide with oral tolerance, higher blood brain transmittance and less adverse reactions。Additionally, with vigorous development of molecular biology, genetics and cell engineering, tumor immune therapy and gene therapy becomes the new field followed surgery, radiotherapy and chemotherapy treatment mode. Despite treatment appear as flowers, the prognosis of patients with glioblastoma is still very poor。According to the latest study from authority, although received the largest safe resection, postoperative use"stupp scheme"for concurrent chemoradiotherapy therapy as well as adjunct therapy with temozolomide, GBM patients’prognosis is still not ideal, which the median survival time is 16.8months。Factors influencing the prognosis of patients with glioblastoma multiforme are numerous, such as tumor biological behavior, molecular genetics feature, treatment scheme, the patients’wish to survival and financial status。Investigate the clinical factors influencing prognosis of patients with glioblastoma multiforme is of great significance to formulate individualized, standardized and effective treatment scheme。Methods and materialsBy checking the medical records of electronic medical record system from Nanfang Hospital, Southern Medical University,198 cases of clinical data of patients Jan 2008 to Jan 2013 are analyzed retrospectively, including gender, age, onset time, epilepsy before operation, preoperative Karnofsky performance status, tumor location, tumor size, cystic degeneration, extent of resection, postoperative Concurrent chemoradiotherapy, postoperative intracranial infection。Survival time in patients with primary GBM is acquired by telephone follow-up。Overall survival was defined as the time between the first surgery and death of progress of tumor。All of patients’families have signed informed consent。Statistical methodsAll statistical analyses were conducted with SPSS 17.0 for Windows。 Kaplan-Meier method was used to analyze the 11 possible factors which related to the prognosis, and then analyzed them with Cox multivariate regression analysis。The threshold for statistical significance was P=0.05。ResultsA total of 198 patients were enrolled,107 patients (54%) were male,91 patients (46%) were female; age range 16 to 76y; average (49.04±14.39y); 132 cases were located in noneloquent brain areas (prefrontal, temporal, parietal, occipital lobe and cerebellum),67 cases were located in eloquent brain areas (the brain stem, thalamus, pineal gland, language area, movement area) o Postoperative intracranial infection occurred in 11cases, accouting for 5.6 percent of all patients。 Following a univariate regression analysis, with no epilepsy before operation, good preoperative Karnofsky performance status, location of tumor, extent of resection, postoperative Concurrent chemoradiotherapy and postoperative intracranial infection associated with better overall survival rates(p<0.05). The prognosis of patients without epilepsy before operation is better than patients with epilepsy before operation (P=0.041); the prognosis of patients in noneloquent brain areas is better than patients in eloquent brain areas (P<0.001); the prognosis of patients with preoperative Karnofsky performance status>70 is better than patients with preoperative Karnofsky performance status< 70 (P<0.001); the prognosis of patients with radical surgery is better than patients with conservative surgery (P<0.001); the prognosis of patients with postoperative Concurrent chemoradiotherapy is better than patients without postoperative Concurrent chemoradiotherapy (P=0.002)。Multivariate Cox regression analysis found that Extent of resection (P<0.001), location of tumor (P=0.003), KPS (P=0.005), postoperative Concurrent chemoradiotherapy (P=0.016) and postoperative intracranial infection (P=0.046)were independent prognostic factors influencing the survival。Conclusion①Our results suggest that Extent of resection, location of tumor, postoperative KPS, Concurrent chemoradiotherapy were independent prognostic factors influencing the survival.② It is likely that the patients with intracranial infection postoperatively have more prolonged survival because infection can stimulate immune response to tumor.Part Ⅱ The relationship between MRI features and immunohistochemical expression of IDH1, MGMT in glioblastomaBackground and objective:Glioblastoma is the most malignant brain tumor and occurs in any age, more frequently in the elderly。 There is not clearly found boundary between tumor and normal brain tissue due to aggressive tumor growth of GBM。 Although received the largest safe resection, postoperative use"stupp scheme"for concurrent chemoradiotherapy therapy as well as adjunct therapy with temozolomide, GBM patients’median survival time is 14-15months, The estimated 5-year survival rate for patients with this disease remains<5%,but within this population there is pronounced heterogeneity of outcomes。 GBM is diagnosed based on the morphological criteria。 However, Clinical experiences derived from the prospective randomized clinical trials have shown that the histomorphological criteria alone might not be sufficient to predict the clinical outcome. Moreover, lately integrated genomic studies and exome sequencing have revealed the existence of multiple distinct molecular subtypes within histologically similar looking tumors。 Gliomas even with identical histopathological features different considerably regarding clinical course or response to therapy。 O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and mutations in isocitrate dehydrogenase (IDH) IDH1/2genes have been identified as potent prognostic factors in glioblastoma。By detecting the expression of genetic features helps neurosurgeons to master the biological characteristics of tumor, predict the long-term prognosis in patients, formulate appropriate therapy scheme。The relationship between expression of isocitrate dehydrogenase 1 (IDH1) mutations, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and magnetic resonance imaging (MRI) features in glioblastoma (GBM) is not clarified。It is necessary to evaluate the relationship between immunohistochemistry of isocitrate dehydrogenase 1 (IDHl),06-methylguanine-DNA methyltransferase (MGMT) and magnetic resonance imaging (MRI) features in supratentorial glioblastoma (GBM).Methods and materialsBy checking the medical records of electronic medical record system from Nanfang Hospital, Southern Medical University,111 patients with pathologically diagnosis of GBM retrospectively analized from Jan 2008 to Dec 2013 between immunohistochemistry of IDH1, MGMT and MRI features was summarized including gender, age, relapse, number of lesions, tumor location, maximum diameter of tumor, Magnetic Resonance Imaging sequence (T1WI,T2WI, MRI enhancement pattern, fluid attenuated inversion recovery sequence, diffusion weighted imaging), peritumoral edema, cystic degeneration, necrosis, hemorrhage。 Then, to evaluate the relationship between immunohistochemistry of isocitrate dehydrogenase 1 (IDH1), O6-methylguanine-DNA methyltransferase (MGMT) and above-mentioned factors。Statistical methodsAll statistical analyses were conducted with SPSS21.0 for Windows。 Kaplan-Meier method was used to analyze the 15 possible factors which related to immunohistochemically IDH1 positive and immunohistochemically MGMT positive,and then analyzed them with Logistic multiple regression analysis。 Using pearson’Chi Square test is to analyse ranked data and two independent sample t test is to analyse classified variables。The threshold for statistical significance was P=0.05o ResultsA total of 111 patients were enrolled,29 patients (26.1%) were immunohistochemically IDH1 positive,60 patients (26.1%) were immunohistochemically MGMT positive. The univariate analysis of IDH1 was associated with the maximum diameter of tumor (χ2=9.400, P=0.009), MRI enhancement pattern (t=2.204, P=0.030), peritumoral edema (PTE) (χ2=6.411, P=0.041) and main location (t=2.788, P=0.006). After the Logistic multiple regression, the maximum diameter of tumor (P=0.015), MRI enhancement pattern (P=0.037) and main location (P=0.024) were the significant predictors, and the maximum diameter of tumor was the most important factor (P<0.05). The univariate analysis of MGMT was associated with the quantity of tumor (χ2=6.678, P=0.010), diffusion weighted imaging (DWI) (t=-4.320,P=0.000), cystic (χ2=16.185, P=0.000), necrosis (χ2=8.325, P=0.004) and main location (t=2.612, P=0.010). After the Logistic multiple regression, quantity of tumor (P=0.008), cystic change (P=0.000) and DWI (P=0.000) were the significant predictors, and DWI is the most important predictor (P<0.05).ConclusionsThe immunohistochemistry of IDHland MGMT is relative to the MRI features. It is useful to preoperativly estimate the GBM’s biological behavior and prognosis by analysis of the relationship between the radiological and pathological features.