BackgroundThe purpose of this study was to compare carbon ion radiotherapy (C-ion RT) and stereotactic radiotherapy (SBRT) with photon beams for the treatment of hepatocellular carcinoma (HCC), specifically with regard to the dose volume parameters for target coverage and normal tissue sparing.MethodsData of 10 patients who were treated using C-ion RT with a total dose of 60 Gy(RBE) in four fractions were used. The virtual plan of SBRT was simulated on the treatment planning computed tomography images of C-ion RT. Dose volume parameters such as minimum dose covering 90 % of the planning target volume (PTV D90), homogeneity index (HI), conformity index (CI), mean liver dose (MLD), volume of the liver receiving 5 to 60 Gy (V5-60), and max point dose (Dmax) of gastrointestinal (GI) tract were calculated from both treatment plans.ResultsThe PTV D90 was 59.6 ± 0.2 Gy(RBE) in C-ion RT, as compared to 56.6 ± 0.3 Gy in SBRT (p < 0.05). HI and CI were 1.19 ± 0.03 and 0.79 ± 0.06, respectively in C-ion RT, as compared to 1.21 ± 0.01 and 0.37 ± 0.02, respectively in SBRT. Only CI showed a significant difference between two modalities. Mean liver dose was 8.1 ± 1.4 Gy(RBE) in C-ion RT, as compared to 16.1 ± 2.5 Gy in SBRT (p < 0.05). V5 to V50 of liver were higher in SBRT than C-ion RT and significant differences were observed for V5, V10 and V20. Dmax of the GI tract was higher in SBRT than C-ion RT, but did not show a significantly difference.ConclusionsC-ion RT provides an advantage in both target conformity and normal liver sparing compared with SBRT.

Survivin is a member of the inhibitor of apoptosis family, and is expressed in various malignant tumors. Survivin overexpression has been reported to be a poorer prognostic factor in various malignancies. However, the prognostic value of survivin expression in patients with glioblastoma is still controversial. Therefore, in this study the role of survivin as a predictor for survival was investigated in patients with glioblastoma. Tissue specimens were obtained from 66 patients with glioblastoma treated with radiotherapy. Survivin expression was detected by an immunohistochemical method. Nuclear and cytoplasm survivin scores were defined by using the cell positivity and staining intensity. The scores were defined as follows, 0 (no staining), 1 (less than 50% of cell positivity and any staining), 2 (more than 50% of cell positivity and weak to moderate intensity) and 3 (more than 50% of cell positivity and strong intensity). The correlation between survivin scores and the overall survival rate was evaluated. Nuclear and cytoplasm survivin staining were noted in 47 and 58 patients, respectively. The number of patients with nuclear survivin score of 0, 1, 2 and 3, were 19 (28.8%), 26 (39.4%), 9 (13.6%) and 12 (18.2%), respectively. The 3-year overall survival rate of the nuclear survivin score 3 was 0%, significantly lower than the 11.6% of the nuclear survivin score

phosphorylated-Akt (pAkt) plays an important role in tumorigenesis through promotion of cell survival by inhibiting apoptosis and mediating cell proliferation. Higher expression of pAkt has been reported to be associated with an unfavorable prognosis in several malignant tumors. In this study, the prognostic value of pAkt expression was investigated in glioblastomas by using immunohistochemical methods. Tissue sections obtained from 64 patients with glioblastoma were evaluated. The mean and median follow-up period was 16.2 +/- 12.4 and 12 months, respectively (range: from 1 to 62 months). pAkt expression levels were determined by immunohistochemical staining and evaluated for cell positivity. Positive staining was defined when more than 50% of the tumor cells were stained in each section. The correlation between expression of pAkt and overall survival rate was assessed. Glioblastomas showed either or both cytoplasmic and nuclear positive findings for pAkt. A total of 29.7% (19/64) of tissue specimens had greater than 50% positivity. The median survival periods of the patients with pAkt positive and negative tumor were 10 and 14 months, respectively. Two years overall survival rate of the pAkt positive and negative patients were 0% and 24.4%, respectively. Survival rate of the patients with pAkt positive tumor was significantly lower than that of the patients with pAkt negative tumors (p = 0.004). Multivariate analysis showed that extent of surgery was the strongest factor for survival (p = 0.01) and the pAkt expression was the secondly strongest factor (p = 0.06). These results suggest that the higher expression of pAkt the poorer prognosis in patients with glioblastoma.

Conventional treatment of glioblastoma has advanced only incrementally in the last 30 years and still yields poor outcomes. The current strategy of surgery, radiation, and chemotherapy has increased median survival to approximately 15 months. With the advent of molecular biology and consequent improved understanding of basic tumor biology, targeted therapies have become cornerstones for cancer treatment. Many pathways (RTKs, PI3K/AKT/mTOR, angiogenesis, etc.) have been identified in GBM as playing major roles in tumorigenesis, treatment resistance, or natural history of disease. Despite the growing understanding of the complex networks regulating GBM tumors, many targeted therapies have fallen short of expectations. In this paper, we will discuss novel therapies and the successes and failures that have occurred. One clear message is that monotherapies yield minor results, likely due to functionally redundant pathways. A better understanding of underlying tumor biology may yield insights into optimal targeting strategies which could improve the overall therapeutic ratio of conventional treatments.