Medical Oncology

To assess the role of comorbidity on outcome in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant Temozolomide, patients over 65 years with glioblastoma, who underwent surgical resection or biopsy and radiochemotherapy, were evaluated. The Adjusted-Age Charlson Comorbidity Index and the Adult Comorbidity Evaluation-27 were used to assess comorbidity. From April 2005 to January 2011, 35 patients (median age 72 years) were treated in our Institution. Thirteen patients had a Charlson score more than 3, while, according to the Adult Comorbidity Evaluation-27, 21 patients had mild or severe comorbid conditions. Patients with low Charlson comorbidity score experienced a longer survival time than those with higher score (22 vs. 10 months, respectively). The Adjusted-Age Charlson Comorbidity Index influenced survival at univariate and multivariate analysis (p = 0.004, p = 0.001, respectively). No comorbidity index was a predictor for progression-free survival. Our data suggested that the association of radiotherapy with TMZ was safe and effective. Perhaps, the comorbidity assessment could be an appropriate tool in the treatment decision for elderly patients with glioblastoma.

Delta-like ligand 4 (DLL4) is a ligand of the notch pathway. In tumor angiogenesis, DLL4 switches to vascular maturation by providing a negative feedback on VEGFR2 activity. We investigated the expression of DLL4 in the plasma and cancer tissues from breast cancer patients. Plasma samples were collected from 18 women with localized breast cancer, six women with benign breast disease and from six patients with widespread metastatic disease. DLL4 was assessed using ELISA and in cancer tissues using immunohistochemistry. Patients with metastatic breast cancer had significantly higher levels (median 6.7 ± 0.81 ng/ml) compared to patients with localized tumors (median 5.4 ± 0.70 ng/ml) (p = 0.005) and to patients with benign breast disease (median 4.3 ± 0.28) (p = 0.0003). High histology grade was significantly linked with higher plasma DLL4 levels (median 5.59 ± 0.62 vs. 5.12 ± 0.44 ng/ml; p = 0.01). Surgical removal of high-grade breast cancer resulted in significant reduction in DLL4 plasma levels (p = 0.003). DLL4 was expressed in tumor-associated vessels and in cancer cells. The ratio of DLL4+/CD31+ vascular density (VD) ranged from 23 to 88 % (median 49 %). High DLL4 cancer cell expression and high DLL4+ VD were significantly linked with nodal involvement (p = 0.004 and 0.01, respectively). Linear regression analysis showed a significant association of DLL4 plasma levels with the percentage of DLL4+ cancer cells (p = 0.03, r = 0.50) and with DLL4+ VD (p = 0.0007, r = 0.60). It is concluded that DLL4 is overexpressed in breast cancer cells and breast cancer vasculature and is linked with nodal and distant metastasis. DLL4 plasma levels measurement can reliably estimate the total DLL4 breast cancer/vasculature activity.

Novel treatment strategies such as gene therapy are warranted in view of the failure of current treatment approaches to cure a high percentage of patients with advanced bladder cancers. The emergence of cancer gene therapy potentially offers a number of exciting treatments. The majority of approaches involve strategies to suppress the function of activated oncogenes to restore the expression of functional tumour suppressor genes or to initiate tumour self-destruction. One gene therapy approach against tumours that holds great promise is suicide gene therapy. Herpes simplex virus thymidine kinase (HSV-TK) phosphorylates ganciclovir (GCV), which in turn interacts with cellular DNA polymerase and interferes with DNA synthesis to cause death of rapidly dividing cells. The development of an effective delivery system is absolutely critical to the usefulness and safety of gene therapy. At present, the adeno-associated virus (AAV) vector has the most promising potential in view of its non-pathogenicity, wide tropisms and long-term transgene expression in vivo. Gene therapy studies using different serotypes of recombinant AAV (rAAV) as delivery vehicles have proved rAAVs to be an effective modality of cancer gene therapy. In the present study, we investigated the suppression effect of AAV-mediated HSV-TK/GCV system on the bladder cancer cells and in mice xenograft models of bladder cancer. Our data demonstrate that rAAV-HSV-TK system controlled tumour cell growth and achieves strong antitumour efficacy in vivo. These findings provide a foundation for the development of potential targeted clinical therapies for bladder cancer in humans.

To investigate the differences in gene expression level between metastatic and non-metastatic osteosarcoma (OS) samples and the potential mechanism. Gene expression profile data GSE9508 were downloaded from Gene Expression Omnibus database to identify the differentially expressed genes (DEGs) between metastatic, non-metastatic OS samples, and normal control samples via SAM method. Function expression matrix of the DEGs was constructed by calculating the functional node scores based on the genes sets collected from the pathways recorded in MsigDB database. Next, t test was applied to screen the differentially expressed functional nodes between each two kinds of samples. Finally, we compared the significant genes between selected DEGs and genes in differentially expressed functional nodes. There were 79 up-regulated DEGs between non-metastatic OS and normal samples, 380 up-regulated and 134 down-regulated DEGs between the metastatic OS and normal samples, and 761 up-regulated plus 186 down-regulated DEGs between metastatic and non-metastatic OS samples. A total of 3846 functional gene sets were collected to form the function expression profile matrix. The numbers of differentially expressed functional nodes between non-metastatic OS and normal samples, metastatic OS and normal samples, and metastatic and non-metastatic OS samples were 8, 39, and 5, respectively. The gene level difference between metastatic and non-metastatic OS samples can be distinguished using bioinformatics analysis. TGFB1, LFT3, KDM1A, and KRAS genes have the potential to be used as biomarkers for OS; however, further analysis is needed to verify the current results.

The purpose of thermal ablation is induction of tumor death by means of localized hyperthermia resulting in irreversible cellular damage. Ablative therapies are well-recognized treatment modalities for HCC lesions and are considered standard of care for HCC nodules < 3 cm in diameter in patients not suitable for surgery. Effective lesion treatment rely on complete target volume ablation. Technical limitations are represented by large (> 3 cm) or multicentric nodules as well as complex nodule location and poor lesion conspicuity. Artificial Intelligence (AI) is a general term referred to computational algorithms that can analyze data and perform complex tasks otherwise prerogative of Human Intelligence. AI has a variety of application in percutaneous ablation procedures such as Navigational software, Fusion Imaging, and robot-assisted ablation tools. Those instruments represent relative innovations in the field of Interventional Oncology and promising strategies to overcome actual limitations of ablative therapy in order to increase feasibility and technical results. This work aims to review the principal application of Artificial Intelligence in the percutaneous ablation of primary lesions of the liver with special focus on how AI can impact in the treatment of HCC especially on potential advantages on the drawbacks of the conventional technique.

Hepatocellular carcinoma (HCC) is a malignant tumor driven by complex pathological mechanisms and is characterized by fast progression and poor prognosis. The main cause of death in HCC patients is tumor metastasis. However, underlying molecular mechanisms of metastasis are largely unknown in HCC. In the present study, a novel metastasis-related gene, leucine-rich-alpha-2-glycoprotein 1 (LRG1), was identified in HCC. We revealed that LRG1 expression was downregulated in HCC tissues by quantitative real-time PCR and immunohistochemical staining. In vitro assays demonstrated LRG1 had no effect on cell proliferation. Migratory and invasive potential of HCC cells was reduced by ectopic overexpression of LRG1, whereas silencing LRG1 could enhance migration and invasion of HCC cells. Furthermore, exogenous recombinant human protein of LRG1 could inhibit migration and invasion of HCC cells in vitro. The above findings indicate that LGR1 is involved in the inhibition of HCC metastasis and it may function as a novel metastasis suppressor in HCC.

To evaluate feasibility, safety, toxicity profile and dosimetric results of volumetric modulated arc therapy (VMAT) to deliver regional nodal irradiation (RNI) after either mastectomy or breast conservation (BCS) in high-risk breast cancer patients. Between January 2015 and January 2017, a total of 45 patients were treated with VMAT to deliver RNI together with whole breast or post-mastectomy radiotherapy. The fractionation schedule comprised 50 Gy in 25 fractions given to supraclavicular and axillary apex nodes and to whole breast (after BCS) or chest wall (after mastectomy). Two opposite 50°–60° width arcs were employed for breast ad chest wall irradiation, while a single VMAT arc was used for nodal treatment. Treatment was generally well tolerated. Acute skin toxicity was G2 in 13.3% of patients. Late skin toxicity consisted of G1 induration/fibrosis in six patients (13.3%) and G2 in 1 (2.2%). Dosimetric results were consistent in terms of both target coverage and normal tissue sparing. In conclusion, VMAT proved to be a feasible, safe and effective strategy to deliver RNI in breast cancer patients after either BCS or mastectomy with promising dosimetric results and a mild toxicity profile.