Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis

Biological effect of an alternating electric field on cell proliferation and synergistic antimitotic effect in combination with ionizing radiation

Glioblastoma, the most common primary brain tumor in adults, is an incurable malignancy with poor short-term survival and is typically treated with radiotherapy along with temozolomide. While the development of tumor-treating fields (TTFields), electric fields with alternating low and intermediate intensity has facilitated glioblastoma treatment, clinical outcomes of TTFields are reportedly inconsistent. However, combinatorial administration of chemotherapy with TTFields has proven effective for glioblastoma patients. Sorafenib, an anti-proliferative and apoptogenic agent, is used as first-line treatment for glioblastoma. This study aimed to investigate the effect of sorafenib on TTFields-induced anti-tumor and anti-angiogenesis responses in glioblastoma cells in vitro and in vivo. Sorafenib sensitized glioblastoma cells to TTFields, as evident from significantly decreased post-TTFields cell viability (p < 0.05), and combinatorial treatment with sorafenib and TTFields accelerated apoptosis via reactive oxygen species (ROS) generation, as evident from Poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore, use of sorafenib plus TTFields increased autophagy, as evident from LC3 upregulation and autophagic vacuole formation. Cell cycle markers accumulated, and cells underwent a G2/M arrest, with an increased G0/G1 cell ratio. In addition, the combinatorial treatment significantly inhibited tumor cell motility and invasiveness, and angiogenesis. Our results suggest that combination therapy with sorafenib and TTFields is slightly better than each individual therapy and could potentially be used to treat glioblastoma in clinic, which requires further studies.

The authors assessed the radiation-induced cancer risk due to organ doses from kilovoltage (kV) cone beam computed tomography (CBCT), a verification technique in image-guided radiotherapy (IGRT). CBCTs were performed for three different treatment sites: the head and neck, chest, and pelvis. Using a glass dosimeter, primary doses versus depth were measured inside a homemade phantom, and organ doses were measured at various locations inside an anthropomorphic phantom. The excess relative risk (ERR), excess absolute risk (EAR), and lifetime attributable risk (LAR) for cancer induction were estimated using the BEIR VII models based on dose measurement. The average primary (i.e., in-field) doses at the center of the phantom for standard imaging options were 1.9, 5.1, and 16.7 cGy for the head and neck, chest, and pelvis, respectively. The average secondary dose per scan for the pelvis measured 20–50 cm from the isocenter and ranged from 0.67–0.02 cGy, whereas the secondary dose per scan for the head and neck ranged from 0.07–0.003 cGy, indicating that CBCT for treatment of the head and neck is associated with a smaller secondary radiation dose than CBCT for treatment of the pelvis. The estimation of LAR from CBCT in IGRT indicated that the lifetime cancer risk for major organs can reach approximately 400 per 10,000 persons if 30 CBCT scans are performed to position a patient during radiation treatment of the pelvis site.

Background. This study was designed to compare the quality assurance (QA) results of four dosimetric tools used for intensity modulated radiation therapy (IMRT) and to suggest universal criteria for the passing rate in QA, irrespective of the dosimetric tool used. Materials and methods. Thirty fields of IMRT plans from five patients were selected, followed by irradiation onto radiochromic film, a diode array (Mapcheck), an ion chamber array (MatriXX) and an electronic portal imaging device (EPID) for patient-specific QA. The measured doses from the four dosimetric tools were compared with the dose calculated by the treatment planning system. The passing rates of the four dosimetric tools were calculated using the gamma index method, using as criteria a dose difference of 3% and a distance-to-agreement of 3 mm. Results. The QA results based on Mapcheck, MatriXX and EPID showed good agreement, with average passing rates of 99.61%, 99.04% and 99.29%, respectively. However, the average passing rate based on film measurement was significantly lower, 95.88%. The average uncertainty (1 standard deviation) of passing rates for 6 intensity modulated fields was around 0.31 for film measurement, larger than those of the other three dosimetric tools. Conclusions. QA results and consistencies depend on the choice of dosimetric tool. Universal passing rates should depend on the normalization or inter-comparisons of dosimetric tools if more than one dosimetric tool is used for patient specific QA.