Outcomes of 30 Gy/5 Fr Hypofractionated Stereotactic Radiation Therapy for Small Brain Metastases (≤2 cm).

BACKGROUND/AIM: Stereotactic radiosurgery (SRS)-used for brain metastases (BMs) with a tumor diameter of ≤2 cm-has a high local control rate, however, it can cause symptomatic radiation-induced brain necrosis. Hypofractionated stereotactic radiation therapy (HFSRT) is not commonly used for such lesions and its effectiveness remains unknown. Herein, the efficacy of 30 Gy 5-fraction HFSRT for treating BMs of <2 cm was retrospectively evaluated. PATIENTS AND METHODS: Patients who received HFSRT and had a gross tumor volume (GTV) of ≤2 cm in maximum diameter were included in the study (49 patients; 179 BMs; median follow-up period, 11.9 months). RESULTS: The mean GTV Peripheral Dose (D95) was 36.2 Gy. The local control (LC) rates at 1 and 2 years were 93.0% and 81.5%, respectively, for all lesions. The 1-year LC rates were 93.6% and 92.0% for ≤1.0-cm and 1.0-2.0-cm lesions, respectively. Multivariate analysis revealed that the only significant difference was in GTV maximal tumor diameter (HR=1.961, p=0.0002). Notably, only one patient had asymptomatic radiation necrosis. CONCLUSION: Owing to the high toxicity of SRS, 5-fraction HFSRT can be an effective treatment strategy for BMs of <2 cm.

First Clinical Experience of Tungsten Rubber Electron Adaptive Therapy With Real-time Variable-shape Tungsten Rubber.

BACKGROUND/AIM: We investigated the dosimetric characteristics of electron radiotherapy for auricular keloid using real-time variable-shape tungsten rubber (STR). PATIENTS AND METHODS: For the first evaluation, STR was shaped into a rectangular irradiation field (3.0×5.0 cm2). In the next step, the STR was reshaped to fit the target (3.5×6.5 cm2) for the second evaluation. Percentage depth doses (PDDs) and lateral dose profiles were obtained with 6-MeV electron beams and compared with those of low-melting-point lead (LML). RESULTS: Compared to the LML on electron applicator, PDD differences were within 0.4 mm, while the penumbras as width of 20-80% dose levels were smaller (maximum reductions: 75.8% and 82.9% at first and second evaluations, respectively). The treatment process of shaping the STR, decision on output, and irradiation was completed within 45 min. CONCLUSION: Electron radiotherapy using STR for keloid can be performed with excellent dose distribution in a short time. First clinical experience found the STR is suitable for use in individualized and immediate electron radiotherapy.

Radiation dose reduction to the eye lens in head CT using tungsten functional paper and organ-based tube current modulation.

PURPOSE: We investigated whether a tungsten functional paper (TFP) shield and/or organ-based tube current modulation (TCM) can reduce the dose to the eye lens. MATERIALS AND METHODS: All scans were performed using our routine head examination protocol (spiral acquisition, 120 kVp, noise Index 3.5) with an anthropomorphic head phantom. The dose reduction rate was measured by the following methods with a scintillation fiber optic dosimeter: (a) without any dose reduction techniques (Original scan), (b) TFP shield, (c) TCM, and (d) TFP shield plus TCM. Image noise and CT number were obtained and compared between the three groups. In addition, image noise in method (d) was measured with varying distances between the TFP shield and eye lens. RESULTS: The reduction rates using TFP shield, TCM, and TFP shield plus TCM compared with those for the Original scan were 17.8 %, 13.6 %, and 27.7 %, respectively. Image noise (mean ± standard deviation) in the anterior region for the Original scan, TFP shield, TCM, and TFP shield plus TCM were 4.1 ± 0.2, 4.6 ± 0.2, 4.4 ± 0.3, and 5.0 ± 0.2, while the CT numbers were 19.3 ± 0.8, 23.8 ± 0.8, 19.6 ± 0.8, and 24.1 ± 0.8, respectively. Increasing the distance between the TFP and the eye significantly decreased the CT number when using TFP shield plus TCM (p < .05). CONCLUSION: TFP shield plus TCM reduced the dose to the eye lens in head CT while maintaining image quality with an air gap between the TFP and skin surface.

Dosimetric Characterization of a Novel Surface Collimator With Tungsten Functional Paper for Electron Therapy.

BACKGROUND/AIM: The aim of the study was to investigate the dosimetric characteristics of electron beams with a tungsten functional paper (TFP) surface collimator. MATERIALS AND METHODS: The circular field of 6.0 cm diameter was created with the TFP collimator put on the phantom. Depth and lateral dose profiles for 4 and 6 MeV electron beams were obtained. The characteristics of lateral dose profile, treatment diameter as width over 90% of the dose, and penumbra as width of the off-axis positions from 80% to 20% dose levels were evaluated. RESULTS: Compared to the lead collimator, the TFP collimator generated higher surface doses, the treatment diameters were increased from 42.8 to 48.6 mm and from 40.0 to 41.4 mm, and the penumbras were reduced from 15.0 to 9.6 mm and from 16.4 to 13.0 mm for 4 and 6 MeV electron beams, respectively. CONCLUSION: The TFP surface collimator can provide an excellent dose distribution compared to the conventional lead collimator.

Antiangiogenesis therapy using a novel angiogenesis inhibitor, anginex, following radiation causes tumor growth delay.

BACKGROUND: The present study investigated whether treatment with anginex, a novel antiangiogenic peptide, could block re-vascularization after radiation treatment. METHODS: A squamous cell (SCCVII) xenograft tumor mouse model was employed to assess the effects of anginex given post-radiation on tumor growth, microvessel density (MVD), and oxygen levels. The oxygen status was determined by the partial pressure of O2. RESULTS: Tumors in untreated mice increased threefold in 7.0 days, anginex-treated tumors (10 mg/kg intraperitoneal, twice) required 7.3 +/- 0.9 days, and tumors exposed to 8-Gy radiation increased threefold over 11 days. Combination treatment of anginex and radiation caused the tumors to grow threefold in 16.1 +/- 1.6 days, a delay which was significant and deemed supra-additive. Oxygen levels in tumors treated by stand-alone or combination therapies were significantly reduced; for example from 19.5 +/- 4.9 mmHg in controls to 9.7 +/- 1.9 mmHg in combination-treated, size-matched tumors. In addition, immunohistochemistry showed a decrease in MVD in the tumors treated with anginex, radiation, or the combination. These results suggest that a combination of anginex and radiation can greatly affect the amount of functional vasculature in tumors and prolong radiation-induced tumor regression. CONCLUSION: Antiangiogenesis therapy with anginex, in addition to radiotherapy, will be useful by blocking angiogenesis-dependent regrowth of vessels.

Synergistic effects of radiation and beta-lapachone in DU-145 human prostate cancer cells in vitro.

It has been reported that beta-lapachone (beta-lap), a bioreductive anti-cancer drug, synergistically interacts with ionizing radiation and that the sensitivity of cells to beta-lap is closely related to the activity of NAD(P)H:quinone oxidoreductase 1 (NQO1). Here we report the results of our studies of mechanisms underlying the synergistic interaction of beta-lap and radiation in killing cancer cells using the DU-145 human prostate cancer cell line. The clonogenic cell death caused by the combination of radiation and beta-lap was synergistic when beta-lap was administered 0-10 h after irradiation but not when it was given before irradiation. The expression and activity of NQO1 increased significantly and remained elevated for longer than 12 h after 4 Gy irradiation, suggesting that the long-lasting elevation of NQO1 sensitized the cells to beta-lap. Studies with split-dose irradiation demonstrated that beta-lap given immediately after irradiation effectively inhibited sublethal radiation damage (SLD) repair. Taken together, these results lead us to conclude that the synergistic interaction between beta-lap and radiation in killing cells is the result of two distinct mechanisms: First, radiation sensitizes cells to beta-lap by up-regulating NQO1, and second, beta-lap sensitizes cells to radiation by inhibiting SLD repair. The combination of beta-lap and radiotherapy is potentially promising modality for the treatment of cancer in humans.

Increase in tumor oxygenation and potentiation of radiation effects using pentoxifylline, vinpocetine and ticlopidine hydrochloride.

The purpose of the present study was to investigate the effects of Pentoxifylline (PTX), Vinpocetine (VPT) and Ticlopidine Hydrochloride (TCD), used commonly for vascular disorders in humans, on the pO2 in SCCVII tumors of C3H/HeJ mice and on the radioresponse of SCCVII tumors. The pO2 in the SCCVII tumors, which were measured 30 min after intraperitoneal (i.p.) injection of PTX (5 mg/kg), VPT (5 mg/kg), or TCD (10 mg/kg) using polarography, was compared to that in saline-treated control tumors. All the three drugs, PTX, VPT and TCD, yielded significant increase of the pO2 in the SCCVII tumors from 25.6 to 26.9 mmHg, from 18.6 to 22.9 mmHg, and from 22.6 to 25.9 mmHg, respectively. Frequency histogram of the pO2 distribution in the saline-treated SCCVII tumors did not show hypoxic fraction of less than 10 mmHg. The radioresponses of the drugs were investigated by tumor growth delay assay. In the drug-treated groups, the SCCVII tumors were irradiated with a single dose of 15 Gy 30 min after injection of the drugs at the same doses as those used in the experiments for intratumoral pO2 measurement. Compared with the irradiation alone group, significant tumor growth delays were observed in all the drug-treated groups. The time required to reach a four-fold increase in the initial tumor volume were 4 days in the saline-treated control group, 22 days in the irradiation (IR) alone group, 28 days in the PTX + IR group, 29 days in the VPT + IR group, and 32 days in TCD + IR group. In conclusion, VPT and TCD are potentially promising drugs for increasing the intratumoral pO2 although the mechanism for radiopotentiation observed in the present study is unknown due to small hypoxic fraction in the SCCVII tumors. Further studies on other mechanisms for radiopotentiation of PTX, VPT or TCD, besides of increasing the pO2 in the tumor, are needed.

Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor.

PURPOSE: Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy. MATERIALS AND METHODS: We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging(MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H&E) staining. RESULTS: Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an i.p. injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days. CONCLUSION: The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor.