EP-1263: Survival and symptom relief after palliative radiotherapy for esophageal cancer

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Impact of treatment planning target volumen (PTV) size on radiation induced diarrhoea following selenium supplementation in gynecologic radiation oncology - a subgroup analysis of a multicenter, phase III trial

Background: In a previous analysis (Int J Radiat Oncol Biol Phys 70:828-835,2010), we assessed whether an adjuvant supplementation with selenium (Se) improves Se status and reduces the radiation-induced side-effects of patients treated by adjuvant radiotherapy (RT) for cervical and uterine cancer. Now, a potential relation between the planning target volume (PTV) of the RT and the Se effect concerning radiation induced diarrhoea was evaluated in detail. Methods: Whole blood Se concentrations had been measured in patients with cervical (n=11) and uterine cancer (n=70) after surgical treatment, during, and at the end of RT. Patients with initial Se concentrations of less than 84 μg/l were categorized as Se-deficient and randomized before RT to receive Se (as sodium selenite) per os on the days of RT, or to receive no supplement during RT. Diarrhoea was graded according to the Common Toxicity Criteria system (CTC, Version 2a). The evaluation of the PTV of the RT was ascertained with the help of a specialised computer-assisted treatment planning software used for radiation planning procedure. Results: A total of 81 patients had been randomized for the initial supplementation study, 39 of which received Se [selenium group, SeG] and 42 serving as controls [control group, CG]. Mean Se levels did not differ between SeG and CG upon study initiation, but were significantly higher in the SeG compared to the CG at the end of RT. The actuarial incidence of at least CTC 2 radiation induced diarrhoea in the SeG was 20.5% compared to 44.5% in the CG (p=0.04). The median PTV in both groups was 1302 ml (916–4608). With a PTV of 1302 ml (n=40) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 19.1% (4 of 21 patients) versus 52.6% (10 of 19 patients) in the CG (p=0.046). Conclusions: Se supplementation during RT was effective to improve blood Se status in Se-deficient cervical and uterine cancer patients, and reduces episodes and severity of RT-induced diarrhoea. This effect was most pronounced and significant in patients with large PTV (> 1302 ml)

Micronutrients in Oncological Intervention

Nutritional supplements are widely used among patients with cancer who perceive them to be anticancer and antitoxicity agents. Depending on the type of malignancy and the gender 30%–90% of the cancer patients supplement their diets with antioxidant and immuno-stabilizing micronutrients, such as selenium, vitamin C, and vitamin D, often without the knowledge of the treating physician. From the oncological viewpoint, there are justifiable concerns that dietary supplements decrease the effectiveness of chemotherapy and radiotherapy. Recent studies, however, have provided increasing evidence that treatment is tolerated better—with an increase in patient compliance and a lower rate of treatment discontinuations—when micronutrients, such as selenium, are added as appropriate to the patient’s medication. Nutritional supplementation tailored to an individual’s background diet, genetics, tumor histology, and treatments may yield benefits in subsets of patients. Clinicians should have an open dialogue with patients about nutritional supplements. Supplement advice needs to be individualized and come from a credible source, and it is best communicated by the physician

The increased adhesion of tumor cells to endothelial cells after irradiation can be reduced by FAK-inhibition

$\bf Background:$ Radiotherapy is administered in more than 60% of all solid tumors. Most patients are cured but a significant number develops local recurrences or distant metastases. The question arises if irradiation might influence the metastatic process. In the present study we examined whether the adhesion of glioblastoma or breast cancer cells to endothelial cells, an important step in metastasis, is affected by photon irradiation. $\bf Methods:$ U-87 MG, U-373 MG and MDA-MB-231 cancer cells as well as primary human endothelial cells were irradiated with 0, 2, 4, or 8 Gy photons at a dose rate of 5 Gy/min. The adhesion of cancer cells to endothelial cells was tested either with the Vybrant based assay via fluorescent labelling or with an ibidi pump system able to mimic the physiological blood flow in vitro. In addition, the impact of FAK (focal adhesion kinase) inhibitor PF-573, 228 on the adhesion of nonirradiated and irradiated tumor cells was analyzed. Adhesion related and regulated proteins were analyzed by Western blotting. $\bf Results:$ The cellular adhesion was increased after irradiation regardless of which cell type was irradiated. The FAKinhibitor was able to reduce the adhesion of non-irradiated cells but also the irradiation-induced increase in adhesion of tumor cells to endothelium. Adhesion related proteins were enhanced after irradiation with 4 Gy or 8 Gy in both cells types. The increased adhesion after irradiation is accompanied by the phosphorylation of src (Y416), FAK (Y397) and increased expression of paxillin. $\bf Conclusion:$ Irradiation with photons in therapeutic doses is able to enhance the interaction between tumor cells and endothelial cells and by that might influence important steps of the metastatic process

The increased motility of U-87 MG cells compared to U-373 MG cells appears to correlate with a low expression of Robo1 and Slit2.

<p>(A) Survival curve of glioblastoma cells after irradiation. The cells were irradiated with up to 8 Gy. (B) Quantification of Robo1-, Slit2-mRNA expression by qPCR. Values represent means ± standard deviation and are relative to the expression of the housekeeping gene GAPDH (100%). ****p<0.0001, **p<0.01 (Student t-test). (C) Motility of non-irradiated U-373 MG and U-87 MG cells. Cell motility was measured by the parameters velocity, Euclidean distance, and accumulated total distance. Data shown are means ± standard error. ***p<0.001 (Mann-Whitney U test).</p

Semiquantitive immunoblot analyses.

<p>The expression of vimentin (A, E-G), fascin (B, H-J), focal adhesion kinase (FAK) (C, K-M), and phosphorylated focal adhesion kinase (pFAK^Y925) (D, N-P) was quantified in U-373 MG wild-type cells and clones overexpressing Slit2 or Robo1 and the effect of photon irradiation on their expression was assessed. Proteins were isolated 24h after irradiation. WT, U-373 MG wild-type cells; Ctrl, U-373 MG control cells (transfected with empty vector); Robo1, U-373 MG-Robo1 (stable clone overexpressing Robo1); Slit2, U-373 MG-Slit2 (stable clone overexpressing Slit2).</p

Motility of U-373 MG cells after Robo1-downregulation by siRNA.

<p>(A) Western blot assay demonstrating the downregulation of Robo1. WT, untreated control cells; siMock, siRobo1, cells transfected with control or Robo1-specific siRNAs. (B) The motility parameters velocity, accumulated distance, and Euclidean distance were determined in non-irradiated (0 Gy), Robo1-knockdown, and control U-373 MG cells and in Robo1-knockdown cells irradiated with a dose of 2 Gy. Data represent means ± standard errors. **p<0.01, *p<0.05 (Mann-Whitney U test).</p