A Promising, Novel Radiosensitizer Nanodrug Complex for Oral Cavity Cancer: Cetuximab and Cisplatin-Conjugated Gold Nanoparticles.

BACKGROUND: Nanomedicine has provided promising tools for the imaging, diagnosis, and treatment of cancer. Gold nanoparticles (GNPs) may be useful in enhancing the efficacy of radiotherapy, such as radiosensitization, in cancer therapy. AIMS: To develop a nanodrug complex containing cetuximab (C225,CTX) and cisplatin (CDDP) conjugated with GNPs and to investigate its cytotoxic effects on oral cavity cancer cells when combined with radiotherapy. STUDY DESIGN: In vitro cell culture study. METHODS: The GNPs were synthesized and successfully conjugated with cetuximab and cisplatin. Cell viability was monitored by the xCELLigence real-time cell analysis (RTCA) single-plate (SP) system in GNP-treated UPCI-SCC-131 cells for 48 hours. Cells with/without GNPs were irradiated with 6 MV X-rays, and colony formation was assayed to investigate the long-term effects of GNPs and the nanodrug complex after irradiation on radiotherapy-resistant oral cavity cancer cells. RESULTS: The GNPs entered the tumor cells, and GNP-CDDP (P <.0001) and GNP-CDDP-CTX (P < .0001) were shown to cause a decrease in cell viability. GNP and GNP-CTX combined with radiotherapy led to greater reduction on UPCI-SCC-131 colony numbers, than radiation alone (P = .0369) and radiation with free CTX, with sensitizing enhancement ratios of 1 : 2 and 1 : 9, respectively. CONCLUSION: The cetuximab and cisplatin-conjugated gold nanodrug complex has a great potential to increase cytotoxicity and overcome resistance to radiotherapy, in the treatment of oral cavity cancer.

The importance of mesorectum motion in determining PTV margins in rectal cancer patients treated with neoadjuvant radiotherapy.

New precision radiotherapy (RT) techniques reduce the uncertainties in localizing soft and moving tumors. However, there are still many uncontrollable internal organ movements. In our study, patients who underwent neoadjuvant chemoradiotherapy (NA-CRT) for rectal cancer were evaluated to determine inter-fraction mesorectum motion and dosimetric changes. Fourteen patients treated with NA-CRT for rectal cancer between 2014 and 2016 were included in the analysis. The mesorectum and clinical target volume (CTV) were delineated on planning computed tomography (CT) and cone-beam CT (CB-CT) scans. After planning with a volumetric modulated arc therapy (VMAT) plan, re-planning was performed on all CB-CTs. Finally, the volumetric and dosimetric changes of PTV and mesorectum were evaluated in all CB-CTs compared with the initial CT and VMAT plans. The geometrical center of mesorectum volume in CB-CTs had moved 1 (0.2-6.6), 1.6 (0.2-3.8) and 1.6 (0-4.9) mm in the x, y and z-axis respectively compared with the initial CT. The dosimetric parameters of PTV including D2, D95 and D98 on CB-CT showed a median 47.19 (46.70-47.80), 45.05 (44.18-45.68) and 44.69 (43.83-45.48) Gy and median 1% (1-2), 0% (0-2) and 1% (0-2) dosimetric change compared with the initial VMAT plan. In our study, we have shown that the mesorectum has moved up to 20 mm in the lateral and anterior-posterior direction and almost 10 mm in the superior/inferior direction during RT, causing a median of ~2% change in dosimetric parameters. Therefore, these movements must be considered in determining PTV margins to avoid dosimetric changes.

A heart atlas for breast radiation therapy and the influence of delination education on both intra and interobserver variability.

PURPOSE: We developed a heart atlas for breast radiation therapy and evaluated the influence of education on intra and inter-observer similarity, and cardiac dose reporting. MATERIALS AND METHODS: The data of 16 left breast cancer patients were analyzed. Eight observers delineated heart and cardiac subunits [left (LCA) and right (RCA) coronary arteries, left anterior descending artery (LAD), bilateral atrium and ventricles] before the education. A radiologist and radiation oncologist developed the atlas and delineated the gold standard (GS) volumes. Observers repeated the delineation after education. RT plans were made for pre/post-atlas contours. The similarity was assessed by Dice (DSC) and Jaccard (JSC) similarity coefficient indices. The absolute difference rate was calculated for the dose analysis. RESULTS: The inter-observer similarity increased in heart and all subunits. The intra-observer similarity showed a heterogeneous distribution. The absolute difference rate in dose reporting was statistically significant for the bilateral atrium, right ventricle, LAD, LCA + LAD, RCA's maximum doses (p < 0.05). The maximum dose reporting differences from the GS decreased from 16.9 to 8.9% for LAD (p = 0.011); from 14.8 to 9.3% for LCA + LAD (p = 0.010). CONCLUSION: The cardiac atlas reduces the intra-interobserver differences and improves dose reporting consistency. The first intra-observer similarity analysis was made in our study and revealed the need for repeated education to increase the consistency.