Evaluation of an EPID in vivo monitoring system using local and external independent audit measurements.

PURPOSE: The aim of this work was to evaluate the SunCHECK PerFRACTION, the software for in vivo monitoring using EPID images. MATERIALS/METHODS: First, the PerFRACTION ability to detect errors was investigated simulating two situations: (1) variation of LINAC output and (2) variation of the phantom thickness. An ionization chamber was used as reference to measure the introduced dose variations. Both tests used EPID in integrated mode (absolute dose). Second, EPID measurements in integrated mode were carried out during an independent Brazilian governmental audit that provided four phantoms and TLDs. PerFRACTION calculated the absolute dose on EPID plane, and it compared with predicted calculated dose for every delivered plan. The dose deviations reported using PerFRACTION were compared with dose deviations reported by the independent audit. Third, an end-to-end test using a heterogeneous phantom was performed. A VMAT plan with EPID in cine mode was delivered. PerFRACTION calculated the mean dose on CBCT using EPID information and log files. The calculated doses at four different points were compared with ionization chambers measurements. RESULTS: About the first test, the largest difference found was 1.2%. Considering the audit results, the variations detected by TLD measurements and by PerFRACTION dose calculation on EPID plane were close: 12 points had variations less than 2%, 2 points with variation between 2% and 3%, and 2 points with deviations greater than 3% (max 3.7%). The end-to-end tests using a heterogeneous phantom achieved dose deviation less than 1.0% in the water-equivalent region. In the mimicking lung region, the deviations were higher (max 7.3%), but in accordance with what is expected for complex situations. CONCLUSION: The tests results indicate that PerFRACTION dose calculations in different situations have good agreement with standard measurements. Action levels were suggested for absolute dose on EPID plane as well as 3D dose calculation on CBCT using PerFRACTION.

Additive cytotoxic effects of radiation and mTOR inhibitors in a cervical cancer cell line.

The PI3K/AKT/mTOR signaling pathway is frequently activated in HPV-positive cervical squamous cell cancer (CC). This study investigated the biological effects of mTOR inhibitors associated with radiotherapy in a CC cell line (HeLa). A human keratinocyte cell line (HaCaT) was used as control. Temsirolimus, everolimus, resveratrol, curcumin and epigallocatechin gallate (EGCG) were the mTOR inhibitors assessed. The 50% cell cytotoxicity rate (CC50) for each treatment was determined by MTT cell viability assay. Cells were pre-treated with mTOR inhibitors at CC50 followed by radiotherapy (RT) at 2Gy. Cell death profile after treatment with temsirolimus, resveratrol and curcumin was assessed with flow cytometry. Everolimus, temsirolimus, EGCG, resveratrol and curcumin were cytotoxic to HeLa. Radiation induced a statistically significant (p<0.01) supra-additive cytotoxic effect in the cervical cancer cell line when combined with mTOR inhibitors. After a 24-h treatment, EGCG and resveratrol were more cytotoxic to HeLa cells than to HaCaT cells. After 48h of treatment, resveratrol, curcumin and everolimus were more cytotoxic to HeLa cells when compared to HaCaT cells. After 24h, temsirolimus induced late apoptosis or necrosis in HeLa cells. Based on these data, new studies with mTOR inhibitors as treatment options for cervical cancer are recommended, mainly combined to radiotherapy.

Gel of chamomile vs. urea cream to prevent acute radiation dermatitis in patients with head and neck cancer: a randomized controlled trial.

AIM: To compare a gel made with chamomile (Chamomilla recutita) with a cream of urea as an intervention to delay the time to occurrence of radiation dermatitis. BACKGROUND: Radiation dermatitis is one of the most common adverse effects of radiotherapy in patients with head and neck cancer. It is characterized by erythema, itching, pain, skin breakage and burning sensation, and there is no consensus on how to prevent it. DESIGN: The study is a randomized controlled clinical trial. METHODS: We will recruit 48 individuals with head and neck cancer who will be starting their radiotherapy and randomize them to receive either gel of chamomile or cream of urea, as an intervention for prevention of radiation dermatitis. Social-demographic data will be collected at baseline, and clinical data will be collected before the initiation of radiotherapy. Participants will be followed weekly to assess development of radiation dermatitis. The protocol is funded by Conselho Nacional de Pesquisa e Desenvolvimento Científico (Brazil). The study was approved by a research ethics committee. DISCUSSION: Given the clinical relevance of preventing radiation dermatitis and the lack of evidence supporting specific preventive interventions, it is important to study new products that might be efficacious to prevent this complication. This article presents the protocol of a randomized controlled trial comparing a gel made with chamomile (intervention) with a cream of urea (control) to prevent radiation dermatitis in patients with head and neck cancer undergoing radiotherapy.

Combined paclitaxel, cisplatin and fluorouracil therapy enhances ionizing radiation effects, inhibits migration and induces G0/G1 cell cycle arrest and apoptosis in oral carcinoma cell lines.

Although taxels (in particular paclitaxel), cisplatin and fluorouracil (TPF) chemotherapy has been approved for use in the treatment of head and neck squamous cell carcinoma (HNSCC), little is known with regard to the cellular mechanisms of this novel drug association. In order to investigate the reaction of cells to this novel treatment, the present study aimed to examine the cytotoxic effect of TPF in HNSCC cell lines in combination with irradiation, to analyze its effect on cell cycle progression and cell death, and to evaluate its ability to alter cell migration. An MTT assay was used to determine cell viability following TPF and cisplatin treatments in two human HNSCC cell lines (FaDu and SCC-9) and one keratinocyte cell line (HaCaT). The concurrent use of TPF or cisplatin and irradiation was also analyzed. Flow cytometric analysis was utilized to determine the cell cycle distribution and to verify the induction of apoptosis. The capacity of the drugs to alter oral cancer cell migration was also evaluated using a Transwell migration assay. The results indicated that TPF and cisplatin were cytotoxic to all cell lines, and enhanced the effects of ionizing radiation. FaDu cells were significantly more sensitive to the two treatments, and TPF was more cytotoxic than cisplatin for all cells. Flow cytometric analysis revealed that TPF increased the number of cells in G0/G1 phase in the SCC-9 cell line, and indicated apoptotic cell death. The results of the Transwell assay demonstrated that TPF inhibited migration in oral carcinoma cell lines. The results of the present study indicated that TPF functions in oral carcinoma cell lines through the enhancement of ionizing radiation effects, inducing cell cycle arrest at G0/G1 and apoptosis, in addition to inhibiting migration.

Use of 3D-printers to create intensity-modulated radiotherapy compensator blocks.

Intensity-Modulated Radiotherapy (IMRT) is an important tool for cancer treatment. It concentrates high radiation doses in complex target volumes, while sparing the surrounding tissues. IMRT is traditionally performed using Multileaf Collimators (MLC) or Compensator Blocks. The conventional way used to manufacture IMRT compensator blocks, which uses milling machines, is an important drawback over the MLC method, due to high operational and production costs. In this research, we developed a simpler alternative method to manufacture an IMRT compensator block from a fluency map generated by a commercial treatment planning system (TPS). This map was converted into a mold, and then printed using a 3D printer. The final IMRT compensator block was achieved by filling the mold with cerrobend alloy. To validate this method a quality assurance was performed using dosimetric films to compare the measured dose distributions to those predicted by the TPS system. This comparison showed a good agreement among 8 dose profiles from each situation, with a maximum RMS error of 8.84 % for the tested profiles. This suggests that the 3D printers can be effectively used to manufacture IMRT compensator blocks. The main advantage to this approach is that it can be fully conducted inside a radiotherapy facility, which results in lower costs and production times.