3D in vivo dosimetry of HDR gynecological brachytherapy using micro silica bead TLDs.

PURPOSE: This study aimed to evaluate the feasibility of defining an in vivo dosimetry (IVD) protocol as a patient-specific quality assurance (PSQA) using the bead thermoluminescent dosimeters (TLDs) for point and 3D IVD during brachytherapy (BT) of gynecological (GYN) cancer using 60 Co high-dose-rate (HDR) source. METHODS: The 3D in vivo absorbed dose verification within the rectum and bladder as organs-at-risk was performed by bead TLDs for 30 GYN cancer patients. For rectal wall dosimetry, 80 TLDs were placed in axial arrangements around a rectal tube covered with a layer of gel. Ten beads were placed inside the Foley catheter to get the bladder-absorbed dose. Beads TLDs were localized and defined as control points in the treatment planning system (TPS) using CT images of the patients. Patients were planned and treated using the routine BT protocol. The experimentally obtained absorbed dose map of the rectal wall and the point dose of the bladder were compared to the TPSs predicted absorbed dose at these control points. RESULTS: Relative difference between TPS and TLDs results were -8.3% ± 19.5% and -7.2% ± 14.6% (1SD) for rectum- and bladder-absorbed dose, respectively. Gamma analysis was used to compare the calculated with the measured absorbed dose maps. Mean gamma passing rates of 84.1%, 90.8%, and 92.5% using the criteria of 3%/2 mm, 3%/3 mm, and 4%/2 mm were obtained, respectively. Eventually, a "considering level" of at least 85% as pass rate with 4%/2-mm criteria was recommended. CONCLUSIONS: A 3D IVD protocol employing bead TLDs was presented to measure absorbed doses delivered to the rectum and bladder during GYN HDR-BT as a reliable PSQA method. 3D rectal absorbed dose measurements were performed. Differences between experimentally measured and planned absorbed dose maps were presented in the form of a gamma index, which may be used as a warning for corrective action.

Validation of an individualized home-made superficial brachytherapy mold applied for deep nonmelanoma skin cancer.

Background: This study was conducted to evaluate the effect of brachytherapy (BT) customized mold [Condensation silicone elastomer (ProtesilTM)] and its thickness on the dose distribution pattern of deep nonmelanoma skin cancers (NMSC). Materials and methods: Four blocks of mold material were constructed in 5, 10, 15, and 20 mm thickness and 100 × 100 mm2 area by a plastic cast. The high dose rate (HDR) plus treatment planning system (TPS) (Version 3, Eckert & Ziegler BEBIG Gmbh, Berlin, Germany) with a 60Co source (model: Co0.A86, EZAG BEBIG, Berlin, Germany) as an high dose rate brachytherapy (HDR-BT) source was used. Solid phantom and MOSFETTM and GAFCHROMICTM EBT3 film dosimeters were used for experimental dosimetry of the different thicknesses (up to 20 mm) of BT customized mold. Skin dose and dose to different depths were evaluated. Result: The TPS overestimated the calculated dose to the surface. Skin dose can be reduced from 250% to 150% of the prescription dose by increasing mold thickness from 5 mm to 20 mm. There was a 7.7% difference in the calculated dose by TPS and the measured dose by MOSFET. There was a good agreement between film dosimetry, MOSFET detector, and TPS' results in depths less than 5 mm. Conclusion: Each BT department should validate any individualized material chosen to construct the customized surface BT mold. Increasing the mold thickness can treat lesions without overexposing the skin surface. Superficial BT can be recommended as an appropriate treatment option for some deep NMSC lesions (up to 20 mm) with pre-planning considerations employing thicker molds.

Investigating the effect of radiosensitizer for Ursolic Acid and Kamolonol Acetate | on HCT-116 cell line.

PURPOSE: The aim of this study was evaluating the cytotoxic and radiosensitizing effects of Ursolic Acid (UA) and Kamolonol Acetate (KA) on HCT116 cell line and finally investigating the functional role of NF-κB and CCND1 genes in the radiosensitizing activity of UA and KA. MATERIALS AND METHOD: The cytotoxic effects of UA and KA by MTT assay was evaluated on HCT-116. Clonogenic assay was performed to investigate of radiosensitizing effects of UA and KA on HCT116. To assessment the expression levels of NF-κB and CCND1 genes, real-time PCR method was used. RESULTS: The results of MTT assay revealed that UA and KA have cytotoxic effects on HCT116 cell line. According to clonogenic assay, survival fraction of treated cells with UA and KA has been decreased compared to the survival fraction of untreated cells. UA and KA lead to the decrease in the expression level of NF-κB. Synergistic effect of radiosensitizing agents with radiation was only approved for UA and 2 Gy of radiation. CONCLUSION: Based on our study, UA and KA have cytotoxic effects on HCT116 cell line. Furthermore, UA may lead to radiosensitization of human colorectal tumor cells by NF-κB1 and CCND1signaling pathways.

Let-7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin-like growth factor 1 receptor.

Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let-7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let-7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin-like growth factor 1 receptor (IGF-1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF-1R is a direct target of the let-7e member. Consistent with this, we identified that increased levels of let-7e in CRC cells reduced IGF-1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let-7e by targeting the IGF-1R signaling pathway might serve as therapeutics in anticancer therapy.

Investigation of Collapsed-cone Algorithm Accuracy in Small Fields and Heterogeneous Environments.

BACKGROUND: The use of small fields has increased by the emergence of advanced radiotherapy. Dose calculations of these fields are complex and challenging for many reasons such as lack of electrical equilibrium even in homogeneous environments, and this complexity will increase in presence of heterogeneity. According to the importance of delivery the accurate prescription dose to the target volume in the patient's body, the dose calculation accuracy of used commercial algorithms in clinical treatment planning systems (TPS) should be evaluated. OBJECTIVE: The present study aims to evaluate the accuracy of Collapsed-cone dose measurement algorithm in Isogray treatment planning system. MATERIAL AND METHODS: In this analytical study, the measurements were made in tissue equivalent solid water phantom with lung and bone heterogeneities by Pinpoint dosimeter (0.015 cm3 sensitive volume) in several radiation fields (1×1 to 5×5 cm2). The phantoms were irradiated with 6, 10 and 18 MV photon beams and finally, the results of experimental calculations were compared with treatment planning outputs. RESULTS: In all setups, the maximum deviation occurred in the field of 1×1 cm2. Then, the maximum deviation was observed for 2×2 cm2 field size; however, it was up to 5% for homogeneous water phantom and lung heterogeneity. In 3×3 cm2 and larger fields, there was a good agreement between the results of the TPS and experimental dosimetry. The maximum deviation was observed in water-bone heterogeneity. CONCLUSION: This algorithm was able to pass the standard audit criteria, but it is better to be used more cautiously in bone heterogeneity, especially in low energies.

A Randomized, Controlled, Parallel-Group, Trial on the Effects of Melatonin on Fatigue Associated with Breast Cancer and Its Adjuvant Treatments.

OBJECTIVE: Fatigue associated with malignant conditions and their treatments is a disabling condition. This trial assessed the anti-fatigue effects of melatonin coadministration during adjuvant treatment of patients with the breast cancer. MATERIAL AND METHODS: Patients with breast cancer were randomly assigned to receive melatonin or placebo during adjuvant chemotherapy and radiotherapy. Thirty-seven patients were randomly enrolled in each group. The mean ages of patients in the intervention and control groups were 50.47 ± 10.79 and 46.05 ± 10.55 years, respectively (P = .223). The intervention group received oral melatonin (18 mg/day) from 1 week before until 1 month after the adjuvant radiotherapy. The level of fatigue was assessed before and after intervention using Brief Fatigue Inventory (BFI) in both groups. To analyze data, the Student's t-test and the Chi-square test were used at a significance level of P ≤ .05. RESULTS: The BFI score was similar before the intervention in both groups, however, after the intervention, it was significantly lower in the melatonin group (P < .001). Moreover, the frequency of severe fatigue in the melatonin group was significantly lower than in the placebo group after intervention (42.1% vs 83.3%, P < .001). CONCLUSION: Coadministration of melatonin during adjuvant chemotherapy and radiotherapy of women with breast cancer decreased the levels of fatigue associated with the malignant condition and its treatments.

DCLK1 Inhibition Sensitizes Colorectal Cancer Cells to Radiation Treatment.

Colorectal cancer (CRC) is one of the most prevalent diagnosed cancers and a common cause of cancer-related mortality. Despite effective clinical responses, a large proportion of patients undergo resistance to radiation therapy. Therefore, the identification of efficient targeted therapy strategies would be beneficial to overcome cancer radioresistance. Doublecortin-like kinase 1 (DCLK1) is an intestinal and pancreatic stem cell marker that showed overexpression in a variety of cancers. The transfection of DCLK1 siRNA to normal HCT-116 cells was performed, and then cells were irradiated with X-rays. The effects of DCLK1 inhibition on cell survival, apoptosis, cell cycle, DNA damage response (ATM and γH2AX proteins), epithelial-mesenchymal transition (EMT) related genes (vimentin, N-cadherin, and E-cadherin), cancer stem cells markers (CD44, CD133, ALDH1, and BMI1), and ß-catenin signaling pathway (ß-catenin) were evaluated. DCLK1 siRNA downregulated DCLK1 expression in HCT-116 cells at both mRNA and protein levels (P <0.01). Colony formation assay showed a significantly reduced cell survival in the DCLK1 siRNA transfected group in comparison with the control group following exposure to 4 and 6 Gy doses of irradiation (P <0.01). Moreover, the expression of cancer stem cells markers (P <0.01), EMT related genes (P <0.01), and DNA repair proteins including pATM (P <0.01) and γH2AX (P <0.001) were significantly decreased in the transfected cells in comparison with the nontransfected group after radiation. Finally, the cell apoptosis rate (P <0.01) and the number of cells in the G0/G1 phase in the silencing DCLK1 group was increased (P <0.01). These findings suggest that DCLK1 can be considered a promising therapeutic target for the treatment of radioresistant human CRC.

Influence of dwell time homogeneity error weight parameter on treatment plan quality in inverse optimized high-dose-rate cervix brachytherapy using SagiPlan.

PURPOSE: Restricting the gradients of dwell times between adjacent dwell positions can potentially be beneficial in reducing the probability of unwanted hot/cold spots occurring, if the planned applicators/anatomy relative positions change before or during treatment. This constraint, however, may degrade plan quality. This study, for the first time, aims to quantify the impact of modulation restriction on plan quality indices in inverse optimization for cervix high-dose-rate (HDR) brachytherapy using the BEBIG SagiPlan treatment planning system. MATERIAL AND METHODS: Ten cervical cancer patient plans were optimized for treatment with a BEBIG SagiNova 60Co HDR afterloader using the min/max inverse planning method, with dwell time homogeneity error weight (DTHEW) parameter values of 0 to 10. Dwell time homogeneity and gradients as well as various plan quality indices were analyzed. RESULTS: For DTHEW = 0, min/max-based optimization yielded higher HR-CTV D90 values than the variance-based option (p < 0.001) and was therefore selected for this study. Averaging over all patients, selecting non-zero DTHEWs resulted in a general increase in dwell time homogeneity and decrease in mean and maximum adjacent dwell time gradients, especially between DTHEWs of 0 and 1. For DTHEW > 1, an increase of this parameter did not always result in more homogeneous dwell times or reduced gradients in individual patients. There was a negative correlation between DTHEW and both HR-CTV D90 and V100 (p < 0.001, r = -0.91). Increasing DTHEW also negatively affected conformity index (p < 0.001, r = -0.99). Changes in rectum and sigmoid colon D2cc were insignificant. There was a strong positive relationship between bladder D2cc and DTHEW (p < 0.001, r = 0.99). CONCLUSIONS: Assuming a static geometry, statistically significant degradation of plan quality can result from restricting the dwell time homogeneity in min/max-based optimization of cervix HDR brachytherapy plans using SagiPlan. Therefore, setting DTHEW to zero is indicated for the type of patient plans considered in this study.

MiR-185 enhances radiosensitivity of colorectal cancer cells by targeting IGF1R and IGF2.

OBJECTIVE: Radioresistance is a significant obstacle for effective treatment of colorectal cancer (CRC). Recent studies have indicated that miR-185 inhibits proliferation, survival, and invasion of CRC; however, the role of this miRNA in radioresistance of CRC has not been identified yet. The aim of this study is to investigate the role of miR-185 in radiosensitivity of CRC. METHODS: After transfecting the cells with mimic miR-185, expressions of IGF1R and IGF2 were evaluated by real-time PCR and western blot. The radiation response of transfected cells was also examined by colony forming assay. Sub-G1 fraction analysis through flow cytometry and caspase 3 activity was used to evaluate apoptosis. RESULTS: The results of real-time PCR and western blot indicated that IGF1R and IGF2 are downregulated in the transfected cells. Colony forming assay revealed that transfected cells were more radiosensitive than other cells. On the other hand,following irradiation the rate of apoptosis was significantly higher in the transfected cells than in the other cells. CONCLUSION: In summary, our study is the first to show that upregulation of miR-185 enhances the sensitivity of CRC cells to ionizing radiation. miR-185 may act as a novel biomarker of radioresistance and may clinically enhance the radiation response of CRC.

Involvement of miR-155/FOXO3a and miR-222/PTEN in acquired radioresistance of colorectal cancer cell line.

PURPOSE: Finding a novel biomarker for determining the radiosensitivity of colorectal cancer (CRC) is critical. The aim of this study is to evaluate the role of two main miRNAs including miR-222 and miR-155 in radiation response of CRC. MATERIALS AND METHODS: The radioresistant CRC cell lines were established by exposing the HCT 116 cell line to fractional X-ray radiation. SubG1 fraction analysis, MTT and clonogenic assays were applied to evaluate acquired radioresistant cell line radiosensitivity. miR-222/PTEN and miR-155/FOXO3a expressions were detected by RT PCR. RESULTS: The clonogenic assay and sub-G1fraction analysis indicated that the RR2 sub-line was significantly more resistant than the parental cell line. MiR-222 and miR-155 were significantly upregulated in the radioresistant cell lines compared with the parental cell lines. The PTEN and FOXO3a expressions in the radioresistant cell lines were significantly higher than in the parental line. CONCLUSION: These observations indicate that miR-222 and miR-155 could induce radiation resistance in colorectal cancer by targeting PTEN and FOXO3a genes, respectively. Therefore, miR-222 and miR-155 can be suggested as good biomarkers of CRC radiation response.