The impact of intraoperative radiotherapy on breast cancer: focus on the levels of angiogenic factors.

OBJECTIVE: Angiogenesis is one of the hallmarks of cancers that is involved in tumor progression. Angiogenic factors induce the formation of new blood vessels and tumor extension, and finally reduce the survival of patients. Intraoperative radiotherapy (IORT), in which radiation is delivered to the tumor bed can kill cells and change tumor microenvironment. Here, we compared the impact of IORT on the levels of angiogenic factors in the blood and surgical wound fluids (SWF) of the breast cancer patients. PATIENTS AND METHODS: Three hundred sixty patients, who had undergone breast-conserving surgery between 2013 and 2018, were enrolled in IORT and non-IORT groups non-randomly. Blood and drained wound fluid (WF) samples were collected from the patients before and after surgery, followed by quantification of the amounts of TGF-ß, EGF, FGF, VEGF, and DLL4 in the patients using ELISA. RESULTS: Our results were indicative of significant differences between the pre-surgery and post-surgery serum levels of EGF, DLL4, and VEGF. Furthermore, ROC analyses showed that TGF-ß and DLL4 can differentiate of the early-stage from late-stage of the disease. Interestingly, the rate of the death and recurrence was reduced in IORT group. CONCLUSIONS: In summary, IORT is a safe and effective treatment that can affect angiogenic factors and improve the overall- and recurrence-free survival of breast cancer patients.

Potential advantages of FDG-PET radiomic feature map for target volume delineation in lung cancer radiotherapy.

PURPOSE: To investigate the potential benefits of FDG PET radiomic feature maps (RFMs) for target delineation in non-small cell lung cancer (NSCLC) radiotherapy. METHODS: Thirty-two NSCLC patients undergoing FDG PET/CT imaging were included. For each patient, nine grey-level co-occurrence matrix (GLCM) RFMs were generated. gross target volume (GTV) and clinical target volume (CTV) were contoured on CT (GTVCT , CTVCT ), PET (GTVPET40 , CTVPET40 ), and RFMs (GTVRFM , CTVRFM ,). Intratumoral heterogeneity areas were segmented as GTVPET50-Boost and radiomic boost target volume (RTVBoost ) on PET and RFMs, respectively. GTVCT in homogenous tumors and GTVPET40 in heterogeneous tumors were considered as GTVgold standard (GTVGS ). One-way analysis of variance was conducted to determine the threshold that finds the best conformity for GTVRFM with GTVGS . Dice similarity coefficient (DSC) and mean absolute percent error (MAPE) were calculated. Linear regression analysis was employed to report the correlations between the gold standard and RFM-derived target volumes. RESULTS: Entropy, contrast, and Haralick correlation (H-correlation) were selected for tumor segmentation. The threshold values of 80%, 50%, and 10% have the best conformity of GTVRFM-entropy , GTVRFM-contrast , and GTVRFM-H-correlation with GTVGS , respectively. The linear regression results showed a positive correlation between GTVGS and GTVRFM-entropy (r = 0.98, p < 0.001), between GTVGS and GTVRFM-contrast (r = 0.93, p < 0.001), and between GTVGS and GTVRFM-H-correlation (r = 0.91, p < 0.001). The average threshold values of 45% and 15% were resulted in the best segmentation matching between CTVRFM-entropy and CTVRFM-contrast with CTVGS , respectively. Moreover, we used RFM to determine RTVBoost in the heterogeneous tumors. Comparison of RTVBoost with GTVPET50-Boost MAPE showed the volume error differences of 31.7%, 36%, and 34.7% in RTVBoost-entropy , RTVBoost-contrast , and RTVBoost-H-correlation , respectively. CONCLUSIONS: FDG PET-based radiomics features in NSCLC demonstrated a promising potential for decision support in radiotherapy, helping radiation oncologists delineate tumors and generate accurate segmentation for heterogeneous region of tumors.

Suberosin Attenuates the Proliferation of MCF-7 Breast Cancer Cells in Combination with Radiotherapy or Hyperthermia.

AIM: The aim of this study was to determine the proliferation of MCF-7 following irradiation or hyperthermia as alone or pre-treatment with suberosin. BACKGROUND: Radiotherapy is a major therapeutic modality for the control of breast cancer. However, hyperthermia can be prescribed for relief of pain or enhancing cancer cell death. Some studies have attempted its use as an adjuvant to improve therapeutic efficiency. Suberosin is a cumarin- derived natural agent that has shown anti-inflammatory properties. OBJECTIVE: In this in vitro study, possible sensitization effect of suberosin in combination with radiation or hyperthermia was evaluated. METHODS: MCF-7 breast cancer cells were irradiated or received hyperthermia with or without treatment with suberosin. The incidence of apoptosis as well as viability of MCF-7 cells were observed. Furthermore, the expressions of pro-apoptotic genes such as Bax, Bcl-2, and some caspases were evaluated using real-time PCR. RESULTS: Both radiotherapy or hyperthermia reduced the proliferation of MCF-7 cells. Suberosin amplified the effects of radiotherapy or hyperthermia for induction of pro-apoptotic genes and reducing cell viability. CONCLUSION: Suberosin has a potent anti-cancer effect when combined with radiotherapy or hyperthermia. It could be a potential candidate for killing breast cancer cells as well as increasing the therapeutic efficiency of radiotherapy or hyperthermia.

Resveratrol Induces Apoptosis and Attenuates Proliferation of MCF-7 Cells in Combination with Radiation and Hyperthermia.

AIM: In the current in vitro study, we tried to examine the possible role of resveratrol as a sensitizer in combination with radiotherapy or hyperthermia. BACKGROUND: Breast cancer is the most common malignancy for women and one of the most common worldwide. It has been suggested that using non-invasive radiotherapy alone cannot eliminate cancer cells. Hyperthermia, which is an adjuvant modality, induces cancer cell death mainly through apoptosis and necrosis. However, cancer cells can also develop resistance to this modality. OBJECTIVE: The objective of this study was to determine possible potentiation of apoptosis when MCF-7 cells treated with resveratrol before hyperthermia or radiotherapy. METHODS: MCF-7 cancer cells were treated with different doses of resveratrol to achieve IC50%. Afterwards, cells treated with the achieved concentration of resveratrol were exposed to radiation or hyperthermia. Proliferation, apoptosis and the expression of pro-apoptotic genes were evaluated using flow cytometry, MTT assay and real-time PCR. Results for each combination therapy were compared to radiotherapy or hyperthermia without resveratrol. RESULTS: Both irradiation or hyperthermia could reduce the viability of MCF-7 cells. Furthermore, the regulation of Bax and caspase genes increased, while Bcl-2 gene expression reduced. Resveratrol potentiated the effects of radiation and hyperthermia on MCF-7 cells. CONCLUSION: Results of this study suggest that resveratrol is able to induce the regulation of pro-apoptotic genes and attenuate the viability of MCF-7 cells. This may indicate the sensitizing effect of resveratrol in combination with both radiotherapy and hyperthermia.

Evaluating the effectiveness of combined radiotherapy and hyperthermia for the treatment response of patients with painful bony metastases: A phase 2 clinical trial.

INTRODUCTION: Since the survival time of patients with bony metastases has noticeably improved in recent years, these patients are at high risk of complications associated with this metastasis. Hence, the appropriate choice of treatment modality or combination of therapeutic approaches can lead to increasing bone pain relief, improving quality of life, etc. This study is aimed to evaluate the effectiveness of combined radiotherapy and hyperthermia for the treatment response of patients with painful bony metastases. PATIENTS AND METHODS: In a single-arm clinical trial, 23 eligible patients (14 female and 9 male) with the mean age of 67 years old and suffering from bony metastases were enrolled in the study. Two hours after radiotherapy, the patients underwent hyperthermia for 1 h in the supine position. All the patients completed the brief pain inventory (BPI) assessment tool and quality of life questionnaire (QLQ-C30) from the European Organization for Research and Treatment of Cancer (EORTC) at the baseline, end of the treatment and 1, 2 and 3 months thereafter. The response to the treatment was assessed as the zero score (complete response) or two or more than two-point drop of the worst pain within the preceding 24 h (partial response) during the 3-month posttreatment. RESULTS: All the pain intensity and interference scores, except the pain interference with the enjoyment of life score, significantly decreased. A total of 18 out of 23 patients (78%) achieved complete or partial response. The number of patients using pain relief medications decreased from 74% (n=17) at the baseline to 48% (n=11) 3 months later. Moreover, except for nausea and vomiting, appetite loss, diarrhea and financial impact problems, the patients' quality of life improved significantly in all the functional scales and symptoms within 3 months. CONCLUSION: This study showed that using hyperthermia in combination with radiotherapy significantly ameliorated bone pain among the patients suffering from cancer with painful bony metastases.

Measurement of peripheral dose to the pelvic region and the associated risk for cancer development after breast intraoperative electron radiation therapy.

This study aimed to measure the received dose to the pelvic region of patients during breast intraoperative electron radiation therapy (IOERT). Furthermore, we compared the findings with those of external beam radiation therapy. Finally, secondary ovarian and uterus cancer risks following breast IOERT were estimated. In the current study, the received dose to the pelvic surface of 18 female patients during breast IOERT boosts were measured by thermoluminescent dosimeter (TLD-100) chips. All patients were treated with 12 Gy given in a single fraction. To estimate the dose to the ovary and uterus of the patients, conversion coefficients for depth from the surface dose were obtained in a Rando phantom. Given the received dose to the pelvic region of the patients, secondary ovarian and uterus cancer risks following breast IOERT were estimated. The received doses to the ovary and uterus surface of the patients were 0.260 ± 0.155 mGy to 31.460 ± 6.020 mGy and 0.485 ± 0.122 mGy to 22.387 ± 15.476 mGy, respectively. Corresponding intra-pelvic (ovary and uterus) regional doses were 0.012 ± 0.007 mGy to 1.479 ± 0.283 mGy and 0.027 ± 0.001 mGy to 1.164 ± 0.805 mGy, respectively. Findings demonstrated that the ratio of the received dose by the pelvic surface to the regional dose during breast IOERT was much less than external beam radiation therapy. The mean of the secondary cancer risks for the ovary in 8 and 10 MeV electron beam energies were 135.722 ± 117.331 × 10-6 and 69.958 ± 28.072 × 10-6, and for the uterus were 17.342 ± 10.583 × 10-6 and 2.971 ± 3.604 × 10-6, respectively. According to our findings, the use of breast IOERT in pregnant patients can be considered as a safe radiotherapeutic technique, because the received dose to the fetus was lower than 50 mGy. Furthermore, IOERT can efficiently reduce the unnecessary dose to the pelvic region and lowers the risk of secondary ovarian and uterus cancer following breast irradiation.

Dose response characteristics of a novel CCD camera-based electronic portal imaging device comparison with OCTAVIUS detector.

AIM: Dosimetric properties of a CCD camera-based Electronic Portal Imaging Device (EPID) for clinical dosimetric application have been evaluated. Characteristics obtained by EPID also compared with commercial 2D array of ion chambers. MATERIALS AND METHODS: Portal images acquired in dosimetry mode then exported raw fluence or uncorrected images were investigated. Integration time of image acquisition mode has adjusted on 1 s per frame. RESULTS: As saturation of camera of the EPID, dose response does not have linear behavior. The slight nonlinearity of the camera response can be corrected by a logarithmic expression. A fourth order polynomial regression model with coefficient of determination of 0.998 predicts a response to absolute dose values at less than 50 cGy. A field size dependent response of up to 7% (0.99-1.06) relative OCTAVIUS detector measurement was found. The EPID response can be fitted by a cubic regression for field size changes, yielded coefficient of determination of 0.999. CONCLUSIONS: These results indicate that the EPID is well suited for accurate dosimetric purposes, the major limitation currently being due to integration time and dead-time in frame acquisition.

Relative Biological Effectiveness (RBE) of (131)I Radiation Relative to (60)Co Gamma Rays.

OBJECTIVE: To assess relative biological effectiveness (RBE) of (131)I radiation relative to (60)Co gamma rays in glioblastoma spheroid cells. MATERIALS AND METHODS: : In this experimental study, glioblastoma spheroid cells were exposed to (131)I radiation and (60)Co gamma rays. Radiation induced DNA damage was evaluated by alkaline comet assay. Samples of spheroid cells were treated by radiation from (131)I for four different periods of time to find the dose-response equation. Spheroid cells were also exposed by 200 cGy of (60)Co gamma rays as reference radiation to induce DNA damage as endpoint. RESULTS: Resulted RBE of (131)I radiation relative to (60)Co gamma rays in 100 µm giloblastoma spheroid cells was equal to 1.16. CONCLUSION: The finding of this study suggests that (131)I photons and electrons can be more effective than (60)Co gamma rays to produce DNA damage in glioblastoma spheroid cells.

Evaluation of thyroid disorders during head-and-neck radiotherapy by using functional analysis and ultrasonography.

PURPOSE: To evaluate thyroid function and vascular changes during radiotherapy for patients with head and neck cancer. METHODS AND MATERIALS: Fifty patients treated with primary or postoperative radiotherapy for various cancers in the head and neck region were prospectively evaluated. The serum samples (triiodothyronine [T3], thyroxine [T4], thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]), the echo level of the thyroid gland, and color Doppler ultrasonography (CDU) parameters of the right inferior thyroid artery (RITA) of the patients were measured before and at regular intervals during radiotherapy. The thyroid gland dose-volume histograms of the patients were derived from their computed tomography-based treatment plans. RESULTS: There was a significant fall in TSH level (p < 0.0001) but an increase in FT4 (p < 0.0001) and T4 (p < 0.022) levels during the radiotherapy course. The threshold dose required to produce significant changes was 12 Gy (Biologically Effective Dose in 2-Gy fractions, BED(2)). There were significant rises in the patients' pulsatility index, resistive index, peak systolic velocity, blood volume flow levels, and RITA diameter (p < 0.0001), as detected by CDU during radiotherapy, compared to those parameters measured before the treatment. Hypoechogenicity and irregular echo patterns (p < 0.0001) were seen during radiotherapy compared to those before treatment. There was significant Pearson's correlation between the CDU parameters and T4, FT4, and TSH levels. CONCLUSIONS: Radiation-induced thyroiditis is regarded as primary damage to the thyroid gland. Thyroiditis can subsequently result in hypothyroidism or hyperthyroidism. Our results demonstrated that changes in thyroid vessels occur during radiotherapy delivered to patients. Vessel changes also can be attributed to the late effect of radiation on the thyroid gland. The hypoechogenicity and irregular echo patterns observed in patients may result from the increase in intrathyroidal flow.