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Background Over the last two decades, breast cancer remains the main cause of cancer deaths in women. To treat this type of cancer, radiation therapy (RT) has proved to be efficient. RT for breast cancer is, however, challenged by intrafractional motion caused by respiration. The problem is more severe for the left-sided breast cancer due to the proximity to the heart as an organ-at-risk. While particle therapy results in superior dose characteristics than conventional RT, due to the physics of particle interactions in the body, particle therapy is more sensitive to target motion. Conclusions This review highlights current and emerging strategies for the management of intrafractional target motion in breast cancer treatment with an emphasis on particle therapy, as a modern RT technique. There are major challenges associated with transferring real-time motion monitoring technologies from photon to particles beams. Surface imaging would be the dominant imaging modality for real-time intrafractional motion monitoring for breast cancer. The magnetic resonance imaging (MRI) guidance and ultra high dose rate (FLASH)-RT seem to be state-of-the-art approaches to deal with 4D RT for breast cancer.

INTRODUCTION: With an emphasis on the radioresistant nature of glioblastoma cells, the aim of the present study was to evaluate the radio-thermo-sensitizing effects of PCL-PEG-coated Superparamagnetic iron oxide nanoparticles (SPIONs) as a carrier of 5-iodo-2-deoxyuridine (IUdR) in monolayer culture of U87MG human glioma cell line. METHODS: Following monolayer culture of U87MG cells, nanoparticle uptake was assessed using Prussian blue staining and ICP-OES method. The U87MG cells were treated with an appropriate concentration of free IUdR and PCL-PEG-coated SPIONs (MNPs) loaded with IUdR (IUdR/MNPs) for 24 h, subjected to hyperthermia (water bath and alternating magnetic field (AMF)) at 43 °C, and exposed to X-ray (2 Gy, 6 MV). The combined effects of hyperthermia with or without magnetic nanoparticles on radiosensitivity of the U87MG cells were evaluated using colony formation assay (CFA) and Flowcytometry. RESULTS: Prussian blue staining and ICP-OES showed that the nanoparticles were able to enter the cells. The results also indicated that IUdR/MNPs combined with X-ray radiation and hyperthermia significantly decreased the colony formation ability of monolayer cells (1.11, 1.41 fold) and increased the percentage of apoptotic (2.47, 4.1 fold) and necrotic cells (12.28, 29.34 fold), when compared to IUdR combined with X-ray and hyperthermia or IUdR/MNPs + X-ray. MTT results revealed that the presence of IUdR/MNPs significantly increased the toxicity of AMF hyperthermia compared to the water bath method. CONCLUSIONS: Our study showed that SPIONs/PCL-PEG, as a carrier of IUdR, can enhance the cytotoxic effects of radiotherapy and hyperthermia and act as a radio-thermo-sensitizing agent. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00675-y.

Dose-escalated prostate radiotherapy (RT) can improve treatment outcomes, but rectal toxicity is the main limiting factor for introducing dose-escalated RT. Pushing rectal wall away from the prostate reduces the volume of the rectum in high-dose region, which can decrease both short- and long-term rectal toxicities after RT. This review focuses on the literature using different rectal displacement devices such as endorectal balloons, tissue spacers, rectal retractor, and ProSpare during prostate External beam radiotherapy, with regard to dosimetric effects, clinical benefits, prostate motion, and postoperative RT setting.

Radiomic features, clinical and dosimetric factors have the potential to predict radiation-induced toxicity. The aim of this study was to develop prediction models of radiotherapy-induced toxicities in prostate cancer patients based on computed tomography (CT) radiomics, clinical and dosimetric parameters. In this prospective study, prostate cancer patients were included, and radiotherapy-induced urinary and gastrointestinal (GI) toxicities were assessed by Common Terminology Criteria for adverse events. For each patient, clinical and dose volume parameters were obtained. Imaging features were extracted from pre-treatment rectal and bladder wall CT scan of patients. Stacking algorithm and elastic net penalized logistic regression were used in order to feature selection and prediction, simultaneously. The models were fitted by imaging (radiomics model) and clinical/dosimetric (clinical model) features alone and in combinations (clinical–radiomics model). Goodness of fit of the models and performance of classifications were assessed using Hosmer and Lemeshow test, − 2log (likelihood) and area under curve (AUC) of the receiver operator characteristic. Sixty-four prostate cancer patients were studied, and 33 and 52 patients developed ≥ grade 1 GI and urinary toxicities, respectively. In GI modeling, the AUC for clinical, radiomics and clinical–radiomics models was 0.66, 0.71 and 0.65, respectively. To predict urinary toxicity, the AUC for radiomics, clinical and clinical–radiomics models was 0.71, 0.67 and 0.77, respectively. We have shown that CT imaging features could predict radiation toxicities and combination of imaging and clinical/dosimetric features may enhance the predictive performance of radiotoxicity modeling.

Using a rectal retractor (RR) during salvage radiotherapy after radical prostatectomy is a promising approach for reducing dose to the rectum. The patient well tolerated the daily RR insertion. This area of research encourages researchers for a comprehensive evaluation of the role of the RR in postprostatectomy radiotherapy.

Here, the effects of combinatorial cancer therapy including radiotherapy (RT) and radiofrequency (RF) hyperthermia in the presence of gold-coated iron oxide nanoparticles (Au@IONPs), as a thermo-radio-sensitizer, are reported. The level of cell death and the ratio of Bax/Bcl2 genes, involved in the pathway of apoptosis, were measured to evaluate the synergistic effect of Au@IONPs-mediated RF hyperthermia and RT. MCF-7 human breast adenocarcinoma cells were treated with different concentrations of Au@IONPs. After incubation with NPs, the cells were exposed to RF waves (13.56 MHz; 100 W; 15 min). At the same time, thermometry was performed with an infrared (IR) camera. Then, the cells were exposed to 6 MV X-ray at various doses of 2 and 4 Gy. MTT (3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyltetrazolium bromide) assay was performed to evaluate cell viability and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression ratio of Bax/Bcl2. Cellular uptake of nanoparticles was confirmed qualitatively and quantitatively. The results obtained from MTT assay and qRT-PCR studies showed that NPs and RF hyperthermia had no significant effect when applied separately, while their combination had synergistic effects on cell viability percentage and the level of apoptosis induction. A synergistic effect was also observed when the cancer cells were treated with a combination of NPs, RF hyperthermia, and RT. On the basis of the obtained results, it may be concluded that the use of magneto-plasmonic NPs in the process of hyperthermia and RT of cancer holds a great promise to develop a new combinatorial cancer therapy strategy.

To investigate efficacy of a rectal retractor (RR) on rectal dose during image-guided dose-escalated prostate three-dimensional conformal radiotherapy (3DCRT). In all, 21 patients with localized prostate cancer were treated with a RR for 3DCRT in 40 × 2 Gy. Patient underwent two scans for radiotherapy planning, without and with RR. RR was used for the first half of the treatment sessions. Two plans were created for each patient to compare the effect of RR on rectal doses. PTW-31014 Pinpoint chamber embedded within RR was used for in vivo dosimetry in 6 of 21 patients. The patient tolerance and acute rectal toxicity were surveyed during radiotherapy using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Patients tolerated the RR well during 20 fractions with mild degree of anal irritation. Using a RR significantly reduced the rectal wall (RW), anterior RW and posterior RW dose–volume parameters. The average RW Dmean was 29.4 and 43.0 Gy for plans with and without RR, respectively. The mean discrepancy between the measured dose and planned dose was −3.8% (±4.9%). Grade 1 diarrhea, rectal urgency and proctitis occurred in 4, 2 and 3 cases, respectively. There were no grade ≥2 acute rectal toxicities during the treatment. Rectal retraction resulted in a significant reduction of rectal doses with a safe toxicity profile, which may reduce rectal toxicity. Dosimeter inserted into the RR providing a practical method for in vivo dosimetric verification. Further prospective clinical studies will be necessary to demonstrate the clinical advantage of RR.

Purpose This study was designed to assess the dose accumulation (DA) of bladder and rectum between brachytherapy fractions using hybrid-based deformable image registration (DIR) and compare it with the simple summation (SS) approach of GEC-ESTRO in cervical cancer patients. Material and methods Patients (n = 137) with cervical cancer treated with 3D conformal radiotherapy and three fractions of high-dose-rate brachytherapy were selected. CT images were acquired to delineate organs at risk and targets according to GEC-ESTRO recommendations. In order to determine the DA for the bladder and rectum, hybrid-based DIR was done for three different fractions of brachytherapy and the results were compared with the standard GEC-ESTRO method. Also, we performed a phantom study to calculate the uncertainty of the hybrid-based DIR algorithm for contour matching and dose mapping. Results The mean ± standard deviation (SD) of the Dice similarity coefficient (DICE), Jaccard, Hausdorff distance (HD) and mean distance to agreement (MDA) in the DIR process were 0.94 ±0.02, 0.89 ±0.03, 8.44 ±3.56 and 0.72 ±0.22 for bladder and 0.89 ±0.05, 0.80 ±0.07, 15.46 ±10.14 and 1.19 ±0.59 for rectum, respectively. The median (Q1, Q3; maximum) GyEQD2 differences of total D2cc between DIR-based and SS methods for the bladder and rectum were reduced by -1.53 (-0.86, -2.98; -9.17) and -1.38 (-0.80, -2.14; -7.11), respectively. The mean ± SD of DICE, Jaccard, HD, and MDA for contour matching were 0.98 ±0.008, 0.97 ±0.01, 2.00 ±0.70 and 0.20 ±0.04, respectively for large deformation. Maximum uncertainty of dose mapping was about 3.58%. Conclusions The hybrid-based DIR algorithm demonstrated low registration uncertainty for both contour matching and dose mapping. The DA difference between DIR-based and SS approaches was statistically significant for both bladder and rectum and hybrid-based DIR showed potential to assess DA between brachytherapy fractions.

Background: Radiation-induced rectal toxicities remain as a major risk during prostate radiotherapy. One approach to the reduction of rectal radiation dose is to physically increase the distance between the rectal wall and prostate. Therefore, the aim of this study was to evaluate whether the application of the rectal retractor (RR) can reduce rectal dose and toxicity in prostate cancer 3-dimensional conformal radiotherapy (3D-CRT). Methods: Overall, 36 patients with localized prostate cancer were randomized into the 2 groups, 18 patients with RR in-place and 18 without RR. All patients underwent planning computed tomography (CT). Patients were treated with 70 Gy in 35 fractions of 3D-CRT. In the RR group, RR was used during cone-down 20 treatment fractions. Acute and late gastrointestinal (GI) toxicities were assessed using EORTC/RTOG scoring system weekly during radiotherapy, 3, and 12 months after treatment. Device-related events were recorded according to CTCAE version 4.0. Patient characteristics, cancer differences, and dosimetric data for the RR and non-RR groups were compared using a Man-Whitney U test for continuous variables, and Fisher exact test for categorical data. The EORTC/RTOG scores for the 2 groups were compared using Fisher exact test. A P value

Background Intraoperative electron radiotherapy (IOERT) followed by hypofractionated whole breast irradiation (HWBI) provides the shortest possible time of adjuvant breast irradiation. The efficacy of either method has been described in previous reports; however, to our knowledge, the efficacy of combined therapy has not been reported. Aim To compare the toxicity and cosmetic outcome of IOERT as a tumor bed boost followed by HWBI with conventional whole breast irradiation (CWBI) followed by external electron tumor bed boost (EETBB) after breast conserving surgery (BCS) in patients with invasive breast cancer. Methods In 2019, a prospective noninferiority trial (IRCT20180919041070N2) was started. After BCS, early‐stage breast cancer patients were treated by IOERT (10 Gy) and HWBI (42.56 Gy in 16 fractions) or CWBI (50 Gy in 25 fraction) and EETBB (10 Gy in 5) in a double‐arm design. Acute/late toxicity and cosmetic outcome were evaluated by common toxicity criteria (CTC) after 1‐year follow‐up (FUP) at the level of p

Background. The standard treatment for breast cancer is breast-conserving surgery (BCS) with radiotherapy. If external beam radiation therapy (EBRT) can be safely replaced with intraoperative radiotherapy (IORT), it will help patients to save their breast and to have equivocal or better results in DFS and overall survival (OS). Methods. A total of 2022 patients with breast cancer treated during 6 years were enrolled in the current study. A total of 657, 376, and 989 patients received EBRT, radical, and boost dose by IORT, respectively, according to the IRIORT consensus protocol. The primary endpoint was recurrence and death. The secondary endpoint was the role of variables in recurrence and death. Results. With a mean follow-up of 34.5 and 40.18 months for the IORT and EBRT groups, respectively, there was a significant difference in DFS between electron boost and X-ray boost groups ( P = 0.037 ) and the electron radical group compared with EBRT ( P = 0.025 ), but there was no significant difference between other boost and radical groups in DFS and OS. Conclusions. IORT can be a preferred treatment modality because of its noninferior outcomes, and in some special conditions, it has superior outcomes compared to EBRT, particularly in delivering radical dose with IORT.

Background: Radiotherapy plays an essential role in breast cancer treatment following breast conserving surgery even in good-risk patients with ductal carcinoma in situ (DCIS) histology. It can be delivered by many techniques, among which is intraoperative radiotherapy (IORT). In recent years, intraoperative radiation therapy has had the same outcome compared with EBRT. Objectives: We studied whether whole breast radiotherapy (WBRT) could safely be replaced by IORT and its ability to control local recurrence like EBRT in pure DCIS. Methods: We assigned 138 patients into the external beam radiotherapy (EBRT), radical, and boost groups. The patients were treated during the last 6 years in the Cancer Research Center of Shahid Beheshti University of Medical Sciences. A total of 57 patients received EBRT, 45 patients received the radical dose of radiotherapy by IORT (36 patients received intraoperative electron radiotherapy [IOeRT] and 9 patients received intraoperative X-ray radiotherapy [IOxRT]) according to the IRIORT consensus protocol, and 36 patients received the boost dose of radiotherapy by IORT (15 patients received IOeRT and 21 patients received IOxRT). The IORT and EBRT groups were compared. The primary endpoint was local recurrence and death and the secondary endpoint was the role of variables in local recurrence. Results: With the mean follow-up of 37 months for the IORT group and 40.1 months for the EBRT group, local recurrence occurred in 8.8% (5 patients), 13.9% (5 patients), and 2.2% (1 patient) of the patients in the EBRT, boost, and radical groups, respectively. Concerning the local recurrence, no significant difference was observed between the radical and EBRT groups (P = 0.058) and between the boost and EBRT groups (P = 0.12). Hazard ratios (HRs) of grade, hormone receptor (HR), tumor size, and age in disease-free survival were evaluated and none of these variables had a significant role in local recurrence. Conclusions: IORT is a good alternative for WBRT in DCIS patients because of its non-inferiority results in comparison with EBRT. Being careful about age, tumor size, biological markers, and margin status is of high importance when using IORT for DCIS.

Aim: The purpose of this study was to assess and compare the incidence and severity of sensorineural hearing loss (SNHL) in head-and-neck patients undergoing radiotherapy (RT) and concurrent cisplatin-based chemoradiotherapy (CRT). Materials and Methods: Pure tone audiometry (PTA) was performed at 0.25–12 kHz on 35 RT and 25 CRT patients after 12-month followed up. The hearing loss was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria. Results: SNHL increased to 84% in patients who had received CRT, compared with 26% increasing in patients who had treated with RT. There was an increased risk of SNHL at all frequencies for ears received a cochlear mean dose >50 Gy in RT group, compared to those receiving cochlear mean dose >30 Gy in CRT group. SNHL was more severe at higher frequencies in both patient groups. Conclusion: Characteristic of radiation-induced SNHL is different from CRT-induced SNHL, especially in threshold radiation dose and PTA frequency.

The aim of this study was the evaluation of induced DNA damages of human prostate cancer cells, DU-145, treated with a combination of radiofrequency capacitive hyperthermia (HT) and teletherapy (EBRT) compared to a combination of teletherapy with high-dose rate brachytherapy (BR).DU-145 cells were cultured as spheroids in 300 micron diameter. Then the following treatments were conducted: (a) EBRT at doses of either 2 Gy or 4 Gy of photon 15 MV, (b) HT for 0, 30, 60, and 90 minutes duration at 43 °C from a 13.56 MHz radiofrequency capacitive heating device (Celsius TCS), (c) BR with Ir-192 seed at doses of either 2 Gy or 5.5 Gy, (d) The mentioned HT followed by EBRT (HT + EBRT) and (e) EBRT followed by BR (EBRT + BR). Alkaline comet assay was performed to measure tail moment.The induced DNA damages of DU-145 cells treated by adding HT to EBRT compared with EBRT alone, showed a significant enhancement; 3.28 and 5.14 times respectively for 30 and 60 minutes HT. By plotting dose-response curves, we could find a range of doses, which create radiobiological iso-effect in HT + EBRT and EBRT + BR treatments.This study suggests that about DNA damages of DU-145 cells, HT + EBRT could partly be considered as an alternative to EBRT + BR.

Glioblastoma multiform (GBM) is the most prevalent and aggressive type of primary brain tumor. None of the current conventional treatment methods has improved treatment considerably. Therefore, in this study the effect of magnetic nanoparticles coated with poly (caprolactone)-poly (ethylene glycol) (PCL-PEG) as a 5-iodo 2'deoxyuridine (IUdR) carrier in the presence of hyperthermia and 6 MV (megavoltage) X-ray radiation, were investigated in a spheroid model of U87MG glioblastoma cell line using colony formation assay.First, the human glioblastoma cell line U87MG was cultured as a spheroid using the liquid overlay technique. Spheroids on day 10 with 100 mm diameters were treated with 1 µM IUdR or nanoparticles as IUdR carriers for one volume doubling time (VDT) of spheroids (67 h) and hyperthermia at 43 °C for 1 h, and then irradiated with 2 Gy of 6 MV X-ray in different groups. Finally, the effect of treatment on colony-forming ability was obtained by colony formation and alkaline assay.Our results revealed that hyperthermia in combination with radiation could significantly reduce the colony number of glioblastoma spheroid cells treated with IUdR or nanoparticles as IUdR carriers. However, the extent of reduction in colony number following treatment with IUdR-loaded nanoparticles in combination with hyperthermia and then X-ray radiation was significantly more than free IUdR.According to this study, PCL-PEG-coated magnetic nanoparticles are effective delivery vehicles for IUdR into cells. Moreover, they can act as a radiosensitizer and thermosensitizer in the treatment of the glioblastoma cell line.

Glioma is one of the most common malignant cancers of the central nervous system (CNS). Radiatherapy and chemotherapy may be used to slow the growth of tumors that cannot be removed with surgery. The current study developed a combination therapy tool using Nanographene oxide (NGO) functionalized with poly lactic-co-glycolic acid (PLGA) as a carrier of 5-iodo-2-deoxyuridine (IUdR) for glioma cancer treatment. U87MG cells were treated in different groups with IUdR, PLGA-coated Nanographene oxide (PLGA-NGO), IUdR-loaded PLGA-coated Nanographene oxide (IUdR-PLGA-NGO), 2 Gy 6 MV X-ray radiation, and near-infrared region (NIR) laser radiation. PLGA-NGO showed excellent biocompatibility, high storage capacity for IUdR and high photothermal conversion efficiency. It was effectively employed to create cell damage in the U87MG cell line in the presence of X-ray (6 MV) and NIR laser. Moreover, IUdR-PLGA-NGO + X-ray + NIR laser significantly reduced the plating efficiency of the cells in comparison with IUdR-PLGA-NGO + X-ray and IUdR-PLGA-NGO + NIR laser. Furthermore, Prussian blue staining showed that IUdR-PLGA-NGO-SPIONs were delivered into glioblastoma cells. The PLGA-NGO loaded with IUdR under NIR and X-ray radiation exhibited the highest cytotoxicity toward U87MG cells when compared with other treatment methods, indicating efficient radio-photothermal targeted therapy.

Objectives Immediately or after head-and-neck (H&N) cancer chemoradiotherapy (CRT), patients may undergone significant sensorineural hearing loss (SNHL) which could affect their quality of life. Radiomic feature analysis is proposed to predict SNHL induced by CRT. Material and methods 490 image features of 94 cochlea from 47 patients treated with three dimensional conformal RT (3DCRT) for different H&N cancers were extracted from CT images. Different machine learning (ML) algorithms and also least absolute shrinkage and selection operator (LASSO) penalized logistic regression were implemented on radiomic features for feature selection, classification and prediction. Also, LASSO penalized logistic model was used for outcome modelling. Results The predictive power of ten ML methods was more than 70% (in accuracy, precision and area under the curve of receiver operating characteristic curve (AUC)). According to the LASSO penalized logistic modelling, 10 of the 490 radiomic features selected as the associated features with SNHL status. All of the 10 features were statistically associated with SNHL (all of adjusted P-values Conclusion CT radiomic analysis proposed in this study, could help in the prediction of hearing loss induced by chemoradiation. Our study also, demonstrates that combination of radiomic features with clinical and dosimetric variables can model radiotherapy outcome such as SNHL.

The present study aims to calculate the received dose by lungs and heart, as organs at risk (OAR), during intraoperative electron radiotherapy (IOERT) of left breast cancer at the presence and absence of shielding disk using Monte Carlo (MC) simulation. LIAC 12, a dedicated IOERT Linac, and an anthropomorphic phantom were considered in this study to simulate particle tracks of 6, 8, 10, and 12 MeV nominal electron energies using EGSnrc MC particle transport simulation code. The results showed that for increasing electron beam energies in the absence of shielding disk, left lung and heart dose would also be increasing so that, maximum left lung and heart dose respectively increases from 0.512 to 9.920 Gy and from 0 to 0.506 Gy with increment of electron energy from 6 to 12 MeV. Employing the shielding disk in 6 and 8 MeV energy can reduce the heart and left lung maximum dose to zero. On the other hand, this dose reduction at 10 and 12 MeV energy was respectively about 99% and 93.5% for heart and 99.9% and 92.9% for left lung. Right lung did not receive a remarkable dose both in presence and absence of shielding disk. From the results, it can be concluded that employing the shielding disk can effectively reduce the received dose to OARs.

Background and Objective: Prostate cancer is the second cause of death in men worldwide. In this study, the cytotoxic effects of PLGA polymer-coated gold Magnetic Nanoparticles (MGNPs), as a novel treatment to enhance radiation and thermal sensitivity in the presence of hyperthermia (43°C) and electron beam, on DU145 prostate cancer cells were investigated. Methods: Nanoparticles were characterized using TEM, DLS, XRD and SAED methods. MGNPs entrance into the cells was determined using Prussian blue staining and TEM. Furthermore, the cytotoxic effects of combinatorial treatment modalities were assessed by applying colony and sphere formation assay. Results: Our results revealed that the decrease of colony and sphere numbers after combinatorial treatment of hyperthermia and radiation in the presence of nanoparticles was significantly higher than the other treatment groups (P Conclusion: According to the study, magnetic gold nanoparticles, in addition to having a high atomic number, can effectively transmit heat produced inside them to the adjacent regions under hyperthermia, which increases the effects of radio-thermosensitivity, respectively.

Background and Purpose: As a feasible approach, radiotherapy has a great role in prostate cancer (Pca) management. However, Pca patients have an increased risk of femoral head damages including fractures after radiotherapy. The mechanisms of these complications are unknown and time of manifestations is too long; however, they may be predicted by early imaging. The main purpose of this study was to assess the early changes in femoral heads in Pca patients treated with intensity-modulated radiation therapy (IMRT) using multiparametric magnetic resonance imaging (mpMRI) radiomic feature analysis. Materials and Methods: Thirty Pca patients treated with IMRT were included in the study. All patients underwent two mpMRI pre- and postradiotherapy. Thirty-four robust radiomic features were extracted from T1, T2, and apparent diffusion coefficient (ADC) obtained from diffusion-weighted images. Wilcoxon signed-rank test was performed to assess the significance of the change in the mean T1, T2, and ADC radiomic features postradiotherapy relative to preradiotherapy values. The percentage change values were normalized based on the natural logarithm base ten. Features were also ranked based on their median changes. Results: Sixty femoral heads were analyzed. All radiomic features have undergone changes. Significant postradiotherapy radiomic feature changes were observed in 20 and 5 T1- and T2-weighted radiomic features, respectively (P < 0.05). ADC features did not vary significantly postradiotherapy. The mean radiation dose received by femoral heads was 40 Gy. No fractures were observed within the follow-up time. Different features were found as high ranked among T1, T2, and ADC images. Conclusion: Early structural change analysis using radiomic features may contribute to predict postradiotherapy fracture in Pca patients. These features can be identified as being potentially important imaging biomarkers for predicting radiotherapy-induced femoral changes.

Background: Breast conserving surgery (BCS) and its following radiotherapy is an accepted therapeutic method for patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). Objectives: The aim of this study was to investigate the effect of intraoperative electron radiotherapy on women with breast cancer (invasive lobular and ductal carcinoma). Methods: Between August 2013 and September 2017, 968 patients, who were referred to Cancer Research Center, Shahid Beheshti University of Medical Sciences with invasive breast cancer, were treated with breast-conserving surgery and radiotherapy. Of those, 426 patients received a tumor bed boost with intraoperative electron radiotherapy (IOERT) during lumpectomy (58 patients with pure invasive lobular carcinoma, 239 patients with pure invasive ductal carcinoma, and 129 patients with other diagnoses). 542 patients received a tumor bed boost with conventional external beam radiotherapy post lumpectomy (24 patients with pure invasive lobular carcinoma, 418 patients with pure invasive ductal carcinoma, and 100 patients with other diagnoses). The patients were followed up to 49 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. We retrospectively analyzed outcomes of breast cancer treated with boost intraoperative electron radiotherapy (pure ILC and IDC groups) and in other group treated with boost conventional external beam radiotherapy (pure ILC group). Results: None of the ILC patients had recurrence in the two groups. The four-year survival rate for ILC patients was 100%, but in the IDC group the survival rate was 97%. Survival analyses showed patients with IDC had a higher risk of ipsilateral breast tumor recurrence (IBTR) and metastasis. Conclusions: Overall, the rates of IBTR and metastasis in the ILC boost IOERT group were significantly low. This finding suggests that IOERT technique deployment in ILC had no inferiority compared with the control group.

Purpose: The objective of the study was to evaluate the effectiveness of a rectal retractor (RR) designed to protect rectal tissue in intensity-modulated radiotherapy (IMRT) by pushing rectal wall (RW) away from the prostate. Materials and Methods: Twelve patients with localized prostate cancer were enrolled into this study. Patients underwent two computed tomography (CT) scans without and with RR. A prescription of 80 Gy in 40 fractions was planned on CT scans with and without RR. This study evaluates the ability of the RR in RW dose reduction, in particular reduction of the RW V70Gy≥ 25% in comparison with the plan without RR dose-volume histograms were generated with and without RR. The patient's tolerance was assessed by patient-reported outcomes. Results: The planning target volume coverage was equal for both without and with RR (P = 0.155). The mean dose to the RW was statistically significantly lower for the plan with RR than that for the plan without RR, a mean reduction of 5.8 Gy (P = 0.003). Significant relative reductions in rectal dose-volume parameters whether in absolute volume (cc) or as a percentage of contoured RW were detected. A relative reduction more than 25% in RW V70Gy(%) in 100% of patients was achieved. The rectal retraction resulted in a significant increase in the prostate to the rectum space at the prostate midgland level, an absolute increase of 2.7 mm. The retraction of the rectum induced a mean (±standard deviation) pain score of 2.7 (±1.3) according to the visual analog score. Conclusion: The application of a RR showed a remarkable rectal sparing effect during prostate IMRT. This may lead to reduced acute and late rectal toxicities in prostate IMRT.

BackgroundIntraoperative radiotherapy is a method of choice to deliver a critical radiation dose to the tumour bed immediately after surgical excision.AimThe purpose of this work is to check the dose delivered to the patients during intraoperative electron beam radiation therapy (IOERT) in the conservative treatment of breast cancer, by means of reference dose measurement using radiochromic (EBT-2) films.Material and methodsNinety patients with early-stage breast cancer underwent exclusive IOERT to the tumour bed using a LIAC linear accelerator. Absolute dose measurements were done with film pieces. After irradiation, the pixel values of the films were obtained via MATLAB and ImageJ softwares. Calibration curve was also used for calculating net optical density. Expected dose was compared to the patient delivered dose.ResultsThe mean deviation of the delivered dose from the expected one was 2·56% that is well in the accepted criteria. Only in one case, there was a larger deviation due to barometer miscalibration.FindingsEBT-2 film response is independent from dose-per-pulse and as it was shown in this study it can be robustly used during breast IOERT for dosimetric and also positioning verifications.

Introduction Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in humans. Current conventional treatment could not effectively increase the survival rate of patients who suffered from GBM. In clinical view, some experiments which can mimic in vivo conditions to evaluate anticancer agent effects on tumors are very useful. We can fairly reach to this goal using 3-dimentional spheroids rather than monolayer culture. The aim of this study was to determine the cytotoxicity caused by Navelbine, hyperthermia and radiation on glioma spheroids. Methods The spheroid cells were separately or simultaneously treated with the doses of 7.5 μg/ml Navelbine for 50.3 h, irradiated with 2 Gy and incubated at 43 °C for 1 h. Comet and colony formation assays were applied to assess the DNA damages and survival rate of the cells. Results In both comet and colony formation assays, cell damage in all treated groups was significantly higher in comparison with control group ( P 0.05). Moreover, the synergistic effect of combined groups such as: hyperthermia and radiotherapy, Navelbine and radiotherapy and combination of Navelbine-hyperthermia-radiotherapy was observed. Conclusions Combined agents with low concentration can cause a synergistic effect on treatment procedure and increased damages in multicellular spheroids.

5-iodo-2-deoxyuridine (IUdR) has been demonstrated to induce an appreciable radiosensitizing effect on glioblastoma patients, but due to the short circulation half-life times and failure to pass through the blood-brain barrier (BBB), its clinical use is limited. Accordingly, in this study, we used magnetic graphene oxide (NGO/SPIONs) nanoparticles coated with PLGA polymer as a dynamic nanocarrier for IUdR and, evaluated its sensitizing enhancement ratio in combination with a single dose X-ray at clinically megavoltage energies for treatment of C6 glioma rats. Nanoparticles were characterized using Zetasizer and TEM microscopy, and in vitro biocompatibility of nanoparticles was assessed with MTT assay. IUdR/MNPs were intravenously administered under a magnetic field (1.3 T) on day 13 after the implantation of C6 cells. After a day following the injection, rats exposed with radiation (8 Gy). ICP-OES analysis data indicated an effective magnetic targeting, leading to remarkably improved penetration through the BBB. In vivo release analysis with HPLC indicated sustained release of IUdR and, prolonged the lifespan in plasma (P .01). In addition, our findings revealed a synergistic effect for IUdR/MNPs coupled with radiation, which significantly inhibited the tumor expansion (100%), prolonged the survival time (100%) and suppressed the anti-apoptotic response of glioma rats by increasing Bax/Bcl-2 ratio (2.13-fold) in compared with the radiation-only. In conclusion, besides high accumulation in targeted tumor sites, the newly developed IUdR/MNPs, also exhibited the ability of IUdR/MNPs to significantly enhance radiosensitizing effect, improve therapeutic efficacy and increase toxicity for glioma-bearing rats.

Conventional cancer treatment methods suffer from many limitations such as non-specificity in discrimination between healthy and malignant cells. The aim of this study was to investigate the role of polymeric gold-photoactive nanoparticles (PGPNPs) conjugated with folic acid (FA) as theranostic nanoparticles for active targeting, real-time fluorescence tracing and radiosensitivity inducition in LNCaP prostate cancer cells.The cellular uptake and cytotoxicity effect of gold nanoparticles (PGPNPs and PGPNPs-FA) after 2 and 24 h treatment were evaluated in in both cancer (LNCaP) and normal (HUVEC) cells using fluorescent microscopy, Induced coupled plasma optical emission spectrometry (ICP-OES) and Tetrazolium bromide dye (MTT), respectively. The therapeutic efficacy was analyzed on the LNCaP cells. For this purpose, LNCaP cells were treated by nanoparticles and ionizing radiation, and the synergistic effect of treatment methods were evaluated by colony formation assay (CFA) and Flow cytometry analysis.The results of fluorescence imaging and ICP-OES data showed that the LNCaP cells absorbed PGPNP-FA nanoparticles more than PGPNP (P 0.001). Also, the uptake of nanoparticles was significantly greater in cancer cells than in healthy ones (P 0.01). MTT assay results indicated higher cytotoxic effect of nanoparticles conjugated with FA in folate-receptor overexpressing LNCaP cancer cells compared to HUVEC normal cells (P 0.01). Furthermore, CFA and Flow cytometry results demonstrated that combinatorial therapy of polymeric gold nanoparticles with/without FA and ionizing radiation at various doses (2, 4 and 6 Gy) had a synergistic effect on survival fraction and induction of apoptotic and necrotizing cell death (P 0.01).PGPNPs-FA nanoparticles led to higher and more specific uptake and accumulation of nanoparticles in LNCaP cells, thereby increasing the ability of gold nanoparticles as radio-sensitizer.

Single fraction nature of intraoperative radiotherapy highly demands a quality assurance procedure to qualify both beam setup and treatment delivery. The aim of this study is to evaluate the treatment setup during breast intraoperative electron radiotherapy (IOERT) and in-vivo dose delivery verification.Twenty-five breast cancer patients were enrolled and setup verification for each case was performed using C-arm imaging. The received dose by surface and distal end of target was measured by EBT2 film. The significance level of difference between obtained dosimetry results and predicted ones was evaluated by the T statistical test.Acquired C-arm images in two different oblique views revealed any misalignment between the applicator and shielding disk. The mean difference between the measured surface dose and expected one was 1.8% ± 1.2 (p = 0.983) while a great disagreement, 11.1% ± 1.5 (p 0.001), was observed between the measured distal end dose and expected one. This discrepancy is mainly correlated to the backscattering effect from the shielding disk. Target depth nonuniformities can also contribute to this remarkable difference.Employing the intraoperative imaging for IOERT setup verification can considerably improve the treatment quality. Therefore, it is suggested to implement this imaging procedure as a part of treatment quality assurance. Favorable agreement between the predicted and measured surface doses demonstrates the applicability of EBT2 film for dose delivery verification. The results of in-vivo dosimetry showed that the electron backscattering from employed shielding disk can affect the received dose by the distal end of tumor bed.

Background The main purpose of this study was to assess the structural changes in the bladder wall of prostate cancer patients treated with intensity-modulated radiation therapy using magnetic resonance imaging texture features analysis and to correlate image texture changes with radiation dose and urinary toxicity. Methods Ethical clearance was granted to enroll 33 patients into this study who were treated with intensity-modulated radiation therapy for prostate cancer. All patients underwent two magnetic resonance imagings before and after radiation therapy (RT). A total of 274 radiomic features were extracted from MR-T2W–weighted images. Wilcoxon singed rank-test was performed to assess significance of the change in mean radiomic features post-RT relative to pre-RT values. The relationship between radiation dose and feature changes was assessed and depicted. Cystitis was recorded as urinary toxicity. Area under receiver operating characteristic curve of a logistic regression–based classifier was used to find correlation between radiomic features with significant changes and radiation toxicity. Results Thirty-three bladder walls were analyzed, with 11 patients developing grade ≥2 urinary toxicity. We showed that radiomic features may predict radiation toxicity and features including S5.0SumVarnc, S2.2SumVarnc, S1.0AngScMom, S0.4SumAverg, and S5. _5InvDfMom with area under receiver operating characteristic curve 0.75, 0.69, 0.65, 0.63, and 0.62 had highest correlation with toxicity, respectively. The results showed that most of the radiomic features were changed with radiation dose. Conclusion Feature changes have a good correlation with radiation dose and radiation-induced urinary toxicity. These radiomic features can be identified as being potentially important imaging biomarkers and also assessing mechanisms of radiation-induced bladder injuries.

Background: Transfusion-associated graft-versus-host disease is a complication being mortal in 90% of cases. Today, Co-60 devices are utilized for the suppression of the lymphocytes to prevent this complication. Due to problems such as radioactive source age, problems in source replacement, and protection risks, we sought to replace a linear accelerator for this purpose and carefully determinate the X-ray dose and other settings. Methods: First, the venous blood of the right-handed people with blood group O+ was exposed to different radiation doses of Linac and diluted. The proliferative responses of the exposed cells were examined by MTT assay and TB in comparison with controls after 48h. The average percentage of cell survival at each delivered dose and the required dose of radiation for the inhibition of lymphocyte proliferation were checked and the optimal dose of radiation was obtained as 25 Gy in a special radiation condition. Results: The results indicated that the irradiation with 25 Gy at 3.5 Gy/min in the internal mid-plan by compact 6MV for 30*30-field size at an 8 cm-distance of the samples to the source and 1370-monitor unit could completely suppress the lymphocytes. Under the same condition and 1096-monitor unit for total 20 Gy, we did not find optimal results. Conclusions: In this research, we found that a linear accelerator in a specific exposure condition is a suitable alternative for Cobalt-60 sources and the above-mentioned condition of irradiation can be used to overcome the GVHD concern.

The aim of this study was to generate the dose-response curves by six normal tissue complication probability (NTCP) models and ranking the models for prediction of radiation induced sensorineural hearing loss (SNHL) caused by head and neck radiation therapy (RT).Pure tone audiometry (PTA) was performed on 70 ears of patients for 12 months after the completion of RT. The SNHL was defined as a threshold shift ≤15 dB at two contiguous frequencies according to the common toxicity criteria for adverse events scoring system. The models evaluated were: Lyman and Logit; Mean Dose; relative seriality (RS); Individual critical volume (CV); and population CV models. Maximum likelihood analysis was used to fit the models to experimental data. The appropriateness of the fit was determined by the two-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion.The dose of 50% complication rate (DCochlea shows a different behavior against different NTCP models; it may be due to its small size.

Many combined therapies have been proposed to enhance radiotherapy outcome, but they have several limitations. As a new feasible strategy, combination of radiotherapy with bacteria showed a significant positive impact on the tumor treatment and metastasis inhibition. Although probiotic bacteria and radiotherapy alone can be effective in the treatment of different cancers, the combination of these two therapies seems to enhance therapeutic outcome and is cost-effective. Bacterial cells can act as therapeutic/gene/drug delivery vehicles as well as theranostic agents. In this communication, we reviewed current evidences, studies, suggestions, and future-based directions on combination of radiotherapy and bacteria. In another sections, an overview on tumor hypoxia, bacteria in cancer therapy, and combination of radiotherapy and bacteria is presented. A brief overview on trials and animal studies which used bacteria to protect normal tissues against radiotherapy-induced complications is also included.

The aim of this study was to investigate the effect of hyperthermia, 6 MeV electron radiation and combination of these treatments on cancer cell line DU145 in both monolayer culture and spheroids enriched for prostate cancer stem cells (CSCs). Flowcytometric analysis of the expression of molecular markers CD133+/CD44+ was carried out to determine the prostate CSCs in cell line DU145 grown as spheroids in serum-free medium. Following monolayer and spheroid culture, DU145 cells were treated with different doses of hyperthermia, electron beam and combination of them. The survival and self-renewing of the cells were evaluated by colony formation assay (CFA) and spheroid formation assay (SFA). Flowcytometry results indicated that the percentage of CD133+/CD44+ cells in spheroid culture was 13.9-fold higher than in the monolayer culture. The SFA showed significant difference between monolayer and spheroid culture for radiation treatment (6 Gy) and hyperthermia (60 and 90 min). The CFA showed significantly enhanced radiosensitivity in DU145 cells grown as monolayer as compared to spheroids, but no effect of hyperthermia. In contrast, for the combination of radiation and hyperthermia the results of CFA and SFA showed a reduced survival fraction in both cultures, with larger effects in monolayer than in spheroid culture. Thus, hyperthermia may be a promising approach in prostate cancer treatment that enhances the cytotoxic effect of electron radiation. Furthermore, determination and characterization of radioresistance and thermoresistance of CSCs in the prostate tumor is the key to develop more efficient therapeutic strategies.

PURPOSE Rectal toxicity is one of the most common side effects in prostate cancer radiotherapy. Prediction of such effect is of particularly interest to personalize the treatment. This study's purpose is to investigate the performance of predictive radiomic models developed based on clinical, dosimetric parameters and radiomic features extracted from rectal wall magnetic resonance image (MRI). METHODS This prospective study was conducted on 33 pathologically proven prostate cancer patients treated with intensity modulated radiation therapy (IMRT). Patient's clinical and dosimetric parameters were collected and rectal toxicity was assessed by common terminology criteria for adverse events (CTCAE). All patients underwent two MRI scans before and after IMRT course with same imaging protocol. A wide range of radiomic texture features were extracted from rectal wall MR images including T2 weighted (T2W) and apparent diffusion coefficient (ADC) scans (pre and post-IMRT) and robust features were found. Lasso regularization was used to create multivariable Elastic Net logistic regression model, based on the clinical, dosimetric and robust features for prediction and feature selection, simultaneously. All models were cross-validated using repeated 5-fold cross-validation and their performance were evaluated by area under the curve of the ROC curve (AUC), sensitivity and specificity. RESULTS Thirty-three patients were evaluated and eighteen patients were developed grade ≥ 1 rectal toxicity. From each ROI, 270 radiomic features were extracted and 37 radiomic features (14%) were found robust against delineations. Different clinical, dosimetric and imaging features were regularized and selected by Elastic Net. Thirteen predictive models including one clinical, two radiomics and eight integrated clinical-radiomic models were built. The predictive performance (AUC) for T2 and ADC-radiomic models were 0.636 and 0.788 respectively. We observed that the combination of T2 and ADC image features with clinical and dosimetric data have led to higher performance and T2-clinical-radiomic model had higher performance (AUC 0.933, Sensitivity 0.941 & Specificity 0.923) rather than ADC-clinical radiomics model (AUC 0.90, Sensitivity 0.941 & Specificity 0.846). Post, delta and total radiomic-clinical models also had good predictive performance. CONCLUSIONS Rectal wall MR radiomic features integrating with clinical and dose-volume parameters could improve the prediction performance of radiotherapy induced proctitis. The authors have demonstrated the performance of radiomic features extracted from pre IMRT T2W and ADC MR Images for prediction of IMRT induced rectal toxicity. These results may be used to tailor the therapy in terms of patient and treatment approach selection. Post-IMRT models also, may be used as hypothetical issues for predicting late rectal injuries.

The aim of this study was to investigate the risk of sensorineural hearing loss (SNHL) and the relationship between SNHL and radiation dose to the cochlea and frequency range of hearing loss in patients with head and neck cancer. Pure tone audiometry at 250–12,000 Hz was performed on 29 patients diagnosed with head and neck tumours who were treated with 3-dimensional conformal radiation therapy and followed up for 6 months. Paired t test indicated that the mean air conduction threshold before and after radiotherapy was significantly different (paired t test, p

Goals: IORT is an accepted standard treatment for early stages of breast cancer in selected cases. This is proven in two large trials: ELIOTandTARGIT-AbasedonelectronhighvoltagebeamandlowkV X-ray energy respectively. Methods: Published results of the two trials aimed to evaluating local recurrence as the final outcome. In this study these results were compared with each other. Results: In the ELIOT study the local recurrence rate is 4/4% versus 0.4% in patients who received IORT and EBRT, in comparison to 3.2% and 1.3% in the TARGIT-A trial; these differences needs to be under more consideration regarding the efficacy and beneficenceofIORT.Herebywearegoingtoanalyzethedataofthese two trials to confirm the strategy of IORT in breast cancer as boost or radical modalities. Patient selection according to classification of ASTRO or ESTRO guidelines confirmed the local recurrence rate of IOERT (ELIOT) in low risk patients similar to TARGIT decrease to less than 1.9%. Conclusion: Statistical analysis revealed that in patients of both trials with matching clinical, pathological and biological profile for both methods, the radical IORT using electron and low kV X-ray are effective and acceptable. It seems in patients with low risk factors, IORT is more effective than EBRT. We compared ELIOT and TARGIT-A trial documents and found all of similarity and difference and referred to these two trials recommending using IORT for selected cases of breast cancer with at least non inferiority in DFS, OS, with superiority in cosmetic, non breast death and more.