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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.

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.

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

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.

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.

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 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 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.

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:Currently, the potential application of gold nanoparticles (AuNPs) to increase the efficiency of radiation therapy has been widely investigated. However, lack of an appropriate method to estimate the dose distribution in a nanoparticle-laden tissue limits the applicability of nanoparticles in radiotherapy clinics. Polymer gel dosimetry provides an accurate and precise system that facilitates the measurement of dose distribution in full three dimensions.Objective: In this study, the effect of radiation dose enhancement of AuNPs was assessed through gel dosimetry analysis.Material and Methods: For this purpose, AuNPs were integrated in MAGIC_f polymer gel dosimeter and irradiated by 6 Mv X-ray beam. The irradiated gel was then evaluated through two modalities of magnetic resonance imaging (MRI) and optical computed tomography (OCT).Result: MRI and OCT scanning of MAGIC_f gels containing 0.1 mM AuNPs demonstrated dose enhancements of 7.8% and 6.8%, respectively.Conclusion: Polymer gel dosimetry has the potential to provide a new platform for the investigation and optimization of the applicability of nanoparticles in radiation therapy.

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.

Aim Verification of dose distributions for gynecological (GYN) brachytherapy implants using EBT Gafchromic film. Background One major challenge in brachytherapy is to verify the accuracy of dose distributions calculated by a treatment planning system. Materials and methods A new phantom was designed and fabricated using 90 slabs of 18 cm × 16 cm × 0.2 cm Perspex to accommodate a tandem and Ovoid assembly, which is normally used for GYN brachytherapy treatment. This phantom design allows the use of EBT Gafchromic films for dosimetric verification of GYN implants with a cobalt-60 HDR system or a LDR Cs-137 system. Gafchromic films were exposed using a plan that was designed to deliver 1.5 Gy of dose to 0.5 cm distance from the lateral surface of ovoids from a pair of ovoid assembly that was used for treatment vaginal cuff. For a quantitative analysis of the results for both LDR and HDR systems, the measured dose values at several points of interests were compared with the calculated data from a commercially available treatment planning system. This planning system was utilizing the TG-43 formalism and parameters for calculation of dose distributions around a brachytherapy implant. Results The results of these investigations indicated that the differences between the calculated and measured data at different points were ranging from 2.4% to 3.8% for the LDR Cs-137 and HDR Co-60 systems, respectively. Conclusion The EBT Gafchromic films combined with the newly designed phantom could be utilized for verification of the dose distributions around different GYN implants treated with either LDR or HDR brachytherapy procedures.

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.

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.

Cancer stem cells (CSCs) have been identified as the main center of tumor therapeutic resistance. They are highly resistant against current cancer therapy approaches particularly radiation therapy (RT). Recently, a wide spectrum of physical methods has been proposed to treat CSCs, including high energetic particles, hyperthermia (HT), nanoparticles (NPs) and combination of these approaches. In this review article, the importance and benefits of the physical CSCs therapy methods such as nanomaterial-based heat treatments and particle therapy will be highlighted.

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.

Purpose Intraoperative radiation therapy (IORT) using electron beam is commonly done by mobile dedicated linacs that have a variable range of electron energies. This paper focuses on the evaluation of the EBT2 film response in the green and red colour channels for IORT quality assurance (QA). Methods The calibration of the EBT2 films was done in two ranges; 0–8 Gy for machine QA by red channel and 8–24 Gy for patient-specific QA by green channel analysis. Irradiation of calibration films and relative dosimetries were performed in a water phantom. To evaluate the accuracy of the film response in relative dosimetry, gamma analysis was used to compare the results of the Monte Carlo simulation and ionometric dosimetry. Ten patients with early stage breast cancer were selected for in-vivo dosimetry using the green channel of the EBT2 film. Results The calibration curves were obtained by linear fitting of the green channel and a third-order polynomial function in the red channel (R2 = 0.99). The total dose uncertainty was up to 4.2% and 4.7% for the red and green channels, respectively. There was a good agreement between the relative dosimetries of films by the red channel, Monte Carlo simulations and ionometric values. The mean dose difference of the in-vivo dosimetry by green channel of this film and the expected values was about 1.98% ± 0.75. Conclusion The results of this study showed that EBT2 film can be considered as an appropriate tool for machine and patient-specific QA in IORT.

Background Cervical cancer brachytherapy has an effective role on the tumor control probability as a boost and/or single treatment option. High-dose-rate 60 Co brachytherapy units are used in many radiation oncology centers in Iran. Rectum and bladder tissues are considered as organs at risk in radiation treatment of cervical cancers, and they should be spared from unwanted radiation risk. Purpose In the present study, the effect of additional tungsten shield was investigated in a new colpostat design for bladder protection against radiation. Methods and Materials Monte Carlo (MC) simulation has been performed using the MC N-Particle eXtended version 2.4.0 transport code. The HDR GZP6 brachytherapy source applicator was simulated along with its colpostats. The f6 tally was used for absorbed dose calculation; and for model validation, we used from dosimetric features of the GZP6 treatment planning system. Results Results calculated by MC simulation method showed that dose reduction at the end of the colpostat was 2.44% for the medium colpostat and a dose increase of 1.35% was obtained for the small colpostat. In the reference point of the bladder (at the distance 1 cm from the end point of the colpostat), the percentages of dose reductions were also 25% and 15% for medium and small colpostats, respectively. Conclusions Results show that the absorbed dose in the bladder tissue can be reduced significantly using a shielded colpostat.

Purpose: The aim of this study was to evaluate and analytically compare different calculation algorithms applied in our country radiotherapy centers base on the methodology developed by IAEA for treatment planning systems (TPS) commissioning (IAEA TEC‐DOC 1583). Material & Methods: Thorax anthropomorphic phantom (002LFC CIRS inc.), was used to measure 7 tests that simulate the whole chain of external beam TPS. The dose were measured with ion chambers and the deviation between measured and TPS calculated dose was reported. This methodology, which employs the same phantom and the same setup test cases, was tested in 4 different hospitals which were using 5 different algorithms/ inhomogeneity correction methods implemented in different TPS. The algorithms in this study were divided into two groups including correction based and model based algorithms. Results: A total of 84 clinical test case datasets for different energies and calculation algorithms were produced, which amounts of differences in inhomogeneity points with low density (lung) and high density (bone) was decreased meaningfully with advanced algorithms. The number of deviations outside agreement criteria was increased with the beam energy and decreased with advancement of the TPS calculation algorithm. Conclusion: Large deviations were seen in some correction based algorithms, so sophisticated algorithms, would be preferred in clinical practices, especially for calculation in inhomogeneous media. Use of model based algorithms with lateral transport calculation, is recommended. Some systematic errors which were revealed during this study, is showing necessity of performing periodic audits on TPS in radiotherapy centers.

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.

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.

Introduction: This study aimed to calculate the photon and neutron doses received to the contralateral breast (CB) during breast cancer radiotherapy for various field sizes in the presence of a physical wedge. Materials and Methods: Varian 2100 C/D linear accelerator was simulated using a MCNP4C Monte Carlo code. Then, a phantom of real female chest was simulated and the treatment planning was carried out on tumoral breast (left breast). Finally, the received photon and neutron doses to CB (right breast) were calculated in the presence of a physical wedge for 18 MV photon beam energy. These calculations were performed for different field sizes including 11 cm × 13 cm, 11 cm × 17 cm, and 11 cm × 21 cm. Results: The findings showed that the received doses (both of the photon and neutron) to CB in the presence of a physical wedge for 11 cm × 13 cm, 11 cm × 17 cm, and 11 cm × 21 cm field sizes were 9.87%, 12.91%, and 27.37% of the prescribed dose, respectively. In addition, the results showed that the received photon and neutron doses to CB increased with increment in the field size. Conclusion: From the results of this study, it is concluded that the received photon and neutron doses to CB in the presence of a physical wedge is relatively more, and therefore, they should be reduced to as low as possible. Therefore, using a dynamic wedge instead of a physical wedge or field-in-field technique is suggested.

Brachytherapy treatment planning systems (BTPS) are employing the American Association of Physicists in Medicine (AAPM) Task Group 43 (TG‐43)‐recommended dosimetric parameters of sources, which are measured in water. The majority of brachytherapy implant volumes are not homogeneous media. Particularly, an implant with multiple seeds significantly changes homogeneity of the implant volume. Heterogeneities, such as attenuation by adjacent seeds or interseed attenuation (ISA), are neglected to this day in all BTPS. The goal of this project is to determine a novel analytical method to evaluate the impact of the dose perturbations (P‐value) and/or interseed attenuation effect (ISA‐value). This method will be validated for low‐ and high‐energy brachytherapy seeds such as 125I and 192Ir using Monte Carlo (MC) simulation techniques. In this analytical model, determination of dose perturbation and interseed attenuation in a multisource brachytherapy implant is based on MC‐simulated 3D kernels of P‐values and ISA data for single active and single dummy configurations, arranged at different distances and orientations relative to each other. The accuracy of the final model in multisource implant configurations has been examined by a comparison of the calculated P‐values and ISA‐values with full Monte Carlo water simulations (FMCWS). This model enabled us to determine the total perturbation and ISA values for any multisource implant, and the results are in excellent agreement with the FMCWS data. The advantage of this model to FMCWS for daily clinical application is the speed of the calculations and ease of the implementation. The new perturbation and ISA formulism have shown a better accuracy for 192Ir than 125I due to Compton scattering and its independence of the atomic number of the chemical composition of the phantom materials. The maximum difference between the ISA model and FMCWS for all cases was less than 5%. This new model can provide inputs for brachytherapy planning software to consider the ISA effect in dose calculations based on TG‐43U1 algorithm. This approach is applicable for energy range of 125I to 192Ir sources. PACS number: 87.53.Jw

Purpose To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Methods and Materials Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with α/β = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Results Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D 50 estimated from the models was approximately 44 Gy. Conclusions The implemented normal tissue complication probability models showed a parallel architecture for the thyroid. The mean dose model can be used as the best model to describe the dose-response relationship for hypothyroidism complication.

Purpose: To investigate the dosimetric characteristics of accelerated partial breast irradiation technique by MammoSite® applicator using thermoluminescent dosimeter (TLD) and Monte Carlo simulation to comparing them with treatment planning system calculation for planning target volume (PTV) and organs at risk such as skin, lung and chest wall. Materials and Methods: The Monte Carlo MCNP-5 code was used to simulate dose rate in the PTV that is a MammoSite® balloon with 1 cm margin around it. Experimental dosimetry was carried out within a female-equivalent chest phantom with TLD dosimeter after insertion of 192 Ir source into the MammoSite® applicator. Three dimensional planning (TP) was done for dose delivery to the specific points within the phantom by means of FlexiPlan software. Results: Statistical comparisons were done between TP calculation, Monte Carlo simulation and TLD. Our results showed good agreement for surface doses between simulation and measurement. The mean skin dose for the simulation and TLD result was 61.7% and 56.8% of prescription dose, respectively. The maximum dose to the chest wall for Monte Carlo and TLD were 114.4% and 111.8% of prescription dose, respectively. The maximum dose to the lung for Monte Carlo and TLD results were 28.4% and 27.3% of prescription dose, respectively. Using Monte Carlo simulation and an average female chest phantom, it was possible to demonstrate the accuracy on the calculated dose rate in the PTV of a MammoSite® dose delivery system with 192 Ir HDR sources. Conclusions: The results showed acceptable agreement between simulation, treatment planning, and experimental dosimetry results.

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

Background: The high-dose-rate (HDR) brachytherapy might be an effective tool for palliation of dysphagia. Because of some concerns about adverse effects due to absorbed radiation dose, it is important to estimate absorbed dose in risky organs during this treatment. Objectives: This study aimed to measure the absorbed dose in the parotid, thyroid, and submandibular gland, eye, trachea, spinal cord, and manubrium of sternum in brachytherapy in an anthropomorphic phantom. Materials and Methods: To measure radiation dose, eye, parotid, thyroid, and submandibular gland, spine, and sternum, an anthropomorphic phantom was considered with applicators to set thermoluminescence dosimeters (TLDs). A specific target volume of about 23 cm3 in the upper thoracic esophagus was considered as target, and phantom planned computed tomography (CT) for HDR brachytherapy, then with a micro-Selectron HDR (192Ir) remote after-loading unit. Results: Absorbed doses were measured with calibrated TLDs and were expressed in centi-Gray (cGy). In regions far from target (≥ 16 cm) such as submandibular, parotid and thyroid glands, mean measured dose ranged from 1.65 to 5.5 cGy. In closer regions (≤ 16 cm), the absorbed dose might be as high as 113 cGy. Conclusions: Our study showed similar depth and surface doses; in closer regions, the surface and depth doses differed significantly due to the role of primary radiation that had imposed a high-dose gradient and difference between the plan and measurement, which was more severe because of simplifications in tissue inhomogeneity, considered in TPS relative to phantom.

Purpose: To investigate the improvement in dose distribution in tangential breast radiotherapy using a reversible transverse magnetic field that maintains the same direction of Lorentz force between two fields. The investigation has a potential application in future Linac-MR units. Methods: Computed tomography images of four patients and magnetic fields of 0.25–1.5 Tesla (T) were used for Monte Carlo simulation. Two patients had intact breast while the other two had mastectomy. Simulations of planning and chest wall irradiation were similar to the actual clinical process. The direction of superior-inferior magnetic field for the medial treatment beam was reversed for the lateral beam. Results: For the ipsilateral lung and heart mean doses were reduced by a mean (range) of 45.8% (27.6%–58.6%) and 26.0% (20.2%–38.9%), respectively, depending on various treatment plan setups. The mean V{sub 20} for ipsilateral lung was reduced by 55.0% (43.6%–77.3%). In addition acceptable results were shown after simulation of 0.25 T magnetic field demonstrated in dose-volume reductions of the heart, ipsilateral lung, and noninvolved skin. Conclusions: Applying a reversible magnetic field during breast radiotherapy, not only reduces the dose to the lung and heart but also produces a sharp drop dose volume histogram for planning target volume, because ofmore » bending of the path of secondary charged particles toward the chest wall by the Lorentz force. The simulations have shown that use of the magnetic field at 1.5 T is not feasible for clinical applications due to the increase of ipsilateral chest wall skin dose in comparison to the conventional planning while 0.25 T is suitable for all patients due to dose reduction to the chest wall skin.« less

Purpose: GZP6 machine is used for high dose rate (HDR) brachytherapy treatment. In this project, treatment planning of GYN brachytherapy of this machine has been evaluated using a newly fabricated phantom along Gafchromic films and TG‐43 calculation. Methods: A new QA phantom has been designed and fabricated from 90 slabs of Perspex to accommodate ovoids assembly of GYN brachytherapy treatment. Two large oviods with 3 cm diameter was used for this assembly. EBT Gafchoromic films were exactly sandwiched between slabs and completely fitted to shape of ovoids for verification of GZP6 treatment planning. Plan designed to deliver 2.5 Gy dose to surface of oviods. The measured doses values at several points of interest were evaluated. The measured data were compared with the calculated values by the GZP6 treatment planning software. With seeing large difference between film dosimetry and planning, Air kerma strength (Sk) was obtained from Monte Carlo simulation and considered for TG‐43 calculation to reduce error. Results: The Result of these investigations have indicated differences of up to ± 23.4 % between the treatment planning and measured film dosimetry data at different points in GYN implant with GZP6 60Co HDR system. Between air kerma strength used in planning and Sk from simulation, 26% difference was calculated. TG‐43 calculation with simulated Sk can reduces difference between measurements to around 9%. Conclusion: The new phantom could be utilized for the QA procedure of the GZP6 60Co HDR system or the Ir‐192 HDR system to confirmation the accuracy of treatment planning in GYN implants and to find source of systematic errors.