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

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

Butein combined with radiotherapy enhances radioresponse of gastric cancer cell by impairing DNA damage repair.

Radiation therapy is common in the current procedures of cancer treatment, but in many cases, radiation resistance of cancerous tissue limits efficacy in clinical applications. Therefore, the use of radiosensitizers has been introduced as an effective strategy to increase the efficiency of radiotherapy. Butein (2', 3, 4, 4'-Tetrahydroxychalcone), a polyphenolic compound of flavonoids family, presents anti-cancer properties and inhibits the signaling pathways associated with radiation resistance. Therefore, we hypothesized that butein in combination with radiation may increase radiosensitivity. To evaluate the radiosensitizing effect of butein, we used MKN-45 cell line and performed several assays such as MTT, soft-agar colony formation, apoptosis, cell cycle, and comet assays. Based on obtained results, butein significantly enhanced radiosensitivity of MKN-45 cells. Butein treatment abrogated the radiation-induced G2/M cell cycle arrest, increased DNA damage, enhanced apoptosis, and reduced colony-forming ability of irradiated cells. This study on MKN-45 cells demonstrates that combination of butein with radiotherapy increases its radiosensitivity by abrogating the radiation-induced G2/M blockage, impairing DNA repair, and enhancing apoptotic and reproductive cell death. Therefore, we suggest butein as a candidate for combination with radiation therapy to decrease dose of radiation delivered to the patients and its corresponding side effects.

Comparison of the Pathological Response and Adverse Effects of Oxaliplatin and Capecitabine versus Paclitaxel and Carboplatin in the Neoadjuvant Chemoradiotherapy Treatment Approach for Esophageal and Gastroesophageal Junction Cancer: A Randomized Control Trial Study.

Background: Neoadjuvant chemoradiation is one of the main treatment approaches in esophageal cancer treatment, which can improve outcomes of a patient with esophageal cancer. In the current study, we aimed to compare the response rate and side effects of 2 distinctive neoadjuvant chemoradiation protocols. Methods: The study was a randomized clinical trial that was performed on 70 patients with esophageal and gastroesophageal junction cancer in Iran. The study participants were randomly assigned to 1 of our treatment groups. The first group received capecitabine (625 mg/m2/TID) and oxaliplatin (50 mg/m2/weekly), while the second group was given a combination of carboplatin (AUC:2/weekly) and paclitaxel (75mg/m2/weekly). Both groups were given weekly 50.4-54 Gy dose of RT. Chi square and Fisher exact tests have been used for data analysis. All statistical tests were performed using SPSS software Version 22.0 and the significance level was set at 0.05. Results: Complete pathological response was detected in 18(51.4%) of patients in group I and 8 (22.8%) in group II (p=0.013). We also observed higher thrombocytopenia in CarTax arm 19 (54.2%) in comparison to CapOX arm 8(22.8%), and the difference was statistically significant (p=0.007). No statistical difference was found regarding neutropenia, fatigue, anorexia, esophagitis, and diarrhea. Conclusion: The CapOxRT regime provides more favorable outcomes and also it is more tolerated by patients.

Enterolactone: A novel radiosensitizer for human breast cancer cell lines through impaired DNA repair and increased apoptosis.

INTRODUCTION: Radiotherapy is a potent treatment against breast cancer, which is the most commonly diagnosed cancer among women. However, the emergence of radioresistance due to increased DNA repair leads to radiotherapeutic failure. Applying polyphenols combined with radiation is a more promising method leading to better survival. Enterolactone, a phytoestrogenic polyphenol, has been reported to inhibit an important radioresistance signaling pathway, therefore we conjectured that enterolactone could enhance radiosensitivity in breast cancer. To assess this hypothesis, radiation response of enterolactone treated MDA-MB-231 and T47D cell lines and corresponding cellular mechanisms were investigated. METHODS: Cytotoxicity of enterolactone was measured via MTT assay. Cells were treated with enterolactone before X-irradiation, and clonogenic assay was used to evaluate radiosensitivity. Cell cycle distribution and apoptosis were measured by flow cytometric analysis. In addition, DNA damages and corresponding repair, chromosomal damages, and aberrations were assessed by comet, micronucleus, and cytogenetic assays, respectively. RESULTS: Enterolactone decreased the viability of cells in a concentration- and time dependent manner. Enterolactone significantly enhanced radiosensitivity of cells by abrogating G2/M arrest, impairing DNA repair, and increasing radiation-induced apoptosis. Furthermore, increased chromosomal damages and aberrations were detected in cells treated with enterolactone combined with X-rays than X-ray alone. These effects were more prominent in T47D than MDA-MB-231 cells. DISCUSSION: To our knowledge, this is the first report that enterolactone is a novel radiosensitizer for breast cancer irrespective of estrogen receptor status. Authors propose enterolactone as a candidate for combined therapy to decrease the radiation dose delivered to patients and subsequent side effects.

Antimanic drug sensitizes breast cancer cell line to ionizing radiation.

Breast cancer is one of the most prevalent types of cancer among women. Lithium chloride (LiCl) is an FDA-approved drug for bipolar disorder. Breast cancer is reported to occur with higher rate in women with bipolar disorder. The effect of LiCl on the response of breast cancer cells to ionizing radiation has not been studied. We studied the effect of LiCl on the radiosensitivity of radioresistant T47D breast cancer cell line. Treatment of T47D cells with 20 mM LiCl for 24 hours decreased the radioresistance of these cells indicated by clonogenic survival assay. Comet assay demonstrated decreased DNA repair in LiCl-treated cells. LiCl treatment also decreased the meiotic recombination 11 (Mre11) mRNA level. Mre11 is an essential protein for DNA repair whose transcription is regulated by ß-catenin protein. Western blot analysis indicated that the ß-catenin protein level was decreased in LiCl-treated cells. LiCl increased glycogen synthase kinase-3ß (GSK-3ß) protein that is involved in ß-catenin degradation. The results demonstrated that LiCl could radiosensitize T47D cells by decreasing DNA repair, partially through Mre11 repression. GSK-3ß/ß-catenin/Mre11 pathway might be the connection between LiCl treatment and the decreased DNA repair in T47D cells.

Gossypol enhances radiation induced autophagy in glioblastoma multiforme.

Malignant gliomas (glioblastoma multiforme) are the most aggressive of the primary brain tumors. Radiotherapy is an important tool for treatment of cancer but malignant gliomas are usually resistant to radiotherapy and other adjuvant therapies. Thus new drugs are needed to increase the efficiency of radiotherapy in order to improve the therapeutic outcome of tumor patients. Recent investigations showed that gossypol, natural polyphenolic compound produced by cotton plants, is a promising agent against solid tumors. The current study was defined to evaluate whether the combinatorial effect of radiation and gossypol would induce higher level of cell death on U-87 MG than single agent treatment and its possible mechanism of action. Clonogenic survival assay showed that ionizing radiation plus gossypol significantly inhibited clonogenic growth of irradiated cells as compared with either treatment alone. Acridine orange/etidium bromide staining confirmed that there was no significant increase in necrotic and apoptotic cells, but irradiated cells in combination with gossypol showed a significant increase in accumulation of acidic vesicular organelle. The results obtained herein indicated that gossypol is a promising drug that induced autophagic cell death in radioresistant malignant glioma.

Prediction of auditory brain stem responses damage in patients with head-and-neck cancers receiving radiotherapy using the functional assays of normal tissue complication probability models.

AIM: The purpose of this study was to set four NTCP models on clinical data and develop a model that calculates the possibility of hearing damage due to irradiation of healthy and at-risk brainstem tissue. MATERIALS AND METHODS: ABR tests were performed on 50 head-and-neck cancer patients three years after radiotherapy for evaluation of lesions in a part of the auditory nerve or the auditory pathway in the brainstem. RESULTS: It indicated a significant difference in the latency of the waves assessed by the ABR test between the two groups. The paired sample t-test indicated the latency time of waves I, III, V, I-III, and I-V (P < 0.001) in the right ear, and in the left ear latency time of waves III, V, I-III, I-V, and III-V (P < 0.001) were significantly higher in the case group's ear than those in the control group. The confidence interval of the fitted parameters was 95% for NTCP models. ABR test's binary outcome with differential dose-volume histograms (dDVHs) was calculated and imported as input to the NTCP modeling. The values of the parameters n = 2.3-2.9 and the value s = 1 were obtained, which indicated that the brainstem organ is seriality. CONCLUSION: The best model ranked for the prediction of brainstem hearing damage was the logit model, which had the lowest Akaike value. The nervousness of the auditory organ of the brainstem (VIII nerve) can be declared as one of the reasons for being independent of the received dose.

A dosiomics model for prediction of radiation-induced acute skin toxicity in breast cancer patients: machine learning-based study for a closed bore linac.

BACKGROUND: Radiation induced acute skin toxicity (AST) is considered as a common side effect of breast radiation therapy. The goal of this study was to design dosiomics-based machine learning (ML) models for prediction of AST, to enable creating optimized treatment plans for high-risk individuals. METHODS: Dosiomics features extracted using Pyradiomics tool (v3.0.1), along with treatment plan-derived dose volume histograms (DVHs), and patient-specific treatment-related (PTR) data of breast cancer patients were used for modeling. Clinical scoring was done using the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 criteria for skin-specific symptoms. The 52 breast cancer patients were grouped into AST 2 + (CTCAE ≥ 2) and AST 2 - (CTCAE < 2) toxicity grades to facilitate AST modeling. They were randomly divided into training (70%) and testing (30%) cohorts. Multiple prediction models were assessed through multivariate analysis, incorporating different combinations of feature groups (dosiomics, DVH, and PTR) individually and collectively. In total, seven unique combinations, along with seven classification algorithms, were considered after feature selection. The performance of each model was evaluated on the test group using the area under the receiver operating characteristic curve (AUC) and f1-score. Accuracy, precision, and recall of each model were also studied. Statistical analysis involved features differences between AST 2 - and AST 2 + groups and cutoff value calculations. RESULTS: Results showed that 44% of the patients developed AST 2 + after Tomotherapy. The dosiomics (DOS) model, developed using dosiomics features, exhibited a noteworthy improvement in AUC (up to 0.78), when spatial information is preserved in the dose distribution, compared to DVH features (up to 0.71). Furthermore, a baseline ML model created using only PTR features for comparison with DOS models showed the significance of dosiomics in early AST prediction. By employing the Extra Tree (ET) classifiers, the DOS + DVH + PTR model achieved a statistically significant improved performance in terms of AUC (0.83; 95% CI 0.71-0.90), accuracy (0.70), precision (0.74) and sensitivity (0.72) compared to other models. CONCLUSIONS: This study confirmed the benefit of dosiomics-based ML in the prediction of AST. However, the combination of dosiomics, DVH, and PTR yields significant improvement in AST prediction. The results of this study provide the opportunity for timely interventions to prevent the occurrence of radiation induced AST.

Total Neoadjuvant vs. Standard Perioperative Cisplatin/ Doxorubicin Chemotherapy in Patients with Extremities Osteosarcoma: A Multi-Center Cohort Study.

INTRODUCTION: Despite improvements in survival of patients with high-grade osteosarcoma after the implementation of perioperative chemotherapy, osteosarcoma remains among the most lethal cancers. Prescription of all chemotherapy courses before the surgery may provide this opportunity to eliminate micrometastases more efficiently, increase the chances of pathologic complete response and organ preserving surgery. This study aimed to compare the outcomes of total neoadjuvant chemotherapy vs. standard perioperative chemotherapy with cisplatin/doxorubicin regimen in patients with extremities osteosarcoma. METHODS: In this retrospective cohort, all patients with high-grade osteosarcoma admitted to oncologic centers affiliated to Iran University of Medical Sciences in Tehran, Iran from 2015 to 2021 were included. Organ preserving rates, pathologic responses, and survival of patients who received all six courses of cisplatin/doxorubicin regimen preoperatively were compared to those who received the regimen perioperatively. RESULTS: Sixty-three patients were enrolled (total neoadjuvant chemotherapy: 32 patients and perioperative chemotherapy: 31 patients). In total neoadjuvant chemotherapy and perioperative chemotherapy groups, favorable pathology responses (necrosis>90%) were reported in 80.6% and 15.6% of patients, respectively (p<0.001). With a median follow-up of 24 months, mean overall survival of total neoadjuvant chemotherapy and perioperative chemotherapy groups were 21.29 months (95% CI; 19.3-23.27) and 23.46 months (95% CI; 22.7-24.1), respectively (p=0.2). The mean disease-free survival of patients in total neoadjuvant chemotherapy and perioperative chemotherapy groups were 19.54 months (95% CI; 17.0-22.0) and 21.37 months (95% CI; 19.4-23.2), respectively (p=0.2). CONCLUSION: Our results showed that prescription of all courses of doxorubicin/cisplatin chemotherapy prior to surgery can increase favorable pathologic response rates, although this improvement is not translated into overall and disease-free survival benefits.

A machine learning approach for prediction of auditory brain stem response in patients after head-and-neck radiation therapy.

Objective: The present study aimed to assess machine learning (ML) models according to radiomic features to predict ototoxicity using auditory brain stem responses (ABRs) in patients with radiation therapy (RT) for head-and-neck cancers. Materials and Methods: The ABR test was performed on 50 patients having head-and-neck RT. Radiomic features were extracted from the brain stem in computed tomography images to generate a radiomic signature. Moreover, accuracy, sensitivity, specificity, the area under the curve, and mean cross-validation were used to evaluate six different ML models. Results: Out of 50 patients, 21 participants experienced ototoxicity. Furthermore, 140 radiomic features were extracted from the segmented area. Among the six ML models, the Random Forest method with 77% accuracy provided the best result. Conclusion: According to the ML approach, we showed the relatively high prediction power of the radiomic features in radiation-induced ototoxicity. To better predict the outcomes, future studies on a larger number of participants are recommended.

Non-thermal CO2 Laser Therapy (NTCLT): A Novel Photobiomodulative Approach for Immediate Pain Relief of Patchy Oral Mucositis Due to Chemotherapy of Solid Tumors.

Introduction: Chemotherapy-induced oral mucositis (COM) is a prominent complication of chemotherapy (CT). Non-thermal CO2 laser therapy (NTCLT) has been demonstrated as an innovative and safe photobiomodulative approach in some kinds of painful oral lesions. The purpose of this study was to evaluate the palliative effects of one session of NTCLT on COM lesions. Methods: Patients with painful COM (WHO grade:≥2) were included in this before-after clinical trial based on the eligibility criteria. The oral lesions were irradiated with a CO2 laser (power: 1 W, scanning the lesions with the rapid circular motion of the defocused handpiece) through a thick layer (3-4 mm) of a transparent gel containing a high-water content. The severity of pain in the lesions was self-assessed using a 0-to-10 visual analogue scale (VAS) for 7 consecutive days. The evaluating physician visited the patients on the 3rd and 7th days in search of any kind of complications. Results: Seventeen adult patients with 35 patches of OM due to chemotherapy of solid tumors completed the trial. Immediately after NTCLT, the mean for non-contact VAS pain scores of the lesions significantly declined from 4.91±2.356 to 0.29±0.622 (P<0.001) and the mean for contact VAS pain scores from 7.77±1.57 to 1.31±1.18 (P<0.001). The mean VAS pain scores of the lesions showed statistically significant differences between the follow-up periods compared to the baseline (P<0.001). The process was completely pain-free and required no anesthesia. After NTCLT, no kind of thermal adverse effects such as irritation, destruction, aggravation and even erythema were observed. Conclusion: Based on the results of this before-after clinical trial, NTCLT has the potential to be considered as a non-invasive and safe palliative option for the pain management of patchy OM due to chemotherapy of solid tumors.

Expanding CYLD protein in NF-κß/TNF-α signaling pathway in response to Lactobacillus acidophilus in non-metastatic rectal cancer patients.

The CYLD gene is a tumor suppressor, reduced in many cancers. Here, we aimed to investigate CYLD protein level and NF-κß/TNF-α signaling pathway in rectal cancer patients with Lactobacillus acidophilus (L. acidophilus) consumption. One hundred ten patients with non-metastatic rectal cancer were randomly divided into L. acidophilus probiotic (500 mg, three times daily) and placebo groups for 13 weeks. The expression of CYLD, TNF-α, and NF-κB proteins and the genes involved in the NF-κß/TNF-α pathway were evaluated using ELISA and qPCR techniques. The survival rate was measured after five years. Unlike the placebo group, the results showed a significant increase in the expression of CYLD protein and tumor suppressor genes, including FOXP3, ROR-γ, Caspase3, GATA3, T-bet, and a considerable decrease in the expression of NF-Òß and TNF-α proteins and oncogenes, including STAT3, 4, 5, 6, and SMAD 3, in the probiotic group. A higher overall survival rate was seen after L. acidophilus consumption compared to the placebo group (P < 0.05). L. acidophilus consumption can reduce inflammation factors by affecting CYLD protein and its downstream signaling pathways. A schematic plot of probiotic consumption Effects on the CYLD protein in regulating the NF-Ä¸ß signaling pathway in colorectal cancer. NF-Ä¸ß can be activated by canonical and noncanonical pathways, which rely on IκB degradation and p100 processing, respectively. In the canonical NF-κß pathway, dimmers, such as p65/p50, are maintained in the cytoplasm by interacting with an IκBα protein. The binding of a ligand to a cell-surface receptor activates TRAF2, which triggers an IKK complex, containing -α, -ß, -g, which phosphorylates IKK-ß. It then phosphorylates IκB-α, leading to K48-ubiquitination and degradation of this protein. The p65/p50 protein freely enters the nucleus to turn on target genes. The non-canonical pathway is primarily involved in p100/RelB activation. It differs from the classical pathway in that only certain receptor signals activate this pathway. It proceeds through an IKK complex that contains two IKK-α subunits but not NEMO. Several materials including peptidoglycan, phorbol, myristate, acetate, and gram-positive bacteria such as probiotics inhibit NF-κB by inducing CYLD. This protein can block the canonical and noncanonical NF-κß pathways by removing Lys-63 ubiquitinated chains from activated TRAFs, RIP, NEMO, and IKK (α, ß, and γ). Moreover, TNF-α induces apoptosis by binding caspase-3 to FADD.

Prediction of chronic kidney disease in abdominal cancers radiation therapy using the functional assays of normal tissue complication probability models.

Aim: The purpose of this study is to predict chronic kidney disease (CKD) in the radiotherapy of abdominal cancers by evaluating clinical and functional assays of normal tissue complication probability (NTCP) models. Materials and Methods: Radiation renal damage was analyzed in 50 patients with abdominal cancers 12 months after radiotherapy through a clinical estimated glomerular filtration rate (eGFR). According to the common terminology criteria for the scoring system of adverse events, Grade 2 CKD (eGFR ≤30-59 ml/min/1.73 m2) was considered as the radiation therapy endpoint. Modeling and parameter estimation of NTCP models were performed for the Lyman-equivalent uniform dose (EUD), the logit-EUD critical volume (CV), the relative seriality, and the mean dose model. Results: The confidence interval of the fitted parameters was 95%. The parameter value of D50 was obtained 22-38 Gy, and the n and s parameters were equivalent to 0.006 -3 and 1, respectively. According to the Akaike's information criterion, the mean dose model predicts radiation-induced CKD more accurately than the other models. Conclusion: Although the renal medulla consists of many nephrons arranged in parallel, each nephron has a seriality architecture as renal functional subunits. Therefore, based on this principle and modeling results in this study, the whole kidney organs may have a serial-parallel combination or a secret architecture.

Radiomics analysis on CT images for prediction of radiation-induced kidney damage by machine learning models.

INTRODUCTION: We aimed to assess the power of radiomic features based on computed tomography to predict risk of chronic kidney disease in patients undergoing radiation therapy of abdominal cancers. METHODS: 50 patients were evaluated for chronic kidney disease 12 months after completion of abdominal radiation therapy. At the first step, the region of interest was automatically extracted using deep learning models in computed tomography images. Afterward, a combination of radiomic and clinical features was extracted from the region of interest to build a radiomic signature. Finally, six popular classifiers, including Bernoulli Naive Bayes, Decision Tree, Gradient Boosting Decision Trees, K-Nearest Neighbor, Random Forest, and Support Vector Machine, were used to predict chronic kidney disease. Evaluation criteria were as follows: accuracy, sensitivity, specificity, and area under the ROC curve. RESULTS: Most of the patients (58%) experienced chronic kidney disease. A total of 140 radiomic features were extracted from the segmented area. Among the six classifiers, Random Forest performed best with the accuracy and AUC of 94% and 0.99, respectively. CONCLUSION: Based on the quantitative results, we showed that a combination of radiomic and clinical features could predict chronic kidney radiation toxicities. The effect of factors such as renal radiation dose, irradiated renal volume, and urine volume 24-h on CKD was proved in this study.

Investigating dose homogeneity in radiotherapy of oral cancers in the presence of a dental implant system: an in vitro phantom study.

BACKGROUND: Materials with high atomic numbers are part of the composition of dental implant systems. In radiotherapy of oral cavity cancers, an implant can cause dose perturbations that affect target definition, dose calculation, and dose distribution. In consequence, this may result in poor tumor control and higher complications. In this study, we evaluated dose homogeneity when a dental implant replaced a normal tooth. We also aimed to evaluate the concordance of dose calculations with dose measurements. MATERIALS AND METHODS: In this study, 2 sets of planning CT scans of a phantom with a normal tooth and the same phantom with the tooth replaced by a Z1 TBR dental implant system were used. The implant system was composed of a porcelain-fused-to-metal crown and titanium with a zirconium collar. Three radiotherapy plans were designed when the density of the implant material was corrected to match their elements, or when all were set to the density of water, or when using the default density conversion. Gafchromic EBT-3 films at the level of isocenter and crowns were used for measurements. RESULTS: At the level of crowns, upstream and downstream dose calculations were reduced when metal kernels were applied (M-plan). Moreover, relatively measured dose distribution patterns were most similar to M-plan. At this level, relative to the non-implanted phantom, mean doses values were higher with the implant (215.93 vs. 192.25), also, new high-dose areas appeared around a low-dose streak forward to the implant (119% vs. 95%). CONCLUSIONS: Implants can cause a high dose to the oral cavity in radiotherapy because of extra scattered radiation. Knowledge of the implant dimensions and defining their material enhances the accuracy of calculations.

Comparison of radiation and chemoradiation-induced sensorineural hearing loss in head and neck cancer patients.

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.

Differential miRNAs expression pattern of irradiated breast cancer cell lines is correlated with radiation sensitivity.

Radiotherapy is a fundamental step in the treatment of breast cancer patients. The treatment efficiency is however reduced by the possible onset of radiation resistance. In order to develop the effective treatment approach, it is important to understand molecular basis of radiosensitivity in breast cancer. The purpose of the present study was to investigate different radiation response of breast cancer cell lines, and find out if this response may be related to change in the microRNAs expression profile. MDA-MB-231 and T47D cells were subjected to different doses of radiation, then MTT and clonogenic assays were performed to assess radiation sensitivity. Cytofluorometric and western blot analysis were performed to gain insight into cell cycle distribution and protein expression. MicroRNA sequencing and bioinformatics prediction methods were used to identify the difference in microRNAs expression between two breast cancer cells and the related genes and pathways. T47D cells were more sensitive to radiation respect to MDA-MB-231 cells as demonstrated by a remarkable G2 cell cycle arrest followed by a greater reduction in cell viability and colony forming ability. Accordingly, T47D cells showed higher increase in the phosphorylation of ATM, TP53 and CDK1 (markers of radiation response) and faster and more pronounced increase in RAD51 and γH2AX expression (markers of DNA damage), when compared to MDA-MB-231 cells. The two cell lines had different microRNAs expression profiles with a confirmed significant differential expression of miR-16-5p, which targets cell cycle related genes and predicts longer overall survival of breast cancer patients, as determined by bioinformatics analysis. These results suggest a possible role for miR-16-5p as radiation sensitizing microRNA and as prognostic/predictive biomarker in breast cancer.

Photobiomodulation leads to enhanced radiosensitivity through induction of apoptosis and autophagy in human cervical cancer cells.

The radiomodulatory effect of photobiomodulation (PBM) has recently been studied in cancer cells. The aim of this study was to investigate cellular mechanisms involved in the X-ray radiosensitivity of HeLa cells pre-exposed to PBM. HeLa cells were irradiated with 685 nm laser at different energy densities prior to X-ray ionizing radiation. After irradiation, clonogenic cell survival, cell death due to apoptosis and autophagy were determined. Levels of intracellular reactive oxygen species (ROS), DNA damage and, cell cycle distribution after PBM were measured. PBM at different energy densities (5-20 J/cm2 ) was not cytotoxic. However, HeLa cells pre-exposed to 20 J/cm2 showed enhanced inhibition of colony formation following ionizing radiation. Enhanced radiosensitivity was due to increased oxidative stress, DNA damage, and radiation-induced apoptosis and autophagy. These results suggest that 685 nm PBM at a higher energy density could possibly be a promising radiosensitizing agent in cervical cancer, to decrease the radiation dose delivered, and therefore prevent the side-effects that are associated with cancer radiotherapy.

Multi-parametric Improvements in the CCD Camera-based EPID for Portal Dosimetry.

Dosimetric verification of radiation treatment has recently been extended by the introduction of electronic portal imaging devices (EPIDs). Detailed dose response specifications of EPID should be addressed prior to any dosimetric application. The present study evaluates improvements of dosimetric properties of the low elbow camera-based EPID Theraview (Cablon Medical, Leusden, The Netherlands) equipped with a cooled charge coupled device (CCD) for portal dosimetry. The dose response, warm-up behavior, stability over long- and short-term scales (throughout a day) were studied. The field size dependency of the EPID response was also investigated and compared with ion chamber measurements under the same conditions. The EPID response without saturation for doses up to 2 Gy was linear for both beam qualities (6 and 15 MV). There was no evident warm-up characteristic. The detector sensitivity showed excellent stability in short term [standard deviation (SD) 0.38%]. In long-term stability (over a period of approximately 3 months), a negligible linear decline of 0.01% per day was observed. It was concluded that the cooled CCD camera-based EPID could be used for portal dosimetry, after accurate corrections for the field size dependency and sensitivity loss.

Normal tissue complication probability modeling of radiation-induced sensorineural hearing loss after head-and-neck radiation therapy.

PURPOSE: 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). MATERIALS AND METHODS: 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. RESULTS: The dose of 50% complication rate (D50) was 51-60 Gy. Three of the examined models fitted well with clinical data in a 95% confidence interval. The RS model was ranked as the best model of prediction for radiation induced SNHL. CONCLUSIONS: Cochlea shows a different behavior against different NTCP models; it may be due to its small size.