Clinical Radiation Research Articles

Evaluation of an eLearning teaching innovation to assist clinical radiation therapy educators in the provision of student feedback

BackgroundClinical placement is an integral part of the Radiation Therapy undergraduate programme. Feedback and formative assessment during clinical placement are regarded as key to developing clinical skills and competencies. Students regularly report dissatisfaction with the feedback process while clinical educators report heavy clinical workloads and a lack of guidance on feedback mechanisms as barriers to providing meaningful student feedback. MethodsAn eLearning teaching intervention was developed to support radiation therapists in the provision of student feedback in the clinic. Thematic analysis was used to report attitudes to feedback and feedback practices collected in a pre and a post intervention evaluation. Results30 radiation therapists completed the module and pre and post intervention evaluations. Prior to taking the module just over half of respondents stated that they offered regular and on-going feedback throughout the student's placement. Positive attitudes to feedback were reported. Following completion of the eLearning tool respondents reported a higher level of confidence in the provision of student feedback and almost 70% said the module had changed how they would approach the feedback process by using feedback models in the future. DiscussionGood and timely feedback is essential and allows a student opportunity to improve prior to the end of the placement. It also teaches students how to self-assess and self-reflect - skills that they can use in continuous professional development after they graduate. Radiation therapists appreciate the structure that using a model in the feedback process offers. ConclusionThis eLearning teaching intervention was received favourably by radiation therapists who are key to creating a culture of feedback in the clinical environment that will facilitate students in becoming competent healthcare professionals.

Structural and dosimetric study of sub-kGy neutron-irradiated graphitic media

Associated with the marked difference between the mechanism of neutrons interactions relative to that of low linear-energy transfer (LET) radiations, few convenient dosimeters offer well differentiated measurement of neutron doses at useful sensitivity and spatial resolution. Present study has made use of highly uniform 2B and HB grade polymer pencil lead graphite (PPLG) (approximately 95 wt % and 61 wt % graphite content, respectively), addressing variation in lattice structure and defects resulting from sub-kGy neutron-doses. The latter have been provided by the TRIGA-II nuclear reactor located at the Bangladesh Atomic Energy Commission. Raman, photoluminescence (PL), and thermoluminescence (TL) techniques were used to perform structural and luminescence characterization of PPLGs. Comparison was made with highly-oriented pyrolytic graphite (HOPG), a pure ordered synthetic form of graphite. The dose-dependent defects produced in graphitic structures were characterized based on the Raman ID/IG intensity ratio, with observation of the Wigner effect. Analysis of PL spectra provides an average band gap energy in the range of 1.111–1.114 eV. All samples have been found to provide excellent linear response within the dose range 0–200 Gy, 2B grade PPLGs showing greater sensitivity compared to that of HB. The outcomes from this research may contribute to the development of cost effective, versatile graphite-based dosimeters, with particular applications to ionizing radiation dosimetry in clinical radiotherapy and industrial spheres.

Connexin26 Modulates the Radiosensitivity of Cutaneous Squamous Cell Carcinoma by Regulating the Activation of the MAPK/NF-κB Signaling Pathway.

Previous studies have confirmed that the gap junction protein Connexin26 (Cx26) is specifically expressed in human skin tissue. Cx26 can transmit radiation-induced damage signals. However, no study has yet reported whether Cx26 expression affects the radiosensitivity of human skin squamous cancer cells or the mechanism by which this occurs. In this study, we found that human skin squamous cell carcinoma cells (A431 cells) expressed significantly more Cx26 and were more sensitive to radiation compared to normal human keratinocytes (HaCaT cells). Knockdown of Cx26 in A431 cells (A431Cx26–/–) decreased radiosensitivity relative to control cells and altered the expression of key proteins in the MAPK and NF-κB signaling pathways. These results demonstrate that Cx26 expression might play an important role in mediating radiation damage in A431 cells and could serve as a potential target for clinical radiotherapy for cutaneous squamous cell carcinoma.

The effects of set-up errors on dose distribution in radiotherapy treatment for lung cancer

Background: Our aim was to analyze the effects of set-up errors on dose distribution in radiotherapy treatment for lung cancer by using kilovoltage cone-beam CT (CBCT). Materials and Methods: In this study, we used a Varian IX linear accelerator system to perform CBCT scans of 30 lung cancer patients before radiotherapy. Subsequently, the image was matched with the planned CT, and the left and right (LR), top and bottom (SI), and front and back (AP) directions were set incorrectly. And in the CMS planning system, the center of the plan has been moved to the center of the actual scan. Finally, the dose distribution before the bed-moving is simulated. We want to explore the impact of the planned target volume setting error (PTV), the total tumor volume (GTV), and radiation of normal tissues. Results: The set-up errors of the LR, SI and AP directions were (-0.20±2.84), (-1.09±5.40), and (-2.61±2.08) mm, respectively. The 5mm error accounted for 97.8%, 73% and 92.6% in the three directions. Statistically significant differences were found in the distribution of 95%PTV dose, the average dose of PTV, 95% GTV dose and the average dose of GTV without bed-moving, compared with the original plan. Conclusions: In clinical lung cancer radiotherapy, the commonly used setting error is usually less than 5mm, most of which are along the AP direction. In this study, we found that the setting error is related to the patient's inherent characteristics and can significantly change the radiation treatment dose in the target area.

Automation in radiotherapy treatment planning: Examples of use in clinical practice and future trends for a complete automated workflow

Modern radiotherapy treatment planning is a complex and time-consuming process that requires the skills of experienced users to obtain quality plans. Since the early 2000s, the automation of this planning process has become an important research topic in radiotherapy. Today, the first commercial automated treatment planning solutions are available and implemented in a growing number of clinical radiotherapy departments. It should be noted that these various commercial solutions are based on very different methods, implying a daily practice that varies from one center to another. It is likely that this change in planning practices is still in its infancy. Indeed, the rise of artificial intelligence methods, based in particular on deep learning, has recently revived research interest in this subject. The numerous articles currently being published announce a lasting and profound transformation of radiotherapy planning practices in the years to come. From this perspective, an evolution of initial training for clinical teams and the drafting of new quality assurance recommendations is desirable.

Diffuse large B-cell lymphoma segmentation in PET-CT images via hybrid learning for feature fusion.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of lymphoma with high mortality and poor prognosis that especially has a high incidence in Asia. Accurate segmentation of DLBCL lesions is crucial for clinical radiation therapy. However, manual delineation of DLBCL lesions is tedious and time-consuming. Automatic segmentation provides an alternative solution but is difficult for diffuse lesions without the sufficient utilization of multimodality information. Our work is the first study focusing on positron emission tomography and computed tomography (PET-CT) feature fusion for the DLBCL segmentation issue. We aim to improve the fusion performance of complementary information contained in PET-CT imaging with a hybrid learning module in the supervised convolutional neural network. First, two encoder branches extract single-modality features, respectively. Next, the hybrid learning component utilizes them to generate spatial fusion maps which can quantify the contribution of complementary information. Such feature fusion maps are then concatenated with specific-modality (i.e., PET and CT) feature maps to obtain a representation of the final fused feature maps in different scales. Finally, the reconstruction part of our network creates a prediction map of DLBCL lesions by integrating and up-sampling the final fused feature maps from encoder blocks in different scales. The ability of our method was evaluated to detect foreground and segment lesions in three independent body regions (nasopharynx, chest, and abdomen) of a set of 45 PET-CT scans. Extensive ablation experiments compared our method to four baseline techniques for multimodality fusion (input-level (IL) fusion, multichannel (MC) strategy, multibranch (MB) strategy, and quantitative weighting (QW) fusion). The results showed that our method achieved a high detection accuracy (99.63% in the nasopharynx, 99.51% in the chest, and 99.21% in the abdomen) and had the superiority in segmentation performance with the mean dice similarity coefficient (DSC) of 73.03% and the modified Hausdorff distance (MHD) of 4.39mm, when compared with the baselines (DSC: IL: 53.08%, MC: 63.59%, MB: 69.98%, and QW: 72.19%; MHD: IL: 12.16mm, MC: 6.46mm, MB: 4.83mm, and QW: 4.89mm). A promising segmentation method has been proposed for the challenging DLBCL lesions in PET-CT images, which improves the understanding of complementary information by feature fusion and may guide clinical radiotherapy. The statistically significant analysis based on P-value calculation has indicated a degree of significant difference between our proposed method and other baselines (almost metrics: P<0.05). This is a preliminary research using a small sample size, and we will collect data continually to achieve the larger verification study.

Metabolic reprograming of antioxidant defense: a precision medicine perspective for radiotherapy of lung cancer?

Radiotherapy plays a key role in the management of lung cancer patients in curative and palliative settings. Traditionally, radiotherapy was either given alone or in combination with surgery, classical cytotoxic chemotherapy, or both. Technical and physical innovations achieved during the last two decades have helped to enhance the accuracy of radiotherapy dose delivery and have facilitated geometric radiotherapy individualization. Furthermore, multimodal combinations with molecularly tailored drugs or immunotherapy yielded promising survival benefits in selected patients. Yet high locoregional failure rates and frequent development of metastases still limit the patient outcome. One major obstacle to successful treatment is the high molecular heterogeneity observed in lung cancer. So far, clinical radiotherapy does not routinely use the knowledge on molecular subtypes with regard to therapy individualization and predictive biomarkers are missing. Herein, altered cancer metabolism has attracted novel attention during recent years as it promotes tumor growth and progression as well as resistance to anticancer therapies. The present perspective will exemplarily highlight how clinically relevant molecular subtypes defined by co-occurring somatic mutations in KRAS-driven lung cancer impact the metabolic phenotype of cancer cells, how the metabolic phenotype supports intrinsic radioresistance by the improved antioxidant defense, and also discuss potential subtype-specific actionable metabolic vulnerabilities. Understanding metabolic phenotypes of radioresistance and metabolic bottlenecks of cancer cells undergoing radiotherapy in a cancer-specific context will offer largely unexploited future avenues for biological individualization and optimization of radiotherapy. Transcriptional profiles will provide additional benefit in defining metabolic phenotypes associated with radioresistance, particularly in cases, where such dependencies cannot be identified by specific somatic mutations.

Implementation of deep learning-based auto-segmentation for radiotherapy planning structures: a workflow study at two cancer centers

PurposeWe recently described the validation of deep learning-based auto-segmented contour (DC) models for organs at risk (OAR) and clinical target volumes (CTV). In this study, we evaluate the performance of implemented DC models in the clinical radiotherapy (RT) planning workflow and report on user experience.Methods and materialsDC models were implemented at two cancer centers and used to generate OAR and CTVs for all patients undergoing RT for a central nervous system (CNS), head and neck (H&N), or prostate cancer. Radiation Therapists/Dosimetrists and Radiation Oncologists completed post-contouring surveys rating the degree of edits required for DCs (1 = minimal, 5 = significant) and overall DC satisfaction (1 = poor, 5 = high). Unedited DCs were compared to the edited treatment approved contours using Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD).ResultsBetween September 19, 2019 and March 6, 2020, DCs were generated on approximately 551 eligible cases. 203 surveys were collected on 27 CNS, 54 H&N, and 93 prostate RT plans, resulting in an overall survey compliance rate of 32%. The majority of OAR DCs required minimal edits subjectively (mean editing score ≤ 2) and objectively (mean DSC and 95% HD was ≥ 0.90 and ≤ 2.0 mm). Mean OAR satisfaction score was 4.1 for CNS, 4.4 for H&N, and 4.6 for prostate structures. Overall CTV satisfaction score (n = 25), which encompassed the prostate, seminal vesicles, and neck lymph node volumes, was 4.1.ConclusionsPreviously validated OAR DC models for CNS, H&N, and prostate RT planning required minimal subjective and objective edits and resulted in a positive user experience, although low survey compliance was a concern. CTV DC model evaluation was even more limited, but high user satisfaction suggests that they may have served as appropriate starting points for patient specific edits.

Dosimetric investigation of non-coplanar field technology in static intensity-modulated radiation therapy for gastric carcinoma

Objective To compare the dosimetric characteristics of non-coplanar and coplanar field technology in static intensity-modulated radiotherapy of gastric cancer patients, so as to provide a reference for clinical radiotherapy plan selection. Methods Thirty-six patients with gastric cancer were selected to receive intensity-modulated radiotherapy in Huanggang Central Hospital, which was designed plan A and B. Group A used 7-field coplanar technology, while Group B used 7-fleld non-coplanar technology. We compared the differences of the optimized monitor unit, the dosimetry of organs at risk and target areas between group A and group B. Results Both group A and B could meet the requirements of doctors. The homogeneity index (0.14 ± 0.02), the conformity index (0.98 ± 0.01), D min (4 315.21 ± 16.74) cGy, D mean (4 679.28 ± 28.39) cGy and D max (4 952.30 ± 33.26) cGy of target areas in group B were better than those of group A. Moreover, the monitor unit of group B was much lower than that of group A, and the difference was statistically significant ( P < 0.05). The D max, D mean, V 15, V 20 and V 30 of the left and right kidneys in group B were lower than those of group A. The D max (3 408.57 ± 46.03) cGy, D mean (1 250.32 ± 14.27) cGy and V 20 (44.91% ± 6.67%) of spinal cord and the D max (3 408.57 ± 46.03) cGy, D mean (1 720.55 ± 17.42) cGy, V 20 (25.31% ± 7.78%) and V 30 (18.52% ± 1.56%) of small intestine were also lower than those of group A. The differences were statistically significant ( P < 0.05). Conclusion The non-coplanar field radiation plan has more advantages in terms of target dose distribution and protection of organs so that it can be more considerably used in the process of planning and design. 摘要： 目的 通过比较非共面射野与共面射野计划在胃癌静态调强中的剂量学特点, 为临床放疗计划选择提供依 据。 方法 选取黄冈市中心医院接受调强放射治疗的胃癌患者 36 例, 每名患者均设计A、B 2 组计划, A 组采用 7 野 共面技术, B 组采用 7 野非共面技术, 比较 A 组和 B 组优化后机器跳数、危及器官和靶区的剂量学差异。 结果 A、B 两组计划均能满足医生要求, B 组靶区均匀性指数 HI (0.14 ± 0.02)和适形度指数 CI (0.98 ± 0.01), 靶区 D min (4 315.21 ± 16.74) cGy, D mean (4 679.28 ± 28.39) cGy 和 D max (4 952.30 ± 33.26) cGy 均优于 A 组, 且 B 组机器跳数更 少, 差异有统计学意义 ( P < 0.05)。B 组左右侧肾脏 D max、 D mean、 V 15、 V 20 和 V 30均低于A组, 脊髓的 D max (3 408.57 ± 46.03) cGy、 D mean (1 250.32 ± 14.27) cGy 和 V 20 (44.91% ± 6.67%)以及小肠的 D max (3 408.57 ± 46.03) cGy、 D mean (1 720.55 ± 17.42) cGy、 V 20 (25.31% ± 7.78%) 和 V 30 18.52% ± 1.56%)也均低于 A 组, 差异有统计学意义 ( P < 0.05)。 结论 非共面射野计划在靶区剂量分布和危及器官保护上更优, 计划设计过程中可以更多的考虑非共面布野技术。

Survival Analysis and Prediction Model for Pulmonary Sarcomatoid Carcinoma Based on SEER Database.

ObjectiveThis study aimed to investigate the incidence of the pulmonary sarcomatoid carcinoma (PSC), to compare the clinical characteristics and overall survival (OS) of patients with PSC and those with other non-small-cell lung cancer (oNSCLC), so as to analyze the factors affecting the OS of patients with PSC and construct a nomogram prediction model.MethodsData of patients with PSC and those with oNSCLC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results database were collected. The age-adjusted incidence of PSC was calculated. The characteristics of patients with PSC and those with oNSCLC were compared, then the patients were matched 1:2 for further survival analysis. Patients with PSC were randomly divided into training set and testing set with a ratio of 7:3. The Cox proportional hazards model was used to identify the covariates associated with the OS. Significant covariates were used to construct the nomogram, and the C-index was calculated to measure the discrimination ability. The accuracy of the nomogram was compared with the tumor–node–metastasis (TNM) clinical stage, and the corresponding area under the curve was achieved.ResultsA total of 1049 patients with PSC were enrolled, the incidence of PSC was slowly decreased from 0.120/100,000 in 2004 to 0.092/100,000 in 2015. Before PSM, 793 PSC patients and 191356 oNSCLC patients were identified, the proportion of male, younger patients (<65 years), grade IV, TNM clinical stage IV was higher in the PSC. The patients with PSC had significantly poorer OS compared with those with oNSCLC. After PSM, PSC still had an extremely inferior prognosis. Age, sex, TNM clinical stage, chemotherapy, radiotherapy, and surgery were independent factors for OS. Next, a nomogram was established based on these factors, and the C-indexs were 0.775 and 0.790 for the training and testing set, respectively. Moreover, the nomogram model indicated a more comprehensive and accurate prediction than the TNM clinical stage.ConclusionsThe incidence of PSC was slowly decreased. PSC had a significantly poor prognosis compared with oNSCLC. The nomogram constructed in this study accurately predicted the prognosis of PSC, performed better than the TNM clinical stage.

Clinical Characteristics and Treatment Outcome of Paediatric Rhabdomyosarcoma; A Retrospective Review.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. This paper aimed to assess the stage, site and treatment outcome among RMS patients. A retrospective chart review was completed from January 2011 to December 2017 of patients that presented to the Department of Paediatric Oncology, Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, for the management of RMS. Data collection included clinical characteristics, staging, grouping, risk stratification, treatment plan, radiotherapy doses and treatment outcome. Among 24 subjects, there were a total of 13 (54.2%) males and 11 (45.8%) females. The median age at the time of diagnosis was 2.5 years (range: 0.75-17 years). The majority of the subjects (91.7%) were <10 years of age. The median follow-up time was 0.6 years. According to the Children's Oncology Group Classification, 4 (16.7%) subjects were classified as low risk, 14 (58.3%) subjects were rated as intermediate risk and 6 (0.25%) subjects were stratified as high risk. The most common primary tumour site was genitourinary (62.5%) and abdomen/retroperitoneal (20.8%) regions. At the time of analysis, nine (37.5%) subjects had died because of the disease, 12 (50%) were alive with no evidence of disease and one subject had a recurrence of disease and was alive. One subject had abandoned the therapy and another was lost to follow-up. Patients with RMS presented at the late stages of the disease and it most frequently affected genitourinary and abdomen or retroperitoneal areas. Overall, RMS was found to have a poor outcome to therapy.

Magnetic resonance biomarkers in radiation oncology: The report of AAPM Task Group 294.

PurposeA magnetic resonance (MR) biologic marker (biomarker) is a measurable quantitative characteristic that is an indicator of normal biological and pathogenetic processes or a response to therapeutic intervention derived from the MR imaging process. There is significant potential for MR biomarkers to facilitate personalized approaches to cancer care through more precise disease targeting by quantifying normal versus pathologic tissue function as well as toxicity to both radiation and chemotherapy. Both of which have the potential to increase the therapeutic ratio and provide earlier, more accurate monitoring of treatment response. The ongoing integration of MR into routine clinical radiation therapy (RT) planning and the development of MR guided radiation therapy systems is providing new opportunities for MR biomarkers to personalize and improve clinical outcomes. Their appropriate use, however, must be based on knowledge of the physical origin of the biomarker signal, the relationship to the underlying biological processes, and their strengths and limitations. The purpose of this report is to provide an educational resource describing MR biomarkers, the techniques used to quantify them, their strengths and weakness within the context of their application to radiation oncology so as to ensure their appropriate use and application within this field.

Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients.

FLASH radiotherapy has emerged as a treatment technique with great potential to increase the differential effect between normal tissue toxicity and tumor response compared to conventional radiotherapy. To evaluate the feasibility of FLASH radiotherapy in a relevant clinical setting, we have commenced a feasibility and safety study of FLASH radiotherapy in canine cancer patients with spontaneous superficial solid tumors or microscopic residual disease, using the electron beam of our modified clinical linear accelerator. The setup for FLASH radiotherapy was established using a short electron applicator with a nominal source-to-surface distance of 70 cm and custom-made Cerrobend blocks for collimation. The beam was characterized by measuring dose profiles and depth dose curves for various field sizes. Ten canine cancer patients were included in this initial study; seven patients with nine solid superficial tumors and three patients with microscopic disease. The administered dose ranged from 15 to 35 Gy. To ensure correct delivery of the prescribed dose, film measurements were performed prior to and during treatment, and a Farmer-type ion-chamber was used for monitoring. Treatments were found to be feasible, with partial response, complete response or stable disease recorded in 11/13 irradiated tumors. Adverse events observed at follow-up ranging from 3-6 months were mild and consisted of local alopecia, leukotricia, dry desquamation, mild erythema or swelling. One patient receiving a 35 Gy dose to the nasal planum, had a grade 3 skin adverse event. Dosimetric procedures, safety and an efficient clincal workflow for FLASH radiotherapy was established. The experience from this initial study will be used as a basis for a veterinary phase I/II clinical trial with more specific patient inclusion selection, and subsequently for human trials.

472 Addressing the Quality of Hospital Care of Colorectal Cancer Patients Undergoing Surgery: What Did We Learn from the National Bowel Cancer Audit?

Abstract Aim To identify the most relevant clinical factors in the National Bowel Cancer Audit (NBOCA) that contribute to the variation in the quality of care provided in different hospitals for colorectal cancer patients undergoing surgery. Method Data from 36,116 patients with colorectal cancer who had undergone surgery were retrospectively collected from the NBOCA and analysed from 145 and 146 hospitals over two years. A validated multiple linear regression was performed to compare the identified clinical factors with various quality outcomes. The quality outcomes defined in this study were the length of hospitalisation, 2-year mortality, readmission rate, 90-day mortality, and 18-month stoma rate. Results Four clinical factors (laparoscopy rate, abdominal-perineal-resection-of-rectum (APER), pre-operative radiotherapy and patients with distant metastases) were shown to have a significant (p &amp;lt; 0.05) impact on the length of hospitalisation and 18-month stoma rate. 18-month stoma rate was also significantly associated with 2-year mortality. External validation of the regression model demonstrated the Root-Mean-Square-Error of 0.811 and 4.62 for 18-month stoma rate and 2-year mortality respectively. Conclusions Hospitals should monitor the four clinical factors for patients with colorectal cancer during perioperative care. Clinicians should consider these factors along with the individual patients’ history when formulating a management plan for patients with colorectal cancer.

Evaluation of SrAl2 O4 :Eu, Dy phosphor for potential applications in thermoluminescent dosimetry.

PurposeTo evaluate the use of commercial‐grade strontium aluminate phosphorescent powder as a thermoluminescent (TL) dosimeter for clinical radiotherapy beams.Materials and MethodCommercially available Eu2+, Dy3+ co‐doped strontium aluminate powder (SrAl2O4:Eu, Dy) was annealed and then irradiated using 20 × 20 cm2 field size, with 6‐MV (PDD10 = 70.7) and 18‐MV (PDD10 = 79.4) photon beams and and 9‐MeV (R50 = 3.6), 15 MeV (R50 = 5.9) and 18‐MeV (R50 = 7.2) electron beams. To calibrate the relationship between the TL readings and the irradiated doses, TL glow curves were acquired for doses up to 600 cGy at all beam energies. For the percentage depth dose (PDD) measurement, the SrAl2O4:Eu, Dy powder was sandwiched by solid water phantoms, with varying thickness of solid water placed above to determine the depth. PDDs were measured at four representative depths and compared against the commissioning depth dose data for each beam energy.ResultsLinear dose response models of doses up to 200 cGy were created for all beam energies. Superlinearity was observed with doses greater than 200 cGy. The PDD measurement acquired experimentally agrees well with the commissioning data of the medical linear accelerator. Trapping parameters such as order of kinetics, activation energy and frequency factor have been obtained via TL glow curve analysis.ConclusionThe linear dose response demonstrates that SrAl2O4:Eu, Dy is a potential TLD dosimeter for both electron beams and photon beams at different beam energies. The PDD measurements further support its potential use in quality assurance and radiation dosimetry.

Expression profiles of radio-resistant genes in colorectal cancer cells

ObjectiveTo develop new biomarkers for radio-resistance in colorectal cancer (CRC) to improve radiotherapy efficacy at lower position and late phase of CRC patients. MethodsThe human CRC cell lines were irradiated by a total dose of 40 Gy. RAN-seq screened differentially expressed genes (DEGs) related to radio-resistance. We orientated the genes which play a vital role in radio-resistance by bio-informatics analysis. Ultimately, the genetic expressions were verified by qPCR. Results3,823radio-resistance genes were found in RKO cells and 4,057 DEGs were in HCT116 cells, compared with the same type cells without radiation treatment. Data of enrichment analysis showed that DEGs obtained from two cell lines were mainly involved in cell cycle, cell division, cell skeleton, cell adhesion, DNA replication, DNA damage and DNA repair, and enrichment of glycometabolism, p53 and HIF-1 signaling pathways. The 10 candidate biomarkers were predicted according to the interaction with each other, and 5 genes (CD44, CXCL-8, ITGA5, ITGB8 and STAT1) were confirmed markedly up-regulated in two cell lines. ConclusionRadio-resistance of CRC cells induced by X-irradiation changed the variety of genes expression, and those nodes among these genes network interaction may play core regulatory roles, which will provide new therapeutic strategies for clinical radiotherapy.

Predictive modeling of hypoxic head and neck cancers during fractionated radiotherapy with gold nanoparticle radiosensitization.

Intrinsic radioresistance and increased proliferation rates in head and neck cancers (HNCs) are associated with negative radiotherapy (RT) treatment responses. The use of gold nanoparticles (AuNPs) as radiosensitizers could enable total radiation dose reduction and lowered radiation toxicity. AuNP radiosensitization may overcome hypoxia-induced radioresistance and treatment-induced accelerated repopulation of cancer cells in HNCs, improving radiotherapy outcomes. Tumor control was determined by considering individual cancer cell responses in probabilistic computational simulations using HYP-RT software for clinical radiotherapy doses and fractionation schedules along with three different nanoparticle administration schedules. Antagonistic tumor hypoxia and rapid tumor regrowth due to accelerated repopulation of cancers cells were taken into consideration. Simulations indicate that tumors that are conventionally uncontrollable can be controlled with AuNP radiosensitization. In simulations where the absence of AuNPs required radiotherapy doses above standard clinical prescriptions, reoccurring AuNP administration allowed for radiation dose reductions below standard clinical dose prescriptions. For example, considering a 2Gy per fraction radiotherapy schedule, tumor control was achieved with 57.2±5.1Gy (P=<0.0001) for weekly AuNP administration and 53.0±4.0Gy (P=<0.0001) for biweekly AuNP administration compared to 69.9±5.8Gy with no radiosensitization. AuNPs decreased the predicted RT total doses required to achieve tumor control via total stem cell elimination, offering an optimistic prediction and method for which hypoxia-induced and rapidly growing radioresistant tumors are treated more effectively. Outcomes are also shown to be sensitive to the RT schedule with data for hyperfractionated RT indicating the greatest benefits from radiosensitization.

Effects of silencing circRNA ABCB10 expression on biological properties of colorectal cancer cells

Objective: To investigate the expression of circular ribonucleic acid ABCB10 (circABCB10) in colorectal cancer tissues and cells and its effects on cell biological behavior, radiosensitivity and growth of subcutaneous xenografts. Methods: The tumor tissue and adjacent tissue from colorectal cancer patients treated in Henan People's Hospital were collected from January 2018 to December 2018. Quantitative polymerase chain reaction (qPCR) was used to detect the expressions of circABCB10 and miR-217, cell viability was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT), cell apoptosis rate was detected by flow cytometry, cell migration and invasion were detected by Transwell method, cell radiosensitivity was detected by colony formation assay. The downstream miRNAs of circABCB10 were predicted by Circular RNA Interactome and verified by the dual luciferase reporter gene experiment. The effect of circABCB10 on the growth of transplanted tumor was examined in nude mice. Results: The expression level of circABCB10 mRNA in colorectal cancer tissues was (3.97±2.12), higher than (1.13±0.64) in adjacent tissues (P<0.05). The expression level of circABCB10 mRNA in FHC cells was (1.00±0.09), lower than that (4.53±0.44) in SW480, (3.12±0.32) in HCT116 and (3.51±0.36) in HT29 cells, respectively (all P<0.05). The MTT results showed that the absorbance values of SW480 cells in si-circABCB10-1 group at 48 and 72 hours after transfection were (0.36±0.04) and (0.43±0.04), lower than (0.48±0.05) and (0.82±0.08) in circ-negative control (NC) group, respectively (all P<0.05). The number of migrating cells and invasive cells in si-circABCB10-1 group were (45±8) and (34±7), lower than (106±21) and (84±15) in circ-NC group, respectively (all P<0.01). The radiosensitization ratio was 1.632. The results of subcutaneous transplantation assay showed that the tumor volume and tumor weight of the si-circABCB10-1 group were significantly lower than circ-NC group after 8 days of inoculation ( all P<0.05). MiR-217 is a target gene of circABCB10. Inhibition of miR-217 reversed the inhibitory effect of circABCB10 silencing on cell proliferation, migration, invasion and subcutaneous xenograft growth in nude mice and the radiosensitization activity. Conclusion: Silence of circABCB10 can up-regulate the expression of miR-217 to inhibit the proliferation, migration, invasion and growth of subcutaneous xenografts and increase the radiosensitivity of SW480 cells, which reveals the underlying molecular mechanism of colorectal cancer progression and provides a new sensitizing target for clinical radiotherapy of colorectal cancer.

First experience of autonomous, un-supervised treatment planning integrated in adaptive MR-guided radiotherapy and delivered to a patient with prostate cancer

Background and purposeCurrently clinical radiotherapy (RT) planning consists of a multi-step routine procedure requiring human interaction which often results in a time-consuming and fragmented process with limited robustness. Here we present an autonomous un-supervised treatment planning approach, integrated as basis for online adaptive magnetic resonance guided RT (MRgRT), which was delivered to a prostate cancer patient as a first-in-human experience. Materials and methodsFor an intermediate risk prostate cancer patient OARs and targets were automatically segmented using a deep learning-based software and logical volume operators. A baseline plan for the 1.5 T MR-Linac (20x3 Gy) was automatically generated using particle swarm optimization (PSO) without any human interaction. Plan quality was evaluated by predefined dosimetric criteria including appropriate tolerances. Online plan adaptation during clinical MRgRT was defined as first checkpoint for human interaction. ResultsOARs and targets were successfully segmented (3 min) and used for automatic plan optimization (300 min). The autonomous generated plan satisfied 12/16 dosimetric criteria, however all remained within tolerance. Without prior human validation, this baseline plan was successfully used during online MRgRT plan adaptation, where 14/16 criteria were fulfilled. As postulated, human interaction was necessary only during plan adaptation. ConclusionAutonomous, un-supervised data preparation and treatment planning was first-in-human shown to be feasible for adaptive MRgRT and successfully applied. The checkpoint for first human intervention was at the time of online MRgRT plan adaptation. Autonomous planning reduced the time delay between simulation and start of RT and may thus allow for real-time MRgRT applications in the future.

Properties and gene expression profiling of acquired radioresistance in mouse breast cancer cells.

BackgroundAcquired radioresistant cells exhibit many characteristic changes which may influence cancer progression and further treatment options. The purpose of this study is to investigate the changes of radioresistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells on both phenotypic and molecular levels.MethodsWe established an acquired radioresistant cell line from its parental NF639 cell line (HER2-positive) by fractionated radiation and assessed changes in cellular morphology, proliferation, migration, anti-apoptosis activity, basal reactive oxygen species (ROS) level and energy metabolism. RNA-sequencing (RNA-seq) was also used to reveal the potential regulating genes and molecular mechanisms associated with the acquired changed phenotypes. Real-time PCR was used to validate the results of RNA-seq.ResultsThe NF639R cells exhibited increased radioresistance and enhanced activity of proliferation, migration and anti-apoptosis, but decreased basal ROS. Two main energy metabolism pathways, mitochondrial respiration and glycolytic, were also upregulated. Furthermore, 490 differentially expressed genes were identified by RNA-seq. Enrichment analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed many differently expressed genes were significantly enriched in cell morphology, proliferation, migration, anti-apoptosis, antioxidation, tumor stem cells and energy metabolism and the signaling cascades such as the transforming growth factor-β, Wnt, Hedgehog, vascular endothelial growth factor, retinoic acid-inducible gene I (RIG-I)-like receptor, Toll-like receptor and nucleotide oligomerization domain (NOD)-like receptor were significantly altered in NF639R cells.ConclusionsIn clinical radiotherapy, repeat radiotherapy for short-term recurrence of breast cancer may result in enhanced radioresistance and promote malignant progression. Our research provided hints to understand the tumor resistance to radiotherapy de novo and recurrence with a worse prognosis following radiotherapy.