IROCA-TES: Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization.

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices. Materials and methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization). Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice. Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres.

Radiotherapy planning in a prostate cancer phantom model with intraprostatic dominant lesions using stereotactic body radiotherapy with volumetric modulated arcs and a simultaneous integrated boost.

Aim: In the treatment of prostate cancer with radiation therapy, the addition of a simultaneous integrated boost (SIB) to the dominant intraprostatic lesions (DIL) may improve local control. In this study, we aimed to determine the optimal radiation strategy in a phantom model of prostate cancer using volumetric modulated arc therapy for stereotactic body radiotherapy (SBRT-VMAT) with a SIB of 1-4 DILs. Methods: We designed and printed a three-dimensional anthropomorphic phantom pelvis to simulate individual patient structures, including the prostate gland. A total of 36.25 Gy (SBRT) was delivered to the whole prostate. The DILs were irradiated with four different doses (40, 45, 47.5, and 50 Gy) to assess the influence of different SIB doses on dose distribution. The doses were calculated, verified, and measured using both transit and non-transit dosimetry for patient-specific quality assurance using a phantom model. Results: The dose coverage met protocol requirements for all targets. However, the dose was close to violating risk constraints to the rectum when four DILs were treated simultaneously or when the DILs were located in the posterior segments of the prostate. All verification plans passed the assumed tolerance criteria. Conclusions: Moderate dose escalation up to 45 Gy seems appropriate in cases with DILs located in posterior prostate segments or if there are three or more DILs located in other segments.

Biological heterogeneity of primary cancer-associated fibroblasts determines the breast cancer microenvironment.

Cancer-associated fibroblasts are a highly heterogeneous group of cells whose phenotypes and gene alterations are still under deep investigation. As a part of tumor microenvironment, they are the focus of a growing number of studies. Cancer-associated fibroblasts might become a new target of breast cancer therapy, but still more tests and analyses are needed to understand mechanisms and interactions between them and breast cancer cells. The study aimed to isolate cancer associated fibroblasts from breast cancer tissue and to phenotype the isolated cell lines. We focused on various cancer-associated fibroblast characteristic biomarkers and those that might differentiate various cancer-associated fibroblasts' subtypes. Patients with a histological diagnosis of invasive breast cancer (diameter ≤15 mm) and qualified for primary surgical treatment were enrolled in the study. Cell lines were isolated from breast cancer biopsy. For the phenotyping, we used flow cytometry, immunofluorescence and RT-qPCR analysis. Based on our study, there was no indication of a clear pattern in the cancer-associated fibroblasts' classification. Results of cancer-associated fibroblasts expression were highly heterogeneous, and specific subtypes were not defined. Moreover, comparing cancer-associated fibroblasts divided into groups based on BC subtypes from which they were isolated also did not allow to notice of any clear pattern of expressions. In the future, a higher number of analyzed cancer-associated fibroblast cell lines should be investigated to find expression schemes.

FLASH radiotherapy: an emerging approach in radiation therapy.

FLASH radiotherapy (RT) is a technique involving the delivery of ultra-high dose rate radiation to the target. FLASH-RT has been shown to reduce radiation-induced toxicity in healthy tissues without compromising the anti-cancer effects of treatment compared to conventional radiation therapy. In the present article, we review the published data on FLASH-RT and discuss the current state of knowledge of this novel approach. We also highlight the technological constraints and complexity of FLASH-RT and describe the physics underlying this modality, particularly how technology supports energy transfer by ionising radiation (e.g., beam on/off sequence, pulse-energy load, intervals). We emphasise that current preclinical experience is mostly based on FLASH electrons and that clinical application of FLASH-RT is very limited. The incorporation of FLASH-RT into routine clinical radiotherapy will require the development of devices capable of producing FLASH photon beams.

Nontarget and Out-of-Field Doses from Electron Beam Radiotherapy.

In clinical radiotherapy, the most important aspects are the dose distribution in the target volume and healthy organs, including out-of-field doses in the body. Compared to photon beam radiation, dose distribution in electron beam radiotherapy has received much less attention, mainly due to the limited range of electrons in tissues. However, given the growing use of electron intraoperative radiotherapy and FLASH, further study is needed. Therefore, in this study, we determined out-of-field doses from an electron beam in a phantom model using two dosimetric detectors (diode E and cylindrical Farmer-type ionizing chamber) for electron energies of 6 MeV, 9 MeV and 12 MeV. We found a clear decrease in out-of-field doses as the distance from the field edge and depth increased. The out-of-field doses measured with the diode E were lower than those measured with the Farmer-type ionization chamber at each depth and for each electron energy level. The out-of-field doses increased when higher energy megavoltage electron beams were used (except for 9 MeV). The out-of-field doses at shallow depths (1 or 2 cm) declined rapidly up to a distance of 3 cm from the field edge. This study provides valuable data on the deposition of radiation energy from electron beams outside the irradiation field.

Cellular Damage in the Target and Out-Of-Field Peripheral Organs during VMAT SBRT Prostate Radiotherapy: An In Vitro Phantom-Based Study.

Hypo-fractionated stereotactic body radiation therapy (SBRT) is an effective treatment for prostate cancer (PCa). Although many studies have investigated the effects of SBRT on the prostate and adjacent organs, little is known about the effects further out-of-field. The aim of this study was to investigate, both in vitro and in a quasi-humanoid phantom, the biological effects (using a dose-scaling approach) of radiation in the out-of-field peripheral organs delivered by 6 MV volumetric modulated arc therapy (VMAT) SBRT in a prostate cancer model. Healthy prostate cells were irradiated in a phantom at locations corresponding to the prostate, intestine, lung, thyroid, and brain. Seven 10 Gy fractions of VMAT SBRT were delivered to the target in a single session without intermission (scaled-up method). Radiochromic films were used to measure the doses. The radiobiological response was assessed by measuring DNA breaks, the cell survival fraction, and differences in gene expression profile. Our results showed a strong, multiparametric radiobiological response of the cells in the prostate. Outside of the radiation field, the highest doses were observed in the intestine and lung. A small increase (not statistically significant) in DNA damage and cell death was observed in the intestines. Several gene groups (cell cycle, DNA replication) were depleted in the lung and thyroid (DNA replication, endocytosis), but further analysis revealed no changes in the relevant biological processes. This study provides extensive evidence of the types and extent of radiobiological responses during VMAT SBRT in a prostate cancer model. Additional research is needed to determine whether the radiobiological effects observed in the peripheral organs are validated in a clinical context.

Influence of Specific Treatment Parameters on Nontarget and Out-of-Field Doses in a Phantom Model of Prostate SBRT with CyberKnife and TrueBeam.

The aim of the study was to determine the influence of a key treatment plan and beam parameters on overall dose distribution and on doses in organs laying in further distance from the target during prostate SBRT. Multiple representative treatment plans (n = 12) for TrueBeam and CyberKnife were prepared and evaluated. Nontarget doses were measured with anionization chamber, in a quasi-humanoid phantom at four sites corresponding to the intestines, right lung, thyroid, and head. The following parameters were modified: radiotherapy technique, presence or not of a flattening filter, degree of modulation, and use or not of jaw tracking function for TrueBeam and beam orientation set-up, optimization techniques, and number of MUs for CyberKnife. After usual optimization doses in intestines (near the target) were 0.73% and 0.76%, in head (farthest from target) 0.05% and 0.19% for TrueBeam and CyberKnife, respectively. For TrueBeam the highest peripheral (head, thyroid, lung) doses occurred for the VMAT with the flattening filter while the lowest for 3DCRT. For CyberKnife the highest doses were for gantry with caudal direction beams blocked (gantry close to OARs) while the lowest was the low modulated VOLO optimization technique. The easiest method to reduce peripheral doses was to combine FFF with jaw tracking and reducing monitor units at TrueBeam and to avoid gantry position close to OARs together with reduction of monitor units at CyberKnife, respectively. The presented strategies allowed to significantly reduce out-of-field and nontarget doses during prostate radiotherapy delivered with TrueBeam and CyberKnife. A different approach was required to reduce peripheral doses because of the difference in dose delivery techniques: non-coplanar using CyberKnife and coplanar using TrueBeam, respectively.

Does CyberKnife improve dose distribution versus IMRT and VMAT on a linear accelerator in low-risk prostate cancer?

BACKGROUND: Hypofractionated stereotactic body radiation therapy (SBRT) for prostate cancer (PCa) can be delivered with the robot-assisted CyberKnife (CK) system or on a linear accelerator using dynamic intensity-modulated radiotherapy (IMRT) or volumetric arc radiotherapy (VMAT). This retrospective study was performed to determine whether CK offers better dose distribution than IMRT and/or VMAT. MATERIALS AND METHODS: Treatment plans for three techniques were prepared using the same treatment parameters (36.35 Gy, 7.25 Gy/fr). We evaluated target coverage, conformity index (CI), homogeneity index (HI), gamma index (GI), and organs at risk (OAR) constraints. RESULTS: The mean planning target volume (PTV) dose for CK (39.58 Gy) was significantly greater than VMAT or IMRT (both 36.25 Gy). However, CK resulted in a wider dose range (31.48 to 45.89 Gy) vs. VMAT and IMRT (34.6-38.76 Gy). The mean dose to the rectum (V36Gy, mm3) was significantly lower (p < 0.001) in the CK plans (219.78 vs. 519.59 and 422.62, respectively). The mean bladder dose (V37Gy, mm3) was significantly greater for CK (3256 vs. 1090.75 for VMAT and 4.5 for IMRT (p < 0.001). CK yielded significantly better CI (1.07 vs. 1.17 and 1.25 for VMAT and IMRT, respectively; p < 0.01) and HI values (1.27 vs. 1.07 and 1.04; p < 0.01). GI values for the δd = 3mm, δ% = 3% criteria were 99.86 (VMAT), 99.07 (IMRT) and 99.99 (CK). For δd = 2mm, δ% = 2%, the corresponding values were 98.3, 93.35, and 97.12, respectively. CONCLUSIONS: For most variables, CK was superior to both VMAT and IMRT. However, dynamic IMRT techniques, especially VMAT, do not differ significantly from CK plans and are therefore acceptable alternatives to CyberKnife.

Development of a quasi-humanoid phantom to perform dosimetric and radiobiological measurements for out-of-field doses from external beam radiation therapy.

Our understanding of low dose, out-of-field radiation and their radiobiological effects are limited, in part due to the rapid technological advances in external beam radiotherapy, especially for non-coplanar and dynamic techniques. Reliable comparisons of out-of-field doses produced by advanced radiotherapy techniques are difficult due to the limitations of commercially available phantoms. There is a clear need for a functional phantom to accurately measure the dosimetric and radiobiological characteristics of out-of-field doses, which would in turn allow clinicians and medical physicists to optimize treatment parameters. We designed, manufactured, and tested the performance of a quasi-humanoid (Q-H) adult phantom. To test the physics parameters, we used computed tomography (CT) scans of assembled Q-H phantom. Static open field and dynamic techniques were measured both in- and out-of-field with ionization chambers and radiochromic films for two configurations (full solid and with water-filled containers). In the areas simulating soft tissues, lung, and bones, median Hounsfield units and densities were, respectively: 129.8, -738.7, 920.8 HU and 1.110, 0.215, 1.669 g/cm3 . Comparison of the measured to treatment planning systems (TPS) in-field dose values for the sample volumetric arc therapy (VMAT) (6 MV flattening filter-free (FFF)) plan, 96.4% of analyzed points passed the gamma evaluation criteria (L2%/2 mm, threshold (TH) 10%) and less than 1.50% for point dose verification. In the two phantom configurations: full poly(methyl) methacrylate (PMMA) and with water container, the off-axis median doses for open field, relative to the central axis of the beam (CAX) were similar, respectively: 0.900% versus 0.907% (15 cm distance to CAX); 0.096% versus 0.120% (35 cm); 0.018% versus 0.018% (52 cm); 0.009% versus 0.008% (74 cm). For VMAT 6 MV FFF, doses relative the CAX were, respectively: 0.667% (15 cm), 0.062% (35 cm), 0.019% (52 cm), 0.016% (74 cm). The Q-H phantom meets the International Commission on Radiation Units and Measurements (ICRU) and American Association of Physicists in Medicine (AAPM) recommended phantom criteria, providing medical physicists with a reliable, comprehensive system to perform dose calculation and measurements and to assess the impact on radiobiological response and on the risk of secondary tumor induction.

The impact of different optimization strategies on the agreement between planned and delivered doses during volumetric modulated arc therapy for total marrow irradiation.

AIM OF THE STUDY: To evaluate the agreement between planned and delivered doses and its potential correlation with the plans' complexity subjected to dosimetric verification. MATERIAL AND METHODS: Four isocentre volumetric modulated arc therapy for total marrow irradiation plans optimized simultaneously with (P1) and without (P2) MU reduction were evaluated dosimetrically by γ method performed in a global mode for 4 combinations of γ-index criteria (2%/2 mm, 2%/3 mm, 3%/2 mm, and 3%/3 mm). The evaluation was conducted for 4 regions (head and neck, chest, abdomen and upper pelvis, and lower pelvis and thighs) that were determined geometrically by the isocentres. The Wilcoxon test was used to detect significant differences between γ passing rate (GPR) analysis results for the P1 and P2 plans. The Pearson correlation was used to check the relationship between GPR and the plans' complexity. RESULTS: Except for the head and neck region, the P2 plans had better GPRs than the P1 plans. Only for hard combinations of γ-index criteria (i.e. 2%/3 mm, 2%/2 mm) were the GPRs differences between P1 and P2 clinically meaningful, and they were detected in the chest, abdomen and upper pelvis, and lower pelvis and thighs regions. The highest correlations between GPR and the indices describing the plans' complexity were found for the chest region. No correlation was found for the head and neck region. CONCLUSIONS: The P2 plans showed better agreement between planned and delivered doses compared to the P1 plans. The GPR and the plans' complexity depend on the anatomy region and are most important for the chest region.

Results of the IROCA international clinical audit in prostate cancer radiotherapy at six comprehensive cancer centres.

To assess adherence to standard clinical practice for the diagnosis and treatment of patients undergoing prostate cancer (PCa) radiotherapy in four European countries using clinical audits as part of the international IROCA project. Multi-institutional, retrospective cohort study of 240 randomly-selected patients treated for PCa (n = 40/centre) in the year 2015 at six European hospitals. Clinical indicators applicable to general and PCa-specific radiotherapy processes were evaluated. All data were obtained directly from medical records. The audits were performed in the year 2017. Adherence to clinical protocols and practices was satisfactory, but with substantial inter-centre variability in numerous variables, as follows: staging MRI (range 27.5-87.5% of cases); presentation to multidisciplinary tumour board (2.5-100%); time elapsed between initial visit to the radiation oncology department and treatment initiation (42-102.5 days); number of treatment interruptions ≥ 1 day (7.5-97.5%). The most common deviation from standard clinical practice was inconsistent data registration, mainly failure to report data related to diagnosis, treatment, and/or adverse events. This clinical audit detected substantial inter-centre variability in adherence to standard clinical practice, most notably inconsistent record keeping. These findings confirm the value of performing clinical audits to detect deviations from standard clinical practices and procedures.

Ionizing radiation exposure of stem cell-derived chondrocytes affects their gene and microRNA expression profiles and cytokine production.

Human induced pluripotent stem cells (hiPSCs) can be differentiated into chondrocyte-like cells. However, implantation of these cells is not without risk given that those transplanted cells may one day undergo ionizing radiation (IR) in patients who develop cancer. We aimed to evaluate the effect of IR on chondrocyte-like cells differentiated from hiPSCs by determining their gene and microRNA expression profile and proteomic analysis. Chondrocyte-like cells differentiated from hiPSCs were placed in a purpose-designed phantom to model laryngeal cancer and irradiated with 1, 2, or 3 Gy. High-throughput analyses were performed to determine the gene and microRNA expression profile based on microarrays. The composition of the medium was also analyzed. The following essential biological processes were activated in these hiPSC-derived chondrocytes after IR: "apoptotic process", "cellular response to DNA damage stimulus", and "regulation of programmed cell death". These findings show the microRNAs that are primarily responsible for controlling the genes of the biological processes described above. We also detected changes in the secretion level of specific cytokines. This study demonstrates that IR activates DNA damage response mechanisms in differentiated cells and that the level of activation is a function of the radiation dose.

Verification of electron beam parameters in an intraoperative linear accelerator using dosimetric and radiobiological response methods.

BACKGROUND: The availability of linear accelerators (linac) for research purposes is often limited and therefore alternative radiation sources are needed to conduct radiobiological research. The National Centre for Radiation Research in Poland recently developed an intraoperative mobile linac that enables electron irradiation at energies ranging from 4 to 12 MeV and dose rates of 5 or 10 Gy/min. The present study was conducted to evaluate the electron beam parameters of this intraoperative linac and to verify the set-up to evaluate out-of-field doses in a water phantom, which were determined through dosimetric and biological response measurements. MATERIALS AND METHODS: The distribution of radiation doses along and across the radiation beam were measured in a water phantom using a semiconductor detector and absolute doses using an ionisation chamber. Two luminal breast cancer cell lines (T-47D and HER2 positive SK-BR-3) were placed in the phantom to study radiation response at doses ranging from 2 to 10 Gy. Cell response was measured by clonogenic assays. RESULTS AND CONCLUSION: The electron beam properties, including depth doses and profiles, were within expected range for the stated energies. These results confirm the viability of this device and set-up as a source of megavoltage electrons to evaluate the radiobiological response of tumour cells.

Currently used in clinical practice beam rate changes have no significant effect on the reduction of clonogenic capacity of PNT1A cells in vitro.

BACKGROUND: Due to the lack of selectivity of ionizing radiation between normal and cancer cells, it is important to improve the existing radiation patterns. Lowering the risk of cancer recurrence and comfort during treatment are priorities in radiotherapy. MATERIALS AND METHODS: In the experiment we used dose verification to determine the irradiation time calculated by a treatment planning system for 6XFFF and 10XFFF beams. Cells cultured under standard conditions were irradiated with a dose of 2 Gy at different beam rates 400 MU/min, 600 MU/min, 800 MU/min, 1000 MU/min, 1400 MU/min, 1600 MU/min and 2400 MU/min using 6XFFF, 10XFFF and 6XFF beams. RESULTS: The experiment was aimed at comparing the biological response of normal prostate cells after clinically applied radiation patterns. No statistically significant differences in the cellular response were observed. The wide range of beam rates as well as the beam profiles did not significantly affect cell proliferation. CONCLUSIONS: High beam rates, without significantly affecting the clonogenic capacity of cells, have an impact on the quality of patient's treatment. With the increasing beam rate the irradiation time is shortened, which has an important impact on patients' health. This experiment can have a practical significance.

Multicentre clinical radiotherapy audit in rectal cancer: results of the IROCA project.

PURPOSE: To perform a clinical audit to assess adherence to standard clinical practice for the diagnosis, treatment, and follow-up of patients undergoing radiotherapy for rectal cancer treatment in four European countries. MATERIALS AND METHODS: Multi-institutional, retrospective cohort study of 221 patients treated for rectal cancer in 2015 at six European cancer centres. Clinical indicators applicable to general radiotherapy processes were evaluated. All data were obtained from electronic medical records. RESULTS: The audits were performed in the year 2017. We found substantial inter-centre variability in adherence to standard clinical practices: 1) presentation of cases at departmental clinical sessions (range, 0-100%) or multidisciplinary tumour board (50-95%); 2) pretreatment MRI (61.5-100%) and thoracoabdominal CT (15.0-100%). Large inter-centre differences were observed in the mean interval between biopsy and first visit to the radiotherapy department (range, 21.6-58.6 days) and between the first visit and start of treatment (15.1-38.8 days). Treatment interruptions ≥ 1 day occurred in 43.9% (2.5-90%) of cases overall. Treatment compensation was performed in 2.1% of cases. Treatment was completed in the prescribed time in 55.7% of cases. CONCLUSIONS: This multi-institutional clinical audit revealed that most centres adhered to standard clinical practices for most of the radiotherapy processes-related variables assessed. However, the audit revealed marked inter-centre variability for certain quality indicators, particularly inconsistent record keeping. Multiple targets for improvement and/or harmonisation were identified, confirming the value of routine clinical audits to detect potential deviations from standard clinical practice.

Software simulation of tumour motion dose effects during flattened and unflattened ITV-based VMAT lung SBRT.

PURPOSE: Restricted studies comparing different dose rate parameters are available while ITV-based VMAT lung SBRT planning leads to perform the analysis of the most suitable parameters of the external beams used. The special emphasis was placed on the impact of dose rate on dose distribution variations in target volumes due to interplay effects. METHODS: Four VMAT plans were calculated for 15 lung tumours using 6 MV photon beam quality (flattening filter FF vs. flattening filter free FFF beams) and maximum dose rate of 600 MU/min, 1000 MU/min and 1400 MU/min. Three kinds of motion simulations were performed finally giving 180 plans with perturbed dose distributions. RESULTS: 6FFF-1400 MUs/min plans were characterized by the shortest beam on time (1.8 ±â€¯0.2 min). Analysing the performed motion simulation results, the mean dose (Dmean) is not a sensitive parameter to related interplay effects. Looking for local maximum and local minimum doses, some discrepancies were found, but their significance was presented for individual patients, not for the whole cohort. The same was observed for other verified dose metrics. CONCLUSIONS: Generally, the evaluation of VMAT robustness between FF and FFF concepts against interplay effect showed a negligible effect of simulated motion influence on tumour coverage among different photon beam quality parameters. Due to the lack of FFF beams, smaller radiotherapy centres are able to perform ITV-based VMAT lung SBRT treatment in a safe way. Radiotherapy department having FFF beams could perform safe, fast and efficient ITV-based VMAT lung SBRT without a concern about significance of interplay effects.

Impact of different optimization strategies on the compatibility between planned and delivered doses during radiation therapy of cervical cancer.

PURPOSE: To analyse the impact of different optimization strategies on the compatibility between planned and delivered doses during radiotherapy of cervical cancer. MATERIAL/METHODS: Four treatment plans differing in optimisation strategies were prepared for ten cervical cancer cases. These were: volumetric modulated arc therapy with (_OPT) and without optimization of the doses in the bone marrow and for two sets of margins applied to the clinical target volume that arose from image guidance based on the bones (IG(B)) and soft tissues (IG(ST)). The plans were subjected to dosimetric verification by using the ArcCHECK system and 3DVH software. The planned dose distributions were compared with the corresponding measured dose distributions in the light of complexity of the plans and its deliverability. RESULTS: The clinically significant impact of the plans complexity on their deliverability is visible only for the gamma passing rates analysis performed in a local mode and directly in the organs. While more general analyses show statistically significant differences, the clinical relevance of them has not been confirmed. The analysis showed that IG(ST)_OPT and IG(B)_OPT significantly differ from IG(ST) and IG(B). The clinical acceptance of IG(ST)_OPT obtained for hard combinations of gamma acceptance criteria (2%/2 mm) confirm its satisfactory deliverability. In turn, for IG(B)_OPT in the case of the rectum, the combination of 2%/2 mm did not meet the criteria of acceptance. CONCLUSION: Despite the complexity of the IG(ST)_OPT, the results of analysis confirm the acceptance of its deliverability when 2%/2 mm gamma acceptance criteria are used during the analysis.

EPID-based daily verification of reproducibility of patients' irradiation with IMRT plans.

AIM: The aim of the work was to catch potential errors with daily EPID measurements of repeatability of the dose distribution during irradiation of IMRT patients. MATERIALS AND METHODS: In the first stage, measurements were made using an anthropomorphic phantom in which the method of collecting data with an EPID device and the possibility of detecting errors in positioning were developed. Next, for 23 patients, the pelvis (P) and head and neck (H&N) regions, images were collected with an EPID device for each IMRT subfield daily and compared to reference images using the gamma method (DTA 3 mm, DD 3%). Finally, the dependencies between treatment plan parameters, pre-verification results and repeatability of collected images were evaluated. RESULTS: The anthropomorphic phantom study has shown what kind of effects we can expect with EPID measured at potential shifts during radiotherapy. For the clinical case, score results were obtained for individual tumor regions as below: (P) 0.786 ± 1.046, (H&N) 0.720 ± 1.552. For most evaluated cases, score values were below 1%: (P) 75.5% and (H&N) 83.9% of analyzed fields. 95% of all evaluated data was with the score below: (P) 2.86% and (H&N) 3.40%. The relationship between the results of the analysis of daily collected images and the results of pre-verification, field size and irradiation time was shown. CONCLUSIONS: The EPID-based daily verification can provide extra information about day-to-day repeatability of treatment, without additional dose.

Different levels of let-7d expression modulate response of FaDu cells to irradiation and chemotherapeutics.

The implication of the let-7 family in cancer development is multifaceted. The family acts as tumor suppressor miRNA although overexpression of let-7 has also been described in many types of cancer, including head and neck squamous cell carcinoma (HNSCC). The aim of this study includes whether different expression levels of let-7d has an influence on chemo- and radiosensitivity. FaDu cell line models with a gradually increased level of let-7d (models from A to E) were generated with the lentiviral system. Expression levels of pluripotency, chemo-radioresistance/apoptosis, and targets of mRNAs were analyzed by real-time reverse transcription-PCR (qRT-PCR). Radiosensitivity was analyzed using a clonogenic assay after irradiation. Response to cisplatin, 5-FU, doxorubicin, and paclitaxel was done with MTT assay. Statistically significant decrease of K-RAS (p = 0.0369) and CASPASE3 (p = 0.0342) were observed with the growing expression level of let-7d. Cisplatin, 5-FU and doxorubicin caused similar decreased of cell survival with the increase of let-7d level (p = 0.004, post-trend p = 0.046; p = 0.004, post trend p = 0.0005 and p<0.0001, post trend p = 0.0001, respectively). All models were resistant to paclitaxel, irrespective of let-7d expression levels. Only two of the generated models (A and C) were radiosensitive (p = 0.0002). CONCLUSION: the above results indicated that the level of let-7d expression is an important factor for cell response to irradiation and chemotherapeutics.

Carcinogenesis Induced by Low-dose Radiation.

BACKGROUND: Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure. CONCLUSIONS: Understanding the molecular mechanisms of response to low dose radiation is crucial for the proper evaluation of risks and benefits that stem from these exposures and should be considered in the radiotherapy treatment planning and in determining the allowed occupational exposures.