High-dose Irradiation Stimulated Breast Tumor Microenvironment to Enhance Tumor Cell Growth and Decrease Tumor Cell Motility

Background: Surgery and radiotherapy are two main modalities of breast cancer treatment. However, surgery affects the tumor microenvironment negatively and promotes the growth of possible malignant cells remaining in the tumor bed. Objective: The present study aimed to investigate the effects of intraoperative radiotherapy (IORT) on the tumor microenvironment. Therefore, the effect of surgical wound fluid (WF), collected from operated and irradiated patients on the growth and motility of a breast cancer cell line (MCF-7) was assessed. Material and Methods: In this experimental study, preoperative blood serum (PS) and secreted WF from 18 patients who underwent breast-conserving surgery (IORT-) and 19 patients who received IORT following surgery (IORT+) were collected. The samples were purified and added to MCF-7 cultures. Two groups of the cells were treated with and without fetal bovine serum (FBS) and used as positive and negative controls. Applying 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch wound healing assays, the growth and motility of MCF-7 cells were measured. Results: Cell growth of the cells receiving WF from IORT+ patients (WF+) was statistically higher than the corresponding values of the cells received PS or WF from IORT- patients (WF-) (P<0.01). Both WF+ and WF- decreased the cells’ migration ability compared to PS (P<0.02) and FBS (P<0.002), although WF+ caused a more significant reduction (P<0.02).  Conclusion: Wound fluid extracted from breast cancer patients who underwent both surgery and IORT increased the growth of breast tumor cells, but decreased their ability to migrate

Evaluation of Dose Calculation Accuracy of Isogray Treatment Planning System in Craniospinal Radiotherapy

Introduction: Craniospinal radiotherapy is a therapeutic technique for central nervous system (CNS) tumors, which requires meticulous attention to technique and dosimetry.Treatment planning system (TPS) is one of the main equipment in radiotherapy; therefore, the evaluation of its accuracy is essential for dose calculation. The present study evaluates the validity of Isogray TPS in craniospinal irradiation techniques. Material and Methods: The computed tomography (CT) images of the brain and spine of the Rando phantom were acquired. Two techniques were designed. In technique 1, the whole CNS was irradiated with 6 MV photon beam. In technique 2, the brain and spine were irradiated with 6 MV photon and 18 MeV electron beam, respectively. The tumor and organs at risk doses were measured by thermoluminescent dosimeter (TLD). In addition, photon and electron dose measurements inside and outside the treatment field were accomplished using TLD, and then compared to the corresponding values calculated by TPS. Results: According to the results, in both electron and photon beams, the differences between the doses calculated by TLD and TPS for the points inside the treatment field were less than 4% for 90% of the measurement points. However, for the points outside the treatment field borders, the differences ranged within 10-40%. These differences were indicative of the sufficient dosimetric accuracy of Isogray TPS. Conclusion: The comparison of dosimetry results with those of TPS results revealed the accuracy of Isogray TPS. In both techniques, the maximum difference between the TLD- and TPS-measured doses was observed in the mandible

Preliminary Results of the Effects of Localized High-Dose Radiotherapy Combined with Total Body Low-Dose Irradiation on Tumor Growth and Stimulating the Immune System in Tumor-Bearing Mice

Background: The immune system plays an extensive role in eliminating tumor cells. On the other hand, low-dose irradiation stimulates the immune system.Objective: The present study aimed to investigate the therapeutic outcomes of localized high-dose radiotherapy (LH) alone and combined with total body low-dose irradiation (TB).Material and Methods: In this experimental study, B16F0 tumor cells were injected into the right flank of C57JL/6 mice. The mice were treated with LH alone (13 Gy X-rays to the tumor surface) (LH group) or combined with TB (85 mGy X-rays at the skin) (TB+LH group). Then the tumor volume, the mice’s lifespan, the number of lymphocytes extracted from the spleen, and interferon gamma (IFN-γ) production were measured.Results: Reduced number of lymphocytes, compared to non-irradiated mice (control group), was observed in LH and TB+LH groups. However, the identical number of cultured lymphocytes produced a higher level of IFN-γ in irradiated groups. Comparing the irradiated groups, the number of lymphocytes and their IFN-γ production, tumor growth control, and the mice’s lifespan were statistically higher in TB+LH group. Conclusion: Observing a higher level of IFN-γ in TB+LH group compared to LH group indicates that low-dose radiation enhanced the stimulating effects of high-dose radiation on the immune system. It caused the mice in TB+LH group to have a more prolonged lifespan and a lower tumor growth rate. Therefore, it is worth our attention for future studies to investigate whether total body low-dose irradiation can be utilized before radiotherapy to enhance its efficiency

Evaluation of dose calculations accuracy of a commercial treatment planning system for the head and neck region in radiotherapy

AimThe objective was to quantify dose calculation accuracy of TiGRT TPS for head and neck region in radiotherapy.BackgroundIn radiotherapy of head and neck cancers, treatment planning is difficult, due to the complex shape of target volumes and also to spare critical and normal structures. These organs are often very near to the target volumes and have low tolerance to radiation. In this regard, dose calculation accuracy of treatment planning system (TPS) must be high enough.Materials and methodsThermoluminescent dosimeter-100 (TLD-100) chips were used within RANDO phantom for dose measurement. TiGRT TPS was also applied for dose calculation. Finally, difference between measured doses (Dmeas) and calculated doses (Dcalc) was obtained to quantify the dose calculation accuracy of the TPS at head and neck region.ResultsFor in-field regions, in some points, the TiGRT TPS overestimated the dose compared to the measurements and for other points underestimated the dose. For outside field regions, the TiGRT TPS underestimated the dose compared to the measurements. For most points, the difference values between Dcalc and Dmeas for the in-field and outside field regions were less than 5% and 40%, respectively.ConclusionsDue to the sensitive structures to radiation in the head and neck region, the dose calculation accuracy of TPSs should be sufficient. According to the results of this study, it is concluded that the accuracy of dose calculation of TiGRT TPS is enough for in-field and out of field regions

Assessment of Dose Calculation Accuracy of TiGRT Treatment Planning System for Physical Wedged fields in Radiotherapy

Introduction Wedge modifiers are commonly applied in external beam radiotherapy to change the dose distribution corresponding to the body contour and to obtain a uniform dose distribution within the target volume. Since the radiation dose delivered to the target must be within ±5% of the prescribed dose, accurate dose calculation by a treatment planning system (TPS) is important. The objective of the present study was to quantify the dose calculation accuracy of TiGRT TPS for physical wedged fields in radiotherapy. Materials and Methods A Semiflex™ ionization chamber was used for dose measurements in a water phantom; TiGRT TPS was also applied for dose calculations. The central axis (i.e., high dose-small dose gradient), build-up (i.e., high dose-large dose gradient), off-axis (i.e., high dose-small dose gradient), and out-of-field (i.e., low dose-small dose gradient) regions were evaluated in this study. Finally, the confidence limit values were obtained to quantify the dose calculation accuracy of TPS in these regions. Results The confidence limit values for the central axis, build-up, off-axis, and out-of-field regions were 1.01, 8.62, 1.79, and 55.24, respectively. Furthermore, the results showed that TiGRT TPS underestimated the dose of build-up and out-of-field regions for most points. Conclusion According to the results of the present study, it can be concluded that the dose calculation accuracy of TiGRT TPS for physical wedged fields in the central axis, build-up, and off-axis regions is adequate, while it is insufficient for out-of-field regions

Assessment of the accuracy of dose calculation in the build-up region of the tangential field of the breast for a radiotherapy treatment planning system

Aim of the study : Our objective was to quantify the accuracy of dose calculation in the build-up region of the tangential field of the breast for a TiGRT treatment planning system (TPS). Material and methods : Thermoluminescent dosimeter (TLD) chips were arranged in a RANDO phantom for the dose measurement. TiGRT TPS was also used for the dose calculation. Finally, confidence limit values were obtained to quantify the accuracy of the dose calculation of the TPS at the build-up region. Results : In the open field, for gantry angles of 15°, 30°, and 60°, the confidence limit values were 17.68, 19.97, and 34.62 at a depth of 5 mm, and 24.01, 19.07, and 15.74 at a depth of 15 mm, respectively. In the wedge field, for gantry angles of 15°, 30°, and 60°, the confidence limit values were 21.64, 26.80, and 34.87 at a depth of 5 mm, and 27.92, 22.04, and 20.03 at a depth of 15 mm, respectively. Additionally, the findings showed that at a depth of 5 mm, the confidence limit values increased with increasing gantry angle while at a depth of 15 mm, the confidence limit values decreased with increasing gantry angle. Conclusions : Overall, TiGRT TPS overestimated doses compared to TLD measurements, and the confidence limit values were greater for the wedge field than for the open fields. Our findings suggest that the assessment of dose distributions in large-dose gradient regions (i.e. build-up region) should not entirely rely on TPS calculations

Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study

Objective: Radiation effects induced in non-irradiated cells are termed radiation-induced bystander effects (RIBE). The present study intends to examine the RIBE response of QU-DB bystander cells to first, second and third radiation fractions and compare their cumulative outcome with an equal, single acute dose. Materials and Methods: This experimental study irradiated three groups of target cells for one, two and three times with 60Co gamma rays. One hour after irradiation, we transferred their culture media to non-irradiated (bystander) cells. We used the cytokinesis block micronucleus assay to evaluate RIBE response in the bystander cells. The numbers of micronuclei generated in bystander cells were determined. Results: RIBE response to single acute doses increased up to 4 Gy, then decreased, and finally at the 8 Gy dose disappeared. The second and third fractions induced RIBE in bystander cells, except when RIBE reached to the maximum level at the first fraction. We split the 4 Gy acute dose into two fractions, which decreased the RIBE response. However, fractionation of 6 Gy (into two fractions of 3 Gy or three fractions of 2 Gy) had no effect on RIBE response. When we split the 8 Gy acute dose into two fractions we observed RIBE, which had disappeared following the single 8 Gy dose. Conclusion: The impact of dose fractionation on RIBE induced in QU-DB cells depended on the RIBE dose-response relationship. Where RIBE increased proportionally with the dose, fractionation reduced the RIBE response. In contrast, at high doses where RIBE decreased proportionally with the dose, fractionation either did not change RIBE (at 6 Gy) or increased it (at 8 Gy)

Investigation of the bystander effect in MRC5 cells after acute and fractionated irradiation in vitro

Radiation-induced bystander effect (RIBE) has been defined as radiation responses observed in nonirradiated cells. It has been the focus of investigators worldwide due to the deleterious effects it induces in nonirradiated cells. The present study was performed to investigate whether acute or fractionated irradiation will evoke a differential bystander response in MRC5 cells. A normal human cell line (MRC5), and a human lung tumor cell line (QU-DB) were exposed to 0, 1, 2, and 4Gy of single acute or fractionated irradiation of equal fractions with a gap of 6 h. The MRC5 cells were supplemented with the media of irradiated cells and their micronucleus frequency was determined. The micronucleus frequency after single and fractionated irradiation did not vary significantly in the MRC5 cells conditioned with autologous or QU-DB cell-irradiated media, except for 4Gy where the frequency of micronucleated cells was lower in those MRC5 cells cultured in the media of QU-DB-exposed with a single dose of 4Gy. Our study demonstrates that the radiation-induced bystander effect was almost similar after single acute and fractionated exposure in MRC5 cells