The impact of margin reduction on radiation dose distribution of ultra-hypofractionated prostate radiotherapy utilizing a 1.5-T MR-Linac.

BACKGROUND: We examined the effects of reducing the planning target volume (PTV) margin in MR-guided radiotherapy (MRgRT) on the distribution of radiation dose to target volumes and organs-at-risk (OARs). Thus, we compared MR-Linac (MRL) plans with and without reduced margin and intensity-modulated radiotherapy (IMRT) plan with conventional linac for low-risk prostate cancer patients receiving 36.25 Gy in five fractions of ultra-hypofractionated radiation therapy. MATERIALS AND METHODS: Twenty low-risk prostate cancer patients treated with 1.5 T MR-Linac were evaluated. The same planning CT images were used for four plans: the MRL-R plan with reduced margin planning target volume (PTV-R) and the MRL-N plan with normal margin PTV (PTV-N), which is also used for IMRT plan. In four plans, PTV doses, organs-at-risk (OARs) doses, the homogeneity index (HI), and monitor units were compared. RESULTS: All plans met the criteria for PTV coverage and OARs dose constraints. The maximum and mean PTV doses were significantly higher in the MRL-R and MRL-N plans compared to the IMRT plan. The HI was lowest in the IMRT plan (0.040 ± 0.013) and highest in the MRL-N plan (0.055 ± 0.012; p < 0.001). There was no significant difference in the PTV dosimetric parameters between the MRL-R and the MRL-N plans. The high doses in the rectum was significantly lower in the MRL-R compared to other plans. The bladder V36.25 Gy was significantly lower in the MRL-R plan (2.43 ± 1.87 Gy) compared to MRL-N (4.50 ± 2.42 Gy; p < 0.001), and IMRT plans (4.76 ± 2.77 Gy; p < 0.001). There was no significant difference in the low-dose volumes of the body, maximum femur doses, or monitor units across each plan. CONCLUSIONS: Ultra-hypofractionated MR-guided RT with 1.5 T MRL is dosimetrically feasible for patients with prostate cancer. The improved soft tissue contrast and the online adaptive plan for 1.5 T MR-Linac allows for PTV margin reduction resulted in a significant dose reduction in OARs.

Cardiac angiosarcoma treated with 1.5 Tesla MR-guided adaptive stereotactic body radiotherapy - Case report and review of the literature.

INTRODUCTION: Cardiac angiosarcoma is a very rare disease. As a result of their nonspecific presentation symptoms, and the lack of consensus in treatment, caution should be taken in both diagnosis and treatment. The role of radiotherapy (RT) is debatable due to the continuous movement of the heart, which makes it difficult to safely deliver high radiation doses to the target volume. PRESENTATION OF CASE: The case of a 16-year-old boy with cardiac angiosarcoma that recurred one year after surgery and was treated with chemotherapy is presented. The patient received high field 1.5-Tesla (magnetic resonance) MR-Linac treatment in 5 fractions with a dosage of 25 Gy to the tumor bed and 30 Gy to the recurrent nodules using the simultaneous integrated boost technique. The patient tolerated the treatment well and had stable disease two months later. DISCUSSION: MR-guided radiotherapy, particularly in the case of cardiac malignancies, allows for direct tumor visualization with high soft tissue image resolution capacity. Furthermore, modern RT techniques allow for the full therapeutic window to be used by achieving superior dose distributions, allowing for dose escalation strategies with tolerable toxicity rates. CONCLUSION: Magnetic resonance guided RT allows direct visualization of the target during treatment delivery, allowing for higher-dose administration with less damage to healthy tissue near the tumor. This treatment strategy is a viable option in selected patients with cardiac angiosarcoma.

Dosimetric Comparison of Sequential Versus Simultaneous-integrated Boost in Early-stage Breast Cancer Patients Treated With Breast-conserving Surgery.

BACKGROUND/AIM: To compare simultaneous-integrated boost (SIB) versus sequential-boost (SB) delivered in the context of whole-breast irradiation (WBI) via volumetric-modulated arc therapy (VMAT) and helical-tomotherapy (HT). MATERIALS AND METHODS: Planning target-volume (PTV) dosimetric parameters and organs at risk (OAR) were analyzed for SB plan (50 Gy plus 16 Gy boost) and SIB plan (50.4 Gy WBI and 64.4 Gy tumor bed boost) in VMAT and HT techniques. RESULTS: Conformity and homogeneity for target-volume doses were better in HT plans compared to VMAT plans. There were no significant differences in ipsilateral lung doses between VMAT and HT plans for SB/SIB techniques, except for a significantly higher lung V5 value with VMAT-SB, and lung V13 value with HT-SIB technique. HT provided a statistically significant decrease in contralateral lung mean V5. CONCLUSION: The SIB technique showed better target-volume dose distribution in both HT and VMAT plans, and better sparing heart in HT compared to the SB technique.

Tubulin-binding anticancer polysulfides induce cell death via mitotic arrest and autophagic interference in colorectal cancer.

Polysulfanes show chemopreventive effects against gastrointestinal tumors. We identified diallyl tetrasulfide and its derivative, dibenzyl tetrasulfide (DBTTS), to be mitotic inhibitors and apoptosis inducers. Here, we translate their application in colorectal cancer (CRC). MALDI-TOF-MS analysis identified both compounds as reversible tubulin binders, validated by in cellulo α-tubulin degradation. BRAF(V600E)-mutated HT-29 cells were resistant to DBTTS, as evidenced by mitotic arrest for 48 h prior to apoptosis induction compared to KRAS(G12V)-mutated SW480/620 cells, which committed to death earlier. The prolonged mitotic block correlated with autophagy impairment and p62 protein accumulation in HT-29 but not in SW480/620 cells, whereas siRNA-mediated p62 inhibition sensitized HT-29 cells to death. In silico analysis with 484 colorectal cancer patients associated higher p62 expression and reduced autophagic flux with greater overall survival. Accordingly, we hypothesized that DBTTS targets CRC survival/death through autophagy interference in cell types with differential autophagic capacities. We confirmed the therapeutic potential of DBTTS by the inhibition of spheroid and colony formation capacities in CRC cells, as well as in HT-29 zebrafish xenografts in vivo.

Dosimetric analysis of testicular doses in prostate intensity-modulated and volumetric-modulated arc radiation therapy at different energy levels.

The aim of this study is to evaluate the incidental testicular doses during prostate radiation therapy with intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) at different energies. Dosimetric data of 15 patients with intermediate-risk prostate cancer who were treated with radiotherapy were analyzed. The prescribed dose was 78Gy in 39 fractions. Dosimetric analysis compared testicular doses generated by 7-field intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy with a single arc at 6, 10, and 15MV energy levels. Testicular doses calculated from the treatment planning system and doses measured from the detectors were analyzed. Mean testicular doses from the intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy per fraction calculated in the treatment planning system were 16.3 ± 10.3cGy vs 21.5 ± 11.2cGy (p = 0.03) at 6MV, 13.4 ± 10.4cGy vs 17.8 ± 10.7cGy (p = 0.04) at 10MV, and 10.6 ± 8.5cGy vs 14.5 ± 8.6cGy (p = 0.03) at 15MV, respectively. Mean scattered testicular doses in the phantom measurements were 99.5 ± 17.2cGy, 118.7 ± 16.4cGy, and 193.9 ± 14.5cGy at 6, 10, and 15MV, respectively, in the intensity-modulated radiotherapy plans. In the volumetric-modulated arc radiotherapy plans, corresponding testicular doses per course were 90.4 ± 16.3cGy, 103.6 ± 16.4cGy, and 139.3 ± 14.6cGy at 6, 10, and 15MV, respectively. In conclusions, this study was the first to measure the incidental testicular doses by intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy plans at different energy levels during prostate-only irradiation. Higher photon energy and volumetric-modulated arc radiotherapy plans resulted in higher incidental testicular doses compared with lower photon energy and intensity-modulated radiotherapy plans.

Correlation of conventional and conformal plan parameters for predicting radiation pneumonitis in patients treated with breast cancer.

PURPOSE: The purpose of this study is to evaluate the correlation between the conventional plan parameters and dosimetric parameters obtained from conformal radiotherapy (RT) planning, and between these parameters and radiation pneumontitis (RP) incidence. METHODS: Clinical and dosimetric data of 122 patients that were treated with mastectomy and adjuvant 3D conformal RT (39% received 2-field RT [2-FRT], and in addition, 61% received 4-field RT [4-FRT]) were retrospectively analyzed. Central lung depth (CLD), maximum lung depth (MLD), and lung length were measured by the conventional plan. Lung dose-volume histograms (DVH) were created with conformal planning, and the lung volumes receiving 5 to 50 Gy (V(5Gy) to V(50Gy)) were calculated. Minimum (D(min)), maximum (D(max)), and mean doses (D(mean)) for the ipsilateral lung and bilateral lungs were measured by DVH. Correlations between 3D dosimetric data and 2D radiographic parameters were analyzed. RESULTS: The conventional plan parameters did not significantly differ between 2-FRT and 4-FRT. The conformal plan D(min), D(max), and D(mean) values were higher in 4-FRT versus 2-FRT. CLD and MLD were correlated with DVH parameter V(5Gy) to V(45Gy) values for ipsilateral, as well as bilateral lungs for 2-FRT. MLD and ipsilateral D(mean) via 2-FRT planning had the strongest positive correlation (r=0.76, p<0.01). Moderate correlations existed between CLD and ipsilateral and bilateral lung V(5Gy-45Gy), and between MLD and bilateral lung V(5Gy-45Gy) values in 2-FRT. Only four patients developed symptomatic RP, 4 with 4-FRT and one with 2-FRT. CONCLUSION: The conformal plan parameters were strongly correlated with dose-volume parameters for breast 2-FRT. With only 4 cases of Grade 3 RP observed, our study is limited in its ability to provide definitive guidance, however assuming that CLD is an indicator for RP, V(20Gy) could be used as a predictor for RP and for 2-FRT. A well-defined parameters are still required to predict RP in 4-FRT.

Effect of different prosthetic materials on radiation dose distribution in an orbital defect: a clinical report.

It is challenging to treat and irradiate empty cavities with external-beam radiation therapy (EBRT) because body contour irregularities can result in dose heterogeneities. The use of compensator materials to fill the empty cavities can provide a more homogeneous radiation dose distribution. The purposes of this clinical report are to describe the use of 3 different materials (elastomeric material, water-filled balloon, and acrylic resin) in an orbital defect and compare the dosimetric parameters and photon-electron dose distribution during EBRT.

Evaluation of field-in-field technique for total body irradiation.

PURPOSE: To evaluate the clinical use of a field-in-field (FIF) technique for total body irradiation (TBI) using a treatment-planning system (TPS) and to verify TPS results with in vivo dose measurements using metal-oxide-semiconductor field-effect transistor (MOSFET) detectors. METHODS AND MATERIALS: Clinical and dosimetric data of 10 patients treated with TBI were assessed. Certain radiation parameters were measured using homogenous and regular phantoms at an extended distance of 380 cm, and the results were compared with data from a conventional standard distance of 100 cm. Additionally, dosimetric validation of TPS doses was performed with a Rando phantom using manual calculations. A three-dimensional computed tomography plan was generated involving 18-MV photon beams with a TPS for both open-field and FIF techniques. The midline doses were measured at the head, neck, lung, umbilicus, and pelvis for both open-field and FIF techniques. RESULTS: All patients received planned TBI using the FIF technique with 18-MV photon energies and 2 Gy b.i.d. on 3 consecutive days. The difference in tissue maximum ratios between the extended and conventional distances was <2%. The mean deviation of manual calculations compared with TPS data was +1.6% (range, 0.1-2.4%). A homogenous dose distribution was obtained with 18-MV photon beams using the FIF technique. The mean lung dose for the FIF technique was 79.2% (9.2 Gy; range, 8.8-9.7 Gy) of the prescribed dose. The MOSFET readings and TPS doses in the body were similar (percentage difference range, -0.5% to 2.5%) and slightly higher in the shoulder and lung (percentage difference range, 4.0-5.5%). CONCLUSION: The FIF technique used for TBI provides homogenous dose distribution and is feasible, simple, and spares time compared with more-complex techniques. The TPS doses were similar to the midline doses obtained from MOSFET readings.

Dosimetric comparison of the field-in-field technique and tangential wedged beams for breast irradiation.

PURPOSE: To analyze tangential wedged beam and field-in-field (FIF) technique doses using dose-volume histograms and conformality indices for target volume and healthy tissues within the irradiated volume. MATERIALS AND METHODS: Thirty patients treated with breast-conserving surgery and postoperative whole breast radiotherapy were enrolled. Three plans were generated: a standard tangential plan with either one outer field wedge or bilateral wedges, and an FIF plan. Three indices were used: the dose homogeneity index (DHI), PTV dose improvement index (PDI(index)) and geometric conformity index (g). Also ipsilateral lung, heart and contralateral breast doses were compared for each plan. RESULTS: Dose homogeneity index was significantly lower for the FIF (0.117 ± 0.021) than for the single wedge (0.131 ± 0.025, p = 0.02) and double wedged plan (0.128 ± 0.025, p = 0.04), respectively. The g was significantly less in the FIF (0.70 ± 0.14) compared to the wedge plans (0.80 ± 0.17, p = 0.02 and 0.83 ± 0.16, p = 0.003). Contralateral breast doses were significantly lower in the FIF plan. The FIF plan significantly lowered MU compared to both the single wedge and bilateral wedge plans. CONCLUSION: The dose distribution within the target was more homogenous, and the doses for healthy tissue were less in the FIF plan compared to the tangential wedge plans.

Comparison of rectal volume definition techniques and their influence on rectal toxicity in patients with prostate cancer treated with 3D conformal radiotherapy: a dose-volume analysis.

BACKGROUND: To evaluate the impact of four different rectum contouring techniques and rectal toxicities in patients with treated with 3D conformal radiotherapy (3DCRT). METHODS: Clinical and dosimetric data were evaluated for 94 patients who received a total dose 3DCRT of 70 Gy, and rectal doses were compared in four different rectal contouring techniques: the prostate-containing CT sections (method 1); 1 cm above and below the planning target volume (PTV) (method 2); 110 mm starting from the anal verge (method 3); and from the anal verge to the sigmoid flexure (method 4). The percentage of rectal volume receiving RT doses (30-70 Gy) and minimum, mean rectal doses were assessed. RESULTS: Median age was 69 years. Percentage of rectal volume receiving high doses (>or= 70 Gy) were higher with the techniques that contoured smaller rectal volumes. In methods 2 and 3, the percentage of rectal volume receiving >or= 70 Gy was significantly higher in patients with than without rectal bleeding (method 2: 30.8% vs. 22.5%, respectively (p = 0.03); method 3: 26.9% vs. 18.1%, respectively (p = 0.006)). Mean rectal dose was significant predictor of rectal bleeding only in method 3 (48.8 Gy in patients with bleeding vs. 44.4 Gy in patients without bleeding; p = 0.02). CONCLUSION: Different techniques of rectal contouring significantly influence the calculation of radiation doses to the rectum and the prediction of rectal toxicity. Rectal volume receiving higher doses (>or= 70 Gy) and mean rectal doses may significantly predict rectal bleeding for techniques contouring larger rectal volumes, as was in method 3.