Patient-specific quality assurance for intracranial cases in robotic radiosurgery system.

PURPOSE: The purpose of this study was to perform pretreatment patient-specific quality assurance (QA) for intracranial irradiation using CyberKnife with an ion chamber. METHODS: Twenty-five intracranial plans created using the ray-tracing algorithm were used for this study. Computed tomography (CT) images of the water-equivalent RW3 slab phantom with PinPoint ionization chamber were acquired with 1-mm slice thickness and transferred to the MultiPlan treatment planning system (TPS). Four gold fiducial markers embedded into two different plates were used to tracking during the irradiation. Intracranial plans were transferred to CT images of the RW3 phantom. The isodose curves and sensitive volume of ion chamber were overlapped. Point dose measurements were performed three times and the mean point doses were calculated for each plan. The mean doses measured by the PinPoint ion chamber were compared with those of the calculated by MultiPlan TPS in the sensitive volume of PinPoint. RESULTS: The mean percentage difference (MPD) in point dose measurements was -2.44±1.97 for 25 plans. The maximum and minimum percentage differences between the measured and calculated absolute point doses were -7.14 and 0.23, respectively. The MPD was -1.70±1.90 for 12 plans using a fixed collimator and -3.11±1.86 for 13 plans using an IRIS cone. CONCLUSIONS: Point dose measurement is a reliable and functional method for pre-treatment patient-specific QA in intracranial CyberKnife plans. Point dose verification should be performed to correct any possible errors prior to patient treatment. It is recommended for use in patient-specific QA process in the CyberKnife plans.

A dosimetric comparison for SBRT plans of localized prostate cancer between Cyberknife and Varian Truebeam STX device.

As the Stereotactic Body Radiotherapy (SBRT) approach began to increase in treating patients with localized prostate cancer, it became necessary to investigate which methods used in practice were better. The aim of this study is to perform a dosimetric comparison of the advantages and disadvantages of SBRT treatments for localized prostate cancer delivered by CyberKnife (CK) and Varian Truebeam STX (FF and FFF). Seventeen intermediate and high-risk patients with localized prostate cancer were included in the study. SBRT plans for the CK system and Varian Truebeam STX systems with and without Flattening Filters (Tru-FF and Tru-FFF) were prepared for each patient. Plans prepared for each patient were planned at a fraction dose of 6.7 Gy at 6 MV energy and a target dose of 33.5 Gy in 5 fractions. For all plans, cumulative dose-volume histograms (DVHs) were generated for target volumes and organs at risk (OAR). The maximum doses of PTV (41 Gy) in CK plans are higher than the maximum doses (35 Gy) in VMAT plans prepared with Tru-FF or Tru-FFF beams. The mean dose of the rectal wall (10.06 ± 2.40Gy for CK) is still relatively low compared to other plans (13.46 ± 2.16 Gy for Tru-FF and 13.61 ± 2.32 Gy for Tru-FFF). The bladder wall (14 Gy for CK, 26 Gy for Tru-FF and Tru-FFF) and femoral head (6.8 Gy for CK, 9 Gy for Tru-FF and 9.4 Gy Tru-FFF) doses were also lower for CK plans. The CK plans provide better tumour control due to low doses in critical organs and high target doses than the Tru-FF or Tru-FFF plans. It was observed that CK and VMAT plans for SBRT with 6 MV photon beams provided acceptable results in term of treatment planning criteria such as Conformity Index and Homogeneity Index. It is recommended to use a target tracking system to provide an accurate and reliable SBRT treatment with VMAT and CK techniques.

Promising Outcomes in Acromegaly Patients Receiving CyberKnife Stereotactic Hypofractionated Radiotherapy.

BACKGROUND: The primary treatment for patients with acromegaly has traditionally been transsphenoidal surgery, with decreasing reliance on radiotherapy (RT) due to advancements in pharmacotherapy (PT). Despite these advancements, a substantial portion of patients still face persistent acromegaly, necessitating novel treatment approaches. This study investigates the role of CyberKnife Stereotactic Hypofractionated Radiotherapy (CK-HFRT) in persistent acromegaly. OBJECTIVE: The primary objective was to assess the impact of CK-HFRT on endocrine remission (ER) rates while maintaining acceptable toxicity levels. METHODS: The study retrospectively analyzed 31 consecutive patients with acromegaly who received CK-HFRT following multiple unsuccessful surgeries and prolonged PT without ER. Various CK-HFRT dose fractionation regimes were administered, and dose volume histograms were evaluated. Tumor control, cured disease (CD), endocrine remission (ER) rates, and overall survival were estimated at a median follow-up of 62 months. Acute and late toxicity, including pituitary insufficiency and radiation-induced optic neuropathy (RION), were also assessed. RESULTS: At 62 months of follow-up, the study group demonstrated excellent tumor control with 100% nonprogressive adenomas. Endocrine remission was achieved in 86.7% of patients, with a 22.4% CD rate at five years. Pituitary insufficiency occurred in 32.3% of patients, and no cases of RION were reported. The study observed three deaths related to cardiovascular diseases, all in patients receiving PT. Overall survival at five years was 79.2%. CONCLUSION: CyberKnife stereotactic hypofractionated radiotherapy, as an adjunct to PT, provides a viable treatment option for patients with persistent acromegaly following unsuccessful surgeries. The therapy results in substantial ER rates and tumor control while minimizing the risk of permanent radiation-induced optic neuropathy. However, the decision to administer CK-HFRT should be individualized, considering the patient's overall condition and treatment history.

Investigation of approaches for internal target volume definition using 4-dimensional computed tomography in stereotactic body radiotherapy of lung cancer.

The present study was undertaken to investigate the suitability of alternative internal target volume (ITV) delineation strategies based on maximum intensity projection (MIP), average intensity projection (AIP), 2 extreme phases and 4 phases images relative to the ITV10phase in stereotactic body radiation therapy (SBRT) for lung cancer. The 4-dimensional computed tomography (4DCT) data of 15 lung cancer patients treated with SBRT in our clinic were used. Five different ITVs were generated as follows: merging GTVs from 10 phases (ITV10Phase); merging GTVs from 2 extreme phases (0%, 50%) (ITV2Phase); merging GTVs from 4 phases (0%, 20%, 50%, and 70%) (ITV4Phase); delineating GTV on MIP (ITVMIP), and delineating GTV on AIP (ITVAIP). PTV10Phase, PTV2Phase, PTV4Phase, PTVMIP, and PTVAIP were generated by adding a 5-mm margin around the related ITV. Volumetric analyses were performed for 4 ITVs and PTVs relative to ITV10phase and PTV10phase. SBRT plans made for all PTVs were evaluated for dosimetric effect of alternative ITV delineation strategies. The mean percentage overlap volume (POV) for PTV2phase, PTV4phase, PTVMIP, and PTVAIP relative to PTV10phase were 84.2 ± 5.4%, 92.0 ± 2.9%, 82.2 ± 5.7%, and 73.8 ± 9.3%, for lower-lobe tumors, respectively. The mean POV for PTV2phase, PTV4phase, PTVMIP, and PTVAIP relative to PTV10phase were 93.2 ± 2.5%, 95.9 ± 1.0%, 87.5 ± 6.7%, and 83.3 ± 6.8% for upper-lobe, respectively. For lower-lobe tumors the mean differences in V20 and MLD for plans based on PTV2phase and PTV4phase were <0.5% and <10 cGy, compared with a plan based on PTV10phase. The use of PTV based on 4 respiratory phases and a 5-mm margin is a safe approach to reduce the workload of target delineation for tumors located in both lower and upper lobes.

Surface dose measurements with GafChromic EBT film for 6 and 18MV photon beams.

The aim of this study was to determine the surface doses using GafChromic EBT films and compare them with plane-parallel ionization chamber measurements for 6 and 18 MV high energy photon beams. The measurements were made in a water equivalent solid phantom in the build-up region of the 6 and 18MV photon beams at 100 cm SSD for various field sizes. Markus type plane-parallel ion chamber with fixed-separation between collecting electrodes was used to measure the percent depth doses. GafChromic EBT film measurements were performed both on the phantom surface and maximum dose depth at the same geometry with ion chamber measurements. The surface doses found using GafChromic EBT film were 15%, 20%, 29%and 39%+/-2% (1SD) for 6 MV photons, 6%, 11%, 23% and 32%+/-2% (1SD) for 18 MV photons at 5, 10, 20 and 30 cm(2) field sizes, respectively. GafChromic EBT film provides precise measurements for surface dose in the high energy photons. Agreement between film and plane-parallel chamber measurements was found to be within +/-3% for 18 MV photon beams. There was 5% overestimate on the surface doses when compared with the plane-parallel chamber measurements for all field sizes in the 6 MV photon beams.

A column generation heuristic for VMAT planning with adaptive CVaR constraints.

In this study we develop an efficient computational procedure that generates medically acceptable treatment plans for volumetric modulated arc therapy with constant gantry speed. Our proposed method is a column generation heuristic based on a mixed integer linear programming model, where the objective function contains minimization of total monitor unit of the treatment plan and dose-volume requirements are included as conditional value-at-risk constraints. Our heuristic generates a full treatment arc for the restricted master problem and calibrates the right hand side parameters of the conditional value-at-risk constraints in the first phase. In the second phase, this initial solution is improved by performing column generation. This is a fully automated procedure and produces treatment plans in a single call without any human intervention. We evaluate its performance on real prostate cancer data by comparing the quality of the generated plans with those obtained by a widely used commercial treatment planning system. Our analysis shows that the results are promising, and the generated plans satisfy the prescription restrictions and require [Formula: see text] fewer monitor units on average compared to the ones obtained using Eclipse.

Toxic-dose warfarin-induced apoptosis and its enhancement by gamma ionizing radiation in leukemia K562 and HL-60 cells is not mediated by induction of oxidative stress.

The purpose of this study was to test the hypothesis that warfarin may enhance free radical production and oxidative damage on cancer cells. We examined the possible concentration-dependent effect of warfarin on cytotoxicity with respect to oxidative stress on leukemia cell lines (K562 and HL-60) and normal human peripheral blood mononuclear cells (PBMC). Gamma radiation was used as a positive control agent for oxidative stress. At all concentrations of warfarin (5-200 muM), 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol)- and bis-N-methylacridinium nitrate (lucigenin)-amplified chemiluminescence responses and lipid peroxidation and protein oxidation were stable after 72 h incubation at 37 degrees C. However, The 2',7'-dichlorofluorescein diacetate (DCFH-DA) oxidation was increased when cells were incubated with high concentrations (50-200 muM) of warfarin. In these concentration ranges, warfarin reduced cell growth in a dose-dependent manner, producing apoptosis. Our results also revealed that at concentrations above 5 muM, warfarin had a potentiating effect on radiation-mediated growth inhibition and apoptosis. Furthermore, marked effects were observed on leukemic cells compared with PBMC. We report here that the increase of DCFH oxidation might be due to the increase in the release of cytochrome C caused by warfarin, as cytosolic cytochrome C content was significantly elevated in the warfarin-treated cells compared with control cells, and because cotreatment with antioxidants N- acetylcysteine or 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron) was unable to prevent cytochrome C release and DCFH oxidation induced by the drug. Taken together, these results suggest that high warfarin concentrations may be toxic to leukemic cells in vitro through apoptosis, although at the pharmacological concentrations (<50 muM), warfarin has no prooxidant or cytotoxic effect on PBMC, K562, and HL-60 cells. In addition, when the treatment of leukemic cells with warfarin at concentrations above 5 muM is combined with radiation, we observed an increase in radiation-induced cytotoxicity. The mechanism by which warfarin potentiates this cytotoxicity is unclear, but it may not be directly due to toxic damage induced by warfarin-generated free radicals.

Conventionally Fractionationed Volumetric Arc Therapy versus Hypofractionated Stereotactic Body Radiotherapy: Quality of Life, Side Effects, and Prostate-Specific Antigen Kinetics in Localized Prostate Cancer.

OBJECTIVES: To compare conventionally fractionationed volumetric arc therapy (VMAT) and hypofractionated stereotactic body radiotherapy (SBRT) modalities in terms of prostate-specific antigen (PSA) kinetics, toxicity, and quality of life (QOL) in patients with localized prostate cancer. METHODS: Patients received radical radiotherapy as either 33.5 Gy/5 fr for SBRT or 75.6 Gy/35 fr for VMAT. International Prostate Symptom Score (IPSS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (QLQ-PR25) forms were used to assess QOL. RESULTS: Of the 48 patients (28 in SBRT and 20 in VMAT) included in the study, 40 (20 in SBRT and 20 in VMAT) were evaluated for QOL status. PSA control rate was 100% and PSA nadir value was 0.5 ng/dl in both arms during the median follow-up period of 23 months. The magnitude of PSA bounce was higher in the SBRT arm than in the VMAT arm (P = 0.01). The PSA decline rate in the VMAT arm was higher than in the SBRT arm (P = 0.028). Three (10.7%) patients treated with SBRT who had a history of transurethral resection of the prostate (TURP) experienced grade 3 urinary toxicity. No significant difference was observed concerning sexual activity and sexual functioning scores, whereas scores at 10.5 and 13.5 months were decreased in both arms. The SBRT and VMAT arms had similar urinary incontinence, bowel symptoms, and IPSS obstruction scores. The magnitude of increase in IPSS scores at treatment completion was higher in the VMAT arm than in the SBRT arm (P = 0.046). The decrease in hormonal symptom scores at 4.5, 10.5, and 13.5 months was higher in the VMAT arm than in the SBRT arm (P = 0.007, 0.027, and 0.021, respectively). CONCLUSIONS: Both treatment modalities had similar effectiveness and provided acceptable outcomes in terms of toxicity and QOL. Grade 3 urinary toxicities might be eliminated with careful patient selection for SBRT.

A comparison of TPS and different measurement techniques in small-field electron beams.

In recent years, small-field electron beams have been used for the treatment of superficial lesions, which requires small circular fields. However, when using very small electron fields, some significant dosimetric problems may occur. In this study, dose distributions and outputs of circular fields with dimensions of 5cm and smaller, for nominal energies of 6, 9, and 15MeV from the Siemens ONCOR Linac, were measured and compared with data from a treatment planning system using the pencil-beam algorithm in electron beam calculations. All dose distribution measurements were performed using the Gafchromic EBT film; these measurements were compared with data that were obtained from the Computerized Medical Systems (CMS) XiO treatment planning system (TPS), using the gamma-index method in the PTW VeriSoft software program. Output measurements were performed using the Gafchromic EBT film, an Advanced Markus ion chamber, and thermoluminescent dosimetry (TLD). Although the pencil-beam algorithm is used to model electron beams in many clinics, there is no substantial amount of detailed information in the literature about its use. As the field size decreased, the point of maximum dose moved closer to the surface. Output factors were consistent; differences from the values obtained from the TPS were, at maximum, 42% for 6 and 15MeV and 32% for 9MeV. When the dose distributions from the TPS were compared with the measurements from the Gafchromic EBT films, it was observed that the results were consistent for 2-cm diameter and larger fields, but the outputs for fields of 1-cm diameter and smaller were not consistent. In CMS XiO TPS, calculated using the pencil-beam algorithm, the dose distributions of electron treatment fields that were created with circular cutout of a 1-cm diameter were not appropriate for patient treatment and the pencil-beam algorithm is not convenient for monitor unit (MU) calculations in electron dosimetry.

Differential expression of long non-coding RNAs during genotoxic stress-induced apoptosis in HeLa and MCF-7 cells.

Long non-coding RNAs (lncRNAs) are emerging as new players in cancer as they are implicated in diverse biological processes and aberrantly expressed in a variety of human cancers. No data are available on their function under genotoxic stress-induced apoptosis. In this work, we assessed the behavior of some candidate lncRNAs (HOTAIR, MALAT1, TUG1, lincRNA-p21, GAS5, MEG3, PANDA, UCA1, ANRIL, and CCND1) during DNA damage-induced cell death in HeLa and caspase-3-deficient MCF-7 cells using bleomycin (BLM) and γ-radiation to induce DNA damage. Cells were incubated in the presence of BLM for 24 h or irradiated. Apoptosis was analyzed by measurement of oligonucleosomal fragmentation of nuclear DNA. Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. The decline in the expression of HOTAIR (approx. twofold, p < 0.01) and MALAT1 (approx 1.6-fold, p < 0.01) was clearly evident in BLM-treated HeLa and MCF cells (only HOTAIR, fivefold, p < 0.01). For lincRNA-p21, ncRNA-CCND1, and MEG3, a similar up-regulation pattern was obvious in both cell lines where the increase was generally more pronounced in BLM-treated cells. Interestingly, the induction of ANRIL and GAS5 was mainly restricted to irradiated cells. In conclusion, our findings reveal a differential regulation of individual lncRNAs during genotoxic stress-induced apoptosis.

Surface dose and build-up region measurements with wedge filters for 6 and 18 MV photon beams.

PURPOSE: High-energy photons are most commonly used in radiotherapy to treat cancer. Wedge filters are required to obtain homogeneous dose distribution in the patient. Different wedge filter types create different surface doses. In this study, the effect of the virtual and physical wedge filters on the surface and build-up region doses was examined for 6- and 18-MV high-energy photon beams. MATERIALS AND METHODS: The measurements were made in a water equivalent phantom in the build-up region at a 100-cm source-to-surface distance for various field sizes using virtual and physical wedge filters having different angles. A parallel-plate ion chamber was used to measure the percent depth doses. RESULTS: The percentage dose at the surface increased as the field size increased for open, virtual, and physical wedged beams. For open, physical, and virtual wedged beams, the surface doses were found to be 15.4%, 9.9%, and 15.9% with 6-MV photons and 10.6%, 8.8%, 11.9% with 18-MV photons, respectively, at 10 x 10 cm(2) field size. CONCLUSION: Build-up doses of virtual wedged beams were similar to those of open beams. Surface and buildup doses of physical wedged beams were lower than those of open and virtual wedged beams.

The effect of oblique electron beams to the surface dose under the bolus.

The aim of this study is to determine the effect of bolus to the surface dose in oblique electron incidences. Irradiations with 4.5, 6, 7.5, 9, and 12-MeV electron beams were made for the incidence angles of 0 degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees, 75 degrees and using 3 different bolus setups: (1) unbolused (no bolus), (2) 5-mm bolus, and (3) 10-mm bolus. A set of EBT gafchromic film pieces placed on the phantom surface was irradiated with a 400-cGy dose at D(max) for each setup. Whereas surface dose increased with increasing incidence degrees in the absence of a bolus, it was seen that there was a large surface dose decreasing in the presence of a bolus with increasing incidence angles. For 60 degrees incidence angle, the relative surface doses with unbolused setup were: 88.10%, 90.06%, 89.35%, 90.25%, and 97.10%; with 5-mm bolus: 66.45%, 81.20%, 99.78%, 124.43%, and 116.07%; and with 10-mm bolus: 22.65%, 45.20%, 55.20%, 65.82%, and 90.27% for 4.5, 6, 7.5, 9, and 12 MeV, respectively. The use of bolus in the treatment of highly oblique surfaces with low-energy electron beams significantly decreases the surface dose.