Comprehensive 3DCRT Hypofractionated Radiotherapy Schedule for Localized Prostate Adenocarcinoma in the Era of IMRT: Dosimetric and Endoscopic Analysis.

Background: Moderate hypofractionated radiotherapy (MHRT) has emerged as the preferred treatment modality for localized prostate cancer based on randomized controlled studies regarding efficacy and toxicity using contemporary radiotherapy techniques. In the setting of MHRT, available data on dosimetric parameters and late rectal toxicity are limited. Aim: To present the effects of MHRT on late rectal toxicity while conducting an extensive dosimetric analysis in conjunction with rectoscopy results. Methods: This is a prospective study including patients with intermediate-risk prostate adenocarcinoma. All patients were treated with MHRT 44 Gy in 16 fractions to the seminal vesicles and to the prostate, followed by a sequential boost to the prostate alone of 16.5 Gy in 6 fractions delivered with three-dimensional conformal radiation therapy (3DCRT). Acute and late toxicity were assessed. Endoscopy was performed at baseline, every 3 months post-therapy for the first year, and every 6 months for the year after. The Vienna Rectoscopy Score (VRS) was used to assess rectal mucosal injury related to radiotherapy. Dosimetric analysis for the rectum, rectal wall, and its subsegments (upper, mid, and low 1/3) was performed. Results: Between September 2015 and December 2019, 20 patients enrolled. Grade 1 late gastrointestinal toxicity occurred in 10% of the patients, whereas 5% had a grade ≥2. Twelve months post radiotherapy: 4 (20%) patients had VRS 1; 2 (10%) patients had VRS 2; 1(5%) patient had VRS 3. 24 months post radiotherapy, VRS 1 was observed in 4 patients (20%) and VRS 2 in 3 (15%) patients. The dosimetric analysis demonstrated noticeable variations between the rectum, rectal wall, and rectal wall subsegments. The dosimetric analysis of the rectum, rectal wall, and its mid and low segments with respect to rectoscopy findings showed that the higher dose endpoints V52.17Gy and V56.52Gy are associated with rectal mucosal injury. Conclusions: A thorough delineation of the rectal wall and its subsegments, together with the dosimetric analysis of these structures, may reduce late rectal toxicity. Dosimetric parameters such as V52.17Gy and V56.52Gy were identified to have a significant impact on rectal mucosal injury; additional dose endpoint validation and its relation to late GI toxicity is needed.

Dosimetric comparison and evaluation of two computational algorithms in VMAT treatment plans.

PURPOSE: This study aimed to assess the accuracy and dosimetric impact of the Acuros XB (AXB) algorithm compared to the Anisotropic Analytical Algorithm (AAA) in two situations. First, simple phantom geometries were set and analyzed; moreover, volumetric modulated arc therapy (VMAT) clinical plans for Head & Neck and lung cases were calculated and compared. METHODS: First, a phantom study was performed to compare the algorithms with radiochromic EBT3 film doses using one PMMA slab phantom and two others containing foam or air gap. Subsequently, a clinical study was conducted, including 20 Head & Neck and 15 lung cases irradiated with the VMAT technique. The treatment plans calculated by AXB and AAA were evaluated in terms of planning target volume (PTV) coverage (V95% ), dose received by relevant organs at risk (OARs), and the impact of using AXB with a grid size of 1 mm. Finally, patient-specific quality assurance (PSQA) was performed and compared for 17 treatment plans. RESULTS: Phantom dose calculations showed a better agreement of AXB with the film measurements. In the clinical study, AXB plans exhibited lower Conformity Index and PTV V95% , higher maximum PTV dose, and lower mean and minimum PTV doses for all anatomical sites. The most notable differences were detected in regions of intense heterogeneity. AXB predicted lower doses for the OARs, while the calculation time with a grid size of 1 mm was remarkably higher. Regarding PSQA, although AAA was found to exhibit slightly higher gamma passing rates, the difference did not affect the AXB treatment plan quality. CONCLUSIONS: AXB demonstrated higher accuracy than AAA in dose calculations of both phantom and clinical conditions, specifically in interface regions, making it suitable for sites with large heterogeneities. Hence, such dosimetric differences between the two algorithms should always be considered in clinical practice.

Implementation of TG-218 for patient-specific quality assurance tolerance and action limits determination: Gamma passing rate evaluation using 3DVH software.

PURPOSE: To determine the tolerance limit (TL) and action limit (AL) of gamma passing rates (%GP) for volumetric-modulated arc therapy (VMAT) patient-specific quality assurance (PSQA) according to the American Association of Physicists in Medicine (AAPM) Task Group (TG)-218 recommendations, and to comparatively evaluate the clinical relevance of 2D %GP and 3D %GP. METHODS: PSQA was performed for 100 head and neck (H&N) and 73 prostate cancer VMAT treatment plans. Measurements were acquired using a cylindrical water equivalent phantom, hollow in the center, allowing measurements with homogeneous or heterogeneous inserts. The LINAC-delivered dose distributions were compared to those calculated from the treatment planning system through the gamma index. TL and AL were determined through the computation of two-dimensional (2D) %GP using the recommended acceptance criteria. Dose-volume histograms were reconstructed from the measurements using a commercially available software to detect the dosimetric errors (%DE) between the compared dose distributions. Utilizing the estimated dose on the patient anatomy, structure-specific %GP (3D %GP) were calculated. The 3D %GP were compared to the 2D %GP ones based on their correlation with the %DE. Each metric's sensitivity was determined through receiver operator characteristic analysis. RESULTS: TL and AL were in concordance with the universal ones, regarding the prostate cancer cases, but were lower for the H&N cases. Evaluation of %DE did not deem the plans unacceptable. The 2D %GP and the 3D %GP did not differ significantly regarding their correlation with %DE. For prostate plans, %GP sensitivity was higher than for H&N cases. CONCLUSIONS: Determination of institutional-specific TL and AL allows the monitoring of the PSQA procedure, yet for plans close to the limits, clinically relevant metrics should be used before they are deemed unacceptable for the process to be of higher sensitivity and efficiency.

Low dose total skin electron beam therapy for the management of T cell cutaneous lymphomas.

Mycosis fungoides (MF) represent the most common type of primary cutaneous lymphomas. Total skin electron beam (TSEB) therapy to a total skin administered dose of 36 Gy represents a very effective treatment regimen and its role in the management of MF is well established. Unfortunately, the issue in MF is that despite the proved effectiveness of radiation therapy, disease regress, and the main goal of TSEB treatment seems to be the prolongation of the overall response duration time. Taking into consideration the high radio-sensitivity of the disease, lower radiation doses have been tested with acceptable and comparable results. We prospectively analyzed low dose TSEB in 14 patients treated at ATTIKON University Hospital from 2011 to 2017. After a median duration of follow up time of 39 months we found that low dose TSEB is an effective treatment option, since therapeutic results are more than acceptable, with minimal toxicity. The fact that it can be repeated safely in the natural course of a "regressive" disease makes it more attractive than the standard full dose scheme of 36 Gy.

Probing the Effects of Ionizing Radiation on Young's Modulus of Human Erythrocytes Cytoskeleton using Atomic Force Microscopy.

PURPOSE/AIM: In this work, we examined the possible effects of ionizing radiation (IR) on biomechanical properties of the membrane-cytoskeleton of human erythrocytes, after X-ray irradiation. MATERIALS AND METHODS: Whole human blood from three healthy middle-aged volunteers was drawn by venipuncture and stored in tubes containing anticoagulant. Six blood samples were collected for each volunteer. Five of them were irradiated in the range of 0.1 Gy-2.0 Gy doses and one was used as control. The morphology and the elastic modulus of the erythrocytes were examined using atomic force microscopy and just few drops of whole blood. RESULTS: No morphological changes appeared according to the shape and the morphology of the erythrocytes. The elastic modulus of the irradiated samples was reduced with the increase of radiation dose. The findings indicate that X-ray irradiation affects the biomechanical properties of erythrocyte cytoskeleton. The mean value of Young's modulus of all the irradiated blood samples was significant difference from the control at a level, P < 0.01. CONCLUSIONS: The elastic modulus of the erythrocytes could be an indicator of the adverse effect in the human blood generated by IR exposure through a radiotherapy treatment.

Clinical application of Total Skin Electron Beam (TSEB) therapy for the management of T cell cutaneous lymphomas. The evolving role of low dose (12 Gy) treatment schedule.

BACKGROUND & PURPOSE: Although rare, cutaneous lymphomas represent a separate entity in hematologic oncology. T cell origin lymphomas are most common, with Mycosis Fungoides (MF) accounting for about 50-70% of cases. Sezary Syndrome (SS), which represents the leukemic varian of MF, accounts for 3% of Cutaneous T Cell Lymphomas (CTCL). Total Skin Electron Beam Therapy (TSEB) is included at the mainstream of treatment choices for CTCL. The scope of this study is to evaluate the effectiveness and toxicity of two treatment schedules of TSEB. METHODS AND MATERIALS: We report our experience with TSEB in the management of MF and SS, as of 14 patients treated in our institution from 2011 to 2015. 8 patients received the 12 Gy (low dose) scheme while 6 patients were managed with 36 Gy (standard or full dose scheme) according to six dual field Stanford technique. The endpoints were overall response rate, duration of response and toxicity of treatment. RESULTS: After a median follow up of 2.5 years we noted excellent treatment outcome, with both schemes being well tolerated and resulting in comparable response rates. The overall response rate for both treatment regimens was over 87.5%. Treatment was well tolerated with mild toxicity. CONCLUSION: The role of TSEB in the management of MF and SS is well established. The low dose TSEB schedule of 12 Gy is an effective treatment option, since therapeutic results are more than acceptable, compliance is excellent and toxicity is minimal. Moreover, the evidence that it can be repeated safely makes it more attractive than the standard 36 Gy scheme, when a patient is referred to radiation treatment according to treatment guidelines.

Determination of beam profile characteristics in radiation therapy using different dosimetric set ups.

PURPOSE: The purpose of this study was to analyze and to compare results regarding the penumbra size, flatness and symmetry obtained using six different measuring systems. METHODS: Beam profile measurements were performed in standard water phantom set-up for two photon beams for various square field sizes and for five electron beams for several applicator sizes at several depths. Six measuring systems were used: three ionization chambers; a Semiflex (31002, PTW), a Markus (23343, PTW) and a Roos (34001, PTW); Two semiconductor detectors; a p-type diode (60008, PTW) and an e-type diode (60017, PTW) and a one dimensional Linear Array (LA48, PTW). RESULTS: Our results indicate that penumbra size determination is strongly dependent on the measuring system. For the photon measurements the diodes showed the narrowest penumbra followed by the LA48, while the largest penumbra was presented by the Semiflex. The unshielded diode overestimates the penumbra in large field sizes and big depths. The parallel plate ionization chambers overestimate the penumbra width of electron beam profiles. The LA48 presents the most symmetric beam profiles. CONCLUSIONS: Regarding penumbra size determination, the LA48 can be considered acceptable in terms of accuracy, and is the most time-effective system. It is also adequate for symmetry and flatness measurements. For greatest possible accuracy silicon diode is recommended. Parallel plate ionization chambers are not appropriate for penumbra measurements.

A five split-field three dimensional conformal technique versus an anterior-posterior on in postoperative radiotherapy for gastric carcinoma: a multicenter comparative study using quality of life measurements as well as clinical and dosimetric parameters.

PURPOSE: Several adjuvant approaches are regarded as available options in the management of localized, resectable gastric cancer .The objective of our study was to evaluate multiple field and anteroposterior conformal technique. METHODS: Ninety-seven patients received three dimensional conformal (3DCRT) postoperative adjuvant radiation therapy for gastric carcinoma. Thirty-five patients received anteroposterior (AP/PA) fields (Group B), while 62 patients were irradiated with multifield technique (Group A). Their ages ranged between 29-85 years. The objective of the study was to evaluate the quality of life (QoL) for all patients after the completion of radiotherapy using the QLQ-C30 of the EORTC questionnaire (European Organization for Research and Treatment of Cancer) and to investigate any measurable differences between those two radiation techniques according to QUANTEC criteria and the radiotoxicity. RESULTS: In terms of QUANTEC criteria, the multifield technique was superior concerning the left kidney (p=0.025), right kidney (p<0.001), spinal cord (p<0.001) and planning target volume (PTV) coverage (p<0.001). According to EORTC/ RTOG toxicity criteria, the rate of diarrhea was higher in AP/ PA technique (p=0.028). In terms of QLQ-C30, the multifield technique was superior concerning appetite loss (p=0.022), diarrhea (p=0.046) and global QoL (p<0.001). CONCLUSION: On the basis of QLQ-C30 questionnaire, EORTC/ RTOG toxicity and dosimetric parameters, the present report has shown that the three dimensional multifield conformal radiotherapy is superior compared to AP-PA techniques.

Toxicity and efficacy of a hypofractionated (3 weekly fractions of 850c Gy) irradiation schedule for stage IIIb / IV non-small cell lung cancer elderly patients with low performance status and unfit for chemotherapy.

PURPOSE: To evaluate in an observational way the clinical impact of a hypofractionated irradiation schedule in patients with unresectable non-small cell lung cancer (NSCLC). METHODS: Forty elderly patients (24 men/16 women) diagnosed with unresectable stage IIIb/IV NSCLC unfit for chemotherapy, were treated with once-a-week hypofractionation schedule. All patients had a poor performance status. A dose of 255 Gy in 3 weekly fractions was prescribed while a 3D conformal technique (3D-CRT) was used for irradiation. The primary study endpoints were to assess the therapeutic impact of this schedule in terms of relapse free survival (RFS), overall survival (OS) survival and palliation of symptoms. The secondary endpoints were the evaluation of acute toxicity of the lung, esophagus and the skin. The intended followup was 3 years. The median age was 73.5 years (range 71-85). RESULTS: The median RFS was 12 months, while the median OS was 17 months. Symptoms relief was up to 20% for cough, 52.5% for haemoptysis, 40% for thoracic pain and 17.5% for dyspnoea. Acute lung toxicity in terms of radiation pneumonitis was recorded as 6/40 (15%) grade 1, 26/40 (65%) grade 2 and 8/40 (25%) grade 3. Additionally, grade 1 and 2 acute esophageal toxicity was recorded in 10/40 (25%) and 30/40 (75%) patients, respectively. Acute skin toxicity with grade 2 erythema was recorded in only 2/40 (5%) patients while most patients developed grade 1 skin erythema. Grade 3 late lung toxicity was recorded in 10/40 (25%) patients. CONCLUSIONS: This study showed that the proposed scheme has a moderate radiation-induced lung toxicity rate and an acceptable therapeutic ratio. Taking into consideration its cost effectiveness, the proposed hypofractionated scheme is a good alternative to conventional fractionation.

The impact of dose matrix and voxel dimensions to dose calculation for stereotactic radiosurgery.

PURPOSE: The purpose of the present study was the optimization of dose calculation for intracranial stereotactic radiosurgery. METHODS: We evaluated the Singular Value Decomposition (SVD) analysis as a novel optimization technique. Our approach to dose distribution optimization was to recover estimates of minibeams weights from well-defined provisional dose matrices. The dose delivered by a set of minibeams is formulated as a matrix equation. We studied the influence of dose matrix and voxel dimensions on the conditioning of stereotactic radiotherapy inverse problem. Dose matrix dimensions varied from 16 to 96 mm3, while voxel dimension was kept constant at 2 mm3. In the assessment of voxel dimension, matrix dimension was kept constant at 80 mm3 while voxel dimensions varied from 1 to 8 mm3. The reconstruction of dose distributions was studied using a truncated SVD expansion in the calculation of approximation to the generalised matrix inverse. RESULTS: The conditioning was deteriorated by either the decreasing of dose matrix dimensions or by the increasing of voxel size. The condition number was equal to 89×103 and 7×103 for the 16 mm3 and 96 mm3 dose matrix dimensions, respectively. The condition number was equal to 9.9×103 and to 2.7×106 for 1 mm3 and 8 mm3 voxel size, respectively. The reconstruction of dose distributions revealed that an ill-conditioned problem yields poor quality reconstruction. CONCLUSION: We considered that a good compromise between quality of dose distribution, time calculation and hard disk memory would be the use of a 64 mm3 matrix dimension with a 2 mm3 voxel size.

Review of the three-field techniques in breast cancer radiotherapy.

Breast cancer is often treated with radiotherapy (RT), with two opposing tangential fields. When indicated, supraclavicular lymph nodes have to be irradiated, and a third anterior field is applied. The junction region has the potential to be over or underdosed. To overcome this problem, many techniques have been proposed. A literature review of 3 Dimensional Conformal RT (3D CRT) and older 3-field techniques was carried out. Intensity Modulated RT (IMRT) techniques are also briefly discussed. Techniques are categorized, few characteristic examples are presented and a comparison is attempted. Three-field techniques can be divided in monoisocentric and two-isocentric. Two-isocentric techniques can be further divided in full field and half field techniques. Monoisocentric techniques show certain great advantages over two-isocentric techniques. However, they are not always applicable and they require extra caution as they are characterized by high dose gradient in the junction region. IMRT has been proved to give better dosimetric results. Three-field matching is a complicated procedure, with potential of over or undredosage in the junction region. Many techniques have been proposed, each with advantages and disadvantages. Among them, monoisocentric techniques, when carefully applied, are the ideal choice, provided IMRT facility is not available. Otherwise, a two-isocentric half beam technique is recommended.

A Retrospective Analysis of Toxicity and Efficacy for 2 Hypofractionated Irradiation Schedules Versus a Conventional One for Post-Mastectomy Adjuvant Radiotherapy in Breast Cancer.

INTRODUCTION: The aim of this analysis was a retrospective evaluation of the efficacy and toxicity of 2 hypofractionated irradiation schedules compared to conventional therapy in post-mastectomy patients. METHODS: 3 irradiation schedules were analyzed: 48.30 Gy in 21 fractions (group A, n = 60), 42.56 Gy in 16 fractions (group B, n = 27) and 50 Gy in 25 fractions (group C, n = 30) of the front chest wall. All groups were also treated with a supraclavicular field, with 39.10 Gy in 17 fractions (group A), 37.24 Gy in 14 fractions (group B) or 45 Gy in 25 fractions (group C). RESULTS: No local recurrences were noted in any group during 36 months of follow-up. Acute skin toxicity presented in all groups, with 58.3%, 70.4% and 60% of grade I; 35%, 25.9% and 40% of grade II; 6.7%, 3.7% and 0% of grade III being seen in groups A, B and C, respectively. Late skin toxicity was noted only as grade I in 16.7%, 25.9% and 26.7% of groups A, B and C, respectively. No significant difference was noted among all groups for either acute or late skin toxicity, or for radio-pneumonitis (chi2 test, p > 0.05). CONCLUSION: All schedules were equally effective with equivalent toxicity. A prospective randomized study is needed to confirm our results.

Transformation of physical DVHs to radiobiologically equivalent ones in hypofractionated radiotherapy analyzing dosimetric and clinical parameters: a practical approach for routine clinical practice in radiation oncology.

PURPOSE: The purpose of this study was to transform DVHs from physical to radiobiological ones as well as to evaluate their reliability by correlations of dosimetric and clinical parameters for 50 patients with prostate cancer and 50 patients with breast cancer, who were submitted to Hypofractionated Radiotherapy. METHODS AND MATERIALS: To achieve this transformation, we used both the linear-quadratic model (LQ model) and the Niemierko model. The outcome of radiobiological DVHs was correlated with acute toxicity score according to EORTC/RTOG criteria. RESULTS: Concerning the prostate radiotherapy, there was a significant correlation between RTOG acute rectal toxicity and D50 (P < 0.001) and V60 (P = 0.001) dosimetric parameters, calculated for α/ß = 10 Gy. Moreover, concerning the breast radiotherapy there was a significant correlation between RTOG skin toxicity and V(≥60) dosimetric parameter, calculated for both α/ß = 2.3 Gy (P < 0.001) and α/ß = 10 Gy (P < 0.001). The new tool seems reliable and user-friendly. CONCLUSIONS: Our proposed model seems user-friendly. Its reliability in terms of agreement with the presented acute radiation induced toxicity was satisfactory. However, more patients are needed to extract safe conclusions.

Measurement of systolic and diastolic arterial wall shear stress in the ascending aorta.

PURPOSE: Wall shear stress (WSS) appears to contribute significantly in the initiation and progression of atherosclerotic disease. The purpose of this work is to present in vivo systolic and diastolic WSS calculations in the human ascending aorta by the application of three straightforward methodologies based on Poiseuille's theory of flow. MATERIALS AND METHODS: Blood flow measurements were performed retrospectively in the ascending aorta of 20 non-atherosclerotic patients using phase-contrast MRI. WSS calculations were performed assuming Poiseuille's theory of flow based on average flow volume, average flow velocity and maximum flow velocity. Systolic and diastolic WSS values were calculated and compared with the calculated maximum and minimum values of WSS throughout the cardiac cycle. RESULTS: Systolic WSS values calculated by average flow volume, average flow velocity and maximum flow velocity were similar (0.4+/-0.2N/m(2), 0.4+/-0.3N/m(2)and 0.4+/-0.2N/m(2), respectively). Diastolic WSS values calculated by maximum flow velocity were significantly higher (11.6+/-7.0x10(-2)N/m(2)) compared to values calculated by average flow volume (0.3+/-0.9x10(-2)N/m(2)) and average flow velocity (0.3+/-1.0x10(-2)N/m(2)). Comparison of systolic and diastolic WSS values with maximum and minimum WSS values showed that time instances of maximum and minimum blood flow velocities do not coincide with time instances of maximum and minimum blood flow volume. CONCLUSION: In vivo calculation of WSS in the ascending aorta is feasible by phase-contrast MRI flow measurements and straightforward methodologies based on Poiseuille's theory of flow. However, measurements based on maximum flow velocity show larger deviations compared to measurements based on mean flow volume or mean flow velocity.