Derivation of equations to define inflection point and its analysis in flattening filter free photon beams based on the principle of polynomial function

Purpose: The objective of this work is to (1) present a mechanism for calculating inflection points on profiles at various depths and field sizes, and (2) study the doses at the inflection points for various field sizes at depth of maximum dose (Dmax) for flattening filter free (FFF) photon beam profiles. Methods: Graphical representation was done on percentage of dose versus inflection points. Also, using the polynomial function, the author formulated equations for calculating spot-on inflection point on the profiles for both the 6MV and 10 MV energies for different field sizes at various depths. Results: In a 10 MV FFF radiation beam, the dose at inflection point of the profile decreases as the field size increases. However, in 6MV FFF radiation beam, the dose at the inflection point initially increases with an increase in the field size up to 10 ×10 cm2 and decreases after 10 ×10 cm2. The polynomial function was fitted for both the 6 MV and 10 MV FFF beams for all field sizes and depths. Conclusion: Polynomial function is one of the easiest ways of identifying the inflection point in FFF beam for various field sizes and depths. Graphical representation of dose versus inflection point for both FFF energies was derived

Intensity modulated radiotherapy versus volumetric modulated arc therapy in breast cancer: A comparative dosimetric analysis

Purpose: Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) has the capacity to optimize the dose distribution. We analyzed the dosimetric differences of plans in treatment planning system (TPS) between VMAT and IMRT in treating breast cancer. Methods: Fourteen patients were simulated, planned, and treated with VMAT using single, double or partial arcs. IMRT treatments were generated using 4 to 5 tangential IMRT fields for the same patients. All treatment plans were planned for 50 Gy in 25 fractions. The VMAT and IMRT plans were compared using the planning target volume (PTV) dose and doses to the other organs at risk (OARs). Results: For the PTV, comparable minimum, mean, maximum, median, and modal dose as well equivalent sphere diameter of the structure (Equis) were observed between VMAT and IMRT plans and found that these values were significantly equal in both techniques. The right lung mean and modal doses were considerably higher in VMAT plans while maximum value was considerably lower when compared with IMRT plans. The left lung mean and modal doses were higher with VMAT while maximum doses were higher in IMRT plans. The mean dose to the heart and maximum dose to the spinal cord was lower with IMRT. The mean dose to the body was higher in VMAT plans while the maximum dose was higher in IMRT plans. Conclusion: Four field tangential IMRT delivered comparable PTV dose with generally less dose to normal tissues in our breast cancer treatment study. The IMRT plans typically had more favourable dose characteristics to the lung, heart, and spinal cord and body dose when compared with VMAT. The only minor advantage of VMAT for breast cases was slightly better PTV coverage

Histone deacetylase inhibitors synergize with sildenafil to suppress purine metabolism and proliferation in pulmonary hypertension

RATIONALE: Sildenafil, a well-known vasodilator known to interfere with purinergic signaling through effects on cGMP, is a mainstay in the treatment of pulmonary hypertension (PH). However, little is known regarding its effects on the metabolic reprogramming of vascular cells, which is a hallmark of PH. Purine metabolism, especially intracellular de novo purine biosynthesis is essential for vascular cell proliferation. Since adventitial fibroblasts are critical contributors to proliferative vascular remodeling in PH, in this study we aimed to investigate if sildenafil, beyond its well-known vasodilator role in smooth muscle cells, impacts intracellular purine metabolism and proliferation of fibroblasts derived from human PH patients. METHODS: Integrated omics approaches (plasma and cell metabolomics) and pharmacological inhibitor approaches were employed in plasma samples and cultured pulmonary artery fibroblasts from PH patients. MEASUREMENTS AND MAIN RESULTS: Plasma metabolome analysis of 27 PH patients before and after treatment with sildenafil, demonstrated a partial, but specific effect of sildenafil on purine metabolites, especially adenosine, adenine, and xanthine. However, circulating markers of cell stress, including lactate, succinate, and hypoxanthine were only decreased in a small subset of sildenafil-treated patients. To better understand potential effects of sildenafil on pathological changes in purine metabolism (especially purine synthesis) in PH, we performed studies on pulmonary fibroblasts from PAH patients (PH-Fibs) and corresponding controls (CO-Fibs), since these cells have previously been shown to demonstrate stable and marked PH associated phenotypic and metabolic changes. We found that PH-Fibs exhibited significantly increased purine synthesis. Treatment of PH-Fibs with sildenafil was insufficient to normalize cellular metabolic phenotype and only modestly attenuated the proliferation. However, we observed that treatments which have been shown to normalize glycolysis and mitochondrial abnormalities including a PKM2 activator (TEPP-46), and the histone deacetylase inhibitors (HDACi), SAHA and Apicidin, had significant inhibitory effects on purine synthesis. Importantly, combined treatment with HDACi and sildenafil exhibited synergistic inhibitory effects on proliferation and metabolic reprogramming in PH-Fibs. CONCLUSIONS: While sildenafil alone partially rescues metabolic alterations associated with PH, treatment with HDACi, in combination with sildenafil, represent a promising and potentially more effective strategy for targeting vasoconstriction, metabolic derangement and pathological vascular remodeling in PH

Advantage of using deep inspiration breath hold with active breathing control and image-guided radiation therapy for patients treated with lung cancers

Purpose: The aim of this study was to evaluate the irradiated volume and doses to the target, heart, left lung, right lung and spinal cord, the number of segments and treatment time by using moderated deep inspiration breath hold (mDIBH) with active breathing control (ABC) and image-guided radiotherapy (IGRT) for patients treated with lung cancers.Methods: The suitability of this technique for lung patient treated with ABC was investigated and the solutions to achieve better treatments were discussed. Eleven lung cancer patients (3 left-sided and 8 right sided lesions) with stages I-III underwent standard free breath (FB) and ABC computed tomography (CT) scans in the treatment supine position. This can be achieved by applying respiratory manoeuvres, such as mDIBH, during which the threshold volume utilized is defined as 75-80% of the maximum aspiratory capacity. Five to seven, 6-MV photon beams with optimized gantry angles were designed according to the tumor location to conform to the PTV while sparing as much heart, spinal cord, and contra lateral lung as possible. For eleven patients, treatment planning using mDIBH CT data with intensity modulated radiation therapy (IMRT) was then reoptimized on the free breathing data set for comparison. The studied parameters of the plans for each patient were evaluated based on the average of the minimum, mean, and maximum difference in dose, the range of difference, and the p-value using two-tailed paired t test assuming equal variance.Results: The average volume of the planning target volume (PTV) in 11 patients increased to 1.32% in ABC compared to FB. The average volume of heart in 11 patients decreased to 2.9% in ABC compared to free breathing IMRT. In the case of lungs, the volume increased to 27.5% and 25.85% for left and right lungs, respectively. The range of mean difference in dose to the PTV in 11 patients was -54 cGy to 230 cGy with ABC technique when compared with free breathing. The range of mean dose difference of heart in 11 patients observed were -88 cGy to 66 cGy (p < 0.0410) between ABC and FB. The range of maximum dose difference to the spinal cord in 11 patients were -1592 cGy to 190 cGy (p < 0.041) with ABC technique when compared with FB IMRT. Monitor units (MUs) were -22.9% less in ABC compared to FB. Segments were more in ABC compared to FB for about 16.39% on an average. The average of minimum, mean and maximum difference in dose to the right lung and left lung were less in ABC compared with FB.Conclusion: In most of the cases, IGRT with ABC significantly reduces the mean dose to heart, right lung, left lung, and spinal cord compared with FB. Discrepancy observed in few cases made the statistical data inconsistent. Depending on anatomy and arbitrary phase of the breathing cycle, the results may vary and for better outcome of the results optimum treatment procedures need to follow.

Commissioning and quality assurances of the Intrabeam Intra-Operative radiotherapy unit

Purpose: The authors report comprehensive commissioning and quality assurance (QA) procedures for Intrabeam, Intra-Operative radiotherapy (IORT) unit. The Intrabeam system miniature X-ray source is a 50 kV and 40 µA unit. Methods: The authors’ tests include measurements of output, beam deflection, isotropy, kVp and mAs measurements, quality index, isodose, reproducibility, linearity, depth dose verification, and 3D dose distribution. IC ionization chamber and the UNIDOSE dosimeter were used for the output commissioning. Probe adjuster/ionization chamber holder (PAICH) was used to check the mechanical straightness of the probe. For radiation tests, NACP parallel plate chamber, Standard Imaging electrometer, 30 × 30 × 30 cm3 IAEA water phantom, solid water slabs, EDR-2 Films with RIT software, and ionization based survey meters were used. Unfors Xi platinum edition kVp meter was used to measure the kVp and mAs. Results: In mechanical QA test, X-Beam position (-0.09 mm), Y-Beam position (0.01 mm), and radial position (0.11 mm) errors were within the tolerance level. Isotropy test with PDA, survey meter, ion chamber, and film measurements also produced results within the specifications. Output measurements with PAICH and external chamber measurements were matched. Beam quality, linearity, and reproducibility values were ascertained at 50KV and 40 µA and found to be within limits. Isodose, 3D dose distribution, transverse, and horizontal profiles showed the good isotropy of the source. Conclusion: The authors’ methodology provides comprehensive commissioning and calibration procedures for the Intrabeam system

Radiotherapy for large cutaneous angiosarcoma of face with RapidArc (VMAT)

Angiosarcoma is a rare malignancy of vascular origin. It can affect any part of the body, head and neck region being probably the most common site of diagnosis. We present here a case of Angiosarcoma of face in a 67-year-old elderly gentleman who was treated with RapidArc – volumetric modulated arc therapy (VMAT) for recurrence after surgery, radiotherapy and chemotherapy. As an alternative to Electron Beam Therapy, RapidArc with skin bolus can be considered for large complex shaped targets with irregular surface and tissue inhomogeneity. RapidArc plan can achieve adequate target coverage with acceptable dose homogeneity and conformity

Study of inter-fraction movements of tongue during radiation therapy in cases of tongue malignancy using volumetric cone beam computed tomography (CBCT) imaging

Purpose: Tongue is a mobile organ in head and neck region predisposing it for geographic miss during the course of fractionated radiotherapy for tongue malignancy. This study analyses movement of tongue during the course of radiotherapy using volumetric KV-cone beam computed tomography (KV-CBCT) imaging for patients of tongue malignancy treated without using tongue bite. Methods: We analysed 100 KV-cone beam CTs performed on 10 patients with carcinoma of tongue undergoing fractionated radiotherapy. All the patients underwent thermoplastic mask immobilisation and CT simulation. During the course of radiotherapy, all patients underwent volumetric KV-CBCT imaging to assess the movements of tongue. Five arbitrary reference points were used to analyse the movements of tongue in 3-dimensions: 1) Point A: Tip of tongue; 2) Point B: Point over right lateral border, 4 cm posterior to the tip of tongue; 3) Point C: Point over left lateral border, 4 cm posterior to the tip of tongue; 4) Point D: Point over superior most part (dorsum) of tongue, 4 cm posterior to the tip of tongue; 5) Point E: Point over the surface of base of tongue at the level of tip of epiglottis. Results: Mean movements of point A: +0.21 cm (SD: 0.12) and -0.23 cm (SD: 0.14), point B: +0.14 cm (SD: 0.04) and -0.19 cm (SD: 0.1), point C: +0.12 cm (SD: 0.05) and -0.14 cm (SD: 0.06), point D: +0.15 cm (SD: 0.07) and -0.29 cm (SD: 0.22) and point E: +0.23 cm (SD: 0.15) and -0.23 cm (SD: 0.14). Conclusion: Organ movement is one of the great challenges encountered during radiotherapy. Tongue is one such organ in head and neck region. Concept of internal target volume (ITV) margin which takes into account the internal organ movements should be considered for tongue malignancies. ITV to PTV margin will depend on the setup accuracy, immobilization device and imaging modality utilised for setup verification. In an IGRT (Image Guided Radio Therapy) setup, a PTV margin of 0.3 to 0.5 cm from ITV would be safe

Derivation of equations to define inflection point and its analysis in flattening filter free photon beams based on the principle of polynomial function

Purpose: The objective of this work is to (1) present a mechanism for calculating inflection points on profiles at various depths and field sizes, and (2) study the doses at the inflection points for various field sizes at depth of maximum dose (Dmax) for flattening filter free (FFF) photon beam profiles. Methods: Graphical representation was done on percentage of dose versus inflection points. Also, using the polynomial function, the author formulated equations for calculating spot-on inflection point on the profiles for both the 6MV and 10 MV energies for different field sizes at various depths. Results: In a 10 MV FFF radiation beam, the dose at inflection point of the profile decreases as the field size increases. However, in 6MV FFF radiation beam, the dose at the inflection point initially increases with an increase in the field size up to 10 ×10 cm2 and decreases after 10 ×10 cm2. The polynomial function was fitted for both the 6 MV and 10 MV FFF beams for all field sizes and depths. Conclusion: Polynomial function is one of the easiest ways of identifying the inflection point in FFF beam for various field sizes and depths. Graphical representation of dose versus inflection point for both FFF energies was derived.</p

Intensity modulated radiotherapy versus volumetric modulated arc therapy in breast cancer: A comparative dosimetric analysis

Purpose: Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) has the capacity to optimize the dose distribution. We analyzed the dosimetric differences of plans in treatment planning system (TPS) between VMAT and IMRT in treating breast cancer. Methods: Fourteen patients were simulated, planned, and treated with VMAT using single, double or partial arcs. IMRT treatments were generated using 4 to 5 tangential IMRT fields for the same patients. All treatment plans were planned for 50 Gy in 25 fractions. The VMAT and IMRT plans were compared using the planning target volume (PTV) dose and doses to the other organs at risk (OARs). Results: For the PTV, comparable minimum, mean, maximum, median, and modal dose as well equivalent sphere diameter of the structure (Equis) were observed between VMAT and IMRT plans and found that these values were significantly equal in both techniques. The right lung mean and modal doses were considerably higher in VMAT plans while maximum value was considerably lower when compared with IMRT plans. The left lung mean and modal doses were higher with VMAT while maximum doses were higher in IMRT plans. The mean dose to the heart and maximum dose to the spinal cord was lower with IMRT. The mean dose to the body was higher in VMAT plans while the maximum dose was higher in IMRT plans. Conclusion: Four field tangential IMRT delivered comparable PTV dose with generally less dose to normal tissues in our breast cancer treatment study. The IMRT plans typically had more favourable dose characteristics to the lung, heart, and spinal cord and body dose when compared with VMAT. The only minor advantage of VMAT for breast cases was slightly better PTV coverage.</p

Advantage of using deep inspiration breath hold with active breathing control and image-guided radiation therapy for patients treated with lung cancers

Purpose: The aim of this study was to evaluate the irradiated volume and doses to the target, heart, left lung, right lung and spinal cord, the number of segments and treatment time by using moderated deep inspiration breath hold (mDIBH) with active breathing control (ABC) and image-guided radiotherapy (IGRT) for patients treated with lung cancers.Methods: The suitability of this technique for lung patient treated with ABC was investigated and the solutions to achieve better treatments were discussed. Eleven lung cancer patients (3 left-sided and 8 right sided lesions) with stages I-III underwent standard free breath (FB) and ABC computed tomography (CT) scans in the treatment supine position. This can be achieved by applying respiratory manoeuvres, such as mDIBH, during which the threshold volume utilized is defined as 75-80% of the maximum aspiratory capacity. Five to seven, 6-MV photon beams with optimized gantry angles were designed according to the tumor location to conform to the PTV while sparing as much heart, spinal cord, and contra lateral lung as possible. For eleven patients, treatment planning using mDIBH CT data with intensity modulated radiation therapy (IMRT) was then reoptimized on the free breathing data set for comparison. The studied parameters of the plans for each patient were evaluated based on the average of the minimum, mean, and maximum difference in dose, the range of difference, and the p-value using two-tailed paired t test assuming equal variance.Results: The average volume of the planning target volume (PTV) in 11 patients increased to 1.32% in ABC compared to FB. The average volume of heart in 11 patients decreased to 2.9% in ABC compared to free breathing IMRT. In the case of lungs, the volume increased to 27.5% and 25.85% for left and right lungs, respectively. The range of mean difference in dose to the PTV in 11 patients was -54 cGy to 230 cGy with ABC technique when compared with free breathing. The range of mean dose difference of heart in 11 patients observed were -88 cGy to 66 cGy (p &lt; 0.0410) between ABC and FB. The range of maximum dose difference to the spinal cord in 11 patients were -1592 cGy to 190 cGy (p &lt; 0.041) with ABC technique when compared with FB IMRT. Monitor units (MUs) were -22.9% less in ABC compared to FB. Segments were more in ABC compared to FB for about 16.39% on an average. The average of minimum, mean and maximum difference in dose to the right lung and left lung were less in ABC compared with FB.Conclusion: In most of the cases, IGRT with ABC significantly reduces the mean dose to heart, right lung, left lung, and spinal cord compared with FB. Discrepancy observed in few cases made the statistical data inconsistent. Depending on anatomy and arbitrary phase of the breathing cycle, the results may vary and for better outcome of the results optimum treatment procedures need to follow.  </p