In-vitro investigation of out-of-field cell survival following the delivery of conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans

The aim of this work is to determine the out-of-field survival of cells irradiated with either the primary field or scattered radiation in the presence and absence of intercellular communication following delivery of conformal, IMRT and VMAT treatment plans. Single beam, conformal, IMRT and VMAT plans were created to deliver 3 Gy to half the area of a T80 flask containing either DU-145 or AGO-1522 cells allowing intercellular communication between the in-and out-of-field cell populations. The same plans were delivered to a similar custom made phantom used to hold two T25 culture flasks, one flask in-field and one out-of-field to allow comparison of cell survival responses when intercellular communication is physically inhibited. Plans were created for the delivery of 8 Gy to the more radio-resistant DU-145 cells only in the presence and absence of intercellular communication. Cell survival was determined by clonogenic assay. In both cell lines, the out-of-field survival was not statistically different between delivery techniques for either cell line or dose. There was however, a statistically significant difference between survival out-of-field when intercellular communication was intact (single T80 culture flask) or inhibited (multiple T25 culture flasks) to in-field for all plans. No statistically significant difference was observed in-field with or without cellular communication to out-of-field for all plans. These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields when cellular communication between differentially irradiated cell populations is present. This data is further evidence that refinement of existing radiobiological models to include indirect cell killing effects is required.

Improvement in clinical step and shoot intensity modulated radiation therapy delivery accuracy on an integrated linear accelerator control system

Purpose: The dose delivery accuracy of 30 clinical step and shoot intensity modulated radiation therapy plans was investigated using the single integrated multileaf collimator controller of the Varian Truebeam linear accelerator (linac) (Varian Medical Systems, Palo Alto, CA) and compared with the dose delivery accuracy on a previous generation Varian 2100CD C-Series linac.

Methods and Materials: Ten prostate, 10 prostate and pelvic node, and 10 head-and-neck cases were investigated in this study. Dose delivery accuracy on each linac was assessed using Farmer ionization chamber point dose measurements, 2-dimensional planar ionization chamber array measurements, and the corresponding Varian dynamic log files. Absolute point dose measurements, fluence delivery accuracy, leaf position accuracy, and the overshoot effect were assessed for each plan.

Results: Absolute point dose delivery accuracy increased by 1.5% on the Truebeam compared with the 2100CD linac. No improvement in fluence delivery accuracy between the linacs, at a gamma criterion of 3%/3 mm was measured using the 2-dimensional ionization chamber array, with median (interquartile range) gamma passing rates of 98.99% (97.70%-99.72%) and 99.28% (98.26%-99.75%) for the Truebeam and 2100CD linacs, respectively. Varian log files also showed no improvement in fluence delivery between the linacs at 3%/3 mm, with median gamma passing rates of 99.97% (99.93%-99.99%) and 99.98% (99.94%-100%) for the Truebeam and 2100CD linacs, respectively. However, log files revealed improved leaf position accuracy and fluence delivery at 1%/1 mm criterion on the Truebeam (99.87%; 99.78%-99.94%) compared with the 2100CD linac (97.87%; 91.93%-99.49%). The overshoot effect, characterized on the 2100CD linac, was not observed on the Truebeam.

Conclusions: The integrated multileaf collimator controller on the Varian Truebeam improves clinical treatment delivery accuracy of step and shoot intensity modulated radiation therapy fields compared with delivery on a Varian C-series linac. © 2014.

Inverse planned constant dose rate volumetric modulated arc therapy (VMAT) as an efficient alternative to five-field intensity modulated radiation therapy (IMRT) for prostate

Purpose: The aim of this work was to determine if volumetric modulated arc therapy (VMAT) plans, created for constant dose-rate (cdrVMAT) delivery are a viable alternative to step and shoot five-field intensity modulated radiation therapy (IMRT). Materials and methods: The cdrVMAT plans, inverse planned on a treatment planning system with no solution to account for couch top or rails, were created for delivery on a linear accelerator with no variable dose rate control system. A series of five-field IMRT and cdrVMAT plans were created using dual partial arcs (gantry rotating between 260° and 100°) with 4° control points for ten prostate patients with the average rectal constraint incrementally increased. Pareto fronts were compared for the planning target volume homogeneity and average rectal dose between the two techniques for each patient. Also investigated were tumour control probability and normal tissue complication probability values for each technique. The delivery parameters [monitor units (MU) and time] and delivery accuracy of the IMRT and VMAT plans were also compared. Results: Pareto fronts showed that the dual partial arc plans were superior to the five-field IMRT plans, particularly for the clinically acceptable plans where average rectal doses were less for rotational plans (p = 0·009) with no statistical difference in target homogeneity. The cdrVMAT plans had significantly more MU (p = 0·005) but the average delivery time was significantly less than the IMRT plans by 42%. All clinically acceptable cdrVMAT plans were accurate in their delivery (gamma 99·2 ± 1·1%, 3%3 mm criteria). Conclusions Accurate delivery of dual partial arc cdrVMAT avoiding the couch top and rails has been demonstrated.

Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

Evaluation of organ-specific peripheral doses after 2-dimensional, 3-dimensional and hybrid intensity modulated radiation therapy for breast cancer based on Monte Carlo and convolution/superposition algorithms: implications for secondary cancer risk assessment.

To make a comprehensive evaluation of organ-specific out-of-field doses using Monte Carlo (MC) simulations for different breast cancer irradiation techniques and to compare results with a commercial treatment planning system (TPS). Three breast radiotherapy techniques using 6MV tangential photon beams were compared: (a) 2DRT (open rectangular fields), (b) 3DCRT (conformal wedged fields), and (c) hybrid IMRT (open conformal+modulated fields). Over 35 organs were contoured in a whole-body CT scan and organ-specific dose distributions were determined with MC and the TPS. Large differences in out-of-field doses were observed between MC and TPS calculations, even for organs close to the target volume such as the heart, the lungs and the contralateral breast (up to 70% difference). MC simulations showed that a large fraction of the out-of-field dose comes from the out-of-field head scatter fluence (>40%) which is not adequately modeled by the TPS. Based on MC simulations, the 3DCRT technique using external wedges yielded significantly higher doses (up to a factor 4-5 in the pelvis) than the 2DRT and the hybrid IMRT techniques which yielded similar out-of-field doses. In sharp contrast to popular belief, the IMRT technique investigated here does not increase the out-of-field dose compared to conventional techniques and may offer the most optimal plan. The 3DCRT technique with external wedges yields the largest out-of-field doses. For accurate out-of-field dose assessment, a commercial TPS should not be used, even for organs near the target volume (contralateral breast, lungs, heart).

Bone markers and cytokines in response to low-impact, high-intensity exercise

A low-impact, high-intensity interval exercise (HIE) bout was used to determine whether an association exists between cytokines and bone turnover markers following an acute bout of exercise. Twenty-three recreationally active males (21.8±2.4yr) performed a single HIE bout on a cycle ergometer at 90% relative intensity. Venous blood samples were collected prior to exercise, 5-minutes, 1-hour, and 24-hours post-exercise, and were analyzed for serum levels of pro-inflammatory (IL-6, IL-1α, IL-1β, and TNF-α) and anti- inflammatory cytokines (IL-10) and markers of bone formation (BAP, OPG) and resorption (NTX, RANKL). Significant effects were observed with all bone markers, especially 5-minutes post-exercise with BAP, OPG, and RANKL increasing from baseline (p<0.05). Significant effects were also observed for IL-1α, IL-1β, IL-6, and TNF-α (p<0.00, p=0.04, p=0.03, p<0.00). In addition, post-exercise changes in NTX, BAP, and OPG were significantly correlated pro- and anti-inflammatory cytokines, suggesting that an interaction exists between the immune and skeletal response to exercise.

The Effects of Physical Fitness and Body Composition on Oxygen Consumption and Heart Rate Recovery After High-Intensity Exercise

The aim of this study was to investigate the potential relationship between excess post-exercise oxygen consumption (EPOC), heart rate recovery (HRR) and their respective time constants (tvo(2) and t(HR)) and body composition and aerobic fitness (VO(2)max) variables after an anaerobic effort. 14 professional cyclists (age = 28.4 +/- 4.8 years, height = 176.0 +/- 6.7 cm, body mass = 74.4 +/- 8.1 kg, VO(2)max = 66.8 +/- 7.6 mL. kg(-1) . min(-1)) were recruited. Each athlete made 3 visits to the laboratory with 24h between each visit. During the first visit, a total and segmental body composition assessment was carried out. During the second, the athletes undertook an incremental test to determine VO(2)max. In the final visit, EPOC (15-min) and HRR were measured after an all-out 30s Wingate test. The results showed that EPOC is positively associated with % body fat (r = 0.64), total body fat (r = 0.73), fat-free mass (r = 0.61) and lower limb fat-free mass (r = 0.55) and negatively associated with HRR (r = - 0.53, p < 0.05 for all). HRR had a significant negative correlation with total body fat and % body fat (r = - 0.62, r = - 0.56 respectively, p < 0.05 for all). These findings indicate that VO(2)max does not influence HRR or EPOC after high-intensity exercise. Even in short-term exercise, the major metabolic disturbance due to higher muscle mass and total muscle mass may increase EPOC. However, body fat impedes HRR and delays recovery of oxygen consumption after effort in highly trained athletes.

High-Intensity Resistance Training with Insufficient Recovery Time Between Bouts Induce Atrophy and Alterations in Myosin Heavy Chain Content in Rat Skeletal Muscle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effect of a previous high intensity running exercise on isokinetic muscular strength in individuals with different training backgrounds

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The Chemical Percolation Devolatilization Model Applied to the Devolatilization of Coal in High Intensity Acoustic Fields

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)