Hypo-fractionated boost in locally advanced non-small cell lung cancer: temporal distribution of boost fractions.

To propose new schemas for radiation boosting of primary tumors, in locally advanced non-small cell lung cancers (NSCLC), in conjunction with standard chemoradiotherapy. To investigate the effect of temporal distributions of the boost fractions on tumor control. NSCLC cases, previously treated with 60 Gy in 30 fractions, were retrospectively planned by adding a radiation boost (25 Gy in 5 fractions) to the primary tumor. Several integrated and sequential boosting schedules were considered. Biological doses were calculated for targets and organs at risk (OAR). Tumor control probabilities (TCP) were calculated using an empirical model and a stochastic model that accounts more systematically for tumor growth kinetics and cell kill. For heterogeneous patient populations, the TCPs for different boost schedules ranged from 82% to 84% and from 73% to 74% for integrated and sequential boosting respectively. For individual tumors with specific growth parameters, the TCP varied by up to 19% between the different schedules. The TCP for sequential boosting was expected to be up to 67% lower than front integrated boosting. The gap in TCP between schedules was higher for tumors with higher clonogenic cell numbers, lower radio-sensitivity, shorter doubling times and lower cell loss. The proposed boosting schemas are dosimetrically feasible and biologically effective. We suggest that the boosts are most effective when given during the first week of treatment and least effective when given sequentially after the end of treatment. The effect of boost scheduling and the effectiveness of front boosting are expected to be most significant for tumors with high clonogenic cell numbers, fast growing rates, low cell loss and low radio-sensitivity. Ultimately, animal studies and clinical trials, guided by biology modeling as presented in the present work, will be needed to verify the effectiveness of fine tuning temporal distributions of radiotherapy fractions.

Status of Low Birth Weight Babies in Mymensingh Medical College Hospital.

Low birth weight (LBW) is the major neonatal health problem in Bangladesh like other developing countries with limited resource. But only a few studies had done about status of LBW at hospital setting in this country. The objective of the study that to evaluate the status and immediate outcome of the LBW This cross sectional retrospective study was done in neonatal ward of Mymensingh medical college hospital. In this 1000 bedded tertiary care level teaching hospital only 40 cots and 10 open incubators are sanctioned but daily average admission in neonatal ward more than 30. On an average about 100 patients are remaining in the ward. Three or four patients are nursed in each cot. It covers the vast catchment's area of Bangladesh having more than two cores of population. With limited resources and manpower, this neonatal ward has to bear the burden of 100 neonates and daily admission of 30 neonates. Study period was one year (October 2013 to September 2014). Total admitted neonates were 8359. All admitted neonates were considered as study population and all LBW babies were considered as sample. Among total population 41% (3423) were LBW. Among total LBW babies maximum (80.7%) had birth weight 1500-2499gm followed by Very Low birth weight (VLBW) 1000 - 1499gm 14.7%, Extreme Low birth weight (ELBW) 1000-750gm 1.6% and Incredible low birth weight <750gm 1.7%. Term LBW (IUGR) babies were 52% and preterm LBW were 48%. Death rate among LBW babies group were higher (18.5%) than death rate (15.8%) among all admitted neonate. By comparison of mortality rate among different subgroup of LBW shows highest mortality (65.5%) was in incredible low birth weight babies group followed by ELBW group (58.8%) and among VLBW group 26.4% and lowest mortality (15.3%) was among birth weight 1500-2499gm group babies. Death rate was inversely related to birth weight. Death rate among preterm LBW babies (21.5%) was higher than Term LBW (IUGR) babies (15.7%). So, death rate was also inversely related to the maturity. Death rate among LBW babies is still higher in our institute than other developed institute of home and abroad. Death rate specially higher among incredible birth weight group and ELBW group in our institute. Further improvement in neonatal care is needed to decrease the mortality among LBW babies.

Development of a novel ArcCHECK(™) insert for routine quality assurance of VMAT delivery including dose calculation with inhomogeneities.

PURPOSE: To design a versatile, nonhomogeneous insert for the dose verification phantom ArcCHECK(™) (Sun Nuclear Corp., FL) and to demonstrate its usefulness for the verification of dose distributions in inhomogeneous media. As an example, we demonstrate it can be used clinically for routine quality assurance of two volumetric modulated arc therapy (VMAT) systems for lung stereotactic body radiation therapy (SBRT): SmartArc(®) (Pinnacle(3), Philips Radiation Oncology Systems, Fitchburg, WI) and RapidArc(®) (Eclipse(™), Varian Medical Systems, Palo Alto, CA). METHODS: The cylindrical detector array ArcCHECK(™) has a retractable homogeneous acrylic insert. In this work, we designed and manufactured a customized heterogeneous insert with densities that simulate soft tissue, lung, bone, and air. The insert offers several possible heterogeneity configurations and multiple locations for point dose measurements. SmartArc(®) and RapidArc(®) plans for lung SBRT were generated and copied to ArcCHECK(™) for each inhomogeneity configuration. Dose delivery was done on a Varian 2100 ix linac. The evaluation of dose distributions was based on gamma analysis of the diode measurements and point doses measurements at different positions near the inhomogeneities. RESULTS: The insert was successfully manufactured and tested with different measurements of VMAT plans. Dose distributions measured with the homogeneous insert showed gamma passing rates similar to our clinical results (∼99%) for both treatment-planning systems. Using nonhomogeneous inserts decreased the passing rates by up to 3.6% in the examples studied. Overall, SmartArc(®) plans showed better gamma passing rates for nonhomogeneous measurements. The discrepancy between calculated and measured point doses was increased up to 6.5% for the nonhomogeneous insert depending on the inhomogeneity configuration and measurement location. SmartArc(®) and RapidArc(®) plans had similar plan quality but RapidArc(®) plans had significantly higher monitor units (up to 70%). CONCLUSIONS: A versatile, nonhomogeneous insert was developed for ArcCHECK(™) for an easy and quick evaluation of dose calculations with nonhomogeneous media and for comparison of different treatment planning systems. The device was tested for SmartArc(®) and RapidArc(®) plans for lung SBRT, showing the uncertainties of dose calculations with inhomogeneities. The new insert combines the convenience of the ArcCHECK(™) and the possibility of assessing dose distributions in inhomogeneous media.

Poster - Thur Eve - 08: A1SL ion chamber charged particle disequilibrium corrections for lung dose measurements using Monte Carlo.

An in house inhomogeneous insert for use with ArcCHECK ™ was developed for dose calculation verification of Stereotactic Body Radiation Therapy (SBRT) lung plans. The inhomogeneous insert has various ion chamber inserts for different geometrical configurations (lung, soft tissue, bone, air). However, the insertion of an ion chamber in a low density medium perturbs the dose to that region by creating Charged Particle Disequilibrium (CPD), limiting the accuracy of ion chamber measurements. By simulating the ion chamber and phantom using Monte Carlo, a correction factor could be calculated and measured to verify the dose difference caused by CPD. BEAMnrc was used to generate a phase space input file for DOSXYZnrc with beam characteristics that matched clinical commissioning data. A model of the A1SL ion chamber geometry (shell, collector, stem, guard) was simulated in a simple water-lung-water slab phantom. Dose to the active area of the ion chamber was measured in several locations throughout the phantom. The active area of the ion chamber was replaced by the surrounding medium; i.e., water or lung within the phantom, and the dose to the same voxels was calculated. The dose was measured on a Linac and the results agreed within 3% and confirmed that the presence of the ion chamber in low density lung perturbs the dose measured in the field by over 31%.

Poster - Thur Eve - 64: Evaluation of SmartArc and RapidArc for lung SBRT treatment planning and delivery.

OBJECTIVES: To evaluate the performance of RapidArc® (Eclipse 10.0.28) and SmartArc® (Pinnacle 9.0) radiotherapy plans for lung stereotactic body radiation therapy (SBRT) in terms of dosimetric plan quality, delivery efficiency, inhomogeneity corrections and accuracy of dose delivery using a custom-built heterogeneity insert for ArcCHECK™ (Sun Nuclear Corp., FL, USA). METHODS: SmartArc® and RapidArc® plans were generated for 10 patients. The quality of the plans was evaluated in terms of conformity indices (R100 and R50 ) and the dose to the organs at risk. The efficiency was evaluated in terms of the monitor units (MUs) required for a given prescription dose. For dose verification, we designed and manufactured a heterogeneity insert for ArcCHECK™ with densities that simulate soft tissue, lung, bone, and air and having multiple locations for point dose measurements. Accuracy of dose delivery was assessed using gamma analysis. RESULTS: The overall plan quality was similar when comparing SmartArc® with RapidArc®. However, RapidArc® plans required significantly more MUs-up to 72%™compared with SmartArc® plans (p<0.001). ArcCHECK™ measurements in the presence of inhomogeneities showed better agreement for SmartArc® plans. CONCLUSION: Plan quality for SmartArc® and RapidArc® was comparable. However, SmartArc® plans were more efficient, requiring significantly fewer monitor units, and were delivered more accurately in a non-homogeneous phantom. With the custom-built heterogeneity insert, ArcCHECK™ can be used efficiently to verify inhomogeneity corrections and dose delivery accuracy for lung SBRT plans.

Incorporation of microdosimetric concepts into a biologically-based model of radiation carcinogenesis.

The generalised state-vector model of radiation carcinogenesis (SVM) simulates radiation induced biological effects by expressing the transition rates between the various initiation and promotion stages in terms of dose rate for low and high linear energy transfer (LET) particles. In the present work, the SVM has been reformulated to incorporate single track characteristics of particles with varying LET. Transition rates of the initiation phase were expressed as functions of LET by describing the complexity and clustering of DNA double strand breaks (DSBs) and its effect on repair kinetics, while the promotion phase was reformulated based on a multi-target single-hit hypothesis. Such an approach allows the consideration of hit frequencies and the variability of the specific energy and LET spectra of radon progeny alpha particles in bronchial target cells for different exposure conditions.

Modelling the effect of non-uniform radon progeny activities on transformation frequencies in human bronchial airways.

The effects of radiological and morphological source heterogeneities in straight and Y-shaped bronchial airways on hit frequencies and microdosimetric quantities in epithelial cells have been investigated previously. The goal of the present study is to relate these physical quantities to transformation frequencies in sensitive target cells and to radon-induced lung cancer risk. Based on an effect-specific track length model, computed linear energy transfer (LET) spectra were converted to corresponding transformation frequencies for different activity distributions and source-target configurations. Average transformation probabilities were considerably enhanced for radon progeny accumulations and target cells at the carinal ridge, relative to uniform activity distributions and target cells located along the curved and straight airway portions at the same exposure level. Although uncorrelated transformation probabilities produce a linear dose-effect relationship, correlated transformations first increase depending on the LET, but then decrease significantly when exceeding a defined number of hits or cumulative exposure level.

Modeling lung cancer incidence in rats following exposure to radon progeny.

Lung cancer incidence in Sprague-Dawley rats was simulated by a biologically based carcinogenesis model, which is formulated mathematically in terms of a stochastic state-vector model. Doses to the sensitive target cells in the bronchial epithelium of the rat lung were calculated by a stochastic dosimetry model, considering the distinct monopodial branching structure and the crossfire of alpha particles from alveolar tissue to bronchial epithelium. Bronchial and alveolar cellular doses could reasonably be approximated by lognormal distributions, with geometric standard deviations (GSD) between 7 and 10, depending on exposure conditions. Based on a dose-exposure conversion factor of 8.5 mGy WLM(-1) and a GSD of 8, lung cancer incidences were calculated for each cumulative exposure category in the rat inhalation study, consisting of different exposure rates and exposure times. The fair agreement between theoretical predictions and experimental data over the whole exposure range emphasises the necessity to incorporate the full cellular dose distributions rather than their mean values.

Microdosimetry of radon progeny alpha particles in bronchial airway bifurcations.

A Monte Carlo code, initially developed for the calculation of microdosimetric spectra for alpha particles in cylindrical airways, has been extended to allow the computation of microdosimetric parameters for multiple source-target configurations in bronchial airway bifurcations. The objective of the present study was to investigate the effects of uniform and non-uniform radon progeny surface activity distributions in symmetric and asymmetric bronchial airway bifurcations on absorbed dose, hit frequency, lineal energy, single hit specific energy and LET spectra. In order to assess the effects of multiple hits, dose-dependent specific energy spectra were calculated by solving the compound Poisson process by iterative convolution. While the simulations showed significant differences of cellular dose quantities at different cell locations for uniformly distributed surface activities, even higher variations, as high as several orders of magnitude, were observed for non-uniform surface activity distributions, depending on the location of the cell and the local activity distribution.

Microdosimetry of inhomogeneous radon progeny distributions in bronchial airways.

A Monte Carlo code, initially developed for the calculation of microdosimetric spectra for alpha particles in cylindrical airways, has been extended to allow the computation (i) of additional microdosimetric parameters and (ii) for realistic exposure conditions in human bronchial airways with respect to surface activity distribution and airway geometry. The objective of the present study was to investigate the effects of non-uniform distributions of radon progeny activities in bronchial airways on cellular energy deposition parameters. Significant variations of hit frequencies, doses and microscopic energy deposition patterns were observed for epithelial cell nuclei, depending strongly on the assumed activity distributions. Thus, epithelial cells located at different positions in a given bronchial airway may experience a wide range of biological responses. The results obtained suggest that the hit frequency may be the primary physical parameter for alpha particles, supplemented by microdosimetric single event spectra, to be related to biological effects for chronic low level exposures.

Interaction of alpha particles at the cellular level--implications for the radiation weighting factor.

Since low dose effects of alpha particles are produced by cellular hits in a relatively small fraction of exposed cells, the present study focuses on alpha particle interactions in bronchial epithelial cells following exposure to inhaled radon progeny. A computer code was developed for the calculation of microdosimetric spectra, dose and hit probabilities for alpha particles emitted from uniform and non-uniform source distributions in cylindrical and Y-shaped bronchial airway geometries. Activity accumulations at the dividing spur of bronchial airway bifurcations produce hot spots of cellular hits, indicating that a small fraction of cells located at such sites may receive substantially higher doses. While presently available data on in vitro transformation frequencies suggest that the relative biological effectiveness for alpha particles ranges from about 3 to 10, the effect of inhomogeneous activity distributions of radon progeny may slightly increase the radiation weighting factor relative to a uniform distribution. Thus a radiation weighting factor of about 10 may be more realistic than the current value of 20, at least for lung cancer risk following inhalation of short-lived radon progeny.

Energy deposition, cellular radiation effects and lung cancer risk by radon progeny alpha particles.

Slowing down spectra, LET spectra, hit probabilities, and radiation doses were simulated for the interaction of single 218Po and 214Po alpha particles with sensitive basal and secretory cell nuclei in the bronchial epithelium of human and rat lungs for defined exposure conditions. Probabilities per unit track length for transformation, derived from in vitro experiments with C3H 10T1/2 cells, were used to estimate transformation probabilities for randon progeny alpha particles in basal and secretory cells. Different weighting schemes were assumed to relate cellular hit probabilities, doses and transformation probabilities, obtained for different cell depths and airway generations, to lung cancer risk per unit exposure. In vitro transformation and in vivo lung cancer incidence were simulated by a state-vector model which provides a stochastic formulation of dose-rate dependent cellular transitions related to formation of double strand breaks, repair, inactivation, stimulated mitosis and promotion through loss of intercellular communication.