Biological effectiveness of uniform and nonuniform dose distributions in radiotherapy for tumors with intermediate oxygen levels.

. We propose a criterion of biological effectiveness of nonuniform hypoxia-targeted dose distributions in heterogeneous hypoxic tumors based on equivalent uniform aerobic dose (EUAD). We demonstrate the utility of this criterion by applying it to the model problems in radiotherapy for tumors with different levels of oxygen enhancement ratio (OER) and different degrees of dose nonuniformity.

Equivalent uniform aerobic dose in radiotherapy for hypoxic tumors.

Equivalent uniform aerobic dose (EUAD) is proposed for comparison of integrated cell survival in tumors with different distributions of hypoxia and radiation dose.The EUAD assumes that for any non-uniform distributions of radiation dose and oxygen enhancement ratio (OER) within a tumor, there is a uniform distribution of radiation dose under hypothetical aerobic conditions with OER = 1 that produces equal integrated survival of clonogenic cells. This definition of EUAD has several advantages.

Equivalent uniform RBE-weighted dose in eye plaque brachytherapy.

Background: Brachytherapy for ocular melanoma is based on the application of eye plaques with different spatial dose nonuniformity, time-dependent dose rates and relative biological effectiveness (RBE).

Purpose: We propose a parameter called the equivalent uniform RBE-weighted dose (EUD) that can be used for quantitative characterization of integrated cell survival in radiotherapy modalities with the variable RBE, dose nonuniformity and dose rate. The EUD is applied to brachytherapy with I eye plaques designed by the Collaborative Ocular Melanoma Study (COMS).

Tumor control probability in hypofractionated radiotherapy as a function of total and hypoxic tumor volumes.

Clinical studies in the hypofractionated stereotactic body radiotherapy (SBRT) have shown a reduction in the probability of local tumor control with increasing initial tumor volume. In our earlier work, we obtained and tested an analytical dependence of the tumor control probability (TCP) on the total and hypoxic tumor volumes using conventional radiotherapy model with the linear-quadratic (LQ) cell survival. In this work, this approach is further refined and tested against clinical observations for hypofractionated radiotherapy treatment schedules.

Volume dependence in hypoxia-targeted dose escalation.

Purpose: Dose painting techniques based on dose escalation to hypoxic regions are usually governed by the spatial distribution of Oxygen Enhancement Ratio (OER) derived from PET or MRI images. The goal of this article is to show that the volume of the hypoxic region is also a parameter which may affect the radiobiological effectiveness of hypoxia-targeted dose escalation.

Methods: Our analysis is performed using the equation for Tumor Control Probability (TCP) derived from Poisson statistics.

Theoretical effectiveness of cell survival in fractionated radiotherapy with hypoxia-targeted dose escalation.

Purpose: The goal of this article is to compute the cell survival during fractionated radiotherapy with non-uniform hypoxia-targeted dose distribution relative to cell survival for a uniform dose distribution with equal integral tumor dose. The analysis is performed for different parameters of radiotherapy with conventional and hypofractionated dose regimens.

Methods: Our analysis is done using a parsimonious tumor response model that describes the major components of tumor response to radiotherapy such as radiosensitivity, cell proliferation, and hypoxia using as few variables as possible.

Assessment of interpatient heterogeneity in tumor radiosensitivity for nonsmall cell lung cancer using tumor-volume variation data.

Purpose: In our previous work, the authors showed that a distribution of cell surviving fractions S2 in a heterogeneous group of patients could be derived from tumor-volume variation curves during radiotherapy for head and neck cancer. In this research study, the authors show that this algorithm can be applied to other tumors, specifically in nonsmall cell lung cancer. This new application includes larger patient volumes and includes comparison of data sets obtained at independent institutions.

Tumor response parameters for head and neck cancer derived from tumor-volume variation during radiation therapy.

Purpose: The main goal of this paper is to reconstruct a distribution of cell survival fractions from tumor-volume variation for a heterogeneous group of head and neck cancer patients and compare this distribution to the data from predictive assays.

Methods: To characterize the tumor-volume variation during radiation therapy treatment, the authors use a two-level tumor-volume model of cell population that separates the entire tumor cell population into two subpopulations of viable cells and lethally damaged cells. This parameterized radiobiological model is integrated with a least squares objective function and a simulated annealing optimization algorithm to describe time-dependent tumor-volume variation rates in individual patients.

Evaluation of kV cone-beam ct performance for prostate IGRT: a comparison of automatic grey-value alignment to implanted fiducial-marker alignment.

Purpose: Cone-beam computed tomography (CBCT) is a new image-guided radiation therapy (IGRT) technique for patient alignment in radiotherapy. The CBCT x-ray volume imaging system from Elekta allows for a variety of alignment methods. The aim of this study is to assess the accuracy of soft-tissue-based automatic alignment as compared with manual alignment using intraprostatic fiducials.

The influence of CT image noise on proton range calculation in radiotherapy planning.

The purpose of this note is to evaluate the relationship between the stochastic errors in CT numbers and the standard deviation of the computed proton beam range in radiotherapy planning. The stochastic voxel-to-voxel variation in CT numbers called 'noise,' may be due to signal registration, processing and numerical image reconstruction technique. Noise in CT images may cause a deviation in the computed proton range from the physical proton range, even assuming that the error due to CT number-stopping power calibration is removed.

Tumor-volume simulation during radiotherapy for head-and-neck cancer using a four-level cell population model.

Purpose: To develop a fast computational radiobiologic model for quantitative analysis of tumor volume during fractionated radiotherapy. The tumor-volume model can be useful for optimizing image-guidance protocols and four-dimensional treatment simulations in proton therapy that is highly sensitive to physiologic changes.

Methods: The analysis is performed using two approximations: (1) tumor volume is a linear function of total cell number and (2) tumor-cell population is separated into four subpopulations: oxygenated viable cells, oxygenated lethally damaged cells, hypoxic viable cells, and hypoxic lethally damaged cells.

Time-dependent cell disintegration kinetics in lung tumors after irradiation.

We study the time-dependent disintegration kinetics of tumor cells that did not survive radiotherapy treatment. To evaluate the cell disintegration rate after irradiation, we studied the volume changes of solitary lung tumors after stereotactic radiotherapy. The analysis is performed using two approximations: (1) tumor volume is a linear function of the total cell number in the tumor and (2) the cell disintegration rate is governed by the exponential decay with constant risk, which is defined by the initial cell number and a half-life T(1/2).

Optimization of equivalent uniform dose using the L-curve criterion.

Optimization of equivalent uniform dose (EUD) in inverse planning for intensity-modulated radiation therapy (IMRT) prevents variation in radiobiological effect between different radiotherapy treatment plans, which is due to variation in the pattern of dose nonuniformity. For instance, the survival fraction of clonogens would be consistent with the prescription when the optimized EUD is equal to the prescribed EUD. One of the problems in the practical implementation of this approach is that the spatial dose distribution in EUD-based inverse planning would be underdetermined because an unlimited number of nonuniform dose distributions can be computed for a prescribed value of EUD.

Reconstruction of electron spectra from depth doses with adaptive regularization.

Electron spectral reconstruction of medical accelerators from measured depth doses is a practical method for providing the input initial phase space distribution at the patient surface that is required by Monte Carlo treatment planning systems. The posed inverse problem of spectral reconstruction is ill conditioned and this may lead to nonphysical oscillations in the reconstructed spectra. Use of a variational method of solution with a regularization technique removes the oscillations but tends to smooth the sharp (deltalike) energy peak that is a common feature in electron spectra generated by medical accelerators.

L-curve analysis of radiotherapy optimization problems.

We attempt to select an optimal value of regularization parameter in the optimization problems for intensity-modulated radiotherapy which are solved using a variational regularization technique. We apply to inverse treatment planning the L-curve method which was developed to determine the regularization parameter in the discrete ill-posed problems. The L-curve method is based on finding the regularization parameter which minimizes the residual norm which is a measure of accuracy of fit and the solution norm which is a measure of smoothness of solution.

Regularization of inverse planning for intensity-modulated radiotherapy.

The performance of a variational regularization technique to improve robustness of inverse treatment planning for intensity modulated radiotherapy is analyzed and tested. Inverse treatment planning is based on the numerical solutions to the Fredholm integral equation of the first kind which is ill-posed. Therefore, a fundamental problem with inverse treatment planning is that it may exhibit instabilities manifested in nonphysical oscillations in the beam intensity functions.

Angular correction in reconstruction of electron spectra from depth dose distributions.

Techniques for reconstruction of electron spectra from the depth-dose curves used to date have ignored the angular distribution of incident electrons scattered at large angles. The approximation adopted is to employ a database of monoenergetic depth-dose curves generated for normal incidence of electrons at the surface. This approximation is acceptable for direct electrons with small angular spread.

Reconstruction of electron spectra using singular component decomposition.

Reconstruction of electron spectra of medical accelerators from measured depth dose distributions is an attractive tool for commissioning of a Monte Carlo treatment planning system. However, the reconstruction method is an inverse radiation transport problem which is poorly conditioned, in the sense it may become unstable due to small perturbations in the input data. Predicting the sharp (delta-like) peak in the electron spectrum provides an additional challenge for the numerical reconstruction technique.

Intensity and energy modulated radiotherapy with proton beams: variables affecting optimal prostate plan.

Inverse planning for intensity- and energy-modulated radiotherapy (IEMRT) with proton beams involves the selection of (i) the relative importance factors to control the relative importance of the target and sensitive structures, (ii) an appropriate energy resolution to achieve an acceptable depth modulation, (iii) an appropriate beamlet width to modulate the beam laterally, and (iv) a sufficient number of beams and their orientations. In this article we investigate the influence of these variables on the optimized dose distribution of a simulated prostate cancer IEMRT treatment. Good dose conformation for this prostate case was achieved using a constellation of I factors for the target, rectum, bladder, and normal tissues of 500, 50, 15, and 1, respectively.