Combined effect of heterogeneous target dose and heterogeneous radiosensitivity on tumor control probability for different fractionation regimens.

PURPOSE: To evaluate the combined effect of heterogeneous target dose and heterogeneous radiosensitivity on tumor control probability (TCP) for different number of fractions (Nf). METHODS: The linear-quadratic (LQ) model is employed to study dependence of TCP on Nf under the condition of fixed nominal biologically effective dose (BEDnom). RESULTS: Formula for the optimum target dose which maximizes TCP under the condition BEDnom=const is analytically derived. It is shown that the dependence of TCP on Nfis non-monotonic. In addition, the dependence of TCP on Nf for different variances of the target dose and radiosensitivity of malignant cells is demonstrated by using numerical computations. CONCLUSIONS: It is shown that the optimum mean dose in the target is defined by the standard deviations of the target dose (σD) and standard deviations of parameters alpha (σα) and beta (σß). The findings of this study indicate that hypofractionated regimens for stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) with Nf⩽3 can be radiobiologically inferior to the regimens with five or more fractions.

Effect of heterogeneous target dose and radiosensitivity on BED and TCP for different treatment regimens.

Purpose.To evaluate how heterogeneity of the target dose and heterogeneity of intra-tumor radiosensitivity affect biologically effective dose (BED) and tumor control probability (TCP) depending on the number of fractions (Nf).Methods.The dependences of TCP and BED in the planning target volume onNfare studied using the linear-quadratic model. In the considered case, the nominal biologically effective dose(BEDnom)is fixed and the variances of the target dose (σD) and radiosensitivity (σα) are assumed to be small.Results.By using series expansion of the survival probability of malignant cells, it is analytically shown that for smallσDandσαboth BED and TCP increase with increasingNfunder the conditionBEDnom=const.In addition, the dependences of BED and TCP onNffor different values ofσDandσαare studied by using an analytical expression for BED in the case of Gaussian distributions of both target dose and radiosensitivity.Conclusions.Small variations in the absorbed dose and intratumor radiosensitivity can significantly reduce BED and TCP. The decreases in these quantities can be reduced by increasing the number of fractions. The findings of this study indicate that hypofractionated regimens withNf=20and dose per fractiond≤5Gy can lead to higher BED and TCP compared to treatment regimens withNf≤5andd≥10Gy commonly used for stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS).

Effect of reoxygenation on hypofractionated radiotherapy of prostate cancer.

PURPOSE: To assess the role of reoxygenation of hypoxic tumor cells in hypofractionated radiotherapy of prostate cancer. METHODS: The considered radiobiological model is based on the assumption of two populations (compartments) of cells: oxygenated (aerobic) cells and hypoxic cells. After each fraction of radiation, some of the hypoxic cells reoxygenate while a fraction of initially aerobic cells becomes hypoxic. The kinetics of this process between successive treatments is described by coupled, first-order differential equations. To determine the effect of reoxygenation on cell kill in the treatment target, we utilize the linear-quadratic (LQ) model assuming different radiosensitivities for the aerobic and hypoxic cells. RESULTS: Analytical solutions for the number of surviving malignant cells are obtained for special cases of slow and fast reoxygenation. The radiobiological effect of reoxygenation for different fractionation regimens is also evaluated numerically. CONCLUSIONS: In this study, a radiobiological model for kinetics of reoxygenation in tumors is used to evaluate different fractionation schedules in radiotherapy of prostate cancer. The obtained results indicate that in the case of low alpha/beta ratio for malignant cells (e.g., α / ß  = 1.5 Gy), treatment schedule with 4-10 fractions and dose per fraction >4-5 Gy can result in increased cell kill in the treatment target at the same level of rectal toxicity as compared to conventional fractionation. The findings of this study also suggest that radiotherapy of the prostate with 1-3 fractions can be radiobiologically inferior to treatments with greater number of fractions.

Differentiating between T1 and T2* changes caused by gadopentetate dimeglumine in the kidney by using a double-echo dynamic MR imaging sequence.

Dynamic MR images of the passage of gadopentetate dimeglumine through the kidneys of normal rats are obtained using a dual gradient-echo sequence. The amplitudes of gradient echoes are defined by local T1 and T2* values in the tissue. The ratio of these amplitudes, primarily defined by local T2*, can be used to differentiate between T1 and T2* effects. This is particularly important with regard to renal studies because, due to a highly inhomogeneous distribution of gadopentetate dimeglumine in the kidney, T2* shortening can impede MR data analysis. To study changes in the observed signal caused by gadopentetate dimeglumine, curves of MR renal intensity versus time were obtained in the cortex and medulla after administration of the contrast agent. Using T2* compensation, distinct temporal peaks were observed in the cortex and outer medulla, indicating a high concentration of gadopentetate dimeglumine in the vascular phase. The authors conclude that this technique can be a useful tool for studying renal function noninvasively.

Changes in T2*-weighted images during hyperoxia differentiate tumors from normal tissue.

Experiments were performed to determine whether changes in T2*-weighted MR images during and after hyperoxia differentiate tumors from normal tissue. Mammary adenocarcinomas implanted in the right hind limbs of rats were studied. Gradient echo images were obtained at 2 Tesla with an evolution time of 20 ms and a recycle time of 1 s. Breathing gas was either air or 100% O2. Significant increases in image intensity were observed in tumor centers and rims during hyperoxia while much smaller changes were detected in the surrounding muscle. The relaxation rate (1/T2*) in tumors decreased during hyperoxia by an average of 2.5 +/- 1.0 s-1, while in muscle the average change was an increase of 0.6 +/- 2.1 s-1. The largest decreases in relaxation rate were detected in non-necrotic tumor regions with relatively low density of blood vessels. Immediately following hyperoxia significant decreases in intensity were detected in tumors while much smaller decreases were detected in the surrounding muscle.

Magnetic resonance imaging of leiomyomata uteri: assessing therapy with the gonadotropin-releasing hormone agonist leuprolide.

Two cases are reported in which MRI was used to monitor the preoperative response of leiomyomata uteri to gonadotropin releasing hormone agonist therapy. The uterus was measured in the cephalocaudad, anterior-posterior, and transverse planes by MRI images. All uterine dimensions decreased in size after leuprolide therapy. One patient ultimately chose leuprolide therapy alone for control of her symptoms while a second patient had four myomas surgically removed after leuprolide therapy. MRI proved to be a good modality to monitor response to leuprolide therapy and assist in the management of these patients.