Biomedical subjects

B Gino Fallone

Publications and source records attributed to B Gino Fallone.

7 recordsLinked to original sources

PubMed2006

Fundamental form of a population TCP model in the limit of large heterogeneity.

A population tumor control probability (TCP) model for fractionated external beam radiotherapy, based on Poisson statistics and in the limit of large parameter heterogeneity, is studied. A reduction of a general eight-parameter TCP equation, which incorporates heterogeneity in parameters characterizing linear-quadratic radiosensitivity, repopulation, and clonogen number, to an equation with four parameters is obtained. The four parameters represent the mean and standard deviation for both clonogen number and a generalized radiosensitivity that includes linear-quadratic and repopulation descriptors. Further, owing to parameter inter-relationship, it is possible to express these four parameters as three ratios of parameters in the large heterogeneity limit. These ratios can be directly linked to two defining features of the TCP dose response: D50 and gamma50. In the general case, the TCP model can be written in terms of D50, gamma50 and a third parameter indicating the ratio of the levels of heterogeneity in clonogen number and generalized radiosensitivity; however, the third parameter is unnecessary when either of these two sources of heterogeneity is dominant. It is shown that heterogeneity in clonogen number will have little impact on the TCP formula for clinical scenarios, and thus it will generally be the case that the fundamental form of the Poisson-based population TCP model can be specified completely in terms of D50 and gamma50: TCP= 1/2 erfc[square root of pi(gamma50)(D50/D-1)]. This implies that limited radiobiological information can be determined by the analysis of dose response data: information about parameter ratios can be ascertained, but knowledge of absolute values for the fundamental radiobiological parameters will require independent auxiliary measurements.

Journal Article↗

PubMed2006

Reverse mapping of normal tissue complication probabilities onto dose volume histogram space: the problem of randomness of the dose volume histogram sampling.

A very important issue in contemporary inverse treatment radiotherapy planning is the specification of proper dose-volume constraints limiting the treatment planning algorithm from delivering high doses to the normal tissue surrounding the tumor. Recently we have proposed a method called reverse mapping of normal tissue complication probabilities (NTCP) onto dose-volume histogram (DVH) space, which allows the calculation of appropriate biologically based dose-volume constraints to be used in the inverse treatment planning. The method of reverse mapping requires random sampling from the functional space of all monotonically decreasing functions in the unit square. We develop, in this paper, a random function generator for the purpose of the reverse mapping. Since the proposed generator is based on the theory of random walk, it is therefore designated in this work, as a random walk DVH generator. It is theoretically determined that the distribution of the number of monotonically decreasing functions passing through a point in the dose volume histogram space follows the hypergeometric distribution. The proposed random walk DVH generator thus simulates, in a random fashion, trajectories of monotonically decreasing functions (finite series) that are situated in the unit square [0, 1] X [1,0] using the hypergeometric distribution. The DVH generator is an important tool in the study of reverse NTCP mapping for the calculation of biologically based dose-volume constraints for inverse treatment planning.

Computer Simulation↗

PubMed2006

A theoretical approach to the problem of dose-volume constraint estimation and their impact on the dose-volume histogram selection.

This paper outlines a theoretical approach to the problem of estimating and choosing dose-volume constraints. Following this approach, a method of choosing dose-volume constraints based on biological criteria is proposed. This method is called "reverse normal tissue complication probability (NTCP) mapping into dose-volume space" and may be used as a general guidance to the problem of dose-volume constraint estimation. Dose-volume histograms (DVHs) are randomly simulated, and those resulting in clinically acceptable levels of complication, such as NTCP of 5 +/- 0.5%, are selected and averaged producing a mean DVH that is proven to result in the same level of NTCP. The points from the averaged DVH are proposed to serve as physical dose-volume constraints. The population-based critical volume and Lyman NTCP models with parameter sets taken from literature sources were used for the NTCP estimation. The impact of the prescribed value of the maximum dose to the organ, D(max), on the averaged DVH and the dose-volume constraint points is investigated. Constraint points for 16 organs are calculated. The impact of the number of constraints to be fulfilled based on the likelihood that a DVH satisfying them will result in an acceptable NTCP is also investigated. It is theoretically proven that the radiation treatment optimization based on physical objective functions can sufficiently well restrict the dose to the organs at risk, resulting in sufficiently low NTCP values through the employment of several appropriate dose-volume constraints. At the same time, the pure physical approach to optimization is self-restrictive due to the preassignment of acceptable NTCP levels thus excluding possible better solutions to the problem.

Computer Simulation↗

PubMed2005

Comparing step-and-shoot IMRT with dynamic helical tomotherapy IMRT plans for head-and-neck cancer.

PURPOSE: The goal of this planning study was to compare step-and-shoot intensity-modulated radiotherapy (IMRT) plans with helical dynamic IMRT plans for oropharynx patients on the basis of dose distribution. METHODS AND MATERIALS: Five patients with oropharynx cancer had been previously treated by step-and-shoot IMRT at the University Medical Centre Utrecht, The Netherlands, applying five fields and approximately 60-90 segments. Inverse planning was carried out using Plato, version 2.6.2. For each patient, an inverse IMRT plan was also made using Tomotherapy Hi-Art System, version 2.0, and using the same targets and optimization goals. Statistical analysis was performed by a paired t test. RESULTS: All tomotherapy plans compared favorably with the step-and-shoot plans regarding sparing of the organs at risk and keeping an equivalent target dose homogeneity. Tomotherapy plans in particular realized sharper dose gradients compared with the step-and-shoot plans. The mean dose to all parotid glands (n = 10) decreased on average 6.5 Gy (range, -4 to 14; p = 0.002). The theoretical reduction in normal tissue complication probabilities in favor of the tomotherapy plans depended on the parotid normal tissue complication probability model used (range, -3% to 32%). CONCLUSION: Helical tomotherapy IMRT plans realized sharper dose gradients compared with the clinically applied step-and shoot plans. They are expected to be able to reduce the parotid normal tissue complication probability further, keeping a similar target dose homogeneity.

Head and Neck Neoplasms↗

PubMed2004

Phenomenologic model describing flow reduction for parotid gland irradiation with intensity-modulated radiotherapy: evidence of significant recovery effect.

OBJECTIVE: To develop a model describing the relationship between the parotid gland radiation dose and salivary flow reduction. Salivary function was described by the "relative flow reduction" (RFR)-a continuous variable in contrast to the traditional binary response used in normal tissue complication probability estimations. METHODS AND MATERIALS: Twenty-three patients with squamous cell carcinoma of the head and neck who were treated with intensity-modulated radiotherapy (RT) were the subject of this study. Of these patients, 19 had sufficiently long follow-up to be eligible for analysis. All were treated with curative intent, most (14 of 19) in the postoperative setting. The planning objectives were to deliver a mean dose of 50, 60, or 70 Gy, respectively, to low-risk microscopic, high-risk microscopic, and gross disease areas, while maintaining a mean dose of < or =20 Gy to the spared portion of one or both parotid glands. The mean dose to all parotid glands (right and left) was 30.2 Gy. All submandibular glands received >50 Gy when not surgically removed. Whole-mouth saliva collections, including both stimulated and unstimulated saliva flow, were obtained before treatment and at regular intervals after RT. These measurements were converted to the RFR by comparing the posttreatment and pretreatment flow rates. Any follow-up flow rates greater than baseline were scored as 0 relative reduction. We used Lyman's model to relate the equivalent uniform dose to RFR at various points for each patient. The equivalent uniform dose was calculated using the linear quadratic model, with an assumed alpha/beta ratio of 3 Gy for the parotid gland. Measurements were modeled 1-3 months after RT (early) and >6 months after RT (late), and using the best and worst measurements, regardless of when measured. RESULTS: Fitting the Lyman model to RFR data of unstimulated flow revealed a statistically significant dose-complication relationship. We observed a stepwise reduction in flow, with the threshold dose D(50) at 2 Gy per fraction (D(50)) increasing from 12.4 Gy (early) to 43.9 Gy (late). For the worst and best flow measurements, the corresponding D(50) (2 Gy/fr) was 13.0 Gy and 40.1 Gy, respectively. For most stimulated flow measurements, a weak relationship was found between the RFR and equivalent uniform dose. In those cases, the model did not yield a statistically significant description of the data. However, in the case of late measurements, the relationship was statistically significant and similar to that seen in the unstimulated cases, with a D(50) (2 Gy/fr) of 47.5 Gy. CONCLUSION: We observed a strong relationship between the generalized mean parotid gland dose and RFR. The threshold dose increased markedly between the early and late measurements, indicating a statistically significant recovery effect in this tissue. Compared with unstimulated flow, the RFR for stimulated flow was not described as well by the model, because the effect of the stimulant was not included in the model.

Carcinoma, Squamous Cell↗

PubMed2004

A TCP-NTCP estimation module using DVHs and known radiobiological models and parameter sets.

Radiotherapy treatment plan evaluation relies on an implicit estimation of the tumor control probability (TCP) and normal tissue complication probability (NTCP) arising from a given dose distribution. A potential application of radiobiological modeling to radiotherapy is the ranking of treatment plans via a more explicit determination of TCP and NTCP values. Although the limited predictive capabilities of current radiobiological models prevent their use as a primary evaluative tool, radiobiological modeling predictions may still be a valuable complement to clinical experience. A convenient computational module has been developed for estimating the TCP and the NTCP arising from a dose distribution calculated by a treatment planning system, and characterized by differential (frequency) dose-volume histograms (DDVHs). The radiobiological models included in the module are sigmoidal dose response and Critical Volume NTCP models, a Poisson TCP model, and a TCP model incorporating radiobiological parameters describing linear-quadratic cell kill and repopulation. A number of sets of parameter values for the different models have been gathered in databases. The estimated parameters characterize the radiation response of several different normal tissues and tumor types. The system also allows input and storage of parameters by the user, which is particularly useful because of the rapidly increasing number of parameter estimates available in the literature. Potential applications of the system include the following: comparing radiobiological predictions of outcome for different treatment plans or types of treatment; comparing the number of observed outcomes for a cohort of patient DVHs to the predicted number of outcomes based on different models/parameter sets; and testing of the sensitivity of model predictions to uncertainties in the parameter values. The module thus helps to amalgamate and make more accessible current radiobiological modeling knowledge, and may serve as a useful aid in the prospective and retrospective analysis of radiotherapy treatment plans.

Body Burden↗

PubMed2003

Beta dose-rate distributions in microscopic spherical tumors for intraperitoneal radioimmunotherapy.

PURPOSE: This work was designed to calculate the radial beta dose-rate profiles through microscopic spherical tumors. Its application is in the treatment of micrometastases in the peritoneal cavity by the intraperitoneal administration of radiolabeled immunoliposomes. METHODS AND MATERIALS: Using previously published data for the dose-rate as a function of distance from a point source of activity, dose-rate profiles through five sizes of tumors (radii: 10 microm, 50 microm, 100 microm, 500 microm, 1 mm) for six different radionuclides ((188)Re, (186)Re, (32)P, (90)Y, (67)Cu, (131)I) were calculated. Dose-rate profiles were calculated for two source geometries: (1) a large bath of radioactivity in which the tumor is submerged, and (2) surface-bound radioactivity that results from tumor targeting. RESULTS: The bath geometry produced profiles that were uniform for sufficiently small tumors. For high-energy emitters (i.e., (90)Y and (188)Re), uniformity was maintained up to a tumor radius of 100 microm. For lower energy emitters (i.e., (67)Cu and (131)I) deviations from uniformity start to appear at a tumor radius of 50 microm. Surface-bound radioactivity produced a much greater range of dose-rates within tumors of all sizes. Lower energy emitters bound to the surface of tumors produce higher dose-rates for very small micrometastases compared with high-energy emitters. Upon consideration of the simultaneous contributions from both source geometries, we believe that liposome-mediated radioimmunotherapy would benefit from the inclusion of a high-energy beta emitter, possibly as a component of a cocktail of radionuclides. CONCLUSIONS: The calculated dose-rate profiles provide a tool for making tumor control probability estimations for micrometastases and for assessing the potential benefit offered by a targeted approach over a nontargeted approach. These calculations also suggest that the inclusion of a high-energy beta emitter is appropriate for this treatment modality.

Beta Particles↗