Spiridon V. Spirou

A gradient inverse planning algorithm with dose-volume constraints.

An inverse planning algorithm for determining the intensity-modulated beams that will most closely generate a desired dose distribution is presented. The algorithm is three-dimensional and does not explicitly depend on beam energies and modalities. It allows a single prescription dose or a window of acceptable doses to be specified for the target, with additional constraints to account for under- or over-dosing. For the protection of organs at risk, it provides maximum-dose and dose-volume constraints. The latter apply to the entire volume of the organ exposed to the corresponding dose levels. Several levels of each type of constraint, with varying penalty weights, may be specified for each organ. The objective function that serves as the measure of the goodness of the solution is of the least-squares type and is minimized using conjugate gradient methods. Typical clinical cases involving 40,000 points and 4000 rays to be determined require about 10 min of CPU time on a DEC AlphaStation. Results are presented for two clinical sites, prostate and lung. The optimization algorithm yielded plans that featured higher target dose homogeneity, compared with the human planners plan, while selectively sparing more of the normal organs at the desired dose regions.

Treatment planning and delivery of intensity-modulated radiation therapy for primary nasopharynx cancer

PURPOSE To implement intensity-modulated radiation therapy (IMRT) for primary nasopharynx cancer and to compare this technique with conventional treatment methods. METHODS AND MATERIALS Between May 1998 and June 2000, 23 patients with primary nasopharynx cancer were treated with IMRT delivered with dynamic multileaf collimation. Treatments were designed using an inverse planning algorithm, which accepts dose and dose-volume constraints for targets and normal structures. The IMRT plan was compared with a traditional plan consisting of phased lateral fields and a three-dimensional (3D) plan consisting of a combination of lateral fields and a 3D conformal plan. RESULTS Mean planning target volume (PTV) dose increased from 67.9 Gy with the traditional plan, to 74.6 Gy and 77.3 Gy with the 3D and IMRT plans, respectively. PTV coverage improved in the parapharyngeal region, the skull base, and the medial aspects of the nodal volumes using IMRT and doses to all normal structures decreased compared to the other treatment approaches. Average maximum cord dose decreased from 49 Gy with the traditional plan, to 44 Gy with the 3D plan and 34.5 Gy with IMRT. With the IMRT plan, the volume of mandible and temporal lobes receiving more than 60 Gy decreased by 10-15% compared to the traditional and 3D plans. The mean parotid gland dose decreased with IMRT, although it was not low enough to preserve salivary function. CONCLUSION Lower normal tissue doses and improved target coverage, primarily in the retropharynx, skull base, and nodal regions, were achieved using IMRT. IMRT could potentially improve locoregional control and toxicity at current dose levels or facilitate dose escalation to further enhance locoregional control.

Intensity-modulated tangential beam irradiation of the intact breast

PURPOSE To evaluate the potential benefits of intensity modulated tangential beams in the irradiation of the intact breast. METHODS AND MATERIALS Three-dimensional treatment planning was performed on five left and five right breasts using standard wedged and intensity modulated (IM) tangential beams. Optimal beam parameters were chosen using beams-eye-view display. For the standard plans, the optimal wedge angles were chosen based on dose distributions in the central plane calculated without inhomogeneity corrections, according to our standard protocol. Intensity-modulated plans were generated using an inverse planning algorithm and a standard set of target and critical structure optimization criteria. Plans were compared using multiple dose distributions and dose volume histograms for the planning target volume (PTV), ipsilateral lung, coronary arteries, and contralateral breast. RESULTS Significant improvements in the doses to critical structures were achieved using intensity modulation. Compared with a standard-wedged plan prescribed to 46 Gy, the dose from the IM plan encompassing 20% of the coronary artery region decreased by 25% (from 36 to 27 Gy) for patients treated to the left breast; the mean dose to the contralateral breast decreased by 42% (from 1.2 to 0.7 Gy); the ipsilateral lung volume receiving more than 46 Gy decreased by 30% (from 10% to 7%); the volume of surrounding soft tissue receiving more than 46 Gy decreased by 31% (from 48% to 33%). Dose homogeneity within the target volume improved greatest in the superior and inferior regions of the breast (approximately 8%), although some decrease in the medial and lateral high-dose regions (approximately 4%) was also observed. CONCLUSION Intensity modulation with a standard tangential beam arrangement significantly reduces the dose to the coronary arteries, ipsilateral lung, contralateral breast, and surrounding soft tissues. Improvements in dose homogeneity throughout the target volume can also be achieved, particularly in the superior and inferior regions of the breast. It remains to be seen whether the dosimetric improvements achievable with IMRT will lead to significant clinical outcome improvements.

Intensity-modulated radiotherapy

Intensity-modulated radiotherapy represents a recent advancement in conformal radiotherapy. It employs specialized computer-driven technology to generate dose distributions that conform to tumor targets with extremely high precision. Treatment planning is based on inverse planning algorithms and iterative computer-driven optimization to generate treatment fields with varying intensities across the beam section. Combinations of intensity-modulated fields produce custom-tailored conformal dose distributions around the tumor, with steep dose gradients at the transition to adjacent normal tissues. Thus far, data have demonstrated improved precision of tumor targeting in carcinomas of the prostate, head and neck, thyroid, breast, and lung, as well as in gynecologic, brain, and paraspinal tumors and soft tissue sarcomas. In prostate cancer, intensity-modulated radiotherapy has resulted in reduced rectal toxicity and has permitted tumor dose escalation to previously unattainable levels. This experience indicates that intensity-modulated radiotherapy represents a significant advancement in the ability to deliver the high radiation doses that appear to be required to improve the local cure of several types of tumors. The integration of new methods of biologically based imaging into treatment planning is being explored to identify tumor foci with phenotypic expressions of radiation resistance, which would likely require high-dose treatments. Intensity-modulated radiotherapy provides an approach for differential dose painting to selectively increase the dose to specific tumor-bearing regions. The implementation of biologic evaluation of tumor sensitivity, in addition to methods that improve target delineation and dose delivery, represents a new dimension in intensity-modulated radiotherapy research.

Testing of dynamic multileaf collimation

It has been shown that intensity-modulated fields have the potential to deliver optimum dose distributions, i.e., high dose uniformity in the target and lower doses in the surrounding critical organs. One way to deliver such fields is by using dynamic multileaf collimation (DMLC). This capability is already available in research mode on some treatment machines. While much effort has been devoted to developing algorithms for DMLC, the mechanical reliability of this new treatment delivery mode has not been fully studied. In this work, we report a series of tests designed to investigate the mechanical aspects of DMLC and their implications on dosimetry. Specifically, these tests were designed to examine (1) the stability of leaf speed, (2) the effect of lateral disequilibrium on dose profiles between adjacent leaves, (3) the significance of acceleration and deceleration of leaf motion, (4) the effect of positional accuracy and rounded-end of the leaves, and (5) create a simple test pattern that may serve as a basis for routine quality assurance checks. Results of these tests are presented. The implications on dosimetry and consideration for the design of leaf motion are discussed.

Smoothing intensity-modulated beam profiles to improve the efficiency of delivery.

Intensity-modulated beam profiles are generated by an inverse planning or optimization algorithm, a process that, being computationally complex and intensive, is inherently susceptible to noise and numerical artifacts. These artifacts make delivery of the beams more difficult, oftentimes for little, if any, observable improvement in the dose distributions. In this work we examine two approaches for smoothing the beam profiles. The first approach is to smooth the beam profiles subsequent to each iteration in the optimization process (method A). The second approach is to include a term within the objective function that specifies the smoothness of the profiles as an optimization criterion (method B). The two methods were applied to a phantom study as well as three clinical sites: paraspinal, nasopharynx, and prostate. For the paraspinal and nasopharynx cases, which have critical organs with low tolerance doses in close proximity, method B produced sharper dose gradients, better target dose homogeneity, and more critical organ sparing. In the less demanding prostate case, the two methods give similar results. In addition, method B is more efficient during optimization, requiring fewer iterations, but less efficient during DMLC delivery, requiring a longer beam-on time.

Inverse planning algorithms for external beam radiation therapy.

Intensity-modulated radiation therapy (IMRT) is a new treatment technique that has the potential to produce superior dose distributions to those of conventional techniques. An important step in IMRT is inverse planning, or optimization. This is a process by which the optimum intensity distribution is determined by minimizing (or maximizing) an objective function. For radiation therapy, the objective function is used to describe the clinical goals, which can be expressed in terms of dose and dose/volume requirements, or in terms of biological indices. There are 2 types of search algorithms, stochastic and deterministic. Typical algorithms that are currently in use are presented. For clinical implementations, other issues are also discussed, such as global minimum vs. local minima, dose uniformity in the target and sparing of normal tissues, smoothing of the intensity profile, and skin flash. To illustrate the advantages of IMRT, clinical examples for the treatment of the prostate, nasopharynx, and breast are presented. IMRT is an emerging technique that has shown encouraging results thus far. However, the technique is still in its infancy and more research and improvements are needed. For example, the effects of treatment uncertainties on the planning and delivery of IMRT requires further study. As with any new technology, IMRT should be used with great caution.

Optimization of conformal thoracic radiotherapy using cone-beam CT imaging for treatment verification.

PURPOSE Megavoltage cone-beam computed tomography (MVCBCT) has been proposed for treatment verification in conformal radiotherapy. However, the doses required for such imaging may compromise the quality of the delivered dose distribution. The present paper explores the effect of cone-beam imaging on dose homogeneity and critical organ dose and the use of our new tool, adapted intensity-modulated radiation therapy (AIMRT). METHODS AND MATERIALS Three types of treatment plans were devised (3D-CRT [three-dimensional conformal radiotherapy], IMRT [intensity-modulated radiotherapy], and AIMRT) based on 4 patients with thoracic malignancies. MVCBCT fields were then integrated into the plans. The MVCBCT technique used 21 imaging portals at 10 degrees intervals. The MVCBCT apertures were shaped to conform to the planning target volume with a 6-mm margin. In a second set of plans, the field size was expanded by a further 2 cm. The unoptimized MVCBCT dose distribution was incorporated into the IMRT plan using AIMRT. RESULTS Normal-tissue complication probability with MVCBCT is acceptable for all plans at the 66.6 Gy level, but exceeds tolerance for both 3D-CRT alone and 3D-CRT with MVCBCT at higher doses. In contrast, the use of AIMRT planning with MVCBCT allowed safe dose escalation to 85 Gy. Expanding the MVCBCT aperture provided better anatomic visibility with an acceptable lung dose. The results using IMRT with MVCBCT fell between the values measured for 3D-CRT and AIMRT with MVCBCT. CONCLUSION The present study is the first to demonstrate that MVCBCT can be incorporated into 3D-CRT and IMRT planning with minimal effect on planning target volume homogeneity and dose to critical structures. This paves the way for highly conformal radiotherapy at greater doses delivered with increased confidence and safety.

A new method of incorporating systematic uncertainties in intensity-modulated radiotherapy optimization.

Uncertainties in tumor position during intensity-modulated radiotherapy (IMRT) plan optimization are usually accounted for by adding margins to a clinical target volume (CTV), or additionally, to organs at risk (OAR). The former approach usually favors target coverage over OAR protection, whereas the latter does not account for correlation in target and OAR movement. We investigate a new approach to incorporate systematic errors in tumor and organ position. The method models a distribution of systematic errors due to setup error and organ motion with displaced replicas of volumes of interest, each representing the patient geometry for a possible systematic error, and maximizes a score function that counts the number of replicas meeting dose or biological constraints for both CTV and OAR. Dose constraints are implemented by logistic functions of Niemierkos generalized model of equivalent uniform dose (EUD). The method is applied to prostate and nasopharynx IMRT plans, in which CTV and OAR each consists of five replicas, one representing no error (the position in the planning CT) and the other four discrete systematic setup displacements in one dimension with equal probability. The resulting IMRT plans are compared with those from two other EUD-based optimizations: a standard planning target volume (PTV) approach consisting of a single replica of each OAR in the planned position and a single PTV encompassing all CTV replicas, and a PTV-PRV approach consisting of a single PTV and a single planning risk volume (PRV) for each OAR encompassing all replicas. When systematic error is present, multiple-replica optimization provides better critical organ protection while maintaining similar target coverage compared with the PTV approach, and provides better CTV-to-OAR therapeutic ratio compared with the PTV-PRV instances where there is substantial PTV-PRV overlap. The method can be used for other systematic errors due to organ motion and deformation.