Rotation effects on the target-volume margin determination.

Rotational setup errors are usually neglected in most clinical centers. An analytical formula is developed to determine the extra margin between clinical target volume (CTV) and planning target volume (PTV) to account for setup errors. The proposed formula corrects for both translational and rotational setup errors and then incorporated into margin determination for PTV.

Using a novel dose QA tool to quantify the impact of systematic errors otherwise undetected by conventional QA methods: clinical head and neck case studies.

Recent studies have demonstrated that per-beam planar intensity-modulated radiation therapy (IMRT) quality assurance (QA) passing rates may not predict clinically relevant patient dose errors. This work is to evaluate the effect of dose variations introduced in dynamic multi-leaf collimator (DMLC) modeling and delivery processes on clinically relevant metrics for IMRT. Ten head and neck (HN) IMRT plans were randomly selected for this study. The conventional per-beam IMRT QA was performed for each plan by 2 different methods: (1) with gantry angle of 0 (gantry pointing downward) for all IMRT fields and (2) with gantry at specific angles as designed in the IMRT plan. For each patient, a batch analysis was done for each scenario and then imported to the 3DVH (Sun Nuclear Corp.) for processing. A "corrected DVH" was generated and compared to the DVH from the treatment plan. Their differences represented errors introduced from the combination of the treatment planning system (TPS) dose calculation algorithm and beam-delivery. The dose metrics from the two scenarios were compared with the corresponding calculated doses, and then their differences were analyzed. Although all per-beam planar IMRT QA had high Gamma passing rates 99.3 ± 1.3% (92.3-100%) for "2%/3 mm" criteria, there were significant errors in some of the calculated clinical dose metrics. Such as, for all the plans studied, there were as much as 3.2%, 5.7%, 5.6%, 2.3%, 4.1%, and 23.8% errors found in max cord dose, max brainstem dose, mean parotid dose, larynx dose, oral cavity dose, and PTV(D95) dose, respectively. The differences in errors for clinical metrics obtained between the two scenarios (zero gantry angle vs. true gantry angles) can also be significant: max cord dose (2.9% vs. 0.2%), max brainstem dose (3.8% vs. 0.4%), mean parotid dose (2.3% vs. 4.5%), mean larynx dose (3.9% vs. 2.0%), mean oral cavity dose (1.6% vs. 3.9%), and PTV(D95) dose (-0.4% vs. -2.6%). However, in the two scenarios, a strong and clear correlation between the dose differences for each of the organ structures was observed. This study confirms that conventional IMRT QA performance metrics are not predictive of dose errors in PTV and organs-at-risk. The clinically-relevant-dose QA has allowed us to predict the patient dose-volume relationships.

Three independent one-dimensional margins for single-fraction frameless stereotactic radiosurgery brain cases using CBCT.

PURPOSE: Setting a proper margin is crucial for not only delivering the required radiation dose to a target volume, but also reducing the unnecessary radiation to the adjacent organs at risk. This study investigated the independent one-dimensional symmetric and asymmetric margins between the clinical target volume (CTV) and the planning target volume (PTV) for linac-based single-fraction frameless stereotactic radiosurgery (SRS). METHODS: The authors assumed a Dirac delta function for the systematic error of a specific machine and a Gaussian function for the residual setup errors. Margin formulas were then derived in details to arrive at a suitable CTV-to-PTV margin for single-fraction frameless SRS. Such a margin ensured that the CTV would receive the prescribed dose in 95% of the patients. To validate our margin formalism, the authors retrospectively analyzed nine patients who were previously treated with noncoplanar conformal beams. Cone-beam computed tomography (CBCT) was used in the patient setup. The isocenter shifts between the CBCT and linac were measured for a Varian Trilogy linear accelerator for three months. For each plan, the authors shifted the isocenter of the plan in each direction by ±3 mm simultaneously to simulate the worst setup scenario. Subsequently, the asymptotic behavior of the CTV V80% for each patient was studied as the setup error approached the CTV-PTV margin. RESULTS: The authors found that the proper margin for single-fraction frameless SRS cases with brain cancer was about 3 mm for the machine investigated in this study. The isocenter shifts between the CBCT and the linac remained almost constant over a period of three months for this specific machine. This confirmed our assumption that the machine systematic error distribution could be approximated as a delta function. This definition is especially relevant to a single-fraction treatment. The prescribed dose coverage for all the patients investigated was 96.1% ± 5.5% with an extreme 3-mm setup error in all three directions simultaneously. It was found that the effect of the setup error on dose coverage was tumor location dependent. It mostly affected the tumors located in the posterior part of the brain, resulting in a minimum coverage of approximately 72%. This was entirely due to the unique geometry of the posterior head. CONCLUSIONS: Margin expansion formulas were derived for single-fraction frameless SRS such that the CTV would receive the prescribed dose in 95% of the patients treated for brain cancer. The margins defined in this study are machine-specific and account for nonzero mean systematic error. The margin for single-fraction SRS for a group of machines was also derived in this paper.

Feasibility study of real-time planning for stereotactic radiosurgery.

PURPOSE: 3D rotational setup errors in radiotherapy are often ignored by most clinics due to inability to correct or simulate them accurately and efficiently. There are two types of rotation-related problems in a clinical setting. One is to assess the affected dose distribution in real-time if correction is not applied and the other one is to correct the rotational setup errors prior to the initiation of the treatment. Here, the authors present the analytical solutions to both problems. METHODS: (1) To assess the real-time dose distribution, eight stereotactic radiosurgery (SRS) cases were used as examples. For each plan, two new sets of beams with different table, gantry, and collimator angles were given in analytical forms as a function of patient rotational errors. The new beams simulate the rotational effects of the patient during the treatment setup. By using one arbitrary set of beams, SRS plans were recomputed with a series of different combinations of patient rotational errors, ranging from (-5°, -5°, -5°) to (5°, 5°, 5°) (roll, pitch, and yaw) with an increment of 1° and compared with those without rotational errors. For each set of rotational errors, its corresponding equivalent beams were computed using the analytical solutions and then used for dose calculation. (2) To correct for the rotational errors, two new sets of table, gantry, and collimator angles were derived analytically to validate the previously published derivation. However, in the derivation, a novel methodology was developed and two sets of table, gantry, and collimator angles were obtained in analytical forms. The solutions provide an alternative approach to rotational error correction by rotating the couch, gantry, and collimator rather than the patient. RESULTS: For demonstration purpose, the above-derived new beams were implemented in a treatment planning system (TPS) to study the rotational effects on the SRS cases. For each case, the authors have generated ten additional plans that accounted for different rotations of the patient. They have found that rotations have an insignificant effect on the minimal, maximum, mean doses, and V80% of the planning target volume (PTV) when the rotations were relatively small. This was particularly true for the small and near-spherical targets. They, however, did change V95% significantly when the rotations approached 5°. The theory has been validated with clinical SRS cases and proven to be practical and viable. The preliminary results demonstrate that the rotational effects are patient-specific and depend on several important factors, such as the PTV size, the PTV location, and the beam configuration. The solutions given in this paper are of great potential values in clinical applications. CONCLUSIONS: They have derived the analytical solutions to a new set of table, gantry, and collimator angles for a given treatment beam configuration as a function of patient rotational errors. One solution was used to assess the dosimetric effects of an imperfect patient setup and the other one was used to correct for the setup errors without rotating the patient. Compared to the widely adopted method of rotation effect assessment by importing the rotational CT images into TPS, the equivalent beam approach is simple and accurate. The analytical solutions to correcting for rotational setup errors prior to treatment were also derived. Based on the initial clinical investigations, they firmly believe that clinically viable real-time treatment planning and adaptive radiation therapy are feasible with this novel method.

Confirmation of skin doses resulting from bolus effect of intervening alpha-cradle and carbon fiber couch in radiotherapy.

In this study, we verified the treatment planning calculations of skin doses with the incorporation of the bolus effect due to the intervening alpha-cradle (AC) and carbon fiber couch (CFC) using radiochromic EBT2 films. A polystyrene phantom (25 × 25 × 15 cm(3)) with six EBT2 films separated by polystyrene slabs, at depths of 0, 0.1, 0.2, 0.5, 1, 1.4 cm, was positioned above an AC, which was ~1 cm thick. The phantom and AC assembly were CT scanned and the CT-images were transferred to the treatment planning system (TPS) for calculations in three scenarios: (A) ignoring AC and CFC, (B) accounting for AC only, (C) accounting for both AC and CFC. A single posterior 10 × 10 cm(2) field, a pair of posterior-oblique 10 × 10 cm(2) fields, and a posterior IMRT field (6 MV photons from a Varian Trilogy linac) were planned. For each radiation field configuration, the same MU were used in all three scenarios in the TPS. Each plan for scenario C was delivered to expose a stack of EBT2 films in the phantom through AC and CFC. In addition, in vivo EBT2 film measurement on a lung cancer patient immobilized with AC undergoing IMRT was also included in this study. Point doses and planar distributions generated from the TPS for the three scenarios were compared with the data from the EBT2 film measurements. For all the field arrangements, the EBT2 film data including the in vivo measurement agreed with the doses calculated for scenario (C), within the uncertainty of the EBT2 measurements (~4%). For the single posterior field (a pair of posterior-oblique fields), the TPS generated doses were lower than the EBT2 doses by 34%, 33%, 31%, 13% (34%, 31%, 31%, 11%) for scenario A and by 27%, 25%, 22%, 8% (25%, 21%, 21%, 6%) for scenario B at the depths of 0, 0.1, 0.2, 0.5 cm, respectively. For the IMRT field, the 2D dose distributions at each depth calculated in scenario C agree with those measured data. When comparing the central axis doses for the IMRT field, we found the TPS generated doses for scenario A (B) were lower than the EBT2 data by 35%, 34%, 31%, 16% (29%, 26%, 23%, 10%) at the depths of 0, 0.1, 0.2, 0.5 cm, respectively. There were no significant differences for the depths of 1.0 and 1.4 cm for all the radiation fields studied. TPS calculation of doses in the skin layers accounting for AC and CFC was verified by EBT2 film data. Ignoring the presence of AC and/or CFC in TPS calculation would significantly underestimate the doses in the skin layers. For the clinicians, as more hypofractionated regimens and stereotactic regimens are being used, this information will be useful to avoid potential serious skin toxicities, and also assist in clinical decisions and report these doses accurately to relevant clinical trials/cooperative groups, such as RTOG.

Estimating dose to implantable cardioverter-defibrillator outside the treatment fields using a skin QED diode, optically stimulated luminescent dosimeters, and LiF thermoluminescent dosimeters.

The purpose of this work was to determine the relative sensitivity of skin QED diodes, optically stimulated luminescent dosimeters (OSLDs) (microStar™ DOT, Landauer), and LiF thermoluminescent dosimeters (TLDs) as a function of distance from a photon beam field edge when applied to measure dose at out-of-field points. These detectors have been used to estimate radiation dose to patients' implantable cardioverter-defibrillators (ICDs) located outside the treatment field. The ICDs have a thin outer case made of 0.4- to 0.6-mm-thick titanium (∼2.4-mm tissue equivalent). A 5-mm bolus, being the equivalent depth of the devices under the patient's skin, was placed over the ICDs. Response per unit absorbed dose-to-water was measured for each of the dosimeters with and without bolus on the beam central axis (CAX) and at a distance up to 20 cm from the CAX. Doses were measured with an ionization chamber at various depths for 6- and 15-MV x-rays on a Varian Clinac-iX linear accelerator. Relative sensitivity of the detectors was determined as the ratio of the sensitivity at each off-axis distance to that at the CAX. The detector sensitivity as a function of the distance from the field edge changed by ± 3% (1-11%) for LiF TLD-700, decreased by 10% (5-21%) for OSLD, and increased by 16% (11-19%) for the skin QED diode (Sun Nuclear Corp.) at the equivalent depth of 5 mm for 6- or 15-MV photon energies. Our results showed that the use of bolus with proper thickness (i.e., ∼d(max) of the photon energy) on the top of the ICD would reduce the scattered dose to a lower level. Dosimeters should be calibrated out-of-field and preferably with bolus equal in thickness to the depth of interest. This can be readily performed in clinic.

The development of a novel radiation treatment modality - volumetric modulated arc therapy.

Recent theoretical studies and clinical investigations have indicated that volumetric modulated arc therapy (VMAT) can produce equal or better treatment plans than intensity modulated radiation therapy (IMRT), while achieving a significant reduction in treatment time. Built upon the concept of aperture-based multi-level beam source sampling optimization, VMAT has overcome many engineering constraints and become a clinically viable radiation treatment modality. At this point in time, however, there are only two commercial VMAT treatment planning systems (TPS) on the market, which severely limit the dissemination of this novel technology. To address this issue, we recently have successfully developed our own version of VMAT TPS. In this paper, we present our preliminary test results.

Comparison of two treatment approaches for prostate cancer: intensity-modulated radiation therapy combined with 125I seed-implant brachytherapy or 125I seed-implant brachytherapy alone.

The purpose of the present study was to assess the results of two different treatment approaches for clinically localized prostate cancer: intensity-modulated radiation therapy (IMRT) followed by 125I seed-implant brachytherapy and 125I seed-implant brachytherapy alone. We studied our 30 most recent consecutive patients. The sample population consisted of 15 cases treated with IMRT (50.4 Gy) followed by 125I seed-implant boost (95 Gy), and 15 cases treated with 125I seed implant only (144 Gy). We analyzed established dosimetric indices and various clinical parameters. In addition, we also evaluated and compared the acute urinary morbidities of the two treatment approaches, as assessed by the international prostate symptom score (IPSS). In our series, acute urinary morbidity was slightly increased with IMRT followed by 125I seed-implant brachytherapy as compared with 125I seed-implant brachytherapy alone. In addition, we observed no statistically significant correlation between the IPSS and the maximum or mean urethral dose. The combination of IMRT and seed-implant brachytherapy presents an alternative opportunity to treat clinically localized prostate cancer. The full potential of the procedure needs to be further investigated.

From intensity modulated radiation therapy to 4D radiation therapy--an advance in targeting mobile lung tumors.

Intensity modulated radiation therapy (IMRT) has been widely used in the treatment of lung cancer. The highly conformal dose distribution with steep gradients could miss the target if respiratory motion is not carefully considered during the treatment planning. The issue becomes particularly critical when dose escalation technique is used. To account for this periodical respiratory motion, the common practice is to add an empirical population-based safety margin to the clinical target volume (CTV). However, such a uniform margin does not reflect the fact that respiratory motion is not isotropic. In addition, it is not tailored to each individual patient. Thus, it is not optimal in both tumor targeting and normal tissue sparing. Here, we present our approach to 4D radiation therapy using the Bellows tracking system for targeting mobile lung tumors. The objective was to develop a clinically viable procedure for routine 4D treatment planning.

A model-aided segmentation in urethra identification based on an atlas human autopsy image for intensity modulated radiation therapy.

In order to protect urethra in radiation therapy of prostate cancer, the urethra must be identified and localized as an organ at risk (OAR) for the inverse treatment planning in intensity modulated radiation therapy (IMRT). Because the prostatic urethra and its surrounding prostate tissue have similar physical characteristics, such as linear attenuation coefficient and density, it is difficult to distinct the OAR from the target in CT images. To localize the urethra without using contrast agent or additional imaging modalities other than planning CT images, a different approach was developed using a standard atlas of human anatomy image. This paper reports an investigation, in which an adult urethra was modeled based on a human anatomic image. An elastic model was build to account for a uniform tissue deformation of the prostate. This model was then applied to patients to localize their urethras and preliminary results are presented.

A novel radiation therapy technique for malignant pleural mesothelioma combining electrons with intensity-modulated photons.

BACKGROUND AND PURPOSE: To investigate the feasibility and potential benefits of combining electron and photon intensity modulated radiotherapy (IMRT) for patients with malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: The planning CT images of 11 MPM patients, six after extrapleural pneumonectomy (EPP) and five after pleurectomy/decortication (P/D), were used for this study. These cases were planned with photon IMRT alone and photon IMRT combined with electrons (IMRT+e). The latter approach incorporated the electron dose into the inverse planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. RESULTS: For all patients, the PTV was well covered and doses to critical structures were clinically acceptable for all patients with both techniques. However, IMRT+e exhibited a distinct advantage in reducing the doses to the liver, ipsilateral kidney, contralateral kidney, and heart (P=0.002, 0.003, 0.025, and 0.001, respectively). CONCLUSIONS: This study showed that IMRT or IMRT+e is a viable treatment modality for MPM patients. Both plans can provide excellent target coverage and normal tissue sparing, but with the addition of electron beams, the critical structures can be further spared. Additional refining of the electron contribution is expected to further reduce radiation-induced morbidity.

The treatment of extensive scalp lesions combining electrons with intensity-modulated photons.

This study was to investigate the feasibility and potential benefits of combining electrons with intensity modulated photons (IMRT+e) for patients with extensive scalp lesions. A case of a patient with an extensive scalp lesion, in which the target volume covered the entire front half of the scalp, is presented. This approach incorporated the electron dose into the inverse treatment planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Thermoluminescent dosimeters (TLD), diodes, and GAFCHROMIC EBT films were used to verify the accuracy of the techniques. The IMRT+e plan produced a superior dose distribution to the patient as compared to the IMRT plan in terms of reduction of the dose to the brain with the same dose conformity and homogeneity in the target volumes. This study showed that IMRT+e is a viable treatment modality for extensive scalp lesions patients. It provides a feasible alternative to existing treatment techniques, resulting in improved homogeneity of dose to the PTV compared to conventional electron techniques and a decrease in dose to the brain compared to photon IMRT alone.

Inter-modality variation in gross tumor volume delineation in 18FDG-PET guided IMRT treatment planning for lung cancer.

Rapid advances in 18FDG-PET/CT technology and novel co-registration algorithms have created a strong interest in 18FDG-PET/CT's application in intensity modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT). Accurate target volume delineation, particularly identification of pathologically positive lymph nodes, could translate into favorable treatment outcome. However, gross tumor volume (GTV) delineation on both CT and 18FDG-PET is very sensitive to observer variation. The objectives of the study were to investigate the inter-modality variation in gross tumor volume delineation defined by two imaging modalities for lung cancer: CT and 18FDG-PET/CT and its dosimetric implications in intensity modulated radiation therapy (IMRT).

Results of a one year survey of output for linear accelerators using IMRT and non-IMRT techniques.

This paper presents the results of a one year survey of treated fields for 3 treatment machines at our New Jersey regional center. One machine predominantly treated IMRT prostate patients using a sliding window technique. The others were not equipped to deliver IMRT. Information obtained for each treated field included patient number, modality, monitor units delivered, gantry angle, and time. Data was obtained directly from our record and verify system and analyzed using a spreadsheet. We studied workload (MU/week), patient load, and average MU per patient as a function of time, as well as angular distributions and number of treatment fractions per patient. We also calculated the fraction of time the beam was on during treatments. By the end of the survey year, the workload of the IMRT machine reached approximately 100,000 MU/week and that of the non-IMRT machines was approximately 40-45000 MU/week. This was due predominantly to the higher number of monitor units for IMRT plans. Patient loads were not significantly different for the 3 machines. Duty cycle was 14% and 16% for the non-IMRT machines and 27% for the IMRT machine. The difference in workload for IMRT treatments relative to non-IMRT treatments confirms an earlier study performed at our institution using a much smaller data sample. One needs to consider the increase in leakage associated with this higher workload when designing shielding for an IMRT room.

Comparison of intensity-modulated radiotherapy with three-dimensional conformal radiation therapy planning for glioblastoma multiforme.

This study was designed to assess the feasibility and potential benefit of using intensity-modulated radiotherapy (IMRT) planning for patients newly diagnosed with glioblastoma multiforme (GBM). Five consecutive patients with confirmed histopathologically GBM were entered into the study. These patients were planned and treated with 3-dimensional conformal radiation therapy (3DCRT) using our standard plan of 3 noncoplanar wedged fields. They were then replanned with the IMRT method that included a simultaneous boost to the gross tumor volume (GTV). The dose distributions and dose-volume histograms (DHVs) for the planning treatment volume (PTV), GTV, and the relevant critical structures, as obtained with 3DCRT and IMRT, respectively, were compared. In both the 3DCRT and IMRT plans, 59.4 Gy was delivered to the GTV plus a margin of 2.5 cm, with doses to critical structures below the tolerance threshold. However, with the simultaneous boost in IMRT, a higher tumor dose of approximately 70 Gy could be delivered to the GTV, while still maintaining the uninvolved brain at dose levels of the 3DCRT technique. In addition, our experience indicated that IMRT planning is less labor intensive and time consuming than 3DCRT planning. Our study shows that IMRT planning is feasible and efficient for radiotherapy of GBM. In particular, IMRT can deliver a simultaneous boost to the GTV while better sparing the normal brain and other critical structures.

Technological advances in external-beam radiation therapy for the treatment of localized prostate cancer.

The relative inability of conventional radiotherapy to control localized prostate cancer results from resistance of subpopulations of tumor clonogens to dose levels of 65 to 70 Gy, the maximum feasible with traditional two-dimensional (2D) treatment planning and delivery techniques. Several technological advances have enhanced the precision and improved the outcome of external-beam radiotherapy. The three-dimensional conformal radiotherapy (3D-CRT) approach has permitted significant increases in the tumor dose to levels beyond those feasible with conventional techniques. Intensity-modulated radiotherapy (IMRT), an advanced form of conformal radiotherapy, has resulted in reduced rectal toxicity, permitting tumor dose escalation to previously unattainable levels with a concomitant improvement in local tumor control and disease-free survival. The combination of androgen deprivation and conventional-dose radiotherapy, tested mainly in patients with locally advanced disease, has also produced significant outcome improvements. Whether androgen deprivation will preclude the need for dose escalation or whether high-dose radiotherapy will obviate the need for androgen deprivation remains unknown. In some patients, both approaches may be necessary to maximize the probability of cure. In view of the favorable benefit-risk ratio of high-dose IMRT, the design of clinical trials to resolve these critical questions is essential.

A study of the effects of internal organ motion on dose escalation in conformal prostate treatments.

BACKGROUND AND PURPOSE: To assess the effect of internal organ motion on the dose distributions and biological indices for the target and non-target organs for three different conformal prostate treatment techniques. MATERIALS AND METHODS: We examined three types of treatment plans in 20 patients: (1) a six field plan, with a prescribed dose of 75.6 Gy; (2) the same six field plan to 72 Gy followed by a boost to 81 Gy; and (3) a five field plan with intensity modulated beams delivering 81 Gy. Treatment plans were designed using an initial CT data set (planning) and applied to three subsequent CT scans (treatment). The treatment CT contours were used to represent patient specific organ displacement; in addition, the dose distribution was convolved with a Gaussian distribution to model random setup error. Dose-volume histograms were calculated using an organ deformation model in which the movement between scans of individual points interior to the organs was tracked and the dose accumulated. The tumor control probability (TCP) for the prostate and proximal half of seminal vesicles (clinical target volume, CTV), normal tissue complication probability (NTCP) for the rectum and the percent volume of bladder wall receiving at least 75 Gy were calculated. RESULTS: The patient averaged increase in the planned TCP between plan types 2 and 1 and types 3 and 1 was 9.8% (range 4.9-12.5%) for both, whereas the corresponding increases in treatment TCP were 9.0% (1.3-16%) and 8.1% (-1.3-13.8%). In all patients, plans 2 and 3 (81 Gy) exhibited equal or higher treatment TCP than plan 1 (75.6 Gy). The maximum treatment NTCP for rectum never exceeded the planning constraint and percent volume of bladder wall receiving at least 75 Gy was similar in the planning and treatment scans for all three plans. CONCLUSION: For plans that deliver a uniform prescribed dose to the planning target volume (PTV) (plan 1), current margins are adequate. In plans that further escalate the dose to part of the PTV (plans 2 and 3), in a fraction of the cases the CTV dose increase is less than planned, yet in all cases the TCP values are higher relative to the uniform dose PTV (plan 1). Doses to critical organs remain within the planning criteria.

Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy.

PURPOSE: To analyze acute lung toxicity data of non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy in terms of dosimetric variables, location of dose within subvolumes of the lungs, and models of normal-tissue complication probability (NTCP). METHODS AND MATERIALS: Dose distributions of 49 non-small-cell lung cancer patients treated in a dose escalation protocol between 1992 and 1999 were analyzed (dose range: 57.6-81 Gy). Nine patients had RTOG Grade 3 or higher acute lung toxicity. Correlation with dosimetric and physical variables, as well as Lyman and parallel NTCP models, was assessed. Lungs were evaluated as a single structure, as superior and inferior halves (to assess significance of dose to upper and lower lungs), and as ipsilateral and contralateral lungs. RESULTS: For the whole lung, Grade 3 or higher pneumonitis was significantly correlated (p 0.5 for superior lung indices, and >0.1 for contralateral lung indices studied). CONCLUSIONS: For these patients, commonly used dosimetric and NTCP models are significantly correlated with >or= Grade 3 pneumonitis. Equivalently strong correlations are found in the lower portion of the lungs and the ipsilateral lung, but not in the upper portion or contralateral lung.

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.

Fitting of tissue tolerance data to analytic function: improving the therapeutic ratio.

Response of human tissues to ionizing radiation is a complex process. It is influenced by many factors, such as use of chemotherapy drugs and underlying diseases such as diabetes and/or lung emphysema. A phenomenological model such as Lyman's is an attempt to predict the complication, for a variety of tissues, in the absence of these factors. The use of the model requires the knowledge of the parameters to predict the response for a specific endpoint. Clinical response data are needed to determine these parameters. Emami et al. [6] have provided some data, based on pre-CT and pre-3-D information, for some of the most serious complications. Based on this information the parameters were determined [4]. However, to validate and further improve the predictive power of the model, improved clinical response data are needed. With CT-based 3-D treatment planning systems the dose-volume information is routinely produced. Efforts by the radiation oncology community are needed to collect this information and correlate it with the clinical outcomes in a uniform and systematic way, not only for the most serious complications but also for less severe radiation-induced complications that are routinely considered in radiation therapy. Also, the information about the tissue response with underlying disease and drugs will be useful. The use of NTCP for plan comparison is useful. However, the incorporation of TCP and NTCP for designing the plan is remarkable. A plan can be optimized for the best outcome for the patient. It is hoped that as the models and parameters are refined and predictive power of the model increases, better plans will be produced, significantly improving the therapeutic ratio.