G Mageras

Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation

PURPOSE/OBJECTIVE This study evaluates the dosimetric benefits and feasibility of a deep inspiration breath-hold (DIBH) technique in the treatment of lung tumors. The technique has two distinct features--deep inspiration, which reduces lung density, and breath-hold, which immobilizes lung tumors, thereby allowing for reduced margins. Both of these properties can potentially reduce the amount of normal lung tissue in the high-dose region, thus reducing morbidity and improving the possibility of dose escalation. METHODS AND MATERIALS Five patients treated for non-small cell lung carcinoma (Stage IIA-IIIB) received computed tomography (CT) scans under 4 respiration conditions: free-breathing, DIBH, shallow inspiration breath-hold, and shallow expiration breath-hold. The free-breathing and DIBH scans were used to generate 3-dimensional conformal treatment plans for comparison, while the shallow inspiration and expiration scans determined the extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry, and for DIBH, modified slow vital capacity maneuvers. Planning target volumes (PTVs) for free-breathing plans included a margin for setup error (0.75 cm) plus a margin equal to the extent of tumor motion due to respiration (1-2 cm). Planning target volumes for DIBH plans included the same margin for setup error, with a reduced margin for residual uncertainty in tumor position (0.2-0.5 cm) as determined from repeat fluoroscopic movies. To simulate the effects of respiration-gated treatments and estimate the role of target immobilization alone (i.e., without the benefit of reduced lung density), a third plan is generated from the free-breathing scan using a PTV with the same margins as for DIBH plans. RESULTS The treatment plan comparison suggests that, on average, the DIBH technique can reduce the volume of lung receiving more than 25 Gy by 30% compared to free-breathing plans, while respiration gating can reduce the volume by 18%. The DIBH maneuver was found to be highly reproducible, with intra breath-hold reproducibility of 1.0 (+/- 0.9) mm and inter breath-hold reproducibility of 2.5 (+/- 1.6) mm, as determined from diaphragm position. Patients were able to perform 10-13 breath-holds in one session, with a comfortable breath-hold duration of 12-16 s. CONCLUSION Patients tolerate DIBH maneuvers well and can perform them in a highly reproducible fashion. Compared to conventional free-breathing treatment, the DIBH technique benefits from reduced margins, as a result of the suppressed target motion, as well as a decreased lung density; both contribute to moving normal lung tissue out of the high-dose region. Because less normal lung tissue is irradiated to high dose, the possibility for dose escalation is significantly improved.

Technical aspects of the deep inspiration breath-hold technique in the treatment of thoracic cancer

PURPOSE The goal of this paper is to describe our initial experience with the deep inspiration breath-hold (DIBH) technique in conformal treatment of non-small-cell lung cancer with particular emphasis on the technical aspects required for implementation. METHODS AND MATERIALS In the DIBH technique, the patient is verbally coached through a modified slow vital capacity maneuver and brought to a reproducible deep inspiration breath-hold level. The goal is to immobilize the tumor and to expand normal lung out of the high-dose region. A physicist or therapist monitors and records patient breathing during simulation, verification, and treatment using a spirometer with a custom computer interface. Examination of internal anatomy during fluoroscopy over multiple breath holds establishes the reproducibility of the DIBH maneuver for each patient. A reference free-breathing CT scan and DIBH planning scan are obtained. To provide an estimate of tumor motion during normal tidal breathing, additional scan sets are obtained at end inspiration and end expiration. These are also used to set the spirometer action levels for treatment. Patient lung inflation is independently verified over the course of treatment by comparing the distance from the isocenter to the diaphragm measured from the DIBH digitally reconstructed radiographs to the distance measured on the portal films. Patient breathing traces obtained during treatment were examined retrospectively to assess the reproducibility of the technique. RESULTS Data from the first 7 patients, encompassing over 250 treatments, were analyzed. The inferred displacement of the centroid of gross tumor volume from its position in the planning scan, as calculated from the spirometer records in over 350 breath holds was 0.02 +/- 0.14 cm (mean and standard deviation). These data are consistent with the displacements of the diaphragm (-0.1 +/- 0.4 cm; range, from -1.2 to 1.1 cm) relative to the isocenter, as measured on the (92) portal films. The latter measurements include the patient setup error. The patient averaged displacement of the tumor during free breathing, determined from the tumor displacement between end inspiration and end expiration, was 0.8 +/- 0.5 cm in both the superior-inferior and anterior-posterior directions and 0.1 cm (+/- 0.1 cm) medial-laterally. CONCLUSION Treatment of patients with the DIBH technique is feasible in a clinical setting. With this technique, consistent lung inflation levels are achieved in patients, as judged by both spirometry and verification films. Breathing-induced tumor motion is significantly reduced using DIBH compared to free breathing, enabling better target coverage.

Evaluation of respiratory movement during gated radiotherapy using film and electronic portal imaging

PURPOSE To evaluate the effectiveness of a commercial system(1) in reducing respiration-induced treatment uncertainty by gating the radiation delivery. METHODS AND MATERIALS The gating system considered here measures respiration from the position of a reflective marker on the patients chest. Respiration-triggered planning CT scans were obtained for 8 patients (4 lung, 4 liver) at the intended phase of respiration (6 at end expiration and 2 at end inspiration). In addition, fluoroscopic movies were recorded simultaneously with the respiratory waveform. During the treatment sessions, gated localization films were used to measure the position of the diaphragm relative to the vertebral bodies, which was compared to the reference digitally reconstructed radiograph derived from the respiration-triggered planning CT. Variability was quantified by the standard deviation about the mean position. We also assessed the interfraction variability of soft tissue structures during gated treatment in 2 patients using an amorphous silicon electronic portal imaging device. RESULTS The gated localization films revealed an interfraction patient-averaged diaphragm variability of 2.8 +/- 1.0 mm (error bars indicate standard deviation in the patient population). The fluoroscopic data yielded a patient-averaged intrafraction diaphragm variability of 2.6 +/- 1.7 mm. With no gating, this intrafraction excursion became 6.9 +/- 2.1 mm. In gated localization films, the patient-averaged mean displacement of the diaphragm from the planning position was 0.0 +/- 3.9 mm. However, in 4 of the 8 patients, the mean (over localization films) displacement was >4 mm, indicating a systematic displacement in treatment position from the planned one. The position of soft tissue features observed in portal images during gated treatments over several fractions showed a mean variability between 2.6 and 5.7 mm. The intrafraction variability, however, was between 0.6 and 1.4 mm, indicating that most of the variability was due to patient setup errors rather than to respiratory motion. CONCLUSIONS The gating system evaluated here reduces the intra- and interfraction variability of anatomy due to respiratory motion. However, systematic displacements were observed in some cases between the location of an anatomic feature at simulation and its location during treatment. Frequent monitoring is advisable with film or portal imaging.

Effect of respiratory gating on reducing lung motion artifacts in PET imaging of lung cancer

Positron emission tomography (PET) has shown an increase in both sensitivity and specificity over computed tomography (CT) in lung cancer. However, motion artifacts in the 18F fluorodioxydoglucose (FDG) PET images caused by respiration persists to be an important factor in degrading PET image quality and quantification. Motion artifacts lead to two major effects: First, it affects the accuracy of quantitation, producing a reduction of the measured standard uptake value (SUV). Second, the apparent lesion volume is overestimated. Both impact upon the usage of PET images for radiation treatment planning. The first affects the visibility, or contrast, of the lesion. The second results in an increase in the planning target volume, and consequently a greater radiation dose to the normal tissues. One way to compensate for this effect is by applying a multiple-frame capture technique. The PET data are then acquired in synchronization with the respiratory motion. Reduction in smearing due to gating was investigated in both phantoms and patient studies. Phantom studies showed a dependence of the reduction in smearing on the lesion size, the motion amplitude, and the number of bins used for data acquisition. These studies also showed an improvement in the target-to-background ratio, and a more accurate measurement of the SUV. When applied to one patient, respiratory gating showed a 28% reduction in the total lesion volume, and a 56.5% increase in the SUV. This study was conducted as a proof of principle that a gating technique can effectively reduce motion artifacts in PET image acquisition.

Fluoroscopic evaluation of diaphragmatic motion reduction with a respiratory gated radiotherapy system

We report on initial patient studies to evaluate the performance of a commercial respiratory gating radiotherapy system. The system uses a breathing monitor, consisting of a video camera and passive infrared reflective markers placed on the patients thorax, to synchronize radiation from a linear accelerator with the patients breathing cycle. Six patients receiving treatment for lung cancer participated in a study of system characteristics during treatment simulation with fluoroscopy. Breathing synchronized fluoroscopy was performed initially without instruction, followed by fluoroscopy with recorded verbal instruction (i.e., when to inhale and exhale) with the tempo matched to the patients normal breathing period. Patients tended to inhale more consistently when given instruction, as assessed by an external marker movement. This resulted in smaller variation in expiration and inspiration marker positions relative to total excursion, thereby permitting more precise gating tolerances at those parts of the breathing cycle. Breathing instruction also reduced the fraction of session times having irregular breathing as measured by the system software, thereby potentially increasing the accelerator duty factor and decreasing treatment times. Fluoroscopy studies showed external monitor movement to correlate well with that of the diaphragm in four patients, whereas time delays of up to 0.7 s in diaphragm movement were observed in two patients with impaired lung function. From fluoroscopic observations, average patient diaphragm excursion was reduced from 1.4 cm (range 0.7–2.1 cm) without gating and without breathing instruction, to 0.3 cm (range 0.2–0.5 cm) with instruction and with gating tolerances set for treatment at expiration for 25% of the breathing cycle. Patients expressed no difficulty with following instruction for the duration of a session. We conclude that the external monitor accurately predicts internal respiratory motion in most cases; however, it may be important to check with fluoroscopy for possible time delays in patients with impaired lung function. Furthermore, we observe that verbal instruction can improve breathing regularity, thus improving the performance of gated treatments with this system. PACS number(s): 87.53.–j, 87.62.+n

Respiratory gating for liver tumors: use in dose escalation.

Abstract Purpose: To determine the clinical impact of the Varian Real-Time Position Monitor (RPM) respiratory gating system for treatment of liver tumors. Methods and Materials: Ten patients with liver tumors were selected for evaluation of this passive system, which tracks motion of reflective markers mounted on the abdomen with an infrared-sensitive camera. At simulation, a fluoroscopic movie, breathing trace, and CT scans synchronized at end-expiration (E-E) and end-inspiration were acquired in treatment position using the RPM system. Organs and gross tumor volume were contoured on each CT. Each organ’s positional change between two scan sets was quantified by calculation of the center of volume shift and an “index coefficient,” defined as the volume common to the two versions of the organ to the volume included in at least one (intersection/union). Treatment dose was determined by use of normal tissue complication probability calculations and dose-volume histograms. Gated portal images were obtained to monitor gating reproducibility with treatment. Results: Eight patients received 177 treatments with RPM gating. Average superior-to-inferior (SI) diaphragm motion on initial fluoroscopy was reduced from 22.7 mm without gating to 5.1 mm with gating. Comparing end-inspiration to E-E CT scans, average SI movement of the right diaphragm was 11.5 mm vs. 2.2 mm for two E-E CT scans. For all organs, average E-I SI organ motion was 12.8 mm vs. 2.0 mm for E-E studies. Index coefficients were closer to 1.0 for E-E than end-inspiration scans, indicating gating reproducibility. The average SI displacement of diaphragm apex on gated portal images compared with DRR was 2.3 mm. Treatment was prolonged less than 10 minutes with gating. The reproducible decrease in organ motion with gating enabled reduction in gross tumor volume-to-planning target volume margin from 2 to 1 cm. This allowed for calculated dose increases of 7%–27% (median: 21.3%) in 6 patients and enabled treatment in 2. Conclusion: Gating of radiotherapy for liver tumors enables safe margin reduction on tumor volume, which, in turn, may allow for dose escalation.

Quantitation of respiratory motion during 4D-PET/CT acquisition

We report on the variability of the respiratory motion during 4D-PET/CT acquisition. The respiratory motion for five lung cancer patients was monitored by tracking external markers placed on the abdomen. CT data were acquired over an entire respiratory cycle at each couch position. The x-ray tube status was recorded by the tracking system, for retrospective sorting of the CT data as a function of respiration phase. Each respiratory cycle was sampled in ten equal bins. 4D-PET data were acquired in gated mode, where each breathing cycle was divided into ten 500 ms bins. For both CT and PET acquisition, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to their respiratory phases. The respiratory periods, and average amplitude within each phase bin, acquired in both modality sessions were then analyzed. The average respiratory motion period during 4D-CT was within 18% from that in the 4D-PET sessions. This would reflect up to 1.8% fluctuation in the duration of each 4D-CT bin. This small uncertainty enabled good correlation between CT and PET data, on a phase-to-phase basis. Comparison of the average-amplitude within the respiration trace, between 4D-CT and 4D- PET, on a bin-by-bin basis show a maximum deviation of approximately 15%. This study has proved the feasibility of performing 4D-PET/CT acquisition. Respiratory motion was in most cases consistent between PET and CT sessions, thereby improving both the attenuation correction of PET images, and co-registration of PET and CT images. On the other hand, in two patients, there was an increased partial irregularity in their breathing motion, which would prevent accurately correlating the corresponding PET and CT images.

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.

Application of fast simulated annealing to optimization of conformal radiation treatments

Applications of simulated annealing to the optimization of radiation treatment plans, in which a set of beam weights are iteratively adjusted so as to minimize a cost function, have been motivated by its potential for finding the global or near-global minimum among multiple minima. However, the method has been found to be slow, requiring several tens of thousands of iterations to optimize 50 to 100 variables. A technique to improve the efficiency for finding a solution is reported, which is generally applicable to the optimization of continuous variables. In previous applications of simulated annealing to treatment planning optimization, only one or two weights are varied each iteration. This approach is to change all weights simultaneously, using random changes that are initially large to coarsely sample the cost function, then are reduced with iteration to probe finer structure. The performance of different methods are compared in optimizing a plan for treatment of the prostate, in which the search space consists of 54 noncoplanar beams and the cost function is based on tumor control and normal tissue complication probabilities. The proposed method yields solutions with similar values of the cost function in only a fraction of the iterations compared either to a fixed single weight adjustment technique, or to a method which combines the Nelder and Mead downhill simplex simulated annealing.

Control, Correction, and Modeling of Setup Errors and Organ Motion

As advances in radiotherapy technology enable higher precision treatments, it becomes increasingly important to understand the factors that contribute to treatment uncertainty. The recent developments in imaging modalities and computer algorithms have made possible quantitative measurements of treatment uncertainties on statistically significant numbers of patients, which has led to new strategies for reducing as well as incorporating them into the treatment planning process. This article reviews the current literature on two sources of uncertainties deemed important in photon therapy, namely, patient localization (setup) errors and organ motion. In the area of patient localization there has been increasing work on protocols using electronic portal imaging devices to correct setup errors. These protocols are derived from probability analyses based on knowledge of setup errors for a population of patients in combination with defined clinical endpoints. Measurements of organ motion and methods to correct or control it have been more limited, due partly to the larger difficulties in imaging and motion characterization. We also review two paradigms for accounting for uncertainties in treatment plans: the conventional approach, which adds a margin around the tumor volume, and an alternative one, which includes uncertainties directly in the dose distributions of the tumor volume and nearby normal organs.