Are fiducial markers useful surrogates when using respiratory gating to reduce motion of gastroesophageal junction tumors?

BACKGROUND: Radiation therapy (RT) is an integral component of the management of gastroesophageal junction (GEJ) tumors. We evaluated the use of implanted radiopaque fiducials as tumor surrogates to allow for more focal delivery of RT to these mobile tumors when using respiratory gating (RG) to reduce motion. MATERIAL AND METHODS: We analyzed four-dimensional computed tomography scans of 20 GEJ patients treated with RG and assessed correlation between tumor and implanted fiducial motion over the whole respiratory cycle and within a clinically realistic gate around end-exhalation. We evaluated fiducial motion concordance in 11 patients with multiple fiducials. RESULTS: Gating reduced anterior-posterior (AP) and superior-inferior (SI) mean tumor and fiducial motions by over 50%. Fiducials and primary tumor motions were moderately correlated: R(2) for AP and SI linear fits to the entire group were 0.54 and 0.68, respectively, but the correlation had strong inter-patient variation. For all patients with multiple fiducials, relative in-gate displacements were below 3 mm; results were similar for eight of 11 patients over the whole cycle. CONCLUSION: Implanted fiducial and gross tumor volume (GTV) motions correlate well but the correlation is patient-specific and may be dependent on the location of the fiducials with respect to the GTV.

Semi-automatic medical image segmentation with adaptive local statistics in Conditional Random Fields framework.

Planning radiotherapy and surgical procedures usually require onerous manual segmentation of anatomical structures from medical images. In this paper we present a semi-automatic and accurate segmentation method to dramatically reduce the time and effort required of expert users. This is accomplished by giving a user an intuitive graphical interface to indicate samples of target and non-target tissue by loosely drawing a few brush strokes on the image. We use these brush strokes to provide the statistical input for a Conditional Random Field (CRF) based segmentation. Since we extract purely statistical information from the user input, we eliminate the need of assumptions on boundary contrast previously used by many other methods, A new feature of our method is that the statistics on one image can be reused on related images without registration. To demonstrate this, we show that boundary statistics provided on a few 2D slices of volumetric medical data, can be propagated through the entire 3D stack of images without using the geometric correspondence between images. In addition, the image segmentation from the CRF can be formulated as a minimum s-t graph cut problem which has a solution that is both globally optimal and fast. The combination of a fast segmentation and minimal user input that is reusable, make this a powerful technique for the segmentation of medical images.

Interfractional anatomic variation in patients treated with respiration-gated radiotherapy.

As quality assurance for respiration-gated treatments using the Varian RPM system, we monitor interfractional diaphragm variation throughout treatment using extra anterior-posterior (AP) portal images. We measure the superior-inferior (SI distance between one or more bony landmarks and the ipsilateral diaphragm dome in each such radiograph and calculate its difference, D, from the corresponding distance in a planning CT scan digitally reconstructed radiograph (DRR). For each patient, the mean of D represents the systematic diaphragm displacement, and the standard deviation of D represents random diaphragm variations and is a measure of interfractional gating reproducibility. We present results for 31 sequential patients (21 lung, 10 liver tumors), each with at least 8 such portal images. For all patients, the gate included end-exhale. The patient-specific duty cycle ranged from 30% to 60%. All patients received customized audio prompting for simulation and treatment, and 14 patients also received visual prompting. Respiration-synchronized fluoroscopic movies taken at a conventional simulator revealed patient-specific diaphragm excursions from 1.0 cm to 5.0 cm and diaphragm excursion within the gate from 0.5 cm to 1.0 cm, demonstrating a significant reduction of intra-fractional diaphragm (and by inference tumor) motion by respiratory gating. One standard deviation of the systematic displacement (the mean of D) was 0.63 cm and 0.48 cm for the lung and liver patient groups, respectively. The average +/-1 SD of the random displacements (i.e., the average of the standard deviations of D) was 0.42 +/- 0.11 cm and 0.50 +/- 0.19 for the two groups, respectively. The similar magnitude of the systematic and random displacements suggests that both derive from a common distribution of interfractional variations. Combining visual with audio prompting did not significantly improve performance, as judged by D. Guided by these portal images, field changes were made during the course of treatment for 6 patients (1 lung, 5 liver).

Tumor motion control in the treatment of non small cell lung cancer.

Tumor motion due to respiration during radiation therapy for non-small cell lung cancer is a significant problem. This article reports on two techniques used to control tumor motion: respiratory gating and the deep inspiration breath hold technique. This technique was implemented in 40 patients without significant difficulties and there are encouraging clinical outcomes.

Dosimetric effect of respiratory motion in external beam radiotherapy of the lung.

BACKGROUND AND PURPOSE: To study the effect of breathing motion on gross tumor volume (GTV) coverage for lung tumors using dose-volume histograms and relevant dosimetric indices. PATIENTS AND METHODS: Treatment plans were chosen for 12 patients treated at our institution for lung carcinoma. GTV volumes of these patients ranged from 1.2 to 97.3 cm(3). A margin of 1-2 cm was used to generate the planning target volume (PTV). Additional margins of 0.6-1.0 cm were added to the PTV when designing treatment portals. For the purposes of TCP calculation, the prescription dose was assumed to be 70 Gy to remove the effects of prescription differences. Setup error was incorporated into the evaluation of treatment plans with a systematic component of sigma(RL) = 0.2 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.3 cm and a random component of sigma(RL) = 0.3 cm, sigma(AP) = 0.3 cm, and sigma(SI) = 0.3 cm. Breathing motion was incorporated into these plans based on an independent analysis of fluoroscopic movies of the diaphragm for 7 patients. The systematic component of breathing motion (sigma(RL) = 0.3 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.6 cm) was incorporated into the treatment plans on a slice by slice basis. The intrafractional component of breathing motion (sigma(RL) = 0.3 cm, sigma(AP) = 0.2 cm, and sigma(SI) = 0.6 cm) was incorporated by averaging the dose calculation over all displacements of the breathing cycle. Each patient was simulated 500 times to discern the range of possible outcomes. The simulations were repeated for a worst case scenario which used only breathing data with a large diaphragmatic excursion, both with and without intrafractional breathing motion. RESULTS: Dose to 95% of the GTV (D95), volume of the GTV receiving 95% of the prescription dose (V95) and TCP changed an average of -1.4+/-4.2, -1.0+/-3.3, and -1.4+/-3.8%, respectively, with the incorporation of normal breathing effects. In the worst case scenario (heavy breathers), D95 and V95 changed an average of -9.8+/-10.1 and -8.3+/-11.3%, respectively, and TCP changed by -8.1+/-9.1%. GTVs with volumes greater than 60 cm(3) showed stronger sensitivity to breathing especially if the shape was non-ellipsoidal. In the normal breathing case, the probability of a decrease in D95, V95, or TCP of a magnitude greater than 10% is less than 4%, and in the worse case scenario this probability is approximately 30-40% with intrafractional breathing motion included, and less than 10% with intrafractional breathing motion not included. CONCLUSIONS: With the PTV margins routinely used at our center, the effects of normal breathing on coverage are small on the average, with a less than 4% chance of a 10% or greater decrease in D95, V95, or TCP. However, in patients with large respiration-induced motion, the effect can be significant and efforts to identify such patients are important.

Deep inspiration breath hold and respiratory gating strategies for reducing organ motion in radiation treatment.

We examine 2 strategies for reducing respiration-induced organ motion in radiation treatment: deep inspiration breath hold (DIBH) and respiratory gating. DIBH is a controlled breathing technique in which the patient performs a supervised breath hold during treatment. The technique offers 2 benefits: reduced respiratory motion from the breath hold and increased normal tissue sparing from the increased lung volume. In respiratory-gated treatment, a device external to the patient monitors breathing and allows delivery of radiation only during certain time intervals, synchronous with the patient's respiratory cycle. Gated treatment offers reduced respiratory motion with less patient effort than DIBH. We briefly survey the development of these 2 strategies, describe their clinical implementation for treatment of thoracic and liver tumors at the Memorial Sloan-Kettering Cancer Center, and discuss their advantages and limitations.

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.

Evaluation of rapid dose map acquisition of a scanning liquid-filled ionization chamber electronic portal imaging device.

PURPOSE: We evaluated the performance of a new dosimetry module in the LC250 scanning liquid-filled ionization chamber (SLIC) electronic portal imaging device (EPID) for intensity-modulated radiotherapy (IMRT) verification. This module permits one to convert EPID readings to two-dimensional (2D) maps of IMRT dose rate in real time, and to integrate them over time to produce a profile of accumulated dose for treatment verification. METHODS AND MATERIALS: The EPID was calibrated using an iterative procedure, from which a lookup table for dose integration was generated and transferred to the image-acquisition hardware. To evaluate the EPID's integration capability, we investigated the linearity of imaging time (vs. monitor unit [MU]) and integrated dose (vs. planned dose) for static and IMRT fields, in both standard ( approximately 2.7 s/image) and fast ( approximately 1 s/image) synchronous acquisition modes (S- and F-modes). We also compared the EPID-measured profiles with that measured using film and ionization chamber, or calculated from the treatment planning system. For the EPID's patient dose verification capability, we compared the integrated central-axis (CAX) dose with the planned dose for 25 prostate IMRT fields. We also compared the measured relative profiles with the planned ones using a linear regression model, which returns an index sigma (root mean squared error) for the goodness of fit. We identified errors that are either associated with the timing of the EPID-start delay and end truncation, or with the integration process-detector memory effects (decrease in detector's sensitivity with time during the fast continuous acquisition) and beam hold-off effects (the withholding of linac beam pulses when multileaf collimator leaves are not in the correct positions). The CAX doses of static fields were corrected using the ratio of the irradiation time to the imaging time. A linear decay model was proposed to correct the detector memory effect. To investigate the beam hold-off effect, we verified the relative profiles of a five-field prostate IMRT plan for five different MU settings, and correlated the goodness of fit with the percent of beam hold-off. RESULTS: The imaging time is linearly proportional to the given MU with a slope of 0.250 MU/s (ideal slope is 0.250 MU/s) and a R(2) = 1.0. Although the R(2) of the linearity for the measured vs. planned dose is 1.0 for both modes, only the slopes for the S-mode are within 3% of unity. The slopes for the F-mode deviate from unity due to detector memory effects, and are accurately corrected using the linear decay model. The EPID measured profiles agree well (within 2.0%) with the planned dose and profiles for both modes. For the CAX dose of the 25 IMRT fields, the S-mode is within 2% of the planned dose, whereas the F-mode is off significantly (>3%) if not corrected for detector memory effects. For the relative profile verification, lower MU always produces higher sigma for the same mode. The F-mode is more accurate than the S-mode for the same MU; however, the improvement is not proportional to the difference in imaging speed. Analysis of the correlation of the goodness of fit with the percent of beam hold-off indicates that the accuracy of profile verification for the F-mode is predominantly determined by the beam hold-off effect for lower MU. CONCLUSION: The S-mode of LC250 combined with a large MU can be used for the pretreatment verification of IMRT beam delivery with a significant reduction of processing time and computer resources in comparison to off-line processing. Real-time verification during treatment requires the F-mode. Although the detector memory effects encountered in the F-mode can be compensated using the proposed linear decay model, sufficient accuracy for real-time verification requires a resolution of the beam hold-off problem.

Development of a semi-automatic alignment tool for accelerated localization of the prostate.

PURPOSE: Delivering high dose to prostate with external beam radiation has been shown to improve local tumor control. However, it has to be carefully performed to avoid partial target miss and delivering excessive dose to surrounding normal tissues. One way to achieve safe dose escalation is to precisely localize prostate immediately before daily treatment. Therefore, the radiation can be accurately delivered to the target. Once the prostate position is determined with high confidence, planning target volume (PTV) safety margin might be reduced for further reduction of rectal toxicity. A rapid computed tomography (CT)-based online prostate localization method is presented for this purpose. METHODS AND MATERIALS: Immediately before each treatment session, the patient is immobilized and undergoes a CT scan in the treatment position using a CT scanner situated in the treatment room. At the CT console, posterior, anterior, left, and right extents of the prostate are manually identified on each axial slice. The translational prostate displacements relative to the planned position are estimated by simultaneously fitting these identified extents from this CT scan to a template created from the finely sliced planning CT scan. A total of 106 serial CT scans from 8 prostate cancer patients were performed immediately before treatments and used to retrospectively evaluate the precision of this daily prostate targeting method. The three-dimensional displacement of the prostate with respect to its planned position was estimated. RESULTS: Five axial slices from each treatment CT scan were sufficient to produce a reliable correction when compared with prostate center of gravity (CoG) displacements calculated from physician-drawn contours. The differences (mean +/- SD) between these two correction schemes in the right-left (R/L), posterior-anterior (P/A), and superior-inferior (S/I) directions are 0.0 +/- 0.4 mm, 0.0 +/- 0.7 mm, and -0.4 +/- 1.9 mm, respectively. With daily CT extent-fitting correction, 97% of the scans showed that the entire posterior prostate gland was covered by PTV given a margin of 6 mm at the rectum-prostate interface and 10 mm elsewhere. In comparison, only 74% and 65% could be achieved by the corrections based on daily and weekly bony matching on portal images, respectively. CONCLUSIONS: Results show that daily CT extent fitting provides a precise correction of prostate position in terms of CoG. Identifying prostate extents on five axial CT slices at the CT console is less time-consuming compared with daily contouring of the prostate on many slices. Taking advantage of the prostate curvature in the longitudinal direction, this method also eliminates the necessity of identifying prostate base and apex. Therefore, it is clinically feasible and should provide an accelerated localization of the prostate immediately before daily treatment.

Time trends in organ position and volume in patients receiving prostate three-dimensional conformal radiotherapy.

Using multiple computed tomography (CT) scans, 50 patients undergoing prostate radiotherapy were tested for clinically significant time trends in the target and surrounding critical structures. Significant trends were observed toward increasing bladder volume and increasing bowel-to-planning target volume separation; however, no trends were observed in the prostate, seminal vesicles, or rectum. The subset of patients undergoing hormone therapy was also tested and did not independently exhibit any significant time trends.

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.