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V R Kini

Publications and source records attributed to V R Kini.

At least 19 recordsLinked to original sources

Is the diaphragm motion probability density function normally distributed?

During radiotherapy treatment planning, the margins given to the clinical target volume to form the planning target volume accounts for internal motion and set-up error. Most margin formulas assume that the underlying distributions are independent and normal. Clinical data suggests that the set-up error probability density function (pdf) can be considered to have an approximately normal distribution. However, there is evidence that internal motion does not have a normal distribution. Thus, in general, a convolution of the two pdfs should be performed to determine the total geometric error. The goals of this article were to (1) determine if the internal motion pdf due to respiration can be characterized using a normal distribution, and (2) if not, determine if the total geometric uncertainty for combining internal motion and set-up error can be characterized by a normal distribution. Sixty fluoroscopy diaphragm motion data sets were obtained using three breathing training types: free breathing, audio instruction, and visual feedback. Diaphragm motion was used as a surrogate for liver and lung cancer motion. The data were analyzed with normality tests in the following groups: (1) single motion measurements, (2) combined motion measurements for each patient, and (3) combined motion measurements for all patients. Following this analysis, the diaphragm motion pdfs were convolved with a set-up error pdf, and the standard deviation of the set-up error pdf at which the total geometric error pdf became normal was determined. At set-up error standard deviation values of at least 0.27 and 0.1 cm for free breathing, 0.57 and 0.42 cm for audio instruction, and 0.55 and 0 cm for visual feedback, for single motion measurements and combined motion measurements for each patient, respectively, total geometric error pdfs became approximately normal. When the motion measurements for all the patients were combined, diaphragm motion pdfs were approximately normal for all feedback types. Therefore, for treatment planning purposes in the absence of individual patient measurements, the diaphragm motion pdf can be considered an approximately normal distribution. However, care should be taken when determining a margin based on individual patients measurements as the total geometric error will, in general, not be normally distributed.

Artifacts↗

Predicting respiratory motion for four-dimensional radiotherapy.

Adapting radiation delivery to respiratory motion is made possible through corrective action based on real-time feedback of target position during respiration. The advantage of this approach lies with its ability to allow tighter margins around the target while simultaneously following its motion. A significant hurdle to the successful implementation of real-time target-tracking-based radiation delivery is the existence of a finite time delay between the acquisition of target position and the mechanical response of the system to the change in position. Target motion during the time delay leads to a resultant lag in the system's response to a change in tumor position. Predicting target position in advance is one approach to ensure accurate delivery. The aim of this manuscript is to estimate the predictive ability of sinusoidal and adaptive filter-based prediction algorithms on multiple sessions of patient respiratory patterns. Respiratory motion information was obtained from recordings of diaphragm motion for five patients over 60 sessions. A prediction algorithm that employed both prediction models-the sinusoidal model and the adaptive filter model-was developed to estimate prediction accuracy over all the sessions. For each session, prediction error was computed for several time instants (response time) in the future (0-1.8 seconds at 0.2-second intervals), based on position data collected over several signal-history lengths (1-7 seconds at 1-second intervals). Based on patient data included in this study, the following observations are made. Qualitative comparison of predicted and actual position indicated a progressive increase in prediction error with an increase in response time. A signal-history length of 5 seconds was found to be the optimal signal history length for prediction using the sinusoidal model for all breathing training modalities. In terms of overall error in predicting respiratory motion, the adaptive filter model performed better than the sinusoidal model. With the adaptive filter, average prediction errors of less than 0.2 cm (1sigma) are possible for response times less than 0.4 seconds. In comparing prediction error with system latency error (no prediction), the adaptive filter model exhibited lesser prediction errors as compared to the sinusoidal model, especially for longer response time values (>0.4 seconds). At smaller response time values (<0.4 seconds), improvements in prediction error reduction are required for both predictive models in order to maximize gains in position accuracy due to prediction. Respiratory motion patterns are inherently complex in nature. While linear prediction-based prediction models perform satisfactorily for shorter response times, their prediction accuracy significantly deteriorates for longer response times. Successful implementation of real-time target-tracking-based radiotherapy requires response times less than 0.4 seconds or improved prediction algorithms.

Algorithms↗

On the use of EPID-based implanted marker tracking for 4D radiotherapy.

Four-dimensional (4D) radiotherapy delivery to dynamically moving tumors requires a real-time signal of the tumor position as a function of time so that the radiation beam can continuously track the tumor during the respiration cycle. The aim of this study was to develop and evaluate an electronic portal imaging device (EPID)-based marker-tracking system that can be used for real-time tumor targeting, or 4D radiotherapy. Three gold cylinders, 3 mm in length and 1 mm in diameter, were implanted in a dynamic lung phantom. The phantom range of motion was 4 cm with a 3-s "breathing" period. EPID image acquisition parameters were modified, allowing image acquisition in 0.1 s. Images of the stationary and moving phantom were acquired. Software was developed to segment automatically the marker positions from the EPID images. Images acquired in 0.1 s displayed higher noise and a lower signal-noise ratio than those obtained using regular (> 1 s) acquisition settings. However, the markers were still clearly visible on the 0.1-s images. The motion of the phantom blurred the images of the markers and further reduced the signal-noise ratio, though they could still be successfully segmented from the images in 10-30 ms of computation time. The positions of gold markers placed in the lung phantom were detected successfully, even for phantom velocities substantially higher than those observed for typical lung tumors. This study shows that using EPID-based marker tracking for 4D radiotherapy is feasible, however, changes in linear accelerator technology and EPID-based image acquisition as well as patient studies are required before this method can be implemented clinically.

Artifacts↗

Acquiring a four-dimensional computed tomography dataset using an external respiratory signal.

Four-dimensional (4D) methods strive to achieve highly conformal radiotherapy, particularly for lung and breast tumours, in the presence of respiratory-induced motion of tumours and normal tissues. Four-dimensional radiotherapy accounts for respiratory motion during imaging, planning and radiation delivery, and requires a 4D CT image in which the internal anatomy motion as a function of the respiratory cycle can be quantified. The aims of our research were (a) to develop a method to acquire 4D CT images from a spiral CT scan using an external respiratory signal and (b) to examine the potential utility of 4D CT imaging. A commercially available respiratory motion monitoring system provided an 'external' tracking signal of the patient's breathing. Simultaneous recording of a TTL 'X-Ray ON' signal from the CT scanner indicated the start time of CT image acquisition, thus facilitating time stamping of all subsequent images. An over-sampled spiral CT scan was acquired using a pitch of 0.5 and scanner rotation time of 1.5 s. Each image from such a scan was sorted into an image bin that corresponded with the phase of the respiratory cycle in which the image was acquired. The complete set of such image bins accumulated over a respiratory cycle constitutes a 4D CT dataset. Four-dimensional CT datasets of a mechanical oscillator phantom and a patient undergoing lung radiotherapy were acquired. Motion artefacts were significantly reduced in the images in the 4D CT dataset compared to the three-dimensional (3D) images, for which respiratory motion was not accounted. Accounting for respiratory motion using 4D CT imaging is feasible and yields images with less distortion than 3D images. 4D images also contain respiratory motion information not available in a 3D CT image.

Algorithms↗

Quantifying the effect of intrafraction motion during breast IMRT planning and dose delivery.

Respiratory motion during intensity modulated radiation therapy (IMRT) causes two types of problems. First, the clinical target volume (CTV) to planning target volume (PTV) margin needed to account for respiratory motion means that the lung and heart dose is higher than would occur in the absence of such motion. Second, because respiratory motion is not synchronized with multileaf collimator (MLC) motion, the delivered dose is not the same as the planned dose. The aims of this work were to evaluate these problems to determine (a) the effects of respiratory motion and setup error during breast IMRT treatment planning, (b) the effects of the interplay between respiratory motion and multileaf collimator (MLC) motion during breast IMRT delivery, and (c) the potential benefits of breast IMRT using breath-hold, respiratory gated, and 4D techniques. Seven early stage breast cancer patient data sets were planned for IMRT delivered with a dynamic MLC (DMLC). For each patient case, eight IMRT plans with varying respiratory motion magnitudes and setup errors (and hence CTV to PTV margins) were created. The effects of respiratory motion and setup error on the treatment plan were determined by comparing the eight dose distributions. For each fraction of these plans, the effect of the interplay between respiratory motion and MLC motion during IMRT delivery was simulated by superimposing the respiratory trace on the planned DMLC leaf motion, facilitating comparisons between the planned and expected dose distributions. When considering respiratory motion in the CTV-PTV expansion during breast IMRT planning, our results show that PTV dose heterogeneity increases with respiratory motion. Lung and heart doses also increase with respiratory motion. Due to the interplay between respiratory motion and MLC motion during IMRT delivery, the planned and expected dose distributions differ. This difference increases with respiratory motion. The expected dose varies from fraction to fraction. However, for the seven patients studied and respiratory trace used, for no breathing, shallow breathing, and normal breathing, there were no statistically significant differences between the planned and expected dose distributions. Thus, for breast IMRT, intrafraction motion degrades treatment plans predominantly by the necessary addition of a larger CTV to PTV margin than would be required in the absence of such motion. This motion can be limited by breath-hold, respiratory gated, or 4D techniques.

Algorithms↗

Quantifying the predictability of diaphragm motion during respiration with a noninvasive external marker.

The aim of this work was to quantify the ability to predict intrafraction diaphragm motion from an external respiration signal during a course of radiotherapy. The data obtained included diaphragm motion traces from 63 fluoroscopic lung procedures for 5 patients, acquired simultaneously with respiratory motion signals (an infrared camera-based system was used to track abdominal wall motion). During these sessions, the patients were asked to breathe either (i) without instruction, (ii) with audio prompting, or (iii) using visual feedback. A statistical general linear model was formulated to describe the relationship between the respiration signal and diaphragm motion over all sessions and for all breathing training types. The model parameters derived from the first session for each patient were then used to predict the diaphragm motion for subsequent sessions based on the respiration signal. Quantification of the difference between the predicted and actual motion during each session determined our ability to predict diaphragm motion during a course of radiotherapy. This measure of diaphragm motion was also used to estimate clinical target volume (CTV) to planning target volume (PTV) margins for conventional, gated, and proposed four-dimensional (4D) radiotherapy. Results from statistical analysis indicated a strong linear relationship between the respiration signal and diaphragm motion (p<0.001) over all sessions, irrespective of session number (p=0.98) and breathing training type (p=0.19). Using model parameters obtained from the first session, diaphragm motion was predicted in subsequent sessions to within 0.1 cm (1 sigma) for gated and 4D radiotherapy. Assuming a 0.4 cm setup error, superior-inferior CTV-PTV margins of 1.1 cm for conventional radiotherapy could be reduced to 0.8 cm for gated and 4D radiotherapy. The diaphragm motion is strongly correlated with the respiration signal obtained from the abdominal wall. This correlation can be used to predict diaphragm motion, based on the respiration signal, to within 0.1 cm (1 sigma) over a course of radiotherapy.

Artifacts↗

Potential radiotherapy improvements with respiratory gating.

Gating is a relatively new and potentially useful therapeutic addition to external beam radiotherapy applied to regions affected by intra-fraction motion. The impact was of gating on treatment margins, image artifacts, and volume and positional accuracy was investigated by CT imaging of sinusoidally moving spheres. The motion of the spheres simulates target motion. During the CT imaging of dynamically moving spheres, gating reproduced the static volume to within 1%, whereas errors of over 20% were observed where gating was not used. Using a theoretical analysis of margins, gating alone or in combination with an electronic portal imaging device may allow a 2-11 mm reduction in the CTV to PTV margin, and thus less healthy tissue need be irradiated. Gating may allow a reduction of treatment margins, an improvement in image quality, and an improvement in positional and volumetric accuracy of the gross tumor volume.

Artifacts↗

The use of high-dose-rate brachytherapy alone after lumpectomy in patients with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: We present the preliminary results of our in-house protocol using outpatient high-dose-rate (HDR) brachytherapy as the sole radiation modality following lumpectomy in patients with early-stage breast cancer. METHODS AND MATERIALS: Thirty-seven patients with 38 Stage I-II breast cancers received radiation to the lumpectomy cavity alone using an HDR interstitial implant with (192)Ir. A minimum dose of 32 Gy was delivered on an outpatient basis in 8 fractions of 4 Gy to the lumpectomy cavity plus a 1- to 2-cm margin over consecutive 4 days. RESULTS: Median follow-up is 31 months. There has been one ipsilateral breast recurrence for a crude failure rate of 2.6% and no regional or distant failures. Wound healing was not impaired in patients undergoing an open-cavity implant. Three minor breast infections occurred, and all resolved with oral antibiotics. The cosmetic outcome was good to excellent in all patients. CONCLUSION: In selected patients with early-stage breast cancer, treatment of the lumpectomy cavity alone with outpatient HDR brachytherapy is both technically feasible and well tolerated. Early results are encouraging, however, longer follow-up is necessary before equivalence to standard whole-breast irradiation can be established and to determine the most optimal radiation therapy technique to be employed.

Aged↗

Motion adaptive x-ray therapy: a feasibility study.

Intrafraction motion caused by breathing requires increased treatment margins for chest and abdominal radiotherapy and may lead to 'motion artefacts' in dose distributions during intensity modulated radiotherapy (IMRT). Technologies such as gated radiotherapy may significantly increase the treatment time, while breath-hold techniques may be poorly tolerated by pulmonarily compromised patients. A solution that allows reduced margins and dose distribution artefacts, without compromising delivery time, is to synchronously follow the target motion by adapting the x-ray beam using a dynamic multileaf collimator (MLC), i.e. motion adaptive x-ray therapy, or MAX-T for short. Though the target is moving with time, in the MAX-T beam view the target is static. The MAX-T method superimposes the target motion due to respiration onto the beam originally planned for delivery. Thus during beam delivery the beam is dynamically changing position with respect to the isocentre using a dynamic MLC, the leaf positions of which are dependent upon the target position. Synchronization of the MLC motion and target motion occurs using respiration gated radiotherapy equipment. The concept and feasibility of MAX-T and the capability of the treatment machine to deliver such a treatment were investigated by performing measurements for uniform and IMRT fields using a mechanical sinusoidal oscillator to simulate target motion. Target dose measurements obtained using MAX-T for a moving target were found to be equivalent to those delivered to a static target by a static beam.

Feasibility Studies↗

Determining parameters for respiration-gated radiotherapy.

Respiration-gated radiotherapy for tumor sites affected by respiratory motion will potentially improve radiotherapy outcomes by allowing reduced treatment margins leading to decreased complication rates and/or increased tumor control. Furthermore, for intensity-modulated radiotherapy (IMRT), respiratory gating will minimize the hot and cold spot artifacts in dose distributions that may occur as a result of interplay between respiratory motion and leaf motion. Most implementations of respiration gating rely on the real time knowledge of the relative position of the internal anatomy being treated with respect to that of an external marker. A method to determine the amplitude of motion and account for any difference in phase between the internal tumor motion and external marker motion has been developed. Treating patients using gating requires several clinical decisions, such as whether to gate during inhale or exhale, whether to use phase or amplitude tracking of the respiratory signal, and by how much the intrafraction tumor motion can be decreased at the cost of increased delivery time. These parameters may change from patient to patient. A method has been developed to provide the data necessary to make decisions as to the CTV to PTV margins to apply to a gated treatment plan.

Algorithms↗

Active breathing control (ABC) for Hodgkin's disease: reduction in normal tissue irradiation with deep inspiration and implications for treatment.

PURPOSE: Active breathing control (ABC) temporarily immobilizes breathing. This may allow a reduction in treatment margins. This planning study assesses normal tissue irradiation and reproducibility using ABC for Hodgkin's disease. METHODS AND MATERIALS: Five patients underwent CT scans using ABC obtained at the end of normal inspiration (NI), normal expiration (NE), and deep inspiration (DI). DI scans were repeated within the same session and 1-2 weeks later. To simulate mantle radiotherapy, a CTV1 was contoured encompassing the supraclavicular region, mediastinum, hila, and part of the heart. CTV2 was the same as CTV1 but included the whole heart. CTV3 encompassed the spleen and para-aortic lymph nodes. The planning target volume (PTV) was defined as CTV + 9 mm. PTVs were determined at NI, NE, and DI. A composite PTV (comp-PTV) based on the range of NI and NE PTVs was determined to represent the margin necessary for free breathing. Lung dose-mass histograms (DMH) for PTV1 and PTV2 and cardiac dose-volume histograms (DVH) for PTV3 were compared at the three different respiratory phases. RESULTS: ABC was well-tolerated by all patients. DI breath-holds ranged from 34 to 45 s. DMHs determined for PTV1 revealed a median reduction in lung mass irradiated at DI of 12% (range, 9-24%; n = 5) compared with simulated free-breathing. PTV2 comparisons also showed a median reduction of 12% lung mass irradiated (range, 8-28%; n = 5). PTV3 analyses revealed the mean volume of heart irradiated decreased from 26% to 5% with deep inspiration (n = 5). Lung volume comparisons between intrasession and intersession DI studies revealed mean variations of 4%. CONCLUSION: ABC is well tolerated and reproducible. Radiotherapy delivered at deep inspiration with ABC may decrease normal tissue irradiation in Hodgkin's disease patients.

Heart↗

Improving the dosimetric coverage of interstitial high-dose-rate breast implants.

PURPOSE/OBJECTIVE: We performed a retrospective computed tomography (CT)-based three-dimensional (3D) dose-volume analysis of high-dose-rate (HDR) interstitial breast implants to evaluate the adequacy of lumpectomy cavity coverage, and then designed a simple, reproducible algorithm for dwell-time adjustment to correct for underdosage of the lumpectomy cavity. METHODS AND MATERIALS: Since March 1993, brachytherapy has been used as the sole radiation modality after lumpectomy in selected protocol patients with early-stage breast cancer treated with breast-conserving therapy. In this protocol, all patients received 32 Gy in 8 fractions of 4 Gy over 4 days. Eleven patients treated with HDR brachytherapy who underwent CT scanning after implant placement were included in this analysis. For each patient, the postimplant CT dataset was transferred to a 3D treatment planning system, and the relevant tissue volumes were outlined on each axial slice. The implant dataset, including the dwell positions and dwell times, were imported into the 3D planning system and then registered to the visible implant template in the CT dataset. The calculated dose distribution was analyzed with respect to defined volumes via dose-volume histograms. Due to the variability of lumpectomy cavity coverage discovered in this 3D quality assurance analysis, dwell times at selected positions were adjusted in an attempt to improve dosimetric coverage of the lumpectomy cavity. Using implant data from 5 cases, a dwell-time adjustment algorithm was designed and was then tested on 11 cases. In this algorithm, a point P was identified using axial CT images, which was representative of the underdosed region within the cavity. The distance (d) from point P to the nearest dwell position was measured. A number of dwell positions (N) nearest to point P were selected for dwell time adjustment. The algorithm was tested by increasing the dwell times of a variable number of positions (N = 1, 3, 5, 7, 10, and 20) by a weighting factor (alpha), where alpha = f(d) and alpha > 1, and subsequently performing 3D dose-volume analysis to evaluate the improvement in lumpectomy cavity coverage. RESULTS: Before adjustment in the 11 implants, the median proportion of the lumpectomy cavity and target volume that received at least the prescription dose was 85% and 68%, respectively. After dwell-time adjustment, lumpectomy cavity coverage was significantly improved in all 11 cases. The median distance from point P to the nearest dwell position (d) was 1.4 cm (range 0.9-1.9). The median volume of the lumpectomy cavity receiving 32 Gy increased from 85.3% in the actual implant to 97.0% (range 74-100%) by increasing the dwell time of a single dwell position by a median factor (alpha) of 12.2 according to the above algorithm. With N = 3, the median proportion of the cavity volume receiving 32 Gy was improved to 97.5% (range 77-100%), with a median alpha of 5.7. Further improvement in lumpectomy cavity coverage was relatively small by increasing additional dwell times. In addition, with N = 20, the median absolute volume of breast tissue receiving 150% of the prescription dose was 70.3 cm3 compared to 26.3 cm3 in the actual implant; whereas with N = 1 or N = 3, this median volume was only 35.9 and 42.0 cm3, respectively. CONCLUSION: Lumpectomy cavity coverage sometimes appears suboptimal with interstitial HDR breast brachytherapy using our current technique. A simple dwell-time increase at only 1-3 dwell positions can compensate for some underdosage without creating significant regions of overdosage. Using simple methodology, a single reference point representing the underdosed region can be utilized for initial selection of the dwell positions to be increased.

Algorithms↗

Dose-volume analysis for quality assurance of interstitial brachytherapy for breast cancer.

PURPOSE/OBJECTIVE: The use of brachytherapy in the management of breast cancer has increased significantly over the past several years. Unfortunately, few techniques have been developed to compare dosimetric quality and target volume coverage concurrently. We present a new method of implant evaluation that incorporates computed tomography-based three-dimensional (3D) dose-volume analysis with traditional measures of brachytherapy quality. Analyses performed in this fashion will be needed to ultimately assist in determining the efficacy of breast implants. METHODS AND MATERIALS: Since March of 1993, brachytherapy has been used as the sole radiation modality after lumpectomy in selected protocol patients with early-stage breast cancer treated with breast-conserving therapy. Eight patients treated with high-dose-rate (HDR) brachytherapy who had surgical clips outlining the lumpectomy cavity and underwent computed tomography (CT) scanning after implant placement were selected for this study. For each patient, the postimplant CT dataset was transferred to a 3D treatment planning system. The lumpectomy cavity, target volume (lumpectomy cavity plus a 1-cm margin), and entire breast were outlined on each axial slice. Once all volumes were entered, the programmed HDR brachytherapy source positions and dwell times were imported into the 3D planning system. Using the tools provided by the 3D planning system, the implant dataset was then registered to the visible implant template in the CT dataset. The distribution of the implant dose was analyzed with respect to defined volumes via dose-volume histograms (DVH). Isodose surfaces, the dose homogeneity index, and dosimetric coverage of the defined volumes were calculated and contrasted. All patients received 32 Gy to the entire implanted volume in 8 fractions of 4 Gy over 4 days. RESULTS: Three-plane implants were used for 7 patients and a two-plane implant for 1 patient. The median number of needles per implant was 16.5 (range 11-18). Despite visual verification by the treating physician that surgical clips (with an appropriate margin) were within the boundaries of the implant needles, the median proportion of the lumpectomy cavity that received the prescribed dose was only 87% (range 73-98%). With respect to the target volume, a median of only 68% (range 56-81%) of this volume received 100% of the prescribed dose. On average, the minimum dose received by at least 90% of the target volume was 22 Gy (range 17.3-26.9), which corresponds to 69% of the prescribed dose. CONCLUSION: Preliminary results using our new technique to evaluate implant quality with CT-based 3D dose-volume analysis appear promising. Dosimetric quality and target volume coverage can be concurrently analyzed, allowing the possibility of evaluating implants prospectively. Considering that target volume coverage may be suboptimal even after radiographically verifying accurate implant placement, techniques similar to this need to be developed to ultimately determine the true efficacy of brachytherapy in the management of breast cancer.

Brachytherapy↗

The use of active breathing control (ABC) to reduce margin for breathing motion.

PURPOSE: For tumors in the thorax and abdomen, reducing the treatment margin for organ motion due to breathing reduces the volume of normal tissues that will be irradiated. A higher dose can be delivered to the target, provided that the risk of marginal misses is not increased. To ensure safe margin reduction, we investigated the feasibility of using active breathing control (ABC) to temporarily immobilize the patient's breathing. Treatment planning and delivery can then be performed at identical ABC conditions with minimal margin for breathing motion. METHODS AND MATERIALS: An ABC apparatus is constructed consisting of 2 pairs of flow monitor and scissor valve, 1 each to control the inspiration and expiration paths to the patient. The patient breathes through a mouth-piece connected to the ABC apparatus. The respiratory signal is processed continuously, using a personal computer that displays the changing lung volume in real-time. After the patient's breathing pattern becomes stable, the operator activates ABC at a preselected phase in the breathing cycle. Both valves are then closed to immobilize breathing motion. Breathing motion of 12 patients were held with ABC to examine their acceptance of the procedure. The feasibility of applying ABC for treatment was tested in 5 patients by acquiring volumetric scans with a spiral computed tomography (CT) scanner during active breath-hold. Two patients had Hodgkin's disease, 2 had metastatic liver cancer, and 1 had lung cancer. Two intrafraction ABC scans were acquired at the same respiratory phase near the end of normal or deep inspiration. An additional ABC scan near the end of normal expiration was acquired for 2 patients. The ABC scans were also repeated 1 week later for a Hodgkin's patient. In 1 liver patient, ABC scans were acquired at 7 different phases of the breathing cycle to facilitate examination of the liver motion associated with ventilation. Contours of the lungs and livers were outlined when applicable. The variation of the organ positions and volumes for the different scans were quantified and compared. RESULTS: The ABC procedure was well tolerated in the 12 patients. When ABC was applied near the end of normal expiration, the minimal duration of active breath-hold was 15 s for 1 patient with lung cancer, and 20 s or more for all other patients. The duration was greater than 40 s for 2 patients with Hodgkin's disease when ABC was applied during deep inspiration. Scan artifacts associated with normal breathing motion were not observed in the ABC scans. The analysis of the small set of intrafraction scan data indicated that with ABC, the liver volumes were reproducible at about 1%, and lung volumes to within 6 %. The excursions of a "center of target" parameter for the livers were less than 1 mm at the same respiratory phase, but were larger than 4 mm at the extremes of the breathing cycle. The inter-fraction scan study indicated that daily setup variation contributed to the uncertainty in assessing the reproducibility of organ immobilization with ABC between treatment fractions. CONCLUSION: The results were encouraging; ABC provides a simple means to minimize breathing motion. When applied for CT scanning and treatment, the ABC procedure requires no more than standard operation of the CT scanner or the medical accelerator. The ABC scans are void of motion artifacts commonly seen on fast spiral CT scans. When acquired at different points in the breathing cycle, these ABC scans show organ motion in three-dimension (3D) that can be used to enhance treatment planning. Reproducibility of organ immobilization with ABC throughout the course of treatment must be quantified before the procedure can be applied to reduce margin for conformal treatment.

Feasibility Studies↗

A comprehensive review of prostate cancer brachytherapy: defining an optimal technique.

PURPOSE: A comprehensive review of prostate cancer brachytherapy literature was performed to determine if an optimal method of implantation could be identified, and to compare and contrast techniques currently in use. METHODS AND MATERIALS: A MEDLINE search was conducted to obtain all articles in the English language on prostate cancer brachytherapy from 1985 through 1998. Articles were reviewed and grouped to determine the primary technique of implantation, the method or philosophy of source placement and/or dose specification, the technique to evaluate implant quality, overall treatment results (based upon pretreatment prostate specific antigen, (PSA), and biochemical control) and clinical, pathological or biochemical outcome based upon implant quality. RESULTS: A total of 178 articles were identified in the MEDLINE database. Of these, 53 studies discussed evaluable techniques of implantation and were used for this analysis. Of these studies, 52% used preoperative ultrasound to determine the target volume to be implanted, 16% used preoperative computerized tomography (CT) scans, and 18% placed seeds with an open surgical technique. An additional 11% of studies placed seeds or needles under ultrasound guidance using interactive real-time dosimetry. The number and distribution of radioactive sources to be implanted or the method used to prescribe dose was determined using nomograms in 27% of studies, a least squares optimization technique in 11%, or not stated in 35%. In the remaining 26%, sources were described as either uniformly, differentially, or peripherally placed in the gland. To evaluate implant quality, 28% of studies calculated some type of dose-volume histogram, 21% calculated the matched peripheral dose, 19% the minimum peripheral dose, 14% used some type of CT-based qualitative review and, in 18% of studies, no implant quality evaluation was mentioned. Six studies correlated outcome with implant dose. One study showed an association of implant dose with the achievement of a PSA nadir < or = 0.5. Two studies showed an improvement in biochemical control with a D90 (dose to 90% of the prostate volume) of 120 to 140 Gy or higher, and 2 additional studies found an association of clinical outcome with implant dose. One study correlated implant quality with biopsy results. Of the articles, 33 discussed evaluable treatment results, but only 16 reported findings based upon pretreatment PSA and biochemical control. Three- to 5-year biochemical control rates ranged from 48% to 100% for pretreatment PSAs < or = 4, 55% to 90% for PSAs between 4 and 10, 30% to 89% for PSAs > 10, < or = 20 and < 10% to 100% for PSAs > 20. Due to substantial differences in patient selection criteria (e.g., median Gleason score, clinical stage, pretreatment PSA), number of patients treated, median follow-up, definitions of biochemical control, and time points for analysis, no single technique consistently produced superior results. CONCLUSIONS: Our comprehensive review of prostate cancer brachytherapy literature failed to identify an optimal treatment approach when studies were analyzed for treatment outcome based upon pretreatment PSA and biochemical control. Although several well-designed studies showed an improvement in outcome with total dose or implant quality, the numerous techniques for implantation and the varied and inconsistent methods to specify dose or evaluate implant quality suggest that standardized protocols should be developed to objectively evaluate this treatment approach. These protocols have recently been suggested and, when implemented, should significantly improve the reporting of treatment data and, ultimately, the efficacy of prostate brachytherapy.

Brachytherapy↗

The role of androgen deprivation in the definitive management of clinically localized prostate cancer treated with radiation therapy.

PURPOSE: Multiple studies exploring the use of androgen deprivation given in combination with radiotherapy (RT) for localized prostate cancer have reported significant improvements in the rates of local, regional, and biochemical control (BC). The impact of this therapeutic strategy on overall and cancer specific survival (CSS) has not been established, however. We performed a MEDLINE search of all available studies on this topic to determine if any conclusions could be reached on the efficacy of this treatment approach and the patients most suitable for its application. MATERIALS AND METHODS: A MEDLINE search was conducted to obtain all articles in the English language on the use of androgen deprivation in combination with RT for the treatment of localized prostate cancer. The medical subject headings (MeSH) used to search the MEDLINE database included: a) prostatic neoplasms; b) prostatic neoplasms/radiotherapy; c) prostatic neoplasms/androgen deprivation; d) hormone therapy; e) English; and f) 1980 to 1998. RESULTS: A total of 14 retrospective studies were identified that compared some form of androgen deprivation given in combination with RT. Most studies showed significant improvements in various measures of local/regional control and disease-free survival (DFS). Three of four studies that analyzed BC rates showed significant improvements in this endpoint but conflicting results were obtained for overall survival (OS). No study showed an improvement in CSS. Six prospective randomized trials were identified that directly compared RT with or without androgen deprivation. Again, all six studies showed improvements in some measure of local/regional control or DFS but only two studies showed an improvement in OS. One study reported a statistically significant improvement in CSS and another study showed an improvement in the rate of negative biopsies with combined treatment. CONCLUSIONS: When all available literature on androgen withdrawal given in combination with RT for the definitive treatment of localized prostate cancer was reviewed, no definite conclusions could be reached on the impact of this treatment approach on OS and CSS. However, local/regional control, DFS, and BC were almost uniformly improved with the use of androgen withdrawal suggesting that these impressive early results may translate into improved cure rates. Data from recently initiated and completed randomized trials will be needed, however, to define the impact of this approach on cancer specific mortality and the patients most suitable for it's use.

Androgen Antagonists↗

Use of three-dimensional radiation therapy planning tools and intraoperative ultrasound to evaluate high dose rate prostate brachytherapy implants.

PURPOSE: We performed a pilot study to evaluate the quality of high dose rate (HDR) prostate implants using a new technique combining intraoperative real-time ultrasound images with a commercially available 3-dimensional radiation therapy planning (3D RTP) system. METHODS AND MATERIALS: Twenty HDR prostate implants performed by four different physicians on a phase I/II protocol were evaluated retrospectively. Radiation therapy (RT) consisted of pelvic external beam RT (EBRT) to a dose of 46 Gy in 2-Gy fractions over 5 weeks and 2 HDR implants (prescribed dose of 950 cGy per implant). Our in-house real-time geometric optimization technique was used in all patients. Each HDR treatment was delivered without moving the patient. Ultrasound image sets were acquired immediately after needle placement and just prior to HDR treatment. The ultrasound image sets, needle and source positions and dwell times were imported into a commercial computerized tomography (CT) based 3D RTP system. Prostate contours were outlined manually caudad to cephalad. Dose-volume histograms (DVHs) of the prostate were evaluated for each implant. RESULTS: Four patients with stage T2a carcinoma, 4 with stage T2b, and 3 with stage T1c were studied. The median number of needles used per implant was 16 (range 14-18). The median treated volume of the implant (volume of tissue covered by the 100% isodose surface) was 82.6 cc (range 52.6-96.3 cc). The median target volume based on the contours entered in the 3D RTP system was 44.83 cc (range 28.5-67.45 cc). The calculated minimum dose to the target volume was 70% of the prescribed dose (range 45-97%). On average 92% of the target volume received the prescribed dose (range 75-99 %). The mean homogeneity index (fraction of the target volume receiving between 1.0 to 1.5 times the prescribed dose) was 80% or 0.8 (range 0.55-0.9). These results compare favorably to recent studies of permanent implants which report a minimum target volume dose of 43% (range 29-50%) and an average of 85% of the target volume (range 76-92%) receiving the prescribed dose. CONCLUSIONS: The feasibility of evaluating HDR prostate implants using ultrasound images (acquired immediately prior to treatment) with a commercially available 3D RTP system was established. The dosimetric characteristics of these HDR implants appear to be substantially different compared to permanent implants. These developments allow quantitative evaluation of the dosimetric quality of HDR prostate treatments. Future studies will examine any correlation between the dosimetric quality of the implant and clinical/biochemical outcomes.

Brachytherapy↗

Mammographic, pathologic, and treatment-related factors associated with local recurrence in patients with early-stage breast cancer treated with breast conserving therapy.

BACKGROUND: We retrospectively reviewed our institution's experience treating early-stage breast cancer patients with breast conserving therapy (BCT) to determine clinical, pathologic, mammographic, and treatment-related factors associated with outcome. METHODS: Between January 1980 and December 1987, 400 cases of Stage I and II breast cancer were managed with BCT at William Beaumont Hospital, Royal Oak, Michigan. All patients underwent at least an excisional biopsy. Radiation treatment consisted of delivering 45-50 Gy to the whole breast, followed by a boost to the tumor bed to at least 60 Gy in all patients. The median follow-up in the 292 surviving patients is 118 months. Multiple clinical, pathologic, mammographic, and treatment-related factors were analyzed for an association with local recurrence and survival. RESULTS: A total of 37 local recurrences developed in the treated breast, for a 5- and 10-year actuarial rate of 4% and 10%, respectively. On univariate analysis, patient age < or =35 years (25% vs. 7%, p = 0.004), and positive surgical margins (17% vs. 6%, p = 0.018) were associated with an increased risk of local recurrence at 10 years. On multivariate analysis, only age < or = 35 years remained significant. A subset analysis of 214 patients with evaluable mammographic findings was performed. On univariate analysis, age < or = 35 years (38% vs. 8%, p = 0.0029) and the presence of calcifications on preoperative mammography (22% vs. 6%, p = 0.0016) were associated with an increased risk of local recurrence. On multivariate analysis, both of these factors remained significant. The presence of calcifications on preoperative mammography did not affect the rates of overall survival, disease-free survival, and cause-specific survival. CONCLUSION: In patients with early-stage breast cancer treated with BCT, age < or = 35 years and calcifications on preoperative mammography appear to be associated with an increased risk of local recurrence.

Actuarial Analysis↗