Twyla R. Willoughby

Observations on Real-Time Prostate Gland Motion Using Electromagnetic Tracking

PURPOSE To quantify and describe the real-time movement of the prostate gland in a large data set of patients treated with radiotherapy. METHODS AND MATERIALS The Calypso four-dimensional localization system was used for target localization in 17 patients, with electromagnetic markers implanted in the prostate of each patient. We analyzed a total of 550 continuous tracking sessions. The fraction of time that the prostate was displaced by >3, >5, >7, and >10 mm was calculated for each session and patient. The frequencies of displacements after initial patient positioning were analyzed over time. RESULTS Averaged over all patients, the prostate was displaced >3 and >5 mm for 13.6% and 3.3% of the total treatment time, respectively. For individual patients, the corresponding maximal values were 36.2% and 10.9%. For individual fractions, the corresponding maximal values were 98.7% and 98.6%. Displacements >3 mm were observed at 5 min after initial alignment in about one-eighth of the observations, and increased to one-quarter by 10 min. For individual patients, the maximal value of the displacements >3 mm at 5 and 10 min after initial positioning was 43% and 75%, respectively. CONCLUSION On average, the prostate was displaced by >3 mm and >5 mm approximately 14% and 3% of the time, respectively. For individual patients, these values were up to three times greater. After the initial positioning, the likelihood of displacement of the prostate gland increased with elapsed time. This highlights the importance of initiating treatment shortly after initially positioning the patient.

Performance characterization of megavoltage computed tomography imaging on a helical tomotherapy unit

Helical tomotherapy is an innovative means of delivering IGRT and IMRT using a device that combines features of a linear accelerator and a helical computed tomography (CT) scanner. The HI-ART II can generate CT images from the same megavoltage x-ray beam it uses for treatment. These megavoltage CT (MVCT) images offer verification of the patient position prior to and potentially during radiation therapy. Since the unit uses the actual treatment beam as the x-ray source for image acquisition, no surrogate telemetry systems are required to register image space to treatment space. The disadvantage to using the treatment beam for imaging, however, is that the physics of radiation interactions in the megavoltage energy range may force compromises between the dose delivered and the image quality in comparison to diagnostic CT scanners. The performance of the system is therefore characterized in terms of objective measures of noise, uniformity, contrast, and spatial resolution as a function of the dose delivered by the MVCT beam. The uniformity and spatial resolutions of MVCT images generated by the HI-ART II are comparable to that of diagnostic CT images. Furthermore, the MVCT scan contrast is linear with respect to the electron density of material imaged. MVCT images do not have the same performance characteristics as state-of-the art diagnostic CT scanners when one objectively examines noise and low-contrast resolution. These inferior results may be explained, at least partially, by the low doses delivered by our unit; the dose is 1.1 cGy in a 20 cm diameter cylindrical phantom. In spite of the poorer low-contrast resolution, these relatively low-dose MVCT scans provide sufficient contrast to delineate many soft-tissue structures. Hence, these images are useful not only for verifying the patients position at the time of therapy, but they are also sufficient for delineating many anatomic structures. In conjunction with the ability to recalculate radiotherapy doses on these images, this enables dose guidance as well as image guidance of radiotherapy treatments.

The use of megavoltage CT (MVCT) images for dose recomputations.

Megavoltage CT (MVCT) images of patients are acquired daily on a helical tomotherapy unit (TomoTherapy, Inc., Madison, WI). While these images are used primarily for patient alignment, they can also be used to recalculate the treatment plan for the patient anatomy of the day. The use of MVCT images for dose computations requires a reliable CT number to electron density calibration curve. In this work, we tested the stability of the MVCT numbers by determining the variation of this calibration with spatial arrangement of the phantom, time and MVCT acquisition parameters. The two calibration curves that represent the largest variations were applied to six clinical MVCT images for recalculations to test for dosimetric uncertainties. Among the six cases tested, the largest difference in any of the dosimetric endpoints was 3.1% but more typically the dosimetric endpoints varied by less than 2%. Using an average CT to electron density calibration and a thorax phantom, a series of end-to-end tests were run. Using a rigid phantom, recalculated dose volume histograms (DVHs) were compared with plan DVHs. Using a deformed phantom, recalculated point dose variations were compared with measurements. The MVCT field of view is limited and the image space outside this field of view can be filled in with information from the planning kVCT. This merging technique was tested for a rigid phantom. Finally, the influence of the MVCT slice thickness on the dose recalculation was investigated. The dosimetric differences observed in all phantom tests were within the range of dosimetric uncertainties observed due to variations in the calibration curve. The use of MVCT images allows the assessment of daily dose distributions with an accuracy that is similar to that of the initial kVCT dose calculation.

Characterization and use of EBT radiochromic film for IMRT dose verification

We present an evaluation of a new and improved radiochromic film, type EBT, for its implementation to IMRT dose verification. Using a characterized flat bed color CCD scanner, the films dose sensitivity, uniformity, and speed of development post exposure were shown to be superior to previous types of radiochromic films. The films dose response was found to be very similar to ion chamber scans in water through comparisons of depth dose and lateral dose profiles. The effect of EBT film polarization with delivered dose and film scan orientation was shown to have a significant effect on the scanners OD readout. In addition, the films large size, flexibility, and the ability to submerge it in water for relatively short periods of time allowed for its use in both water and solid water phantoms to verify TomoTherapy IMRT dose distributions in flat and curved dose planes. Dose verification in 2D was performed on ten IMRT plans (five head and neck and five prostate) by comparing measured EBT dose distributions to TomoTherapy treatment planning system calculated dose. The quality of agreement was quantified by the gamma index for four sets of dose difference and distance to agreement criteria. Based on this study, we show that EBT film has several favorable features that allow for its use in routine IMRT patient-specific QA.

Short-course intensity-modulated radiotherapy for localized prostate cancer with daily transabdominal ultrasound localization of the prostate gland

PURPOSE To present our initial observations on the clinical feasibility of the technique of short-course intensity-modulated radiotherapy (SCIM-RT) in the treatment of localized prostate cancer coupled with daily transabdominal ultrasound localization of the prostate. The proposed regimen consists of a hypofractionated course delivering 70.0 Gy in 28 fractions. METHODS AND MATERIALS The treatment data of the first 51 patients treated with SCIM-RT at the Cleveland Clinic Foundation are presented in this report. The technique consisted of intensity-modulated radiotherapy using 5 static fields (anterior, 2 laterals, and 2 anterior obliques). Inverse plans were generated by the Corvus treatment-planning system. The treatment delivery was performed with a Varian Dynamic Multileaf Collimator. The target was the prostate only in patients with low-risk disease (stage T1-T2, pretreatment PSA < or =10, and biopsy Gleason < or =6). The target was the prostate and seminal vesicles in patients with high-risk disease (stage T3 or pretreatment PSA > 10 or biopsy Gleason > or =7). In the Corvus planning system, the margins for the planning target volume (PTV) were 4 mm posteriorly, 8 mm laterally, and 5 mm in all other directions. A total of 70.0 Gy (mean prostate dose approximately 75 Gy) was prescribed in all cases at 2.5 Gy per fraction to be delivered in 28 fractions over 5 1/2 weeks. Prior to treatment delivery, the patients were minimally immobilized on the treatment table, only using lasers and skin marks. The location of the prostate gland was verified daily with the BAT transabdominal ultrasound system and patient position adjustments were performed accordingly. Fifty-one patients completed therapy between October 1998 and May 1999. RESULTS The dose was prescribed to an isodose line ranging from 82.0% to 90.0% (mean: 87.2%). The range of the individual prostate mean doses was 73.5 to 78.5 Gy (average: 75.3 Gy). The range of the maximum doses was 77.4 to 84.5 Gy (average: 80.2 Gy). The range of the minimum doses was 64.3 to 69.2 Gy (average: 67.5 Gy). The average time for the prostate position verification and alignment of the prostate using the BAT system was 5 minutes. The entire localization/alignment process was performed by the radiation therapists. The daily alignment images were automatically saved and reviewed by the radiation oncologist, a process similar to port film checks. The total treatment (beam-on) time was around 6 minutes using the 5 static intensity-modulated fields. The mean and standard deviation (SD) of bladder volumes irradiated to 50, 60, and 70 Gy were as follows: 24 +/- 11 cc, 16 +/- 8 cc, and 8 +/- 6 cc. The mean and SD of rectal volumes irradiated to 50, 60, and 70 Gy were as follows: 22 +/- 11 cc, 15 +/- 8 cc, and 7 +/- 5 cc. The RTOG acute bladder toxicity scores were as follows: 0 in 3 (6%), 1 in 38 (74%), and 2 in 10 (20%). The RTOG acute rectal toxicity scores for SCIM-RT cases were as follows: 0 in 10 (20%), 1 in 33 (65%), and 2 in 8 (16%). No Grade 3 or 4 acute toxicities were observed. CONCLUSION The delivery of our proposed hypofractionated-schedule SCIM-RT in combination with daily target localization/alignment with the BAT transabdominal ultrasound system is clinically feasible. It is an alternative method of dose escalation in the treatment of localized prostate cancer. The proposed schedule would significantly increase convenience to patients due to the decrease in overall treatment time. Preliminary acute toxicity results are extremely encouraging. Long-term follow-up is needed to assess late complications and treatment efficacy.

Preliminary observations on biochemical relapse-free survival rates after short-course intensity-modulated radiotherapy (70 Gy at 2.5 Gy/fraction) for localized prostate cancer.

PURPOSE To compare the preliminary biochemical relapse-free survival rates between short-course intensity-modulated radiotherapy (SCIM-RT) delivering 70 Gy in 28 fractions and three-dimensional conformal radiotherapy (3D-CRT) delivering 78 Gy in 39 fractions. METHODS AND MATERIALS Between January 1998 and December 1999, 166 patients were treated with SCIM-RT and 116 with 3D-CRT. The SCIM-RT cases were treated to 70 Gy (2.5 Gy/fraction) using 5 intensity-modulated fields using a dynamic multileaf collimator. The BAT transabdominal ultrasound system was used for localization of the prostate gland in all SCIM-RT cases. The 116 3D-CRT cases were treated to 78.0 Gy (2.0 Gy/fraction). The study sample therefore comprised 282 cases; 70 Gy in 28 fractions is equivalent to 78 Gy in 39 fractions for late-reacting tissues, according to the linear-quadratic model. The median follow-up for all cases was 25 months (range 3-42). The median follow-up was 21 months for the SCIM-RT cases (range 3-31) and 32 months for the 3D-CRT cases (range 3-42). The follow-up period was shorter for the SCIM-RT cases, because SCIM-RT was started only in October 1998. Biochemical relapse was defined as 3 consecutive rising prostate-specific antigen levels after reaching a nadir. The analysis was then repeated with a more stringent definition of biochemical control: reaching and maintaining a prostate-specific antigen level of < or =0.5 ng/mL. Radiation Therapy Oncology Group toxicity scores were used to assess complications. RESULTS For the 282 patients, the biochemical relapse-free survival rate at 30 months was 91% (95% confidence interval 88-95%). The biochemical relapse-free survival rate at 30 months for 3D-CRT vs. SCIM-RT was 88% (95% confidence interval 82-94%) vs. 94% (95% confidence interval 91-98%), respectively. The difference was not statistically significant between the two treatment arms (p = 0.084). The multivariate time-to-failure analysis using the Cox proportional hazards model for clinical parameters showed the pretreatment prostate-specific antigen level (p <0.001) and biopsy Gleason score (p <0.001) to be the only independent predictors of biochemical relapse. Clinical T stage (p = 0.66), age (p = 0.15), race (p = 0.25), and neoadjuvant androgen deprivation (p = 0.66) were not independent predictors of biochemical failure. SCIM-RT showed only a trend toward a better outcome on multivariate analysis (p = 0.058). Late rectal toxicity was limited; the actuarial combined Grade 2 and 3 late rectal toxicity rate at 30 months was 5% for SCIM-RT vs. 12% for 3D-CRT (p = 0.24). Grade 3 late rectal toxicity (rectal bleeding requiring cauterization) occurred in a total of 10 patients. The actuarial Grade 3 late rectal toxicity rate at 30 months was 2% for the SCIM-RT cases and 8% for the 3D-CRT cases (p = 0.059). Late urinary toxicity was rare in both groups. CONCLUSION With the currently available follow-up period (< or =30 months), the hypofractionated intensity-modulated radiotherapy schedule of 70.0 Gy delivered at 2.5 Gy/fraction had a comparable biochemical relapse profile with the prior 3D-CRT schedule delivering 78.0 at 2.0 Gy/fraction. The late rectal toxicity profile has been extremely favorable. If longer follow-up confirms the favorable biochemical failure and low late toxicity rates, SCIM-RT will be an alternative and more convenient way of providing dose escalation in the treatment of localized prostate cancer.

Short-course intensity-modulated radiotherapy (70 GY at 2.5 GY per fraction) for localized prostate cancer: preliminary results on late toxicity and quality of life

PURPOSE To present our preliminary observations on the late toxicity and quality of life (QOL) of patients treated with short-course intensity-modulated radiotherapy (SCIM-RT). METHODS AND MATERIALS Fifty-one patients were treated with SCIM-RT at the Cleveland Clinic Foundation between October 1998 and May 1999. The technique consisted of intensity-modulated radiotherapy using 5 static fields (anterior, 2 laterals, and 2 anterior obliques). Inverse plans were generated by the Corvus treatment-planning system. The treatment delivery was performed with a dynamic multileaf collimator. A total of 70.0 Gy was prescribed in all cases at 2.5 Gy per fraction to be delivered in 28 fractions over 5 and a half weeks. The location of the prostate gland was verified and adjusted daily with the BAT transabdominal ultrasound system. The median follow-up was 18 months (range: 11 to 26 months). The Radiation Therapy Oncology Group (RTOG) scales were used to evaluate late toxicity. The Expanded Prostate Cancer Index Composite (EPIC) was used to evaluate QOL. A total of 24 patients completed the EPIC questionnaire at approximately 2 years after therapy (median time from treatment to questionnaire administration: 24 months; range: 21 to 26 months). The results from the EPIC questionnaires were compared to scores from 46 patients treated during the same time period with conformal radiotherapy (CRT) to 78 Gy at 2 Gy per fraction. RESULTS The dose was prescribed to an isodose line ranging from 82.0% to 90.0% (mean: 87.2%). The range of the individual prostate mean doses was 73.5 to 78.5 Gy (average: 75.3 Gy). To date, only 1 patient had Grade 1 late urinary toxicity. To date, only 4 patients had Grade 1 late rectal toxicity. No Grade 2 or 3 late urinary or rectal complications have occurred. The actuarial rectal bleeding rate observed at 18 months was 7%. There were no differences in scores from the urinary, bowel, hormonal, and overall QOL domains between SCIM-RT patients and patients treated with CRT. The overall physical and mental QOL scores were also nearly identical to scores reported for the general U.S. population. CONCLUSION Preliminary late toxicity results up to 2 years after SCIM-RT are encouraging, with a median follow-up of 18 months (range 11 to 26 months). Late toxicity assessed by the physicians using RTOG late toxicity scores has been excellent. QOL reported by the patients using the EPIC questionnaire reveals no difference between patients treated with high-dose CRT at standard fractionation and patients treated with SCIM-RT. SCIM-RT is an alternative method of dose escalation in the treatment of localized prostate cancer. The proposed schedule significantly increases convenience to patients due to the decrease in overall treatment time.

DOSIMETRIC CONSEQUENCES OF INTRAFRACTION PROSTATE MOTION

PURPOSE To analyze characteristics of intrafraction prostate motion, monitored using the Calypso system, and investigate dosimetric consequences of the motion for different clinical target volume (CTV) to planning target volume (PTV) margins. METHODS AND MATERIALS Motion characteristics were analyzed for 1,267 tracking sessions and 35 patients. Using prostate-PTV margins of 0, 1, 2, 3, and 5 mm, dose metrics for the prostate gland, bladder, and rectum were evaluated for scenarios including patient population, individual patients showing the greatest motion during the course of treatment, and the individual session with the largest overall movement. Composite dose distributions incorporating motion blurring were calculated by convolving static intensity-modulated radiotherapy plans with corresponding motion probability functions. RESULTS For prostate-PTV margins of 2 mm or greater, intrafraction motion did not compromise prostate dose coverage for either the patient population or individual patients. For the patient showing the largest overall movement, the prostate equivalent uniform dose was reduced by only 17.4 cGy (0.23%), and the minimum prostate dose remained greater than 95% of the nominal dose. For margins less than 2 mm, the prostate dose-volume histogram in the same patient was slightly compromised, and the equivalent uniform dose was reduced by 38.5 cGy (0.51%). Sparing of the bladder and rectum was improved substantially by reducing margins. CONCLUSIONS Although significant motion can be observed during individual fractions, the dosimetric consequences are insignificant during a typical course of radiotherapy (30-40 fractions) with CTV-PTV margins of 2 mm or greater provided that the Calypso system is applied for pretreatment localization. Further reduction of the margin is possible if intrafraction realignment is performed.

Dose/volume relationship of late rectal bleeding after external beam radiotherapy for localized prostate cancer: absolute or relative rectal volume?

PURPOSE The purpose of this study was to analyze predictors of late rectal bleeding after external-beam radiotherapy for localized prostate cancer, with a focus on the volume of rectum irradiated. MATERIALS AND METHODS One hundred twenty-eight patients were treated with external-beam radiotherapy at the Cleveland Clinic Foundation between January 1998 and June 1999. Conformal radiotherapy (CRT) was used to deliver 78 Gy at 2 Gy per fraction in 76 cases, and short-course intensity-modulated radiotherapy (SCIM-RT) was used to deliver 70 Gy at 2.5 Gy per fraction in 52 cases. All contours were determined by one physician. The rectum was outlined from 1 cm above the target structures to 1 cm below the target structures. The entire volume of the rectum, along with the outer rectal wall, was included. All cases had detailed planning parameters that specifically determined the rectal volume receiving the prescription dose (VrPr), that is, 78 Gy for CRT and 70 Gy for SCIM-RT, and the percent of rectal volume receiving the prescription dose (%VrPr). The RTOG scales were used to evaluate late toxicity. The median follow-up was 24 months for all cases (range, 3-34 months), 21 months for SCIM-RT cases (range, 11-26 months), and 28 months for CRT cases (range, 3-34 months). RESULTS To date, five patients have had grade 1 late rectal toxicity (one CRT case and four SCIM-RT cases), one patient had grade 2 late rectal toxicity (CRT), and three patients had grade 3 late rectal toxicity (all CRT cases). Because of the low number of events, the analysis was performed with all patients experiencing rectal bleeding grouped together. The actuarial rectal bleeding rates at 18 and 24 months were 6% and 8%, respectively. The actuarial rectal bleeding rates at 24 months were identical (8%) for both SCIM-RT and CRT. A multivariate analysis of the following parameters was performed to determine independent predictors of rectal bleeding: age (continuous variable), race (Caucasian vs African American), coverage of seminal vesicles (yes vs no), adjuvant androgen deprivation (yes vs no), technique (CRT vs SCIM-RT), Radiation Therapy Oncology Group acute rectal toxicity score (continuous variable), VrPr (continuous variable in cubic centimeters), and %VrPr (continuous variable). Only the VrPr (cubic centimeter) was an independent predictor of rectal bleeding; %VrPr was not. With different cut-off levels being used, a VrPr of 15 cm 3 was significant on univariate analysis; the actuarial rectal bleeding rates at 24 months for patients with a VrPr ≤ 15 cm 3 versus a VrPr > 15 cm 3 were 5% versus 22%, respectively. CONCLUSION In our study sample, which included both conformal and intensity-modulated radiotherapy patients, the volume of rectum receiving the prescribed radiation dose (the equivalent of 78 Gy) was an independent predictor of late rectal bleeding. The percent of rectal volume receiving the full dose was not. Using actual volume rather than percent volume also avoids the dependence on the extent of rectal volume contours. We recommend 15 cm 3 as the cut-off of the rectal volume not to exceed the prescription dose. The rectal bleeding rate at 2 years for cases with < 15 cm 3 receiving the full dose was only 5%.

An evaluation of intrafraction motion of the prostate in the prone and supine positions using electromagnetic tracking

PURPOSE To evaluate differences in target motion during prostate irradiation in the prone versus supine position using electromagnetic tracking to measure prostate mobility. MATERIALS/METHODS Twenty patients received prostate radiotherapy in the supine position utilizing the Calypso Localization System® for prostate positioning and monitoring. For each patient, 10 treatment fractions were followed by a session in which the patient was repositioned prone, and prostate mobility was tracked. The fraction of time that the prostate was displaced by >3, 5, 7, and 10mm was calculated for each patient, for both positions (400 tracking sessions). RESULTS Clear patterns of respiratory motion were seen in the prone tracks due to the influence of increased abdominal motion. Averaged over all patients, the prostate was displaced >3 and 5mm for 37.8% and 10.1% of the total tracking time in the prone position, respectively. In the supine position, the prostate was displaced >3 and 5mm for 12.6% and 2.9%, respectively. With both patient setups, inferior and posterior drifts of the prostate position were observed. Averaged over all prone tracking sessions, the prostate was displaced >3mm in the posterior and inferior directions for 11.7% and 9.5% of the total time, respectively. CONCLUSIONS With real-time tracking of the prostate, it is possible to study the effects of different setup positions on the prostate mobility. The percentage of time the prostate moved >3 and 5mm was increased by a factor of three in the prone versus supine position. For larger displacements (>7 mm) no difference in prostate mobility was observed between prone and supine positions. To reduce rectal toxicity, radiotherapy in the prone position may be a suitable alternative provided respiratory motion is accounted for during treatment. Acute and late toxicity results remain to be evaluated for both patient positions.