The effect of interobserver variability on transrectal ultrasonography-based postimplant dosimetry.

PURPOSE: To investigate interobserver variability in contouring the prostate on postimplant transrectal ultrasonography (TRUS) images and its effect on dosimetric parameters that quantify implant quality. METHODS AND MATERIALS: Twenty preplanned peripherally loaded prostate implants were performed using 125I seeds and spacers linked together in linear arrays that maintain precise seed spacing and prevent seeds from rotating about their longitudinal axis. A set of two-dimensional transverse images spaced at 0.50-cm intervals was obtained with a high-resolution TRUS probe at the conclusion of the procedure with the patient still under anesthesia. A high percentage of the seeds (> 85%) were localized based on their visible echoes. The remaining seeds were identified based on the known locations of the "missing" seeds in the arrays. Two experienced ultrasonographers and a prostate brachytherapist independently contoured the prostate on the postimplant TRUS images. The prostate volumes defined by each observer were used to calculate the minimal dose received by 90% of the prostate volume (D90) and the percentage of the prostate volume receiving 100% of the prescribed minimal peripheral dose (V100). The observers also contoured the prostate on six preimplant TRUS studies to compare the variability in defining the prostate on pre- and postimplant TRUS images. RESULTS: The mean postimplant prostate volumes ranged from 20.8 to 66.9 cm3 (median: 45.7 cm3). The standard deviations (SDs), which reflect the variation in the volumes of the three observers, ranged from 1.4% to 26.1% of the mean (median: 11%). Multiple pairwise comparisons showed that the prostate volumes delineated by observer 3 differed significantly from those of observers 1 and 2 (p < 0.003). The volumes of observers 1 and 2 were not significantly different (p > 0.5). The mean values of D90 ranged from 124.2 to 171.1 Gy (median: 154.7 Gy) having SDs that ranged from 0.6% to 24.4% of the mean D90 (median: 7.8%). The mean values of V100 ranged from 82.3% to 95.1% (median: 92.8%) having SDs that ranged from 0.4% to 11.2% of the mean V100 (median: 4.0%). The values of both D90 and V100 calculated from the volumes of observer 3 were significantly (p < 0.003) different from those of observers 1 and 2, which did not differ significantly (p > 0.5). There was less interobserver variability in contouring the preimplant TRUS volumes. The mean volumes ranged from 20.3 to 54.3 cm3 having SDs that ranged from 1.9% to 14.1% (median: 8.6%). CONCLUSIONS: Significant interobserver differences in delineating the prostate volume on postimplant TRUS images were observed; however, these differences were less than generally reported for postimplant CT images. The interobserver differences in contouring the prostate in both TRUS and CT images produced significant differences in the dosimetric parameters, D90 and V100.

Localization of linked 125I seeds in postimplant TRUS images for prostate brachytherapy dosimetry.

PURPOSE: To demonstrate that (125)I seeds can be localized in transrectal ultrasound (TRUS) images obtained with a high-resolution probe when the implant is performed with linked seeds and spacers. Adequate seed localization is essential to the implementation of TRUS-based intraoperative dosimetry for prostate brachytherapy. METHODS AND MATERIALS: Thirteen preplanned peripherally loaded prostate implants were performed using (125)I seeds and spacers linked together in linear arrays that prevent seed migration and maintain precise seed spacing. A set of two-dimensional transverse images spaced at 0.50-cm intervals were obtained with a high-resolution TRUS probe at the conclusion of the procedure with the patient still under anesthesia. The image set extended from 1.0 cm superior to the base to 1.0 cm inferior to the apex. The visible echoes along each needle track were first localized and then compared with the known construction of the implanted array. The first step was to define the distal and proximal ends of each array. The visible echoes were then identified as seeds or spacers from the known sequence of the array. The locations of the seeds that did not produce a visible echo were interpolated from their known position in the array. A CT scan was obtained after implantation for comparison with the TRUS images. RESULTS: On average, 93% (range, 86-99%) of the seeds were visible in the TRUS images. However, it was possible to localize 100% of the seeds in each case, because the locations of the missing seeds could be determined from the known construction of the arrays. Two factors complicated the interpretation of the TRUS images. One was that the spacers also produced echoes. Although weak and diffuse, these echoes could be mistaken for seeds. The other was that the number of echoes along a needle track sometimes exceeded the number of seeds and spacers implanted. This was attributed to the overall length of the array, which was approximately 0.5 cm longer than the center-to-center distance between the first and last seed owing to the finite length of the seeds at the ends of the array. When this occurred, it was necessary to disregard either the most distal or most proximal echo, which produced a 0.5-cm uncertainty in the location of the array in the axial direction. For these reasons, simply localizing the visible echoes in the TRUS images did not guarantee the reliable identification of the seeds. CONCLUSION: Our results have demonstrated that a high percentage (>85%) of the implanted (125)I seeds can be directly visualized in postimplant TRUS images when the seeds and spacers are linked to preclude seed migration and rotation and when the images are obtained with a high-resolution TRUS probe. Moreover, it is possible to localize 100% of the seeds with the mechanism of linked seeds because the locations of the missing seeds can be determined from the known construction of the arrays.

Salvage of suboptimal prostate seed implantation: Reimplantation of underdosed region of prostate base.

PURPOSE: To demonstrate how a suboptimal (125)I prostate implant can be salvaged by reimplantation. METHODS AND MATERIALS: A (125)I implant was preplanned to deliver 150 Gy to the prostate of a patient with early stage prostate cancer. A CT scan at 35 days postimplant indicated that V(100) and D(90) were 46% and 49 Gy, respectively. The cause was a systematic source placement error that left the base significantly underdosed. A reimplantation of the underdosed region was planned by superimposing a template grid onto the 35-day postimplant CT scan images and digitizing them into the treatment planning computer as if they were TRUS images. The reimplantation was carried out under fluoroscopy guidance so that the initial implant was visible. RESULTS: The reimplantation increased V(100) and D(90) to 98% and 201 Gy, respectively. The misplaced seeds resulted in a high dose to the apical region and urethra, which was further increased by the reimplantation. The patient experienced increased urinary morbidity, which was relieved by medication. CONCLUSION: It is feasible to salvage a suboptimal prostate seed implant by reimplanting the underdosed regions under fluoroscopy guidance based on a plan generated from the postimplant CT scan.

Factors predicting for urinary incontinence after prostate brachytherapy.

PURPOSE: To define risk factors that predict for urinary incontinence after (125)I prostate brachytherapy. METHODS AND MATERIALS: Urinary incontinence after (125)I prostate brachytherapy was evaluated using a patient self-assessment questionnaire based on the NCI Common Toxicity Criteria (version 2). Grade 0 is defined as no incontinence; Grade 1 incontinence occurs with coughing, sneezing, or laughing; Grade 2 is spontaneous incontinence with some control; and Grade 3 is no control. One hundred fifty-three patients received monotherapy (145 Gy) (125)I implants between October 1996 and December 2001, and 112 (75%) responded to our survey. Median follow-up was 47 months (range, 14-74 months). Patient characteristics included a preimplant prostate-specific antigen < or =10, Gleason score < or =6, and stage < or =T2b. CT-based postimplant dosimetry was analyzed approximately 30 days after the procedure, and dose-volume histograms of the prostate and the prostatic urethra were generated based on contoured volumes. Dosimetric parameters evaluated as predictive factors for incontinence included the prostate volume; total activity implanted; number of needles; number of seeds; seed activity; urethral D(5), D(10), D(25), D(50), D(75), and D(90) doses; prostate D(90) doses; and prostate V(100), V(200), and V(300). Clinical parameters evaluated included age, Gleason score, prostate-specific antigen, preimplant International Prostate Symptom Score (I-PSS), and length of follow-up. RESULTS: Urethral D(10) dose and preimplant I-PSS predicted for urinary incontinence on multivariate analysis (p = 0.002 and p = 0.003, respectively). Twenty-eight patients reported Grade 1 incontinence (26%), and 5 patients reported Grade 2 (5%). Patients with Grade 1 and 2 incontinence were analyzed together, because of the small number of patients who experienced Grade 2. No patients reported Grade 3 incontinence. Mean urethral D(10) was 314 +/- 78 Gy in patients with Grade 0 compared with 394 +/- 147 Gy in patients with Grades 1, 2 incontinence (p = 0.002). The incidence of incontinence doubled as the urethral D(10) dose increased above 450 Gy. Patients with Grade 0 had a mean preimplant I-PSS score of 6.6 +/- 4.5 compared with 10.0 +/- 6.4 for Grades 1, 2 (p = 0.003). A significant increase in the incidence of incontinence was noted when the preimplant I-PSS was greater than 15. No relationship was noted between incontinence and prostate volume, total activity implanted, or the number of needles used (p = 0.83, p = 0.89, p = 0.36, respectively). CONCLUSION: Urethral D(10) dose and preimplant I-PSS are predictive for patients at higher risk of urinary incontinence. To decrease the risk of this complication, an effort should be made to keep the urethral D(10) dose as close to the prescribed dose as possible, and the preimplant I-PSS should be thoroughly evaluated in an attempt to select patients with scores less than 15.

Is it necessary to eliminate the posterior dose margin in prostate brachytherapy to achieve an acceptably low risk of late rectal morbidity?

PURPOSE: The use of a posterior dose margin in (125)I prostate brachytherapy is controversial. The posterior margin is often eliminated to lower the risk of late rectal morbidity (Radiation Therapy Oncology Group protocols 9805 and P-0019), but this may compromise the posterior prostate dose coverage. The purpose of this work is to determine whether it is necessary to eliminate the posterior margin to achieve an acceptably low risk of Grade 2 (bleeding/ulceration) late rectal morbidity. METHODS AND MATERIALS: The present work is an extension of a previous study in which we reported the probability of Grade 2 late rectal morbidity (bleeding/ulceration) as a function of the maximum rectal dose. Here, we define the relationship between the maximum rectal dose and the width of the posterior dose margin. From this relationship, and the probability of late morbidity determined earlier, we assessed the probability of late rectal morbidity as a function of the width of the posterior dose margin. The present work was based on the preplans of 15 permanent (125)I prostate seed implants having volumes ranging from 19 to 78 cm(3). All used peripheral loading with (125)I sources in the range 0.35-0.45 mCi. The maximum rectal dose was taken to be the isodose line coincident with the posterior edge of the prostate. The maximum rectal dose and the corresponding margin width were determined from the isodose distribution. The sensitivity of the relationship between the maximum rectal dose and the margin width to the prostate volume, the seed density, and the distance of the most posterior seeds from the posterior edge of the prostate was investigated. RESULTS: The maximum rectal dose is directly proportional to the margin width. This relationship is relatively insensitive to the prostate volume and the seed density, but is sensitive to the location of the posterior seeds relative to the posterior edge of the gland. Moving the seeds from 5 mm to 3 mm from the edge typically increased the maximum rectal dose by 17%. With the posterior seeds 3 mm from the edge, the maximum rectal doses that corresponded to 1 mm, 2 mm, 3 mm, 4 mm, and 5 mm margins were 187 +/- 6 Gy, 222 +/- 8 Gy, 257 +/- 11 Gy, 292 +/- 14 Gy, and 327 +/- 17 Gy, respectively. The corresponding probabilities that a patient will experience late rectal morbidity are < or =1%, < or =2%, < or =3%, < or =5%, and < or =7%, respectively. CONCLUSIONS: Our results indicate that a 2-3-mm posterior dose margin can be used in prostate brachytherapy with a relatively low (2-3%) risk of Grade 2 (bleeding/ulceration) late rectal morbidity, provided the sources in the posterior row are implanted at least 3 mm from the edge of the prostate. A practical guideline is to keep the maximum rectal dose below 150% of the target dose.

Cholangiocarcinoma: the impact of tumor location and treatment strategy on outcome.

The purpose of this study was to evaluate how the outcome of patients with extrahepatic cholangiocarcinoma (EHBC) may have been influenced by tumor location and treatment selection. The primary endpoint of this study is overall survival (OS). Between January 1983 and December 1997, 221 patients with biliary tumors were evaluated at Thomas Jefferson University Hospital. Of these, 118 fit the inclusion criteria for this study. The extent of disease was assessed by computed tomography, percutaneous transhepatic cholangiography or endoscopic retrograde cholangiopancreatography, magnetic resonance imaging, and ultrasonography. All patients had histologic confirmation of malignancy. Roux-en Y, hepaticojejunostomy, or choledochojejunostomy followed surgical resection of the primary tumor. Palliative measure (PS) included biliary catheter placement without brachytherapy or external beam irradiation (RT). RT was delivered via high-energy photons. Intraluminal brachytherapy was performed via percutaneous biliary catheterization with iridium-192 ribbon sources. Chemotherapy consisted of either intravenous 5-fluorouracil alone or in combination with doxorubicin, mitomycin C, or paclitaxel. PS consisted of metal bile duct stent placement. Median follow-up time for the entire group was 102 months and 43 months for patients who were still alive at the conclusion of the study period. Patients with proximal tumors underwent resection (n = 5), surgery and RT (n = 23), RT only (n = 31), chemotherapy only (n = 6), or PS (n = 12). Patients with distal tumors were treated with surgical resection (n = 17) or a combination of surgery and RT (n = 13), RT only (n = 6), or PS (n = 4). Median survival time (MST) for all 118 patients was 22 months. The MST for patients with distal tumors was 47 months versus 17 months for those with proximal tumors. The MST has not been reached for patients with distal EHBC treated with surgical resection and postoperative RT, whereas the median survival for those treated with surgery alone is 62.5 months. However, 4 of 17 of these patients had in situ carcinoma. Six patients had distal tumors treated with RT only with a MST of 6 months. Patients with proximal tumors treated with surgery and RT had a superior OS at 5 years compared to patients treated with RT alone (24 vs. 13 months; p = 0.007). There was an improved OS in patients with proximal tumors treated with surgical resection and RT compared to surgery alone (p = 0.023). There is no discernable influence of chemotherapy on outcome in patients with proximal EHBC. The MST for patients treated with PS was 3.5 months. Surgery and postoperative RT appear to be better than either surgery or RT alone in patients with proximal EHBC. In patients with distal EHBC, the addition of resection and RT appears to offer an advantage, which is increasingly apparent with longer follow-up time. The prognosis remains dismal for patients treated with palliative intent.

Impact of oedema on implant geometry and dosimetry for temporary high dose rate brachytherapy of the prostate.

The optimal timing of dosimetry for permanent seed prostatic implants remains contentious given the half life of post-implant oedema resolution. The aim of this study was to establish whether prostatic oedematous change over the duration of a temporary high dose rate (HDR) interstitial brachytherapy (BR) boost would result in significant needle displacement, and whether this change in geometry would influence dosimetry. Two CT scans, one for dosimetric purposes on the day of the implant and the second just prior to implant removal, were obtained for four patients receiving transperineal interstitial prostate brachytherapy. The relative changes in cross-sectional dimensions of the implants were calculated by establishing the change in mean radial distance (MRD) of the needle positions from the geometric centre of the implant for each patient's pair of CT studies. The treatment plan, as calculated from the first CT scan, was used in the second set of CT images to allow a comparison of dose distribution. The percentage change in MRD over the duration of the temporary implants ranged from -1.91% to 1.95%. The maximum change in estimated volume was 3.94%. Dosimetric changes were negligible. In the four cases studied, the degree of oedematous change and consequent displacement of flexiguide needle positions was negligible and did not impact on the dosimetry. The rate and direction of oedematous change can be extremely variable but on the basis of the four cases studied and the results of a larger recent study, it might not be necessary to re-image patients for dosimetric purposes over the duration of a fractionated HDR BT boost to the prostate where flexiguide needles are utilized. Nevertheless, further investigation with larger patient numbers is required.

Probability of late rectal morbidity in 125I prostate brachytherapy.

PURPOSE: Rectal toxicity is a concern in prostate brachytherapy because it is difficult to avoid delivering a dose equal to, or greater than, the prescription dose to the anterior surface of the rectum. The purpose of this study was to define the probability that a patient will experience Grade 2 (bleeding/ulceration) late rectal morbidity after 125I prostate brachytherapy according to the rectal dosimetry. METHODS AND MATERIALS: Ninety-eight consecutive patients who received monotherapy 125I prostate implants for treatment of Stage T1-T2, favorable-risk adenocarcinoma of the prostate were evaluated for Radiation Therapy Oncology Group Grade 2 late rectal morbidity. All reported incidences of late morbidity were retrospectively confirmed by colonoscopy. All patients had at least 15 months follow-up after implantation. The median follow-up was 32 months (range 15-54). The rectal dosimetry was based on a CT scan obtained at 3-9 weeks after implantation. The rectum was contoured on each CT image between the base and apex of the prostate. A dose-surface histogram was compiled for each implant, and the relative surface area that received a dose > or =100, > or =150, > or =200, > or =300, > or =400, and > or =500 Gy was recorded. The probability of developing late rectal toxicity was calculated by logistic regression analysis as a function of dose and the percentage of the rectal surface that received that dose. RESULTS: Of the 98 patients, 10 developed Grade 2 late rectal morbidity. The percentage of the rectal surface that received 100, 150, 200, and 300 Gy was significantly greater (p < or =0.02) for patients who experienced late rectal morbidity. The probability of late rectal morbidity increased with both the dose and the percentage of the rectal surface that received that dose. The probability was < or =1% when 20%, 7%, and 0% of the rectal surface received 100, 150, and 200 Gy, respectively. The probability increased to < or =5% when 31%, 19%, and 9% of the rectal surface received these doses. The probability of late rectal morbidity can also be expressed in terms of the maximal rectal dose. The probability of late morbidity was 0.4%, 1.2%, and 4.7% when the maximal rectal dose was 150, 200, and 300 Gy, respectively. CONCLUSION: The percentage of the rectal surface that receives a dose > or =100 Gy is predictive of Grade 2 (bleeding/ulceration) late rectal morbidity after 125I prostate brachytherapy. The probability of late morbidity depends on both the dose and the percentage of the rectal surface that received that dose. Our results indicate that the rectum can tolerate doses of 100, 150, and 200 Gy to approximately 30%, 20%, and 10% of the rectal surface with a < or =5% risk of late morbidity. Our results also indicate that the practical guideline for limiting the incidence of late morbidity to 1%, 3%, or 5% is to keep the maximal rectal dose to <200, 250, and 300 Gy, respectively.

A detailed examination of the difference between planned and treated margins in 125I permanent prostate brachytherapy.

PURPOSE: To determine whether potential extraprostatic extension (EPE) of prostate adenocarcinoma is covered by the prescribed dose when permanent 125I implants are planned with a 5-mm treatment margin. METHODS AND MATERIALS: The postimplant dosimetry of 60 consecutive 125I prostate implants was analyzed to determine whether there was a residual 3-mm margin, adequate for treatment of potential EPE. The implants were peripherally loaded and planned with a nominal 5-mm symmetric dose margin. Extraprostatic seeds were not used at midgland, although extraprostatic seeds were placed at the base and apex. The radial distance between the edge of the prostate and the prescription isodose line (145 Gy) was measured at the left lateral, left posterolateral, posterior, right posterolateral, and right lateral positions at the base, midgland, and apex in both the preplan and postimplant dosimetry. RESULTS: The mean postimplant margin at the base (4 +/- 2 mm) was significantly less (p < 0.01) than planned (6 +/- 2 mm) by 2 mm. The planned and postimplant margins at the midgland (5 +/- 1 mm and 5 +/- 2 mm) and apex (7 +/- 2 mm and 7 +/- 3 mm) were indistinguishable (p = 0.31 and p = 0.69, respectively). At the base, 69% of the measurements were > or = 3 mm compared with 89% and 91% at the midgland and apex, respectively. Overall, 83% of the margin measurements were > or = 3 mm. The prostate postimplant V100 and D90 were 96 +/- 4% and 193 +/- 27 Gy, respectively. CONCLUSIONS: A 5-mm planning dose margin can potentially treat most EPE. However, the postimplant margin, like other dosimetric parameters, is sensitive to source placement errors and the percentage of EPE treated depends upon how well the plan is executed. Because implant quality is operator dependent, we would not recommend brachytherapy alone for patients with a high risk of EPE.

Impact of postimplant edema on V(100) and D(90) in prostate brachytherapy: can implant quality be predicted on day 0?

PURPOSE: To determine the effect of edema on the dosimetric parameters V(100) (percentage of prostate volume that received a dose equal to or greater than the prescribed dose) and D(90) (minimal dose delivered to 90% of prostate volume) in 125I prostate brachytherapy and to determine whether the edema can be used to predict implant quality on the day of the implant (Day 0). METHODS AND MATERIALS: Fifty consecutive patients treated with (125)I implants who had two postimplant CT scans were selected for this study. The mean interval between the studies was 46 +/- 23 days. The implants were preplanned to deliver 150 Gy to the prostate plus a 3-5-mm symmetric dose margin using peripherally loaded 0.4-0.6-mCi (NIST-99) (125)I seeds. A dose-volume histogram was compiled for each postimplant CT scan. The V(100) and D(90) from the first and second CT scans were compared to determine the effect of edema on these parameters. A multivariate regression analysis was performed to define the linear relationships for predicting the V(100) or D(90) at 30-60 days after implant from the magnitude of the edema and the values of V(100) and D(90) on Day 0. RESULTS: V(100) and D(90) increased by 5% +/- 6% and 15% +/- 17%, respectively, during the interval between the first and second postimplant CT scans. The mean edema was 1.53 +/- 0.20. The increases in V(100) and D(90) were found to be proportional to the edema and the values of V(100) and D(90) on Day 0. The increase in V(100) was also found to depend on the width of the preplan dose margin. Linear relationships were derived that predict the V(100) and D(90) at 30-60 days after implant with a standard error of +/-4% and +/-24 Gy, respectively. CONCLUSION: V(100) and D(90) increased by 5% +/- 6% and 15% +/- 17%, respectively, during the first 30-60 days after implant. The results of a multivariate linear regression analysis showed that the increases in V(100) and D(90) were proportional to both the magnitude of the edema and the values of these parameters on Day 0. The relationships derived by linear regression analysis predict V(100) and D(90) at 30-60 days after implant to within +/-4% and +/-24 Gy, respectively. However, predicting the 30-60-day V(100) and D(90) on Day 0 is a poor substitute for obtaining a 30-60-day CT scan, because the uncertainty in the predicted values is greater by a factor of > or =2. Nevertheless, on average, the predicted values should provide a more reliable estimate of the actual V(100) and D(90) than the Day 0 values that ignore the effect of edema altogether. The increase in V(100) was also found to depend on the width of the preplan dose margin; therefore, our results for V(100) are only valid for implants planned with a 3-5-mm margin.