The aim was to determine the incidence of seed migration not only to the chest, but also to the abdomen and pelvis after transperineal interstitial prostate brachytherapy with loose 125I seeds.
We reviewed the records of 267 patients who underwent prostate brachytherapy with loose 125I seeds. After seed implantation, orthogonal chest radiographs, an abdominal radiograph, and a pelvic radiograph were undertaken routinely to document the occurrence and sites of seed migration. The incidence of seed migration to the chest, abdomen, and pelvis was calculated. All patients who had seed migration to the abdomen and pelvis subsequently underwent a computed tomography scan to identify the exact location of the migrated seeds. Postimplant dosimetric analysis was undertaken, and dosimetric results were compared between patients with and without seed migration.
A total of 19,236 seeds were implanted in 267 patients. Overall, 91 of 19,236 (0.47%) seeds migrated in 66 of 267 (24.7%) patients. Sixty-nine (0.36%) seeds migrated to the chest in 54 (20.2%) patients. Seven (0.036%) seeds migrated to the abdomen in six (2.2%) patients. Fifteen (0.078%) seeds migrated to the pelvis in 15 (5.6%) patients. Seed migration occurred predominantly within two weeks after seed implantation. None of the 66 patients had symptoms related to the migrated seeds. Postimplant prostate D90 was not significantly different between patients with and without seed migration.
We showed the incidence of seed migration to the chest, abdomen and pelvis. Seed migration did not have a significant effect on postimplant prostate D90.
Brachytherapy; 125I; Migration; Prostate cancer; Seed
We evaluated the post-operative pattern of prostate volume (PV) changes following prostate brachytherapy (PB) and analyzed variables which affect swelling.
Material and methods
Twenty-nine patients treated with brachytherapy (14) or combined brachytherapy and external beam radiotherapy modality (15) underwent pre- and post-implant computed tomography (CT). Prostate volume measurements were done on post-operative days 1, 9, 30, and 60. An observer performed 139 prostate volume (PV) measurements. We analyzed the influence of pre-implant PV, number of needles and insertion attempts, number and activity of seeds, Gleason score, use of hormonal therapy and external beam radiation therapy on the extent of edema. We computed a volume correction factor (CF) to account for dosimetric changes between day 1 and day 30. Using the calculated CF, the dose received by 90% (D90) of the prostate on day 30 (D90Day30) was obtained by dividing day 1 (D90Day1) by the CF.
The mean PV recorded on post-operative day 1 was 67.7 cm3, 18.8 cm3 greater than average pre-op value (SD 15.6 cm3). Swelling returned to pre-implant volume by day 30. Seed activity, treatment modality, and Gleason score were significant variables. The calculated CF was 0.76. After assessment using the CF, the mean difference between estimated and actual D90Day30 was not significant.
We observed maximum prostate size on post-operative day 1, returning to pre-implant volume by day 30. This suggests that post-implant dosimetry should be obtained on or after post-operative day 30. If necessary, day 30 dosimetry can be estimated by dividing D90Day1 by a correction factor of 0.76.
prostate brachytherapy; post-implant dosimetry; computed brachytherapy
The present study compared the difference between intraoperative transrectal ultrasound (iTRUS)-based prostate volume and preplan computed tomography (CT), preplan magnetic resonance imaging (MRI)-based prostate volume to estimate the number of seeds needed for appropriate dose coverage in permanent brachytherapy for prostate cancer.
Materials and Methods
Between March 2007 and March 2011, among 112 patients who underwent permanent brachytherapy with 125I, 60 image scans of 56 patients who underwent preplan CT (pCT) or preplan MRI (pMRI) within 2 months before brachytherapy were retrospectively reviewed. Twenty-four cases among 30 cases with pCT and 26 cases among 30 cases with pMRI received neoadjuvant hormone therapy (NHT). In 34 cases, NHT started after acquisition of preplan image. The median duration of NHT after preplan image acquisition was 17 and 21 days for cases with pCT and pMRI, respectively. The prostate volume calculated by different modalities was compared. And retrospective planning with iTRUS image was performed to estimate the number of 125I seed required to obtain recommended dose distribution according to prostate volume.
The mean difference in prostate volume was 9.05 mL between the pCT and iTRUS and 6.84 mL between the pMRI and iTRUS. The prostate volume was roughly overestimated by 1.36 times with pCT and by 1.33 times with pMRI. For 34 cases which received NHT after image acquisition, the prostate volume was roughly overestimated by 1.45 times with pCT and by 1.37 times with pMRI. A statistically significant difference was found between preplan image-based volume and iTRUS-based volume (p < 0.001). The median number of wasted seeds is approximately 13, when the pCT or pMRI volume was accepted without modification to assess the required number of seeds for brachytherapy.
pCT-based volume and pMRI-based volume tended to overestimate prostate volume in comparison to iTRUS-based volume. To reduce wasted seeds and cost of the brachytherapy, we should take the volume discrepancy into account when we estimate the number of 125I seeds for permanent brachytherapy.
Brachytherapy; Prostate cancer; Prostate volume
To determine prostate volume (Pvol) changes at 3 different time points during the course of I125 permanent seed brachytherapy (PB). To assess the impact of these changes on acute urinary retention (AUR) and dosimetric outcome.
We analyzed 149 hormone-naïve patients. Measurements of the prostate volume were done using three-dimensional transrectal ultrasound (3D-TRUS) in the operating room before insertion of any needle (V1), after the insertion of 2 fixation needles with a harpoon (V2) and upon completion of the implant (V3). The quality of the implant was analyzed with the D90 (minimum dose in Grays received by 90% of the prostate volume) at day 30.
Mean baseline prostate volume (V1) was 37.4 ± 9.6 cc. A volume increase of >5% was seen in 51% between V1-V2 (mean = 2.5 cc, p < 0.01), in 42% between V2-V3 (mean = 1.9 cc, p < 0.01) and in 71% between V1-V3 (mean = 4.5 cc, p < 0.01). Pvol changes caused by insertion of the fixation needles were not statistically different than those caused by the implant itself (p = 0.23).
In multivariate linear regression analysis, baseline Pvol is predictive of Pvol changes between V2 and V1 and V3 and V1 but not between V3 and V2. The extent of prostate swelling had an influence on D90. An increase of 10% in prostate volume between V1 and V2 results in an increase of D90 at Day 30 by 11.7%. Baseline Pvol (V1) was the only predictor of the duration of urinary retention in both univariate and multivariate (p = 0.04) regression analysis.
A large part of intraoperative swelling occurs already after the insertion of the fixation needles. This early prostate swelling predicts for D90 but not for AUR.
Prostate; Permanent seed brachytherapy; Intra-operative edema
Permanent prostate brachytherapy is frequently performed worldwide, and many studies have demonstrated its favorable outcomes. Implant seeds used in this procedure contain a precise amount of radionuclide and are completely sealed. Because these seeds are not manufactured in Japan, they are expensive (6300 yen per seed) and therefore need careful management as a radioisotope. The proper implantation technique requires considerable procedure time, good dosimetric outcomes and simple radioactive isotope management. To evaluate the modified hybrid interactive technique based on these considerations, we assessed 313 patients who underwent hybrid interactive brachytherapy without additional external beam radiotherapy. We evaluated the duration of the procedure, dosimetric factors and the total number of excess seeds. The dosimetric results from computed tomography on Day 30 of follow-up were: 172 Gy (range 130–194 Gy) for pD90, 97.8% (83.5–100%) for pV100, 54.6% (27.5–82.4%) for pV150, 164 Gy (120–220 Gy) for uD90, 194 Gy (126–245 Gy) for uD30, 210 Gy (156–290 Gy) for uD5, 0.02 ml (0–1.2 ml) for rV100 and 0 ml (0–0.2 ml) for rV150. The number of excess seeds was determined by subtracting the number of implanted seeds from the expected number of seeds calculated from previously proposed nomograms. As per our method, nine excess seeds were used for two patients, whereas using the nomograms, the number of excess seeds was approximately eight per patient. Our modified hybrid interactive technique reduced the number of excess seeds while maintaining treatment quality.
prostate cancer; excess seeds; I-125; hybrid interactive brachytherapy
Post-implant dosimetric assessment is essential for optimal care of patients receiving prostate brachytherapy. In most institutions, post-implant computed tomography (CT) is performed in the supine position. This study aimed to assess variability in dosimetric parameters with postural changes during acquisition of post-implant CT scans.
Material and methods
In total, 85 consecutive patients were enrolled in this study. Fifty-three patients underwent seed implantation alone, and the remaining 32 received a combination of seed implantation and external beam radiotherapy. For post-implant analyses, CT scans were obtained in two patient positions, supine and prone. To evaluate differences in dosimetric parameters associated with postural change, the dosimetric data obtained in the supine position were defined as the standard.
The median prostate volume was 22.4 ml in the supine and 22.5 ml in the prone position (p = 0.51). The median prostate D90 was 120.1% in the supine and 120.3% in the prone position, not significantly different. The mean prostate V100 was 97.1% in the supine and 97.0% in the prone position, again not significantly different. Median rectal V100 in supine and prone positions were 0.42 ml and 0.33 ml, respectively (p < 0.01). Rectal D2cc was also significantly decreased in the prone as compared with the supine position (median, 59.1% vs. 63.6%; p < 0.01). A larger post-implant prostate volume was associated with decreased rectal doses in the prone position.
Though there were no significant differences among prostate D90 assessments according to postural changes, our results suggest that post-implant rectal doses decreased in the prone position.
prostate cancer; brachytherapy; post-implant; position; prone
The purpose of this study was to determine the risk factors for rectal bleeding after prostate brachytherapy. Between April 2005 and September 2009, 89 patients with T1c-2cN0M0 prostate cancer were treated with permanent I-125 seed implantation alone. The prostate prescription dose was 145 Gy, and the grade of rectal bleeding was scored according to the Common Terminology Criteria for Adverse Events version 4.0. Post-treatment planning was performed with fusion images of computerized tomography and magnetic resonance imaging 4–5 weeks after brachytherapy. Patient characteristics and dosimetric parameters were evaluated to determine risk factors for bleeding. The calculated parameters included the rectal volume in cubic centimeters that received >50–200% of the prescribed dose (RV50–200) and the minimal doses received by 1–30% of the rectal volume (RD1–30). The median follow-up time was 42 months (ranging 18–73 months). Grade 1 rectal bleeding occurred in 24 (27.0%) patients, but no Grade 2 or severe bleeding was observed. Usage of anticoagulants had a significant correlation with the occurrence of bleeding (P = 0.007). The RV100–150 and RD1–10 were significantly higher in patients with rectal bleeding than in those without bleeding. The RV100 was identified as a possible threshold value; the 3-year rectal bleeding rate in patients with an RV100 > 1.0 cm3 was 36%, whereas that with an RV100 ≤ 1.0 cm3 was 14% (P < 0.05). Although no Grade 2 morbidity developed in this study, the RV100 should be kept below 1.0 cm3, especially in additional dose-escalated brachytherapy.
prostate cancer; brachytherapy; rectal bleeding; dose-volume-histogram; anticoagulant
To evaluate the long term effectiveness of transrectal ultrasound (TRUS)-guided permanent radioactive I125 implantation of the prostate for organ confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy (EBRT) within a cooperative group setting.
Methods and Materials
Patients accrued to this study had histologically confirmed, locally confined, adenocarcinoma of the prostate clinical stage T1b, T1c, or T2a, no nodal or metastatic disease, prostate specific antigen (PSA) level of ≤ 10 ng/ml and a Gleason score of ≤ 6. All patients underwent TRUS-guided radioactive I125 seed implantation into the prostate. The prescribed dose was 145 Gy to the prostate planning target volume (PTV).
A total of 101 patients from 27 institutions were accrued to this protocol; by design no single institution accrued more than 8 patients. There were 94 eligible patients. The median follow up was 8.1 years (range 0.1 to 9.2 years). After 8 years, 8 patients had protocol-defined biochemical (PSA) failure (cumulative incidence 8.0%), 5 patients had local failure (cumulative incidence 5.5%), and 1 patient had distant failure (cumulative incidence 1.1%; this patient also had biochemical failure and non-prostate cancer related death). The 8-year overall survival (OS) rate was 88%. At last follow up, no patient died of prostate cancer or related toxicities. Three patients had maximum late toxicity of Grade 3 and all were genitourinary (GU). There were no Grade 4 or 5 toxicities observed.
The long term results of this clinical trial have demonstrated that this kind of trial can be successfully completed through the RTOG and that results in terms of biochemical failure and toxicity compare very favorably with other brachytherapy published series as well as surgical and external beam radiotherapy series. Additionally, the prospective, multi-centered design highlights the probably generalizability of the outcomes.
Prostate; brachytherapy; low dose rate (LDR)
To evaluate the outcomes of patients presenting with cancer at the base of the prostate after brachytherapy as monotherapy.
Material and methods
We retrospectively reviewed the medical records of all patients who had undergone transperineal ultrasound-guided implantation with 125I or 103Pd seeds as monotherapy between March 1998 and December 2006, at our institution. A minimum follow-up interval of 2 years was required for inclusion in our analysis. Dosimetry was assessed using computed tomography 30 days after the implant. Treatment failure was defined as the appearance of biopsy-proved tumor after seed implantation, radiographic evidence of metastases, receipt of salvage therapy, or elevation of the prostate-specific antigen level beyond the nadir value plus 2 ng/mL.
With a median follow-up interval of 89 months (range 25–128 months), all 52 of the identified patients had no evidence of disease progression or biochemical failure. The mean number of cores sampled at the prostate base was 2.84 (median 2); Gleason scores assigned at central review were 6-8 in all patients. Of the 30 patients (58%) for whom dosimetric data were available at day 30, the median V100 values of the right and left base were 92.0% and 93.5%, respectively, and the median D90 values of the right and left base were 148 Gy and 151 Gy, respectively.
Permanent prostate brachytherapy as monotherapy results in a high probability of disease-free survival for men with cancer at the base of the prostate.
prostate cancer; monotherapy; sector analysis
Background & Purpose
Rectal toxicity is less common after 125I seed implant brachytherapy for prostate cancer, and intraoperative rectal dose-volume constraints (the constraint) is still undetermined in pioneering studies. As our constraint failed to prevent grade 2 or 3 rectal bleeding (bled-pts) in 5.1% of patients, we retrospectively explored another constraint for the prevention of rectal bleeding.
Materials and methods
The study population consisted of 197 patients treated with the brachytherapy as monotherapy using real-time intraoperative transrectal ultrasound (US)-guided treatment at a prescribed dose of 145 Gy. Post-implant dosimetry was performed on Day 1 and Day 30 after implantation using computed tomography (CT) imaging. Rectal bleeding toxicity was classified by CTC-AE ver. 3.0 during a mean 29-month (range, 12-48 months) period after implantation. The differences in rV100s were compared among intraoperative, Day 1 and Day 30 dosimetry, and between that of patients with grade 2 or 3 rectal bleeding (the bled-pts) and of the others (the spared-pts). All patients were divided into groups based on provisional rV100s that were increased stepwise in 0.1-cc increments from 0 to 1.0 cc. The difference in the ratios of the bled-pts to the spared-pts was tested by chi-square tests, and their odds ratios were calculated (bled-OR). All statistical analyses were performed by t-tests.
The mean values of rV100us, rV100CT_1, and rV100CT_30 were 0.31 ± 0.43, 0.22 ± 0.36, and 0.59 ± 0.68 cc, respectively. These values temporarily decreased (p = 0.020) on Day 1 and increased (p = 0.000) on Day 30. There was no significant difference in rV100s between the bled-pts and spared-pts at any time of dosimetry. The maximum bled-OR was identified among patients with an rV100us value above 0.1 cc (p = 0.025; OR = 7.8; 95% CI, 1.4-145.8); an rV100CT_1 value above 0.3 cc (p = 0.014; OR = 16.2; 95% CI, 3.9-110.7), and an rV100CT_30 value above 0.5 cc (p = 0.019; OR = 6.3; 95% CI, 1.5-42.3).
By retrospective analysis exploring rV100 as intraoperative rectal dose-volume thresholds in 125I seed implant brachytherapy for prostate cancer, it is proved that rV100 should be less than 0.1 cc for preventing rectal bleeding.
prostate cancer; brachytherapy; dose-volume histogram
We investigated the usefulness of the fusion image created by transrectal ultrasonography (TRUS) and large-bore computed tomography (CT) for predicting pubic arch interference (PAI) during prostate seed brachytherapy. The TRUS volume study was performed in 21 patients, followed by large-bore computed tomography of patients in the lithotomy position. Then, we created TRUS-CT fusion images using a radiation planning treatment system. TRUS images in which the prostate outline was the largest were overlaid on CT images with the narrowest pubic arch. PAI was estimated in the right and left arch separately and classified to three grades: no PAI, PAI positive within 5 mm and PAI of >5 mm. If the estimated PAI was more than 5 mm on at least one side of the arch, we judged there to be a significant PAI. Brachytherapy was performed in 18 patients who were evaluated as not having significant PAI on TRUS. Intra-operative PAI was observed in one case, which was also detected with a fusion image. On the other hand, intra-operative PAI was not observed in one case that had been evaluated as having significant PAI with a fusion image. In the remaining three patients, TRUS suggested the presence of significant PAI, which was also confirmed by a fusion image. Intra-operative PAI could be predicted by TRUS-CT fusion imaging, even when it was undetectable by TRUS. Although improvement of the reproducibility of the patients’ position to avoid false-positive cases is warranted, TRUS-CT fusion imaging has the possibility that the uncertainty of TRUS can be supplemented.
prostate cancer; brachytherapy; seed implantation; pubic arch interference; fusion image
To evaluate in a multicenter setting the ability of centers to perform pre-implant permanent prostate brachytherapy planning, fulfilling dosimetric goals and constraints based on the Groupe de Curiethérapie-European Society for Radiotherapy and Oncology guidelines in the setting of implantation after prior prostate transurethral resection (TURP).
Material and methods
A reference transrectal ultrasound image set of the prostate gland from a patient who had undergone TURP was used. Contouring of the prostate, clinical target volume and organs at risk was performed by the coordinating center. Goals and constraints regarding the dosimetry were defined.
Seventeen of twenty-five centers invited to participate were able to import the Digital Imaging and Communications in Medicine-images into their planning computer and plan the implant using the defined guidelines. All centers were able to plan treatment, and achieve the recommended objectives and constraints. However, sector analysis has shown a risk of under-dosage in the anterior part of the prostate.
Correct pre-implantation planning with adherence to protocol guidelines and in compliance with defined dosimetric constraints seems feasible in a post-TURP setting, at least on a theoretical basis. A prospective study evaluating the outcome of prostate brachytherapy performed after TURP can therefore be undertaken with an expectation of a correct dosimetry in the multicenter setting.
brachytherapy; permanent seed implant; prostate cancer; transurethral resection; TURP
There is a 0.16% chance of a rectourethral fistula after prostate brachytherapy monotherapy using Palladium-103 or Iodine-125 implants. We present an unusual case report of a rectourethral fistula following brachyradiotherapy monotherapy for prostate adenocarcinoma. It was also associated with unusual management of the fistula.
A 58-year-old Caucasian man underwent brachyradiotherapy monotherapy as definitive treatment for verified intracapsular prostate adenocarcinoma receiving 56 Iodine-125 implants using a transrectal ultrasound-guided technique. The patient started to complain of severe perineal pain and mild rectal bleeding 15Â months after brachyradiotherapy. A biopsy of mucosa of his anterior rectal wall was performed. A moderate sized rectourethral fistula was confirmed 23Â months after implantation of Iodine-125 seeds. Laparoscopic sigmoidostomy and suprapubic cystostomy were then performed. Long-term cortisone applications in combination with 30 sessions of hyperbaric oxygen therapy, and antibacterial therapies were initiated due to necrotic infection. A gracilis muscle interposition to create a partition between the patient's rectum and urethra in conjunction with primary rectal repair but without urethral repair were performed 6 months later. The 3cm rectal defect was repaired via a 3cm-long horizontal perineal incision. The 1.5cm urethral defect just below the prostate was not repaired. The patient underwent an optic internal urethrotomy 3Â months later for a 1.5cm-long urethral stricture. Several planned preventive urethral buginages were performed to avoid urethral stricture recurrence. At 12Â months postoperatively, there were no signs of a fistula and cancer recurrence. He now has a normal voiding and anal continence.
Severe rectal pain, bleeding, and local anterior necrotic proctitis are predictors of a rectourethral fistula. Urinary and fecal diversion is the first-step operation. Gracilis muscle interposition in conjunction with primary rectal repair but without urethral reconstruction is one of the reconstructive surgery options for moderate 2cm to 3cm rectourethral fistulas. Internal urethrotomy is a procedure for postoperative urethral strictures of 1.5cm in length.
Brachytherapy; Gracilis interposition; Prostate cancer; Radiotherapy; Rectal repair; Rectourethral fistula
In prostate brachytherapy, a transrectal ultrasound (TRUS) will show the prostate boundary but not all the implanted seeds, while fluoroscopy will show all the seeds clearly but not the boundary. We propose an intensity-based registration between TRUS images and the implant reconstructed from uoroscopy as a means of achieving accurate intra-operative dosimetry. The TRUS images are first filtered and compounded, and then registered to the uoroscopy model via mutual information. A training phantom was implanted with 48 seeds and imaged. Various ultrasound filtering techniques were analyzed, and the best results were achieved with the Bayesian combination of adaptive thresholding, phase congruency, and compensation for the non-uniform ultrasound beam profile in the elevation and lateral directions. The average registration error between corresponding seeds relative to the ground truth was 0.78 mm. The effect of false positives and false negatives in ultrasound were investigated by masking true seeds in the uoroscopy volume or adding false seeds. The registration error remained below 1.01 mm when the false positive rate was 31%, and 0.96 mm when the false negative rate was 31%. This fully automated method delivers excellent registration accuracy and robustness in phantom studies, and promises to demonstrate clinically adequate performance on human data as well. Keywords: Prostate brachytherapy, Ultrasound, Fluoroscopy, Registration.
This study was performed to develop and evaluate a semi-automatic seed localization algorithm from magnetic resonance (MR) images for interstitial prostate brachytherapy. The computerized tomography (CT) and MR images (3 mm-slice thickness) of six patients who had received real-time MR imaging-guided interstitial prostate brachytherapy were obtained. An automatic seed localization method was performed on CT images to obtain seed coordinates, and an algorithm for seed localization from MR images of the prostate was developed and tested. The resultant seed distributions from MR images were then compared to CT-derived distribution by matching the same seeds and calculating percent volume receiving 100% of the prescribed dose and the extent of the volume in 3-dimensions. The semiautomatic seed localization method made it possible to extract more than 90% of the seeds with either less than 8% of noises or 3% of missing seeds. The mean volume difference obtained from CT and MR receiving 100% of the prescribed dose was less than 3%. The maximum extent of the volume receiving the prescribed dose were 0.3, 0.6, and 0.2 cm in x, y, and z directions, respectively. These results indicate that the algorithm is very useful in identifying seeds from MR image for post-implant dosimety.
Seed Localization; Prostate; Interstitial; Brachytherapy; Magnetic Resonance; Computed Tomography; 125I
The optimal protocol for 125I-transperineal prostatic brachytherapy (TPPB) in intermediate-risk prostate cancer (PCa) patients remains controversial. Data on the efficacy of combining androgen-deprivation therapy (ADT) with 125I-TPPB in this group remain limited and consequently the guidelines of the American Brachytherapy Society (ABS) provide no firm recommendations.
Seed and Hormone for Intermediate-risk Prostate Cancer (SHIP) 0804 is a phase III, multicenter, randomized, controlled study that will investigate the impact of adjuvant ADT following neoadjuvant ADT and 125I-TPPB. Prior to the end of March, 2011, a total of 420 patients with intermediate-risk, localized PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from 20 institutions, all of which have broad experience of 125I-TPPB. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will initially undergo 3-month ADT prior to 125I-TPPB. Those randomly assigned to adjuvant therapy will subsequently undergo 9 months of adjuvant ADT. All participants will be assessed at baseline and at the following intervals: every 3 months for the first 24 months following 125I-TPPB, every 6 months during the 24- to 60-month post-125I-TPPB interval, annually between 60 and 84 months post-125I-TPPB, and on the 10th anniversary of treatment.
The primary endpoint is biochemical progression-free survival (BPFS). Secondary endpoints are overall survival (OS), clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, acceptability (assessed using the international prostate symptom score [IPSS]), quality of life (QOL) evaluation, and adverse events. In the correlative study (SHIP36B), we also evaluate biopsy results at 36 months following treatment to examine the relationship between the results and the eventual recurrence after completion of radiotherapy.
These two multicenter trials (SHIP0804 & SHIP36B) are expected to provide crucial data regarding the efficacy, acceptability and safety of adjuvant ADT. SHIP36B will also provide important information about the prognostic implications of PSA levels in intermediate-risk PCa patients treated with 125I-TPPB.
NCT00664456, NCT00898326, JUSMH-BRI-GU05-01, JUSMH-TRIGU0709
Radical radiotherapy is one of the options for the management of prostate cancer. In external beam therapy, 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) are the options for delivery of increased radiation dose, as vital organs are very close to the prostate and a higher dose to these structures leads to an increased toxicity. In brachytherapy, low dose rate brachytherapy with permanent implant of radioactive seeds and high dose rate brachytherapy (HDR) with remote after loaders are available. A dosimetric analysis has been made on IMRT and HDR brachytherapy plans. Ten cases from each IMRT and HDR brachytherapy have been taken for the study. The analysis includes comparison of conformity and homogeneity indices, D100, D95, D90, D80, D50, D10 and D5 of the target. For the organs at risk (OAR), namely rectum and bladder, V100, V90 and V50 are compared. In HDR brachytherapy, the doses to 1 cc and 0.1 cc of urethra have also been studied. Since a very high dose surrounds the source, the 300% dose volumes in the target and within the catheters are also studied in two plans, to estimate the actual volume of target receiving dose over 300%. This study shows that the prescribed dose covers 93 and 92% of the target volume in IMRT and HDR brachytherapy respectively. HDR brachytherapy delivers a much lesser dose to OAR, compared to the IMRT. For rectum, the V50 in IMRT is 34.0cc whilst it is 7.5cc in HDR brachytherapy. With the graphic optimization tool in HDR brachytherapy planning, the dose to urethra could be kept within 120% of the target dose. Hence it is concluded that HDR brachytherapy may be the choice of treatment for cancer of prostate in the early stage.
Brachytherapy; conformity; intensity modulated radiotherapy; prostate
Prostate brachytherapy is a treatment for prostate cancer using radioactive seeds that are permanently implanted in the prostate. The treatment success depends on adequate coverage of the target gland with a therapeutic dose, while sparing the surrounding tissue. Since seed implantation is performed under transrectal ultrasound (TRUS) imaging, intraoperative localization of the seeds in ultrasound can provide physicians with dynamic dose assessment and plan modification. However, since all seeds cannot be seen in the ultrasound images, registration between ultrasound and fluoroscopy is a practical solution for intraoperative dosimetry. In this manuscript, we introduce a new image-based nonrigid registration method that obviates the need for manual seed segmentation in TRUS images and compensates for the prostate displacement and deformation due to TRUS probe pressure. First, we filter the ultrasound images for subsequent registration using thresholding and Gaussian blurring. Second, a computationally efficient point-to-volume similarity metric, an affine transformation and an evolutionary optimizer are used in the registration loop. A phantom study showed final registration errors of 0.84 ± 0.45 mm compared to ground truth. In a study on data from 10 patients, the registration algorithm showed overall seed-to-seed errors of 1.7 ± 1.0 mm and 1.5 ± 0.9 mm for rigid and nonrigid registration methods, respectively, performed in approximately 30 seconds per patient.
Prostate Brachytherapy; Registration; Fluoroscopy; Ultrasound
Periprostatic brachytherapy doses impact biochemical control. In this study, we evaluate extracapsular volumetric dosimetry following permanent prostate brachytherapy in patients entered in a multi-institutional community database.
Material and methods
In the database, 4547 patients underwent brachytherapy (3094 – 125I, 1437 – 103Pd and 16 – 131Cs). Using the originally determined prostate volume, a 5 mm, 3-dimensional peri-prostatic anulus was constructed around the prostate (except for a 2 mm posterior margin), and evaluated in its entirety and in 90° segments. Prostate dosimetric parameters consisted of a V100 and D90 while the annular dosimetry was reported as a V100.
The intraprostatic V100 and D90 for 103Pd, and 125I were statistically comparable when stratified by isotope and/or monotherapy vs. boost. The overall mean V100 for the periprostatic annulus was 62.8%. The mean V100 at the base (51.6%) was substantially less than the apex (73.5%) and midgland (65.9%). In addition, for all patients, the anterior V100 (45.7%) was less than the lateral (68.8%) and the posterior (75.0%). The geometric V100 annular differences were consistent when evaluated by isotope. Overall, the V100 was higher in the 125I cohort.
The optimal extracapsular brachytherapy dose and radial extent remains unknown, but will prove increasingly important with reductions and/or elimination of supplemental external beam radiation therapy. The large multi-institutional community database demonstrates periprostatic annular doses that are not as robust as those in selected high volume brachytherapy centers, and may be inadequate for optimal biochemical control following monotherapeutic brachytherapy, especially in higher risk patients.
brachytherapy; dosimetry; prostate cancer; treatment margins
To perform a dosimetric comparison between a pre-planned technique and a pre-plan based intraoperative technique in prostate cancer patients treated with I-125 permanent seed implantation.
Material and methods
Thirty patients were treated with I-125 permanent seed implantation using TRUS guidance. The first 15 of these patients (Arm A) were treated with a pre-planned technique using ultrasound images acquired prior to seed implantation. To evaluate the reproducibility of the prostate volume, ultrasound images were also acquired during the procedure in the operating room (OR). A surface registration was applied to determine the 6D offset between different image sets in arm A. The remaining 15 patients (Arm B) were planned by putting the pre-plan on the intraoperative ultrasound image and then re-optimizing the seed locations with minimal changes to the pre-plan needle locations. Post implant dosimetric analyses included comparisons of V100(prostate), D90(prostate) and V100(rectum).
In Arm A, the 6D offsets between the two image sets were θx=−1.4±4.3; θy=−1.7±2.6; θz=−0.5±2.6; X=0.5±1.8 mm; Y=−1.3±−3.5 mm; Z=−1.6±2.2 mm. These differences alone degraded V100 by 6.4% and D90 by 9.3% in the pre-plan, respectively. Comparing Arm A with Arm B, the pre-plan based intraoperative optimization of seed locations used in the plans for patients in Arm B improved the V100 and D90 in their post-implant studies by 4.0% and 5.7%, respectively. This was achieved without significantly increasing the rectal dose (V100(rectum)).
We have progressively moved prostate seed implantation from a pre-planned technique to a pre-plan based intraoperative technique. In addition to reserving the advantage of cost-effective seed ordering and efficient OR implantation, our intraoperative technique demonstrates increased accuracy and precision compared to the pre-planned technique.
pre-plan; intraoperative planning; seed implant; prostate cancer
The purpose of this study was to monitor patient pain score with transperineal prostatic gold seed implantation in the absence of conscious sedation.
All patients who were scheduled for image-guided external beam radiation (IGRT) and referred for gold seed fiducials were eligible to participate. Gold seed implants were performed by two radiation oncologists between December 2007 and April 2008. Patients received only local and deep anesthetic. No patients had prophylactic IV cannulation for the procedure. Three gold seeds were inserted transperineally into the prostate. A visual analogue scale from 0 to 10 was used to assess the pain at baseline, local and deep anesthetic infiltration, with each seed drop, and after the completion of the procedure.
A total of 30 patients were accrued to this study. The highest recorded increase in pain score was at the time point of deep local anesthesia, at which the mean pain score was 3.8. The mean pain scores at each seed drop were 0.8 (standard deviation [SD]=1.24), 1 (SD=1.26), and 0.5 (SD=0.90), respectively. All gold seed insertion procedures were well-tolerated, with no patients having significant pain post-procedure, and no significant procedural complications. There were only slight increases in dysuria, urinary frequency, constipation, urinary retention and flatulence in 7 patients – none of which required intervention.
Transperineal ultrasound-guided gold seed implantation without conscious sedation is well-tolerated and associated with a low complication rate. It is a convenient outpatient procedure obviating the need for resource intensive postoperative monitoring.
Combined transperineal prostate brachytherapy (TPPB) and external beam radiation (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter Phase II trial assessing combination of EBRT and TPPB boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented.
Intermediate-risk patients per MSKCC/NCCN criteria received six months of ADT, 45 Gy EBRT to the prostate and seminal vesicles, followed by TPPB with I125(100 Gy) or Pd103(90 Gy). Toxicity was graded using NCI CTC version 2 and RTOG late radiation morbidity scoring systems. Disease free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive PSA rises >1.0ng/ml after 18 months from treatment start), the 1997 ASTRO consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival.
61/63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. 6 deaths occurred, only one was attributed to prostate cancer. 6 year overall survival was 96.1%.
In a cooperative setting, combination of EBRT and TPPB boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer.
prostate; brachytherapy; radiation; cooperative group trial; hormonal therapy
Transrectal ultrasound (TRUS) has been widely used for guiding prostate implants, but not much for interstitial brachytherapy (IBT) of cervix cancer. The aim of our study is to report our experience with TRUS guided high dose rate (HDR) IBT in patients with carcinoma of uterine cervix.
During the year 2005-2006, 25 patients of cervical cancer not suitable for intracavitary radiotherapy (ICRT), were enrolled in this prospective study. We used B-K Medical USG machine (Falcon 2101) equipped with a TRUS probe (8658) having a transducer of 7.5 MHz for IBT. Post procedure, a CT scan was done for verification of needle position and treatment planning. Two weekly sessions of HDR IBT of 8-10 Gy each were given after pelvic external beam radiation therapy.
A total of 40 IBT procedures were performed in 25 patients. Average duration of implant procedure was 50 minutes. There was no uterine perforation in any of 11 patients in whom central tandem was used. CT scan did not show needle perforation of bladder/rectum in any of the patients. During perioperative period, only 1 procedure (2.5%) was associated with hematuria which stopped within 6 hours. Severe late toxicity was observed in 3 (12%) patients. Overall pelvic control rate was 64%.
Our experience suggests that TRUS is a practical and effective imaging device for guiding the IBT procedure of cervical cancer patients. It helps in accurate placements of needles thus avoiding the injury to normal pelvic structures.
Interstitial brachytherapy; Cervical neoplasms; Transrectal ultrasound
We have developed a tomosynthesis-based radioactive seed localization method for prostate brachytherapy. In contrast to the projection image-based matching approach, our method does not involve explicit segmentation of seeds and can recover hidden seeds. Modified distance map images are computed from a limited number of x-ray projection images, and are backprojected to reconstuct a 3-D volume of interest. Candidate seed locations are extracted from the reconstructed volume and false positive seeds are eliminated by solving an optimal geometry coverage problem. The simulation results indicate that the implanted seed locations can be estimated from three or four images depending on the number of seeds if the pose of a C-arm is known. The algorithm was validated using phantom and clinical patient data.
Tomosynthesis; prostate cancer; brachytherapy; modified distance map
Most patients, even some urologists, assume that prostate volume is the most important prognostic factor for lower urinary tract symptoms (LUTS). In some cases, however, prostatic inflammation is a more important factor in LUTS than is prostate volume. For this reason, comparison of the impact on LUTS of inflammation and prostate volume is an attractive issue.
Materials and Methods
From January 2000 to May 2009, 1,065 men aged between 47 and 91 years (who underwent transrectal ultrasound-guided prostate needle biopsy and transurethral prostatectomy) were retrospectively investigated. Components such as age, serum prostate-specific antigen (PSA) level, prostate volume, and the presence of prostatitis were investigated through independent-sample t-tests, chi-square tests, and univariate and multivariate analyses.
Chi-square tests between prostatitis, prostate volume, serum PSA, and severe LUTS showed that prostate volume (R=0.173; p=0.041) and prostatitis (R=0.148; p<0.001) were related to LUTS. In particular, for a prostate volume under 50 ml, prostatitis was a stronger risk factor than was prostate volume. Among the multivariate predictors, prostatitis (odds ratio [OR]: 1.945; p<0.001) and prostate volume (OR, 1.029; p<0.001) were found to be aggravating factors of LUTS.
For patients with prostate volume less than 50 ml, prostatitis was found to be a more vulnerable factor for LUTS. For those with prostate volume over 50 ml, on the other hand, the volume itself was a more significant risk factor than was prostatitis. In conclusion, the presence of prostatitis is one of the risk factors for LUTS with increased prostate volume.
Inflammation; Prostate; Prostatic hyperplasia