Applicability and Dosimetric Impact of Ultrasound-Based Preplanning in High-Dose-Rate Brachytherapy of Prostate Cancer

BACKGROUND AND PURPOSE: Analyses of permanent brachytherapy seed implants of the prostate have demonstrated that the use of a preplan may lead to a considerable decrease of dosimetric implant quality. The authors aimed to determine whether the same drawbacks of preplanning also apply to high-dose-rate (HDR) brachytherapy. PATIENTS AND METHODS: 15 patients who underwent two separate HDR brachytherapy implants in addition to external-beam radiation therapy for advanced prostate cancer were analyzed. A pretherapeutic transrectal ultrasound was performed in all patients to generate a preplan for the first brachytherapy implant. For the second brachytherapy, a subset of patients were treated by preplans based on the ultrasound from the first brachytherapy implant. Preplans were compared with the respective postplans assessing the following parameters: coverage index, minimum target dose, homogeneity index, and dose exposure of organs at risk. The prostate geometries (volume, width, height, length) were compared as well. RESULTS: At the first brachytherapy, the matching between the preplan and actual implant geometry was sufficient in 47% of the patients, and the preplan could be applied. The dosimetric implant quality decreased considerably: the mean coverage differed by -0.11, the mean minimum target dose by -0.15, the mean homogeneity index by -0.09. The exposure of organs at risk was not substantially altered. At the second brachytherapy, all patients could be treated by the preplan; the differences between the implant quality parameters were less pronounced. The changes of prostate geometry between preplans and postplans were considerable, the differences in volume ranging from -8.0 to 13.8 cm(3) and in dimensions (width, height, length) from -1.1 to 1.0 cm. CONCLUSION: Preplanning in HDR brachytherapy of the prostate is associated with a substantial decrease of dosimetric implant quality, when the preplan is based on a pretherapeutic ultrasound. The implant quality is less impaired in subsequent implants of fractionated brachytherapy.     

Evaluation of post-plan dosimetry using TRUS and CT after transperineal prostate seed implant

The purpose of this study was to evaluate the variability in dosimetry due to the change in prostate volume for permanent transperineal brachytherapy seed implant. This research is the beginning of an in-house quality assessment program. Nineteen cases were retrospectively evaluated. A single physician defined prostate volumes in all cases. Group A consisted of 3 cases that were treated with external-beam radiation therapy (EBRT) to 4500 cGy, followed by a brachytherapy implant boost of 10,800 cGy. Group B included 16 cases that were implant only, prescribed to 14,400 cGy. Prostate images were acquired before seed implant using transrectal ultrasound (TRUS), immediately following seed implant using TRUS, and by computed tomography (CT) acquired several weeks postimplant. The prostate images were digitized into a commercial treatment planning system for planning purposes and dosimetric evaluation for the 3 procedures. Prostate volumes were calculated by the treatment planning system. Additional data collected included the percentage of prostate receiving the prescribed dose and dose to 90% and 80% of the prostate. The dose delivered to V₁₅₀ was also recorded. Overall, the postimplant ultrasound plan showed similar coverage to the ultrasound preplan, while the CT postplan revealed less than expected dosimetric coverage. The postplan CT results prompted us to evaluate our scheduling process, as well as prostate definition using TRUS and CT.     

Evaluation of HDR Interstitial Breast Implants Planned by Conventional and Optimized CT-Based Dosimetry Systems with Respect to Dose Homogeneity and Conformality

Background and Purpose: Recently, the use of brachytherapy for partial breast irradiation has increased significantly. The aim of this study was to make dosimetric comparisons between conventional (CONV) and CT-based optimized dosimetry systems applied to breast implants. Patients and Methods: 17 patients treated with high-dose-rate (HDR) interstitial brachytherapy were selected for the study. Two patients had two-plane and 15 three-plane implants. Treatment planning was based on conventional two isocentric radiographs and dose point optimization (CONV). For each patient postimplant CT scans were taken, and the target volume (lumpectomy cavity with 1 cm margin) was outlined in all axial slices. The treatment planning was repeated using CT images. The dose distributions were analyzed by dose-volume histograms. To quantify the dose distributions, volume (V90, V100, V150, V200) and dose (D90, D_min, mean central dose [MCD]) parameters, along with the dose nonuniformity ratio (DNR), dose homogeneity index (DHI), external volume index (EI) and conformal index (COIN) were used. For each implant, three more virtual treatment plans were created using the Paris dosimetry system (PDS), geometrically optimized system (GOS) and conformal system (CONF). Dose and volume parameters were calculated and compared. Results: The median number of catheters amounted to ten (range: 6 to 13) and the average volume of planning target volume to 63.4 cm³ (range: 17.7–122 cm³). The mean target coverage was 70%, 61%, 57% and 87%; the D90 72%, 64%, 60% and 94%; the DNR 0.35, 0.25, 0.25 and 0.55; the EI 0.62, 0.54, 0.08 and 0.15; the COIN 0.40, 0.34, 0.50 and 0.74 for the CONV, PDS, GOS and CONF systems, respectively. Conclusion: With CT-based optimized dose planning the target coverage can be significantly increased compared to the conventional dosimetry systems, but the target dose distribution will be more inhomogeneous. To improve the quality of brachytherapy implants, the image-based three-dimensional information should be used not only for dose plan evaluation, but also previously, for planning the geometry of the catheter positions and performing the insertions.     

Improved survival for patients with prostate cancer receiving high-dose-rate brachytherapy boost to EBRT compared with EBRT alone

PurposeHigh-dose-rate (HDR) brachytherapy boost is a treatment of intermediate- to high-risk prostate cancer, but long-term clinical outcome data are sparse. We report long-term survival and toxicity data in a cohort of patients treated in a single institution.MethodsBetween 1998 and 2004, 654 patients with localized prostate cancer received either 3-dimensional conformal radiotherapy (median 46 Gy) with an HDR (median 18 Gy in three fractions) boost (“3-D conformal radiotherapy [3DCRT] + HDR”; 215 patients) or 3DCRT alone (“3DCRT”; median 70 Gy; 439 patients) with curative intent. Men with National Comprehensive Cancer Network intermediate risk were offered neoadjuvant androgen deprivation and with high risk were also offered adjuvant androgen deprivation. Data collection included patient-reported outcome measures.ResultsThe 3DCRT + HDR group was older (72.3 vs. 68.9 yrs), had higher presenting PSAs (iPSA) (15.66 and 12.57 ng/mL, respectively), higher proportion of Gleason scores >7 (15.3% vs. 12.4%), and higher proportions of extracapsular disease (29.3% vs. 25.5%). 3DCRT + HDR men had lower proportions of low-risk patients (3.3% vs. 19.4%) and higher proportions of high-risk patients (50.7% vs. 37.4%) than the 3DCRT group. The 5-, 10-, and 15-year overall survival was superior at 92%, 81%, and 67%, respectively, for the 3DCRT + HDR group, compared with 88%, 71%, and 53%, respectively, in the 3DCRT group (p < 0.001). The 5-, 10-, and 15-year cause specific survival also favored the HDR boost group with survival of 96%, 93%, and 87% (3DCRT + HDR) and 95% 88% and 79% (3DCRT), respectively (p < 0.037).ConclusionsHDR brachytherapy boost in conjunction with 3DCRT offered superior overall survival and cause-specific survival in our patient population.     

Accelerated partial breast irradiation: a dosimetric comparison of three different techniques

PURPOSE: We report the first single-institutional dosimetric comparison of patients treated with three forms of accelerated partial breast irradiation: interstitial HDR brachytherapy, the MammoSite balloon apparatus, and 3D conformal external beam quadrant irradiation (3D-CRT). METHODS: A retrospective dosimetric comparison of interstitial HDR brachytherapy, MammoSite balloon brachytherapy, and 3D-CRT was performed. Thirty patients including 10 from each treatment technique were included for a dosimetric comparison of the dose received by the ipsilateral breast, PTV, heart, and ipsilateral lung. Interstitial patients were treated with 4 Gy in 8 fractions to 32 Gy, and the MammoSite patients were treated with 3.4 Gy in 10 fractions to 34 Gy. 3D-CRT patients were treated with 3.85 Gy in 10 fractions to 38.5 Gy using multiple isocentric beams. The CT images from simulation or implant evaluation were transferred into our 3D treatment planning software. The lumpectomy cavities were outlined for every patient, except the MammoSite patients, where the cavity was defined by the balloon edge. The PTV was constructed as a uniform expansion of 1.5 cm for all interstitial HDR patients, 1.0 cm for the MammoSite patients, and a 1.0 cm expansion in addition to the CTV expansion of 1.0 cm (n=2), and 1.5 cm (n=8) for the 3D-CRT patients. The CTV expansion for 3D-CRT and the PTV expansion for the brachytherapy patients were limited to the chest wall and skin. Normal structures including both ipsilateral lung and breast and heart for left-sided lesions were outlined. The lumpectomy cavity was subtracted from the PTV and normal breast tissue for evaluation. To evaluate dose to the ipsilateral breast and lung, PTV, and heart, a dose-volume histogram (DVH) analysis was performed. All histograms were normalized to the volume of the structure (i.e., expressed as percent volume). RESULTS: The average percentage of the breast receiving 100% and 50% of the prescribed dose (PD) was higher in the 3D-CRT group (24% and 48%, respectively) compared with the MammoSite (5% and 18%, respectively) and interstitial patients (10% and 26%, respectively). Improved coverage of the PTV was noted in the 3D-CRT plans compared with the MammoSite and interstitial HDR plans. With the interstitial HDR technique, 58% of the PTV received 100% of the PD compared with 76% with MammoSite and 100% with 3D-CRT techniques. The percentage of the PTV receiving 90% of the PD was 68%, 91%, and 100% for the interstitial HDR, MammoSite, and 3D-CRT patients, respectively. The ipsilateral lung V20 was slightly higher for 3D-CRT at 5% compared with 0% for both brachytherapy techniques. CONCLUSION: In those treated with 3D-CRT, coverage of the PTV was better with 3D-CRT but varied with the definition used. At the coverage at 90% of the PD, no difference was observed between 3D-CRT and MammoSite (which were both better than interstitial). 3D-CRT resulted in better coverage of the PTV compared with MammoSite or interstitial brachytherapy techniques. Better PTV coverage with 3D-CRT came at the cost of a higher integral dose to the remaining normal breast. Dosimetrically, the best partial breast irradiation technique appears to depend on the clinical situation. Of the brachytherapy techniques, MammoSite appears to be superior in PTV coverage. When comparing MammoSite vs. 3D-CRT PTV coverage at 90% of the PD, the difference was not significantly different.     

3-D Conformal HDR Brachytherapy as Monotherapy for Localized Prostate Cancer

PURPOSE: Pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose- rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning. PATIENTS AND METHODS: Between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) < or = 10 ng/ml, Gleason score < or = 7 and clinical stage < or = T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT((R)) was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (D(ref)) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D(90), D(10) urethra, and D(10) rectum. Acute toxicity was evaluated using the CTC (Common Toxicity Criteria) scales. RESULTS: Median D(90) was 106% of D(ref) (range: 93-115%), median D(10) urethra 159% of D(ref) (range: 127-192%), and median D(10) rectum 55% of D(ref) (range: 35-68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred. CONCLUSION: 3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.     

Assessment of HDR brachytherapy-replicating prostate radiotherapy planning for tomotherapy,cyberknife and VMAT

A dosimetric study was undertaken to assess the ability of Cyberknife (CK), Volumetric Modulated Arc Therapy (VMAT), and TomoTherapy (Tomo) to generate treatment plans that mimic the dosimetry of high dose-rate brachytherapy (HDR BT) for prostate cancer. The project aimed to assess the potential of using stereotactic body radiotherapy (SBRT) for boost treatment of high-risk prostate cancer patients where HDR BT in combination with conformal external beam radiotherapy (EBRT) is the standard of care. The datasets of 6 prostate patients previously treated with HDR BT were collated. VMAT, CK, and TomoTherapy treatment plans were generated for each dataset using the target and organ-at-risk structures as defined by the Radiation Oncologist during the HDR BT treatment process. The HDR BT plan isodoses were also converted into planning structures to assist the other modalities to achieve a HDR BT-like dose distribution. CK plans were created using both the iris collimator (IC) and a multileaf collimator (MLC). Comparison of the techniques was made based on dose-volume indices. Each plan was created at centres experienced using the respective treatment planning systems (TPS).Planning target volume (PTV V100%), i.e., the volume of the planning target volume (PTV) receiving 100% of the relative dose, in VMAT and TomoTherapy SBRT plans was higher than HDR BT plans. PTV V150% and V200%, i.e., volume of the PTV receiving 150% and 200% of the relative dose, were approached on all the CK MLC and TomoTherapy SBRT plans. However, it is not presently achievable for “virtual brachytherapy” SBRT to replicate the same high intraprostatic doses as HDR BT while meeting the constraints on the organs-at-risk (OARs). Half of the CK IC plans achieved PTV V150% but this was at the expense of high rectal dose. TomoTherapy and CK MLC plans achieved PTV V150% and V200% but the bladder dose was higher compared to CK IC plans. VMAT exhibited excellent PTV coverage based on V100 and OAR sparing, but without any ability to achieve the high intra-prostatic doses of HDR (V150% and V200%). SBRT techniques can be used to deliver hypofractionated radiotherapy to the PTV V100%. Based on the comparison of “physical” dose distributions, SBRT cannot presently achieve the same high intraprostatic doses as HDR BT while respecting the OAR constraints. SBRT still remains an attractive treatment option for delivering hypofractionated treatments for prostate cancer compared to HDR BT, in particular as it is less invasive and less resource intensive. Long-term outcomes of clinical trials comparing HDR BT and SBRT “prostate boosts” may show whether the high intraprostatic doses are clinically significant and correlate with outcomes.     

High-dose-rate brachytherapy in combination with conformal external beam radiotherapy in the treatment of prostate cancer

PurposeTo report long-term outcomes for treatment of prostate cancer using dose escalation with high-dose-rate (HDR) brachytherapy and 3-dimensional conformal external beam radiotherapy (3DCRT), and compare them with outcomes for treatment of prostate cancer with 3DCRT alone at the same institution.Methods and MaterialsFrom 1998 to 2003, 587 patients were treated for clinically localized prostate cancer. Patients received either 3DCRT (median, 46 Gy) with a single HDR brachytherapy implant (196 patients) delivering a fractionated dose of 18 Gy (combined group) or 3DCRT (median, 70 Gy; 387 patients; “3DCRT alone”). There were 41.9% patients with intermediate-risk and 42.6% with high-risk disease. In all, 441 patients (75.1%) received neoadjuvant and 116 patients (19.8%) received adjuvant androgen deprivation therapy. The American Society of Therapeutic Radiology and Oncology Phoenix definition for biochemical failure was used.ResultsThe median followup was 5.5 years. The 5- and 7-year biochemical control (BC) rates were 82.5% and 80.3%, respectively, for the combined group and 81.3% and 71%, respectively, for 3DCRT alone; for overall survival, they were 91.9% and 89.5% vs. 88.7% and 86.2%, respectively, whereas for cause-specific survival, they were 96.9% and 96.1% vs. 97.6% and 96.2%, respectively. Cox proportional hazard regression analysis for BC revealed that low Gleason grade, HDR brachytherapy combined with 3DCRT, and adjuvant androgen deprivation therapy were significant in predicting BC. Radiation Therapy Oncology Group Grade 3 late urinary and rectal morbidity rates were 7.1% and 0%, respectively. No Grade ≥4 reactions were detected.ConclusionsHDR brachytherapy combined with 3DCRT was associated with improved BC and minimal toxicity in patients with unfavorable prostate cancer compared with conventional 3DCRT.     

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.     

Influence of high-definition multileaf collimator for three-dimensional conformal radiotherapy and intensity-modulated radiotherapy of prostate cancer

The focus of this work is to evaluate the dosimetric impact of treatment planning for three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) of prostate cancer using Varian/BrainLAB 120-leaf high-definition multileaf collimator (HD120 MLC) with 2.5 mm leaf width and Varian 120-leaf millennium multileaf collimator (M120 MLC) with 5 mm leaf width. We measured the leaf transmission and dosimetric leaf gap (DLG) of two multileaf collimator (MLC) systems using Farmer ionization chamber. The dosimetric impact of treatment planning for 3DCRT and IMRT of prostate cancer for ten clinical cases using two MLC systems was evaluated quantitatively. 3DCRT was divided to 3DCRT(middle) as fitting at middle of leaf tip and 3DCRT(outside) as fitting at outside of leaf tip. The leaf transmission factor and DLG of HD120 MLC for 6 and 10 MV X-ray decreased by 0.2% and 1 mm, respectively, compared to M120 MLC. The mean conformity index of PTV of treatment planning for prostate 3DCRT(middle), 3DCRT(outside) , and IMRT decreased by 0.9%, 6.6%, and 0.9% and the mean homogeneity index increased 2.3%, 13.0%, and 4.2%, respectively. The mean V20, V40, and V65 decreased by 2.4%, 6.6%, and 4.5% for bladder and 3.3%, 6.1%, and 5.9% for rectum, respectively. The results of this work demonstrated that the dose conformity of PTV improved and the dose of bladder and rectum decreased for 3DCRT and IMRT of prostate cancer using HD120 MLC compared to M120 MLC, because of reduction of leaf width, leaf transmission, and rounded leaf end transmission.     

Combined modality treatment with high-dose-rate brachytherapy boost for locally advanced prostate cancer

PURPOSE: This is a retrospective review of our experience using high-dose-rate (HDR) brachytherapy boost for prostate cancer. METHODS AND MATERIALS: During the study period, we recommended external beam radiotherapy (45 Gy) and HDR boost (18 Gy in three fractions) combined with hormonal therapy (HT) for 2 months before and during radiotherapy to patients with at least one of the following risk features: pretreatment prostate-specific antigen>10, Gleason score (GS)>or=7, and clinical T3 disease. Additional HT for 2 years after radiotherapy was recommended for patients with GS>7. To patients whose risk of positive nodes exceeded 15%, we recommended whole pelvic radiotherapy. We administered HDR via single implant, and all fractions were given within 24h. RESULTS: This report is based on our initial 64 patients treated with HDR boost. The median follow-up was 50 months (range 25-68 months). The 4-year estimates of overall and disease-free survival were 98% and 92%, respectively. One patient experienced late grade 4 gastrointestinal toxicity. CONCLUSIONS: HDR brachytherapy is an effective means of delivering conformal prostate radiotherapy, and may be used with whole pelvic radiotherapy and HT.     

Comparison of high-dose rate prostate brachytherapy dose distributions with iridium-192, ytterbium-169, and thulium-170 sources

Purpose

Recent studies have identified that among different available radionuclides, the dose characteristics and shielding properties of ytterbium-169 (¹⁶⁹Yb) and thulium-170 (¹⁷⁰Tm) may suit high-dose rate (HDR) brachytherapy needs. The purpose of this work was to compare clinically optimized dose distributions using proposed ¹⁶⁹Yb and ¹⁷⁰Tm HDR sources with the clinical dose distribution from a standard microSelectron V2 HDR iridium-192 (¹⁹²Ir) brachytherapy source (Nucletron B.V., Veenendaal, The Netherlands).

Methods and materials

CT-based treatment plans of 10 patients having prostate volumes ranging from 17 to 92 cm³ were studied retrospectively. Clinical treatment of these patients involved 16 catheters and a microSelectron V2 HDR ¹⁹²Ir source. All dose plans were generated with inverse planning simulated annealing optimization algorithm. Dose objectives used for the ¹⁹²Ir radionuclide source were used for the other two radionuclides. The dose objective parameters were adjusted to obtain the same clinical target (prostate) volume coverage as the original ¹⁹²Ir radionuclide plan. A complete set of dosimetric indices was used to compare the plans from different radionuclides. A pairwise statistical analysis was also performed.

Results and conclusions

All the dose distributions optimized with specific ¹⁹²Ir, ¹⁶⁹Yb, and ¹⁷⁰Tm sources satisfied the standard clinical criteria for HDR prostate implants, such as those for the Radiation Therapy Oncology Group clinical trial 0321, for combined HDR and external beam treatment for prostate adenocarcinoma. For equivalent clinical target volume dose coverage, the specific ¹⁶⁹Yb and ¹⁷⁰Tm sources resulted in a statistically significant dose reduction to organs at risk compared with microSelectron V2 HDR ¹⁹²Ir source. This study indicates that a ¹⁷⁰Tm or ¹⁶⁹Yb radionuclide source may be an alternative to the ¹⁹²Ir radionuclide sources in HDR brachytherapy.