Physical derivation of nomograms in permanent prostate brachytherapy

PurposeTo demonstrate the physical origin of nomograms in permanent prostate brachytherapy, by using the correlation between fractional integral target dose (FITD) and target volume.Methods and MaterialsThe integral dose (ID) E delivered by unit activity is given by the integration of 4πr²D(r)/r²dr × 1.44T_1/2 using the point source model from AAPM TG43. If A is the total activity implanted, then total ID will be A × E. Integral target dose are obtained by multiplying the prostate volume V with mean dose D_mean by definition, assuming prostate gland has a unity density. The FITD the target receives is defined as FITD = D_meanV/AE by energy conservation in the target volume. From this equation, the total activity needed to achieve given dose for a target of volume V is obtained. Results are compared with existing nomograms for ¹²⁵I and ¹⁰³Pd, and available clinical data for ¹³¹Cs.ResultsAgreement within 10.0% for ¹²⁵I and ¹⁰³Pd compared with existing nomograms for gland sizes from 18 to 80 cc is observed. For ¹³¹Cs, the agreement is within 8.0% compared with available clinical data.ConclusionsIt is shown that the correlation between the FITD and target volume can be used to obtain the total activity needed to achieve prescribed dose. This correlation is inherent rather than empirical. It suggests that the correlation between fraction of energy deposition in target and target volume is the underlying physical origin for nomograms used in permanent prostate brachytherapy.     

MRI-based sector analysis enhances prostate palladium-103 brachytherapy quality assurance in a phase II prospective trial of men with intermediate-risk localized prostate cancer

PurposePalladium-103 (¹⁰³Pd) may be superior to other isotopes in brachytherapy for localized intermediate-risk prostate cancer because of its relatively short half-life, higher initial dose rate, and greater dose heterogeneity within the target volume; these properties also underscore the need for accurate target delineation and postimplant quality assurance. We assessed the use of prostate sector analysis based on MRI for quality assurance after ¹⁰³Pd monotherapy.Methods and MaterialsFifty men with intermediate-risk prostate cancer underwent ¹⁰³Pd monotherapy in a prospective phase II trial at MD Anderson Cancer Center. Dosimetric analyses on day 30 after the implant were done using both CT and fused CT/MRI scans. Dosimetric variables were assessed for the entire prostate and for each of three or six sectors. Volumes and dosimetric variables were compared with paired t tests.ResultsPostimplant dosimetric variables for the entire prostate were significantly different on CT vs. CT/MRI (p = 0.019 for V₁₀₀ and p < 0.01 for D₉₀). Prostate volumes were smaller on the CT/MRI scans (p < 0.00001). The base sector contributed the greatest difference, with doses based on CT/MRI lower than those based on CT (p < 0.01 for V₁₀₀ and D₉₀). To date, these lower base doses have not affected biochemical outcomes for patients with disease in prostate base biopsy samples.ConclusionsCT/MRI is more precise than CT for prostate volume delineation and dosimetric quality assessment and thus provides superior heterogeneity control assessment after ¹⁰³Pd monotherapy implants.     

Sector analysis of dosimetry of prostate cancer patients treated with low-dose-rate brachytherapy

PurposeBrachytherapy is an effective single treatment modality for low- and intermediate-risk prostate cancer. Here, we compare the radiation doses in different prostate sectors between the preimplant planning images and the postimplant dosimetry.Methods and MaterialsTwo hundred fifteen consecutive patients treated for prostate cancer by ¹²⁵I seed brachytherapy were assessed. Pretreatment plans using transrectal ultrasound images of the prostate were compared with the dose calculated on posttreatment MRI and CT scans obtained 1 month after seed implantation. Twelve sectors were generated by dividing the prostate base, midgland, and apex into four quadrants each. Pretreatment and posttreatment dosimetry were compared between the 12 different sectors of the prostate.ResultsAverage V₁₀₀ (percentage of prostate volume that receives 100% of the prescribed dose) in the preimplant planning images of the prostate was 99.9 ± 0.25% compared with postimplant V₁₀₀ of 94.8 ± 3.77% (p < 0.0001). Prostate V₁₀₀ in the postimplant dosimetry was >91% in all sectors, except the anterior base sector, in which it was 64.87 ± 20.96%. Average 1-month D₉₀ (the dose to 90% of the prostate volume) was 114.5 ± 10.55%. D₉₀ at 1 month compared with preimplant planning was lower in the prostate base and higher in the prostate apex (p < 0.001).ConclusionsOur results show that in ¹²⁵I seed brachytherapy, prostate base receives a lower dose and apex receives a higher dose compared with preimplant planned dose coverage.     

Long-term outcomes and prognostic factors in patients treated with intraoperatively planned prostate brachytherapy

PurposeEvaluate outcomes and prognostic factors in men with localized prostate cancer.Methods and MaterialsA total of 3760 patients have undergone prostate seed implantation at our institution. This review is of our initial 304 consecutive patients treated before January 30, 2001. A total of 124 patients were treated with ¹²⁵I implant monotherapy and 180 with ¹⁰³Pd implant combined with 45-Gy external beam radiation therapy.ResultsThe median followup was 10.3 years. A 10-year biochemical control for low risk (LR) was 98% , intermediate risk (IR) 94%, high risk (HR) 78%, and HR with one HR factor 88% (p < 0.001); cause-specific survival was 99%, 98%, and 84% for LR, IR, and HR, respectively (p < 0.001); No significant difference in outcome was seen for LR and IR patients (p > 0.3). On multivariate analysis, only pretreatment PSA, Gleason score, and T-stage were significant for biochemical control. Most biochemical failures occurred within 5 years (93%).ConclusionsWith a minimum followup of 10 years, results are excellent and do not differ for LR or IR prostate cancer patients. HR patients are a very heterogeneous group, and excellent results can still be achieved for HR patients with only one HR feature.     

Influence of Pro-Qura–generated Plans on Postimplant Dosimetric Quality: A Review of a Multi-Institutional Database

The influence of Pro-Qura–generated plans vs. community-generated plans on postprostate brachytherapy dosimetric quality was compared. In the Pro-Qura database, 2933 postplans were evaluated from 57 institutions. A total of 1803 plans were generated by Pro-Qura and 1130 by community institutions. Iodine-125 (¹²⁵I) plans outnumbered Palladium 103 (¹⁰³Pd) plans by a ratio of 3:1. Postimplant dosimetry was performed in a standardized fashion by overlapping the preimplant ultrasound and the postimplant computed tomography (CT). In this analysis, adequacy was defined as a V₁₀₀ > 80% and a D₉₀ of 90% to 140% for both isotopes along with a V₁₅₀ < 60% for ¹²⁵I and < 75% for ¹⁰³Pd. The mean postimplant V₁₀₀ and D₉₀ were 88.6% and 101.6% vs. 89.3% and 102.3% for Pro-Qura and community plans, respectively. When analyzed in terms of the first 8 sequence groups (10 patients/sequence group) for each institution, Pro-Qura planning resulted in less postimplant variability for V₁₀₀ (86.2–89.5%) and for D₉₀ (97.4–103.2%) while community-generated plans had greater V₁₀₀ (85.3–91.2%) and D₉₀ (95.9–105.2%) ranges. In terms of sequence groups, postimplant dosimetry was deemed “too cool” in 11% to 30% of cases and “too hot” in 12% to 27%. On average, no clinically significant postimplant dosimetric differences were discerned between Pro-Qura and community-based planning. However, substantially greater variability was identified in the community-based plan cohort. It is possible that the Pro-Qura plan and/or the routine postimplant dosimetric evaluation may have influenced dosimetric outcomes at community-based centers.     

Less-restrictive,patient-specific radiation safety precautions can be safely prescribed after permanent seed implantation

PurposeTo use radiation exposure rate measurements to determine patient-specific radiation safety instructions with the aim of reducing unnecessary precaution times and to evaluate potential doses to members of the public.Methods and MaterialsRadiation exposure rate measurements were obtained from 1279 patients with Stage T1-2 prostate cancer who underwent transperineal ¹²⁵I or ¹⁰³Pd seed implantation from January 1995 through July 2008. An algorithm was developed from these measurements to determine the required precaution times to maintain public effective doses below 50% of the limits for specific exposure situations.ResultsThe median air kerma rates at 30 cm from the anterior skin surface were 4.9 μGy/h (range: 0.1–31.5) for ¹²⁵I and 1.5 μGy/h (range: 0.02–14.9) for ¹⁰³Pd. The derived algorithms depended primarily on the half-life T_p, the measured exposure rate at 30 cm, and specific exposure situation factors. For the typical ¹⁰³Pd patient, no radiation safety precautions are required. For the typical ¹²⁵I patient, no precautions are required for coworkers, nonpregnant adults who do not sleep with the patient, or nonpregnant adults who sleep with the patient. Typical ¹²⁵I patients should only avoid sleeping in the “spoon” position (i.e., in contact) with pregnant adults and avoid holding a child for long periods of time in the lap for about 2 months.ConclusionsThe large number of cases available for this study permitted the development of an algorithm to simply determine patient-specific radiation safety instructions. The resulting precaution times are significantly less restrictive than those generally prescribed currently.     

Predicting biochemical tumor control after brachytherapy for clinically localized prostate cancer: The Memorial Sloan-Kettering Cancer Center experience

PurposeTo identify predictors of biochemical tumor control and present an updated prognostic nomogram for patients with clinically localized prostate cancer treated with brachytherapy.Methods and MaterialsOne thousand four hundred sixty-six patients with clinically localized prostate cancer were treated with brachytherapy alone or along with supplemental conformal radiotherapy. Nine hundred one patients (61%) were treated with Iodine-125 (¹²⁵I) monotherapy to a prescribed dose of 144 Gy, and 41 (4.5%) were treated with Palladium-103 (¹⁰³Pd) monotherapy to a prescribed dose of 125 Gy. In patients with higher risk features (n = 715), a combined modality approach was used, which comprised ¹²⁵I or ¹⁰³Pd seed implantation or Iridium-192 high–dose rate brachytherapy followed 1–2 months later by supplemental intensity-modulated image-guided radiotherapy to the prostate.ResultsThe 5-year prostate-specific antigen relapse-free survival (PSA-RFS) outcomes for favorable-, intermediate-, and high-risk patients were 98%, 95%, and 80%, respectively (p < 0.001). Multivariate Cox regression analysis identified Gleason score (p < 0.001) and pretreatment PSA (p = 0.04) as predictors for PSA tumor control. In this cohort of patients, the use of neoadjuvant and concurrent androgen deprivation therapy did not influence biochemical tumor control outcomes. In the subset of patients treated with ¹²⁵I monotherapy, D₉₀ > 140 Gy compared with lower doses was associated with improved PSA-RFS. A nomogram predicting PSA-RFS was developed based on these predictors and had a concordance index of 0.70.ConclusionsResults with brachytherapy for all treatment groups were excellent. D₉₀ higher than 140 Gy was associated with improved biochemical tumor control compared with lower doses. Androgen deprivation therapy use did not impact on tumor control outcomes in these patients.     

Clinical and dosimetric factors associated with acute rectal toxicity in patients treated with 131Cs brachytherapy for prostate cancer

Purpose¹³¹Cs has been recently introduced for use in prostate brachytherapy. We wished to identify clinical and dosimetric factors associated with acute bowel/rectal toxicity in patients treated with ¹³¹Cs.Methods and MaterialsPatients treated with ¹³¹Cs prostate brachytherapy at the University of Pittsburgh were asked to complete expanded prostate cancer index composite surveys preoperatively and at 2–4 weeks and 3 months postimplant. We identified patients who experienced acute and persistent acute bowel toxicity to determine if any factors could correlate with either situation.ResultsOne hundred six patients were treated with ¹³¹Cs from September 2006 to May 2008. Thirty-eight percent of patients met our criteria for patient-appreciated acute bowel symptoms. On multivariate analysis, the volume of rectum receiving 50% of the prescribed dose (R-V₅₀; 4.1 vs. 2.6 cc, p = 0.01), R-V₇₅ (1.3 vs. 0.62 cc, p = 0.01), the percentage of the prescribed dose received by 1 cc of the rectum (R-D-1cc; 75% vs. 64%, p = 0.02), and R-D-2cc (63% vs. 54%, p = 0.003) were found to be factors associated with a greater risk of severe acute bowel toxicity. At 3-month followup, 28% of patients had persistent acute bowel toxicity. On multivariate analysis, no factors were identified that correlated with persistent acute bowel toxicity.ConclusionsThis study identifies R-V₅₀, R-V₇₅, R-D-1cc, and R-D-2cc as factors associated with patient-appreciated acute rectal toxicity. We are performing dosimetric analysis to determine the optimal distance for the posterior needles from the prostate–rectal interface to decrease rectal dose while still maintaining adequate coverage of prostate.     

Prostate implant nomograms for the North American Scientific 103Pd seed.

Palladium-103-(103Pd) seed has been increasingly used in prostate implantation as either definitive or boost therapy because of its shorter half-life and higher initial dose rate. Because a growing number of radiation oncologists prefer real-time implantation in the operating room, it will be helpful if the total activity of the seeds can be determined based on the gland size before the patient is taken to the operating room. Based on our clinic data, nomograms have therefore been developed for one of the widely used 103Pd seeds, the MED3633 seed, which is produced by North American Scientific, Inc. (NASI). The total activities for implant volume ranging from 15 cc to 55 cc are provided for both seed "monotherapy" and seed boost.     

Dosimetric influence of seed spacers and end-weld thickness for permanent prostate brachytherapy

PurposeThe aim of this study was to analyze the dosimetric influence of conventional spacers and a cobalt chloride complex contrast (C4) agent, a novel marker for MRI that can also serve as a seed spacer, adjacent to ¹⁰³Pd, ¹²⁵I, and ¹³¹Cs sources for permanent prostate brachytherapy.Methods and MaterialsMonte Carlo methods for radiation transport were used to estimate the dosimetric influence of brachytherapy end-weld thicknesses and spacers near the three sources. Single-source assessments and volumetric conditions simulating prior patient treatments were computed. Volume–dose distributions were imported to a treatment planning system for dose–volume histogram analyses.ResultsSingle-source assessment revealed that brachytherapy spacers primarily attenuated the dose distribution along the source long axis. The magnitude of the attenuation at 1 cm on the long axis ranged from −10% to −5% for conventional spacers and approximately −2% for C4 spacers, with the largest attenuation for ¹⁰³Pd. Spacer perturbation of dose distributions was less than manufacturing tolerances for brachytherapy sources as gleaned by an analysis of end-weld thicknesses. Volumetric Monte Carlo assessment demonstrated that TG-43 techniques overestimated calculated doses by approximately 2%. Specific dose–volume histogram metrics for prostate implants were not perturbed by inclusion of conventional or C4 spacers in clinical models.ConclusionsDosimetric perturbations of single-seed dose distributions by brachytherapy spacers exceeded 10% along the source long axes adjacent to the spacers. However, no dosimetric impact on volumetric parameters was noted for brachytherapy spacers adjacent to ¹⁰³Pd, ¹²⁵I, or ¹³¹Cs sources in the context of permanent prostate brachytherapy implants.     

A comparison of preplan transrectal ultrasound with preplan-CT in assessing volume and number of seeds needed for real-time ultrasound-based intra-operative planning in prostate 125I seed implantation

PurposeIntra-operative (real-time) treatment planning has been adapted by many institutions for low–dose rate prostate brachytherapy. Although this allows dosimetric planning to be done during the procedure, preplan imaging to obtain a prostate volume is essential to identify the number of seeds to ensure adequate volume coverage. Currently, there is no consensus regarding the most appropriate imaging to obtain this information. We conducted a retrospective study to compare how volumes obtained from preplan CT (p-CT) scans or preplan transrectal ultrasound (p-TRUS) correlated with real-time ultrasound and postimplant CT volumes and the difference in accuracy of seed estimation between these techniques.Methods and MaterialsNinety-two patients underwent ¹²⁵I permanent seed implants at Thomas Jefferson University Hospital between February 2002 and August 2008. Fifty-one patients underwent p-TRUS before intra-operative planning and 41 patients were evaluated by p-CT.ResultsThe median difference in volume between preimplant imaging and the intra-operative planning ultrasound was 3.59 and 5.2 cc for patients who underwent p-TRUS and p-CT, respectively. p-TRUS volumes more closely correlated with real-time intra-operative volumes (R = 0.84 in all patients and R = 0.91 in hormone-naïve patients) vs. p-CT (R = 0.82). The median number of seeds wasted using p-CT was 18 vs. 7 using volumes derived from p-TRUS.ConclusionsThe number of seeds ordered could be more accurately obtained from p-TRUS volumes, and this translated into less seed wastage. Our findings indicate that p-TRUS is a more accurate and an economically superior alternative to p-CT imaging in the era of real-time ultrasound planning.     

Results of a dummy run of postimplant dosimetry between multi-institutional centers in prostate brachytherapy with <Superscript>125</Superscript>I seeds

Purpose  

To determine the reproducibility and precision of postimplant dosimetry following ¹²⁵I prostate brachytherapy (PB) and to evaluate the effects of learning and experience in CT-based postimplant dosimetry.