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.     

MRI-assisted radiosurgery: A quality assurance nomogram for palladium-103 and iodine-125 prostate brachytherapy

PurposeWe sought to develop an activity nomogram for magnetic resonance (MR)–planned permanent seed prostate brachytherapy to improve quality assurance through a secondary dosimetric check.Methods and MaterialsPatients undergoing MRI-assisted radiosurgery (MARS), whereby MRI is used for preoperative planning and postimplant dosimetry, were reviewed from May 2016 to September 2018. Planned activity (U) was fitted by MR-prostate volume (cc) via simple linear regression. Resulting monotherapy nomograms were compared with institutional nomograms from an ultrasound-planned cohort. Dosimetric coverage and external urinary sphincter (EUS) dose were also assessed for MR-planned patients.ResultsWe identified 183 patients treated with MARS: 146 patients received palladium-103 (¹⁰³Pd; 102 monotherapy and 44 boost), and 37 received iodine-125 (¹²⁵I) monotherapy. Median prostate volume was 28 cc (interquartile range: 22–35). Lines of best fit for implant activity were U = 4.344 × (vol) + 54.13 (R²: 95%) for ¹⁰³Pd monotherapy, U = 3.202 (vol) + 39.72 (R²: 96%) for ¹⁰³Pd boost and U = 0.684 (vol) + 13.38 (R²: 96%) for ¹²⁵I monotherapy. Compared with ultrasound, MR-planned nomograms had lower activity per volume (p < 0.05) for both ¹⁰³Pd monotherapy (∼6%) and ¹²⁵I monotherapy (∼11%), given a median size (30 cc) prostate. Across all MARS implants, postimplant dosimetry revealed a median V100% of 94% (interquartile range: 92–96%). Median EUS V125 was <1 cc for all patients, regardless of isotope.ConclusionsWe developed a quality assurance nomogram for MR-planned prostate brachytherapy. When compared with ultrasound-planned, MR-planned monotherapy resulted in a lower activity-to-volume ratio while maintaining dosimetric coverage, likely secondary to EUS-sparing and reduced planning target margins.     

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.     

The effects of edema on urethral dose following palladium-103 prostate brachytherapy.

The effects of edema on urethral dose after interstitial prostate brachytherapy with palladium-103 (103Pd) were studied. Fifty patients underwent a 90-Gy 103Pd implant followed by dosimetric computed tomography (CT). Twenty-one days later, a Foley catheter was reinserted and a dosimetric CT was repeated. The mean reduction in prostate volume between day 0 and day 21 was 16%. Median prostate D90 on day 0 was 89.7 Gy (range 59.5 to 127) and 99.5 Gy (range 62.5 to 130) on day 21. Median prostate V100 was 90% (range 63 to 98%) on day 0 and 96% (range 66 to 99%) on day 21. Median V150 was 61% (range 31 to 85%) on day 0 and 75% (range 39 to 93%) on day 21. Median urethral D50 was 107 Gy (range 57 to 201) on day 0 and 126 Gy (range 64 to 193) on day 21. Regression analysis demonstrated a significant correlation between the decrease in the prostate volume and the increased urethral D50 (r 0.58, p < 0.05). Acute urinary toxicity was 32% grade 0, 38% grade 1, and 30% grade 2. The median urethral D50 increased by a mean of 18% with a correlation coefficient of 0.58 (p < 0.05). Catheterization of the urethra was well tolerated and was of value in better characterizing urethral dose after 103Pd brachytherapy.     

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.     

Transperineal TRUS-guided prostate brachytherapy using loose seeds versus RAPIDStrand: a dosimetric analysis

PURPOSE: An analysis of the effect of stranded (125)I and loose (predominantly (103)Pd) sources on dosimetric outcomes of brachytherapy of the prostate. METHODS AND MATERIALS: Between September 1998 and December 2003, 473 patients were treated with brachytherapy for biopsy-proven carcinoma of the prostate. Of these, 337 (71%) procedures were performed using free seeds placed with a Mick applicator. Beginning in April 2002, a program of stranded (125)I sources (RAPIDStrand) was implemented; 136 (29%) patients were treated via this approach. Dosimetric variables were collected, as were events of urinary retention. RESULTS: Mean V100 values for the stranded (125)I approach were greater than those for free seeds (p < 0.0005), whether (125)I or (103)Pd (p < 0.005). Use of the strand was the most significant determinant of V100 of all variables examined. The stranded (125)I approach was also associated with higher mean D90 values and lower V150-urethral doses. CONCLUSIONS: Use of stranded (125)I was associated with superior dosimetric outcomes in this group of patients.     

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.     

Determination of task group 43 dosimetric parameters for CSM40 <Superscript>137</Superscript>Cs source for use in brachytherapy

The CSM40 ¹³⁷Cs source model is currently being used in clinical brachytherapy. According to the recommendations of task group No. 43 (TG-43) of the American Association of Physicists in Medicine, dosimetry parameters of brachytherapy sources should be determined by two independent investigators before their clinical use. The aim of this study was to determine the TG-43 dosimetry parameters for a medium-dose-rate CSM40 ¹³⁷Cs source. The determined dosimetric parameters included the air kerma strength, dose rate constant, radial dose function, and anisotropy function. To determine the source’s dosimetric parameters, the CSM40 source was stimulated by the Monte Carlo N-Particle MCNP code. The TG-43 parameters were compared with the data of Vijande et al. on this source. The results showed that the dosimetry parameters for this source had good agreement with the results of Vijande et al. The dosimetric parameters of the CSM40 source can be used in treatment-planning systems incorporating this source model. The data can also be used for the quality assurance of treatment-planning systems.     

Interobserver variability in rectum contouring in high-dose-rate brachytherapy for prostate cancer: A multi-institutional prospective analysis

PurposeThe aim of this study was to evaluate the interobserver variability (IOV) of rectum contouring, and its dosimetric consequences, for high-dose-rate brachytherapy in patients with prostate cancer across multiple institutions.Methods and MaterialsFive radiation oncologists contoured rectums in 10 patients on transperineal ultrasound image sets after establishing a delineation consensus. The D_0.1cc, D_1cc, and D_2cc rectum volume parameters were determined. The mean, standard deviation, and range of each dose–volume histogram parameter were evaluated for each patient. The IOV was determined using the coefficient of variation, and the dosimetric impacts on the total dose were analyzed by estimating the biologically equivalent dose (EQD_{2α/β = 3}).ResultsThe interobserver coefficients of variation (±standard deviation) for the reported D_0.1cc, D_1cc, and D_2cc were 5 ± 1.84%, 4 ± 1.26%, and 4 ± 1.33%, respectively. As for the impact on the total dose, the mean dose differences for D_0.1cc, D_1cc, and D_2cc were 10 Gy, 7.3 Gy, and 6.6 Gy, respectively.ConclusionsThe D_2cc is robust as evident by the low IOV (<5%). However, some variability ranges almost overlap with the clinical threshold level, which may present dosimetric and clinical complications. General rectal contouring guidelines for prostate high-dose-rate brachytherapy are desirable to reduce discrepancies in delineation.     

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.