Prediction of seed migration after transperineal interstitial prostate brachytherapy with I-125 free seeds

PurposeThe present study was undertaken to determine the incidence and predictors of seed migration after transperineal interstitial prostate brachytherapy using I-125 free seeds.Methods and MaterialsBetween September 2004 and November 2007, 158 patients who underwent transperineal interstitial prostate brachytherapy as monotherapy for clinical T1/T2 carcinoma of the prostate gland were reviewed. Implants had been performed with standard techniques. All 158 patients underwent followup radiographs (orthogonal chest radiographs, a kidney–ureter–bladder radiograph, and a posteroanterior pelvic radiograph) to assess the presence of seed migration at 3 months after transperineal interstitial prostate brachytherapy. Patient characteristics and treatment status were recorded. Univariate and multivariate analyses were performed to identify predictors of seed migration.ResultsSeed migration occurred in 35 of 158 patients (22.2%). Univariate analyses revealed that preoperative prostate volume estimated by transrectal ultrasound, the number of needles, the number of seeds implanted, and the presence or absence of pubic arch interference (PAI) were significantly associated with seed migration. These results indicated that larger prostate glands were more likely to have seed migration. However, the absolute difference in prostate size was not overly impressive (22.4 vs. 26.3 cm³). Multivariate analysis revealed that the number of seeds implanted and the presence or absence of PAI were significant predictors of seed migration.ConclusionThe number of seeds implanted and the presence or absence of PAI provide the most predictive information on seed migration.     

Radioactive seed migration after transperineal interstitial prostate brachytherapy and associated development of small-cell lung cancer

PurposeWe report a case of lung carcinoma developing in the location of a migrated prostate brachytherapy seed.Methods and MaterialsA 57-year-old male nonsmoker was originally diagnosed with prostate adenocarcinoma Group IIB in October 1999. Treatment was completed at an outside local hospital and consisted of hormone suppression, pelvic external beam radiation, and transperineal interstitial permanent prostate brachytherapy with loose iodine-125 seeds.ResultsThe treatment was unremarkable for any complications, and immediate postimplant evaluation did not reveal any loose seeds. The patient remained clinically without evidence of disease and was asymptomatic until an isolated episode of hematuria in December 2009. Radiographic evaluation noted an incidental right lower lobe lung mass with a 4-mm hyperdensity slightly off-center. Biopsy confirmed Stage IB limited-stage small-cell lung cancer, and he underwent thoracic radiation with concurrent systemic chemotherapy. The mass remained mildly avid on a positron emission tomographic scan after treatment, and he underwent surgical evaluation with final pathology demonstrating no residual tumor but a metal rod-like implant consistent with a migrated radioactive brachytherapy seed.ConclusionsTo our knowledge, this is the first case of a long-term adverse sequela seen in the location of a migrated brachytherapy seed. Although reported incidence of pulmonary seed emboli remains low with little measurable consequence on pulmonary function, we must appreciate that a theoretical risk for secondary malignancy remains not only locally within the periprostatic region but also at any site of seed migration.     

A dosimetric analysis of unstranded seeds versus customized stranded seeds in transperineal interstitial permanent prostate seed brachytherapy

PURPOSE: This study aimed to retrospectively analyze the dosimetric and toxicity results from 272 patients with localized prostate cancer treated consecutively using loose or stranded radioactive seeds by transrectal ultrasound-guided transperineal permanent prostate seed brachytherapy. METHODS AND MATERIALS: Two hundred seventy-two patients with localized prostate cancer treated between February 2002 and June 2004 were analyzed. All patients were treated with radioactive iodine-125 or palladium-103 using unstranded or loose seeds (USS) (159 patients) or customized stranded seeds (CSS) at variable spacing (5-50 mm) (113 patients) (Vari-Strand; BrachySciences, Oxford, CT). A single experienced brachytherapist performed all implants. RESULTS: There was a slight improvement in the dosimetric parameter D90 between the CSS (101.9%) and USS (99.3%) groups (p = 0.041). However, overall implant quality based on Radiation Therapy Oncology Group (RTOG) guidelines was similar between both groups. CONCLUSIONS: We conclude that the D90 value calculated for CSS is statistically improved when compared to the USS cohort, but without a clinically significant difference. There was no difference in the toxicity scores in either group. Overall quality between groups is comparable in our institution.     

Relationship between Day 0 dosimetric parameters and biochemical relapse-free survival in patients treated with transperineal permanent prostate interstitial brachytherapy with 125I seeds

ObjectivesTo determine the relationship between dosimetric parameters obtained on postimplantation Day 0 and biochemical relapse-free survival (bRFS) in patients treated with ¹²⁵I transperineal interstitial permanent prostate brachytherapy (TIPPB).MethodsTwo-hundred twenty men with low-risk (n = 155, 70.4%), low-volume intermediate-risk (n = 63, 28.7%), or high-risk (n = 2, 0.9%) prostate cancer were treated with TIPPB between December 2000 and June 2006. Seventy-four (33.6%) patients received short-term (3–6 months) androgen suppression therapy before TIPPB. The median followup for patients free of biochemical failure was of 37.9 months (range, 24.0–84.5 months).ResultsThe receiver operating characteristic (ROC) analysis established a best-fit cutoff value for the quantifiers D₉₀ and V₁₀₀ of 147 Gy and 92%, respectively. The Kaplan–Meier analysis of bRFS at the cutoff value of D₉₀ = 147 Gy using the ASTRO, nadir + 2, and combined (ASTRO and nadir + 2) definitions showed a trend toward statistical significance for the ASTRO (p = 0.076) and nadir + 2 (p = 0.064) definitions and a statistically significant correlation for the combined definition (p = 0.033). The corresponding 7-year bRFS for the D₉₀ >147 Gy and D₉₀ ≤147 Gy subsets using the ASTRO, nadir + 2, and combined definitions were 96.5% vs. 89.7% (ASTRO, p = 0.076); 93.7% vs. 70.5% (nadir + 2, p = 0.064); and 94.4 vs. 75.5% (combined, p = 0.033). The V₁₀₀ (%) cutoff value of 92% predicted by the ROC analysis was not significant. Among other cutoff values, only D₉₀ = 140 Gy (p = 0.050) and D₉₀ = 160 Gy (p = 0.098) showed a trend toward statistical significance when the nadir + 2 and the ASTRO definitions were used. The rest of dosimetric, tumor, and patient parameters did not show statistical correlation with bRFS in the Kaplan–Meier analysis.ConclusionsThe cutoff value of D₉₀ = 147 Gy obtained on postimplantation Day 0 showed a trend toward significant correlation with bRFS when the standard ASTRO and nadir + 2 definitions were used and a weak but statistically significant correlation with bRFS as per the nonstandard combined definition in a series of patients with predominantly low-risk disease (70.4%) treated at high radiation doses (median D₉₀ = 152.9 Gy, median V₁₀₀ = 92.5%).     

Changes of edema associated with I-125 prostate brachytherapy

We have been performing TRUS-guided transperineal prostate brachytherapy with I-125 for prostate-confined adenocarcinoma since October 2003. We examined prostate volume using CT scanning on Day 1, Day 15, and Day 30 in the initial 15 patients, and investigated time-dependent changes of edema associated with I-125 prostate brachytherapy. Prostate volume had increased to 173% of the average on the first day after implantation. Improvements in the swelling of the prostate showed decreases in 30% in the first 2 weeks (Days 1-15) and 12% in the second 2 weeks (Days 15-30). V100 and D 90% showed statistically significant increases of 5.5% and 8.4% in the first 2 weeks after implantation and 2.3% and 5.2% in the second 2 weeks (Days 15-30). We considered one month a suitable time at which to calculate post-planning because V100 and D 90% changed little statistically.     

Radiation protection and dosimetry issues for patients with prostate cancer after I-125 low-dose-rate brachytherapy permanent implant

PurposeThe aim of this work was to analyze the exposure rates measured in the proximity of patients who underwent prostate low-dose-rate brachytherapy with I-125 implant. Effective doses to relatives and to population were computed to estimate the time to reach radioprotection dose constraints.Methods and MaterialsMeasurements were obtained from 180 patients, whereas the body mass index was calculated and reported for 77 patients. The day after the implant, $\dot{K}$ measurements were conducted at various skin distances and positions and converted to effective doses. A theoretical model was developed to estimate effective doses from total implanted activity. The latter was approximated with a 10-mL vial inside the patient.ResultsThe $\dot{K}$ measurements showed a low correlation with the total implanted activity, albeit an increasing trend of $\dot{K}$ was observed on increasing the activity. A stronger correlation was found between body mass index and $\dot{K}$ measurements.The effective dose to population is in general lower than dose constraints as well as the effective doses to relatives, with the exception of children and pregnant women, who command special precautions. We report differences between the experimental model– and theoretical model–based dose evaluation together with their comparison with previous studies found in literature.ConclusionsBased on the $\dot{K}$ measurements and the results of the present analysis, it is possible to provide the patient with radiation safety instructions specifically tailored to his relatives’ habits and working environment.     

Surface treatments of silver rods with enhanced iodide adsorption for I-125 brachytherapy seeds

This study described an effective method to load ¹²⁵I on silver rods for the preparation of a brachytherapy source. We tested various ligands on the silver rod surface to screen the one with the highest adsorption and specific radioactivity. In addition, we investigated the effect of surface etching to increase the adsorption capability followed by the extended surface area. We also found that the use of an oxidant during iodide adsorption can increase the loading significantly. The maximum activity of 137.90 MBq/rod (3.7269 mCi/rod) was achieved on the etched silver rods with phosphate ligand and hydrogen peroxide as an oxidant. In addition, this is 4.5-fold higher than that of the conventional chloride treatment method.     

Scintigraphic detection of 125I seeds after permanent brachytherapy for prostate cancer.

The purpose of this investigation was to monitor the localization and migration of 125I seeds after permanent brachytherapy for prostate cancer using a new scintigraphic technique that may overcome the drawbacks of conventional x-ray methods. METHODS: 125I seeds emit gamma-rays with an average energy peak of 28 keV. We used a gamma-camera equipped with low-energy high-resolution collimators that were tuned to an energy level of 35 keV with a 70% window width. Sixteen patients with prostate cancer were examined after 125I seed insertion. The number of seeds remaining in the prostate was confirmed using pelvic CT for postoperative dose planning; however, seeds that had migrated outside the prostate could not be detected. Furthermore, the migrated seeds were not completely traceable using chest or abdominal radiography. Thus, we adopted a scintigraphic technique to perform this task. The evaluation of radiography and scintigraphy findings was masked, and the rates of migrated seed detection were statistically examined using the McNemar test. To localize the migrated seeds, we fused the scintigraphic images of the migrated seeds and the patients' contours. RESULTS: Scintigraphy was successfully used to detect 20 migrated seeds of a total of 1,182 implanted seeds, whereas radiography was successfully used to detect 7. The sensitivity of the scintigraphy results was 20 of 20 (100%), whereas that of the radiography results was 7 of 20 (35%). Seed migration was detected in 11 of 16 patients (69%) using scintigraphy, whereas seed migration was detected in only 4 patients (25%) using radiography; this difference was statistically significant (P = 0.016). CONCLUSION: Scintigraphy is more effective for detecting seed migration and monitoring the localization of 125I seeds than radiography. The precise anatomic location of migrated seeds can be pinpointed using fusion images. Scintigraphy may become a standard procedure for monitoring seed migration during 125I brachytherapy in patients with prostate cancer.     

Permanent prostate brachytherapy monotherapy with I-125 for low- and intermediate-risk prostate cancer: Outcomes in 974 patients

Purpose

To report outcomes of patients undergoing low-dose-rate (LDR) brachytherapy and investigate factors associated with biochemical failure and survival.

Simple, accurate, safe, and cost-effective percutaneous transperineal template technique for permanent 125iodine interstitial brachytherapy of prostate cancer

We present the technique, intraoperative and postoperative complications of percutaneous transperineal template permanent 125iodine interstitial brachytherapy of prostate cancer. The percutaneous transperineal template permanent iodine interstitial brachytherapy under "C-arm" fluoroscopic guidance is a simple, easily-learned, accurate and rapid procedure which can be performed without subjecting the patient to celiotomy. We have treated 58 patients by the transperineal percutaneous permanent interstitial brachytherapy. 33 of 58 patients also had a staging celiotomy just prior to the brachytherapy. In the group of 22 patients undergoing brachytherapy without celiotomy and without adjuvant external-beam pelvic radiotherapy, there were no major complications. Blood transfusions were not required by any patients who underwent percutaneous transperineal permanent iodine interstitial brachytherapy without celiotomy.     

New approach of ultra-focal brachytherapy for low- and intermediate-risk prostate cancer with custom-linked I-125 seeds: A feasibility study of optimal dose coverage

PurposeTo present the feasibility study of optimal dose coverage in ultra-focal brachytherapy (UFB) with multiparametric MRI for low- and intermediate-risk prostate cancer.Methods and MaterialsUFB provisional dose plans for small target volumes (<7 cc) were calculated on a prostate training phantom to optimize the seeds number and strength. Clinical UFB consisted in a contour-based nonrigid registration (MRI/Ultrasound) to implant a fiducial marker at the location of the tumor focus. Dosimetry was performed with iodine-125 seeds and a prescribed dose of 160 Gy. On CT scans acquired at 1 month, dose coverage of 152 Gy to the ultra-focal gross tumor volume was evaluated. Registrations between magnetic resonance and CT scans were assessed on the first 8 patients with three software solutions: VariSeed, 3D Slicer, and Mirada, and quantitative evaluations of the registrations were performed. Impact of these registrations on the initial dose matrix was performed.ResultsMean differences between simulated dose plans and extrapolated Bard nomogram for UFB volumes were 36.3% (26–56) for the total activity, 18.3% (10–30) for seed strength, and 22.5% (16–38) for number of seeds. Registration method implemented in Mirada performed significantly better than VariSeed and 3D Slicer (p = 0.0117 and p = 0.0357, respectively). For dose plan evaluation between Mirada and VariSeed, D₁₀₀% (Gy) for ultra-focal gross tumor volume had a mean difference of 28.06 Gy, mean values being still above the objective of 152 Gy. D₉₀% for the prostate had a mean difference of 1.17 Gy. For urethra and rectum, dose limits were far below the recommendations.ConclusionsThis UFB study confirmed the possibility to treat with optimal dose coverage target volumes smaller than 7 cc.     

The retrospective analysis of the relationship between prescribed dose and risk factor for seed migration in iodine-125 prostate brachytherapy

Purpose

The aim was to determine the dose-specific incidence and predictors of seed loss/migration after permanent seed implantation (PI) for localized prostate cancer.

Materials and methods

The records of 79 patients with T1c–T3a prostate cancer who underwent prostate brachytherapy with loose iodine-125 seeds were retrospectively reviewed. Of these patients, 33 with low or intermediate risk underwent PI with the prescribed dose of 160 Gy for the clinical target volume (CTV), and 46 with high risk underwent PI with 110 Gy for the CTV followed by external beam radiotherapy (EBRT) with 45 Gy. Each CTV was defined as a contoured prostate. After PI, the incidence of seed loss/migration was assessed by a series of radiographs.

Results

Seed migration occurred in 22 (0.479 %) of 4589 implanted seeds 1 month after implantation. In PI alone, the number of needles (P = 0.081) and the number of seeds (P = 0.071) showed a trend for a difference between those with and without seed loss. In PI + EBRT, there was a significant difference in the discrepancy between the seed numbers calculated by the nomogram and actually implanted (P = 0.032).

Conclusions

It is suggested that the discrepancy in seed numbers might be the predictor for seed migration in PI with 110 Gy.

     

Preliminary study of correction of original metal artifacts due to I-125 seeds in postimplant dosimetry for prostate permanent implant brachytherapy

Purpose

We investigated a subtraction-based reprojection approach to reduce CT metal artifacts due to I-125 seeds and evaluated the clinical implications in postimplant dosimetry for prostate permanent implant brachytherapy.

Materials and Methods

The raw projection data were used to reduce metal artifacts due to I-125 seeds. CT images of the metal parts only were separated from the original CT images by setting the threshold for pixel value to that of the I-125 seeds. Using these images, sinograms of CT images with and without seeds were obtained by inverse Radon transform (iRT), and the sinogram of the metal image was subtracted from that of the original image. Finally, the image was reconstructed using the sinogram by Radon transform (RT). This technique was applied to a prostate phantom and to a patient undergoing prostate permanent implant brachytherapy.

Results

Metal artifacts from I-125 seeds were reduced in both the phantom and patient studies. This technique decreased the density of the inner region of seeds but enhanced the density of the seed edge, thereby facilitating the identification of seed number, orientation, and location.

Conclusion

This method reduces metal artifacts from I-125 seeds, and has potential for decreasing the time required for and improving the accuracy of postimplant dosimetry.     

Validation of the NCCN prostate cancer favorable- and unfavorable-intermediate risk groups among men treated with I-125 low dose rate brachytherapy monotherapy

PurposeTo validate the 2019 NCCN subgroups of favorable- and unfavorable-intermediate risk (IR) prostate cancer among patients treated with brachytherapy, who are underrepresented in the studies used to develop the 2019 NCCN classification.MethodsWe included all 2,705 men treated with I-125 LDR brachytherapy monotherapy at a single institution, and who could be classified into the 2019 NCCN risk groups. Biochemical failure and distant metastasis rates were calculated using cumulative incidence analysis.ResultsOf 1,510 IR patients, 756 (50%) were favorable-IR, and 754 (50%) were unfavorable-IR. Median follow up was 48 months (range, 3–214). As compared to favorable-IR, the unfavorable-IR group was associated with significantly higher rates of biochemical failure (HR, 2.87; 95% CI, 2.00–4.10; p < 0.001) and distant metastasis (HR, 3.14; 95% CI, 1.78–5.50, p < 0.001). For favorable-IR vs. unfavorable-IR groups, 5-year estimates of biochemical failure were 4.3% (95% CI, 2.6–6.1%) vs. 17.0% (95% CI, 13.6–20.5%; p < 0.001), and for distant metastasis were 1.6% (95% CI, 0.5–2.6%) vs. 5.4% (95% CI, 3.3–7.4%; p < 0.001), respectively. Patients with one unfavorable-intermediate risk factor (unfavorable-IRF; HR, 2.27; 95% CI, 1.54–3.36; p < 0.001) and 2–3 unfavorable-IRFs (HR, 4.42; 95% CI, 2.89–6.76; p < 0.001) had higher biochemical failure rates; similar findings were observed for distant metastasis (1 unfavorable-IRF: HR, 2.46; 95% CI, 1.34–4.53, p = 0.004; 2–3 unfavorable-IRFs: HR, 4.76; 95% CI, 2.49–9.10, p < 0.001).ConclusionsThese findings validate the prognostic utility of the 2019 NCCN favorable-IR and unfavorable-IR prostate cancer subgroups among men treated with brachytherapy. Androgen deprivation was not beneficial in any subgroup. Alternative treatment intensification strategies for unfavorable-IR patients are warranted.     

MRI-CT fusion to assess postbrachytherapy prostate volume and the effects of prolonged edema on dosimetry following transperineal interstitial permanent prostate brachytherapy

PURPOSE: Quality assurance through postplan assessment is an integral part of permanent seed prostate implants. The use of MRI-CT fusion for 1-month postimplant dosimetry permits accurate assessment of prostate volume without seed induced artifact and uncertainties of prostate contour inherent to CT assessments. Routine use of MRI-CT fusion reveals significant prostate edema may persist several weeks. This study evaluates the effect of edema, and its subsequent resolution, on dosimetry. METHODS AND MATERIALS: From May 2001 to June 2003, 241 men were treated with (125)I seed implants based on a transrectal ultrasound (TRUS) preplan. Quality assessment was performed at 1 month by CT-MRI fusion using VariSeed software. Over this 24-month period, 29 patients (12%) with residual edema at 1 month (12-60% >TRUS plan volume), had repeat CT-MRI fusion at 2-4 months to reassess volume and dosimetry. Eleven of the 29 had received prior androgen ablation to shrink the prostate preimplant. RESULTS: For the entire group (n = 241), mean preimplant prostate volume was 33.7 cc and median postplan dosimetric parameters were: V100, 92.2%; D90, 153 Gy; and V150, 53%. For the 29 patients with prolonged edema, mean preimplant volume was 34.8 cc and 1-month volume was 46.1 cc (p <0.001). Mean volume reduction between 1 and 2 months was 13%. The decrease in prostate volume had a significant effect on dosimetry with median increase between 1 month and 2 months in calculated V100 of 9.5%, V150 22.6%, V200 30.1%, and D90 11.5%. CONCLUSIONS: Significant residual edema is seen 1-month postimplant in 12% of prostates and may have a profound effect on dosimetry. Further study is underway to characterize the time course of resolution of the edema, and to perform integral dosimetry based on the changing volume.     

Local seed displacement from Day 0 to Day 30 in I-125 permanent prostate brachytherapy: A detailed,computed tomography-based analysis

PURPOSETo accurately quantify local seed displacement from Day 0 to Day 30 for our brachytherapy procedure. To quantify seed loss/migration and to identify the locations from where seeds are missing.METHODS AND MATERIALSSeed displacements were analyzed in 62 consecutive patients, who received brachytherapy with stranded I-125 seeds. At the start of the procedure, four fiducial gold markers were implanted. At the end of the implantation procedure an in-room 3D CBCT scan (Day 0) was acquired for accurate seed localization. At Day 30 a regular CT scan was acquired. This CT scan was rigidly registered to the CBCT scan using the fiducials. Subsequently, the Hungarian method was used to find pairs of corresponding seeds. Displacements were calculated and missing seeds were identified.RESULTSLocal seed displacements are smaller than 5 mm for 76.3% of the seeds; 2.3% show displacements larger than 10 mm. The largest seed displacements are seen along the inferior-superior axis: on average 1.0 ± 3.2 mm in superior direction with respect to the intraprostatic fiducials. Largest displacements are seen at the inferior-lateral sides of the prostate. On average, the inferior seeds move 1.0 ± 2.8 mm in anterior and 1.8 ± 3.3 mm in superior direction. The percentage of missing seeds is 0.2% (8 out of 3893 seeds for 5 patients). Most of the missing seeds were also originally implanted at the inferior-lateral sides of the prostate.CONCLUSIONSLocal seed displacements and number of missing seeds are small, and predominantly occur around the apex.     

I-125 or Pd-103 for brachytherapy boost in men with high-risk prostate cancer: A comparison of survival and morbidity outcomes

PurposeBrachytherapy boost improves biochemical recurrence rates in men with high-risk prostate cancer (HRPC). Few data are available on whether one isotope is superior to another. We compared the oncologic and morbidity outcomes of I-125 and Pd-103 in men with HRPC receiving brachytherapy.Methods and MaterialsOf 797 patients with HRPC, 190 (23.8%) received I-125 or 607 received Pd-103 with a median of 45 Gy of external beam irradiation. Freedom from biochemical failure (FFBF), freedom from metastases (FFMs), cause-specific survival (CSS), and morbidity were compared for the two isotopes by the ANOVA and the χ² test with survival determined by the Kaplan–Meier method and Cox regression.ResultsMen treated with I-125 had a higher stage (p < 0.001), biological equivalent dose (BED) (p < 0.001), and longer hormone therapy (neoadjuvant hormone therapy, p < 0.001), where men treated with Pd-103 had a higher Gleason score (GS, p < 0.001) and longer followup (median 8.3 vs. 5.3 years, p < 0.001). Ten-year FFBF, FFM, and CSS for I-125 vs. Pd-103 were 77.5 vs. 80.2% (p = 0.897), 94.7 vs. 91.9% (p = 0.017), and 95.4 vs. 91.8% (p = 0.346), respectively. Men with T3 had superior CSS (94.1 vs. 79.5%, p = 0.001) with I-125. Significant covariates by Cox regression for FFBF were prostate specific antigen (PSA), the GS, and the BED (p < 0.001), for FFM PSA (p < 0.001) and GS (p = 0.029), and for CSS PSA, the GS (p < 0.001) and the BED (p = 0.022). Prostate cancer mortality was 7/62 (15.6%) for BED ≤ 150 Gy, 18/229 (7.9%) for BED >150–200 Gy, and 20/470 (5.9%) for BED >200 Gy (p = 0.029). Long-term morbidity was not different for the two isotopes.ConclusionsBrachytherapy boost with I-125 and Pd-103 appears equally effective yielding 10-year CSS of over 90%. I-125 may have an advantage in T3 disease. Higher doses yield the most favorable survival.