A Randomized Trial of High and Low Source Strength I-125 Prostate Seed Implants

Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 22, 2003

Presenter: Vrinda Narayana, MD
Presenter's Affiliation: University of Michigan
Type of Session: Scientific


    Prostate brachytherapy is an established treatment modality for early, localized adenocarcinoma of the prostate. Selected patients with low-risk features based on clinical stage, Gleason score, and serum PSA level can undergo permanent prostate seed implantation as an alternative to radical prostatectomy or external beam radiation. The preferred seed isotope for permanent implants is I-125, but a range of source activities (0.3-1.3 U or 0.25-1 mCi) can be used, as no consensus exists on this matter. This study sought to compare high and low strength I-125 seed strengths from the perspective of implant quality, cost, and toxicity. The investigators' hypothesis was that no difference would be demonstrated between the two groups.

Materials and Methods

  • 40 patients randomized to receive either:
    1. high seed strength (0.76 U, ~0.6 mCi) implant
    2. low seed strength (0.4 U, ~0.3 mCi) implant
  • Treatment population was a mix of patients undergoing primary brachytherapy treatment (n=10) and patients receiving boost treatment (n=30)
  • The primary and boost patients were comparably matched in both arms.
  • Primary tx pts were treated to 145 Gy while boost tx pts were treated to 108 Gy
  • Patients were all implanted by the same team
  • Ultrasound-guided image planning in the OR using Variseed software and I-125 rapid strands; seed drop-off monitored with fluoroscopy
  • Average prostate gland size = 40 cc
  • Average number of seeds: high = 60 +/-16; low = 96 +/-13
  • Post-implant dosimetric evaluation about 15 days later using CT scan and T2-weighted MRI images, the latter considered more precise than the former
  • CT dosimetry: source positions obtained by autorecognition on 2-mm slices.
  • MRI dosimetry: CT and MRI images registered using mutual information, MRI dosimetry derived from CT source positions.
  • Endpoints of interest included the following implant quality parameters:
    1. dose index, defined as the ratio of achieved dose to planned dose for CT and MRI as a measure of relative error tolerance; used to avoid inter-patient bias
    2. volume receiving prescribed dose (V100)
    3. cost of source and OR time
    4. acute toxicity based on obstructive/irritative symptom score


  • No statistically significant difference in total implanted source strength between arms: p<0.27 high strength arm = avg 48.3 U (+/-12.8) low strength arm = avg 43.8 U (+/-12.9)
  • D90, the dose to 90% of the prescribed volume, was higher in the high strength arm using both CT and MRI dosimetry:
    • CT D90 = 1.24 (+/-0.18) in high strength
    • CT D90 = 1.09 (+/-0.21) in low strength pMRI D90 = 1.07 (+/-0.23) in high strength
    • MRI D90 = 0.87 (+/-0.21) in low strength p
    • Statistically significant differences were found favoring the high strength source over the low strength source in all of the following parameters:
      1. better dose index (dose coverage ratio)
        D80 (0.90 vs. 0.79 p=0.006)
        D90 (0.78 vs. 0.64 p=0.003)
        D95 (0.73 vs. 0.50 p=0.001)
        D99 (0.66 vs. 0.51 p=0.001)
      2. larger V100 : 95.8 (+/-3.8) vs. 91.7 (+/-5.3) plower seed cost : $2880 vs. $4725 per patient
        primary tx = $3200 vs. $6040
        boost tx = $2400 vs $3840
      3. less OR time : 66 min (+/-16) vs. 84 min (+/-21) p
      4. No statistically significant differences in rectal wall or urethra dose by MRI.
      5. No statistically significant difference in acute symptom scores, although average scores were a little higher in the high-source arm.

    Author's Conclusions

    • High activity I-125 prostate seeds have a greater error tolerance, consistent with prior theoretical predictions.
    • High source strength seeds also have a lower average cost with comparable acute toxicity profile to the low strength seeds.
    • If long-term toxicity does not differ, high source strength seeds are preferable in terms of implant quality, patient tolerance, and healthcare economics.

    Clinical/Scientific Implications

      This study offers important randomized data on an area of prostate brachtherapy that has thus far lacked a general consensus. The results of this study certainly appear to support the use of high strength I-125 seeds for superior tumor coverage and treatment planning reproducibility. Furthermore, the high activity seeds are associated with savings of cost and time compared to low activity seeds. Although some may criticize the small patient sample size, this study aimed to perform dosimetric evaluation, which is a continuous variable for which a population of 40 patients should actually provide sufficient power. Of note, the authors emphasize that the high activity planning strategy involved very lateral and peripheral seed placement, with minimal correction needed compared to the low activity implants, for which correction is crucial.

    Oncolink's ASTRO Coverage made possible by an unrestricted Educational Grant from Siemens Medical Solutions.