1. Permanent Interstitial Implants Ideal strategy to curatively manage small volume gynecologic malignancies Can deliver high cumulative radiation dose to tightly conformal volumes. Reduces toxicity compared to external RT. Use currently limited due to lack of familiarity/experience with this modality Revival of interest in interstitial implants with supporting clinical data and development of safer, low energy sources with better decay characteristics (half-life, energy, dose rate)

2. Brabham JG, Cardenes HR. Am J Clin Oncol 2009; 32:417- 422.

3. N=19

7. Results Median age: 76 years (range, 38–87) Median tumor volume: 3.3 cm 3 (range, 0.8 –21.3) Median previous radiation dose: 67 Gy (range, 38.7– 91.6) Median prescribed dose: 50 Gy (range, 25–55) Median follow-up: 21 months CR rate 94.7% LC rate 63.1% (ultimately achieved in 78.9%) 52.6% of patients were alive with no evidence of disease One grade 3 toxicity (5.3%) Brabham JG, Cardenes HR. Am J Clin Oncol 2009; 32:417-422.

8. Conclusions regarding IRI using Au- 198 198 Au-IRI is a safe, cost-effective, and reasonably efficacious method for controlling locally recurrent, low-volume, well-selected gynecologic malignancies, and treated with previous full-dose radiotherapy. It represents a reasonable potential therapeutic option in the salvage setting in patients who meet these criteria, particularly in women who are not candidates for or are unwilling to undergo radical salvage surgery. Brabham JG, Cardenes HR. Am J Clin Oncol 2009; 32:417-422.

9. UK Experience with Permanent Isotopes in Gynecologic Cancers 30 year experience with permanent Au 198, particularly in gynecologic cancers (Randall) No known experience to evaluate the safety/efficacy of Cs 131 in gynecologic malignancies Hypothesized Cs 131 efficacy would be at least equivalent to Au 198 with the added benefit of lower radiation exposure for occupationally exposed personnel Based on 4+ years of experience, UK is exclusively utilizing Cs 131 for permanent interstitial brachytherapy for gynecologic malignancies

10. Favorable properties of Cesium-131 Short ½ life translates into high initial dose rate (9.7 days vs. 2.7 days for Au-198) Lower energy (30.4 KeV vs 400 KeV for Au-198) translates into adequate dose distribution with better radiation safety* Relative equivalence to Au 198 facilitating clinical dosing/conversions

11. UK Dosimetric Modeling Ran multiple Monte Carlo simulations to evaluate optimal distribution of activity (essentially Quimby vs Manchester rules). Goal was adequate coverage and homogeneity of dose distribution. Determined that optimal planning was based on Paterson-Parker (Manchester) rules for permanent implants (uneven distribution of activity to create more homogeneity) To determine doses, used BED formalism to estimate, then adopted correction factor (compared to Au 198 ) based on clinical experience = 1.1 Luo W, Molloy J, Aryal P, Feddock J, Randall M. Med Phys., 41 (2): 024101 (2014 ).

12. University of Kentucky Experience with Cs-131 Recently published results of initial 14 patients treated with a total of 17 Cs-131 implants Included spectrum of gynecologic sites and pathologies for primary and recurrent cancers Seven implants performed as a boost Wooten CE, Randall ME, … Feddock J. Implementation and Early Clinical Results utilizing Cs-131 permanent interstitial implants for gynecologic malignancies. Gyn Oncol 2014;

13. Wooten CE, Randall ME, … Feddock J. Implementation and Early Clinical Results utilizing Cs-131 permanent interstitial implants for gynecologic malignancies. Gyn Oncol 2014.

14. Local Control Actuarial local control at 12 months = 84.4% Two local failures occurred 5 and 7 months after the implant One patient was able to gain local control through re-implantation The second received a dose of 44 Gy to largest implant area of 17.5 cm 3 Wooten CE, Randall ME, … Feddock J. Implementation and Early Clinical Results utilizing Cs-131 permanent interstitial implants for gynecologic malignancies. Gyn Oncol 2014.

15. Table 2 Radiation dose characteristics of additional Cs-131 implants following initial implant by patient Patient # Implant # Volume (cm 3 ) Indication Cs-131 dose (Gy) Total tumor treatment dose (Gy)* Total dose to treated area (Gy) † Local control Regional Control 623.14 Regional vaginal recurrence 33 102.30NoYes 631.77 Partial response to implant #2 4578147.30Yes 723.14 Separate vaginal recurrence 50 93.10Yes * Combined treatment dose to tumor including Cs-131 implant with external beam radiation and brachytherapy calculated using EQD2 † Cumulative estimated dose to the treated area from contributions of previous radiation therapy and total tumor treatment dose Wooten CE, Randall ME, … Feddock J. Implementation and Early Clinical Results utilizing Cs-131 permanent interstitial implants for gynecologic malignancies. Gyn Oncol 2014.