Morbidity / ComplicationsPatients experienced only expected post-implant reactions

Two patients with self-limited superficial necrosis of vaginal mucosa

No hospitalizations, fistulas or other severe side effects

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

WHAT IF THERE WERE A TREATMENT FOR RECURRENT GYNECOLOGIC CANCERS WITH:

A SIGNIFICANT SALVAGE RATE (CURE), andLIMITED MORBIDITY, andAT A REASONABLY LOW COST?

THERE IS SUCH A TREATMENT FOR SELECTED PATIENTS: INTERSTITIAL RE-IRRADIATION.

DON’T FORGET ABOUT IT!

Use of Cesium-131 in Definitive Therapy for Gynecologic Malignancies

Primarily used as a boost:Adjuvantly for a positive margin (vaginal cuff post hysterectomy)

Definitively to treat gross diseaseUnresectable diseaseSmall volume residual following standard therapy

Ideally reserved for patients considered unsuitable for treatment using Syed-Neblett either for medical or logistical reasons

UK Experience using Cs-131 as a component of primary therapy

N=18Median age: 66 (37-87)

Type of Cancer N=

Recurrent Endometrioid AdenoCa 5

Post-operative Endometrioid AdenoCa 4

Post-operative Cervical SCCa 2

Primary Vaginal AdenoCa 3

Vaginal Melanoma 2

Vulvar SCCa 2

Characteristics of Cs-131 Implants used for Primary Therapy

Total implants performed: 18

Median dose = 22 Gy (15-50 Gy)Median seed count = 13 (9-30)Median source strength = 0.76 u/seed (0.48-1.8)Median area treated = 6 cm2 (2-19.25 cm2)

Indication for Cesium-131 Boost N=

Microscopic positive margin 4

Gross disease post-operatively 2

Gross disease at end of primary radiation 10

Gross disease before primary radiation (melanoma) 2

Results incorporating Cesium-131 into Initial Therapy

Median Follow-up 6.7 months (1-23.5 months)Disease control:

There have been no local failures – LC = 100%Only one patient has developed regional and/or metastatic disease

Patient with vaginal melanoma developed a confirmed inguinal lymph node recurrence at 8.2 months post treatment

Toxicity:Very low – nearly all develop acute grade 1-2 mucosal reactions that quickly resolveTwo patients have developed grade 3 mucosal reactions

One with persistent changes beyond 6 months

One patient has identified persistent grade 2 GU toxicity beyond 6 months

A Case of Vulvovaginal Melanoma40 Gy to 5mm using Cs-131

Additional 30 Gy using EBRT

2 weeks later

What can be gained by adding Interstitial Brachytherapy?

45 Gy PRT followed by ICB 7 Gy to 5mm depth x3Dose to 5mm Depth• BED = 88.8 Gy• EQD23 = 74.0 GyDose to Vaginal Surface• BED = 104.4 Gy• EQD23 = 87.0 GyDose to the Rectum (approx 5mm deep)

• EQD210 = 85.2 Gy– 7 Gy per implant delivered to the entire active

length treated

45 Gy PRT followed by ICB 7 Gy to surface x2 then 20 Gy Cs-131Dose to 5mm Depth• BED = 88.8 Gy• EQD23 = 73.0 GyDose to Vaginal Surface• BED = 97.4 Gy• EQD23 = 81.1 GyDose to the Rectum (approx 5mm deep)

• EQD210 = 70.2 Gy– 4.75-5 Gy per implant times active length– Receives prescription dose of Cs-131 implant,

but to length of 1-1.5cm

All calculations performed using GEC-ESTRO LQ Worksheet. http://www.americanbrachytherapysociety.org

Patient SelectionHow do we decide which type of implant to use?

Depth of the tumor< 5mm: vaginal cylinder will do fine

5mm – 1cm: permanent implant using Cesium-131 or Gold-198

≥ 1cm: Syed-Neblett or other catheter based treatment

Vaginal Cylinder Permanent Seeds Syed-Neblett

ConclusionsUK first to utilize/investigate Cs131 permanent interstitial implants for recurrent or new primary gynecologic malignancies.Actuarial local control rate at time of analysis was 84.4%, exceeding other published rates with minimal toxicity.Interstitial implants with Cs-131 should be more frequently and widely incorporated into management of gynecologic malignancies, including accessible recurrences following previous RT.

So How Do I Perform One?

42 year old female diagnosed with Stage II clear cell uterine cancer after TAH/BSO/LNSReceives adjuvant therapy:

45 Gy to the Pelvis followed by 6 cycles of Carbo/Taxol

Within first month off therapy develops vaginal bleeding

Biopsy proven recurrence at vaginal apex

Treated with Vaginal brachytherapy 30Gy/10 fractions BID to the surface

3 weeks post brachytherapy, exam demonstrates progressive tumor at the vaginal apex

MRI confirms this is only site of disease

Scheduled for Exenteration with Gyn Oncologist

Treated instead with Interstitial Re-irradiation using Cesium-131

2.5cm

4cm

Description of Procedure Gross tumor volume to be implanted determined based on three-dimensional tumor measurements based on pelvic exam and imagingTotal activity, seed strength, and geometry calculated using Paterson-Parker rulesOutpatient procedure in the Radiation Oncology DepartmentPremedication: 5-10 mg po DiazepamLocal anesthesia: 2% lidocaine ± epinephrineIndividual seed applicators to insert each seed

Plan to deliver 55 Gy to 3 x 4.5cm ellipse3cm

4.5cm

1. Determine the Area: π * A * B = π * 1.5 * 2.25 = 10.6 cm

A

B

2. Determine the necessary activity to deliver 10 Gy in Radium equivalent

3. Convert the activity in Radium equivalent to activity in Au-198:

8.25 R-cm2/mg-hr * 250 mg-hrs * 55 Gy = 51.09 mCi of Au-198

2.38 R-cm2/mg-hr 93.3 mg-hrs 10 Gy4. Convert the activity in Au-198 into activity in Cs-131 using conversion factor of 1.1:

51.09 mCi of Au-198 * 1.1 = 56.19 mCi of Cs-131

5. Determine the number of seeds necessary to perform the implant:

Using Paterson-Parker RulesArea <25 cm2 2/3 in the peripheral, 1/3 central

Circumference = 11.89 cmSpacing seeds evenly at 1cm increments – 12 seeds

will be needed

If 2/3 = 12, then 1/3 will equal 6

So total number of seeds = 18

6. Determine the activity needed per seed:

Total activity = 56.19 mCi of Cs-131 = 3.12 mCi/seed

Seed count 18 seeds

7. Convert to Air-Kerma Strength using factor of 0.638:

Air-Kerma Strength = 3.12 mCi/seed * 0.638 u/mCi = 1.99 u/seed

So, we need to order 18 seeds at 1.99 u/seed to deliver 55 Gy to 5mm depth

- I usually order 10% extra in order to account for tumor growth between calculation and implant date

- So we ordered #21 seeds