# Radiation Oncology/Endometrium/Brachytherapy

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
* Endometrial Carcinoma: Main Page |
* Staging |
* Overview |
* Early Stage |
* Locally Advanced Stage |
* UPSC |
* Clear Cell |
* Brachytherapy |
* Recurrence |
* Randomized |
* GOG Trials |
* Leiomyosarcoma: Main Page |
Endometrial Brachytherapy

## Adjuvant vaginal brachytherapy
### Overview

* Treat upper proximal 3–5 cm for endometrioid, treat entire vagina for clear cell and UPSC
* For ICRT only: LDR dose 50-60 Gy at 0.5 cm depth over 72 hrs (70-80 cGy/hr). HDR dose 21 Gy (7 Gy x 3 at 0.5 cm).
* For EBRT + ICRT: LDR dose 30 Gy. HDR dose 15 Gy (5 Gy x 3 at 0.5 cm) or 6 Gy x 3 (at surface).

### American Brachytherapy Society

* HDR Recommendations; 2000 PMID 11020575 — "The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the endometrium." Nag S et al. Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):779-90.
** Prescription documentation: Treatment site, radionuclide, prescribed absorbed dose, fractionation, prescription point, type of applicator, optimization points, method of optimization, number of dwell positions, relative dwell weights, isodose distribution
** Localization: Use localization radiographs in treatment position
** Doses: see table below
** Dose specification:
*** Endometrioid: treat proximal 3–5 cm of the vagina
*** Clear cell and UPSC: treat entire vaginal canal
*** Prescribe to either surface or 0.5 cm depth
*** Report both surface and depth doses
*** Place optimization points on both lateral surfaces, along the curved portion of the cylinder dome, and at the apex
*** Use proper anisotropic calculations
** Optimization:
*** Dose distribution should satisfy physician requirements, not just optimization specs
*** Dwell positions should not extend beyond target to avoid overdosing normal structures
*** High-dose heterogeneity within normal tissues is not acceptable
*** Process should not be too time-consuming
** Treatment review (second check):
*** Dosimetry data are correct
*** Absorbed dose prescription point, absorbed dose per fraction, number of fractions are per facility protocol
*** Absorbed dose distribution plan matches the prescription
*** Reconstructed applicator geometry matches the radiograph
*** Distance from machine reference point to the most distant dwell position is consistent with treatment plan
*** Absorbed doses to normal tissues are within tolerances
*** Dwell times for the generated plan are within a range consistent with those for similar patients
*** Programmed treatment data (dwell times, locations, step sizes) match those on the plan
*** Subsequent fractions using the same plan are performed with the correct data and the current source activity, and treatment time is adjusted accordingly
*** HDR source activity for the treatment day is corrected for source decay in the treatment planning system/console computer and verified by a separate independently calculated source decay chart or method
** Other checks for multifraction treatment
*** Use of correct applicator for each fraction
*** Reproduced applicator position
** Doses
*** To calculate LDR equivalent, use dose-modifying factor 0.7 for late effects
*** Recommended doses in tables below (now updated for 2019 publication), depending on EBRT and prescription depth:
* Brachytherapy Fractionation Choices; 2019 PMID 30979631 — "Compendium of fractionation choices for gynecologic HDR brachytherapy - An American Brachytherapy Society Talk Group Report." Albuquerque K et al. Brachytherapy. 2019 Jul-Aug;18(4):429-36.
HDR Alone :
| HDR Alone Fractions Dose/fxDepth 37.0 Gy0.5 cm 45.5 Gy0.5 cm 55.0 Gy0.5 cm 62.5 Gy0.5 cm | OR | HDR Alone Fractions Dose/fxDepth 48.5 GySurface 56.0 GySurface 64.0 GySurface |
EBRT 45 Gy + HDR :
| EBRT 45 Gy + HDR Fractions Dose/fxDepth 35-6 GySurface 34.0 Gy0.5 cm* *from 2000 paper; no dose recommendation for 0.5 cm depth in 2019 Compendium | OR | EBRT 50.4 Gy + HDR Fractions Dose/fxDepth 26.0 GySurface |
* Practice Survey; 2005 PMID 16109462 — "American Brachytherapy Society survey regarding practice patterns of postoperative irradiation for endometrial cancer: current status of vaginal brachytherapy." Small W Jr et al. Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1502-7.
** Most common doses listed
** Brachytherapy alone:
*** LDR: 60 Gy at surface; 47-60 Gy at 0.5 cm (mean 47.9 Gy, median 50 Gy, mode 60 Gy)
*** HDR: 7 Gy x 3 at 0.5 cm
** Boost after EBRT:
*** LDR: 30 Gy at surface, 20 Gy at 0.5 cm
*** HDR: 5 Gy x 3 at 0.5 cm

### Dose Prescriptions

Examples of HDR and LDR prescriptions see also ABS recommendations above
* PORTEC-2 Protocol
** For brachytherapy alone:
*** LDR 30 Gy at 0.5 cm
*** HDR 7 Gy x 3 at 0.5 cm
* RTOG / GOG
** RTOG 99-05 / GOG 0194
*** Boost dose: (after 50.4 Gy)
**** LDR 20 Gy at surface (at dose rate 0.8-1.2 Gy/hr)
**** HDR 6 Gy x 2 at surface (=12 Gy)
** RTOG 97-08
*** Boost dose: (after 45 Gy)
**** LDR 20 Gy at surface (at dose rate 0.8-1.2 Gy/hr)
**** HDR 6 Gy x 3 at surface (=18 Gy)

### Dose Evaluation

* Oreboro; Sweden (1989–2003)
** Randomized. 290 low-risk (endometrioid, Stage IA-B, Grade 1–2, <50% myometrial infiltration, diploid DNA, pLN-, washings-), Stage IA 62%, Stage IB 38%. Vaginal cylinders 20–30 mm, dose prescription 5mm depth. All received 6 fractions in 8 days, randomized to Arm 1 2.5 Gy/fractions (total 15 Gy) or Arm 2) 5.0 Gy/fx (total 30 Gy). Colpometric measurements of vaginal shortening pretreatment and at 5 years
** 2005 PMID 16029797 -- "Intravaginal high-dose-rate brachytherapy for stage I endometrial cancer: a randomized study of two dose-per-fraction levels." (Sorbe B, Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1385-9.)
*** Outcome: CSS 98.5% (NS), OS 95.3% (NS), no distant mets. Recurrence 1.4% (NS), 0.7% pelvic (NS) and 0.7% vaginal (NS)
*** Toxicity: no vaginal shortening for 2.5 Gy/fx group (pre vs. post) compared with 25% vaginal shortening (mean 2.1 cm) for 5.0 Gy/fx group. Also more vaginal atrophy and mucosal bleeding in 5.0 Gy/fx group
*** Conclusion: Recommend six fractions of 2.5 Gy/fx in low-risk endometrial Ca

### Placement

* Mt. Vernon; 2002 (UK) PMID 11932216 -- "The influence of applicator angle on dosimetry in vaginal vault brachytherapy." (Hoskin PJ, Br J Radiol. 2002 Mar;75(891):234-7.)
** 30 patients. Dosimetric evaluation of "natural" insertion angle vs. horizontal insertion angle (determined by a level). Prescription 5.5 Gy at 0.5 cm depth. ICRU rectal and Bladder points used
** Outcome: Mean change in angle of 19.7 degrees, resulting in mean absolute dose reduction of 1.3 Gy to rectum, but increase of 0.5 Gy to bladder
** Conclusion: Vaginal BT should be performed in "corrected" horizontal position to reduce bowel dose at expense of bladder dose

### Retrospective

With pelvic radiotherapy:
* Wake Forest, 1990 - PMID 2380095 — "Role of intracavitary cuff boost after adjuvant external irradiation in early endometrial carcinoma." Randall ME et al. Int J Radiat Oncol Biol Phys. 1990 Jul;19(1):49-54.
** Retrospective. 157 pts. Treated with surgery + external beam RT. Compared pts with or without vaginal cuff boost of 30-50 Gy surface dose.
** No difference in local control (but higher risk features in the group receiving brachy).
** Conclusion: Adding vaginal cuff boost to EBRT does not improve local control
Brachytherapy alone:
* Meta-Analysis; 2000 PMID 10869750 -- "Post-operative high dose rate brachytherapy in patients with low to intermediate risk endometrial cancer." (Pearcey RG, Radiother Oncol. 2000 Jul;56(1):17-22.)
** Literature review. 13 series, 1800 cases. Wide range of fractionation schedules; BED calculated using LQ model
** Outcome: vaginal control rate 99%. No threshold for tumor control, moderate dose (BED10 ~50 Gy) appeared tumoricidal with control rate at least 98%. 3 series using 21/3 showed 0% toxicity and 98-100% control rate
** Toxicity: BED3 >100 Gy predicted for late complications
** Conclusion: HDR brachytherapy yields high local control and extremely low morbidity using modest dose fractionation schedules
* Eltabbakh, Roswell Park - PMID 9226326 — "Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial." Eltabbakh GH et al. Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):373-80.
** 303 pts. Stage 1B, Grades 1–2, treated with hysterectomy only without lymph node staging, then LDR brachytherapy to 30 Gy to 0.5 cm depth. 10, 20, and 30-year DFS were >95% (median 8 yr f/u).

### HDR Dose Models

* Ohio State; 2000 PMID 10661360 — "A simple method of obtaining equivalent doses for use in HDR brachytherapy." (Nag S, Int J Radiat Oncol Biol Phys. 2000 Jan 15;46(2):507-13.)
** Microsoft Excel based program that applies the LQ formula to calculate BED for various fractionation schemes, and reconverts it to "standard" (2 Gy/fx) fractionation

## Toxicity

* Please see the Vagina toxicity page

## Other References

* "Endometrial Cancer" (Potter R, Gerbaulet A, Haie-Meder C) chapter from the "GEC ESTRO Handbook of Brachytherapy" Gerbaulet, Alain; Pötter, Richard; Mazeron, Jean-Jacques; Meertens, Harm; Limbergen, Erik Van, eds. (2002). Leuven, Belgium: European Society for Therapeutic Radiology and Oncology. OCLC 52988578.
* Gynecol Oncol 2015 Review PMID 25555710 — "The role of vaginal cuff brachytherapy in endometrial cancer." Harkenrider MM, et al. Gynecol Oncol. 2015 Feb;136(2):365-72.
** Good review of brachytherapy