Radiation Oncology/Endometrium/Brachytherapy

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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**
Fractions	Dose/fx	Depth
3	7.0 Gy	0.5 cm
4	5.5 Gy	0.5 cm
5	5.0 Gy	0.5 cm
6	2.5 Gy	0.5 cm

OR

**HDR Alone**
Fractions	Dose/fx	Depth
4	8.5 Gy	Surface
5	6.0 Gy	Surface
6	4.0 Gy	Surface

**EBRT 45 Gy + HDR**
Fractions	Dose/fx	Depth
3	5-6 Gy	Surface
3	4.0 Gy	0.5 cm*

*from 2000 paper; no dose recommendation

for 0.5 cm depth in 2019 Compendium

OR

**EBRT 50.4 Gy + HDR**
Fractions	Dose/fx	Depth
2	6.0 Gy	Surface

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