Radiation Oncology/Endometrium/Brachytherapy

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 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 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 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 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) 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 - 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 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 - 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 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 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