# Radiation Oncology/Endometrium/Recurrence

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Treatment of recurrent disease

## Vaginal and/or nodal recurrence

* GOG 238 (2008 - 2020) - RT vs cisplatin-RT
** Randomized. 165 patients. Recurrent endometrial cancer confined to vagina and/or lymph nodes. 1) Arm 1 - EBRT 45/25. Boost with HDR intracavitary brachy (60%), interstitial brachy (~12%), or EBRT boost to 65+ Gy (~25%). 2) Arm 2 - radiation + weekly cisplatin 40 mg/m2 weekly. Median age 66 years. Majority grade 1-2 endometrioid (82%) and vaginal only recurrence (86%)
** 2024 PMID 38662968 -- "Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial" (Klopp AH, J Clin Oncol. 2024 Apr 25:JCO2301279. doi: 10.1200/JCO.23.01279. Online ahead of print.)
*** Outcome: PFS RT only 63% vs CRT 57% (NS). Median OS 8.0 years vs. 8.3 years (NS). Most common further recurrence vagina (30% vs 20%), pelvis (25% vs 10%), abdomen (26% vs 20%), liver (0% vs 10%), lung (9% vs 20%)
*** Toxicity: Acute effects worse for chemo-RT group, except for GI symptoms. Long terms effects no difference.
*** Conclusion: Radiation therapy alone can results in good outcomes, chemotherapy does not improve PFS and increases toxicity

## Vaginal recurrence

* UC San Francisco; 2017 PMID 28802913 -- "Salvage high-dose-rate brachytherapy and external beam radiotherapy for isolated vaginal recurrences of endometrial cancer with no prior adjuvant therapy." (Chapman CH, Brachytherapy. 2017 Nov - Dec;16(6):1152-1158. doi: 10.1016/j.brachy.2017.07.002. Epub 2017 Aug 10.)
** Retrospective. 30 patients. Median time to recurrent 17 months. Pelvic RT 45-50.4 in 25-28 fractions. Interstitial brachy in 90%, median EQD2 68 Gy. Median F/U 6.3 years
** Outcome: 5-year locoregional control 87%. 5-year PFS 75%, CSS 83%, OS 77%. If grade 3 disease, 5-year OS 29% vs 95% (SS). If Stage >IA, 5-year CSS 74% vs 93% (SS)
** Conclusion: Salvage EBRT and HDR brachytherapy high rate of locoregional control
* University of Pittsburgh; 2014 (2004-2013) PMID 25241996 -- "Definitive salvage for vaginal recurrence of endometrial cancer: the impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1 risk stratification." (Vargo JA, Radiother Oncol. 2014 Oct;113(1):126-31. doi: 10.1016/j.radonc.2014.08.038. Epub 2014 Sep 18.)
** Retrospective. 41 patients undergoing definitive salvage RT. Pelvic IMRT 45/25, followed by HDR brachytherapy (median 23.75 Gy in 5 fractions). Median F/U 18 months
** Outcome: 3-year LC 95%; distant control 61%; RFS 68%, OS 67%.
** Toxicity: No grade 3+ acute toxicity. Late grade 3+ toxicity 8%
** Conclusion: Salvage IMRT plus HDR brachytherapy show excellent control and minimal morbidity
* Washington U., 2005 (1967-2003) PMID 16168841 — "Definitive radiotherapy in the management of isolated vaginal recurrences of endometrial cancer." Lin LL et al. Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):500-4.
** Retrospective. 50 pts treated for recurrence after tah/bso. Treatment was EBRT alone (6%), brachytherapy alone 16%, or EBRT + brachy (78%). Median dose to recurrence 60 Gy.
** Median f/u 58 mo. 5-yr and 10-yr DFS 68% and 55%, OS 53% and 40%.
** Conclusion: cure is possible in over 50% of pts.
* MDACC, 2003 (1960-97) PMID 12873682 -- "Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma after hysterectomy." (Jhingran A, Int J Radiat Oncol Biol Phys. 2003 Aug 1;56(5):1366-72.)
** Retrospective, 91 pts. Treatment was EBRT alone (31%), brachy alone (12%), or EBRT + brachy (57%). Median total dose 75 Gy; median EBRT dose 50 Gy.
** Median f/u 58 mo. LC 2yr-85%, 5yr-75%; OS 2yr-69%, 5yr-43%. Combination treatment was associated with better control.
** Conclusion: RT provides excellent LC
* PORTEC-1, 2003 (1990-97) PMID 12713981 -- "Survival after relapse in patients with endometrial cancer: results from a randomized trial." (Creutzberg CL, Gynecol Oncol. 2003 May;89(2):201-9.)
** Patients treated in the PORTEC trial (see here), randomized to either adjuvant RT or observation.
** 39 pts with isolated vaginal relapse; 31 of these treated with curative intent (usually RT+brachy). CR obtained in 31 of 35 (89%), with long term control in 24 of 31 (77%). Total long term control rate is thus 24/35 (68%).
** Survival after 1st relapse at 3 yrs: 51% (control group) vs 19% (RT).
** Survival after vaginal relapse 73%, after pelvic relapse 8%, after DM relapse 14%.
HDR Brachytherapy:
* Montreal (Hôpital Notre-Dame) (1997-2003)
** 2006 PMID 16386785 -- "Salvage treatment with high-dose-rate brachytherapy for isolated vaginal endometrial cancer recurrence." (Petignat P, Gynecol Oncol. 2006 Jun;101(3):445-9.)
** 22 pts; 18 treated with combined EBRT + HDR, and 4 with HDR alone. Median EBRT dose 45 Gy. Brachytherapy dose median 26 Gy (range: 8-48 Gy).
** CR in 100%. No LR after median f/u of 32 mo.
** Conclusion: salvage treatment with EBRT + HDR is efficacious
* McGill University
** 1997 PMID 9264580 -- "Isolated vaginal recurrences in endometrial carcinoma: treatment results using high-dose-rate intracavitary brachytherapy and external beam radiotherapy." (Pai HH, Gynecol Oncol. 1997 Aug;66(2):300-7.)
** 20 pts; 13 treated with combined EBRT + HDR, and 7 with HDR alone. Median EBRT dose 44 Gy and 24 Gy HDR to vaginal surface. For HDR alone, median dose 35 Gy.
** CR in 90%. 10-yr LC 74%.
** Conclusion: salvage treatment with EBRT + HDR is efficacious