The value of a multimodal approach combining radical surgery and intraoperative radiotherapy in the recurrence treatment of gynecological malignancies - analysis of a large patient cohort in a tertiary care center.
Electron
Gynecological cancer
High-dose-radiotherapy
Intraoperative radiotherapy
Radiation therapy
Radical surgery
Recurrence
Journal
Radiation oncology (London, England)
ISSN: 1748-717X
Titre abrégé: Radiat Oncol
Pays: England
ID NLM: 101265111
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
26
06
2024
accepted:
11
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Recurrent and locally advanced gynecological malignancies have a poor prognosis. In particularly, pelvic local recurrence after previous radiotherapy and/or positive resection margins during surgical treatment for recurrent disease result in low survival rates. Consequently, locoregional control is of utmost importance in this cohort of patients. The aim of this study was to analyze treatment outcomes and determine prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for recurrent and locally advanced gynecological malignancies. 40 patients who underwent surgical treatment and IORT between 2010 and 2022 were eligible for inclusion. The median follow-up time was 22 months. The outcomes measured were locoregional control (LRC), overall survival (OS), and survival without distant metastases (DMFS). The Cox proportional hazards model was used for univariate and multivariate analysis to assess the impact of patient variables and treatment factors on the endpoints mentioned. The following variables were analyzed: age at surgical treatment and IORT and initial diagnosis (< 65 vs. ≥65 years, each), disease-free interval (DFI) between initial diagnosis and first recurrence, DFI to surgical treatment and IORT, grading, histology, IORT dose (≤ 13 vs. >13 Gy) and technique (high dose radiotherapy (HDR) vs. IORT using electrons, (IOERT)). Survival curves were generated using the Kaplan-Meier method. The mean IORT dose was 13.8 Gy (range 10-18 Gy). Cervical carcinoma was most frequently found in 27.5% of patients followed by endometrial carcinoma and vulvar carcinoma in 25% respectively. The final histopathologic results after surgery with IORT showed no residual tumour in 24 patients (60%), microscopic residual disease in 5 patients (12.5%), resection status could not be evaluated in three patients (7.5%) and the resection status was unknown in eight patients (20%). Subsequently, 27.5% of patients also received adjuvant radiotherapy of the local recurrence bed. However, after IORT, 65% of the women suffered a recurrence. Of these, the recurrences were localized: in-field 32.5%, out-of-field 22.5% and margin-of-field 12.5%. The 3- and 5-year OS was 69% and 55% respectively. The 3- and 5-year LRC was 56% respectively. The 3- and 5-year DMFS was 66% and 49%. Whereas the comparison between groups by IORT dose level (≤ 13 vs. >13 Gy) showed a non-significant trend in favor of the higher dose only for OS (p = 0.094), but not in LRC and DMFS (p > 0.05). OS and DMFS, but not LRC, differed significantly between the HDR-IORT and IOERT groups (p = 0.06 and p = 0.03,) in favor of the HDR-IORT technique. For HDR-IORT technique a trend towards superior OS and LRC was observed in the univariate analysis: HR 3.76, CI 95%: 0.95-14.881, p = 0.059 and HR 2.165 CI 95%: 0.916-5.114, p = 0.078 CONCLUSIONS: The survival rate for pelvic recurrence in gynecological malignancies remains poor and comparable with historical data from the last two decades. Particularly HDR-IORT, appears to provide a long-term oncological benefit in carefully selected patients.
Sections du résumé
BACKGROUND
BACKGROUND
Recurrent and locally advanced gynecological malignancies have a poor prognosis. In particularly, pelvic local recurrence after previous radiotherapy and/or positive resection margins during surgical treatment for recurrent disease result in low survival rates. Consequently, locoregional control is of utmost importance in this cohort of patients. The aim of this study was to analyze treatment outcomes and determine prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for recurrent and locally advanced gynecological malignancies.
METHODS
METHODS
40 patients who underwent surgical treatment and IORT between 2010 and 2022 were eligible for inclusion. The median follow-up time was 22 months. The outcomes measured were locoregional control (LRC), overall survival (OS), and survival without distant metastases (DMFS). The Cox proportional hazards model was used for univariate and multivariate analysis to assess the impact of patient variables and treatment factors on the endpoints mentioned. The following variables were analyzed: age at surgical treatment and IORT and initial diagnosis (< 65 vs. ≥65 years, each), disease-free interval (DFI) between initial diagnosis and first recurrence, DFI to surgical treatment and IORT, grading, histology, IORT dose (≤ 13 vs. >13 Gy) and technique (high dose radiotherapy (HDR) vs. IORT using electrons, (IOERT)). Survival curves were generated using the Kaplan-Meier method.
RESULTS
RESULTS
The mean IORT dose was 13.8 Gy (range 10-18 Gy). Cervical carcinoma was most frequently found in 27.5% of patients followed by endometrial carcinoma and vulvar carcinoma in 25% respectively. The final histopathologic results after surgery with IORT showed no residual tumour in 24 patients (60%), microscopic residual disease in 5 patients (12.5%), resection status could not be evaluated in three patients (7.5%) and the resection status was unknown in eight patients (20%). Subsequently, 27.5% of patients also received adjuvant radiotherapy of the local recurrence bed. However, after IORT, 65% of the women suffered a recurrence. Of these, the recurrences were localized: in-field 32.5%, out-of-field 22.5% and margin-of-field 12.5%. The 3- and 5-year OS was 69% and 55% respectively. The 3- and 5-year LRC was 56% respectively. The 3- and 5-year DMFS was 66% and 49%. Whereas the comparison between groups by IORT dose level (≤ 13 vs. >13 Gy) showed a non-significant trend in favor of the higher dose only for OS (p = 0.094), but not in LRC and DMFS (p > 0.05). OS and DMFS, but not LRC, differed significantly between the HDR-IORT and IOERT groups (p = 0.06 and p = 0.03,) in favor of the HDR-IORT technique. For HDR-IORT technique a trend towards superior OS and LRC was observed in the univariate analysis: HR 3.76, CI 95%: 0.95-14.881, p = 0.059 and HR 2.165 CI 95%: 0.916-5.114, p = 0.078 CONCLUSIONS: The survival rate for pelvic recurrence in gynecological malignancies remains poor and comparable with historical data from the last two decades. Particularly HDR-IORT, appears to provide a long-term oncological benefit in carefully selected patients.
Identifiants
pubmed: 39456020
doi: 10.1186/s13014-024-02537-z
pii: 10.1186/s13014-024-02537-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
147Informations de copyright
© 2024. The Author(s).
Références
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.
doi: 10.3322/caac.21660
pubmed: 33538338
Cancer Stat Facts: Cervical Cancer. (2023).: Cervical Cancer. (2023). National Cancer Institute. Retrieved; 2023 [ https://seer.cancer.gov/statfacts/html/ovary.html
Cancer Stat Facts: Uterine Cancer. (2023).: National Cancer Institute. Retrieved; 2023 [ https://seer.cancer.gov/statfacts/html/corp.html
del Carmen MG, McIntyre JF, Fuller AF, Nikrui N, Goodman A. Intraoperative radiation therapy in the treatment of pelvic gynecologic malignancies: a review of fifteen cases. Gynecol Oncol. 2000;79(3):457–62.
doi: 10.1006/gyno.2000.6002
pubmed: 11104619
Foley OW, Rauh-Hain JA, Clark RM, Goodman A, Growdon WB, Boruta DM, et al. Intraoperative Radiation Therapy in the management of gynecologic malignancies. Am J Clin Oncol. 2016;39(4):329–34.
doi: 10.1097/COC.0000000000000063
pubmed: 24685883
Delara R, Yang J, Suarez-Salvador E, Vora S, Magrina J, Butler K, et al. Radical extirpation with intraoperative Radiotherapy for locally recurrent Gynecologic Cancer: an institutional review. Mayo Clin Proc Innov Qual Outcomes. 2021;5(6):1081–8.
doi: 10.1016/j.mayocpiqo.2021.10.004
pubmed: 34841199
pmcid: 8606340
Hockel M. Long-term experience with (laterally) extended endopelvic resection (LEER) in relapsed pelvic malignancies. Curr Oncol Rep. 2015;17(3):435.
doi: 10.1007/s11912-014-0435-8
pubmed: 25687807
Calvo FA, Sole CV, Lozano MA, Gonzalez-Bayon L, Gonzalez-Sansegundo C, Alvarez A, et al. Intraoperative electron beam radiotherapy and extended surgical resection for gynecological pelvic recurrent malignancies with and without external beam radiation therapy: long-term outcomes. Gynecol Oncol. 2013;130(3):537–44.
doi: 10.1016/j.ygyno.2013.05.016
pubmed: 23707668
Dowdy SC, Mariani A, Cliby WA, Haddock MG, Petersen IA, Sim FH, et al. Radical pelvic resection and intraoperative radiation therapy for recurrent endometrial cancer: technique and analysis of outcomes. Gynecol Oncol. 2006;101(2):280–6.
doi: 10.1016/j.ygyno.2005.10.018
pubmed: 16321431
Garton GR, Gunderson LL, Webb MJ, Wilson TO, Cha SS, Podratz KC. Intraoperative radiation therapy in gynecologic cancer: update of the experience at a single institution. Int J Radiat Oncol Biol Phys. 1997;37(4):839–43.
doi: 10.1016/S0360-3016(96)00546-9
pubmed: 9128960
Barney BM, Petersen IA, Dowdy SC, Bakkum-Gamez JN, Klein KA, Haddock MG. Intraoperative Electron Beam Radiotherapy (IOERT) in the management of locally advanced or recurrent cervical cancer. Radiat Oncol. 2013;8:80.
doi: 10.1186/1748-717X-8-80
pubmed: 23566444
pmcid: 3641982
Martinez-Monge R, Jurado M, Aristu JJ, Moreno M, Cambeiro M, Perez-Ochoa A, et al. Intraoperative electron beam radiotherapy during radical surgery for locally advanced and recurrent cervical cancer. Gynecol Oncol. 2001;82(3):538–43.
doi: 10.1006/gyno.2001.6329
pubmed: 11520152
Tran PT, Su Z, Hara W, Husain A, Teng N, Kapp DS. Long-term survivors using intraoperative radiotherapy for recurrent gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2007;69(2):504–11.
doi: 10.1016/j.ijrobp.2007.03.021
pubmed: 17560736
Coelho TM, Fogaroli RC, Pellizzon ACA, De Castro DG, Gondim GRM, Silva MLG, et al. Intraoperative radiation therapy for the treatment of recurrent retroperitoneal and pelvic s: a single-institution analysis. Radiat Oncol. 2018;13(1):224.
doi: 10.1186/s13014-018-1168-x
pubmed: 30454036
pmcid: 6245634
Lambers K, Hasenburg A, Stickeler E, Gitsch G, Grosu AL, Henne K, et al. Customized treatment of recurrent gynaecological cancer–the need for intraoperative radiation therapy. Eur J Gynaecol Oncol. 2016;37(1):48–52.
pubmed: 27048109
Jablonska PA, Cambeiro M, Gimeno M, Aramendia JM, Minguez JA, Alcazar JL, et al. Intraoperative electron beam radiotherapy and perioperative high-dose-rate brachytherapy in previously irradiated oligorecurrent gynecological cancer: clinical outcome analysis. Clin Transl Oncol. 2021;23(9):1934–41.
doi: 10.1007/s12094-021-02601-0
pubmed: 33835408
Martinez-Monge R, Valtuena Peydro G, Cambeiro M, Aramendia JM, Gimeno M, Santisteban M, et al. Perioperative high-dose-rate brachytherapy in locally advanced and recurrent gynecological cancer: final results of a phase II trial. Brachytherapy. 2018;17(5):734–41.
doi: 10.1016/j.brachy.2018.04.007
pubmed: 29803537
Gemignani ML, Alektiar KM, Leitao M, Mychalczak B, Chi D, Venkatraman E, et al. Radical surgical resection and high-dose intraoperative radiation therapy (HDR-IORT) in patients with recurrent gynecologic cancers. Int J Radiat Oncol Biol Phys. 2001;50(3):687–94.
doi: 10.1016/S0360-3016(01)01507-3
pubmed: 11395237
Backes FJ, Billingsley CC, Martin DD, Tierney BJ, Eisenhauer EL, Cohn DE, et al. Does intra-operative radiation at the time of pelvic exenteration improve survival for patients with recurrent, previously irradiated cervical, vaginal, or vulvar cancer? Gynecol Oncol. 2014;135(1):95–9.
doi: 10.1016/j.ygyno.2014.07.093
pubmed: 25084510
Lv X, Rao H, Feng T, Wu C, Lou H. Whether individualized dose escalation should be recommended for lymph nodes with different sizes in the definitive radiotherapy of cervical cancer? Radiat Oncol. 2022;17(1):167.
doi: 10.1186/s13014-022-02132-0
pubmed: 36266716
pmcid: 9585835
Sole CV, Calvo FA, Lizarraga S, Gonzalez-Bayon L, Garcia-Sabrido JL. Intraoperative electron-beam radiation therapy with or without external-beam radiotherapy in the management of paraaortic lymph-node oligometastases from gynecological malignancies. Clin Transl Oncol. 2015;17(11):910–6.
doi: 10.1007/s12094-015-1326-7
pubmed: 26133521
Sole CV, Calvo FA, Lozano MA, Gonzalez-Bayon L, Gonzalez-Sansegundo C, Alvarez A, et al. External-beam radiation therapy after surgical resection and intraoperative electron-beam radiation therapy for oligorecurrent gynecological cancer. Long-term outcome. Strahlenther Onkol. 2014;190(2):171–80.
doi: 10.1007/s00066-013-0472-5
pubmed: 24306064
Liang M, Sheng L, Ke Y, Wu Z. The research progress on radiation resistance of cervical cancer. Front Oncol. 2024;14:1380448.
doi: 10.3389/fonc.2024.1380448
pubmed: 38651153
pmcid: 11033433
Onal C, Yuce Sari S, Yavas G, Oymak E, Birgi SD, Yigit E, et al. Outcome and safety analysis of endometrial cancer patients treated with postoperative 3D-conformal radiotherapy or intensity modulated radiotherapy. Acta Oncol. 2021;60(9):1154–60.
doi: 10.1080/0284186X.2021.1926537
pubmed: 33999750
Sprave T, Verma V, Forster R, Schlampp I, Bruckner T, Bostel T, et al. Radiation-induced acute toxicities after image-guided intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for patients with spinal metastases (IRON-1 trial): first results of a randomized controlled trial. Strahlenther Onkol. 2018;194(10):911–20.
doi: 10.1007/s00066-018-1333-z
pubmed: 29978307
Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novak Z, Black D, et al. Dostarlimab for Primary Advanced or recurrent endometrial Cancer. N Engl J Med. 2023;388(23):2145–58.
doi: 10.1056/NEJMoa2216334
pubmed: 36972026
Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J et al. Safety and anti activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. J Immunother Cancer. 2022;10(1).