eISSN: 2081-2841
ISSN: 1689-832X
Journal of Contemporary Brachytherapy
Current Issue Archive Supplements Articles in Press Journal Information Aims and Scope Editorial Office Editorial Board Register as Author Register as Reviewer Instructions for Authors Abstracting and indexing Subscription Advertising Information Links
SCImago Journal & Country Rank

vol. 10
Review paper

Vaginal toxicity after high-dose-rate endovaginal brachytherapy: 20 years of results

Durim Delishaj, Amelia Barcellini, Romerai D’Amico, Stefano Ursino, Francesco Pasqualetti, Ilaria Costanza Fumagalli, Carlo Pietro Soatti

J Contemp Brachytherapy 2018; 10, 6: 559–566
Online publish date: 2018/11/18
View full text
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero
To evaluate vaginal toxicity (primary endpoint) and local control (secondary endpoint) in patients with endometrial cancer who underwent primary surgery and adjuvant high-dose-rate (HDR) endovaginal brachytherapy (BT).

Material and methods
In September 2017, the authors conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus, and Cochrane library. In this systematic review, the authors included randomized trials, non-randomized trials, prospective studies, retrospective studies, and cases. The time period of the research included articles published from September 1997 to September 2017.

Acute endovaginal toxicity occurred in less than 20.6% and all acute toxicities were G1-G2. The most common early side effects due to HDR-BT treatment were vaginal inflammation, vaginal irritation, dryness, discharge, soreness, swelling, and fungal infection. G1-G2 late toxicity occurred in less than 27.7%. Finally, G3-G4 late vaginal occurred in less than 2%. The most common late side effects consisted of vaginal discharge, dryness, itching, bleeding, fibrosis, telangiectasias, stenosis, short or narrow vagina, and dyspareunia.

The data suggest that HDR endovaginal brachytherapy, with or without chemotherapy, is very well tolerated with low rates of acute and late vaginal toxicities. Further prospective studies with higher numbers of patients and longer follow-up are necessary to evaluate acute and late toxicities after HDR endovaginal brachytherapy.


brachytherapy, endometrial cancer, HDR vaginal brachytherapy, radiotherapy

Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67: 7-30.
Nout RA, Putter H, Jürgenliemk-Schulz IM et al. Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: First results of the randomized PORTEC-2 trial. J Clin Oncol 2009; 27: 3547-3556.
Cowles TA, Magrina JF, Masterson BJ, Capen CV. Comparison of clinical and surgical-staging in patients with endometrial carcinoma. Obstet Gynecol 1985; 66: 413-416.
Burke WM, Orr J, Leitao M et al. SGO Clinical Practice Endometrial Cancer Working Group, Society of Gynecologic Oncology Clinical Practice Committee. Endometrial cancer: a review and current management strategies: part I. Gynecol Oncol 2014; 134: 385-392.
Johnson N, Cornes P. Survival and recurrent disease after postoperative radiotherapy for early endometrial cancer: systematic review and meta-analysis. BJOG 2007; 114: 1313-1320.
Nout R, Smit V, Putter H et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet 2010; 375: 816-823.
MacLeod C, Fowler A, Duval P et al. High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer. Int J Radiat Oncol Biol Phys 1998; 42: 1033-1039.
Sorbe B, Straumits A, Karlsso L. Intravaginal high-dose-rate brachytherapy for Stage I endometrial cancer: A randomized study of two dose-per-fraction levels. Int J Radiat Oncol Biol Phys 2005; 62: 1385-1389.
Sorbe B, Straumits A, Karlsso L. Intravaginal high-dose-rate brachytherapy for Stage I endometrial cancer: A randomized study of two dose-per-fraction levels. Int J Gynecol Cancer 2009; 19: 873-878.
Chong I, Hoskin PJ. Vaginal vault brachytherapy as sole postoperative treatment for low-risk endometrial cancer. Brachytherapy 2008; 7: 195-199.
Colombo N, Creutzberg C, Amant F et al. ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: Diagnosis, treatment and follow-up. Radiother Oncol 2015; 117: 559-581.
Alektiar KM, McKee A, Venkatraman E et al. Intravaginal high dose rate brachytherapy for Stage IB (FIGO Grade 1, 2)
endometrial cancer. Int J Radiat Oncol Biol Phys 2002; 53: 707-713.
Anderson JM, Stea B, Hallum AV et al. High-dose-rate postoperative vaginal cuff irradiation alone for Stage IB, and IC endometrial cancer. Int J Radiat Oncol Biol Phys 2000; 46: 417-425.
Onsrud M, Strickert T, Marthinsen AB. Late reactions after postoperative high-dose-rate intravaginal brachytherapy for endometrial cancer: a comparison of standardized and individualized target volumes. Int J Radiat Oncol Biol Phys 2001; 49: 749-755.
Lin LL, Mutch DG, Rader JS et al. External radiotherapy versus vaginal brachytherapy for patients with intermediate risk endometrial cancer. Gynecol Oncol 2007; 106: 215-220.
LENT SOMA scales for all anatomic sites. Int J Radiat Oncol Biol Phys 1995; 31: 1049-1091.
Chassagne D, Sismondi P, Horiot JC et al. A glossary for reporting complications of treatment in gynecological cancers. Radiother Oncol 1993; 26: 195-202.
Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995; 31: 1341-1346.
CTCAE v. 4.0. NIH Publication No. 09-5410.
Katz A, Njuguna E, Rakowsky E et al. Early development of vaginal shortening during radiation therapy for endometrial or cervical cancer. Int J Gynecol Cancer 2001; 11: 234-235.
Abitbol MM, Davenport JH. The irradiated vagina. Obstetr Gynecol 1974; 44: 249-256.
Grigsby FW, Russell A, Bruner D et al. Late injury of cancer therapy on the female reproductive tract. Int J Radiat Oncol Biol Phys 1995; 31: 1281-1299.
Brand AH, Bull CA, Cakir B. Vaginal stenosis in patients treated with radiotherapy for carcinoma of the cervix. Int
J Radiat Oncol Biol Phys 2006; 16: 288-293.
Decruze SB, Guthrie D, Magnani R. Prevention of vaginal stenosis in patients following vaginal brachytherapy. Clin Oncol 1999; 11: 46-48.
Jackson S, James M, Abrams P. The effect of oestradiol on vaginal collagen metabolism in postmenopausal women with genuine stress incontinence. BJOG 2002; 109: 339-344.
Pitkin RM, Bradbury JT. The effects of topical estrogen on irradiated vaginal epithelium. Am J Obstet Gynecol 1965; 15: 175-182.
Qian JM, Stahl JM, Young MR et al. Impact of vaginal cylinder diameter on outcomes following brachytherapy at for early stage endometrial cancer. J Gynecol Oncol 2017; 28: e84.
Wolf JK. Prevention and treatment of vaginal stenosis resulting from pelvic radiation therapy. Commun Oncol 2006; 3: 665-671.
Bertelson K. Sexual dysfunction after treatment of cervical cancer. Danish Med Bull 1983; 30: 31-34.
Kirchheiner K, Nout RA, Tanderup K et al. Manifestation pattern of early-late vaginal morbidity after definitive radiation (chemo)therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer: an analysis from the EMBRACE study. Int J Radiat Oncol Biol Phys 2014; 89: 88-95.
Oyekunle EO, Obed RI, Akinlade B, Ntekim A. Comparison of doses to the rectum derived from treatment planning system with in-vivo dose values in vaginal vault brachytherapy using cylinder applicators. J Contemp Brachytherapy 2015; 7: 485-491.
Hassouna A, Bahadur YA, Constantinescu C et al. Assessment of air pockets in high-dose-rate vaginal cuff brachytherapy using cylindrical applicators. J Contemp Brachytherapy 2014; 6: 271-275.
KirchheinerK, Nout RA, Lindegaard JC et al. Dose-effect relationship and risk factors for vaginal stenosis after definitive radio(chemo)therapy with image-guided brachytherapy for locally advanced cervical cancer in the EMBRACE study. Radiother Oncol 2016; 118: 160-166.
Greven K, Winter K, Underhill K et al. Radiation Therapy Oncology Group. Preliminary analysis of RTOG 9708: Adjuvant postoperative radiotherapy combined with cisplatin/paclitaxel chemotherapy after surgery for patients with high-risk endometrial cancer. Int J Radiat Oncol Biol Phys 2004; 59: 168-173.
Ríos I, Rovirosa A, Ascaso C et al. Vaginal-cuff control and toxicity results of a daily HDR brachytherapy schedule in endometrial cancer patients. Clin Transl Oncol 2016; 18: 925-930.
De Boer SM, Nout RA, Jürgenliemk-Schulz IM et al. Long-term impact of endometrial cancer diagnosis and treatment on health-related quality of life and cancer survivorship: results from the randomized PORTEC-2 Trial. Int J Radiat Oncol Biol Phys 2015; 93: 797-809.
Landrum LM, Nugent EK, Zuna RE et al. Phase II trial of vaginal cuff brachytherapy followed by chemotherapy in early stage endometrial cancer patients with high-intermediate risk factors. Gynecol Oncol 2014; 132: 50-54.
Rovirosa A, Valduvieco I, Ascaso C et al. Daily schedule for high-dose-rate brachytherapy in postoperative treatment of endometrial carcinoma. Clin Transl Oncol 2013; 15: 111-116.
Hong JJ, Yacoub SF, Blevins JC et al. El-Mahdi AM. High dose rate vaginal brachytherapy in early stage endometrial carcinoma: preliminary analysis. Am J Clin Oncol 1997; 20: 254-258.
Weiss E, Hirnle P, Arnold-Bofinger H et al. Adjuvant vaginal high-dose-rate afterloading alone in endometrial carcinoma: patterns of relapse and side effects following low-dose therapy. Gynecol Oncol 1998; 71: 72-76.
Chadha M, Nanavati PJ, Liu P et al. Patterns of failure in endometrial carcinoma stage IB grade 3 and IC patients treated with postoperative vaginal vault brachytherapy. Gynecol Oncol 1999; 75: 103-107.
Horowitz NS, Peters WA, Smith MR et al. Adjuvant high dose rate vaginal brachytherapy as treatment of stage I and II endometrial carcinoma. Obstet Gynecol 2002; 99: 235-240.
Park HS, Ratner ES, Lucarelli L et al. Predictors of vaginal stenosis after intravaginal high-dose-rate brachytherapy for endometrial carcinoma. Brachytherapy 2015; 14: 464-470.
Damast S, Higgins S, Ratner E et al. High-dose-rate vaginal brachytherapy with chemotherapy for surgically staged localized uterine serous carcinoma. J Contemp Brachytherapy 2015; 7: 35-40.
Eldredge-Hindy HB, Eastwick G, Anne PR et al. Adjuvant vaginal cuff brachytherapy for high-risk, early stage endometrial cancer. J Contemp Brachytherapy 2014; 6: 262-270.
Eltabbakh, GH, Piver MS, Hempling RE, Shin KH. 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. Int J Radiat Oncol Biol Phys 1997; 38: 373-380.
Nunns D, Williamson K, Swaney L, Davy M. The morbidity of surgery and adjuvant radiotherapy in the management of endometrial carcinoma. Int J Gynecol Cancer 2000; 10: 233-238.
Fanning J, Nanavati PJ, Hilgers RD et al. Surgical staging and high dose rate brachytherapy for endometrial cancer: limiting external radiotherapy to node-positive tumors. Obstet Gynecol 1996; 87: 1041-1044.
Kellas-Ślęczka S, Wojcieszek P, Białas B et al. Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer. J Contemp Brachytherapy 2012; 4: 247-252.
Schover LR, Fife M, Gershenson DM et al. Sexual dysfunction and treatment for early stage cervical cancer. Cancer 2006; 63: 204-212.
Laliscia C, Fabrini MG, Delishaj D et al. Clinical outcomes of stereotactic body radiotherapy in oligometastatic gynecological cancer. Int J Gynecol Cancer 2017; 27: 396-402.
Laliscia C, Fabrini MG, Delishaj D et al. Concomitant external-beam irradiation and chemotherapy followed by high-dose rate brachytherapy boost in the treatment of squamous cell carcinoma of the vagina: a single-center retrospective study. Anticancer Res 2016; 36: 1885-1889.
Gerdin B, Hallgren R. Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation. J Intern Med 1997; 242: 49-55.
Markowska J, Madry R, Markowska A et al. The effect of hyaluronic acid (Cicatridine) on healing and regeneration of the uterine cervix and vagina and vulvar dystrophy therapy. Eur J Gynaecol Oncol 2011; 32: 65-68.
Dinicola S, Pasta V, Costantino D et al. Hyaluronic acid and vitamins are effective in reducing vaginal atrophy in women receiving radiotherapy. Minerva Ginecol 2015; 67: 523-531.
Laliscia C, Delishaj D, Fabrini MG et al. Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit? J Contemp Brachytherapy 2016; 8: 512-517.
American College of Obstetricians and Gynecologists. ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August 2005: management of endometrial cancer. Obstet Gynecol 2005; 106: 413-425.
Petereit DG, Tannehill SP, Grosen EA et al. Outpatient vaginal cuff brachytherapy for endometrial cancer. Int J Radiat Oncol Biol Phys 1999; 9: 456-462.
Creutzberg CL, Van-Putten WL, Koper PC et al. Surgery and postoperative radiotherapy versus surgery alone for patients with Stage-1 endometrial carcinoma: Multicentre randomized trial. Lancet 2000; 355: 1404-1411.
Kong A, Johnson N, Kitchener HC, Lawrie TA. Adjuvant radiotherapy for stage I endometrial cancer: an updated Cochrane systematic review and meta-analysis. J Natl Cancer Inst 2012; 104: 1625-1634.
Draghini L, Maranzano E, Casale M et al. Definitive three-dimensional high-dose-rate brachytherapy for inoperable endometrial cancer. J Contemp Brachytherapy 2017; 9: 118-123.
Ozdemir Y, Dolek Y, Onal C. Effects of vaginal cylinder position on dose distribution in patients with endometrial carcinoma in treatment of vaginal cuff brachytherapy. J Contemp Brachytherapy 2017; 9: 230-235.
Sunil RA, Bhavsar D, Shruthi MN et al. Combined external beam radiotherapy and vaginal brachytherapy versus vaginal brachytherapy in stage I, intermediate- and high-risk cases of endometrium carcinoma. J Contemp Brachytherapy 2018; 10: 105-114.
Sekii S, Murakami N, Kato T et al. Outcomes of salvage high-dose-rate brachytherapy with or without external beam radiotherapy for isolated vaginal recurrence of endometrial cancer. J Contemp Brachytherapy 2017; 9: 209-215.
Autorino R, Tagliaferri L, Campitelli M et al. EROS study: evaluation between high-dose-rate and low-dose-rate vaginal interventional radiotherapy (brachytherapy) in terms of overall survival and rate of stenosis. J Contemp Brachytherapy 2018; 10: 315-320.
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe