EMBRACE| Volume 127, ISSUE 3, P431-439, June 2018

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Bowel morbidity following radiochemotherapy and image-guided adaptive brachytherapy for cervical cancer: Physician- and patient reported outcome from the EMBRACE study



      This study describes late bowel morbidity prospectively assessed in the multi-institutional EMBRACE study on MRI-guided adaptive brachytherapy in locally advanced cervical cancer (LACC).


      A total of 1176 patients were analyzed. Physician reported morbidity (CTCAE v.3.0) and patient reported outcome (PRO) (EORTC QLQ C30/CX24) were assessed at baseline and at regular follow-up.


      At 3/5 years the actuarial incidence of bowel morbidity grade 3–4 was 5.0%/5.9%, including incidence of stenosis/stricture/fistula of 2.0%/2.6%. Grade 1–2 morbidity was pronounced with prevalence rates of 28–33% during follow-up. Diarrhea and flatulence were most frequently reported, significantly increased after 3 months and remained elevated during follow-up. Incontinence gradually worsened with time. PRO revealed high prevalence rates. Diarrhea ≥“a little” increased from 26% to 37% at baseline to 3 months and remained elevated, difficulty in controlling bowel increased from 11% to 26% at baseline to 3 months gradually worsening with time. Constipation and abdominal cramps improved after treatment.


      Bowel morbidity reported in this large cohort of LACC patients was limited regarding severe/life-threatening events. Mild-moderate diarrhea, flatulence and incontinence were prevalent after treatment with PROs indicating a considerable and clinically relevant burden. Critical knowledge based on the extent and manifestation pattern of treatment-related morbidity will serve future patient management.


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        • Pötter R.
        • Georg P.
        • Dimopoulos J.C.A.
        • et al.
        Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer.
        Radiother Oncol. 2011; 100: 116-123
        • Lindegaard J.C.
        • Fokdal L.U.
        • Nielsen S.K.
        • Juul-Christensen J.
        • Tanderup K.
        MRI-guided adaptive radiotherapy in locally advanced cervical cancer from a nordic perspective.
        Acta Oncol. 2013; 52: 1510-1519
        • Sturdza A.
        • Pötter R.
        • Fokdal L.U.
        • et al.
        Image guided brachytherapy in locally advanced cervical cancer: improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study.
        Radiother Oncol. 2016; 120: 428-433
        • Tanderup K.
        • Lindegaard J.C.
        • Kirisits C.
        • et al.
        Image guided adaptive brachytherapy in cervix cancer: a new paradigm changing clinical practice and outcome.
        Radiother Oncol. 2016; 120: 365-369
        • Lakosi F.
        • de Cuypere M.
        • Viet Nguyen P.
        • et al.
        Clinical efficacy and toxicity of radio-chemotherapy and magnetic resonance imaging-guided brachytherapy for locally advanced cervical cancer patients: a mono-institutional experience.
        Acta Oncol. 2015; 54: 1558-1566
        • Charra-Brunaud C.
        • Harter V.
        • Delannes M.
        • et al.
        Impact of 3D image-based PDR brachytherapy on outcome of patients treated for cervix carcinoma in France: results of the French STIC prospective study.
        Radiother Oncol. 2012; 103: 305-313
        • Nomden C.N.
        • De Leeuw A.A.C.
        • Roesink J.M.
        • et al.
        Clinical outcome and dosimetric parameters of chemo-radiation including MRI guided adaptive brachytherapy with tandem-ovoid applicators for cervical cancer patients: a single institution experience.
        Radiother Oncol. 2013; 107: 69-74
        • Rijkmans E.C.
        • Nout R.A.
        • Rutten I.H.H.M.
        • et al.
        Improved survival of patients with cervical cancer treated with image-guided brachytherapy compared with conventional brachytherapy.
        Gynecol Oncol. 2014; 135: 231-238
      1. EMBRACE (An international study on MRI-guided brachytherapy in locally advanced cervical cancer). <>.

        • Tan L.T.
        • Zahra M.
        Long-term survival and late toxicity after chemoradiotherapy for cervical cancer – The Addenbrooke’s experience.
        Clin Oncol. 2008; 20: 358-364
        • Kapp K.S.
        • Stuecklschweiger G.F.
        • Kapp D.S.
        • Poschauko J.
        • Pickel H.
        • Hackl A.
        Carcinoma of the cervix: analysis of complications after primary external beam radiation and Ir-192 HDR brachytherapy.
        Radiother Oncol. 1997; 42: 143-153
        • Gondi V.
        • Bentzen S.M.
        • Sklenar K.L.
        • et al.
        Severe late toxicities following concomitant chemoradiotherapy compared to radiotherapy alone in cervical cancer: an inter-era analysis.
        Int J Radiat Oncol Biol Phys. 2012; 84: 973-982
        • Vale C.L.
        • Tierney J.F.
        • Davidson S.E.
        • Drinkwater K.J.
        • Symonds P.
        Substantial improvement in UK cervical cancer survival with chemoradiotherapy: results of a Royal College of Radiologists’ Audit.
        Clin Oncol. 2010; 22: 590-601
        • Teo M.T.W.
        • Sebag-Montefiore D.
        • Donnellan C.F.
        Prevention and management of radiation-induced late gastrointestinal toxicity.
        Clin Oncol (R Coll Radiol). 2015; 27: 656-667
        • Kirchheiner K.
        • Nout R.A.
        • 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
        • Vale C.
        • Nightingale A.
        • Spera N.
        • Whelan A.
        • Hanley B.
        • Tierney J.F.
        Late complications from chemoradiotherapy for cervical cancer: reflections from cervical cancer survivors 10 years after the National Cancer Institute Alert.
        Clin Oncol. 2010; 22: 588-589
        • Davidson S.E.
        • Trotti A.
        • Ataman Ö.U.
        • et al.
        Improving the capture of adverse event data in clinical trials: the role of the International Atomic Energy Agency.
        Int J Radiat Oncol. 2007; 69: 1218-1221
        • Snyder C.F.
        • Blackford A.L.
        • Okuyama T.
        • et al.
        Using the EORTC-QLQ-C30 in clinical practice for patient management: identifying scores requiring a clinician’s attention.
        Qual Life Res. 2013; 22: 2685-2691
        • Snyder C.F.
        • Blackford A.L.
        • Aaronson N.K.
        • et al.
        Can patient-reported outcome measures identify cancer patients’ most bothersome issues?.
        J Clin Oncol. 2011; 29: 1216-1220
        • Trotti A.
        • Colevas A.D.
        • Setser A.
        • Basch E.
        Patient-reported outcomes and the evolution of adverse event reporting in oncology.
        J Clin Oncol. 2007; 25: 5121-5127
        • Andreyev H.J.N.
        Pelvic radiation disease.
        Color Dis. 2015; 17: 2-6
        • Mazeron R.
        • Fokdal L.U.
        • Kirchheiner K.
        • et al.
        Dose-volume effect relationships for late rectal morbidity in patients treated with chemoradiation and MRI-guided adaptive brachytherapy for locally advanced cervical cancer: results from the prospective multicentre EMBRACE study.
        Radiother Oncol. 2016; 120: 412-419
        • Haie-Meder C.
        • Pötter R.
        • Van Limbergen E.
        • et al.
        Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV.
        Radiother Oncol. 2005; 74: 235-245
        • Pötter R.
        • Haie-Meder C.
        • Van Limbergen E.
        • et al.
        Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy – 3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology.
        Radiother Oncol. 2006; 78: 67-77
        • Kirchheiner K.
        • Nout R.A.
        • Czajka-Pepl A.
        • et al.
        Health related quality of life and patient reported symptoms before and during definitive radio(chemo)therapy using image-guided adaptive brachytherapy for locally advanced cervical cancer and early recovery – a mono-institutional prospective study.
        Gynecol Oncol. 2015; 136: 415-423
        • Kirchheiner K.
        • Nout R.
        • Lindegaard J.
        • et al.
        Do clinicians and patients agree regarding symptoms? A comparison after definitive radiochemotherapy in 223 uterine cervical cancer patients.
        Strahlenther Onkol. 2012; 188: 933-939
        • Van De Poll-Franse L.V.
        • Mols F.
        • Gundy C.M.
        • et al.
        Normative data for the EORTC QLQ-C30 and EORTC-sexuality items in the general Dutch population.
        Eur J Cancer. 2011; 47: 667-675
        • Kirchheiner K.
        • Pötter R.
        • Tanderup K.
        • et al.
        Health-related quality of life in locally advanced cervical cancer patients after definitive chemoradiation therapy including image guided adaptive brachytherapy: an analysis from the EMBRACE study.
        Int J Radiat Oncol Biol Phys. 2016; 94: 1088-1098
        • Barker C.L.
        • Routledge J.A.
        • Farnell D.J.J.
        • Swindell R.
        • Davidson S.E.
        The impact of radiotherapy late effects on quality of life in gynaecological cancer patients.
        Br J Cancer. 2009; 100: 1558-1565
        • Klee M.
        • Thranov I.
        • Machin Prof D.
        The patients’ perspective on physical symptoms after radiotherapy for cervical cancer.
        Gynecol Oncol. 2000; 76: 14-23
        • Thanarajasingam G.
        • Hubbard J.M.
        • Sloan J.A.
        • et al.
        The imperative for a new approach to toxicity analysis in oncology clinical trials.
        J Natl Cancer Inst. 2015; 107: 1
        • Eifel P.J.
        • Levenback C.
        • Wharton J.T.
        • Oswald M.J.
        Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine cervix.
        Int J Radiat Oncol Biol Phys. 1995; 32: 1289-1300
        • Eifel P.J.
        • Winter K.
        • Morris M.
        • et al.
        Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of Radiation Therapy Oncology Group Trial (RTOG) 90–01.
        J Clin Oncol. 2004; 22: 872-880
        • Castelnau-Marchand P.
        • Chargari C.
        • Maroun P.
        • et al.
        Clinical outcomes of definitive chemoradiation followed by intracavitary pulsed-dose rate image-guided adaptive brachytherapy in locally advanced cervical cancer.
        Gynecol Oncol. 2015; 139: 288-294
        • Vistad I.
        • Cvancarova M.
        • Fosså S.D.
        • Kristensen G.B.
        Postradiotherapy morbidity in long-term survivors after locally advanced cervical cancer: how well do physicians’ assessments agree with those of their patients?.
        Int J Radiat Oncol Biol Phys. 2008; 71: 1335-1342
        • Di Maio M.
        • Gallo C.
        • Leighl N.B.
        • et al.
        Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials.
        J Clin Oncol. 2015; 33: 910-915
        • Dueck A.C.
        • Mendoza T.R.
        • Mitchell S.A.
        • et al.
        Validity and reliability of the U.S. National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).
        JAMA Oncol. 2015; 1: 1051-1059
        • Pötter R.
        • Tanderup K.
        • Kirisits C.
        • et al.
        The EMBRACE II study: The outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies.
        Clin Transl Radiat Oncol. 2018; 9: 48-60
        • Stacey R.
        • Green J.T.
        Radiation-induced small bowel disease: latest developments and clinical guidance.
        Ther Adv Chronic Dis. 2014; 5: 15-29
        • Thor M.
        • Olsson C.E.
        • Oh J.H.
        • et al.
        Relationships between dose to the gastro-intestinal tract and patient-reported symptom domains after radiotherapy for localized prostate cancer.
        Acta Oncol. 2015; 54: 1326-1334
        • Georg P.
        • Kirisits C.
        • Goldner G.
        • et al.
        Correlation of dose–volume parameters, endoscopic and clinical rectal side effects in cervix cancer patients treated with definitive radiotherapy including MRI-based brachytherapy.
        Radiother Oncol. 2009; 91: 173-180
        • Putta S.
        • Andreyev H.J.N.
        Overview faecal incontinence: a late side-effect of pelvic radiotherapy.
        YCLON. 2005; 17: 469-477
        • Andreyev H.J.N.
        • Muls A.C.
        • Norton C.
        • et al.
        Guidance: the practical management of the gastrointestinal symptoms of pelvic radiation disease.
        Frontline Gastroenterol. 2015; 6: 53-72
        • Andreyev H.J.N.
        • Benton B.E.
        • Lalji A.
        • et al.
        Algorithm-based management of patients with gastrointestinal symptoms in patients after pelvic radiation treatment (ORBIT): a randomised controlled trial.
        Lancet. 2013; 382: 2084-2092