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      High-dose-rate brachytherapy boost for locally advanced cervical cancer: Oncological outcome and toxicity analysis of 4 fractionation schemes

      research-article
      a , b , c , c , a , a , a , *
      Clinical and Translational Radiation Oncology
      Elsevier
      Cervical cancer, Brachytherapy, High-dose-rate, Fractionation scheme, BED, biologically effective dose, BID, twice-a-day, BMI, body-mass index, BT, brachytherapy, CT, computerized tomography, CTCAE, common terminology criteria for adverse events, CTV, clinical target volume, EBRT, external beam radiotherapy, EMBRACE, image guided intensity modulated External beam radiochemotherapy and MRI based Adaptative BRAchytherapy in locally advanced CErvical cancer , ESTRO, European Society for Radiotherapy and Oncology, EQD2Gy, equivalent dose at 2 Gy, FIGO, International Federation of Gynecology and Obstetrics, GEC, groupe européen de curiethérapie, GTV, gross tumor volume, HDR, high-dose-rate, HIV, human immunodeficiency virus, HR, high-risk, ICRU, International Commission on Radiation Units and measurements, IGABT, image-guided adaptative brachytherapy, IMRT, intensity modulated radiotherapy, IR, intermediate-risk, LACC, locally advanced cervical cancer, LDR, low-dose-rate, LFS, local recurrence-free survival, LQ, linear quadratic, MFU, median follow up, MFS, metastatic recurrence-free survival, MRI, magnetic resonance imaging, NA, not available, NCI, national cancer institute, NFS, nodal recurrence-free survival, OAR, organs at risk, OS, overall survival, OTT, overall treatment time, PDR, pulsed-dose-rate, PET, positron emission tomography, PFS, progression-free survival, pt, patient, pts, patients, PTV, planning target volume, RCT, radio-chemotherapy, SCC, squamous cell cancer, SEER, surveillance, epidemiology and end results

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          Highlights

          • Brachytherapy boost is a standard of care for locally advanced cervical cancer.

          • High-dose-rate brachytherapy (HDR-BT) boost procedure is not standardized.

          • The number of implants, fractions, doses and imaging differ in literature.

          • Bi-fractionated HDR-BT in 1 implant is feasible with good oncological outcome.

          • Bi-fractionated HDR-BT dose escalation slightly increases acute toxicity.

          Abstract

          Purpose

          Brachytherapy (BT) boost after radio-chemotherapy (RCT) is a standard of care in the management of locally advanced cervical cancer (LACC). As there is no consensus on high-dose-rate (HDR) BT fractionation schemes, our aim was to report the oncological outcome and toxicity profile of four different schemes using twice-a-day (BID) HDR-BT.

          Patients and methods

          This was an observational, retrospective, single institution study for patients with LACC receiving a HDR-BT boost. The latter was performed with a single implant and single imaging done on day 1. The different fractionation schemes were: 7 Gy + 4x3.5 Gy (group 1); 7 Gy + 4x4.5 Gy (group 2); 3x7Gy (group 3) and 3x8Gy (group 4). Local (LFS), nodal (NFS) and metastatic (MFS) recurrence-free survival as well as progression-free survival (PFS) and overall survival (OS) were analyzed. Acute (≤6 months) and late toxicities (>6 months) were reported.

          Results

          From 2007 to 2018, 191 patients were included. Median follow-up was 57 months [45–132] and median EQD2 10D 90CTV HR was 84, 82 and 90 Gy for groups 2, 3 and 4 respectively (dosimetric data missing for group 1). The 5-year LFS, NFS, MFS, PFS and OS were 85% [81–90], 83% [79–86], 70% [67–73], 61% [57–64] and 75% [69–78] respectively, with no significant difference between the groups. EQD2 10D 90CTV HR < 85 Gy was a prognostic factor for local recurrence in univariate analysis (p = 0.045). The rates of acute/late grade ≥ 2 urinary, digestive and gynecological toxicities were 9%/15%, 3%/15% and 9%/25% respectively.

          Conclusion

          Bi-fractionated HDR-BT boost seems feasible with good oncological outcome and slightly more toxicity after dose escalation.

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          Most cited references49

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          Cervical cancer

          Each year, more than half a million women are diagnosed with cervical cancer and the disease results in over 300 000 deaths worldwide. High-risk subtypes of the human papilloma virus (HPV) are the cause of the disease in most cases. The disease is largely preventable. Approximately 90% of cervical cancers occur in low-income and middle-income countries that lack organised screening and HPV vaccination programmes. In high-income countries, cervical cancer incidence and mortality have more than halved over the past 30 years since the introduction of formal screening programmes. Treatment depends on disease extent at diagnosis and locally available resources, and might involve radical hysterectomy or chemoradiation, or a combination of both. Conservative, fertility-preserving surgical procedures have become standard of care for women with low-risk, early-stage disease. Advances in radiotherapy technology, such as intensity-modulated radiotherapy, have resulted in less treatment-related toxicity for women with locally-advanced disease. For women with metastatic or recurrent disease, the overall prognosis remains poor; nevertheless, the incorporation of the anti-VEGF agent bevacizumab has been able to extend overall survival beyond 12 months. Preliminary results of novel immunotherapeutic approaches, similarly to other solid tumours, have shown promising results so far.
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            Cancer of the cervix uteri

            Since the publication of the last FIGO Cancer Report there have been giant strides in the global effort to reduce the burden of cervical cancer, with WHO announcing a call for elimination. In over 80 countries, including LMICs, HPV vaccination is now included in the national program. Screening has also seen major advances with implementation of HPV testing on a larger scale. However, these interventions will take a few years to show their impact. Meanwhile, over half a million new cases are added each year. Recent developments in imaging and increased use of minimally invasive surgery have changed the paradigm for management of these cases. The FIGO Gynecologic Oncology Committee has revised the staging system based on these advances. This chapter discusses the management of cervical cancer based on the stage of disease, including attention to palliation and quality of life issues.
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              Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology

              Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.
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                Author and article information

                Contributors
                Journal
                Clin Transl Radiat Oncol
                Clin Transl Radiat Oncol
                Clinical and Translational Radiation Oncology
                Elsevier
                2405-6308
                06 November 2021
                January 2022
                06 November 2021
                : 32
                : 15-23
                Affiliations
                [a ]Department of Radiation Oncology, Antoine Lacassagne Cancer Center, University of Côte d’Azur, 33 avenue Valombrose, 06189 Nice Cedex 2, Nice, France
                [b ]Department of Radiation Oncology, Pôle Santé République, Clermont-Ferrand, France
                [c ]Department of Statistics, Antoine Lacassagne Cancer Center, University of Côte d’Azur, Nice, France
                Author notes
                [* ]Corresponding author at: Department of Radiation Oncology, Antoine Lacassagne Cancer Center, University of Côte d’Azur, 33 Avenue Valombrose, 06189 Nice Cedex 2, Nice, France (J.-M. Hannoun-Levi). jean-michel.hannoun-levi@ 123456nice.unicancer.fr
                Article
                S2405-6308(21)00090-2
                10.1016/j.ctro.2021.10.005
                8592834
                9c507fcb-5cd1-482a-82f6-723608fbd62b
                © 2021 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 31 August 2021
                : 15 October 2021
                : 15 October 2021
                Categories
                Original Research Article

                cervical cancer,brachytherapy,high-dose-rate,fractionation scheme,bed, biologically effective dose,bid, twice-a-day,bmi, body-mass index,bt, brachytherapy,ct, computerized tomography,ctcae, common terminology criteria for adverse events,ctv, clinical target volume,ebrt, external beam radiotherapy,embrace, image guided intensity modulated external beam radiochemotherapy and mri based adaptative brachytherapy in locally advanced cervical cancer,estro, european society for radiotherapy and oncology,eqd2gy, equivalent dose at 2 gy,figo, international federation of gynecology and obstetrics,gec, groupe européen de curiethérapie,gtv, gross tumor volume,hdr, high-dose-rate,hiv, human immunodeficiency virus,hr, high-risk,icru, international commission on radiation units and measurements,igabt, image-guided adaptative brachytherapy,imrt, intensity modulated radiotherapy,ir, intermediate-risk,lacc, locally advanced cervical cancer,ldr, low-dose-rate,lfs, local recurrence-free survival,lq, linear quadratic,mfu, median follow up,mfs, metastatic recurrence-free survival,mri, magnetic resonance imaging,na, not available,nci, national cancer institute,nfs, nodal recurrence-free survival,oar, organs at risk,os, overall survival,ott, overall treatment time,pdr, pulsed-dose-rate,pet, positron emission tomography,pfs, progression-free survival,pt, patient,pts, patients,ptv, planning target volume,rct, radio-chemotherapy,scc, squamous cell cancer,seer, surveillance, epidemiology and end results
                cervical cancer, brachytherapy, high-dose-rate, fractionation scheme, bed, biologically effective dose, bid, twice-a-day, bmi, body-mass index, bt, brachytherapy, ct, computerized tomography, ctcae, common terminology criteria for adverse events, ctv, clinical target volume, ebrt, external beam radiotherapy, embrace, image guided intensity modulated external beam radiochemotherapy and mri based adaptative brachytherapy in locally advanced cervical cancer, estro, european society for radiotherapy and oncology, eqd2gy, equivalent dose at 2 gy, figo, international federation of gynecology and obstetrics, gec, groupe européen de curiethérapie, gtv, gross tumor volume, hdr, high-dose-rate, hiv, human immunodeficiency virus, hr, high-risk, icru, international commission on radiation units and measurements, igabt, image-guided adaptative brachytherapy, imrt, intensity modulated radiotherapy, ir, intermediate-risk, lacc, locally advanced cervical cancer, ldr, low-dose-rate, lfs, local recurrence-free survival, lq, linear quadratic, mfu, median follow up, mfs, metastatic recurrence-free survival, mri, magnetic resonance imaging, na, not available, nci, national cancer institute, nfs, nodal recurrence-free survival, oar, organs at risk, os, overall survival, ott, overall treatment time, pdr, pulsed-dose-rate, pet, positron emission tomography, pfs, progression-free survival, pt, patient, pts, patients, ptv, planning target volume, rct, radio-chemotherapy, scc, squamous cell cancer, seer, surveillance, epidemiology and end results

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