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      Predictive value of Excel forms based on an automatic calculation of dose equivalent in 2 Gy per fraction in adaptive brachytherapy for cervical cancer

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          Abstract

          Purpose

          External beam radiotherapy (EBRT) combined with brachytherapy (BT) is the standard mode of radical radiotherapy for locally advanced cervical cancer. The cumulative equivalent doses in 2 Gy per fraction (EQD 2) is an important basis for estimating the probability of local control of tumors and monitoring the occurrence of side effects in normal tissues. The purpose of this study was to explore the predictive value of Excel forms based on an automatic calculation in radical adaptive BT for cervical cancer.

          Material and methods

          A retrospective analysis of 119 patients suffering from cervical cancer, treated with radical radiotherapy. All patients were treated with EBRT and adaptive BT. EBRT prescribed dose was 42.0-50.4 Gy in 21-28 fractions. BT nominal prescribed dose was 28 Gy in 4 fractions, separated by one week. Total EQD 2 prediction at nth ( n = 1-3) BT (TEPB n) or actual cumulative EQD 2 (ACEQD 2) can be calculated automatically by inputting the physical dose based on an in-house designed application. The relationship between TEPB n and ACEQD 2 was evaluated, and the predictive value of Excel forms based on the automatic calculation was analyzed.

          Results

          For the volume of high-risk clinical target, there was a significant decrease between BT1 and BT2. Similarly, for the volume of intermediate-risk clinical target, there was a significant decrease between BT2 and BT3. The sensitivity ranges of TEPB 1, TEPB 2, and TEPB 3 prediction were 74.5-91.3%, 83.7-95.7%, and 92.9-99.1%, respectively, and the specificity ranges were 46.7-80.0%, 53.3-90.5%, and 66.7-90.5%, respectively.

          Conclusions

          The in-house designed application has the function of quickly reading dose-volume histogram (DVH) parameters from the treatment planning system, which allows for balance between the total dose to target volumes and organs at risk (OARs). Excel forms based on EQD 2 automatic calculation presents high predictive accuracy.

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          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

          Richard Pötter, Petra Georg, Johannes Dimopoulos … (2011)
          Background To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT) ± chemotherapy (ChT). Methods Treatment schedule was EBRT with 45–50.4 Gy ± concomitant cisplatin chemotherapy plus 4 × 7 Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90 > 85 Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75 Gy for rectum and sigmoid and 90 Gy for bladder. Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis. Findings One hundred and fifty-six consecutive patients (median age 58 years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5 cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42 months for all patients. Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93 ± 13 Gy, D2cc 86 ± 17 Gy for bladder, 65 ± 9 Gy for rectum and 64 ± 9 Gy for sigmoid. Complete remission was achieved in 151/156 patients (97%). Overall local control at 3 years was 95%; 98% for tumours 2–5 cm, and 92% for tumours >5 cm (p = 0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3 years was overall 74%, 83% for tumours 2–5 cm, 70% for tumours >5 cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3 years was in total 68%, 72% for tumours 2–5 cm, 65% for tumours >5 cm, 74% for IB, 78% for IIB, 45% for IIIB. In regard to late morbidity in total 188 grade 1 + 2 and 11 grade 3 + 4 late events were observed in 143 patients. G1 + 2/G3 + 4 events for bladder were n = 32/3, for rectum n = 14/5, for bowel (including sigmoid) n = 3/0, for vagina n = 128/2, respectively. Interpretation 3D conformal radiotherapy ± chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95–100% at 3 years in limited/favourable (IB/IIB) and 85–90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65–70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings.
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            The EMBRACE II study: The outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies

            Richard Pötter, Kari Tanderup, Christian Kirisits … (2018)
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              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.

              Richard Pötter, Christine Haie-Meder, Erik van Limbergen … (2006)
              The second part of the GYN GEC ESTRO working group recommendations is focused on 3D dose-volume parameters for brachytherapy of cervical carcinoma. Methods and parameters have been developed and validated from dosimetric, imaging and clinical experience from different institutions (University of Vienna, IGR Paris, University of Leuven). Cumulative dose volume histograms (DVH) are recommended for evaluation of the complex dose heterogeneity. DVH parameters for GTV, HR CTV and IR CTV are the minimum dose delivered to 90 and 100% of the respective volume: D90, D100. The volume, which is enclosed by 150 or 200% of the prescribed dose (V150, V200), is recommended for overall assessment of high dose volumes. V100 is recommended for quality assessment only within a given treatment schedule. For Organs at Risk (OAR) the minimum dose in the most irradiated tissue volume is recommended for reporting: 0.1, 1, and 2 cm3; optional 5 and 10 cm3. Underlying assumptions are: full dose of external beam therapy in the volume of interest, identical location during fractionated brachytherapy, contiguous volumes and contouring of organ walls for >2 cm3. Dose values are reported as absorbed dose and also taking into account different dose rates. The linear-quadratic radiobiological model-equivalent dose (EQD2)-is applied for brachytherapy and is also used for calculating dose from external beam therapy. This formalism allows systematic assessment within one patient, one centre and comparison between different centres with analysis of dose volume relations for GTV, CTV, and OAR. Recommendations for the transition period from traditional to 3D image-based cervix cancer brachytherapy are formulated. Supplementary data (available in the electronic version of this paper) deals with aspects of 3D imaging, radiation physics, radiation biology, dose at reference points and dimensions and volumes for the GTV and CTV (adding to [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]). It is expected that the therapeutic ratio including target coverage and sparing of organs at risk can be significantly improved, if radiation dose is prescribed to a 3D image-based CTV taking into account dose volume constraints for OAR. However, prospective use of these recommendations in the clinical context is warranted, to further explore and develop the potential of 3D image-based cervix cancer brachytherapy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Contemp Brachytherapy
                Journal ID (iso-abbrev): J Contemp Brachytherapy
                Journal ID (publisher-id): JCB
                Title: Journal of Contemporary Brachytherapy
                Publisher: Termedia Publishing House
                ISSN (Print): 1689-832X
                ISSN (Electronic): 2081-2841
                Publication date (Electronic): 30 October 2020
                Publication date (Print): October 2020
                Volume: 12
                Issue: 5
                Pages: 454-461
                Affiliations
                [1 ]Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun, China,
                [2 ]Department of Radiation Oncology, Jilin City Hospital of Chemical Industry, Jilin, China
                Author notes
                Address for correspondence: Hongfu Zhao, MS, Department of Radiation Oncology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, 130033 Changchun, China, phone: +86 135 0432 8263, fax: +86 431 84995511, ) e-mail: zhaohf@ 123456jlu.edu.cn

                Guanghui Cheng, Xin Mu, Ying Liu contributed equally to this work.

                Article
                Publisher ID: 42246
                DOI: 10.5114/jcb.2020.100378
                PMC ID: 7701924
                SO-VID: cb98a69c-99f2-41df-b7dc-ca70cdf96bf2
                Copyright © Copyright © 2020 Termedia
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY -NC -SA 4.0). License ( http://creativecommons.org/licenses/by-nc-sa/4.0/).

                History
                Date received : 21 December 2019
                Date accepted : 02 August 2020
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cervical cancer,high-dose-rate,adaptive brachytherapy,eqd2,dose prediction
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cervical cancer, high-dose-rate, adaptive brachytherapy, eqd2, dose prediction

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