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      Prolonged treatment planning can increase real rectal dose in 3D brachytherapy for cervical cancer

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          Abstract

          Purpose

          The purpose of this study was to evaluate the influence of 3D brachytherapy planning time on the real dose distribution.

          Material and methods

          10 patients with cervical cancer were evaluated using 2 computed tomography (CT) scans brachytherapy. The first scan was performed after the insertion of UVAG applicators, and the second was done after creating the treatment plan, just before the irradiation of first and third fraction. Both plans were compared in terms of changes of volumes and differences in the dose for high-risk organs using GEC-ESTRO Working Group parameters.

          Results

          The median planning time was 54 minutes (36-64 minutes). The absolute median change of volume for bladder, rectum, and sigmoid was 32.1 cm 3 (1.6-108.6 cm 3), 5.6 cm 3 (0.4-61.8 cm 3), and 8.4 cm 3 (0.2-74.1 cm 3), respectively. This difference led to an increased dose for bladder and sigmoid for D 0.1cc by 46.7 cGy and 25.7 cGy, for D 1cc by 59.2 cGy and 11.8 cGy, and for D 2cc by 44.7 cGy and 10 cGy, respectively, per each fraction. Measured volume change in case of rectum led to a decreased dose per each fraction for D 0.1cc with 7.1 cGy, for D 1cc with 3.5 cGy, and for D 2cc with 4.8 cGy. We observed that statistically significant dependency between the planning time and the dose was proved for rectum. The longer time for planning, the higher dose for rectum. The correlation coefficient for D 0.1cc was 0.6715 ( p = 0.0061), for D 1cc was 0.6404 ( p = 0.011), and for D 2cc was 0.5891 ( p = 0.0197).

          Conclusions

          Extended treatment planning time for brachytherapy due to the changes in topography of small pelvis can lead to different dose in high-risk organs than previously planned. It seems that the most significant changes are related to rectum.

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          Most cited references 15

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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

          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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            Clinical impact of MRI assisted dose volume adaptation and dose escalation in brachytherapy of locally advanced cervix cancer.

            To investigate the clinical impact of MRI based cervix cancer brachytherapy combined with external beam radiochemotherapy applying dose volume adaptation and dose escalation in a consecutive group of patients with locally advanced cervix cancer. In the period 1998-2003, 145 patients with cervix cancer stages IB-IVA were treated with definitive radiotherapy +/- cisplatin chemotherapy. Median age was 60 years. In 67 patients, the tumour size was 2-5 cm, in 78 patients it was >5 cm. In 29 cases the standard intracavitary technique was combined with interstitial brachytherapy. Total prescribed dose was 80-85 Gy (total biologically equivalent dose in 2 Gy fractions). Since 2001, MRI based treatment planning integrated systematic concepts for High Risk Clinical Target Volume (HR CTV) and organs at risk (OAR), biological modelling, Dose-Volume-Histogram analysis, dose-volume-adaptation (D90, D 2 cm(3)), and dose escalation, if appropriate and feasible. Dose volume adaptation was performed in 130/145 patients. The mean D90 during the whole period was 86 Gy, with a mean D90 of 81 Gy and 90 Gy during the first and second period, respectively (p 5 cm it was 71% in 1998-2000 and 90% in 2001-2003 (p=0.05). Progression free survival (PFS) for true pelvis (local control) was 85%, PFS for distant metastases was 80%, both at 3 years. Local control for tumours >5 cm was 64% in 1998-2000 and 82% in 2001-2003 (p=0.09) and 100% and 96%, respectively, for tumours 2-5 cm. PFS for distant metastases remained the same during the two treatment periods with 79% and 80%. Overall survival (OS) was 58%, and cancer-specific survival (CSS) was 68% at 3 years. In the two different periods improvement in OS was from 53% to 64% (p=0.03) and in CSS from 62% to 74% (p=0.13). Improvement occurred only in tumours >5 cm: OS 28% versus 58% (p=0.003); CSS 40% versus 62% (p=0.07). Actuarial late morbidity rate (LENT SOMA, grades 3 and 4) at 3 years was gastrointestinal 4%, urinary 4% and vaginal 5% (stage IIA/IIIA). Gastrointestinal and urinary late morbidity (G3,G4) was 10% in 1998-2000 and 2% in 2001-2003. In locally advanced extensive cervix cancer, local control of > or = 85% can be achieved with low treatment related morbidity (G3/G4), when exploiting the potential of MRI based 3D treatment planning including dose volume adaptation and dose escalation and a combined intracavitary/interstitial brachytherapy, if appropriate. A significant impact of this improvement of local control on survival is to be expected. For locally advanced limited disease the MRI based approach will likely result in assuring excellent local control (> or = 95%) and in minimizing treatment related morbidity.
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              MRI-guided adaptive radiotherapy in locally advanced cervical cancer from a Nordic perspective.

              The first Nordic protocol for three-dimensional (3D) planned radiotherapy in locally advanced cervical cancer was the prospective NOCECA study (1994-2000). NOCECA consisted of computed tomography (CT)-based 3D conformal external beam radiotherapy (EBRT) with a simultaneous integrated boost (SIB) to the primary tumour combined with brachytherapy (BT) based on x-ray imaging. In NOCECA the planning aim was to achieve 80 Gy at point A from EBRT and BT combined. However, the balance of dose between EBRT and BT was determined by tumour size at diagnosis with more EBRT dose given to point A and less by BT in more advanced stages. In 2005 image-guided adaptive brachytherapy (IGABT) based on magnetic resonance imaging (MRI) and optimisation of the BT dose distribution to the remaining tumour and cervix at time of BT (HR CTV) was introduced in Aarhus. EBRT remained like in NOCECA until 2008 when the SIB to the primary tumour was abandoned and IMRT was introduced as routine technique. In this study, we report outcome of our first five-year experience with IGABT using our NOCECA cohort as reference.
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                Author and article information

                Journal
                J Contemp Brachytherapy
                J Contemp Brachytherapy
                JCB
                Journal of Contemporary Brachytherapy
                Termedia Publishing House
                1689-832X
                2081-2841
                30 April 2020
                April 2020
                : 12
                : 2
                : 118-123
                Affiliations
                [1 ]Department of Oncology, Palacký University Medical School & Teaching Hospital, Olomouc, Czech Republic,
                [2 ]Faculty of Medicine, Palacký University Olomouc, Olomouc, Czech Republic,
                [3 ]First Faculty of Medicine, Charles University, Prague, Czech Republic,
                [4 ]Comprehensive Cancer Centre, Novy Jicin, Czech Republic,
                [5 ]Comprehensive Cancer Centre Multiscan, Pardubice, Czech Republic
                Author notes
                Address for correspondence: Martin Dolezel, PhD, Ass. Prof., Department of Oncology, Palacký University Medical School & Teaching Hospital, I.P. Pavlova 6, Olomouc 775 20, Czech Republic, phone: +420 588 444 295, e-mail: dolezelm@ 123456email.cz
                Article
                40409
                10.5114/jcb.2020.94580
                7207232
                Copyright © 2020 Termedia

                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/)

                Categories
                Original Paper

                Oncology & Radiotherapy

                cervical cancer, 3d brachytherapy, treatment planning

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