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      Impact of different dose prescription schedules on EQD 2 in high-dose-rate intracavitary brachytherapy of carcinoma cervix

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          Abstract

          Purpose

          To observe the effect of different high-dose-rate (HDR) intracavitary brachytherapy dose schedules on equieffective dose in 2 Gy per fraction (EQD 2).

          Material and methods

          It is a retrospective study involving 50 cervical cancer patients, who received external radiotherapy of 45 Gy in 25 fractions and underwent intracavitary brachytherapy (ICBT). Computed tomography (CT) simulation was done after insertion of the applicators. High-risk clinical target volume (CTVHR) and organs at risk (OARs) such as bladder, rectum, and sigmoid were contoured. Four different plans were generated for each patient, with dose prescriptions of 5.5 Gy × 5 fractions (plan A), 6.5 Gy × 4 fractions (plan B), 7 Gy × 4 fractions (plan C), and 9 Gy × 2 fractions (plan D), delivered to CTV HR. The total EQD 2 for 0.1 cm 3 and 2 cm 3 of bladder, rectum, and sigmoid as well as dose received by 90% of the CTV HR (D 90) and point A were calculated. The values were analyzed and compared with available literature.

          Results

          The mean CTV HR volume was 47.12 ±13.8 cm 3. All plans delivered similar EQD 2 for 0.1 cm 3 and 2 cm 3 of sigmoid. Plan D delivered lesser EQD 2 compared to other plans for bladder, rectum, D 90 CTVHR, and point A ( p = 0.0001). Plan C delivered higher EQD 2 to OARs compared to other plans ( p = 0.001). Plan A, B, and plan C delivered similar EQD 2 for D 90 CTV HR and point A.

          Conclusions

          EQD 2 of bladder, rectum, sigmoid, D 90 CTV HR, and point A were similar with 5.5 Gy × 5 fractions, 6.5 Gy × 4 fractions, and 7 Gy × 4 fractions, whereas EQD 2 of 9 Gy × 2 fractions was significantly unfavorable compared to other schedules. Further clinical studies are recommended to observe clinical outcomes.

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          Most cited references 19

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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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            Computed tomography versus magnetic resonance imaging-based contouring in cervical cancer brachytherapy: results of a prospective trial and preliminary guidelines for standardized contours.

            To compare the contours and dose-volume histograms (DVH) of the tumor and organs at risk (OAR) with computed tomography (CT) vs. magnetic resonance imaging (MRI) in cervical cancer brachytherapy. Ten patients underwent both MRI and CT after applicator insertion. The dose received by at least 90% of the volume (D(90)), the minimal target dose (D(100)), the volume treated to the prescription dose or greater for tumor for the high-risk (HR) and intermediate-risk (IR) clinical target volume (CTV) and the dose to 0.1 cm3, 1 cm3, and 2 cm3 for the OARs were evaluated. A standardized approach to contouring on CT (CT(Std)) was developed, implemented (HR- and IR-CTV(CTStd)), and compared with the MRI contours. Tumor height, thickness, and total volume measurements, as determined by either CT or CT(Std) were not significantly different compared with the MRI volumes. In contrast, the width measurements differed in HR-CTV(CTStd) (p = 0.05) and IR-CTV(CTStd) (p = 0.01). For the HR-CTV(CTStd), this resulted in statistically significant differences in the volume treated to the prescription dose or greater (MRI, 96% vs. CT(Std), 86%, p = 0.01), D(100) (MRI, 5.4 vs. CT(Std), 3.4, p <0.01), and D(90) (MRI, 8.7 vs. CT(Std), 6.7, p <0.01). Correspondingly, the IR-CTV DVH values on MRI vs. CT(Std), differed in the D(100) (MRI, 3.0 vs. CT(Std), 2.2, p = 0.01) and D(90) (MRI, 5.6 vs. CT(Std), 4.6, p = 0.02). The MRI and CT DVH values of the dose to 0.1 cm3, 1 cm3, and 2 cm3 for the OARs were similar. Computed tomography-based or MRI-based scans at brachytherapy are adequate for OAR DVH analysis. However, CT tumor contours can significantly overestimate the tumor width, resulting in significant differences in the D(90), D(100), and volume treated to the prescription dose or greater for the HR-CTV compared with that using MRI. MRI remains the standard for CTV definition.
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              The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix.

              This report presents guidelines for using high-dose-rate (HDR) brachytherapy in the management of patients with cervical cancer, taking into consideration the current availability of resources in most institutions. Members of the American Brachytherapy Society (ABS) with expertise in HDR brachytherapy for cervical cancer performed a literature review, supplemented their clinical experience to formulate guidelines for HDR brachytherapy of cervical cancer. The ABS strongly recommends that definitive irradiation for cervical carcinoma must include brachytherapy as a component. Each institution should follow a consistent treatment policy when performing HDR brachytherapy, including complete documentation of treatment parameters and correlation with clinical outcome, such as pelvic control, survival, and complications. The goals are to treat Point A to at least a total low-dose-rate (LDR) equivalent of 80-85 Gy for early stage disease and 85-90 Gy for advanced stage. The pelvic sidewall dose recommendations are 50-55 Gy for early lesions and 55-65 Gy for advanced ones. The relative doses given by external beam radiation therapy (EBRT) vs. brachytherapy depend upon the initial volume of disease, the ability to displace the bladder and rectum, the degree of tumor regression during pelvic irradiation, and institutional preference. As with LDR brachytherapy, every attempt should be made to keep the bladder and rectal doses below 80 Gy and 75 Gy LDR equivalent doses, respectively. Interstitial brachytherapy should be considered for patients with disease that cannot be optimally encompassed by intracavitary brachytherapy. While recognizing that many efficacious HDR fractionation schedules exist, some suggested dose and fractionation schemes for combining the EBRT with HDR brachytherapy for each stage of disease are presented. These recommendations are intended only as guidelines, and the suggested fractionation schemes have not been thoroughly tested. The responsibility for the medical decisions ultimately rests with the treating radiation oncologist. Guidelines are established for HDR brachytherapy for cervical cancer. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as image-based treatment becomes more widely available.
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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
                29 April 2019
                April 2019
                : 11
                : 2
                : 189-193
                Affiliations
                Ramaiah Medical College Bengaluru, India
                Author notes
                Address for correspondence: Revathy Thangaraj, MSc, Medical Physics, Department of Radiotherapy, Ramaiah Medical College Bengaluru, 560054 India. phone: +91 23608888, fax: +91 23601924, ext. 2243. e-mail: revamscmedphy@ 123456gmail.com
                Article
                36439
                10.5114/jcb.2019.84586
                6536140
                Copyright: © 2019 Termedia Sp. z o. o.

                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, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                Categories
                Original Paper

                Oncology & Radiotherapy

                brachytherapy, eqd2, cervical cancer

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