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      Stereotactic Ablative Brachytherapy: Recent Advances in Optimization of Radiobiological Cancer Therapy

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          Abstract

          Simple Summary

          Emerging studies involving ablative brachytherapy with curative effect have been published, but the evidence was not comprehensively discussed. This study will provide an overview of stereotactic ablative brachytherapy, focusing on the advances in stereotactic ablative brachytherapy optimization, and provide insights on the future benefits of the combined application of stereotactic ablative brachytherapy with cancer immunotherapies.

          Abstract

          Brachytherapy (BT), a type of focal anti-cancer radiotherapy, delivers a highly focused radiation dose to localized tumors, sparing surrounding normal tissues. Recent technological advances have helped to increase the accuracy of BT and, thus, improve BT-based cancer treatment. Stereotactic ablative brachytherapy (SABT) was designed to improve the ablative effect of radiation, which was achieved via improved image guidance, and calculation of ablative dose, shorter treatment duration, and better organ preservation. Recently collected data characterized SABT as having the potential to cure various early-stage cancers. The method provides higher tumor control rate levels that were previously achievable only by surgical resection. Notably, SABT is suitable for application with unresectable malignancies. However, the pathological assessment of SABT irradiated tumors is limited due to difficulties in specimen acquisition. Prostate, lung, liver, and gynecological cancers are the most commonly reported SABT-treated malignancies. This study will give an overview of SABT, focusing on the advances in SABT optimization, and provide insights on the future benefits of the combined application of SABT with cancer immunotherapies.

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          Most cited references124

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          Thermal ablation of tumours: biological mechanisms and advances in therapy.

          Minimally invasive thermal ablation of tumours has become common since the advent of modern imaging. From the ablation of small, unresectable tumours to experimental therapies, percutaneous radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation have an increasing role in the treatment of solid neoplasms. This Opinion article examines the mechanisms of tumour cell death that are induced by the most common thermoablative techniques and discusses the rapidly developing areas of research in the field, including combinatorial ablation and immunotherapy, synergy with conventional chemotherapy and radiation, and the development of a new ablation modality in irreversible electroporation.
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            Radiotherapy toxicity

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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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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                12 July 2021
                July 2021
                : 13
                : 14
                : 3493
                Affiliations
                [1 ]Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, China; xuehui@ 123456bjmu.edu.cn (H.X.); qiubin@ 123456pku.edu.cn (B.Q.); hhbysy@ 123456126.com (H.W.); bysyjiangping@ 123456163.com (P.J.)
                [2 ]Discipline of Health Sciences, College of Nursing and Health Sciences, Flinders University of South Australia, Bedford Park, SA 5042, Australia; olga.sukocheva@ 123456flinders.edu.au
                [3 ]Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; fanruitai@ 123456126.com
                Author notes
                [* ]Correspondence: lixiangxue@ 123456bjmu.edu.cn (L.X.); junjiewang@ 123456pku.edu.cn (J.W.); Tel.: +86-13701076310 (L.X.); +86-13701076310 (J.W.)
                [†]

                These authors have contributed equally to this work and should be considered co-first authors.

                Author information
                https://orcid.org/0000-0001-5634-8311
                https://orcid.org/0000-0003-1133-5562
                https://orcid.org/0000-0003-1041-3311
                https://orcid.org/0000-0002-1388-076X
                Article
                cancers-13-03493
                10.3390/cancers13143493
                8304109
                34298703
                389fc824-a1ae-42b9-b0a9-d8fa1697fa23
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 08 June 2021
                : 07 July 2021
                Categories
                Review

                brachytherapy,ablation,radiotherapy,cancer,seed implantation

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