Special Issue "New Developments in Radiotherapy"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 31 October 2018

Special Issue Editors

Guest Editor
Prof. Dr. Nicola Curtin

Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
Website | E-Mail
Interests: DNA damage response: PARP, ATR, CHK1, ATM, DNA-PK. Functional biomarkers of DNA repair
Guest Editor
Dr. Jason Parsons

Department of Molecular and Clinical Cancer Medicine, Cancer Research Centre, University of Liverpool, 200 London Road, Liverpool L3 9TA, UK
Website | E-Mail
Interests: radiation biology; proton beam therapy; DNA damage; DNA repair; base excision repair

Special Issue Information

Dear Colleagues,

More than half of all cancer patients receive radiotherapy as part of their treatment, and 40 % of all patients who are cured of cancer have received radiotherapy. Radiotherapy is also used for palliation and is one of the most cost-effective treatments for cancer. Recent years have seen several major developments in how radiotherapy is given with the use of image-guided high precision external beam radiation such as stereotactic radiotherapy (SBRT and SABR) hypofractionation, proton beam therapy as well as developments in the use of brachytherapy and targeted radionuclides. Moreover several novel combinations beyond the conventional cytotoxic radiosensitisers using molecularly-targeted agents directed at the DNA damage response, hypoxia, metabolism and angiogenesis, as well as immunotherapy agents, are under investigation. These developments have been supported by preclinical investigations that have benefitted from improvements in small animal imaging and irradiation (SARRP). The aim of this Special Issue is to provide an up-to-date overview of these new developments.

Prof. Dr. Nicola Curtin
Dr. Jason Parsons
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

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Research

Open AccessArticle Phase I Study of Carbon Ion Radiotherapy and Image-Guided Brachytherapy for Locally Advanced Cervical Cancer
Cancers 2018, 10(9), 338; https://doi.org/10.3390/cancers10090338
Received: 17 August 2018 / Revised: 12 September 2018 / Accepted: 13 September 2018 / Published: 18 September 2018
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Abstract
A phase I study was performed to determine the recommended dose of carbon ion radiotherapy and 3D image-guided brachytherapy for histologically confirmed stage II (≥4 cm), III, or IVA cervical cancer. Dose-limiting toxicities (treatment-related toxicities occurring within three months from the start of
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A phase I study was performed to determine the recommended dose of carbon ion radiotherapy and 3D image-guided brachytherapy for histologically confirmed stage II (≥4 cm), III, or IVA cervical cancer. Dose-limiting toxicities (treatment-related toxicities occurring within three months from the start of carbon ion radiotherapy) included Grade 3 non-hematological toxicity, Grade 4 hematological toxicity, or interruption of treatment for more than two weeks due to treatment-related toxicities. Carbon ion radiotherapy consisted of whole-pelvic irradiation with 36.0 Gy (relative biological effectiveness) in 12 fractions and local boost with 19.2 Gy in four fractions for the primary site, and for positive lymph nodes. Three sessions of three-dimensional (3D) image-guided brachytherapy were administered after completion of carbon ion radiotherapy. Weekly cisplatin at a dose of 40 mg/m2 was given concurrently. At a dose level of one, a total rectosigmoid D2cc dose between 67.2 Gy and 71.3 Gy at a biological equivalent dose of 2 Gy per fraction from carbon ion radiotherapy and 3D image-guided brachytherapy was prescribed. Six patients were enrolled into this dose level. No patients developed the pre-defined dose-limiting toxicities. For late toxicities, however, one patient developed Grade 3 rectal hemorrhage requiring transfusion at 10 months after treatment. The median survival time was 50.0 months for the five surviving patients. No further dose escalation was performed, and we determined the dose of level one as the recommended rectosigmoid dose. Although our results are preliminary, the study regimen encourages further investigation (registration: UMIN000013340). Full article
(This article belongs to the Special Issue New Developments in Radiotherapy)
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Open AccessArticle High-Dose-Rate Brachytherapy Monotherapy versus Image-Guided Intensity-Modulated Radiotherapy with Helical Tomotherapy for Patients with Localized Prostate Cancer
Cancers 2018, 10(9), 322; https://doi.org/10.3390/cancers10090322
Received: 6 August 2018 / Revised: 7 September 2018 / Accepted: 8 September 2018 / Published: 10 September 2018
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Abstract
The aim of this paper is to compare outcomes between high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy and image-guided intensity-modulated radiotherapy (IG-IMRT) for localized prostate cancer. We examined 353 HDR-BT and 270 IG-IMRT patients. To reduce background selection bias, we used the method of inverse
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The aim of this paper is to compare outcomes between high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy and image-guided intensity-modulated radiotherapy (IG-IMRT) for localized prostate cancer. We examined 353 HDR-BT and 270 IG-IMRT patients. To reduce background selection bias, we used the method of inverse probability treatment weighting (IPTW) with propensity scores. The actuarial five-year biochemical failure-free survival rates were 92.9% and 96.7% (p = 0.1847; p = 0.077 in IPTW) for HDR-BT and IG-IMRT, respectively; they were 100% and 95.8% (p = 0.286) for the low-risk group, 95.6% and 92% (p = 0.42) for the intermediate-risk group, 90.4% and 84.9% (p = 0.1059; p = 0.04 in IPTW) for the high-risk group, and 87.1% and 89.2% (p = 0.3816) for the very-high-risk group. In the assessment of accumulated incidences of grade ≥ 2 toxicity (Common Terminology Criteria for Adverse Events version 4.0) at five years, HDR-BT monotherapy showed higher genitourinary toxicity (11.9%) than IG-IMRT (3.3%) (p < 0.0001). The gastrointestinal toxicity was equivalent for HDR-BT (2.3%) and IG-IMRT (5.5%) (p = 0.063). No Grade 4 or 5 toxicity was detected in either modality. HDR-BT showed higher genitourinary toxicity than IG-IMRT. HDR-BT and IG-IMRT showed equivalent outcomes in low-, intermediate-, and very-high-risk groups. For high-risk patients, HDR-BT showed potential to improve prostate-specific antigen (PSA) control rate compared to IG-IMRT. Full article
(This article belongs to the Special Issue New Developments in Radiotherapy)
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Open AccessFeature PaperArticle The Impact of p53 Dysfunction in ATR Inhibitor Cytotoxicity and Chemo- and Radiosensitisation
Cancers 2018, 10(8), 275; https://doi.org/10.3390/cancers10080275
Received: 2 July 2018 / Revised: 27 July 2018 / Accepted: 14 August 2018 / Published: 20 August 2018
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Abstract
Ataxia telangiectasia mutated and Rad3 related kinase (ATR) signals replication stress and DNA damage to S and G2 arrest and promotes DNA repair. Mutations in p53, critical for G1 checkpoint control, are common in cancer and predicted to confer vulnerability to ATR inhibitors.
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Ataxia telangiectasia mutated and Rad3 related kinase (ATR) signals replication stress and DNA damage to S and G2 arrest and promotes DNA repair. Mutations in p53, critical for G1 checkpoint control, are common in cancer and predicted to confer vulnerability to ATR inhibitors. Reported data on the impact of p53 status are variable possibly because of the use of unmatched cells and surrogate endpoints of survival. The cytotoxicity of VE-821 alone and its ability to potentiate radiation and gemcitabine cytotoxicity was determined in isogenic and unmatched p53 wild-type (wt) and null/mutant cells, as well as immortalised nonmalignant MCF10 (immortalised non-neoplastic) cells, by colony-forming assay. The effect on cell cycle checkpoints was determined by flow cytometry. The isogenic p53 defective cells were not more sensitive to VE-821 alone. Defective p53 consistently conferred greater chemo- and radiosensitisation, particularly at high dose levels in isogenic cells but not unmatched cells. VE-821 did not sensitise MCF10 cells. We conclude that p53 status is just one factor contributing to chemo- and radiosensitisation by ATR inhibition, the lack of chemo- or radiosensitisation in the noncancerous cells suggests an element of tumour-specificity that warrants further investigation. The greater sensitisation at high-dose irradiation suggests that ATR inhibitors may be most effective with hypofractionated radiotherapy. Full article
(This article belongs to the Special Issue New Developments in Radiotherapy)
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