Special Issue "New Developments in Radiotherapy"

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

Deadline for manuscript submissions: closed (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 (6 papers)

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Research

Open AccessArticle Automated Knowledge-Based Intensity-Modulated Proton Planning: An International Multicenter Benchmarking Study
Cancers 2018, 10(11), 420; https://doi.org/10.3390/cancers10110420
Received: 28 August 2018 / Revised: 12 October 2018 / Accepted: 29 October 2018 / Published: 2 November 2018
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Abstract
Background: Radiotherapy treatment planning is increasingly automated and knowledge-based planning has been shown to match and sometimes improve upon manual clinical plans, with increased consistency and efficiency. In this study, we benchmarked a novel prototype knowledge-based intensity-modulated proton therapy (IMPT) planning solution, against
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Background: Radiotherapy treatment planning is increasingly automated and knowledge-based planning has been shown to match and sometimes improve upon manual clinical plans, with increased consistency and efficiency. In this study, we benchmarked a novel prototype knowledge-based intensity-modulated proton therapy (IMPT) planning solution, against three international proton centers. Methods: A model library was constructed, comprising 50 head and neck cancer (HNC) manual IMPT plans from a single center. Three external-centers each provided seven manual benchmark IMPT plans. A knowledge-based plan (KBP) using a standard beam arrangement for each patient was compared with the benchmark plan on the basis of planning target volume (PTV) coverage and homogeneity and mean organ-at-risk (OAR) dose. Results: PTV coverage and homogeneity of KBPs and benchmark plans were comparable. KBP mean OAR dose was lower in 32/54, 45/48 and 38/53 OARs from center-A, -B and -C, with 23/32, 38/45 and 23/38 being >2 Gy improvements, respectively. In isolated cases the standard beam arrangement or an OAR not being included in the model or being contoured differently, led to higher individual KBP OAR doses. Generating a KBP typically required <10 min. Conclusions: A knowledge-based IMPT planning solution using a single-center model could efficiently generate plans of comparable quality to manual HNC IMPT plans from centers with differing planning aims. Occasional higher KBP OAR doses highlight the need for beam angle optimization and manual review of KBPs. The solution furthermore demonstrated the potential for robust optimization. Full article
(This article belongs to the Special Issue New Developments in Radiotherapy)
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Open AccessArticle Dosimetric Comparison of Proton Radiation Therapy, Volumetric Modulated Arc Therapy, and Three-Dimensional Conformal Radiotherapy Based on Intracranial Tumor Location
Cancers 2018, 10(11), 401; https://doi.org/10.3390/cancers10110401
Received: 1 October 2018 / Revised: 18 October 2018 / Accepted: 23 October 2018 / Published: 26 October 2018
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Abstract
(1) Background: Selecting patients that will benefit the most from proton radiotherapy (PRT) is of major importance. This study sought to assess dose reductions to numerous organs-at-risk (OARs) with PRT, as compared to three-dimensional conformal radiotherapy (3DCRT) and volumetric-modulated arc therapy (VMAT), as
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(1) Background: Selecting patients that will benefit the most from proton radiotherapy (PRT) is of major importance. This study sought to assess dose reductions to numerous organs-at-risk (OARs) with PRT, as compared to three-dimensional conformal radiotherapy (3DCRT) and volumetric-modulated arc therapy (VMAT), as a function of tumor location. (2) Materials/Methods: Patients with intracranial neoplasms (all treated with PRT) were stratified into five location-based groups (frontal, suprasellar, temporal, parietal, posterior cranial fossa; n = 10 per group). Each patient was re-planned for 3DCRT and intensity-modulated radiotherapy (IMRT) using similar methodology, including the originally planned target and organ-at-risk (OAR) dose constraints. (3) Results: In parietal tumors, PRT showed the most pronounced dose reductions. PRT lowered doses to nearly every OAR, most notably the optical system and several contralateral structures (subventricular zone, thalamus, hippocampus). For frontal lobe cases, the greatest relative dose reductions in mean dose (Dmean) with PRT were to the infratentorial normal brain, contralateral hippocampus, brainstem, pituitary gland and contralateral optic nerve. For suprasellar lesions, PRT afforded the greatest relative Dmean reductions to the infratentorial brain, supratentorial brain, and the whole brain. Similar results could be observed in temporal and posterior cranial fossa disease. (4) Conclusions: The effectiveness and degree of PRT dose-sparing to various OARs depends on intracranial tumor location. These data will help to refine selection of patients receiving PRT, cost-effectiveness, and future clinical toxicity assessment. Full article
(This article belongs to the Special Issue New Developments in Radiotherapy)
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Open AccessFeature PaperArticle Accelerated Hypofractionated Active Raster-Scanned Carbon Ion Radiotherapy (CIRT) for Laryngeal Malignancies: Feasibility and Safety
Cancers 2018, 10(10), 388; https://doi.org/10.3390/cancers10100388
Received: 17 September 2018 / Revised: 15 October 2018 / Accepted: 16 October 2018 / Published: 18 October 2018
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Abstract
(1) Background: The authors present the first results of active raster-scanned carbon ion radiotherapy (CIRT) for radioresistant laryngeal malignancies regarding efficacy and toxicity. (2) Methods: 15 patients with laryngeal adenoid cystic carcinoma (ACC; n = 8; 53.3%) or chondrosarcoma (CS; n = 7;
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(1) Background: The authors present the first results of active raster-scanned carbon ion radiotherapy (CIRT) for radioresistant laryngeal malignancies regarding efficacy and toxicity. (2) Methods: 15 patients with laryngeal adenoid cystic carcinoma (ACC; n = 8; 53.3%) or chondrosarcoma (CS; n = 7; 46.7%) who underwent radiotherapy with carbon ions (C12) at the Heidelberg Ion Beam Therapy Center (HIT) between 2013 and 2018 were identified retrospectively and analyzed for local control (LC), overall survival (OS), and distant progression-free survival using the Kaplan–Meier method. CIRT was applied either alone (n = 7, 46.7%) or in combination with intensity modulated radiotherapy (IMRT) (n = 8, 53.3%). The toxicity was assessed according to the Common Toxicity Terminology Criteria for Adverse Events (CTCAE) v4.03. (3). Results: the median follow-up was 24 months (range 5–61 months). Overall, the therapy was tolerated very well. No grade >3 acute and chronic toxicity could be identified. The most reported acute grade 3 side effects were acute dysphagia (n = 2; 13%) and acute odynophagia (n = 3; 20%), making supportive nutrition via gastric tube (n = 2; 13.3%) and via high caloric drinks (n = 1; 6.7%) necessary due to swallowing problems (n = 4; 27%). Overall, chronic grade 3 toxicity in the form of chronic hoarseness occurred in 7% of the patients (n = 1; 7%). At the last follow-up, all the patients were alive. No local or locoregional recurrence could be identified. Only one patient with laryngeal ACC developed lung metastases three years after the first diagnosis. (4) Conclusions: the accelerated hypofractionated active raster-scanned carbon ion radiotherapy for radioresistant laryngeal malignancies is feasible in practice with excellent local control rates and moderate acute and late toxicity. Further follow-ups are necessary to evaluate the long-term clinical outcome. Full article
(This article belongs to the Special Issue New Developments in Radiotherapy)
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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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