Topic Editors

Prof. Dr. Chang Ming Charlie Ma
Radiation Oncology Department, Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111, USA
Dr. Ka Yu Tse
Division of Gynaecology Oncology, Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, Hong Kong
Dr. Ming-Yii Huang
Department of Radiation Oncology, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Prof. Dr. Mukund Seshadri
Center for Oral Oncology, Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, NY 14263, USA

Cancer Biology and Radiation Therapy

Abstract submission deadline
18 May 2023
Manuscript submission deadline
20 July 2023
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Topic Information

Dear Colleagues,

Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor (for example, early stages of breast cancer). Radiation therapy is synergistic with chemotherapy and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology.

Prof. Dr. Chang Ming Charlie Ma
Dr. Ka Yu Tse
Dr. Ming-Yii Huang
Prof. Dr. Mukund Seshadri
Topic Editors

Keywords

  • cancer biology
  • radiotherapy
  • radiation oncology

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Cancers
cancers
6.575 5.8 2009 17.4 Days 2400 CHF Submit
Current Oncology
curroncol
3.109 3.5 1994 20.5 Days 1800 CHF Submit
Journal of Clinical Medicine
jcm
4.964 4.4 2012 20.6 Days 2400 CHF Submit
Medicina
medicina
2.948 2.7 1920 21.5 Days 1800 CHF Submit
Onco
onco
- - 2021 15.0 days * 1000 CHF Submit
Radiation
radiation
- - 2021 15.0 days * 1000 CHF Submit

* Median value for all MDPI journals in the second half of 2021.

Published Papers (8 papers)

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Article
Effect of Autophagy Inhibitors on Radiosensitivity in DNA Repair-Proficient and -Deficient Glioma Cells
Medicina 2022, 58(7), 889; https://doi.org/10.3390/medicina58070889 (registering DOI) - 02 Jul 2022
Abstract
Background and Objectives: The development of radioresistance is a fundamental barrier to successful glioblastoma therapy. Autophagy is thought to play a role in facilitating the DNA repair of DNA damage foci in radiation-exposed tumor cells, thus, potentially contributing to their restoration of [...] Read more.
Background and Objectives: The development of radioresistance is a fundamental barrier to successful glioblastoma therapy. Autophagy is thought to play a role in facilitating the DNA repair of DNA damage foci in radiation-exposed tumor cells, thus, potentially contributing to their restoration of proliferative capacity and development of resistance in vitro. However, the effect of autophagy inhibitors on DNA damage repair is not fully clear and requires further investigation. Materials and Methods: In this work, we utilized M059K (DNA-PKcs proficient) and M059J (DNA-PKcs deficient) glioma cell lines to investigate the role of autophagy inhibitors in the DNA repair of radiation-induced DNA damage. Cell viability following radiation was determined by trypan blue exclusion in both cell lines. Cell death and autophagy assays were performed to evaluate radiation-induced cell stress responses. DNA damage was measured as based on the intensity of phosphorylated γ-H2AX, a DNA double-stranded breaks (DSBs) marker, in the presence or absence of autophagy inhibitors. Results: The cell viability assay showed that M059J cells were more sensitive to the same dose of radiation (4 Gy) than M059K cells. This observation was accompanied by an elevation in γ-H2AX formation in M059J but not in M059K cells. In addition, the DAPI/TUNEL and Senescence-associated β-galactosidase (SA-β-gal) staining assays did not reveal significant differences in apoptosis and/or senescence induction in response to radiation, respectively, in either cell line. However, acridine orange staining demonstrated clear promotion of acidic vesicular organelles (AVOs) in both cell lines in response to 4 Gy radiation. Moreover, DNA damage marker levels were found to be elevated 72 h post-radiation when autophagy was inhibited by the lysosomotropic agent bafilomycin A1 (BafA1) or the PI3K inhibitor 3-methyl adenine (3-MA) in M059K cells. Conclusions: The extent of the DNA damage response remained high in the DNA-PKcs deficient cells following exposure to radiation, indicating their inability to repair the newly formed DNA-DSBs. On the other hand, radioresistant M059K cells showed more DNA damage response only when autophagy inhibitors were used with radiation, suggesting that the combination of autophagy inhibitors with radiation may interfere with DNA repair efficiency. Full article
(This article belongs to the Topic Cancer Biology and Radiation Therapy)
Article
Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy
Curr. Oncol. 2022, 29(6), 4274-4284; https://doi.org/10.3390/curroncol29060342 - 15 Jun 2022
Abstract
Microenvironmental conditions control the entrance and thriving of cytotoxic lymphocytes in tumors, allowing or preventing immune-mediated cancer cell death. We investigated the role of tumor-infiltrating lymphocyte (TIL) density in the outcome of radiotherapy in a series of squamous cell head–neck tumors (HNSCC). Moreover, [...] Read more.
Microenvironmental conditions control the entrance and thriving of cytotoxic lymphocytes in tumors, allowing or preventing immune-mediated cancer cell death. We investigated the role of tumor-infiltrating lymphocyte (TIL) density in the outcome of radiotherapy in a series of squamous cell head–neck tumors (HNSCC). Moreover, we assessed the link between markers of hypoxia and TIL density. One-hundred twenty-one patients with HNSCC treated prospectively with radical radiotherapy/chemo-radiotherapy were analyzed. The assessment of TIL density was performed on hematoxylin and eosin biopsy sections before radiotherapy. TIL density ranged from 0.8 to 150 lymphocytes per ×40 optical field (median 27.5). Using the median value, patients were grouped into two categories of low and high TIL density. Early T-stage tumors had a significantly higher TIL density (p < 0.003), but we found no association with N-stage. Overexpression of HIF1α, HIF2α, and CA9 was significantly linked with poor infiltration by TILs (p < 0.03). A significant association of high TIL density with better disease-specific overall survival and improved locoregional relapse-free survival was noted (p = 0.008 and 0.02, respectively), which was also confirmed in multivariate analysis. It is concluded that HNSCC phenotypes that allow for the intratumoral accumulation of lymphocytes have a better outcome following radical radiotherapy/chemo-radiotherapy. Intratumoral-activated HIF- and CA9-related pathways characterize immunologically cold tumors and may be used as targets for therapeutic interventions. Full article
(This article belongs to the Topic Cancer Biology and Radiation Therapy)
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Article
Extra-Pleural Pneumonectomy (EPP) in Children and Adults with Locally Advanced Sarcoma: A CanSaRCC Study
Curr. Oncol. 2022, 29(6), 4260-4266; https://doi.org/10.3390/curroncol29060340 - 15 Jun 2022
Abstract
Sarcoma can present as locally advanced disease involving pleura for which extra-pleural pneumonectomy (EPP) may be the only surgical option to ensure adequate local control. Data were collected on patients who underwent EPP between January 2009 and August 2021 at Princess Margret Hospital [...] Read more.
Sarcoma can present as locally advanced disease involving pleura for which extra-pleural pneumonectomy (EPP) may be the only surgical option to ensure adequate local control. Data were collected on patients who underwent EPP between January 2009 and August 2021 at Princess Margret Hospital and SickKids (Toronto) using the CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration). Ten patients with locally advanced sarcoma involving the pleura, aged 4 to 59 years (median 19.5 years) underwent EPP. Nine (90%) received pre-operative chemotherapy and eight (80%) achieved an R0 resection. Hemithoracic radiation was administered preoperatively (n = 6, 60%) or postoperatively (n = 4, 40%). Five (50%) patients were alive without disease at last follow-up (median 34.2 months) and time from EPP to last FU was median 29.2 months (range 2.2–87.5). Two patients (20%) had local recurrence, 4.3 and 5.8 months from EPP, and both died from progressive disease, 13.1 and 8.2 months from EPP, respectively. One patient died from brain metastasis (17 months), one died from radiation associated osteosarcoma (66 months), and one died from surgical complications (heart failure from constrictive pericarditis). EPP offers a feasible and life-prolonging surgical consideration for patients with locally advanced sarcoma involving the pleura in combination with chemotherapy and radiation. Consequently, EPP should be considered during multi-disciplinary tumor board discussions at high-volume centers. Full article
(This article belongs to the Topic Cancer Biology and Radiation Therapy)
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Article
Ultra-Hypofractionated vs. Moderate Fractionated Whole Breast Three Dimensional Conformal Radiotherapy during the COVID-19 Pandemic
Medicina 2022, 58(6), 745; https://doi.org/10.3390/medicina58060745 - 30 May 2022
Abstract
Background and Objectives: Reducing time of treatment during COVID-19 outbreaks has been recommended by the leading Radiation Oncology societies. Still minimizing radiation induced tissue toxicity is one of the most important issues in breast cancer patients. The study aimed to investigate compliance, [...] Read more.
Background and Objectives: Reducing time of treatment during COVID-19 outbreaks has been recommended by the leading Radiation Oncology societies. Still minimizing radiation induced tissue toxicity is one of the most important issues in breast cancer patients. The study aimed to investigate compliance, clinical and dosimetry normal tissue toxicity, and cosmetic results between moderated and ultra-fractionated regimes for breast cancer patients during COVID-19 pandemic. Materials and Methods: This pilot prospective randomized study included 60 patients with early breast cancer after preserving surgery, 27 patients advocated to ultra-hypofractionated whole-breast three dimensional (3D) conformal radiotherapy of 26 Gy in 5 fractions over 1 week and 33 patients with moderate fractionated breast 3D conformal radiotherapy patients between March 2020 and July 2020, during the COVID pandemic outbreak. The compliance to treatment, dosimetric parameters, acute and late skin toxicity, subcutaneous tissue toxicity, cosmetic results and clinical follow up for 18 months for the two regimes were analyzed and compared. Results: When two regimes were compared 5 fraction group had significantly lower prevalence of newly infected cases of SARS-CoV-2 and thus delayed/interrupted treatment (p = 0.05), comparable grade 1 CTCAE v5, acute skin toxicity (p = 0.18), Grade 1 Radiation Morbidity Scoring Scheme (RESS) subcutaneous tissue toxicity (p = 0.18), Grade 1 RESS late skin toxicity (p = 0.88) and cosmetic results (p = 0.46). Dosimetric results reveled that patients in 5 fraction group received significantly lower median ipsilateral lung doses (p < 0.01) in addition to left breast cancer patients that received significantly lower median heart dose (p < 0.01) and median left anterior descending artery (LAD) dose (p < 0.01). Conclusion: Ultra-hypofractionated radiotherapy for breast cancer is comparable to moderate hypofractionation regimen regarding grade 1 acute skin toxicity, grade 1 subcutaneous tissue toxicity, late skin toxicity and cosmetic results. Application of ultra-hypofractionated radiotherapy with significantly lower radiation doses for lung and heart could be crucial in reducing the risk of acute/late pulmonary and heart radiation-induced toxicity. Full article
(This article belongs to the Topic Cancer Biology and Radiation Therapy)
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Article
Specific MRP4 Inhibitor Ceefourin-1 Enhances Apoptosis Induced by 6-Mercaptopurine in Jurkat Leukemic Cells, but Not in Normal Lymphoblast Cell Line CRL-1991
Medicina 2022, 58(6), 695; https://doi.org/10.3390/medicina58060695 - 24 May 2022
Abstract
Background and objectives: The multidrug resistance protein 4 (MRP4) is a member of the ABC transporter, which has been extensively related to many types of cancer including leukemia. MRP4 overexpression and activity over the efflux of some chemotherapeutic drugs are the main [...] Read more.
Background and objectives: The multidrug resistance protein 4 (MRP4) is a member of the ABC transporter, which has been extensively related to many types of cancer including leukemia. MRP4 overexpression and activity over the efflux of some chemotherapeutic drugs are the main causes of chemoresistance. 6-mercaptopurine (6-MP) is a chemotherapeutic drug widely used in the consolidation and maintenance phases of leukemia treatment. However, 6-MP is a substrate of MRP4, which decreases its chemotherapeutic efficacy. Current research is focused on the development of MRP4 inhibitors to combat chemoresistance by allowing the accumulation of the drug substrates inside the cells. To date, the only specific MRP4 inhibitor that has been developed is ceefourin-1, which has been reported to inhibit MRP4 in many cancer cells and which makes it an excellent candidate to enhance the activity of 6-MP in a combined treatment in vitro of leukemic cells. Materials and methods: in the present work, we determined the enhancing activity of ceefourin-1 on the antiproliferative and apoptotic effect of 6-MP in leukemic Jurkat cells by trypan blue assay and flow cytometry. Besides, we determined the 6-MP and ceefourin-1 binding sites into MRP4 by molecular docking and molecular dynamics. Results: ceefourin-1 enhanced the apoptotic activity of 6-MP in Jurkat cells, while in CRL-1991 cells both antiproliferative and apoptotic effect were significantly lower. Ceefourin-1 additively cooperates with 6-MP to induce apoptosis in leukemic cells, but normal lymphoblast CRl-1991 showed resistance to both drugs. Conclusion: ceefourin-1 and 6-MP cooperates to trigger apoptosis in leukemic Jurkat cells, but the full mechanism needs to be elucidated in further works. In addition, our perspective is to test the cooperation between ceefourin-1 and 6-MP in samples from patients and healthy donnors. Full article
(This article belongs to the Topic Cancer Biology and Radiation Therapy)
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Article
Clinical Imaging and Dosimetry of a Pan-Cancer Targeting Alkylphosphocholine Analog, [124I]I-NM404
Radiation 2022, 2(2), 215-227; https://doi.org/10.3390/radiation2020015 - 17 May 2022
Abstract
The purpose of this study was to assess organ dosimetry and clinical use of [124I]I-NM404, a radiotheranostic alkylphosphocholine (APC) analog, for accurate detection and characterization of a wide variety of solid primary and metastatic malignancies anywhere in the body. Methods: Patterns [...] Read more.
The purpose of this study was to assess organ dosimetry and clinical use of [124I]I-NM404, a radiotheranostic alkylphosphocholine (APC) analog, for accurate detection and characterization of a wide variety of solid primary and metastatic malignancies anywhere in the body. Methods: Patterns of [124I]I-NM404 uptake were quantitatively analyzed and qualitatively compared with [18F]FDG PET/CT in 14 patients (median age, 61.5 years; 7 males, 7 females) with refractory metastatic cancer who were enrolled in one of two Phase I imaging studies. Primary cancer types included bronchogenic (n = 7), colorectal (n = 1), prostate (n = 1), triple-negative breast (n = 1), head and neck (n = 2), pancreatic (n = 1) carcinoma, and melanoma (n = 1). Patients were administered [124I]I-NM404 and imaged via PET/CT at 1–2, 4–6, 24, and 48 h and at 5–10 days post injection, from top of the skull to mid-thigh. Volumes of interest were drawn over lungs, heart, liver, kidneys, and whole body for dosimetry estimation using OLINDA 1.1 Representative metastatic index lesions were chosen when applicable for each case with active sites of disease to calculate maximum and mean tumor-to-background ratios (TBRmax, TBRmean), using the adjacent normal organ parenchyma as background when possible. Results: Administrations of [124I]-NM404 were safe and well-tolerated. The organs with the highest estimated absorbed dose (mean ± SD) were the lungs (1.74 ± 0.39 mSv/MBq), heart wall (1.52 ± 0.29 mSv/MBq), liver (1.28 ± 0.21 mSv/MBq) and kidneys (1.09 ± 0.20 mSv/MBq). The effective dose was 0.77 ± 0.05 mSv/MBq. Preferential uptake within metastatic foci was observed with all cancer subtypes, TBRmax ranged from 1.95 to 15.36 and TBRmean ranged from 1.63 to 6.63. Robust sensitive imaging of lesions was enhanced by delayed timing (2–6 days after single injection of [124I]I-NM404, respectively) due to persistent tumor retention coupled with progressive washout of background activity. NM404 uptake was evident in pulmonary, nodal, skeletal, CNS, and other metastatic sites of disease. Radiation related injury or necrosis were NM404 negative, whereas certain small number of metastatic brain lesions were false negative for NM404. Conclusions: In addition to being well tolerated, selective tumor uptake of NM404 with prolonged retention was demonstrated within a broad spectrum of highly treated metastatic cancers. Full article
(This article belongs to the Topic Cancer Biology and Radiation Therapy)
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Systematic Review
Optimal Clinical Target Volume of Radiotherapy Based on Microscopic Extension around the Primary Gross Tumor in Non-Small-Cell Lung Cancer: A Systematic Review
Cancers 2022, 14(9), 2318; https://doi.org/10.3390/cancers14092318 - 07 May 2022
Abstract
A crucial issue in radical radiation therapy for non-small-cell lung cancer is how to define the clinical target volume (CTV). Although the scope of microscopic extension (ME) and microscopic proximal bronchial extension (PBE) from a primary tumor should be considered when defining the [...] Read more.
A crucial issue in radical radiation therapy for non-small-cell lung cancer is how to define the clinical target volume (CTV). Although the scope of microscopic extension (ME) and microscopic proximal bronchial extension (PBE) from a primary tumor should be considered when defining the CTV, there has been limited research on ME and PBE. Therefore, we conducted this systematic review. The PubMed, ICHUSHI (Japanese database), and Cochrane Library databases were searched, and 816 articles were initially retrieved. After primary and secondary screenings, eight articles were ultimately selected. The results of this systematic review suggest the importance of a 0 mm margin in stereotactic radiotherapy for early-stage cancer and a 5–8 mm margin in curative irradiation for locally advanced cancer. Regarding PBE, this review yielded the conclusion that it is appropriate to consider the addition of an approximately 15 mm margin from the bronchial vasculature. Although there were few articles with a high level of evidence, this systematic review enabled us to collate results from previous studies and to provide recommendations, to some extent, regarding the CTV margin in the current clinical environment, where high-precision radiation therapy, such as image-guided radiotherapy and intensity-modulated radiotherapy, is predominant. Full article
(This article belongs to the Topic Cancer Biology and Radiation Therapy)
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Article
A Comparative Analysis of Photon versus Proton Beam Therapy in Neoadjuvant Concurrent Chemoradiotherapy for Intrathoracic Squamous Cell Carcinoma of the Esophagus at a Single Institute
Cancers 2022, 14(8), 2033; https://doi.org/10.3390/cancers14082033 - 18 Apr 2022
Abstract
Background: Proton beam therapy (PBT), as a neoadjuvant chemoradiotherapy (nCRT) modality, is expected to result in better outcomes than photon-based radiotherapy (RT) for esophageal cancer, particularly adenocarcinoma. This study reports the results of nCRT for locally advanced esophageal squamous cell carcinoma (ESCC) using [...] Read more.
Background: Proton beam therapy (PBT), as a neoadjuvant chemoradiotherapy (nCRT) modality, is expected to result in better outcomes than photon-based radiotherapy (RT) for esophageal cancer, particularly adenocarcinoma. This study reports the results of nCRT for locally advanced esophageal squamous cell carcinoma (ESCC) using both modalities. Methods: We retrospectively reviewed the records of patients who underwent nCRT for ESCC between 2001 and 2020. A median of 41.4 Gy or cobalt gray equivalents of radiation was delivered using either photons or protons, with concurrent chemotherapy. Dosimetric and clinical parameters were compared between the two groups. Results: Of the 31 patients, the lungs and heart of the proton group (n = 15) were exposed to significantly less radiation compared to the photon group (n = 16). No significant differences in short-term postoperative outcomes or lymphocyte count were observed between the groups, and there were no significant differences between the photon and proton groups in 2-year overall survival (67.8% vs. 68.6%, p = 0.867) or 2-year disease-free survival (33.3% vs. 34.5%, p = 0.749), with a median follow-up of 17 months. Conclusions: PBT provided a significant dosimetric benefit over photon-based RT during nCRT for ESCC; however, it did not improve clinical outcomes. Full article
(This article belongs to the Topic Cancer Biology and Radiation Therapy)
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