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The Future of Radiation Research in Cancers

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Methods and Technologies Development".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 12191

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Dr. Lisa Deloch

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Radiation Osteoimmunology, Translational Biology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
Interests: osteoimmunology; radiation research; low-dose radiotherapy; arthritis; radiation biology; radiation protection; X-rays
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Dr. Johann Matschke

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Institute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
Interests: metabolism; radiation response; tumor microenvironment; hypoxia; DNA repair
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Dr. Michael Rückert

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Radiation Immunobiology Group, Translational Biology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
Interests: immunology; immune checkpoint molecules; cancer vaccines; radiotherapy, immune cells; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The future of radiation research is a highly translational research area that integrates specific expertise in various areas of cancer and radiation biology, physics, experimental and clinical (radio)-oncology, and computational biology. The mission is to create strong added value and potential for innovation in the internationally emerging field of molecular personalization in radiation oncology by creating synergies through teamwork.

In order to move forward within this highly translational research field and the future of radiation science, it is important to foster the development of advanced model systems, technical methods, and novel approaches as well as the improvement of existing therapy strategies. All of these improvements will need to focus on both tumor and normal tissue responses with the aim to gain a better understanding of the underlying molecular effects, helping to ultimately improve the outcome and survival in patients.

This Special Issue aims to highlight (translational) innovative approaches with a special focus on young scientists contributing to the development in the field of radiation research including original basic and translational research, technical developments, and novel model systems, as well as clinical studies on various tumor types and from different scientific backgrounds and review articles covering the following major topics:

FundamentalMechanisms in (Bio)Physics and DNA Repair
Radiobiology of Non-Ionisingand High-LET Radiation
Novel Strategies for Modulating Tumor Response and Anti-Tumor Immune Reactions
Translational Research—from Bench to Bedside
Radiation Response and Radiation Protection in Non-Malignant Cells and Normal Tissues

Keywords

radiation research
cancer
biophysics
ionizing radiation
immune system
radiotherapy
(radio)immunotherapy
(radio)chemotherapy
normal tissue response

Related Special Issue

The Future of Radiation Research in Cancers, 2nd Edition in Cancers

Published Papers (8 papers)

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Research

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13 pages, 2366 KiB

Open AccessArticle

Dosimetric Comparison of Conventional Radiotherapy, Volumetric Modulated Arc Therapy, and Proton Beam Therapy for Palliation of Thoracic Spine Metastases Secondary to Breast or Prostate Cancer

by Anders Lideståhl, Emil Fredén, Albert Siegbahn, Gracinda Johansson and Pehr A. Lind

Cancers 2023, 15(24), 5736; https://doi.org/10.3390/cancers15245736 - 07 Dec 2023

Viewed by 861

Abstract

The aim of this planning study was to compare the dosimetric outcomes of Volumetric Modulated Arc Therapy (VMAT), Proton Beam Therapy (PBT), and conventional External Beam Radiation Therapy (cEBRT) in the treatment of thoracic spinal metastases originating from breast or prostate cancer. Our study utilized data from 30 different treatment plans and evaluated target coverage and doses to vital organs at risk (OARs), such as the spinal cord, heart, esophagus, and lungs. The results showed that VMAT and PBT achieved superior target coverage and significantly lower doses to the spinal cord compared to cEBRT (target: median PTV_D95%: 75.2 for cEBRT vs. 92.9 and 91.7 for VMAT (p < 0.001) and PBT (p < 0.001), respectively; spinal cord: median D_max%: 105.1 for cEBRT vs. 100.4 and 103.6 for VMAT (p < 0.001) and PBT (p = 0.002), respectively). Specifically, VMAT was notable for its superior target coverage and PBT for significantly lower doses to heart, lungs, and esophagus. However, VMAT resulted in higher lung doses, indicating potential trade-offs among different techniques. The study demonstrated the relative advantages of VMAT and PBT over traditional RT in the palliative treatment of spinal metastases using conventional fractionation. These findings underscore the potential of VMAT and PBT to improve dosimetric outcomes, suggesting that they may be more suitable for certain patient groups for whom the sparing of specific OARs is especially important. Full article

(This article belongs to the Special Issue The Future of Radiation Research in Cancers)

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22 pages, 6701 KiB

Open AccessArticle

Radiation-Induced Cellular Senescence Reduces Susceptibility of Glioblastoma Cells to Oncolytic Vaccinia Virus

by Quinn T. Storozynsky, Xuefei Han, Shae Komant, Kate C. Agopsowicz, Kyle G. Potts, Armin M. Gamper, Roseline Godbout, David H. Evans and Mary M. Hitt

Cancers 2023, 15(13), 3341; https://doi.org/10.3390/cancers15133341 - 25 Jun 2023

Cited by 1 | Viewed by 1689

Abstract

Glioblastoma (GBM) is a malignant brain cancer refractory to the current standard of care, prompting an extensive search for novel strategies to improve outcomes. One approach under investigation is oncolytic virus (OV) therapy in combination with radiotherapy. In addition to the direct cytocidal effects of radiotherapy, radiation induces cellular senescence in GBM cells. Senescent cells cease proliferation but remain viable and are implicated in promoting tumor progression. The interaction of viruses with senescent cells is nuanced; some viruses exploit the senescent state to their benefit, while others are hampered, indicating senescence-associated antiviral activity. It is unknown how radiation-induced cellular senescence may impact the oncolytic properties of OVs based on the vaccinia virus (VACV) that are used in combination with radiotherapy. To better understand this, we induced cellular senescence by treating GBM cells with radiation, and then evaluated the growth kinetics, infectivity, and cytotoxicity of an oncolytic VACV, ∆F4LΔJ2R, as well as wild-type VACV in irradiated senescence-enriched and non-irradiated human GBM cell lines. Our results show that both viruses display attenuated oncolytic activities in irradiated senescence-enriched GBM cell populations compared to non-irradiated controls. These findings indicate that radiation-induced cellular senescence is associated with antiviral activity and highlight important considerations for the combination of VACV-based oncolytic therapies with senescence-inducing agents such as radiotherapy. Full article

(This article belongs to the Special Issue The Future of Radiation Research in Cancers)

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17 pages, 2098 KiB

Open AccessArticle

The Association of Gross Tumor Volume and Its Radiomics Features with Brain Metastases Development in Patients with Radically Treated Stage III Non-Small Cell Lung Cancer

by Haiyan Zeng, Fariba Tohidinezhad, Dirk K. M. De Ruysscher, Yves C. P. Willems, Juliette H. R. J. Degens, Vivian E. M. van Kampen-van den Boogaart, Cordula Pitz, Francesco Cortiula, Lloyd Brandts, Lizza E. L. Hendriks and Alberto Traverso

Cancers 2023, 15(11), 3010; https://doi.org/10.3390/cancers15113010 - 31 May 2023

Cited by 1 | Viewed by 1200

Abstract

Purpose: To identify clinical risk factors, including gross tumor volume (GTV) and radiomics features, for developing brain metastases (BM) in patients with radically treated stage III non-small cell lung cancer (NSCLC). Methods: Clinical data and planning CT scans for thoracic radiotherapy were retrieved from patients with radically treated stage III NSCLC. Radiomics features were extracted from the GTV, primary lung tumor (GTVp), and involved lymph nodes (GTVn), separately. Competing risk analysis was used to develop models (clinical, radiomics, and combined model). LASSO regression was performed to select radiomics features and train models. Area under the receiver operating characteristic curves (AUC-ROC) and calibration were performed to assess the models’ performance. Results: Three-hundred-ten patients were eligible and 52 (16.8%) developed BM. Three clinical variables (age, NSCLC subtype, and GTVn) and five radiomics features from each radiomics model were significantly associated with BM. Radiomic features measuring tumor heterogeneity were the most relevant. The AUCs and calibration curves of the models showed that the GTVn radiomics model had the best performance (AUC: 0.74; 95% CI: 0.71–0.86; sensitivity: 84%; specificity: 61%; positive predictive value [PPV]: 29%; negative predictive value [NPV]: 95%; accuracy: 65%). Conclusion: Age, NSCLC subtype, and GTVn were significant risk factors for BM. GTVn radiomics features provided higher predictive value than GTVp and GTV for BM development. GTVp and GTVn should be separated in clinical and research practice. Full article

(This article belongs to the Special Issue The Future of Radiation Research in Cancers)

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12 pages, 824 KiB

Open AccessArticle

The Effectiveness of the Combination of Arterial Infusion Chemotherapy and Radiotherapy for Biliary Tract Cancer: A Prospective Pilot Study

by Takuma Goto, Hiroki Sato, Shugo Fujibayashi, Tetsuhiro Okada, Akihiro Hayashi, Hidemasa Kawabata, Sayaka Yuzawa, Syunta Ishitoya, Masaaki Yamashina and Mikihiro Fujiya

Cancers 2023, 15(9), 2616; https://doi.org/10.3390/cancers15092616 - 05 May 2023

Viewed by 1482

Abstract

The standard treatment of unresectable biliary tract cancer (BTC) has shown an insufficient response rate (RR). Our retrospective setting revealed that a combination therapy consisting of intra-arterial chemotherapy plus radiation therapy (IAC + RT) provided a high RR and long-term survival benefits in unresectable BTC. This prospective study aimed to test the effectiveness and safety of IAC + RT as the first-line therapy. The regimen included one-shot IAC with cisplatin, 3–6 months of reservoir IAC (5-FU and cisplatin, q/week), and 50.4 Gy of external radiation. The primary endpoints include the RR, disease control rate, and adverse event rate. This study included seven patients with unresectable BTC without distant metastasis, with five cases classified as stage 4. RT was completed in all cases, and the median number of reservoir IAC sessions was 16. The RR was 57.1% for imaging and 71.4% for clinical assessment, and the disease control rate was 100%, indicating a high antitumor efficacy, which allowed two cases to be transferred to surgery. Five cases of leukopenia and neutropenia; four cases of thrombocytopenia; and two cases of hemoglobin depletion, pancreatic enzyme elevation, and cholangitis were observed, but with no treatment-related deaths. This study revealed a very high antitumor effect with IAC + RT for some unresectable BTC, and it could be useful for conversion therapy. Full article

(This article belongs to the Special Issue The Future of Radiation Research in Cancers)

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Review

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14 pages, 2615 KiB

Open AccessReview

Nodal Elective Volume Selection and Definition during Radiation Therapy for Early Stage (T1–T2 N0 M0) Perianal Squamous Cell Carcinoma: A Narrative Clinical Review and Critical Appraisal

by Lavinia Spinelli, Stefania Martini, Salvatore Dario Solla, Riccardo Vigna Taglianti, Francesco Olivero, Luca Gianello, Alessia Reali, Anna Maria Merlotti and Pierfrancesco Franco

Cancers 2023, 15(24), 5833; https://doi.org/10.3390/cancers15245833 - 14 Dec 2023

Viewed by 895

Abstract

Distinction between anal canal and perianal squamous cell carcinomas (pSCCs) is essential, as these two subgroups have different anatomical, histological, and lymphatic drainage features. Early-stage true perianal tumors are very uncommon and have been rarely included in clinical trials. Perianal skin cancers and aCCs are included in the same tumor classification, even though they have different lymphatic drainage features. Furthermore, pSCCs are treated similarly to carcinomas originating from the anal canal. Radiation therapy (RT) is an essential treatment for anal canal tumors. Guidelines do not differentiate between treatment volumes for perianal tumors and anal cancers. So far, in pSCC, no study has considered modulating treatment volume selection according to the stage of the disease. We conducted a narrative literature review to describe the sites at higher risk for microscopic disease in patients with early-stage perianal cancers (T1–T2 N0 M0) to propose a well-thought selection of RT elective volumes. Full article

(This article belongs to the Special Issue The Future of Radiation Research in Cancers)

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22 pages, 1781 KiB

Open AccessReview

Moving the Needle Forward in Genomically-Guided Precision Radiation Treatment

by Andrew Tam, Benjamin D. Mercier, Reeny M. Thomas, Eemon Tizpa, Irene G. Wong, Juncong Shi, Rishabh Garg, Heather Hampel, Stacy W. Gray, Terence Williams, Jose G. Bazan and Yun R. Li

Cancers 2023, 15(22), 5314; https://doi.org/10.3390/cancers15225314 - 07 Nov 2023

Viewed by 1217

Abstract

Radiation treatment (RT) is a mainstay treatment for many types of cancer. Recommendations for RT and the radiation plan are individualized to each patient, taking into consideration the patient’s tumor pathology, staging, anatomy, and other clinical characteristics. Information on germline mutations and somatic tumor mutations is at present rarely used to guide specific clinical decisions in RT. Many genes, such as ATM, and BRCA1/2, have been identified in the laboratory to confer radiation sensitivity. However, our understanding of the clinical significance of mutations in these genes remains limited and, as individual mutations in such genes can be rare, their impact on tumor response and toxicity remains unclear. Current guidelines, including those from the National Comprehensive Cancer Network (NCCN), provide limited guidance on how genetic results should be integrated into RT recommendations. With an increasing understanding of the molecular underpinning of radiation response, genomically-guided RT can inform decisions surrounding RT dose, volume, concurrent therapies, and even omission to further improve oncologic outcomes and reduce risks of toxicities. Here, we review existing evidence from laboratory, pre-clinical, and clinical studies with regard to how genetic alterations may affect radiosensitivity. We also summarize recent data from clinical trials and explore potential future directions to utilize genetic data to support clinical decision-making in developing a pathway toward personalized RT. Full article

(This article belongs to the Special Issue The Future of Radiation Research in Cancers)

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25 pages, 1994 KiB

Open AccessReview

Exploring Natural Products as Radioprotective Agents for Cancer Therapy: Mechanisms, Challenges, and Opportunities

by Yi Zhang, Ying Huang, Zheng Li, Hanyou Wu, Bingwen Zou and Yong Xu

Cancers 2023, 15(14), 3585; https://doi.org/10.3390/cancers15143585 - 12 Jul 2023

Cited by 3 | Viewed by 2555

Abstract

Radiotherapy is an important cancer treatment. However, in addition to killing tumor cells, radiotherapy causes damage to the surrounding cells and is toxic to normal tissues. Therefore, an effective radioprotective agent that prevents the deleterious effects of ionizing radiation is required. Numerous synthetic substances have been shown to have clear radioprotective effects. However, most of these have not been translated for use in clinical applications due to their high toxicity and side effects. Many medicinal plants have been shown to exhibit various biological activities, including antioxidant, anti-inflammatory, and anticancer activities. In recent years, new agents obtained from natural products have been investigated by radioprotection researchers, due to their abundance of sources, high efficiency, and low toxicity. In this review, we summarize the mechanisms underlying the radioprotective effects of natural products, including ROS scavenging, promotion of DNA damage repair, anti-inflammatory effects, and the inhibition of cell death signaling pathways. In addition, we systematically review natural products with radioprotective properties, including polyphenols, polysaccharides, alkaloids, and saponins. Specifically, we discuss the polyphenols apigenin, genistein, epigallocatechin gallate, quercetin, resveratrol, and curcumin; the polysaccharides astragalus, schisandra, and Hohenbuehelia serotina; the saponins ginsenosides and acanthopanax senticosus; and the alkaloids matrine, ligustrazine, and β-carboline. However, further optimization through structural modification, improved extraction and purification methods, and clinical trials are needed before clinical translation. With a deeper understanding of the radioprotective mechanisms involved and the development of high-throughput screening methods, natural products could become promising novel radioprotective agents. Full article

(This article belongs to the Special Issue The Future of Radiation Research in Cancers)

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13 pages, 283 KiB

Open AccessReview

Companion Animals as a Key to Success for Translating Radiation Therapy Research into the Clinic

by Isabelle F. Vanhaezebrouck and Matthew L. Scarpelli

Cancers 2023, 15(13), 3377; https://doi.org/10.3390/cancers15133377 - 27 Jun 2023

Cited by 2 | Viewed by 1078

Abstract

Many successful preclinical findings fail to be replicated during translation to human studies. This leads to significant resources being spent on large clinical trials, and in some cases, promising therapeutics not being pursued due to the high costs of clinical translation. These translational failures emphasize the need for improved preclinical models of human cancer so that there is a higher probability of successful clinical translation. Companion-animal cancers offer a potential solution. These cancers are more similar to human cancer than other preclinical models, with a natural evolution over time, genetic alterations, intact immune system, and a permanent adaptation to the microenvironment. These advantages have led pioneers in veterinary radiation oncology to aid human medicine by elucidating basic principles of radiation biology. More recently, the veterinary and human radiation oncology fields have increasingly collaborated to achieve advancements in education, radiotherapy techniques, and trial networks. This review describes these advancements, including significant prior research findings and the evolution of the veterinary radiation oncology discipline. It concludes by describing how companion-animal models can help shape the future of human radiotherapy. Taken as a whole, this review suggests companion-animal cancers may become widely used for preclinical radiotherapy research. Full article

(This article belongs to the Special Issue The Future of Radiation Research in Cancers)

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