Technological Advances In Radiotherapy Research Articles

Treatment of extranodal NK/T-cell lymphoma: From past to future.

Extranodal NK/T-cell lymphoma (ENKTCL) is the most common subtype of T/NK-cell lymphoma in Asia and Latin America, but very rare in North American and Europe. Patient survival has improved significantly over the past two decades. However, standard treatment has not yet been established, although dozens of prospective trials have been conducted. To help understand how the treatment of ENKTCL has evolved in the past and what trends lie ahead, we have comprehensively reviewed the treatment of this aggressive malignancy, with a particular focus on neglected or unanswered issues, such as the optimal staging method, the best partner of asparaginase (Asp), the individualized administration of Asp, the preferred sequence of CT and RT and so on. Overall, the 5-year overall survival (OS) of patients with Ann Arbor stage I/II disease increased from < 50% in the early 20th century to > 80% in recent years, and the median OS of patients with Ann Arbor stage III/IV disease increased from < 1 year to more than 3 years. The improvement in patient survival is largely attributable to advances in radiation technology and the introduction of Asp and anti-PD-1/PD-L1 immunotherapy into practice. Radiotherapy is essential for patients with early-stage disease, while Asp-based chemotherapy (CT) and PD-1/PD-L1 inhibitors significantly improved the prognosis of patients with advanced-stage disease. ENKTCL management is trending toward simpler regimens, less toxicity, and higher efficacy. Novel drugs, such as manufactured T cells, monoclonal antibodies, and small molecule inhibitors, are being intensively investigated. Based on the fact that ENKTCL is highly resistant to cytotoxic drugs except Asp, and aggressive CT leads to higher toxicity rather than better outcomes, we recommend it is unnecessary to expend additional resources to compare different combinations of Asp with cytotoxic agents. Instead, more efforts should be made to optimize the use of Asp and immunotherapy to maximize efficacy and minimize toxicity, explore ways to overcome resistance to Asp and immunotherapy, identify novel treatment targets, and define subpopulations who may benefit more from specific treatments.

Radiotherapy of early‐stage breast cancer

AbstractBreast cancer is the most prevalent disease for women. With advances in breast cancer screening, most breast cancers are now diagnosed in the early stages. With knowledge of different subtypes and their behavior, breast cancer treatment has become more individualized. Radiation therapy as one of the mainstays of breast cancer treatment has also been evolving. This review attempts to provide a summary of the most influential clinical studies that have driven the technological advances in radiation therapy for early‐stage breast cancer.

Phytoradiotherapy to enhance cancer treatment outcomes with cannabidiol, bitter melon juice, and plant hemoglobin.

Despite technological advances in radiation therapy for cancer treatment, many patient populations still experience mediocre survival percentages, local control, and quality of life. Additionally, much of the world lacks access to expensive, modern treatment options. The need for innovative, cost-effective solutions that can improve patient treatment outcomes is essential. Phytomedicines have been shown to induce apoptotic tumor cell death, diminish tumor progression, reduce cancer incidence, alleviate harmful hypoxic conditions, and more. While an ample amount of research is available that characterizes many phytomedicines as having anti-cancer properties that increase tumor cell killing/control and mitigate the harmful side effects of radiation damage, little work has been done to investigate the synergistic effect of phytoradiotherapy: combining radiation treatment with phytomedicines. In this study, a protocol for testing the radiosensitizing effects of phytomedicines was validated and used to investigate the well-known plant based medicine cannabidiol (CBD) and the lesser-known medicinal fruit Bitter Melon. Additionally, based on its high concentration of plant hemoglobin which has been shown to abate hypoxia, the African-indigenous Justicia plant was tested in pancreatic adenocarcinoma mouse models. The studies reveal that these phytomedicines can effectively enhance tumor cell killing, minimize tumor growth, and prolong mice survival. There is certainly the need for additional research in this regard, however, phytoradiotherapy: the use of phytomedicines to enhance radiation therapy treatment outcomes, continues to show potential as a promising, innovative way to improve cancer care.

Radiotherapeutic Strategies to Overcome Resistance of Breast Cancer Brain Metastases by Considering Immunogenic Aspects of Cancer Stem Cells.

Breast cancer is the most diagnosed cancer in women, and symptomatic brain metastases (BCBMs) occur in 15-20% of metastatic breast cancer cases. Despite technological advances in radiation therapy (RT), the prognosis of patients is limited. This has been attributed to radioresistant breast cancer stem cells (BCSCs), among other factors. The aim of this review article is to summarize the evidence of cancer-stem-cell-mediated radioresistance in brain metastases of breast cancer from radiobiologic and radiation oncologic perspectives to allow for the better interpretability of preclinical and clinical evidence and to facilitate its translation into new therapeutic strategies. To this end, the etiology of brain metastasis in breast cancer, its radiotherapeutic treatment options, resistance mechanisms in BCSCs, and effects of molecularly targeted therapies in combination with radiotherapy involving immune checkpoint inhibitors are described and classified. This is considered in the context of the central nervous system (CNS) as a particular metastatic niche involving the blood-brain barrier and the CNS immune system. The compilation of this existing knowledge serves to identify possible synergistic effects between systemic molecularly targeted therapies and ionizing radiation (IR) by considering both BCSCs' relevant resistance mechanisms and effects on normal tissue of the CNS.

Helical tomotherapy: advanced radiotherapy technology

Helical tomotherapy: advanced radiotherapy technology

Radiotherapy Induces Innate Immune Responses in Patients Treated for Prostate Cancers.

Radiotherapy is a curative therapeutic modality used to treat cancers as a single agent or in combination with surgery and chemotherapy. Advanced radiotherapy technologies enable treatment with large fractions and highly conformal radiation doses to effect free-radical damage to cellular DNA leading to cell-cycle arrest, cell death, and innate immune response (IIR) stimulation. To understand systemic clinical responses after radiation exposure, proteomic and metabolomic analyses were performed on plasma obtained from patients with cancer at intervals after prostate stereotactic body radiotherapy. Pathway and multivariate analyses were used to delineate molecular alterations following radiotherapy and its correlation with clinical outcomes. DNA damage response increased within the first hour after treatment and returned to baseline by 1 month. IIR signaling also increased within 1 hour of treatment but persisted for up to 3 months thereafter. Furthermore, robust IIR and metabolite elevations, consistent with an early proinflammatory M1-mediated innate immune activation, were observed in patients in remission, whereas patients experiencing prostate serum antigen-determined disease progression demonstrated less robust immune responses and M2-mediated metabolite elevations. To our knowledge, these data are the first report of longitudinal proteomic and metabolomic molecular responses in patients after radiotherapy for cancers. The data supports innate immune activation as a critical clinical response of patients receiving radiotherapy for prostate cancer. Furthermore, we propose that the observed IIR may be generalized to the treatment of other cancer types, potentially informing multidisciplinary therapeutic strategies for cancer treatment.

Harmonica consensus, controversies, and future directions in radiotherapy for pediatric Wilms tumors.

Radiotherapy (RT) is essential for multimodality treatment of pediatric renal tumors, particularly in higher-risk and metastatic disease. Despite decades of use, particularly for Wilms tumor, there remain controversies regarding RT indications, timing, dose, and targets. To align global management, we address these issues in this international HARMONIsation and CollAboration (HARMONICA) project. There are multiple knowledge gaps and opportunities for future research including: (1) utilization of advanced RT technologies, including intensity-modulated RT, proton beam therapy, combined with image-guided RT to reduce target volumes; (2) impact of molecular biomarkers including loss of heterozygosity at 1p, 16q, and 1q gain on RT indications; (3) mitigation of reproductive toxicity following RT; (4) promotion of RT late effects research; and (5) support to overcome challenges in RT utilization in low- and middle-income countries where 90% of the world's children reside. Here, we outline current status and future directions for RT in pediatric renal tumors.

The Proportion of Prostate Cancer Randomized Control Trials Involving Radiation Therapy over Time

<h3>Purpose/Objective(s)</h3> As a cornerstone of oncologic treatment, radiation therapy (RT) is often incorporated in randomized controlled trials (RCTs). However, many trials may focus on systemic therapy rather than RT, despite numerous technological advances in RT. The primary purpose is to quantify the proportion of prostate cancer RCTs involving RT over time. <h3>Materials/Methods</h3> We conducted an analysis of all therapeutic prostate cancer RCTs from 2000 to 2021 in clinicaltrials.gov. We extracted all studies labeled condition or disease "Cancer," study type "Interventional." and other terms "prostate." We analyzed the percentage of trials with at least one RT arm. Study date was classified as 2000-2005, 2006-2010, 2011-2015, and 2016-2020. Covariates include study phase and patient enrollment. <h3>Results</h3> We extracted 1,104 prostate cancer RCTs of which 208 (19%) included at least one RT arm. Most prostate cancer RCTs were Phase 2 and Phase 3 trials (Table 1). The proportion of prostate cancer RT RCTs to all prostate cancer RCTs was 35/169 (21%), 28/242 (12%), 48/287 (17%), and 97/406 (24%) for 2000-2005, 2006-2010, 2011-2015, and 2016-2020, respectively. The median patient enrollment for RT prostate cancer RCTs decreased from 340 to 130 patients from 2000-2005 to 2016-2020. However, median patient enrollment for all prostate cancer RCTs remained stable at 141 to 120 patients from 2000–2005 to 2016-2020 (Table 1). <h3>Conclusion</h3> The proportion of RT prostate cancer RCTs remained stable over time, however, median patient enrollment decreased over time.

Chemical Overview of Gel Dosimetry Systems: A Comprehensive Review.

Advances in radiotherapy technology during the last 25 years have significantly improved both dose conformation to tumors and the preservation of healthy tissues, achieving almost real-time feedback by means of high-precision treatments and theranostics. Owing to this, developing high-performance systems capable of coping with the challenging requirements of modern ionizing radiation is a key issue to overcome the limitations of traditional dosimeters. In this regard, a deep understanding of the physicochemical basis of gel dosimetry, as one of the most promising tools for the evaluation of 3D high-spatial-resolution dose distributions, represents the starting point for developing new and innovative systems. This review aims to contribute thorough descriptions of the chemical processes and interactions that condition gel dosimetry outputs, often phenomenologically addressed, and particularly formulations reported since 2017.

Development of a Dual-Modality Gamma-ray/Fast Neutron Imaging System for Air Cargo Inspection

High-energy radiation sources have provided a strong security inspection capability using a non-invasive imaging system. The use of multiple radiation sources in one imaging system can also lead to a more powerful system that can classify various materials compared to using a single radiation source. The Advanced Radiation Technology Institute of Korea Atomic Energy Research Institute has developed an air cargo inspection system using multiple radiation sources such as fast neutrons and gamma-rays to classify the plastics, metals, and organics among various sample materials. The fast neutron beam with an energy of 14.1 MeV, generated using the D-T neutron generator, and the gamma-ray beam with an energy of 6 MeV, generated by an electron linear accelerator, are projected onto the vertically aligned scintillator-based radiation detectors. The neutron and gamma-ray images of a cargo container moved by a motorized linear translation stage are acquired, and the image data processing shows good material classification results. In this paper, we describe a multi-radiation imaging system for air cargo inspection and investigate its material classification capability using various sample materials.

A Review of PRESAGE Radiochromic Polymer and the Compositions for Application in Radiotherapy Dosimetry.

Recent advances in radiotherapy technology and techniques have allowed a highly conformal radiation to be delivered to the tumour target inside the body for cancer treatment. A three-dimensional (3D) dosimetry system is required to verify the accuracy of the complex treatment delivery. A 3D dosimeter based on the radiochromic response of a polymer towards ionising radiation has been introduced as the PRESAGE dosimeter. The polyurethane dosimeter matrix is combined with a leuco-dye and a free radical initiator, whose colour changes in proportion to the radiation dose. In the previous decade, PRESAGE gained improvement and enhancement as a 3D dosimeter. Notably, PRESAGE overcomes the limitations of its predecessors, the Fricke gel and the polymer gel dosimeters, which are challenging to fabricate and read out, sensitive to oxygen, and sensitive to diffusion. This article aims to review the characteristics of the radiochromic dosimeter and its clinical applications. The formulation of PRESAGE shows a delicate balance between the number of radical initiators, metal compounds, and catalysts to achieve stability, optimal sensitivity, and water equivalency. The applications of PRESAGE in advanced radiotherapy treatment verifications are also discussed.

Osteoradionecrosis of the jaws: A retrospective cohort study.

Radiotherapy (RT) combined with chemotherapy and surgery is the indicated treatment for head and neck cancers. Even with the advent of modern technological advances in RT and improved oral hygiene awareness, osteoradionecrosis (ORN) still remains as one of the most debilitating side effects of RT. This is a retrospective review assessing 72 patients aged over 18 years of age reporting in the Dental Department, for treatment of ORN from April 2010 to July 2019. Each patient was clinically examined and treated according to standard protocol. The stage of ORN was noted at the diagnosis and at follow-up. The demographic data, the tumor characteristics, and the treatment of patients were evaluated using descriptive statistics. At the time of diagnosis, 84.7% of the study population was found to have Epstein Type II chronic persistent nonprogressive lesions and 11.1% of the cohort had Type III active progressive lesions. Statistically significant correlation (P = 0.00) was found for ORN grade at diagnosis and at follow-up. ORN being a chronic pathology, stabilization of the disease was observed in 72.3% of cases. The resolution of the necrotic lesion and down staging of the disease was seen only in 2.8% of patients. ORN is mainly a chronic long standing pathology which is difficult to treat completely. Stabilization of symptoms and preventing further spread of the necrotic lesion should be the ultimate aim of the treatment to improve the quality of life of the patients.

Technological Advances in Radiotherapy: Current Status, Challenges and Promises

Synopsis: Technology has a pivotal role in the development of radiotherapy. In the last few decades, technological advancement has hugely improved the accuracy and safety in radiotherapy delivery. This includes the current use of conformal radiotherapy, intensity modulated radiotherapy, image-guided radiotherapy, and adaptive radiotherapy. In addition, artificial intelligence (AI) has recently been utilized to address different needs of radiotherapy planning. These AI technologies aim to reduce the trial-and-error planning process and guarantee quality of plans. They are also capable of mimicking human planners’ decision-making process during the iterative adjustment of plan optimization to increase efficiency. On top of all these current technological advances, the fight against cancer for better treatment outcomes has been a major challenge. One of the possible ways to address the challenge could be the development of personalized and precision medicine, which will allow us to carefully select patients according to the features of their tumor and to individually predict the risk of toxicity. Ongoing research studies using radiomics could be a promise that allow us to work towards the goal of providing precision care in radiotherapy for further improvement of cancer treatment in future.

Technological Advances in Radiotherapy: Current Status, Challenges and Promises

Synopsis: The improvement in imaging, planning and treatment delivery have enabled us to give the accurate and precise radiation dose to the target volume and spare the surrounding normal tissues. Advanced multi-modality diagnostic imaging with CT, MRI, and PET are the routine for target contouring. The technology of IGRT works as an essential role for accuracy and precision dose delivery, especially with real-time imaging. The development of computer software moves 3D technique to the advanced era, such as IMRT and VMAT. Modern treatment planning with knowledge-based plans can improve the planning consistency. The most popular radiotherapy machine is Linac, however, proton has gained particular interest as an alternative because of the dosimetric advantage.

Brain metastasis: Recent treatment modalities and future-perspectives.

With the advent of novel systemic therapies, such as molecular targeted therapy and immune checkpoint inhibitors, the treatment of advanced-stage cancer is markedly transitioning. The treatment for brain metastasis is influenced by these new therapies. Moreover, the frequency of brain metastasis is associated with cancer genetics. Since conventional cytotoxic chemotherapeutic drugs cannot easily cross the brain-blood barrier, radiotherapy plays a major role in the management of brain metastasis. Whole-brain radiotherapy (WBRT) has been frequently used, especially for multiple metastatic brain tumors; however, late adverse effects on cognitive function are a significant clinical problem of WBRT in patients with an otherwise good prognosis and overall survival rate. Some novel systemic agents are effective against brain metastasis. Moreover, advances in radiotherapy technology have made it possible to deliver optimal radiation doses to patients with brain metastasis, with fewer adverse events. Brain metastasis has a significant impact on the quality of life of patients with advanced-stage cancer; therefore, its appropriate management is an important factor in the comprehensive treatment of cancer.

Radiation-induced cardiac dysfunction: Practical implications.

Radiation-induced cardiac dysfunction is a critical healthcare concern facing survivors of thoracic cancers treated with radiation therapy. Despite cardiac-sparing advances in radiation therapy delivery, many patients with thoracic cancers receiving modern radiation therapy will still have incidental radiation exposure to the heart. Therefore, it is imperative that cardiovascular healthcare providers take appropriate measures to prevent, screen, and manage radiation-induced cardiac dysfunction in patients with a history of thoracic radiation therapy. In this review, we aim to provide healthcare providers with foundational information about radiation-induced cardiac pathophysiology and a chronology of advances in radiation technology. Subsequently, we provide an up-to-date review of treatment- and host-related factors that can influence a patient's risk for radiation-induced cardiac dysfunction. Finally, we culminate our discussion by detailing current screening and management guidelines to aid healthcare providers in caring for their patients with a history of thoracic radiation therapy.

Ablative Radiotherapy (ART) for Locally Advanced Pancreatic Cancer (LAPC): Toward a New Paradigm?

Locally advanced pancreatic cancer (LAPC) represents a major urgency in oncology. Due to the massive involvement of the peripancreatic vessels, a curative-intent surgery is generally precluded. Historically, LAPC has been an indication for palliative systemic therapy. In recent years, with the introduction of intensive multi-agent chemotherapy regimens and aggressive surgical approaches, the survival of LAPC patients has significantly improved. In this complex and rapidly evolving scenario, the role of radiotherapy is still debated. The use of standard-dose conventional fractionated radiotherapy in LAPC has led to unsatisfactory oncological outcomes. However, technological advances in radiation therapy over recent years have definitively changed this paradigm. The use of ablative doses of radiotherapy, in association with image-guidance, respiratory organ-motion management, and adaptive protocols, has led to unprecedented results in terms of local control and survival. In this overview, principles, clinical applications, and current pitfalls of ablative radiotherapy (ART) as an emerging treatment option for LAPC are discussed.

Association of Treatment Advances With Survival Rates in Pediatric Patients With Nasopharyngeal Carcinoma in China, 1989-2020

Advanced techniques and treatment methods have been found to be associated with improved survival rates in adults with nasopharyngeal carcinoma (NPC); however, not much is known about associations in pediatric patients. To investigate whether advanced imaging diagnosis, radiotherapy (RT) technology, and treatment modality are associated with survival in pediatric patients with NPC. In this retrospective cohort study, 810 pediatric patients ages 21 years and younger with nonmetastatic NPC diagnosed from 1989 to 2020 at a single cancer center in China were included. Data were analyzed from April through December 2021. Patients were divided into 3 groups by initial treatment date (ie, 1989-2002, 2003-2011, and 2012-2020). Associations between advances in technology and treatment and survival were investigated. Comparisons of advances vs older technology and treatments included those in imaging diagnosis (magnetic resonance imaging [MRI] vs computed tomography [CT] and positron emission tomography [PET]-CT with MRI vs CT), radiotherapy (RT) techniques (intensity-modulated RT [IMRT] or TomoTherapy [TOMO] vs 2-dimensional conventional radiotherapy [2D-CRT] or 3-dimensional conventional radiotherapy [3D-CRT]), and treatment methods (concurrent chemoradiotherapy [CCRT] vs RT alone, induction chemotherapy [IC] with CCRT vs RT alone, and CCRT or RT with adjuvant chemotherapy [AC] vs RT alone). The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), distant metastasis-free survival, and locoregional recurrence-free survival. Cox and competing-risks regression were used to estimate hazard ratios (HRs) and 95% CIs for associations between variables and survival. Among 810 pediatric patients with NPC, the median (IQR) age was 18 (15-20) years, and there were 577 [71.2%] male patients. This included 122 patients in the 1989 to 2002 period, 212 patients in the 2003 to 2011 period, and 476 patients in the 2012 to 2020 period. The 5-year PFS and OS rates increased, respectively, from 65.9% (95% CI, 56.6%-73.7%) and 69.9% (95% CI, 60.7%-77.4%) in 1989 to 2002 to 79.8% (95% CI, 73.7%-84.7%) and 86.2% (95% CI, 80.6%-90.3%) in 2003 to 2011, then 88.1% (95% CI, 84.2%-91.1%) and 95.0% (95% CI, 91.5%-97.0%) in 2012 to 2020. The 5- year cumulative incidence of distant metastasis rate was similar in the 3 periods (1989-2002: 11.7% [95% CI, 7.0%- 19.4%]; 2003-2011: 18.0% [95% CI, 13.4%-24.0%]; 2012-2020: 10.4% [95% CI, 7.6%-14.1%], while the 5-year cumulative incidence of locoregional recurrence rate decreased from 22.5% (95% CI, 15.9%-31.3%) in the first period to 2.9% (95% CI, 1.3%-6.3%) in the second period, remaining stable in the third period, at 4.3% (95% CI, 2.4%-7.6%). Advances in imaging diagnosis (MRI vs CT: hazard ratio [HR], 0.25 [95% CI, 0.17-0.38]; PET-CT with MRI vs CT: HR, 0.41 [95% CI, 0.27-0.62]), radiotherapy techniques (IMRT or TOMO vs 2D-CRT or 3D-CRT: HR, 0.42 [95% CI, 0.30-0.59]), and treatment methods (CCRT vs RT alone: HR, 0.55 [95% CI, 0.32-0.96]; IC with CCRT vs RT alone: HR, 0.59 [95% CI, 0.38-0.91]; CCRT or RT with AC vs RT alone: HR, 0.48 [95% CI, 0.25-0.91]) were associated with improved PFS. This study found that advanced techniques and treatment methods were associated with improved survival rates in pediatric patients with NPC, but distant failure remained a key challenge.

MR-guided radiotherapy for prostate cancer: state of the art and future perspectives.

Advances in radiotherapy technology have increased precision of treatment delivery and in some tumour types, improved cure rates and decreased side effects. A new generation of radiotherapy machines, hybrids of an MRI scanner and a linear accelerator, has the potential to further transform the practice of radiation therapy in some cancers. Facilitating superior image quality and the ability to change the dose distribution online on a daily basis (termed “daily adaptive replanning”), MRI-guided radiotherapy machines allow for new possibilities including increasing dose, for hard to treat cancers, and more selective sparing of healthy tissues, where toxicity reduction is the key priority.These machines have already been used to treat most types of cancer, although experience is still in its infancy. This review summarises the potential and current evidence for MRI-guided radiotherapy, with a predominant focus on prostate cancer. Current advantages and disadvantages are discussed including a realistic appraisal of the likely potential to improve patient outcomes. In addition, horizon scanning for near-term possibilities for research and development will hopefully delineate the potential role for this technology over the next decade.

Hypofractionated Radiation: Understanding the Modality and Impact on Patient Outcomes .

Radiation therapy has been used as a method to treat cancer since the early 1900s (Gianfaldoni et al., 2017). As of 2020, radiation continues to be a common treatment modality received by 50%-70% of patients with cancer at some point during the course of treatment (Peng et al., 2020). Numerous advances in radiation technology have occurred since its initial discovery, yet the goal of radiation remains the same. While chemotherapy is a systemic treatment, radiation therapy is designed to locally treat a malignancy. Unlike chemotherapy, radiation uses high-energy photon beams (x-ray or gamma rays), or charged particles (electrons or protons), to target specific locations of the body (Gianfaldoni et al., 2017). The damage to the DNA of the cells in the targeted region leads to eventual cell death, while allowing healthy cells outside of the targeted field to remain unaffected. Although toxicities occur, patients often experience fewer side effects during radiation therapy compared to chemotherapy because of its targeted approach. Advances in technology have led to better opportunities for targeting smaller areas of the body, reducing the potential for side effects (Garibaldi et al., 2017). In addition, radiation can be divided into larger doses to be given once a day, or less often, and is sometimes used as a shorter course of treatment. This is known as hypofractionated radiation. This article will explain the differences in radiation therapy modalities, focusing on hypofractionation and its benefits to patients.