Radiotherapy Modalities Research Articles

The concomitant of non-classical stereotactic body radiotherapy with tislelizumab based on multidisciplinary modalities for leiomyosarcoma: A case report.

Stereotactic body radiotherapy (SBRT) and immune checkpoint inhibitors (ICIs) could obtain a certain synergistic effect on bone and soft tissue sarcoma (BSTS). Given its low radiosensitivity, BSTS usually require an irradiation dose >65 Gy to achieve local control. Herein, we developed a non-classical SBRT technique called "onion-shaped simultaneous boost (OSB)," and reported a patient with prostatic leiomyosarcoma which received non-classical SBRT and other systemic treatments. In the case, a 49-year-old male patient was diagnosed with prostatic leiomyosarcoma in November 2018. In the radiotherapy plans, the maximum doses of the targets were more than 65 Gy, while the doses of the organs at risk (OARs) were strictly limited. After receiving radiotherapy, ICI, and other multidisciplinary modalities, the patient achieved partial response (PR). In this clinical case, we have observed that the OSB technique, which employs an increased per-fraction radiotherapy dose without the need to match the single-fraction doses typical of conventional SBRT, effectively enhances the therapeutic impact on leiomyosarcoma without an increase in radiotherapy-related side effects. By integrating the OSB technique with a multidisciplinary array of antineoplastic strategies, we can more effectively manage sarcomas in clinical practice.

Proton Radiation Therapy: A Systematic Review of Treatment-Related Side Effects and Toxicities.

Cancer is the second leading cause of death worldwide. Around half of all cancer patients undergo some type of radiation therapy throughout the course of their treatment. Photon radiation remains (RT) the most widely utilized modality of radiotherapy despite recent advancements in proton radiation therapy (PBT). PBT makes use of the particle's biological property known as the Bragg peak to better spare healthy tissue from radiation damage, with data to support that this treatment modality is less toxic than photon RT. Hence, proton radiation dosimetry looks better compared to photon dosimetry; however, due to proton-specific uncertainties, unexpected acute, subacute, and long-term toxicities can be encountered. Reported neurotoxicity resulting from proton radiation treatments include radiation necrosis, moyamoya syndrome, neurosensory toxicities, brain edema, neuromuscular toxicities, and neurocognitive toxicities. Pulmonary toxicities include pneumonitis and fibrosis, pleural effusions, and bronchial toxicities. Pericarditis, pericardial effusions, and atrial fibrillations are among the cardiac toxicities related to proton therapy. Gastrointestinal and hematological toxicities are also found in the literature. Genitourinary toxicities include urinary and reproductive-related toxicities. Osteological, oral, endocrine, and skin toxicities have also been reported. The side effects will be comparable to the ones following photon RT, nonetheless at an expected lower incidence. The toxicities collected mainly from case reports and clinical trials are described based on the organs affected and functions altered.

Adaptive stereotactic radiosurgery for cerebral metastases of non-small cell lung cancer: a retrospective study

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a common cause of brain metastases (BM). Adaptive stereotactic radiosurgery (ASRS) may be a useful option in the treatment of patients with large unresectable brain metastases (BM), but to date there are only a limited number of studies evaluating the effectiveness of this method.OBJECTIVE: To analyze the effectiveness of ASRS in patients with large BM NSCLC not subject to surgical resection.MATERIAL AND METHODS: We retrospectively analyzed data from 37 patients suffering from NSCLC with 45 large (>2 cm in diameter, volume >4 cm3) unresectable BM treated with the Gamma Knife Perfexion model using two- and three-fraction ASRS. Of these, 14 foci (31.1%) were metastases of squamous cell lung cancer, 31 (68.9%) were metastases of adenocarcinoma. The median volume of lesions treated with ASRS was 9.8 (range 4.6–30.6 cm3). The dynamics of volume changes between fractions and the cumulative incidence of local relapses (CILR) were studied, and ROC analysis was performed for the tumor volume parameter. Intracranial progression-free survival (iPFS) and overall survival (OS) were assessed. Statistics: To establish statistical significance of differences for related variables, the Wilcoxon test for pairwise comparisons and the Friedman test for three or more groups were used. The Kaplan-Meier method was used to calculate local control, PFS, and OS rates. The log-rank test was used to compare survival data in two groups.RESULTS: The median follow-up period was 19.4 months. With two-fraction ASRS, the median volume of metastasis decreased by 28.6% by the second session, with three-fraction — by 40.0% by the third session. The 1-year and 2-year CILR rates were 8.6±6.1%, respectively; 26.1±12.3%. In ROC analysis, the area under the curve (AUC) for tumor volume was 0.80 (95% CI 0.6– 1.0) with an optimal cutoff of 18.5 cm3. The differences in CILR between the groups with metastasis volume <18.5 cm3 and ≥18.5 cm3 were statistically significant (p<0.001). Median iPFS was 8.3 (95% CI 5.9–10.7) months, 1-year iPFS was 33.5±8.1%;2-year — 7.8±5.2%. Median OS was 13.2 (95% CI 9.0–17.4) months; 1-year OS — 52.9±8.7%, 2-year — 22.4±8.8%.DISCUSSION: Using two- and three-fraction ASRS, we delivered doses to large BM sufficient for a high level of local control with an acceptable risk of neurotoxicity: 1-year local control was 91.4%; 2-year — 73.9%; the incidence of radionecrosis is 8.5%. A statistically significant effect of lesion volume ≥18.5 cm3 on the risk of local recurrence was found. The iPFS and OS indicators after ASRS can be considered satisfactory for this group of patients.CONCLUSION: ASRS is an effective and perhaps optimal strategy for the treatment of large unresectable BM in patients with NSCLC, but comparison with other modern radiotherapy modalities such as stereotactic hypofractionated radiotherapy and WBRT with simultaneous integrated boost is needed.

CYRAD: a translational study assessing immune response to radiotherapy by photons or protons in postoperative head and neck cancer patients through circulating leukocyte subpopulations and cytokine levels

BackgroundRadiotherapy has both immunostimulant and immunosuppressive effects, particularly in radiation-induced lymphopenia. Proton therapy has demonstrated potential in mitigating this lymphopenia, yet the mechanisms by which different types of radiation affect the immune system function are not fully characterized. The Circulating Immunes Cells, Cytokines and Brain Radiotherapy (CYRAD) trial aims to compare the effects of postoperative X-ray and proton radiotherapy on circulating leukocyte subpopulations and cytokine levels in patients with head and neck (CNS and ear nose throat) cancer.MethodsCYRAD is a prospective, non-randomized, single-center non interventional study assessing changes in the circulating leukocyte subpopulations and cytokine levels in head and neck cancer patients receiving X-ray or proton radiotherapy following tumor resection. Dosimetry parameters, including dose deposited to organs-at-risk such as the blood and cervical lymph nodes, are computed. Participants undergo 29 to 35 radiotherapy sessions over 40 to 50 days, followed by a 3-month follow-up. Blood samples are collected before starting radiotherapy (baseline), before the 11th (D15) and 30th sessions (D40), and three months after completing radiotherapy. The study will be conducted with 40 patients, in 2 groups of 20 patients per modality of radiotherapy (proton therapy and photon therapy). Statistical analyses will assess the absolute and relative relationship between variations (depletion, recovery) in immune cells, biomarkers, dosimetry parameters and early outcomes.DiscussionPrevious research has primarily focused on radiation-induced lymphopenia, paying less attention to the specific impacts of radiation on different lymphoid and myeloid cell types. Early studies indicate that X-ray and proton irradiation may lead to divergent outcomes in leukocyte subpopulations within the bloodstream. Based on these preliminary findings, this study aims to refine our understanding of how proton therapy can better preserve immune function in postoperative (macroscopic tumor-free) head and neck cancer patients, potentially improving treatment outcomes.Protocol versionVersion 2.1 dated from January 18, 2023.Trial registrationThe CYRAD trial is registered from October 19, 2021, at the US National Library of Medicine, ClinicalTrials.gov ID NCT05082961.

Unsupervised machine learning model for detecting anomalous volumetric modulated arc therapy plans for lung cancer patients.

Volumetric modulated arc therapy (VMAT) is a new treatment modality in modern radiotherapy. To ensure the quality of the radiotherapy plan, a physics plan review is routinely conducted by senior clinicians; however, this process is less efficient and less accurate. In this study, a multi-task AutoEncoder (AE) is proposed to automate anomaly detection of VMAT plans for lung cancer patients. The feature maps are first extracted from a VMAT plan. Then, a multi-task AE is trained based on the input of a feature map, and its output is the two targets (beam aperture and prescribed dose). Based on the distribution of reconstruction errors on the training set, a detection threshold value is obtained. For a testing sample, its reconstruction error is calculated using the AE model and compared with the threshold value to determine its classes (anomaly or regular). The proposed multi-task AE model is compared to the other existing AE models, including Vanilla AE, Contractive AE, and Variational AE. The area under the receiver operating characteristic curve (AUC) and the other statistics are used to evaluate the performance of these models. Among the four tested AE models, the proposed multi-task AE model achieves the highest values in AUC (0.964), accuracy (0.821), precision (0.471), and F1 score (0.632), and the lowest value in FPR (0.206). The proposed multi-task AE model using two-dimensional (2D) feature maps can effectively detect anomalies in radiotherapy plans for lung cancer patients. Compared to the other existing AE models, the multi-task AE is more accurate and efficient. The proposed model provides a feasible way to carry out automated anomaly detection of VMAT plans in radiotherapy.

Clinical outcomes analysis of image-guided brachytherapy as definitive treatment for inoperable endometrial cancer

ObjectivesThis study evaluates the efficacy and toxicity of image-guided brachytherapy combined with or without external beam radiotherapy (IGBT ± EBRT) as definitive treatment for patients with inoperable endometrial cancer (IOEC), in addition to establishing a risk classification to predict prognosis.MethodsFifty-one IOEC patients who underwent IGBT ± EBRT at Peking Union Medical College Hospital from January 2012 to December 2021 were retrospectively analyzed, of which 42 patients (82.4%) were treated with IGBT + EBRT and 9 patients (17.6%) with IGBT alone. Establishing risk classification based on FIGO 2009 staging and biopsy pathology, stage III/IV, non-endometrioid, or Grade 3 endometrioid cancer were included in the high-risk group (n = 25), and stage I/II with Grade 1–2 endometrioid cancer was included in the low-risk group (n = 26).ResultsThe median follow-up time was 58.0 months (IQR, 37.0–69.0). Clinical complete remission (CR) was achieved in 92.2% of patients after radiotherapy (n = 47). The cumulative incidences of locoregional and distant failure were 19.6% (n = 10) and 7.8% (n = 4), respectively. A total of 20 patients died (39.2%), including 10 cancer-related deaths (19.6%) and 10 comorbidity-related deaths (19.6%). The 5-year locoregional control (LRC), time to progression (TTP), overall survival (OS), and cancer-specific survival (CSS) were 76.9%, 71.2%, 59.4%, and 77.0%, respectively. No Grade 3 or above acute or late toxicities were reported. In univariate analysis, LRC, TTP, and CSS were significantly higher in the low-risk group than in the high-risk group (P < 0.05). After adjusting for age, number of comorbidities, radiotherapy modality, and chemotherapy, the low-risk group was still significantly better than the high-risk group in terms of LRC (HR = 6.10, 95% CI: 1.18–31.45, P = 0.031), TTP (HR = 8.07, 95% CI: 1.64–39.68, P = 0.010) and CSS (HR = 6.29, 95% CI: 1.19–33.10, P = 0.030).ConclusionsIGBT ± EBRT is safe and effective as definitive treatment for IOEC patients, achieving satisfactory locoregional control, favorable survival outcomes, and low toxicity. Risk classification based on FIGO 2009 staging and biopsy pathology is an independent prognostic factor for LRC, TTP, and CSS.

State opioid prescribing laws and associations with radiotherapy delays and radiotherapy completion.

122 Background: In July 2018, Missouri introduced a 7-day limit for initial opioid prescriptions, though there was an exemption for cancer-related pain. However, some worry that the exemptions may be inadequate for patients with cancer who experience cancer-related pain. Since some courses of radiotherapy can cause pain (eg, mucositis, esophagitis), appropriate opioid access is important for helping patients complete radiotherapy in a timely manner, which is associated with oncologic outcomes. Methods: Patients with cancer of all ages treated with radiotherapy from 2018-2019 at a large academic institution in Missouri were identified. More recent data were excluded due to the COVID-19 pandemic and Missouri Medicaid expansion. Trends over time in the proportion of missed/delayed radiotherapy fractions, incomplete radiotherapy courses, and a composite measure of excessive delays (≥5 days) or incomplete course were evaluated in linear and linear probability models. Additional analyses included patients from Illinois, an adjacent state without opioid prescribing legislation, and we subsequently performed difference-in-differences analyses comparing the outcomes from pre- to post- Missouri opioid legislation between the states. We conducted unadjusted analyses as well as analyses adjusted for age, sex, site, radiotherapy modality and fractions, as well as other covariates that could impact access to radiotherapy (ZIP code deprivation, distance from the facility, insurance status, and social work referral for unmet needs). Subgroup analyses focused on patients with head and neck cancer and lung cancer receiving definitive radiotherapy, who are at high risk of radiotherapy-related pain. Results: A total of 2613 and 1518 patients from Missouri and Illinois were identified, respectively. 4.7% of fractions were missed/delayed, 3.7% of patients did not complete treatment, and 8.1% of patients had either an incomplete course or excessive delays. There were no statistically significant increases (ie, worsening) in any outcome in any quarter after opioid policy implementation, and there were significant decreases in the composite outcome in multiple post-policy quarters in both unadjusted and adjusted analyses. In difference-in-differences analyses comparing trends over time with patients from Illinois, there were no significant associations of policy implementation with any of the outcomes. Results were similar in subgroup analyses for patients with head and neck and lung cancers. Conclusions: Missouri legislation limiting opioid prescribing for non-cancer-related pain was not associated with significant changes in a patient’s ability to undergo radiotherapy. Limitations of the study include evaluation of a single center in a single state and the lack of other intermediate outcomes important to patients including access to opioid medication itself, which we will examine in future work.

Stereotactic radiosurgery practice patterns for treatment of brain metastases: A large national cancer database study.

123 Background: Brain metastases (BM) portend high mortality rates. While whole brain radiation therapy (WBRT) is a commonly used treatment strategy for BM, stereotactic radiosurgery (SRS) has less neurocognitive toxicity with comparable survival. The objective of this study was to compare treatment practice patterns for SRS vs WBRT using a large national hospital database. Methods: The National Cancer Database (NCDB) was queried for patients ≥18 years treated with radiotherapy (RT) for a BM diagnosis between 2004-2020 and with known follow-up. Twelve cancers were included based on highest prevalence: breast, colorectal, kidney/bladder, liver, lung, lymphoma, melanoma, oral cavity, pancreas, prostate, and thyroid. Patients were grouped by first course RT modality (SRS vs WBRT) confirmed by fraction number (SRS: 1-5; WBRT: 5-15). Multivariable logistic regression assessed predictors of SRS as adjusted odds ratios (aOR) with 95% confidence intervals (95%CI). Analyses were adjusted for patient and cancer characteristics. Results: Of 112,232 patients with BM, 30,805 (27%) received SRS. Median age was 64 years. Most patients were White (84%), diagnosed in 2012-2020 (64%), with a higher income (56%), more education (55%), and Medicare/Medicaid (60%). The most common cancer treated with RT for BM was lung (85%). Patients were less likely to be treated with SRS if they were Korean (aOR=0.68; 95%CI=0.47-0.95), lower income (aOR=0.88; 95%CI=0.84-0.91), lower education (aOR=0.88; 95%CI=0.85-0.91), with Medicare/Medicaid (aOR=0.86; 95%CI=0.83-0.89) or no insurance (aOR=0.48; 95%CI=0.44-0.53), at a Midwest hospital (aOR=0.79; 95%CI=0.76-0.83; vs Northeast), and at a community (aOR=0.31; 95%CI=0.28-0.33; vs academic) or comprehensive community cancer program (aOR=0.56; 95%CI=0.54-0.58). Patients were more likely to be treated with SRS if they were Asian Indian or Pakistani (aOR=1.41; 95%CI =1.08-1.85), older (aOR=1.01; 95%CI=1.01-1.01), diagnosed in 2012-2020 (aOR=3.92; 95%CI=3.78-4.07; vs 2004-2011), lived farther from the hospital (aOR=1.00; 95%CI=1.00-1.00), and received chemotherapy (aOR=1.17; 95%CI=1.13-1.21). Conclusions: In one of the largest BM studies with over 110,000 US patients, disparities in SRS treatment patterns were identified. On adjusted analysis, SRS was less likely to be used for patients who were lower income, lower educational attainment, without private insurance, and treated at community centers. The data highlight populations with cancer and BM who may benefit from increased access to SRS.

Patterns of Care for Brain Metastases in Asia: A Real-World Survey Conducted by the Federation of Asian Organizations for Radiation Oncology.

To report the patterns of care for brain metastases (BMs) in the Federation of Asian Organizations for Radiation Oncology (FARO). Overall, 37 questions were prepared. The survey was conducted online using Google Forms, and the URL was distributed to members of the FARO research committee. Radiation oncologists associated with FARO responded to the questionnaire between May 2023 and June 2023, and their answers were analyzed. Responses were received from 32 radiation oncologists in 13 countries participating in FARO. Twenty-six physicians (81.3%) were affiliated with academic centers, and 22 (68.8%) were able to perform stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (fSRT) for BMs at their institution. The most typically used prognostic index for BM was the recursive partitioning analysis classification (17 physicians, 53.1%). The maximum number of BMs indicated for SRT/SRS was ≤three (11 physicians, 34.4%), whereas eight (25.0%) physicians answered for 6-10 BMs. The maximum size of BMs considered for SRS/fSRT was ≤3 cm (14 physicians, 43.8%), whereas nine (28.1%) answered that SRS/fSRT was preferred if the maximum size was >4 cm. When whole-brain radiotherapy (RT) was indicated, hippocampal avoidance and memantine usage were limited to 50.0% and 25.0% of patients, respectively. The most typical RT modality after BM resection was SRS/fSRT alone, regardless of whether the margin was positive (19 physicians, 59.4%) or negative (13 physicians, 40.6%). We report the survey results of the patterns of care for BMs in the FARO. This survey was conducted only among a limited number of FARO members. Since many respondents were affiliated with relatively large-scale academic centers, large-scale surveys, including community hospitals, are warranted for future initiatives.

Recent developments in the field of radiotherapy for the management of lung cancer.

Lung cancer has a poor prognosis, and further improvements in outcomes are needed. Radiotherapy plays an important role in the treatment of unresectable lung cancer, and there have been recent developments in the field of radiotherapy for the management of lung cancer. However, to date, there have been few reviews on the improvement in treatment outcomes associated with high precision radiotherapy for lung cancer. Thus, this review aimed to summarize the recent developments in radiotherapy techniques and indicate the future directions in the use of radiotherapy for lung cancer. Stereotactic body radiotherapy (SBRT) for unresectable stage I lung cancer has been reported to improve local control rates without severe adverse events, such as radiation pneumonitis. For locally advanced lung cancer, a combination of chemoradiotherapy and adjuvant immune checkpoint inhibitors dramatically improves treatment outcomes, and intensity-modulated radiotherapy (IMRT) enables safer radiation therapy with less frequent pneumonitis. Particle beam therapy, such as carbon-ion radiotherapy and proton beam therapy, has been administered as advanced medical care for patients with lung cancer. Since 2024, it has been covered under insurance for early stage lung cancer with tumors ≤ 5cm in size in Japan. In addition to chemotherapy, local ablative radiotherapy improves treatment outcomes in patients with oligometastatic stage IV lung cancer. A particular problem with radiotherapy for lung cancer is that the target location changes with respiratory motion, and various physical methods have been used to control respiratory motion. Recently, coronavirus disease has had a major impact on lung cancer treatment, and cancer treatment during situations, such as the coronavirus pandemic, must be performed carefully. To improve treatment outcomes for lung cancer, it is necessary to fully utilize evolving radiotherapy modalities, and the role of radiotherapy in lung cancer treatment is expected to increase.

Current views on mechanisms of the FLASH effect in cancer radiotherapy.

FLASH radiotherapy (FLASH-RT) is a new modality of radiotherapy that delivers doses with ultra-high dose rates. The FLASH effect was defined as the ability of FLASH-RT to suppress tumor growth while sparing normal tissues. Although the FLASH effect has been proven to be valid in various models by different modalities of irradiation and clinical trials of FLASH-RT have achieved promising initial success, the exact underlying mechanism is still unclear. This article summarizes mainstream hypotheses of the FLASH effect at physicochemical and biological levels, including oxygen depletion and free radical reactions, nuclear and mitochondria damage, as well as immune response. These hypotheses contribute reasonable explanations to the FLASH effect and are interconnected according to the chronological order of the organism's response to ionizing radiation. By collating the existing consensus, evidence and hypotheses, this article provides a comprehensive overview of potential mechanisms of the FLASH effect and practical guidance for future investigation in the field of FLASH-RT.

Interventional radiotherapy: CT-sim guided modern minimally invasive technique

The concept of interventional radiology was introduced in 1976 as a new diagnostic and therapeutic method, relying on image guidance, such as X-ray, ultrasound, computed tomography (CT), and magnetic resonance imaging. Its indications mainly include obstructive diseases, and to a lesser extent, malignant tumors. Radiotherapy (RT) plays a pivotal role in the comprehensive treatment of cancer. The advent of the CT simulator has significantly enhanced the precision of RT and improvement outcomes and accelerated the development of a series of diagnostic and RT modalities, including puncture biopsy, fiducial marker implantation, high-dose rate after-loading after-loading brachytherapy, and radioactive seed implantation. The innovative concept of image-guidance interventional RT, inspired by interventional radiology, extends the benefits to not only cancer diagnosis but also RT. The image-guidance interventional RT advances the field of RT by expanding its indications and connotation.

Bayesian networks in modeling leucocyte interplay following brain irradiation: A comprehensive framework

Background and ObjectiveUnderstanding the intricate interactions among leucocyte subpopulations following radiotherapy is crucial for advancing cancer research and immunology. Recently, interest in recent radiotherapy modalities, such as protons, has increased. Herein, we present a framework utilizing Bayesian networks to uncover these complex relationships via an illustrative example of brain irradiation in rodents. MethodsWe utilized data from 96 healthy C57BL/6 adult mice subjected to either X-ray or proton brain irradiation. Leucocyte subpopulations in the blood collected 12 hours after the final irradiated fraction were quantified. We employed Bayesian networks to detect causal interplay between physiological parameters, radiation variables and circulating leucocytes. The causal structure was learned via the use of the Bayesian information criterion as a scored criterion. Parameter estimation was performed to quantify the strength of the identified causal relationships. Cross-validation was used to validate our Bayesian network model's performance. ResultsIn the X-ray model, we discovered previously undisclosed interactions between NK-cells and neutrophils, and between monocytes and T-CD4+ cells. The proton model revealed an interplay involving T-CD4+ cells and neutrophils. Both X-rays and protons led to heightened interactions between T-CD8+ cells and B cells, indicating their significant role in orchestrating immune responses. Additionally, the proton model displayed strengthened interactions between T-CD4+ and T-CD8+ cells, emphasizing a dynamic and coordinated immune response post-irradiation. Cross-validation results demonstrated the robustness of the Bayesian network model in explaining data uncertainty. ConclusionThe use of Bayesian networks as tools for causal structure discovery has revealed novel insights into the dynamics of immune responses to radiation exposure.

Recent update of proton beam therapy for hepatocellular carcinoma: a systematic review and meta-analysis.

Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and metaanalysis to investigate the updated evidence of PBT for HCC. The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024. A total of 1,858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range, 41-100), and the median tumor size was 3.6 cm (range, 1.2-9.0). The median total dose ranged from 55 GyE to 76 GyE (median, 69). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91) and 86% (95% CI, 82-90), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66) and 46% (95% CI, 38-54), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiationinduced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively. The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.

The Potential for Targeting G2/M Cell Cycle Checkpoint Kinases in Enhancing the Efficacy of Radiotherapy.

Radiotherapy is one of the main cancer treatments being used for ~50% of all cancer patients. Conventional radiotherapy typically utilises X-rays (photons); however, there is increasing use of particle beam therapy (PBT), such as protons and carbon ions. This is because PBT elicits significant benefits through more precise dose delivery to the cancer than X-rays, but also due to the increases in linear energy transfer (LET) that lead to more enhanced biological effectiveness. Despite the radiotherapy type, the introduction of DNA damage ultimately drives the therapeutic response through stimulating cancer cell death. To combat this, cells harbour cell cycle checkpoints that enables time for efficient DNA damage repair. Interestingly, cancer cells frequently have mutations in key genes such as TP53 and ATM that drive the G1/S checkpoint, whereas the G2/M checkpoint driven through ATR, Chk1 and Wee1 remains intact. Therefore, targeting the G2/M checkpoint through specific inhibitors is considered an important strategy for enhancing the efficacy of radiotherapy. In this review, we focus on inhibitors of Chk1 and Wee1 kinases and present the current biological evidence supporting their utility as radiosensitisers with different radiotherapy modalities, as well as clinical trials that have and are investigating their potential for cancer patient benefit.

Immune effects of α and β radionuclides in metastatic prostate cancer.

External beam radiotherapy is used for radical treatment of organ-confined prostate cancer and to treat lesions in metastatic disease whereas molecular radiotherapy with labelled prostate-specific membrane antigen ligands and radium-223 (223Ra) is indicated for metastatic prostate cancer and has demonstrated substantial improvements in symptom control and overall survival compared with standard-of-care treatment. Prostate cancer is considered an immunologically cold tumour, so limited studies investigating the treatment-induced effects on the immune response have been completed. However, emerging data support the idea that radiotherapy induces an immune response in prostate cancer, but whether the response is an antitumour or pro-tumour response is dependent on the radiotherapy regime and is also cell-line dependent. In vitro data demonstrate that single-dose radiotherapy regimes induce a greater immune-suppressive profile than fractionated regimes; less is known about the immune response induced by molecular radiotherapy agents, but evidence suggests that these agents might induce an immune-suppressive systemic immune response, indicated by increased expression of inhibitory checkpoint molecules such as programmedcelldeath 1ligand 1 and 2, and that these changes could be associated with clinical response. Different radiotherapy modalities can induce distinct immune profiles, which can either activate or suppress immune-mediated tumour killing and the current preclinical models used for prostate cancer research are not yet optimal for studying the complexity of the radiotherapy-induced immune response.

Prediction of the treatment effect of FLASH radiotherapy with synchrotron radiation from theCircular Electron-Positron Collider (CEPC).

The Circular Electron-Positron Collider (CEPC) in China can also work as an excellent powerful synchrotron light source, which can generate high-quality synchrotron radiation. This synchrotron radiation has potential advantages in the medical field as it has a broad spectrum, with energies ranging from visible light to X-rays used in conventional radiotherapy, up to several megaelectronvolts. FLASH radiotherapy is one of the most advanced radiotherapy modalities. It is a radiotherapy method that uses ultra-high dose rate irradiation to achieve the treatment dose in an instant; the ultra-high dose rate used is generally greater than 40 Gy s-1, and this type of radiotherapy can protect normal tissues well. In this paper, the treatment effect of CEPC synchrotron radiation for FLASH radiotherapy was evaluated by simulation. First, a Geant4 simulation was used to build a synchrotron radiation radiotherapy beamline station, and then the dose rate that the CEPC can produce was calculated. A physicochemical model of radiotherapy response kinetics was then established, and a large number of radiotherapy experimental data were comprehensively used to fit and determine the functional relationship between the treatment effect, dose rate and dose. Finally, the macroscopic treatment effect of FLASH radiotherapy was predicted using CEPC synchrotron radiation through the dose rate and the above-mentioned functional relationship. The results show that the synchrotron radiation beam from the CEPC is one of the best beams for FLASH radiotherapy.

Surgically targeted radiation therapy versus stereotactic radiation therapy: A dosimetric comparison for brain metastasis resection cavities

BackgroundSurgically targeted radiation therapy (STaRT) with Cesium-131 seeds embedded in a collagen tile is a promising treatment for recurrent brain metastasis. In this study, the biological effective doses (BED) for normal and target tissues from STaRT plans were compared with those of external beam radiotherapy (EBRT) modalities. MethodsNine patients (n=9) with 12 resection cavities (RCs) who underwent STaRT (cumulative physical dose of 60 Gy to a depth of 5 mm from the RC edge) were replanned with CyberKnife® (CK), Gamma Knife® (GK), and intensity modulated proton therapy (IMPT) using an SRT approach (30 Gy in 5 fractions). Statistical significance comparing D95% and D90% in BED10Gy (BED10Gy95% and BED10Gy90%) and to RC + 0 to + 5 mm expansion margins, and parameters associated with radiation necrosis risk (V83Gy, V103Gy, V123Gy and V243Gy) to the normal brain were evaluated by a Wilcoxon-signed rank test. ResultsFor RC+0 mm, median BED10Gy90% for STaRT (90.1 Gy10, range: 64.1-140.9 Gy10) was significantly higher than CK (74.3 Gy10, range:59.3-80.4 Gy10, p=0.04), GK (69.4 Gy10, range: 59.8-77.1 Gy10, p=0.005), and IMPT (49.3 Gy10, range: 49.0-49.7 Gy10, p=0.003), respectively. However, for the RC+5 mm, the median BED10Gy90% for STaRT (34.1 Gy10, range: 22.2-59.7 Gy10) was significantly lower than CK (44.3 Gy10, range: 37.8-52.4 Gy10), and IMPT (46.6 Gy10, range: 45.1-48.5 Gy10), respectively but not significantly different from GK (34.1 Gy10, range: 22.8-47.0 Gy10). The median V243Gy was significantly higher in CK (11.7 cc, range: 4.7-20.1 cc), GK(6.2 cc, range: 2.3-11.9 cc) and IMPT (19.9 cc, range: 11.1-36.6 cc) compared to STaRT (1.1 cc, range: 0.0-7.8 cc) (p<0.01). ConclusionThis comparative analysis suggests the STaRT approach may treat recurrent brain tumors effectively via delivery of higher radiation doses with equivalent or greater BED up to at least 3 mm from the RC edge as compared to EBRT approaches.

Impact of proton versus photon adjuvant radiotherapy on overall survival in the management of skull base and spinal chordomas: a National Cancer Database analysis.

Chordomas are rare tumors that originate from undifferentiated remnants of the notochord. Currently, there are no established guidelines regarding the choice of adjuvant radiation modality for patients surgically treated for chordomas. Using a nationwide, multicenter database, the authors aimed to compare long-term survival outcomes associated with the use of proton or photon adjuvant therapy for the management of chordomas of skull base and spine. The National Cancer Database (NCDB) was queried for chordoma cases from 2004 to 2017. Patient, tumor, and treatment characteristics were extracted from the database. The primary outcome was overall survival (OS). Kaplan-Meier survival analyses were conducted to investigate differences in outcome on propensity score-matched cohorts of patients treated with proton or photon adjuvant radiotherapy. Of the 3490 patients available, 424 met the inclusion criteria for this study. In the prematching analysis, patients receiving adjuvant photon therapy were significantly older (median age 57.0 vs 45.0 years, p < 0.001) and were more commonly male (61% vs 43%, p < 0.001) compared with those receiving proton therapy. Races were equally distributed among radiotherapy modalities (p = 0.64). Patients with chordomas of the mobile spine or sacrum were less likely to receive proton compared with photon therapy (37% vs 58%). Patients receiving proton therapy were more often represented among private insurance holders (69% vs 52%, p < 0.001) as well as in the highest income quartile (52% vs 40%, p = 0.008). Patients traveled farther to receive proton, as opposed to photon, therapy (median 59.0 vs 34.9 miles, p < 0.001). On postmatching Kaplan-Meier analysis encompassing all chordoma cases, no difference in OS between photon and proton therapy was revealed (HR 0.75, 95% CI 0.39-1.44; p = 0.39). A Kaplan-Meier analysis only including patients with skull base chordomas reached similar results (HR 0.83, 95% CI 0.31-2.22; p = 0.71). In patients with spine chordomas, however, a significant difference was found, as proton therapy exhibited a superior OS over photon therapy (HR 0.28, 95% CI 0.09-0.81; p = 0.012). Based on this nationwide analysis, patients with private insurance and higher income were more likely to receive proton adjuvant radiotherapy, while those with spinal or sacral chordomas were less likely to receive this modality. Despite this disparity, an OS benefit was observed in patients with chordomas of the spine and sacrum who received adjuvant proton therapy, in comparison with a matched cohort of patients treated with photon therapy. Conversely, this advantageous outcome was not evident in cases of chordomas located at the skull base.

Bismuth nanoparticles-enhanced proton therapy: Concept and biological assessment

Proton therapy presents an appealing radiotherapy modality for the treatment of deeply-seated and unresectable tumors, but it still needs additional means to enhance the localization and efficiency of therapeutic action. Here we explore the use of elemental bismuth nanoparticles (Bi NPs) as sensitizers for proton therapy enhancement. Spherical Bi NPs were prepared by the method of pulsed laser ablation, followed by their coating with Pluronic polymer to stabilize them in a physiological environment. We observed efficient apoptotic cell death after proton irradiation at the Bragg peak, which was explained by high proton stopping power and low work function of Bi. The maximal effect was observed for 3 Gy radiation and 50 μg/mL NPs dose with 97 % inhibition of tumor cell clonogenic activity. The strong therapeutic effect was confirmed in vivo using aggressive Sa37 sarcoma tumors in mice. We observed 60 % inhibition of primary tumor growth with a decrease of metastatic potential in popliteal and axillary lymph nodes. Combined with X-ray contrast properties and radiosensitizing functionalities, the proposed concept of Bi NPs-enhanced proton therapy promises a major upgrade for cancer therapy.