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Ultra-high dose rate radiotherapy (FLASH radiation) can naturally render normal tissues around the tumor tissue resistant to radiotherapy. In contrast, the tumor tissue remains sensitive to radiation under the same conditions. However, the effects of different fractions and dose rates on FLASH radiation remain unclear. This study aimed to determine the optimal dose rate and fraction of FLASH radiation for thoracic radiotherapy. Female Balb/c mice aged 6–8 weeks were irradiated with different dose rates (100 Gy/s or 250 Gy/s) and fractions (1, 2, or 4). Survival was observed in mice receiving 30Gy, with lung tissue examined for acute radiation damage 48 h post-radiation. Late radiation pneumonia and survival rates were monitored in mice irradiated with 20 Gy. The median overall survival (OS) was not reached on the 95th day for mice irradiated with 250 Gy/s FLASH radiation, while it was 89.5 days for those irradiated with 100 Gy/s (P = 0.0436). Mice irradiated with 30 Gy/2 Fr and 250 Gy/s FLASH had shorter median OS than those with 30 Gy/1F (P = 0.0132). However, there was no significant difference in OS between mice irradiated with 30 Gy/2 F and 30 Gy/4 F. Survival curves for mice receiving 20 Gy showed no significant difference in toxicity between different dose rates and fractions. FLASH radiation at 250 Gy/s reduced the incidence of acute radiation pneumonitis in mice compared to 100 Gy/s. Different fractions of irradiation influenced survival in mice, but they were only observed in acute radiation reactions and not chronic radiation reactions. Among the tested fraction methods, fraction 2 had the worst impact on the survival of mice, while fractions 1 and 4 showed similar effects and improved survival compared to fraction 2.

Inflammation and coagulation cascades are closely correlated with cancer occurrence and progression. This study investigated the prognostic value of the combination of plasma fibrinogen level and neutrophil-to-lymphocyte ratio (F-NLR) in patients with upper tract urothelial carcinoma (UTUC). The predictive ability of the F-NLR for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) was initially established and then further validated in patients who underwent radical nephroureterectomy for UTUC. As a result, patients were divided into three groups following the establishment of cut-off values for the NLR (≥2.53 vs.

PurposeGiven the unique features of the liver, it is necessary to combine immunotherapy with other therapies to improve its efficacy in patients of advanced cancer with liver metastases (LM). High-intensity focused ultrasound (HIFU) ablation is now widely used in clinical practice and can enhanced immune benefits. The study is intended to prospectively evaluate the safety and clinical feasibility of HIFU ablation in combination with systemic immunotherapy for patients with liver metastases.MethodsThe study enrolled 14 patients with LM who received ultrasound-guided HIFU ablation combined with immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein 1 (anti-PD-1 agents manufactured in China) at Mianyang Central Hospital. Patients were followed up for adverse events (AEs) during the trial, using the CommonTerminology Criteria for Adverse Events v5.0(CTCAE v5.0) as the standard. Tumour response after treatment was assessed using computerized tomography.ResultsThe 14 patients (age range, 35-84 years) underwent HIFU ablation at 19 metastatic sites and systemic immunotherapy. The mean lesion volume was 179.9 cm3 (maximum: 733.1 cm3). Median follow-up for this trial was 9 months (range: 3-21) months. The study is clinically feasible and acceptable to patients.ConclusionThis prospective study confirmed that HIFU combined with immunotherapy is clinically feasible and safe for treating liver metastases.

Introduction: This study aimed to compare the efficacy and safety of docetaxel + trastuzumab + pertuzumab and docetaxel + carboplatin + trastuzumab + pertuzumab for treating HER2-positive breast cancer. Method: HER2-positive breast cancer from patients diagnosed between January 2020 and September 2022 were included in this retrospective study. Docetaxel + trastuzumab + pertuzumab or docetaxel + carboplatin + trastuzumab + pertuzumab was selected as the neoadjuvant regimen. The primary endpoint was a complete pathological remission rate. Secondary endpoints were toxicity during neoadjuvant treatment, adjustment of the neoadjuvant therapy scheme, and adjuvant medication. Result: A total of 81 patients were included in this study (38 in the docetaxel + carboplatin + trastuzumab + pertuzumab treatment group and 43 in the docetaxel + trastuzumab + pertuzumab group). The complete pathological remission rates in the docetaxel + carboplatin + trastuzumab + pertuzumab and docetaxel + trastuzumab + pertuzumab groups were 44.7% (95% confidence interval: 30.2%-60.3%) and 51.2% (95% confidence interval: 36.8%-65.4%), respectively. The incidence of grade 3 or higher toxicity in the docetaxel + carboplatin + trastuzumab + pertuzumab group was significantly higher than that in the docetaxel + trastuzumab + pertuzumab group (68.4% vs 39.5%, P = .009). Neutropenia and asthenia were the most common grade 3 or higher toxicities. The incidence of neoadjuvant scheme adjustment was significantly higher in the docetaxel + carboplatin + trastuzumab + pertuzumab group than in the docetaxel + trastuzumab + pertuzumab group (26.3% vs 7.0%, P = .039). The proportion of patients who received

Ultra-high dose rate radiotherapy (FLASH-RT) is an external beam radiotherapy strategy that uses an extremely high dose rate (≥40 Gy/s). Compared with conventional dose rate radiotherapy (≤0.1 Gy/s), the main advantage of FLASH-RT is that it can reduce damage of organs at risk surrounding the cancer and retain the anti-tumor effect. An important feature of FLASH-RT is that an extremely high dose rate leads to an extremely short treatment time; therefore, in clinical applications, the steps of radiotherapy may need to be adjusted. In this review, we discuss the selection of indications, simulations, target delineation, selection of radiotherapy technologies, and treatment plan evaluation for FLASH-RT to provide a theoretical basis for future research.

FLASH radiotherapy (FLASH-RT) is a novel radiotherapy technology defined as ultra-high dose rate (≥ 40 Gy/s) radiotherapy. The biological effects of FLASH-RT include two aspects: first, compared with conventional dose rate radiotherapy, FLASH-RT can reduce radiation-induced damage in healthy tissue, and second, FLASH-RT can retain antitumor effectiveness. Current research shows that mechanisms of the biological effects of FLASH-RT are related to oxygen. However, due to the short time of FLASH-RT, evidences related to the mechanisms are indirect, and the exact mechanisms of the biological effects of FLASH-RT are not completely clear and some are even contradictory. This review focuses on the mechanisms of the biological effects of FLASH-RT and proposes future research directions.

Radiation enteritis (Re) is one of the most common complications of radiation therapy for abdominal tumors. The efficacy of cancer treatment by radiation is often limited by the side effects of Re. Re can be acute or chronic. Treatment of acute Re is essentially symptomatic. However, chronic Re usually requires surgical procedures. The underlying mechanisms of Re are complex and have not yet been elucidated. The purpose of this review is to provide an overview of the pathogenesis of Re. We reviewed the role of intestinal epithelial cells, intestinal stem cells (ISCs), vascular endothelial cells (ECs), intestinal microflora, and other mediators of Re, noting that a better understanding of the pathogenesis of Re may lead to better treatment modalities.

Abstract Objective Previous work has demonstrated that metastases are not uniformly distributed across the brain. This study aims to determine there are low-risk brain metastasis (BM) areas that may be avoided during whole-brain radiotherapy (WBRT) to reduce neurocognitive toxicity. Methods Clinical and magnetic resonance imaging (MRI) data of 991 metastases in 192 patients with advanced cancer were analyzed retrospectively. Eleven anatomically defined regions of interest (ROIs) were contoured, and the locations of the BMs were recorded. Using the same definition, ROIs were contoured in 20 healthy volunteers.The proportions of patients with BMs in different ROIs, proportion of BMs, and proportion of different ROI volumes relative to the total volume were calculated. Results The proportion of observed BMs was lower than expected in the brainstem, insula, diencephalon and internal structures, corpus callosum, and pituitary gland. The proportion of BMs was significantly higher than expected in the parietal lobe, occipital lobe, and cerebellum. For those patients with single BM, there was very low rate of low-risk ROIs involvement (0%), with 2–4 BMs, 6–13% of the patients had low-risk ROIs involvement, with ≥5 BMs, significant (> 30%) of the patients had low-risk ROIs involvement. Conclusion The brainstem, insula, diencephalon and internal structures, corpus callosum, and pituitary gland demonstrate low risk for metastatic involvement. Involvement of low risk areas occurs in patients with more than 1 BM.

The combination of hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been confirmed as an important risk biomarker in several cancers. Hence, we aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). We retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC in this study. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic (ROC) curve analysis. The relationship between postoperative survival outcomes and preoperative HALP level was assessed using Kaplan-Meier analysis and Cox regression analysis. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP

The prognosis of advanced malignant tumors is very poor, and effective treatment is limited. Radioimmunotherapy (RIT) is a novel treatment method. However, its anti-tumor effect is relatively low in solid tumors, which is mainly due to the blood-tumor barrier preventing RIT from penetrating the tumor, resulting in an insufficient dose. Low-intensity ultrasound with microbubbles (USMB) has proven capable of opening the blood-tumor barrier. The combination of the two technologies may overcome the poor anti-tumor effect of RIT and promote the clinical application of RIT in solid tumors. In this article, we reviewed the current research status of RIT in the treatment of solid tumors and the opportunities and challenges of USMB combined with RIT.

The biological effects of radiation dose to organs at risk surrounding tumor target volumes are a major dose-limiting constraint in radiotherapy. This can mean that the tumor cannot be completely destroyed, and the efficacy of radiotherapy will be decreased. Thus, ways to reduce damage to healthy tissue has always been a topic of particular interest in radiotherapy research. Modern radiotherapy technologies such as helical tomotherapy (HT), intensity-modulated radiation therapy (IMRT), and proton radiotherapy can reduce radiation damage to healthy tissues. Recent outcomes of animal experiments show that FLASH radiotherapy (FLASH-RT) can reduce radiation-induced damage in healthy tissue without decreasing antitumor effectiveness. The very short radiotherapy time compared to that of conventional dose-rate radiotherapy is another advantage of FLASH-RT. The first human patient received FLASH-RT in Switzerland in 2018. FLASH-RT may become one of the main radiotherapy technologies in clinical applications in the future. We summarize the history of the development of FLASH-RT, its mechanisms, its influence on radiotherapy, and its future.

Radiotherapy is one of the most important treatments for brain metastasis (BM). This study aimed to assess whether whole-brain radiation therapy (WBRT) with simultaneous integrated boost (SIB) provided any therapeutic benefit compared to WBRT followed by stereotactic radiosurgery (SRS). Seventy-two consecutive cases of lung cancer with BM treated from January 2014 to June 2020 were analyzed retrospectively. Thirty-seven patients were treated with WBRT (30 Gy in 10 fractions) and SIB (45 Gy in 10 fractions), and 35 patients were treated with WBRT (30 Gy in ten fractions) followed by SRS (16–24 Gy according to the maximum tumor diameter). The primary endpoint was intracranial progression-free survival (PFS). The secondary endpoints were intracranial objective response (partial and complete responses), pattern of intracranial progression, overall survival (OS), and toxicity. The WBRT + SIB group had a significantly longer median intracranial PFS (9.1 vs. 5.9 months, P = 0.001) than the WBRT + SRS group. The intracranial objective response rate was 67.6% and 62.9% in the WBRT + SIB and in WBRT + SRS groups, respectively (P = 0.675). The incidence of progression outside the P-GTV in the WBRT + SIB group was significantly lower than that in the WBRT + SRS group (39.4% vs. 75.0%, P = 0.004). The median OS was 24.3 and 20.3 months in the WBRT + SIB and WBRT + SRS groups, respectively (P = 0.205). There was no significant difference in the incidence of grade 3 or worse adverse reactions between the two groups. Compared to treatment with WBRT + SRS, that with WBRT + SIB for BM appeared to contribute to local control.

Cancer-associated inflammation, activation of coagulation cascades, and malnutrition are closely related to the prognosis of patients with malignancy, including renal cell carcinoma (RCC). This study aimed to investigate the prognostic value of a combination of preoperative plasma fibrinogen, prognostic nutritional index, and monocyte-to-lymphocyte ratio (Fib-PNI-MLR) in patients with non-metastatic RCC undergoing nephrectomy. We retrospectively collected medical data from 829 of the 1,019 cases of RCC. The optimal cutoff values of fibrinogen (≥3.54 vs.

Abstract Background Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. Methods This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. Results In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. Conclusion The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.

Background. This study aimed to evaluate the efficacy and safety of anlotinib combined with S-1 as a third- or later-line treatment for patients with stage IV non-small cell lung cancer (NSCLC). Anlotinib was approved in 2018 by the Chinese Food and Drug Administration (FDA) as a third-line treatment for patients with refractory advanced NSCLC and is under study in the U.S. and Europe. Methods. Simon's phase II clinical trial design with an α error of 5% and a power β of 80% was used, anticipating a 10% objective response rate (ORR) of anlotinib and a 30% ORR of anlotinib combined with S-1; the required sample size was 29. A total of 29 patients were enrolled in the clinical trial. Patients were treated with anlotinib plus S-1 over a 21-day treatment course until disease progression or unacceptable toxic effects. If the efficacy was assessed as stable disease, partial response, or complete response after six cycles, anlotinib was maintained until disease progression or death. The primary endpoint was the objective response rate. Somatic mutations were not required for study enrollment. Results. The median follow-up time was 11.1 months. Objective responses were observed in 11 of 29 (37.9%) patients making up the intention-to-treat population, which reached the target primary endpoint of 30% ORR. The median overall and progression-free survival were 16.7 and 5.8 months, respectively. The most common grade 3 adverse events (AEs) were gastrointestinal, including nausea, vomiting and diarrhea, fatigue, and hypertension. No grade 4 treatment-related AEs or treatment-related deaths occurred. Conclusion. The combination of anlotinib with S-1 in the third- or later-line treatment of stage IV NSCLC shows promising antitumor activity and manageable toxicity in patients with NSCLC; phase III trials will be planned in the future. [ABSTRACT FROM AUTHOR]