Predicting the efficacy of radiotherapy for esophageal squamous cell carcinoma based on enhanced computed tomography radiomics and combined models.

Purpose: This study aimed to investigate the ability of enhanced computed tomography (CT)-based radiomics and dosimetric parameters in predicting response to radiotherapy for esophageal cancer. Methods: A retrospective analysis of 147 patients diagnosed with esophageal cancer was performed, and the patients were divided into a training group (104 patients) and a validation group (43 patients). In total, 851 radiomics features were extracted from the primary lesions for analysis. Maximum correlation minimum redundancy and minimum least absolute shrinkage and selection operator were utilized for feature screening of radiomics features, and logistic regression was applied to construct a radiotherapy radiomics model for esophageal cancer. Finally, univariate and multivariate parameters were used to identify significant clinical and dosimetric characteristics for constructing combination models. The area evaluated the predictive performance under the receiver operating characteristics (AUC) curve and the accuracy, sensitivity, and specificity of the training and validation cohorts. Results: Univariate logistic regression analysis revealed statistically significant differences in clinical parameters of sex (p=0.031) and esophageal cancer thickness (p=0.028) on treatment response, whereas dosimetric parameters did not differ significantly in response to treatment. The combined model demonstrated improved discrimination between the training and validation groups, with AUCs of 0.78 (95% confidence interval [CI], 0.69-0.87) and 0.79 (95% CI, 0.65-0.93) in the training and validation groups, respectively. Conclusion: The combined model has potential application value in predicting the treatment response of patients with esophageal cancer after radiotherapy.

Mechanisms of FLASH effect.

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.

How neutron scattering techniques benefit investigating structures and dynamics of monoclonal antibody.

Over the past several decades, great progresses have been made for the pharmaceutical industry of monoclonal antibody (mAb). More and more mAb products were approved for human therapeutics. This review describes the state of art of utilizing neutron scattering to investigate mAbs, in the aspects of structures, dynamics, physicochemical stability, functionality, etc. Firstly, brief histories of mAbs and neutron scattering, as well as some basic knowledges and principles of neutron scattering were introduced. Then specific examples were demonstrated. For the structure and structural evolution investigation of in dilute and concentrated mAbs solution, in situ small angle neutron scattering (SANS) was frequently utilized. Neutron reflectometry (NR) is powerful to probe the absorption behaviors of mAbs on various surfaces and interfaces. While for dynamic investigation, quasi-elastic scattering techniques such as neutron spin echo (NSE) demonstrate the capabilities. With this review, how to utilize and take advantages of neutron scattering on investigating structures and dynamics of mAbs were demonstrated and discussed.

A randomized controlled trial for evaluating pain response in patients with spinal metastases following local versus whole vertebral radiotherapy: study protocol for phase II clinical trial.

BACKGROUND: Patients with bone metastasis often experience severe pain that is difficult to control and seriously affects quality of life. Radiotherapy is an effective way to relieve pain in these patients. Currently, there is no standard recommended range of radiotherapy targets for vertebral metastasis. The effect of radiotherapy on pain relief varies among patients, and some patients with metastases have serious side effects. METHODS: This study aims to verify whether reducing the radiotherapy range for vertebral metastases can achieve the same effect as whole vertebral radiotherapy while minimizing side effects. Sixty-six patients with pain caused by vertebral metastasis were randomly divided into two groups. The study group is receiving partial vertebrae body radiotherapy at the regions of abnormal signal, suspected invasion, and adjacent subclinical focus of vertebral metastasis, and the control group is receiving the same dose of radiotherapy on whole vertebrae body where metastasis occurred. After radiotherapy, along-term follow-up of patients will determine pain relief and side effects. DISCUSSION: The expected results of this study are that local irradiation of vertebral metastases can achieve a palliative effect of pain control not less than total vertebral irradiation with fewer side effects. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (No: ChiCTR1900023401 ).

First demonstration of the FLASH effect with ultrahigh dose rate high-energy X-rays.

PURPOSE: This study aimed to evaluate whether high-energy X-rays (HEXs) of the PARTER (platform for advanced radiotherapy research) platform built on CTFEL (Chengdu THz Free Electron Laser facility) can produce ultrahigh dose rate (FLASH) X-rays and trigger the FLASH effect. MATERIALS AND METHODS: EBT3 radiochromic film and fast current transformer (FCT) devices were used to measure absolute dose and pulsed beam current of HEXs. Subcutaneous tumor-bearing mice and healthy mice were treated with sham, FLASH, and conventional dose rate radiotherapy (CONV), respectively to observe the tumor control efficiency and normal tissue damage. RESULTS: The maximum dose rate of HEXs of PARTER was up to over 1000 Gy/s. Tumor-bearing mice experiment showed a good result on tumor control (p < 0.0001) and significant difference in survival curves (p < 0.005) among the three groups. In the thorax-irradiated healthy mice experiment, there was a significant difference (p = 0.038) in survival among the three groups, with the risk of death decreased by 81% in the FLASH group compared to that in the CONV group. The survival time of healthy mice irradiated in the abdomen in the FLASH group was undoubtedly higher (62.5% of mice were still alive when we stopped observation) than that in the CONV group (7 days). CONCLUSION: This study confirmed that HEXs of the PARTER system can produce ultrahigh dose rate X-rays and trigger a FLASH effect, which provides a basis for future scientific research and clinical application of HEX in FLASH radiotherapy.

Radioimmunotherapy Combined With Low-Intensity Ultrasound and Microbubbles: A Potential Novel Strategy for Treatment of Solid Tumors.

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.

Impact of Coronavirus Disease 2019 on Clinical Characteristics in Patients With Lung Cancer: A Large Single-Centre Retrospective Study.

Lung cancer is the most common cancer malignancy worldwide. With the continuous spread of the coronavirus disease 2019 (COVID-19) globally, it is of great significance to explore the impact of this disease on the clinical characteristics of lung cancer. Thus, we aimed to investigate whether the COVID-19 pandemic had any influence on the clinical characteristics and diagnosis of patients with lung cancer. We collected clinical and demographic data of patients who were newly diagnosed with lung cancer at our hospital between February 2019 and July 2020. Overall, 387 patients with lung cancer were divided into two groups for analysis: epidemic group (from February to July 2020) and pre-epidemic group (from February to July 2019). The source of diagnosis and clinical characteristics of the two groups were analysed. T-test and Mann-Whitney U were used for continuous variables, and Chi-squared or Fisher's exact test for categorical variable. We found that during the epidemic period, 110 cases of lung cancer were incidentally diagnosed during COVID-19 screening, accounting for 47.6% of all newly diagnosed lung cancer cases at our hospital. The proportions of patients who were diagnosed based on symptoms and physical examination in the epidemic group were 34.2 and 18.2%, respectively, while that in the pre-epidemic group were 41.7 and 58.3%, respectively. There was significant difference in the source of diagnosis between the two groups. In a subgroup analysis of the epidemic group, the average tumour volume of the patients diagnosed with COVID-19 screening was significantly smaller than that of the patients diagnosed with symptoms and physical examination. In conclusion, the continuation of the COVID-19 pandemic may impact the screening and clinical characteristics of lung cancer and require large-scale and longer-term observation.

FLASH Radiotherapy: History and Future.

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.

Radical radiotherapy for metachronous oligometastasis after initial treatment of esophageal cancer.

BACKGROUND AND PURPOSE: This study aimed to evaluate the efficacy of radical radiotherapy and assess prognostic factors in metachronous oligometastatic esophageal cancer (MOEC) patients after initial treatment with curative-intent surgery and/or chemoradiotherapy. MATERIALS AND METHODS: MOEC Patients during 2009-2018 in Mianyang Central Hospital were retrospectively analyzed. Each patient had ≤5 oligometastatic lesions, and the primary lesions were controlled in this study. Patients were devided into radiotherapy (RT) and non-radiotherapy (NRT) groups. The study endpoints were overall survival (OS) and treatment toxicities. RESULTS: This study included 82 patients who underwent intensity-modulated radiotherapy for MOEC. Median OS were 14 (95% confidence interval [CI], 11.0-17.0) and 7 (95% CI, 4.5-9.5) months for the RT and NRT groups, respectively (P = 0.016). Median OS were 18 (95% CI, 13.6-22.4) and 10 (95% CI, 5.1-14.9) months for lung and bone metastases, respectively (P = 0.010). Median OS were 15 (95% CI, 12.4-17.6) and 10 (95% CI, 7.6-12.4) months for interval time from initial diagnosis to metastasis ≥12 and <12 months, respectively (P = 0.026). Median OS were 16 (95% CI, 12.2-19.8) and 10 (95% CI, 5.0-15.0) months for biological effective dose (BED10) ≥ 60 Gy and BED10 < 60 Gy, respectively (P = 0.033). Cox multivariate regression analysis showed that treatment modality (RT vs. NRT) was an independent prognostic factor for MOEC patients (hazard ratio: 1.8, 95% CI: 1.1-3.0; P = 0.022). No toxic side effects greater than grade 3 were observed in all patients. CONCLUSIONS: Radiotherapy is a feasible and positive treatment for MOEC patients after initial treatment, a radical radiation dose with BED10 ≥ 60 Gy has benefits in extending survival. Radical radiotherapy should thus be considered for MOEC patients.

Randomized, self-controlled, prospective assessment of the efficacy of mometasone furoate local application in reducing acute radiation dermatitis in patients with head and neck squamous cell carcinomas.

BACKGROUND: Acute radiation dermatitis (ARD) is a common adverse effect in patients undergoing radiotherapy. Mometasone furoate cream (MMF) was reported to significantly reduce ARD, especially in breast cancer. Clinically, ARD is more critical and more difficult to prevent in patients with head and neck squamous cell carcinoma (HNSCC) than in those with breast cancer, because a higher dose of radiotherapy is required in HNSCC cases. The aim of this study was to evaluate the effect of MMF local application on radiation dermatitis in patients with HNSCC. METHODS: HNSCC patients scheduled for bilateral radical radiotherapy to the neck with identical radiation doses were enrolled. One side of the neck skin (test groups) of the patients were randomized to apply a thin layer of MMF once a day from the date of first radiotherapy until either 2 weeks after end of radiotherapy or until the test side skin developed ARD lesions, while the other side of neck (control groups) didn't apply any medication. The severity of ARD was evaluated weekly by using the modified radiation therapy oncology group score, pain intensity, and itch stages. RESULTS: Forty-one patients (82 targets) were analyzed. There was a significant difference between the ARD scores on the test side and the control side. MMF reduced the stages of ARD when the radiotherapy dose was <6000 cGY (P = .01) but showed no improvement when the dose was ≥6000 cGY (P = .699). Compared to the control side, local application of MMF significantly reduced the itch and pain scores of the test side skin regardless of the radiotherapy dose and ARD stage (P < .001) during radiotherapy. CONCLUSIONS: This study showed that MMF inunction after high-dose radiotherapy (>50 Gy) can prevent ARD, especially when the radiation dose is <6000 cGY.

Safety and efficacy of pulsed low-dose rate radiotherapy for local recurrent esophageal squamous cell carcinoma after radiotherapy: Study protocol for a prospective multi-center phase II trial.

INTRODUCTION: Re-irradiation after radiotherapy is a common treatment for locally recurrent esophageal cancer. However, the side effects of re-irradiation are serious. The most serious adverse reactions of re-irradiation include esophageal perforation and hemorrhage caused by esophageal perforation. Studies have shown that pulsed low-dose rate radiotherapy (PLDR) induces a hypersensitivity effect on tumor tissue and a hyper-repair effect on normal tissue, which can simultaneously reduce damage on the normal tissue and increase the therapeutic effect on the tumor. The objective of this study is to explore whether PLDR can reduce rate of esophageal perforation and improve efficacy in patients with recurrent esophageal squamous cell carcinoma (ESCC) after radiotherapy. METHODS AND ANALYSIS: This study is a prospective, multi-center, open, single-arm clinical trial designed to enroll 27 patients with locally recurrent ESCC after radiotherapy with or without chemotherapy. Re-irradiation will be performed using intensity modulated radiation therapy in 50 Gy/25 fractions. The strategy of PLDR includes dividing 2 Gy into 10 fractions, and administering each irradiating dose of 20 cGy at an interval of 3 minutes before the next low-dose irradiation. The actual dose rate of administration each time will be 16.67 cGy /minute. The primary endpoint in this study is the rate of esophageal perforation. The secondary endpoints are the objective remission rate, the palliative effect on quality of life and pain, and the time of disease progression. The observation time is 2 years after the end of the study. TRIAL REGISTRATION: Clinical trial number: ChiCTR1900020609.

A new method of lower extremity immobilization in radiotherapy.

We developed a new method for immobilization of the fix lower extremities by using a thermoplastic mask, a carbon fiber base plate, a customized headrest, and an adjustable angle holder. The lower extremities of 11 patients with lower extremity tumors were immobilized by this method. CT simulation was performed for each patient. For all 11 patients, the device fit was suitable and comfortable and had good reproducibility, which was proven in daily radiotherapy.

Immunohistochemical detection of the Raf kinase inhibitor protein in nonneoplastic gastric tissue and gastric cancer tissue.

Expression of the Raf kinase inhibitor protein (RKIP), a metastasis suppressor, is high in normal tissues, low in primary cancers, and lowest or absent in metastatic cancers. Here, we studied the expression of RKIP in nonneoplastic gastric tissue and gastric cancer tissue by immunohistochemistry (IHC) and evaluated its role in the genesis and metastasis of gastric cancer. RKIP immunoreactivity was evaluated in 40 samples of nonneoplastic gastric tissues and 75 samples of gastric cancer tissues. Among the 40 samples of nonneoplastic gastric tissue, 35 (87.5%) were positive for RKIP expression and 5 (12.5%) were negative; in the 75 samples of primary gastric cancer tissue, 39 (52%) were positive for RKIP expression and 36 (48%) were negative. Among 26 samples of metastatic lymph node tissues, 5 (19.2%) were positive for RKIP expression and 21 (80.8%) were negative. RKIP expression level was highest in nonneoplastic gastric tissue, low in primary gastric cancer tissue, and lowest or undetectable in metastatic gastric cancer tissue. Our data suggest that RKIP may play a role in the genesis and metastasis of gastric cancer.