Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups(25.4 months vs.15.2 months vs.12.0 months).Among patients receiving SBRT on lung lesions and brain metastases,the mPFS in the concurrent group was longer than that of the SBRT→ICIs group(29.6 months vs.11.4 months,P=0.0003 and 12.1 months vs.8.9 months,P=0.2559).Among patients receiving SBRT with<8 Gy and 8–12 Gy per fraction,the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group(20.1 months vs.5.3 months,P=0.0033 and 24.0 months vs.13.4 months,P=0.1311).The disease control rates of the lung,bone,and brain groups were 90.7%,83.3%,and 70.1%,respectively.Conclusion The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients.This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens.Dose fractionation regimens of 8–12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.

Evaluation of the 7^(th) edition of the TNM classification in patients with resected esophageal squamous cell carcinoma

AIM:To evaluate the prognostic factors and tumor stages of the 7th edition TNM classification for esophageal cancer.METHODS:In total,1033 patients with esophageal squamous cell carcinoma(ESCC)who underwent surgical resection with or without(neo)adjuvant therapy between January 2003 and June 2012 at the Thoracic Surgery DepartmentⅡof the Beijing Cancer Hospital,Beijing,China were included in this study.The following eligibility criteria were applied:(1)squamous cell carcinoma of the esophagus or gastroesophageal junction identified by histopathological examination;(2)treatment with esophagectomy plus lymphadenectomy with curative intent;and(3)complete pathologic reports and follow-up data.Patients who underwent non-curative(R1)resection and patients who died in hospital were excluded.Patients who received(neo)adjuvant therapy were also included in thisanalysis.All patients were restaged using the 7th edition of the Union for International Cancer Control and the American Joint Committee on Cancer TNM staging systems.Univariate and multivariate analyses were performed to identify the prognostic factors for survival.Survival curves were plotted using the Kaplan-Meier method,and the log-rank test was used to evaluate differences between the subgroups.RESULTS:Of the 1033 patients,273 patients received(neo)adjuvant therapy,and 760 patients were treated with surgery alone.The median follow-up time was 51.6mo(range:5-112 mo)and the overall 5-year survival rate was 36.4%.Gender,"p T"and"p N"descriptors,(neo)adjuvant therapy,and the 7th edition TNM stage grouping were independent prognostic factors in the univariate and multivariate analyses.However,neither histologic grade nor cancer location were independent prognostic factors in the univariate and multivariate analyses.The 5-year stage-based survival rates were as follows:ⅠA,84.9%;ⅠB,70.9%;ⅡA,56.2%;ⅡB,43.3%;ⅢA,37.9%;ⅢB,23.3%;ⅢC,12.9%andⅣ,3.4%.There were significant differences between each adjacent staging classification.Moreover,there were significant differences between each adjacent p N and p M subgroup.According to the p T descriptor,there were significant differences between each adjacent subgroup except between p T3 and p T4(P=0.405).However,there was no significant difference between each adjacent histologic grade subgroup and between each adjacent cancer location subgroup.CONCLUSION:The 7th edition is considered to be valid for patients with resected ESCC.However,the histologic grade and cancer location were not prognostic factors for ESCC.

Model based on γ-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis

AIM: To determine the prognostic value of alkaline phosphatase(ALP) and γ-glutamyltransferase(GGT) for hepatocellular carcinoma(HCC).METHODS: We analyzed the outcome of 172 HCC patients who underwent liver resection. Receiver operating characteristic(ROC) curve analysis was performed to determine the cut-off value of ALP and GGT. Then, preoperative risk factors for survival were evaluated by multivariate analysis. Based on the significant factors, aprognostic score model was established.RESULTS: By ROC curve analysis, ALP > 120 U/L and GGT > 115 U/L were considered elevated. Overall survival(OS) and tumor-free survival(TFS) for patients with elevated ALP and GGT were significantly worse than for patients with ALP and GGT within the normal range. Multivariate analysis showed that the elevated levels of ALP, GGT and tumor size were independent prognostic factors. Giving each positive factor as a score of 1, we established a preoperative prognostic score model. The 5-year OS for patients with a score of 0, 1, 2 and 3 were 84.0%, 45.9%, 44.1% and 0%, respectively, while the TFS was 80.6%, 40.0%, 38.8% and 0%, respectively. When combining patients with scores of 1 and 2 into the middle risk group, and patients with scores of 0 and 3 into the low-risk and highrisk groups, respectively, different outcomes would be significantly distinguished by the risk groups.CONCLUSION: Elevated ALP and GGT levels were risk predictors in HCC patients. Our prognostic model might vary the outcomes of patients from different risk groups.

A Centralized Report on Pediatric Japanese Encephalitis Cases from Beijing Children's Hospital,2013

Fifteen pediatric cases of suspected Japanese encephalitis （JE） were reported in Beijing Children＇s Hospital during the late summer of 2013. The clinical manifestations in most cases included high fever, seizures, and abnormal magnetic resonance imaging findings. Twelve of 15 cases were laboratory-confirmed as JE cases by pathogen identification. Epidemiological investigations showed that five of the 12 laboratory-confirmed patients had an incomplete JE vaccination history. Follow-up investigations after discharge indicated that seven laboratory-confirmed JE patients without JE vaccinations had relatively poor prognoses, with an average Modified Rankin Scale （MRS） score of 2.6 when compared with the other five laboratory-confirmed, JE-vaccinated patients with an average MRS score of 0.5. The observation of pediatric JE cases among those with a history of JE vaccination warrants further attention.

Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?

Sorafenib is the current standard treatment for advanced hepatocellular carcinoma(HCC),but its efficacy is modest with low response rates and short response duration. Predictive biomarkers for sorafenib efficacy are necessary. However,efforts to determine biomarkers for sorafenib have led only to potential candidates rather than clinically useful predictors. Studies based on patient cohorts identified the potential of blood levels of angiopoietin-2,hepatocyte growth factor,insulin-like growth factor-1,and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response,dynamic contrast-enhanced magnetic resonance imaging,and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new directions in biomarker research. These studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await validation. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced HCC.

Classifying extrahepatic bile duct metachronous carcinoma by de novo neoplasia site

Extrahepatic bile duct(EHBD)cancer may occur metachronously,and these cancers are resectable with a favorable prognosis.We aimed to identify the pattern of metachronous EHBD cancer.We classified the cases of metachronous EHBD cancer reported in the literature thus far and investigated two new cases of metachronous EHBD cancer.A 70-year-old female underwent R0 bile duct resection for a type 1 Klatskin tumor(pT-1N0M0).A 70-year-old male patient underwent R0 bile duct resection for a middle bile duct cancer(pT2N1M0).Imaging studies of both patients taken at 14 and 24mo after first surgery respectively revealed a metachronous cholangiocarcinoma that required pancreaticoduodenectomy(PD).Histopathology of the both tumors after PD revealed cholangiocarcinoma invading the pancreas(pT3N0M0).Both patients have been free from recurrence for 6 years and 16 mo respectively after the second surgery.Through a review of the literature on these cases,we classified the pattern of metachronous EHBD cancer according to the site of de novo neoplasia.The proximal remnant bile duct was most commonly involved.Metachronous EHBD cancer should be distinguished from an unresectable recurrent tumor.Classifying metachronous EHBD cancer may be helpful in identifying rare metachronous tumors.

Dynamic Regularity and Prognoses of Landslide

Dynamic regularity is discussed tightly combining with method and principle of displacement monitoring for landslide . By the principle of dynamic energy analysis is performed emphatically for the broken - line condi on of sliding surface being always made of multiple combination of unit geostructural planes with different dip angles .Several formulae are derived from given conditions and , presented to describe the dynamic regularity . Based on the regularity an example of huge landslide is cited to calculate water urge height of reservoir . By Poisson cycle principle the latter was made for another large slide . The results showed themselves to have very approached vis-a-vis the actual ones .

Metastatic Prostate Cancer under Androgen Deprivation Therapy: Factors Influencing Castration Resistance

Objective: To evaluate the factors predicting the time to progression to castration-resistant in metastatic prostate cancer under Androgen Deprivation Therapy (ADT) in our center. Patients and Methods: This is a retrospective, descriptive, analytical study in a single center over a period of 2 years. It has interest patients followed for metastasized prostate cancer under ADT. The parameters studied were: epidemiological, clinical, paraclinical, prostate specific antigen (PSA) nadir, time to nadir (TTN) and their link with the castration resistance. Results: The frequency of castration resistant prostate cancer was 28 patients per year. The mean age was 70.4 ± 7.9 years. An ECOG score ≥ 3 was more common as was the cT2c stage. The median of the initial total PSA was 489.6 ng/ml (203.3;1653.2). All patients had adenocarcinoma. The International Society of Urological Pathology (ISUP) 1 was more frequent. Bone metastases were more frequent. The medians of nadir, TTN and the castration resistance were 19.3 ng/ml (3.7;102.1), 5.5 months (3;9) and 11 months (6;15.3), respectively. The Eastern Cooperative Oncology Group (ECOG) score, clinical stage, metastatic site, the nadir and its TTN influenced the DSR. Age, lymph node involvement, initial total PSA and Gleason score did not influence the castration resistance. Conclusion: ADT should be initiated as soon as possible before an attack of general and/or clinical stage advanced to delay resistance. A drilling should be associated with this hormone therapy as much as possible because of its gain on resistance.

Predictive value of hypothermic machine perfusion parameters combined perfusate biomarkers in deceased donor kidney transplantation

Background:Delayed graft function(DGF)is the main cause of renal function failure after kidney transplantation.This study aims at investigating the value of hypothermic machine perfusion(HMP)parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor(DD)kidney transplantation.Methods:HMP parameters,perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1,2019 to August 31,2019 in the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis.Results:In this study,the DGF incidence was 17.7%(20/113);The multivariate logistic regression results showed that terminal resistance(OR:1.879,95%CI 1.145-3.56)and glutathione S-transferase(GST)(OR=1.62,95%CI 1.23-2.46)were risk factors for DGF;The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time(HR=0.823,95%CI 0.735-0.981).The model combining terminal resistance and GST(AUC=0.888,95%CI:0.842-0.933)significantly improved the DGF predictability compared with the use of terminal resistance(AUC=0.756,95%CI 0.693-0.818)or GST alone(AUC=0.729,95%CI 0.591-0.806).Conclusion:According to the factors analyzed in this study,the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.

A simple and successful treatment for rupture and defect of the posterior third superior sagittal sinus caused by open depressed skull fracture:A case report

It is extremely dangerous to treat the posterior third of the superior sagittal sinus (PTSSS) surgically, since it is usually not completely ligated. In this report, the authors described the case of a 27-year-old man with a ruptured and defective PTSSS caused by an open depressed skull fracture, which was treated by ligation of the PTSSS and the patient achieved a positive recovery. The patient's occiput was hit by a height-limiting rod and was in a mild coma. A CT scan showed an open depressed skull fracture overlying the PTSSS and a diffuse brain swelling. He underwent emergency surgery. When the skull fragments were removed, a 4 cm segment of the superior sagittal sinus (SSS) and the adjacent dura mater were removed together with bone fragments. Haemorrhage occurred and blood pressure dropped. We completed the operation by ligating the severed ends of the fractured sagittal sinus. One month after the operation, apart from visual field defects, he recovered well. In our opinion, in primary hospitals, when patients with severely injured PTSSS cannot sustain a long-time and complicated operation, e.g., the bypass using venous graft, and face life-threatening conditions, ligation of the PTSSS is another option, which may unexpectedly achieve good results.