Prevention of thromboembolic events after radical prostatectomy in patients with hereditary thrombophilia due to a factor V Leiden mutation by multidisciplinary coagulation management

Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia.The increased risk of thromboembolic events is three-to seven-fold in heterozygous and to 80-fold in homozygous patients.Methods:Within our prospectively collected database,we analysed 33006 prostate cancer patients treated with RP between December 2001 and December 2020.Of those,patients with factor V Leiden mutation were identified.All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation.Thromboembolic complications(deep vein thrombosis and pulmonary embolism)were assessed during hospital stay,as well as according to patient reported outcomes within the first 3 months after RP.Results:Overall,85(0.3%)patients with known factor V Leiden mutation were identified.Median age was 65(interquartile range:61-68)years.There was at least one thrombosis in 53(62.4%)patients and 31(36.5%)patients had at least one embolic event in their medical history before RP.Within all 85 patients with factor V Leiden mutation,we experienced no thromboembolic complications within the first 3 months after surgery.Conclusion:In our cohort of patients with factor V Leiden mutation,no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept.This may reassure patients with this hereditary condition who are counselled for RP.

Epidermal growth factor receptor mutation analysis in cytological specimens and responsiveness to gefitinib in advanced non-small cell lung cancer patients

Background： Epidermal growth factor receptor（EGFR） mutation is the key predictor of EGFR tyrosine kinase inhibitors（TKIs） efficacy in non-small cell lung cancer（NSCLC）. We conducted this study to verify the feasibility of EGFR mutation analysis in cytological specimens and investigate the responsiveness to gefitinib treatment in patients carrying EGFR mutations.Methods： A total of 210 cytological specimens were collected for EGFR mutation detection by both direct sequencing and amplification refractory mutation system（ARMS）. We analyzed EGFR mutation status by both methods and evaluated the responsiveness to gefitinib treatment in patients harboring EGFR mutations by overall response rate（ORR）, disease control rate（DCR） and progression free survival（PFS）.Results： Of all patients, EGFR mutation rate was 28.6%（60/210） by direct sequencing and 45.2%（95/210） by ARMS（P〈0.001） respectively. Among the EGFR wild type patients tested by direct sequencing, 26.7% of them were positive by ARMS. For the 72 EGFR mutation positive patients treated with gefitinib, the ORR, DCR and median PFS were 69.4%, 90.2% and 9.3 months respectively. The patients whose EGFR mutation status was negative by direct sequencing but positive by ARMS had lower ORR（48.0% vs. 80.9%, P=0.004） and shorter median PFS（7.4 vs. 10.5 months, P=0.009） as compared with that of EGFR mutation positive patients by both detection methods. Conclusions： Our study verified the feasibility of EGFR analysis in cytological specimens in advanced NSCLC. ARMS is more sensitive than direct sequencing in EGFR mutation detection. EGFR Mutation status tested on cytological samples is applicable for predicting the response to gefitinib. Abundance of EGFR mutations might have an influence on TKIs efficacy.

Two mutations in the transforming growth factor beta-induced gene associated with familial Lattice corneal dystrophy

AIM：To report a phenotypic variant pedigree of lattice corneal dystrophy（LCD）associated with two mutations,R124C and A546 D,in the transforming growth factor betainduced gene（TGFBI）.METHODS：A detailed ocular examination was taken for all participants of a LCD family. Peripheral blood leukocytes from each participant were extracted to obtain the DNA. Polymerase chain reaction（PCR）of all seventeen exons of TGFBI gene was performed. The products were sequenced and analyzed. Histological examination was carried out after a penetrating keratoplasty from the right eye of proband. RESULTS：Genetic analysis showed that the proband and all 6 affected individuals harbored both a heterozygous CGC to TGC mutation at codon 124 and a heterozygous GCC to GAC mutation at codon 546 of TGFBI. None of the 100 control subjects and unaffected family members was positive for these two mutations. Ocular examination displayed multiple refractile lattice-like opacities in anterior stroma of the central cornea and small granular deposits in the peripheral cornea. The deposits were stained positively with Congo red indicating be amyloid in nature and situated mainly in the anterior and middle stroma. CONCLUSION：We observed a novel LCD family which carried two pathogenic mutations（R124C and A546D）in the TGFBI gene. The phenotypic features were apparently different from those associated with corresponding single mutations. The result reveals that although the definite mutation is the most important genetic cause of the disease,some different modifier alleles may influence the phenotype.

Coexistence of anaplastic lymphoma kinase rearrangement in lung adenocarcinoma harbouring epidermal growth factor receptor mutation:A single-center study

BACKGROUND Accumulating evidences confirm that epidermal growth factor receptor(EGFR)mutation and anaplastic lymphoma kinase(ALK)rearrangement have coexisted in lung adenocarcinoma(LUAD).However,Its biological mechanism,clinicopathological features,and optimization of targeted drugs have not yet been completely elucidated.AIM To explore the clinical profile of LUAD patients with co-mutations of EGFR and ALK genes,with hopes of scientifically guiding similar patients towards selected,targeted drugs.METHODS Two hundred and thirty-seven LUAD patients were enrolled.EGFR mutations were detected by the amplification refractory mutation system-peptide nucleic acid technique,while the expression of ALK rearrangement was screened by the 5′/3′imbalance strategy for reverse transcription followed by quantitative polymerase chain reaction analysis.The clinicopathological features of these patients were analysed retrospectively,and the follow-up data were collected.RESULTS There were six cases with co-mutations of EGFR and ALK genes,which were more common in women,non-smoking and stage IV LUAD patients with bone metastasis,hence a positive rate of 2.53%(6/237).EGFR-tyrosine kinase inhibitors(EGFR-TKIs)were their preferred drugs for targeted therapy in these patients,with progression-free survival ranging from two months to six months.CONCLUSION In Gannan region,the positive rate of co-mutations of EGFR and ALK genes in LUAD patients is relatively high,and the co-mutations are more common in women,non-smoking and stage IV patients with bone metastasis.These patients prefer EGFR-TKIs as their preferred targeted drugs,but the therapeutic effect is not good.EGFR/ALK dual-TKIs may be more effective targeted drugs,which needs further study.

Atypical hemolytic-uremic syndrome due to complement factor Ⅰ mutation

Atypical hemolytic-uremic syndrome(a HUS) is a rare disease of complement dysregulation leading to thrombotic microangiopathy(TMA). Renal involvement and progression to end-stage renal disease are common in untreated patients. We report a 52-year-old female patient who presented with severe acute kidney injury, microangiopathic hemolytic anemia, and thrombocytopenia. She was managed with steroid, plasma exchange, and dialysis. Kidney biopsy shows TMA and renal cortical necrosis. Genetic analysis reveals heterozygous complement factor Ⅰ(CFI) mutation. Eculizumab was initiated after 3 mo of presentation, continued for 9 mo, and stopped because of sustained hematologic remission, steady renal function, and cost issues. Despite this, the patient continued to be in hematologic remission and showed signs of renal recovery, and peritoneal dialysis was stopped 32 mo after initiation. We report a case of a HUS due to CFI mutation, which, to the best of our knowledge, has not been reported before in Saudi Arabia. Our case illustrates the challenges related to the diagnosis and management of this condition, in which a high index of suspicion and prompt treatment are usually necessary.

Sequential chemotherapy and icotinib as first-line treatment for advanced epidermal growth factor receptor-mutated non-small cell lung cancer

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

Efficacy of EGFR Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer Patients Harboring Different Types of EGFR Mutations:A Retrospective Analysis

With the development of molecular pathology, many types of epidermal growth factor receptor（EGFR） mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors（EGFR-TKIs） in non-small cell lung cancer（NSCLC） patients with different types of EGFR mutations, especially in patients with single rare mutations or complex mutations（co-occurrence of two or more different mutations）, has not been fully understood. This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations. Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital, Wuhan, were retrospectively reviewed. The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed. Among these patients, 377 patients had only the EGFR del-19 mutation, 362 patients the EGFR L858R mutation in exon 21, 33 patients single rare mutations and 37 patients complex mutations. Among these 809 patients, 239 patients were treated with EGFR-TKIs. In all the 239 patients, the disease control rate（DCR） was 93.7% with two patients（0.2%） achieving complete response（CR）, the median progression free survival（PFS） was 13.0 months（95% confidence interval [CI], 11.6–14.4 months）, and the median overall survival（OS） was 55.0 months（95% CI, 26.3–83.7 months）. Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858 R mutation（P〈0.001）. Patients with classic mutations（del-19 and/or L858 R mutations） demonstrated longer PFS（P〈0.001） and OS（P=0.017） than those with uncommon mutations（single rare and/or complex mutations）. Furthermore, the patients with single rare mutations had shorter median OS than in those with other mutations. Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS（hazard ratio [HR]=0.308, 95% CI, 0.191–0.494, P〈0.001） and OS（HR=0.221, 95% CI, 0.101–0.480, P〈0.001）. The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations. The prognosis of the single rare EGFR mutations is depressing. EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR. Further studies in these patients with uncommon mutations（especially for the patients with single rare mutations） are needed to determine a better precision treatment.

Efficacy of third-line pemetrexed monotherapy versus pemetrexed combination with bevacizumab in patients with advanced EGFR mutation-positive lung adenocarcinoma

Objective： The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor（EGFR） mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.Patients and methods： One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin（GP） chemotherapy and second-line EGFR tyrosine kinase inhibitor（TKI） or with first-line EGFR-TKI and second-line GP chemotherapy.Results： The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups（P=0.04）. Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups（P=0.001）. Among 61 cases with thirdline pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different（P=0.001）.Conclusions： Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.

Dramatic response to immunotherapy in an epidermal growth factor receptor-mutant non-small cell lung cancer: A case report

BACKGROUND The advent of immune checkpoint inhibitors(ICIs)has revolutionized the management of several types of solid cancers,including lung cancer,by boosting the body's natural tumor killing response.However,it is undeniable that only a small proportion of non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations can achieve long-term responses and benefit from immunotherapy.CASE SUMMARY Herein,we report the case of a 48-year-old man diagnosed with stage IV lung adenocarcinoma with an EGFR L858R mutation who was administered pembrolizumab monotherapy followed by pemetrexed and achieved a 10-month progression-free survival interval.In this case report,we show that ICIs were effective for our patient with EGFR-mutated NSCLC and discuss the characteristics of patients who can benefit from immunotherapy.CONCLUSION We suggest that patients with EGFR-mutated NSCLC with high PD-L1 expression(defined as≥25%),the L858R mutation,smoking history,or pemetrexed pretreatment may benefit from immunotherapy.

Unexpected discovery of 2 cases of hepatocyte nuclear factor 1α-mutated infracentimetic adenomatosis

We present 2 cases of hepatocyte nuclear factor 1α (HNF1α)-mutated adenomatosis, discovered for reasons unrelated to this disease, and identified using immunohistochemical methods. These new tools may further our understanding of the link between adenomas/adenomatosis subtypes and their complications, and their association with other abnormalities.

Sequential occurrence of T790M mutation and small cell lung cancer transformation in EGFR-positive lung adenocarcinoma:A case report

BACKGROUND The emergence of secondary drug resistance when treating epidermal growth factor receptor(EGFR)mutated non-small cell lung cancer(NSCLC)using EGFRtyrosine kinase inhibitors(EGFR-TKIs),seriously affects the therapeutic efficacy and survival of patients.Here,we report a case of advanced NSCLC focusing on the application of multiple biopsy modalities to reveal the development of multiple resistance mechanisms during targeted therapies.CASE SUMMARY A 54-year-old male patient presented with EGFR 19Del-mutated advanced lung adenocarcinoma,and exhibited the development of a T790M mutation during initial TKI treatment.Following 3 mo of Osimertinib treatment,a mixed response was observed.Tissue biopsy of the progressive lesion showed transformation to small cell lung cancer(SCLC)harboring RB1 and TP53 mutations,with loss of the original T790M mutation.A standard chemotherapy regimen with Anlotinib for SCLC was administered.Repeat biopsy revealed adenocarcinoma combined with SCLC after tumor progression.The patient’s overall survival was 24 mo.CONCLUSION Multiple biopsy modalities can reveal the development of multiple resistance mechanisms which help with treatment decision-making.Comprehensive treatment regimens according to the drug resistance mechanism significantly improved the prognosis of such patients.

Gefitinib combined with γ-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen

Objective： The senile lung adenocarcinoma patients harboring an activating epidermal growth factor receptor （EGFR） mutation shows good and rapid response to EGFR tyrosine kinase inhibitors （TKIs）. Whether gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen is still under investigation. Methods： The 42 senile lung adenocarcinoma patients with EGFR mutations were divided into 2 groups according to the therapy method. Group A was the 22 patients treated with gefitinib combined with y-ray stereotactic body radiation therapy （SBRT）. Group B was the 20 patients treated with gefitinib alone. All of the patients received gefitinib of 250 mg/d from the first day until disease progression or other reasons. The patients of Group A were treated with y-ray stereotactic body radiation therapy from the second day. Radiation fields included the primary lesions and the integration of lymph nodes. Dose curve of this group was 50%-80%. Encircled dose was 4.0-6.5 Gy per fraction and the range of total dose was 40-52 Gy. We treated the patients 8-12 times and treated five times every week. Results： All the patients were examined by enhanced double helix CT at the second month. The tumor response rate （RR） of group A was 81.8% （18/22）. Disease control rate （DCR） was 90.9% （20/22）. The median overall survival （OS） was 24.2 months （range 8-58 months ） and the progression-free survival （PFS） was 18.6 months. The overall 1-year survival rate was 72.3% （16/22） and 2-year survival rate was 54.5% （12/22）. The main side effects included skin rash and diarrhea. The RR of group B was 50.0 % （10/20）. DCR was 75.0% （15/20）. OS was 17.4 months （range 6-32 months ） and PFS was 12.1 months. The overall 1-year survival rate was 60.0% （12/20） and 2-year survival rate was 40.0% （8/20）. The main side effects included skin rash and diarrhea. The group A who were treated with gefitinib combined with y-ray stereotactic body radiation therapy had a higher short term therapeutic effects （RR） and long term therapeutic effects （OS） than group B who were treated with gefitinib alone respectively （81.8% vs 50.0%, P = 0.029 〈 0.05, x2 = 4.773 and 24.2 vs 17.4, P = 0.024 〈 0.05, X2 = 5.098）. Conclu. sion： Gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen. The side affects are acceptable.

Seepage safety monitoring model for an earth rock dam under influence of high-impact typhoons based on particle swarm optimization algorithm

Extreme hydrological events induced by typhoons in reservoir areas have presented severe challenges to the safe operation of hydraulic structures. Based on analysis of the seepage characteristics of an earth rock dam, a novel seepage safety monitoring model was constructed in this study. The nonlinear influence processes of the antecedent reservoir water level and rainfall were assumed to follow normal distributions. The particle swarm optimization （PSO） algorithm was used to optimize the model parameters so as to raise the fitting accuracy. In addition, a mutation factor was introduced to simulate the sudden increase in the piezometric level induced by short-duration heavy rainfall and the possible historical extreme reservoir water level during a typhoon. In order to verify the efficacy of this model, the earth rock dam of the Siminghu Reservoir was used as an example. The piezometric level at the SW1-2 measuring point during Typhoon Fitow in 2013 was fitted with the present model, and a corresponding theoretical expression was established. Comparison of fitting results of the piezometric level obtained from the present statistical model and traditional statistical model with monitored values during the typhoon shows that the present model has a higher fitting accuracy and can simulate the uprush feature of the seepage pressure during the typhoon perfectly.

An improved adaptive differential evolution algorithm for single unmanned aerial vehicle multitasking

Single unmanned aerial vehicle(UAV)multitasking plays an important role in multiple UAVs cooperative control,which is as well as the most complicated and hardest part.This paper establishes a threedimensional topographical map,and an improved adaptive differential evolution(IADE)algorithm is proposed for single UAV multitasking.As an optimized problem,the efficiency of using standard differential evolution to obtain the global optimal solution is very low to avoid this problem.Therefore,the algorithm adopts the mutation factor and crossover factor into dynamic adaptive functions,which makes the crossover factor and variation factor can be adjusted with the number of population iteration and individual fitness value,letting the algorithm exploration and development more reasonable.The experimental results implicate that the IADE algorithm has better performance,higher convergence and efficiency to solve the multitasking problem compared with other algorithms.

Novel Mutation of Cleidocranial Dysplasia-related Frameshift Runt-related Transcription Factor 2 in a Sporadic Chinese Case

Background： Cleidocranial dysplasia （CCD） is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of the fontanels, midface hypoplasia, short stature, and delayed eruption of permanent and supernumerary teeth. Previous studies reported a connection between CCD and the haploinsufficiency of runt-related transcription factor 2 （RUNX2）. Here, we report a sporadic Chinese case presenting typical symptoms of CCD. Methods： We made genetic testing on this sporadic Chinese case and identified a novel RUNX2 ffameshift mutation： c.1111 dupT. In situ immunofluorescence microscopy and osteocalcin promoter luciferase assay were performed to compare the functions of the RUNX2 mutation with those of wild-type RUNX2. Results： RUNX2 mutation was observed in the perinuclear region, cytoplasm, and nuclei. In contrast, wild-type RUNX2 was confined in the nuclei, which indicated that the subcellular compartmentalization of RUNX2 mutation was partially perturbed. The transactivation function on osteocalcin promoter of the RUNX2 mutation was obviously abrogated. Conclusions： We identified a sporadic CCD patient carrying a novel insertion/frameshift mutation of RUNX2. This finding expanded our understanding of CCD-related phenotypes.

Epidemiological aspects of Budd-Chiari in Egyptian patients:A single-center study

AIM： TO describe the socio-demographic features, etiology, and risk factors for Budd-Chiari syndrome （BCS） in Egyptian patients. METHODS： Ninety-four Egyptian patients with confirmed primary Budd-Chiari syndrome were presented to the Budd-Chiari Study Group （BCSG） and admitted to the Tropical Medicine Department of Ain Shams University Hospital （Cairo, Egypt）. Complete clinical evaluation and laboratory investigations, including a thrombophilia workup and full radiological assessment, were performed to determine underlying disease etiologies.RESULTS： BCS was chronic in 79.8% of patients, acute or subacute in 19.1%, and fulminant in 1.1%. Factor V Leiden mutation （FVLM） was the most common etiological cause of disease （53.1%）, followed by mutation of the gene encoding methylene tetrahydrofolate reductase （MTHFR） （51.6%）. Current or recent hormonal treatment was documented in 15.5% of females, and BCS associated with pregnancy was present in 17.2% of females. Etiology could not be determined in 8.5% of patients. Males had significantly higher rates of MTHFR gene mutation and Behcet＇ s disease, and females had significantly higher rates of secondary antiphospholipid antibody syndrome. A highly significant positive relationship was evident between the presence of Behcet＇s disease and inferior vena caval occlusion, either alone or combined with occlusion of the hepatic veins （,0 〈 0.0001）. CONCLUSION： FVLM is the most common disease etiology and MTHFR the second most common in Egyptian BCS patients. BCS etiology tends to vary with geographic region.

Early detection of circulating tumor DNA and successful treatment with osimertinib in thr790met-positive leptomeningeal metastatic lung cancer:A case report

BACKGROUND Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal(LM)metastasis than other types of lung cancers and have a poor prognosis.Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis.CASE SUMMARY A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital.She was diagnosed with lung adenocarcinoma with osseous metastasis 10 months prior to admittance.epidermal growth factor receptor(EGFR)mutation was detected by genomic examination,so she was first treated with gefitinib for 10 months before acquiring resistance.Cell-free cerebrospinal fluid(CSF)circulating tumor DNA detection by next-generation sequencing was conducted and indicated the EGFR-Thr790Met mutation,while biopsy and cytology from the patient’s CSF and the first enhanced cranial magnetic resonance imaging(MRI)showed no positive findings.A month later,the enhanced MRI showed linear leptomeningeal enhancement,and the cytology and biochemical examination in CSF remained negative.Therefore,osimertinib(80 mg/d)was initiated as a second-line treatment,resulting in a good response within a month.CONCLUSION This report suggests clinical benefit of osimertinib in LM patients with positive detection of the EGFR-Thr790Met mutation in CSF and proposes that the positive findings of CSF circulating tumor DNA as a liquid biopsy technology based on the detection of cancer-associated gene mutations may appear earlier than the imaging and CSF findings and may thus be helpful for therapy.Moreover,the routine screening of chest CT with the novel coronavirus may provide unexpected benefits。

Stereotactic body radiation therapy:A good dance partner of oligometastatic non-small cell lung cancer to the sound of SINDAS study

The European Organization for Research on Treatment of Cancer Research published a consensus statement to establish the key criteria to define oligometastatic disease(OMD).According to those criteria,all lesions(both primary and metastatic)should be amenable to radical intent treatment with acceptable toxicity.Several retrospective studies have shown that adding local ablative therapy to the treatment of OMD improves outcomes;however,due to the diverse selection criteria and treatment strategies used in those studies,it is difficult to compare directly results to draw definitive conclusions.In recent years,prospective phase II trials,such as the SABR-COMET and"Oligomez"trials,have shown that stereotactic body radiation therapy(SBRT)improves outcomes in patients with OMD.More recently,interim results of the randomised phase 3 SINDAS trial were reported at the annual meeting of the American Society of Clinical Oncology 2020 demonstrating that upfront SBRT added to systemic treatment with tyrosine kinase inhibitors yielded a significant benefit in both progression-free survival and overall survival in patients with epidermal growth factor receptor-mutant oligometastatic non-small cell lung cancer.In the present editorial,we review the definition and historical context of advanced non-small cell lung cancer with OMD.In addition,we review the scientific evidence for local ablative therapy and SBRT and discuss the results of recently published prospective studies.We also discuss in depth the results of the SINDAS study,including the strengths and weaknesses of the study and the barriers to extrapolating these results to routine clinical practice.

Histological transformation of non-small cell lung cancer:Clinical analysis of nine cases

BACKGROUND Histological transformation is one of the numerous mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors(EGFRTKIs).Given its rarity,the underlying transformational mechanisms,clinical features,and therapeutic prognoses are only studied through limited case reports.AIM To analyze the clinical characteristics and underlying mechanisms in non-small cell lung cancer(SCLC)patients with histological transformation after treatment with EGFR-TKIs.METHODS We retrospectively investigated nine patients diagnosed with non-SCLC transforming to SCLC,large-cell neuroendocrine carcinoma(LCNEC),or squamous cell carcinoma on re-biopsy after first-or third-generation EGFR-TKIs.RESULTS The median age of nine patients was 60 years.Among them,six patients had the EGFR 19del mutation,one had the L858R mutation,and one had wild-type EGFR.The level of plasma NSE was measured in six patients with SCLC or LCNEC transformation when transformation occurred,and five patients had elevated plasma NSE levels.All patients received standard chemotherapy after transformation with the exception of one patient who received chemotherapy and anlotinib.CONCLUSION Tumor re-biopsy should be performed routinely when EGFR-TKI therapy fails in lung cancer patients to avoid ignoring histological transformation and to select a subsequent therapeutic strategy.The transformed tumor retained the original EGFR mutation,indicating that histological transformation represents an evolution from the initial tumor.

Like father, like son: Pulmonary thromboembolism due to inflammatory or hereditary condition? Two case reports

BACKGROUND Venous thromboembolism,which includes deep venous thrombosis and pulmonary embolism,is a well-known causal disorder with high morbidity and mortality rates.Inherited or acquired conditions affecting components of coagulation and fibrinolysis systems have been linked to venous thromboembolism pathogenesis as they may lead to a pro-inflammatory state in human bodies.Toxoplasmosis is a zoonosis that potentially leads to acute systemic cachectic-inflammatory effects in experimental animal models but is not yet proven in humans.It is known that venous thrombosis can occur during acute inflammatory/infectious diseases,although it is not well established with regard to toxoplasmosis alone.CASE SUMMARY A 70-year-old Caucasian man and his 32-year-old son developed general malaise,chills,fever,and myalgia,having established a diagnosis of toxoplasmosis.Twenty days later,they presented dry cough leading to further investigations that revealed an incidental deep venous thrombosis plus pulmonary embolism in them both.Thrombophilia screening showed both patients had a factor V Leiden mutation heterozygosis.Father and son completely recovered without any sequalae after anticoagulant treatment.They have not presented symptom recurrence of either medical disorder during 1 year of follow-up.CONCLUSION Toxoplasmosis may enhance the risk of venous thromboembolism in patients showing factor V Leiden mutation heterozygosis.