RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

RARRES2's impact on lipid metabolism in triplenegative breast cancer:a pathway to brain metastasis

Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.

Radiotherapy for hyoid bone metastasis from lung adenocarcinoma:A case report

BACKGROUND Metastasis to the hyoid bone is an exceptionally rare occurrence,with documented cases limited to breast,liver,colon,skin,lung,and prostate cancers.This report highlights an unusual case involving the metastasis of lung adenocarcinoma to the hyoid bone,accompanied by a distinctive headache.Previous documentation involved surgical resection of the hyoid mass.We present a case displaying the benefits of palliative radiotherapy.CASE SUMMARY A 72-year-old non-smoking,non-alcoholic woman,initially under investigation for a year-long elevation in absolute lymphocyte count,presented with a monthlong history of intermittent throat pain.Despite negative findings in gastroenterological and otolaryngologic examinations,a contrast-enhanced chest computed tomography scan revealed a mediastinal mass and questionable soft tissue thickening in her left anterolateral neck.Subsequent imaging and biopsies confirmed the presence of lung adenocarcinoma metastasis to the hyoid bone.The patient was treated with platinum-based chemo-immunotherapy along with pembrolizumab.Ultimately,the lung cancer was unresponsive.Our patient opted for palliative radiation therapy instead of surgical resection to address her throat pain.As a result,her throat pain was alleviated,and it also incidentally resolved her chronic headaches.This is the second documented case of lung adenocarcinoma metastasizing to the hyoid bone.CONCLUSION Palliative radiotherapy may add to the quality of life in symptomatic patients with cancer metastatic to the hyoid bone.

Prognostic factors of breast cancer brain metastasis

In this editorial we comment on the article by Chen et al published in the recent issue of the World Journal of Clinical Oncology.Brain metastasis is one of the most serious complications of breast cancer and causes high morbidity and mortality.Brain metastases may involve the brain parenchyma and/or leptomeninges.Symptomatic brain metastases develop in 10%-16%of newly recognized cases each year,and this rate increases to 30%in autopsy series.Depending on the size of the metastatic foci,it may be accompanied by extensive vasogenic edema or may occur as small tumor foci.Since brain metastases are a significant cause of morbidity and mortality,early diagnosis can have significant effects on survival and quality of life.The risk of developing brain metastases emerges progressively due to various patient and tumor characteristics.Patient variability may be particularly important in the susceptibility and distribution of brain metastases because malignant blood must cross the brain barrier and move within the brain parenchyma.Some characteristics of the tumor,such as gene expression,may increase the risk of brain metastasis.Clinical growth,tumor stage,tumor grade,growth receptor positivity,HER2 positivity,molecular subtype(such as triple negative status,luminal/nonluminal feature)increase the risk of developing breast cancer metastasis.Factors related to survival due to breast cancer brain metastasis include both tumor/patient characteristics and treatment characteristics,such as patient age,lung metastasis,surgery for brain metastasis,and HER2 positivity.If cases with a high risk of developing brain metastasis can be identified with the help of clinical procedures and artificial intelligence,survival and quality of life can be increased with early diagnosis and treatment.At the same time,it is important to predict the formation of this group in order to develop new treatment methods in cases with low survival expectancy with brain metastases.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Navigating breast cancer brain metastasis:Risk factors,prognostic indicators,and treatment perspectives

In this editorial,we comment on the article by Chen et al.We specifically focus on the risk factors,prognostic factors,and management of brain metastasis(BM)in breast cancer(BC).BC is the second most common cancer to have BM after lung cancer.Independent risk factors for BM in BC are:HER-2 positive BC,triplenegative BC,and germline BRCA mutation.Other factors associated with BM are lung metastasis,age less than 40 years,and African and American ancestry.Even though risk factors associated with BM in BC are elucidated,there is a lack of data on predictive models for BM in BC.Few studies have been made to formulate predictive models or nomograms to address this issue,where age,grade of tumor,HER-2 receptor status,and number of metastatic sites(1 vs>1)were predictive of BM in metastatic BC.However,none have been used in clinical practice.National Comprehensive Cancer Network recommends screening of BM in advanced BC only when the patient is symptomatic or suspicious of central nervous system symptoms;routine screening for BM in BC is not recommended in the guidelines.BM decreases the quality of life and will have a significant psychological impact.Further studies are required for designing validated nomograms or predictive models for BM in BC;these models can be used in the future to develop treatment approaches to prevent BM,which improves the quality of life and overall survival.

Research Progress in Brain Metastasis of Breast Cancer

The incidence rate of breast cancer is very high.Some patients were diagnosed as stage IV patients at the first diagnosis and had distant metastasis.Bone,lung and liver are the common metastatic sites of breast cancer.Although brain is the least common metastatic site of breast cancer,the incidence of brain metastasis in newly diagnosed breast cancer patients is increasing year by year.After brain metastasis,the disease develops rapidly,and because of the existence of blood cerebrospinal fluid barrier,it is difficult for drugs to reach the focus,and the curative effect is poor,leading to poor prognosis of patients with brain metastasis of breast cancer.Previous studies have also explored the clinical characteristics of brain metastases from breast cancer and the factors affecting prognosis.Different ages,races,histological grades,T stages,N stages,molecular subtypes,and pathological types are the main factors affecting the occurrence and prognosis of brain metastases from breast cancer.Studies on the characteristics,mechanisms,and treatment plans of brain metastases from breast cancer have also been reported at home and abroad.This article reviews the clinical characteristics,pathogenesis and treatment progress of brain metastases from breast cancer,aiming to provide some ideas and basis for clinical diagnosis and treatment and drug research of brain metastases from breast cancer.

Analysis of clinicopathological features and prognostic factors of breast cancer brain metastasis

BACKGROUND Breast cancer(BC)has become the most common malignancy in women.The incidence and detection rates of BC brain metastasis(BCBM)have increased with the progress of imaging,multidisciplinary treatment techniques and the extension of survival time of BC patients.BM seriously affects the quality of life and survival prognosis of BC patients.Therefore,clinical research on the clinicopathological features and prognostic factors of BCBM is valuable.By analyzing the clinicopathological parameters of BCBM patients,and assessing the risk factors and prognostic indicators,we can perform hierarchical diagnosis and treatment on the high-risk population of BCBM,and achieve clinical benefits of early diagnosis and treatment.AIM To explore the clinicopathological features and prognostic factors of BCBM,and provide references for diagnosis,treatment and management of BCBM.METHODS The clinicopathological data of 68 BCBM patients admitted to the Air Force Medical Center,Chinese People’s Liberation Army(formerly Air Force General Hospital)from 2000 to 2022 were collected.Another 136 BC patients without BM were matched at a ratio of 1:2 based on the age and site of onset for retrospective analysis.Categorical data were subjected to χ^(2) test or Fisher’s exact probability test,and the variables with P<0.05 in the univariate Cox proportional hazards model were incorporated into the multivariate model to identify high-risk factors and independent prognostic factors of BCBM,with a hazard ratio(HR)>1 suggesting poor prognostic factors.The survival time of patients was estimated by the Kaplan-Meier method,and overall survival was compared between groups by log-rank test.RESULTS Multivariate Cox regression analysis showed that patients with stage Ⅲ/Ⅳ tumor at initial diagnosis[HR:5.58,95% confidence interval(CI):1.99–15.68],lung metastasis(HR:24.18,95%CI:6.40-91.43),human epidermal growth factor receptor 2(HER2)-overexpressing BC and triple-negative BC were more prone to BM.As can be seen from the prognostic data,52 of the 68 BCBM patients had died by the end of follow-up,and the median time from diagnosis of BC to the occurrence of BM and from the occurrence of BM to death or last follow-up was 33.5 and 14 mo,respectively.It was confirmed by multivariate Cox regression analysis that patients with neurological symptoms(HR:1.923,95%CI:1.005-3.680),with bone metastasis(HR:2.011,95%CI:1.056-3.831),and BM of HER2-overexpressing and triple-negative BC had shorter survival time.CONCLUSION HER2-overexpressing,triple-negative BC,late tumor stage and lung metastasis are risk factors of BM.The presence of neurological symptoms,bone metastasis,and molecular type are influencing prognosis factors of BCBM.

Brain metastasis in non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations： a report of seven cases and literature review

Brain metastasis(BM)arising from non-small cell lung cancer(NSCLC)with rare epidermal growth factor receptor(EGFR)mutations is quite rare.The prognosis and therapeutic effects of BM remain enigmatic.To the best of our knowledge,this is the first report to make a separate analysis of BM from NSCLC patients with original uncommon EGFR mutations.We retrospectively reviewed 7 cases of BM arising from 42 cases of uncommon EGFR mutated lung cancer in Tianjin Medical University Cancer Institute and Hospital.We also performed a literature review to assess therapeutic features and outcomes.

Incidence and treatment of brain metastasis in patients with esophageal carcinoma

Brain metastasis from esophageal carcinoma(BMEC) is very rare, but its incidence has increased in the United States, Japan, China and other counties. Reports on BMEC have largely been focused on examining whether adjuvant therapy for esophageal cancer influences the survival duration of BMEC patients and on the imaging characteristics of BMEC determined using new medical equipment. The difference between different pathological types of esophageal cancer, especially adenocarcinoma and squamous cell carcinoma, is one important factor used to assess the influence of BMEC. Adjuvant therapy, including radiotherapy and chemotherapy, for esophageal cancer with different characteristics in different countries may affect BMEC treatment outcomes. The degree of popularization of advanced medical equipment is a major concern related to the prevalence of BMEC. Furthermore,targeted BMEC treatment is under development in developed countries. In this article, we reviewed the debate surrounding BMEC and analyzed BMEC studies from different perspectives.

Brain metastasis in children with stage 4 neuroblastoma after multidisciplinary treatment

Introduction: Brain metastasis is common in relapsed neuroblastoma patients, but the characteristics of brain metastasis remain largely unknown. This study aimed to investigate the status of brain metastasis with neuroblastoma in South China.Methods: In this retrospective case?based study, 106 patients with stage 4 neuroblastoma from the Department of Pediatric Oncology in Sun Yat?sen University Cancer Center between January 2004 and May 2013 were included. The incidence, risk factors, and survival status of these patients were reviewed and analyzed.Results: Of the 106 patients, 11(10.4%) developed brain metastasis, accounting for 20.0% of 55 patients with relapse or progression. The age at initial diagnosis of the 11 patients ranged from 2 to 10 years(median 4 years), which was younger than that of the patients without brain metastasis(median 5 years, range 1–10 years, P = 0.073). The male to female ratio of the 11 patients was 8:3, which was not signiicantly diferent from that of the patients with?out brain metastasis(P = 0.86). Patients with brain metastasis had higher lactate dehydrogenase levels than those without brain metastasis, but the diferences were not signiicant(P initial diagnosis to the develo= 0.076). Eight patients died, and 3 patients survived. The median interval from thepment of brain metastasis was 18 months(range 6–32 months). The median survival was 4 months(range 1 day to 29 months) after the diagnosis of brain metastasis. The median interval from the manifestation of brain metastasis to death was 3 months(range 1 day to 11 months).Conclusions: High?risk factors for brain metastasis in cases of neuroblastoma include bone marrow involvement and a younger age at initial diagnosis. Nevertheless, multiple treatment modalities can improve disease?free survival.

Relationship between HER-2 overexpression and brain metastasis in esophageal cancer patients

AIM:To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.METHODS:We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010.Data analyzed consisted of demographic and clinical variables.The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test.RESULTS:One hundred and forty two patients were reviewed.Median age was 64 years(36-86 years).Eighty eight patients(62%) received neoadjuvant chemoradiotherapy.Pathological complete and partial responses were achieved in 17(19%) and 71(81%) patients.Cancer relapsed in 43/142(30%) patients.The brain was the first site of relapse in 9/43 patients(21%,95% CI:10%-36%).HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9(56%) cases overexpressed HER-2(3+ staining).CONCLUSION:HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy.Further studies will be required to validate this observation.

Brain metastasis in advanced colorectal cancer： results from the South Australian metastatic colorectal cancer (SAmCRC) registry

Objective:Brain metastasis is considered rare in metastatic colorectal cancer(mCRC);thus,surveillance imaging does not routinely include the brain.The reported incidence of brain metastases ranges from 0.6% to 3.2%.Methods:The South Australian mCRC Registry(SAmCRC)was analyzed to assess the number of patients presenting with brain metastasis during their lifetime.Due to small numbers,a descriptive analysis is presented.Results:Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis(1.4%).The clinical characteristics of those with brain metastasis were as follows:the median age was 65.3 years and 51% were female.Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation status of the tumor was known,the majority harbored a KRAS mutation(55%);31(53%)underwent craniotomy and 55(93%)underwent whole-brain radiotherapy.The median survival time from diagnosis of brain metastasis was 4.2 months(95% confidence interval 2.9–5.5).Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy(8.5 months vs.2.2 months,respectively).Data from the SAmCRC(a population-based registry)confirm that brain metastases are rare and the median time to development is approximately 2 years.Conclusions:Brain metastasis is a rare outcome in advanced CRC.Patients within the registry tended to be female,young in age,and harbored with higher rates of KRAS mutations.Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately,most patients with central nervous system involvement die from their extracranial disease.

Recursive Partitioning Analysis Classification and Graded Prognostic Assessment for Non-Small Cell Lung Cancer Patients with Brain Metastasis:A Retrospective Cohort Study

Objective：To assess prognostic factors and validate the effectiveness of recursive partitioning analysis （RPA） classes and graded prognostic assessment （GPA） in 290 non-small cell lung cancer （NSCLC） patients with brain metastasis （BM）.Methods：From Jan 2008 to Dec 2009,the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation,systemic chemotherapy and tyrosine kinase inhibitors （TKIs） in two institutes were analyzed.Survival was estimated by Kaplan-Meier method.The differences of survival rates in subgroups were assayed using log-rank test.Multivariate Cox＇s regression method was used to analyze the impact of prognostic factors on survival.Two prognostic indexes models （RPA and GPA） were validated respectively.Results：All patients were followed up for 1-44 months,the median survival time after brain irradiation and its corresponding 95% confidence interval （95% CI） was 14 （12.3-15.8） months.1-,2-and 3-year survival rates in the whole group were 56.0%,28.3%,and 12.0%,respectively.The survival curves of subgroups,stratified by both RPA and GPA,were significantly different （P0.001）.In the multivariate analysis as RPA and GPA entered Cox＇s regression model,Karnofsky performance status （KPS） ≥ 70,adenocarcinoma subtype,longer administration of TKIs remained their prognostic significance,RPA classes and GPA also appeared in the prognostic model.Conclusion：KPS ≥70,adenocarcinoma subtype,longer treatment of molecular targeted drug,and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.

Prognostic factors affecting long-term outcomes in patients with brain metastasis from esophageal carcinoma

Objective: The incidence of brain metastasis from esophageal cancer(BMEC) has increased in recent years.Thus, it is necessary to identify factors that affect long-term outcomes for such patients.Methods: From January 1997 to July 2018, consecutive patients(10,043 patients, 31 with brain metastasis) with esophageal cancer(EC) treated at Zhejiang Cancer Hospital were recruited for retrospective analysis.Demographic, clinical, and pathological variables and the survival data were retrieved.Results: The median time from diagnosis of EC to diagnosis of brain metastases was 7.67(range, 0.43-55.20)months. The median survival time of BMEC patients from diagnosis of primary esophageal tumor was 16.7(range,2.33-163.30) months and the median survival time from the point of diagnosis of brain metastasis was 6.47(range,0.43-148.13) months. Univariate and multivariate analyses showed that the pathology type, EC without chemotherapy, and bone metastasis history were significantly associated with a shorter time interval between the first treatment of EC and brain metastasis. Chemotherapy history after brain metastasis, whole brain radiation therapy(WBRT) history, and surgery were significant predictors for better long-term survival outcomes.Conclusions: Our findings indicate that the use of surgery, WBRT, and chemotherapy can achieve the best therapeutic effects for BMEC patients.

Incidence of brain metastasis in patients with esophageal carcinoma

AIM:To determine the incidence of brain metastasis in a contemporary group of patients with carcinoma of the esophagus.METHODS:Retrospective analysis of 53 patients with esophageal carcinoma who received radiotherapy as a component of treatment between 1998 and 2007,including patient and tumor characteristics,and subsequent diagnosis of brain metastasis.The association between the histological type of esophageal cancer and the incidence of brain metastasis was assessed using Fisher's exact test.RESULTS:Forty-four of the fifty-three patients in this study had adenocarcinoma and nine had squamous cell carcinoma,ranging from stage ⅡA-ⅣB.Primary treatment was surgery with neoadjuvant chemoradiotherapy (trimodality therapy) in 19% of patients;chemoradiotherapy in 42%;and surgery and adjuvant radiotherapy in 7%.Twenty-five percent of patients inthis study received palliative radiotherapy.The overall incidence of brain metastasis in this cohort was 13%.Adenocarcinoma was the primary tumor histology in all of the patients who developed brain metastasis,representing an incidence of 16% in this subgroup.No patients with squamous cell carcinoma received trimodality therapy.The association between histology and brain metastasis was not statistically significant.CONCLUSION:The incidence of brain metastasis in this contemporary cohort of patients with esophageal carcinoma is higher than previously reported and was confined to those with adenocarcinoma.

Prognostic scoring system for synchronous brain metastasis at diagnosis of colorectal cancer: A population-based study

BACKGROUND Brain metastasis(BM)from colorectal cancer(CRC)is rarely encountered clinically,and its prognosis has not been fully evaluated.AIM To construct a scoring system and accurately predict the survival of patients with synchronous BM at diagnosis of CRC.METHODS A retrospective study of 371 patients with synchronous BM from CRC was performed,using the data from 2010 to 2014 from the Surveillance,Epidemiology,and End Results database.Survival time and prognostic factors were statistically analyzed by the Kaplan-Meier method and Cox proportional hazards models,respectively.A scoring system was developed using the independent prognostic factors,and was used to measure the survival difference among different patients.RESULTS For the 371 patients,the median overall survival was 5 mo,survival rates were 27%at 1 year and 11.2%at 2 years.Prognostic analysis showed that age,carcinoembryonic antigen level and extracranial metastasis to the liver,lung or bone were independent prognostic factors.A scoring system based on these three prognostic factors classified the patients into three prognostic subgroups(scores of 0-1,2-3,and 4).The median survival of patients with scores of 0-1,2-3 and 4 was 14,5 and 2 mo,respectively(P<0.001).Subgroup analysis showed that there were significant differences in prognosis among the groups.Score 2-3 vs 0-1:hazard ratio(HR)=2.050,95%CI:1.363-3.083;P=0.001;score 4 vs 0-1:HR=3.721,95%CI:2.225-6.225;P<0.001;score 2-3 vs 4:HR=0.551,95%CI:0.374-0.812;P=0.003.CONCLUSION The scoring system effectively distinguishes long-term and short-term survivors with synchronous BM from CRC.These results are helpful in providing a reference for guiding therapy.

Surgery Versus Stereotactic Radiosurgery for Single Synchronous Brain Metastasis from Non-Small Cell Lung Cancer

Objective： The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery （SRS） for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer. Methods： Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years （range, 32-85 years）. At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients （21.4%）, lobectomies in 30 （71.4%）, and wedge resection in 3 （7.2%）. 48 patients （90.5%） underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS. Results： There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients （28.3%） had no evidence of lymph node metastases （No）, 20 patients （37.7%） had hilar metastases （N1）, and 18 patients （34%） had mediastinal metastases （N2）. The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant （P〉0.05）. In lymph node negative patients （No）, the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases （N1-2）. The difference was significant （P〈0,01）. For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant （P〉0.05）. Conclusion： Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.

Implications of the autophagy core gene variations on brain metastasis risk in non-small cell lung cancer treated with EGFR-TKI

Objective The brain is the main site of failure in cancer patients with epidermal growth factor receptor(EGFR)mutations undergoing treatment.However,identifying patients who may develop brain metastases(BM)is difficult.Autophagy is critical for cancer initiation and progression.We hypothesized that genetic variants in autophagy core genes might contribute to BM risk of non-small cell lung cancer(NSCLC)following treatment with EGFR tyrosine kinase inhibitor(EGFR-TKIs).Methods We systematically examined 16 potentially functional genetic polymorphisms in seven autophagy core genes among 105 TKI-treated NSCLC patients.Kaplan-Meier curves were plotted to assess the cumulative BM probability.Univariate and multivariate Cox proportional hazard regression analyses were utilized to calculate hazard ratios(HRs)and 95%confidence intervals(CIs).We evaluated the potential associations of these genes with subsequent BM development.Results We found that ATG16L1:rs2241880,ATG10:rs10036653,rs3734114,and ATG3:rs7652377 are significantly associated with NSCLC treated with EGFR-TKIs(all P<0.05).BM developed more often in patients with ATG3 rs7652377 CC genotype(33%),ATG10 rs10036653 AA genotype(43%),ATG10:rs3734114 CT/CC genotype(46%),and ATG16L1 rs2241880 AA genotype(37%)compared to patients with AA genotypes at rs7652377(12%),AT/TT genotypes at rs10036653(16%),the TT genotype at rs3734114(13%),or AG/GG genotypes at rs2241880(17%).Conclusion These associations may be critical for understanding the role of autophagy in BM risk.Future prospective studies are needed to determine if prophylactic cranial irradiation(PCI)could offer a survival benefit in this group of patients.

Concurrent hepatocellular carcinoma metastasis to stomach,colon,and brain:A case report

BACKGROUND Extrahepatic metastasis(EHM)from hepatocellular carcinoma(HCC)occurs in 10%–15%of cases following initial treatment.The most frequent sites of EHM are the lung,lymph nodes,and bone.Gastrointestinal or brain metastasis from HCC is rarely reported.Here,we report a rare case of concurrent HCC metastases to the stomach,colon,and brain.CASE SUMMARY A 72-year-old male with a history of alcohol induced HCC presented with multiple intrahepatic recurrences and tumorous lesions in the stomach and ascending colon.Three years earlier,he underwent right hemihepatectomy,and 1 year ago,he had a video-assisted thoracoscopic wedge resection for pulmonary metastasis of HCC.We decided on surgical resection of the new metastases because of massive gastric bleeding and concern for possible colonic obstruction.The patient underwent gastric wedge resection and right hemicolectomy.Two weeks later,the patient developed dysarthria and mild cognitive disorder.Magnetic resonance imaging of the brain revealed a left frontal lobe lesion,and he underwent resection of a metastatic brain tumor.Unfortunately,he died 6 weeks after the last surgery due to hepatorenal syndrome.CONCLUSION Decision of surgery was carefully recommended in this case and may extend survival in other metastatic HCC patients with well-preserved hepatic function.