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 w...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.展开更多
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 difficul...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.展开更多
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...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.展开更多
Brain metastasis is a major cause of poor prognosis and high mortality for non-small cell lung cancer patients. The prognosis of non-small-cell lung cancer(NSCLC) patients with brain metastasis is generally poor and m...Brain metastasis is a major cause of poor prognosis and high mortality for non-small cell lung cancer patients. The prognosis of non-small-cell lung cancer(NSCLC) patients with brain metastasis is generally poor and more effective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.展开更多
BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastas...BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.展开更多
Brain(leptomeningeal) metastasis is one of the most common and severe complications of lung cancer. This article interprets expert consensus on the treatment advice for brain(leptomeningeal) metastasis of lung cancer,...Brain(leptomeningeal) metastasis is one of the most common and severe complications of lung cancer. This article interprets expert consensus on the treatment advice for brain(leptomeningeal) metastasis of lung cancer, expounding on its epidemiology, diagnostic standards, efficacy assessment, treatment advice, and other aspects.展开更多
Background:To explore risk factors and the efficacy of treatment strategies for brain metastasis (BM) in squamous cell carcinoma (SCC) of the lung.Methods:The clinical data of 188 pathologically confirmed as squamous ...Background:To explore risk factors and the efficacy of treatment strategies for brain metastasis (BM) in squamous cell carcinoma (SCC) of the lung.Methods:The clinical data of 188 pathologically confirmed as squamous cell carcinoma or adenosquamous carcinoma patients were studied retrospectively. Factors including age (<60 vs.≥60), gender, stage at diagnosis, T status (T1-2 vs. T3-4), N status (N0-1 vs. N2-3), histology (squamous vs. adenosquamous), smoking history (non-smoker vs. currentsmoker) and serum tumor markers (normal vs. elevated) were analyzed.Results:The incidence of BM was 19.1%(36/188) in our cohort. Patients who were female (p=0.005), had advanced disease at diagnosis (p<0.001), had adenosquamous carcinoma histology (p=0.033) or had elevated serum level of CEA at diagnosis (p<0.001) had significantly higher incidence of BM. In multivariate analysis, female (p=0.034, HR=18.874) and elevated serum level of CEA at diagnosis (p=0.009, HR=19.824) were independent risk factors of BM. BM patients who received additional systemic therapy after local therapy had significantly longer post-BM survival than those who received local therapy only (p=0.004, HR=0.058). Gemcitabine/platinum-containingregimen (GP) and taxans/platinum-containing regimen (TP) led to comparable brain-metastasis-free survival (BMFS) (p=0.10).Conclusions:Females and patients with elevated serum level of CEA at diagnosis had a higher risk of developing BM. The following systemic therapy after local therapy prolonged the survival of BM patient, but the efficacy of GP and TP was comparable in terms of preventing BM.展开更多
Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal g...Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of NSCLC.This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study.Methods:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion.Patients with asymptomatic,stable CNS metastases were included.Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every 12weeks.CNS responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,respectively.Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at baseline.No new safety findings were observed.Conclusions:These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases.展开更多
Background: Risk factors and treatments for brain metastasis (BM) in patients with adenocarcinoma have not been fully profiled in previous studies because of the enrolment of patients with tumours of mixed histology. ...Background: Risk factors and treatments for brain metastasis (BM) in patients with adenocarcinoma have not been fully profiled in previous studies because of the enrolment of patients with tumours of mixed histology. Thus, we specifically addressed the issue in patients with adenocarcinoma. Methods: Clinical data for 373 patients with pathologically confirmed adenocarcinoma were studied retrospectively. Factors including age (≤60 vs.>60), gender (male vs. female), stage at diagnosis, T status (T1-2 vs. T3-4), N status (N0-1 vs. N2-3), epidermal growth factor receptor (EGFR) mutation status (wild-type vs. mutant) and smoking status (never vs. current) were analyzed. Results: In multivariate analysis, age (P=0.006) and N status (P=0.041) were independent risk factors for BM. In patients with BM, adding systemic therapy to local therapy improved median post-brain-metastasis survival (mPBMS) (P=0.02). However, if stratification was conducted according to the recursive partitioning analysis (RPA) classification or graded prognostic assessment (GPA) scoring, only patients in RPA class Ⅱ (P=0.020) or with GPA score 1.5-2.5 (P=0.032) could benefit from local plus systemic therapy. Those who received both pemetrexed and tyrosine kinase inhibitors (TKIs) as systemic therapies had a longer mPBMS than those who received TKIs alone, regardless of whether local therapy was applied. In patients with EGFR-sensitive mutations, TKIs therapy led to a longer mPBMS than conventional chemotherapy (P=0.002). Conclusions: Adenocarcinoma patients who were younger than 60 years of age and those with N2-3 disease have a significantly higher risk of BM. The addition of systemic therapy to local therapy can significantly prolong mPBMS, but the survival benefit confined in certain populations. Patients with opportunity to receive both pemetrexed and TKIs had the longest mPBMS.展开更多
Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy amo...Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy among patients presenting with intracranial lesions are limited.This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.Methods:Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable,asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1,2019 and September 30,2021.The patients were stratified into two groups according to the first-line treatment regimen received:ICI combined with chemotherapy(n=102)or chemotherapy(n=109).Systemic and intracranial objective response rates(ORRs)and progression-free survival(PFS)were analyzed.Adverse events were also compared between the groups.Results:Compared with the chemotherapy-based regimen,the ICI-containing regimen was associated with a significantly higher intracranial(44.1%[45/102]vs.28.4%[31/109],χ^(2)=5.620,P=0.013)and systemic(49.0%[50/102]vs.33.9%[37/109],χ^(2)=4.942,P=0.019)ORRs and longer intracranial(11.0 months vs.7.0 months,P<0.001)and systemic(9.0 months vs.5.0 months,P<0.001)PFS.Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS(hazard ratio[HR]=0.52,95%confidence interval[CI]:0.37-0.73,P<0.001)and systemic PFS(HR=0.48,95%CI:0.35-0.66,P<0.001).No unexpected serious adverse effects were observed.Conclusion:Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registration:https://www.clinicaltrials.gov/,OMESIA,NCT05129202.展开更多
文摘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.
基金Supported by a grant from the National Natural Science Foundation of China(No.81502521).
文摘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.
文摘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.
文摘Brain metastasis is a major cause of poor prognosis and high mortality for non-small cell lung cancer patients. The prognosis of non-small-cell lung cancer(NSCLC) patients with brain metastasis is generally poor and more effective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.
基金Yu-Qing Xia Famous Old Chinese Medicine Heritage Workshop of“3+3”Project of Traditional Chinese Medicine Heritage in Beijing,Jing Zhong Yi Ke Zi(2021),No.73National Natural Science Foundation of China,No.81973640+1 种基金Nursery Program of Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine,No.WJYY-YJKT-2022-05China Academy of Traditional Chinese Medicine Wangjing Hospital High-Level Chinese Medicine Hospital Construction Project Chinese Medicine Clinical Evidence-Based Research:The Evidence-Based Research of Electrothermal Acupuncture for Relieving Cancer-Related Fatigue in Patients With Malignant Tumor,No.WYYY-XZKT-2023-20.
文摘BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.
文摘Brain(leptomeningeal) metastasis is one of the most common and severe complications of lung cancer. This article interprets expert consensus on the treatment advice for brain(leptomeningeal) metastasis of lung cancer, expounding on its epidemiology, diagnostic standards, efficacy assessment, treatment advice, and other aspects.
文摘Background:To explore risk factors and the efficacy of treatment strategies for brain metastasis (BM) in squamous cell carcinoma (SCC) of the lung.Methods:The clinical data of 188 pathologically confirmed as squamous cell carcinoma or adenosquamous carcinoma patients were studied retrospectively. Factors including age (<60 vs.≥60), gender, stage at diagnosis, T status (T1-2 vs. T3-4), N status (N0-1 vs. N2-3), histology (squamous vs. adenosquamous), smoking history (non-smoker vs. currentsmoker) and serum tumor markers (normal vs. elevated) were analyzed.Results:The incidence of BM was 19.1%(36/188) in our cohort. Patients who were female (p=0.005), had advanced disease at diagnosis (p<0.001), had adenosquamous carcinoma histology (p=0.033) or had elevated serum level of CEA at diagnosis (p<0.001) had significantly higher incidence of BM. In multivariate analysis, female (p=0.034, HR=18.874) and elevated serum level of CEA at diagnosis (p=0.009, HR=19.824) were independent risk factors of BM. BM patients who received additional systemic therapy after local therapy had significantly longer post-BM survival than those who received local therapy only (p=0.004, HR=0.058). Gemcitabine/platinum-containingregimen (GP) and taxans/platinum-containing regimen (TP) led to comparable brain-metastasis-free survival (BMFS) (p=0.10).Conclusions:Females and patients with elevated serum level of CEA at diagnosis had a higher risk of developing BM. The following systemic therapy after local therapy prolonged the survival of BM patient, but the efficacy of GP and TP was comparable in terms of preventing BM.
基金Hansoh Pharmaceutical Group Co.LtdNational Natural Science Foundation of China,Grant/Award Numbers:82030045,82241227+3 种基金National Multi-disciplinary Treatment Project for Major Diseases,Grant/Award Number:2020NMDTPCollaborative Innovation Center for Clinical and Translational Science by Ministry of Education&Shanghai,Grant/Award Numbers:CCTS-202204,CCTS-202304Shanghai Chest Hospital Basic Research Project,Grant/Award Number:2023YNKT-1Pujiang Program,Grant/Award Number:22PJ1420700。
文摘Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of NSCLC.This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study.Methods:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion.Patients with asymptomatic,stable CNS metastases were included.Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every 12weeks.CNS responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,respectively.Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at baseline.No new safety findings were observed.Conclusions:These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases.
文摘Background: Risk factors and treatments for brain metastasis (BM) in patients with adenocarcinoma have not been fully profiled in previous studies because of the enrolment of patients with tumours of mixed histology. Thus, we specifically addressed the issue in patients with adenocarcinoma. Methods: Clinical data for 373 patients with pathologically confirmed adenocarcinoma were studied retrospectively. Factors including age (≤60 vs.>60), gender (male vs. female), stage at diagnosis, T status (T1-2 vs. T3-4), N status (N0-1 vs. N2-3), epidermal growth factor receptor (EGFR) mutation status (wild-type vs. mutant) and smoking status (never vs. current) were analyzed. Results: In multivariate analysis, age (P=0.006) and N status (P=0.041) were independent risk factors for BM. In patients with BM, adding systemic therapy to local therapy improved median post-brain-metastasis survival (mPBMS) (P=0.02). However, if stratification was conducted according to the recursive partitioning analysis (RPA) classification or graded prognostic assessment (GPA) scoring, only patients in RPA class Ⅱ (P=0.020) or with GPA score 1.5-2.5 (P=0.032) could benefit from local plus systemic therapy. Those who received both pemetrexed and tyrosine kinase inhibitors (TKIs) as systemic therapies had a longer mPBMS than those who received TKIs alone, regardless of whether local therapy was applied. In patients with EGFR-sensitive mutations, TKIs therapy led to a longer mPBMS than conventional chemotherapy (P=0.002). Conclusions: Adenocarcinoma patients who were younger than 60 years of age and those with N2-3 disease have a significantly higher risk of BM. The addition of systemic therapy to local therapy can significantly prolong mPBMS, but the survival benefit confined in certain populations. Patients with opportunity to receive both pemetrexed and TKIs had the longest mPBMS.
基金support from the National Natural Science Foundation of China(Nos.82003206 and 82173338)Natural Science Foundation of Hunan Province(Nos.2020SK2031,2020SK2030,2021RC4040,and 2020JJ3025).
文摘Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy among patients presenting with intracranial lesions are limited.This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.Methods:Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable,asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1,2019 and September 30,2021.The patients were stratified into two groups according to the first-line treatment regimen received:ICI combined with chemotherapy(n=102)or chemotherapy(n=109).Systemic and intracranial objective response rates(ORRs)and progression-free survival(PFS)were analyzed.Adverse events were also compared between the groups.Results:Compared with the chemotherapy-based regimen,the ICI-containing regimen was associated with a significantly higher intracranial(44.1%[45/102]vs.28.4%[31/109],χ^(2)=5.620,P=0.013)and systemic(49.0%[50/102]vs.33.9%[37/109],χ^(2)=4.942,P=0.019)ORRs and longer intracranial(11.0 months vs.7.0 months,P<0.001)and systemic(9.0 months vs.5.0 months,P<0.001)PFS.Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS(hazard ratio[HR]=0.52,95%confidence interval[CI]:0.37-0.73,P<0.001)and systemic PFS(HR=0.48,95%CI:0.35-0.66,P<0.001).No unexpected serious adverse effects were observed.Conclusion:Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registration:https://www.clinicaltrials.gov/,OMESIA,NCT05129202.
文摘目的探讨小分子酪氨酸激酶抑制剂(Tyrosine kinase inhibitor,TKI)联合同期放疗治疗晚期非小细胞肺癌脑转移患者的近期效果。方法回顾性分析2017年1月至2019年1月我院71例晚期非小细胞肺癌脑转移患者的临床资料。根据治疗方法分组,以采用全脑放疗治疗的34例患者为对照组,以采用小分子TKI联合同期放疗的37例患者为研究组。比较两组近期效果、生活质量(Quality of life,QOL)评分及不良反应。结果治疗后,研究组脑转移灶疾病控制率(72.97%)高于对照组(47.06%)(P<0.05);研究组QOL评分高于对照组(P<0.05);两组恶心呕吐、腹泻、皮疹、疲倦乏力、骨髓抑制、肝肾功能损伤等不良反应发生率比较差异无统计学意义(P>0.05)。结论晚期非小细胞肺癌脑转移治疗中联用小分子TKI吉非替尼、同期放疗可增强近期疗效,改善患者生活质量,且不良反应少。