BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Objective:To investigate the role of the Brock, Mayo, and PKUPH combined model in risk stratification of solitary pulmonary nodules (SPNs) in health check-up population.Methods:An ambispective cohort study was conducted on 668 eligible SPNs cases from the health management center in Chongqing General Hospital from June 2018 to June 2019. The exposure condition was prospectively followed or historically retrospected, and the clinical outcomes were prospectively followed. SPNs were classified into benign and malignant groups. Descriptive statistics and univariate analysis were performed to assess the differences in risk characteristics between two groups. Receiver operating characteristic (ROC) curve, clinical decision curve, and Hosmer-Lemeshow goodness-of-fit test were used to evaluate and compare the predictive performance, clinical utility, and calibration of the combined model versus individual Brock, Mayo, and PKUPH models.Results:Among the 668 SPNs cases, 82 (12.28%) were diagnosed as malignant. Age, sex, smoking history, extrapulmonary tumor history, diameter, upper lobe, clear border and spicule sign in the malignant group were significantly different from those in the benign group (all P<0.05). The combined model demonstrated superior predictive performance, clinical utility, and calibration compared to the best-performing individual Brock model [Area under the curve (AUC): 0.88 (95% CI: 0.84-0.92) vs 0.86 (95% CI: 0.82-0.91)]. Besides, multi-grade risk stratification enabled by the combined model was better than binary classification, with the malignant rate of the four risk levels were 0.60%, 4.62%, 14.58% and 56.07%, respectively. Conclusion:The combined model addresses the limitations of individual models in SPNs risk stratification for health examination populations, improving predictive performance, clinical utility, and calibration, while proposing a superior multi-grade risk stratification system.

Objective:To evaluate the predictive efficacy of different comorbidity indices for hospitalization due to acute exacerbations in chronic obstructive pulmonary disease (COPD) patients with comorbidities (CO-COPD).Methods:This retrospective cohort study included 259 stable COPD patients with comorbidities from Beijing Tongren Hospital, Capital Medical University, between October 2021 and September 2023, all with ≥1-year follow-up. Patients were categorized into hospitalized ( n=75) and non-hospitalized ( n=184) groups based on acute exacerbation events. Clinical characteristics, comorbidities, and comorbidity indices, including Charlson Comorbidity Index (CCI), COPD-specific Comorbidity Test (COTE), and comorbidities in chronic obstructive lung disease index (COMCOLD) were compared between two goups. Risk facors of hospitalization due to acute exacerbations were analyzed by Cox regression. Modified indices were developed by incorporating additional respiratory comorbidities (asthma, bronchiectasis, lung cancer) weighted by hazard ratios (HRs) from Cox reguression. The predictive performance of different comorbidity indices for hospitalization was assessed by receiver operating characteristic (ROC) curves. Results:Hospitalized patients exhibited lower BMI, FEV 1% predicted, and FEV 1/FVC (all P<0.05), alongside higher modified British Medical Research Coucil (mMRC) scores and COPD assessment test (CAT) scores, eosinophil counts, and Global Initiative for Chronic Obstructive Lung Disease, (GOLD)severity ( t=3.73, Z=-3.43, Z=-2.43, Z=-11.10, Z=-11.32, Z=-1.80, χ2=17.62, all P<0.05); and also higher use rates of inhaled corticosteroid (ICS) and systemic oral corticosteroid (OCS) ( χ2=5.48, 7.15, all P<0.05). The comorbidities of asthma, bronchiectasis, lung cancer, hypertension, coronary atherosclerotic heart disease, anxiety and depression in hospitalized group were significantly higher ( χ2=22.49, 18.30, 15.63, 5.10, 4.68, 7.46, 5.16, all P<0.05), along with the increased CCI and COTE index ( P<0.05). Comorbid asthma, bronchiectasis, and lung cancer were independent risk factors for hospitalization ( HR=1.841, 2.924, and 2.076, respectively; all P<0.05). Original CCI and COTE showed moderate predictive value ( AUC=0.609 and 0.655), while modified CCI, COTE, and COMCOLD demonstrated improved performance ( AUC=0.730, 0.760, and 0.713, respectively). At optimal cutoffs (modified CCI>3.5, COTE>4.5, COMCOLD>6.5), sensitivities were 61.3%, 76.0%, and 58.7%, with specificities of 70.1%, 61.4%, and 72.3%. Age-stratified analysis revealed enhanced predictive utility of modified indices across age groups. Conclusions:CCI, COTE, and COMCOLD provide modest predictive value for hospitalization in CO-COPD. Modified indices incorporating respiratory comorbidities significantly improve risk stratification, offering clinical utility for identifying high-risk patients in primary care settings.

Objective:To investigate the role of the Brock, Mayo, and PKUPH combined model in risk stratification of solitary pulmonary nodules (SPNs) in health check-up population.Methods:An ambispective cohort study was conducted on 668 eligible SPNs cases from the health management center in Chongqing General Hospital from June 2018 to June 2019. The exposure condition was prospectively followed or historically retrospected, and the clinical outcomes were prospectively followed. SPNs were classified into benign and malignant groups. Descriptive statistics and univariate analysis were performed to assess the differences in risk characteristics between two groups. Receiver operating characteristic (ROC) curve, clinical decision curve, and Hosmer-Lemeshow goodness-of-fit test were used to evaluate and compare the predictive performance, clinical utility, and calibration of the combined model versus individual Brock, Mayo, and PKUPH models.Results:Among the 668 SPNs cases, 82 (12.28%) were diagnosed as malignant. Age, sex, smoking history, extrapulmonary tumor history, diameter, upper lobe, clear border and spicule sign in the malignant group were significantly different from those in the benign group (all P<0.05). The combined model demonstrated superior predictive performance, clinical utility, and calibration compared to the best-performing individual Brock model [Area under the curve (AUC): 0.88 (95% CI: 0.84-0.92) vs 0.86 (95% CI: 0.82-0.91)]. Besides, multi-grade risk stratification enabled by the combined model was better than binary classification, with the malignant rate of the four risk levels were 0.60%, 4.62%, 14.58% and 56.07%, respectively. Conclusion:The combined model addresses the limitations of individual models in SPNs risk stratification for health examination populations, improving predictive performance, clinical utility, and calibration, while proposing a superior multi-grade risk stratification system.

Objective:To evaluate the predictive efficacy of different comorbidity indices for hospitalization due to acute exacerbations in chronic obstructive pulmonary disease (COPD) patients with comorbidities (CO-COPD).Methods:This retrospective cohort study included 259 stable COPD patients with comorbidities from Beijing Tongren Hospital, Capital Medical University, between October 2021 and September 2023, all with ≥1-year follow-up. Patients were categorized into hospitalized ( n=75) and non-hospitalized ( n=184) groups based on acute exacerbation events. Clinical characteristics, comorbidities, and comorbidity indices, including Charlson Comorbidity Index (CCI), COPD-specific Comorbidity Test (COTE), and comorbidities in chronic obstructive lung disease index (COMCOLD) were compared between two goups. Risk facors of hospitalization due to acute exacerbations were analyzed by Cox regression. Modified indices were developed by incorporating additional respiratory comorbidities (asthma, bronchiectasis, lung cancer) weighted by hazard ratios (HRs) from Cox reguression. The predictive performance of different comorbidity indices for hospitalization was assessed by receiver operating characteristic (ROC) curves. Results:Hospitalized patients exhibited lower BMI, FEV 1% predicted, and FEV 1/FVC (all P<0.05), alongside higher modified British Medical Research Coucil (mMRC) scores and COPD assessment test (CAT) scores, eosinophil counts, and Global Initiative for Chronic Obstructive Lung Disease, (GOLD)severity ( t=3.73, Z=-3.43, Z=-2.43, Z=-11.10, Z=-11.32, Z=-1.80, χ2=17.62, all P<0.05); and also higher use rates of inhaled corticosteroid (ICS) and systemic oral corticosteroid (OCS) ( χ2=5.48, 7.15, all P<0.05). The comorbidities of asthma, bronchiectasis, lung cancer, hypertension, coronary atherosclerotic heart disease, anxiety and depression in hospitalized group were significantly higher ( χ2=22.49, 18.30, 15.63, 5.10, 4.68, 7.46, 5.16, all P<0.05), along with the increased CCI and COTE index ( P<0.05). Comorbid asthma, bronchiectasis, and lung cancer were independent risk factors for hospitalization ( HR=1.841, 2.924, and 2.076, respectively; all P<0.05). Original CCI and COTE showed moderate predictive value ( AUC=0.609 and 0.655), while modified CCI, COTE, and COMCOLD demonstrated improved performance ( AUC=0.730, 0.760, and 0.713, respectively). At optimal cutoffs (modified CCI>3.5, COTE>4.5, COMCOLD>6.5), sensitivities were 61.3%, 76.0%, and 58.7%, with specificities of 70.1%, 61.4%, and 72.3%. Age-stratified analysis revealed enhanced predictive utility of modified indices across age groups. Conclusions:CCI, COTE, and COMCOLD provide modest predictive value for hospitalization in CO-COPD. Modified indices incorporating respiratory comorbidities significantly improve risk stratification, offering clinical utility for identifying high-risk patients in primary care settings.

Objective:To investigate the clinical features of patients with chronic obstructive pulmonary disease (COPD) and serum-positive specific IgE (SIgE).Methods:This study was a retrospective cohort study. A total of 105 stable COPD patients with allergic features and completed serum SIgE testing were included, and all of them were from Capital Medical University, Beijing Tong Ren Hospital from September 2022 to October 2023. Those with at least one positive result of SIgE testing were classified as positive SIgE COPD group, and those with negative SIgE were classified as negative SIgE COPD group. There were 32 cases (30.5%) in the positive SIgE COPD group and 73 cases (69.5%) in the negative SIgE COPD group. Differences in laboratory tests, pulmonary function, chronic obstructive pulmonary symptom scores, incidence of severe acute exacerbation events in the past year, and drug therapy were compared between the two groups. The risk factors for positive SIgE COPD were analyzed, and the best predictive value for the diagnosis of positive SIgE COPD was analyzed using the area under the curve (AUC) of receiver operating characteristic (ROC).Results:Compared with the negative SIgE COPD group, the percentage of positive SIgE COPD group with rhinitis, sinusitis, sinusitis with nasal polyps, eczema, and a history of drug or food allergy were higher (all P<0.05) and the percentage of those who had quit smoking were higher ( P<0.05); the percentage of IgE above normal thresholds, the level of IgE, the percentage of peripheral blood eosinophil (EOS%), the count of EOS, and fractional exhaled nitric oxide (FeNO) were higher (all P<0.05), and the percentage of those who had severe and above severe Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) pulmonary function classification were higher, while the percentage of forced expiratory volume in one second (FEV 1% predicted), 25% maximal expiratory flow (MEF 25%) and MEF 75/25% were lower, and FEV 1/FVC was higher (all P<0.05). The positive SIgE COPD group had higher modified British medical research council (mMRC) scores and COPD assessment test (CAT) scores, and a higher incidence of severe acute exacerbation events over the past year (all P<0.05), and the use of short-acting β 2 receptor agonists (SABA) or short-acting muscarinic antagonist (SAMA), inhaled corticosteroid (ICS), theophylline and oral hormone therapy were more frequent (all P<0.05). EOS% ( OR=1.252, 95% CI: 1.039-1.508) was a risk factor for SIgE positivity in COPD ( P<0.05), and having quit smoking ( OR=0.385, 95% CI: 0.197-0.751) was a protective factor ( P<0.05). The AUC value of the ROC curve of EOS%>2.5% for the diagnosis of SIgE positivity was 0.647 (95% CI: 0.543-0.752), with a sensitivity and specificity of 52.8% and 73.1%, respectively. Conclusions:Positive SIgE COPD has sever clinical symptoms, high risk of acute exacerbation and deficiencies in treatment. The elevate of EOS% is a risk factor for the development of positive SIgE in COPD patients; positive SIgE COPD meets the diagnostic criteria for allergic COPD phenotype, and EOS% over 2.5% is suggestive of the clinical detection of allergic COPD phenotype.

Cancer of unknown primary(CUP)refers to a group of histopathologically confirmed malignancies that cannot be identified in terms of their primary origin despite thorough investigations.CUP accounts for approximately 3%-5%of all newly diagnosed cancers worldwide,with an overall survival(OS)ranging from 2.7 to 16.0 months.CUP has long been a significant scientific challenge due to the elusive nature and heterogeneity of the primary sites.In the era of immunohistochemistry(IHC),IHC has been applied to identify the primary site in approximately 70%of CUP cases.However,IHC also has limitations for undifferentiated cancers of unknown primary,and results can be influenced by experimental and human factors.In recent years,with the development of molecular tumor profiling(MTP),techniques such as cytology,histology,gene expression profiling(GEP),genomics and epigenomics have been able to accurately detect the primary site in 90%of cases.Currently,the 90-gene tumor tissue origin test has been proven to have an accuracy rate of 94.4%in diagnosing the primary site of CUP,laying the foundation for precision treatment.In the past,platinum and taxane-based empirical chemotherapy was commonly used for treating CUP.However,these treatments did not yield significant improvements in patient survival and prognosis.Since 2008,there has been a global emergence of clinical studies on MTP-guided first-line therapy for CUP.However,due to study design flaws and result controversies,there is no international consensus on the superiority of organ-specific treatment over empirical chemotherapy in terms of improving progression-free survival(PFS)and OS for CUP.Based on this,our center conducted the world's first phase Ⅲ clinical trial in 2017,and demonstrated improved PFS and favorable OS by GEP-guided site-specific therapy of CUP,which established the primacy of site-specific first-line therapy for CUP.In this review,we detailed the epidemiology,pathogenesis,clinical characteristics and the progression of CUP diagnosis from the era of IHC to MTP.Furthermore,we reviewed the advancements in CUP treatment from empirical chemotherapy to MTP-guided organ-specific treatment.Additionally,this review delved into the exploration of second-line treatment options and the establishment of a clinical stratified management model,which are two topics in future research of CUP.This review aimed to summarize the progress in the diagnosis and treatment of CUP,further explore future research directions for CUP,and improve the survival and prognosis of patients with CUP.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

Cancer of unknown primary(CUP)refers to a group of histopathologically confirmed malignancies that cannot be identified in terms of their primary origin despite thorough investigations.CUP accounts for approximately 3%-5%of all newly diagnosed cancers worldwide,with an overall survival(OS)ranging from 2.7 to 16.0 months.CUP has long been a significant scientific challenge due to the elusive nature and heterogeneity of the primary sites.In the era of immunohistochemistry(IHC),IHC has been applied to identify the primary site in approximately 70%of CUP cases.However,IHC also has limitations for undifferentiated cancers of unknown primary,and results can be influenced by experimental and human factors.In recent years,with the development of molecular tumor profiling(MTP),techniques such as cytology,histology,gene expression profiling(GEP),genomics and epigenomics have been able to accurately detect the primary site in 90%of cases.Currently,the 90-gene tumor tissue origin test has been proven to have an accuracy rate of 94.4%in diagnosing the primary site of CUP,laying the foundation for precision treatment.In the past,platinum and taxane-based empirical chemotherapy was commonly used for treating CUP.However,these treatments did not yield significant improvements in patient survival and prognosis.Since 2008,there has been a global emergence of clinical studies on MTP-guided first-line therapy for CUP.However,due to study design flaws and result controversies,there is no international consensus on the superiority of organ-specific treatment over empirical chemotherapy in terms of improving progression-free survival(PFS)and OS for CUP.Based on this,our center conducted the world's first phase Ⅲ clinical trial in 2017,and demonstrated improved PFS and favorable OS by GEP-guided site-specific therapy of CUP,which established the primacy of site-specific first-line therapy for CUP.In this review,we detailed the epidemiology,pathogenesis,clinical characteristics and the progression of CUP diagnosis from the era of IHC to MTP.Furthermore,we reviewed the advancements in CUP treatment from empirical chemotherapy to MTP-guided organ-specific treatment.Additionally,this review delved into the exploration of second-line treatment options and the establishment of a clinical stratified management model,which are two topics in future research of CUP.This review aimed to summarize the progress in the diagnosis and treatment of CUP,further explore future research directions for CUP,and improve the survival and prognosis of patients with CUP.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.