RESUMO
OBJECTIVES: The prognosis of patients with Small Cell Lung Cancer (SCLC) can be predicted by their Lymph Node (LN) status. The authors aimed to assess the correlations between SCLC survival and number of LN Ratio (LNR), positive LN (pLNs), and Logarithmic Odds of positive LN (LODDS). METHODS: This cohort study retrospectively included 1,762 patients with SCLC from the SEER database 2004â2015. The X-tile software was used to determine the cutoff values for pLNs, LNR, and LODDS. The correlations between pLNs, LNR, and LODDS with Overall Survival (OS) and Cancer-Specific Survival (CSS) were explored using Cox regression analysis. The study used the C-index to assess the predictive value of LNR, pLNs, and LODDS on survival. RESULTS: Among these 1,762 patients, 121 (6.87%) were alive, 1,641 (93.13%) died, and 1,532 (86.95%) died of SCLC. In univariable COX analysis, LNR, pLNs, and LODDS all showed a correlation with CSS and OS (p < 0.05). In multivariable COX analysis, only patients with LODDS (> 0.3 vs. ≤ 0.3) were related to both worse OS (HR = 1.28, 95% CI 1.10â1.50) and CSS (HR = 1.29, 95% CI 1.10â1.51), but no correction was observed between LNR and pLNs and survival (p > 0.05). The C-indices for predicting OS for LODDS were 0.552 (95% CI 0.541â0.563), for LNR 0.504 (95% CI 0.501â0.507), and for pLNs 0.527 (95% CI 0.514â0.540). Moreover, the association between LODDS and prognosis in SCLC patients was significant only in patients with LN stage N1 and N2, but not in stage N3. CONCLUSION: LODDS may be better than other LN assessment tools at predicting survival in SCLC patients.
Assuntos
Neoplasias Pulmonares , Linfonodos , Metástase Linfática , Programa de SEER , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Masculino , Feminino , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Linfonodos/patologia , Prognóstico , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Adulto , Estimativa de Kaplan-MeierRESUMO
BACKGROUND: The application of immune checkpoint inhibitors (ICIs) in treating patients with extensive-stage small-cell lung cancer (ES-SCLC) has brought us new hope, but the real-world outcome is relatively lacking. Our aim was to investigate the clinical use, efficacy, and survival benefit of ICIs in ES-SCLC from real-world data analysis. METHODS: A retrospective analysis of ES-SCLC patients was conducted between 2012 and 2022. Progression-free survival (PFS) and overall survival (OS) were assessed between groups to evaluate the value of ICIs at different lines of treatment. PFS1 was defined as the duration from initial therapy to disease progression or death. PFS2 was defined as the duration from the first disease progression to the second disease progression or death. RESULTS: One hundred and eighty patients with ES-SCLC were included. We performed landmark analysis, which showed that compared to the second-line and subsequent-lines ICIs-combined therapy group (2SL-ICIs) and non-ICIs group, the first-line ICIs-combined therapy group (1L-ICIs) prolonged OS and PFS1. There was a trend toward prolonged OS in the 2SL-ICIs group than in the non-ICIs group, but the significance threshold was not met (median OS 11.94 months vs. 11.10 months, P = 0.14). A longer PFS2 was present in the 2SL-ICIs group than in the non-ICIs group (median PFS2 4.13 months vs. 2.60 months, P < 0.001). CONCLUSION: First-line ICIs plus chemotherapy should be applied in clinical practice. If patients did not use ICIs plus chemotherapy in first-line therapy, the use of ICIs in the second line or subsequent lines of treatment could prolong PFS2.
Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Intervalo Livre de Progressão , Carcinoma de Pequenas Células do Pulmão , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Estudos Retrospectivos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Taxa de SobrevidaRESUMO
PURPOSE: Although immunotherapy improves outcomes in extensive-stage small-cell lung cancer (ES-SCLC), the search for biomarkers predicting treatment success is crucial. Natural killer (NK) cells are potential indicators in various cancers, however, their precise role in ES-SCLC prognosis remains unclear. METHODS: In this retrospective study, 33 patients with ES-SCLC treated with first-line immuno-chemotherapy were enrolled. The peripheral NK cell percentage and its longitudinal dynamics were analyzed using flow cytometry. Progression-free survival (PFS) and overall survival (OS) were calculated as hazard ratio (HR) and compared statistically. RESULTS: The median PFS was better in the group with normal baseline NK cell levels than the low group (7.0 vs. 4.6 months; HR = 0.17; 95% CI 0.07-0.41; P < 0.0001), but there was no association with OS (14.9 vs. 10.3 months; HR = 0.55; 95% CI 0.23-1.31; P = 0.171). Furthermore, the NK cell% for 95.0% of patients increased after immunochemotherapy in the clinical response group (P = 0.0047), which led to a better median PFS (6.3 vs. 2.1 months; HR = 0.23; 95% CI 0.05-0.98; P < 0.0001) and OS (14.9 vs. 5.9 months; HR = 0.20; 95% CI 0.04-1.02; P < 0.0001). Similar trends were observed with NK cell% changes up to disease progression, improving PFS (6.5 vs. 4.3; HR = 0.41; 95% CI 0.12-0.92; P = 0.0049) and OS (17.4 vs. 9.7; HR = 0.42; 95% CI 0.17-1.02; P < 0.0001). CONCLUSION: In patients with ES-SCLC, the percentage and changes in peripheral NK cells can predict the response to combined immunotherapy and chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Imunoterapia , Células Matadoras Naturais , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Masculino , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/imunologia , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia/métodos , Intervalo Livre de Progressão , Prognóstico , Adulto , Estadiamento de Neoplasias , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Anlotinib, as a salvage treatment for patients after failure of third-line or later-line treatments for small cell lung cancer (SCLC), has shown efficacy in patients with brain metastases (BMs). However, the efficacy and safety of anlotinib alone or in combination with immunotherapy for SCLC with BMs remain unclear. METHOD: Patients treated with anlotinib alone or in combination with an immune checkpoint inhibitor (ICI) at the Zhejiang Cancer Hospital between April 2019 and February 2023 were identified. Kaplan-Meier curves were used to describe the progression-free survival (PFS) and intracranial PFS (iPFS). A waterfall diagram was used to indicate changes in intracranial lesions. RESULTS: A total of 48 patients were included; 29 received anlotinib alone, and 19 were administered anlotinib plus ICI. Combination therapy, compared with anlotinib, was associated with significantly longer PFS and iPFS (PFS: 8.1 months vs. 2.5 months, P < 0.001; iPFS: 8.1 months vs. 2.5 months, P = 0.004). Similar results were observed in patients with multiple BMs (PFS: 8.1 months vs. 1.9 months, P = 0.001; iPFS: 8.1 months vs. 1.9 months, P = 0.002). After third-line or later-line treatments, patients treated with ICI plus anlotinib also achieved significant PFS and iPFS benefits (PFS: 8.4 months vs. 2.1 months, P < 0.001; iPFS: 9.2 months vs. 2.1 months, P = 0.002). No new or severe adverse events were observed with combination therapy. CONCLUSION: The combination of anlotinib and ICI has promising intracranial and extracranial efficacy with tolerable toxicity, and may be a therapeutic option for SCLC patients with BMs.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas , Inibidores de Checkpoint Imunológico , Indóis , Neoplasias Pulmonares , Quinolinas , Carcinoma de Pequenas Células do Pulmão , Humanos , Indóis/uso terapêutico , Indóis/administração & dosagem , Indóis/efeitos adversos , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/administração & dosagem , Masculino , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Estimativa de Kaplan-MeierRESUMO
PURPOSE: A previous real-world study conducted in China confirmed that first-line atezolizumab, in combination with etoposide/platinum (EP), leads to significantly longer progression-free survival (PFS) compared to EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC). The present study aimed to provide updated survival outcome data and evaluate the clinical efficacy of atezolizumab plus chemotherapy in ES-SCLC patients with brain metastasis (BM). METHODS: This retrospective study included 225 patients with ES-SCLC who were treated with EP alone (EP group) or a combination of EP + atezolizumab (atezolizumab group). Survival outcomes for the total study sample and patients in the BM subgroup were estimated using the Kaplan-Meier method. RESULTS: The atezolizumab group continued to demonstrate significantly longer PFS than the EP group (hazard ratio [HR], 0.68). The median overall survival (OS) was 26.2 months in the atezolizumab group vs. 14.8 months in the EP group (HR, 0.63). Additionally, among the BM patients in our study, the median PFS was found to be longer in the atezolizumab group (7.0 months) than in the EP group (4.1 months) (HR, 0.46). The OS of the BM patients did not differ significantly between the two treatment groups. CONCLUSIONS: The addition of atezolizumab to EP as a first-line treatment for ES-SCLC was found to improve survival outcomes. This treatment combination may also prolong PFS in patients with BM, regardless of the administration of cranial irradiation. However, among the BM patients in our study, there was no significant difference in OS between the two treatment groups.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas , Etoposídeo , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Idoso , Adulto , Intervalo Livre de Progressão , Estimativa de Kaplan-Meier , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Taxa de Sobrevida , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Although it has been shown that cyclin dependent kinase inhibitor 2A (CDKN2A) plays a significant role in a number of malignancies, its clinicopathological value and function in small cell lung cancer (SCLC) is unclear and warrants additional research. METHODS: The clinical significance of CDKN2A expression in SCLC was examined by multiple methods, including comprehensive integration of mRNA level by high throughput data, Kaplan-Meier survival analysis for prognostic value, and validation of its protein expression using in-house immunohistochemistry. RESULTS: The expression of CDKN2A mRNA in 357 cases of SCLC was evidently higher than that in the control group (n = 525) combing the data from 20 research centers worldwide. The standardized mean difference (SMD) was 3.07, and the area under the curve (AUC) of summary receiver operating characteristic curve (sROC) was 0.97 for the overexpression of CDKN2A. ACC, COAD, KICH, KIRC, PCPG, PRAD, UCEC, UVM patients with higher CDKN2A expression had considerably worse overall survival rates than those with lower CDKN2A expression with the hazard ratio (HR) > 1. CONCLUSION: CDKN2A upregulation extensively enhances the carcinogenesis and progression of SCLC.
Assuntos
Biomarcadores Tumorais , Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/mortalidade , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Prognóstico , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Feminino , Masculino , Estimativa de Kaplan-Meier , Curva ROC , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pessoa de Meia-Idade , Taxa de Sobrevida , Estudos Prospectivos , Idoso , Estudos de Casos e Controles , Relevância ClínicaRESUMO
BACKGROUND: Small cell lung cancer (SCLC) is an extremely malignant subtype of lung cancer because of its high potential for metastases. Cardiac invasion of SCLC is a serious concern that may lead to systemic embolism or tract obstruction. It has aroused much concern that cardiovascular comorbidities may significantly affect the survival of SCLC patients and their treatment decisions. METHODS: We consecutively recruited 772 small cell lung cancer (SCLC) patients between January 2011 and December 2018 from 4 cancer specialty hospitals in China. Only newly diagnosed primary cancer inpatients were included. Univariable and multivariable adjusted Cox proportional hazard models were conducted to evaluate the risk factors associated with mortality. Hazard ratios (HRs) for mortality and corresponding 95% confidence intervals (95% CIs) were calculated. RESULTS: The prevalence of cardiovascular diseases (CVDs) was 34.6% in all SCLC patients. Log-rank analysis presented statistically significant differences in median survival time (MST) between patients with CVD and without CVD in all SCLC patients (9.0 months vs. 15.0 months, P = 0.005) and patients with chemotherapy only (12.0 months vs. 18.0 months, P = 0.048). Pericardial effusion (HR 1.671, 95% CI 1.082-2.580, P = 0.021) and heart failure (HR 1.752, 95% CI 1.290-2.379, P < 0.001) were independent risk factors associated with mortality in all SCLC patients. VTE is related to poorer prognosis in patients with chemotherapy only (HR 5.558, 95% CI 1.335-23.135, P = 0.018) and chemoradiotherapy (HR 3.057, 95% CI 1.270-7.539, P = 0.013). CONCLUSIONS: Comprehensive management of CVD comorbidities is of vital importance for the long-term prognosis of SCLC patients.
Assuntos
Doenças Cardiovasculares , Quimiorradioterapia , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Masculino , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Idoso , Prognóstico , Comorbidade , Fatores de Risco , Modelos de Riscos Proporcionais , Estudos Retrospectivos , China/epidemiologia , Derrame Pericárdico/etiologia , Derrame Pericárdico/epidemiologia , Derrame Pericárdico/mortalidade , Adulto , Taxa de SobrevidaRESUMO
OBJECTIVE: Guidelines for treatment of non-small cell lung cancer identify patients with tumors ≤2 cm and pure carcinoma in situ histology as candidates for sublobar resection. Although the merits of lobectomy, sublobar resection, and lymphoid (LN) sampling, have been investigated in early-stage non-small cell lung cancer, evaluation of these modalities in patients with IS disease can provide meaningful clinical information. This study aims to compare these operations and their relationship with regional LN sampling in this population. METHODS: The National Cancer Database was used to identify patients diagnosed with non-small cell lung cancer clinical Tis N0 M0 with a tumor size ≤2 cm from 2004 to 2017. The χ2 tests were used to examine subgroup differences by type of surgery. Kaplan-Meier method and Cox proportional hazard model were used to compare overall survival. RESULTS: Of 707 patients, 56.7% (401 out of 707) underwent sublobar resection and 43.3% (306 out of 707) underwent lobectomy. There was no difference in 5-year overall survival in the sublobar resection group (85.1%) compared with the lobectomy group (88.9%; P = .341). Multivariable survival analyses showed no difference in overall survival (hazard ratio, 1.044; P = .885) in the treatment groups. LN sampling was performed in 50.9% of patients treated with sublobar resection. In this group, LN sampling was not associated with improved survival (84.9% vs 85.0%; P = .741). CONCLUSIONS: We observed no difference in overall survival between sublobar resection and lobectomy in patients with cTis N0 M0 non-small cell lung cancer with tumors ≤2 cm. Sublobar resection may be an appropriate surgical option for this population. LN sampling was not associated with improved survival in patients treated with sublobar resection.
Assuntos
Carcinoma in Situ , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Pneumonectomia/métodos , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma in Situ/etiologia , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVES: Stereotactic body radiation therapy (SBRT) is increasingly used to treat non-small cell lung cancer. The purpose of this study is to analyze relationships between facility SBRT utilization and surgical patient selection and survival after surgery. METHODS: Data on patients with TI/T2N0M0 lesions and treatment facility characteristics were abstracted from the National Cancer Database, 2008 to 2017. Facilities were stratified using an SBRT/surgery ratio previously associated with short-term survival benefit for patients treated surgically, and by a previously identified surgical volume threshold. Multiple regression analyses, Cox proportional-hazard regressions, and Kaplan-Meier log rank test were employed. RESULTS: In total, 182,610 patients were included. Proportion of high SBRT:surgery ratio (≥17%) facilities increased from 118 (11.5%) to 558 (48.4%) over the study period. Patients undergoing surgery at high-SBRT facilities had comparable comorbidity scores and tumor sizes to those at low-SBRT facilities, and nonclinically significant differences in age, race, and insurance status. Among low-volume surgical facilities, treatment at a high SBRT-using facility was associated with decreased 30-day mortality (1.8% vs 1.4%, P < .001) and 90-day mortality (3.3% vs 2.6%, P < .001). At high-volume surgical facilities, no difference was observed. At 5 years, a survival advantage was identified for patients undergoing resection at facilities with high surgical volumes (hazard ratio, 0.91; confidence interval, 0.90-0.93 P < .001) but not at high SBRT-utilizing facilities. CONCLUSIONS: Differences in short-term survival following resection at facilities with high-SBRT utilization may be attributable to low surgical volume facilities. Patients treated at high volume surgical facilities do not demonstrate differences in short-term or long-term survival based on facility SBRT utilization.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Radiocirurgia/efeitos adversos , Seleção de Pacientes , Carcinoma de Pequenas Células do Pulmão/patologia , Estadiamento de Neoplasias , Resultado do Tratamento , Estudos RetrospectivosRESUMO
PURPOSE: Small cell lung cancer (SCLC) is a heterogeneous malignancy with genetic and phenotypic disparity. However, the association between intratumor heterogeneity (ITH) and immunological features as well as the impact of ITH on prognosis has never been explored in SCLC. Hence, we investigated the relationship between ITH and their immunological features and explored the effect of ITH on overall survival (OS) in patients with SCLC. METHODS: Programmed cell death-ligand 1 (PD-L1), CD8+ cell infiltration was calculated through immunohistochemical staining and tumor mutational burden (TMB), tumor neoantigen burden (TNB), and ITH levels via whole-exome sequencing (WES). RESULTS: Significant correlation was not found in ITH versus TMB, ITH versus TNB (P = 0.1821, P = 0.0612). No significant variation in ITH was found between negative PD-L1 SCLC patients and positive PD-L1 ones (P = 0.0610 for TPS, P = 0.6347 for CPS). Interestingly, we demonstrated the negative correlation between CD8+ T cell infiltration and ITH (P = 0.0220). More importantly, significant OS benefit was detected in ITH-low SCLC patients in comparison with ITH-high ones (P = 0.0049). ITH was an independent prognostic factor on OS with clinicopathological variables adjusted (HR, 2.044; 95% CI 1.190-3.512; P = 0.010). We also demonstrated significantly different driver genes and CNV between ITH-low and ITH-high SCLC. CONCLUSION: Our work pointed the negative association of ITH with CD8+ T cell infiltration and suggested ITH as a potential predictor of OS in SCLC, putting forward a direction for more precise and individualized therapeutic strategies for SCLC.