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Both the presence of a micropapillary component and the micropapillary predominant subtype predict poor prognosis after lung adenocarcinoma resection: a meta-analysis.

ABSTRACT: OBJECTIVE:It has been confirmed that the micropapillary (MP) pattern is a poor prognostic factor after resection of lung adenocarcinoma (ADC), but the proportion of the MP component as a prognostic criterion is still controversial. Hence, a meta-analysis was performed to evaluate whether the presence of an MP component has equal prognostic power as the MP predominant subtype. METHODS:Literature retrieval was performed in the MEDLINE, EMBASE, and Cochrane databases until December 23, 2019. Eligible studies were selected based on the inclusion and exclusion criteria. The included studies were divided into two subgroups, the MP component subgroup and the MP predominant subgroup, according to the proportion of the MP pattern to analyse the effect of this pattern on disease-free survival (DFS) and overall survival (OS). The hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study. Review Manager 5.3 was used for statistical analyses. RESULTS:Finally, 10 studies, including a total of 4934 lung ADC patients, were included in this meta-analysis. Our results indicated a significantly worse pooled DFS (HR 1.62, 95% CI 1.20-2.21) and OS (HR 1.53, 95% CI 1.19-1.96) in the subgroup of MP predominant subtype patients. The pooled DFS (HR 1.80, 95% CI 1.45-2.85) and OS (HR 2.26, 95% CI 1.46-3.52) were also poor in the subgroup of patients with the presence of an MP component. CONCLUSIONS:Both the presence of an MP component and the MP predominant subtype are related to poor DFS and OS after lung ADC resection and represent adverse prognostic factor for lung ADC patients. However, there are some limitations in this meta-analysis, and quantitative stratification based on the proportion of the MP component is needed to explore its effect on prognosis of lung ADC patients in the future.

SUBMITTER: Wang W

PROVIDER: S-EPMC7325156 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Both the presence of a micropapillary component and the micropapillary predominant subtype predict poor prognosis after lung adenocarcinoma resection: a meta-analysis.

Wang Wei W Hu Zaoxiu Z Zhao Jie J Huang Yunchao Y Rao Sunyin S Yang Jichen J Xiao Shouyong S Cao Run R Ye Lianhua L

Journal of cardiothoracic surgery 20200629 1

<h4>Objective</h4>It has been confirmed that the micropapillary (MP) pattern is a poor prognostic factor after resection of lung adenocarcinoma (ADC), but the proportion of the MP component as a prognostic criterion is still controversial. Hence, a meta-analysis was performed to evaluate whether the presence of an MP component has equal prognostic power as the MP predominant subtype.<h4>Methods</h4>Literature retrieval was performed in the MEDLINE, EMBASE, and Cochrane databases until December 2 ...[more]

PMID: 32600473

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Project description:BackgroundWe investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA.MethodsWe enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP-, respectively), and between the group with an S/MP proportion of ?5% (S/MP5) and the S/MP-.ResultsThe S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP- group (P?<?0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups (P?<?0.001, all comparisons for S/MP+ vs. S/MP-; P???0.01, all comparisons for S/MP5 vs. S/MP-). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer-related death than the S/MP- group(P?<?0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA.ConclusionsThe presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed.Key pointsSignificant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma.What this study addsOur results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma.

Project description:BackgroundWe sought to analyze the prognostic significance of the new International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) lung adenocarcinoma (ADC) classification for patients undergoing resection for small (≤2cm) lung ADC and to investigate whether histologic subtyping can predict recurrence after limited resection (LR) vs lobectomy (LO).MethodsComprehensive histologic subtyping was performed according to the IASLC/ATS/ERS classification on all consecutive patients who underwent LR or LO for small lung ADC between 1995 and 2009 at Memorial Sloan-Kettering Cancer Center. Clinical characteristics and pathologic data were retrospectively evaluated for 734 consecutive patients (LR: 258; LO: 476). Cumulative incidence of recurrence (CIR) was calculated using competing risks analysis and compared across groups using Grey's test. All statistical tests were two-sided.ResultsApplication of IASLC/ATS/ERS lung ADC histologic subtyping to predict recurrence demonstrates that, in the LR group but not in the LO group, micropapillary (MIP) component of 5% or greater was associated with an increased risk of recurrence, compared with MIP component of less than 5% (LR: 5-year CIR = 34.2%, 95% confidence interval [CI] = 23.5% to 49.7% vs 5-year CIR = 12.4%, 95% CI = 6.9% to 22.1%, P < .001; LO: 5-year CIR = 19.1%, 95% CI = 12.0% to 30.5% vs 15-year CIR = 12.9%, 95% CI = 7.6% to 21.9%, P = .13). In the LR group, among patients with tumors with an MIP component of 5% or greater, most recurrences (63.4%) were locoregional; MIP component of 5% or greater was statistically significantly associated with increased risk of local recurrence when the surgical margin was less than 1cm (5-year CIR = 32.0%, 95% CI = 18.6% to 46.0% for MIP ≥ 5% vs 5-year CIR = 7.6%, 95% CI = 2.3% to 15.6% for MIP < 5%; P = .007) but not when surgical margin was 1cm or greater (5-year CIR = 13.0%, 95% CI = 4.1% to 22.1% for MIP ≥ 5% vs 5-year CIR = 3.4%, 95% CI = 0% to 7.7% for MIP < 5%; P = .10).ConclusionsApplication of the IASLC/ATS/ERS classification identifies the presence of an MIP component of 5% or greater as independently associated with the risk of recurrence in patients treated with LR.

Project description:BackgroundThe efficacy of sublobar resection and selective lymph node dissection is gradually being accepted by thoracic surgeons for patients within early-stage non-small cell lung cancer (NSCLC). Nevertheless, there are still some NSCLC patients develop lymphatic metastasis at clinical T1 stage. Lung adenocarcinoma with a micropapillary (MP) component poses a higher risk of lymph node metastasis and recurrence even when the MP component is not predominant. Our study aimed to explore the genetic features and occult lymph node metastasis (OLNM) risk factors in patients with a non-predominant micropapillary component (NP-MPC) in a large of patient's cohort with surgically resected lung adenocarcinoma.MethodsBetween January 2019 and December 2021, 6418 patients who underwent complete resection for primary lung adenocarcinoma at the Qilu Hospital of Shandong University. In our study, 442 patients diagnosed with lung adenocarcinoma with NP-MPC with a tumor size ≤3 cm were included. Genetic alterations were analyzed using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Abnormal protein expression of gene mutations was validated using immunohistochemistry. A nomogram risk model based on clinicopathological parameters was developed to predict OLNM. This model was invalidated using the calibration plot and concordance index.ResultsIn our retrospective cohort, the incidence rate of the micropapillary component was 11.17%, and OLNM was observed in 20.13% of the patients in our study. ARMS-PCR suggested that EGFR exon 19 del was the most frequent alteration in NP-MCP patients compared with other gene mutations (frequency: 21.2%, P<0.001). Patients harboring exon 19 del showed significantly higher risk of OLNM (P< 0.001). A nomogram was developed based on five risk parameters, which showed good calibration and reliable discrimination ability (C-index = 0.84) for evaluating OLNM risk.ConclusionsIntense expression of EGFR exon 19 del characterizes lung adenocarcinoma in patients with NP-MCP and it's a potential risk factor for OLNM. We firstly established a nomogram based on age, CYFRA21-1 level, tumor size, micropapillary and solid composition, that was effective in predicting OLNM among NP-MCP of lung adenocarcinoma measuring ≤ 3 cm.

Project description:BackgroundMicropapillary adenocarcinoma is one of the most aggressive histologic subtypes of lung adenocarcinoma (LADC), and even a minor proportion of micropapillary component (MPC) within the LADC could contribute to poor prognosis. Comprehensive analysis of genetic and immunological features of LADC with different percentages of MPC would help better understand cancer biology of this LADC subtype and direct future treatments.MethodsWe performed next-generation sequencing (NGS) for a discovery cohort of 43 LADC patients whose tumors were micro-dissected to separate MPC and non-MPC lesions and a reference cohort of 113 LADC patients. MPC-enriched genetic alterations that were detected in the discovery cohort were then confirmed using a validation cohort of 183 LADC patients. Immunological staining was also conducted on the MPC-containing samples in the discovery cohort.ResultsTumors with a higher percentage of MPC tended to harbor more tumor mutation burdens (TMBs) and chromosome instability (CIN). Some rare genetic events may serve as the genetic landscape to drive micropapillary tumor progression. Specifically, alterations in transcription termination factor 1 (TTF1), brain-specific angiogenesis inhibitor 3 (BAI3), mammalian target of rapamycin (MTOR), and cyclin-dependent kinase inhibitor 2A (CDKN2A) were cross-validated to be enriched in MPC-contained LADC. Additionally, tumors with a higher percentage of MPC were associated with a higher percentage of CD4+, CD8+, and PD-L1+ staining, and some genetic changes that were enriched in MPC, including MET amplification and MTOR mutation, were correlated with increased PD-L1 expression.ConclusionWe identified multiple novel MPC-enriched genetic changes that could help us understand the nature of this aggressive cancer subtype. High MPC tumors tended to have elevated levels of TMBs, T cell infiltration, and immunosuppression than low MPC tumors, implying the potential link between MPC content and sensitivity to immunotherapy.

Project description:ObjectiveWe aimed to investigate whether enhanced CT-based radiomics can predict micropapillary pattern (MPP) of lung invasive adenocarcinoma (IAC) in the pre-op phase and to develop an individual diagnostic predictive model for MPP in IAC.Methods170 patients who underwent complete resection for pathologically confirmed lung IAC were included in our study. Of these 121 were used as a training cohort and the other 49 as a test cohort. Clinical features and enhanced CT images were collected and assessed. Quantitative CT analysis was performed based on feature types including first order, shape, gray-level co-occurrence matrix-based, gray-level size zone matrix-based, gray-level run length matrix-based, gray-level dependence matrix-based, neighboring gray tone difference matrix-based features and transform types including Log, wavelet and local binary pattern. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to value the ability to identify the lung IAC with MPP using these characteristics.ResultsUsing quantitative CT analysis, one thousand three hundred and seventeen radiomics features were deciphered from R (https://www.r-project.org/). Then these radiomic features were decreased to 14 features after dimension reduction using the least absolute shrinkage and selection operator (LASSO) method in R. After correlation analysis, 5 key features were obtained and used as signatures for predicting MPP within IAC. The individualized prediction model which included age, smoking, family tumor history and radiomics signature had better identification (AUC=0.739) in comparison with the model consisting only of radiomics features (AUC=0.722). DeLong test showed that the difference in AUC between the two models was statistically significant (P<0.01). Compared with the simple radiomics model, the more comprehensive individual prediction model has better prediction performance.ConclusionThe use of radiomics approach is of great value in the diagnosis of tumors by non-invasive means. The individualized prediction model in the study, when incorporated with age, smoking and radiomics signature, had effective predictive performance of lung IAC with MPP lesions. The combination of imaging features and clinical features can provide additional diagnostic value to identify the micropapillary pattern in IAC and can affect clinical diagnosis and treatment.

Project description:ObjectivesThis study aimed to construct prediction models based on computerized tomography (CT) signs, histogram and morphology features for the diagnosis of micropapillary or solid (MIP/SOL) components of stage IA lung adenocarcinoma (LUAC) and to evaluate the models' performance.MethodsThis clinical retrospective study included image data of 376 patients with stage IA LUAC based on postoperative pathology, admitted to Putian First Hospital from January 2019 to June 2023. According to the presence of MIP/SOL components in postoperative pathology, patients were divided into MIP/SOL+ and MIP/SOL- groups. Cases with tumors ≤ 3 cm and ≤ 2 cm were separately analyzed. Each subgroup of patients was then randomly divided into a training set and a test set in a ratio of 7:3. The training set was used to build the prediction model, and the test set was used for internal validation.ResultsFor tumors ≤ 3 cm, ground-glass opacity (GGO) [odds ratio (OR) = 0.244; 95% confidence interval (CI): 0.103-0.569; p = 0.001], entropy (OR = 1.748; 95% CI: 1.213-2.577; p = 0.004), average CT value (OR = 1.002; 95% CI: 1.000-1.004; p = 0.002), and kurtosis (OR = 1.240; 95% CI: 1.023-1.513; p = 0.030) were independent predictors of MIP/SOL components of stage IA LUAC. The area under the ROC curve (AUC) of the nomogram prediction model for predicting MIP/SOL components was 0.816 (95% CI: 0.756-0.877) in the training set and 0.789 (95% CI: 0.689-0.889) in the test set. In contrast, for tumors ≤ 2 cm, kurtosis was no longer an independent predictor. The nomogram prediction model had an AUC of 0.811 (95% CI: 0.731-0.891) in the training set and 0.833 (95% CI: 0.733-0.932) in the test set.ConclusionFor tumors ≤ 3 cm and ≤ 2 cm, GGO, average CT value, and entropy were the same independent influencing factors in predicting MIP/SOL components of stage IA LUAC. The nomogram prediction models have potential diagnostic value for identifying MIP/SOL components of early-stage LUAC.

Project description:Background The histologic classification of lung adenocarcinoma (LUAD) was mainly divided into three pathological subtype groups: the low-grade predominant subtype group (lepidic), the intermediate-grade predominant subtype group (papillary and acinar), and the high-grade predominant subtype group (micropapillary and solid). Previous studies have focused on the prognostic impact of predominant subtypes of lung adenocarcinoma. In this investigation, we investigated the effect of the second predominant subtype on prognosis. Methods The data of LUAD postoperative patients were retrospectively collected. Exclusion criteria included cases in which the pathologic results revealed a single characteristic, the presence of invasive mucinous LUAD, or if the first predominant and the second predominant groups could not be distinguished. Categorical variables were compared with the two-tailed Pearson χ2 test and continuous variables with the Student’s t-test. Follow-up was conducted by telephone and other methods. Independent prognostic factors of the second major subtype were determined by the Kaplan-Meier method and log-rank test. The Cox proportional risk regression model was used to analyze the possible prognostic factors. Results Among 293 patients, the mean age was 61.9 years and 47.1% were male. The results revealed that when the predominant group was the low-grade group, the second predominant groups had no significant influence on overall survival (OS) (P=0.15) but significantly influenced disease free survival (DFS) (P=0.037). Subsequently, when the predominant group was the intermediate-grade group, the second predominant groups significantly influenced OS (P=0.024) but had no significant influence on DFS (P=0.3). Moreover, when the predominant group was the high-grade group, the second predominant groups significantly influenced OS (P=0.033) but had no significant influence on DFS (P=0.31). Conclusions The independent prognostic effect of the second predominant group was not identified for OS and DFS of lung adenocarcinoma. The effects of the second predominant subtype groups on OS and DFS were not evenly distributed among different predominant subtype groups, and the low-grade second predominant subtype exhibited some protective effects on the middle-grade predominant subtypes.

Dataset Information

Both the presence of a micropapillary component and the micropapillary predominant subtype predict poor prognosis after lung adenocarcinoma resection: a meta-analysis.

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Both the presence of a micropapillary component and the micropapillary predominant subtype predict poor prognosis after lung adenocarcinoma resection: a meta-analysis.

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