Development and validation of a prognostic nomogram for patients with laryngeal cancer with synchronous or metachronous lung cancer.

BACKGROUND: The objective of this study was to examine the independent prognostic factors of laryngeal cancer with synchronous or metachronous lung cancer (LCSMLC), and to generate and verify a clinical prediction model. METHODS: In this study, laryngeal cancer alone and LCSMLC were defined using the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors of patients with LCSMLC were analyzed through univariate and multivariate logistic regression analysis. Independent prognostic factors were selected by Cox regression analyses, on the basis of which a nomogram was constructed using R code. Kaplan-Meier survival analyses were applied to test the application of a risk stratification system. Finally, we conducted a comparison of the American Joint Committee on Cancer (AJCC) staging system of laryngeal cancer with the new model of nomogram and risk stratification. For further validation of the nomogram, data from patients at two Chinese independent institutions were also analyzed. RESULTS: According to the eligibility criteria, 32 429 patients with laryngeal cancer alone and 641 patients with LCSMLC from the SEER database (the training cohort) and additional 61 patients from two Chinese independent institutions (the external validation cohort) were included for final analyses. Compared with patients with laryngeal cancer who did not have synchronous or metachronous lung cancer, age, sex, race, primary site of laryngeal cancer, grade, and stage were risk factors for LCSMLC, while marriage, surgery, radiation therapy, and chemotherapy are not their risk factors. Age, two cancers' interval, pathological type, stage, surgery, radiation, primary lung site, and primary throat site were independent prognostic predictors of LCSMLC. The risk stratification system of high-, medium-, and low-risk groups significantly distinguished the prognosis in different patients with LCSMLC, regardless of the training cohort or the validation cohort. Compared with the 6th AJCC TNM stage of laryngeal cancer, the new model of nomogram and risk stratification showed an improved net benefit. CONCLUSIONS: Age, sex, race, primary site of laryngeal cancer, grade, and stage were risk factors for LCSMLC. An individualized clinical prognostic predictive model by nomogram was generated and validated, which showed superior prediction ability for LCSMLC.

Best Supportive Care Versus Whole-Brain Irradiation, Chemotherapy Alone, or WBRT Plus Chemotherapy in Patients With Brain Metastases From Small-Cell Lung Cancer: A Case-Controlled Analysis.

BACKGROUND: WBRT and systemic chemotherapy are the mainstay treatments for small-cell lung cancer (SCLC) brain metastases (BM). However, current recommendations are mainly based on evidence from retrospective analyses. A recent randomized trial found no benefits from WBRT compared with best supportive care (BSC) in patients with more than three BM from non-small-cell lung cancer (NSCLC). Herein, we aimed to evaluate the roles of WBRT and chemotherapy further in the management of BM from SCLC. MATERIALS AND METHODS: There were 698 patients with BM from SCLC included. Of these, 580 received anti cancer treatment (Group 1), including 178 who received WBRT only (Group 1a), 129 who received chemotherapy only (Group 1b), and 273 who received WBRT plus chemotherapy (Group 1c). The other 118 received BSC (Group 2). Propensity score matching (PSM) analysis was used to compare Group 2 with each of the other groups. RESULTS: After PSM, compared with Group 2 (n = 118), patients in Group 1 (n = 440) had a prolonged overall survival (OS) in both univariate and multivariate tests, with a median survival time of 10 months (95% CI = 9-11) in Group 1 and 3.5 months (95% CI = 2-7) in Group 2 (p < 0.001). In subgroup analyses, patients who received WBRT plus chemotherapy were more likely to benefit from treatment (p < 0.001). Chemotherapy alone or WBRT alone did not show survival benefits. CONCLUSION: WBRT plus chemotherapy improved OS in patients with BM from SCLC as compared to BSC. Chemotherapy alone and WBRT alone did not show survival benefits. This retrospective study suggests that SCLC patients with BM who receive WBRT combined with chemotherapy have a better outcome than those receiving BSC alone.

Validation of a novel prognostic index: BMS-Score for patients with brain metastases of small cell lung cancer.

BACKGROUND: A new disease-specific prognostic score (Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer termed BMS-Score) was published to clarify the prognosis of patients with brain metastasis (BM) of small cell lung cancer (SCLC) treated with whole brain radiotherapy (WBRT). The purpose of the present study was to validate the prognostic value of the newly proposed BMS-Score through comparison with three other previously published prognostic indices. METHODS: In total, 451 patients with BM of SCLC treated with WBRT at the Shanxi Province Cancer Hospital from January 2010 to December 2019 were included. The clinical characteristics of all patients were recorded and follow-up was through April 2020. Overall survival (OS) was calculated by Kaplan-Meier analysis, and univariate and multivariate analyses were used to calculate the prognostic cofactors. The concordance index (C-index) was used to assess the prognostic value of the following four prognostic systems: recursive partitioning analysis (RPA), diagnosis-specific graded prognostic assessment (DS-GPA), basic score for brain metastases (BSBM), and the newly proposed BMS-Score. RESULTS: The independent factors affecting the prognosis of SCLC patients with BM included the Karnofsky performance score (KPS), number of brain metastases, extracranial metastases (ECM) state, and whether treatment had been received before BM. RPA, BSBM, DS-GPA, and BMS-Score log-rank test P values were all less than 0.001 among each group (P<0.001). The C-indices of the four groups were 0.554, 0.584, 0.588, and 0.643, respectively. CONCLUSIONS: The four prognostic scoring systems exhibited medium predictive value for SCLC. The BMS-Score had the best applicability compared with the other three prognosis indices.

The Clinical Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Brain Metastases from Non-Small Cell Lung Cancer-Harboring EGFR Mutations.

PURPOSE: Several studies have explored the correlation between the neutrophil-to-lymphocyte ratio (NLR) and the prognosis of patients with lung cancer. However, little is known about the correlation between the pretreatment NLR and the prognosis of patients with brain metastases from non-small cell lung cancer (NSCLC)-harboring mutations in the epidermal growth factor receptor (EGFR) gene. We sought to evaluate the predictive values in brain metastasis from lung adenocarcinoma with EGFR mutations. METHODS: We retrospectively examined 133 patients with brain metastases (BMs) from lung adenocarcinoma with EGFR mutations. NLR was calculated using N/L, where N and L, respectively, refer to peripheral blood neutrophil (N) and lymphocyte (L) counts. The cut-off value of NLR was assessed by the area under the curve (AUC). The Log rank test and Cox proportional hazard model were used to confirm the impact of NLR and other variables on survival. RESULTS: An NLR value equal to or less than 2.99 was associated with prolonged survival in this cohort of patients in both variable and multivariable analysis. CONCLUSION: We concluded that NLR is an independent prognostic factor in BMs from lung adenocarcinoma with EGFR mutations. This could serve as a useful prognostic biomarker and could be incorporated in the clinical prognostic index specific to patients with BMs.

Prognostic role of the systemic immune-inflammation index in brain metastases from lung adenocarcinoma with different EGFR mutations.

The prognostic value of the systemic immune-inflammation index (SII) has been shown in various types of cancers. We aimed to evaluate the predictive values in brain metastases from lung adenocarcinoma with status of EGFR mutations. We, retrospectively, examined 310 patients with brain metastases from lung adenocarcinoma with status of EGFR mutations. SII was calculated using P * N/L, where P, N, and L, respectively refer to peripheral blood lymphocyte, neutrophil, and platelet counts. The cut-off value of SII was assessed by area under the curve (AUC). The log-rank test and Cox proportional hazard model were used to confirm the impact of SII and other variables on survival. The SII value ≤ 1218.81 was associated with prolonged survival in patients with brain metastases from lung adenocarcinoma in both variable and multivariable analysis In patients with EGFR mutations, the SII had statistical effect on OS only in invariable test. While, for patients with wild-type EGFR, SII achieved statistically significant differences both in variable and multivariable analyses. SII is an independent prognostic factor in brain metastases from lung adenocarcinoma. SII may have varying prognostic effects on patients with and without EGFR mutations and is a promising variable for the future prognostic systems.

Applicability of graded prognostic assessment of lung cancer using molecular markers to lung adenocarcinoma patients with brain metastases.

Several scoring systems are available to estimate prognosis and assist in selecting treatment methods for non-small cell lung cancer (NSCLC) patients with brain metastasis, including recursive partitioning analysis (RPA), basic score for brain metastases (BS-BM), and diagnosis-specific graded prognostic assessment (DS-GPA). Lung-molGPA is an update of the DS-GPA that incorporates EGFR and/or ALK mutation status. The present study tested the applicability of these four indexes in 361 lung adenocarcinoma patients with brain metastasis. Potential predictive factors in our independent multivariate analysis included patient age, Karnofsky performance status, EGFR and ALK mutation status, and use of targeted therapy. In the log-rank test, all four systems predicted overall survival (OS) (P<0.001). Harrell's C indexes were 0.732, 0.724, 0.729, and 0.747 for RPA, BS-BM, DS-GPA, and Lung-molGPA, respectively. Our results confirmed that the Lung-molGPA index was useful for estimating OS in our patient cohort, and appeared to provide the most accurate predictions. However, the independent prognostic factors identified in our study were not entirely in agreement with the Lung-molGPA factors. In an era of targeted therapy, Lung-molGPA must be further updated to incorporate more specific prognostic factors based on additional patient data.

Prognostic model for brain metastases from lung adenocarcinoma identified with epidermal growth factor receptor mutation status.

BACKGROUND: Several indices have been developed to predict survival of brain metastases (BM) based on prognostic factors. However, such models were designed for general brain metastases from different kinds of cancers, and prognostic factors vary between cancers and histological subtypes. Recently, studies have indicated that epidermal growth factor receptor (EGFR) mutation status may be a potential prognostic biological factor in BM from lung adenocarcinoma. Thus, we sought to define the role of EGFR mutation in prognoses and introduce a prognostic model specific for BM from lung adenocarcinoma. METHODS: Data of 256 patients with BM from lung adenocarcinoma identified with EGFR mutations were collected. Independent prognostic factors were confirmed using a Cox regression model. The new prognostic model was developed based on the results of multivariable analyses. The score of each factor was calculated by six-month survival. Prognostic groups were divided into low, medium, and high risk based on the total scores. The prediction ability of the new model was compared to the three existing models. RESULTS: EGFR mutation and Karnofsky performance status were independent prognostic factors and were thus integrated into the new prognostic model. The new model was superior to the three other scoring systems regarding the prediction of three, six, and 12-month survival by pairwise comparison of the area under the curve. CONCLUSION: Our proposed prognostic model specific for BM from lung adenocarcinoma incorporating EGFR mutation status was valid in predicting patient survival. Further verification is warranted, with prospective testing using large sample sizes.

Assessment of prognostic scores of brain metastases from lung adenocarcinoma with EGFR mutations.

The aim of this study was to analyze prognostic factors and evaluate the value of four prognostic scores including RPA, DS-GPA BS-BM, GGS for the EGFR mutant BM patients from lung adenocarcinoma treated with EGFR-TKI. Data of NSCLC were retrospectively reviewed from August 2010 to June 2015 using the medical database of Shanxi Provincial Cancer Hospital. Patients with BM from lung adenocarcinoma with mutant EGFR treated by EGFR-TKI or a combination of EGFR-TKI and WBRT were included. Potential prognostic factors were statistically examined. The C-index of each prognostic score was calculated. A total of 1063 BM patients with lung adenocarcinoma that had been identified with EGFR mutations were reviewed. A total of 104 patients that had been diagnosed with BM were confirmed to have mutant EGFR in primary tumors. These patients received treatment with EGFR-TKI or EGFR-TKI with WBRT to BM. The potential predictive factors in multivariable analysis included KPS (70 vs.70-80 vs. 90-100) and number of brain metastatic lesions. In the log-rank test, the indexes of RPA, DS-GPA BS-BM, and GGS were all significant predictors of OS. The C-indexes of each prognostic score were 0.79, 0.76, 0.77, and 0.74 in DS-GPA, RPA, GGS, and BS-BM, respectively. The indexes of RPA, DS-GPA BS-BM, GGS were applicable for asessing survival stratification in brain metastases from lung adenocarcinoma with presented EGFR mutations in our independent population. The DS-GPA appears to be the best predictive value. However, all four of the indexes could not evaluate the exact independent prognostic factors in multivariable analysis. A prognostic index specific for this group of patients was needed for targeted lung cancer therapy.

Correlation between status of epidermal growth factor receptor mutation and distant metastases of lung adenocarcinoma upon initial diagnosis based on 1063 patients in China.

The study aimed to explore the correlations between status of epidermal growth factor receptor (EGFR) mutations and distant metastases. A total of 1063 patients with lung adenocarcinoma indentified with status of EGFR mutations from August 2010 to May 2015 at Shanxi Cancer Hospital were enrolled. 456 patients were confirmed with EGFR mutations. The associations among EGFR mutations, clinical factors, and distant metastases at initial diagnosis were evaluated. Patients harboring EGFR mutation were more likely to be female (P < 0.001), with no smoking history (P < 0.001), brain metastases (P = 0.029), and higher ECOG performance scores (P = 0.025). The correlation between EGFR mutation status and distant metastases showed statistical significance both in univariate (P = 0.022) and in multivariate analysis (OR 1.573, 95 % CI 1.202-2.059, P = 0.001) especially in brain metastases (OR 1.675, 95 % CI 1.132-2.479, P = 0.010) and lung metastases (OR 1.571, 59 % CI 1.101-2.243 P = 0.013). Furthermore, the 19del mutations showed associations with brain metastases (OR 1.586, 95 % CI 1.028-2.447, P = 0.037), and lung metastases (OR 1.587, 95 % CI 1.065-2.346, P = 0.023). The exon 21 point mutations showed statistically significant differences in liver metastases (OR 1.987, 95 % CI 1.094-3.067, P = 0.024). In conclusion, the EGFR mutations in lung adenocarcinoma patients were independently correlated with distant metastases. Subgroup analyses showed that patients harboring 19del mutations presented different distant metastases compared with those harboring 21 point mutaions.

Exon 19 deletion of epidermal growth factor receptor is associated with prolonged survival in brain metastases from non-small-cell lung cancer.

Brain metastasis (BM) is a poor prognostic factor for non-small-cell lung cancer (NSCLC). Recent studies have shown that oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were effective for BM from NSCLC with EGFR mutation. However, the relationship between EGFR mutations and prognosis of NSCLC BM patients remains to be determined. In this study, we investigated the impact of EGFR mutation status on the survival of BM patients from NSCLC. One hundred six patients with BM from NSCLC were retrospectively reviewed. Thirty-three subjects (24.3 %) were confirmed to have an exon 19 deletion, while another 33 had an exon 21 point mutation (L858R) (24.3 %). Log-rank test and Cox proportional hazards model were used to analyze the impact of variables on survival. The median survival of NSCLC with BM was 8 months. Log-rank test analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG-PS) at BM (p < 0.0001), control of primary tumor (p = 0.005), pathology (p = 0.01), EGFR mutations (p = 0.045), and 19 exon deletion (p = 0.007) were associated with a longer survival. In a Cox proportional hazards model, EGFR exon 19 deletion (p = 0.034), control of primary tumor (p = 0.024), and ECOG PS at BM (p = 0.006) were found to be independent prognostic factors. Moreover, there were prognostic differences between groups according to Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classification system (p < 0.0001). Exon 19 deletion is an independent prognostic factor in BM from NSCLC. It should be integrated into the prognostic scoring classification system for NSCLC.