Predicting Postrecurrence Survival Among Completely Resected Nonsmall-Cell Lung Cancer Patients

doi:10.1016/j.athoracsur.2005.09.020

The Annals of Thoracic Surgery

Volume 81, Issue 3, March 2006, Pages 1021-1027

https://doi.org/10.1016/j.athoracsur.2005.09.020 Get rights and content

Background

Survival after recurrence subsequent to complete resection of nonsmall-cell lung cancer (NSCLC) has been considered a multifactorial process dependent on demographic, clinical, biological, and treatment characteristics. This study sought to quantify the prognostic effects of these characteristics on postrecurrence survival.

Methods

Three hundred ninety NSCLC patients who underwent complete resection and subsequently had recurrent cancer were studied. The associations between characteristics of both the initial and recurrent disease with postrecurrence survival were evaluated by Cox proportional hazards models. A multivariable Cox model determined those factors most strongly associated with postrecurrence survival . A simple algorithm based on this model facilitates estimating risk of postrecurrence mortality, as quantified by risk score points.

Results

The factors most strongly associated with postrecurrence survival were performance status at recurrence (3 or 4, 4.2 points; 2, 2.8 points; and 1, 1.5 points), symptoms at recurrence (3.6 points), liver recurrence (2.3 points), initial lung cancer stage IIB or worse (1.8 points), and multiple recurrences (1.0 points). Based on these factors, patients were stratified as low risk (4.0 or fewer total points), moderate-low risk (4.1 to 6.1 points), moderate-high risk (6.1 to 8.0 points), and high risk (more than 8.0 points), with 12-month survival of 75%, 51%, 25%, and 9%, respectively. Postrecurrence survival was significantly different across groups (p < 0.01).

Conclusions

The proposed prediction instrument offers clinicians a succinct tool for rapidly evaluating mortality risk after recurrence. The characteristics comprising this instrument can be easily ascertained and measured, making it of potential clinical value.

Section snippets

Patients and Methods

The Mayo Clinic Epidemiology and Genetics of Lung Cancer Research Program has enrolled and prospectively followed patients either diagnosed with or treated for lung cancer at Mayo Clinic, Rochester, Minnesota, since its inception in 1997. The Mayo Foundation Institutional Review Board approved this study before any patient enrollment. Between January 1, 1997, and December 31, 2001, 4,673 patients (4,155 NSCLC, 518 small-cell lung cancer) have been enrolled. Procedures for identifying and

Results

Among 1,073 NSCLC patients who underwent a complete resection with curative intent, 445 (41.5%) were identified as having recurrent disease during the study follow-up period. Fifty-five patients who had a recurrence had to be excluded from this analysis because of a lack of information on date of recurrence, anatomical site, or treatment for recurrence. A comparison between these 55 patients and the remaining 390 patients with complete data on lung cancer recurrence showed that age, state of

Comment

Our investigation of an extensive collection of potential risk factors for postrecurrence mortality after a complete resection for NSCLC included nearly twice as many subjects as previous studies considering both local and distant recurrences, permitting more rigorous investigation of risk factors related to both the initial lung cancer and subsequent recurrence. Our prior analysis [23] identified several characteristics, including therapies for both the initial lung and recurrent cancers,

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Patients with early NSCLC (eNSCLC) who experience recurrence are associated with worse survival outcomes, but the economic burden of recurrence is not well characterized. This study evaluated the incremental health care resource utilization and costs of recurrence in Medicare patients with resected eNSCLC.
This retrospective observational study used Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims. Eligible patients were 65 years and older with newly diagnosed NSCLC stages IB to IIIA (American Joint Committee on Cancer Staging Manual, seventh edition) and surgery between January 2010 and December 2017. Continuous enrollment criteria were applied to ensure appropriate data capture. Per patient per month (PPPM) health care resource utilization and all-cause direct costs were compared for patients with versus without recurrence, which was identified from claims data using diagnosis, procedure, or drug codes. Patients were matched (1:1) using exact matching on cancer stage and treatment, and propensity score matching on other characteristics.
In total, 2035 (44%) out of 4595 patients had evidence of recurrence. After matching, 1494 patients were included in each cohort. Patients with recurrence had a significantly higher number of inpatient visits (+0.25 PPPM), outpatient visits (+1.10 PPPM), physician services (+3.70 PPPM), and emergency department (ED) visits (+0.25 PPPM; all p < 0.001). The average follow-up PPPM cost in the recurrence cohort was U.S. dollars $7437 and $1118 in the no-recurrence cohort, resulting in a difference of $6319 PPPM (p < 0.001) with inpatient costs as the largest contributor.
On the basis of a real-world population, the recurrence among patients with resected eNSCLC is associated with increased health care resource utilization and costs.
Identification of hub genes, modules and biological pathways associated with lung adenocarcinoma: A system biology approach
2022, Gene Reports
Lung adenocarcinoma (LUAD) is the most common non-small cell lung cancer with an alarming trend within non-smokers at younger ages. This study is designed to identify mechanisms of LUAD compared to normal lung tissues using systems biology approaches. Four GSE datasets (GSE75037, GSE63459, GSE32863 and GSE10072) were selected from the Gene Expression Omnibus database. Data processing and meta-analysis were performed using the R statistical programming language. The common and unique DEGs between stages of LUAD and normal lung tissues were initiated by the Venny tool. Common genes were then analyzed in a STRING database to obtain protein-protein interaction. STRING output was analyzed by MCODE and CytoHubba applications of Cytoscape to identify modules of co-expression and hub genes, respectively. The correlation between hub genes and survival of LUAD patients was explored using UALCAN. The hub genes from the meta-analysis were confirmed using an independent, comprehensive LUAD RNA-sequencing dataset collected from The Cancer Genome Atlas (TCGA). The shared upregulated and downregulated DEGs among LUAD stages were 22 and 140 genes, respectively, when compared to normal lung tissues. Unique genes for each stage were also identified. The hub genes were PECAM1, TEK, CDH5, VWF and ANGPT1. An inverse correlation was found between the expression levels of ANGPT1 gene and overall survival of LUAD patients (p-value = 0.02). Most of the top cluster genes were enriched for Gα(s) signalling events, GPCR ligand binding, class B/2 (Secretin family receptors), platelet activation, signalling and aggregation in the main three co-expression clusters. Most of the shared genes were enriched in the biological pathway of hemostasis. TCGA analysis showed that hub genes derived from common genes were found statistically significant throughout all stages. In conclusion, unique upregulated and downregulated DEGs at each stage were identified with FERMT1 and SIX1 as specific early-stage diagnostic biomarkers for stage IB and IIB. 5 hub genes were observed, including PECAM1, TEK, CDH5, vWF and ANGPT1 which might be crucial for the onset and progression of LUAD. Interestingly, ANGPT1 can be considered as a potential and valuable prognostic marker in LUAD patients.
A novel epithelial-mesenchymal transition-related gene signature for prognosis prediction in patients with lung adenocarcinoma
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Traditional pathological diagnoses and clinical methods are insufficient to accurately predict the prognosis of lung adenocarcinoma (LUAD). Epithelial-mesenchymal transition (EMT) process is closely related to tumor cell migration. However, the prognostic value of EMT-related genes in LUAD is still unclear. In this study, we collected bulk RNA-sequencing (RNA-seq) and microarray data of LUAD patients from public databases and identified different expressed EMT-related genes in tumor and normal tissues. Then, we used the least absolute shrinkage and selection operator Cox regression model to develop a multigene signature in the cancer genome atlas (TCGA) cohort and validated the model in the OncoSG (Singapore Oncology Data Portal) cohort as well as other datasets. Finally, we constructed a 12-gene signature to divide LUAD patients into high-risk and low-risk groups of overall survival (OS), which has a better stability and accuracy in predicating the OS of patients compared with some other published signatures of LUAD. In addition, evaluation of the risk model using the time-related receiver operating characteristic (ROC) curve confirmed the predictive ability of the model. Functional analysis showed that these genes are related to immunity. CD8 T cell and CD4 T cell types were significantly negatively correlated with the risk score in the analysis of immune infiltration. In general, our model provides useful information that may help clinicians better predict the prognosis of LUAD patients and provides potential targets for immunotherapy of LUAD.
Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study
2022, JTO Clinical and Research Reports
Citation Excerpt :
In early and locally advanced (stages I–III) NSCLC, which comprises approximately one-third of diagnosed NSCLCs, surgical resection is recommended as an option by clinical guidelines.4-7 Nevertheless, many patients with resected NSCLC experience recurrence (13.2%–41.5% depending on disease stage and length of follow-up).8-13 Postrecurrence survival after surgery is poor (median overall survival [OS]: ∼26 mo), which presents a clinical unmet need.8,11
The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment.
This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc.
Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6–111.4) months, median OS and DFS were 103.3 (95% CI: 101.7–104.9) and 67.4 (95% CI: 49.7–85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3–73.6) and 52.9% (95% CI: 48.2–57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07–1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages.
EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.
Lung cancer recurrence and mortality outcomes over a 10-year period using a multidisciplinary team approach
2020, Cancer Epidemiology
Longitudinal data are limited regarding the impact of a multidisciplinary team (MDT) approach on patient outcomes among those diagnosed with lung cancer. The purpose of this study is to 1) compare 1- and 3-year recurrence and mortality rates among patients receiving a MDT vs. standard model of care; and 2) assess trends in these proportions over a 10-year period.
This investigation included 2044 lung cancer cases reported to the Stony Brook Cancer Registry between 2006 and 2015. Patients were stratified into 2 groups, those participating in Stony Brook’s Lung Cancer Evaluation Center’s (LCEC) MDT Program (n = 1179) and those receiving a standard model of care (n = 865). 1- and 3-year stage-stratified recurrence and mortality rates are reported. Logistic regression analyses are performed and linear by linear associations are used to assess trends over time.
A higher proportion of patients in the MDT program (LCEC) remained disease-free at 1-year compared those receiving standard care (80.0 % vs 62.3 %, p < 0.01). There were no significant changes in mortality over the 10-year observation period in either group, however the rates were significantly lower among LCEC vs non-LCEC cases after adjusting for possible confounders (OR = 0.68 (0.51,0.90) at 1-year; OR = 0.50 (0.36, 0.70) at 3-years). Recurrence was also lower at 3-years in the MDT group (OR = 0.51 (0.32, 0.79)).
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2019, Lung Cancer
Citation Excerpt :
The total number of patients who experienced disease recurrence was 31 (27%). As advanced disease stage is a known risk factor for recurrence in resected NSCLC [50], as expected, recurrence rates in this study were higher among patients with stage II-IIIA (33%) versus stage I disease (23%). At the median timepoint for the last blood sample collection (37 months), 30 out of 31 (97%) cases of disease recurrence had occurred (Fig. 1A and B).
The biomarkers cytokeratin 19 fragment (CYFRA 21-1) and human epididymis protein 4 (HE4) are useful in the diagnosis, prognosis, and monitoring of non-small cell lung cancer (NSCLC), but their combination has not been investigated yet. The objective of this analysis was to evaluate the ability of CYFRA 21-1 and HE4 to predict recurrence as part of follow-up monitoring in patients with adenocarcinoma (ADC) of the lung.
Serum samples were collected from patients with stage I-IIIA ADC preoperatively and during follow-up at 3, 6, 12, 18, and 24 months and then every 6–12 months up to 5 years post-R0 resection. Samples were analyzed for CYFRA 21-1 and HE4 via electrochemiluminescence immunoassay. All cases of disease recurrence were verified by imaging. The diagnostic performance of CYFRA 21-1, HE4, and their combination to predict recurrence was assessed by Receiver Operating Characteristic (ROC) and corresponding area under the curve (AUC).
115 patients with ADC were included (N = 612 biomarker measurements); median age was 63 years; most had stage I–II disease (n = 97; 84.3%). All patients underwent surgical resection; 44 patients (38%) also received adjuvant chemotherapy and 16 (14%) received radiation therapy. At the median timepoint for the last blood sample collection (37 months), 31 patients (27%) had experienced recurrence. Both CYFRA 21-1 and HE4 were able to detect recurrence (AUC and 95% confidence interval [CI]): 75.9% (66.0–85.8%) and 75.4% (65.9–84.8%), respectively, but this increased with the combination (78.8% [69.0–88.6%]). At a sensitivity of 80%, the respective specificities (95% CI) for CYFRA 21-1, HE4, and the combination were 57.1% (53.0–61.2%), 57.1% (53.0–61.2%), and 69.7% (65.8–73.4%).
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Original articleGeneral thoracicPredicting Postrecurrence Survival Among Completely Resected Nonsmall-Cell Lung Cancer Patients

Background

Methods

Results

Conclusions

Section snippets

Patients and Methods

Results

Comment

J Thorac Cardiovasc Surg

Chest

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

Ann Thorac Surg

Lung Cancer

Thorac Cardiovasc Surg

Lung Cancer

Ann Thorac Surg

Chest

Eur J Cancer

Chest

J Pain Sympton Manage

Eur J Cancer

J Clin Epidemiol

Disease recurrence after resection for stage I lung cancer

Eur J Cardiothorac Surg

Original article
General thoracic
Predicting Postrecurrence Survival Among Completely Resected Nonsmall-Cell Lung Cancer Patients