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Prognostic study for survival outcome following the treatment of second primary lung cancer in patients with previously resected non-small cell lung cancer.

ABSTRACT: BACKGROUND:Patients who have previously undergone surgical resection of initial primary lung cancer (IPLC) are at high risk of developing second primary lung cancer (SPLC). There are still no standard treatments for SPLC. This study aimed to identify the prognostic factors and compare survival between the different SPLC treatment groups. METHODS:SPLC patients in the Surveillance, Epidemiology, and End Results (SEER) database between 2007 and 2016 were retrospectively reviewed. Prognostic factors for SPLC were identified, using the least absolute shrinkage and selection operator (LASSO) regression and univariate Cox analysis to select variables for multivariate Cox analysis. Kaplan-Meier method plus log-rank test and restricted mean survival time (RMST) were used to compare survival outcome. RESULTS:A total of 665 SPLC patients were finally enrolled into the study. Multivariate Cox regression analysis revealed that male vs. female (HR = 1.82, 95% CI: 1.29-2.59, P = 0.001), tumor size of SPLC ?1 cm vs. <1 cm (HR = 1.80, 96% CI: 1.07-3.02, P = 1.028), IPLC characteristics of squamous cell carcinoma vs. adenocarcinoma (HR = 1.89, 95% CI: 1.17-3.04, P = 0.009), clinical stage II vs. stage I (HR = 2.60, 95% CI: 1.08-6.27, P = 0.033), and T2 stage vs. T1 stage (HR = 1.68, 95% CI: 1.04-2.72, P = 0.034) indicated worse survival. SPLC patients demonstrated a five-year survival rate of 68.6% and a five-year RMST of 49.4 months. The choice of surgical procedure (wedge resection, segmentectomy and lobectomy) for both IPLC and SPLC had no significant effect on prognosis (P?>?0.05). Patients that received radiotherapy for SPLC also demonstrated similar survival when compared with those that underwent surgery (P?>?0.05). CONCLUSIONS:Radiotherapy and sublobar resection can be considered reasonable alternative treatments for SPLC, especially when patients are unable to tolerate lobectomy.

SUBMITTER: Wu Y

PROVIDER: S-EPMC7529572 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Prognostic study for survival outcome following the treatment of second primary lung cancer in patients with previously resected non-small cell lung cancer.

Wu Yijun Y Han Chang C Chong Yuming Y Liu Jianghao J Gong Liang L Wang Zhile Z Liang Naixin N

Thoracic cancer 20200826 10

<h4>Background</h4>Patients who have previously undergone surgical resection of initial primary lung cancer (IPLC) are at high risk of developing second primary lung cancer (SPLC). There are still no standard treatments for SPLC. This study aimed to identify the prognostic factors and compare survival between the different SPLC treatment groups.<h4>Methods</h4>SPLC patients in the Surveillance, Epidemiology, and End Results (SEER) database between 2007 and 2016 were retrospectively reviewed. Pro ...[more]

PMID: 32851789

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Project description:BackgroundAlthough early-stage non-small-cell lung cancer (NSCLC) is considered a potentially curable disease following complete resection, patients have a wide spectrum of survival according to stage (IB, II, IIIA). Within each stage, gene expression profiles can identify patients with a higher risk of recurrence. We hypothesized that altered mRNA expression in nine genes could help to predict disease outcome: excision repair cross-complementing 1 (ERCC1), myeloid zinc finger 1 (MZF1) and Twist1 (which regulate N-cadherin expression), ribonucleotide reductase subunit M1 (RRM1), thioredoxin-1 (TRX1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T cells (NFAT), BRCA1, and the human homolog of yeast budding uninhibited by benzimidazole (BubR1).Methodology and principal findingsWe performed real-time quantitative polymerase chain reaction (RT-QPCR) in frozen lung cancer tissue specimens from 126 chemonaive NSCLC patients who had undergone surgical resection and evaluated the association between gene expression levels and survival. For validation, we used paraffin-embedded specimens from 58 other NSCLC patients. A strong inter-gene correlation was observed between expression levels of all genes except NFAT. A Cox proportional hazards model indicated that along with disease stage, BRCA1 mRNA expression significantly correlated with overall survival (hazard ratio [HR], 1.98 [95% confidence interval (CI), 1.11-6]; P = 0.02). In the independent cohort of 58 patients, BRCA1 mRNA expression also significantly correlated with survival (HR, 2.4 [95%CI, 1.01-5.92]; P = 0.04).ConclusionsOverexpression of BRCA1 mRNA was strongly associated with poor survival in NSCLC patients, and the validation of this finding in an independent data set further strengthened this association. Since BRCA1 mRNA expression has previously been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 mRNA expression may provide additional information for customizing adjuvant antimicrotubule-based chemotherapy, especially in stage IB, where the role of adjuvant chemotherapy has not been clearly demonstrated.

Project description:BackgroundCure and long-term survival for non-small cell lung cancer (NSCLC) remains hard to achieve. Cellular senescence, an emerging hallmark of cancer, is considered as an endogenous tumor suppressor mechanism. However, senescent cancer cells can paradoxically affect the surrounding tumor microenvironment (TME), ultimately leading to cancer relapse and metastasis. As such, the role of cellular senescence in cancer is highly controversial.MethodsIn 155 formalin-fixed paraffin-embedded (FFPE) samples from surgically resected NSCLC patients with pathological tumor-node-metastasis (pTNM) stages I-IV (8th edition), cellular senescence was assessed using a combination of four immunohistochemical senescence markers, i.e., lipofuscin, p16INK4a, p21WAF1/Cip1 and Ki67, and correlated to clinicopathological parameters and outcomes, including overall survival (OS) and disease-free survival (DFS).ResultsA tumoral senescence signature (SS) was present in 48 out of 155 NSCLC patients, but did not correlate to any clinicopathological parameter, except for p53 mutation status. In a histologically homogenous patient cohort of 100 patients who fulfilled the following criteria: (I) one type of histology, i.e., adenocarcinoma, (II) without known epidermal growth factor receptor (EGFR) mutation, (III) curative (R0) resection and (IV) no neoadjuvant systemic therapy or radiotherapy, the median OS and DFS for patients with a tumoral SS (n=30, 30.0%) compared to patients without a tumoral SS (n=70, 70.0%) was 53 versus 141 months (P=0.005) and 45 versus 55 months (P=0.25), respectively. In multiple Cox proportional hazards (Cox PH) model analysis correcting for age, pTNM stage I-III and adjuvant therapy, a tumoral SS remained a significant prognostic factor for OS (HR =2.03; P=0.014).ConclusionsThe presence of a tumoral SS particularly based on high p16INK4a expression significantly affects OS in NSCLC adenocarcinoma. In this light, adjuvant senolytic therapy could be an interesting strategy for NSCLC patients harboring a tumoral SS, ultimately to improve survival of these patients.

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Prognostic study for survival outcome following the treatment of second primary lung cancer in patients with previously resected non-small cell lung cancer.

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Prognostic study for survival outcome following the treatment of second primary lung cancer in patients with previously resected non-small cell lung cancer.

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