Risk factors for local and regional recurrence in patients with resected N0–N1 non-small-cell lung cancer, with implications for patient selection for adjuvant radiation therapy

Guerra, Julio; Gomez, Daniel R.; Lin, Sheng‐Hao; Levy, L.B.; Zhuang, Yan; Komaki, Ritsuko; Jaen, J.; Vaporciyan, Ara A.; Swisher, Stephen G.; Cox, James D.; Liao, Zhongxing; Rice, David C.

doi:10.1093/annonc/mds274

Cited by 60 publications

(18 citation statements)

References 26 publications

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“… 5 However, results of some studies have challenged the role of VPI as a prognostic parameter in NSCLCs. 6 – 8 Since the existence of VPI upgrades T stage of primary tumor from T1 to T2 in TNM staging system and may determine whether adjuvant chemotherapy is required, it is necessary to confirm the prognostic significance and identify the subset of patients with VPI who might benefit from adjuvant chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

The predictive and prognostic values of factors associated with visceral pleural involvement in resected lung adenocarcinomas

Zhang¹,

Chen

Lu³

et al. 2016

OTT

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BackgroundThe predictive and prognostic impact of factors associated with visceral pleural invasion (VPI) on survival and recurrence in patients with resected lung adenocarcinomas is not clearly defined.Patients and methodsA total of 505 consecutive patients with stage Ia–IIIa lung adenocarcinomas treated with radical resection were included. The predominant growth pattern was classified according to the new classification system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. The correlations of VPI with clinical and pathologic parameters were analyzed.ResultsThe incidence of VPI was significantly lower in lepidic predominant group (15.5% vs 4.5%, P<0.001) and higher in solid and micropapillary predominant group (28.6% vs 17.6%, P=0.004 and 14.7% vs 4.2%, P<0.001, respectively). VPI correlated with higher risk in regional postoperative recurrence (hazard ratio, 2.341; 95% confidence interval, 1.564–3.504) and distant recurrence (hazard ratio, 2.193; 95% confidence interval, 1.665–2.89) in surgically resected lung adenocarcinomas. However, when growth patterns of adenocarcinoma were lumped into multivariate analysis, VPI was not a significant independent predictive factor for survival (P=0.854 for overall survival [OS] and P=0.575 for disease-free survival [DFS]) and recurrence (P=0.38 for regional recurrence and P=0.089 for distant recurrence). Of the 95 patients with stage Ib, those who received adjuvant chemotherapy had longer DFS and OS than the patients who received no chemotherapy after surgery. However, these differences in DFS and OS did not reach statistical significance (P=0.063 for DFS, P=0.85 for OS).ConclusionVPI was associated with solid and micropapillary histology. In addition, stage Ib patients with solid histologic subtype tumor showed longer DFS and OS, highlighting a potential benefit in this subgroup of patients and necessitating the need for larger clinical trials.

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Section: Introductionmentioning

confidence: 99%

The predictive and prognostic values of factors associated with visceral pleural involvement in resected lung adenocarcinomas

Zhang¹,

Chen

Lu³

et al. 2016

OTT

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“…Lung cancer is the firstcause of malignancy related mortality worldwide, with more than one million cases diagnosed yearly[ 22 ]. NSCLC, accounting for 80% of all lung cancers, includes squamous carcinoma, adenocarcinoma and large cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effects between mTOR Complex 1/2 and Glycolysis Inhibitors in Non-Small-Cell Lung Carcinoma Cells

et al. 2015

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Cancer metabolism has greatly interested researchers. Mammalian target of rapamycin (mTOR) is dysregulated in a variety of cancers and considered to be an appealing therapeutic target. It has been proven that growth factor signal, mediated by mTOR complex 1 (mTORC1), drives cancer metabolism by regulating key enzymes in metabolic pathways. However, the role of mTORC2 in cancer metabolism has not been thoroughly investigated. In this study, by employing automated spectrophotometry, we found the level of glucose uptake was decreased in non-small-cell lung carcinoma (NSCLC) A549, PC-9 and SK-MES-1 cells treated with rapamycin or siRNA against Raptor, indicating that the inhibition of mTORC1 attenuated glycolytic metabolism in NSCLC cells. Moreover, the inhibition of AKT reduced glucose uptake in the cells as well, suggesting the involvement of AKT pathway in mTORC1 mediated glycolytic metabolism. Furthermore, our results showed a significant decrease in glucose uptake in rictor down-regulated NSCLC cells, implying a critical role of mTORC2 in NSCLC cell glycolysis. In addition, the experiments for MTT, ATP, and clonogenic assays demonstrated a reduction in cell proliferation, cell viability, and colony forming ability in mTOR inhibiting NSCLC cells. Interestingly, the combined application of mTORC1/2 inhibitors and glycolysis inhibitor not only suppressed the cell proliferation and colony formation, but also induced cell apoptosis, and such an effect of the combined application was stronger than that caused by mTORC1/2 inhibitors alone. In conclusion, this study reports a novel effect of mTORC2 on NSCLC cell metabolism, and reveals the synergistic effects between mTOR complex 1/2 and glycolysis inhibitors, suggesting that the combined application of mTORC1/2 and glycolysis inhibitors may be a new promising approach to treat NSCLC.

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“…Model A included five clinical variables—VPI, LVI, tumor size, tumor grade, and sub-lobar resection (segmentectomy or wedge resection)—and was fit by Cox proportional hazards regression. A comprehensive literature review revealed these five variables to be the most commonly associated with recurrence [5, 10–18]. Model B consisted of all variables in model A with the intent of evaluating the addition of up to five biomarkers—vascular endothelial growth factor-C (VEGF-C) and microRNA (miRNA) precursors miR-1, miR-486, miR-499, and miR-30D.…”

Section: Methodsmentioning

confidence: 99%

“…We aimed to develop and validate a prediction model for recurrence as a first step toward designing a risk-stratified approach for the selective use of adjuvant therapy and surveillance imaging. We were unable to develop a model that reliably performed better than chance in predicting recurrence despite using five previously identified clinical risk factors for recurrence [5, 10–18]. The addition of novel biomarkers associated with poor survival [23, 25] did not improve the model’s ability to predict recurrence.…”

Section: Commentmentioning

confidence: 99%

Challenges in Predicting Recurrence After Resection of Node-Negative Non-Small Cell Lung Cancer

Thornblade

Mulligan

Odem‐Davis

et al. 2018

The Annals of Thoracic Surgery

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Risk factors for local and regional recurrence in patients with resected N0–N1 non-small-cell lung cancer, with implications for patient selection for adjuvant radiation therapy

Abstract: Patients with N0-N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.

Cited by 60 publications

References 26 publications

The predictive and prognostic values of factors associated with visceral pleural involvement in resected lung adenocarcinomas

The predictive and prognostic values of factors associated with visceral pleural involvement in resected lung adenocarcinomas

Synergistic Effects between mTOR Complex 1/2 and Glycolysis Inhibitors in Non-Small-Cell Lung Carcinoma Cells

Challenges in Predicting Recurrence After Resection of Node-Negative Non-Small Cell Lung Cancer

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