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Zhihao Zheng
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EP1.08 - Oligometastatic NSCLC (ID 198)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Oligometastatic NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.08-05 - Local Non-Salvage Radiotherapy for Synchronous Oligometastatic NSCLC: A Multicenter, Randomized, Controlled, Phase 2 Study (Now Available) (ID 573)
08:00 - 18:00 | Author(s): Zhihao Zheng
- Abstract
Background
Previous studies had suggested that aggressive thoracical treatment, such as surgery, might lead to higher local control rate and better long-term survival in oligometastatic NSCLC. Radiotherapy (RT) is also an effective and less invasive local treatment. Therefore, we assessed the role of addition of aggressive thoracical RT to first-line systemic therapy in patients with synchronous oligometastatic NSCLC.
Method
Stage IV patients with measurable primary tumor and distant metastases number ≤5, histologically or cytologically confirmed NSCLC and ECOG PS≤2 were included. All enrolled patients had not previously experienced local or systemic antitumor treatment, including surgery (biopsy is allowed), first line chemotherapy, targeted therapy or immunotherapy. Other inclusion criteria included adequate organ function and life expectancy of >3 months. Our study randomized patients at 1:1 ratio to receive systemic therapy plus radiotherapy(RT+) or systemic therapy alone(RT-). First-line regimens recommended by NCCN guidelines are allowed for systemic therapy, including standard platinum-based doublet chemotherapy, targeted therapy, antiangiogenic therapy and immunotherapy. Three-dimensional conformal radiotherapy(3D-CRT) or Intensity modulated radiotherapy(IMRT) to primary thoracic foci or remediable oligometastatic focus should be given no later than disease progression. Randomization was stratified by histological type (squamous cell carcinoma vs. adenocarcinoma), first-line systemic therapy (targeted therapy vs. non-targeted therapy), intracranial metastasis (yes vs. no), number of metastases (1 vs. 2-5) and local stage (I/II vs. III). Primary endpoint of this study is progression-free survival(PFS) based on RECIST v. 1.1 criteria. Secondary endpoint are local tumor control; oligometastatic foci control; thoracic progression-free survival(TPFS); overall survival(OS); toxicity and compliance. The study has 80% power to detect a greater effect of RT+ group in PFS at a 2-sided alpha level of 0.05. Assuming a 10% drop-out rate, randomization of 148 patients was planned. The trial opened in China in November 2017. To date, 14 patients have been randomized and 2 sites in China have activated the trial. Support: 81572279, 2016J004, LC2016PY016, 2018CR033. Clinical trial information: NCT03119519.
Result
Section not applicable
Conclusion
Section not applicable
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-59 - The Role of Radiation Dose-Dependent Lipid Metabolism Reprogramming on Radiation Survival/Resistance in Lung Cancer Cells (ID 2051)
10:15 - 18:15 | Author(s): Zhihao Zheng
- Abstract
Background
Radiotherapy plays a more and more important role in the management of lung cancer. However, radioresistance still limits the long-term control of tumors. Exploration of the dynamic changes of metabolic reprogramming in surviving/resistant lung cancer cells exposed to increased doses of radiation is helpful to elucidate the metabolic mechanism of radiation resistance in lung cancer cells, to develop new targets for the clinical intervention and the early detection of radiation resistance.
Method
Lung cancer cells A549, H520 and H460 were treated in vitro with fractionated radiation (2 Gy) to a cumulative total dose of 40Gy, 60Gy or 80Gy. Cellular radiation sensitivity was verified by colony survival assay and comet experiments. Cell proliferation was determined by EdU assay. Transcriptome sequencing and metabolomic analysis were performed to identify differentially expressed genes and metabolites in radiation-resistant cells and their parental cells. Oil Red O staining was used to detect lipid droplet content. RT-PCR and WB were used to detect the expression of genes related to lipid metabolism.
Result
Lung cancer cell sublines that had been exposed to 20, 30 or 40 fractions of 2Gy had a significant increase in radioresistance as compared with their parental cells. Furthermore, this radioresistance of cells increased with the increase of previous radiation dose exposure. We found that lipid droplet deposition and the expression of lipid metabolism genes, such as fatty acid oxidation-related genes and glycerol metabolism-related genes, showed an increasing trend with previous radiation dose in surviving/resistant lung cancer cells exposed to radiation. Metabolomic analysis revealed that lipid metabolites such as glycerol and oxaloacetic acid also increased significantly. Inhibition of carnitine palmitoyltransferase 1A (CPT1A) by Etomoxir, a fatty acid oxidation inhibitor, significantly enhanced the radiosensitivity and decreased the DNA repair ability of various surviving/resistant lung cancer cells exposed to radiation.
Conclusion
The surviving/resistant lung cancer cells generated by sequential irradiation provide models for future investigations of the dose-dependent mechanisms of radioresistance in a preclinical setting. Radiation dose-dependent lipid metabolism reprogramming may contribute to radiation survival/resistance in lung cancer cells. Support: 81572279, 2016J004, LC2016PY016, 2018CR033.
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P2.08 - Oligometastatic NSCLC (ID 172)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Oligometastatic NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.08-06 - Development and Validation of a 18F-FDG PET/CT-Based Radiomics Model for Prognosis Prediction in Synchronous Oligometastatic NSCLC (ID 1818)
10:15 - 18:15 | Author(s): Zhihao Zheng
- Abstract
Background
Oligometastatic non-small cell lung cancer (NSCLC) exists high heterogeneity with distinct outcome, and there is a lack of available biomarkers for patient stratification. In this study, we identified a positron emission tomography (PET)/computed tomography(CT)-based radiomics signature capable of predicting overall survival (OS) in patients with synchronous oligometastatic NSCLC.
Method
A primary cohort consisted of 46 patients with synchronous oligometastatic NSCLC (≤5 metastases) between January 2012 and December 2017. Clinicopathologic data was acquired from medical records and database. A total of 20648 radiomic features were extracted from pretreatment CT and PET images, which were generated from the same PET/CT scanner. A radiomics signature was built by using the least absolute shrinkage and selection operator (LASSO) regression model. Multivariate Cox regression analysis was performed to establish the predictive model. A prospective internal validation cohort contained 14 patients from January 2018 to December 2018. The performance was evaluated with Harrell’ concordance index (C-index).
Result
7 radiomics features were selected to build the radiomics signature. Smoking status (P=0.01) was the only independent clinicopathologic risk factor for overall survival prediction. Multivariate analysis indicated that the radiomics signature (P=0.007) was an independent prognostic factor, with a C-index of 0.810 and 0.900 for the primary and validation cohort.
Conclusion
This study developed a radiomics model for predicting OS in synchronous oligometastatic NSCLC, which may serve as a predictive tool to identify individualized treatment strategy. Further external validation of the model are required. Support: 81572279, 2016J004, LC2016PY016, 2018CR033.
