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MINI 33 - Radiotherapy and Complications (ID 164)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
MINI33.04 - Acute Radiation Pneumonitis in Lung Cancer Treated with Volumetric Modulated Arc Therapy (ID 2634)
18:30 - 20:00 | Author(s): Z. Wu
Thoracic radiotherapy plays an important role in the treatment of lung cancer. However, the safety of thoracic radiotherapy delivery is restricted to the risk of radiation pneumonitis(RP), which is the major dose limiting toxicity for patients undergoing thoracic radiotherapy. Few studies to date have assessed risk factors associated with the development of RP in lung cancer patients treated with volumetric modulated arc therapy (VMAT). This study aimed to report the RP incidence and clinical and dosimetric risk factors associated with RP in lung cancer patients treated with VMAT at a single institution.
In this retrospective study, lung cancer patients treated with VMAT from 2013 through 2015 were reviewed. RP was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version.4.0. Clinical factors and dosimetric parameters were evaluated using logistic multivariate regression for estimating the correlation with RP. The results were considered statistically significant when the p-value was<0.05.
Thoracic radiotherapy with VMAT was administered in 77 lung cancer patients. Of these patients, 58 were men and 19 were women, with a median age of 60 years (range 22-84 years); 25 patients received concurrent chemoradiotherapy, and the median radiation dose was 60Gy (range 45-64Gy). VMAT plans were performed with single arc in 9 patients, double in 55 patients, triple in 4 patients, and the mean (±SD) delivery time was 189.1s±42.0s. VMAT allowed us to respect most planning objectives on target volumes and organs at risk, for PTV V~95% ~= 96.8 ± 6.1%; for lung V~5~ = 41.3 ± 8.7%, V~10~ = 29.9 ± 7.1%, V~20~ = 20.9 ± 5.7%, mean dose=1150.9±277.6Gy. With regard to acute RP after thoracic radiotherapy, 10.4% were grade 1 (G1), 16.9% G2, 9.1% G3, 2.6% G5. The overall incidence rate of symptomatic RP (grade ≥ 2 by CTCAE) was 28.6% in the entire cohort. Based on the clinical data and dosimetric parameters analysis, factors predictive of symptomatic RP were lung volume receiving ≥10Gy (V~10~) [OR: 1.39, 95% CI 1.07–1.80, p=0.014], PS score[OR:5.44, 95% CI 1.29–23.08, p=0.021], concurrent chemotherapy[OR:3.85, 95% CI 1.07–13.86, p=0.039]and CRP changing level[OR:1.06, 95% CI 1.01–1.12, p=0.014].
VMAT, a novel technique, provides a viable option for the thoracic radiotherapy of lung cancer with acceptable toxicities. However, for patients with higher V~10~, poorer PS score, greater increasing level of CRP and undergoing concurrent chemotherapy, VAMT technique should be administrated with cautions. Several molecular biomarkers have been reported that correlated with the development of RP, which will be tested in our further analysis.
P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
P1.04-053 - Characterization of Invasive Cancer Cells and Potential Therapeutic Effect of Suberoylanilide Hydroxamic Acid on Human Lung Cancer Metastasis (ID 223)
09:30 - 17:00 | Author(s): Z. Wu
Lung cancer is a worldwide problem andthe leading cause of death among all malignancies. Despite tremendous progresses in diagnosis and treatment, the overall treatment outcomes for lung cancer patients remain poor, and metastatic lung cancer is responsible for more than ninety percent of lung cancer related deaths. However, the details for lung cancer invasion and thereafter metastasis remain unclear. In this study, we characterized the biological features of invasive human lung cancer cells, and investigated the potential therapeutic effects of Suberoylanilide Hydroxamic Acid (SAHA) on invasive cancer cell subpopulation.
Boyden-type cell invasion chambers were used for isolation of cancer cell subpopulations with high invasiveness (H-INV) and low invasiveness (L-INV) from human lung cancer H460 cells. The potential enrichment of stem cell-like cancer cells in H-INV cells and the resistances of H-INV cells to chemotherapy and radiation treatment were investigated. We also tested the effects of SAHA on the differentiation of cancer stem cell and its consequences on cancer cell invasion and the sensitivities to radio/chemotherapies in H-INV cells. Furthermore, microarray for message RNA was performed for identification of gene expression profiling for invasive cancer cells.
Comparing to L-INV cells, H-INV cells are with enrichments of stem cell-like cancer cells, with increased positive staining of putative stem cell markers such as CD24[low]/CD44[+] and OCT3/4, and more tumorigenic. H-INV cells are also more resistant to treatments of chemotherapeutic agents and ionizing radiation. Treatment with SAHA can induce differentiation of stem cell-like cell in H-INV cells, causing reduced cancer cell invasion and increased sensitivity to chemo/radiotherapy in cells. With mRNA microarray assay, we identified 453 genes differentially expressed in H-INV versus L-INV, and five of these genes have been further tested for their significances in paired primary and metastatic lung tumors.
Our study suggested putative roles of cancer stem cell in lung cancer invasion and migration. Study also showed that invasive lung cancer cells are resistant to most of first-line and second-line chemotherapeutic agents and radiotherapy, indicating novel therapeutic strategies are needed for the treatment of metastatic lung cancer. Of this setting, SAHA may serve as a chemotherapeutic agent for benefiting lung cancer patients. The candidate genes identified in this study may also have clinic impact as potential metastatic predictors for diagnosis and prognosis for human lung cancer.
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