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Kazuhiko Shien
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MA20 - Thymic Tumors: From Molecular to Clinical Results and New Challenges in Other Rare Thoracic Tumors (ID 149)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 1
- Now Available
- Moderators:Kazuya Kondo, Edith Michelle Marom
- Coordinates: 9/10/2019, 11:30 - 13:00, San Francisco (2009)
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MA20.11 - Surgical Treatment for Metastatic Lung Tumors from Sarcomas of Soft Tissue and Bone (Now Available) (ID 2391)
11:30 - 13:00 | Author(s): Kazuhiko Shien
- Abstract
- Presentation
Background
Sarcoma is one of the refractory malignant tumors and often develops pulmonary metastasis. The purpose of this study was to evaluate the impact of surgical resection for metastatic lung tumors from sarcomas of soft tissue and bone retrospectively.
Method
Between 2006 and 2015, we had a total of 158 patients with metastatic lung tumors from soft-tissue and bone sarcomas who underwent pulmonary metastasectomy for the first time. In total, 265 surgical procedures were performed in Okayama University Hospital in this period. We analyzed the age, sex, site of primary lesion, histology, extent of primary tumors at the initial diagnosis, extent of pulmonary metastases at the first pulmonary metastasectomy, presence or absence of local recurrence and/or extrapulmonary metastases with or before pulmonary metastases, operative procedures, size of the largest lesions resected, maximum number of the resected tumors, postoperative complications, and the prognosis at the end of 2018.
Result
Average number of resected tumors per intervention was 4.0 (range 1-19). These sarcoma patients consisted of 36 males and 122 females, and their average age was 53.7 years (range 14-88 years). Leiomyosarcoma was the most common histological subtype (n = 92, 58.2%) and uterus was the most common location of the primary disease (n = 71, 44.9%). Operative procedures were composed of 202 partial resections, 35 segmentectomies with or without partial resections, 26 lobectomies with or without partial resections, 1 pneumonectomy, and 1 basal segmental auto-transplantation after pneumonectomy. The postoperative complications were limited, showing that pulmonary metastasectomies for sarcomas are acceptable. Overall 3-year survival after the first pulmonary metastasectomy was 50.6%. In univariate analysis, the survival was significantly better for the group with disease-free interval of more than 2 years from the date of the initial treatment for primary disease until the date of diagnosis for the first pulmonary metastasis, the one who underwent pulmonary resections three times or more, and the one in which size of the largest resected lesion was 20 mm or less. Those factors significant in univariate analysis were all significant in multivariate analysis.
Conclusion
Surgical resections for metastatic lung tumors from sarcomas of soft tissue and bone were performed without major complications, indicating the acceptable feasibility. If disease-free interval is more than 2 years and the size of the largest resected lesion is less than 20 mm, patients may maximally benefit from pulmonary resection. In order to increase the opportunities of pulmonary resections, we should preserve the lung parenchyma as much as possible when performing pulmonary metatstasectomy, resulting in the better survival.
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P1.03 - Biology (ID 161)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.03-16 - Anti-Tumor Effect of Pan-RAF Inhibitor in NSCLC Cells Harboring BRAF Mutation (Now Available) (ID 1206)
09:45 - 18:00 | Author(s): Kazuhiko Shien
- Abstract
Background
BRAF mutation occurs in 0.5-3% of lung adenocarcinoma and acts as an oncogenic driver. Dabrafenib (BRAF inhibitor) combined with trametinib (MEK inhibitor) has shown substantial antitumor effect in patients with non-small-cell lung cancer (NSCLC) harboring BRAF V600E mutation. However, in patients with NSCLC harboring BRAF non-V600E mutation, there are few reports of effective targeted therapy. LY3009120, a newly discovered pan-RAF inhibitor, showed strong anti-tumor effect in BRAF-mutant cancers, such as melanoma, colorectal and pancreatic cancers in preclinical studies. In this study, we evaluated the anti-tumor effect of LY3009120 in BRAF-mutant NSCLC cells.
Method
We examined the sensitivity of LY3009120 against normal bronchial cells BEAS-2B which ectopically overexpressing wild-type or mutant BRAF. Human cDNAs encoding full-length BRAF (wild-type and its variants V600E and G469V) were inserted into the pIDT-SMART (C-TSC) vector, pCMViRTSC. In addition, we treated four BRAF-mutant NSCLC cell lines, one BRAF-mutant colorectal cancer cell line, and one KRAS-mutant cell line with LY3009120. The type of BRAF mutation consisted of V600E, L597V, G469A, and G466V. We determined cell proliferation by MTS assay and calculated the IC50 values. We also performed Western blotting to investigate downstream signaling pathways.
Result
BEAS-2B cells ectopically overexpressing wild-type BRAF or mutants (V600E and G469V) showed constitutive auto phosphorylation of BRAF and activation of downstream signaling by Western blotting. The IC50 values in BRAF mutant cell lines ranged from 9.4nM to 1,193nM, which suggests strong anti-tumor effect of LY3009120. This effect was observed regardless of the type of BRAF mutation, including non-V600E mutation. On the other hand, LY3009120 did not show anti-tumor effect in KRAS-mutant cell (IC50 value, 6,948nM). LY3009120 suppressed the phosphorylation of downstream MEK and ERK activation in BRAF-mutant cell lines by Western blotting.
Conclusion
LY3009120 showed strong anti-tumor effect in NSCLC cells harboring BRAF mutation regardless of the type of mutation, suggesting that LY3009120 can be a promising therapeutic option in the treatment of NSCLC harboring BRAF mutation.
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P2.18 - Treatment of Locoregional Disease - NSCLC (ID 191)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.18-12 - Prognostic Nutrition Index Affects Prognosis of Trimodality Therapy for Locally Advanced Lung Cancer with High T Factor (Now Available) (ID 1644)
10:15 - 18:15 | Author(s): Kazuhiko Shien
- Abstract
Background
Pretreatment nutritional status critically affects the clinical outcomes. Induction chemoradiotherapy (iCRT) followed by surgery (trimodality therapy) is a high-invasive treatment option for patients with locally advanced non-small cell lung cancer (LA-NSCLC). LA-NSCLC is a heterogeneous disease. Direct invasion into the surrounding structures easily promotes the invasion-related symptoms which inpair quality of life, but lymph node metastasis rarely causes its related symptoms until the bulky metastatic lymph nodes invade the surrounding structures. These differences of disease extent are expected to affect not only clinical outcome of treatment but also nutritional condition before initiation of treatment. While the prognostic nutritional index (PNI) is known to be correlated with the clinical outcomes after surgery in patients with early NSCLC, the significance of the PNI in LA-NSCLC patients undergoing trimodality therapy has not yet been well examined. In this study, we investigated the clinical impact of PNI in the LA-NSCLC patients who underwent iCRT followed by surgery considering the heterogeneity of disease extent.
Method
We enrolled 127 patients who received trimodality therapy at our institution between 1999 and 2016. The PNI was examined at all three time-points in the patients: before iCRT, before surgery, and after surgery.
Result
Fifty-five and 72 patients were diagnosed as clinical T1/2 (cT1/2) and cT3/4 diseases, respectively, and, 42 and 85 patients were cN0/1 and cN2/3, respectively. The PNI significantly decreased as the treatment progressed among all 127 patients. Patients with cT3/4 disease showed significantly lower PNI values before and after surgery than those with cT1/2 disease. By contrast, the PNIs were equivalent at all time-points between patients with cN2/3 and cN0/1 disease. We performed receiver-operating characteristic curve analysis to determine the cutoff the pre-iCRT PNI for overall survival (OS) in all (n = 127), cT3/4 (n = 72) and cN2/3 patients. The ROC curve analyses indicated that a significant cutoff was identified only in cT3/4 patients. Univariate and multivariate analyses revealed that high pre-iCRT PNI values were significantly correlated with better survival in cT3/4 patients. By contrast, the prognostic impact of pre-iCRT PNI values could not be observed in cN2/3 patients
Conclusion
The nutritional status deteriorates as the treatment progresses during trimodality therapy. Intensive perioperative nutritional intervention is required especially for cT3/4 LA-NSCLC patients receiving trimodality therapy.
