Author of

• 25935

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  P1.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 947)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall

  • 26684

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    P1.15-17 - Risk Factors of Local Recurrence in EGFR-Mutant Stage III-pN2 Adenocarcinoma After Complete Resection: A Multi-Center Real-World Cohort Study (ID 12740)

    16:45 - 18:00  |  Author(s): Gang Wu
    • Abstract

    Background
    

    Postoperative radiotherapy (PORT) of complete resected stage IIIA non-small cell lung cancer with N2 nodal involvement remained contentious. Our previous study suggested low locoregional recurrences in epidermal growth factor receptor (EGFR) mutant patients. We sought to launch a multi-center large cohort study to evaluate the risk factors of locoregional recurrence in R0 resected EGFR mutant III-pN2 patients without PORT, producing evidence for the design of adjuvant regimens.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Three-hundred and fifty-nine consecutive patients with complete resected, pathological approved stage III-pN2 lung adenocarcinoma with sensitive EGFR mutation (exon 19 or exon 21) have been investigated. Patients were excluded if they received induction therapy (7.5%) or PORT (9.6%). Three hundred cases have been analyzed. Clinicopathologic characteristics, pretreatment work-ups, EGFR mutant status and patterns of failure were documented. Patients were sub-staged by the International Association for the Study of Lung Cancer (IASLC)/ the Union for International Cancer Control (UICC) 7^th classification on N2 disease. Risk factors of locoregional recurrence-free survival (LRFS) were evaluated by univariate and multivariate analyses.

    4c3880bb027f159e801041b1021e88e8 Result
    

    According to IASLC/UICC 7^th classification, there were 198 (66.0%) patients with unforeseen N2 (N2a), 36 (12.0%) with minimal/single station N2 (N2b), 41 (13.7%) with selectively centrally located N2 (N2c) and 25 (8.3%) with bulky and/or multilevel N2 (N2d). After surgery, 70 (23.3%) patients were treated with adjuvant tyrosine-kinase inhibitors (TKIs), while other 230 (76.7%) were free from adjuvant TKIs. With median follow-up of 28.5 (range：6-133) months, the 2-year LRFS, distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 88.3%, 65.3%, 57.7% and 89.7%. Ultimately, 15.7% (47/300) patients developed locoregional recurrences. Distant metastasis was the predominant failure pattern. Multivariate analysis indicated that N2d disease (HR: 2.65, p=0.030) and extranodal extension (HR: 3.48, p<0.001) were risk factors of LRFS.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    R0 resected stage III-pN2 NSCLC patients with sensitive EGFR mutation (exon 19 or exon 21) tended to present limited N2 disease and low locoregional recurrences. Patients without bulky N2, multilevel N2, and extranodal extension might be refrained from PORT. Further studies evaluating the optimal radiotherapy approach for completely resected N2-positive NSCLC are required for validation.

    6f8b794f3246b0c1e1780bb4d4d5dc53

• 25938

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  P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 26932

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    P2.01-127 - Efficacy of Endostar Combined with Whole Brain Radiotherapy in Patients with NSCLC Brain Metastases (ID 14231)

    16:45 - 18:00  |  Author(s): Gang Wu
    • Abstract
    • Slides

    Background
    

    Brain metastasis (BM) is the leading cause of poor prognosis, recurrence, and death in non-small-cell lung cancer (NSCLC) patients. The effectiveness of whole-brain radiotherapy is unsatisfactory. Endostar was reported as an anti-angiogenic agent, which could promote vascular normalization in tumor. This study is to investigate the influence of endostar combined with cranial radiation to cerebral blood flow, immune status and survival of the patients.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    28 NSCLC patients with multiple brain metastasis（more than four）were randomly divided into two groups. The experimental group (n = 14) received WBRT (30Gy/10F) combined with Endostar (15mg/m², 7days), and the control group (n=14) received WBRT (30Gy/10F) alone. Magnetic resonance perfusion imaging was carried out pre- and one month post-radiation to detect regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF) and mean transit time (MTT) of the contrast medium. The changes of blood T lymphocyte subpopulation, the cognitive function and overall healthy level were evaluated pre- and post- radiation every two months against the MMSE, MoCA and EORTC QLQ-C30 scales. Moreover, Tumor progression was established by certified oncologists based on whole brain MRI scan.

    4c3880bb027f159e801041b1021e88e8 Result
    

    In the endostar group, rCBV, rCBF and MTT had a 122%, 210% and 11% higher in the target lesion region one month post radiation, compared with baseline data, while in the control group, rCBV, rCBF and MTT had a 18%, 20% and 26% lower change. These results showed a significant improvement of the cerebral perfusion in the endostar group. The T lymphocyte subpopulation increased in the Endostar group, especially the CD8+ T lymphocyte with a significant difference compared with the control group(p=0.0233). At the same time, the intracranial PFS (iPFS) was 349 days vs. 287 days and the PFS was 229 days vs. undefined between the Endostar group vs. the control group, but neither with significant difference, may for the limit of sample size. After cranial radiation, the cognitive function, physical, role, social and emotional functions improved in the endostar group, while a small fluctuation in the control group.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Our study showed that endostar could promote vessel normalization and improve cerebral perfusion, and ameliorate the immune status, cognitive function and quality of life of the patients, which may also improve the survival of the patients.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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• 25955

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  P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

  • 27418

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    P3.01-62 - A New Method for Non-Invasive Prediction of Radiotherapy: SDH5 Depletion Enhances Radiosensitivity by Regulating P53 (ID 12871)

    12:00 - 13:30  |  Author(s): Gang Wu
    • Abstract

    Background
    

    Radiotherapy is an important and effective treatment for lung cancer. Some molecules can predict the effect of radiotherapy, but it is an invasive test that will cause trauma to patient. So the development of reliable non-invasive methods for predication of radiotherapy has become essential to guide therapy.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We initiated an analytical, observational, open, and retrospective study (ChiCTR1800014878) of 53 patients with stage III lung adenocarcinoma who were ready for radiotherapy. The performance status (PS) scores of the patients are all over 2. Blood and tumor tissue before treatment were collected to detect SDH5 concentration. We then evaluated the prognostic role of SDH5 expression in these patients. To further verify the effect of SDH5 on radiosensitivity, two mice models (orthotopic mice bearing lung cancer and SDH5 gene knock-out mice) were established and the internal mechanism between SDH5 and radiotherapy was explored.

    4c3880bb027f159e801041b1021e88e8 Result
    

    The patients whose tumor shrink significantly one month after radiotherapy had lower expression of SDH5 in tumor, and loss of SDH5 expression correlated with down regulation of DNA-PKcs^Thr2609 and ku86. More importantly, SDH5 can be directly detected in blood by qRT-PCR, and the result is consistent with that in tissue. And more exciting, patients with deficiency of SDH5 had longer PFS and OS after radiotherapy, and the results in blood and in tumor are consistent. To further verify the effect of SDH5 on radiosensitivity, in vivo experiments were carried out. In the orthotopic model, SDH5 knock down tumors showed higher radiation sensitivity with smaller volume. In SDH5 knock-out mice, lung epithelial cells exhibited elevated DNA damage after radiation. Moreover, our data indicated that SDH5 depletion causes P53 translocated from cytoplasm to nucleus, which enhances radiosensitivity of non-small cell lung cancer. Furthermore, consistent with in vivo data, the tumor growth was partially reversed when p53 was co-depleted with SDH5.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    In this experiment we found that SDH5 regulated radiosensitivity by P53 and it can be detected in tumor tissue. It is a suitable marker for predicting radiosensitivity. More than this, the expression of SDH5 can be directly measured by qRT-PCR in the blood, and it is consistent with that in the tumor tissue. This provides a novel non-invasive method for predicting the radiosensitivity of the patients unable to tolerant the biopsy.

    6f8b794f3246b0c1e1780bb4d4d5dc53