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Xinmin Yu



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    OA13 - Therapeutics and Radiation for Small Cell Lung Cancer (ID 927)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 10:30 - 12:00, Room 203 BD
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      OA13.06 - Final Report of a Prospective Randomized Study on Thoracic Radiotherapy Target Volumes in Limited-stage Small Cell Lung Cancer with Radiation Dosimetric and Pathologic Analyses (ID 11970)

      11:25 - 11:35  |  Author(s): Xinmin Yu

      • Abstract
      • Presentation
      • Slides

      Background

      The interim analysis of our prospective trial, which compared irradiation to pre-chemotherapy or post-chemotherapy tumour extent while application of involved field radiotherapy (IFRT) for limited-stage small cell lung cancer (SCLC), showed that reduced field did not result in increased local/regional out-field recurrence. This report presents the final results of the clinical study with radiation dosimetric and pathologic analysis as interpretations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Chemotherapy consisted of 4 to 6 cycles of etoposide and cisplatin (EP). After 2 cycles of EP, patients were randomly assigned to receive thoracic radiotherapy (TRT) to either the post- or pre-chemotherapy tumour extent as study arm or control. TRT was administered concurrently with cycle 3 chemotherapy. IFRT was applied for both arms. The lymph node regions (groups 1 to 10) were contoured in treatment planning system. The intentional or incidental radiation doses to each lymph node regions were recorded. Patients with stage T1-2N0-1M0 SCLC received radical lobectomy. The minimal distances between microscopic nidus and the edge of gross tumor were measured. The clinical target volume of the primary tumor (CTV-T) was defined as the margins covering 95% of microscopic disease extension.

      4c3880bb027f159e801041b1021e88e8 Result

      Between June, 2002 and January, 2017, 159 and 150 patients were randomly assigned to study arm or control. The 1-, 3-, and 5-year local/regional progression free probability were 79.4%, 60.1% and 60.1% respectively in the study arm versus 79.8%, 64.5%, and 57.3% in the control (p=0.73). The median overall survival (OS) time was 22.1 months in the study arm (95% CI, 18.2-26.0) and 26.9 months (95% CI, 23.5-30.3) in the control, the 1-, 3-, 5-, and 7-year OS rates were 81.1%, 31.6%, 23.9% and 22.2% respectively in the study arm versus 85.3%, 36.6%, 26.1% and 20.0% in the control arm (p=0.51). A total of 1680 lymph node regions in 105 patients were contoured. The lymph node regions that received incidental radiation doses over 30Gy were: 7, 3P, 4L, 6, 4R, 5 and 2L. Eight patients were enrolled in the pathologic evaluation of CTV-T. The median range of CTV-T in patients received or did not receive neoadjuvant chemotherapy were 0.4mm and 1.7mm respectively, a margin of 1.4mm and 10.2mm could cover 95% of microscopic nidus extension respectively (p=0.00).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Irradiating post-chemotherapy tumour extent and applicant of IFRT didn't increase local/regional failure, and the OS difference wasn't statistically significant between the two arms. TRT could be limited to post-chemotherapy tumour extent, while IFRT could be routinely applied for limited-stage SCLC patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-43 - Next-Generation Sequencing in the Exploration of Genetic Heterogeneity for Lung Adenocarcinoma Patients with EGFR Activating Mutations (ID 11194)

      16:45 - 18:00  |  Author(s): Xinmin Yu

      • Abstract
      • Slides

      Background

      Increasing evidence leads to a ratiocination that genetic heterogeneity of the lung adenocarcinoma patients with sensitive EGFR mutations may impact clinical responses and outcomes to EGFR-TKIs.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed targeted NGS with a gene panel covering 416 cancer-related genes to profile genetic characteristics of 69 lung adenocarcinoma patients with activating EGFR mutations and assessed the contribution of targeted NGS to exploration of genetic heterogeneity of such cohort.

      4c3880bb027f159e801041b1021e88e8 Result

      We detected total 200 actionable genetic alterations (mean 2.9 variations per patient, range: 1-7 variations) in tumor DNA and 140 actionable genetic alterations (mean 2.0 variations per patient, range: 0-5 variations) in matched plasma ctDNA, respectively. The concurrent genes with the highest mutation rate were TP53 (observed in 72.5% patients), other uncommon EGFR mutations (observed in 21.7% patients), EGFR amplification (observed in 20.3% patients), RB1 (observed in 10.1% patients), PIK3CA (observed in 7.2% patients), and MYC (observed in 5.8% patients). NGS provides EGFR mutation detection in plasma with a test sensitivity of 88.2% and specificity of 100.0%. Novel mutations potentially related to primary drug resistance were identified including: CDC73, SMAD4, and CTNNB1 missense mutations; RB1, ARID1A, ARID2, DNMT3A, STK11, and ATR frameshift indel; CDKN2B-PATA31D1, NFKBIA-OR11H12 fusion gene; PRKCI, CCNE1, MCL1, ARAF copy number gain; RB1 loss. The pathways analysis showed that unique pathways in the primary resistant cohort included: 1) immune related pathways: Toll-like receptor signaling pathway, T cell receptor signaling pathway; 2) epithelial-mesenchymal transition (EMT) related pathways: TGF-beta signaling pathway; 3) downstream pathway of EGFR: PIK3CA/AKT/mTOR signaling pathway; 4) cell function related pathways: Mismatch repair pathway, AMPK signaling pathway, TNF signaling pathway, Notch signaling pathway, and Transcriptional misregulation in cancer.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In conclusion, we note the complexity and heterogeneity of activating EGFR-mutant lung adenocarcinoma that may confer primary resistance to EGFR TKI using NGS platform. This study highlights the advantage of the NGS than traditional methods on testing EGFR mutations, enabling further refinement in sub-classification for the improved personalization of lung cancer treatment.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 944)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.12-01 - A Single-Arm Multi-Center Phase II Study of Apatinib in Patients with ES-SCLC After Second/Third-Line Chemotherapy (ID 12960)

      16:45 - 18:00  |  Author(s): Xinmin Yu

      • Abstract
      • Slides

      Background

      The survival of patients (pts) with extensive-stage small-cell lung cancer (ES-SCLC) was poor. And the standard treatment strategies have not yet been established for those who failed from second/third-line chemotherapy. Apatinib, a vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, has been shown anti-cancer activity and manageable toxicities in several solid cancers.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A single-arm multi-center phase II study was designed to determine the efficacy and safety of apatinib in pts with ES-SCLC after second/third-line chemotherapy (clinical trial information: NCT02945852). The inclusion criteria mainly included aged 18-75 years; pathologically confirmed SCLC; received chemotherapy with two or three regimens previously, including first-line platinum-based regimen. Pts were treated with afatinib 500 mg/day p.o. until tumor progression or lack of tolerability. One treatment cycle was 28 days long. The full analysis set included patients who received at least one cycle of treatment. Treatment interruptions or dose reductions were allowed when grade 3 hematologic or grade 2 nonhematologic toxicities occurred. The primary endpoint is progression-free survival(PFS); secondary endpoint includes the safety of afatinib, overall survival (OS), objective response rate (ORR) and disease control rate (DCR).

      4c3880bb027f159e801041b1021e88e8 Result

      As of Mar 2018, 40 pts from 3 institutions were recruited into the trial. Median age was 60 years, and 37 pts were male (92.5%). 17/40 (42.5%) pts experienced dose reduction or treatment interruptions. Followed up to Apr 26, 2018, the median during time of afatinib treatment was 80 days and 36 pts were eligible for assessing tumor responses. In the 36 pts, 8 (22.2%) pts achieved partial responses [PR], 20 (55.5%) pts achieved stable disease [SD] and 8 (22.2%) pts were assessed as progressive disease [PD]. The ORR was 22.2% (8 pts PR) and the DCR was 77.8% (8 pts PR, 20 pts SD). During the follow-up, a total of 25 pts died. The median PFS and OS was 86 days and 105 days, respectively. The most common adverse events were anemia (69.4%, 25/36), hand-foot syndrome (61.1%, 22/36), urine protein (55.6%, 20/36), hypertension (52.8%, 19/36) and fatigue (44.4%, 16/36). The related grade 3-4 toxicities included hypertension (47.2%, 17/36), hand-foot syndrome (5.6%, 2/36), Oral ulcer (5.6%, 2/36) and elevated aminotransferase (5.6%, 2/36).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this prospective phase II trial, apatinib showed encouraging durable response rates and survival in patients with ES-SCLC after second/third-line chemotherapy, with an acceptable safety profile.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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