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Mizuki Nishino



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    MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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      MA25.09 - M1b Disease in the 8th Edition of IASLC Staging of Lung Cancer: Pattern of Single Extrathoracic Metastasis and Clinical Outcom (ID 11942)

      14:30 - 14:35  |  Author(s): Mizuki Nishino

      • Abstract
      • Presentation
      • Slides

      Background

      The 8th edition of IASLC staging of lung cancer has revised M classification and defined M1b disease for single extrathoracic metastasis, which is distinguished from M1c with multiple extrathoracic metastases. We investigated the prevalence of M1b disease in stage IV NSCLC patients (pts), and studied the pattern of single extrathoracic metastasis and its relationship with overall survival (OS).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      567 pts with stage IV NSCLC (236 males, 331 females, median age: 63) diagnosed in 2008-2012 were reviewed to determine M stage according to the 8th edition of IASLC staging of lung cancer (M1a: separate tumor nodules in a contralateral lobe, pleural/pericardial nodule or effusion; M1b: single extrathoracic metastasis; M1c: multiple extrathoracic metastasis in one or more organs). Clinical characteristics and OS were compared according to M stage.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 567 pts, 57 pts (10%; 95%CI: 7.6-13%) had M1b disease with single extrathoracic metastasis, while 119 pts (21%) had M1a and 391 pts (69%) had M1c disease. Squamous histology was more common in M1b (9/57; 16%) than in M1a (7/119; 6%) and M1c pts (22/391; 6%) (Fisher P=0.03). The median OS of M1b pts was 14.8 months (95%CI: 12.7-24.7 months), compared to 22.7 months (95%CI: 18.5-31.6 months) for M1a and 13.4 months (95%CI: 11.8-15.3 months) for M1c pts (log-rank P < 0.0001). Among 57 M1b pts, brain was the most common site of single metastasis (n=28; 49%), followed by bone (n=16; 28%), adrenal (n=7; 12%), liver (n=3; 5%), muscle (n=2; 4%), and distant node (n=1; 2%). M1b pts with liver metastasis had shorter OS than others (median OS: 8.1 vs. 16.1 months, log-rank P=0.046). Single metastasis in M1b pts were locally treated in 31 pts (54.5%). Brain metastasis was more frequently treated with local treatment than others (26/28, 92.9%vs. 5/29, 17%; p<0.0001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      M1b disease was noted in 10% of stage IV NSCLC pts. Squamous histology was more common in M1b than in M1a and M1c groups. Brain was the most common site of single metastasis and was often treated locally. Single liver metastasis in M1b disease was associated with shorter OS. The study characterized the unique clinical features of the new category of M1b disease among stage IV NSCLC.

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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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      P1.01-35 - Tumor Volume Analysis In ALK-Rearranged NSCLC Treated with Crizotinib: Identifying an Early Marker for Clinical Outcome (ID 11720)

      16:45 - 18:00  |  Author(s): Mizuki Nishino

      • Abstract

      Background

      Targeted inhibition of anaplastic lymphoma kinase (ALK) has been widely used for the treatment of advanced non-small-cell lung cancer (NSCLC) with ALK-rearrangement. We performed tumor volume analysis of ALK-rearranged advanced NSCLC treated with crizotinib to identify an early imaging marker that can predict clinical outcome.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Forty-two patients with advanced NSCLC harboring ALK-rearrangement (15 men, 27 women; median age: 55.7 years) treated with crizotinib as their first ALK-directed therapy at Dana-Farber Cancer Institute between November 2008 and June 2016. All patients had a follow-up chest CT scan at 8 +/- 3 weeks of therapy and had a dominant measurable lesion in the lung (≥1 cm) on baseline CT. Tumor volume of the dominant lung lesion was measured on baseline CT and follow-up CT at 8 +/- 3 weeks of therapy, using the previously validated technique on the volume analysis software (Vitrea ; Vital Images, Minnetonka, MN). The relationships between the 8-week volume change (%) and overall survival (OS) measured from the 8-week scan date were studied.

      4c3880bb027f159e801041b1021e88e8 Result

      The 8-week tumor volume change ranged from -99.3% to 117.5% (median: -57.7%). Using the 25 percentile of the 8-week volume change of -74%, 11 patients with >74% volume decrease at 8 weeks had a significantly longer OS compared to 31 patients with ≤74% decrease (Median OS: 92.0 months vs. 22.8 months, log-rank p=0.0048). In multivariable analyses using Cox proportional hazards models, the 8-week volume decrease of >74% remained as a significant factor associated with prolonged OS (HR=0.14, 95%CI: 0.03-0.59; Cox p=0.008) after adjusting for other significant variables including tumor stage at presentation (stage IV vs. others, HR=5.6, 95%CI: 1.29-24.3; p=0.02). Of the 31 patients with ≤74% decrease on the 8-week scan, best overall response by RECIST was partial response (PR) in 21 (68%), stable disease in 9 (29%), and progressive disease (PD) in one (3%). None of the 42 patients experienced RECIST-PD prior to the 8-week scan.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The 8-week tumor volume decrease of >74% on CT is significantly associated with longer OS in patients with ALK-rearranged NSCLC treated with crizotinib. The 8-week tumor volume analysis helps to identify patients who may benefit from alternative therapy in the early course of crizotinib therapy.

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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
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      P2.01-73 - Automated Image Analysis Tool for Tumor Volume Growth Rate to Guide Precision Cancer Therapy: EGFR-Mutant NSCLC as a Paradigm (ID 11971)

      16:45 - 18:00  |  Presenting Author(s): Mizuki Nishino

      • Abstract

      Background

      Imaging remains a crucial component in the evaluation of the therapeutic benefit of precision cancer therapy, because it objectively characterizes tumor burden changes during therapy and provides guides for treatment decisions. The purpose of the present study is to develop an automated analytic module for calculation of tumor growth rate from serial CT scans and evaluate the module functionality and reproducibility in a pilot cohort of advanced NSCLC patients with EGFR mutations treated with EGFR tyrosine kinase inhibitors.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The module utilized a commercially available image-processing workstation equipped with a validated tumor volume measurement tool. A novel analytic software module was programmed with the capability to record and display serial tumor volume changes and to calculate tumor volume growth rate over time and added to the workstation. The functionality and reproducibility of the module was evaluated using a pilot cohort of 24 EGFR-mutant patients treated with EGFR inhibitors by two independent thoracic radiologists.

      4c3880bb027f159e801041b1021e88e8 Result

      The module analyzed chest CT scans from 24 patients (5 males, 19 females; median age: 61) with a median of 8 scans per patient, totaling 227 scans and provided a graphical display with an automated calculation of tumor growth rate after the nadir volume for each patient. High inter and intraobserver agreements were noted for tumor growth rates, with concordance correlation coefficients of 0.9323 and 0.9668, respectively. Interpretation of slow versus fast tumor growth using previously identified threshold of ≤0.15/month had a perfect interobserver agreement (κ=1.00), and an excellent intraobserver agreement (κ=0.895).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The present study describes the development of an image analytic module for assessing tumor growth rate and the data demonstrates the functionality and reproducibility of the module in a pilot cohort of EGFR-mutant NSCLC patients treated with EGFR-TKI. The image analytic module is an initial step for clinical translation of the tumor growth rate approach to guide cancer treatment in precision oncology.

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