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Giovanni Rossi



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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • 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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      P1.04-15 - Computerized Tomography Texture Analysis as Biomarker of Benefit from Nivolumab in Advanced Non-Small Cell Lung Cancer (ID 13040)

      16:45 - 18:00  |  Author(s): Giovanni Rossi

      • Abstract

      Background

      While immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced non-small cell lung cancer (NSCLC), response assessment is a challenging task. Indeed, due to the peculiar mechanism of action of ICIs, the currently employed response evaluation criteria based on dimensional assessment might underestimate their activity. Computerized tomography texture analysis (CTTA) is an emerging approach belonging to the field of “radiomics” and based on the analysis of quantitative data extracted from imaging features; recently, correlations between CTTA and histopathologic as well as molecular characteristics of solid tumors were observed. Our aim is to determine whether parameters derived from CTTA might be used to assess the benefit from ICIs in advanced NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Among 74 patients (Pts) treated with nivolumab for advanced NSCLC, 35 had CT scans evaluable for CTTA and had undergone at least two assessments (at baseline and after 4 cycles). Each pulmonary lesion was evaluated by a radiologist experienced in CTTA, blinded to clinical and temporal data; 295 texture analysis parameters were obtained from each image using an open source software (MaZda, version 4.6). The variations of parameters derived from pre-set gray-level co-occurrence matrices (GLCM) before and after 4 cycles of nivolumab were determined and compared with clinical outcomes. Statistical analyses were performed using MedCalc Statistical Software (version 18).

      4c3880bb027f159e801041b1021e88e8 Result

      After a median follow up of 9.9 months, variations of GLCM features describing entropy were directly associated with overall survival (OS). Most notably, Pts with increase of entropy above the median value between baseline and the subsequent CT scan identified with a specific GLCM combination had longer OS (15.3 vs. 6.2 months; p= 0.044). This finding suggests that increased tissue heterogeneity during treatment, possibly caused by immune cells infiltration, might be associated with improved outcomes.

      8eea62084ca7e541d918e823422bd82e Conclusion

      CTTA might have a prognostic/predictive role during treatment with ICIs for NSCLC. Further analyses including clinical and histopathologic features are currently ongoing, in order to enlighten the biological mechanisms at the basis of our observations.

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • 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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      P2.03-28 - Whole Exome Sequencing to Discover Lung Tumor Predisposition in Women with Previous Breast Cancer (ID 13033)

      16:45 - 18:00  |  Author(s): Giovanni Rossi

      • Abstract

      Background

      During their life, women treated for breast cancer (BC) are at risk to develop lung cancer (LC); this risk is increased in smokers and if adjuvant radiation (aRT) was administered for BC. The relative risk of LC after treated BC ranges from 1.38 to 5.05. We hypothesized that genetic variants might predispose patients (Pts) to develop LC after BC. Our aim was to perform whole exome sequencing (WES) to identify genes associated with such predisposition.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      28 women who developed LC after BC (Study Population, SP) and 32 women treated for BC and with no secondary cancer after a follow-up ≥10 years (control population; CP) were enrolled. DNA was extracted from tumors and normal tissue samples from both SP and CP. Libraries were prepared with Agilent SureSelect All Exon kit and sequenced on Illumina HiSeq2500. Variant calling was performed with FreeBayes software.

      4c3880bb027f159e801041b1021e88e8 Result

      The median age of SP at BC diagnosis was 63.5 years (range: 47-76); the median interval between diagnosis of BC and occurrence of LC was 4.5 years (range: 0-11). 13 Pts (46%) were never-smokers and, among the 21 Pts who had received aRT, 13 (62%) developed ipsilateral LC. At somatic analysis, no common mutation among known driver genes was shared between each BC and LC pair. WES performed on BC and LC samples identified two mutational signatures (S1 and S2). S1 (C>T substitutions) was observed in all BC samples and 16/28 (57%) LC samples and was more frequent in never-smokers (11 vs. 5 Pts) and among Pts who developed ipsilateral LC after aRT (10 vs. 6 Pts). S2 (C>A transversions) was observed in 12/28 LC samples (43%) and was strongly associated with smoking habit (10 vs. 2 Pts). When compared to COSMIC libraries, S2 resulted similar to COSMIC 4, common in LC samples collected from smokers. Since S1 was largely shared between paired BC and LC samples, we explored the eventuality of a genetic predisposition to S1-related malignancies with a gene-based burden test over rare germline variants in normal tissue of S1-LC Pts compared to CP Pts; 249 candidate genes were identified (FDR<0.05).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data identify two mutational S underlying the LC development. Germline analysis suggests that genetic variants may contribute to increase the risk of LC after BC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

    • 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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      P2.04-02 - Predictive Value of Circulating Tumor Cells and Circulating Free DNA in NSCLC Patients Treated with Nivolumab (ID 13809)

      16:45 - 18:00  |  Author(s): Giovanni Rossi

      • Abstract

      Background

      Immunotherapy represents a dramatic change in the treatment of non small cell lung cancer (NSCLC), but nowadays prognostic and predictive factors of response to immune checkpoint inhibitors (ICIs) are still under debate. It has been observed that circulating biomarkers might have a prognostic role in lung cancer. The aim of this study was to determine whether circulating tumor cells (CTCs) as well as circulating free DNA (cfDNA) might predict the outcome of patients with advanced NSCLC treated with Nivolumab.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From May 2015 to April 2017 89 NSCLC patients were treated with Nivolumab as a second or further line of therapy. All patients underwent blood sample collection before the start of treatment (baseline) and after 4 and 7 cycles of Nivolumab to evaluate both biomarkers. CTCs were isolated from 3mL of blood by the filtration-based device ScreenCell Cyto (ScreenCell) according to manufacturer’s protocol. cfDNA was extracted from plasma using the QIAamp DNA Blood Mini Kit (Qiagen) and quantified (ng/mL) by qPCR method, using hTERT single copy gene. The median baseline CTC number and cfDNA content were used as cut-off values to discriminate patients with different outcomes. An univariate analysis was done to evaluate the overall survival (OS) in the study population based on CTC and cfDNA using the Kaplan Meyer method.

      4c3880bb027f159e801041b1021e88e8 Result

      The median CTC number and cfDNA at baseline were 2/3mL and 836.5 ng/mL, respectively. Median OS was 8.8 and 6.2 months for patients with baseline CTC ≤2 and >2, respectively (HR 1.53, 95% CI 0.96-2.42; p=0.072). Similarly, patients with high level of cfDNA > 836.5 ng/ml showed a worse OS as compared with those having lower cfDNA: 5.1 vs 9.4 months (HR 1.63, 95% CI 1.02-2-59; p=0.040).

      8eea62084ca7e541d918e823422bd82e Conclusion

      A statistically significant advantage in terms of OS was observed in the group of patients with baseline cfDNA below the median value. Similarly, a longer survival, although of borderline significance, was observed in the group of patients with baseline CTC ≤2. Longitudinal change evaluations of both circulating biomarkers compared to radiological tumor size are currently ongoing.

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