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Ugo Pastorino
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MA03 - Lung Cancer Screening - Next Step (ID 896)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 206 AC
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MA03.03 - Prolonged Low-Dose Computed Tomography (LDCT) Screening Beyond 5 Years Reduces Overall and Lung Cancer Specific Mortality (ID 13227)
10:40 - 10:45 | Presenting Author(s): Ugo Pastorino
- Abstract
- Presentation
Background
The National Lung Screening Trial (NLST) showed that lung cancer screening (LCS) by low-dose computed tomography (LDCT) improves the overall survival. The NLST and most of the LCS trials were limited to a 5-year period, therefore there is no prospective evidence about the optimal duration of LCS. The aim of this study was to assess the potential benefit of long term LC screening beyond 5 years, notably its effect in 10-year overall and LC specific mortality.
a9ded1e5ce5d75814730bb4caaf49419 Method
The Multicenter Italian Lung Detection (MILD) trial prospectively enrolled 4,099 participants, randomized to either LDCT arm (n=2,376) or control arm (n=1,723); 38,561 person-years of follow-up were accumulated between 2005 and March 2017. The primary outcomes were 10-year overall and LC specific mortality. Moreover, a Landmark Analysis was used to test the long-term effect of LCS, beyond 5 years (notably by selective exclusion of events that occurred < 5 years). Cumulative mortality were evaluated using Kaplan-Meier estimator and differences among groups were tested using Log-rank test, adjusted for sex, age and pack-years. The prognostic value of assigned arm in predicting mortality was investigated by Cox’s proportional-hazard’s regression adjusted for the above variables.
4c3880bb027f159e801041b1021e88e8 Result
In the whole 10-year LCS, LDCT arm showed a protective non-statistically significant trend for reduction of overall mortality (HR: 0.82, 95% CI 0.63 to 1.07) and a significant 41% reduced risk of LC mortality (HR 0.59, 95% CI 0.38 to 0.92), compared to the control arm.
Beyond the 5th year of screening, LDCT arm showed a significant 29% reduction of overall mortality (HR: 0.71, 95% CI 0.50 to 0.99), and a significant 62% reduced risk of LC mortality (HR 0.38, 95% CI 0.20 to 0.74) (Figure 1).
8eea62084ca7e541d918e823422bd82e Conclusion
Prolonged LDCT screening beyond 5 years reduces overall mortality, and it is most beneficial in further reduction of LC specific mortality.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA04 - Novel Approaches with IO (ID 900)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
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MA04.07 - MicroRNA-Based Liquid Biopsy Combines with PD-L1 Tumor Expression to Predict Response to Immunotherapy in Advance NSCLC Patients (ID 12566)
14:10 - 14:15 | Author(s): Ugo Pastorino
- Abstract
- Presentation
Background
The advent of the new immune checkpoint inhibitors (ICIs) targeting the PD-1/L1 axis drastically improves survival of advance non-small-cell lung cancer (NSCLC) patients. However, only a limited subset of patients actually benefits of ICIs treatment and PD-L1 as predictive biomarker has a limited efficacy. We have previously identified a plasma microRNA-signature classifier (MSC) reflecting a circulating tumor-host interaction with diagnostic and prognostic value in low-dose computed tomography (LDCT) lung cancer screening trials.
a9ded1e5ce5d75814730bb4caaf49419 Method
The tumor immune contexture of 40 LDCT-screening detected lung tumors was characterized by the “cell-type identification by estimating relative subsets of RNA transcripts” (CIBERSORT) software. In a consecutive series of 84 advanced lung cancer patients treated with ICIs, both plasma and tissue samples were collected and prospectively analyzed. Both 2-years progression free (PFS) and overall survival (OS) in strata of plasma MSC risk level alone or combined with tumor PD-L1 expression were evaluated in univariate and multivariate analysis by log-rank test and Cox proportional hazards models.
4c3880bb027f159e801041b1021e88e8 Result
A pro-tumorigenic immune contexture was identified in tumors of MSC high risk patients. Lower levels of cytotoxic CD8+ and CD4+ T cells and increased levels of Tregs, γδ T Cells, M2 macrophages characterized these tumors. In addition, genes differentially expressed according to MSC risk level (high vs. intermediate and low) were associated with 5-years OS in the screening series (p-values=0.02), as well as in additional 1000 cases from The Cancer Genome Atlas database (p-values<0.01). In the 84 advanced NSCLC patients treated with ICIs, the PFS hazard ratio ranged from 0.44 (95%CI: 0.25-0.75) of PD-L1 (adjusted p-value=0.005) and 0.38 (95%CI:0.2-0.73) of MSC (adjusted p-value=0.004) alone, to 0.25 (95%CI: 0.14-0.45) if combined (adjusted p-value<0.0001). In the subgroup of 45 patients with both plasma and tumor tissue available, the combination of MSC and PD-L1 stratified patients in three groups with 2-years PFS ranging from 25%to 10% and 0% (p-value=0.01) according to the presence of 2, 1 or 0 favorable markers, respectively. Similar results were obtained when considering OS, where the median survival time for patients with no favorable markers was 5.6 months (p-value<0.0001).
8eea62084ca7e541d918e823422bd82e Conclusion
Overall, these findings suggest that a circulating microRNA-based risk level, reflecting an altered tumor immune contexture, could implement PD-L1 tumor tissue expression as predictive biomarkers of response to immunotherapy.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P3.08 - Oligometastatic NSCLC (Not CME Accredited Session) (ID 974)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.08-04 - OMEGA, A Randomized Trial of Local Ablative Therapy Vs. Conventional Treatment in Oligometastatic NSCLC – Trial in Progress (ID 13971)
12:00 - 13:30 | Author(s): Ugo Pastorino
- Abstract
Background
A recent randomized phase 2 study has shown that local ablative therapy in addition to systemic treatment was superior to maintenance therapy in prolonging disease-free survival in NSCLC patients harboring up to three metastatic sites.
Oligometastatic lung cancer (OM-NSCLC) seems thus to be associated with a better prognosis than usual Stage IV non-small cell lung cancer when radical local therapy of all metastatic sites is administered but the impact of such an approach on overall survival and quality of life remains unclear
a9ded1e5ce5d75814730bb4caaf49419 Method
A consortium of tertiary referral centres involved in Lung Cancer management at the national level was established with the aim of setting up a randomized trial addressing this issue
4c3880bb027f159e801041b1021e88e8 Result
A randomized trial of local ablative therapy in OM-NSCLC patients with potentially resectable or locally controlled primary tumors has been designed and 7 tertiary referral centers agreed to participate
Patients with synchronous or metachronous oligometastatic lung cancer (1-3 metastatic lesions) will be randomized to local ablative therapy + standard treatment Vs. standard treatment.
Balancing between study arms will be performed according to synchronous vs. metachronous presentation, Number of oligometastases, Nodal status and Oncogene-addiction or PDL-1 expression.
Primary outcome will be Overall Survival (OS) from randomization. The sample size is set to 195 patients.
Inclusion criteria include adequate performance status, primary tumor controlled or controllable staging with whole-body FDG PET scan and brain MRI, fit to receive at least 3 cycles of platinum-based doublet chemotherapy, or immunotherapy or targeted agents according to molecular profile.
Exclusion criteria include cerebral oligometastasis alone (will receive local therapy in any case),
metastasis in sites where normal radiotherapy constraints cannot be met, multiple subsolid nodules in the absence of extrapulmonary metastasis, prior malignant tumor with some exceptions, relevant co-morbidities that would significantly reduce life expectancy on their own,
Disease state and life status assessed on a 2-monthly basis by physical examination, whole-body CT scan plus repeat PET-scan if needed and Brain MRI if brain metastasis at enrolment. Toxicity and adverse events will be assessed according to NCI-Common Terminology Criteria. Quality of life will be assessed at randomization and after six months by the SF36/LCSS.
8eea62084ca7e541d918e823422bd82e Conclusion
There is a clear need for randomized controlled trials with overall survival as their main endpoint to confirm whether local ablative therapy indeed has a role in the management of oligometastatic lung cancer. The Omega trial will try to respond to such a need.
6f8b794f3246b0c1e1780bb4d4d5dc53
