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Francesco Guerrera



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    MA20 - Thymic Tumors: From Molecular to Clinical Results and New Challenges in Other Rare Thoracic Tumors (ID 149)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 1
    • Now Available
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      MA20.07 - Thymomectomy and Total Thymectomy or Simple Thymomectomy for Early Stage Thymoma Without Myasthenia Gravis: An ESTS Thymic Working Group Study (Now Available) (ID 1683)

      11:30 - 13:00  |  Presenting Author(s): Francesco Guerrera

      • Abstract
      • Presentation
      • Slides

      Background

      Resection of thymic tumors has traditionally included removal of the tumor and the thymus gland (thymothymomectomy). Nevertheless, in recent years, some authors questioned the need to remove the thymus gland in non-MG thymomas, suggesting that resection of the tumor (simple-thymomectomy) is enough from an oncological point of view in Stage I (TNM stage classification) thymoma patients. The aim of our study was to compare short- and long-term outcome of thymothymomectomy vs. simple-thymomectomy using European Society of Thoracic Surgeons (ESTS) Thymic Database.

      Method

      We investigated 1131 patients with thymic epithelial tumors included in the ESTS-Thymic Database. Three-hundred twenty-four clinical stage I (cT1N0M0, according to the 8th edition of the UICC/AJCC TNM stage classification) without Myasthenia Gravis (non-MG) thymoma cases were evaluated from 23 contributing centers (2000-2017), of which 300 (93%) thymothymomectomy and 24 (7%) simple-thymomectomy. Surgical upstaging was evaluated. In pathological stage I, we compared the completeness of resection, the rate of complications, the 30-day mortality, the overall survival and the disease-free survival (DFS).

      Result

      Overall, we observed an upstaging to stage III in 10 (3%) patients. We did not observe any significant difference between the two techniques in terms of the completeness of resection, the rate of complications and the 30-day mortality. The 5-year overall survival rate was 94% in the thymothymomectomy group and 56% in the simple-thymomectomy group (Figure 1 - P= 0.0004). The 5-year DFS was 95% in the thymothymomectomy group and 82% in the simple-thymomectomy group (Figure 1 -P= 0.013).

      figure 1.png

      Conclusion

      Patients affected by stage I TNM non-MG thymoma submitted to thymothymomectomy presented a significantly better DFS and overall survival than those submitted to simple-thymomectomy. Thymothymomectomy should be considered the procedure of choice in Stage I TNM non-MG thymomas, also considering the not negligible rate of pathological upstaging.

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    P2.06 - Mesothelioma (ID 170)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.06-23 - The Accuracy of Video-Assisted Thoracic Surgery Pleural Biopsy in Patients with Suspected Malignant Pleural Mesothelioma: A Real-Life Study (Now Available) (ID 1690)

      10:15 - 18:15  |  Presenting Author(s): Francesco Guerrera

      • Abstract
      • Slides

      Background

      The heritage of occupational and environmental asbestos exposure in Piedmont, Italy, is an enduring epidemic of malignant pleural mesothelioma (MPM). Pleural biopsy (PB) performed via thoracoscopy (or video-assisted thoracic surgery (VATS)) remains the diagnostic gold standard for patients with suspected mesothelioma. The aim of our study was to investigate the accuracy of PB via VATS and to analyze the diagnostic path of the patients who experienced an initial MPM misdiagnosis.

      Method

      Patients who underwent PB by VATS for suspected MPM from 2004 to 2013 were analyzed . The Registry of Malignant Mesothelioma (RMM) records were examined to crosscheck incident cases and to recognize misdiagnosed MPM. Sensitivity and specificity of the initial PB assessment versus the final classification of cases by RMM were evaluated. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using log-rank test.

      Result

      km_mpm.png

      Data of 552 patients were analyzed. Of those, MPM was diagnosed in 178 cases (32%) and no false-positive PBs were observed. Sensitivity and specificity were 93% and 100%, respectively. The number of false-negative PBs was 14 (2%). Of those, 10 (71%) had an initial diagnosis of chronic pleuritis, 3 (28.5%) of atypical mesothelial proliferation and 1 had reactive mesothelial proliferation. All of them reported a history of asbestos exposure and the correct diagnosis was reached after a median of 160 days (interquartile range 86-243) as follow: 9 (64%) after a further PB by VATS, 3 (22%) by cytology examination of a pleural effusion, 1 (7%) by fine-needle biopsy and 1 (7%) by open surgery . The median survival time of the patients with eventual MPM diagnosis was 13.8 months (CI 95%: 10.3-16.6). ). One- and 4-year survival were 52% and 10% in MPM PB positive cases and 50% and 19% in false-negative cases (P=0.66) (Figure 1).

      Conclusion

      When a history of asbestos exposure is reported and a strong clinical suspicion persists after a negative PB, iterative biopsy attempts should be considered. In high-volume centers, MPM misdiagnosis rate remains small and future advancement in diagnostic technologies could further increase the accuracy of diagnosis.

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    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.09-18 - Lymphocyte Infiltration Pattern and STING Expression Identify Different Prognostic Groups in Early Stage NSCLC (ID 2536)

      10:15 - 18:15  |  Author(s): Francesco Guerrera

      • Abstract
      • Slides

      Background

      Lymphocyte infiltration has been described has a potential biomarker of lung cancer patients’ survival. Different studies de-convoluted immune cell compartment (i.e. stromal CD8 density) trying to identify clinically relevant immune patterns.

      Method

      A series of 178 early-stage (IB-IIIA) NSCLC has been retrospectively collected at Department of Oncology, San Luigi Hospital (Orbassano, Italy). From Formalin-Fixed and Paraffine-Embedeed (FFPE) tumor blocks, Tissue Microarrays (TMA) were constructed (4 cores were selected for each case). Lymphocyte infiltration pattern was determined by light-microscopy on Hemathoxylin-Eosin (HE) whole slides. Immunohistochemistry was performed as follow: CD8 (SP57) and STING (D2P2F) antibodies were tested with Ventana Benchmark and PD-L1 (22C3) with Dako Autostainer. Infiltration pattern has been clustered in 4 different categories: brisk-diffuse, non-brisk multifocal, non-brisk focal and none. CD8 was quantified as positivity percentage, PD-L1 through TPS (<1%, 1-49% and ≥50%) and STING taking advantage of H-score. Overall survival (OS) and Progression Free Survival (PFS) were estimated using the Kaplan-Meier method and compared using log-rank test.

      Result

      Most represented patients had following features: male (119-71%), current or previous smokers (145-82%), stage II (94-53%) and adenocarcinoma histology (119-67%). Distribution of lymphocyte infiltration pattern was: 110 cases with brisk-diffuse (62%), 56 with non-brisk (multi-focal and focal) (31%) and 12 with none pattern (7%). CD8 positivity was distributed in 3 categories: high (66 - 37%), intermediate (75 - 42%) and low (37 -21%) density. For PD-L1 TPS analyses 111 cases (62%) had <1%, 39 cases (22%) 1-49% and 28 cases (16%) >50%. STING high-expressors were 88 (49%) and low-expressors 90 cases (51%). Lastly, were identified 81 samples (45%) with STING positivity at high-density on immune cells (IC) and 97 samples (55%) with low-density. As expected, Brisk-infiltrated samples presented an higher CD8 density (p=0.015). At PFS analyses, STING IC resulted associated (p=0.05) with a worse PFS for high-density patients. At OS analyses, brisk lymphocyte infiltration pattern appeared to have a negative impact (p=0.05) and STING higher-expressors on tumor cells had a worse prognosis (p=0.04).

      Conclusion

      NSCLC with wider lymphocyte infiltration and expression of immune activation markers (as STING) appeared to be associated with a worse prognosis (PFS and OS). These date need further validation at multivariate analyses.

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    P2.17 - Treatment of Early Stage/Localized Disease (ID 189)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.17-29 - Impact of Second Predominant Pattern on Recurrence in Early Stage Resected Lung Adenocarcinoma: A Multicentric Study (Now Available) (ID 2515)

      10:15 - 18:15  |  Author(s): Francesco Guerrera

      • Abstract
      • Slides

      Background

      The ATS/ERS/IASLC adenocarcinoma classification allowed not only a better anatomical-pathological definition, but it showed a significant influence on long-term outcomes. It has been proposed that adenocarcinoma patterns could be divided in three groups according to their clinical and pathological behaviors: low (lepidic), moderate (papillary or acinar) and high grade (micropapillary and solid). Moreover, different patterns might mingle influencing biological features and prognosis. We focused on resected adenocarcinomas analyzing the impact of second predominant pattern on recurrence rate and Disease-Free Survival (DFS).

      Method

      We retrospectively collected all stage I and II lung adenocarcinoma operated on between January 2014 and December 2017 in seven European thoracic surgery departments. We selected all patients who underwent an anatomical resection with lymphadenectomy; patients with incomplete follow up, pure adenocarcinoma or those composed by more than two subtypes (if third pattern accounted for more than 10%) were excluded. Mucinous adenocarcinoma were considered separately from other patterns. DFS, incidence and localization of recurrence were calculated according to the second predominant pattern.

      Result

      Among 500 patients, 331 were selected. There were 186 male, mean age was 68.1 years (±SD 8.2) and 105 (31.7%) patients were active smokers at the moment of diagnosis. The majority of patients (271, 81.9%) underwent a lobectomy. Low, medium and high-grade first predominant pattern were 45 (13.6%), 208 (62.9%), 57 (17,2%) respectively and 21 cases were mucinous.

      Second predominant pattern was present as follow: acinar 96 (29%), lepidic 86 (26%), papillary 74 (22.4%), solid 29 (8.8%), micropapillary 26 (7.9%), 20 mucinous (6%). DFS analysis showed a significant impact of grade of the second predominant pattern (p=0.046), while first predominant pattern’s grade did not significantly impact on DFS (p=0.322). According to the subtypes of second predominant pattern, lepidic pattern showed a better mean DFS (56.1 versus 49.6 months, p=0.014) and a lower recurrence rate (p=0.018, and, in particular, a lower distant recurrence rate, p=0.016), while micropapillary had a worse DFS (42.3 versus 52.1 months, p=0014), higher recurrence rate (p=0.017, and in particular, a higher regional recurrence, p=0.038); moreover, also pleural invasion influenced DFS significantly (p=0.001). At multivariate analysis, lepidic second pattern and pleural invasion confirmed their influence on DFS (p=0.044, IC 0.28-0.98 and p=0.001, IC 1.36-3.4).

      When we analyzed the subgroup with only moderate grade (acinar and papillary) first predominant pattern (208 patients), lepidic and micropapillary second predominant patterns and pleural invasion confirmed their significant impact on DFS (p=0.015; p=0.021; 0.015 respectively).

      Conclusion

      Our multicentric study confirms the impact of adenocarcinoma patterns on recurrence rate and DFS. The second predominant pattern in early stage resected adenocarcinoma seems to play an important role in influencing the outcomes. Micropapillary and lepidic second pattern demonstrated to be significantly related to recurrence development and their presence should require different and dedicated postoperative management.

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