Monitoring advanced Non-small cell lung cancer through plasma genotyping during Immunotherapy and targeted therapies: clinical feasibility and applications

Overview of the research line/lines:

Immunotherapy is one of the most important steps forward in the treatment of advanced non-small cell lung cancer (NSCLC). The only predictive marker available for clinical practice is PD-L1 expression, showing important limitations. Given the heterogeneity in response and its duration, the cost of the drugs and the availability of alternative options for advanced NSCLC, search of potential predictive markers is urgently needed. Considering that immune editing is a complex and dynamic mechanism and immune response might change during treatment, evaluation of dynamic biomarkers to measure tumor burden may open new perspectives in the context of personalization and duration of treatment.
On the other side, oncogene addicted NSCLC usually receive targeted agents achieving longer survival data and higher intracranial control with a optimal safety profile. However, tumor heterogeneity often drives to resistance mechanisms, potentially druggable with new agents. Liquid biopsy offers a non invasive and prompt tool to detect such resistance mechanisms, even before clinically relevant disease progression.
The main aim of this Project is to demonstrate that liquid biopsy can be used to monitor therapeutic efficacy of immune-modulating agents and detect druggable resistance mechanisms in oncogene addicted NSCLC patients

5 Publications

1. Liquid biopsy and non-small cell lung cancer: are we looking at the tip of the iceberg?
Bonanno L, Dal Maso A, Pavan A, Zulato E, Calvetti L, Pasello G, Guarneri V, Conte P, Indraccolo S.Br J Cancer. 2022 Mar 9. doi: 10.1038/s41416-022-01777-8. Online ahead of print.

2. Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome.
Pavan A, Bragadin AB, Calvetti L, Ferro A, Zulato E, Attili I, Nardo G, Dal Maso A, Frega S, Menin AG, Fassan M, Calabrese F, Pasello G, Guarneri V, Aprile G, Conte P, Rosell R, Indraccolo S, Bonanno L.Transl Lung Cancer Res. 2021 Jan;10(1):202-220

3. Clinical Impact of Plasma and Tissue Next-Generation Sequencing in Advanced Non-Small Cell Lung Cancer: A Real-World Experience.
Bonanno L, Pavan A, Ferro A, Calvetti L, Frega S, Pasello G, Aprile G, Guarneri V, Conte P; Rete Oncologica Veneta (ROV).Oncologist. 2020 Dec;25(12):e1996-e2005

4. Early assessment of KRAS mutation in cfDNA correlates with risk of progression and death in advanced non-small-cell lung cancer.
Zulato E, Attili I, Pavan A, Nardo G, Del Bianco P, Boscolo Bragadin A, Verza M, Pasqualini L, Pasello G, Fassan M, Calabrese F, Guarneri V, Amadori A, Conte P, Indraccolo S, Bonanno L.Br J Cancer. 2020 Jul;123(1):81-91

5. Clinical Features and Progression Pattern of Acquired T790M-positive Compared With T790M-negative EGFR Mutant Non-small-cell Lung Cancer: Catching Tumor and Clinical Heterogeneity Over Time Through Liquid Biopsy.
Dal Maso A, Lorenzi M, Roca E, Pilotto S, Macerelli M, Polo V, Cecere FL, Del Conte A, Nardo G, Buoro V, Scattolin D, Monteverdi S, Urso L, Zulato E, Frega S, Bonanno L, Indraccolo S, Calabrese F, Conte P, Pasello G.Clin Lung Cancer. 2020 Jan;21(1):1-14.e3


Funding
5x1000: Oncologia traslazionale e Biopsia liquida

People involved:
Guarneri Valentina, Full Professor
Dieci Maria Vittoria, Associate Professor
Pasello Giulia, Assistant Professor
Griguolo Gaia, Assistant Professor

Group members
Bonanno Laura, Frega Stefano, Ferro Alessandra, Dal Maso Alessandro




Tumor immune microenvironment and circulating biomarkers of inflammation for prognostic stratification and treatment outcome prediction of thoracic cancers circulating

Overview of the research line/lines:

This research line is focused on on pleural mesothelioma and lung cancer, with the aim of exploring tumor immune microenvironment and checkpoint expression as well as inflammatory circulating biomarkers, their prognostic role and modulation by systemic treatments and correlation with molecular pathways involved in cancer progression.

5    Publications

1. Detection of circulating immunosuppressive cytokines in malignant pleural mesothelioma patients for prognostic stratification.
Urso L, Silic-Benussi M, Boscolo A, Lorenzi M, Bonanno L, Lunardi F, Guarneri V, Calabrese F, Rea F, Conte P, Pasello G.Cytokine 2021

2. P14/ARF Positive Malignant Pleural Mesothelioma: A Phenotype With Distinct Immune Microenvironment.
Pezzuto F, Lunardi F, Vedovelli L, Fortarezza F, Urso L, Grosso F, Ceresoli GL, Kern I, Vlacic G, Faccioli E, Schiavon M, Gregori D, Rea F, Calabrese F, Pasello G. Front Oncol. 2021

3. Malignant pleural mesothelioma immune microenvironment and checkpoint expression: correlation with clinical-pathological features and intratumor heterogeneity over time.
Pasello G, Zago G, Lunardi F, Urso L, Kern I, Vlacic G, Grosso F, Mencoboni M, Ceresoli GL, Schiavon M, Pezzuto F, Pavan A, Vuljan SE, Del Bianco P, Conte P, Rea F, Calabrese F.Ann Oncol. 2018).

4. Immunoscore for Prognostic Stratification of Early Stage Non-Small-Cell Lung Cancer.
Boscolo A, Fortarezza F, Lunardi F, Comacchio G, Urso L, Frega S, Menis J, Bonanno L, Guarneri V, Rea F, Conte P, Calabrese F, Pasello G. Front Oncol. 2020

5. Tumor Immune-Infiltrate Landscape After Chemo-Radiotherapy in a Case Series of Patients with Non-small Cell Lung Cancer: Pretreatment Predictors and Correlation With Outcome.  
Pavan A, Ferro A, Fortarezza F, Schiavon M, Evangelista L, Pezzuto F, Lunardi F, Frega S, Bonanno L, Rea F, Guarneri V, Conte PF, Calabrese F, Pasello G. Oncologist 2022


Funding
RF-2018-12367604; and 5x1000 IOV, 2018
5x1000: Biopsia liquida

People involved:
Guarneri Valentina, Full Professor
Dieci Maria Vittoria, Associate Professor
Pasello Giulia, Assistant Professor
Griguolo Gaia, Asssitant Professor

Group members
Bonanno Laura, Frega Stefano, Ferro Alessandra, Dal Maso Alessandro




Real world studies on innovative anticancer drugs in lung cancer

Overview of the research line/lines:

Innovative drugs in oncology are approved and introduced in the clinical practice on the bases of pivotal clinical trials; as main limitations, clinical trials usually enroll highly selected patients and exclude some patients population which are often encounted in the clinical practice (e.g., elderly, poor performance status patients) . Real world evidence may close the gap between the ideal scenario of the clinical trial and the daily clinical practice; this is the rational for designing these multicenter studies both at regional and national level, aiming at investigating effectiveness and cost-effectiveness of innovative anticancer drugs such as targeted treatments and immune checkpoint inhibitors.

5 Publications

1. First-Line Osimertinib in Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer: Outcome and Safety in the Real World: FLOWER Study.
Lorenzi M, Ferro A, Cecere F, Scattolin D, Del Conte A, Follador A, Pilotto S, Polo V, Santarpia M, Chiari R, Pavan A, Dal Maso A, Da Ros V, Targato G, Vari S, Indraccolo S, Calabrese F, Frega S, Bonanno L, Conte PF, Guarneri V, Pasello G. Oncologist. 2022 Mar 4;27(2):87-e115

2. Multicenter Real-World Study on Effectiveness and Early Discontinuation Predictors in Patients With Non-small Cell Lung Cancer Receiving Nivolumab.
Pasello G, Lorenzi M, Calvetti L, Oliani C, Pavan A, Favaretto A, Palazzolo G, Giovanis P, Zustovich F, Bonetti A, Bernardi D, Mandarà M, Aprile G, Crivellaro G, Sinigaglia G, Tognazzo S, Morandi P, Bortolami A, Marino V, Bonanno L, Guarneri V, Conte P. Oncologist. 2022 Jun 8;27(6):e484-e493

3. Real world data in the era of Immune Checkpoint Inhibitors (ICIs): Increasing evidence and future applications in lung cancer.
Pasello G, Pavan A, Attili I, Bortolami A, Bonanno L, Menis J, Conte P, Guarneri V. Cancer Treat Rev. 2020 Jul;87:102031

4. Real-world data on treatment outcomes in EGFR-mutant non-small-cell lung cancer patients receiving osimertinib in second or further lines.
Dal Maso A, Lorenzi M, Ferro A, Pilotto S, Cecere F, Follador A, Polo V, Del Conte A, Sartori G, Giavarra M, Scattolin D, Indraccolo S, Frega S, De Maglio G, Menis J, Bonanno L, Calabrese F, Guarneri V, Conte P, Pasello G. Future Oncol. 2021 Jul;17(19):2513-2527

5. From Diagnostic-Therapeutic Pathways to Real-World Data: A Multicenter Prospective Study on Upfront Treatment for EGFR-Positive Non-Small Cell Lung Cancer (MOST Study).
Pasello G, Vicario G, Zustovich F, Oniga F, Gori S, Rosetti F, Bonetti A, Favaretto A, Toso S, Redelotti R, Santo A, Bernardi D, Giovanis P, Oliani C, Calvetti L, Gatti C, Palazzolo G, Baretta Z, Bortolami A, Bonanno L, Basso M, Menis J, Corte DD, Frega S, Guarneri V, Conte P; Veneto Oncology Network. Oncologist. 2019 Jun;24(6):e318-e326.

Funding
RSF-2017-00000557; CORIS 2019

People involved:
Guarneri Valentina, Full Professor
Dieci Maria Vittoria, Associate Professor
Pasello Giulia, Assistant Professor
Griguolo Gaia, Asssitant Professor

Group members
Bonanno Laura, Frega Stefano, Ferro Alessandra, Dal Maso Alessandro