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, patients with 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.
In this context, the Clinical Oncology Section of DiSCOG has coordinated and conducted several translational research projects with the aim 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 (such as the REM study).

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. NGS detection of gene rearrangements and METexon14 mutations in liquid biopsy of advanced NSCLC patients: A study of two Italian centers.
Verzè M, Boscolo Bragadin A, Minari R, Pasello G, Perrone F, Scattolin D, Bordi P, Pluchino M, Leonetti A, Mazzaschi G, Bonatti F, Gnetti L, Bottarelli L, Zulato E, Nardo G, Dalle Fratte C, Padovan A, Bonanno L, Tiseo M, Indraccolo S. J Liq Biopsy. 2024 Feb 10;4:100143. doi: 10.1016/j.jlb.2024.100143. eCollection 2024 Jun.

3. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer.
Herbst RS, John T, Grohé C, Goldman JW, Kato T, Laktionov K, Bonanno L, Tiseo M, Majem M, Dómine M, Ahn MJ, Kowalski DM, Pérol M, Sriuranpong V, Özgüroğlu M, Bhetariya P, Markovets A, Rukazenkov Y, Muldoon C, Robichaux J, Hartmaier R, Tsuboi M, Wu YL. Nat Med. 2025 Mar 17. doi: 10.1038/s41591-025-03577-y.

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. Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer.
Boscolo Bragadin A, Del Bianco P, Zulato E, Attili I, Pavan A, Carlet J, Marra L, Guarneri V, Indraccolo S, Bonanno L. NPJ Precis Oncol. 2024 Oct 17;8(1):234. doi: 10.1038/s41698-024-00704-9. PMID: 39420036; PMCID: PMC11486993.

Funding
5x1000: Oncologia traslazionale e Biopsia liquida

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

Group members
Frega Stefano, Ferro Alessandra, Dal Maso Alessandro

 

Tumor immune microenvironment and circulating biomarkers for prognostic stratification and treatment outcome prediction of lung cancer

Overview of the research line/lines:
Circulating biomarkers detectable through liquid biopsy can represent a prognostic factor in patients with thoracic malignancies and may be used to predict the treatment outcome.

In this context, the Clinical Oncology Section of DiSCOG has coordinated and conducted several translational research projects with the aim of exploring tumor immune microenvironment and checkpoint expression as well as inflammatory circulating biomarkers and circulating free DNA, their prognostic role and modulation by systemic treatments and correlation with molecular pathways involved in cancer progression.

5    Publications

1. Extensive-stage small-cell lung cancer in patients receiving atezolizumab plus carboplatin-etoposide: stratification of outcome based on a composite score that combines gene expression profiling and immune characterization of microenvironment.
Tosi A, Lorenzi M, Del Bianco P, Roma A, Pavan A, Scapinello A, Resi MV, Bonanno L, Frega S, Calabrese F, Guarneri V, Rosato A, Pasello G. J Immunother Cancer. 2024 Jul 1;12(7):e008974. doi: 10.1136/jitc-2024-008974.

2. Sex-related differences in serum biomarker levels predict the activity and efficacy of immune checkpoint inhibitors in advanced melanoma and non-small cell lung cancer patients.
Pasello G, Fabricio ASC, Del Bianco P, Salizzato V, Favaretto A, Piccin L, Zustovich F, Fabozzi A, De Rossi C, Pigozzo J, De Nuzzo M, Cappelletto E, Bonanno L, Palleschi D, De Salvo GL, Guarneri V, Gion M, Chiarion-Sileni V. J Transl Med. 2024 Mar 5;22(1):242. doi: 10.1186/s12967-024-04920-6.

3. Liver kinase B1 expression is associated with improved prognosis and tumor immune microenvironment features in small cell lung cancer.
Dal Maso A, Ferrarini F, Esposito G, Minuzzo SA, Puggia AM, Pezzuto F, Zulato E, Bao LC, De Nuzzo M, Ferro A, Frega S, Pasello G, Calabrese F, Fassan M, Rea F, Guarneri V, Indraccolo S, Bonanno L. Front Oncol. 2025 Apr 4;15:1552506. doi: 10.3389/fonc.2025.1552506. eCollection 2025.

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, Associate Professor
Laura Bonanno, Assistant Professor
Griguolo Gaia, Assistant Professor
Federica Miglietta, Assistant Professor

Group members
Frega Stefano, Ferro Alessandra, Dal Maso Alessandro

Real world studies on innovative anticancer drugs in lung cancer

Overview of the research line/lines:

Innovative oncology drugs have been approved and introduced into clinical practice based on pivotal clinical trials. However, these trials often have important limitations, as they typically enroll highly selected patient populations and exclude groups frequently encountered in real-world practice, such as elderly patients or those with poor performance status. Real world evidence may close the gap between the ideal scenario of the clinical trial and the daily clinical practice. In this context, the Clinical Oncology Section of DiSCOG has coordinated and conducted multicentric 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. Osimertinib in Patients With Treatment-Naive EGFR-Mutant Non-small Cell Lung Cancer: Overall Survival, Post-progression Management and Budget Impact Analysis in Real-World.
Pasello G, Lorenzi M, Scattolin D, Del Conte A, Cecere F, Pavan A, Macerelli M, Polo V, Pilotto S, Santarpia M, Cumerlato E, Da Ros V, Targato G, Bortolami A, Bonanno L, Ferro A, Dal Maso A, Frega S, Guarneri V. Oncologist. 2024 Jul 5;29(7):596-608. doi: 10.1093/oncolo/oyae043.

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. 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. doi: 10.1634/theoncologist.2020-0148. Epub 2020 Jul 7.

4. Real-world impact of the introduction of chemo-immunotherapy in extended small cell lung cancer: a multicentric analysis.
Bonanno L, Calvetti L, Dal Maso A, Pavan A, Bao LC, De Nuzzo M, Frega S, Sartori G, Ferro A, Pasello G, Morandi P, Aprile G, Guarneri V. Front Immunol. 2024 Jan 22;15:1353889. doi: 10.3389/fimmu.2024.1353889. eCollection 2024.

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, Associate Professor
Laura Bonanno, Assistant Professor
Griguolo Gaia, Assistant Professor
Federica Miglietta, Assistant Professor

Group members
Frega Stefano, Ferro Alessandra, Dal Maso Alessandro

New treatment strategies, tumor microenvironment, circulating biomarkers and molecular profiling in rare thoracic cancers: lung neuroendocrine cancers, thymic tumors and mesothelioma

Overview of the research line/lines:

Thymic malignancies and mesothelioma represent a rare and heterogeneous subset of thoracic tumors, often associated with diagnostic challenges and limited therapeutic options. Despite recent advances in oncology, these cancers continue to show poor prognosis in advanced stages, underscoring the need for more effective and tailored treatment approaches. Comprehensive molecular profiling and an in-depth understanding of the tumor microenvironment are essential to uncover key oncogenic drivers and immune-related mechanisms that may serve as novel therapeutic targets. Moreover, the identification and validation of circulating biomarkers could offer non-invasive tools for early diagnosis, real-time disease monitoring, and dynamic treatment adjustment, ultimately paving the way toward precision medicine in this neglected area of thoracic oncology.

In this context, the Clinical Oncology Section of DiSCOG is coordinating and conducing several translational research projects with the aim to demonstrate the role of the microenvironment and circulating biomarkers in mesothelioma and thymic tumors (such as IMAGING-MESO and MONET studies); moreover, the Clinical Oncology Section of DiSCOG is coordinating and conducing the clinical phase II trial CHIMERA, enrolling patients with resectable mesothelioma to receive perioperative chemo-immunotherapy.

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. The emerging role of Schlafen-11 (SLFN11) in predicting response to anticancer treatments: Focus on small cell lung cancer.
Scattolin D, Maso AD, Ferro A, Frega S, Bonanno L, Guarneri V, Pasello G. Cancer Treat Rev. 2024 Jul;128:102768. doi: 10.1016/j.ctrv.2024.102768. Epub 2024 May 23.

5. Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial.
Pinto C, Zucali PA, Pagano M, Grosso F, Pasello G, Garassino MC, Tiseo M, Soto Parra H, Grossi F, Cappuzzo F, de Marinis F, Pedrazzoli P, Bonomi M, Gianoncelli L, Perrino M, Santoro A, Zanelli F, Bonelli C, Maconi A, Frega S, Gervasi E, Boni L, Ceresoli GL. Lancet Oncol. 2021 Oct;22(10):1438-1447. doi: 10.1016/S1470-2045(21)00404-6. Epub 2021 Sep 6.

Funding
5x1000 malattie rare IOV

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

Group members
Frega Stefano, Ferro Alessandra, Dal Maso Alessandro

Multidisciplinary management of thoracic malignancies and its impact on personalized therapeutic strategies

The multidisciplinary management of thoracic malignancies integrates the expertise of medical oncologists, thoracic surgeons, radiation oncologists, radiologists, and pathologists. This collaborative approach enables comprehensive patient evaluation and fosters individualized treatment planning. By combining diverse clinical perspectives and incorporating molecular and genomic profiling, multidisciplinary teams can tailor therapeutic strategies to the unique characteristics of each patient’s disease. This personalized approach improves treatment efficacy, enhances patient outcomes, and supports decision-making in complex cases, ultimately representing a cornerstone of modern thoracic oncology care.

In this context, the Clinical Oncology Section of DiSCOG is coordinating and conducting research projects with the aim to demonstrate the valuable role of the multidisciplinary approach in thoracic oncology.

5 Publications

1. The Multidisciplinary Approach in Stage III Non-Small Cell Lung Cancer over Ten Years: From Radiation Therapy Optimisation to Innovative Systemic Treatments.
Ferro A, Sepulcri M, Schiavon M, Scagliori E, Mancin E, Lunardi F, Gennaro G, Frega S, Dal Maso A, Bonanno L, Paronetto C, Caumo F, Calabrese F, Rea F, Guarneri V, Pasello G. Cancers (Basel). 2022 Nov 20;14(22):5700. doi: 10.3390/cancers14225700.

2. Clinical applications of radiomics and deep learning in breast and lung cancer: A narrative literature review on current evidence and future perspectives.
Ferro A, Bottosso M, Dieci MV, Scagliori E, Miglietta F, Aldegheri V, Bonanno L, Caumo F, Guarneri V, Griguolo G, Pasello G.Crit Rev Oncol Hematol. 2024 Nov;203:104479. doi: 10.1016/j.critrevonc.2024.104479. Epub 2024 Aug 14

3. Safety and Efficacy of Salvage Surgery after Treatment With Immune-Checkpoint Adjuvant Inhibitors for Advanced Non-Small Cell Lung Cancer: A Multicentric Study.
Schiavon M, Cannone G, Bertolaccini L, Gallina FT, Pezzuto F, Lorenzoni G, Facciolo F, Spaggiari L, Calabrese F, Rea F, Pasello G; Lung Oncology Group. J Surg Oncol. 2025 Mar;131(3):371-379. doi: 10.1002/jso.27920. Epub 2024 Sep 24

4. Multimodality treatment in synchronous oligometastatic NSCLC: Analysis of the ETOP CHESS trial.
Guckenberger M, Opitz I, Dellaporta T, Curioni-Fontecedro A, Frauenfelder T, Ribi K, Cerciello F, Sullivan I, Hendriks L, Dorta M, Callejo A, Aerts J, Addeo A, Dingemans AC, Pasello G, Provencio M, de Marinis F, Mederos-Alfonso N, Roschitzki-Voser H, Ruepp B, Haberecker M, Kammler R, Dafni U, Peters S, Stahel R; ETOP 14-18 CHESS collaborators. Lung Cancer. 2025 Apr 21;204:108553. doi: 10.1016/j.lungcan.2025.108553.

5. How the COVID-19 Pandemic Impacted on Integrated Care Pathways for Lung Cancer: The Parallel Experience of a COVID-Spared and a COVID-Dedicated Center.
Pasello G, Menis J, Pilotto S, Frega S, Belluomini L, Pezzuto F, Caliò A, Sepulcri M, Cernusco NLV, Schiavon M, Infante MV, Damin M, Micheletto C, Del Bianco P, Giovannetti R, Bonanno L, Fantoni U, Guarneri V, Calabrese F, Rea F, Milella M, Conte P. Front Oncol. 2021 Jun 28;11:669786. doi: 10.3389/fonc.2021.669786. eCollection 2021.

Funding
DISCOG DOR 2023; IOV ricerca corrente

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

Group members
Frega Stefano, Ferro Alessandra, Dal Maso Alessandro

Impact and management of innovative treatments in thoracic oncology: the spectrum of toxicities

The advent of innovative treatments—such as immune checkpoint inhibitors, targeted therapies, and advanced radiotherapy techniques—has significantly transformed the landscape of thoracic oncology. These therapies have improved survival outcomes, particularly in NSCLC, and have redefined treatment goals beyond disease control to include long-term remission and quality of life. However, their use may also be associated with potential detrimental effects, such as immune-related adverse events (irAEs), which require early recognition and appropriate management to avoid compromising therapeutic efficacy. Effective management of these therapies requires a multidisciplinary approach to address complex treatment decisions, monitor adverse events, and integrate molecular diagnostics. As a result, thoracic oncology teams must continuously adapt clinical pathways to ensure timely, personalized care that reflects the rapid evolution of available therapeutic options.

In this context, the Clinical Oncology Section of DiSCOG is actively coordinating, conducting, and collaborating on research studies aimed at reducing treatment-related toxicities—including those related to immunotherapy—while promoting the safe and effective integration of innovative therapies into daily clinical practice. Notably, the group has also contributed to the development of national guidelines, including the AIOM recommendations on the management of immunotherapy-related toxicities, underscoring its commitment to improving patient safety and treatment sustainability. These efforts are essential to optimize patient outcomes and ensure that personalized treatment strategies remain both efficacious and feasible in real-world settings.

5 publications

1. Peripheral Blood Markers Identify Risk of Immune-Related Toxicity in Advanced Non-Small Cell Lung Cancer Treated with Immune-Checkpoint Inhibitors.
Pavan A, Calvetti L, Dal Maso A, Attili I, Del Bianco P, Pasello G, Guarneri V, Aprile G, Conte P, Bonanno L. Oncologist. 2019 Aug;24(8):1128-1136. doi: 10.1634/theoncologist.2018-0563. Epub 2019 Apr 23.

2. Immune-related adverse events in patients treated with immunotherapy for locally advanced or metastatic NSCLC in real-world settings: a systematic review and meta-analysis.
Pasello G, Pavan A, De Nuzzo M, Frega S, Ferro A, Dal Maso A, Bonanno L, Guarneri V, Girardi F. Front Oncol. 2024 Jul 9;14:1415470. doi: 10.3389/fonc.2024.1415470. eCollection 2024.

3. Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial.
Majem M, Goldman JW, John T, Grohe C, Laktionov K, Kim SW, Kato T, Vu HV, Lu S, Li S, Lee KY, Akewanlop C, Yu CJ, de Marinis F, Bonanno L, Domine M, Shepherd FA, Atagi S, Zeng L, Kulkarni D, Medic N, Tsuboi M, Herbst RS, Wu YL. Clin Cancer Res. 2022 Jun 1;28(11):2286-2296. doi: 10.1158/1078-0432.CCR-21-3530.

4. Longitudinal liquid biopsy anticipates hyperprogression and early death in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors.
Zulato E, Del Bianco P, Nardo G, Attili I, Pavan A, Boscolo Bragadin A, Marra L, Pasello G, Fassan M, Calabrese F, Guarneri V, Conte PF, Indraccolo S, Bonanno L. Br J Cancer. 2022 Nov;127(11):2034-2042. doi: 10.1038/s41416-022-01978-1. Epub 2022 Sep 29. PMID: 36175621; PMCID: PMC9681746.

5. Immune-Related Diarrhea and Colitis in Non-small Cell Lung Cancers: Impact of Multidisciplinary Management in a Real-World Setting.
Bonanno L, Lorenzi M, Massa D, De Nuzzo M, Angerilli V, Zingone F, Barberio B, Russi A, Girardi F, Ferro A, Dal Maso A, Frega S, Pasello G, Dei Tos AP, Coppola M, Fassan M, Savarino EV, Guarneri V. Oncologist. 2024 Jan 5;29(1):e118-e130. doi: 10.1093/oncolo/oyad238.

Funding
SID 2024

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

Group members
Frega Stefano, Ferro Alessandra, Dal Maso Alessandro