Immunotherapy for the prevention of high-risk oral disorders malignant transformation: the IMPEDE trial
Cristina Gurizzan,
Luigi Lorini,
Alberto Paderno,
Michele Tomasoni,
Gabriele Zigliani,
Anna Bozzola,
Laura Ardighieri,
Simonetta Battocchio,
Eliana Bignotti,
Antonella Ravaggi,
Chiara Romani,
Loris De Cecco,
Mara Serena Serafini,
Rosalba Miceli,
Elena Bardellini,
Alessandra Majorana,
Cesare Piazza,
Paolo Bossi
Affiliations
Cristina Gurizzan
Medical Oncology Unit, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili
Luigi Lorini
Medical Oncology Unit, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili
Alberto Paderno
Unit of Otorhinolaryngology – Head and Neck Surgery, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili
Michele Tomasoni
Unit of Otorhinolaryngology – Head and Neck Surgery, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili
Gabriele Zigliani
Unit of Otorhinolaryngology – Head and Neck Surgery, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili
Anna Bozzola
Unit of Pathology, Department of Molecular and Translational Medicine, University of Brescia, ASST-Spedali Civili
Laura Ardighieri
Unit of Pathology, Department of Molecular and Translational Medicine, University of Brescia, ASST-Spedali Civili
Simonetta Battocchio
Unit of Pathology, Department of Molecular and Translational Medicine, University of Brescia, ASST-Spedali Civili
Eliana Bignotti
‘Angelo Nocivelli’ Institute of Molecular Medicine, University of Brescia and ASST-Spedali Civili
Antonella Ravaggi
‘Angelo Nocivelli’ Institute of Molecular Medicine, University of Brescia and ASST-Spedali Civili
Chiara Romani
‘Angelo Nocivelli’ Institute of Molecular Medicine, University of Brescia and ASST-Spedali Civili
Loris De Cecco
Department of Applied Research and Technology Development, Integrated Biology Platform, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Mara Serena Serafini
Department of Applied Research and Technology Development, Integrated Biology Platform, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Rosalba Miceli
Department of Applied Research and Technical Development, Medical Statistics and Biometry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori
Elena Bardellini
Dental Clinic, Oral Medicine Unit - Department of Medical and Surgical Specialties, Radiological Science and Public Health University of Brescia, ASST-Spedali Civili
Alessandra Majorana
Dental Clinic, Oral Medicine Unit - Department of Medical and Surgical Specialties, Radiological Science and Public Health University of Brescia, ASST-Spedali Civili
Cesare Piazza
Unit of Otorhinolaryngology – Head and Neck Surgery, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili
Paolo Bossi
Medical Oncology Unit, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili
Abstract Background Oral Potentially Malignant Disorders (OPMD) have a non-negligible malignant transformation rate of up to 8%. Loss of heterozygosity (LOH) in critical chromosomal loci has proven to be the most effective marker in defining the risk of transformation and it is found in about 28% of OPMD and may therefore identify patients carrying higher risk. To date, clinical management of OPMD is limited to surgical excision and clinical surveillance, which however do not fully prevent oral cancer development. Immune system has been shown to play a key role in transformation surveillance mechanism and an immunosuppressive imbalance may be responsible for progression to cancer. Given all these considerations, we designed a clinical trial with the aim to prevent OPMD neoplastic transformation and revert the LOH status. Methods This is a phase II, open label, single arm, multicentric trial involving Italian referral centres and expected to enrol 80 patients out of a total of 175 screened. Patients who meet all inclusion criteria and test positive for LOH after an incisional biopsy of the OPMD will undergo a short course of immunotherapy with 4 administration of avelumab. After 6 months since treatment start, resection of the entire OPMD will be performed and LOH assessment will be repeated. The follow-up for malignant transformation and safety assessment will last 30 months from the end of treatment, for a total planned study duration of approximately 5.5 years. Discussion Restoring the activity of immune system through checkpoint inhibitor may play a crucial role against malignant transformation of OPMD by reverting the balance in favour of immune control and preventing cancer occurrence. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04504552 on 7th August 2020.
