Cristina Gurizzan1, Luigi Lorini1, Alberto Paderno2, Michele Tomasoni2, Gabriele Zigliani2, Anna Bozzola3, Laura Ardighieri3, Simonetta Battocchio3, Eliana Bignotti4, Antonella Ravaggi4, Chiara Romani4, Loris De Cecco5, Mara Serena Serafini5, Rosalba Miceli6, Elena Bardellini7, Alessandra Majorana7, Cesare Piazza2, Paolo Bossi8. 1. Medical Oncology Unit, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili, Piazzale Spedali Civili 1, 25123, Brescia, Italy. 2. Unit of Otorhinolaryngology - Head and Neck Surgery, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili, Brescia, Italy. 3. Unit of Pathology, Department of Molecular and Translational Medicine, University of Brescia, ASST-Spedali Civili, Brescia, Italy. 4. 'Angelo Nocivelli' Institute of Molecular Medicine, University of Brescia and ASST-Spedali Civili, Brescia, Italy. 5. Department of Applied Research and Technology Development, Integrated Biology Platform, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. 6. Department of Applied Research and Technical Development, Medical Statistics and Biometry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 7. Dental Clinic, Oral Medicine Unit - Department of Medical and Surgical Specialties, Radiological Science and Public Health University of Brescia, ASST-Spedali Civili, Brescia, Italy. 8. Medical Oncology Unit, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili, Piazzale Spedali Civili 1, 25123, Brescia, Italy. paolo.bossi@unibs.it.
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.
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.
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