Study end points & procedures
tumor, head and neck imaging, death, Toxicities, toxicities, head and neck lesions, Tumors, head and neck cancer-specific
TUMORS, ADVERSE EVENT, TUMOR, DISEASE
The primary outcome measure is the overall treatment response rate according to Response Evaluation Criteria in Solid Tumors 1.1. Follow-up imaging with CT, MRI or PET/CT will be obtained every five to six immunotherapy treatments. For the purposes of tumor measurements, follow-up imaging will be performed using the same modality (CT or MRI) used for baseline imaging measurements. PET/CT may be utilized for follow-up imaging at the clinician's discretion. Response in the target lesion(s) and in other, nontarget head and neck lesions will be assessed and documented during the course of the study by a fellowship-trained neuroradiologist with subspecialty expertise in head and neck imaging. The maximum response documented in the target lesion(s) will address the primary objective. Duration-of-response at the target lesion(s) will be defined as the duration of time from when the measurement criteria are met for complete or partial response (whichever is recorded first) to the first date of documented recurrent or progressive disease. PFS will be defined as the duration of time from registration to the time of progression, death or date of last contact; patients lost to follow-up will be censored. OS will be defined as the duration of time from registration to the date of death or date of last contact; patients lost to follow-up will be censored. The study treatment ends for all patients with the last administration of immunotherapy. Patients will be followed after the conclusion of treatment for PFS and OS outcomes. Subsequent visits can be accomplished in person or over the phone, and clinical and imaging data will be collected from medical records as available. Treatment toxicities will be monitored and documented during the treatment and for 30 days from the end of immunotherapy. Toxicities will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Patient-reported outcomes will be obtained at each time point using a targeted checklist of head and neck cancer-specific Patient-Reported Outcome–CTCAE version 1.0 items.Saliva and blood will be collected before each ICI treatment for the first five cycles and before RT on the first day of each QS treatment. For patients treated with subsequent QS cycles (i.e., second or third QS), samples will be collected before the ICI cycles that are administered before and after each additional QS. Levels of immunoregulatory miRNAs will be quantified in plasma using PCR-based techniques. Immune miRNA analysis will be utilized to create an immune response curve in order to select the best-response sample for in-depth immune response investigation, employing targeted analysis with single-cell RNA sequencing and complementary mass spectrometry-based omics (proteomics, metabolomics and lipidomics) on peripheral blood mononuclear cells and plasma. We will utilize an integrated data processing pipeline to align and interpret multiomics profiles to identify molecular drivers of response to ICI combined with QS RT. Expression of the top five candidate biomarkers identified, as determined by fold change and statistical significance, will be secondarily validated by western blot or mass spectrometry-based targeted analysis. Oral microbiota profiling will be performed using 16S rRNA gene sequencing to characterize the effect of ICI and the combination with QS RT on bacterial diversity and composition in saliva.