Squamous Cell Carcinoma of the Oropharynx

This randomized, prospective, multicenter phase II/III trial will study the reduction of radiation volume by eliminating radiotherapy (RT) to the elective neck using strictly defined surgical and radio-oncological standards to reduce radiotherapy-related long-term side effects without affecting locoregional control.

The study will evaluate the safety and effectiveness of a lower than standard dose of radiation for definitive or adjuvant treatment of head and neck squamous cell carcinomas.

Single center, non-randomized Phase II study enrolling Stage I-II p16+ oropharyngeal cancer patients to one of two de-escalation treatment paradigms: (1) receive surgery followed by observation or risk-adjusted adjuvant radiation (+/-chemo), or (2) individualized adaptive definitive chemoradiation (CRT).

Epidermoid Carcinoma of the Upper Aerodigestive Tract (CEVADS) is the 6th most common cancer worldwide. Despite current therapies (radiotherapy, surgery and chemotherapy), cancers of the Upper Aerodigestive Tract (UAT) have a poor prognosis, with a 10-year survival rate of no more than 20%. For recurrent or metastatic CEVADS, the therapeutic arsenal, based for many years on chemotherapy and anti-EGFR (Epidermal Growth Factor Receptor) agents, has been enriched by a new therapeutic class: PD-1 inhibitors. For CEVADS, PD-1 inhibitors have been approved for second-line treatment of nivolumab for over a year, and are now used in first-line treatment of pembrolizumab. The results of this therapeutic class in CEVADS are not as spectacular as for melanoma or bronchial cancer. Indeed, only 20% of patients have a favorable response, compared with half who experience disease progression. This low proportion of responders can be explained by tumor heterogeneity within CEVADS and poor patient selection. The only marker used to select patients is PD-L1 expression detected by ImmunoHistochemistry (IHC). However, it seems that this marker, described as imperfect, is still little explored in ENT. It needs to be compared with the expression of other cell lines in the tumor microenvironment, which could play an important role in resistance to PD-1 inhibitors. IHC identifies all macrophages using the CD68 marker, while the CD163 marker is specific to M2 macrophages. Other targets in the microenvironment are also being investigated, with the discovery of a Tertiary Lymphocyte Structure (TLS) in melanoma treated with immunotherapy. It therefore seems necessary to gain a better understanding of the mechanisms of tumor progression under immunotherapy in order to develop strategies to optimize response to treatment. This would enable better selection of patients likely to benefit from immunotherapy, and open up prospects for therapeutic combinations. The hypothesis is that macrophages, but also other cells and factors in the CEVADS microenvironment, play a decisive role in resistance to PD-1 inhibitors. The aim is therefore to continue these macrophage analyses, extend them to other cells in the microenvironment and link them to other prognostic factors under investigation. A prospective study will analyze tumor tissue during treatment with PD-1 inhibitors, in order to correlate all the factors studied with response or resistance to immunotherapies. In addition, the oral microbiota, in the lineage of the intestinal microbiota, has been shown to be highly stable over time and to play a role in the oncogenesis of certain cancers, notably CEVADS. Like the intestinal microbiota, it could also represent a prognostic factor in the response to immunotherapies. Of all the bacteria in this oral microbiota, one has been shown to play a major role: Fusobacterium nucleatum (F. nucleatum). However, little is known about the mechanism of action of intratumoral F. nucleatum on the development of CEVADS. In particular, it is thought to play a role in local cancer immunity, via macrophages, regulatory T cells (Tregs) and TLRs. Finally, it appears that specific antimicrobial T-cell responses may cross-react with tumor antigens, hence the importance of also analyzing the metabolome of commensal bacteria.The aim of this study was to evaluate the evolution of the presence of this bacterium in saliva, as well as the specific immune response to F. nucleatum in patients with CEVADS during immunotherapy treatment.

Prospective, open, non-interventional, multi-center clinical registry study with the aim to establish a comprehensive research platform reflecting the real-world treatment landscape for recurrent/metastatic head and neck tumor patients.

Volume and Dose De-Intensified Radiotherapy for p16+ Squamous Cell Carcinoma of the Oropharynx: A Multi-Centre, Single Arm Prospective Cohort Study

Based on the evidence summarized in the introduction, the clinician hypothesize that the detection of the presence and expression of HPV-DNA, certain miRNAs, and a certain mutational profile in the tissues and biological fluids of these patients, may have important prognostic and diagnostic value not only in HPV-related OPSCCs but also in HPV+ occult T. Accordingly, this study aims to aim to better characterize their potential as biomarkers and to detect the possibility of their their use to implement the sensitivity and specificity of radiological methodologies (PET-CT and MRI), already in use in clinical practice, for monitoring disease progression in this specific subgroup. Finally, by using the collected material to generate organoids and Patient Derived Xenograft (PDX), the study also aims to identify possible new molecular drugs, which could solve the problem of resistance to radiochemotherapy.