Squamous Cell Carcinoma Head and Neck Cancer (HNSCC)

This is a phase 1, open-label, single-center study that plans to enroll 40 participants who will undergo surgical resection as SOC for HNSCC. This trial is designed to evaluate the safety of the safety of fluorescently labeled nivolumab (nivo800) as a molecular imaging agent. The study employs a dose-escalation design across four cohorts of 10 participants each. Participants in Cohorts 1-3 will receive an infusion of nivo followed by an infusion of nivo800 prior to standard-of-care surgical resection. The administration of unlabeled nivo will be administered approximately 2-3 weeks before surgery, followed by an administration of nivo800 administered 1-2 days prior to surgery.

In Portugal, approximately 2,424 new cases of head and neck cancer are diagnosed each year, of which 60% are already at an advanced stage, presenting with intense pain and dysphagia (difficulty swallowing). There is also marked social isolation due to communication difficulties, economic hardship, and facial disfigurement (altered facial appearance). As a result, patients frequently face challenges in accessing specialised palliative care services, encountering delays, fragmentation, or a complete absence of such care. The i-CARE-HN study is the solution: investigators aim to integrate outpatient palliative care with oncological treatment -namely chemoradiotherapy -at an earlier stage of the disease-when it is still limited to the throat and neck region, without metastasis (spread to other organs). This means multidisciplinary support from the outset of oncological treatment - symptom control, psychological support, and quality of life - without delaying the cure. It is like giving the patient a 'shield' against suffering, enabling them to complete treatment more efficiently. In the i-CARE-HN study, early palliative care aims to better manage patients' symptoms (such as pain, difficulty speaking, swallowing, breathing, dry mouth, loss of appetite, and anxiety), to clarify doubts, to support therapeutic decisions, and to strengthen communication between the patient and the team, without replacing the primary oncological treatment. Rather than waiting for symptoms to worsen before seeking help, this support will be provided throughout treatment with chemotherapy and radiotherapy. Through this simultaneous integration of outpatient palliative care into oncological treatment, investigators hope to improve patients' symptoms and quality of life, as well as clinical outcomes: fewer treatment interruptions, improved treatment tolerability, fewer emergency hospitalisations, and greater overall survival. Investigators will want to know how patients are feeling throughout the process, and to that end, will invite them to complete a survey at several points during the study. Responses to the questionnaires are critical to enabling the medical team to rapidly identify which participating patients present with the most significant symptoms and the greatest risk of complications. This study plans to recruit 64 patients aged 18 years or older, with a recent diagnosis of locally advanced, inoperable cancer, being followed on an outpatient basis at the IPO de Coimbra, IPO do Porto, and ULS de Coimbra, who will be invited to participate in the study. Should the patient agree to participate, some baseline data will be collected, and patients will subsequently be randomly assigned to one of two groups: one group will receive isolated chemoradiotherapy (standard treatment: cisplatin 100 mg/m² every 3 weeks- days 1, 22, and 49- and daily radiotherapy 70 Gy in 35 fractions over 7 weeks) and the other group will receive chemoradiotherapy alongside palliative care, on an outpatient basis (access to palliative care consultations). Patients randomised to the standard treatment group (chemoradiotherapy without a structured early palliative care intervention) will not have palliative care appointments systematically scheduled. However, should a referral to palliative care be requested, the patient may be directed to that clinical department.

This is a randomized, open-label, active-comparator-controlled, multi-regional, three-arm, phase 3 study comparing the efficacy and safety of ivonescimab in combination with ligufalimab to pembrolizumab and of ivonescimab alone to pembrolizumab as first-line treatment in patients with recurrent or metastatic (R/M) PD-L1-positive squamous cell carcinoma of the head and neck (HNSCC). The objective of this study is to improve first-line survival in patients with recurrent or metastatic PD-L1-positive HNSCC (CPS ≥ 1). Overall survival (OS) was chosen as the primary endpoint. Patients will receive the following treatment regimens in accordance with the study treatment plan until disease progression, death, intolerable toxicity, or the occurrence of another protocol-specified treatment discontinuation criterion, whichever occurs first. * ARM A: Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W) * ARM B: Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W), and ligufalimab (45 mg/kg iv, 120 min ± 15 min infusion, Q3W). * ARM C (control arm): Pembrolizumab (200 mg iv, 60 min ± 10 min infusion, Q3W). The total duration of treatment is up to 24 months

This study is for adult patients with head and neck cancer who are at risk of recurrence. The purpose of this study is to evaluate whether the use of Indocyanine Green (ICG) dye allows for better identification of tumor tissue during surgical procedures. Participation will include standard of care visits along with administration of ICG dye and imaging during surgery. Participation in this study will last approximately 6 weeks.

Hypo-fractionated radiotherapy reduces the OTT (overall treatment time) which may in turn reduce rapid accelerated repopulation of clonogenic cells during waiting period after surgery. If this holds true, there is a potential to achieve better loco-regional control in with PORT for HNSCC. There is a strong radiobiological and economic rationale for delivery hypo-fractionated radiotherapy in HNSCC. The HYPCON III trial will be aimed to reduce the number of fractions by 50% (30 fr to 15 fr)

This is a single-center, non-interventional, observational study that evaluates the correlation of circulating tumor DNA (ctDNA) testing to cancer relapse for participants with squamous cell carcinomas (HNC) of the head and neck mucosa and skin after curative-intent primary radiation or surgery.

Objective: The aim of this study is to characterize the inflammatory response in patients with head and neck cancer. More specifically, the study intend to investigate inflammatory and genetic differences between the primary tumor, the sentinel lymph node, and other regional lymph nodes. The investigator also aim to assess how the immunological and genetic responses differ in lymph nodes with and without metastases. To enable the detection of metastases in lymph nodes containing very few cancer cells, the investigator are developing a method to identify tumor cells using flow cytometry. Additionally, both tumor tissue and lymph nodes will undergo in vitro testing of checkpoint blockade therapy, a relatively new form of cancer immunotherapy. Methods: Biopsies from the primary tumor will be used to assess local inflammation. Fine-needle aspirates and dissected lymph node tissue will be analyzed to study inflammatory and genetic responses, as well as to detect tumor cells within these nodes. Blood samples from patients with head and neck cancer will be analyzed for inflammatory mediators. Lymph nodes from patients without cancer will be collected during benign neck surgeries. Immunological and genetic parameters from these control lymph nodes will be compared to those from the cancer patients to identify disease-specific patterns.