Xevinapant plus radiotherapy in resected, high-risk, cisplatin-ineligible LA SCCHN: the phase III XRay Vision study design.

There is a significant unmet need and lack of treatment options for patients with resected, high-risk, cisplatin-ineligible locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Xevinapant, a first-in-class, potent, oral, small-molecule IAP inhibitor, is thought to restore cancer cell sensitivity to chemotherapy and radiotherapy in clinical and preclinical studies. We describe the design of XRay Vision (NCT05386550), an international, randomized, double-blind, phase III study. Approximately 700 patients with resected, high-risk, cisplatin-ineligible LA SCCHN will be randomized 1:1 to receive 6 cycles of xevinapant or placebo, in combination with radiotherapy for the first 3 cycles. The primary end point is disease-free survival, and secondary end points include overall survival, health-related quality of life, and safety.

Squamous cell carcinoma is the most common form of head and neck cancer (SCCHN) and includes cancers of the lips, mouth, throat, tongue and voice box. It is called 'locally advanced' when the cancer has spread to nearby areas but not to other parts of the body. Few treatment options are available for people with locally advanced SCCHN who have had surgery and are unable to receive a type of chemotherapy called cisplatin. Xevinapant is being developed as a possible new type of cancer treatment. It is a liquid that is taken by mouth or given through a feeding tube. Adding xevinapant to the standard treatment ­ called radiotherapy ­ aims to make radiotherapy more effective against the cancer. Researchers have started a large, international, phase III study called XRay Vision to see if adding xevinapant to radiotherapy can help stop the cancer from coming back after surgery and help people live longer. Clinical Trial Registration: NCT05386550 (ClinicalTrials.gov).

Long-term results from a clinical study of xevinapant plus chemoradiotherapy in people with high-risk locally advanced squamous cell carcinoma of the head and neck: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: Squamous cell carcinoma of the head and neck (SCCHN) is the most common type of head and neck cancer. About half of the people with locally advanced (LA) SCCHN will have surgery to remove their cancer. For people who do not have surgery, chemoradiotherapy is the standard treatment, with the aim of fully removing the cancer. However, in many people, this treatment does not completely kill the cancer. This summary presents the main results of a phase 2 study of a medicine called xevinapant, which is under investigation as a potential future medicine for people with this type of cancer. WHAT DID THE RESEARCHERS WANT TO FIND OUT?: In this study, researchers wanted to find out whether xevinapant plus chemoradiotherapy could stop the cancer from growing back or getting worse in the years after treatment completion in people with LA SCCHN. They also looked at whether people with this type of cancer had side effects from taking this medicine. Short-term results were collected 18 months after treatment with chemoradiotherapy ended. These results showed that people who received xevinapant plus chemoradiotherapy were less likely to have their cancer grow back, or get worse in the part of the body where it was first found, than people who received liquid placebo-which looked and tasted the same as the active medicine (in this case, xevinapant), but did not contain any medicine-plus chemoradiotherapy. Researchers then continued to collect information for a longer amount of time (at least 3 years). They wanted to see if treatment with xevinapant plus chemoradiotherapy was stopping the cancer from growing back or getting worse and helping people live longer. After this, people were monitored for a further 2 years to see if they were alive 5 years after treatment. WHAT WERE THE MAIN FINDINGS OF THE STUDY?: The results showed that people with this type of cancer who were treated with xevinapant plus chemoradiotherapy were less likely to die, lived longer on average, and were less likely to have their cancer get worse. A phase 3 study, named TrilynX, in a larger group of people, is currently taking place to confirm the results of this study. Clinical Trial Registration: NCT02022098 (Debio 1143-201 Dose-finding and Efficacy Phase I/II Trial) (ClinicalTrials.gov).

Ethical considerations for precision psychiatry: A roadmap for research and clinical practice.

Precision psychiatry is an emerging field with transformative opportunities for mental health. However, the use of clinical prediction models carries unprecedented ethical challenges, which must be addressed before accessing the potential benefits of precision psychiatry. This critical review covers multidisciplinary areas, including psychiatry, ethics, statistics and machine-learning, healthcare and academia, as well as input from people with lived experience of mental disorders, their family, and carers. We aimed to identify core ethical considerations for precision psychiatry and mitigate concerns by designing a roadmap for research and clinical practice. We identified priorities: learning from somatic medicine; identifying precision psychiatry use cases; enhancing transparency and generalizability; fostering implementation; promoting mental health literacy; communicating risk estimates; data protection and privacy; and fostering the equitable distribution of mental health care. We hope this blueprint will advance research and practice and enable people with mental health problems to benefit from precision psychiatry.

Absolute Lymphocyte Count After COVID-19 Vaccination Is Associated with Vaccine-Induced Hypermetabolic Lymph Nodes on 18F-FDG PET/CT: A Focus in Breast Cancer Care.

We aimed to predict the presence of vaccine-induced hypermetabolic lymph nodes (v-HLNs) on 18F-FDG PET/CT after coronavirus disease 2019 (COVID-19) vaccination and determine their association with lymphocyte counts. Methods: In this retrospective single-center study, we included consecutive patients who underwent 18F-FDG PET/CT imaging after messenger RNA- or viral vector-based COVID-19 vaccination between early March and late April 2021. Demographics, clinical parameters, and absolute lymphocyte count (ALC) were collected, and their association with the presence of v-HLNs in the draining territory was studied by logistic regression. Results: In total, 260 patients were eligible, including 209 (80%) women and 145 (56%) with breast cancer. The median age was 50 y (range, 23-96 y). The messenger RNA vaccine had been given to 233 (90%). Ninety (35%) patients had v-HLNs, with a median SUVmax of 3.7 (range, 2.0-26.3), and 74 (44%) displayed lymphopenia, with a median ALC of 1.4 × 109/L (range, 0.3-18.3 × 109/L). An age of no more than 50 y (odds ratio [OR], 2.2; 95% CI, 1.0-4.5), the absence of lymphopenia (OR, 2.2; 95% CI, 1.1-4.3), and less than a 30-d interval from the last vaccine injection to the 18F-FDG PET/CT (OR, 2.6; 95% CI, 1.3-5.6) were independent factors for v-HLNs on multivariate analysis. In breast cancer patients, the absence of lymphopenia was the only independent factor significantly associated with v-HLNs (OR, 2.9; 95% CI, 1.2-7.4). Conclusion: Patients with a normal ALC after COVID-19 vaccination were more likely to have v-HLNs on 18F-FDG PET/CT, both of which might be associated with a stronger immune response to vaccination.