CD4+ T cell activation distinguishes response to anti-PD-L1+anti-CTLA4 therapy from anti-PD-L1 monotherapy.

Cancer patients often receive a combination of antibodies targeting programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA4). We conducted a window-of-opportunity study in head and neck squamous cell carcinoma (HNSCC) to examine the contribution of anti-CTLA4 to anti-PD-L1 therapy. Single-cell profiling of on- versus pre-treatment biopsies identified T cell expansion as an early response marker. In tumors, anti-PD-L1 triggered the expansion of mostly CD8+ T cells, whereas combination therapy expanded both CD4+ and CD8+ T cells. Such CD4+ T cells exhibited an activated T helper 1 (Th1) phenotype. CD4+ and CD8+ T cells co-localized with and were surrounded by dendritic cells expressing T cell homing factors or antibody-producing plasma cells. T cell receptor tracing suggests that anti-CTLA4, but not anti-PD-L1, triggers the trafficking of CD4+ naive/central-memory T cells from tumor-draining lymph nodes (tdLNs), via blood, to the tumor wherein T cells acquire a Th1 phenotype. Thus, CD4+ T cell activation and recruitment from tdLNs are hallmarks of early response to anti-PD-L1 plus anti-CTLA4 in HNSCC.

Bridging the knowledge-Practice gap: Insights from a survey of Belgian dental professionals on diagnosis and supportive oral cancer treatment in comparison with international guidelines.

OBJECTIVE: Early detection significantly improves the prognosis of oral cancer patients, contingent upon the knowledge of dental professionals. This study aimed to assess and compare the knowledge, practices and perceptions regarding oral cancer among dental professionals in Belgium. MATERIALS AND METHODS: A cross-sectional survey was distributed via Qualtrics to general dentists, dental specialists, dental hygienists, and oral and maxillofacial surgeons. The self-administered questionnaire comprised three sections: demographics (4 questions), knowledge (9 questions) and clinical practices (19 questions) related to oral cancer detection and treatment. Descriptive statistics were employed for data analysis, with Chi-square tests assessing responses by specialization, gender, years of experience and number of oral cancer patients treated. RESULTS: A total of 262 questionnaires were completed, with the majority of respondents being general dentists (61%) followed by dental specialists (25%), oral hygienists (8%) and oral and maxillofacial surgeons (6%). 70% of the respondents reported treating fewer than four oral cancer patients throughout their careers. 5 out of the 9 knowledge questions achieved over 50% correct responses, with an average correct answer rate of 54%. Oral and maxillofacial surgeons and dental professionals who have treated more than four oral cancer patients, demonstrated significantly higher scores on multiple knowledge questions. Responses to clinically oriented questions showed less diversity across professions, and generally aligning with guidelines from professional oncological societies. CONCLUSION: This survey highlights the need for enhanced education on oral cancer among Belgian dental professionals. Knowledge levels were notably higher among more experienced respondents. The development and implementation of comprehensive guidelines tailored to dentists and oral hygienists for oral cancer prevention and patient care are warranted to optimize clinical practice standards.

Virtual reconstruction of orbital defects using Gaussian process morphable models.

PURPOSE: The conventional method to reconstruct the bone level for orbital defects, which is based on mirroring and manual adaptation, is time-consuming and the accuracy highly depends on the expertise of the clinical engineer. The aim of this study is to propose and evaluate an automated reconstruction method utilizing a Gaussian process morphable model (GPMM). METHODS: Sixty-five Computed Tomography (CT) scans of healthy midfaces were used to create a GPMM that can model shape variations of the orbital region. Parameter optimization was performed by evaluating several quantitative metrics inspired on the shape modeling literature, e.g. generalization and specificity. The reconstruction error was estimated by reconstructing artificial defects created in orbits from fifteen CT scans that were not included in the GPMM. The developed algorithms utilize the existing framework of Gaussian process morphable models, as implemented in the Scalismo software. RESULTS: By evaluating the proposed quality metrics, adequate parameters are chosen for non-rigid registration and reconstruction. The resulting median reconstruction error using the GPMM was lower (0.35 ± 0.16 mm) compared to the mirroring method (0.52 ± 0.18 mm). In addition, the GPMM-based reconstruction is automated and can be applied to large bilateral defects with a median reconstruction error of 0.39 ± 0.11 mm. CONCLUSION: The GPMM-based reconstruction proves to be less time-consuming and more accurate than reconstruction by mirroring. Further validation through clinical studies on patients with orbital defects is warranted. Nevertheless, the results underscore the potential of GPMM-based reconstruction as a promising alternative for designing patient-specific implants.

Surgical management of a temporal meningoencephalocele with a patient-specific combined craniofossa prosthesis: illustrative case.

BACKGROUND: Meningoencephaloceles can originate through any defect in the cranial bones, including the skull base. They can be completely asymptomatic or present with typical symptoms such as headaches, seizures, or meningitis. OBSERVATIONS: The authors present the case of a 54-year-old female who presented with right-sided ear and temporomandibular joint (TMJ) pain. Computed tomography showed a large lytic lesion of the squamous part of the temporal bone with cortical bone destruction, extending to the mandibular fossa. Magnetic resonance imaging demonstrated a temporal bone meningoencephalocele. The patient underwent resection, dural repair, and multilayer reconstruction with a patient-specific three-dimensional-printed titanium combined craniofossa prosthesis. LESSONS: To the authors' knowledge, this is the first case report of TMJ pain associated with a temporal meningoencephalocele. The exact location and extension of the lesion determine the surgical approach and need for reconstruction in temporal bone meningoencephaloceles. In cases of destruction of the mandibular fossa, a patient-specific combined craniofossa prosthesis is recommended to reconstruct the bone defect. https://thejns.org/doi/10.3171/CASE24132.

OrthoCalc: The six degrees of freedom measurement workflow of rotational and displacement changes for maxilla positioning evaluation.

BACKGROUND: This study is undertaken to establish the accuracy and reliability of OrthoCalc, a 3D application designed for the evaluation of maxillary positioning. METHODS: We registered target virtual planned models, maxillary models from pre-operative and post-operative CT scans, and post-operative intra-oral scans to a common reference system, allowing for digital evaluation. To assess rotational changes, we introduced a novel measurement method based on virtual cuboid models. Displacement errors were calculated based on proposed registration matrices. We also compared OrthoCalc to established commercial medical software as a benchmark. RESULTS: Statistical significance calculated showed no significant differences between OrthoCalc and commercial software. the biggest error of 0.04 degree in rotation change was found in the yaw. A maximum displacement change of 0.75 mm was found in the X direction. CONCLUSIONS: Our study validates OrthoCalc as a precise and reliable tool for assessing maxillary position changes with six degrees of freedom in orthognathic surgery, endorsing its clinical utility.

Exploring long-term responses to immune checkpoint inhibitors in recurrent and metastatic head and neck squamous cell carcinoma.

OBJECTIVES: Immune checkpoint inhibitors (ICI) have introduced a new era in the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Optimal duration for ICI therapy is still unclear and the long-term outcomes and toxicity in patients responding to these therapies warrant further exploration. This study attempts to identify the clinical and biological determinants of a durable response and evaluate outcomes following ICI treatment discontinuation. MATERIALS AND METHODS: A retrospective review of 181 patients treated with ICI for R/M HNSCC was conducted. Long-term responders were defined as patients who sustained disease control at least two years after initiating ICI therapy. We compared clinical and biological characteristics associated with these long-term responders against the broader treatment population. RESULTS: 10 % of R/M HNSCC patients treated with ICIs demonstrated a durable long-term response. Only three relapses (16 %) occurred after discontinuing ICI treatment in this subset, with a median follow-up of 52 months. Upon retreatment with ICI, two attained a documented response. Extended ICI response was observed even with < 2 years of treatment. 74 % of long-term responders experienced immune-related adverse events (irAEs), 37 % of which severe irAEs. Hypothyroidism was the most frequently reported irAEs. The predictive potential of systemic inflammation indices for clinical response appears to be limited. CONCLUSIONS: ICI present an optimistic avenue for HNSCC patients, offering substantial long-term responses. The study suggests that a two-year treatment could be optimal and irAEs, although common, are typically mild.