Variation of resection margins in oral cancer in dependence of tumor stage and subsite - a retrospective cohort study.

OBJECTIVES: Surgical resection is a key component of the treatment of head and neck cancer and the achievement of free surgical margins are essential for the patients' outcome in terms of survival. While there is a general recommendation for a free resection range of 5 mm, up to date, there is a lack of investigations on the quality of tumor resection in dependence of affected subsite and tumor stage. In the presented study, predictors for the achieved resection margins in surgically treated oral squamous cell carcinomas were analyzed. MATERIALS AND METHODS: A cohort of 567 patients was included in a retrospective analysis and resection status with exact margin ranges were analysed. Tumor stage, affected subsite and the results of the intraoperative frozen section analysis were assessed. Primary endpoint was the achieved resection margin in mm, secondary endpoints were overall and progression-free survival. RESULTS: The observed mean values of minimal resection margins differed significantly between the investigated subsites (p = 0.042),pathological tumor stages (p < 0.001) and in tumors which demonstrated perineural infiltration (Pn1, p = 0.002). Furthermore, there was a significant impact of the results of the intraoperative frozen section analysis on progression-free and overall survival (p < 0.001). CONCLUSIONS: Our data clearly indicate that resection status differs between tumors of different subsites and tumor stages. CLINICAL RELEVANCE: Clinical procedures should be adapted in order to achieve similar certainty in all resections, and, thus to improve patients' outcome.

Second primary squamous cell carcinoma of the oral cavity - a retrospective cohort study of therapeutic procedures and oncological outcome.

OBJECTIVES: In the presented study, the occurrence rates of second primary oral carcinomas and their prognostic relevance were analyzed. MATERIALS AND METHODS: All patients with surgically treated oral squamous cell carcinomas within the years 2010 and 2022 in our department were included in this retrospective cohort study. Two groups were designed including patients with second primary carcinomas and patients with local tumor recurrences. Occurrence rates, tumor stages and applied therapies were assessed. Primary outcome was overall survival in dependence of the index tumor. Secondary outcomes were overall survival in dependence of local recurrences or second primary tumors. RESULTS: An overall number of 908 patients was included in the analysis. 98 patients (10.8%) developed a second primary oral squamous cell carcinoma. Patients with second primary tumors presented significantly (p < 0.001) better overall survival in dependence of the index tumor compared to patients suffering from local recurrences. There was no significant difference in overall survival (p = 0.4) in dependence of the date of second primary tumor or local recurrence. Patients with second primary tumors were more likely to receive surgery-based therapy compared to patients with local recurrences who more frequently received definitive radiotherapy. CONCLUSION: Our data indicates different clinical courses in terms of therapy and survival of patients suffering from second primary tumors compared to patients with local tumor recurrences. This may be due to a more aggressive biology of local recurrences and earlier detection of second primaries due to oncological follow-up of the index tumor. CLINICAL RELEVANCE: The differentiation of local tumor recurrences and second primary tumors is of clinical relevance, as applicable therapies and resulting prognosis may differ significantly.

Combined Photon and Carbon Ion Radiation Therapy for Sinonasal Malignancies: Results of the HIT-SNT Prospective Phase 2 Trial.

PURPOSE: Radiation treatment of sinonasal malignancies is a challenging task due to proximity to critical structures of the head and neck and skull base. Local tumor control is highly dose-dependent, but dose application is limited due to accompanying toxicity and dose constraints. To evaluate the toxicity and efficacy of combined radiation treatment with intensity-modulated radiation therapy (IMRT) and carbon ion boost, we conducted a prospective phase 2 IMRT-Heidelberg Ion-Beam Therapy Sinonasal Tumors (HIT-SNT) trial. METHODS AND MATERIALS: Between 2011 and 2019, we treated 35 patients with histologically proven, incompletely resected or inoperable adeno- (51%) or squamous cell carcinoma (49%) of the paranasal sinuses with combined IMRT (50 Gy) and carbon ion boost (24 Gy relative biologic effectiveness) to a total dose of 74 Gy. RESULTS: Acute mucositis Common Terminology Criteria for Adverse Events (CTCAE) grade 3 occurred in 12% of patients (n = 4) and was accompanied by odynophagia CTCAE grade 3. Except for 1 case of grade 3 weight loss, no other acute high-grade toxicity (grade 3-4) was observed. In a small patient cohort of 15 patients eligible for long-term follow-up we have seen no high-grade (grade ≥3) long-term side effects 2 years after radiation therapy. None of these patients suffered from therapy-associated vision or hearing loss. Secondary endpoints were 2-year overall survival, 2-year local progression-free survival, 2-year progression-free survival, and 2-year metastases-free survival with 79.4%, 61.8%, 61.8%, and 64.8%, respectively. CONCLUSIONS: To our knowledge, this is the first prospective data on toxicity and outcome of bimodal radiation therapy for the rare entity of sinonasal malignancies. Our study shows a low rate of CTCAE-reported acute toxicity with reasonable tumor control and survival rates after bimodal radiation therapy, which therefore remains a therapy approach to be further evaluated.

HLA-E and Its Soluble Form as Indicators of a Sex-Specific Immune Response in Patients with Oral Squamous Cell Carcinoma.

The human leukocyte antigene E (HLA-E) is associated with tumorigenesis in various cancers. Immunoncology along with sex-specific aspects in cancer therapy are now in scientific focus. Therefore, immunohistochemical HLA-E expression was retrospectively analysed in a cohort of oral squamous cell carcinomas (OSCC) after surgical therapy. Then, serum concentration of HLA-E (sHLA-E) was quantified in a prospective cohort by enzyme-linked immunosorbent assay. High HLA-E expression was associated with advanced UICC stage (Spearman's correlation: p = 0.002) and worse survival (Cox-regression: progression-free survival: hazard ratio (HR) 3.129, confidence range (CI) 1.443-6.787, p = 0.004; overall survival: HR 2.328, CI 1.071-5.060, p = 0.033). The sHLA-E concentration was significantly higher in the control group than in tumor group (Mann-Whitney U-test (MW-U): p = 0.021). Within the tumor group, women showed significantly higher sHLA-E levels than men (MW-U: p = 0.049). A closer look at the tumor group and the control group showed that gender-specific differences exist: while no differences in sHLA-E concentration were detectable between female subjects of tumor group and control group (MW-U: p = 0.916), male subjects of tumor group had a significantly lower sHLA-E concentration compared to those of control group (MW-U: p = 0.001). In summary, our results provide evidence for sex-specific differences in immune responses in OSCC. This fact should be considered regarding future immunotherapy regimens.

The Use of Artificial Intelligence for the Classification of Craniofacial Deformities.

Positional cranial deformities are a common finding in toddlers, yet differentiation from craniosynostosis can be challenging. The aim of this study was to train convolutional neural networks (CNNs) to classify craniofacial deformities based on 2D images generated using photogrammetry as a radiation-free imaging technique. A total of 487 patients with photogrammetry scans were included in this retrospective cohort study: children with craniosynostosis (n = 227), positional deformities (n = 206), and healthy children (n = 54). Three two-dimensional images were extracted from each photogrammetry scan. The datasets were divided into training, validation, and test sets. During the training, fine-tuned ResNet-152s were utilized. The performance was quantified using tenfold cross-validation. For the detection of craniosynostosis, sensitivity was at 0.94 with a specificity of 0.85. Regarding the differentiation of the five existing classes (trigonocephaly, scaphocephaly, positional plagiocephaly left, positional plagiocephaly right, and healthy), sensitivity ranged from 0.45 (positional plagiocephaly left) to 0.95 (scaphocephaly) and specificity ranged from 0.87 (positional plagiocephaly right) to 0.97 (scaphocephaly). We present a CNN-based approach to classify craniofacial deformities on two-dimensional images with promising results. A larger dataset would be required to identify rarer forms of craniosynostosis as well. The chosen 2D approach enables future applications for digital cameras or smartphones.

Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma.

The introduction of immune checkpoint inhibition for recurrent and metastatic head and neck cancer has brought a new treatment option for patients suffering from advanced oral cancers without a chance for curation using surgery or radiotherapy. The application of immune checkpoint inhibitors in most cases is based on the expression levels of PD-L1 in the tumor tissue. To date, there is a lack of data on the dynamic regulation of PD-L1 during disease progression. Therefore, this study aimed to evaluate the expression levels of PD-L1 in a large cohort of patients (n = 222) with oral squamous cell carcinoma including primary and recurrent tumors. Semiautomatic digital pathology scoring was used for the assessment of PD-L1 expression levels in primary and recurrent oral squamous cell carcinoma. Survival analysis was performed to evaluate the prognostic significance of the protein expression at different stages of the disease. We found a significant up-regulation of PD-L1 expression from primary disease to recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1 ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In several cases, a shift from low PD-L1 expression in primary tumors to high PD-L1 expression in recurrent tumors was identified. Multivariate Cox regression analysis did not reveal a significantly higher risk of death (p = 0.078) or recurrence (p = 0.926) in patients with higher PD-L1 expression. Our findings indicate that the exclusive analysis of primary tumor tissue prior to the application of checkpoint blockade may lead to the misjudgment of PD-L1 expression in recurrent tumors.

Comparison of Antero-Lateral Thigh Flap and Vastus Lateralis Muscle Flap for the Treatment of Extensive Scalp Defects-A Retrospective Cohort Study.

Free flap reconstruction is the standard of care for extensive defects of the head and neck area. In this study, two types of free flaps, the antero-lateral thigh flap (ALT) and the vastus lateralis muscle flap, were compared. The primary endpoint was flap success, secondary endpoints were complication rates, hospitalization and surgery time. Cases with defect situations of the scalp and consecutive microvascular free flap reconstructions using either ALT flaps or vastus lateralis muscle flaps between 2014 and 2022 were retrospectively analyzed. Indications, perioperative handling and outcomes were compared. Twenty patients were included in the analysis. Ten patients (50%) received a free flap reconstruction using an ALT flap and ten patients (50%) received a vastus lateralis flap. A simultaneous two-team approach was possible in each case and the flap success rate was 100% with the need for one successful anastomosis revision. The mean defect size in our cohort was 147 ± 46 cm2. There were no significant differences in surgery time, duration of hospitalization or complication rate between both cohorts. Both free flaps, the ALT and the vastus lateralis flap, are suitable for the closure of large scalp defects. They provide high success rates, short surgery times without the need for patient repositioning and low donor-site morbidity. The vastus lateralis muscle flap bares the advantage of being perforator-independent and allows for the preparation of long vessels for anastomosis if needed while baring the disadvantage of a prolonged period of healing via granulation or the need for secondary surgery in terms of covering by split-thickness skin grafts which may interfere with necessary adjuvant treatment in oncological patients.

Impact of Salvage Surgery on Health-Related Quality of Life in Oral Squamous Cell Carcinoma: A Prospective Multi-Center Study.

BACKGROUND: Patients with recurrent oral squamous cell carcinoma (OSCC) have limited treatment options. Salvage surgery offers potential curative therapy. The need for extensive ablative surgery together with microvascular reconstruction implies invasive and painful treatment with questionable functional outcome. To address the impact of salvage surgery on the health-related quality of life (HRQoL) of patients suffering from recurrent OSCC, a multi-center prospective analysis was initiated. MATERIAL AND METHODS: Patients with recurrent OSCC from 2015 to 2022 at two German cancer centers were included. Interdisciplinary tumor board decisions determined surgery as the only curative treatment modality. HRQoL, was assessed via a EORTC questionnaire (European Organization for Research and Treatment of Cancer-EORTC: QLQ-C30 and QLQ-H&N35) in dependence of the recurrent tumor stage. Patients completed the questionnaires once before surgery (baseline) and then every 3 months during follow-up or up to the end of treatment. RESULTS: In total, 55 patients were included. The mean follow-up period was 26.7 ± 19.3 months. Global health status showed superior mean scores after 12 months (60.83 ± 22.58) compared to baseline (53.33 ± 26.41) in stage 1 and 2 recurrent tumors. In advanced recurrent tumors' mean scores for global health showed only minor positive differences after 12 months (55.13 ± 22.7) compared to baseline (53.2 ± 25.58). In terms of the mouth pain, mean scores were lower after salvage surgery in small recurrent tumors after 12 months (20.37 ± 17.73) compared to baseline (41.67 ± 33.07; Wilcoxon two-sample signed-rank test p = 0.028). In advanced recurrent tumors, a significant reduction in mean scores was detected 3 months after salvage surgery (29.7 ± 22.94) compared to baseline (47.76 ± 25.77; Wilcoxon two-sample signed-rank test p = 0.003). Up to 12 months, swallowing function was evaluated inferior compared to baseline independent of tumor stage (Mean score recurrent stage I/II: 12-months 48.15 ± 27.57, baseline 28.7 ± 22.87; stage III/IV: 12-months 49.36.42 ± 27.53; baseline 30.13 ± 26.25). CONCLUSION: Improved HRQoL could be obtained in advanced recurrent OSCC after salvage surgery despite reduced swallowing function. In small recurrent tumors, overall, HRQoL was superior to baseline. Salvage surgery positively affected pain burden. For advanced recurrent tumors, important pain relieve could be observed as soon as 3 months after surgery.

Accuracy of Patient-Specific Implants in Virtually Planned Segmental Le Fort I Osteotomies.

(1) Background: In orthognathic surgery, segmental Le Fort I osteotomies are a valuable method to correct maxillary deformities or transversal discrepancies. However, these procedures are technically challenging, and osteosynthesis can be prone to error. (2) Methods: In this retrospective, monocentric cohort study, patients were enrolled who underwent a virtually planned segmental maxillary osteotomy during their combined treatment. Positioning and osteosynthesis were achieved by either a 3D-printed splint and conventional miniplates or patient-specific implants (PSI). The preoperative CT data, virtual planning data, and postoperative CBCT data were segmented. The deviation of all the segments from the desired virtually planned position was measured using the analysis function of IPS CaseDesigner. (3) Results: 28 Patients in the PSI Group and 22 in the conventional groups were included. The PSI group showed significantly lower deviation from the planned position anteroposteriorly (-0.63 ± 1.62 mm vs. -1.3 ± 2.54 mm) and craniocaudally (-1.39 ± 1.59 mm vs. -2.7 ± 3.1 mm). For rotational deviations, the pitch (0.64 ± 2.59° vs. 2.91 ± 4.08°), as well as the inward rotation of the lateral segments, was positively influenced by PSI. (4). Conclusions: The presented data show that patient-specific osteosynthesis significantly reduces deviations from the preoperative plan in virtually planned cases. Transversal expansions and vertical positioning can be addressed better.

Surgical Treatment of Carcinomas of the Oral Minor Salivary Glands-Oncological Outcome in Dependence of Tumor Entity and Therapeutic Strategies.

The aim of this study was to analyze the clinical outcomes of three types of minor salivary gland carcinomas (adenoid-cystic carcinomas (ACC), adeno carcinomas not otherwise specified (AC-NOS), and mucoepidermoid carcinomas (MEC)) after primary surgical therapy. A retrospective cohort study was designed and patients with cancer of the minor oral salivary glands treated in our department in the years 2011 to 2022 were included. Clinicopathological data were evaluated to compare overall survival and progression-free survival between the entities. Eighty-one patients were included. The rates of cervical metastases were 38.9% for ACC, 25% for MEC, and 9.1% for AC-NOS. ACC exhibited significantly higher rates of local and systemic disease recurrence (p = 0.02), and the presence of neck node metastases was confirmed as an independent prognostic factor for progression-free survival (p = 0.014). Treatment success in terms of oncological outcome varied significantly between the different entities and implies different treatment regimens for each tumor entity.

Free-Flap Reconstruction in Early-Stage Squamous Cell Carcinoma of the Oral Cavity-A Prospective Monocentric Trial to Evaluate Oncological Outcome and Quality of Life.

Surgery is generally accepted as standard treatment in oral cancer, but the reconstructive procedures remain a matter of debate. The aim of this study was to evaluate oncological outcome and quality of life following surgical resection and free-flap reconstruction in patients with early oral squamous cell carcinoma. The presented trial was performed as a prospective, single-center observation study. Inclusion criteria were primary surgery in early-stage oral squamous cell carcinoma with free-flap reconstruction. Endpoints were overall and progression-free survival and quality of life up to 24 months after surgery. Twenty-six patients were included. Overall survival was 100% and progression-free survival was 92.3% in a maximum follow-up time of 21 months. Global quality of life showed no significant alteration after surgery. Patients reported a significant reduction in pain (p = 0.048) and a decreasing impairment of speech one year after surgery (p = 0.021). Free-flap reconstruction is a safe procedure that results in excellent oncological outcome and quality of life. Functional outcome is of high relevance in early-stage tumors of the head and neck and may mostly be affected by reconstructive procedures. Therefore, a prospective evaluation to explore success and the effects of surgical therapy is highly warranted.

Automated calculation of ontology-based planning proposals: An application in reconstructive oral and maxillofacial surgery.

BACKGROUND: Structured modelling of surgical knowledge and its automated processing is still challenging. The aim of this work is to introduce a novel approach for automated calculation of ontology-based planning proposals in mandibular reconstruction and conduct a feasibility study. METHODS: The presented approach is composed of an RDF(S) ontology, a 3D mandible template and a calculator-optimiser algorithm to automatically calculate reconstruction proposals with fibula grafts. To validate the viability of the approach, a feasibility study was conducted on 164 simulated mandibular reconstructions. RESULTS: The ontology defines 244 different reconstruction variants and 80 analyses for optimization. In 146 simulated cases, a proposal could be automatically calculated (average time 8.79 ± 4.03 s). The assessments of the proposals by three clinical experts indicate the viability of the approach. CONCLUSIONS: Due to the modular separation between computational logic and domain knowledge, the developed concepts can be easily maintained, reused and adapted for other applications.

3D-2D Distance Maps Conversion Enhances Classification of Craniosynostosis.

OBJECTIVE: Diagnosis of craniosynostosis using photogrammetric 3D surface scans is a promising radiation-free alternative to traditional computed tomography. We propose a 3D surface scan to 2D distance map conversion enabling the usage of the first convolutional neural networks (CNNs)-based classification of craniosynostosis. Benefits of using 2D images include preserving patient anonymity, enabling data augmentation during training, and a strong under-sampling of the 3D surface with good classification performance. METHODS: The proposed distance maps sample 2D images from 3D surface scans using a coordinate transformation, ray casting, and distance extraction. We introduce a CNN-based classification pipeline and compare our classifier to alternative approaches on a dataset of 496 patients. We investigate into low-resolution sampling, data augmentation, and attribution mapping. RESULTS: Resnet18 outperformed alternative classifiers on our dataset with an F1-score of 0.964 and an accuracy of 98.4%. Data augmentation on 2D distance maps increased performance for all classifiers. Under-sampling allowed 256-fold computation reduction during ray casting while retaining an F1-score of 0.92. Attribution maps showed high amplitudes on the frontal head. CONCLUSION: We demonstrated a versatile mapping approach to extract a 2D distance map from the 3D head geometry increasing classification performance, enabling data augmentation during training on 2D distance maps, and the usage of CNNs. We found that low-resolution images were sufficient for a good classification performance. SIGNIFICANCE: Photogrammetric surface scans are a suitable craniosynostosis diagnosis tool for clinical practice. Domain transfer to computed tomography seems likely and can further contribute to reducing ionizing radiation exposure for infants.

Oral Sequelae after Head and Neck Radiotherapy: RCT Comparing 3D-Printed Tissue Retraction Devices with Conventional Dental Splints.

OBJECTIVES: To evaluate oral sequelae after head and neck radiotherapy (RT) when using two different types of intraoral appliances. Thermoplastic dental splints (active control) protect against backscattered radiation from dental structures. Semi-individualized, 3D-printed tissue retraction devices (TRDs, study group) additionally spare healthy tissue from irradiation. MATERIALS AND METHODS: A total of 29 patients with head and neck cancer were enrolled in a randomized controlled pilot trial and allocated to receive TRDs (n = 15) or conventional splints (n = 14). Saliva quality and quantity (Saliva-Check, GC), taste perception (Taste strips, Burghart-Messtechnik), and oral disability (JFLS-8, OHIP-14, maximum mouth opening) were recorded before and 3 months after RT start. Radiotherapy target volume, modality, total dose, fractionation, and imaging guidance were case-dependent. To evaluate intra-group developments between baseline and follow-up, nonparametric Wilcoxon tests were performed. Mann-Whitney-U tests were applied for inter-group comparisons. RESULTS: At follow-up, taste perception was unimpaired (median difference in the total score; TRDs: 0, control: 0). No significant changes were found regarding oral disability. Saliva quantity (stimulated flow) was significantly reduced with conventional splints (median -4 mL, p = 0.016), while it decreased insignificantly with TRDs (median -2 mL, p = 0.07). Follow-up was attended by 9/15 study group participants (control 13/14). Inter-group comparisons showed no significant differences but a tendency towards a better outcome for disability and saliva quality in the intervention group. CONCLUSION: Due to the small cohort size and the heterogeneity of the sample, the results must be interpreted with reservation. Further research must confirm the positive trends of TRD application. Negative side-effects of TRD application seem improbable.

Infants With Trigonocephaly Treated With Fronto-Orbital Remodelling and Endocortical Positioning of Resorbable Plates-A Retrospective Cohort Study Including 101 Patients.

PURPOSE: Fronto-orbital remodeling is the gold standard for surgical treatment of metopic synostosis in many craniofacial centers. For fixation, resorbable materials are widely used. Because of swelling during resorption, the positioning of the plates can be relevant. Therefore, the goal of this study was to investigate whether there are limitations to endocortical positioning of resorbable plates. METHODS: In this retrospective study, all patients with metopic craniosynostosis resulting in trigonocephaly, who were treated with a standardized fronto-orbital remodeling and endocortical positioning of resorbable plates, between February 2012 and December 2019 were included. The endpoint of this study was the postoperative complications that can be attributed to the material used. RESULTS: A total of 101 patients, who were treated at our unit, could be included with a male predominance, 81 (80.2%) boys versus 20 (19.8%) girls. Surgery was performed at a median age of 9 months (±2.56). No complications were seen related to resorbable plates. All patients of our study population were categorized as Whitaker classification I and II. CONCLUSION: This study shows that the risk level in using endocortical resorbable plates positioned on the inner surface of the bone is low. From an aesthetic point of view, we could not detect any disadvantage.

The value of prebent reconstruction plates and in-house 3D printing.

INTRODUCTION: Reconstruction plates, prebent on 3D printed models, are a cheap, quick, and safe solution to improve mandibular reconstruction procedures. The European Medical Device Regulation has changed recently and severely affects 3D printing in hospitals. Therefore, its legitimation must be discussed. This retrospective observational Case-Control Study aimed to evaluate the impact of prebent reconstruction plates on the condylar position in the temporomandibular joint after continuity resection of the mandible in oncological cases. MATERIALS AND METHODS: We included patients who underwent segmental mandibular resection without exarticulation of the condyle or history of prior surgery. The patients were divided into groups with prebent plates on a stereolithographic model and intraoperatively bent reconstruction plates. The segmental defects were categorized using the Jewer Classification. Computed Tomography (CT) scans before and after surgery were analyzed using a standardized method to measure the metric movement of the condyles, as well as their angulation to reference planes to quantify positional changes (primary outcome measures). The influence of the defect location, according to the Jewer classification, was evaluated as a secondary outcome measure. RESULTS: 73 patients, including 33 with preformed reconstruction plates, were included. We could show significantly fewer rotational deviations in cases of prefabricated osteosynthesis in the coronal plane (p<0,001) and in the sagittal plane (p<0,027). DISCUSSION: Using preformed reconstruction plates on 3D printed models improves the correct anatomical position of the condyle after mandibular resection. Especially Jewer-class-L defects seem to benefit from individualized reconstruction plates.

Diagnostic accuracy comparing OPT and CBCT in the detection of non-vital bone changes before tooth extractions in patients with antiresorptive intake.

OBJECTIVES: To compare the diagnostic accuracy in detecting early non-vital bone changes between orthopantomography (OPT) and cone-beam computed tomography (CBCT) in correlation with histopathological findings before tooth extractions in patients with antiresorptive (AR) intake. SUBJECTS: Patients with an indication tooth extraction who had received OPT and CBCT preoperatively while or after undergoing AR treatment were prospectively enrolled over a 24-month period in the progesterone in spontaneous miscarriage (PRISM) trial. Imaging studies were randomly analyzed by three examiners for early non-vital bone changes using specific predefined characteristics and a 5-level scale (1 definite absence of criteria to 5 definite presence of criteria). Sensitivity and specificity values were calculated in correlation with the histopathologically evaluated bone samples at the time point of tooth extraction. RESULTS: One hundred thirty patients with 237 treated extraction sites met the inclusion criteria. For all images evaluated by all examiners, CBCT (430/492; 87.4%; receiver operating characteristic [ROC]: area under the curve [AUC] = 0.88; p < 0.001) was more likely to detect histopathologically confirmed non-vital bone than the OPT (132/492; 26.8%; ROC: AUC = 0.562; p = 0.115). CONCLUSIONS: In the detection of non-vital bone changes, CBCT is superior to OPT in both sensitivity and specificity. Specific imaging characteristics allow for the prediction of early non-vital bone changes already at the time before tooth extractions.

IDO1 is highly expressed in macrophages of patients in advanced tumour stages of oral squamous cell carcinoma.

PURPOSE: Strategies for Indolamine-2,3-dioxygenase 1 (IDO1) inhibition in cancer immunotherapy once produced encouraging results, but failed in clinical trials. Recent evidence indicates that immune cells in the tumour microenvironment, especially macrophages, contribute to immune dysregulation and therefore might play a critical role in drug resistance. METHODS: In this study, we investigated the significance of IDO1 expressing immune cells in primary tumours and corresponding lymph node metastases (LNMs) in oral squamous cell carcinoma (OSCC) by immunohistochemistry. The link between IDO1 and macrophages was investigated by flow cytometry in tumour tissue, healthy adjacent tissue and peripheral blood mononuclear cells (PBMCs). IDO1 activity (measured as Kynurenine/Tryptophan ratio) was assessed by ELISAs. RESULTS: High IDO1 expression in tumour-infiltrating immune cells was significantly correlated with advanced stages [Spearman's rank correlation (SRC), p = 0.027] and reduced progression-free survival (multivariate Cox regression, p = 0.034). IDO1 was significantly higher expressed in PBMCs of patients in advanced stages than in healthy controls (ANOVA, p < 0.05) and IDO1+ macrophages were more abundant in intratumoural areas than peritumoural (t test, p < 0.001). IDO1 expression in PBMCs was significantly correlated with IDO1 activity in serum (SRC, p < 0.05). IDO1 activity was significantly higher in patients with LNMs (t test, p < 0.01). CONCLUSION: All in all, IDO1 expressing immune cells, especially macrophages, are more abundant in advanced stages of OSCC and are associated with reduced progression-free survival. Further investigations are needed to explore their role in local and systemic immune response. The IDO1 activity might be a suitable biomarker of metastasis in OSCC patients.

Impact of data synthesis strategies for the classification of craniosynostosis.

Introduction: Photogrammetric surface scans provide a radiation-free option to assess and classify craniosynostosis. Due to the low prevalence of craniosynostosis and high patient restrictions, clinical data are rare. Synthetic data could support or even replace clinical data for the classification of craniosynostosis, but this has never been studied systematically. Methods: We tested the combinations of three different synthetic data sources: a statistical shape model (SSM), a generative adversarial network (GAN), and image-based principal component analysis for a convolutional neural network (CNN)-based classification of craniosynostosis. The CNN is trained only on synthetic data but is validated and tested on clinical data. Results: The combination of an SSM and a GAN achieved an accuracy of 0.960 and an F1 score of 0.928 on the unseen test set. The difference to training on clinical data was smaller than 0.01. Including a second image modality improved classification performance for all data sources. Conclusions: Without a single clinical training sample, a CNN was able to classify head deformities with similar accuracy as if it was trained on clinical data. Using multiple data sources was key for a good classification based on synthetic data alone. Synthetic data might play an important future role in the assessment of craniosynostosis.