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Purpose: [64Cu]Cu-DOTA-AE105 urokinase-type plasminogen activator receptor (uPAR)-PET/CT is a novel and promising imaging modality for cancer visualization, although it has not been tested in head and neck cancer patients nor in preclinical models that closely resemble these heterogenous tumors, i.e., patient-derived xenograft (PDX) models. The aim of the present study was to establish and validate oral squamous cell carcinoma (OSCC) PDX models and to evaluate [64Cu]Cu-uPAR-PET/CT for tumor imaging in these models. Procedures: PDX flank tumor models were established by engrafting tumor tissue from three patients with locally advanced OSCC into immunodeficient mice. [64Cu]Cu-DOTA-AE105 was injected in passage 2 (P2) mice, and [64Cu]Cu-uPAR-PET/CT was performed 1 h and 24 h after injection. After the last PET scan, all animals were euthanized, and tumors dissected for autoradiography and immunohistochemical (IHC) staining. Results: Three PDX models were established, and all of them showed histological stability and unchanged heterogenicity, uPAR expression, and Ki67 expression through passages. A significant correlation between uPAR expression and tumor growth was found. All tumors of all models (n=29) showed tumor uptake of [64Cu]Cu-DOTA-AE105. There was a clear visual concordance between the distribution of uPAR expression (IHC) and [64Cu]Cu-DOTA-AE105 uptake pattern in tumor tissue (autoradiography). No significant correlation was found between IHC (H-score) and PET-signal (SUVmax) (r=0.34; p=0.07). Conclusions: OSCC PDX models in early passages histologically mimic donor tumors and could serve as a valuable platform for the development of uPAR-targeted imaging and therapeutic modalities. Furthermore, [64Cu]Cu-uPAR-PET/CT showed target- and tumor-specific uptake in OSCC PDX models demonstrating the diagnostic potential of this modality for OSCC patients. [ABSTRACT FROM AUTHOR]

Purpose: The purpose was to investigate the diagnostic performance of bimodal optical and radio-guided sentinel node biopsy (SNB) for oral squamous cell carcinoma (OSCC) sub-sites in the anterior oral cavity. Methods: Prospective study of 50 consecutive patients with cN0 OSCC scheduled for SNB was injected with the tracer complex Tc99m:ICG:Nacocoll. A near-infrared camera was applied for optical SN detection. Endpoints were modality for intraoperative SN detection and false omission rate at follow-up. Results: In all patients, a SN could be detected. In 12/50 (24%) of cases, the SPECT/CT showed no focus in level 1, but intraoperatively a SN in level 1 was optically detected. In 22/50 cases (44%), an additional SN was identified only due to the optical imaging. At follow-up, the false omission rate was 0%. Conclusion: Optical imaging appears to be an effective tool to allow real-time SN identification comprising level 1 unaffected by possible interference of radiation site from the injection. [ABSTRACT FROM AUTHOR]

No clinically approved tumor-specific imaging agents for head and neck cancer are currently available. The identification of biomarkers with a high and homogenous expression in tumor tissue and minimal expression in normal tissue is essential for the development of new molecular imaging targets in head and neck cancer. We investigated the expression of nine imaging targets in both primary tumor and matched metastatic tissue of 41 patients with oral squamous cell carcinoma (OSCC) to assess their potential as targets for molecular imaging. The intensity, proportion, and homogeneity in the tumor and the reaction in neighboring non-cancerous tissue was scored. The intensity and proportion were multiplied to obtain a total immunohistochemical (IHC) score ranging from 0–12. The mean intensity in the tumor tissue and normal epithelium were compared. The expression rate was high for the urokinase-type plasminogen activator receptor (uPAR) (97%), integrin αvβ6 (97%), and tissue factor (86%) with a median total immunostaining score (interquartile range) for primary tumors of 6 (6–9), 12 (12–12), and 6 (2.5–7.5), respectively. For the uPAR and tissue factor, the mean staining intensity score was significantly higher in tumors compared to normal epithelium. The uPAR, integrin αvβ6, and tissue factor are promising imaging targets for OSCC primary tumors, lymph node metastases, and recurrences. [ABSTRACT FROM AUTHOR]

Background: Comorbidity is presumed to impact survival of head and neck squamous cell cancer (HNSCC) patients. However, the prevalence and prognostic impact of comorbidity in these patients is not yet well established. The aim of this study is to outline the comorbidity burden of HNSCC patients and investigate the relation to overall survival and cancer-specific mortality. Methods: The comorbidity burden of patients registered with HNSCC in the Danish Cancer Registry between 1980 and 2014 was evaluated based on the Charlson Comorbidity Index (CCI). Patients' risks of comorbid conditions compared to age- and gender-matched controls were estimated by odds ratios (OR). The impact of comorbidity on overall survival and cancer-specific mortality was evaluated by Cox regression and Kaplan-Meier survival analysis. Results: A total of 25,388 HNSCC patients were included (72.5% male; mean age 63.2 years at diagnosis; median follow-up 3.0 years). CCI at diagnosis was significantly higher in patients compared to controls (p < 0.001). The most common comorbid conditions among the patients were additional non-metastatic malignancy (10.9%) and cerebrovascular disease (7.7%). Compared to controls, patients had higher odds of metastatic malignancy (OR: 4.65; 95% CI: 4.21–5.15; p < 0.001), mild liver disease (OR: 6.95; 95% CI: 6.42–7.53; p < 0.001), and moderate-severe liver disease (OR: 7.28; 95% CI: 6.14–8.65; p < 0.001). The multivariate Cox analysis revealed increasing hazard ratios with increasing CCI and in coherence the Kaplan-Meier curves showed poorer overall survival and increased cancer-specific mortality in patients with higher CCI. Conclusion: HNSCC patients' comorbidity burden was significantly greater compared to the general population and increased comorbidity was correlated with increased cancer-related mortality. [ABSTRACT FROM AUTHOR]

Background: Isolated regional recurrences following head‐neck squamous‐cell carcinomas (HNSCC) are often accessible for curatively intended salvage treatment. Factors prognostic for outcome were investigated in a large cohort of HNSCC patients. Methods: In total, 1811 patients receiving curatively intended radiotherapy from 2007 to 2017 were reviewed and isolated cervical nodal recurrences were identified. Factors associated with survival and second recurrence were investigated using univariate and multivariate analyses. Results: Isolated regional recurrence was seen in 95/1811 (5.2%) patients. Eighty of 95 patients (84%) received salvage surgery. Two‐year survival after isolated regional recurrence was 40%. Overall survival (OS) and time to second recurrence were associated with resection status of the salvage surgery and presence of extranodal spread (ENS), while p16‐positive oropharyngeal squamous‐cell carcinoma (OPSCC) was associated with better OS. Conclusion: Long‐term survival after regional recurrence in HNSCC is possible. p16‐positive OPSCC, complete salvage surgery, and lack of ENS are associated with better outcome. [ABSTRACT FROM AUTHOR]

aim was to establish a large comprehensive database of patients with oral cavity squamous cell carcinoma (OSCC) to enable surveillance and research of the disease. Methods: All patients diagnosed and/or treated for OSCC at Rigshospitalet, University of Copenhagen, Denmark in the period 2000–2014 were included. Rigshospitalet is a tertiary treatment center and covers the Eastern Denmark region, comprising nearly half of the approximately 5.8 million inhabitants of Denmark. Data on numerous variables regarding general information of the patients at diagnosis, their primary cancer, recurrence, treatment, prior cancers, and secondary cancers were collected from the Danish Pathology Register and by evaluation of medical charts. Results: One thousand three hundred and ninety-nine OSCC patients were included in the database (62% males). The median age at diagnosis was 63 years (range: 23–99 years). The most common anatomical location was the floor of mouth (38%). Among patients with known stage, 70.0% were diagnosed in T-stage 1 or 2 and 64.9% were diagnosed in N-stage 0. Most patients were treated with primary surgery (81.7% among patients with known treatment), of these 44% received adjuvant radiotherapy after surgery. The overall age-standardized incidence of OSCC per 100,000 increased from 2.15 in 2000 to 3.04 in 2014, with a significant annual percent change of 3.2%. Conclusion: We have established a consecutive, population-based database of 1,399 OSCC patients. This creates a basis for multiple studies that will elaborate our understanding of OSCC, and hopefully improve diagnosis, treatment, and rehabilitation of OSCC patients. [ABSTRACT FROM AUTHOR]

• The mean tumor volume defined by PET, MRI and combined imaging and clinical information was larger the pathological-defined tumor volume. • Tumor volume defined from PET alone was smaller and had a smaller mismatch to the pathological defined tumor volume compared to MRI. • A five mm margin was sufficient to cover the pathology-defined tumor volume. In cancer treatment precise definition of the tumor volume is essential, but despite development in imaging modalities, this remains a challenge. Here, pathological tumor volumes from the surgical specimens were obtained and compared to tumor volumes defined from modern PET/MRI hybrid imaging. The purpose is to evaluate mismatch between the volumes defined from imaging and pathology was estimated and potential clinical impact. Twenty-five patients with head and neck squamous cell carcinoma were scanned on an integrated PET/MRI system prior to surgery. Three gross tumor volumes (GTVs) from the primary tumor site were delineated defined from MRI (GTV MRI), PET (GTV PET) and one by utilizing both anatomical images and clinical information (GTV ONCO). Twenty-five primary tumor specimens were extracted en bloc, scanned with PET/MRI and co-registered to the patient images. Each specimen was sectioned in blocks, sliced and stained with haematoxylin and eosin. All slices were digitalized and tumor delineated by a head and neck pathologist. The pathological tumor areas in all slices were interpolated yielding a pathological 3D tumor volume (GTV PATO). GTV PATO was compared with the imaging GTV's and potential mismatch was estimated. Thirteen patients were included. The mean volume of GTV ONCO was larger than the GTV's defined from PET or MRI. The mean mismatch of the GTV PATO compared to the GTV PET , GTV MRI and GTV ONCO was 31.9 %, 54.5 % and 27.9 % respectively, and the entire GTV PATO was only fully encompassed in GTV ONCO in 1 of 13 patients. However, after the addition of a clinical 5 mm margin the GTV PATO was fully encompassed in GTV ONCO in 11 out of 13 patients. Despite modern hybrid imaging modalities, a mismatch between imaging and pathological defined tumor volumes was observed in all patients. A 5 mm clinical margin was sufficient to ensure inclusion of the entire pathological volume in 11 out of 13 patients. [ABSTRACT FROM AUTHOR]

Objectives: Nasopharyngeal malignancies are reported having decreasing incidence and reduced mortality. This study provides a nationwide update of the incidence and survival in Denmark.Materials and Methods: The Danish Cancer Registry (DCR) and Central Population Register (CPR) were used to identify all patients registered with nasopharyngeal malignancies between 1980 and 2014 in Denmark. We evaluated the age-adjusted incidence rate (AAIR), average annual percent change (AAPC) and relative survival (RS) and also constructed age-population-cohort (APC) models.Results: 911 patients were identified with a male:female ratio of 2.2:1, a median age of 57.7 years (range 2.8-98.3 years) and an overall median follow-up time of 2.7 years (range 0-37 years). The AAIR was 0.39 cases per 100 000 in 1980 and 0.28 cases per 100 000 in 2014 with an AAPC of -3.2 (95% CI: -7.5; 1.2, p = 0.1). The overall 1-year and 5-year RS rates were 76.3% and 42.1%, respectively. We found a significant age effect in the APC model for the incidence of nasopharyngeal malignancies, but no significant cohort or period effects.Conclusion: The incidence of nasopharyngeal carcinomas has slightly decreased over the last four decades, however insignificantly. Meanwhile, the relative survival has increased significantly in Denmark since 1980. The cause of improved relative survival might be attributed to altered treatment practices. [ABSTRACT FROM AUTHOR]