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Purpose To assess the role of single-photon emission computed tomography with computed tomography (SPECT-CT) for the identification of sentinel lymph nodes (SLNs) in patients with early stage (T1–T2) oral cancer and a clinically negative neck (cN0). Methods In addition to planar lymphoscintigraphy, SPECT-CT was performed in 66 consecutive patients with early stage oral cancer and a clinically negative neck. The addition of SPECT-CT to planar images was retrospectively analyzed for the number of additional SLNs, more precise localization of SLNs, and importance of anatomical information by a team consisting of a nuclear physician, surgeon, and investigator. Results Identification rate for both imaging modalities combined was 98% (65/66). SPECT-CT identified 15 additional SLNs in 14 patients (22%). In 2/15 (13%) of these additional SLNs, the only metastasis was found, resulting in an upstaging rate of 3% (2/65). In 20% of the patients with at least one positive SLN, the only positive SLN was detected due to the addition of SPECT-CT. SPECT-CT was considered to add important anatomical information in two patients (3%). In 5/65 (8%) of the patients initially scored SLNs on planar lymphoscintigrams were scored as non-SLNs when SPECT-CT was added. There were four false-negative SLN biopsy procedures in this cohort. Conclusions The addition of SPECT-CT to planar lymphoscintigraphy is recommended for the identification of more (positive) SLNs and better topographical orientation for surgery in sentinel lymph node biopsy for early stage oral cancer.

Purpose To compare sentinel lymph node (SLN) identification using [ 68 Ga]Ga-tilmanocept PET/CT lymphoscintigraphy to [ 99m Tc]Tc-tilmanocept lymphoscintigraphy (including SPECT/CT) in early-stage oral cancer. Furthermore, to assess whether reliable intraoperative SLN localization can be performed with a conventional portable gamma-probe using [ 99m Tc]Tc-tilmanocept without the interference of [ 68 Ga]Ga-tilmanocept in these patients. Methods This prospective within-patient comparison pilot study evaluated SLN identification by [ 68 Ga]Ga-tilmanocept PET/CT lymphoscintigraphy compared to conventional lymphoscintigraphy using [ 99m Tc]Tc-tilmanocept (~ 74 MBq) in 10 early-stage oral cancer patients scheduled for SLN biopsy. After conventional [ 99m Tc]Tc-tilmanocept lymphoscintigraphy, patients underwent peritumoral administration of [ 68 Ga]Ga-tilmanocept (~ 10 MBq) followed by PET/CT acquisition initiated 15 min after injection. Intraoperative SLN localization was performed under conventional portable gamma-probe guidance the next day; the location of harvested SLNs was correlated to both lymphoscintigraphic images in each patient. Results A total of 24 SLNs were identified by [ 99m Tc]Tc-tilmanocept lymphoscintigraphy, all except one were also identified by [ 68 Ga]Ga-tilmanocept PET/CT lymphoscintigraphy. [ 68 Ga]Ga-tilmanocept PET/CT lymphoscintigraphy identified 4 additional SLNs near the injection site, of which two harbored metastases. Lymphatic vessels transporting [ 68 Ga]Ga-tilmanocept were identified by PET/CT lymphoscintigraphy in 80% of patients, while draining lymphatic vessels were visualized by [ 99m Tc]Tc-tilmanocept lymphoscintigraphy in 20% of patients. Of the 33 SLNs identified by [ 68 Ga]Ga-tilmanocept PET/CT lymphoscintigraphy, 30 (91%) were intraoperatively localized under conventional gamma-probe guidance. Conclusion [ 68 Ga]Ga-tilmanocept PET/CT lymphoscintigraphy provided more accurate identification of SLNs and improved visualization of lymphatic vessels compared to [ 99m Tc]Tc-tilmanocept lymphoscintigraphy. When combined with peritumoral administration of [ 99m Tc]Tc-tilmanocept, SLNs detected by [ 68 Ga]Ga-tilmanocept PET/CT lymphoscintigraphy can be reliably localized during surgery under conventional gamma-probe guidance.

BackgroundAdvanced salivary gland cancers become difficult to treat when they are technically irresectable and radiotherapy limits are exceeded. There is also an unmet need to improve palliative systemic therapy. Salivary glands depict the Prostate-Specific Membrane Antigen (PSMA) on 68Ga-PSMA-PET/CT, a transmembrane protein that is targeted for diagnosis and treatment of advanced prostate cancer. Some salivary gland carcinomas also express PSMA.MethodsThis study aimed to retrospectively evaluate the effectiveness of 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancers, as a last resort treatment. Patients with serious tumour-related discomfort for whom no regular option was available were selected and critically re-assessed by the tumour board. Radionuclide therapy eligibility was confirmed when tumour targeting was greater than liver SUVmax on 68Ga-PSMA-PET/CT. The protocol aimed at four cycles of 6.0–7.4 GBq 177Lu-PSMA-617 every 6–8 weeks. Clinical response was evaluated by questionnaires and radiological response by 68Ga-PSMA-PET/CT.ResultsSix patients were treated with 177Lu-PSMA: four adenoid cystic carcinomas, one adenocarcinoma NOS and one acinic cell carcinoma. In two patients, radiological response was observed, showing either stable disease or a partial response, and four patients reported immediate relief of tumour-related symptoms. Most reported side effects were grade 1–2 fatigue, nausea, bone pain and xerostomia. Four patients prematurely discontinued therapy: three due to disease progression and one due to demotivating (grade 1) side-effects.ConclusionsPalliative 177Lu-PSMA therapy for salivary gland cancer may lead to rapid relief of tumour-associated discomfort and may even induce disease stabilization. It is safe, relatively well tolerated and can be considered when regular treatment options fail.

Background/Objectives: Total glossectomy (TG) is among the most radical operations in head and neck oncology. While it can achieve local control in advanced oral tongue squamous cell carcinoma, survival and functional outcomes are inconsistently reported, and pooled estimates remain limited. This study aimed to systematically evaluate survival, functional recovery, and prognostic factors following primary TG. Methods: We conducted a proportional meta-analysis of studies reporting outcomes after primary TG for oral tongue squamous cell carcinoma. Studies combining TG with laryngectomy, salvage settings, or second primary tumors were excluded. Two reviewers independently screened, extracted data, and assessed quality with the Newcastle–Ottawa Scale. Pooled 1-, 3-, and 5-year overall survival (OS) with 95% confidence intervals (CIs) was calculated using a random-effects model. Heterogeneity was quantified (Q, τ2, I2), and robustness was assessed with sensitivity analyses. Disease-free survival (DFS) and functional outcomes (swallowing, airway, speech) were narratively summarized due to inconsistent reporting. Results: Ten studies (1992–2022) comprising 261 patients met the criteria. Pooled OS was 81% (95% CI, 71–90) at 1 year, 55% (95% CI, 41–68) at 3 years, and 47% (95% CI, 27–67) at 5 years, with rising heterogeneity (I2 up to 89%). The post-2000 series showed improved 5-year OS (63%). Adverse prognostic factors included advanced T stage, nodal disease (N+), and positive margins. Functional recovery varied: 15–30% remained gastrostomy-dependent and 20–25% aspirated, while reconstruction and structured rehabilitation improved outcomes. Conclusions: Survival after TG declines beyond the first year, with under half surviving at 5 years, though modern outcomes appear better. Significant functional morbidity underscores the need for multidisciplinary care. Future biomarker-driven studies should refine patient selection and prognostic assessment.

BackgroundRadiomics is aimed at image-based tumor phenotyping, enabling application within clinical-decision-support-systems to improve diagnostic accuracy and allow for personalized treatment. The purpose was to identify predictive 18-fluor-fluoro-2-deoxyglucose (18F-FDG) positron-emission tomography (PET) radiomic features to predict recurrence, distant metastasis, and overall survival in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy.MethodsBetween 2012 and 2018, 103 retrospectively (training cohort) and 71 consecutively included patients (validation cohort) underwent 18F-FDG-PET/CT imaging. The 434 extracted radiomic features were subjected, after redundancy filtering, to a projection resulting in outcome-independent meta-features (factors). Correlations between clinical, first-order 18F-FDG-PET parameters (e.g., SUVmean), and factors were assessed. Factors were combined with 18F-FDG-PET and clinical parameters in a multivariable survival regression and validated. A clinically applicable risk-stratification was constructed for patients’ outcome.ResultsBased on 124 retained radiomic features from 103 patients, 8 factors were constructed. Recurrence prediction was significantly most accurate by combining HPV-status, SUVmean, SUVpeak, factor 3 (histogram gradient and long-run-low-grey-level-emphasis), factor 4 (volume-difference, coarseness, and grey-level-non-uniformity), and factor 6 (histogram variation coefficient) (CI = 0.645). Distant metastasis prediction was most accurate assessing metabolic-active tumor volume (MATV)(CI = 0.627). Overall survival prediction was most accurate using HPV-status, SUVmean, SUVmax, factor 1 (least-axis-length, non-uniformity, high-dependence-of-high grey-levels), and factor 5 (aspherity, major-axis-length, inversed-compactness and, inversed-flatness) (CI = 0.764).ConclusionsCombining HPV-status, first-order 18F-FDG-PET parameters, and complementary radiomic factors was most accurate for time-to-event prediction. Predictive phenotype-specific tumor characteristics and interactions might be captured and retained using radiomic factors, which allows for personalized risk stratification and optimizing personalized cancer care.Trial registrationTrial NL3946 (NTR4111), local ethics commission reference: Prediction 2013.191 and 2016.498. Registered 7 August 2013, https://www.trialregister.nl/trial/3946

Background: The aim of the present systematic review (SR) is to compile evidence regarding the use of radiomic-based machine learning (ML) models for predicting human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) patients and to assess their reliability, methodological frameworks, and clinical applicability. The SR was conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD42025640065). Methods: Using the PICOS framework, the review question was defined as follows: “Can radiomic-based ML models accurately predict HPV status in OPSCC?” Electronic databases (Cochrane, Embase, IEEE Xplore, BVS, PubMed, Scopus, Web of Science) and gray literature (arXiv, Google Scholar and ProQuest) were searched. Retrospective cohort studies assessing radiomics for HPV prediction were included. Risk of bias (RoB) was evaluated using Prediction model Risk Of Bias ASsessment Tool (PROBAST), and data were synthesized based on imaging modality, architecture type/learning modalities, and the presence of external validation. Meta-analysis was performed for externally validated models using MetaBayesDTA and RStudio. Results: Twenty-four studies including 8627 patients were analyzed. Imaging modalities included computed tomography (CT), magnetic resonance imaging (MRI), contrast-enhanced computed tomography (CE-CT), and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Logistic regression, random forest, eXtreme Gradient Boosting (XGBoost), and convolutional neural networks (CNNs) were commonly used. Most datasets were imbalanced with a predominance of HPV+ cases. Only eight studies reported external validation results. AUROC values ranged between 0.59 and 0.87 in the internal validation and between 0.48 and 0.91 in the external validation results. RoB was high in most studies, mainly due to reliance on p16-only HPV testing, insufficient events, or inadequate handling of class imbalance. Deep Learning (DL) models achieved moderate performance with considerable heterogeneity (sensitivity: 0.61; specificity: 0.65). In contrast, traditional models provided higher, more consistent performance (sensitivity: 0.72; specificity: 0.77). Conclusions: Radiomic-based ML models show potential for HPV status prediction in OPSCC, but methodological heterogeneity and a high RoB limit current clinical applicability.

Oral squamous-cell carcinomas arise in mucosal linings of the oral cavity and frequently metastasise to regional lymph nodes in the neck. The presence of nodal metastases is a determinant of prognosis and clinical management. The neck is staged by palpation and imaging, but accuracy of these techniques to detect small metastases is low. In general, 30–40% of patients will have occult nodal disease and will develop clinically detectable lymph-node metastases when the neck is left untreated. The choice at present is either elective treatment or careful observation followed by treatment of the neck in patients who develop manifest metastases. These unsatisfying therapeutic options have been the subject of debate for decades. Recent developments in staging of the neck, including expression profiling and sentinel lymph-node biopsy, will allow more personalised management of the neck.

Background During posttreatment surveillance of head and neck cancer patients, imaging is insufficiently accurate for the early detection of relapsing disease. Free circulating tumor DNA (ctDNA) may serve as a novel biomarker for monitoring tumor burden during posttreatment surveillance of these patients. In this exploratory study, we investigated whether low level ctDNA in plasma of head and neck cancer patients can be detected using Droplet Digital PCR (ddPCR). Methods TP53 mutations were determined in surgically resected primary tumor samples from six patients with high stage (II-IV), moderate to poorly differentiated head and neck squamous cell carcinoma (HNSCC). Subsequently, mutation specific ddPCR assays were designed. Pretreatment plasma samples from these patients were examined on the presence of ctDNA by ddPCR using the mutation-specific assays. The ddPCR results were evaluated alongside clinicopathological data. Results In all cases, plasma samples were found positive for targeted TP53 mutations in varying degrees (absolute quantification of 2.2–422 mutational copies/ml plasma). Mutations were detected in wild-type TP53 background templates of 7667–156,667 copies/ml plasma, yielding fractional abundances of down to 0.01%. Conclusions Our results show that detection of tumor specific TP53 mutations in low level ctDNA from HNSCC patients using ddPCR is technically feasible and provide ground for future research on ctDNA quantification for the use of diagnostic biomarkers in the posttreatment surveillance of HNSCC patients.

PurposeSentinel lymph node (SLN) biopsy has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). [99mTc]Tc-tilmanocept may be of benefit in OSCC with complex lymphatic drainage patterns and close spatial relation to SLNs.MethodsA prospective within-patient evaluation study was designed to compare [99mTc]Tc-tilmanocept with [99mTc]Tc-nanocolloid for SLN detection. A total of 20 patients with early-stage OSCC were included, who underwent lymphoscintigraphy with both tracers. Both lymphoscintigraphic images of each patient were evaluated for SLN detection and radiotracer distribution at 2–4 h post-injection.ResultsThe injection site’s remaining radioactivity was significantly lower for [99mTc]Tc-tilmanocept (29.9%), compared with [99mTc]Tc-nanocolloid (60.9%; p < 0.001). Radioactive uptake in SLNs was significantly lower for [99mTc]Tc-tilmanocept (1.95%) compared with [99mTc]Tc-nanocolloid (3.16%; p = 0.010). No significant difference was seen in SLN to injection site ratio in radioactivity between [99mTc]Tc-tilmanocept (0.066) and [99mTc]Tc-nanocolloid (0.054; p = 0.232). A median of 3.0 and 2.5 SLNs were identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.297). Radioactive uptake in higher echelon nodes was not significantly different between [99mTc]Tc-tilmanocept (0.57%) and [99mTc]Tc-nanocolloid (0.86%) (p = 0.052). A median of 2.0 and 2.5 higher echelon nodes was identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.083).Conclusion[99mTc]Tc-tilmanocept had a higher injection site clearance, but at the same time a lower uptake in the SLN, resulting in an SLN to injection site ratio, which was not significantly different from [99mTc]Tc-nanocolloid. The relatively low-radioactive uptake in SLNs of [99mTc]Tc-tilmanocept may limit intraoperative detection of SLNs, but can be overcome by a higher injection dose.