Dual targeting of cancer metabolome and stress antigens affects transcriptomic heterogeneity and efficacy of engineered T cells.

Few cancers can be targeted efficiently by engineered T cell strategies. Here, we show that γδ T cell antigen receptor (γδ TCR)-mediated cancer metabolome targeting can be combined with targeting of cancer-associated stress antigens (such as NKG2D ligands or CD277) through the addition of chimeric co-receptors. This strategy overcomes suboptimal γ9δ2 TCR engagement of αß T cells engineered to express a defined γδ TCR (TEGs) and improves serial killing, proliferation and persistence of TEGs. In vivo, the NKG2D-CD28WT chimera enabled control only of liquid tumors, whereas the NKG2D-4-1BBCD28TM chimera prolonged persistence of TEGs and improved control of liquid and solid tumors. The CD277-targeting chimera (103-4-1BB) was the most optimal co-stimulation format, eradicating both liquid and solid tumors. Single-cell transcriptomic analysis revealed that NKG2D-4-1BBCD28TM and 103-4-1BB chimeras reprogram TEGs through NF-κB. Owing to competition with naturally expressed NKG2D in CD8+ TEGs, the NKG2D-4-1BBCD28TM chimera mainly skewed CD4+ TEGs toward adhesion, proliferation, cytotoxicity and less exhausted signatures, whereas the 103-4-1BB chimera additionally shaped the CD8+ subset toward a proliferative state.

Prophylactic pectoralis major flap to compensate for increased risk of pharyngocutaneous fistula in laryngectomy patients with low skeletal muscle mass (PECTORALIS): study protocol for a randomized controlled trial.

BACKGROUND: Total laryngectomy (TL) is a surgical procedure commonly performed on patients with advanced laryngeal or hypopharyngeal carcinoma. One of the most common postoperative complications following TL is the development of a pharyngocutaneous fistula (PCF), characterized by a communication between the neopharynx and the skin. PCF can lead to extended hospital stays, delayed oral feeding, and compromised quality of life. The use of a myofascial pectoralis major flap (PMMF) as an onlay technique during pharyngeal closure has shown potential in reducing PCF rates in high risk patients for development of PCF such as patients undergoing TL after chemoradiation and low skeletal muscle mass (SMM). Its impact on various functional outcomes, such as shoulder and neck function, swallowing function, and voice quality, remains less explored. This study aims to investigate the effectiveness of PMMF in reducing PCF rates in patients with low SMM and its potential consequences on patient well-being. METHODS: This multicenter study adopts a randomized clinical trial (RCT) design and is funded by the Dutch Cancer Society. Eligible patients for TL, aged ≥ 18 years, mentally competent, and proficient in Dutch, will be enrolled. One hundred and twenty eight patients with low SMM will be centrally randomized to receive TL with or without PMMF, while those without low SMM will undergo standard TL. Primary outcome measurement involves assessing PCF rates within 30 days post-TL. Secondary objectives include evaluating quality of life, shoulder and neck function, swallowing function, and voice quality using standardized questionnaires and functional tests. Data will be collected through electronic patient records. DISCUSSION: This study's significance lies in its exploration of the potential benefits of using PMMF as an onlay technique during pharyngeal closure to reduce PCF rates in TL patients with low SMM. By assessing various functional outcomes, the study aims to provide a comprehensive understanding of the impact of PMMF deployment. The anticipated results will contribute valuable insights into optimizing surgical techniques to enhance patient outcomes and inform future treatment strategies for TL patients. TRIAL REGISTRATION: NL8605, registered on 11-05-2020; International Clinical Trials Registry Platform (ICTRP).

Mental healthcare utilization among head and neck cancer patients: A longitudinal cohort study.

OBJECTIVE: To investigate utilization of mental healthcare among head and neck cancer (HNC) patients from diagnosis to 2 years after treatment, in relation to psychological symptoms, mental disorders, need for mental healthcare, and sociodemographic, clinical and personal factors. METHODS: Netherlands Quality of life and Biomedical Cohort study data as measured before treatment, at 3 and 6 months, and at 1 and 2 years after treatment was used (n = 610). Data on mental healthcare utilization (iMCQ), psychological symptoms (Hospital Anxiety and Depression Scale, Cancer Worry Scale), mental disorders (CIDI interview), need for mental healthcare (Supportive Care Needs Survey Short-Form 34, either as continuous outcome indicating the level of need or dichotomized into unmet need (yes/no)) and several sociodemographic, clinical and personal factors were collected. Factors associated with mental healthcare utilization were investigated using generalized estimating equations (p < 0.05). RESULTS: Of all HNC patients, 5%-9% used mental healthcare per timepoint. This was 4%-14% in patients with mild-severe psychological symptoms, 4%-17% in patients with severe psychological symptoms, 15%-35% in patients with a mental disorder and 5%-16% in patients with an unmet need for mental healthcare. Among all patients, higher symptoms of anxiety, a higher need for mental healthcare, lower age, higher disease stage, lower self-efficacy and higher social support seeking were significantly associated with mental healthcare utilization. CONCLUSION: Mental health care utilization among HNC patients is limited, and is related to psychological symptoms, need for mental healthcare, and sociodemographic, clinical and personal factors.

How do patients with head and neck cancer and low skeletal muscle mass experience cisplatin-based chemoradiotherapy? A qualitative study.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) face several physical, emotional, and psychological challenges throughout treatment. Cisplatin-based chemoradiotherapy (CRT) is an effective but toxic treatment, with an increased risk for toxicities in patients with low skeletal muscle mass (SMM). Consequently, these patients are anticipated to experience greater treatment-related difficulties. We aimed to explore the experiences of patients with HNSCC and low SMM regarding cisplatin-based CRT. METHODS: A descriptive qualitative study was conducted, interviewing seven patients 3 months after CRT using a topic guide. Thematic analysis of semi-structured interviews was conducted, to create a multi-dimensional understanding of patients' experiences during and after cisplatin-based CRT. RESULTS: Prior to CRT themes included pre-treatment information, expectations towards treatment and trial, psychosocial circumstances, and supporting network. During CRT themes included toxicities, psychosocial impact, and supporting network. After CRT themes included reflection on period during CRT, psychosocial circumstances, informal support from networks and healthcare workers, and ongoing toxicities. CONCLUSION: Most patients experience cisplatin-based CRT as a life-changing and distressing life event but cope through various strategies and supporting networks. Tailored counseling, ideally with on-demand consultations, is recommended. No differences were noted in patients' perceptions of their cisplatin regimen.

Surgery versus sclerotherapy versus combined therapy in head and neck lymphatic malformations in the pediatric population: systematic review and meta-analysis.

PURPOSE: To systematically review current literature on the treatment of lymphatic malformations (LMs) of the head and neck to guide treatment strategy. METHODS AND MATERIALS: A systematic review and meta-analysis of literature until 16 November 2021 was performed on treatments of LMs in the head and neck. RESULTS: Out of 9044 articles, 54 studies were eligible for inclusion with 26 studies providing detailed participant data. A total number of 1573 patients with a mean age of 21.22 months were analysed. Comparative meta-analysis did not reveal significant differences two proportions of volume reduction (≥ 50% and 100%) between sclerotherapy and surgical treatment. Regression demonstrated that positive predictors for volume reduction were surgery 17 (95% CI 0.26-34; p = 0.047) and treatment of macrocystic lesions 19 (95% CI 5.5-32; p = 0.006). Treatment of mixed lesions also demonstrated a trend towards achieving a greater volume reduction (p = 0.052). A higher de Serres stage of the lesion had a negative effect on the amount of volume reduction - 3.7 (95% CI - 7.0 to - 0.35; p = 0.030). CONCLUSION: This comprehensive meta-analysis demonstrated no significant difference in volume reduction between various treatment modalities at study level. However, individual patient data indicated that surgery and larger cyst types are associated with a significant higher percentage of volume reduction, whereas a higher de Serres stage negatively impacted the amount of volume reduction. These findings can be used for patient counseling and treatment planning based on cyst type and de Serres stage. However volume reduction constitutes just one objective within a more complex treatment spectrum.

Sinonasal mucosal melanoma in The Netherlands between 2001 and 2021: a clinical and epidemiological overview of 320 cases.

PURPOSE: Sinonasal mucosal melanoma (SNMM) is a rare malignancy, characterised by high (local) recurrence rates and poor survival. Comprehensive understanding of tumour etiology is currently lacking, which complicates adequate tumour treatment. Besides examining trends in incidence, this study aims to assess the association between clinical characteristics, treatment practices and patient outcomes, with the objective of establishing a baseline from which SNMM management can be enhanced. METHODS: All newly diagnosed SNMM cases in The Netherlands between 2001 and 2021 were included using data from The Netherlands Cancer Registry (NCR). RESULTS: A total of 320 patients were included. The annual incidence rate for the overall population was stable over the inclusion period with an annual percentage change (APC) of only - 0.01%. The 5-year overall survival (OS) and relative survival (RS) were 24.5 and 32.4%, respectively. Relative survival did not increase over time. The addition of adjuvant radiotherapy to surgery was not associated with a higher OS and RS compared to surgery alone. CONCLUSION: Sinonasal mucosal melanoma is a rare disease with stable incidence rates in the Netherlands between 2001 and 2021. There has been no improvement in survival over the course of the inclusion period. The study reaffirms that adjuvant radiotherapy does not seem to improve patient outcomes. Given the generally poor outcomes for SNMM patients, novel therapeutic options ought to be considered in order to improve care.

Oncological outcome of vocal cord-only radiotherapy for cT1-T2 glottic laryngeal squamous cell carcinoma.

PURPOSE: Early-stage glottic cancer can be treated with radiotherapy only. Modern radiotherapy solutions allow for individualized dose distributions, hypofractionation and sparing of organs at risk. The target volume used to be the entire voice box. This series describe the oncological outcome and toxicity of individualized vocal cord-only hypofractionated radiotherapy for early stage (cT1a-T2 N0). METHODS: Retrospective cohort study with patients treated in a single center between 2014 and 2020. RESULTS: A total of 93 patients were included. Local control rate was 100% for cT1a, 97% for cT1b and 77% for cT2. Risk factor for local recurrence was smoking during radiotherapy. Laryngectomy-free survival was 90% at 5 years. Grade III or higher late toxicity was 3.7%. CONCLUSION: Vocal cord-only hypofractionated radiotherapy appears to be oncologically safe in early-stage glottic cancer. Modern, image-guided radiotherapy led to comparable results as historical series with very limited late toxicity.

The potential of the Crystal Cam handheld gamma-camera for preoperative and intraoperative sentinel lymph node localization in early-stage oral cancer.

PURPOSE: Evaluating the Crystal Cam handheld gamma-camera for preoperative and intraoperative sentinel lymph node (SLN) localization in early-stage oral cancer. METHODS: The handheld gamma-camera was used complementary to conventional gamma-probe guidance for intraoperative SLN localization in 53 early-stage oral cancer patients undergoing SLN biopsy. In 36 of these patients, a blinded comparison was made between preoperative handheld gamma-camera and lymphoscintigraphy outcomes. Of those, the reliability for marking the SLN's location using both handheld gamma-camera and a 57Co-penpoint marker was evaluated in 15 patients. RESULTS: In the entire cohort, the handheld gamma-camera preoperatively detected 116/122 (95%) of SLNs identified by lymphoscintigraphy. In those patients where the observer was blinded for lymphoscintigraphy (n = 36), 71/77 (92%) SLNs were correctly identified by handheld gamma-camera. Overlooked SLNs by handheld gamma-camera were mainly located near the injection site. The SLN's marked location by handheld gamma-camera and 57Co-penpoint marker was considered accurate in 42/43 (98%) SLNs. The intraoperative use of the handheld gamma-camera led to the extirpation of 16 additional 'hot' lymph nodes in 14 patients, 4 of which harbored metastases, and prevented 2 patients (4%) from being erroneously staged negative for nodal metastasis. In those with follow-up ≥ 24 months or false-negative outcomes < 24 months following SLNB, a sensitivity of 82% and negative predictive value of 93% was obtained. CONCLUSION: The Crystal Cam handheld gamma-camera offers reliable preoperative and intraoperative SLN localization and might reduce the risk of missing a malignant SLN during surgery. Detecting SLNs near the injection site by handheld gamma-camera remains challenging.

Complications related to the Cook-Swartz implantable Doppler probe use in head and neck microvascular reconstruction: a systematic review.

PURPOSE: Vascular perfusion research has been dedicated to identify inexpensive, effective, and easy to use methods to assess free flap perfusion for both buried and non-buried flaps. METHODS: Systematic review of complications in patients underwent Head and Neck microsurgical reconstruction and vascular implantable Doppler monitoring. RESULTS: Sixteen articles were included for qualitative analysis. 2535 (92.2%) patients received IDP monitorization. Venous thrombosis was the most common vascular complication effecting 28 (1.1%). Regarding complications potentially related to the use of the IDP, just one study described the presence of granuloma formation along the suture line in 2 (0.07%) patients. CONCLUSIONS: Our findings indicated that Cook-Swartz IDP will represents a safe and effective device for FF monitoring in HN reconstructive micro-surgery. A detailed prospective registration of the results and complications related to the use of IDP remains mandatory to precisely estimate results, cost, and complications.

Esophageal Second Primary Tumors in Patients With Head and Neck Squamous Cell Carcinoma: Incidence, Risk Factors, and Overall Survival.

INTRODUCTION: The aim of this registry-based cohort study was to evaluate the potential role of endoscopic esophageal surveillance for esophageal second primary tumors (ESPTs) in Western patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Outcomes were cumulative incidence and risk factors for ESPTs and its effect on overall survival. RESULTS: A total of 47 ESPTs were observed in 1,708 patients with HNSCC, with 10-year cumulative incidence (95% confidence interval) of 2.9% (2.1-3.7). Alcohol and HNSCC location were significant predictors for ESPTs. ESPTs significantly increased the risk of dying (adjusted hazard ratio 3.36, 95% confidence interval 2.16-5.22). DISCUSSION: Endoscopic esophageal surveillance of Western patients with HNSCC with high risk of ESPTs seems justified.

Image-guided surgery in oral cancer: toward improved margin control.

PURPOSE OF REVIEW: The aim of this review is to discuss recent studies on the assessment of tumor extension and resection margins by different intraoperative techniques allowing for image-guided surgery of oral cancer. RECENT FINDINGS: There are different in-vivo and ex-vivo intraoperative techniques to improve margin control of which intraoperative ultrasound and targeted fluorescence-guided resections have high potential clinical value and are closest to clinical implementation. SUMMARY: In oral cancer surgery, resection margins, particularly deep margins, are often inadequate. Intraoperative frozen section does not improve resection margin control sufficiently. Specimen-driven intraoperative assessment for gross analysis of suspected margins reduces the amount of positive resection margins substantially but leaves still room for improvement. Mucosal staining methods, optical coherence tomography and narrow band imaging can only be used for superficial (mucosal) resection margin control. Spectroscopy is under investigation, but clinical data are scarce. Intraoperative ex-vivo imaging of the resection specimen by magnetic resonance and PET/computed tomography may be used to assess resection margins but needs more research. Intraoperative in-vivo ad ex-vivo ultrasound and targeted fluorescence imaging have high potential clinical value to guide oral cancer resections and are closest to clinical implementation for improved margin control.

Within-patient comparison between [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy and [99mTc]Tc-tilmanocept lymphoscintigraphy for sentinel lymph node detection in oral cancer: a pilot study.

PURPOSE: To compare sentinel lymph node (SLN) identification using [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy to [99mTc]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 [99mTc]Tc-tilmanocept without the interference of [68Ga]Ga-tilmanocept in these patients. METHODS: This prospective within-patient comparison pilot study evaluated SLN identification by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy compared to conventional lymphoscintigraphy using [99mTc]Tc-tilmanocept (~ 74 MBq) in 10 early-stage oral cancer patients scheduled for SLN biopsy. After conventional [99mTc]Tc-tilmanocept lymphoscintigraphy, patients underwent peritumoral administration of [68Ga]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 [99mTc]Tc-tilmanocept lymphoscintigraphy, all except one were also identified by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy. [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy identified 4 additional SLNs near the injection site, of which two harbored metastases. Lymphatic vessels transporting [68Ga]Ga-tilmanocept were identified by PET/CT lymphoscintigraphy in 80% of patients, while draining lymphatic vessels were visualized by [99mTc]Tc-tilmanocept lymphoscintigraphy in 20% of patients. Of the 33 SLNs identified by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy, 30 (91%) were intraoperatively localized under conventional gamma-probe guidance. CONCLUSION: [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy provided more accurate identification of SLNs and improved visualization of lymphatic vessels compared to [99mTc]Tc-tilmanocept lymphoscintigraphy. When combined with peritumoral administration of [99mTc]Tc-tilmanocept, SLNs detected by [68Ga]Ga-tilmanocept PET/CT lymphoscintigraphy can be reliably localized during surgery under conventional gamma-probe guidance.

Association of histological features with laryngeal squamous cell carcinoma recurrences: a population-based study of 1502 patients in the Netherlands.

BACKGROUND: Recurrences remain an important problem in laryngeal squamous cell carcinoma. Little has been described about histological characteristics of the primary laryngeal tumor that may be associated with recurrences. Identifying risk factors for recurrences might help in adapting treatment or follow-up. Using real-life population-based data, we aimed to identify histological features of the primary tumor associated with recurrences and overall survival. MATERIAL AND METHODS: Demographic, clinical and treatment information on all first primary invasive laryngeal tumors diagnosed in 2010-2014 (N = 3705) were extracted from the population-based nationwide Netherlands cancer registry (NCR) and linked to PALGA, the nationwide Dutch pathology registry, to obtain data on histological factors and recurrences. For a random 1502 patients histological information i.e., keratinization, perineural invasion (PNI+), vascular invasion (VI+), growth pattern, degree of differentiation, extracapsular spread (ECS+), cartilage- and bone invasion and extralaryngeal extension, was manually extracted from narrative pathology reports and analyzed for locoregional recurrence and overall survival using cox regression analysis. RESULTS: In total, 299 patients developed a locoregional recurrence and 555 patients died. Keratinization (HR = 0.96 (95%CI: 0.68-1.34) p = 0.79), two or three adverse characteristics (PNI+, VI+, non-cohesive growth) (HR = 1.38 (95% CI: 0.63-3.01) p = 0.42), and ECS+ (HR = 1.38 (95% CI: 0.48-4.02) p = 0.55) were not associated to recurrence. For death, also no significant association was found. CONCLUSION: In this population-based real-life dataset on laryngeal carcinoma in the Netherlands, histological factors were not associated with locoregional recurrences or overall survival, but future studies should investigate the role of these features in treatment decisions.

Nutritional interventions in patients with head and neck cancer undergoing chemoradiotherapy: Current practice at the Dutch Head and Neck Oncology centres.

OBJECTIVE: To assess variations in nutritional interventions during chemoradiotherapy (CRT) among the Dutch Head and Neck Oncology centres (HNOCs). METHODS: An online questionnaire about nutritional interventions and dietetic practices was sent to 14 oncology dietitians of the HNOCs. RESULTS: The response rate was 93%. The number of scheduled dietetic consultations varied from two to seven during CRT. Most centres (77%) reported using a gastrostomy for tube feeding in the majority of patients. Gastrostomies were placed prophylactically upon indication (39%) or in all patients (15%), reactive (15%), or both (31%). For calculating energy requirements, 54% of the dietitians used the Food and Agriculture Organization/World Health Organization and United Nations University (FAO/WHO/UNU) formula and 77% uses 1.2-1.5 g/kg body weight for calculating protein requirements. Almost half of the centres (46%) reported to remove the gastrostomy between 8 and 12 weeks after CR. Most centres (92%) reported to end dietary treatment within 6 months after CRT. CONCLUSION: This study shows substantial variation in dietetic practice, especially in the use of a gastrostomy for tube feeding, between the HNOCs. There is a need for concise dietetic guidelines.

Feasibility of a supervised and home-based tailored exercise intervention in head and neck cancer patients during chemoradiotherapy.

OBJECTIVE: Chemoradiotherapy (CRT) for head and neck cancer (HNC) is associated with high toxicity that adversely affects physical functioning, body composition, fatigue, quality of life and treatment outcomes. Exercise interventions during treatment might counteract these negative effects. We therefore assessed the feasibility of an exercise programme for HNC patients during CRT. METHODS: Forty patients were offered a tailored 10-week endurance and resistance training with supervised and home-based sessions. Feasibility endpoints were (1) adherence (main outcome): ≥60% attendance; (2) recruitment: ≥30%; (3) retention rate: ≥85% and (4) compliance rate: ≥60%. Physical performance, muscle strength, body composition, quality of life and fatigue were assessed pre- and post-intervention. RESULTS: Overall adherence was 54%. The recruitment rate was 36%, and the retention rate was 65%. Compliance to the supervised intervention protocol was 66%. Statistically significant decreases were found in mean grip strength, fat-free mass and clinically relevant deteriorations on several domains of quality of life, and fatigue subscales were found. CONCLUSION: We conclude that this exercise programme for HNC patients during CRT in its current form is feasible for only a minority of patients. We suggest adaptations to improve adherence and retention rates for a definitive multicentre trial. TRIAL REGISTRATION: This study is registered at the Netherlands Trial Register (NTR7305), 6 June 2018, retrospectively registered.

Image-based analysis of skeletal muscle mass predicts cisplatin dose-limiting toxicity in patients with locally advanced head and neck cancer.

PURPOSE: Evidence suggests that patients' skeletal muscle mass (SMM) can predict the patients at risk for cisplatin dose-limiting toxicities (DLT). Cisplatin is currently dosed on body surface area (BSA). The predictive value of SMM for cisplatin DLT in patients with locally advanced head and neck cancer (LA-HNC) is investigated. METHODS: Patients with LA-HNC treated with cisplatin-based chemoradiotherapy (CRT) were included. SMM was measured using pre-treatment scans. Logistic regression analysis was performed to identify the predictive impact of low SMM for DLT. RESULTS: In total, 343 patients were included of which 199 patients (58.0%) had low SMM and 154 patients (44.9%) experienced cisplatin DLT. In multivariate analysis, low SMM at diagnosis was the only predictive factor for DLT (HR 1.8, 95% CI 1.1-2.9). CONCLUSIONS: Low SMM was associated with an increased risk of DLT. Trials are needed to investigate cisplatin dosing with consideration of SMM rather than solely BSA.

Dysphagia, trismus and speech impairment following radiation-based treatment for advanced stage oropharyngeal carcinoma: a one-year prospective evaluation.

OBJECTIVE: The objective was to assess swallowing, mouth opening and speech function during the first year after radiation-based treatment (RT(+)) after introduction of a dedicated preventive rehabilitation program for stage III-IV oropharyngeal carcinoma (OPC). METHODS: Swallowing, mouth opening and speech function were collected before and at six- and twelve-month follow-up after RT(+) for OPC as part of ongoing prospective assessments by speech-language pathologists . RESULTS: Objective and patient-perceived function deteriorated until 6 months and improved until 12 months after treatment, but did not return to baseline levels with 25%, 20% and 58% of the patients with objective dysphagia, trismus and speech problems, respectively. Feeding tube dependency and pneumonia prevalence was low. CONCLUSION: Despite successful implementation, a substantial proportion of patients still experience functional limitations after RT(+) for OPC, suggesting room for improvement of the current rehabilitation program. Pretreatment sarcopenia seems associated with worse functional outcomes and might be a relevant new target for rehabilitation strategies.

Sentinel lymph node detection in oral cancer: a within-patient comparison between [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid.

PURPOSE: Sentinel 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. METHODS: A 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. RESULTS: The 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.

Multiparametric functional MRI and 18F-FDG-PET for survival prediction in patients with head and neck squamous cell carcinoma treated with (chemo)radiation.

OBJECTIVES: To assess (I) correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and 18F-FDG-PET/CT imaging parameters capturing tumor characteristics and (II) their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. METHODS: Between 2014 and 2018, patients with histopathologically proven HNSCC, planned for curative (chemo) radiotherapy, were prospectively included. Pretreatment clinical, anatomical, and functional imaging parameters (obtained by DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT) were extracted for primary tumors (PT) and lymph node metastases. Correlations and differences between parameters were assessed. The predictive value of LRFS and OS was assessed, performing univariable, multivariable Cox and CoxBoost regression analyses. RESULTS: In total, 70 patients were included. Significant correlations between 18F-FDG-PET parameters and DWI-/DCE volume parameters were found (r > 0.442, p < 0.002). The combination of HPV (HR = 0.903), intoxications (HR = 1.065), PT ADCGTV (HR = 1.252), Ktrans (HR = 1.223), and Ve (HR = 1.215) was predictive for LRFS (C-index = 0.546; p = 0.023). N-stage (HR = 1.058), HPV positivity (HR = 0.886), hypopharyngeal tumor location (HR = 1.111), ADCGTV (HR = 1.102), ADCmean (HR = 1.137), D* (HR = 0.862), Ktrans (HR = 1.106), Ve (HR = 1.195), SUVmax (HR = 1.094), and TLG (HR = 1.433) were predictive for OS (C-index = 0.664; p = 0.046). CONCLUSIONS: Functional imaging parameters, performing DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT, yielded complementary value in capturing tumor characteristics. More specific, intoxications, HPV-negative status, large tumor volume-related parameters, high permeability (Ktrans), and high extravascular extracellular space (Ve) parameters were predictive for adverse locoregional recurrence-free survival and adverse overall survival. Low cellularity (high ADC) and high metabolism (high SUV) were additionally predictive for decreased overall survival. These different predictive factors added to estimated locoregional and overall survival. KEY POINTS: • Parameters of DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT were able to capture complementary tumor characteristics. • Multivariable analysis revealed that intoxications, HPV negativity, large tumor volume and high vascular permeability (Ktrans), and extravascular extracellular space (Ve) were complementary predictive for locoregional recurrence. • In addition to predictive parameters for locoregional recurrence, also high cellularity (low ADC) and high metabolism (high SUV) were complementary predictive for overall survival.

Depression and related factors after oral oncological treatment: a 5-year prospective cohort study.

PURPOSES: Being diagnosed with oral cancer is a life-threatening life event. It often induces social, emotional and psychological consequences and may cause depressive disorders. The primary aim of this study was to identify and quantify the personal and clinical characteristics involved in depression for patients who have been treated for oral cavity malignancies, with a 5-year follow-up period after treatment. The secondary aim of this study was to identify the clinical factors that increase a patient's risk of experiencing depression 5 years after treatment. METHODS: Patients with primary oral cancer were assessed for up to 5 years after primary treatment. A mixed-model analysis was performed, with depression measured by the Center for Epidemiologic Studies Depression Scale as outcome measure. RESULTS: A total of 141 patients were included in the study. Factors associated with depression were gender, tumour location and having an emotion-oriented coping style. The occurrence of depression within 5 years after treatment could be reliably predicted by a patient's gender, the location of their tumour and the extent to which they had an emotion-oriented coping style. CONCLUSIONS: This study revealed that being female, having a maxillary tumour and having an emotion-oriented coping style are associated with higher levels of depressive symptoms in patients treated for oral cancer up to 5 years post-treatment. A substantial proportion of the patients with oral cancer experienced high levels of depression both before and after their treatment, suggesting that adequate diagnostics and care are needed to try to prevent severe depression in these patients.