The limited value of sentinel lymph node biopsy in lentigo maligna melanoma: A nomogram based on the results of 29 years of the nationwide dutch pathology registry (PALGA).

BACKGROUND: Lentigo maligna melanoma (LMM) predominantly presents in the head and neck of the elderly. The value of sentinel lymph node biopsy (SLNB) for LMM patients remains to be determined, as the reported average yield of positive lymph nodes is less than 10%. In this nationwide cohort study, we wanted to identify LMM patients with an increased risk of SLNB-positivity. METHODS: LMM with an SLNB indication according to the 8th AJCC melanoma guidelines were retrospectively identified from the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). A penalized (LASSO) logistic regression analysis was performed to determine the optimal combination of clinicopathological factors to predict a positive SLNB. RESULTS: Between 1991 and 2020, 1989 LMM patients met our inclusion criteria. SLNB was performed in 16.7% (n = 333) and was positive in 7.5% (25/333). The false-negative rate was 21.9%. Clinically detectable regional lymph node (LN) metastases were found in 1.3% (n = 25). Clinicopathological characteristics best predictive for SLNB-positivity (Odds ratio; 95% CI) were age (0.95; 0.91-0.99), ulceration 1.59 (0.44-4.83), T4-stage (1.81; 0.43-6.2), male sex (1.97; 0.79-5.27), (lymph)angioinvasion (5.07; 0.94-23.31), and microsatellites (7.23; 1.56-32.7) (C-statistic 0.75). During follow-up, regional LN recurrences were detected in 4.2% (83/1989) of patients, of which the majority (74/83) had no evidence of regional LN metastases at baseline. CONCLUSION: Our findings confirm the limited SLNB-positivity in LMM patients. Based on the identified high-risk clinicopathological features, a nomogram was developed to predict the risk of a positive SLNB.

A cohort analysis of surgically treated primary head and neck lentigo maligna (melanoma): Prognostic value of melanoma subtype and new insights in the clinical value of guideline adherence.

BACKGROUND: Knowledge about lentigo maligna (melanoma) (LM/LMM) and its associated prognostic clinicopathological characteristics are limited compared to that of non-LM/LMM subtypes. The current study aimed to determine the clinical relevance of the LM/LMM subtype and its influence on recurrence and survival outcomes. METHODS: All consecutive cases of primary cutaneous head and neck LM/LMM treated by wide local excision over a ten-year period were retrospectively reviewed and compared to non-LM/LMM. Clinical outcome and prognostic factors were assessed by cumulative incidence and competing risk analyses. RESULTS: A total of 345 patients were identified. Specific clinicopathological characteristics such as lower median Breslow thickness (1.6 mm versus 2.1 mm; P = 0.013), association with diagnostic sampling errors (17.3% versus 5.2%; P = 0.01), and increased risk of local recurrences due to incomplete resection (18.7% versus 2.3%; P < 0.001), were significantly associated with LM/LMM. Guideline adherence was similar between the two study groups. The positive nodal status at baseline for LMM was low compared to non-LM/LMM (4.2% vs 17.9%; P = 0.037). The LMM subtype, facial localization, and reduced surgical margins (i.e., guideline non-adherence) were not shown to be independent prognostic factors for disease-free, melanoma-specific, or overall survival after correction for competing risks such as patient age and Breslow thickness. CONCLUSIONS: The LMM subtype was not shown to be prognostically different from non-LM/LMM when corrected for other variables of influence such as patient age and Breslow thickness. Reduced resection margins did not seem to affect disease-free, and melanoma-specific survival and warrant LM/LMM-specific guidelines. Further research is needed to evaluate the value of SLNB in LMM patients.

Dynamic MRI of swallowing: real-time volumetric imaging at 12 frames per second at 3 T.

OBJECTIVE: Dysphagia or difficulty in swallowing is a potentially hazardous clinical problem that needs regular monitoring. Real-time 2D MRI of swallowing is a promising radiation-free alternative to the current clinical standard: videofluoroscopy. However, aspiration may be missed if it occurs outside this single imaged slice. We therefore aimed to image swallowing in 3D real time at 12 frames per second (fps). MATERIALS AND METHODS: At 3 T, three 3D real-time MRI acquisition approaches were compared to the 2D acquisition: an aligned stack-of-stars (SOS), and a rotated SOS with a golden-angle increment and with a tiny golden-angle increment. The optimal 3D acquisition was determined by computer simulations and phantom scans. Subsequently, five healthy volunteers were scanned and swallowing parameters were measured. RESULTS: Although the rotated SOS approaches resulted in better image quality in simulations, in practice, the aligned SOS performed best due to the limited number of slices. The four swallowing phases could be distinguished in 3D real-time MRI, even though the spatial blurring was stronger than in 2D. The swallowing parameters were similar between 2 and 3D. CONCLUSION: At a spatial resolution of 2-by-2-by-6 mm with seven slices, swallowing can be imaged in 3D real time at a frame rate of 12 fps.

Therapeutic neck dissection in head and neck melanoma patients: Comparing extent of surgery and clinical outcome in two cohorts.

BACKGROUND: The extent of surgical management of regional lymph nodes in the treatment of cutaneous head and neck melanoma on and anterior to O'Brien's watershed line is controversial. By comparing patients' cohorts of two separate melanoma expert centers we investigate the effectiveness of comprehensive versus (super-) selective neck dissection approach. METHODS: Sixty patients with macroscopic (palpable) neck node metastases (N2b) from anterior scalp and face melanoma were retrospectively studied. Forty therapeutic modified radical neck dissections (MRND; levels I-V) combined with elective parotidectomy from The Netherlands Cancer Institute (NCI) were compared with 16 (super-) selective neck dissections [(S)SND; 3-4 levels] and 4 solely MRNDs from Erasmus Medical Center (EMC). Cohorts were analyzed for site of recurrence, overall survival (OS), melanoma-specific survival (MSS), and disease-free survival (DFS). RESULTS: Clinical characteristics of patients were equal in both groups. In the NCI cohort 62.5% (n = 25) of patients recurred versus 65% (n = 13) in the EMC cohort. None of the NCI recurrences affected the parotid gland in contrast to 3 patients in the EMC group. Survival characteristics were not different between the two groups: OS (p = 0.56), MSS (p = 0.98), DFS (p = 0.92). CONCLUSION: This study does not support to continue the practice of routine elective parotidectomy and MRND in melanoma patients undergoing a lymph node dissection for macroscopic (palpable) nodal disease and justifies (S)SND.

Transtympanic Sodium Thiosulfate for Prevention of Cisplatin-Induced Ototoxicity: A Randomized Clinical Trial.

OBJECTIVES: To determine safety, feasibility, and preliminary activity of transtympanic injection of sodium thiosulfate (STS) against cisplatin-induced hearing loss (CIHL).DESIGN Randomized controlled trial.SETTING Tertiary cancer hospital.PATIENTS Adults to be treated with high-dose cisplatin (≥ 75 mg/m2).INTERVENTION Selected by randomization, 0.1 M STS gel on one side and placebo gel on the other side was transtympanically applied to the middle ear 3 hours before cisplatin administration. After amendment, the placebo ear was left untreated. MAIN OUTCOME MEASURE: Primary outcome was safety and feasibility. Secondary outcomes included pharmacokinetic analysis of systemic cisplatin and preliminary activity of STS. Clinically relevant CIHL was defined as a ≥ 10 dB threshold shift at pure-tone average 8-10-12.5 kHz (PTA8-12.5). Response to STS was defined as a threshold shift at PTA8-12.5 in the STS-treated ear of ≥ 10 dB smaller than the untreated ear. RESULTS: Twelve patients were treated. Average CIHL at PTA8-12.5 was 12.7 dB in untreated ears and 8.8 dB SPL in STS-treated ears (p = 0.403). Four patients did not develop CIHL. Four out of eight patients with CIHL responded to STS: CIHL at PTA8-12.5 in STS-treated ears was 18.4 dB less compared to untreated ears (p = 0.068). Grade 1 adverse events were reported. Pharmacokinetic results were available for 11 patients. CONCLUSION: Transtympanic application of STS was safe and feasible. Based on our pharmacokinetic analysis, we postulate that transtympanic STS does not interfere with the systemically available cisplatin. Our results provide a preliminary proof of concept for transtympanic application of STS in preventing CIHL and warrants further evaluation on a larger scale.

Technologic (R)Evolution Leads to Detection of More Sentinel Nodes in Patients with Melanoma in the Head and Neck Region.

Sentinel lymph node (SN) biopsy (SNB) has proven to be a valuable tool for staging melanoma patients. Since its introduction in the early 1990s, this procedure has undergone several technologic refinements, including the introduction of SPECT/CT, as well as radioguidance and fluorescence guidance. The purpose of the current study was to evaluate the effect of this technologic evolution on SNB in the head and neck region. The primary endpoint was the false-negative (FN) rate. Secondary endpoints were number of harvested SNs, overall operation time, operation time per harvested SN, and postoperative complications. Methods: A retrospective database was queried for cutaneous head and neck melanoma patients who underwent SNB at The Netherlands Cancer Institute between 1993 and 2016. The implementation of new detection techniques was divided into 4 groups: 1993-2005, with preoperative lymphoscintigraphy and intraoperative use of both a γ-ray detection probe and patent blue (n = 30); 2006-2007, with addition of preoperative road maps based on SPECT/CT (n = 15); 2008-2009, with intraoperative use of a portable γ-camera (n = 40); and 2010-2016, with addition of near-infrared fluorescence guidance (n = 192). Results: In total, 277 patients were included. At least 1 SN was identified in all patients. A tumor-positive SN was found in 59 patients (21.3%): 10 in group 1 (33.3%), 3 in group 2 (20.0%), 6 in group 3 (15.0%), and 40 in group 4 (20.8%). Regional recurrences in patients with tumor-negative SNs resulted in an overall FN rate of 11.9% (group 1, 16.7%; group 2, 0%; group 3, 14.3%; group 4, 11.1%). The number of harvested nodes increased with advancing technologies (P = 0.003), whereas Breslow thickness and operation time per harvested SN decreased (P = 0.003 and P = 0.017, respectively). There was no significant difference in percentage of tumor-positive SNs, overall operation time, and complication rate between the different groups. Conclusion: The use of advanced detection technologies led to a higher number of identified SNs without an increase in overall operation time, possibly indicating an improved surgical efficiency. Operation time per harvested SN decreased; the average FN rate remained 11.9% and was unchanged over 23 y. There was no significant change in postoperative complication rate.

Risk of breast cancer in women after a salivary gland carcinoma or pleomorphic adenoma in the Netherlands.

Salivary and mammary gland tumors show morphological similarities and share various characteristics, including frequent overexpression of hormone receptors and female preponderance. Although this may suggest a common etiology, it remains unclear whether patients with a salivary gland tumor carry an increased risk of breast cancer (BC). Our purpose was to determine the risk of BC in women diagnosed with salivary gland carcinoma (SGC) or pleomorphic adenoma (SGPA). BC incidence (invasive and in situ) was assessed in two nationwide cohorts: one comprising 1567 women diagnosed with SGC and one with 2083 women with SGPA. BC incidence was compared with general population rates using standardized incidence ratio (SIR). BC risk was assessed according to age at SGC/SGPA diagnosis, follow-up time and (for SGC patients) histological subtype. The mean follow-up was 7.0 years after SGC and 9.9 after SGPA diagnosis. During follow-up, 52 patients with SGC and 74 patients with SGPA developed BC. The median time to BC was 6 years after SGC and 7 after SGPA. The cumulative risk at 10 years of follow-up was 3.1% after SGC and 3.5% after SGPA (95% Confidence Interval (95%CI) 2.1%-4.7% and 2.6%-4.6%, respectively). BC incidence was 1.59 times (95%CI 1.19-2.09) higher in the SGC-cohort than expected based on incidence rates in the general population. SGPA-patients showed a 1.48 times (95%CI 1.16-1.86) higher incidence. Women with SGC or SGPA have a slightly increased risk of BC. The magnitude of risk justifies raising awareness, but is no reason for BC screening.

Handheld reflectance confocal microscopy: Personalized and accurate presurgical delineation of lentigo maligna (melanoma).

BACKGROUND: The surgical treatment of lentigo maligna melanoma is associated with high rates of local recurrence. Handheld reflectance confocal microscopy (HH-RCM) allows for in vivo presurgical detection of subclinical lentigo maligna (melanoma) (LM/LMM). METHODS: A single-center retrospective study from December 2015 to July 2017. Frequency and extent of negative surgical margins, and the diagnostic accuracy of presurgical mapping by HH-RCM was determined. RESULTS: Twenty-six consecutive patients with LM/LMM were included. In 45.8%, HH-RCM detected subclinical LM with a sensitivity of 0.90 and specificity of 0.86. The management was changed in two (7.7%) patients. Of the 24 remaining lesions, 95.8% were excised with negative margins with a mean histological margin of 3.1 and 5.3 mm for LM and LMM, respectively. At a mean follow-up of 36.7 months, there was one (4.8%) confirmed recurrence. CONCLUSIONS: Our method of presurgical delineation by HH-RCM appears to provide a reliable method for the surgical treatment of LM/LMM with a limited rate of overtreatment.

Five Specific Tongue Movements in a Healthy Population.

The importance of tongue mobility on speech, oral food transport, and swallowing is well recognized. However, whether the individual tongue mobility influences postoperative function in oral cancer treatment remains to be elucidated. This study assesses the ability to perform five tongue movements as rolling, twisting (two sides), folding, and the 'cloverleaf' in a healthy population. Because a tumor in oral cancer patients often restricts the mobility of the tongue, it might be helpful to know if it is possible to recall any of those movements without demonstrating it. Two observers asked 387 Dutch healthy adults if they could perform one of the five specific tongue movements and were subsequently asked to demonstrate the five movements. The distribution in the Dutch population is: rolling: 83.7%, cloverleaf: 14.7%, folding: 27.5%, twisting left: 36.1% and twisting right: 35.6%. The percentage of people that can fold their tongue is almost ten times higher (3% versus 27.5%) than in previous research, and it was found that the ability to roll the tongue is not a prerequisite for folding of the tongue. A relationship between gender or right-handedness and the ability to perform certain tongue movements could not be found. Of the participants, 9.9% and 13.1% incorrectly assumed that they could demonstrate tongue rolling and cloverleaf. Tongue folding and twisting (left or right) were incorrectly assumed in 36.9%, 24.1%, and 25.4% of the cases. Rolling and cloverleaf are preferred for future prediction models because these movements are easy to recall without demonstrating.

The tubarial salivary glands: A potential new organ at risk for radiotherapy.

INTRODUCTION: The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission tomography/computed tomography with prostate-specific membrane antigen ligands (PSMA PET/CT). We aimed to elucidate the characteristics of this unknown entity and its potential clinical implications for radiotherapy. MATERIALS AND METHODS: The presence and configuration of the PSMA-positive area was evaluated in a retrospective cohort of consecutively scanned patients with prostate or urethral gland cancer (n = 100). Morphological and histological characteristics were assessed in a human cadaver study (n = 2). The effect of radiotherapy (RT) on salivation and swallowing was retrospectively investigated using prospectively collected clinical data from a cohort of head-neck cancer patients (n = 723). With multivariable logistic regression analysis, the association between radiotherapy (RT) dose and xerostomia or dysphagia was evaluated. RESULTS: All 100 patients demonstrated a demarcated bilateral PSMA-positive area (average length 4 cm). Histology and 3D reconstruction confirmed the presence of PSMA-expressing, predominantly mucous glands with multiple draining ducts, predominantly near the torus tubarius. In the head-neck cancer patients, the mean RT dose to the gland area was significantly associated with physician-rated post-treatment xerostomia and dysphagia ≥ grade 2 at 12 months (0.019/gy, 95%CI 0.005-0.033, p = .007; 0.016/gy, 95%CI 0.001-0.031, p = .036). Follow-up at 24 months had similar results. CONCLUSION: The human body contains a pair of previously overlooked and clinically relevant macroscopic salivary gland locations, for which we propose the name tubarial glands. Sparing these glands in patients receiving RT may provide an opportunity to improve their quality of life.

A 12-channel flexible receiver coil for accelerated tongue imaging.

OBJECTIVE: MRI of the tongue requires acceleration to minimise motion artefacts and to facilitate real-time imaging of swallowing. To accelerate tongue MRI, we designed a dedicated flexible receiver coil. MATERIALS AND METHODS: We designed a flexible 12-channel receiver coil for tongue MRI at 3T and compared it to a conventional head-and-neck coil regarding SNR and g-factor. Furthermore, two accelerated imaging techniques were evaluated using both coils: multiband (MB) diffusion-tensor imaging (DTI) and real-time MRI of swallowing. RESULTS: The flexible coil had significantly higher SNR in the anterior (2.1 times higher, P = 0.002) and posterior (2.0 times higher, P < 0.001) parts of the tongue, while the g-factor was lower at higher acceleration. Unlike for the flexible coil, the apparent diffusion coefficient (P = 0.001) and fractional anisotropy (P = 0.008) deteriorated significantly while using the conventional coil after accelerating DTI with MB. The image quality of real-time MRI of swallowing was significantly better for hyoid elevation (P = 0.029) using the flexible coil. CONCLUSION: Facilitated by higher SNR and lower g-factor values, our flexible tongue coil allows faster imaging, which was successfully demonstrated in MB DTI and real-time MRI of swallowing.

Surgical site complications after parotid gland surgery for benign tumors in a centralized setting: A Clavien-Dindo class cohort analysis.

BACKGROUND: Surgical resection is the standard of care for parotid gland tumors. Comprehensive reports on the surgical complications of parotidectomy are lacking. This study focuses on surgical wound complications of parotid gland surgery. PATIENTS AND METHODS: In the period 2002-2012, 390 consecutive patients (395 procedures) who underwent parotid gland surgery were selected for retrospective analysis. Based on subsequent management, the impact of surgical site complications was graded by the Clavien-Dindo Classification (CDC). RESULTS: In 83 (21.0%) of the procedures, at least one complication was registered. In total, 118 complications were described. Rated to CDC, 61 patients (15.4%) were graded as class 2 or higher. This implies therapy was dictated. Fortyfive (11.4%) of the complications were surgical site infections (SSI). In 9 patients (2.3%) surgical complications required a surgical intervention under general anesthesia (CDC class 3b), and in 19 patients (4.8%) other invasive treatment (CDC class 3a) was needed. CONCLUSIONS: The Clavien-Dindo Classification proved to be very useful for retrospective registration of surgical complications. Of the 61 patients, 33 were managed by conservative therapy. No risk profile was found for patients at risk for direct surgical complications.

Sensorineural Hearing Loss After Adoptive Cell Immunotherapy for Melanoma Using MART-1 Specific T Cells: A Case Report and Its Pathophysiology.

OBJECTIVE: To illustrate a case of sensorineural hearing loss (SNHL) after immunotherapy based on T cell receptor (TCR) gene therapy using modified T cells recognizing melanoma antigen recognized by T cells 1 for disseminated melanoma. PATIENT: We present a 59-year-old woman with profound subacute bilateral SNHL including unilateral deafness after immunotherapy based on TCR gene therapy using modified T cells recognizing melanoma antigen recognized by T cells 1 for disseminated melanoma. Ten days after treatment, the patient developed hearing loss of 57 dB hearing loss air conduction at pure-tone average 0.5-1-2-4 kHz in the right ear, and >100 dB hearing loss air conduction at pure-tone average 0.5-1-2-4 in the left ear. The right ear recovered partially, while the left ear remained deaf, despite oral prednisolone (1.0 mg/kg) and salvage treatment with three transtympanic injections of 0.5 ml dexamethasone (4.0 mg/ml). CONCLUSION: Based on our presented case and a vast amount of literature there is circumstantial evidence that TCR gene therapy for melanoma targets the perivascular macrophage-like melanocytes in the stria vascularis, resulting in SNHL. We suggest that SNHL after TCR gene therapy may be caused by a disruption of the blood-labyrinth-barrier and the endolymphatic potential and/or a sterile inflammation of the stria vascularis. In severe cases like our subject, we posit that endolymphatic hydrops or hair cell loss may cause irreversible and asymmetrical deafness. Steroid prophylaxis via transtympanic application is debatable.

Parotidectomy in patients with head and neck cutaneous melanoma with cervical lymph node involvement.

BACKGROUND: Parotidectomy in melanoma of the coronal scalp and face with clinically involved cervical lymph node metastasis is based on predicted cervical lymphatic drainage described by O'Brien. METHODS: In total, 40 parotidectomies with en bloc therapeutic neck dissection were retrospectively analyzed. RESULTS: Lymphatic spread of melanoma to the parotid lymph nodes was observed in 10 of 40 specimens (25%). Eight of the 10 parotid-positive patients developed a recurrence vs 17 of the 30 parotid-negative patients (P = 0.28). There were no differences in overall survival, melanoma-specific survival, and disease-free survival between the parotid-positive and parotid-negative patients. CONCLUSION: Although in this series no survival differences were found, parotidectomy still merits a sustained role in therapeutic neck dissection procedures to improve regional control and to prevent facial nerve damage after surgery for a second relapse from occult metastases in the parotid.

Crossing muscle fibers of the human tongue resolved in vivo using constrained spherical deconvolution.

BACKGROUND: Surgical resection of tongue cancer may impair swallowing and speech. Knowledge of tongue muscle architecture affected by the resection could aid in patient counseling. Diffusion tensor imaging (DTI) enables reconstructions of muscle architecture in vivo. Reconstructing crossing fibers in the tongue requires a higher-order diffusion model. PURPOSE: To develop a clinically feasible diffusion imaging protocol, which facilitates both DTI and constrained spherical deconvolution (CSD) reconstructions of tongue muscle architecture in vivo. STUDY TYPE: Cross-sectional study. SUBJECTS/SPECIMEN: One ex vivo bovine tongue resected en bloc from mandible to hyoid bone. Ten healthy volunteers (mean age 25.5 years; range 21-34 years; four female). FIELD STRENGTH/SEQUENCE: Diffusion-weighted echo planar imaging at 3 T using a high-angular resolution diffusion imaging scheme acquired twice with opposing phase-encoding for B0 -field inhomogeneity correction. The scan of the healthy volunteers was divided into four parts, in between which the volunteers were allowed to swallow, resulting in a total acquisition time of 10 minutes. ASSESSMENT: The ability of resolving crossing muscle fibers using CSD was determined on the bovine tongue specimen. A reproducible response function was estimated and the optimal peak threshold was determined for the in vivo tongue. The quality of tractography of the in vivo tongue was graded by three experts. STATISTICAL TESTS: The within-subject coefficient of variance was calculated for the response function. The qualitative results of the grading of DTI and CSD tractography were analyzed using a multilevel proportional odds model. RESULTS: Fiber orientation distributions in the bovine tongue specimen showed that CSD was able to resolve crossing muscle fibers. The response function could be determined reproducibly in vivo. CSD tractography displayed significantly improved tractography compared with DTI tractography (P = 0.015). DATA CONCLUSION: The 10-minute diffusion imaging protocol facilitates CSD fiber tracking with improved reconstructions of crossing tongue muscle fibers compared with DTI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:96-105.

Inter-observer variation in the histopathology reports of head and neck melanoma; a comparison between the seventh and eighth edition of the AJCC staging system.

BACKGROUND: TNM staging of melanoma has recently been altered by the introduction of the 8th edition of the AJCC Cancer Staging manual. The purpose of this study is to analyze the inter-observer variation of histopathology reports and its effect on recommended treatment policy. METHODS: We retrospectively analyzed 296 cases, diagnosed as primary cutaneous head and neck melanoma (2005-2016), referred to the Netherlands Cancer Institute (NCI) for treatment after prior diagnosis in another hospital (non-NCI). All reports were analyzed for patients demographics, tumor characteristics and histopathologic features. RESULTS: In 53% and 40% of the cases, the histopathologic parameters were discordant, according to AJCC 7th and 8th edition, respectively. This indicated a perfect inter-observer agreement for the measurement of Breslow thickness (Intraclass correlation coefficient (ICC) = 0.981) and a substantial agreement for subtype (kappa statistic (κ) = 0.648) and ulceration (κ = 0.802), while only moderate for dermal mitotic activity (κ = 0.472). After NCI review, recommended treatment policies were changed in 13% and 11% of the patients when applying TNM 7 and TNM 8, respectively. Scheduling sentinel lymph node biopsy (SLNB) changed in 14 (5%) and 10 (3%) cases when using TNM 7 and TNM 8, respectively. CONCLUSION: Review by a NCI pathologist of histopathologic parameters of primary cutaneous head and neck melanoma led to significant changes in treatment decision. Introduction of the AJCC 8th edition led to slightly less discordances between NCI and non-NCI reports and consequently smaller impact on treatment planning. Expert review remains indicated when a SLNB is considered for additional staging in selected cases.

Psychosocial well-being of long-term survivors of pediatric head-neck rhabdomyosarcoma.

BACKGROUND: Head and neck rhabdomyosarcoma (HNRMS) survivors are at risk to develop adverse events (AEs). The impact of these AEs on psychosocial well-being is unclear. We aimed to assess psychosocial well-being of HNRMS survivors and examine whether psychosocial outcomes were associated with burden of therapy. PROCEDURE: Sixty-five HNRMS survivors (median follow-up: 11.5 years), treated in the Netherlands and the United Kingdom between 1990 and 2010 and alive ≥2 years after treatment visited the outpatient multidisciplinary follow-up clinic once, in which AEs were scored based on a predefined list according to the Common Terminology Criteria for Adverse Events. Survivors were asked to complete questionnaires on health-related quality of life (HRQoL; PedsQL and YQOL-FD), self-perception (KIDSCREEN), and satisfaction with appearances (SWA). HRQoL and self-perception scores were compared with reference values, and the correlation between physician-assessed AEs and psychosocial well-being was assessed. RESULTS: HNRMS survivors showed significantly lower scores on PedsQL school/work domain (P ≤ 0.01, P = 0.02, respectively), YQOL-FD domains negative self-image and positive consequences (P ≤ 0.01, P = 0.04, respectively) compared with norm data; scores on negative consequences domain were significantly higher (P = 0.03). Over 50% of survivors negatively rated their appearances on three or more items. Burden of AEs was not associated with generic HRQoL and self-perception scores, but was associated with disease-specific QoL (YQOL-FD). CONCLUSION: In general, HRQoL in HNRMS survivors was comparable to reference groups; however, survivors did report disease-specific consequences. We therefore recommend including specific questionnaires related to difficulties with facial appearance in a systematic monitoring program to determine the necessity for tailored care.

Three-Dimensional Tumor Margin Demarcation Using the Hybrid Tracer Indocyanine Green-99mTc-Nanocolloid: A Proof-of-Concept Study in Tongue Cancer Patients Scheduled for Sentinel Node Biopsy.

For radical resection of squamous cell carcinoma of the oral cavity, a tumor-free margin of at least 5 mm is required. Unfortunately, establishing in-depth margins is a surgical conundrum. Knowing that the hybrid sentinel node (SN) tracer indocyanine green (ICG)-99mTc-nanocolloid generates temporary tattoolike markings at the site of administration, we studied the ability to apply this tracer for tumor margin demarcation combined with SN biopsy. Methods: Nineteen patients with clinical T1-T2 oral tongue tumors received the traditional superficial 3 or 4 deposits of ICG-99mTc-nanocolloid (0.1 mL each), and in 12 patients additional deposits were placed deeply using ultrasound guidance (total of 6; 0.07 mL each). SN mapping was performed using lymphoscintigraphy and SPECT/CT. Before and directly after tumor excision, fluorescence imaging was performed to monitor the tracer deposits in the patient (fluorescent deposits were not used to guide the surgical excision). At pathologic examination, primary tumor samples were studied in detail. Results: The number of tracer depositions did not induce a significant difference in the number of SNs visualized (P = 0.836). Reproducible and deep tracer deposition proved to be challenging. The fluorescent nature of ICG-99mTc-nanocolloid supported in vivo and ex vivo identification of the tracer deposits surrounding the tumor. Pathologic examination indicated that in 66.7% (8/12), all fluorescence was observed within the resection margins. Conclusion: This study indicates that tumor margin demarcation combined with SN identification has potential but that some practical challenges need to be overcome if this technique is to mature as a surgical guidance concept. Future studies need to define whether the technology can improve the radical nature of the resections.

Simulation of facial expressions using person-specific sEMG signals controlling a biomechanical face model.

PURPOSE: Functional inoperability in advanced oral cancer is difficult to assess preoperatively. To assess functions of lips and tongue, biomechanical models are required. Apart from adjusting generic models to individual anatomy, muscle activation patterns (MAPs) driving patient-specific functional movements are necessary to predict remaining functional outcome. We aim to evaluate how volunteer-specific MAPs derived from surface electromyographic (sEMG) signals control a biomechanical face model. METHODS: Muscle activity of seven facial muscles in six volunteers was measured bilaterally with sEMG. A triple camera set-up recorded 3D lip movement. The generic face model in ArtiSynth was adapted to our needs. We controlled the model using the volunteer-specific MAPs. Three activation strategies were tested: activating all muscles [Formula: see text], selecting the three muscles showing highest muscle activity bilaterally [Formula: see text]-this was calculated by taking the mean of left and right muscles and then selecting the three with highest variance-and activating the muscles considered most relevant per instruction [Formula: see text], bilaterally. The model's lip movement was compared to the actual lip movement performed by the volunteers, using 3D correlation coefficients [Formula: see text]. RESULTS: The correlation coefficient between simulations and measurements with [Formula: see text] resulted in a median [Formula: see text] of 0.77. [Formula: see text] had a median [Formula: see text] of 0.78, whereas with [Formula: see text] the median [Formula: see text] decreased to 0.45. CONCLUSION: We demonstrated that MAPs derived from noninvasive sEMG measurements can control movement of the lips in a generic finite element face model with a median [Formula: see text] of 0.78. Ultimately, this is important to show the patient-specific residual movement using the patient's own MAPs. When the required treatment tools and personalisation techniques for geometry and anatomy become available, this may enable surgeons to test the functional results of wedge excisions for lip cancer in a virtual environment and to weigh surgery versus organ-sparing radiotherapy or photodynamic therapy.