Cost of Illness of Head and Neck Cancer in Sweden.

OBJECTIVES: Head and neck cancer (HNC) is the sixth most common cancer worldwide. The condition and its treatment often lead to marked morbidities and, for some patients, premature death. Inferentially, HNC imposes a significant economic burden on society. This study aims to provide a comprehensive and detailed estimation of the cost of illness of HNC for Sweden in 2019. METHODS: This is a prevalence-based cost of illness study. Resource utilization and related costs are quantified using national registry data. A societal perspective is applied, including (1) direct costs for healthcare utilization, (2) costs for informal care from family and friends, and (3) costs for productivity loss due to morbidity and premature death. The human capital approach is used when estimating productivity losses. RESULTS: The societal cost of HNC for Sweden in 2019 was estimated at €92 million, of which the direct costs, costs for informal care, and costs for productivity loss represented 34%, 2%, and 64%, respectively. Oral cavity cancer was the costliest HNC, followed by oropharyngeal cancer, whereas nasopharyngeal cancer was the costliest per person. The cost of premature mortality comprised 60% of the total cost of productivity loss. Males accounted for 65% of direct costs and 67% of costs for productivity loss. CONCLUSIONS: The societal cost of HNC is substantial and constitutes a considerable burden to Swedish society. The results of the present study may be used by policymakers for planning and allocation of resources. Furthermore, the information may be used for future cost-effectiveness analyses.

BioMEL: a translational research biobank of melanocytic lesions and melanoma.

INTRODUCTION: Diagnosing invasive cutaneous melanoma (CM) can be challenging due to subjectivity in distinguishing equivocal nevi, melanoma in situ and thin CMs. The underlying molecular mechanisms of progression from nevus to melanoma must be better understood. Identifying biomarkers for treatment response, diagnostics and prognostics is crucial. Using biomedical data from biobanks and population-based healthcare data, translational research can improve patient care by implementing evidence-based findings. The BioMEL biobank is a prospective, multicentre, large-scale biomedical database on equivocal nevi and all stages of primary melanoma to metastases. Its purpose is to serve as a translational resource, enabling researchers to uncover objective molecular, genotypic, phenotypic and structural differences in nevi and all stages of melanoma. The main objective is to leverage BioMEL to significantly improve diagnostics, prognostics and therapy outcomes of patients with melanoma. METHODS AND ANALYSIS: The BioMEL biobank contains biological samples, epidemiological information and medical data from adult patients who receive routine care for melanoma. BioMEL is focused on primary and metastatic melanoma, but equivocal pigmented lesions such as clinically atypical nevi and melanoma in situ are also included. BioMEL data are gathered by questionnaires, blood sampling, tumour imaging, tissue sampling, medical records and histopathological reports. ETHICS AND DISSEMINATION: The BioMEL biobank project is approved by the national Swedish Ethical Review Authority (Dnr. 2013/101, 2013/339, 2020/00469, 2021/01432 and 2022/02421-02). The datasets generated are not publicly available due to regulations related to the ethical review authority. TRIAL REGISTRATION NUMBER: NCT05446155.

Predictors of survival in advanced oral cancers after salvage surgery with free tissue flap reconstruction.

OBJECTIVE: To identify prognostic factors for patients with advanced persistent, recurrent, or 2nd primary oral cavity squamous cell carcinoma (OCSCC) potentially unsuitable for salvage surgery with free tissue flap (FTF) reconstruction. MATERIALS AND METHODS: A population-based cohort of 83 consecutive patients with advanced OCSCC who underwent salvage surgery with FTF reconstruction at a tertiary referral centre between 1990 and 2017. Retrospective uni- and multivariable analyses were performed to identify factors affecting all-cause mortality (ACM), i.e., overall survival (OS), as well as disease-specific mortality (DSM), i.e., disease-specific survival (DSS) after salvage surgery. RESULTS: Median disease-free interval until recurrence was 15 months with recurrent stage I/II in 31% and III/IV in 69%. Median age at salvage surgery was 67 years (range 31-87) and the median follow-up (alive patients) 126 months. At 2, 5, and 10 years after salvage surgery, respectively, DSS rates were 61%, 44%, and 37% and OS rates 52%, 30%, and 22%. Median DSS was 26 and OS 43 months. Multivariable analysis identified recurrent clinical regional (cN-plus) disease [HR 3.57; p < .001] and elevated gamma-glutamyl transferase (GGT) [HR 3.30; p = .003] as independent pre-salvage predictors for poor OS after salvage, whereas initial cN-plus [HR 2.07; p = .039] and recurrent cN-plus disease [HR 5.14; p < .001] predicted poor DSS. Among post-salvage factors, extranodal extension according to histopathology [HR ACM 6.11; HR DSM 9.99; p < .001] as well as positive [HR ACM 4.98; DSM 7.51; p < 0.001] and narrow surgical margins [HR ACM 2.12; DSM HR 2.80; p < 0.01] emerged as independent factors for poor survival. CONCLUSION: While salvage surgery with FTF reconstruction is the primary curative option for patients with advanced recurrent OCSCC, the present findings may help guide discussions with patients who have advanced recurrent regional disease and high GGT preoperatively, especially if there is a small chance of reaching surgical radicality.

Outcome for sinonasal malignancies: a population-based survey.

PURPOSE: Sinonasal malignancies (SNM) represent a rare and complex group of cancers that includes a wide range of histopathological subtypes. Data from population-based cohorts are scarce but warranted as a basis for randomized controlled treatment trials (RCTs). Our aim was to assess overall and histology subset-specific outcomes for SNM patients treated at a tertiary referral centre. METHODS: A retrospective, population-based, consecutive cohort of patients with SNMs diagnosed from 2001 through 2019 was examined. Outcome was analysed in relation to age, gender, site, stage, histopathology, and treatment. RESULTS: Two-hundred and twenty-six patients were identified, whereof 61% presented with stage IV disease. 80% completed treatment with curative intent, which comprised surgery with neoadjuvant (29%) or adjuvant (37%) radiotherapy, monotherapy with surgery (22%), definitive chemoradiotherapy (7%), or radiotherapy (5%). Median follow-up was 106 months. The 5- and 10-year overall survival rates were 57% and 35%, respectively. Median overall survival was 76 months (esthesioneuroblastoma: 147 months; adenocarcinoma: 117; salivary carcinoma: 88; mucosal melanoma: 69; squamous cell carcinoma: 51, undifferentiated carcinoma: 42; neuroendocrine carcinoma: 9; and NUT-carcinoma 5). The 5- and 10-year disease-free survival rates were 63% and 54%, respectively, and disease-specific survival 83% and 66%. Increasing age, stage IVB, melanoma histopathology, and treatment with definitive chemoradiotherapy emerged as significant independent prognostic risk factors for disease-specific mortality (p ≤ 0.001). CONCLUSION: The results indicate a seemingly good outcome in comparison to previous reports, particularly for mucosal melanoma, adenocarcinoma, and undifferentiated carcinoma. The study provides additional background for future RCTs focusing on histology subset-specific treatment for SNM.

Scapular osseous free flap in head and neck reconstruction: An assessment of the postoperative function of the donor site.

BACKGROUND: The scapular osseous free flap (SOFF) has become an important reconstructive option for complex head and neck defects. Postoperative donor site function is, however, an important consideration. The objective of this study was to prospectively investigate SOFF donor site morbidity and to relate the findings to hand dominance and neck dissection. METHODS: Objective assessment included bilateral measurement of shoulder, elbow, and hand range of motion (ROM), hand strength, and distal nerve function in consecutive patients with head and neck cancer SOFF reconstruction at a tertiary referral center in Sweden between 2016 and 2019. The subjective function was assessed by the Disability of the Arm, Shoulder and Hand (DASH) questionnaire. RESULTS: Sixteen of 20 consecutive patients were evaluated (median follow-up 10 months [range 3-17]). Significant side differences in shoulder range of motion (ROM) (flexion, abduction, external and internal rotation) were observed for patients where the SOFF had been harvested from the same side as their dominant hand (n = 9; Ps ≤ 0.04). For patients where the SOFF was harvested from the non-dominant hand side, no significant shoulder ROM side differences were observed (n = 7; Ps ≥ 0.08). There were significant side differences in shoulder ROM for patients who underwent neck dissections (n = 12; Ps ≤ 0.03), not for the other four patients. Patients reported low but varying DASH scores (median 2.5, range 0-57). CONCLUSION: Postoperative donor site morbidity seems to be quite acceptable after SOFF surgery. The results indicate possible benefits of choosing the non-dominant hand side for the SOFF and that a neck dissection affects postoperative shoulder outcome. Further studies are however needed.

Non-radical primary diagnostic biopsies affect survival in cutaneous head and neck melanoma.

BACKGROUND: It is unclear if a non-radical diagnostic biopsy entails a higher risk for metastasis and poorer survival for patients with cutaneous head and neck melanoma (cHNM). AIMS/OBJECTIVES: To assess whether or not initial diagnostic biopsy modality and radicality (clear, positive, or narrow histopathological margins) influence recurrence and survival in patients with cHNM. MATERIALS AND METHODS: Histopathological radicality of initial diagnostic biopsies and outcome for 368 consecutive cHNM patients, clinically asymptomatic of metastatic disease and referred to a tertiary care academic center for sentinel lymph node staging from 2004 through 2018, were retrospectively analyzed. RESULTS: Patients with positive (n = 133) or narrow (0.1-0.5 mm) (n = 34) histopathological margins had significantly worse loco-regional (p=.004) and distant control (p=.004) as well as lower overall (p=.017) and melanoma specific (p=.0002) survival than 201 patients with clear margins. Multivariate analysis indicated positive or narrow histopathological margins as independent negative prognostic factors for melanoma specific survival (HR 2.16, p=.015), together with deeper Breslow (HR 1.17, p=.00001) and ulceration (HR 2.49, p=.003). CONCLUSIONS AND SIGNIFICANCE: Non-radical primary diagnostic biopsies increase the risk for metastatic disease and impair survival in cHNM. Accordingly, radical melanoma diagnostic procedures should be encouraged in the head and neck region when possible.

Patients with cutaneous head and neck melanoma, particularly elderly with more advanced primary tumors, seem to benefit from initial CT staging before considering a sentinel lymph node biopsy.

Background: The role of CT scanning at the time of diagnosis for patients with primary cutaneous head and neck melanoma (cHNM) clinically asymptomatic for metastatic disease remains unclear.Aim: To determine the positive yield of initial CT scanning before considering sentinel lymph node biopsy (SLNB) staging.Materials and methods: A retrospective review was performed on 170 consecutive patients with cHNM referred to a tertiary head and neck academic center for SLNBs from 2014 through 2018.Results: Initial CTs identified occult melanoma metastases in 7.1% and other advanced malignancies in 4.7%. The overall CT yield for patients >65 years (n = 115) was 13.9%, and 5.5% for patients <65 (only occult melanoma metastases). The SLNB yield did not differ between older (11.5%) and younger patients (10.2%). Patients with more advanced primary tumors were upstaged more often by both staging procedures. Multivariate analysis indicated a true-positive CT finding as the strongest prognostic factor for OS (p<.001).Conclusions and significance: The CT yield was >11% and higher for older than for younger patients. The findings suggest that CT imaging may be considered before SLNB staging, potentially identifying metastatic melanoma disease as well as other occult malignancies, enabling especially older patients to bypass the SLNB procedure.

Co-morbidities to Vestibular Impairments-Some Concomitant Disorders in Young and Older Adults.

Background: Dizziness and pain are common complaints that often appear concomitantly, with or without a causal relationship. However, these symptoms might maintain and exacerbate each other and other co-morbidities. Therefore, adequate rehabilitation may have to include an expanded focus on other deficits and preconditions, especially in older adults and in patients. Objective: To understand how frequently vestibular dysfunction coincided with medical conditions and aging, we studied two categories: Study 1: patients referred to a vestibular unit and Study 2: senior members in a fitness association. Method: Study 1: 49 patients [34 females/15 males; mean age 52 years (SEM 2.0)] seeking health care for balance disorders and vestibular deficits were asked in questionnaires about their perception of dizziness and pain, and emotional and functional strains. Study 2: 101 senior members in a fitness association [91 females/10 males; mean age 75 years (SEM 0.6)], were assessed for vestibular and balance deficits and for any co-morbidities. The participants were monitored for falls for 12 months after the initial assessments. Result: Study 1: Co-morbidity often existed between dizziness and pain (65%). The patients reported high emotional and functional strain related to their dizziness and pain. Patients older than 60 years reported longer durations of pain (p ≤ 0.028) but less emotional strain (p = 0.036), compared to younger patients. Study 2: 84% of the participants had a vestibular impairment, often without noticing any symptoms. Furthermore, 40% reported cardiovascular illnesses, 12% musculoskeletal disorders, and 63% reported other medical conditions. Forty-two percent experienced falls within 1 year after the initial assessments (thereof 42% in the group with vestibular deficits and 38% in the group without vestibular deficits). Conclusion: To enhance and preserve postural control, both in patients with vestibular deficits and in older adults, we suggest an expanded clinical perspective. Hence, we recommend detailed examinations of the vestibular system but simultaneously probing for possible co-morbidities. Since aging often entails deterioration of multimodal processes related to maintained mobility and postural stability, our results add focus on the importance of addressing balance disorders together with additional medical conditions.

Survival benefits from concomitant chemoradiotherapy before radical surgery in stage IVA sinonasal mucosal melanoma?

BACKGROUND: The aim of the study was to review a local treatment protocol for sinonasal mucosal melanoma (SNMM) focusing on triple modality treatment (TMT), that is, neoadjuvant concomitant chemoradiotherapy (CRT) and surgery. METHODS: In a retrospective design, data on clinical presentation, treatment, and survival were retrieved for 22 consecutive patients from a tertiary referral center. RESULTS: The mean overall survival (OS) for all patients (3 stage III, 16 stage IVA, and 3 stage IVB) was 62 months, and the 5-year OS rate 50%. Four of the 22 patients received treatment with palliative intention. Of the 18 patients who received treatment with curative intention, patients with stage IVA disease who received TMT (n = 10) had a 5-year OS of 70% and 10-year OS of 20%. The median disease-free survival for these patients was 51 months compared with 9 months for stage IVA not receiving TMT (n = 4). CONCLUSION: A seemingly favorable survival outcome for a disease with characteristically poor prognosis was observed. The lead finding was a high survival rate (70% 5-year OS) for stage IVA patients who received neoadjuvant TMT. The observations suggest the possibility that patients with advanced SNMM (stage IVA) might benefit from concomitant CRT before surgery by delaying the onset of local recurrences and distant metastases. LEVEL OF EVIDENCE: Level 4, case series (with or without comparison).

Low efficacy using the 256-Hz tuning fork when evaluating the influence of somatosensation in balance control for relatively healthy elderly.

BACKGROUND: Diminished foot somatosensation contributes to balance deficits and increased fall risk. However, it remains unclear if the 256-Hz tuning fork is adequate to measure, in the outpatient clinical setting, somatosensation in relatively healthy elderly. AIMS/OBJECTIVES: To evaluate the performance of the 256-Hz tuning fork compared to other measures of somatosensation and balance. MATERIAL AND METHODS: Thirty-six subjects (mean 69.4 ± 5.3 years) were allocated into four 256-Hz tuning fork sensation groups (TFSG) based on their ability to detect vibration at the first metatarsal, malleolus, tibia or no sites. A biothesiometer measured vibration perception thresholds (VPTs) and 20 monofilaments tactile pressure sensation thresholds (TPSTs). Balance was evaluated with posturography, functional balance tests and questionnaires. RESULTS: There were no significant differences in age, VPTs or TPSTs between the four TFSGs, nor in outcome of functional balance tests, posturography and questionnaires. Very few significant associations were found between TFSGs and VPTs, TPSTs, functional balance tests, posturography and questionnaires. CONCLUSIONS AND SIGNIFICANCE: Somatosensation measured with a 256-Hz tuning fork seems to be a minor determinant for balance and thus superfluous when evaluating the importance of vibration perception for balance control in relatively healthy elderly.

Perceived and Functional Balance Control Is Negatively Affected by Diminished Touch and Vibration Sensitivity in Relatively Healthy Older Adults and Elderly.

Background: Severe diminished foot somatosensation, for example, caused by neuropathies and advanced aging, contributes to balance deficits and increased fall risk. However, little is known about somatosensory impairment and functional and subjective balance problems in relatively healthy elderly. Method: Vibration perception thresholds (VPTs) were assessed with a biothesiometer and tactile pressure sensation thresholds (TPSTs) with 20 monofilaments in 34 relatively healthy community-dwelling older adults (M = 69.4 years). Balance was evaluated with functional balance tests and questionnaires. A stepwise regression analysis was performed to determine the extent to which VPTs, TPSTs, and age could explain balance impairments. Results: High VPTs had negative effects on Berg Balance Scale and Dizziness Handicap Inventory scores (p ≤ .011), as did high TPSTs on walking speed and Figure-8 test (p ≤ .001). With visual information available, one-leg standing time (OLST) was significantly affected by ipsilateral VPTs on solid and TPSTs on compliant surface (p ≤ .002). Without visual information, age was the only factor with a main effect on OLST (p < .001). Age had no significant correlations with TPSTs or VPTs. Discussion: Somatosensation appears to be very important for perceived as well as functional balance control in older adults. Our findings have important clinical implications when assessing balance impairment and impending fall risk.

Benefits of initial CT staging before sentinel lymph node biopsy in patients with head and neck cutaneous melanoma.

BACKGROUND: The value of CT at the time of diagnosis for patients with cutaneous head and neck melanoma clinically asymptomatic for metastatic disease is unclear. METHODS: A retrospective medical chart review was performed on 198 consecutive patients identified with primary T1b-T4b head and neck melanoma clinically asymptomatic for metastatic disease referred for sentinel lymph node biopsy procedures between 2004 and 2014. RESULTS: Initial CTs identified clinically occult melanoma metastases in 8.1% and advanced second primary tumors in 3.5% of patients. CT findings were false-negative in 1% and false-positive in 6% of patients. Overall survival (OS) for patients with true-positive CT findings was lower than for the other patients (P < .001). CONCLUSION: CT imaging when staging patients with head and neck melanoma seems to identify more metastases than has been reported for melanoma at other sites. Preoperative CTs decreased the number of sentinel lymph node biopsy (SLNBs), thus avoiding the stress and cost of this surgical procedure in 12% of patients.

Sentinel lymph node biopsy staging for cutaneous malignant melanoma of the head and neck.

Conclusion Sentinel lymph node biopsies (SLNBs) can be performed safely and with reasonable accuracy in HNM patients. The outcome provides important prognostic information concerning DFS and further treatment. However, one must recognize that SLNB is a multidisciplinary procedure with a learning curve for all. Objectives To evaluate efficacy of performing SLNBs in a series of consecutive patients with cutaneous head and neck melanoma (HNM) ≥ T1b from introduction of the procedure and 10 years onward. Method End-points comprised of SLNB outcome, disease-free survival (DFS), and overall survival (OS). Results SNs were harvested in 128 of 160 patients (median Breslow = 2.0 mm, 29% ulcerated); success rate = 80.0%, or 92.1% if excluding patients where SLNBs were omitted due to non-localization on pre-operative imaging or because of SN-location in the parotid basin. Ten patients (7.8%) had positive SLNBs and were offered early completion neck dissections. Of the 146 patients available for follow-up (median = 27 months), 15.8% had recurrent disease. The risk of a regional nodal recurrence after a negative SLNB was 7.5%. SN-negative patients had improved DFS c.f. SN-positive patients (p < 0.001). A positive SLNB was the most important prognostic predictor of decreased DFS (hazard ratio = 5.70; p < 0.005), but had no significant impact on OS.

Improved Balance Confidence and Stability for Elderly After 6 Weeks of a Multimodal Self-Administered Balance-Enhancing Exercise Program: A Randomized Single Arm Crossover Study.

Objective: To develop and assess the efficacy of a multimodal balance-enhancing exercise program (BEEP) designed to be regularly self-administered by community-dwelling elderly. The program aims to promote sensory reweighting, facilitate motor control, improve gaze stabilization, and stimulate continuous improvement by being constantly challenging. Method: Forty participants aged 60 to 80 years performed 6 weeks of BEEP training, on average for 16 min four times weekly, in a randomized one-arm crossover design. Results: One-leg standing time improved 32% with eyes open (EO), 206% with eyes closed (EC) on solid surface, and 54% EO on compliant surface (p < .001). Posturography confirmed balance improvements when perturbed on solid and compliant surfaces with EO and EC (p ≤ .033). Walking, step stool, and Timed Up and Go speeds increased (p ≤ .001), as did scores in Berg Balance and balance confidence scales (p ≤ .018). Discussion: Multimodal balance exercises offer an efficient, cost-effective way to improve balance control and confidence in elderly.

Increased visual dependence and otolith dysfunction with alcohol intoxication.

Alcohol intoxication affects the vestibular system and balance control in many ways. We have investigated how acute, moderate (blood alcohol concentrations of 0.06+/-0.01%), and high (0.10+/-0.02%) alcohol intoxication affects the ability to perceive the visual horizontal and vertical and the visual field dependence measured with the rod and frame tests in 24 healthy participants. Alcohol ingestion impaired the ability to use gravitational vestibular cues when determining the visual vertical and horizontal, and caused increased visual field dependence. With conflicting gravitational and visual information, alcohol seems to promote a reweighting in balance control from a vestibular to a more visual dependency. Furthermore, the results indicate that alcohol intoxication at these levels start instigating a decompensation of minute subclinical vestibular asymmetries.

Subjective visual tilt and lateral instability after vestibular deafferentation.

CONCLUSION: Defective utricular function, reflected by deviation of the perceived visual horizontal or vertical, cannot by itself explain increased postural sway in the lateral direction for patients with unilateral vestibular deafferentation (uVD). OBJECTIVE: It is not known why some patients with chronic uVD report distressing unsteadiness while others do not. The objective of this study was to test the hypothesis that impaired utricular compensation, reflected by pathologic tilt in the subjective visual horizontal and vertical (SVH-V) test, would affect postural control in the lateral direction after uVD. PATIENTS AND METHODS: The SVH-V was tested in 28 patients 6 months after translabyrinthine surgery for unilateral vestibular schwannoma, and correlated with posturography results. RESULTS: No increase in lateral and anterior-posterior sway, or the quotients between them, or for Romberg quotients, was found with increasing SVH-V tilt.

Ipsilesional visual field dependency for patients with vestibular schwannoma.

Vestibular schwannoma patients have a non-homogenous vestibular function and compensation, and might rely more on visual cues for balance control. Using the rod and frame test, visual field dependence was investigated in 17 patients with vestibular schwannoma who had a normal subjective visual horizontal and vertical (0.8 +/- 1.4 degrees). Findings were correlated with tumor size, age, and other parameters of vestibular compensation and compared with field dependency results of 28 healthy subjects. Vestibular schwannoma patients showed greater deviation in the rod and frame test when the frame was tilted towards the lesioned ear (mean 8.2 +/- 4.9 degrees), than towards the healthy ear (mean 5.5 +/- 6.0 degrees; p=0.013). The results indicate a unilateral visual field dependency for patients with vestibular schwannoma that predicts the lesioned side.

Idiosyncratic compensation of the subjective visual horizontal and vertical in 60 patients after unilateral vestibular deafferentation.

OBJECTIVE: To investigate long-term compensation mechanisms of utricular function after translabyrinthine surgery for vestibular schwannoma. Correlations between the subjective visual horizontal (SVH) and subjective visual vertical (SVV) and other parameters of vestibular compensation were studied. The correlation between the SVH and SVV was also investigated to see whether these measurements are compatible for patients. MATERIAL AND METHODS: Sixty consecutive patients were investigated 3 months before and 6 months after surgery by means of electronystagmography and SVH and SVV tests. Tumor size was measured using MRI. RESULTS: The SVH and SVV increased significantly towards the ipsilesional side postoperatively. Preoperative tilt correlated with age. Postoperative tilt correlated weakly with preoperative caloric sensitivity and inversely with tumor size. The correlation between the SVH and SVV was high both before and after surgery (r(s) > 0.74; p < 0.001). CONCLUSIONS: The long-term compensation of static tilt perception was dependent on age and not on dynamic canal functions. We propose an idiosyncrasy in the SVH and SVV compensation after unilateral vestibular deafferentation, incongruous with the general course of vestibular compensation. The results suggest a probable dependence on non-vestibular information, i.e. proprioception, in facilitating compensation of static vestibular deficits. The similarity between the SVH and SVV measurements confirms that either test can be used clinically for patients with vestibular lesions.