Laryngeal Subsites Research Articles

Comparative characteristics of laryngeal-resident mesenchymal stromal cell populations isolated from distinct sites in the rat larynx

BackgroundAlthough tissue-resident mesenchymal stromal cells (MSCs) in the larynx have been described, their distinct characteristics and roles have not been thoroughly explored. Therefore, we investigated stem cell characteristics and regenerative potentials of single clonal populations isolated from rat epiglottic mucosa (EM), lamina propria (LP), and macula flava (MF) to determine whether they comprised laryngeal tissue-resident stem cells.MethodsSingle clonal laryngeal cells were isolated following microdissection of the EM, LP, and MF from the rat larynx. Several clonal populations from the three laryngeal subsites were selected and expanded in vitro. We compared the stem cell characteristics of self-renewal and differentiation potential, as well as the cell surface phenotypes and gene expression profiles, of laryngeal MSC-like cells to that of bone marrow MSCs (BM-MSCs). We also investigated the regenerative potential of the laryngeal cells in a radiation-induced laryngeal injury animal model.ResultsSelf-renewing, clonal cell populations were obtained from rat EM, LP, and MF. EM-derived and LP-derived clonal cells had fibroblast-like features, while MF-resident clonal cells had stellate cell morphology and lipid droplets containing vitamin A. All laryngeal clonal cell populations had MSC-like cell surface marker expression (CD29, CD44, CD73, and CD90) and the potential to differentiate into bone and cartilage cell lineages; EM-derived and MF-derived cells, but not LP-derived cells, were also able to differentiate into adipocytes. Clonal cells isolated from the laryngeal subsites exhibited differential extracellular matrix-related gene expression. We found that the mesenchymal and stellate cell-related genes desmin and nestin were enriched in laryngeal MSC-like cells relative to BM-MSCs (P < 0.001). Growth differentiation factor 3 (GDF3) and glial fibrillary acidic protein (GFAP) transcript and protein levels were higher in MF-derived cells than in other laryngeal populations (P < 0.001). At 4 weeks after transplantation, laryngeal MF-derived and EM-derived cells contributed to laryngeal epithelial and/or glandular regeneration in response to radiation injury.ConclusionsThese results suggest that cell populations with MSC characteristics reside in the EM, LP, and MF of the larynx. Laryngeal MSC-like cells contribute to regeneration of the larynx following injury; further investigation is needed to clarify the differential roles of the populations in laryngeal tissue regeneration, as well as the clinical implications for the treatment of laryngeal disease.

Laryngeal distribution of recurrent respiratory papillomatosis in a previously untreated cohort.

To describe the distribution of recurrent respiratory papillomatosis (RRP) lesions across 21 laryngeal anatomic regions in previously untreated patients at initial presentation to provide insight regarding the natural history of RRP. Multi-institutional, retrospective case series. Initial laryngoscopic examination videos of 83 previously untreated patients with adult-onset RRP were reviewed. Papilloma locations were recorded using a 21-region laryngeal schematic. Multivariate analyses by anatomic subsite were conducted for the entire population and for subgroups stratified by sex, age, and proton pump inhibitor (PPI) usage. Heat maps were generated, hierarchically color coding the anatomic distribution of disease. In this cohort, RRP was most likely to occur on the true vocal folds (TVFs) and anterior commissure (P < .0001, odds ratio [OR]: 7.02); within the TVFs, the membranous vocal folds (MVFs) were most likely to be affected (P < .0001, OR: 3.56). The cohort was predominantly male (80.7%); males had a higher average number of affected sites (P = .005) and were more likely to have lesions in any laryngeal subsite (P < .0001, OR: 2.88,) compared to females. PPI users were more likely than nonusers to have disease in any laryngeal subsite (P = .0037, OR: 1.62), particularly in the posterior and subglottic regions (P = .0061, OR: 2.53). Age was not correlated with lesion prevalence or distribution. In untreated patients presenting to three laryngology clinics, the MVFs were most likely to be affected by RRP. Males had more anatomic sites affected by papilloma than females. The influence of PPI use on RRP distribution warrants further investigation. 4. Laryngoscope, 128:138-143, 2018.

Menstrual Cycle, Vocal Performance, and Laryngeal Vascular Appearance: An Observational Study on 17 Subjects

To assess the anatomical and functional features of the vocal folds during different phases of the female menstrual cycle. An observational study of 17 healthy fertile female volunteers not using hormonal contraception was carried out. Each volunteer underwent two examinations: first, during the early days of the menstrual cycle when progesterone levels are low (p-depletion), and second, during premenstruation when progesterone levels are high (p-peak). The workup included blood hormone levels, Voice Handicap Index, acoustic analysis, rigid telescopy, stroboscopy, and narrow band imaging. The videos were evaluated by blinded observers. The participants' mean age was 31.7 ± 5.6 (range 23-43). Progesterone levels were 13- to 45-fold higher in p-peak relative to p-depletion. No significant differences were detected in Voice Handicap Index scores, stroboscopic reports, or acoustic analysis between p-peak and p-depletion examinations. Analyzing the rigid telescopy and narrow band imaging videos, the observers tended to estimate the different laryngeal subsites more vascularized during the p-peak examination. Moreover, this tendency was significantly correlated with blood progesterone levels during the p-depletion examinations; the lower the blood progesterone levels were during p-depletion, the higher the probability for the observers to estimate the p-peak examinations more vascularized (P value = 0.024). Alterations in laryngeal vascular characteristics are evident throughout the menstrual cycle and may suggest increased congestion during premenstrual days. Variations in progesterone levels during the menstrual cycle correlate with laryngeal vascular changes. Hormone-related alterations in vocal folds' vascularity may have a role in the variability of vocal performance in certain women.

Serum cytokine profile of laryngeal squamous cell carcinoma patients.

This study aimed to evaluate serum cytokine concentrations in healthy individuals and laryngeal squamous cell carcinoma patients. A total of 59 laryngeal squamous cell carcinoma patients and 44 healthy controls were included. Multiplex analysis of interleukins 2, 4, 5, 6, 10, 12, 13 and 17 and interferon-gamma with respect to the presence of laryngeal carcinoma, tumour-node-metastasis T stage, nodal involvement and larynx subsite was performed. Statistical analysis revealed no difference in serum cytokine levels between patients and healthy controls. The serum interleukin-12 concentration was significantly higher in patients with early (T1-2) than in those with late (T3-4) stage disease and without nodal involvement (p < 0.05). Serum interleukin-10 levels were significantly higher in T3-4 stage than in T1-2 stage patients (p < 0.05). Additionally, serum interleukin 10, 12 and 13 concentrations (p < 0.05) and interleukin-6 concentration (p < 0.01) were significantly higher in patients with T1-2 stage supraglottic vs glottic tumours. Serum cytokines level cannot be used as laryngeal squamous cell carcinoma markers. Progression from T1-2 to T3-4 stage is followed by decreased serum interleukin-12 levels and increased interleukin-10 levels. Nodal involvement is associated with lower serum interleukin-12 levels. In patients with early stage tumours, serum interleukin 6, 10, 12 and 13 concentrations are significantly higher in those with supraglottic vs glottic tumours.

Effect of postoperative radiotherapy on survival for surgically managed pT3N0 and pT4aN0 laryngeal cancer: Analysis of the National Cancer Data Base.

The current study was conducted to determine the effect of postoperative radiotherapy (PORT) on overall survival in patients with surgically managed pT3-T4aN0 laryngeal squamous cell carcinoma (SCC). A review of the National Cancer Data Base from 2004 through 2013 was performed. Patients with surgically managed pT3-4aN0 laryngeal SCC with negative surgical margins were included. Univariable and multivariable Cox regression analyses were used to determine factors associated with survival. A total of 1460 patients were included, 46.2% of whom had pT3N0 disease (674 patients) and 53.8% of whom had pT4aN0 disease (786 patients). Approximately 72.0% of the patients with pT3N0 disease (485 patients) and 50.1% of the patients with pT4aN0 disease (394 patients) received PORT. PORT was not found to be associated with improved overall survival on univariable analysis for patients with pT3N0 disease (hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62-1.14), but was for patients with pT4aN0 disease (HR, 0.57; 95% CI, 0.45-0.71). For patients with pT3N0 SCC of the larynx, in a multivariable Cox regression analysis adjusting for age >65 years, severity of comorbidities, larynx subsite, extent of laryngectomy, and number of lymph nodes removed, PORT was not found to be associated with improved survival (adjusted HR, 0.88; 95% CI, 0.64-1.21). For patients with pT4aN0 disease, the administration of PORT was associated with improved survival on multivariable analysis adjusting for age >65 years, severity of comorbidities, larynx subsite, number of lymph nodes removed, and type of hospital (adjusted HR, 0.58; 95% CI, 0.46-0.73). For patients with surgically managed pT3N0 laryngeal SCC with negative margins, PORT does not appear to be associated with improved survival. Despite a survival benefit, nearly 50% of patients with pT4aN0 laryngeal SCC and negative surgical margins do not receive standard-of-care PORT. Cancer 2017;123:2248-2257. © 2017 American Cancer Society.

Identification of Anatomic Correlates of Failure in Patients With T4a Larynx Cancer

To identify whether anatomic patterns of primary tumor invasion in T4a laryngeal squamous cell carcinoma predict local control (LC) in patients treated with non-surgical larynx preservation (LP) approaches versus patients treated with total laryngectomy (followed by post-operative radiation therapy (TL-PORT)). We retrospectively reviewed the medical records of patients with T4a (AJCC 7th) squamous cell laryngeal cancer treated between 1983 to 2011 at a single institution Anatomic invasion by primary tumor of any combination of cartilage (cricoid or thyroid), muscles, or soft tissue (thyroid gland or esophagus) was recorded. Areas of invasion were then categorized by number of structures multiplicity such as single cartilage, muscle, or soft tissue versus multiple (e.g. cartilage and muscle/soft tissue), then grouped into a binary of single (SIP) or multiple invasion pattern (MIP). Kaplan-Meier and log-rank tests were used to evaluate LC. Cox regression multivariate analysis was performed. 220 patients with a median follow-up of 68 months were analyzed. 60 (27%) received LP with RT (85% of whom also received chemotherapy), and160 patients (73%) received TL-PORT, 80% of patients in LP group had SIP and 20% had MIP. In comparison, 62% of TL-PORT patients had SIP while 38% had MIP. The 5-year LC was significantly better in LP patients with SIP compared to MIP (88% vs. 0%, P<.0001). However, the 5-year LC was not statistically different in patients with SIP compared to MIP in TL-PORT group (86% vs. 97%, P = 0.4). On multivariate analysis, MIP in LP cohort was the only independent predictor of LC (HR 19.4; 95% CI 5.5-80.3, P<.0001) but in TL-PORT group none of the studied variables (age, sex, ethnicity, larynx subsite of origin, performance status, nodal stage, radiation dose, chemotherapy use) was predictive of LC. LC for T4a laryngeal cancer patients with SIP and MIP is favorable in TL-PORT group, while LP should be eschewed for even minimal multi-anatomic site involvement but remains an option for selected cases with SIP.

Abstract 3472: Does being married independently predict survival in patients with head and neck cancer? Results from a single institution

Abstract Purpose/Objectives An important factor in cancer survivorship is social support, often coming from a spouse. There is an emerging literature on the role of spousal support in head and neck cancer (HNC) outcomes; however most are based on results from national databases. While more generalizable, these studies may not always capture the unique variation in different patient populations. This single institution study aimed to describe the association between marital status and outcomes of HNC; and to determine if marital status independently predicts survival in a local patient population. Materials/Methods We identified 460 patients aged 20 to 91 (59.31 ± 11.42) years diagnosed with squamous cell carcinoma of the head and neck at an academic tertiary referral center between 1997 and 2012 in this retrospective cohort study. Cox proportional hazards model assessed the effect of marital status on survival. Results are based on the final model constructed after accounting for covariates in the data. Results Our study population was made up of 73% males, and 82.2% Whites. We found an association between marital status and HNC survival. Unmarried HNC patients had a 66% increase in the hazard of death compared to married HNC patients (HR = 1.66, 95% CI = 1.23 - 2.23). This was after controlling for covariates, which included sociodemographic variables (age, race, sex, and health insurance status), social habits (tobacco and alcohol), primary anatomical subsite (oral cavity, oropharyngeal, laryngeal, and others), stage at presentation (early vs. late stage), and treatment modality (surgery, surgery with adjuvant therapies, other single modality therapy, and palliative care). Other factors found to be associated with an increased hazard of death were age (≥ 50 years), current tobacco use, late stage of presentation, palliative care, and laryngeal subsite. Conclusion Marital status is associated with head and neck cancer outcomes, and being married is an independent predictor of survival among patients. This result, found in previous national studies, held true in our local patient population. This underscores the need for the multidisciplinary HNC team to recognize this aspect of survivorship and to emphasize the need for social support among unmarried HNC patients. It could be that it is necessary to add social support to the clinical practical guidelines for managing head and neck cancer beyond palliative care. Citation Format: Nosayaba Osazuwa-Peters, Kara M. Christopher, Sean T. Massa, Lauren Cass, Ronald J. Walker, Mark A. Varvares. Does being married independently predict survival in patients with head and neck cancer? Results from a single institution. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3472.

Induction Chemotherapy Followed By Concurrent Chemoradiotherapy Versus Radiotherapy Alone In Locally Advanced HNSCC – An Experience From Medical College In West Bengal, India

&lt;p&gt;&lt;strong&gt;Introduction:&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;Locally advanced Head and neck cancers (LAHNSCCs) are emerging as an important public health issue in India. Our study was designed to provide NACT to LAHNSCC patients followed by comparison between chemoradiation versus only radiation in rural medical college.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Material and Method: &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;Histopathologically proven non-metastatic LAHNSCC were randomized into 2 arms. Patients in both arms initially received 3 cycles of NACT (inj Paclitaxel 175mg/m2 and inj Carboplation AUC 6, i.v, q 21 days). Thereafter they received definitive treatment accordingly: arm A (control arm) received conventionally fractionated radiotherapy (CFRT), 70 Gy in 35 # and in arm B (study arm) received conventionally fractionated radiotherapy (CFRT), 70 Gy in 35 # with concomitant 3 weekly cisplatin 100mg/m2. A RECIST v1.0 criterion was used for response assessment and toxicities evaluated by RTOG Acute and late Morbidity scorings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;Between July 2013 to December 2015, 140 patients were randomized into arms. Laryngeal and hypopharyngeal subsites together accounted for 36.4% patients. 70% of patients were in AJCC TNM 7th edition stage IV. 87.8% of patients completed the planned 3 cycles of NACT. Response assessment using RECIST v1.0 criteria after NACT were comparable in both arms with CR in 25% patients and PR in another 60% patients, p value 0.963. After completion of full treatment, 68.57% (48/70) patients in concurrent arm had CR against 55.72% patients (39/70) in only radiation arm, p value 0.241. At the end of study, 38 patients in arm A and 46 patients in arm B were eligible for response assessment. 24 patients (63.2%) in arm A were in complete response against 32 patients (69.6%) in concurrent chemoradiation arm, p value 0.535. Gastrointestinal and mucositis grade 3 toxicities were significantly increased in concomitant chemoradiation arm.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;Our study failed to show any statistical significant improvement in CR in favour of CTRT arm in our subset of patients. Yet definitive conclusion regarding use of only radiation cannot be made for LAHNSCC especially when combined with induction chemotherapy.&lt;/p&gt;

Head and Neck Tuberculosis: Scenario in a Tertiary Care Hospital of North Eastern India.

Tuberculosis has affected mankind since time immemorial and with emergence of AIDS both extrapulmonary and pulmonary tuberculosis presents increased morbidity and mortality along with an increased financial burden upon the developing nations. The study is a hospital based observational study of one year duration carried out in the Department of ENT in a tertiary care hospital of North Eastern India. Total of 63 cases were detected. Females comprised 60.3% of the study population as against 39.7% males. Most commonly affected age group were of 15 to 24 years age (57.1%). Cervical tubercular lymphadenitis was the most common lesion 90.5% (57 cases) followed by laryngeal tuberculosis 7.9% (5 cases) and tubercular otitis media with mastoiditis 1.6% (1 case). Level II lymph node was mostly affected either single or in groups (75.4%) followed by level III node (57.9%). Successful outcome of the treatment with Category I regimen was achieved in 96.8% of the cases. Head and neck tuberculosis is not an uncommon disease and though cervical lymphadenitis is the most common presentation, isolated involvement of the larynx, ear and other subsites are not an entirely unknown entity. The clinical presentation of tuberculosis of the head and neck region can be varied and often misleading. It is therefore important for the clinician to be aware of the condition and consider it in their differential diagnosis.

Abstract 1481: miR-296 as prognostic and predictive molecular marker for recurrence in early-stage laryngeal carcinoma treated with definitive radiotherapy

Abstract Early-stage laryngeal cancer has cure rates above 80% with exclusive radiotherapy. However, when salvage treatment is needed, surgery is the main option and despite efforts to conservative procedures to preserve laryngeal function, up to 50% will require total laryngectomy at diagnosis of recurrence or future. So, the use of microRNAs as molecular markers is a method to be tested with the aim of predicting the chances of success with radiotherapy, lowering tumor relapses and turning possible to reduce the need for salvage procedures that would affect speech and impact in quality of life. Objectives: To identify microRNAs capable of segregating radioresistant from radiosensitive tumors, to determine prognosis in pre-treatment tumors and to predict failure with radiotherapy. Methods: Molecular Screening of 667 microRNAs using taqman low density array (TLDA) for target selection and then validation in 34 patients, being 20 radioresistant and 14 radiosensitive by RT-PCR with individual assays. Statistical analysis was performed by Chi-square and Fisher exact test for associations between variables, and log-rank method of Kaplan-Meier for recurrence free survival between molecular, clinical, demographic and treatment variables. Also to verify differences in distribution between the expression levels in radioresistant and radiosensitive the Mann-Whitney test was performed. Results: Four microRNAs were selected for validation, miR-296, miR-452, miR-183*, miR-200c based on fold-change and literature review and those were analyzed with respect to age, gender, TNM, laryngeal subsite, radiation dose and treatment interval. Among clinical, demographic, treatment and molecular variables, only miR-296 was shown to present different distribution with statistical significance between radioresistant and radiosensitive (p = 0.002), also demonstrated association with recurrence (p = 0.01) with an odds ratio (OR) of 8.6, confidence interval (CI) between 1.7 and 42.2. Conclusions: In our study, only miR-296 demonstrated the ability to predict patients most likely to fail radiotherapy, also showing a worse prognosis for tumors with high expression level. miR-296 is a molecular predictive and prognostic marker to be considered prior to treatment selection for early-stage laryngeal tumors. Citation Format: Danielle C C Maia, Ana Carolina de Carvalho, Maria Aderuza Horst, Cristovam Scapulatempo Neto, Andre Lopes Carvalho, Andre L. Vettore. miR-296 as prognostic and predictive molecular marker for recurrence in early-stage laryngeal carcinoma treated with definitive radiotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1481. doi:10.1158/1538-7445.AM2014-1481

The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma.

The aim of this study was to determine the prognostic value of Ki-67 immunostaining in patients affected by laryngeal squamous cell carcinoma. A systematic review was carried out in a tertiary university referral center. An appropriate string was run on PubMed to retrieve articles dealing with Ki-67 immunohistochemical staining and laryngeal squamous cell carcinoma. A double cross-check was performed on citations and full-text articles by two investigators independently to review all manuscripts and perform a comprehensive quality assessment. Of 85 abstracts identified, 18 articles were included. These studies reported on 1,342 patients with histological confirmed diagnosis of laryngeal squamous cell carcinoma. Most studies showed a statistical association between Ki-67 immunohistochemical expression and at least one of the clinical and histopathological parameters considered by the authors. Overall the studies analyzed suggested that the tumoral proliferative index was statistically connected respectively with T stage (2/18), N stage (4/18), grading (6/18), disease-free survival (10/18) and overall survival (4/18). Our review strongly suggests that immunohistochemical staining of Ki-67 correlates with tumoral aggressiveness and worse prognosis in patients affected by laryngeal squamous cell carcinoma. Further high-quality prospective studies should be carried out to confirm our finding and determine the eventual differences between cancers of specific laryngeal subsites.

Occult nodal disease in patients with failed laryngeal preservation undergoing surgical salvage

The primary objective was to determine the incidence of pathologically positive lymph nodes in clinically N0 larynx cancer patients undergoing salvage surgery following nonsurgical primary therapy. Secondary aims included assessment of the impact of laryngeal subsite and neck dissection on disease status and survival. Retrospective chart review. Sixty-eight patients with recurrent laryngeal cancer and no evidence of neck disease who underwent salvage laryngectomy and neck dissection after undergoing failed primary radiotherapy or chemoradiation were examined. Main outcome measures included: standard demographics, primary, clinical, radiologic, and pathologic recurrent TNM stage, laryngeal subsite, nodal neck level, surgical intervention, margin status, disease status, survival, and imaging results. Fifty-three men and 15 women, aged 33 to 88 years (mean=62.7 years) with recurrent laryngeal cancer were included. Overall, 28.3% of patients had pathologic nodal disease, with supraglottic cancer showing the highest rate (60%, P=.02). Survival was not associated with laryngectomy type (P=.35). However, on multivariate analysis, laryngeal subsite was significantly predictive of survival with transglottic recurrences demonstrating decreased mean survival (20.7 months, P=.02), and supraglottic recurrences demonstrating prolonged mean survival (37.1 months, P=.03). Metabolic imaging (negative predictive value=0.86) proved more reliable than anatomic imaging (negative predictive value=0.71). The incidence of pathologically positive lymph nodes in clinically negative patients with recurrent laryngeal carcinoma following nonsurgical therapy warrants standard selective neck dissection. Subsite of recurrence, specifically supraglottis and transglottis, correlates with pathologic neck node positivity and survival. Metabolic imaging proved more reliable than anatomic imaging in negative predictability for nodal disease. 4.

What patients consider important: Temporal variations by early and late stage oral, oropharyngeal and laryngeal subsites

Functional outcomes are of high priority to cancer patients and are relevant when considering treatment strategies. This study aimed to collate and analyse importance rankings of UW-QOL over time for patients treated with curative intent for primary head and neck squamous cell carcinoma between 2000 and 2010, and to compare early and late stage oral, oropharyngeal and laryngeal subsites. There were 1614 patients comprising oral cavity 47% (751), oropharyngeal 24% (382), laryngeal 20% (320) and other HNC locations 10% (161). Items of importance remained relatively stable within clinical groups but there were notable differences between groups. For patients with early oral tumours no domain was especially dominant, whereas for late oral tumours swallowing, chewing, speech and saliva were selected more often. Swallowing and saliva were more important in oropharyngeal tumours, as was taste with more advanced oropharyngeal tumours. Speech and activity were important for those with early laryngeal tumours, as were swallowing and speech for more advanced laryngeal tumours. Swallowing and saliva were more important in advanced tumours for all sites. This data confirms the priority patients place on swallowing, chewing, speech, and saliva, therefore curative treatments should optimise these functions wherever possible and provide access to post-treatment interventions as required.

OP070: Emergent trends of perceived needs and concerns in long-term survivors of head and neck cancer using the patients concerns inventory

Objectives The Patients Concerns Inventory (PCI) is a holistic needs assessment tool to help patients disclose items of concern during routine clinical consultations. The University of Washington Quality of Life (UWQOL) is a validated, HNC-specific HRQOL, which can also screen for patients with significant problems. This study explored associations between PCI outcomes with UWQOL scores. Methods A cross-sectional study of 674 HNC patients (mean age 64 years; 67% men) who completed the HNC-PCI and UWQOL was undertaken. Relationships between HNC-PCI domain selection, UWQOL scores and patient/clinical characteristics were investigated, with statistical significance obtained as appropriate. Results Most (70%, 472) completed HNC-PCI only once (median, 39 months), while 30% (202) completed more than once. On first completing the HNC-PCI (median, 32 months from surgery/diagnosis), items under Physical and functional and Psychological and Emotional well-being/Spiritual domains were selected in 81% and 58%, respectively. When completing a second HNC-PCI, relatively fewer items per domain. Younger patients and those treated by radiotherapy were more likely to select from Psychological and Emotional well-being/Spiritual and Social care/Social well-being domains. Those treated by adjuvant radiotherapy and the larynx subsite were more likely to select from Social care/Social well-being domain. Clear associations were found between four HNC-PCI domains selected with UWQOL subscale scores, and also with the single item UWQOL and overall QOL, where patients in worse condition were more likely to select items within each HNC-PCI domains. Conclusions Emerging trends suggest that certain clinical-pathological factors are associated with specific presentation of perceived needs/concerns. The association between perceived needs with HRQOL outcomes endorses the importance of meeting unmet needs in long-term HNC survivors even though there is a suggestion that the unmet needs may reduce with time.

Effects of conjugated linoleic acid and high oleic acid safflower oil in the treatment of children with HPV-induced laryngeal papillomatosis: a randomized, double-blinded and crossover preliminary study.

BackgroundSurgery is the mainstay therapy for HPV-induced laryngeal papillomatosis (LP) and adjuvant therapies are palliative at best. Research revealed that conjugated-linoleic acid (CLA) may improve the outcome of virally-induced diseases. The effects of Clarinol™ G-80 (CLA) and high oleic safflower oil (HOSF) on children with LP (concomitant with surgery) were evaluated.DesignA randomized, double-blinded, crossover and reference-oil controlled trial was conducted at a South African medical university. Study components included clinical, HPV type/load and lymphocyte/cytokine analyses, according to routine laboratory methods.ParticipantsOverall: ten children enrolled; eight completed the trial; five remained randomized; seven received CLA first; all treatments remained double-blinded.InterventionChildren (4 to 12 years) received 2.5 ml p/d CLA (8 weeks) and 2.5 ml p/d HOSF (8 weeks) with a washout period (6 weeks) in-between. The one-year trial included a post-treatment period (30 weeks) and afterwards was a one-year follow-up period.Main outcome measuresChanges in numbers of surgical procedures for improved disease outcome, total/anatomical scores (staging system) for papillomatosis prevention/viral inhibition, and lymphocyte/cytokine counts for immune responses between baselines and each treatment/end of trial were measured.FindingsAfter each treatment all the children were in remission (no surgical procedures); after the trial two had recurrence (surgical procedures in post-treatment period); after the follow-up period three had recurrence (several surgical procedures) and five recovered (four had no surgical procedures). Effects of CLA (and HOSF to a lesser extent) were restricted to mildly/moderately aggressive papillomatosis. Children with low total scores (seven/less) and reduced infections (three/less laryngeal sub-sites) recovered after the trial. No harmful effects were observed. The number of surgical procedures during the trial (n6/available records) was significantly lower [(p 0.03) (95% CI 1.1; 0)]. Changes in scores between baselines and CLA treatments (n8) were significantly lower: total scores [(p 0.02) (95% CI −30.00; 0.00)]; anatomical scores [(p 0.008) (95% CI −33.00: -2.00)]. Immune enhancement could not be demonstrated.ConclusionsThese preliminary case and group findings pave the way for further research on the therapeutic potential of adjuvant CLA in the treatment of HPV-induced LP.

Issues patients would like to discuss at their review consultation: variation by early and late stage oral, oropharyngeal and laryngeal subsites

The patient concerns inventory (PCI) was developed to help patients raise issues/concerns during routine follow-up and to indicate team members they want to see. This paper reports the use of the PCI across various H&N Cancer sub-sites (oral, oropharyngeal and laryngeal) and stages of disease (early and late) and describes the main concerns that patients want to discuss using a cross-sectional survey comprising the PCI with the University of Washington Quality of Life questionnaire. Patients treated for primary H&N squamous cell carcinoma, 1998-2009, were identified from the University Hospital Aintree H&N Cancer database. 447/775 (58 %) patients responded. Fear of recurrence concerns was common to all clinical groups (range 32-67 %). Speech issues were more common with laryngeal tumours, and saliva issues with oropharyngeal tumours (32 % early, 48 % late). Apart from early-stage laryngeal tumours, patients consistently reported issues concerning dental health/teeth and chewing. The median (IQR) number of concerns overall was 4 (2-7), with significant variation (p < 0.001) between clinical groups ranging from 2 (1-6) for early-stage oral to 6 (2-10) for late-stage oropharyngeal and 7 (5-9) late-stage laryngeal. The results indicated that PCI can be readily incorporated into managing HNC patients and supports a holistic multidisciplinary approach to clinic consultations. It accommodates difficult issues such as fear of recurrence and intimacy. Completion of the PCI by patients before consultation can highlight problems and concerns that doctors can target for discussion, thereby streamlining consultations, and ensuring that patient needs are better met, thus creating a more effective service.

Potential Pitfalls and Therapeutic Implications of Pretherapeutic Radiologic Staging in Glottic Cancers

Objectives: The aim of this study was to compare the radiologic findings with histological results of anatomically matched whole organ sections and to analyze the accuracy of pretherapeutic radiologic staging of glottic cancers. Methods: The histologic findings of surgical specimens of 30 patients who had undergone total or conservative partial laryngectomy for glottic cancers were matched and compared with the pretherapeutic radiologic findings using CT and MR imaging. The accuracy of pretherapeutic radiologic staging was assessed for specific subsites for staging of glottic cancers. Results: The overall accuracy of pretherapeutic staging with CT and MR imaging was 84.9%; 12.1% associated with false positive and 3% associated with false-negative assessments. For all subsites, the overall sensitivity was 88%, specificity 84%, positive predictive value 65%, and negative predictive value 95%. Subsites such as the anterior commissure, paraglottic space, and preepiglottic space showed lower specificity (42%, 65%, and 79% respectively) than the overall specificity. The radiologic evaluation for cartilage invasion showed the accuracy of 84.8% and yielded acceptable specificity (89%) and high negative predictive value (98%). Conclusion: Although pretherapeutic radiological examination is a very useful technique for the evaluation of tumor invasion into specific laryngeal subsites, the pretherapeutic radiologic staging can be challenging when distinguishing tumor from peritumoral inflammation.

Competing mortality in advanced head and neck cancer: A population-based study.

5578 Background: Competing (noncancer) mortality (CM) is a common event in head/neck cancer (HNC) that complicates the interpretation of treatment effects. Population-based models are needed to estimate the impact of CM on power of HNC clinical trials. Methods: We analyzed 22,729 patients diagnosed with advanced nonmetastatic HNC between 1993 and 2004 using SEER data. We identified factors associated with cancer-specific mortality (CSM) and CM using the Fine-Gray proportional hazards model with backward stepwise regression. Risk scores for CM were derived from coefficient estimates and values of covariates retained in the model. The model was validated using bootstrap and split sample techniques. Power estimates assumed exponential hazards, 500 patients accrued over 3 years, 2 years follow-up, hazard ratio (HR) for all-cause mortality (ACM) of 0.67, and primary endpoint (PE) evaluation at 5 years. The HR for competing risk power estimates (0.63) was calibrated such that power was equivalent in the low CM risk tertile for both competing risk (using CSM as the PE) and standard methods (using ACM as the PE). Results: Median follow-up for surviving patients was 59 months. The 5-year cumulative incidence of ACM, CSM, and CM were 57%, 45%, and 12%, respectively. Risk factors for increasing CM were male sex (subdistribution HR [SHR] 1.17; 95% CI, 1.08-1.27), black race (SHR 1.12; 95%, CI 1.02- 1.24), low socioeconomic status (SHR 1.07; 95% CI, .99-1.16), age (SHR 1.04; 95% CI, 1.04-1.04), unmarried (SHR 1.27; 95% CI 1.19-1.37), grade 1-2 tumor (SHR 1.08; 95% CI 1.01-1.17), larynx subsite (SHR 1.15; 95% CI 1.07-1.24), and nonsurgical treatment (SHR 1.18; 95% CI 1.10-1.26). The 5-year cumulative incidence of CM for patients at low, medium, and high risk was 9%, 11%, and 17%, respectively. The Table shows that power is overestimated with standard methods as the risk for CM increases. Conclusions: Multiple demographic and tumor characteristics affect CM risk in the population, suggesting that competing risk methods should be considered for power calculation in HNC clinical trials. CM risk group 5-year cumulative incidence Power Additional patientsrequired (%) ACM CM ACM Competing risks Low 57% 9% 80% 80% 0 Medium 53% 11% 77% 74% 34 (7%) High 62% 17% 84% 78% 74 (15%) No significant financial relationships to disclose.

Evaluation of the incidence and prognostic value of mutant epidermal growth factor receptor (EGFRvIII) protein expression in head and neck squamous cell carcinomas (HNSCC) using AQUA.

5538 Background: EGFR VIII represents a common form of mutant EGFR and has been described in several cancers, mainly glioblastoma. Data derived from cell line and xenograft models indicate that EGFRVIII expression is implicated in resistance to targeting wild-type EGFR in HNSCC. Two studies (Sok et al, Hama et al) have evaluated the incidence of EGFRVIII expression in HNSCC. Sok et al reported the presence of EGFRVIII in 42% of HNSCC using immunohistochemistry and reverse transcription polymerase chain reaction whereas Hama et al reported no EGFRVIII mutation in HNSCC by sequencing full-length EGFR. We sought to evaluate the incidence and prognostic significance of EGFRVIII in a cohort of HNSCC who had not received EGFR-targeted therapy. Methods: A tissue microarray composed of 102 specimens from primary HNSCC cases was constructed. Protein expression for EGFRVIII was analyzed using an immunofluorescence-based assay that provides an automated, quantitative analysis of expression within subcellular compartments (AQUA). Primary study endpoints were progression-free PFS) and overall survival (OS). Survival analysis was performed by Kaplan-Meier method with log-rank test for determining statistical significance. Results: Mean follow-up time for the cohort was 42 months. EGFRVIII mutation was detected in 48% of HNSCC and was commonly found in conjunction with wild-type EGFR. No association between EGFRVIII and gender, stage or histologic grade was observed. However, laryngeal carcinomas expressed higher levels of EGFRvIII compared to oral cavity and oropharyngeal carcinomas (mean AQUA score 42 vs. 13 and 14 respectively, p < 0.001). In univariate survival analysis there was no significant correlation between EGFRVIII expression and PFS (p = 0.561) or OS (p = 0.962). Multivariable analysis also failed to identify EGFRVIII as prognostic factor in HNSCC. Conclusions: We found that EGFRVIII is detected in 48% of HNSCC and is associated with larynx subsite. There is no correlation between EGFRVIII expression and outcome. These results need to be validated in larger HNSCC cohorts and to be correlated with EGFRVIII mRNA expression. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration HistoRx HistoRx

Endoscopic Airway Management of Laryngeal Sarcoidosis

To report the results of treating laryngeal sarcoidosis with intralesional steroids and minimally invasive laser surgery. Sarcoidosis is a rare multisystem inflammatory disorder of unknown cause. Laryngeal involvement is extremely rare, and its optimal management remains controversial. Retrospective medical chart review. Settings Tertiary care center/national referral airway reconstruction center. Ten consecutive patients treated for laryngeal sarcoidosis between 2004 and 2008. Demographic and clinical information including extralaryngeal manifestations obtained from patient records, laryngeal anatomic subsite manifestation of disease, intraoperative findings, and scores from the Medical Research Council (MRC) dyspnea outcome assessment instrument (which was administered preoperatively, at the first postoperative outpatient visit 4-6 weeks later, and at last follow-up). The patients included 9 women and 1 man, a total of 2.8% of the unit's adult surgical airway case mix (10 of 353). Mean (SD) age at presentation was 37 (17) years. All patients presented with dyspnea and dysphonia; 2 required emergency tracheostomy prior to treatment. Six patients presented with isolated laryngeal sarcoid. Supraglottis and arytenoids were affected in all patients. The median number of endoscopic treatments was 2 (range, 1-4). Significant improvement in MRC dyspnea grading was found postoperatively (P < .05), and patients with tracheostomy were successfully decannulated. The mean (SD) follow-up time was 24 (18) months. There were no adverse effects of surgery. Nine patients had a substantial dose reduction or discontinuation of their systemic corticosteroid therapy following endoscopic treatment. Minimally invasive endoscopic surgery with intralesional corticosteroid injection and laser reduction is an effective method of controlling laryngeal sarcoid. It improves symptoms immediately with minimal morbidity and, most importantly, reduces the need for systemic steroid administration in most patients. This study supports early recognition and endoscopic intervention in the management of laryngeal sarcoidosis.