Larynx Cavity Research Articles

The role of elective neck dissection in patients with adenoid cystic carcinoma of the head and neck.

To investigate the frequency and outcomes of elective neck dissection (END) for adenoid cystic carcinoma (ACC) of the head and neck. The National Cancer Database was queried for a cohort study of patients with ACC of the major salivary glands, nasal cavity/nasopharynx, hard/soft palate, tongue, floor of mouth, larynx, and oral cavity who underwent primary surgical resection from 2004 to 2014. Multivariable logistic regression was used to identify predictors of END and occult nodal metastasis. Overall survival (OS) was estimated using the Kaplan-Meier method and modeled with Cox proportional hazards regression. Among 2,807 patients with ACC treated surgically, 636 (22.7%) underwent END. Patients with ACC of the salivary glands and tongue most frequently underwent END; patients with hard/soft palate (odds ratio [OR] 0.06, P < 0.001) and nasal cavity/nasopharynx (OR 0.05, P < 0.001) ACC rarely underwent END compared to patients with major salivary gland cancer. Increasing tumor (T) stage (T4 vs. T1, OR 3.02, P < 0.001) was associated with END. Patients with advanced T3 to T4 ACC of the major salivary glands demonstrated extended OS associated with END (5-year OS 78.1% vs. 70.4%, P = 0.041) on Kaplan-Meier analysis and with END with adjuvant radiation therapy (hazard ratio 0.55, P = 0.027) using Cox proportional hazards regression. Elective neck dissection for T4 ACC of the salivary glands (21.3%) and tongue (25.5%) most consistently revealed occult nodal metastasis. Elective neck dissection for ACC of the major salivary glands or tongue is most likely to reveal occult nodal metastasis. Elective neck dissection is associated with extended OS for advanced-stage ACC of the major salivary glands. NA Laryngoscope, 129:2094-2104, 2019.

Dosimetric comparison of intensity-modulated radiation therapy for early-stage glottic cancers with and without the air cavity in the planning target volume

For early-stage glottic cancers, intensity-modulated radiation therapy (IMRT) has been shown to have comparable local control to 3D-conformal radiotherapy with the advantage of decreased dose to the carotid arteries. The planning target volume (PTV) for early glottic cancers typically includes the entire larynx, plus a 3 to 5 mm uniform margin. The air cavity within the larynx creates a challenge for the inverse optimization process as the software attempts to “build up” dose within the air. This unnecessary attempt at dose build-up in air can lead to hot spots within the rest of the PTV and surrounding soft tissue. We hypothesized that removal of the air from the PTV would decrease hot spots and allow for a more homogeneous plan while still maintaining adequate coverage of the PTV.We analyzed 20 consecutive patients with early-stage glottic cancer, T1-2N0, who received IMRT at our institution from April 2015 to December 2016. Each patient received 63 to 65.25 Gy in 2.25 Gy per fraction. Two plans were created for each case: one in which the PTV included the laryngeal air cavity and one in which the air cavity was subtracted from the PTV to create a new PTV-air structure. Dosimetric variables were collected for PTV-air structure from both IMRT plans, including V100%, D98% D2%, and D0.2%. Dosimetric variables for spinal cord and the carotid arteries were also recorded. Homogeneity index (HI) defined as D98/D2 was calculated. Two-sided t-tests were used to compare dosimetric variables.The median PTV volume was 69.9 cc (standard deviation [SD] ± 28.7 cc) and the median air cavity volume removed was 11.0 cc (SD ± 3.4 cc). A 2-sided t-test revealed a statistically significant decrease in max dose (112.7% vs 108.8%, p value = 0.0002) and improvement of HI (0.93 vs 0.91, p value = 0.0023) for the PTV air in the IMRT plan optimized for PTV air, which had air excluded, compared to the IMRT plan optimized for PTV with air included. There was no significant worsening of PTV-air coverage or significant increase in doses to the organs at risk (OARs).The removal of the air cavity from the PTV for early-stage glottic cancers does not compromise PTV coverage or sparing of OARs and can result in a more homogeneous IMRT plan. A more homogeneous plan has the potential to reduce treatment morbidity, although further study is warranted to investigate the clinical impact of air cavity removal from the PTV.

Sarcomatoid carcinoma of the pyriform sinus: A rare malignancy in a rare location responsive to combination of chemotherapy and radiotherapy

Sarcomatoid carcinoma (SaC) is a rare variant of squamous cell carcinoma with sarcomatoid features having biphasic characteristic malignant mesenchymal spindle cell and squamous cell component comprising of dysplasia, carcinoma in situ, or invasive carcinoma. Most information about this malignant entity in the head-and-neck region has emerged from larynx and oral cavity with an incidence of 0.5%–3% and 1%, respectively, with very few cases reported in hypopharynx. We hereby report such a case in a 76-year-old male who presented with dysphagia and swelling right side neck. Clinicopathological evaluation showed a localized SaC hypopharynx. In view of old age and comorbidities of hypertension and diabetes, no surgical intervention was contemplated, and he was treated with definitive concurrent chemo-radiotherapy (CCRT). A thorough review of the literature revealed that while earlier reported cases underwent upfront surgery followed by adjuvant RT or adjuvant CCRT, we treated this case with combination of chemotherapy and RT resulting in a significant therapeutic effect.

Lymphotoxin‐β receptor‐NIK signaling induces alternative RELB/NF‐κB2 activation to promote metastatic gene expression and cell migration in head and neck cancer

Head and neck squamous cell carcinomas (HNSCC) preferentially spread to regional cervical tissues and lymph nodes. Here, we hypothesized that lymphotoxin-β (LTβ), receptor LTβR, and NF-κB-inducing kinase (NIK), promote the aberrant activation of alternative NF-κB2/RELB pathway and genes, that enhance migration and invasion of HNSCC. Genomic and expression alterations of the alternative NF-kB pathway were examined in 279 HNSCC tumors from The Cancer Genome Atlas (TCGA) and a panel of HNSCC lines. LTβR is amplified or overexpressed in HNSCC of the larynx or oral cavity, while LTβ, NIK, and RELB are overexpressed in cancers arising within lymphoid oropharyngeal and tonsillar sites. Similarly, subsets of HNSCC lines displayed overexpression of LTβR, NIK, and RELB proteins. Recombinant LTβ, and siRNA depletion of endogenous LTβR and NIK, modulated expression of LTβR, NIK, and nuclear translocation of NF-κB2(p52)/RELB as well as functional NF-κB promoter reporter activity. Treatment with a NIK inhibitor (1,3[2H,4H]-Iso-Quinoline Dione) reduced the protein expression of NIK and NF-κB2(p52)/RELB, and blocked LTβ induced nuclear translocation of RELB. NIK and RELB siRNA knockdown or NIK inhibitor slowed HNSCC migration or invation in vitro. LTβ-induces expression of migration and metastasis related genes, including hepatocyte growth/scatter factor receptor MET. Knockdown of NIK or MET similarly inhibited the migration of HNSCC cell lines. This may help explain why HNSCC preferentially migrate to local lymph nodes, where LTβ is expressed. Our findings show that LTβ/LTβR promotes activation of the alternative NIK-NF-κB2/RELB pathway to enhance MET-mediated cell migration in HNSCC, which could be potential therapeutic targets in HNSCC.

Morphology of GNAT3-immunoreactive chemosensory cells in the rat larynx.

The upper airways play important roles in respiratory defensive reflexes. Although solitary chemosensory cells and chemosensory cell clusters have been reported in the laryngeal mucosa of mammalian species, the distribution and cellular morphology of chemosensory cells remain unclear. In the present study, the distribution and morphology of solitary chemosensory cells and chemosensory cell clusters were examined by immunofluorescence for GNAT3 on whole-mount preparations of the rat laryngeal mucosa. Electrophysiological experiments were performed to analyze the respiratory reflexes evoked by bitter stimuli to the laryngeal cavity. In the whole area of the laryngeal mucosa, the numbers of GNAT3-immunoreactive solitary chemosensory cells and chemosensory clusters were 421.0±20.3 and 62.7±6.9, respectively. GNAT3-immunoreactive solitary chemosensory cells were mainly distributed in the mucosa overlying epiglottic and arytenoid cartilage, and chemosensory clusters were mainly distributed on the edge of the epiglottis and aryepiglottic fold. GNAT3-immunoreactive solitary chemosensory cells were slender with elongated processes or had a flask-like/columnar shape. The number of GNAT3-immunoreactive cells in chemosensory clusters was 6.1±0.4, ranging between 2 and 14 cells. GNAT3-immunoreactive cells in the cluster were variform and the tips of apical processes gathered at one point at the surface of the epithelium. The tips of apical cytoplasmic processes in solitary chemosensory cells and cells in the cluster were immunoreactive for espin, and faced the laryngeal cavity. Physiological experiments showed that the application of 10mm quinine hydrochloride to the laryngeal cavity decreased respiratory frequency. The present results revealed the chemosensory field of the larynx and the morphological characteristics of the laryngeal chemosensory system for respiratory depression.

Salivary MicroRNAs for Early Detection of Head and Neck Squamous Cell Carcinoma: A Case-Control Study in the High Altitude Mestizo Ecuadorian Population.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with the highest incidence worldwide. HNSCC is often diagnosed at advanced stages, incurring significant high mortality and morbidity. The use of saliva, as a noninvasive tool for the diagnosis of cancer, has recently increased. Salivary microRNAs (miRNAs) have emerged as a promising molecular tool for early diagnosis of HNSCC. The aim was to identify the differential expression of salivary miRNAs associated with HNSCC in the high altitude mestizo Ecuadorian population. Using PCR Arrays, miR-122-5p, miR-92a-3p, miR-124-3p, miR-205-5p, and miR-146a-5p were found as the most representative ones. Subsequently, miRNAs expression was confirmed in saliva samples from 108 cases and 108 controls. miR-122-5p, miR-92a-3p, miR-124-3p, and miR-146a-5p showed significant statistical difference between cases and controls with areas under the curve (AUC) of 0.73 (p < 0.001), 0.70 (p < 0.001), 0.71 (p = 0.002), and 0.66 (p = 0.008), respectively. miRNAs were also deregulated in between HNSCC localizations. A differentiated expression of miR-122-5p between oral cancer and oropharynx cancer (AUC of 0.96 p = 0.01) was found: miR-124-3p between larynx and pharynx (AUC = 0.97, p < 0.01) and miR-146a-5p between larynx, oropharynx, and oral cavity (AUC = 0.96, p = 0.01). Moreover, miR-122-5p, miR-124-3p, miR-205-5p, and miR-146a-5p could differentiate between HPV+ and HPV- (p=0.004). Finally, the expression profiles of the five miRNAs were evaluated to discriminate HNSCC patient's tumor stages (TNM 2-4). miR-122-5p differentiates TNM 2 and 3 (p = 0.002, AUC = 0.92), miR-124-3p TNM 2, 3, and 4 (p < 0.001, AUC = 98), miR-146a-5p TNM 2 and 3 (p < 0.001, AUC = 0.97), and miR-92a-3p TNM 3 (p < 0.001, AUC = 0.99). Taken together, these findings show that altered expression of miRNAs could be used as biomarkers for HNSCC diagnosis in the high altitude mestizo Ecuadorian population.

Squamous cell carcinoma of the head and neck in children

ObjectiveTo discuss the presentation, evaluation, and management of squamous cell carcinoma of the head and neck in the pediatric population. MethodsMedical records of pediatric (≤20 years) patients treated for squamous cell carcinoma of the head and neck between 1996 and 2016 were reviewed. Data pertaining to clinical presentation, diagnostic methods, treatment plan, complications, recurrence, follow-up, or outcome were collected. ResultsEleven patients were diagnosed with squamous cell carcinoma. Seven of these patients had medical histories significant for prior malignancies, immunosuppressant therapy, and/or genetic syndromes. Lesions were identified in the oral cavity (n = 5, 45.5%), lip/upper lip (n = 3, 27.3%), larynx (n = 2, 18.2%), and nasal cavity (n = 1, 9.1%). Tumors were most commonly treated with surgical excision alone. Three patients underwent irradiation (2 adjuvant and 1 without surgery) and chemotherapy (1 adjuvant, 1 neoadjuvant, and 1 without surgery). Of these patients, one reported complications of hearing loss, loss of dentition, and laryngeal stenosis. Two patients developed local recurrence at 1 month and 5 years post-operatively, respectively. One patient developed an orocutaneous fistula and subsequently died. No other complications were reported. Median follow-up time was 4.6 years (interquartile range: 2.4–8.4 years). Complications of radiation included: laryngeal stenosis, wound breakdown, and orocutaneous fistula. ConclusionSquamous cell carcinoma is rare in the pediatric population. Most frequently, it is associated with previous malignancies, immunosuppressant therapy, and/or genetic conditions. Complete surgical excision is recommended to obviate the need for radiation whenever possible.

Survival in sinonasal and middle ear malignancies: a population-based study using the SEER 1973\u20132015 database

BackgroundThe sinuses, nasal cavity, and middle ear represent a rarer location of head and neck malignancy than more common sites such as the larynx and oral cavity. Population-based studies are a useful tool to study the demographic and treatment factors affecting survival in these malignancies.MethodsPopulation-based database search of the Survival, Epidemiology, and End Results (SEER) database from 1973 to 2015 for malignancies involving the nasal cavity, paranasal sinuses, and middle ear. Data were analyzed for demographics, treatment type, stage, primary site and histopathologic type. Kaplan-Meier analysis was used to assess and compare survival.ResultsA total of 13,992 cases of sinonasal or middle ear malignancy were identified and analyzed. The majority of patients were between ages 50 and 80 at the time of diagnosis. Overall 5-, 10-, and 20-year survival was 45.7%, 32.2%, and 16.4%, respectively. Lymph node metastasis was reported in 4.4% of patients, while distant metastasis was present in 1.5% of cases. On univariate analysis surgical vs. nonsurgical treatment, sex, race, age at diagnosis, T stage, N stage, M stage, AJCC overall stage, primary site, tumor grade, and histopathologic subtype significantly affected survival. On multivariate analysis age, race, sex, primary site, overall AJCC stage, surgical vs. nonsurgical treatment, and T, N, and M stage remained significant predictors of overall survival.ConclusionsMalignancies of the nasal cavity, paranasal sinuses, and middle ear account for a minority of overall head and neck cancers. The overall 5-, 10-, and 20-year survival for these malignancies is relatively low. Higher T, N, M, and overall stage and higher tumor grade is associated with lower survival. Patients treated with surgery as part of the treatment regimen had higher overall survival. Demographics and primary site also significantly affect survival. Certain histopathologic subtypes were associated with poorer survival.

Types of tobacco and alcoholic beverages use and head and neck cancer: A case-control study in state of São Paulo, Brazil, 1999–2015

Introduction Risk factors for health problems change over time and space. With regard to head and neck cancer (HNC), associations with smoking and alcohol consumption are well-established. Literature data suggest that the most prevalent types of tobacco and alcohol in a population are associated with higher risks of cancer. In Brazil, few epidemiological studies have investigated the effect of different types of tobacco and alcohol on HNC. The aim of this study was to measure the probabilistic risks for HNC by tobacco and alcohol types in non-exclusive consumption (use of more than one type of tobacco or alcoholic beverage) and exclusive consumption (use of only one type of tobacco or alcoholic beverage). Types of tobacco analysed were industrialized cigarette, hand-rolled cigarettes, pipe and cigar. The analyzed alcoholic beverages were distilled, beer and wine. Methods The present study has origin from three multicentric projects: Latin American, conducted from 03/1999 to 12/2001; Clinical Genome of Cancer performed from 07/2000 to 08/2011; and the Thematic Markers of Aggression in Head and Neck Tumors (GENCAPO), conducted from 07/2011 to 06/2015. Thus, it is a case-control study with data from hospitals in the State of Sao Paulo. The cases were diagnosed with squamous cell carcinoma of the head and neck, histologically confirmed. The controls, patients with diseases other than cancer, were selected in some of the hospitals where the cases originated. Both cases and controls were interviewed through questionnaires with information on characteristics and habits, as well as data on education and occupational history. Associations between the variables tobacco type and type of alcoholic beverages with HNC were estimated by the odds ratio (OR) and respective 95% confidence interval (95% CI) through non-conditional logistic regression adjusted for confounding variables: sex (female, male), age ( 100 and ≤ 900 and > 900 kg, to adjust the effect of tobacco). Results The risks due to smoking were more significant for the hypopharynx, particularly, in the non-exclusive pattern and consumption ≥ 40 packs per year OR: 36.1 (95% CI: 11.1–117.6); for oropharynx, larynx and oral cavity, the risks were: OR: 16.1 (95% CI: 10.4–24.9); OR: 14.2 (95% CI: 9.6–21.0); OR: 7.4 (95% CI: 5.6–10.0). In the exclusive consumption condition, for the same category ≥ 40 packets per year for industrialized cigarettes, the risks were slightly less intense: OR: 31.9 (95% CI: 9.7–104.3); OR: 15.4 (95% CI: 9.9–24.0); OR: 13.1 (95% CI: 8.8–19.5); OR: 7.1 (95% CI: 5.3–9.6), respectively, for hypopharynx, oropharynx, larynx and oral cavity. In alcohol consumption, higher associations of HNC with distilled beverages were observed. In the exclusive consumption condition, consumption level of distilled ≥ 2000 kg induced OR: 39.1 (95% CI: 12.7–121.8) for oropharynx. Simultaneous use of tobacco and alcohol increased the risk of HNC: OR: 10.5 (95% CI: 8.5–13.0). Conclusions Among smokers with the non-exclusive pattern of consumption, the greatest risks were observed for the hypopharynx. Among the consumers of alcoholic beverages, the distilled conferred greater risks in the two patterns of consumption. In beer and wine consumption, differences in intensity of associations with HNC became evident only in the higher consumption categories.

Abstract 1195: Incidence rates of head and neck cancer across Thailand and the USA

Abstract Background: Head and neck cancer is the sixth most common cancer in the world, with the largest burden occurring in developing countries. Although the primary risk factors have been well characterized, little is known about the temporal trends in head and neck cancer across Thailand. Using population based registries from three Thai provinces (Songkhla, Lampang and Khon Kaen), we have characterized the age-standardized incidence rates of head and neck cancer by sex and age and compared them to those observed in the United States. Methods: Cancer cases diagnosed between 1990 and 2014 were selected by ICD-10 code directly from the Songkhla, Lampang and Khon Kaen Cancer Registries as well as the Surveillance, Epidemiology, and End Results Program (SEER) for the following sites: oral cavity (00, 03-06), tongue (01-02), pharynx (09-10, 12-14), and larynx (32). The data were analyzed using R software (3.1.1) and Joinpoint Regression Software (4.4.0) to determine age-standardized incidence rates and trends of annual percent change. Incidence rates were standardized using the Segi (1960). Additional exploratory analyses using stratified linear regression models were conducted to assess temporal trends in head and neck cancer across 10-year age groupings. Results: Overall head and neck cancer rates are decreasing across all registries except Khon Kaen, where there is an observed, albeit not statistically significant, increase among males (APC: 0.53, p=0.3). Subsite analyses demonstrate consistent decreases in both larynx and oral cavity cancers, but suggested increases in pharynx and tongue cancers among both genders in the US (APC: 1.9 and 1.6, p&amp;lt;0.05 respectively) as well as pharynx cancer in Khon Kaen males (APC: 2.1, p&amp;lt;0.05). Furthermore, age-stratified APC analyses showed increased incidence in tongue cancer among Khon Kaen females age 30-39, Khon Kaen males age 30-59, Lampang males age 50-59, Songkhla females age 30-49, US females age 30-49 and 70-85+, as well as US males age 40-79. Pharynx cancers were seen to increase in Khon Kaen males age 40-59 and US males age 50-59. Conclusions: Although overall trends in head and neck cancer do seem to be decreasing across both Thailand and the United States, there is reason to believe that the etiological shift affecting both pharynx and tongue cancers in the US may be similarly presenting in Thailand. While disparities across gender and region do still exist, further investigation into the increased rates of early onset cancer is needed. Citation Format: Ilona Argirion, Katie Rentschler, Patravoot Vatanasapt, Hutcha Sriplung, Laura S. Rozek. Incidence rates of head and neck cancer across Thailand and the USA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1195.

Prognostic Role of p16 in Nonoropharyngeal Head and Neck Cancer.

Previous studies have reported conflicting information regarding the prognostic role of p16 in nonoropharyngeal head and neck squamous cell carcinoma (HNSCC). Using the US Veterans Affairs database, we analyzed 1448 patients with locoregionally advanced HNSCC and known p16 status diagnosed between 2005 and 2015 and treated with surgery, radiotherapy, or chemoradiotherapy. Tumor p16 status was determined through manual review of pathology reports of primary tumor specimens. Oropharyngeal (n = 1061) or nonoropharyngeal (n = 387; hypopharyngeal, laryngeal, or oral cavity) tumor site was determined from tumor registry data and manually reviewed for accuracy. We used multivariable Cox regression to analyze the effect of p16 status on overall survival (OS), cancer-specific survival (CSS), and competing mortality (CM) for oropharyngeal or nonoropharyngeal tumor sites. All statistical tests were two-sided. In multivariable models adjusting for treatment, stage, age, comorbidity, and body mass index, patients with p16-positive tumors had improved OS, CSS, and CM compared with patients with p16-negative tumors in both oropharyngeal (OS: hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.40 to 0.71, P < .001; CSS: HR = 0.50, 95% CI = 0.35 to 0.73, P < .001; CM: HR = 0.59, 95% CI = 0.38 to 0.93, P = .02) and nonoropharyngeal primary sites (OS: HR = 0.41, 95% CI = 0.25 to 0.69, P < .001; CSS: HR = 0.37, 95% CI = 0.18 to 0.77, P = .008; CM: HR = 0.46, 95% CI = 0.23 to 0.95, P = .04). The prognostic impact of p16 status did not statistically significantly differ by primary tumor site for OS, CSS, or CM (Pinteraction > .05). Our findings support the hypothesis that p16 has a similar prognostic role in both nonoropharyngeal and oropharyngeal cancer. Consideration should be given to increased testing for p16 in laryngeal, hypopharyngeal, and oral cavity primaries.

Discontinuation of Curative Head and Neck Irradiation: Etiologies and Outcomes

There is scarcity of valid clinical data on survival after premature discontinuation of curative radiation therapy (PDCRT) for head and neck (H&N) cancers. This makes it challenging to advise patients seeking to withdraw from treatment early. In this study, we aimed to characterize causes of PDCRT and assess overall survival in this subset of patients A total of 1176 patients received H&N radiation therapy at our institution in the period 2010-2017. Of these patients, 59 (5%) were unable to complete a full course of prescribed curative RT and were included in the analysis. Mean follow-up time was 18 months (0-81.9 months). Primary endpoints were causes of PDCRT and overall survival (OS). PDCRT causes were classified into five categories: discontinuation against medical advice (DAMA), medical comorbidity, RT toxicity, disease progression, and social factors. Survival was examined using the life-table method and log-rank test. DAMA (32%), medical comorbidity (24%), and RT toxicity (18%) accounted for the majority of PDCRT causes. Of 59 analyzed patients, most were men (80%), ≥60 years old (59%), white (68%), lived ≥ 10 miles from hospital (61%), were undergoing a longer (definitive) course of RT (59%), and receiving bilateral neck irradiation (70%). At the same time, the majority of patients had ECOG ≤1 (78%) and ≤1 comorbidities (56%) at the start of the treatment. Most common primary sites were oropharynx (37%), larynx (20%), and oral cavity (12%). During RT, 66% of patients had treatment interruptions and 34% required inpatient admission. Supportive Oncology service was involved in care of only 20% patients on treatment. Radiation Therapy Oncology Group grade ≥2 dysphagia was observed in 47% patients, mucositis in 46%. Median prescribed dose was 69.96 Gy (range, 50-72 Gy). Median completed radiation dose was 50.9 Gy (range, 2-68 Gy). At the time of analysis, 25 (42%) deaths were recorded. Two-year and 4-year OS rates was 56% and 43%. There was a trend toward improved survival with total completed dose ≥ 50 Gy vs < 50 Gy, 67% vs 40% (P=.06). To the best of our knowledge, this is the largest modern study examining clinical outcomes after PDCRT. The principal reason for treatment withdrawal remains DAMA, and hence more effort need to be focused on educating and providing support to meet the unique needs of this challenging patient population. Addressing psycho-social and quality of life aspects may help increase completion rates of this often life-saving treatment. Overall survival appears to be poor after PDCRT. Advising a patient that reaching at least 50 Gy could offer a better chance for survival could prove vital.

What Is the Benefit of Adjuvant Radiation Doses Above 60 Gy in Head and Neck Cancer Patients?

Radiation dose response data in the postoperative management of Head and Neck Squamous Cell Carcinoma (HNSCC) are limited. We compared radiation dose trends and outcomes of HNSCC treated with adjuvant radiation, with or without concurrent chemotherapy. Patients with non-metastatic HNSCC who were treated between 2004 and 2014 with primary site surgery, lymph node dissection, and adjuvant radiation with an equivalent dose in 2 Gy (EQD2) of ≥ 56.64 Gy (equivalent to 57.6 Gy in 32 fractions) and ≤ 72 Gy were identified in the National Cancer Database. Radiation doses of EQD2 < 56.64 Gy and > 72 Gy were respectively interpreted to reflect incomplete radiation courses or attempted salvage of gross recurrences prior to the initiation of radiation and were excluded. Standard dose radiation was defined as an EQD2 of ≥ 56.64 Gy and ≤ 60 Gy and high dose radiation as an EQD2 of > 60 Gy and ≤ 72 Gy. Radiation regimens employed in < 10 patients were excluded. We used multivariate logistic regression to model receipt of high dose radiation, and multivariate cox proportional hazards regression to assess the association between dose and survival within the cohorts of interest. We identified 19,492 patients managed with adjuvant radiation. Oral cavity, oropharynx, larynx, hypopharynx, and nasal cavity comprised 43%, 38%, 14%, 3%, and 2% of the primary sites, respectively. HPV status was available for 3496 (47%) oropharynx patients. High dose radiation was prescribed to 52% of patients. Factors that predicted for increased use of high dose radiation included extra-nodal extension (ENE), positive or unknown surgical margins, fewer examined lymph nodes, increased number of positive lymph nodes, increased N staging, concurrent chemotherapy, and non-tonsil primary site. When adjusted for known poor prognostic factors to control for high dose being prescribed to a worse prognosis cohort, there was a decrease in overall survival (OS) in the high dose group (HR = 1.10; 95% CI 1.03-1.17). High dose radiation was independently associated with worse OS in HPV positive oropharynx patients when controlling for poor prognostic factors (HR = 2.03; 95% CI 1.22-3.37). In non-oropharynx primary or HPV negative oropharynx primary that had positive margins, ≥ 5 positive lymph nodes, and/or ENE, high dose radiation was not associated with improvement in OS (HR 1.03; 95% CI 0.94-1.13). Factors known to predict for poor outcomes are associated with higher rates of high dose adjuvant radiation in this large national cohort. However, when controlling for poor prognostic factors, there was no survival benefit from postoperative dose escalation above EQD2 of 60 Gy.

Prognostic Role of p16 in Non-oropharyngeal Head and Neck Cancer

Previous studies have reported conflicting information regarding the prognostic role of p16 in non-oropharyngeal head and neck squamous cell carcinoma (HNSCC). We investigated the association between p16 status and cause-specific mortality in a large sample of United States veterans with oropharyngeal or non-oropharyngeal head and neck cancer (Table 1). Using the United States Veterans Affairs database, we analyzed 8727 patients with locoregionally advanced HNSCC diagnosed between 2005 and 2015 and treated with radiation therapy or chemoradiation therapy. Of these, 1538 had known p16 status, determined by review of clinical notes and pathology reports. We compared outcomes for 1164 patients with oropharyngeal HNSCC and 374 patients with non-oropharyngeal (oral cavity, hypopharyngeal, or laryngeal) HNSCC, using multivariable Cox proportional hazards regression models to test effects on overall survival (OS), cancer-specific survival (CSS), and competing mortality (CM) within strata. We also tested for significant interactions between p16 and non-oropharyngeal primary site for each outcome. In multivariable models adjusting for treatment, stage, age, comorbidity, and body mass index, patients with p16 positive tumors had improved OS, CSS, and CM compared to patients with p16 negative tumors in both oropharyngeal (OS: hazard ratio [HR] 0.57, P<.001; CSS: HR 0.54, P<.001; CM: HR 0.63, P = .04) and non-oropharyngeal primary sites (OS: HR 0.48, P<.001; CSS: HR 0.46, P = .007; CM: HR 0.49, P = .03). The prognostic impact of p16 status did not significantly differ by primary tumor site for OS, CSS, or CM (interaction P values all >.05). Our findings support the hypothesis that p16 has a similar prognostic role in both non-oropharyngeal and oropharyngeal cancer. Strong consideration should be given to routine testing for p16 in laryngeal, hypopharyngeal, and oral cavity primaries.Abstract 100; Table 1OutcomeModelOropharyngealNon-oropharyngealHazard ratio for p16+ (95% CI)P valueHazard ratio for p16+ (95% CI)P valueOverall survivalUnadjusted0.34 (0.26-0.43)<.0010.52 (0.34-0.79)<.001Adjusted0.61 (0.46-0.80)<.0010.47 (0.31-0.73)<.001Cancer-specific survivalUnadjusted0.28 (0.21-0.39)<.0010.52 (0.30-0.90).02Adjusted0.55 (0.38-0.78)<.0010.42 (0.23-0.74).003Competing MortalityUnadjusted0.43 (0.29-0.65)<.0010.52 (0.28-0.99).05Adjusted0.72 (0.46-1.13).150.53 (0.28-1.02).06 Open table in a new tab

The influence of smoking, age and stage at diagnosis on the survival after larynx, hypopharynx and oral cavity cancers in Europe: The ARCAGE study.

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.

Evaluation of Dynamic CT Scans and Analyzing Its Efficacy Accuracy in Staging of Laryngeal CA: A Prospective Analysis of 30 Patients and Review of Literature.

Laryngeal and hypopharyngeal cancer is the most common cancer in the head and neck. It is the most commonly reported human malignancy, with more than 100,000 cases reported annually worldwide. Thus, exact staging of the tumor is of utmost importance in the decision making of themanagement of these patients. CT can directly evaluate penetration of tumor into the laryngeal soft tissues and cartilages; whereas laryngoscopy and contrast laryngography can only infer deepseated abnormalities from changes in surface contour of the laryngeal cavity. The main aims of our study were: (1) To assess whether dynamic CT scans increase the diagnostic efficacy for laryngeal and hypopharyngeal cancers and its extent in surrounding structures. (2) To assess the importance of phonation CT scans in evaluation and diagnosis of vocal cord paralysis/fixity and involvement of subglottic region and pre epiglottic space.

Patterns of postoperative radiotherapy for head and neck cancer in Italy: a prospective, observational study by the head and neck group of the Italian Association for Radiation Oncology (AIRO)

Our previous survey showed that the patterns of postoperative radiotherapy (PORT) for head and neck cancer (HNC) in Italy might be suboptimal. A prospective observational study was therefore designed to evaluate this issue in greater detail. All radiotherapy centers involved in the HNC Working Group of the Italian Radiation Oncology Association were asked to enter into the study all patients treated with PORT during a 6-month period. A total of 200 patients were accrued by 24 centers from December 2008 to May 2009. Larynx (38%) and oral cavity (34%) were the most common primary sites. The median time between surgery and the start of radiotherapy was 69 days (range, 25-215 days). Seventy-nine percent of cases with no evidence of risk factors for local recurrence were treated with high-dose radiotherapy to the primary site. In about 75% of cases the pN0 neck was included in the target volume. Concomitant chemotherapy was delivered to about 60% of patients with major risk factors and 21% of patients with no risk factors. Three issues emerged from our study as potential targets for future investigations: the impact on clinical outcome of the interval between surgery and the start of PORT; factors driving radiation oncologists to overtreat volumes at low risk of recurrence; and problems associated with the delivery of concomitant chemotherapy.

Analysis of Site-Specific Methylation of Tumor-Related Genes in Head and Neck Cancer: Potential Utility as Biomarkers for Prognosis.

Clarifying the epigenetic regulation of tumor-related genes (TRGs) can provide insights into the mechanisms of tumorigenesis and the risk for disease recurrence in HPV-negative head and neck cancers, originating in the hypopharynx, larynx, and oral cavity. We analyzed the methylation status of the promoters of 30 TRGs in 178 HPV-negative head and neck cancer patients using a quantitative methylation-specific PCR. Promoter methylation was correlated with various clinical characteristics and patient survival. The mean number of methylated TRGs was 14.2 (range, 2–25). In the multivariate Cox proportional hazards analysis, the methylation of COL1A2 and VEGFR1 was associated with poor survival for hypopharyngeal cancer, with hazard ratios: 3.19; p = 0.009 and 3.07; p = 0.014, respectively. The methylation of p16 and COL1A2 were independent prognostic factors for poor survival in laryngeal cancer (hazard ratio: 4.55; p = 0.013 and 3.12; p = 0.035, respectively). In patients with oral cancer, the methylation of TAC1 and SSTR1 best correlated with poor survival (hazard ratio: 4.29; p = 0.005 and 5.38; p = 0.029, respectively). Our findings suggest that methylation status of TRGs could serve as important site-specific biomarkers for prediction of clinical outcomes in patients with HPV-negative head and neck cancer.

Robustness Evaluation of a Novel Proton Beam Geometry for Head and Neck Patients Treated with Pencil Beam Scanning Therapy

Background: To evaluate the robustness of head and neck treatment using proton pencil beam scanning (PBS) technique with respect to range uncertainty (RU) and setup errors (SE), and to establish a robust PBS planning strategy for future treatment. Methods and Materials: Ten consecutive patients were planned with a novel proton field geometry (combination of two posterior oblique fields and one anterior field with gradient dose match) using single-field uniform dose (SFUD) planning technique and the proton plans were dosimetrically compared to two coplanar arc VMAT plans. Robustness of the plans, with respect to range uncertainties (RU = ± 3% for proton) and setup errors (SE = 2.25 mm for proton and VMAT), in terms of deviations to target coverage (CTV D98%) and OAR doses (max/mean), were evaluated and compared for each patient under worst case scenarios. Results: Dosimetrically, PBS plans provided better sparing to larynx (p = 0.005), oral cavity (p -1.1% ± 1.3 % vs -0.4% ± 0.7% for nodal CTV and -1.4% ± 1.2 vs -0.4% ± 0.5% % for boost CTV). Overall, the magnitudes of variation of CTV D98% to combined SE and RU were found to be similar to the impact of the SE on the VMAT plans (-1.6% ± 1.9% vs -1.7% ± 1.4% for nodal CTV and -1.9% ± 1.6% vs -1.3% ± 1.5% for boost CTV). Compared to VMAT, a larger range of relative dose deviations were found for OARs in proton plans, but safe doses were maintained for cord (41.8 ± 3.6 Gy for PBS and 41.7 ± 3.9 Gy for VMAT) and brainstem (35.2 ± 8.4 Gy for PBS and 36.2 ± 5.1 Gy for VMAT) in worst case scenarios. Conclusions: Compared to VMAT, proton plans containing three SFUD fields with superior-inferior gradient dose matching had improved sparing to larynx, contralateral parotid and oral cavity, while providing similar robustness of target coverage. Evaluation of OAR dose robustness showed higher sensitivities to uncertainties for proton plans, but safe dose levels were maintained for cord and brainstem.

Comparative analysis of quality of life in advanced laryngeal and oral cancer undergoing extensive surgeries

Introduction: Total laryngectomy has significant impact in vital functions of patients as breath, swallow and speech, and may influence their quality of life. The COMMANDO surgery followed by adjuvant radiotherapy is a mutilating surgery that impacts patients swallowing, saliva, chewing, and speech, interfering with their quality of life. Objective: To describe and evaluate comparatively factors associated with lower quality of life in patients with advanced larynx and oral cavity cancer undergoing extensive surgeries. Materials and Methods: 95 patients with laryngeal cancer and 47 with oral cavity cancer underwent extensive surgeries. The fourth version of University of Washington Quality of Life Questionnaire (UW-QOL) was used. Results: Regarding the subjective domains, they evaluate quality of life related to health as good in both subsites. Worst scores in QOL domains after total laryngectomy were presented in mood, activity, rehabilitation through esophageal speech and absence of vocal emission. Worst scores in QOL domains after COMMANDO were presented in chewing, swallowing, speech, and absence of saliva. The average composite score for quality of life in larynx was 80.4 and oral cavity was 64.6. Conclusion: The high value for the average composite score of QOL after total laryngectomy showed positive assessment of QOL compared to lower values reported after COMMANDO. The absence of vocal emission was the only domain independently associated with a decreased QOL according to the UW-QOL. Oral cavity patients reported that they cannot even chew soft foods and can only eat some solid food.