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Introduction: The response to induction chemotherapy (IC) predicts local control after conservative treatment of laryngeal, meso- and hypopharyngeal head and neck squamous cell carcinoma (HNSCC) and can thus help to avoid surgery. Single-cycle induction chemotherapy may help to maintain a low local recurrence rate while keeping the overall toxicity manageable. However, long-term data on single-cycle IC response by tumor location is lacking., Methods: N = 102 patients with functionally inoperable primary HNSCC of the larynx (n = 43), hypopharynx (n = 42) or mesopharynx/tongue (n = 17) received one cycle of docetaxel (75 mg/m 2 , d1) plus cisplatin (30 mg/m 2 , d1-3) or carboplatin (AUC 1.5, d1-3) and a response evaluation 3 weeks later. Responders (≥ 30% tumor size reduction and ≥ 20% SUVmax decrease in 18 F-FDG PET/CT) were recommended chemoradiotherapy (CRT), and non-responders surgery., Results: The overall response rate was 72.5%. All 74 responders and 10 non-responders received primary CRT, and 18 patients received primary surgery after single-cycle IC. Overall 10-year local recurrence-free survival (LRFS) was 73.7%. Three-year LRFS was 88.2% (mesopharynx/tongue), 88.2% (larynx), and 73.3% (hypopharynx); p = 0.17. 3-year distant metastasis-free survival (DMFS) was 94.1% (mesopharynx/tongue), 88.0% (larynx) and 76.4% (hypopharynx); p > 0.05. This influenced the 3-year cancer-specific survival (CSS) for larynx (91.2%) vs. hypopharynx tumors (60.8%); p = 0.003, but CSS was not different to tumors in the mesopharynx/tongue (81.4%); p > 0.05., Conclusions: A single-cycle induction chemotherapy for HNSCC enables surgery plus adjuvant therapy as well as chemoradiotherapy. The long-term local and distant disease control was good but varied between tumors in the larynx and mesopharynx/tongue vs. hypopharynx.

Background: Adding concurrent chemotherapy (CTx) to definitive radiation therapy (RT) in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) improves overall survival. A comparable effect has been reported for hyperfractionated radiotherapy (HFX-RT) alone. Adding concurrent CTx to HFX-RT has been investigated in multiple trials, yet an evident effect on oncological outcomes and toxicity profile has not been established to date. Thus, the aim of the current study was to perform a meta-analysis on the clinical outcome and toxicity of the addition of CTx to HFX-RT., Patients and Methods: We performed a literature search for randomized controlled trials comparing HFX-RT alone to HFX-RT + concurrent CTx in patients with LA-HNSCC undergoing definite RT. A meta-analysis was performed using the event rates and effect-sizes for overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), distant metastasis-free survival and distant recurrence-free interval (DMFS/DMFI) and locoregional recurrence (LRR) as investigated endpoints. Furthermore, we compared selected acute and late toxicities in the included studies. Statistical analysis was performed using the Microsoft Excel (Microsoft, Redmont, WA, USA) add-in MetaXL 5.3 (EpiGear International, Sunrise Beach, Australia), utilizing the inverse variance heterogeneity model., Results: We identified six studies (n = 1280 patients) randomizing HFX-RT alone and the concurrent addition of CTx. OS was significantly improved in the HFX-RT + CTx group (HR = 0.77, CI95% = 0.66-0.89; p = <0.001). We found similar results in PFS (HR = 0.74, CI95% = 0.63-0.87; p < 0.001) and CSS (HR = 0.72, CI95% = 0.60-0.88; p = 0.001). In contrast, acute toxicities (≥grade 3 mucositis, ≥grade 3 dysphagia) and late adverse events including ≥grade 3 xerostomia, ≥grade 3 subcutaneous, ≥grade 3 bone, ≥grade 3 skin toxicity, and ≥grade 3 dysphagia did not significantly differ between the two groups., Conclusion: The addition of CTx to HFX-RT in the definitive treatment of advanced LA-HNSCC improves OS, CSS, PFS, and LRR without a significant increase in high-grade acute and late toxicities.

Purpose: To appraise the ability of a radiomics signature to predict clinical outcome after definitive radiochemotherapy (RCT) of stage III-IV head and neck cancer., Methods: A cohort of 110 patients was included in a retrospective analysis. Radiomics texture features were extracted from the gross tumor volumes contoured on planning computed tomography (CT) images. The cohort of patients was randomly divided into a training (70 patients) and a validation (40 patients) cohorts. Textural features were correlated to survival and control data to build predictive models. All the significant predictors of the univariate analysis were included in a multivariate model. The quality of the models was appraised by means of the concordance index (CI)., Results: A signature with 3 features was identified as predictive of overall survival (OS) with CI = 0.88 and 0.90 for the training and validation cohorts, respectively. A signature with 2 features was identified for progression-free survival (PFS; CI = 0.72 and 0.80); 2 features also characterized the signature for local control (LC; CI = 0.72 and 0.82). In all cases, the stratification in high- and low-risk groups for the training and validation cohorts led to significant differences in the actuarial curves. In the validation cohort the mean OS times (in months) were 78.9 ± 2.1 vs 67.4 ± 6.0 in the low- and high-risk groups, respectively, the PFS was 73.1 ± 3.7 and 50.7 ± 7.2, while the LC was 78.7 ± 2.1 and 63.9 ± 6.5., Conclusion: CT-based radiomic signatures that correlate with survival and control after RCT were identified and allow low- and high-risk groups of patients to be identified.

Purpose: The second primary cancer (SPC) incidence after treatment with platinum-based chemotherapy and cetuximab in combination with radiotherapy has not been previously reported. Our aim was to compare SPC risk following radiotherapy in combination with these agents for the treatment of head and neck squamous cell carcinoma (HNSCC)., Methods: The charts of 296 cases treated for loco-regionally advanced HNSCC between 2009 and 2015 were retrospectively reviewed for patient, tumor, and procedural characteristics. All patients were planned to undergo radiotherapy either with platinum compounds (group: Platinum) or monoclonal antibody cetuximab (group: Cetuximab). A third group of patients switched from platinum compounds to cetuximab due to toxicity (group: Switch). Treatment groups were evaluated for the incidence of SPC with log-rank test. Possible confounders were investigated with multivariate Cox's proportional hazards model. All tests were two-sided, and a p < 0.05 was set to indicate statistical significance., Results: Median follow-up was 36 months. Platinum, Cetuximab, and Switch groups consisted of 158, 101, and 37 patients, respectively. Three-year overall survival in the whole cohort was 70%. The rate of SPC was comparable between Platinum (9.2%) and Cetuximab (11.5%) groups (p = 0.98), whereas the patients in the Switch group were exposed to a significantly higher incidence of SPC (23.3%) in 3 years (p = 0.01). The multivariate model indicated Switch to be the only variable correlating with an increased risk for SPC., Conclusions: The Switch strategy may expose the patients to an increased risk of developing SPC. The use of switch should be advocated with caution until robust pre-clinical and clinical data are available.

Background: Cochlea sparing can reduce late ototoxicity in head and neck cancer patients treated with cisplatin-based radiochemotherapy. In this situation, a mean cochlear dose (MCD) constraint of 10 Gy has been suggested by others based on the dose-effect relationship of clinical data. We aimed to investigate whether this is feasible for primary and postoperative radiochemotherapy in locoregionally advanced tumors without compromising target coverage., Patients and Methods: Ten patients treated with definitive and ten patients treated with adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy were investigated. The cochleae and a planning risk volume (PRV) with a 3 mm margin were newly delineated, whereas target volumes and other organs at risk were not changed. The initial plan was recalculated with a constraint of 10 Gy (MCD) on the low-risk side. The quality of the resulting plan was evaluated using the difference in the equivalent uniform dose (EUD)., Results: A unilateral MCD of below 10 Gy could be achieved in every patient. The mean MCD was 6.8 Gy in the adjuvant cohort and 7.6 Gy in the definitive cohort, while the non-spared side showed a mean MCD of 18.7 and 30.3 Gy, respectively. The mean PRV doses were 7.8 and 8.4 Gy for the spared side and 18.5 and 29.8 Gy for the non-spared side, respectively. The mean EUD values of the initial and recalculated plans were identical. Target volume was not compromised., Conclusion: Unilateral cochlea sparing with an MCD of less than 10 Gy is feasible without compromising the target volume or dose coverage in locoregionally advanced head and neck cancer patients treated with IMRT. A prospective evaluation of the clinical benefit of this approach as well as further investigation of the dose-response relationship for future treatment modification appears promising.

Background: For head and neck squamous cell cancer (HNSCC), standard therapy consists of surgery, radiation, and/or chemotherapy. Antineoplastic immunotherapy could be an option in an adjuvant setting and is already in palliation. A functional immune system is a prerequisite for successful immunotherapy. However, effects of the standard-of-care therapy on the patients' immune system are not fully understood., Methods: Peripheral blood mononuclear cells (PBMC) were collected from patients with HNSCC (n = 37) and healthy controls (n = 10). PBMC were stimulated with staphylococcal enterotoxin B (SEB). Simultaneous expression of various cytokines was measured in CD4 + and CD8 + T cells by multicolor flow cytometry, and polyfunctional cytokine expression profiles were determined on a single-cell basis., Results: Expression levels of all measured cytokines in CD4 + T cells were higher in patients after chemoradiotherapy (CRT) as compared to untreated HNSCC patients or normal controls. After CRT, the frequency of polyfunctional CD4 + T cells, which simultaneously expressed multiple cytokines, was significantly increased as compared to untreated patients (p < 0.01)., Conclusion: CRT increases polyfunctionality of CD4 + T cells in HNSCC patients, suggesting that standard-of-care therapy can promote immune activity in immune cells. These polyfunctional CD4 + T cells in the blood of treated HNSCC patients are expected to be responsive to subsequent immunotherapeutic approaches.

Objectives: The study aimed to investigate the impact of chemoradiotherapy (CRT) on speech and voice quality according to the anatomic localization of the head and neck cancer., Methods: Thirty-four patients treated by CRT for advanced suprahyoid (N = 17) or infrahyoid (N = 17) cancer were assessed for speech function, videolaryngostroboscopy, Voice Handicap Index, blinded Grade, Roughness, Breathiness, Asthenia, Strain, and Instability, acoustic measurements, and aerodynamic measurements. Quality of life was evaluated using the European Organization for Research and Treatment of Cancer Head and Neck 35 (EORTC QLQ-H&N35) questionnaire., Results: Patients treated for an infrahyoid tumor presented more severe values of Voice Handicap Index items, dysphonia, breathiness, asthenia, and some acoustic cues (Voice Turbulence Index, Soft Phonation Index, degree of unvoiced segments, and number of unvoiced segments) than patients treated for a suprahyoid tumor. The EORTC QLQ-H&N35 communication item was better in the suprahyoid patient group., Conclusions: Voice quality impairments associated with CRT are more severe in patients treated for advanced infrahyoid cancer, suggesting the need to develop specific posttherapy management of the dysphonia according to the tumor anatomical localization., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cetuximab (CET) is a potent inhibitor of the epidermal growth factor receptor and has been shown to have activity in squamous cell carcinoma of the head and neck (SCCHN). We conducted a single-arm phase II trial of a combination therapy comprising cisplatin (CIS), CET and hyperfractionated accelerated radiotherapy (HART)., Patients and Methods: Patients with UICC stage III or IVA/B, M0 SCCHN were enrolled and treated with an initial dose of CET (400 mg/m 2 ) and then with a weekly dosage of 250 mg/m 2 during HART. HART was started with a prescribed dosage of 2.0 Gy per day for 3 weeks, followed by 1.4 Gy twice daily to a total dose of 70.6 Gy to the gross tumour volume. CIS (40 mg/m 2 ) was administered weekly (days 1, 8, 15, 22, 29 and 36). The primary objective of the phase II study was to determine the 2‑year progression-free survival (PFS)., Results: Between November 2007 and November 2010, a total of 74 patients were enrolled in the study, of whom 65 were evaluable (83% were men). Median age was 56 years (range 37-69 years). An Oropharyngeal primary tumour was diagnosed in 49%, T4a,b in 65% and N2/3 in 96% of the patients. Of these patients, 85% were smokers or ex-smokers. Complete remission (CR) was observed in 23 patients (35%). The most common toxicity grade was ≥3, including mucositis (58%) and dysphagia (52%). The 2‑ and 5‑year overall survival rates were 64 and 41%, the 2‑ and 5‑year PFS rates were 45 and 32%, and the 2‑ and 5‑year locoregional control rates were 47 and 33%, respectively., Conclusion: The combination of weekly CIS with HART plus CET is a feasible regimen for these unfavourable smoking-induced cancers. However, the parallel US study (RTOG 0522) showed no advantage of the enhanced triple therapy compared to chemoradiotherapy alone.

Background: Head and neck paragangliomas are rare. They are usually slow-growing, benign, non-catecholamine secreting tumours, traditionally treated with surgical excision. Complications of surgical excision include lower cranial nerve palsies, stroke and death., Method: A retrospective case note analysis was conducted of patients with head and neck paragangliomas treated with a watch-and-scan policy from March 2003 to September 2015, and the relevant literature was reviewed., Results: Fifteen head and neck paragangliomas were identified. None of the patients developed a new lower cranial nerve palsy or progression of their presenting hearing loss during the follow-up period. Five patients displayed an increase in maximum linear dimension of 4 mm over an average of 57.4 months. A review of the literature showed that a watch-and-surveillance scan policy is evolving as a treatment option for head and neck paragangliomas without malignant risk factors., Conclusion: Readily available surveillance scanning in head and neck paragangliomas enables the monitoring of head and neck paragangliomas, which may allow for avoidance of major surgery.

Objectives/hypothesis: Dysphagia is one of the most significant side effects of the treatment of head and neck cancer. Residue and aspiration are two indicators of dysphagia, but aspiration is historically the only indicator of interest, because it may impact health outcomes. Clinicians have anecdotally used residue as another marker of swallowing dysfunction, but it is understudied. This project investigated the impact of aspiration versus residue on function and quality of life (QoL) in these patients., Study Design: Observational study., Methods: A total of 168 head and neck cancer survivors with moderate to severe dysphagia were enrolled in a randomized clinical trial comparing two swallow therapy interventions. Data at time of entry were used for the current study. A modified barium swallow study was done to compute Penetration-Aspiration Scale (PAS) scores, percentage oral residue, and percentage pharyngeal residue with three bolus consistencies (5 mL thin, nectar, and pudding). The Performance Status Scale (PSS) and the Head Neck Cancer Inventory (HNCI) questionnaires were administered. Data were analyzed to determine associations between aspiration and residue estimates with function and QoL scores., Results: Worsening aspiration and residue estimates were all correlated with decreased scores on the PSS functional scales (r = -0.190 to -0.324, P ≤ .031). However, only increasing residue estimates were significantly related to decreased patient-perceived QoL on the HNCI (r = -.178 to -.194, P < .046). This effect was more pronounced with oral versus pharyngeal residue., Conclusions: In this group of head and neck cancer survivors, penetration/aspiration and residue show independent effects. PAS affects functional status only, but residue affects both functional status and QoL. This study supports that residue should be considered a primary measurement of swallowing function and be a target for identification, treatment, and evaluation of swallowing., Level of Evidence: 2c. Laryngoscope, 127:1615-1621, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To illustrate complex interdisciplinary decision making and the utility of modern endovascular techniques in the management of patients with carotid blowout syndrome (CBS)., Study Designs: Retrospective chart review., Methods: Patients treated with endovascular strategies and/or surgical modalities were included. Control of hemorrhage, neurological, and survival outcomes were studied., Results: Between 2004 and 2014, 33 patients had 38 hemorrhagic events related to head and neck cancer that were managed with endovascular means. Of these, 23 were localized to the external carotid artery (ECA) branches and five localized to the ECA main trunk; nine were related to the common carotid artery (CCA) or internal carotid artery (ICA), and one event was related to the innominate artery. Seven events related to the CCA/ICA or innominate artery were managed with endovascular sacrifice, whereas three cases were managed with a flow-preserving approach (covered stent). Only one patient developed permanent hemiparesis. In two of the three cases where the flow-preserving approach was used, the covered stent eventually became exposed via the overlying soft tissue defect, and definitive management using carotid revascularization or resection was employed to prevent further hemorrhage. In cases of soft tissue necrosis, vascularized tissues were used to cover the great vessels as applicable., Conclusions: The use of modern endovascular approaches for management of acute CBS yields optimal results and should be employed in a coordinated manner by the head and neck surgeon and the neurointerventionalist., Level of Evidence: 4. Laryngoscope, 2016 127:383-390, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: There is a lack of research on the financial impacts that head and neck cancer has on caregivers., Objective: To explore the overall financial impact of head and neck cancer on caregivers; to describe the factors that mitigate this impact., Methods: Interviews with 31 caregivers (mean time caring: 5.7 years)., Results: Head and neck cancer had a considerable financial impact on caregivers. It resulted in out of pocket costs and caregivers and/or their relative/friend with cancer often became under- or un-employed. Caregivers with large debts or ongoing expenses appeared to be particularly vulnerable to cancer-related financial pressures. Finance related psychological stress was prevalent, although some caregivers hid their psychological difficulties from other people. Factors which help caregivers to mitigate financial distress included having private health insurance and being able to access to medical and/or social welfare benefits., Conclusions: Head and neck cancer can cause caregivers substantial financial and psychological distress. Distress may be mitigated by providing caregivers and their households with access to welfare benefits., Implications for Practice: Health professionals should be aware that head and neck cancer can have short and long-term financial consequences for caregivers and their families. Health professionals should refer patients and their caregivers to medical social workers who can help them with their financial issues. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Nasal type extranodal natural killer/T-cell lymphoma (ENKTL) is a rare lymphoma in the USA and Europe but endemic in East Asia and in areas of South and Central America. Clinically natural killer cell lymphomas are divided into three categories; nasal, non-nasal and aggressive lymphoma/leukemia subtypes. ENKTL, nasal type occurs in the nose and can extend to the upper aero-digestive tract as reported in this longitudinal case study. This is a longitudinal report of progress of a 14-year-old boy with ENKTL originating in the nasal cavity with subsequent extension and recurrence in the contralateral nose, nasopharynx, larynx and trachea presenting with varying degrees of respiratory problems and eventually, respiratory distress. Caregiver refusal of stem cell transplantation prompted an alternative diagnostic and therapeutic approach. Clinical course with recurrences, extensions and remissions over 6years with tailored endoscopic surgical treatment and radiochemotherapy is documented to present a guide in the multidisciplinary management of this rare disease., (Published by Elsevier Inc.)

Objectives: Comparisons of induction chemotherapy (IC) against upfront chemoradiation (CRT) for locally advanced head and neck cancer (LA-HNSCC) have demonstrated no differences except greater toxicity with IC. Effective induction regimens that are less toxic are therefore warranted. To inform future efforts with IC, we present our institutional experience comparing a less toxic IC regimen to CRT., Methods: We included patients with LA-HNSCC treated with organ-preservation CRT (+/-induction) between 2008 and 2011. Patients were of age above 18 years, ECOG performance status 0-1, and had minimum 6 months follow-up. IC consisted of 8 weekly cycles of cetuximab, carboplatin, and paclitaxel followed by CRT. The CRT regimen was platinum based, with cetuximab reserved for patients contraindicated to receive platinum., Results: Of 118 patients, 24 (20%) received IC and 94 (80%) received CRT. Median follow-up was 17 (IC) and 19 (CRT) months (P=0.05). There were no differences in toxicity between the groups. IC patients were more likely male, with more advanced tumor and nodal stage. Even when controlling for these factors, IC was still associated with worse locoregional control (HR=3.6, P=0.02), distant metastasis-free survival (HR=5.3, P=0.02), and overall survival (HR=5.1, P<0.01)., Conclusions: IC patients had greater disease burden than those receiving CRT. IC was well tolerated, but with significant rates of locoregional and systemic failures. Given the retrospective nature of the study, our findings are not meant to be definitive or conclusive, but rather suggestive in directing future efforts with IC. For now, we favor CRT as the standard option for treatment of inoperable LA-HNSCC., Competing Interests: notification: For the remaining authors, none were declared.

Background: Various subtypes of melanoma-associated antigens (MAGEs) are expressed in the tumor tissues of patients with head and neck squamous cell carcinoma (HNSCC). However, little data are currently available on how the gene expression of MAGEs impacts clinical patterns and oncologic outcomes. We have therefore evaluated the expression of MAGE-A1-6 (A1-6) subtypes in tumor tissues of patients with HNSCC and the clinical impact of this expression., Methods: This was a retrospective review of 53 patients with histologically proven HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx who underwent both treatment and analysis by reverse transcription (RT)-PCR assay with a common primer to identify the expression of MAGE-A1-6 subtypes in the tumor tissue. The clinicopathologic factors and oncologic outcomes of these patients and the correlations of both to MAGE-A1-6 gene expression were analyzed., Results: MAGE-A1-6 subtypes were expressed in the tumor tissues of 37 patients (69.8 %). Patient age of ≥65 years [p = 0.031, hazard ratio (HR) 4.866] and advanced American Joint Committee on Cancer stage (p = 0.035, HR 4.291) were independent risk factors for expression of MAGE-A1-6 subtypes. Patients with MAGE-A1-6 expression had lower disease-free survival (p = 0.029), disease-specific survival (p = 0.070), and overall survival (p = 0.017) rates. Overall survival rate was independently associated to chemotherapy (p = 0.011, HR 2.859), while no surgery (p = 0.050, HR 2.400) and MAGE-A1-6 expression (p = 0.050, HR 2.527) showed borderline significance., Conclusion: In our patient group the expression of MAGE-A1-6 subtypes in tumor tissues of patients with HNSCC was correlated with advanced clinical stage of cancer and poor oncologic outcomes. We suggest that gene expression of MAGE-A1-6 subtypes may be considered to be a predictive factor to determine patient treatment or follow-up strategy.

Background: For primary organ preservation, concurrent chemoradiotherapy (CCRT) is performed for advanced squamous cell carcinoma of the head and neck (SCCHN). In this organ-preservation setting with CCRT, surgery is reserved as a salvage treatment in cases of locoregional failure after CCRT. The purpose of the study was to review our experience with salvage surgery after CCRT for patients with SCCHN and to evaluate the effectiveness and prognostic factors affecting survival., Methods: The records of patients with stage II-IVB SCC of the larynx, oropharynx, or hypopharynx treated with salvage surgery after CCRT between 1998 and 2012 were reviewed., Results: A total of 645 patients with previously untreated, resectable SCC of the larynx, oropharynx, or hypopharynx received CCRT. Salvage surgery was performed for 78 of 225 patients with residual or recurrent tumors. The 5-year overall survival (OS) and disease-specific survival rates for patients who received salvage surgery were 61.0 and 65.5 %, respectively. Stage IV, poorly differentiated, synchronous double cancer, and surgical complications were significant predictors of unfavorable OS on multivariate analysis. Postoperative complications were observed in 30 patients (38.5 %)., Conclusions: Salvage surgery is the best therapeutic option for failure after CCRT for SCCHN because of its good survival rate, although a high surgical complication rate is seen. Patients with initial stage IV tumors, poorly differentiated SCC, or synchronous double cancer are considered for further adjuvant treatment.

Aim: To compare simultaneous integrated boost plans for intensity-modulated proton therapy (IMPT), helical tomotherapy (HT), and RapidArc therapy (RA) for patients with head and neck cancer., Patients and Methods: A total of 20 patients with squamous cell carcinoma of the head and neck received definitive chemoradiation with bilateral (n = 14) or unilateral (n = 6) neck irradiation and were planned using IMPT, HT, and RA with 54.4, 60.8, and 70.4 GyE/Gy in 32 fractions. Dose distributions, coverage, conformity, homogeneity to planning target volumes (PTV)s and sparing of organs at risk and normal tissue were compared., Results: All unilateral and bilateral plans showed excellent PTV coverage and acceptable dose conformity. For unilateral treatment, IMPT delivered substantially lower mean doses to contralateral salivary glands (< 0.001-1.1 Gy) than both rotational techniques did (parotid gland: 6-10 Gy; submandibular gland: 15-20 Gy). Regarding the sparing of classical organs at risk for bilateral treatment, IMPT and HT were similarly excellent and RA was satisfactory., Conclusion: For unilateral neck irradiation, IMPT may minimize the dry mouth risk in this subgroup but showed no advantage over HT for bilateral neck treatment regarding classical organ-at-risk sparing. All methods satisfied modern standards regarding toxicity and excellent target coverage for unilateral and bilateral treatment of head and neck cancer at the planning level.

Chemoradiotherapy (CRT) has evolved as the preferred organ preservation strategy in the treatment of locally advanced head and neck cancer (HNC). This approach increases malnutrition, and thus, establishing a direct enteral feeding route is essential. To evaluate the usefulness of prophylactic percutaneous endoscopic gastrostomy (PEG) in HNC patients receiving definitive CRT, we performed a prospective evaluation of HNC patients over a 6-month period. Patients and tumor characteristics, nutritional status 30 days after PEG insertion and technique complications were evaluated. We also assessed the long-term PEG usage. Forty-seven PEGs were placed and only 2 patients did not use it. The mean time of PEG use was 131 days (4-255) and mean duration of exclusive utilization was 71 days (4-180). On 30th day after procedure, 34/45 (76 %) patients had lost weight, but only 10/45 (22 %) patients had lost more than 10 % of their initial weight. The most frequent complications were minor peristomal infections, which were correlated with proton-pump inhibitor use before PEG placement (OR 3.91, 95 % CI 1.01-15.2, and p = 0.049). One year later, 19 % of patients in remission continue needing PEG. Enteric nutritional support is essential during and after CRT in HNC patients. Most patients lost weight even with PEG. One-fifth of patients in remission required long-term PEG utilization.

Objective: The chemokine CXCL12 and its receptor CXCR4 can affect tumor growth, recurrence, and metastasis. We tested the hypothesis that the CXCL12 and CXCR4 expression influences the prognosis of patients with inoperable head and neck cancer treated with definite radiotherapy or chemoradiotherapy., Methods: Formalin-fixed paraffin-embedded pretreatment tumor tissue from 233 patients with known HPV/p16(INK4A) status was analyzed. CXCL12 and CXCR4 expressions were correlated with pretreatment parameters and survival data by univariate and multivariate Cox regression., Results: CXCL12 was expressed in 43.3 % and CXCR4 in 66.1 % of the samples and both were correlated with HPV/p16(INK4A) positivity. A high CXCL12 expression was associated with increased overall survival (p = 0.036), while a high CXCR4 expression was associated with decreased metastasis-free survival (p = 0.034)., Conclusion: A high CXCR4 expression could be regarded as a negative prognostic factor in head and neck cancer because it may foster metastatic spread. This may recommend CXCR4 as therapeutic target for combating head and neck cancer metastasis.

Importance: Patients with head and neck cancer may experience chemoradiotherapy-induced hearing loss, but the weighing of involved variables has been subjective. Identification of patient and treatment characteristics to predict the absolute posttreatment hearing level is important for effective counseling of patients undergoing chemoradiotherapy., Objective: To predict treatment-induced hearing loss among patients with head and neck cancer., Design, Setting, and Participants: A retrospective cohort study was performed at The Netherlands Cancer Institute. One hundred and fifty-six patients with head and neck cancer treated with concomitant chemoradiotherapy as the primary treatment modality from January 1, 1997, through December 31, 2011, were enrolled. Follow-up was complete on March 1, 2012, and data were analyzed from April 1, 2011, through November 5, 2013., Interventions: High-dose intravenously administered cisplatin-based concomitant chemoradiotherapy. Cisplatin, 100 mg/m2, was administered in 3 courses on days 1, 22, and 43 during 7 weeks of radiotherapy (total radiation dose, 70 Gy in 35 fractions)., Main Outcomes and Measures: Posttreatment bone conduction hearing threshold at pure-tone average frequencies of 1, 2, and 4 kHz, based on pure-tone audiometry after completion of treatment. Predictors included baseline hearing levels, radiation dose to the cochlea, and cisplatin dose. A multilevel mixed-effects linear regression model for predicting whether or not posttreatment hearing was at least 35 dB was established, and cross-validated sensitivity and specificity were obtained., Results: Of 156 patients who received high-dose concomitant chemoradiotherapy, 15 were missing the exact radiation dose to the cochlea and 41 had no data on posttreatment pure-tone audiometry. Nineteen patients had a hearing level of at least 35 dB for at least 1 ear before the treatment. The remaining 81 patients (162 ears) had a total cumulative cisplatin dose ranging from 315 to 600 (median, 546) mg. The radiation dose to the cochlea ranged from 1.1 to 70.9 (median, 13.6) Gy. Based on data from the 81 patients (162 ears), the area under the receiver operating characteristic curve was 0.68, with a sensitivity of 29% (95% CI, 13%-51%) and a specificity of 97% (95% CI, 88%-100%), resulting in a positive predictive value of 78%., Conclusions and Relevance: Patient and treatment characteristics can be used to predict hearing level after concomitant chemoradiotherapy for head and neck cancer. This step may constitute the first in evidence-based individual counseling for treatment-induced hearing loss.

Importance: The US veteran population represents a unique cohort of patients in whom human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has yet to be investigated., Objective: To investigate the incidence and characteristics of HPV-positive HNSCC within the veteran population., Design, Setting, and Participants: Retrospective medical record review including patients with HNSCC diagnosed between January 1, 2010, and November 15, 2013, from the VA Greater Los Angeles Healthcare System. Data were collected between November 16, 2013, and June 19, 2014, and analyzed between June 20, 2014, and March 26, 2015., Exposures: Chemoradiation therapy, radiation therapy, surgery, or no treatment., Main Outcomes and Measures: We determined HPV positivity by p16 testing. Demographic and clinicopathologic information and overall survival were extracted from medical records., Results: We identified 150 patients with the diagnosis of HNSCC. Sixty-nine patients had HPV-positive tumors (46%), and 65 (43%) had HPV-negative tumors (16 did not have HPV testing). Age at diagnosis ranged from 44 to 94 years (mean, 64.6 [SD, 8.0] years), and median (interquartile range) follow-up was 16.7 (8.7-27.3) years. Tumor location differed significantly between the 2 groups, with an HPV-positive predominance in the oropharynx (43 of 57 [75%]; P < .001). The HPV-positive patients were more likely to be treated primarily with combined chemoradiation therapy than radiation therapy or surgery (P < .001). T4 tumors had a nearly 9 times greater rate of mortality compared with T1 tumors (HR, 8.52 [95% CI, 2.60-18.40; P < .001); N3 disease was associated with 7.18 times greater mortality (HR, 7.18 [95% CI, 1.99-12.26]; P < .001) compared with N1 disease; and M1 disease was associated with 6.0 times greater mortality (HR, 5.99 [95% CI, 2.59-13.81]; P < .001). There were 42 total deaths during follow-up, 25 in the HPV-negative group and 17 in the HPV-positive group, with a nonsignificantly higher overall survival among HPV-positive patients independent of alcohol or tobacco use history (P = .09)., Conclusions and Relevance: Previous studies have found that the proportion of HPV-positive HNSCC in the general population ranges between 20% and 75%. Although the incidence of HPV-positive HNSCC in the Veterans Affairs population is comparable, these patients have unique risk factors and demographic characteristics that may suggest different prognostic factors for HPV-positive HNSCC in this population. Nonetheless, HPV-positive tumors still seem to portend a better overall prognosis regardless of alcohol or tobacco history among the Veterans Affairs population.

Background: Multimodal treatment options in head and neck squamous cell carcinoma have allowed for greater control of locoregional disease, but this has not translated into a significant overall survival advantage for patients. This is partially because these treatment modalities have no influence over the rate of development of distant metastases., Objective: This article summarises the current methods of detecting circulating and disseminated tumour cells. It also discusses how these cells can offer prognostic value in head and neck squamous cell carcinoma, and considers questions posed by the identification of these cells., Methods: A literature search of relevant journal articles was performed using ScienceDirect and PubMed databases, and a general article search was conducted using the online search engine Google., Results and Conclusion: The evidence presented in this article indicates that circulating tumour cells and disseminated tumour cells may be clinically useful as prognostic markers or in the assessment of response to treatment in head and neck squamous cell carcinoma.

Purpose: Concurrent chemoradiotherapy (CRT) is the standard treatment for advanced head and neck squamous cell carcinoma. In this phase II randomized study, the efficacy and toxicity of docetaxel, cisplatin and 5-fluorouracil induction chemotherapy (ICT) followed by concurrent CRT was compared with those after standard CRT alone in patients with locally advanced, unresectable head and neck cancer., Patients and Methods: Between January 2007 and June 2009, 66 patients with advanced (stage III or IV) unresectable squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, and larynx) were randomly assigned to two groups: one receiving two cycles of docetaxel, cisplatin, and 5-fluorouracil ICT followed by CRT with three cycles of cisplatin and one treated by CRT alone. Response rate, local tumor control (LTC), locoregional tumor control (LRTC), overall survival (OS), progression-free survival (PFS), and toxicity results were assessed., Results: Three patients from the ICT + CRT group did not appear at the first treatment, so a total of 63 patients were evaluated in the study (30 ICT + CRT group and 33 CRT group). Three patients died of febrile neutropenia after ICT. The median follow-up time for surviving patients was 63 months (range 53-82 months). The rate of radiologic complete response was 63% following ICT + CRT, whereas 70% after CRT alone. There were no significant differences in the 3-year rates of LTC (56 vs. 57%), LRTC (42 vs. 50%), OS (43 vs. 55%), and PFS (41 vs. 50%) in the ICT + CRT group and in the CRT group, respectively. The rate of grade 3-4 neutropenia was significantly higher in the ICT + CRT group than in the CRT group (37 and 12%; p = 0.024). Late toxicity (grade 2 or 3 xerostomia) developed in 59 and 42% in the ICT + CRT and CRT groups, respectively., Conclusion: The addition of ICT to CRT did not show any advantage in our phase II trial, while the incidence of adverse events increased. The three deaths as a consequence of ICT call attention to the importance of adequate patient selection if ICT is considered.

Purpose: Locoregional recurrence remains the main pattern of failure after primary combined modality treatment of squamous cell carcinoma of the head and neck (SCCHN). We compared the efficacy and toxicity of either cisplatin or cetuximab in combination with re-irradiation (ReRT) for recurrent unresectable SCCHN. Various clinicopathological factors were investigated to establish a prognostic score., Patients and Methods: Between 2007 and 2014, 66 patients with recurrent SCCHN originating in a previously irradiated area received cetuximab (n = 33) or cisplatin-based chemotherapy (n = 33) concomitant with ReRT. Toxicity was evaluated weekly and at every follow-up visit. Physical examination, endoscopy, CT or MRI scans were used to evaluate response and disease control., Results: With a mean follow-up of 18.3 months, the 1-year overall survival (OS) rates for Re-RT with cetuximab and cisplatin-based chemotherapy were 44.4 and 45.5% (p = 0.352), respectively. At 1 year, local control rates (LCR) were 46.4 and 54.2% (p = 0.625), freedom from metastases (FFM) rates 73.6 and 81% (p = 0.842), respectively. Haematological toxicity ≥ grade 3 occurred more often in the cisplatin group (p < 0.001), pain ≥ grade 3 was increased in the cetuximab group (p = 0.034). A physiological haemoglobin level and a longer interval between primary RT and ReRT, proved to be significant prognostic factors for OS (multivariate: p = 0.003, p = 0.002, respectively). Site of the recurrence and gross target volume (GTV) did not show a significant impact on OS in multivariate analysis (p = 0.160, p = 0.167, respectively). A prognostic-score (1-4 points) based on these four variables identified significantly different subgroups: 1-year OS for 0/1/2/3/4 prognostic points: 10, 38, 76, 80 and 100%, respectively (p < 0.001)., Conclusion: Both cetuximab- and cisplatin-based ReRT of SCCHN recurrences are feasible and effective treatment options with comparable results in terms of tumour control and survival. Acute adverse events may differ slightly. Our prognostic score could help to identify appropriate patients for ReRT and stratify patients within future clinical trials.

Background: Haemoptysis is an uncommon presenting symptom to the ENT clinic and ward, but has potentially sinister aetiology. This article aims to provide a systematic and evidence-based method of managing patients with haemoptysis., Methods: The data in this article are based on a literature search performed using PubMed in August 2013. The keywords used included 'haemoptysis' in combination with 'otolaryngology', 'ENT', 'head & neck', 'diagnosis', 'management', 'investigations' and 'treatment'., Results: The majority of published literature on the subject is level IV evidence. However, this can guide ENT specialists in assessing, investigating and managing presentations of haemoptysis., Conclusion: Understanding the different causes of haemoptysis is important for the otolaryngologist. The main concern is the detection of a malignant lesion in the upper aerodigestive tract or tracheobronchial tree. A thorough history and systematic examination can aid diagnosis.

Background: Superior treatment response and survival for patients with human papilloma virus (HPV)-positive head and neck cancer (HNSCC) are documented in clinical studies. However, the relevance of high-grade acute organ toxicity (HGAOT), which has also been correlated with improved prognosis, has attracted scant attention in HPV-positive HNSCC patients. Hence we tested the hypothesis that both parameters, HPV and HGAOT, are positive prognostic factors in patients with HNSCC treated with definite radiotherapy (RT) or radiochemotherapy (RCT)., Patients and Methods: Pretreatment tumor tissue and clinical records were available from 233 patients receiving definite RT (62 patients) or RCT (171 patients). HPV infection was analysed by means of HPV DNA detection or p16(INK4A) expression; HGAOT was defined as the occurrence of acute organ toxicity >grade 2 according to the Common Toxicity Criteria. Both variables were correlated with overall survival (OS) using Cox proportional hazards regression., Results: Positivity for HPV DNA (44 samples, 18.9 %) and p16(INK4A) expression (102 samples, 43.8 %) were significantly correlated (p < 0.01), and HGAOT occurred in 77 (33 %) patients. Overall, the 5-year OS was 23 %; stratified for p16(INK4A) expression and HGAOT, OS rates were 47 %, 42 %, 20 % and 10 % for patients with p16(INK4A) expression and HGAOT, patients with HGAOT only, patients with p16(INK4A) expression only, and patients without p16(INK4A) expression or HGAOT, respectively. After multivariate testing p16(INK4A) expression (p = 0.003) and HGAOT (p < 0.001) were significantly associated with OS., Conclusion: P16(INK4A) expression and HGAOT are independent prognostic factors for OS of patients with HNSCC, whereas p16(INK4A) expression is particularly important for patients without HGAOT.

Background: The management of patients with advanced stages of head and neck cancer requires a multidisciplinary and multimodality treatment approach which includes a combination of surgery, radiation, and chemotherapy. These toxic treatment protocols have significantly improved survival outcomes in a distinct population of human papillomavirus (HPV) associated oropharyngeal cancer. HPV negative head and neck squamous cell carcinoma (HNSCC) remains a challenge to treat because there is only a modest improvement in survival with the present treatment regimens, requiring innovative and new treatment approaches. Oncolytic viruses used as low toxicity adjunct cancer therapies are novel, potentially effective treatments for HNSCC. One such oncolytic virus is Respiratory Orphan Enteric virus or reovirus. Susceptibility of HNSCC cells towards reovirus infection and reovirus-induced cell death has been previously demonstrated but has not been compared in HPV positive and negative HNSCC cell lines., Objectives: To compare the infectivity and oncolytic activity of reovirus in HPV positive and negative HNSCC cell lines., Methods: Seven HNSCC cell lines were infected with serial dilutions of reovirus. Two cell lines (UM-SCC-47 and UM-SCC-104) were positive for type 16 HPV. Infectivity was measured using a cell-based ELISA assay 18 h after infection. Oncolytic activity was determined using an alamar blue viability assay 96 h after infection. Non-linear regression models were used to calculate the amounts of virus required to infect and to cause cell death in 50% of a given cell line (EC50). EC50 values were compared., Results: HPV negative cells were more susceptible to viral infection and oncolysis compared to HPV positive cell lines. EC50 for infectivity at 18 h ranged from multiplicity of infection (MOI) values (PFU/cell) of 18.6 (SCC-9) to 3133 (UM-SCC 104). EC50 for cell death at 96 h ranged from a MOI (PFU/cell) of 1.02×10(2) (UM-SCC-14A) to 3.19×10(8) (UM-SCC-47). There was a 3×10(6) fold difference between the least susceptible cell line (UM-SCC-47) and the most susceptible line (UM-SCC 14A) EC50 for cell death at 96 h., Conclusions: HPV negative HNSCC cell lines appear to demonstrate greater reovirus infectivity and virus-mediated oncolysis compared to HPV positive HNSCC. Reovirus shows promise as a novel therapy in HNSCC, and may be of particular benefit in HPV negative patients.

Aim: The goal of the present work was to compare outcomes of definitive concurrent cisplatin-based chemoradiotherapy (CRT) with cetuximab-based bioradiotherapy (BRT) in locally advanced head-and-neck squamous cell carcinoma (HNSCC)., Patients and Methods: Between 2006 and 2012, 265 patients with locally advanced HNSCC were treated at our institution with CRT (n = 194; 73%) with three cycles of cisplatin (100 mg/m(2), every 3 weeks) or BRT (n = 71; 27%) with weekly cetuximab. Patients receiving BRT had more pre-existing conditions (Charlson index ≥ 2) than the CRT group (p = 0.005)., Results: Median follow-up was 29 months. In all, 56% of patients treated with CRT received the planned three cycles (92% at least two cycles) and 79% patients treated with BRT received six cycles or more. The 2-year actuarial overall survival (OS) and progression-free survival (PFS) were 72% and 61%, respectively. In the multivariate analysis (MVA), T4 stage, N2-3 stage, smoking status (current smoker as compared with never smoker), and non-oropharyngeal locations predicted for OS, whereas BRT association with OS was of borderline significance (p = 0.054). The 2-year actuarial locoregional control (LRC) and distant control (DC) rates were 73 and 79%, respectively. CRT was independently associated with an improved LRC (2-year LRC: 76% for CRT vs. 61% for BRT) and DC (2-year LRC: 81% for CRT vs. 68% for BRT) in comparison with BRT (p < 0.001 and p = 0.01 in the MVA). Subgroup analyses showed that T4 patients benefited significantly from CRT (vs. BRT) in LRC, while T1-3 did not. BRT patients had more G3-4 skin complications (p < 0.001) and CRT patients had higher rates of feeding tube placement (p = 0.006) and G3-4 gastrointestinal toxicities (p < 0.001)., Conclusion: This retrospective analysis showed a better LRC in locally advanced HNSCC treated by cisplatin-based CRT than cetuximab-based BRT, and a nonsignificant trend towards an improved OS.

Background: HPV-infection, p16 positivity, and EGFR expression have been correlated with favorable responses of head and neck cancer patients treated with radiotherapy (RT) with or without chemotherapy. However, a possible correlation of HPV/p16 and EGFR status on the effect of RT in combination with cetuximab has not been sufficiently investigated., Materials and Methods: We analyzed tumor samples for p16 and EGFR expression and correlated these variables with treatment outcome. Cox-proportional-hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. Survival was estimated by the Kaplan-Meier method. Results were compared with an institutional historical control group treated without cetuximab and with published data., Results: Expression of p16 was predominantly found in oropharyngeal squamous cell cancer patients (OPSCC; 36.6% positivity; 92% of all cases), while EGFR was expressed at high levels in all tumor subsites (82%). p16 expression was associated with improved overall survival in irradiated OPSCC patients (2-year overall survival of 80% in p16-positive vs. 33% overall survival in p16-negative patients). In a multivariable analysis covering all tumor sites, nodal stage (> N2a vs. ≤ N2a) and tumor site (OPSSC vs. non-OPSCC) had an impact on overall survival., Conclusion: Our results show that p16 positivity is associated with a favorable outcome in OPSCC patients treated with RT and cetuximab.

Carcinoma of unknown primary of the neck (CUP) is a metastasis presenting in one or more cervical lymph nodes, with no primary mucosal site identified. Retrospective case notes review of 25 consecutive patients (median age 55, 72% males) diagnosed as CUP who underwent neck dissection in a UK tertiary referral comprehensive cancer centre between 2000 and 2011. Median follow-up was 33 months. Nineteen patients underwent comprehensive neck dissections (six extended), six patients had selective neck dissection. Five year disease specific survival and regional recurrence free survival were 76 and 80% respectively. The overall rate of occult disease (disease not identified on preoperative evaluation, but found on histopathologic examination) was 8%, with rates of 0% in level I and 6% in level V. Our study suggests that in patients without preoperative evidence of disease in levels I or V selective neck dissection might be considered as an option, to facilitate preservation of the submandibular gland and accessory nerve without compromising oncological outcome. Larger studies should be performed before a change in practice can be advised.

The objective of the study was the assessment of the results of a prospective clinical trial with two preventive swallowing rehabilitation programs on the long-term side effects of chemoradiotherapy (CCRT) in advanced head and neck cancer patients. The study cohort consisted of 29 patients, randomized in two exercise groups: a standard (S) group receiving routine swallowing exercises (N = 14), and an experimental (E) group receiving swallowing exercises based on the TheraBite® Jaw Motion Rehabilitation System™ (N = 15). Assessment of functional changes was carried out with multidimensional outcome measures (e.g., videofluoroscopy, study-specific questionnaires) at four time points (pre-treatment, at 10 weeks, 1 year, and 2 years post-treatment). Overall, in the first year post-treatment many initial tumor- and treatment-related problems diminished significantly, except xerostomia (59%). The only additional improvement at 2 years was that the overall weight significantly further increased (p = 0.000), however, without regaining baseline value. In the subgroup analysis according to exercise group, this difference was significant in the E-group only (p = 0.002). The same was the case for the subgroup analysis according to site of disease, with a significant weight gain in the 'below the hyoid bone' group only. This study shows that the overall functional problems at 1 and 2 years post-CCRT are limited. Both rehabilitation programs produce similar results, with a slight but significant benefit for the E-group in weight gain at 2 years, as also seen in the 'below the hyoid bone' group. Both rehabilitation programs applied are feasible and show good compliance despite the burdensome CCRT.

Purpose: Despite the lack of evidence to support its implementation in the clinical practice, induction chemotherapy (IC) before chemoradiotherapy (CRT) is often used in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). We retrospectively examined the tolerability, feasibility, and clinical outcome of both concepts in a single center analysis., Patients and Methods: In all, 83 patients were treated between 2007 and 2010 with IC + CRT (n = 42) or CRT alone (n = 41). IC consisted of docetaxel, cisplatin and 5-fluorouracil (TPF), or cisplatin and 5-fluorouracil (PF). All patients were scheduled to receive 2 cycles of PF during concurrent CRT. Adverse events were assessed according to the common toxicity criteria of adverse events (CTCAE v. 3.0). Associations were tested using the χ² test, and survival estimates were calculated according to Kaplan-Meier., Results: The median follow-up was 30.35 months (range 2.66-61.25 months). At 2 years, the overall survival rate was significantly higher for primary CRT compared to IC + CRT group (74.8 % vs. 54 %, respectively; p = 0.041). Significantly more treatment-related overall grade 4 toxicities were documented in the IC + CRT group compared to the CRT group (42.9% vs. 9.8%; p = 0.001). Renal toxicity ≥ grade 2 occurred in 52.4 % vs. 7.3 % (p < 0.001), respectively. In all, 93 % of the patients with primary CRT compared to 71 % with IC + CRT received the planned full radiotherapy dose (p = 0.012)., Conclusion: This is, to our knowledge, the largest retrospective study to compare IC + CRT with primary CRT. IC showed high acute toxicity, compromised the feasibility of concurrent CRT, and was associated with reduced overall survival rates compared to primary CRT. The lack of clinical benefit in conjunction with the increased toxicity does not support implementation of IC.

Purpose: In this study, the acute toxicity and long-term outcome of a hyperfractionated accelerated chemoradiation regimen with cisplatin/5-fluorouracil (5-FU) in patients with locally advanced squamous cell carcinomas of head and neck were evaluated., Patients and Methods: From 2000-2002, 38 patients with stage III (5.3 %) and stage IV (94.7 %) head and neck cancer were enrolled in a phase II study. Patients received hyperfractionated-accelerated radiotherapy with 72 Gy in 15 fractions of 2 Gy followed by 1.4 Gy twice daily with concurrent, continuous infusion 5-FU of 600 mg/m(2) on days 1-5 and 6 cycles of weekly cisplatin (30 mg/m(2)). Acute toxicities (CTCAEv2.0), locoregional control (LRC), metastases-free (MFS), and overall survival (OS) were analyzed and exploratively compared with the ARO 95-06 trial., Results: Median follow-up was 11.4 years (95 % CI 8.6-14.2) and mean dose 71.6 Gy. Of the patients, 82 % had 6 (n = 15) or 5 (n = 16) cycles of cisplatin, 5 and 2 patients received 4 and 3 cycles, respectively. Grade 3 anemia, leukopenia, and thrombocytopenia were observed in 15.8, 15.8, and 2.6 %, respectively. Grade 3 mucositis in 50 %, grade 3 and 4 dysphagia in 55 and 13 %. The 2-, 5-, and 10-year LRC was 65, 53.6, and 48.2 %, the MFS was 77.5, 66.7, and 57.2 % and the OS 59.6, 29.2, and 15 %, respectively., Conclusion: Chemoradiation with 5-FU and cisplatin seems feasible and superior in terms of LRC and OS to the ARO 95-06C-HART arm at 2 years. However, this did not persist at the 5- and 10-year follow-ups.

Based on a review of the indexed medical literature (PubMed database), the authors describe the clinical features leading to the diagnosis of first bite syndrome, the pathophysiology of this syndrome and analyse the various treatment options available to otorhinolaryngologists to manage this syndrome., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

The aim of this study was to perform a systematic literature review of Merkel cell carcinomas (MCCs) originating exclusively in the ear, nose and throat (ENT) district. An appropriate string was run on PubMed to retrieve articles dealing with ENT presentations of MCC. A double cross-check was performed on citations and full-text articles found using the selected inclusion and exclusion criteria. In total, 43 articles were finally included in the study, describing 51 cases of MCC involving the ENT region: 22/51 (43%) cases involving the ear; 20/51 (39%) cases involving the mucosal sites; 9/51 (18%) cases involving other ENT regions. Patients with mucosal site involvement showed a higher mortality rate from the disease (45%) in comparison with the other two groups, especially when compared with those patients having primary involvement of the ear (22%). The ENT specialist should suspect and consider MCC, especially in elderly patients presenting with a suspicious lesion of the auricular pavilion, so as to avoid misdiagnosis and delayed treatments.

Background: Esophageal cancer is frequently associated with head and neck cancer, and esophagectomy is usually difficult in such a case. The purpose of this study was to clarify the clinical significance of esophagectomy for patients with esophageal cancer associated either synchronously or metachronously with head and neck cancer., Methods: The clinical outcomes of surgical resections for esophageal cancer were compared between 26 patients with head and neck cancer (double cancer group) and 176 without head and neck cancer (control group)., Results: Staged operations were performed in 5 patients in the double cancer group, while microvascular anastomosis as well as a muscle flap was added for 3 and 4 patients, respectively. The mortality and morbidity of the double cancer group were 0 and 35 %, respectively, which were not significantly different from those of the control group (3 and 31 %, respectively). There were no significant differences in overall survival in the double cancer and control groups, which had 5-year survival rates of 59 and 49 %, respectively., Conclusions: Esophagectomy can be an effective treatment when techniques are adopted that are appropriate for each case, such as staged operations, muscular flaps, and microvascular anastomosis, even in patients with double cancers of the esophagus and the head and neck.

Conclusion: Head and neck cancer (HNC) incidence and mortality trends in men displayed a significant downward trend in Croatia during the study period. No significant changes of incidence and mortality trends were observed in women. Decreasing trends observed in men are similar to other European countries. Further decreases in HNC incidence and mortality could be achieved with more restrictive alcohol and tobacco control policies and adherence to national treatment guidelines., Objective: To describe and interpret trends in incidence and mortality of HNC in Croatia in the period 1988-2008., Methods: HNCs were defined as ICD-10 codes C00-C14, C32. Incidence data were obtained from the Croatian National Cancer Registry, while numbers of deaths were obtained from the WHO Mortality Databank. Joinpoint regression analysis of age-standardized rates (ASR, standard world population) and age-specific rates for 10-year age groups was used to estimate changes in trends of HNC incidence and mortality., Results: HNC incidence and mortality in men declined steadily during the study period (estimated annual percent change (EAPC) of -1.5% and -1.8%, respectively). The most prominent decreases of -5.7% annually for incidence and -9.3% for mortality were observed in the youngest age group, 30-39 years. A non-significant increase in incidence (EAPC 0.9%) and decrease in mortality (EAPC -1.3%) were observed in women.

Objective: To compare incidence, stage, and survival of upper aerodigestive tract (UADT) cancers in patients with and without chronic lymphocytic leukemia (CLL)., Design: Inception cohort., Setting: National database., Patients: Individuals with CLL and UADT cancers included in the Surveillance, Epidemiology, and End Results (SEER) database., Main Outcome Measures: Incidence was compared by computing standardized incidence ratio (SIR), the ratio of observed UADT cancers in patients with CLL, and the number of UADT cancers expected based on the characteristics of patients with CLL and population incidence of UADT cancers. The association between CLL and UADT cancer stage was measured using odds ratio (OR) calculations. Survival of patients with UADT cancer with and without CLL was compared., Results: For the SIR calculation, 36 985 patients with CLL contributed a mean 6.36 years of follow-up each, for a total of 235 314 person-years of follow-up. The SIR was 1.18 (95% CI, 0.97-1.41) for UADT cancers; 1.52 (95% CI, 1.18-1.93) for laryngeal cancer; and 1.92 (95% CI, 1.05-3.23) for cancers of the nasal cavity and paranasal sinuses. In the stage and survival analyses, 253 patients with CLL followed by a UADT cancer were compared with 133 840 patients with 1 UADT cancer only. Cancers of the UADT in patients with CLL were more likely localized (OR, 0.50; 95% CI, 0.37-0.68). Relative survival was worse in patients with CLL. In multivariate analysis, CLL was independently associated with poorer observed survival (hazard ratio, 1.45; 95% CI, 1.24-1.70)., Conclusions: Larynx and nasal cavity cancers were more common in patients with CLL. Overall incidence of UADT cancers was not significantly elevated. Cancers of the UADT in patients with CLL were more likely to be localized at diagnosis than those in patients without CLL. Finally, CLL was associated with poorer survival outcomes.

Conclusion: Despite low uptake of tracer, 3'-deoxy-3'-(18)F-fluorothymidine (FLT) PET could detect cervical lymph node metastases as well as 2-deoxy-2-(18)F-fluoro-d-glucose (FDG) PET., Objective: The diagnostic efficacy of FLT PET was compared with that of FDG PET regarding nodal staging of head and neck squamous cell cancers., Methods: Twenty-three patients were examined with FLT PET and FDG PET. PET images were evaluated qualitatively for regions of focally increased metabolism and maximum standardized uptake values (SUV) were calculated for semiquantitative analysis., Results: The mean (± SD) FLT SUV in visualized metastatic lymph nodes was 4.8 ± 2.9 as compared with 6.9 ± 4.9 for FDG SUV (p < 0.001). Significant correlations were found between the area of metastatic lymph nodes and both FLT SUV (r = 0.8; p < 0.0001) and FDG SUV (r = 0.84; p < 0.0001). The false-positive (over-staged) and false-negative (under-staged) rates for lymph node staging by FLT PET were 4% (1/23) and 17% (4/23), respectively. Those for FDG PET were 9% (2/23) and 13% (3/23). All metastatic lymph nodes measuring more than 9 mm in short-axis diameter were correctly detected by FLT PET. However, both FLT and FDG PET had low sensitivity for detecting the lymph node metastases ≤ 9 mm in short-axis diameter and tumor deposits < 5 mm.

Objectives: To explore the possible association between the risk of coronary artery disease and head or neck cancer based on some possible shared risk factors and/or treatment-related complications., Design and Setting: A population-based retrospective cohort study., Participants: All new 729 patients with head and neck cancer diagnosed between 2000 and 2003 were followed up till 2009, and the risk of subsequent coronary artery disease was calculated. For each patient, the risk was calculated in 4 age-and sex-matched population controls. Matching was not possible for factors including socio-economic group and smoking., Main Outcome Measures: Cox's proportional hazard regression analysis was conducted to estimate the relationship between head or neck cancer and risk of coronary artery disease., Results: For patients with head or neck cancer, the overall risk for developing coronary artery disease was almost the same as that of the control group [adjusted hazard ratio (but without control for some lifestyle factors): 0.95; 95% confidence interval: 0.65-1.35]. Overall, we found no increased risk of coronary artery disease for patients with head or neck cancer when the data were categorised either by treatment methods or by cancer subsites., Conclusions: This population-based study indicated that patients with head or neck cancer were at no higher risk of developing coronary artery disease than was the general population over a 6- to 9-year period; however, we cannot exclude the risk over a longer period of time., (© 2012 Blackwell Publishing Ltd.)

This article discusses how quality-of-life assessment in patients with head and neck cancer might be weighed against survival and how such assessment might be applied in clinical practice. While survival is understandably considered to be the outcome of primary interest, there are several clinical scenarios in which quality of life can be considered as a primary outcome. Quality-adjusted survival is also an important consideration and needs to be incorporated into the results of treatment. However, quality-of-life assessment has hitherto been virtually only a research tool and not been incorporated into clinical practice. Nowadays, speech pathologists and dietitians are integral to the multidisciplinary team that treats patients with head and neck cancer. The main point of this article is to provide a rationale for the proposition that the health psychologist--who is best able to understand and manage the psychosocial issues--should also be included as one of the team.

Conclusion: Transforming growth factor β1 gene (TGFβ1) genotype is a potential p16 independent prognostic factor predicting response to chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC)., Objectives: Expression of p16 and epidermal growth factor receptor (EGFR) has been reported to be associated with survival in HNSCC. We have previously reported that genetic polymorphism of TGFβ1 is linked with survival in HNSCC patients who have undergone chemoradiotherapy. We evaluate here whether TGFB1 genotype can serve as a prognostic factor independent of tumor p16 and EGFR expression., Methods: Expression of p16 and EGFR was studied by immunohistochemistry in tumors from 130 HNSCC patients. Peripheral blood DNA was used to genotype 95 patients for single nucleotide polymorphism rs1800470 within the TGFβ1 gene. The minimum follow-up time was 31 months., Results: p16 overexpression was associated with an improved disease-free survival (hazard ratio (HR) = 0.39, 95% CI 0.19-0.78), whereas no evident association was observed between EGFR expression and disease-free survival (HR = 0.90, 95% CI 0.68-1.19). Among the 37 patients who had received chemoradiotherapy, TGFβ1 genotype was associated with disease-free (HR = 0.44, 95% CI 0.19-1.02) and overall survival (HR = 0.31, 95% CI 0.12-0.80) independent of tumor p16 expression.

Background: The diagnosis of extranodal natural killer (NK)/T-cell lymphoma (NK/T-cell lymphoma) is often difficult and any delay in its diagnosis leads to a worsened prognosis. We analysed the factors that make the diagnosis of this type of tumour difficult., Methodology/principal: We retrospectively reviewed the medical records of 20 patients with NK/T-cell lymphoma treated in our department, and assessed the clinical features and laboratory findings of the cases. Moreover, we classified factors related to delays in diagnosing NK/T cell lymphoma as follows: (1) insufficient specimen size, (2) massive necrosis, (3) large number of inflammatory cells, and (4) poor atypia. We selected cases requiring two or more biopsies for correct diagnosis and checked which factors were the main cause of misdiagnosis., Results: The average period required for a correct diagnosis was 12.8 months. The most frequent factor leading to diagnostic delay was inflammatory cell infiltration. Massive necrosis and poor atypia were also important factors in diagnostic delay., Conclusions: In cases with necrotic lesions of the nose or pharynx, the possibility of NK/T cell lymphoma should be explored and samples, of as large a size as possible, should be obtained together with EBER-ISH for pathological examination. Repeat biopsies should also be performed for diagnosis.

Purpose: In this work, the treatment tolerance of elderly patients (≥70 years) undergoing intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) and chemotherapy for locally advanced head and neck cancer was assessed., Patients and Methods: A retrospective review of 112 patients undergoing concurrent chemoradiation for locally advanced head and neck cancer was performed. Treatment toxicity, protocol violations, long-term complications, and survival were compared between 85 younger patients (< 70 years) and 27 older patients (≥ 70 years)., Results: Grade 3-4 treatment toxicity was observed in 88.2% and 88.8% for younger and older patients, respectively. Mean weight loss and treatment break were 5.9 and 3.9 kg (p = 0.03) and 7.3 and 7.8 days (p = 0.8) for younger and older patients, respectively. Seven patients (8.2%) did not complete treatment in the younger group compared to 1 patient (3.7%) in the older group (p = 0.6). No significant differences in protocol violations and survival were found between the two groups., Conclusion: Compared to younger patients, elderly patients with locally advanced head and neck cancer tolerated chemoradiation with IMRT and IGRT well, and should not be denied curative treatment based solely on age.

Eustachian tube (ET) primary tumors and tumor-like lesions are rare diseases presenting with common ear, nose and throat symptoms. Pathology can range from developmental anomalies to high malignant neoplasms. Hence this review aimed at suggesting a classification and outline relevant aspects of ET primary tumors and tumor-like lesions, describing clinical findings, diagnostic management and therapeutic approaches. MEDLINE, CINAHL, OVIDSP, HIGHWIRE, and GOOGLE databases were searched from inception to July 2011 for relevant studies. Further papers were identified by examining the reference lists of all included. Sixty-five papers met the inclusion criteria, enclosing 78 cases. Case reports are increasing in the past few years. Benign lesions and tumor-like lesions of ET have been reported. Moreover, melanomas, carcinomas, and sarcomas can affect the ET as a primary site.

Smoking is the main causative factor for development of head and neck and lung cancer. In addition, other malignancies such as bladder, stomach, colorectal, kidney and pancreatic cancer have a causative relation with smoking. Continued smoking after having been diagnosed with cancer has many negative consequences: effectiveness of radiotherapy is diminished, survival time is shortened and risks of recurrence, second primary malignancies and treatment complications are increased. In view of the significant health consequences of continued smoking, therefore, additional support for patients to stop smoking seems a logical extension of the present treatment protocols for smoking-related cancers. For prospectively examining the effect of nursing-delivered smoking cessation programme for patients with head and neck or lung cancer, 145 patients with head and neck or lung cancer enrolled into this programme over a 2-year period. Information on smoking behaviour, using a structured, programme specific questionnaire, was collected at baseline, and after 6 and 12 months. At 6 months, 58 patients (40%) had stopped smoking and at 12 months, 48 patients (33%) still had refrained from smoking. There were no differences in smoking cessation results between patients with head and neck and lung cancer. The only significant factor predicting success was whether the patient had made earlier attempts to quit smoking. A nurse-managed smoking cessation programme for patients with head and neck or lung cancer shows favourable long-term success rates. It seems logical, therefore, to integrate such a programme in treatment protocols for smoking-related cancers.