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Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

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.

Introduction: Adenoid Cystic Carcinoma is a rare tumor of the head and neck sphere. The purpose of this review is a state of the art of systemic treatments (chemotherapies, targeted therapies, immunotherapies) for locally recurrent or metastatic disease., Material and Methods: Our inclusion criteria included head and neck adult patient, metastatic or locally advanced, treated by a systemic therapy, and with at least 10 or more patients., Results: Forty articles have been selected in this review. The objective response rate under chemotherapy was predominantly<10% (0-70%) with objective responses in monotherapy with cisplatin, mitoxantrone, vinorelbine and eribuline, and with cisplatin-vinorelbine combination. EGFR inhibitors provided 40% objective responses only in combination. Inhibitors of VEGF and histone deacetylase have allowed disease stabilization in progressive patients, with about 10% of objective response. Inhibitors of c-KIT monotherapy yield objective response rates of<5%. Direct inhibitors of the PI3K/AKT/mTOR pathway display 0% objective response rate., Conclusion: The best objective response rates were obtained with cisplatin-vinorelbine combination. Many targetable molecular abnormalities have been identified and studies have shown prolonged stabilization with EGFR, VEGF and HDAC inhibitors. Multi-disciplinary collaborative consultation (MCC) meetings such as French network of experts in rare head and neck tumors (REFCOR) or Molecular MCC should be proposed and may allow referral to centers proposing specific therapeutic trials., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

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.

Purpose: Alternative and complementary medicine is defined as any substance or technique of non-allopathic medicine used to improve health and quality of life. The purpose of this prospective observational study was to evaluate the use of alternative and complementary medicine during radiotherapy., Material and Methods: A questionnaire was given the last week of treatment to all patients treated for breast cancer, prostate cancer or head and neck cancer in our centre in 2016., Results: In 2016, 132 patients were included. Fifty-seven patients (43%) used alternative and complementary medicine during radiotherapy, more women (61%) than men (35%) (P=0.005). The use of alternative and complementary medicine varied according to locations: 44% of head and neck cancers, 57% of breast cancers and 24% of prostate cancers, but sex was the confounding factor. If alternative and complementary medicine was used before radiotherapy, 82% of patients used it during treatment, compared to 30% if they were naive (P<10 -7 ). Healing touch (68%), homeopathy (26%) and magnetisers (21%) were the most used alternative and complementary medicines. Sixty-one percent of patients used alternative and complementary medicine to reduce skin and mucosal side effects of treatments, 28% to improve well-being, and 9% to treat cancer. Seventy-two percent of all patients would advise their loved one to use an alternative and complementary medicine and 87% would like information about them in the hospital., Conclusion: Alternative and complementary medicines are used more by women, and by patients who used them before radiotherapy. The desired effects are mainly to reduce the side effects of the treatments. More than 80% of patients, whether or not they use alternative and complementary medicine, demand medical information., (Copyright © 2018. Published by Elsevier Masson SAS.)

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.)

The aim of psychooncological interventions are to facilitate coping with the disease, to improve the psychological well-being and quality of life of the cancer patients as well as the strengthening of personal and social resources.Apart from general strain going along with oncological diseases and its treatment, patients with head and neck cancer often also suffer from impairment of the most basic human functions (speech, swallowing, food intake).Patients with head and neck cancer are one of the most distressed and burdened groups of cancer patients.Psychooncological interventions apply proven psychological and psychotherapeutic methods and techniques.Psychooncological treatment is based on the close interdisciplinary cooperation of different professional groups., (© Georg Thieme Verlag KG Stuttgart · New York.)

Immunotherapy is on the roll. After revolutionary effects in melanoma, immunotherapy is invading other locations. If current treatments, chemotherapies or targeted therapies block one pathway, immunotherapy should be understood as the activation of a whole system. Indeed, oncogenesis process is defined as an escape of the immune system and the stimulation of this system can block the carcinogenic process. The aim of the present review is to describe the place of immunotherapy in the treatment of solid cancers., (Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Immunotherapy against head and neck cancer stem cells Immunologic therapies like antibodies in solid tumors like squamous cell cancer of the head and neck are administered either alone or in combination with radiation and chemotherapy. Despite some respectable successes, the effect of this therapy reaches its limits due the ability of the tumor to escape the immune system. Cancer stem cells seem to play an important role in this process due to their intrinsic resistance to conventional therapy and the ability to regenerate tumor heterogeneity. This way they substantially contribute to the formation of recurrences and metastases. Therefore, future immunotherapies should target specifically this subpopulation, possibly in combination with other therapeutic modalities. In this review the immunologic features of cancer stem cells and their potential as target for immunotherapies is summarized., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

Objective: The diagnosis of cancer in pregnancy is rare, but might become more relevant even for head and neck cancer patients due to a shift of age of primipara towards the last third of reproductive years. Unsureness exists about the risk and benefit of diagnostic and therapeutic cancer modalities for the unborn and established recommendations are still missing. But, according to recent data, even multimodal therapeutic approaches (e. g. surgery, radiation, chemotherapy) seem possible in face of pregnancy and should be traded against the risk of prematurity. Material and Methods: Our findings are discussed on the basis of a case report of a pregnant woman with advanced carcinoma of the outer ear canal and therapy options are formulated. Results: Sufficient performed diagnostic modalities do not reach imperilling uterus dosages. A growing number of case reports und studies did not detect any developmental disadvantage of children of prenatal exposed mothers by radiation or chemotherapy, whereas long-term impairments of premature infants are proven. Conclusion: In cancer in pregnancy, an immediate start of well-established therapy modalities like surgery and/or cisplatin-based chemoradiation seems to be possible without unjustifiable risks for the unborn., (© Georg Thieme Verlag KG Stuttgart · New York.)

Tumors of the head and neck form a heterogeneous group of benign and malignant neoplasms with significant differences in biological behavior and therapeutic strategies. Squamous cell carcinomas (SCC) of the larynx, pharynx and oral cavity represent the most frequent and, thus, clinically most important malignant neoplasms in this anatomical region. Similar to other neoplasms, grading of head and neck malignancies is based on evaluation of the tumor histology usually including both architectural and cytological features; however, the current consensus grading for head and neck SCC is of limited prognostic and therapeutic value and the reproducibility is low. Therefore, novel grading criteria have been proposed that are based on additional parameters, such as the type of tumor growth pattern at the invasive front (so-called tumor budding). These novel algorithms, however, have not yet been officially endorsed into guidelines. Salivary gland (SG) neoplasms, although less frequent, constitute a second important pathologically and clinically complex group of tumors at this location. In contrast to SCC, grading of these tumors is of high clinical importance. Based on the large variety of carcinoma entities of the SG, both entity-specific (e. g. mucoepidermoid carcinoma) algorithms but also algorithms, which are solely based on the recognition of a specific carcinoma variant with subsequent automatic assignment of the tumor grade (e. g. acinic cell carcinoma and salivary duct carcinoma) are in use. In the sinonasal tract, grading is important for non-intestinal type adenocarcinoma and esthesioneuroblastoma. In this article the most important grading schemes and criteria for head and neck malignancies are presented and their prognostic and therapeutic implications are discussed.

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.

Introduction: Malignant and benign cells differ according to their elasticity. An atomic force microscope is a useful tool for measuring these mechanical cell properties. If cells of different dignity show different resonance behavior, due to their different elasticity, a selective ablation of specific tissue types by ultrasound would be possible. The goal is a highly selective ablation of tumor tissue without damaging healthy tissue., Materials and Methods: We performed elasticity measurements of tumor cells (UD-01 cell line) with an atomic force microscope. In a further step, an ultrasound applicator has been positioned and the morphological changes of the cells during the treatment were documented., Results: Different elasticities on the squamous cells were measured, depending on the location. Below a defined maximum amplitude the morphological cell changes were caused solely by ultrasonic excitation., Summary: The atomic force microscope is suitable for the determination of the individual cell elasticity. The data collected could be the basis for treatment modalities that lead to a very selective damage for malignant cells., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

Introduction: The follow-up for head and neck cancer (HNC) focussed on therapy control. Accessory long term functionality is important. Impairment of function is observed, but a comparable documentation is not established. Additional we frequently see psychooncological comorbidities, what complicates the assessment. This was the reason why Tschiesner et al. developed on the base of the "ICF Core set for head and neck cancer" a guideline for the Assessment of Function in HNC. In consequence of good results in other tumour entities we developed an electronic version (OncoFunction)., Methods: In a proof of concept study all patients of our follow up consultation from 07/13 to 03/14 were included. OncoFunction was given to patients in a digital form using tablet computers. The results were visible to the physician in a concentrated form before consultation and were supplemented by a physician questionnaire. Furthermore we evaluated the usability in 202 patients., Results: We had 682 patient contacts. 530 patient contacts (77, 7%) used the questionnaire. The physician questionnaire was answered in 470 times. Finally there are from 69.8% of the patient contacts full datasets available. Between users and non-users of the questionnaire we see no difference., Conclusion: The use of a computer-based screening and feedback system (OncoFunction) in clinical use is feasible and excellent assessed by patients. The patient data are visible in a compact form for the physician and problems can clear addressed to the patient. One more benefit is the standardized follow up documentation and the use of comparable data in research., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

Primary mucosal malignant melanoma of the head and neck is a rare tumor entity with poor clinical outcome. Its growth pattern is characterized by an infiltrative and local destructive behavior. So far no risk factors could be identified. There are practically no early symptoms of the disease, as intermitting nose bleeding or nasal obstruction typically occur in advanced stage. The standard of care remains radical tumor resection with adjuvant radiation in cases of close margin resection. Other therapeutic options like the use of interferon, antibodies or conventional chemotherapeutics have not demonstrated significant clinical benefit so far. Current efforts to investigate the biological and genomic characteristics of these tumors have been constrained by its low incidence. In order to better characterize this rare tumor entity and to establish effective novel targeted therapies it will be necessary to establish an interdisciplinary and multicentric task force., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.

Circulating tumor cells are defined as tumor cells which are circulating in the peripheral blood of the cancer patient. While several large studies have investigated the role of circulating tumor cells in other solid tumors, the importance of these tumor cells in patients with head and neck cancer was turned into the focus not until the recent years. In other solid tumor the presence of circulating tumor cells often seems to be a negative prognostic marker and seems to be a marker for therapy response. The present article wants to give an overview about the knowledge on circulating tumor cells and their clinical relevance in head and neck cancer. The methodology to detect circulating tumor cells will be critically reflected. The future potential of the detection of circulating tumor cells in head and neck cancer patients will be discussed., (© Georg Thieme Verlag KG Stuttgart · New York.)

Meta-analyses are considered as an important pillar of evidence-based medicine. The aim of this review is to describe the main principles of a meta-analysis and to use examples of head and neck oncology to demonstrate their clinical impact and methodological interest. The major role of individual patient data is outlined, as well as the superiority of individual patient data over meta-analyses based on published summary data. The major clinical breakthrough of head and neck meta-analyses are summarized, regarding concomitant chemotherapy, altered fractionated chemotherapy, new regimens of induction chemotherapy or the use of radioprotectants. Recent methodological developments are described, including network meta-analyses, the validation of surrogate markers. Lastly, the future of meta-analyses is discussed in the context of personalized medicine., (Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

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.

Objective: Describe the implementation and preliminary results of the “Experimental Program Personalized care” in patients with Head and Neck cancer., Materials and Methods: After being selected a graduate nurse status, called coordination, participated in the development of forms of detection needs and concerns of patients, in collaboration with various health professionals., Results: Between January 2011 and December 2012, 200 new patients with head and neck cancer were included: 62% with advanced cancer and 38% of early stage. No patient refused to participate in this experiment. At least one consultation with a psychiatrist was necessary for 82% of patients with advanced cancer. Social problems were the second axis of the needs of patients., Conclusion: By identifying the needs of patients and organizing their support, this evaluation optimizes not only the therapeutic care for the patient but also the management of human resources within the team.

The adenoid cystic carcinoma (ACC) is a neurotropic salivary gland tumor with a high blood-borne metastasis tendency. The treatment of choice for localized disease consists of radical surgical resection and, depending on resection status, adjuvant radiotherapy. Due to the high recurrence rate with limited local therapeutic options and frequent occurrence of distant metastases, one is confronted inevitably with the search for an adequate systemic therapy. ACC shows little response to a variety of chemotherapeutic agents, partial or complete remissions are extremely rare. Beside classical chemotherapies, immunotherapeutics and targeted therapies with more favorable side effect profiles were tested in trials, but due to the small number of patients, a definitive statement on the effectiveness can be hardly made. This results in the need for prospective multicenter studies that allow clear recommendations for systemic therapy of the tumor. The present paper gives an overview of the sub-cellular and genetic characteristics of ACC, which represent possible targets for systemic therapies and have partly already been included in running clinical trials., (© Georg Thieme Verlag KG Stuttgart · New York.)