Addition of chemotherapy to hyperfractionated radiotherapy in advanced head and neck cancer-a meta-analysis.

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.

A clinicopathological study of upper aerodigestive tract cancers.

BACKGROUND: The upper aerodigestive tract (UAT) includes the nose and paranasal sinuses, oral cavity, pharynx, larynx, and salivary glands. Cancers of the UAT constitute approximately 4% of all malignancies. In this study, the varied nature of the UAT cancers was studied to find out their incidence, etiology, and clinicopathological correlations. MATERIALS AND METHODS: This prospective, observational, and clinicopathological study was conducted on 100 patients who were presented at outdoor in the Department of ENT, Government Medical College/Rajindra Hospital, Patiala, Punjab, India, from October 2016 to October 2018. Proven cases of UAT cancers were taken up and reviewed to gather data on multiple clinicopathological variables, such as age, sex, predisposing factors, and site of pathology. Histopathological differentiation was noted after conducting a biopsy. RESULTS: Most patients of UAT cancers were in the age group of 40-70 years. Maximum incidence was among males (82%) compared to females (28%). The most common predisposing factor was alcohol + smoking (28%), followed by alcohol + chewing tobacco (25%). The most common symptom in the oral cavity was ulcer and odynophagia (38%) each. In oropharyngeal cancers, dysphagia (92%) was the most common symptom. In laryngeal cancers, dyspnea (68%) and hoarseness of voice (32%) were the most common. The most common site involved in UAT cancers was the oral cavity (31%), followed by oropharynx (28%), larynx (22%), hypopharynx (7%), and salivary gland (5%). The most common histopathological type was squamous cell carcinoma (SCC) (90%). Most of the ulceroproliferative and exophytic growth was moderately differentiated SCC on histopathology. CONCLUSION: Studies are essential for education and awareness aimed at reducing exposure to habit-forming substances.

[Systemic treatments of metastatic or locally recurrent adenoid cystic carcinoma of the head and neck, a systematic review]. / Traitements systémiques du carcinome adénoïde kystique de la sphère ORL localement avancé ou métastatique, une revue systématique.

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.

The safety and benefit of using oxidized regenerated cellulose to position free flap pedicle in head and neck reconstruction.

BACKGROUND: Oxidized regenerated cellulose (ORC; Surgicel®; Ethicon, Neuchâtel, Switzerland) is an absorbable hemostatic agent used for hemostasis in operation, although some surgeons use it to position free flap pedicles. The increasing risk of vessel compromise is a huge concern. However, no scientific data to date demonstrate the safety and benefit of using ORC in microvascular surgery. In the present study, we compared the outcome of microvascular head and neck reconstruction with and without pedicle placement using ORC. MATERIALS AND METHODS: From January 2015 to December 2017, we reviewed patients undergoing microvascular surgery with free fibular osteocutaneous flap in our hospital. The patients were divided into the ORC group and non-ORC group and their baseline characteristics and outcomes were compared. RESULTS: In total, there were 27 patients in the ORC group and 67 in the non-ORC group. The non-ORC group had significantly higher cigarette consumption (70.4% vs. 89.6%; p = .022). The outcome of the ORC group was better regarding arterial thrombosis (0% vs. 3%), flap failure (0% vs. 4.5%), hematoma (7.4% vs. 10.4%), and wound complications (25.9% vs. 44.8%). The ORC group had a worse result than the non-ORC group for vein thrombosis (7.4% vs. 4.5%) and duration of hospitalization (24.111 days vs. 23.627 days). However, none of above results was significant. CONCLUSIONS: Though this study was underpowered to detect the differences, the results showed a trend toward better outcomes of flaps and wounds in the ORC group. It seems that using ORC in this field is safe and beneficial.

Predicting survival and local control after radiochemotherapy in locally advanced head and neck cancer by means of computed tomography based radiomics.

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.

Association between operation- and operator-related factors and surgical complications among patients undergoing free-flap reconstruction for head and neck cancers: A propensity score-matched study of 1,865 free-flap reconstructions.

OBJECTIVE: Efforts have been devoted to clarify the possible factors related to postoperative complications in free-flap reconstruction. While patient-related factors have been widely discussed, studies regarding the operation/operator-related factors are rather limited in the literature. This study was designed to investigate the relationship between operation/operator-related factors and the surgical complications in free-flap reconstruction following head and neck cancer resection. METHODS: Data of 1,841 patients with a total of 1,865 free-flap reconstructions (24 double free-flap reconstructions) between March 2008 and February 2017 were retrieved from the registered microsurgery database of the hospital. The association of operation/operator-related factors (including flap length and length-width ratio, flap types, use of vein graft, opposite side microanastomosis, number of microanastomoses, operators, operator experience, and operation time) with surgical complications was assessed by 1:1 propensity score-matched study groups. RESULTS: After propensity score matching of the patient-related factors, the rate of vein grafting was significantly higher (0.6% vs. 2.2%, p = .038) and the operation time was longer (7.0 [5.8-8.5] vs. 7.4 [6.1-8.8] hr, p = .006) in the complication group. In addition, flap length and length-width ratio, flap types, opposite side microanastomosis, number of microanastomoses, operators, and operator experience were not associated with surgical complications. CONCLUSIONS: In a hospital that consisted of surgeons with high-volume or very-high-volume experience, the operators or operation experience were not significantly associated with the surgical complications. Only a longer operation time was associated with surgical complications in the patients who underwent free-flap reconstruction for head and neck cancer.

Is there a patient population with squamous cell carcinoma of the head and neck region who might benefit from de-intensification of postoperative radiotherapy? : A monocentric retrospective analysis of a previously defined low-risk patient population treated with standard-of-care radiotherapy.

PURPOSE: The aim of this retrospective study was to evaluate the clinical outcome of a previously defined low-risk patient population with completely resected (R0) squamous cell carcinoma of the oral cavity, oropharynx, larynx (pT1-3, pN0-pN2b), hypopharynx (pT1-2, pN0-pN1), and the indication for postoperative radio(chemo)therapy. PATIENTS AND METHODS: According to predefined criteria, 99 patients with head and neck squamous cell carcinoma (SCC) who were treated at our institution from January 1, 2005 to December 31, 2014, were available for analysis. The Kaplan-Meier method was used for calculating survival and incidence rates. For univariate comparative analysis, the log-rank test was used for analyzing prognostic clinicopathologic parameters. RESULTS: Median follow-up was 67 months. Cumulative overall (OS) and disease-free survival (DFS) were 97.9%/94.7%/88.0% and 96.9%/92.6%/84.7% after 1, 2, and 5 years, respectively. Cumulative incidence of loco-regional recurrence (LRR), distant metastases (DM), and second cancer (SC) were 1.0%/1.0%/4.9%, 0.0%/3.4%/5.8%, and 2.1%/4.2%/13.1%, respectively. In univariate comparative analysis, location of the primary tumor in the oropharynx was a significant predictor for increased OS (p = 0.043) and DFS (p = 0.048). CONCLUSION: Considering the low disease relapse rates and high rates of therapy-induced late side effects, as well as the increased risk of developing SC, a prospective multicentric trial investigating de-escalation of radiotherapy in this clearly defined low-risk patient population was started and is still recruiting patients (DIREKHT-Trial, NCT02528955).

Unilateral cochlea sparing in locoregionally advanced head and neck cancer: a planning study.

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.

Imaging features of sinonasal tumors on positron emission tomography and magnetic resonance imaging including diffusion weighted imaging: A pictorial review.

INTRODUCTION: Sinonasal inflammatory conditions account for a major component of head and neck pathologies, whereas neoplasms involving the sinonasal region make up only 2-3% of all head and neck lesions. The symptoms of sinonasal tumors are nonspecific; imaging plays a critical role in distinguishing benign and malignant disease and may illustrate characteristic radiological features of specific sinonasal tumors. OBJECTIVE: Aim was to determine the utilization of multimodality imaging, specifically the metabolic information provided by 18-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) and diffusivity characteristics seen with diffusion weighted images (DWI) of magnetic resonance imaging (MRI), in a wide range of benign and malignant sinonasal tumors drawn from over 200 sinonasal lesions from our institution and supplemented by the literature. CONCLUSION: In this pictorial essay, we have reviewed common imaging characteristics of frequently encountered in sinonasal tumors and divided them into benign and malignant categories to facilitate creation of focused differential diagnoses.

Polyfunctionality of CD4+ T lymphocytes is increased after chemoradiotherapy of head and neck squamous cell carcinoma.

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.

Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup.

PURPOSE: The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [18F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup. METHODS: Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI). Primary tumours were manually segmented and quantitative imaging parameters were extracted. PET standardized uptake values (SUV) and DWI apparent diffusion coefficients (ADC) were correlated on a voxel-wise level. RESULTS: Images acquired in this specialised radiotherapy planning setup achieved good diagnostic quality. Median tumour volume was 4.9 [1.1-42.1] ml. Mean PET SUV and ADC of the primary tumours were 5 ± 2.5 and 1.2 ± 0.3 10-3 mm2/s, respectively. In voxel-wise correlation between ADC values and corresponding FDG SUV of the tumours, a significant negative correlation was observed (r = -0.31 ± 0.27, p < 0.05). CONCLUSION: Multiparametric voxel-wise characterization of HNSCC is feasible using combined PET/MRI in a radiation planning setup. This technique may provide novel insights into tumour biology with regard to radiation therapy in the future.

Patient positioning in head and neck cancer : Setup variations and safety margins in helical tomotherapy.

OBJECTIVE: To evaluate the interfractional variations of patient positioning during intensity-modulated radiotherapy (IMRT) with helical tomotherapy in head and neck cancer and to calculate the required safety margins (sm) for bony landmarks resulting from the necessary table adjustments. MATERIALS AND METHODS: In all, 15 patients with head and neck cancer were irradiated using the Hi-Art II tomotherapy system between April and September 2016. Before therapy sessions, patient position was frequently checked by megavolt computed tomography (MV-CT). Necessary table adjustments (ta) in the right-left (rl), superior-inferior (si) and anterior-posterior (ap) directions were recorded for four anatomical points: second, fourth and sixth cervical vertebral body (CVB), anterior nasal spine (ANS). Based upon these data sm were calculated for non-image-guided radiotherapy, image-guided radiotherapy (IGRT) and image guidance limited to a shortened area (CVB 2). RESULTS: Based upon planning CT the actual treatment required ta from -0.05 ± 1.31 mm for CVB 2 (ap) up to 2.63 ± 2.39 mm for ANS (rl). Considering the performed ta resulting from image control (MV-CT) we detected remaining ta from -0.10 ± 1.09 mm for CVB 4 (rl) up to 1.97 ± 1.64 mm for ANS (si). After theoretical adjustment of patients position to CVB 2 the resulting ta ranged from -0.11 ± 2.44 mm for CVB6 (ap) to 2.37 ± 2.17 mm for ANS (si). These data imply safety margins: uncorrected patient position: 3.63-9.95 mm, corrected positioning based upon the whole target volume (IGRT): 1.85-6.63 mm, corrected positioning based upon CVB 2 (IGRT): 3.13-6.66 mm. CONCLUSIONS: The calculated safety margins differ between anatomic regions. Repetitive and frequent image control of patient positioning is necessary that, however, possibly may be focussed on a limited region.

Application of flexible endoscopy-based biopsy in the diagnosis of tumour pathologies in otorhinolaryngology. / Aplicación de la biopsia por endoscopia flexible en el diagnóstico de la patología tumoral en otorrinolaringología.

INTRODUCTION AND OBJECTIVES: Interventional endoscopy allows us to act on the pathology of the patient with minimal discomfort, low costs and high efficiency. We assessed the validity of flexible endoscopic biopsies in our hospital, in lesions suspected of malignancy in the rhino-pharyngo-laryngeal space. SUBJECTS AND METHODS: Retrospective study of patients with a pathology suspected of malignancy assessed between 2006-2016 in our centre. We evaluated the effectiveness, the tolerance and the number of complications. We calculated the cost reduction in comparison with direct laryngoscopy in the operating room. We compared our sample with others of similar characteristics described in the literature. RESULTS: Thirty patients were studied with a flexible endoscopic biopsy during that period. Nineteen patients obtained positive results which allowed them to start treatment for their pathology. Seven cases had no evidence of malignancy and required another biopsy under general anaesthesia, which confirmed the carcinoma diagnosis. Two samples ruled out malignancy which was confirmed by laryngeal microsurgery. One case showed inflammation and the lesion was cured after antibiotherapy. It was impossible to collect the sample in one case. Thus, we obtained sensitivity levels of 73% with a specificity of 100%. There were no complications. The cost reduction in our sample was above 80%. CONCLUSIONS: Flexible endoscopic biopsy has advantages over direct laryngoscopy that are relevant in the diagnosis of oncological pathology in otorhinolaryngology.

Haemorrhage following transoral robotic surgery.

BACKGROUND: To report our experience of postoperative haemorrhage in patients following transoral robotic surgery (TORS). METHODS: Data were collected on patients having TORS. Postoperative haemorrhage within 30 days was graded using the Mayo Clinic grading system. RESULTS: Transoral robotic surgery operations were performed on 122 patients. There were 23 bleeding events classified as minor to severe following 19 operations (16%). Haemorrhage requiring a return to the operating room occurred after 7 operations (6%). The odds of an emergent haemorrhage were 5.19 times greater in patients who had a staged neck dissection after TORS (P = .05). The odds of a postoperative bleeding event were 2.6 times greater in patients receiving a larger resection (P = .107). There were no haemorrhage events in the 36 patients who received a synchronous neck dissection with transcervical ligation of the external carotid artery. CONCLUSIONS: Surgical intervention for TORS haemorrhage occurred in 6% patients. No haemorrhage occurred in patients who had ligation of the external carotid artery.

Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region.

PURPOSE: Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y­box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region. MATERIALS AND METHODS: DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively. RESULTS: DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels. CONCLUSION: Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

[Extracranial schwannomas of the Head and Neck: Clinical -approach based on 20 cases]. / Extrakranielle Schwannome im Kopf-Hals-Bereich: Klinische Implikationen anhand von 20 Fällen.

Background Schwannomas are rare benign tumors originating from the perineural cells forming the myelin layer in the peripheral nervous system (PNS). While well established therapeutic concepts exist for intracranial schwannomas, there is a lack of consistent clinical standards for extracranial schwannomas. Method This retrospective study describes the clinical pathway of 20 patients with histologically proven extracranial schwannomas of the head and neck. The diagnostic and therapeutic strategies for schwannomas are discussed with special emphasis on localization and functional outcome. Results Extracranial schwannomas of the head and neck region mostly originated from the facial nerve (n = 4), vagal nerve (n = 4) or sympathetic chain (n = 3). Most common symptoms were swelling (n = 12) and pain (n = 3). Preoperative imaging included MRI (n = 13), ultrasound (n = 12) and CT (n = 3). Surgical intervention was performed in 18 cases (n = 14 complete extirpation, n = 3 partial extirpation, n = 1 unknown). Regarding completely extirpated schwannomas of motor nerves (n = 10) severing the nerve of origin was more often required in patients with a preexisting functional deficit (3 out of 4 = 75 %) than in patients without preexisting deficits (2 out of 6 = 33 %). Conclusion Representing rare tumors of the head and neck region mostly originating from the facial nerve, sympathetic chain or caudal cranial nerves extracranial schwannomas require a systematic diagnostic and therapeutic approach. Postoperative functional deficits after complete extirpation must especially be anticipated in patients with a preexisting functional deficit.

[Immunotherapy Against Head and Neck Cancer Stem Cells]. / Immuntherapie gegen Tumorstammzellen bei Plattenepithelkarzinomen im Kopf-Hals-Bereich.

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.

Hyperfractionated accelerated radiation therapy plus cetuximab plus cisplatin chemotherapy in locally advanced inoperable squamous cell carcinoma of the head and neck : Final 5­year results of a phase II study.

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/m2) and then with a weekly dosage of 250 mg/m2 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/m2) was administered weekly (days 1, 8, 15, 22, 29 and 36). The primary objective of the phase II study was to determine the 2­year 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 5­year overall survival rates were 64 and 41%, the 2­ and 5­year PFS rates were 45 and 32%, and the 2­ and 5­year 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.