Management of patients with seasonal allergic rhinitis: Diagnostic consideration of sensitization to non-frequent pollen allergens.

BACKGROUND: Diagnosis of pollen allergies is mainly based on test allergens for skin prick testing. In the minimum battery of test inhalant allergens recommended by the Global Allergy and Asthma European Network 10 pollen allergens are included. Complementary other pollen allergens may need to be considered; however, respective awareness may not always be granted. Furthermore, at least in Germany, the situation may be even more complicated by the fact that test allergens need regulatory approval. A decline in commercially available test allergens may result in a diagnostic gap regarding patients with non-frequent allergies. How many patients with non-frequent pollen allergies would be affected by this gap? The data presented here partly answer this question. METHODS: The study consisted of a descriptive and an analytical part. In the descriptive part, sensitization to frequent pollen allergens (alder, hazel, birch, sweet grasses; according to the German Therapy Allergen Ordinance) and to respective non-frequent pollen allergens (cypress, Japanese cedar, ash, plane tree, olive, Bermuda grass, wall pellitory, plantain, goosefoot, mugwort, ragweed, and saltwort) was measured in adult patients with physician-diagnosed allergic rhinitis from two German federal states, namely North-Rhine Westphalia (n = 360) and Bavaria (n = 339), using skin prick testing and/or ISAC technology. Furthermore, respective regional pollen data were assessed. In the analytical part, sensitization data were correlated with each other and with anamnestic data on symptom periods. RESULTS: Sensitization to frequent pollen allergens ranged from 45% (sIgE to Aln g 1/Alder, NRW) to 72% (prick test reactivity to birch, NRW). Sensitization to non-frequent pollen allergens ranged from 0% (sIgE to Amb a 1/ragweed, NRW) to 41% (prick test reactivity to olive, Bavaria). Sensitization data partly correlated with each other and in connection with symptom periods showed a partly similar seasonal pattern as pollen data. CONCLUSIONS: Sensitization to non-frequent pollen allergens have to be considered when examining patients with respective seasonal symptoms, and test (and respective therapy) allergens for non-frequent pollen allergies need to be available. Further prerequisites for adequate patient management would be a nationwide pollen monitoring system giving continuous pollen data and a systematic sensitization monitoring at patient level.

Mono-institutional retrospective cohort analysis of the insurance status dependent access to ENT-professionals and survival in head and neck squamous cell carcinoma.

BACKGROUND: To access the influence of insurance status on time of diagnosis, quality of treatment and survival in head and neck squamous cell carcinoma (HNSCC). METHODS: This mono-institutional retrospective cohort analysis included all HNSCC patients (n = 1,054) treated between 2001 and 2011, and subdivided the cohort according to the insurance status. Differences between the groups were analyzed using the Chi square and the unpaired student's t-test. Survival rates were calculated by Kaplan-Meier and Cox regression for forward selection. RESULTS: Nine hundred twenty-five patients showed general, 129 private insurance. The 2 groups were equal regarding age, gender, tumor localization, therapy, and N/M/G/R-status. The T-status differed significantly between the groups showing more advanced tumors in patients with general insurance (p = 0.002). While recurrence-free survival was comparable in both groups, overall survival was significantly better in private patients (p = 0.009). The time frame between first symptom and diagnosis was equal in both groups. CONCLUSIONS: The time frame between subjective percipience of first symptom and final therapy did not differ between the groups. In our cohort, access to otorhinolaryngological specialists is favorable in both, patients with general and private insurance. Recurrence-free survival was comparable in both groups, indicating successful HNSCC treatment both groups. However, overall survival was significantly better in patients with private insurance suggesting other socioeconomic factors influencing survival.

MRI- and CT-determined changes of dysphagia / aspiration-related structures (DARS) during and after radiotherapy.

PURPOSE: The concept of dysphagia/aspiration-related structures (DARS) was developed against the background of severe late side effects of radiotherapy (RT) for head and neck cancer (HNC). DARS can be delineated on CT scans, but with a better morphological discrimination on magnetic resonance imaging (MRI). Swallowing function was analyzed by use of patient charts and prospective investigations and questionnaires. METHOD: Seventeen HNC patients treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy between 5/2012 - 8/2015 were included. Planning CT (computed tomography) scans and MRIs (magnetic resonance imaging) prior, during 40 Gray (Gy) radiotherapy and posttreatment were available and co-registered to delineate DARS. The RT dose of each DARS was calculated. Five patients were investigated posttreatment for swallowing function and assessed by means of various questionnaires for quality of life (QoL), swallowing, and voice function. RESULTS: By retrospective comparison of DARS volume, a significant change in four of eight DARS was detected over time. Three increased and one diminished. The risk of posttreatment dysphagia rose by every 1Gy above the mean dose (D mean) of RT to DARS. 7.5 was the risk factor for dysphagia in the first 6 months, reducing to 4.7 for months 6-12 posttreatment. For all five patients of the prospective part of swallowing investigations, a function disturbance was detected. These results were in contrast to the self-assessment of patients by questionnaires. There was neither a dose dependency of D mean DARS volume changes over time nor of dysphonia and no correlation between volume changes, dysphagia or dysphonia. CONCLUSION: Delineation of DARS on MRI co-registered to planning CT gave the opportunity to differentiate morphology better than by CT alone. Due to the small number of patients with complete MRI scans over time, we failed to detect a dose dependency of DARS and swallowing and voice disorder posttreatment.

"New" inhalant plant allergens.

Specific IgE measurements obtained from patients suffering from respiratory allergy (n = 952) show that, despite similar climatic conditions, there are clear regional differences in pollen sensitization between North Rhine-Westphalia and Bavaria. The data on sensitization levels and pollen concentration was taken from the research and development project Ufoplan 3710 61 228 of the German Environment Agency for North Rhine-Westphalia and Bavaria (2011 - 2014). Most poly-sensitized patients have already shown sensitization, both in the form of cross-reactivity and species-specific sensitization, to "new" pollen allergens, such as Bermuda grass and olive tree. These plants are currently not common in Germany, but may become considerably more widespread due to the increase in average yearly temperatures caused by the global warming. The other "new" aeroallergens discussed here are plants that can be found throughout Germany, such as nettle, cypress, and pine. Their current sensitization levels are higher than 8%; however, their clinical impact appears to be underestimated. For clinical practice it is important to identify when patients' symptoms are typically severe and which regional plants might be responsible for the patients' complaints in this period of time, as this affects further diagnostic strategy. Allergens having an immune effect can then be targeted by specific immunotherapies. The information on complaints of the patients should be regularly recorded in symptom diaries. Recording this information for at least 1 year may allow to discover a correlation between specific types of pollen and allergy symptoms.

Bilateral versus ipsilateral neck dissection in oral and oropharyngeal cancer with contralateral cN0 neck.

OBJECTIVE: Contralateral elective neck dissection (cEND) in oral and oropharyngeal squamous cell cancer (OC/OPC) is still a matter of debate. The current study analyzed the outcome in OC/OPC patients with/without cEND. METHODS: OC/OPC patients (n = 471) were diagnosed with contralateral N0 after CT/MRI-scan combined with neck ultrasound. Clinico-pathological features were analyzed using Chi-square/Fisher exact/Student's t test. Survival rates were calculated using Kaplan-Meier and log-rank test. Prognostic variables were evaluated by Cox regression. Primary/secondary endpoints were overall/recurrence-free survival (OS/RFS). RESULTS: Pre-therapeutic imaging revealed a significantly over-staged N-status (p = 0.01), while occult contra-lateral N + was diagnosed in one patient only (0.4%). OC patients did not show differences in OS/RFS between the groups (ipsi- vs. bi-lateral). There was a strong tendency towards a better OS in OPC patients who underwent ipsi-lateral ND (p = 0.07). Cox-regression demonstrated that only tumor recurrence was associated with a fivefold increased risk of recurrence-associated death (p < 0.0001) that referred to a significant higher recurrence rate at primary tumor site (rT +) and increased distant metastatic outgrowth in OPC who underwent bi-lateral neck dissection (p = 0.03). While RFS of any cause (rT + /rN + /rM +) was significantly better in OPC with ipsi-lateral ND (p < 0.05), RFS of contralateral lymph node recurrence (rN2c) was comparable in both groups. CONCLUSION: END of the contralateral cN0 neck is not correlated by an increased RFS or OS. Standard imaging techniques including CT/MRI scan and neck ultrasound warrant watchful waiting for neck dissection of the contralateral cN0 neck.

Chemoradiation and local recurrence of head and neck squamous cell carcinoma and the risk of carotid artery blowout.

BACKGROUND: Carotid blowout syndrome (CBS) is a rare but life-threatening complication of head and neck squamous cell carcinoma (HNSCC). Chemoradiation (CRT) may make CBS more likely, but so far no longitudinal analysis of different treatment strategies has been conducted. METHODS: In the present study, 1072 patients with HNSCC were divided into groups depending on whether they had experienced CBS. Disease-related data were analyzed using chi-square test, Fisher exact test, and Student's t test. Survival rates were calculated using Kaplan-Meier test, log-rank test, and the Cox regression analysis for forward selection. RESULTS: Thirty-six patients suffering from CBS demonstrated significantly advanced T status (P = .001) and UICC stage (P = .004) when compared with unaltered counterparts. After adjustment for UICC stage, OS was comparable in both groups, whereas the mean recurrence-free survival (RFS) rate was better in unaltered patients (67 vs 24 months; P < .0001). Cox regression for forward selection revealed local recurrence (hazard ratio [HR], 1.9; P < .0001), T status (HR, 1.9; P = .03), and CRT (HR, 2.0; P < .0001) as independent risk factors for mortality related to CBS. CONCLUSION: CBS is a rare event in patients with HNSCC demonstrating reduced OS/RFS. Advanced T status, C/RT, and the recurrence of local tumors increase the risk of CBS-associated death.

Cancer clinical trials - Survey evaluating patient participation and acceptance in a university-based Comprehensive Cancer Center (CCC).

INTRODUCTION: Prospective clinical trials are essential to translate new therapy concepts or rather any scientific development into the medical routine. Besides a sophisticated trial protocol, the success of clinical trials depends on patient recruitment and participation. Patient recruitment remains a challenge and depends on several factors. To get a current picture of the patients' attitude, we conducted the present survey. METHODS: We designed a survey with seven questions, which was given to all oncological patients treated within a timeframe of three months between Mai and July 2017. Participation was voluntary and anonymous. The questionnaire mainly inquires patients' participation in clinical trials in a university-based setting, their attitude towards clinical trials regarding risks and benefits, and their source of information in this context. RESULTS: 771 patients (1:1 male/female) participated with a median age of 61 years (range 18-91 years) with a response rate of 71.5%. Of all, 17.8% (137/771) were participating in a clinical trial. The most mentioned reason was to serve medical progress and cancer research. Out of the patients not currently participating in a trial, 79 (12.7%, 79/623) refusers named the following main reasons: extensive travel time to the clinic, no therapeutic advantage, and too time-consuming. Out of the patients not offered to take part in a trial, 265 (51.0%, 265/520) would participate if offered. Of all patients, 8.3% (64/771) used the clinics' homepage as a source of information, of those 79.7% (51/64) were satisfied with its content. To enhance patient recruitment strategies, we asked how patients wish to be informed about possible trials: More than half (52.0%) of the questioned patients preferred an individual medical consultation with their physician.We further analyzed the trial participation depending on age, gender, unit, and tumor entity. We could show a significant influence of age (p < 0.001) but not for gender (p = 0.724). The trial participation was also significantly associated with the treating unit (p < 0.001) and tumor entity (p = 0.001). CONCLUSION: Patients are willing to participate in clinical trials. Better information strategies need to be implemented. Physicians need to be aware of running trials within their department and must counseling counsel patients effectively to improve recruitment. Trial concepts should keep in mind patients' needs including an adequate number of appointments, positive risk-benefit profiles, and information material.

Therapeutic implications of tumor free margins in head and neck squamous cell carcinoma.

OBJECTIVES: The resection status is one of the most important prognostic factors for patients with head and neck squamous cell carcinoma (HNSCC) concerning overall survival (OS) and recurrence free interval (RFI). To assess whether therapy concepts changed depending on different resection margins and extracapsular extension, OS and RFI data were set into clinical context. METHODS: All HNSCC patients who underwent head and neck surgery with/without adjuvant therapy (n=534) were selected over a ten-year period (2001-2011). Clinical parameters and survival data were collected retrospectively and histopathological analysis of tumor free margins and extracapsular extension were done. RESULTS: Patients with microscopic in-sano resection showed mean OS/RFI of 95/96 months. OS/RFI decreased in microscopic non-in-sano and macroscopic non-in-sano (56/58 and 35/39 months) as well as in unclear resection margins (63/60 months). Patients with extracapsular extension, microscopic non-in-sano resection as well as patients with in-sano resection after follow up resection demonstrated therapy escalation by adjuvant (chemo-) radiation. CONCLUSIONS: Insufficient surgical margins and extracapsular extension are main risks for a reduced overall and recurrence free survival. Although there is no measure to prevent positive extracapsular extension, clear margins at first pass protect patients from adjuvant therapy escalation.

Mammary analogue secretory carcinoma of salivary glands: diagnostic pitfall with distinct immunohistochemical profile and molecular features.

Mammary analogue secretory carcinoma (MASC) is a newly defined entity among salivary gland malignancies which has just been established in the 4th edition of the WHO classification of head and neck tumors. MASC (synonym: secretory carcinoma) are characterized by a specific rearangement of the ETV6 gene locus. Here, we present a series of 3 MASC cases including clinical data with follow-up for up to 26 months. All tumours immunhistochemically displayed strong positivity for cytokeratin 7, and mammaglobin, focal positivity for S100, cytokeratin 5/6 and muc-4. In contrast, immunhistochemical stainings against cytokeratin 14, hormon receptors, Her2/neu, androgen receptor and prostate-specific antigen were consistently negative. FISH analysis showed translocation of the ETV6 gene locus in the majority of tumour cell nuclei. During clinical follow-up, no local relapse or metastasis was detected. As these carcinomas are clinically and radiologically indistinguishable from other salivary gland tumours and as therapeutic approaches and prognosis might differ, we need to be able to diagnose MASC correctly.

Bipolar dissection technique in parotid gland surgery.

BACKGROUND: Parotid gland surgery (PGS) has to manage the balancing act between sufficient radicality and preservation of functional structures. While many studies evaluate post-therapeutic complication due to different extent of surgery, the current study introduces bipolar dissection (BP) being a fast and safe preparation technique. METHODS: Analysis of clinical parameters (age, sex, tumour entity, treatment modalities, facial nerve palsy, bleeding, saliva fistula and Frey's syndrome) of 319 consecutively included patients who underwent extracapsular dissection and superficial/total/radical parotidectomy. Subgroup analysis was done according to the preparation technique (cold vs BP). RESULTS: Facial nerve palsy rate increased with the extent of PGS (p < .0001). There were no differences in the risk of post-operative bleeding, salivary fistula and Frey's syndrome. BP resulted in a significant reduction of operation time (p = .04), postoperative bleeding (p = .001) and salivary fistula (p = .045) when compared with cold preparation. CONCLUSIONS: Ubiquitous available BP allows fast and safe PGS regardless its extent.

Pharyngotomy in head and neck squamous cell carcinoma: functional and oncological aspects.

BACKGROUND: Head and Neck Surgery constantly has to oppose non-invasive organ preservation methods and therefore should be evaluated especially with regard to clinical and functional outcome. We will discuss the role of pharyngotomy in the treatment of HNSCC. METHODS: Seventy-three patients with carcinoma of the oral cavity, oro-/hypopharynx and supraglottis underwent lateral/median pharyngotomy. Functional and oncological parameters were retrospectively assessed and set into clinical context. RESULTS: The 5-year recurrence-free-interval (RFI) was significantly higher with surgery and adjuvant radio(chemo)therapy (80%; mean RFI: 92 months) when compared to conservative treatment (68%; mean RFI: 68 months). The 5-year overall-survival (OS) after surgery and conservative treatment was 71% and 54%, respectively. Compared to other surgical techniques (mean RFI: 82 months), pharyngotomy demonstrated a significant higher 5-year RFI (mean RFI: 89 months). CONCLUSIONS: Pharyngotomy achieves good exposure and clear resection margins that result in a notably good oncological outcome with a minimum of functional loss. In particular, among UICC IV oropharyngeal HNSCC, pharyngotomy is superior in OS and RFI to conservative methods.

Mobile Health in Oncology: A Patient Survey About App-Assisted Cancer Care.

BACKGROUND: In the last decade, the health care sector has been enriched by numerous innovations such as apps and connected devices that assist users in weight reduction and diabetes management. However, only a few native apps in the oncological context exist, which support patients during treatment and aftercare. OBJECTIVE: The objective of this study was to analyze patients' acceptance regarding app use and to investigate the functions of an oncological app that are most required, and the primary reasons for patients to refuse app-assisted cancer care. METHODS: We designed and conducted a survey with 23 questions, inquiring patients about their technical knowledge and equipment, as well as the possible advantages and disadvantages, data transfer, and general functionality of an app. RESULTS: A total of 375 patients participated; the participation rate was 60.7% (375/618). Gender distribution was about 3:4 (female:male) with a median age of 59 years (range 18-92 years). Whereas 69.6% (261/375) of patients used mobile devices, 16.3% (61/375) did not own one, and 9.1% (34/375) only used a personal computer (PC). About half of the patients rated their usability skills as very good and good (18.9% 71/375; 35.2% 132/375), 23.5% (88/375) described their skills as intermediate, and 14.4% (54/375) as bad. Of all patients, 182 (48.5%, 182/375) were willing to send data to their treating clinic via an app, that is, to a server (61.0% 111/182) or as email (33.5%, 61/182). About two-thirds (68.7%, 125/182) believed that additional and regularly sent data would be an ideal complement to the standard follow-up procedure. Additionally, 86.8% (158/182) wished to be contacted by a physician when entered data showed irregularities. Because of lack of skills (34.4%, 56/163), concerns about the use of data (35.0%, 57/163), lack of capable devices (25.8%, 42/163), and the wish for personal contact with the treating physician (47.2%, 77/163), a total of 163 (43.5%, 163/375) patients refused to use an app. Pearson correlation showed a significant but mild relationship between age and app use (P=.03, r=-.12), favoring younger age; male gender correlated as well (P=.04; r=-.11). CONCLUSIONS: The results show that the introduction of mobile apps needs to follow different strategies depending on the patients' attitude. Age and gender seem to be the strongest predictive factors. For oncology patients, our survey showed that about half of the patients were willing to send data via an app supporting their treatment. In the future, clinical data such as quality of life and treatment satisfaction recorded by mobile health (mHealth) devices could be used to evaluate and improve therapy workflow. Furthermore, apps could support classical visits, document adverse effects, and remind patients of treatment dates or drug intake.

Do selective radiation dose escalation and tumour hypoxia status impact the loco-regional tumour control after radio-chemotherapy of head & neck tumours? The ESCALOX protocol.

BACKGROUND: Standard of care primary treatment of carcinoma of locally advanced squamous cell head and neck cancer (LAHNSCC) consists of platinum-based concomitant chemo-irradiation. Despite progress in the treatment of LAHNSCC using modern radiotherapy techniques the outcome remains still poor. Using IMRT with SIB the escalation of total dose to the GTV is possible with the aim to improve clinical outcome. This study tests the hypothesis if radiation dose escalation to the GTV improves 2-year-LRC and -OS after concomitant chemo-irradiation. METHODS: The ESCALOX trial is a prospective randomized phase III study using cisplatin chemo-irradiation and the SIB-IMRT concept in patients with LAHNSCC of the oral cavity, oropharynx or hypopharynx to escalate the total dose to the GTV up to 80.5 Gy. Chemotherapy is planned either in the 1st and 5th week (cisplatin 20 mg/m2/d d 1-5 and d 29-33) or weekly (cisplatin 40 mg/m2/d) during RT. RT is delivered as SIB with total doses of 80.5 Gy/70.0 Gy/56.0 Gy with 2.3 Gy/2.0 Gy and 1.6 Gy in the experimental arm and in the control arm with 70.0 Gy/56.0 Gy with 2.0 Gy and 1.6 Gy. A pre-study with dose escalation up to 77.0 Gy/70.0 Gy/56.0 Gy with 2.2 Gy/2.0 Gy and 1.6 Gy is demanded by the German federal office of radiation protection (BfS). In the translational part of the trial 100 of the randomised patients will be investigated by 18-F-FMiso-PET-CT for the presence and behaviour of tumor hypoxia twice in the week before treatment start. DISCUSSION: The primary endpoint of the pre-study is acute radiation induced toxicity. Primary endpoint of the main trial is 2-year-LRC. By using the dose escalation up to 80.5 Gy to the GTV of the primary tumor and lymph nodes > 2 cm a LRC benefit of 15% at 2 years should be expected. The ESCALOX trial is supported by Deutsche Forschungsgemeinschaft (DFG); Grant No.: MO-363/4-1. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 01212354 , EudraCT-No.: 2010-021139-15.

Integration of high-risk human papillomavirus into cellular cancer-related genes in head and neck cancer cell lines.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16- and HPV18-positive squamous cell carcinoma lines. METHODS: E6/E7 alternate transcripts were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites. RESULTS: All HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 head and neck squamous cell carcinoma (HNSCC) lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration. CONCLUSION: HPV integration into cancer-related genes occurred in 7 of 9 HPV-positive cell lines and of these 6 were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors. © 2017 Wiley Periodicals, Inc. Head Neck 39: 840-852, 2017.

Fractionated vs. single-fraction stereotactic radiotherapy in patients with vestibular schwannoma : Hearing preservation and patients' self-reported outcome based on an established questionnaire.

BACKGROUND: Stereotactic radiotherapy (RT) has been established as a valid treatment alternative in patients with vestibular schwannoma (VS). There is ongoing controversy regarding the optimal fractionation. Hearing preservation may be the primary goal for patients with VS, followed by maintenance of quality of life (QoL). METHODS: From 2002 to 2015, 184 patients with VS were treated with radiosurgery (RS) or fractionated stereotactic radiotherapy (FSRT). A survey on current symptoms and QoL was conducted between February and June 2016. RESULTS: Median follow-up after RT was 7.5 years (range 0-14.4 years). Mean overall survival (OS) after RT was 31.1 years, with 94 and 87% survival at 5 and 10 years, respectively [corrected]. Mean progression-free survival (PFS) was 13.3 years, with 5­ and 10-year PFS of 92%. Hearing could be preserved in RS patients for a median of 36.3 months (range 2.3-13.7 years). Hearing worsened in 17 (30%) cases. Median hearing preservation for FSRT was 48.7 months (range 0.0-13.8 years); 29 (23%) showed hearing deterioration. The difference in hearing preservation was not significant between RS and FSRT (p = 0.3). A total of 123/162 patients participated in the patient survey (return rate 76%). The results correlate well with the information documented in the patient files for tinnitus and facial and trigeminal nerve toxicity. Significant differences appeared regarding hearing impairment, gait uncertainty, and imbalance. CONCLUSION: These data confirm that RS and FSRT are comparable in terms of local control for VS. RS should be reserved for smaller lesions, while FSRT can be offered independently of tumor size. Patient self-reported outcome during follow-up is of high value. The established questionnaire could be validated in the independent cohort.

Primary tumor-associated expression of CXCR4 predicts formation of local and systemic recurrency in head and neck squamous cell carcinoma.

OBJECTIVES: Despite modern treatment regimens, overall survival in head and neck squamous cell carcinomas (HNSCC) is less than 50% due to local and systemic disease recurrency. The current study aims to identify molecular markers in primary tumor specimens that predict the risk for local and systemic recurrency at the time of initial diagnosis. METHODS: The study included clinic-pathological data of 1,057 HNSCC. MMP2/9, TIMP1/2, CXCR4, and CXCL12 immunohistochemistry was done in 150 randomly selected specimens. For statistics, we employed Chi square, Fisher exact, and Student's t-test. Overall survival (OS) was calculated by Kaplan-Meier and log-rank test. Prognostic variables were subsequently evaluated by Cox regression for forward selection. RESULTS: CXCR4 positive specimens demonstrated a significant increased risk for tumor recurrency associated death (rT: HR 10.07; p=0.001 / rN: HR 5.04; p=0.013 / rM: HR 2.49; p=0.029) when compared with their unaltered counterparts. Expression of MMP9, TIMP2, CXCR4, and CXCL12 was significantly increased in distant metastasized patients (p<0.0001) and showed significant cross-correlation. In addition, CXCR4 positivity was associated with an increased risk to die due to enhanced T or N status (T1/2 vs. T3/4: HR 5.78; p=0.017; N0 vs. N+: HR 5.18; p=0.033). CONCLUSION: CXCR4 positivity in tumor samples at initial diagnosis were associated with reduced overall survival, in particular with respect to increasing T/N status, local and systemic recurrency.

Use of Complementary and Alternative Medicine (CAM) as Part of the Oncological Treatment: Survey about Patients' Attitude towards CAM in a University-Based Oncology Center in Germany.

INTRODUCTION: To understand if and which patients would be open-minded to Complementary and Alternative Medicine (CAM) use parallel to their oncological treatment. Moreover, we sought to determine which methods are most accepted and which are the primary motivators to use CAM. METHODS: We developed and anonymously conducted a questionnaire for patients in the oncology center (TU Munich). Questions focus on different CAM methods, previous experiences, and willingness to apply or use CAM when offered in a university-based setting. RESULTS: A total of 171 of 376 patients (37.4% women, 62.0% men, 0.6% unknown) participated. This corresponds to a return rate of 45%. Median age was 64 years (17-87 years). Of all participants, 15.2% used CAM during their oncological therapy; 32.7% have used it in the past. The majority (81.9%) was not using CAM during therapy; 55.5% have not used CAM in the past respectively. The analysis revealed a significant correlation between education and CAM use during therapy (r = 0.18; p = 0.02), and CAM use in the past (r = 0.17; p = 0.04). Of all patients using CAM during therapy, favored methods were food supplements (42.3%), vitamins/minerals (42.3%), massage (34.6%). Motivations are especially the reduction of side effect and stress, the positive effect of certain CAM-treatments on the immune system and tumor therapy. Results showed no difference between women and men. Most patients not having had any experience with CAM complain about the deficiency of information by their treating oncologist (31.4%) as well as missing treatment possibilities (54.3%). CONCLUSION: Since many patients believe in study results demonstrating the efficacy of CAM, it stresses our task to develop innovative study protocols to investigate the outcomes of certain CAM on symptom reduction or other endpoints. Thus, prospective trials and innovative evidence-based treatment concepts to include CAM into high-end oncology is what patients demand and what a modern oncology center should offer.

Reduced volume SIB-IMRT/IGRT to head and neck cancer in elderly and frail patients: outcome and toxicity.

BACKGROUND: Especially elderly and frail patients have a limited ability to compensate for side effects of a radical treatment of head and neck malignancies. Limiting the target volume to the macroscopic disease, without prophylactic nodal irradiation, might present a feasible approach for these patients. The present work therefore aims evaluating an IMRT/IGRT -SIB concept for safety and efficacy. METHODS: The study retrospectively enrolled 27 patients with head and neck cancers treated between 01/2012 and 05/2015. We evaluated patient files for clinical status, concomitant diseases, treatment side, and treatment volumes as well as for side effects and tumor responses. To describe efficacy and risk factors for worse outcome and higher grade toxicities, we performed cox regression analysis as well as Kaplan-Meier survival time analysis. RESULTS: Median survival was 181 days, 75 % patients showed an early local response at six weeks of follow up. Most patients developed mild to moderate acute toxicities, only one patient with grade IV mucositis was seen. The grade of toxicities was correlated to the size of the PTV. Concomitant diseases, metastatic disease, and G3 Grading were indicators for worse prognosis. CONCLUSION: The IMRT/IGRT SIB concept is a safe and feasible radiotherapy concept for patients not able or not willing to undergo radical treatment.

Potential health risk of allergenic pollen with climate change associated spreading capacity: Ragweed and olive sensitization in two German federal states.

BACKGROUND: Global climate changes may influence the geographical spread of allergenic plants thus causing new allergen challenges. OBJECTIVE: Allergy patients from two German federal states were compared for their status quo sensitization to ragweed, an establishing allergen, olive, a non-established allergen, and the native allergens birch, mugwort, and ash. METHODS: Between 2011 and 2013, 476 adult allergy patients per region were recruited. Patients completed a questionnaire, participated in a medical interview, and underwent skin prick testing and blood withdrawal for analysis of specific IgE to allergen components (ISAC technology). Data on regional pollen load from 2006 to 2011 were acquired from the German Pollen Information Service Foundation. RESULTS: Prick test reactivity to ragweed and ash, respectively, was lower in Bavaria than in NRW (ragweed: p=0.001, aOR=0.54; ash: p=0.001, aOR=0.59), whereas prick test reactivity to olive was higher (p=0.000, aOR=3.09). Prick test reactivity to birch and mugwort, respectively, did not significantly differ. 1% (1/127) of patients with prick test reactivity to ragweed showed sIgE to Amb a 1, and 65% (86/132) of olive-but-not-ash reactive patients showed sIgE to Ole e 1 (NRW: 67%, Bavaria: 65%; p=0.823, OR=0.91). Regional differences in sensitization pattern were neither explainable by cross-reactivity to pollen pan-allergens nor non-exposure variables nor by reported plant population or pollen data. CONCLUSIONS: Spread of ragweed and particularly olive may result in prompt occurrence of allergic symptoms. Early identification of invasive allergens due to climate change does need time and spatial close meshed measurement of respective indicator allergens and sensitization pattern.

Outcome after pharyngeal reconstruction using pectoralis major and radial forearm flap after resection of pharyngeal and laryngeal squamous cell carcinomas.

The objective of this study is to assess the outcome after pharyngeal reconstruction using pectoralis major and radial forearm flaps in pharyngeal and laryngeal carcinomas. 90 patients who underwent flap surgery due to oro/-hypopharyngeal and laryngeal carcinomas were compared with 404 patients without pharyngeal reconstruction. Differences between the groups were analyzed using the Chi-square, Fisher exact, and the unpaired student's t test. Survival rates were calculated by Kaplan-Meier. Overall survival in oropharyngeal and hypopharyngeal/laryngeal cancer showed comparable results in patients with or without pharyngeal reconstruction (5-year: 53.4 vs. 64.2 %, p = 0.23; 5-year: 51.8 vs. 62.4 %, p = 0.94), while the survival time after flap surgery was significantly decreased (5-year: 44.8 vs. 62.4 %, p < 0.02; 5-year: 30.3 vs. 64.2 %, p = 0.07). Subgroup analysis attributed the worse survival after flap surgery to patients who underwent flap surgery due to functional deficits or recurrent disease (p = 0.002). In these patients, the median survival after flap surgery was 26 (hypopharyngeal/laryngeal cancer) or 13 months (oropharyngeal cancer) and associated with a significant increase in severe complications and hospitalization time (p < 0.0001). The hospitalization time correlated with the history of prior radiotherapy and the extent of surgery (r = 0.26; r = 0.3; p < 0.0001). Flap surgery in primary oropharyngeal and hypopharyngeal/laryngeal cancer showed an unaltered overall survival when compared with patients without reconstruction. Patients with recurrent disease or functional deficits demonstrated a significant decrease in survival combined with an increase of severe complications.