Tumor DNA-methylome derived epigenetic fingerprint identifies HPV-negative head and neck patients at risk for locoregional recurrence after postoperative radiochemotherapy.

Biomarkers with relevance for loco-regional therapy are needed in human papillomavirus negative aka HPV(-) head and neck squamous cell carcinoma (HNSCC). Based on the premise that DNA methylation pattern is highly conserved, we sought to develop a reliable and robust methylome-based classifier identifying HPV(-) HNSCC patients at risk for loco-regional recurrence (LR) and all-event progression after postoperative radiochemotherapy (PORT-C). The training cohort consisted of HPV-DNA negative HNSCC patients (n = 128) homogeneously treated with PORT-C in frame of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) multicenter biomarker trial. DNA Methylation analysis was performed using Illumina 450 K and 850 K-EPIC microarray technology. The performance of the classifier was integrated with a series of biomarkers studied in the training set namely hypoxia-, 5-microRNA (5-miR), stem-cell gene-expression signatures and immunohistochemistry (IHC)-based immunological characterization of tumors (CD3/CD8/PD-L1/PD1). Validation occurred in an independent cohort of HPV(-) HNSCC patients, pooled from two German centers (n = 125). We identified a 38-methylation probe-based HPV(-) Independent Classifier of disease Recurrence (HICR) with high prognostic value for LR, distant metastasis and overall survival (P < 10-9 ). HICR remained significant after multivariate analysis adjusting for anatomical site, lymph node extracapsular extension (ECE) and size (T-stage). HICR high-risk tumors were enriched for younger patients with hypoxic tumors (15-gene signature) and elevated 5-miR score. After adjustment for hypoxia and 5-miR covariates, HICR maintained predicting all endpoints. HICR provides a novel mean for assessing the risk of LR in HPV(-) HNSCC patients treated with PORT-C and opens a new opportunity for biomarker-assisted stratification and therapy adaptation in these patients.

Is antibiotic prophylaxis expendable in parotid gland surgery? A retrospective analysis of surgical site infection rates.

OBJECTIVES: To evaluate the rate of surgical site infection (SSI) and associated risk factors after parotid gland surgery including the impact of antibiotic prophylaxis. DESIGN: Retrospective single-centre clinical study. SETTING: Tertiary referral centre for head and neck surgery. PARTICIPANTS: Seven hundred and fifty four patients who underwent parotid gland surgery at the University Hospital Heidelberg, Germany, between 2007 and 2014 were enrolled in this study. Data on patient age, American Society of Anesthesiologists (ASA) classification system, smoking status, diabetes mellitus, operation time, and antibiotic prophylaxis were collected. Additionally, the National Healthcare Safety Network (NHSN) risk index was calculated. Association of these factors with SSI was evaluated in univariate analyses and a multivariate logistic regression model. MAIN OUTCOME MEASURES: Rate of SSI. RESULTS: Twenty four patients (3.2%) had an SSI according to the NHSN definition. In univariate analyses, only smokers (P = .048) and male patients (P = .01) had a significantly higher rate of SSI. Since the majority of smokers were men (62.3%), the effect of male gender, smoking, together with the NHSN risk index was further investigated as predictors of SSI within a logistic regression model. All three predictors showed a significant effect on SSI. CONCLUSIONS: Parotid gland surgery has a low rate of SSI. In our cohort, male gender, smoking and high NHSN risk index scores were significantly associated with SSI, whereas antibiotic prophylaxis had no protective effect.

Normative tonsillectomy outcome inventory 14 values as a decision-making tool for tonsillectomy.

PURPOSE: The study aimed to determine normative values for the Tonsillectomy Outcome Inventory 14 (TOI-14) in a healthy middle-European cohort. We also compared these generated values with TOI-14 scores from a patient population with recurrent tonsillitis (RT) and explored the factorial structure of the TOI-14. METHODS: We systematically studied the responses of healthy individuals (reference cohort) and patients with RT (clinical cohort) to the TOI-14 survey. The reference cohort contained 1000 participants, who were recruited using the Respondi panel for market and social science research. This subsample was quoted to the population distribution of the German Microcensus and selected from a non-probability panel. Tonsillitis patients were assessed before and 6 and 12 months after tonsillectomy. Data were analysed using principal component and exploratory factor analyses. RESULTS: The PCA revealed three TOI-14 domains (physiological, psychological and socio-economic), which explained 73% of the total variance. The reference cohort perceived a good quality of life (QOL) with a TOI-14 total score of 11.8 (physiological: 8.0, psychological: 5.8, and socio-economic subscale score: 13.9). TOI-14 scores were higher in the patient cohort, indicating that the TOI-14 discriminates between patients with RT and healthy individuals with no RT. Age and female gender significantly influenced the total TOI-14 score, especially in the psychological (age) and socio-economic (gender) subscales. CONCLUSION: We have developed a set of normative values that, together with the TOI-14, can determine the disease burden indicating tonsillectomy.

Clivus chordomas: Heterogeneous tumor extension requires adapted surgical approaches.

OBJECTIVE: Clivus chordomas are semi-malignant, but infiltratively growing tumors. Currently, a widely-accepted treatment concept encompasses maximal, but safe, surgical resection and radiotherapy. Caused by the size and the tumor extension, different surgical approaches, especially in recurrent cases, might be necessary. METHODS: Retrospective review of 50 patients on whom 70 surgeries were performed: 29 in primary and 41 in recurrent cases. Based on MRI images, all cases were asserted according to the size and the extension of the tumor. Used surgical approaches were evaluated. Postoperative complications, neurological function prior to and after the surgery, the extent of tumor resection on postoperative MR images were assessed and progression-free survival was calculated. RESULTS: Tumor size was estimated as small (< 5 cm3) in 8, as medium (5-20 cm3) in 21, as large (20-100 cm3) in 17, and as giant (> 100 cm3) in 4 patients. Most frequently used surgical approaches in primary cases were the transsphenoidal one and midfacial degloving (51.7 % and 17.2 %, respectively). In recurrent cases, dependent on the tumor extension, transsphenoidal (21.9 %), retrosigmoidal (29.3 %), and pterional (19.5 %) approaches, as well as midfacial degloving (17.1 %) were used. Due to the vast tumor extension and infiltration, gross total or near total resection could be achieved in 12 patients (24 %), only. There was no mortality and no major complications in primary cases. In recurrences, however, postoperative hemorrhages and strokes emerged in 4.9 % and 7.1 %. Minor complications occurred in 17.1 % and were dominated by CSF leaks (12.2 %), both in primary in recurrent cases. While most cranial nerve impairments were caused by tumor infiltration of the cavernous sinus, and hence have not improved by treatment, the sixth nerve palsy as a consequence of tumor mass compression, could significantly be improved by surgery. Following surgery, patients were subjected to radiotherapy (68.9 % for primary cases, and 36.6 % for recurrences) mainly with carbon ions. Overall, 5-year progression-free survival was 44.7 %. CONCLUSION: Caused by the heterogenous pattern of growth of clivus chordomas, surgical approaches should be chosen individually. Vast and infiltrative tumor extension constitute major limitations of surgical resection, and hence result in poor progression-frees survival.

[Prosthetic rehabilitation in the head and neck region]. / Epithetische Versorgung im Kopf-Hals-Bereich.

Implant-retained craniofacial prostheses (or epitheses) made of silicone are state of the art for prosthetic rehabilitation of facial defects. With the modern extraoral implant systems, prostheses may be securely anchored to the bone regardless of size and location of the defect. Prerequisite for successful implantation is the classical atraumatic surgical technique with avoidance of any thermal trauma to the bone. The treatment intention may be a temporary measure, a rescue procedure after failed (re)construction, or a definitive treatment option. This article gives an overview of the strategies in various facial regions stratified according to the age of the patient and the etiology of the defect. Moreover, prosthetic rehabilitation offers additional options for septal perforations, distorted and leaky tracheostomies, and treatment-resistant tracheoesophageal fistula.

Factors influencing time-dependent decannulation after pediatric tracheostomy according to the Kaplan-Meier method.

PURPOSE: The aim of this study was to determine whether there were differences in decannulation rates and time to decannulation in children depending on the indication for tracheostomy, age, and maturity at birth. STUDY DESIGN: Retrospective chart review and prospective interview by questionnaire. METHODS: The medical records of 106 pediatric patients (age 0-18 years) tracheostomized between January 1 1999 and January 1 2019 were reviewed. Patients were divided into three different groups depending on the indication for tracheostomy: unsafe airway (37.7%), long-term respiratory dependence (50.9%), or bronchopulmonary toilet for aspirations (11.3%). RESULTS: 40 patients were successfully decannulated. The time-dependent decannulation rate after 2 and 5 years was 28.3% and 40.5% for patients with an unsafe airway, 42.4% and 66.8% for patients with long-term respiratory dependence, and 41.7% and 70.8% for patients needing bronchopulmonary toilet, respectively. After 2 and 5 years, patients aged 0-12 months at the time of tracheostomy were decannulated in 13.1% and 50.2% of cases, 1-5-year-olds in 35.3% and 48.2% of cases, 6-10-year-olds in 70% and 70% of cases, and 11-18-year-olds in 66.6% and 66.6% of cases, respectively. However, in a multivariate analysis, prematurity was found to be the only significant unfavorable variable (p = 0.013). Maturely born patients had an odds ratio of 3.87 (95% CI 1.32-11.33) for successful decannulation. This effect was present only in the first 5 years of life. CONCLUSION: Factors indicating problems with decannulation are an unsafe airway, a young age at the time of tracheostomy, and prematurity at birth.

Tumor Control and Quality of Life in Skin Cancer Patients With Extensive Multilayered Nasal Defects.

OBJECTIVES: The reconstruction after nasal skin cancer (NSC) resection is often practiced differently. The objective of this study is to evaluate the influence of patient-, tumor- and management-related factors on the role of surgery and choice of reconstruction. METHODS: This was a monocentric retrospective study of patients who were diagnosed with a NSC (squamous cell or basal cell carcinoma) and suffered from an extended defect after ablative surgery between 2003 and 2013. Twenty-five patients were included. Tumors were staged using the Union for International Cancer Control (eighth edition) TNM classification for primary cutaneous skin cancer of the head and neck. Preferred treatment was surgery in all patients. Health-related quality of life (HRQoL) measurement was evaluated by one generic (36-Item Short Form Health Survey [SF-36]) and two organ-specific questionnaires (Rhinoplasty Outcome Evaluation [ROE] and Functional Rhinoplasty Outcome Inventory 17 [FROI-17]) after therapy. Survival data were estimated by the Kaplan-Meier method and statistical analysis was performed by log-rank, analysis of variance, Levene's and t-tests. The median follow-up time was 2.1 years. RESULTS: According to the Union for International Cancer Control classification, 13 of 25 tumors were staged as pT1 (52%), four as pT2 (16%), seven as pT3 (28%) and one as pT4a (4%). Seventy-two percent of patients (n=18) chose plastic reconstruction, and for the remaining 28% (n=7) of the patients opted for an implant-retained prosthesis. The overall survival was 69.5% after 5 years, the 5-year recurrence-free survival was 90.9% and the 5-year disease-specific survival was 100%. There was no significant difference in the HRQoL outcome between both rehabilitation methods. CONCLUSION: Surgery in NSC gives an excellent oncologic prognosis. Nasal reconstruction and prostheses are both very viable options depending on tumor stage and biology, the patient's wishes as well as the experience of the surgeon.

Somatic mutations and promotor methylation of the ryanodine receptor 2 is a common event in the pathogenesis of head and neck cancer.

Genomic sequencing projects unraveled the mutational landscape of head and neck squamous cell carcinoma (HNSCC) and provided a comprehensive catalog of somatic mutations. However, the limited number of significant cancer-related genes obtained so far only partially explains the biological complexity of HNSCC and hampers the development of novel diagnostic biomarkers and therapeutic targets. We pursued a multiscale omics approach based on whole-exome sequencing, global DNA methylation and gene expression profiling data derived from tumor samples of the HIPO-HNC cohort (n = 87), and confirmed new findings with datasets from The Cancer Genome Atlas (TCGA). Promoter methylation was confirmed by MassARRAY analysis and protein expression was assessed by immunohistochemistry and immunofluorescence staining. We discovered a set of cancer-related genes with frequent somatic mutations and high frequency of promoter methylation. This included the ryanodine receptor 2 (RYR2), which showed variable promoter methylation and expression in both tumor samples and cell lines. Immunohistochemical staining of tissue sections unraveled a gradual loss of RYR2 expression from normal mucosa via dysplastic lesion to invasive cancer and indicated that reduced RYR2 expression in adjacent tissue and precancerous lesions might serve as risk factor for unfavorable prognosis and upcoming malignant conversion. In summary, our data indicate that impaired RYR2 function by either somatic mutation or epigenetic silencing is a common event in HNSCC pathogenesis. Detection of RYR2 expression and/or promoter methylation might enable risk assessment for malignant conversion of dysplastic lesions.

Long-term quality of life and sensory impact of great auricular nerve preservation in parotid surgery as measured with the Parotidectomy Outcome Inventory-8.

OBJECTIVES: This study aimed to evaluate sensory dysfunction resulting from great auricular nerve (GAN) sacrifice versus preservation in parotid surgery for benign lesions and its imact on long-term health-related quality of life (QOL). DESIGN: Retrospective. SETTING/MAIN OUTCOME MEASURES: Participants were divided into two groups (GAN and non-GAN), and both short-term (two postoperative weeks) and long-term (at least 5 years) QOL were assessed. The second item of the Parotidectomy Outcome Inventory-8 (POI-8) was used to analyse postoperative sensory loss. All items of the POI-8 questionnaire were used to determine health-related QOL.We used t test for dependent samples and Mann-Whitney U-test to compare patient groups PARTICIPANTS: A total of 137 patients (65 male and 72 female) enrolled in this study. Average age at the time of surgery was 53 years (±12.8). RESULTS: The GAN preservation group had significantly better sensation than the GAN sacrifice in short term (2.8 vs 2.1; P = 0.017). Both groups experienced improved sensation in the long term, and there was a trend towards better QOL in the GAN-preservation group. However, the difference in sensation was not statistically significant (1.7 vs 1.3; P = 0.145). Health-related QOL also increased in the long term (compared to short term) for both groups (7.6 ± 6.2 to 12 ± 7.6; P < 0.0001) postoperatively. GAN preservation did not significantly improve sensation in long term, nor did it increase health-related QOL postoperatively. CONCLUSION: Although GAN preservation was easily feasible, it only improved sensation in short term. We report a negative result: GAN preservation did not significantly improve sensation in long-term, nor did it increase health-related QOL postoperatively when compared to GAN sacrifice.

Auricular Prostheses in Microtia.

The progress made in the development of the silicones and percutaneous titanium implants allow for rehabilitation of patients with microtia with an inconspicuous auricular prosthesis. The art of making the prosthesis by the dedicated anaplastologist is the key for the success of this approach. Most patients with microtia desire camouflage. The greatest advantage of the auricular prosthesis is that it can be manufactured as a mirrored replica of the opposite side. The outcome is predictable. Computer science with virtual planning and rapid prototyping is about to revolutionize the process of prosthetic auricular rehabilitation.

Factors Influencing the Incidence of Severe Complications in Head and Neck Free Flap Reconstructions.

BACKGROUND: Complications after head and neck free-flap reconstructions are detrimental and prolong hospital stay. In an effort to identify related variables in a tertiary regional head and neck unit, the microvascular reconstruction activity over the last 5 years was captured in a database along with patient-, provider-, and volume-outcome-related parameters. METHODS: Retrospective cohort study (level of evidence 3), a modified Clavien-Dindo classification, was used to assess severe complications. RESULTS: A database of 217 patients was created with consecutively reconstructed patients from 2009 to 2014. In the univariate analysis of severe complications, we found significant associations (P < 0.05) between type of flap used, American Society of Anesthesiologists classification, T-stage, microscope use, surgeon, flap frequency, and surgeon volume. Within a binomial logistic regression model, less frequently versus frequently performed flap (odds ratio [OR] = 3.2; confidence interval [CI] = 2.9-3.5; P = 0.000), high-volume versus low-volume surgeon (OR = 0.52; CI = -0.22 to 0.82; P = 0.007), and ASA classification (OR = 2.9; CI = 2.4-3.4; P = 0.033) were retained as independent predictors of severe complications. In a Cox-regression model, surgeon (P = 0.011), site of reconstruction (P = 0.000), T-stage (P = 0.001), and presence of severe complications (P = 0.015) correlated with a prolonged hospitalization. CONCLUSIONS: In this study, we identified a correlation of patient-related factors with severe complications (ASA score) and prolonged hospital stay (T-stage, site). More importantly, we identified several provider- (surgeon) and volume-related (frequency with which a flap was performed and high-volume surgeon) factors as predictors of severe complications. Our data indicate that provider- and volume-related parameters play an important role in the outcome of microvascular free-flap procedures in the head and neck region.

Modified facelift incision for partial parotidectomy versus bayonet-shaped incision: a comparison using visual analog scale.

The aim of this study is to show differences between a modified facelift incision (MFI) for partial parotidectomy versus a bayonet-shaped incision (BSI). 24 patients presenting with a parotid tumor were surgically treated with a partial parotidectomy using a MFI. We generated a "matched pair control group" regarding age, tumor size and gender, who received a BSI. A questionnaire was sent to all patients and relevant data reviewed. The cosmetic satisfaction on a VAS with a MFI was 9.74 (±0.47) compared to BSI with 7.63 (±2.44, p = 0.004). The scoring in the two subgroups "visible scar" and "people noticed my surgery" was significantly better in the MFI group The postoperative skin numbness, skin depression, facial nerve function postoperatively showed no statistical differences. The MFI for parotid tumors has a better outcome than the BSI regarding cosmetic satisfaction and visible scarring.

High-LET radiotherapy for adenoid cystic carcinoma of the head and neck: 15 years' experience with raster-scanned carbon ion therapy.

PURPOSE: Locoregional control (LC) in malignant salivary gland tumors is dose-dependent, initial results with particle therapy were promising. We report our experience with raster-scanned, intensity-controlled carbon ion therapy (C12) and IMRT in 309 patients with pathologically confirmed adenoid cystic carcinoma (ACC) of the head and neck. PATIENTS AND METHODS: Treatment records of patients treated with C12 between 08/1998 and 05/2013 were evaluated regarding tumor stage, treatment, toxicity (CTCAE v3), LC, progression-free survival (PFS) and overall survival (OS). Response assessment was carried out according to RECIST1.1. RESULTS: Tumor stages were mostly advanced (T4a/b: 60%, macroscopic disease: 71%), most common sites of origin were the paranasal sinus (37%). At a median follow-up at 33.9 months, LC, PFS, and OS at 3 and 5 year estimates are 83.7%/58.5%, 67.8%/56.1%, and 88.9%/74.6%. LC correlates with T-stage but neither nodal stage, age, relapse state, nor margin status. RECIST did not correlate with LC or survival rates. CONCLUSION: IMRT plus C12 boost results in good control and survival rates at moderate toxicity. Margin status did not correlate with LC in T4 tumors, extensive and potentially mutilating surgical procedures may have to be re-evaluated. RECIST assessment did not correlate with either LC or survival rates; potentially more meaningful radiological parameters need to be developed.

Raster-scanned intensity-controlled carbon ion therapy for mucosal melanoma of the paranasal sinus.

BACKGROUND: The purpose of this study was to evaluate the use of raster-scanned intensity-controlled carbon ion therapy (ICCT) in the treatment of mucosal melanoma of the paranasal sinus. METHODS: Patients received combined intensity-modulated radiotherapy (IMRT) plus carbon ion (C12). Records of 18 consecutive patients treated between 2009 and 2013 were analyzed retrospectively regarding toxicity (Common Terminology Criteria for Adverse Events, version 4), treatment response (Response Evaluation Criteria in Solid Tumors [RECIST]), and control/survival rates. RESULTS: Most patients had advanced disease (T4, 94%; gross residual disease, 78%). Median dose was 74 GyE (median boost volume = 157 mL). C12 treatments were planned as ICCT, no concurrent chemotherapy was administered. Grade III or higher late toxicity was not observed. Overall survival (OS), progression-free survival (PFS), and locoregional control at 3 years were 16.2%, 0%, and 58.3%, respectively (median follow-up, 18 months). Resection status did not impact locoregional control or survival rates. CONCLUSION: ICCT results in promising locoregional control at mild toxicity. OS is poor because of the occurrence of distant metastases; therefore, addition of systemic components to primary treatment should be investigated. © 2015 Wiley Periodicals, Head Neck 38: E1445-E1451, 2016.

The Role of Auricular Prostheses (Epitheses) in Ear Reconstruction.

The artwork of making the epithesis by the dedicated anaplastologist is the prerequisite of acceptance by the patient and the key for success of this approach. However, computer science is helping with virtual planning and rapid prototyping, and it is likely to revolutionize this process in the near future. One of the advantages of the auricular prostheses is that it can be manufactured as a mirrored replica of the opposite side (if normal or near normal). Furthermore, the results are predictable, and may be shown to the patient before surgery. The developments of various implant systems allow secure retention even in unfavorable anatomic situations as in the ideally pneumatized mastoid process. The advantage of the plate systems is that they spread the loading forces to multiple smaller bone screws, rendering it thereby resistant to torque with abutment insertion or magnet change. Auricular prostheses fulfill three roles: (1) temporary measure, (2) rescue procedure in failed auricular (re)construction, and (3) definitive treatment option. Conventional retention by medical adhesives, sometimes helped by making use of the remnant, keeps its place in the use as a temporary measure or if the patient declines surgery. Today, implant-retained auricular prostheses made of silicone are state of the art for prosthetic rehabilitation of patients with auricular defects.

An EGF receptor targeting Ranpirnase-diabody fusion protein mediates potent antitumour activity in vitro and in vivo.

Cytotoxic ribonucleases such as the leopard frog derivative Ranpirnase (Onconase(®)) have emerged as a valuable new class of cancer therapeutics. Clinical trials employing single agent Ranpirnase in cancer patients have demonstrated significant clinical activity and surprisingly low immunogenicity. However, dose-limiting toxicity due to unspecific uptake of the RNase into non-cancerous cells is reached at relatively low concentrations of > 1 mg/m(2). We have in the present study generated a dimeric anti-EGFR Ranpirnase-diabody fusion protein capable to deliver two Ranpirnase moieties per molecule to EGFR-positive tumour cells. We show that this compound mediated far superior efficacy for killing EGFR-positive tumour cells than a monomeric counterpart. Most importantly, cell killing was restricted to EGFR-positive target cells and no dose-limiting toxicity of Ranpirnase-diabody was observed in mice. These data indicate that by targeted delivery of Ranpirnase non-selective toxicity can be abolished and suggests Ranpirnase-diabody as a promising new drug for therapeutic interventions in EGFR-positive cancers.

Generation of "LYmph Node Derived Antibody Libraries" (LYNDAL) for selecting fully human antibody fragments with therapeutic potential.

The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected "LYmph Node Derived Antibody Libraries" (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro,the most potent antibody neutralized 50% HSV-2 at 4.5 nM as a dimeric (scFv)2. We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential.

Assessment of peri- and postoperative complications and Karnofsky-performance status in head and neck cancer patients after radiation or chemoradiation that underwent surgery with regional or free-flap reconstruction for salvage, palliation, or to improve function.

BACKGROUND: Surgery after (chemo)radiation (RCTX/RTX) is felt to be plagued with a high incidence of wound healing complications reported to be as high as 70%. The additional use of vascularized flaps may help to decrease this high rate of complications. Therefore, we examined within a retrospective single-institutional study the peri--and postoperative complications in patients who underwent surgery for salvage, palliation or functional rehabilitation after (chemo)radiation with regional and free flaps. As a second study end point the Karnofsky performance status (KPS) was determined preoperatively and 3 months postoperatively to assess the impact of such extensive procedures on the overall performance status of this heavily pretreated patient population. FINDINGS: 21 patients were treated between 2005 and 2010 in a single institution (17 male, 4 female) for salvage (10/21), palliation (4/21), or functional rehabilitation (7/21). Overall 23 flaps were performed of which 8 were free flaps. Major recipient site complications were observed in only 4 pts. (19%) (1 postoperative haemorrhage, 1 partial flap loss, 2 fistulas) and major donor site complications in 1 pt (wound dehiscence). Also 2 minor donor site complications were observed. The overall complication rate was 33%. There was no free flap loss. Assessment of pre- and postoperative KPS revealed improvement in 13 out of 21 patients (62%). A decline of KPS was noted in only one patient. CONCLUSIONS: We conclude that within this (chemo)radiated patient population surgical interventions for salvage, palliation or improve function can be safely performed once vascularised grafts are used.