TRIM21 Expression as a Prognostic Biomarker for Progression-Free Survival in HNSCC.

Patients with head and neck squamous cell carcinoma (HNSCC) continue to have a rather poor prognosis. Treatment-related comorbidities have negative impacts on their quality of life. TRIM21 is a cytosolic E3 ubiquitin ligase that was initially described as an autoantigen in autoimmune diseases and later associated with the intracellular antiviral response. Here, we investigated the role of TRIM21 as a biomarker candidate for HNSCC in predicting tumor progression and patient survival. We analyzed TRIM21 expression and its association with clinical-pathological parameters in our HNSCC cohort using immunohistochemistry. Our HNSCC cohort included samples from 419 patients consisting of primary tumors (n = 337), lymph node metastases (n = 156), recurrent tumors (n = 54) and distant metastases (n = 16). We found that cytoplasmic TRIM21 expression was associated with the infiltration of immune cells into primary tumors. In addition, TRIM21 expression was significantly higher in primary tumors than in lymph node metastases, and increased TRIM21 expression was correlated with shorter progression-free survival in HNSCC patients. These results suggest that TRIM21 could be a new biomarker for progression-free survival.

Elevated LSD1 and SNAIL Expression Indicate Poor Prognosis in Hypopharynx Carcinoma.

Head and neck squamous cell carcinomas (HNSCC) are among the most common cancers worldwide and are associated with a poor prognosis for patients. Among HNSCC, those originating in the hypopharynx have the worst prognosis. The histone demethylase LSD1 has been shown to promote cancer initiation, progression, and relapse through various mechanisms and is upregulated in many cancer tissues. LSD1 physically interacts with SNAIL and is required for SNAIL mediated transcriptional repression. Previous studies of the prognostic value of LSD1 in HNSCC have been limited in their analysis of sub-sites, and a correlation between LSD1 and SNAIL has not been shown in HNSCC patient samples. Here we used a large, representative, and clinically well-characterized cohort of 339 HNSCC patients to investigate the co-expression of LSD1 and SNAIL and their prognostic value in all HNSCC using immunohistochemical staining. Elevated LSD1 expression correlated with advanced tumor stage and poor progression-free survival (PFS) in HNSCC originating in the hypopharynx. Overexpression of the transcription factor SNAIL independently correlated with worse overall survival (OS) and PFS in HNSCC in general and prominently in tumors of the hypopharynx. Furthermore, increased LSD1 expression significantly correlated with elevated SNAIL expression in patient samples. Therefore, the presented data implicates LSD1 and SNAIL as independent prognostic biomarkers.

EVI1 as a Marker for Lymph Node Metastasis in HNSCC.

BACKGROUND: HNSCC is the sixth most common cancer in humans and has still a very poor prognosis. The treatment methods so far are very often associated with mutilation and impairment in the quality of life. Except for p16 expression, there are no reliable prognostic markers in HNSCC so far. Ecotropic Viral Integration Site 1 (EVI1) is a well-described prognostic marker in leukemia and different types of solid cancers. In these, a high EVI1 expression is associated with a poor prognosis. In HNSCC, it is not known so far if EVI1 has any prognostic relevance. MATERIALS AND METHODS: We used our representative tissue cohort of 389 primary HNSCCs, of which 57.2% had one or more lymph node metastases. Here EVI1 expression was analyzed via immunohistochemistry and correlated with the clinical characteristics of these patients. RESULTS: Although in HNSCC EVI1 expression does not predict poor survival, a high EVI1 expression in the primary tumor correlates with a lymph node metastatic disease. CONCLUSION: Consequently, EVI1 may serve as a biomarker to predict an occult lymph node metastasis in a clinical nodal negative (cN0) HNSCC.

CDK19 as a Potential HPV-Independent Biomarker for Recurrent Disease in HNSCC.

The Mediator complex is a central integrator of transcription and a hub for the regulation of gene expression. Cyclin dependent kinase (CDK) 19 and its paralog CDK8 are part of its kinase domain and contribute to cancer progression in different cancer entities. STAT1 is an important immune modulator and a downstream substrate of CDK8/CDK19 mediated phosphorylation. So far, little is known about CDK19's role in head and neck squamous cell carcinoma (HNSCC) progression, its link to STAT1 activity, and related immune modulation. Immunohistochemistry for CDK19, activated pSTAT1, and PD-L1, known to be affected by STAT1, was conducted on samples of 130 primary tumors, 71 local recurrences, 32 lymph node metastases, and 25 distant metastases of HNSCC. Compared to primary tumors, CDK19 is overexpressed in local recurrences and distant metastases as well as in primary tumors that developed local recurrence after initial therapy. Patients with high-CDK19-expressing primary tumors have a significantly shorter disease-free survival. CDK19 expression correlates with pSTAT1 expression in primary tumors associated with recurrent disease, local recurrent tumors, lymph node metastases, and distant metastases. pSTAT1 expression correlates with PD-L1 expression in recurrent tumors. Our findings identify CDK19 as a potential biomarker in HNSCC to predict recurrent disease and support recent developments to target CDK19 and its paralog CDK8 in advanced cancer.

NR2F6 as a Prognostic Biomarker in HNSCC.

Head and neck squamous cell carcinoma (HNSCC)is the 6th most common cancer in humans worldwide and is associated with a poor prognosis for patients. NR2F6 has been identified as an immune checkpoint molecule in tumor-infiltrating T lymphocytes and is associated with a poor prognostic outcome in various cancers. The prognostic value of NR2F6 in HNSCC has not been described yet. We used a large, representative and clinically well-characterized cohort of 383 HNSCC patients, of which 22.4% developed a local recurrence. The NR2F6 expression was analyzed by using immunohistochemistry and was afterward correlated with clinical characteristics and clinicopathological features of HNSCC patients. Primary tumors from patients who develop a local recurrence have a higher NR2F6 expression than primary tumors which do not develop a local recurrence. Furthermore, a high NR2F6 expression is associated with poorer recurrence-free survival, although there is no correlation with overall survival. NR2F6 expression is independent of the T stage and UICC stage. NR2F6 might be a new prognostic biomarker for the early detection of local recurrences in HNSCC patients. Therefore, it may help to improve the recognition of patients who would benefit from more frequent follow-up examinations.

DNA methylation-based reclassification of olfactory neuroblastoma.

Olfactory neuroblastoma/esthesioneuroblastoma (ONB) is an uncommon neuroectodermal neoplasm thought to arise from the olfactory epithelium. Little is known about its molecular pathogenesis. For this study, a retrospective cohort of n = 66 tumor samples with the institutional diagnosis of ONB was analyzed by immunohistochemistry, genome-wide DNA methylation profiling, copy number analysis, and in a subset, next-generation panel sequencing of 560 tumor-associated genes. DNA methylation profiles were compared to those of relevant differential diagnoses of ONB. Unsupervised hierarchical clustering analysis of DNA methylation data revealed four subgroups among institutionally diagnosed ONB. The largest group (n = 42, 64%, Core ONB) presented with classical ONB histology and no overlap with other classes upon methylation profiling-based t-distributed stochastic neighbor embedding (t-SNE) analysis. A second DNA methylation group (n = 7, 11%) with CpG island methylator phenotype (CIMP) consisted of cases with strong expression of cytokeratin, no or scarce chromogranin A expression and IDH2 hotspot mutation in all cases. T-SNE analysis clustered these cases together with sinonasal carcinoma with IDH2 mutation. Four cases (6%) formed a small group characterized by an overall high level of DNA methylation, but without CIMP. The fourth group consisted of 13 cases that had heterogeneous DNA methylation profiles and strong cytokeratin expression in most cases. In t-SNE analysis, these cases mostly grouped among sinonasal adenocarcinoma, squamous cell carcinoma, and undifferentiated carcinoma. Copy number analysis indicated highly recurrent chromosomal changes among Core ONB with a high frequency of combined loss of chromosome 1-4, 8-10, and 12. NGS sequencing did not reveal highly recurrent mutations in ONB, with the only recurrently mutated genes being TP53 and DNMT3A. In conclusion, we demonstrate that institutionally diagnosed ONB are a heterogeneous group of tumors. Expression of cytokeratin, chromogranin A, the mutational status of IDH2 as well as DNA methylation patterns may greatly aid in the precise classification of ONB.

Correction to: DNA methylation-based reclassification of olfactory neuroblastoma.

In the original publication, the second name of the twentieth author was incorrect. It should read as 'Miguel Sáinz-Jaspeado'. The original publication of the article has been updated to reflect the change. This correction was authored by Ulrich Schüller on behalf of all authors of the original publication.

Prognostic impact of the loss of E-cadherin and de novo expression of N-cadherin at the invasive front of primary and recurrent oral squamous cell carcinoma.

The epithelial-mesenchymal transition (EMT) is a biological mechanism in multiple pathophysiological diseases. Related alterations in cadherin expression play a crucial role in carcinogenesis, progression, angiogenesis, and immune response. EMT cells exhibit a transition from an epithelial to a mesenchymal phenotype (cadherin-switch). This process is characterized by the de novo development of N-cadherin (N-CAD), which replaces E-cadherin (E-CAD) and signifies an increased migratory capacity and malignant transformation. The cadherin switch is a hallmark of EMT and has been studied in various cancer entities. We predicted that the cadherin switch in the primary and recurrent oral squamous cell carcinoma (re-OSCC) tissues is an inherent characteristic of the tumor, affects the biologic behavior, and further reflects the post-recurrence survival outcome of these patients. Survival outcome was analyzed by calculating the post-recurrence survival of the high-risk group and correlating the standardized h-score-based IHC expression of both cadherin types with the clinical follow-up. 94 patients with re-OSCC were observed within the cohort. Tissue samples from both primary and recurring tumors were collected. There was a significant association between loss of E-CAD expression and both oral cancer-specific and overall survival, (HR=2.72, CI:1.50-4.95, p=0.001) and (HR=3.84, CI:1.93-7.63, p=0.001), respectively, for expression loss higher than 60%. There was no statistically significant correlation between N-CAD de novo expression and Overall, oral cancer-specific and disease-free post-recurrence survival. The current study clearly shows that cadherin-switch, identified as E-CAD loss and N-CAD de novo expression in the invasion front of a re-OSCC, appears to be an inherent histological hallmark that does not change from primary manifestation to recurrence within the same tumor, regardless of the form of adjuvant therapy used for the primary tumor. The loss of E-CAD expression in re-OSCC is an independent risk factor for poor survival, and may be used to stratify therapy and de/escalate the multimodal treatment.

Identifying Predictive Biomarkers for Head and Neck Squamous Cell Carcinoma Response.

The 5-year survival rate for head and neck squamous cell carcinoma (HNSCC) is approximately 65%. In addition to radio-chemotherapy, immunotherapy is an approach in the treatment of advanced HNSCC. A better understanding of the immune context would allow personalized treatment by identifying patients who are best suited for different treatment options. In our discovery cohort, we evaluated the expression profiles of CMTM6, PD-L1, CTLA-4, and FOXP3 in 177 HNSCCs from Caucasian patients of all tumor stages and different treatment regimens, correlating marker expression in tumor and immune cells with outcomes. Patients with CMTM6high-expressing tumors had a longer overall survival regardless of treatment. This prognostic benefit of CMTM6 in HNSCC was validated in an independent cohort. Focusing on the in the discovery cohort (n = 177), a good predictive effect of CMTM6high expression was seen in patients receiving radiotherapy (p = 0.07; log rank), but not in others. CMTM6 correlated with PD-L1, CTLA-4 and FOXP3 positivity, with patients possessing CMTM6high/FOXP3high tumors showing the longest survival regardless of treatment. In chemotherapy-treated patients, PD-L1 positivity was associated with longer progression-free survival (p < 0.05). In the 27 patients who received immunotherapy, gene expression analysis revealed lower levels of CTLA-4 and FOXP3 with either partial or complete response to this treatment, while no effect was observed for CMTM6 or PD-L1. The combination of these immunomodulatory markers seems to be an interesting prognostic and predictive signature for HNSCC patients with the ability to optimize individualized treatments.

Correlation of Intra-tumoral and Peripheral PD-1/PD-L1 Immunity in Head and Neck Cancer.

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous malignant disease of the oral cavity, pharynx, and larynx. HNSCC cells evade the host immune system through alterations in their immunogenicity, production of immunosuppressive mediators, and induction of immunomodulatory cell types. The immune status of solid HNSCC can be considered as hot, cold, or excluded for each patient individually, based on the distribution of tumor infiltrating immune cells. In this context immunotherapies based on the blockade of checkpoint molecules programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) have significantly improved therapeutic outcomes in different cancer types. In HNSCC, intra-tumoral expression levels of PD-L1 are used for decision making in checkpoint inhibitor treatment. The significance of PD-L1 as a prognostic indicator is still controversial because both PD-1 and PD-L1 are also expressed in different types of circulating immune cells and the interaction of systemic and intra-tumoral cell-type-specific expression patterns of checkpoint molecules PD-1/PD-L1 has not yet been fully unveiled. MATERIALS AND METHODS: Using immunohistochemical (IHC) staining and flow cytometry, we correlated the expression patterns of the checkpoint molecules PD1/PD-L1 in peripheral blood CD14/CD16 monocytes and CD4/CD8 T cells with intra-tumoral conditions in patients with head and neck cancer. RESULTS/CONCLUSION: Our data demonstrate significant connections between systemic and intra-tumoral PD-1/PD-L1 immune patterns, both of which may serve as promising combined biomarkers for treatment decisions in patients with head and neck cancer.

Deglycosylation of pathological specimens alters performance of diagnostic PDL1 antibodies.

Immunohistochemical (IHC) predictive quantitation of PDL1 expression is obligatory in many cancer entities with improved response to immune checkpoint inhibition in PDL1-positive subgroups. With recent demonstration of increased positivity rates after enzymatic deglycosylation in breast cancer specimens, a comparative analysis with two different antibodies and extended controls was performed in a cohort of head and neck squamous cell cancer samples (HNSCC).Formalin-fixed paraffin-embedded tissue from HNSCC specimens was used for initial on-slide method optimization based on the PNGase F assay. SDS-PAGE and immunoblotting with the PDL1 antibody 28-8 was performed to evaluate deglycosylation efficiency. A tissue micro array of n = 527 tissue cores of 181 patients with HNSCC was used to determine the effects of deglycosylation on staining pattern and intensity with PDL1 antibodies 28-8 and E1L3N.Successful on-slide deglycosylation with PNGase F was confirmed by immunoblot but varied across replicates. Using E1L3N (intracellular binding domain, most probably not glycosylated), mean signal intensity as well as the fraction of PDL1 positive cells was increased by deglycosylation. Opposite effects were observed with 28-8 (extracellular binding domain, glycosylated).Deglycosylation reduces diagnostic performance of the PDL1 antibody 28-8. In contrast, effects for E1L3N are complex and probably involve reduction of off-target binding leading to specifically improved signal intensity. However, enzymatic deglycosylation adds further variance to IHC.

Increased Abundances of CD16+ Non-Classical Monocytes Accompany with Elevated Monocytic PD-L1 and CD4+ T Cell Disturbances in Oropharyngeal Cancer.

BACKGROUND: Patients with human papilloma virus (HPV)-related oropharyngeal cancer have a better prognosis than nonvirally associated patients, most likely because of better immune responses. Increased infiltration of T lymphocytes into the oropharyngeal tumor tissue has been observed, but the dynamics of circulating lymphocytes and monocytes are not fully understood. The aim of this study was to understand the population dynamics of circulating monocyte subsets in oropharyngeal cancer (OPC) patients with regard to the clinicopathological parameters and accompanying immunological consequences in view of the CD4/CD8 T cell subset composition, and the expression of checkpoint pathway proteins programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1). MATERIALS AND METHODS: The abundance of circulating monocyte subsets and peripheral blood CD4/CD8 T cells of oropharyngeal cancer patients and their PD-L1 and PD-1 expression levels were analyzed by flow cytometry. RESULTS: The studied oropharyngeal cancer patients revealed heterogeneous individual redistributions of CD14++CD16- (classical), CD14++CD16+ (intermediate), and CD14dim+CD16+ (nonclassical) monocyte subsets compared with healthy donors. These differences in monocyte subset alterations were independent in patients with TNM or HPV status but entailed further immunological consequences. Increased percentages of nonclassical monocytes significantly correlated with increased levels of monocytic PD-L1 expression. We observed significantly decreased levels of CD4+ effector T cells, which were accompanied by increased CD4+ effector memory T cells in OPC patients compared with healthy donors, each having a stronger effect in patients with decreased levels of classical monocytes. CONCLUSION: We conclude that oropharyngeal cancer, as a malignancy from a lymphoid-tissue-rich anatomical region, has a strong systemic impact on the differentiation and regulation of circulating innate and adaptive immune cells. Further comprehensive investigations are required for the possible future usability of the described immunological alterations as bioliquid parameters for prognosis or therapy response prediction.

CDK7 Predicts Worse Outcome in Head and Neck Squamous-Cell Cancer.

HNSCC is the sixth most common cancer worldwide and the prognosis is still poor. Here, we investigated the prognostic implications of CDK7 and pMED1. Both proteins affect transcription, and their expression is altered throughout different tumor entities. pMED1 is phosphorylated by CDK7. Importantly, CDK7 and MED1 have been ascribed prognostic implications by various studies. However, their prognostic value in head and neck squamous-cell cancer (HNSCC) remains elusive. We applied immunohistochemical staining of CDK7 and pMED1 on our large and clinically well-characterized HNSCC tissue cohort comprising 419 patients. Software-aided quantification of staining intensity was performed as a measure of protein expression. The following results were linked to the clinicopathological features of our cohort and correlated in different tissue types (primary tumor, lymph node metastasis, distant metastasis, recurrence). Upregulation CDK7 was associated with worse 5-year overall survival as well as disease-free survival in HNSCC while being independent of other known prognostic factors such as p16-status. Also, CDK7 expression was significantly elevated in immune cell infiltrated tumors. In HNSCC CDK7 might serve as a novel prognostic marker to indicate the prognosis of patients. Furthermore, in vitro studies proved the feasibility of CDK7 inhibition with attenuating effects on cell proliferation underlining its remarkable translational potential for future therapeutic regimes.

TRIM24 Expression as an Independent Biomarker for Prognosis and Tumor Recurrence in HNSCC.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are among the most common cancers in humans worldwide and have a rather poor prognosis. TRIM24 has various intracellular functions and was identified in other cancer entities as a poor prognostic factor for patients. METHODS: The expression of TRIM24 was evaluated by using immunohistochemistry. We used a large and representative cohort of 341 HNSCC patients. Data derived from immunohistochemistry evaluation was correlated with clinicopathological data from HNSCC patients. RESULTS: The TRIM24 expression in HNSCC primary tumors is negatively correlated with the p16 status of the tumor tissues. Primary tumors of patients who developed a local recurrence were significantly more often positive for TRIM24. Kaplan-Meier analyses and Cox regression showed that patients with TRIM24 expressing tumors have significantly worse overall survival and progression-free survival and that TRIM24 expression is independent of other established risk factors. CONCLUSIONS: TRIM24 might be a new prognostic biomarker for the survival prognosis and early detection of local recurrences in HNSCC patients. It could be used for risk stratification of HNSCC patients and to identify those patients who are more prone to develop a local recurrence and therefore could profit from more frequent follow-up examinations.

Therapy-Related Transcriptional Subtypes in Matched Primary and Recurrent Head and Neck Cancer.

PURPOSE: The genetic relatedness between primary and recurrent head and neck squamous cell carcinomas (HNSCC) reflects the extent of heterogeneity and therapy-driven selection of tumor subpopulations. Yet, current treatment of recurrent HNSCC ignores the molecular characteristics of therapy-resistant tumor populations. EXPERIMENTAL DESIGN: From 150 tumors, 74 primary HNSCCs were RNA sequenced and 38 matched primary/recurrent tumor pairs were both whole-exome and RNA sequenced. Transcriptome analysis determined the predominant classical (CL), basal (BA), and inflamed-mesenchymal (IMS) transcriptional subtypes according to an established classification. Genomic alterations and clonal compositions of tumors were evaluated from whole-exome data. RESULTS: Although CL and IMS subtypes were more common in primary HNSCC with low recurrence rates, the BA subtype was more prevalent and stable in recurrent tumors. The BA subtype was associated with a transcriptional signature of partial epithelial-to-mesenchymal transition (p-EMT) and early recurrence. In 44% of matched cases, the dominant subtype changed from primary to recurrent tumors, preferably from IMS to BA or CL. Expression analysis of prognostic gene sets identified upregulation of hypoxia, p-emt, and radiotherapy resistance signatures and downregulation of tumor inflammation in recurrences compared with index tumors. A relevant subset of primary/recurrent tumor pairs presented no evidence for a common clonal origin. CONCLUSIONS: Our study showed a high degree of genetic and transcriptional heterogeneity between primary/recurrent tumors, suggesting therapy-related selection of a transcriptional subtype with characteristics unfavorable for therapy. We conclude that therapy decisions should be based on genetic and transcriptional characteristics of recurrences rather than primary tumors to enable optimally tailored treatment strategies.

DNA methylation-based classification of sinonasal tumors.

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs.

miRNA expression profiling in formalin-fixed and paraffin-embedded placental tissue samples from pregnancies with severe preeclampsia.

AIMS: Micro RNAs (miRNAs) are small, single-strand RNAs, playing an important role in post-transcriptional gene regulation. The placenta is considered to play a key role in pathogenesis of preeclampsia. The purpose of this study was to demonstrate deregulation of miRNAs in placentas with preeclampsia using formalin-fixed and paraffin-embedded (FFPE) tissues. METHODS: Expression levels of 162 miRNAs were measured in FFPE placental tissues (5 with severe preeclampsia, 5 from a control group) using a quantitative qPCR based technique. RESULTS: Six miRNAs were more than 2-fold over-expressed in severe preeclampsia: let-7b, miRNA-302*, miRNA-104, miRNA-128a, miRNA-182* and miRNA-133b. Gene ontology analyses were performed using the algorithms "TargetScanS", "microRNA", and "PicTar". CONCLUSIONS: Two of the up-regulated miRNAs (miRNA-182* and miRNA-133b) are putative regulators of the transcript variants 1 and 2 of the BCL2-like gene, which controls apoptosis. miRNA-182* is also a probable angiogenesis regulator via angiogenin and VEGF-B. Apoptosis and angiogenesis are major mechanisms presumed to be involved in the pathogenesis of preeclampsia. Moreover, usability of qPCR technique based miRNA profiling for FFPE tissues was proofed. Hence FFPE tissue is the most widely used material for retrospective clinical studies, this method has a great property for future investigations in placenta research.

First approach to distinguish between cardiac and arteriosclerotic emboli of individual stroke patients applying the histological THROMBEX-classification rule.

Endovascular treatment of strokes caused by large vessel occlusion enables the histopathological investigation of the retrieved embolus, possibly providing a novel opportunity to contribute to the diagnostic workup of etiology and to define secondary prevention measures in strokes with uncertain genesis. We aimed to develop a classification rule based on pathophysiological considerations and adjustment to reference thrombi for distinction between cardiac and arteriosclerotic emboli and to validate this classification rule on a patient cohort. From 125 patients with stroke due to large vessel occlusion and thrombectomy, 82 patients with known etiology (55 cardioembolic and 27 arterioembolic strokes) were included. The corresponding emboli were histologically evaluated by two raters blinded to the etiology of stroke by means of a novel classification rule. Presumed etiology and classification results were compared. Agreement concerning cardiac emboli was 72.2% (95% CI: 58.4-83.5) for rater I and 78.2% (95% CI: 65.0-88.2) for rater II. Agreement concerning arteriosclerotic emboli was 70.4% (95% CI: 49.8-86.3) for rater I and 74.1% (95% CI: 53.7-88.9) for rater II. Overall agreement reached 71.6% (95% CI: 60.5-81.1) for rater I and 76.8% (95% CI: 66.2-85.4) for rater II. Within the limits of generally restricted accuracy of histological evaluations, the classification rule differentiates between cardiac and arteriosclerotic emboli of acute ischemic stroke patients. Further improvement is needed to provide valuable complementary data for stroke etiology workup.

A New Survival Score for Patients Scheduled for Palliative Irradiation of Locally Advanced Carcinoma of the Head-and-Neck.

BACKGROUND/AIM: Patients with advanced squamous cell carcinoma of the head-and-neck (SCCHN) may be assigned to palliative irradiation. A survival score was developed for this group to support treatment personalization. PATIENTS AND METHODS: Seventy-eight patients who received palliative irradiation for SCCHN and had complete data regarding performance score, pre-radiotherapy hemoglobin levels, and main tumor site were included in this retrospective study. Six-month survival rates of these factors were divided by 10 (factor scores) and added for each patient (total patient scores). RESULTS: Total patient scores ranged between 8 and 15 points. Three groups were designed based on the 6-month survival rates, namely 8-9 (n=15), 11-13 (n=36), and 14-15 (n=27) points. Six-month survival rates were 13%, 28%, and 63%, and median survival times were 1, 2, and 11 months (p=0.001). CONCLUSION: A new survival score including three prognostic groups was developed. This new tool can help physicians when designing personalized treatments for patients with SCCHN scheduled for palliative irradiation.

Palliative Local Radiotherapy for Advanced Squamous Cell Carcinoma of the Head-and-Neck: Prognostic Factors of Survival.

BACKGROUND/AIM: A considerable number of patients with advanced head-and-neck cancer (SCCHN) receive palliative radiotherapy. This study aimed to identify prognostic factors for survival to facilitate personalized treatment for these patients. PATIENTS AND METHODS: Ninety-two patients receiving palliative radiotherapy for SCCHN were retrospectively analyzed. Fourteen characteristics were evaluated for survival including age, gender, performance score, pre-radiotherapy hemoglobin, tumor site and stage, histologic grade, p16-status, equivalent dose in 2 Gy-fractions (EQD2), completion of radiotherapy, upfront surgery and systemic therapy. RESULTS: On univariate analysis, improved survival was significantly associated with pre-radiotherapy hemoglobin ≥12 g/dl (p=0.003), EQD2 >42.3 Gy (p=0.003) and completion of radiotherapy (p<0.001). In the multivariate analysis, hemoglobin levels remained significant (p=0.024). Trends were found for EQD2 (p=0.057) and completion of radiotherapy (p=0.093). CONCLUSION: Prognostic factors for survival were identified that can facilitate treatment personalization. The fact that higher EQD2 and completion of radiotherapy were associated with improved survival demonstrates the importance of close monitoring and care of these patients during radiotherapy.