Survival In Head And Neck Cancer Patients Research Articles

Positive correlation between persistence of medical nutrition therapy and overall survival in patients with head and neck cancer.

Background: Several factors can affect overall survival of head and neck cancer (HNC) patients, including characteristics of the cancer disease and response to treatments. However, patients' nutritional status and the effectiveness of medical nutrition therapy (MNT) can also impact overall survival. The primary goal of our research was to collect real-life data on the use of MNT in HNC patients and to specifically investigate the correlation between survival and the duration of uninterrupted (persistent) nutrition. Method: The data of this retrospective, analytical, cohort study was collected from electronic healthcare records from the Hungarian National Health Insurance Fund Management. Overall, 38,675 HNC patients' data of the period between 2012 and 2021 was used. We applied multi-step exclusions to identify patient groups accurately and to avoid biasing factors. Statistical analysis was done by the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: Throughout the investigated period 16,871 (64%) patients received MNT therapy out of 26,253 newly diagnosed patients (≥18years). In terms of the persistence of MNT, we divided the patients into three groups (1-3; 4-6; ≥7-month duration of MNT). When comparing these groups, we found that patients receiving long-term (≥7months) MNT had a significantly longer overall survival (p < 0.0001) than those who received MNT for a shorter duration, both in locally advanced and recurrent/metastatic cases. Conclusion: The main outcome of the study is that there is a positive correlation between the persistence of MNT and the overall survival in HNC patients when nutritional intervention lasts several months. It highlights the responsibility of the specialists during the patient journey to use MNT early and to continue its use for as long as it is beneficial to the patients.

Development and validation of survival prognostic models for head and neck cancer patients using machine learning and dosiomics and CT radiomics features: a multicentric study

BackgroundThis study aimed to investigate the value of clinical, radiomic features extracted from gross tumor volumes (GTVs) delineated on CT images, dose distributions (Dosiomics), and fusion of CT and dose distributions to predict outcomes in head and neck cancer (HNC) patients.MethodsA cohort of 240 HNC patients from five different centers was obtained from The Cancer Imaging Archive. Seven strategies, including four non-fusion (Clinical, CT, Dose, DualCT-Dose), and three fusion algorithms (latent low-rank representation referred (LLRR),Wavelet, weighted least square (WLS)) were applied. The fusion algorithms were used to fuse the pre-treatment CT images and 3-dimensional dose maps. Overall, 215 radiomics and Dosiomics features were extracted from the GTVs, alongside with seven clinical features incorporated. Five feature selection (FS) methods in combination with six machine learning (ML) models were implemented. The performance of the models was quantified using the concordance index (CI) in one-center-leave-out 5-fold cross-validation for overall survival (OS) prediction considering the time-to-event.ResultsThe mean CI and Kaplan-Meier curves were used for further comparisons. The CoxBoost ML model using the Minimal Depth (MD) FS method and the glmnet model using the Variable hunting (VH) FS method showed the best performance with CI = 0.73 ± 0.15 for features extracted from LLRR fused images. In addition, both glmnet-Cindex and Coxph-Cindex classifiers achieved a CI of 0.72 ± 0.14 by employing the dose images (+ incorporated clinical features) only.ConclusionOur results demonstrated that clinical features, Dosiomics and fusion of dose and CT images by specific ML-FS models could predict the overall survival of HNC patients with acceptable accuracy. Besides, the performance of ML methods among the three different strategies was almost comparable.

Clinical Review on Head and Neck CBCT Images

Optimal quality assurance is vital in head and neck (HN) radiotherapy (RT), as inferior dosimetry has proven to compromise survival in HN cancer patients. Image guidance using cone-beam computed tomography (CBCT) has enabled precise matching of tumor targets. The objective was to analyze the translational and rotational shifts obtained from HN CBCT in order to develop the 6D HN imaging protocol, henceforth to achieve the best precision radiotherapy. Sixty patients who received treatment from January 2021 to September 2022 were randomly selected - 10 from each sub-site (paranasal sinuses, nasopharynx, oropharynx, oral cavity, larynx-hypopharynx-thyroid and early-stage glottis). Weekly CBCT obtained were analyzed using offline automatic image registration (IR) on an electronic patient information management system. First, 2 regions of interests (ROIs) were defined; one was based on departmental HN IGRT protocol and the other covered the entire planning target volume (PTV). Subsequently, IR was performed with 2 different algorithms; Maximum Mutual Information (MMI) (soft tissue-based) and Chamfer (bone-based). Each CBCT was inspected manually by an individual to avoid inter-observer variability. The shifts were reported as mean ± standard deviation (SD). Paired t-test was used to analyze the variances in translational and rotational displacements between the different ROIs and algorithm. Early-stage glottis was excluded in the ROI comparison as the treatment field was small and the ROI covered the entire PTV. Overall setup errors were 1.2 ± 1.1mm for the translational shifts and 0.7 ± 0.6° for the rotational. The overall frequency of displacement was 95.2% ≤2° and 99.5% ≤5mm. MMI was more constant than Chamfer for HN CBCT matching as reflected by a considerably smaller translational (1.09 ± 1.05mm vs 1.26 ± 1.16mm, p<0.001) and rotational (0.67 ± 0.57° vs 0.77 ± 0.70°, p<0.001) shifts. The comparison of defining ROIs (PTV vs Protocol) was insignificant in the translational shifts (p = 0.057). However, a substantial difference was observed in the rotational displacements (p = 0.003). The analysis was fundamental in identifying the optimal matching tool and it supports the HN 6D imaging protocol. This audit validated the current 5mm tolerance for translational shift and further established a 2° tolerance for the rotational shift for HN 6D CBCT matching. Profoundly, soft tissue localization is of the utmost importance for highly conformal modulated RT, and adaptation of soft tissue matching is strongly encouraged for HN tumors located in these regions.

Inter-hospital variation in data collection, radiotherapy treatment, and survival in patients with head and neck cancer: A multisite study

Background and purposeInter-hospital inequalities in head and neck cancer (HNC) survival may exist due to variation in radiotherapy treatment-related factors. This study investigated inter-hospital variation in data collection, primary radiotherapy treatment, and survival in HNC patients from an Australian setting. Materials and methodsData collected in oncology information systems (OIS) from seven Australian hospitals was extracted for 3,182 adults treated with curative radiotherapy, with or without surgery or chemotherapy, for primary, non-metastatic squamous cell carcinoma of the head and neck (2000–2017). Death data was sourced from the National Death Index using record linkage. Multivariable Cox regression was used to assess the association between survival and hospital. ResultsInter-hospital variation in data collection, primary radiotherapy dose, and five-year HNC-related death was detected. Completion of eleven fields ranged from 66%-98%. Primary radiotherapy treated Tis-T1N0 glottic and any stage oral cavity and oropharynx cancers received significantly different time-corrected biologically equivalent dose in two gray fractions (EQD2T) by hospital, with observed deviation from Australian radiotherapy guidelines. Increased EQD2T dose was associated with a reduced risk of five-year HNC-related death in all patients and those treated with primary radiotherapy. Hospital, tumour site, and T and N classification were also identified as independent prognostic factors for five-year HNC-related death in all patients treated with radiotherapy. ConclusionUnexplained variation exists in HNC-related death in patients treated at Australian hospitals. Available routinely collected data in OIS are insufficient to explain variation in survival. Innovative data collection, extraction, and classification practices are needed to inform clinical practice.

Integrated Multi-Omics Signature Predicts Survival in Head and Neck Cancer.

Head and Neck Cancer (HNC) is characterized by phenotypic, biological, and clinical heterogeneity. Despite treatment modalities, approximately half of all patients will die of the disease. Several molecular biomarkers have been investigated, but until now, without clinical translation. Here, we identified an integrative nine-gene multi-omics signature correlated with HNC patients’ survival independently of relapses or metastasis development. This prognosis multi-omic signature comprises genes mapped in the chromosomes 1q, 3p, 8q, 17q, 19p, and 19q and encompasses alterations at copy number, gene expression, and methylation. Copy number alterations in LMCD1-A1S and GRM7, the methylation status of CEACAM19, KRT17, and ST18, and the expression profile of RPL29, UBA7, FCGR2C, and RPSAP58 can predict the HNC patients’ survival. The difference higher than two years observed in the survival of HNC patients that harbor this nine-gene multi-omics signature can represent a significant step forward to improve patients’ management and guide new therapeutic targets development.

Комбинированное действие хронического ионизирующего излучения и многократного лазерного воздействия на когнитивные функции крыс

Low-level laser therapy (LLLT) may have utility in the management of side effects of radiation therapy in head and neck cancer (HNC) patients. Although evidence suggests that LLLT is safe treatment for HNC patients, more research is imperative and vigilance remains warranted to de-tect any potential adverse effects of LLLT on treatment outcomes and survival of HNC patients. The purpose of this study was to evaluate the effect of transcranial low-level laser irradiation (LLLI) in combined with whole-body ionizing radiation (IR) on conditioned-reflex activity of rats. Seventy healthy Wistar female rats were distributed into the following groups: Group 1, sham control; Group 2, LLLI; Group 3, IR; Group 4, IR and LLLI. Group 3 and Group 4 chronically ex-posed to IR (30 days; 5,3+/-0,5 mGy/h; 3,7 Gy). Group 2 and Group 4 received five applications of LLLI, once a day for 15 min (wavelength 890 nm, the pulse duration was 100 ns, impulse fre-quency 10000 Hz, output power – 1,7 mW). Cognitive functions of the rats were tested using shut-tle-box avoidance method. The rats were tested 30 minutes later, 24 hours later, and 14 days af-ter the end of LLLI. LLLI and IR in isolated action (groups 2 and 3) did not significantly affect the conditioned reflex activity of rats. The negative effect of combined exposure to these factors (group 4) on the development and reproduction of an active avoidance reflex within 24 hours af-ter exposure was revealed. Gradually this negative effect weakened and within two weeks was leveled. Thus, the combined action of IR and LLLI may pose a potential danger to the cognitive function of the brain.

Effects of nutrition impact symptoms before radiotherapy on overall survival in patients with head and neck cancer: a prospective cohort study

Rationale: Nutrition impact symptoms (NISs) effect patients’ dietary intake or digestive absorption and have a negative impact on their nutritional status. The NISs are common in head and neck cancer (HNC) patients as a result of tumor location and treatment received. This study aimed to explore the effects of NISs before radiotherapy on overall survival in HNC patients.

Systematic Analysis and Identification of Dysregulated Panel lncRNAs Contributing to Poor Prognosis in Head-Neck Cancer.

Head and neck cancer (HNC) is one of the most prevalent cancers worldwide, accounting for approximately 5% of all cancers. While the underlying molecules and their pathogenetic mechanisms in HNC have yet to be well elucidated, recent studies have shown that dysregulation of lncRNAs may disrupt the homeostasis of various biological pathways. However, the understanding of lncRNAs in HNC is still limited by the lack of expression profiling. In the present study, we employed a systematic strategy to identify a panel of lncRNA associated with HNC. A cancer-related lncRNA profile PCR array was screened to explore potential molecules specific for HNC. A total of 55 lncRNAs were found to be dysregulated in HNC cells when compared to normal keratinocytes. Further analysis of the prognostic significance using The Cancer Genome Atlas (TCGA) database revealed 15 lncRNAs highly correlated with overall survival in HNC patients. Additionally, clinical sample expression analysis of the TCGA-HNSC cohort revealed 16 highly dysregulated lncRNAs in HNC, resulting in a combined 31-lncRNA signature panel that could predict prognosis. Validation of these molecules confirmed the considerable level of altered expressions in HNC cells, with XIST, HOXA11-AS, TSIX, MALAT1, WT1-AS, and IPW being the most prominently dysregulated. We further selected a molecule from our panel (XIST) to confirm the validity of these lncRNAs in the regulation of cancer aggressiveness. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses demonstrated that XIST participated in various cancer-related functions, including cell proliferation and metastasis. XIST silencing with the RNAi technique substantially reduced invasion and migration in several HNC cell lines. Thus, our study defined a 31-lncRNA panel as prognostic signatures in HNC. These perspective results provide a knowledge foundation for further application of these molecules in precision medicine.

Association of pretreatment financial toxicity with time to treatment for patients with head and neck carcinoma and lung carcinoma.

131 Background: Financial toxicity (FT) describes objective and subjective burden of costs associated with medical care. Patients with head and neck cancer (HNC) and lung carcinoma are acutely impacted by FT, as these cancers disproportionately occur in populations that are poor, unemployed, and/or of minority backgrounds compared to patients with other cancers. Our group recently published results showing delay in time to treatment initiation (TTI) was associated with poorer survival in HNC patients. Another study reported that FT was associated with worse progression-free survival in non-small cell lung cancer patients. In this study, we sought to investigate the association between FT, TTI and clinical outcomes among HNC and lung carcinoma patients, as well as predictors of FT. Methods: A retrospective analysis of 140 patients diagnosed with either HNC or lung carcinoma between January 2007 and March 2018 with quality-of-life data collected prospectively at the time of radiation oncology treatment was conducted. Participants responded to a question about their experience on ‘financial difficulties’ with a 4-point Likert Scale within the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) quality of life assessment. FT was low when patients indicated ‘1’ (not at all) or ‘2’ (a little), and high if patients indicated ‘3’ (quite a bit), and ‘4’ (very much). Chi-square test and Student’s t-test were used to compare characteristics of patients with and without FT. The association between FT and TTI and survival outcomes were analyzed using the Kaplan-Meier methods and Cox proportional-hazards regression models. Results: The study sample included 70 patients with HNC (mean [SD] age, 64.3 [12.0]; 62.7% male) and 70 patients with lung carcinoma (mean [SD] age, 69.1 [10.2]; 38.0% male). Over half (N = 80, 55.2%) reported experiencing financial toxicity (64% HNC vs. 45.7% lung carcinoma). Younger age (&lt; 60 years), having Medicaid, and having small-cell lung carcinoma were associated with greater FT (p = 0.049, p = 0.042, p = 0.034, respectively). Patients who reported having poorer health and quality of life also experienced greater FT (p = 0.030, p = 0.016, respectively). HNC patients who experienced greater FT were less likely to experience treatment delay (p = 0.035). After adjusting for age, sex, ethnicity, tumor site, and tumor stage, FT was associated with worse survival outcomes in all patients (HR = 1.52, 95% CI 1.06-2.19). Conclusions: Greater FT was associated with younger age, having Medicaid, and having small-cell lung carcinoma. HNC patients who experienced greater FT were less likely to experience treatment delay, which suggests that delay may not be a causative factor for the worsened survival seen with patients who report FT.

The Clinical Characteristics and Prognostic Nomogram for Head and Neck Cancer Patients with Bone Metastasis.

Background Head and neck cancer (HNC) is the sixth most common malignancy globally, and many demographics and clinicopathological factors influence its prognosis. This study aimed to construct and validate a prognostic nomogram to predict the prognosis of HNC patients with bone metastasis (BM). Methods A total of 326 patients with BM from HNC were collected from the SEER database as the subjects of this study. In a ratio of 7 to 3, patients were randomly divided into training and validation groups. Independent prognostic factors for HNC patients with BM were identified by univariate and multivariate Cox regression analysis. The nomogram for predicting the prognosis was constructed, and the model was evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis. Result The independent prognostic factors for HNC patients with BM included age, primary site, lung metastasis, and chemotherapy. The area under the curve predicting overall survival at 12, 24, and 36 months was 0.768, 0.747, and 0.723 in the training group and 0.729, 0.723, and 0.669 in the validation group, respectively. The calibration curves showed good agreement between the predicted and actual values for overall survival. In addition, the decision curve analysis showed that this prognostic nomogram model has a high clinical application. Conclusion This study developed and validated a nomogram to predict overall survival in HNC patients with BM. The prognostic nomogram has high accuracy and utility to inform survival estimation and individualized treatment decisions.

A national cancer database analysis on stereotactic body radiation therapy of head and neck cancers

BackgroundTo evaluate demographic, clinicopathological, treatment factors including biological effective radiation dose (BED) that influence overall survival in head and neck cancer (HNC) patients treated with stereotactic body radiation therapy (SBRT). MethodsBetween 2004 and 2015, 591 SBRT-treated HNC patients were identified from the National Cancer Data Base. A BED using an alpha/beta ratio of 10 (BED10), was used to compare dose fractionation of different SBRT regimens. Overall survival was estimated using the Kaplan Meier method, and log-rank tests were used to determine statistical significance. Cox regression modeling was used to compute crude and adjusted hazard ratios (HR) with 95% confidence intervals (CI). ResultsMedian follow-up was 11.9 (interquartile range, 5.5 to 26.7) months. The 5-year overall survival rate was 15.5%. On multivariate analysis, older age, Charlson-Deyo comorbidity score ≥ 1, history of cancer, tumor, nodal and metastatic stage, and receiving treatment at academic/research program were associated with poor survival. Compared to SBRT alone, superior survival was observed with SBRT with chemotherapy, surgery with SBRT, but not surgery with SBRT and chemotherapy. Improved survival was observed with aa BED10 of ≥59.5 Gy (adjusted HR 0.57, 95% CI 0.46–0.70, P < 0.0001). ConclusionsFactors affecting associated with worse survival in HNC patients treated with SBRT included older age, patient comorbidities, advanced tumor stage, cancer history, and lower biological effective SBRT dose. Level of evidence2b (individual cohort study).

Clinical features of head and neck cancer patients with brain metastases: A retrospective study of 88 cases.

Brain metastases (BM) arising from head and neck cancer (HNC) are rare and not well characterized. This study aims to describe the clinicopathological features, treatments, prognostic factors, and survival in HNC patients with BM. Non-thyroid HNC patients referred to BC Cancer from 1998 to 2016 were retrospectively reviewed for BM. The Kaplan-Meier method, log-rank test, and Cox regression analysis were used to assess post-BM survival and prognostic factors. Out of 9432 HNC patients, 88 patients developed BM (0.9%, median follow-up 3.4years). On average, the BM were diagnosed 18.5months after the primary diagnosis and tended to arise after distant metastases to extracranial sites (85%) such as the lungs (78%). At BM presentation, 84% were symptomatic and two thirds had a poor performance status (ECOG≥2, 68%). The median post-BM survival was 2.5months (95% CI 2.1-3.3months). On multivariable analysis, management of BM with radiotherapy (RT) alone (3.3months, 95% CI 2.3-4.6, p=0.005) and RT with surgery (4.4months, 95% CI 2.8-6.9, p<0.001) was associated with longer survival compared to best supportive care alone (1.4months, 95% CI 1.0-2.0months). Age, sex, performance status, sub-localization of the primary HNC, presence of extracranial metastases, and number of intracranial metastases were not associated with post-BM survival (all p≥0.05). This is the largest study to date in BM from HNC. BM occur late in the course of HNC and carry a poor prognosis. Treatment with intracranial radiotherapy both with and without surgery was associated with improved survival.

Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis.

Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are still unknown. In this study, human normal oral epithelial (HNOE) cells, NanoString PanCancer Pathways panel of 770 gene transcripts and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were applied to discover differentially expressed genes (DEG) modulated by WPS. In silico analysis was performed to analyze the impact of these genes in HN cancer patient’s biology and outcome. We found that WPS can induce the epithelial–mesenchymal transition (EMT: hallmark of cancer progression) of HNOE cells. More significantly, our analysis of NanoString revealed 23 genes deregulated under the effect of WPS, responsible for the modulation of cell cycle, proliferation, migration/invasion, apoptosis, signal transduction, and inflammatory response. Further analysis was performed using qRT-PCR of HNOE WPS-exposed and unexposed cells supported the reliability of our NanoString data. Moreover, we demonstrate those DEG to be upregulated in cancer compared with normal tissue. Using the Kaplan–Meier analysis, we observed a significant association between WPS-deregulated genes and relapse-free survival/overall survival in HN cancer patients. Our findings imply that WPS can modulate EMT as well as a set of genes that are directly involved in human HN carcinogenesis, thereby affecting HN cancer patients’ survival.

Analysis of Stereotactic Body Radiotherapy for Head and Neck Cancer using the National Cancer Database

Recent studies have demonstrated promising results with stereotactic body radiation therapy (SBRT), usually as re-irradiation in recurrent head and neck cancer (HNC) or second primary HNC, and in patients who cannot tolerate 6-7 weeks of conventional radiotherapy. We seek to evaluate the uptake of SBRT for HNC using the National Cancer Database (NCDB) and evaluate social, clinicopathological and treatment factors impacting overall survival (OS). To evaluate the national utilization of SBRT for head and neck cancer and investigate the relationship between social demographics, clinicopathological factors, and treatment dose fractionation with overall survival. The NCDB was queried to identify 549 HNC cases undergoing SBRT from 2004 to 2015. Patients were treated in 1 (15-24Gy, n=46), 2 (7.5-12Gy, n=19), 3 (5-12Gy, n=57), 4 (5-12Gy, n=34), or 5 (4-10Gy, n=393) fractions. The biologically effective dose with α/β=10 (BED10) was calculated. A BED10 of 59.5 Gy10 using a dose/fractionation scheme of 35 Gy in 5 fractions was used as a cut point to evaluate SBRT effective dose regimens on survival. The following patient factors were analyzed: age, race, insurance status, median household income, and Charlson-Deyo Score (CDS), year of diagnosis, TNM stage category, history of cancer, and tumor site (larynx/hypopharynx, oral cavity/oropharynx/lip, sino-nasal/nasopharynx, salivary gland). Treatment factors included BED10 (<59.5 Gy10, ≥59.5 Gy10), facility type, and treatment modality (radiation only, RT; chemoradiation, CRT; surgery with radiation, S+R; surgery with chemoradiation, S+CRT). Median OS, three, and five-year survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards regression modeling was used to compute adjusted hazard ratios (HR) with 95% confidence intervals (CI). The median age was 70 years (interquartile range, 60-81). The majority of patients were white (84.7%, n=465), on Medicare (56.5%, n=310), and were treated at an academic treatment facility (63.2%, n=347). History of prior cancer was recorded in 39.3% of patients. The most common treatment modality was RT (43.5%, n=239) followed by CRT (24.6%, n=135), S+R (24.0%, n=134), and S+CRT (7.8%, n=43). Median follow-up in all and surviving patients was 11.9 and 29 months, respectively. A total of 436 deaths were reported, and the overall 3-year survival rate was 23.0% (median survival, 12.6 months). On multivariate analysis, older age, CDS ≥2, advancing T, and N category was associated with poor survival. Patients with a history of cancer (HR 1.40, 95% CI 1.13-1.75, p=0.003) and M1 disease (HR 2.34, 95% CI 1.73-3.15, p<0.0001) also reported poor survival. Compared to RT, improved survival was noted for CRT (HR 0.61, 95% CI 0.47-0.80, p=0.0003) and S+R (HR 0.50, 95% CI 0.37-0.69, p<0.0001) but not S+CRT. A BED10 value of ≥59.5 Gy10 was also associated with improved survival (HR 0.57, 95% CI 0.46-0.71, p<0.0001). No significant difference in survival was noted by race, insurance, income, and treatment facility. Factors adversely affecting survival in HNC patients treated with SBRT included a history of prior cancer, older age, patient co-morbidities, advanced T, N, and M stage. SBRT dose fractionation with a BED10 of ≥59.5 Gy, and combination with chemotherapy and surgery improves survival for HNC.

Risk factors for aspiration pneumonia during concurrent chemoradiotherapy or bio-radiotherapy for head and neck cancer

BackgroundAspiration pneumonia is one of the most important side effects of chemoradiotherapy (CRT) and bio-radiotherapy (BRT) in patients with head and neck cancer (HNC). Aspiration pneumonia can lead to cancer-related mortality in HNC patients. However, the relationship between aspiration pneumonia occurring during CRT or BRT for HNC and treatment outcomes in HNC patients is not well characterized. In this study, we assessed the influence of aspiration pneumonia on treatment outcomes and sought to identify the clinical risk factors for aspiration pneumonia during definitive CRT and BRT in HNC patients.MethodsWe retrospectively assessed the data pertaining to patients with locally advanced HNC who received definitive CRT or BRT at the Shizuoka Cancer Center between August 2006 and December 2016.ResultsAmong the 374 HNC patients who received CRT or BRT, 95 (25.4%) developed aspiration pneumonia during treatment. Aspiration pneumonia was significantly associated with therapeutic response to CRT or BRT (multivariate adjusted odds ratio for complete response, 0.52, p = 0.020) and poor overall survival (multivariate adjusted hazard ratio for overall survival, 1.58, p = 0.024). The multivariate analyses identified four independent factors for aspiration pneumonia: poor oral hygiene, high N-classification, hypoalbuminemia before treatment, and inpatient treatment.ConclusionsAspiration pneumonia occurring during CRT or BRT has a detrimental effect on the therapeutic response and survival of HNC patients. Careful attention should be paid to these risk factors for aspiration pneumonia in HNC patients undergoing CRT or BRT.

Oral hygiene and the overall survival of head and neck cancer patients.

Poor oral hygiene is an established risk factor of head and neck cancer (HNC); however, its role in the survival of HNC patients is unclear. This study evaluated the association between oral hygiene habits, including regular dental visits, frequency of tooth brushing, and use of dental floss, and the overall survival (OS) of HNC patients using interview data collected from 740 HNC patients. In addition, the interactions between oral hygiene and the polymorphisms of TLR2 and TLR4 on the OS of HNC patients were assessed. The analysis indicated that poor oral hygiene was significantly associated with poorer OS of HNC patients (hazard ratio (HR) = 1.38, 95% confidence interval (CI): 1.03‐1.86). This association was modified by a single nucleotide polymorphism, rs11536889, of TLR4. A significant association between poor oral hygiene and worse survival of HNC was observed among those with the CG or CC genotype (HR = 2.32, 95% CI: 1.41‐3.82) but not among those with the GG genotype (HR = 0.95, 95% CI: 0.65‐1.40). Our results suggested that poor oral hygiene is not only a risk factor but may also be a prognostic factor of HNC.

Prognostic signature associated with radioresistance in head and neck cancer via transcriptomic and bioinformatic analyses

BackgroundRadiotherapy is an indispensable treatment modality in head and neck cancer (HNC), while radioresistance is the major cause of treatment failure. The aim of this study is to identify a prognostic molecular signature associated with radio-resistance in HNC for further clinical applications.MethodsAffymetrix cDNA microarrays were used to globally survey different transcriptomes between HNC cell lines and isogenic radioresistant sublines. The KEGG and Partek bioinformatic analytical methods were used to assess functional pathways associated with radioresistance. The SurvExpress web tool was applied to study the clinical association between gene expression profiles and patient survival using The Cancer Genome Atlas (TCGA)-head and neck squamous cell carcinoma (HNSCC) dataset (n = 283). The Kaplan-Meier survival analyses were further validated after retrieving clinical data from the TCGA-HNSCC dataset (n = 502) via the Genomic Data Commons (GDC)-Data-Portal of National Cancer Institute. A panel maker molecule was generated to assess the efficacy of prognostic prediction for radiotherapy in HNC patients.ResultsIn total, the expression of 255 molecules was found to be significantly altered in the radioresistant cell sublines, with 155 molecules up-regulated 100 down-regulated. Four core functional pathways were identified to enrich the up-regulated genes and were significantly associated with a worse prognosis in HNC patients, as the modulation of cellular focal adhesion, the PI3K-Akt signaling pathway, the HIF-1 signaling pathway, and the regulation of stem cell pluripotency. Total of 16 up-regulated genes in the 4 core pathways were defined, and 11 over-expressed molecules showed correlated with poor survival (TCGA-HNSCC dataset, n = 283). Among these, 4 molecules were independently validated as key molecules associated with poor survival in HNC patients receiving radiotherapy (TCGA-HNSCC dataset, n = 502), as IGF1R (p = 0.0454, HR = 1.43), LAMC2 (p = 0.0235, HR = 1.50), ITGB1 (p = 0.0336, HR = 1.46), and IL-6 (p = 0.0033, HR = 1.68). Furthermore, the combined use of these 4 markers product an excellent result to predict worse radiotherapeutic outcome in HNC (p < 0.0001, HR = 2.44).ConclusionsFour core functional pathways and 4 key molecular markers significantly contributed to radioresistance in HNC. These molecular signatures may be used as a predictive biomarker panel, which can be further applied in personalized radiotherapy or as radio-sensitizing targets to treat refractory HNC.

Interleukin 17 and peripheral IL-17-expressing T cells are negatively correlated with the overall survival of head and neck cancer patients.

The presence and clinical significance of interleukin (IL)-17 and IL-17-expressing cells have recently been studied in several types of cancer, but their correlation to tumor development remains controversial. Additionally, the contribution of peripheral IL-17-expressing cells to head and neck cancer (HNC) progression is still poorly understood. We collected peripheral blood from healthy donors and HNC patients to isolate PBMCs. The percentages of IL-17-expressing cells and the production of inflammatory cytokines in PBMCs were measured to determine their association with clinical outcomes and overall survival in HNC. We evaluated the effect and potential mechanism of IL-17 on human oral squamous carcinomas in vitro using exogenous IL-17 stimulation. In comparison to healthy donors, the PBMCs of HNC patients have a significant accumulation of IL-17-expressing T cells and their frequencies were positively correlated with the disease stage. A significantly higher production of PBMC IL-17, TGF-β and IL-21 and plasma VEGF-A were found in HNC patients. Importantly, the 5-years overall survival of HNC patients with a higher percentage of IL-17-expressing cells is significantly decreased. Furthermore, the addition of IL-17 appeared to promote human oral squamous carcinoma cell proliferation via the production of IL-6 and VEGF-A. Our findings suggest that IL-17 has the potential to mediate pro-tumor immunity in the HNC tumor microenvironment. Enhanced IL-17-expressing cells, including Th17 and Tc17 cells, in the peripheral blood could be a significant predictor of a poor prognosis for HNC patients.

Esophageal squamous cell neoplasia is an independent negative prognostic factor for head and neck cancer patients.

Patients with head and neck cancer (HNC) have a high incidence of esophageal squamous cell neoplasms (ESCN). ESCN also has a negative impact on the survival of HNC patients. However, recent endoscopic advances enable the early detection of ESCN, and novel treatments may lead to improving survival rates for HNC patients with ESCN. HNC patients who underwent magnifying esophagogastroduodenoscopy (EGDS) from 2005 to 2012 were included in this study (n = 226). We analyzed the prevalence and prognostic value of ESCN in HNC patients and the difference in overall survival between HNC patients with and without ESCN. Thirty-four patients (15%) developed an ESCN during their clinical course. Of the 34 patients, 10 patients underwent endoscopic resection for ESCN and 10 patients underwent simultaneous chemoradiation therapy for HNC and ESCN. The 3-year survival rates in HNC patients with and without ESCN were 53% and 70%, respectively. Multivariate analysis identified the advanced clinical stage of the HNC [hazard ratio (HR) = 2.15; 95% confidence interval (CI) = 1.18-3.93; p = 0.012] and the presence of ESCN (HR = 1.73; 95% CI = 1.00-2.97; p = 0.049) as significant and independent determinants of overall survival. Our study suggests that although the survival of HNC patients with ESCN may be improved by routine EGDS during tumor surveys and by advances in endoscopy, the presence of ESCN still remains an independent negative prognostic factor for HNC patients.

MTOR PATHWAY PROTEIN IMMUNOEXPRESSION AS A PROGNOSTIC FACTOR FOR SURVIVAL IN HNC: A SYSTEMATIC REVIEW AND META-ANALYSIS

Activated proteins in the mTOR pathway are deregulated in multiple types of cancer. These proteins may be important targets for anticancer therapy. The aim of this study was to summarize existing cohort studies to determine whether immunoexpression of mTOR pathway proteins are important prognostic factors for survival in head and neck cancer (HNC) patients. A systematic review was performed using the Cochrane, Lilacs, PubMed, ScienceDirect, Scopus and Web of Science databases (up to 23 January 2015). A meta-analysis was conducted to measure the frequency of protein expression in HNC patient samples and the prognostic value of mTOR pathway proteins for overall survival (OS) and disease-free survival (DFS). 12 studies were included in the final analysis. The meta-analysis revealed that the frequency of overall expression of mTOR pathway proteins was 74.42% (CI: 63.3 to 84.0, P < 0,001, n=2,016 samples). The survival meta-analysis showed a pooled hazard ratio for OS and DFS of 1.44 (95% confidence interval [95% CI] 1.14-1.73) and 1.18 (95% CI 0.71-1.64), respectively. This systematic review and meta-analysis support evidence that mTOR pathway proteins can be used as predictive markers for survival in HNC patients because their expression was significantly associated with poor OS and short DFS.