头颈部放疗患者口腔假丝酵母菌感染的快速检测

目的通过对传统培养法和PCR法在假丝酵母菌感染检出率的比较,拟探索一种能够早期、快速、高效检测头颈部放疗患者假丝酵母菌感染的方法。方法收集120名头颈部放疗患者唾液,分别应用假丝酵母菌显色培养基（CHROMagar）进行分离、培养和鉴定;同时提取基因组DNA,通过假丝酵母菌通用引物、特异性引物、改良引物进行PCR扩增,结果与假丝酵母菌表型进行对比。结果与传统培养法相比,PCR法检出率更高（χ2=47.672,P=0.000）;改良特异性引物D扩增的检出率为77%,高于通用引物B（χ2=7.702,P=0.006）和特异性引物C（χ2=12.522,P=0.001）。结论本研究证实PCR技术耗时短,阳性检出率高,可用于头颈部肿瘤放疗患者假丝酵母菌感染的快速检测。     

Smoking during radiotherapy for head and neck cancer and acute mucosal reaction

AimWe compared the incidence of RTOG/EORTC grade III and higher acute mucositis in patients with head and neck cancer who continued to smoke during radiotherapy with those who quit smoking.BackgroundThere are conflicting data on the relationship between smoking during radiotherapy and the severity of acute mucosal reaction. More studies dealing with this issue are needed.Materials and methodsAmong 136 patients receiving curative radio(chemo)therapy, 37 (27%) declared that they had not quit smoking during radiotherapy. The intensity of mucositis was scored daily by a nurse and weekly by a physician using the RTOG/EORTC scale. The main end-point of the study was the highest observed RTOG/EORTC grade of mucositis.ResultsPatients who smoked during radiotherapy (smokers) were younger than their counterparts who quit smoking (non-smokers), p = 0.06. There were no other differences in the baseline characteristics between smokers and non-smokers. Grade III/IV acute mucositis was observed in 43.5% of all patients. The percentage of patients with grade III/IV acute mucositis was similar in smokers and non-smokers (46% vs. 42%, p = 0.71). Nine patients (smokers [13.5%]; non-smokers [4%], p = 0.05) required prolonged hospitalization to heal mucositis.ConclusionsIn the whole group, smoking during radiotherapy was not related to acute mucosal toxicity evaluated as the rate of the highest observed grade of mucositis.     

Clinical application of recombinant human erythropoietin for treatments in patients with head and neck cancer

Summary The therapeutic effects of intravenous recombinant human erythropoietin (r-hEPO) administration on anemia induced by radiation therapy (3 cases), chemotherapy (18 cases) and combined therapies (5 cases) in patients with head and neck malignancies were examined. The effectiveness was evaluated by the changes in the hemoglobin concentration examined before and after the r-hEPO administration. The r-hEPO administration combined with anticancer therapies improved anemia induced by all three treatments. The therapeutic effectiveness of r-hEPO injection was also noted on anemia induced by all of four different chemotherapeutic regimens that have been ordinarily used for head and neck malignancies. Furthermore, the efficacy of the different dose schedules, 3000 IU (12 cases) or 6000 IU (14 cases), three times a week, was compared. Both of the r-hEPO dose schedules were effective for anemia, but the efficacy of 6000 IU was superior to that of 3000 IU. No significant changes were observed in the number of white blood cells and platelets and the results of biochemical examinations after the r-hEPO injection. There were no objective side-effects related to the r-hEPO administration. These results suggest that anemia induced by chemotherapy and/or radiotherapy could be prevented by r-hEPO administration. The addition of r-hEPO to anticancer therapies would make it possible to pursue the planned therapeutic schedules, prevent the decrease of immunity after allogeneic blood transfusion and bring about an improvement in the prognosis of patients with malignancies.     

Establishment of national diagnostic reference levels (DRLs) for radiotherapy localisation computer tomography of the head and neck

Aim

The aim of this research is to establish if variation exists in the dose delivered for head and neck (HN) localisation computed tomography (CT) imaging in radiation therapy (RT); to propose a national diagnostic reference levels (DRLs) for this procedure and to make a comparison between the national DRL and a DRL of a European sample.

Immunotherapy for head and neck cancer

Head and neck cancer represents a challenging disease. Despite recent treatment advances, which have improved functional outcomes, the long-term survival of head and neck cancer patients has remained unchanged for the past 25 years. One of the goals of adjuvant cancer therapy is to eradicate local regional microscopic and micrometastatic disease with minimal toxicity to surrounding normal cells. In this respect, antigen-specific immunotherapy is an attractive therapeutic approach. With the advances in molecular genetics and fundamental immunology, antigen-specific immunotherapy is being actively explored using DNA, bacterial vector, viral vector, peptide, protein, dendritic cell, and tumor-cell based vaccines. Early phase clinical trials have demonstrated the safety and feasibility of these novel therapies and the emphasis is now shifting towards the development of strategies, which can increase the potency of these vaccines. As the field of immunotherapy matures and as our understanding of the complex interaction between tumor and host develops, we get closer to realizing the potential of immunotherapy as an adjunctive method to control head and neck cancer and improve long-term survival in this patient population.     

Effects of remedies made in patient setup process on residual setup errors and margins in head and neck cancer radiotherapy based on 2D image guidance

AimPatient setup errors were aimed to be reduced in radiotherapy (RT) of head-and-neck (H&N) cancer. Some remedies in patient setup procedure were proposed for this purpose.BackgroundRT of H&N cancer has challenges due to patient rotation and flexible anatomy. Residual position errors occurring in treatment situation and required setup margins were estimated for relevant bony landmarks after the remedies made in setup process and compared with previous results.Materials and methodsThe formation process for thermoplastic masks was improved. Also image matching was harmonized to the vertebrae in the middle of the target and a 5 mm threshold was introduced for immediate correction of systematic errors of the landmarks. After the remedies, residual position errors of bony landmarks were retrospectively determined from 748 orthogonal X-ray images of 40 H&N cancer patients. The landmarks were the vertebrae C1–2, C5–7, the occiput bone and the mandible. The errors include contributions from patient rotation, flexible anatomy and inter-observer variation in image matching. Setup margins (3D) were calculated with the Van Herk formula.ResultsSystematic residual errors of the landmarks were reduced maximally by 49.8% (p ≤ 0.05) and the margins by 3.1 mm after the remedies. With daily image guidance the setup margins of the landmarks were within 4.4 mm, but larger margins of 6.4 mm were required for the mandible.ConclusionsRemarkable decrease in the residual errors of the bony landmarks and setup margins were achieved through the remedies made in the setup process. The importance of quality assurance of the setup process was demonstrated.     

Predicting toxicity for head and neck cancer patients undergoing radiation therapy: an independent and external validation of MDASI-HN based nomogram

AimWe conducted a study to validate the MDASI-HN based nomogram, which is used to predict the acute toxicities in head and neck cancer patients undergoing radiation therapy with or without chemotherapy.BackgroundTolerance to radiation varies from patient to patient and also depends on various other factors like tumor volume, dose of radiation, chemotherapy. Predicting the toxicities allow us to identify potential candidates who are likely to have a higher toxicity and, in addition, evaluates the nomogram when done on an independent group of patients.Materials and MethodsSixty biopsy confirmed head and neck cancer patients undergoing radiation were the subjects of the study. The patients completed patient reported outcome instrument (PRO) MDASI-HN questionnaire at the beginning and at the fifth week of radiation. The baseline score obtained was used to obtain the predicted score using nomogram. The nomogram was also externally validated as per the TRIPOD guidelines.ResultsThe mean baseline, predicted and score at the fifth week were 27.28 ± 11.04, 73.33 ± 15.51 and 82.62 ± 17.67, respectively, for all sub-sites. A positive, significant correlation (p < 0.01) between the predicted score and the score at the fifth week was seen across all sub sites such as Oral cavity (p = 0.05), Oropharynx (p = 0.02), Hypo pharynx (p = 0.02) and Larynx (p = 0.02).ConclusionThe MDASI-HN questionnaire based nomogram is simple, easily doable and takes into consideration the initial symptoms as well the treatment details; thereby, it is able to predict the toxicities accurately.     

Smoking and other health factors in patients with head and neck cancer

BackgroundInformation on smoking and other health factors in head and neck cancer (HNC) patients throughout treatment, follow-up and survivorship is limited. This study explores patterns of multiple health factors during radiotherapy (RT) and naturalistic long-term follow-up in a convenience sample of patients with HNC.MethodsSmoking, alcohol use and depression were measured at baseline, 4 and 12 weeks post RT for a sub-group of 99 patients who participated in a randomised controlled trial and completed long-term follow-up. These factors plus healthy eating, physical activity and fatigue are also reported from the long-term follow-up component. Smoking was measured by self-report and biochemically, whilst all other variables were by self-report. Where variables were assessed at multiple time points logistic mixed effects regression models determined within-person changes over time.ResultsThere were important discrepancies between self-reported (4–7%) and biochemically verified (13–29%) rates of smoking. Rates of smoking and hazardous alcohol intake were significantly increased at follow-up compared to baseline. Depression rates were observed to be higher at end of RT compared to baseline. At long-term follow-up, fatigue was common and co-occurred with suboptimal healthy eating and hazardous alcohol use.ConclusionClinically important levels of smoking and alcohol consumption post RT in this sample suggest possible targets for intervention beyond treatment into long-term follow-up of patients.     

Comparative study of DNA damage and repair in head and neck cancer after radiation treatment

We compared DNA damage and the efficacy of its repair after genotoxic treatment with γ-radiation of lymphocytes and tissue cells isolated from patients with squamous cell carcinoma of head and neck (HNSCC) and healthy donors. Thirty-seven subjects with HNSCC and 35 healthy donors were enrolled in the study. The extent of DNA damage including oxidative lesions and efficiency of the repair were examined by alkaline comet assay. HNSCC cancer cells were more sensitive to genotoxic treatment and displayed impaired DNA repair. In particular, lesions caused by γ-radiation were repaired less effectively in metastasis of HNSCC than in healthy controls. The differences in radiation sensitivity of cancer and control cells suggested that DNA repair might be critical for HNSCC treatment. We conclude that γ-radiation might be considered as an effective therapeutic strategy for head and neck cancers, including patients in advanced stage of the disease with clear evidence of metastasis.     

The number of CD161 positive Th17 cells are decreased in head and neck cancer patients

Background

Despite lots of research efforts, the pathology of head and neck cancer remains elusive. Accumulating evidence suggests that the innate and adaptive immunity plays an important role in HNSCC (Head and Neck Squamous Cell Carcinoma) development. Recently, a new T helper cell subset additional to the classical Th1 and Th2 cells was identified called Th17 cells, due to their secretion of IL-17. However, Th17 cells also produce additional proinflammatory cytokines and many other cytokines are involved in their differentiation and expansion. It was shown that Th17 cells play a prominent role in host defense but are also associated with the development of autoimmune diseases. The role of Th17 cells in cancer pathogenesis remains nebulous.

Methods

Th17 cells of peripheral blood, primary tumors and metastatic lymph nodes were FACS analyzed for their CD161 expression. Supernatants of the permanent HNSCC cell line BHY were used to induce Th17 cells by HNSCC tumor mileu.

Results

Here we show that Th17 cells from patients with HNSCC downregulate the Th17 cell surface receptor CD161 in peripheral blood as well as in primary tumors and especially in metastatic lymph nodes.

Conclusion

We have showed for the first time alterations of Th17 cell phenotype in HNSCC patients.     

Current status of IMRT in head and neck cancer

Background

IMRT provides highly conformal dose distributions creating non uniform spatial intensity using different segments in the beam.

Material & Methods and Results

Different retrospective studies have shown a high capability of IMRT to treat tumours close to the base of skull. Prospective studies have shown a decrease in xerostomia compared with conventional 3D conformal treatment (3DCRT). Modulation of intensity is performed by the movement of the multileaf collimator (MLC) that can deliver the radiation in different ways, such as static field segments, dynamic field segments and rotational delivery (arc therapy and tomotherapy). There are slight differences among the different techniques in terms of homogeneity, dose conformity and treatment delivery time.

Conclusions

The best method to deliver IMRT will depend on multiple factors such as deliverability, practicality, user training and plan quality.     

A comparative study between open-face and closed-face masks for head and neck cancer (HNC) in radiation therapy

AimTo determine the setup reproducibility in the radiation treatment of Head and Neck (HN) patients using open face head and shoulder masks (OHSM) with customized headrest (CHR) versus standard closed head and shoulder masks (CHSM) and to determine the patient’s level of comfort and satisfaction for both masks.MethodsForty patients were prospectively randomized into two groups using simple random sampling. Group 1 was assigned with CHSMs, immobilized with a standard HR (SHR) while Group 2 was assigned with OHSMs, and immobilized with CHR. Cone beam computed tomography (CBCT) was taken the first 3 days, followed by weekly CBCT (prior treatment) with results registered to the planning CT to determine translational and rotational inter-fraction shifts and to verify accuracy. Mean (M) and standard deviation (SD) of the systematic and random setup errors of the 2 arms in the translational and rotational directions were analyzed, using Independent t-test and Mann–Whitney U test. Patient comfort was measured using a Likert questionnaire.ResultsThe vertical, lateral, longitudinal and Z/roll rotational shifts were not significantly different between the two masks. X/yaw and Y/pitch rotational shifts were significantly greater in Group 2 versus Group 1, for both systematic (p = 0.009 and 0.046, respectively) and random settings (p = 0.016 and 0.020) but still within three degrees. Patients reported higher neck and shoulder comfort (p = 0.020) and overall satisfaction (p = 0.026) using the OHSM with the CHR versus the CHSM with the SHR during CT simulation.ConclusionOpen masks provide comparable yet comfortable immobilization to closed masks for HN radiotherapy.     

Squamous cell carcinoma of the head and neck in the elderly

The incidence of head and neck squamous cell carcinoma (HNSCC) peaks between the fifth and seventh decades of life. With prolongation of life expectancy, however, the proportion of elderly HNSCC patients is also increasing, which makes HNSCC in this life period an important issue for healthcare providers. With features characteristic to the older patient groups coupled with the inherent complexity of the disease, HNSCC in the elderly represents a considerable challenge to clinicians. Indeed, to expedite the progress and improve the healthcare system to meet the needs of this unique population of patients, several essential issues related to the clinical profile, diagnostics, optimal treatment and support are of concern and should be addressed in properly conducted clinical trials.In the present review, we analyzed a literature series comparing different age groups with regard to their clinical characteristics, therapy, outcome and quality of life in an attempt to determine their implications on treatment-decision-making for elderly patients with HNSCC.     

Accuracy of dose calculation on iterative CBCT for head and neck radiotherapy

PurposeTo evaluate the feasibility of the use of iterative cone-beam computed tomography (CBCT) for dose calculation in the head and neck region.MethodsThis study includes phantom and clinical studies. All acquired CBCT images were reconstructed with Feldkamp–Davis–Kress algorithm-based CBCT (FDK-CBCT) and iterative CBCT (iCBCT) algorithm. The Hounsfield unit (HU) consistency between the head and body phantoms was determined in both reconstruction techniques. Volumetric modulated arc therapy (VMAT) plans were generated for 16 head and neck patients on a planning CT scan, and the doses were recalculated on FDK-CBCT and iCBCT with Anisotropic Analytical Algorithm (AAA) and Acuros XB (AXB). As a comparison of the accuracy of dose calculations, the absolute dosimetric difference and 1%/1 mm gamma passing rate analysis were analyzed.ResultsThe difference in the mean HU values between the head and body phantoms was larger for FDK-CBCT (max value: 449.1 HU) than iCBCT (260.0 HU). The median dosimetric difference from the planning CT were <1.0% for both FDK-CBCT and iCBCT but smaller differences were found with iCBCT (planning target volume D_50%: 0.38% (0.15–0.59%) for FDK-CBCT, 0.28% (0.13–0.49%) for iCBCT, AAA; 0.14% (0.04–0.19%) for FDK-CBCT, 0.07% (0.02–0.20%) for iCBCT). The mean gamma passing rate was significantly better in iCBCT than FDK-CBCT (AAA: 98.7% for FDK-CBCT, 99.4% for iCBCT; AXB: 96.8% for FDK_CBCT, 97.5% for iCBCT).ConclusionThe iCBCT-based dose calculation in VMAT for head and neck cancer was accurate compared to FDK-CBCT.     

Body mass index and the risk of head and neck cancer in the Chinese population

ObjectiveTo investigate potential associations between body mass index (BMI) and head and neck cancer (HNC) risk in an East Asian population.MethodsWe conducted a hospital-based multicenter case-control study in East Asia including 921 cases and 806 controls. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CI) for HNC risks by using logistic regression, adjusting on potential confounders.ResultsCompared to normal BMI at interview (18.5–<25 kg/m²), being underweight (BMI < 18.5 kg/m²) was associated with a higher HNC risk (OR = 2.71, 95% CI 1.40–5.26). Additionally, obesity (BMI > 30 kg/m²) was associated with a lower HNC risk (OR = 0.30, 95% CI 0.16–0.57). Being underweight at age 20 was also associated with an increased risk of HNC. However, being underweight at 5 years or 2 years before interview was not associated with a higher risk of HNC.ConclusionWe observed an inverse association between BMI and HNC risk, which is consistent with previous studies in other geographic regions. Being underweight at age 20 was also associated with a higher risk of HNC, suggesting that reverse causality was not the main source of the association.     

Mutational analysis of xenobiotic metabolizing genes (CYP1A1 and GSTP1) in sporadic head and neck cancer patients

CYP1A1 is the phase I enzyme that detoxifies the carcinogen or converts it into a more electrophilic form, metabolized by phase II enzymes like GSTP1. These detoxifying genes have been extensively studied in association with head and neck cancer (HNC) in different ethnic groups worldwide. The current study was aimed at screening genetic polymorphisms of genes CYP1A1 and GSTP1 in 388 Pakistani HNC patients and 150 cancer-free healthy controls, using PCR-SSCP. No already known variants of either gene were found, however a novel frameshift mutation due to insertion of T (g.2842_2843insT) was observed in the CYP1A1 gene. A statistically significant number (5.4%) of HNC cases, with the mean age of 51.75 (±15.7) years, presented this frameshift mutation in the conserved domain of CYP1A1. Another novel substitution mutation in was found in the GSTP1 gene, presenting TA instead of AG. The g.2848A > T polymorphism causes a leucine-to-leucine formation, whereas g.2849G > A causes alanine-to-threonine formation at amino acid positions 166 and 167, respectively. These exonic mutations were found in 9.5% of the HNC patients and in none of the controls. In addition, two intronic deletions of C (g.1074delC and g.1466delC) were also found in 11 patients with a mean age of 46.2 (±15.6) years. In conclusion, accumulation of mutations in genes CYP1A1 and GSTP1 appears to be associated with increased risk of developing HNC, suggesting that mutations in these genes may play a role in the etiology of head and neck cancer.     

Effectiveness of PET/CT with 18F-fluorothymidine in the staging of patients with squamous cell head and neck carcinomas before radiotherapy

Aim

The aim of our study was to compare the staging of the disease declared before anticancer treatment was begun with the staging that was found after the planning PET/CT scanning with ¹⁸F-FLT was performed.

Background

PET/CT in radiotherapy planning of head and neck cancers can facilitate the contouring of the primary tumour and the definition of metastatic lymph nodes.

Materials and methods

Between November 2010 and November 2013, 26 patients suffering from head and neck carcinomas underwent planning PET/CT examination with ¹⁸F-FLT. We compared the staging of the disease and the treatment strategy declared before and after ¹⁸F-FLT-PET/CT was performed.

Results

The findings from ¹⁸FLT-PET/CT led in 22 patients to a change of staging: in 19 patients it led to upstaging of the disease and in 3 patients it led to downstaging of the disease. In one patient, a secondary malignancy was found.

Conclusions

We have confirmed in this study that the use of ¹⁸F-FLT-PET/CT scanning in radiotherapy planning of squamous cell head and neck carcinomas has a great potential in the precise evaluation of disease staging and consequently in the precise determination of target volumes.     

Population-based retrospective study to investigate preexisting and new depression diagnosis among head and neck cancer patients

This study aimed to estimate the pre-cancer prevalence and post-cancer incidence of depression in older adult head and neck cancer patients. Using SEER-Medicare files, cancer was identified from SEER data and depression diagnosis was identified using Medicare claims. Of 3533 head and neck cancer patients, 10.6% were diagnosed with depression during the two years prior to cancer diagnosis, and an additional 8.9% developed depression in the year following cancer diagnosis. This study supports the critical need of screening for depression throughout cancer diagnosis and treatment, as well as a preventative approach in depression development in the older head and neck cancer patient population.     

Immune parameters of mice bearing human head and neck cancer

A xenogeneic human head and neck squamous cell carcinoma (HNSCC) model in immunocompetent mice was evaluated for its requirement of cyclosporine for progressive tumor growth. Tumor growth and T cell functions were assessed in mice receiving cyclosporine treatment for various lengths of time. Tumor cells were injected s.c. on day 1 and cyclosporine was injected i.p. daily on days 1, 1–7, 1–14, 1–21, or for the entire 28 days of tumor growth. All mice developed tumors. These tumors were confirmed to be squamous carcinomas of human origin histologically and by positive staining for human MHC class I antigen expression. Tumors were largest in mice that received cyclosporine for days 1–21 or days 1–28. Increased tumor size was associated with increased serum levels of tumor-reactive antibodies, an increased intratumoral frequency of CD4⁺ and CD8⁺ cells, but a diminished production of interleukin-2 (IL-2) by the tumor infiltrate. Also correlating with increasing tumor size was splenomegaly, a decline in the frequency, but not the absolute levels, of splenic CD4⁺ and CD8⁺ cells, and a diminished capacity to proliferate in response to concanavalin A and to be stimulated to secrete IL-2. The HNSCC tumors contributed to the immune decline since T cell functions were more depressed in the tumor bearers than in control mice receiving only cyclosporine treatment. These results demonstrate that human HNSCC tumor xenografts can grow in mice even with limited cyclosporine treatment, and that the survival of these xenografts may, in part, be due to a tumor-induced decline in select T cell functions.This study was supported by the Medical Research Service of the Department of Veterans Affairs, by grants CA-45080 and CA-48080 from the National Institutes of Health