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Introduction: Thanks to modern IGRT procedures, it is possible to track changes in the patient's anatomy and thus calculate the dose distribution for the current anatomical conditions of the patient. This allows the scheduled dose to be compared with the delivered dose. In the case of large discrepancies, it is possible to improve the treatment plan. Radiotherapy, during which the treatment plan is modified, resulting from changes in anatomy, is referred to as adaptive radiotherapy. Material and methods: This study was performed for 30 patients with H&N cancer at the University Hospital in Zielona Góra. All patients were treated with VMAT. The Simultaneous Integrated Technique was used. In each treatment session, set-up verification was performed. Alternating every other day, the CBCT and two orthogonal portal images were made, and position correction prior to each session was performed. For all patients, new planning CT was made after the 11th and 22nd treatment sessions. Dose distributions with the initial plan on CT11 and CT22 were calculated. The initial dose-volume histograms DVH0 were compared with dose-volume histograms DVH11 and DVH22 calculated on CT11 and CT22. Results: We compared the dose distribution in the CTVs and in the most important organs at risk obtained for initial anatomy and dose distributions calculated with the initial plan on the CTs performed after the second and the fourth week of irradiation. The differences between mean doses and V95% to GTV obtained for the initial CT and two other CTs were small. For a few CTs, the values of V95% were smaller by more than 5% points. In most patients, the mean dose in salivary glands increased during treatment. Conclusions: Anatomical changes occurring during radiotherapy in patients with head and neck cancers have little influence on the dose deposited in the Clinical Target Volume. Adaptive therapy may be of particular importance if relapse occurs and re-irradiation.
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Introduction: Radiotherapy (RT) for patients with head and neck squamous cell carcinoma (HNSCC) affects vital functions related to the irradiation volume of the head and neck region and, in addition, has a negative impact on social functioning, thereby significantly impairing patients’ quality of life (QoL). Aim: The aim of this study was to assess changes in the quality of life in patients with head and neck cancer treated with curative RT at 12 months after completion of RT. The aim of this study was to assess the differences between the baseline QoL of patients with early clinical stage HNSCC and at 12 months after curative/radical RT. Material and methods: The prospective clinical study included 92 patients in good general condition (ECOG 0–1 – Eastern Cooperative Oncology Group performance status), without regional or distant metastases, diagnosed with pathomorphologically confirmed early-stage head and neck squamous cell carcinoma treated with definitive RT. All patients participating in the study signed an informed consent form. QoL was assessed using the standard EORTC QLQ-C30 and QLQH&N35 questionnaires. In addition, information on clinical aspects and data relating to socio-demographic factors were obtained from each patient. Statistical analysis was performed using a statistical package (SPSS 17.0). T-test was used for dependent and independent samples. A general linear model was used for repeated measures. Results: Patients’ QoL deteriorated significantly after definitive RT. Worse QoL Core-30 scores in patients 12 months after the end of RT, compared with baseline QoL, before the start of RT, were observed in domains such as physical performance, fulfillment of life roles, cognitive functioning, loss of appetite, fatigue and constipation. For the QLQ-H&N35 questionnaires, patients 12 months after the end of RT reported problems in relation to aspects of life such as senses, mouth opening, dry mouth, thick saliva, pain, and weight loss. Conclusion: RT, even in early clinical stage head and neck cancer, has a negative impact on QoL, despite modern treatment techniques.
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Advanced head and neck squamous cell cancers (HNSCC) have unfavorable prognosis and new therapeutic options are necessary to improve treatment outcomes. The Wnt pathway plays an important role in the pathogenesis and progression of HNSCC. The aim of this study was to assess the effects of a histone deacetylase inhibitor – panobinostat on Wnt-dependent gene expression and on cell migration. Cell viability in HNSCC cell lines (BICR6, CAL27, FaDu, H314, SCC-25) was evaluated by MTT assay. The expression of β-catenin-target genes was assessed by qPCR and TCF/LEF-dependent reporter assay. Protein content was evaluated by Western blot. Cell migration was analyzed by the wound healing assay. Panobinostat showed differential modulation of gene expression. It reduced the level of Axin2 in CAL27 and SCC-25 cells but upregulated its expression in BICR6 and H314 cell lines. Moreover, it diminished the expression of MMP7 in BICR6, H314 and CAL27 cell lines. In contrast, the inhibitor of β-catenin transcriptional activity – PKF118-310 down-regulated the expression of β-catenin-target genes in HNSCC cell lines. Interestingly, panobinostat had opposite effects on cell migration in CAL27 and FaDu where it inhibited or stimulated migration, respectively. On the other hand, PKF118-310 reduced cell migration. The anti-cancer effects of panobinostat in HNSCC cells are rather not related to the inhibition of Wnt signaling. PKF118-310 attenuates Wnt signaling, but only in a limited number of HNSCC cell lines. Importantly, the inhibition of Wnt pathway reduces the capacity of cells for migration suggesting that it may potentially therapeutically reduce cell invasion.
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Introduction: Microvascular free tissue transfer enables the reconstruction of complex head and neck defects. The aim of the study was to assess the results of treatment of patients undergoing reconstructive surgery and to identify factors affecting these results, with particular reference to patient’s age. Materials and Methods: All patients who underwent free-flap head and neck reconstruction in our institution between 2010 and 2017 were included in this retrospective study. A series of 66 patients met the inclusion criteria and were divided into 2 age groups: group G1 aged <65 years (n = 41) and group G2 aged ≥65 years (n = 25). Minor local complications and general complications as well as comorbidities were analyzed. Results: No correlation was found between advanced age and the risk of free flap failure as well as the incidence of local minor complications. General complications were more frequent in the G2 group (32%) than in the G1 group (19.5%), although this is not a statistically significant difference. A statistically significant difference was found between the age and the patient’s health status according to ASA (P = 0.010). In the younger low-risk group, 12 patients (29.3%) had general and local complications, while in the older low-risk group only 1 (4%). General and local complications were found in 5 (12.2%) high-risk G1 patients and in 7 (28%) high-risk G2 patients. Conclusion(s): Patients with advanced head and neck malignant tumors should undergo reconstructive microsurgery regardless of age.
EN
Introduction: Microvascular free tissue transfer enables the reconstruction of complex head and neck defects. The aim of the study was to assess the results of treatment of patients undergoing reconstructive surgery and to identify factors affecting these results, with particular reference to patient’s age. Materials and Methods: All patients who underwent free-flap head and neck reconstruction in our institution between 2010 and 2017 were included in this retrospective study. A series of 66 patients met the inclusion criteria and were divided into 2 age groups: group G1 aged <65 years (n = 41) and group G2 aged ≥65 years (n = 25). Minor local complications and general complications as well as comorbidities were analyzed. Results: No correlation was found between advanced age and the risk of free flap failure as well as the incidence of local minor complications. General complications were more frequent in the G2 group (32%) than in the G1 group (19.5%), although this is not a statistically significant difference. A statistically significant difference was found between the age and the patient’s health status according to ASA (P = 0.010). In the younger low-risk group, 12 patients (29.3%) had general and local complications, while in the older low-risk group only 1 (4%). General and local complications were found in 5 (12.2%) high-risk G1 patients and in 7 (28%) high-risk G2 patients. Conclusion(s): Patients with advanced head and neck malignant tumors should undergo reconstructive microsurgery regardless of age.
EN
Exosomes are membrane vesicles of endocytic origin that participate in inter-cellular communication. Environmental and physiological conditions affect composition of secreted exosomes, their abundance and potential influence on recipient cells. Here, we analyzed protein component of exosomes released in vitro from cells exposed to ionizing radiation (2Gy dose) and compared their content with composition of exosomes released from control not irradiated cells. Exosomes secreted from FaDu cells originating from human squamous head and neck cell carcinoma were analyzed using LC-MS/MS approach. We have found that exposure to ionizing radiation resulted in gross changes in exosomal cargo. There were 217 proteins identified in exosomes from control cells and 384 proteins identified in exosomes from irradiated cells, including 148 "common" proteins, 236 proteins detected specifically after irradiation and 69 proteins not detected after irradiation. Among proteins specifically overrepresented in exosomes from irradiated cells were those involved in transcription, translation, protein turnover, cell division and cell signaling. This indicated that exosomal cargo reflected radiation-induced changes in cellular processes like transient suppression of transcription and translation or stress-induced signaling.
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Head and neck squamous cell carcinoma (HNSCC) is one of the leading cancers by incidence worldwide. The risk of these cancers is strictly associated with alkylation factors present in tobacco smoke. The crucial role in preventing DNA alkylation is played by O6-methylguanine-DNA methyltransferase (MGMT). Dysfunction or lack of MGMT is associated with an increased risk of cancer. The aim of the study was to assess the influence of MGMT polymorphisms: rs12917 and rs11016879 on HNSCC risk and course. The study consisted of 69 HNSCC patients and 242 healthy individuals. Case samples were taken from resected tumour tissue. The control group comprised samples of epithelial cells collected from mucous membranes using swabs. DNA samples were genotyped by employing the 5' nuclease assay for allelic discrimination using TaqMan SNP Genotyping Assays. The significance between distributions of genotypes and alleles was tested using Pearson's χ2 test analysis. Our results indicated that the MGMT rs12917 TT genotype increases the risk of HNSCC. The MGMT rs11016879 AG genotype and A allele were associated with increased HNSCC risk. We noted higher risk of nodal metastasis in rs11016879 AA homozygotes. Mechanisms leading to MGMT enzymatic defect are unknown and hence further studies need to be carried out. Our data suggest that the examined polymorphisms may be considered as potential prognostic factors for HNSCC risk and outcome. Further studies are necessary to verify our results.
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Purpose: The purpose of the study was to examine the effect of using videos during enteral feeding training on the level of relevant knowledge and practice. Materials and methods: A randomized controlled quasi-experimental, post-test research design was used. We included 33 patients and relatives in the video group while 31 patients their relatives in the control group. In video group, the video recording was shown to the relatives in addition to verbal training however only verbal training was given in the control group. The relatives’ level of knowledge and practice score was evaluated. Results: Mean enteral feeding knowledge scores of patient relatives were found to be 76.7 ± 7.97 in the video group and 42.1 ± 12.57 in the control group. Mean enteral feeding practice scores were as follows: 19.64 ± 3.3 for the video group and 13 ± 3.63 for the control group. Conclusions: It was concluded that the enteral feeding training provided by using the video method increased the knowledge and practice levels of patient relatives. Implications for Practice: Video material prepared for the clinic will be a guide for clinical nurses and help them in their enteral feeding training and care planning.
EN
Background: Head and neck neoplasms stand for 6% of all malignant neoplasms worldwide. Chemotherapy has limited use due to the biological properties of the tumor (in the majority of cases moderately and poorly differentiated squamous cell carcinoma). The fundamental molecule used in treatment is cisplatin and its derivates, that can be associated with fluorouracil. The new chemotherapeutic agents are not in common use during the treatment of head and neck malignancies. However, the use of low molecular weight complexes Pd (II) carries the potential of being more effective in therapy. Material and Methods: Fifty-one patients, 30 men and 21 women (aged 52.9 ± 12.1 years) with head and neck cancer were included in the study. Fifty-one healthy subjects, 31 men and 20 women, (aged 54.1 ± 14.7 years) years formed the control group. Antioxidant enzymes, superoxide dismutase, and catalase activities in erythrocytes were examined. Results: An increased level of antioxidant enzymes was seen in the blood samples from patients with head and neck cancer after incubation with Pd (II) complex. In the group we obtained a statistically significant result p = <0.001. Discussion: That project may contribute to the development of new, more efficient head and neck cancer treatment strategies. In our opinion, the results can be used in the future to develop a valuable prognostic marker of the disease. This is important because the initial phase of cancer is asymptomatic. The search for factors involved in pathogenesis translates into economic benefits and makes therapy more effectiveness through the reduction of treatment expenses.
EN
Introduction: Assessment of usefulness of instrumental method of evaluation of dysphagia in creating a therapeutic plan among patients after oropharyngeal cancer surgery with free flap reconstruction. Material and Method: Seven patients after oropharyngeal cancer surgery with free flap reconstruction hospitalized from January to September 2016 in the ENT Department of Warsaw Medical University were included in this study. All patients underwent few times after surgery: clinical swallowing examination, water swallowing screening test and fiberoptic endoscopic evaluation of swallowing and/or videofluoroscopy. Results: All patients were diagnosed with dysphagia and had unitentional weight loss (average 5,9% of initial weight during 3 months). In water swallowing test only three participant achieved negative score for 5 ml, and two for 10 ml, 20 ml and 90 ml of water. Fiberoptic endoscopic evaluation of swallowing was analyzed for swallowing patterns and laryngeal pathology. FEES showed following abnormalities: aspiration (saliva, liquid), penetration (puree, liquid), premature swallowing (liquid, puree) and multiswallowing (liquid, puree, solid food), retention (saliva, puree, liquid, solid food). Videofluroscopy showed on the first place problems with oral phase of swallowing: difficulty forming and propeling bolus, tongue pumping movements, oral cavity residue, premature spillage and delayed oral onset. During the pharyngeal phase we observed: residue in valleculae and piriform sinuses, reduced laryngeal elevation, penetration and aspiration, multiple swallows. Conclusion: Instrumental assessment of swallowing helps during diagnostic and therapeutic process of patients with dysphagia after oncological treatment. a.
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Radiotherapy causes molecular changes observed at the level of body fluids, which are potential biomarker candidates for assessment of radiation exposure. Here we analyzed radiotherapy-induced changes in a profile of small metabolites detected in sera of head and neck cancer patients using the gas chromatography coupled with mass spectrometry approach. There were about 20 compounds, including carboxylic acids, sugars, amines and amino acids, whose levels significantly differed between pre-treatment and post-treatment samples. Among metabolites upregulated by radiotherapy there was 3-hydroxybutyric acid, whose level increased about three times in post-treatment samples. Moreover, compounds affected by irradiation were associated with several metabolic pathways, including protein biosynthesis and amino acid metabolism.
EN
Introduction: The aim of this study was the evaluation of volume and dose differences in selected structures in patients with head and neck cancer during treatment on Helical TomoTherapy (HT) using a commercially available deformable image registration (DIR) tool. We attempted to identify anatomical and clinical predictive factors for significant volume changes probability. Material and methods: According to our institutional protocol, we retrospectively evaluated the group of 20 H&N cancer patients treated with HT who received Adaptive Radiotherapy (ART) due to soft tissue alterations spotted on daily MVCT. We compared volumes on initial computed tomography (iCT) and replanning computed tomography (rCT) for clinical target volumes (CTV) – CTV1 (the primary tumor) and CTV2 (metastatic lymph nodes), parotid glands (PG) and body contour (B-body). To estimate the planned and delivered dose discrepancy, the dose from the original plan was registered and deformed to create a simulation of dose distribution on rCT (DIR-rCT). Results: The decision to replan was made at the 4th week of RT (N = 6; 30%). The average volume reduction in parotid right PG[R] and left PG[L] was 4.37 cc (18.9%) (p < 0.001) and 3.77 cc (16.8%) (p = 0.004), respectively. In N = 13/20 cases, the delivered dose was greater than the planned dose for PG[R] of mean 3 Gy (p < 0.001), and in N = 6/20 patients for PG[L] the mean of 3.6 Gy (p = 0.031). Multivariate regression analysis showed a very strong predictor explaining 88% (R2 = 0.88) and 83% (R2 = 0.83) of the variance based on the mean dose of iPG[R] and iPG[L] (p < 0.001), respectively. No statistically significant correlation between volume changes and risk factors was found. Conclusions: Dosimetric changes to the target demonstrated the validity of replanning. A DIR tool can be successfully used for dose deformation and ART qualification, significantly reducing the workload of radiotherapy centers. In addition, the mean dose for PG was a significant predictor that may indicate the need for a replan.
EN
Background: Head and neck neoplasms stand for 6% of all malignant neoplasms worldwide. Chemotherapy has limited use due to the biological properties of the tumor (in the majority of cases moderately and poorly differentiated squamous cell carcinoma). The fundamental molecule used in treatment is cisplatin and its derivates, that can be associated with fluorouracil. The new chemotherapeutic agents are not in common use during the treatment of head and neck malignancies. However, the use of low molecular weight complexes Pd (II) carries the potential of being more effective in therapy. Material and Methods: Fifty-one patients, 30 men and 21 women (aged 52.9 ± 12.1 years) with head and neck cancer were included in the study. Fifty-one healthy subjects, 31 men and 20 women, (aged 54.1 ± 14.7 years) years formed the control group. Antioxidant enzymes, superoxide dismutase, and catalase activities in erythrocytes were examined. Results: An increased level of antioxidant enzymes was seen in the blood samples from patients with head and neck cancer after incubation with Pd (II) complex. In the group we obtained a statistically significant result p = <0.001. Discussion: That project may contribute to the development of new, more efficient head and neck cancer treatment strategies. In our opinion, the results can be used in the future to develop a valuable prognostic marker of the disease. This is important because the initial phase of cancer is asymptomatic. The search for factors involved in pathogenesis translates into economic benefits and makes therapy more effectiveness through the reduction of treatment expenses.
EN
Patients with head and neck cancers have an increased risk of second malignant neoplasm occurrence (25% in long-term follow-up, 4% yearly). Most patients with a primary tumor can be treated with organ-preserving strategies including radiotherapy (RT) or chemoradiotherapy (CRT). Very often after radical surgical excision there are indications for adjuvant radiotherapy. However, if recurrence or second malignancy will develop after definitive primary RT, there are limitation to use therapeutic dose of radiation again for the same area. Salvage surgery is regarded as the only curative option in those cases. In our study we analysed 3 patients, who presented with head and neck second cancer in the area of hypopharynx, within 10-25 years after primary radiotherapy due to oropharyngeal and laryngeal cancer. A total pharyngectomy with larynx preservation and bilateral neck dissection were performed in the first case and the radial forearm free flap (RFFF) was used for reconstruction of the pharynx. Second patient, due to perilaryngeal invasion in radiological images, underwent total pharyngolaryngectomy with selective bilateral cervical lymph nodes dissection and digestive track was restored also with RFFF. The third patient had previously undergone laryngectomy and after total pharyngectomy the free autologous jejunal flap (FAJF) was used for reconstruction. The main goal of reconstruction after salvage surgery due to hypopharyngeal cancer is to reconstruct the digestive tract. The other important aspect is to optimize the anatomy for voice rehabilitation and swallowing. Unfortunately, radiation and chemotherapy impair wound healing, which indicates increased risk of postoperative complications and makes salvage surgery results unpredictable.
EN
Objectives Head and neck cancer (HNC) is one of the most common cancers. Most exogenous HNC is head and neck squamous cell carcinomas. Scientists are striving to develop diagnostic tests that will allow the prognosis of HNC. The aim of the study was to determine the risk of HNC. The research concerned changes caused by polymorphisms in genes encoding proteins responsible for the metabolism of xenobiotics. Material and Methods In group of 280 patients with HNC, the occurrence of polymorphic variants in NAT1(rs72554606), NAT2(rs1799930), CYP1A(rs1799814), CYP2D(rs3892097) were studied with TaqMan technique. The control group consisted of 260 cancer free people. The TNM scale was analyzed. Gene interactions of genotyped polymorphisms were investigated. The effects of smoking and alcohol consumption on HNC were assessed. Results The results indicated an increased risk of HNC in NAT1 polymorphisms in the GC genotype (OR = 1.772, 95% CI: 1.184–2.651, p = 0.005) and NAT2 polymorphism in the GA genotype (OR = 1.506, 95% CI: 1.023–2.216, p = 0.037). The protective phenomenon in the CYP1A polymorphism the GT genotype (OR = 0.587, 95% CI: 0.381–0.903, p = 0.015) and the TT genotype (OR = 0.268, 95% CI: 0.159–0.452, p = 0.001). The coexistence of GA-GC polymorphisms (OR = 2.687, 95% CI: 1.387–5.205, p = 0.003) in NAT2-NAT1 genes increases the risk of HNC. Risk-reducing effect in the polymorphism GG-GT (OR = 0.340, 95% CI: 0.149–0.800, p = 0.011), GG-TT (OR = 0.077, 95% CI: 0.028–0.215, p < 0.0001), GA-TT (OR = 0.250, 95% CI: 0.100–0.622, p = 0.002), AA-GT (OR = 0.276, 95% CI: 0.112–0.676, p = 0.002) in NAT2-CYP1A genes. In the CYP2D-CYP1A genes in the polymorphisms CT-CC (OR = 0.338, 95% CI: 0.132–0.870, p = 0.020), TT-GG (OR = 0.100, 95% CI: 0.027–0.359, p = 0.001), TT-GC (OR = 0.190, 95% CI: 0.072–0.502, p = 0.0004), TT-CC (OR = 0.305, 95% CI: 0.107–0.868, p = 0.024). Correlation was noted between cigarette smoking and HNC (OR = 7.297, 95% CI: 4.989–10.674, p < 0.0001) and consuming alcohol (OR = 1.572, 95% CI: 1.003–2.464, p = 0.047). Conclusions The CYP1A polymorphism shows a protective association with HNC. On the other hand, NAT2, NAT1 polymorphism influence the susceptibility to developing HNC. The coexistence of the NAT2-NAT1 genotypes increases the risk of HNC. In contrast, NAT1-CYP1A and CYP1A-CYP2D reduce this risk. Smoking and alcohol consumption increase the incidence of HNC.
EN
A review on the radiobiological modeling of radiation-induced hypothyroidism after radiation therapy of head-and-neck cancers, breast cancer, and Hodgkin’s lymphoma is presented. The current review is based on data relating to dose-volume constrains and normal tissue complication probability (NTCP) as a function of either radiobiological or (pre)treatment-clinical parameters. Also, these data were explored in order to provide more helpful criteria for radiobiological optimization of treatment plans involving thyroid gland as a critical normal organ.
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