• MeSH
• imunoterapie MeSH
• nádory hlavy a krku * diagnóza   komplikace   radioterapie   MeSH
• protonová terapie MeSH
• Publikační typ
• rozhovory MeSH

• MeSH
• lidé MeSH
• nádory hlavy a krku * radioterapie   MeSH
• osteoradionekróza * etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH

The impact of the temporal sequence by which cranial radiotherapy (CRT) and platin-based chemotherapy (PCth) are administered on sensorineural hearing loss (SNHL) in pediatric and adolescent central nervous system (CNS) and head-and-neck (HN) cancer patients has not yet been studied in detail. We examined the ototoxic effects of sequentially applied CRT and PCth. This study included children and adolescents with CNS and HN tumors who participated in the multicountry PanCareLIFE (PCL) consortium. Audiological outcomes were compared between patients who received CRT prior to PCth and those who received it afterwards. The incidence, degree and posttreatment progression of SNHL, defined as Muenster classification grade ≥MS2b, were evaluated in 141 patients. One hundred and nineteen patients were included in a time-to-onset analysis. Eighty-eight patients received CRT prior to PCth (Group 1) and 53 patients received PCth before CRT (Group 2). Over a median follow-up time of 1.6 years, 72.7% of patients in Group 1 experienced SNHL ≥ MS2b compared to 33.9% in Group 2 (P < .01). A time-to-onset analysis was performed for 74 patients from Group 1 and 45 patients from Group 2. Median time to hearing loss (HL) ≥ MS2b was 1.2 years in Group 1 and 4.4 years in Group 2 (P < .01). Thus, audiological outcomes were better for patients who received CRT after PCth than before. This finding should be further evaluated and considered within clinical practice in order to minimize hearing loss in children and adolescents with CNS and HN tumors.

• MeSH
• centrální nervový systém MeSH
• dítě MeSH
• kraniální ozáření MeSH
• lidé MeSH
• mladiství MeSH
• nádory hlavy a krku * farmakoterapie   radioterapie   MeSH
• nedoslýchavost * chemicky indukované   epidemiologie   MeSH
• percepční nedoslýchavost * chemicky indukované   epidemiologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND PURPOSE: Radiotherapy (RT) is an integral treatment part for patients with head and neck squamous cell carcinoma (HNSCC), but radioresistance remains a major issue. Here, we use MitoTam, a mitochondrially targeted analogue of tamoxifen, which we aim to stimulate ferroptotic cell death with, and sensitize radioresistant cells to RT. MATERIALS AND METHODS: We assessed viability, reactive oxygen species (ROS) production, disruption of mitochondrial membrane potential, and lipid peroxidation in radiosensitive (UT-SCC-40) and radioresistant (UT-SCC-5) HNSCC cells following MitoTam treatment. To assess ferroptosis specificity, we used the ferroptosis inhibitor ferrostatin-1 (fer-1). Also, total antioxidant capacity and sensitivity to tert-butyl hydroperoxide were evaluated to assess ROS-responses. 53BP1 staining was used to assess radiosensitivity after MitoTam treatment. RESULTS: Our data revealed increased ROS, cell death, disruption of mitochondrial membrane potential, and lipid peroxidation following MitoTam treatment in both cell lines. Adverse effects of MitoTam on cell death, membrane potential and lipid peroxidation were prevented by fer-1, indicating induction of ferroptosis. Radioresistant HNSCC cells were less sensitive to the effects of MitoTam due to intrinsic higher antioxidant capacity. MitoTam treatment prior to RT led to superadditive residual DNA damage expressed by 53BP1 foci compared to RT or MitoTam alone. CONCLUSION: MitoTam induced ferroptosis in HNSCC cells, which could be used to overcome the elevated antioxidant capacity of radioresistant cells and sensitize such cells to RT. Treatment with MitoTam followed by RT could therefore present a promising effective therapy of radioresistant cancers. STATEMENT OF SIGNIFICANCE: Radiotherapy is applied in the treatment of a majority of cancer patients. Radioresistance due to elevated antioxidant levels can be overcome by promoting ferroptotic cell death combining ROS-inducing drug MitoTam with radiotherapy.

• MeSH
• dlaždicobuněčné karcinomy hlavy a krku radioterapie   farmakoterapie   patologie   MeSH
• ferroptóza * účinky léků   MeSH
• lidé MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• nádorové buněčné linie MeSH
• nádory hlavy a krku * radioterapie   patologie   farmakoterapie   MeSH
• peroxidace lipidů * účinky léků   MeSH
• reaktivní formy kyslíku * metabolismus   MeSH
• spinocelulární karcinom radioterapie   patologie   farmakoterapie   MeSH
• tamoxifen farmakologie   MeSH
• tolerance záření * účinky léků   MeSH
• viabilita buněk účinky léků   účinky záření   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Risk factors for developing osteoradionecrosis (ORN) are well known, but less is known about factors influencing the interval between radiotherapy and the onset of ORN. Also, it is unknown whether there is any specific period post-radiotherapy with a reduced probability of ORN when irradiated teeth require extraction. PURPOSE: The primary aim of this study was to identify factors influencing the interval in developing ORN in the following subgroups of patients: (1) patients who spontaneously developed ORN, (2) surgical-intervention-related ORN with a particular focus on patients after mandibulectomy. The secondary aim was to attempt to identify a possible time for safer dental intervention after primary treatment. MATERIALS AND METHODS: The authors retrospectively analysed 1608 head and neck cancer (HNC) patients treated in a single centre. Time intervals were measured from the end of radiotherapy to the development of ORN and further analysed in the subgroups listed above. RESULTS: In all, 141 patients (8.8%) developed intra-oral ORN. Median time from radiotherapy to ORN development in the whole cohort was 9 months. Median interval for spontaneous ORN was 8 months, 6.5 months for intervention-related ORN, and 15 months for patients post-mandibulectomy. In patients who required dental extraction preradiotherapy, median interval of ORN onset was 5 months. CONCLUSION: In our study, a slightly higher proportion of patients with intervention developed ORN earlier in comparison with spontaneous ORN. The period from 12-18 months after radiotherapy was identified as having the highest probability of developing ORN in patients after mandibulectomy. A time for safer dental intervention after primary treatment was not identified.

• MeSH
• dospělí MeSH
• extrakce zubů * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mandibulotomie MeSH
• nádory hlavy a krku radioterapie   chirurgie   MeSH
• osteoradionekróza * etiologie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

As the great majority of gene expression (GE) biodosimetry studies have been performed using blood as the preferred source of tissue, searching for simple and less-invasive sampling methods is important when considering biodosimetry approaches. Knowing that whole saliva contains an ultrafiltrate of blood and white blood cells, it is expected that the findings in blood can also be found in saliva. This human in vivo study aims to examine radiation-induced GE changes in saliva for biodosimetry purposes and to predict radiation-induced disease, which is yet poorly characterized. Furthermore, we examined whether transcriptional biomarkers in blood can also be found equivalently in saliva. Saliva and blood samples were collected in parallel from radiotherapy (RT) treated patients who suffered from head and neck cancer (n = 8) undergoing fractioned partial-body irradiations (1.8 Gy/fraction and 50-70 Gy total dose). Samples were taken 12-24 h before first irradiation and ideally 24 and 48 h, as well as 5 weeks after radiotherapy onset. Due to the low quality and quantity of isolated RNA samples from one patient, they had to be excluded from further analysis, leaving a total of 24 saliva and 24 blood samples from 7 patients eligible for analysis. Using qRT-PCR, 18S rRNA and 16S rRNA (the ratio being a surrogate for the relative human RNA/bacterial burden), four housekeeping genes and nine mRNAs previously identified as radiation responsive in blood-based studies were detected. Significant GE associations with absorbed dose were found for five genes and after the 2nd radiotherapy fraction, shown by, e.g., the increase of CDKN1A (2.0 fold, P = 0.017) and FDXR (1.9 fold increased, P = 0.002). After the 25th radiotherapy fraction, however, all four genes (FDXR, DDB2, POU2AF1, WNT3) predicting ARS (acute radiation syndrome) severity, as well as further genes (including CCNG1 [median-fold change (FC) = 0.3, P = 0.013], and GADD45A (median-FC = 0.3, P = 0.031)) appeared significantly downregulated (FC = 0.3, P = 0.01-0.03). A significant association of CCNG1, POU2AF1, HPRT1, and WNT3 (P = 0.006-0.04) with acute or late radiotoxicity could be shown before the onset of these clinical outcomes. In an established set of four genes predicting acute health effects in blood, the response in saliva samples was similar to the expected up- (FDXR, DDB2) or downregulation (POU2AF1, WNT3) in blood for up to 71% of the measurements. Comparing GE responses (PHPT1, CCNG1, CDKN1A, GADD45A, SESN1) in saliva and blood samples, there was a significant linear association between saliva and blood response of CDKN1A (R2 = 0.60, P = 0.0004). However, the GE pattern of other genes differed between saliva and blood. In summary, the current human in vivo study, (I) reveals significant radiation-induced GE associations of five transcriptional biomarkers in salivary samples, (II) suggests genes predicting diverse clinical outcomes such as acute and late radiotoxicity as well as ARS severity, and (III) supports the view that blood-based GE response can be reflected in saliva samples, indicating that saliva is a "mirror of the body" for certain but not all genes and, thus, studies for each gene of interest in blood are required for saliva.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory hlavy a krku radioterapie   MeSH
• radiometrie MeSH
• senioři MeSH
• sliny * účinky záření   metabolismus   MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• fotony terapeutické užití   MeSH
• hodnocení rizik statistika a číselné údaje   MeSH
• kvalita života MeSH
• lidé MeSH
• nádory hlavy a krku * diagnóza   radioterapie   MeSH
• náklady na zdravotní péči statistika a číselné údaje   MeSH
• protonová terapie * metody   statistika a číselné údaje   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• lidé MeSH
• nádory hlavy a krku * diagnostické zobrazování   radioterapie   MeSH
• poruchy polykání * diagnostické zobrazování   etiologie   MeSH
• radiační onkologie * MeSH
• radioterapie s modulovanou intenzitou * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Osteoradionecrosis (ORN) is a serious toxicity of head and neck radiotherapy. It predominantly affects the mandible. Extra-mandibular ORN is rare. The aim of this study was to report the incidence and outcomes of extra-mandibular ORNs from a large institutional database. MATERIALS AND METHODS: In total, 2303 head and neck cancer patients were treated with radical or adjuvant radiotherapy. Of these, extra-mandibular ORN developed in 13 patients (0.5%). RESULTS: Maxillary ORNs (n = 8) were a consequence of the treatment of various primaries (oropharynx = 3, sinonasal = 2, maxilla = 2, parotid = 1). The median interval from the end of radiotherapy to the development of ORN was 7.5 months (range 3-42 months). The median radiotherapy dose in the centre of the ORN was 48.5 Gy (range 22-66.5 Gy). Four patients (50%) healed in 7, 14, 20 and 41 months. All temporal bone ORNs (n = 5) developed after treatment to the parotid gland (of a total of 115 patients who received radiotherapy for parotid gland malignancy). The median interval from the end of radiotherapy to the development of ORN was 41 months (range 20-68 months). The median total dose in the centre of the ORN was 63.5 Gy (range 60.2-65.3 Gy). ORN healed in only one patient after 32 months of treatment with repeated debridement and topical betamethasone cream. CONCLUSION: Extra-mandibular ORN is a rare late toxicity and this current study provides useful information on its incidence and outcome. The risk of temporal bone ORN should be considered in the treatment of parotid malignancies and patients should be counselled. More research is required to determine the optimal management of extra-mandibular ORN, particularly on the role of the PENTOCLO regimen.

• MeSH
• celková dávka radioterapie MeSH
• lidé MeSH
• mandibula MeSH
• nádory hlavy a krku * radioterapie   MeSH
• nemoci mandibuly * komplikace   epidemiologie   MeSH
• osteoradionekróza * epidemiologie   etiologie   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND/AIM: This study aimed to identify the progression of carotid artery stenosis (CAS) in patients with head and neck cancer following radiation therapy (RT) by characterizing associated risk factors. PATIENTS AND METHODS: Panoramic radiographs (OPG), computed tomography (CT) scans, cone-beam CT (CBCT) scans, and ultrasonography (US) of 69 patients with head and neck tumors were selected and analyzed to identify the presence of CAS. Data on tumor location, smoking status, hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), and treatment were collected from the patients' medical records. Patients who received chemotherapy or no treatment were excluded from the study. The differential diagnosis of other radiopacities and anatomical landmarks were excluded. Patients were divided into two groups: those with CAS (group1) and those without CAS (group 2) and their clinical information was compared. RESULTS: The overall prevalence of CAS on the panoramic radiographs was 16%. Of the 69 patients, 44 underwent radiography before and after radiotherapy, only seven had mild CAS on radiographs after radiotherapy, and no significant difference in CAS was identified before and after radiotherapy. There were also no differences between the groups regarding age, sex, smoking, hypertension, diabetes mellitus, hyperlipidemia, tumor location, and RT dose before and after radiation (p>0.05). CONCLUSION: Radiotherapy does not seem to affect the prevalence of CAS, although it has been identified in some patients after radiotherapy completion.

• MeSH
• diabetes mellitus * MeSH
• hyperlipidemie * komplikace   MeSH
• hypertenze * komplikace   epidemiologie   MeSH
• lidé MeSH
• nádory hlavy a krku * diagnostické zobrazování   radioterapie   komplikace   MeSH
• počítačová rentgenová tomografie škodlivé účinky   MeSH
• radioterapie škodlivé účinky   MeSH
• rentgendiagnostika panoramatická škodlivé účinky   MeSH
• rizikové faktory MeSH
• stenóza arteria carotis * diagnostické zobrazování   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH