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The availability and non-invasiveness of circulating cell-free DNA (cfDNA) opens up new possibilities for real-time serial testing. The relationship between cfDNA concentration, clinical factors and suitability for monitoring was analyzed in patients with newly diagnosed anal squamous cell carcinoma (ASCC).Blood samples were collected at several points during and after treatment. Patients were homogeneously treated with chemoradiotherapy.The concentration of cfDNA strongly correlated with the tumor volume (Substantial changes in plasma cfDNA content can be observed after chemoradiotherapy for ASCC. However, the small number of cases studied makes it difficult to assess the usefulness of the cfDNA test.

Severe xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer. Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction of radiation-related toxicity. The aim of this study was to create an efficient prognostic miRNA-based test for severe, patient-rated xerostomia 3 months after primary treatment.This prospective study enrolled patients with oropharyngeal cancer treated between 2016 and 2018 in 3 centers in Poland. The primary endpoint was severe (grade ≥3) xerostomia as assessed by the European Organisation for Research and Treatment of Cancer HN-35 questionnaires. Initially, a group of 10 patients with severe xerostomia was randomly selected and matched with a comparative group of 10 patients without severe xerostomia. Samples were collected before radiation therapy, after receiving 20 Gy, and within 24 hours after treatment completion. Quantitative real-time polymerase chain reaction arrays (QIAGEN, Hilden, Germany) were used to quantify expression levels of 752 miRNAs in the serum at all timepoints. The resulting logistic-regression based model was validated in additional 60 patients: 30 with grade3 xerostomia and 30 without.Of 152 eligible patients, we successfully recruited 111 patients. Severe xerostomia 3 months after treatment was reported by 63 patients (56.8%). Mean dose delivered to parotid glands was higher in both the exploratory and validation cohort. The model based on miR-185-5p and miR-425-5p expression levels measured before the start of radiation therapy had an area under the curve of 0.96 (95% confidence interval, 0.88-1.00). The model based on the same miRNAs remained robust when parameters were measured after 20 Gy (area under the curve 0.90; 95% confidence interval, 0.75-1.00). These results were confirmed in the validation group. In the validation group, preradiation therapy model application yielded 73.3% sensitivity and 80.0% specificity. In the samples taken after 20 Gy, the same 2 miRNAs yielded 67.7% sensitivity and 72.4% specificity. The model including pretreatment miR-185-5p and miR-425-5p levels together with mean parotid dose yielded 90.0% sensitivity and 80.0% specificity. In the validation cohort, this model yielded 80.6% sensitivity and 55.2% specificity. The model based on miRNA levels measured after 20 Gy and mean parotid dose had 80.0% sensitivity and 100% specificity in the exploratory group. In the validation cohort its performance fell to 71.0% sensitivity and 58.6% specificity.Serum expression levels of miR-425-5p and miR-185-5p measured before the start of radiation therapy or during therapy (after 20 Gy) had significant prognostic value for the occurrence of severe xerostomia 3 months after treatment completion. The variability explained by miRNAs appears to be, at least partially, independent from that related to the dosimetric data.

Between January 2017 and July 2018 103 patients were included in a prospective study of erythropoietin (EPO) monitoring. The group consisted of 33% patients with oropharynx, 29% with oral cavity, 13% with nasopharynx, 6% with larynx, 6% with hypopharynx, 8% with unknown primary cancer, 4% with nasal cavity, and 1% with salivary gland cancer. Clinic stage: T4 - 50, T3 - 21, T2 - 14, T1 - 10, T0 - 8, and N3 - 19, N2 - 61, N1 - 10, N0 - 13. All patients received from one to four cycles of induction chemotherapy. EPO was measured in blood serum by enzyme-labelled chemiluminescent immunometric assay, using an Immulite 2000XPi analyser before the administration and on day 11 of each chemotherapy cycle. During induction chemotherapy the EPO level was elevated in all patients, which is expressed by means of medians: 10.7 (p = 0.000001) in the middle of cycle 1; 10.9 (p = 0.66) before cycle 2; 14.35 (p = 0.000177) in the middle of cycle 2; 14.95 (p = 0.39) before cycle 3, 17.00 (p = 0.00078) in the middle of cycle 3, and 20.9 after cycle 3 (p = 0.41). The correlation analysis conducted indicates that the administration of one chemotherapy dose results in higher EPO release (two-fold increase in EPO concentration) which intensifies reticulocytes (REC) production but without haemoglobin concentration in reticulocytes (HGB-REC) growth. In consequence, it leads to a decrease in RBC and HGB concentration (29-32 cases). The administration of two and three chemotherapy doses results in the subsequent higher release of EPO, which does not intensify REC production. In consequence, anaemia increases (35 cases).

The retrospective chart review of 110 patients with T2 supraglottic cancer who underwent radiotherapy was performed to correlate tumor volume with other prognostic factors and to analyze its impact on treatment results. Patients with involved nodes, poor histopathological tumor differentiation, or hemoglobin concentration ≤ 14.3 g/dl had significantly larger tumors. Patients with large tumors had significantly lower 5-year local control rate, overall survival rate and presented significantly higher risk of nodal involvement and the ratio of poor histopathological differentiation of the tumor. Tumor volume significantly impacts radiotherapy outcome and should be considered to optimize treatment strategy for patients with T2 supraglottic cancer.

Extraskeletal Ewing's sarcoma arising in the head and neck region is an extremely rare malignant neoplasm. We describe the unusual case of a tumor originating in the larynx of a 68-year-old male with hoarseness and occasional aphonia. We report successful treatment with sequential chemo- and radiotherapy. Complete regression and larynx preservation with voice function recovery was achieved. To our knowledge, this is the first report of this type of tumor in the larynx with cartilage invasion that documents the effectiveness of radiotherapy as an alternative to surgical management. At present, after 30 months of follow-up, the patient is free of tumor relapse and in very good condition.

Wegener's granulomatosis is a rare disease (10 per 1 000 000 new cases per year), etiologically connected with necrotizing vasculitis of small to medium-size vessels. The disease occurs predominantly in the upper respiratory tract, lungs and kidneys, but any organ may be affected during the course of the illness. It may be difficult to diagnose, especially when c-ACNA antibodies (serologic symptom of Wegener's granulomatosis) are undetectable and chest X-ray is normal. Early diagnosis is crucial for treatment results. Untreated disease may lead to death. Cyclophosphamide used simultaneously with prednisone is the treatment of choice as the first line procedure. Resistance to standard systemic treatment may be a significant problem. New drugs (rituximab, infliximab) are still under clinical investigation, with promising results. Very limited data concerning effectiveness of radiation therapy exist. We present a report of a female patient with solitary form of Wegener's granulomatosis located in the facial region, who underwent successful radiation therapy with a complete response.

To evaluate the feasibility and preliminary results of intraoperative radiotherapy (IORT) with low-energy photons as a boost in patients with early-stage oral cancer with the indications for postoperative radiotherapy. Between 2003 and 2006, 16 patients with early-stage cancer of mobile tongue (n = 10 [63%]) or floor of the mouth (n = 6 [37%]) treated at Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland, were evaluated for IORT boost with the INTRABEAM®System (Carl Zeiss Surgical GmbH; IORT-PRS) because of the high risk of local recurrence due to positive margins on frozen pathologic section. After tumor resection, the applicator was positioned in the tumor bed. The applicator’s diameter (range: 1.5–5 cm) was selected to encompass high-risk area of tumor recurrence. The dose (5 Gy, 7 Gy, or 7.5 Gy) was applied according to tumor volume and bone proximity. External-beam radiotherapy (EBRT) was provided to the tumor bed in all patients (50 Gy) and to the nodal area, when needed. Toxicity and local tumor control were assessed. Median follow-up was 36 months. IORT did not increase acute mucosal reaction. Local tumor control was found in all cases. Early mucosal reaction did not exceed 3 according to the RTOG scale and healed in median time of 35 days after completion of EBRT. No late adverse effects were observed. This preliminary report has demonstrated the feasibility of IORT-PRS for patients with early oral cancer with the indications for postoperative radiotherapy. This method may be considered an alternative boost technique, although additional studies are needed to establish long-term results in a larger group of patients.

Summary Background Irradiation of salivary glands during the treatment of head and neck cancer may lead to an alteration in the amount of saliva produced. Because of this, patients can suffer dryness of the mouth with oral discomfort, taste disturbance and dental decay. Aim The aim of this study is to estimate late toxicity dependence on radiotherapy method. The main goal is to investigate the correlations between the radiation doses in salivary glands and their salivary excretion fractions (SEF) measured by dynamic scintigraphy. Materials/Methods In 40 patients with pharyngeal and laryngeal cancer irradiated by IMRT or conformal 3D to a total dose of 62.5–72.0Gy, parotid SEFs were measured. Parotid dose-volume histograms were obtained from 3D computer treatment planning. SEF measurements were performed before (baseline), and 6 weeks and 6 months after radiotherapy by 185MBq 99 Tc injected intravenously and next SEF rates were analysed in relation to radiation doses accumulated. The late radiation toxicity of salivary glands was tested according to the CTC v. 3.0 and SOMA-LENT scales. The non-parametric Mann Whitney test was used for the estimation of relationships. Results Pre- and post-treatment SEFs were measured in 31 patients treated by IMRT and in 9 patients treated by 3D CRT. Six weeks after radiotherapy SEF was generally lower by 34%, and 6 months after irradiation by 29.3% in IMRT technique. In 3D CRT relatively it was lower: after 6 weeks by average 52% and after 6 months by 35.5%. Late radiation toxicity of salivary glands was observed at a similar level according to CTC and SOMA-LENT scales in both methods of radiotherapy. Conclusions The level of SEF in parotid glands measured 6 weeks after radiotherapy clearly reflects the dose-response relationship of irradiated salivary tissue; 6 months later changes of SEF are the result of partial recovery of parotids. The results of sparing salivary glands can be optimized in the future; that is, a further reduction of xerostomia can be achieved by using improved IMRT techniques and focusing on sparing major and minor salivary glands.

Brain metabolism after surgery and postoperative radiotherapy (pRT) because of primary brain tumors was assessed by proton magnetic resonance spectroscopy ((1)H-MRS) in vivo. The study was designed to reveal the impact of pRT on normal brain tissue metabolism, which may potentially help in delineating the target volumes for reirradiated patients.Spectra of 43 patients ages 16-63 years treated with pRT for primary glial tumors in the Center of Oncology Maria Curie Memorial Institute Branch in Gliwice were analyzed. The control group consisted of spectra acquired for 30 healthy volunteers. All patients were treated with 3D conformal techniques using 6-20 MV photons to total doses of 60 Gy. Spectra were acquired from the control region before pRT and from three uninvolved regions 9-12 months after the end of pRT. Voxels were located in the region of low (6 Gy), medium (29-39 Gy), and high radiation dose ( approximately 60 Gy). Relative intensities of the signals relating to N-acetyl-aspartate (NAA), choline-based compounds, creatine and phosphocreatine (Cr), mio-Inositol, lactate, and lipids were obtained.The spectra of "normal brain" taken 9 months after pRT are significantly different from those obtained for control volunteers and from the spectra acquired before radiotherapy. The lactate and lipids signals are very strong; however, they are not correlated with absorbed dose. NAA/Cr ratios are significantly lower than before radiotherapy even for the low-dose regions. Differences increase with radiation dose: the NAA/Cr ratio is significantly lower for the regions of brain receiving a high dose of radiation than for the low-dose areas.Combined treatment of primary brain tumors (surgery + postoperative radiotherapy) causes alteration of brain metabolism, even in regions of the brain far from the postoperative tumor bed and receiving relatively low total doses of radiation. Single voxel MRS spectroscopy in vivo cannot help in delineating target volumes for secondary irradiation.

Purpose To study locoregional tumor control in postoperative radiotherapy (PRT) for head-and-neck cancer in relation to the position and duration of treatment gaps, duration of the interval surgery-radiotherapy, and to the other potentially prognostic variables. Methods and materials The retrospective study included 868 patients with cancer of the larynx, oral cavity, oropharynx, and hypopharynx treated in Gliwice between 1980 and 1997. Mean total radiation dose, dose per fraction, overall radiation treatment time (OTT), and the interval surgery-PRT were 62.8 Gy, 2.1 Gy, 45 days, and 63 days, respectively. No interruptions during PRT (except for weekend breaks) appeared in 30% of patients, whereas 19% had more than 5 days of gap. The actuarial locoregional recurrence-free survival (RFS) has been examined using multivariate Cox regression model, and the ultimate locoregional tumor control probability using a logistic model. Results Increased duration of treatment gaps, positive resection margins, pathologically proven metastases to the neck nodes, and extralaryngeal site of cancer were significantly related to a decrease in RFS. The duration of time interval surgery-PRT appeared, by contrast, only borderline significant for RFS. The relative risk of locoregional recurrence was approximately the same for the gaps in days 1–21 as for the “late” gaps (days >21), except in a subgroup of patients with positive clinical margins. The logistic analysis revealed a significant time-related displacement of the dose–response curves for PRT. The detriment from the protraction of OTT appeared to be larger than the benefit from the equivalent shortening of OTT. Conclusions Although the conclusions from this study must be regarded as only hypothesis-generating, we assume that a highly significant adverse influence of radiation treatment gaps on the rate of tumor control is consistent with rapid repopulation of cancer clonogenes during PRT. Lack of significant effect of the position of gaps on locoregional tumor control after radical surgery may suggest that a lag time for the onset of repopulation in PRT is short. A less likely explanation is that the total amount of regeneration during OTT is the same, regardless of the timing of the gap, even if all the repopulation occurred late. The magnitude of the detriment in tumor control from prolonged interval surgery-PRT indicates that repopulation of cancer cells between surgery and radiotherapy is not as fast as between the fractions of radiotherapy.

To investigate the individual pattern of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer who were treated with radiotherapy alone. Reactions were evaluated daily on an individual basis according to the Dische scoring system. Treatment of 87 head and neck cancer patients comprised either conventional fractionation- (CF; n = 33), accelerated fractionation (AF; n = 33), hyperfractionated- (HPEFX; n = 12) or hypofractionated (HPOFX; n = 9) radiotherapy with radical intent. Daily evaluation of AMRR progression was performed prospectively using a modified, morphologically functional Dische scoring system. The daily sums of the score parameters were subsequently used to construct an individual AMRR course curve for each patient. A latency period ranging from 3 to 14 days between the start of radiotherapy and the occurrence of the first AMRR symptom was observed in all patients. Based on the three different shapes of AMRR course curve observed during radiotherapy, three types of AMRR course can be described: (1) a continual increase in AMRR intensity until the completion of radiotherapy; (2) the incidence of a plateau phase following the increase in AMRR (increase–plateau course) and (3) decreasing AMRR intensity with a healing phase. A continual increase in AMRR intensity was observed in about 25 % of CF and AF patients and in more than 50 % of HPOFX treatments. This type of reaction was not observed in the HPEFX group. The increase–plateau course was noted in the majority of AF and CF patients; in almost half of those treated with HPOFX and in all HPEFX patients. A decreasing AMRR intensity course was observed in 23 % of all patients, although not observed at all in the HPEFX and HPOFX fractionation groups. The course of AMRR during radiotherapy can differ between individual patients. After the initial increase in AMRR intensity, a stabilization of the reaction—visible as a plateau phase on the course curve—is observed in the majority of patients. A proportion of the irradiated patients experience a continual increase in AMRR intensity up until the end of radiotherapy. A further group of patients exists in whom signs of AMRR healing are observed during the final stages of radiotherapy.

Purpose To report long-term results of randomized trial comparing 2 accelerated fractionations of definitive radiation therapy assessing the need to irradiate during weekend in patients with head and neck squamous cell carcinoma. Methods and Materials A total of 345 patients with SCC of the oral cavity, larynx, and oro- or hypo-pharynx, stage T2-4N0-1M0, were randomized to receive continuous accelerated irradiation (CAIR: once per day, 7 days per week) or concomitant accelerated boost (CB: once per day, 3 days per week, and twice per day, 2 days per week). Total dose ranged from 66.6-72 Gy, dose per fraction was 1.8 Gy, number of fractions ranged from 37-40 fractions, and overall treatment time ranged from 37-40 days. Results No differences for all trial end-points were noted. At 5 and 10 years, the actuarial rates of local-regional control were 63% and 60% for CAIR vs 65% and 60% for CB, and the corresponding overall survival were 40% and 25% vs 44% and 25%, respectively. Confluent mucositis was the main acute toxicity, with an incidence of 89% in CAIR and 86% in CB patients. The 5-year rate of grade 3-4 late radiation morbidity was 6% for both regimens. Conclusions Results of this trial indicate that the effects of accelerated fractionation can be achieve by delivering twice-per-day irradiation on weekday(s). This trial has also confirmed that an accelerated, 6-weeks schedule is a reasonable option for patients with intermediate-stage head-and-neck squamous cell carcinoma because of the associated high cure rate and minimal severe late toxicity.

The goal of this research was to evaluate the healing processes of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer. In 46 patients with oral and oropharyngeal cancer patients irradiated with conventional (n = 25) and accelerated (n = 21) dose fractionation AMRR was evaluated daily during and after radiotherapy. Complex of morphological and functional symptoms according to the Dische score were collected daily until complete healing. Duration of healing after the end of radiotherapy ranged widely (12–70 days). It was on the average 8 days longer for accelerated than for conventional radiotherapy (p = 0.016). Duration of dysphagia was also longer for accelerated irradiation (11 days, p = 0.027). Three types of morphological symptoms were observed as the last symptom at the end of AMRR healing: spotted and confluent mucositis, erythema, and edema. Only a slight correlation between healing duration and area of irradiation fields (r = 0.23) was noted. In patients with confluent mucositis, two morphological forms of mucosal healing were observed, i.e., marginal and spotted. The spotted form was noted in 71% of patients undergoing conventional radiotherapy and in 38% of patients undergoing accelerated radiotherapy. The symptoms of mucosal healing were observed in 40% patients during radiotherapy. The wide range of AMRR healing reflects individual potential of mucosa recovery with longer duration for accelerated radiotherapy. Two morphological forms of confluent mucositis healing were present: marginal and spotted. Healing of AMRR during radiotherapy can be observed in a significant proportion of patients.

The study aimed to detect features of human serum proteome that were associated with exposure to ionizing radiation. The analyzed group consisted of 46 patients treated with radical radiotherapy for larynx cancer; patients were irradiated with total doses in a range from 51 to 72 Gy. Three consecutive blood samples were collected from each patient: before the start, 2 weeks after the start, and 4-6 weeks after the end of radiotherapy. The low-molecular-weight fraction of the serum proteome (2,000-13,000 Da) was analyzed by the MALDI-ToF mass spectrometry. Proteome profiles of serum samples collected before the start of radiotherapy and during the early stage of the treatment were similar. In marked contrast, mass profiles of serum samples collected several weeks after the end of the treatment revealed clear changes. We found that 41 out of 312 registered peptide ions changed their abundance significantly when serum samples collected after the final irradiation were compared with samples collected at the two earlier time points. We also found that abundances of certain serum peptides were associated with total doses of radiation received by patients. The results of this pilot study indicate that features of serum proteome analyzed by mass spectrometry have potential applicability as a retrospective marker of exposure to ionizing radiation.

The plasma proteome was analysed as a potential source of markers of radiosensitivity in patients treated with definitive radiotherapy for head and neck cancer.Acute mucosal reactions that developed during radiotherapy were assessed in 55 patients. Blood samples were collected from each patient before the treatment and also from 50 healthy donors. The low-molecular-weight fraction of the plasma proteome (2,000-10,000 Da range) was analysed by the Matrix-Assisted Laser Desorption Ionisation mass spectrometry. The capacity for DNA break repair was assessed by the comet assay using lymphocytes irradiated in vitro.Spectral components registered in plasma samples were used to build classifiers that discriminated patients from healthy individuals with about 90% specificity and sensitivity (components of 4469, 6929 and 8937 Da were the most essential for cancer classification). Four spectral components were identified (2219, 2454, 3431 and 5308 Da) whose abundances correlated with a maximal intensity of the acute reaction. Several spectral components whose abundances correlated with the rate of DNA repair in irradiated lymphocytes were also detected. Additionally, a more rapid escalation of an acute reaction was correlated with a higher level of unrepaired damage assessed by the comet assay. conclusions: The plasma proteome could be considered as a potential source of predictive markers of acute reaction in patients with head and neck cancer treated with radiotherapy.

Purpose To evaluate severity of acute mucosal reactions (AMR) caused by conventional (CF) and accelerated fractionation (AF) regimens using a modified Dische system and to analyze differences in incidence and severity of AMR according to frequency and regularity of scoring. Methods and Materials Sixty-six consecutive patients (33 CF, 33 AF) with head and neck cancer irradiated with 5 fractions in 5 days per week (CF) or with 7 fractions in 7 days (AF) to a total dose of 70 Gy. A modified Dische system was used for daily quantitation of AMR during radiotherapy until complete healing. Results Confluent mucositis (CM) was noted in 79% of patients in the CF group and 85% in the AF group. In 24% of the CF group and 18% of the AF group the CM presented a wave-like pattern. In 55% of CF and 67% of AF a classic triphasic pattern was noted. In 12 patients acute reactions did not transgress the level of spotted mucositis. The present study clearly shows that quantitation of the incidence and severity of acute mucosal effects strongly depends on frequent and regular scoring. A significant difference in the incidence of CM between the CF and AF groups was noted, mainly in weeks 4–6 of irradiation. When once-weekly irregular instead of daily scoring was evaluated, the incidence of CM was underestimated by approximately 20–36%. Conclusions Acute mucosal reactions occur as a complex of morphologic and functional disorders with individual intensity, even among patients treated with the same fractionation regimen. In some cases they present a “wave-like” pattern during irradiation. Therefore, precise quantitation of acute effects requires regular and frequent scoring.

Purpose To investigate the prognostic value of hemoglobin (Hb) concentration in patients with laryngeal cancer treated with postoperative radiotherapy (pRT). Methods and Materials The records of 835 patients who underwent pRT between 1980 and 2003 were reviewed. Most patients (526 of 835 patients; 63%) were in advanced clinical stages (T3–T4) and 371 of 835 patients (44%) were node positive. Total laryngectomy had been performed in 676 of 835 patients (81%). Median Hb concentration before (Hb0) and after pRT (Hb1) was the same (13.3 g/dl). However, individual differences between Hb1 and Hb0 (dHb) varied within a broad range (−8.8; 5.0 g/dl). Univariate and multivariate analyses were performed to identify variables significantly associated with locoregional control (LRC), metastases-free survival, and overall survival. Results Patients with dHb greater than 0 had significantly improved 5-year LRC compared with those with dHb of 0 or less (80% vs. 72%, p = 0.01). Conversely, when categorized, neither Hb0 nor Hb1 had a significant influence on LRC. In multivariate analysis, dHb remained a prognostic factor for LRC ( p = 0.01) among the other variables, which included overall radiation treatment time and nodal status. None of the Hb-related variables significantly influenced metastases-free or overall survival. Conclusion Individual change in Hb concentration during the course of pRT (dHb) rather than Hb level before or after pRT appeared as an independent prognostic factor for LRC in this set of patients.

CelPrzedstawienie wyników łeczenia skojarzonego chorych na nowotwory jamy ustnej w ramach Zespołu Narządowego Nowotworów Głowy i Szyi w latach 1995 – 2000 w Instytucie Onkologii w Gliwicach.MaterialPodmiotem analizy jest grupa 102 chorych; 70 (69%) mężczyzn i 32 (31%) kobiet w średnim wieku 54 lat chorych na raka jamy ustnej leczonych za pomocą chirurgii i pooperacyjnej radioterapii. Najczęstsza lokalizacją guza pierwotnego była część ruchoma języka i dno jamy ustnej oraz wyrostek zębodołowy żuchwy odpowiednio 48 (47%) i 27 (26%) chorych, a rozpoznanie raka płaskonabłonkowego postawiono w 93 (92%) przypadkach. Zaawansowanie guza pierwotnego postawione na podstawie badania klinicznego oraz metod obrazowych ustalono w największym odsetku jako T2 oraz T3; odpowiednio 41 (40%) i 33 (34%) chorych. U 42 (41%) chorych nie stwierdzono przerzutowo zmienionych węzłów chłonnych, a w 31 (30%) przypadkach zanotowano pojedyncze (N1) przerzuty do węzłów chłonnych szyi. U 26 (25%) chorych wykonano zabieg miejscowy usunięcia guza z marginesem zdrowych tkanek, u pozostałych 76 (75%) zabieg blokowy obejmujące ognisko pierwotne jak i węzły chłonne. Mikroskopowa radykałność leczenia chirurgicznego została potwierdzona w 55 (54%) przypadków, a średnia szerokość ocenionych w preparatach pooperacyjnych marginesów wyniosła 3.8 mm, przy średnio 3 ocenionych marginesach. Wszyscy chorzy poddani zostali pooperacyjnej radioterapii, którą rozpoczynano 56 dni po zabiegu. W 87 (86%) przypadkach zastosowano konwencjonalne frakcjonowanie dawki, u pozostałych frakcjonowanie przyśpieszone, do średniej dawki całkowitej 66. 6 Gy. 101 (99%) chorych zakończyło leczenie zgodnie z planem. Średni całkowity czas leczenia skojarzonego wyniósł 100 dni, a mediana okresu obserwacji 5 lat.Wyniki5-letnie odsetki wyleczeń miejscowych, przeżyć bezobjawowych oraz ca łkowitych wyniosło odpowiednio: 87%, 72% oraz 70%. Ana łiza jednowariantowa wykazała, iż zaawansowanie guza pierwotnego (T4) związane było ze znamiennie niższym prawdopodobieństwem wyleczenia miejscowego, a niekonwencjonalne frakcjonowanie dawki z obniżeniem odsetka przeżyć bezobjawowych (p

HRZ3.51, 95% CI: 1.56-7.90, pZ0.001). Interrogation of The Cancer Genome Atlas database for HNSCC samples with both methylation and outcome data available (nZ305), revealed a similarly absent or low frequency of methylation events for the loci investigated. However, the presence of RUNX3 hypermethylation did not correlate with worse outcome for patients (HR Z 1.27; 95% CI: 0.56 2.88; pZ0.57 and HR Z 1.08; 95% CI: 0.65 1.82; p Z0.76, OTSCC and HNSCC, respectively). Conclusion: In OTSCC, we found little evidence of promoter hypermethylation of genes previously reported to be frequently methylated in HNSCC. Whilst OTSCC may have subsite-specific methylation for the loci examined, it is likely that previously reports have overestimated methylation events with the use of non-quantitative methodology. Author Disclosure: A.M. Lim: None. I.L.M. Candiloro: None. N. Wong: None. M. Collins: None. H. Do: None. C. Angel: None. J. Corry: None. D. Rischin: None. B. Solomon: None. A. Dobrovic: None.