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Introduction. The paper presents an original, used in our Institute, method of lung volume irradiation in patients with pneumonia during COVID-19 infection. Material and methods. Procedures such as the simulation of treatment and radiotherapy are performed in a treatment room. Real time radiation treatment planning is realized as 2D planning (Irreg Planning VMS) in a separate room, and the 3D (eclipse VMS) dose distribution is calculated after the treatment. During radiation exposure, a fluence map is measured. Results. A method of irradiating the lungs of patients with COVID-19 was developed, which allows to shorten the time the patient is on the treatment table and minimize contacts between the patient and staff. Conclusions. The presented procedure made it possible to minimize the time of patient’s stay in the radiotherapy department and at the same time, it retains all the required quality assurance procedures in radiotherapy treatment.

Head and neck cancer is a serious clinical and social problem. Surgery and radiotherapy play the most important role in treatment and give the chance of cure. Optimal treatment of patients with head and neck cancer should provide for the maximum destruction of cancerous tissue, saving as much healthy tissue as possible. Despite this, due to radiotherapy still almost 90% of patients develop skin symptoms. It seems that the mechanism of radiodermatitis is quite clear, but studies assume that its pathogenesis is not fully understood and there is much to be clarified. Acute and chronic dermatitis caused by radiotherapy is usually diagnosed according to clinical criteria. It seems that it would be useful to have a photographic classification that would facilitate and unify the clinical evaluation. In this article we shall summarize the current knowledge about the mechanisms of formation, risk factors, clinical classifications and methods for the prevention and treatment of acute and chronic radiation dermatitis. We have included clinical photos that depict individual stages according to the clinical classification of RTOG.

State-of-art normal tissue complication probability (NTCP) models do not take into account more complex individual anatomical variations, which can be objectively quantitated and compared in radiomic analysis. The goal of this project was development of radiomic NTCP model for radiation-induced hypothyroidism (RIHT) using imaging biomarkers (radiomics). We gathered CT images and clinical data from 98 patients, who underwent intensity-modulated radiation therapy (IMRT) for head and neck cancers with a planned total dose of 70.0 Gy (33–35 fractions). During the 28-month (median) follow-up 27 patients (28%) developed RIHT. For each patient, we extracted 1316 radiomic features from original and transformed images using manually contoured thyroid masks. Creating models based on clinical, radiomic features or a combination thereof, we considered 3 variants of data preprocessing. Based on their performance metrics (sensitivity, specificity), we picked best models for each variant ((0.8, 0.96), (0.9, 0.93), (0.9, 0.89) variant-wise) and compared them with external NTCP models ((0.82, 0.88), (0.82, 0.88), (0.76, 0.91)). Our models reach accuracy comparable with or better than previously presented non-radiomic NTCP models. The benefit of our approach is obtaining the RIHT predictions before treatment planning to adjust IMRT plan to avoid the thyroid region in most susceptible patients.

Several immune and hematological parameters are associated with survival in patients with oropharyngeal cancer (OPC). The aim of the study was to analyze selected immune and hematological parameters of patients with HPV-related (HPV+) and HPV-unrelated (HPV-) OPC, before and after radiotherapy/chemoradiotherapy (RT/CRT) and to assess the impact of these parameters on survival. One hundred twenty seven patients with HPV+ and HPV− OPC, treated with RT alone or concurrent chemoradiotherapy (CRT), were included. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (Formalin-Fixed, Paraffin-Embedded) tissue samples and/or extracellular circulating HPV DNA was determined. The pre-treatment and post-treatment laboratory blood parameters were compared in both groups. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune inflammation (SII) index were calculated. The impact of these parameters on overall (OS) and disease-free (DFS) survival was analyzed. In HPV+ patients, a high pre-treatment white blood cells (WBC) count (&gt, 8.33 /mm3), NLR (&gt, 2.13), SII (&gt, 448.60) significantly correlated with reduced OS, whereas high NLR (&gt, 2.29), SII (&gt, 462.58) significantly correlated with reduced DFS. A higher pre-treatment NLR and SII were significant poor prognostic factors for both OS and DFS in the HPV+ group. These associations were not apparent in HPV− patients. There are different pre-treatment and post-treatment immune and hematological prognostic factors for OS and DFS in HPV+ and HPV− patients. The immune ratios could be considered valuable biomarkers for risk stratification and differentiation for HPV− and HPV+ OPC patients.

Nasopharyngeal cancer (NPC) is highly prevalent in southern Chinese populations but it is rare in most parts of the world. A few studies were performed in nonendemic regions of the world, and suggested the prognostic value of Epstein-Barr virus (EBV) DNA load in blood. In this study, EBV DNA presence and viral load (VL) level in the blood of patients with NPC in Polish population were presented. In addition, its prognostic value for locoregional control among other clinicopathological features was evaluated. Patients with carcinoma of the nasopharynx treated definitively with radiotherapy or radiochemotherapy were included in the study. Real-time polymerase chain reaction was performed for quantitating of EBV DNA in plasma. Among patients with NPC, 51% (22 of 43) were classified as EBV-positive with the mean of the VL of 4934 ± 8693 copies/mL. Multiple regression analysis between log EBV DNA VL and clinical parameters revealed that the most important factors increasing the VLs were advanced N disease together with no-smoking status and advanced T tumors. Multivariate Cox regression analysis revealed that T3-T4 tumors were an independent prognostic factor for poor locoregional control. Analysis for the subgroup of patients with T1-T2 tumors showed that T1-T2 EBV-negative patients had better locoregional control compared with T1-T2 EBV-positive, though without statistical significance. In conclusion, it seems that EBV DNA determination may have an important role in diagnostics of patients with NPC with T1-T2 tumors indicating a subgroup with poorer prognosis, though it needs to be proven on a larger cohort.

Introduction Carcinoma of unknown primary site (CUP) refers to 1-5% of all head and neck neoplasms. Very often, the primary site remains difficult to determine. Squamous cell carcinoma is the most frequent histopathological type diagnosed in the head and neck region. According to statistics, a primary site is usually located in the oropharynx. Study objective The study presents diagnostic difficulties and the methods of diagnosing and the therapy of CUP and primary sites in patients treated in the region of Lower Silesia and Silesia. The aim of the study was to show a retrospective analysis of 233 CUP patients to assess how clinical features, diagnosis and treatment affect the survival of patients. Material and methods The diagnostics of patients included panendoscopy with specimen collection (nasoendoscopy, laryngoscopy, esophagoscopy, brochoscopy), computed tomography examination of the neck, chest, abdomen and pelvis minor, as well as positron emission tomography examination. Tonsilletomy was performed in 37 patients. Neck dissection was carried out in 109 subjects and 165 patients were treated bt radiotherapy, and 135 by chemotherapy. Conclusions Tonsillectomy is required in CUP patients with the negative results of biopsy and imaging tests. It gives a possibility of detecting the primary site and improves the results of treatment and survival of CUP patients.Combination therapy, including surgical treatment and chemoradiotherapy, gives the best therapeutic results in CUP patients. The general condition of patient and younger age have an impact on prognosis and survival.

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.

Simple Summary Hypothyroidism is a common complication of therapeutic irradiation in the neck area. Several dose-response models have been proposed to predict its’ occurrence based on clinical and radiomic features. We aimed to externally validate the results of five such models in a prospectively recruited cohort of 108 patients with oropharyngeal cancer. Two of the evaluated models, published by Rønjom et al. and by Boomsma et al., had satisfactory performance. Both models are based on mean thyroid dose and thyroid volume. Three remaining models, by Cella et al., Bakhshandeh et al. and Vogelius et al., performed significantly worse. Short-term change in the level of thyroid-stimulating hormone (TSH) after radiation therapy was not indicative of hypothyroidism development in long term. We conclude that the models by Rønjom et al. and by Boomsma et al. are feasible for long-term prediction of hypothyroidism in oropharyngeal cancer survivors treated with intensity-modulated radiation therapy. Abstract We aimed to externally validate five normal tissue complication probability (NTCP) models for radiation-induced hypothyroidism (RIHT) in a prospectively recruited cohort of 108 patients with oropharyngeal cancer (OPC). NTCP scores were calculated using original published formulas. Plasma thyrotropin (TSH) level was additionally assessed in the short-term after RT. After a median of 28 months of follow-up, thirty one (28.7%) patients developed RIHT. Thyroid mean dose and thyroid volume were significant predictors of RIHT: odds ratio equal to 1.11 (95% CI 1.03–1.19) for mean thyroid dose and 0.87 (95%CI 0.81–0.93) for thyroid volume in univariate analyses. Two of the evaluated NTCP models, published by Rønjom et al. and by Boomsma et al., had satisfactory performance with accuracies of 0.87 (95%CI 0.79–0.93) and 0.84 (95%CI: 0.76–0.91), respectively. Three remaining models, by Cella et al., Bakhshandeh et al. and Vogelius et al., performed significantly worse, overestimating the risk of RIHT in this patient cohort. A short-term TSH level change relative to baseline was not indicative of RIHT development in the follow-up (OR 0.96, 95%CI: 0.65–1.42, p = 0.825). In conclusion, the models by Rønjom et al. and by Boomsma et al. demonstrated external validity and feasibility for long-term prediction of RIHT in survivors of OPC treated with Intensity-Modulated Radiation Therapy (IMRT).

Angiogenesis is essential for growth, progression, and metastasis of solid tumors. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) and angiopoietin (ANGPT)/ tyrosine kinase endothelial (TEK) signaling plays an important role in regulating angiogenesis. Very little is known about the effects of single-nucleotide polymorphisms (SNPs) in angiogenesis-related genes on treatment outcome in head and neck squamous cell carcinoma (HNSCC). Therefore, we evaluated the association between SNPs in ANGPT1, ANGPT2, TEK, VEGF, VEGFR1, and VEGFR2 genes and five clinical endpoints in 422 HNSCC patients receiving radiotherapy alone or combined with chemotherapy. Multivariate analysis showed an association of ANGPT2 rs3739391, rs3020221 and TEK rs639225 with overall survival, and VEGF rs2010963 with overall and metastasis-free survival. VEGFR2 rs1870377 and VEGF rs699947 affected local recurrence-free survival in all patients. In the combination treatment subgroup, rs699947 predicted local, nodal, and loco-regional recurrence-free survival, whereas VEGFR2 rs2071559 showed an association with nodal recurrence-free survival. However, these associations were not statistically significant after multiple testing correction. Moreover, a strong cumulative effect of SNPs was observed that survived this adjustment. These SNPs and their combinations were independent risk factors for specific endpoints. Our data suggest that certain germline variants in ANGPT2/TEK and VEGF/VEGFR2 axes may have predictive and prognostic potential in HNSCC treated with radiation or chemoradiation.

Background Early detection of treatment failure may improve clinical outcome and overall survival in patients with head and neck cancer after first-line treatment. Circulating cell-free HPV16 DNA (cfHPV16 DNA) was evaluated as a possible complementary marker to radiological assessment of early response in patients with HPV-related oropharyngeal cancer (OPC) after radiotherapy alone or combined with chemotherapy. Methods The study included 66 patients with HPV-related OPC receiving radical radiotherapy alone or in combination with chemotherapy. cfHPV16 DNA was assessed in the blood of all patients before treatment using TaqMan-based qPCR. Subsequent analysis of cfHPV16 DNA was performed 12 weeks after treatment completion, along with radiological assessment of early treatment results. Results Complete (CRR) and incomplete radiological response (IRR) was found in 43 (65%) and 23 (35%) patients respectively. cfHPV16 DNA was present in 5 (28%) patients with IRR, while only in 1 (4%) with CRR. Three of five patients with IRR that were positive for cfHPV16 DNA exhibited histopathologically confirmed local or regional treatment failure, and other two developed distant metastases. None of the patients with negative cfHPV16 DNA presented disease failure. Conclusion The post-treatment assessment of cfHPV16 DNA in patients with HPV-related OPC may be used as a complementary biomarker to conventional imaging-based examinations for early identification of treatment failure.

Anticancer treatment induces systemic molecular changes that could be detected at the level of biofluids. Understanding how human metabolism is influenced by these treatments is crucial to predict the individual response and adjust personalized therapies. Here, we aimed to compare profiles of metabolites in serum of head and neck cancer patients treated with concurrent chemo-radiotherapy, radiotherapy alone, or induction chemotherapy. Serum samples were analyzed by a targeted quantitative approach using combined direct flow injection and liquid chromatography coupled to tandem mass spectrometry, which allowed simultaneous quantification of 149 metabolites. There were 45 metabolites whose levels were significantly changed between pretreatment and within- or post-treatment serum samples, including 38 phospholipids. Concurrent chemo-radiotherapy induced faster and stronger effects than radiotherapy alone. On the other hand, chemotherapy alone did not result in significant changes. The decreased level of total phospholipids was the most apparent effect observed during the first step of the treatment. This corresponded to the loss of patients’ body mass, yet no correlation between both parameters was observed for individual patients. We concluded that different molecular changes were measured at the level of serum metabolome in response to different treatment modalities.

Paragangliomas of the head and neck are a group of neoplasms which occur very rarely. Most of them are benign tumours. Tinnitus, headaches and dysfunction of the cranial nerves are typical symptoms. Some paragangliomas have metastatic abilities and they can produce catecholamines. There are some typical imaging features in CT and MRI scans which help to determine the correct diagnosis without the necessity of performing a biopsy which can be associated with a haemorrhage risk. Therapeutic management consists of the choice between an active observation, surgical procedure, as well as radiotherapy and systemic therapy in the case of malignant paragangliomas.

Purpose: There is a lack of effective diagnostic tools for early assessment of radiotherapy (RT) outcome in patients with head and neck cancer (HNC). The timely diagnosis of treatment failure may facilitate use of salvage procedures to prevent disease progression. We assessed squamous cell carcinoma antigen and CYFRA 21-1 as early markers of radiotherapy failure in patients with HNC. Methods: Between January 2009 and February 2012, 185 patients (median age 59 years) with squamous cell carcinoma were treated with curative intent with RT alone or combined with chemotherapy (ChT). Markers were estimated in the serum 2 times: before RT and after completion of treatment. Results: The median of follow-up was 40 months. Locoregional control (LRC) was 53% and locoregional failure (LRF) was 31%. When comparing LRC and LRF, there were no significant differences between markers concentration obtained before RT. After RT, CYFRA 21-1 (p = 0.018) was significantly elevated in the LRF group. Patients with CYFRA 21-1 Conclusions: CYFRA 21-1 assessed at the end of RT or ChT seems to be a prognostic marker for tumor response. A high concentration of CYFRA 21-1 after treatment increases the risk of death. CYFRA 21-1 might be suggested in the monitoring of carcinomas of HNC.

State-of-art normal tissue complication probability (NTCP) models do not take into account more complex individual anatomical variations, which can be objectively quantitated and compared in radiomic analysis. The goal of this project was development of radiomic NTCP model for radiation-induced hypothyroidism (RIHT) using imaging biomarkers (radiomics). We gathered CT images and clinical data from 98 patients, who underwent intensity-modulated radiation therapy (IMRT) for head and neck cancers with a planned total dose of 70.0 Gy (33–35 fractions). During the 28-month (median) follow-up 27 patients (28%) developed RIHT. For each patient, we extracted 1316 radiomic features from original and transformed images using manually contoured thyroid masks. Creating models based on clinical, radiomic features or a combination thereof, we considered 3 variants of data preprocessing. Based on their performance metrics (sensitivity, specificity), we picked best models for each variant ((0.8, 0.96), (0.9, 0.93), (0.9, 0.89) variant-wise) and compared them with external NTCP models ((0.82, 0.88), (0.82, 0.88), (0.76, 0.91)). We showed that radiomic-based models did not outperform state-of-art NTCP models (p &gt, 0.05). The potential benefit of radiomic-based approach is that it is dose-independent, and models can be used prior to treatment planning allowing faster selection of susceptible population.

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).

Malnutrition is a common problem in patients with head and neck cancer (HNC), including oropharyngeal cancer (OPC). It is caused by insufficient food intake due to dysphagia, odynophagia, and a lack of appetite caused by the tumor. It is also secondary to the oncological treatment of the basic disease, such as radiotherapy (RT) and chemoradiotherapy (CRT), as a consequence of mucositis with the dry mouth, loss of taste, and dysphagia. The severe dysphagia leads to a definitive total impossibility of eating through the mouth in 20–30% of patients. These patients usually require enteral nutritional support. Feeding tubes are a commonly used nutritional intervention during radiotherapy, most frequently percutaneous gastrostomy tube. Recently, a novel HPV-related type of OPC has been described. Patients with HPV-associated OPC are different from the HPV− ones. Typical HPV− OPC is associated with smoking and alcohol abuse. Patients with HPV+ OPC are younger and healthy (without comorbidities) at diagnosis compared to HPV− ones. Patients with OPC are at high nutritional risk, and therefore, they require nutritional support in order to improve the treatment results and quality of life. Some authors noted the high incidence of critical weight loss (CWL) in patients with HPV-related OPC. Other authors have observed the increased acute toxicities during oncological treatment in HPV+ OPC patients compared to HPV− ones. The aim of this paper is to review and discuss the indications for nutritional support and the kinds of nutrition, including immunonutrition (IN), in HNC, particularly OPC patients, undergoing RT/CRT, considering HPV status.

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.

6069 Background: New therapeutic approaches are needed for elderly or frail head and neck squamous cell carcinoma (HNSCC) patients (pts) ineligible for standard of care treatment. NBTXR3, a crystalline solution of hafnium oxide nanoparticles may represent such an option. Injected intratumorally, NBTXR3 enters tumor cells and yields an increased cell-localized energy deposit upon exposure to radiotherapy (RT), leading to increased tumor cell death compared to the same dose of RT alone. Methods: Phase I study of NBTXR3 activated by RT in pts ≥70 years old or ≥65 years old and unable to receive cisplatin, eligible for exclusive RT with stage III or IV HNSCC of the oral cavity or oropharynx [NCT01946867]. A 3+3 dose escalation design was implemented with dose levels corresponding to 5%, 10%, 15% and 22% of baseline tumor volume, followed by an expansion phase. Pts received an intratumoral (IT) injection of NBTXR3 and intensity modulated RT (IMRT; 70 Gy/35 fractions/7 weeks). Determination of Recommended Phase 2 Dose (RP2D) and Dose Limiting Toxicities (DLT) were primary endpoints of phase I. Absence of NBTXR3 leakage and preliminary efficacy using RECIST 1.1 principles were also evaluated. Results: The dose-escalation is complete. Nineteen pts were enrolled: 3 at 5%, 3 at 10%; 5 at 15% and 8 at 22% with no observed DLT or SAE related to NBTXR3 or IT injection. One grade 1 NBTXR3-related AE (asthenia at 22%) and four IT injection-related AE (grade 2 oral pain; grade 1 tumor hemorrhage; grade 1 asthenia, and grade 1 injection site hemorrhage) were reported. RT-related toxicity was as expected with IMRT. RP2D has been determined to be 22%. CT-scan assessment between 24h and 7 weeks post-IT injection demonstrated absence of NBTXR3 leakage in the surrounding tissues. Among 13 evaluable pts treated at doses ≥10%, 9 achieved a complete response of the injected lesion. Conclusions: These results show that NBTXR3 activated by RT is safe and well tolerated at all doses with preliminary encouraging efficacy results. It thus represents a promising future treatment for frail and elderly pts with locally advanced HNSCC with limited therapeutic options. Expansion phase has started at the RP2D. Clinical trial information: NCT01946867.

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.

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.

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.

Squamous cell carcinoma is an extremely rare neoplasm of the thyroid (SCTC) that represents no more than 1% of all primary thyroid malignancies. We report a case of a 42-year-old woman with rapidly growing mass in the right lower neck, primarily diagnosed in fineneedle aspiration cytology as a low-differentiated carcinoma. After the surgery, exclusion of all the other possible primary tumour locations, and immunohistochemistry tests, the diagnosis of primary squamous cell carcinoma of the thyroid gland was established. Because of close surgical margins and metastatic neck node, the patient was referred to adjuvant postoperative irradiation. With five-year follow-up the patient is free of disease and still in very good condition.

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 decision regarding treatment of early supraglottic carcinoma remains controversial. Single institution clinical data of patients with T2 supraglottic carcinoma treated exclusively with radiotherapy in terms of prognostic factors and treatment results were analyzed. Patient-related factors that would potentially by useful for optimal therapeutic decision to be undertaken were especially investigated. Between 1994 and 2004, 78 patients with T2 supraglottic carcinoma underwent radiotherapy (RT) in Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Poland. There were 54 (69%) males and 24 (31%) females in the median age of 61 years. There were 17 (22%) patients with N+. Median body mass of patients before (BM0) and after RT (BM1) was 74 kg (range 45.2–130 kg) and 72.9 kg (range 49.9–122.5 kg), respectively. Median hemoglobin concentrations before (Hb0) and after (Hb1) RT were 14.3 and 13.4 g/dl, respectively. Median change of Hb concentration during RT (dHb) was −0.8 g/dl. All were treated up to total doses (TD) ranged from 62.5 to 72 Gy. The overall treatment time (OTT) ranged from 30 to 70 days. Estimates of local control (LC), ultimate local control (uLC), and overall survival (OS) were calculated using the Kaplan–Meier method. Log rank statistics, Cox proportional hazard model and step-wise Cox regression hazard model were employed to identify prognostic factors for LC, uLC, and OS in univariate and multivariate analyses. The 5-year LC, RC, uLC and OS rates were 85, 92, 88, and 56%, respectively. In multivariate analysis N+ (p = 0.01) and prolonged OTT (p = 0.03) significantly decreased LC. Females (p = 0.02), higher BM0 (p = 0.03), and HB0 (p = 0.006) significantly prolonged OS. Patient-related factors like gender, hemoglobin concentration, and body mass may predict treatment outcome. Radiotherapy is effective for T2 supraglottic carcinoma of the larynx unless higher dose intensity is provided. Involved regional lymph nodes significantly deteriorate locoregional cure.

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.

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.

Alm Endobronchial HDR brachytherapy (E-HDR-BT) is a well-established method of palliative treatment in patients with lung cancer. There is, however, no consensus on optimal radiation and the rate of complications. The aim of the work is to evaluate early effectiveness and tolerance of E-HDR-BT in palliative treatment of patients with lung cancer treated in Oncology Centre in Gliwice. Material and methods Since 2000 in Oncology Centre in Gliwice HDR (Ir192) E-HDR-BT is used in palliative treatment of patients with bronchial obturation due to lung cancer. Regression of bronchial obturation and improvement in dyspnoea, cough and haemoptysis after therapy was analyzed for the first thirty patients. The total dose was 18 Gy, calculated at 1cm from the source, in 3 fraction (of 6 Gy) given everyweek. Results Twenty-five patients finished therapy as planned. Five patients didn’t complete treatment: two of them (6.6%) died because of massive haemoptysis; one patients suffered from exaggeration of angina pectoris, one patients developed high hectic fever not responding for antibacterial treatment, one suffered from exaggeration of their symptoms prohibiting continuation of the treatment. Changes in obturation of the bronchi and in patient's symptoms are shown in Table 1 . Table 1 . Changes in obturation of the bronchi and in patient's symptom. Symptoms Improvement Nochanges Exaggeration Obturation #/% 22/88% 3/12% 0 Dyspnoea #/% 15/54% 11/40% 2/7% Cough #/% 4/27% 10/67% 2/7% Haemoptysis #/% 2/14% 10/72% 2/14% More detailed analysis of improvements in symptoms has been carried out according to own scoring system for dyspnoea, cough and haemoptysis. Mean duration of palliative response was 55 days (1–405). Mean survival time was 114 days (2–406). Conclusion E-HOR-BT is an effective method of palliation of symptoms related to bronchial obturation in course of lung cancer. The most frequent serious treatment complication of E-HOR-BTwas massive haemoptysis.

Background & Aim Our experience with CAIR fractionation, recognized as an effective organ preservation treatment for moderately advanced head and neck cancer, have induced us to idea on concomitant combination of continuous radiotherapy (7 fractions in 7 days) with chemotherapy, dedicated for advanced, stage III and IV, patients. This report evaluates early results of toxicity and cure of patients treated during the years 1999–2003. Material 47 male patients with median age 51 years were prospectively evaluated-36 patients (77%) with stage IV and 11 (23%) with stage III. Oropharynx was the most freaquent tumour location-16 patients (34%). Chemotherapy, four cycles of cisplatinum and vinorelbin given in 1-day schedule, started on the day 1st, each 21 days. CAIR-scheme radiotherapy started on the 22nd day to the total dose of 68Gy. Compliance to the RT protocol was 98%. During the first year 57% of patients completed 4 courses of chemo, 11 (24%)-3 cycles and 9 (19%)-2 courses. After reduction the doses of cisplatinum (100 to 70 mg/m 2 ) and vinorelbine (30 to 20 mg/m 2 ) chemotherapy was conducted with at least 3 cycles. One patient died because the treatment toxicity. All patients developed confluent mucositis lasted medially 60 days. Grade IV and III of leucopenia were found in 4 (8%) and 15 (32%) patents. Median follow up was 446 days (ranged from 7 to 1486 days). Results CR was observed in 38 (81%) patients. The rates of LC, DSF and OS were 81%, 62% and 80% respectively after 2 years. On univariate analysis N3 stage was significantly associated with decreased rates of all survival criteria; the higher LC and DSF rates were also found for patients receiving all 4 courses of chemotherapy and with egzophitic tumour-growth pattern. Multivariate analysis revealed that N3 stage and necrosis in metastatic Iymph nodes were the idependent negative prognostic factors influencing LC and DSF. Conclusions Chemo-CAIR produces promising early results of cancer cure. Treatment toxicity is high, but satisfactorily tolerated and did not affect the ability to deliver planned doses of radiotherapy. The most important factor affected treatment outcome were N3 stage and necrosis in Iymphatic nodes.

Because Docetaxel has both radiosensitizing properties as well as good anticancer activity by itself in squamous cell carcinomas we are going to attempt concurrent use of Docetaxel and radiochemiotherapy in patients with advanced head and neck cancers (HNC). Aim The objective of this study is to evaluate the response rate, loco-regional control, disease – free survival and overall survival in previously untreated inoperable HNC patients. Methods This is a project of an open non-randomized, one centre, phase II, one arm study. Total planned dose of RT for GTV is 68 Gy given in 40 fractions, once daily, 7 times per week concomitantly with Cis-Platin, Navelbine and Docetaxel. Eligibility criteria include: proven HNC not treated before, good performance status, normal bone marrow, liver and renal function, age bellow 60. The regimen is proposed as follows: Cis-Platin i.v. 70 mg/m 2 on day 1, 22, 43, 64, Navelbine 20 mg/m 2 i.v. on day 1, 8, 22, 29, 43, 50, 64 and Docetaxel 30 mg/m 2 /week or as 1-h infusion of 60 mg/m 2 in each 7 days of RT, Ethyol 1000 mg i.v. on day 1, 22, 43 and 250 mg on day 23–42. Radiotherapy 1,7 Gy per fraction continuously on day 23–42 and 44–63. Different treatment schedules of Docetaxel could be used on the basis of cellular activity for a given tumour. So, biopsy should be obtained for analysis of pretreatment levels of apoptosis and oncogenes such as p53, Bax, Bcl-2.