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Objectives The aim of the study was to evaluate the long-term outcome and late effects in pediatric patients with nasopharyngeal carcinoma (NPC) treated with neoadjuvant chemotherapy (NACT), followed by radiotherapy (RT). Methods Ninety-two children (65 male, 27 female) diagnosed with NPC between 1989 and 2017 in the Istanbul University, Institute of Oncology were evaluated retrospectively. NACT consisted of three cycles of cisplatin-containing regimen every 3 weeks, followed by RT. Results The median age was 13 years (5-18 years). Most had locoregionally advanced disease (stage III/IVA/IVB) and five had distant metastases at presentation. At a median follow-up of 108 months (3-332 months), 5- and 10-year overall survival rates and event-free survival rates were 87.5%, 79.7% and 82.1%, 78.9%, respectively. Three patients with distant metastasis are long-term survivors. Thirteen patients relapsed at a median of 8 months (2-23 months). Hypothyroidism (36%) and xerostomia (25%) were the most frequent long-term treatment-related toxicities. Nine second malignancies developed in eight patients, eight in the irradiated field at a median of 14 years (range 5-26 years), five of whom are long-term survivors after curative surgery. Conclusions Three courses of cisplatin-containing NACT, followed by RT lead to high survival and locoregional control rate in advanced stage NPC in children. Patients with distant metastasis should also be treated with curative intent by systemic chemotherapy and locoregional radiotherapy. Patients should be followed closely for recurrences and long-term morbidities including second malignancies, which may be treated with curative surgeries if diagnosed early.

OBJECTIVE The present study aims to compare the treatment plan parameters of different radiotherapy techniques {[}3D-Conformal Radiotherapy (3D-CRT), Dynamic - Intensity Modulated Radiotherapy (D-IMRT), Intensity Modulated Arc Therapy (IMAT) and Helical Tomotherapy (HT)] in Early-Stage Glottic Larynx (EGL) cancer to increase the treatment dose from 63 Gy to 70 Gy. METHODS The dose prescription was defined as 2.12 Gy per fraction to a total of 33 fractions. 95\% of Planning Treatment Volume-63 Gy (PTV-63) and Planning Treatment Volume-70 (PTV- 70) treatment volumes received the treatment dose of at least 63 and 70 Gy, respectively. The conventional-boost technique was used for 3D-CRT and the simultaneous integrated boost technique was used for other techniques. RESULTS The doses obtained from carotid arteries, thyroid and submandibular glands using IMRT, IMAT, and FIT were significantly lower than 3D-CRT. The study results pointed out the possibility of giving a treatment dose of 70 Gy to the PTV of EGI. with all planning techniques, with some advantages and disadvantages between them. All IMRT techniques provided superiority to 3D-CRT on the doses of the carotid artery, the thyroid gland, the submandibular glands, and the pharyngeal constrictor muscles with less variation between them. CONCLUSION The IMAT and 3D-CRT techniques yielded lower monitor unit values compared to other techniques. Normal tissue radiation exposure was lowest with the 3D-CRT technique. We recommend to increase the treatment dose from 63 Gy to 70 Gy in the radiotherapy of EGL cancer but to select the technique according to the patient's condition.

e22014 Background: Children with primaries in the head and neck region, especially those who recieve radiotherapy (RT) are at increased risk for second malignancies (SM). This study aims to assess the incidence and outcome of SM in children with head and neck primary tumors. Methods: During 1990-2017, 3214 children with cancer were treated in theIstanbul University, Oncology Institute. The primary tumor was in the head and neck region in 1414 (651 brain tumors,289 retinoblastoma,474 other). Survivors followed up for at least 3 years from diagnosis were evaluated for second malignancies. Results: 30 SM were identified in 28 survivors (18 male,10 female) at a median of 12 years (2-26) from diagnosis. The primary diagnosis was nasopharyngeal carcinoma (NPC) in 8, bilateral retinoblastoma (RBS) in 7, embryonal brain tumors (CNST) in 8, Hodgkin lymphoma (HD) in 3, rhabdomyosarcoma(RMS) in 2. Two RBS patients who did not recieve radiotherapy developed pilocytic astrocytoma (at 2 years) and osteosarcoma of the extremity (at 4 years) each, both are alive with no evidence of disease (NED) for 3.5 and 10 years. 26 patients recieved RT: one with CNST developed MDS (at 8 years) and died due to complications after stem cell transplantation (SCT). One with NPC developed PNET of the bladder (at 5 years) and died of disease (DOD). One with relapse HD developed Langerhans cell histiocytosis 2 years after SCTand is with NED for 10 years. The other 23 developed SM in the/proximity of the RT field. These SM were 7 sarcomas (in 4 retinoblastoma,2 NPC, 1 RMS), 6 thyroid cancer (in 2 CNST, 1 RMS, 1 HD, 1 NPC), 3 meningiomas (in 2 CNST, 1 RBS), 5 carcinomas (in 4 NPC, 1 RBS), 1 basal cell carcinoma (in a recurrent re-irradiated CNST, is with NED), 1 peripheral nerve sheath tumor (in 1 HD, DOD), glioblastoma multiforme and non Hodgkin's lymphoma (in the same CNST case, DOD at 6 months). One of the NPC case developed both sarcoma (at 18 years) and carcinoma (at 25 years, NED). The RT dose (20-70 Gy) differed according to diagnosis. All survivors of thyroid cancer are with NED except one who died in an accident; of 3 meningiomas, the one with retinoblastoma who developed malignant meningioma died. Of five carciinomas as SM, two with NPC who developed carcinomas died. Of sarcomas as SM, two with fibrosarcomas are with NED at 10 years each (1NPC, 1 RMS). All patients survived for a median of 3 (0.5-16) years after SM; 16/28 (57%) are with NED at a median of 8 (1-16) years; 12 died at a median of 1.8 (0.5-4.75) years after SM. (1 CNST due to accident, 1 NPC due to infectious complications after a reconstructive surgery, 10 DOD). All SM were detected early during regular surveillance. Conclusions: Children with head and neck primaries are at risk for SM which may occur many years later, especially in RT sites. RT should be avoided when possible such as currently in RBS. Patients need regular surveillance lifelong, for early detection of SM. SM should be treated with curative intent, to achieve long term survival.

We designed our study to analyze the prognostic factors and treatment outcomes of adult medulloblastoma patients who received postoperative craniospinal irradiation. Fourty-three patients who were treated due to medulloblastoma at Istanbul University, Institute of Oncology between 1990 and 2013 were retrospectively analyzed. All of the patients were older than 18 years, with a median age of 27 years (range, 18–51 years). In 40 (93%) patients, total resection of the tumor was achieved, and 3 (7%) patients had undergone a subtotal tumoral resection. Risk assessment revealed 7 high-risk and 36 standard-risk patients. All patients received postoperative craniospinal irradiation, delivering a median craniospinal dose of 36 Gy, with an additional boost to the posterior fossa up to 54 Gy. Fifteen patients received chemotherapy. The median follow-up was 62 months (range, 3–213 months). The 5-year, 10-year, overall, and disease-free survival rates were 63%, 51%, 66%, and 55%, respectively. Univariate analysis revealed that hydrocephalus, initial local recurrence, subtotal resection in primary surgery, initial Karnofsky performance status ≤70, duration of symptoms shorter than 30 days, and primary site dose < 54 Gy were found to be negative prognostic factors. Toxicity was moderate. The main therapy in adult medulloblatoms is craniospinal irradiation following surgery. The prognostic factors and outcomes of the patients in our study are concordant with previous reports in the literature.

The aim of the study was to investigate the effect of the Hybrid technique which was created by combining of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of nasopharyngeal cancer (NPC) patients. 7 to 9 field IMRT, triple arc VMAT, and Hybrid plans were generated for 10 advanced stage NPC patients. The homogeneity index (HI) and the conformity index (CI) of planning target volumes (PTVs) were calculated for each technique to evaluate the plan quality. The techniques were compared in terms of plan quality, sparing of organs at risk (OARs), monitor units (MUs), and delivery time. Hybrid technique significantly improved the target dose homogeneity and the conformity for PTV70 and PTV60 compared to IMRT and VMAT. Hybrid plans significantly reduced the maximum dose of the brainstem sparing compared to the VMAT plans and also improved the sparing of spinal cord compared to IMRT and VMAT. The MUs and the delivery time of Hybrid plans were found to be between values for IMRT and VMAT plans. Hybrid technique can be useful when IMRT and VMAT techniques are not adequate alone in the treatment of NPC patients.

Objective Radiotherapy is the primary method of treatment for nasopharyngeal cancer (NPC) and many side effects were reported in patients receiving radiation to this area. This study was conducted to evaluate the long-term effects of radiotherapy following NPC on olfactory bulb (OB) volume and olfactory function. Methods Twenty-four patients with NPC who received radiotherapy at least 12 months ago were recruited. Fourteen healthy subjects with similar demographical characteristics were recruited as the healthy control group. All volunteers were subjected to a nasoendoscopical examination, and abnormalities that could potentially cause olfactory dysfunction were the exclusion criteria from the study. An experienced radiologist segmented the MRI coronal, axial and sagittal slices manually for three-dimensional OB volume measurement in a blinded manner. Olfactory function was assessed using the Connecticut Chemosensory Clinical Research Center (CCCRC) test, and average score (0: worst, 7: best) was calculated as the total CCCRC olfactory score. Results The mean CCCRC score was 5.5 ± 1.1 for the nasopharyngeal cancer patients, whereas the mean score of healthy control group was 6.4 ± 0.4. There was a significant difference in the olfactory scores (p = 0.003). The mean OB volume in the NPC group was 46.7 ± 12.1 mm3. Among the patients with NPC, the cisplatin receiving group had a mean OB volume of 47.2 mm3, whereas the cisplatin + docetaxel receiving group had a mean OB volume of 46.5 mm3, and they were similar. The MRI measurement of the healthy control group was 58.6 ± 13.8 mm3. The OB volumes of the healthy control group were significantly higher (p Conclusion Radiotherapy following nasopharyngeal cancer results in a diminished OB volume and deteriorated olfactory function. Chemosensory olfactory dysfunction might be a contributing factor to lack of appetite, cancer cachexia and consequent lowered quality of life in NPC patients.

Background: Carcinoma of the tongue is the most common intra-oral malignancy in Western countries. Incidence and mortality rates have increased in recent years, and survival has not improved. This study aimed to determine etiologic factors for tongue cancer with age-sex matched case-control data. Materials and Methods: 47 patients with carcinoma of the tongue referred to our oral medicine clinic between years 2005-2006 were analyzed and compared with control group data. The medical records , including family history of cancer, dental trauma, and history of abuse of alcohol and tobacco products was recorded for all subjects. Chi square comparison tests and linear regression analysis were performed using the SPSS program for statistics. Results: Patient and randomly selected control groups each consisted of 30 male and 17 female subjects with mean ages 53.2 (±12.6) and 52.6 (±11.5) years respectively. Smoking and alcohol abuse proportions were significantly higher in the patient group (p=0.0001, p

Background Current treatment of locoregionally advanced NPC (LRA-NPC) is CCRT with or without adjuvant chemotherapy (CT). The value of adding IC to CCRT in LRA-NPC is unclear. We retrospectively evaluated LRA-NPC patients treated with IC followed by CCRT in a single tertiary center in Turkey. Methods Between 2004 and 2016, 202 patients with nonmetastatic LRA-NPC (stage 3-4), 144 males and 58 females ranging from 17 to 75 (median 49) years old, were treated with IC followed by CCRT. Eleven (%5.4) patients had keratinised (WHO I), and 191 (%94.6) had nonkeratinised or undiffrentiated (WHO II-III) carcinoma. Cumulative radiation dose to primary tumor ranged from 60 to 74 (median 70) Gy. Ninety-one (%45) of the patients received 2-dimensional and 111 (%55) received intensity modulated radiotherapy (IMRT). IC consisted of taxane (T)(75 mg/ m2) and platinum (P)(75 mg/m2) combination (199 patients) or P and fluorouracil or epirubicine (3 patients) combination and 188 of the patients received 3 cycles of IC. Concomittant P was used either weekly (40 mg/m2, 25 patients) or every 3-weekly (100 mg/m2, 177 patients) application. Follow-up ranged from 5 to 167 months (median, 72.5 months). Table: 1143P . Patient and treatment characteristics n ( % ) Stage III IVA IVB 149 (73.7%) 30 (14.9%) 23 (11.4%) Number of induction courses 2 3 4 10 (5%) 188 (93.1%) 4 (2%) Concomittant type Every 3 weeks (100 mg/m2) Every week (40 mg/m2) 177 (87.6%) 25 (12.4%) RT technique 2-dimensional Intensity modulated 91 (45%) 111 (55%) Radiation dose to primary (Gy) ≤ 70 > 70 8 (4%) 194 (96%) Results Treatment failure was observed in 52 (%25.7) of the patients (21 local, 13 regional and 27 distant). Distant failure rate of all the patients exceeds 13%. Five and 10 years disease free survival (DFS) rates are 75.2% and 70.4% and overall survival (OS) rates are 78.9% and 64% respectively. In univariate analysis patient age favoring those below 49 and stage of disease favoring WHO II-III were all significant predictors of DFS and OS. In addition pathology was a significant predictor of DFS. Conclusions LRA-NPC patients treated with IC followed by CCRT have a high locoregional control (LRC) rate. Despite the use of IC distant control remains insufficient and continues to be a challenge in NPC. Besides improving LRC, more effective systemic therapy is needed. Legal entity responsible for the study Musa Altun, MD. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

e17507 Background: Standard treatment of locoregionally advanced nasopharyngeal carcinoma (LRA-NPC) is CCRT with or without adjuvant chemotherapy (CT). The value of adding IC to CCRT in LRA-NPC is unclear. We aimed to retrospectively evaluate LRA-NPC patients treated with IC followed by CCRT and analyse patient, tumor, treatment characteristics and outcome. Methods: Between 2004 and 2016, 202 patients with nonmetastatic LRA-NPC (stage 3-4), 144 males and 58 females ranging from 17 to 75 (median 49) years old were treated with IC followed by CCRT. Eleven (%5.4) patients had keratinised (WHO I), and 191 (%94.6) had nonkeratinised or undiffrentiated (WHO II-III) carcinoma. Cumulative radiation dose to primary tumor ranged from 60 to 74 (median 70) Gy. Ninety-one (%45) of the patients received 2-dimensional and 111 (%55) received intensity modulated radiotherapy (IMRT). IC consisted of taxane (T)(75 mg/ m2) and platinum (P)(75 mg/m2) combination (199 patients) or P and fluoruracil or epirubicine (3 patients) combination and 188 of the patients received 3 cycles of IC. Concomittant P was used either weekly (40 mg/m2, 25 patients) or every 3-weekly (100 mg/m2, 177 patients) application. Follow-up ranged from 5 to 167 months (median, 72.5 months). Results: Treatment failure was observed in 52 (%25.7) of the patients (21 local, 13 regional and 27 distant failures). Distant failure rate of all the patients exceeds 13%. Five and 10 years disease free survival (DFS) rates are 75.2% and 70.4% and overall survival (OS) rates are 78.9% and 64% respectively. In univariate analysis patient age favoring those below 49 and stage of disease favoring WHO II-III were all significant predictors of DFS and OS. In addition pathology was a significant predictor of DFS. Conclusions: LRA-NPC patients treated with IC followed by CCRT have a high locoregional control rate. Despite the use of systemic (induction) chemotherapy distant control remains insufficient and continues to be a challenge in NPC treatment. Besides improving locoregional control more effective systemic therapy is needed. [Table: see text]

Radiotherapy (RT) with concomitant chemotherapy (CT) has improved the therapeutic outcome of patients with locally advanced nasopharyngeal carcinoma (LANC). However, the importance of induction CT before definitive therapy is still undefined. Patients (n=59) who had LANC were included in this retrospective study. They received induction CT consisting of cisplatin and docetaxel followed by definitive RT with cisplatin. The median age was 49 years (18-68). All patients were of stages II (15%), III (63%) and IV (22%). Fifty eight patients could receive 3 cycles of CT. Except one patient, there was no grade 3 or 4 toxicity during induction CT. Chemoradiotherapy could be given to 49 patients (83%). Twelve percent of patients had complete response after induction CT and this number had increased to 95% after the completion of the therapy. Objective responses (complete and partial) were 100% after the completion of the therapy. Median follow up time was 29 months. Nine patients had relapse (2 had local only, 4 distant, 3 local and distant). Three patients who had both local and distant relapse died during follow-up. Three year overall and progression free survival rates were 94.9% and 84.7%, respectively. Induction CT with docetaxel and cisplatin is a feasible and tolerable treatment for patients with LANC.

Purpose In radiotherapy planning of heterogeneous regions, differences which negatively affect the quality of the plan in terms of homogeneity and conformity may occur between the optimal dose volume histogram (DVH) and the final calculated DVH. The intermediate dose calculation (IDC) module, which is included in the Analytical Anisotropic Algorithm (AAA), is used even though the planning period is slightly increased in radiotherapy plans of lung tumors with low tissue density to reduce these differences. The purpose of this study is to examine the impact of IDC on radiotherapy planning for the heterogeneous maxillary sinus region. Methods In this study, the homogeneity index (HI) and the conformity index (CI) of the intensity modulated radiotherapy plans prepared using Eclipse-TPS and AAA v8.9 of 12 patients with maxillary sinus cancer were calculated. The original plans were re-optimized with the same optimization criteria by using AAA v15.1 with and without IDC. HI and CI values of the new plans were calculated after re-optimization. The HI and CI values, maximum doses and the critical organ doses were compared between the original and new plans. Results AAA v15.1 with IDC increased the plan quality in terms of HI, CI and maximum dose values. The HI values (ideal value=0) were found to be 0.093, 0.090 and 0.067; the CI values (ideal value=1) were found to be 1.149, 1.142 and 1.055; the maximum doses were found to be 108.1%, 107.8% and 105.3% for AAA v8.9, AAA v15.1 without IDC and AAA v15.1 with IDC, respectively. The differences between AAA v15.1 with IDC and the others are statistically significant for HI values, CI values and maximum doses but there is no significant difference for the doses received by critical organs. Conclusions The use of the IDC increases the quality of intensity modulated radiotherapy plans in heterogeneous regions such as head and neck. This work was supported by Scientific Research Projects Coordination Unit of Istanbul University (Project Number: I.U.BAP-23057)

10547Background: The aim of this study is to evaluate the demographic, clinical and therapeutic characteristics and long-term outcome in childhood nasopharyngeal carcinoma (NPC) in a single center....

Long non-coding RNAs (lncRNAs) have been shown to be aberrantly expressed in head and neck cancer (HNC). The aim of the present study was to evaluate plasma levels of three lncRNA molecules (lincRNA-p21, GAS5, and HOTAIR) in the treatment response in HNC patients treated with radical chemoradiotherapy (CRT). Forty-one patients with HNC were enrolled in the study. Most of the patients had nasopharyngeal carcinoma (n = 27, 65.9 %) and locally advanced disease. Blood was drawn at baseline and treatment evaluation 4.5 months after therapy. lncRNAs in plasma were measured by semiquantitative PCR. Treatment response was evaluated according to clinical examination, RECIST and PERCIST criteria based on magnetic resonance imaging (MRI), and positron emission tomography with computed tomography (PET/CT) findings. Complete response (CR) rates were 73.2, 36.6, and 50 % for clinical investigation, PET/CT-, or MRI-based response evaluation, respectively. Predictive value of lncRNAs was investigated in patients with CR vs. those with partial response (PR)/progressive disease (PD). We found that post-treatment GAS5 levels in patients with PR/PD were significantly higher compared with patients with CR based on clinical investigation (p = 0.01). Receiver operator characteristic (ROC) analysis showed that at a cutoff value of 0.3 of GAS5, sensitivity and specificity for clinical tumor response were 82 and 77 %, respectively. Interestingly, pretreatment GAS5 levels were significantly increased in patients with PR/PD compared to those with CR upon MRI-based response evaluation (p = 0.042). In contrast to GAS5, pretreatment or post-treatment lincRNA-p21 and HOTAIR levels were not informative for treatment response. Our results suggest that circulating GAS5 could be a biomarker in predicting treatment response in HNC patients.

Aim: Undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive tumour; a randomized study evaluating neoadjuvant chemotherapy with bleomycin/epidoxorubicin/cisplatin (BEC) in addition to conventional radiotherapy has resulted in a better disease-free survival in the chemotherapy arm. The bleomycin infusion in the BEC regimen has necessitated hospitalization for the infusion, and resulted in serious pulmonary toxicity. This study has aimed to omit the bleomycin, and test the efficacy and toxicity of cisplatin (C) and a higher dose of epidoxorubicin (EPI) in patients with locally advanced UNPC. Methods: Seventy-one patients with locally advanced UNPC were treated with three cycles of C 100mg/m 2 day 1, and EPI 100mg/m 2 day 1 every 3 weeks followed by conventional radiotherapy of 70Gy. Results: Neoadjuvant chemotherapy was well tolerated. There was only 1-week delay in 14.3% of the patients and no dose modification. Grade III–IV neutropenia occurred in 18.9% of the cycles; none of the patients developed neutropenic fever. No patient progressed during chemotherapy, the complete response rate was 26.8% (95% CI=16.9–38.6) and the partial response rate was 59.1% (95% CI=46.8–70.7) for an objective response rate of 85.9% (95% CI=75.6–93.0) at the end of the three cycles of chemotherapy. After the completion of radiotherapy, the complete response rate increased to 81.7% (95% CI=70.7–89.9) and the objective response increased to 91.5% (95% CI=82.5–96.8). The median disease-free interval and the median survival have not been reached. The 5-year disease-free and overall survival rates are 53.0% (95% CI=43.7–62.0) and 57.2% (95% CI=48.3–65.2), respectively. Conclusion: Neoadjuvant C and EPI, easily administered in the outpatient setting, is an effective and well-tolerated regimen in the treatment of locally advanced UNPC. Onat, H. et al . (2002). Clinical Oncology 14 , 449–454 Copyright 2002 The Royal College of Radiologists. Published by Elsevier Science Ltd. All rights reserved.

e17544 Background: To evaluate pre and post-treatment Epstein-Barr virus (EBV) DNA copy numbers, to investigate changes with treatment and the possibility of using it as a follow-up marker in nasopharyngeal carcinoma (NPC) patients. Methods: Blood samples were obtained before (0-3 weeks) and after treatment (mean 6 weeks) and number of EBV DNA copies were determined by PCR . Treatment was administered as concomittant chemoradiotherapy ± induction chemotherapy. MRI and PET-CT were performed prior (0-4 weeks) and after (6-16 weeks) treatment. Mann Whitney test was used for 2 group comparisons of parameters with no normal distribution and comparison of quantitative data. Fisher-Freeman-Halton and Wilcoxon Signed Ranks tests were used for comparison of qualitative data and intra-group comparison of parameters with non-normal distribution. Kaplan Meier Survival analysis was used to assess survival. Results: The study included 50 NPC patients treated between 2011 and 2015. Median follow-up is 25.3 (27.5 ± 14) months. 12 patients had residual-recurrent or metastatic (3 patients initially had distant metastasis) disease. Mean survival is 49.77 ± 2.4 months. Median posttreatment EBV DNA level is lower than pretreatment EBV DNA level (p = 0.001). Pretreatment EBV DNA copy numbers are higher in patients with residual-recurrent or metastatic disease (RRM) than those without RRM (p=0.05). Mortal patients had higher pre (p = 0.015) and post (p = 0.043) treatment EBV DNA levels than those who survived. Overall survival (OS) is higher in patients with undetectable (n:41) than those with detectable (n:9) EBV DNA levels after treatment (p = 0.02). Conclusions: The OS is lower in patients with higher pretreatment and detectable posttreatment EBV DNA levels. This study implies that pre and post treatment serum EBV DNA levels can be used as prognostic indicators and also be beneficial as a follow up marker in NPC patients. [Table: see text]

M30 and M65 are circulating fragments of cytokeratin 18 released during apoptotic cell death and regarded as markers of cell death in patients with various tumor types. Our aim was to investigate the clinical and prognostic significance of the serum M30 and M65 concentrations in patients with advanced nasopharyngeal carcinoma. Thirty-two patients with nasopharyngeal cancer and 32 control subjects were investigated. Serum samples were obtained on first admission before any treatment was initiated. Serum M30 and M65 concentrations were measured by quantitative enzyme-linked immunosorbent assay. Median serum M30 (181.5 vs. 45.5 U/L, p

e21012 Background: The aim of this study was to evaluate the demographic, clinical and therapeutic characteristics and long-term outcome in childhood and adolescent nasopharyngeal carcinoma (NPC) r...

To date there are no prognostic factors that can account for the biology and disease behavior in nasopharyngeal cancer. Therefore, identification of new factors that can help in predicting the behavior of the disease and characterizing the subgroup with more aggressive tumors more likely to benefit from chemotherapy is important. In this study, c-erb B2, bcl-2, and mutant p53 protein levels were investigated in sera and tumor tissue of patients with nasopharyngeal cancer. Serum c-erb B2 levels were significantly higher in the patients than in the healthy subjects. No meaningful difference was observed between the serum and tissue levels of the mutant p53 protein. Tissue bcl-2 concentrations were considerably high. Our results suggest that serum c-erb B2 levels may aid in identifying a subgroup of patients with a poorer response rate to first-line treatment.

Purpose: We present our experience with computed tomography (CT) for delineating the extent of bone erosion in nasopharyngeal carcinoma (NPC) and propose that a new subdivision of Stage T4 disease be added to the staging criteria for cases of minimal bone disease, defined as erosion of the base of the sphenoid or the pterygoid without cranial nerve (CN) involvement. Methods and Materials: We retrospectively reviewed the clinical findings, radiological findings, and treatment outcome in 64 patients with Stage T4 NPC, diagnosed according to the American Joint Committee on Cancer 4th edition criteria. The median follow-up was 34 months (range, 3–118 months). Statistical analyses were performed using the chi-square test, the Kaplan-Meier method, and the log-rank test. Results: Local control was achieved in 19 (46%) of 41 patients with CN deficits and 18 (78%) of 23 patients without CN deficits ( p = 0.01). Overall 5-year survival with and without CN deficits was 25% and 58%, respectively ( p = 0.01). When the 16 patients with minimal bone disease were compared to the remaining 48 patients, there were significant differences in local control rates (87% vs. 48%, p = 0.006) and 5-year survival rates (68% vs. 28%, p = 0.008). Conclusion: Among patients with Stage T4 NPC, a subgroup of patients with only minimal bone disease may have a more favorable prognosis, which may have a considerable bearing on our approach to this patient group.

Nasopharyngeal carcinoma (NPC) is a rare and distinct malignancy that arises from the epithelium of the nasopharynx. It accounts almost 1 % of all pediatric malignancies. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. Here we present 3 male NPC patients 13, 14 and 15 years old. One of them had stage III and the others stage IV diseases. Administered dose of radiation was 66 Gy for case I, 70 Gy for case II and 68 Gy for case III. The follow-up period was more than 12 months except for case III and all of them were disease free in their last visit. All attended dental clinics for dental and TMJ problems. Dentitions were severely affected, trismus and severe xerostomia. Long term effects of radiotherapy which has a great impact on patients’ quality of life and the role of supportive care and minimizing the late effects of ionizing radiation are discussed.

Purpose: To report a retrospective analysis of epidemiologic, clinical, and therapeutic aspects of 50 children with newly diagnosed nasopharyngeal carcinoma who were treated in a single institution over a period of 18 years. Methods and Materials: Thirty-two male and 18 female children ranging from 5 to 16 years, accounted for 7.2% of all nasopharyngeal carcinoma cases and 52% of childhood nasopharyngeal malignancies. Histopathology was World Health Organization Type 3 carcinoma in 45, World Health Organization Type 2 in 4, and World Health Organization Type 1 in one patient. Two of the patients had missing information for staging and treatment evaluation. Disease extent was T1 ( n = 4), T2 ( n = 9), T3 ( n = 21), and T4 ( n = 14); N0 ( n = 1), N1 ( n = 6), N2 ( n = 12), and N3( n = 29). Six patients had base of skull invasion, two had cranial nerve palsies, and six had both. One patient had M1 disease on admission. Twenty-three patients were treated with irradiation only. Thirteen patients received adjuvant, and 12 had neoadjuvant chemotherapy in addition to radiotherapy. Patients received 50–72 Gy to the primary tumor and involved nodes, and 45–50 Gy to uninvolved regions. Chemotherapy consisted of combinations including cisplatin, bleomycin, epirubicin, 5-flouroucil, and cyclophosphamide. Results: Thirty-eight (79%) patients attained locoregionel control. Overall, 22 patients are alive without relapse 6–195 months from diagnosis. Thirteen patients had 21 relapses, at local and/or regional sites (43%), distant sites (48%), or both (9%). The median time for first relapse was 8 months. Overall, the 5-and 10-year survival rates were 52 and 52%, respectively, and the failure-free survival rates were both 53%. The results of three distinct treatments given in subsequent time periods were not statistically different. Three second malignancies occurred 33–156 months following nasopharyngeal carcinoma diagnosis. Conclusion: In the current series, nasopharyngeal carcinoma patients under the age of 16 accounted for 7.2% of all nasopharyngeal carcinoma cases. Whereas the impact of chemotherapy on long-term survival remains to be determined by randomized studies, the results suggest that more effective treatment regimens and long-term follow-up are necessary for children with nasopharyngeal carcinoma.

Summary Background Thirty adult patients with head and neck soft tissue sarcoma (HNSTS) treated between 1987 and 2000 were retrospectively analysed. Patients and methods The most frequent histopathological subtypes were chondrosarcomas (27%) and malignant fibrous histiocytoma (20%). The surgical resection was performed in 25 of the 30 patients (83%). Twenty-three patients in the surgical resection arm received postoperative radiotherapy. Results Five-year local control rates for patients with negative surgical margins (n = 9), microscopically positive disease (n = 10), gross residual disease (n = 6) and inoperable cases (n = 5) were 64, 70, 20 and 0%, respectively. However, there was no significant difference in local control between patients with negative or microscopically positive disease who received postoperative radiotherapy (71 vs. 70%). The patients who received doses ≥60 Gy had significantly higher local control rates than the ones who received doses lower than 60 Gy (p = 0.048). The local control rates were lower in patients with grade 2–3 tumours when compared with grade 1 tumours (44 vs. 83%). The median overall survival of whole group was 31 months. Median survivals of patients receiving both surgery and radiotherapy with negative and microscopically positive margins were significantly better than patients who were not treated with surgery (34.8 and 36 vs. 13.3 months). Conclusion Our results confirm that the optimal treatment of HNSTSs is complete surgical excision, and that postoperative adjuvant radiotherapy clearly improves local control.

Nasopharyngeal carcinoma (NPC) is a characteristic tumor displaying epidemiological, genetic and regional distribution properties and is unique by its natural behavior and therapy. Investigation of the molecular and biological changes, gene amplifications and activations that occur during carcinogenesis and progression can provide new insight into the pathology of the disease and may add biological factors that can be used as new prognostic markers. The p53 tumor suppressor gene is the most frequently mutated gene in human cancer. Although point mutations in the p53 gene are observed in nasopharyngeal cancer, the mutation rate is lower than in other tumors. Immunohistochemical studies have shown significant p53 overexpression in NPC material. In this study, p53 protein immunoreactivity was investigated in paraffin sections of primary nasopharyngeal tumors and metastatic cervical lymph nodes and association with clinical and histopathological characteristics was evaluated. Ninety-seven paraffin sections from 81 patients with NPC treated from 1990 to 1996 were examined by immunohistochemistry and were correlated with clinical features and treatment outcome. Among a total of 97 samples, positive staining for p53 protein was observed in 83 (85.5%) samples while no staining was found in 14 (14.5%) cases. Immunoreactivity was observed in 62 (81.5%) of the primary nasopharyngeal biopsy specimens. The correlation between p53 expression and histological type, stage, age and sex distributions was tested. After statistical analysis according to Chi-square test and Yates' correction, no significant difference was demonstrated (p0.05). There was no statistically significant correlation with p53 immunoreactivity and overall and disease-free survival. Although the association between NPC and p53 is not clear, our study confirms that p53 overexpression is present in a considerable subset of patients with NPC.

The taxanes are the most active new agents for squamous-cell carcinoma of the head and neck (SCCHN) since the discovery of cisplatin. Our aim was to define the therapeutic efficacy and toxicity of paclitaxel and cisplatin combination therapy in patients with recurrent SCCHN. Patients with locally recurrent or metastatic SCCHN were enrolled in the study. Patients were required to be chemotherapy-naive, and should have completed radiation therapy at least 6 weeks prior to enrollment. A World Health Organization (WHO) performance status of less than 3 was required. Paclitaxel (Taxol, Bristol Myers Squibb Company, Princeton, NJ) and cisplatin therapy (PC) consisted of prophylaxis with pheniramine 50 mg i.v., ranitidine 150 mg i.v. and dexamethasone 20 mg i.v. given prior to paclitaxel 175 mg/m2 as a 3-hour i.v. infusion, followed by cisplatin 75 mg/m2 as a 1-hour infusion with an additional 3000 cc of saline for hydration. This treatment was repeated every 3 weeks for a maximum of six cycles. Patients were evaluated for response after the third and sixth cycles, or at the time of clinical progression. Fifty patients were enrolled in the study. The overall response rate was 32% with a 10% complete response rate. Forty-eight patients were assessable for toxicity. A total of 221 cycles of chemotherapy was given and the most common toxicity was myelosuppression; 7.7% of cycles had grade III-IV neutropenia. Severe neuropathy, nephropathy, mucositis, and emesis were uncommon (

6087 Background: Due to improvements in treatment, the importance of new primaries in nasopharyngeal carcinoma (NPC) patients is increasing. The aim of this study is to evaluate new primaries in NP...

Amplification of the c-erbB-2 gene has been associated with poor prognosis in different types of cancer. However, there are no data on the c-erbB-2 expression levels in nasopharyngeal cancer. In this study, amplification of the gene has been investigated in the tumor tissue of patients with nasopharyngeal cancer by competitive polymerase chain reaction c-erbB-2 amplification was observed in 43.3% of the patients. The increase in the gene copy number correlated with the T stage. No correlation was found with lymph node involvement, histologic grade, differentiation, presence of metastases, or age and sex. We conclude that c-erbB-2 amplification may contribute to the pathogenesis of nasopharyngeal cancer. Our report is the first study investigating the expression of the c-erbB-2 gene in nasopharyngeal cancer at the DNA level.

Undifferentiated carcinoma of the nasopharynx (UCNT) is a particular head and neck epidermoid lineage tumor related to the Epstein Barr Virus (EBV). It has geographically selective endemic epidemiologic features, without relation to external carcinogens. Its systemic agressiveness is the source of most disease-related demises, because radiotherapy achieves excellent local control and a significant percentage of cure in patients with exclusive locoregional disease. Differences in the staging systems currently in use, the recent changes in imaging and radiotherapy technology, and the lack of distinction between UCNT and squamous cell carcinoma (SCC) of the nasopharynx in Western literature reports make for some difficulty in therapeutic results evaluation when analyzing available literature. Its chemosensitivity is a relatively recent acknowledged fact, and its use in metastatic patients results in a high percentage of objective responses, many of long duration. Neoadjuvant cisplatin-based chemotherapy seems to be of benefit, but outstanding controversies in this regard will be soon answered through ongoing phase III trials. After a review of the current literature of all the above-mentioned aspects of this fascinating nosologic entity, our own experience, both in metastatic and locoregional disease patients is analyzed.

e16017 Background: Radiation treatment with concomitant chemotherapy has improved the therapeutic outcome of patients with locally advanced nasopharyngeal carcinoma. However, the importance of neoa...

20507 Background: To evaluate the role of surgery and radiotherapy in the treatment of soft tissue sarcomas of the head and neck region Methods: Thirty adult patients with head and neck soft tissue sarcoma were retrospectively analyzed. The most frequent histopathologic subtypes were chondrosarcomas (27%) and malignant fibrous histiocytoma (20%). The surgical resection was performed in 25 of the 30 patients (83%). Negative surgical margins could be achieved only in 9 of 25 patients (36%). Ten patients had marginal resection (40%) and 6 patients (24%) had gross residual disease after the surgery. All patients in the surgical resection arm received postoperative radiotherapy except two patients. Results: Five-year local control rates for patients with negative surgical margins (n=9), microscopically positives (n=10), gross residual disease (n=6) and inoperable (n=5) cases were 64%, 70%, 20% and 0% respectively. The median disease free survivals were 26.6 months, 17.7 months, 8.4 and 5.5 months. However, there was no significant difference in local control between patients with negative or microscopically positive disease who receive postoperative radiotherapy (71% vs 70%). The higher dose of radiotherapy (= 60Gy) was found to be associated with a longer local control (p=0.048). The local control rates were lower in patients with grade 2–3 tumors as compared with grade 1 tumors (44% vs. 83%). The median overall survival of whole group was 31 months. Median survivals of patients receiving both surgery and radiotherapy with negative and microscopically positive margins were significantly better than patients who were not treated with surgery (34.8 and 36 months vs. 13.3 months). In univariate analysis grade 1–2 vs. 3, had statistically significant 5-year survival difference (64% vs. 14%, p=0.003). The presence of local relapse had clear negative effect on survival (absent vs. present 66% vs. 7%, p=0.0003). Conclusions: Our results and the findings in the literature confirm that the optimal treatment of head and neck soft tissue sarcomas is complete surgical excision. Postoperative adjuvant radiotherapy clearly improves local control however the high locoregional failure rates still indicate the need for improved treatment strategies. No significant financial relationships to disclose.

Purpose: To assess the value of hemoglobin concentration (HC) in predicting treatment outcomes in nasopharyngeal carcinoma (NPC) patients treated with chemotherapy (CT) and radiotherapy (RT). Patients and Methods: Ninety-eight NPC patients treated with three courses of platinum-based neoadjuvant CT (NCT) and conventional RT were grouped as having normal HC (greater than or equal to12.0 g/dl in females and greater than or equal to13 g/dl in males), having mild anemia (MA) (13.0 g/dl>Hbgreater than or equal to11 g/dl in males, 12.0 g/dl>Hbgreater than or equal to11 g/dl in females) and having severe anemia (SA) (Hb