Musa Altun

Undifferentiated nasopharyngeal cancer (UCNT): Current diagnostic and therapeutic aspects

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. Difference in the staying 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.

Nasopharyngeal carcinoma in children: Retrospective review of 50 patients

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-fluoroucil, and cyclophosphamide. RESULTS Thirty-eight (79%) patients attained locoregional 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.

The role of surgery and radiotherapy in treatment of soft tissue sarcomas of the head and neck region: Review of 30 cases

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>or=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.

c-erbB-2 Gene Amplification in Nasopharyngeal Carcinoma

Abstract 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.

Induction chemotherapy with docetaxel and cisplatin is highly effective for locally advanced nasopharyngeal carcinoma

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.

Locally advanced nasopharyngeal carcinoma: computed tomography findings, clinical evaluation, and treatment outcome∗

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.

Carcinoma of the Tongue: A Case-control Study on Etiologic Factors and Dental Trauma

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<0.0001 respectively). Chronic mechanical trauma was observed in 44.7% of the patients and 17.0% of the control group (p=0.004). Similarly, family history of cancer of any type (for the first degree relatives) was found to be more common in the patient group (p=0.009). On regression analysis, alcohol abuse, family history of cancer, smoking, chronic mechanical traumas appeared as significant etiologic factors (p=0.0001). CONCLUSIONS We believe that field cancerization may become evident in oral and oropharyngeal mucosa with multiple steps of molecular changes starting from the first sign of dysplasia with chronic exposure to etiological factors. Chronic trauma cases need particular attention to search for very early signs of cancer.

Olfactory bulb volume and olfactory function after radiotherapy in patients with nasopharyngeal cancer

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 ± 12.1mm(3). Among the patients with NPC, the cisplatin receiving group had a mean OB volume of 47.2mm(3), whereas the cisplatin+docetaxel receiving group had a mean OB volume of 46.5mm(3), and they were similar. The MRI measurement of the healthy control group was 58.6 ± 13.8mm(3). The OB volumes of the healthy control group were significantly higher (p<0.05). 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.

Serum and tissue c-erb B2, bcl-2, and mutant p53 oncoprotein levels in nasopharyngeal cancer.

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.

Human Papillomavirus in Head and Neck Cancer

Throughout the last three decades, there has been a notable shift in the epidemiology of head and neck cancer (HNC) worldwide. A rapidly spreading subtype of HNCs is caused by human papillomavirus (HPV) infection. HPV-related cancers are now considered to constitute 30–65% of all HNC cases and 50–80% of oropharyngeal cancers. HPVpositive oropharyngeal cancers have a unique demographic profile and tumor biology characteristics. HPV-associated patients predominantly consist of younger men with better performance status and fewer comorbid diseases. They have better dentition, higher numbers of oral sex partners, and use less amount of tobacco or alcohol, higher amount of marijuana compared with HPV-negative patients. In addition, patients with HPVpositive tumors have a 60–80% reduced mortality rates, a finding that was confirmed by multiple trials and led to several ongoing deintensification studies. This chapter describes epidemiologic features of HPV-positive HNC, risk factors for HPV infection and HPVassociated oropharyngeal cancer, HPV detection methods, mechanisms of carcinogene‐ sis and improved treatment response, and the impact of HPV status on clinical outcome as well as deintensification approaches and potential of vaccination.