Angelos Nikolaou

Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation

BACKGROUND Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial. PATIENTS AND METHODS Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m(2), epirubicin 75 mg/m(2) and paclitaxel (Taxol) 175 mg/m(2) (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m(2) (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients). RESULTS Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT. CONCLUSION IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.

Concomitant Radiochemotherapy vs Radiotherapy Alone in Patients with Head and Neck Cancer

The primary objective of the present randomized phase III trial was to compare the 3-yr survival rate of patients treated with standard fractionated radiotherapy (RT) alone or with the same RT concomitantly with cisplatin (DDP) or carboplatin (Cb). From January 1995 until July 1999, 124 patients with histologically proven locally advanced non-nasopharyngeal head and neck cancer (HNC) were randomized to receive either RT monotherapy (70Gy, Group A) or the same RT concomitantly with DDP (100 mg/m2 on d 2, 22, 42, Group B) or Cb (7 AUC on d 2, 22, 42, Group C). There were no significant differences in complete response rates between patients treated with RT alone or combined chemoradiotherapy. However, median time to progression (TTP) and overall survival (OS) were significantly longer in patients treated with concomitant chemoradiotherapy. Thus, median TTP was 6.3, 45.2, and 17.7 mo in groups A, B, and C respectively (p=0.0002). Similarly, median OS was 12.2, 48.6, and 24.5 mo, respectively (p=0.0003). At 3 yr follow-up, 17.5% of patients in group A were alive compared to 52% in group B and 42% in group C (p<0.001). Patients treated with concomitant chemoradiotherapy experienced more frequently severe hematological toxicity. Also, severe nausea/vomiting was more pronounced in group B, as expected. The present study clearly demonstrated that concomitant chemoradiotherapy with platinum analogs significantly prolongs 3-yr survival and median OS in patients with locally advanced HNC compared to conventional RT alone.

Second Primary Neoplasms in Patients With Laryngeal Carcinoma

Objectives: To better define the characteristics of second primary malignancies appearing in patients suffering from head and neck cancers, and more specifically laryngeal carcinoma, and to elicit those parameters that may be of assistance in better diagnosing, treating, and predicting outcome in such patients.

PRIMARY LARYNGEAL LYMPHOMA: REPORT OF 3 CASES AND REVIEW OF THE LITERATURE

Extranodal lymphomas limited to the larynx are rare, accounting for less than 1% of all laryngeal neoplasms. The aim of this study was to report the experience of our department in the management of these aggressive lesions, as they require special diagnostic and therapeutic attention.

Factors influencing quality of life in laryngectomized patients

Abstract The aim of this study is to estimate the quality of life postlaryngectomy. A questionnaire was used. Fifty-six patients were enrolled answering 26 questions. The mean age was 60.2 (40–76) years and median post-treatment time 43 (7–120) months. The most frequent complaints of the patients were increased bronchial discharge (66%) and reduced olfactory function (63%). Communication problems with strangers was mentioned by 57% and with their family by 29%. With regard to the psychological status, 30% were ashamed of their voice, 32% were ashamed of their appearance, 42% stated that they were rather depressed, and 30% were feeling lonely. More than 3 out of 4 patients believed that their everyday life had been altered. Half of the patients experienced financial difficulties and 37% were not participating in social meetings outside their house. Statistical analysis was used in order to calculate the severity of each category of problems which the patient faced using the scale from 0 to 1. The average grade for functional disorders was 0.31, for communication problems 0.47, for psychological problems 0.29, for social problems 0.27, and for financial problems 0.51.

Wegener's granulomatosis presenting with bilateral facial nerve palsy.

Abstract Primary manifestation of Wegener’s granulomatosis in the mucosa of the middle ear is rather rare, and has been reported as presenting with serous otitis media, chronic otitis media, sensorineural hearing loss, and, in rare instances, unilateral facial palsy. Bilateral facial palsy has never been reported. This last fact constitutes the interest in our report of a 23-year-old female patient who presented with symptoms of recurrent bilateral otitis media, eventually developing sensorineural hearing loss and bilateral facial palsy. Soon thereafter neurological symptoms appeared and lung extension was noted. Histological examination of repeated biopsies taken from the nasal and middle ear mucosa was not conclusive for the suspected disease, and c-ANCA titers were also initially repeatedly negative. Eventually, positive lung biopsy and elevated c-ANCA titers when the patient had developed pulmonary granulomas confirmed the diagnosis of Wegener’s granulomatosis. Mastoid surgery with facial nerve decompression of the most severely afflicted side did not result in the recovery of facial nerve function. Medical therapy with corticosteroids and cyclophosphamide improved the clinical picture but were ineffective in improving the bilateral sensorineural hearing loss and the facial paralysis on the operated side. We would contribute to the literature a unique case of bilateral facial nerve palsy due to Wegener’s granulomatosis.

Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression and Survival in Operable Squamous-Cell Laryngeal Cancer

Introduction Prognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression. Patients and Methods We identified all patients with localized TNM stage I–III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS). Results Among 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504). Conclusion IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted.

Dermatofibrosarcoma protuberans with fibrosarcomatous transformation of the head and neck

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous neoplasm associated with a high cure rate. We present a case of aggressive DFSP with fibrosarcomatous areas in the head and neck. A 28-year-old Mediterranean female presented with a 45-day history of rapidly growing cutaneous lesion of the face. Surgical biopsy confirmed the diagnosis of DFSP. Subsequently, the patient underwent wide local surgical resection, followed by reconstruction. Histopathology report revealed fibrosarcomatous transformation and the patient underwent adjuvant radiotherapy. The patient continues to be disease free at the 35-month follow-up.Although DFSP behave as non-aggressive malignancy, surgery with complete removal of the affected area is the intervention of choice. Moreover, adjuvant treatment and follow-up of the patient is essential in order to prevent recurrence.

MMP9 but Not EGFR, MET, ERCC1, P16, and P-53 Is Associated with Response to Concomitant Radiotherapy, Cetuximab, and Weekly Cisplatin in Patients with Locally Advanced Head and Neck Cancer

Concomitant administration of radiotherapy with cisplatin or radiotherapy with cetuximab appear to be the treatment of choice for patients with locally advanced head and neck cancer. In the present retrospective analysis, we investigated the predictive role of several biomarkers in an unselected cohort of patients treated with concomitant radiotherapy, weekly cisplatin, and cetuximab (CCRT). We identified 37 patients treated with this approach, of which 13 (35%) achieved a complete response and 10 (27%) achieved a partial response. Severe side effects were mainly leucopenia, dysphagia, rash, and anemia. Tumor EGFR, MET, ERCC1, and p-53 protein and/or gene expression were not associated with treatment response. In contrast, high MMP9 mRNA expression was found to be significantly associated with objective response. In conclusion, CCRT is feasible and active. MMP9 was the only biomarker tested that appears to be of predictive value in cetuximab treated patients. However, this is a hypothesis generating study and the results should not be viewed as definitive evidence until they are validated in a larger cohort.

Primary pleomorphic adenoma of the external ear canal. Report of a case and literature review.

INTRODUCTION Primary neoplasms of the external ear canal are rare, and 5% of these tumors are of glandular origin. Ceruminal glands are modified sweat glands of the skin of the external auditory meatus that may give rise to (a) benign tumors such as ceruminous adenoma, pleomorphic adenoma, and syringocystadenoma papilliferum, and (b) malignant tumors such as ceruminous adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma. An alternative theory holds that pleomorphic adenomas may well arise from ectopic salivary tissue present in the external ear canal. These tumors are very rare and usually have a benign course. In this report, we describe an unusual case of pleomorphic adenoma of the external auditory canal associated with chronic infection of the middle ear. CASE REPORT A 60-year-old woman presented with exacerbation of left otalgia over a 6-month period. She had been affected with chronic otitis media and aural polyps for the last 13 years, for which she had received medical treatment only. A canal-filling aural polyp was noted on clinical examination. Subsequent biopsy and histologic examination revealed pleomorphic adenoma of the external ear canal, possibly with malignant elements. Magnetic resonance imaging showed no intracranial extension or any association with the adjacent parotid gland. The patient underwent modified radical mastoidectomy and complete resection of the tumor and the entire skin of the external auditory canal. Final histology and immunohistochemistry confirmed the absence of malignancy, and no recurrence has been reported 1 year postoperatively. CONCLUSIONS Pleomorphic adenoma is an extremely rare tumor arising from the ceruminal glands of the external ear canal. Nonspecific presentation and difficult histologic diagnosis characterize this benign neoplasm. Wide local excision is the mainstay of treatment.