Lack of effect of daily N-acetylcysteine supplementation on mutagen sensitivity

The European Organization for Research and Treatment of Cancer multicenter Euroscan trial was set up to prevent the occurrence of second primary tumors in the upper aerodigestive and respiratory tract in patients cured for early stage head and neck squamous cell carcinoma. One randomized group of patients receive daily N-acetylcysteine, an antioxidant that may be protective especially in the early steps of carcinogenesis. Mutagen sensitivity, measured as sensitivity to bleomycin in peripheral blood lymphocytes, has been found to be increased in head and neck squamous cell carcinoma and is hypothesized to reflect cancer susceptibility. The aim of this study was to investigate whether mutagen sensitivity is influenced by oral N-acetylcysteine supplementation and can therefore be used as intermediate end point in chemoprevention. Patients (n = 19) who had various periods of N-acetylcysteine supplementation (600 mg daily for 3-9 months) were analyzed. In addition, a patient group (n = 14) that did not receive N- acetylcysteine supplementation was analyzed for comparison. Our results show no evidence that administration of N-acetylcysteine did influence the mutagen sensitivity level. The only explanatory variable in the analysis of the difference between two samples of one person was the b/c value of the first measurement. Moreover, the variability in these repeated measurements (coefficient of variation of 14%) indicates that additional studies should be performed to minimize this variability and to optimize the testing of mutagen sensitivity to accurately identify individual patients at high risk fur the development of multiple primary tumors

Facial nerve function in carcinoma of the parotid gland

Aim: To analyse, for patients with carcinoma of the parotid gland, the prognostic value for treatment outcome of the function of the facial nerve (NVII), and determining facial nerve dysfunction after treatment. Methods and materials: In a retrospective study of the Dutch head and Neck cooperative group (NWHHT), data of 324 patients with parotid carcinoma were analysed. The function of N VII before treatment was intact in 77%, partially and completely impaired in 14% and 7%, respectively Eighty-eight percent of the patients were treated surgically, and 77% of them were treated by a combination of postoperative radiotherapy In 21% NVII was sacrificed, a reconstruction was performed in one of three. Results: Independent risk factors for N VII dysfunction before treatment were tumour localisation, positive neck nodes at presentation, pain, increasing age, and perineural invasion. Regional, not local, control was significantly impaired for complete facial paralysis. N VII dysfunction was an independent factor for disease free survival, and was 69%, 37% and 13% for normal, partially and completely impaired function, respectively. After treatment 22% of the patients experienced a partial paralysis, and 13% of the patients experienced a complete parlysis of N VII. Conclusion: For patients with parotid carcinoma, facial nerve function before treatment is a strong prognostic factor for disease free survival. (c) 2006 Elsevier Ltd. All rights reserved

External validation of the prognostic index for patients with parotid carcinoma

We previously performed a Cox proportional hazards regression analysis and constructed a prognostic model, based on a “source population” of 151 parotid carcinoma patients from the Netherlands Cancer Institute. The resulting information was used to create a prognostic index (Vander Poorten VLM, Balm AJM, Hilgers FJM, Tan IB, Loftus-Coll BM, Keus RB, et al. The development of a prognostic score for patients with parotid carcinoma. Cancer 1999;85:2057-67). Table 1 displays PS1, a pre-treatment index, and PS2, incorporating data from the surgical specimen. For one patient, such an index sums the weighted contributions of each important clinical and histological characteristic into one number, corresponding to the outcome, tumor recurrence. In this way for instance, a patient of 74 years old with a 3 cm painful suspect nodule in the left parotid gland, without sings of facial nerve weakness, skin invasion or palpable neck nodes, can be told before treatment to have a 59% chance of being tumor free 5 years following standard treatment, if the lesion proves to be malignant.status: publishe

The role of radiotherapy in the treatment of malignant salivary gland tumors

We analyzed the role of primary and postoperative low linear energy transfer radiotherapy in 538 patients treated for salivary gland cancer in centers of the Dutch Head and Neck Oncology Cooperative Group, in search for prognostic factors and dose response. The tumor was located in the parotid gland in 59%, submandibular gland in 14%, oral cavity in 23%, and elsewhere in 5%. In 386 of 498 patients surgery was combined with radiotherapy, with a median dose of 62 Gy. Median delay between surgery and radiotherapy was 6 weeks. In the postoperative radiotherapy group, adverse prognostic factors prevailed. Elective radiotherapy to the neck was given in 40%, with a median dose of 50 Gy. Primary radiotherapy (n = 40) was given for unresectable disease or M(1), with a dose range of 28-74 Gy. Postoperative radiotherapy improved 10-year local control significantly compared with surgery alone in T(3-4) tumors (84% vs. 18%), in patients with close (95% vs. 55%) and incomplete resection (82% vs. 44%), in bone invasion (86% vs. 54%), and perineural invasion (88% vs. 60%). Local control was not correlated with interval between surgery and radiotherapy. No dose-response relationship was shown. Postoperative radiotherapy significantly improved regional control in the pN(+) neck (86% vs. 62% for surgery alone). A rating scale for different sites, T stage, and histologic type may be applied to calculate the risk of disease in the neck at presentation, and so indicate the need for elective neck treatment. A marginal dose-response was seen, in favor of a dose > or =46 Gy. A clear dose-response relationship was shown for patients treated with primary radiotherapy. Five-year local control was 50% with a dose of 66-70 Gy. Postoperative radiotherapy with a dose of at least 60 Gy is indicated for patients with T(3-4) tumors, incomplete or close resection, bone invasion, perineural invasion, and pN(+). In unresectable tumors, a dose of at least 66 Gy is advisabl

Prognostic index for patients with parotid carcinoma - External validation using the nationwide 1985-1994 Dutch Head and Neck Oncology Cooperative Group database

BACKGROUND. Validation of the prognostic indices for the recurrence-free interval of patients with parotid carcinoma, the development of which was described in a previous report, is needed to be confident of their generalizability and justified prospective use. METHODS. The Dutch Cooperative Group on Head and Neck Cancer database contains 231 patients with parotid carcinoma from six tertiary referral centers who were seen between 1985-1994. This database was used to validate the predictive value of the prognostic indices, PSI (pretreatment index predicting recurrence) and PS2 (posttreatment index predicting recurrence), in patients with parotid carcinoma. Validation methods included calculation of both indices for each patient, comparison of coefficients, construction of survival curves using the published cutoff points, and calculation of concordance measure C. Wald tests for optimization of scale and weights of the contributing variables, and for possible score improvement by including other variables, were also performed. RESULTS. The 5-year disease-free rate was 62% (standard error = 4%). PSI was calculated for 183 patients. The previously set cutoff points resulted in 5-year disease-free rates that ranged from 92% (PSI = 1) to 42% for the least favorable group (PSI = 4). Concordance measure C was 0.74. The postoperative score, PS2, was calculated for 171 patients. Previous cutoff points resulted in 5-year disease-free rates that ranged from 90% (PS2 = 1) to 40% (PS2 = 4). Concordance measure C was 0.71. Both PSI and PS2 did not improve using the findings in this independent material. CONCLUSIONS. The prognostic indices performed adequately in this validation sample. This finding demonstrates that the prognosis of a parotid carcinoma patient can be quantified by using a weighted combination of the parameters of age, pain, clinical T (cT) classification, clinical N (cN) classification, skin invasion, facial nerve dysfunction, perineural growth, and involved surgical margins. A quantified prognosis, in terms of the recurrence-free interval, can be used to provide information to the patient, to perform clinical trials, and eventually to make clinical decisions. A user-friendly translation and computerized calculation of the indices should be the next step toward generalized prospective use and repetitive evaluation of the indices. (C) 2003 American Cancer Societ