Development and validation of a nomogram for prediction of survival and local control in laryngeal carcinoma patients treated with radiotherapy alone: a cohort study based on 994 patients.

INTRODUCTION: To advise laryngeal carcinoma patients on the most appropriate form of treatment, a tool to predict survival and local control is needed. MATERIALS AND METHODS: We performed a population-based cohort study on 994 laryngeal carcinoma patients, treated with RT from 1977 until 2008. Two nomograms were developed and validated. Performance of the models is expressed as the Area Under the Curve (AUC). RESULTS: Unfavorable prognostic factors for overall survival were low hemoglobin level, male sex, high T-status, nodal involvement, older age, lower EQD(2T) (total radiation dose corrected for fraction dose and overall treatment time), and non-glottic tumor. All factors except tumor location were prognostic for local control. The AUCs were 0.73 for overall survival and 0.67 for local control. External validation of the survival model yielded AUCs of 0.68, 0.74, 0.76 and 0.71 for the Leuven (n=109), the VU Amsterdam (n=178), the Manchester (n=403) and the NKI cohort (n=205), respectively, while the validation procedure for the local control model resulted in AUCs of 0.70, 0.71, 0.72 and 0.62. The resulting nomograms were made available on the website www.predictcancer.org. CONCLUSIONS: For patients with a laryngeal carcinoma treated with RT alone, we have developed visual, easy-to-use nomograms for the prediction of overall survival and primary local control. These models have been successfully validated in four external centers.

Intensity-modulated radiation therapy for oropharyngeal cancer: radiation dosage constraint at the anterior mandible.

Because the survival of endosseous implants in irradiated bone is lower than in non-irradiated bone, particularly if the irradiation dose exceeds 50Gy, a study was carried out to assess the irradiation dose in the anterior mandible, when intensity modulated radiation therapy (IMRT) is used. The hypothesis was that adequate IMRT planning in oropharyngeal cancer patients is allowing sufficiently low anterior mandibular bone radiation dosages to safely insert endosseous implants. Ten randomly selected patients with oropharyngeal cancer, primarily treated by intensity-modulated radiotherapy (IMRT), were included in this study. First, at five determined positions distributed over the anterior mandible, the appropriate radiation dosages were calculated according to the originally arranged fractionated radiation schedule. Second, for each patient an adjusted fractionated radiation schedule was established with an extra dose constraint which allowed a lower dose in the mandible taking into account that the anterior mandible needs protection against radiation-induced osteoradionecrosis. The goal for the adjusted fractionated radiation schedule was similar as that of the original fractionated radiation schedule, including a desired tumour target dosage of 70Gy and maximum mean local dosages for organs at risk. The data revealed a considerable and statistically significant, irradiation dose reduction in the anterior mandible without compromising the other constraints. As a result of this study it is strongly advised to maximize dose constraint to the anterior mandible when planning irradiation for oropharyngeal cancer patients, using IMRT. This would greatly facilitate successful implant treatment for this group of patients. The fractionated radiation schedules used, should also be used for the planning of the best implant positions by integrating them in the implant planning software.

Predictive value of lymph node metastases and extracapsular extension for the risk of distant metastases in laryngeal carcinoma.

OBJECTIVE: The objective of this retrospective chart analysis was to determine the prognostic value of the lymph node status and extracapsular lymph node extension (ECE) of the neck for the development of distant metastases in squamous cell carcinoma of the larynx. METHODS: One hundred sixty-five patients treated for laryngeal carcinoma with a neck dissection with histologic evaluation were included. Primary study end point was distant metastasis-free survival. Univariate analysis with the Kaplan-Meier method was used to calculate distant metastasis-free survival and overall survival for the whole group and for groups according to ECE/lymph node status. Patients were classified as 1) no metastatic lymph nodes, 2) metastatic lymph nodes without ECE, or 3) metastatic lymph nodes with ECE. Univariate Cox regression was performed with outcome distant metastasis-free survival. RESULTS: The median overall survival for the whole group was 5.1 years and the 5-year survival rate was 51%. The median distant metastasis-free survival for the whole group could not be calculated and the 5-year metastasis-free survival rate was 78%. The hazard ratio was 3.4 (95% confidence interval [CI] = 1.0-12.1) for patients with positive nodes and without ECE and 10.5 (95% CI = 3.6-30.8) for the patients with metastatic nodes and with ECE compared with the patients without metastatic lymph nodes. CONCLUSION: The presence of ECE in metastatic lymph nodes augments the risk of distant metastasis by nine times in laryngeal carcinoma. Metastatic lymph nodes without ECE show a risk three times greater.

A 15-year-old girl with a spindle cell carcinoma of the parotid gland. A diagnostic challenge solved by immunohistochemistry and cytogenetic analysis.

Spindle cell carcinoma is a rare neoplasm of the upper respiratory tract which occurs in adults, most commonly in the larynx. In the literature only one case of spindle cell carcinoma, located in the maxilla, has been reported in a child. We report the first presentation of a spindle cell carcinoma in a child, which was located in the parotid gland, together with the clinical course. The diagnostic challenge associated with this unusual disorder is elucidated, as well as the role of immunohistochemical and cytogenetic examination to define the nature of these lesions.

Quality of life after curative radiotherapy in Stage I non-small-cell lung cancer.

PURPOSE: The aim of this study was to investigate changes in quality of life (QOL) among medically inoperable Stage I non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy. PATIENTS AND METHODS: The study sample was composed of 46 patients irradiated for Stage I NSCLC. Quality of life was assessed before, during, and after radiotherapy using the European Organization for the Research and Treatment of Cancer QLQ-C30 and QLQ-LC13. Changes in symptom and QOL scores over time were evaluated with a repeated measurement analysis of variance using the mixed effect modeling procedure, SAS Proc Mixed. Twenty-seven patients were treated only at the primary site, whereas for 19 patients, the regional lymph nodes were included in the target volume as well. RESULTS: The median follow-up time of patients alive was 34 months. The median survival was 19.0 months. None of the locally treated patients developed regional recurrence. A significant, gradual increase over time was observed for dyspnea, fatigue, and appetite loss. A significant, gradual deterioration was observed also for role functioning. No significant changes were noted for the other symptoms or the functioning scales. Significantly higher levels of dysphagia, which persisted up to 12 months, were observed in those in which the regional lymph nodes were treated, as compared to the locally treated patients. Radiation-induced pulmonary changes assessed with chest radiograph were more pronounced in the group treated with locoregional radiotherapy. CONCLUSIONS: After curative radiotherapy for Stage I medically inoperable NSCLC, a gradual increase in dyspnea, fatigue, and appetite loss, together with a significant deterioration of role functioning, was observed, possibly because of pre-existing, slowly progressive chronic obstructive pulmonary disease and radiation-induced pulmonary changes. Taking into account the low incidence of regional recurrences after local irradiation, the higher incidence and severity of radiation-induced changes, and the higher levels of dysphagia persisting up to 12 months, local irradiation of the primary tumor without elective irradiation of the regional lymph nodes may be the most appropriate treatment for patients with small, peripherally located tumors.