Importance of pedigree in patients with familial epilepsy and intellectual disability.

In this study, we prospectively evaluated demographic characteristics, clinical findings and pedigree patterns in 70 patients with familial epilepsy and/or intellectual disability (ID)/global developmental delay (GDD) and/or motor retardation but without specific etiologic diagnosis to determine genetic inheritance patterns by using at least a three-generation pedigree analysis. Mean age of the patients was 6.85 ± 3.93 years and male/female ratio was 1.50. There was consanguinity between the parents of 47 (67.1%) patients. Only epilepsy was diagnosed in 14 patients; only ID/GDD in 22; epilepsy and ID/GDD in 9 and epilepsy and ID/GDD and motor retardation in 25 patients. Genetic inheritance pattern was definitely determined in 60 (85.7%) patients, and most of the patients (61.4%) displayed autosomal recessive inheritance. Based on our findings, we suggest that a three-generation pedigree analysis should be obtained in all patients with familial neurological disorders, including epilepsy, ID/GDD and motor retardation, to optimise counselling, screening and diagnostic testing.

Outcomes of patients with tonsillar carcinoma treated with post-tonsillectomy radiation therapy.

BACKGROUND: Our aim was to evaluate the therapeutic outcomes of patients with squamous cell carcinoma of the tonsil that underwent tonsillectomies followed by radiotherapy. METHODS: A search of the database maintained within the Department of Radiation Oncology at The University of Texas M. D. Anderson Cancer Center identified 120 patients with carcinoma of the tonsil who were irradiated between 1979 and 2004 following total gross removal of their disease by tonsillectomy. RESULTS: Thirty-six patients had stage III disease and 64 patients had stage IV disease. Only 12 patients received systemic chemotherapy. With median follow-up of 51 months, the 5-year local-regional control rate, recurrence-free survival rate, and overall survival rates were 97%, 92%, and 86%, respectively. CONCLUSION: Patients who undergo tonsillectomies resulting in total gross removal of their primary disease followed by radiation have excellent outcomes. Our common practice is to deliver 66 Gy to the tonsillar bed. This practice has resulted in extremely high local control rates.

Concurrent epithelioid malignant peripheral nerve sheath tumor and papillary thyroid carcinoma in the treated field of Hodgkin's disease.

BACKGROUND: Simultaneous malignancies in the field of radiation for Hodgkin's disease is an extremely rare event. A unique case of concurrent thyroid and neck mass in the postirradiation field of a young patient with Hodgkin's disease is presented. METHODS AND RESULTS: Thyroidectomy and excision biopsy of the neck mass were performed. A 1.5-cm papillary thyroid carcinoma was identified in thyroidectomy and an initial diagnosis of undifferentiated malignant neoplasm was rendered on the neck mass biopsy. Subsequent surgical excision of the neck mass and immunohistochemical analysis revealed malignant peripheral nerve sheath tumor. CONCLUSION: Concurrent malignancies in the field of treatment of Hodgkin's disease may occur. Rare malignancies including malignant peripheral nerve sheath tumor may be encountered along with the more common papillary thyroid carcinoma.

Combination of radiotherapy with EGFR antagonists for head and neck carcinoma.

The introduction of biologically sound radiation fractionation regimens and combinations of radiotherapy with chemotherapy have gradually improved both the survival of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and the prospect of organ preservation. Long-term follow-up, however, has shown that some of the radiation-chemotherapy combinations are associated with increased late toxicity. This observation, in conjunction with advances in tumor biology, has led to the launch of investigations into molecular markers and targets for therapeutic interventions. Research on the epidermal growth factor receptor (EGFR)-mediated signaling pathway has enriched our understanding of the biology of HNSCC, in terms of carcinogenesis and cellular processes governing tumor response to therapy. The finding that the addition of an antibody-based inhibitor of the EGFR pathway to radiotherapy significantly improves locoregional control and overall survival rates in patients with locally advanced HNSCC, without increasing radiation-induced toxicity, has resulted in the growing acceptance of such combined regimens as a frontline therapy option for locally advanced HNSCC. Because such therapy has benefited only an additional 10%-15% of patients, studies are being undertaken to identify markers and mechanisms of resistance to EGFR antagonists that are essential for the further refinement of therapy. Overall, preclinical and clinical studies on EGFR have validated the concept that selective tumor radiation sensitization can be achieved by modulating a specific perturbed signaling pathway, and these studies have increased the enthusiasm for developing and investigating other novel agents targeting other cellular processes.