Comparative Study of Dysphagia-optimized Intensity Modulated Radiotherapy (Do-IMRT) and Standard Intensity Modulated Radiotherapy (S-IMRT) and Its Clinical Correlation in Head and Neck Cancer Patients.

OBJECTIVE: Dosimetric sparing of critical swallowing structures like constrictor muscles and larynx can lead to improved functional outcomes in head and neck cancer patients treated by chemoradiation. METHODS: A total of 50 Patients with newly diagnosed, biopsy proven AJCC stage II-IV head and neck squamous cell cancers (HNSCC) were prospectively studied. 25 patients were randomized in each arm of Dysphagia-optimized Intensity Modulated Radiotherapy (Do-IMRT) arm and Standard Intensity Modulated Radiotherapy (SIMRT) arm. Additional dose constraints were applied to the dysphagia/aspiration at risk structures (DARS) in Do-IMRT arm. The impact of using Do-IMRT was assessed by the difference in mean scores of MD Anderson Dysphagia Inventory (MDADI), University of Washington-Quality of Life (UW-QOL), and 100 ml Water Swallow Test (WST). RESULTS: Patients in both arms showed significant (P <0.01 or P < 0.001) improvement in MDADI (global and composite), UW-QOL and Water Swallow Test scores. However, the improvements were found significantly higher in Do-IMRT as compared to S-IMRT. Significant improvements i.e. mean change from baseline to 12 months (P <0.05 or P <0.01 or P <0.001) were 19. 2, 8.6, 14.3, 7.4, 18.6 and 22.0%  higher respectively in Do-IMRT as compared to S-IMRT  in MDADI global and composite scores, UW-QOL swallowing scores, and 100 ml Water Swallow  (swallowing volume, swallowing capacity and swallowing speed)  test scores. CONCLUSION: The Do-IMRT improves swallowing functions compared to S-IMRT in HNSCC patients treated with radical chemoradiation.

Leptin DNA Methylation and Its Association with Metabolic Risk Factors in a Northwest Indian Obese Population.

BACKGROUND: It is well established that obesity is a major health risk in diabetes and associated diseases. Epigenetic changes, specially DNA methylation, play an important role in regulation of adipokines. The objective of the present study was to evaluate the DNA methylation status at the promoter region of the leptin gene in obese individuals and its association with metabolic risk factors. METHODS: The study included obese (n=100) and non-obese (n=75) individuals aged 25-45 years, and measured their physical, biochemical parameters (glucose, insulin, and lipid profiles) and leptin, DNA methyltransferase 1 (DNMT1), and DNA methyltransferase 3 beta (DNMT3b) mRNA expressions with real-time reverse transcription-polymerase chain reaction (qRT-PCR). DNA methylation of the leptin gene at the promoter region was analyzed by methyl-specific qPCR . RESULTS: The study found that the DNA methylation level at the promoter area of the leptin gene was negatively associated with weight in obese subjects. Furthermore, study findings showed that the DNA methylation level was negatively associated with fasting insulin, glucose, homeostatic model assessment for insulin resistance, and total cholesterol. There was also a higher expression of DNMT1 and DNMT-3b in obese subjects as compared with non-obese subjects. CONCLUSION: The leptin epigenetic profile may be associated with obesity and its associated metabolic risk factors.

Understanding molecular markers in recurrent oral squamous cell carcinoma treated with chemoradiation.

INTRODUCTION: Oral cancer accounts for approximately 2.1% of all cancers worldwide. In India, oral squamous cell carcinoma (OSCC) is the most common cancer with half a million new cases diagnosed every year. More than 50% of patients eventually develop local recurrence or metastasis usually within the first 2-years following completion of treatment. It is beneficial to analyze the prognostic significance of Cyclin D1, p53 and EGFR which are critical mediators in the pathogenesis of OSCC. The objective of this study was to assess the association of expression of these markers with recurrence and pattern of recurrence in OSCC patients undergoing chemoradiation. MATERIALS AND METHODS: A Total 290 OSCC cases of locally advanced stage (III, IV) oral cancer with World Health Organization (W.H.O.) performance status of grade 0/1 in the year 2009-2012 were enrolled in the study. Treatment response was assessed according to W.H.O. criteria. Cyclin D1, EGFR and p53 expression in tumor tissue was estimated by immunohistochemical (IHC) method and quantified as percentage positive nuclei. RESULTS: During the 2-years follow up, 56 (19.3%) patients recurred, out of which, 47 (83.9%) were locoregional and 9 (16.1%) distant sites. On correlating, χ2 test showed significant (P < 0.05 or P < 0.01 or P < 0.001) association of marker expressions (Cyclin D1, EGFR and p53) with recurrence. The strong positive expressions of all three markers showed significant association with early time of recurrence. The multivariate logistic regression analysis showed significant (P < 0.05 or P < 0.01 or P < 0.001) association of recurrence with primary site, differentiation, Cyclin D1 and p53 expressions indicating these as an independent predictors of recurrence in OSCC. The Cyclin D1, EGFR and p53 expressions also showed significant (P < 0.001) poor survivals (OS, DFS and RFS) in patients with positive/strong positive expressions than negative expression suggesting their prognosis in OSCC. CONCLUSION: Our results signifies that tumors over expressing Cyclin D1, EGFR and p53 are resistant to chemoradiation and are associated with increased risk of locoregional recurrence and metastasis in OSCC patients undergoing chemoradiation.