Survival outcomes and failure patterns for oropharyngeal cancers treated with simultaneous integrated boost in intensity modulated radiotherapy (SIB-IMRT) and concurrent chemotherapy.

BACKGROUND: Intensity modulated radiotherapy (IMRT) has become a standard radiotherapy treatment delivery option owing to the advantages it offers in terms of target coverage and organ sparing. Furthermore, the ability to introduce different fractionation for different targets lets us deliver higher doses to the high-risk areas and lower doses to the elective volumes at the same sitting, referred to as simultaneous integrated boost (SIB). In the current study, we intended to retrospectively analyze the clinical outcomes and patterns of the failure of oropharyngeal cancers treated with SIB-IMRT and concurrent chemotherapy at our centre and analyze the factors contributing to poorer outcomes. MATERIAL AND METHODS: Data of oropharyngeal cancer patients treated with SIB-IMRT and concurrent chemotherapy were retrieved from the institutional database. Patient demographic details, histopathological features, staging, treatment details, failure patterns and outcomes were documented. All potential factors were evaluated for outcomes. Radiation was delivered by using the SIB-IMRT technique. High-risk planning target volume (PTV) received 66 Gy in 2.2 Gy/fraction, intermediate and low-risk PTV received 60 Gy and 54 Gy, respectively. Primary endpoint was to assess local control (LC), regional control (RC) and loco-regional control (LRC) rates and secondary end point was to evaluate the survival outcomes - overall survival (OS) and cancer-specific mortality. All survival analyzes were performed using the Kaplan-Meier method. RESULTS: A total of 169 cases were included in the final analysis. The median age was 55 years (range 20-78) with 95.3% males. The base of tongue was the most common primary site. Around 54% cases were node negative with 38% patients having stage IV disease. The local control rates for N0 vs. N+ cases were 74.1 vs. 62.3% (P = 0.046), respectively. Similarly, the 4-year RC rates for N0 vs. N+ cases were 94.4 vs. 83.5% (P = 0.024), respectively. On multivariate analysis, only 4-year RC rates showed significant difference between the two (P = 0.039). No differences were found between T stages in LRC and OS. The 4-year LRC rates for stages 1, 2 vs. 3, 4 were non-significant (69.2 vs. 66.3%; P = 0.178). The 4-year OS rate was 81.3%. The 4-year LC and LRC rates were 67.8 and 89.5%, respectively. There were 54 local and 17 regional failures. The median time to failure was 13 months (range 3.6-82.9). CONCLUSION: SIB-IMRT provides comparable outcomes for oropharyngeal cancers. OS and loco-regional recurrences were significantly worse for nodal positive disease.

Analyzing the impact of close margins and extra-resection margins on failure rates in postoperative oral cavity cancers.

BACKGROUND: Postoperative oral cancers with close margins belong to medium- to high-risk category for local failure. During re-surgery for close margins, there is sufficient doubt as to whether the re-excised tissue is from the same region as the close margin. Therefore, we planned a retrospective review of these cases of close margins that were re-excised with extra-resection margins (ERMs). MATERIAL AND METHODS: Details of 2011 oral cavity patients resected at our hospital were retrieved. Cases with close margins were segregated and the status of ERMs was noted. The postoperative histopathological details, radiotherapy details, and failure patterns in all these cases were documented. The primary objective of the study was to assess the overall survival (OS) and disease-free survival (DFS) in cases with ERMs. The secondary objective was to assess the local and regional control rates and variation with the number and status of close and ERMs. OS, DFS, and local failure rates were defined from the date of registration. Statistical analysis was performed with the SPSS statistical software package. All survival analyses were performed using the Kaplan-Meier method. Log-rank test was used to test the statistical significance. A P-value of 0.05 was considered statistically significant. RESULTS: Sixty-four cases with a median age of 47 years (range: 29-76) were considered for the final analysis. The median follow-up was 40 months (range: 9.5-56.5). The 2-year OS and DFS rates were 91.5% and 88.5%, respectively. The crude local and regional failure rates were 10.9% and 3.1%, respectively. The 3-year locoregional control rate was 90.2%. The 2-year locoregional control rate for one close margin was significantly better as compared to more than one close margin (P = 0.049). No difference in survival and failure rates was found between the number of ERMs resected (one vs. two) and ≤ vs. > 3 mm close margin status. Two patients developed bone metastases. CONCLUSION: The survival rates and locoregional control rates did not differ much between the groups that had one or more ERMs. However, the locoregional control rates were better in cases with one close margin as compared to those with more than one close margin. A larger study with longer follow-up is needed to detect statistically significant differences in outcomes and identify the factors that portend poor prognosis in these cases with close margins and ERMs.

Effect of hyperglycemia on acetylcholinesterase and catecholamine levels in rat brain and heart.

The effect of hyperglycemia due to experimental diabetes induced in rats, causes a decrease in the activity of Acetylcholinesterase in brain regions and heart; changes in the heart being more significant than the brain. Insulin administration reversed this effect in both the hear and the brain. Significant increase in the levels of catecholamines were also found in the brain regions in diabetes, which was reversed by insulin. The decreased activity of acetylcholinesterase observed in diabetes may be due to an early impaired glucose oxidation and glucose transport as a result of lack of insulin, which causes specific alterations in neurotransmitter levels, thereby effecting blood brain barrier transport, thus causing brain dysfunction.

Effect of chronic administration of propranolol on acetylcholinesterase and 5-hydroxytryptamine levels in rat brain and heart.

The effect of chronic administration of propranolol on the rat brain and heart acetylcholinesterase was studied by administering propranolol (5mg/kg body weight) for 14 days. This treatment was found to substantially inhibit the enzyme activity. Levels of 5-hydroxytryptamine were measured in the brain and heart; in brain the levels of 5-hydroxytryptamine increased with propranolol administration, while in the heart there was no change. Effect of different concentrations of propranolol on acetylcholinesterase activity was also studied in vitro and a decreased activity of the enzyme was found in brain and heart homogenates. The significance of these results is discussed in terms of the therapeautic effects of the drug in the control of hypertension.