ABSTRACT
Purpose: High Dose Rate (HDR) remote afterloading brachytherapy machine and advanced treatment planning system have made it possible to make variations in individual dwell times across a catheter according to tumour density and for sparing normal structures. New inverse planning technique such as Inverse Planning Simulated Annealing (IPSA) has also been introduced. But very few institutions are venturing towards volume based IPSA optimised intracavitary brachytherapy. This study focuses on dwell time deviation constraint (DTDC) feature of IPSA based optimization which restricts the large variation of dwell time across the catheter. Methods and Material: For this retrospective study we have generated IPSA optimised intracavitary brachytherapy plans for 20 cancer cervix applications. The initial DTDC value of each IPSA plan was kept 0.0. Later on gradual increment was made in DTDC values in step of 0.2. Plan modulation index (M) defined by Ryan L. Smith et al was used for characterising the variation of dwell time modulation with respect to gradual increase in DTDC parameter. Results: Plan modulation index gradually decreases with increasing value of DTDC from 0.0 to 1.0. There was the 83% decrease in M value from IPSA of DTDC 0.0 to fully constrained IPSA of DTDC1.0. There is reduction of 8.26% and 6.95% for D2cc values of rectum and bladder respectively for DTDC 1.0 compared to DTDC 0.0. Conclusions: One of the benefits of applying DTDC constrained in IPSA plan is that, it removes local hot spots. It's another advantage is the reduction in rectum and bladder dose.
ABSTRACT
PURPOSE: There is no study till date determining the spectrum of adverse events of pazopanib in Indian patients with advanced sarcoma. MATERIALS AND METHODS: We conducted a retrospective study by analyzing the case records of metastatic sarcoma patients treated with pazopanib from January 2016 to July 2017 in sarcoma medical oncology clinic. Toxicity was assessed according to CTCAE v.4.03 criteria. SPSS version 23 was used for statistical evaluation. RESULTS: A total of 33 patients received pazopanib. The median age was 41 years (range, 19–75 years), with a male predominance (54.5%). Twenty-six patients (78.8%) had ECOG performance status 1 at the time of pazopanib initiation. The most common type of sarcoma was synovial sarcoma, and the mean duration of pazopanib intake in patients was 4.12 months. The median follow-up was 13 months. Median progression-free survival was 5 months, and median overall survival was 18 months. Overall response rate was 6.0%. Out of the 33 patients, 42.4% (n = 14) received it after first line of therapy. Six patients (18.2%) required dose reductions due to toxicity. Thirteen (39.4%) patients experienced CTCAE grade 3 or 4 toxicities. Most common grade 3 and 4 toxicities experienced among patients were hand–foot skin reaction (18.2%) and proteinuria (9.1%). No significant difference was seen when analyzed for variables such as age, sex, ECOG performance status, comorbidities, and number of previous lines received in patients experiencing grade 3 and 4 toxicities. CONCLUSIONS: The spectrum of adverse events in Indian patients at doses lower than the recommended dose is distinctly different from the western population. However, this unique toxicity profile needs to be validated in prospective studies.
ABSTRACT
Stroke is the third leading cause of death and disability around the globe. The aim of the present investigation was to evaluate the protective effect of hesperidin and its nitric oxide mechanism against cerebral ischemia reperfusion injury. Bilateral common carotid artery occlusion for 30 min followed by 24 h reperfusion was given to induce ischemia in rats. Animals were pretreated with hesperidin (50 and 100 mg/kg, po) for 7 days. Various behavioural tests, oxidative stress parameters, endogenous antioxidant system, antioxidant enzyme activity and mitochondrial enzyme complex (I, II, III and IV) dysfunctions in cortex and striatum were assessed subsequently. Hesperidin (50 and 100 mg/kg) significantly improved neurobehavioral alterations (neurological score, locomotor activity, resistance to lateral push and hanging wire latency), attenuated oxidative damage, restored antioxidant and mitochondrial complex enzyme activities in cortex and in striatum regions of the brain as compared to their respective controls. L-arginine (100 mg/kg) or L-NAME (10 mg/kg) pretreatment with lower dose of hesperidin (50 mg/kg) significantly reversed or potentiated its protective effect, respectively which was significant as compared to hesperidin (50 mg/kg). The results highlight the involvement of nitric oxide mechanism in the protective effect of hesperidin against ischemia reperfusion injury induced alterations.