Comparison of twice weekly palliative RT versus continuous hypofractionated palliative RT for painful bone metastases.

Background: Palliative hypofractionated radiotherapy (RT) is an effective mode of treating painful bone metastasis. While 8 Gy single fraction radiation is often effective for the same, for complicated bone metastases a protracted fractionated regimen is preferred, of which 30 Gy/10#/2weeks or 20 Gy/5#/1 week are the most common worldwide. However such schedules add to the burden of already overburdened radiation treatment facilities in a busy center, wherein alternative logistic favourable schedules with treatment on weekends are preferred. Here we compare the efficacy of a twice weekly schedule to that of standard continuous 20 Gy/5 #/1 week schedule in terms of pain relief, response and quality of life. Materials and methods: A prospective non randomized study was undertaken from Jan 2018 to May 2019, wherein eligible patients of complicated bone metastases received palliative radiotherapy of 20 Gy/5#, either continuously for 5 fractions from Monday to Saturday or twice weekly, Saturday and Wednesday, starting on a Saturday over about 2 weeks. Pain relief was assessed by the Visual Analogue Scale (VAS) and FACES pain scale recorded prior to starting palliative RT and at 4 weeks, 3 months and 6 months. Results: Thirteen patients received continuous Hypofractionated RT while 16 received it in a twice weekly schedule. Spine was the most common site receiving palliative Radiation (27/29), while breast cancer was the most common primary (16/29). The demographic and the baseline characteristics were comparable. The mean pain score decline at 4 weeks was 2.56 ± 1.1 and 2.71 ± 0.52 in the 5-day and the two-week schedule, respectively (p = 0.67). Conclusion: A twice weekly schedule over about two weeks was found to be equivalent in pain control and response to the standard fractionated palliative radiation and, thus, can be safely employed in resource constrained, busy radiotherapy centers.

Pattern of locoregional failure in postoperative cases of locally advanced carcinoma of buccal mucosa treated with unilateral versus bilateral neck radiation: lesson learned from a basic practice setup.

Background: Carcinoma of buccal mucosa forms a sizeable percentage of the diagnosed oral cavity cancers in India. There is limited data on elective treatment of the contralateral neck for well-lateralized carcinoma with no involved nodes in the contralateral neck. We conducted this study to compare locoregional control in patients treated with unilateral vs. bilateral neck irradiation. Materials and methods: 48 patients with carcinoma of buccal mucosa were selected. Patients were divided into unilateral and bilateral arms based on radiation treatment of the ipsilateral or bilateral neck. All patients received adjuvant radiation with Cobalt 60 unit. Patient-specific and follow-up data were collected from records and dosimetric data from treatment planning system (TPS). Chi-square and unpaired t-test was used to compare data between arms and Kaplan Meier plot; Cox regression was used for survival analysis. Results: After a median follow-up of 23 months, 15 (31.3%) patients had developed disease recurrence, 8 and 7 in the unilateral and bilateral arms, respectively (p = 0.591). There was no contralateral neck failure during the follow-up period. The 2-year disease-free survival was 68.2% and 72.2% in the unilateral and bilateral arms, respectively. Among risk factors for disease recurrence, depth of invasion (DOI), delay in starting radiation and planning target volume (PTV) coverage were significant contributing factors. Cox multivariate regression suggested DOI and delay in starting radiation to be significant prognostic factors for disease-free survival (DFS). Conclusion: Bilateral neck radiation does not provide any advantage over ipsilateral neck radiation for properly selected well lateralized buccal mucosal squamous cell carcinoma. Ipsilateral neck radiation facilitates better sparing of organs at risk.

Dosimetric and clinical outcomes of CT based HR-CTV delineation for HDR intracavitary brachytherapy in carcinoma cervix - a retrospective study.

BACKGROUND: Brachytherapy for carcinoma cervix has moved from Point A based planning to optimization of dose based on HR-CTV. Guidelines have been published by GEC ESTRO on HR-CTV delineation based on clinical gynecological examination and MR sequences. These have given significant clinical results in terms of local control. However, many centers around the country and worldwide still use CT based planning, which restricts HR-CTV delineation, as disease and cervix can rarely be differentiated on a planning CT. Various studies have been done to develop CT based contouring guidelines from the available data, but enough evidence is not available on the clinical outcome when treatment is optimized to HR-CTV contoured on CT images. The purpose of this study is to find out the relation between local control and dosimetry of HR-CTV as delineated on CT images. MATERIALS AND METHODS: Patients of locally advanced carcinoma cervix treated radically with EBRT of 50 Gy in 25# and at least 4 cycles of concurrent weekly Cisplatin having a complete or partial response to EBRT were taken for study. All patients had completed CT based Intracavitary brachytherapy to 21 Gy in 3# of 7 Gy per # with dose prescription at point A and optimizing dose to reduce bladder and rectal toxicity. Follow up data on locoregional recurrence was obtained. HR-CTV delineation was done retrospectively on the treatment plan following guidelines by Viswanathan et al. EQD2 doses for EBRT+BT were calculated for point A and HR-CTV D90. The dosimetric data to HR-CTV and to Point A were then compared with patients with locoregional control and with local recurrence. RESULTS: 48 patients were taken, all had squamous cell carcinoma. The median age was 48 years. 33.33% were stage IIA, the rest were stage IIB. Median follow-up was 30 months with 25% developing recurrence of the disease. HR-CTV D90 EQD2 dose was significantly higher in patients with locoregionally controlled disease than in patients with local recurrence (83.97 Gy10 vs. 77.96 Gy10, p = 0.002). Patients with HR-CTV D90 EQD2 dose greater than or equal to 79.75 Gy 10 had better locoregional control than patients receiving dose less than 79.75 Gy10 (p = 0.015). Kaplan Meier plot for PFS showed significantly improved PFS for patients receiving HR-CTV D90 dose of at least 79.75 Gy10 (log-rank p-value = 0.007). Three year progression free survival was 87.1% in patients receiving HR-CTV D90 dose of at least 79.75 Gy10. CONCLUSION: CT based HR-CTV volume delineation with the help of pre brachytherapy clinical diagrams and MRI imaging may be feasible in a select subgroup of patients with complete or near-complete response to external beam radiation.

Insights into the ameliorative effect of oleic acid in rejuvenating phenylhydrazine induced oxidative stress mediated morpho-functionally dismantled erythrocytes.

Phenylhydrazine (PHZ), an intermediate in the synthesis of fine chemicals is toxic for human health and environment. Despite of having severe detrimental effects on different physiological systems, exposure of erythrocytes to PHZ cause destruction of haemoglobin and membrane proteins leading to iron release and complete haemolysis of red blood cells (RBC). Involvement of oxidative stress behind such action triggers the urge for searching a potent antioxidant. The benefits of consuming olive oil is attributed to its 75% oleic acid (OA) content in average. Olive oil is the basic component of Mediterranean diet. Hence, OA has been chosen in our present in vitro study to explore its efficacy against PHZ (1 mM) induced alterations in erythrocytes. Four different concentrations of OA (0.01 nM, 0.02 nM, 0.04 nM and 0.06 nM) were primarily experimented with, among which 0.06 nM OA has shown to give maximal protection. This study demonstrates the capability of OA in preserving the morphology, intracellular antioxidant status and the activities of metabolic enzymes of RBCs that have been diminished by PHZ, through its antioxidant mechanisms. The results of the present study firmly establish OA as a promising antioxidant for conserving the health of erythrocyte from PHZ toxicity which indicate toward future possible use of OA either singly or in combination with other dietary components for protection of erythrocytes against PHZ induced toxic cellular changes.

Aqueous bark extract of Terminalia arjuna protects against cadmium-induced hepatic and cardiac injuries in male Wistar rats through antioxidative mechanisms.

Cadmium (Cd) is one of the most ubiquitous toxic heavy metal in the environment. The present study was conducted to evaluate the protective role of aqueous bark extract of Terminalia arjuna (TA) against Cd induced oxidative damage in hepatic and cardiac tissues as the TA bark extract has folkloric medicinal use in the treatment of various hepatic and cardiac disorders. Male Wistar rats were divided into 4 groups. The control group was treated with normal saline as the vehicle; the second group orally administered with TA (20 mg/kg bw) daily for 15 days; the third group injected with Cd-acetate (0.44 mg/kg bw, s.c.) every alternate day for a period of 15 days; and the fourth group was administered with TA, 60 min prior to Cd treatment. The biomarkers of organ damage were significantly increased in the Cd treated groups. Besides, a significant alteration in the tissue levels of biomarkers of oxidative stress, the activities and the levels of antioxidant enzymes was observed following treatment with Cd. Additionally, some of the enzymes were found to be inhibited uncompetitively by Cd when tested in an in vitro system. Furthermore, evidence gathered from studies on the histological parameters and mitochondrial membrane potential in both the tissues argue in favour of the possible protective role of TA against Cd induced damage. Finally, gas chromatography-mass spectrometry revealed the presence of eight major bioactive phytochemicals in aqueous bark extract of TA having potent free radical scavenging property. The results indicate that the extract could protect hepatic and cardiac tissues against Cd-induced oxidative stress mediated damages through antioxidant mechanism(s).

A dosimetric study of electron beam therapy vs. high-dose-rate mould brachytherapy in adjuvant treatment of non-melanoma skin carcinomas of the head and neck region.

PURPOSE: Radiation for superficial tumours of the head and neck region can be given either by brachytherapy or electrons. Brachytherapy (BT), due to rapid dose fall-off and minor set-up errors, should be superior to external beam radiotherapy (EBRT) for treatment of lesions in difficult locations such as the nose and earlobe. The present study is a dosimetric comparison of computed tomography (CT)-based mould brachytherapy treatment plans with 3D conformal electron beam therapy in the treatment of non-melanoma skin cancers (NMSC). MATERIAL AND METHODS: From December 2017 to November 2018 10 patients with NMSC of the head and neck region (forehead, nose, cheek) who underwent adjuvant radiation with HDR brachytherapy (BT) with a surface mould individual applicator were enrolled for analysis. We evaluated dose coverage by minimal dose to 90% of planning target volume (PTV, D90), volumes of PTV receiving 90-150% of prescribed dose (PD) (VPTV90-150), conformal index for 90% and 100% of PD (COIN90, COIN100), dose homogeneity index (DHI), dose nonuniformity ratio (DNR), and exposure of organs at risk (OARs) (eyes, lens, underlying bone and skin). Prospectively, we created CT-based treatment plans for electron beam therapy. We compared conformity (COIN90, COIN100), dose coverage of PTV (D90, VPTV90, VPTV100), volumes of body receiving 10-90% of PD (V10-V90), doses to OARs (D0.1cc and D2cc) of BT and electron plans. RESULTS: We obtained mean BT-DHI 0.81, BT-DNR 0.608, Electron-DHI 1.25. We observed no significant differences in VPTV90,100 and D90 between BT and electron beam. Mean BT-VPTV125,150 were significantly higher than Electron-VPTV100,125. COIN90 was superior for BT plans. CONCLUSIONS: CT-based surface mould brachytherapy results in better conformity of superficial lesions on small, irregular surfaces such as the nose and inner canthus than electrons with a slightly higher skin dose.

Protective effects of piperine against copper-ascorbate induced toxic injury to goat cardiac mitochondria in vitro.

Piperine, the main alkaloid of black pepper, Piper nigrum Linn., is an important Indian spice used in traditional food and medicine in India. In the present study, we investigated the antioxidant activities of piperine against copper-ascorbate induced toxic injury to mitochondria obtained from a goat heart, in vitro. Incubation of isolated cardiac mitochondria with copper-ascorbate resulted in elevated levels of lipid peroxidation and protein carbonylation of the mitochondrial membrane, a reduced level of mitochondrial GSH and altered status of antioxidant enzymes as well as decreased activities of pyruvate dehydrogenase and the Kreb's cycle enzymes, altered mitochondrial morphology, mitochondrial swelling, di-tyrosine level and mitochondrial DNA damage. All these changes were found to be ameliorated when the cardiac mitochondria were co-incubated with copper-ascorbate and piperine, in vitro. Piperine, in our in vitro experiments, was found to scavenge hydrogen peroxide, superoxide anion free radicals, hydroxyl radicals and DPPH radicals, in a chemically defined system, indicating that this compound may provide protection to cardiac mitochondria against copper-ascorbate induced toxic injury through its antioxidant activities. The results of this study suggest that piperine may be considered as a future therapeutic antioxidant and may be used singly or as a co-therapeutic in the treatment of diseases associated with mitochondrial oxidative stress.