A Monte Carlo simulation-based decision support system for radiation oncologists in the treatment of glioblastoma multiforme.

In the present research, we have developed a model-based crisp logic function statistical classifier decision support system supplemented with treatment planning systems for radiation oncologists in the treatment of glioblastoma multiforme (GBM). This system is based on Monte Carlo radiation transport simulation and it recreates visualization of treatment environments on mathematical anthropomorphic brain (MAB) phantoms. Energy deposition within tumour tissue and normal tissues are graded by quality audit factors which ensure planned dose delivery to tumour site thereby minimising damages to healthy tissues. The proposed novel methodology predicts tumour growth response to radiation therapy from a patient-specific medicine quality audit perspective. Validation of the study was achieved by recreating thirty-eight patient-specific mathematical anthropomorphic brain phantoms of treatment environments by taking into consideration density variation and composition of brain tissues. Dose computations accomplished through water phantom, tissue-equivalent head phantoms are neither cost-effective, nor patient-specific customized and is often less accurate. The above-highlighted drawbacks can be overcome by using open-source Electron Gamma Shower (EGSnrc) software and clinical case reports for MAB phantom synthesis which would result in accurate dosimetry with due consideration to the time factors. Considerable dose deviations occur at the tumour site for environments with intraventricular glioblastoma, haematoma, abscess, trapped air and cranial flaps leading to quality factors with a lower logic value of 0. Logic value of 1 depicts higher dose deposition within healthy tissues and also leptomeninges for majority of the environments which results in radiation-induced laceration.

Accelerated hypofractionated chemoradiation for locally advanced head and neck cancer during COVID 19 pandemic: A tertiary care experience.

PURPOSE: To assess the role of Accelerated Hypofractionated Chemoradiation for Locally Advanced Head & Neck squamous cell cancer (HNSCC) during COVID 19 pandemic. MATERIALS AND METHODS: Previously untreated 20 patients with locally advanced HNSCC (Oral cavity/oropharynx/larynx/hypopharynx) were treated with definitive hypofractionated radiotherapy of 60Gy in 25 fractions with concurrent cisplatin @35 mg/m2 once weekly for 5 weeks from March 2020 to November 2021. The patients were treated on 6MV LINAC with Volumetric modulated arc therapy (VMAT) by the Sequential boost technique and concurrent chemotherapy @35 mg/m2. All the patients received 48Gy in 20 fractions to low-risk volume (CTV LR) in Phase I followed by 12Gy in 5 fractions boost to High-risk volume (CTV HR) in Phase II. The organs at risk (OARs) were contoured and appropriate constraints were given considering the hypofractionated regimen. RESULTS: Out of 20 patients, most of the patients were Stage IV (15;75%) & stage III 20%, out of which (55%) 11 were of the oral cavity, (40%) 8 were of the oropharynx, and (5%) 1 of larynx. All patients were treated with 60Gy/25#/5 weeks with the majority of the patients (17;85%) completing their treatment in less than 45 days. The Median follow-up was of 214 days. The locoregional control at 6 Months was 55%. Maximum acute toxicity was grade 3 mucositis which was observed in 18 (90%) patients. Ryle's tube feeding was needed in 11 (55%) patient. Out of 20 patients, 5 patients did not receive concurrent chemotherapy, and 8 (40%) patients received all 5 cycles of chemotherapy. 7, 35% of the patients could not complete all 5 cycles of concurrent chemotherapy due to grade 3 mucositis. CONCLUSION: During a pandemic crisis with limited manpower & technical resources accelerated hypofractionated radiotherapy with concurrent chemotherapy can be considered a feasible therapeutic option for HNSCC which can significantly reduce the overall Treatment Time (OTT) with comparable local control and manageable toxicities.

Dose at posterior-inferior border of symphysis point: A predictor for vaginal stricture in cervical cancer.

PURPOSE: To study the effect of various dose-volume parameters on the severity of vaginal stricture (VS) and the correlation of the latter with the posterior-inferior border of symphysis (PIBS) points in locally advanced cervical cancer patients treated with concurrent chemoradiation and brachytherapy. METHODS AND MATERIALS: A prospective study was done on 45 histologically proven locally advanced cervical cancer patients between January 2020 and March 2021. All of them were treated with concurrent chemoradiation with 6 MV photon linear accelerator to a dose of 45 Gy/25 fractions in 5 weeks. Twenty-three patients were treated with intracavitary brachytherapy with a dose of 7 Gy/fraction/week for three fractions. Twenty-two patients were treated with interstitial brachytherapy, with 6 Gy/fraction for four fractions, each fraction 6 h apart. Grading of VS was done as per Common Terminology Criteria for Adverse Events version 5. RESULTS: The median followup was 21.5 months. About 37.8% of patients had VS with a median duration of 8.0 months (4.0-12 months). About 22.2% had Grade 1, 6.7% had Grade 2, and 8.9% had Grade 3 toxicity. Doses at PIBS and PIBS-2 points had no correlation with vaginal toxicity, however, the dose at PIBS+2 was significantly associated with VS (p = 0.004). The treated length of the vagina at the time of brachytherapy (p = 0.001), initial tumor volume (p = 0.009), and vaginal involvement after completion of external beam radiotherapy (EBRT) (p = 0.01) were also statistically significant with the development of VS of Grade 2 or more. CONCLUSIONS: Dose at PIBS + 2, treated length of the vagina with brachytherapy, initial tumor volume, and post-EBRT vaginal involvement are strong predictors for the severity of VS.

A prospective randomized comparison of simultaneous integrated boost with sequential boost intensity-modulated radiotherapy in locally advanced head and neck cancer.

Purpose: A comparison of simultaneous integrated boost (SIB) with sequential boost (SEQ) using intensity-modulated radiotherapy along with concurrent cisplatin in locally advanced head and neck cancer (HNC) was made with regard to their survival outcomes and toxicity profile. Materials and Methods: A total of 34 patients were enrolled between October 2016 and March 2019. They were randomized into two arms, SIB and SEQB. All patients were treated with 6 MV photon beam on Linear Accelerator with weekly concurrent cisplatin at 35 mg/m2. Overall survival (OS) and disease-free survival (DFS) were the primary end points and acute and late toxicities were the secondary end points. Results: The median follow-up period was 40.6 and 37.3 months for SIB and SEQB, respectively. At the end of 5 years, the median OS was 40.6 and 37.3 months (P = 0.947) and the median DFS was 35.1 and 37.3 months in the SIB and SEQB arms, respectively (P = 0.991). Complete response at 3 months was 64.7% and 76.5% and partial response was 23.5% and 17.6%, whereas progressive disease was 11.8% and 5.9% in SIB and SEQB arms, respectively. Acute dermatitis, mucositis, dysphagia, and salivary gland toxicities were higher in the SIB arm compared to the SEQB arm. Conclusion: SIB and SEQ arms were comparable in terms of OS and DFS. However, the acute toxicities were higher in the SIB arm, although the difference was not significant, compared to the SEQB arm.

Design and development of novel p-aminobenzoic acid derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer's disease.

Based on the quantitative structure-activity relationship (QSAR), some novel p-aminobenzoic acid derivatives as promising cholinesterase enzyme inhibitors were designed, synthesized, characterized and evaluated to enhance learning and memory. The in vitro enzyme kinetic study of the synthesized compounds revealed the type of inhibition on the respective acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The in vivo studies of the synthesized compounds exhibited significant reversal of cognitive deficits in the animal models of amnesia as compared to standard drug donepezil. Further, the ex vivo studies in the specific brain regions like the hippocampus, hypothalamus, and prefrontal cortex regions also exhibited AChE inhibition comparable to standard donepezil. The in silico molecular docking and dynamics simulations studies of the most potent compound 22 revealed the consensual interactions at the active site pocket of the AChE.

A comparison of six fractions per week chemoradiation versus five fractions per week of conventional chemoradiation in carcinoma cervix: A prospective controlled study.

AIMS: The standard of care for carcinoma cervix stage IB2-IVA is five fractions per week of radiotherapy (RT) with concurrent cisplatin. We compared the standard treatment with six fractions per week of RT with concurrent Cisplatin to see whether the later had improved survival outcomes with comparable toxicities. SETTINGS AND DESIGN: 46 patients of carcinoma cervix with stage IB2-IVAwere randomized into two arms. MATERIALS AND METHODS: Study arm: 46 Gy/23 fractions/26 days, 6 fractions/week with injection CDDP 40 mg/m2 and Control arm: 46 Gy/23 fractions/31 days, 5 fractions/week with injection Cisplatin 40mg/m2. Patients in both the arms received LDR brachytherapy to a dose of 29 Gy at point A. STATISTICAL ANALYSIS USED: The primary end points were disease-free survival (DFS) and overall survival (OS). Compliance to treatment and treatment toxicities were the secondary end points. P value ≤0.05 were considered significant. RESULTS: The study was carried out during June, 2014-April, 2015. Statistical analysis was done in May, 2019. Of 46 patients, 39 patients completed the treatment. The study and control arms had 17 and 22 patients, respectively. Median follow-up period is 45 months (range: 1-54 months). 3-year DFS rates and OS was 69.5% vs. 72.7% (P = 0.73) and 63% vs. 68% (P = 0.45) in study and in control arm, respectively. There was no significant difference in acute and late radiation toxicities between two arms. CONCLUSION: Chemoradiotherapy with six fractions per week seems feasible and equally efficacious in terms of survival outcomes and toxicity profile. Further prospective randomized controlled study is required to prove the merit of altered fractionation with concurrent cisplatin.

Polylactide-co-glycolide nanoparticles of antitubercular drugs: formulation, characterization and biodistribution studies.

BACKGROUND: The present study was designed to prepare and characterize poly lactide-co-glycolide nanoparticles of antitubercular drugs (ATDs) for delivery through oral route to alveolar macrophages. METHODS: Nanoparticles were prepared by double emulsification solvent evaporation method. Ex vivo and in vivo drug accumulation studies were performed in alveolar macrophages, harvested by broncheoalveolar lavaging. Internalization of nanoparticles was studied by confocal laser scanning microscopy. γ-scintigraphy imaging using technetium-99m was done to study the biodistribution pattern of nanoparticles. RESULTS: High intracellular concentrations of ATDs were observed in macrophages within 30 min of administration of nanoparticles. Intense radioactivity recorded in liver, spleen and lungs revealed uptake of nanoparticles in macrophages, abundantly present in mononuclear phagocyte system present in these organs. CONCLUSION: Targeted delivery of ATDs will help reduce dose and associated side effects including hepatotoxicity of ATDs. Further studies are required to assess the potential therapeutic advantages for treatment of TB.

Automated medical image segmentation techniques.

Accurate segmentation of medical images is a key step in contouring during radiotherapy planning. Computed topography (CT) and Magnetic resonance (MR) imaging are the most widely used radiographic techniques in diagnosis, clinical studies and treatment planning. This review provides details of automated segmentation methods, specifically discussed in the context of CT and MR images. The motive is to discuss the problems encountered in segmentation of CT and MR images, and the relative merits and limitations of methods currently available for segmentation of medical images.

Segmentation and classification of medical images using texture-primitive features: Application of BAM-type artificial neural network.

The objective of developing this software is to achieve auto-segmentation and tissue characterization. Therefore, the present algorithm has been designed and developed for analysis of medical images based on hybridization of syntactic and statistical approaches, using artificial neural network (ANN). This algorithm performs segmentation and classification as is done in human vision system, which recognizes objects; perceives depth; identifies different textures, curved surfaces, or a surface inclination by texture information and brightness. The analysis of medical image is directly based on four steps: 1) image filtering, 2) segmentation, 3) feature extraction, and 4) analysis of extracted features by pattern recognition system or classifier. In this paper, an attempt has been made to present an approach for soft tissue characterization utilizing texture-primitive features with ANN as segmentation and classifier tool. The present approach directly combines second, third, and fourth steps into one algorithm. This is a semisupervised approach in which supervision is involved only at the level of defining texture-primitive cell; afterwards, algorithm itself scans the whole image and performs the segmentation and classification in unsupervised mode. The algorithm was first tested on Markov textures, and the success rate achieved in classification was 100%; further, the algorithm was able to give results on the test images impregnated with distorted Markov texture cell. In addition to this, the output also indicated the level of distortion in distorted Markov texture cell as compared to standard Markov texture cell. Finally, algorithm was applied to selected medical images for segmentation and classification. Results were in agreement with those with manual segmentation and were clinically correlated.