Browsing by Author "Lalit M. Aggarwal"

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A Monte Carlo simulation-based decision support system for radiation oncologists in the treatment of glioblastoma multiforme
(Springer Science and Business Media Deutschland GmbH, 2024) C. Praveen Kumar; Lalit M. Aggarwal; Saju Bhasi; Neeraj Sharma
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. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
A prospective randomized comparison of simultaneous integrated boost with sequential boost intensity-modulated radiotherapy in locally advanced head and neck cancer
(Wolters Kluwer Medknow Publications, 2022) Nilesh Mani; Sushil K. Aggarwal; Ishan Kumar; Abhijit Mandal; Garima Jaiswal; Rakesh Ranjan; Anil K. Jaiswal; Neha Gupta; Ankita Singh; Ankur Mourya; Lalit M. Aggarwal; Sunil Choudhary
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/m 2. 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. © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
Accelerated hypofractionated chemoradiation for locally advanced head and neck cancer during COVID 19 pandemic: A tertiary care experience
(Wolters Kluwer Medknow Publications, 2024) Sumit Agarwal; Isha Jaiswal; Uday P. Shahi; Abhijit Mandal; Lalit M. Aggarwal; Ankita Singh; Anil Jaiswal; Nandlal Yadawa
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. © 2023 Journal of Cancer Research and Therapeutics.
Automatic Deformity Estimation for Thoracic Section Between Inhale and Exhale Positions
(Springer India, 2016) Ali Imam Abidi; Sanjay Kumar Singh; Lalit M. Aggarwal
Corresponding control point pairs or landmarks in images can be used to define the deformation with respect to time, point of view or modality. Manual definition of the number of control points in an image, enough to define all kinds of deformation is a tedious task. Hence, automatic definition of control points is the way forward taken in this proposed work. The paper proposes an automatic registration process for tracing of the deformity path of the thoracic region based on feature detector speeded up robust feature (SURF) and moving least squares (MLS). The set of control points on the images is defined by its feature set which is obtained by using the SURF detector, which serves as input for MLS algorithm to trace the deformations of the image (thoracic image in this case). The credibility and performance of the above proposed method is demonstrated by its outstanding experimental results. © 2016, The National Academy of Sciences, India.
Design and development of novel p-aminobenzoic acid derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer's disease
(Academic Press Inc., 2019) Sushant K. Shrivastava; Saurabh K. Sinha; Pavan Srivastava; Prabhash N. Tripathi; Piyoosh Sharma; Manish K. Tripathi; Avanish Tripathi; Priyanka K. Choubey; Digambar K. Waiker; Lalit M. Aggarwal; Manish Dixit; Subhash C. Kheruka; Sanjay Gambhir; Sharmila Shankar; Rakesh K. Srivastava
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. © 2018 Elsevier Inc.
Dose at posterior-inferior border of symphysis point: A predictor for vaginal stricture in cervical cancer
(Elsevier Inc., 2023) Ankita Singh; Nilesh Mani; Lalit M. Aggarwal; Sumit Agarwal; Ankur Mourya; Ashish Verma; Antara Bagchi; Neha Gupta; Sunil Choudhary
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. © 2023 American Brachytherapy Society
Monte carlo calculation of 6 MV varian linac photon beam spectral characteristics using the BEAM code
(Research India Publications, 2016) Ankit Kajaria; Neeraj Sharma; Shiru Sharma; Satyajit Pradhan; Abhijit Mandal; Lalit M. Aggarwal
In this study the BEAMnrc Monte Carlo (MC) code is used to simulate 6 MV photon beam as the MC methods are consider to be most reliable and accurate to evaluate the radiation beam characteristics. In this work the MC simulation model is used to calculate depth-dose curves and contribution of contaminant electron to it. We also calculated photon spectra, photon average energy distributions, photon energy fluence spectra, contaminant electron spectra at 100 cm source to surface distance. The sensitivity of these parameters has been analyzed in detail. The contribution of electrons to the central-axis depth-dose was calculated and it was observed that its contribution is less than 7% of maximum total dose at surface, while at the depth of maximum dose (dmax) its contribution was less than 3% of maximum total dose for 10×10 cm2 field sizes. The photon energy fluence spectra are separated into direct and scatter components from the primary collimator, flattening filter and the adjustable collimators. The contribution of direct photons to the total photon energy fluence is about 97% and the scatter contributions to the total photon energy fluence from the primary collimator and flattening filter are typically less than 3% and scatter contributions from jaws is less than 0. 30% to the total photon energy fluence for 10×10 cm2 fields size. The calculated and measured depth-dose data agree within 1% of local dose, and 1. 0 mm in depth at all depths and field sizes which gave enough confidence that MC Simulations could be used to simulate the 6 MV photon beam. Our study shows that both photon and electron fluence spectra strongly depend upon field size. Most of the scatter energy fluence of photon comes from flattening filter and primary collimator. Beam hardening effects of flattening filter have also been verified by the study of average energy distribution. © Research India Publications.
Negatively charged liposomes of sertraline hydrochloride: Formulation, characterization and pharmacokinetic studies
(Editions de Sante, 2020) Tejpratap Chauhan; Varsha Rani; Bhupendra Sahu; Adity Sharma; Subhash Chand Kheruka; Sanjay Gambhir; Veeresh Dube; Lalit M. Aggarwal; Ruchi Chawla
The present study was carried out with an objective to study the extent of delivery of negatively charged liposomes of sertraline hydrochloride to brain via intravenous route for treatment of depressive –like symptoms. Liposomes of sertraline hydrochloride were formulated by film hydration technique using cholesterol, hydrogenated soya phosphatidylcholine-L-α-phosphatidylcholine, and distearoyl phosphatidyl glycerol sodium. Uniform sized vesicles with porous surface morphology with vesicle size of 151.59 nm were prepared. Radioactive imaging performed using 99mTcO4 showed ~5% of uptake of labelled liposomes in brain within 2 h of administration. On administration of liposomes and free drug suspension, approximately, 205.06 ng/ml and 87.18 ng/ml of sertraline were estimated in brain at 36 h. The liposomes can be transported by transcelluar transport which includes phagocytosis and the use of phosphatidylcholine enhances macrophage internalization and delivery to brain. The study indicated significantly higher concentration of sertraline in brain after 36 h, on administration of liposomes as compared to free sertraline suspension. © 2020 Elsevier B.V.
Polylactide-co-glycolide nanoparticles of antitubercular drugs: Formulation, characterization and biodistribution studies
(Future Science Ltd, 2014) Ruchi Chawla; Harshendra S. Solanki; Subhash Chand Kheruka; Sanjay Gambhir; Veeresh Dube; Lalit M. Aggarwal; Brahmeshwar Mishra
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. © 2014 Future Science Ltd.
Segmentation of medical images using simulated annealing based fuzzy C means algorithm
(Inderscience Publishers, 2009) Neeraj Sharma; Amit K. Ray; Shiru Sharma; K.K. Shukla; Lalit M. Aggarwal; Satyajit Pradhan
Accurate segmentation is desirable for analysis and diagnosis of medical images. This study provides methodology for fully automated simulated annealing based fuzzy c-means algorithm, modelled as graph search method. The approach is unsupervised based on pixel clustering using textural features. The virtually training free algorithm needs initial temperature and cooling rate as input parameters. Experimentation on more than 180 MR and CT images for different parameter values, has suggested the best-suited values for accurate segmentation. An overall 97% correct segmentation has been achieved. The results, evaluated by radiologists, are of clinical importance for segmentation and classification of Region of Interest. Copyright © 2009, Inderscience Publishers.
Study of unflattened photon beams shaped by multileaf collimator using BEAMnrc code
(Cambridge University Press, 2016) Ankit Kajaria; Neeraj Sharma; Shiru Sharma; Satyajit Pradhan; Abhijit Mandal; Lalit M. Aggarwal
Purpose: In our study basic dosimetric properties of a flattening filter free 6 MV photon beam shaped by multileaf collimators (MLC) is examined using the Monte Carlo (MC) method. Methods and materials: BEAMnrc code was used to make a MC simulation model for 6 MV photon beam based on Varian Clinic 600 unique performance linac, operated with and without a flattening filter in beam line. Dosimetric features including central axis depth dose, beam profiles, photon and electron spectra were calculated and compared for flattened and unflattened cases. Results: Dosimetric field size and penumbra were found to be smaller for unflattened beam, and the decrease in field size was less for MLC shaped in comparison with jaw-shaped unflattened beam. Increase in dose rate of >2.4 times was observed for unflattened beam indicating a shorter beam delivery time for treatment. MLC leakage was found to decrease significantly when the flattening filter was removed from the beam line. The total scatter factor showed slower deviation with field sizes for unflattened beam indicating a reduced head scatter. Conclusions: Our study demonstrated that improved accelerator characteristics can be achieved by removing flattening filter from beam line. © Cambridge University Press 2016.
Unified Dosimetry Quality Audit Index: an integrated Monte Carlo model-based quality assurance ranking for radiotherapy treatment of glioblastoma multiforme
(Taylor and Francis Ltd., 2023) Praveen Kumar C; Lalit M. Aggarwal; Saju Bhasi; Neeraj Sharma
In the present research, we have developed a Unified Dosimetry Quality Audit Index (UDQAI) decision support system supplemented with treatment planning systems for radiation oncologists. This will aid the radiotherapy treatment of Glioblastoma Multiforme and is based on the Integrated Monte Carlo Model (IMC). IMC model is a quality assurance strategy for the computation of total dose, scatter dose deposition at the GBM site and healthy tissues/layers within the brain. It is a combination of Proliferation-Hypoxia-Invasion-Necrosis-Angiogenesis-Radiotherapy-Quality Assurance model, Radiation-induced damage-Quality Assurance model, Boltzmann radiation transport, Talaraich Tournoux image coordinate system for positioning of the tumour from the CT image and GBM treatment environments/patient case reports. The IMC model was validated by recreating GBM patient treatment environments on a novel computational heterogeneous phantom, the Mathematical Anthropomorphic Brain (MAB) phantom. Dose computations accomplished through water phantom, tissue-equivalent head phantoms are neither cost effective; nor patient-specific and are non-customised and less accurate. Thirty-Eight patient-specific GBM treatment environments were recreated on the MAB phantom. MAB phantom synthesis requires mimicking real human brain tissues/layers. Open-source protein databases such as UniProt, Swiss-model and Peptide were atlas employed to compute the elemental composition of different brain layers/tissues. Brain layers and tissues were synthesised as slabs using the Constructive Solid Geometry technique within the MAB phantom on the Electron Gamma Shower radiation transport platform. Phantom slab dimensions were computed by superimposing CT scan images of the brain with GBM and associated comorbidities on Talairach-Tournoux coordinate system. Slab surfaces of the phantom were defined by constructive solid geometry approach using quadratic equations. Energy deposition inside different slabs of phantom is calculated by Analog Monte Carlo game. Computed total dose and scatter dose deposition within the tumour and normal tissues/brain layers were graded by UDQAI which ensures planned dose delivery to the tumour site for radiation-induced cancer cell death minimising healthy tissue damages. The results of the present experimentation show that the proposed framework is promising and outperforms other recent deep learning-based decision systems. Deep learning-based decision systems are a hidden process which is unaware of the physical transport process of charged particles. UDQAI classification of treatment environments predicts that 76.32% of the total environs deposited a substantial amount of dose to the GBM locus. During treatment, healthy tissues and brain layers receive a part of transported energy. This fact is reinforced by the average deviation at the GBM site −8.2% on the contrary, healthy tissues encircling GBM reported −3.909%. These encouraging results would pave the way for the development of a biomathematical tumour growth model and Monte Carlo radiation transport-linked decision assist algorithm for radiation oncologists in the near future. © 2022 Informa UK Limited, trading as Taylor & Francis Group.
Variation in applicator positions during interfraction high-dose rate brachytherapy in carcinoma cervix: Dosimetric evaluation
(2013) Kamlesh Passi; Lalit M. Aggarwal; Rajesh Vashistha; Bikramjit Singh; Parveen Kaur; Sureshchandra J. Gupta; Than S. Kehwar
Purpose This study was designed to study the variations in different geometrical and dosimetric parameters. Materials and methods In this study, two groups comprises 21 and 28 patients, who were treated with 9·5 Gy × 2 Fx and 7·5 Gy × 3 Fx, respectively, using microselectron high-dose rate (HDR) remote control unit. All patients were analysed using orthogonal radiographs to evaluate variations in different parameters. Results Variations in different parameters are more in Group II patients than in Group I patients, which show that the variation in geometrical and dosimetrical parameters increases with increasing HDR number of fractions. Conclusion In the reporting of an outcome of multiple fractionation of HDR treatments resultant dosimetric parameters must be evaluated and must be used for clinical interpretation. Copyright © Cambridge University Press 2013.