Evolution of Bioelectric Membrane Potentials: Implications in Cancer Pathogenesis and Therapeutic Strategies.

Electrophysiology typically deals with the electrical properties of excitable cells like neurons and muscles. However, all other cells (non-excitable) also possess bioelectric membrane potentials for intracellular and extracellular communications. These membrane potentials are generated by different ions present in fluids available in and outside the cell, playing a vital role in communication and coordination between the cell and its organelles. Bioelectric membrane potential variations disturb cellular ionic homeostasis and are characteristic of many diseases, including cancers. A rapidly increasing interest has emerged in sorting out the electrophysiology of cancer cells. Compared to healthy cells, the distinct electrical properties exhibited by cancer cells offer a unique way of understanding cancer development, migration, and progression. Decoding the altered bioelectric signals influenced by fluctuating electric fields benefits understanding cancer more closely. While cancer research has predominantly focussed on genetic and molecular traits, the delicate area of electrophysiological characteristics has increasingly gained prominence. This review explores the historical exploration of electrophysiology in the context of cancer cells, shedding light on how alterations in bioelectric membrane potentials, mediated by ion channels and gap junctions, contribute to the pathophysiology of cancer.

Body Composition Analysis Techniques and Its Application in Oncology: A Review.

The oncology community has shown growing interest to understand how body composition measures can be utilized to improve cancer treatment and survivorship care for about 20 million individuals diagnosed with cancer annually. Recent observational studies demonstrate that muscle and adipose tissue distribution are risk factors for clinical outcomes such as postoperative complications, and worse overall survival. There is an emergent recognition that body mass index (BMI) is neither adequate to identify patients with adverse health outcomes due to poor muscle health or excess adiposity, nor does BMI accurately classify the distribution of adiposity. Abdominal CT is a most frequently imaging examination for a wide variety of clinical indications, but it is only used to diagnose the immediate problem. Additionally, each CT examination contains very robust data on body composition which generally goes unused in routine clinical practice. The field is eager to identify therapeutic interventions that modify body composition and reduce the incidence of poor clinical outcomes in this population. Large scale population based screening is feasible now by making all of these relevant biometric measures fully automated through the use of artificial intelligence algorithms, which provide rapid and objective assessment.

Radiation dosimetry and repair kinetics of DNA damage foci in mouse pachytene spermatocyte and round spermatid stages.

Accurate quantification of DNA double strand breaks (DSB) in testicular germ cells is difficult because of cellular heterogeneity and the presence of endogenous γH2AX. Here, we used confocal microscopy to quantify DNA damage and repair kinetics following γ-irradiation (0.5-4 Gy) in three major mouse male germ cell stages, early and late pachytene spermatocytes and round spermatids (RSs), following a defined post irradiation time course. Dose-response curves showing linear best fit validated γH2AX focus as a rapid biodosimetric tool in these substages in response to whole body in vivo exposure. Stage specific foci yield/dose and repair kinetics demonstrated differential radiosensitivity and repair efficiency: early pachytenes (EP) repaired most rapidly and completely followed by late pachytene (LP) and RSs. Repair kinetics for all three stages followed 'exponential decay' in response to each radiation dose. In pachytenes immediate colocalisation of γH2AX and 53BP1, which participates in non-homologous end-joining repair pathway, was followed by dissociation from the major focal area of γH2AX by 4 h demonstrating ongoing DSB repair. These results confirm the differential radiosensitivity and repair kinetics of DSBs in male germ cells at different stages. Taken together, our results provide a simple and accurate method for assessing DNA damage and repair kinetics during spermatogenesis.

Carbon-based brilliance: a novel approach to renewable energy in radiotherapy centers.

The energy produced from other sources which does neither come from fossil fuels nor contribute in the production of any greenhouse effects that causes climate changes is called as 'Alternative Energy'. Since our world's primary energy sources such as coal, oil and natural gases are exploited to a greater extent, we are in an urge to switch to an alternative energy. Scattered radiation, a common byproduct in radiation therapy and diagnostic radiology, presents a unique opportunity in the realm of alternative energy. As a potential source of interference, scattered radiation can be repurposed to contribute to sustainable energy solutions. Addressing the issue of scattered radiation wastage and utilizing it for alternative energy, an activated carbon-based solar cell emerges as a solution. This solar cell, a conventional one in which cadmium Telluride is replaced by coconut shell based carbon material, has the potential in producing a significant amount of electrical energy by utilizing scattered radiation from radiotherapy and radiology machines. Furthermore, this activated carbon based-material undergoes thorough characterization into various teletherapy and radiology machines, and it can be seamlessly integrated into clinical practices.

A mathematical model to predict the different isodose volumes using TRAK value in HDR intracavitary brachytherapy for revised Manchester and ICRU-89 based Point A plans using computer tomography images.

Purpose: To find out the simple relationship between Total Reference Air Kerma (TRAK) and various isodose volumes. Calculated isodose volumes were compared with experimental data for revised Manchester and International Commission on Radiation Units and measurements (ICRU)-89 Point A-based treatment plans. The accuracy of the formula was compared with the results of other relationships available in the literature. Materials and Methods: Dosimetric data from 62 intracavitary brachytherapy (ICBT) treatment plans of 31 patients with cervical cancer were studied. Each patient had treatment plans normalized to revised Manchester and ICRU-89 Points A (Aflange and Aicru89). For each treatment plan, TRAK values, V350, V700, V1050, and V1400 were obtained. The modeling curve was plotted between Isodose volume (Vd) and the ratio of d/TRAK obtained from Aflange plans to get a mathematical relation. The results of this formula were compared with the experimental data and outcomes of other formulas available in the literature. A paired-sample t-test was performed to assess the statistical significance. Results: In the case of revised Manchester-based Aflange normalization plans, the mean isodose volume of V350, V700, V1050, and V1400 were 285.98 ± 32.3 cm3, 101.96 ± 10.63 cm3, 52.71 ± 4.72 cm3, and 31.44 ± 2.33 cm3 respectively. Likewise, for ICRU-89 based Aicru89 normalization plans, the mean isodose volumes of V350, V700, V1050, and V1400 were 304.11 ± 26.17 cm3, 108.88 ± 8.29 cm3, 56.62 ± 3.69 cm3 and 34 ± 2.23 cm3 respectively. The mean difference was significant. The Mathematical relationship developed was [INLINE:1]. No correlation was found between TRAK and D0.1cm3,D2cm3 for organs at risk. Conclusions: The developed formula calculated isodose volumes within the accuracy of ± 3% in ICBT plans.

Feasibility of using polytetrafluoroethylene flexible implant tube for interstitial brachytherapy patients.

PURPOSE: To design the different Polytetrafluoroethylene (PTFE) based flexible implant tubes using an in-house developed device and to evaluate them for High dose rate (HDR) interstitial brachytherapy using computer tomography images. METHODS AND MATERIALS: PTFE hollow tube having a 2 mm (6 French) outer diameter (OD) and 1.4 mm inner diameter (ID) was used to design in-house single and/or double leader flexible catheters for interstitial brachytherapy implant. An in-house Plastic Wire Drawing Plate (PWDP) machine was developed. Customization of PTFE hollow flexible implant tube (FIT) was done through PWDP. Different percentages of BaSO4 (5%, 10%, & 15%) were added to Nylon 6 to make radiopaque button. Various quality assurance tests were performed with the PTFE tubes implanted in the brinjal (phantom) before using them on the patients. That is, coupling of brachytherapy machine transfer tube with flexible PTFE Tubes, CT scan artifacts, tube kinks, breast template, and free-hand compatibility. RESULTS: With the help of the PWDP machine, plastic wires of different lengths were made for single leader and double leader tubes. The different plastic leader ends of 1 cm to 50 cm lengths having 1 mm diameter were created. The radiopaque button of Nylon 6 in circular shape having 1 cm diameter and 0.5 cm thick was created. Developed radiopaque buttons were visible on CT scan images as well as on radiograph images. CONCLUSIONS: PTFE tubes of the desired length can be made depending upon the size of the brachytherapy implant and are inexpensive than commercially available flexible implant tubes.

Evolution of Brachytherapy Applicators for the Treatment of Cervical Cancer.

Brachytherapy applicators have come a long way since Danlos developed early intracavitary applicators to treat cervical cancer patients. Therefore, this review will help in the neoteric designs of intracavitary applicators. A detailed literature survey of the gynecological brachytherapy applicators from the era of preloading to conceptual intensity-modulated brachytherapy applicators has been carried out. Depending on the extent of the disease and patient anatomy, the selection of brachytherapy applicators plays a pivotal role in the treatment of cervical cancer. Furthermore, the selection of the applicators is also based on the imaging modalities to be used for applicator reconstruction and treatment planning. Dose acceleration in the target and reduction in nearby organs at risk can be optimized using an applicator having the capabilities of intensity-modulated brachytherapy. Now, three-dimensional printed applicators are used for patient-specific tailor-made treatment and they are fast replacing the old conventional applicators. Newer advancements in technology have greatly influenced the neoteric designs of intracavitary brachytherapy applicators.

Influence of adjuvant therapy on pattern of failure and survival in curatively resected gallbladder carcinoma.

PURPOSE: The study was done to evaluate the role of adjuvant therapy in curatively resected Stage II and III gallbladder carcinoma (GBC). MATERIALS AND METHODS: This was a retrospective analysis of patients of GBC registered between 2008 and 2017 in outpatient department of a tertiary cancer hospital in India. Patients who had any of the following adjuvant treatment after radical surgery: (a) external beam radiotherapy (RT) alone, (b) chemotherapy (CT) alone, and (c) RT with CT (CRT) were considered for the study. RESULTS: A total of fifty patients could meet the selection criteria. It was seen that seven patients were treated with RT, 20 with CT, and 23 with CRT. Median follow-up for patients who were alive was 26.7 months. Nineteen patients had locoregional failure while eight had distant failure. Patients treated with CRT had a significantly better mean overall survival compared to those treated with RT or CT (44.0 months, 12.5 months, and 15.1 months, respectively; P = 0.003). Similarly, mean disease-free survival was superior in CRT arm compared to RT and CT arms (43.6 months, 9.6 months, and 12.4 months, respectively; P = 0.002). CONCLUSIONS: Adjuvant CRT had better survival outcome compared to patients treated with either RT or CT with Stage II and III disease after curative cholecystectomy.

A comparison between revised Manchester Point A and ICRU-89-recommended Point A definition absorbed-dose reporting using CT images in intracavitary brachytherapy for patients with cervical carcinoma.

PURPOSE: This study is a comparison between revised Manchester Point A and International Commission on Radiation Units and measurements (ICRU) 89 report-recommended Point A absorbed-dose reporting in intracavitary brachytherapy for patients with cervical carcinoma. METHODS AND MATERIALS: The retrospective dosimetric study is based on the data of 32 patients with cervical carcinoma treated with high-dose-rate brachytherapy. Patients received 21 Gy in three fractions (7.0 Gy X three fractions) to Point A (Aflange, revised Manchester definition). All the patients were replanned with a new Point A (Aicru89) defined on CT images as per the American Brachytherapy Society/ICRU-89. The data collected were compared with the data obtained from Point A (Aflange). RESULTS: When using the Aflange plan normalization method, the mean dose of 0.1 cc, 1 cc, and 2 cc bladder volumes was 820.79 ± 207.47 cGy, 654.66 ± 152.69 cGy, and 588.91 ± 136.35 cGy, respectively. Likewise, when using the ICRU-89 Point Aicru89 normalization method, the mean dose of 0.1 cc, 1 cc, and 2 cc bladder volumes was 869.30 ± 224.67 cGy, 693.24 ± 166.20 cGy, and 616.61 ± 150.32 cGy, respectively. For the rectum, Point Aflange normalization plans, the mean dose of 0.1 cc, 1 cc, and 2 cc volumes was 589.37 ± 163.26 cGy, 487.51 ± 126.03 cGy, and 442.70 ± 111.43 cGy, respectively. Likewise, using the Aicru89 plan, the mean 0.1 cc, 1 cc, and 2 cc rectum volume was 625.07 ± 171.31 cGy, 517.50 ± 131.05 cGy, 464.94 ± 121.81 cGy, respectively. The statistical mean difference of Total Reference Air Kerma rate, V100 (cc), bladder, rectum and sigmoid, was found significant. CONCLUSIONS: It has been found that the position of revised Manchester (Aflange) and ICRU-89 Point A does not match on CT images/radiograph, which resulted in variation in doses to the tumor, V100 (cc), organ at risk, and Total Reference Air Kerma.

An assessment of serum oxidative stress and antioxidant parameters in patients undergoing treatment for cervical cancer.

OBJECTIVES: Oxidative stress and antioxidants are involved in all aspects of cervical cancer. The present study evaluated serum levels of oxidative stress and antioxidant biomarkers in cervical cancer patients and healthy controls. Moreover, the effect of Concurrent chemoradiotherapy (CCRT) on these biomarkers and their association with treatment outcome was investigated. DESIGN: This study included ninety-seven cervical cancer patients and thirty controls. Three oxidative stress parameters (8-hydroxy-2-deoxyguanosine, Protein Carbonyl, and Malondialdehyde) and four antioxidant parameters (Superoxide Dismutase, Catalase, Glutathione Peroxidase, and Total Antioxidant Status) were measured. The analysis was conducted using repeated measures ANOVA for comparing among the phases (before, during, and follow-up) of treatment. The control group was compared using the Dunnet test. Logistic regression analysis was also conducted between oxidative stress and antioxidant parameters to study their association. RESULTS: Significant rises in oxidative damage markers were observed in cervical cancer patients of all stages, compared to controls. There was a further increase in oxidative stress markers during CCRT among complete responders. However, among non-responders, the oxidative stress biomarkers like Protein Carbonyl and Malondialdehyde were unaltered during CCRT. Simultaneously, there was a significant decrease in antioxidant parameters in cervical cancer patients of all stages compared to controls. During CCRT, antioxidant levels continuously depleted among complete responders. Nevertheless, in non-responders, antioxidant parameters like Superoxide Dismutase and Total Antioxidant Status were consistent. The oxidative stress markers and antioxidant parameters normalized among complete responders at six months follow up. While in non-responders, the normalization of these parameters was not observed. CONCLUSION: Our results indicate that increased oxidative stress and diminished antioxidants among patients were associated with carcinoma cervix. Induced oxidative stress and decreased antioxidant parameters during CCRT among the complete responders show the treatment's efficacy. Oxidant-antioxidant profile merits investigation as markers of diagnosis, treatment response, survival, and recurrence in extensive prospective studies.

Diagnostic and prognostic application of Raman spectroscopy in carcinoma cervix: A biomolecular approach.

Blood serum samples from 63 cervical cancer patients and 30 controls were collected at three different phases of the treatment (i.e. before, during, and at follow up). The spectra of serum samples from control as well as patients were classified into different groups using principal component analysis (PCA) and linear discriminant analysis (LDA) based on different phases of treatment using R software. The spectra of blood serum samples have shown the distinct changes and differences compared with each other in the profile of various biochemical parameters. The sensitivity (92.5%) and specificity (85%) were observed maximum between control and cervical cancer patients (before treatment). Between different phases of treatment, the sensitivity and specificity were less but, all accuracies of detection and classification reached above 50%. This method can be considered as a screening method for detection and treatment monitoring.

Comparison of two hypofractionated radiotherapy schedules in locally advanced postmastectomy breast cancer patients.

INTRODUCTION: The role of hypofractionated radiotherapy (HFRT) in postmastectomy breast cancer patients is not well established. This study was done to establish the role of two different HFRT schedules in the treatment of chest wall and regional lymph nodes after mastectomy. MATERIALS AND METHODS: Between 2012 and 2016, consecutively registered patients of locally advanced breast cancer patients having undergone mastectomy and adjuvant radiotherapy (RT) at a tertiary cancer center were analyzed. Locoregional recurrence (LRR) was the primary endpoint, whereas overall survival (OS), disease-free survival (DFS), and both acute and late adverse events were secondary endpoints. RESULTS: A total of 34 patients who were treated with 39 Gy in 13 fractions over 2½ weeks and 35 patients who were treated with 40 Gy in 15 fractions over 3 weeks were identified. The median follow-up period was 47 months and 63.5 months in the 39 Gy and 40 Gy arms, respectively. LRR was seen in 11.8% and 8.6% of patients in the 39 Gy and 40 Gy arms, respectively. OS at 4 years was 66% and 71.5% in the 39 Gy and 40 Gy arms, respectively. The mean DFS for 39 Gy and 40 Gy arms was 43.6 months and 66.4 months, respectively (P = 0.822). Acute skin toxicity was similar in the two groups. Arm edema was significantly more in the 40 Gy arm. CONCLUSION: The two HFRT schedules are equivalent to each other in terms of survival outcomes. Arm edema is higher with 40 Gy arm as compared to 39 Gy arm.

Evaluation of single-photon emission computed tomography images obtained with and without copper filter by segmentation.

BACKGROUND: Measurement of accurate attenuation of photon flux in tissue is important to obtain reconstructed images using single-photon emission computed tomography (SPECT). Computed tomography (CT) scanner provides attenuation correction data for SPECT as well as anatomic information for diagnostic purposes. Segmentation is a process of dividing an image into regions having similar properties such as gray level, color, texture, brightness, and contrast. Image segmentation is an important tool for evaluation of medical images. X-ray beam used in CT scan is poly-energetic; therefore, we have used a copper filter to remove the low energy X-rays for obtaining correct attenuation factor. Images obtained with and without filters were quantitatively evaluated by segmentation method to avoid human error. MATERIALS AND METHODS: Axial images of AAPM CT phantom were acquired with 3 mm copper filter (low intensity) and without copper filter (high intensity) using low-dose CT (140 kvp and 2.5 mA) of SPECT/CT system (Hawkeye, GE Healthcare). For segmentation Simulated Annealing Based Fuzzy c-means, algorithm is applied. Quantitative measurement of quality is done based on universal image quality index. Further, for the validation of attenuation correction map of filtered CT images, Jaszczak SPECT phantom was filled with 500 MBq of (99m)Tc and SPECT study was acquired. Low dose CT images were acquired for attenuation correction to be used for reconstruction of SPECT images. Another set of CT images were acquired after applying additional 3 mm copper filter. Two sets of axial SPECT images were reconstructed using attenuation map from both the CT images obtained without and with a filter. RESULTS AND CONCLUSIONS: When we applied Simulated Annealing Based Fuzzy c-means segmentation on both the CT images, the CT images with filter shows remarkable improvement and all the six section of the spheres in the Jaszczak SPECT phantom were clearly visualized.

An investigation of a sinogram discontinuity artifact on myocardial perfusion imaging.

UNLABELLED: Our purpose was to find out the cause of an unusual distinct break seen on a patient's sinogram despite within-tolerance results on all quality assurance tests during myocardial perfusion imaging (MPI) and corrective measures. METHODS: SPECT quality control is a prerequisite to obtaining high-quality diagnostic images. Daily uniformity and energy-peaking tests and weekly center-of-rotation (COR) tests are run to check the performance of the SPECT system. A distinct break in the sinogram of an MPI study was noticed for 1 patient, despite routine quality control tests that showed the system to be well within tolerance limits. Critical inspection of the γ-camera revealed that the 2 detector heads did not make complete contact with each other at a 90° position and that a gap of as much as 10.0 mm was left between the 2 edges of the detectors even though COR testing showed the system to be within tolerance limits. After this gap had been minimized (-10-mm position), the MPI study of this patient was repeated. RESULTS: Reduction of the gap between detectors corrected the sinogram discontinuity. On the MPI study, the break in the sinogram existed because the 2 detectors were not acquiring the data at the same position in their useful fields of view. When one of the detectors was tilted to exactly 45°, the gap was reduced and the data were acquired at the same useful field of view for both detectors. CONCLUSION: The sinogram artifact may arise even after perfect COR calibration, and in the reported case, the discontinuity in the sinogram was rectified by correcting the angle of the detectors. Meticulous investigation for artifacts must be performed to minimize the probability of false results.

A new method to correct the attenuation map in simultaneous transmission/emission tomography using Gd/Ga radioisotopes.

Reconstruction of the tomographic images without attenuation correction can cause erroneously high count densities and reduced image contrast in low attenuation regions. In order to solve the problem of photon attenuation, one needs to know the attenuation coefficient for the individual patient being studied. Therefore, we made an attempt to correct the attenuation map in simultaneous transmission/emission tomography with (153)Gd/(67)Ga using maximum likelihood method using the expectation maximization (ML-EM) algorithm to correct the transmission window for both the spillover and downscatter. Spillover fraction, scatter fraction and parameters for the scatter function (A, b and c) were determined experimentally and optimized using the optimization program written in IDL based on simplex theory. All measurements were performed on a Vertex gamma camera using the anthropomorphic thorax phantom for validation of data obtained by the proposed method. It was observed that without spillover and downscatter correction, the mean counts were 19.29 in liver and 26.90 in lung, whereas after after applying the corrections, the mean counts were reduced to 3.80 and 15.10 in liver and lung, respectively, which were close to true mean counts (liver 2.15 and lung 14.89). In this proposed method, we introduced the set of F(t)(spillover) and K(t)(downscatter) to account for the variations in projection pixels (f(t) and k(t)) with the density and thickness. The F(t) and K(t) were determined using the transmission data by an iterative process. The quantitative error was reduced by 98.0% for lung and 90.0% for liver when the corrected transmission images were obtained after the subtraction of spillover and downscatter fraction.

Experience of wireless local area network in a radiation oncology department.

The aim of this work is to develop a wireless local area network (LAN) between different types of users (Radiation Oncologists, Radiological Physicists, Radiation Technologists, etc) for efficient patient data management and to made easy the availability of information (chair side) to improve the quality of patient care in Radiation Oncology department. We have used mobile workstations (Laptops) and stationary workstations, all equipped with wireless-fidelity (Wi-Fi) access. Wireless standard 802.11g (as recommended by Institute of Electrical and Electronic Engineers (IEEE, Piscataway, NJ) has been used. The wireless networking was configured with the Service Set Identifier (SSID), Media Access Control (MAC) address filtering, and Wired Equivalent Privacy (WEP) network securities. We are successfully using this wireless network in sharing the indigenously developed patient information management software. The proper selection of the hardware and the software combined with a secure wireless LAN setup will lead to a more efficient and productive radiation oncology department.

Workload modeling for teletherapy unit.

AIMS: This study aims to derive a radiotherapy workload model using a prospectively collected dataset of patient and treatment information from a teletherapy treatment unit. MATERIALS AND METHODS: Information about all individual radiotherapy treatment was collected for two weeks from the Phoenix unit in our department. This information included diagnosis, treatment site, treatment time, fields per fraction, technique, use of blocks and wedges. Data were collected for two weeks (10 working days) in January 2008. During this time, 45 patients were treated with 450 fractions of external beam radiotherapy in Phoenix unit. RESULTS: The mean fraction duration, irradiation time and setup time were 9.55 minutes, 1.84 minutes and 7.66 minutes respectively. A mathematical workload model was derived using the average fraction duration time, total irradiation time and setup time of different types of treatment. A simple software program (Workload Calculation Chart) was also constructed in Microsoft Excel using the derived algorithm. The model based software program was tested and applied for one year and found that it can be used effectively to describe workload of teletherapy unit. CONCLUSION: Proposed methodology for workload modeling of teletherapy unit and the workload calculation software is very effective to quantitatively plan/calculate the optimal workload which will satisfy both the patient care administrator and radiation therapy technologists.

Development of an electronic radiation oncology patient information management system.

The quality of patient care is critically influenced by the availability of accurate information and its efficient management. Radiation oncology consists of many information components, for example there may be information related to the patient (e.g., profile, disease site, stage, etc.), to people (radiation oncologists, radiological physicists, technologists, etc.), and to equipment (diagnostic, planning, treatment, etc.). These different data must be integrated. A comprehensive information management system is essential for efficient storage and retrieval of the enormous amounts of information. A radiation therapy patient information system (RTPIS) has been developed using open source software. PHP and JAVA script was used as the programming languages, MySQL as the database, and HTML and CSF as the design tool. This system utilizes typical web browsing technology using a WAMP5 server. Any user having a unique user ID and password can access this RTPIS. The user ID and password is issued separately to each individual according to the person's job responsibilities and accountability, so that users will be able to only access data that is related to their job responsibilities. With this system authentic users will be able to use a simple web browsing procedure to gain instant access. All types of users in the radiation oncology department should find it user-friendly. The maintenance of the system will not require large human resources or space. The file storage and retrieval process would be be satisfactory, unique, uniform, and easily accessible with adequate data protection. There will be very little possibility of unauthorized handling with this system. There will also be minimal risk of loss or accidental destruction of information.