Clinical trial recommendations using Semantics-Based inductive inference and knowledge graph embeddings.

OBJECTIVE: Designing a new clinical trial entails many decisions, such as defining a cohort and setting the study objectives to name a few, and therefore can benefit from recommendations based on exhaustive mining of past clinical trial records. This study proposes an approach based on knowledge graph embeddings and semantics-driven inductive inference for generating such recommendations. METHOD: The proposed recommendation methodology is based on neural embeddings trained on first-of-its-kind knowledge graph constructed from clinical trials data. The methodology includes design of a knowledge graph for clinical trial data, evaluation of various knowledge graph embedding techniques for it, application of a novel inductive inference method using these embeddings, and generation of recommendations for clinical trial design. The study uses freely available data from clinicaltrials.gov and related sources. RESULTS: The proposed approach for recommendations obtained relevance scores ranging from 70% to 83%. These scores were determined by evaluating the text similarity of recommended elements to actual elements used in clinical trials that are in progress. Furthermore, the most pertinent recommendations were consistently located towards the top of the list, indicating the effectiveness of our method. CONCLUSION: Our study suggests that inductive inference using node semantics is a viable approach for generating recommendations using graphs neural embeddings, and that there is a potential for improvement in training graph embeddings using node semantics.

Patterns of Failure After Prostate-Only Radiotherapy in High-Risk Prostate Cancer: Implications for Refining Pelvic Nodal Contouring Guidelines.

PURPOSE: To study prostate specific membrane antigen - positron emission tomography (Ga68PSMA-PETCT) based patterns of relapse at biochemical failure (BCF) after prostate-only radiotherapy (PORT) in high-risk (HR) prostate cancer and its implications on pelvic contouring recommendations. METHODS AND MATERIALS: Patients with clinico-radiological high-risk node-negative prostate cancer treated with curative PORT and androgen deprivation therapy (ADT), either within the POP-RT randomised trial or off trial, who underwent a Ga68PSMA-PETCT upon BCF were included. Patterns of regional and distant recurrence on Ga68PSMA-PETCT were studied. Pelvic nodal recurrences were mapped with reference to the superior border of pubic symphysis. Pelvic lymph nodal caudal border (PLNcb) recommendations in the published contouring guidelines (RTOGcb, GETUGcb, PIVOTALcb, NRGcb, GFRUcb) were evaluated. RESULTS: Of the total 262 patients screened, 68 eligible patients were included (POP-RT trial 35 patients; off-trial 33 patients). Median follow-up was 91 months (IQR, 72-117) and median time to BCF was 65 months (IQR, 49-83). Regional and distant recurrence was seen in 31 (46%) and 31 (46%) patients, respectively. Of the nodal recurrences, nearly half (46%, 14/31) had no distant metastases and 64% (20/31) had a failure in the common iliac nodal region. The lower-most nodal recurrence was 20 mm cranial to the top of pubic symphysis (RTOGcb, GETUGcb, GFRUcb) and 10 mm cranial to the PIVOTALcb. The PLNcb recommended by NRG guideline (NRGcb) had an inter-patient variability of 32 mm, ranging from 16 mm above to 16 mm below the top of pubic symphysis, and the lower most nodal recurrence ranged from 4 mm to 36 mm cranial to NRGcb. CONCLUSION: Pelvic failures accounted for a major proportion of recurrences after prostate-only radiotherapy, with the caudal most nodal recurrence being 20 mm cranial to the top of pubic symphysis. This could have implications in defining the caudal border of contouring recommendations.

Reducing Salivary Toxicity with Adaptive Radiotherapy (ReSTART): A Randomized Controlled Trial Comparing Conventional IMRT to Adaptive IMRT in Head and Neck Squamous Cell Carcinomas.

BACKGROUND: The utility of Adaptive Radiotherapy (ART) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains to be ascertained. While multiple retrospective and single-arm prospective studies have demonstrated its efficacy in decreasing parotid doses and reducing xerostomia, adequate randomized evidence is lacking. METHODS AND ANALYSIS: ReSTART (Reducing Salivary Toxicity with Adaptive Radiotherapy) is an ongoing phase III randomized trial of patients with previously untreated, locally advanced HNSCC of the oropharynx, larynx, and hypopharynx. Patients are randomized in a 1:1 ratio to the standard Intensity Modulated Radiotherapy (IMRT) arm {Planning Target Volume (PTV) margin 5 mm} vs. Adaptive Radiotherapy arm (standard IMRT with a PTV margin 3 mm, two planned adaptive planning at 10th and 20th fractions). The stratification factors include the primary site and nodal stage. The RT dose prescribed is 66Gy in 30 fractions for high-risk PTV and 54Gy in 30 fractions for low-risk PTV over six weeks, along with concurrent chemotherapy. The primary endpoint is to compare salivary toxicity between arms using salivary scintigraphy 12 months' post-radiation. To detect a 25% improvement in the primary endpoint at 12 months in the ART arm with a two-sided 5% alpha value and a power of 80% (and 10% attrition ratio), a sample size of 130 patients is required (65 patients in each arm). The secondary endpoints include acute and late toxicities, locoregional control, disease-free survival, overall survival, quality of life, and xerostomia scores between the two arms. DISCUSSION: The ReSTART trial aims to answer an important question in Radiation Therapy for HNSCC, particularly in a resource-limited setting. The uniqueness of this trial, compared to other ongoing randomized trials, includes the PTV margins and the xerostomia assessment by scintigraphy at 12 months as the primary endpoint.

Synthesis, Spectral Characterization and Photoluminescence of 3-chloro-6-methoxy-2-(methylsulfanyl)quinoxaline in Different Solvents: An Experimental and Theoretical Investigation Using DFT.

In the present work, we synthesized 3-chloro-6-methoxy-2-(methyl sulfanyl) quinoxaline (3MSQ) using a microwave-assisted synthesis method. The physicochemical structural analysis of the synthesized compound utilizing 1H-NMR, 13C-NMR, and FT-IR spectroscopy techniques. The photophysical properties of 3MSQ was examined through absorption and fluorescence spectroscopy. Spectroscopic analyses revealed a bathochromic shift in both absorption and fluorescence spectra, attributed to the π → π* transition. Ground and excited state dipole moments was experimentally determined using the solvatochromic shift method, employing various correlations such as Lippert's, Bakhshiev's, Kawski-Chamma-Viallet's equations, and solvent polarity parameters. Our findings indicate that the excited state dipole moments exceed those of the ground state, suggesting increased polarity in the excited state. Further, the while detailed bond length, bond angles, dihedral angles, Mulliken charge distribution, ground state dipole moments and HOMO-LUMO energy gap estimated through ab initio computations using Gaussian-09W. The value of energy band gap obtained from both the methods are in good agreement. Furthermore, employing DFT computational analysis, we identified reactive centers such as electrophilic and nucleophilic sites using molecular electrostatic potential (MESP) 3D plots. Additionally, CIE chromaticity analysis was performed to understand the photoluminescent properties of 3MSQ. The insights derived from these analyses contribute to a better understanding of the molecule's electronic structure, photophysical properties, and solute-solvent interactions, thus providing valuable information regarding its behaviour and characteristics under diverse conditions. These results contribute to a comprehensive understanding of the molecular structure and properties of 3-chloro-6-methoxy-2-(methyl sulfanyl) quinoxaline (3MSQ).

Contralateral Nodal Relapse in Well-lateralised Oral Cavity Cancers Treated Uniformly with Ipsilateral Surgery and Adjuvant Radiotherapy With or Without Concurrent Chemotherapy: a Retrospective Study.

AIMS: To evaluate the incidence and pattern of contralateral nodal relapse (CLNR), contralateral nodal relapse-free survival (CLNRFS) and risk factors predicting CLNR in well-lateralised oral cavity cancers (OCC) treated with unilateral surgery and adjuvant ipsilateral radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Consecutive patients of well-lateralised OCC treated between 2012 and 2017 were included. The primary endpoint was incidence of CLNR and CLNRFS. Univariable and multivariable analyses were carried out to identify potential factors predicting CLNR. RESULTS: Of the 208 eligible patients, 21 (10%) developed isolated CLNR at a median follow-up of 45 months. The incidence of CLNR was 21.3% in node-positive patients. CLNR was most common at level IB (61.9%) followed by level II. The 5-year CLNRFS and overall survival were 82.5% and 57.7%, respectively. Any positive ipsilateral lymph node (P = 0.001), two or more positive lymph nodes (P < 0.001), involvement of ipsilateral level IB (P = 0.002) or level II lymph node (P < 0.001), presence of extranodal extension (P < 0.001), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.021) were significant factors for CLNR on univariable analysis. The presence of two or more positive lymph nodes (P < 0.001) was an independent prognostic factor for CLNR on multivariable analysis. CLNR increased significantly with each increasing lymph node number beyond two compared with node-negative patients. CONCLUSION: The overall incidence of isolated CLNR is low in well-lateralised OCC. Patients with two or more positive lymph nodes have a higher risk of CLNR and may be considered for elective treatment of contralateral neck.

Detection of Circulating Tumor Cells by Cell Block Technique in Malignant Tumors.

Introduction: Cancer is a leading cause of death worldwide and is a major cause of morbidity. To deal with this magnitude of cancers and their diagnostic and prognostics, a multitude of prognostic biomarkers for various cancers have been explored over the decades, with detection of circulating tumor cells (CTCs) in the peripheral blood being one of them. This study was undertaken to explore the routine procedure of cell block in the cytopathology lab to isolate and detect CTCs. Materials and Methods: In this cross-sectional study, 112 peripheral blood samples sent for routine blood investigations of various cancer patients were utilized for the preparation of cell block. The sections from the cell block were stained routinely and evaluated for the presence of CTCs. The statistical analysis was done using Mac Statplus software version 8.0. Results: The malignancies were tabulated as per the International Classification of Diseases for Oncology, third edition (ICD-O-3). The maximum number of cases were from C 50 (breast) - 41/112 (36.6%), followed by C15-C26 (Digestive organs) - 19/112 (16.9%), and C00-C14 (lip, oral cavity, and pharynx) - 18/112 (16.07%) cases. CTC was detected in six (5.35%) out of 112 cases, out of which three were from the breast and one each from category C6.9 (mouth), C32.0 (glottis), and C53.8 (cervix uteri). Conclusion: Among various advanced and molecular techniques available for the detection of CTCs, the cell block technique proves to be one of the effective methods, especially in resource-limited settings as these can further be utilized for additional diagnostic techniques similar to the ones employed for routine paraffin blocks.

Correlative Evaluation of Seven Cytological 3-Tier Grading Systems of Breast Carcinoma with the Standard Histological Grading: A 4 and ½ Year Study.

INTRODUCTION: The early diagnosis of breast carcinoma is of paramount importance in its management. Fine-needle aspiration cytology (FNAC) has the potential to play a pivotal role in providing the relevant information on the aggressiveness of this tumor. But there is no gold standard when it comes to cytological grading of breast carcinoma as there is no consensus between the pathologists and also the clinicians as to which grading is as par with the gold standard Elston-Ellis modification of Scarff-Bloom-Richardson (SBR) histological grading. This study was undertaken to study seven cytological 3-tier grading systems, namely, Robinson's, Fisher's, Mouriquand's, Dabbs', Khan's, Taniguchi's, and Howells's and to correlate them with the Elston-Ellis modification of SBR histological grading system so as to determine the finest cytological grading system which could be reliably used in our routine practice. MATERIAL AND METHODS: A total of 117 breast carcinoma cases diagnosed on FNAC were graded using seven 3-tier cytological grading systems and were correlated with Elston-Ellis modification of SBR histological grading system. Concordance, kappa measurement, and various correlation studies were done using SPSS software version 2021. RESULTS: Robinson's method showed a better concordance (84.61%), a better correlation (Spearman = 0.750, τ = 0.731, p < 0.001), and a substantial kappa value of agreement (κ = 0.701) with SBR grading system compared to other system closely followed by Fisher's system. CONCLUSIONS: Even though all the seven 3-tier cytological grading systems positively correlated with the SBR histologic grading of breast carcinoma, Robinson's method showed better concordance and correlation with a substantial kappa value of agreement in comparison to other 3-tier cytology grading systems. Hence, Robinson's grading which is simpler and also feasible should be incorporated in the routine cytology reporting of breast carcinoma.

Study Protocol of the Bladder Adjuvant RadioTherapy (BART) Trial: A Randomised Phase III Trial of Adjuvant Radiotherapy Following Cystectomy in Bladder Cancer.

AIMS: To assess the efficacy and safety of adjuvant radiotherapy in patients with high-risk muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC) and chemotherapy. MATERIALS AND METHODS: The BART (Bladder Adjuvant RadioTherapy) trial is an ongoing multicentric, randomised, phase III trial comparing the efficacy and safety of adjuvant radiotherapy versus observation in patients with high-risk MIBC. The key eligibility criteria include ≥pT3, node-positive (pN+), positive margins and/or nodal yield <10, or, neoadjuvant chemotherapy for cT3/T4/N+ disease. In total, 153 patients will be accrued and randomised, in a 1:1 ratio, to either observation (standard arm) or adjuvant radiotherapy (test arm) following surgery and chemotherapy. Stratification parameters include nodal status (N+ versus N0) and chemotherapy (neoadjuvant chemotherapy versus adjuvant chemotherapy versus no chemotherapy). For patients in the test arm, adjuvant radiotherapy to cystectomy bed and pelvic nodes is planned with intensity-modulated radiotherapy to a dose of 50.4 Gy in 28 fractions using daily image guidance. All patients will follow-up with 3-monthly clinical review and urine cytology for 2 years and subsequently 6 monthly until 5 years, with contrast-enhanced computed tomography abdomen pelvis 6 monthly for 2 years and annually until 5 years. Physician-scored toxicity using Common Terminology Criteria for Adverse Events version 5.0 and patient-reported quality of life using the Functional Assessment of Cancer Therapy - Colorectal questionnaire is recorded pre-treatment and at follow-up. ENDPOINTS AND STATISTICS: The primary endpoint is 2-year locoregional recurrence-free survival. The sample size calculation was based on the estimated improvement in 2-year locoregional recurrence-free survival from 70% in the standard arm to 85% in the test arm (hazard ratio 0.45) using 80% statistical power and a two-sided alpha error of 0.05. Secondary endpoints include disease-free survival, overall survival, acute and late toxicity, patterns of failure and quality of life. CONCLUSION: The BART trial aims to evaluate whether contemporary radiotherapy after standard-of-care surgery and chemotherapy reduces pelvic recurrences safely and also potentially affects survival in high-risk MIBC.

Multi-Institutional Clinical Outcomes of Biopsy Gleason Grade Group 5 Prostate Cancers Treated With Contemporary High-Dose Radiation and Long-Term Androgen Deprivation Therapy.

AIMS: This multicentric retrospective study reports long-term clinical outcomes of non-metastatic grade group 5 prostate cancers treated with external beam radiotherapy (EBRT) alone with long-term androgen deprivation therapy (ADT). MATERIALS AND METHODS: Patients treated across 19 institutions were studied. The key endpoints that were evaluated were 5-year biochemical recurrence-free survival (bRFS), metastases-free survival (MFS), overall survival, together with EBRT-related acute and late toxicities. The impact of various prognostic factors on the studied endpoints was analysed using univariate and multivariate analyses. RESULTS: Among the 462 patients, 88% (405) had Gleason 9 disease and 31% (142) had primary Gleason pattern 5. A prostate-specific membrane antigen positron emission tomography-computed tomography scan was used for staging in 33% (153), 80% (371) were staged as T3/T4 and 30% (142) with pelvic nodal disease. The median ADT duration was 24 months; 66% received hypofractionated EBRT and 71.4% (330) received pelvic nodal irradiation. With a median follow-up of 56 months, the 5-year bRFS, MFS and overall survival were 73.1%, 77.4% and 90.5%, respectively. Primary Gleason pattern 5 was associated with worse bRFS, MFS and overall survival with hazard ratios of 0.51 (95% confidence interval 0.35 to 0.73, P < 0.001), 0.64 (95% confidence interval 0.43 to 0.96, P = 0.031) and 0.52 (95% confidence interval 0.28 to 0.97, P = 0.040), respectively, whereas pelvic nodal disease was associated with worse bRFS (hazard ratio 0.67, 95% confidence interval 0.46 to 0.98, P = 0.039) and MFS (hazard ratio 0.56, 95% confidence interval 0.37 to 0.85, P = 0.006). The acute and late radiation-related toxicities were low overall and pelvic nodal irradiation was associated with higher toxicities. CONCLUSION: Contemporary EBRT and long-term ADT led to excellent 5-year clinical outcomes and low rates of toxicity in this cohort of non-metastatic grade group 5 prostate cancers. Primary Gleason pattern 5 and pelvic node disease portends inferior clinical outcomes.

Improving Quality of Life with Brachytherapy for Urological Malignancies.

Brachytherapy for localised prostate, muscle-invasive bladder and penile cancer is well established, providing high tumour dose delivery and minimising normal tissue doses compared with external beam techniques. In prostate cancer, the main impact on quality of life relates to diminished sexual function and irritative or obstructive urinary symptoms, which are seen up to 15 years after treatment. Significant changes in bowel function are rare. Compared with radical prostatectomy or external beam radiotherapy, irritative or obstructive urinary symptoms are more prominent, whereas incontinence is less than after radical prostatectomy and bowel changes are less than after external beam radiotherapy. For muscle-invasive bladder cancer, when compared with radical cystectomy, although no difference is seen for urinary symptoms or fatigue, role and social functioning scores are higher and there is better post-treatment sexual function in both men and women. Compared with surgical treatment for penile cancer, brachytherapy results in better erectile function scores than after glansectomy and partial penectomy and high quality of life scores, with good satisfaction ratings for cosmetic appearance.

Posterior superior alveolar nerve block alone in the extraction of upper third molars: a prospective clinical study

Background@#Third molar extraction is the most commonly performed minor oral surgical procedure in outpatient settings and requires regional anesthesia for pain control. Extraction of the maxillary molars commonly requires both posterior superior alveolar nerve block (PSANB) and greater palatine nerve block (GPNB), depending on the nerve innervations of the subject teeth. We aimed to study the effectiveness of PSANB alone in maxillary third molar (MTM) extraction. @*Methods@#A sample size comprising 100 erupted and semi-erupted MTM was selected and subjected to study for extraction. Under strict aseptic conditions, the patients were subjected to the classical local anesthesia technique of PSANB alone with 2% lignocaine hydrochloride and adrenaline 1:80,000. After a latency period of 10 min, objective assessment of the buccal and palatal mucosa was performed. A numerical rating scale and visual analog scale were used. @*Results@#In the post-latency period of 10 min, the depth of anesthesia obtained in our sample on the buccal side extended from the maxillary tuberosity posteriorly to the mesial of the first premolar (15%), second premolar (41%), and first molar (44%). This inferred that anesthesia was effectively high until the first molars and was less effective further anteriorly due to nerve innervation. The depth of anesthesia on the palatal aspect was up to the first molar (33%), second molar (67%), and lateromedially; 6% of the patients received anesthesia only to the alveolar region, whereas 66% received up to 1.5 cm to the mid-palatal raphe. In 5% of the cases, regional anesthesia was re-administered. An additional 1.8 ml PSANB was required in four patients, and another patient was administered a GPNB in addition to the PSANB during the time of extraction and elevation. @*Conclusion@#The results of our study emphasize that PSANB alone is sufficient for the extraction of MTM in most cases, thereby obviating the need for poorly tolerated palatal injections.

Synthesis of nano hydroxyapatite from Hypopthalmichthys molitrix (silver carp) bone waste by two different methods: a comparative biophysical and in vitro evaluation on osteoblast MG63 cell lines.

More than a thousand tonnes of fish bone wastes can be transformed into biomedical products annually. Alkaline hydrolysis and thermal calcification were used to create nanosized hydroxyapatite (HAp) crystals from Silver carp bone wastes. Biophysical tests were used to determine the nano size and chemical composition of synthesised hydroxyapatite. Alkaline hydrolysis hydroxyapatite (AH-HAp) was 58.3 nm, while Thermal calcination hydroxyapatite (TC-HAp) was 64.3 nm in size, confirmed by Atomic Force Microscopy. Energy Dispersive X-ray Analysis studies showed Ca/P (Calcium phosphate) ratio of AH-HAp to be 1.65, whereas TC-HAp as 1.45, confirming AH-HAp to be organically rich along with a similar Ca/P ratio as natural HAp. Fourier Transform Infrared Spectroscopy spectra indicated HAp formation from both procedures, however AH-HAp had superior crystallinity than TC-HAp confirmed from X-Ray Diffraction spectra. MG63 osteoblast cell lines showed 91% cell viability in cytotoxicity studies and 70.1% proliferation efficiency in Alkaline Phosphatase assay, which was higher than TC-HAp. The present study shows that HAp produced via alkaline hydrolysis has better biocompatibility which enhances its applicability as a biomaterial, than HAp synthesized through thermal calcination, which tends to incinerate organic moieties.

A comparative assessment of collagen type 1 from silver carp (fresh water) and milk shark(marine) fish waste.

In this study, a comparative structural and bioactive analysis of collagen extracted from the skin of bony and cartilaginous fishes. The acid-soluble method was followed to extract the collagen from Hypophthalmichthys molitrix (silver carp) and Rhizoprionodon acutus (milk shark) followed by purification using Ion exchange chromatography. A higher yield of collagen was obtained from the skin of SCsk (69.45%) as compared to SHsk (55.29%). SDS PAGE displayed the characteristic α, ß bands of the collagen type1. The native conformation and secondary structure stability of collagen were confirmed by FTIR, XRD and CD studies. The SEM micrographs exhibited the layered and fibrillar nature of the collagen from SHsk and SCsk, respectively. Relative solubility and thermal denaturation analysis showed SCsk to be more stable, but SHsk could withstand higher temperatures. 53.65% of antioxidant activity was observed in SCsk collagen as compared to SHsk (45.9%). Haemocompatibility, cell viability and adhesion results also displayed silvercarp skin to be a better source than Shark skin collagen. The results establish the potential of silver carp collagen as a biomaterial that can have many commercial applications in tissue engineering, cosmetics and food industries.

Impact of Adjuvant Treatment in pN3 Penile Cancer.

AIMS: Due to the lack of high-quality evidence and consensus on adjuvant treatment for locoregionally advanced penile cancer, we reviewed the outcomes of pN3 patients to determine the suitable adjuvant treatment options. PATIENTS AND METHODS: All consecutive pN3 penile cancer patients treated at our institution between January 2010 and December 2018 were reviewed to assess the impact of demographical, pathological and treatment factors on disease-free survival (DFS) and overall survival. The DFS and overall survival were estimated using the Kaplan-Meier method and association was tested using the Cox regression model (two-sided test with P < 0.05 considered significant). RESULTS: Of 128 patients, 31 (24%) had pelvic nodal involvement. Twenty-six patients (20.3%) received no adjuvant treatment, 40 (31.3%) received single modality adjuvant treatment and 62 (48.4%) received multimodality adjuvant treatment (a combination of chemotherapy and radiotherapy). At a median follow-up of 22 months, the DFS and overall survival were 55.4 and 62%, respectively. The best DFS and overall survival was noted with chemotherapy followed by concurrent chemoradiation (C-CTRT; 93% each). On multivariate analysis, both DFS and overall survival were worse with pelvic node involvement (2.2 [1.3-4], P = 0.027 and 2.2 [1.3-4], P = 0.027, respectively) and better with any adjuvant treatment (single modality: 3 [1.5-5.5], P < 0.001; multimodality: 3.1 [1.6-6], P < 0.001). C-CTRT was associated with improved DFS over chemotherapy alone (0.17 [0.4-0.78], P = 0.02) but not over radiotherapy alone (0.35 [0.07-1.6], P = 0.19). In patients with no pelvic nodes involved, chemotherapy and radiotherapy as single modalities were associated with similar DFS and overall survival. In patients with pelvic nodes, multimodality treatment was associated with better DFS than single modality treatment (0.3 [0.1-1], P = 0.05). CONCLUSION: pN3 penile cancer is a diverse prognostic group with poorer outcomes associated with pelvic nodes. Single modality adjuvant treatment may be adequate in inguinal nodes with extranodal extension, but multimodality treatment should be given in patients with pelvic nodal involvement.

Post-cricoid and Upper Oesophagus Cancers Treated with Organ Preservation Using Intensity-modulated Image-guided Radiotherapy: a Phase II Prospective Study of Outcomes, Toxicity and Quality of Life.

AIMS: To prospectively examine the outcomes, toxicity and quality of life (QoL) of patients with post-cricoid and upper oesophagus (PCUE) cancers treated with an organ-preservation approach of (chemo)-radiotherapy using intensity-modulated image-guided radiotherapy (IM-IGRT). MATERIALS AND METHODS: This phase II prospective study was conducted at a tertiary cancer centre from February 2017 to January 2020. Forty patients with squamous cell carcinoma of PCUE of stage T1-3, N0-2, M0 were accrued. Gross exolaryngeal extension/dysfunctional larynx were major exclusion criteria. Patients received 63-66 Gy in once-daily fractions using volumetric modulated arc therapy with daily IGRT. Outcome measures included disease-related outcomes, patterns of failure, Radiation Therapy Oncology Group toxicities, feeding tube dependency and QoL. RESULTS: The median follow-up was 22 months. Twenty-six (87.5%) patients had locoregionally advanced disease and 34 (85%) patients received (chemo)-radiotherapy. A complete response was observed in 26 (65%) patients. The 2-year locoregional control, event-free survival and cause-specific survival were 59.6%, 40.2% and 44.8%, respectively. The volume of primary tumour (GTVPvol) exceeding 28 cm3 had inferior overall survival (P = 0.005) on univariate analysis. Multivariable analysis showed GTVPvol and positron emission tomography-computed tomography maximum standardised uptake value to be independently predictive for event-free and overall survival. A feeding tube requirement at presentation was seen in 11 (27.5%) patients, whereas long-term feeding tube dependency at 6 months was seen in 10 (37%) patients. For QoL, a statistical improvement in pain, appetite loss and swallowing was observed over time. CONCLUSION: Although the outcomes of PCUE cancers remain dismal, the use of state of the art diagnostic modalities, careful case selection and modern radiotherapy techniques improved outcomes as compared with before in this exclusive analysis of PCUE cancers.

Isolated skyrmion, skyrmion lattice and antiskyrmion lattice creation through magnetization reversal in Co/Pd nanostructure.

Skyrmion and antiskyrmion spin textures are axisymmetric inhomogeneous localized objects with distinct chirality in magnetic systems. These spin textures are potential candidates for the next generation energy-efficient spintronic applications due to their unique topological properties. Controlled and effective creation of the spin textures is required to use in conventional and neuromorphic computing applications. Here we show by micromagnetic simulations creating an isolated skyrmion, skyrmion lattice and antiskyrmion lattice through the magnetization reversal in Co/Pd multilayer nanostructure using spin-polarized current. The spin textures' stability depends on the spin-polarized current density, current pulse width, and Dzyaloshinskii-Moriya interaction (DMI). Antiskyrmions are evolved during the formation of a single skyrmion and skyrmion lattice. Skyrmion and antiskyrmion lattices together are observed for lower pulse width, 0.05 ns. Our micromagnetic studies suggest that the two distinct lattice phases' evolution could help to design the topological spin textures-based devices.

A practical approach to bladder preservation with hypofractionated radiotherapy for localised muscle-invasive bladder cancer.

Bladder preservation with trimodality treatment (TMT) is an alternative strategy to radical cystectomy (RC) for the management of localised muscle invasive bladder cancer (MIBC). TMT comprises of transurethral resection of the bladder tumour (TURBT) followed by radiotherapy with concurrent radiosensitisation. TMT studies have shown neo-adjuvant chemotherapy with cisplatin-based regimens is often given to further improve survival outcomes. A hypofractionated radiotherapy regimen is preferable due to its non-inferiority in local control and late toxicities. Radiosensitisation can comprise concurrent chemotherapy (with gemcitabine, cisplatin or combination fluorouracil and mitomycin), CON (carbogen and nicotinomide) or hyperthermic treatment. Radiotherapy techniques are continuously improving and becoming more personalised. As the bladder is a mobile structure subject to volumetric changes from filling, an adaptive approach can optimise bladder coverage and reduce dose to normal tissue. Adaptive radiotherapy (ART) is an evolving field that aims to overcome this. Improved knowledge of tumour biology and advances in imaging techniques aims to further optimise and personalise treatment.

Cold abscess of dental origin in a 7-year-old child.

Abscess related to an infected tooth is mostly associated with pyogenic infection, but sometimes, it can be asymptomatic and indicate a chronic condition. This case report shows cold abscess with a draining sinus due to dental origin. A 7-year-old female patient complained of pain with respect to grossly decayed tooth and recurrent swelling with no response to medications. After investigations and management of the lesion, it was concluded as abscess due to chronic granulomatous infection. Cold abscess is a classical manifestation of tuberculosis with no signs of inflammation. More than 60% of cases of this pathology occur in patients below 15 years old. It needs various clinical, histopathological, and laboratory investigations. Although rare, it should be considered as a differential diagnosis when no improvement occurs postroutine therapy to prevent serious complications. Furthermore, various precautions should be taken by the clinicians to prevent cross-infection.

Adjuvant and Neoadjuvant Radiation Therapy for Locally Advanced Bladder Cancer.

Local-regional failure for patients with ≥pT3 urothelial carcinoma after radical cystectomy is a significant clinical challenge. Prospective randomised trials have failed to show that chemotherapy reduces the risk of local-regional recurrences. Salvage treatment for local failures is difficult and often unsuccessful. There is promising evidence, particularly from a recent Egyptian National Cancer Institute trial, that radiation therapy plus chemotherapy can significantly reduce local recurrences compared with chemotherapy alone, and that this improvement in local-regional control may translate to meaningful improvements in disease-free and overall survival with acceptable toxicity. In light of the high rates of local failure following cystectomy for locally advanced disease and the progress that has been made in identifying patients at high risk of failure and the patterns of failure in the pelvis, the National Comprehensive Cancer Network guidelines were revised to include postoperative radiotherapy as an option to consider for patients with ≥pT3 disease. Here we review the problem of local-regional failure after cystectomy, identify patients who would probably benefit from adjuvant radiotherapy, review the patterns of pelvic failure after cystectomy, discuss technical details of radiation treatment and review the modern literature on this topic. Adjuvant radiotherapy should be considered as a treatment option for patients with locally advanced disease, especially those with positive margins or squamous cell carcinoma.