Weibull parametric model for survival analysis in women with endometrial cancer using clinical and T2-weighted MRI radiomic features.

BACKGROUND: Semiparametric survival analysis such as the Cox proportional hazards (CPH) regression model is commonly employed in endometrial cancer (EC) study. Although this method does not need to know the baseline hazard function, it cannot estimate event time ratio (ETR) which measures relative increase or decrease in survival time. To estimate ETR, the Weibull parametric model needs to be applied. The objective of this study is to develop and evaluate the Weibull parametric model for EC patients' survival analysis. METHODS: Training (n = 411) and testing (n = 80) datasets from EC patients were retrospectively collected to investigate this problem. To determine the optimal CPH model from the training dataset, a bi-level model selection with minimax concave penalty was applied to select clinical and radiomic features which were obtained from T2-weighted MRI images. After the CPH model was built, model diagnostic was carried out to evaluate the proportional hazard assumption with Schoenfeld test. Survival data were fitted into a Weibull model and hazard ratio (HR) and ETR were calculated from the model. Brier score and time-dependent area under the receiver operating characteristic curve (AUC) were compared between CPH and Weibull models. Goodness of the fit was measured with Kolmogorov-Smirnov (KS) statistic. RESULTS: Although the proportional hazard assumption holds for fitting EC survival data, the linearity of the model assumption is suspicious as there are trends in the age and cancer grade predictors. The result also showed that there was a significant relation between the EC survival data and the Weibull distribution. Finally, it showed that Weibull model has a larger AUC value than CPH model in general, and it also has smaller Brier score value for EC survival prediction using both training and testing datasets, suggesting that it is more accurate to use the Weibull model for EC survival analysis. CONCLUSIONS: The Weibull parametric model for EC survival analysis allows simultaneous characterization of the treatment effect in terms of the hazard ratio and the event time ratio (ETR), which is likely to be better understood. This method can be extended to study progression free survival and disease specific survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT03543215, https://clinicaltrials.gov/ , date of registration: 30th June 2017.

The Hammersmith Score optimises patient selection and predicts for overall survival in early-phase cancer trial participants independent of tumour burden.

INTRODUCTION: As tumour response rates are increasingly demonstrated in early-phase cancer trials (EPCT), optimal patient selection and accurate prognostication is paramount. Hammersmith Score (HS), a simple prognostic index derived on routine biochemical measures (Albumin <35g/L, Lactate Dehydrogenase (LDH) >450 IU/L, Sodium <135mmol/L) is a validated predictor of response and survival in EPCT participants. HS has not been validated in the cancer immunotherapy era. METHODS: We retrospectively analysed characteristics and outcomes of unselected referrals to our early-phase unit (12/2019-12/2022). Independent predictors for overall survival (OS) were identified from univariable and multivariable models. HS was calculated for 66 eligible trial participants and compared with the Royal Marsden Score (RMS) to predict OS. Multivariable logistic regression and c-index was used to compare predictive ability of prognostic models. RESULTS: Of 212 referrals, 147 patients were screened and 82 patients treated in EPCT. Prognostic stratification by HS identifies significant difference in median OS and HS was confirmed as a multivariable predictor for OS (HR: HS 1 vs. 0 2.51, 95%CI: 1.01-6.24, p=0.049; HS 2/3 vs. 0: 10.32, 95%CI: 2.15-49.62, p=0.004; C-index 0.771) with superior multivariable predictive ability than RMS (HR: RMS 2 vs. 0/1 5.46, 95%CI: 1.12-26.57, p=0.036; RMS 3 vs. 0/1 6.83, 95%CI: 1.15-40.53, p<0.001; C-index 0.743). CONCLUSIONS: HS is a validated prognostic index for patients with advanced cancer treated in the context of modern EPCTs, independent of tumour burden. HS is a simple, inexpensive prognostic tool to optimise referral for EPCT.

Prediction of Deep Myometrial Infiltration, Clinical Risk Category, Histological Type, and Lymphovascular Space Invasion in Women with Endometrial Cancer Based on Clinical and T2-Weighted MRI Radiomic Features.

PURPOSE: To predict deep myometrial infiltration (DMI), clinical risk category, histological type, and lymphovascular space invasion (LVSI) in women with endometrial cancer using machine learning classification methods based on clinical and image signatures from T2-weighted MR images. METHODS: A training dataset containing 413 patients and an independent testing dataset consisting of 82 cases were employed in this retrospective study. Manual segmentation of the whole tumor volume on sagittal T2-weighted MRI was performed. Clinical and radiomic features were extracted to predict: (i) DMI of endometrial cancer patients, (ii) endometrial cancer clinical high-risk level, (iii) histological subtype of tumor, and (iv) presence of LVSI. A classification model with different automatically selected hyperparameter values was created. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, F1 score, average recall, and average precision were calculated to evaluate different models. RESULTS: Based on the independent external testing dataset, the AUCs for DMI, high-risk endometrial cancer, endometrial histological type, and LVSI classification were 0.79, 0.82, 0.91, and 0.85, respectively. The corresponding 95% confidence intervals (CI) of the AUCs were [0.69, 0.89], [0.75, 0.91], [0.83, 0.97], and [0.77, 0.93], respectively. CONCLUSION: It is possible to classify endometrial cancer DMI, risk, histology type, and LVSI using different machine learning methods.

Personalized Prehabilitation Improves Tolerance to Chemotherapy in Patients with Oesophageal Cancer.

BACKGROUND: Prehabilitation programmes aim to optimise patients before and after cancer treatment including surgery. Previous studies in surgical patients demonstrate that prehabilitation improves pre-operative fitness and overcomes the negative impact of neoadjuvant chemotherapy on fitness. The aim of this study was to assess the impact of prehabilitation on the tolerance of neoadjuvant chemotherapy in patients with oesophageal cancer. METHODS: Patients with oesophageal or gastroesophageal junction (GOJ) cancer from two oncology centres were retrospectively included in the present comparative cohort study; one provided a multimodal prehabilitation programme and one did not offer any prehabilitation. Tolerance of chemotherapy, defined as completion of the full chemotherapy regime as per protocol, was compared between the two groups. RESULTS: In terms of participants, 92 patients were included in this study, 47 patients in the prehabilitation cohort and 45 in the control cohort. Compared with the control group, the prehabilitation group demonstrated an improved rate of chemotherapy completion (p = 0.029). In multivariate analysis, participation in prehabilitation was significantly associated with an improved rate of chemotherapy completion. CONCLUSION: The findings of this exploratory study suggest that prehabilitation is associated with better tolerance for chemotherapy. Further research is needed to establish the long-term impact of prehabilitation on oncological outcomes.

An Integrated Clinical-MR Radiomics Model to Estimate Survival Time in Patients With Endometrial Cancer.

BACKGROUND: Determination of survival time in women with endometrial cancer using clinical features remains imprecise. Features from MRI may improve the survival estimation allowing improved treatment planning. PURPOSE: To identify clinical features and imaging signatures on T2-weighted MRI that can be used in an integrated model to estimate survival time for endometrial cancer subjects. STUDY TYPE: Retrospective. POPULATION: Four hundred thirteen patients with endometrial cancer as training (N = 330, 66.41 ± 11.42 years) and validation (N = 83, 67.60 ± 11.89 years) data and an independent set of 82 subjects as testing data (63.26 ± 12.38 years). FIELD STRENGTH/SEQUENCE: 1.5-T and 3-T scanners with sagittal T2-weighted spin echo sequence. ASSESSMENT: Tumor regions were manually segmented on T2-weighted images. Features were extracted from segmented masks, and clinical variables including age, cancer histologic grade and risk score were included in a Cox proportional hazards (CPH) model. A group least absolute shrinkage and selection operator method was implemented to determine the model from the training and validation datasets. STATISTICAL TESTS: A likelihood-ratio test and decision curve analysis were applied to compare the models. Concordance index (CI) and area under the receiver operating characteristic curves (AUCs) were calculated to assess the model. RESULTS: Three radiomic features (two image intensity and volume features) and two clinical variables (age and cancer grade) were selected as predictors in the integrated model. The CI was 0.797 for the clinical model (includes clinical variables only) and 0.818 for the integrated model using training and validation datasets, the associated mean AUC value was 0.805 and 0.853. Using the testing dataset, the CI was 0.792 and 0.882, significantly different and the mean AUC was 0.624 and 0.727 for the clinical model and integrated model, respectively. DATA CONCLUSION: The proposed CPH model with radiomic signatures may serve as a tool to improve estimated survival time in women with endometrial cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Silk Fibroin/Tannin/ZnO Nanocomposite Hydrogel with Hemostatic Activities.

The inevitable bleeding and infections caused by disasters and accidents are the main causes of death owing to extrinsic trauma. Hemostatic agents are often used to quickly suppress bleeding and infection, and they can solve this problem in a short time. Silk fibroin (SF) has poor processibility in water, owing to incomplete solubility therein. In this study, aiming to overcome this disadvantage, a modified silk fibroin (SF-BGE), easily soluble in water, was prepared by introducing butyl glycidyl ether (BGE) into its side chain. Subsequently, a small amount of tannic acid (TA) was introduced to prepare an SF-BGE /TA solution, and ZnO nanoparticles (NPs) were added to the solution to form the coordination bonds between the ZnO and TA, leading to an SF-based nanocomposite hydrogel. A structural characterization of the SF-BGE, SF-BGE/TA, SF-BGE/TA/ZnO, and the coordination bonds between ZnO/TA was observed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and the phase change was observed by rheological measurements. The pore formation of the SF-BGE/TA/ZnO hydrogel and dispersibility of ZnO were verified through energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM). The cytocompatible and hemostatic performances of the SF-BGE/TA/ZnO NPs composite hydrogels were evaluated, and the hydrogels showed superior hemostatic and cytocompatible activities. Therefore, the SF-based nanocomposite hydrogel is considered as a promising material for hemostasis.

Optimal method for metabolic tumour volume assessment of cervical cancers with inter-observer agreement on [18F]-fluoro-deoxy-glucose positron emission tomography with computed tomography.

PURPOSE: Cervical cancer metabolic tumour volume (MTV) derived from [18F]-FDG PET/CT has a role in prognostication and therapy planning. There is no standard method of outlining MTV on [18F]-FDG PET/CT. The aim of this study was to assess the optimal method to outline primary cervical tumours on [18F]-FDG PET/CT using MRI-derived tumour volumes as the reference standard. METHODS: 81 consecutive cervical cancer patients with pre-treatment staging MRI and [18F]-FDG PET/CT imaging were included. MRI volumes were compared with different PET segmentation methods. Method 1 measured MTVs at different SUVmax thresholds ranging from 20 to 60% (MTV20-MTV60) with bladder masking and manual adjustment when required. Method 2 created an isocontour around the tumour prior to different SUVmax thresholds being applied. Method 3 used an automated gradient method. Inter-observer agreement of MTV, following manual adjustment when required, was recorded. RESULTS: For method 1, the MTV25 and MTV30 were closest to the MRI volumes for both readers (mean percentage change from MRI volume of 2.9% and 13.4% for MTV25 and - 13.1% and - 2.0% for MTV30 for readers 1 and 2). 70% of lesions required manual adjustment at MTV25 compared with 45% at MTV30. There was excellent inter-observer agreement between MTV30 to MTV60 (ICC ranged from 0.898-0.976 with narrow 95% confidence intervals (CIs)) and moderate agreement at lower thresholds (ICC estimates of 0.534 and 0.617, respectively for the MTV20 and MTV25 with wide 95% CIs). Bladder masking was performed in 86% of cases overall. For method 2, excellent correlation was demonstrated at MTV25 and MTV30 (mean % change from MRI volume of -3.9% and - 8.6% for MTV25 and - 16.9% and 19% for MTV30 for readers 1 and 2, respectively). This method also demonstrated excellent ICC across all thresholds with no manual adjustment. Method 3 demonstrated excellent ICC of 0.96 (95% CI 0.94-0.97) but had a mean percentage difference from the MRI volume of - 19.1 and - 18.2% for readers 1 and 2, respectively. 21% required manual adjustment for both readers. CONCLUSION: MTV30 provides the optimal correlation with MRI volume taking into consideration the excellent inter-reader agreement and less requirement for manual adjustment.

Development and Utilization of a Rapid and Accurate Epidemic Investigation Support System for COVID-19.

OBJECTIVES: In this pandemic situation caused by a novel coronavirus disease in 2019 (COVID-19), an electronic support system that can rapidly and accurately perform epidemic investigations, is needed. It would systematically secure and analyze patients' data (who have been confirmed to have the infection), location information, and credit card usage. METHODS: The "Infectious Disease Prevention and Control Act" in South Korea, established a legal basis for the securement, handling procedure, and disclosure of information required for epidemic investigations. The Epidemic Investigation Support System (EISS) was developed as an application platform on the Smart City data platform. RESULTS: The EISS performed the function of inter-institutional communication which reduced the processing period of patients' data in comparison to other methods. This system automatically marked confirmed cases' tracking data on a map and hot-spot analysis which lead to the prediction of areas where people may be vulnerable to infection. CONCLUSION: The EISS was designed and implemented for use during an epidemic investigation to prevent the spread of an infectious disease, by specifically tracking confirmed cases of infection.

FDG-PET Imaging in Cervical Cancer.

FDG-PET/CT has an established role in the initial staging of locally advanced cervical cancers, particularly in evaluation of nodal disease and distant metastases. It is common practice to perform FDG-PET/CT 3 months postcompletion of chemoradiotherapy as it can predict outcome and be used to tailor management, including adjuvant therapy and follow-up. It is also routinely used prior to pelvic exenterative surgery to ensure there is no disease outside the pelvis. There is growing evidence that FDG-PET-derived parameters are prognostic and could potentially be used to tailor therapy. This review outlines the use of FDG-PET/CT imaging in cervical cancer.

Surgery for Recurrent Uterine Cancer: Surgical Outcomes and Implications for Survival-A Case Series.

OBJECTIVE: The purpose of this study was to describe the patterns of relapse in uterine cancer (UC) and the role of surgery in the recurrent setting. METHODS: We describe surgical and clinical outcomes of all patients who underwent surgery for recurrent UC in a gynecological oncology tertiary referral center between May 1, 2013, and April 30, 2016. Progression-free survival and overall survival were estimated using Kaplan-Meier methods with the surgery at relapse being the starting point. RESULTS: We evaluated 15 patients with a median age of 66 years. The predominant histology was the endometrioid variant (n = 11; 73.3%). The median interval between the end of previous treatment and relapse surgery was 24 months (range, 8-164). Locoregional pelvic recurrences were the most common type of recurrence (n = 13; 86.7%) with the para-aortic lymph node space being the most commonly affected extrapelvic site (13%). Patients predominantly presented with a multifocal pattern of relapse (n = 10; 66.7%) requiring multivisceral resections such as bowel (n = 7; 46.6%) and/or bladder/ureteric resections (n = 8; 53.3%) to achieve complete tumor clearance. All patients were operated tumor free with a 30-day major morbidity and mortality rate of 6.7% and 0%, respectively. Five patients (33.3%) received postoperative chemotherapy or radiotherapy. Five patients (33.3%) relapsed, and 3 died within a mean follow-up of 12.4 months (95% confidence interval [CI], 6.5-18.2). Two of those patients had a sarcoma.Mean progression-free survival and overall survival for the entire cohort postrelapse surgery was 21.7 months (95%CI, 13.9-29.5) and 26.0 months (95%CI, 18.4-33.7), respectively. Survival was significantly worse in patients with nonendometrioid histology (P < 0.0001). CONCLUSIONS: Surgery for UC relapse seems feasible with acceptable morbidity and high complete resection rates despite the multifocal patterns of relapse in a selected group of patients in a reference center for gynecological cancers. Larger scale studies are warranted to establish the value of surgery at relapse for UC.

Post-Radiation Therapy Imaging Appearances in Cervical Carcinoma.

Locally advanced and node-positive cervical cancers are usually treated with external beam radiation therapy and intracavitary brachytherapy with concomitant chemotherapy. In patients with locally advanced cervical cancer, imaging plays a vital role in pretreatment planning, assessment of primary tumor response to treatment, follow-up, and evaluation of treatment-related complications. Radiation therapy planning is crucial to successful local and regional control of disease. Patient selection criteria for radiation therapy with concomitant chemotherapy are described, as is assessment of treatment response of the primary cervical tumor at magnetic resonance (MR) imaging. Image interpretation can be challenging because of radiation therapy-related changes in the pelvic organs. Expected changes in the bladder, bowel, and bone marrow after radiation therapy are described, and multimodality imaging findings at computed tomography, MR imaging, and fluorine 18 fluorodeoxyglucose positron emission tomography are illustrated. Complications after radiation therapy have declined over recent years because of targeted radiation therapy. These complications can be divided into acute and chronic effects, where acute toxic effects occur within weeks of treatment. Chronic complications include cervical stenosis, small bowel stricture, fistula formation, and insufficiency fractures. Imaging is an essential tool in the care of patients with cervical cancer treated with chemotherapy and radiation therapy. The reporting radiologist should be familiar with the expected imaging appearances of the pelvic organs after radiation therapy, as well as potential complications, to avoid pitfalls in image interpretation.

Disseminated cancer in pregnancy: krukenberg tumour.

Disseminated cancer presenting in pregnancy is extremely rare and its presentation can easily be obscured by pregnancy and physiological changes that occur with it. This case describes a patient who was diagnosed incidentally following investigations for preeclampsia. Despite initially being thought to be of low risk, the final diagnosis was that of metastasis from a primary cancer of an unknown origin, most likely a gastric adenocarcinoma. Although patients are under thorough observation throughout their pregnancy, this case highlights the potential need for additional investigations or adjustment of current practices. It also draws attention to the lack of sufficient reporting of cancer in pregnancy, which, considering its rarity, greatly influences how patients are managed.

Biological efficacy of silk fibroin nanofiber membranes for guided bone regeneration.

The favorable biological properties of silk fibroin (SF) nanofiber membrane make it a good candidate for clinical applications as a device in bone and periodontal regenerative therapy. The purpose of this study is to evaluate the biocompatibility of the SF nanofiber membrane, and to examine its effect on bone regeneration in a rabbit calvarial model. To examine the biocompatibility of the electrospun SF membrane, we investigated cell proliferation, morphology, and differentiation. The bone regenerative efficacy of the membrane was evaluated in the calvarial defect of rabbits. The cell numbers and osteocalcin production labels were significantly increased in accordance with culture period. Cells had a stellate shape and broad cytoplasmic extensions on the membrane. The cells showed activity of ALPase that was comparable to culture dishes, and were calcified similarly to culture dishes. In in vivo tests, a complete bony union across the defects was observed after 8 weeks. At 12 weeks, the defect had completely healed with new bone. In conclusion, the SF nanofiber membrane was shown to possess good biocompatibility with enhanced bone regeneration and no evidence of any inflammatory reaction. These results strongly suggest that the SF membrane should be useful as a tool for guided bone regeneration.

Cardiovascular disease in renal allograft recipients is associated with elevated sialic acid or markers of inflammation.

BACKGROUND: Cardiovascular disease (CVD) is more common in patients with renal failure, even after renal transplantation. We wished to examine the relationship between markers of inflammation and CVD in stable renal transplant patients. METHODS: Ninety stable renal transplant outpatients with no recent illnesses or rejection were invited for study. Blood was drawn for a variety of inflammatory markers including total plasma sialic acid (SA) levels. RESULTS: Patients with CVD were significantly older than patients without (54 +/- 12 vs. 42 +/- 14 yr, p < 0.01) and had significantly lower total cholesterol (4.5 +/- 1.6 vs. 5.1 +/- 1.0 mmol/L, p < 0.01). Time from transplantation, present creatinine and blood pressure, smoking history were similar in both groups. Patients with CVD had significantly higher levels of SA (89.2 +/- 22.3 vs. 77.4 +/- 13.9 mg/dL, p = 0.01); fibrinogen [4.6 (2.2-6.7) vs. 3.6(1.9-5.7) g/L; p = 0.05); and C-reactive protein (CRP) [2.2 (1.5-8.0) vs 1.5 (0.7-3.0) microg/dL] than those without CVD. A logistic multiple linear regression analysis of the data with CVD as the dependent variable, and all the other parameters as independent variables, showed significant associations (F = 16.9; p < 0.001) with diastolic blood pressure (beta = 5.6; p = 0.02) and CRP (beta = 4.4; p = 0.04). CONCLUSIONS: This study suggests that inflammation is associated with a higher prevalence of cardiovascular disease in patients with renal allografts. The measurement of sialic acid as a risk factor may be superior to that of CRP in this group as its concentration is independent of renal function.