Enhancing Nasopharyngeal Carcinoma Survival Prediction: Integrating Pre- and Post-Treatment MRI Radiomics with Clinical Data.

Recurrences are frequent in nasopharyngeal carcinoma (NPC) despite high remission rates with treatment, leading to considerable morbidity. This study aimed to develop a prediction model for NPC survival by harnessing both pre- and post-treatment magnetic resonance imaging (MRI) radiomics in conjunction with clinical data, focusing on 3-year progression-free survival (PFS) as the primary outcome. Our comprehensive approach involved retrospective clinical and MRI data collection of 276 eligible NPC patients from three independent hospitals (180 in the training cohort, 46 in the validation cohort, and 50 in the external cohort) who underwent MRI scans twice, once within 2 months prior to treatment and once within 10 months after treatment. From the contrast-enhanced T1-weighted images before and after treatment, 3404 radiomics features were extracted. These features were not only derived from the primary lesion but also from the adjacent lymph nodes surrounding the tumor. We conducted appropriate feature selection pipelines, followed by Cox proportional hazards models for survival analysis. Model evaluation was performed using receiver operating characteristic (ROC) analysis, the Kaplan-Meier method, and nomogram construction. Our study unveiled several crucial predictors of NPC survival, notably highlighting the synergistic combination of pre- and post-treatment data in both clinical and radiomics assessments. Our prediction model demonstrated robust performance, with an accuracy of AUCs of 0.66 (95% CI: 0.536-0.779) in the training cohort, 0.717 (95% CI: 0.536-0.883) in the testing cohort, and 0.827 (95% CI: 0.684-0.948) in validation cohort in prognosticating patient outcomes. Our study presented a novel and effective prediction model for NPC survival, leveraging both pre- and post-treatment clinical data in conjunction with MRI features. Its constructed nomogram provides potentially significant implications for NPC research, offering clinicians a valuable tool for individualized treatment planning and patient counseling.

Retrospective Analysis for Dose Reduction to Organs at Risk with New Personalized Breast Holder (PERSBRA) in Left Breast IMRT.

This study evaluated dose differences in normal organs at risk, such as the lungs, heart, left anterior descending artery (LAD), right coronary artery, left ventricle, and right breast under personalized breast holder (PERSBRA), when using intensity-modulated radiation therapy (IMRT). This study evaluated the radiation protection offered by PERSBRA in left breast cancer radiation therapy. Here, we retrospectively collected data from 24 patients with left breast cancer who underwent breast-conserving surgery as well as IMRT radiotherapy. We compared the dose differences in target coverage and organs at risk with and without PERSBRA. For target coverage, tumor prescribed dose 95% coverage, conformity index, and homogeneity index were evaluated. For organs at risk, we compared the mean heart dose, mean left ventricle dose, LAD maximum and mean dose, mean left lung receiving 20 Gy, 10 Gy, and 5 Gy of left lung volume, maximum and mean coronary artery of the right, maximum of right breast, and mean dose. Good target coverage was achieved with and without PERSBRA. When PERSBRA was used with IMRT, the mean dose of the heart decreased by 42%, the maximum dose of LAD decreased by 26.4%, and the mean dose of LAD decreased by 47.0%. The mean dose of the left ventricle decreased by 54.1%, the volume (V20) of the left lung that received 20 Gy decreased by 22.8%, the volume (V10) of the left lung that received 10 Gy decreased by 19.8%, the volume (V5) of the left lung that received 5 Gy decreased by 15.7%, and the mean dose of the left lung decreased by 23.3%. Using PERSBRA with IMRT greatly decreases the dose to organs at risk (left lung, heart, left ventricle, and LAD). This study found that PERSBRA with IMRT can achieve results similar to deep inspiration breath-hold radiotherapy (DIBH) in terms of reducing the heart radiation dose and the risk of developing heart disease in patients with left breast cancer who cannot undergo DIBH.

Correlation between drug sensitivity profiles of circulating tumour cell-derived organoids and clinical treatment response in patients with pancreatic ductal adenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging. METHODS: Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed. RESULTS: A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts. CONCLUSIONS: CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach.

High-resolution melting and real-time PCR for quantification and detection of drug-resistant HBV mutants in a single amplicon.

BACKGROUND: Antiviral therapy by nucleoside/nucleotide analogues (NAs) effectively reduces HBV replication in chronic hepatitis B (CHB) patients. Because long-term NA treatments will eventually select for drug-resistant mutants, early detection of mutants and frequent monitoring of viral loads is crucial for successful NA therapy. Because no efficient test for one-tube quantification and qualification of various HBV-resistant mutants exists, we propose to use high-resolution melting (HRM) analysis in combination with real-time PCR to achieve this unmet need. METHODS: We developed a single amplicon for detecting HBV mutants resistant to lamivudine (LMV), adefovir (ADV) and entecavir (ETV), which are commonly used for CHB treatment. Our design consists of two steps: real-time PCR for viral quantification, and hybridization probe HRM analysis for detection of specific drug-resistant mutants. RESULTS: Assay quantification was accurate (R=0.98) for viral loads from 10(3) to 10(9) copies/ml. HRM analysis produced distinct melting temperatures that clearly distinguished the mutants, rtM204V/I (LMV), rtA181V and rtN236T (ADV), and rtT184G and rtM250V (ETV), from their respective wild types. The assay detected mutants at only 10-25% of the HBV population. The clinical applicability of this assay was tested in a pilot study with serial samples from patients receiving LMV treatment. CONCLUSIONS: Flexibility, speed and cost-efficiency are additional benefits unique to our assay. The clinical sample results further support the feasibility of applying our design to frequent and long-term monitoring of CHB patients receiving NA treatments in the clinical setting.

Regulation of cyst wall protein promoters by Myb2 in Giardia lamblia.

Myb family transcription factors are important in regulating cell proliferation, differentiation, and cell cycle progression. Giardia lamblia differentiates into infectious cysts to survive outside of the host. During encystation, genes encoding cyst wall proteins (CWPs) are coordinately induced. We have identified an encystation-induced Myb2 protein, which binds to the promoter regions of the cwp genes and myb2 itself in vitro. To elucidate the role of Myb2 in G. lamblia, we tested the hypothesis that Myb2 can activate encystation-induced genes. We found that overexpression of Myb2 resulted in an increase of expression of CWP1 at both protein and mRNA levels. Interestingly, the Myb2-overexpressing trophozoites had increased capability to differentiate into cysts. In cotransfection assays, Myb2 was able to transactivate the cwp promoters and its own promoter in vivo, suggesting that its gene can be positively autoregulated. Moreover, deletion of the N- or C-terminal domain resulted in a decrease of transactivation and autoregulation function of Myb2. We also found that the promoter of a newly identified encystation-induced gene, the giardial myeloid leukemia factor-like gene, has the Myb2 binding sites and that its mRNA levels were increased by Myb2 overexpression. Chromatin immunoprecipitation assays confirmed that Myb2 was bound to the promoters with its binding sites. Transfection of the myb2 antisense construct reduced the levels of the cwp1 transcripts and cyst formation. Our results suggest that Myb2 is a potent transactivator of the cwp genes and other endogenous genes and plays an important role in G. lamblia differentiation into cysts.