Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients

It is increasingly evident the necessity of new predictive tools for the treatment of pancreatic ductal adenocarcinoma in a personalized manner. We present a co-clinical trial testing the predictiveness of zPDX (zebrafish patient-derived xenograft) for assessing if patients could benefit from a therapeutic strategy (ClinicalTrials.gov: XenoZ, NCT03668418). zPDX are generated xenografting tumor tissues in zebrafish embryos. zPDX were exposed to chemotherapy regimens commonly used. We considered a zPDX a responder (R) when a decrease ≥50% in the relative tumor area was reported; otherwise, we considered them a non-responder (NR). Patients were classified as Responder if their own zPDX was classified as an R for the chemotherapy scheme she/he received an adjuvant treatment; otherwise, we considered them a Non-Responder. We compared the cancer recurrence rate at 1 year after surgery and the disease-free survival (DFS) of patients of both groups. We reported a statistically significant higher recurrence rate in the Non-Responder group: 66.7% vs. 14.3% (p = 0.036), anticipating relapse/no relapse within 1 year after surgery in 12/16 patients. The mean DFS was longer in the R-group than the NR-group, even if not statistically significant: 19.2 months vs. 12.7 months, (p = 0.123). The proposed strategy could potentially improve preclinical evaluation of treatment modalities and may enable prospective therapeutic selection in everyday clinical practice.

Radiomics AI prediction for head and neck squamous cell carcinoma (HNSCC) prognosis and recurrence with target volume approach

Objectives: To evaluate the performance of radiomics features extracted from planning target volume (PTV) and gross tumor volume (GTV) in the prediction of the death prognosis and cancer recurrence rate for head and neck squamous cell carcinoma (HNSCC). Methods: 188 HNSCC patients’ planning CT images with radiotherapy structures sets were acquired from Cancer Imaging Archive (TCIA). The 3D slicer (v. 4.10.2) with the PyRadiomics extension (Computational Imaging and Bioinformatics Lab, Harvard medical School) was used to extract radiomics features from the radiotherapy planning images. An in-house developed deep learning artificial neural networks (DL-ANN) model was used to predict death prognosis and cancer recurrence rate based on the features extracted from GTV and PTV of the CT images. Results: The PTV radiomics features with DL-ANN model could achieve 77.7% accuracy with overall AUC equal to 0.934 and 0.932 when predicting HNSCC-related death prognosis and cancer recurrence respectively. Furthermore, the DL-ANN model can achieve an accuracy of 74.3% with AUC equal to 0.947 and 0.956 for the HNSCC-related death prognosis and cancer recurrence respectively using GTV features. Conclusion: Using both GTV and PTV radiomics features in the DL-ANN model, can aid in predicting HNSCC-related death prognosis and cancer recurrence. Clinicians may find it helpful in formulating different treatment regimens and facilitate personized medicine based on the predicted outcome when performing GTV and PTV delineation. Advances in knowledge: Radiomics features of GTV and PTV are reliable prognosis and recurrence predicting tools, which may help clinicians in GTV and PTV delineation to facilitate delivery of personalized treatment.

Urethral recurrence after radical cystoprostatectomy: Experience from a high-volume tertiary referral centre

Objectives: To report our urethral surveillance programme and urethral cancer recurrence rate following radical cystoprostatectomy (RC). Patients and methods: A retrospective analysis of clinical and histopathological data of men who underwent RC and urethral surveillance, between January 2011 and October 2016. Results: RC was performed for 491 men; 31 and 19 men had a synchronous (malignancy, n = 10, 32.3%) and interval (malignancy, n = 6, 31.6%) urethrectomy, respectively. The remaining 441 men underwent surveillance; 183 (41.5%) men had at least one urethroscopy, 14 (3.2%) urethrectomies were performed and 12 (2.7%) specimens confirmed urethral recurrence (UR). Within the URs, 7/12 (58.3%) men presented symptomatically and 5/12 (41.7%) were detected through surveillance. At a median (interquartile range) follow-up of 21.8 (9.7–36.7) months, the 2-year disease-specific survival in men who had synchronous urethrectomy was 71.4% (versus no urethrectomy (84.6%) interval urethrectomy (92.9%) and urethrectomy for recurrence (83.8%)). Conclusion: UR following RC is low in men without risk factors for urethral disease. Annual urethroscopy and urine cytology may not be feasible and appropriate in all men after RC, and does not appear to impact survival at 2 years. A risk-adapted approach may allow the avoidance of annual urethroscopy in asymptomatic men post RC. Level of Evidence: 3b