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Background: Patients with muscle-invasive bladder cancer (MIBC) who receive radiotherapy with curative intent are followed by imaging, cystoscopy, and urine cytology. However, interpretation of cytology and cystoscopy is hampered by the impact of ionizing radiation on cells. Objective: To assess the diagnostic performance of a genomic urine assay to detect urinary tract recurrences in patients with MIBC treated by (chemo)radiation. Design, setting, and participants: Patients with nonmetastatic MIBC who underwent (chemo)radiation with curative intent from 2016 to 2020 were prospectively included. Follow-up consisted of cystoscopy and upper tract imaging. Prior to cystoscopy, a urine sample was analyzed to assess mutations in the genes FGFR3, HRAS, and TERT and methylation of OTX1, TWIST1, and ONECUT2. The treating physician was blinded for the assay result. Outcome measurements and statistical analysis: The primary endpoint was a urinary tract recurrence. Cross-sectional sensitivity, specificity, and negative predictive value (NPV) were analyzed using a previously developed logistic regression model for the detection of bladder cancer with this assay. The secondary endpoint was the risk of a future urinary tract recurrence following a positive test and negative cystoscopy/imaging, using a time-dependent Cox proportional hazard analysis. Results and limitations: A total of 143 patients were included, and 503 urine samples were analyzed. The median study duration was 20 mo (interquartile range [IQR] 10–33), and the median time to a recurrence was 16 mo (IQR 12–26). In 27 patients, 32 urinary tract recurrences were diagnosed, including three upper tract tumors. Of 32 recurrences, 18 (56%) had a concomitant urine test available. The diagnostic model had an area under the curve of 0.80 (95% confidence interval [CI] 0.69–0.90) with corresponding sensitivity, specificity, and NPV of 78 (95% CI 52–94), 77% (95% CI 73–81), and 99% (95% CI 97–100). When taking into account the anticipatory effect of the test, 28/32 (88%) recurrences were detected. A Cox regression analysis showed a hazard ratio of 14.8 for the development of a future recurrence (p < 0.001). A major limitation was the lack of a concomitant urine test result in 14/32 (44%) recurrences. Conclusions: A genomic urine assay detected urinary tract recurrences after (chemo)radiation in patients with MIBC, and a positive test was strongly associated with future recurrences. Although validation in a large cohort is warranted, the test has the potential to limit frequent cystoscopies. Patient summary: Radiotherapy is a bladder-sparing treatment in patients with bladder cancer. After treatment, these patients undergo visual inspection of the bladder by cystoscopy to detect possible recurrences. However, interpretation of cystoscopy is difficult due to the effects of radiation on the bladder lining. Hence, we analyzed the diagnostic value of a molecular urine test to detect recurrent disease in bladder cancer patients treated by radiotherapy, and we showed that the urine test has the potential to limit the number of cystoscopies.

Purpose: To develop a single NTCP model for grade ≥ 2 late rectal bleeding (G2 LRB) after conventional or hypofractionated radiotherapy for prostate cancer. Methods and Materials: The development dataset consisted of prostate cancer patients (n = 656) previously randomized to conventional (39 x 2 Gy) or hypofractionated (19 x 3.4 Gy) external beam radiotherapy with N = 89 G2 LRB cases. Candidate predictors were obtained from literature. We fitted five separate logistic regression models to the data, each with one of the following dose parameters as candidate predictors in biological effective dose (BED), assuming α/β = 3 Gy: Equivalent uniform dose (EUD) with n = 0.1, EUD with n = 0.2, the relative volume receiving ≥ 111.9 Gy in BED (V111.9, the equivalent of physical V70 for a conventional schedule), minimum BED to the hottest 0.1 cm3 (D0.1cm3) or 2 cm3 (D2cm3). Previous abdominal surgery was included in every model and fractionation schedule was tested as predictor in each model. A sensitivity analysis was performed by varying the α/β-ratio, n and dose-volume cutoff. Results: The pre-selected candidate dosimetric predictor and previous abdominal surgery were significantly associated with the outcome in all five models. Fractionation schedule was eliminated by the backward scheme in only the EUD (n = 0.1), D0.1cm3 and D2cm3-based models. In internal validation these models showed AUC’s of 0.64, 0.60 & 0.62, respectively. The sensitivity analyses showed that EUD models with n ≥ 0.15 and / or α/β ≥ 4 Gy failed, and EUD models based on α/β = 2 Gy with n = 0.05–0.2 showed good fits as well. Conclusions: Our trial data set with different fractionation schedules offered the unique possibility to generate unbiased BED-based models. EUD (n = 0.1), D0.1cm3 and D2cm3 performed overall best in predicting G2 LRB; with α/β = 2 Gy equally good models were obtained. External validation is required to confirm our results.

Background and purpose: External beam radiotherapy for prostate cancer deposits incidental dose to a region surrounding the target volume. Previously, an association was identified between tumor control and incidental dose for patients treated with conventional radiotherapy. We investigated whether such an association exists for patients treated using intensity modulated radiotherapy (IMRT) and tighter margins. Materials and methods: Computed tomography scans and three-dimensional treatment planning dose distributions were available from the Dutch randomized HYPRO trial for 397 patients in the standard fractionation arm (39 × 2 Gy) and 407 patients in the hypofractionation arm (19 × 3.4 Gy), mainly delivered using online image-guided IMRT. Endpoint was any treatment failure within 5 years. A mapping of 3D dose distributions between anatomies was performed based on distance to the surface of the prostate delineation. Mean mapped dose distributions were computed for patient groups with and without failure, obtaining dose difference distributions. Random patient permutations were performed to derive p values and to identify relevant regions. Results: For high-risk patients treated in the conventional arm, higher incidental dose was significantly associated with a higher probability of tumor control in both univariate and multivariate analysis. The locations of the excess dose mainly overlapped with the position of obturator internus muscles at about 2.5 cm from the prostate surface. No such relationship could be established for intermediate-risk patients. Conclusions: An association was established between reduced treatment failure and the delivery of incidental dose outside the prostate for high-risk patients treated using conventionally fractionated IMRT.

Introduction: The COVID-19 outbreak has affected care for non-COVID diseases like cancer. We evaluated the impact of the COVID-19 outbreak on prostate cancer care in the Netherlands. Methods: Prostate cancer diagnoses per month in 2020–2021 versus 2018–2019 were compared based on preliminary data of the Netherlands Cancer Registry (NCR) and nationwide pathology network. Detailed data was retrieved from the NCR for the cohorts diagnosed from March-May 2020 (first COVID-19 wave) and March-May 2018–2019 (reference). Changes in number of diagnoses, age, disease stage and first-line treatment were compared. Results: An initial decline of 17% in prostate cancer diagnoses during the first COVID-19 wave was observed. From May onwards the number of diagnoses started to restore to approximately 95% of the expected number by the end of 2020. Stage at diagnosis remainedstable over time. In low-risk localised prostate cancer radical prostatectomy was conducted more often in week 9–12 (21% versus 12% in the reference period; OR=1.9, 95% CI; 1.2–3.1) and less active surveillance was applied (67% versus 78%; OR=0.6, 95% CI; 0.4–0.9). In the intermediate-risk group, a similar change was observed in week 13–16. Radical prostatectomy volumes in 2020 were comparable to 2018–2019. Conclusion: During the first COVID-19 wave the number of prostate cancer diagnoses declined. In the second half of 2020 this largely restored although the number remained lower than expected. Changes in treatment were temporary and compliant with adapted guidelines. Although delayed diagnoses could result in a less favourable stage distribution, possibly affecting survival, this seems not very likely.

Spinach is one of the most important green-leafy vegetables, consumed worldwide, and its intake is beneficial for human beings. In this crop, produce yield and quality are closely related to plant nitrogen (N) nutrition. A precise supply of N is also essential for high environmental and economic sustainability. Main aims of the work were: i) to establish relationships between produce yield or quality and mineral N availability in the root zone; and ii) to define an optimal mineral N level to be maintained in the root zone for spinach. Eight experiments were carried out during a four-year-long period under typical Mediterranean climate conditions. Different amounts of N fertilisers were supplied leading to twenty different levels of mineral N in the root zone. Experimental measurements included climate parameters, plant growth, tissue and soil analyses, produce yield and quality indicators. A segmented linear model significantly represented the relationship between crop yield (1.7 to 21.7 t ha–1) and soil mineral N concentration (7.6 to 41.0 mg kg–1). Basing on this model, an optimal mineral N threshold was fixed at 23.4 mg kg–1. Above this threshold, crop yield did not show any significant variations as well as tissue characteristics and produce quality. Plants grown under suboptimal N levels showed reduction in growth, tissue mineral (nutrients) content, and SPAD index. The proposed models could be implemented in fertilisation protocols for the optimization of N supply and the estimation of spinach growth and yield.

An increasing trend was observed over the last years in the modelling of soil-plant-management interactions of protected crops, mainly as an adaptation of approaches originally developed for field crops. The variety of modelling approaches used world-wide reflects the difficulty of unifying physiological principles across various crops (plant types). The heterogeneity of software development techniques (typically based on procedural principles) has been another obstacle to the progress of research in this field, since it hampered model extension and re-usability. This paper describes and discusses the scientific basis, the design, implementation and perspectives in modelling greenhouse crops. Generic modular architectures developed according to up to date software technologies (.NET, Java) were identified and proposed as valuable for the design, implementation, verification and comparison of process-based modelling approaches. On this basis, the authors argue that the combination of good software engineering with sound crop science can enhance the rate of advance in crop modelling for protected crops.