An external validation of the Candiolo nomogram in a cohort of prostate cancer patients treated by external-beam radiotherapy.

BACKGROUND: the aim of this study is to perform an external validation for the Candiolo nomogram, a predictive algorithm of biochemical and clinical recurrences in prostate cancer patients treated by radical Radiotherapy, published in 2016 on the journal "Radiation Oncology". METHODS: 561 patients, treated by Radiotherapy with curative intent between 2003 and 2012, were classified according to the five risk-classes of the Candiolo nomogram and the three risk-classes of the D'Amico classification for comparison. Patients were treated with a mean prostatic dose of 77.7 Gy and a combined treatment with Androgen-Deprivation-Therapy in 76% of cases. The end-points of the study were biochemical-progression-free-survival (bPFS) and clinical-Progression-Free-Survival (cPFS). With a median follow-up of 50 months, 56 patients (10%) had a biochemical relapse, and 30 patients (5.4%) a clinical progression. The cases were divided according to D'Amico in low-risk 21%, intermediate 40%, high-risk 39%; according to Candiolo very-low-risk 24%, low 37%, intermediate 24%, high 10%, very-high-risk 5%. Statistically, the Kaplan-Meier survival curves were processed and compared using Log-Rank tests and Harrell-C concordance index. RESULTS: The 5-year bPFS for the Candiolo risk-classes range between 98 and 38%, and the 5-year cPFS between 98 and 50% for very-low and very-high-risk, respectively. The Candiolo nomogram is highly significant for the stratification of both bPFS and cPFS (P < 0.0001), as well as the D'Amico classification (P = 0.004 and P = 0.001, respectively). For the Candiolo nomogram, the C indexes for bPFS and cPFS are 75 and 80%, respectively, while for D'Amico classification they are 64 and 69%, respectively. The Candiolo nomogram can identify a greater number of patients with low and very-low-risk prostate cancer (61% versus 21% according to D'Amico) and it better picks out patients with high and very-high-risk of recurrence, equal to only 15% of the total cases but subject to 48% (27/56) of biochemical relapses and 63% (19/30) of clinical progressions. CONCLUSIONS: the external validation of the Candiolo nomogram was overall successful with C indexes approximately 10% higher than the D'Amico control classification for bPFS and cPFS. Therefore, its clinical use is justified in prostate cancer patients before radical Radiotherapy. Trial registration Retrospectively registered.

Exploring the variability of radiomic features of lung cancer lesions on unenhanced and contrast-enhanced chest CT imaging.

PURPOSE: The aim of this methods work is to explore the different behavior of radiomic features resulting by using or not the contrast medium in chest CT imaging of non-small cell lung cancer. METHODS: Chest CT scans, unenhanced and contrast-enhanced, of 17 patients were selected from images collected as part of the staging process. The major T1-T3 lesion was contoured through a semi-automatic approach. These lesions formed the lesion phantoms to study features behavior. The stability of 94 features of the 3D-Slicer package Radiomics was analyzed. Feature discrimination power was quantified by means of Gini's coefficient. Correlation between distance matrices was evaluated through Mantel statistic. Heatmap, cluster and silhouette plots were applied to find well-structured partitions of lesions. RESULTS: The Gini's coefficient evidenced a low discrimination power, <0.05, for four features and a large discrimination power, around 0.8, for five features. About 90% of features was affected by the contrast medium, masking tumor lesions variability; thirteen features only were found stable. On 8178 combinations of stable features, only one group of four features produced the same partition of lesions with the silhouette width greater than 0.51, both on unenhanced and contrast-enhanced images. CONCLUSIONS: Gini's coefficient highlighted the features discrimination power in both CT series. Many features were sensitive to the use of the contrast medium, masking the lesions intrinsic variability. Four stable features produced, on both series, the same partition of cancer lesions with reasonable structure; this may merit being objects of further validation studies and interpretative investigations.

Prostate cancer dose-response, fractionation sensitivity and repopulation parameters evaluation from 25 international radiotherapy outcome data sets.

OBJECTIVE: This study was undertaken to model the biochemical free survival at 5 years and to evaluate the parameters defining dose-response curve, dose-fractionation radiosensitivity and repopulation. METHODS: It was carried out a literature search on Pubmed to retrieve data sets of patients treated with external beam radiation therapy of 1.8-4.0 Gy per fraction and overall treatment time of 3 to 10 weeks. 10 groups were identified, based on risk class and androgen deprivation therapy (ADT). Dose-response curve D50 (dose at 50% probability of control) and g50 (steepness), α/ß (dose-fractionation radiosensitivity), and repopulation parameters, dprolif and Tprolif , were calculated. Bootstrap-based cross-validation was performed and median and 95% CI (confidence interval) were evaluated. RESULTS: 25 data sets, including 20,310 patients, were considered. The median (95% CI) D50 and g50 values were 62 (CI 53 - 66) Gy and 1.6 (0.8 - 2.4). ADT patients showed lower values of D50 and g50 (57 ± 5 Gy and 1.1 ± 0.4) compared to no-ADT patients (65 ± 2 Gy and 2.3 ± 0.6), with p < 0.0001 and p = 0.002. If we did not consider any dependence on overall treatment time, the median (95% CI) value of α/ß was 1.4 (1.0 - 1.9) Gy with p < 0.0001 for all patients. The median values of dproli f and Tprolif were 0.0 to 0.3 Gy/d and 18-40 days. CONCLUSION: Dose-response curve resulted dependent on risk class and ADT, with higher steepness for no-ADT patients. Low values of dose-fractionation radiosensitivity were found, supporting the use of moderate hypofractionated radiotherapy in each risk class. A limited dependence on repopulation was observed. ADVANCES IN KNOWLEDGE: Prostate cancer response to moderate hypofractionated radiotherapy was reliably quantified considering risk class and androgen deprivation therapy.

A new form of the calibration curve in radiochromic dosimetry. Properties and results.

PURPOSE: This work describes a new form of the calibration curve for radiochromic dosimetry that depends on one fit parameter. Some results are reported to show that the new curve performs as well as those previously used and, more importantly, significantly reduces the dependence on the lot of films, the film orientation on the scanner, and the time after exposure. METHODS: The form of the response curve makes use of the net optical densities ratio against the dose and has been studied by means of the Beer-Lambert law and a simple modeling of the film. The new calibration curve has been applied to EBT3 films exposed at 6 and 15 MV energy beams of linear accelerators and read-out in transmission mode by means of a flatbed color scanner. Its performance has been compared to that of two established forms of the calibration curve, which use the optical density and the net optical density against the dose. Four series of measurements with four lots of EBT3 films were used to evaluate the precision, accuracy, and dependence on the time after exposure, orientation on the scanner and lot of films. RESULTS: The new calibration curve is roughly subject to the same dose uncertainty, about 2% (1 standard deviation), and has the same accuracy, about 1.5% (dose values between 50 and 450 cGy), as the other calibration curves when films of the same lot are used. Moreover, the new calibration curve, albeit obtained from only one lot of film, shows a good agreement with experimental data from all other lots of EBT3 films used, with an accuracy of about 2% and a relative dose precision of 2.4% (1 standard deviation). The agreement also holds for changes of the film orientation and of the time after exposure. CONCLUSIONS: The dose accuracy of this new form of the calibration curve is always equal to or better than those obtained from the two types of curves previously used. The use of the net optical densities ratio considerably reduces the dependence on the lot of films, the landscape/portrait orientation, and the time after exposure. This form of the calibration curve could become even more useful with new optical digital devices using monochromatic light.

Methods for comparing gridded inventories of atmospheric emissions--application for Milan province, Italy and the Greater Athens Area, Greece.

A set of methods has been compiled to compare gridded air emission inventories that have been derived, on the same spatial grid, using widely differing techniques. Top-down and bottom-up inventories for Milan, Italy and for the Greater Athens area (GAA), Greece were used to test and apply these methods. The applicability of each method to certain source sectors was assessed by conducting sensitivity analyses. Whilst some of the methods (such as regression calculations or the Moran coefficient) appeared very sensitive to variations of point source emissions, others (e.g. the construction of difference maps) proved more appropriate for characterizing line source differences. Area sources could best be dealt with by using the newly developed acceptability criterion. The development of these tools allows a reproducible comparison of sets of emission inventories and consequently supports developments towards improvement.