How smart is artificial intelligence in organs delineation? Testing a CE and FDA-approved Deep-Learning tool using multiple expert contours delineated on planning CT images.

Background: A CE- and FDA-approved cloud-based Deep learning (DL)-tool for automatic organs at risk (OARs) and clinical target volumes segmentation on computer tomography images is available. Before its implementation in the clinical practice, an independent external validation was conducted. Methods: At least a senior and two in training Radiation Oncologists (ROs) manually contoured the volumes of interest (VOIs) for 6 tumoral sites. The auto-segmented contours were retrieved from the DL-tool and, if needed, manually corrected by ROs. The level of ROs satisfaction and the duration of contouring were registered. Relative volume differences, similarity indices, satisfactory grades, and time saved were analyzed using a semi-automatic tool. Results: Seven thousand seven hundred sixty-five VOIs were delineated on the CT images of 111 representative patients. The median (range) time for manual VOIs delineation, DL-based segmentation, and subsequent manual corrections were 25.0 (8.0-115.0), 2.3 (1.2-8) and 10.0 minutes (0.3-46.3), respectively. The overall time for VOIs retrieving and modification was statistically significantly lower than for manual contouring (p<0.001). The DL-tool was generally appreciated by ROs, with 44% of vote 4 (well done) and 43% of vote 5 (very well done), correlated with the saved time (p<0.001). The relative volume differences and similarity indexes suggested a better inter-agreement of manually adjusted DL-based VOIs than manually segmented ones. Conclusions: The application of the DL-tool resulted satisfactory, especially in complex delineation cases, improving the ROs inter-agreement of delineated VOIs and saving time.

Unraveling the safety of adjuvant radiotherapy in prostate cancer: impact of older age and hypofractionated regimens on acute and late toxicity - a multicenter comprehensive analysis.

Background: The objective of this study was to assess the impact of age and other patient and treatment characteristics on toxicity in prostate cancer patients receiving adjuvant radiotherapy (RT). Materials and methods: This observational study (ICAROS-1) evaluated both acute (RTOG) and late (RTOG/EORTC) toxicity. Patient- (age; Charlson's comorbidity index) and treatment-related characteristics (nodal irradiation; previous TURP; use, type, and duration of ADT, RT fractionation and technique, image-guidance systems, EQD2 delivered to the prostate bed and pelvic nodes) were recorded and analyzed. Results: A total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/ß=1.5) was 71.4 Gy. The majority of patients (75.4%) were treated with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Acute G3 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 0.5% and 1.3%, respectively. No patients experienced >G3 acute toxicity. The multivariable analysis of acute toxicity (binomial logistic regression) showed a statistically significant association between older age (> 65) and decreased odds of G≥2 GI acute toxicity (OR: 0.569; 95%CI: 0.329-0.973; p: 0.040) and decreased odds of G≥2 GU acute toxicity (OR: 0.956; 95%CI: 0.918-0.996; p: 0.031). The 5-year late toxicity-free survival rates for G≥3 GI and GU toxicity were 98.1% and 94.5%, respectively. The only significant correlation found (Cox's regression model) was a reduced risk of late GI toxicity in patients undergoing hypofractionation (HR: 0.38; 95% CI: 0.18-0.78; p: 0.008). Conclusions: The unexpected results of this analysis could be explained by a "response shift bias" concerning the protective effect of older age and by treatment in later periods (using IMRT/VMAT) concerning the favorable effect of hypofractionation. However, overall, the study suggests that age should not be a reason to avoid adjuvant RT and that the latter is well-tolerated even with moderately hypofractionated regimens.

COVID-19 Pandemic-Adapted Radiotherapy Guidelines: Are They Really Followed?

BACKGROUND: In our department, we provided guidelines to the radiation oncologists (ROs) regarding the omission, delay, or shortening of radiotherapy (RT). The purpose was to reduce the patients' exposure to the hospital environment and to minimize the departmental overcrowding. The aim was to evaluate the ROs' compliance to these guidelines. METHODS: ROs were asked to fill out a data collection form during patients' first visits in May and June 2020. The collected data included the ROs' age and gender, patient age and residence, RT purpose, treated tumor, the dose and fractionation that would have been prescribed, and RT changes. The chi-square test and binomial logistic regression were used to analyze the correlation between the treatment prescription and the collected parameters. RESULTS: One hundred and twenty-six out of 205 prescribed treatments were included in this analysis. Treatment was modified in 61.1% of cases. More specifically, the treatment was omitted, delayed, or shortened in 7.9, 15.9, and 37.3% of patients, respectively. The number of delivered fractions was reduced by 27.9%. A statistically significant correlation (p = 0.028) between younger patients' age and lower treatment modifications rate was recorded. CONCLUSION: Our analysis showed a reasonably high compliance of ROs to the pandemic-adapted guidelines. The adopted strategy was effective in reducing the number of admissions to our department.

Radiotherapy of Prostate Carcinoma: A Comparison of the Predictive Role of EAU Versus NCCN Risk Stratification Systems.

BACKGROUND/AIM: To compare the predictive efficacy of National Comprehensive Cancer Network (NCCN) and European Association of Urology (EAU) risk stratification systems in radiotherapy of prostate cancer. PATIENTS AND METHODS: One-thousand-nine-hundred-nine patients treated with definitive (1,074), adjuvant (381), and salvage radiotherapy (454) were analysed. RESULTS: Both systems significantly predicted biochemical-relapse-free-survival, metastasis-free-survival, and disease-free-survival, while only the NCCN system correlated with local-control in the definitive radiotherapy group. In the adjuvant setting, both systems failed to predict all outcomes. In the salvage setting, only the NCCN system significantly predicted biochemical-relapse-free-survival, metastasis-free-survival and disease-free-survival. CONCLUSION: This analysis confirms the efficacy of both systems in definitive radiotherapy and suggests the utility of the NCCN also in salvage radiotherapy.

Radiotherapy of prostate cancer: impact of treatment characteristics on the incidence of second tumors.

BACKGROUND: It has been hypothesized that radiotherapy (RT) techniques delivering radiations to larger volumes (IMRT, VMAT) are potentially associated with a higher risk of second primary tumors. The aim of this study was to analyse the impact of RT technique (3D-CRT vs IMRT/VMAT) on the incidence of second tumors in prostate cancer (PCa) patients. METHODS: A retrospective study on 2526 previously irradiated PCa patients was performed. Patients were treated with 3D-CRT (21.3%), IMRT (68.1%), or VMAT (10.6%). Second tumors incidence was analysed in 3 categories: pelvic, pelvic and abdominal, and "any site". The correlation with RT technique was analysed using log-rank test and Cox's proportional hazard method. RESULTS: With a median follow-up of 72 months (range: 9-185), 92 (3.6%) cases of second tumors were recorded with 48 months (range: 9-152) median interval from RT. Actuarial 10-year second tumor free survival (STFS) was 87.3%. Ten-year STFS in patients treated with 3D-CRT and IMRT/VMAT was 85.8 and 84.5%, respectively (p: .627). A significantly higher 10-year cumulative incidence of second tumors in the pelvis was registered in patients treated with IMRT/VMAT compared to 3D-CRT (10.7% vs 6.0%; p: .033). The lower incidence of second pelvic cancers in patients treated with 3D-CRT was confirmed at multivariable analysis (HR: 2.42, 95%CI: 1.07-5.47, p: .034). CONCLUSIONS: The incidence of second pelvic tumors after RT of PCa showed a significant correlation with treatment technique. Further analyses in larger series with prolonged follow-up are needed to confirm these results.

Radiotherapy Plus GnRH Analogue Versus High Dose Bicalutamide: A Case Control Study.

BACKGROUND/AIM: Radiotherapy (RT) with adjuvant hormone therapy (HT) improves prognosis in prostate cancer (PC) patients. Gonadotrophin-releasing hormone agonist (GnRHa) with luteinizing hormone-releasing hormone (LH-RH) analogues is the standard HT. High-dose antiandrogen therapy also improves survival in patients with locally advanced PC. The aim of this study was to compare the results of patients treated with RT plus GnRHa and patients treated with RT plus bicalutamide. PATIENTS AND METHODS: Our institutional PC database was used to identify patients treated with definitive or postoperative RT +/- HT which were included in this study. RESULTS: Three hundred and eighteen patients were retrospectively reviewed (median follow-up=56 months). Five-year biochemical relapse-free survival was 85.5% and 88.3% in patients treated with GnRHa and bicalutamide, respectively (p=0.712). CONCLUSION: Bicalutamide may be offered as an adjuvant treatment to RT in patients who refuse GnRHa because of related side effects. Furthermore, our study justifies randomized trials comparing RT plus GnRHa and RT plus bicalutamide.

Dominant intraprostatic lesion boosting in sexual-sparing radiotherapy of prostate cancer: A planning feasibility study.

AIM: Radical radiotherapy of prostate cancer requires a relatively high dose to achieve an optimal tumor control probability and a reduced dose to the critical structures related to the sexual function (S_OARs) in order to avoid erectile dysfunction. The aim of this study was to perform a planning feasibility analysis of a 3-level dose prescription with Simultaneous Integrated Boost (SIB) on the dominant intraprostatic lesion (DIL) and with S_OARs sparing. MATERIAL AND METHODS: Twelve patients with clinically localized intermediate risk prostate cancer were included. The prostate, seminal vescicles, and DIL Clinical Target Volumes were delineated on rigid fused MRI-CT simulation images using mp-MRI as a separate guide. A 5 mm margin was added to define the PTVs. Penile bulb (PB), corpora cavernosa (CC), internal pudendal arteries (IPAs) and neurovascular bundles were contoured as S_OARs. The following doses were prescribed in 25 fractions: 56.25 Gy to PTVsv, 67.50 Gy to PTVp, and 75 Gy to PTVdil. Standard plans (SD-VMAT) were created to fulfil targets coverage and Quantec constraints for conventional OARs (SD_OARs: rectum, bladder, and femoral heads). For each patient, a new "sexual-sparing" plan (SS-VMAT) was created adding new objectives for S_OARs with priority to minimize mean doses to IPAs, CC, and PB. Dose-volume histogram end points were compared between the 2 plans using Wilcoxon test. RESULTS: D98% were >95% of prescribed doses for all targets and techniques. No significant differences were found in sparing SD_OARs for considered metrics. Regarding S_OARs, SS_VMAT plans provided a significant reduction of the dose. Mean dose reduction for IPAs, CC, PB, and neurovascular bundles was 32.4% (11.2 Gy, p = 0.002), 22.5% (4.1 Gy, p = 0.006), 10.0% (4.6 Gy, p = 0.010), and 2.6% (1.8 Gy, p = 0.020), respectively. CONCLUSIONS: We showed that a significant dose sparing for S_OARs using VMAT-SIB strategy is feasible allowing "sexual-sparing" and highly conformal plans with dose escalation to the DIL.

Tailored postoperative treatment of prostate cancer: final results of a phase I/II trial.

BACKGROUD: The European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP. MATERIALS AND METHODS: This phase I/II trial treatment was designed to improve 5-year bDFS from ~ 75 to 90%. Patients were consecutively enrolled using the following inclusion criteria: age < 80 years, histological diagnosis of prostate adenocarcinoma without known metastases, stage pT2-4N0-1, and Eastern Cooperative Oncology Group performance status of 0-2. All patients had at least one of these pathologic features: capsular perforation, positive surgical margins, seminal vesicle invasion, and pelvic lymph nodes involvement. A minimum dose of 64.8 Gy to the tumor bed was delivered in all patients. Depending on tumor characteristics at diagnosis, patients received a higher dose (70.2 Gy; 85.4%) and/or prophylactic pelvic lymph nodes irradiation (57.7%) and/or HT (69.1%). Biochemical relapse was defined as two consecutive rising prostate-specific antigen (PSA) values > 0.2 ng/ml. RESULTS: A total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06 ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37-120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively. CONCLUSION: A higher 5-year bDFS (92.9%) was recorded compared to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. (ClinicalTrials.gov: NCT03169933).

Postoperative Hypofractionated Radiation Therapy in Prostate Carcinoma: A Systematic Review.

BACKGROUND/AIM: A systematic review on toxicity, local control (LC), overall survival (OS), and biochemical relapse-free survival (bRFS) after postoperative hypofractionated radiotherapy (HFRT) on prostate cancer (PCa) was performed. MATERIALS AND METHODS: Based on the PRISMA methodology, studies reporting clinical results after adjuvant or salvage HFRT were included. RESULTS: A total of 1,208 patients from 17 eligible studies were included. Median follow-up was 30 months. No case of severe acute gastrointestinal (GI) toxicity was recorded. Grade ≥3 acute genitourinary (GU) toxicity ranged between 0% and 3%. Different rates of grade ≥2 late GI (range=0-8.7%) and GU (range=0-66%) toxicity were recorded. Encouraging results on LC, OS, and bRFS were reported. CONCLUSION: Acute toxicity does not seem to be increased in patients receiving postoperative HFRT, but the results of late-GU toxicity are conflicting. Further prospective studies are needed before including postoperative HFRT in clinical practice.

Hypofractionated Postoperative IMRT in Prostate Carcinoma: A Phase I/II Study.

AIM: To report the outcome of hypofractionated radiotherapy after radical prostatectomy (RP) for prostate cancer (PCa) using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT). PATIENTS AND METHODS: A total of 124 patients with PCa at high risk of relapse after RP or diagnosis of biochemical relapse were included. Patients received 62.5 Gy to the prostate bed and 45 Gy to pelvic nodes in 25 fractions. Androgen-suppressive therapy was prescribed based on National Comprehensive Cancer Network risk categories. RESULTS: Median follow-up was 30 months. Only two patients (1.6%) developed grade 3 or more acute toxicity: one grade 3 skin toxicity (0.8%) and one grade 4 genitourinary toxicity (0.8%). Grade 2 acute gastrointestinal and genitourinary toxicity was recorded in 24.2% and 17.7% of patients, respectively. Five-year grade 2 or more gastrointestinal and genitourinary toxicity was 1.1% and 7.3%, respectively. Five-year biochemical relapse-free survival was 86.5%. CONCLUSION: After RP, hypofractionated IMRT-SIB demonstrated a favorable toxicity profile and encouraging results in terms of relapse-free survival.

11C-choline PET/CT detects the site of relapse in the majority of prostate cancer patients showing biochemical recurrence after EBRT.

PURPOSE: The aim of this retrospective study was to evaluate the usefulness and the detection rate of (11)C-choline PET/CT in a population of patients with prostate cancer (PC), exclusively treated with external beam radiotherapy (EBRT) as primary treatment, who showed biochemical relapse. MATERIALS AND METHODS: We enrolled 140 patients showing a serum PSA level >2 ng/mL (mean 8.6 ng/mL, median 5 ng/mL, range 2 - 60 ng/mL). All patients had been treated with EBRT to the prostate gland and prostatic fossa with doses ranging from 70 to 76 Gy in low-risk patients (T1/T2 and/or serum PSA <10 ng/mL) and escalating to >76 Gy (range 76 - 81 Gy) in high-risk patients (T3/T4 and/or serum PSA >10 ng/mL). Of the 140 patients, 53 were receiving androgen deprivation therapy at the time of the scan. All positive (11)C-choline PET/CT findings were validated by transrectal ultrasound-guided biopsy or at least 12 months of follow-up with contrast-enhanced CT, MR, bone scintigraphy or a repeated (11)C-choline PET/CT scan. The relationships between the detection rate of (11)C-choline PET/CT and the factors PSA level, PSA kinetics, Gleason score, age, time to relapse and SUV max in patients with positive findings were analysed. RESULTS: (11)C-Choline PET/CT detected the site of relapse in 123 of the 140 patients with a detection rate of 87.8 % (46 patients showed local relapse, 31 showed local and distant relapse, and 46 showed only distant relapse). In patients with relapse the mean serum PSA level was 9.08 ng/mL (median 5.1 ng/mL, range 2 - 60 ng/mL), the mean PSA doubling time was 5.6 months (median 3.5 months, range 0.4 - 48 months), and the mean PSA velocity was 15 ng/mL/year (median 8.8 ng/mL/year, range 0.4 - 87 ng/mL/year). Of the 123 patients with relapse, 77 (62.6 %) showed distant relapse with/without local relapse, and of these 77, 31 (40.2 %) showed oligometastatic disease (one or two distant lesions: lymph node lesions only in 16, bone lesions only in 14, and lymph node lesions and bone lesions in 1). In univariate and multivariate analyses PSA kinetics was the only variable affecting (11)C-choline PET/CT detection rate. A significant correlation between PSA kinetics and site of recurrence (local relapse only vs. distant metastasis) was also observed. CONCLUSION: The detection rate of (11)C-choline PET/CT in patients with PC showing biochemical recurrence after EBRT as primary treatment is relatively high (87.8 %). (11)C-Choline PET/CT was able to detect extraprostatic disease in the 62.6 % of patients. Considering this high detection rate, (11)C-choline PET/CT could have clinical usefulness in the management of these PC patients, but this should be confirmed in future studies.

Evaluating the influence of the Siemens IGRT carbon fibre tabletop in head and neck IMRT.

BACKGROUND AND PURPOSE: To investigate the impact of a commercial IMRT/IGRT carbon-fibre tabletop in radiotherapy planning optimization and clinical dose distribution. MATERIALS AND METHODS: In this investigation the Siemens IGRT carbon fibre tabletop, routinely used for IMRT treatments in our Centre, has been incorporated into the CT volume of 6 IMRT patients. This was done by CT scanning the tabletop and by adding the obtained volume to the clinical dataset, acquired using the standard couch available in our CT scanner. This procedure was tested and validated for the purpose of this study. The radiotherapy plans have been optimized using both the original CT volume and the modified CT volume. RESULTS: IMRT optimization with the tabletop included in the clinical volume produced significantly different deliverable plans compared to standard optimized plans which did not include the treatment couch. Differences up to 6%/7% in terms of total number of MU were found in half of the clinical cases. Differences up to 37% in the number of MU per beam were also found. The number of iterations needed to reach an optimal solution also varied between -18% and +25%. Although the DVH analysis produced similar results, due to the fulfilment of the optimization objectives, differences higher than 10% were found in the dose calculated to superficial regions of the body. CONCLUSIONS: The results of this investigation show that the presence of the carbon fibre tabletop significantly affects the outcome of the beam parameters optimization. We suggest including carbon fibre tabletops into patient treatment planning dose calculation and optimization.

A case of tumor of the penis: interstitial brachitherapy after conservative surgical therapy.

The neoplasms of the penis are extremely rare and have an incidence of 1400 new cases for year in the United States. Higher is the percentage of incidence in Africa and Asia (10-20%) and in some areas of Brasil where the cancer of the penis constitutes 17% of all the male tumors. In Israel this neoplasm is rare, less than 0.1/100000 menfor year, because in Jewish population men are circumcised prematurely. Recently it has been placed attention to the possible aetiologic role of human papillomavirus (HPV-16 and HPV-18) in penis carcinoma. In fact, in the tumoral cells, DNA of this virus has been found with a percentage that varies from the 30 to 82%. Traditional surgical approach is total or partial penis resection basing on the extension of the disease. This procedure is associated to remarkable psycosessuals problems that greatly affect the quality of life. We bring back a case with organ sparing conservative treatment.