Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer.

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

Stomach and duodenum dose-volume constraints for locally advanced pancreatic cancer patients treated in 15 fractions in combination with chemotherapy.

Purpose: To assess dosimetry predictors of gastric and duodenal toxicities for locally advanced pancreatic cancer (LAPC) patients treated with chemo-radiotherapy in 15 fractions. Methods: Data from 204 LAPC patients treated with induction+concurrent chemotherapy and radiotherapy (44.25 Gy in 15 fractions) were available. Forty-three patients received a simultaneous integrated boost of 48-58 Gy. Gastric/duodenal Common Terminology Criteria for Adverse Events v. 5 (CTCAEv5) Grade ≥2 toxicities were analyzed. Absolute/% duodenal and stomach dose-volume histograms (DVHs) of patients with/without toxicities were compared: the most predictive DVH points were identified, and their association with toxicity was tested in univariate and multivariate logistic regressions together with near-maximum dose (D0.03) and selected clinical variables. Results: Toxicity occurred in 18 patients: 3 duodenal (ulcer and duodenitis) and 10 gastric (ulcer and stomatitis); 5/18 experienced both. At univariate analysis, V44cc (duodenum: p = 0.02, OR = 1.07; stomach: p = 0.01, OR = 1.12) and D0.03 (p = 0.07, OR = 1.19; p = 0.008, OR = 1.12) were found to be the most predictive parameters. Stomach/duodenum V44Gy and stomach D0.03 were confirmed at multivariate analysis and found to be sufficiently robust at internal, bootstrap-based validation; the results regarding duodenum D0.03 were less robust. No clinical variables or %DVH was significantly associated with toxicity. The best duodenum cutoff values were V44Gy < 9.1 cc (and D0.03 < 47.6 Gy); concerning the stomach, they were V44Gy < 2 cc and D0.03 < 45 Gy. The identified predictors showed a high negative predictive value (>94%). Conclusion: In a large cohort treated with hypofractionated radiotherapy for LAPC, the risk of duodenal/gastric toxicities was associated with duodenum/stomach DVH. Constraining duodenum V44Gy < 9.1 cc, stomach V44Gy < 2 cc, and stomach D0.03 < 45 Gy should keep the toxicity rate at approximately or below 5%. The association with duodenum D0.03 was not sufficiently robust due to the limited number of events, although results suggest that a limit of 45-46 Gy should be safe.

iTIND for BPH: Technique and procedural outcomes: A narrative review of current literature.

In the last few years, new technologies have been developed to treat benign prostatic hyperplasia (BPH) in order to offer valid surgical alternatives to transurethral resection of the prostate with lower complications and hospitalization while maintaining satisfactory functional results. Among these new approaches, transurethral implantation of first- and second-generation temporary implantable nitinol device (TIND and iTIND, respectively) (Medi-TateVR ; Medi-Tate Ltd., Or Akiva, Israel) has been proposed. The aim of this work is to describe the surgical technique and to perform a systematic review of the available literature on follow-up of functional outcomes. A systematic research of the available literature on this topic was performed via Medline, Embase, and Cochrane databases in April 2021. Current evidence regarding the implantation of iTIND to treat BPH-related lower urinary tract symptoms (LUTSs) is still limited. Seven studies have been found. Only one randomized controlled trial has been published reporting short-term follow-up of implantation of iTIND versus sham procedure. All the studies reported that both procedures are safe, effective, and well-tolerated. Moreover, such treatment seems to not affect patient's sexual and ejaculatory functions. In conclusions, current clinical evidence suggests that temporary implantation of iTIND is a valid option for the minimally invasive surgical treatment of BPH-related LUTS. Further studies are required in order to confirm the functional results, especially over a long-term follow-up.

Clinical Implementation of Knowledge-Based Automatic Plan Optimization for Helical Tomotherapy.

PURPOSE: To implement knowledge-based (KB) automatic planning for helical TomoTherapy (HTT). The focus of the first clinical implementation was the case of high-risk prostate cancer, including pelvic node irradiation. METHODS AND MATERIALS: One hundred two HTT clinical plans were selected to train a KB model using the RapidPlan tool incorporated in the Eclipse system (v13.6, Varian Inc). The individually optimized KB-based templates were converted into HTT-like templates and sent automatically to the HTT treatment planning system through scripting. The full dose calculation was set after 300 iterations without any additional planner intervention. Internal (20 patients in the training cohort) and external (28 new patients) validation were performed to assess the performance of the model: Automatic HTT plans (KB-TP) were compared against the original plans (TP) in terms of organs at risk and planning target volume (PTV) dose-volume parameters and by blinded clinical evaluation of 3 expert clinicians. RESULTS: KB-TP plans were generally better than or equivalent to TP plans in both validation cohorts. A significant improvement in PTVs and rectum-PTV overlap dosimetry parameters were observed for both sets. Organ-at-risk sparing for KB-TP was slightly improved, which was more evident in the external validation group and for bladder and bowel. Clinical evaluation reported KB-TP to be better in 60% of cases and worse in 10% compared with TP (P < .05). CONCLUSIONS: The fully KB-based automatic planning workflow was successfully implemented for HTT planning optimization in the case of high-risk patients with prostate cancer.

Impact of sentinel lymph-node biopsy and FDG-PET in staging and radiation treatment of anal cancer patients.

To assess the role of sentinel lymph-node biopsy (SLNB) and FDG-PET in staging and radiation treatment (RT) of anal cancer patients. This retrospective study was performed on 80 patients (male: 32, female: 48) with a median age of 60 years (39-89 years) with anal squamous cell carcinoma who were treated from March 2008 to March 2018 at the IRCCS San Raffaele Hospital. Patients without clinical evidence of inguinal LNs metastases and/or with discordance between clinical evidence and imaging features were considered for SLNB. FDG-PET was performed in 69/80 patients. Patients with negative imaging in inguinal region and negative SLNB could avoid RT on groin to spare inguinal toxicity. CTV included GTV (primary tumour and positive LNs) and pelvic ± inguinal LNs. PTV1 and PTV2 corresponded to GTV and CTV, respectively, adding 0.5 cm. RT dose was 50.4 Gy/28 fractions to PTV2 and 64.8 Gy/36 fractions to PTV1, delivered with 3DCRT (n = 24) or IMRT (n = 56), concomitant to Mitomycin-C and 5-FU chemotherapy. FDG-PET showed inguinal uptake in 21/69 patients (30%) and was negative in 48/69 patients (70%). Lymphoscintigraphy was performed in 11/21 positive patients (4 patients SLNB confirmed inguinal metastases, 6 patients false positive and 1 patient SLN not found), and in 29/48 negative patients (5/29 showed metastases, 23/29 true negative and 1 SLN not found). Sensitivity, specificity, positive and negative predictive value of FDG-PET were 62%, 79%, 40% and 82%, respectively. Median follow-up time from diagnosis was 40.3 months (range: 4.6-136.4 months): 69 patients (86%) showed a complete response, 10 patients (13%) a partial response, 1 patient (1%) a stable disease. Patients treated on groin (n = 54) versus not treated (n = 26) showed more inguinal dermatitis (G1-G2: 50% vs. 12%; G3-G4: 17% vs. 0%, p < 0.05). For patients treated on groin, G3-G4 inguinal dermatitis, stomatitis and neutropenia were significantly reduced with IMRT against 3DCRT techniques (13% vs. 36%, p = 0.10; 3% vs. 36%, p = 0.003; 8% vs. 29%, p = 0.02, respectively). SLNB improves the FDG-PET inguinal LNs staging in guiding the decision to treat inguinal nodes. IMRT technique significantly reduced G3-G4 toxicities when patients are treated on groin.

Robustness of CT radiomic features against image discretization and interpolation in characterizing pancreatic neuroendocrine neoplasms.

PURPOSE: To explore the variation of the discriminative power of CT radiomic features (RF) against image discretization/interpolation in characterizing pancreatic neuro-endocrine (PanNEN) neoplasms. MATERIALS AND METHODS: Thirty-nine PanNEN patients with pre-surgical high contrast CT available were considered. Image interpolation and discretization parameters were intentionally changed, including pixel size (0.73-2.19 mm2), slice thickness (2-5 mm) and binning (32-128 grey levels) and their combination generated 27 parameter's set. The ability of 69 RF in discriminating post-surgically assessed tumor grade (>G1), positive nodes, metastases and vascular invasion was tested: AUC changes when changing the parameters were quantified for selected RF, significantly associated to each end-point. The analysis was repeated for the corresponding images with contrast medium and in a sub-group of 29/39 patients scanned on a single scanner. RESULTS: The median tumor volume was 1.57 cm3 (16%-84% percentiles: 0.62-34.58 cm3). RF variability against discretization/interpolation parameters was large: only 21/69 RF showed %COV < 20%. Despite this variability, AUC changes were limited for all end-points: with typical AUC values around 0.75-0.85, AUC ranges for the 27 parameter's set were on average 0.062 (1SD:0.037) for all end-points with maximum %COV equal to 5.5% (mean:2.3%). Performances significantly improved when excluding the 5 mm thickness case and fixing the binning to 64 (mean AUC range: 0.036, 1SD:0.019). Using contrast images or limiting the population to single-scanner patients had limited impact on AUC variability. CONCLUSIONS: The discriminative power of CT RF for panNEN is relatively invariant against image interpolation/discretization within a large range of voxel sizes and binning.

All you need to know about "Aquablation" procedure for treatment of benign prostatic obstruction.

INTRODUCTION: In recent years, technological advances and new approaches have been developed for the treatment of benign prostatic obstruction (BPO) in order to reduce complications like bleeding, retrograde ejaculation and risk of infection while obtaining an adequate disobstruction. The most recent surgical approach introduced is the Aquablation system (PROCEPT BioRobotics, Redwood Shores, CA, USA). This intervention is a robotically guided system that uses high-velocity water jets in order to ablate prostatic tissue, with real-time ultrasound guidance. The aim of this review is to summarize the current evidence on Aquablation and its results, compared to the reported outcomes of the gold standard treatment, the transurethral resection of the prostate (TURP). EVIDENCE ACQUISITION: A systematic review of the Literature was performed in June 2019 using Medline (via PubMed), Embase (via Ovid), and Cochrane databases. The studies that compared the Aquablation to the standard TURP were included. Moreover, a critical review of the single arm studies was conducted. EVIDENCE SYNTHESIS: The results of this systematic review, based on a single RCT that compared Aquablation vs. TURP in prostates 30-80 cc in size, confirmed that Aquablation has at least a similar efficacy as TURP, but has a better safety profile, allows shorter resection times, and has a lower risk of retrograde ejaculation. Moreover, in some subcategories of patients (e.g., when prostate volume is >50 cc) functional outcomes of Aquablation are better than those of TURP. Evidence from non-comparative clinical studies and from real life scenarios have confirmed that Aquablation may be used effectively for prostate volumes up to 150 cc. CONCLUSIONS: The Aquablation procedure for the treatment of BPO allows high clinical efficacy with an excellent safety profile. For prostate volume 30-80 cc, comparative studies demonstrated that this procedure offers clinical results at least comparable to those of conventional TURP. Latest evidence showed that Aquablation may be used effectively for prostate volumes up to 150 cc. The major strengths are its high-speed resection time, low complication rate, and potential for sexual function preservation.

Knowledge-based automatic optimization of adaptive early-regression-guided VMAT for rectal cancer.

PURPOSE: To implement a knowledge-based (KB) optimization strategy to our adaptive (ART) early-regression guided boosting technique in neo-adjuvant radio-chemotherapy for rectal cancer. MATERIAL AND METHODS: The protocol consists of a first phase delivering 27.6 Gy to tumor/lymph-nodes (2.3 Gy/fr-PTV1), followed by the ART phase concomitantly delivering 18.6 Gy (3.1 Gy/fr) and 13.8 Gy (2.3 Gy/fr) to the residual tumor (PTVART) and to PTV1 respectively. PTVART is obtained by expanding the residual GTV, as visible on MRI at fraction 9. Forty plans were used to generate a KB-model for the first phase using the RapidPlan tool. Instead of building a new model, a robust strategy scaling the KB-model to the ART phase was applied. Both internal and external validation were performed for both phases: all automatic plans (RP) were compared in terms of OARs/PTVs parameters against the original plans (RA). RESULTS: The resulting automatic plans were generally better than or equivalent to clinical plans. Of note, V30Gy and V40Gy were significantly improved in RP plans for bladder and bowel; gEUD analysis showed improvement for KB-modality for all OARs, up to 3 Gy for the bowel. CONCLUSIONS: The KB-model generated for the first phase was robust and it was also efficiently adapted to the ART phase. The performance of automatically generated plans were slightly better than the corresponding manual plans for both phases.

3D imaging applications for robotic urologic surgery: an ESUT YAUWP review.

CONTEXT: Despite the current era of precision surgery in robotics, an unmet need still remains for optimal surgical planning and navigation for most genitourinary diseases. 3D virtual reconstruction of 2D cross-sectional imaging has been increasingly adopted to help surgeons better understand the surgical anatomy. OBJECTIVES: To provide a short overview of the most recent evidence on current applications of 3D imaging in robotic urologic surgery. EVIDENCE ACQUISITION: A non-systematic review of the literature was performed. Medline, PubMed, the Cochrane Database and Embase were screened for studies regarding the use of 3D models in robotic urology. EVIDENCE SYNTHESIS: 3D reconstruction technology creates 3D virtual and printed models that first appeared in urology to aid surgical planning and intraoperative navigation, especially in the treatment of oncological diseases of the prostate and kidneys. The latest revolution in the field involves models overlapping onto the real anatomy and performing augmented reality procedures. CONCLUSION: 3D virtual/printing technology has entered daily practice in some tertiary centres, especially for the management of urological tumours. The 3D models can be virtual or printed, and can help the surgeon in surgical planning, physician education and training, and patient counselling. Moreover, integration of robotic platforms with the 3D models and the possibility of performing augmented reality surgeries increase the surgeon's confidence with the pathology, with potential benefits in precision and tailoring of the procedures.

Risk of Gleason Score 3+4=7 prostate cancer upgrading at radical prostatectomy is significantly reduced by targeted versus standard biopsy.

BACKGROUND: The aim of this study is to evaluate if multiparametric magnetic resonance (mpMRI)-transrectal ultrasound (TRUS) fusion targeted biopsy (TBx) versus untargeted standard biopsy (SBx) may decrease the rate of pathological upgrading of Gleason Score (GS) 3+4 prostate cancer (PCa) at radical prostatectomy (RP). We also evaluated the impact of percent pattern 4 and cribriform glands at biopsy in the risk of GS 3+4=7 upgrading. METHODS: A total of 301 patients with GS 3+4 PCa on biopsy (159 SBx and 142 TBx) who underwent laparoscopic robot-assisted RP were sequentially enrolled. Histological data from RP sections were used as reference standard. The concordance of biopsy with pathological GS, as well as the GS 3+4 upgrading at RP were evaluated in different univariate and multivariate binary logistic regression models, testing age, PSA, fPSA%, tumor volume, PI-RADS, clinical stage, percentage of Gleason pattern 4 (GP) and/or presence of cribriform sub-type at biopsy. RESULTS: Of the 301 biopsies, the median of GP 4 was 16% of the tissue. Minimal GP 4 (≤16%) cancers had a significant lower median volume (1.7 mL) than those with GP4 >16% (2.9 mL), (P<0.001). Pathological GS 3+4 was confirmed for 58.8% and 82.2% for SBx and TBx patients, respectively. The rate of upgraded and downgraded GS on SBx versus TBx was 38.8% vis. 16.7% and 1.8% and 2.1%, respectively. The rate of upgrading was significantly associated with the presence of GP4 >16% versus ≤16% (OR 4.4, 95% CI 1.4-12.0; P=0.021) and with the presence of cribriform sub-type at biopsy specimens (OR 6.2, 95% CI 2.2-18.7; P<0.001). CONCLUSIONS: We demonstrated that TBx technique significantly reduced the risk of GS 3+4 upgrading at RP, compared to SBx one. The rate of upgrading was significantly associated with GP4>16%, mostly when cribriform sub-type was present at biopsy specimens.

Monitoring skin dose changes during image-guided helical tomotherapy for head and neck cancer patients.

PURPOSE: An increase of skin dose during head and neck cancer (HNC) radiotherapy is potentially dangerous. Aim of this study was to quantify skin dose variation and to assess the need of planning adaptation (ART) to counteract it. METHODS: Planning CTs of 32 patients treated with helical tomotherapy (HT) according to a Simultaneous Integrated Boost (SIB) technique delivering 54/66 Gy in 30 fractions were deformably co-registered to MVCTs taken at fractions 15 and 30; in addition, the first fraction was also considered. The delivered dose-of-the-day was calculated on the corresponding deformed images. Superficial body layers (SL) were considered as a surrogate for skin, considering a layer thickness of 2 mm. Variations of SL DVH (∆SL) during therapy were quantified, focusing on ∆SL95% (i.e., 62.7 Gy). RESULTS: Small changes (within ± 1 cc for ∆SL95%) were seen in 15/32 patients. Only 2 patients experienced ∆SL95% > 1 cc in at least one of the two monitored fractions. Negative ∆SL95% > 1 cc (up to 17 cc) were much more common (15/32 patients). The trend of skin dose changes was mostly detected at the first fraction. Negative changes were correlated with the presence of any overlap between PTV and SL at planning and were explained in terms of how the planning system optimizes the PTV dose coverage near the skin. Acute toxicity was associated with planning DVH and this association was not improved if considering DVHs referring to fractions 15/30. CONCLUSION: About half of the patients treated with SIB with HT for HNC experienced a skin-sparing effect during therapy; only 6% experienced an increase. Our findings do not support skin-sparing ART, while suggesting the introduction of improved skin-sparing planning techniques.

Adrenal tumours: open surgery versus minimally invasive surgery.

PURPOSE OF REVIEW: The aim of this article is to focus on state-of-the-art minimally invasive adrenalectomy (MIA) and the most recent role of open adrenalectomy for adrenal tumours, respect to MIA and open adrenalectomy for adrenocortical cancer (ACC). RECENT FINDINGS: The laparoscopic (both transperitoneal and retroperitoneal) approach is the first-choice treatment in cases of small-to-medium benign adrenal tumours. This approach is feasible and well tolerated even for larger lesions without radiological signs of malignancy. Robotic adrenalectomy has recently increased in popularity, although the results appear to be fully comparable with those of laparoscopy. Open approach is the keystone of ACC surgery, especially when neighbour tissues, organs, or vessels are involved. Recent evidence suggests caution in treating localized ACC with laparoscopy, because of the higher rate of local or peritoneal recurrence, and shorter recurrence-free survival rates with respect to open adrenalectomy. SUMMARY: MIA has progressively replaced the traditional open approach and plays a complementary role in the treatment of adrenal tumour. It is the first option for benign lesions, whereas open adrenalectomy is a cornerstone treatment for ACC. The overlap of indications for laparoscopic adrenalectomy and open adrenalectomy is today confined to the treatment of organ-confined adrenal cancer, in which the role of laparoscopic surgery is far from being clearly defined.

Accurate outcome prediction after neo-adjuvant radio-chemotherapy for rectal cancer based on a TCP-based early regression index.

BACKGROUND AND PURPOSE: An early tumor regression index (ERITCP) was previously introduced and found to predict pathological response after neo-adjuvant radio-chemotherapy of rectal cancer. ERITCP was tested as a potential biomarker in predicting long-term disease-free survival. MATERIALS AND METHODS: Data of 65 patients treated with an early regression-guided adaptive boosting technique (ART) were available. Overall, loco-regional relapse-free and distant metastasis-free survival (OS, LRFS, DMFS) were considered. Patients received 41.4 Gy in 18 fractions (2.3 Gy/fr), including ART concomitant boost on the residual GTV during the last 6 fractions (3 Gy/fr, Dmean: 45.6 Gy). Chemotherapy included oxaliplatin and 5-fluorouracil (5-FU). T2-weighted MRI taken before (MRIpre) and at half therapy (MRIhalf) were available and GTVs were contoured (Vpre, Vhalf). The parameter ERITCP = -ln[(1 - (Vhalf/Vpre))Vpre] was calculated for all patients. Cox regression models were assessed considering several clinical and histological variables. Cox models not including/including ERITCP (CONV_model and REGR_model respectively) were assessed and their discriminative power compared. RESULTS: At a median follow-up of 47 months, OS, LRFS and DMFS were 94%, 95% and 78%. Due to too few events, multivariable analyses focused on DMFS: the resulting CONV_model included pathological complete remission or clinical complete remission followed by surgery refusal (HR: 0.15, p = 0.07) and 5-FU dose >90% (HR: 0.29, p = 0.03) as best predictors, with AUC = 0.75. REGR_model included ERITCP (HR: 1.019, p < 0.0001) and 5-FU dose >90% (HR: 0.18, p = 0.005); AUC was 0.86, significantly higher than CONV_model (p = 0.05). Stratifying patients according to the best cut-off value for ERITCP and to 5-FU dose (> vs <90%) resulted in 47-month DMFS equal to 100%/69%/0% for patients with two/one/zero positive factors respectively (p = 0.0002). ERITCP was also the only variable significantly associated to OS (p = 0.01) and LRFS (p = 0.03). CONCLUSION: ERITCP predicts long-term DMFS after radio-chemotherapy for rectal cancer: an independent impact of the 5-FU dose was also found. This result represents a first step toward application of ERITCP in treatment personalization: additional confirmation on independent cohorts is warranted.

Ct radiomic features of pancreatic neuroendocrine neoplasms (panNEN) are robust against delineation uncertainty.

PURPOSE: The aim of this study was to quantify the impact of CT delineation uncertainty of pancreatic neuroendocrine neoplasms (panNEN) on Radiomic features (RF). METHODS: Thirty-one previously operated patients were considered. Three expert radiologists contoured panNEN lesions on pre-surgical high-resolution contrast-enhanced CT images and contours were transferred onto pre-contrast CT. Volume agreement was quantified by the DICE index. After images resampling and re-binning, 69 RF were extracted and the impact of inter-observer variability was assessed by Intra-Class Correlation (ICC): ICC > 0.80 was considered as a threshold for "very high" inter-observer agreement. RESULTS: The median volume was 1.3 cc (range: 0.2-110 cc); a satisfactory inter-observer volume agreement was found (mean DICE = 0.78). Only 4 RF showed ICC < 0.80 (0.48-0.73), including asphericity and three RFs (of five) of the neighborhood intensity difference matrix (NID). CONCLUSIONS: The impact of inter-observer variability in delineating panNEN on RF was minimum, with the exception of the NID family and asphericity, showing a moderate agreement. These results support the feasibility of studies aiming to assess CT radiomic biomarkers for panNEN.

A TCP-based early regression index predicts the pathological response in neo-adjuvant radio-chemotherapy of rectal cancer.

PURPOSE: Introducing a radiobiological index based on early tumor regression during neo-adjuvant radio-chemotherapy (RCT, including oxaliplatin) of rectal adenocarcinoma and testing its discriminative power in predicting the tumor response. METHODS: Seventy-four patients were treated with Helical Tomotherapy following an adaptive (ART) protocol (41.4 Gy/18 fr, 2.3 Gy/fr) delivering a simultaneous integrated boost on the residual tumor in the last 6 fractions up to 45.6 Gy. T2-weighted MRI were taken before (MRIpre) and at mid (MRImid) therapy and the corresponding tumor volumes were considered (Vpre,Vmid). The "Early Regression Index" [Formula: see text] was introduced and its discriminative power was assessed in terms of AUC, sensitivity/specificity, positive/negative predictive value (PPV/NPV). Two end-points were considered: (a) pathological complete response (pCR) or clinical complete response followed by watch-and-wait, (cCR); (b) limited response (residual vital cells (RVC) in the surgical specimen >10%). RESULTS: Complete data were available for 65 patients: pCR, cCR and RVC >10% were 20, 2 and 19 respectively. The discriminative power of ERITCP was moderately high (AUC = 0.81/0.75 for /pCRorcCR/RVC >10% respectively, p < 0.0005). ERITCP was highly sensitive (86-89%) with very high NPV (90-94%). The discriminative power of ERITCP was confirmed on a subgroup of 44/65 patients when considering tumor volumes delineated by a skilled radiologist. CONCLUSION: A radiobiologically consistent index based on early regression showed high performances in predicting the pathological response after neo-adjuvant RCT for rectal cancer with relevant potentialities for ART/treatment customization.

Quantifying the robustness of [18F]FDG-PET/CT radiomic features with respect to tumor delineation in head and neck and pancreatic cancer patients.

PURPOSE: To investigate the robustness of PET radiomic features (RF) against tumour delineation uncertainty in two clinically relevant situations. METHODS: Twenty-five head-and-neck (HN) and 25 pancreatic cancer patients previously treated with 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)-based planning optimization were considered. Seven FDG-based contours were delineated for tumour (T) and positive lymph nodes (N, for HN patients only) following manual (2 observers), semi-automatic (based on SUV maximum gradient: PET_Edge) and automatic (40%, 50%, 60%, 70% SUV_max thresholds) methods. Seventy-three RF (14 of first order and 59 of higher order) were extracted using the CGITA software (v.1.4). The impact of delineation on volume agreement and RF was assessed by DICE and Intra-class Correlation Coefficients (ICC). RESULTS: A large disagreement between manual and SUV_max method was found for thresholds  ≥50%. Inter-observer variability showed median DICE values between 0.81 (HN-T) and 0.73 (pancreas). Volumes defined by PET_Edge were better consistent with the manual ones compared to SUV40%. Regarding RF, 19%/19%/47% of the features showed ICC < 0.80 between observers for HN-N/HN-T/pancreas, mostly in the Voxel-alignment matrix and in the intensity-size zone matrix families. RFs with ICC < 0.80 against manual delineation (taking the worst value) increased to 44%/36%/61% for PET_Edge and to 69%/53%/75% for SUV40%. CONCLUSIONS: About 80%/50% of 72 RF were consistent between observers for HN/pancreas patients. PET_edge was sufficiently robust against manual delineation while SUV40% showed a worse performance. This result suggests the possibility to replace manual with semi-automatic delineation of HN and pancreas tumours in studies including PET radiomic analyses.

3-Year follow-up of temporary implantable nitinol device implantation for the treatment of benign prostatic obstruction.

OBJECTIVES: To report 3-year follow-up results of the first implantations with a temporary implantable nitinol device (TIND® ; Medi-Tate Ltd., Or Akiva, Israel) for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In all, 32 patients with LUTS were enrolled in this prospective study. The study was approved by the local Ethics Committee. Inclusion criteria were: age >50 years, International Prostate Symptom Score (IPSS) ≥10, peak urinary flow (Qmax ) <12 mL/s, and prostate volume <60 mL. The TIND was implanted within the bladder neck and the prostatic urethra under light sedation, and removed 5 days later in an outpatient setting. Demographics, perioperative results, complications (according to Clavien-Dindo classification), functional results, and quality of life (QoL) were evaluated. Follow-up assessments were made at 3 and 6 weeks, and 3, 6, 12, 24 and 36 months after the implantation. The Student's t-test, one-way analysis of variance and Kruskal-Wallis tests were used for statistical analyses. RESULTS: At baseline, the mean (standard deviation, sd) patient age was 69.4 (8.2) years, prostate volume was 29.5 (7.4) mL, and Qmax was 7.6 (2.2) mL/s. The median (interquartile range, IQR) IPSS was 19 (14-23) and the QoL score was 3 (3-4). All the implantations were successful, with a mean total operative time of 5.8 min. No intraoperative complications were recorded. The change from baseline in IPSS, QoL score and Qmax was significant at every follow-up time point. After 36 months of follow-up, a 41% rise in Qmax was achieved (mean 10.1 mL/s), the median (IQR) IPSS was 12 (6-24) and the IPSS QoL was 2 (1-4). Four early complications (12.5%) were recorded, including one case of urinary retention (3.1%), one case of transient incontinence due to device displacement (3.1%), and two cases of infection (6.2%). No further complications were recorded during the 36-month follow-up. CONCLUSIONS: The extended follow-up period corroborated our previous findings and suggests that TIND implantation is safe, effective and well-tolerated, for at least 36 months after treatment.

Skin dose calculation during radiotherapy of head and neck cancer using deformable image registration of planning and mega-voltage computed tomography scans.

BACKGROUND AND PURPOSE: Head-Neck (HN) patients may experience severe acute skin complications that can cause treatment interruption and increase the risk of late fibrosis. This study assessed a method for accurately monitoring skin dose changes during helical tomotherapy for HN cancer based on deformable image registration of planning computed tomography (CT) and mega-voltage CT (MVCT). MATERIALS AND METHODS: Planning CTs of nine patients were deformably registered to mid-treatment MVCT (MV15) images resulting in CTdef images. The original plans were recalculated on both CTdef and mid-treatment kilo-voltage CT (CT15) taken as ground truth. Superficial layers (SL) of the body with thicknesses of 2, 3 and 5 mm (SL2, SL3, SL5) were considered as derma surrogates. SL V95%, V97%, V98%, V100%, V102%, V105% and V107% of the prescribed PTV dose were extracted for CT15/CTdef and compared (considering patients with skin dose > 95%). For comparison, doses were calculated directly on the calibrated MVCT and analyzed in the same way. RESULTS: Differences between SL2/SL3/SL5 V95%-V107% in CT15/CTdef were very small: for eight of nine patients the difference between the considered SL2 Vd% computed on CTdef and CT15 was less than 1.4 cm3 for all d%. A larger value was found when using MVCT for skin dose calculation (4.8 cm3 for SL2), although CTdef body contour matched CT15 body with accuracy similar to that of MV15. CONCLUSIONS: Deforming the planning CT-to-MVCT was shown to be accurate considering external body contours and skin DVHs. The method was able to accurately identify superficial overdosing.

Robot-assisted laparoendoscopic single-site versus mini-laparoscopic pyeloplasty: a comparison of perioperative, functional and cosmetic results.

BACKGROUND: New approaches have been developed to further reduce the invasiveness of laparoscopic pyeloplasty (P) as treatment for uretero-pelvic junction obstruction (UPJO). Aim of the study was to compare perioperative, functional and cosmetic results of mini-laparoscopic (mL-P) versus robot-assisted laparoendoscopic single-site P (rLESS-P). METHODS: Since April 2009 to June 2010, 12 adult patients with primary UPJO, BMI<25 and no previous abdominal surgeries were enrolled undergoing mLP (3-mm instruments only). With the same indications since February 2012 to October 2013, 15 patients underwent rLESS-P with "single site"® platform (Intuitive Surgery Inc, Sunnyvale, CA, USA). Success of surgeries was determined by clinical parameters and renal scan (success if T 1/2<20 min) at 12 months postoperatively. Demographics and perioperative results were analyzed. Cosmetic results were assessed by using the Patient Scar Assessment Questionnaire (PSAQ). RESULTS: Groups were comparable at baseline. No differences were found in perioperative variables except for a longer operative time in rLESS-P group (128 vs. 190, P<0.001). Postoperative complications rate, analgesic consumption, pain visual analogue scale scores, hospital stay and success rate of surgeries were not significantly different between the groups. PSAQ revealed that in both the groups patients were satisfied with the cosmetic result. At one-year follow-up no recurrences were observed. Semiquantitative analysis of costs revealed an extra-cost for rLESS-P of € 3410 per procedure. CONCLUSIONS: In our experience, both mLP and rLESS-P appeared to be feasible and safe in the treatment of UPJO and allowed for excellent cosmetic results. r-LESS required longer operative times and higher costs.

Early prediction of radiotherapy-induced parotid shrinkage and toxicity based on CT radiomics and fuzzy classification.

MOTIVATION: Patients under radiotherapy for head-and-neck cancer often suffer of long-term xerostomia, and/or consistent shrinkage of parotid glands. In order to avoid these drawbacks, adaptive therapy can be planned for patients at risk, if the prediction is obtained timely, before or during the early phase of treatment. Artificial intelligence can address the problem, by learning from examples and building classification models. In particular, fuzzy logic has shown its suitability for medical applications, in order to manage uncertain data, and to build transparent rule-based classifiers. In previous works, clinical, dosimetric and image-based features were considered separately, to find different possible predictors of parotid shrinkage. On the other hand, a few works reported possible image-based predictors of xerostomia, while the combination of different types of features has been little addressed. OBJECTIVE: This paper proposes the application of a novel machine learning approach, based on both statistics and fuzzy logic, aimed at the classification of patients at risk of i) parotid gland shrinkage and ii) 12-months xerostomia. Both problems are addressed with the aim of individuating predictors and models to classify respective outcomes. METHODS: Knowledge is extracted from a real dataset of radiotherapy patients, by means of a recently developed method named Likelihood-Fuzzy Analysis, based on the representation of statistical information by fuzzy rule-based models. This method enables to manage heterogeneous variables and missing data, and to obtain interpretable fuzzy models presenting good generalization power (thus high performance), and to measure classification confidence. Numerous features are extracted to characterize patients, coming from different sources, i.e. clinical features, dosimetric parameters, and radiomics-based measures obtained by texture analysis of Computed Tomography images. A learning approach based on the composition of simple models in a more complicated one allows to consider the features separately, in order to identify predictors and models to use when only some data source is available, and obtaining more accurate results when more information can be combined. RESULTS: Regarding parotid shrinkage, a number of good predictors is detected, some already known and confirmed here, and some others found here, in particular among radiomics-based features. A number of models are also designed, some using single features and others involving models composition to improve classification accuracy. In particular, the best model to be used at the initial treatment stage, and another one applicable at the half treatment stage are identified. Regarding 12-months toxicity, some possible predictors are detected, in particular among radiomics-based features. Moreover, the relation between final parotid shrinkage rate and 12-months xerostomia is evaluated. The method is compared to the naïve Bayes classifier, which reveals similar results in terms of classification accuracy and best predictors. The interpretable fuzzy rule-based models are explicitly presented, and the dependence between predictors and outcome is explained, thus furnishing in some cases helpful insights about the considered problems. CONCLUSION: Thanks to the performance and interpretability of the fuzzy classification method employed, predictors of both parotid shrinkage and xerostomia are detected, and their influence on each outcome is revealed. Moreover, models for predicting parotid shrinkage at initial and half radiotherapy stages are found.