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Background: High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study is to provide a systematic literature review to compare the toxicity and effectiveness of curative radiotherapy with photon therapy (XRT) or PT in PCa. Methods: PubMed, Embase, and the Cochrane Library databases were systematically searched up to April 2022. Men with a diagnosis of PCa who underwent curative hypofractionated RT treatment (PT or XRT) were included. Risk of grade (G) ≥ 2 acute and late genitourinary (GU) OR gastrointestinal (GI) toxicity were the primary outcomes of interest. Secondary outcomes were five-year biochemical relapse-free survival (b-RFS), clinical relapse-free, distant metastasis-free, and prostate cancer-specific survival. Heterogeneity between study-specific estimates was assessed using Chi-square statistics and measured with the I2 index (heterogeneity measure across studies). Results: A total of 230 studies matched inclusion criteria and, due to overlapped populations, 160 were included in the present analysis. Significant lower rates of G ≥ 2 acute GI incidence (2 % vs 7 %) and improved 5-year biochemical relapse-free survival (95 % vs 91 %) were observed in the PT arm compared to XRT. PT benefits in 5-year biochemical relapse-free survival were maintained for the moderate hypofractionated arm (p-value 0.0122) and among patients in intermediate and low-risk classes (p-values < 0.0001 and 0.0368, respectively). No statistically relevant differences were found for the other considered outcomes. Conclusion: The present study supports that PT is safe and effective for localized PCa treatment, however, more data from RCTs are needed to draw solid evidence in this setting and further effort must be made to identify the patient subgroups that could benefit the most from PT.

Cognitive dysfunctions and functional brain modifications are among the side effects reported by breast cancer patients that persist beyond the chemotherapy. This paper aims at synthesizing the evidence on cognitive and functional brain changes and their associations in breast cancer patients treated with chemotherapy. A systematic literature search was performed using PubMed, Ovid MEDLINE, Scopus, and Embase up to July 2022. Eligible studies evaluated adult women with breast cancer treated with systemic chemotherapy, that performed cognitive assessment and resting-state functional MRI. Methodological quality was assessed. Sixteen studies were included, with a total of 1054 female participants. All studies reported alterations mainly concerned the fronto-parieto-temporal system and specifically involved the disruption of the DMN. Consistent with these findings, BCPs showed changes in cognitive performance reporting dysfunctions in executive ability, memory, and attention. However, not all the studies found a significant association between functional brain alterations and cognitive dysfunction. Some limitations including lack of sample homogeneity and different methodological approaches were reported. This work highlighted the presence of cognitive dysfunctions and functional brain alteration in breast cancer patients treated with chemotherapy. This allows a greater awareness of the side effects, promoting better clinical management. However, further research is needed to investigate the cause-effect relationship between cognitive and functional alterations.

High- and low-risk endometrial carcinoma (EC) differ in whether or not a lymphadenectomy is performed. We aimed to develop MRI-based radio-genomic models able to preoperatively assess lymph-vascular space invasion (LVSI) and discriminate between low- and high-risk EC according to the ESMO-ESGO-ESTRO 2020 guidelines, which include molecular risk classification proposed by “ProMisE”. This is a retrospective, multicentric study that included 64 women with EC who underwent 3T-MRI before a hysterectomy. Radiomics features were extracted from T2WI images and apparent diffusion coefficient maps (ADC) after manual segmentation of the gross tumor volume. We constructed a multiple logistic regression approach from the most relevant radiomic features to distinguish between low- and high-risk classes under the ESMO-ESGO-ESTRO 2020 guidelines. A similar approach was taken to assess LVSI. Model diagnostic performance was assessed via ROC curves, accuracy, sensitivity and specificity on training and test sets. The LVSI predictive model used a single feature from ADC as a predictor; the risk class model used two features as predictors from both ADC and T2WI. The low-risk predictive model showed an AUC of 0.74 with an accuracy, sensitivity, and specificity of 0.74, 0.76, 0.94; the LVSI model showed an AUC of 0.59 with an accuracy, sensitivity, and specificity of 0.60, 0.50, 0.61. MRI-based radio-genomic models are useful for preoperative EC risk stratification and may facilitate therapeutic management.

Purpose: To develop a novel risk tool that allows the prediction of lymph node invasion (LNI) among patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND). Methods: We retrospectively identified 742 patients treated with RARP + ePLND at a single center between 2012 and 2018. All patients underwent multiparametric magnetic resonance imaging (mpMRI) and were diagnosed with targeted biopsies. First, the nomogram published by Briganti et al. was validated in our cohort. Second, three novel multivariable logistic regression models predicting LNI were developed: (1) a complete model fitted with PSA, ISUP grade groups, percentage of positive cores (PCP), extracapsular extension (ECE), and Prostate Imaging Reporting and Data System (PI-RADS) score; (2) a simplified model where ECE score was not included (model 1); and (3) a simplified model where PI-RADS score was not included (model 2). The predictive accuracy of the models was assessed with the receiver operating characteristic-derived area under the curve (AUC). Calibration plots and decision curve analyses were used. Results: Overall, 149 patients (20%) had LNI. In multivariable logistic regression models, PSA (OR: 1.03; P= 0.001), ISUP grade groups (OR: 1.33; P= 0.001), PCP (OR: 1.01; P= 0.01), and ECE score (ECE 4 vs. 3 OR: 2.99; ECE 5 vs. 3 OR: 6.97; P< 0.001) were associated with higher rates of LNI. The AUC of the Briganti et al. model was 74%. Conversely, the AUC of model 1 vs. model 2 vs. complete model was, respectively, 78% vs. 81% vs. 81%. Simplified model 1 (ECE score only) was then chosen as the best performing model. A nomogram to calculate the individual probability of LNI, based on model 1 was created. Setting our cut-off at 5% we missed only 2.6% of LNI patients. Conclusions: We developed a novel nomogram that combines PSA, ISUP grade groups, PCP, and mpMRI-derived ECE score to predict the probability of LNI at fin

Aim: The primary aim of this study is to provide preliminary indications for safe constraints of rectum and bladder in patients re-irradiated with stereotactic body RT (SBRT). Methods: Data from patients treated for prostate cancer (PCa) and intraprostatic relapse, from 1998 to 2016, were retrospectively collected. First RT course was delivered with 3D conformal RT techniques, SBRT or volumetric modulated arc therapy (VMAT). All patients underwent re-irradiation with SBRT with heavy hypofractionated schedules. Cumulative dose-volume values to organs at risk (OARs) were computed and possible correlation with developed toxicities was investigated. Results: Twenty-six patients were included. Median age at re-irradiation was 75 years, mean interval between the two RT courses was 5.6 years and the median follow-up was 47.7 months (13.4–114.3 months). After re-irradiation, acute and late G ≥ 2 GU toxicity events were reported in 3 (12%) and 10 (38%) patients, respectively, while late G ≥ 2 GI events were reported in 4 (15%) patients. No acute G ≥ 2 GI side effects were registered. Patients receiving an equivalent uniform dose of the two RT treatments < 131 Gy appeared to be at higher risk of progression (4-yr b-PFS: 19% vs 33%, p = 0.145). Cumulative re-irradiation constraints that appear to be safe are D30% < 57.9 Gy for bladder and D30% < 66.0 Gy, D60% < 38.0 Gy and V122.1 Gy < 5% for rectum. Conclusion: Preliminary re-irradiation constraints for bladder and rectum have been reported. Our preliminary investigation may serve to clear some grey areas of PCa re-irradiation.

Objectives: To develop a novel nomogram to identify candidates for active surveillance (AS) that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings; and to compare its predictive accuracy to, respectively: (i) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, (ii) Johns Hopkins (JH) criteria, (iii) European Association of Urology (EAU) low-risk classification, and (iv) EAU low-risk or low-volume with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 classification. Patients and Methods: We selected 1837 patients with ISUP GG1 or GG2 prostate cancer (PCa), treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (i.e., clinically significant PCa [csPCa]) at RP, defined as: ISUP GG (Formula presented.) 3 and/or pathological T stage (pT) ≥3a and/or pathological N stage (pN) 1. First, logistic regression models including PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 binary classifications (not eligible vs eligible) were used. Second, a multivariable logistic regression model including age, prostate-specific antigen density (PSA-D), ISUP GG, and the percentage of positive cores (Model 1) was fitted. Third, Prostate Imaging-Reporting and Data System (PI-RADS) score (Model 2), extracapsular extension (ECE) score (Model 3) and PI-RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses were used. Results: Of the 1837 patients, 775 (42.2%) had csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%), and 209 (11.4%) patients were eligible for AS according to, respectively, the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS, and JH criteria. The proportion of csPCa amongst the E

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Context: The optimal management of oligometastatic prostate cancer (PCa) is still debated. Objective: The purpose of the present systematic review and meta-analysis is to collect the available evidence to date to better define the role of stereotactic body radiotherapy (SBRT) in selected patients with oligorecurrent PCa. Evidence acquisition: Study methodology complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). All prospective studies including PCa patients with nodal and/or bone oligometastases (one to five lesions) were considered eligible. Heterogeneity between study-specific estimates was tested using chi-square statistics and measured with the I2 index. A pooled estimate was obtained by fitting both fixed-effect and DerSimonian and Laird random-effect model. Evidence synthesis: Overall, six works (two randomized and the remainder observational) published between 2013 and 2020 were considered eligible. Globally, data from 445 patients were incorporated, of whom 396 were treated with SBRT (329 in observational studies and the remaining 67 in randomized ones). Regarding local progression-free survival (PFS), five studies reported values close to 100%, while one reported a value of 80% in the observation arm. The benefit in terms of biochemical PFS brought by SBRT was evident in all considered studies. Such a difference in cumulative probabilities between the intervention arm and the comparator arm is maintained even 24 mo after the baseline. All studies but one considered toxicity among the endpoints of interest. Most events were classified as either G1 or G2, and the only G ≥ 3 adverse event was reported in one trial. Conclusions: SBRT is highly cost effective, safe, and with an almost inexistent toxicity risk that makes it the perfect candidate for the optimal management of PCa oligometastatic patients. However, more solid data and a higher level of evidence are needed to affirm its role in the management of these patie

Background: Ultrasound-guided magnetic resonance imaging (MRI)-fusion biopsy and in-bore MRI-guided biopsy (MRGB) have improved the diagnostic pathway in patients with suspected prostate cancer compared to the traditional random sampling of the prostate gland under transrectal ultrasound guidance (TRUS-Bx). The aim of our study was to assess the psychological experiences of patients undergoing MRGB and TRUS-Bx. Method: Participants completed an ad hoc set of 11 items to be rated from 0 (not at all) to 10 (very much) on visual analogue scales and one open question on the most worrisome aspect of the procedure. The set of items evaluated satisfaction with the information received and the possibility to ask questions to the staff; the tolerability of the irritation, duration and discomfort associated with the exam; their level of worry or calm before the exam; the perceived need to undergo the exam; their satisfaction with the exam and willingness to repeat it in the future; and acceptability of the exam. Results: Between May 2018 and June 2019, 47 participants were enrolled on the day of their MRGB; 24 had previously undergone TRUS-Bx. The MRGB was rated with high positive scores on all 11 items. The lowest ratings regarded the duration of the exam (mean = 6.6) and feeling calm (mean = 6.6). Participants were significantly more satisfied with MRGB than TRUS-Bx, rating it as less painful and more comfortable, necessary and tolerable. Conclusion: These preliminary results indicate that the MRGB is likely to be more tolerable and acceptable to patients than TRUS-Bx.