How radical prostatectomy procedures have changed over the last 10 years in Italy: a comparative analysis based on more than 1500 patients participating in the MIRROR-SIU/LUNA and the Pros-IT CNR study.

PURPOSE: Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. METHODS: The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). RESULTS: The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%, p < 0.001) and NS prostatectomy (58.4% vs. 52.9%, p = 0.04), but received LND less frequently (47.7% vs. 76.7%, p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS ≥ (4 + 3) and positive cancer cores ≥ 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. CONCLUSIONS: PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

Impact of Surgical Approach on Patient-Reported Outcomes after Radical Prostatectomy: A Propensity Score-Weighted Analysis from a Multicenter, Prospective, Observational Study (The Pros-IT CNR Study).

BACKGROUND: To report health-related quality of life outcomes as assessed by validated patient-reported outcome measures (PROMs) after radical prostatectomy (RP). -Methods: This study analyzed patients treated with RP within The PROState cancer monitoring in Italy, from the National Research Council (Pros-IT CNR). Italian versions of Short-Form Heath Survey and university of California los Angeles-prostate cancer index questionnaires were administered. PROMs were physical composite scores, mental composite scores and urinary, bowel, sexual functions and bothers (UF/B, BF/B, SF/B). Baseline unbalances were controlled with propensity scores and stabilized inverse weights; differences in PROMs between different RP approaches were estimated by mixed models. RESULTS: Of 541 patients treated with RP, 115 (21%) received open RP (ORP), 90 (17%) laparoscopic RP (LRP) and 336 (61%) robot-assisted RP (RARP). At head-to-head -comparisons, RARP showed higher 12-month UF vs. LRP (interaction treatment * time p = 0.03) and 6-month SF vs. ORP (p < 0.001). At 12-month from surgery, 67, 73 and 79% of patients used no pad for urinary loss in ORP, LRP and RARP respectively (no differences for each comparison). Conversely, 16, 27 and 40% of patients declared erections firm enough for sexual intercourse in ORP, LRP and RARP respectively (only significant difference for ORP vs. RARP, p = 0.0004). CONCLUSIONS: Different RP approaches lead to significant variations in urinary and sexual PROMs, with a general trend in favour of RARP. However, their clinical significance seems limited.

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: the Pros-IT CNR study.

BACKGROUND: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. METHODS: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). RESULTS: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. CONCLUSIONS: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.

Pros-IT CNR: an Italian prostate cancer monitoring project.

AIMS: The Pros-IT CNR project aims to monitor a sample of Italian males ≥18 years of age who have been diagnosed in the participating centers with incident prostate cancer, by analyzing their clinical features, treatment protocols and outcome results in relation to quality of life. METHODS: Pros-IT CNR is an observational, prospective, multicenter study. The National Research Council (CNR), Neuroscience Institute, Aging Branch (Padua) is the promoting center. Ninety-seven Italian centers located throughout Italy were involved. The field study began in September 1, 2014. Subjects eligible were diagnosed with biopsy-verified prostate cancer, naïve. A sample size of 1500 patients was contemplated. A baseline assessment including anamnestic data, clinical history, risk factors, the initial diagnosis, cancer staging information and quality of life (Italian UCLA Prostate Cancer Index; SF-12 Scale) was completed. Six months after the initial diagnosis, a second assessment evaluating the patient's health status, the treatment carried out, and the quality of life will be made. A third assessment, evaluating the treatment follow-up and the quality of life, will be made 12 months after the initial diagnosis. The 4th, 5th, 6th and 7th assessments, similar to the third, will be completed 24, 36, 48 and 60 months after the initial diagnosis, respectively, and will include also a Food Frequency Questionnaire and the Physical Activity Scale for the Elderly. DISCUSSION: The study will provide information on patients' quality of life and its variations over time in relation to the treatments received for the prostate cancer.

The current management of mycosis fungoides and Sézary syndrome and the role of radiotherapy: Principles and indications.

AIM: To evaluate the current treatment of mycosis fungoides (MF) and Sézary syndrome (SS) focusing on the role of radiotherapy (RT), its principles and indications, and the perspectives of the novel irradiation technologies. BACKGROUND: MF and SS are rare lymphoproliferative diseases whose incidence is increasing. For a long time RT has been used as a single modality or in integrated treatment programs for these diseases. MATERIALS AND METHODS: The latest systematic reviews, primary studies and new diagnostic and treatment guidelines on MF and SS were analyzed. Clinical outcomes together with the technical aspects and the role of RT were also evaluated. RESULTS: New data are available on pathogenesis, diagnostic criteria, classification and staging procedures for MF and SS and several local and systemic therapies are proposed. Localized RT can cure "minimal stage" MF while total skin electron beam irradiation (TSEI) may cure initial-stage disease and may offer important symptom relief (itch, erythroderma) in a more advanced setting. Despite its efficacy, RT is not largely used, mainly because of some technical difficulties but new RT technologies may be proposed to treat large skin surfaces. CONCLUSIONS: New treatment programs offer good results, with median survival of more than 12 years in early-stage MF, but the median survival of 2.5 years or less in advanced stages is still a challenge. RT remains an option for all stages with a good cost/effectiveness ratio in a curative or palliative setting. New RT technologies can overcome some technical problems of treating large skin surfaces.

Cosmetic Results and Side Effects of Accelerated Partial-Breast Irradiation Versus Whole-Breast Irradiation for Low-Risk Invasive Carcinoma of the Breast: The Randomized Phase III IRMA Trial.

PURPOSE: The results in terms of side effects vary among the published accelerated partial-breast irradiation (APBI) studies. Here, we report the 5-year results for cosmetic outcomes and toxicity of the IRMA trial. METHODS: We ran this randomized phase III trial in 35 centers. Women with stage I-IIA breast cancer treated with breast-conserving surgery, age ≥ 49 years, were randomly assigned 1:1 to receive either whole-breast irradiation (WBI) or external beam radiation therapy APBI (38.5 Gy/10 fraction twice daily). Patients and investigators were not masked to treatment allocation. The primary end point was ipsilateral breast tumor recurrence. We hereby present the analysis of the secondary outcomes, cosmesis, and normal tissue toxicity. All side effects were graded with the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Radiation Morbidity Scoring Schema. Analysis was performed with both intention-to-treat and as-treated approaches. RESULTS: Between March 2007 and March 2019, 3,309 patients were randomly assigned to 1,657 WBI and 1,652 APBI; 3,225 patients comprised the intention-to-treat population (1,623 WBI and 1,602 APBI). At a median follow-up of 5.6 (interquartile range, 4.0-8.4) years, adverse cosmesis in the APBI patients was higher than that in the WBI patients at 3 years (12.7% v 9.2%; P = .009) and at 5 years (14% v 9.8%; P = .012). Late soft tissue toxicity (grade ≥ 3: 2.8% APBI v 1% WBI, P < .0001) and late bone toxicity (grade ≥ 3: 1.1% APBI v 0% WBI, P < .0001) were significantly higher in the APBI arm. There were no significant differences in late skin and lung toxicities. CONCLUSION: External beam radiation therapy-APBI with a twice-daily IRMA schedule was associated with increased rates of late moderate soft tissue and bone toxicities, with a slight decrease in patient-reported cosmetic outcomes at 5 years when compared with WBI, although overall toxicity was in an acceptable range.

The "Dark Side" of Picocyanobacteria: Life as We Do Not Know It (Yet).

Picocyanobacteria of the genus Synechococcus (together with Cyanobium and Prochlorococcus) have captured the attention of microbial ecologists since their description in the 1970s. These pico-sized microorganisms are ubiquitous in aquatic environments and are known to be some of the most ancient and adaptable primary producers. Yet, it was only recently, and thanks to developments in molecular biology and in the understanding of gene sequences and genomes, that we could shed light on the depth of the connection between their evolution and the history of life on the planet. Here, we briefly review the current understanding of these small prokaryotic cells, from their physiological features to their role and dynamics in different aquatic environments, focussing particularly on the still poorly understood ability of picocyanobacteria to adapt to dark conditions. While the recent discovery of Synechococcus strains able to survive in the deep Black Sea highlights how adaptable picocyanobacteria can be, it also raises more questions-showing how much we still do not know about microbial life. Using available information from brackish Black Sea strains able to perform and survive in dark (anoxic) conditions, we illustrate how adaptation to narrow ecological niches interacts with gene evolution and metabolic capacity.

Patient-Factors Influencing the 2-Year Trajectory of Mental and Physical Health in Prostate Cancer Patients.

This study aimed to examine the physical and mental Quality of Life (QoL) trajectories in prostate cancer (PCa) patients participating in the Pros-IT CNR study. QoL was assessed using the Physical (PCS) and Mental Component Score (MCS) of Short-Form Health Survey upon diagnosis and two years later. Growth mixture models were applied on 1158 patients and 3 trajectories over time were identified for MCS: 75% of patients had constantly high scores, 13% had permanently low scores and 12% starting with low scores had a recovery; the predictors that differentiated the trajectories were age, comorbidities, a family history of PCa, and the bowel, urinary and sexual functional scores at diagnosis. In the physical domain, 2 trajectories were defined: 85% of patients had constantly high scores, while 15% started with low scores and had a further slight decrease. Two years after diagnosis, the psychological and physical status was moderately compromised in more than 10% of PCa patients. For mental health, the trajectory analysis suggested that following the compromised patients at diagnosis until treatment could allow identification of those more vulnerable, for which a level 2 intervention with support from a non-oncology team supervised by a clinical psychologist could be of help.

Health-related quality of life 24 months after prostate cancer diagnosis: an update from the Pros-IT CNR prospective observational study.

BACKGROUND: This study analyzes patient health-related quality of life (QoL) 24-month after prostate cancer (PCa) diagnosis within the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study. METHODS: Pros-IT CNR is an ongoing, longitudinal and observational study, considering a convenience sample of patients enrolled at PCa diagnosis and followed at 6, 12, 24, 36, 48 and 60 months from the diagnosis. Patients were grouped according to the treatment received: nerve sparing radical prostatectomy (NSRP), non-nerve sparing radical prostatectomy (NNSRP), radiotherapy (RT), RT plus androgen deprivation (RT plus ADT) and active surveillance (AS). QoL was measured through the Italian versions of SF-12 and UCLA-PCI questionnaires at diagnosis and at 6-12 and 24-month. The minimal clinically important difference (MCID) was defined as half a standard deviation of the baseline domain. RESULTS: Overall, 1537 patients were included in the study. The decline in urinary function exceeded the MCID at each timepoint only in the NSRP and NNSRP groups (at 24 months -14.7, P<0.001 and -19.7, P<0.001, respectively). The decline in bowel function exceeded the MCID only in the RT (-9.1, P=0.02) and RT plus ADT groups at 12 months (-10.3, P=0.001); after 24 months, most patients seem to recover their bowel complaints. The decline in sexual function exceeded the MCID at each timepoint in the NNSRP, NSRP and RT plus ADT groups (at 6 months -28.7, P<0.001, -37.8, P<0.001, -20.4, P<0.001, respectively). CONCLUSIONS: Although all the treatments were relatively well-tolerated over the 24 month period following PCa diagnosis, each had a different impact on QoL.

The waiting time for prostate cancer treatment in Italy: analysis from the PROS-IT CNR Study.

BACKGROUND: Prostate cancer (PCa) is the second most common neoplasm in male patients. To date, there's no certain indication about the maximum waiting time (WT) acceptable for treatment beginning and the impact on oncological and functional outcomes has not been well established. METHODS: Data from the National Research Council PCa monitoring multicenter project in Italy (Pros-IT CNR) were prospectively collected and analyzed. WT was defined as the time from the bioptical diagnosis of PCa to the first treatment received. Patients were divided in two groups, using a time frame of 90 days. Quality of life was measured through the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and of the Short-Form Health Survey (SF-12). The occurrence of upgrading, upstaging, presence of lymph node metastasis and positive surgical margins at the final histopathological diagnosis, and PSA at 12 months follow-up were evaluated. RESULTS: The overall median WT was 93 days. The logistic multivariable model confirmed that age, being resident in Southern regions of Italy and T staging at diagnosis were significantly associated with a WT>90 days. At 6 months from diagnosis the mean SF-12 score for the emotional-psychological component was significantly lower in WT≥90 days group (P=0.0428). Among patients treated with surgical approach, no significant differences in oncological outcomes were found in the two groups. CONCLUSIONS: In our study age, clinical T stage and provenance from Southern regions of Italy are associated with a WT>90 days. WT might have no impact on functional and oncological outcome.

AIRO Breast Cancer Group Best Clinical Practice 2022 Update.

INTRODUCTION: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. METHOD: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. RESULTS: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. CONCLUSIONS: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation.

Adequate recovery of hematopoietic stem cell (HSC) niches after cytotoxic conditioning regimens is essential to successful bone marrow transplantation. Yet, very little is known about the mechanisms that drive the restoration of these niches after bone marrow injury. Here we describe a profound disruption of the marrow microenvironment after lethal total body irradiation of mice that leads to the generation of osteoblasts restoring the HSC niche, followed by a transient, reversible expansion of this niche. Within 48 hours after irradiation, surviving host megakaryocytes were observed close to the endosteal surface of trabecular bone rather than in their normal parasinusoidal site concomitant with an increased stromal-derived factor-1 level. A subsequent increase in 2 megakaryocyte-derived growth factors, platelet-derived growth factor-beta and basic fibroblast growth factor, induces a 2-fold expansion of the population of N-cadherin-/osteopontin-positive osteoblasts, relative to the homeostatic osteoblast population, and hence, increases the number of potential niches for HSC engraftment. After donor cell engraftment, this expanded microenvironment reverts to its homeostatic state. Our results demonstrate the rapid recovery of osteoblastic stem cell niches after marrow radioablation, provide critical insights into the associated mechanisms, and suggest novel means to manipulate the bone marrow microenvironment to promote HSC engraftment.

Plant scientists' research attention is skewed towards colourful, conspicuous and broadly distributed flowers.

Scientists' research interests are often skewed toward charismatic organisms, but quantifying research biases is challenging. By combining bibliometric data with trait-based approaches and using a well-studied alpine flora as a case study, we demonstrate that morphological and colour traits, as well as range size, have significantly more impact on species choice for wild flowering plants than traits related to ecology and rarity. These biases should be taken into account to inform more objective plant conservation efforts.

Impact of Gastrointestinal Side Effects on Patients' Reported Quality of Life Trajectories after Radiotherapy for Prostate Cancer: Data from the Prospective, Observational Pros-IT CNR Study.

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients' reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04-7.08; OR = 2.17, 95% CI 1.22-3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06-2.67; OR = 2.57, 95% CI 1.70-3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects.

Overview of potential determinants of radical prostatectomy versus radiation therapy in management of clinically localized prostate cancer: results from an Italian, prospective, observational study (the Pros-IT CNR study).

BACKGROUND: We assessed patients and tumor characteristics, as well as health-related quality of life (HRQoL) items, associated with curative intent treatment decision-making in clinically localized prostate cancer (PCa) patients. METHODS: Clinically localized PCa treated with either radical prostatectomy (RP) or radiation therapy (RT) within 12 months from diagnosis were abstracted from The PROState cancer monitoring in ITaly, from the National Research Council (Pros-IT CNR) database. Multivariable logistic regression (MLR) models predicting RT vs. RP were fitted, after adjustment for HRQoL items, patients and tumor characteristics. RESULTS: Of 1041 patients, 631 (60.2%) were treated with RP and 410 (39.8%) with RT. Relative to RT, RP patients were younger age (mean age 64.5±6.6 vs. 71.4±4.9, P<0.001) and had higher rates of D'Amico low-intermediate risk groups (31.8 vs. 21.9% low, 46.3% vs. 43.5% intermediate and 21.9% vs. 34.6% high risk, P<0.001). Overall, 93.2% of RP patients were enrolled by urologists and 82.7% of RT patients by radiation oncologists. RP patients had generally higher means values of HRQoL items. In MLR models, higher RT rates were independently associated with more advanced age (odds ratio [OR] 6.14, P<0.001) and BMI≥30 kg/m2 (OR 1.78, P<0.001). Conversely, lower rates of RT were independently associated with married (OR 0.55, P=0.01) and worker status (OR 0.52, P=0.004), enrollment in academic centers (OR 0.59, P=0.005) and higher physical composite score (OR 0.88, P=0.03) and baseline sexual function items (OR 0.92, P<0.001). CONCLUSIONS: Most patients with clinically localized prostate cancer undergoing definitive treatment at Italian institutions receive RP instead of RT. Moreover, those who are younger, married, working, as well as those with better physical and sexual function are more likely to undergo surgery.

PROLAPSE: survey about local prostate cancer relapse salvage treatment with external beam re-irradiation: results of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: We herein present the results of the first Italian Association of Radiotherapy and Clinical Oncology (AIRO) survey regarding salvage external beam re-irradiation of local prostate cancer relapse named PROLAPSE. METHODS: A questionnaire with 12 items was administered to the 775 Italian radiation oncologist members of the AIRO. RESULTS: One hundred of the members completed the survey. The survey highlighted that 59% of the participants are currently performing prostate re-EBRT, while nearly two-thirds (65%) affirmed that they are taking into consideration the procedure in case of intraprostatic relapse. Regarding the clinical target volume (CTV), only a minority (16%) declared to always prefer the partial prostate re-irradiation, while a consistent portion (nearly two-thirds) relied on clinical considerations of the choice towards partial or whole gland irradiation. The main techniques used for re-irradiation resulted to be intensity-modulated RT (IMRT)/volumetric modulated arc therapy (VMAT) and SBRT, having received approximately 40% of responses each. Regarding the criteria for patients' selection, more than 75% of responders agreed on the use of positron emission tomography (PET)/computed tomography (CT)-choline to exclude distant metastases and of multiparametric magnetic resonance imaging (mp-MRI) to detect intraprostatic recurrence. A sufficient timeframe (> 3 years) between primary RT and reirradiation was indicated by more than half of participants as an important driver in decision-making, while histological confirmation of the relapse was considered not essential by more than two-thirds. For the use of concomitant androgen deprivation therapy (ADT), most AIRO members (79%) agreed that the prescription should be based on a case-by-case analysis. Extreme hypofractionation (> 5 Gy/fraction) was preferred by the majority (52%) of the AIRO members. In most centers (more than 74%), the planning dose-volume constraints were generally extrapolated from the published data. In half of the cases, the interviewed responders affirmed that no major gastrointestinal (GI) and genitourinary (GU) toxicities were registered in the follow-up of their re-EBRT patients. Bladder complications represented the most commonly observed form of toxicity, with an incidence of 67%. CONCLUSION: This first AIRO survey about salvage prostate re-EBRT provides an interesting snapshot and suggests increasing interest in re-EBRT patients in Italy. Consensus about some aspects of patients' selection, the necessity of biopsy, fractionation, and highly selective techniques seems feasible, but other key points such as irradiated volume, dosimetry parameters, and hormonal treatment association need to be clarified.

Genomic Comparison and Spatial Distribution of Different Synechococcus Phylotypes in the Black Sea.

Picocyanobacteria of the genus Synechococcus are major contributors to global primary production and nutrient cycles due to their oxygenic photoautotrophy, their abundance, and the extensive distribution made possible by their wide-ranging biochemical capabilities. The recent recovery and isolation of strains from the deep euxinic waters of the Black Sea encouraged us to expand our analysis of their adaptability also beyond the photic zone of aquatic environments. To this end, we quantified the total abundance and distribution of Synechococcus along the whole vertical profile of the Black Sea by flow cytometry, and analyzed the data obtained in light of key environmental factors. Furthermore, we designed phylotype-specific primers using the genomes of two new epipelagic coastal strains - first described here - and of two previously described mesopelagic strains, analyzed their presence/abundance by qPCR, and tested this parameter also in metagenomes from two stations at different depths. Together, whole genome sequencing, metagenomics and qPCR techniques provide us with a higher resolution of Synechococcus dynamics in the Black Sea. Both phylotypes analyzed are abundant and successful in epipelagic coastal waters; but while the newly described epipelagic strains are specifically adapted to this environment, the strains previously isolated in mesopelagic waters are able, in low numbers, to withstand the aphotic and oxygen depleted conditions of deep layers. This heterogeneity allows different Synechococcus phylotypes to occupy different niches and underscores the importance of a more detailed characterization of the abundance, distribution, and dynamics of individual populations of these picocyanobacteria.

The mesopelagic anoxic Black Sea as an unexpected habitat for Synechococcus challenges our understanding of global "deep red fluorescence".

The Black Sea is the largest meromictic sea with a reservoir of anoxic water extending from 100 to 1000 m depth. These deeper layers are characterised by a poorly understood fluorescence signal called "deep red fluorescence", a chlorophyll a- (Chl a) like signal found in deep dark oceanic waters. In two cruises, we repeatedly found up to 103 cells ml-1 of picocyanobacteria at 750 m depth in these waters and isolated two phycoerythrin-rich Synechococcus sp. strains (BS55D and BS56D). Tests on BS56D revealed its high adaptability, involving the accumulation of Chl a in anoxic/dark conditions and its capacity to photosynthesise when re-exposed to light. Whole-genome sequencing of the two strains showed the presence of genes that confirms the putative ability of our strains to survive in harsh mesopelagic environments. This discovery provides new evidence to support early speculations associating the "deep red fluorescence" signal to viable picocyanobacteria populations in the deep oxygen-depleted oceans, suggesting a reconsideration of the ecological role of a viable stock of Synechococcus in dark deep waters.

Treatment paths for localised prostate cancer in Italy: The results of a multidisciplinary, observational, prospective study (Pros-IT CNR).

BACKGROUND: There are several treatments available to newly diagnosed prostate cancer (PCA) patients. Although surgery and radiotherapy (RT) with or without androgen deprivation therapy (ADT) are widely adopted treatment options for localized PCA together with active surveillance (AS), there is no consensus nor randomised trials on treatment selection, prospective quality of life (QOL), along with toxicity outcomes and according to treatment modality in the Italian population. The current study aimed to describe clinical-therapeutic features and QOL at PCA diagnosis, according to different treatment patterns in a large prospective, Italian population, enrolled in the Pros-IT CNR study. METHODS: The Pros-IT CNR is an on-going national, multicenter, observational, prospective study on patients affected by PCA who have been referred by 97 Italian Urology, Radiation Oncology and Medical Oncology facilities participating in the project. The possible relationships between the treatment patterns reported in the 6 month follow-up case report form and patients' features at diagnosis were evaluated using exploratory multiple correspondence analysis (MCA) and other data analysis method. RESULTS: At diagnosis, surgery and AS patients were significantly younger, had fewer comorbidities, lower PSA levels and Gleason Score (GS) values; they were also diagnosed at an earlier stage of disease with respect to the RT or ADT patients who showed significantly worse QoL scores at the time of diagnosis. CONCLUSIONS: An analysis of the data collected at baseline and 6 months later uncovered substantial differences in ages, comorbidities, clinical and QOL features in the various treatment groups. These findings do not fully reflect the current PCA treatment guidelines and suggest the need for a multidisciplinary consensus guideline to ameliorate both the counselling and treatments of PCA patients.

Recommendations for surveillance and follow-up of men with testicular germ cell tumors: a multidisciplinary consensus conference by the Italian Germ cell cancer Group and the Associazione Italiana di Oncologia Medica.

BACKGROUND: No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT). METHODS: In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions. RESULTS: Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse. CONCLUSIONS: The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.