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Background Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen receptor translocation and signalling. The aim of this study is to assess the efficacy of their concurrent administration in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). Methods In this open-label, randomised, phase II trial, previously untreated mCRPC patients were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m2, oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the same treatment without enzalutamide (arm D). The primary end-point was the percentage of patients without investigator-assessed disease progression 6 months after the first docetaxel administration. Results The 246 eligible patients were randomly assigned to receive docetaxel, prednisone and enzalutamide (n = 120) or docetaxel and prednisone (n = 126). The 6-month progression rate was 12.5% (95% confidence interval [CI] 8.1–20.6) in arm DE and 27.8% (95% CI 22.8–39.4) in arm D (chi-squared test 10.01; P = 0.002). The most frequent grade III–IV adverse events were fatigue (12.5% in arm DE versus 5.6% in arm D), febrile neutropenia (9.3% versus 4.0%) and neutropenia (7.6% versus 5.6%). Conclusions The combination of enzalutamide and docetaxel appears to be more clinically beneficial than docetaxel alone in previously untreated mCRPC patients, although serious adverse events were more frequent. Our findings suggest that first-line treatment with this combination could lead to an additional clinical benefit when prompt and prolonged disease control is simultaneously required. Clearly, these results should be considered cautiously because of the study’s phase II design and the absence of an overall survival benefit. Trial registration numbers EudraCT 2014-000175-43 – NCT02453009.

Gastrectomy for gastric cancer is still performed in Western countries with high morbidity and mortality. Post-operative complications are frequent, and effective diagnosis and treatment of complications is crucial to lower the mortality rates. In 2015, a project was launched by the EGCA with the aim of building an agreement on list and definitions of post-operative complications specific for gastrectomy. In 2018, the platform www.gastrodata.org was launched for collecting cases by utilizing this new complication list. In the present paper, the Italian Research Group for Gastric Cancer endorsed a collection of complicated cases in the period 2015–2019, with the aim of investigating the clinical pictures, diagnostic modalities, and treatment approaches, as well as outcome measures of patients experiencing almost one post-operative complication. Fifteen centers across Italy provided 386 cases with a total of 538 complications (mean 1.4 complication/patient). The most frequent complications were non-surgical infections (gastrointestinal, pulmonary, and urinary) and anastomotic leaks, accounting for 29.2% and 17.3% of complicated patients, with a median Clavien–Dindo score of II and IIIB, respectively. Overall mortality of this series was 12.4%, while mortality of patients with anastomotic leak was 25.4%. The clinical presentation with systemic septic signs, the timing of diagnosis, and the hospital volume were the most relevant factors influencing outcome.

Background. More than 50% of operable GEA relapse after curative-intent resection. We aimed at externally validating a nomogram to enable a more accurate estimate of individualized risk in resected GEA. Methods. Medical records of a training cohort (TC) and a validation cohort (VC) of patients undergoing radical surgery for c/uT2-T4 and/or node-positive GEA were retrieved, and potentially interesting variables were collected. Cox proportional hazards in univariate and multivariate regressions were used to assess the effects of the prognostic factors on OS. A graphical nomogram was constructed using R software’s package Regression Modeling Strategies (ver. 5.0-1). The performance of the prognostic model was evaluated and validated. Results. The TC and VC consisted of 185 and 151 patients. ECOG:PS > 0 (p < 0.001), angioinvasion (p < 0.001), log (Neutrophil/Lymphocyte ratio) (p < 0.001), and nodal status (p = 0.016) were independent prognostic values in the TC. They were used for the construction of a nomogram estimating 3- and 5-year OS. The discriminatory ability of the model was evaluated with the c-Harrell index. A 3-tier scoring system was developed through a linear predictor grouped by 25 and 75 percentiles, strengthening the model’s good discrimination (p < 0.001). A calibration plot demonstrated a concordance between the predicted and actual survival in the TC and VC. A decision curve analysis was plotted that depicted the nomogram’s clinical utility. Conclusions. We externally validated a prognostic nomogram to predict OS in a joint independent cohort of resectable GEA; the NOMOGAST could represent a valuable tool in assisting decision-making. This tool incorporates readily available and inexpensive patient and disease characteristics as well as immune-inflammatory determinants. It is accurate, generalizable, and clinically effectivex.

An improved weather-forecast-based link-budget design technique for space-to-Earth links is described. The aim is the stochastic optimization of both transmission symbol rate and received signal-to-noise ratio. The proposed radiometeorological operations prediction (RadioMetOP) model takes into account the forecast uncertainty by a space–time ensemble method exploiting the temporal evolution of the predicted radiometeorological variables over the weather-forecast spatial grid. The unique possibility of testing and validating the RadioMetOP model is presented, thanks to the $Ka$ -band downlink measurements available from the support of the European Space Agency’s antenna tracking network to deep-space Hayabusa-2 (HB2) mission, operated by the Japan Aerospace Exploration Agency. First, the RadioMetOP model accuracy is tested by comparing the signal-to-noise ratio, measured during the transmission periods, with the simulated one, properly scaled to the symbol rate operated by HB2, finding correlation values of 0.9 that confirm the effectiveness of the proposed approach. Second, the $a$ posteriori analysis of the optimization process is accomplished, showing that depending on the considered criteria for the link-budget optimization, the use of the RadioMetOP model would have allowed a transmitted data volume more than doubled and an average signal-to-noise ratio gain between 2.1 and 3.8 dB.

167 Background: Although CHAARTED trial suggested a survival advantage in de novo (DN) high volume (HV) mCSPC pts, the use of DOC is still debated according to the timing of either metastatic onset [relapsed (REL) vs DN] or disease burden [low volume (LV) vs HV]. In this view, it could be of interest to describe the real-world use of DOC. From 2014, ECHOS multicenter study is collecting real world data from mCSPC pts in Italy, where DOC was the only reimbursed agent until recently. Here, we present study results after first data lock at the end of 2021. Methods: We reviewed the clinical records of the mCSPC pts treated with DOC in 34 Italian Institutions. For each pt we recorded pre and post-DOC clinical history, baseline characteristics, treatment details and clinical outcomes. Results: We identified 568 pts [median age 66.5 yrs (range 43-85)]. Most of them were classified as having a DN/HV disease (78%): the remaining had a REL/LV (2.5%), a REL/HV (8.1%), and a DN/LV disease (11.5%). After a median follow-up of 22 mos, 389 pts experienced disease progression and 227 died. The survival outcomes according to the metastases timing and disease volume is reported in the table. Conclusions: Our real-world experience shows that DOC is proposed not only in DN/HV pts, but also in the other pts regardless of metastases timing and disease volume. The prognosis of DN/HV pts treated with DOC appears to be worse than in CHAARTED trial. These findings need to be confirmed by further analyses made on larger number of pts enrolled in the ECHOS trial. [Table: see text]

712 Background: Nivolumab, an immune checkpoint inhibitor of PD-1, demonstrated a significant OS benefit in patients with metastatic renal cell carcinoma (mRCC), in progression after a previous line of therapy with anti-VEGFR agents. However, the features of effective immune response and predictive biomarkers of clinical benefit to PD-1 blockade have not yet been recognized. Methods: I-RENE is a prospective translational multicenter Italian study of a real-life mRCC patients treated with nivolumab or cabozantinib after failure of therapy with anti-VEGFR agents. 82 patients were enrolled from December 2018 to August 2022 (nivo 60, cabo 22), with blood samples obtained at baseline and at different time points in both treatment groups. An extended concept of "immune liquid biopsy" is being applied to the study, consisting in the phenotypic and transcriptional profile of lymphoid and myeloid subsets, immune-related miRNA quantification, cyto/chemo-kinome and RNAseq of extracellular vesicle. Results: Multiparametric flow cytometry, performed to monitor the blood frequency and different myeloid and lymphoid cells, show that monocyte subsets (classical, intermediate and non-classical CD14+ cells), monocytic myeloid derived suppressor cells (MDSC, such as CD14+HLA-DRneg and CD14+PD-L1+) and polymorphonucleate (PMN)-MDSC, remain either stable or increase during treatment; concomitantly, CD8+PD-1+ T cells (detected by anti-nivolumab IgG4) increment frequency, acquire the effector CD45RA-CCR7+ phenotype and express the proliferating marker Ki67. Patients receiving cabozantinib display instead a remarkable decrease of all myeloid cell subsets, paired by the boost of cytotoxic CD3-CD16+CD56dim NK cells and more marginally of CD8+PD1+ cells, Preliminary correlations indicate that clinical benefit of nivolumab seems to cluster with the lack of CD14+ cells and M-MDSC increase and blood frequency of total, and the boost in CD8+CD45RA-CCR7+Ki67+ effector T cells. In contrast, the cabozantinib-induced immune modulation occurring in patients treated with does not associate with clinical response Conclusions: This first set of data indicate blood as promising source of dynamic biomarkers for the development of algorithms predicting response to PD-1 blockade. Furthermore, the results so far collected suggest that the potent immunomodulation induced by cabozantinib on the immunosuppressive myeloid compartment may not lead to any tumor control in the absence of specific immune stimulation by checkpoint inhibitors. This study was supported by the Italian Ministry of health (RF-2016_02363001). Clinical trials.gov: NCT04891055 Clinical trial information: NCT04891055 .

Background To reduce the overall exposure to dexamethasone (DEX) in patients receiving cisplatin‐based chemotherapy, we evaluated the noninferiority of DEX on day 1, with or without low‐dose DEX on days 2 and 3, combined with an oral fixed‐dose combination of netupitant and palonosetron (NEPA), compared with the guideline‐consistent use of 4‐day DEX. Patients and Methods In this open‐label, multicenter study, chemotherapy‐naïve patients undergoing high‐dose cisplatin (≥70 mg/m2), were given NEPA and DEX (12 mg) on day 1 and randomized (1:1:1 ratio) to receive either (a) no further DEX (DEX1), (b) oral DEX (4 mg daily) on days 2–3 (DEX3), or (c) DEX (4 mg twice daily) on days 2–4 (DEX4). The primary efficacy endpoint was complete response (CR: no emesis and no rescue medication) during the 5‐day overall phase. The noninferiority margin was set at −15% difference (DEX1 or DEX3 minus DEX4). Secondary efficacy endpoints included complete protection (CP: CR and none or mild nausea). Results Two‐hundred twenty‐eight patients, 76 in each arm, were assessable. Noninferiority was met for both DEX‐sparing regimens and the reference arm, with overall phase CR rates of 76.3% in each of the DEX1 and DEX3 arms and 75.0% in the DEX4 arm (95% confidence interval, −12.3% to 15% for each comparison). During the overall phase, CP rates were similar between groups. Conclusion A simplified regimen of NEPA plus single‐dose DEX offers comparable chemotherapy‐induced nausea and vomiting prevention throughout 5 days post‐chemotherapy with the advantage of sparing patients additional doses of DEX in the high–emetic‐risk setting of cisplatin‐based chemotherapy. Implications for Practice Dexamethasone (DEX) has traditionally played an integral role in the management of chemotherapy‐induced emesis. Although generally considered safe, even short‐term DEX use is associated with various side effects, and some evidence suggests that concurrent steroids may reduce the efficacy of immunotherapies. This study demonstrates comparable antiemetic control during the 5 days post‐chemotherapy with a simplified regimen of netupitant/palonosetron plus single‐dose DEX versus the standard 4‐day DEX reference treatment in high‐dose cisplatin. This represents a clinically relevant achievement as it not only simplifies antiemetic prophylaxis but also offers an opportunity to appropriately use in patients where caution with corticosteroid use is advised., This study was designed to test whether two different dexamethasone‐sparing regimens, when administered with NEPA, might provide the opportunity to reduce the total corticosteroid dose while maintaining the same degree of chemotherapy‐induced nausea and vomiting control in patients undergoing cisplatin‐based chemotherapy.