Использование барий-стронциевого карбонатита при изготовлении сварочных флюсов на основе техногенных отходов металлургического производства

В данной работе рассмотрена возможность использования барий-стронциевого карбонатита при изготовлении сварочных флюсов на основе шлака производства силикомарганца, а так же на основе ковшевых электросталеплавильных шлаков, образованных при производстве рельсовых марок стали. В серии опытов в лабораторных условиях изготавливали и исследовали различные составы сварочных флюсов, были определены химические составы наплавленного металла, проведен металлографический анализ.In this paper the possibility of using barium-strontium carbonatite in the manufacture of welding fluxes on the basis of slag from the production of silicomanganese, and based on ladle steelmaking slags formed in the production of rail steel grades. In a series of experiments in the laboratory have produced and investigated different compositions of welding fluxes, were determined the chemical compositions of the weld metal metallographic analysis

Efficacy and toxicity of [177Lu]Lu-PSMA-617 for metastatic castration-resistant prostate cancer in a real-world setting: Results from the U.S. Expanded Access Program and comparisons with phase 3 VISION data.

e17061 Background: ThePhase 3 VISION trial demonstrated that [177Lu]Lu-PSMA-617 prolonged overall survival (OS) in metastatic-castration resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor-signaling inhibitors (ARSi). The expanded access program (EAP) (NCT04825652) was opened to provide access to [177Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. The VISION trial required strict inclusion and exclusion criteria, which may not represent the patient population encountered in clinical practice. This study aimed to evaluate the efficacy and safety profile of [177Lu]Lu-PSMA-617 in a real-world setting within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP between May 2021 and March 2022 at four institutions in the United States with available toxicity and outcome data were included. Outcome measures included overall survival (OS), ≥50% PSA decline rates (PSA-RR), and incidences of toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Differences in baseline characteristics, toxicity, and PSA-RR between the EAP and VISION were evaluated using a t-test of proportions. Results: 117 patients with mCRPC were eligible and included. Patients enrolled in the EAP were similarly pretreated with taxane-based chemotherapy regimens (>1 taxane: 47% vs 40%; p=0.16) and more heavily pretreated with ARSi (>1 ARSi: 70% vs 46%; p<0.001). EAP patients had similar levels of ≥3 grade anemia (18% vs 13%; p=0.15), thrombocytopenia (13% vs 8%; p=0.13), and neutropenia (3% vs 3%; p=0.85) and higher levels of ≥3 grade lymphopenia (34% vs 8%; p<0.001). Patients treated within the EAP experienced numerically shorter OS (median OS: 13.7 vs 15.3 months) and similar PSA-RR (40% vs 46%; p=0.29). Median follow-up was numerically shorter in the EAP compared with VISION (14.7 mo vs 20.3 mo). Conclusions: mCRPC patients treated with [177Lu]Lu-PSMA-617 in a real-world setting were more heavily pretreated with ARSi, had a similar safety profile, and experienced numerically shorter OS and similar PSA-RR compared with VISION trial patients. A major limitation of this study is that we did not have access to individual patient data from the VISION trial, so we were not able to assess whether differences in OS between VISION and the EAP were statistically significant

ORCHID: A phase II study of olaparib in metastatic renal cell carcinoma patients harboring a BAP1 or other DNA repair gene mutations.

TPS400 Background: Metastatic renal cell carcinoma (RCC) comprises a wide set of heterogenous tumors, many of which are increasingly recognized with alterations that affect genomic instability. Several studies demonstrated that DNA repair pathways are frequently disrupted in RCC. Recent In vitro studies have shown that RCC cells are sensitive to PARP inhibitors, with subsequent increased DNA replication stress, DNA synthesis suppression and eventual increased cell cycle arrest. In addition, other studies demonstrated reduced repair of double stranded DNA (dsDNA) breaks following conditional knockout of BAP-1 suggesting that PARP inhibitors may result in synthetic lethality in the setting of BAP-1 inactivation. In light of this we have initiated a phase 2 clinical trial to examine the activity of the PAPR inhibitor olaparib in metastatic RCC with BAP-1 and select DNA repair gene alterations. Methods: This is an open-label, single-arm, investigator-initiated phase II trial of olaparib in patients with metastatic RCC (NCT03786796). Eligibility criteria include age ≥18 years; histologically confirmed, unresectable, locally advanced or mRCC; disease progression after at least one VEGF targeted therapy or immune-checkpoint inhibitor, evidence of deleterious somatic or germline DDR gene alteration ( BAP1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L). A total of 20 patients will be enrolled with the primary endpoint of disease control rate (defined as complete response [CR], partial response [PR], or stable disease [SD]) at six months of treatment) according to RECIST version 1.1. Patients will be treated with olaparib at an initial dose of 150mg by mouth twice daily. If olaparib is tolerated without any grade &gt; 3 adverse events after one month, the dose will be increased to the FDA-approved dose of 300mg by mouth twice daily. Patients will be followed monthly with clinic visits, safety labs, and toxicity assessments. Treatment will be continued until radiographic progression (RECIST version 1.1) or unmanageable toxicity requiring drug cessation. Secondary endpoints include progression-free survival, best overall response, and safety. The study is currently open to enrollment. Clinical trial information: NCT03786796. </jats:p

A Phase 3, randomized, double-blind, placebo-controlled study of tasquinimod (TASQ) in men with metastatic castration-resistant prostate cancer (mCRPC), secondary endpoints.

239 Background: TASQ is an oral agent with immunomodulatory, anti-angiogenic and anti-metastatic properties that targets the tumor microenvironment. It was recently reported from this study that in chemotherapy-naïve men with mCRPC, single-agent TASQ statistically significantly improved rPFS, by both central (HR (95% CI) 0.64 (0.54-0.75)) and local review, as compared to PBO but no OS benefit was demonstrated (HR (95% CI) 1.10 (0.94-1.28)). In this abstract the results of secondary efficacy endpoint analyses are presented. Methods: Men with asymptomatic to mildly symptomatic chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive TASQ or PBO once daily until progression or toxicity. Randomization was stratified by KPS ( ≥ 90% vs &lt; 90%), presence/absence of visceral disease, and geographic region. The secondary efficacy endpoints discussed here include a panel of radiological, PSA based and symptomatically assessed measures. Results: 1245 pts were randomized (TASQ, n = 832; PBO, n = 413) between 29 Mar 2011 and 7 Dec 2012 at 240 sites in 37 countries. Baseline characteristics were balanced between the 2 groups. In general, all radiology-based and PSA-based secondary endpoints showed statistically significant differences between TASQ and PBO in favor of TASQ. E.g. median time to radiological progression was 8.4 m for TASQ vs. 5.5 m for PBO, p &lt; 0.001, HR (95% CI) 0.628 (0.534-0.739) by central assessment. However, symptomatically assessed endpoints in general showed statistically significant differences in favor of PBO. E.g. median time to symptomatic progression was 9.5 m for TASQ vs. 11.9 m for PBO, p = 0.031, HR (95% CI) 1.171 (1.014-1.353). Grade ≥ 3 TEAEs were more common with TASQ than PBO (42.8 vs 33.6%). Conclusions: Outcome of the radiological and PSA-based endpoints favor TASQ in contrast to the symptomatically assessed endpoints, which favor placebo. Overall survival was not improved, which may be due to limited efficacy of TASQ in the studied population, toxicity, or the differential use of effective life-prolonging agents post-TASQ/placebo. Clinical trial information: NCT01234311. </jats:p

Risk factors for metastatic prostate cancer: A sentinel event case series.

235 Background: After 25 years of declines in late stage prostate cancer (PCa), evidence is mounting that an increasing fraction of men may present with metastatic disease, well after they might have been treated with local therapy. Identification of modifiable risk factors may allow for systems-level interventions to reduce delayed diagnoses. Methods: We performed an in-depth case series analysis of 15 patients who presented with metastatic disease at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center using root cause analysis, a tool commonly employed to understand the root cause of dangerous adverse events. Results: Key factors in late diagnosis include lack of insurance, lack of routine PSA testing, comorbidities, reluctance of patients to follow up actionable PSA as well as aggressive disease. Three patients had aggressive disease that would likely not have been discovered at an early stage regardless screening. However, analysis of the remaining 12 patients illuminated how health system factors led to missing important diagnostic information might have led to diagnosis of PCa at an earlier stage. Conclusions: These cases emphasize the need for systems-based approaches to early diagnosis of prostate cancer, which may prevent men from missing the opportunity to cure prostate cancer at an early stage. These results show how one might target PCa screening recommendations to more fully reflect key risk factors such as race and family history. </jats:p

Visceral metastases on abiraterone vs. placebo: A post-hoc analysis of mode of radiographic progression in COU-AA-302.

194 Background: Abiraterone prolongs survival in patients with prostate cancer due to its potent inhibition of androgen synthesis. We previously observed increased rates of visceral metastatic disease at the time of progression on abiraterone compared to baseline, a poor prognostic feature associated with non-AR dependent prostate cancer. We hypothesized that the rate of development of visceral disease was increased with abiraterone compared to other treatments without potent androgen signaling inhibition. In order to test this, we examined time to visceral disease among patients treated with abiraterone vs placebo on the COU-AA-302 trial. Methods: We performed a post-hoc analysis of radiographic progression data for the phase 3 study of abiraterone vs placebo, via a data sharing agreement through the Yale Open Data Access Project. Data were censored at end of study treatment. The distribution of cumulative incidence for visceral metastases was calculated by the Kaplan-Meier method and compared with log-rank testing. Multivariable cox regression analysis was performed to assess for independent association of study treatment (abiraterone vs placebo) with the development of visceral metastases. Results: Median follow-up was 12.5mo, and 84 of 1088 patients developed visceral metastases. Univariate log-rank testing showed no difference in time to visceral metastasis between groups (p = 0.97). 1- and 3-yr cumulative incidence of visceral metastases were estimated at 6.4% and 15.6% for abiraterone and 4.6% and 17.0% for placebo, respectively. Study treatment was not a significant predictor for the development of visceral metastasis (HR 0.76; 95% CI 0.47-1.21) after adjustment for baseline metastatic disease burden (soft tissue and bone) and LDH. Conclusions: Abiraterone was not associated with increased visceral metastases at progression compared to placebo. These data give more confidence to oncologists that abiraterone is not driving prostate cancer to an aggressive phenotype characterized by visceral metastases - a finding that is particularly important as abiraterone is increasingly used in early disease states. </jats:p

Changes in prostate-specific antigen doubling time (PSADT) prior to and after treatment with hormonal therapy (HT) in men with biochemically recurrent prostate cancer (BRPC): A preliminary analysis.

e15188 Background: PSADT is an important prognostic parameter in all clinical states of PCA. Intra -subject changes in PSADT prior to and after HT remains undefined. Methods: Men with rising serum PSA levels after local therapy were longitudinally followed from the hormone-sensitive (HS) to the castration-resistant (CR) state. PSADT was calculated according to standard formulas ( Pound et al., JAMA 1999) and previously identified prognostic subgroups (Antonarakis et al., BJU Int 2012; Freedland et al., JCO 2007) were used to evaluate the potential clinical significance of PSADT according to the following subgroups: [1] &lt; 3 months (mo); [2] 3-8.9 mo, [3] 9-14.9 mo, and [4] ≥ 15 mo). Results: 55 men with BRPC who eventually developed CR disease on HT were retrospectively analyzed. The median age of HS men was 60 y (range (r) 43-78); CR men 66 y (r 43-87). Of all men, 28 had prior surgery (S), 5 had radiation (R), 14 had S+R, 7 had neoadjuvant /adjuvant HT + local therapy, and 1 had no local therapy. PSADT in the CR state was shorter than PSADT in the HS state (signed –rank test; p=0 .012). HS men with PSADT &lt; 4 m had shorter overall survival than those with PSADT ≥ 4 mo ( 13.9 vs. 20.1 mo; HR ; 8.46). Changes in PSADT from the HS to the CR state are summarized in the Table below. The majority of men converted from a more favorable to a less favorable PSADT subgroup as they progressed from HS to CR states. Conclusions: PSADT tends to shorten from the HS to the CR states. The prediction of clinical outcome based on PSADT needs to account for the clinical state the patient is in, as PSADT may change within the same patient from state to state. [Table: see text] </jats:p

When using patient-reported outcomes in clinical practice, the measure matters: Results from an RCT.

6519 Background: Patient-reported outcomes (PRO) assess patients' perspectives on the impact of diseases and treatments. There is increasing interest in having patients complete PRO questionnaires and using the data clinically to identify and address patients' issues. There are many different PRO questionnaires, and this study investigated whether one PRO is more appropriate than others for clinical use. Methods: This controlled trial randomly assigned patients to complete 1 of 3 PRO questionnaires: six domains from the Patient Reported Outcomes Measurement Information System (PROMIS), the EORTC QLQ-C30, or the Supportive Care Needs Survey-Short Form (SCNS). Breast or prostate cancer patients, &gt;=21 years old, undergoing treatment, with oncologist visits at least monthly were eligible. Patients completed their assigned PRO questionnaire via computer either in the clinic or via the web prior to their clinic visits for the duration of active treatment. The results were provided to their clinicians for use during visits. After treatment ended, patients completed a 13-item feedback form to assess the impact of the questionnaire on their care (e.g., easy to complete, promoted communication, improved care quality). We hypothesized that there would be no difference in the proportion of patients who strongly agreed/agreed to all 13 items in the feedback form by questionnaire arm. Results: Of 294 eligible patients approached, 224(76%) enrolled (mean age 66, 78% white, 28% breast, 72% prostate). Of these, 181 patients (81%) responded to the feedback form, with 116 patients (52%) completing all 13 items. Of the 116 patients with complete data, subjects in the QLQ-C30 arm were most likely to strongly agree/agree to all items (82%), followed by PROMIS (62%), and SCNS (56%) [p=.05]. Among the 181 patients with at least partial data, the proportions strongly agreeing/agreeing to all items were 74% for QLQ-C30, 61% for PROMIS, and 52% for SCNS [p=.03]. Conclusions: In a randomized trial comparing the benefits of PROs applied in clinical practice, we found significant differences among the 3 PRO questionnaires. Future applications of PROs for patient care should select the most appropriate PRO measures for the purpose and setting. </jats:p