The European Association of Urology guidelines include the lutetium-177 (
Lu) PSMA-617 prostate-specific membrane antigen (PSMA) ligand as a therapy option for metastatic castration-resistant ...prostate cancer (mCRPC). A major challenge in clinical practice is to pursue a personalized treatment approach based on robust predictive biomarkers.
To assess the performance of
Lu PSMA in real-world practice and to elaborate clinical biomarkers for evaluating treatment responses.
We conducted a retrospective observational study including 233 patients with mCRPC treated with
Lu PSMA in eight high-volume European centers.
Baseline characteristics and clinical parameters during and after
Lu PSMA treatment were documented. Correlations to treatment response were analyzed using χ
and log-rank tests, with differences between groups with and without disease progression calculated using a Mann-Whitney U test. Univariate and multivariate-adjusted hazard ratios (HRs) were measured using Cox proportional hazards models.
A prostate-specific antigen (PSA) decrease of ≥30% was observed in 41.7%, 63.5%, and 77.8% of patients after the first, second, and third treatment cycle, respectively. Restaging performed via PSMA positron emission tomography-computed tomography revealed that 33.7% of patients had an imaging-based response, including two patients with a complete response, while 13.4% had stable disease. The median time to progression was 5 mo and the median time until the start of a consecutive antineoplastic therapy was 8.5 mo. Of importance, a PSA decrease ≥30% after the first two cycles of
Lu PSMA (1 cycle: p = 0.0003; 2 cycles: p = 0.004), absolute PSA after the first three cycles (1 cycle: p = 0.011; 2 cycles: p = 0.0005; 3 cycles: p = 0.002), and a PSA doubling time >6 mo (p = 0.009) were significantly correlated to treatment response. Furthermore, gamma-glutamyl transferase ≤31 U/L at the start of
Lu PSMA therapy was correlated with 1.5 times higher risk of progression for patients without but not with visceral metastases (p = 0.046).
Lu PSMA is an effective treatment option in mCRPC in the real-world setting. A PSA decrease ≥30% after the first two cycles is an early marker of response that can be easily implemented in clinical practice.
Lu PSMA is a radioactive agent approved for treatment of advanced prostate cancer. We reviewed its use outside of clinical trials for patients treated at eight European centers. We found that
Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy cycles is an early indicator of response to treatment and can be used in personalizing treatments for patients.
BACKGROUNDThe European Association of Urology guidelines include the lutetium-177 (177Lu) PSMA-617 prostate-specific membrane antigen (PSMA) ligand as a therapy option for metastatic ...castration-resistant prostate cancer (mCRPC). A major challenge in clinical practice is to pursue a personalized treatment approach based on robust predictive biomarkers.OBJECTIVETo assess the performance of 177Lu PSMA in real-world practice and to elaborate clinical biomarkers for evaluating treatment responses.DESIGN, SETTING, AND PARTICIPANTSWe conducted a retrospective observational study including 233 patients with mCRPC treated with 177Lu PSMA in eight high-volume European centers.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSISBaseline characteristics and clinical parameters during and after 177Lu PSMA treatment were documented. Correlations to treatment response were analyzed using χ2 and log-rank tests, with differences between groups with and without disease progression calculated using a Mann-Whitney U test. Univariate and multivariate-adjusted hazard ratios (HRs) were measured using Cox proportional hazards models.RESULTS AND LIMITATIONSA prostate-specific antigen (PSA) decrease of ≥30% was observed in 41.7%, 63.5%, and 77.8% of patients after the first, second, and third treatment cycle, respectively. Restaging performed via PSMA positron emission tomography-computed tomography revealed that 33.7% of patients had an imaging-based response, including two patients with a complete response, while 13.4% had stable disease. The median time to progression was 5 mo and the median time until the start of a consecutive antineoplastic therapy was 8.5 mo. Of importance, a PSA decrease ≥30% after the first two cycles of 177Lu PSMA (1 cycle: p = 0.0003; 2 cycles: p = 0.004), absolute PSA after the first three cycles (1 cycle: p = 0.011; 2 cycles: p = 0.0005; 3 cycles: p = 0.002), and a PSA doubling time >6 mo (p = 0.009) were significantly correlated to treatment response. Furthermore, gamma-glutamyl transferase ≤31 U/L at the start of 177Lu PSMA therapy was correlated with 1.5 times higher risk of progression for patients without but not with visceral metastases (p = 0.046).CONCLUSIONS177Lu PSMA is an effective treatment option in mCRPC in the real-world setting. A PSA decrease ≥30% after the first two cycles is an early marker of response that can be easily implemented in clinical practice.PATIENT SUMMARY177Lu PSMA is a radioactive agent approved for treatment of advanced prostate cancer. We reviewed its use outside of clinical trials for patients treated at eight European centers. We found that 177Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy cycles is an early indicator of response to treatment and can be used in personalizing treatments for patients.
This study analysed the meat fatty acid (FA) composition of three zebu breeds, Gudali (GU), White Fulani (WF) and Red Mbororo (RM), raised on savannah pasture and monitored in the commercial context ...of the Yaoundé abattoir. Samples of m. longissimus thoracis from 60 bulls belonging to the GU, WF and RM breeds were collected and analysed for fat and FA composition. The fat content of the meat was low, but similar across breeds (1.34 ± 0.912 g/100 g muscle, mean ± SD). Meat from the GU breed had higher C18:3n-3 and C22:5n-3 proportions and lower C18:0 and total saturated FA proportions than WF meat. Red Mbororo meat had an intermediate FA composition compared with the other breeds. The elongase and ∆9 desaturase indices were comparable among breeds. In summary, the results indicate that there are minimal differences in beef FA composition of the three breeds from the Central African sub-region. Additionally, based on the polyunsaturated FA (PUFA) proportion, 13.9% of the total lipids and n-6/n-3 PUFA ratio, 1.95, consumption of beef from these breeds could be beneficial to human health. This is possibly owing to the pasture feeding and low fat content of the beef.
The reactions of a series of differently substituted nitrobenzofuroxans with isoprene and 2,3-dimethylbutadiene have been investigated. A variety of mono- and di-adducts resulting from normal ...electron demand Diels–Alder condensations involving the activated C
6C
7 and/or C
4C
5 double bonds of the carbocyclic ring as the dienophile contributors have been identified and structurally characterized. The regioselectivity of the reactions is found to be strongly dependent on the substitution pattern of this ring. In the 4-nitro-6-X-series, the diene molecule first adds to the C
6C
7 double bond if X is a strong electron-withdrawing substituent (X=NO
2, SO
2CF
3) but to the nitroactivated C
4C
5 double bond if X is a moderately activating substituent (X=CN, CF
3). Subsequent addition of a second molecule of diene occurs to give highly stereoselective diadducts in the 6-cyano, 6-trifluoromethyl and 6-nitro systems. Contrasting with this behavior, only monoadducts corresponding to the addition of diene to the nitroactivated C
6C
7 double bond were obtained in the 4-X-6-nitro-series (X=CN, CF
3). 4,6-Dinitrotetrazolo1,5-
apyridine reacts similarly to 4,6-dinitrobenzofuroxan, i.e. highly stereoselective diadducts are formed on the reaction with isoprene and 2,3-dimethylbutadiene. A most significant finding is that the treatment of some of the isolated mono- and di-adducts by a strong base like
t-BuOK results in a facile β-elimination of nitrous acid. Concomitant oxidative rearomatization of the resulting cyclohexadiene moieties then occurs spontaneously to afford otherwise difficultly available naphtho- or phenanthreno furoxanic or furazanic structures as well as azaphenanthrenotetrazoles.
Graphic
Alpine transhumant systems are based on utilization of lowland forages in Winter and pastures in Summer. Milk produced by two homogeneous groups of 25 Italian Simmental cows, reared respectively in ...lowland and in highland, was processed separately for 3 consecutive days in July. On cheeses, ripened for 3 months, chemical, rheological, sensory analyses were carried out and volatile compounds, related to cheese flavour, were studied. The results showed differences between the two types of cheese in terms of chemical composition, sensory traits and flavour components.
I sistemi transumanti alpini utilizzano foraggi di fondovalle d´inverno e pascoli d´estate. Il latte prodotto da 2 gruppi omogenei di 25 bovine Pezzate Rosse Italiane, allevate rispettivamente in fondovalle e in alpeggio, è stato caseificato separatamente per 3 giorni consecutivi nel mese di luglio. Sui formaggi, stagionati per 3 mesi, sono state condotte analisi chimiche, reologiche, sensoriali e dei composti aromatici. I risultati hanno evidenziato differenze tra i due tipi di formaggio in termini di composizione chimica, caratteristiche sensoriali e componenti aromatiche
Effect of milk feeding system on carcass and meat quality of Frisa Valtellinese kids [Lombardy] Piasentier, E. (Udine Univ. (Italy). Dipartimento di Scienze Animali); Volpelli, L.A. (Udine Univ. (Italy). Dipartimento di Scienze Animali); Sepulcri, A. (Udine Univ. (Italy). Dipartimento di Scienze Animali) ...
Italian journal of animal science,
01/2005, Letnik:
4, Številka:
2s
Journal Article
Recenzirano
Odprti dostop
Sixteen Frisa Valtellinese kids were fed on natural milk (N) suckled from their dams or on milk replacer (A) and slaughtered at approximately 17 kg live weight. The administration of milk replacer ...increased gross dressing percentage (45.6 vs 48.6% for N and A), as a consequence of lower gut content. The rearing system had a scarce effect on cut yield, while the carcass of A kids showed a higher fatness (fatness score: 3.5 vs 2.5 points). The most important quality traits of the meat (final pH, colour, cooking loss, shear force, proximate composition) were not modified by diet; however, the meat of naturally fed kids was richer in C18:3 and C20:5, with a more favourable ratio n-3/n-6 (0.77 vs 0.45).
Sedici capretti di razza Frisa Valtellinese sono stati allattati naturalmente (N) o con sostituto del latte (A) e macellati a circa 17 kg di peso. L´alimentazione artificiale ha prodotto un aumento della resa lorda di macellazione (45,6 vs 48,6% per N e A), a causa soprattutto del minor contenuto dell´apparato digerente. Il sistema di allattamento ha avuto una scarsa influenza sulla resa in tagli, mentre la carcassa dei capretti A ha mostrato un maggior rivestimento adiposo (stato d´ingrassamento: 3,5 vs 2,2 punti). I principali parametri di qualità della carne (pH finale, colore, perdite alla cottura, resistenza al taglio, analisi tipo) non sono stati modificati dalla dieta; tuttavia, la carne dei capretti allattati naturalmente è risultata più ricca di C18:3 e C20:5, con un più favorevole rapporto n-3/n-6 (0,77 vs 0,45)
The maximal explosive power during a two legs jump was measured on four competitive athletes mean age 24(SD 4.3) years; height 1.79 (SD 0.09) m; body mass 68.7 (SD 12.8) kg at different starting knee ...angles (70, 90, 110, 130 and 150 degrees). The experiments were performed on a newly developed instrument with which both force and speed could be measured using a force platform and a wire tachometer, respectively, and on a conventional force platform. At the smallest knee angle (70 degrees) the mean power output (W in watts per kilogram) developed during the jump was found not to differ significantly between the two methods (P > 0.1). At the larger knee angles W was 18.4% (90 degrees), 34.5% (110 degrees), 47.4% (130 degrees) and 19.4% (150 degrees) higher using the conventional force platform (P < 0.05 throughout). The difference of W between the two methods was attributed to the recovery of elastic energy due to the counter movement which immediately preceded the jump on the conventional platform, but not on the newly developed instrument. Indeed because of a mechanical arrangement which prevented the subject from moving towards the platforms, eccentric work (W-) could not be performed on the newly developed instrument; whereas W- on the conventional force platform was almost negligible at 70 degrees knee angle mean 1.7 (SD 2.3 J) reached a maximum of 13.1 (SD 7.9) J at 130 degrees and decreased again to a mean 4.7 (SD 3.6) J for the largest angle (150 degrees). Furthermore, on the conventional force platform, the force at the onset of the positive speed phase (Fi) was an increasing function of W- (r2 = 0.519, P < 0.001); and the difference of W between the conventional and new instruments was larger the larger the difference of Fi (r2 = 0.391, P < 0.01).
Differenze qualitative di formaggi prodotti a fondovalle e in alpeggio nell'ambito del sistema transumante alpino. I sistemi transumanti alpini utilizzano foraggi di fondovalle d'inverno e pascoli ...d'estate. Il latte prodotto da 2 gruppi omogenei di 25 bovine Pezzate Rosse Italiane, allevate rispettivamente in fondovalle e in alpeggio, è stato caseificato separatamente per 3 giorni consecutivi nel mese di luglio. Sui formaggi, stagionati per 3 mesi, sono state condotte analisi chimiche, reologiche, sensoriali e dei composti aromatici. I risultati hanno evidenziato differenze tra i due tipi di formaggio in termini di composizione chimica, caratteristiche sensoriali e componenti aromatiche.
PDF
