Role of radium-223 discontinuation due to adverse events in castration-resistant prostate cancer patients. A retrospective monocentric analysis.

BACKGROUND: Radium 223 (Ra-223) was approved for the treatment of metastatic castration resistant prostate cancer (mCRPC) patients with bone-only disease, following demonstration of significant improvement in overall survival (OS). To date, there are no validated prognostic factors useful in predicting outcome of mCRPC patients treated with Ra-223. Our retrospective study aims to evaluate the prognostic role of treatment discontinuation due to adverse events in mCRPC patients treated with Ra-223, and to identify which factors correlate with the toxicity onset. METHODS: We performed a retrospective analysis of all consecutive mCRPC patients treated with Ra-223 from September 2013 to December 2019 at our institute. Patients were divided in 2 groups according to the reason of Ra-223 therapy discontinuation: toxicity versus other causes. Outcome measures were progression-free survival (PFS) and OS. RESULTS: In the overall population (75 patients) median PFS and OS were 5.46 months and 11.15 months respectively. Patients who discontinued treatment due to toxicity had a lower median PFS (3.49 vs 5.89 months, HR: 1.88, 95% CI: 1.14-3.12, p = 0.014) and OS (8.59 vs 14.7 months HR: 3.33, 95% CI: 1.85-6.01, p < 0.001) than patients who discontinued therapy due to other causes. The risk of Ra-223 discontinuation due to toxicity correlates with the number of previous treatments (p = 0.002), previous chemotherapy treatment (p = 0.039), baseline LDH (p = 0.012), Hb (p = 0.021) and platelet-to-lymphocyte ratio (p = 0.024). CONCLUSIONS: Discontinuation due to toxicity is associated with worse outcomes in mCRPC patients treated with Ra-223. To reduce the risk of developing toxicities that may compromise treatment efficacy, Ra-223 should be used early in mCRPC patients.

Prognostic factors in metastatic castration resistant prostate cancer patients treated with radium-223: a retrospective study.

BACKGROUND: Our study aims to identify baseline prognostic factors in metastatic castration resistant prostate cancer (mCRPC) patients treated with radium-223. METHODS: Data about demographics, ECOG performance status, lymph node (LN) involvement, local treatment for prostate cancer, previous systemic treatments, cells blood count, PSA, ALP, albumin, LDH, bone protecting agents use (BPA), analgesic use and survival were collected. Univariable and multivariable analyses were performed. RESULTS: Seventy-five men received radium-223 between September 2013 and December 2019. Median age was 73 years. Thirty-four (45.3%) had ECOG PS 0, 41 (54.7%) PS 1-2. In univariable analysis, LN involvement (HR 1.68, 95% CI 1.01-2.80, P=0.047), absence of local treatment on primary tumor (HR 1.93, 95% CI 1.13-3.29, P=0.016), baseline strong opioidsuse (HR 1.82, 95% CI 1.08-3.06, P=0.024), high platelets to lymphocyte ratio (PLR) (HR 1.91, 95% CI 1.06-3.45, P=0.03), high baseline ALP (HR 1.81, 95% CI 1.10-2.99, P=0.019) and high baseline LDH (HR 3.86,95% CI 2.01-7.41, P<0.001) were significantly associated with worst OS. At multivariable analysis, LN involvement, strong opioids use, baseline ALP, LDH and PLR levels were significantly associated with outcome. CONCLUSIONS: In mCRPC patients treated with Radium-223, baseline ALP, LDH, strong opioid use, PLR, LN involvement and treatment on primary site are associated with different OS.

Strange case of biventricular heart failure.

Acute heart failure (HF) is commonly caused by a cardiomyopathy with one or more precipitating factor. Here, a case in which a cardiomyopathy is precipitated by pulmonary embolism (PE). A 77-year-old man is admitted for breathlessness and leg swelling. A mild reduction of left ventricular (LV) ejection fraction is found, with moderately increased LV wall thickness and pulmonary hypertension; clinical examination revealed signs of congestion with bilateral leg swelling, and mild signs of left HF with the absence of pulmonary congestion on chest X-ray. The ECG showed Mobitz I second-degree atrioventricular block. The clinical scenario led us to the diagnosis of infiltrative cardiomyopathy due to cardiac amyloidosis (CA) precipitated by PE. Pulmonary embolism is an overlooked precipitant of HF and can be the first manifestation of an underlying misdiagnosed cardiomyopathy, especially CA. 3,3-Diphosphono-1,2-propanodicarboxylic acid scan is a cornerstone in the diagnosis of Transthyretin amyloidosis (ATTR) cardiac amyloidosis.

223Ra Dichloride Bone-Targeted Therapy in a Case of Metastatic Salivary Duct Carcinoma.

Salivary duct carcinoma (SDC) is a rare malignancy, frequently overexpressing androgen receptor (AR). Therefore, similar to AR-positive prostate cancer (PCa), AR-positive SDC patients benefit from androgen deprivation therapy and, after progression on ADT, might take advantage of Ra dichloride, a radiopharmaceutical approved for the treatment of castration-resistant PCa with symptomatic bone disease. We report the case of a 75-year-old man with castration-resistant SDC and osteoblastic bone metastases who, after Ra treatment, achieved adequate control of bone pain and bone lesion reduction with minor side effects. Evaluation of this strategy in other patients with similar characteristics is warranted.

Semi-quantitative analysis of salivary gland scintigraphy in Sjögren's syndrome diagnosis: a first-line tool.

OBJECTIVE: The aim of this study was the assessment of semi-quantified salivary gland dynamic scintigraphy (SGdS) parameters independently and in an integrated way in order to predict primary Sjögren's syndrome (pSS). MATERIALS AND METHODS: Forty-six consecutive patients (41 females; age 61 ± 11 years) with sicca syndrome were studied by SGdS after injection of 200 MBq of pertechnetate. In sixteen patients, pSS was diagnosed, according to American-European Consensus Group criteria (AECGc). Semi-quantitative parameters (uptake (UP) and excretion fraction (EF)) were obtained for each gland. ROC curves were used to determine the best cut-off value. The area under the curve (AUC) was used to estimate the accuracy of each semi-quantitative analysis. To assess the correlation between scintigraphic results and disease severity, semi-quantitative parameters were plotted versus Sjögren's syndrome disease activity index (ESSDAI). A nomogram was built to perform an integrated evaluation of all the scintigraphic semi-quantitative data. RESULTS: Both UP and EF of salivary glands were significantly lower in pSS patients compared to those in non-pSS (p < 0.001). ROC curve showed significantly large AUC for both the parameters (p < 0.05). Parotid UP and submandibular EF, assessed by univariated and multivariate logistic regression, showed a significant and independent correlation with pSS diagnosis (p value <0.05). No correlation was found between SGdS semi-quantitative parameters and ESSDAI. The proposed nomogram accuracy was 87%. CONCLUSION: SGdS is an accurate and reproducible tool for the diagnosis of pSS. ESSDAI was not shown to be correlated with SGdS data. CLINICAL RELEVANCE: SGdS should be the first-line imaging technique in patients with suspected pSS.

Accuracy of the automated cell counters for management of spontaneous bacterial peritonitis.

AIM: To evaluate the accuracy of automated blood cell counters for ascitic polymorphonuclear (PMN) determination for: (1) diagnosis, (2) efficacy of the ongoing antibiotic therapy, and (3) resolution of spontaneous bacterial peritonitis (SBP). METHODS: One hundred and twelve ascitic fluid samples were collected from 52 consecutive cirrhotic patients, 16 of them with SBP. The agreement between the manual and the automated method for PMN count was assessed. The sensitivity/specificity and the positive/negative predictive value of the automated blood cell counter were also calculated by considering the manual method as the "gold standard". RESULTS: The mean +/- SD of the difference between manual and automated measurements was 7.8 +/- 58 cells/mm(3), while the limits of agreement were +124 cells/mm(3) [95% confidence interval (CI): +145 to +103] and -108 cells/mm(3) (95% CI: -87 to -129). The automated cell counter had a sensitivity of 100% and a specificity of 97.7% in diagnosing SBP, and a sensitivity of 91% and a specificity of 100% for the efficacy of the ongoing antibiotic therapy. The two methods showed a complete agreement for the resolution of infection. CONCLUSION: Automated cell counters not only have a good diagnostic accuracy, but are also very effective in monitoring the antibiotic treatment in patients with SBP. Because of their quicker performance, they should replace the manual counting for PMN determination in the ascitic fluid of patients with SBP.

Efficacy of current guidelines for the treatment of spontaneous bacterial peritonitis in the clinical practice.

AIM: To verify the validity of the International Ascites Club guidelines for treatment of spontaneous bacterial peritonitis (SBP) in clinical practice. METHODS: All SBP episodes occurring in a group of consecutive cirrhotics were managed accordingly and included in the study. SBP was diagnosed when the ascitic fluid polymorphonuclear (PMN) cell count was > 250 cells/mm3, and empirically treated with cefotaxime. RESULTS: Thirty-eight SBP episodes occurred in 32 cirrhotics (22 men/10 women; mean age: 58.6 +/- 11.2 years). Prevalence of SBP, in our population, was 17%. Ascitic fluid culture was positive in nine (24%) cases only. Eleven episodes were nosocomial and 71% community-acquired. Treatment with cefotaxime was successful in 59% of cases, while 41% of episodes required a modification of the initial antibiotic therapy because of a less-than 25% decrease in ascitic PMN count at 48 h. Change of antibiotic therapy led to the resolution of infection in 87% of episodes. Among the cases with positive culture, the initial antibiotic therapy with cefotaxime failed at a percentage (44%) similar to that of the whole series. In these cases, the isolated organisms were either resistant or with an inherent insufficient susceptibility to cefotaxime. CONCLUSION: In clinical practice, ascitic PMN count is a valid tool for starting a prompt antibiotic treatment and evaluating its efficacy. The initial treatment with cefotaxime failed more frequently than expected. An increase in healthcare-related infections with antibiotic-resistant pathogens may explain this finding. A different first-line antibiotic treatment should be investigated.