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.

Three-dimensional Virtual Models' Assistance During Minimally Invasive Partial Nephrectomy Minimizes the Impairment of Kidney Function.

Three-dimensional virtual models (3DVMs) are nowadays under scrutiny to improve partial nephrectomy (PN) outcomes. This report aims to analyze their impact on renal function preservation after minimally invasive PN. A total of 100 patients treated with minimally invasive PN with contrast-enhanced computed tomography from which a 3DVM was obtained, and having undergone baseline and 3rd month postoperative renal scans were prospectively enrolled and compared with a control group of 251 patients without 3DVMs. Weighted differential of pre- and postoperative renal scan-based effective renal plasmatic flow (b-WD ERPF) was calculated, according to the availability of 3DVMs and PADUA risk category. Multivariable logistic regression (MLR) models predicting a significant loss of renal function (LORF; ERPF drop >20%) were performed, overall and according to PADUA risk categories. The b-WD ERPF of the 3DVM group showed significantly lower LORF (-10%) than that of the control group (-19.6%, p = 0.02). In MLR, the availability of a 3DVM was found to be the only protective factor against a significant LORF (odds ratio [OR] = 0.3, p = 0.002). Moreover, after stratification as per tumor surgical complexity, this protective role was observed in both PADUA 8-9 and ≥10 category risk patients (OR = 0.3, p = 0.03 and OR = 0.1, p = 0.01). PATIENT SUMMARY: The drop in operated kidney function was significantly lower in surgeries assisted by three-dimensional virtual models (3VDMs), indicating that the availability of a 3VDM is the only protective factor against a significant functional damage.

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.

Evaluation of functional outcomes after laparoscopic partial nephrectomy using renal scintigraphy: clamped vs clampless technique.

OBJECTIVES: To examine differences in postoperative renal functional outcomes when comparing clampless with conventional laparoscopic partial nephrectomy (LPN) by using renal scintigraphy, and to identify the predictors of poorer postoperative renal functional outcomes after clampless LPN. PATIENTS AND METHODS: Between September 2010 and September 2012, 87 patients with renal masses suitable for LPN were prospectively enrolled in the study. From September 2010 to September 2011, LPN with renal artery clamping was performed and from September 2011 to September 2012 clampless LPN (no clamping of renal artery) was performed. Patients who underwent clampless LPN were unselected and consecutive, and the procedure was performed at the end of surgeon's learning curve. Patients were divided into two groups according to warm ischaemia time (WIT): group A, conventional LPN and group B, clampless-LPN (WIT = 0 min). Demographic and peri-operative data were collected and analysed and functional outcomes were evaluated using biochemical markers and renal scintigraphy at baseline and at 3 months after surgery. The percentage loss of renal function, evaluated according to renal scintigraphy, was calculated. Chi-squared and Student's t-tests were carried out and regression analysis was performed. RESULTS: Group A was found to be similar to group B in all variables measured except for WIT and blood loss (P < 0.001). The percentage reduction in renal scintigraphy values was not significantly different between the groups (reductions of 5% in group A and 6% in group B for split renal function [SRF] and 12% in group A and 17% in group B for estimated renal plasmatic flow [ERPF]; P = 0.587 and P = 0.083, respectively). Multivariate analysis in group B showed that the lower the baseline values of SRF and ERPF, the poorer the postoperative functional outcome of the treated kidney. CONCLUSIONS: In our experience, even clampless LPN was not found to be functionally harmless. The patients who benefitted most from a clampless approach were those with the poorest baseline renal function.

Long-term functional evaluation of the treated kidney in a prospective series of patients who underwent laparoscopic partial nephrectomy for small renal tumors.

BACKGROUND: Renal scintigraphy may allow long-term monitoring of ischemic damage after partial nephrectomy (PN). OBJECTIVE: Evaluate use of renal scintigraphy for evaluating long-term effects of warm ischemia on renal function in patients with a normal contralateral kidney. DESIGN, SETTING, AND PARTICIPANTS: We prospectively examined kidney function of 54 patients who underwent laparoscopic PN (LPN). Minimum follow-up time was 4 yr. INTERVENTION: LPN was performed with warm ischemia by transperitoneal or retroperitoneal approach. MEASUREMENTS: Demographic, perioperative, and pathologic data and postoperative complications were registered. Split renal function (SRF) and effective renal plasma flow (ERPF) were evaluated by renal scintigraphy preoperatively, at 3 and 12 mo postoperatively, then yearly. Baseline weighted differentials (b-WDs) of both SRF and ERPF in the affected kidney were calculated between baseline condition and every time point. Multivariate linear regression was used to find independent variables for increased b-WDs at 3 and 48 mo. P values<0.05 were considered significant. RESULTS AND LIMITATIONS: The SRF and ERPF of kidneys treated by LPN decreased significantly at month 3 and subsequently remained stable through the duration of follow-up. Conversely, neither serum creatinine nor estimated glomerular filtration rate changed significantly during follow-up. The regression model showed statistical significance at month 3 for warm ischemia time (WIT) and age, whereas at 48 mo, statistical significance was reached by WIT alone. No new onset of cardiovascular disease was registered. No evidence of local recurrence was recorded with computed tomography scan. Our study may be underpowered due to small sample size; however, this is one of the largest long-term prospective series using renal scintigraphy to evaluate the renal function after LPN. CONCLUSIONS: WIT contributes to irreversible kidney damage observed at month 3 that does not appear to worsen.

The effects of warm ischaemia time on renal function after laparoscopic partial nephrectomy in patients with normal contralateral kidney.

PURPOSE: To assess the effects of warm ischaemia time (WIT) on renal function after laparoscopic partial nephrectomy (LPN) for renal masses in patients with a normal contralateral kidney. METHODS: From October 2006 to December 2008, 53 patients treated with LPN were enrolled in this prospective study. Effective renal plasma flow (ERPF) was estimated with 99mTc-mercaptoacetyltriglycine renal scintigraphy before the intervention and after 3 and 12 months. Multiple linear regression analysis was used to assess the effects of demographic and operative variables on postoperative renal function. Logistic regression analysis was used to evaluate the associations between the same variables and a ≥20% reduction in postoperative ERPF compared with baseline (defined as significant loss of renal function-LRF). ROC curve analysis was used to identify potential ischaemia time cut-off points. RESULTS: Fifty-one patients were eligible. The mean lesion size was 30 mm, and the mean WIT was 21.9 min. Longer WIT was associated with lower postoperative ERPF values (P < 0.001). A logistic regression model confirmed that longer WITs were significantly associated with ERPF decreases ≥20% (OR 1.454 and 1.741, for each 1-min increase, respectively). ROC analysis identified 25 min as a 'safe' cut-off for WIT (AUC 0.874, P < 0.001). Postoperative ERPF differences between the two groups (WIT ≤25 and >25 min) were significant. CONCLUSIONS: Longer WIT was associated with LRF, as estimated with renal scintigraphy. LRF occurred within 3 months and remains stable until the 12th month after LPN. Every effort should be made to minimise warm ischaemic intervals during LPN, and the limit of 25 min should be not exceeded.

99mTc-MIBI Imaging in the presurgical characterization of thyroid follicular neoplasms: relationship to multidrug resistance protein expression.

UNLABELLED: Recently, thyroid (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintiscanning has been proposed in an attempt to preoperatively identify thyroid malignancies, but discrepant results have been reported for oncocytic lesions. The aim of this study was to investigate the usefulness of visual and semiquantitative analyses of (99m)Tc-MIBI scintigraphy for preoperatively characterizing thyroid nodules with indeterminate cytologic diagnoses, segregating in advance nononcocytic variants from those that are oncocytic. This study also aimed to analyze the relationship between (99m)Tc-MIBI images and P-glycoprotein (P-gp)/multidrug resistance-associated protein-1 (MRP1) immunohistochemical expression. METHODS: Fifty-one consecutive patients with cold thyroid nodules cytologically diagnosed as nononcocytic or oncocytic follicular neoplasm were prospectively studied. Visual and semiquantitative (99m)Tc-MIBI scanning was performed and the diagnoses of the lesions were histologically proven by subsequent thyroidectomy. Immunohistochemical evaluation of P-gp and MRP1 was also performed on surgical samples. RESULTS: Visual and semiquantitative (99m)Tc-MIBI scintiscans showed a low specificity in preoperatively discriminating malignant oncocytic lesions. In nononcocytic nodules, the semiquantitative method was more accurate than the visual (94.44% and 77.78%, respectively). P-gp protein expression was negative in all thyroid lesions, whereas apical plasma membrane MRP1 expression was found in 78% of the lesions with a negative (99m)Tc-MIBI retention index, compared with 11% of lesions with a positive retention index, correlating most strongly with a negative (99m)Tc-MIBI RI in those cases with strong MRP1 apical expression. CONCLUSION: Semiquantitative (99m)Tc-MIBI scintigraphy is an adjunctive method to predict preoperatively the malignant behavior of nononcocytic follicular thyroid nodules indeterminate at fine-needle aspiration biopsy, with a potential impact on the definition of their clinical management. Moreover, the good correlation found between immunohistochemical apical expression of MRP1 and the scintigraphic findings supports the (99m)Tc-MIBI results and provides tissue information on the molecular mechanisms responsible for (99m)Tc-MIBI images in thyroid lesions.