Prostate-specific membrane antigen-PET/CT may result in stage migration in prostate cancer: performances, quantitative analysis, and potential criticism in the clinical practice.

AIM: The early detection of prostate cancer (PCa) metastatic disease with PET imaging leads to stage migration and change of disease management. We aimed to assess the impact on clinical management deriving from prostate-specific membrane antigen (PSMA) imaging with a digital PET/CT during the routine application in the staging and restaging process of PCa. MATERIAL AND METHODS: Eighty consecutive PCa patients underwent 18F-PSMA-1007. Digital PET/CT were retrospectively evaluated and discussed with oncologists to evaluate the impact on clinical management. Performances analysis, correlation among variables also considering semiquantitative parameters have been conducted. RESULTS: In the whole group of 80 patients at staging (N = 31) and restaging (N = 49), the detection rate of PSMA PET was 85% for all lesions. At staging, the performance analysis resulted in sensitivity 77.6%, specificity 89.5%, negative predictive value (NPV) 77.6%, positive predictive value (PPV) 89.5%, accuracy 85.7%, and area under curve (AUC) 0.87%. The performance of restaging PET in the group of patients with PSA values <1 ng/ml resulted in the following values: sensitivity 66.7%, specificity 92.9%, NPV 85.7%, PPV 81.3%, accuracy 82.6%, and AUC 0.79. Semiquantitative analysis revealed a mean value of SUVmax, metabolic tumor volume, and total lesion PSMA expression with differences in patients with high risk compared to low intermediate. At restaging PET, semiquantitative values of patients with total prostate specific antigen (tPSA) ≤ 1 ng/ml were significantly less than those of the tPSA > 1 ng/ml. A significant impact on clinical management was reported in 46/80 patients (57.5%) based on PSMA PET findings at staging and restaging. CONCLUSION: Although PSMA-PET provides optimal performances, its current role in redefining a better staging should be translated in the current clinical scenario about potential improvement in clinical/survival outcomes.

Cerebellum and cognition in progressive MS patients: functional changes beyond atrophy?

BACKGROUND: The cerebellum is a predilection site of pathology in progressive multiple sclerosis (PMS) patients, contributing to cognitive deficits. Aim of this study was to investigate lobular cerebellar functional connectivity (FC) in PMS patients in relation to cognition. METHODS: In this cross-sectional study, resting state fMRI analysis was carried out on 29 PMS patients (11 males, mean age 51.2 ± 11.9 years) and 22 age- and sex-matched healthy controls (HC) (11 males, mean age 49.6 ± 8.8 years). Data were analyzed with a seed-based approach, with four different seeds placed at the level of cerebellar Lobule VI, Crus I, Crus II and Lobule VIIb, accounting for cerebellar structural damage. Cognitive status was assessed with the BICAMS battery. Correlations between fMRI data and clinical variables were probed with the Spearman correlation coefficient. RESULTS: When testing FC differences between PMS and HC without taking into account cerebellar structural damage, PMS patients showed a reduction of FC between Crus II/Lobule VIIb and the right frontal pole (p = 0.001 and p = 0.002, respectively), with an increased FC between Lobule VIIb and the right precentral gyrus (p < 0.001). After controlling for structural damage, PMS patients still showed a reduced FC between Crus II and right frontal pole (p = 0.005), as well as an increased FC between Lobule VIIb and right precentral gyrus (p = 0.003), with the latter showing an inverse correlation with BVMT scores (r = - 0.393; p = 0.03). CONCLUSION: PMS patients show cerebellar FC rearrangements that are partially independent from cerebellar structural damage, and are likely expression of a maladaptive functional rewiring.

Treatment with abiraterone in metastatic castration-resistant prostate cancer patients progressing after docetaxel: a retrospective study.

The aim of this study was to evaluate abiraterone's efficacy in Italian patients affected with metastatic prostate cancer progressing after treatment with docetaxel. We conducted a retrospective analysis of 60 patients. Prostate-specific antigen (PSA) reduction in serum was the primary endpoint for evaluating the efficacy of abiraterone in combination with prednisone treatment, whereas reduced pain, safety, progression-free survival, response rate, and overall survival (OS) were secondary endpoints. A significant correlation was noticed between PSA response and OS. Further, the Index Bravais-Pearson (r) correlation allowed us to observe a significant negative interdependence between PSA response and reduction in pain of 0.57 (95% confidence interval: -0.30 to 0.80) (P=0.005). Meanwhile, regression analysis revealed that PSA levels are predictive of OS. There was a positive correlation with OS, which showed a value of R to 0.50 with a slope of 1.44 (P=0.0021). Abiraterone is a well-tolerated and effective treatment modality for patients affected with metastatic castration-resistant prostate cancer. The drug has a better tolerability profile, gives significant pain relief, and increases the survival rate.

Transcutaneous Vagus Nerve Stimulation Combined with Robotic Rehabilitation Improves Upper Limb Function after Stroke.

The efficacy of standard rehabilitative therapy for improving upper limb functions after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) paired with rehabilitation is a promising approach, but the invasiveness of this technique limits its clinical application. Recently, a noninvasive method to stimulate vagus nerve has been developed. The aim of the present study was to explore whether noninvasive VNS combined with robotic rehabilitation can enhance upper limb functionality in chronic stroke. Safety and efficacy of this combination have been assessed within a proof-of-principle, double-blind, semirandomized, sham-controlled trial. Fourteen patients with either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted therapy associated with real or sham VNS, delivered for 10 working days. Efficacy was evaluated by change in upper extremity Fugl-Meyer score. After intervention, there were no adverse events and Fugl-Meyer scores were significantly better in the real group compared to the sham group. Our pilot study confirms that VNS is feasible in stroke patients and can produce a slight clinical improvement in association to robotic rehabilitation. Compared to traditional stimulation, noninvasive VNS seems to be safer and more tolerable. Further studies are needed to confirm the efficacy of this innovative approach.

Weekly pegylated liposomal doxorubicin and paclitaxel in patients with metastatic breast carcinoma: A phase II study.

Pegylated liposomal doxorubicin (PLD) has the advantage of delivering active anthracycline directly to the tumor site, while exposing the patient to a lesser degree of doxorubicin-associated toxicities. Recently, a regimen in which paclitaxel is infused weekly over 1 h produced substantial antitumor activity with little myelosuppression. We designed a phase II trial to study the efficacy and toxicity of 10 mg/m(2) PLD on Days 1, 8 and 15, plus 70 mg/m(2) paclitaxel weekly in patients with untreated metastatic breast cancer and a high risk of cardiotoxicity. The study included 35 patients, with 31 (88.5%) evaluable for efficacy and 35 (100%) for toxicity. A total of 28 patients (80%) had two or more sites of disease. Overall, 4 complete and 16 partial responses were noted with an overall response rate of 64.5%, with 6 cases of stable and 5 cases of progressive disease. Toxicity was found to be manageable in that the only grade 3-4 side effects recorded were palmar-plantar erythrodysesthesia, 8.5%; mucositis, 2.8%; leucopenia, 12.5%; anemia, 2.8% and AST/ALT, 2.8%. No cardiotoxicity was observed. In conclusion, weekly PLD plus paclitaxel appears to be a well-tolerated and effective approach for metastatic breast cancer patients with a high risk of cardiotoxicity.

Docetaxel and gemcitabine in the treatment of metastatic breast carcinoma: a dose finding study.

AIMS AND BACKGROUND: Patients with metastatic breast cancer previously treated with anthracyclines for advanced disease are usually refractory to any further treatment with anthracyclines and have a poor prognosis. Therefore, new drugs or new combinations of drugs are needed. One approach has been to focus on the type of chemotherapy with low toxicity that preserves quality of life during treatment, such as weekly drug administration. STUDY DESIGN: We designed a dose-finding study to determine the maximum tolerated dose of gemcitabine plus docetaxel, given on a weekly schedule in metastatic breast cancer previously treated with anthracyclines. Three escalating doses of gemcitabine (900, 1000 and 1100 mg/m2) on days 1 and 8 in combination with a fixed dose of docetaxel, 35 mg/m2 on days 1 and 8 were planned. Dose-limiting toxicity included grade > 3 hematologic toxicity, grade > 2 stomatitis, asthenia, diarrhea or organ-specific toxicity (except alopecia). Dose escalation was stopped if 1 out of 3 patients at any dose level experienced dose-limiting toxicity. RESULTS: Nine patients received a mean of 5.1 (range, 1-9) cycles. Gastrointestinal and leukopenia were the main dose-limiting toxicity. No patient experienced dose-limiting toxicity at dose level 1; at dose level 2, 2 out of 3 patients had dose-limiting toxicity and 3 additional patients treated at dose level 2 confirmed that the maximum tolerated dose had been reached. CONCLUSIONS: The recommended gemcitabine dose in combination with docetaxel (35 mg/m2 for a phase II study) was established at 900 mg/m2.

[Reports on nine cases of spondylodiscitis]. / Osservazioni su nove casi di spondilodiscite.

Spondylodiscitis is an infection of the intervertebral disk and the adjacent vertebrae, with or without associated epidural or psoas abscesses. It is a serious disease both due to its long-term course and the possible outcomes. It is frequently caused by S. aureus and, in endemic areas, by Mycobacterium tuberculosis and Brucella spp. We describe 9 cases, from October 2004 to August 2005, all spontaneous diseases occurring in adults (mean age 64 years). The site of infection was lumbar in 7, lumbar-sacral in 1 and dorsal in 1. None were associated to sepsis. The causative bacteria were known in 6 cases (1 BK, 1 S. aureus, 4 Brucella) and unknown in 3 cases. In all cases therapy was only medical. Significant circulation in Sicily of both Mycobacterium tuberculosis and Brucella spp. make those microorganisms the most frequent agents of spondylodiscitis.

Treatment of metastatic breast cancer with vinorelbine and docetaxel.

OBJECTIVE: A phase II study was performed to evaluate efficacy and safety of the combination vinorelbine and docetaxel in patients with metastatic breast cancer previously treated with anthracycline-based regimens. Overall 41 patients were included in the study. METHODS: Treatment consisted of vinorelbine 25 mg/m2 and docetaxel 75 mg/m2, both administered on day 1 every 3 weeks for a maximum of 9 cycles. Most patients (92%) were postmenopausal with a median age of 57 years, and median ECOG performance of 1. Sites of disease were viscera in 42% of patients, bones in 30%, soft-tissues in 32%. Sixty-five percent of patients had >2 metastatic sites. Previous treatments included neo-adjuvant chemotherapy in 7.3% of cases, adjuvant chemotherapy in 71%, and front-line chemotherapy for advanced disease in 50% of cases. RESULTS: A total of 273 cycles of chemotherapy were delivered (mean 6 cycles/patient). All patients were assessable for toxicity: alopecia was recorded in all patients, grade 2-3 neutropenia in 34% and grade 4 in 9.7%; grade 2-3 nausea/vomiting in 29%, grade 2-3 mucositis in 24.3%. Out of 39 patients evaluable for response, 7 (18%) complete responses and 13 (33%) partial responses have been recorded with an overall response rate of 51%. Six patients (15%) experienced stable disease and 13 patients (33%) progressed. Mean duration of responses was 15.2 months. Median time to progression and median overall survival were 6.2 and 14 months, respectively. CONCLUSION: In patients with metastatic breast cancer previously treated with anthracyclines the combination vinorelbine-docetaxel is very active and well tolerated representing a valid therapeutic option for the management of this patient population.

Chemotherapy with cisplatin and 5-fluorouracil chronomodulated infusion in locally advanced or metastatic/recurrent carcinoma of the cervix.

AIMS AND BACKGROUND: The purpose of this study was to review our experience with the combination of circadian chronomodulated 5-fluorouracil infusion in association with cisplatin in patients with locally advanced or metastatic cancer of the cervix in order to assess the activity and tolerability of the combination. METHODS: Twenty patients with locally advanced disease and 21 patients with metastatic or recurrent disease were treated from January 1995 to May 1999. 5-fluorouracil (600 mg/m2, days 1 to 5) was administered by a continuous circadian-shaped infusion employing an external programmable portable pump; cisplatinum (20 mg/m2) was infused days 1 through 5 i.v. over a 2-hr period. Response to treatment was evaluated after 3 and 6 cycles of therapy. Patients with locally advanced disease who achieved a clinical shrinkage of their tumor or were at least stable were submitted to surgery; pelvic radiotherapy was administered to patients with disease progression. RESULTS: Seven patients with locally advanced disease achieved a partial clinical response (overall response, 35%; 95% CI, 15.4-59.2), and 12 of 20 patients were submitted to surgery. Median progression-free and overall survival were 17 months and 36 months, respectively. Objective responses were observed in 9 of 21 patients with metastatic/recurrent disease (7 partial plus 2 minor responses: overall response 43%; 95% CI, 21.8-65.9). Median time to progression and overall survival were 5 and 17 months, respectively. CONCLUSIONS: Cisplatinum plus 5-fluorouracil chronomodulated infusion showed a moderate but definite activity and was well tolerated in both groups of patients. In consideration of clinical results comparable to more toxic and expensive regimens reported in the literature, the combination appears to be a reasonable option especially for women with metastatic/recurrent cervical carcinoma and a promising treatment in combination with definitive radiotherapy in patients with locally advanced disease.