Purpose: NGR-hTNF exploits the tumor-homing peptide asparagine-glycine-arginine (NGR) for selectively targeting TNF-a to an aminopeptidase N overexpressed on cancer endothelial cells. Preclinical synergism with cisplatin was displayed even at low doses. This study primarily aimed to explore the safety of low-dose NGR-hTNF combined with cisplatin in resistant/refractory malignancies. Secondary aims included pharmacokinetics (PKs), pharmacodynamics, and activity.Experimental Design: NGR-hTNF was escalated using a doubling-dose scheme (0.2-0.4-0.8-1.6 mg/m 2 ) in combination with fixed-dose of cisplatin (80 mg/m 2 ), both given intravenously once every three weeks. PKs and circulating TNF-receptors (sTNF-Rs) were assessed over the first three cycles.Results: Globally, 22 patients (12 pretreated with platinum) received a range of one to ten cycles. Consistently with the low-dose range tested, maximum-tolerated dose was not reached. No dose-limiting toxicities (DLTs) were observed at 0.2 (n ¼ 4) and 0.4 mg/m 2 (n ¼ 3). One DLT (grade 3 infusion-related reaction) was observed at 0.8 mg/m 2 . This dose cohort was expanded to six patients without further DLTs.No DLTs were noted also at 1.6 mg/m 2 (n ¼ 3). NGR-hTNF exposure increased dose-proportionally without apparent PK interactions with cisplatin. No shedding of sTNF-Rs was detected up to 0.8 mg/m 2 . At the dose level of 0.8 mg/m 2 , expanded to 12 patients for activity assessment, a platinum-pretreated lung cancer patient achieved a partial response lasting more than six months and five patients maintained stable disease for a median time of 5.9 months.Conclusions: The combination of NGR-hTNF 0.8 mg/m 2 with cisplatin 80 mg/m 2 showed favorable toxicity profile and promising antitumor activity.

Clerical errors occurring during specimen collection, issue and transfusion of blood are the most common cause of AB0 incompatible transfusions. 40-50% of the transfusion fatalities result from errors in properly identifying the patient or the blood components. The frequency and type of errors observed, despite the implementation of measures to prevent them, suggests that errors are inevitable unless major changes in procedures are adopted. A fail-safe system, which physically prevents the possibility of error, was adopted in January 1993 and concurrently a quality improvement program was implemented to monitor any transfusion errors. Up to December 1994, 10,995 blood units (5,057 autologous and 5,938 allogeneic) were transfused to 3,231 patients. Seventy-one methodological errors(1/155 units) were observed, half of which were concentrated during the first 4 months of introducing the system. However the system detected and avoided four potentially fatal errors (1/2,748 units). Two cases involved the interchanging of recipient sample tubes, 1 case was due to patient misidentification and the other involved misidentification of blood units. In conclusion the system is effective in detecting otherwise undiscovered errors in transfusion practice and can prevent potential transfusion-associated fatalities caused by misidentification of blood units or recipients.

Background: Recently, new evidence of the next-generation sequencing (NGS) liquid biopsy utility in clinical practice has been developed. This assay is emerging as a new promising tool to use as a noninvasive biomarker for cancer mutation profiling. Additional data supporting the clinical validity of cell free DNA (cfDNA) based testing is necessary to inform optimal use of these assays in the clinic. Materials and methods: A total of 398 cancer patients were analyzed by FoundationOne Liquid Analysis (F1LA), a genomic profiling assay and by standard NGS diagnostic ThermoFisher platform. The association between diagnostic technique was evaluated using a Poisson regression model. FoundationOne Liquid (F1L) and FoundationOne Liquid CDx (F1LCDx) detect 70 and 324 cancer-related genes alterations, respectively, including genomic signatures tumor fraction, blood tumor mutational burden (only for the 324 genes version), and microsatellite instability high status. Both assays used a single DNA extraction method to obtain cfDNA. The real-life clinical impact and feasibility of F1L and F1LCDx were evaluated across different solid tumors in our department. Results: Between 1 January 2019 and 28 February 2021, 398 samples of different tumor types from 398 patients were analyzed (overall success rate: 92%, in FoundationOne Liquid CDx Analysis success rate: 97%). Most frequent molecular alterations were TP53 (74), APC (40), DNMT3A (39), KRAS (23). The comprehensive clinical impact of F1LA compared with standard diagnostic was 64.7% versus 22.1% [risk ratio (RR) = 2.94; p < 0.001] and the potential clinical impact was 58.6% versus 11.0% (RR = 5.32; p < 0.001), respectively. Furthermore, some clinical cases were selected, in which F1LA detected actionable alterations offering an unexpected therapeutic choice. Conclusions: Although additional studies are needed to better select patients and setting, NGS F1LA is a useful, noninvasive, and repeatable assay to guide therapeutic choice in oncology. It provides a snapshot of cancer heterogeneity profile that could be incorporated in routinely clinical practice.

Background: In advanced colorectal cancer (ACC), FOLFOX4 has been accepted as a standard chemotherapeutic regimen. Due to the neurotoxicity induced by oxaliplatin, which occurs in about 50% of patients during the 6-month FOLFOX4 regimen, and the frequent need for hospitalization, alternative regimens may be required. We aimed to determine whether a ‘maintenance’ therapy with oral UFT (uracil-tegafur) in patients responding to FOLFOX4 is able to maintain the response and improve the quality of life (QoL) as a result of the outpatient regimen and lower psychological distress. Methods: Untreated patients with ACC who did not progress after 6 months of FOLFOX4 received oral UFT until disease progression or unacceptable toxicity. The aim of the study was to maintain the response obtained with the FOLFOX4 regimen for at least 6 months. The secondary objective was to evaluate QoL during the two different treatment regimens utilizing the 36-item Short Form Health Survey (SF-36). Results: From January 2003 to August 2004, out of the enrolled 30 patients [22 males and 8 females; 2 patients with a complete response (CR), 14 patients with a partial response (PR) and 6 patients in stable disease (SD) after 6 months of FOLFOX4] 22 continued therapy with UFT until progression without significant toxicity; the remaining 8 patients (27%) had progressive disease (PD) during or at the end of FOLFOX4 and were treated with other regimen. After 6 months of UFT, 4 patients (13%) had CR, 6 patients (20%) PR and 4 patients (13%) SD; 16 patients (53%) progressed. Median follow-up was 31 months [interquartile range (IQR): 20–31 months]; 14 patients died of PD. The median time to progression was 13.9 (IQR: 7.7–20.1) months and the median survival time was 31 months (IQR: 20–31 months). Evaluation of QoL demonstrated a trend towards better QoL during UFT treatment. Conclusions: These results support the feasibility of maintaining good response and improving QoL (measured by SF-36) with an oral fluoropyrimidine after combination chemotherapy in ACC patients; moreover, since UFT can be used orally, patient compliance is increased and the duration of hospitalization can be decreased.