BAP1 Loss, Nuclear Grading, and Nonepithelioid Features in the Diagnosis of Mesothelioma in Italy: Nevermore without the Pathology Report.

The pathologic diagnosis of pleural mesothelioma is generally based on international guidelines, but no compulsory points based on different drugs approvals in different European countries are required to be reported. According to the last (2021) edition of the World Health Organization classification of pleural tumors, the nuclear grade of epithelioid-type mesothelioma should be always inserted in the pathologic report, while the presence of BRCA-associated protein-1 (BAP1) (clone C4) loss and a statement on the presence of the sarcomatoid/nonepithelioid component are fundamental for both a screening of patients with suspected BAP1 tumor predisposition syndrome and the eligibility to perform first-line immunotherapy at least in some countries. Several Italian experts on pleural mesothelioma who are deeply involved in national scientific societies or dedicated working groups supported by patient associations agreed that the pathology report of mesothelioma of the pleura should always include the nuclear grade in the epithelioid histology, which is an overt statement on the presence of sarcomatoid components (at least 1%, in agreement with the last classification of pleural mesothelioma) and the presence of BAP1 loss (BAP1-deficient mesothelioma) or not (BAP1-retained mesothelioma) in order to screen patients possibly harboring BAP1 tumor predisposition syndrome. This review aims to summarize the most recent data on these three important elements to provide evidence regarding the possible precision needs for mesothelioma.

Management of patients with extensive small-cell lung cancer in the immunotherapy era: An Italian consensus through a Delphi approach.

BACKGROUND: Immunotherapy represented a turning point for treating extensive small-cell lung cancer (ES-SCLC). Although, many issues remain debated. METHODS: A group of Italian medical and radiation oncologists with expertise in managing patients with ES-SCLC developed a list of statements divided in six areas of interest. The Delphi method was used to assess the consensus on the defined list of statements. RESULTS: 32 statements were included in the final list to be voted by the Delphi panel, and 26 reached a consensus on the agreement. A prompt involvement of a multidisciplinary team is a priority to provide an integrated treatment strategy. First-line recommended treatment is immunotherapy in combination with platinum-based chemotherapy and etoposide for four cycles followed by maintenance immunotherapy. CONCLUSIONS: While awaiting new data from clinical trials and real-world studies, these recommendations can represent a useful tool to guide the management of ES-SCLC patients in daily practice.

Evaluation of RADIANCE Monte Carlo algorithm for treatment planning in electron based Intraoperative Radiotherapy (IOERT).

PURPOSE: To perform experimental as well as independent Monte Carlo (MC) evaluation of the MC algorithm implemented in RADIANCE version 4.0.8, a dedicated treatment planning system (TPS) for 3D electron dose calculations in intraoperative radiation therapy (IOERT). METHODS AND MATERIALS: The MOBETRON 2000 (IntraOp Medical Corporation, Sunnyvale, CA) IOERT accelerator was employed. PDD and profiles for five cylindrical plastic applicators with 50-90 mm diameter and 0°, 30° beveling were measured in a water phantom, at nominal energies of 6, 9 and 12 MeV. Additional PDD measurements were performed for all the energies without applicator. MC modeling of the MOBETRON was performed with the user code BEAMnrc and egs_chamber of the MC simulation toolkit EGSnrc. The generated phase space files of the two 0°-bevel applicators (50 mm, 80 mm) and three energies in both RADIANCE and BEAMnrc, were used to determine PDD and profiles in various set-ups of virtual water phantoms with air and bone inhomogeneities. 3D dose distributions were also calculated in image data sets of an anthropomorphic tissue-equivalent pelvis phantom. Image acquisitions were realized with a CT scanner (Philips Big Bore CT, Netherlands). Gamma analysis was applied to quantify the deviations of the RADIANCE calculations to the measurements and EGSnrc calculations. Gamma criteria normalized to the global maximum were investigated between 2%, 2 mm and 3%, 3 mm. RESULTS: RADIANCE MC calculations satisfied the gamma criteria of 3%, 3 mm with a tolerance limit of 85% passing rate compared to in- water phantom measurements, except for the dose profiles of the 30° beveled applicators. Mismatches lay in surface doses, in umbra regions and in the beveled end of the 30° applicators. A very good agreement to the EGSnrc calculations in heterogeneous media was observed. Deviations were more pronounced for the larger applicator diameter and higher electron energy. In 3D dose comparisons in the anthropomorphic phantom, gamma passing rates were higher than 96 % for both simulated applicators. CONCLUSIONS: RADIANCE MC algorithm agrees within 3%, 3 mm criteria with in-water phantom measurements and EGSnrc MC dose distributions in heterogeneous media for 0°-bevel applicators. The user should be aware of missing scattering components and the 30° beveled applicators should be used with attention.

Non-Small Cell Lung Cancer Testing on Reference Specimens: An Italian Multicenter Experience.

INTRODUCTION: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. METHODS: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. RESULTS: Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. CONCLUSIONS: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.

Evaluation of a Novel Fixative Solution for Liquid-Based Cytology in Diagnostic Cytopathology.

Since its introduction in the early 2000s, liquid-based cytology (LBC) has been increasingly used for gynecologic and non-gynecologic cytology, and its multiple advantages have been widely recognized. The aim of this study was to investigate the use of a new fixative and pre-analytical method for morphological diagnosis in cytological samples. In particular, we evaluated the effect of a novel preservative solution on the preparation of diagnostic slides by comparing it with the standard reference used globally in cytology laboratories. This study included both gynecological (n = 139) and non-gynecological (n = 183) samples. Several morphologic variables were then identified and evaluated. Using this approach, we were then able to demonstrate the suitability of the new system, with improved safety, to be integrated within current pathology clinical practice. Overall, using a safer preservative solution, the study shows no statistical difference (and then non-inferiority) in the new fixation protocol compared with the standard reference used in routine practice in terms of diagnostic adequacy, evaluated both in clinically relevant gyn and non-gyn datasets.