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Background: Pleural mesothelioma is a rare cancer with a dismal prognosis and few therapeutic options, especially in the pretreated setting. Immunotherapy with checkpoint inhibitors as single agents yielded interesting results in refractory pleural mesothelioma, achieving a response rate between 10-20%, median progression-free survival of 2-5 months and median overall survival of 7-13 months., Patients and Methods: A retrospective, multi-institutional study of pleural mesothelioma patients treated with nivolumab in second and further line was performed. The endpoints of the study are response rate, disease control rate, progression free survival and overall survival., Results: Sixty-five patients with pleural mesothelioma treated with nivolumab in second and further line were enrolled at seven Italian institutions. The response rate was 8%, disease control rate was 37%, median progression free survival was 5.7 months (95% CI: 2.9-9.0) and median overall survival was 11.1 (95% CI 6.2-19.9) months. A higher neutrophils and neutrophils to lymphocytes ratio at baseline were associated with worse prognosis., Conclusion: Nivolumab as a single agent is fairly active in a cohort of unselected pretreated pleural mesothelioma patients. Further investigations on clinical and translational factors are needed to define which patient might benefit most from nivolumab treatment in pleural mesothelioma., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pleural mesothelioma usually presents at an advanced, incurable stage. Chemotherapy with platinum-pemetrexed is a standard treatment. We hypothesised that the addition of pembrolizumab to platinum-pemetrexed would improve overall survival in patients with pleural mesothelioma., Methods: We did this open-label, international, randomised phase 3 trial at 51 hospitals in Canada, Italy, and France. Eligible participants were aged 18 years or older, with previously untreated advanced pleural mesothelioma, with an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) to intravenous chemotherapy (cisplatin [75 mg/m 2 ] or carboplatin [area under the concentration-time curve 5-6 mg/mL per min] with pemetrexed 500 mg/m 2 , every 3 weeks for up to 6 cycles), with or without intravenous pembrolizumab 200 mg every 3 weeks (up to 2 years). The primary endpoint was overall survival in all randomly assigned patients; safety was assessed in all randomly assigned patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02784171, and is closed to accrual., Findings: Between Jan 31, 2017, and Sept 4, 2020, 440 patients were enrolled and randomly assigned to chemotherapy alone (n=218) or chemotherapy with pembrolizumab (n=222). 333 (76 %) of patients were male, 347 (79%) were White, and median age was 71 years (IQR 66-75). At final analysis (database lock Dec 15, 2022), with a median follow-up of 16·2 months (IQR 8·3-27·8), overall survival was significantly longer with pembrolizumab (median overall survival 17·3 months [95% CI 14·4-21·3] with pembrolizumab vs 16·1 months [13·1-18·2] with chemotherapy alone, hazard ratio for death 0·79; 95% CI 0·64-0·98, two-sided p=0·0324). 3-year overall survival rate was 25% (95% CI 20-33%) with pembrolizumab and 17% (13-24%) with chemotherapy alone. Adverse events related to study treatment of grade 3 or 4 occurred in 60 (27%) of 222 patients in the pembrolizumab group and 32 (15%) of 211 patients in the chemotherapy alone group. Hospital admissions for serious adverse events related to one or more study drugs were reported in 40 (18%) of 222 patients in the pembrolizumab group and 12 (6%) of 211 patients in the chemotherapy alone group. Grade 5 adverse events related to one or more drugs occurred in two patients on the pembrolizumab group and one patient in the chemotherapy alone group., Interpretation: In patients with advanced pleural mesothelioma, the addition of pembrolizumab to standard platinum-pemetrexed chemotherapy was tolerable and resulted in a significant improvement in overall survival. This regimen is a new treatment option for previously untreated advanced pleural mesothelioma., Funding: The Canadian Cancer Society and Merck & Co., Competing Interests: Declaration of interests MP has received grants for research to institution from AstraZeneca and Roche; payment for educational events from Astellas, Pfizer, and AstraZeneca; and received drugs for research from Roche and AstraZeneca. GLR received consulting fees from MSD, BMS, AstraZeneca, Roche, Novartis, Lilly, Amgen, Sanofi, Pfizer, Takeda, GSK, and Italfarmaco; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from MSD, BMS, AstraZeneca, Roche, Novartis, Lilly, Amgen, Sanofi, Pfizer, Takeda, GSK, and Italfarmaco; received support for attending meetings or travel from Roche, MSD, BMS, and Amgen; has participated on a Data Safety Monitoring Board or Advisory Board for MSD, BMS, AstraZeneca, Roche, Novartis, Lilly, Amgen, Sanofi, Pfizer, Takeda, GSK, and Italfarmaco; and has other financial or non-financial interests from MSD, BMS, AstraZeneca, Roche, Novartis, Amgen, Sanofi, Pfizer, Takeda, and GSK. YL holds stock or stock options from Merck. SL received consulting fees from Lilly, MSD, Sanofi, and AbbVie and payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca. AS received grants or contracts (payments to institution) from MSD, BMS, AstraZeneca, Roche, and Amphera; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, BMS, MSD, and Roche; received support for attending meetings or travel from AstraZeneca, BMS, MSD, and Roche; and participated on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, BMS, MSD, and Roche. MF received consulting fees from AstraZeneca, BMS, and Takeda and received honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca, BMS, and Takeda. SAL has participated on a Data Safety Monitoring Board or Advisory Board for Sanofi and Bayer. JRG received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from AstraZeneca and BMS. PB received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Merck and participated on a Data Safety Monitoring Board or Advisory Board for Mirati and AbbVie. NL has received editorial support from EMD Serono; received grants to institute (unrelated) from Amgen, AstraZeneca, Bayer, BMS, Eli Lilly, EMD Serono, Guardant Health, Inivata, Janssen, Merck/MSD, Novartis, Pfizer, Roche, and Takeda; received honoraria or travel funding for CME lectures (unrelated) from AstraZeneca, Beigene, BMS, Janssen, Merck, Novartis, and Takeda; and participated on a Data Safety Monitoring Board or Advisory Board for Mirati, Helsinn, and Daichii Sankyo. LS has received grants or contracts to institution to support clinical trial from AstraZeneca, Merck, Bayer, Novartis, Repare, GSK, and Janssen and holds stock or stock options from AstraZeneca. DED has received research grants from CIHR, CancerCare Manitoba Foundation, and AstraZeneca; received research grants and salary awards from Manitoba Medical Services Foundation; received payment for educational events from Roche, Boehringer Ingelheim, and BMS; served on an advisory board for Merck, AstraZeneca, Pfizer, Jazz Pharmaceuticals, and Novartis; has acted in a leadership or fiduciary role in a board, society, committee or advocacy group, paid or unpaid for Lung Cancer Canada (Medical Advisory Committee), Canadian Association of Medical Oncologists (Chair, Fellowship Committee), and Canadian Cancer Trials Group (Chair, Small Cell Lung Cancer Working Group); and received equipment, materials, drugs, medical writing, gifts, or other services from AstraZeneca (Medical writing assistance on a small-cell lung cancer paper). QC has received grants to institution from Alkermes, Amgen, Apollomics, Astellas, AstraZeneca, Bicycle, BMS, Conjupro, Decipher, Eli Lilly, Esperas, Exactis, GSK, iTEOS, Kelun, Merck, Mirati, Nuvalent, Ocellaris, Pfizer, Rvolution Medicines, Roche, SeaGen, Spectrum, and Treadwell; received consulting fees from Amgen, AnHeart, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GSK, Jazz Pharmaceuticals, Janssen, Merck and Co, Novartis, Pfizer, Roche, and Takeda; received payment for speaking or presentations from AstraZeneca; acted on an advisory board for Amgen, AnHeart, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GSK, Jazz Pharmaceuticals, Janssen, Merck and Co, Novartis, Pfizer, Roche, and Takeda; acted on a Data Safety Monitoring Committee for Merck and KGaA; and occupied a leadership or fiduciary role in a board, society, committee, or advocacy group, paid or unpaid for Lung Cancer Canada and Canadian Mesothelioma Foundation. CWL has served as a member of the Board of Directors for Canadian Mesothelioma Foundation. LG received grants or contracts to institution from BMS, MSD, Takeda, Pfizer, Roche, Amgen, Sanofi, Janssen, Lilly, and Novartis; received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from BMS, MSD, Takeda, Pfizer, Roche, Amgen, Sanofi, Janssen, Lilly, and Novartis; received support for attending meetings or travel from Pfizer, MSD, AstraZeneca, and Takeda; and participated on a Data Safety Monitoring Board or Advisory Board for Inhatarget Therapeutics. XQ received support for attending meetings or travel from Pfizer (ESMO 2022), Janssen (ASCO 2022), and Sanofi (ASCO 2023). VW received consulting fees from Amgen; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bristol Myers Squibb, MSD, Roche, and Sanofi; received support for attending meetings or travel from AstraZeneca, Bristol Myers Squibb, Janssen, MSD, Roche, and Sanofi; and participated on a Data Safety Monitoring Board or Advisory Board for Amgen, AstraZeneca, and Ipsen. GZ received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Inventiva Pharma, Lilly, MSD Oncology, Pfizer, and Roche; acted in a consulting or advisory role for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Da Volterra, Inventiva Pharma, MSD Oncology, Pfizer, and Roche; received research funding from AstraZeneca, Bristol-Myers Squibb, Pfizer, Roche, and Takeda; and received travel, accommodations, and expenses from AbbVie, AstraZeneca, Bristol-Myers Squibb, Lilly, Pfizer, and Roche. MLS received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from BMS and support for attending meetings or travel from Pfizer (ESMO 2022). AM received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Roche, AstraZeneca, BMS, MSD, Pfizer, Takeda, Boehringer, Sanofi, Lilly, Novartis, and Italfarmaco and participated on a Data Safety Monitoring Board or Advisory Board for Roche, AstraZeneca, Pfizer, MSD, and Takeda. FG received consulting fees from Novocure, BMS, Novartis, PharmaMar, Pierre Fabre, and MSD; received payment for speaker bureau from Novocure; received support for attending meetings or travel from Novartis, MSD, BMS, PharmaMar, and Pierre Fabre. SD received payment for presentations from Novartis, Pierre-Fabre, and BMS and travel and accommodation support during meetings from Istituto Gentili, Novartis, Pierre-Fabre, and BMS. GLC received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Novocure and BMS and participated on a Data Safety Monitoring Board or Advisory Board for Novocure. PAZ received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Merck Sharp and Dohme, Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, AstraZeneca, Roche, and Bayer; received support for attending meetings or travel from Merck Sharp and Dohme, Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, AstraZeneca, Roche, and Bayer; and participated on a Data Safety Monitoring Board or Advisory Board for Merck Sharp and Dohme, Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, AstraZeneca, Roche, and Bayer. MM received support for attending meetings or travel from Roche, Pfizer, and Novartis. FLC received consulting fees from Takeda, Amgen, Novartis, AstraZeneca, and Roche; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Takeda, Amgen, Novartis, AstraZeneca, and Roche; and received support for attending meetings or travel from Takeda and Amgen. CG received consulting fees from Karyopharm, Menarini, and Roche; received payment or honoraria for lectures, presentations, speakers' bureaux, manuscript writing, or educational events from MSD, BMS, Novartis, Amgen, Sanofi, Eli Lilly, GSK, Roche, Takeda, Boehringer, AstraZeneca, and Pfizer; and participated on a Data Safety Monitoring Board or Advisory Board for MSD, BMS, Novartis, Amgen, Sanofi, Eli Lilly, GSK, Roche, Takeda, Boehringer Ingelheim, AstraZeneca, and Pfizer. FP received partial funding to institution and experimental study drug from Pfizer; received financial support to institution from Roche, Bayer, AstraZeneca, Pfizer, Incyte, Tesaro/GSK, and Merck; and received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Bayer, Pierre Fabre, AstraZeneca, Incyte, Ipsen, Clovis, Astellas, Sanofi, Roche, and Pfizer. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Mesothelioma comprises a group of rare cancers arising from the mesothelium of the pleura, peritoneum, tunica vaginalis testis and pericardium. Mesothelioma is generally associated with asbestos exposure and has a dismal prognosis, with few therapeutic options. Several next generation sequencing (NGS) experiments have been performed on mesothelioma arising at different sites. These studies highlight a genomic landscape mainly characterized by a high prevalence (>20%) of genomic aberrations leading to functional losses in oncosuppressor genes such as BAP1, CDKN2A, NF2, SETD2 and TP53. Nevertheless, to date, evidence of the effect of targeting these alterations with specific drugs is lacking. Conversely, 1-2% of mesothelioma might harbor activating mutations in oncogenes with specifically approved drugs. The goal of this review is to summarize NGS applications in mesothelioma and to provide insights into target therapy of mesothelioma guided by NGS.

Introduction: Pseudomyxoma peritonei (PMP) is a rare, slow growing tumor, traditionally considered chemoresistant. The only curative approach is cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). At disease relapse, or in patients with inoperable disease at diagnosis, no standard treatment has been defined, though nonrandomized series showed promising results with fluoropyrimidine-based regimens., Patients and Methods: We conducted a prospective study in patients with relapsed or unresectable PMP and confirmed disease progression at baseline. Patients received MMC (7 mg/m 2 every 6 weeks, up to a maximum of 4 cycles) plus metronomic capecitabine (625 mg/sqm/day b.i.d.) and bevacizumab (7.5 mg/kg every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), overall response rate according to RECIST v1.1 criteria, serum markers response and safety., Results: Fifteen patients were included. At a median follow-up of 26.1 months (IQR, 17.7-49.6), median PFS was 17.9 months (95% CI, 11.0-NE), with 1-year PFS and OS rates of 73% and 87%. Safety profile was manageable, with only 13% G3/G4 treatment-related adverse events., Conclusion: Metronomic capecitabine, bevacizumab, and MMC are an active regimen in advanced and progressive PMP and favorably compares with historical series., Competing Interests: Disclosure F.P. received honoraria from Amgen, Bayer, Servier, Merck-Serono, MSD, BMS, Takeda, Astellas, Pierre-Fabre and received research grants for academic studies from Bristol-Myers Squibb, AstraZeneca, Agenus, Incyte, Amgen., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Pleural mesothelioma (PM) is a rare and aggressive cancer. PICC devices are widely used in cancer patients. The aim of the study is to evaluate the quality of life of patients with PICC diagnosed with PM treated at the Hospital of Casale Monferrato and Alessandria (Italy), an area with a high incidence of asbestos-related diseases., Study Design and Methods: Longitudinal prospective observational study with data collection at PICC insertion (T0), after 3 months (T1), 6 months (T2), and 9 months (T3). Participants were aged >18 years, diagnosed with PM, eligible for PICC insertion. Questionnaires used: EORTC QLQ-C30, EORTC QLQ-LC13, and HADS rating scale., Results: Twenty-eight patients were enrolled. The mean age was 68.93 years (SD 9.13), mostly male (57.1%). The most frequent cancer stage at diagnosis was III (39.3%), then I (32.1%), and IV (21.4%). 85.7% were treated with chemotherapy, 14.3% also with immunotherapy. 96.4% of patients reported no complications during PICC implantation. The perception of health status and quality of life, measured on a scale of 1-7, was in line with an average score of 5 during the evaluation period. The total anxiety and depression score remained normal for most patients (0-7)., Conclusions: The PICC management involved a multidisciplinary team with different skills: study findings revealed the key role that dedicated nurses play in PICC placement and ensuring patient problems are promptly addressed. From our study results, PICC placement does not seem to negatively impact the patient's quality of life., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SD reports travel and accommodation expenses and speaker engagements from Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, and Pierre Fabre, not associated with this publication.

Background: Although SARS-CoV-2 vaccines immunogenicity in patients with cancer has been investigated, whether they can significantly improve the severity of COVID-19 in this specific population is undefined., Methods: Capitalizing on OnCovid (NCT04393974) registry data we reported COVID-19 mortality and proxies of COVID-19 morbidity, including post-COVID-19 outcomes, according to the vaccination status of the included patients., Results: 2090 eligible patients diagnosed with COVID-19 between 02/2020 and 11/2021 were included, of whom 1930 (92.3%) unvaccinated, 91 (4.4%) fully vaccinated and 69 (3.3%) partially vaccinated. With the exception of a higher prevalence of patients from the UK (p = 0.0003) and receiving systemic anticancer therapy at COVID-19 diagnosis (p = 0.0082) among fully vaccinated patients, no demographics/oncological features were associated with vaccination status. The 14-days case fatality rate (CFR) (5.5% vs 20.7%, p = 0.0004) and the 28-days CFR (13.2% vs 27.4%, p = 0.0028) demonstrated a significant improvement for fully vaccinated patients in comparison with unvaccinated patients. The receipt of prior full vaccination was also associated with reduced symptomatic COVID-19 (79.1% vs 88.5%, p = 0.0070), need of COVID-19 oriented therapy (34.9% vs 63.2%, p < 0.0001), complications from COVID-19 (28.6% vs 39.4%, p = 0.0379), hospitalizations due to COVID-19 (42.2% vs 52.5%, p = 0.0007) and oxygen therapy requirement (35.7% vs 52%, p = 0.0036). Following Inverse Probability Treatment Weighting (IPTW) procedure no statistically significant difference according to the vaccination status was confirmed; however, all COVID-19 related outcomes were concordantly in favour of full vaccination. Among the 1228 (58.8%) patients who underwent a formal reassessment at participating centres after COVID-19 resolution, fully vaccinated patients experienced less sequelae than unvaccinated patients (6.7% vs 17.2%, p = 0.0320)., Conclusions: This analysis provides initial evidence in support of the beneficial effect of SARS-CoV-2 vaccines against morbidity and mortality from COVID-19 in patients with cancer., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: As corresponding author of the abovementioned manuscript, I declare on behalf of my co-authors the following conflict of interests: David J Pinato received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, EISAI, Falk Foundation, travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, DaVolterra and Astra Zeneca; research funding (to institution) from MSD and BMS.Aleix Prat has declared personal honoraria from Pfizer, Roche, MSD Oncology, Eli Lilly, and Daiichi Sankyo; travel, accommodations, and expenses paid by Daiichi Sankyo; research funding from Roche and Novartis; and consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb.Matteo Lambertini acted as consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, Seagen and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen and Sandoz outside the submitted work.Joan Brunet has declared consulting/advisory role for MSD and Astra Zeneca.Alessandra Gennari has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds: EISAI, Eli Lilly, and Roche. CMV has received travel grants and other honoraria from BMS, MSD, Novartis and Roche.Gianluca Gaidano has declared consulting/advisory role for Janssen, Abbvie, Astra-Zeneca and BeiGene, and speaker fees from Janssen and Abbvie.Lorenza Rimassa received consulting fees from Taiho Oncology, Servier, Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi; travel expenses from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks.Joseph Tabernero reported consulting fees from Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Scandion Oncology, Servier, Sotio Biotech, Taiho, Tessa Therapeutics and TheraMyc. He also reported speaker's fees from Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER). He also declared institutional research support from Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen-Cilag SA, MedImmune, Menarini, Merck Health KGAA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc, Spanish Association Against Cancer Scientific Foundation and Cancer Research UK.Alessio Cortellini received consulting fees from MSD, BMS, AstraZeneca, Roche; speakers' fee from AstraZeneca, MSD, Novartis and Eisai.All remaining authors have declared no conflicts of interest.London, April 18th, 2022., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pleural mesothelioma (PM) is an aggressive tumor with few therapeutic options. Although patients with epithelioid PM (ePM) survive longer than non-epithelioid PM (non-ePM), heterogeneity of tumor response in ePM is observed. The role of the tumor immune microenvironment (TIME) in the development and progression of PM is currently considered a promising biomarker. A few studies have used high-throughput technologies correlated with TIME evaluation and morphologic and clinical data. This study aimed to identify different morphological, immunohistochemical, and transcriptional profiles that could potentially predict the outcome. A retrospective multicenter cohort of 129 chemonaive PM patients was recruited. Tissue slides were reviewed by dedicated pathologists for histotype classification and immunophenotype of tumor-infiltrating lymphocytes (TILs) and lymphoid aggregates or tertiary lymphoid structures (TLS). ePM (n = 99) survivors were further classified into long (>36 months) or short (<12 months) survivors. RNAseq was performed on a subset of 69 samples. Distinct transcriptional profiling in long and short ePM survivors was found. An inflammatory background with a higher number of B lymphocytes and a prevalence of TLS formations were detected in long compared to short ePM survivors. These results suggest that B cell infiltration could be important in modulating disease aggressiveness, opening a pathway for novel immunotherapeutic approaches.

A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker for diagnosis of pleural mesothelioma (PM) and the most used for monitoring treatment. Radiological assessment of PM, based on modified RECIST (mRECIST) criteria, is challenging. This pilot study was designed to evaluate whether SMRP levels correlated over time with mRECIST score. Serial serum samples from PM patients were collected and SMRP levels were measured and compared with the mRECIST score obtained through centralized CT scans by blinded review. The within-patient SMRP-mRECIST relationship over time was estimated through a normal random-effects regression approach applied to the log-transformed mRECIST score. Overall, 58 PM patients were included (46 males and 12 females) with a median age at diagnosis of 67 years (min-max = 48-79), 44 (76%) with epithelioid and 14 (24%) with non-epithelioid histology. The total number of SMRP measurements and CT scans considered for analysis was 183. There was a statistically significant correlation between SMRP and mRECIST score in the 2 cohorts considered both separately and jointly. These results, although exploratory, suggest that SMRP measurement might be considered as an adjunct to monitor PM patients in order to delay CT scans time interval, thus warranting further investigation.

Pancreatoduodenectomy is one of the most challenging surgical specimens for pathologists. Recently, two different, standardized protocols have been proposed: the axial slicing Leeds protocol (LP) and the bi-valving Adsay protocol (AP). Comparison between standardized and non-standardized protocols (NSP) was performed with emphasis on margin involvement and lymph node yield. Pancreatoduodenectomy cases were retrospectively recruited: 46 sampled with LP, 52 cases with AP and 46 cases with NSP. Clinico-pathologic data and rates of margin/surface involvement were collected and their prognostic influence on survival was assessed. Statistical differences between NSP and AP and LP were seen for nodal yield (p = 0.0001), N+ (p = 0.0001) and lymph node ratio - LNR (p < 0.0008) but not between AP and LP. Differences in R1/R0 status were statistically significant between NSP group (R1-15%) and both the LP (R1-73.9%) and AP (R1-70%) groups (p = 0.0001) but not between LP and AP groups. At univariate survival analysis, grade (p = 0.0023) and number of involved margins (p = 0.0096) in AP and "N-category" (p = 0.0057) "resection margin status" (p = 0.0094), "stage" (p = 0.0143), and "number of involved margins" (p = 0.00398) in LP were statistically significant, while no variable was significant in the NSP group. At multivariate analysis "N category," "resection margin status," "stage," "number of involved margins," and "LNR" retained significance for the LP group. These results show that both LP and AP perform better than non-standardized sampling making standardization mandatory in pancreatoduodenectomy cut up. Both AP and LP show strengths and weaknesses, and these may impact on the choice of protocol in different institutions.

Background: Malnutrition is common in cancer patients, particularly in those affected by gastrointestinal malignancies, and negatively affects treatment tolerance, survival, functional status, and quality of life (QoL). Nutritional support, including supplemental parenteral nutrition (SPN), has been recommended at the earliest opportunity in malnourished cancer patients. The limited available evidence on the efficacy of SPN in gastrointestinal cancer patients is positive, particularly with regards to QoL, body composition, and energy intake, but the evidence on survival is still scanty. Furthermore, studies regarding the early administration of SPN in combination with nutritional counseling from the beginning of first-line chemotherapy (CT) are lacking. We hypothesize that early systematic SPN in combination with nutritional counseling (NC), compared with NC alone, can benefit patients with previously untreated metastatic gastric cancer at nutritional risk undergoing first-line CT., Methods: The aim of this pragmatic, multicenter, randomized (1:1), parallel-group, open-label, controlled clinical trial is to evaluate the efficacy in terms of survival, weight maintenance, body composition, QoL and feasibility of cancer therapy of early systematic SNP. This is in combination with NC, compared with NC alone, in treatment-naïve metastatic gastric cancer patients at nutritional risk undergoing first-line CT., Discussion: Malnutrition in oncology remains an overlooked problem. Although the importance of SPN in gastrointestinal cancer patients has been acknowledged, no studies have yet evaluated the efficacy of early SPN in metastatic gastric patients undergoing CT. The present study, which guarantees the early provision of nutritional assessment and support to all the enrolled patients in accordance with the recent guidelines and recommendations, could represent one of the first proofs of the clinical effectiveness of early intensive nutritional support in cancer patients undergoing CT. This study could stimulate further large randomized trials in different cancer types, potentially resulting in the improvement of supportive care quality., Trial Registration: This study is registered on ClinicalTrials.gov: NCT03949907., Competing Interests: Conflict of interest statement: RC has received research funding from Baxter Healthcare Corporation. RC and PP have served as consultants and/or on advisory panels for Baxter Healthcare Corporation. LB has served as scientific lecturer and/or on advisory panels for Baxter Healthcare Corporation, Roche, Merck, Teva, Genzyme and Novartis. RC and PP have participated in speakers’ bureaus for Baxter Healthcare Corporation. RC and EC have participated in speakers’ bureaus for Akern s.r.l., (© The Author(s), 2020.)