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Background: Inclusion of patient-reported outcomes (PROs) in oncology clinical trials is strongly recommended. However, selecting the most appropriate patient-reported outcome measures (PROMs) is not easy. This study aimed to develop a breast cancer (BC) specific comprehensive archive of PROMs., Methods: As part of the PRO4All project, we identified available PROMs in oncology by searching facit.org, eortc.org, eprovide.mapi-trust.org, PubMed, ema.europa.eu (European Public Assessment Reports) and published reviews. For this analysis, only BC tools were extracted. We described information about PROM name, type of questionnaire, questionnaire variant(s), recall period, number of items, and presence of minimum clinically important difference (MCID) reference in literature. Then, we assigned each item to a specific domain according to a predefined taxonomy of 38 items for outcome classification., Results: We identified and analyzed 383 PROMs. Of these, 29 were BC specific, but 2 were excluded because the questionnaires description was not available. 6 (22.2 %) were variants of another questionnaire. All questionnaires were self-reported. In 6 cases (22.2 %) the recall period to consider was the "last week". The mean number of items per questionnaire was 25.81 (range 6-71). 602 items were assigned to an outcome domain: emotional functioning/wellbeing in 26.6 % of cases, physical functioning in 14.1 %, delivery of care in 10.8 %, and general outcomes in 10.5 %. MCID reference was found only in 4 (14.8 %) cases., Conclusions: The newly developed archive represents a useful tool to optimize the use of PROMs in the evaluation of treatments in BC patients, promoting a patient-centered approach both in clinical research and practice., Competing Interests: Declaration of competing interest F.G. reports honoraria from Eli Lilly, MSD, AstraZeneca, Novartis, Pfizer, Roche, Tesaro/GlaxoSmithKline. A.S. reports honoraria from Eli Lilly, MSD, AstraZeneca and Janssen; Travel support from Bristol-Myers Squibb, Roche and AstraZeneca; funding for research from AIRC. C.P. reports honoraria from Amgen, Astellas, AstraZeneca, Bayer, Bristol Meyer Squibb, Celgene, Clovis Oncology, Eisai, Ipsen, Janssen, Incyte, Merck-Serono, Merck Sharp and Dohme, Novartis, Roche, Sandoz, Sanofi, and Servier for consultancy or participation to advisory boards. M.D.M. reports honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, Takeda for consultancy or participation to advisory boards; direct research funding from Tesaro/GlaxoSmithKline, institutional funding for work in clinical trials/contracted research from Beigene, Exelixis, MSD, Pfizer and Roche. A.A.V.; C.B.; F.M.; M.M.; O.C. have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Prostate cancer (PC) is generally a hormone-dependent tumor. Androgen deprivation therapy ( has been the standard of care in metastatic disease for more than 80 years. Subsequent studies have highlighted the efficacy of ADT even in earlier disease settings such as in localized disease or in the case of biochemical recurrence (BCR). Improved knowledge of PC biology and ADT resistance mechanisms have led to the development of novel generation androgen receptor pathway inhibitors (ARPI). Initially used only in patients who became resistant to ADT, ARPI have subsequently shown to be effective when used in patients with metastatic hormone-naive disease and in recent years their effectiveness has also been evaluated in localized disease and in case of BCR. The objective of this review is to describe the current role of agents interfering with the androgen receptor in different stages of PC and to point out future perspectives., Competing Interests: Disclosure Fabio Turco: Travel support: Bayer. Silke Gillessen: (last 3 years) personal honoraria for participation in advisory boards from Amgen, MSD; other honoraria from Radio-televisione Svizzera Italiana (RSI), German-speaking European School of Oncology (DESO); invited speaker for ESMO, Swiss group for Clinical Cancer Research (SAKK), Swiss Academy of Multidisciplinary oncology (SAMO), Orikata academy research group, China Anticancer Association Genitourinary Oncology Committee (CACA-GU); Speaker's bureau for Janssen Cilag; travel grant from ProteoMEdiX and AstraZeneca. Institutional honoraria for participation in advisory boards or in Independent Data Monitoring Committees and Steering Committees from AAA International, Amgen, AstraZeneca, Astellas Pharma, Bayer, Bristol-Myers Squibb, DAIICHI Sankyo, Janssen, Modra Pharmaceuticals, MSD, Myriad Genetic, Novartis, Orion, Pfizer, Roche, Telixpharma, Tolermo Pharmaceutcials; invited speaker for Swiss group for Clinical Cancer Research (SAKK), Cold Spring Harbor Laboratory, ASCO GU; other honoraria from PeerVoice, Silvio Grasso Consulting, WebMD-Medscape. Patent royalties and other intellectual property for a research method for biomarker WO2009138392 Ursula Vogl: Advisory role (institutional): Janssen, Astellas, Merck, MSD, Pfizer, Roche, Bayer, BMS, Novartis AAA. Travel support: Janssen, Merck, Ipsen; Speakers Bureau (compensated, institutional): Janssen, Astellas, Pfizer, Roche, SAMO, BMS, Ipsen. Grant: Fond'Action The remaining authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Despite the interest from the scientific community and regulatory agencies, limited data are available on the association between health-related quality-of-life (QoL) results, outcome of efficacy and drug approvals., Materials and Methods: We updated the previously published meta-research study of phase III clinical trials in patients with solid tumours treated with systemic treatments, published from 2012 to 2021 in 11 selected journals. For the present analysis, we focused on studies conducted in the advanced setting. The primary outcome was the association of global QoL results with study primary endpoints (EP1), overall survival (OS) and progression-free survival (PFS), while a secondary outcome was the frequency of positive global QoL results among treatments approved by regulatory agencies [European Medicines Agency (EMA)/Food and Drug Administration (FDA)]. A descriptive analysis was carried out and the association between QoL results and characteristics of studies and of publications was tested., Results: Five hundred and ninety-two eligible publications were identified from 2012 to 2021. The primary endpoint was OS in 298 clinical trials (50.3%) and PFS in 304 clinical trials (51.4%). A positive result in EP1 analysis was reported in 124 trials (41.6%) with OS as EP1 and in 182 trials (59.5%) with PFS as EP1. Among studies with positive OS and PFS, global QoL results were positive in 39 (31.5%) and 45 studies (24.7%), respectively. FDA and EMA approvals were available for 143 (24.2%) and 142 studies (24%), respectively. Among these, global QoL results were positive in 55 (38.5%) and 56 studies (39.4%), respectively. QoL results were available for most drugs approved by regulatory agencies, but the proportion of approvals with positive global QoL results was not significantly increased from 2012-2016 to 2017-2021., Conclusions: Despite QoL data being available for most cancer treatments recently approved by regulatory agencies, QoL improvement has been demonstrated in a minority of studies with positive results in the primary endpoint., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Prostate cancer (PCa) treatments are associated with a detrimental impact on bone health (BH) and body composition. However, the evidence on these issues is limited and contradictory. This consensus, based on the Delphi method, provides further guidance on BH management in PCa., Materials and Methods: In May 2023, a survey made up of 37 questions and 74 statements was developed by a group of oncologists and endocrinologists with expertise in PCa and BH. In June 2023, 67 selected Italian experts, belonging to the Italian scientific societies Italian Association of Medical Oncology and Italian Network for Research in Urologic-Oncology (Meet-URO), were invited by e-mail to complete it, rating their strength of agreement with each statement on a 5-point scale. An agreement ≥75% defined the statement as accepted., Results: In non-metastatic hormone-sensitive PCa, the panel agreed that androgen deprivation therapy (ADT) alone implies sufficient fracture risk to warrant antifracture therapy with bone-targeting agents (BTAs) for cancer treatment-induced bone loss (CTIBL) prevention (79%). Therefore, no consensus was reached (48%) for the treatment with BTAs of patients receiving short-term ADT (<6 months). All patients receiving active treatment for metastatic hormone-sensitive PCa (75%), non-metastatic castration-resistant PCa (89%) and metastatic castration-resistant PCa (mCRPC) without bone metastases (84%) should be treated with BTAs at the doses and schedule for CTIBL prevention. All mCRPC patients with bone metastasis should be treated with BTAs to reduce skeletal-related events (94%). In all settings, the panel analyzed the type and timing of treatments and examinations to carry out for BH monitoring. The panel agreed on the higher risk of sarcopenic obesity of these patients and its correlation with bone fragility., Conclusions: This consensus highlights areas lacking major agreement, like non-metastatic hormone-sensitive prostate cancer patients undergoing short-term ADT. Evaluation of these issues in prospective clinical trials and identification of early biomarkers of bone loss are particularly urgent., Competing Interests: Disclosure DS reports fee from advisory boards by AstraZeneca, Lilly, Daiiki-Sanchio, Astellas, Janssenn, Recordati, Gilead, Pfizer, MSD, Novartis, BMS, Roche, EISAI and Ipsen. MDM reports honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, GlaxoSmithKline, Amgen, Merck, Takeda for consultancy or participation to advisory boards; direct research funding from Tesaro/GlaxoSmithKline; institutional funding for work in clinical trials/contracted research from Beigene, Exelixis, MSD, Pfizer and Roche. UDG: consulting or advisory role for Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, DompéFarmaceutici, Eisai, Ipsen, Janssen, Merck KgaA, MSD, Novartis and Pfizer; research funding (institution) from AstraZeneca, Roche and Sanofi; and travel accommodations from AstraZeneca, Ipsen and Pfizer. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Immunotherapy with immune checkpoint inhibitors (ICI) is increasingly employed in oncology. National and international endocrine and oncologic scientific societies have provided guidelines for the management of endocrine immune-related adverse events. However, guidelines recommendations differ according to the specific filed, particularly pertaining to recommendations for the timing of endocrine testing. In this position paper, a panel of experts of the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) offers a critical multidisciplinary consensus for a clear, simple, useful, and easily applicable endocrine-metabolic assessment checklist for cancer patients on immunotherapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: V.R. has received a travel grant from Androlabs. M.G. has received honoraria for speaker fees and/or travel grants for scientific meetings from AAA, AstraZeneca, Boehringer-Ingelheim, Bruno Farm., Eli-Lilly, IBSA, Lifescan, Mundipharma, Novo Nordisk and Sanofi, and served on scientific advisory panels for Boehringer-Ingelheim, Merck Sharp & Dohme and Novo Nordisk. S.F. serves on the scientific advisory board of, has a consulting relationship with and reports receiving support for travel expenses from Novartis, Teva, Roche, BMS, Lilly and Ipsen. R.D. serves on the scientific advisory board and has a consulting relationship with Ipsen, Novartis, Pfizer, Sanofi Genzyme, AstraZeneca, Janssen, Gilead, Lilly, Gilead, EUSA Pharma; and reports support for travel, accommodation and expenses from Ipsen and Sanofi Genzyme. F.G. has served as an advisor for AstraZeneca, Eli Lilly and Novo Nordisk; has served as a research investigator for Eli Lilly and Roche Diabetes Care; has served as a speaker for AstraZeneca and Eli Lilly; has served as a consultant for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Roche Diabetes Care and Sanofi; and has received grants from Eli Lilly, Lifescan and Roche Diabetes Care. N.S. received fees for consulting from Roche, Lilly, Servier. All other authors declare no conflict of interest. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Advances in surgical techniques and systemic treatments have increased the likelihood of achieving radical surgery and long-term survival in metastatic colorectal cancer (mCRC) patients with initially unresectable colorectal liver metastases (CRLMs). Nonetheless, roughly half of the patients resected after an upfront systemic therapy experience disease relapse within 6 months from surgery, thus leading to the question whether surgery is actually beneficial for these patients., Materials and Methods: A real-world dataset of mCRC patients with initially unresectable liver-limited disease treated with conversion chemotherapy followed by radical resection of CRLMs at three high-volume Italian institutions was retrospectively assessed with the aim of investigating the association of baseline and pre-surgical clinical, radiological and molecular factors with the risk of relapse within 6 or 12 months from surgery., Results: Overall, 268 patients were included in the analysis and 207 (77%) experienced recurrence. Ninety-six (46%) of them had disease relapse within 6 months after CRLM resection and in spite of several variables associated with early recurrence at univariate analyses, only primary tumour resection at diagnosis [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.89, P = 0.02] remained significant in the multivariable model. Among patients with resected primary tumours, pN+ stage was associated with higher risk of disease relapse within 6 months (OR 3.02, 95% CI 1.23-7.41, P = 0.02). One hundred and forty-nine patients (72%) had disease relapse within 12 months after CRLMs resection but none of the analysed variables was independently associated with outcome., Conclusions: Clinical, radiological and molecular factors assessed before and after conversion chemotherapy do not reliably predict early recurrence after secondary resection of initially unresectable CRLMs. While novel markers are needed to optimize the cost/efficacy balance of surgical procedures, CRLM resection should be offered as soon as metastases become resectable during first-line chemotherapy to all patients eligible for surgery., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Oncologists tend to under-report subjective symptoms during cancer treatment. This study describes the under-reporting rate of selected symptoms and explores its association with overall survival (OS). A secondary aim is to test the association of patient-reported symptoms with OS., Patients and Methods: This is a post hoc analysis on data pooled from 12 randomized trials, promoted by the National Cancer Institute of Naples (Italy), enrolling patients between 2002 and 2019, with published primary analyses. Occurrence and grade of six side-effects (anorexia, nausea, vomiting, constipation, diarrhea and fatigue) reported by physicians were compared with corresponding symptoms reported by patients in quality-of-life (QoL) questionnaires. Under-reporting was defined as the rate of cases reported grade 0 by the physician while grade ≥1 by the patient. Prognostic value was tested in a multivariable model stratified by trial, including age, sex and performance status as confounders. A landmark threshold was defined for OS analyses., Results: 3792 patients with advanced lung, ovarian, pancreatic, breast or colorectal cancer were pooled; 2603 (68.6%) were eligible having at least one toxicity assessment and one QoL questionnaire, before the first planned disease restaging. Concordance between physicians' and patients' reporting was low with Cohen's k coefficients ranging from 0.03 (fatigue) to 0.33 (vomiting). Under-reporting ranged from 52.7% (nausea) to 80.5% (anorexia), and was not associated with OS. Patient-reported anorexia, vomiting and fatigue ('a little' or more) were significantly associated with shorter OS., Conclusions: Under-reporting of treatment side-effects is frequent, but it does not affect OS. Patients' reported symptoms should be used for prognostic evaluation., Competing Interests: Disclosure LA: honoraria from Pfizer, EliLilly. RDL: honoraria from Astellas, Pfizer, Janssen. PDP: Honoraria from Lilly, Gilead, MSD, Roche, Exact Sciences, Novartis; support for attending meetings from Gilead, Lilly, Istituto Gentili, MSD. CG: honoraria as speaker bureau or advisory board member or consultant from MSD, BMS, AstraZeneca, Roche, Eli Lilly, Pfizer, Amgen, Novartis, GSK, Takeda, Boehringer, Menarini, Karyopharm, Sanofi. AM: honoraria for speaker’s bureau or advisory board from Roche, AstraZeneca, BMS, Pfizer, MSD, Boehringer, Takeda, Novartis, Lilly, Sanofi. SP: honoraria from AstraZeneca, MSD, Roche, GSK, Pharmamar; research funding from Roche, AstraZeneca, MSD, Pfizer, GSK. FN: honoraria from Seagen. AA: honoraria from Amgen, MSD, Eisai, Bristol-Meyers; consulting or advisory role: Amgen, AstraZeneca, MSD, Eisai, Bayer. AG: honoraria from Janssen. MDM: honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, Takeda, Amgen, Merck for consultancy or participation to advisory boards; direct research funding from Tesaro/GlaxoSmithKline; institutional funding for work in clinical trials/contracted research from Beigene, Exelixis, MSD, Pfizer and Roche. FP: institutional support or grants for clinical trials from Roche, Bayer, AstraZeneca, Pfizer, Incyte, Tesaro/GSK, Merck; honoraria for participation on advisory boards from Bayer, Pierre Fabre, AstraZeneca, Incyte, Ipsen, Clovis, Astellas, Sanofi, Roche, Pfizer. MCP: institutional funding for clinical research from Roche, AstraZeneca, Bayer; honoraria for educational activities from Astellas, Pfizer, Ipsen, AstraZeneca; support for attending meetings from Menarini. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Dual immune checkpoint blockers regimen represents a standard first-line therapy in unresectable pleural mesothelioma (PM). Novel combination strategies, including immune checkpoint blockers and antiangiogenic drugs, are currently under investigation in this setting. We aimed to assess the efficacy of the chemoimmunotherapy combination by reference to literature evidence., Methods: A systematic review and meta-analysis of trials with first-line platinum-based chemotherapy associated with programmed death-ligand 1 and programmed cell death protein 1 agent in unresectable PM. We estimated the weighted summary proportion of disease response, along with the landmark probability of survival outcomes., Results: A total of 349 patients with unresectable PM from four trials (DREAM, PrE0505, JME-001, and IND.227) were included, 79% (n = 274) with epithelioid and 21% (n = 75) with nonepithelioid histologic type. In aggregate, the objective response rate was 59.2% (95% confidence interval [CI]: 50.3%-67.9%) and disease control rate was 92.2% (95% CI: 89.2%-94.8%). Comparing epithelioid versus nonepithelioid tumors, the objective response rate was 64.5% versus 46.4%, (p < 0.001) and the disease control rate was 92.3% versus 80.0%, (p = 0.043), with an OR of 2.56 (95% CI: 1.51-4.32) for disease response and of 3.37 (95% CI: 0.99-11.47) for disease control. The aggregated estimated probability of progression-free survival was 63% (95% CI: 53%-71%) at 6 months and 25% (95% CI: 21%-31%) at 12 months, whereas the 6-, 12- and 24-month overall survival rates were 88% (95% CI: 81%-93%), 71% (95% CI: 61%-79%) and 39% (95% CI: 34%-45%), respectively., Conclusions: According to our analysis, first-line chemoimmunotherapy holds promise as a new treatment approach for PM, exhibiting encouraging survival outcomes and an enhanced response rate, including for the epithelioid subtype. Ongoing studies are necessary to establish its precise placement within the treatment algorithm., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Treatment for HER2-positive (+) metastatic breast cancer has improved in the last decade. We analyzed treatment changes over time and their impact on patients outcomes in a real-world dataset., Methods: Data from 637 HER2+ patients with metastatic breast cancer enrolled in the multicenter Italian GIM14/BIOMETA study were retrieved. Progression-free survival (PFS) over time was evaluated according to the type of anti-HER2 therapy, disease onset (de novo vs. relapsing), metastatic site, and year of treatment (2000-2013 vs. 2014-2020)., Results: Median follow-up was 64.4 months. Overall, for first-line therapies, mPFS was 16.5 vs 19.5 months for patients treated in 2000-2013 vs 2014-2020 (HR: 0.78, 95% CI:0.65-0.94, P = 0.008). mPFS improved over time in all patients except for those with brain metastasis. Interestingly mPFS was 17.4 vs13.4 months (HR, 1.49; 95% CI, 1.13-1.98, P = 0.005) in 2000-2013 and 24.4 vs 20.9 months (HR 1.04; 95% CI 0.78-1.40 p = 0.77) in 2014-2020 in pts without vs with liver metastases. For second line therapies, the overall median PFS was 9.6 months (95% CI, 8.31-10.97) and did not change over time., Conclusion: Median first-line PFS improved since 2014, mainly due to the introduction of pertuzumab. The outcome of patients with liver metastases appears to have improved in recent years. Patients with brain metastases had the worst PFS, which also did not improve over time., Competing Interests: Declaration of competing interest G.A. reports support for the present manuscript from Astra Zeneca and Istitutional Grant from Astra Zeneca; consulting fees from Astra Zeneca, Daiichi-Sankyo, Novartis, Roche, Pfizer, Eli Lilly, Gilead, Seagen; personal fees for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra Zeneca, Daichii Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Novartis, Roche, Seagen, Viatris; support for attending meetings and/or travel from Daichii - Sankyo, Roche, Novartis; participation on a Data Safety Monitoring Board or Advisory Board for Astra Zeneca, Daichii - Sankyo, Eisai, Eli Lilly, Gilead, Novartis, Roche, Seagen. C.B. reports personal fees for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Eli Lilly, Novartis, Pfizer; personal fees for support for attending meetings and/or travel from Roche, Novartis; personal fees for participation on a Data Safety Monitoring Board or Advisory Board from Roche, Novartis. C.D.A. reports personal fees from AstraZeneca, Lilly, GSK, Novartis, Seagen, and Pfizer, Advisory Board for Roche, AstraZeneca, Lilly, GSK, Novartis, Seagen, and Pfizer, support for attending meetings and/or travel AstraZeneca, Lilly, GSK, Novartis, Celgene, and Pfizer, grants (to the Institution) from Novartis. M.D.L. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Eli Lilly, Menarini; support for attending meetings and/or travel from Gilead, Roche, Astra Zeneca, Novartis, Roche, Pfizer, Gilead, Seagen, Daiichi-Sankyo, Pfizer, Eli Lilly, Genetic, Pierre Fabre, GSK, Exact Sciences, Tomalab, Eisai, MSD and participation on a Data Safety Monitoring Board or Advisory Board for Seagen, Eli Lilly, Novartis, Pierre Fabre, Sanofi Genzyme, GSK, Gilead, Astra-Zeneca, Daiichi-Sankyo, MSD; Roche, Eisai, Exact Scences. L.D.M. reports grants to the Institution for patient enrollment in studies from Eli Lilly, Novartis, Roche, Daiichi - Sankyo, Seagen; consulting fees from Ely Lilli, Roche, Novartis, Pfizer, Astra Zeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact sciences, Ipsen, Agendia, GSK, Daiichi – Sankyo; support for attending meetings and/or travel from Roche, Pfizer, Eisai, Daiichi - Sankyo; participation on a Data Safety Monitoring Board or Advisory Board for Novartis, Roche, Eli Lilly, Pfizer, Daiichi - Sankyo, Exact sciences, Gilead, Pierre Fabre, Eisai, Astra Zeneca, Agendia, GSK. M.D.M reports personal fees for Advisory boards or consultant role: Astra Zeneca, Novartis, Roche, Pfizer, Eisai, MSD, Janssen, Boehringer Ingelheim, Takeda, Amgen, Merck, Servier and research grant to the Institution: Tesaro, GlaxoSmithKline. A.F. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Astra Zeneca, Eli Lilly, Pfizer, Novartis, Gilead; support for attending meetings and/or travel for Astra Zeneca, Roche, Gilead, Eli Lilly; participation on a Data Safety Monitoring Board or Advisory Board for Roche, Novartis, Lilly, Pfizer, MSD, Dompè, Pierre Fabre, Eisai, Sophos, Epionpharma, Gilead, Seagen, Astra Zeneca, Exact Science. M.G. reports consulting fees from Lilly, Celgene, Novartis, Pfizer, Astra Zeneca, Daiichi-Sankyo, MSD, Gilead, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events for Lilly, Celgene, Novartis, Pfizer, Istituto Gentili, Eisai Europe Ltd, Roche Astra Zeneca, Daiichi - Sankyo, MSD, Gilead, support for attending meetings and/or travel from Novartis, Pfizer, Roche. L.M. reports personal fees from MSD for lectures, presentations, speakers’ bureaus, manuscript writing or educational events and support for attending meetings and/or travel from Janssen. F.P. reports consulting fees from Astra Zeneca, Daichii - Sankyo, Novartis, Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra Zeneca, Daichii – Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Novartis, Roche, Seagen, Viatris; support for attending meetings and/or travel from Daichii - Sankyo, Roche; participation on a Data Safety Monitoring Board or Advisory Board for Astrazeneca, Daichii – Sankyo, Eisai, Eli Lilly, Gilead, Novartis, Roche, Seagen, Viatris. F.R reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, Astra Zeneca, Lilly, Pfizer, Novartis, Gilead; support for attending meetings and/or travel from Astra Zeneca, Roche, Gilead, Lilly; participation on a Data Safety Monitoring Board or Advisory Board for Roche, Novartis, Eli Lilly, Pfizer, MSD, Dompè, Pierre Fabre, Eisai, Sophos, Epionpharma, Gilead, Seagen, Astra Zeneca, Exact Science. F.S. reports honoraria for presentations and educational materials from Novartis. Authors not mentioned declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Patient Reported Outcome for Fighting FInancial Toxicity (PROFFIT) questionnaire was developed to measure financial toxicity (FT) and identify its determinants. The aim of the present study was to confirm its validity in a prospective cohort of patients receiving anticancer treatment., Patients and Methods: From March 2021 to July 2022, 221 patients were enrolled at 10 Italian centres. Selected items of the EORTC-QLQ-C30 questionnaire represented the anchors, specifically, question 28 (Q-28) on financial difficulties, and questions 29-30 measuring global health status/quality of life (HR-QOL). The study had 80% power to detect a 0.20 correlation coefficient (r) between anchors and PROFFIT-score (items 1-7, range 0-100, 100 indicating maximum FT) with bilateral alpha 0.05 and 80% power. Confirmatory factor analysis was conducted. FT determinants (items 8-16) were described., Results: Median age of patients was 65 years, 116 (52.5%) were females, 96 (43.4%) had low education level. Confirmatory factor analysis confirmed goodness of fit of the PROFFIT-score. Significant partial correlation of PROFFIT-score was found with Q-28 (r = 0.51) and HR-QOL (r = -0.23). Mean (SD) PROFFIT-score at baseline was 36.5 (24.9); it was statistically significantly higher for patients living in South Italy, those with lower education level, those who were freelancer/unemployed at diagnosis and those who reported significant economic impact from the COVID-19 pandemic. Mean (SD) scores of determinants ranged from 17.6 (27.1) for item 14 (support from medical staff) to 49.0 (36.3) for item 10 (expenses for medicines or supplements). PROFFIT-score significantly increased with worsening response to determinants., Conclusions: External validation of PROFFIT-score in an independent sample of patients was successful. The instrument is now being used in clinical studies., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Poly ADP-ribose polymerase inhibitors (PARPis) have clinical activity in several cancers. The rationale of their therapeutic use in urothelial cancer (UC) resides in the high homologous-recombination repair (HRR) deficiency (HRD) prevalence and potential cross-sensitivity with platinum-based chemotherapy (PBCT). This review aims to summarize and analyze trials exploring the activity of PARPis in UC, focusing on patients who may benefit from those agents, the best clinical setting for the treatment and the benefit of the association with immune-checkpoint inhibitors (ICIs). We included all the available trials analyzing the activity of PARPis in UC in neoadjuvant, adjuvant, first or subsequent lines, and maintenance setting. We included PARPis in monotherapy and in association with other agents. The results in the maintenance setting are intriguing: ATLANTIS trial showed signals of improved progression-free survival in patients with known HRR aberrations, although the Meet-URO12 trial, with its negative results, suggested the failure of clinical selection based on platinum sensitivity only. Single-agent PARPis in pretreated patients showed discouraging results in an unselected population of chemo-refractory patients. Concerning the association of PARPis with ICIs, several trials are exploring their role in platinum-naïve setting; the results in the advanced setting were globally negative. Prior selection of HRD status is essential to identify patients who might benefit from PARPis. The ideal clinical settings seem to be the maintenance treatment and the combination with ICIs in platinum-naïve patients. Definitive results of ongoing and further trials will delineate the position for PARPis, if any, in UC therapy., Competing Interests: Disclosure All authors declare no support from any organization for the submitted work; MDM reports honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, GlaxoSmithKline, Amgen, Merck, Takeda for consultancy or participation to advisory boards and direct research funding from Tesaro/GlaxoSmithKline, institutional funding for work in clinical trials/contracted research from Beigene, Exelixis, MSD, Pfizer and Roche; other authors declare no conflicts of interest that could appear to have influenced the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Transgender and gender-diverse (TGD) population represents an underserved group across the cancer care continuum. To assess the perspective of both oncology health care providers (OHPs) and TGD individuals in Italy, we conducted two national surveys: one among 2407 OHPs about their attitudes, knowledge and behavior toward TGD patients, and one among TGD persons about their health needs, experiences and barriers encountered in the use of health services across the cancer continuum., Materials and Methods: The surveys were self-compiled web-based computer-aided web interview, conducted in Italy within the 'OncoGender-Promoting Inclusion in Oncology' project, led by the Italian national cancer society [Associazione Italiana di Oncologia Medica (AIOM)]-associated researchers. All members of AIOM were invited by e-mail to participate in the OHP survey. TGD persons were reached through advocacy groups and consumers' panel. The recruitment was completed on a voluntary basis. Survey data were collected and managed using an online platform managed by ELMA Research, an independent pharmaceutical marketing agency., Results: A total of 305 OHPs (13% of AIOM members) and 190 TGD individuals participated in the surveys. Only 19% of OHPs felt competent in providing care to TGD patients and 21% declared not to feel comfortable in treating TGD patients. Seventy-one percent of TGD persons reported that they had never joined any cancer screening program; 32% reported one or more acts of discrimination by health care providers. Seventy-two percent of OHPs recognized the lack of specific education on cancer care for TGD patients and deemed it necessary to receive adequate training., Conclusions: A general lack of knowledge among OHPs about TGD health issues seems to be the main driver of difficulties in providing assistance and of discriminatory attitudes against TGD individuals. Ultimately, this whole issue generates access barriers and contributes to lack of trust in health care services. Educational interventions and an implementation of person-centric cancer policies are urgently needed., Competing Interests: Disclosure ML acted in a consulting/advisory role for Roche, Novartis, Lilly, Pfizer, Merck Sharp and Dohme (MSD), Seagen, Gilead, Exact Sciences, AstraZeneca and received speakers’ honoraria from Takeda, Ipsen, Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Knight. FPe reports grants from Roche and Pfizer; personal fees from Sandoz, Celgene, Pierre Fabre and Janssen Cilag; grants and personal fees from Incyte and AstraZeneca; and grants, personal fees and non-financial support from Bayer. NLV reports grants from Eisai; speaker bureau from GSK; travel expenses for conferences from Gentili, Celgene, Pfizer; advisory role from Novartis and Celgene; advisor role, travel expenses for conference from Pfizer; advisory board from MSD, Roche, Novartis and Astrazeneca. DD reports grants from Gentili, and travel expenses from Roche, Gentili and Eisai. FM has served as speaker for Servier. MDM received honoraria from Pfizer, Takeda, AstraZeneca, Janssen, Eisai, Novartis, Roche, Astellas Pharma, MSD; research grants from Tesaro and GlaxoSmithKline; acted in a consulting/advisory role for AstraZeneca, Pfizer, Takeda, Janssen, Eisai, Novartis, Roche, MSD, Amgen. FPi received honoraria from Amgen, Merck-Serono, Sanofi, Lilly, Bayer, Servier, Astrazeneca, MSD, BMS, Astellas, Organon, Pierre-Fabre; research grants from Astrazeneca, BMS, Incyte, Agenus. RB received honoraria and/or research grant from BI, EISAI, MSD, Amgen, Roche, Pfizer, Astra Zeneca, Lilly, GSK, BMS. GDB received honoraria and/or research grants from Roche, MSD, Tahio, Servier, Celgene, Ipsen, Sanofi; acted in consultory/advisory role for Roche, Lilly, Eisai, Incyte; has served as speaker for Servier, Clovis Oncology, Ipsen, Lilly, Merck Serono, Amgen, Novartis, BMS. MM declares ELMA is a for-profit agency. All other authors have declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Patients with cancer have a well-known and higher risk of vaccine-preventable diseases (VPDs). VPDs may cause severe complications in this setting due to immune system impairment, malnutrition and oncological treatments. Despite this evidence, vaccination rates are inadequate. The Italian Association of Medical Oncology [Associazione Italiana di Oncologia Medica (AIOM)] has been involved in vaccination awareness since 2014. Based on a careful review of the available data about the immunogenicity, effectiveness and safety of flu, pneumococcal and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we report the recommendations of the AIOM about these vaccinations in adult patients with solid tumors. The AIOM recommends comprehensive education on the issue of VPDs. We believe that a multidisciplinary care model may improve the vaccination coverage in immunocompromised patients. Continued surveillance, implementation of preventive practices and future well-designed immunological prospective studies are essential for better management of our patients with cancer., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Subgroup analyses of randomized controlled trials are very common in oncology; nevertheless, the methodological approach has not been systematically evaluated. The present analysis was conducted with the aim of describing the prevalence and methodological characteristics of the subgroup analyses in randomized controlled trials in patients with advanced cancer., Methods: A systematic literature search using PubMed was carried out to identify all phase III randomized controlled trials conducted in adult patients affected by locally advanced or metastatic solid tumours, published between 2017 and 2020., Results: Overall, 253 publications were identified. Subgroup analyses were reported in 217 (86%) publications. A statistically significant association of presence of subgroup analysis with study sponsor was observed: subgroup analyses were reported in 157 (94%) for-profit trials compared with 60 (70%) non-profit trials (P < 0.001). Description of the methodology of subgroup analysis was completely lacking in 82 trials (38%), only cited without methodological details in 100 trials (46%) and fully described in 35 trials (16%). Forest plot of subgroup analyses for the primary endpoint was available in 195 publications (77%). Among publications with reported forest plots, the median number of subgroups for primary endpoint was 19 (range 6-78). Out of the 217 publications with subgroup analyses, authors discuss the heterogeneity of treatment effect among different subgroups in 173 publications (80%), although a formal test for interaction for subgroup analysis of primary endpoint was reported for at least one variable only in 60 publications (28%). Correction for multiplicity was explicitly carried out only in nine trials (4%)., Conclusions: The very high prevalence of subgroup analyses in published papers, together with their methodological weaknesses, makes advisable an adequate education about their correct presentation and correct reading. More attention about proper planning and conduction of subgroup analysis should be paid not only by readers, but also by authors, journal editors and reviewers., Competing Interests: Disclosure The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: MDM reports personal fees from AstraZeneca, Pfizer, Novartis, Roche, Takeda, Janssen, Eisai, Astellas, Merck Sharp & Dohme (MSD), Boehringer Ingelheim, grants from Tesaro-GlaxoSmithKline, outside the submitted work. FP reports grants and personal fees from Bayer, AstraZeneca, Pierre Fabre, Roche, Incyte, MSD, Janssen Cilag, personal fees from Daichii Sankyo, Clovis, Bristol Myers Squibb, Astellas, Ipsen, Seagen, Eli Lilly, GlaxoSmithKline, grants from Tesaro, Pfizer, Exelixis, Aileron, outside the submitted work. MLR had a role as a consultant for Eli Lilly, AstraZeneca and MSD outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinical trials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity and efficacy of these agents and explore differences in clinical outcomes related to RAS/RAF mutational status., Methods: In March 2022, we searched Pubmed, Web of Science, Scopus, and the major conference proceedings (ASCO, ESMO) for randomized and non-randomized clinical trials evaluating MEKi as single agent in recurrent LGSC. The screening was performed independently by two reviewers. Objective response rate (ORR) and progression-free survival (PFS) data were extracted, and RevMan 5.3 software was used for statistical analysis., Results: A total of 4 clinical trials involving 648 patients were included. In the intention-to-treat population, use of a MEK inhibitor was not associated with a significant improvement in PFS, with a pooled Hazard Ratio equal to 0.75 (95 % CI: 0.30 - 1.86, P = 0.54). Heterogeneity was significant (I 2  = 92 %; P = 0.0004). In the overall study population, the pooled odds ratio of ORR for MEKis compared to control treatment was 2.61 (95 % CI: 0.65 - 10.54, P = 0.18). Specifically, ORR was 20.12 % in patients treated with MEKis compared to 9.09 % in women receiving standard treatment. Heterogeneity was significant (I 2  = 85 %; P = 0.009)., Conclusions: Although no statistically significant improvement in PFS was demonstrated, the available data show clear signals of activity, at least for some MEKis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Androgen-deprivation therapy (ADT) historically represented the milestone for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Recently, combining androgen receptor-targeted agents (ARTA) or docetaxel with ADT significantly improved clinical outcomes in this setting. The efficacy of the combined use of an ARTA with docetaxel and ADT (triplet), however, was unknown, and often conflicting data derived from subgroup analysis of randomized phase III trials. In order to better define the benefits and risks of the triplet in mHSPC, we carried out a systematic review and meta-analysis of available clinical trials., Methods: A literature search with no data restriction using Medline/PubMed, the Cochrane Library, and American Society of Clinical Oncology/European Society for Medical Oncology (ASCO/ESMO) Meeting abstracts was carried out up to April 2022. The meta-analysis was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statements. Overall survival (OS) was the primary endpoint; progression-free survival (PFS) and safety were secondary endpoints. For OS and PFS, summary hazard ratios (HRs) were calculated; for safety, risk ratio (RR) was assessed. Random- or fixed-effects models were used, depending on studies heterogeneity., Results: Five randomized clinical trials fulfilled the prespecified inclusion criteria. The triplet significantly improved OS (fixed-effect, HR = 0.74; P < 0.00001) and PFS (fixed-effect; HR = 0.50 for clinical PFS, HR = 0.49 for radiological PFS; P < 0.0001) compared with docetaxel plus ADT. We did not show heterogeneity between treatment efficacy and the disease burden, metachronous versus synchronous presentation, concomitant versus sequential strategy. Compared with docetaxel + ADT, the triplet did not increase the risk of adverse events (AEs) (RR = 1.00, P = 0.27 for any-grade AEs; RR = 1.13, P = 0.14 for severe AEs), except for severe hypertension (RR = 1.73, P = 0.001)., Conclusions: Emerging evidence supports the combination of an ARTA plus docetaxel and ADT in mHSPC patients. Given the availability of several strategies in this setting, clinical characteristics and drug safety profile may help clinicians select the appropriate treatment for mHSPC patients who are more likely to benefit from treatment intensification., Competing Interests: Disclosure None declared., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units., Patients and Methods: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out., Results: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months)., Conclusion: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure MDM reports honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, Takeda for consultancy or participation to advisory boards and direct research funding from Tesaro/GlaxoSmithKline, institutional funding for work in clinical trials/contracted research from Beigene, Exelixis, MSD, Pfizer and Roche; EB reports institutional research funding from the United States National Cancer Institute and Patient-Centered Outcomes Research Institute (PCORI), payments for activities as an Associate Editor for the Journal of the American Medical Association (JAMA), and payments as a scientific advisor from the Research Triangle Institute, AstraZeneca, Carevive, Sivan, Navigating Cancer, Resilience and N-Power Medicine; FD has reported personal fees as an invited speaker from AstraZeneca, Bristol Myers Squibb (BMS), Chugai, Ipsen, Merck and Takeda; personal fees for advisory board membership of Roche; institutional fees for advisory board membership received from Sivan, institutional receiver was Hyperion and advisory board membership stopped 14 April 2020; member of Board of Directors for Kelindi (institutional receiver, Hyperion); institution (Hyperion) has participations and stocks in Kelindi (non-oncological software editor) and in the National Institut of e-Health; he has also reported non-remunerated activities as a member of ASCO; LJF reports honoraria from Genomic Health, Novartis, Eli Lilly, prIME a Medscape Oncology Company, Pfizer, Sobi, MSD, 3P Solution, Veracyte, Voluntis and AstraZeneca for consultancy/participation on advisory boards. Also, grant funding from Veracyte, Eli Lilly, Roche and BMS; PAG reports honoraria from InformedDNA as member of Scientific Advisory Board, Oxford University Press as Editor-in-Chief of the Journal of the National Cancer Institute, royalties from Up-to-date as section editor on Cancer Survivorship, institutional funding for work in clinical trials/contracted research from Blue Note Therapeutics, consultant for Grail and Blue Note Therapeutics and non-remunerated leadership roles for the Breast Cancer Research Foundation as member of Scientific Advisory Board; DH reports honoraria for consultancy and participation on the scientific advisory board of Carevive Systems, institutional funding for work on clinical trials from AstraZeneca and contracted research funding from the Leukemia and Lymphoma Society of Canada, contractual payment from York University, ON, Canada for course development and teaching; CK is a full-time employee of the German Cancer Society, a non-profit. He reports non-remunerated leadership roles for the non-profits German Association of Medical Sociology (board of directors, treasurer) and the German Network on Health Services Research (section chair, oncology section); FP reports honoraria from Bayer, Pierre Fabre, AstraZeneca, Incyte, Ipsen, Clovis, Astellas, Sanofi, institutional funding for work in clinical trials/contracted research from Roche, Bayer, AstraZeneca, Pfizer, Incyte, Tesaro/GlaxoSmithKline, Merck, non-remunerated leadership roles for Associazione Italiana di Oncologia Medica – AIOM (future President); AMS reports honoraria from the Association of Community Cancer Centers, Pfizer, Genentech, Purchaser Business Group on Health, and Henry Ford Cancer Center, a financially compensated leadership role in Navigating Cancer (consultant in 2021 for less than 5000 USD), institutional funding for work in clinical trials/contracted research from Sivan Innovation and UroGen Pharma Ltd, and grant funding from PCORI, National Institutes of Health, Agency for Healthcare Research and Quality, Bladder Cancer Advocacy Network, Hematology/Oncology Pharmacy Association, Cancer and Aging Research Group; PS reports non-remunerated leadership roles with the Trans Tasman Radiation Oncology Group, Clinical Oncology Society of Australia and Head and Neck Cancer Australia; JFD reports honoraria from International Association for the Study of Lung Cancer (invited speaker), Fred Hutchinson Cancer Research Center (PCORI project), Genentech (advisory board), Pfizer (advisory board); financial compensation from International Association for the Study of Lung Cancer (independent consultant) and the United States government as a special employee and member of the Secretary's Advisory Committee for Human Research Protections (SACHRP); non-remunerated activities for LUNGevity (Scientific Advisory Board), National Cancer Institute (scientific panels); non-remunerated leadership roles for The ROS1ders (Vice President, Board Chair); and non-remunerated membership or affiliation with the International Association for the Study of Lung Cancer, American Society of Clinical Oncology, American Association for Cancer Research, Nuvalent, AnHeart Therapeutics and Turning Point Therapeutics; CIR reports honoraria from Kyowa Kirin, Molteni Pharma Spa, Mundipharma and Angelini Pharma for educational events and invited speaker; LW, LZ, KA and DS have declared no potential conflicts of interest.

Herpes zoster (HZ) is the infectious reactivation of the varicella-zoster virus. HZ is more frequent in immunocompromised subjects, including patients with cancer. HZ complications can even last for years with a consequent delay in treatment of the underlying malignancy and with an unfavorable impact on quality of life. Nowadays, HZ is a vaccine-preventable disease: the recent approval of adjuvanted glycoprotein E-based recombinant zoster vaccine has changed preventive perspectives in immunocompromised subjects. Recombinant zoster vaccine induced both strong humoral and cellular immune responses also in immunocompromised patients. The question is, therefore, to which categories of cancer patients we should recommend HZ vaccination. Based on a careful review of the available data present in the literature, including recommendations and expert opinions, we report the position of the Associazione Italiana di Oncologia Medica on HZ vaccination in adult patients with solid tumors, thus providing clinical practice advice in a field where clear-cut information is missing., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has severely affected cancer care and research by disrupting the prevention and treatment paths as well as the preclinical, clinical, and translational research ecosystem. In Italy, this has been particularly significant given the severity of the pandemic's impact and the intrinsic vulnerabilities of the national health system. However, whilst detrimental, disruption can also be constructive and may stimulate innovation and progress. The Italian Association of Medical Oncology (AIOM) has recognized the impact of COVID-19 on cancer care continuum and research and proposes the '2021 Matera statement' which aims at providing pragmatic guidance for policymakers and health care institutions to mitigate the impact of the global health crisis on Italian oncology and design the recovery plan for the post-pandemic scenario. The interventions are addressed both to the pillars (prevention, diagnosis, treatment, follow-up, health care professionals) and foundations of cancer care (communication and care relationship, system organization, resources, research, networking). The priorities to be implemented can be summarized in the MATERA acronym: Multidisciplinarity; Access to cancer care; Telemedicine and Territoriality; Equity, ethics, education; Research and resources; Alliance between stakeholders and patients., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM-AIRO-AISP-ANISC-AURO-Fondazione AIOM-SIAPEC/IAP-SIBioC-SICO-SIF-SIGE-SIGU-SIU-SIURO-UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations., Competing Interests: Disclosure LC: honoraria for presentations from Astra Zeneca, Pfizer, Novartis, MSD; support for attending meetings from AstraZeneca; advisory board of Astra Zeneca, Novartis, MSD, Gilead. UDG: consulting fees from AstraZeneca, Pfizer, MSD, BMS, Ipsen, Novartis, Astellas, Janssen, Bayer, PharmaMar, Eisai, and Clovis. MDM: grants from any entity from Tesaro, GlaxoSmithKline; consulting fees from Novartis, Roche, AstraZeneca, Merck Serono, Pfizer, Merck Sharp & Dohme, Janssen, Eisai, Takeda, Boehringer Ingelheim, and Servier; honoraria for presentations from Novartis, Roche, AstraZeneca, Pfizer, Merck Sharp & Dohme, Janssen, Astellas, Boehringer Ingelheim; serves on the advisory board of Merck Sharp & Dohme, Amgen, Janssen, and Astellas. MG: honoraria for presentations from MSD. BAJF: honoraria for presentations from Janssen, Ferring, Bayer, Roche, Astellas, Elekta, Carl Zeiss, Ipsen, Accuray, and IBA. AL: consulting fees from Astellas, Jansen, and Bayer. AR: advisory boards of Bristol, Pfizer, Bayer, Kyowa Kirin, Ambrosetti; and honoraria for presentations from Roche Diagnostic and AstraZeneca. All other authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

For decades metastatic squamous cell carcinoma of the anus (SCCA)has been considered a rare disease with very limited treatment options and a dismal prognosis. Prior to 2017, no data from prospective studies on the management of metastatic SCCA were available with scant information from retrospective analyses and few treatment options. Recently, InterAAct trial showed an advantage of carboplatin plus paclitaxel over the historical standard of care represented by cisplatin plus 5-fluorouracil. Unfortunately, there is no established second-line treatment after progression to first-line platinum-based chemotherapy. Interestingly, a better understanding of the immunobiology of the neoplasm and the strict association between HPV/HIV infection and tumor microenvironment led to the development of immunotherapies. Emerging evidence suggests that the use of anti-PD1/PD-L1 agents could lead to promising antitumor activity in a subgroup of patients with pre-treated anal cancer, opening new therapeutic scenarios. Here, we will focus on completed clinical trials evaluating immunotherapy in patients with (SCCA), pointing out the future perspectives and possible biomarkers of response., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Retrospective series suggest that bevacizumab-induced hypertension (HTN) is a prognostic and potentially predictive biomarker of efficacy of the antiangiogenic drug in the upfront treatment of metastatic colorectal cancer (mCRC) patients. The immortal-time bias and the effect of pre-existing HTN might affect these findings. We conducted a pooled, post hoc analysis of 2 prospective randomized trials of chemotherapy plus bevacizumab in mCRC, and performed a systematic review of the available literature focusing on how the immortal-time bias was taken into account and how pre-existing HTN potentially requiring the use of antihypertensive drugs was managed., Methods: The pooled-analysis included patients enrolled in the phase III TRIBE and TRIBE-2 studies that compared upfront FOLFOXIRI + bevacizumab to FOLFIRI or FOLFOX + bevacizumab, respectively. Association between HTN and survival outcomes was assessed by incorporating a time-dependent Cox regression model to consider the time-dependency of the probability of HTN onset during the treatment. The systematic review was conducted according to PRISMA guidelines., Results: The systematic review retrieved 14 eligible and highly heterogeneous studies. A positive prognostic impact of bevacizumab-induced HTN was reported in the 58% of the analyses reporting Progression Free Survival (PFS) and in the 54% of the analyses reporting Overall Survival (OS) data. Immortal-time bias was incorporated in 4 studies (28%). In TRIBE and TRIBE-2 study populations (N = 1175), patients experiencing ≥ G2 HTN during first-line bevacizumab administration showed longer PFS (median: 14.7 versus 10.3 months, p < 0.001) and OS (median: 31.7 versus 24.2 months, p < 0.001). The association with OS retained statistical significance after correction for time-dependency (p = 0.003) and was confirmed in the multivariable model including HTN as a time-dependent variable (p = 0.02). Moreover, in patients with pre-existing HTN, no difference in terms of PFS and OS was observed compared with the subgroup of patients who never experienced ≥G2 HTN (HR 1.01, p = 0.86 and HR 1.02, p = 0.78 respectively., Conclusions: Bevacizumab-induced HTN during the first-line treatment of mCRC is an independent prognostic factor, also adopting a time-dependency correction. Toxicity should be interpreted as a time-dependent variable when exploring its association with clinical outcome., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: To assess the performance of the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria in stratifying the risk of bleeding and ischaemic events after percutaneous coronary intervention (PCI)., Methods: MEDLINE, COCHRANE, Web of Sciences, and SCOPUS were searched for studies aimed at validating the ARC-HBR criteria in patients treated with PCI. The primary outcome measure of this meta-analysis was major bleeding., Results: The analysis included 10 studies encompassing 67,862 patients undergoing PCI; the HBR definition was fulfilled in 44.7% of the cases. The risk of major bleeding was significantly higher in HBR vs. Non-HBR group (RR, 2.56, 95% CI 2.28-2.89). The average C-statistic was 0.64 (95% CI 0.60-0.68), indicating modest discrimination. The risk of intracranial hemorrhage, gastrointestinal bleeding, fatal bleeding, ischaemic stroke, cardiac death and all-cause death was higher in HBR vs. Non-HBR group. Despite a higher incidence of myocardial infarction and stent thrombosis in patients deemed at HBR, the rate of target lesion revascularization was comparable between groups (RR, 1.01, 95% CI 0.88-1.16). The mean effect size for the cumulative incidence of major bleeding exceeded the HBR cut-off value of 4% for all major criteria except one, and for two out of six minor criteria, namely age ≥ 75 years and moderate CKD., Conclusion: The ARC-HBR definition identifies patients at higher risk of major bleeding and other adverse cardiovascular events after PCI. Almost all major criteria, but also two of the minor criteria, were individually associated with rates of major bleeding above 4% thus fulfilling the definition of major HBR criteria., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The safety and efficacy outcome of elderly metastatic colorectal cancer (mCRC) patients fit enough to receive combination chemotherapy plus biological agents is an issue of growing interest. Also, gender-specific differential toxicity and efficacy of anti-epidermal growth factor receptor (EGFR)-based upfront treatments need to be explored., Patients and Methods: Valentino was a multicenter, randomized, phase II trial, investigating two panitumumab-based maintenance strategies following first-line panitumumab plus FOLFOX in RAS wild-type mCRC patients. We carried out a subgroup analysis, aimed at assessing the differences in efficacy, safety and quality of life (QoL) according to age (<70 versus ≥70 years) and gender (male versus female). Efficacy endpoints were progression-free survival (PFS), overall survival (OS) and overall response rate (ORR); safety endpoints were rates of any grade and grade 3/4 adverse events (AEs)., Results: No significant differences in terms of PFS, OS and ORR were observed between patients aged <70 or ≥70 years and the effect of the maintenance treatment arm on survival outcomes was similar in the two subgroups. The safety profile of both induction and maintenance treatment and the impact on QoL were similar in elderly and younger patients. No significant differences in PFS, OS, ORR or clinical benefit rate were observed according to gender. A significantly higher rate of overall grade 3/4 AEs (P = 0.008) and of grade 3/4 thrombocytopenia (P = 0.017), any grade and grade 3/4 neutropenia (P < 0.0001) and any grade conjunctivitis (P = 0.033) was reported in female as compared to male patients. Conversely, we reported a significantly higher incidence of any grade skin rash (P = 0.0007) and hypomagnesemia (P = 0.029) in male patients., Conclusions: The upfront choice of an anti-EGFR-based doublet chemotherapy followed by a maintenance strategy represents a valuable option in RAS wild-type mCRC irrespective of gender and age, though a careful evaluation of patients to maximize the risk/benefit ratio is warranted., Competing Interests: Disclosure FP has received honoraria for speaker activities and participation in advisory boards from Sanofi, Amgen, Bayer, Merck-Serono, Lilly, Roche and Servier and research grants from BMS. SL has received honoraria for speaker activities and participation in advisory boards from Amgen, Bayer, Merck-Serono, Roche, Servier and Bristol-Myers Squibb. AZ has received honoraria for speaker bureau from Amgen, Merck, Servier and Bayer. SC has received honoraria for participation in advisory boards from Merck. MDB has received honoraria for speaker activities and participation in advisory boards from Amgen, Roche, Lilly, Servier, Incyte and Celgene. FM has received honoraria for speaker activities from Servier. The remaining authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

High mortality rates in elderly patients or in those with underlying chronic illnesses and/or a compromised immune system is a peculiar feature of COVID-19 infection. The possible coexistence of a cancer and COVID-19 infection in the same individual prompted concerns regarding their synergistic effect on prognosis. In order to balance patients' needs with the risks related to the infection, the question oncologists have asked from the beginning of the first wave of the pandemic has been: 'how can we deal with COVID-19 infection in cancer patients?' In pursuing its mission, the Associazione Italiana Oncologia Medica (AIOM) has made every possible effort to support cancer patients, health care professionals and institutions in the decision-making processes the pandemic has engendered within this scenario. The relevant documents as well as the educational and institutional initiatives the AIOM has taken are reported in this article., Competing Interests: Disclosure NS has served as a consultant for Celgene and Isheo; MDM has served as a consultant for AstraZeneca, Takeda, Pfizer, Novartis, Roche, Janssen, Astellas, Elisai; UDG has served as a consultant for Janssen, Astellas Pharma, Sanofi, Bayer, Pfizer, Bristol-Myers Squibb (BMS), Novartis, Ipsen, and Merck Sharp & Dohme (MSD); MT has served as a consultant for Janssen, Astellas Pharma, Sanofi, Bayer, Pfizer, Novartis; DG has served as a consultant for Pfizer, Ipsen, Novartis, Merck; RC has served as a consultant for Novartis, Pfizer, Roche, Takeda, AstraZeneca, BMS, MSD; NLV has served as a consultant for Novartis, Pfizer, Roche, Gentili, Celgene, EISAI, MSD; LDM has served as a consultant for Roche, Novartis, Eli Lilly, Pfizer, MSD, Ipsen, Takeda, Celgene, Eisai, Genomic Health, General Electrics, Amgen, Pierre Fabre, Daiichi Sankyo, AstraZeneca; FP has served as consultant for Roche, Bayer, AstraZeneca, Pierre Fabre, Janssen Cilag, Ipsen; SC has served as consultant for Eli Lilly; GB has served as consultant for Roche, Servier, Celgene, Ipsen, Sanofi, Merck Serono. AR has declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To evaluate if the pandemic mitigation effects of lockdown in Italy have been influenced by the level of penetration of COVID-19 in Italian Regions at the onset of containment (March 9, 2020)., Methods: We collected data published day by daily from the first COVID-19 case until May 3, 2020, the end of lockdown, by Italy's Protezione Civile Department. Linear regression analyses were performed to evaluate possible correlations between the number of confirmed cases/100.000 residents and the number of new cases/100.000/day before lockdown, with the number of deaths/100.000 residents at sixty days, in each Italian region., Results: We found a significant positive correlation between the number of confirmed cases before lockdown and mortality up to sixty days (p < 0.001; R 2 = 0.57) as well as between the incidence rate of new cases per day and mortality up to sixty days (p < 0.001; R 2 = 0.73). Regression coefficients indicated about two deaths up to sixty days for every new patient with confirmed COVID-19 before lockdown, and 37 deaths for every new infected subject per day until the lockdown decree of March 9, 2020., Conclusions: Every new infected subject before lockdown counted on the death toll of the COVID-19 pandemic in Italy., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The combination of chemotherapy plus anti HER-2 agents is the mainstay of HER-2 positive advanced breast cancer (ABC) therapy. We conducted a phase II trial testing activity and safety of trastuzumab and metronomic capecitabine/cyclophosphamide (HEX) as first-line therapy in HER-2 positive ABC.
Methods. Patients at first relapse or with synchronous metastasis were treated with trastuzumab (4 mg/kg, biweekly) plus oral capecitabine (1500 mg/daily) and cyclophosphamide (50 mg/daily). Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival (PFS), clinical benefit rate (CBR; PR + CR + SD for ≥ 24 weeks) and tolerability. Optimal two-stage design was applied., Results: Sixty patients with measurable ABC, tumors scored as +3 for HER-2 or FISH +, untreated for advanced disease were enrolled. Median age was 62.5 years, visceral metastases were present in most patients (57.9%). Median number of cycles was 16 (range 1-98). ORR was 56.7% (95% CI, 44.1-68.4%), with 5 CR (8.3%) and 29 PR (48.3%). Fifteen patients had SD (25%). The CBR was 78.2%. Nine progressions were observed (15%). Median PFS was 11 months. One year PFS was 47.7%. Median OS was 45.9 months. Worst toxicities were grade 3 hand-foot syndrome in 2 pts (3.3%), grade 3 anaemia in 2 pts (3.3%), grade 2 nausea in 2 pts (3.3%) and grade 3-4 diarrhea in 2 pts (3.3%). Cardiac toxicity grade 1 was reported in 1 pt., Conclusions: Combination of trastuzumab and metronomic oral chemotherapy has clinical activity. The tolerability was excellent and allowed the prolonged delivery of treatment., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Anticancer drugs can interact with the tumour microenvironment and their effects could be exploited to favour anticancer immune response. Eribulin contributes to tumour vasculature remodelling and transforming growth factor β (TGF-β) modulation in experimental models and in humans. We performed a prospective, translational, exploratory analysis of the levels of circulating cytokines at different time points in patients with metastatic breast cancer treated with eribulin., Methods: TGF-β, tumour necrosis factor α, vascular endothelial growth factor, IL-6, IL-8, IL-10, IL-21 and C-C motif chemokine ligand-2 levels were assessed in peripheral blood samples obtained from seven healthy volunteers and 41 patients at baseline (T 0 ), after four cycles of eribulin (T 1 ) and at disease progression (T PD ). Baseline values and longitudinal changes in cytokine levels were then related to clinical outcome., Results: In the 41 patients, high IL-6 and IL-8 (above the median) at T 0 significantly correlated with worse survival. At T 1 , IL-21 significantly decreased in patients with T PD within the fourth course of treatment, compared with patients without progression. TGF-β and IL-8 above the median and IL-21 below the median at T 1 significantly correlates with worse progression free survival (PFS). Patients exhibiting an increase of TGF-β or a decline of IL-21 between T 0 and T 1 showed a significantly worse PFS. Multivariate Cox regression analysis showed that only plasma TGF-β changes at T 1 correlated with survival. At T PD, TGF-β significantly increased in all patients., Conclusions: We observed a significant correlation between TGF-β decline during eribulin treatment and outcome in patients with metastatic breast cancer. Altogether, our data suggest that eribulin treatment might interfere with the tumour microenvironment., Competing Interests: Competing interests: OG reports grants from Eisai, during the conduct of the study; personal fees from Eisai, personal fees from Pfizer, personal fees from Novartis, personal fees and other from Celgene, personal fees from Amgen, other from Roche, outside the submitted work; AM reports personal fees and other from Eisai, personal fees and other from Novartis, personal fees from Astra Zeneca, personal fees from Teva, personal fees from Pfizer, personal fees and other from Celgene, other from Ipsen, outside the submitted work; FM reports personal fees and other from Roche, personal fees from Novartis, personal fees from Pfizer, personal fees from Eli Lilly, outside the submitted work; AMV reports personal fees from Pierre Fabre, personal fees and other from Celgene, personal fees from Epionpharma, other from Roche, other from Eli Lilly, other from Bristol Myers Squibb, other from Pfizer, outside the submitted work; PV reports personal fees and other from Bristol Myers Squibb, personal fees from Pierre Fabre, other from Janssen, other from Roche, other from Pfizer, other from Novartis, other from Astellas, outside the submitted work; MDM reports personal fees from Merck Sharp & Dohme, personal fees from Bristol Myers Squibb, personal fees from Eisai, personal fees from Janssen, personal fees from Astellas, personal fees from Astra Zeneca, personal fees from Pfizer, personal fees from Takeda, grants from Tesaro, outside the submitted work; MM reports personal fees and other from Astra Zeneca, personal fees and other from Merck Serono, personal fees and other from Bristol Myers Squibb, personal fees from Merck Sharp & Dohme, personal fees and other from Pfizer, outside the submitted work; the remaining authors declare no competing interests., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: Other than the programmed cell death ligand 1 (PD-L1) value, oncologists have only the clinical characteristics of patients with advanced non-small-cell lung cancer (aNSCLC) to determine candidates for immunotherapy. A clinical prognostic score composed of the Eastern Cooperative Oncology Group performance status, sex, histologic type, stage, platinum-based first-line therapy, and response to first-line therapy has categorized 3 prognostic groups for patients undergoing second-line chemotherapy. We sought to validate the same score for patients with aNSCLC treated with second- or further-line immunotherapy., Materials and Methods: We collected data from 2 Italian centers. A score was generated to divide patients into 3 prognostic groups: best, score < 5; intermediate, score 5 to 9; and worst, score > 9. Overall survival (OS) and progression-free survival (PFS) were the endpoints., Results: A total of 347 patients were included for analysis. Their median age was 66 years (range, 30-88 years), most were aged < 70 years (67.5%), 70.7% were men, 79.5% were smokers, and 74.6% had had adenocarcinoma. The Eastern Cooperative Oncology Group performance status was 0 for 23%, 1 for 54.5%, and 2 for 22.5%. Of the 347 patients, 28% were in the best prognosis, 51% in the intermediate, and 21% in the worst prognosis group, respectively. The median OS was 18.0 months for the best, 8.5 months for the intermediate (hazard ratio [HR] vs. best, 1.83; 95% confidence interval [CI], 1.35-2.47; P < .001) and 2.6 months for worst (HR vs. best, 5.77; 95% CI, 3.99-8.33; P < .001) group. The median PFS was 3.4 months for the best, 3.7 months for the intermediate (HR vs. best, 1.35; 95% CI, 1.03-1.77; P = .032), and 1.9 months for the worst (HR vs. best, 2.51; 95% CI, 1.80-3.50; P < .001) group., Conclusions: The prognostic score was able to predict the outcomes of patients with aNSCLC who had received immunotherapy. The worst category showed a dismal life expectancy and probably would not benefit from active systemic therapy. Thus, for these patients, best supportive care could be the best choice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Little is still known about the clinical features associated with the occurrence of acute respiratory distress syndrome (ARDS) in hospitalized patients with Coronavirus disease 2019 (COVID-19). The aim of the present study was to describe the prevalence of pre-admission antithrombotic therapies in patients with COVID-19 and to investigate the potential association between antithrombotic therapy and ARDS, as disease clinical presentation, or in-hospital mortality. We enrolled 192 consecutive patients with laboratory-confirmed COVID-19 admitted to emergency department of five Italian hospitals. The study population was divided in two groups according to the evidence of ARDS at chest computed tomography at admission. Propensity score weighting adjusted regression analysis was performed to assess the risk ARDS at admission, and death during hospitalization, in patients treated or not with antiplatelet and anticoagulant agents. ARDS was reported in 73 cases (38 %), who showed more likely hypertension compared to those without ARDS (57.8 % vs 49.6 %; P = 0.005). Thirty-five patients (18.5 %) died during the hospitalization. Not survived COVID-19 patients showed a statistically significant increased age (77 ± 8.31 vs 65.57 ± 8.31; P = 0.001), hypertension (77.1 % vs 53.5 %; P = 0.018) and coronary artery disease prevalence (28.6 % vs 10.2 %; P = 0.009). Both unadjusted and adjusted regression analyses showed no difference in the risk of ARDS at admission, or death during hospitalization, between patients treated or not with antiplatelets or anticoagulants. Pre-admission antithrombotic therapy, both antiplatelet and anticoagulant, does not seem to show a protective effect in severe forms of COVID-19 with ARDS at presentation and rapidly evolving toward death., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Biweekly schedule of XELOX-2 (capecitabine plus oxaliplatin) showed interesting results in first-line therapy of patients with metastatic colorectal cancer (mCRC). Bevacizumab plus FOLFOX-4 (oxaliplatin, folinic acid, and infusional 5-fluorouracil) is among standard first-line treatment options in this setting. We performed a phase II randomized trial in order to evaluate the activity of bevacizumab plus either FOLFOX-4 or XELOX-2 in first-line therapy of patients with mCRC., Materials and Methods: Patients with mCRC were randomized, in a 1:2 ratio, to first-line bevacizumab plus either FOLFOX-4 (Arm A), as calibration arm, or XELOX-2 (Arm B), up to 12 cycles. Patients without progression were further randomized to maintenance bevacizumab alone or with the same induction fluoropyrimidine. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival, overall survival, and toxicity. The study design was formally non-comparative, but exploratory comparison was performed., Results: Forty-five patients were randomized in arm A and 87 in arm B with an ORR of 55.6% versus 48.3% (P = .43), respectively. After a median follow-up of 47.2 months, progression-free survival was 10.0 versus 9.9 months (hazard ratio, 0.96; 95% confidence interval, 0.65-1.41; P = .84) and overall survival was 29.8 versus 25.0 months (hazard ratio, 1.21; 95% confidence interval, 0.77-1.92; P = .41), respectively. The main grade 3 to 4 toxicities (% A/B) were: neutropenia 15/3 and nausea 9/5., Conclusion: This exploratory analysis showed that biweekly XELOX-2 plus bevacizumab has a comparable ORR with FOLFOX-4 plus bevacizumab in patients with mCRC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bone health impairment is a frequent detrimental consequence of the high bone tropism of prostate cancer (PCa) cells. It is further worsened by administration of androgen-deprivation therapy (ADT), the current standard of care in the management of advanced PCa, through a rapid and dramatic increase in bone turnover and body mass changes. As a result, patients may experience substantial pain and poor quality of life (QoL) and have an increased risk of death. Notwithstanding the importance of this issue, however, bone health preservation is not yet a widespread clinical goal in daily practice.To address this urgent unmet need, following a thorough discussion of available data and sharing of their clinical practice experience, a panel of Italian experts in the field of bone health and metabolism formulated a number of practical advices for optimising the monitoring and treatment of bone health in men undergoing ADT during all phases of the disease. The rationale behind the venture was to raise awareness on the importance of bone preservation in this complex setting, while providing an instrument to support physicians and facilitate the management of bone health.Current evidence regarding the effects on bone health of ADT, of novel hormone therapies (which improve progression delay, pain control and QoL while consistently carrying the risk of non-pathological fractures in both non-metastatic and metastatic PCa) and of bone turnover inhibitors (whose use is frequently suboptimal) is reviewed. Finally, the expert opinion to optimise bone health preservation is given., Competing Interests: Competing interests: DS reports personal fees from Janssen during the conduct of the study; grants and personal fees from Amgen, Novartis and Astellas; personal fees from Boehringer, Roche and Pfizer outside the submitted work. AB reports personal fees from Janssen-Cilag during the conduct of the study. MDM reports personal fees from Janssen during the conduct of the study; personal fees from Janssen, Bristol Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Takeda, Eisai and Pfizer outside the submitted work. GP reports fees as consultant/for advisory board from Bayer, Janssen, MSD and Novartis. SB reports fees for advisory board from Astellas, Janssen and Bayer. TI reports personal fees from Eisai; other from Novartis, Ipsen and PharmaMar; and grants from Novartis outside the submitted work. FB reports personal fees from Janssen during the conduct of the study, grants and personal fees from Amgen and Abiogen, and grants from Chiesi outside the submitted work., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: Several studies have described a worse prognosis for right-sided colon cancer compared to left-sided. The aim of this study was to compare patterns of recurrence and survival following resection of liver metastases (LM) from right-sided (RS) versus left-sided (LS) colon cancer., Methods: Patients undergoing resection for colon cancer LM between 2000 and 2017 were analyzed. Rectal cancer, multiple primaries and unknown location were excluded., Results: Out of 995 patients, 686 fulfilled inclusion criteria (RS-LM = 322, LS-LM = 364). RS colon cancer had higher prevalence of metastatic lymph nodes (67.4% vs. 57.1%, P = 0.008). RS-LM were more often mucinous (16.8% vs. 8.5%, P = 0.001) and G3 (58.3% vs. 48.9%, P = 0.014). 451 (65.7%) patients experienced recurrence (RS-LM 68.9% vs. LS-LM 62.9%). In RS-LM group, recurrence was more often encephalic (2.3% vs. 0%, P = 0.029) and at multiple sites (34.2% vs. 23.5%, P = 0.012). The rate of re-resection was lower in RS-LM patients (27.9% vs. 37.5%, P = 0.024). Multivariate analysis showed RS-LM to have worse 5-year overall (35.8% vs. 51.2%, P = 0.002) and disease-free survival (26% vs. 43.6%, P = 0.002)., Conclusions: RS-LM is associated with worse survival and aggressive recurrences, with lower chance of re-resection., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Quality of life (QoL) is not included among the end points in many studies, and QoL results are underreported in many phase 3 oncology trials. We performed a systematic review to describe QoL prevalence and heterogeneity in QoL reporting in recently published prostate cancer phase 3 trials. A PubMed search was performed to identify primary publications of randomized phase 3 trials testing anticancer drugs in prostate cancer, issued between 2012 and 2018. We analyzed QoL inclusion among end points, presence of QoL results, and methodology of QoL analysis. Seventy-two publications were identified (15 early-stage, 20 advanced hormone-sensitive, and 37 castration-resistant prostate cancer [CRPC]). QoL was not listed among study end points in 23 studies (31.9%) (40.0% early stage, 40.0% advanced hormone sensitive, and 24.3% CRPC). QoL results were absent in 15 (30.6%) of 49 primary publications of trials that included QoL among end points. Overall, as a result of absent end point or unpublished results, QoL data were lacking in 38 (52.8%) primary publications (53.3% early stage, 55.0% in advanced hormone sensitive, and 51.4% in CRPC). The most commonly used QoL tools were Functional Assessment of Cancer Therapy-Prostate (FACT-P) (21, 53.8%) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) (14, 35.9%); most common methods of analysis were mean changes or mean scores (28, 71.8%), time to deterioration (14, 35.9%), and proportion of patients with response (10, 25.6%). In conclusion, QoL data are lacking in a not negligible proportion of recently published phase 3 trials in prostate cancer, although the presence of QoL results is better in positive trials, especially in CRPC. The methodology of QoL analysis is heterogeneous for type of instruments, analysis, and presentation of results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified., Methods: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome., Results: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule-positive (CD4 + ) programmed death 1-positive (PD-1 + ) (>5.2%) and CD8 + PD-1 + (6.4%) cells, CD4 + lymphocyte activating 3-positive (LAG-3 + ) (>2.8% ) and CD8 + LAG-3 + (>2.8%) cells, CD4 + T cell immunoglobulin and mucin domain 3-positive (TIM-3 + ) (>2.5%), and CD8 + TIM-3 + (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes. The immune phenotype of pleural fluid cells had no prognostic significance. By contrast, the intratumor T-regulatory and MDSC levels significantly correlated with progression-free and overall survival, the PD-1 + /LAG-3 + /TIM-3 + CD4 + tumor-infiltrating lymphocytes correlated with overall survival., Conclusions: A clear immune signature of pleural fluids and tissues of MPM patients may contribute to better predict patients' outcome., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic predictors of outcome in patients with functional mitral regurgitation (FMR) undergoing MitraClip implantation (MCi) are still poorly known. The aim of our study is to identify the baseline predictors of outcome in FMR patients candidate to MCi., Methods: All patients with symptomatic moderate-to-severe or severe FMR undergoing MCi at our institution were consecutively and prospectively enrolled. Baseline clinical and instrumental data were collected. Primary endpoint was the occurrence of cardiac death; secondary endpoints were all-cause death and the composite of cardiac death or rehospitalization for heart failure., Results: 74 patients (mean 71.6 ± 8.3 years) were enrolled. During follow-up (median 416.0 days), the primary endpoint occurred in 15 (20.3%), all-cause death in 26 (35.1%) and the composite endpoint in 25 (33.8%). At multivariate analysis, the left atrial volume index (LAVi; HR:1.02; P = 0.048) and the low peak oxygen uptake (peak VO 2 ; HR:0.73; P = 0.018) increased the risk of cardiac death at follow-up; atrial fibrillation (AF; HR:2.69; P = 0.027) was independently associated to all-cause death and the low level of peak VO 2 was an independent predictor of overall mortality (HR:0.70; P < 0.001) as well as of the composite endpoint (HR:0.73; P < 0.001). The ROC analysis identified a peak VO 2 cut-off of 10.0 mL/kg/min as the best predictor for the three study endpoints; the best LAVi cut-off for cardiac death was 67 mL/m 2 . Kaplan-Meier analysis for the individual and combined outcome predictors confirmed their significant stratification ability during follow-up., Conclusions: Peak VO 2 , along with LAVi and AF, identify FMR patients with the worst prognosis after MCi., (Copyright © 2018. Published by Elsevier B.V.)

Research Question: This study explored the knowledge, attitudes and practice of physicians towards fertility and pregnancy-related issues in young BRCA-mutated breast cancer patients., Design: Physicians attending two international breast cancer conferences completed a 26-item questionnaire exploring fertility preservation, pregnancy during (BCP) or after breast cancer. A statistical comparison was carried out of the responses exploring the same issues in young breast cancer patients overall or specifically in those with BRCA mutations., Results: The survey was completed by 273 physicians. Ovarian tissue cryopreservation (33% versus 40%; P = 0.009) and gonadotrophin-releasing hormone analogues during chemotherapy (74% versus 81%; P = 0.001) were less commonly suggested in BRCA-mutated patients than in the overall breast cancer population. 42% of respondents agreed or were neutral on the statement that ovarian stimulation should not be considered safe in BRCA-mutated breast cancer patients. 45% and 30% agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence in BRCA-mutated patients or in the overall breast cancer population, respectively (P < 0.001). 15% and 3% disagreed that transplanting the cryopreserved ovarian tissue can be considered safe in BRCA-mutated patients or in the overall breast cancer population, respectively (P < 0.001). 33.3% were against the addition of platinum agents as neoadjuvant chemotherapy in BRCA-mutated patients with BCP., Conclusions: Several misconceptions on fertility preservation and pregnancy-related issues in breast cancer patients persist even among physicians directly involved in breast cancer care. Focused research efforts to address these issues in BRCA-mutated breast cancer patients and education to improve physicians' knowledge and adherence to available guidelines are urgently needed., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)