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Background: Vaccination rates are still suboptimal in cancer patients. Oncologists play a central role in recommending vaccines to their patients. Our goal was to investigate vaccine acceptance among cancer patients and understand the factors shaping their choices, thereby aiding physicians in better supporting their patients' vaccination decisions., Methods: We designed a prospective cross-sectional survey exploring vaccination status, attitudes, and reasons for hesitancy towards vaccinations against the main vaccine preventable diseases (VPDs) among patients undergoing active cancer treatment. The primary endpoint was to evaluate the proportion of vaccinated subjects in our cohort of cancer patients. The secondary endpoints were to assess the proportion of vaccinated subjects against different types of VPDs: flu, COVID-19, pneumococcal disease, Herpes Zoster (HZ)., Results: Between 12 February and 01 March 2024, a total of three hundred and seventeen patients with cancer were invited to respond to the survey, 309 of whom (97%) agreed to do it. Two hundred seventy-three patients (0.88, 95% confidence interval [CI] 0.84-0.91) had received at least one vaccination. Two hundred thirty-one patients (74.76%) reported that at their first oncology visit their oncologist recommended vaccinations, primarily anti-flu (92.21%) and anti-SARS-CoV-2 (83.55%) vaccinations, while less frequently the anti-pneumococcal (42.42%) and anti-HZ (37%) vaccines were recommended. On the univariate analysis, age over 75 years (p = 0.041), marital status (p = 0.003) and the oncologist's vaccine recommendation during the first visit (p < 0.001) were significantly associated to vaccine acceptance. At the multivariable analysis, these variables were independently associated with vaccine willingness. Overall in our cancer population, the two main reasons for vaccine hesitancy were the lack of recommendation by the oncologist (55.41%, n = 128) and the lack of awareness of the importance of vaccination in the context of oncological care (49.35%, n = 114)., Conclusions: This survey emphasizes the importance of vaccine counseling by the oncologist to their patients. Oncologists can motivate patients to receive the correct vaccine schedule by addressing doubts and concerns about the potential negative impact of the vaccine on cancer and cancer therapies., (© 2024. The Author(s).)

Background: In patients with cancer, lean body mass loss is frequent and associated with worse outcomes, including reduced treatment tolerance and survival. Bioelectrical impedance analysis (BIA) is a popular method for body composition assessment. We evaluated the value of BIA-derived body composition parameters in predicting mortality and, for the first time, dose-limiting toxicity (DLT)., Patients and Methods: We conducted a prospective multicenter (n = 12) observational study in adult patients with solid neoplastic disease and receiving primary systemic treatment. We collected information on BIA-derived parameters: phase angle (PhA) <5th percentile of age and gender-specific normative values; standardized PhA (SPA) <-1.65; Nutrigram® <660 mg/24 h/m and <510 mg/24 h/m for males and females, respectively. The primary outcome and the key secondary were 1-year mortality and DLT (any-type severe toxicity requiring a delay in systemic treatment administration or a reduction of its dosage), respectively., Results: In total, 640 patients were included. At 12 months, death occurred in 286 patients (47.6%). All BIA-derived body composition parameters were independently associated with death: SPA, hazard ratio (HR) = 1.59 [95% confidence interval (CI) 1.30-1.95] (P < 0.001); PhA, HR = 1.38 (95% CI 1.13-1.69) (P = 0.002); Nutrigram®, HR = 1.71 (95% CI 1.42-2.04) (P < 0.001). DLT occurred in 208 patients (32.5%) and body composition parameters were associated with this outcome, particularly SPA: odds ratio = 6.37 (95% CI 2.33-17.44) (P < 0.001)., Conclusions: The study confirmed that BIA-derived body composition parameters are independently associated not only with survival but also with DLT. Although our findings were limited to patients receiving first-line systemic treatment, the evidence reported may have important practice implications for the improvement of the clinical work-up of cancer patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The most studied anticancer restrictive diets include fasting, fasting-mimicking diets (FMDs) and ketogenic diets (KDs). Besides the current lack of established clinical benefit and the significant risk of malnutrition and micronutrient deficiencies, dietary restrictions in cancer patients might have relevant psychological effects., Materials and Methods: We reviewed the randomized and non-randomized controlled clinical trials (CCTs) reporting data on the psychological impact of fasting, FMDs and KDs in cancer patients. We excluded trials on restrictive diets performed for weight reduction in obese or overweight patients, studies on dietary restrictions lasting less than 24 h, and studies on fasting related to cultural or religious beliefs., Results: Three CCTs on fasting or FMDs and eight CCTs on KDs in cancer patients were included. In terms of diet-related distress, emotional, social, and family well-being, none of these studies showed a detrimental impact of fasting, FMDs and KDs. However, clinical trials specifically assessing the psychological aspects in the long term are lacking., Conclusions and Perspectives: In the absence of a conclusive evidence on the clinical benefits of restrictive diets, which carry significant risks especially if unsupervised, further studies are needed to clarify their psychological impact in cancer patients. Multidisciplinary approaches including psychological evaluations should be used to ameliorate patient selection for clinical trials, identify early distress symptoms, and increase patient compliance to dietary recommendations., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Despite advances in their diagnosis and treatment, pediatric cancers remain among the leading causes of death in childhood. The development of immunotherapies and other forms of targeted therapies has significantly changed the prognosis of some previously incurable cancers in the adult population. However, so far, the results in pediatric cohorts are disappointing, which is mainly due to differences in tumor biology, including extreme heterogeneity and a generally low tumor mutational burden. A central role in the limited efficacy of immunotherapeutic approaches is played by the peculiar characteristics of the tumor microenvironment (TME) in pediatric cancer, with the scarcity of tumor infiltration by T cells and the abundance of stromal cells endowed with lymphocyte suppressor and tumor-growth-promoting activity. Thus, progress in the treatment of pediatric solid tumors will likely be influenced by the ability to modify the TME while delivering novel, more effective therapeutic agents. In this review, we will describe the TME composition in pediatric solid tumors and illustrate recent advances in treatment for the modulation of immune cells belonging to the TME.

Objectives: To date, studies have not provided definitive answers regarding whether previous immune checkpoint inhibitor (ICI) treatment alters outcomes for cancer patients with COVID-19., Methods: The OnCovid registry (NCT04393974) was searched from February 27, 2020, to January 31, 2022, for patients who received systemic anti-cancer therapy in the 4 weeks before laboratory-confirmed COVID-19 diagnosis. Propensity-score matching using country, vaccination status, primary tumor type, sex, age, comorbidity burden, tumor stage, and remission status investigated differences in predefined clinical outcomes comparing those who had or had not received ICIs., Results: Of 3523 patients screened, 137 ICI-only and 1378 non-ICI met inclusion criteria. Before matching, ICI patients were older, male, enrolled at centers in Italy, and had histories of smoking, thoracic cancers, advanced cancer stages, and active malignancies (P ≤0.02). After matching, there were 120 ICI and 322 non-ICI patients. ICI patients had no differences (odds ratio: 95% CI) in presenting COVID-19 symptoms (0.69: 0.37-1.28), receipt of COVID-specific therapy (0.88: 0.54-1.41), 14-day (0.95: 0.56-1.61), or 28-day (0.79: 0.48-1.29) mortalities. However, ICI patients required less COVID-19-related hospitalization (0.37: 0.21-0.67) and oxygen therapy (0.51: 0.31-0.83) and developed fewer complications (0.57: 0.36-0.92)., Conclusion: In this propensity-score matched analysis, previous ICI therapy did not worsen and potentially improved COVID-19 outcomes in patients with cancer., Competing Interests: Declarations of competing interest Alessio Cortellini received consulting fees from MSD, BMS, AstraZeneca, Roche; and speakers’ fees from AstraZeneca, MSD, Novartis, and Eisai. Matteo Lambertini acted as a consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, and Seagen and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen and Sandoz outside the submitted work. Alessandra Gennari has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, Eisai, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds: Eisai, Eli Lilly, and Roche. CMV has received travel grants and other honoraria from BMS, MSD, Novartis, and Roche. Joan Brunet has declared consulting/advisory role for MSD and Astra Zenec, and support for attending meetings and/or travel for GSK. Josep Tabernero reports personal financial interest in the form of scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics and TheraMyc. Stocks: Oniria Therapeutics and also educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource (PER). Lorenza Rimassa reports receiving consulting fees from AstraZeneca, Basilea, Bayer, BMS, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; lecture fees from AstraZeneca, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi, Servier; travel expenses from AstraZeneca; and institutional research funding from Agios, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks. David J Pinato received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, Eisai, Falk Foundation, travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, Eisai, Roche, DaVolterra, and Astra Zeneca; research funding (to institution) from MSD and BMS. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Herpes zoster (HZ) is caused by the reactivation of latent varicella zoster virus (VZV). Severe immunocompromising conditions, such as solid tumors, have been largely associated with an increased risk for HZ due to waning VZV-specific cellular immunity. With the approval of the adjuvanted glycoprotein E (gE)-based recombinant vaccine (RZV; Shingrix™, GSK) also in immunocompromised subjects, HZ is considered a vaccine-preventable disease changing perspectives in immunocompromised subjects. To date, no clinical trial has evaluated the immunogenicity in the patients with cancer undergoing immunotherapy. In this study, we describe the humoral and cell-mediated immune responses in 38 cancer patients treated with immune checkpoint inhibitors (ICIs) and receiving RZV. We used samples collected at baseline (T0), 3 weeks (T2), and 6 months (T3) after the complete RV vaccination schedule. Our data showed that a significant proportion (40,5%) of RZV recipients mounted a stronger humoral and cell-mediated immune response at 3 weeks (T2) after complete RZV vaccination schedule. Interestingly, both humoral and cell-mediated immune responses were mostly stable over 6 months (T3). Interestingly, the overall IFNγ-producing lymphocytes was mainly associated with CD4 T cell response ( p  = .0012). In conclusion, data from our pilot study suggest a strong and long-lasting immunogenicity of RZV in ICI-treated patients. Prospective analyses at 1 year after vaccination will be performed in order to evaluate the long-term persistence of humoral and cell-mediated response against RZV.

Throughout their experience of illness and during the course of treatment, a substantial proportion of cancer patients are prone to develop nutritional and/or metabolic disturbances. Additionally, cancer patients often encounter long-term side effects from therapies, which may lead to impaired digestion, nutrient absorption or bowel motility. Therefore, the preservation and maintenance of an optimal and balanced nutritional status are pivotal to achieving a better prognosis, increasing the tolerance and adherence to cancer therapies and improving the overall quality of life. In this context, personalized nutritional programs are essential for addressing conditions predisposing to weight loss, feeding difficulties, digestion problems and intestinal irregularity, with the goal of promoting adequate nutrient absorption and minimizing the detrimental effects of treatment regimens. The focus of this research is to examine the most common clinical conditions and metabolic changes that cancer patients may experience, including stomatitis, xerostomia, diarrhea, nausea, vomiting, dysphagia, sub-occlusion, dysgeusia, dysosmia, anorexia, and cachexia. Furthermore, we present a pragmatic example of a multidisciplinary workflow that incorporates customized recipes tailored to individual clinical scenarios, all while maintaining the hedonic value of the meals.

Introduction: The gut microbiota (GM) can influence the pathogenesis of immune-mediated adverse events (irAEs). Proton pump inhibitors (PPIs) can affect the integrity of GM, but their role in promoting irAEs is still poorly understood., Methods: In this retrospective single-center cohort study, the primary endpoint was the evaluation of the incidence of gastrointestinal (GI) irAEs in cancer patients on PPIs (exposed) versus cancer patients who were not on PPIs (unexposed)., Results: Three hundred and sixty three patients' records (248 M/115F, median age 69) were reviewed. Twenty-three exposed patients (92%) developed GI irAEs while only two unexposed patients (8%) developed GI irAEs (hazard ratio [HR] 13.22, 95% confidence interval [CI] 3.11-56.10, p < 0.000). This HR was confirmed after weighting for the propensity score (HR15.13 95% CI 3.22-71.03, p < 0.000)., Conclusion: Chronic PPI use is associated with an increased risk of GI irAES., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Malnutrition is a frequent problem in oncology and is associated with reduced response to cancer treatments, increased drug-related toxicity, higher rates of clinical complications, reduced quality of life (QoL) and worse prognosis. Guidelines on clinical nutrition in oncology emphasise the usefulness of early assessment of nutritional status for a prompt identification of malnutrition and the implementation of effective interventions, but no real-world clinical data are available on the adequate management of nutritional support in patients with cancer in Italy., Methods and Analysis: This is an observational, longitudinal, multicentre registry of patients with a new diagnosis of cancer or metastatic disease, candidates for active treatment. They will be identified in at least 15 Italian oncological centres, members of the Alliance Against Cancer Working Group 'Survivorship Care and Nutritional Support'. At least 1500 patients with cancer are expected to be enrolled each year. Detailed clinical and nutritional data will be collected by oncologists and clinical nutritionists during the visits foreseen in the clinical practice, through an ad hoc developed digital platform (e-Nutracare). The effects of malnutrition and nutritional support-at diagnosis and during follow-up-on overall survival and progression-free survival, as well as on patients' symptoms and QoL, will be investigated., Ethics and Dissemination: The study protocol was approved by the Ethics Committee of the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy and from the Ethics Committees of all other participating centres. An informed consent will be obtained from each patient enrolled in the study. Study findings will be disseminated through peer-reviewed journals, conferences and patients with cancer or professional associations. The registry will allow a better monitoring of the nutritional status of patients with cancer, promoting adequate and sustainable nutritional support, with the ultimate goal of improving the care and prognosis of these patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with the reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS-STING (cyclic GMP-AMP synthase-signalling adaptor stimulator of interferon genes)-dependent cytosolic DNA response gene program. This mechanically driven transcriptional rewiring ultimately alters the cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemoresistance in invasive breast carcinoma., (© 2022. The Author(s).)

The role and durability of the immunogenicity of the BNT162b2 mRNA vaccine against severe acute respiratory virus 2 (SARS-CoV-2), in cancer patients one year after receiving the third dose have to be elucidated. We have prospectively evaluated the long-term immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in 55 patients undergoing active treatment. Neutralizing antibody (NT Ab) titers against Omicron variants and total anti-trimeric S IgG levels were measured one year after the third dose. Heparinized whole-blood samples were used for the assessment of the SARS-CoV-2 interferon-γ release assay (IGRA). Thirty-seven patients (67.3%) showed positive total anti-trimeric S IgG one year after the third dose. Looking at the T-cell response against the spike protein, the frequency of responder patients did not decrease significantly between six and twelve months after the third dose. Finally, less than 20% of cancer patients showed an undetectable NT Ab titer against BA.1 and BA.5 variants of concern (VOCs). Underlying therapies seem to not affect the magnitude or frequency of the immune response. Our work underlines the persistence of humoral and cellular immune responses against BNT162b2 in a cohort of cancer patients one year after receiving the third dose, regardless of the type of underlying therapy.

Background: COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2., Methods: OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)-delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974., Findings: At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24-68) from COVID-19 diagnosis, were included (964 [50·7%] of 1902 patients with sex data were female and 938 [49·3%] were male). Overall, 317 (16·6%; 95% CI 14·8-18·5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the pre-vaccination phase (191 [19·1%; 95% CI 16·4-22·0] of 1000 patients). The prevalence was similar in the alpha-delta phase (110 [16·8%; 13·8-20·3] of 653 patients, p=0·24), but significantly lower in the omicron phase (16 [6·2%; 3·5-10·2] of 256 patients, p<0·0001). In the alpha-delta phase, 84 (18·3%; 95% CI 14·6-22·7) of 458 unvaccinated patients and three (9·4%; 1·9-27·3) of 32 unvaccinated patients in the omicron phase had sequelae. Patients who received a booster and those who received two vaccine doses had a significantly lower prevalence of overall COVID-19 sequelae than unvaccinated or partially vaccinated patients (ten [7·4%; 95% CI 3·5-13·5] of 136 boosted patients, 18 [9·8%; 5·8-15·5] of 183 patients who had two vaccine doses vs 277 [18·5%; 16·5-20·9] of 1489 unvaccinated patients, p=0·0001), respiratory sequelae (six [4·4%; 1·6-9·6], 11 [6·0%; 3·0-10·7] vs 148 [9·9%; 8·4-11·6], p=0·030), and prolonged fatigue (three [2·2%; 0·1-6·4], ten [5·4%; 2·6-10·0] vs 115 [7·7%; 6·3-9·3], p=0·037)., Interpretation: Unvaccinated patients with cancer remain highly vulnerable to COVID-19 sequelae irrespective of viral strain. This study confirms the role of previous SARS-CoV-2 immunisation as an effective measure to protect patients from COVID-19 sequelae, disruption of therapy, and ensuing mortality., Funding: UK National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust., Competing Interests: Declaration of interests AC has received consulting fees from MSD, Bristol Myers Squibb, AstraZeneca, and Roche, and speakers' fee from AstraZeneca, MSD, Novartis, and Eisai. ML acted as a consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, and Seagen, and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen, and Sandoz outside the submitted work. AG declares consulting or advisory roles for Roche, MSD, Eli Lilly, Pierre Fabre, Eisai, and Daichii Sankyo; speakers' fees for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, AstraZeneca, Celgene, and Daichii Sankyo; and research funds from Eisai, Eli Lilly, and Roche. CM-V has received travel grants and other honoraria from Bristol Myers Squibb, MSD, Novartis, and Roche. JB has declared consulting or advisory roles for MSD and AstraZeneca, and support for attending meetings and travel from GlaxoSmithKline. OM reports personal fees from Grupo Pacifico, Kyowa Kirin, Roche, and ROVI, and travel support from Almirall, Kyowa Kirin, and Sanofi. JT reports personal financial interest in the form of scientific consultancy roles for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, and TheraMyc; stocks in Oniria Therapeutics; and educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource. LRi reports receiving consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Bristol Myers Squibb, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Servier, Taiho Oncology, and Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi, and Servier; travel expenses from AstraZeneca; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, and Zymeworks. AD'A has received educational support for congress attendance and consultancy fees from Roche. DJP has received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, Eisai, and the Falk Foundation; travel expenses from Bristol Myers Squibb and Bayer Healthcare; consulting fees for Mina Therapeutics, Eisai, Roche, DaVolterra, and Astra Zeneca; and institutional research funding from MSD and Bristol Myers Squibb. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer., Methods: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19., Findings: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR 30 ) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR 30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR 30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 10 9  cells/L, p=0.0098)., Conclusion: Anti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2., Competing Interests: Competing interests: KJH declares research funding from AstraZeneca, Boehringer-Ingelheim, MSD, Replimune and advisory board fees/honoraria from Arch Oncology, AstraZeneca, BMS, Boehringer-Ingelheim, Codiak Biosciences, Inzen Therapeutics, Merck-Serono, MSD, Pfizer, Replimune. DA reports consultation/advisory role for AstraZeneca, Bristol Myers Squibb, Merck Sharp reports speaker’s engagement from AstraZeneca, Bristol Myers Squibb, Merck Sharp reports serving as local PI for Bristol Myers Squibb, Pierre Fabre Pharma and coordinating PI for OncoLytics; reports grant funding from AbbVie; reports being/been DSMB chair of Sanofi (Genzyme); reports being/been a steering committee member of Roche. Olivier Michielin reports personal fees from Bristol-Myers Squibb, MSD, Novartis, Roche, Amgen, NeraCare, outside the submitted work. JR received speaker or advisory fees from Roche, Astra Zeneca, Merck, Ferrer, Persan Farma, Teva Pharma, Leo Pharma, Fresenius kabi, MSD, BMS. Travel expenses support from BMS, MSD, RocheUrania Dafni reports honorarium as Member of the Tumor Agnostic Evidence Generation Working Group of Roche, outside the submitted work. GP reports grants from Amgen, Lilly; grants, personal fees and nonfinancial support from Merck; grants and non-financial support from AstraZeneca; grants and personal fees from Roche, Bristol Myers Squibb, MSD, Novartis, outside the submitted work. Solange Peters reports consultation/advisory role for AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol- Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody; talk in a company’s organized public event for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda; receipt of grants/research supports from being a (sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. Emanuela Rromano reports investigator-initiated trial (funds paid to the institution) supported by Astra-Zeneca, BMS; serves on the consultancy/advisory board for Astra-Zeneca, Merck, Roche, Pierre Fabre. ML acted as consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, Seagen and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen and Sandoz outside the submitted work.Alessandra Gennari has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds: EISAI, Eli Lilly, and Roche. CMV has received travel grants and other honoraria from BMS, MSD, Novartis and Roche. Joan Brunet has declared consulting/advisory role for MSD and Astra Zeneca. Aleix Prat has declared personal honoraria from Pfizer, Roche, MSD Oncology, Eli Lilly, and Daiichi Sankyo; travel, accommodations, and expenses paid by Daiichi Sankyo; research funding from Roche and Novartis; and consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb. Mark Bower received speakers’ fee from EISAI pharma, Gilead Sciences, Merck and ViiV. JT reports consulting fees from Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Scandion Oncology, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, and TheraMyc; speaker’s fees from Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource; and institutional research support from Amgen, Array Biopharma, AstraZeneca Pharmaceuticals, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma International, Janssen-Cilag, MedImmune, Menarini, Merck Health, Merck Sharp and has had leadership roles in the European AIDS Clinical Society, UNAIDS, WHO, and The European Hematology Association/ European Society of Medical Oncology. DJP received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, EISAI, Falk Foundation, travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, DaVolterra and Astra Zeneca; research funding (to institution) from MSD and BMS. AC received consulting fees from MSD, BMS, AstraZeneca, Roche; speakers’ fee from AstraZeneca, MSD, Novartis and Eisai. All remaining authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: The role and the durability of the immunogenicity of the third dose of vaccine against COVID-19 variants of concern in cancer patients have to be elucidated., Patients and Methods: We have prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 messenger RNA vaccine in triggering both humoral and cell-mediated immune response in patients with solid tumors undergoing active treatment 6 months after the booster. Neutralizing antibody (NT Ab) titers and total anti-spike immunoglobulin G concentrations were measured in serum. Heparinized whole blood samples were used for the SARS-CoV-2 interferon-γ release assay (IGRA)., Results: Six months after the third dose only two patients (2.4%) showed negative spike-specific immunoglobulin G antibody levels (<33.8 BAU/ml). The median level of SARS-CoV-2 NT Abs decreased and only 39/83 (47%) subjects showed maximum levels of NT Abs. T-cellular positive response was observed in 38/61 (62.3%) patients; the highest median level of response was observed 21 days after the third dose (354 mIU/ml, interquartile range 83.3-846.3 mIU/ml). The lowest median level of NT Ab response was observed against the Omicron variant (1 : 10, interquartile range 1 : 10-1 : 40) with a significant reduced rate of responder subjects with respect to the wild-type strain (77.5% versus 95%; P = 0.0022) and Delta variant (77.5% versus 93.7%; P = 0.0053). During the follow-up period, seven patients (8%) had a confirmed post-vaccination infection, but none of them required hospitalization or oxygen therapy., Conclusions: Our work highlights a significant humoral and cellular immune response among patients with solid tumors 6 months after the third BNT162b2 vaccine dose, although a reduction in neutralizing activity against Omicron was observed., Competing Interests: Disclosure The authors have declared no conflicts of interest. Authorship All authors contributed to the article and approved the submitted version., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Iron supplementation improves the erythropoiesis-stimulating agents' (ESAs) response in chemotherapy-related anemia. The primary aim of our study is to assess the efficacy of sucrosomial iron, a new oral iron formulation, in cancer patients with chemotherapy-induced anemia treated with ESAs. The secondary objectives included the efficacy into two subgroups of patients (iron replete and functional iron deficiency) between the two study arms, safety and the effect on transfusion need., Methods: In this randomized, multicentre, open-label, phase III clinical trial, 60 cancer patients were enrolled. Each patient was randomly assigned (1:1) to receive 12 weeks of oral sucrosomial iron at the dose of 30 mg daily in combination with ESAs or no supplementation to ESA treatment. The endpoint considered for efficacy was the proportion of patients achieving complete hematological response at 12 weeks (increase in Hb > 2 g/dL from baseline, without RBC transfusions in the previous 28 days or achieving Hb ≥ 12 g/dL)., Results: There was a statistically significant association between oral sucrosomial iron supplementation in combination with ESAs and the achievement of a complete hematological response. This response was achieved within 12 weeks by 31% of patients in the control group and by 52% of patients supplemented with oral sucrosomial iron. A trend of greater response in sucrosomial iron arm was found in both subgroups. No difference was observed about safety and transfusion need., Conclusions: Sucrosomial iron is well tolerated and its combination with ESAs improves the hematological response in cancer patients with chemotherapy-related anemia., Trial Registration Number and Date of Registration: This study has been reviewed by the Institutional Ethics Committee of the IRCCS Policlinico San Matteo Foundation, Pavia, Italy (28/04/2015; prot. N. 20,150,002,059), and by the Institutional Ethics Committee of the other Italian oncological centers involved in this study., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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

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.)

Purpose: Nutritional support is a keystone component in perioperative care in patients undergoing oncological surgery with a direct impact on surgical outcomes. This study aimed to evaluate how nutritional support in the surgical setting is managed and applied in Italian hospitals., Methods: A national survey was designed by the Italian Society of Surgical Oncology (SICO) and disseminated in early 2021. The results were analyzed for the entire population and for comparing the following different subgroups: northern vs. southern regions; high-volume vs. low-volume centers; and junior vs. senior surgeons., Results: Out of the 141 responses collected from all Italian regions, 43.2% of the participants worked in a surgical unit where nutritional status evaluations and interventions were not routinely practiced, although the key features (nutritional counseling, oral supplementation, enteral and parenteral nutrition) were available in 77.3% of the hospitals. Among the participating centers, the ERAS protocol was systematically applied in only 29.5% of cases, and in 25.5% of cases, most of the items were followed, although not systematically. Among the surgeons who practiced in compliance with the ERAS pathways, almost half of the participants declared that the protocol was applied only for low-risk patients. No significant differences were documented when comparing Italian regions, high-volume vs. low-volume institutions or junior vs. senior participants., Conclusion: Nutritional support in oncological surgery is frequently neglected in Italian hospitals, regardless of the geographic distribution and volumes of the institutions. A cultural change and an improvement in the availability of nutritional services are needed for widespread implementation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests or conflicts of interest related to this article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The omicron (B.1.1.529) variant of SARS-CoV-2 is highly transmissible and escapes vaccine-induced immunity. We aimed to describe outcomes due to COVID-19 during the omicron outbreak compared with the prevaccination period and alpha (B.1.1.7) and delta (B.1.617.2) waves in patients with cancer in Europe., Methods: In this retrospective analysis of the multicentre OnCovid Registry study, we recruited patients aged 18 years or older with laboratory-confirmed diagnosis of SARS-CoV-2, who had a history of solid or haematological malignancy that was either active or in remission. Patient were recruited from 37 oncology centres from UK, Italy, Spain, France, Belgium, and Germany. Participants were followed up from COVID-19 diagnosis until death or loss to follow-up, while being treated as per standard of care. For this analysis, we excluded data from centres that did not actively enter new data after March 1, 2021 (in France, Germany, and Belgium). We compared measures of COVID-19 morbidity, which were complications from COVID-19, hospitalisation due to COVID-19, and requirement of supplemental oxygen and COVID-19-specific therapies, and COVID-19 mortality across three time periods designated as the prevaccination (Feb 27 to Nov 30, 2020), alpha-delta (Dec 1, 2020, to Dec 14, 2021), and omicron (Dec 15, 2021, to Jan 31, 2022) phases. We assessed all-cause case-fatality rates at 14 days and 28 days after diagnosis of COVID-19 overall and in unvaccinated and fully vaccinated patients and in those who received a booster dose, after adjusting for country of origin, sex, age, comorbidities, tumour type, stage, and status, and receipt of systemic anti-cancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974, and is ongoing., Findings: As of Feb 4, 2022 (database lock), the registry included 3820 patients who had been diagnosed with COVID-19 between Feb 27, 2020, and Jan 31, 2022. 3473 patients were eligible for inclusion (1640 [47·4%] were women and 1822 [52·6%] were men, with a median age of 68 years [IQR 57-77]). 2033 (58·5%) of 3473 were diagnosed during the prevaccination phase, 1075 (31·0%) during the alpha-delta phase, and 365 (10·5%) during the omicron phase. Among patients diagnosed during the omicron phase, 113 (33·3%) of 339 were fully vaccinated and 165 (48·7%) were boosted, whereas among those diagnosed during the alpha-delta phase, 152 (16·6%) of 915 were fully vaccinated and 21 (2·3%) were boosted. Compared with patients diagnosed during the prevaccination period, those who were diagnosed during the omicron phase had lower case-fatality rates at 14 days (adjusted odds ratio [OR] 0·32 [95% CI 0·19-0·61) and 28 days (0·34 [0·16-0·79]), complications due to COVID-19 (0·26 [0·17-0·46]), and hospitalisation due to COVID-19 (0·17 [0·09-0·32]), and had less requirements for COVID-19-specific therapy (0·22 [0·15-0·34]) and oxygen therapy (0·24 [0·14-0·43]) than did those diagnosed during the alpha-delta phase. Unvaccinated patients diagnosed during the omicron phase had similar crude case-fatality rates at 14 days (ten [25%] of 40 patients vs 114 [17%] of 656) and at 28 days (11 [27%] of 40 vs 184 [28%] of 656) and similar rates of hospitalisation due to COVID-19 (18 [43%] of 42 vs 266 [41%] of 652) and complications from COVID-19 (13 [31%] of 42 vs 237 [36%] of 659) as those diagnosed during the alpha-delta phase., Interpretation: Despite time-dependent improvements in outcomes reported in the omicron phase compared with the earlier phases of the pandemic, patients with cancer remain highly susceptible to SARS-CoV-2 if they are not vaccinated against SARS-CoV-2. Our findings support universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19., Funding: National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust., Competing Interests: Declaration of interests DJP has received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, Eisai, and Falk Foundation; travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, Eisai, Roche, DaVolterra, and Astra Zeneca; and research funding (to their institution) from MSD and BMS. MLa has acted as consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, Seagen, and Gilead; and has received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen, Libbs, Knight, and Sandoz. FM has received consulting fees from Eli Lilly, MSD, Takeda, and Roche; and travel support from Sanofi. SP reported that their spouse is employed by AstraZeneca. ASa has received consulting fees from Arqule, Sanofi, and Incyte; speaker's fees from Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Eli Lilly, Sandoz, Eisai, Novartis, Bayer, and MSD; and participation on data monitoring committees for BMS, Servier, Gilead, Pfizer, Eisai, Bayer, and MSD. FG has received consulting fees from Novocure, BMS, PharmaMar, and Novartis; speaker's fees from Novocure; travel support from MSD, Novocure, BMS, Boehringer Ingelheim, PharmaMar, Novartis, and Pierre Fabre; and participation on a data safety monitoring board for MSD, BMS, PharmaMar and Novartis. JH has a leadership role with Blood Cancer UK. NS-G has received speakers' fees from Amgen. GG has received consulting fees or had an advisory role for Janssen, AbbVie, AstraZeneca, Roche, Incyte, and BeiGene, and reported speaker fees from Janssen and AbbVie. LRi has received consulting fees from Taiho Oncology, Servier, Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, and Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, and Sanofi; travel expenses from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, and Zymeworks. JT reports consulting fees from Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Scandion Oncology, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, and TheraMyc; speaker's fees from Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource; and institutional research support from Amgen, Array Biopharma, AstraZeneca Pharmaceuticals, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma International, Janssen-Cilag, MedImmune, Menarini, Merck Health, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA, Spanish Association Against Cancer Scientific Foundation, and Cancer Research UK. MB has received speakers' fee from Eisai pharma, Gilead Sciences, Merck, and ViiV; and has had leadership roles in the European AIDS Clinical Society, UNAIDS, WHO, and The European Hematology Association/ European Society of Medical Oncology. AC has received consulting fees from MSD, BMS, AstraZeneca, and Roche; and speakers' fee from AstraZeneca, MSD, Novartis, and Eisai. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: A significant proportion of patients with cancer who recover from Coronavirus Disease 2019 (COVID-19) may experience COVID-19 sequelae in the early post-infection phase, which negatively affect their continuity of care and oncological outcome. The long-term prevalence and clinical impact of the post-COVID-19 syndrome in patients with cancer are largely unknown., Methods: In this study, we describe the time course of COVID-19 sequelae in patients with non-advanced cancers enrolled in the OnCovid registry., Results: Overall, 186 patients were included, with a median observation period of 9.9 months (95%CI:8,8-11.3) post-COVID-19 resolution. After a median interval of 2.3 months post-COVID-19 (interquartile range: 1.4-3.7), 31 patients (16.6%) reported ≥1 sequelae, including respiratory complications (14, 7.6%), fatigue (13, 7.1%), neuro-cognitive sequelae (7, 3.8%). The vast majority of the patients were not vaccinated prior to COVID-19. COVID-19-related sequelae persisted in 9.8% and 8% of patients 6 and 12 months after COVID-19 resolution. Persistence of sequelae at first oncological follow-up was associated with history of complicated COVID-19 (45.2% vs 24.8%, p = 0.0223), irrespective of oncological features at COVID-19 diagnosis., Conclusion: This study confirms for the first time that, in a largely unvaccinated population, post-COVID-19 syndrome can affect a significant proportion of patients with non-advanced cancer who recovered from the acute illness. COVID-19 sequelae may persist up to 12 months in some patients, highlighting the need for dedicated prevention and supportive strategies., Competing Interests: Conflict of interest statement Alessio Cortellini received consulting fees from MSD, BMS, AstraZeneca, Roche; speakers’ fee from AstraZeneca, MSD, Novartis and Eisai. David J Pinato received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, EISAI, Falk Foundation, travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, DaVolterra and Astra Zeneca; research funding (to institution) from MSD and BMS. Aleix Prat has declared personal honoraria from Pfizer, Roche, MSD Oncology, Eli Lilly, and Daiichi Sankyo; travel, accommodations and expenses paid by Daiichi Sankyo; research funding from Roche and Novartis; and consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb. Matteo Lambertini acted as consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, Seagen and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen and Sandoz outside the submitted work. Thomas Newsom-Davis has declared consulting/advisory role for Amgen, Bayer, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Roche, and Takeda; speakers fees from AstraZeneca, MSD, Roche, Takeda and travel, accommodations and expenses paid by AstraZenca, BMS, Boehringer Ingelheim, Lilly, MSD, Otsuka, Roche, and Takeda. Joan Brunet has declared consulting/advisory role for MSD and Astra Zeneca. Alessandra Gennari has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds: EISAI, Eli Lilly, and Roche. CMV has received travel grants and other honoraria from BMS, MSD, Novartis and Roche. Gianluca Gaidano has declared consulting/advisory role for Janssen, Abbvie, Astra-Zeneca and BeiGene, and speaker fees from Janssen and Abbvie. Lorenza Rimassa received consulting fees from Servier, Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi; travel expenses from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks. All remaining authors have declared no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Tweetable abstract Herpes zoster (HZ) is a vaccine-preventable disease, but the role of the vaccine in cancer patients during immunotherapy (ICIs) is still unknown. The clinical and economic consequences of HZ and the increased use of ICIs require a greater awareness by the oncologist.

Background: Although a full course of coronavirus disease 2019 (COVID-19) vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 messenger RNA vaccine in cancer patients undergoing active treatment., Patients and Methods: Patients with solid cancer, vaccinated with a booster dose during active treatment, were enrolled in this study. Patients were classified into SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Ab) titer and total anti-Spike immunoglobulin G (IgG) concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline and 3 weeks after the booster., Results: One hundred and forty-two consecutive patients were recruited. In SARS-CoV-2-naïve subjects, the median level of IgG was 157 BAU/ml [interquartile range (IQR) 62-423 BAU/ml] at T0 and reached a median of 2080 BAU/ml (IQR 2080-2080 BAU/ml) at 3 weeks after booster administration (T1; P < 0.0001). A median 16-fold increase of SARS-CoV-2 NT Ab titer (IQR 4-32) was observed in naïve subjects (from median 20, IQR 10-40, to median 640, IQR 160-640; P < 0.0001). Median interferon-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2-naïve subjects (P = 0.0049) but not in SARS-CoV-2-experienced patients. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to the wild-type strain (P = 0.0004) and 12-fold lower compared to the Delta strain (P = 0.0110)., Conclusions: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern seem to confirm the lower vaccine activity., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine., Patients and Methods: In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/10 6 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy., Results: The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/10 6 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively)., Conclusions: Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Importance: Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined., Objective: To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic., Design, Setting, and Participants: OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer., Exposures: SARS-CoV-2 infection., Main Outcomes and Measures: Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021)., Results: At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years ; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020; 12.5% (95% CI, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021 (all P < .001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; P = .03), have at least 2 comorbidities (793 of 1626 [48.8%] vs 427 of 1008 [42.4%]; P = .001), and have advanced tumors (708 of 1626 [46.4%] vs 536 of 1008 [56.1%]; P < .001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%] vs 342 of 1008 [33.9%]; P < .001) and require hospitalization (969 of 1626 [59.8%] vs 418 of 1008 [42.1%]; P < .001) and anti-COVID-19 therapy (1004 of 1626 [61.7%] vs 501 of 1008 [49.7%]; P < .001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; P < .001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, anti-COVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak., Conclusions and Relevance: The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time.

Background: Low muscle strength has been pointed out as a key characteristic of sarcopenia, but the prognostic significance of muscle function next to reduced skeletal muscle mass (SMM) in patients with cancer has been scantily investigated., Methods: Data on muscle strength by handgrip (HG) dynamometry and total-body SMM estimated by bioelectrical impedance analysis (BIA) of Italian and German patients with cancer observed prospectively until death or censoring were analysed (N = 1076). Patients were stratified in four risk categories based on low HG (<10th percentiles of age and gender-specific normative values) and low total-body SMM according to SMM index cutoffs (<10.75 and <6.75 kg/m 2 in men and women, respectively)., Results: During a median follow-up of 58 months [25th-75th percentile, 37-60], 566 patients had died. Patients presenting low HG in combination or not with low SMM were characterised by shorter median survival (12.7 vs. 27.2 months, respectively; p < 0.001) compared to those with low SMM/normal HG and normal SMM/normal HG (>60 months for both). After adjusting for sex, age, body mass index and percentage of weight loss, disease's stage, performance status and type of cancer, compared to reference category (normal HG and SMM; N = 210) the hazard ratios were: low SMM/normal HG (N = 342), 0.83 [95% confidence interval, CI, 0.67-1.02] (p = 0.073); normal SMM/low HG (N = 158), 1.19 [95% CI, 1.07-1.32] (p = 0.002); low SMM/low HG (N = 366), 1.39 [95% CI, 1.27-1.53] (p < 0.001)., Conclusions: Muscle weakness was found to be a more powerful predictor of survival than BIA-estimated SMM and should be considered as an additional key feature of sarcopenia in patients with cancer., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection., Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients' death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974., Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4-57·8) from cancer diagnosis and 44 days (28-329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p<0·0001), complicated COVID-19 (p<0·0001), and COVID-19 therapy (p=0·0002). With a median post-COVID-19 follow-up of 128 days (95% CI 113-148), COVID-19 sequelae were associated with an increased risk of death (hazard ratio [HR] 1·80 [95% CI 1·18-2·75]) after adjusting for time to post-COVID-19 reassessment, sex, age, comorbidity burden, tumour characteristics, anticancer therapy, and COVID-19 severity. Among 466 patients on systemic anti-cancer therapy, 70 (15·0%) permanently discontinued therapy, and 178 (38·2%) resumed treatment with a dose or regimen adjustment. Permanent treatment discontinuations were independently associated with an increased risk of death (HR 3·53 [95% CI 1·45-8·59]), but dose or regimen adjustments were not (0·84 [0·35-2·02])., Interpretation: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely affect survival and oncological outcomes after recovery. Adjustments to systemic anti-cancer therapy can be safely pursued in treatment-eligible patients., Funding: National Institute for Health Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust., Competing Interests: Declaration of interests DJP reports lecture fees from ViiV Healthcare, Bayer Healthcare, Bristol Myers Squibb, Roche, Eisai, and Falk Foundation; travel expenses from Bristol Myers Squibb and Bayer Healthcare; consulting fees from Mina Therapeutics, Eisai, Roche, DaVolterra, and Astra Zeneca; and research funding (to institution) from Merck Sharp and Dohme and Bristol Myers Squibb, outside of the submitted work. MLa acted as consultant for Roche, Novartis, Lilly, and AstraZeneca, outside of the submitted work, and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, and Sandoz, outside of the submitted work. EF reports research funding to institution from Pfizer, outside of the submitted work, and travel expenses from Lilly, Novartis, Pfizer, and Esai, outside of the submitted work. TN-D reports consulting fees from Amgen, Bayer, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novartis, Otsuka, Pfizer, Roche, and Takeda, outside of the submitted work; speakers fees from AstraZeneca, Merck Sharp and Dohme, Roche, and Takeda, outside of the submitted work; and travel, accommodation, and expenses from AstraZenca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck Sharp and Dohme, Otsuka, Roche, and Takeda, outside of the submitted work. JB reports consulting fees for Merck Sharp and Dohme and Astra Zeneca, outside of the submitted work. APr reports personal honoraria from Pfizer, Roche, Merck Sharp and Dohme Oncology, Eli Lilly, and Daiichi Sankyo, outside of the submitted work; travel, accommodations, and expenses by Daiichi Sankyo, outside of the submitted work; research funding (to institution) from Roche and Novartis, outside of the submitted work; and consulting fees from NanoString Technologies, Amgen, Roche, Novartis, Pfizer, and Bristol-Myers Squibb, outside of the submitted work. APar reports consulting fees from Takeda and Novartis, outside of the submitted work. MT reports travel grants from Roche, Bristol-Myers Squibb, AstraZeneca, and Takeda, outside of the submitted work; and honoraria as a medical writer from Novartis and Amgen, outside the submitted work. AG reports consulting fees from Roche, Merck Sharp and Dohme, Eli Lilly, Pierre Fabre, Eisai, and Daichii Sankyo, outside the submitted work; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, AstraZeneca, Celgene, and Daichii Sankyo, outside the submitted work; research funds (to institution) from Eisai, Eli Lilly, and Roche, outside the submitted work; support for attending meetings or travel from Bristol-Myers Squibb, Merck Sharp and Dohme, Novartis, and Roche, outside the submitted work; and personal research funding from Associazione Italiana per la Ricerca sul Cancro Foundation UPO aging project, outside the submitted work. GG reports personal research funding outside of the submitted work from Associazione Italiana per la Ricerca sul Cancro Foundation, outside the submitted work; consulting fees from Janssen, Abbvie, AstraZeneca, and BeiGene, outside the submitted work; and speaker fees from Janssen and Abbvie, outside the submitted work. LR reports consulting fees from Servier, Amgen, ArQule, AstraZeneca, Basilea, Bayer, Bristol Myers Squibb, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, Merck Sharp and Dohme, Nerviano Medical Sciences, Roche, Sanofi, and Zymeworks, outside the submitted work; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, and Sanofi, outside the submitted work; travel expenses from Ipsen, outside the submitted work; and institutional research funding (to institution) from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, Merck Sharp and Dohme, Nerviano Medical Sciences, Roche, and Zymeworks, outside the submitted work. JT reports having a scientific consultancy role for Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, Merck Sharp and Dohme, Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, and TheraMyc, outside of the submitted work; educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource, outside of the submitted work; and institutional financial interest in form of financial support for clinical trials or contracted research for Amgen, Array Biopharma, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma International, Janssen-Cilag, MedImmune, Menarini, Merck Healt, Merck Sharp and Dohme, Merus, Mirati, Novartis Farmacéutica, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho, Spanish Association Against Cancer Scientific Foundation, and Cancer Research UK, outside the submitted work. ACo reports consulting fees from Merck Sharp and Dohme, Bristol Myers Squibb, AstraZeneca, and Roche, outside the submitted work; and speaker fees from AstraZeneca, Merck Sharp and Dohme, Novartis, and Astellas, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Malnutrition is a frequent comorbidity in people with cancer, associated with poor tolerance of anticancer treatments, prognosis, and quality of life. Despite the abundance of scientific literature supporting this evidence and the availability of international guidelines for managing nutritional care in people with cancer, attitudes about this issue still vary considerably among oncologists, to the point that many patients who are malnourished do not receive adequate nutritional support. In view of this, the Italian Association of Medical Oncology, the Italian Society of Artificial Nutrition and Metabolism, and the Italian Federation of Volunteer-based Cancer Organizations implemented in 2016 a collaborative working group and initiated a structured project called Integrating Nutritional Therapy in Oncology, with the aim of increasing oncologists' awareness of nutritional issues and consequently improving the nutritional care of cancer patients in Italy. In 2019, the Italian Society of Oncological Surgery and the Technical Scientific Association of Food, Nutrition and Dietetics joined the working group. In this article, we present the updated initiatives and the perspectives of this intersociety project., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Tumor-associated vessels constitution is the result of angiogenesis, the hallmark of cancer essential for tumor to develop in dimension and to spread throughout the organism. Tumor endothelium is configured as an active functioning organ capable of determine interaction with the immune response and all the other components of the variegate cancer microenvironment, determining reciprocal influence. Angiogenesis is here analyzed in its molecular and cellular mechanisms, multiple mediators and principal players, represented by Endothelial Cells. It is discussed the striking heterogeneity of cancer endothelium, due to morphological and molecular aberrations that it often presents and its multiple origin. Among the cells that participate to the composition of tumor vasculature, Endothelial Progenitor Cells represent an important source for physical sustain and paracrine signaling in the process of angiogenesis. Treatment options are reviewed, with particular focus on novel therapeutic strategies for overcoming tumor resistance to anti-angiogenic agents., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: There are several case reports suggesting that G-CSFs may, in rare conditions, produce serious side effects, such as vasculitis. Materials & methods: A systematic search was conducted in Medline via PubMed, Embase and Cochrane Library to describe this unusual side effect to raise awareness among clinicians for early recognition and treatment. Results: Fifty-seven patients were analyzed. The most prevalent cancer type was breast cancer (47%). Long-acting G-CSF was used in 38 patients (67%). Only 47% of patients were treated with steroids. Conclusion: Although the benefit of G-CSF treatment outweighs the potential damage, oncologists should consider the possibility of triggering a vascular toxicity and try to identify patients at increased risk for this side effect.

Background: Very few cancer patients were enrolled in coronavirus disease-2019 vaccine studies. In order to address this gap of knowledge, real-world studies are mandatory. The aim of this study was to assess both humoral and cellular response after a messenger RNA vaccination schedule., Patients and Methods: Eighty-eight consecutive cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors were enrolled from the beginning of the vaccination campaign for frail patients. Blood samples for humoral and cell-mediated immune response evaluation were obtained before vaccination (T0), before the second administration (T1) and 21 days after the second dose (T2). The primary endpoint was the evaluation of the percentage of participants showing a significant increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells, measured by an enzyme-linked immunospot assay, after the second dose of BNT162b2 vaccine. The proportion of patients who reached the primary endpoint is computed together with its exact binomial 95% confidence interval., Results: In SARS-CoV-2-naïve subjects, spike-specific T-cell response was almost undetectable at T0 [median 0.0 interferon-γ (IFN-γ) spot forming units (SFU)/million peripheral blood mononuclear cell (PBMC) interquartile range (IQR) 0-7.5] and significantly increased at T1 and T2 (median 15.0 IFN-γ SFU/million PBMC, 25th-75th 0-40 versus 90 IFN-γ SFU/million PBMC, 25th-75th 32.5-224, respectively) (P < 0.001). Focusing on naïve and experienced SARS-CoV-2 subjects, no differences were reported both in terms of CD4- and CD8-specific T-cell response, suggesting that BNT162b2 is able to elicit both adaptive responses after complete vaccination schedule, regardless of previous SARS-CoV-2 exposure. The level of SARS-CoV-2 neutralizing antibodies was low at T1 in SARS-CoV-2-naïve subjects [median 1 : 5 (IQR 1 : 5-1 : 20)] but reached a significantly higher median of 1 : 80 (25th-75th 1 : 20-1 : 160) at T2 (P < 0.0001). Moreover, no COVID-19 cases were documented throughout the period of study., Conclusions: Our data have demonstrated that the administration of a full course of BNT162b2 vaccine elicited a sustained immune response against SARS-CoV-2 regardless of the type of cancer and/or the type of immune checkpoint inhibitors., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Reduced muscle mass represents one of the top ranked phenotypic criteria for malnutrition proposed by the Global Leadership Initiative on Malnutrition. Although height-indexed fat-free mass (FFMI) thresholds have been proposed as useful surrogate measures of reduced muscle mass, the independent prognostic value of BIA-derived FFMI by bioelectric impedance analysis (BIA) in patients with cancer still needs to be fully explored., Methods: Data on body mass index (BMI), 6-month percentage of weight loss (%WL), FFMI by BIA and quality of life (QoL by EORTC Quality of Life Questionnaire [EORTC QLQ-C30]) of Italian and German patients observed prospectively until death or censoring were used (N = 1217). Patients were stratified in 5 risk categories according to a robustly validated scoring system based on BMI and %WL. Low FFMI was defined as follows: men, <17 kg/m 2 ; women, <15 kg/m 2 ., Results: Reduced FFMI was found in 234 patients (19.2%). After a median follow-up of 57 months [25th-75th, 31-60], 620 patients (50.9%) had died. The study detected differences in survival between patients presenting with and without reduced FFMI (14.0 months vs. 45.1 months; P < 0.001). The fully-adjusted hazard ratio of mortality for low FFMI was 1.46 [95%CI, 1.18-1.81] (P < 0.001). Low FFMI was also independently associated with reduced QoL: fully-adjusted odds ratio, 1.50 [95%CI, 1.00-2.25] (P = 0.050)., Conclusions: Reduced FFMI by BIA independently predicted survival and was associated with impaired QoL. Altered body composition should always be considered in all patients with cancer as additional phenotypic criterion of poor prognosis and BIA offers the possibility of multiple, noninvasive bedside assessments., Competing Interests: Conflict of interest All Authors certify that there are no affiliations with or involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Estimation errors associated with bioelectric impedance evaluation may affect the accuracy of body composition and its prognostic value. We evaluated the prognostic value of a new body composition parameter (Nutrigram®) obtained from bioimpedance vectorial analysis-derived body cell mass and its association with nutritional and functional status., Design: Data of Italian and German cancer patients observed prospectively until death were used. Multivariable models (adjusted for age, gender, hydration status, performance status, and disease's stage) were built in both cohorts to assess the association between body composition outcome parameters (low fat-free mass [FFM], <15 [females] and <17 [males] kg/m 2 ; low standardized phase angle [SPA], <-1.65; low Nutrigram®, <510 [females] and <660 [males] mg/24 h/m) and 1-year all-cause mortality, low body mass index (BMI; <20 [<70 years] and <22 [≥70 years] kg/m 2 ), clinically significant weight loss (WL; ≥10% in 6 months) and low handgrip strength (HG; <20 [females] and <30 [males] kg)., Results: Low Nutrigram® was independently associated with mortality in both Italian (HR = 1.84 [95%CI, 1.18-2.86]; P = 0.007) and German cohorts (HR = 1.52 [95%CI, 1.17-2.07]; P = 0.008). Low FFMI and low SPA did not predict survival in the German cohort. In patients with low Nutrigram®, worse nutritional and functional status were observed in both study populations. Performance of models addressing the study endpoints showed substantial consistency with both cohorts, particularly of those including low Nutrigram®., Conclusions: We validated a new prognostic body composition parameter, which is easier to interpret than standard nutritional parameters and may be useful for identifying cancer patients at nutritional risk, requiring early nutritional support., Competing Interests: Conflict of interest All Authors certify that there are no affiliations with or involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Attitudes toward cancer-related malnutrition vary considerably among oncologists and nutritional support is often not handled according to the available guidelines. The Italian Association of Medical Oncology (AIOM), Italian Society of Artificial Nutrition and Metabolism (SINPE), Italian Federation of Volunteer-based Cancer Organizations (FAVO), and Fondazione AIOM Working Group conducted a national web-based survey addressed to all Italian Oncology Units referees and Italian Cancer Patients Associations. The aim was to investigate the current management of malnutrition and views on nutritional care among oncologists and patients. One hundred and seventy-one (51.6%) of the 331 registered Italian Oncology Units and 75 (38.5%) of the 195 FAVO local communities participated in the survey. Nutritional assessment and support were integrated into patient care from diagnosis for 35% of Oncology Unit referees and 15% of FAVO associates. According to 42% of oncologists, nutritional assessment was carried out only after patients requested it, while it was not performed at all for 45% of FAVO associates. Almost 60% of patient affiliates were not aware of clinical referrals for home artificial nutrition management. However, for almost all responders, the evaluation of nutritional status was considered crucial in predicting tolerance to anticancer treatment. Although malnutrition was considered a limiting factor in oncology treatments by both oncologists and patients, nutritional care practices still appear largely inappropriate. Attitudes differ between oncologists and patients, the latter reporting a more dissatisfied picture. Improving nutritional care in oncology remains a challenging task., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The COVID-19 outbreak has drastically changed practices inside hospitals, which include oncology routines. In oncology, malnutrition was and certainly still is a frequent problem associated with an increase in treatment-related toxicity, a reduced response to cancer treatment, an impaired quality of life, and a worse overall prognosis. Even in this situation of healthcare crisis, nutritional support in cancer care is an essential element. During the current COVID-19 pandemic, there is a concrete high risk to see a dramatic worsening of cancer patients' nutritional status, who are left without adequate clinical and nutritional support. The consequences are already reasonably foreseeable and will have a severe negative impact after the emergency. Therefore, we believe that it is essential to try to continue, as far as possible, the activity of clinical nutrition in oncology, by revolutionizing the setting and the approach to patients. For this purpose, the Clinical Nutrition and Dietetics Unit and the Medical Oncology Unit of our hospital, one of the largest community hospital in Lombardy that has been involved in the COVID-19 outbreak management since its inception, have reorganized the clinical routine activity in strict collaboration since the very beginning of the emergency, to better face up to the challenge, while preserving cancer patients' needs.

State-of-the-art treatment strategies have drastically ameliorated the outcome of patients affected by cancer. However, resistant and recurrent solid tumors are generally nonresponsive to conventional therapies. A central factor in the sequence of events that lead to cancer is an alteration in antitumor immune surveillance, which results in failure to recognize and eliminate the transformed tumor cell. A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of cancer provides the basis for improved therapies. Targeted strategies, such as T-cell therapy, not only generally spare normal tissues, but also use alternative antineoplastic mechanisms that synergize with other therapeutics. Despite encouraging success in hematologic malignancies, adaptive cellular therapies for solid tumors face unique challenges because of the immunosuppressive tumor microenvironment, and the hurdle of T-cell trafficking within scarcely accessible tumor sites. This review provides a brief overview of current cellular therapeutic strategies for solid tumors, research carried out to increase efficacy and safety, and results from ongoing clinical trials., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In recent years, whey proteins (WP) have attracted increasing attention in health and disease for their bioactive functions. The aim of this study was to evaluate the benefit of WP isolate (WPI) supplementation in addition to nutritional counseling in malnourished advanced cancer patients undergoing chemotherapy (CT). In a single-center, randomized, pragmatic, and parallel-group controlled trial (ClinicalTrials.gov: NCT02065726), 166 malnourished advanced cancer patients with mixed tumor entities candidate to or undergoing CT were randomly assigned to receive nutritional counseling with (N = 82) or without (N = 84) WPI supplementation (20 g/d) for 3 months. The primary endpoint was the change in phase angle (PhA). Secondary endpoints included changes in standardized PhA (SPA), fat-free mass index (FFMI), body weight, muscle strength, and CT toxicity (CTCAE 4.0 events). In patients with the primary endpoint assessed (modified intention-to-treat population), counseling plus WPI (N = 66) resulted in improved PhA compared to nutritional counseling alone (N = 69): mean difference, 0.48° (95% CI, 0.05 to 0.90) (P = .027). WPI supplementation also resulted in improved SPA (P = .021), FFMI (P = .041), body weight (P = .023), muscle strength (P < .001), and in a reduced risk of CT toxicity (risk difference, -9.8% [95% CI, -16.9 to -2.6]; P = .009), particularly of severe (grade ≥ 3) events (risk difference, -30.4% [95% CI, -44.4 to -16.5]; P = .001). In malnourished advanced cancer patients undergoing CT, receiving nutritional counseling, a 3-month supplementation with WPI resulted in improved body composition, muscle strength, body weight, and reduced CT toxicity. Further trials, aimed at verifying the efficacy of this nutritional intervention on mid- and long-term primary clinical endpoints in newly diagnosed specific cancer types, are warranted., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The increasing availability of novel biological anticancer agents has greatly improved the outcome of several cancer patients; unfortunately, data regarding efficacy, safety and pharmacokinetics of many of these agents in patients with chronic renal disease or on hemodialysis are scanty. Furthermore these results are controversial and a treatment strategy has not yet been established. Therefore, the Associazione Italiana di Oncologia Medica and the Società italiana di Nefrologia undertook the present work aiming at providing health professionals with a tool for easier clinical management of target therapies in this setting of patients. A web-based search of MEDLINE/PubMed library data published from 2000 to June 2018 has been performed. More than one hundred papers, including recommendations and expert opinions, were selected and discussed by the authors. A panel of experts provided additional biological and clinical information, helping in clarifying some issues in the absence of clear-cut information from the literature., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The international guidelines recommend the use of supplemental parenteral nutrition (SPN) in cancer patients when they are malnourished and hypophagic and where enteral nutrition is not feasible. However, there are limited data on the short-term effects of SPN in this patient population., Methods: The aim of this bicentric single-arm clinical trial (NCT02828150) was to evaluate the effects of early 7-day SPN on bioimpedance vectorial analysis (BIVA)-derived body composition, handgrip strength (HG), and serum prealbumin (PAB) in 131 hypophagic, hospitalized cancer patients at nutritional risk, with contraindications for enteral nutrition., Results: One hundred eighteen patients (90.1%) completed the 7-day SPN support regimen and 102 of them (86.4%) were in advanced disease stage. SPN induced a significant improvement of phase angle (PhA, + 0.25 [95% CI 0.11, 0.39]; p = 0.001), standardized phase angle (SPA, + 0.33 [95% CI 0.13, 0.53]; p = 0.002), HG (+ 2.1 kg -95% CI 1.30, 2.81]; p < 0.001), and PAB (+ 3.8 mg/dL [95% CI 2.1, 5.6]; p < 0.001). In multivariable analysis, the effects on BIVA parameters were more pronounced in patients (N = 90, 76.3%) in whom estimated protein and calorie requirements were both satisfied (adjusted difference: PhA, + 0.39 [95% CI 0.04, 0.73]; p = 0.030; SPA, + 0.62 [95% CI 0.16, 1.09]; p = 0.009). No significant changes in hydration status were detected and no severe metabolic or other complications occurred., Conclusions: Early 7-day SPN resulted in improved body composition, HG and PAB levels in hypophagic, and hospitalized cancer patients at nutritional risk in the absence of any relevant clinical complications. Further trials, aimed at verifying the efficacy of this early nutritional intervention on mid- and long-term primary clinical endpoints in specific cancer types, are warranted.