Antibody response to three-dose anti-SARS-CoV-2 mRNA-vaccination in treated solid cancer patients.

Solid cancer patients are at higher risk of SARS-CoV-2 infection and severe complications. Moreover, vaccine-induced antibody response is impaired in patients on anticancer treatment. In this retrospective, observational, hypothesis-generating, cohort study, we assessed the antibody response to the third dose of mRNA vaccine in a convenience sample of patients on anticancer treatment, comparing it to that of the primary two-dose cycle. Among 99 patients included, 62.6% were ≥60 years old, 32.3% males, 67.7% with advanced disease. Exactly 40.4% were receiving biological therapy, 16.2% chemotherapy only and 7.1% both treatments. After the third dose, seroconversion rate seems to increase significantly, especially in non-responders to two doses. Heterologous vaccine-type regimen (two-dose mRNA-1273 and subsequent tozinameran or vice versa) results in higher antibody levels. This explorative study suggests that repeated doses of mRNA-vaccines could be associated with a better antibody response in this population. Furthermore, heterologous vaccine-type three-dose vaccination seems more effective in this population. Since this is a hypothesis-generating study, adequately statistically powered studies should validate these results.

Immunogenicity of two doses of BNT162b2 and mRNA-1273 vaccines for solid cancer patients on treatment with or without a previous SARS-CoV-2 infection.

Previous studies on the immunogenicity of SARS-CoV-2 mRNA vaccines showed a reduced seroconversion in cancer patients. The aim of our study is to evaluate the immunogenicity of two doses of mRNA vaccines in solid cancer patients with or without a previous exposure to the virus. This is a single-institution, prospective, nonrandomized study. Patients in active treatment and a control cohort of healthy people received two doses of BNT162b2 (Comirnaty, BioNTech/Pfizer, The United States) or mRNA-1273 (Spikevax, Moderna). Vaccine was administered before starting anticancer therapy or on the first day of the treatment cycle. SARS-CoV-2 antibody levels against S1, RBD (to evaluate vaccine response) and N proteins (to evaluate previous infection) were measured in plasma before the first dose and 30 days after the second one. From January to June 2021, 195 consecutive cancer patients and 20 healthy controls were enrolled. Thirty-one cancer patients had a previous exposure to SARS-CoV-2. Cancer patients previously exposed to the virus had significantly higher median levels of anti-S1 and anti-RBD IgG, compared to healthy controls (P = .0349) and to cancer patients without a previous infection (P < .001). Vaccine type (anti-S1: P < .0001; anti-RBD: P = .0045), comorbidities (anti-S1: P = .0274; anti-RBD: P = .0048) and the use of G-CSF (anti-S1: P = .0151) negatively affected the antibody response. Conversely, previous exposure to SARS-CoV-2 significantly enhanced the response to vaccination (anti-S1: P < .0001; anti-RBD: P = .0026). Vaccine immunogenicity in cancer patients with a previous exposure to SARS-CoV-2 seems comparable to that of healthy subjects. On the other hand, clinical variables of immune frailty negatively affect humoral immune response to vaccination.

Single nucleotide polymorphisms to predict taxanes toxicities and effectiveness in cancer patients.

Taxanes are used in the treatment of several solid tumours. Adverse events (AEs) might be influenced by single nucleotide polymorphisms (SNPs) in genes encoding proteins responsible for pharmacokinetic and pharmacodynamic. In this prospective, monocentric, observational study we explored the effect of SNPs in the main genes involved in taxanes metabolism and transport, on toxicity and efficacy in 125 patients (pts) treated with paclitaxel, nab-paclitaxel, or docetaxel for neoplasms. There was no statistically significant association between the investigated SNPs and AEs. The heterozygous genotype of CYP3A4*22 showed a trend of association with skin reactions in pts treated with paclitaxel and nab-paclitaxel (RR = 6.92; 95% CI 0.47, 99.8; p = 0.0766). CYP2C8*3/*4 variant carriers showed a trend of association with overall AEs in pts treated with paclitaxel and nab-paclitaxel (RR = 1.28; 95% CI 0.96, 1.67; p = 0.0898). No statistically significant relationship with treatment efficacy was found. ABCB1 3435TT showed a trend of association with a higher treatment response (RR = 0.22; 95% CI 0.03, 1.51; p = 0.0876). Despite the population was heterogeneous, CYP3A4*22 and CYP2C8 SNPs may influence paclitaxel and nab-paclitaxel toxicity and ABCB1 c.3435 may affect taxanes effectiveness, even if any statistically significant was found.

Hospital-Based Influenza and Pneumococcal Vaccination for Cancer Patients on Active Treatment and Their Family Members during the COVID-19 Pandemic in Italy: A Single-Center Experience.

In patients with cancer, tumor- and treatment-induced immunosuppression are responsible for a four-fold increase in morbidity and mortality caused by influenza and invasive Streptococcus pneumoniae infections compared to the general population. The main oncology societies strongly recommend vaccination in patients with cancer to prevent these infections. However, vaccine hesitancy is a main concern in this population. The aim of this study was to assess the feasibility of in-hospital vaccination for patients under anticancer treatment and their family members (FMs) against influenza and pneumococcal infections during the COVID-19 pandemic in order to increase vaccine coverage. This was a single-center, prospective, observational study conducted at the Department of Oncology of Luigi Sacco University Hospital (Milan, Italy) between October 2020 and April 2021. The main primary outcome was the incidence of influenza-like illness (ILI) and pneumococcal infections. The main secondary outcome was safety. A total of 341 subjects were enrolled, including 194 patients with cancer and 147 FMs. The incidence of ILI was higher among patients than among FMs (9% vs. 2.7%, OR 3.92, p = 0.02). Moreover, two subjects were diagnosed with pneumococcal pneumonia. The most frequent vaccine-related AEs were pain in the injection site (31%) and fatigue (8.7%). In conclusion, this hospital-based vaccination strategy was feasible during the COVID-19 pandemic, representing a potential model to maximize vaccine coverage during a public health emergency.

Detection and typization of HPV genotypes in subjects with oral and upper respiratory tract lesions, Milan, Italy.

BACKGROUND: Oral human papillomavirus (HPV) is common among healthy individuals but causes and implications of persistent infections are under evaluation in the pathogenesis of head and neck neoplasms. METHODS: This was a retrospective study evaluating the prevalence of high-risk (HR), probable HR and low-risk (LR) HPV types in patients reporting signs/symptoms of oral and upper respiratory tract lesions. Individuals attending between 2019 and 2022 a University Hospital in Milan, Italy, with risk factors for HPV (unprotected oral sex and/or previous documentation of HPV infection in oral and upper respiratory tract and/or another anatomical site) were included. RESULTS: Fourteen out of 110 (12.7%) individuals tested positive for HPV DNA. The prevalence of HR-HPV and LR-HPV was 3.6% (4/110) and 9.1% (10/110), respectively. No probable/possible HR-HPV was detected. Specifically, 10/110 (9.1%) were diagnosed with 1 LR-HPV genotype, 3/110 (2.7%) were infected with 1 HR-HPV and 1/110 had 3 concomitant HR-HPV types. HPV 16 (2.7%, 3/110) and 6 (4.5%, 5/110) were the most common HR and LR types, respectively. One patient positive for HPV 16, 33 and 35 was diagnosed with cancer at the base of the tongue. Two individuals among those who tested positive for HPV DNA reported previous HPV vaccination. CONCLUSIONS: Our data, in line with observations from previous prevalence studies, support the potential role of HPV in head and neck neoplasms. HPV DNA testing should be performed in patients presenting lesions in oral/respiratory tracts and risk factors for HPV. Improvement in HPV vaccination coverage is warranted.

Clinical efficacy of the first two doses of anti-SARS-CoV-2 mRNA vaccines in solid cancer patients.

INTRODUCTION: Cancer patients are frail individuals, thus the prevention of SARS-CoV-2 infection is essential. To date, vaccination is the most effective tool to prevent COVID-19. In a previous study, we evaluated the immunogenicity of two doses of mRNA-based vaccines (BNT162b2 or mRNA-1273) in solid cancer patients. We found that seroconversion rate in cancer patients without a previous exposure to SARS-CoV-2 was lower than in healthy controls (66.7% vs. 95%, p = 0.0020). The present study aimed to evaluate the clinical efficacy of the vaccination in the same population. METHODS: This is a single-institution, prospective observational study. Data were collected through a predefined questionnaire through phone call in the period between the second and third vaccine dose. The primary objective was to describe the clinical efficacy of the vaccination, defined as the percentage of vaccinated subjects who did not develop symptomatic COVID-19 within 6 months after the second dose. The secondary objective was to describe the clinical features of patients who developed COVID-19. RESULTS: From January to June 2021, 195 cancer patients were enrolled. Considering that 7 (3.59%) patients tested positive for SARS-CoV-2 and 5 developed symptomatic disease, the clinical efficacy of the vaccination was 97.4%. COVID-19 disease in most patients was mild and managed at home; only one hospitalization was recorded and no patient required hospitalization in the intensive care unit. DISCUSSION: Our study suggests that increasing vaccination coverage, including booster doses, could improve the prevention of infection, hospitalization, serious illness, and death in the frail population of cancer patients.

Pegylated liposomal doxorubicin as first line treatment in aids-related Kaposi's sarcoma: a real-life study.

Despite the introduction of effective combination antiretroviral therapy (cART) AIDS-related Kaposi Sarcoma (AIDS-KS) remains the most common malignancy in HIV positive patients. In advanced stage or progressive forms, chemotherapy (CT) in combination with cART is the treatment of choice. The aim of the study is to evaluate efficacy and tolerability of Pegylated Liposomal Doxorubicin (PLD) as first line CT in AIDS-KS. In this single institution retrospective study PLD (20 mg/m2 IV every 2 weeks for 6 or 12 cycles) in combination with cART was administered in poor risk and some cases of good prognosis or limited cutaneous disease. Response rate and adverse events to treatment was evaluated. We enrolled 33 patients with AIDS-KS: median age 44ys, male 90.9%, Caucasian 72.7%, cART-naïve (simultaneous diagnosis of HIV infection and KS) 84.4%, median lymphocyte CD4+ count 134cells, median HIV viral load 4.9 log10 copies/ml. 32 patients were assigned to a Poor Risk KS stage. Grade 3-4 toxicity was reported in 9 patients. No cardiovascular events or severe sepsis were described. Complete response was reported in 25 of 31 patients evaluable for efficacy. After a median follow-up of 52 months the 3-years PFS was 68.6%. PLD associated with cART is an effective, feasible and well tolerated first-line CT in advanced AIDS-KS.

ABCB1 c.3435C>T polymorphism is associated with platinum toxicity: a preliminary study.

BACKGROUND: Platinum-based doublets are the standard chemotherapy for lung cancer. The identification of markers associated with drug toxicity may improve the success of the treatment. Single nucleotide polymorphisms (SNPs) mapping into the genes involved in platinum transport or detoxification may explain the occurrence of toxicities. In this study, we evaluated the role of three SNPs in predicting the onset of adverse events for lung cancer patients receiving cisplatin or carboplatin in adjuvant, neo-adjuvant and metastatic settings. METHODS: Eighty-two patients affected by non-small-cell and small-cell lung cancer treated with cisplatin- or carboplatin-based chemotherapy (stage II-IV) were enrolled. Before genetic analysis, patients signed a written informed consent. DNA was extracted from peripheral blood samples and genotypes were determined by real-time PCR. We selected and analyzed three SNPs: ABCB1 c.3435C>T/rs1045642, ABCC2 -24C>T/rs717620 and GSTP1 c.313A>G/rs1695. Patient characteristics and genotypes were correlated with hematological, gastrointestinal and renal toxicity as recorded by Common Terminology Criteria for Adverse Event (CTCAE) v4.03. No neurological toxicity was observed in our patients. RESULTS: Variant alleles were present in 53% of patients for ABCB1 c.3435C >T, 18.3% for ABCC2 -24C> T, and 34.8% for GSTP1 c.313A>G. Heterozygous CT at ABCB1 c.3435 was associated to a lower risk of hematological toxicity compared to homozygous CC (OR = 0.20; 95% CI 0.05, 0.69; p = 0.01). Similar results were observed by genetic dominant model (CT + TT vs CC) and hematological toxicity (OR = 0.26; 95% CI 0.09, 0.79; p = 0.02). No other significant associations were found between toxicity and SNPs. Multivariate analysis confirmed an independent value for the ABCB1 c.3435 C >T polymorphism. CONCLUSIONS: The present study reveals that ABCB1 c.3435C>T polymorphism influences platinum toxicity. The T allele seems to exert a protective effect on the development of toxicities. Further studies, such as epigenetic regulation ones, are needed to validate and shed more light on this association.

A targeted approach to genetic counseling in breast cancer patients: the experience of an Italian local project.

AIMS AND BACKGROUND: Patients with hereditary breast cancer (BC) may benefit from genetic counseling and testing for detection of causative mutations, definition of therapeutic and preventive strategies, and identification of at-risk relatives. Italy has few oncogenetic centers and genetic evaluation of all patients with BC is not feasible. Moreover, lack of uniformity in the selection of patients generates inappropriate referral to the geneticist. We designed a model that may represent a reproducible way to select patients at risk for hereditary BC, with the aims of rationalizing access to genetic centers and improving clinical management and surveillance. METHODS: The genetic unit of a Cancer Center and the Departments of Oncology from 2 public Hospitals in Milan were involved in the project. After training sessions at the genetic unit, operators from the 2 hospitals evaluated all patients with BC attending a first oncologic visit, through a specific interview. Patients considered at risk of hereditary BC attended counseling at the genetic unit. RESULTS: Of 419 patients, 61 (14.5%) were eligible for genetic counseling after the interview. Of these, 46 (10.9%) strictly met testing criteria. Overall, 52 (12.4%) patients underwent genetic counseling and 47 were tested for BRCA1/BRCA2 mutation. After genetic test results, the available options for treatment/surveillance were discussed by a multidisciplinary team, according to the level of genetic risk. CONCLUSIONS: It is possible to improve the process of referring patients with suspected hereditary BC for genetic risk assessment. The application of clinical screening reduced the genetics unit's workload and enabled optimization of time and resources.