A significant proportion of patients treated for early breast cancer develop medium-term and late distant recurrence. The delayed manifestation of metastatic disease is defined as “dormancy”. This model describes the aspects of the clinical latency of isolated metastatic cancer cells. Dormancy is regulated by extremely complex interactions between disseminated cancer cells and the microenvironment where they reside, the latter in turn influenced directly by the host. Among these entangled mechanisms, inflammation and immunity may play leading roles. This review is divided into two parts: the first describes the biological underpinnings of cancer dormancy and the role of the immune response, in particular, for breast cancer; the second provides an overview of the host-related factors that may influence systemic inflammation and immune response, subsequently impacting the dynamics of breast cancer dormancy. The aim of this review is to provide physicians and medical oncologists a useful tool to understand the clinical implications of this relevant topic.
Osimertinib represents the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) mutations, constituting 80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted. The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression-free survival (mPFS), and overall survival were estimated by the Kaplan-Meier method. Eighty-six patients harboring uEGFR and treated with osimertinib were identified. Patients with 'major' uEGFR, that is, G719X, L861X, and S768I mutations (n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer 'minor' mutations (n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation (n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Amplification of EGFR or MET, TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy. The ARTICUNO study confirms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon-common mutations, or major uEGFR, even in the presence of BMs. Alterations at the E709 residue of EGFR are associated with resistance to osimertinib.
In recent years, awareness regarding micro-nanoplastics’ (MNPs) potential effects on human health has progressively increased. Despite a large body of evidence regarding the origin and distribution of MNPs in the environment, their impact on human health remains to be determined. In this context, there is a major need to address their potential carcinogenic risks, since MNPs could hypothetically mediate direct and indirect carcinogenic effects, the latter mediated by particle-linked chemical carcinogens. Currently, evidence in this field is scarce and heterogeneous, but the reported increased incidence of malignant tumors among younger populations, together with the ubiquitous environmental abundance of MNPs, are rising a global concern regarding the possible role of MNPs in the development and progression of cancer. In this review, we provide an overview of the currently available evidence in eco-toxicology, as well as methods for the identification and characterization of environmental MNP particulates and their health-associated risks, with a focus on cancer. In addition, we suggest possible routes for future research in order to unravel the carcinogenetic potential of MNP exposure and to understand prognostic and preventive implications of intratumoral MNPs.
15 December 2023 in International Journal of Cancer
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.
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.
Ralstonia spp. are low-virulent environmental Gram-negative bacteria that can cause serious nosocomial infections in immunocompromised patients. We report the characteristics of a cluster of R. insidiosa bacteremia cases occurring in our oncology day ward in Milan, Italy, between January and March 2022. A case was defined as a cancer patient attending our day ward and whose blood culture (performed because of bacteremia symptoms) led to the isolation of Ralstonia insidiosa. An epidemiological investigation was conducted in order to seek the possible source of infection. Seven adult patients received curative or palliative treatment via infusion through a Port-a-Cath (PAC). All developed symptoms within 24 h of the infusion (three during the infusion itself). Ralstonia insidiosa was isolated in the blood drawn from the PAC in all patients. All of the isolates were susceptible to carbapenems, fluoroquinolones, and piperacillin/tazobactam but resistant to aminoglycosides and cephalosporins. Systemic and/or lock antibiotic therapy led to stable symptom resolution and negative blood cultures in five patients, whereas bacteremia recurred in two patients. An epidemiological investigation suggested that extrinsic contamination of antiseptic solutions was the possible cause of the R. insidiosa infections. Although R. insidiosa is not considered a virulent pathogen, clinicians, microbiologists, and infection control teams should be aware about its potential to cause outbreaks of nosocomial bloodstream infections, especially in immunocompromised patients bearing central venous catheters.