The latest and newest discoveries for advanced and metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer are the three cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) in association with endocrine therapy (ET). However, even if this treatment revolutionized the world and continued to be the first-line treatment choice for these patients, it also has its limitations, caused by de novo or acquired drug resistance which leads to inevitable progression after some time. Thus, an understanding of the overview of the targeted therapy which represents the gold therapy for this subtype of cancer is essential. The full potential of CDK4/6i is yet to be known, with many trials ongoing to expand their utility to other breast cancer subtypes, such as early breast cancer, and even to other cancers. Our research establishes the important idea that resistance to combined therapy (CDK4/6i + ET) can be due to resistance to endocrine therapy, to treatment with CDK4/6i, or to both. Individuals’ responses to treatment are based mostly on genetic features and molecular markers, as well as the tumor’s hallmarks; therefore, a future perspective is represented by personalized treatment based on the development of new biomarkers, and strategies to overcome drug resistance to combinations of ET and CDK4/6 inhibitors. The aim of our study was to centralize the mechanisms of resistance, and we believe that our work will have utility for everyone in the medical field who wants to deepen their knowledge about ET + CDK4/6 inhibitors resistance.
COVID-19 reinfection, although a controversial issue, is an important clinical problem in cancer patients and beyond. The present study aimed to identify the risk factors associated with worse outcomes in cancer patients with Covid-19 in both first infection and reinfection and to describe the involvement of vaccines in reinfection outcome. The present study enrolled 85 patients with solid tumors who had Covid-19 infection and had not been previously vaccinated. Classical risk factors associated with worse outcomes in cancer patients with second SARS-Cov infection were considered. The patients were followed up retrospectively, measuring mortality at the first and second infection and the vaccination rate after the first infection. The factors associated with the highest risk of mortality at the first infection were, in order of importance: intensive care unit (ICU) admission, unfavorable performance status, radiologically quantifiable presence of oncological disease, and administration of cytotoxic chemotherapy in the period immediately before infection. The risk factors associated with higher mortality from reinfection were ECOG 3-4 performance status and administration of cytotoxic chemotherapy in the period immediately before infection. In the studied patients, mortality from reinfection was not affected by prior vaccination. Thus, bearing in mind all of these risk factors for poor outcomes in cancer patients with solid tumors presenting with Covid-19 can help the treating oncologists make personalized decisions about patient care during the pandemic.
Background: Metastatic renal cell carcinoma (mRCC) is an aggressive cancer characterised by an increased recurrence rate and an inadequate response to treatment. This study aimed to investigate the importance of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker for long-term survival in patients with mRCC. Methods: We retrospectively analysed data from 74 patients with mRCC treated at our medical centre with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). We evaluated the predictive value of NLR for overall survival (OS) in these patients. Results: The median OS was 5.1 months in the higher NLR group (≥3) and 13.3 months in the lower NLR group (<3) (p < 0.0001). There was no significant difference in the OS between the TKI and ICI therapies in the low NLR group (12.9 vs. 13.6 months, p = 0.411) or in the high NLR group (4.7 vs. 5.5 months, p = 0.32). Both univariate and multivariate analyses revealed that a higher NLR was an independent prognostic factor of long-term survival in patients with mRCC treated with first-line therapy. Conclusions: This retrospective study showed that adding NLR to other Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) variables might improve the prognostic and predictive power of these models.
Lung cancer, as the leading cause of death in oncology is one of the most challenging diseases nowadays. Even after the implementation of checkpoint inhibitors and targeted therapy as a standard of therapy for metastatic disease, the chemotherapy backbone remains essential in the treatment of these patients. This study aimed to evaluate how administration particularities in chemotherapy and toxicity management can influence the outcome. We conducted a retrospective single-institution study, at Elias University Emergency Hospital, Bucharest, Romania, between 2014 and 2018, in a heterogeneous patient population with metastatic non-small cell lung cancer that received combination chemotherapy. The inclusion criteria for this trial were—histological proof of non-small cell lung cancer (NSCLC), stage IV disease, ECOG (Eastern Cooperative Oncology Group) performance status of a maximum of two, treatment with cytotoxic chemotherapy for at least four courses (patients with fewer courses were excluded). All patients received combination chemotherapy. The main focus was on the effect of dose reduction and treatment delay on overall survival and progression-free survival. A total of 129 patients were enrolled. The response rate in the studied population was 69% and 62.8% had no toxicity greater than grade 2. Chemotherapy regimens used had the following distribution—paclitaxel + carboplatin 41.9%, paclitaxel + carboplatin + bevacizumab 12.4%, pemetrexed + carboplatin 12.4%, gemcitabine + carboplatin 26.4% and other regimens 7%. Mean PFS (Progression Free Survival) was 9.1 months and the mean OS (Overall Survival) was 14 months. OS was not significantly different in the treatment delay group versus the no delay one, p < 0.25 but dose- reduction significantly impacted OS, p < 0.03. Administration particularities, like febrile neutropenia prophylaxis, treatment of chemotherapy-related anemia, respecting the details of chemostability and preparation rules and emesis prophylaxis, were considered reasons for the good outcome. Details regarding cytotoxic chemotherapy administration remain of paramount importance for a good outcome and the benefit for survival they convey is crucial. Sometimes the benefit the patient derives from these details is comparable to the one newer therapies convey.
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