A Subset of PD-1-Expressing CD56bright NK Cells Identifies Patients with Good Response to Immune Checkpoint Inhibitors in Lung Cancer.

(1) Despite the effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer, there is a lack of knowledge about predictive biomarkers. The objective of our study is to analyze different subsets of T-lymphocytes and natural killer (NK) cells as predictive biomarkers in a cohort of patients with nonsmall cell lung cancer (NSCLC) treated with ICI. (2) This is an observational, prospective study with 55 NSCLC patients treated with ICI. A total of 43 T and NK cell subsets are analyzed in peripheral blood, including the main markers of exhaustion, differentiation, memory, activation, and inhibition. (3) Regarding the descriptive data, Granzyme B+CD4+ Treg lymphocytes stand out (median 17.4%), and within the NK populations, most patients presented cytotoxic NK cells (CD56+CD3-CD16+GranzymeB+; median 94.8%), and about half of them have highly differentiated adaptive-like NK cells (CD56+CD3-CD16+CD57+ (mean 59.8%). A statistically significant difference was observed between the expression of PD1 within the CD56bright NK cell subpopulation (CD56+CD3-CD16-PD-1+) (p = 0.047) and a better OS. (4) Circulating immune cell subpopulations are promising prognostic biomarkers for ICI. Pending on validation with a larger sample, here we provide an analysis of the major circulating T and NK cell subsets involved in cancer immunity, with promising results despite a small sample size.

Diagnosis of Malnutrition According to GLIM Criteria Predicts Complications and 6-Month Survival in Cancer Outpatients.

Background and Aims: Malnutrition is a condition that has a great impact on oncology patients. Poor nutritional status is often associated with increased morbidity and mortality, increased toxicity, and reduced tolerance to chemotherapy, among other complications. The recently developed GLIM criteria for malnutrition aim to homogenize its diagnosis, considering the baseline disease status. We aimed to evaluate the performance of these new criteria for the prediction of complications and mortality in patients with cancer. Methods: This work is a prospective, single-center study. All outpatients under active treatment for head and neck, upper gastrointestinal, and colorectal tumors between February and October 2020 were recruited. These patients were followed up for 6 months, assessing the occurrence of complications and survival based on GLIM diagnoses of malnutrition. Results: We enrolled 165 outpatients, 46.66% of whom were malnourished. During the 6-month follow-ups, patients with malnutrition (46.7%, according to GLIM criteria) had a ~3-fold increased risk of hospital admission (p < 0.001) and occurrence of severe infection (considered as those requiring hospitalization, intravenous antibiotics, and/or drainage by interventional procedures) (p = 0.002). Similarly, malnourished patients had a 3.5-fold increased risk of poor pain control and a 4.4-fold increased need for higher doses of opioids (both p < 0.001). They also had a 2.6-fold increased risk of toxicity (p = 0.044) and a 2.5-fold increased likelihood of needing a dose decrease or discontinuation of cancer treatment (p = 0.011). The 6-month survival of malnourished patients was significantly lower (p = 0.023) than in non-malnourished patients. Conclusions: Diagnoses of malnutrition according to the GLIM criteria in oncology patients undergoing active treatment predict increased complications and worse survival at 6-month follow-ups, making them a useful tool for assessing the nutritional status of oncology patients.

Comparation of different malnutrition screening tools according to GLIM criteria in cancer outpatients.

BACKGROUND: Many studies have assessed different malnutrition screening tools in oncologic patients. However, very few have been carried out using the new GLIM criteria for malnutrition. The objective of our study is to compare the most recommended screening tools with respect to the new GLIM criteria for malnutrition in cancer patients. METHODS: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department at the Lozano Blesa Hospital in Zaragoza. We recruited 165 patients with tumors of the upper-gastrointestinal-tract, colorectal, and head-and-neck region undergoing outpatient treatment. All of them received MST, MUST, Nutriscore, MNA and CONUT screening tools, as well as the GLIM diagnostic criteria, which was used as the gold standard. RESULTS: MNA-SF showed the best sensitivity (0.99) and lowest specificity while CONUT had the best specificity (0.89) and lowest sensitivity to detect cancer-related malnutrition. We observed high variability in the diagnostic capabilities of Nutriscore when tumor location was considered, reducing sensitivity in patients with colorectal cancer compared to those with tumors of the upper-gastrointestinal-tract or head-and-neck location (0.25, 0.83, and 0.91 respectively). The highest index of agreement between the screening tools was found between MST, MUST and Nutriscore tests. Regarding the GLIM criteria, the highest agreement index was presented by MUST tool (0.66), while CONUT presented the lowest (0.12). CONCLUSIONS: Selecting the screening tool according to the type of cancer and its location may allow us to optimize its use and increase its performance, exploiting the advantages of each of them in the different populations.

GLIM vs ESPEN criteria for the diagnosis of early malnutrition in oncological outpatients.

BACKGROUND & AIMS: Malnutrition is one of the most prevalent problems among oncological patients. It reduces the response to treatments and negatively impacts survival. In 2019, a consensus criteria for diagnosing malnutrition (GLIM criteria) were proposed by most scientific nutrition societies. The objective of our work is 1) to assess the diagnostic capacity of the GLIM criteria in ambulatory patients with cancer and 2) to compare the GLIM with the ESPEN criteria to evaluate the contributions of these new criteria with respect to the existing ones. METHODS: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department in the Lozano Blesa Clinical Hospital in Zaragoza (Spain). One hundred and sixty-five outpatients with tumors in the upper gastrointestinal tract, head and neck, and colorectal locations were recruited. All of them received the MST, MUST, and Nutriscore screening tools along with the ESPEN and GLIM diagnostic criteria. RESULTS: The prevalence of malnutrition was 46.7% according to the GLIM criteria and 21.2% using the ESPEN tool. Patients diagnosed by GLIM had a higher body mass index (BMI, 24.3 kg/m2) and muscle mass (MM, 16.1 kg/m2) than those diagnosed by ESPEN (21.2 kg/m2 and 14.3 kg/m2 respectively, both p = 0.001). The MST, MUST, and Nutriscore tools had a higher degree of concordance with GLIM compared to ESPEN (MST 0.53 vs 0.26; MUST 0.36 vs 0.66; Nutriscore 0.28 vs 0.54). CONCLUSIONS: The found prevalence of malnutrition in cancer patients is higher using the GLIM instead of ESPEN criteria. This disparity can be explained at least in part by the difficulty of the ESPEN criteria for malnutrition to diagnose patients with high baseline BMI or MM. The use of criteria with greater sensitivity, such as the new GLIM criteria, could help early diagnosis and thus early intervention in cancer patients.

Acute Polyneuropathy in an Outpatient Context During the SARS-CoV-2 Pandemic: A Brief Case Serie Report.

Guillain-Barré syndrome (GBS) is a well-established complication of infectious disease. So it is not surprising that several cases have been described during the actual SARS-CoV-2 infection pandemic. Most of the descriptions are patients suffering a severe GBS in the setting of a severe SARS-CoV-2 infection. We described five patients with mild forms of COVID-19. After 2-4 weeks, these patients develop mild neurological symptoms. The clinical and neurophysiological studies supported a diagnosis of an acute polyneuropathy. Symptoms resolved without specific treatment and primary care physicians managed all patients outpatiently. Mild SARS-CoV-2 infection could associate mild neurological complications too. So patients complaining about mild neurological symptoms, a SARS-CoV-2 infection may be excluded. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42399-021-00855-x.

How Could Antibiotics, Probiotics, and Corticoids Modify Microbiota and Its Influence in Cancer Immune Checkpoint Inhibitors: A Review.

Immunotherapy has become a new paradigm in oncology, improving outcomes for several types of cancer. However, there are some aspects about its management that remain uncertain. One of the key points that needs better understanding is the interaction between immunotherapy and gut microbiome and how modulation of the microbiome might modify the efficacy of immunotherapy. Consequently, the negative impact of systemic antibiotics and corticosteroids on the efficacy of immunotherapy needs to be clarified.

From Tumor Mutational Burden to Blood T Cell Receptor: Looking for the Best Predictive Biomarker in Lung Cancer Treated with Immunotherapy.

Despite therapeutic advances, lung cancer (LC) is one of the leading causes of cancer morbidity and mortality worldwide. Recently, the treatment of advanced LC has experienced important changes in survival benefit due to immune checkpoint inhibitors (ICIs). However, overall response rates (ORR) remain low in unselected patients and a large proportion of patients undergo disease progression in the first weeks of treatment. Therefore, there is a need of biomarkers to identify patients who will benefit from ICIs. The programmed cell death ligand 1 (PD-L1) expression has been the first biomarker developed. However, its use as a robust predictive biomarker has been limited due to the variability of techniques used, with different antibodies and thresholds. In this context, tumor mutational burden (TMB) has emerged as an additional powerful biomarker based on the observation of successful response to ICIs in solid tumors with high TMB. TMB can be defined as the total number of nonsynonymous mutations per DNA megabases being a mechanism generating neoantigens conditioning the tumor immunogenicity and response to ICIs. However, the latest data provide conflicting results regarding its role as a biomarker. Moreover, considering the results of the recent data, the use of peripheral blood T cell receptor (TCR) repertoire could be a new predictive biomarker. This review summarises recent findings describing the clinical utility of TMB and TCRß (TCRB) and concludes that immune, neontigen, and checkpoint targeted variables are required in combination for accurately identifying patients who most likely will benefit of ICIs.

Intratumoral Versus Circulating Lymphoid Cells as Predictive Biomarkers in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Is the Easiest Path the Best One?

The molecular and cell determinants that modulate immune checkpoint (ICI) efficacy in lung cancer are still not well understood. However, there is a necessity to select those patients that will most benefit from these new treatments. Recent studies suggest the presence and/or the relative balance of specific lymphoid cells in the tumor microenvironment (TEM) including the T cell (activated, memory, and regulatory) and NK cell (CD56dim/bright) subsets, and correlate with a better response to ICI. The analyses of these cell subsets in peripheral blood, as a more accessible and homogeneous sample, might facilitate clinical decisions concerning fast prediction of ICI efficacy. Despite recent studies suggesting that lymphoid circulating cells might correlate with ICI efficacy and toxicity, more analyses and investigation are required to confirm if circulating lymphoid cells are a relevant picture of the lung TME and could be instrumental as ICI response biomarkers. This short review is aimed to discuss the recent advances in this fast-growing field.

Desmoid-Type Fibromatosis: Who, When, and How to Treat.

OPINION STATEMENT: Desmoid-type fibromatosis is a sarcoma subtype that gathers some singular characteristics, making it a difficult challenge to face in clinical practice. Despite its excellent survival prognosis, these tumors may be unpredictable, ranging from an asymptomatic indolent course to persistent, local, and extended recurrences that significantly impair quality of life. Although surgery was initially considered the first elective treatment, collected published data during the past few years are now pointing to the "wait and see" approach as a reasonable initial strategy because many patients can live a long life with the disease without having symptoms. When symptoms appear or there is a risk of functional impairment, a wide spectrum of therapies (local and systemic) can be useful in improving symptoms and controlling the disease. Because of the low incidence of desmoid-type fibromatosis, there is scarce scientific evidence supporting any specific treatment. Nonetheless, if volumetric responses are needed, chemotherapy may be a reasonable early option. However, if long-term control of disease is desirable, hormonal therapy, NSAIDs, and TKIs are the likely treatments of choice. Recent new findings in the biologic development of these tumors, such as the role of Wnt/ß-catenin dependent pathway, have shown that the prognostic information provided by specific CTNNB1 gene mutations and other genetic profiles can lead to better methods of selecting patients as candidates for other approaches. Based on recent research, the Notch pathway inhibition in DF is one of the most promising potential targets to explore. As an orphan disease, it is mandatory that as many patients as possible be included in clinical trials.