Beta-Adrenergic Blockade in Advanced Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Multicentric Study.

Introduction The standard treatment of cancer has dramatically improved with immune checkpoint inhibitors (ICIs). Despite their proven advantage, many patients fail to exhibit a meaningful and lasting response. The beta-adrenergic signalling pathway may hold significant promise due to its role in promoting an immunosuppressive milieu within the tumour microenvironment. Inhibiting ß-adrenergic signalling could enhance ICI activity; however, blocking this pathway for this purpose has yielded conflicting results. The primary objective of this study was to evaluate the effect of beta-blocker use on overall survival and progression-free survival during ICI therapy. Methods A multicentric, retrospective, observational study was conducted in four Portuguese institutions. Patients with advanced non-small cell lung cancer treated with ICIs between January 2018 and December 2019 were included. Those using beta blockers for non-oncological reasons were compared with non-users. Results Among the 171 patients included, 36 concomitantly received beta blockers and ICIs. No significant increase was found in progression-free survival among patients who took ß-blockers (HR 0.74, 95% confidence interval (CI) 0.48-1.12, p = 0.151), and no statistically significant difference was found in overall survival. An apparent trend was observed towards better outcomes in the beta-blocker group, with a median overall survival of 9.93 months in the group not taking ß-blockers versus 14.90 months in the ß-blocker group (p = 0.291) and a median progression-free survival of 5.37 in the group not taking ß-blockers versus 10.87 months in the ß-blocker group (p = 0.151). Nine (25%) patients in the beta-blocker group and 16 (12%) in the non-beta-blocker group were progressive disease-free at the end of follow-up. This difference between the two groups is statistically significant (p = 0.047). Conclusion Our study found no statistically significant evidence that beta blockers enhance the effectiveness of immunotherapy. Using adrenergic blockade to modulate the immune system shows promise, warranting the need to develop prospective clinical studies.

Adipocyte Microenvironment in Ovarian Cancer: A Critical Contributor?

Ovarian cancer is one of the most common gynecological malignancies and has low survival rates. One of the main determinants of this unfavorable prognosis is the high rate of peritoneal metastasis at diagnosis, closely related to its morbidity and mortality. The mechanism underlying peritoneal carcinomatosis is not clearly defined, but a clear preference for omental spread has been described. Growing evidence suggests that adipose tissue plays a role in promoting cancer onset and progression. Moreover, obesity can lead to changes in the original functions of adipocytes, resulting in metabolic and inflammatory changes in the adipose tissue microenvironment, potentially increasing the risk of tumor growth. However, the specific roles of adipocytes in ovarian cancer have not yet been fully elucidated. Due to the undeniable link between obesity and cancer, the adipose tissue microenvironment could also present a promising therapeutic target that warrants further research. This review discusses the complex relationship between ovarian cancer and the adipose tissue microenvironment.

Communication preferences and perceptions of cancer patient during their first medical oncology appointment.

BACKGROUND: The first medical oncology appointment serves as a platform for patients to comprehend their diagnosis and prognostic implications of cancer. This study aimed to determine patients' communication preferences during their first medical oncology appointment and to assess the disparities between patients' preferences and perceptions. METHODS: A total of 169 cancer patients participated by completing the Communication in First Medical Oncology Appointment Questionnaire (C-FAQ), a two-section questionnaire designed to assess patients' preferences and perceptions regarding Content (information provided and its extent), Facilitation (timing and location of information delivery), and Support (emotional support) during their first medical oncology appointment. A comparative analysis was conducted to assess the variations between preferences and perceptions. RESULTS: Content emerged as the most significant dimension compared to Facilitation and Support. The physician's knowledge, honesty, and ability to provide clear information were considered the most important attributes. Patients evaluated most of their preferences as "very important". Patients' perception of the communication dimensions present during their appointment was below preferences for 11 items, indicating significant discrepancies in clinical practice. CONCLUSIONS: Patients highly valued their preferences concerning Content, Facilitation, and Support dimensions of communication. However, patient preferences were more prominently oriented towards the Content dimension. The discrepancies between preferences and perceptions should be viewed as an opportunity for enhancing communication skills through training.

Breast Cancer Survivors and Healthy Women: Could Gut Microbiota Make a Difference?-"BiotaCancerSurvivors": A Case-Control Study.

In this first analysis, samples from 23 BC survivors (group 1) and 291 healthy female controls (group 2) were characterised through the V3 and V4 regions that encode the "16S rRNA" gene of each bacteria. The samples were sequenced by next-generation sequencing (NGS), and the taxonomy was identified by resorting to Kraken2 and improved with Bracken, using a curated database called 'GutHealth_DB'. The α and ß-diversity analyses were used to determine the richness and evenness of the gut microbiota. A non-parametric Mann-Whitney U test was applied to assess differential abundance between both groups. The Firmicutes/Bacteroidetes (F/B) ratio was calculated using a Kruskal-Wallis chi-squared test. The α-diversity was significantly higher in group 1 (p = 0.28 × 10-12 for the Chao index and p = 1.64 × 10-12 for the ACE index). The Shannon index, a marker of richness and evenness, was not statistically different between the two groups (p = 0.72). The microbiota composition was different between the two groups: a null hypothesis was rejected for PERMANOVA (p = 9.99 × 10-5) and Anosim (p = 0.04) and was not rejected for ß-dispersion (p = 0.158), using Unifrac weighted distance. The relative abundance of 14 phyla, 29 classes, 25 orders, 64 families, 116 genera, and 74 species differed significantly between both groups. The F/B ratio was significantly lower in group 1 than in group 2, p < 0.001. Our study allowed us to observe significant taxonomic disparities in the two groups by testing the differences between BC survivors and healthy controls. Additional studies are needed to clarify the involved mechanisms and explore the relationship between microbiota and BC survivorship.

Correction: Association of Tumor-Infiltrating Lymphocytes With Survival in Stages II and III Colorectal Cancer.

[This corrects the article DOI: 10.7759/cureus.31144.].

Association of Tumor-Infiltrating Lymphocytes With Survival in Stages II and III Colorectal Cancer.

The tumor microenvironment is crucial in tumourigenesis, response to therapy, and elimination of tumor cells. Tumor-infiltrating lymphocytes (TILs) promote the host immune response and are associated with a better prognosis in colorectal cancer (CRC). This multicentric retrospective study evaluated the relationship between the presence and intensity of TILs and survival outcomes. A total of 651 patients from four Portuguese oncological centers who underwent surgical resection for stages II or III colorectal adenocarcinoma between 2016 and 2019 were included in this study. The mean age of the study population was 70 years; 58.2% were males. The median overall survival was 58.03 ± 1.29 months (95% confidence interval (CI) 55.50 - 60.56), and the median disease-free survival (DFS) was 53.02 ± 1.39 months (95% CI 50.29 - 55.74). Patients with high infiltrate (including those with moderate, abundant, or Crohn-like infiltrate) had significantly longer DFS i.e., 58.48 ± 1.84 months (95% CI 54.87 - 62.09 months) vs 49.22 ± 1.75 months (95% CI 45.79 - 52.64 months) in the group with absent or minimal infiltrate; p = 0.003. Assessing the side of the tumor, high infiltrate was associated with higher DFS (59.86 ± 2.36 months (95% CI 55.23 - 64.50 months) vs 49.60 ± 2.40 months (95% CI 44.90 - 54.29 months), p = 0.011). This work reinforces the importance of research into possible prognostic and predictive factors in patients with CRC.

Mutation Patterns in Portuguese Families with Hereditary Breast and Ovarian Cancer Syndrome.

Germline pathogenic variants in the Breast Cancer Genes 1 (BRCA1) and 2 (BRCA2) are responsible for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Genetic susceptibility to breast cancer accounts for 5-10% of all cases, phenotypically presenting with characteristics such as an autosomal dominant inheritance pattern, earlier age of onset, bilateral tumours, male breast cancer, and ovarian tumours, among others. BRCA2 pathogenic variant is usually associated with other cancers such as melanoma, prostate, and pancreatic cancers. Many rearrangements of different mutations were found in both genes, with some ethnic groups having higher frequencies of specific mutations due to founder effects. Despite the heterogeneity of germline BRCA1/BRCA2 mutations in Portuguese breast or/and ovarian cancer families, the first described founder mutation in the BRCA2 gene (c.156_157insAlu) and two other variants in the BRCA1 gene (c.3331_3334del and c.2037delinsCC) contribute to about 50% of all pathogenic mutations. Furthermore, the families with the BRCA1 c.3331_3334del or the c.2037delinsCC mutations share a common haplotype, suggesting that these may also be founder mutations in the Portuguese population. Identifying specific and recurrent/founder mutations plays an important role in increasing the efficiency of genetic testing since it allows the use of more specific, cheaper and faster strategies to screen HBOC families. Therefore, this review aims to describe the mutational rearrangements of founder mutations and evaluate their impact on the genetic testing criteria for HBOC families of Portuguese ancestry.

Neutrophile-to-lymphocyte, lymphocyte-to-monocyte, and platelet-to-lymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer.

BACKGROUND: Perioperative fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) improves prognosis in locally advanced gastric cancer (LAGC). Neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte (PLR) ratios are prognostic biomarkers but not predictive factors. AIM: To assess blood ratios' (NLR, LMR and PLR) potential predictive response to FLOT and survival outcomes in resectable LAGC patients. METHODS: This was a multicentric retrospective study investigating the clinical potential of NLR, LMR, and PLR in resectable LAGC patients, treated with at least one preoperative FLOT cycle, from 12 Portuguese hospitals. Means were compared through non-parametric Mann-Whitney tests. Receiver operating characteristic curve analysis defined the cut-off values as: High PLR > 141 for progression and > 144 for mortality; high LMR > 3.56 for T stage regression (TSR). Poisson and Cox regression models the calculated relative risks/hazard ratios, using NLR, pathologic complete response, TSR, and tumor regression grade (TRG) as independent variables, and overall survival (OS) as the dependent variable. RESULTS: This study included 295 patients (mean age, 63.7 years; 59.7% males). NLR was correlated with survival time (r = 0.143, P = 0.014). PLR was associated with systemic progression during FLOT (P = 0.022) and mortality (P = 0.013), with high PLR patients having a 2.2-times higher risk of progression [95% confidence interval (CI): 0.89-5.26] and 1.5-times higher risk of mortality (95%CI: 0.92-2.55). LMR was associated with TSR, and high LMR patients had a 1.4-times higher risk of achieving TSR (95%CI: 1.01-1.99). OS benefit was found with TSR (P = 0.015) and partial/complete TRG (P < 0.001). Patients without TSR and with no evidence of pathological response had 2.1-times (95%CI: 1.14-3.96) and 2.8-times (95%CI: 1.6-5) higher risk of death. CONCLUSION: Higher NLR is correlated with longer survival time. High LMR patients have a higher risk of decreasing T stage, whereas high PLR patients have higher odds of progressing under FLOT and dying. Patients with TSR and a pathological response have better OS and lower risk of dying.

Local Breast Microbiota: A "New" Player on the Block.

The tumour microenvironment (TME) comprises a complex ecosystem of different cell types, including immune cells, cells of the vasculature and lymphatic system, cancer-associated fibroblasts, pericytes, and adipocytes. Cancer proliferation, invasion, metastasis, drug resistance and immune escape are all influenced by the dynamic interaction between cancer cells and TME. Microbes, such as bacteria, fungi, viruses, archaea and protists, found within tumour tissues, constitute the intratumour microbiota, which is tumour type-specific and distinct among patients with different clinical outcomes. Growing evidence reveals a significant relevance of local microbiota in the colon, liver, breast, lung, oral cavity and pancreas carcinogenesis. Moreover, there is a growing interest in the tumour immune microenvironment (TIME) pointed out in several cross-sectional studies on the correlation between microbiota and TME. It is now known that microorganisms have the capacity to change the density and function of anticancer and suppressive immune cells, enabling the promotion of an inflammatory environment. As immunotherapy (such as immune checkpoint inhibitors) is becoming a promising therapy using TIME as a therapeutic target, the analysis and comprehension of local microbiota and its modulating strategies can help improve cancer treatments.

Use of Pembrolizumab in End-Stage Renal Disease: A Case Report with Complete Response.

Second-line treatment in urothelial carcinoma is not well defined. Immunotherapy has shown good outcomes in this setting, but it has not been tested in patients with end-stage renal disease (ESRD). We present a clinical case describing the use of pembrolizumab in a patient under hemodialysis (HD) that achieved a complete response. A 72-year-old man was diagnosed with urothelial carcinoma in 2001. Following transurethral resection of the bladder tumor, bacillus Calmette-Guérin, and mitomycin treatment, he underwent surgery in 2018. The patient required HD since surgery. A few months after surgery, there was disease progression with lung metastasis. A first-line treatment with carboplatin and gemcitabine was started, but after 5 cycles, disease progression was confirmed. It was decided to initiate second-line treatment with pembrolizumab. After 13 months of immunotherapy, a CT scan showed a complete response with total involution of lung metastasis. Immune checkpoint inhibitors are an option to second-line treatment in urothelial carcinoma. Further studies are needed to clarify the efficacy and tolerance of this therapy in ESRD patients.

Basal Cell Adenocarcinoma Arising from the Parotid Gland.

Basal cell adenocarcinoma (BCAC) is a rare malignant tumor of the salivary glands, representing 1-2% of salivary gland neoplasms. It is considered a low-grade tumor, often associated with a good prognosis. We report a case of a 60-year-old man with 3-month history of a growing, painless mass in the right ascending ramus of the mandible. Ultrasound and CT scan showed an asymmetry between parotid glands, depicting a nodular structure on the right side. A parotid fine needle aspiration cytology revealed neoplastic cells suggestive of adenoid cystic carcinoma. The patient underwent a total parotidectomy with lymph node dissection. Histopathology result was reported as BCAC. The patient concluded adjuvant radiotherapy and continued follow-up surveillance without evidence of relapse. The adjuvant approach in this case was decided by a multidisciplinary team given the absence of classically known risk factors. We highlight the importance of considering BCAC in the differential diagnosis in salivary gland tumors.

Uterine Sarcomas: A Retrospective Analysis of a Cohort of 62 Patients.

Background and objective Uterine sarcomas are rare tumors, and they account for 4% of all uterine malignancies. These tumors are characterized by a great diversity of histological types, and current knowledge regarding their treatment is limited. The aim of our study was to analyze a cohort of patients with uterine sarcomas with respect to the histological types of their tumors, as well as their prognosis and treatment. Materials and methods This was a retrospective analysis involving patients diagnosed at a single center with uterine sarcoma between 2003 and 2017.  Results The study included 62 patients; the mean age of the patients was 62 ±13 years. Carcinosarcoma was identified in 44% of cases, leiomyosarcoma in 40%, and endometrial stromal sarcoma in 13%. Endometrial stromal sarcoma was found to occur in younger women compared to carcinosarcoma (52 ±13 vs. 66 ±12 years, p=0.016); 90% of patients underwent surgery, and medical treatment was implemented in 42%. The mean overall survival (OS) was 93 ±10.65 months, and the median progression-free survival (PFS) was 12 months. There was a significant association between the stage of the disease at diagnosis and the probability of survival: mean OS was 118 months for locoregional disease vs. 44 months for metastatic disease (p<0.001). The overall five-year survival rate was 39%. Discussion and conclusions Uterine sarcomas are rare cancers, and they are very heterogeneous. They are also associated with a high mortality rate. Further investigational studies are required so that a more effective treatment method and individualized treatment plans can be implemented for patients with uterine sarcoma.

Human Microbiota and Immunotherapy in Breast Cancer - A Review of Recent Developments.

Breast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Infectious agents are the third most important risk factor for cancer incidence after tobacco and obesity. Dysbiosis emerged as a key player that may influence cancer development, treatment, and prognosis through diverse biological processes. Metastatic BC has a highly variable clinical course, and more recently, immune checkpoint inhibitors (ICIs) have become an emerging therapy in BC. Even with standardised treatment protocols, patients do not respond similarly, reflecting each individual´s heterogeneity, unique BC features, and tumour microenvironment. However, there is insufficient data regarding predictive factors of response to available treatments for BC. The microbiota could be a crucial piece of the puzzle to anticipate better individual BC risk and prognosis, pharmacokinetics, pharmacodynamics, and clinical efficacy. In recent years, it has been shown that gut microbiota may modulate cancer treatments' efficacy and adverse effects, and it is also apparent that both cancer itself and anticancer therapies interact with gut microbiota bidirectionally. Moreover, it has been proposed that certain gut microbes may protect the host against inappropriate inflammation and modulate the immune response. Future clinical research will determine if microbiota may be a prognostic and predictive factor of response to ICI and/or its side effects. Also, modulation of microbiota can be used to improve outcomes in BC patients. In this review, we discuss the potential implications of metabolomics and pharmacomicrobiomics that might impact BC immunotherapy treatment.

Case Report: Pure Red Cell Aplasia due to Angioimmunoblastic T-Cell Lymphoma.

Pure red cell aplasia (PRCA) is a rare bone marrow failure characterized by a progressive normocytic anemia and reticulocytopenia without leukopenia and thrombocytopenia. It can be associated with various hematological disorders but exceedingly rarely with angioimmunoblastic T-cell lymphoma (AITL). We report the case of a 72-year-old woman with PRCA associated with AITL. The patient presented with severe anemia (hemoglobin 2.6 g/dL) and a low reticulocyte count 0.7%. Direct and indirect Coombs tests were positive. A CT scan of the chest, abdomen, and pelvis revealed multiple lymphadenopathies. A cervical lymph node biopsy was compatible with AITL. A bone marrow biopsy showed medullary involvement by AITL and a severe erythroid hypoplasia with a myeloid:erythroid ratio of 19.70. The patient was started on CHOP and after 6 cycles the PET scan confirmed complete remission.